PMID- 2213814 TI - Skin presentation of chronic myelomonocytic leukaemia resembling cutaneous lymphomas. PMID- 2213815 TI - Correlation between serum oncogene protein expression and the development of neoplastic disease in a worker exposed to carcinogens. PMID- 2213816 TI - Communicating information to patients. PMID- 2213817 TI - Pyrimethamine-sulphadoxine: how great the risk? PMID- 2213818 TI - Advanced trauma life support courses. PMID- 2213819 TI - Non-steroidal anti-inflammatory drugs (NSAIDs) and the ileum. PMID- 2213820 TI - Chronic somatizers and the Government White Paper. PMID- 2213821 TI - Antiatherosclerotic agents. A structurally novel bivalent inhibitor of acylCoA:cholesterol O-acyltransferase with systemic activity. PMID- 2213822 TI - Structure-based, C2 symmetric inhibitors of HIV protease. PMID- 2213823 TI - Synthesis and biological activity of 1,2,4-oxadiazole derivatives: highly potent and efficacious agonists for cortical muscarinic receptors. AB - The synthesis and biochemical evaluation of novel 1,2,4-oxadiazole-based muscarinic agonists which can readily penetrate into the CNS is reported. Efficacy and binding of these compounds are markedly influenced by the structure and physicochemical properties of the cationic head group. In a series of azabicyclic ligands efficacy and affinity are influenced by the size of the surface area presented to the receptor, at the active site, and the degree of conformational flexibility. The exo-1-azanorbornane 16a represents the optimum arrangement, and this compound is one of the most efficacious and potent muscarinic agonists known. In a series of isoquinuclidine based muscarinic agonists efficacy and affinity are influenced by the geometry between the cationic head.group and hydrogen bond acceptor pharmacophore and steric bulk in the vicinity of the base. The anti configuration represented by 22a is optimal for muscarinic activity. Ligands with pKa below 6.5 show poor binding to the muscarinic receptor as exemplified by the diazabicyclic derivative 42. PMID- 2213824 TI - Thiazole as a carbonyl bioisostere. A novel class of highly potent and selective 5-HT3 receptor antagonists. AB - A novel structural class of highly potent and selective 5-HT3 receptor antagonists is described. The compounds in this new series contain a thiazole moiety linking an aromatic group and a nitrogen-containing basic region; the thiazole group appears to be acting as a carbonyl bioisostere in this system. An optimized member of this series, 4-(2-methoxyphenyl)-2-[[4(5)-methyl-5(4) imidazolyl]methyl]thiazole (5), exhibits oral activity in the Bezold-Jarisch reflex paradigm comparable to or better than the standard agents ondansetron (1) and ICS-205-930 (2). Several of the structure-activity relationships are rationalized in terms of a computer pharmacophore model for 5-HT3 receptor binding. PMID- 2213825 TI - Torsionally and hydrophobically modified 2,3-diarylindenes as estrogen receptor ligands. AB - 2,3-Diarylindenes are ligands for the estrogen receptor which display intrinsic fluorescence. In order to optimize the receptor binding affinity of these compounds while preserving their desirable fluorescence properties, a series of torsionally modified analogues were prepared. A fluorine or methyl group was introduced on either of the two phenyl substituents ortho to their attachment site to the indene nucleus, in order to increase the out-of-plane twist of the appended rings. The analogues were prepared by the benzylation of appropriate deoxybenzoins, followed by Friedel-Crafts cyclic alkylation-dehydration. Comparison of the X-ray crystal structure of one analogue with unsubstituted analogues confirms the torsional perturbation effected by the ortho substituent. The torsional disposition of the C-2 aryl group in the substituted diphenylindenes is further investigated by UV (absorbance maxima and molar absorptivities), fluorescence (Stokes' shift), and NMR (chemical shifts). These spectroscopic measurements indicate increasing twisting between the C-2 aryl substituent and the indene system according to the following order: 3-ring o-Me indene 9f less than diphenylindene 15 = 20 degrees less than 3-ring o-F-indene 9c less than 1-Me-indene 16 less than 2-ring o-F-indene 9b less than 2-ring o-Me indene 9e = 63 degrees. The binding affinity of these analogues to the estrogen receptor was evaluated by a competitive radiometric receptor binding assay. While o-fluoro or o-methyl substitution on the 3-ring increases binding only slightly, binding of the o-fluoro 2-ring analogue is increased ca. 6-fold and the o-methyl analogue 11-fold, giving, in the latter case, a compound with an affinity equivalent to that of estradiol. The increase in binding affinity afforded by ortho substitution correlates with the increase in the torsion angle of the C-2 aryl ring. A thermodynamic evaluation of the receptor fit (Andrews, P. R.; Craik, D. J.; Martin, J. L. J. Med. Chem. 1984, 27, 1648) indicates that, for the o methyl 2-ring analogue, the effect of the ortho substitution on increasing receptor binding appears to be a combination of increased surface area due to the substituent itself, together with a change in surface area of the ligand that results from the increased torsion of the two aryl rings. An o-fluoro substituent on the 2-ring provides a compromise between the relative planarity required for high fluorescence intensity and the molecular shape needed for increased estrogen receptor binding affinity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213826 TI - Synthesis of acyclic and dehydroaspartic acid analogues of Ac-Asp-Glu-OH and their inhibition of rat brain N-acetylated alpha-linked acidic dipeptidase (NAALA dipeptidase). AB - The following structural and conformationally constrained analogues of Ac-Asp-Glu OH (1) were synthesized: Ac-Glu-Glu-OH (2), Ac-D-Asp-Glu-OH (3), Ac-Glu-Asp-OH (4), Ac-Asp-Asp-OH (5), Ac-Asp-3-aminohexanedioic acid (6), Ac-3-amino-3 (carboxymethyl)propanoyl-Glu-OH (7), N-succinyl-Glu-OH (8), N-maleyl-Glu-OH (9), N-fumaryl-Glu-OH (10), and Ac-delta ZAsp-Glu-OH (11). These analogues were evaluated for their ability to inhibit the hydrolysis of Ac-Asp-[3,4-3H]-Glu-OH by N-acetylated alpha-linked acidic dipeptidase (NAALA dipeptidase) in order to gain some insight into the structural requirements for the inhibition of this enzyme. Analogues 4-6 and 9 were very weak inhibitors of NAALA dipeptidase (Ki greater than 40 microM), while 2, 3, and 7 with Ki values ranging from 3.2-8.5 microM showed intermediate inhibitory activity. The most active inhibitors of NAALA dipeptidase were compounds 8, 10, and 11 with Ki values of 0.9, 0.4, and 1.4 microM, respectively. These results suggest that the relative spacing between the side chain carboxyl and the alpha-carboxyl group of the C-terminal residue may be important for binding to the active site of the enzyme. They also indicate that the chi 1 torsional angle for the aspartyl residue is in the vicinity of 0 degrees. PMID- 2213827 TI - Penta- and hexadienoic acid derivatives: a novel series of 5-lipoxygenase inhibitors. AB - The synthesis of a series of pentadienoic and hexadienoic acid derivatives is reported. These compounds were tested as inhibitors of 5-lipoxygenase (5 LO) and cyclooxygenase (CO) in vitro and as inhibitors of arachidonic acid (AA) induced ear edema in mice in vivo. Their potency is compared with that of the standard inhibitors nafazatrom, BW 755C, NDGA, KME4, quercetine, and L 652,243. The most potent compound in vivo, diethyl 2-hydroxy-5-(ethylthio)-2(Z),4(Z) hexadienedioate (20) inhibited AA-induced ear edema when administered topically or orally, with an ED50 value of 0.01 mg/ear and 20 mg/kg, respectively. Among the standard compounds tested, L 652,243 was the most active compound in this test with an ED50 value of 0.01 mg/ear and 1 mg/kg po, but unlike this compound, 20 is a selective inhibitor of 5-LO (IC50 = 2 microM) without any significant activity against CO (IC50 greater than 50 microM). Most of the other compounds in this series are also selective 5-LO inhibitors. PMID- 2213828 TI - 4-Heterocyclyloxy-2H-1-benzopyran potassium channel activators. AB - The reaction of 2,4-dihydroxypyridine (2) with 3,4-epoxy-3,4-dihydro-2,2-dimethyl 2H-1-benzopyran-6-carbonitrile (1) yielded the 4-[(1,2-dihydro-2-oxo-4 pyridyl)oxy] compound 3a, accompanied by small amounts of the isomeric 4-(1,2 dihydro-4-hydroxy-2-oxo-1-pyridyl) compound 4. This could also be prepared by hydrogenation of the benzyloxy derivative 5. Reaction of 3,6-pyridazinediol (10) with 1 (R = CN) gave the 4-[(1,6-dihydro-6-oxo-3-pyridazinyl)oxy] compound 11a, which in turn rearranged on heating with NaH in DMSO into the 4-(1,6-dihydro-3 hydroxy-6-oxo-1-pyridazinyl) compound 12. A series of 6-substituted analogues (R = CO2Me, CSNH2, NO2, Br) of 3a and 11a were synthesized. N-Alkylation led to compounds 14a-c (R = Me, Et, CHMe2). The 4-heterocyclyloxychromenes 9 and 16a were obtained by alkaline hydrolysis of their 3-camphorsulfonates. The racemic pyridazinyloxy compounds 11a and 14a could be resolved via their diastereomeric camphorsulfonates or camphanates. The differences between the 4 heterocyclyloxychromanols and the isomeric N-substituted compounds 4 and 12 were elucidated in the course of extensive NMR investigations. While in DMSO the former appeared to be conformationally flexible molecules the latter were rigid. All compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats, using doses of 1 mg/kg. High and long lasting activities were found for the pyridyloxy compounds 3a and 3d, the pyridazinyloxy compound 11a, and its N-alkylation products, as well as for the 3S,4R-enantiomers 20a and 22a. (-)-(3S,4R)-3,4-Dihydro-4-[(1,6-dihydro-1-methyl-6-oxo-3- pyridazinyl)oxy]-3 hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (22a) was selected for further development. PMID- 2213829 TI - Anti-HIV-1 activity, toxicity, and stability studies of representative structural families of polyoxometalates. AB - The anti-HIV-1 activity and toxicity of representative structural families of polyoxotungstates in human lymphocytes was determined. The 21 compounds examined include those derived from the following structural families: [NaSb9W21O86]18- (HPA-23), Xn+W12O40(8-n)- (Keggin), P2W18O62(6-) (Wells-Dawson), W6O19(2-) (Lindqvist), [NaP5W30O110]14- (Preyssler), and W10O32(4-) (decatungstate). The molecular architecture of each of these structural families is constituted principally by a network of bonds between d0 WVI and oxide ions. Of these, 10 show median effective concentration (EC50) values of approximately 1 microM and six have marked toxicity with a median inhibitory concentration (IC50) of less than 50 microM. Only compounds containing more than six metal atoms showed appreciable antiviral activity. Beyond this, however, no marked correlation existed between the molecular size, charge, or charge density of the polyoxometalates and their anti-HIV-1 activity. Examination of an exemplary class of polyoxotungstates, the phosphotungstates of formula A- and B-PW9O34(9-) under physiological conditions (buffered neutral aqueous media), illustrates that both isomers equilibrate rapidly to generate the same distribution of products and that this distribution depends principally on the buffer. These heretofore unappreciated complexities in the chemistry of these compounds under neutral aqueous conditions indicates interpretation or evaluation of these compounds in cell culture and other biological screens must be done with care. PMID- 2213830 TI - Binding of indolylalkylamines at 5-HT2 serotonin receptors: examination of a hydrophobic binding region. AB - Taking advantage of a proposed hydrophobic region on 5-HT2 receptors previously identified by radioligand-binding studies utilizing various phenylisopropylamine derivatives, we prepared and evaluated several N1 - and/or C7-alkyl-substituted derivatives of alpha-methyltryptamine in order to improve its affinity and selectivity. It was determined that substitution of an n-propyl or amyl group has similar effect on affinity regardless of location (i.e., N1 or C7). The low affinity of several N1-alkylpyrroleethylamines suggests that the benzene portion of the alpha-methyltryptamines is necessary for significant affinity. Whereas tryptamine derivatives generally display little selectivity for the various populations of 5-HT receptors, N1-n-propyl-5-methoxy-alpha-methyltryptamine (3h) binds with significant affinity (Ki = 12 nM) and selectivity at 5-HT2 receptors relative to 5-HT1A (Ki = 7100 nM), 5-HT1B (Ki = 5000 nM), 5-HT1C (Ki = 120 nM), and 5-HT1D (Ki greater than 10,000 nM) receptors. As a consequence, this is the most 5-HT2-selective indolylalkylamine derivative reported to date. PMID- 2213831 TI - Chemistry and structure-activity relationships of C-17 unsaturated 18-cycloalkyl and cycloalkenyl analogues of enisoprost. Identification of a promising new antiulcer prostaglandin. AB - A series of delta 17 unsaturated cycloalkyl and cycloalkenyl analogues of enisoprost was synthesized to investigate the effects of omega chain unsaturation on gastric antisecretory activity and diarrheogenic side effects. Of these, the 17E, 18-cyclopentenyl analogue 5d displayed potent gastric antisecretory activity in dogs but very weak diarrheogenic properties in rats and is the most selective prostaglandin compound discovered in these laboratories. Structurally, 5d contains both a conjugated diene and tertiary allylic alcohol in the omega chain, and these chemical features impart some interesting oxidative and acid-catalyzed epimerization and allylic rearrangement reactivities, respectively. PMID- 2213832 TI - Pyrroloisoquinoline antidepressants. 3. A focus on serotonin. AB - A collection of hexahydropyrroloisoquinoline derivatives (1-22), which represent a class of compounds that inhibit the neuronal uptake of dopamine (DA), norepinephrine (NE), and serotonin (5-HT), was investigated in vivo for serotonin potentiating properties in the mouse head-twitch and rat serotonin syndrome assays. The p-methylthio compound 3b (McN-5652-Z) was found to possess exceptional activity in these assays, and the activity was attributable almost exclusively to the (+)-6S,10bR enantiomer. Ten closely related analogues were synthesized, tested, and compared among themselves and with some previously prepared compounds, both in vivo and in vitro. Several trans diastereomers exhibited strong inhibition of 5-HT uptake and substantial potentiation of 5-HT, while the cis diastereomers (3a, 4a, and 10a) tested were virtually devoid of such activity. Although 3b was only moderately selective in inhibiting the uptake of 5-HT vs NE, its 10-substituted analogues 4b, 7b-9b had improved 5-HT selectivity relative to NE, to the extent of 20-25 times (150-200 times relative to DA). Of these more selective compounds (in vitro), only 4b and 7b had substantial activity in vivo. Sulfoxide 11b appeared to function as a prodrug of 3b in vivo. PMID- 2213833 TI - A Free-Wilson/Fujita-Ban analysis and prediction of the analgesic potency of some 3-hydroxy- and 3-methoxy-N-alkylmorphinan-6-one opioids. AB - Herein we describe a Free-Wilson/Fujita-Ban QSAR (quantitative structure-activity relationship) analysis of the analgesic potency of over 50 semisynthetic opioid narcotics. The 3-hydroxy- and 3-methoxy-N-alkylmorphinan-6-ones of B/C-cis and trans stereochemistry include compounds exhibiting structural variation at five positions [N-methyl (C17), oxygen at C3, C4-C5 oxygen bridge, alkyl substituents at C7 and C8]. The pharmacological parameter correlated was the analgesic potency (-log ED50) exhibited on abdominal contractions produced by acetylcholine injection in mice. A satisfactory correlation was obtained only by assuming interdependent contributions of the substituents on C17 and O(C3), with which it was possible to explain 75% of the variance. Phenolic compounds (3-OH) behave somewhat differently from the methyl ethers (3-OCH3), and in both series the substituents on C8 have a size-dependent negative contribution, implying steric hindrance at their contact point on the receptor. With use of this correlation the potency of five further members of the series was predicted. Subsequent testing fully confirmed the validity of the correlation since the measured potencies were, within experimental error, equal to those calculated. In a further refinement, phenolic compounds were considered separately from the ethers, and it was found that the contribution of the substituents on C17, C7, and C8 remained similar in sign and magnitude but not that of the furan oxygen. This analysis allows us to conclude that if both phenolic and nonphenolic members of this series act on the same receptor they must bind at different subsites or in alternate modes, supporting an earlier proposal in the literature. PMID- 2213834 TI - Imidazodiazepinediones: a new class of adenosine receptor antagonists. AB - A series of imidazo[4,5-e][1-4]diazepine-5,8-diones were synthesized from hypoxanthines. Certain of these cyclic homologues of caffeine, theophylline, theobromine, 3-isobutyl-1-methylxanthine, and enprofylline were inhibitors of binding of adenosine analogues to rat brain A1 and A2 adenosine receptors and were antagonists of A2 adenosine receptors stimulatory to adenylate cyclase in rat PC12 cell membranes. Activity at adenosine receptors was lower than the corresponding xanthines, perhaps because imidazodiazepinediones contain a boat shaped seven-membered ring rather than the planar heteroaryl ring system of the xanthines. The imidazodiazepinediones had low affinity for brain benzodiazepine sites. PMID- 2213835 TI - 7-Deaza-2-phenyladenines: structure-activity relationships of potent A1 selective adenosine receptor antagonists. AB - A series of derivatives of 7-deazapurines with varying substituents in the 2-, 6 , and 9-position was synthesized in an attempt to improve the adenosine receptor affinity and A1 or A2 selectivity. The adenosine receptor affinities were assessed by measuring the inhibition of [3H]-(R)-N6-(phenylisopropyl) adenosine (R-PIA) binding to rat brain A1 and inhibition of [3H]-5'-(N ethylcarboxamido)adenosine (NECA) binding to rat striatum A2 adenosine receptors. A selected set of compounds representing the main structural variations was further examined in adenosine receptor coupled adenylate cyclase assays. All tested compounds antagonized the inhibition of adenylate cyclase elicited by interaction of R-PIA with A1 receptors in rat fat cell membranes and the activation of adenylate cyclase elicited by interaction of NECA with A2 receptors of pheochromocytoma PC12 cell membranes. The results indicate that 7 deazahypoxanthines have a potential for A2 selectivity, while all 7-deazaadenines are A1 selective. Introduction of a phenyl residue in the 2-position of 7 deazaadenines increases A1 activity tremendously. 2-(p-Chlorophenyl)-7,8-dimethyl 9-phenyl-7-deazaadenine (29) is potent and specific for the A1 receptors of rat brain (Ki = 122 nM), having no affinity for the A2 receptors of rat striatum. The compound has low activity at the A2 receptors of rat PC12 cell membranes where it appears to act as a noncompetitive inhibitor. A 1-phenylethyl substituent at the 9-position was found to be superior to a phenyl residue in terms of A1 affinity. The most potent A1 antagonist in the present series is the highly A1 selective (790-fold) (R)-7,8-dimethyl-2-phenyl-9-(1-phenylethyl)-7-deazaadenine (31, Ki = 4.7 nM), which is 30-35 times more potent at A1 receptors than its S enantiomer. The solubility of six of the potent 7-deaza-2-phenyladenines was determined by means of an A1 binding assay. Chloro substitution of the 2-phenyl ring appeared to improve the solubility as well as the solubility over A1 affinity ratio of 9 phenyl- and 9-(1-phenylethyl)-substituted 7-deazadenines. PMID- 2213836 TI - Synthesis and antimicrobial and cytotoxic activities of pyrrole-containing analogues of trichostatin A. AB - A number of aroylpyrroleacrylic acid derivatives were synthesized by standard procedures and evaluated for cytotoxicity in Vero cells and for capacity to inhibit the multiplication of viruses, bacteria, and fungi. While none of the test compounds showed any activity against bacteria and fungi, most of them inhibited the replication of some DNA viruses at concentrations allowing the exponential growth of uninfected cells. In particular three compounds (8, 9c, and 10h) showed an antiviral activity at doses that were from 4- to greater than 8 fold lower than the maximum nontoxic doses. PMID- 2213837 TI - 8-Substituted 5-[(aminoalkyl)amino]-6H-v-triazolo[4,5,1-de]acridin-6-ones as potential antineoplastic agents. Synthesis and biological activity. AB - A series of 8-substituted 5-[(aminoalkyl)amino]-6H-v-triazolo[4,5,1-de]acridin-6 ones (2), structurally related to the imidazoacridinones (1), was synthesized and tested for cytotoxic and antineoplastic activity. Preliminary biological results indicated that the 8-OH derivatives possess the highest antitumor activity. No relationship has been found between the nature of the C-8 substituent and antitumor activity. PMID- 2213838 TI - Synthesis and anticonvulsant and sedative-hypnotic activity of 4-(alkylimino)-2,3 dihydro-4H-1-benzopyrans and -benzothiopyrans. AB - A series of 4-(alkylimino)-5-hydroxy-7-alkyl-2,3-dihydro-4H-1-benzopyrans and thiopyrans were synthesized and evaluated for anticonvulsant activity. Preliminary screening of these compounds revealed that 2,2-dimethyl-4-[(2 hydroxyalkyl)imino]-5-hydroxy-7-pentyl-2,3- dihydro-4H-1-benzopyrans 19 and 29, the 7-butyl analogue 34, and the corresponding 7-pentyl-4H-1-benzothiopyrans 38 and 39 had the most promising anticonvulsant activity. Synthesis of both enantiomers of 29 and 39 indicated that the R isomers 30 and 40 were the most active and showed very good protection against MES, pentylenetetrazole, and mercaptopropionic acid induced seizures after oral administration in mice. In the Irwin test these compounds showed a generalized depressant activity but at dosages higher than those showing anticonvulsant activity, whereas acute toxicity after oral administration was low (LD50 higher than 400 mg/kg). PMID- 2213839 TI - Nonsteroidal cardiotonics. 3. New 4,5-dihydro-6-(1H-indol-5-yl)pyridazin-3(2H) ones and related compounds with positive inotropic activities. AB - A series of substituted indolyldihydropyridazinones and related compounds 1-18 were synthesized and evaluated for positive inotropic activity. In rats, most of these indole derivatives produced a dose-related increase in myocardial contractility with little effect on heart rate and blood pressure. Compound 13, 4,5-dihydro-5-methyl-6-(2-pyridin-4-yl-1H-indol-5-yl)pyrazin-3(2H) -one (BM 50.0430), was further investigated in cats. The increase in contractility in this animal model was not mediated via stimulation of beta-adrenergic receptors. After oral administration of 1 mg/kg to conscious dogs, compound 13 and pimobendan were still active after 6.5 h. However, the cardiotonic effect of 13 was at least 2 fold that of pimobendan after this period of time. The structural requirements necessary for optimal cardiotonic activity within this novel class of indole derivatives are a heterocyclic aromatic ring in position 2, a hydrogen or a methyl group in position 3, and a dihydropyridazinone ring system in position 5 of the indole. PMID- 2213840 TI - Genetics services in the community. PMID- 2213841 TI - Cystic fibrosis screening and community genetics. PMID- 2213843 TI - On the variable effect of mosaic normal/balanced chromosomal rearrangements in man. PMID- 2213842 TI - Genetics of congenital nemaline myopathy: a study of 10 families. AB - In order to investigate the inheritance in congenital nemaline myopathy (CNM), we studied the family histories and pedigrees of 13 patients with CNM from 10 families, and the 20 patients, by physical examination, single fibre electromyography, ultrasonography of muscles, measurement of serum creatine kinase, muscle biopsy, and electrophoresis of muscle proteins. None of the parents was affected. In three families there were two affected children. Of the parents, 15 showed deficiency of type 2B muscle fibres, and all except one father showed some other minor neuromuscular abnormality. These may represent heterozygous manifestations of recessive gene. Most of the ancestors came from sparsely populated rural communities in the west of Finland. We conclude that in the Finnish CNM patients, the mode of inheritance appears to be recessive. Apart from a few instances of dominant inheritance, most cases published also seem compatible with recessive inheritance. PMID- 2213844 TI - Health visitors' awareness and perception of clinical genetic services. AB - A questionnaire was sent to 84 health visitors to assess their awareness and perception of genetic services and how they perceived their role in the referral of patients. The study showed that while health visitors had a reasonable knowledge of the more obvious aspects of genetic services, there were a number of areas in which they were unsure. The respondents did not identify themselves as prime initiators in the process of referring patients to a genetic service, although they appeared able to identify families on their caseloads for whom this service may be relevant. Health visitors viewed their own knowledge of genetics as poor, a factor which may account for the low referral rate initiated by this group of professionals. The respondents attached importance to genetic issues and 76 (95%) wished to be better informed about the subject. It is suggested that the inclusion of genetics as part of an in-service training programme might fulfil this need and lead to greater advocacy of genetic services among the families in their care. These findings are of interest in view of the proposals within the recent Royal College of Physicians report (Prenatal screening and genetic counselling) suggesting that community genetic services should make use of primary health care workers such as health visitors. PMID- 2213845 TI - Dyggve-Melchior-Clausen syndrome. PMID- 2213846 TI - Partial duplication of the long arm of chromosome 6: a clinically recognisable syndrome. AB - Reciprocal translocations involving the short arm of acrocentric chromosomes can segregate to produce partial duplications without associated deletions. We present a case of an infant with a 46,XY,-15,+der(15),T(6;15)(q23;p12)pat chromosome complement. The infant had multiple congenital abnormalities including cranial anomalies, facial dysmorphism, anterior webbing of the neck, cardiac anomalies, and joint contractures. From a comparison of the infant's phenotype with 20 other patients with a similar duplication, it is evident that partial duplication of the long arm of chromosome 6 is a clinically diagnosable syndrome. PMID- 2213848 TI - Conference on gene therapy, Royal College of Physicians, London, 1 March 1990. PMID- 2213847 TI - A new apparently folate sensitive fragile site, 5q35. PMID- 2213849 TI - Pachygyria, joint contractures, and facial abnormalities: a new lethal syndrome. PMID- 2213850 TI - The CHARGE association. PMID- 2213851 TI - The Moebius syndrome: aetiology, incidence of mental retardation, and genetics. PMID- 2213852 TI - Relationship of serum total calcium and albumin and total protein in owl monkeys (Aotus nancymai). AB - A positive linear relationship was found between total calcium and albumin and between total calcium and total protein in the serum of 205 owl monkeys. Adjustment formulas for calcium were derived: adjusted calcium (mg/dl) = measured calcium (mg/dl) - 0.84 [albumin (g/dl)] + 3.8 and adjusted calcium (mg/dl) = measured calcium (mg/dl) - 0.82 [total protein (g/dl)] + 6.5. Adjusted calcium calculations for monkeys based on albumin concentration were similar to those for man and dogs, but different from those based on total protein. PMID- 2213853 TI - Intrauterine insemination with ultrasound guidance in the long-tailed macaque (Macaca fascicularis). AB - Techniques used for the artificial insemination of macaques have primarily involved instillation of the ejaculate into the vagina or cervical canal. Intrauterine insemination has been performed previously but only as a surgical procedure. The application of ultrasound-guided techniques for this purpose provides a method for efficiently inseminating macaques in a relatively noninvasive fashion. This report describes the successful transabdominal ultrasound-guided insemination of the long-tailed macaque and the potential application of this procedure to a variety of nonhuman primate species. PMID- 2213854 TI - New methodology for measuring blood pressure in awake baboons with use of behavioral training techniques. AB - Adult male baboons were behaviorally conditioned to extend an arm outside of the living cage and to accept repeated cuff inflations for manual auscultatory blood pressure measurements. Frequency distributions of systolic and diastolic blood pressure for both normotensive and renovascular hypertensive baboons generally were normally distributed. The procedure accurately tracked rapid changes in blood pressure after oral administration of antihypertensive drugs. Advantages over direct arterial cannulation for blood pressure measurement during extended, chronic experiments are discussed. PMID- 2213855 TI - Familial incidence of multiple births in a colony of chimpanzees (Pan troglodytes). AB - This paper describes the incidence of multiple births in the Yerkes Chimpanzee colony for a period of about 63 years. Pedigrees are presented for all multiple births. They demonstrate the recurrence of twins in relatively few family lines which can be traced back to a small number of ancestors. The findings suggest that twinning is a family trait in chimpanzees and they support the hypothesis that the incidence of multiple births is genetically influenced in this colony. In addition, a relatively high level of inbreeding may have enhanced the incidence of multiple births in these family lines. Similar findings are known from human populations. PMID- 2213856 TI - Control data on pre- and neonatal survival of captive chimpanzees. AB - Colony breeding records were analyzed in order to obtain information on pre- and neonatal survival in chimpanzees. Biweekly urinary chorionic gonadotrophin testing appeared suitable for determining pregnancy age. The probability of pregnancy termination was low (0.008 per 10 days) to a pregnancy age of 180 days. Between the ages of 180-210 days it was 0.080 per 10 days, and it steadily increased to one per 10 days after 240 days of age. There were no livebirths before 190 days of pregnancy age. Thereafter, the probability of a delivery to be a livebirth rapidly increased to about 0.90 after 210 days of pregnancy age. Infant mortality was less than 0.026 during the first two years of life. PMID- 2213857 TI - Increased carbon monoxide excretion in Bolivian squirrel monkeys with fasting hyperbilirubinemia. AB - Pulmonary carbon monoxide (CO) excretion rates (VeCO) were 50% greater, on average, in Bolivian squirrel monkeys (BoSMs) which exhibit a unique fasting hyperbilirubinemia (FH), than in fasted control Brazilian squirrel monkeys (BrSMs). Since the catabolism of heme produces equimolar amounts of CO and bilirubin, the increased VeCOs are consistent with concurrent increases in endogenous bilirubin production rates. Tin-protoporphyrin, a competitive inhibitor of heme oxygenase, significantly decreased both the VeCO and serum bilirubin level in fasted BoSMs. Overproduction of bilirubin may be responsible in part for the marked FH in BoSMs. PMID- 2213858 TI - The refractometer index as a correction factor for urinary estradiol in rhesus females. AB - Refractometer indexes were standardized and found to be highly correlated (r = 0.831) to actual creatinine levels. Urinary estradiol corrected by creatinine levels and refractometer indexes were found to be highly correlated (r = 0.857). Predicted ovulation was the same day in 86% of the ovulatory cycles predicted by creatinine and refractometer corrected estradiol levels. Refractometer indexes may be used in place of creatinine levels to correct for urine concentration fluctuations when predicting ovulation in the rhesus female. PMID- 2213859 TI - Spontaneously occurring congenital polycystic kidney in a cynomolgus monkey (Macaca fascicularis). AB - Congenital polycystic kidney disease was diagnosed at necropsy in a stillborn male cynomolgus monkey (Macaca fascicularis). This case was very similar to infantile polycystic kidney disease in man and the rhesus monkey, except that no increase in number of intrahepatic bile ducts was observed. PMID- 2213860 TI - Extraosseous osteosarcoma in a nonhuman primate (Macaca mulatta). AB - A case of a very rare malignant bone-forming sarcoma, which was located in the soft tissue but had no anatomic attachment to bone, is presented. This tumor originated in the subcuticular tissue over the right scapula and was histologically composed of sheets of anaplastic spindle cells that produced osteoid. The tumor recurred twice before the animal was killed. The recurrent masses produced less osteoid and were generally less differentiated histologically than the initial tumor. PMID- 2213862 TI - Psychological profiles help select ideal dental teams. PMID- 2213863 TI - Finding and keeping good staff. PMID- 2213861 TI - K-Cl cotransport in LK sheep erythrocytes: kinetics of stimulation by cell swelling. AB - The effects of osmotic cell swelling were studied on the kinetics of Cl-dependent K+ influx, K-Cl cotransport, in erythrocytes from sheep of the low K+ (LK) phenotype. Swelling approximately 25% stimulated transport by increasing maximum velocity (Jmax) approximately 1.5-fold and by increasing apparent affinity for external K (Ko) nearly twofold. Dithiothreitol (DTT) was shown to be a partial, reversible inhibitor of K-Cl cotransport. It inhibited in cells of normal volume by reducing Jmax more than twofold; apparent affinity for Ko was increased by DTT, suggesting that DTT stabilizes the transporter-Ko complex. Cell swelling reduced the extent of inhibition by DTT: Jmax was inhibited by only about one third in swollen cells, and apparent affinity was only slightly affected. This result suggested that DTT does not act directly on the transporter, but on a hypothetical regulator, an endogenous inhibitor. Swelling relieves inhibition by the regulator, and reduces the effect of DTT. Reducing intracellular Mg2+, Mgc, stimulated cotransport. Swelling of low-Mg2+ cells stimulated transport further, but only by raising apparent affinity for Ko nearly threefold: Jmax was unaffected. Thus effects of swelling on Jmax and apparent affinity are separable processes. The inhibitory effects of Mgc and DTT were shown to be additive, indicating separate modes of action. There appear to be two endogenous inhibitors: the hypothetical regulator, which holds affinity for Ko, low; and Mgc, which affects Jmax, perhaps by holding some transporters in an inactive form. Swelling stimulates transport by relieving both types of inhibition. PMID- 2213864 TI - Hiring, firing and drug testing: a legal guide for the dentist as employer. PMID- 2213865 TI - Employee training: complying with occupational safety and health standards. 1. PMID- 2213866 TI - Motivating auxiliaries. PMID- 2213867 TI - Work stress, nonwork stress, and health. AB - This paper examines the interface between work stress and nonwork stress and how it relates to health. Results indicate that the way people feel at work is largely a function of conditions at work. Similarly, the way people feel outside of work is largely a function of things that occur outside the job. Both work and nonwork stress are independently associated with physical and mental health, although the relationship between nonwork stress and health is slightly stronger. Excessive demands or stresses in one domain can interfere with life in the other. Such conflict operates equally in both directions. When present it can be an added source of stress and adversely affect health. Taken together these findings suggest that the stress people experience at work is not simply a reflection of their "personal problems." This has implications for the design of health promotion and stress prevention programs in the workplace. PMID- 2213868 TI - Social and behavioral factors associated with high-risk sexual behavior among adolescents. AB - Relationships among risky sexual behaviors, other problem behaviors, and the family and peer context were examined for two samples of adolescents. Many adolescents reported behaviors (e.g., promiscuity or nonuse of condoms) which risked HIV or other sexually transmitted disease infection. Such risky behaviors were significantly intercorrelated. Consistent condom use was rare among those whose behavior otherwise entailed the greatest risk of infection. In both samples, an index of high-risk sexual behavior was significantly related to antisocial behavior, cigarette smoking, and illicit drug or alcohol use. Social context variables, including family structure, parenting practices, and friends' engagement in problem behaviors, were associated with high-risk sexual behavior. Finally, for sexually active adolescents, problem behaviors and social context variables were predictive of nonuse of condoms. Results were consistent across the two studies and regression weights held up well under cross-validation. PMID- 2213869 TI - Stressful life events, Type A behavior, and the prediction of cardiovascular and total mortality over six years. MRFIT Group. AB - The relationship between stressful life events and subsequent mortality and morbidity were determined prospectively over 6 years for 12,866 men participating in the Multiple Risk Factor Intervention Trial (MRFIT). Aslo evaluated was the impact of life events on cardiovascular outcomes for persons exhibiting and not exhibiting coronary prone (Type A) behavior. Subjects completed life events checklists at baseline and each of five annual visits. Participants were also administered the Jenkins Activity Survey measure of Type A behavior at baseline and a subsample of 3110 participants was categorized as to behavior type based on the structured interview assessment method. Cox proportional hazard analyses indicated that number of life events experienced during each of 6 years of follow up was unrelated to risk in the subsequent year of CHD death or fatal plus nonfatal MI and was inversely related to total mortality. The impact of life events on cardiovascular risk did not differ by behavior type category. PMID- 2213870 TI - The efficacy of social-influence prevention programs versus "standard care": are new initiatives needed? AB - This study evaluates the effects of a school-based smoking prevention program after 1 year, using school (22 middle/elementary schools, 15 high schools) as both the unit of randomization and the unit of analysis. The multigrade level (grades 6 through 9) intervention was designed to address comprehensively the social influence factors that encourage smoking. Teacher survey data indicated that treatment schools had a median of 10 classroom sessions devoted to tobacco/drug use education, 5 of which were the sessions designed for this evaluation, and control schools had also dedicated a median of 10 classroom sessions to tobacco/drug education. Thus, the study evaluated the incremental effects of the social influence intervention compared to "standard-care" curricula. Among those who reported smoking one or more cigarettes in the month prior to the intervention, there was a significant treatment effect on rate of smoking at one year, but no grade level, gender, or interaction effects. The 1 year covariate-adjusted smoking rate among pretest smokers in the treatment schools was 76.6 cigarettes per month, compared to 111.6 cigarettes per month in control schools, a 31.4% difference. These effects were not accounted for by differential subject attrition. The analyses for nonsmokers, however, showed no significant effects, and the program did not affect self-reported alcohol or marijuana use. Taken together with the results of other prevention studies, these results point to the need for the development and evaluation of new initiatives to prevent substance use. PMID- 2213871 TI - Disease and symptom severity, functional status, and quality of life in chronic bronchitis and emphysema (CBE). AB - A path analysis model examined interrelationships among variables significantly associated with chronic dyspnea in chronic bronchitis and emphysema (CBE) and the relative influence of these variables on each other and on functional status and quality of life. Results from the 45 adults (mean age, 61) with moderate CBE disease severity showed that dyspnea severity has a sizable effect on functional status and quality of life. Disease severity was more strongly related to functional status than to quality of life. Depression and mastery had the strongest total effects on quality of life. Dyspnea severity had strong but separate effects on functional status and quality of life. From these preliminary results, it is suggested that a direct focus on psychologic interventions to ameliorate depression and improve mastery is likely to improve quality of life with some resultant positive effect on functional status. PMID- 2213872 TI - Dentists' technical competence, communication, and personality as predictors of dental patient anxiety. AB - Previous research has found that many factors influence patients' dental anxiety, many of which are related to the practitioner's technical and interpersonal skill. Unfortunately, a confirmatory factor analysis of scales used in dental anxiety research revealed numerous problems with the measurement devices. The Spielberger State-Trait Anxiety Inventory (STAI) split into two subscales: calmness and anxiety. The Corah Dental Anxiety Scale (CDAS) was unidimensional but was unable to detect relationships between anxiety and interpersonal or communication factors. Interestingly, patient satisfaction, dentist behavior, and empathy items did not load on independent scales, as previously reported in the literature. Instead, five clusters were detected: positive and negative communication, positive and negative interpersonalness, and perceived technical competence. PMID- 2213873 TI - Nicotine effects on biofeedback training. AB - Biofeedback involving hand warming has become a frequently used procedure in health and stress management programs. The present research examined the effects of smoking on the ability to learn temperature control during biofeedback training. Three groups of female college students were compared: groups of smokers who smoked prior to the biofeedback session were compared to smokers who did not smoke and to nonsmokers. The results showed that the greatest increase in skin temperature was for nonsmokers, followed by smokers who did not smoke for at least 1 hr before the biofeedback session. The group of smokers who smoked just prior to the biofeedback were not able to increase their skin temperature. The basal skin temperature measured before treatment was higher for smokers than nonsmokers. The results are discussed in terms of the paradoxical physiological arousing effects and the self-reported tranquilizing effects of smoking. PMID- 2213874 TI - Electrophysiologic monitoring of the facial nerve during basal cranial and posterior fossa surgeries. PMID- 2213875 TI - Oral contraceptive pills. Part I: Formulations, selection and common side effects. AB - Development of hormonal contraception as a safe and effective means of birth control has evolved during the past 50 years. The first effective oral contraceptive pill was Enovid which was introduced by Searle in 1960. Now, low dose OCP are the most popular reversible method of contraception. Some 50 million women worldwide and 10 million in the United States utilize them. Understanding effectiveness, side effects, complications, and benefits has led to substantial changes in these preparations. Part II of this article will be printed in the future. It will address serious complications and health benefits. PMID- 2213876 TI - What is a doctor's relative worth? PMID- 2213877 TI - Cocaine: a primer for providers of perinatal care. PMID- 2213878 TI - Government limits access to care. PMID- 2213879 TI - Crystallographic studies of 3-ketoacylCoA thiolase from yeast Saccharomyces cerevisiae. AB - Good diffracting crystals of 3-ketoacylCoA thiolase (EC 2.3.1.16) from yeast Saccharomyces cerevisiae have been obtained. The crystals diffract to at least 2.4 A. The space group of these crystals is P2(1)2(1)2(1), with cell dimensions a = 71.8 A, b = 93.8 A and c = 119.9 A. There is one dimer per asymmetric unit. PMID- 2213880 TI - Crystallization and preliminary X-ray study of a recombinant cutinase from Fusarium solani pisi. AB - Recombinant cutinase from Fusarium solani pisi is expressed and excreted with very high yields in Escherichia coli cultures. Cutinase was crystallized at 20 degrees C using the vapour diffusion technique, with polyethylene glycol 6000 as precipitant. Best crystals were obtained at pH 7.0 with polyethylene glycol 6000 as precipitant. Best crystals were obtained at pH 7.0 with polyethylene glycol at 15 to 20%. They are monoclinic, with space group P2(1) and cell dimensions a = 35.1 A, b = 67.4 A, c = 37.05 A and beta = 94.0 degrees; they diffract beyond 1.5 A resolution. The asymmetric unit contains one molecule of 22,000 Da (Vm = 1.98 A3/Da; 38% water). PMID- 2213881 TI - Evolution of the autosomal chorion cluster in Drosophila. III. Comparison of the s18 gene in evolutionarily distant species and heterospecific control of chorion gene amplification. AB - We present a total of 6.1 x 10(3) base-pairs of DNA sequences, encompassing the s18 gene and flanking regions within the autosomal chorion cluster of three Drosophila species. Against a background of extensive divergence in the intron and even in parts of the coding region, islands of strong sequence conservation are evident. These are particularly notable in the 5' flanking DNA where they extend to approximately -600 base-pairs from the transcription start site. The most conserved segment of the entire chorion cluster is 71 base-pairs in the s18 5' flanking DNA, which in D. melanogaster is part of a region defined functionally as containing amplification control elements (ACE3 region). Transformation analysis, using chimeric transposons of D. melanogaster and D. grimshawi DNA, revealed that amplification control elements of D. grimshawi can support amplification in D. melanogaster. The functionally defined ACE3 region of D. grimshawi includes the conserved 71 base-pair segment, but also non-conserved sequences further upstream, which apparently enhance amplification. PMID- 2213882 TI - Escherichia coli minichromosomes: random segregation and absence of copy number control. AB - Minichromosomes, i.e. plasmids that can replicate from an integrated oriC, have been puzzling because of their high copy numbers compared to that of the chromosomal oriC, their lack of incompatibility with the chromosome and their high loss frequencies. Using single cell resistance to tetracycline or ampicillin as an indicator of copy number we followed the development of minichromosome distributions in Escherichia coli cells transformed with minichromosomes and then allowed to grow towards the steady state. The final copy number distribution was not reached within 15 to 20 generations. If the minichromosome carried the sop (partitioning) genes from plasmid F, the development of the copy number distribution was further drastically delayed. We conclude that E. coli cells have no function that directly controls minichromosomal copy numbers, hence the absence of incompatibility in the sense of shared copy number control. We suggest that minichromosomes are subject to the same replication control as the chromosome but segregate randomly in the absence of integrated partitioning genes. This, combined with evidence that the lowest copy number classes are normally present despite high average copy numbers, can account for the high loss frequencies. PMID- 2213883 TI - Changes in conserved region 2 of Escherichia coli sigma 70 affecting promoter recognition. AB - We describe a mutation in rpoD, the gene encoding the sigma 70 subunit of RNA polymerase, which alters the promoter specificity of the holoenzyme in vivo. The mutant sigma causes a substantial and specific increase in the activity of mutant ant and lac promoters with a T.A to C.G substitution at position -12, the first position of the -10 hexamer. The rpoD mutation is a single base-pair substitution causing a Gln----His change at position 437, which is in a domain of conserved region 2.4 that is predicted to form an alpha-helix. Gln437 would lie one turn of the alpha-helix away from Thr440, which was previously implicated in recognition of position -12. The rpoD-QH437 mutation described here lends further support to the model that region 2.4 of sigma is involved in recognition of the 5' end of the -10 hexamer. In addition, two rpoD mutations with non-specific effects on promoter recognition are described. PMID- 2213884 TI - Quantitation of photochromism of sensory rhodopsin-I by computerized tracking of Halobacterium halobium cells. AB - The swimming behavior of Halobacterium halobium is controlled by light which acts through retinal photoreceptor proteins. The sensing of near-ultraviolet (u.v.) was proposed to be mediated by the thermally metastable intermediate SR-I373 that is formed upon orange light absorption by sensory rhodopsin-I (SR-I). In order to test the validity of this proposal, we analyzed the photochromic behavior of the functional near-u.v. receptor in situ by use of an automated cell tracking system. The system was specifically designed for detection of swimming reversals in individual cells and calibrated with a straight-swimming mutant of H. halobium. Quantitative analysis of the response of the cells to near-u.v. revealed that orange background light increased the number of active near-u.v. receptor molecules. The intensity-dependence of this effect fitted into the kinetic scheme of a photochromic receptor pigment. The half-life of the functional near-u.v. receptor species was determined under continuous orange background light and found to be similar to that of the SR-I373 intermediate of sensory rhodopsin-I in intact cells. These results clearly support the assignment of the near-u.v. receptor to SR-I373. The kind of kinetic analysis described here, might be a useful tool in assigning spectroscopic data of pigments to photoreceptor function also in other organisms. PMID- 2213885 TI - Cell surface changes of in situ macrophages induced by superimposed antigen. AB - Mice received an injection of sheep erythrocytes (SRBC) into the footpad " prepared" or "not prepared" with a 7-day-prior injection of a protein-bound polysaccharide from Coriolus versicolor (PSK; Krestin), and the ultrastructure of in situ macrophages was studied at various intervals after the injection. A single SRBC injection into the footpad induced linear cell arrangements of several macrophages. The macrophages showed no prominent morphological alterations after SRBC digestion. When PSK-stimulated subcutaneous macrophages were challenged by SRBC, they rapidly sent out numerous long cytoplasmic projections which radiated in all directions. Such projections of neighboring macrophages tended to contact one another. At the following stage, a pronounced sequential alteration was noted, characterized by the interlocking of elongated projections. This provided massive aggregations of "activated" macrophages. These observations suggest the possibility that intercellular communication among "activated" macrophages was elicited, particularly in the subcutaneous region, and maintained through an intensive interaction of cytoplasmic projections. Further, the present results histologically support our previous report which shows that the "PSK-prepared" footpad site but not the "prepared" one supports development of a splenic humoral immune response following injection of superimposed SRBC. PMID- 2213886 TI - Postnatal development of the skin of the marsupial native cat Dasyurus hallucatus. AB - Skin development of the Northern native cat was examined from birth to weaning at 150 days post partum. An outer layer of cells, termed the periderm or epitrichium, is present on the epidermis of the newborn. This layer of cells is not discernible at 7 days post partum. Skin development of the native cat differs from that of the eutherian mammal. The periderm of the eutherian is no longer discernible when the developing hairs first penetrate the epidermis. In the marsupial, this loss of the periderm occurs well before the appearance of follicles. Melanocytes and Langerhans cells are seen at day 23 post partum, follicles at day 30, sebaceous glands at day 59, and sweat glands at day 67. Thus, when the mother first leaves her young in the nest at about days 60 to 70 of lactation, the skin is at a stage of development that will assist the young with thermoregulation. The skin continues to develop throughout lactation and attains an adult appearance by day 150 post partum. PMID- 2213887 TI - Morphology and morphometry of motor endings on macaque intrafusal fibers. AB - The ultrastructural studies have shown three types of motor endings in the macaque intrafusal fibers: 1) unindented axon terminals with smooth or shallowly folded postsynaptic membrane; 2) indented terminals with few postsynaptic folds; and 3) indented terminals with heavily folded postsynaptic membrane. The terminals on bag 1 and chain fibers were generally more indented than those on the bag 2 fibers. Deeply indented terminals with highly folded postsynaptic membranes were noticed on the bag 1 and chain endings in spindles from lumbrical but not the biceps muscle. In the individual intrafusal fibers from the biceps and lumbrical spindles, the degree of indentation did not correlate with the extent of postsynaptic folding (P greater than .01). Endings on bag 1 and chain fibers in the lumbrical spindles showed a positive correlation between indentation of terminals and their distance from the primary sensory endings (P less than .01), whereas the lumbrical bag 2 endings and the biceps intrafusal endings did not (P greater than .01). The shape of the intrafusal motor endings thus is independent of their location but dependent on the type of intrafusal fibers. PMID- 2213888 TI - Nursing support of Healthy People 2000. PMID- 2213889 TI - National objectives for the year 2000. PMID- 2213890 TI - ATPO's support of Healthy People 2000. Association of Technical Personnel in Ophthalmology. PMID- 2213891 TI - Health promotion and disease prevention in ophthalmology. AB - There is a new trend in the US government's perception regarding health care today. It involves an increased awareness of how disease can be prevented and health promoted. The US government is supporting this concept with its Healthy People 2000 project. Specific pediatric concerns about health promotion and disease prevention in ophthalmology include amblyopia and strabismus, ophthalmia neonatorum, ocular trauma, radiation injury, xerophthalmia, herpes simplex, herpes zoster, infections and metabolic and genetic disorders. Adult health promotion/disease prevention priorities include glaucoma; trauma; diabetic retinopathy; corneal problems; iatrogenic infections; exposure keratitis; ocular toxicity from drugs, chemicals, and the environment; visual loss from neglect; and those mentioned in the pediatric area. PMID- 2213892 TI - The importance of early detection of diabetic retinopathy. AB - Diabetic retinopathy is the leading cause of blindness among people of ages 20 to 44 and is the second leading cause of blindness between the ages of 45 to 74. Most patients are unaware of the changes within their eyes. Primary medical providers caring for diabetic patients should receive greater training in fundus examination techniques and the recognition of significant retinopathy. Primary medical providers should be encouraged to perform fundus examinations at 6-month or annual routine examinations of all diabetics, and be made aware of the value of detection and treatment of high risk eyes. PMID- 2213893 TI - Partners in prevention. AB - The National Society to Prevent Blindness, formed in 1908, is the oldest voluntary agency with the singular mission to preserve sight and prevent blindness through a broad program of public and professional education, industrial and community services, and research. The interventions used by NSPB to prevent blindness and preserve sight include awareness and advocacy efforts, education, community services, information, and referral. The process for planning and implementing blindness prevention programs parallels the nursing process and the scientific method. It begins with the identification of local needs and resources and is followed by establishing objectives and methods to achieve them. PMID- 2213894 TI - Glaucoma screening. AB - The ability to screen for any disease is based on several factors (established natural history, high prevalence rates, effective treatment, and available screening tests); however, the earliest psychosocial, clinical, or electrodiagnostic changes in glaucoma are presently unknown. Public awareness of glaucoma must be increased. Mass screenings not only aid in the detection of disease, but through their promotion by the local media, they also assist in augmenting the general public's awareness of eye health. The future of more effective screening may lie in more objective or automated testing that could be performed by lesser trained personnel. PMID- 2213895 TI - The Bright Eyes Project: a 20-year effort to prevent blindness. AB - The Bright Eyes Project is a unique collaboration between medicine, public government, and a non-profit society. The project was prompted by concern that there was a high prevalence of undetected or untreated eye problems in the elderly. The objective was to detect ocular pathology, especially in those patients not currently receiving eye care. The project succeeded in providing a mechanism for free full ophthalmic examinations to the elderly at risk. In addition, the vast numbers seen in the project provide valuable statistics on common eye pathology in the individuals over 55 years of age. PMID- 2213896 TI - Prevention of sports injuries. AB - The eye care professional has the responsibility to advise the patient of potential eye injuries in sports and the available methods of protection against injury. Polycarbonate is the lens material of choice, both plano and for prescription eye wear for athletes and other active people. Those who fabricate and dispense eye wear must be aware of the need for safety eye wear and advise patients appropriately. They should stock and distribute the material at reasonable prices. PMID- 2213898 TI - Noncontact tonometry. PMID- 2213897 TI - The nursing role in epidemiology, risk management, and patient-public education. AB - Epidemiology encompasses the identification of infectious disease, the vectors of transmission, the sources of contamination, the patient population exposed or involved, containment practices, and preventative measures to stop further transmission of the disease. Epidemic keratoconjunctivitis is a common infectious disease in ophthalmology. It can be contracted from interpersonal exposure, contact with contaminated items, or iatrogenic transmission from the health-care settings and providers. The interview process, plus patient education, is the method of epidemiologic assessment that acts as the format to dealing with the epidemic. PMID- 2213899 TI - Where have all the dropouts gone? PMID- 2213900 TI - Is the increased incidence of primary malignant brain tumors in the elderly real? PMID- 2213901 TI - Have transurethral resections contributed to the increasing incidence of prostatic cancer? PMID- 2213902 TI - Increasing annual incidence of primary malignant brain tumors in the elderly. AB - Between 1973 and 1985, total age-adjusted cancer incidence in the United States (all races, men and women) rose by 10.7%, with an average annual percentage change of +0.9%. Analysis of reported age-specific incidence of primary malignant brain tumors over the same years demonstrates that incidence rates increased dramatically between 1973/1974 and 1985. In 1985, incidence rates for persons aged 75-79, 80-84, and 85 years of age and over were 187%, 394%, and 501%, respectively, of rates in 1973/1974. Similar increases were found in both men and women, analyzed separately and combined. Average annual percentage changes in primary brain tumor incidence were +7.0%, +20.4%, and +23.4% in these age ranges, respectively. Reported incidence in younger persons varied little over the same period of time. The most common histologic type of primary brain tumor in the elderly was of glial origin, predominantly the glioblastoma multiforme and astrocytoma. These tumors are highly malignant and invariably fatal. Two possible causes may explain the increased incidence in the elderly: the introduction and extensive use of x-ray computed tomography since 1973 and/or a true increase in incidence occurring independently of diagnostic advances. PMID- 2213903 TI - Rise in prostatic cancer incidence associated with increased use of transurethral resection. AB - We examined the association between prostatic cancer incidence rates and the rates of transurethral prostatectomy to explore reasons for the nationally reported dramatic increases in incidence rates of prostatic cancer from 1973 through 1986. There was a strong correlation between both incidence of all stages of prostatic cancer combined and of localized disease and the increasing use of transurethral resection, a common surgical procedure usually performed to relieve urinary obstruction due to benign enlargement of the prostate. Our analyses suggest that increased detection of existing tumors via transurethral resection was the primary reason for the observed increase in incidence rates of prostatic cancer. However, analyses of mortality trends, particularly among nonwhites, and laboratory studies of the histologic nature of clinically asymptomatic tumors suggest that part of the increase may reflect changes in the real risk of prostatic cancer. PMID- 2213904 TI - Methionine dependency of malignant tumors: a possible approach for therapy. AB - When methionine (Met), an essential amino acid, was substituted for by its precursor homocysteine (Hcy) in the culture medium, normal cells such as fibroblasts proliferated normally. In contrast, many tumor cells failed to grow or grew at a lower rate. Met dependency is acquired simultaneously with cell transformation, as observed with HBL 100, a human mammary epithelial cell line that acquired increased malignancy as a function of in vitro passage number, and NIH/3T3 (J10), a mouse fibroblast line transformed by transfection with the human HRAS oncogene. A relationship was observed between Met dependency and metastatic potential of the RMS-21, RMS-S4T, and RMS-J1 sublines derived from RMS-0, a rat rhabdomyosarcoma cell line: the higher the metastatic potential of the cell line, the higher the concentration of Met required to maintain its proliferation. Met independent cells derived from the RMS-0 line, obtained by a progressive decrease of Met in the culture medium lost their tumorigenicity when injected into rats fed with Met-deprived diets. In addition, the in vitro motility of RMS-S4T tumor cells, a marker of metastatic capability, decreased in Met-free Hcy-complemented (Met- Hcy+) medium. Similarly, RMS-0 tumor cells, preincubated in a Met- Hcy+ culture medium for 24 hours, evidenced a decreased capacity to form lung colonies when injected into syngeneic rats: the median number of lung colonies was 27 and 3 (P less than .05) for cells cultivated in Met+ Hcy- and Met- Hcy+ media, respectively. An amino acid-defined mixture reproducing casein composition was used as a protein source in the diets fed to RMS-J1 tumor-bearing rats. Dietary substitution of Hcy for Met (i.e., met deprivation) resulted in decreased tumor growth (from 44.4 +/- 1.0 to 40.6 +/- 1.4; P less than .05) and prevention of metastatic spread (from 37 to 0; P less than .05). In conclusion, exogenous Met can be substituted for Hcy to maintain the survival of normal cells but is essential for tumor cell growth in vivo as well as in vitro. Therefore, this defect of cancerous versus normal cells could be used for a therapeutic purpose. PMID- 2213905 TI - Low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated c-erbB-2 gene. AB - We investigated the effect of an activated c-erbB-2 gene (also known as ERBB2) on metastatic potential. The c-erbB-2 gene was activated by mutation of the valine at position 659 within the transmembrane domain to glutamic acid. The activated c erbB-2 expression vector was transfected into low-metastatic-potential NL-4 cells, which were established from a metastatic variant of murine colon adenocarcinoma 26. All 10 clones produced lung metastases in BALB/c mice injected via the tail vein. Eight of the 10 clones expressed messenger RNA (mRNA) of activated c-erbB-2 and showed morphological alteration; seven of the eight produced significantly enhanced experimental metastatic activity compared with that of untransfected NL-4 or NL-4neo cells, and one had metastatic ability similar to that of NL-4 cells. Two clones did not express c-erbB-2 mRNA and did not show morphological alteration or highly metastatic phenotype. Five of the 10 clones subcutaneously implanted in the flank failed to produce metastasis in the lungs or other organs of the mice. The metastatic ability of the other five clones was not determined. These results indicate that the activated c-erbB-2 gene can enhance experimental but not spontaneous metastatic potential in NL-4 cells, suggesting participation of the gene in the metastatic process after initial arrest and lodgement in the capillary bed. PMID- 2213907 TI - Realism myth or fantasy? PMID- 2213906 TI - Unexplained excess risk of bladder cancer in men. AB - In nearly all populations studied, the risk of bladder cancer is two to four times as great in men as in women. We estimated what the gender-specific incidence rates would be in the absence of exposure to known carcinogenic factors. The data used were obtained from interviews with 2,806 white individuals with bladder cancer and 5,258 white controls in the National Bladder Cancer Study and from incidence data for 1978 from the National Cancer Institute Surveillance, Epidemiology, and End Results Program. The total age-adjusted incidence of bladder cancer was 27.5 cases per 100,000 person-years for men and 7.0 for women, yielding a ratio of 3.9. Even in the absence of exposure to cigarettes, occupational hazards, or urinary tract infection, the gender-related risk persisted; the incidence of bladder cancer was 11.0 in men and 4.1 in women, yielding a ratio of 2.7. Possible explanations for the excessive risk in men include environmental and dietary exposures not yet identified and innate sexual characteristics such as anatomic differences, urination habits, or hormonal factors. PMID- 2213908 TI - Tumor infiltrating lymphocytes. PMID- 2213909 TI - Health and smoking: a national status report. PMID- 2213910 TI - Evolving perspectives on the exposure risks from magnetic fields. AB - Based on information from suggesting effects of positive and negative polarity on cancer cells, surveys were performed on magnetic resonance imaging devices, as well as other types of equipment capable of producing appreciable magnetic fields. These surveys were performed in areas where there was a potential for both occupational and general public exposure. PMID- 2213911 TI - Survey of nonphysician tasks performed by medicine residents at a municipal hospital. AB - In June 1988, the New York State Hospital Review and Planning Council approved major revisions in the state hospital code (Part 405). Among the most controversial of these changes were the recommendations of the Bell Commission concerning limitations on resident work hours, new emergency service requirements, and enhancements in ancillary staffing. The ancillary staffing mandated by the new code regulations for teaching hospitals include the provision at all times of intravenous services, phlebotomy services, messenger services, transport services, nurses aides, housekeeping services, and other ancillary support in a manner sufficient to meet patient care needs and to prevent adverse impact on the delivery of medical and nursing care. The intent of the new health code requirements is to reduce or eliminate many of the nonphysician tasks performed by residents so as to effectively reduce their workload. We conducted a survey of Medicine residents at Queens Hospital Center to assess the amount of time they presently devote to nonphysician tasks, their perceptions of the need for ancillary staff to relieve them of the burden of these nonphysician tasks, and their evaluation of the effectiveness of a recently instituted intravenous therapy team. PMID- 2213912 TI - Burn injuries during pregnancy: an African series. AB - Seven pregnant women aged 20 to 30 years were among the burn patients treated at Ahmadu Bello University Hospital in Zaria, Nigeria. Five suffered flame burns and two were scalded. The burned surface area ranged from 4% to 80%. One patient was in the first trimester, two in the second, and four in the third. Six (86%) of the mothers and five (71%) of the fetuses survived. PMID- 2213914 TI - Patient "dumping". PMID- 2213913 TI - The significance of gallstones in children with sickle cell anemia. AB - Infection is the most common cause of high morbidity, hospitalization, and mortality in children with sickle cell anemia. In this study of pediatric sickle cell anemia patients, aged 1 to 19, we explore the hypothesis that gallstones (usually pigment stones) create a nidus of infection, predisposing the affected patients to high morbidity. Our study involved 86 children with sickle cell anemia at the Howard University Center for Sickle Cell Disease, who had been followed at the clinic for a total of 602 patient years. Review of their records revealed that patients with gallstones had a mean number of 10.24 hospitalizations and 25.35 ambulatory visits; those without gallstones had a mean number of only 4.26 hospitalizations and 13.41 ambulatory visits. In children with sickle cell anemia and gallstones, elective cholecystectomy (or, in the future, cholelithotripsy) could reduce the high morbidity caused by infection. PMID- 2213915 TI - Black Americans in crisis. PMID- 2213916 TI - Thoracolumbar compression fractures presenting with an acute ileus. AB - Corticosteroids are commonly used in the treatment of connective tissue diseases such as systemic lupus erythematosus. Although they are usually efficacious, osteoporosis leading to spine compression fractures is not uncommon. In this case report, we describe an elderly patient with systemic lupus erythematosus on long term corticosteroid therapy who presented with symptoms of acute abdomen with minimal low back symptoms. No intraabdominal process was found by abdominal studies and exploratory laparotomy. Increased lower back symptoms led to further skeletal spine studies, which initially demonstrated a compression fracture at the twelfth thoracic (T12) vertebra. Later, a T8 and a fourth lumbar (L4) compression fracture were also found. Her abdominal and lower back symptoms resolved on conservative therapy. Although the rate of these occurrences are unknown, compression spine fractures should be considered in elderly patients presenting with acute abdomen after being on long-term corticosteroid therapy. PMID- 2213917 TI - Tardive dyskinesia successfully treated with alprazolam. AB - Tardive dyskinesia is a disorder secondary to prolonged treatment (from 18 months to 3 years) with antipsychotic agents, affecting approximately 15% to 20% of patients. Tardive dyskinesia is characterized by difficulty controlling involuntary movements of the small muscle groups, producing tic-like reactions, muscle rigidity, and difficulty maintaining muscle tone. It is a chronic and unrelenting disorder which may be permanent if not successfully treated. The mechanism of action is thought to be secondary to dopamine hypersensitivity resulting from prolonged deprivation of dopamine on the part of dopamine sensitive receptors. Theoretically, these receptors have been deprived of the neurotransmitter by chronic treatment with antipsychotic drugs, which are recognized as dopamine-blocking agents. We present a case in which alprazolam was successfully used in treating tardive dyskinesia. PMID- 2213918 TI - Selenium status in workers handling aromatic nitro-amino compounds in a chemical factory. AB - The selenium status of workers handling aromatic nitro-amino (ANA) compounds was evaluated by measurement of their blood and urinary selenium concentrations and blood glutathione peroxidase (GSH-Px) activities. Forty-seven healthy Japanese male workers (42.7 +/- 12.1 yr) handling ANA compounds routinely in a chemical factory were studied as exposed workers, and 107 nonindustrial healthy Japanese males (39.3 +/- 10.0 yr) in the same region served as a control group. Urinary diazoreaction-positive metabolites and methemoglobin, both of which have been used as indices of exposure to ANA compounds, were significantly elevated in the exposed workers. Both plasma and erythrocyte selenium in the exposed workers showed 20% lower values compared to the control group. GSH-Px activities in plasma and erythrocytes were also significantly decreased in the exposed workers, but urinary selenium excretions were similar between the two groups. Questionnaire information obtained from each subject regarding intake habits of selenium-rich foods (bread, eggs, meat, and fish) indicated that the average dietary selenium intake was similar for the control group and the exposed workers. These results indicate that (1) the workers handling ANA compounds were surely exposed to these chemicals; (2) their selenium status was lower than that of the nonindustrial controls; and (3) the low selenium status was not associated with any dietary factor. PMID- 2213919 TI - Urinary mutagens in municipal refuse incinerator workers and water treatment workers. AB - Municipal refuse incineration workers may be exposed to mutagenic compounds from gaseous and particulate emissions and during ash removal operations. The frequency of urinary mutagens was measured by the Ames test among a sample of 104 refuse incinerator workers in seven incinerator plants during March-May 1988. The frequency was compared to that observed in 61 water treatment employees in 11 municipal water treatment facilities during the same period. Incinerator workers had a significantly higher risk for urinary mutagens and promutagens as compared to water plant workers after controlling for age. Among incinerator workers, increased risk of having urinary mutagens was associated with workers who wore protective clothing (defined as clothing other than masks or gloves) or whose job classification was equipment repair. It also showed a weak positive association with increasing age. There was an increased risk of urinary promutagens associated with not wearing gloves. The presence or absence of mutagenicity in workers' urine varied with plant location. Incinerator operating conditions affecting the production of toxicants and mutagens are discussed and the results of other studies involving toxicant exposure of humans near incinerators are cited. PMID- 2213920 TI - Effects of chlorine dioxide on the developing rat brain. AB - Male and female Long-Evans rat pups, exposed to an oral dose of 14 mg chlorine dioxide (CIO2)/kg/d (postnatal d 1-20), were examined for effects on brain development and for changes in thyroid activity. Body weight reductions were observed on postnatal (pn) d 11, 21, and 35. Forebrain weight and protein content were decreased on pnd 21 and 35, as were the DNA content on d 35 and the number of dendritic spines on cerebral cortical pyramidal cells, a marker for synapse formation. Otherwise, cell proliferation in the forebrain, cerebellum, and olfactory bulbs was normal, as were migration and aggregation of neuronal cells in three areas of the cerebral cortex. Histopathology of the forebrain, cerebellum, and brainstem showed no gross lesions, loss of myelin, or change in the cells staining positive for Nissl substance. Serum T3 and T4 levels, as well as hepatic mitochondrial alpha-glycerophosphate dehydrogenase activity, were unchanged by CIO2 treatment. The results indicated that CIO2 may have central neurotoxic potential. No underlying antithyroid activity was evident. PMID- 2213921 TI - Exposure to low levels of hydrogen sulfide elevates circulating glucose in maternal rats. AB - Although the lethal effect of hydrogen sulfide (H2S) has long been known, the results of exposure to low levels of H2S have not been well documented. Rat dams and pups were exposed to low levels of H2S (less than or equal to 75 ppm) from d 1 of gestation until d 21 postpartum and analyzed for changes in circulating enzymatic activity and metabolites. Blood glucose was significantly elevated in maternal blood on d 21 postpartum at all exposure levels. This increase in glucose was accompanied by a possible decrease in serum triglyceride in the pups and in the dams on d 21 postpartum. There was no evidence of alterations in serum alkaline phosphatase, lactate dehydrogenase, or serum glutamate oxaloacetate transaminase. PMID- 2213922 TI - Surface morphology and morphometry of rat alveolar macrophages after ozone exposure. AB - As the ultrastructural data on the effects of ozone on pulmonary alveolar macrophages (PAM) are lacking, transmission (TEM) and scanning (SEM) electron microscopy were performed on rat PAM present in alveolar lavages following exposure to ozone. Rats were continuously exposed for 7 d to ozone concentrations ranging from 0.25 to 1.50 mg/m3 for 7 d followed by a 5-d recovery period. Additionally, morphometry on lung sections was performed to quantitate PAM. In a second experiment rats were continuously exposed to 1.50 mg O3/m3 for 1, 3, 5, or 7 d. To study the influence of concurrent ozone exposure and lung infection, due to Listeria monocytogenes, rats were exposed for 7 d to 1.50 mg O3/m3 after a Listeria infection. The surface area of lavaged control PAM was uniformly covered with ruffles as shown by SEM and TEM. Exposure to 0.5 mg ozone/m3 for 7 d resulted in cells partly covered with microvilli and blebs in addition to normal ruffles. The number of large size PAM increased with an increase in ozone concentration. After 1 d of exposure, normal-appearing as well as many small macrophages with ruffles and scattered lymphocytes were seen. Lavage samples taken after 5 or 7 d of exposure showed an identical cell composition to that taken after 3 d of exposure. After Listeria infection alone, lavage samples consisted of mainly lymphocytes and some macrophages. Small quantitative changes, such as an increase in the number of polymorphonuclear neutrophils and large-size PAM, occurred in lavages after ozone exposure and infection with L. monocytogenes. Morphometric examination of lung sections revealed a concentration related increase in the number of PAM, even in animals exposed to 0.25 mg ozone/m3 for 7 d. Centriacinar regions were more severely affected than other regions of lung tissue. By 5 d after termination of exposure to ozone, the number of lysozyme-positive alveolar cells was still significantly increased in centriacinar areas of the lung. The results indicate that ozone exposure causes major changes in the number, size, and surface morphology of PAM in rat lung. Furthermore, the results presented here suggest that changes in alveolar macrophage function are reflected by morphological changes. PMID- 2213923 TI - Inhibition of replicative DNA synthesis and induction of DNA repair in human fibroblasts by the intercalating drugs proflavine and 9-aminoacridine. AB - The induction of unscheduled DNA synthesis (UDS) and the alteration of semiconservative DNA replication by the structurally related intercalating agents proflavine and 9-aminoacridine were studied in MRC-5 human fibroblasts in culture. Autoradiographic determinations of both parameters were carried out simultaneously in the same culture specimens. Proflavine affected DNA synthesis, but did not elicit any UDS. 9-Aminoacridine inhibited DNA synthesis only at the highest concentration and caused UDS to a low but significant extent. These results suggest that the ability to induce UDS is not a general property of the intercalating agents and that the alterations of the DNA structure, typical of the "pure" intercalative process, are not handled by pathways involving unscheduled synthesis. PMID- 2213924 TI - Chlorinated hydrocarbon insecticides in Colorado beef cattle serum--a pilot environmental monitoring system. AB - A pilot project was initiated to test an existing animal disease surveillance system for use in monitoring environmental pollutants. Eleven chlorinated hydrocarbon insecticides were assayed to provide an indication of environmental contamination. A total of 241 bovine serum samples from 53 Colorado beef ranches was tested; 123 samples (51%) were found to contain detectable concentrations of 1 or more of 11 chlorinated hydrocarbons. There were a total of 203 occurrences of a compound being found at a level exceeding the detection limit. Heptachlor, heptachlor epoxide, lindane, and oxychlordane were the insecticides detected most frequently in bovine sera. This pilot study supports the use of domestic food producing animals as sentinels of environmental contamination with insecticides. PMID- 2213925 TI - Effect of acute exposure to boric acid on the male reproductive system of the rat. AB - Adult male rats were dosed orally on d 0 with 0 or 2000 mg/kg of boric acid and killed on posttreatment d 2, 14, 28, and 57, or dosed with 0, 250, 500, 1000, or 2000 mg/kg of boric acid and killed on posttreatment d 14. At d 14, atypical structures that appeared to be enlarged irregular cytoplasmic lobes of Step 19 spermatids were observed in Stage VIII seminiferous tubules of rats dosed with 1000 and 2000 mg/kg. Abnormal retention of Step 19 spermatids and residual bodies was also observed in Stage IX-XIII tubules of these rats. The retained spermatids and residual bodies were seen in both the luminal and basal regions of the epithelium. A substantial increase in the testicular sperm head count occurred in animals dosed with 2000 mg/kg. Abnormal caput epididymal sperm morphology and reduced caput epididymal sperm reserves were observed at 1000 mg/kg and higher. Serum LH, FSH, TSH, and prolactin values were not affected at any dosage. At d 28, rats dosed with 2000 mg/kg exhibited continued retention of Step 19 spermatids into Stage X, abnormal caput and cauda sperm morphology, and decreased percentages of motile cauda spermatozoa with reduced straight-line swimming velocities. By d 57 substantial recovery was apparent; some retention of Step 19 spermatids into Stage X tubules was still present in two out of six rats but the sperm parameters were comparable to controls. The study indicated that acute oral exposure to boric acid adversely affected spermiation and sperm quality in the adult male rat. At the dosages used the effects appeared reversible. The no effect level was 500 mg/kg. PMID- 2213926 TI - Effects of trifluoroacetic acid, a halothane metabolite, on C6 glioma cells. AB - Effects of trifluoroacetic acid (TFA) on cell growth, DNA, glycoprotein, and dolichol-linked oligosaccharides synthesis and ribonucleotide triphosphate concentrations were examined in exponentially growing C6 murine glioma cells. One day of treatment with TFA caused a slight concentration-dependent enhancement of cell growth and [3H]thymidine incorporation. Exposure for 1 or 5 d to TFA (0.5 7.0 mM) elevated the [3H]leucine incorporation in a dose- and time-dependent manner. The results suggested that TFA stimulated cell growth and enhanced protein synthesis. TFA also affected [3H]mannose incorporation into glycoproteins and dolichol-linked oligosaccharides in a dose-dependent fashion. In addition, it was found that TFA accelerated lectin-induced cell agglutination. These data suggest that TFA, the principle halothane metabolite, alters plasmalemmal glycoprotein synthesis. These findings should form a basis for further understanding on the mechanism underlying halothane-associated neurotoxicity. PMID- 2213927 TI - Factors affecting levels of DDT and metabolites in human breast milk from Kwazulu. AB - Concentrations of p,p'-DDT, p,p'-DDE, and p,p'-DDD have been determined in breast milk of mothers residing in two different areas of KwaZulu. Annual intradomiciliary application of DDT was used for the interruption of malaria transmission in one area, while the other served as the control. Milk from mothers living in DDT-treated dwellings had significantly higher mean levels of DDT and metabolites (mean sigma DDT 15.83 mg kg-1 in milk fat) than those from the control area (0.69 mg kg-1). The highest recorded sigma DDT value was 59.3 mg kg-1 (milk fat). Primiparous mothers from the malarious area had significantly more sigma DDT and metabolites (sigma DDT 24.82 mg kg-1) than multiparous mothers from the same area (mean 12.21 mg kg-1). Parity was the best predictor of DDT in breast milk of the exposed group. The percentage DDT and the sigma DDT increased significantly with an increase in parity. The same, but not significant, trend was also found for the control group. It was hypothesized that the increase in percentage DDT that occurred with higher parities was due to the uptake of DDT and elimination via milk. This process was faster than the uptake and endogenous formation of DDE. Designing predictive models using multiple regression was not very successful. The recorded levels do not represent an appreciable health risk to the mothers. From the literature it was deduced that at the recorded levels, a well-founded risk to the infants, particularly the firstborns, exists in sprayed areas. PMID- 2213928 TI - Progress in characterizing anatomic injury. AB - A three-valued description of anatomic injury is presented. Anatomic profile (AP) components A, B, and C summarize serious injuries (greater than AIS 2) to the head/brain or spinal cord; to the thorax or front of the neck; and all remaining serious injuries. Relationships between AP components and survival rate reaffirm the seriousness of head injury. Logistic function models relating AP components and the Injury Severity Score (ISS) to survival probability were based on 20,946 Major Trauma Outcome Study (MTOS) patients (9.2% mortality rate) submitted through 1986. Model performance comparisons were based on 5,939 MTOS patients (7.8% mortality rate) submitted during 1987. The AP better discriminated survivors from nonsurvivors and provided a 31% increase in sensitivity when compared with the ISS. Neither the ISS nor the AP alone reliably predict patient outcome. The predictive power of methods for estimating patient survival probability which include physiologic indices or profiles, patient age, and an anatomic profile should be compared with current methods. The AP, which is based on the severity and location of all serious injuries, provides a more rational basis for comparing patient samples than the ISS. PMID- 2213929 TI - Injured drivers and alcohol use: culpability, convictions, and pre- and post crash driving history. AB - The culpability, crash-related traffic convictions, and pre- and post-crash driving records of a group of injured impaired (blood alcohol level greater than 80 mg/dl) drivers (N = 58) who were admitted to a Level I trauma center were compared with a group of admitted unimpaired drivers (N = 92). Both groups of drivers were 21 years of age or older, sustained moderate injuries (defined as having no injury of the brain, spinal column or cord, extremity, or pelvis with an Abbreviated Injury Score of greater than 2), and were discharged home. In the 140 crashes in which culpability was clearly defined, the impaired drivers caused a significantly greater percentage of their crashes (92.7%) compared to unimpaired (64.7%) drivers (p less than 0.001). Of the 55 unimpaired drivers who were considered culpable of causing their crashes, 12.7% received a traffic conviction compared with 39.2% of the 51 culpable impaired drivers. The mean number of total pre-crash traffic violations was higher for impaired drivers than for unimpaired drivers (p less than 0.01). While the mean number of total post crash convictions for unimpaired and impaired was not significantly different, the mean number of pre- and post-crash alcohol convictions was significantly higher for impaired drivers compared to unimpaired drivers (p less than 0.02). The data suggest that injury protects from legal prosecution and does not alter impaired driving practices. PMID- 2213930 TI - The effect of prehospital fluids on survival in trauma patients. AB - The effect of prehospital intravenous fluids upon survival was studied in 6,855 trauma patients. Mean prehospital time was 36 minutes in both the group of patients who received fluids and the group that did not. The volume of fluid administered was not significantly different in the group who survived compared to those who died. Eighty-five per cent of the patients had an Injury Severity Score (ISS) less than 25 and the mortality rate in the 56% of patients in this group who received fluids was similar to that of the patients who did not receive fluids (0.7% vs. 0.5%). Twelve per cent of the patients had an ISS between 25 and 50. Sixty per cent of these patients received fluids and the mortality rates were similar to the patients who received fluids compared to those who did not (23% vs. 22%). Three per cent of patients had an ISS of greater than 50 and the mortality rate was highest in this group but was not influenced by the administration of fluids (90% vs. 86%). Comparison of groups with similar probability of survival according to the TRISS methodology also failed to show an influence of fluid administration on survival. The mortality rate in patients with an initial systolic blood pressure (BP) of 90 torr or greater was compared to the rate in patients with an admission BP less than 90 torr. Although hypotension was associated with a significantly higher mortality rate, the administration of fluids had no influence on this rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213931 TI - The prophylactic use of antibiotic impregnated beads in open fractures. AB - Four hundred four compound fractures were reviewed in 339 patients treated between August 1983 and November 1987. The 252 males and 87 females had a mean age of 33 years (range, 14-86). One hundred twenty-seven (31.4%) fractures were classified as Grade I, 153 (38.9%) as Grade II, and 124 (30.7%) as Grade III by Gustilo's classification. The mean Injury Severity Score was 15 (range, 9-57). Three hundred thirty-four of the open fractures (82.7%) were managed with antibiotic-impregnated bead chains (tobramycin) and systemic antibiotic prophylaxis (cefazolin, tobramycin, and penicillin). Seventy open fractures (17.3%) received systemic antibiotic prophylaxis (cefazolin, tobramycin, and penicillin) without supplemental use of the antibiotic beads. All open fractures underwent acute irrigation and debridement. In the 404 fractures 46.5% of wounds were closed primarily, 12.9% underwent delayed primary closure, 7.9% were left open, and 32.7% were temporized by the antibiotic bead pouch technique until definitive flap coverage and skin grafting were performed. Of the 404 fractures evaluated, 17 (4.2%) developed an acute wound infection. Of these wound infections, eight (11.4%) were in the group managed with systemic antibiotics alone. By comparison, nine (2.7%) of open fractures treated with combined systemic antibiotics and antibiotic-impregnated beads developed an infection. Chronic osteomyelitis developed in 18 of 404 open fractures (4.5%). Ten (14.3%) open fractures which developed osteomyelitis were managed with systemic antibiotics whereas eight (2.4%) fractures managed with systemic antibiotics and antibiotic-impregnated beads developed a chronic infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213932 TI - Blunt trauma in adults and children: a comparative analysis. AB - Trauma remains the major cause of death in children and young adults. Adult and pediatric patients differ significantly in both mechanism of and physiologic response to injury. We reviewed the records of all consecutive adult and pediatric blunt trauma patients admitted to a major metropolitan trauma center for a 10-year period. An extensive computerized database has been maintained for all patients since 1977. A comparative statistical analysis of mechanism of injury, specific organ injury, and clinical outcome was performed. Altogether, 1,722 adults and 289 children were treated during the study period. Blunt trauma accounted for 82.8% of adult and 94.3% of pediatric injury (p = 0.00005), and only these patients were considered for analysis. Diagnostic peritoneal lavage was performed in 249 children and 1,464 adults, with a respective accuracy of 99.6% and 97.2%. Mechanism of injury was comparable for both groups, although children were far more likely to be injured by falls, bicycle accidents, or struck by an automobile. Comparative analysis of specific injuries demonstrated significantly fewer pediatric chest (p = 0.001), spine (p = 0.03), and pelvic (p = 0.003) injuries. Central nervous system (CNS) injury in children was a strong determinant of outcome: serious pediatric CNS trauma was associated with a tenfold increase in mortality. Mortality for children in the absence of CNS injury was less than 3%. Spinal injury also appeared to be a predictor of poor outcome in the pediatric population, with an associated mortality of greater than 50%. Overall, survival was age independent (82.5% of adults and 85.8% of children were survivors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213933 TI - Alcohol intoxication, injuries, and dangerous behaviors--and the revolving emergency department door. AB - Suicides, homicides, motor vehicle crashes, and other violent deaths and injuries are linked inextricably to alcoholism. The association of injury and alcoholism should be particularly obvious to Emergency Department (ED) physicians. We sought to determine the extent to which intoxicated patients in an ED were properly diagnosed, counselled, and referred for substance abuse care. We reviewed the charts of 153 consecutive patients seen in a teaching hospital ED who had blood alcohol levels above 100 mg%. Most were male (70%), white (62%), young (mean age, 34 years) and severely intoxicated (mean BAL, 245; range, 109-558 mg%). Forty-six per cent of visits were for trauma; half of the patients were victims of violent assaults. The intoxicated patients received extensive medical and surgical management: an average of five tests or X-rays were performed per patient; 75% received at least one medication; at discharge 48% were referred for followup to medical or surgical clinics. In contrast, few patients were evaluated for dangerous behaviors or referred for treatment of alcoholism: only 19 patients (12.5%) were asked about depression, suicide, or homicide; 15% were advised to stop drinking; 13% received a referral to a psychiatrist, mental health worker, or alcohol rehabilitation facility. Forty-seven per cent of patients received "stat" intravenous thiamine (although the Wernicke-Korsakoff syndrome is rare). In contrast, only 16% received a stat on-site psychiatric consultation (although dangerous behaviors are common in alcoholics). There was a strong, statistically significant negative association between the occurrence of an injury and the decision to initiate treatment and referrals for alcoholism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213934 TI - Oxygen delivery and consumption in head-injured and multiple trauma patients. AB - Critically ill patients often demonstrate that whole body oxygen consumption (VO2) is dependent on oxygen delivery (DO2). In this retrospective study, the relationship of VO2 to DO2 in patients with isolated head injury (HI, n = 18) was compared to that in patients with multiple trauma (MT, n = 60) without serious head injury. Mean pulmonary capillary wedge pressure, central venous pressure, arterial PCO2, cardiac index, and oxygen delivery were significantly lower in HI, but oxygen consumption was not different in the groups. In both groups, changes in DO2 (delta DO2) within each patient were significantly correlated with changes in VO2 (delta VO2) in that same patient. This relationship was not different between the HI patients, (delta VO2 = (0.20 +/- 0.02) delta DO2), and the MT patients (delta VO2 = (0.17 +/- 0.01) delta DO2). When these groups were further divided into those with high hematocrit (greater than 32%) and low hematocrit (less than 32%), HI patients with a low hematocrit demonstrated a steeper regression slope, with 26 +/- 3% of the DO2 change being reflected in the VO2 change. This was significantly greater than the slope in HI patients with high hematocrit (13 +/- 3%) and the MT patients at high (19 +/- 2%) or low (16 +/- 2%) hematocrits. These data show a correlation between changes in oxygen delivery and consumption that is similar in both head-injury patients and multiple trauma patients without serious head injury. This relationship was greatest in head injured patients at low hematocrit. This relationship of VO2 and DO2 in both groups suggests an influence of neurohumoral factors rather than local tissue phenomena.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213935 TI - Splenectomy influences endotoxin-induced bacterial translocation. AB - To determine whether splenectomy affects the antibacterial defenses of the gut, experiments were performed using bacterial translocation (BT) as a marker of intestinal barrier failure. The incidence of BT was measured 8 days after splenectomy or sham-splenectomy in mice receiving or not receiving endotoxin (0.1 mg IP). Splenectomy does not appear to promote BT from the gut, since the incidence of bacterial translocation after splenectomy or sham-splenectomy (5%) were not different. A second experiment was performed to determine whether the resistance to endotoxin-induced BT was modified after splenectomy. The incidence of endotoxin-induced BT was 73% in the unoperated control group, 59% in the sham splenectomy group, but 23% in the splenectomy group (p less than 0.002). Thus, splenectomy but not sham-splenectomy increased the resistance of otherwise healthy mice to endotoxin-induced BT. PMID- 2213936 TI - Skeletal transfixation in treatment of comminuted fractures of the distal end of the radius in the elderly. AB - Ninety-five patients (71 females and 24 males), average age, 69 years (35-92 years), with comminuted distal radial fractures were treated with transfixation wires (Kirschner wires) through the bases of metacarpals II-V and an above-elbow plaster cast. Two cases of early infections and four of Sudeck's dystrophy (4.2%) were encountered. Followup studies which lasted an average of 24 months (9-50 months) could be conducted on 77 patients. Using Sarmiento's ratings 27 patients fell into the very good category, 44, good, eight, fair, and two, poor. Although most of the cases were of the comminuted intra-articular fracture types, good results were achieved with this simple and quite straightforward method. PMID- 2213937 TI - A reassessment of the peritoneal lavage leukocyte count in blunt abdominal trauma. AB - Nine hundred and three patients undergoing diagnostic peritoneal lavage (DPL) over a 6-year period were retrospectively reviewed to evaluate the utility of the white blood cell (WBC) count in the lavage fluid. Eleven patients (1.2%) had dialysate WBC counts greater than 500/mm3, with erythrocyte counts less than 10(5)/mm3. Nine of these patients who were lavaged within 4 hours of injury had no intra-abdominal pathology. Two patients, lavaged after 4 hours, demonstrated intra-abdominal injury. Two hundred twenty-three patients (24.7%) had grossly clear dialysate which was not sent for laboratory analysis. None of these patients required laparotomy. We conclude that the WBC count in DPL fluid is of no diagnostic value in victims of blunt abdominal trauma who are lavaged within 4 hours of injury. In addition, laboratory analysis of clear dialysate is not required in these patients. PMID- 2213938 TI - Analysis of 46 intra-abdominal aortic injuries from blunt trauma: case reports and literature review. AB - Blunt trauma causing aortic injury is infrequent and primarily involves the thoracic aorta. Abdominal aortic injury after blunt trauma is much less frequent and has a varied presentation. Within a 3-month period, our trauma unit diagnosed and treated two cases of abdominal aortic injury secondary to blunt trauma. One was a belted passenger in a motor vehicle accident, and one was secondary to a crush injury. The addition of these two cases brings the number found in the literature to 46. Reviewing these cases has emphasized the need for prompt recognition and treatment of this vascular catastrophe. PMID- 2213939 TI - Concerning a blind-eyed view of the trauma patient impaired by alcohol. PMID- 2213940 TI - The debate goes on. PMID- 2213941 TI - Reduced dependency on arteriography for penetrating extremity trauma: influence of wound location and noninvasive vascular studies. AB - Indications for arteriography in penetrating extremity trauma remain controversial. We reviewed our clinical experience in 454 patients (514 extremities) with penetrating trauma admitted during a prior 3 1/2-year period. Injuries were caused by stab wounds in 60 (11.7%) extremities and by gunshot wounds in 454 (88.3%) extremities. Thirty-three of the 60 stab wounds (55%) required urgent exploration, and 27 underwent arteriography. No arteriograms were positive for unsuspected arterial injury in this group. Forty-two of 454 gunshot wounds (9.3%) underwent mandatory exploration; arteriograms were performed on 412 extremities. Forty-four arteriograms (10.7%) demonstrated evidence of unsuspected arterial injuries. During the last year, randomly selected extremities (n = 23) have been studied with B-mode ultrasonography and segmental Doppler pressure measurements. Using the subsequent arteriography as the "gold" standard, sensitivity was 83% and specificity was 100%. Gunshot wounds were categorized according to location and positive arteriograms. Injuries to the lateral thigh and arm resulted in no positive arteriograms, while positive studies were observed in 11% of medial and posterior arm, 14% of antecubital fossa, 25% of forearm, 7.5% of medial and posterior thigh, 8% of popliteal fossa, and 26% of calf injuries. We recommend arteriography for gunshot injuries to identified high risk areas, while clinical evaluation alone is accurate in all stab wounds to the extremities and gunshot wounds to the lateral thigh and outer arm. Preliminary data suggest expanded use of B-mode ultrasonography may further reduce our dependency on arteriography in these cases. PMID- 2213942 TI - The impact of volume on outcome in seriously injured trauma patients: two years' experience of the Chicago Trauma System. AB - The American College of Surgeons has stated that in considering the development of trauma systems it is important to ensure an appropriate volume of seriously injured patients be seen by each trauma center in order to achieve acceptable mortality rates. Clinical data supporting this recommendation are lacking. An analysis was performed on 1,643 seriously injured trauma patients to determine the relationship between volume and mortality rates. Three separate statistical methods were used: Pearson correlation coefficients, mortality odds ratios, and direct pairwise mortality comparisons. In addition, Tobit analysis was introduced as a method to analyze the relationship between volume and mortality. Mortality rates were adjusted for the confounding variable of serious head injury. Pearson correlation coefficients for volume vs. adjusted mortality was -0.65. Mortality odds ratios comparing the low-volume (less than 140 pts) trauma centers vs. the high-volume (greater than 200 pts) trauma centers was 1.3 for adjusted mortality rates (95% CI = 1.01-1.66; p = 0.04). Categorical analysis showed significantly different mortality rates in the centers before and after adjusting for patient mix. Tobit analysis showed the relationship between volume and mortality to be significant, accounting for 30-40% of the observed variation in mortality rates. In addition, Tobit analysis allowed construction of a model to predict mortality rates, given specific volumes of patients. Our data suggest that an inverse relationship exists between volume and mortality, and support the necessity of configuring trauma systems in a manner that will ensure designated trauma centers will see a high volume of seriously injured patients. PMID- 2213943 TI - Acute hospital costs of trauma in the United States: implications for regionalized systems of care. AB - As part of a larger effort to determine total direct and indirect costs of injury in the United States, national estimates of the numbers and expenditures associated with acute hospitalization due to traumatic injury were derived using data from the 1984, 1985, and 1986 National Hospital Discharge Surveys (NHDS). Estimates of the numbers of hospital episodes and total expenditures are reported in this paper for subgroups of patients defined by age, sex, and body region and AIS severity of the injuries sustained. In 1985 2.1 million individuals sustained a traumatic injury which resulted in hospitalization. Hospital expenditures totaled $11.4 billion inclusive of professional fees. Adolescents and young adults aged 15-44 years accounted for nearly one half of all discharges and total hospital costs. The elderly, who represent only 12% of the population, accounted for an additional one quarter of total discharges and hospital costs. Nearly three quarters of the hospitalizations and one half of total expenditures were for minor (ICD/AIS = 1, 2) injuries. Moderate (ICD/AIS = 3) and severe (ICD/AIS = 4, 5), injuries respectively accounted for 23% and 3% of total episodes and 37% and 11% of total expenditures. Only 12% of patients and 25% of trauma care dollars involved injuries sufficiently severe to require treatment at a trauma center.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213944 TI - Endotoxin (LPS) increases mesenteric vascular resistance (MVR) and bacterial translocation (BT). AB - Endotoxemia is responsible for many of the pathophysiologic alterations that occur with Gram-negative sepsis. We utilized a chronic ovine model to determine the hemodynamic disturbances in the gastrointestinal tract during endotoxemia. Sheep with indwelling arterial, venous, and pulmonary arterial catheters were used. An ultrasonic flow probe was placed on the cephalic mesenteric artery. The animals were subjected to: 1) Ringer's lactate infusion (sham n = 6); or 2) 1.5 mcg/kg E. coli endotoxin (n = 6) over over a period of one half hour and were monitored for 48 hours. They were then sacrificed and specimens of mesenteric lymph node, liver, spleen, kidney, and lung obtained for bacteriologic cultures and histologic analysis. Sheep receiving endotoxin showed more than 50% reduction in the mesenteric blood flow. Mesenteric vascular resistance increased while non mesenteric systemic vascular resistance decreased. The increase in the total systemic vascular resistance, noted during endotoxemia, was thus likely due to the increase in the mesenteric vascular resistance. At autopsy there were positive cultures for microorganism in the mesenteric lymph nodes in six out of six sheep with endotoxemia as compared to one out of six of control. Thus the vasoconstriction in the mesenteric areas may have resulted in bacterial translocation from the GI tract. PMID- 2213945 TI - Geographic patterns of urban trauma according to mechanism and severity of injury. AB - The purpose of this study was to investigate the distribution of various mechanisms of injury and the relative severity of such injury cases throughout the different geographic zones of a large urban area using a computerized emergency medical services (EMS) dispatch/patient record database. The study city (population, 2 million residents) was divided into 156 geographic grids (each 4.5 by 3 miles) and the incidence and relative severity of various injury mechanisms were determined for each zone. RESULTS: In one year (1988), there were more than 115,000 separate EMS incidents involving more than 150,000 patients, 26,000 of whom were transported for injuries incurred in 10,064 motor vehicle accidents, 4,587 falls, 4,015 lacerations/stabwounds, 1,796 beatings, 1,270 gunshots, and 952 auto-pedestrian accidents. Analysis of the 156 zones showed a disproportionate number of EMS responses in the city center with two centralmost grids accounting for about 25% of all responses. Call volume then progressively diminished toward the periphery of the city. However, with some very minor exceptions, the relative incidence and severity of the various injury mechanisms remained proportionally uniform within each zone, regardless of geographic location. Therefore, contrary to popular notoriety, the incidence and associated severity of any given injury type generally was not necessarily predicted by any particular neighborhood predilection for it, but rather by the overall demand for EMS in that zone of the city. PMID- 2213946 TI - The lap belt complex: intestinal and lumbar spine injury in children. AB - The "seatbelt syndrome" describes intestinal and spinal injury caused by lap style automotive restraints. More than 2,600 children were admitted to Children's National Medical Center with blunt injury in 3 years; 395 were involved in a motor vehicle crash. Ninety-five of the crash occupants (24%) were known to be wearing safety belts. Ten children sustained a "lap belt injury": five with lumbar spine injury, four with combined lumbar spine and intestinal injuries, and one child with intestinal injury. All ten children presented with a characteristic transverse abdominal ecchymosis. The CT scan was unreliable in evaluation of both spinal and intestinal injury. Lateral radiographs were required for definitive diagnosis in eight of nine children with lumbar spinal injury. CT scan was clearly diagnostic in only one of five children with intestinal injury. Children wearing lap belts are at risk of a "lap belt complex." Lateral spine X-rays, peritoneal lavage, and early laparotomy are recommended to establish an accurate diagnosis and to decrease morbidity. PMID- 2213947 TI - Alternative delivery system for controlled drugs in the surgical intensive care unit. AB - Faced with a serious shortage of qualified nurses for critically ill patients, methods to reduce the time required to deliver care without sacrificing quality are needed. A non-electronic device designed as a patient-controlled analgesic (PCA) was evaluated as a nurse-controlled device (NCA). Twenty-five intubated patients received morphine sulfate (MS) with the nurse-controlled device (NCA) and 12 by standard IV push policy. The average nursing time for narcotic dosing with the standard policy was 5 minutes/unit dose. A total of 1,183 NCA doses were given over 77 patient days. The average doses per patient day were 15 (2-38). The average nursing time was 22 seconds/NCA dose. The NCA saved 85 nursing minutes/patient day. Annual nursing labor costs were reduced by $77,000.00 with NCA. Total costs for standard IV push narcotic use were $36.43/patient day versus $35.45/patient day for NCA. Using this protocol, the NCA system saved $8,500.00 annually. By increasing the duration of PCA use to 72 hours, the annual savings would become $49,500.00. These data indicate that a simple NCA can deliver controlled drugs rapidly and safely, save valuable nursing time, and decrease the cost of ICU care. PMID- 2213948 TI - The role of antibiotic therapy in the prevention of empyema in patients with an isolated chest injury (ISS 9-10): a prospective study. AB - The purpose of this study was to determine the impact of an antibiotic regimen on the incidence of empyema in patients admitted with isolated chest trauma (ISS 9/10) and hemopneumothorax requiring tube thoracostomy. All patients with isolated chest trauma and hemopneumothorax (estimated ISS 9 or 10) seen in our trauma center were considered eligible for this study. Patients were excluded for the following reasons: age less than 18 years, presence of shock at the time of initial resuscitation, ongoing antibiotic therapy for unrelated disease, documented pre-existing infection or documented abnormal immune status. Ninety patients were randomized to two treatment limbs: antibiotics and tube thoracostomy or tube thoracostomy alone. All patients had the procedure performed in the trauma center in a standard fashion. Wound care and tube care were identical. Antibiotic therapy consisted of a first-generation cephalosporin (cefazolin), one dose given just before the procedure and then q 6 h into the tube removal. Injury Severity Scores were established as described by Schwab after the manner of Baker. Statistical analysis was performed using Fisher's exact test of binary outcome. In this study, antibiotics were able to reduce the incidence of empyema in patients with isolated chest trauma and for such patients antibiotic treatment appears justified. Further work is required to determine the effect on patients with more severe injury and multisystem involvement. PMID- 2213949 TI - Management of complex perineal soft-tissue injuries. AB - Debridement, fecal diversion, and rectal washout have been proposed as the primary therapy for complex perineal lacerations, but, in most series, survivors have a pelvic sepsis rate of 40-80%. In a retrospective study, six of 18 patients sustaining severe perineal lacerations died within the first few hours of injury due to exsanguination from pelvic injuries. The remaining 12 patients underwent sigmoidoscopy, diversion of the fecal stream with irrigation of the distal rectal stump, and radical initial debridement of necrotic soft tissue. Enteral access was obtained in two patients. In the patients with mandatory daily debridement and pulsatile irrigation, no pelvic sepsis occurred. In three patients without daily debridement, pelvic sepsis complicated recovery. The ability of patients to resume oral nutrition was significantly delayed, necessitating total parenteral nutrition in three patients. We conclude that sigmoidoscopy, total diversion of the fecal stream with irrigation of the distal rectal stump, enteral access for feeding, radical initial debridement of necrotic soft tissue, and mandatory daily debridement with pulsatile irrigation optimize recovery from this devastating injury. PMID- 2213950 TI - Intra-abdominal and retroperitoneal organ injuries diagnosed on dynamic computed tomograms obtained for assessment of renal trauma. AB - The efficacy of dynamic computed tomography in assessment of renal, intra abdominal, and retroperitoneal organ injuries is analyzed in some 444 patients. This technique contributed most valuable information toward the diagnosis of such coexistent injuries in patients who sustained blunt trauma. CT identified associated abdominal or retroperitoneal organ injuries in 85% of the patients (277 of 324), clinical examination in only 26%. CT proved invaluable for assessment of injury to bowel and mesentery, pancreas, and retroperitoneal vascular structures, giving rise to hematomas. CT diagnosed all such injuries, clinical examination from 0% (pancreas) to 11% (retroperitoneal hematomas). In patients with penetrating injury, dynamic CTs added valuable information on the status of viability of the injured organs. A relatively high number of false positive diagnoses resulted in only four unnecessary explorations. In all other patients, the erroneous diagnosis was revealed on repeat CTs undertaken because of inconsistency of the clinical course and clinical findings with the initially suggested CT diagnosis or at time of exploration undertaken for correction of other confirmed injuries. Discovery of associated intra- or retroperitoneal organ injuries, particularly in patients who sustained blunt trauma, has resulted in modification of treatment which prevented late sequelae and complications and thereby substantially reduced hospitalization time. PMID- 2213951 TI - Traumatic rupture of the aorta--critical decisions for trauma surgeons. AB - The diagnosis and initial stabilization of patients with traumatic rupture of the aorta (TRA) is performed by trauma surgeons. The resuscitations of 54 TRA patients at a Level I trauma center are reviewed. Although the survival of patients who underwent attempted repair was good (75%), 21/27 (78%) deaths occurred during phases of treatment controlled by a trauma surgeon. The techniques and sequencing of resuscitation can affect outcome. Pneumatic antishock garments were not beneficial in the prehospital setting for patients with TRA. In fact, PASG were on and inflated in all patients who presented in cardiac arrest. Awake, unanesthetized intubation caused fatal aortic rupture in three patients. Pharmacologic control of blood pressure during intubation is necessary. The amount of fluid, blood transfusion, and changes in blood pressure secondary to therapy did not statistically affect outcome. The average time from arrival in the ER to angiogram was 64.7 minutes. The average time ER to operating room was 159.7 minutes. Seven cases of TRA had delayed diagnosis usually for a misinterpreted CXR (5/7). Delay in diagnosis did not directly contribute to any deaths. Associated abdominal injuries are a common cause of preventable deaths. Fourteen patients with combined abdominal injuries and TRA were identified. Four of six deaths occurred with potentially reparable injuries. Operative and diagnostic sequences must be adjusted to allow rapid control of all potentially fatal injuries. PMID- 2213952 TI - Cordyceps Sinensis-I as an immunosuppressant in heterotopic heart allograft model in rats. AB - To investigate the inhibitory effects of Cordyceps Sinensis-I (CS-1) on the immune response responsible for the organ transplant rejection, we studied its effects of prolonging heterotopic heart allograft survival on rat model with heart graft; the effects of CS-1 were compared with those of cyclosporine A and glucocorticoid, and the possible pathological changes caused by CS-1 were observed. Our results showed that CS-1 can prolong the survival of grafted heart without causing infection, and it did not exert detrimental effects on vital organs. As a result, it proves to be a promising immunosuppressant in clinical organ transplantation in the future. PMID- 2213953 TI - A comparative experimental study on primary and secondary nerve grafting following inferior alveolar nerve injury. AB - The damaged inferior alveolar nerve of rabbit was repaired with autogenous ipsilateral greater auricular nerve grafting primarily and secondarily, and electrophysiological, ultrastructural, microvascular and histochemical investigations were performed in this study. The results indicated that the experimental effects of group 1 out of 3 groups (group 1 with immediate grafting, group 2 with grafting after 4 weeks, and group 3 with grafting after 8 weeks) were the best and those of group 2 were second only to group 1 with no obvious difference between these two groups (P greater than 0.05). However, the results of group 3 were not good enough, and there was significant difference from the other two groups (P less than 0.05). Therefore, we were led to conclude that the injury should be repaired at once or within 4 weeks after inferior alveolar nerve was damaged, or within 2 or 3 months thereafter, to improve the function of the injured nerve as greatly as possible. PMID- 2213954 TI - A study on hepatitis D virus infection in liver tissues of patients with hepatitis B in China. AB - 2346 liver samples from 17 areas in China were investigated for intrahepatic hepatitis D antigen (HDAg) by direct enzyme-labelled technique. HDAg was detected in 167 out of 1764 samples of HBsAg positive individuals with the detection rate of 9.47%. Hepatitis D virus (HDV) infection existed in all the examined areas without any significant difference regarding HDAg detection rate. A relationship of intrahepatic HDAg to the pathologic type of the liver disease was observed. The HDAg detection rate in chronic liver diseases and severe hepatitis was higher than in other liver diseases. It suggested that HDV infection was associated with the progression and chronicity of the liver disease. Studies on the relationship between HDV infection and HBV replication showed that HBV replication might be suppressed by HDV infection. Both HDV and HBV, however, could replicate in the same hepatocyte simultaneously. PMID- 2213955 TI - The cytoplasmic HBVDNA implication: HBV replication or non-replicative status. AB - Intrahepatocellular HBVDNA was investigated in patients with chronic hepatitis B by in situ hybridization assay, employing biotin-labelled HBVDNA as the specific probe. It was found that HBVDNA was predominantly present in the cytoplasm of hepatocytes. In general the cases with cytoplasmic HBVDNA could be grouped as follows: 1) cytoplasmic HBVDNA coinciding with intrahepatic envelope protein and nucleocapsid component expression, this pattern of the cytoplasmic HBVDNA would be replicative; 2) cytoplasmic HBVDNA accompanied by intrahepatic single HBsAg expression, common to HBVDNA integrated into host genome with only HBsAg being found frequently in liver; 3) with only cytoplasmic HBVDNA, with neither HBsAg nor HBcAg expression, representative for non-replicative status. It is speculated that the reason for the occurrence of the cytoplasmic hybridization signal in cases with non-replicative HBVDNA may be due to DNA-RNA transcript hybrid. The prudent way to evaluate the implication of the cytoplasmic HBVDNA is to consider the combination of HBVDNA location, intrahepatic gene product expression, and HBV markers in the serum. PMID- 2213956 TI - Investigation on the relation of impedance rheopneumogram with pulmonary hemodynamics and right ventricular function in patients with chronic obstructive pulmonary disease. AB - In order to investigate the relation of impedance rheopneumogram with pulmonary hemodynamics and right ventricular function in patients with chronic obstructive pulmonary disease (COPD), we measured impedance rheopneumogram and performed right heart catheterization on 150 COPD patients simultaneously both at rest and during exercise test. The results showed that impedance rheopneumogram was mainly influenced by right ventricular after-load while the influences of right ventricular pre-load, right ventricular contractivity, right ventricular work index and cardiac output were rather slight. These results also suggest that in COPD patients impedance rheopneumogram is of great value when used to predict pulmonary arterial pressure but of little value when used to measure the right ventricular function. PMID- 2213957 TI - Human pituitary somatotroph adenoma and prolactinoma: an ultrastructural and immunoelectron microscopical study. AB - 17 cases of pituitary somatotroph adenoma and 38 cases of prolactinoma were studied with electron microscopy and immunoelectron microscopy using protein A gold complex. 4 adenomas were shown by immunoelectron microscopy to contain simultaneously growth hormone (GH)-producing and prolactin (PRL)-producing cells. 6 cases were classified as densely granulated GH adenomas and 11 as sparsely granulated variant, whereas only 3 adenomas out of 38 prolactinomas were identified as densely granulated adenomas. The present study showed that not all cells with fibrous bodies possessed secretory granules positive for GH, and in some cells with fibrous bodies PRL-producing granules were also detected. Misplaced exocytosis was found frequently in the sparsely granulated prolactinomas. From these findings it may be suggested that fibrous bodies are not a morphological feature characteristic of pituitary somatotroph adenomas. PMID- 2213958 TI - Microsurgical treatment of disorders of leg and foot--a report of 40 cases. AB - Since 1979, the authors have performed five types of microsurgical flap (including myocutaneous flap) graft to treat 40 patients with disorders of leg and foot. In the treatment of inflammatory diseases, good results were obtained owing to the following important points: 1) the operation was performed with inflammation well controlled or localized, particularly in chronic osteomyelitis; 2) indication for each type of microsurgical flap was made carefully; 3) isolation of flap was carried out gently, bleedings were thoroughly stopped by ligation. PMID- 2213959 TI - Orthotopic homotransplantation of vascularized composite mandibular tissue in rabbits immunosuppressed with cyclosporine A. AB - To develop the surgical model, composite mandibular tissue was transplanted at the same site. Revascularization was accomplished by end-to-end anastomosis of the facial vessels using standard microvascular techniques. A total of 33 vascularized composite mandibular tissue allografts were similarly performed between two incompatible strains of rabbit. In a control group of 9 animals, no immunosuppression was administered. All of these allografts were rejected acutely within 10 days after surgery. 7 allograft recipients were immunosuppressed with azathioprine and prednisone at 5 mg/kg.d and 2 mg/kg.d, respectively. Their allografts were also rejected acutely within 10 days. 17 allograft recipients were immunosuppressed with cyclosporine A (CsA). All allografts showed primary wound healing and hair growth and took on normal appearance. 8 of these recipients were given CsA at 5 mg/kg.d i.v. and their allografts were rejected at a mean time of 17.9 days. The remaining 9 recipients given CsA at 10 mg/kg.d i.v. rejected their allografts at a mean time of 36.1 days. In 3 of them, the rejection was reversed with CsA (20 mg/kg.d) injection for five days successfully, and one allograft survived more than 100 days. This pilot study suggests that the surgical model is reliable and that CsA will be useful as an immunosuppressive agent in the study of vascularized composite mandibular tissue allografts. PMID- 2213960 TI - [Bacterial flora of the external ear canal. 1. Cancer patients]. AB - The bacterial flora of the external ear canal was investigated in a group of 64 patients with head and neck cancer, to observe why otitis externa frequently occurs in cancer patients. Staphylococcus epidermidis (48.5%), Pseudomonas sp. (18.8%), and Flavobacterium sp. (16.8%) were the prominent isolates from ear samples, and Gram-negative organisms which rarely existed in normal canal, were found to be markedly increased (59.4%). Moreover, about half of all non-sterile ear canals were found to have more than one Gram-negative flora. We have concluded that cancer patients probably suffer from external otitis more frequently because of enhanced colonization by Gram-negative pathogens. PMID- 2213961 TI - Factors related to the willingness of nurses to care for AIDS patients in Taiwan. AB - Nurses' willingness to provide care for AIDS patients was studied using a self developed and evaluated anonymous questionnaire given to 258 nurses (a response rate 91.9%). The subjects were randomly sampled from three general hospitals in Taiwan and consisted of both nurses who have experienced providing care for AIDS patients and nurses who have not had the experience of caring for AIDS patients. As a result, 46.1% (119/258) of the nurses responded that they would accept caring for AIDS patient but 93.3% of them asked for extra pay as a condition. Among the 139 nurses who would refuse to care for AIDS patients, 48.2% of them would quit their jobs if giving such care was compulsory. The scores on knowledge of workplace risk and protection was higher among positive attitude nurses (p = 0.0031). The odds ratio (OR) estimation was elevated in those whose attitudes were positive (OR = 4.4; 95% CI 3.2-6.1) as compared to those whose attitudes were negative about willingness to care for AIDS patients. But no relationships were found in age, educational levels, years of practice, marital status, religious beliefs, position status, and experience in providing care for AIDS patients with a willingness to care for AIDS patient. We suggest that if nurses have a better knowledge of workplace risk and protection regarding AIDS, then they have a more positive attitude and a greater willingness to care for AIDS patients. PMID- 2213962 TI - Tuberculous spondylitis: a clinical analysis. AB - Twenty-seven tuberculous spondylitis patients were reviewed. Eighteen were men and 9 were women, the average age being 52 years. The lower thoracic and lumbar spines were involved most frequently. Fever, progressive pain over the involved spine and tenderness were common clinical manifestations. The neurological deficits were due to direct compression of neural structures by the inflammatory products. Elevated ESR and the Mantoux test were valuable indicators. About one fourth of patients had coexisting pulmonary tuberculosis. Therefore, tuberculous spondylitis must be considered first in cases with progressive backache, tenderness, fever, elevated ESR and positive Mantoux test. PMID- 2213963 TI - The role of serum-supplements in organ culture for pre-damaged corneal endothelium. AB - Thirty-six pig corneas were shaken in 0.18% NaCl to induce disseminated corneal endothelial damage. After treatment, the corneas were divided and cultured in 3 different combinations of media to study the effects of serum-supplements in corneal endothelial regeneration. There were MEM+10% FCS (FCS-group; n = 10); MEM+10% Nu-Serum (Nu-group; n = 10) and MEM only (control group; n = 16). After one week of culturing, most of the corneas in all 3 groups, despite the pre damage, kept intact endothelia. This means that the endothelia were repaired whether the sera were supplemented or not. The cell densities of each were 2,454 +/- 450 cells/mm2, 2,776 +/- 476 cells/mm2 and 2,627 +/- 558 cells/mm2 respectively. The differences between each group were statistically insignificant. The morphological findings were also without much difference. When considering the risk of serum induced hypersensitivity, FCS can be replaced by Nu Serum in the organ culture medium for corneal preservation. Since the advantage of serum-supplements in medium-term organ cultures seems limited, the necessity of serum supplements should be further reevaluated. PMID- 2213964 TI - Quantitative C-reactive protein in pulmonary infections. AB - A total of 207 cases were selected to evaluate the diagnostic value of C-reactive protein (CRP) in pulmonary infections. The mean +/- SD of CRP values in various pulmonary infections were as follows: 18.62 +/- 11.34 micrograms/ml for 32 cases of exudative-fibrotic tuberculosis; 15.98 +/- 16.66 micrograms/ml for 15 cases of tuberculous pneumonia; 25.61 +/- 18.96 micrograms/ml for 29 cases of tuberculous effusion; 16.66 +/- 10.18 micrograms/ml for 11 cases of tuberculous cavity; 81.1 +/- 24.9 micrograms/ml for 10 cases of miliary tuberculosis; 36.4 +/- 22.1 micrograms/ml for 19 cases of mycoplasmal pneumonia; 241 +/- 72 micrograms/ml for 38 cases of bacterial pneumonia; 225 +/- 65 micrograms/ml for 30 cases of bacterial pneumonia with effusion; 169 +/- 50 micrograms/ml for 16 cases of lung abscess. The CRP values of other pulmonary infections were as follows: 20.6, 20.8 micrograms/ml for two cases of Strongyloides stercoralis pneumonia; 7.4, 1.6 micrograms/ml for two cases of aspergilloma; 11.2, 12.4, 7.6 micrograms/ml for three cases of Pneumocystis carinii pneumonia. Serial changes in CRP values in 13 cases of well-treated bacterial pneumonia showed that values of CRP decreased to below half of the initial value on the 3rd to 4th day, and returned to about normal value on the 10th to 13th day. The study suggested that: a) various types of infections had different levels of CRP values, b) level of CRP values was determined both by the pathogen and the severity of inflammation, c) serial CRP values in bacterial infection could be used as a guide in treatment. PMID- 2213965 TI - [The individualized ANB angle of Chinese adults]. AB - The ANB angle is commonly utilized to determine sagittal jaw relationships in cephalometric analysis. The ANB angle may be affected by other factors; therefore, its correlation to another measurement should be further recognized. This will eliminate the possibility of a biased interpretation. The individual variation of the ANB angle was investigated in 80 lateral radiographic cephalograms. The sample consisted of 40 Chinese male and 40 Chinese female adults. All of the sample had neutral molar relationships (Class I), and balanced profiles; none had previously undergone orthodontic treatment. ANB, SNA, SN-MP angles and SN were calculated for each gender. Multiple regression analyses and regression equation were performed and established. The results indicate that the variation of the ANB angle can be explained by the variations of the SNA and SN MP angles. The males had less mandibular divergency than females (p less than 0.05); resulting in a different effective pattern. The derived equations are: ANBind = 0.42 x (SNA) + 0.31 x (SN-MP) - 41.1 for males; ANBind = 0.31 x (SNA) + 0.20 x (SN-MP) - 28.9 for females. The explanation power also showed gender difference: males 56.2%, females 24.2%. The ANB angle for different facial types are presented through equation-produced lists of individualized norms. These norms aid the interpretation of the individual variations. PMID- 2213966 TI - Correction osteotomy of flexion deformity of cervical spine in ankylosing spondylitis--a case report. AB - It is well known that severe flexion deformities of the spine may occur in patients suffering from ankylosing spondylitis. The prevention of these deformities by early recognition of the disease process should be the main aim of the medical profession in handling patients with specific spinal involvements. Yet, we still see all too often patients with advanced kyphotic deformities of the trunk who are very grossly disabled and thus present a major problem to definitive surgical correction of their deformities. Correction of rigid kyphosis by establishing a compensatory lordosis can be carried out in the lumbar or cervical area. Surgical intervention in the cervical region enables the chin to be lifted off the sternum, but great care has to be taken of the relatively bulky spinal cord, which practically fills the spinal canal. Excessive correction runs the risks of fatally damaging the nerves and vertebral vessels. Therefore, most centers perform correction osteotomies of the cervical spine progressively, with day-by-day adjustment of the external fixators. We present a case of cervical osteotomy in which, under local anesthesia and with the aid of S.S.E.P., cervical kyphosis was corrected by a one-stage procedure. The results and difficulties are described here-in. PMID- 2213967 TI - Effect of unilateral vagotomy on capsaicin-induced neurogenic inflammation in the trachea of rats. AB - This study reports the effect of unilateral vagotomy on neurogenic inflammation in the trachea. Neurogenic inflammation was produced in the trachea of vagotomized rats by a venous injection of capsaicin, the pungent ingredient of red pepper. Monastral blue was used as tracer dye to label the affected blood vessels. Vagus nerves and tracheal tissues were processed for light and electron microscopy. The damaged right vagus nerve was found to have degenerated. However, unilateral vagotomy did not completely block neurogenic inflammation in the trachea ipsilaterally and contralaterally, as shown in the whole mount preparations. Microscopic observations of tracheal tissue sections showed that neurogenic inflammation did not evenly occur on both sides of the trachea. The possible reason for this is discussed. PMID- 2213968 TI - V-Y advancement flap for facial defects. AB - V-Y advancement flaps based on subcutaneous pedicles are an ideal option for closure of small to medium sized facial defects. This technique has been used to treat 69 patients with various lesions of the face, (30 basal cell carcinoma, 9 squamous cell carcinoma, 18 nevus, 4 traumatic defect, 3 old scar and 5 others) during the past seven years. There was no necrosis of any single flap. All the designs could be planned so that the long axes of the flaps were parallel to the wrinkle line, contour line or line of dependency. All wounds healed uneventfully with fine or undelineated scar. There were no secondary operation for these cases. Clinical results of this series have shown advantages of this flap in reconstruction of facial defects. It is reliable in circulation and is easy to design and execute. It causes no distortion of critical features and offers excellent cosmetic satisfaction in color and texture matching. Therefore, the V-Y advancement flap is recommended for closure of properly selected facial defects. PMID- 2213969 TI - Prevalence of taeniasis and enterobiasis among aboriginal children in mountainous areas of Taiwan. AB - Children numbering 6,197 were tested for taeniasis. Those children were examined from May, 1981 to July, 1989. Sixty one primary schools, in eight mountainous districts provided the test group of children. The method used in these tests was the Scotch tape perianal swab. The overall infection rate of taeniasis was 1%. A total of 6,667 children were also examined for enterobiasis and the infection rate was 10%. There was no significant difference in the rate of taeniasis and enterobiasis by sex. The infection of taeniasis was highest in Tatung District (3%), Ilan County. However, there was no significant difference among the rates by district. The prevalence of enterobiasis was highest in Jenai District (17%), Nantou County and lowest in Lanyu District (2%), Taitung County. Taeniasis was not found among non-aboriginal school children, while 3% of aboriginal school children were infected with Taenia. However, the infection rate of Enterobius vermicularis among non-aborigines (39%) was much higher than that among aboriginal children (5%). These findings indicate that aboriginal children still eat raw meat and viscera of wild animals and acquire Taenia infection. PMID- 2213970 TI - Sequential changes of serum transaminase and abdominal sonography in patients with suspected dengue fever. AB - Southern Taiwan experienced a dengue (type 1) outbreak in the autumn of 1988. One hundred and thirteen febrile patients suspected as having dengue infection were seen in the emergency room of the Kaohsiung Medical College Hospital. These patients were recruited for this study. Two hundred and eighty-six sequential serum aspartate transaminase (AST) and alanine transaminase (ALT) data from these patients were analyzed. Data analysis showed serum AST had increased daily and all data were out of normal range from day 6 of the illness. Compared to the AST level on the first day of the illness, the AST level was noted to elevate to an average of 9.25 folds on day 6. The sequential changes of AST were as follows: AST had elevated since the third ill-day in most cases and reached a peak on the 7th or 8th ill-day. It then declined gradually from the 8th ill-day and became normal about 3 weeks later. The changes of ALT level were about the same as AST but had later onset and lower peak. Abdominal sonographic examinations showed thickening of the gall bladder wall, splenomegaly and ascites in some patients during acute stage of the illness and recovered completely after patients recovered from the dengue attack. The sequential change of serum transaminase levels and sonographic findings were compatible. These findings may be used as a reference for the differential diagnosis among dengue fever, acute hepatitis and acute cholecystitis. PMID- 2213971 TI - Time spent and satisfaction of new out-patients in Department of Internal Medicine. Kaohsiung Medical College Hospital. AB - To assess the time spent and the degree of satisfaction of new clinic patients, one hundred and nine new out-patients from the Internal Medicine Clinic of Kaohsiung Medical College Hospital were studied from January 30th to February 6th, 1985. Both accurate field recording and telephone interviews concerning the time spent for each procedure and satisfaction with the medical personnel and expense in their first visits were carried out. The total time spent was 152 +/- 65 minutes (mean +/- SD) from questionnaire and 126 +/- 56 minutes from field recording. According to field recording, time spent in waiting for registration was 39.8 +/- 42.9 minutes. Most (55%) of study patients spent more than one hour in waiting for consultation. The time spent in waiting for filling prescription was 17 +/- 6 minutes. The accessibility of the paramedical examination units was good. The degree of satisfaction was measured by a five point rating scale for series of questions. The response were "very satisfied" or "satisfied" with professional services but not medical expense and cashier attitude. According to our results, some of our attempts to innovate service have been done including an appointment system, colored directional arrowheads, and changing our schedule to opening 30 minutes earlier. PMID- 2213972 TI - [Comparative study on the pharmacokinetics and bioequivalence of two brands of norfloxacin preparation]. AB - The pharmacokinetics and bioequivalence of two norfloxacin, Gentle capsule and Baccidal tablet, were compared in eight healthy male volunteers. A 400 mg dose of norfloxacin was given orally after an overnight fasting to volunteers in a balanced two-way cross-over study. Blood samples were obtained at 0, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0 and 24.0 hours after the dosing. Norfloxacin concentration in serum was assayed by a high pressure liquid chromatographic method using an UV detector. All the data was processed by KMCP computer software and the pharmacokinetic parameters were calculated, based on one-compartment model. The results revealed that the maximal concentration (Cmax) of Gentle and Baccidal was 0.96 +/- 0.089 and 0.99 +/- 0.110; the time to reach maximal concentration (Tmax) was 2.0 +/- 0.0 for both; the elimination constant (Kel) was 0.101 +/- 0.006 and 0.098 +/- 0.005 hr-1; the elimination half life (T1/2, beta) was 6.909 +/- 0.483 and 7.094 +/- 0.350 hr; the absorption constant (Ka) was 2.444 +/- 0.188 and 2.490 +/- 0.096 hr-1; the absorption half life (T1/2, alpha) was 0.278 +/- 0.019 and 0.277 +/- 0.010 hr; the area under curve (from 0 to 12 hours) (AUC0-12) was 7.106 +/- 1.065 and 7.380 +/- 1.044 micrograms.hr/ml; and the area under curve (from 0 hour to infinity) (AUC0-infinity) was 9.183 +/- 1.257 and 9.550 +/- 1.300 micrograms.hr/ml respectively. There were no significant difference found between the two groups after statistical analysis with two-way ANOVA (p greater than 0.05). A series of statistical parameters including d%, delta, and 95% C.I. were calculated by a bioequivalence test computer software of Yamaoka Simi. In order to strengthen the statistical evidence, the power of the test (1 - beta) was also calculated. After evaluating all the parameters, there was no significant difference found between the two groups. Therefore, the high similarity of these two formulations is suggested by the authors. PMID- 2213973 TI - The variability of 24-hour, overnight 12-hour, and morning one-hour, urinary albumin excretion in normoalbuminuric and microalbuminuric hospitalized diabetics. AB - Albumin excretion rates (AER) of three consecutive days in different urine collection periods were measured in 7 hospitalized microalbuminuric diabetics (Ma DM) and 7 normoalbuminuric diabetics (Na DM). They were divided on the basis of an initial overnight urinary AER below or above 10 micrograms/min. The percentage of variation coefficients (% CV) of 24-hour, overnight 12-hour, and morning one hour urine collections in Ma DM were 29.9%, 31.8% and 50.9%, respectively; while in Na DM group were 60.0%, 60.3% and 74.5%, respectively. There was no significant difference in the variation of AER among the three different urine collection procedures in both Ma DM and Na DM groups, or for similar urine collection between the two groups. The initial AER was compared to the subsequent two AERs in overnight 12-hour collection. The results were that three Ma DM patients had a subsequent AER below 10 micrograms/min and two Na DM patients had a subsequent AER above 10 micrograms/min on a single occasion. Therefore, the high variability of both groups would be expected to result in category changes. Multiple urine collections are needed to detect the early diabetic nephropathy for the hospitalized diabetics. PMID- 2213974 TI - Taiwan's first case of perinatal transmission of HIV confirmed by a modified western blot test. AB - A 25-year-old Chinese woman, was found HIV antibody positive on December 14, 1988. During our follow-up, we tested her American husband and found him to be seronegative. Unfortunately, her six-month-old infant was seropositive. The standard Western blot test was used in the first stage of analysis. The bands which appeared on the infant's strip were p15, p24, p31, p55 and gp120/gp160, but using the modified Western blot test the bands which appeared were p15, p24, p31, gp41, p53, p55, p64 and gp120/gp160. All the bands appearing on the infant's strips which used a modified Western blot test had higher intensities than those of a standard procedure. The mother was apparently infected with HIV through intercourse with her ex-boyfriend, who was a European. AZT was given to the mother because her T4 cell count was 338 per microliter and because of persistent cervical lymphadenopathy. The infant, which was bottle-fed and had been delivered by caesarean section, may have become HIV infected during the uterine stage. PMID- 2213975 TI - Looking beyond child survival. PMID- 2213976 TI - The features of sickle cell disease in Saudi children. AB - Using a prospective and retrospective approach, the features of sickle cell disease (SCD) were investigated in 137 SCD children from the south-western region of Saudi Arabia. The patients were followed for a period of 2-5 years, during which period the severity of the disease was assessed and a 'severity index', was calculated for individual patients. The patients with SCD were classified into five groups based on the absence of thalassaemia (sickle cell anaemia, SCA), presence of beta zero-thalassaemia (HbS/beta zero-thalassaemia), SCA with alpha thalassaemia.2 [heterozygotes (-alpha/alpha alpha) or homozygotes (-alpha/alpha)] and S/beta zero-thalassaemia with alpha-thalassaemia. The results showed a high prevalence of associated alpha-thalassaemia and variable levels of HbF in these patients. SCA patients with associated alpha-thalassaemia (-alpha/-alpha) and S/beta zero-thalassaemia patients with one alpha-gene deletion had the highest values for haematological parameters and lowest values of red cell indices. No specific difference could be identified in the clinical manifestations in the different groups with the exception that long bone crisis and hand-foot syndrome were not encountered in patients with associated alpha-thalassaemia. The frequency of hepatomegaly and splenomegaly was also lower in this group. PMID- 2213977 TI - Childhood peptic ulcer disease in Jamaica. AB - Thirty-one children with peptic ulcer disease (PUD) were diagnosed in two major hospitals in Jamaica between 1979 and 1988. There were 21 girls and 10 boys with a mean age of 9 years. There were 26 duodenal ulcers and 5 gastric ulcers. Five patients (19 per cent) with a duodenal ulcer had a family history of peptic ulcer. Recurrent abdominal pain was the predominant presenting feature in 68 per cent and pain was present for a mean of 20 months. Bleeding occurred in seven patients (23 per cent). Twenty-nine patients were successfully treated medically. Two with duodenal ulcers required surgery. The majority of patients have remained well after a mean follow-up of 14 months. Although uncommon in children peptic ulcers should be considered in patients with recurrent abdominal pain. The majority will respond to medical treatment. PMID- 2213978 TI - The bacteriology of intra-abdominal abscesses in Nigerian children. AB - The bacteriology of intra-abdominal abscess in 30 Nigerian children showed anaerobic bacteria constituted 52 per cent of total microflora with Bacteroides fragilis and anaerobic streptococci (19 per cent each) being predominant. E. coli and S. aureus were the predominant facultative bacteria isolated occurring in 24 and 11 per cent, respectively. The incidence of abscess was higher in males than in females and these predominant bacteria were relatively resistant to penicillins, suggesting caution in the use of penicillins in the treatment of intra-abdominal infections. PMID- 2213979 TI - A simple system of nutrition surveillance for African communities. PMID- 2213980 TI - Causes of malnutrition in young children: Gilan, Iran. AB - Causes of malnutrition were investigated in agricultural area of Gilan, Iran. Family food availability and adult food intakes were adequate, but intakes of young children were deficient, in all socioeconomic groups, reflected in growth deficits. Associated factors were: late introduction and small quantities of solid food, poor maternal knowledge of child feeding, low dietary energy density due to rationing and high price of animal products, contamination of water supply, and use of sedative drugs. PMID- 2213981 TI - Neonatal mortality determinants in Jamaica. AB - The Jamaican Perinatal Survey included among its objectives the quantification of the island's neonatal mortality rate, the identification of the causes of these deaths (Wigglesworth Classification), and the determination of characteristics of both mother and infant that are associated with increased mortality. A death questionnaire was completed on babies who were born between September 1986 and August 1987, and who died in the neonatal period throughout the island of Jamaica. The neonatal mortality rate was 17.9 per 1000 live births with early and late rates of 16.0 and 1.9 per 1000, respectively. The major contributors to neonatal demise were prematurity and intrapartum asphyxia (74 per cent). Twins had a seven-fold greater risk of dying than singletons. Babies born to mothers under 15 years had a four-fold greater risk of dying than those of mothers 25-29 years. The neonatal mortality rate for Jamaica is high, with room for improvement, particularly in the prevention of perinatal asphyxia. PMID- 2213982 TI - Epidemiological survey of the enteropathogenic Escherichia coli isolated from children with diarrhoea. AB - Escherichia coli was isolated in 382 (94 per cent) of 406 children from 0 to 3 years of age who had been hospitalized for diarrhoea at the Hospital Municipal Salles Neto, Rio de Janeiro. Enteropathogenic Escherichia coli strains were isolated in 67 samples (18 per cent), distributed among the serogroups that were tested as follows: 0111 (33 per cent); 0125 (19 per cent); 0126, 0127, and 0142 (9 per cent); 0128 and 0119 (8 per cent); 055 (5 per cent); 0114 (2 per cent). No strains of EPEC belonging to serogroups 086, 0126, and 0158 were found. Among the samples in which EPEC strains were isolated, 15.0 per cent were children living in dwellings which had piped systems of water supply and drain, whereas with regard to those living in houses without such facilities, this percentage raised to 24 per cent. Similar results were found when the availability of water supply of drainage were taken separately. PMID- 2213983 TI - Patterns of breast feeding in western Ethiopia and their relationship to acute diarrhoea in infants. AB - To determine the extent of protection from breast feeding against acute diarrhoea, a cross-sectional study was conducted in rural areas in a western region of Ethiopia, Gamo-Gofa. The standard cluster sampling technique promoted by WHO/CDD Program was used. We employed trained and supervised health workers (physicians nurses, and sanitarians) as interviewers, and a pretested questionnaire was utilized for the purpose. Among a total of 3002 children under the age of 5 years surveyed for diarrhoeal disease morbidity, mortality, and treatment rates, all those 6 months of age and less (n = 331) were taken as subjects to examine the trends of breast feeding and their association with the occurrence of acute diarrhoeal diseases. It was found that out of these 331 infants, 217 (66 per cent) were exclusively breast-fed and 114 (34 per cent) were partially breast-fed. No one in the study group was fully weaned. Out of those who were exclusively breast-fed (n = 217), 25 (12 per cent) had diarrhoea which started within the past 2 weeks of the survey. Among those partially breast-fed (n = 114), 46 (40 per cent) had diarrhoea. The difference in the occurrence of diarrhoea among exclusively and partially breast-fed infants was statistically significant (P less than 0.0001). When infants with partial breast feeding were contrasted with those on exclusive breast feeding, a relative risk of developing diarrhoea of 5.2 (95 per cent confidence interval 3.00, 9.10) was obtained. It is recommended that breast feeding which tends to diminish with urbanization be promoted as one important intervention of the control of diarrhoeal diseases. PMID- 2213984 TI - The risk approach in preschool children suffering malnutrition and intestinal parasitic infection in the city of Sao Paulo, Brazil. AB - The association between parasitic infection and malnutrition in preschool children in the city of Sao Paulo, was studied according to degree of malnutrition, age, and income. Associations were assessed by risk analysis. Higher risks of malnutrition were found in children above 24 months of age infected with Ascaris, Trichuris or with more than three different parasites. The presence of more than three parasites per child affected nutritional status independently of income level. It is suggested that more attention should be given to intensity and chronicity of intestinal parasitic infection. PMID- 2213985 TI - Effect of ascariasis upon nutritional status of children. AB - One hundred children aged 24-72 months who had history of passing roundworms during the preceding 12 months were compared with 100 children without such history. The two groups were matched for age, sex, economic status, and birth order. Children who had ascaris were 2.1 cm shorter in height, 0.6 cm, thinner for mid-arm circumference, and 0.38 kg lighter in weight compared to the children who did not pass ascaris. The first two of these differences were statistically significant (P less than 0.005). It is concluded that: 1. ascariasis contributes significantly to malnutrition in communities where both coexist; 2. periodic deworming should form part of community nutrition programmes in areas where ascariasis is common; 3. future studies of a similar nature should include recording of height, arm circumference, and birth order. PMID- 2213986 TI - Association between weight for age and mid-upper arm circumference measurement: findings from Malawi. AB - Anthropometric methods involving measurement of weight-for-height, height-for age, weight-for-age, and mid-upper arm circumference have been extensively researched to identify an appropriate method of monitoring infant and child growth. Many countries have adopted weight for age as the main practical method. The Malawi Ministry of Health introduced weight for age based upon WHO recommended standards as a growth indicator in 1973. There are, however, difficulties in making the practice widely used at community level. In the present study, confined to the four urban areas of Malawi, a comparison was made between the weight-for-age (W/A) and mid-upper arm circumference (MUAC) measurements. A very good correlation was observed between the two methods of screening for identification of undernourished children from 4 months of age onwards. Correct use of MUAC was found to be as effective as W/A in detecting undernutrition. PMID- 2213987 TI - Doctor's declaration for breast feeding. PMID- 2213988 TI - Neonatal sepsis in Turkey: the comparison between penicillin plus aminoglycoside and ampicillin plus third-generation cephalosporin chemotherapies. PMID- 2213989 TI - The significance of socio-cultural factors in child malnutrition in urban Zambia. PMID- 2213990 TI - Breast feeding duration in Ethiopian women in southern California. PMID- 2213991 TI - Gender differences in health care. PMID- 2213992 TI - Tropical chronic calcific pancreatitis in children. PMID- 2213993 TI - Use of kanwa-cooked cowpea (Vigna unguiculata) in infant food formulation: effect on protein utilization and digestibility. PMID- 2213994 TI - Neurologic aspects of spasmodic dysphonia. AB - We discuss the etiology of 100 spasmodic dysphonia patients. Seventy-one patients had underlying essential tremor, 25 had Meige's syndrome, 12 were hypothyroid, and 27 had either a functional disturbance or focal dystonia. Six patients had intermittent breathy dysphonia. A large corpus of spasmodic dysphonia patients have organic neurolaryngeal disease. PMID- 2213995 TI - Histopathology of vocal cord palsy from recurrent laryngeal nerve damage. AB - The detailed postmortem laryngeal findings of a man with an established vocal cord palsy from an inoperable bronchial carcinoma is presented. Fine dissection of the monoblock specimen from skull base to superior mediastinum allowed sampling of vagus, recurrent and superior laryngeal nerves at different levels for fiber counts in order to compare the affected left and unaffected right side. Horizontal slicing of the whole larynx showed that the main cause of lateral displacement of the paralyzed left cord was gross atrophy of the underlying intrinsic laryngeal muscles. Cricothyroid muscle and superior laryngeal nerves were unaffected. Lateral cord drift due to underlying muscle atrophy is a better explanation of paralyzed cord position in this case than the Wagner and Grossmann theory of cord palsy. PMID- 2213996 TI - Comparison of surgical approaches to the skull base. AB - The surgical accessibility of many complex areas of the base of the skull has expanded rapidly in recent years, as has the literature on these procedures. Several routes to each anatomic region have been described, although little has been written or illustrated comparing and contrasting the different approaches to the skull base. Thirteen representative surgical approaches will be discussed, accompanied by diagrams of accessible anatomic regions. Key features of each procedure will be compared and contrasted. A uniform presentation will be used, showing the incision for each procedure as well as the accessible anatomic areas in three views. Modern imaging techniques permit CT and MR data to be viewed in similar projections, facilitating the choice of surgical procedures. PMID- 2213997 TI - Aberrant carotid artery: recognition on high resolution computed tomography. AB - In the investigation of a pulsatile retrotympanic mass it is important to recognize the high resolution computed tomography findings of an aberrant internal carotid artery. These include an absent exocranial opening of the carotid canal and a tubular density coursing along the medial wall of the middle ear in continuity with the horizontal carotid canal through a dehiscence of the lateral carotid plate. Our report highlights an unusual variation where two anomalous arteries, an aberrant internal carotid and an inferior tympanic to petrous carotid anastomoses, course through the middle ear. PMID- 2213998 TI - Spontaneous otoacoustic emissions: incidence and short-time variability in normal ears. AB - More than 50% of normal ears generate spontaneous otoacoustic emissions, which are sinusoidal tones originating in the cochlea. These faint sounds with levels typically at 10 dB to -30 dB are usually not recognized by the subjects who have them, but can be recorded by sensitive microphones in the ear canal. The clinical significance of having or not having spontaneous emissions are at present unknown. The emissions may be useful for non-invasive monitoring of cochlear physiology. A total of 307 spontaneous otoacoustic emissions from 59 ears have been examined. The short-time variability was small when as many as 300 averages were collected. High-frequency emissions showed better stability than low frequency ones. The ratio of frequency distance between neighboring emissions to critical bandwidth (Bark) was preferentially 0.3-0.5 for lower frequencies and 0.2-0.4 for the higher ones. Amplitude dependence for one emission on its neighbors was difficult to demonstrate. Combination tones (different tones f2-f1 and the cubic distortion product 2 x f1-f2) are probably rare among spontaneous emissions. PMID- 2213999 TI - The perilymphatic fistula: the end of an enigma? AB - While the existence of a perilymphatic fistula may be suggested on the basis of a patient's history and physical findings, at present the diagnosis can only be established by the identification of the actual fistula at the time of tympanotomy. In some cases, repeated reaccumulation of clear colorless fluid within the middle ear is interpreted as representing perilymph and has been considered to indicate the presence of a fistula that cannot be visualized. This subjective type of observation is made by the operating surgeon and is consequently subject to bias. At the present time there is no objective method, such as histopathology, to confirm the diagnosis of a perilymphatic fistula in this type of situation. As a result, there is some variation and controversy in the otology literature as to what surgical findings at tympanotomy should be considered as "proof" of a perilymphatic fistula. In this paper we will propose a new method for confirmation of the diagnosis of perilymphatic fistulas based on a unique biochemical property of perilymph. PMID- 2214000 TI - Self-induced vertigo. AB - Benign paroxysmal positional vertigo is the most commonly recognized form of self induced vertigo. This paper describes other means by which patients have been able to induce vertigo to the extent that at times it has been incapacitating. Hypotheses for the production of these phenomena are suggested in a number of the cases. Some of the features cannot be explained on the basis of our present knowledge of the vestibular system. PMID- 2214001 TI - Cervicofacial liposuction: results and controversies. AB - Obtaining ideal results with cervicofacial rhytidectomy has long frustrated facial plastic surgeons due to the difficulty of removing local excesses of adipose tissue in the parotid, melolabial, submental and submandibular areas. Open and closed liposuction techniques are being developed in conjunction with the facelift to improve definition of the facial, mandibular and cervical contours. A review of the senior author's (PAA) cases of cervicofacial liposuction and rhytidectomy is presented with emphasis placed on surgical techniques and results. Current literature is reviewed. Recommendations are made regarding analysis, surgical techniques and postoperative management of patients presenting for rejuvenation of the lower face. PMID- 2214002 TI - Septorhinoplasty in children: benefits of the external approach. AB - Following a series of septorhinoplasties performed on 28 children over a period of eight years as well as a review of the literature, the authors consider that the taboo on this sort of surgery would seem to have passed. Given that the septum plays a fundamental role in the projection of the nasomaxilliary complex, it is clear that certain surgical rules must be applied: the perichondrium must be left intact, no wide cartilaginous resections must be made, the areas of contact between the septum, the vomer, and the perpendicular lamina of the ethmoid must be reconstituted, and finally, the remodeled cartilage must be repositioned. For all of the above reasons, the external approach, performed on 20 children, is the best suited for this sort of operation. No serious long-term complications were observed. PMID- 2214003 TI - Foregut duplication arising from the pharynx. AB - An unusual case of duplication of the foregut arising from the posterior pharyngeal wall is presented. Pertinent embryological and etiological considerations are discussed and a literature review included. PMID- 2214004 TI - Hodgkin's disease in the nasopharynx. AB - Nasal obstruction due to adenoid hypertrophy is extremely common in the pediatric age group and is generally successfully treated by adenoidectomy. The case report of the incidental finding of Hodgkin's disease in an adenoidectomy specimen will be presented. Overall, for all age groups and stages of disease, fewer than 75 cases of Hodgkin's disease with nasopharyngeal involvement have been reported in the world literature. Further, fewer than 15 cases had isolated primary involvement. Although unusual, the occurrence of primary adenoidal Hodgkin's disease in our patient supports the submission of adenoidal tissue for micropathological examination when a relatively large amount of tissue is found at the time of surgery. PMID- 2214005 TI - Recurring giant-cell granuloma at the site of previous radiation therapy. AB - A 15-year-old girl presented with an aggressive giant-cell granuloma (GCG) of the maxilla with local invasiveness and bony destruction. The tumor recurred twice and attained a diameter of 6 cm. Previously, this patient had had two hematologic malignancies for which she had received therapeutic doses of radiation to the site where the GCG occurred. It is therefore possible that this tumor was radiation induced. PMID- 2214006 TI - Cavernous hemangioma of the internal auditory meatus. AB - A case is reported of angiomatous malformation involving the facial and vestibilocochlear nerves within the internal auditory meatus. The relative incidence of tumors and other space-occupying lesions occurring in this area is reviewed, along with the relative advantages of different imaging techniques. PMID- 2214007 TI - The carotid ghost. A color Doppler ultrasound duplication artifact. AB - Color Doppler ultrasound examinations of the neck frequently demonstrate an artifactual region of color assignment deep to the common carotid artery that simulates blood flow in deep cervical arteries. Based on analysis of imaging performed on 10 normal volunteers, it was shown that the pulsed Doppler waveform originating from the artifact was identical to that of the common carotid artery. It was also shown that the artifact was always located deep to the common carotid artery regardless of location and positioning of the transducer. In vitro modeling using a flow phantom confirmed that the appearance was artifactual in nature. The mechanism of production most likely is related to a mirroring phenomenon at the deep wall of the common carotid artery. PMID- 2214008 TI - Sonographically demonstrated intra-amniotic hemorrhage following transplacental genetic amniocentesis. Frequency, sonographic appearance, and clinical significance. AB - Over a 9-month period, 11 transplacental amniocenteses were performed. Following completion of amniocentesis, intra-amniotic hemorrhage occurred in all 11 cases. Amniotic masses and intra-amniotic strands occurred in three cases as a result of intra-amniotic hemorrhage. The 11 pregnancies in which transplacental amniocentesis were performed were uncomplicated, and they resulted in normal infants. Transplacental amniocentesis can yield unusual sonographic appearances but does not appear to have an adverse effect on pregnancy outcome. PMID- 2214009 TI - Detection of rejection in renal allografts. Evaluation with duplex sonography and DTPA renal scintigraphy with kidney/aorta perfusion ratios. AB - Duplex sonography and technetium-99m DTPA renal scintigraphy have been used to distinguish acute rejection from other forms of renal allograft dysfunction. In this study, duplex sonography and renal scintigraphy were compared as methods to detect rejection. Eighty-four episodes of renal allograft dysfunction that had concurrent duplex sonography and renal scintigraphy over a 17-month period were reviewed. During the duplex sonography examinations the resistive index (RI) was measured from the renal cortex. Scintigrams were evaluated for allograft perfusion and function. The kidney to aorta (K/A) ratio was calculated from the upstroke of the perfusion curve. All diagnoses were established by clinical criteria. Histologic proof was available in 49 cases. There were two episodes of hyperacute rejection, 30 episodes of acute rejection, 14 episodes of chronic rejection, and 38 episodes of dysfunction without rejection. Using an RI greater than or equal to 0.70, the sensitivity and specificity for detecting acute rejection were 90% and 76%, respectively, compared with 37% and 76% for renal scintigraphy. The K/A ratio was not helpful in the diagnosis of rejection. PMID- 2214010 TI - Single-needle insertion in twin amniocentesis. AB - Amniocentesis in twin gestation is an uncommon event for most medical centers. The current technique used for this procedure includes two or more needle insertions and the introduction of dye into the first sac. A new approach that consists of a single insertion is proposed. The advantages of this alternate technique are that it requires only one insertion, it is a swifter procedure, it does not require the injection of dye, and it offers positive proof of tapping the two gestational sacs. Although this technique may have some potential risks, in our judgment the advantages outweight the potential risks, and this technique should be considered and its feasibility evaluated in cases of twin gestation requiring two-sac tapping. PMID- 2214011 TI - Use of endo-vaginal ultrasound to optimize visualization of the distal fetal spine in breech presentations. AB - Endovaginal ultrasound was used to evaluate the spine of 13 second-trimester fetuses in which transbdominal images were considered equivocal due to suboptimal visualization of the distal spine and where the fetus was in a breech presentation. Endovaginal sonography demonstrated a small defect in the distal spine and a meningomyelocele in one of the 13 cases. In all of the remaining 12 cases, endovaginal sonography resulted in improved visualization of morphologic detail, providing sufficient information regarding bony anatomy to exclude splaying of the posterior elements. Additionally, in 10 cases the intact skin surface overlying the distal spine, which was not seen by transbdominal sonography, was well demonstrated by endovaginal ultrasound. The authors recommend that endovaginal ultrasound be considered to optimize visualization of the distal fetal spine when transbdominal images are inconclusive and the fetus is in a breech presentation. PMID- 2214012 TI - Three-dimensional spatial registration and interactive display of position and orientation of real-time ultrasound images. AB - Ultrasound images may be difficult to interpret because of the lack of an image orientation display. To resolve this problem, a three-dimensional (3-D) ultrasound scanner has been constructed that provides spatial registration and display of position and orientation of real-time images while allowing unconstrained movement of the scanning transducer. It consists of a conventional sector scanner, a 3-D acoustical spatial locater, and a personal computer. It displays within each image the line of intersection of two image planes, a reference image, and a live image. This display guides and documents image positioning. The scanner's 3-D data also provide the potential for computergraphic modeling of organs, the ability to calculate volumes using nonparallel, nonintersecting image planes, and the capability for 3-D color flow mapping and measurement of Doppler angle. PMID- 2214013 TI - Sonographic appearance of Menetrier's disease in a child. PMID- 2214014 TI - Prenatal ultrasonographic appearance of "agenesis" of the ductus arteriosus and pulmonic valve hypoplasia. A case report and review of the embryogenesis. PMID- 2214015 TI - Disappearing fetal umbilical cord masses. Are these findings suggestive of urachal anomalies? PMID- 2214016 TI - Site-directed mutagenesis of the codon for Ile-25 in gPr80env alters the neurovirulence of ts1, a mutant of Moloney murine leukemia virus TB. AB - ts1, a spontaneous temperature-sensitive mutant of Moloney murine leukemia virus TB, causes hind-limb paralysis in mice. A Val-25----Ile substitution in gPr80env is responsible for temperature sensitivity, inefficient processing of gPr80env, and neurovirulence. In this study, the Ile-25 in gPr80env was replaced with Thr, Ala, Leu, Gly, and Glu by site-directed mutagenesis of the codon for Ile-25 to generate a new set of mutant viruses, i.e., ts1-T, -A, -L, -G, and -E, respectively. The phenotypic characteristics of these mutant viruses differed from those of ts1. For each mutant, the degree of temperature sensitivity was correlated with the degree of inefficient processing of gPr80env, and the following rank order was observed for both parameters: ts1-E greater than ts1-G greater than ts1-L greater than ts1-A greater than ts1 greater than ts1-T. In FVB/N mice, mutant viruses of low and intermediate temperature sensitivity and inefficiency in processing of gPr80env were neurovirulent and consistently caused mutant-specific disease profiles: ts1-T caused severe whole-body tremor, ts1-A generally caused hind-limb paralysis, and ts1-L generally caused a delayed-onset paraparesis. By 150 days postinfection, FVB/N mice that were infected with ts1-G and -E, mutants of high temperature sensitivity and inefficiency in processing of gPr80env, had lymphoid leukemia instead of a neurological disease. These results suggest that the dynamics of gPr80env processing are important in determining the neurovirulent phenotype in vivo. PMID- 2214017 TI - Binding of p53 and p105-RB is not sufficient for oncogenic transformation by a hybrid polyomavirus-simian virus 40 large T antigen. AB - To identify regions on the large T antigens of simian virus 40 (SV40) and polyomavirus which are involved in oncogenic transformation, we constructed plasmids encoding hybrid polyomavirus-SV40 large T antigens. The hybrid T antigens were expressed in G418 sulfate-resistant pools of rat F2408 cells, and extracts of such pools were immunoprecipitated with an antibody against p53. Two hybrid T antigens containing SV40 amino acids 337 to 708 bound to p53, whereas another hybrid T antigen containing SV40 amino acids 412 to 708 did not. This suggests that a binding domain on SV40 large T antigen for p53 is contained within amino acids 337 to 708, with amino acids 337 to 411 playing an important role. One of the two hybrids that bound to p53 was chosen for further study. This T antigen contained SV40 large T antigen amino acids 336 to 708 joined to polyomavirus large T antigen amino acids 1 to 521 (PyT1-521-SVT336-708). Immunoprecipitation with antibodies directed against the product of the retinoblastoma susceptibility gene, p105-RB, showed that this hybrid bound p105 RB as well as p53. Pools expressing the hybrid PyT1-521-SVT336-708 did not grow in soft agar, nor did they form foci on confluent monolayers of nontransformed F2408 cells. The hybrid T antigen was expressed at levels comparable to those seen in retrovirus-infected F2408 cells expressing only SV40 large T antigen, which do show a transformed phenotype. Thus, this level of expression was sufficient for transformation by SV40 large T antigen but not for the hybrid large T antigen. These data, combined with genetic studies from other laboratories, suggest that complex formation with p53 and p105-RB is necessary but not sufficient for the oncogenic potential of papovavirus large T antigens. PMID- 2214018 TI - Construction and use of a human immunodeficiency virus vector for analysis of virus infectivity. AB - We constructed a recombinant human immunodeficiency virus (HIV) vector to facilitate studies of virus infectivity. A drug resistance gene was inserted into a gp160- HIV proviral genome such that it could be packaged into HIV virions. The HIV genome was rendered replication defective by deletion of sequences encoding gp160 and insertion of a gpt gene with a simian virus 40 promoter at the deletion site. Cotransfection of the envelope-deficient genome with a gp160 expression vector resulted in packaging of the defective HIV-gpt genome into infectious virions. The drug resistance gene was transmitted and expressed upon infection of susceptible cells, enabling their selection in mycophenolic acid. This system provides a quantitative measure of HIV infection, since each successful infection event leads to the growth of a drug-resistant colony. The HIV-gpt virus produced was tropic for CD4+ human cells and was blocked by soluble CD4. In the absence of gp160, noninfectious HIV particles were efficiently produced by cells transfected with the HIV-gpt genome. These particles packaged HIV genomic RNA and migrated to the same density as gp160-containing virions in a sucrose gradient. This demonstrates that HIV virion formation is not dependent on the presence of a viral envelope glycoprotein. Expression of a murine leukemia virus amphotropic envelope gene in cells transfected with HIV-gpt resulted in the production of virus capable of infecting both human and murine cells. These results indicate that HIV can incorporate envelope glycoproteins other than gp160 onto particles and that this can lead to altered host range. Like HIV type 1 and vesicular stomatitis virus(HIV) pseudotypes, gp-160+ HIV-gpt did not infect murine NIH 3T3 cells that bear human CD4, confirming that these cells are blocked at an early stage of HIV infection. PMID- 2214019 TI - The P gene product of hepatitis B virus is required as a structural component for genomic RNA encapsidation. AB - Encapsidation of the pregenomic RNA into nucleocapsids is a selective process which depends on specific RNA-protein interactions. The signal involved in the packaging of the hepatitis B virus (HBV) RNA pregenome was recently defined as a short sequence located near the 5' end of that molecule (Junker-Niepmann et al., EMBO J., in press), but it remained an open question which viral proteins are required. Using a genetic approach, we analyzed whether proteins derived from the HBV P gene play an important role in pregenome encapsidation. The results obtained with point mutations, deletions, and insertions scattered throughout the P gene clearly demonstrate that (i) a P gene product containing all functional domains is required both for the encapsidation of HBV pregenomic RNA and for packaging of nonviral RNAs fused to the HBV encapsidation signal, (ii) known enzymatic activities are not involved in the packaging reaction, suggesting that P protein is required as a structural component, and (iii) P protein acts primarily in cis, i.e., pregenomic RNAs from which P protein is synthesized are preferentially encapsidated. PMID- 2214020 TI - Vaccinia virus gene encoding a 30-kilodalton subunit of the viral DNA-dependent RNA polymerase. AB - Antibody was raised against purified vaccinia virus RNA polymerase and used to screen a recombinant vaccinia virus-lambda gt11 library. The DNA from several immunopositive clones was shown by Southern hybridization to originate from the vaccinia virus HindIII E fragment. The nucleotide sequence of the RNA polymerase subunit gene predicts a polypeptide 287 amino acids in length and 30,000 daltons in mass. An early transcript with a 5' terminus just upstream of the putative initiation codon was identified by S1 nuclease protection and primer extension analyses, demonstrating that this RNA polymerase subunit is expressed as an early viral gene product. The RNA polymerase subunit was synthesized by a bacterial expression vector to demonstrate that it corresponds to the previously described 37,000-dalton RNA polymerase subunit. PMID- 2214021 TI - Env and Vpu proteins of human immunodeficiency virus type 1 are produced from multiple bicistronic mRNAs. AB - Three size classes of human immunodeficiency virus type 1 (HIV-1) mRNAs are produced in infected cells: full-length, intermediate, and small. Here we report that the intermediate-size class of viral mRNAs is heterogeneous, consisting of at least 12 differentially spliced species. This group contains nine bicistronic mRNAs producing Env and Vpu and three mRNAs expressing only the first exon of tat. In the latter mRNAs, Env and Vpu expression is blocked by the presence of the upstream tat open reading frame. We conclude that internal initiation of translation is not the mechanism for generation of the bicistronic env mRNAs. Translation of HIV-1 mRNAs is consistent with the scanning mechanism in which Env is produced by leaky scanning from mRNAs that contain env as the second or third reading frame. Env and Vpu proteins are expressed from the same mRNAs and are coordinately regulated by Rev. This arrangement may reflect a requirement for coordinate expression of Vpu and Env. PMID- 2214022 TI - The E2 signal sequence of rubella virus remains part of the capsid protein and confers membrane association in vitro. AB - The capsid (C) protein of rubella virus is translated from a 24S subgenomic mRNA as the first part of a polyprotein containing all three structural proteins of the virus. It is separated from the following protein (E2) by signal peptidase, which cleaves after the E2 signal sequence. We raised an antipeptide antiserum directed against the signal sequence and used the antiserum to show that this sequence is still a part of the C protein in the mature virion. Furthermore, we also showed that, when the C protein is synthesized by in vitro transcription and translation, the resultant protein is membrane associated. This association is not seen with a variant C protein which lacks the signal sequence, and a normally soluble protein (dihydrofolate reductase) becomes membrane associated when the signal sequence is placed at its carboxy terminus. PMID- 2214023 TI - Transcription factors NFI and NFIII/oct-1 function independently, employing different mechanisms to enhance adenovirus DNA replication. AB - Initiation of adenovirus DNA replication is strongly enhanced by two transcription factors, nuclear factor I (NFI) and nuclear factor III (NFIII/oct 1). These proteins bind to two closely spaced recognition sequences in the origin. We produced NFI and NFIII/oct-1, as well as their biologically active, replication-competent DNA-binding domains (NFI-BD and the POU domain), in a vaccinia virus expression system and purified these polypeptides to apparent homogeneity. By DNase I footprinting and gel retardation, we show that the two proteins, as well as their purified DNA-binding domains, bind independently and without cooperative effects to their recognition sequences. By using a reconstituted system consisting of the purified viral proteins (precursor terminal protein-DNA polymerase complex (pTP-pol) and DNA-binding protein, we show that NFIII/oct-1 or the POU domain stimulates DNA replication in the absence of NFI or NFI-BD and vice versa. When added together, the enhancing effect of the two transcription factors was independent and nonsynergistic. Interestingly, stimulation by NFI or NFI-BD was strongly dependent on the concentration of the pTP-pol complex. At low pTP-pol concentrations, NFI or NFI-BD stimulated up to 50 fold, while at high concentrations, the stimulation was less than twofold, indicating that the need for NFI can be overcome by high pTP-pol concentrations. In contrast, stimulation by NFIII/oct-1 or the POU domain was much less dependent on the pTP-pol concentration. These data support a model in which NFI enhances initiation through an interaction with pTP-pol. Glutaraldehyde cross-linking experiments indicate contacts between pTP-pol and NFI but not NFIII/oct-1. The site of interaction is located in the NFI-BD domain. PMID- 2214024 TI - Nucleotide sequence analysis and expression from recombinant vectors demonstrate that the attachment protein G of bovine respiratory syncytial virus is distinct from that of human respiratory syncytial virus. AB - Bovine respiratory syncytial (BRS) virus causes a severe lower respiratory tract disease in calves similar to the disease in children caused by human respiratory syncytial (HRS) virus. While there is antigenic cross-reactivity among the other major viral structural proteins, the major glycoprotein, G, of BRS virus and that of HRS virus are antigenically distinct. The G glycoprotein has been implicated as the attachment protein for HRS virus. We have carried out a molecular comparison of the glycoprotein G of BRS virus with the HRS virus counterparts. cDNA clones corresponding to the BRS virus G glycoprotein mRNA were isolated and analyzed by dideoxynucleotide sequencing. The BRS virus G mRNA contained 838 nucleotides exclusive of poly(A) and had a major open reading frame coding for a polypeptide of 257 amino acid residues. The deduced amino acid sequence of the BRS virus G polypeptide showed only 29 to 30% amino acid identity with the G protein of either the subgroup A or B HRS virus. However, despite this low level of identity, there were strong similarities in the predicted hydropathy profiles of the BRS virus and HRS virus G proteins. A cDNA molecule containing the complete BRS virus G major open reading frame was inserted into the thymidine kinase gene of vaccinia virus by homologous recombination, and a recombinant virus containing the BRS virus G protein gene was isolated. This recombinant virus expressed the BRS virus G protein, as demonstrated by Western immunoblot analysis and immunofluorescence of infected cells. The BRS virus G protein expressed from the recombinant vector was transported to and expressed on the surface of infected cells. Antisera to the BRS virus G protein made by using the recombinant vector to immunize animals recognized the BRS virus attachment protein but not the HRS virus G protein and vice versa, confirming the lack of antigenic cross-reactivity between the BRS and HRS virus attachment proteins. On the basis of the data presented here, we conclude that BRS virus should be classified within the genus Pneumovirus in a group separate from HRS virus and that it is no more closely related to HRS virus subgroup A than it is to HRS virus subgroup B. PMID- 2214025 TI - Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice. AB - Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic demyelinating disease in the central nervous system characterized by persistent viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of antigen-presenting molecules that confer resistance to viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for demyelination, infectious virus, and local virus antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal demyelination, indicating that on a B10 background, resistance is inherited as a dominant trait. Although infectious virus, as measured by viral plaque assay, was cleared inefficiently from the central nervous systems of resistant F1 hybrid progeny mice, we found a direct correlation between local viral antigen production and demyelination. These data are consistent with our hypothesis that the immunological basis for resistance is determined by efficient presentation of the viral antigen to the immune system, resulting in local virus clearance and absence of subsequent demyelination. PMID- 2214026 TI - CD4 is retained in the endoplasmic reticulum by the human immunodeficiency virus type 1 glycoprotein precursor. AB - We analyzed coexpression of the human immunodeficiency virus type 1 glycoprotein precursor, gp160, and its cellular receptor CD4 in HeLa cells to determine whether the two molecules can interact prior to transport to the cell surface. Results of studies employing coprecipitation, analysis of oligosaccharide processing, and immunocytochemistry showed that newly synthesized CD4 and gp160 form a complex prior to transport from the endoplasmic reticulum (ER). CD4 expressed by itself was transported efficiently from the ER to the cell surface, but the complex of CD4 and gp160 was retained in the ER. This retention of CD4 within the ER is probably a consequence of the very inefficient transport of gp160 itself (R. L. Willey, J. S. Bonifacino, B. J. Potts, M. A. Martin, and R. D. Klausner, Proc. Natl. Acad. Sci. USA 85:9580-9584, 1988). Retention of CD4 in the ER by gp160 may partially explain the down regulation of CD4 in human immunodeficiency virus type 1-infected T cells. Inhibition of CD4 transport appears to be a consequence of the interaction of two membrane-bound molecules, because a complex of CD4 and gp120 (the soluble extracellular domain of gp160) was transported rapidly and efficiently from the ER. PMID- 2214027 TI - Heterogeneity and evolution rates of delta virus RNA sequences. AB - To investigate the geographical divergence of delta virus RNA sequences, 868 nucleotides (nt), including the delta antigen-coding region, were determined in isolates from two Japanese patients, M and S, by polymerase chain reaction and direct sequencing and compared with three previously reported nucleotide sequences. The sequence obtained for hepatitis delta virus RNA from patient M was approximately 92% identical to sequences previously obtained for two other strains of hepatitis delta virus, whereas the sequence of hepatitis delta virus RNA obtained from patient S was approximately 81% identical to the previously sequenced strains. This suggests that delta agent in Japan has a heterogeneous origin and the delta virus RNA sequence from Japanese patient S is the most divergent delta virus isolate yet analyzed. To study the evolution rate of delta virus RNA, viral isolates obtained 3 and 4 years apart from each of two patients were also sequenced. It was estimated that the substitution rate of viral RNA was 0.57 x 10(-3) nt per site per year in patient M and 0.64 x 10(-3) nt per site per year in patient S for the delta antigen gene. PMID- 2214028 TI - Moloney murine leukemia virus integration protein produced in yeast binds specifically to viral att sites. AB - The integration protein (IN) of Moloney murine leukemia virus (MuLV), purified after being produced in yeast cells, has been analyzed for its ability to bind its putative viral substrates, the att sites. An electrophoretic mobility shift assay revealed that the Moloney MuLV IN protein binds synthetic oligonucleotides containing att sequences, with specificity towards its cognate (MuLV) sequences. The terminal 13 base pairs, which are identical at both ends of viral DNA, are sufficient for binding if present at the ends of oligonucleotide duplexes in the same orientation as in linear viral DNA. However, only weak binding was observed when the same sequences were positioned within a substrate in a manner simulating att junctions in circular viral DNA with two long terminal repeats. Binding to att sites in oligonucleotides simulating linear viral DNA was dependent on the presence of the highly conserved CA residues preceding the site for 3' processing (an IN-dependent reaction that removes two nucleotides from the 3' ends of linear viral DNA); mutation of CA to TG abolished binding, and a CA to TA change reduced affinity by at least 20-fold. Removal of either the terminal two base pairs from both ends of the oligonucleotide duplex or the terminal two nucleotides from the 3' ends of each strand did not affect binding. The removal of three 3' terminal nucleotides, however, abolished binding, suggesting an essential role for the A residue immediately upstream of the 3' processing site in the binding reaction. These results help define the sequence requirements for att site recognition by IN, explain the conservation of the subterminal CA dinucleotide, and provide a simple assay for sequence-specific IN activity. PMID- 2214029 TI - Analysis of the junctions between human immunodeficiency virus type 1 proviral DNA and human DNA. AB - Integrated retroviral DNA is flanked by short direct repeats of the target DNA. The length of these repeats is specific for the provirus that is integrated (H.E. Varmus, in J.A. Shapiro, ed., Mobile Genetic Elements, 1983). For the human immunodeficiency virus type I (HIV-1), the length of the direct repeats in the target DNA was shown to be 5 bp in one case (Muesing et al., Nature [London] 313:450-458, 1985) and 7 bp in another (Starcich et al., Science 227:538-540, 1985). One possible explanation for this discrepancy is that the direct repeats flanking HIV-1 proviruses are variable. To investigate this, we analyzed the junctions between HIV-1 proviral DNA and human DNA from nine individual clones. In each clone the provirus was flanked by a 5-bp direct repeat of human DNA. Analysis of the proviral clone previously described as being flanked by a 7-bp direct repeat of target DNA (Starcich et al., op. cit.) revealed that this clone was flanked by a 5-bp repeat instead. Therefore, we conclude that HIV-1 proviruses are flanked by 5-bp direct repeats of human DNA. The sequences of the 5-bp duplications from the different proviral clones do not have any apparent similarity to each other or to HIV-1 DNA. PMID- 2214030 TI - Sequence requirements for integration of Moloney murine leukemia virus DNA in vitro. AB - Normal replication of Moloney murine leukemia virus (MoMLV) requires the integration of a DNA copy of the viral RNA genome into a chromosome of the host. In this work, we characterize the DNA sequences at the ends of the linear proviral precursor that are required for integration in the presence of MoMLV integration protein in vitro. We found that nine bases of MoMLV DNA at each end of a linear model substrate were sufficient for near-maximal levels of integration and that four bases of MoMLV DNA at each end were sufficient for low levels of correct integration. We also found that a 3'-terminal A residue was preferred for integration. We infer from the limited DNA sequence requirements for integration that factors in addition to DNA sequence direct integration protein to act at the ends of the viral DNA. PMID- 2214031 TI - Removal of 3'-OH-terminal nucleotides from blunt-ended long terminal repeat termini by the avian retrovirus integration protein. AB - The avian myeloblastosis virus integration protein (IN) was capable of removing a specific set of 3'-OH-terminal nucleotides from blunt-ended long terminal repeat (LTR) substrates which resembled linear viral DNA in vivo. The 3'-OH-recessed ends map to the in vivo site of integration on linear viral DNA. The linear DNA plasmid substrate was formed by the generation of a unique DraI restriction enzyme site (TTT/AAA) at the circle junction of a 330-bp tandem LTR-LTR insert. IN preferentially released the three T nucleotides from the minus strand of the U3 LTR substrate compared with its ability to remove the three T nucleotides from the plus strand of the U5 LTR substrate. It was also observed that IN was capable of cleaving a non-LTR DNA substrate containing sequence homology to the U5 LTR terminus. PMID- 2214032 TI - Determination of influenza virus proteins required for genome replication. AB - An artificial vaccinia virus vector-driven replication system for influenza virus RNA has been developed. In this system, a synthetic NS-like gene is replicated and expressed by influenza virus proteins supplied through infection with vaccinia virus recombinant vectors. The minimum subset of influenza virus proteins needed for specific replication and expression of the viral ribonucleoprotein was found to be the three polymerase proteins (PB1, PB2, and PA) and the nucleoprotein. PMID- 2214033 TI - Oligomeric organization of gp120 on infectious human immunodeficiency virus type 1 particles. AB - The oligomeric structure of the human immunodeficiency virus type 1 envelope glycoprotein (gp120) was examined by treating infectious virions with chemical cross-linking agents and subjecting the protein to sodium dodecyl sulfate polyacrylamide gel electrophoresis and velocity centrifugation. Immunoblots of cross-linked samples revealed three gp120 bands and an approximately threefold shift in gp120 sedimentation. Our finding of cross-linking solely between gp120 suggests that the gp120 subunits are closely associated in the native envelope structure. PMID- 2214034 TI - The importance of routine surveillance of distal bypass grafts with duplex scanning: a study of 379 reversed vein grafts. AB - To assess the utility of routine duplex surveillance, 379 infrainguinal reversed vein grafts performed at two independent teaching hospitals were prospectively entered into a surveillance protocol from March 1986 through August 1989. An average of 3.2 postoperative duplex graft flow velocity (GFV) measurements per graft was obtained during a mean follow-up interval of 21 1/2 months. Only 2.1% of 280 grafts with GFV measurements greater than 45 cm/sec failed within 6 months of a normal surveillance examination. GFV measurements less than 45 cm/sec in 99 grafts led to arteriography in 75 grafts, identifying 50 stenotic lesions in 48 bypasses (12.6% of series). Inflow lesions were present in 5%, outflow stenoses in 2%, and intrinsic graft stenoses in only 6% of bypasses. Only 29% of grafts identified as failing by duplex scan were associated with a reduction in ankle brachial index of greater than 0.15. Secondary reconstructions were performed in 48 grafts based on detection of a reduced GFV measurement; all such reconstructions are patent after a mean follow-up of 5 months. Duplex surveillance is more reliable in identification of failing vein grafts than is determination of ankle-brachial index. PMID- 2214035 TI - Recurrent thoracic outlet syndrome. AB - Recurrent symptoms develop in 15% to 20% of patients undergoing either first rib resection or scalenectomy for thoracic outlet syndrome. Over the past 22 years 134 operations for recurrence were performed in 97 patients. Four operations were used: transaxillary first rib resection (26); supraclavicular first rib resection with neurolysis (15); scalenectomy with neurolysis (58); and brachial plexus neurolysis (35). Complications included temporary plexus injury (0.7%), temporary phrenic palsy (3.7%), and permanent phrenic palsy (1.4%). The combined primary success rate of all four operations for recurrence was 84% in the first 3 months. This fell to 59% at 1 to 2 years; 50% at 3 to 5 years; and 41% at 10 to 15 years. No significant difference was found in results between the four operations used for recurrence. When recurrence was caused by trauma the results of reoperations were better than when recurrence was spontaneous. The primary success rates of three initial operations for thoracic outlet syndrome were compared to their secondary success rates (improved after reoperation). By use of life-table methods, reoperation improved the 5- to 10-year success rate of transaxillary first rib resection from 69% to 86% and for scalenectomy from 69% to 84%. Reoperation is successful in most cases of recurrent thoracic outlet syndrome and better when recurrence is the result of a neck injury. PMID- 2214036 TI - Experimental and early clinical evaluation of vascular anastomoses with argon laser fusion and the use of absorbable guy sutures: a preliminary report. AB - This study investigated the feasibility of forming vascular anastomoses by use of argon laser tissue fusion and absorbable, monofilament polydimethylsiloxane guy sutures. In initial animal studies femoral arteriovenous fistulas approximately 1.5 cm in length were created bilaterally in each of 10 dogs and were studied histologically at 2, 4, 8, 16, and 24 weeks (two animals in each interval). In each animal, one anastomosis (control) was formed with continuous 6-0 polypropylene suture, and the contralateral anastomosis (experimental) was performed with an argon laser (0.5 watt, 5 to 7 minutes exposure, energy fluence 1100 to 1500 joules/cm2 per 1 cm length) with stay sutures of 5-0 polydimethylsiloxane at 0.5 to 0.65 cm intervals. At removal, all anastomoses were patent without hematomas, aneurysms, or luminal narrowing. Histologic examination at 2 to 16 weeks demonstrated resorption of the biodegradable suture material by a local inflammatory reaction. By 24 weeks, laser-fused specimens had no evidence of suture material at the anastomotic line, and healing consisted of a bond between artery and vein wall tissues. Control suture specimens at the same intervals exhibited an organized fibrous tissue response to the suture. Clinical adaptability of this technology has subsequently been evaluated in five patients at 10 to 27 months (21.6 +/- 5.8) by physical examination and duplex scanning and demonstrate no evidence of abnormal healing. This study establishes the experimental and preliminary clinical feasibility of laser-fused anastomoses aligned by biodegradable guy sutures and supports further investigation and refinement of the technique. PMID- 2214037 TI - Extraperitoneal endarterectomy for iliofemoral occlusive disease. AB - Sixty patients with iliofemoral occlusive disease were treated by autogenous anatomic reconstruction by endarterectomy. Endarterectomy was performed extra peritoneally by the eversion technique. The operative technique and its advantages and disadvantages are discussed. Six patients had postoperative complications of acute anastomotic hemorrhage (two patients), would hematoma (two patients), and atelectasis (two patients). Sixty patients discharged with patient arterial reconstruction were followed up from 5 months to 17 1/2 years, with a mean follow-up of 53 months. There were no other vascular complications. Seventy limbs were at risk during this period, with an accumulative patency rate of 80.4% at 5 years and 71.4% at 10 years. There were 11 occlusions of the external iliac artery and one stenosis of the common femoral artery. Failures occurred mainly in the external iliac artery, which appears to be the limiting factor in the continued patency of endarterectomy. There were 18 deaths (30%). Nine deaths were attributed to the complications of arteriosclerosis. PMID- 2214038 TI - The fate of residual saphenous vein after partial removal or ligation. AB - Duplex scanning was used to study residual greater and lesser saphenous vein segments in 14 limbs with previous partial distal greater saphenous vein removal, 19 limbs with partial proximal greater saphenous vein removal, 29 limbs with total greater saphenous vein removal, 10 limbs with high greater saphenous vein ligation, as well as 37 contralateral unoperated and 8 other normal limbs. Partial distal removal showed better preservation of residual greater saphenous vein than partial proximal removal, with greater preservation of "usable" length and greater average diameter. Compared to contralateral unoperated legs, partial distal removal, partial proximal removal, and total removal all showed a similar degree of compensatory lesser saphenous vein enlargement. High ligation showed no lesser saphenous vein enlargement but showed the best greater saphenous vein preservation, none had less than 85% preservation of potential length. Combining residual greater saphenous vein and lesser saphenous vein segments of usable caliber, 100% of high ligation, 93% of partial distal removal, and 74% of partial proximal removal had greater than 60 cm total length, and most total removal had greater than 40 cm usable residual lesser saphenous vein. Previous saphenous vein surgery should not categorically exclude patients as having no usable residual ipsilateral vein for bypass. Partial distal removal allows better preservation of length and caliber of residual greater saphenous vein than proximal harvest, with both showing equivalent lesser saphenous vein enlargement to those with total greater saphenous vein removal. High ligation, performed for early tributary varicosities, in patients with saphenofemoral but no perforator incompetence, gives excellent preservation of residual greater saphenous vein length and caliber. Sclerotherapy to tributary varicosities did not obliterate distal greater saphenous vein segments. PMID- 2214039 TI - The influence of neutralizing heparin after carotid endarterectomy on postoperative stroke and wound hematoma. AB - The influence of neutralizing or not neutralizing heparin after carotid endarterectomy on postoperative stroke and wound hematoma is unknown. During the past 6 years some of the authors frequently gave protamine sulfate to neutralize heparin, whereas others did not unless a patch was used or wound hemostasis was not readily obtained. To determine the influence of protamine sulfate on stroke and wound hematoma the records of 697 patients having a carotid endarterectomy from January 1984 to September 1989 were reviewed. Protamine sulfate was given to 328 patients, and 369 did not receive protamine sulfate. The incidence of stroke in the two groups was 1.8% (n = 6) and 2.7% (n = 10), respectively, and the difference was not significant (p = 0.6019). Excluding three strokes that could not be related to neutralizing or not neutralizing heparin, the difference remained insignificant (1.5% vs 2.2%, p = 0.7290). The incidence of wound hematoma was 1.8% (n = 6) in patients given protamine sulfate and 6.5% (n = 24) in patients not given protamine sulfate, and this difference was significant (p = 0.0044). The difference remained significant when three hematomas not related to protamine sulfate were excluded (1.2% vs 6.2%, p = 0.0013). In patients not given protamine sulfate draining the wound lessened the incidence of wound hematoma (4.4% vs 8.6%), but this difference was not statistically significant (p = 0.1475). In patients given protamine sulfate the dose of protamine sulfate (15 to 45 mg vs 50 to 75 mg) had no statistically significant effect on the incidence of stroke (0.8% vs 2.0%, p = 0.6530) or wound hematoma (1.6% vs 1.0%, p = 1.000). PMID- 2214040 TI - Duplex scanning of normal or minimally diseased carotid arteries: correlation with arteriography and clinical outcome. AB - This study evaluated the role of duplex scanning in the management of patients with normal or minimally diseases carotid arteries. Carotid duplex scans were interpreted according to previously established criteria and considered normal when pulsed Doppler spectral waveforms showed laminar flow or only minor flow disturbances. Normal flow patterns were noted by duplex scanning in 100 carotid bifurcations of 72 patients who also underwent carotid arteriography. Neurologic symptoms (amaurosis fugax, transient ischemic attack, or stroke) were present in relation to 23 arteries and absent in relation to 77 arteries. On the 23 symptomatic sides arteriography was interpreted as normal in eight, 1% to 15% stenosis in 14, and 16% to 40% stenosis in one. For the 77 asymptomatic sides, arteriography showed normal vessels in 15, 1% to 15% stenosis in 43, and 16% to 40% stenosis in 19. One symptomatic patient was treated by carotid endarterectomy for an irregular 1% to 15% stenosis. None of the asymptomatic lesions were in the range of 80% to 99% stenosis, which would justify endarterectomy for asymptomatic disease. Clinical follow-up for a mean interval of 28 months on 20 of the 22 symptomatic patients not undergoing surgery revealed no strokes and transient recurrent symptoms in two patients. Assuming that the single operation in this study was indicated, duplex scanning correctly identified lesions not requiring carotid endarterectomy in 96% (22/23) of the symptomatic patients. A normal duplex scan also predicted a benign clinical outcome without operation. Duplex scanning can reliably exclude surgically treatable carotid bifurcation lesions in asymptomatic patients, and endarterectomy is rarely indicated in symptomatic patients with normal duplex scan results. This study supports a nonoperative therapeutic approach for most patients with neurologic symptoms and a normal carotid duplex scan on the appropriate side. PMID- 2214041 TI - Propagation of deep venous thrombosis identified by duplex ultrasonography. AB - To investigate the efficacy of anticoagulation in preventing continuing thrombosis, we prospectively evaluated 24 patients with acute deep venous thrombosis using duplex ultrasonography. All patients were hospitalized with conclusive ultrasonic evidence of deep venous thrombosis identified in one of four levels: I, calf only; II, calf-popliteal; III, calf-popliteal-femoral; or IV, calf-popliteal-femoral-iliac. Duplex scans were obtained on admission and on three subsequent occasions during therapy. Progression of thrombosis was defined as advancement of thrombus to the more proximal venous level. Demographic data, symptoms, risk factors for deep venous thrombosis, physical findings, anticoagulation regimens, and hematologic variables were ascertained. Adequacy of anticoagulation was defined as elevation of baseline activated partial thromboplastin time by 150%. Nine patients (38%) had progression of thrombosis, and 15 (62%) had stable or improving duplex scans. Progression occurred as follows: I----II (2), I----III (2), II----III (1), and III----IV (4). Of the demographic and clinical variables examined, only smoking correlated with progression of thrombus (p = 0.04). Average heparin dose in the stable group was 1214 +/- 294 units/hr and 1122 +/- 248 units/hr in the group that progressed (p = 0.8): activated partial thromboplastin time was 45.6 +/- 7 seconds in the stable group and 49.8 +/- 9 seconds in the progression group (p = 0.7). Nine patients in the stable group had consistently adequate anticoagulation, whereas six did not; six in the progression group were consistently anticoagulated, and three were not. Two patients (one with stable thrombus and one with progressive thrombus) suffered nonfatal pulmonary emboli. Clot progression as determined by duplex scanning did not predict acute complications of deep venous thrombosis. PMID- 2214042 TI - Re-endothelialization of isolated segments of the canine carotid artery with reference to the possible role of the adventitial vasa vasorum. AB - This study was designed to determine if the adventitial vasa vasorum contribute to re-endothelialization of the canine carotid artery after removal of the endothelial flow surface. Casting studies demonstrated that vasa vasorum are present only in the adventitia of the canine carotid artery. Ninety autograft segments of the carotid artery from which the endothelium had been removed were implanted in both carotid arteries of 45 dogs. Glutaraldehyde-processed canine carotid allografts were positioned at each end to prevent pannus ingrowth and a Gore-Tex wrap to prevent periarterial tissue growth was placed into the outer wall. Three methods were used, with observations at 4 and 8 weeks. In method 1 the test segment was treated with superficial endarterectomy. In method 2 a balloon catheter was used to remove the endothelium. In method 3 balloon catheter denudation of the flow surface was also employed and, in addition, the adventitia was removed surgically as completely as possible, although a few vasa vasorum were shown to remain in some grafts. In method 1 all the patent endarterectomized arteries were partially re-endothelialized at both the 4- and 8-week intervals. In method 2, 72% of the balloon-denuded patent arteries with intact adventitial vasa vasorum were partially re-endothelialized at 4 weeks and 84% at 8 weeks. However, in method 3 the flow surfaces had no endothelium at 4 weeks and 83% still had none at 8 weeks. These findings suggest that, in the absence of pannus ingrowth, re-endothelialization of the canine carotid artery depends on not only the presence but also the number of adventitial vasa vasorum. PMID- 2214043 TI - Clinical spectrum of symptomatic external iliac fibromuscular dysplasia. AB - External iliac fibromuscular dysplasia is a rare and usually asymptomatic disorder. We report eight symptomatic patients seen over a 15-year period and review pathophysiologic mechanisms accounting for the three following distinct lower extremity ischemic sequelae: (1) Emboli--episodic focal digital ischemia (blue toe) was seen in three patients. Resection and primary anastomosis of focal iliac ulcerative fibromuscular dysplasia (one patient) or resection and replacement (two patients) removed the embolic source and relieved the symptoms. (2) Chronic ischemia--gradual onset of full leg claudication in four patients was treated by operative graduated intraluminal dilation in three patients and prosthetic bypass in one. Arteriography subsequently showed a remodeled lumen in the three patients who underwent dilation. (3) Dissection--acute onset leg ischemia resulted from presumed dissection of the external iliac segment. After 4 months of conservative management of antiplatelet agents and exercise, symptoms resolved completely, and arteriogram showed spontaneous restoration of a normal lumen in the dissected segment. The clinical presentation of fibromuscular dysplasia may mimic other arterial processes such as atherosclerosis. Diagnosis is made only by arteriography with specific magnification views of the external iliac arteries and careful surveillance of the renal arteries. Appropriate treatment should be tailored to the clinical presenting symptom. For microembolic disease, resection and replacement are required. For chronic ischemia, intraluminal dilation is generally sufficient and durable and has proved to be a simpler and acceptable alternative to replacement or bypass. In acute dissection, surgical intervention may be deferred if the limb is viable to allow spontaneous healing and remodeling. Persistent symptoms may be the only indication for intervention in this ischemic manifestation of external iliac fibromuscular dysplasia. PMID- 2214044 TI - Thrombus propagation and level of anticoagulation. PMID- 2214045 TI - Initial clinical evaluation of carotid artery laser endarterectomy. AB - Clinical study of carotid artery laser endarterectomy began April 15, 1988. This report describes the first 10 cases that were performed in nine patients (five men and four women, mean age 70 years). Indications were asymptomatic stenosis (5), transient ischemic attacks (4), and stroke in evolution (1). There were two emergency cases and eight elective cases (including one reoperative case). Surgical exposure, systemic heparinization, vascular control, and a longitudinal arteriotomy were used. The cleavage plane between atheromas and media was developed with argon ion laser radiation (488 and 514.5 nm) directed through a 300 microns quartz fiber at power 1.0 W. Laser radiation was used to cut the atheromas out of the arteries and weld the end points. Residual atheromatous debris were vaporized with individual laser exposures. Arteriotomies were closed with sutures, and blood flow was restored. The endarterectomies were 3.9 +/- 1.1 cm long and required 330 +/- 97 joules. Mean clamp time was 22.5 +/- 7.9 minutes. Shunts were used in two cases. There were no arterial perforations or injuries as a result of laser light. Complications were hematoma (1), respiratory arrest (1), and transient neurologic deficit (1). Carotid endarterectomy is technically feasible with argon ion laser radiation. In the present series, postoperative observations, averaging 12 months and ranging from 5 to 19 months, have shown satisfactory results. No angiographic follow-up examinations were carried out. PMID- 2214046 TI - Abdominal aortic aneurysm associated with aortic hypoplasia and polycystic kidneys. PMID- 2214047 TI - Safety of peripheral vascular surgery after recent acute myocardial infarction. PMID- 2214048 TI - Educators say MD-PhD degree programs make sense, but prove it. PMID- 2214049 TI - What goes up must come down, but hypertension experts worldwide differ about ways, means. PMID- 2214050 TI - Secretary of Health, Human Services to hear recommendations for improving immunization. PMID- 2214052 TI - From the Centers for Disease Control. Health benefits of smoking cessation. PMID- 2214051 TI - Cancer Institute takes a look at ascorbic acid. PMID- 2214053 TI - From the Centers for Disease Control. Smoking-related mortality decline among physicians--Rhode Island. PMID- 2214054 TI - From the Centers for Disease Control. Smokers' beliefs about the health benefits of smoking cessation--20 U.S. communities, 1989. PMID- 2214055 TI - The future of health care: military model? Canadian cost cutting. PMID- 2214056 TI - Benefits and harms: the balance sheet. PMID- 2214057 TI - Cytotechnologists' proficiency and laboratory regulations. PMID- 2214058 TI - Government studies of physician-owned laboratories. PMID- 2214059 TI - Informing physicians about promising new treatments for severe disease. PMID- 2214060 TI - Biopsy of occult breast lesions and professional liability. PMID- 2214061 TI - A piece of my mind. Taps. PMID- 2214062 TI - Changes in quality of care for five diseases measured by implicit review, 1981 to 1986. AB - We measured quality of care before and after implementation of the prospective payment system. We developed a structured implicit review form and applied it to a sample of 1366 Medicare patients with congestive heart failure, acute myocardial infarction, pneumonia, cerebrovascular accident, or hip fracture who were hospitalized in 1981-1982 or 1985-1986. Very poor quality of care was associated with increased death rates 30 days after admission (17% with very good care died vs 30% with very poor care). The quality of medical care improved between 1981-1982 and 1985-1986 (from 25% receiving poor or very poor care to 12%), although more patients were judged to have been discharged too soon and in unstable condition (7% vs 4%). Except for discharge planning processes, the quality of hospital care has continued to improve for Medicare patients despite, or because of, the introduction of the prospective payment system with its accompanying professional review organization review. PMID- 2214063 TI - Prospective payment system and impairment at discharge. The 'quicker-and-sicker' story revisited. AB - Since the introduction of the prospective payment system (PPS), anecdotal evidence has accumulated that patients are leaving the hospital "quicker and sicker." We developed valid measures of discharge impairment and measured these levels in a nationally representative sample of patients with one of five conditions prior to and following the PPS implementation. Instability at discharge (important clinical problems usually first occurring prior to discharge) predicted the likelihood of postdischarge deaths. At 90 days postdischarge, 16% of patients discharged unstable were dead vs 10% of patients discharged stable. After the PPS introduction, instability increased primarily among patients discharged home. Prior to the PPS, 10% of patients discharged home were unstable; after the PPS was implemented, 15% were discharged unstable, a 43% relative change. Efforts to monitor the effect of this increase in discharge instability on health should be implemented. PMID- 2214064 TI - From the Office of the General Counsel. Economic considerations in treatment decisions and the standard of care in medical malpractice litigation. PMID- 2214065 TI - Meet Kimberly Bergalis--the patient in the 'dental AIDS case'. PMID- 2214066 TI - Ultrasonic catheters give cardiologists boost in observing internal blood vessels. PMID- 2214067 TI - AMA Science Reporters' Conference explores wide range of clinical problems, approaches. PMID- 2214068 TI - From the Centers for Disease Control. Healthy people 2000: national health promotion, disease prevention objectives for the year 2000. PMID- 2214069 TI - The effects of polyunsaturated fat vs monounsaturated fat on plasma lipoproteins: the power of a study. PMID- 2214070 TI - Hip surgery and venous thrombosis: effect of anesthesia. PMID- 2214071 TI - Mother's milk turns toxic following fish feast. PMID- 2214072 TI - The effect of lay advertising on breast-feeding prevalence. PMID- 2214073 TI - Hope hype hit. PMID- 2214074 TI - Truth is stranger than fiction department: the surgeon, the radiologist, the authors, and JAMA got it right. PMID- 2214075 TI - Transcervical balloon tuboplasty. A multicenter study. AB - Transcervical balloon tuboplasty represents a noninvasive technique to treat proximal tubal occlusion. In a multicenter study, 77 women with confirmed bilateral proximal tubal occlusion underwent the procedure. In 71 patients (92%), at least one proximally obstructed fallopian tube was recanalized. Concomitant distal bilateral tubal occlusions were diagnosed after successful proximal tubal balloon recanalizations in 13 patients (17%). In the remaining 64 patients, 22 clinical pregnancies (34%) have been confirmed during a median follow-up period of 12 months. Among those, 17 (77%) resulted in normal deliveries and five (23%) resulted in a first-trimester miscarriage. One patient was diagnosed with an ectopic pregnancy. Among 25 patients who had not conceived within 6 months of the procedure, 17 (68%) demonstrated continuing tubal patency on repeated hysterosalpingogram. We conclude that transcervical balloon tuboplasty is a safe outpatient technique that may represent an alternative to in vitro fertilization or microsurgical reanastomosis of fallopian tubes. PMID- 2214076 TI - Transmission of HIV-1 infections from mothers to infants in Haiti. Impact on childhood mortality and malnutrition. The CDS/JHU AIDS Project Team. AB - Of 4588 pregnant women in a high-risk Haitian population, 443 (9.7%) were serologically positive for the human immunodeficiency virus type 1 (HIV-1). Infants born to women who were HIV-1 seropositive were more likely to be premature, of low birth weight, and malnourished at 3 and 6 months of age than were infants born to women who were HIV-1 seronegative. Increased mortality was observed in infants born to women who were HIV-1 seropositive by 3 months of age. At 12 months of age, 23.4% of the infants born to women who were HIV-1 seropositive had died compared with 10.8% of the infants born to women who were HIV-1 seronegative; at 24 months of age, the mortality rates were 31.3% and 14.2%, respectively. Maternal HIV-1 infections resulted in an 11.7% increase in the overall infant mortality rate in this population. The estimated mother-to infant HIV-1 transmission rate in these breast-fed infants was 25%, similar to the rates reported for non-breast-fed populations in the United States and Europe. PMID- 2214077 TI - Acute sensorineural deafness in Lassa fever. AB - A prospective audiometric evaluation of 69 hospitalized febrile patients in Sierra Leone, West Africa, revealed a sensorineural hearing deficit (SNHD) in 14 (29%) of 49 confirmed cases of Lassa fever and in 0 of 20 febrile controls. An SNHD was present in nine (17.6%) of 51 people who had evidence of previous Lassa virus infection. Twenty-six of 32 local residents who had previously sustained a sudden deafness had antibody titers to Lassa virus of 16 or greater, compared with six of 32 matched controls. Lassa fever is associated with an incidence of SNHD, which considerably exceeds that previously reported with any other postnatally acquired infection, and accounts for a prevalence of virus-related hearing impairment in the eastern province of Sierra Leone that is greater than that reported from anywhere else in the world. PMID- 2214078 TI - Apartheid medicine. Health and human rights in South Africa. AB - Human rights and health care under apartheid in South Africa were studied. Human rights violations, such as detention without charge or trial, assault and torture in police custody, and restriction orders, have had devastating effects on the health of persons experiencing them. These violations have occurred in the context of a deliberate policy of discriminatory health care favoring the white minority over the black majority. South Africa's medical societies have had mixed responses to the health problems raised by human rights violations and inequities in the health care system. The amelioration of health care for all and prevention of human rights violations depend on ending apartheid and discrimination and greater government attention to these problems. PMID- 2214079 TI - Does age affect outcomes of out-of-hospital cardiopulmonary resuscitation? AB - We examined the relation between age and outcomes in patients treated for out-of hospital cardiac arrest in Seattle, Wash. Considering all out-of-hospital cardiac arrests treated by paramedics over a recent 5-year period, 386 (27%) of 1405 consecutive patients aged 70 years or older were resuscitated and admitted to a hospital vs 474 (29%) of 1624 younger patients; 140 elderly patients (10%) were discharged alive vs 223 younger patients (14%). Of the 140 elderly patients, 112 went home and 28 went to a nursing home. Considering only patients whose initial rhythms were ventricular fibrillation, the percent of patients discharged alive was substantially higher: 120 (24%) of 493 for elderly patients and 194 (30%) of 639 for younger patients. Elderly patients can benefit from attempted resuscitation from out-of-hospital cardiac arrest. PMID- 2214080 TI - Can employers exclude women to protect children? PMID- 2214081 TI - Life-sustaining therapies in elderly persons. PMID- 2214082 TI - Deafness associated with Lassa fever. PMID- 2214083 TI - A piece of my mind. Consoling Mrs Byrne. PMID- 2214084 TI - Late-night admissions: resident education and sleep patterns. PMID- 2214085 TI - Diagnostic and therapeutic technology assessment. Alpha-interferon and chronic myelogenous leukemia. PMID- 2214086 TI - Preoperative evaluation of young woman with an acute abdomen. PMID- 2214087 TI - John H. Talbott, MD: 10th JAMA editor. PMID- 2214088 TI - New allergy society, formed to advocate in vitro laboratory test, wins reimbursement victory. PMID- 2214089 TI - Nobel prizes emphasize clinical applications. PMID- 2214090 TI - From the National Institutes of Health. PMID- 2214091 TI - From the Centers for Disease Control. Progress toward achieving the 1990 high blood pressure objectives. PMID- 2214092 TI - Home births and minimal medical interventions. PMID- 2214093 TI - Latchkey children and guns at home. PMID- 2214094 TI - Homicide rates and firearm availability. PMID- 2214095 TI - Measles vaccination. PMID- 2214096 TI - Points of potential IQ lost from lead. PMID- 2214097 TI - Lead poisoning from the use of Indian folk medicines. PMID- 2214098 TI - 'Old man in a VA hospital': shock and dismay. PMID- 2214099 TI - Effects of Medicaid eligibility expansion on prenatal care and pregnancy outcome in Tennessee. AB - To investigate the effects of a 1985 Tennessee Medicaid regulatory change that expanded eligibility coverage specifically for married women during pregnancy, we studied vital statistics files linked to Medicaid enrollment files. The greatest Medicaid coverage increase in terms of an absolute difference in rates and the number of women covered occurred in white married women younger than 25 years with less than 12 years of education, where enrollment increased 18%. However, in that group of mothers, as well as for the total of all mothers studied, there were no concomitant improvements in use of early prenatal care, birth weight, or neonatal mortality. Analysis of the timing of enrollment relative to the beginning of pregnancy showed that more than two thirds of the women who enrolled did so after the first trimester. PMID- 2214100 TI - Intrapleural tetracycline for the prevention of recurrent spontaneous pneumothorax. Results of a Department of Veterans Affairs cooperative study. AB - This prospective, multicenter, randomized, "unblinded," controlled clinical trial was designed to determine if the intrapleural instillation of 1500 mg of tetracycline hydrochloride would be effective in diminishing the ipsilateral rate of recurrence for spontaneous pneumothorax. During the 4-year enrollment period, 113 patients were assigned to the tetracycline group; 116 patients were assigned to the control group. During the 5-year study period, the recurrence rate in the tetracycline group (25%) was significantly less than that in the control group (41%). Use of tetracycline seemed to reduce the recurrence rates for patients with either primary or secondary spontaneous pneumothorax and for patients with either an initial or a recurrent pneumothorax. We conclude that the intrapleural administration of tetracycline in patients with spontaneous pneumothorax significantly reduces the rate of ipsilateral recurrence but is associated with intense chest pain. Intrapleural tetracycline therapy is indicated for patients with a spontaneous pneumothorax who are hospitalized and are treated with tube thoracostomy. PMID- 2214101 TI - Caffeine and ventricular arrhythmias. An electrophysiological approach. AB - Little information is known regarding caffeine's effect on the substrate supporting sustained ventricular arrhythmias. This prospective study evaluated the effect of coffee (275 mg of caffeine) on this substrate with programmed ventricular stimulation in 22 patients with a history of symptomatic nonsustained ventricular tachycardia, ventricular tachycardia, or ventricular fibrillation. Patients underwent electrophysiological testing before and 1 hour after coffee ingestion. Mean (+/- SEM) plasma caffeine level achieved after coffee consumption was 6.2 +/- 0.5 mg/L. Mean plasma catecholamine and potassium values were not altered significantly 1 hour following caffeine ingestion. The number of extrastimuli required to induce an arrhythmia was unchanged in 10 patients (46%), increased in six (27%), and decreased in six (27%). Rhythm severity was unchanged in 17 patients (77%), more severe in two (9%), and less severe in three (14%). In those patients with clinical ventricular arrhythmias, caffeine did not significantly alter inducibility or severity of arrhythmias, suggesting little effect on the substrate supporting ventricular arrhythmias. PMID- 2214102 TI - Life and death in the US Army. In Corpore sano. AB - Using standardized mortality ratios, this study compares the sex- and race specific, age-adjusted death rates for all US Army soldiers with those for the entire US population. Results show that soldiers are currently dying at a rate that is only half that of their civilian counterparts. The most striking difference in death rates by cause is a markedly lower homicide death rate for Army black men; homicides among the civilian black male population are 12 times more frequent than in the Army. Some factors that might account for these lower mortality rates in the Army are discussed. PMID- 2214103 TI - Epidemiologic, clinical, and laboratory findings of human ehrlichiosis in the United States, 1988. AB - In 1988, the Centers for Disease Control and the Oklahoma State Department of Health identified 40 patients who had a fourfold or greater change in antibody titer in response to Ehrlichia canis. The median age of these patients was 42 years, 83% were male, 76% became ill between May and July, and 92% reported recent exposures to ticks. Patients resided in or were exposed to ticks in 14 states, including five where ehrlichiosis had not been reported before 1988. Thirty-four patients (85%) were hospitalized, and many had serious complications, including acute respiratory failure (seven patients), encephalopathy (six patients), and acute renal failure (four patients). Pulmonary infiltrates were demonstrated in 14 patients, cerebrospinal fluid pleocytosis was seen in 10 patients, and elevated levels of serum creatinine were demonstrated in eight patients. Two patients, both of whom had preexisting medical problems, died. Nonhospitalized patients received tetracycline therapy earlier in the course of their illness than hospitalized patients. There was no significant difference in the interval from initiation of antibiotic therapy to the first day of defervescence between patients treated with tetracyclines and those treated with chloramphenicol. PMID- 2214104 TI - Military medicine from World War II to Vietnam. PMID- 2214105 TI - Caring for the wounded in wartime. PMID- 2214106 TI - Medicaid and prenatal care. Necessary but not sufficient. PMID- 2214107 TI - Owl of wisdom. PMID- 2214108 TI - Nonotologic otalgia. PMID- 2214109 TI - Prophylaxis of steroid-induced purpura. PMID- 2214110 TI - Innovation in medical curricula: before and beyond 'new pathways'. PMID- 2214111 TI - Medical education: a symbolic ritual? PMID- 2214112 TI - The Hippocratic oath: a basis for modern ethical standards. PMID- 2214113 TI - Dequantifying the boards. PMID- 2214114 TI - Medicine and magic. PMID- 2214115 TI - [Cardiovascular effects of apnea test in the diagnosis of brain death]. AB - Cardiovascular effects of apnea test were investigated in 12 patients suspected of brain death. Arterial blood gas and cardiovascular hemodynamics were measured just before and after 10-minute apnea. Apnea test induced respiratory acidosis without hypoxemia. Cardiac index increased by 34% (2.3 to 3.1 l.min-1.m-2; P less than 0.01) and systemic vascular resistance index decreased by 30% (3608 to 2519 dynes.sec.cm-5.m-2; P less than 0.01), whereas heart rate and mean arterial pressure were unchanged. Significant increases in mean pulmonary arterial pressure (17.6 to 29.1 mmHg; P less than 0.01), pulmonary vascular resistance index (381 to 616 dynes.sec.cm-5.m-2; P less than 0.01) and right ventricular stroke work index (4.0 to 10.5 g.m.m-2; P less than 0.01) suggest that apnea test increases right ventricular afterload. PMID- 2214116 TI - [Skin blood flow measured by laser Doppler flowmetry under enflurane anesthesia or modified neuroleptanesthesia during abdominal surgery]. AB - In 18 patients for abdominal operations, the skin blood flow of the sole was measured with a laser Doppler flowmeter under general anesthesia. The deep body temperature was also measured. During the induction of anesthesia with thiopental, an elevation of the skin blood flow was observed. The elevation was due to administration of thiopental. After the induction, the elevation appeared to be more prolonged under nitrous-oxide and enflurane anesthesia than under diazepam or droperidol, with nitrous-oxide and fentanyl anesthesia. The persistent elevation was observed for 104 +/- 10 minutes under enflurane anesthesia in 10 patients, but the elevation was 71 +/- 7 minutes under modified neuroleptanesthesia in 8 patients. This difference might be associated with the peripheral vasodilatation by enflurane and the short peripheral vasodilatation by droperidol or diazepam. Increases of the skin blood flow correlated well with the changes of the deep temperature of the sole. These results indicate that the peripheral skin blood flow is different during long operation between enflurane anesthesia and modified neuroleptanesthesia and the laser Doppler flowmetry is a useful tool as a monitor of peripheral circulation and body temperature. PMID- 2214117 TI - [The effects of a small dose of atropine upon sinus bradycardia during spinal anesthesia]. AB - Positive or negative chronotropic effects of atropine and their magnitude are known to be determined by its dose given, concomitant sympathetic tone, and patient's age. Thus, the aim of the present study is to investigate the small effective dose of atropine for acceleration of heart rate in sedated bradycardic patients under spinal anesthesia, and to evaluate the relationship between the heart rate response to atropine and level of analgesia or patient's age. Significant increases in heart rate were observed in patients receiving intravenous atropine 4 micrograms.kg-1 (n = 21) or 6 micrograms.kg-1 (n = 35) except 2 micrograms.kg-1 (n = 18). However, there were wide variations in cardiac responses to atropine among patients in each group. Negative chronotropic responses to atropine were elicited in 10 (56%), 2 (9%), and 1 (3%) of the patients receiving 2 micrograms.kg-1, 4 micrograms.kg-1 and 6 micrograms.kg-1, respectively. Although there was no correlation between the heart rate response to each dose of atropine and the level of spinal anesthesia, the magnitude of positive chronotropic response to atropine of 6 micrograms.kg-1 related inversely with age. The present results suggest that atropine above 4 micrograms.kg-1 is required to accelerate the heart rate in most bradycardic patients under spinal anesthesia irrespective of the level of analgesia. However, it seems appropriate to administer atropine intravenously in a cumulative fashion, because of individual's variability including age in the chronotropic response to atropine. PMID- 2214118 TI - [Platelet catecholamine changes in patients with pheochromocytoma]. AB - In patients with adrenal tumor, the importance of platelet catecholamine was examined. In patients with pheochromocytoma, not only preoperative catecholamine concentrations in blood and urine but also platelet catecholamine content were abnormally high as compared to patients with other adrenal tumors (pheochromocytoma for NE 3383 and E 311, no pheochromocytoma for NE 235 and E 24 pg.mg-1 protein). In the patient with pheochromocytoma, plasma catecholamine concentration showed its peak during the manipulation of the tumor during operation, and it decreased rapidly and returned to normal level the day after operation. On the other hand, platelet catecholamine content showed its peak after operation and returned to normal range on the 7th postoperative day. These results suggest that determination of platelet catecholamine content is useful for pre-operative diagnosis of pheochromocytoma, and that catecholamine in platelet modulates sudden fluctuation in plasma catecholamine concentration. PMID- 2214119 TI - [Changes in platelets and blood coagulation during prolonged ECLA with a heparin bonded hollow fiber membrane lung]. AB - Effects of the heparin bonded artificial membrane lung and circuit on blood coagulation were investigated during prolonged extracorporeal lung assist on goats. A veno-venous bypass ECLA was performed on 18 goats up to 10 days. Twelve of them (Group I) were with a heparin bonded device and the other six (Group II) were with the usual device. In Group I, heparin was continuously infused at a rate of 15.2 units.kg-1.hr-1 to maintain the activated coagulation time, ACT, at around 130 sec., while in Group II, 25.5 units.kg-1.hr-1 of heparin was necessary to maintain ACT at about 200 sec. to prevent blood coagulation in the bypass circuit. Platelets decreased significantly in Group I (by 50% of pre ECLA value) as well as in Group II, but aggregation activity in Group I was higher than in Group II. Fibrinopeptide A and antithrombin III showed no significant difference between the two groups. Autopsy showed no significant pathological findings. ECLA, with a heparin bonded surface, showed excellent blood compatibility and required only a little systemic administration of heparin. The heparin bonded bypass circuit will enable safer ECLA even in patients with some bleeding sites. PMID- 2214120 TI - [Marked changes in the core temperature during anaphylactic shock]. AB - Three cases of anaphylactic shock were reported in which the core temperature was measured continuously. Two core temperature thermister probes were fixed on the forehead and the sole. Temperature dissociation between the core and the periphery disappeared in a few minutes after the administration of the causative agents. The clinical signs of the anaphylactic shock such as erythema, wheal and marked hypotension also developed in a few minutes after the disappearance of temperature dissociation. Thus treatment of anaphylactic shock could be started even before the patients develop severe hypotension. This clinical study suggests that a sudden disappearance of the temperature dissociation is a incipient sign of anaphylactic shock and to monitor the core as well as the peripheral temperature is a useful method for early diagnosis and treatment of anaphylactic shock. PMID- 2214121 TI - [Endocrine and hemodynamic responses to total body hyperthermia in humans]. AB - We investigated effects of total body hyperthermia (TBH) on endocrine and hemodynamic responses. A total of five treatments were performed in five patients with gastric cancer under neuroleptanesthesia with morphine followed by 0.2 to 0.4% enflurane. TBH was extracorporeally induced with veno-venous shunt incorporating with heat exchanger to keep their temperature between 41.5 degrees C and 42.0 degrees C for three hours. The patients were administered angiotensin to maintain tumor blood flow. Lactated Ringer's solution was administered at the rate of 10 to 15 ml.kg-1.hr-1 for five hours. Plasma cortisol levels decreased significantly to about one third of the control value after heating and the levels recovered to the control value after cooling. Plasma norepinephrine level increased significantly to about 7 to 9 times the control value following TBH, but this hormonal response was insufficient to reveal marked direct hemodynamic effects. The magnitude of fall in SVR was more significant in spite of the administration of angiotensin. Cardiac index increased significantly to about 2.0 to 2.6 fold of control value, but mean arterial blood pressure (MAP) decreased significantly to about two thirds to four fifths of the control value. Morphine relieved the hormonal response in ACTH and cortisol strongly, but morphine suppressed hemodynamics by decreasing SVR. Neither norepinephrine released from sympathetic nerve endings nor even 50 to 200 ng.kg-1.min-1 of angiotensin administered failed to restore SVR or MAP during hyperthermia. PMID- 2214122 TI - [Investigation of 121 cases of spinal anesthesia with plain 0.5% bupivacaine]. AB - Bupivacaine has been used for spinal anesthesia since 1982 in our department. We performed a retrograde investigation of 121 cases who had lower limb surgery and anesthetized with plain 0.5% bupivacaine solution during the year of 1987. Doses of bupivacaine, maximum spread of analgesia and spinal tap level were analyzed. We chose the bupivacaine doses from 2.5 ml to 4.0 ml depending on the condition of the patient and the specificity of the surgery. The patients were divided into 3 groups by the dose of bupivacaine: i.e. 3.0, 3.5, 4.0 ml of plain 0.5% bupivacaine. Seventy percent of all patients had a spinal tap on L3/4 interspace. The average upper level of analgesia was T7 in each group and no patient had analgesia above T2 level. There was no correlation between the site of injection and volume of local anesthetics. However patient's physical status and surgical procedure are more important to obtain the good analgesic level. There was no significant respiratory depression nor hypotension during and after the surgery. It is concluded that 3-4 ml of 0.5% bupivacaine provided satisfactory spinal anesthesia for the lower limb surgery. PMID- 2214123 TI - [The effects of thiamylal, ketamine and nicardipine on the hippocampal theta waves produced by cerebral ischemia in cats]. AB - Spontaneous hippocampal electroencephalogram (EEG) was recorded in the pyramidal cell layer (PCL) and dentate gyrus (DG) during and after ischemia produced by bilateral clamping of the common carotid arteries in cats. Hippocampal theta waves, approximately 180 degree out of phase in PCL and DG, appeared within 4.3 +/- 2.3 seconds after the onset of bilateral carotid artery occlusion and continued for more than 60 minute. These hippocampal theta waves disappeared 34.2 +/- 10.2 seconds after 4 vessel occlusion. We could not find the clear difference between the two areas in the appearance and disappearance of the hippocampal theta waves. We further investigated the effects of thiamylal, ketamine and nicardipine on the hippocampal theta waves during bilateral carotid artery occlusion. Thiamylal changed the two hippocampal theta waves to a similar pattern of EEG, which has irregular slow and fast waves, in both PCL and DG. Ketamine changed the two theta waves to irregular complex pattern of fast and slow waves and spike activity, which is independent at two areas. Nicardipine, a Ca antagonist, changed the theta waves to irregular slow waves which were similar to the pattern of EEG observed before carotid artery occlusion. These results indicate that thiamylal, ketamine and nicardipine have different effects on the ischemia of hippocampus. PMID- 2214124 TI - [A comparison of oral- and intramuscular-preoperative administration of ranitidine in children]. AB - The effect of preoperative oral and intramuscular ranitidine administration on intragastric pH and volume was evaluated in children. Thirty healthy inpatients whose ages were 2-13 years, were randomly assigned to three groups. Twelve hours before the elective operation apple juice was given to the control group, and apple juice with 0.4 mg.kg-1 ranitidine to the second group (Oral group). For the third group (IM group) an intramuscular injection of 0.1 mg.kg-1 ranitidine was done. Intragastric pH was significantly elevated and gastric volume was also significantly reduced in IM group, and serum ranitidine concentration showed a high level of 359.4 +/- 85.6 ng.dl-1 (mean +/- SD). In oral group ranitidine effect on pH and volume was not significant, and the drug serum concentration was 31.6 +/- 13.3 ng.dl-1 which was slightly lower than the effective level. Though the intramuscular injection guaranteed safer gastric content, a painful injection is stressful for children. With the knowledge of elimination rate of serum ranitidine we recommend oral ranitidine (0.4 mg.kg-1) six hours preoperatively for pediatric premedication. PMID- 2214125 TI - [Changes in arterial oxygen tension during and after enflurane or halothane anesthesia as well as epidural analgesia]. AB - Recovery from inhalation anesthesia is often marked by the occurrence of postoperative hypoxemia. In this study, we compared the effects of enflurane or halothane anesthesia and epidural analgesia on arterial oxygen tension during and after the operation in 60 ASA physical status 1-2 patients who underwent cholecystectomy. Anesthesia was induced with thiopental and maintained with 66% N2O and -enflurane (1.5%), -halothane (1%), or -epidural lidocaine (1% solution, 17.5 ml) in oxygen. Blood gas analysis was done before and 10, 30, 60 min after induction. PaO2 was measured on 1st and 3rd postoperative days in all patients breathing air spontaneously. PaO2 decreased during operation in all three groups of anesthesia. PaO2 values on first postoperative day were significantly lower than those before operation, and PaO2 value in enflurane group (PaO2 = 67 +/- 1 mmHg) was significantly lower than that in halothane group (PaO2 = 72 +/- 2 mmHg, P less than 0.05). PMID- 2214126 TI - [Liquid crystal thermography; a reliable method for detecting soda lime exhaustion]. AB - The dynamic and functional state of soda lime can be more precisely assessed by measuring changes in wall temperatures of the absorption chambers rather than observing color change of the soda lime granules. We demonstrated in this report that the liquid crystal thermometer is an inexpensive and reliable measuring device for this purpose. PMID- 2214127 TI - [Anesthetic management of a patient with progressive spinal muscular atrophy]. AB - Various problems especially weakness of respiratory muscle and abnormal reaction to muscle relaxant exist during the management of anesthesia for the patients with neuromuscular disease with the disturbance of motor neurons. We had a patient for trans-urethral resection of prostate with spinal progressive muscular atrophy. Using nitrous oxide-oxygen with halothane, and without muscle relaxant, we succeeded in avoiding respiratory failure, aspiration and other serious complications. By measuring serum sodium, rapid discovery and treatment of water intoxication could be achieved. PMID- 2214128 TI - [A case of spinal anesthesia in a 104-year-old woman]. AB - We gave spinal anesthesia for a super-aged patient (104 year-old female) who underwent insertion of prosthesis for femoral neck fracture. One point eight ml of 0.3% dibucaine was used as local anesthetic, and the analgesic below Th10 level was obtained. To monitor the respiratory and circulatory functions during operation, pulse-oximeter and invasive arterial pressure were used. Dopamine and metaraminol were given to prevent hypotension and the operation was completed uneventfully. This anesthetic experience suggests that, for the anesthesia of a super-aged patient it is mandatory not only to clearly identify the complications and the physical features of the patient but also to explain to the patient the anesthetic as well as operative procedures. Besides, we have to manage elderly patients receiving spinal anesthesia carefully, considering intraoperative problems as well as the possibility of resorting to general anesthesia. PMID- 2214129 TI - [Determination of spinal or epidural anesthetic level in patients who cannot communicate well--finger or magnifying glass]. AB - Difficulty to determine level of spinal or epidural anesthesia troubles us in the patients who can not communicate well, for example in patients with hearing loss, depressed CNS with or without depressants and in slowly replying patients with various reasons. We know that one can determine spinal or epidural anesthetic level with stroking the skin with finger with which we can detect different touch sensation, feeling as anesthetized smooth and unanesthetized rough. We thought that different touch sensation is due to perspiration at unblocked skin area. If cause of difference of touch sensation was due to perspiration at unanesthetized area as we thought, perspiration may be visible on unblocked area. We found no perspiration but texture change on the anesthetized skin. We photographed the texture of the blocked skin, before and after spinal anesthesia. The skin texture after the block became shallow and widened. These texture changes give us different touch sensation, rough and scratched before and smooth after the block. We can easily differentiate the blocked from the unblocked skin area with finger or by magnifying glass by which the skin texture change is visible. PMID- 2214130 TI - [37th meeting of the Japanese Society of Anesthesiology. Nagano City, 10-12 May 1990. Abstracts]. PMID- 2214131 TI - Increased cardiovascular responses to norepinephrine in patients with hypertrophic cardiomyopathy. AB - Sympathetic nerve-adrenergic receptor systems have been implicated in the pathogenesis of hypertrophic cardiomyopathy (HCM). We studied plasma norepinephrine (NE) levels during exercise and cardiovascular responses to NE in 26 patients with nonobstructive HCM and 26 age- and sex-matched controls. There were no differences in the plasma NE levels at rest (201 +/- 84 vs 233 +/- 100 pg/ml) or in the slope of the log NE-heart rate relationship during exercise between the HCM patient and control groups. When NE was infused intravenously, with increasing doses to 0.20 microgram/kg/min, HCM patients displayed significantly greater increases in mean blood pressure (29 +/- 7 vs 14 +/- 5%, p less than 0.001) and peripheral vascular resistance (39 +/- 7 vs 26 +/- 7%, p less than 0.001) than controls. Although the fractional shortening decreased during NE infusion in controls, it was unaffected in HCM patients, despite a greater elevation of systolic pressure. The responses of left ventricular contractility, estimated by a ratio of systolic blood pressure to end-systolic dimension, were significantly greater in patients with HCM (31 +/- 7 vs 13 +/- 6%, p less than 0.001). These observations indicate that vasoconstrictive responses of the peripheral arteries and inotropic responses of the left ventricular muscle to NE were augmented in patients with HCM, while sympathetic nervous activity remained unchanged. Accordingly, we propose that increased activity of the cardiovascular adrenergic receptor systems, rather than enhanced sympathetic nervous function, may be related to the development of abnormal hypertrophy in HCM. PMID- 2214132 TI - Effects of a low, oral dose of nisoldipine on the systemic and coronary hemodynamics and the prostaglandin metabolism of ischemic heart disease patients. AB - This study investigated the effects of a low dose of nisoldipine (5 mg, p.o.) in 10 patients with ischemic heart disease. The patients were subjected to a 90-min exercise regimen before and after a 5 mg dose of nisoldipine, using a supine bicycle ergometer adjusted to each patient's limitations. The mean blood plasma level of nisoldipine was 3.8 +/- 3.1 (SD) ng/ml. The drug significantly decreased the systolic arterial pressure in patients throughout the experimental session, whereas a change in the diastolic arterial pressure appeared only at the submaximal stage of the exercise. Additionally, at maximal exercise, nisoldipine caused a decrease in the mean coronary sinus pressure from 11.4 +/- 7 mmHg to 6.5 +/- 5 mmHg (p less than 0.01). By contrast, while at rest, nisoldipine decreased the coronary vascular resistance from 1.5 +/- 0.7 mmHg/ml/min to 1.0 +/- 0.7 mmHg/ml/min (p less than 0.05). After exercise, the drug decreased thromboxane B2 levels from 1133 +/- 907 pg/ml to 720 +/- 379 pg/ml (p less than 0.05) in the coronary sinus blood, and increased the 6 keto-prostaglandin F1 alpha levels from 465 +/- 135 pg/ml to 559 +/- 167 pg/ml (p less than 0.05) in brachial artery blood. This suggests that a low, oral dose of nisoldipine can moderately improve the systemic and coronary hemodynamics and afterloads, and may assist in improving the prostaglandin metabolism in ischemic heart disease patients. PMID- 2214133 TI - The effects of pacing-induced left bundle branch block on left ventricular systolic and diastolic performances. AB - To assess the effects of pacing-induced left bundle branch block on left ventricular (LV) systolic and diastolic performance, we performed digital subtraction ventriculography while simultaneously measuring LV pressure with a catheter tip micromanometer. The subjects included 10 patients with a sinus rhythm, a normal QRS duration and PR interval within 0.22 sec. LV performance was assessed during both right atrial pacing (AP) and atrioventricular sequential pacing (AVP) at the same pacing rate. The atrioventricular pacing interval during AVP was adjusted to be the maximal interval that showed the QRS configuration seen during complete right ventricular pacing. LV end-diastolic pressure and volume during AVP did not differ from those during AP. Peak positive and negative dp/dt during AVP were significantly lower than those during AP. Time constants were also significantly longer during AVP. The QRS duration during AVP significantly correlated with end-systolic volume and time constants, and inversely correlated with ejection fraction and +dp/dt. These observations indicated that conduction disturbance per se, induced by AVP, could not only impair LV systolic performance but also diastolic performance, possibly due to asynchronous contraction and relaxation of the left ventricle. PMID- 2214134 TI - Significance of left atrial pressure and left ventricular relaxation as determinants of left ventricular early diastolic filling flow in man. AB - We analyzed the relationships among parameters of left ventricular (LV) early diastolic filling flow (EDF) obtained with pulsed Doppler echocardiography, mean pulmonary wedge pressure (PCWP) and the time constant of LV pressure fall calculated by either Weiss' (Tw) or Thompson's (Tb) method. PCWP correlated with the peak velocity (R) (r = 0.537, p less than 0.05), acceleration (Ac) (r = 0.545, p less than 0.05) and deceleration (Dc) (r = 0.606, p less than 0.01) of LVEDF. In contrast, Tb correlated only with the time to the peak of LVEDF (TPF) (r = 0.487, p less than 0.05), and Tw did not correlate with the Doppler-derived indices significantly. After correcting for the effect of PCWP, significant partial correlations between R and Tw (r = -0.535, p less than 0.05), and between Ac and both Tw (r = -0.606, p less than 0.01) and Tb (r = -0.569, p less than 0.05) were found. Dc did not correlate with Tw or Tb. These results suggest that the level of left atrial pressure may mask the relationship between parameters of LVEDF and LV relaxation, and that the relations among these variables vary with individual indices of LVEDF. PMID- 2214135 TI - Right ventricular endomyocardial fibrosis. Diagnosis and management. AB - The clinical course, noninvasive and invasive diagnostic findings in 4 patients (pt) with endomyocardial fibrosis are reported. All patients (16-50 years) were in functional class III-IV (NYHA). Central venous pressure with large a- and v waves was elevated in all; liver enlargement and peripheral edema were also noticed in all pts, and ascites in 3. An apical 2/6 systolic murmur was present in 2, and a right parasternal pansystolic murmur 2-4/6 with positive Carvallo's sign in all pts. ECG was non-specific and chest x ray showed right atrial enlargement in every case. A right-sided diastolic plateau which was higher than left ventricular end-diastolic pressure was present in all pts. Echo-, angiocardiography and computed tomography of the heart revealed obliteration of the right ventricular cavity, predominantly localized at the apex. Two pts who underwent endocardial resection and tricuspid valve replacement are alive and well after 9 and 8 years, respectively. One pt died early in the postoperative period and one died waiting for surgical therapy. In conclusion, echo-, angiocardiography and computed tomographic findings are diagnostic. A satisfactory differentiation from other cardiac disorders with restrictive hemodynamics and right-sided heart failure is possible. PMID- 2214136 TI - Energetics of the time-varying elastance model, a visco-elastic model, matches Mommaerts' unifying concept of the Fenn effect of muscle. AB - It is generally believed that the Fenn effect contradicts all visco-elastic models of muscle, including the new elastic body and the time-varying elastance models. Although it is clear that the new elastic body model can be discarded, the Fenn effect does not preclude the time-varying elastance model. Although no visco-elastic models can simulate the extra energy utilization for work above the level of the energy utilized for the maximal isometric contraction, the extra energy observed by Fenn is not generally observed, even in skeletal muscles. However, work-related extra energy utilization, above the isometric energy utilization at equivalent force (Mommaerts' unifying concept of the Fenn effect), is generally observed in both skeletal and cardiac muscles. This unifying concept of the Fenn effect in cardiac muscle can be simulated by a simple time-varying elastance model. This study demonstrates the essential difference in energetics between the new elastic body model and the time-varying elastance model. PMID- 2214137 TI - Adenosine exacerbates ischemic myocardial injury during regional coronary hypoxemia in the dog. AB - To investigate the myocardial protective effect of adenosine (ADO), the left anterior descending artery of 10 dogs was cannulated and perfused at a pressure of 100 mmHg. Hypoxic coronary perfusion was conducted for 60 min followed by 60 min of normoxic reperfusion (group 1, control, n = 5). In group 2 (n = 5), ADO was continuously infused at a rate of 40 micrograms/kg/min for 30 min before and during 60 min of hypoxic blood perfusion and for 60 min following normoxic reperfusion. In group 1, R wave amplitude and TQ segment of the epicardial surface electrocardiogram (EPIECG) were reduced, the ST segment was elevated, and a new Q wave developed during hypoxic blood perfusion. However, at 60 min of normoxic reperfusion, the R wave amplitude recovered to approximately 60% of its control value. Also, ST segment elevation was restored to normal and the new Q wave disappeared. The TQ segment returned to normal after approximately 20 min of hypoxic perfusion. Histological analysis showed myocardial infarction in the subendocardium, but not in the subepicardium. In group 2, EPIECG findings during hypoxic blood perfusion were similar to those observed in group 1. However, the recovery of ST segment elevation during normoxic reperfusion was slower than that observed in group 1. R wave restoration did not occur in group 2. Furthermore, the new Q wave remained present throughout the normoxic reperfusion period. Transmural infarction and severe congestion were observed histologically in this group. Obvious contraction bands were not demonstrated histologically in either group. These findings suggest that ADO did not protect myocardial viability during 60 min of hypoxic blood perfusion, but instead, ADO exacerbated ischemic injury during regional hypoxic perfusion. PMID- 2214138 TI - Structural and functional alterations of mesenteric vascular beds in spontaneously hypertensive rats. AB - The morphology and reactivity of mesenteric arteries from spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY) were investigated. Isolated, perfused mesenteric vascular beds were prepared from 6-, 11- and 18-week-old SHR and WKY. At these ages, the walls and media of large mesenteric arteries were significantly thicker in SHR than in WKY. The number of smooth muscle cell layers in the media was significantly larger in SHR than in WKY. This difference between SHR and WKY increased as rats grew older, in parallel with differences in the blood pressure. Flow rate-perfusion pressure curves indicated that the vascular basal resistance to flow increased more profoundly in SHR preparations than in WKY preparations as rats grew older. This may be related to the structural alterations of the resistance vessel wall in SHR. The pressor responses to KCl were greater in SHR preparations than in WKY preparations as rats grew older. This may be caused partly by the increase of the number of smooth muscle cell layers in the media of SHR resistance vessels. The pressor response to norepinephrine (NE) was significantly higher in SHR preparations than in WKY preparations at all ages investigated. In marked contrast to the vascular basal resistance and the pressor response to KCl, the pressor response to NE was extremely exaggerated in SHR at the age of 6 weeks. This extremely high NE response in younger SHR may not be caused by the structural alteration in resistance vessels. It may be caused by a functional change, which is regulated by the signal transduction process in smooth muscle cells of resistance vessels. These results suggest that the development of hypertension in SHR may be caused by genetic structural and functional abnormalities of resistance vessels. Both abnormalities may be caused by the hyperreactivity to NE through an altered signal transduction process in smooth muscle cells of resistance vessels in SHR. PMID- 2214139 TI - Hypertrophic peripheral neuropathy (Dejerine-Sottas disease) associated with heart block. Case report presentation and review of the literature. AB - We present a case of a male suffering from hypertrophic peripheral neuropathy (Dejerine-Sottas disease) and severe involvement of the cardiac conductive tissue causing syncopal attacks. It is the first time that an association of this neuromuscular disease with cardiac involvement is described. PMID- 2214140 TI - A case of pure thrombus in a saphenous vein graft six years after bypass surgery. AB - A man showed a 90% narrowing at the origin of a saphenous vein graft (SVG) 6 years after bypass surgery. After 4 days of intravenous thrombolytic therapy the narrowing in the SVG disappeared completely. Thus, late stenosis of SVG can be caused by thrombosis not superimposed on organic narrowing. PMID- 2214141 TI - Arrhythmogenic right ventricular dysplasia with sick sinus syndrome and atrioventricular conduction disturbance. AB - Although arrhythmogenic right ventricular dysplasia (ARVD) is believed to involve primarily the right ventricle, left ventricular abnormalities have also been described. We report a case of ARVD with abnormalities of the sinus node, right atrium and atrioventricular node. The biopsies taken from the right atrium and the right ventricle showed replacement of myocardium by fibrous tissue. The pathologic changes of this disease process may extend into the atrium and atrioventricular node. PMID- 2214142 TI - [Epidemiology of malignant tumors of the female genital organs]. AB - Incidence, risk factors, prognosis and 5-year survival of the malignant tumors in the female genital organs, except the trophoblastic diseases, were described. The uterine cervical cancer is the most in Japan, but is already one the controlling cancer, though prognosis of the cervical adenocarcinoma is still poor. Incidence of the endometrial cancer is increasing. Ovarian malignant tumor is one of silent diseases and their 5-year survival rate is very low. Significant of the annual population screening against them was emphasized. PMID- 2214143 TI - [Pathological aspects of gynecological malignancies--early stage cancers and borderline lesions]. AB - Pathology of gynecological malignancies including cancers of the uterus and ovary were described with a particular focus on early stage cancers and borderline lesions. Histological criteria appeared in this paper are mentioned in accordance with The General Rules for Clinical and Pathological Management of Uterine Cervical Cancer and Uterine Body Cancer and WHO Classification of Ovarian Tumours. Carcinogenesis of the uterine and ovarian cancers were also discussed. PMID- 2214144 TI - [Degrees of malignancy and biological behavior in gynecologic cancer]. AB - Recently there has been a rebirth of interest in the grading of gynecologic cancers. The grading of malignant tumors was proposed initially to help clinicians to plan reasonable and effective therapy. Various schemata have been offered to differentiate degrees of malignancy. The grading system of malignant tumors should be simple and reproducible, and it should also be related to the biological behavior of tumors and prognosis. The importance of the grading in endometrial and ovarian cancers has been well accepted. Grading of cervical cancer seems to be of little value. PMID- 2214145 TI - [Histological and clinical classification of gynecological tumours]. AB - Clinical classification of gynecological tumours according to UICC and FIGO, and their histological classification according to WHO and the Japanese general rules for clinical and pathological management of gynecological tumours are presented. We have discussed the following histological topics which have close correlation with the clinical staging of gynecological tumours. 1. Postoperative recording of definite diagnosis according to pTNM and FIGO. 2. Difference of diagnostic criteria between squamous cell and adenocarcinoma of Ia stage of cervical cancer. 3. Differential diagnosis of atypical endometrial hyperplasia and carcinoma in situ in endometrial cancer. 4. Objective findings for corporeal cavity and myometrial invasion of corpus carcinoma. 5. Correlation between histological classification of ovarian tumours and their malignant potentials. 6. Clinical significance of histological diagnosis of ovarian tumours invasion and cytological diagnosis of ascitic fluids. PMID- 2214146 TI - [Diagnostic endoscopy for malignant uterine tumors]. AB - A hysteroscope is a useful tool for detecting uterine tumors developed in the cervical canal and uterine cavity which are invisible areas. The hysteroscopy discloses easily the findings, location, size and extent of the lesions. Consequently more correct biopsies may be obtained than the conventional curettages which are blind procedures. This paper comprises the instrumentation, technique and hysteroscopic findings of the malignant uterine tumors. Observation of the cervical canal, namely cervicoscopy reveals mainly the appearance of normal cervical wall, preinvasive and invasive squamous cell carcinoma, adenocarcinoma and sarcoma. Hysteroscopy reveals the appearance of normal uterine cavity, endometrial carcinoma, sarcoma, metastatic uterine carcinoma, invasive carcinoma infiltrated from the adjacent organs and trophoblastic tumors. As a result, endoscopic features of each uterine malignant tumor are summarized as useful criteria for differential diagnosis. PMID- 2214147 TI - [Diagnostic cytology and histology in the gynecologic malignant tumors]. AB - This report is on the exfoliative cytologic criteria in the diagnoses of uterine cervical, endometrial and ovarian cancer. It is of special importance to establish a differential diagnosis between ectocervical and endometrial lesions when considering adenocarcinomas. Cytological evaluation of ovarian cancers were performed on stump smears from excised surfaces. It is of great importance to pay special attention to the techniques used when obtaining cytologic specimens for evaluation. PMID- 2214148 TI - [Diagnosis: tumor marker]. AB - We have reviewed the clinical usefulness of tumor markers in gynecologic malignancy. In cervical squamous cell carcinoma. SCC and CEA showed increase in frequency of elevated cases according to the clinical stages (FIGO), and the frequency was significantly higher in recurrent cases than in patients with no evidence of disease. In endometrial carcinoma, presently, no specific tumor marker has been found. The diagnostic efficiency of CA 125, CA 19-9 and TPA were 25.2, 23.8 and 32.6, respectively. Further investigation must be necessary to establish markers sensitive enough. In primary ovarian malignancy, combination assay might be much more useful than single assay. The most effective combinations were TPA/CA 125/Ferritin in serous cystadenocarcinoma, and CEA/CA 19 9/TPA in mucinous cystadenocarcinoma. In the monitoring of the disease, it seems to be essential to select suitable combination of markers in each case. In addition, recently, multivariate analysis systems, such as CAMPAS (computer-aided multivariate and pattern analysis system), have become available. PMID- 2214149 TI - [Screening for gynecologic cancer]. AB - Results of mass screening for cervical cancer, endometrial cancer and breast cancer in Miyagi Prefecture were presented. Systems of screening for endometrial cancer and breast cancer are now arranging in Japan. PMID- 2214150 TI - [Surgical treatment of cancer of the uterine cervix]. AB - As a standard therapy on cervical cancer in Japan, Surgical treatment is applied for stage 0-IIb and radiotherapy is applied for stage III and IV at present. In surgical treatment, the adequate surgical method is selected according to the extent of cancer in individual case in order to preserve the function. PMID- 2214151 TI - [Radical radiotherapy of cervical cancer]. AB - At present, surgery and radiotherapy have been employed successfully to manage carcinoma of the cervix. Generally, the choice of treatment is determined primarily by the stage of the disease. Radiotherapy for cervical cancer must be consist ed of external radiotherapy and brachytherapy. Brachytherapy is a significant and important part of the overall management of the patients with cervical cancer. The selection of a given therapeutic modality depends on the general condition of the patients, gross characteristics of the tumor and availability of expertise to offer adequate radiation therapy. PMID- 2214152 TI - [Chemotherapy of cancer of the cervix]. AB - Systemic chemotherapy has been widely used for the purpose of inducing remission of advanced cancer of the cervix. Almost all anti-cancer drugs have been applied to this way of chemotherapy, however, the high effectiveness of cisplatin is worthy of notice, and this drug plays a central role in combination chemotherapy. Local hyperthermia, drug-induced hypertension and intra-arterial infusion of anti cancer drugs are the representative methods to reinforce the effect of chemotherapy. Adjuvant chemotherapy has to be designed to adapt the extremely slow growing potential of residual microcarcinomas after surgery. Oral administration of tegafur for two years is a choice of maintenance chemotherapy preventive against postoperative recurrence. PMID- 2214153 TI - [Surgical treatment of endometrial cancer]. AB - The main treatment of endometrial cancer is surgery. Total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) is the principal surgery for stage I disease. Recently, pelvic lymph node dissection and para-aortic node biopsy is also being performed. For stage II, many surgeons in Japan prefer to do radical hysterectomy, however, its validity is questioned. For stages III and IV, surgery, radiation, chemotherapy and/or hormone therapy are combined, however, TAH and BSO should be performed at least. In 1988, FIGO changed the endometrial cancer staging system from clinical to surgical. According to this new staging, laparotomy should be done first and treatment plans made depending on the result of surgical finding. PMID- 2214154 TI - [Radiation therapy in carcinoma of the endometrium]. AB - A retrospective analysis of 146 patients with carcinoma of the endometrium was carried out. Several kinds of intracavitary irradiation methods has been changed during the past 28 years, the most favorable results was obtained by means of RALS packing method. Five year survival was 100% in stage I, 27.3% in stage II, 18.2% in stage III and 21.5% in total patients treated with radiation therapy alone (33 patients) as compared to those patients who received postoperative irradiation (109 patients) where the survival was 91.4% in stage I, 76.6% in stage II, 71.5% in stage III and 79.8% in total, respectively. Complications of treatment were seen in 9% and 4.5% with radiation alone and postoperative therapy. From these results, an adequate dose distribution by intracavitary irradiation was emphasized for the improvement of local tumor control. PMID- 2214155 TI - [Chemotherapy and endocrine therapy of endometrial carcinoma]. AB - The main treatment of recurrent and advanced endometrial carcinoma are chemotherapy and/or endocrine therapy. Some of the combination chemotherapy, including Cis-platinum are useful in advanced and recurrent endometrial carcinoma, and progestational agents are available for adjuvant chemo-endocrine therapy after operation of endometrial carcinoma. Authors consider the literatures of the chemotherapy and endocrine therapy for endometrial carcinoma and describe our own cases. PMID- 2214156 TI - [Surgical treatment of ovarian cancer]. AB - Stage I a cancer among early ovarian cancers should be classified because of revision of FIGO classification in 1987, therefore preservation of fertility has become expected to date. Furthermore, a maximal debulking surgery as an initial operation, compared to a staging laparotomy, has yielded favorable results in the clinical outcome of advanced ovarian cancers in recent years. Surgical treatment will still make a major role in the future as one of the multiple therapeutic modalities in this disease, although a complete cure can not be obtained by only surgical treatment. PMID- 2214157 TI - [Significance of second look surgery in the therapy of ovarian cancer]. AB - Second look surgery (SLO) has two kinds of significance in therapy of ovarian cancer. One is a diagnostic value in persistence or not of ovarian cancer. The other is a second cytoreductive surgery. SLO as a diagnostic value is very much valuable to determine prognosis and therapies. On the other hand, SLO as a second cytoreductive surgery prolonged survival periods, however did not affect long term survival rate. Hence, their significance of SLO is not established to acquired good prognosis in long term. PMID- 2214158 TI - [Chemotherapy of advanced ovarian cancer]. AB - Cisplatin containing chemotherapy has provoked an epic making revolution in the treatment of advanced ovarian cancer. However, the impact to the long-term survival is still discouraging. In this article, standard regime for first line chemotherapy, dose, administration method, routes, number of cycles and the second line chemotherapy which is the most embraced problem are described. Strategy for the treatment of advanced ovarian cancer would be continued until the development of new drugs which are effective comparable with cisplatin and have no cross resistance with cisplatin. In order to get significant improvement of 5 year survival, complete response by chemotherapy or complete resection by operation or by both is indispensable and partial response is not sufficient. PMID- 2214159 TI - [A plan and a view for better prognosis]. AB - Better prognosis of treatment depends on both the development of activity of early detection and the progress of treatment. There are two important factors for effective detection of endometrial cancer, one is the spread of endometrial cytology and another is the mobilization of examinee in high age. As to the treatment, many clinics are challenging extension of radical hysterectomy such as para-aortic nodes dissection. To avoid the irradiation on the medical stuffs, remote controlled local treatment system will be improved. The appearance of more effective anti-cancer agent is desired. The conditions of an adequate treatment have to realize not only better cure rate, but also healthy after-life. PMID- 2214160 TI - [Treatment and overview for the improvement of prognosis in ovarian cancer]. AB - The current treatment for ovarian cancer introduced the improvement of survival rate by the chemotherapy based on cisplatin and maximum debulking surgery. The prognosis of ovarian cancer is affected by various kinds of factor as age, ps, stage, histology, histological grading and the volume of residual tumor. By our analysis it was shown whether tumor diameter is less than 2 cm or not was critical point. On the other hand, dose intensity of cisplatin is also important. We could show the improvement of survival rate of advanced cases by the treatment of maximum debulking surgery and high intensity of cisplatin. PMID- 2214161 TI - [Bone marrow transplantation as a treatment of accidental total-body irradiation; a review of past experiences]. PMID- 2214162 TI - [Analysis of anti-platelet antibody]. AB - Results obtained by analysis of anti-platelet antibody using flow cytometry (FCM) were as follows. The use of nest gating is useful in analysis of anti-platelet antibody and frequency of antibody production were 32.7% in patients with hematological disorders using FCM method. This method was much correlated to AHG LCT method. The rate of coincidence was 92.1%. And effective rate of platelet transfusion of cross match carried out only by FCM method was 81.3%. Concentration of globulin fraction in patient's serum and avidin-biotin assay are useful for increasing the sensitivity of detection of anti-platelet antibody. Elimination of HLA (Class 1) antigen from platelet's surface is effective in both chloroquine and acid treatment. Background of fluorescent intensity was tendency to low by the acid treatment than by chloroquine one. It is possible that high titer serum of allogeneic anti-platelet specific antibody is able to be identified by means of its fluorescent intensity. PMID- 2214163 TI - [Leukemic immunophenotyping with flow cytometry]. AB - We have evaluated the clinical efficacy and problematic items of flow cytometric surface and intracellular immunophenotyping of leukemic cells. The multi parametric analysis on the results of leukemic phenotyping displayed a possibility of an independent phenotypical classification, but concurrently we recognized complementary relationships between the morphological and phenotypic approaches. Defective information on the morphology of leukemic cells unexpectedly introduced an insufficient quality in performance of leukemic phenotyping. On the other hand, the interpretations of phenotypic outcomes were complicated in cases with mixed leukemia and partial expression of a marker. Finally we hope further integration of the expression spectrum of markers, including the improvement of CD nomenclature system. PMID- 2214164 TI - [Analysis of DNA aneuploidy as a tumor marker]. AB - DNA aneuploidy (DA) was examined in adult leukemia using flow cytometry, and the method and the clinical implication of DA as a tumor marker were evaluated. The method was simple, rapid, objective, quantitative and further did not need any mitotic cells, so was proved to be very useful for screening of DA. While, DA was detected in 50 (27%) out of 185 adult cases with various types of leukemia. The frequencies of DA in the subtypes of leukemia were 55% in ATL, 26% in ALL, 17% in ANLL, 26% in CML-BC and 6% in CLL, respectively. When compared with other subtypes, the frequency in ATL was significantly higher (p less than 0.01), which suggested a special entity of this disease. In general, however, the frequency of DA in leukemia was rather low, which indicated the difficulty in application of DA by itself in diagnosis of leukemia. While, in cases with DA, DA was very useful as a tumor marker in monitoring the clinical course, for example, in the detection of early relapse or recruitment of leukemic cells. Furthermore, DA was found to be a good prognostic factor which indicates a poor prognosis in cases with ANLL and CML-BC. PMID- 2214165 TI - [Anti-coagulant therapy--antithrombin III]. AB - Biological properties and the efficacy of AT III concentrate for the treatment of thromboembolic disorders were evaluated in the patients with AT III deficiency. Commercially available AT III concentrates showed heterogeneity on agarose gel isoelectric focusing, however, they inhibited thrombin in the same manner. At III concentrates were infused to 11 patients with congenital AT III deficiency (4 with thrombosis). Pharmacokinetic parameters of infused AT III were calculated as follows; half time 61.1 +/- 23.0 hr. (58.4 +/- 22.6 hr. in the cases with thrombosis), max increase rate 1.01 +/- 0.3%/U/kg and recovery rate 95.4 +/- 33.3%. Simulation curves adjusted to the multiple administration were correlated well with the actually determined values in the patients and steady state concentration of AT III was achieved by the administration of this concentrate in 12 or 24 hour intervals. Clinically, substitution with AT III concentrate was proved to be effective for the treatment of thromboembolism in these patients. 16 patients with disseminated intravascular coagulation were treated with heparin (6,000 U/day) followed by AT III concentrate (1,500 U/day) administration. Clinical symptoms and laboratory findings were improved in 11 patients. From these results substitution with AT III concentrate was suggested to be beneficial for the prevention or the treatment of thromboembolic disorders in the patients with AT III deficiency. PMID- 2214166 TI - [Treatment of disseminated intravascular coagulation]. AB - Early diagnosis and immediate treatment of the disease responsible for DIC are most important for successful therapy of DIC. Furthermore, it is also necessary to use anticoagulant agents in most cases of DIC. The agents may be classified on the basis of their mode of anticoagulant action into three groups: ones with antithrombin effect, ones with anti-Xa effect or ones with both effect, and each agent is hoped to be chosen appropriately for development of DIC in near future. At present, such anticoagulant agents as standard heparin, antithrombin-III concentrate, gabexate mesilate, nafamostat mesilate, MD-805, low molecular weight heparin, heparan sulfate, activated protein C, are known as drugs for DIC, and each of them was effective for improvement from DIC in our experience. Antifibrinolytic agents, which have been considered to be contraindicated for therapy of DIC, may be good indication for selected cases of DIC with enhanced fibrinolysis such cases as acute promyelocytic leukemia. Antiplatelet agents may be available for some cases of chronic DIC. PMID- 2214167 TI - [Quality control of ISI/INR system in oral anticoagulant therapy]. AB - Ten controlled plasmas and 4 thromboplastin reagents were distributed to 75 laboratories for measurement of prothrombin time (PT). The results were converted to prothrombin activity (PA). prothrombin ratio (PR) and international normalized ratio (INR). Among the 4 different ways of expression, the discrepancy between the results obtained by the different reagents was the smallest when the results were expressed by INR. However, the discrepancy of the results was still remained because of the different assay methods used routinely at these laboratories, even with the use of ISI/NR system (Instrumentation effects). In this study, reference curve of prothrombin time: INR was created using INR reference plasmas, which were selected from commercial control plasma using a standard thromboplastin reagent. INR's of 108 patients' plasmas were calculated by ISI/INR system on one hand, and by the use of the reference curve of the prothrombin: INR on the other hand. It was found that the discrepancy of the results obtained by different assay methods was significantly improved by the latter method, compared to those obtained by the conventional ISI/INR system. PMID- 2214168 TI - [Beneficial characteristics of protease inhibitor as an anticoagulant for extracorporeal circulation]. AB - Clinical characteristics of protease inhibitor, nafamostat mesilate (FUT 175:FUT), as an anticoagulant for extracorporeal circulation (ECC) were evaluated in hemodialysis and membrane plasmapheresis. FUT inhibited broad enzymatic systems including coagulation, platelet, complement, fibrinolysis and kinin cascades, which were commonly activated in the course of ECC. FUT showed regional anticoagulability, in which anticoagulating effects were firmly limited in extracorporeal circuit, and hemostatic time after ECC was significantly shortened by the use of FUT. FUT had no effects on lipid and bone metabolisms and FUT could not be adsorbed to anion exchange resin. These results indicate that FUT possesses superior characteristics as an anticoagulant for ECC to heparin, and FUT is very useful especially for ECC of patients with high bleeding risk. PMID- 2214169 TI - [Effects of anti-platelet agents on shear-induced platelet aggregation]. PMID- 2214170 TI - [Clinical and cytogenetic features in childhood acute lymphoblastic leukemia with 1; 19 translocation]. AB - We studied the clinical and cytogenetic features of 14 acute lymphoblastic leukemia (ALL) patients with 1; 19 translocation. Ten patients had poor prognostic factors such as age over 10 years, hyperleukocytosis over 5 X 10(4)/microliters or high serum lactic dehydrogenase levels over 5,000 IU/l. Two patients had relapsed within 12 months after the onset, but their 5-year survival rate was 84.6%. Cytogenetically, 6 of 14 patients had multiple subclones. Two had the clones with hyperdiploidy greater than 50 chromosomes, which was known to be one of the favorable prognostic factors in childhood ALL. These findings show ALL children with 1; 19 translocation have a more favorable outcome in spite of some high-risk features than hitherto been thought. PMID- 2214171 TI - [Electron microscopic cytochemistry of pseudo-Chediak-Higashi granules in 5 cases of AML]. AB - Blasts from 5 cases of AML with pseudo-Chediak-Higashi granules were examined ultrastructurally and histocytochemically using peroxidase, acid phosphatase, high iron diamine (HID) and periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) stainings. Pseudo-Chediak-Higashi granules, which appeared as vacuole like inclusions by light microscopy, generally contained electron-lucent materials. All pseudo-Chediak-Higashi granules were, positive for peroxidase but some were negative for acid phosphatase. Pseudo-Chediak-Higashi granules were HID positive, indicating that they contained sulfated glycoconjugates. Glycogen-like particles were observed in the pseudo-Chediak-Higashi granules with the PA-TCH-SP method, as occasionally observed in granules in drug resistant ALL blasts. In conclusion, the contents of pseudo-Chediak-Higashi granules, which seems to be formed by fusion of small granules, differed from those of normal azurophillic granules. PMID- 2214173 TI - [Acute lymphocytic leukemia with thrombophlebitis of lower limbs and translocation (4;11)]. AB - On November 22, 1985, a 54-year-old male was admitted to the cardiovascular department of our hospital suffering from thrombophlebitis, with redness, swelling and pain around the right ankle and left knee. He was transferred to our department on Nov. 26, because of hyperleukocytosis. Peripheral blood examination revealed hyperleukocytosis with 93.0% blastic cells and thrombocytopenia. The bone marrow aspirate was hypercellular and almost all cells were consistent with peroxidase negative blastic cells. The blastic cells were Leu M1 positive and Leu M2, M3 and lymphocytic markers were negative. The patient was diagnosed to have acute lymphocytic leukemia with Leu M1 positive blast cells. BH-AC/DMP therapy was began on the 1st hospital day but he died of cerebral haemorrhage on the 4th hospital day. An autopsy revealed systemic infiltration of leukemic cells including thrombophlebitis of the legs. Chromosome analysis of the bone marrow cells showed t(4;11)(q21;q23). PMID- 2214172 TI - [Treatment of acute lymphoblastic leukemia in adults by the modified protocol of L-10M (Sloan-Kettering)]. AB - We have treated 20 adult patients with acute lymphoblastic leukemia (ALL) and 2 patients with lymphoblastic lymphoma with a protocol modified from L-10M of the Memorial Sloan Kettering Cancer Center. Eighteen patients (81.8%) entered complete remission (CR). Eight of them eventually relapsed (only 1 patient had a meningeal relapse) and died. Median CR duration was 19 months (median overall follow-up of 35 months and 50% remission duration was not yet determined. Median overall survival was 19 months. Three patients died of sepsis during remission induction, but all of other deaths were due to resistant or relapsed leukemia. The four patients who completed 3.5 year's modified L-10M protocol were free from relapse for 6-11 months (mean 8.7). Although further follow-up is necessary, we suggest that modified L-10M protocol is effective for adult ALL and long-term survival may be available. PMID- 2214174 TI - [A latent form of essential thrombocythemia presented as portal hypertension and associated with acquired von Willebrand syndrome]. AB - A 32 year-old male patient was admitted to our hospital because of abdominal tumor. The examination on admission showed massive splenomegaly and esophageal varices although peripheral blood cell counts were within normal limits. Exploratory laparotomy was performed with the diagnosis of portal hypertension and revealed the multiple thrombus formations in the splenic vein and the extramedullary hematopoietic findings in the spleen by the microscopic examination. In vitro colony forming assay showed the formation of spontaneous erythroid colonies in cultures of progenitor cells (from peripheral blood mononuclear cells) in erythropoietin-poor medium. Increasing thrombocytosis was observed immediately after splenectomy, and hemorrhagic diathesis of nasal bleeding and gastrointestinal bleeding were also detected. The analysis of plasma von Willebrand factor (vWF) revealed the decrease of ristocetin cofactor activity and the lack of large multimeric components of vWF. These abnormal findings observed after splenectomy led to recovery through the administration of busulfan with the improvement of thrombocytosis. Accordingly, the course of the disease clearly indicated it to be the essential thrombocythemia represented as portal vein thrombosis and in latent form with normal cell counts in peripheral blood at the time of diagnosis, and subsequently, to develop into a full-blown form associated with acquired von Willebrand syndrome following splenectomy. PMID- 2214175 TI - [Nonproducing myeloma without evident bone lesion]. AB - A 76-year-old female was admitted to our hospital because of anemia. Complete blood count was as follows: RBC 2.37 X 10(6)/microliters, Hb 7.7 g/dl, WBC 2,600/microliters, Plt 105 X 10(3)/microliters. A bone marrow aspirate revealed 40.8% plasmacytoid cells showing the characteristics of plasma cells by electron microscopy. Total serum protein was 5.4 g/dl. Monoclonal protein was not observed by electrophoresis. On immunoelectrophoresis, M-bow was not observed in the serum or in 50-fold concentrated urine. The plasma cells were negative for cytoplasmic IgG, M, A, E, D, kappa or lambda by immunoperoxidase studies. Although radiologic studies of the bones did not reveal destructive or punched out lesions, we diagnosed this case as a nonproducing myeloma and the patient responded to MP therapy. This case was considered interesting as regards the pathological entity of myeloma. PMID- 2214176 TI - [Complete remission in multiple myeloma with natural interferon-alpha (HLBI) and melphalan/prednisolone intermittent therapy]. AB - A 46-year-old man was admitted because of lumbago and numbness of the left leg. Pelvic X-ray showed a large defect in the left sacrum and CT revealed multiple punched-out lesions. Serum IgA was 1,740 mg/dl with a monoclonal component of IgA kappa by serum electroimmunofixation. Bence Jones protein of kappa type was detected in urine. Diagnosis of myeloma was made on the basis of histology of the biopsied sacral tumor. Repeated melphalan/prednisolone intermittent therapy (MP) was done with concomitant administration of natural interferon-alpha (IFN-alpha) 3 X 10(6) U intramuscularly for 67 days. Performance status including gait markedly improved. Normal bone marrow morphology and disappearance of M-protein by electroimmunofixation were achieved after 13 cycles of MP, when pelvic X-ray revealed prominent recalcification. No further treatment was instituted for subsequent 6 months, without any demonstrable M-protein. Complete remission of myeloma is rare with conventional therapies and thus new therapeutic modalities have been waited for. IFN-alpha may promise better responses if appropriately combined with other chemotherapies. PMID- 2214177 TI - [Acute myelomonocytic leukemia with Inv(16) (p13 q22) relapsed in transverse myelopathy]. AB - We report a case of AML (M 4) with eosinophilia who developed meningeal relapse and transverse myelopathy. A 37-year-old woman was admitted to our hospital because of lymphadenopathy and ecchymosis. One week prior to admission, she noticed swelling of the cervical lymph nodes and bleeding tendency. On admission, low-grade fever, gingival swelling, generalized lymphadenopathy, and ecchymosis on the lower legs were found. A white blood cell count was 93,900/microliters with 82% blast cells, and a platelet count was 24,000/microliters. A bone marrow was composed of 45.3% myeloblasts, 27% monocytes and 7.1% eosinophils. Chromosome analysis revealed inv(16). The diagnosis of M4Eo was made. About one year after she gained complete remission, she was readmitted because of disturbance of urination. There was a sign of transverse myelopathy at the seventh vertebral level, and blast cells were detected in the cerebrospinal fluid. Despite of radiation and chemotherapy, paresis of lower extremities and sensory disturbance were persistent, and the patient died on 52th hospital day. PMID- 2214178 TI - [Successful ATG and bolus methylprednisolone therapy towards severe aplastic anemia with splenomegaly]. AB - A 22-year-old female patient with severe aplastic anemia was treated by ATG.bolus methylprednisolone therapy. After the therapy, anemia and thrombocytopenia began to recover within a month. The frequency of blood transfusion decreased thereafter. Since anemia due to splenomegaly was certified, bolus methylprednisolone therapy was performed in good response. Suppressor T-cells towards hemopoiesis were confirmed in this case, and hemopoietic potential was augmented by ATG.bolus methylprednisolone therapy. In spite of discontinuation of any therapy in 1986, she is being in good health more than five years. PMID- 2214179 TI - [Atypical infiltration of megakaryocytes into the liver and spleen in a case of refractory anemia]. AB - A 72-year-old man was admitted to our hospital because of general malaise. The peripheral blood showed pancytopenia (WBC 800/microliters, RBC 970,000/microliters, Plt 95,000/microliters). The bone marrow smear revealed morphological abnormalities in three lineage without increase in blasts. He was diagnosed as having myelodysplastic syndrome (MDS). He was treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) for leukopenia, and with washed RBC transfusions for anemia. Eight months after diagnosis of MDS, blastic cells increased in peripheral blood and bone marrow showing overt leukemic state. He died of pneumonia. An autopsy revealed that atypical megakaryocytes increased in bone marrow and infiltrated into the spleen and liver. This case suggests that not only blasts but also megakaryocytes infiltrate into extramedullary organs in some cases of MDS. PMID- 2214180 TI - [Myelofibrosis associated with immunological abnormalities]. AB - A 74-year-old man was admitted to the National Defense Medical College Hospital because of purpura on the extremities. The blood hemoglobin level was 11.5 g/dl, the white blood cell count 7. 3 x 10(9)/l with 3% blastic cells, and the platelet count 4.0 x 10(9)/l. There was leukoerythroblastosis with only mild teardrop appearance of erythrocytes. The blastic cells consisted of two types, megakaryoblast-like cells and myeloblast-like cells. There was a very mild hepatosplenomegaly, but no lymphadenopathies. The bone marrow aspirations yielded dry taps. The marrow biopsy specimen revealed myelofibrosis associated with trilineage hyperplasia, but no apparent infiltration of leukemic cells. Platelet associated IgG (PAIgG) had a high titer and the response to platelet transfusions was poor. On prednisolone and colchicine, the blastic cells in the peripheral blood disappeared and the platelet count increased. He died of pneumonia. The autopsy showed myelofibrosis with hyperplasia of myeloid and erythroid lineage in the bone marrow. Megakaryocytes were relatively few and there was no infiltration of leukemic cells. PMID- 2214181 TI - [One-year remission of chronic myelogenous leukemia (CML) after discontinuation of interferon-alpha]. AB - A 53-year-old woman was admitted to our hospital on Nov. 16, 1987, because of general fatigue. On admission, she had hepatosplenomegaly and her peripheral blood profile showed a white blood cell count (WBC) of 309 x 10(3)/microliters with immature neutrophils, a hemoglobin level (Hb) of 7.6 g/dl, platelet count (PLT) of 536 x 10(3)/microliters, neutrophilic alkaline phosphatase (NAP) score of 44. Both Vitamin B12 and LDH levels were high. The bone marrow showed marked myeloid hyperplasia. In a cytogenetic study, Ph1 was found in 3 of 8 metaphases and Ph1 with an additional abnormality of 8 trisomy was noted in 5 of 8 metaphases. She was diagnosed as having chronic myelogenous leukemia (CML) and treated by i.m. injection of interferon (IFN)-alpha at a daily dose of 6 x 10(6) U. Administration of IFN-alpha induced fever for a few days. WBC, PLT count and LDH level gradually decreased, and the NAP score and hepatosplenomegaly improved. She achieved remission in February, 1988. Administration of IFN-alpha was stopped in April, 1988, when the bone marrow showed hypocellularity and normal karyotype. She was treated with 20 mg of prednisolone daily from May until August, because of progressive pancytopenia. She had received no treatment until July, 1989. In May, 1989, the bone marrow again showed myeloid hyperplasia and Ph1 was found in all cells analyzed. Therefore, we resumed IFN-alpha treatment. It is interesting that remission of CML continues for more than one year after discontinuation of IFN-alpha in this case. PMID- 2214182 TI - [Blast crisis of chronic myelogenous leukemia with blasts expressing both immature B lymphocyte- and myelomonocyte-associated antigens and differentiating into basophils in vitro]. AB - A 43-year-old woman with Ph1-positive chronic myelogenous leukemia (CML) was diagnosed as having blastic crisis. The phenotype of blasts was CD9+, CD10+, CD19+, CD11b+ and CD33+, suggesting the B Lymphoid and myeloid mixed lineage. Two color analysis of CD10 and CD33 revealed that 50% of blast cells had both B lymphocyte- and myelomonocyte-associated surface markers. Rearrangement of the immunoglobulin heavy chain gene was detected. After culturing blasts with 12-o tetradecanoyl-phorbol 13 acetate (TPA), basophilic granules appeared in cytoplasm of the cells. These granules were positive for toluidine blue staining. This finding that the biphenotypic blasts expressing both B lymphoid and myelomonocytoid features differentiated into basophils suggests that blasts of this case are derived from a common progenitor of B lymphoid and myeloid lineages including basophil. PMID- 2214183 TI - [Macrothrombocytopenia with deafness, nephritis, cataract, short small intestine, and double ureter]. AB - A 23 year old female, born in 1957, was diagnosed as having idiopathic thrombocytopenic purpura at the age of 3 and treated with prednisolone during her childhood with no response. On her regular check-up in 1978, facial edema and proteinuria suggested renal disease. The family history was negative for bleeding diathesis or renal disease. Close examination revealed the following: WBC 4,200/microliters without leukocyte inclusions, RBC 3.42 x 10(6)/microliters, Hb 11.7 g/dl. PT 10.6 sec, APTT 28.9 sec. Platelet count 4,500/microliters by HEMATRAK 360, and 40 x 10(3)/microliters measured by microscopic method. Giant platelets were noted on peripheral blood smear with an average diameter of 6.1 microns. Bleeding time (Duke) was 12.0 min. Number of megakaryocytes was increased although platelet production was remarkably decreased. Results of platelet aggregation and retention tests were normal. Platelet life span (T1/2) was 2.3 days. Sensory neural hearing loss, congenital cataract, double ureter and short small intestine were also found. Chromosome analysis showed 46XX. She underwent splenectomy resulting in increase of the platelet count to 226 x 10(3)/microliters. The increased platelet count, however, gradually decreased to the initial count in 2 years although the bleeding tendency was improved. In 1987, renal function deteriorated, causing intractable hypertension. The serum creatinine was 4.8 mg/dl. The following year she developed cerebral bleeding and died 4 days after the episode. The serum creatinine was 8.6 mg/dl. PMID- 2214184 TI - [Occurrence of breast cancer, renal cancer and multiple myeloma in a Nagasaki atomic bomb survivor]. AB - A 60-year-old female, who was exposed to the Nagasaki atomic bomb at 18 years old, had renal cancer and subsequently was found to have multiple myeloma (IgG kappa). She underwent the left mastectomy for breast cancer at 43 years old but was not given chemotherapy and radiotherapy. The karyotype of bone marrow cells was 46, XX. The estimated radiation dose was under 10 rads. While the effect of such a low-dose of radiation is considered to be almost negligible, there would be a possibility that in this case the risk of carcinogenesis was enhanced as her age advanced. PMID- 2214185 TI - [Fetal survival after the corticosteroid and low-dose aspirin regimen in a case of anti-phospholipid antibody syndrome]. AB - A 27-year-old woman with anti-phospholipid antibody syndrome, whose first pregnancy had ended in intrauterine fetal death, was treated with prednisolone 0.6 mg/kg/day before second pregnancy. Suppression of anti-cardiolipin antibody activity was rapidly achieved and maintained during the pregnancy. After conception, low-dose aspirin 81 mg/day was started and continued until delivery. She gave birth to a normal live infant with natural full-term delivery. It is strongly suggested that the corticosteroid and low-dose aspirin regimen can lead to successful pregnancy in cases with anti-phospholipid antibody syndrome like the present case. PMID- 2214186 TI - [Increase of serum acidic isoferritins in patients with hemophagocytic histiocytosis]. AB - We investigated serum isoferritin patterns in 2 patients with reactive hemophagocytic histiocytosis (HH) and 1 patient with neoplastic HH (malignant histiocytosis) whose serum ferritin levels were extraordinarily high. Serum ferritins in 2 patients with reactive HH were composed of mildly (pI 5.55 to 5.10) to intermediately (pI 4.81 to 4.82) acidic isoferritins, while those in patient with neoplastic HH were composed of more acidic (pI 4.70 to 4.45) isoferritins. These results indicate that the main constituents of the increased serum ferritins in HH would be acidic isoferritins, and that more acidic isoferritins would be increased in neoplastic HH than reactive HH. PMID- 2214187 TI - [Diagnostic significance of the number of bone marrow megakaryocytes in cases with decreased platelet production evidenced by platelet kinetic study]. AB - In 18 patients with decreased platelet production proved by reduced platelet turnover, the numbers of megakaryocytes in clot section of marrow aspirate were counted. Platelet counts ranged from 19,000 to 128,000/microliters. The sternal marrow showed decrease of megakaryocytes only in 3 out of 18 cases while megakaryocytes in the iliac marrow were reduced in 6 out of 11 cases. Only one of 11 cases showed decrease of megakaryocyte in both marrows examined. On the contrary, four cases showed normal number of megakaryocytes at both sites. Of 9 cases with normal or increased number of megakaryocytes in sternal and/or iliac marrow, no case showed morphologically abnormal megakaryocytes and only one case had the reduced number of platelet-forming megakaryocytes. Results suggested that the number of megakaryocytes in bone marrow especially in the sternum was not reliable for establishing the diagnosis of decreased platelet production, and that about 50% of patients with thrombocytopenia due to hypoproduction of platelets could be diagnosed pertinently only after the study of platelet kinetics. PMID- 2214188 TI - [bcl-2 gene rearrangement and its expression in tumor cells]. AB - Both the rearrangement and the expression of the bcl-2 gene in Japanese hematopoietic tumor cells were studied by Southern and Northern blot hybridizations. The expression of the bcl-2 gene was studied in seven cultured cell lines and twenty clinical samples, including eleven non-lymphoid tumors and nine lymphoid tumors. All lymphoid tumors except one sample from a patient with ALL expressed the bcl-2 gene. The bcl-2 gene was strongly expressed in B cell tumors. This gene was also expressed in T-ALL samples studied, although the expression was not as marked as in the B cell tumors. Non-lymphoid tumors did not express bcl-2 gene. bcl-2 gene rearrangement was studied in five cultured cell lines and six clinical samples including four follicular lymphomas and two T ALLs. No abnormal bcl-2 gene configurations were found in any of the clinical samples. Among the cultured cell lines, the BALL-1 line showed two-fold amplification. The frequency of bcl-2 rearrangement in Japanese follicular lymphomas is reported to be lower than that seen in the American follicular lymphomas. Nevertheless, the increased expression of the bcl-2 gene seen in the Japanese B cell tumors studied supports the contention that the bcl-2 gene plays an important role in the pathogenesis of B cell tumors. PMID- 2214189 TI - [VAD chemotherapy of multiple myeloma]. AB - Twelve patients with resistant or recurrent multiple myeloma were treated with VAD regimen (vincristine, adriamycin, dexamethasone), first reported by Barlogie B et al 1984. Of 11 evaluable patients, 7 responded (partial response [PR] 3, minor response [MR] 4), and the overall response rate was 63.7%. The median interval to achieve remission was 27 days, and the median duration of remission was 125 days. One course seemed sufficient for the assessment of effectiveness of the VAD chemotherapy, because in all responders, over 50% reduction of monoclonal protein was obtained in the first course of chemotherapy. We also administered verapamil or trifluoperazine in addition to VAD in two patients who had acquired resistance to VAD. Both had MR. Side effects included infections, gastro intestinal bleeding, congestive heart failure or severe malaise. In conclusion, the VAD chemotherapy is effective but the duration of remission is short and side effects cannot be disregarded. Perspective of VAD and improvement of the management of refractory multiple myeloma is discussed. PMID- 2214190 TI - [The relationship between responsiveness to splenectomy and clinical course after splenectomy in chronic idiopathic thrombocytopenic purpura (ITP)]. AB - Fifty-four ITP patients were treated by the protocol proposed by Japanese Idiopathic Disease of Hematopoietic Organ Research Committee. Forty-eight patients were treated with corticosteroid (CS). Twenty-eight patients out of 30 patients who were refractory to CS were splenectomized. To study natural courses of splenectomized patients, 25 patients were splenectomized without elevation of platelet counts at the operation and were followed up their platelet counts and PAIgG for one month without treatment. Clinical courses after splenectomy were classified into four types by the platelet increment followed by splenectomy and the platelet counts at one month after splenectomy; type I (markedly over-shooted platelet peak and normalized platelet counts), type II (moderate platelet peak and 50 approximately 100 x 10(3)/microliters platelets), type III (minimal platelet peak and less than 50 x 10(3)/microliters platelets), and type IV (elevation of platelet counts at day 7 or later of splenectomy and normalized platelet counts). The results of analyses from 25 patients indicated that the numbers of type I, II, III and IV were 10, 5, 6 and 4, respectively. The clinical course of type IV suggests that platelet production may be impaired by anti platelet antibodies. PMID- 2214191 TI - [Occurrence of cytoplasmic bridge between erythroblasts--morphology and frequency in hematological disease]. AB - Peculiar cytoplasmic connection between erythroblasts was observed in the smear preparation of human bone marrow; a pair of erythroblasts in the resting stage was connected by "cytoplasmic bridge" which is very thin and sometimes long compared with the telophase bridge appeared in the usual cytokinesis. Electron microscopy revealed that small amount of microtubules were running along in the cytoplasmic bridge but mid-body was not seen. Plasma membrane about the middle of the bridge bulged to form "bulging ring". Erythroblasts in various differentiating stages were connected by the cytoplasmic bridge and the stage of each pair was almost the same. The occurrence of the cytoplasmic bridge between erythroblasts was evaluated in the smear preparations of human bone marrow with hematological diseases or normal conditions. In the normal bone marrow, the mean value was 8.1 +/- 3.6% (n = 33). In patients suffered from autoimmune hemolytic anemia, it was 4.3 +/- 2.3% (n = 12), aplastic anemia, 3.2 +/- 2.1% (n = 6) and paroxysmal nocturnal hemoglobinuria, 5.0 +/- 1.4% (n = 3). While in the erythroleukemia the occurrence was very low showing 0.2 +/- 0.1% (n = 3) of total erythroblasts. In MDS, RAEB (2.5 +/- 2.4%) and RA (2.9 +/- 2.2+%) showed statistically significant lower occurrence. In the normal bone marrow the occurrence was higher, so the formation of cytoplasmic bridge could be essential for a normal proliferation of erythroblasts. PMID- 2214192 TI - [Angio-immunoblastic lymphadenopathy with fibrosis of bone marrow, lymph node, liver and spleen, and proliferation of epithelioid cells in lymph nodes]. AB - We report a 47-year-old man diagnosed as angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) with fibrosis of the bone marrow, lymph node, liver and spleen, and proliferation of epithelioid cells in lymph node. He was admitted to a hospital in May, 1980 because of general fatigue, cough, fever and systemic lymphadenopathy. The diagnosis of AILD was based on a biopsy of right cervical lymph node. His symptoms were improved but recurred with the addition of icterus and progressive pancytopenia with decrement of prednisolone. He was referred to our hospital in July, 1980 and his physical examination revealed generalized lymphadenopathy, icterus and hepatosplenomegaly. Hemogram showed pancytopenia, and needle biopsy of the bone marrow disclosed fibrosis. Sections from the lymph node showed AILD with proliferation of epithelioid cells. Administration of 60 mg/day of prednisolone improved the fever, lymphadenopathy and hepatosplenomegaly. However he died suddenly of acute respiratory failure on July 30. Autopsy showed fibrosis of bone marrow, lymph node, liver and spleen with infiltration of abnormal lymphocytes, and pulmonary aspergillosis. PMID- 2214193 TI - [An erythremia with acquired HbH disease and chromosomal abnormality]. AB - A 56-year-old male was admitted to the Nihon University Hospital because of general fatigue and anemia on September 21st, 1985. He had mild hepato splenomegaly. Hematological findings showed RBC 286 x 10(4)/microliters, Hb 6.0/dl, reticulocyte count 2.5%, platelet count 9.3 x 10(4)/microliters and WBC 2,400/microliters. An erythroblast per 100 leukocytes counted in a blood film was found. Bone marrow was erythroid hyperplasia with megaloblasts. The erythroblasts were PAS positive but not ringed sideroblasts. Other laboratory data including hemolysis were all negative. This case seemed to be diagnosed as refractory anemia (RA) according to the FAB classification. Chromosomal analysis of marrow cells, however, all revealed 46, XY, 20q- at diagnosis and 46, XY, 7q- 20q- after 22 months. Furthermore, Hb electrophoresis ahd family study indicated the presence of acquired HbH disease. Neither erythroid bursts (BFU-e) nor late erythroid progenitors (CFU-e) were detected. He has had progressive anemia without proliferation of blasts for over 2 years. From these findings, we postulate that the entity of erythremia should be distinguished from RA including many heterogeneous diseases. PMID- 2214194 TI - [Bone marrow re-transplantation following a busulfan and cyclophosphamide regimen]. AB - A 36-year-old man was diagnosed as having RAEB in 1986, and required blood transfusion regularly because of severe anemia. He received the first bone marrow transplantation following total-body irradiation and etoposide infusion in October 1987. He was found to be relapsed into RAEB on 106th day after BMT. And the second BMT was planned. According to the conditioning regimen of Tutschka, et al, we administrated busulfan and cyclophosphamide before re-transplantation. On 26th day after BMT, the WBC count exceeded 1,000/microliters and anemia was improved, while thrombocytopenia persisted until 50th day. Normal hematopoiesis in the bone marrow was confirmed on the 29th day. No severe side effect except for a little fevering and bleeding was found during the clinical course. Unfortunately he died of pneumonia following graft versus host disease on the 166th day after re-BMT. This new conditioning regimen is considered to be a choice for the high risk patients on re-transplantation. PMID- 2214195 TI - [Acute myeloblastic leukemia associated with 46, XY, del(5)(q22)]. AB - A 38-year-old male admitted to the Internal Medicine of Surugadai Nihon University Hospital, complaining of general fatigue and throat pain. The laboratory examinations revealed leukocytosis (83, 900/microliters) and an appearance of myeloblasts (90.2%) in the peripheral blood. The nucleated cell count was 56 x 10(4)/microliters with 85.5% myeloblasts in bone marrow. He was diagnosed as acute myeloblastic leukemia (AML). Though he received two courses of combination chemotherapy with daunorubicin, BH-AC, 6 MP and prednisone, one course of combination with mitoxantrone, etoposide and cytosine arabinoside and one course of combination with aclarubicin cytosine arabinoside and prednisone, he could not achieved remission. A chromosome analysis revealed 46, XY del(5)(q22). The amount of DNA fragments hybridized to 4.5 Kb v-fms probe in blastoid cells was approximately a half amount of normal persons. It is not defined the relationship between the decrease of fms and leukemia in this case. He was diagnosed de novo AML, since he had not been received the therapy with potential mutagenic and carcinogenic agents and had not been exposed the irradiation on his works. PMID- 2214196 TI - [Myelodysplastic syndrome in a child which developed into megakaryocytic leukemia with late appearing Ph1 chromosome and rearrangement of breakpoint cluster region]. AB - A 3-year-old boy was referred to our hospital in September 1985, because of pancytopenia. His bone marrow was normocellular with 18% blasts, which had Auer rod and were positive for peroxidase staining. A diagnosis of refractory anemia with excess blasts in transformation was made according to FAB criteria. Chromosome analysis of bone marrow cells showed normal male karyotype. He attained complete remission with aclarubicin and BH-AC and continued it until August 1987 when pancytopenia and hypoplastic bone marrow developed. Chromosome analysis of bone marrow cells showed normal male karyotype and gene analysis revealed germ-line configuration of breakpoint cluster region (bcr). Overt leukemia developed in May 1988 when his WBC count increased to 60, 600/microliters with 91% blasts, which were negative for peroxidase staining, positive for anti-Ia and CDw 41 by cell surface analysis, and positive for ultrastructurally demonstrable platelet peroxidase. A diagnosis of megakaryocytic leukemia was made. Chromosome analysis of bone marrow cells showed 46, XY, t(9;22) (q34;q11) and gene analysis revealed rearrangement of bcr. He died in November 1988. Our results and review of literature suggest that late appearing ph1 chromosome and rearrangement of bcr may occur in a variety of hematologic malignancies and influence the course of disease. PMID- 2214197 TI - [Lymphoproliferative disorders]. PMID- 2214198 TI - [Structures and heterogeneity of immunoglobulins]. PMID- 2214199 TI - [General aspects of cytokines]. PMID- 2214200 TI - [Complement and bio-phylaxis]. PMID- 2214201 TI - [Review on the immune complex]. PMID- 2214202 TI - [Concept of autoimmune disease]. PMID- 2214203 TI - [Origin and differentiation of the cells operation immune functions]. PMID- 2214204 TI - [Immunologic deficiency syndromes]. PMID- 2214205 TI - [Protective immunity for infection]. PMID- 2214206 TI - [Gene engineering]. PMID- 2214207 TI - [Cell engineering]. PMID- 2214208 TI - [Detection of bacterial toxin genes by the DNA colony hybridization]. PMID- 2214209 TI - [DNA transformation]. PMID- 2214210 TI - [DNA Data Bank]. PMID- 2214211 TI - [Detection of DNA polymorphisms]. PMID- 2214212 TI - [Genetic aspects of hyperlipidemia]. PMID- 2214213 TI - [DNA diagnosis of amyloidoses]. PMID- 2214214 TI - [Application of non-RI-labeled DNA probes to diagnosis]. PMID- 2214215 TI - [Analysis of brain CT in 120 patients with human cysticercosis]. AB - A study on brain CT was made in 120 patients of human cysticercosis, which is a rare disease in Japan and clinical symptoms and laboratory data for the diagnosis were also discussed. From the point of therapeutic view, we proposed a new differentiation on brain CT of human cysticercosis, which is divided into two groups according to the alive or dead parasite. Furthermore, we proposed a new type named multiple large and small cysts type on brain CT. The idea of diagnostic standard was made integrating brain CT image, clinical symptoms and laboratory data. PMID- 2214216 TI - [MR imaging of internal carotid artery occlusion]. AB - Five patients with internal carotid artery occlusion were studied with MR imaging at 0.22 T. At the carotid siphon, occluded vessels showed absence of flow void in three patients. But two cases had "partial flow void" which mimicked small arterial caliber. In these patients angiography showed collateral circulation to the carotid siphon. So the partial flow void in the carotid siphon suggested internal carotid artery occlusion with collateral circulation. PMID- 2214217 TI - [A comparison study of SPECT and MRI in remote effects of chronic cerebrovascular disease]. AB - A comparison study of SPECT and MRI was performed to investigate remote effects in 10 patients with chronic cerebrovascular disease. Hypoperfusion in the cerebellar hemisphere contralateral to supratentorial lesions, the overlying cerebral cortex ipsilateral to subcortical lesions, the thalamus ipsilateral to cortical lesions, and the visual cortex distant to optic radiation lesions was demonstrated using SPECT with 123I-IMP. Although hypoperfusion in these remote areas was considered to be related to irreversible degenerative processes in the chronic phase, MR images did not reveal any abnormalities. PMID- 2214218 TI - [CT in colon cancer]. AB - CT pictures from 59 lesions of advanced colon cancer including rectal cancer were reviewed to evaluate a role of CT in preoperative staging diagnosis. CT findings were recorded following general rules for clinical and pathological studies on cancer of colon, rectum and anus, proposed by Japanese Society for Cancer of Colon and Rectum. 1) Tumors were detected in 90% of advanced colon cancers. 2) Sensitivity in local extension (S factor) was 58.0%. 3) Sensitivity in lymph node involvement (N factor) was 50.0%. 4) Sensitivity in final staging diagnosis, dividing colon cancer into two groups below st II and above st III, was 63.3%. 5) Further study should be necessitated to provide useful information for preoperative staging diagnosis of colon cancer. PMID- 2214219 TI - [Studies on the roentgenological differentiation between complex and simple bowel obstruction]. AB - We studied 81 cases of organic bowel obstruction. In complex obstruction 7 cases out of 25 (28%) were diagnosed on the plain film before operation, although in simple obstruction 54 cases out of 56 (96%). But in retrospective evaluation of the plain films, we noticed that in some cases of complex obstruction, marked small bowel obstruction and ascites were seen from the onset, which were never seen in simple obstruction. We considered this finding as the key point for the roentgenological differentiation between complex and simple obstruction. PMID- 2214220 TI - [Diagnostic imaging of cystic pancreatic tumors]. AB - Five cases of pathologically proved cystic pancreatic tumors were retrospectively reviewed. Mucinous cystadenocarcinoma tends to have uneven wall or solid mass component. All cystic lesions without history of acute pancreatitis or trauma should be surgically removed, even when considered as benign on imaging modalities. PMID- 2214221 TI - [Diagnosis of the pelvic fracture which requires TAE on plain pelvic radiograph]. AB - We reviewed the initial emergency-room plain pelvic radiographs of 75 patients with pelvic fracture. In thirty-six patients transcatheter arterial embolization (TAE) was performed for retroperitoneal hemorrhage associated with pelvic fracture (TAE group) and in 39 patients (non-shock group) TAE was not required. In TAE group, fractures involving iliosacral region and pubic symphysis were more dominant than in non-shock group. Specific soft tissue abnormal shadow of TAE group was not present. It may be impossible to determine the necessity of TAE in pelvic fracture on the basis of plain pelvic radiograph. PMID- 2214222 TI - [Insufficiency fracture of the sacrum]. AB - Three cases of insufficiency fracture of the sacrum are reported. Cortical disruption and linear sclerosis with or without linear fracture line at the upper sacral segment parallel to the sacroiliac joint are characteristic. Bone scintigram is suitable for screening, but plain radiographic and CT findings are diagnostic. Insufficiency fracture of the sacrum should not be confused with other conditions, such as metastatic disease. PMID- 2214224 TI - [Fractionated irradiation with special reference to head and neck tumors]. PMID- 2214223 TI - [Azygous continuation of the inferior vena cava (a congenital defect of the inferior vena cava)]. PMID- 2214225 TI - [Atypical computed tomographic appearance of herpes simplex encephalitis]. AB - In cases of herpes simplex encephalitis, a low density lesion in the temporal lobe is a common CT finding, whereas hemorrhagic lesion is rarely observed on CT in this disorder despite the frequent occurrence on pathologic studies. Two cases of hemorrhagic lesion observed on CT in herpes simplex encephalitis are reported, and atypical CT findings of herpes simplex encephalitis is discussed. PMID- 2214226 TI - [Interhemispheric cyst of an adult associated with partial agenesis of the corpus callosum]. AB - The authors report an adult patient with an asymptomatic interhemispheric cyst demonstrated by computerized tomography (CT), magnetic resonance imaging (MRI) scan and angiography. Partial agenesis of the corpus callosum is associated. PMID- 2214227 TI - [A case of pseudoinfarct of the liver (Zahn's infarct)]. AB - We reported a case of pseudoinfarct (Zahn's infarct) of the liver caused by the inflammatory pseudotumor. A dense segmental staining in the area of Zahn's infarct, which was thought to be characteristic finding, was found on the hepatic angiography. This finding was supposed to be consistent with sinusoidal hyperemia according to the pathological finding. PMID- 2214228 TI - [A case of giant cavernous hemangioma with hemoperitoneum due to blunt abdominal trauma; CT findings]. AB - A 55-year-old woman with a giant cavernous hemangioma in the liver with hemoperitoneum due to blunt abdominal trauma was reported. CT findings of the liver at first thought to be hepatic injuries. But serial studies revealed that the CT findings were dependent on giant cavernous hemangioma and apart from hepatic injury. PMID- 2214229 TI - [Transarterial embolization of metastatic pheochromocytoma]. AB - We successfully controlled hypertension of a 48-year-old female by embolizing metastatic pheochromocytoma of the liver. Although transarterial embolization of the hepatic artery was uneventful, the patient soon developed severe hypertension and tachycardia which were controlled medically. Symptoms subsided within 10-20 days. Follow-up CT showed reduction of the liver mass. PMID- 2214230 TI - [A case of extramedullary plasmacytoma of the mesenteric lymph nodes]. AB - Reported here is a extremely rare case of extramedullary plasmacytoma which occurred in the mesenteric lymph nodes and could be diagnosed before operation. The ultrasound examination showed a multilobular mass, the CT examination a multilobular, homogeneous mass, and angiography a hypervascular lesion. M-protein decreased after operation. PMID- 2214231 TI - [A case of myxadenoma of the renal capsule]. AB - We reported the case of a 69-year-old man who had resection of a myxadenoma of the renal capsule. The tumor measured 28 x 24 x 6.5 cm and weighed 3,000 grams including the left kidney. CT was useful in suggesting the diagnosis of the renal capsular tumor. PMID- 2214232 TI - [A case of bilateral adrenal myelolipoma]. AB - We reported a case of bilateral adrenal myelolipoma. Low height, obesity and and elevation of 17-KS were found in this case. Tumors were hypovascular adrenal masses with low attenuation numbers on CT. MRI was useful in demonstrating the relation of tumors to adjacent organs. It should be considered that, although very rare, bilateral myelolipoma is possible. PMID- 2214233 TI - [The development of a modified J-shaped long sheath and its application]. PMID- 2214234 TI - [Fibronectin binding to Staphylococcus aureus in experimental staphylococcal skin infection in mice]. AB - Staphylococcus aureus infection of skin was produced in cyclophosphamide-treated mice by intracutaneous inoculation of a strain in this organism clinically isolated from a carbuncle. Deposition and binding of fibronectin in initial stage of the infection were followed by immunohistochemistry and immunoelectron microscopy. Fibronectin began to deposit in a fine granular pattern in the dermis and musculocutaneous layer at 2 minutes after the inoculation and gradually increased with time. Fibronectin binding on the surface of staphylococcal cells was seen after 12 hours of inoculation. At 24 hours two patterns of binding were seen. In one pattern, fibronectin was bound to a part of the cell surface of the microorganisms. The fibronectin binding parts were seen very close or attached to the fibrin-like-structure and dermal connective tissues. This suggests that fibronectin helped staphylococcus cells to attach to fibrin or connective tissues. The other pattern of fibronectin binding was the binding of fibronectin all around the cells. This pattern could be interpreted as inhibition by fibronectin of staphylococcus attachment to the fibrins and the tissues. PMID- 2214235 TI - [A sensitization effect of hematoporphyrin oligomer (HpO) and caffeine for X-ray radiation of skin cancer]. AB - Human malignant melanoma cells (G-361) were irradiated with X-ray for different irradiation times. The amount of DNA damage was much increased by the treatment of the cells with HpO before X-ray irradiation. Furthermore, it was found that the caffeine inhibited effectively the repair of the damaged DNA. Furthermore, HpO was administered before X-ray irradiation of transplantable skin tumor in C3H mice and/or caffeine+ was to be given the mouse after X-ray irradiation. The growth of the tumor irradiated with HpO and/or caffeine was more inhibited and the necrotic area was more expanded than that of the tumor irradiated X-ray only. Labeling Index utilizing bromodeoxyuridine (BrdU) in the viable area of the treated tumor decreased when HpO and/or caffeine were administered. The amount of DNA damage more increased in the tumor cells irradiated with HpO than that irradiated only. And, the repair of the damaged DNA was more delayed in the tumor cells irradiated with HpO and caffeine than that irradiated with the other treatments. In conclusion, it was considered that HpO might be a radioactive sensitizer and caffeine enhanced the inhibition of the repair of DNA damaged. We hope that the treatment of X-ray radiation with HpO and caffeine is useful for clinical treatment of human malignant tumor. PMID- 2214236 TI - [The correlations of respiratory function tests, chest roentgenographic manifestations and respiratory symptoms in the patients with systemic sclerosis, using a scoring-method for symptoms]. AB - Analytical studies were performed on the respiratory symptoms in 31 systemic sclerosis cases. Respiratory symptoms were expressed by scores from 1) coughs, 2) difficulties in walking, 3) difficulties in ascending, 4) dyspnea . In early stage cases with slight clinical symptoms, %VC was always normal, but %DLco was generally reduced. Because of good correlation between respiratory functions and clinical symptom scores, it is available to use the scores as well as %DLLco and %VC to diagnose slight lung involvement in systemic sclerosis. Also the clinical symptom scores are related to the roentgenographic manifestations of lung fibrosis which are characteristic in systemic sclerosis. Therefore we felt that this system of clinical symptom scores was useful to follow-up the patients. PMID- 2214237 TI - [Histological study of the oral mucosa of PSS]. AB - Histological examination was performed on the oral mucosa of 25 patients with PSS which consisted of 16 cases of Acrosclerotic type (A type) and 9 cases of Diffuse type (D type). Results obtained were as follows: (A) Sclerotic change of connective tissue were found in the submucosal area (a type) and in the salivary peri-glandular++ area (b type) and also in the both areas (c type). (1) In A type of PSS, sclerotic changes was found in 14 out of 16 cases (87.5%) and (2) In D type, 9 out of 9 cases (100%). (3) In D type, sclerotic changes were marked and, moreover, found in the earlier stage of disease more than in A type. (B) Inflammatory change of salivary gland based on the criteria of Chisholm and Mason. (1) Moderate and marked salivary gland adenitis were found in 6 out of 16 cases of A type (37.5%) and 2 out of 9 cases of D type (22%). (2) Adenitis were found more frequently in the early stage of disease in both types. From above described findings, it is concluded that 1) as to sclerotic change, the early and marked changes were found in D type and 2) as to inflammation of salivary gland, no significant difference was found between both types. PMID- 2214238 TI - [Cutaneous atypical mycobacteriosis due to Mycobacterium kansasii--a case report and a review of the literature]. AB - A case of cutaneous atypical mycobacteriosis due to Mycobacterium (M.) kansasii is reported. A 41-year-old man, who had lived in Kawasaki city, was seen in April 1988 because of sores on the dorsum of left forefinger which had been present for one month. Physical examination revealed an erythematous, edematous plaque approximately 2 and 4 cm overlying proximal and middle phalanx of left index finger. Otherwise his physical findings were normal. Laboratory studies including X-ray examinations of the chest and left hand were normal. The histopathology revealed a mixed cellular infiltration consists of mononuclear cells and neutrophils with necrosis in the dermis. No granuloma formation was observed. In the deep dermis, some acid fast bacilli (AFB) were demonstrated. The culture for AFB was positive with the following characteristics: Acidfastness (+), Niacin ( ), Photochromogenecity (+), Growth at 37 degrees C (+), at 42 degrees C (+), at 45 degrees C (-), Nitrate reduction (+), Catalase (+). These tests were diagnostic of Group I photochromogen, M. kansasii. We reviewed 19 cases of cutaneous atypical mycobacteriosis due to M. kansasii in the world literature including our case and found that there were three types of the disease: (1) Cutaneous chronic granulomatous type, (2) Disseminated acute pyogenic type and (3) Cutaneous pyogenic type. PMID- 2214239 TI - [A case of mixed connective tissue disease associated with uncommon acute myopathy caused by isolated muscle epithelioid granuloma]. AB - The patient is 48 year-old female who has been followed as MCTD with nonsteroidal therapies for 18 years. Sometimes she has been attached by focal severe muscle pain. One year ago, she had general myalgia associated with high fever and arthralgia. The results of the examination, aldolase, GOT, GPT, gamma-GTP, CRP and leucocyte were increased. Muscle biopsy showed noncaseating epithelioid granuloma being in contact with enlarged injected vessels. Out of tough with granuloma, a few fibre necroses, fibrosis of muscle, and degeneration of collagen fiber were recognized. After treatment of nonsteroidal antiinflammatory agents, her every complain was removed. Her muscle looks normal herself. MCTD has myopathy caused by inflammatory infiltrates and fibre necroses. But granulomatous myositis is very rare. It is difficult to differentiate our case from sarcoidosis, especially acute isolated muscle sarcoidosis. PMID- 2214240 TI - [The purification of high molecular weight protease from the rat's skin]. AB - In this study, the purification of a high molecular weight protease from Wistar Rats' skin was investigated. A high molecular weight protease from Wistar Rats' skin was purified by successive (NH4)2SO4 fractionation, Phenylsepharose CL-4B, and HPLC gel filtration chromatographies. The activity of the enzyme was determined using a synthetic substrate, succinyl-leucyl-leucyl-valyl-tyrosine methylcoumarinamide (SLLVT-MCA). The molecular weight of the purified enzyme was estimated to be 750,000 by gel filtration. With SDS-PAGE the purified enzyme was dissociated into several bands of which the majority fell into the range of 20,100-36,000 daltons. These findings suggest that high molecular weight protease in rat's skin consists of various subunits. PMID- 2214241 TI - [Clinical features of male SLE patients--summary of our 22 cases]. AB - We investigated clinical features of our 22 male SLE patients with main respect to 11 articles of ARA criteria for diagnosis of SLE (1982). As for skin lesions, 14 cases (64%) manifested wide spread discoid lupus erythematosus as their first symptoms, however, rather rare lesions could be seen as follows: 3 cases with nodular cutaneous lupus mucinosis, 1 with vesiculobullous LE. As to visceral manifestations, renal involvements could be seen in 11 cases (50%), among which 6 showed nephrotic syndromes. In immunological examinations, 1 case revealed C4A deficiency. The clinical tendency of male SLE cases has not been settled by now, for the disease is uncommon in men. Each of our 22 cases manifested a variety of features respectively, indicating that rather atypical cases as SLE can be more often seen in males than females. In addition, many of our cases showed remarkable changes clinically during their courses, which suggests that we should follow them carefully from now. PMID- 2214242 TI - [A study on the therapy and prognosis of pemphigus vulgaris]. AB - The treatment and, in particular, the prognosis of 32 patients with pemphigus were studied. All cases were classified according to treatment, for example, corticosteroid only, corticosteroid + immune-suppressive agents, plasma exchange + corticosteroid and/or immune-suppressive agents, and other treatments. Results showed that with the plasma exchange group skin lesions disappeared the quickest, the percentage of disappearance was the highest and a long standing remission was able to be maintained. With the plasma exchange group, many cases were severe and had complications which were not able to be resolved by corticosteroid or immune suppressive agents. Therefore, plasma exchange may be considered as a very significant form of treatment of pemphigus vulgaris. PMID- 2214243 TI - [The study on the specific eruptions of malignant lymphoma. II. Clinical and pathological interesting points, electron microscopic study, immune state and treatment]. AB - We investigated 31 cases of cutaneous malignant lymphoma diagnosed by skin biopsy during about 11 years at the University of Tsukuba hospital. The interesting points are the followings; the difference of cell morphology between the primary lesion and the secondary skin lesion was found in one case diagnosed of Lennert's lymphoma. The erythrophagocytosis of tumor cells was found at the relapse of one case of TCL. Eosinophils were increased in number in accordance with the severity in a case of MF. The electron microscopic study revealed the LC approaching to the tumor cells in ATL and MF, and TRS in ATL. Group A maintained better immunity of PPD and DNCB skin test than Group B. Non-specific eruptions in Group A were found frequently at the late stage, about half of which were cutaneous/mucous fungous infection. In the treatment of Group A, soft X-ray therapy was an excellent method at the point of the responsiveness, the painlessness, the interval of relapse and side effects. PMID- 2214244 TI - [Nutritional condition of epidermolysis bullosa patients assessed from body height and weight]. AB - Exact body height and weight data of patient with epidermolysis bullosa simplex (EBS) and recessive dystrophic epidermolysis bullosa (RDEB) were collected through a nation-wide epidemiologic investigation concerning epidermolysis bullosa (EB) patients. This data was then compared with the averaged body height and weight of age and sex matched normal controls. The nutritional condition of the EB patients was evaluated statistically. The data showed that height of female EBS patients was less than the controls (p less than 0.01), and furthermore, that height and weight of male and female RDEB patients was also less than the controls (p less than 0.01). These results indicated that EB, especially RDEB patients, were in the poor nutritional condition, and that the adequate nutritional management might significantly influence the prognosis of these patients. PMID- 2214245 TI - Detection of specific proteins in the aqueous humor in primary open-angle glaucoma. AB - To elucidate the mechanism of increased intraocular pressure in primary open angle glaucoma (POAG), the protein profiles of aqueous humor obtained from POAG patients were compared with those of cataract patients as a control group. Aqueous humor proteins were analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and detected by the ultrasensitive silver staining technique. In 79% of the samples taken from POAG patients, protein bands of 140,000 or 160,000 daltons were stained, but none were stained from cataract patients. The presence of these protein bands revealed statistically significant differences between the two groups. Protein bands of 140,000 or 160,000 daltons were evenly visible at all ages in POAG patients, and the positivity of bands had no correlation with sex or initial intraocular pressure level. It is possible that the ultrastructural changes of the aqueous outflow pathway in POAG may be related to the changes in the aqueous protein, presence of 140,000 or 160,000 daltons protein bands. PMID- 2214246 TI - Detection of early visual field change in ocular hypertension using STATPAC. AB - Perimetric tests were performed on 32 ocular hypertensive eyes (17 patients) with the C-30-2 threshold program of the Humphrey Visual Field Analyzer. The global indices of 32 ocular hypertensive eyes were compared with those of 34 normal eyes (17 controls). None of the 34 normal eyes had visual field sensitivity loss. However, three out of 32 ocular hypertensive eyes, which is 0.4%, had visual field sensitivity loss. Of these three eyes, two eyes showed generalized depression (MD, P less than 5%) and one eye showed paracentral scotoma. PMID- 2214247 TI - Detection of glaucomatous visual field defect using a screening program of Humphrey Field Analyzer. AB - To evaluate its clinical efficacy, we report the results of Armaly central field screening test in comparison with those of central 30-2 threshold test of Humphrey Field Analyzer. In 83 cases of normotensives, ocular hypertensives, and glaucoma patients with open-angle or narrow-angle enrolled in this study, a total of 143 eyes were examined. Fifty-four out of 61 patients (88.5%) and 73 out of 81 eyes (90.1%) with visual field defects were detected by the Humphrey Field Analyzer screening test. Eight eyes out of 81(9.9%) with visual field defects detected by the screening test were confirmed as false positive. All points of false positive were solitary, which tended to occur more frequently on superior visual field. A false negative of eight eyes out of 62 (12.9%) detected by the screening test was confirmed by the threshold test, which was more frequent on superior field and shown to be located more peripherally from the fixation point. There was no significant difference in either central sensitivity or age of the false positive and negative. PMID- 2214248 TI - Intraocular pressure and axial length in children. AB - The intraocular pressure and the anteroposterior length of the eye are of great clinical importance for the diagnosis and management, before and after surgery, of congenital glaucoma. It is well-known that normal intraocular pressure in children is different from the normal levels in adults. We performed measurements of intraocular pressure and axial length in 141 children who had been admitted for eye problems other than glaucoma. The intraocular pressures were measured with the Perkins hand-held applanation tonometer at the beginning of general anesthesia. Simultaneously, A-scan ultra-sound measurements of the axial lengths of the eyes were made. In 10 children under the age of two years, the intraocular pressure was 11.85 +/- 1.35 mmHg. In 79 children from two to seven years, the intraocular pressure was 12.80 +/- 1.73 mmHg. In 52 children from seven to 15 years, the intraocular pressure was 13.31 +/- 1.79 mmHg. The axial lengths of the eyes in children under the age of two years, from two to seven years, and from seven to 15 years, were 21.31 +/- 0.97 mm, 22.04 +/- 0.92 mm, and 23.22 +/- 1.00 mm, respectively. These results were considered to be guidelines for measuring intraocular pressure and axial length in children suspected of having congenital glaucoma. The differences of intraocular pressures stated by other authors are due to early measurement of the intraocular pressure at the beginning of general anesthesia. PMID- 2214249 TI - Non-contact tonometry: an ideal method for mass screening. AB - We evaluated one of the new non-contact tonometers, the Pulsair non-contact tonometer, to assess its accuracy and reliability. Measurements on 101 eyes were used to assess its accuracy against Goldmann tonometry measurements, and another 24 eyes were used to assess its reliability (reproducibility). The results showed the instrument to be highly accurate and reliable in measurement. PMID- 2214250 TI - Lysis of vitreous strands with neodymium: YAG laser. AB - Eighteen eyes with vitreous strands adherent to the corneoscleral wounds of previous cataract surgery were treated with neodymium: YAG laser to lyse those strands. Twelve eyes were treated for management of cystoid macular edema (CME group); six eyes were treated for prophylaxis of possible CME (prophylactic group). In the CME group, visual acuity improved two or more lines in nine eyes (75.0%), and seven eyes had a post laser visual acuity of 0.5 or better (One eye had a pre-treatment visual acuity of 0.5 or better). In the prophylactic group, visual acuity was either maintained at the pre-treatment visual acuity of 0.5 or better. In the prophylactic group, visual acuity was either maintained at the pre treatment level or improved in five eyes (83.3%) 18 months later following laser treatment. This procedure was complicated by retinal detachment in one case and the elevation of intraocular pressure over 10 mmHg in another case. PMID- 2214251 TI - Oscillatory potentials of local macular ERG in diabetic retinopathy. AB - The oscillatory potentials (OPs) in electroretinogram (ERG) have clinical values in measuring retinal functions of the early stage of diabetic retinopathy. However, OPs have, until now, been evaluated as components of total ERG recorded with a full field stimulus over the entire retina. Therefore, little information could be obtained about the macular condition (diabetic retinopathy). Using focal stimuli, we successfully recorded OPs in the human macular region. We modified our previously reported system for recording local macular ERG under the fundus monitor with an infrared television fundus camera. We evaluated macular OPs with simultaneously recorded a- and b-waves in many patients with diabetic retinopathy. In some kinds of early diabetic maculopathy, the macular OPs were selectively reduced, leaving the a- and b-waves intact. The macular OPs can be a valuable indicator in assessing the macular function in diabetic maculopathy. PMID- 2214252 TI - Early surgical management in bilateral acute retinal necrosis. AB - One patient with bilateral acute retinal necrosis underwent encircling scleral buckle, vitrectomy, and intravitreal acyclovir on both eyes. This procedure was performed on the right eye while the retina was attached. The retina of the right eye was reattached by performing fluid-gas exchange and modified panretinal photocoagulation when the retina subsequently detached. Soon after the development of retinal detachment in the left eye, the above surgical procedures were performed on the left eye, and the retina was successfully reattached. Bilateral acute retinal necrosis with significant vitreous opacification, which is a devastating ocular disease causing possible blindness in both eyes, requires more aggressive, early surgical management. PMID- 2214254 TI - Atherosclerosis and glomerulosclerosis in WHHL rabbits and obese Zucker rats. AB - The aorta and the kidney of 12 month old hyperlipidemic WHHL and obese Zucker rats, were examined morphologically. The WHHL developed severe and premature atherosclerosis but did not develop glomerulosclerosis. In contrast, the Zucker rats did not manifest atherosclerosis of the aorta, but developed glomerulosclerosis. These two animal models could be useful in understanding the roles of heterogeneous lipoprotein particles, genetic susceptibility, hemodynamic stress, and mesangial interactions with lipoproteins in the development of glomerulosclerosis. PMID- 2214253 TI - Topical fibronectin treatment in persistent corneal epithelial defects and corneal ulcers. AB - Topical fibronectin, autologous and homologous, was used to treat nine patients (eleven eyes) with persistent corneal epithelial defects and corneal ulcers that failed to improve with standard therapy. The fibronectin was purified from autologous and homologous plasma by gelatin-Sepharose 4B affinity chromatography and administered topically, 500 micrograms/ml five times a day, for three weeks. Complete or nearly complete reepithelialization was achieved in all patients regardless of the source of fibronectin, autologous or homologous. But healing times varied. The average healing time was 41.7 +/- 14.7 days (35.7 +/- 12.4 days for autologous, 50.8 +/- 14.4 days for homologous). Ocular symptoms were relieved significantly, and no side effects were observed. Over an average follow-up period of 5.2 months, no recurrences were noted. The results showed that homologous, as well as autologous, fibronectin was effective in patients with persistent corneal epithelial defects and corneal ulcers. PMID- 2214255 TI - Studies on the chironomid midges (Diptera, Chironomidae) of the Nansei Islands, southern Japan. AB - The Nansei Islands are located in the subtropical zone of the western Pacific Ocean between Kyushu and Taiwan, and are composed of the two main island groups, the Amami and the Ryukyu Archipelagoes. This area has been known for the presence of a number of indigenous animal species. Prior to the present studies, collections of the chironomids mainly in the urban areas of the three main islands of the Ryukyus were carried out by Sasa and Hasegawa, and a total of 42 species, including 25 new species, were recorded. Additional collections of the chironomids mainly in the mountainous areas of this region were carried out by the present author during 1988 and 1989, and a total of 26 species (including 12 new species) were recorded from Amami Island, and a total of 27 species (including 10 new species) were recorded from the Ryukyu Islands. Eight species among them, including 3 new species, were common to the two archipelagos. PMID- 2214256 TI - Synergy of OK-432 and recombinant interleukin 2 in the antitumor immunity induction and the cytotoxic T-lymphocyte generation. PMID- 2214257 TI - Synthesis of hepatitis B virus core antigen polypeptide in E. coli using pKK223-3 plasmid, a vector for expression, with tac promoter. AB - A hybrid plasmid was constructed by insertion of the HBc gene encoding HBcAg into the pKK223-3 plasmid at the SmaI cleavage site in the correct direction just downstream from the tac promoter and upstream from the rrnB terminator. The recombinant plasmid carrying the HBc gene was introduced into E. coli and cloned. HBcAg was synthesized in E. coli by using the expression plasmid under the regulation of the tac promoter and rrnB terminator. The tac promoter, derived from sequences of trp and lac UV5 promoters, has identical sequences in two domains (-35 and -10 regions) with optimal distance, and the Shine-Dalgarno sequence, which enables protein synthesis to start at the ATG of the adjacent HBc gene. The nucleotide sequence of the HBc gene and its predicted amino acid sequence were almost identical to those previously reported. Purified HBcAg has a molecular weight of 21,500. This polypeptide gave a positive reaction with anti HBcAg and anti-HBe antibodies, and was assembled into spherical particles 37 nm in diameter. The recombinant plasmid, carrying the HBc gene between the tac promoter (trp-lac hybrid promoter) and the rrnB terminator in expression plasmid pKK223-3, was useful for efficient expression of the HBc gene and production of HBcAg particles in E. coli. PMID- 2214258 TI - [Study on the usefulness of haptoglobin used on endoscopic injection sclerotherapy]. AB - The effect of haptoglobin (Hp) used on endoscopic injection sclerotherapy (EIS) was evaluated by examining the increase of serum free hemoglobin (FHb) and the changes of renal function. In control group, the increase of serum FHb (delta FHb) was paralleled with the volume of 5% ethanolamine Oleate (EO) injected intravariceally, and free Hp (FHp) was disappered in this group soon after EIS. On the contrary, in the group treated with Hp, neither the increase of FHb nor decrease of FHp were recognized. The significant increase of urine beta 2 microglobulin and NAG was recognized in control group. Therefore, if Hp is used at initial EIS, it would be prevented that serum FHb due to intravascular hemolysis increases, consequently the possibility of renal dysfunction. PMID- 2214259 TI - [Relation between localization of gastric mucosal lesions and microvascular disturbance]. AB - Acute gastric mucosal lesions in the rats were produced by intermittent electrical stimuli to a main trunk of the left gastric artery (LGA), right gastroepiploic artery (RGEA) or a posterior branch of the left gastric artery (PLGA). The image processing analysis was applied to determine the relation between distribution of the lesions and perfusion area of the supplying artery to which electrical stimuli were given. Electrical stimuli of 50 Hz, 5 msec, 100 microA was supplied to the artery for 30 sc three times with 10 sec interval. A series of these stimuli was repeated three times. The mucosal blood flow measured with the laser doppler method in each perfusion area was reduced to less than 35% of the control value during the electrical stimuli for 30 sec. After the repeated electrical stimuli to LGA, 85.8 and 95.4% of the mucosal lesions were found in the mean and maximum perfusion area of LGA, respectively. Electrical stimuli to PLGA caused 84.5% and 95.3 of the lesions in the mean and maximum area of PLGA, respectively. Stimuli to RGEA caused 53.4% and 74.1% of the lesions in the mean and maximum perfusion area of RGEA. In the antrum, electrical stimuli to LGA, PLGA or RGEA produced 0%, 5.4% or 5.0% of the mucosal lesions. It is concluded that the corpus mucosal lesions induced by regional ischemia are distributed in the ischemic area. PMID- 2214260 TI - [Effect of endothelin on gastric mucosal lesion in rats]. AB - Gastric mucosal blood flow and gastric mucosal prostaglandin E2 (PGE2) and prostacyclin (PGI2) were investigated in male Wistar rats intraarterially injected with endothelin (ET), an endothelium-derived vasoconstrictor peptide. Immediately following ET (4 nmol/kg) administration, gastric mucosal blood flow decreased. Then 30 min later, the blood flow reached the minimum, but PGE2 and PGI2 showed the highest value. PGE2 showed a tendency to decrease 90 min later, while PGI2 continued to show high value. There were redness and hemorrhagic damage in the gastric mucosa. Endogenous PGs were presumed to be relate to the regulation of the development of the mucosal damage owing to decrease in the blood flow after ET administration. PMID- 2214261 TI - [Effect of the lateral hypothalamic area-lesions on the development of gastric mucosal damages by water immersion restraint stress in rats]. AB - The role of the lateral hypothalamic area (LHA) in the development of gastric mucosal damages induced by water immersion restraint stress was evaluated in bilateral LHA-lesioned rats. The ulcer index of lesions (M +/- SEM, mm) was significantly higher in LHA-lesioned rats (21.6 +/- 2.8) than in both thalamus lesioned rats (9.8 +/- 2.0) and non-treated rats (10.2 +/- 1.5). The gastric acid and pepsin outputs during water immersion for 5 hours were significantly lower in the LHA-lesioned rats than in both the control rats. In the LHA-lesioned rats, PAS-positive mucus content of gastric corpus without lesions was significantly decreased after water immersion restraint stress for 5 hours. All these results suggest that lateral hypothalamic area plays an important role in the process of stress ulcer formation mainly through the disturbance of mucosal defensive mechanism such as changes in gastric mucus contents. PMID- 2214262 TI - [Effects of dopamine on stress ulcer]. AB - Preventive effect of dopamine on stress ulcer formation was investigated in rats. Dopamine 1-10 micrograms/kg/min suppressed the elevation of ulcer index significantly after water immersion and restraint stress in a dose-dependent fashion, however ulcer indices of 25 micrograms/kg/min of dopamine were higher than 10 micrograms/kg/min. Dopamine 1-10 micrograms/kg/min suppressed the decrease of gastric mucosal blood flow, gastric mucosal prostaglandin E2 content and gastric transmucosal potential difference during stress loading in a dose dependent manner, although the suppression of them in 25 micrograms/kg/min of dopamine was smaller than in 10 micrograms/kg/min also. Dopamine suppressed the increase of gastric acid secretion and gastric motility during stress loading in a dose-dependent fashion up to 25 micrograms/kg/min. These results indicates that dopamine suppresses the formation of stress ulcer by increasing defensive factors and decreasing aggressive factors. PMID- 2214263 TI - [Clinical and epidemiological study on factors of serious development of viral hepatitis type A]. AB - In order to investigate the factors that make viral hepatitis type A serious, clinical pictures were analyzed in 269 patients with viral hepatitis type A broken out during the past 8 years. In 1986 incidence of patients with severe hepatic dysfunction was higher and the average age of them was as high as 36.8 +/ 12.8 years old. The percentage of patients over 40 years of age was increasing from 1979 to 1986. Moreover in 6 patients with fulminant hepatitis type A, 4 of them (66.7%) were older than 50 years. Analysis of the clinical courses of 9 patients associated with underlying chronic liver disease disclosed serious hepatic dysfunctions in 7 out of 9. And the prolonged course of abnormal transaminase levels was observed in one of them. Therefore, aging and underlying chronic liver disease were considered as main factors that make viral hepatitis type A severe. PMID- 2214264 TI - [Studies on metabolic characteristics of cirrhotic rat hepatocytes using primary culture]. AB - To assess the metabolic characteristics of cirrhotic hepatocytes, a primary culture of hepatocytes was established using rat liver induced cirrhosis by CCl4 administration. Using this system, cell responsiveness to different metabolic and excretory stimuli was investigated and compared with a primary culture of normal healthy rat hepatocytes. Cirrhotic hepatocytes showed reduced protein synthesis in response to insulin and reduced urea synthesis in response to glucagon. However, DNA synthesis stimulated by insulin and EGF was significantly enhanced in cirrhotic hepatocytes. No significant difference was observed in the fluorescein diacetate excretion rate. Cirrhotic hepatocytes showed impairment of antipyrine metabolism and conjugation and excretion of unconjugated bilirubin. These results suggest indirectly that cirrhotic hepatocytes may be less functionally mature than normal healthy hepatocytes. PMID- 2214265 TI - [Eosinophilia in primary biliary cirrhosis]. AB - The numbers and the percent of eosinophils in peripheral blood of thirty patients with primary biliary cirrhosis were serially measured and were compared with their clinical data. eosinophils of 22 patients at non icteric stage (total bilirubin less than 2.0 mg/dl) were significantly higher (P less than 0.05) than those of 8 patients at icteric stage (total bilirubin more than 2.0 mg/dl). Seven patients (23.3%) showed eosinophilia with value of 6% or more and in which four patients (13.3%) showed eosinophilia more than 8%. These eosinophilia was found in non icteric patients alone but not in icteric. In two patients who have shown eosinophilia at their non icteric stage, numbers of their eosinophils decreased gradually following the increment of their total bilirubin levels. These results would indicate that eosinophils in the peripheral bloods of PBC patients could reflect some clinical conditions at their non icteric stage. PMID- 2214266 TI - [Hepatic and systemic hemodynamics in compensated cirrhosis--effect of posture change]. AB - The effect of changes in body posture on estimated hepatic blood flow (EHBF) and various hemodynamic parameters was examined in 15 patients with compensated cirrhosis. EHBF and various hemodynamic parameters were first measured with the patients in the supine position, and then again 10 min after tilting to 45 degrees. EHBF was 1089 +/- 315 ml/min at supine and 1065 +/- 328 after tilting; the difference was not significant. However, the patients were then divided into two groups according to the magnitude of the decrease in EHBF after tilting, with those showing a decrease of 10% of more assigned to group B, and those showing a decrease of less than 10% assigned to group A. It was found that ICG (R15) and BSP (R45) were significantly higher in group A. Meanwhile, among hepatic and systemic hemodynamics, wedged hepatic venous pressure, hepatic venous pressure gradient, free hepatic venous pressure, cardiac index, systolic blood pressure, systemic vascular resistance, and stroke volume were found to have changed significantly after tilting. These results suggest that posture change has no effect on EHBF in compensated cirrhotic patients. PMID- 2214267 TI - [Metabolism of sulfobromophthalein in jaundiced rat]. AB - We observed previously in humans that loading with BSP in obstructive jaundice resulted in elevated blood levels, of cysteine-conjugated BSP (Cyst-BSP). In order to clarify the mechanism of this phenomenon, an investigation was made into the origin of Cyst-BSP in rats with experimentally produced obstruction of bile duct (O-J). Using untreated rats as controls, the animals were determined for glutathione content and glutathione S transferase activity (GST) in liver cytosol. The influence of nephrectomy upon and the role of liver cell membrane in biodisposition of BSP were also investigated. The results are summarized as follows: 1) In the O-J group, the excretion in bile of glutathione-conjugated BSP (GSH-BSP) was markedly decreased. 2) O-J livers were found to have higher glutathione content and GST activity as compared to control livers. 3) Nephrectomy in O-J rats was followed by no gross change in the proportion of Cyst BSP in blood and liver cytosol. 4) Following administration of individual liver cell membrane components change from GSH-BSP to Cyst-BSP was noted to occur only in O-J rats. These results led us to surmise that GSH-BSP accumulated in the liver in O-J is hydrolyzed to Cyst-BSP in the liver cell membrane. PMID- 2214268 TI - [Effect of continuous arterial infusion of protease inhibitor on experimental acute pancreatitis induced by closed duodenal loop obstruction]. AB - The effectiveness of continuous arterial infusion of protease inhibitor on acute experimental pancreatitis was investigated. Acute hemorrhagic pancreatitis was induced by closed duodenal loop obstruction using mongrel dogs. The obstruction was released at 16 hr, and dogs were divided into three groups; Group I: non treated control, Group II: nafamostat mesilate (FUT-175) was admitted intravenously (5 micrograms/kg/min), Group III: FUT-175 was admitted via celiac artery. At 24 hr, the concentration of FUT-175 in the pancreatic tissues in group II and III were 905 and 4453 ng/g, respectively. The trypsin like activities in the pancreatic tissues in group I, II and III were 2.1, 1.4 and 0.7 nmol/min/mg protein, and the extent of necrosis of pancreatic parenchyma in each group were 49.5, 25.6 and 12.4%, respectively. Serum calcium, amylase and lipase levels were significantly improved in group III. These results suggest that continuous arterial infusion of protease inhibitor markedly decreases the extent of pancreatic necrosis in severe acute pancreatitis. PMID- 2214269 TI - [Three cases of esophageal or upper gastric varices due to invasion of malignant tumor to the portal vein]. PMID- 2214270 TI - [A case of Vasculo-Behcet syndrome with portal vein occlusion]. PMID- 2214271 TI - [A case of lupus peritonitis diagnosed by the immunological findings in the peritoneal fluid]. PMID- 2214272 TI - [Histopathological analysis of 73 autopsy cases of "acute-on-chronic" in Japan- influence of alcohol abuse on exacerbation of chronic liver disease]. AB - Cases of acute exacerbation in chronic liver disease ("acute-on-chronic") in Japan were surveyed by questionnaire method since 1986 and 220 cases were collected. 73 pathological specimens of 102 cases which were autopsied were subjected to morphological analysis. The cases were divided according to causes of acute exacerbations: namely super-imposed viral infection or drugs (Group I), unknown causes or post immunosuppressant therapy (Group II), alcohol abuse (Group III), operation, digestive tract hemorrhage or post TAE etc, (Group IV). Area of hepatic necrosis was large and regeneration of hepatocytes were significantly strong in Group I and II compared with cases of Group IV. Regeneration was also inhibited in liver of habitual alcohol drinker. Significant difference was shown in cases of Group IV. Pathologically liver of 10 cases of Group III divided to florried cirrhosis (3 cases), alcoholic liver cirrhosis (4 cases) and alcoholic hepatitis combined with post hepatitic liver cirrhosis (3 cases, all HBV carriers). PMID- 2214273 TI - [Studies on binding sites of epidermal growth factor in rat gastric mucosa]. PMID- 2214274 TI - [The significance of measurement of serum sialic acid in patients with Crohn's disease]. PMID- 2214275 TI - [Degeneration of interfoveolar cells of the rat gastric mucosa by 16,16-dimethyl prostaglandin E2]. PMID- 2214276 TI - [Study of acute gastric mucosal lesion induced by endotoxemia]. AB - Acute gastric mucosal lesion (AGML) was induced six hours after the administration of endotoxin. The decrease of gastric mucosal blood flow, used to be supposed as an important factor of the formation of AGML, was not found, but thiobarbituric acid (TBA) reactants in the gastric mucosa were increased three hours after endotoxin injection, 198 +/- 18.2 (vs control 130 +/- 18.2). The administration of platelet activating factor (PAF) inhibitor, CV3988, reduced the formation of AGML and increase of the TBA reactants. These results suggested that the chemical mediator like PAF and free radicals may play an important role in the pathogenesis of gastric mucosal injury induced by endotoxemia, without the decrease of mucosal blood flow. PMID- 2214277 TI - [A study on the new measurement of gastric lesions with an electronic endoscope]. AB - We carried out measurement of gastric lesions in the inner surface of the stomach with a measuring system, which is composed of a stereo endoscope and a personal computer. Basically, the length on a flat board from 10 mm to 50 mm was measured by varying the distance between the lens and the board and the angles of the endoscope at first. The error of the measurement was less than 8.5%. Secondly, ten physicians of our clinic attempted the measurement of the pasted discs on the inner wall of a stomach model with the endoscope. The average measurement error and the average time required for endoscopy became more better using the newly developed system than a measuring rod. Clinically, we measured the length of stomach lesion and of normal mucosa in six patients and compared the values obtained with those of resected fresh specimens. The length of stomach lesions could be measured more accurately than that of normal mucosa of stomach. From our observations, it can be said that this system is as available as the basic examination procedures in use at present and worth using in clinical procedure for it's high reliability. PMID- 2214278 TI - [A study on endoscopic hemostasis from the viewpoint of morphologic traits of Dieulafoy ulcer--an attempt at endoscopic hemostasis by local injection of aethoxysklerol and ethanol]. AB - Characteristics of the vascular course of ruptured vessels in the submucosal layer of Dieulafoy ulcer were studied, and endoscopic hemostatic treatment was performed using Aethoxysklerol and ethanol. 1) Observations of vessel courses in serial sections revealed that ruptured vessels in Dieulafoy ulcer exhibit rhexis in the lateral portions of the vessel and long courses over the ulcer margin in the submucous layer. 2) More dependable hemostasis seemed to be provided by thrombosis not only at the source of bleeding. i.e., at the site of vessel rupture, but also in the region of the whole ruptured vessel in the submucous layer. 3) Hemostatic treatment by local injection of Aethoxysklerol and ethanol was performed in 4 patients with Dieulafoy ulcer, and complete hemostasis was achieved in all 4 patients. PMID- 2214279 TI - [Evaluation of intrahepatic distribution of inferior mesenteric blood flow by transrectally administered 123I-IMP]. AB - Intrahepatic distribution of the inferior mesenteric blood flow was evaluated with scintigraphy with transrectally administered 123I-iodoamphetamine (IMP). Twelve patients without liver diseases were studied. The IMP image was divided into 3 types; bilateral, left lobar predominant and right lobar predominant. Bilateral, left lobar predominant and right lobar predominant types were observed in 5, 5 and 2 patients respectively. Furthermore, uneven distribution pattern in the left or right lobe was observed in 2 of 5 patients with bilateral lobar type, 4 of 5 patients with left lobar predominant type and 1 of 2 patients with right lobar predominant type. In one patient with left lobar predominant type, repeat examination demonstrated bilateral lobar type. These results suggest that intrahepatic distribution of the inferior mesenteric blood flow is not uniform and consistent. PMID- 2214280 TI - [Clinical investigation of 10 patient with amebic dysentery]. AB - Data were obtained in 10 patients with amebic dysentery at Osaka Socio-Medical Center hospital during the period from April 1985, to April 1989. All of the patients were male, and their average age was 41 years old. In the past history, all of them had never gone to foreign country, and 7 patients had the habit of homosexual love. In the serological test, positive rate of antiamebic antibody was 100% (6/6) by agar gel diffusion, that of antibody of Toreponema pallidum was 60% (6/10) by TPHA, but anti AIDS antibody was not detected (0/3) by HIV. Detectability of Entoamoeba hystolitica was 70% (7/10) in stool, 50% (2/4) in liver abscess, 25% (1/4) in biopsied specimens of rectal mucosa. Then, we fund that the serological test for antiamebic antigen was useful for diagnosis of this disease, and suspected that homosexual contact contributed to the infection of E. hystolitica. PMID- 2214281 TI - [Immunohistochemical study on epidermal growth factor and its receptor in human pancreatic carcinoma]. AB - We investigated immunohistochemical expressions of the epidermal growth factor (EGF) and the epidermal growth factor receptor (EGFR) in 25 cases of pancreatic carcinoma, including 13 cases of metastatic lymph nodes. EGF and EGFR were stained mainly in the cytoplasm and on the surface of some pancreatic carcinoma cells, with positive rates of 18/25 (72%) and 9/25 (36%) respectively. In all cases EGFR was noted only when EGF was also detected. EGF and EGFR were stained frequently in differentiated types. In metastatic lymph nodes, EGF and EGFR were found in 54% and 15% respectively, and they were detected only when they were also noted in the same patient's primary lesions. EGF and EGFR were found more frequently in Stages III and IV than in Stage II. These results emphasize that EGF and EGFR may promote both the proliferation and the differentiation of human pancreatic carcinoma cells, as in other sites. PMID- 2214282 TI - [A heterotopic Brunner's adenoma in the stomach: a case report]. PMID- 2214283 TI - [A case of malignant lymphoma with multiple lymphomatous polyposis of the colon associated with chylothorax and chylous ascites]. PMID- 2214284 TI - [A case of liver cirrhosis with vesical and mesenteric varices who complained gross hematuria]. PMID- 2214285 TI - [Primary sclerosing cholangitis mimicking bile duct carcinoma at porta hepatis. A case report and review of Japanese literature with special reference to the feature of associated jaundice]. PMID- 2214287 TI - [Examination of distribution of Helicobacter pylori on gastric mucosa using dye endoscopy]. PMID- 2214286 TI - [A case of double choledochus with ectopic drainage into the body of the stomach]. PMID- 2214288 TI - [Estimation of portosystemic shunt index in superior mesenteric vein by duodenal administration of 123I-IMP]. PMID- 2214289 TI - [32nd meeting of the Japanese Society of Gastroenterology. Nara City, 25-27 October 1990. Abstracts]. PMID- 2214290 TI - [Effect of S-adenosylmethionine on methylation of inorganic arsenic]. AB - We studied the role of S-adenosylmethionine (SAM) as a methyl group donor in the methylation of inorganic arsenic in mammalians. The SAM and S adenosylhomocysteine (SAH) levels in the livers of untreated hamsters were 74.3 +/- 8.2 and 40.0 +/- 6.4 nmol/g, respectively. The SAM level was 63.9 +/- 6.5 nmol/g following oral administration of 1.5 mg/kg of arsenic trioxide, which was 14% lower than the control level (t-test, p less than 0.05). This fall of the SAM level in the liver presumably derived from the SAM having acted as a methyl group donor. Oral administration of 1.5 mg/kg of arsenic trioxide once only to hamsters pretreated intraperitoneally with 2.0 mg/kg of SAM once only gave the following arsenic levels in the liver and urine. The dimethylated arsenic (DMA) levels in the livers of hamsters treated with SAM plus arsenic trioxide were significantly high, that is, 2 times as high as the control value at 6 hours, and 1.5 times as high as the control value at 24 hours after the administration of arsenic trioxide. The urinary DMA excretion rate was significantly higher, that is, higher by 36%, than the control value. The urinary DMA excretion rate following pretreatment with SAM was not dose-dependent. Pretreatment with methionine failed to exert any significant acceleratory effect on the methylation of arsenic trioxide. The decreasing pattern of the SAM level in the liver following administration of arsenic trioxide and the DMA behavior in the liver and urine following administration of SAM and arsenic trioxide revealed that SAM accelerated the methylation of inorganic arsenic. In other words, it appeared that SAM could be a very potent methyl group donor to inorganic arsenic. PMID- 2214291 TI - [Fatigue and performance of divers during a simulated, non-saturated oxygen helium dive to 180 meters]. AB - A non-saturated mixed-gas dive to 180 meters depth was carried out at JAMSTEC, using diving simulator (hyperbaric chamber) facilities. Compression started at 10:00 h with helium and oxygen and was carried out at a rate of 12 m/min. Decompression started at 11:15 h using the Comex Helox 180 Diving Manual. Decompression to 1 ATA required 49.2 h. A survey of subjective symptoms, sleep feelings and ball-bearing tests were performed. All night electrophysiological recording of subjects' sleep was performed and polygraphic analysis of nocturnal sleep was done with visual scoring. The results were as follows: Arriving at 180 meters, the complaint rate was 39.2% and fatigue was greater. The type of fatigue that was based on the composition + ratio of symptoms was that of mental fatigue. During the decompression it was recovery. The performance in the ball-bearing test decreased about 20% at a depth of 180 meters because of tremors and disturbance of attention as well as other factors showing symptoms of high pressure nervous syndrome. The sleep feelings were different in experienced persons and non-experienced persons. The non-experienced persons had markedly decreased REM stages and slept badly all night. Based on these results, fatigue and the performance of divers were discussed. PMID- 2214292 TI - [Ion chromatographic determination of inorganic anions in human serum]. AB - The ion chromatographic method is a rapid and reliable technique for the simultaneous determination of inorganic anion concentrations in serum. We are investigating the effects of various diseases on the serum levels of the following inorganic anions: phosphate, bromide, nitrate, and sulphate. In this paper, we tested the intra- and intermeasurement reproducibility of the ion chromatographic method using pooled normal human serum. We found a good intrameasurement reproducibility for all of the above inorganic anions. The intermeasurement reproducibility was good for three of the inorganic anions but not for nitrate. We measured the serum levels of these inorganic anions in 241 inhabitants in one rural area. Using sera of normal inhabitants chosen from the above group, we used the mean value plus or minus two standard deviations as the normal range of each inorganic anion. Our values are in agreement with previously published reports. We found that the serum levels of nitrate and sulphate tended to be increased in inhabitants with liver or kidney disfunction respectively. PMID- 2214293 TI - Study on digestibility and energy availability of daily food intake in Japanese (Part 3. Cereals). AB - Four male Japanese were fed a semisynthetic diet including egg and soy powder as protein source for seven days (Basal-diet period), and in the following seven days 200 g of polished rice, wheat flour and buckwheat flour added at the expense of part of the corn starch and sugar in the basal diets (Test-diet period). Urine and feces were collected throughout both periods and the contents of nitrogen, fat and energy in these excreta were determined. Digestibility of protein (N), fat and carbohydrate (by difference) was calculated. The protein digestibilities of the polished rice (in the form of cooked grains), wheat flour (in the form of cooked powder) and buckwheat flour were 89.6 +/- 5.0%, 93.4 +/- 2.9% and 85.1 +/- 2.5%, respectively. The fat digestibilities of the polished rice, wheat flour and buckwheat flour were 93.6 +/- 1.8%, 70.8 +/- 13.5% and 103.1 +/- 8.4%, respectively showing relatively large variation (This results may be caused by an errors in measurement). The carbohydrate digestibility was close to 100%. The net energy availabilities of the polished rice, wheat flour and buckwheat flour were 100.6 +/- 1.4%, 96.5 +/- 1.1% and 96.0 +/- 1.1%, respectively. PMID- 2214294 TI - [Evaluation of waist size as a health risk indicator for obesity]. AB - The purpose of this study is to evaluate waist size as an indicator of health risk among subjects considered to have normal body construction based on height weight obesity indices. For estimating standard waist sizes based on height, a regression equation was formulated from 46 male subjects who had no abnormal findings in their health checkups. The regression equation was as follows: Standard waist size (cm) = 0.8 X height (cm)-57.7. The ratio of measured waist size to standard waist size was defined as the "waist ratio". The correlation coefficient between the waist ratio and the modified Broca's obesity index was 0.898 (N = 207, p less than 0.01). To clarify the meaning of the waist ratio, 95 male subjects were divided into three groups on the basis of the difference between their waist ratio and their obesity index. The group whose waist ratios were larger than their obesity indices had significantly worse findings than the group whose waist ratios were not in the following medical categories: systolic blood pressure, glutamic oxaloacetic transaminase levels, gamma glutamyl transpeptidase levels, uric acid levels, total bilirubin, electrocardiogram readings and optic funduscopic observation. Accordingly, the waist ratio derived from waist size might be useful for assessing obesity-related health risks even for subjects judged to be normal from the height-weight obesity index. PMID- 2214295 TI - [Effect of zirconium on immunological reactions of T cells and macrophages in mice]. AB - The effects of zirconium (Zr) on T cells and macrophages in mice were studied in vitro using the indexes of immunological reactions, mitogenesis of C3H/HeJ mouse thymocytes induced by PHA and the production of interleukin-1 of C3H/He mouse intraperitoneal macrophages (MIL-1). The mitogenesis of thymocytes induced by PHA when stimulated with Zr solutions at various concentrations or culture supernatants of macrophages stimulated with LPS and Zr, or Zr alone, ware as shown below. 1. The mitogenesis of thymocytes by PHA was enhanced in the presence of Zr at 0.625-2.5 microM, and suppressed in the presence of Zr at 5-10 microM in culture 2. This reaction was enhanced by the addition of supernatants of macrophages stimulated with LPS and Zr. The most activation by LPS and Zr was shown at concentrations of 0.625-1.25 microM in culture, and the degree activated corresponding to 12.5-25 I.U. of MIL-1. 3. On the other hand, this reaction was inhibited by addition of supernatants of macrophages stimulated with Zr alone. From these results, it is suggested that Zr serves various functions such as an activator or inhibitor of T-cell mitogenesis by PHA, and that this may depend upon the Zr concentration in culture. In regard to the effect of Zr on MIL-1 production, Zr may activate this reaction by LPS, and Zr alone may induce MIL-1 production from macrophages. PMID- 2214297 TI - [Secular changes of the mean birth weight and the mean gestational day at an obstetric clinic in Naha]. AB - In our previous study we reported that the secular change of the mean birth weight (MBW) of Okinawa was different from that of Japan as a whole, that is, the MBW of Okinawa was lower, but the annual increase rate of the MBW of Okinawa was larger than that of Japan as a whole. Through analyses using birth records of several obstetric facilities in Naha, we concluded that this phenomenon must be due to the remarkable improvement of the socioeconomical environment of Okinawa. In this report we analyzed secular changes of mean birth weight (MBW) and mean gestational day (MGD) of 15,847 singleton babies born at an obstetric clinic in the city of Naha for the 33 years from 1955 to 1987. To avoid fluctuations of annual changes in MBW and MGD caused by a small number of babies born in a single year, we also used the moving average of three years. In analyzing birth weight we stratified birth weight by sex, parity and the number of gestational weeks. It is considered that birth weight stratified by the number of gestational weeks reflects the intrauterine growth rate of infants. According to our results, both the MBW of infants with 40 gestational weeks, which reflects the intrauterine growth rate, and the MGD increased during the period from the 1950s to the early 1970s in this clinic. On the basis of these results we concluded that the increase of birth weight in this clinic until the early 1970s was due to increases in both the intrauterine growth rate and the gestational period. Our results also show that the mean height of mothers who delivered at this clinic also increased, which might reflect the development of the socioeconomical environment during their childhood. During the period when MBW increased, the economic growth rate of Okinawa was higher than that of other prefectures. From these results we concluded that the MBW can be used as a community health indicator reflecting the total health condition in a given community. PMID- 2214296 TI - [Factors contributing to the difference of hair mercury concentrations between the sexes]. AB - Scalp hair samples were collected by mail from 97 married couples who were living in several places in Okinawa-prefecture and supposedly had no specific exposure to mercury compounds. They were selectively analysed for organic and inorganic mercury content and the difference of hair mercury concentration between the sexes was discussed in relation to the frequency of fish intake, fish species, drinking habits and permanent-wave hair treatment. Results obtained were as follows: 1) The increase in hair levels of organic and inorganic mercury concentrations was roughly proportional to the dietary intake of fish in the range from none or low to moderate frequencies for both husbands and wives. However, this increase was not proportional to the dietary intake of fish in the range from moderate to high frequencies, showing almost the same level irrespective of the frequency of fish intake. 2) Though husbands and wives had dietary consumption patterns quite similar to each other, husbands were found to have higher hair organic mercury levels than wives, the average values being 6.40 ppm with a standard deviation of 4.69 ppm for husbands and 2.86 ppm with a standard deviation of 1.97 ppm for wives, respectively. The difference was statistically significant. No significant difference between the sexes was detected for inorganic mercury concentrations. However, a highly significant positive correlation coefficient for organic mercury and also a significant positive correlation coefficient for inorganic mercury were found between husbands and wives. 3) Hair without permanent-wave treatment showed higher levels of organic mercury concentrations than hair with permanent-wave treatment for both husbands and wives. Drinkers also had higher levels of hair mercury as compared to non-drinkers. However, the lower levels of organic mercury concentrations in women's hair than in men's hair were not fully explained by these factors. 4) Both men and women who showed higher hair levels of organic mercury had a preference for highly predatory fish such as tuna and bonito, which probably contributed most to the human intake of mercury. PMID- 2214298 TI - [Difference of iron stores represented in bimodal distribution of erythrocyte values among a healthy male group]. AB - The distributions of erythrocyte values (red cell count, hemoglobin concentration, etc.) of healthy male workers working in a certain factory were studied in order to evaluate the usefulness of the variables as health indicators. In addition to the estimation of erythrocyte values, anamneses concerning chronic bleeding, smoking habit and alcohol consumption were questioned and serum Fe, Cu, TIBC, ferritin, plasma erythropoietin, and serum enzymes (GOT, GPT, gamma-GTP) were measured. Two-dimensional frequency distributions with axes for the red cell count and hemoglobin concentration, and frequency distributions of the score calculated from principal component analysis, showed bimodal patterns. Using nonlinear curve fitting methods, the distributions of principal component scores were fitted to a mixture of two different Gaussian distributions. The workers were then divided into two groups corresponding to the Gaussian distribution he belongs. Then the frequencies of the items and mean values of the variates were compared between them. There were no differences in the incidences of diseases that caused iron deficiencies, but the mean serum ferritin level was significantly lower in one group than in the other, in other words the workers belonging to the group with low serum ferritin level had smaller iron stores than the other. The mean serum erythropoietin level and the mean serum copper level were higher in that group than in the other. As a result, this analysis gives a new evaluation of the health status of a man who belongs to the so-called healthy male group. PMID- 2214299 TI - [Peripheral circulatory responses to sustained handgrip in workers using vibrating tools]. AB - In order to study the effects of static force such as a handgrip in detail, the peripheral circulatory function and the autonomic nervous function of workers who used chain-saws were examined in a handgrip test at 30% of maximum voluntary contraction (30% MVC). Workers using chain-saws were divided into three groups: group A without any symptoms, group B with numbness and/or pain but without Raynaud's phenomenon and group C with Raynaud's phenomenon. The results obtained were as follows: 1. The finger blood flow (FBF) of all groups significantly decreased during the handgrip and significantly increased after the end of the handgrip as compared with the initial value. There was a tendency for the FBF decrease of group C to be less than that of group A. 2. The mean value of both maximum FBF decrease and maximum FBF increase during handgrip tests fell in alphabetical order (A, B, C). The maximum FBF increase of group C was significantly less than that of group A. 3. The finger skin temperature (FST) of each group significantly fell during the handgrip but there was no significant difference among the three groups. FST returned to the level of the initial value one minute after the end of the handgrip, and significantly rose two minutes and three minutes after the end of the handgrip as compared with the initial value. 4. Both the systolic blood pressure and the diastolic blood pressure of all groups significantly rose during the handgrip but there was no significant difference among the three groups. Concerning the maximum rise of diastolic blood pressure, which is an indicator of autonomic nervous function, there was no significant difference among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214300 TI - [Relative weight and mortality during a five-year follow-up study in an aged population--a study of aged inhabitants of a rural area in Japan]. AB - The present study, a follow-up study for 669 aged examinees of a health check performed in July 1983 in a rural area in Fukushima Prefecture, was conducted to clarify the relationship between relative weight and mortality among aged individuals living in a Japanese rural area. Using the standard body weights calculated from Japanese mean body weights by sex, age class (60-69 and 70 or more) and height cited from the data of the Ministry of Health and Welfare from 1966, mortalities during the five year follow-up were compared among four groups different in relative weight at baseline. The results are as follows. 1) The mortalities in the group of 'Relative weight less than or equal to -10% the leanest group among the four groups, were highest in both sexes, 52.8 per 1000 person-years for males and 33.2 per 1000 person-years for females. On the other hand, those in the group of '+10% less than or equal to Relative weight less than +20%' were lowest in both sexes, 23. 1 per 1000 person-years for males and 7.0 per 1000 person-years for females. In females, the difference in the mortality between these two groups was statistically significant at the 0.05 level, provided age structures in both groups were taken into consideration. 2) In both sexes, the mortalities of cancer and cerebrovascular disease in the group of 'Relative weight less than or equal to -10%' were highest among the four groups, whereas such mortalities in the group of '+10% less than or equal to Relative weight less than +20%' were lowest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214302 TI - [On the life span and aging]. PMID- 2214301 TI - [Effects of methylmercury on ethanol-induced sleeping time of mice]. AB - This study was carried out to clarify the effects of methylmercury intoxication on the ethanol-induced sleeping time of mice. The mice were injected with methylmercury chloride (MMC) (10 mgMMC/kg body weight) subcutaneously for 1, 5 and 10 successive days (1, 5 and 10 inj.), and control mice received only saline. Twenty-four hours, after the last injection, these mice were treated with ethanol (4.5 mgEtOH/kg body weight) intraperitoneally and subsequent sleeping time was observed. After 24 hours, mice were sacrificed to measure the concentration of MMC in various brain regions and liver. A similar experiment with ethanol treatment was also performed to assay the biogenic monoamines in various brain regions and alcohol dehydrogenase (ADH) activity in liver. The results can be summarized as follows: 1) Ethanol-induced sleeping time was 170 min. in the 10 inj. and it was significantly longer than saline, 1 and 5 inj. However, other experimental groups showed no change when compared with saline. 2) Norepinephrine levels increased in white matter and pons + medulla after 1 inj. 3) Dopamine levels increased only in white matter of the 10 inj. when compared with saline. No changes were shown in the other groups. 4) Serotonin levels increased in all the regions after 1 inj. 5) ADH activity in liver did not show any alteration during the experimental period when compared with saline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214303 TI - [Neuronal death and neurotrophic factors in Alzheimer's disease]. AB - Progressive neuronal death in cerebral cortex and subcortical regions may lead to dementia in Alzheimer's disease (AD). The neuronal death is accompanied by accumulation of senile plaques, neurofibrillary tangles and curly fibers. Recent immunocytochemical studies have suggested that abnormal sprouting responses, occurring in AD brain, may be involved in the formation of these lesions. The hypothesis concerning the lack of neurotrophic factors cannot explain abnormal sprouting responses in AD brain. We have investigated the mechanism of abnormal sprouting responses in AD brain, using primary culture of rat cerebral cortical neurons. In AD brain, loss of growth-inhibitory factors led to an apparently higher level of neurotrophic activity. One of the growth-inhibitory factors in normal aged brain was a 5 kDa heat-stable acidic protein. These results suggest that loss of inhibitory factors may induce abnormal sprouting responses in AD brain. In consequence, neurons might be exhausted and die. PMID- 2214304 TI - [Studies of the location in the focus of dementia syndrome with PET and MRI]. PMID- 2214305 TI - [The diagnostic criteria of dementia and screening tests]. PMID- 2214306 TI - [Early diagnosis and prevention of dementia in the aged]. AB - From the view point of prevention and treatment of dementia, dementia can be classified into three main groups. The first is treatable or preventable dementia. Unfortunately, this group occupies only 10 or 20% of all demented patients. However, early diagnosis and treatment of diseases belonging to this group are particularly important. The other two groups are Alzheimer-type dementia (ATD) and vascular dementia. Early diagnosis of ATD is still rather difficult. We recently have found that alpha 1-antichymotrypsin (alpha 1-ACT) increases significantly in the serum and cerebrospinal fluid in ATD. Thus, alpha 1-ACT can be used as an antemortem biological marker of ATD. Positron emission CT (PET) is also useful for the early diagnosis of ATD, because decrease in CMRO2 in the unilateral temporo-parietal region occurs in a relatively early stage of this disease. On the other hand, vascular dementia can be said to be becoming one of the treatable or preventable dementias. Vascular dementia is mainly based on cerebral infarction. Therefore, prevention of initial stroke is most essential. For this purpose, correction of risk factors and use of antiplatelet agents in those cases suffering a transient ischemic attack or subjective symptoms are necessary. PMID- 2214307 TI - [Prevention and treatment of senile dementia]. PMID- 2214308 TI - [Support system for the demented elderly--the viewpoint of community care]. AB - Judging from the features of senile dementia, it is desirable for the demented elderly to receive care at their places to which they are accustomed and to be surrounded by affectionate families, if possible. Year by year, however, sufficient intrafamilial care is becoming more and more difficult because of increasing numbers of nuclear families, women's into society, the deteriorating housing situation and the like. Accordingly, the importance of community care is increasing; an integrated care system with close cooperation of medical facility services and at-home services needs to be established. Three important measures; i.e. home helper dispatching, short stay activity and day service activity as well as close cooperative work for health activities, medical care and welfare are still far from satisfactory, though these problems have begun to be tackled actively. Various types of advanced models and regional network systems exist fulfilling several necessary conditions for effective functioning. The need of a three-layer structure was emphasized based on a practical study of Matsubara City, Osaka. PMID- 2214309 TI - [The problems of care in elderly institutions]. PMID- 2214310 TI - [Care for dementia patients by their families and home care]. AB - Present problems concerning home care for the aged including the following three points: 1. The extent of the period during which care is needed has been prolonged as the aged live longer than in previous times. 2. The range of need for home care has increased. 3. As a result of the increase of the individual dependent "life support infrastructure" due to the decreased role of the family dependent "life support infrastructure", the aged, who were more self-supporting in past, have become more dependent on care both in quality and quantity. In particular, dementia patients gradually worsen, therefore care for them becomes increasing by difficult with time. This reports attempts to clarify the actual conditions of care for dementia patients by long term stay, short term stay and day care. At present it is difficult to ensure sufficient human terminal care. To overcome this problem, some families caring for dementia patients have formed "self-help groups" and give mutual support while attempting to approach to professional aid groups. While the family is the core of the home care system, it is not necessarily home care per se. Medical and nursing systems should improve home care by creating a system by which professionals are able to approach to families caring for dementia patients through two ways of "waiting" and "visiting" community programs, and by building closer connections with the welfare service. PMID- 2214311 TI - [Hemodynamic changes during dietary salt loading in elderly patients with essential hypertension]. AB - Hemodynamic changes with dietary salt loading were assessed by Doppler echocardiography during different sodium intake (7 g/day for 8 weeks, 20 g/day for 1 week) in 29 elderly patients with essential hypertension (81.6 +/- 6.7 years, 4 men, 25 women). With salt loading, 24 patients whose mean blood pressure (MBP) increased by 10% or more were defined as salt sensitive (SS) group, and 5 patients whose MBP did not change, or increased by less than 10% were defined as non-salt sensitive (NSS) group. Based on the mitral flow velocity integral, cardiac output (CO) was calculated, and total peripheral resistance (TPR) was calculated as MBP divided by CO. Nine of the 24 SS patients were termed "SS (COdep)" whose CO increased significantly with salt loading. In the remaining 15 SS patients termed "SS (TPRdep)", TPR increased significantly with sodium repletion. Blood flow in the common carotid, superior mesenteric, or terminal aorta was calculated from each flow velocity integral. The percent change in peripheral resistance calculated by dividing MBP by each blood flow was obtained. There were no significant percent changes in the common carotid resistance in SS (COdep), SS (TPRdep) or NSS groups. The superior mesenteric resistance increased significantly in all three groups. The terminal aortic resistance increased in the SS (TPRdep) group, but decreased in the SS (COdep) or NSS group. These results indicate that salt sensitivity is ascribable to changes in regional vascular resistances. PMID- 2214312 TI - [Effect of aging on bone mineral content. Part VII. The evaluation of osteoporosis treatment by the measurement of total body bone mineral content using dual photon absorptiometry]. AB - In order to evaluate the degree of accuracy of measurement of total body bone mineral content (TBBMC) by dual photon absorptiometry (DPA), the TBBMC in four healthy male volunteers were measured serially for 3 to 12 months. In three to six determinations of TBBMC in various stage of radiation source (153-Gd), the coefficients of variation in four subjects were 1.59, 0.74, 1.25 and 1.27%. Thus, the mean CV was 1.22 +/- 0.35% (mean +/- SD). This indicates that the measurement of TBBMC using DPA is an accurate tool for long-term follow up of bone mineral content and up to 1.6% change of TBBMC might be considered to be a significant change in TBBMC. No apparent drift of TBBMC associated with source decay was noticed in the present study. Subsequently, fifteen females with osteoporosis were studied to evaluate the efficacy of certain therapeutic modes. The patients were divided into two groups. Group 1 (n = 10) given 10 to 40 U of elcatonin (eel calcitonin derivative) intramuscularly every week for 3 to 6 months. Group 2 (n = 5) were treated with 0.5 mu/day of oral 1-alpha-OHD3 for 3 to 6 months. The TBBMC of these fifteen patients were followed by DPA (Lunar DP-4). Seven patients out of ten treated with elcatonin (70%) showed significant (up to 1.6% change in TBBMC compared with baseline) increase in TBBMC after 3 to 6 months treatment. The mean percentage change in TBBMC in group 1 was 101.9 +/- 2.7% (mean +/- SD) when the initial TBBMC was taken as 100%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214313 TI - [Monoclonal antibody analysis of glomerular, tubulo-interstitial infiltrating immune cells in various glomerulonephritis]. AB - To investigate the role of cell-mediated immunity (CMI) in glomerulonephritis (GN), we identified the infiltrating immune cells both within the glomerulus and in the interstitium. Frozen sections from 103 patients with various forms of GN: 10 with minor glomerular abnormality (MGA) as control, 10 with minimal change nephrotic syndrome (MCNS), 10 with membranous nephropathy (MN), 9 with focal glomerulosclerosis (FGS), 30 with IgA nephropathy (IgAN), 22 with acute post streptococcal glomerulonephritis (APSGN), and 2 with rapidly progressive glomerulonephritis (RPGN) were examined using monoclonal antibodies (MoAb) by indirect immunoalkaline-phosphatase labelling. In most glomerulonephritis, monocyte/M phi and helper/inducer T cells were predominantly infiltrating in the interstitium, but intraglomerular infiltration was rare, except for APSGN. This interstitial infiltration increased proportionally to the level of serum creatinine, and was most prominent in RPGN. Apparently different distribution was seen in APSGN, that is, prominent increase in total number of intra-glomerular monocyte/M phi infiltration with slightly increased T cells. The change was correlated with time after onset; namely the more leucocytic infiltration was observed when the tissue was taken earlier. These data suggest that in APSGN, monocyte/M phi accumulate in glomeruli via cell mediated immunity in addition to humoral immune mechanism resulting in glomerular hypercellularity, whereas in most chronic glomerulonephritis interstitial leucocyte infiltration, particularly helper T cells and monocyte/M phi may play an important role in the progression of glomerulonephritis. PMID- 2214314 TI - [Measurement of the charge on red blood cells in patients with various glomerulopathies]. AB - Red blood cells have a negative charge on their surface which prevents Rouloau formation. This charge may reflect the charge on glomerular capillaries. Using alcian blue, we measured the negative charge on red blood cells in patients with IgA nephropathy (IgAN), membranous nephropathy (MN), minimal change nephropathy (MCN) and focal glomerular sclerosis (FGS), for which the diagnosis was determined by renal biopsy. The alcian blue values for the normal control, IgAN, MCN (nephrotic phase), MCN (remission) and MN were 155.3 +/- 12.3, 140.9 +/- 23.9, 101.7 +/- 18.4, 152.9 +/- 11.2 and 140.9 +/- 23.6 ng per 1 x 10(6) red blood cells, respectively. The charge was more significantly decreased in MCN during nephrotic phase than other renal diseases and the normal control. The charge in MCN was within the normal range on remission. When we studied the correlation between the charge on red blood cells and proteinuria during steroid therapy, the charge in MCN was found to increase with reduction of proteinuria, while there was no change in MN and FGS with reduction of proteinuria, i.e. it was usually within normal range. The reduced charge was associated with the nephrotic phase in MCN. The difference in the charge on the red blood cells between MCN and FGS during nephrotic phase seems to suggest a different etiology of proteinuria. Measurement of the charge on red blood cells could be an useful method for differentiating MCN from other renal diseases in the nephrotic phase. PMID- 2214315 TI - [Correlations among the renal parenchymal components and renal function with IgA GN; age related changes]. AB - To clarify and evaluate the changes by aging to renal parenchyma of IgA nephropathy with normal renal function (serum creatinine levels less than or equal to 1.5 mg/dl), we compared morphological findings and renal function in 100 adult patients with IgA nephropathy similarly distributed in each decade of age including over 60 y.o.. The following histological parameters were investigated; glomerular sclerotic index calculated a mean for total glomeruli, tubulointerstitial damage or interstitial volume measured by the point-counting method, luminal narrowing index by intimal thickening of arterioles determined morphometry. Tubulointerstitial damages were significantly correlated to aging with a direct linear worsening. Luminal narrowing of arterioles rapidly worsened with age after 40 y.o. who were frequently associated with chronic hypertension. The patients over 60 y.o. had a significant correlation between luminal narrowing of arterioles and glomerular sclerotic index, though those were statistically no related in patients less than 60 y.o.. Glomerular sclerotic index was significantly related with tubulointerstitial damage at all decades except for thirtieth decade. Serum creatinine level was well correlated with glomerular sclerotic index and tubulointerstitial damage, respectively; increase of those indices may indicate poor prognosis. We concluded that ischemic glomerular sclerosis by mean narrowing of afferent arterioles may appear after 60 y.o., probably due to insufficiency of autoregulation for glomerular circulation. Luminal narrowing of arterioles in patients less than 60 y.o. may not reflect to be a main cause for ischemic damage of glomerulus. Therefore it may not be a indicator for renal prognosis in patients with IgA nephropathy less than 60 y.o. PMID- 2214316 TI - [Ristocetin induced platelet aggregation in children with nephrotic syndrome]. AB - In 22 children with steroid responsive nephrotic syndrome (SRNS), we examined platelets aggregability to ristocetin, and the data obtained wre compared with negative charge on platelet membrane based on the binding of cationic dye alcian blue 8GX (AB) or plasma levels of von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor (Rcof) activity. At the initial or relapse stage of SRNS, the enhanced platelet aggregation to ristocetin was observed, and correlated with the decreased alcian blue binding to platelets. Ristocetin-induced vWF:Ag binding to platelets by using 125I-vWF was significantly increased. In addition, ristocetin induced platelets aggregation (RIPA) using washed nephrotic platelets still enhanced as found in the patient's platelets rich plasma (PRP), even when it was resuspended into normal plasma. These results suggest that the decrease of platelet surface negative charge play an important role of heighten RIPA found in children with SRNS. PMID- 2214317 TI - [Study on the pathogenetic factors of the progression of renal insufficiency, with special reference to the effects of dietary protein intake]. AB - The effects of dietary protein intake on the progression of renal insufficiency were studied in daunomycin (DMC) induced nephrotic rats (DMC rats) and also patients with chronic renal diseases. In the first study, the author examined which treatment among enalapril (E) and indomethacin (I) and dietary protein restriction was the most effective to prevent proteinuria and glomerulosclerosis, and then the effect of dietary protein restriction on renal content of malondialdehyde (MDA) and superoxide dismutase (SOD) in DMC rats. These rats were divided into four groups as follows: group PL and group PH were isocaloric diets containing either 5% or 24% protein, respectively and group PE and PI were given orally E (100 mg/l drinking water) or I (50 mg/l drinking water) with diets of 24% protein, respectively. In group PL, urinary protein excretion (U-Protein) rates and renal damage index were significantly lower than those in other three groups. In group PE, renal damage index was significantly improved although U Protein showed no reduction in contrast with these in group PH. Renal MDA in group PL was lower than that in group PH was significantly lower than that in group PL. In this study dietary protein restriction was the most effective treatment for the prevention of progressive renal insufficiency. In the second study, patients with chronic renal diseases were divided into two groups according to their Ccr: group I; Ccr greater than or equal to 60 ml/min, group II; Ccr less than 60 ml/min. All patients orally received diets of high protein (1.4 g/kgBW) and subsequently of low protein (0.7 g/kgBW). Ccr, U-Protein, serum MDA and serum SOD were estimated at the end of each dietary period. In group I, Ccr was significantly lower on low protein diet than that on high protein diet, although these were no significant changes in Ccr in group II. The low protein diet caused a significant decrease in U-Protein in both groups. Serum MDA in group I was significantly lower on low protein diet than that on high protein diet, but not in group II. Serum SOD activity showed no changes. It is suggested that dietary protein restriction might reduce oxidant stress to the kidney, in addition to renal hemodynamic changes induced by prostaglandin and renin angiotensin system, resulting in the prevent of progress of renal insufficiency. PMID- 2214318 TI - [The criteria for indication of plasma exchange on lupus nephritis]. AB - Although many reports have been made on the effectiveness of plasma exchange (PE) in active systemic lupus erythematosus (SLE), but there are no clear-cut criteria of indication for lupus nephritis (LN). In order to determine the criteria for indication of LN, 35 patients with LN treated by PE were studied with respect to renal function (F), proteinuria (P), immunological activity (A) and renal histology. The patients were divided into 4 groups according to the severity of renal function: F1 (stable chronic renal failure (CRF) or stable renal function n = 13), F2 (relapse type n = 9), F3 (rapidly progressive LN; creatinine clearance (Ccr) less than 40 ml/min n = 7) and F4 (acute renal failure; Ccr less than 10 ml/min n = 6). Proteinuria was also studied in 4 groups: P1 & P2 (without nephrotic syndrome (NS], P3 (acute type NS n = 15), and P4 (chronic type NS n = 7). These patients were divided into 3 groups to study immunological activity: A1 (chronic stage n = 6), A2 (relapse stage n = 12) and A3 (active stage n = 17). Comparison was made in each parameter. Renal histological classification according to WHO criteria of LN, activity score (AS) and chronicity score (CS) were evaluated and compared. As a result, the following indication was obtained. 1) ABSOLUTE INDICATION: 1. Rapidly progressive LN with high immunological activity; elevated serum creatinine (SCr) greater than 1.0 mg/dl/month or decreased Ccr from normal renal function to less than 40 ml/min within 1-2 months after onset. 2. Acute type NS within 1 year after onset. 3. histological AS greater than 20. 2) RELATIVE INDICATION: 1. Relapse LN with moderate immunological activity, decreased Ccr from normal function to 40-50 ml/min within 3-6 months, the rise in SCr of greater than 1.0 mg/dl/month. 2. Proteinuria is 1.0-3.5 g/day within 1 year after onset. 3. Such complication as CNS, serositis, thrombocytopenia and leukopenia, steroid resistance and/or severe side effects of steroid. 3) NO INDICATION: 1. CRF or stable renal function (Ccr greater than 50 ml/min). 2. Chronic type NS over 1 years with past history of NS and/or edema. 3. Low immunological activity and mild renal histology. PMID- 2214319 TI - [The diagnostic critical value in DFO low dose loading test on patient with aluminum accumulation compared to each parameter of ROD]. AB - One hundred two hemodialyzed patients were examined to determine the standard level of delta Al value which is the difference of serum Al concentrations between pre and post DFO loading test. We applied low dose of DFO 15 mg/kg in this loading test. Some significant negative correlations were found between delta Al and MCI, sigma GS/D, osteocalcin, free-Hydroxyproline (dialysate) and free-gamma-Carboxyglutamic acid (dialysate). Each correlation rate was -0.58, 0.44, -0.76, -0.57 and -0.51 respectively. In addition tendencies of correlation were found between delta Al and ALP and between delta Al and %QCT (QCT/mean QCT in patient's age x 100). And statistical significant differences were found between (0 less than delta Al less than or equal to 150 micrograms/l) group and (150 micrograms/l less than delta Al) group in each osteobiochemical parameter. These results indicate that 150 micrograms/l is the lower diagnostic standard level of delta Al in 15 mg/kg DFO loading test. PMID- 2214320 TI - [High deposition rate of aluminum in tissues in diabetic hemodialysis patients]. AB - Aluminum (Al) accumulation in bone is a serious problem in patients on hemodialysis. We studied deferoxamine infusion test (DFO test) in 14 diabetic patients on hemodialysis (HDDM) and 23 hemodialysis patients originated from glomerulo nephritis (HDCGN) to determine whether Al accumulation is different between the two groups or not. There was no difference in hemodialysis duration and total oral intake of Al containing drugs between two groups. Serum C-terminal parathyroid hormone (C-PTH) in HDDM was lower than that in HDCGN group (1.82 +/- 1.30 vs. 3.80 +/- 1.82 ng/ml; P less than 0.01). However serum Al (s-Al) levels were comparable (61.9 +/- 53.0 vs, 45.0 +/- 32.3 micrograms/l). A significant correlation was observed between duration of dialysis period and s-Al in HDDM (r = 0.806, p less than 0.01), but in HDCGN, the relation was not significant. The patients in HDDM whose cumulative aluminum intake was less than 2.0 kg showed the higher serum A1 concentrations before DFO and greater increases in s-Al after DFO test, as compared with those in HDCGN with matched aluminum intake (93.8 +/- 67.6 vs. 35.9 +/- 23.6 micrograms/l; p less than 0.001 and 141.2 +/- 81.8 vs. 70.3 +/- 41.1 micrograms/l; p = 0.035). These results indicate that in uremic diabetic patients with lower intake of Al containing drugs, an early accumulation of Al in the whole body occurs possibly because of the enhanced absorption rate of Al at an intestine and/or the low PTH level. PMID- 2214321 TI - [Acute renal failure with lactic acidosis]. AB - This study examined the acid base disturbances in 18 adults with acute renal failure (ARF) from one of new aspects, which is lactate metabolism and pathophysiology. 10 patients (55%) of them were accompanied by lactic acidosis and 9 patients (90%) of those with lactic acidosis also had severe hepatic failure. Mortality of patients with lactic acidosis was 80%, and much higher than that of ARF (66.7%). Lactate, pyruvate, lactate-to-pyruvate ratio (L/P) were 76.7 +/- 15.66 mg/dl, 3.30 +/- 0.74 mg/dl and 19.9 +/- 1.41, respectively. All of them significantly raised, compared to values of healthy adults, patients with liver cirrhosis, chronic renal failure and diabetes mellitus. Arterial pH and HCO3- levels were 7.20 +/- 0.04 and 10.6 +/- 1.20 mEq/l. Anion gap (AG) was 30.0 +/- 3.66 mEq/l. Significant correlations of lactate with pH, HCO3-, AG and L/P were demonstrated, while correlations of lactate with BUN, CR and prothrombin time were not significantly observed. Lactic acidosis results from two mechanisms. One is lactate overproduction (e.g tissue hypoxia) and the other is lactate underutilization (e.g severe liver and/or renal failure). Whenever lactic acidosis occurred, both mechanisms were present simultaneously and continuously. Especially, the latter mechanism had a very important role on it, and seemed to decide the prognosis of the patients with lactic acidosis. Therapy of lactic acidosis was very difficult. First of all, we tried to improve the circulatory failure and severe acidemia (pH less than 7.20) not to fall into vicious cycle. Then, CAVH, if combined with alkali infusion, seemed to be the most useful technique in managing lactic acidosis with ARF. PMID- 2214322 TI - [Unfolded map of coronary artery territories by myocardial SPECT]. AB - Coronary artery territories were evaluated precisely by Bull's-eye and unfolded map generated from myocardial SPECT. In addition, unfolded maps including apical information were also developed. The coronary artery territories were determined by 54 cases of typical single vessel disease (more than 75% stenosis) with myocardial infarction and angina pectoris. There were 12 of right coronary artery disease, 24 of left anterior descending coronary artery disease, 5 of diagonal coronary artery disease, and 13 of left circumflex artery disease. Each diseased region was summed and normalized using the standard pattern (21 cases of normal male and 13 cases of normal female). Apical information was simply obtained using the anterior and posterior count from short and long axial image. Then, their data were added to the unfolded map. In conclusion, unfolded map was proven to be useful for the determination of coronary artery territory, since this map expressed the extent and site of myocardial damage precisely compared to Bull's eye. The unfolded map to contain the apical information was also useful for the evaluation of left anterior descending coronary artery involvement. PMID- 2214323 TI - [Clinical evaluation of coronary territory map by using unfolded map of Tl-201 myocardial SPECT]. AB - Coronary territory map was developed on unfolded map of exercise Tl-201 myocardial SPECT. Each coronary territory was determined by summing the each unfolded map of 54 cases of single vessel disease respectively, and standardizing with normal pattern obtained from normal patients. The diagnostic accuracy of coronary territory map to identify the diseased coronary artery was analyzed in 104 clinical cases and was compared with that of planar and SPECT visual diagnosis, simple unfolded map (raw map) and extent & severity map. The results were as follows; 1) Territory map showed excellent diagnostic accuracy in single or double vessel disease, especially in diagnosis of left circumflex coronary artery lesion. 2) In triple vessel disease, the diagnostic accuracy of territory map or other unfolded maps was 30% at best, and was inferior to planar or SPECT visual analysis. The cause of this inferiority seemed that the quantitatively analyzed map had no information about the degree of Tl-uptake into lung or myocardium, which give useful information in visual diagnosis. 3) The diagnostic agreement ratio in two observers was the highest in territory map diagnosis, so that the territory map diagnosis seemed to be the most objective one. 4) The unfolded map diagnosis with apical display obtained from long-axis tomogram was useful to diagnose left anterior descending coronary (LAD) lesion, which improve not only the sensitivity of LAD but also specificity of right coronary artery single vessel disease. PMID- 2214324 TI - [Relationship between the occurrence of late potential and the location and size of myocardial infarction evaluated by thallium-201 SPECT]. AB - High-frequency, low amplitude signals, late potentials (LPs), in the terminal portion of the body surface QRS of the signal-averaged ECG were frequently observed in ventricular tachycardia (VT) following myocardial infarction (MI). In this study, we evaluated the correlation between the occurrence of LPs and the size and location of MI estimated by Thallium-201 myocardial SPECT in 30 MI patients. The positive LPs were identified by the value of %RMS 40, the percent ratio of the root mean square voltage in the last 40 msec of the QRS complex to that of the total filtered QRS from the signal averaged ECG using bipolar X, Y, Z leads. The spatial distributions of LPs were evaluated by the LP30 area maps obtained by the body surface mapping using forty-five unipolar electrodes. Sixty projections were obtained over 180 degree by rotating gamma camera after 5 minutes intravenous injection of 74 MBq of Thallium-201. After low-pass filtering, images were reconstructed into short-axis, horizontal long-axis and vertical long-axis tomograms. The maximum count circumferential profiles for each short-axis cuts were generated from the apical to basal cut and they were expressed into two-dimensional polar functional maps (apex to the center), Bull's eye map, to represent myocardial Tl distribution. Normal limits of myocardial Tl distribution were established as the mean minus 2 standard deviation from those of normal subjects. The MI size was estimated as defect volume ratio (DVR), the percent ratio of abnormal region to that of total volume of left ventricle. Significant differences in DVR were observed among MI with LPs and without LPs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214325 TI - [Experimental study on liver accumulation of N-isopropyl-p-iodoamphetamine]. AB - In order to clarify the mechanism of N-isopropyl-p-iodoamphetamine (IMP) liver accumulations, liver dynamic study by the portal injection of 123I-IMP and liver microautoradiography by 125I-IMP were performed using 5, 2 male rats, respectively. The initial uptake of 123I-IMP in the liver was very high and thereafter 123I-IMP showed relatively rapid wash-out (count ratio of lung to liver at 10 min after the injection was 0.12, 0.15). On the other hand, the addition of 5 mg, 8 mg ketamine hydrochloride decreased the initial 123I-IMP liver uptake and its lung accumulation was noted immediately after the injection (count ratio of lung to liver at 10 min was 0.20). Microautoradiography of the liver using 125I-IMP showed grain density in the central vein and sinusoids, but not in the liver parenchymal cell. These results suggest that non-specific amine receptor (binding site) may exist in the endothelial cell in the central vein, although the number of experimental rats in this series was small for conclusion. PMID- 2214326 TI - [Assessment of myocardial damage in cardiomyopathy using 111In-antimyosin Fab myocardial scintigraphy]. AB - 111In-antimyosin Fab (AM) myocardial scintigraphy was carried out in (A) 10 patients with idiopathic dilated cardiomyopathy, (B) 7 with dilated phase of hypertrophic cardiomyopathy and (C) 8 with normal (control) individuals. Imaging was taken 48 hours after intravenous injection of 74 MBq of AM. Myocardial uptake of AM was evaluated qualitatively and quantitatively. Positive uptake was observed in 9/10 (90%), 7/7 (100%) and 0/8 (0%) in group A, B and C, respectively. AM index (heart/lung ratio) in group A and B were 2.04 +/- 0.24 and 2.46 +/- 0.49, values significantly higher than that obtained in the control patient without cardiomyopathy (1.51 +/- 0.13) (p less than 0.01). Positive monoclonal antimyosin antibody studies were highly prevalent in dilated cardiomyopathic and dilated phase of hypertrophic cardiomyopathic patients, even in the presence of negative right ventricular biopsy. It is suggested that this method was useful for the noninvasive assessment of active myocardial damage in these patients. PMID- 2214327 TI - [Remote effects in cerebral infarction--123I-IMP SPECT study]. AB - We studied the remote effects in 29 patients with middle cerebral artery territory infarction by using single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]iodoamphetamine. SPECT demonstrated a reduction in blood flow in the cerebellar hemisphere contralateral to the cerebral infarct, the cortex ipsilateral to the subcortical infarct, the visual cortex distal to the optic radiation lesion, and the thalamus ipsilateral to the cortical infarct. In addition to transient neuronal depression identified with diaschisis, our results indicated that persistent phenomena were apparently involved in these remote effects. The degenerative processes might be related to irreversible effects in remote areas. Clinical symptoms corresponding to the areas of hypoperfusion remote from infarcted lesions were not necessarily present. PMID- 2214328 TI - [Regional myocardial blood flow measurements in resting and dipyridamole induced vasodilative state by Xenon-133 clearance method]. AB - Myocardial imaging with Xenon-133 and a gamma camera was employed to evaluate the relationship between angiographically demonstrated coronary artery stenosis and regional myocardial blood flow (r-MBF) in 22 patients with ischemic heart disease and 9 control subjects. After a left anterior oblique cineangiogram was obtained, the cinecamera was replaced by the mobile gamma camera in the same plane and location over the pericardium of patients. Then, 370 MBq (10 mCi) of 133Xe was injected into the left coronary artery as a bolus. After the first measurement of r-MBF in resting state, a second injection was made 3 minutes after intravenous injection of 0.56 mg/kg of dipyridamole for 4 minutes. The r-MBF in different regions of the heart was calculated by Kety formula. Coronary flow reserve (CFR) was defined the rMBF ratio between resting and dipyridamole induced vasodilative state. In the resting state, good correlation (r = 0.711) was observed between pressure rate product and the r-MBF at the areas perfused by non stenotic vessels. The r-MBF of the areas perfused by severe stenotic vessels (greater than 90%) was smaller than that of the areas perfused by non stenotic vessels, however there was overlapping of flow. In the dipyridamole induced vasodilative state, the r-MBF of the areas perfused by intact vessels increased approximately 2.4 times of the resting state, and showed good correlation with pressure rate product. In contrast, the r-MBF of the areas perfused by stenotic vessels did not correlate with pressure rate product, but depended on the degrees of coronary stenosis (50-75% stenosis; 1.9 times, greater than 90% stenosis; 1.3 times, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214329 TI - [Brain glucose metabolism in a patient with Creutzfeldt-Jakob disease measured by positron emission tomography]. AB - Sequential measurements of local cerebral glucose metabolism were performed in a case with Creutzfeldt-Jakob disease. The diagnosis was based on the characteristic clinical symptoms and EEG. Cerebral glucose metabolism (CMRGlc) was measured by positron emission tomography (PET) and 18F-fluorodeoxyglucose. CMRGlc was decreased to about 45% of the normal value. At that time, X-ray CT revealed little brain atrophy. The decrease of CMRGlc was prominent in cerebral cortices, but the metabolic decrease was slight in striatal body, cerebellum, and brainstem. The motor cortex and occipital lobe showed relatively preserved metabolism among the cerebral cortices. Six months after the first PET measurement, X-ray CT showed marked brain atrophy. Decrease of cerebral glucose metabolism advanced furthermore. However, the progress of the decrease was relatively small in the basal ganglia, brainstem, and cerebellar nucleus. These findings differ from the findings that was known by pathological study. These results suggest that measurement of CMRGlc by PET is useful for the early detection and for understanding of the pathophysiology of this disease. PMID- 2214330 TI - [Fundamental and clinical evaluation of ELSA CA 72-4 kit for serum CA 72-4 antigen]. PMID- 2214331 TI - [Anthropological research method. Commentary: anthropological research method of clinical problems]. PMID- 2214332 TI - [Anthropological research method. How to use anthropological methods in nursing research]. PMID- 2214333 TI - [Anthropological research method. Ethnonursing: the nursing research method to generate transcultural nursing knowledge]. PMID- 2214334 TI - [Anthropological research method. A description of the diet habits and and their related factors among people who keep a special diet "Syoku-youjou"]. PMID- 2214335 TI - [Anthropological research method. Facing life transitions in an alien culture: the case of American women giving birth in Japan]. PMID- 2214336 TI - [Anthropological research method. Cultural construction of the menopausal syndrome: the Japanese case]. PMID- 2214337 TI - [Anthropological research method. Research and the process about "modern midwives"]. PMID- 2214338 TI - [The approach to the English monograph. To challenge your translation: to discover your mistakes (5)]. PMID- 2214339 TI - Calcium and disease. PMID- 2214340 TI - Complete atrioventricular block following radiation therapy for malignant thymoma. AB - Complete atrioventricular block following radiation is very rare. We present a case which developed after radiation therapy for malignant thymoma. The etiology of conduction disturbances due to radiation is unknown. In our case, serial electrocardiograms showed stepwise progression of the conduction disturbance, and His bundle electrocardiograms revealed new prolongation of the H-V interval. Endomyocardial biopsy specimens demonstrated occlusion in small arteries and diffuse degenerative changes in the myocardium. We therefore attributed the complete atrioventricular block in our patient to secondary damage to the conduction system, caused by radiation-induced occlusive changes in the small arteries supplying the conduction system. PMID- 2214341 TI - Spontaneous fall in blood pressure and reactivity of sympathetic nervous system in hospitalized patients with essential hypertension. AB - We evaluated whether reduction in sympathetic reactivity plays a major role in the spontaneous falls in blood pressure (BP) experienced during hospitalization by patients with essential hypertension. In the present case BP fell on the 2nd day of hospitalization. The responses of plasma catecholamines (CA) and BP to both handgrip and tilting were not altered during either the first 24 hours or the entire 7 days of hospitalization. The effect of phentolamine on BP was similar on the 1st, 2nd and 7th days. However, the resting levels of plasma norepinephrine before handgrip, tilting and phentolamine were significantly diminished on the 7th day, but not on the 2nd day. In conclusion, the diminution of sympathetic activity may be partly responsible for the hospitalization-induced fall in BP in the late stages. PMID- 2214342 TI - Beta 0-thalassemia due to a nonsense mutation at beta 90 (GAG----TAG) in human hemoglobin gene. AB - We studied a patient with severe anemia and jaundice who exhibited a high hemoglobin A1 (HbA1) level secondary to an increase in HbF despite normal glucose tolerance. The red blood cells showed anisocytosis, poikilocytosis and polychromasia; target cells, Howell-Jolly bodies, Heints bodies and punctate basophilia were observed. No defect or reduction in activity was observed in 19 red cell enzymes. A family history of similar anemia in the patient's daughter and cousins on the mother's side indicated an involvement of genetic factors. Gene cloning and DNA analysis showed that the condition is a new type of beta 0 thalassemia caused by a nonsense mutation (GAG----TAG) in codon 90 of the beta globin gene. PMID- 2214343 TI - A case of a clinically "silent" pheochromocytoma. AB - A case of a clinically "silent" pheochromocytoma is presented. The adrenal mass was incidentally discovered by abdominal ultrasonography and computed tomography. In the course of hospitalization, the patient was normotensive and asymptomatic. Plasma catecholamine levels were nearly normal, whereas urinary levels of catecholamine metabolites were slightly elevated. A glucagon provocative test and 131I-metaiodobenzylguanidine scintigram were useful for diagnosing such an atypical pheochromocytoma. A discussion of clinically-unsuspected pheochromocytoma is also presented. PMID- 2214344 TI - Primary osteogenic sarcoma of pulmonary artery. AB - A 44-year-old woman was hospitalized for nonproductive cough. Chest roentogenogram revealed a calcified nodular mass at the right hilum. The patient was treated as tuberculosis of the hilar lymph node, however, her symptoms exacerbated within a year. A tumor obstructing the right main stem bronchus was demonstrated on bronchofiberscopic examination. Thoracotomy was carried out and tumor was diagnosed as primary osteogenic sarcoma of the pulmonary artery by pathological examination of the resected specimen. There was no clinical finding of osteogenic sarcoma throughout the bones. PMID- 2214345 TI - A case of polymyositis associated with chronic thyroiditis presenting as hyperthyroidism. AB - We describe a case of polymyositis associated with hyperthyroidism (Graves' disease). Clinical findings and thyroid function tests revealed hyperthyroidism. On histological examination, it was found that the thyroid gland was involved in chronic thyroiditis, and no appearance of Graves' disease was noted. This case suggested that the patient's muscle weakness might have been related to a disturbance of thyroid function, that is, coexistence of subclinical thyrotoxic myopathy. There were fluctuations in the levels of various antibodies during the clinical course of this overlap syndrome. PMID- 2214346 TI - Water intoxication and rhabdomyolysis. AB - A 44-year-old woman was admitted because of stupor. She had consumed 3 liters of water due to thirst after drinking alcohol. Laboratory findings on admission revealed marked hyponatremia (sodium: 115 mEq/l). She was diagnosed as having water intoxication. She recovered from her hyponatremia upon excretion of a large amount of hypotonic urine. Subsequently, however, her serum creatine phosphokinase was markedly elevated at 28,650 IU/l, and her serum myoglobin reached 2,760 ng/ml. The relationship between the occurrence of hyponatremia secondary to water intoxication and rhabdomyolysis was suggested. PMID- 2214347 TI - An adult case of acute lymphoblastic leukemia with necrotizing leukoencephalopathy. AB - A 19-year-old man with common acute lymphoblastic leukemia (ALL) developed necrotizing leukoencephalopathy (NL) after extensive chemotherapy and irradiation. Clinicians should exercise care in the treatment of leukemia, since chemotherapy has shown a trend of becoming more intensive, and the survival time of patients with leukemia is being extended. PMID- 2214348 TI - Familial amyloidotic polyneuropathy in Hokkaido: a case report. AB - A 54-year-old man began to feel numbness in his hands at the age of 42 (1975). His condition became progressively worse accompanied by muscle weakness of the lower limbs and glove and stocking paresthesia of the extremities. The patient was admitted to our hospital on March 23, 1987. Neurological examination revealed distal dominant muscle weakness, sensory disturbance and areflexia. Electrocardiogram and ultrasound-cardiogram strongly suggested cardiomyopathy. A biopsy of the rectal wall and the cardiac muscle revealed amyloid deposits. The patient, his elder brother and one of his daughters had abnormal serum transthyretin (TTR, a protein referred as prealbumin). Therefore, the diagnosis of familial amyloidotic polyneuropathy (FAP) was confirmed. The patients's brother and daughter mentioned above, however, had no abnormal findings on physical examination and they were thus considered to be asymptomatic carriers. There may be more cases of asymptomatic carriers, if examination of abnormal TTR is more frequently analyzed. PMID- 2214349 TI - Vitiligo with primary hypothyroidism and hypoacusis: a case report. AB - A 48-year-old female patient with vitiligo developed primary hypothyroidism and hypoacusis. The signs and symptoms of hypothyroidism improved with thyroid hormone replacement therapy but hypoacusis did not. The coexistence of vitiligo and thyroid disease is uncommon and the additional association of hypoacusis is very rare. There may be a common autoimmune pathogenesis for the three disorders. Vitiligo may be a diagnostically useful sign which suggests the presence of multiple autoimmune diseases. PMID- 2214350 TI - Presence of Philadelphia (Ph) chromosome-negative cells in Ph-positive chronic myelogenous leukemia. AB - Six cases of chronic myelogenous leukemia (CML) with coexistence of cells with a Philadelphia (Ph) translocation and a normal karyotype are described. Molecular analyses were performed in 3 of the 6 cases at two phases with different cytogenetic findings. Among the 6 cases, 4 cases were late appearance of a Ph chromosome. Two of the 3 patients analyzed had major breakpoint cluster region (Mbcr) rearrangements; aberrant Mbcr fragments were observed whether the cells had a Ph translocation or not. The remaining one did not show any rearrangements within the Mbcr DNA sequences. PMID- 2214351 TI - Transplacental passage of autoantibodies from a mother with diabetes and Graves' disease to her infant. AB - Antibodies to islet cells and thyroid gland were examined in a mother with insulin-dependent diabetes mellitus and Graves' disease and in her infant. Islet cell antibodies (ICA), complement-fixing ICA, islet cell surface antibodies (ICSA) and anti-microsomal antibodies (MAb) persisted in the mother during pregnancy. At birth, ICA, ICSA and MAb could be detected in the infant. ICSA and ICA in the infant disappeared by the 3rd and 7th months, respectively. There was no clinical or laboratory evidence of diabetes in the infant. These data suggest that anti-islet cell antibodies themselves may have no significant effect on islet cells. PMID- 2214352 TI - Two cases of Reiter's syndrome. AB - Two characteristic cases of Reiter's syndrome are reported. One (case T.M) was a 64-year-old female with ulcerative colitis and the other (case O.M) was a 20-year old male with serum antistreptococcal lysine O (ASLO) and antistreptokinase (ASK) titers of 480x and 2560x, respectively. These cases were both histocompatibility antigen HLA-B27 positive. The ulcerative colitis and iritis were inactive in case T.M. However, case O.M required aggressive treatment for fever and arthralgia. These patients have recently shown no evidence of Reiter's syndrome; however, case T.M has had recurrent bowel hemorrhages due to ulcerative colitis. PMID- 2214353 TI - Overwhelming pneumococcal pneumonia in a patient receiving ofloxacin for antimicrobial prophylaxis. AB - A case of severe bacteremic pneumococcal pneumonia which developed in a patient with lung cancer, who was taking ofloxacin for chemoprophylaxis, is presented. Pneumonia resolved well with intravenous penicillin G. Infection by and colonization with Streptococcus pneumoniae might become a problem with increasing use of the fluoroquinolones. PMID- 2214354 TI - A case of relapsing polychondritis associated with hemolytic anemia. AB - Relapsing Polychondritis (RPC) is a rare disorder of unknown etiology which affects mucopolysaccharide-rich tissues such as cartilage. A 64-year-old man developed auricular and nasal chondritis with complaints of arthralgia of the hands and cervical pain. The auricular biopsy established the diagnosis of RPC. The hematological data revealed normocytic, slightly hypochromic anemia, a persistently elevated reticulocyte count, slightly increased bilirubin, and decreased haptoglobin. The presence of hemolytic anemia was confirmed by the shortened half-life of erythrocytes and erythroid hyperplasia of the bone marrow. This case illustrates the coexistence of RPC and hemolytic anemia which has been only rarely reported. The pathogenesis of RPC is also discussed may elucidate the pathogenesis of this disease. PMID- 2214355 TI - Carnitine deficiency following massive intestinal resection: a morphological and biochemical study. AB - A 65-year-old man with progressive muscle weakness and liver dysfunction following massive small bowel resection showed myriad lipid-filled vacuoles in type I muscle fibers. Carnitine was significantly decreased in muscle, serum and urine. Carnitine supplementation was followed by clinical improvement and decreased lipid droplets in biopsied muscle. He had been receiving carnitine deficient total parenteral nutrition. This form of carnitine deficiency may be due to a defect in carnitine biosynthesis, as well as dietary carnitine deficiency. PMID- 2214356 TI - Herpes zoster ophthalmicus with delayed contralateral hemiparesis. AB - A 35-year-old previously healthy woman developed left hemiparesis sixteen weeks after the onset of right herpes zoster ophthalmicus. Cerebral angiography showed complete occlusion of right middle cerebral artery at the origin and segmental narrowing of the right posterior cerebral artery. Computerized tomography (CT) and magnetic resonance imaging (MRI) also revealed a right hemispheric lesion consistent with angiographic findings. Reports from the literature along with the present case suggest that arteritis followed by cerebral infarction is the most probable cause of delayed contralateral hemiparesis. PMID- 2214357 TI - Fluid movement across the blood-retinal barrier: a review of studies by vitreous fluorophotometry. AB - Vitreous fluorophotometry was used to study the fluid movement across the blood retinal barrier. The effect of plasma osmolality and intraocular pressure on the movement of the fluorescent tracer confirmed the interaction between the tracers and the fluid flow across the blood-retinal barrier. The measurement of outward and inward permeabilities to carboxyfluorescein revealed the existence of a posteriorly directed fluid flow in the vitreous cavity of cynomolgus monkey eyes with retinal detachment. Fluid movement across the blood-retinal barrier was shown to be inhibited by furosemide and enhanced by acetazolamide. Furthermore, vitreous fluorophotometry proved to be useful in estimating the in vivo fluid dynamics in the vitreous and across the human retina. PMID- 2214358 TI - Flash electroretinograms and pattern visually evoked cortical potentials in Behcet's disease. AB - Behcet's disease with posterior uveitis was studied in 12 cases by flash electroretinography (FERG) and pattern visually evoked cortical potential (PVECP). Disappearance of oscillatory potentials was the initial change noted in FERG. Subnormal FERG and a delay in peak latency of the P100 component of PVECP were observed in patients with poor visual acuity and long-standing Behcet's disease. Amplitudes of PVECP were significantly decreased in these patients. It was suggested that FERG together with PVECP were good indicators for monitoring posterior segment changes and visual prognosis in Behcet's disease. PMID- 2214359 TI - Studies of experimentally induced retinal degeneration: 2. Early morphological changes produced by lipid peroxides in the albino rabbit. AB - When pure, synthetic lipid hydroperoxides (LHP) were injected into the vitreous body of albino rabbits, electrical activity was decreased in all components of the electroretinogram (ERG) in a progressive and time-related manner. In the early phase morphological changes occurred at the interface between the photoreceptor outer segments and the retinal pigment epithelium (RPE) in response to LHP. These findings commenced within a few hours after injection and continued during the following 2-3 weeks, when the ERG was completely extinguished. Two days after injection, the rod outer segments (ROS) were swollen and damage of the RPE apical villi was observed. This initial event was followed by additional changes in the RPE which embraced swelling, accumulation of residual bodies, complete loss of ROS and enlargement and disruption of Bruch's membrane. The precursors of residual bodies appeared to result from focal, peroxidative damage to ROS discs which apparently rendered these materials undegradable by the RPE. As ROS degeneration continued, the RPE showed hypertrophy and modification. These studies provided evidence for a sequential destruction of the neural retina and RPE during oxidative damage involving lipid peroxidation. The mechanism appeared to differ from that produced by other toxic compounds or those which resulted from vitamin E or A deficiency. This new model system is thought to be useful in 1) explaining differences in susceptibility of inner ROS disks versus other membranes, 2) determining how the RPE metabolizes abnormal ROS, 3) studying RPE reactivity following trauma and/or retinal detachment, and 4) determining factors which produce degeneration of Bruch's membrane. PMID- 2214360 TI - Retinal nerve fiber layer analysis by a computerized digital image analysis system. AB - A computerized digital image analysis system was developed to evaluate the retinal nerve fiber layer (RNFL) by red-free fundus photography. The image intensity of the RNFL was computed for 30 degrees between the disc and macula. Thirty early open-angle glaucoma patients and 30 normal age-matched subjects were examined. The coefficients of variation in the reproducibility of the measurements in normal subjects were 7.3 to 9.9% for the interphotographic studies, and 4.1 to 5.1% for the intraphotographic studies. Using this new image analysis system, the RNFL changes were detected easily and the glaucomatous eyes were distinguished from normal eyes with high sensitivity and specificity, 95% and 80%, respectively. This method will be useful for diagnosis of glaucoma at a very early stage. PMID- 2214361 TI - Pseudopodia of capillary endothelium in ocular tissues. AB - The frequencies of pseudopodia projecting from capillaries of various parts of the eye were observed in 16 human eyes with a transmission electron microscope. The pseudopodia were found mainly projecting from the choriocapillaris and rarely seen in the retina, iris or ciliary body. The frequencies of pseudopodia from the choriocapillaris were not correlated with the localization in the fundus (macular area or peripheral fundus), age, sex, time elapsed between death or enucleation and fixation. The significance of pseudopodia from the choriocapillaris is unknown. However, there is the possibility that pseudopodia are related to choroidal neovascularization or have other physiological functions. PMID- 2214362 TI - H2O2-dependent NADH oxidation activity in senile cataractous human lens: its relation to glutathione redox cycle. AB - The present study has demonstrated that H2O2-dependent NADH oxidation activity in aged transparent and senile cataractous human lenses is due to a glutathione redox cycle which consists of reduced glutathione, oxidized glutathione, glutathione peroxidase and glutathione reductase. Especially, the NADH oxidation activity was proportional to the content of free glutathione (reduced plus oxidized forms) under our assay conditions. Employing this simple assay method, the present report has also shown that in the aged and cataractous lenses with pale yellow, yellow or dark yellow nucleus, the free glutathione contents tend to decrease with the increase of insoluble protein contents. However, lens protein was remarkably insolubilized in the lenses with cataracta brunescens, regardless of their exhibiting low or high glutathione contents. The relationship among protein aggregation, coloration and glutathione concentration in the cataractous lenses has been discussed from these findings. PMID- 2214363 TI - Histochemical studies of mitochondrial activities of cultured corneal endothelial cells of cat during wound-healing. AB - The corneal endothelial cells of the cat were cultured, and in 3 weeks the cells became confluent and formed a cell sheet. The cells were stained with rhodamine 123 and nitroblue tetrazolium (NBT). The frequencies of cells stained by these two methods changed during the 3-week culture, but at the end of the culture the frequencies were stabilized at 58 +/- 3.9 (mean +/- SD) % for the rhodamine 123 staining method and 35 +/- 3.7% for the NBT method. An oval wound of 600 X 400 microns was made in the center of the cultured endothelial cell sheet, and the cell migration was observed by phase contrast microscopy. Six hours after the wounding, the cells began to migrate toward the center of the wounded area, and in 24 hours the denuded area was almost completely covered by migrated cells. In 48 hours the wound was tightly covered by the migrated cells. One hour after the wounding, the cells in the wound margin were strongly stained by rhodamine 123, but not by NBT. The cultured cell sheet was divided into 4 concentric areas, ie, S1 was the center of the wound, S2 was the 100-microns-wide zone inside the original wound edge, S3 was the 100-microns-wide zone outside the original wound edge, and S4 was the 100-microns-wide zone outside the S3 zone. Topographical changes in rhodamine- and NBT-stained cells were observed over a 48-hour period. Rhodamine-positive cells increased in the S1 area, while a decrease occurred in the S2 and S3 areas. NBT-positive cells peaked at 12 hours after the wounding and decreased thereafter. It was concluded that the endothelial cells migrating to cover the wounded area showed a significant enhancement of mitochondrial activity, as indicated by the rhodamine 123 staining, but the succinic dehydrogenase activity revealed by NBT staining was rather suppressed. PMID- 2214364 TI - Characterization of water-insoluble proteins in normal and cataractous human lens. AB - The mechanism of lens protein aggregation with age and/or cataract formation was investigated using the peptides resolubilized from the insoluble protein fraction of normal and cataractous human lenses. The insoluble fraction was treated with reductants for cleaving disulfide bonds, or with chelating agents for removing calcium ions from the aggregates. This study demonstrates that the insoluble protein aggregates consist of an approximately 400 Kd complex, which is formed by the peptides with lower molecular weight. Protein aggregation in the cataractous lens might be caused by disulfide bonds whereas, in aging, the aggregate might be preferentially formed by calcium ion bridges rather than by disulfide bonds. It was observed that the aggregate from the cataractous lenses involved a peptide with a molecular mass lower by 1 Kd or 2 Kd than the peptides found in the normal lens. The composition of crystallins in aggregating proteins and their secondary structures were also different in the normal and the cataractous lenses. Such changes of molecular weight, conformation, and/or crystallin species in the lens may lead to the disintegration of the orderly arrangement of crystallins, resulting in the diffused reflection and lens opacities which are seen in senile cataract. PMID- 2214365 TI - Layer-by-layer analysis of macular diseases with objectively measured visual functions. AB - New methods were developed to measure layer-by-layer visual function in macular diseases objectively and quantitatively. A prototype apparatus for foveal cone densitometry that combines a modified fundus camera, independent optic pathways and a personal computer was assembled. Using a two-way density technique, the density and regeneration time of the foveal cone pigment can be measured objectively. Data on layer-by-layer visual function can be obtained when a-wave, b-wave and oscillatory potentials are recorded by focal macular electroretinography (FMERG). Since the retinal origin of each component is different, the comparative measurement of these components indicates which layer of the macula is disturbed. The simultaneous recording of FMERG and visual evoked response (VER) might be useful in determining which part of the visual pathway is impaired. These methods of measurement were reviewed and some examples of layer by-layer analysis were shown. PMID- 2214366 TI - Objective visual acuity testing by optokinetic nystagmus suppression. AB - The features of optokinetic nystagmus (OKN) suppression were investigated in various kinds of visual disturbances including those of optical, retinal, higher cortical and psychogenic etiologies. A new OKN suppression device was developed, modifying the principle of Ohm. Objective visual acuities were calculated using the visual angle of OKN suppression dots which were arranged in 12 steps corresponding to the visual acuity from 0.03 to 1.0 as determined by Landolt's method. A total of 286 cases were tested. Results were classified into four types of coincidence between objective and subjective visual acuities. The first group showed equivalent acuities. Normal subjects, cases of corneal opacity, aphakia with intraocular lens implantation and functional amblyopia belonged to this category. In the second group, objective acuity could not be determined because of fixation disturbance due to cortical lesion. The subjective acuity better than the objective acuity was obtained in the third group which consisted of cases with macular hole, central serous retinopathy and optic neuritis with central scotoma. Disturbance of foveal fixation to the OKN suppression dot seemed to be the reason for this difference in the acuities. In the fourth group, the objective acuity was better than the subjective acuity. This occurred in cases of psychogenic visual disturbance and malingerer. PMID- 2214367 TI - Effects of lidocaine, disopyramide and verapamil on the in vivo triggered ventricular arrhythmia in digitalized canine heart. AB - Triggered activity due to delayed after depolarization has been postulated to be one of the generation mechanisms of some arrhythmias, especially that due to digitalis toxicity. The present experiment demonstrates an in vivo canine model of ventricular arrhythmias that were triggered by ventricular stimulation during administration of low doses of ouabain. Ventricular ectopic beats could be induced by stimulation before the occurrence of spontaneous ventricular arrhythmia, and the coupling interval of the first ectopic beat was shortened as the stimulation rate increased. Verapamil (0.2 mg/kg, i.v.) was ineffective in suppressing the occurrence of the triggered ventricular ectopic beats, but lidocaine (1 and 3 mg/kg, i.v.) and disopyramide (0.3 and 1 mg/kg, i.v.) were effective in suppressing these digitalis-induced triggered ventricular ectopic beats in a dose-dependent fashion. PMID- 2214368 TI - Evaluation of drugs for treatment of urinary bladder dysfunction in conscious rats with intact pelvic nerve and after resection of the left pelvic nerve. AB - We studied the effects of drugs used for treatment of bladder dysfunction in conscious rats with intact pelvic nerves and also in rats at one or two weeks after nerve decentralization on the left side. Bladder contraction accompanying micturition was continuously induced by infusion of solution at a constant rate. When the effects of oxybutynin (3 mg/kg, i.p.) and terodiline (3 and 10 mg/kg, i.p.) on the cystometrogram were studied for about 2 hr, these drugs shortened and then prolonged the micturition interval (MI), but atropine (1 and 5 mg/kg, i.p.), butylscopolamine (20 mg/kg, i.p.) and nifedipine (3 mg/kg, i.p.) exhibited only a shortening effect on the MI. After injection of oxybutynin (10 mg/kg, i.p.), solution dribbled from the urethra for about 30 min. Terodiline (3 mg/kg) caused ischuria in the rats one week after resection of the left pelvic nerve, but not in the rats two weeks after surgery. Physostigmine (0.3 mg/kg, i.p.) improved micturition in the rats one week after surgery, but the effect was not evident in the rats with intact pelvic nerves. It was found that the drugs used for treating failure to store or expel urine exhibited a beneficial effect on micturition in rats with intact pelvic nerves and also in rats one week after nerve decentralization, respectively. PMID- 2214369 TI - Physical dependence potential of an enkephalin analog, EK-399, in rats. AB - The physical dependence potential of Tyr-D-Met(O)-Gly-EtPhe-NHNHCOCH3.AcOH (EK 399), a novel enkephalin analog with a potent analgesic effect, was assessed in rats. The animals were given EK-399 (0.008, 0.032, 0.125, or 0.5 mg/kg), morphine (0.125, 0.5, or 2 mg/kg), pethidine (2 or 8 mg/kg), or pentazocine (2 or 8 mg/kg) every hour through an implanted intravenous cannula. After 3 days of treatment, precipitated withdrawal tests were conducted: naloxone (5 mg/kg) was administered subcutaneously. Rats treated with morphine showed withdrawal signs such as hyperirritability, salivation, diarrhea, and weight loss. Rats treated with pethidine, pentazocine, or EK-399 showed similar signs, but they were less evident than those in morphine-treated rats. In abrupt withdrawal tests after 7 days of treatment, rats treated with morphine, pethidine, or pentazocine showed weight loss, whereas rats treated with EK-399 showed little or no weight loss. In substitution tests, EK-399 suppressed the withdrawal signs in morphine-dependent rats, and vice versa. These results show that EK-399 has a morphine-like physical dependence potential that is weaker than that of morphine, pethidine, or pentazocine in rats. PMID- 2214370 TI - Specific metabolic activation of FK973, a new antitumor antibiotic, in L1210 leukemia cells. AB - FK973 (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11- diazatetracyclo[7.4.1.O2,7O10,12]tetradeca-2,4,6-trien -6,9-diyl diacetate), a new substituted dihydrobenzoxazine, has potent cytotoxic and antitumor effects on murine and human tumors in vivo and in vitro, and forms interstrand DNA-DNA and DNA-protein cross-links after being activated in the cytoplasm. In this study, the mechanism(s) by which FK973 is activated in the cytoplasm of in vitro cultured murine L1210 leukemia cells were studied using compounds that affect monoamine oxidase. When the cells were incubated with an antitumor drug and the compounds, tranylcypromine, benzylamine, phenylethylamine and tyramine of the many compounds tested reduced the cytotoxicity of FK973, but not that of mitomycin C or cisplatin. These compounds also suppressed the formation of interstrand DNA-DNA cross-links with FK973 in the cells, but did not suppress cross-links with mitomycin C or cisplatin. The incorporation of 14C-FK973 into the cells was not affected by these compounds. The results suggest that FK973 is activated by some drug-metabolic system(s) in the cytoplasm to form interstrand DNA-DNA cross-links, and induces cytotoxicity against the cells. This activation of FK973 in the cytoplasm is discussed in connection with the drug-metabolic system(s) in relation to the structures of the compounds. PMID- 2214371 TI - Effects of intracerebroventricular administration of magnesium sulphate on blood pressure and heart rate in anesthetized normotensive and hypertensive rats. AB - Intracerebroventricular (i.c.v.) injection of magnesium sulphate (MgSO4:2.5, 5 and 10 mumol in 5 microliters) decreased blood pressure and heart rate in both anesthetized normotensive (WKY) and hypertensive rats (SHR). The effects were greater in WKY than in SHR. Moreover, a pretreatment with hexamethonium (2 mg/kg, i.v.) significantly blunted the hypotensive and bradycardic effects induced by i.c.v. injection of 10 mumol of MgSO4 in both WKY and SHR. Our data suggest that MgSO4 produces hypotensive and bradycardic effects when injected i.c.v. in both WKY and SHR. PMID- 2214372 TI - Effects of antihypertensive drugs on experimental cerebral ischemia in spontaneously hypertensive rats. AB - The effects of antihypertensive drugs on ischemic cerebral damage were investigated using the bilateral carotid artery occlusion (BCAO) model in SHR. Oral budralazine and nifedipine, at doses that increased cerebral blood flow (CBF) in SHR in our previous study (Tanaka, S. et al., Folia Pharmacol, Japan, 87, 1986), significantly improved cerebral energy failure after the BCAO, but prazosin which does not increase CBF had no effect on the energy failure. These results suggest that the amelioration by these antihypertensive drugs of the energy failure after the BCAO results from its CBF-increasing effects in SHR. PMID- 2214373 TI - Inhibitory modulation of the reflex tracheal constriction induced by afferent vagal stimulation. AB - Afferent cervical vagal electrical stimulation caused a reflex tracheal constriction. Atropine changed the tracheal constriction into a tracheal dilatation that was almost inhibited by propranolol. In the hypertonic trachea with 5-hydroxytryptamine, a reflex dilatation following a constriction was observed by afferent vagal stimulation. The reflex dilatation was inhibited about 50% by propranolol and was abolished by hexamethonium. These results suggest that the adrenergic and nonadrenergic inhibitory innervations may mediate the reflex tracheal dilatation, especially in a hypertonic tracheal condition. PMID- 2214374 TI - Reduced erythrocyte deformability in anemic rats with adjuvant arthritis. AB - Erythrocytes in anemic rats with adjuvant arthritis (AA) were less deformable compared with normal rats. Swelling of the spleen was noticed in anemic rats with AA. The treatment of anemic rats with recombinant human erythropoietin (r-HuEPO; 30 and 100 U/kg, i.v., for 5 days) resulted in a normalization of both the anemia and erythrocyte deformability. It is suggested that erythrocytes with reduced deformability may be sequestered by endothelial slits of the spleen, which may play a causative role in the anemia in rats with AA. PMID- 2214375 TI - Dissociation between sympathetic purinergic response and ATP response in the mesenteric artery of the dog. AB - In the presence of prazosin and propranolol, electrical transmural stimulation of isolated dog mesenteric artery produced a sympathetic purinergic contraction, which was followed by a relaxation in PGF2 alpha-contracted arteries. Such purinergic responses were mimicked by brief exposure to alpha, beta-methylene ATP (alpha, beta-Me ATP) and were completely inhibited after desensitization of P2x purinergic receptors. However, exogenous ATP predominantly evoked a relaxation in PGF2 alpha-contracted artery. These results suggest that the sympathetic purinergic response may be caused by a P2x-purinergic receptor-selective mechanism or substance, rather than ATP. PMID- 2214376 TI - Greater contraction is induced by pilocarpine than by carbachol at the same levels of cytosolic Ca2+ concentration in isolated longitudinal muscle of guinea pig ileum. AB - Pilocarpine, which activates propylbenzilylcholine mustard (PrBCM)-sensitive cholinoceptors, and carbachol, which activates PrBCM-resistant ones, induced an increase in cytosolic Ca2+ concentration ([Ca2+]i) and tension development in a concentration dependent manner in isolated longitudinal muscle of guinea pig ileum. A positive correlation between [Ca2+]i and tension development due to both of the agonists was noted. The slope of regression line between two values for pilocarpine was steeper than that for carbachol, suggesting that pilocarpine induced carbachol. Thus an activation of PrBCM-sensitive cholinoceptors might enhance the Ca2(+)-sensitivity of the contractile elements. PMID- 2214377 TI - [General concepts and the history of chronic obstructive pulmonary disease]. AB - There is no general agreement on the concepts of chronic obstructive pulmonary disease (COPD) yet in Japan, although there have been significant advances in the understanding of its concepts in the United States and Europe. The purpose of this presentation as the opening remark to this panel discussion is to review the concepts and history of chronic obstructive pulmonary disease (Tables 1, 2), and also to summarize the general concepts concerning COPD in Japan at present. More than 30 years ago, a Ciba Guest symposium first proposed the main subdivisions of chronic non-specific lung disease (CNSLD), consisting of chronic bronchitis and generalized obstructive lung disease (GOLD). Many papers addressed this theme focusing on the definition and concepts of COPD for a long period after the Ciba Guest Symposium. The ATS and ACCP joint committee on pulmonary nomenclature (1975) reported that the term of COPD refers to diseases of uncertain etiology characterized by persistent slowing of airflow during forced expiration, and the committee recommended that chronic obstructive bronchitis or chronic obstructive emphysema be used, whenever possible. However, in many patients it is still difficult determine what extent the airway obstruction result from emphysema and to what extent it results from an accompanying chronic obstructive bronchitis, as Burrows described. Fishman (1980) and Burrows (1981) suggested that if the patient is thought to have a combination of chronic obstructive bronchitis and pulmonary emphysema, the case should be so diagnosed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214378 TI - [The relationship between alveolar apertures and alveolar size and smoking history in humans, and experimental studies on air pollutants]. AB - Using surgical specimens from patients with lung tumor, alveolar apertures and alveolar sizes were quantitatively assessed using scanning electron microscopy. Compared with smoking habits, increased apertures, defined as alveolar destruction were observed in patients smoking more than 35 years, whereas alveolar size was increased in patients, with a 15-year smoking history. Experimental studies with exposure to NO2, O3 and H2SO4 mist showed that exposure of NO2 and H2SO4 could induce epithelial injury such as disappearance of cilia in the central airways. PMID- 2214379 TI - [Comparison of immunological aspects in diffuse panbronchiolitis and cystic bronchiectasis]. AB - We examined immunological parameters in 35 patients with diffuse panbronchiolitis (DPB) and 20 patients with cystic bronchiectasis (CBE) to analyze the relation between local immune responses and subsequent clinical courses. Patients with DPB showed more impaired cell-mediated immunity than those with CBE. On analysis of peripheral blood lymphocytes from DPB and CBE, the significant increase in CD4 positive T-cells and Fc alpha R positive T-cells and decrease in Leu-11 positive cells were recognized. The observation of humoral immunity revealed a tendency for local immunity to be accelerated such as increases of IgA and IgG2 in both diseases. The titer of serum cold agglutinin and rheumatoid factor were elevated in DPB. However, these fluctuations of immunological factors were normalized according to improvement of inflammatory processes by chemotherapy. The analysis of the distribution of lymphocyte subsets in lung tissues taken from DPB showed that CD4 positive T-cells always overwhelmed CD8-positive T-cells and that secretary IgA-positive B-cells were abundant in bronchioles. On the other hand, bronchiolitis was recognized in about 80% of cases with CBE, although to a less striking degree than DPB. Lymphocyte subsets were similarly distributed in the respiratory tract. DPB and CBE could be considered as the same disease entity in the spectrum of chronic respiratory tract infection based on mucociliary disorder. Sinusitis and immunological abnormalities are often complicated by both diseases. However, precise analysis demonstrated that there are some obvious differences of systemic and local immune responses between DPB and CBE, probably due to the conditions of each diseases such as primary focus, severity and causative microorganism. PMID- 2214380 TI - [Chronic bronchitis and related disorders]. AB - Chronic bronchitis was a disease which attracted much attention in the U.K. in the 1950's. It was classified into three forms known as simple chronic bronchitis, recurrent or mucopurulent bronchitis, and chronic obstructive bronchitis and it was thought that the disease progressed from one form to the next in accordance with their order as listed here. Later, however, it was realized that the disease did not progress according to this order and that chronic bronchitis actually included three kinds of the disease. Furthermore, in the U.K., with the prohibition of the use of coal and the reduction of air pollution and with the decline of infectious disease in child age, recurrent or mucopurulent bronchitis underwent an extreme reduction. Chronic obstructive bronchitis is known to be caused by smoking and is now called chronic bronchitis and emphysema or COPD. Simple chronic bronchitis may in fact be only a simple physical response to smoking. Now in Japan the disease called chronic bronchitis is often recognized when written on receipts for health insurance, but patients of chronic bronchitis as were seen in the U.K. in the 1950's are extremely rare. Diffuse panbronchiolitis is seen in Japan but is a disease not found in the West. Diffuse bronchiectasis and its differentiation become the point of question for this disease. With the effectiveness of erythromycin, we can expect a decline in the number of patients and an improvement in prognosis. PMID- 2214381 TI - [The epidemiology of obstructive lung diseases]. PMID- 2214382 TI - [Evaluation of diffuse lung uptake of 201Tl in bronchopulmonary diseases]. AB - 201Tl scintigraphy was performed in various bronchopulmonary diseases. Applying semiquantitative and visual assessments of grade of 201Tl was observed in various broncho-pulmonary diseases with multiple or numerous abnormal shadows in the lung fields, and obvious lung uptake was also shown even in some cases with few or no abnormal shadows. Positive results of moderate and marked lung uptake of 201Tl more than 60.0% were obtained in diffuse interstitial pneumonia, hypersensitivity pneumonitis, silicosis, the disseminated type of pulmonary tuberculosis and primary lung cancer. The ratio of radioactivity of the lung (maximum) to the upper mediastinum was 1.04 +/- 0.24 in healthy controls, and more than 2.0 in diffuse interstitial pneumonia, hypersensitivity pneumonitis and silicosis. The ratio of radioactivity of the right lung to the administered dose of 201Tl was 1.5 +/- 0.9% in healthy controls, and more than 3.0% in diffuse interstitial pneumonia, silicosis, the disseminated type of pulmonary tuberculosis and primary lung cancer. Lung uptake of 201Tl was diffuse, homogeneous and marked in diffuse interstitial pneumonia and hypersensitivity pneumonitis, while it was scattered and slight in chronic obstructive lung diseases. 201Tl scintigraphy seems to be useful for detecting interstitial disorders of the lung including edema, inflammatory and granulomatous changes, especially in cases with slightly abnormal or normal chest X-ray films. PMID- 2214383 TI - [Correlation between slopes of pulmonary blood flow-driving pressure curve and routine pulmonary function]. AB - In 91 preoperative cases of lung cancer, an attempt was made to correlate the slopes of pulmonary blood flow-driving pressure curve (delta DP/delta CI), as constructed from unilateral pulmonary arterial occlusion (UPAO) test values and pulmonary blood flow fraction values as measured by scintigraphy, with total pulmonary vascular resistance index (TPVRI) and pulmonary vascular resistance index (PVRI) and routine pulmonary function. FVC and FEV per unit body surface (BSA) were found to correlate, to same degree, with delta DP/delta CI, TPVRI and PVRI (p less than 0.05). delta DP/delta CI correlated significantly with FRC/BSA, whereas TPVRI and PVRI did not. 3) The inverse of the cardiac index (1/cardiac index) was shown to significantly correlate with TPVRI and PVRI (r = 0.64, 0.48), but poorly with delta DP/delta CI (r = 0.32). These results suggest that delta DP/delta CI might possibly provide a more useful quantitative index for the pulmonary vascular bed than TPVRI and PVRI. PMID- 2214384 TI - [Treatment of spontaneous pneumothorax by electrocoagulation via a fiberoptic bronchoscope with a hysteroscope irrigation outer sheath as a thoracoscope]. AB - Since 1981 in Yamagata Prefectural Central Hospital, the authors performed electro-coagulation therapy for air leakage from bullae (blebs) via a rigid thoracoscope in 31 patients with spontaneous pneumothorax. Among these patients, this treatment was unsuccessful in 14 patients (45.2%) because of 5 multiple or giant bullae and 9 cases in which it was impossible to visualize the bullae in the mediastinum or because of pleural adhesion. In order to widen the visual field and increase the mobility of the thoracoscope, we employed a fiberoptic bronchoscope with a hysteroscope outer sheath used for irrigation as a flexible thoracoscope. This method makes it possible to examine both mediastinal pleura and adhesive pleural space, and to electrocoagulate bullae which cannot be visualized by a rigid thoracoscope. It was possible to visualize the blebs in all 13 cases with spontaneous pneumothorax in which this examination was attempted. This therapeutic procedure causes the patients less pain and the hospitals more economical because no new thoracoscope is necessary. This method of thoracoscopic therapy of spontaneous pneumothorax using a fiberoptic bronchoscope is more successful, effective, economical and painless than by rigid thoracoscope and should be attempted before thoracotomy. PMID- 2214385 TI - [The role of chemotactic factors in the pathogenesis of sarcoid granuloma formation]. AB - There is evidence suggesting that macrophages and epithelioid cells, predominant cells in sarcoid granuloma, are derived from circulating monocytes on a gradient of chemotactic factors between the lesion and the circulation. A previous study by the author showed that epithelioid cells and lymphocytes from sarcoid granulomas released chemotactic factors to attract blood-derived mononuclear cells. The present study was undertaken to further explore the role of chemotactic factors in the pathogenesis of sarcoid granuloma formation. Twenty two sarcoid patients, 14 patients with active pulmonary involvement and 8 patients without pulmonary involvement, were lavaged and the bronchoalveolar lavage (BAL) fluids were evaluated for chemotactic activity. Chemotactic activity was detected in BAL fluid from sarcoid patients with active pulmonary disease, but not from those without pulmonary involvement. Chemotactic activity for mononuclear cells in the BAL fluid correlated with the percentage of lymphocyte numbers (r = 0.702, p less than 0.05) and number of CD4+ lymphocytes (r = 0.796 p less than 0.02) present in the BAL fluids, which has been proved to reflect disease activity. Chemotactic activity was independent of the amounts of albumin in BAI fluid (r = 0.271, p less than 0.10). Chemotactic factors in BAL fluid were eluted in 4 different regions on molecular sieving and were stable at 56 degrees C for 30 min. However, chemotactic activities were abolished completely by treatment at 100 degrees C for 30 min or trypsinization. Our observations suggest that chemotactic activity in BAL fluid from sarcoid patients reflects the disease activity contributing to formation of sarcoid granulomas. PMID- 2214386 TI - [Nutritional assessment of chronic pulmonary emphysema and the significant relation of malnutrition to pulmonary function and respiratory muscle function]. AB - We assessed nutritional status in 30 patients with pulmonary emphysema and 60 healthy controls. The relationship between nutritional status, pulmonary function and respiratory muscle function was also studied. Anthropometric measures, visceral proteins such as PA and RPB, and the Fischer ratio (BCAA/AAA), an index of imbalance of amino acids were significantly lower in the patients. The incidence of moderately malnourished patients with less than 80% of IBW was 40%. The incidence of hyporetinol-binding protein was 40%. 48% of the patients were found to show an amino acid imbalance. These findings suggested that protein energy malnutrition in association with amino acid imbalance occurred commonly in patients with pulmonary emphysema. FEV1% correlated significantly with some anthropometric indices and the Fischer ratio. Respiratory muscle function, assessed by P1 max, correlated significantly with some anthropometric indices and grasp strength. These results suggested that the degree of airway obstruction and respiratory muscle function was associated with malnutrition characterized by the reduction of the Fischer ratio. PMID- 2214387 TI - [Ferruginous bodies in the lungs of the general population during a 45-year period and mineralogical examination]. AB - In order to determine the level of asbestos pollution in the lungs of members of the general population in and around Tokyo, the incidence of ferruginous bodies in autopsied or resected lungs during 5 periods over the 45 years from 1937 to 1981 was studied by a light microscopy. Core fibres, after removal of their ferruginous coatings with oxalic acid, and uncoated fibres were analyzed using a scanning electron microscope equipped with a Kevex energy-dispersive X-ray spectrometer. The incidence of ferruginous bodies in 5 g (wet) of digested lung tissue was shown to be 10% in period I (1937-1941), 18% in period II (1947-1951), 70% in period III (1958-1963), 74.4% in period IV (1970-1973) and 81.0% in period V (1980-1981). The major types of core fibres of ferruginous bodies were found to be asbestos, including amosite, crocidolite, chrysotile and the tremolite actiolite series, but a small number of fibers of materials other than asbestos were also detected. In contrast, a large number of short fibers less than 5 microns in length in 1 g of wet lung tissue were classified as belonging to Mg + Si fibers (the ratio of Mg to Si components being 30% or over) and presumed to be chrysotile. Thus an annual increase in asbestos deposition in lungs of people living in and around Tokyo has been demonstrated and fine chrysotile fibers less than 5 microns in length seem to be the main type of deposited fibers. PMID- 2214388 TI - [Foreign body-induced bronchial actinomycosis with severe stenosis that must be distinguished from lung cancer]. AB - A 59-year-old woman who accidentally swallowed a foreign body (fish bone) 9 months ago was admitted to our hospital because of cough, hemosputum and sleep wheezing for two months. Chest roentgenograms and chest CT scanning revealed severe stenosis of the right lower lobe bronchus and truncus intermedius, suggesting lung cancer. Bronchoscopic examination revealed an intrabronchial foreign body. The biopsy specimen from granulation tissue revealed bronchial actinomycosis. The foreign body was removed bronchoscopically after an extensive chemotherapy with penicillin G (for actinomycosis) and prednisolone (for granulation tissue of the bronchus). This was considered to be a rare case of bronchial actinomycosis without a pulmonary lesion produced by a foreign body. PMID- 2214389 TI - [A case of adult T-cell leukemia with diffuse panbronchiolitis]. AB - We have reported an adult T-cell leukemia (ATL) patient with a 3-year history of diffuse panbronchiolitis (DPB). The patient, a 62-year-old woman, had been complaining severe cough and purulent sputa for 2 years. In 1984, she was admitted to Saga Medical School, where her clinical diagnosis, DPB, was made. One year later, it was revealed that she suffered from ATL, confirmed by the presence of ATL cells in peripheral blood and anti-ATLA antibody. This case suggests that ATL may play an important role in the pathogenesis of some DPB patients. PMID- 2214390 TI - [A case of bronchiolitis obliterans organizing pneumonia in a patient with rheumatoid arthritis]. AB - A 54-year-old man with rheumatoid arthritis visited his general practitioner because of fever and cough. Chest X-ray showed an infiltrative shadow in the right lower field. Antibiotic treatment was not effective, and the specimens obtained by transbronchial lung biopsy was not diagnostic. The patient was transferred to our hospital for further examination and treatment. Previously he had been treated with prednisolone in the knee joint for rheumatoid arthritis. Open lung biopsy was performed. The specimen obtained showed bronchiolitis obliterans organizing pneumonia (BOOP) histologically. The patient recuperated and the chest X-ray shadow decreased with no therapy except the previous treatment with prednisolone. PMID- 2214391 TI - [A case report of mediastinal malignant lymphoma with long survival following combination chemotherapy using adriamycin, vincristine and cyclophosphamide]. AB - Mediastinal B-cell malignant lymphoma of a 22-year-old female was successfully treated by combination chemotherapy including Adriamycin, Vincristine and Cyclophosphamide. She suffered from dyspnea and axillary tumor in September 1984. Roentgenological examination revealed a large anterior mediastinal tumor. Biopsy of the axillary tumor yielded a diagnosis of metastatic undifferentiated carcinoma from thymus by hematoxylin and eosin. Radiotherapy and chemotherapy including CDDP and ACNU resulted in a symptom-free period of only 2 months. Superior vena cava syndrome and massive pleural effusion recurred. Salvage chemotherapy including Adriamycin, Vincristine and Cyclophosphamide resulted in rapid therapeutic effect. Six courses of chemotherapy were administered, and she is alive and well 4 years after the first salvage chemotherapy. A definitive diagnosis of B-cell lymphoma was made after review of biopsy specimens using immunohistochemical procedures. To select adequate treatment for mediastinal malignant lymphoma, reliable diagnostic procedures including immunohistochemistry are needed. Intensive chemotherapy with appropriate drugs may obtain good response even in advanced cases, such as this. PMID- 2214392 TI - [A case of essential thrombocythemia with pulmonary hypertension and bilateral pleural effusions]. AB - A 79-year-old woman was admitted with general fatigue. Chest roentgenogram showed diffuse reticular shadows and bilateral pleural effusion. Peripheral blood studies revealed an elevation of platelet count (203.3 X 104/mm3). The case was diagnosed as essential thrombocythemia and treated with ACNU. The platelet count decreased. Bilateral pleural effusions increased gradually and their characteristics changed from bloody exudate to transudate. Biopsy of her pleura and thoracoscopy were carried out without significant results. Later, systemic edema, which suggested right heart failure, developed. The diagnosis of pulmonary hypertension and right heart failure was made by echocardiogram and right cardiac catheterization. Because perfusion scan of the lung revealed some perfusion defects, complication of pulmonary embolism was suspected. Bilateral pleural effusion and pulmonary artery pressure decreased with treatment by nifedipine, furosemide and isosorbide dinitrate. This is the first case report of essential thrombocythemia, pulmonary hypertension, right heart failure and bilateral pleural effusion. PMID- 2214393 TI - [Second serogroup of Legionella pneumophila isolated from a patient with fulminant pneumonia]. AB - A 67-year-old female was admitted to our hospital, because of high fever and dry cough. She had undergone semiradical hysterectomy and radiation therapy for carcinoma of the uterine cervix one year previously. Her chest roentgenograms on admission showed lobar consolidation of the left upper lobe. Antibiotics were administered but her general condition and pulmonary consolidation did not improve. As Legionellosis was highly suspected, we performed bronchoscopic examinations. Bronchial mucosa was almost normal with no secretion, and Legionella was isolated from the specimen obtained bronchoscopically. Six days later, L. pneumophila serogroup 2 was isolated and identified from an intratracheal aspiration, and serological diagnosis was made by indirect immunofluorescence antibody. We could also detect the bacteria in the BALF by immunofluorescence microscopy and in the tissue of the TBLB specimen with the ABC method. PMID- 2214394 TI - [A case report of endobronchial lipoma]. AB - Endobronchial lipomas are rare benign tumors of the lung. Nineteen cases have been reported in Japan. We present a case of endobronchial lipoma obstructing the left B4b and chronic saccular bronchiectasis throughout the left upper lobe. A 42 year-old man, 174 cm tall and weighing 47 kg, was referred for investigation of an abnormal chest X-ray film. He had a history of pneumonia and pyothorax in infancy. The chest X-ray film showed linear densities and ill-defined, irregular opacities in the upper-middle lung field. CT scan and tomographic studies showed multiple cystic spaces in the left upper lobe in which the volume was diminished. An angiogram of the left bronchial artery showed peripheral hypervascularity in the left upper lobe and systemic-to-pulmonary artery shunt. Fiberoptic bronchoscopy revealed a smooth, pink mass obstructing B4b. Biopsy specimens were insufficient for histological diagnosis. Preoperatively, an inflammatory polyp in association with chronic saccular bronchiectasis was suspected. Left upper lobectomy was performed on January 13, 1989. Gross examination of the resected specimen showed a pedunculated polypoid mass, 1.5 X 1.2 X 0.6 cm, attached to the bronchial mucosa of B4bii and saccular ectatic changes of bronchi not only in the lingular division but also in upper division. Microscopically, the endobronchial tumor consisted of mature adipose tissue covered with columnar bronchial epithelium. The fat was fairly well localized in the submucosa, but was not encapsulated and did not enclose glands or smooth muscle fibers. The endobronchial lipoma was thought to originate in the bronchus of chronic saccular bronchiectasis. PMID- 2214395 TI - [A case of plasma cell granuloma showing rapid growth and elevation of serum CEA]. AB - A 67-year-old man was admitted with complaints of cough and hemosputum. Chest X ray examination revealed enlargement of a coin lesion in the right upper lobe, which had been pointed out about one year previously and had been followed up. Although the histology of TBLB specimens and the cytology of sputum and materials showed no malignancy and chest CT showed calcification at the edge of the coin lesion, the mass shadow in the right upper lobe rapidly enlarged and the serum level of CEA gradually elevated. Therefore, it seemed to be impossible to neglect the possibility of lung cancer and right upper lobectomy was performed. The dissected specimen was diagnosed as plasma cell granuloma. Because the histology of the plasma cell granuloma is multifarious, TBLB shows various results. It is therefore difficult to diagnose such inflammatory tumors by TBLB. The increase of the mass shadow in size and the elevated serum level of CEA made it difficult to diagnose this case. PMID- 2214396 TI - [A case of invasive thymoma displaying endobronchial polypoid growth]. AB - A 58-year-old woman was admitted due to an abnormal shadow on chest X-ray film and two episodes of hemoptysis during the past two years. Chest radiography showed a mass with calcification in the left upper lobe of the lung. A white polypoid lesion in left B3b + c bronchus was discovered by fiberoptic bronchoscopy. Biopsy specimen of the polypoid lesion demonstrated fungi like aspergilli in the necrotic tissue. We suspected pulmonary aspergillosis combined with old tuberculosis and treated with antifungal and antituberculous drugs. After nine months, however, we recognized that the mass had become larger radiologically. A polypoid tumor with a brown, glossy surface in the left B3 bronchus was again noted endoscopically. Histologic findings of the biopsy specimen obtained from this tumor were suggestive of thymoma. Thymectomy and left upper lobectomy were performed. The cross-section of the surgical specimen revealed that the tumor extended not only in the mediastinum but also in the pulmonary parenchyma with polypoid growth into the lumina of bronchi. Microscopically, the tumor was an invasive thymoma composed of both epithelial and lymphocytic elements. PMID- 2214397 TI - [A case report of psittacosis and chlamydial isolation from a dead pet bird]. AB - A 33-year-old previously healthy woman was seen at this hospital after a week of fever and nonproductive cough. A roentgenogram of the chest showed consolidation in the left upper and middle lung fields. Transbronchial lung biopsy from left S1 + 2 revealed an increase of mononuclear leukocytes within the interstitial spaces and slight cell infiltration with in the alveoli. Bronchoalveolar lavage cellular constituents showed 47% alveolar macrophage, 38% lymphocytes and 15% neutrophils. She had kept a parakeet, which died just after her illness. We could isolated organisms from the liver, spleen, kidney, lung, heart and bowel of her pet bird revealing C. psittaci by Giemsa stain, three days after it was buried in the ground. She was given three hundred mg of ofloxacin per day orally for fourteen days and the clinical effect was good. The in vitro activity of ofloxacin was 0.75 microgram/ml. PMID- 2214398 TI - [Bronchiectasis with normal paranasal sinus roentgenogram]. AB - Bronchiectasis has come to be considered as a type of sinobronchial syndrome in Japan, but there exist some cases without chronic sinusitis. We studied the clinical features of 14 cases of bronchiectasis with definitely normal paranasal sinus roentgenogram, diagnosed during the past ten years. There were eleven middle-aged women and three men. Ten patients (71%) complained of hemoptysis, one (7%) of dry cough, one (7%) of productive cough, and the two (14%) had no complaint. In seven patients (50%) CT and bronchography showed localized cylindrical bronchiectasis in the right middle lobe and/or left upper lobe lingular division. They were considered to be middle lobe lingular syndrome. Three patients (22%) with localized varicose or cystic bronchiectasis had a history of pneumonia or pertussis in their infancy, so their bronchiectasis were considered secondary to infantile bronchopulmonary disease. Two patients (14%) had diffuse cystic bronchiectasis and were almost asymptomatic. They might be cases congenital bronchiectasis or Williams-Campbell syndrome. Pulmonary function tests were normal in most of the cases and sputum culture revealed no cases of persistent bacterial infection. These clinical features are quite different from those of bronchiectasis reported as sinobronchial syndrome, in which chronic productive cough, poor pulmonary function, persistent bacterial infection, etc. are significant. So we conclude that there are two distinct groups in bronchiectasis. PMID- 2214399 TI - [Membranous and respiratory bronchiole disease in patients with normal air-flow and mild air-flow limitation]. AB - In order to evaluate the role of membranous (MB) and respiratory bronchioles (RB) in patients with normal and mild airflow limitation, we quantitatively assessed the pathological change of MB, RB and alveoli in the pathological specimens of 42 patients who required surgery for removal of a solitary pulmonary nodule. We also measured the destructive index (DI), to evaluate the destruction of alveolar walls. High resolution CT scan and pulmonary function tests were performed within 1 month of resection. Results of the pulmonary function tests correlated with pathological changes of RB better than with MB. Significant correlation between the emphysema score of resected lung and the pathological change of MB and RB was observed. There was also significant correlations between the CT score or DI and RB changes. However, there was no significant correlation between the CT score or DI and the change of MB. There were significant differences between smokers and nonsmokers in the results of pulmonary function test, pathological changes of RB and severity of emphysema. We postulate that RB is responsible for subtle functional abnormalities in the early stages of chronic obstructive pulmonary disease. PMID- 2214400 TI - [Airway occlusion pressure during sleep in normal subjects]. AB - Sleep has been shown to be associated with a variety of changes in ventilatory mechanics. Recently, airway occlusion pressure (P0.1) has come to be widely used as an index of the neural output of the respiratory center, and is considered to be independent of lung mechanics. The purpose of this study was to analyze neural output of the respiratory center during sleep, utilizing an airway occlusion pressure procedure. Nine normal male subjects, 19 to 32 yrs of age, were used. Each subject was fitted with a face mask, and the area between the mask and the face was sealed with medical silicone rubber. They breathed through the mask, which was attached to a "J" valve that separated the inspiratory from the expiratory line. A radio-controlled camera shutter was joined to the "J" valve on the inspiratory line. The volume of dead space of this system was about 150 ml. Inspiratory pressure developing in the oral cavity was measured using a pressure transducer and a photocorder. Flow rate, tidal volume (VT) and inspiratory time (TI) were measured using a hot wire flow meter. Airway occlusion pressure (P0.1) was measured 0.1 second after the onset of the inspiratory effort by occluding the shutter on the inspiratory line during expiration. The onset of inspiration and expiration was detected by changes in airway pressure. Great care was taken to make the subjects as comfortable as possible during the procedure. Continuous recordings were made on a polygraph recorder of EEG, EOG, EMG and cardiorespiratory variables. Sleep stages were determined using the standard criteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214401 TI - [Variety of neutrophil chemotactic factors in the respiratory tracts in patients with respiratory diseases]. AB - We measured NCF activity and examined the characteristics of NCF in bronchoalveolar lavage (BAL) fluid, sputum and culture media of alveolar macrophages. Several kinds of NCF were detected in BAL fluid obtained from normal volunteers, and at least a part of these NCF was thought to be derived from alveolar macrophages. NCF activity, especially complement-derived NCF, was increased in BAL fluid and in sputum obtained from patients with chronic respiratory tract infection. In patients with idiopathic interstitial pneumonia, alveolar macrophage-derived NCF as well as complement derived NCF were increased in BAL fluid. These results indicate that different types of NCF may increase in response to the disease state or pathogenesis, and play important roles in neutrophil accumulation in the respiratory tract. PMID- 2214402 TI - [Lung surfactant apoprotein (LSP) content of sputum samples from patients with chronic airway diseases]. AB - LSP contents of sputum samples from patients with chronic airway diseases were measured by an enzyme-linked immunosorbent assay (ELISA) kit which was designed by Kuroki et al to examine whether a substance identical to lung surfactant contained in alveolar lining layer, is also contained in respiratory tract fluid or not in the ELISA kit. One antibody to LSP was conjugated to peroxidase and another one to LSP was fixed onto a bead. A neo-anionic detergent, Triton X-100 and an anionic detergent, sodium dodecyl sulfate (SDS) were added to extraction medium to separate LSP from lung surfactant, and LSP reaction of sputum sample was maximal when the ratio of Triton X-100 to SDS was in range of 1 to 4. Airway mucous glycoprotein (AMG) purified from sputum sample did not show any LSP reaction. In CsCl density gradient ultracentrifugation of whole sputum, the LSP reaction was detectable only in the top fraction with density of about 1.40 and AMG was located in the fraction with a density of about 1.50. These results indicate that the LSP reaction of sputum sample is not due to false reaction caused by nonspecific binding of viscous AMG to the two antibodies to LSP, but to the existence of LSP. Therefore it was concluded that lung surfactant is contained in respiratory tract fluid. In general, the LSP concentrations in sputum samples were lower in purulent sputa than in mucoid or mucopurulent sputa, and lower in patients with diffuse panbronchiolitis and bronchiectasia than in those with pulmonary emphysema and chronic bronchitis. It was shown that LSP was hydrolyzed by neutrophil leucocyte homogenate. These results suggest that LSP content of sputum is influenced by various factors such as infection and disease in the respiratory tract, and thus is useful to estimate pathological states of chronic airway diseases. PMID- 2214403 TI - [A case report of high plasma renin activity in chronic pulmonary disease and the effect of angiotensin-II-analogue (1-sarcosine, 8-isoleucine-angiotensin-II)]. AB - Five patients with chronic pulmonary diseases (3 pulmonary emphysema, 1 chronic respiratory failure caused by old tuberculosis, 1 diffuse panbronchiolitis) showed a marked increase of plasma angiotensin-I and PRA level, which was accompanied by an increase of angiotensin-II level, however, whose systemic blood pressure was not elevated. The intravenous infusion of angiotensin-II-analogue (1 Sarcosine, 8-Isoleucine-Angiotensin-II) elicited an antagonistic blood pressure response resembling Bartter's syndrome. PMID- 2214404 TI - [Significance of superior vena cava reconstruction with EPTFE grafts in the surgical treatment of superior and anterior mediastinal invasive malignant tumors]. AB - The objective of this study is to demonstrate the significance of superior vena cava (SVC) reconstruction in the surgical treatment of superior and anterior mediastinal invasive malignant tumors, by using a total of 48 cases consisting of 36 invasive thymomas, 3 thymic cancers, 3 carcinoids, 2 germ cell tumors, 2 malignant lymphomas, 1 intrathoracic thyroid cancer and 1 malignant melanoma. In 22 of 48 cases there was only mediastinal pleural invasion or tumor capsule invasion, on the other hand, 26 cases had high ratios of invasion to adjacent organs, including lung, pericardium, great veins and the phrenic nerve. Sixteen of 26 cases had invasion to 1-2 adjacent organs, but 10 had 3-6 organ invasion. Among 12 cases invading SVC or brachiocephalic veins, 9 cases during the last 7 years underwent SVC resection and reconstruction with EPTFE grafts. The patency was good in the grafts with external ring support and no SVC symptoms were observed in all cases postoperatively. The longest patent and functional graft is 40 months postoperative. No statistically significant difference were demonstrated in the survivals between cases with SVC reconstruction and those with resections of other adjacent organs, furthermore, remarkable difference of survival was demonstrated in SVC reconstructed cases with complete resection and incomplete resection. The survivals in cases with combined resection of 1-2 adjacent organs was statistically significantly better than those with combined resection of 3-6 adjacent organs (p less than 0.05, Cox-Mantel test).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214405 TI - [Double filtration plasmapheresis in case of Goodpasture's syndrome]. AB - This article describes a case of Goodpasture's syndrome controlled by double filtration plasmapheresis (DFPP) combined with steroid and immunosuppressant therapy. A 48-year-old male, clerk, complaining of fever, dry cough and macroscopic hematuria, was admitted to our hospital. Microscopic hematuria was first pointed out at age 40 on an annual check up. His laboratory data on admission revealed severe anemia, azothemia, macroscopic hematuria and proteinuria. His chest radiograph and CT revealed diffuse nodular densities in bilateral lung fields. Specimens obtained by transbronchial lung biopsy and open renal biopsy revealed linear deposition of IgG by direct immunofluorescent antibody methods. Circulating antiglomerular basement membrane antibody level determined with radioimmunoassay was 1.8% on admission, but one week later it elevated to 5.6% with progression of dyspnea, hypoxemia, and renal failure. Steroid pulse therapy and a total of 6 double filtration plasmaphereses were performed in the first month. Subsequently hypoxemia and dyspnea disappeared, and the chest radiograph of the 40th hospital day showed no abnormal shadows. Two months later recurrence of pulmonary hemorrhage was noticed. Immunosuppressant administration (Cyclophosphamide 100 mg/day) and a total of 10 DFPP procedures were performed with success. By DFPP, circulating anti-GBM antibody fell rapidly to within normal ranges, and anti-GBM antibody level elevated in removed plasma. We think DFPP is effective to remove circulating anti-GBM antibody in Goodpasture's syndrome. PMID- 2214406 TI - [A case of Goodpasture's syndrome with IgA antibasement membrane antibody]. AB - This is a very rare case report of Goodpasture's syndrome with IgA antibasement membrane antibody. A 43-year old male was admitted because of severe dyspnea with slight hemoptysis. Chest X-ray demonstrated extensive bilateral infiltrates with air bronchogram, predominantly in the right lung. Laboratory data on admission showed severe anemia and moderate renal impairment. The pulmonary infiltrates resolved spontaneously within 10 days. Goodpasture's syndrome or collagen vascular disease was suspected and he underwent a percutaneous renal and transbronchial lung biopsy. The renal biopsy showed crescent formation affecting 70-80% of glomeruli. Linear IgA deposits, but not IgG, were demonstrated along the glomerular basement membrane by the direct immunofluorescence procedure. The lung biopsy contained many hemosiderin-laden macrophages in the lumen of the alveoli and showed mild thickening of alveolar walls. However, linear immunoglobulin deposits on the alveolar capillary basement membrane were not demonstrated by direct immunofluorescence. The diagnosis of Goodpasture's syndrome with IgA antibasement membrane antibody was made. His serum was negative for antibasement antibody by indirect immunofluorescence. He was treated with prednisone, 30 mg daily. His pulmonary symptoms and anemia improved markedly, but his renal function did not change. Thirteen months after his first admission, he suffered from severe bacterial pneumonia, which was complicated by disseminated intravascular coagulation. He died of respiratory failure. Autopsy was rejected. PMID- 2214407 TI - [A case of Pryce's type I intralobar pulmonary sequestration diagnosed by noninvasive techniques]. AB - The patient was a female who came to our hospital with a chief complaint of hemoptysis. Radiography of the chest demonstrated a funicular shadow, and CT of the chest also revealed a similar shadow in contact with the thoracic aorta enhanced by the contrast material. Pulmonary arteriography and aortography showed that the left S8, S9 and S10 areas were supplied by abnormal blood vessels bifurcating from the thoracic aorta, rather than the pulmonary artery. This finding was supported by scintigraphy of the pulmonary blood flow and pulmonary RI angiography. Since bronchography revealed no obvious abnormality in the bronchial system, the diagnosis of Pryce's type I intralobar pulmonary sequestration was established, and left lower lobectomy was carried out. While the evidence of abnormal blood vessels is important for the definitive diagnosis of pulmonary sequestration, concurrent image processing of the results of scintigraphy of the pulmonary blood flow and pulmonary RI angiography permits noninvasive demonstration of the fact that the sequestral pulmonary tissue is regulated by the systemic circulatory system, rather than the pulmonary circulatory system and thus is a useful technique. PMID- 2214408 TI - [A case of desquamative interstitial pneumonia (DIP) suggesting a relationship to chronic eosinophilic pneumonia (CEP)]. AB - A 43-year-old man was admitted to our hospital because of cough and dyspnea. His chest X-ray showed bilateral basal infiltrative shadows. The increased eosinophils in BAL suggested chronic eosinophilic pneumonia (CEP), whereas the TBLB specimens showed findings compatible with desquamative interstitial pneumonia (DIP). The open lung biopsy specimens showed typical findings of DIP with a peripheral zone, suggestive of CEP. These two diseases may be only phasal differences of reaction to the same extrinsic stimulation. PMID- 2214409 TI - [A case of pulmonary nocardiosis diagnosed by percutaneous aspiration]. AB - A 71-year-old man complained of mild dyspnea, and his chest X-ray showed a cavitating lesion accompanied by infiltrative changes in the right middle lobe. Percutaneous aspiration revealed numerous gram-positive and acid-fast branching rods. Morphological examination and biochemical tests of the colonies confirmed the diagnosis of pulmonary nocardiosis caused by nocardia asteroides. The patient was treated successfully with sulfamethoxazole-trimethoprim. It has been reported that approximately half of the patients with pulmonary nocardiosis have immunodeficiency, but our patient had no underlying disease. This disease has no characteristic clinical features, so diagnosis is difficult. As nocardia may involve the central nervous system leading to a poor prognosis, early diagnosis and prompt treatment are required to improve survival. PMID- 2214410 TI - [Computed tomographic-pathologic correlation of centriacinar emphysema]. AB - Centriacinar emphysema (CAE) is in principle defined and diagnosed pathologically. However, recently, computed tomography (CT) has been advocated in the diagnosis of emphysema because of the high degree of anatomic details it can provide. In order to assess the reliability and detectionability of CT in CAE detection, as well as evaluation of the severity, a CT-pathologic correlative study of CAE was performed. To study direct one-to-one CT (in vivo)-pathologic correlation, 20 lung lobes with CAE from autopsies and resections were inflated and fixed by the method of Heitzman et al and then sectioned along the plane equivalent to the CT images. The degree of CAE was graded pathologically by the point-counting method. The CT scans were assessed visually for low-attenuation areas by 3 independent physicians. A significant correlation was found between the CT and pathologic scores of the studied lobes (r = 0.94). Detectionability of CAE on lung slices by CT were 74%, 91%, and 100% for mild, moderate, and severe cases respectively. The smallest size of the diameter of emphysematous spaces which could be detected by CT with 10 mm collimation was 3-4 mm. We concluded that CT extremely useful in assessing the extent of CAE, however there are limitation in the diagnosis of mild cases. Moreover, visual scoring of low attenuation areas on CT images was found to be clinically useful in the quantitative evaluation of CAE. PMID- 2214411 TI - [Correlation of CT and pathologic findings of pulmonary lymphangioleiomyomatosis]. AB - The X-ray CT findings of two cases of pulmonary lymphangioleiomyomatosis were reported. The correlation between high-resolution CT findings and inflated biopsy specimens was studied. The X-ray CT findings are 1) multiple low attenuation areas, 2) diffuse areas of slightly increased density and 3) irregular enlargement of pulmonary vascular images. Each low attenuation are turned out to correspond to emphysematous lesions. Slightly increased densities on CT images seemed to be caused by a summation of many small nodules of a proliferation of smooth muscle cells located in the wall of respiratory bronchioles and alveolar ducts, with or without intraalveolar hemosiderosis. Some nodular lesions in bronchiolar walls were so close to neighboring vessels that they could not be separated from vascular images on CT, so peripheral vascular images were irregularly thickened. X-ray CT reflected more actual pathological findings than routine chest radiographs. As low attenuation areas on CT images have been reported to be representative of pulmonary emphysema, it is thought that the above CT findings must be differentiated from those of pulmonary emphysema. While pulmonary vascular images were thin and stretched on the CT in patients with emphysema, they were irregularly thickened on the CT of patients with LAM. Furthermore, while CT of emphysema often revealed overinflation or decreased density, diffuse areas of slightly increased density were never found in emphysema. PMID- 2214412 TI - [The effect of short-term nasal CPAP therapy in cases of obstructive sleep apnea syndrome]. AB - Recent studies have shown that nasal CPAP is very effective in the treatment of patients with obstructive sleep apnea syndrome (OSA). To clarify the characteristics of pulmonary function testing and to evaluate the effect of short term nasal CPAP therapy in 13 cases of OSA patients, nasal CPAP was used for 10 to 14 days and polysonography was performed on two consecutive nights without nasal CPAP and at one night with nasal CPAP. Pulmonary function tests and the Uchida-Kraepelin test were performed before the initiation of nasal CPAP therapy and also 7 to 14 days after the nasal CPAP therapy. Apnea index reduced significantly in all cases from 5.10 +/- 19.6 episodes/hour without therapy to 3.1 +/- 3.5 with nasal CPAP (p less than 0.001). Nasal CPAP significantly reduced the frequency of obstructive (p less than 0.001) and mixed apnea (p less than 0.01), but the frequency of central apnea did not change with nasal CPAP. During the nasal CPAP, mean nadir SaO2 rose from 87.3 +/- 2.9% to 92.7 +/- 1.1% (p less than 0.001) and the lowest SaO2 rose from 73.3 +/- 6.4% to 92.0 +/- 2.1% (p less than 0.001). Before the nasal CPAP therapy, daytime PaO2 was 80.6 +/- 6.4 Torr and closing capacity (CC)/FRC ratio was higher when patients were in a supine than in a sitting position. After short term nasal CPAP therapy, daytime PaO2 increased significantly (p less than 0.001), and FRC/TLC in a supine position increased and CC/FRC in a supine position decreased in some patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214413 TI - [Immunohistochemical analysis of T-lymphocyte subsets on the sarcoid lymph nodes using the computerized analytic system for the light microscopic figures: the relation to the histological maturation stages of the lymph nodes]. AB - Lymph nodes obtained from 19 patients with sarcoidosis were classified into four groups according to their histological maturation stages, which were the early stage, the former mature stage, the late mature stage and the healing stage. Immunohistochemical analysis of CD4 positive cells and CD8 positive cells were performed using monoclonal antibodies to these lymph nodes. Then the number of the positive cells per square millimeters of a granuloma was estimated using a computerized analytic system for light microscopic figures. The number of CD4 positive cells per square millimeter of a granuloma was almost constant from the early stage to the mature stage, but inclined to decrease in the healing stage; on the other hand, the number of CD8-positive cells per square millimeter of granuloma decreased extremely in the mature stage, compared with the early stage and the healing stage. Moreover the CD4/CD8-positive cell ratio in granulomas, calculated from these data, was elevated in the mature stage, compared with the early and the healing stages. From the above results, the CD4/CD8-positive cell ratio in a granuloma was demonstrated to be a valuable index for evaluating the histological activity of the granuloma of sarcoid lymph nodes. Furthermore, the decrease of CD8-positive cells in mature stage granuloma was considered to be related to the maturation of the epithelioid cell granulomas in sarcoidosis. PMID- 2214414 TI - [Lung injuries and serial bronchoalveolar lavage findings in patients with summer type hypersensitivity pneumonitis]. AB - To evaluate acute lung injuries and their persistence in patients with summer type hypersensitivity pneumonitis, repeated bronchoalveolar lavage (BAL) and pulmonary function tests were performed. BAL was performed on 36 occasions in 17 patients with hypersensitivity pneumonitis. Nineteen BAL procedures in 16 cases were done during the active phase within the three hospital day and BAL was repeated in 8 cases during inactive phase. Anti-Trichosporon cutaneum antibodies were detected in all of 15 cases examined using the Ouchterlony method and indirect immunofluorescent methods. The number of total BAL cells, lymphocyte and neutrophils were increased in the active phase, and OKT4/OKT8 was quite low (0.39). As the disease became inactive, the number of total BAL cells, lymphocytes and neutrophils decreased. On the other hand OKT4/OKT8 increased quickly. Significantly negative correlations were recognized between the number of BAL lymphocytes and %VC, and lymphocytes and %DLCO4. More improvements in BAL findings, %VC and %DLCO one year after acute episodes were seen in cases that moved house than cases that did not move, and these often relapsed. We concluded that complete clearing of the patient's house or moving out, if necessary, were needed to avoid relapse and persistent lung injuries. PMID- 2214415 TI - [Improvement in alveolar macrophage function after therapeutic lung lavage in pulmonary alveolar proteinosis]. AB - Alveolar macrophage (AM) function was investigated in 4 cases of pulmonary alveolar proteinosis (PAP). Therapeutic bronchoalveolar lavage (BAL) with a flexible bronchofiberscope was done 7-13 times during periods of 4-24 weeks. In the initial BAL, the total cell count was only 0.18-0.92 x 10(5)/ml. Also low AM, lymphocytosis and eosinophilia values were noted. The phagocytic activity of AM was only 3-14% and nitroblue tetrazonium (NBT) reduction of AM was under 5% before therapeutic BAL. However, the phagocytic activity was from 25-63% and NBT reduction from 15-35% after therapeutic BAL, AM function with periods of remission of PAP was normal but AM function decreased during relapse and exacerbation of PAP. After therapeutic BAL, two patients have been in remission for three years, one patient with incomplete restoration of AM function relapsed after one year, and one patient without restoration of AM function showed further deterioration after developing pulmonary tuberculosis. These findings indicate that the defect in AM function found in PAP is reversible with therapeutic BAL, and that the severity of PAP is closely associated with AM function. PMID- 2214416 TI - [Their titers and recognized molecules of IgG class anti-BCG antibody in sera from patients with tuberculosis]. AB - Hypergammaglobulinemia is a frequent complication of tuberculosis. Serum levels of each class of immunoglobulin were analyzed among tuberculosis patients. Adult patients had high levels of IgG and IgA, but IgM levels were not elevated. These data suggested that antibody responses to mycobacterial antigens might be influenced by individual immune responses. In order to analyze the specific antibody responses to mycobacterial antigens, IgG class antibodies reactive with BCG proteins were enumerated by an enzyme-linked immunosorbent assay (ELISA). Patients were shown to have significantly higher a mount of IgG antibodies than healthy controls. Sera from patients with active tuberculosis had high consistently titers of antibodies. Antibody titers returned to a normal range after effective treatment, suggesting that the measurement of IgG anti-BCG antibodies would be useful for the diagnosis and follow-up of tuberculosis. In addition, serum antibody profiles were analyzed by immunoblotting. Sonicated whole BCG proteins were electrophorased and transferred to nylon sheets by Western blotting. Then the sheets were developed with sera from patients or controls. Mycobacterial cell wall contains a vast array of proteins so that comparison of the antibody profiles from different sera revealed striking individual variations. However two kinds of proteins, whose molecular sizes were 65KDa and 16KDa, were considered to be significant. The 65 KDa protein was recognized in most sera from both patients and controls. The protein may be related to a "common antigen" present in a wide variety of bacteria. These observations may shed a new light on the role of 65KDa protein in the regulation of the immune systems, for example a individual highly primed to 65KDa protein may amount an exaggerated and potentially harmful response to cross-reactive antigens from other essentially non-pathogenic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214417 TI - [Ultrasonographic analysis of splenomegaly in patients with sarcoidosis]. AB - Thirty seven patients with sarcoidosis were examined using ultrasound (US) to determine the size of the spleen. A Spleen Index (SI) was employed to evaluate splenomegaly and the SI was calculated using long (a) and short (b) dimensions on the sectional splenotomogram (SI = a x b). In 21 (57%) of these patients the spleen was judged ultrasonographically to be enlarged (SI 30), but in only 3 was it palpable. The clinical records of patients with and without splenomegaly detected by US were compared. There were no differences between patients with or without splenomegaly in hematologic findings (peripheral blood and bone marrow) or blood chemistry; furthermore no patients with hypersplenism were seen. In immunological parameters, the serum immunosuppressive acid protein level was significantly (p less than 0.05) higher in patients with splenomegaly than in those without splenomegaly; however, there were no differences in serum angiotenins converting enzyme activity, serum lysozyme level, PPD skin test or bronchoalveolar lavage fluid analysis. The patients with splenomegaly had significantly higher evidence of increased uptake of 67-Gallium in lung fields and positive lung infiltrates in chest X-ray than those without splenomegaly (p less than 0.01, p less than 0.05). These data suggest that ultrasound is a promising diagnostic tool for the assessment of the size of the spleen and is useful to detect disease activity and extent of disease in sarcoidosis. Patients with sarcoidosis who had splenomegaly had more disseminated disease, especially pulmonary parenchymal disease, than did those without splenomegaly. PMID- 2214419 TI - [A resected case of endobronchial metastasis from breast carcinoma]. AB - A 54-year-old woman, who had received left radical mastectomy 12 years previously, was admitted with persistent cough and hemoptysis. Plain chest X-ray film showed no abnormality but fiberoptic bronchoscopy revealed that a polypoid lesion occluded the right truncus and the surrounding bronchial mucosa was firm and edematous. Biopsy specimen demonstrated adenocarcinoma. Right middle and lower sleeve bilobectomy was performed. The tumor occupied mainly the outer and submucosal layer of the bronchial wall. Histologically, this tumor showed scirrhous adenocarcinoma with the same pathologic appearance as the primary breast lesion. It is considered that endobronchial metastasis from breast carcinoma is not particularly uncommon, therefore any patient with a past history of breast cancer and respiratory symptoms should undergo fiberoptic bronchoscopy, particularly when the chest X-ray is normal or shows non-specific changes. PMID- 2214418 TI - [Two cases of budgerigar breeder's lung]. AB - We report 2 patients with Bird breeder's lung associated with keeping budgerigars. Patient 1 kept a budgerigar indoors for 13 years. Histological examination revealed fibrosis and granulomatous changes in the alveolar septa. Among T lymphocyte subsets in BALF, helper T cell were increased. In the serum, precipitating antibodies to budgerigar dropping extract were observed. Patient 2 had kept Budgerigar for 7 months. Histologically, alveolitis was the primary finding, and suppressor T cell in the BALF were increased. Precipitating antibodies to budgerigar dropping extract was observed only in the BALF but not in serum. In patient 1 who showed a chronic course and granuloma formation, helper T cell in the BALF were increased while in patient 2 who showed an acute course and alveolitis, suppressor T cell in the BALF were increased, and precipitating antibody was observed only in the BALF. These findings suggest that T lymphocyte subsets in the BALF differ depending on the stage of hypersensitivity pneumonitis, and specific local antibody production precedes systemic antibody production. PMID- 2214420 TI - [A case of obstructive sleep apnea syndrome remarkably improved by gastric restriction surgery]. AB - A 23-year-man with morbid obesity and obstructive sleep apnea syndrome (OSAS) was admitted. He was 170 cm in height and 170 kg in weight. He underwent dietary treatment several times, but his weight returned to its original level, or even higher, within a short period. A diagnosis of OSAS was made by nocturnal polysomnography. In this morbidly obese patient with OSAS a nocturnal sleep apnea study was performed before and after weight reduction surgery (gastric restriction). The postoperative findings revealed a dramatic body weight reduction. At the same time, the results of apnea and oxygen desaturation were remarkably improved too. These results indicate that weight reduction surgery is a definitely effective treatment for morbid obesity associated with OSAS. PMID- 2214421 TI - [A case report of diaphragmatic flutter]. AB - A 18-year-old female complained of a dyspneic sensation and involuntary movements in the epigastrium. On physical examination, fine rhythmic movements in the epigastrium were observed on each inspiration with a rate of 5-10 per breath. Arterial blood gas analysis was normal. Recording of the respiratory parameters and the EMG of respiratory muscles were performed. Analysis of the respiratory flow revealed that her spontaneous inspirations consisted of short inspirations (i.e., flutter wave) (150-170 beats per minute). EMG of respiratory muscles demonstrated that these flutter waves were driven by intercostal muscles and diaphragm. The flutter waves were not suppressed by breath holding at the maximal inspiration. With intravenous injection of 200 mg of diphenylhydantoin, flutter waves disappeared within 10 minutes. There were no abnormal findings on chest roentgenogram, electrocardiogram, head CT scan and MRI of the cervical spine. During one year's follow up no attack developed again. We have encountered 3 cases of the syndrome since 1981. In two of them, the spontaneous respiration was superimposed on a high-frequency wave throughout the whole respiratory cycle while in one case the high-frequency wave developed only in the inspiratory phase of spontaneous respiration. In the present case the respiratory flow pattern was similar to the last mentioned and the EMG-analysis of respiratory muscles confirmed that the flutter waves were driven by intercostal muscles and diaphragm. Furthermore, synchronization of activities of the two respiratory muscles suggests that the syndrome is of central origin. PMID- 2214423 TI - [A morphometric study in ordinary lungs of bronchial dimensions throughout the airway tree as a basis for the analysis of COPD]. AB - A morphometrical method was established to estimate the initial dimensions of bronchi in the state in which they are strongly deformed due to narrowing or ectasis, and to enable the determination of the grade of deformity. In ordinary lungs from 16 autopsy cases, the dimension of airways were correlated with that of the accompanying pulmonary arteries to establish a standard for the estimation of the former from the latter. In each case, cross-sectioned pairs of an airway and an artery were sampled so as to cover the entire range from segmental bronchi to respiratory bronchioles. The varyingly constricted state of airways and arteries was standardized by measuring the perimeter length L of the epithelial basement membrane (BM) for airways and the internal elastic membrane (IEM) for arteries with a digital image analyzer, and reducing these into a circular state with completely stretched BM and IEM, where D(br), the anatomical diameter of airway, and D(pa), that of artery, were calculated from L. In addition, the sectional area of the epithelium was measured to calculate Rs, the ratio of luminal stenosis by epithelial thickening. In every case, a close correlation was shown to exist between D(br) and D(pa) on bilogarithmic coordinates: When all the measurements from 671 pairs of D(br) and D(pa) were pooled, the correlation coefficient proved to be as high as 0.91 (p less than 0.001). This allows estimation of the dimension of an airway from that of the accompanying artery, even when the airway is severely deformed like in COPD. The range of D(br) for the bronchi (B), that for the membranous bronchioles (MB) and the respiratory bronchioles (RB), were shown to overlap between the neighboring ranges.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214422 TI - [A case of acute lupus pneumonitis followed by high-resolution CT]. AB - A 43-year-old woman was admitted to our hospital because of fever and dyspnea. She had facial rash, hair-loss, arthralgia, urinary casts, thrombocytopenia, lymphocytopenia, and deposits of IgG, IgM, C3 in the epidermis. SLE was diagnosed. She also had severe dyspnea, which gradually progressed. In spite of steroid pulse therapy and cyclophosphamide, she eventually died about two months after admission. Chest X-ray film showed bilateral ground-glass shadow and volume loss. High-resolution CT of the lung showed marked high density area with airbronchogram in the posterior part and a gradually enlarging slight high density area in the anterior area. Pathological findings of the posterior area were atelectasis and dense fibrosis. The findings of the anterior area were collapsed alveoli and dilated alveolar ducts. These findings might suggest that alveolar collapse play a major role in the course of pulmonary fibrosis of this patient. PMID- 2214424 TI - [The nature, severity and distribution of obstructive airway lesions in COPD studied by morphometry and computer-assisted 3-D reconstruction]. AB - The severity of obstructive bronchial lesions and their distribution in the airway tree were studied in autopsy lungs from ten patients with various types of chronic obstructive pulmonary disease (COPD), where the changes of bronchial dimension were studied by morphometry and the 3-D distribution of obstructive lesions by computer-assisted 3-D reconstruction. A case of paraquat intoxication was added in order to study the airway changes in lungs with early fibrotic changes. In each case, morphometry was performed on microscopic lung sections where the initial diameter of bronchi was estimated from that of the accompanying pulmonary arteries. The varyingly constricted airways and arteries were standardized into a circular state by measuring the perimeter length L of the epithelial basement membrane (BM) and the internal elastic membrane (IEM) with a digital image analyzer; D(br), the anatomical diameter of an airway, and D(pa), that of an artery, were calculated at this state of completely stretched BM or IEM. Rs, the ratio of luminal stenosis by thickened epithelia, was also determined from the area of epithelium simultaneously measured. Three-D reconstruction of airway was performed in cases typically representing different types of obstruction; from microscopic, sometimes macroscopic serial sections, where the 2-D images were inputted into a computer which integrated in its display a 3-D picture. It was shown that in lungs with chronic bronchitis, the bronchial dimension did not significantly differ from that of ordinary lungs. Overt shrinkage of bronchial dimension was demonstrated in chronic obstructive bronchiolitis; in both diffuse panbronchiolitis (DPB) and broncho-bronchiolitis obliterans (BBO), narrowing of the peripheral airways combined with ectasis of the proximal bronchi proved to be a common feature. However, reconstruction disclosed an essential difference between these in the distribution of occlusive lesions, which mainly involved the respiratory bronchioles in DPB, while in BBO, the site of obstruction was from the terminal to slightly upper bronchioles. Also in pulmonary emphysema, the pattern of bronchial dimension was a narrowing in the periphery, both in the centrilobular and panlobular types. Especially worth of attention was that the study disclosed the presence of a type of COPD hitherto poorly defined. In a patient who had a 25-year history of COPD and died of respiratory failure, the lungs, only mildly emphysematous, were shown to have uniformly narrowed bronchioles; also mucus hypersecretion and elevated Rs appeared to have contributed to the obstruction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2214425 TI - [Usefulness of a protease inhibitor (urinastatin) in ARDS with infectious diseases]. AB - The usefulness of urinastatin (UST) for adult respiratory distress syndrome (ARDS) induced by gram-negative sepsis was evaluated in clinical and experimental studies. Twelve cases of clinical septic ARDS were treated with combination therapy of UST and methylprednisolone (M-PSL). Ten out of 12 responded favorably. This result was considered to some extent to be better than that of our previous experience with single administration of M-PSL for patients with septic ARDS. Pathophysiologic experiments on UST in endotoxic status were then performed. Immediately after the intravenous administration of endotoxin to rats, serum levels of beta-glucuronidase and elastase released from PMNs were increased and pulmonary edema was observed at 48-hours after the endotoxin injection. Various degrees of pulmonary edema were also observed by the intravenous administration of beta-glucuronidase and PMNs-elastase. These changes induced by the endotoxin were significantly inhibited by the intraperitoneal administration of UST, and they were inhibited more by the combination therapy of UST and M-PSL. In an in vitro study, significantly large amounts of beta-glucuronidase and elastase were released from PMNs by incubating human PMNs with endotoxin. By adding UST to this system, the release of these PMNs proteases was inhibited. These results suggested that UST neutralizes the PMNs-elastase release in the status endotoxemics, and consequently resulted in a better prognosis in cases of septic ARDS. PMID- 2214426 TI - [Lung cancer associated with idiopathic interstitial pneumonia]. AB - Idiopathic interstitial pneumonia (IIP) is known to have a tendency to be associated with lung cancer. Clinical characteristics of lung cancer associated with IIP are discussed in this article. Thirteen cases of lung cancer associated with IIP were examined from 1975 to 1988. A total of 590 cases of lung cancer and 38 cases of IIP were observed during that period. The 13 cases of lung cancer were found to be associated with IIP during the follow-up observation of our patients. Of these 13 patients, 12 men and a woman, the average age was 68.0 years old. All these 13 cases were ex- or present smokers. Five cases of lung cancer had no symptoms, but were detected by abnormal shadows on chest X-ray. Eight cases were detected symptoms. The duration from the onset of IIP to the onset of lung cancer was 36.5 +/- 23.5 months. Primary sites of lung cancer were distributed as follows. Nine cancers were in the left lung (64%) and five cancers were in the right lung (36%). Three cancers were in the hilar region (21%) and 11 cancers were in the peripheral lung field (79%). The numbers of lung cancers were equal in upper and lower lobe. The most common histological type was squamous cell carcinoma, followed by adenocarcinoma. Most cases were in stage III or IV. Three cases were operated, 4 were treated with chemotherapy, 4 were treated with chemotherapy plus irradiation, and 2 cases were treated by BRMs. The frequency of weight loss or finger clubbing in these patients was higher than in IIP patients without lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214427 TI - [The role of thoracoscopy in pleural biopsy in cases with pleural effusion]. AB - Between April 1985 and July 1989, 125 cases with pleural effusion were admitted to our department. The causes of pleural effusion were carcinomatous pleurisy in 47 cases, infection without tuberculosis in 34 cases, tuberculous pleurisy in 17 cases, cardiac insufficiency and hypoproteinemia in 11 cases, trauma and pneumothorax in nine cases, collagen disease in two cases and unknown origin in five cases. Carcinomatous pleurisy and tuberculous pleurisy, the differential diagnosis of which is very important, comprised 37% and 14% of all cases, respectively. These diseases can be definitively diagnosed by pleural biopsy, effusion cytology and/or effusion culture. In July 1987, we introduced thoracoscopy to improve the ratio of definitive diagnoses. The ratio for carcinomatous pleurisy in the previous term, when thoracoscopy was not being used, was 59%, while that in the latter term, when it was used, was 73%. The ratio for all cases with tuberculous pleurisy was 47%. Prior to June 1987, pleural biopsies in our department were performed with a Cope needle. Using that procedure, a low positive ratio of 50% was obtained. For thoracoscopic pleural biopsies, a high positive ratio of 84% was achieved (in carcinomatous pleurisy, 13 out of 15 cases; in tuberculous pleurisy, three out of four cases). This procedure was performed with minimal patient discomfort and no serious complications. Therefore, thoracoscopic pleural biopsy is recommended as a diagnostic procedure for cases with pleural effusion. PMID- 2214428 TI - [Activated pulmonary intravascular macrophages increase pulmonary microvascular permeability in sheep]. AB - Pulmonary intravascular macrophages (PIMs) reside in the alveolar capillaries of sheep lung. However, the role of PIMs activation in the mechanism of increasing pulmonary microvascular permeability is not clear. We determined, using awake sheep with chronic lung lymph fistulas, the effects of intraarterial infusion of latex beads emulsion (1 microns in diameter) on lung lymph-dynamics. Sheep were divided into 3 groups; control, low dose latex and high dose latex groups. In control group, their lymph-dynamics were stable during the experimental period. In low dose latex group (5.46 x 10(9) beads/kg), lung lymph flow increased during the infusion period, but lung lymph protein clearance did not change. In high dose latex group (5.46 x 10(10) beads/kg), lung lymph flow began to increase during the infusion period and remained high, and lung lymph protein clearance increased significantly during and after the infusion of latex beads emulsion. The latex beads mainly distributed to lungs, and 70% of the beads were caught by PIMs in their phagosomes. These findings suggest that the activation of PIMs through their phagocytic uptake of circulating microparticles increases pulmonary microvascular permeability. PMID- 2214429 TI - [A case of asthma exacerbated by sulfite contained in betamethasone]. AB - Adverse reactions to preservatives contained in food and medications have been recognized with increasing frequency. We have recently seen an asthmatic patient in whom wheezing and dyspnea increased after injection of betamethasone. The patient was a 26-year-old woman who had had bronchial asthma since 1980. She was treated at another hospital for moderate wheezing and betamethasone injections were given in May 1988. After this treatment her condition deteriorated acutely and she was transferred to our hospital. To confirm the possible relationship between betamethasone (sulfite) and asthmatic attack, provocation challenge tests were conducted. Intradermal skin test revealed an immediate positive reaction to sodium bisulfite at a concentration of 100 mg/L. Challenge test with increasing amounts of sodium bisulfite showed a 52% decrease in FEV1, 50 min after inhalation of 5 mg/ml solution. In addition, another inhalation challenge was conducted by use of an Astograph. Rrs immediately increased during inhalation of 10 mg/ml solution. These results suggested that sulfite contained in betamethasone preparation provoked exaggerated bronchospasm in this patient. PMID- 2214430 TI - [Severe bronchial reaction induced by hydrocortisone sodium succinate in an aspirin-sensitive asthmatic patient]. AB - This is a report of a female patient who had an anaphylaxis-like reactions to hydrocortisone sodium succinate (Saxizon). A 31-year-old female with intrinsic bronchial asthma and aspirin sensitivity was admitted to our hospital because of an episode of asthmatic attack. The patient had had episodes of dyspnea since 1976, and had been treated with oral bronchodilators and intermittent corticosteroids. After admission, she was given 100 mg of hydrocortisone sodium succinate intravenously. A few minutes later she developed severe bronchospasm and lost consciousness. An endotracheal tube was inserted and she was mechanically ventilated for 2 hours. The patient recovered after 1 hour. An inhalation challenge test with Sulpyrin was positive. When the provocation challenge test with 100 mg of hydrocortisone sodium succinate (Saxizon) injection was performed, she developed subjective and objective evidence of bronchospasm. Intradermal skin test revealed positive immediate reactions to Saxizon, Solu cortef, Predonine. It is suggested that she had immediate hypersensitivity to hydrocortisone sodium succinate, but the mechanism of this anaphylaxis-like reaction to steroids is not certain. PMID- 2214431 TI - [An open lung biopsy case of follicular bronchiolitis in rheumatoid arthritis]. AB - A 49 year-old Japanese female with a clinical history of rheumatoid arthritis for 15 years developed fever, cough, sputa and exertional dyspnea. A chest x-ray showed right-sided pleural lesions in addition to persistent hyperinflation of the lungs for about four years. Pulmonary function tests showed combined obstructive and restrictive dysfunction, increased residual volume and reduced diffusing capacity. After an improvement of the pleural lesions, she underwent a right open lung biopsy in December 1988 which revealed follicular bronchiolitis and fibrino-fibrous pleural thickening. The pulmonary lesion of follicular bronchitis/bronchiolitis was reported in 1985 as a newly recognized pulmonary disorder among open lung biopsy cases. The present case was the second biopsy proven case of follicular bronchiolitis among the Japanese. PMID- 2214432 TI - [A case of bronchial asthma complicated with mediastinal, subcutaneous, peritoneal and epidural emphysema]. AB - A case of a 16-year-old female with bronchial asthma complicated with mediastinal, subcutaneous, peritoneal and epidural emphysema was reported. The patient was admitted to our hospital because of dyspnea. Chest and abdominal X ray films revealed mediastinal emphysema with peribronchial air sheath, subcutaneous emphysema in the neck and chest, and peritoneal emphysema. CT-scan revealed severe mediastinal, subcutaneous and epidural emphysema. These findings disappeared about 10 days after recovery from the attack. Diagnostic methods and the pathogenesis of air leak were also discussed. PMID- 2214433 TI - [Study on local recurrence of squamous cell carcinoma of the lung on hilar lesion]. AB - The study population consisted of 62 patients with squamous cell carcinoma of the lung on hilar lesion who underwent curative or relative curative resection during the seven year period between January, 1980 and December, 1986. We studied the correlation between local recurrence and the distance from the surgical margin of the trachea or bronchus to the tumor. 1) As the classification of the T and N factors increased, the incidence of local recurrence became higher. 2) In order to prevent local relapse, we need to completely resect the hilar and mediastinal lymph nodes, and we must maintain a distance of 16 mm or more between the surgical margin of the trachea or bronchus and the tumor. PMID- 2214434 TI - [Respiratory function on exercise as a predictor of complications after lung resection]. AB - We studied the correlation between the complications after pulmonary resection and the results of exercise testing and others. The exercise testing was performed preoperatively on 64 patients; 44 lobectomies, 6 bilobectomies and 14 pneumonectomies. The results which had the correlation with postoperative complications were RV/BSA (p less than 0.001), RV/TLC (p less than 0.005), VE/VCO2 (p less than 0.001) and VO2/VE (p less than 0.001). Men had more complications than women (p less than 0.001). And the patients with the past histories concerning cardiovascular disease, pulmonary disease and/or diabetes had more chances of complications than the patients without those histories (p less than 0.05). Judging from these results we concluded that the patients with one or more of the following results had more chances of postoperative complications. 1. maximum VO2/VE was less than 40 ml/l. 2. VE/VCO2 was more than 4.0 l/ml. 3. RV/BSA was more than 1.5 l/m2. 4. RV/TLC was more than 45%. PMID- 2214435 TI - [A case report of the reinforcing technique with collared prosthesis for the prosthetic valve endocarditis in mitral position]. AB - A 58-year-old female was admitted to our hospital because of the prosthetic valve endocarditis in mitral position. In the past, this patient was undertaken double valve replacement in mitral and aortic position. Nevertheless, postoperative course was not in stable condition, showing persistent sign of the infection. The appearance of mitral regurgitant murmur and regurgitant signal by colour Doppler cardiography could make sure of the diagnosis for prosthetic valve endocarditis (PVE) in mitral position. The operation for PVE in mitral prosthesis was undertaken as follows. As there was extensive annular infection around the mitral valve, the new mitral prosthesis (Duromedics valve) with the Gore-tex flange, so called collared prosthesis, was revised. The collared prosthesis was implanted in the mitral annulus by using the suture ring of the Duromedics valve as well as possible, furthermore, the Gore-tex flange were sutured in the left atrial wall 2 cm above the mitral ring. Postoperatively, the infection sign and congestive heart failure were completely subsided. This patient has been in very healthy condition these days and restored to the daily life. PMID- 2214436 TI - [Surgical treatment of cor triatriatum: report of four cases]. AB - Four cases of cor triatriatum are reported. Cases 1 and 2 had IIA, case 3 had IA, and case 4 had IIIB 1 type of cor triatriatum according to Lucas-Schmidt classification. Cases 1 and 2 were diagnosed by echocardiography preoperatively. They were not performed cineangiocardiography because of pulmonary congestion. Case 3 had type IA so called classical type, which is hemodynamically identical to mitral stenosis and supravalvular stenosing ring. The clinical features are depend on the size of the communication between accessory chamber and true left atrium. As case 4, he had been diagnosed of simple atrial septal defect preoperatively, careful echocardiographic examination was essential for accurate diagnosis. In case 2 with hypoplastic left heart, secondary surgical repair is considered to be desirable followed by balloon dilatation of two atrial septal defects communicated to accessory chamber and to true left atrium. Thus, we expect development of hypoplastic left ventricle. PMID- 2214437 TI - [Giant cell tumor of the bony thorax]. AB - Two cases of giant cell tumor of the bony thorax are described. Case 1 presents a 21-year-old female with a recurrent giant cell tumor of the third and the fourth thoracic vertebrae that directly compressed the membranous portion of the trachea and brought about severe air way obstruction. The tumor was completely resected and the patient remains healthy without recurrence 30 months after surgery. Case 2 presents a 18-year-old female with a giant cell tumor invading transverse process of the seventh thoracic vertebra and the seventh rib and making a big mass in the thoracic cavity on the right side. This patient was first seen with hemothorax and treated just by tube drainage three months before undergoing total resection of the tumor. She remains well nine months after surgery. PMID- 2214438 TI - [Eleven cases of ASD in individuals aged over 50 years]. AB - Eleven cases of ASD were experienced in subjects aged more than 50 years. The ages ranged from 50-68 years (mean: 57.1 years), and there were 6 males and 5 females. The preoperative NYHA class was I in three cases, II in six cases, and III in two cases. The pulmonary arterial pressure ranged from 20-46 mmHg (mean: 30.9 mmHg), the PP/PS 0.19-0.42 (mean: 0.25), the QP/QS 1.4-3.5 (mean: 2.3), and the left to right short circuit rate was 38-73% (mean: 58.6). A patch closure operation was performed in all cases except two. After operation, the NYHA class improved in all cases except one. The CTR decreased from 59.3 +/- 6.05% to 54.1 +/- 5.07, and the pulmonary arterial pressure from 30.3 +/- 6.65 mmHg to 21.4 +/- 5.04 mmHg (improving in all cases). PMID- 2214439 TI - [Dissecting aortic aneurysm in siblings without Marfan's syndrome]. AB - The occurrence of dissecting aortic aneurysm in 2 or more family members is rare. We reported two cases of dissecting aortic aneurysm in one family. Case 1. Brother. A 49-year-old male, was diagnosed to have acute dissecting aortic aneurysm (DeBakey type I) with mild aortic regurgitation. He was operated on by valvuloplasty and closure of the false lumen, and is alive and well at the present time. Case 2. Sister. A 60-year-old female, was diagnosed to have chronic dissecting aortic aneurysm (DeBakey type II). She underwent replacement of the ascending aorta with a Dacron graft. She is alive and well. Neither of these 2 patients nor other family member had any features of the Marfan's syndrome. Histological examination of 2 cases showed the degeneration of smooth muscle in the media. Among their family, mother died of unidentified heart disease. PMID- 2214440 TI - [A successful surgical repair of ventricular septal perforation following acute myocardial infarction in a 83-year-old man]. AB - A 83-year-old man, who experienced a sudden severe malacia 13 days before, was admitted, complaining of dyspnea since 8 hours before. A loud systolic murmur of Levine IV/VI was audible on the left sternal border of the 4th intercostal space. The chest X-ray film demonstrated severe pulmonary congestion. The ECG showed abnormal Q waves in II, III, a VF and V1-5. The right heart catheterization revealed an intraventricular shunt from left to right and thus ventricular septal perforation (VSP) 13 days after acute anteroseptal-inferior myocardial infarction was diagnosed. Continuing an aggressive medical treatment with the intraaortic balloon pumping, an emergency operation for VSP was performed 2 days after the onset. A single Teflon patch was sutured on the left side of the septum around VSP (2.5 x 2.5 cm) and the ventricular free wall was closed including the patch with two felt strips. The patient survived through the operation and is doing well at the 11 months of follow-up. Twenty patients above 70 years old have been surgically treated with success for VSP after acute myocardial infarction in Japan. Our patient was the oldest. PMID- 2214441 TI - [Two cases of supposed metastasizing leiomyosarcoma of the uterus]. AB - Case 1. A 57-year-old female had hysterectomy 10 years ago because of leiomyoma uteri. She was recently found to have a clear-cut round mass shadow in the right middle lung field on her chest X-ray film 3. The mass was resected and microscopically diagnosed as metastatic leiomyosarcoma. Re-examination of the pathological specimen of the uterine tumor resected 10 years ago revealed 5-9 mitosis per 10 high-powered fields (/10 HPF). Case 2. A 54-year-old female who had undergone hysterectomy for myoma uteri 9 years previously was found to have a well-defined oval shadow in the left lower lung field which was resected and pathologically diagnosed as metastatic leiomyosarcoma. Her uterus lesion microscopically revealed 1-2 mitosis/10 HPF. The relationship between metastatic leiomyosarcoma of the lung and mitotic activity of leiomyoma uteri was discussed. PMID- 2214442 TI - [A malignant thymoma combined with sarcoidosis]. AB - A case of 69-year-old female of malignant thymoma with sarcoidosis was experienced. Although many diseases such as myasthenia gravis are associated with thymoma, sarcoidosis is a rare thymoma-associated disease. Only one case of thymoma with sarcoidosis was reported all over the world, and our case is the first case in Japan. As thymus is essential for the development of T lymphocytes, thymoma may cause T lymphocytes disorder and sarcoidosis. So, we consider thymoma with sarcoidosis as a syndrome rather than as a spectrum of coincidental disease. PMID- 2214443 TI - [A case report of coronary artery fistula into the left ventricle]. AB - Communication of the right coronary artery with the left ventricle is considerably rare. We report a case of congenital fistula of the left ventricle. Closure of the fistula was successfully done by Symbas' modification. Thirty cases with coronary artery fistula to the left ventricle reported in Japanese literatures, including our case were reviewed in regard to its surgical treatment. PMID- 2214444 TI - [Right ventricular thrombosis due to familial heparin cofactor II deficiency]. AB - This case report was with regard to familial heparin cofactor II (HC II) deficiency. The patient was a 14-years-old female, having complaints of chest pain, fever and swelling of right lower extremity. Echocardiography and DSA showed a pediculated mass at the right ventricular outflow tract which highly suggested a ventricular myxoma. At surgery, a large pediculated thrombus was removed from the RV conus septum aun pulmonary valve. The mass was identified as thrombus by histological examination. Two months later, the RV thrombi recurred with additional pulmonary embolus to the left lung. HC II was discovered by hemo coagulation tests. Her HC II antigen value was 48%, and 32% on repeat study. Her brother's HC II antigen value was 53%. At reoperation, small thrombi less than phi 10 mm, were removed from the RV outflow tract and pulmonary valve. Fresh frozen plasma was given and intravenous urokinase therapy was taken. She is doing well with therapy of oral warfarin, aspirin and ticlopidine for anticoagulation. PMID- 2214445 TI - [A case of chondrosarcoma arising from the left first rib]. AB - A 46-year-old female was admitted to our hospital because of a left supraclavicular tumor. The chest CT scan and MR imaging revealed that the tumor arose from the left first rib and developed into the supraclavicular region. In this case, we tried to resect the tumor using the so-called "trap-door" thoracotomy. Although removal of subclavian vessels and brachial plexus from the tumor was easily performed, we could not enough treat the vertebral side of the first rib through this thoracotomy without the T1 nerves injury. In cases of superior sulcus tumors developing into the posterior chest wall, a posterior incision combined with an anterior one will be useful to remove these tumors safely. PMID- 2214446 TI - [A successful surgical case of ruptured thoracoabdominal aneurysm]. AB - A successful surgical case of ruptured thoracoabdominal aortic aneurysm was reported. The patient was a 77-year-old male. He entered our hospital and was diagnosed ruptured Crawford type 3 thoracoabdominal aortic aneurysm by chest X ray, CT scan and aortography. Operative procedure was tube graft insertion into thoracoabdominal aorta with celiac artery reconstruction. Postoperative course was excellent and discharged on 55th postoperative day. PMID- 2214447 TI - [A case report of descending thoracic aortic aneurysm associated with anterior spinal artery syndrome despite no marked ESP changes]. AB - A 67-year-old man underwent graft replacement for the descending thoracic aortic aneurysm with the aid of temporary external bypass. Intraoperative evoked spinal potentials (ESPs) were monitored to detect the spinal cord ischemia. Incomplete paraplegia with sensory dissociation was developed in this patient after surgery, despite well maintained ESPs throughout the aortic cross-clamping. ESPs have been widely used as a mean of detecting early impairment of spinal neural conduction during aortic surgery. However, ESPs are principally mediated through posterior and lateral column pathways and they are not always a reliable monitor to predict paraplegia in aortic surgery. PMID- 2214448 TI - [Surgical salvage of cardiac rupture: a case report]. AB - A 39-year-old man suffered from acute myocardial infarction. Echo cardiography showed the presence of intra-pericardial fluid. We had emergent operation. We successfully salvaged cardiac rupture with fibrin glue and oxy-cellulose without cardiopulmonary bypass. His post-operative course was uneventful. The patient was discharged on the seventh week after the operation. The problems of acute cardiac rupture were discussed. PMID- 2214449 TI - [Long-term follow-up studies in 211 patients with tetralogy of Fallot after corrective surgery over 10 years]. AB - A total number of 427 patients with tetralogy of Fallot who underwent corrective surgery between 1960 and March 1990, in whom 211 patients who survived the surgery over 10 years were evaluated for the follow-up studies. Hemodynamic and cardiac function studies were carried out in 101 patients at the mean interval of 15.7 years (ranges 2 to 21 years). Three methods indicated that patients with muscle resection and pulmonary valvulotomy without patch enlargement (NP) had worse results than the groups with RV patch below valve (RP) and with transannular patch (TP). Also, Holter ECG revealed ventricular arrhythmias in patients with NP were more common than the groups with RP and TP. Sixteen patients (13 with NP, 2 with TP and one with RP) were required reoperation for residual ventricular shunt in 13, residual pulmonary stenosis in 11 and tricuspid regurgitation in 2. All of these 16 patients survived operation and obtained excellent clinical status. It is concluded that patients with TOF after corrective surgery should be carefully followed with short term interval to prevent sudden death and postoperative complications. PMID- 2214450 TI - [Long-term follow-up after repair of tetralogy of Fallot]. AB - One hundred sixty-six patients with tetralogy of Fallot including 15 extreme type patients repaired since 1971 were analyzed with respect to their physical activities, school or social life, hemodynamics, ECG, reoperation and late mortality. Follow-up period ranged from 1 to 19 years with an average of 9.1. There were 9 late deaths including 4 sudden deaths. Actuarial survival rates at 10 and 19 years were 95.2% and 90.5%, respectively. Eighty-five patients (72.0%) of 118 replied were in NYHA functional class I, 31 (26.3%) in class II and 2 (1.7%) in class III. Thirteen patients (7.8%) demonstrated right ventricular/left ventricular systolic pressure ratio over 0.80 because of inadequate relief of the pulmonary stenosis or obstruction, hypoplasia of the pulmonary artery or external conduit stenosis. Although the left ventricular ejection fraction was maintained at normal range (0.65 +/- 0.09), that of the right ventricule was below normal level (0.52 +/- 0.09). Two patients developed complete heart block postoperatively and underwent pacemaker implantations. Complete right bundle branch block was observed in 85 patients including 6 with left axis deviation. It is concluded that early correction even in the early infancy, adequate enlargement of the right ventricular outflow tract and minimal right ventriculotomy should be applied for correction of tetralogy of Fallot. PMID- 2214451 TI - [Exercise tolerance after correction of tetralogy of Fallot]. AB - Twenty-six postoperative patients with tetralogy of Fallot (TF) were evaluated by exercise stress test with an upright cycle ergometer. Oxygen uptake was assessed at the anaerobic threshold and the peak achieved work load. Oxygen uptake at the anaerobic threshold (VO2AT) was in the normal range regardless of the existence of residual stenosis (PS) or pulmonary regurgitation (PR). However, oxygen uptake at the peak achieved workload (VO2max) was subnormal in patients with PS or PR. Maximal heart rate in TF patients was lower than normal. Patients with PR showed significantly reduced VO2max as compared with those without PR (p less than 0.05). This is found to be resulted from limitation of the oxygen pulses increase. PMID- 2214452 TI - [Postoperative long-term quality of life at present after total correction of tetralogy of Fallot]. AB - We performed a questionnaire study in 47 patients who underwent corrective surgery for tetralogy of Fallot (TF) more than 10 years previously. To evaluate quality of life, we used well-being score advocated by Kaplan. 12 patients whose well-being score was 1.0 were in entirely good health without any complaints. Well-being score of patients averaged 0.773 with the range from 0.58 to 1.0. The patient with high RV/LV pressure ratio or large CTR tended to have a low well being score. Grade of Lown classification did not correlate to well-being score. PMID- 2214453 TI - [Longterm result of standardized patch infundibuloplasty and its application to conotruncal repair in tetralogy of Fallot]. AB - Longterm result more than 10 years of standardized patch infundibuloplasty which had started in 1974 was reviewed. Thirty four cases were categorized into three groups. Group A: patch infundibuloplasty less than 45% of RV length. Group B: patch infundibuloplasty more than 45%, Group C: non-cusped transannular patch. Group B had longer patch infundibulolasty than group A and C. RV/LV pressure ratio of group C was higher than that of group A and B. There was no significant difference in CTR. However, when the cases with CTR more than 55% were precisely compared, enlarged CTR was related to high RV pressure and pulmonary regurgitation in group C while it might result from residual shunt in group A and B. Although longterm result of standardized patch infundibuloplasty was good, even small pressure and volume load in RV should be avoided as much as possible. Based on this longterm result, the conotruncal repair has been introduced and its better longterm result would be expected. PMID- 2214454 TI - [Late results after open repair of tetralogy of Fallot: a 13-24 year follow-up]. AB - Late results in 139 patients undergoing open repair of tetralogy of Fallot from 1965 to December 1975 were analyzed. Their ages ranged from 1 year to 35 years. All patients were repaired through a right ventricular approach. One hundred two patients had infundibulectomy alone (non-patch group) and 14 required right ventricular outflow patch (RV-patch group) and 23 trans-annular patch. The hospital mortality rate was 18.7% (26 cases) and 103 patients were discharged and have been followed until death or for 13-24 years. Cardiac catheterizations were performed in 80 patients an average of 1.8 years after correction. Right ventricular systolic pressure was 49.8 +/- 22.4 mmHg in non-patch group, 41 +/- 16.5 mmHg in RV-patch group and 54.5 +/- 14.2 mmHg in PA-patch group. Seven in 11 patients of PA-patch group had over an 8 mmHg of right ventricular end diastolic pressure. Six patients died during the follow up: four deaths in the first 5 years, 2 between 5 and 15 years. The causes of death were congestive heart failure (3), sudden (1), pneumonia (1) and accidental (1). Late complications were 3 arrhythmias and 2 reoperations. Event free rate at 24 years was 74.8 +/- 3.8%. PMID- 2214455 TI - [Long-term (10 to 23 years) clinical evaluation of quality of life in patients following open heart repair of tetralogy of Fallot]. AB - The quality of life of 78 patients out of 79 (99% follow-up rate) was evaluated 10 to 23 years following intracardiac repair of tetralogy of Fallot. Mean age at operation was 6 years of age. Their present ages ranged from 12 to 35, averaging 21 years old. Eighty three percent of patients are assessed to be in good quality of life so far in terms of physical development, life style, CTR values, Ekg findings and so on. Pregnancy and delivery in 5 patients were uneventful. On the other hand, 17% showed various degree of morbidity including significant residua necessitating reoperation in 3 patients, complications such as complete A-V Block requiring pacemaker implantation in 7 and sequela like postoperative life threatening cardiomyopathy in 3. There were 2 deaths due to this sequela comprising 2.6% of mortality rate. Although excellent results are reported in recent years, further efforts will be necessary to minimize residuum, complication and sequela after surgery especially for this particular disease with broad morphological spectrum. PMID- 2214456 TI - [Long-term follow-up (20 to 25 years) of tetralogy of Fallot after correction]. AB - Eighty patients with tetralogy of Fallot who underwent corrective surgery between 1965 and 1970 were followed and evaluated. Late death was observed in 8 patients, and 3 of them were cardiac deaths. The survival rate at 10-year was 96.2%, at 20 year was 91.7%, and at 24-year was 89.0%. Of the surviving patients, 78% to 85% are spending normal social life. Twenty female patients experienced 31 deliveries, and no babies with cardiac anomaly were born. Most of the complaints come from late arrhythmias, and this is the main problem in the long-term period. Right ventricular function is considered to be moderately reduced by catheter analysis. The importance of preservation of right ventricular function during the surgery should be stressed. PMID- 2214457 TI - [Late results after total correction of tetralogy of Fallot: over 10 year follow up]. AB - Late results after total correction of tetralogy of Fallot over ten year follow up of 84 patients were discussed. No late death was experienced and 95.1% of these patients are now in NYHA class I. Reoperations were performed in 7 cases (8.3%) in which six had had residual shunt and one had had sick sinus syndrome and had VVI pacemaker implantation. Ten cases had over 90% of ratio of right ventricular pressure to systemic pressure in systole in their cardiac catheterization about 40 days after correction. In spite of this high pressure ratio, all cases are now in NYHA class I. We conclude that there is a possibility of enabling to preserve pulmonary valve function by adopting smaller criteria than the Pacifico's criteria. PMID- 2214458 TI - [Long-term results after total correction of tetralogy of Fallot]. AB - One hundred sixty-two patients underwent total correction of tetralogy of Fallot from 1962 to 1979. 130 of these were hospital survivors. We studied the current status of the hospital survivors by questionnaires which were sent to 93 patients. An excellent long-term result was maintained by 87.3% of the 63 hospital survivors who answered to the questionnaires. Although there was a trend toward a higher incidence of symptoms in patients with a higher late postoperative RV/LV pressure ratio and in patients with older age at repair, it did not reach statistical significance. Six patients in this series have undergone reoperation. The most common cardiac problem which required reoperation was residual of the VSD. There was one late sudden death postoperatively. The RV/LV pressure ratio of the patient was 0.7 and the electrocardiogram at rest showed no abnormality except CRBBB. The ventricular dysarrhythmia was supposed as the cause of sudden death. The patients who underwent total correction of tetralogy of Fallot should be followed up by exercise ECG or 24 hours electrocardiographic monitoring. PMID- 2214459 TI - [Long-term evaluation after correction of tetralogy of Fallot]. AB - The long-term survivors of the patients who underwent corrective surgery for tetralogy of Fallot between 1956 and 1988 were analyzed with respect to symptoms, late death, reoperation, and ventricular arrhythmias. For analysis, these 380 patients were separated into three periods, April 1956-December 1968 (Period 1), January 1968-May 1978 (Period 2), and June 1978-December 1988 (Period 3). In Period 3, the intracardiac procedures were performed with or without minimal right ventriculotomy. There were 24 late deaths (6.3%), and 10 of them were sudden. Nine patients (2.4%) required reoperation. Actuarial reoperation free survival rate was 93.8% at 10 years, 90.0% at 20 years, and 85.3% at 30 years. There were no differences in the actuarial curve between 3 periods though there was no late death in Period 3. NYHA functional class was I in 229 (80%) out of all 287 patients whose symptoms were clear to follow up, II in 50 (17), and III in 8 (3%). There was no patient in NYHA class IV. The incidence of NYHA class II and III was significantly higher in Period 1 (23%) and 2 (28%) than Period 3 (7%) (p less than 0.01, p less than 0.01). Ventricular arrhythmias were evaluated in 155 patients with ambulatory electrocardiography. Significant ventricular arrhythmias of Lown's grade 2 to 4 were detected in 52 patients (34%). The incidence of significant ventricular arrhythmias of Lown's grade 2 to 4 was significantly higher in Period 1 (50%) and 2 (53%) than Period 3 (15%) (p less than 0.01, p less than 0.01). Thus symptoms and ventricular arrhythmias increased when the follow-up interval exceeded 10 years or in patients with large ventriculotomy. PMID- 2214460 TI - [Long-term result of total correction of tetralogy of Fallot]. AB - Long-term result of total correction of tetralogy of Fallot was investigated in 51 patients who underwent operation at least 10 years previously. Ninety percent of the patients who responded to the questionnaires expressed his daily life as satisfactory and 4% of the patients had no exercise limitation even in strenuous sports like swimming and running. It was disclosed that the exercise capacity in long-term period was thought to be prescribed by the developmental state of the pulmonary vascular bed at the time of operation which was expressed by the preoperative hemoglobin level and the PA/Ao diameter ratio and no correlation was found with the RV/LV pressure ratio recorded immediately after correction. Three patients died after discharge, 2 years, 2 years and 6 months and 21 years after operations respectively and the cause of death was supposed to be arrhythmia. In case of postoperative complete right bundle block associated with an extreme right axis deviation or left axis deviation, prophylactic pacemaker implantation was recommended. PMID- 2214461 TI - [Late postoperative results after repair of tetralogy of Fallot]. AB - Two hundred and eighty two survivors after complete correction of tetralogy of Fallot were analyzed in late follow up periods. The method of the reconstruction of right ventricular outflow tract was non-transannular path (NTAP) in 110 patients and transannular patch in 172. In the group of TAP, pulmonary regurgitation occurred in all and the cardio-thoracic ratio was larger than the ratio in the group of NTAP (p less than 0.05). Postoperative ECG at rest showed complete right bundle branch block (CRBBB) in 224 patients and 6 of them showed sudden death in their follow up period. However, there were no sudden deaths in 41 patients without CRBBB. The rate of reoperation after intracardiac repair was 4.25% and the causes were residual pulmonary stenosis and residual ventricular septal defect, and there were no significant differences of the reoperation rate between NTAP-group and TAP-group. PMID- 2214462 TI - [Clinical and pathological study on 47 cases of renal pelvic and ureteral tumors]. AB - 47 cases including 24 renal pelvic tumors, 20 ureteral tumors and 3 renal pelvic and ureteral tumors treated in our hospital from January, 1980 to December, 1987, were studied clinico-histopathologically. The patients ranged in age from 38 to 81 years (average 65 years) the sex ratio was 3:1 with male predominance over female. Tumor occurred on the right side in 19 cases, on the left side in 27 cases and bilaterally in 1 case. The most frequent sign was hematuria which was observed in 40 cases (85%). The interval from the onset of initial symptoms to the first visit was within one month in 9 cases (19.1%). The major findings of excretory urograms were filling defect in 21 cases (47.1%) and non-visualizing kidney in 15 cases (33.8%). Positive urinary cytology was obtained in 21 cases (44.7%). Operative therapy as performed in 45 cases, namely, nephroureterectomy and partial cystectomy in 30 cases (66.7%) and nephroureterectomy in 9 cases (20%). Histopathologically, all cases but two cases of squamous cell carcinoma and to cases of mixed type carcinoma are transitional cell carcinoma. Subsequent bladder tumors were found in 8 cases (17.7%). The overall survival rate at 1, 3 and 5 years were 80.2%, 41.1% and 41.1%, respectively by Kaplan-Meier method. In this series, the interval from the onset of initial symptoms, the grade and stage of tumor and metastasis of lymph nodes were to be considered in developing prognosis. PMID- 2214463 TI - [Therapeutic evaluation of male infertility--the increase of seminal transferrin level and the improvement in sperm concentration following administration of clomiphene citrate]. AB - This study was designed to evaluate the functional changes of Sertoli cells following the administration of clomiphene citrate for male infertility. Sperm count and seminal transferrin level were measured before and after the treatment in 22 cases of oligozoospermia (sperm count: less than 20 X 10(6)/ml) and 14 cases of subnormal sperm count group (sperm count: 20-30 X 10(6)/ml). Clomiphene citrate was administered per os for more than 3 months consecutively in a dose of 25 mg/day. Seminal transferrin concentration increased more than 1.5 times compared with pre-treatment level in 6 cases (16.7%). Among these patients, sperm count markedly increased (20 X 10(6)/ml or more than the pre-treatment level) in 3 cases (50%) and slightly increased (10 X 10(6)/ml or more than pre-treatment) in 1 case (16.7%). In 30 cases, in which seminal transferrin level did not increase, sperm count markedly increased in 6 cases (20%) and slightly increased in 6 cases (20%). Thus, sperm count was improved more frequently in the cases in which seminal transferrin level remained elevated than the cases with no elevation of serum transferrin level. Serum FSH level of patients whose seminal transferrin level remained elevated after the treatment was significantly higher than that of patients with no elevation of serum transferrin level (mean +/- SD = 32.8 +/- 18.0 mIU/ml v.s. 14.4 +/- 11.7 mIU/ml, respectively). These data suggested that the activation of Sertoli cells may contribute to the increase of sperm count following the administration of clomiphene citrate and the elevated seminal transferrin secretion may be related to the increase of serum FSH level following this treatment. PMID- 2214464 TI - [Effect of age on the amount of autonomic receptors in the rabbit prostate homogenate]. AB - The amount of autonomic receptors in the old and young rabbit prostate homogenate was measured in order to study the effect of age on the autonomic receptors of the prostate using radioligand binding techniques. For measuring the adrenergic alpha-1, alpha-2, beta-receptors and cholinergic muscarinic receptors, 3H Prazosin (3H-PZ), 3H-Yohimbine (3H-YOH), 3H-Quinuclidinylbenzilate (3H-QNB) were used, respectively. It was found that both the young and old rabbit prostate has a single class of binding sites for each ligand examined. There was an age related difference in the distribution of these autonomic receptors (young: alpha 1 = muscarinic greater than alpha 2 greater than beta, old: alpha 1 greater than muscarinic greater than alpha 2 greater than beta). There were more alpha-1 and alpha-2 receptors in the old rabbit prostate, although these differences were not statistically significant. There was no age-related differences in the amount of beta adrenergic and muscarinic receptors. These results demonstrate that the age may affect the distribution of autonomic receptors but not significantly the amount of autonomic receptors of rabbit prostate. PMID- 2214465 TI - [Treatment in 50 cases of transitional cell carcinoma in renal pelvis and ureter]. AB - A total of 50 cases of primary tumors in the renal pelvis and ureter were treated in Tokyo University Branch Hospital (20 cases in 1966-1982) and in Tranomon Hospital (30 cases in 1977-1987). They were composed of 42 men and 8 women (5.3:1) with a mean age of 61 years. 31 patients suffered from renal pelvic tumors, 15 ureteral tumors and 4 tumors in both sites. The tumors were located in the left side in 33 cases, right in 16, and both sides in 1.86% of patients showed gross hematuria. The findings on IVP were filling defect (42%) and nonvisualization (33%). Positive urine cytology was obtained in 12 of 25 cases (48%). Surgery was performed in 47 cases. The remaining 3 cases were with advanced diseases. The surgeries were total nephroureterectomy plus ipsilateral retroperitoneal lymph node dissection in 26 cases, total nephroureterectomy without node dissection in 7, total nephroureterectomy and total cystectomy in 3, nephrectomy in 9, partial nephrectomy in 1 and segmental excision of ureter with ureteroureterostomy in one. Histologically, all tumors were transitional cell carcinoma. Over-all survival rates (Kaplan-Meier's method) of the operated patients at 1, 3, 5 years were 84.2%, 73.1% and 69.4%, respectively. The stage and grade of the tumors affected the prognosis. N factor at lymph node dissection was the most determining factor of prognosis. 3 advanced cases who did not receive surgery for primary site were treated with 5FU in 2, and with CAP in 1.2 of them died of the disease within 1 year after diagnosis, one patient was lost in follow up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214466 TI - [Urinary incontinence in children with primary vesicoureteral reflux--urinary incontinence and function of refluxing kidney]. AB - The interrelation among urinary incontinence (nocturnal enuresis, urge incontinence), history of urinary tract infection and renal function was investigated in 153 children with primary vesicoureteral reflux who were more than three years old. Of them, 98 children (64%) had the chief complaint of urinary tract infection (UTI) and 43 children (28%), urinary incontinence. Of the children whose chief complaint was UTI, 44 (45%) had incontinence. Thus, 87 children (57%) with VUR had urinary incontinence. Almost all the children who had urinary incontinence and no previous UTI had good renal function. Renal dysfunction was found in children with previous UTI history. These studies on children with primary VUR more than three years old indicate that, although urinary incontinence could be a factor for recurrence of UTI and a probable cause of worsening of renal function, there is no direct correlation between urinary incontinence and renal dysfunction accompanied by VUR. PMID- 2214467 TI - [Clinical study of penile carcinoma in 38 cases]. AB - We retrospectively reviewed 38 patients with primary penile squamous cell carcinoma (stage 1 in 22, stage 2 in 7 and stage 3 in 9) who were treated in our institution from 1963 through 1987. The incidence of regional nodal metastasis was correlated with tumor category, local infiltration and tumor grade. The incidence rate of nodal metastasis of G2 and G3 tumors was statistically higher than that of G1 tumors. Of 27 patients initially treated by radiotherapy and/or chemotherapy, 11 patients achieved complete response. G1 tumors and T1 to 2 tumors had such high response rates as 58 and 50 per cent, respectively, but 5 patients (45 per cent) had local recurrence at an average of 74 months after initial treatment. The 5-year survival rates of over-all, stage 1, 2 and 3 were 73, 90, 75 and 25 per cent, respectively. Patients with stage 3 disease had a statistical lower survival rate than those with stage 1 or 2 disease. Among 13 patients with regional nodal metastasis, none with G2 tumor survived three years, although 3 patients (60 per cent) of those with G1 tumor survived five years. These results suggest that tumor grade is the most prognostic factor for the regional nodal metastasis, the response of conservative treatment and the survival of metastasized patients. PMID- 2214468 TI - [Study on adoptive immunotherapy on patients with renal cell carcinoma. I. Functional characteristics of peripheral blood mononuclear cells and serum immunosuppressive factors in patients with renal cell carcinoma]. AB - The immune responses in patients with renal cell carcinoma were evaluated from the production of interleukin-2 (IL-2), the expression of IL-2 receptors and the activity of lymphokine activated killer (LAK) cells. In addition, the effect of the patient's serum on the expression of IL-2 receptors and LAK activity were investigated. The production of IL-2 by peripheral blood mononuclear cells (PBM) from patients with renal cell carcinoma was not suppressed, when compared with that in controls. However, the expression of IL-2 receptors tended to decrease with the progression of clinical stage. The LAK cells generated by PBM of patients with renal cell carcinoma had significant cytotoxic activity against Daudi cells, ACHN cells and autologous tumor cells, while autologous serum suppressed the expression of IL-2 receptors and the induction of LAK cells in patients with renal cell carcinoma. Furthermore, serum from patients with renal cell carcinoma suppressed the cytotoxic activity of LAK cells generated by PBM from a normal volunteer. These results indicated the presence of immunosuppressive factors in the serum of patients with renal cell carcinoma which impaired the clinical effect of treatment using IL-2 or LAK cells. PMID- 2214469 TI - [Study on adoptive immunotherapy in patients with renal cell carcinoma. II. Plasmapheresis with adoptive immunotherapy using LAK cells and IL-2]. AB - The existence of immunosuppressive factors which impair the clinical effect of treatment using IL-2 or lymphokine activated killer (LAK) cells has been reported in the serum of patients with renal cell carcinoma. For the purpose of eliminating these immunosuppressive factors, plasmapheresis combined with adoptive immunotherapy using LAK cells was performed in ten patients with stage IV renal cell carcinoma. Immunological examinations revealed that the number of peripheral blood lymphocytes, NK activity and the ratio of Leu 11 positive cells were increased during the treatment. Of the 9 evaluable patients, one has a partial response, 5 showed no change and 3 had progressive disease. In addition to the one partial response, the size of some metastatic lesions in the lungs decreased in 2 patients during the treatment. As serious side effects, brain edema progressed in 2 patients with brain metastases and acute hepatitis due to plasmapheresis was noted in one patient. Moreover, transient and reversible renal dysfunction developed in most patients. These results indicated that plasmapheresis combined with adoptive immunotherapy using LAK cells is a useful therapy for patients with advanced renal cell carcinoma. PMID- 2214470 TI - [The effect of glycosaminoglycans on calcium oxalate crystal formation]. AB - The effect of glycosaminoglycans on calcium oxalate crystal formation in the supersaturated solution was studied by examining the size and shape of calcium oxalate crystals generated under an optical microscope. It was found that heparan sulfate and heparin were more effective growth inhibitors than chondroitin sulfate and hyaluronic acid at concentrations within their respective urinary range. With increasing calcium and/or glycosaminoglycans concentration in the solution, the degree of growth inhibition caused by glycosaminoglycans was enhanced. Calcium oxalate crystal shapes generated with various glycosaminoglycans varied with glycosaminoglycan species. One of the causes of those differences in the shape and degree of growth inhibition might be the structural differences between them, that is, the number of sulfate residue and O or N-form they contain. Calcium oxalate crystal shapes in the presence of heparin or heparan sulfate at higher concentrations were similar to those of calcium oxalate monohydrate crystals in the urinary sediments of hyperoxaluric patients. These facts might suggest the possibility that heparin and/or heparan sulfate were present in the crystal forming region. PMID- 2214471 TI - [Micturition and uroflowmetric analysis of adult females]. AB - Voiding parameters on the Uroflow Diagnostic Interpretation (UDI) were analysed in relation to the voided volume in 58 micturitions of 36 healthy adult females. The maximum flow rate (Qmax) and the mean flow rate during central 90% of the voided volume (QM90) increased linearly up to the voided volume of 400 ml. The voiding time (T100) took a value within a certain range independently of the voided volume from 100 to 400 ml and never exceeded 21 seconds in all micturitions. Voiding time for the central 90% of the voided volume (T90), time to Qmax (TQmax) and time from Qmax to 95% of the voided volume (Tdesc) were independent of the volume voided. The maximum rate of increase of flow rate (dQ/dT max) and the estimated bladder wall contraction velocity at 40 ml bladder contents (dL/dT 40) showed a tendency to increase depending on the volume voided. T100 showed a prolongation in 84.0% of 25 micturitions in 20 neurogenic bladder patients and in 66.7% of 27 in 21 chronic cystitis patients, always accompanied by a prolongation of T90. No other parameters were clearly different between healthy women and patients and/or between the two groups of patients. Voiding time is a useful parameter representing female micturition. PMID- 2214472 TI - [Treatment of asynchronous bilateral renal cell carcinoma. On our experience of enucleation for two cases]. AB - In patients with either bilateral renal malignancies or with carcinoma occurring in a solitary kidney, the principle of en bloc removal of the tumor-bearing kidney cannot be applied. Recently we have performed surgical enucleation in two cases of asynchronous bilateral renal cell carcinoma. Case 1. A 60-year-old woman was hospitalized with diagnosis of left renal tumor 10 years tumor 10 years after right nephrectomy for renal cell carcinoma. The tumor was enucleated while occluding the renal vessels. Pathological examination revealed that the tumor (a nodule of 35 g) was renal cell carcinoma of grade I and perfectly covered by pseudocapsule. Hemodialysis was not required. The patient has been well for more than 11 months postoperatively and Ccr is 65 ml/min. Case 2. A 62-year-old man with slight elevation of serum GOT and GPT level was examined by CT, which revealed a space occupying lesion in the left kidney. He had undergone nephrectomy for renal cell carcinoma of right kidney 11 years ago. Three nodules of 56 g, 6 g and 3 g were removed by in situ enucleation. They were renal cell carcinoma of grade II and there was no malignant penetration of the pseudocapsule pathologically. After surgery hemodialysis was required 10 times for 21 days. Renal function has been refined gradually and the patient is well with 47.3 ml/min of Ccr at 4 months postoperatively. Before this report of 2 cases there were 22 cases of asynchronous bilateral renal cell carcinoma in Japanese literature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214473 TI - [Neurogenic bladder dysfunction due to spina bifida and sacral dysgenesis manifested itself in middle age. Report of a case]. AB - Congenital neurogenic bladder dysfunction with spina bifida and sacral dysgenesis manifested itself at middle age is reported. A 48-year-old male who had urinary retention and suprapubic cystostomy one year and a half before in another hospital was seen, asking for removal of the cystostomy. He had never had any neurologic or bladder dysfunction in his childhood and adulthood. X-ray examination revealed a bifid spine and sacral dysgenesis, bilateral hydronephrosis, bilateral VUR and urethral stricture. Uroflowmetry showed a severe dysuric pattern (voided volume 5 ml, residual urine 230 ml) and the cystometrogram revealed a hyperactive bladder. Optical urethrotomy for stricture yielded some improvement i.e. recovery of voluntary voiding with large amount of residual urine. TUR of the bladder neck resulted in almost complete voiding. Cohen's antireflux operation yielded favorable improvement of hydronephrosis. The bladder and renal function remained favorable in the follow-up period of about two years. The clinical course of this patient suggested that his bladder dysfunction was due to late manifestation of congenital neurogenic bladder. PMID- 2214474 TI - [Basic and clinical research of impotence--its present situation and problems involved]. AB - From detailed investigation of the vascular structure of the penis, it has been proposed that there exists a valvular structure, consisting of smooth muscle, located at a point immediately before the helicine artery, bifurcated from the deep artery, opens to the cavernous sinuses, an area where autonomic nerves are densely distributed, participating in opening and closing the valve. On the other hand, there is said to be no valvular structure in the vein outflowing from the cavernous sinuses, and blood flows into the dorsal penile vein by penetrating the albuginea obliquely or vertically after running parallel in the region immediately below the albuginea. It is considered that, when the valve of the helicine artery opens, blood flows into the cavernous sinuses, expanding them, and as a result the outflowing vein is compressed between the sinuses and the albuginea, or the albuginea itself, acting like a valve and therefore assuming an important function in maintaining erection by disturbing the reflux of blood flow. It is also presumed that the contracting of ishiocavernous muscle plays a part in developing the rigidity of the penis. It is considered, moreover, that the trabecula of the cavernous body consisting of smooth muscle also plays a part in the promotion and disappearance of erection. It is very important to run functional tests of erection when diagnosing impotence, and today many tests are available for differential diagnosis; including papaverine test, dynamic cavernosometry and cavernosography. As for therapy, treatments involving vasoactive agent infusion, such as papaverine or prostaglandin E1 into the cavernous body, have become common. For cases with venous impotence, ligation of the penile deep vein and crus of the penile cavernous body have come to be attempted. Furthermore, revascularization of penile artery can be performed to treat arterial impotence. For cases in whom these methods are not effective, implantation of various penile prostheses into the penis has been shown to be successful. PMID- 2214475 TI - [Spontaneous resolution of reflux in children with primary VUR]. AB - Although the adverse effects of vesicoureteral reflux on the renal function and renal growth have been well documented, there is still controversy regarding the factors for spontaneous cure of reflux and the time required for the resolution. We performed a retrospective analysis of 829 ureters in 541 children who have been followed for more than 3 years since 1973. Reflux was judged as spontaneously cured only after 2 micturition cystourethrograms (MCU) had shown no reflux. In total reflux resolved in 220 ureters (26.5%) of 182 children (33.6%). Resolution rate was 39.5% in boys and 28.0% in girls, and there was statistically significant difference between both sexes. In children who had underwent urethrotomy on congenital urethral stenosis, e.g. bulbous urethral stenosis in the boy and distal urethral stenosis in the girl, resolution rate was 43% in boys and 23% in girls. Resolution rate according to VUR-grade was 85.5% in grade I and II reflux, 45.8% in grade III, and 6.7% in grade IV and V. Of 92 children who underwent urodynamic evaluations, 37% showed findings of unstable bladder. Renal scarring was observed in 7.3% of renal units which was significantly less frequent than the incidence among total renal units with reflux. Reflux was resolved in 30% of renal units without scarring and 10% of renal units with scarring. The incidence of small kidney in the spontaneously resolved group was 3.6%, which was significantly lower compared to the total renal units with reflux. The mean age at resolution of reflux was 5.7 years in boys and 7.5 years in girls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214476 TI - [A clinical evaluation of lymphography in bladder tumor]. AB - A study was conducted in a total of 51 patients with urinary bladder tumor who had received surgical operation associated with removal of regional lymph nodes after lymphography. Abnormal findings were observed in lymphogram of 22 patients. The other 29 patients showed no such abnormality. After the operation pathological metastasis was confirmed in 7 patients. Lymphograms of these patients ith positive lymphatic metastasis revealed filling defects in 85.7% and collaterals in 57.4%. There as correlation between the occurrences of these two findings based on quantification analysis III of multivariate analysis. Lymphography before operation showed 87.5% of sensitivity, 65.1% of specificity and accuracy of 68.6%, not having higher accuracy compared to other studies. These results suggest that lymphography, which may have clinical significance, is not a decisive method in exploration of bladder tumor. Comprehensive analysis of diagnostic imaging should be performed, including CT after lymphography. PMID- 2214477 TI - [The study of BBN induced bladder cancer in mice. Influence of Freund complete adjuvant and associated immunological reactions in mice]. AB - To evaluate the genetic difference in induction of bladder cancer by N-butyl-N-(4 hydroxybutyl) nitrosamine (BBN), BBN was given to two different strains of mice, i.e. A/J (BCG resistant) strains and C57BL/6 (BCG susceptible) strains. The influence of Freund complete adjuvant (FCA), which includes BCG, was similarly examined along with associated cellular immunity as evaluated by footpad reaction (FPR). The results were as follows: 1. The incidence of bladder cancer was significantly higher in C57BL/6 strains (90.0%) than A/J strains (54.5%). 2. FCA reduced the incidence of bladder cancer significantly in C57BL/6 strains. 3. FPR, which reflects the delayed type hypersensitivity, was activated significantly in FCA treated C57BL/6 strains. These data suggest that the strain differences in mice probably explains the inhibition of carcinogenesis by FCA and cellular immunity. PMID- 2214478 TI - [Intravesical bacillus Calmette-Guerin (BCG) in the treatment of superficial bladder cancer. Prospective randomized study for prophylactic effect]. AB - We report the results of prospective randomized study which was designed to evaluate prophylactic effects of intravesical bacillus Calmette-Guerin (BCG) in the treatment of superficial transitional cell carcinoma of the bladder. A total of 44 cases who had no previous treatment of bladder cancer were randomly assigned to BCG or control groups after TUR. BCG group (23 cases) received intravesical instillation of 80 mg BCG (Tokyo strain) at one week intervals for 6 weeks, at two week intervals for 12 weeks, and at one month intervals for 20 months. In BCG groups, 3 cases had recurrence at 6 months and 1 case at 9 months, while the other 19 cases had no recurrent disease for 3 to 34 months (average 20.3 months) of follow-up. Control group (21 cases) had no further treatment after TUR. In control group, recurrence was seen at 3 months in 3 cases, at 6 months in 5 cases, at 9 months in 2 cases, at 12 months in 3 cases and at 21 months in 1 case. Only 7 cases in the control group were free of recurrence for 8 to 45 months (average 32.3 months) of follow-up. One and two year-recurrence rates in BCG group (18.4%, 18.4%) was significantly (p less than 0.01) lower than those in control group (63.2%, 68.9%). Among the complications of intravesical BCG were cystitis (76.2%), low grade fever (13.0%), and several days' persistent gross hematuria (13.0%). Most of these signs were self-limited and only in 2 cases instillation of BCG was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214479 TI - Annual list of emergency nursing graduate programs. PMID- 2214480 TI - "Benign" treatments: be critical, and first, do no harm. PMID- 2214481 TI - Emergency services, emergency nursing, and the consumer. PMID- 2214482 TI - "Management of stress and prevention of burnout" conclusions questioned. PMID- 2214483 TI - Reye's syndrome reminder. PMID- 2214484 TI - More information sought on case review. PMID- 2214485 TI - Data regarding methylprednisolone therapy for acute spinal cord injuries needs to be disseminated: emergency nurses can help. PMID- 2214486 TI - Case review. A 27-year-old woman with verapamil overdose. PMID- 2214487 TI - Rural trauma: the Oregon experiment. PMID- 2214488 TI - Student internship in emergency nursing: one answer to the nursing shortage. PMID- 2214489 TI - HIV testing of sexual assault populations: ethical and legal issues. PMID- 2214490 TI - October: a harbinger of pediatric trauma. PMID- 2214491 TI - Law and the emergency nurse. Death in the ED holding area--liability? PMID- 2214492 TI - Nurse educator. "Teddy bear clinic". PMID- 2214493 TI - Triage decisions. A 59-year-old woman with acute dyspnea. PMID- 2214494 TI - Four little stitches. PMID- 2214495 TI - Emergency Nurses Association position statement. The use of nonregistered nurse (non-RN) care givers in emergency departments. PMID- 2214497 TI - Emergency Nurses Association position statement. Integration of emergency nursing concepts in nursing curricula. PMID- 2214496 TI - Emergency Nurses Association position statement. Injury prevention. PMID- 2214498 TI - Laryngostrobovideography using a flexible laryngofiberscope performed in conjunction with the phonatory examination. AB - The phonatory examination was performed while monitoring vocal fold vibration by laryngostrobovideography. Vocal fold vibration was video-taped by a laryngostroboscope and flexible laryngofiberscope inserted through the nasal cavity. Simultaneously, the phonatory examination was conducted with a phonation analyzer. The data were entered into a personal microcomputer via an A/D converter and analyzed to obtain the parameters of sound pitch, sound intensity and mean expiratory air flow volume, which were superimposed on the color video monitor screen. PMID- 2214499 TI - Plummer-Vinson syndrome complicated by gastric cancer: a case report. AB - Plummer-Vinson syndrome has been brought to attention as a precancerous lesion of hypopharyngeal and cervical lesions of the esophagus, but that involving the stomach is uncommon. We report a case of Plummer-Vinson syndrome with gastric cancer. A brief literature review of this disorder is presented, and possible causes in this unusual case are discussed. PMID- 2214500 TI - Preliminary study on the microbiology of Campylobacter pyloridis and gastric histopathology. AB - Biopsy samples were taken endoscopically from the antral-mucosa of 693 patients with peptic ulcer and chronic gastritis presenting dyspepsia symptoms. Campylobacter pyloridis cultures were positive in 59 of 98 (60.2%) cases and histopathologically the organisms were found in 411 of 693 cases (59.3%). Pathologically, Campylobacter pyloridis was positive in 273 out of 300 patients with chronic superficial gastritis (91.0%), in 102 of 249 patients with chronic atrophic gastritis (40.9%), in 36 out of 144 patients with chronic atrophic gastritis with intestinalization or dysplasia (25.0%). We found that there was a significant association between the presence of Campylobacter pyloridis and chronic superficial gastritis, also the degree of lymphocyte infiltration showed a strong inverse association with the presence of Campylobacter pyloridis, suggesting that a local immune response might exert an important action in the eradication of this organism. These findings support the view that Campylobacter pyloridis, may be etiologically related to chronic gastritis and peptic ulceration, even though its role still remains to be determined. PMID- 2214501 TI - Surgical treatment of arch-type dissecting aortic aneurysms. AB - We have proposed calling dissecting aortic aneurysm with entry of the dissection in the aortic arch "arch-type". We described the procedures and results of surgery for 12 cases of this disorder. The dissection was localized (type a) in six cases, and extended (type b) in the other six. Seven cases were treated by patch or direct closure of the entry, with one operative death and two later deaths. Five cases were treated by reconstruction of the ascending aorta and the aortic arch with a prosthetic graft, with two operative deaths and one later death. Efforts must be directed towards improving the outcome of the latter operation. PMID- 2214502 TI - Ether lipids in cancer chemotherapy. AB - There is considerable evidence that certain ether lipids such as 1-0-octadecyl-2 0-methyl-rac-glycero-3-phosphocholine represent a new class of antineoplastic agents. These ether lipids have been shown to be cytotoxic for a wide variety of tumors. The site of action of ether lipids appears to be the cell membrane, where they inhibit the biosynthesis of phosphatidylcholine as well as the activity of protein kinase C. However, it remains uncertain that these effects represent the only mechanism for the cytotoxic action of these ether lipids. Further experiments to elucidate the molecular mechanisms of the cytotoxic action of these compounds are necessary. Clinical phase I pilot trials have been completed showing encouraging tumor response in a small number of patients treated. Some of these ether lipids are selectively cytotoxic to leukemic cells sparing of normal cells within a certain dose range. Thus, they are uniquely suitable for purging residual leukemic cells from remission marrow used for autologous bone marrow transplantation. A phase I/II study of autologous bone marrow transplantation in acute leukemia using bone marrow cells treated with ether lipids is in progress. PMID- 2214503 TI - Expression of hepatitis B surface antigen in Chang cells transfected with hepatitis B virus DNA. AB - To investigate hepatitis B virus (HBV) biology in vitro, the transfection of recirculized HBV DNA into Chang cell line was performed. Linear HBV DNA was isolated from recombinant HBV DNA, pHBR105, which includes the whole genome of HBV and was recirculized. Chang cells were transfected with this recirculized HBV DNA by the two different procedures of calcium/phosphate coprecipitation and electroporation. After the transfection, the presence of large nucleated cells with multinuclei and ground-glass cytoplasma were noticed and these cells seemed to proliferate faster than untreated Chang cells. Transient expression of hepatitis B virus surface antigen (HBsAg) was demonstrated in cytoplasma of transfected cells by indirect immunofluorescence. HBsAg was not detected in the culture supernatants by radioimmunoassay. The extra-chromosomal HBV DNA was detected in the transfected cells by both procedures 7 weeks after the transfection by Southern blot analysis but it was lost 4 weeks after that. It was demonstrated that it was possible to transfect Chang cells with HBV DNA and that DNA was functioning to express HBsAg transiently. PMID- 2214504 TI - Assessment of procedures and instruments for intracordal injection: evaluation of the syringe for periodontal ligament anesthesia (CITO JECT). AB - The intracordal injection technique was first introduced by Brunings in 1911. This technique has been accepted as vocal rehabilitation for dysphonia caused by deficiencies of glottal closure. Although various injection materials have been evaluated, the injection procedure itself has not been studied. In this study, we measured the mechanical force required to perform intracordal injection by using a certain amount of substance, when varying the needle size and syringe type. Although a large needle can reduce the mechanical force for injection, leakage from the pinhole can not be prevented. We modified this technique by introducing a CITO JECT, a syringe, which is used for the anesthesia of the periodontal ligament, to perform the collagen injection. With this technique, the mechanical force required for the injection can be reduced to 1/2 to 1/4 of the force by the conventional technique. We conclude that the introduction of this syringe enable us to use the needle with smaller diameter to facilitate the intracordal injection. PMID- 2214505 TI - Family therapy for juvenile delinquents in a reformatory, K-Institute. AB - The number of juvenile delinquents detained by police for shoplifting, glue sniffing, and automobile and bicycle theft reached its highest level in Japan in 1980 since world war II. The incidence of delinquency has fluctuated up and down somewhat between 1981 and 1988 but has remained slightly below the 1980 peak. In 1988 the number of juvenile detainees between the ages of 14 and 18 was 187,172. Juvenile delinquents currently undergoing training and treatment at the K Institute in Kanagawa Prefecture will be discussed. The K-Institute for the training and correction of juvenile delinquents is a public institution which was established in 1900. It has a holding capacity for 100 male offenders. We have interviewing and treating inmates by psychotherapeutic and psychopharmacological methods since 1975. The institute has recently begun to practice a form of inclusive family therapy where the parent comes and stays with the child in the institute for a short period of time. The treatment program has shown a success so that so far none of the participants have returned to the institute, while 30% of non-participants have returned to the institute. PMID- 2214506 TI - [The sequelae of tuberculosis]. AB - During the 20th century, tuberculosis has been the most prevalent and most harmful disease in Japan. Enormous medical researches have ever been performed to conquer the disease. Nevertheless tuberculosis has left various somatic and psychological residues on vast convalescents. On the other hand, researches to conquer tuberculosis have made considerable contribution to other fields of medicine. 1. Somatic and psychological residues on convalescents from tuberculosis. Chest x-ray findings, cardio-pulmonary disturbance, secondary infection, serum-hepatitis due to mass transfusion during the chest surgery, streptomycin-deafness and psychological disorder. 2. Sequelae of phthisiology. a. In the field of basic medicine. Respiratory physiology, immunology and genetic pharmacology. b. In the field of epidemiology. Methodology to control the disease. c. In the field of clinical medicine. Chest x-ray diagnostics, bronchoscopy, thoracoscopy, randomized controlled trial, regimens of chemotherapy, open chest surgery, anesthesiology, treatment of respiratory failure, informed consent, terminal care and cooperative study system. d. In the field of rehabilitation. Medical, vocational and social rehabilitation of the handicapped. e. In the field of public health. Comprehensive control system of the chronic disease. Smallpox has been eradicated, but the elimination of tuberculosis is still far away. Studies as excellent as past ones should intensively be carried out. PMID- 2214507 TI - [Tuberculin skin test among medical college students]. AB - The incidence of active tuberculosis in Japan has markedly decreased in the past few decades. It is also reported that the prevalence of tuberculosis infection in young population has been decreasing in accordance with the decline in the overall occurrence of tuberculosis. The above mentioned facts indicate that the younger population has a greater risk of developing tuberculosis once exposed to tuberculosis infection. Actually, the epidemics of tuberculosis among the adolescent population have often been reported in recent years. We performed a tuberculin skin test on our medical college students, who might be exposed to tuberculosis infection during their student clinical internship, in order to obtain the information about their present status of reaction to the tuberculin skin test. The data obtained from students between 18 and 25 years old were analyzed using Student's t test and Kruskal-Wallis's method. The mean size of erythema in the group of 23, 24 and 25 years old were significantly greater than that in the group of 20, 21 and 22 years olds. Similarly the latter was significantly greater than that in the group of 18 and 19 years olds. Furthermore, it was proven by the Kruskal-Wallis's method that the older a group was, the greater the chance of a large erythema. One explanation for this fact might be a decrease in the prevalence of tuberculosis infection in the younger generation as described above. Another explanation seems to be related to the revision of the Tuberculosis Prevention Law in 1974.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214509 TI - [Determination of the susceptibilities to antituberculosis agents in Mycobacterium avium-Mycobacterium intracellulare complex]. AB - The determination of the susceptibilities to antituberculosis agents in Mycobacterium avium-Mycobacterium intracellulare complex (MAI complex) is influenced by the size of inoculation used in the determination. Such influences differ greatly according to the drugs. By increasing the number of colony-forming units (CFU) of the inoculation to 10(6)-fold, minimal inhibitory concentrations (MICs) of rifampicin and cycloserine have increased only 2-to 3-fold. However, MICs of ethionamide, streptomycin, enviomycin and ethambutol have increased 4-to 9-fold. In contrast, MICs of isoniazid and sulfadimethoxine have increased 30-to 35-fold. Since the determination of MICs of isoniazid and sulfadimethoxine are so greatly influenced by the size of inoculation, the determinations of MICs of these two drugs should be carried out by use of the "actual count" method (6, 7, 9) or the proportion method (8). In the actual count method, the MIC is determined by inoculating 20-100 CFU. The determination of isoniazid susceptibility of M. tuberculosis (H37Rv) was influenced only slightly by the size of inoculation, but that of M. bovis (BCG) was influenced greatly as occurred in the determination of MAI complex strains. PMID- 2214508 TI - [The significance of subpleural mononuclear cell infiltration in the differential diagnosis of pleurisy showing nonspecific histological findings]. AB - To determine whether or not patients who showed abundant lymphocytes in pleural effusion without any specific findings by pleural biopsy could be histopathologically differentiated between those with tuberculous and nontuberculous origin, we reexamined histology of pleural biopsies of all patients whose pleural effusion showed predominantly lymphocytes and did not contain malignant cells from January, 1984 to March, 1989. A total of 45 patients with a nonspecific histology of pleural biopsy were categorized based on their final diagnosis into three groups; tuberculous (n = 20), carcinomatous (n = 10) and nontuberculous, benign pleurisy (n = 15). Pleural biopsy of patients with nontuberculous, benign pleurisy frequently showed band-like infiltration of mononuclear cells in the subpleural adipose tissue (11 out of 15 patients), while the finding was significantly less frequent in those with tuberculous pleurisy (1 out of 20, p less than 0.01) and pleurisy associated with carcinoma (3 out of 10, p less than 0.05). Based on these findings, the presence of band-like infiltration of mononuclear cells in the subpleural adipose tissue in pleural biopsy of patients with abundant lymphocytes in pleural effusion strongly suggests that the pleurisy is nontuberculous origin. PMID- 2214510 TI - [Serum adenosine deaminase (ADA) activity in patients with active pulmonary tuberculosis]. AB - To clarify the immunological aspect of tuberculosis, we investigated serum adenosine deaminase (ADA) activity, T and B cell percentile in total peripheral mononuclear cells, peripheral T cell subpopulation and their relationship with other inflammatory parameters in 20 patients with active pulmonary tuberculosis. Serum ADA activity showed abnormal high level in all patients in nontreated phase with significant regression after three months treatment by anti-tuberculous drugs (P less than 0.05). In addition, significant positive correlation was observed between serum ADA activity and erythrocyte sedimentation rate at 1 hour (r = 0.56). Concerning about peripheral T cell subpopulation studied by two colour flow cytometry with FITC-conjugated anti-CD4 and phycoerythrin-conjugated anti-HLA-DR antibody, there was positive correlation between CD4(-) HLA-DR(+) T cell and serum ADA activity (r = 0.59) without any abnormal frequency of each T cell subpopulation. Additionally, after the treatment of pulmonary tuberculosis, significant increase of T cell percentile in total peripheral mononuclear cells were observed (P less than 0.005). In conclusion, these results may suggest serum ADA activity could be a parameter of activity of pulmonary tuberculosis and reflect the function of activated suppressor/cytotoxic T cell. PMID- 2214511 TI - [An operated case of Mycobacterium fortuitum infection with hemoptysis]. AB - An operated case of M. fortuitum infection on the bronchiectatic lung was presented. A 68-year-old female had had hemoptysis due to bronchiectasis since she was 44 years of age. She had a history of pulmonary tuberculosis at the age of 58 and treated by anti-tuberculosis drugs for a year. She was referred to the National Sanatorium Hiroshima Hospital in March 1986 for surgical treatment, when M. fortuitum infection was found. Lobectomy of the right middle lobe, right S6 Segmentectomy and partial resection of right S2 were performed on December 1st 1986. After the operation, hemoptysis disappeared but M. fortuitum was still found in sputum. Chest X-ray examination revealed some new abnormal shadows. When radical surgical treatment for secondary M. fortuitum pulmonary infection is considered careful attention should be given to its indications including the extent of resection and the predicted post-operative pulmonary function. PMID- 2214512 TI - [Hemolytic activity of Mycobacterium kansasii]. AB - Mycobacterium kansasii has a strong virulence as compared with those of "mycobacteria other than tubercle bacilli". In this study, hemolytic activities of several strains of M. kansasii were investigated. Secretion of hemolytic factor from these strains was not observed, since no hemolytic zone was found around the colonies grown on the 7H11 agar plate when 5% rabbit blood agar was overlayed. On the other hand, weak hemolytic activities were detected after treatment of sonication and trypsin-digestion of M. kansasii cells. They were also heat-resistant. These results indicate that endogenous nonproteinaceous factor was involved in the hemolytic activity of M. kansasii. Moreover, these activities were not species-specific in respect to the kind of target erythrocytes used for the assay. However, hemolytic activity of M. kansasii was not increased in spite of the change of culture conditions or supplement of nutrients into the medium. It is unlikely that this hemolytic activity is directly associated with a pathogenesis of M. kansasii, but detailed studies were needed to clarify on this point. PMID- 2214513 TI - [Bactericidal activities of rifampicin, ethambutol, enviomycin and streptomycin on Mycobacterium avium-Mycobacterium intracellulare complex strains]. AB - Bacteriostatic and bactericidal activities of rifampicin, ethambutol, enviomycin and streptomycin on Mycobacterium avium-Mycobacterium intracellulare complex (MAI complex) strains were determined. The susceptibility testings were made in Ogawa egg medium, and minimal inhibitory concentrations (MICs) were determined as the lowest concentration of drugs, in which the growth of 20 to 100 colony-forming units was completely inhibited. The MICs correspond to the MICs that can inhibit the growth of 95 to 99% of bacterial population. Bactericidal activity was determined in a modified Dubos liquid medium (1.3 g of Dubos TB Broth Base were dissolved in 180 ml of distilled water and this solution was supplemented by 20 ml of bovine serum). A one ml-sample of bacterial suspensions (10 mg wet weight per ml) was added to 9 ml of the Dubos liquid medium, and the medium was incubated at 37 degrees C for 0, 1, 3 and 7 days under shaking condition (56 strokes per minute; 8 cm amplitude). The bactericidal activity was measured as the number of colony-forming units contained in a 0.02 ml-sample of the medium. The bactericidal activities of rifampicin and ethambutol were weak or absent even in strains 13008 and 13016, which were very susceptible to all four drugs. However, the bactericidal activities of streptomycin and enviomycin could be observed in these strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214514 TI - [Present aspect of infection and incidence of tuberculosis in youth registered in Aichi Prefecture]. AB - In this study, 151 school children and students with tuberculosis registered in Aichi Prefecture during 1983 to 1987 were investigated. The results were as follows: 1) The extent of lesions were not so advanced, as shown by the fact that 27.2% were cavitary and 31.8% were bacteriologically confirmed. 2) They were detected mainly by symptomatic visit to physicians (39.1%), periodic mass radiography (31.8%) and contacts survey (20.6%). The proportion of the former symptomatic visit was comparatively lower than in other age groups. 3) Patient's delay in cases detected by symptomatic visit was not so evident, however, there is a certain grade of doctor's delay; for instance, 22.0% of them took 2 months and more to be diagnosed. 4) 77.5% of them were vaccinated with BCG once or more, in most cases more than 5 years before their detection. 5) Sources of infection were specified in 52.3% of the cases. Most of them were found in their household and were bacteriologically confirmed at the time of detection. In some students their classmates were suspected as their possible source of infections. PMID- 2214515 TI - [A case of pulmonary tuberculosis associated with adult respiratory distress syndrome during corticosteroid treatment of rheumatoid arthritis]. AB - We reported a case of 64 year-old female patient of pulmonary tuberculosis associated with ARDS during corticosteroid treatment of Rheumatoid Arthritis. On admission her chief complaints were fever, fatigue and dyspnea. A chest roentgenogram showed diffuse alveolar infiltration consistent with pulmonary edema. Arterial blood gas studies showed severe hypoxemia. We clinically diagnosed so-called ARDS. Smears of sputum for acid fast bacilli were negative, but transbronchial lung brushing by bronchofiberscope revealed many acid fast bacilli. Intensive therapy with anti-tuberculosis drugs (INH, RFP, SM), high dose corticosteroid (methylprednisolone) therapy and mechanical ventilation was started. During the following 2 weeks, the PaO2 rose gradually and the alveolar infiltration on the chest roentgenogram disappeared. The experience of this case to emphasized the importance of suspecting this condition because pulmonary tuberculosis is a potentially curable cause of ARDS and it should also be emphasized that the good treatment effect could be expected with combined use of high dose corticosteroid and mechanical ventilation. PMID- 2214516 TI - The good, the bad, and the ugly. Nursing continuing education: a providers perspective. PMID- 2214518 TI - [Heart murmurs in Sneddon's syndrome]. PMID- 2214517 TI - [Early ventricular repolarization syndrome in diseases of the cardiovascular system]. PMID- 2214519 TI - [Association of coronary atherosclerosis, congenital coronary fistulas and Fallot's triad in a middle-aged man]. PMID- 2214520 TI - [Case of latent Wolff-Parkinson-White syndrome with various supraventricular arrhythmias]. PMID- 2214521 TI - [Intravital diagnosis and successful surgical treatment of cardiac rhabdomyoma]. PMID- 2214522 TI - [Long-term monitoring of blood pressure]. PMID- 2214523 TI - [Metabolites of anti-arrhythmia agents, their pharmacodynamics and pharmacokinetics]. PMID- 2214524 TI - [Disorders of hemodynamics and pulmonary gas exchange in the acute period of myocardial infarct]. AB - In 40 patients with massive myocardial infarction, the central hemodynamics was examined by probing the right-sided chambers of the heart and the pulmonary artery. The cardiac output was measured by thermodilution. The gas exchange (respiratory minute volume, capnography, gas analysis of arterial and mixed venous blood) was explored. Arterial hypoxemia was found to be associated with increased intrapulmonary blood shunting in patients with acute myocardial infarction complicated by congestive heart failure. Deterioration of arterial hypoxemia was promoted by a combination of increased overall pulmonary shunting and decreased residual venous oxygenation. Abnormalities in the ventilation perfusion relations are of great importance. PMID- 2214525 TI - [Primary angina pectoris: significance of clinical, bicycle ergometric and coronarographic data in the prognosis of ischemic heart disease remission]. AB - By the first year of a follow-up, spontaneous clinical remissions (no anginal and ischemic episodes as evidenced by Holter monitoring, negative bicycle ergometric tests) in 52 (26%) out of 200 patients with primary angina pectoris. Possible predictors such as clinical signs, bicycle ergometric and coronary angiographic parameters were examined. A multifactorial stepwise discriminant analysis showed that the independent predictors of the clinical remission were heart rate and exercise power attained on bicycle ergometry, number of diseased coronary artery segments with 70% of more stenoses, disease pattern in the first month, existing and prior smoking, and myocardial infarction in the first 3 months of the disease onset. PMID- 2214526 TI - [Hemodynamics and its control in patients with thyrotoxicosis and in healthy persons according to the data of anapriline and graded exercise tests]. AB - The study was undertaken to examine effects of anapriline on bicycle ergometric and echocardiographic parameters and catecholamine excretion in 17 patients with thyrotoxicosis and 21 healthy subjects. A single dose of anapriline contributed to transition of hyperkinetic central hemodynamics to eukinetic one and a more saving regimen of heart performance at rest and submaximal exercise levels in the healthy subjects. In contrast, the patients maintained hyperkinetic hemodynamics and had a high energy demand during exercise and showed a reduction in left ventricular systolic and diastolic function and a significant decrease in catecholamine excretion. Disintegration of regulatory mechanisms in thyrotoxicosis was found to be due to the function interrelationship between thyroid hormones and catecholamines. PMID- 2214527 TI - [Comparative analysis of the significance of transesophageal stimulation of the left atrium and bicycle ergometry in the detection of residual myocardial ischemia during the early period of myocardial infarct]. AB - The study was undertaken to compare transesophageal left atrial pacing (TLAP) and bicycle ergometry (BE) in the detection of residual myocardial ischemia (RMI) in 187 patients with myocardial infarction in the early periods of the disease (on days 20 to 26). The intensity of TLAP and BE was increased up to the threshold and submaximal levels according to the conventional criteria. Among the patients, RMI was detected in 71% with TLAP and in 55% with BE (p less than greater than 0.01). Thus, this suggests that TLAP has advantages over BE in the detection of RMI in patients with myocardial infarction in the early periods of the disease. PMID- 2214528 TI - [Anaerobic threshold levels in the assessment of central and peripheral hemodynamics]. AB - A treadmill test involving a noninvasive evaluation of cardiac pump function and the anaerobic threshold (AT) was performed to examine 110 patients with cardiac malformations, 31 with atherosclerotic lesions in arteries of the lower limbs, and 49 normal subjects. The results were compared with those of direct measurement of blood lactate concentrations. Simultaneously, changes in transcutaneous O2 tension (TcpO2) were recorded in the recovery periods after each exercise stage, recovery of continuous blood flow (td). TcpO2 and td were indicated to reflect AT resulted just from decompensation of cardiac pump function in patients with impaired central hemodynamics. It was ascertained that TcpO2 and td might be objective measures for severity of central or peripheral hemodynamic abnormalities and reflected the levels of AT at systemic, organic, and microcirculatory levels. PMID- 2214529 TI - [Significance of visual-scanning Doppler detection in the diagnosis of early stages of cardiac insufficiency in patients with ischemic heart disease]. AB - A method was developed for visual monitoring myocardial structures in the mode of continuous Doppler location by using a commercial Soviet device. The method proposed measures the velocity of mobility of well-defined cardiac structures. Clinical examinations showed that myocardial contractile abnormalities could be detected earlier by visual-prospecting Doppler echocardiography than by routine Doppler location and echocardiography. The IVth standard location position is the most informative in the detection of impaired contractility. When the Doppler echocardiogram in the first additional position is analyzed, the appearance of P wave may serve as a reliable criterion for diminished myocardial contractility. PMID- 2214530 TI - [Body impedance recording in the assessment of stroke volume]. AB - The first derivative of the integral tetrapolar rheogram of the body, body impedance recording, was found to show changes in blood flow in the arterial compression chamber. Evidence was given for a close relation of the distance between the electrodes while recording an integral rheogram of the body and the examinees' height. The relation of the distance to the examinees' height was equal in males and females and proved to be lower than that previously applied. For calculation of the stroke blood volume from the body impedance recording, the Kubicek equation was proposed to be used by introducing the height of an examinee instead of the distance between measuring electrodes. There was a good coincidence of results while calculating the stroke volume by impedance recording and Doppler echocardiography. PMID- 2214531 TI - [Use of coronary thrombolysis and coronary balloon angioplasty in patients with myocardial infarct]. PMID- 2214532 TI - [Relations between the duration of coupling interval and frequency fluctuations in ventricular ectopic complexes]. AB - An attempt was made to electrocardiographically assess the likely mechanisms responsible for the occurrence of arrhythmias. The frequency of ventricular ectopic complexes was compared with fluctuations of coupling interval duration. An examination of 36 patients provided evidence for preliminary considerations concerning the causation between the frequency of ventricular ectopic complexes and the duration of coupling interval. The findings are promising from clinical and predictive points of view. PMID- 2214533 TI - [Criteria for a pathogenetic approach to antiarrhythmic therapy in paroxysmal supraventricular reciprocal tachycardia]. AB - An electrophysiological study using programmed transesophageal atrial pacing was performed in 106 patients with abnormalities in the myocardial conduction system, of whom 102 suffered from paroxysmal supraventricular reciprocal tachycardia and/or paroxysmal atrial fibrillation. The electrophysiological properties of the myocardial conduction system were demonstrated to be labile. The factors determining the frequency and length of palpitations were outlined. The conditions for an onset of supraventricular reciprocal tachycardiac paroxysm and for existence of a reentrant chain were found to be minimal in the effective refractory period of the accessory pathway, which was less or equal to the effective refractory period of the atrioventricular junction. An approach to antiarrhythmic therapy was proposed, which was based on modifying the ratio of the effective refractory periods of normal and abnormal excitation pathways. PMID- 2214534 TI - [Experience with long-term outpatient use of cordarone in the prevention of paroxysms of atrial fibrillation (flutter)]. AB - In a group of 250 patients suffering from frequent paroxysms of atrial fibrillations (flutters), the application of cordarone for 1 to 5 years prevented the occurrence of arrhythmic paroxysms in 23.6%, contributed to a reduction of their numbers up to 1 a year in 35.6%, up to 2-3 a year in 20.4%. Good and satisfactory results were obtained nearly in 80% of the patients. Cordarone failed to act in 10.4%. In 12.8%, the "escape" phenomenon was observed, i.e. loss of the agents' action following its long-acting effect when the patients were on a maintenance dosage. The results of the preventive usage of cordarone were not clearly related to the degree of atrial dilatation and the pattern of cardiac disease. PMID- 2214535 TI - [Functional state of atrioventricular conduction and inducibility of atrioventricular reciprocal tachycardia]. AB - Programmed transesophageal electrical stimulation was used to examine 733 rural inhabitants aged 16 to 70 years. Conduction dissociation along the atrioventricular node was revealed in 65 (8.8%) of the examinees, out of them 12 had induced paroxysms of atrioventricular nodal tachycardia. Atrioventricular tachycardia involving the accessory anomalous pathways was provoked in 10 subjects. Among them 2 had apparent, 1, latent, and 7, obscure forms of the Wolff Parkinson-White syndrome. The induced paroxysms of atrioventricular tachycardias were sustained in 45.5% of the cases. Only 50% of the subjects had clinical signs of tachycardia in their medical histories. PMID- 2214536 TI - [Chronic nonparoxysmal supraventricular tachycardia in children and adolescents]. AB - An examination was performed in 111 children and adolescents with recurrent and sustained chronic nonparoxysmal tachycardias (CNPT). ECG and electrophysiological studies showed that ante- and retrograde conduction along the accessory atrioventricular junction was the most common mechanisms of arrhythmia. Holter monitoring revealed a high rigidity of cardiac rhythm in patients with sustained CNPT. Criteria for the development of arrhythmogenic cardiac dilatation were developed. In recurrent CNPT, there was a correlation between the paroxysms of ECG slow-wave activity and the "salvos" of tachycardia and a predominance of vagal effects on the heart. A new approach to the treatment of children with CNPT was proposed, which involved the correction of pathogenetic mechanisms. Indications for the usage of antiarrhythmic agents such as cordarone and a cardiac surgeon's advice were formulated. The efficiency of the therapy was achieved in 82% of the children as shown by a follow-up. PMID- 2214537 TI - [Disorders of myocardial metabolism in sudden coronary death in the presence of coronary atherosclerosis: findings of quantitative histoenzymologic studies]. AB - The activity of human myocardial enzymes in sudden coronary death (SCD) was quantitatively histochemically examined. The activity of succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), beta-oxybutyrate dehydrogenase (beta-OBDH), alpha-glycerolphosphate dehydrogenase (alpha-GPDH), NAD-diaphorase (NAD-ase), and glucose-6-phosphate dehydrogenase (G-6-PDH) was measured on prompt autopsies (up to 3 hours of death onset). beta-OBDH and LDH showed an increase in activity in the myocardium from the subjects who had suddenly died from coronary heart disease without evident changes in the heart. In SCD in the presence of small cardiosclerosis, the activity of the enzymes characterizing the major processes of energy generation was also enhanced, which was caused by moderately severe myocardial hypertrophy. In the myocardium from the subjects who had died from coronary heart disease in the presence of large postinfarction cardiosclerosis, the activity of the enzymes was directly related to the degree of myocardial hypertrophy and the signs of chronic heart failure. As myocardial hypertrophy progressed, the enzymatic activity rose, but there were signs of chronic heart failure, it fell. The findings suggest that the changes in myocardial enzymatic activity in SCD are heterogeneous and associated with the type of prior abnormalities in the cardiovascular system. PMID- 2214538 TI - [Several aspects of early ventricular repolarization syndrome]. AB - An epidemiological study was undertaken to examine the prevalence of the early ventricular repolarization syndrome (EVRS) among 3,105 subjects. An analysis was made of 796 ECG showing EVRS. The genesis of EVRS was interpreted in terms of vector-scalar and chronotopographic analyses of myocardial de- and repolarization. The syndrome was also characterized from clinical and electrophysiological points of view. PMID- 2214539 TI - [Early ventricular repolarization syndrome in patients with heart defects]. AB - The prevalence of the early ventricular repolarization syndrome (EVRS) was examined in 129 patients with congenital and acquired heart diseases. Dynamic ECG values were assessed. The most prevalence rate was found in patients with congenital heart disease (100%), aortic (80%), mitral (51%), and aorto-mitral valvular (60%) diseases. The prevalence of EVRS, the mechanisms of its occurrence were associated with the performance of accessory pathways and the manifestation of the competitive nature of the functional interaction between the basic and accessory pathways. PMID- 2214540 TI - [Ultrasonic diagnosis of congenital membraneous subvalvular aortic stenosis]. AB - The paper reviews a 10-year experience with complex ultrasonic diagnosis of membraneous subvalvular aortic stenosis, a rare congenital defect. Fifteen subjects operated on for this abnormality were examined. Profound systolic closure of the aortic cusps, concentrated left ventricular myocardial hypertrophy, linear-shaped echo signals generated by the membrane in the subaortic area, turbulent systolic blood flow in the ascending aorta are the most significant signs for the diagnosis of the membraneous subvalvular aortic stenosis. PMID- 2214541 TI - [Role of genetic and environmental factors in the determination of body weight and skinfold thickness in children having different blood pressure (a familial study)]. AB - Based on intrafamilial correlations, a component genetic analysis was used to evaluate the contribution made by genetic and environmental factors to variance in body weight and skin fold thickness in children who had various blood pressure. In children with initially elevated and normal blood pressures, the phenotypic variation in the body weight and adipopexia is largely determined by genetic factors, whereas in those with initially lower blood pressure, the phenotypic variation in the above parameters is greatly affected by environmental factors, mainly by those of occasional nature. The findings provide evidence for a differential approach to the primary prevention of hyper- and hypotension in children and adolescents. PMID- 2214543 TI - [Entropy of heart rhythm, one of the parameters of a rhythmogram, in the clinical evaluation of patients with chronic ischemic heart disease]. PMID- 2214542 TI - [Evaluation of the effectiveness of thrombolytic therapy using streptodecase in patients with myocardial infarct]. PMID- 2214544 TI - Update on vitamin D: 1990. PMID- 2214545 TI - New active analogues of vitamin D with low calcemic activity. AB - In conclusion, a number vitamin D analogues have been developed that have very low calcemic activity but retain several other properties of 1,25-(OH)2D3, including the ability to differentiate leukemia and skin cells, to enhance the immune response, and to suppress parathyroid hormone levels. Although the mechanism of this selective activity is not yet clear, these analogues may provide new insights into the differences in action of 1,25-(OH)2D3 in various target tissues. Most importantly, the selective action of these analogues may be exploited for the treatment of diseases such as leukemia, psoriasis and hyperparathyroidism. PMID- 2214546 TI - Extrarenal production of calcitriol. AB - Under normal circumstances extrarenal sources of calcitriol probably constitutes a microendocrine system involved in cell differentiation and local intercellular communication with no influence on systemic calcium homeostasis. Under pathological conditions such as chronic renal failure, extrarenal sources have the potential to normalize serum calcitriol after adequate stimulation (such as, 25(OH)D administration). Extrarenal 1,25-(OH)2D3 synthesis is controlled by physiological levels of calcitriol. However, in sarcoidosis and other granulomatous diseases, 1,25-(OH)2D3 production by macrophages is deregulated, causing severe alterations in systemic calcium homeostasis. PMID- 2214547 TI - Effects of 1,25(OH)2D3 administration on bone in patients with renal failure. PMID- 2214548 TI - Use of oral and parenteral calcitriol in the treatment of renal osteodystrophy. PMID- 2214549 TI - Parathyroidectomy in chronic renal failure: indications, surgical approach and the use of calcitriol. AB - The appropriate use of phosphate binders, calcium supplements and especially calcitriol therapy has significantly decreased the incidence of overt secondary hyperparathyroidism in dialysis patients. Nevertheless some patients may still need parathyroidectomy, especially in the event of severe clinical signs and symptoms such as persistent hypercalcemia, pruritus, calcifilaxis, or extensive extra-skeletal calcification. Since aluminum-induced bone disease may resemble hyperparathyroidism in dialysis patients, whenever parathyroidectomy is contemplated the diagnosis of secondary hyperparathyroidism must be firmly established. Thus, a bone biopsy is mandatory prior to parathyroidectomy. It is our experience that once the patient goes to surgery the most important factor in the surgical approach is the presence of a skilled surgeon who has extensive experience in parathyroid gland surgery. The data comparing subtotal parathyroidectomy with total parathyroidectomy and autotransplantation are similar. The most important shortcoming is the lack of long-term follow-up. Recently, new data by several investigators has been advanced reintroducing total parathyroidectomy. Long-term observations in patients who despite total parathyroidectomy still have normal PTH levels are of special interest. In addition, long-term follow-up of these patients has shown that normal plasma calcium and phosphorus levels may be maintained without the use of Vitamin D; this occurred in the presence of active mineralization. However, our major objection to this procedure is the risk of aluminum-induced bone disease. At the present time we feel that the relative high incidence of recurrent hyperparathyroidism following subtotal parathyroidectomy is a reasonable trade off for the risk of aluminum bone disease which may develop in absence of PTH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214550 TI - [Micturition and urinary tract infection in girls. 4. Various aspects of age factors]. AB - First affection with urinary tract infection, relapses, and micturition pattern were analyzed depending on age. It is demonstrated that the decreased UTI rate after the 12th year rather depends on the micturition habit than on puberty. PMID- 2214551 TI - [Sonographic diagnosis of gastroesophageal reflux in infancy]. AB - The gastroesophageal reflux is a common problem in the pediatric clinical practice in the 1st year of life. Its diagnosis is mainly based on the x-ray and the measurement of the esophageal pH. Our investigation shows the possibility of the ultrasonographical diagnosis of this disturbance. We could demonstrate a good correlation between the x-ray and the ultrasonographical findings. A continuous lasting gastroesophageal reflux which takes more than 5 minutes points to a pathologic reflux pattern with the well known complications. Thus, ultrasonographical investigation should perform before an extensive diagnostic is taken into consideration. PMID- 2214552 TI - [Diagnostic evaluation of skeletal scintigraphy in comparison to roentgen studies in histiocytosis X in childhood. Case report]. AB - We have compared whole body skeletal scintigraphy with X-ray examination in 15 children suffering from histiocytosis X, 14 of whom also showed involvement of the skeleton. In 9 of 20 cases, relapses, included, involvement of the skeleton was found both in scintigraphy and X-ray examination. In 7 cases only X-ray examinations have revealed lessons, which could not be proved by scintigraphy. Vice versa, in 4 cases scintigraphy was positive alone. These results confirm the necessity to use both methods for an exact documentation of the extent of the disease before undertaking any therapy. Dispensing with one of the two methods may cause incorrect therapeutic decisions and increase the risk of relapses and late complications. PMID- 2214553 TI - [The differential diagnosis of hemarthrosis--septic arthritis in patients with hemophilia]. AB - A 12-year-old boy with severe hemophilia A fell ill with high fever and painful swelling of joints. There was a delay of four days in the diagnosis of septic arthritis. The course of the disease shows some important distinguishing criteria, speaking in favour of septic arthritis: 1. longlasting temperature above 39 degree C; 2. an elevated peripheral leukocyte count; 3. increasing complaints despite normalisation of the coagulation defect. PMID- 2214554 TI - [Social indication for hospitalization. Annual analysis of the pediatric department of the Magdeburg district hospital]. AB - The patients' data of 156 children hospitalized on account of social indication were analysed at the Clinic for Pediatrics of Magdeburg District Hospital. Reasons for socially indicated hospitalization were: proved or imminent neglecting of children (49%), insufficient nursing of sick children (31%), suspected ill-treatment (8%), serious family troubles temporarily preventing nursing and safety of children (12%). Neglected hygienic condition of the body, improper nutrition of malnutrition, physical and mental lagging behind might be evidence for the social sufferings of children. Mothers of children obtaining in patient treatment as a result of social indication predominantly lack lasting partnerships. They are Less qualified concerning vocational training or gave birth to their first child at a comparatively early age. There is an urgent necessity of closely cooperating between the Clinic for Pediatrics, the Maternity Advisory Centre, the Youth Well-Fare Service and the Department of Youth-Well Fare in order to detect the children concerned in time to be able to find the best possible solution for the future life of the children without delay. PMID- 2214556 TI - [Transplantation of immature allogeneic testis]. AB - Experimental and clinical studies (109 rat and 17 dog experiments and four clinical transplantations of a neonatal testis to children with the postcastration syndrome and postnatal hypoplasia of their own testes) showed that transplantation of an immature testis makes it possible to reduce to maximum its damage on exposure to the effect of unspecific and specific factors of transplantation. The transplantation ensures prolonged viability and function of the allogeneic male sexual gland, which is confirmed by the maintenance of its specific structures (the ultrastructural level among others) in the late-term postoperative period, the ability of immature allogeneic transplants to restore the sexual behaviour of castrated animal recipients, and by the positive results of clinical test of the method. PMID- 2214555 TI - [Use of Nichrome suture material]. AB - The suture material and the method of its application play an important role in the prevention of wound complications. With the use of Nichrome wire thread as the suture material in surgical interventions, the number of postoperative complications significantly was decreased. The Nichrome thread is also used expediently in operative interventions on patients with purulent diseases of the soft tissues, including cases after primary surgical treatment of purulent foci by carbon dioxide laser. PMID- 2214557 TI - [Treatment of diabetic angiopathies of the lower extremities]. AB - Patients with diabetes mellitus accounted for 7% of all hospitalized patients. The authors analyse the treatment of 126 patients in whom diabetes mellitus was complicated by angiopathies of the lower limbs. Patients over 60 years of age accounted for 60.3% of cases. Concomitant diseases were found in 87 patients. The article shows the main principles of the complex management of patients, which is based on correction of carbohydrate and other types of metabolism, treatment of concomitant diseases, and timely operation. When surgery was necessary in stage IV of the disease, preference was given to economical operations. It is shown that if amputation of the limb cannot be avoided, an effort should be made to preserve the knee. The mortality rate was 10.3%. PMID- 2214558 TI - [Treatment of patients with nodular goiter]. AB - The authors discovered nodular patterns in the thyroid gland of 18.8% of persons among many thousands subjected to periodical medical examination. The high detection rate of nodular patterns in the thyroid corresponds completely to the findings of post-mortem examinations. The number of nonpalpable nodules detected by the ultrasonic method exceeds the number of those palpated (55.2% and 44.8%, respectively). Ultrasonic examination with thin-needle aspiration biopsy followed by cytologic examination is the most informative method by which new malignant growths are identified. Patients with nonpalpable patterns measuring less than 1 cm in diameter which are revealed by ultrasound must be kept under active dynamic observation if there are no signs of malignancy. Patients with larger patterns and suspected cancer must be treated by operation. PMID- 2214559 TI - [Activation of immunity in patients with recurrent goiter]. AB - The authors studied the morphological pattern of the thyroid gland in patients with goiter and in those with a recurrence of the disease. They found lymphoid infiltration and autoimmune thyroiditis twice more frequently in patients with recurrent goiter. Dynamic study of features of the immune and thyroid status of patients with recurrent goiter after the operation led to the isolation of a group of patients with an increase in the relative content of T and B lymphocytes and thyroxine. These changes preceded the recurrence of goiter. PMID- 2214560 TI - [Laboratory and instrumental diagnosis of echinococcosis during conducting mass screening and surgical treatment]. AB - In the course of 15 years the authors conducted a comprehensive examination of over 13,000 patients for establishing the diagnosis and surgical treatment of hydatid disease; among these patients there were more than 3,000 who underwent operation, 1,280 who were examined for recurrence of the disease, and 5,000 who were subjected to periodical medical examination. The enzyme immunoassay and indirect hemagglutination test are the most reliable in the diagnosis of primary and recurrent hydatid disease and in periodical examination; the latex fixation test remains false-positive (16.9%) up to 3 years. Combination of laboratory and instrumental methods (computed tomography, ultrasonic examination, scanning and multi-view X-ray examination) makes it possible to establish not only the topical diagnosis but also the state of the hydatids, which helps in the choice of the operative method. PMID- 2214561 TI - [Oblique terminal-lateral gastroduodenoanastomosis in surgery of stomach ulcer]. AB - The authors analyse the results of surgical treatment of 316 patients with peptic ulcer after gastric resection completed by the formation of terminolateral gastroduodenoanastomosis after the Haberer-Finney techniques. In 189 patients vagotomy was carried out in addition to the operation. The postoperative mortality rate was 0.3% (due to incompetence of the sutures of the anastomosis). The incidence of nonfatal complications was 9.4%. The late-term results were good (according to Visick's grading) in 98.65% of patients. PMID- 2214562 TI - [A device for irrigation of suppurative cavities]. PMID- 2214563 TI - [Combined injuries of the organs of the small pelvis and abdominal cavity]. PMID- 2214564 TI - [Migration of foreign body from the small pelvis through the organs of the urinary system]. PMID- 2214565 TI - [Adenocarcinoma of the cecum simulating acute appendicitis]. PMID- 2214566 TI - [Diagnosis and surgical treatment of hepatic hemangioma (review of the literature)]. PMID- 2214567 TI - [Results of clinical and experimental use of cyclosporin A (review of foreign literature)]. PMID- 2214568 TI - [Changes in acid-base equilibrium of blood after intravenous laser irradiation (experimental study)]. AB - Experiments were conducted to study the acid-base equilibrium of blood in pancreatitis and in combination with laser irradiation of venous blood by the intravascular method through a light guide. Irradiation of blood was attended by inhibition of metabolic acidosis development, which was evidently linked with improved blood oxygen transport function in response to exposure to the laser beam. PMID- 2214569 TI - [Treatment of fissure in ano by the method of laser coagulation]. AB - The article analyses the results of treatment of acute and chronic anal fissures with the use of the method of laser photocoagulation in 181 patients, in 87 of them the fissures were combined with other proctological diseases. The essence of the operation is three-fold laser treatment (CO2 laser) of the edges and floor of the fissures. The pathologically changed tissues are evaporated and coagulated in this case with the formation of a coagulation film on the wound surface. Histological examination of bioptic material collected from the zone exposed to the effect of the laser shows complete disappearance of the pathological tissue. The operation is simple and sparing in the treatment of anal tissues, ensures improvement of the immediate results, as well as a decrease of the frequency of a recurrence to 1.4%. The method may be introduced successfully into outpatient surgical practice. PMID- 2214570 TI - [Use of laser irradiation in the complex ambulatory treatment of arthrosoarthritis]. AB - The article discusses experience with the treatment of 60 patients with arthrosoarthritis deformans of various large joints by the traditional conservative methods and with the use of laser radiation by an Uzor biomedical laser device. The authors noted a positive effect of laser radiation on the pathological processes developing in the region of the involved joint, which reduced the terms of treatment from 24.4 to 10.4 days and considerably reduced the number of recurrences in the immediate period. PMID- 2214571 TI - [Surgical debridement of gunshot wounds]. AB - The authors conducted experimental (130 rabbits) and clinical studies (249 persons) in gunshot wounds of the soft tissues. It was found that in 29% of cases, primary surgical debridement of the gunshot wound failed to be a radical intervention because zones of secondary necrosis of the tissues developed on days 3-4. In view of this, gunshot wounds must be examined without fail on days 3-5 to determine the indications for repeated surgical debridement. The indications for repeated surgical debridement are as follows: foci of necrotic tissues, unopened pockets, the presence of foreign bodies. Repeated surgical debridement of a gunshot wound, when indicated, reduces the number of purulent complications by 4 times and the duration of treatment by 1.5 times. PMID- 2214572 TI - [Laser surgery in occlusive diseases of peripheral arteries]. AB - The first experience with the use of an excimeric laser in the treatment of 24 patients with segmental occlusion of the peripheral arteries is discussed. It proved possible to recanalize the obstructed segment of the vessel for its whole distance in 13 patients. Analysis of the complications shows that further technological development of the method is necessary. Hemodynamic adequacy of restoration of the vascular lumen by laser recanalization in combination with balloon dilatation is demonstrated. Significant decrease of the risk of operative intervention, accelerated rehabilitation of patients, and an essential economical effect may be the advantages of the method. PMID- 2214573 TI - [Treatment of patients with thermal lesions with ointments on water-soluble base]. AB - Treatment of patients with thermal burns by ointments prepared on a water-soluble base (Dioxidine and Dioxicol) makes it possible to reduce the bacterial dissemination within a short time and prepare the wound for autodermoplasty which, in turn, reduces the danger of the development of infectious complications. In addition to a marked antimicrobial effect, the ointment possess high hydrophobic and hydrophilic properties and do not induce allergic reactions and side effects. PMID- 2214574 TI - [Pathogenetic mechanisms of the effect of vacuum therapy on the course of the wound process]. AB - On the basis of the analysed results of treatment of 248 patients with abscesses, phlegmons, and purulent wounds who received vacuum therapy and 215 patients with the same diseases treated by the traditional incision-drainage-method, as well as on the grounds of additional examination findings, the authors show the mechanisms of the effect of vacuum therapy on the course of the wound process. They substantiate pathogenetically the marked therapeutic effect of this method in patients with acute purulent diseases of the soft tissues and purulent wounds. PMID- 2214575 TI - [Clinical significance of non-fermentative bacteria isolated from the environment of a surgical department]. AB - The article deals with the frequency of isolation of non-fermentative gram negative bacteria, potential causative agents of postoperative infection, from objects found in the environment of various departments of a surgical inpatient clinic. The species composition of the grown culture was determined. The relation of the isolation rate of certain species of nonfermentative bacteria to the object of the examination, the department of the clinic, and the disinfection method applied was revealed. The authors point out that it is necessary to undertake systematically the investigations to determine of the activity of antiseptics and disinfectants in relation to the microorganisms indicated in order to choose the effective methods for the prevention of postoperative infection induced by nonfermentative bacteria. PMID- 2214576 TI - [Active methods of correction of endotoxemia in generalized suppurative infection]. AB - The characteristics of the natural history of acute sepsis and the nature of the intoxication syndrome are analysed an on ample material (120 patients), and microbiological and immunological diagnostic findings are shown. Endotoxicosis in sepsis is attended by marked disorders of the immune status in the form of varying degrees of immunodeficiency. The authors generalize their experience with the management of endotoxicosis in sepsis. The article first shows the results of the combined use of various methods of endotoxicosis correction (homosorption, hemodiafiltration, plasmapheresis, endolymphatic therapy, ultraviolet irradiation of autoblood, hyperbaric oxygenation, application sorption) in the treatment of 120 patients with sepsis of various etiology. Active methods of detoxification via the blood and lymphatic system were first applied in the management of endotoxicosis in patients with sepsis. PMID- 2214578 TI - [Surgical treatment of phlegmons of the maxillofacial region]. AB - A method was developed for active surgical treatment of phlegmons of the maxillofacial region with the application of intraarterial regional drug therapy. The suggested method was used in operations on 75 patients. The results were compared with those in 65 patients who were treated by the traditional method- opening of the phlegmon. In 95.7% of patients in whom the active method of surgical treatment was applied, the postoperative wound healed by first intention. The treatment produced the best clinical and aesthetic effect. The period of incapacity of the patients reduced almost by half. PMID- 2214577 TI - [Lipid regulation in suppurative infectious diseases]. AB - The paper discusses the results of study of lipid peroxidation (LP) in patients with various forms of purulent surgical infection. A conclusion is drawn from the analysis of the obtained data that the difference in the forms of the pyoseptic processes is determined to a great measure by the concrete state of free-radical lipid oxidation which acts as a regulatory mechanism of the inflammatory reaction, changing the permeability of biomembranes at the tissue, cell, and organism levels. The conducted research holds promise for the creation of modern and progressive variants of pathogenetic intensive therapy. PMID- 2214579 TI - [Free transplantation of skin flaps with axial blood supply in IV degree burns]. AB - The article analyses the results of free transplantation of skin grafts with axial blood supply in 45 patients with IV degree burns and their sequelae. Bearing in mind the peculiarities of damage to the tissues and vessels in a thermal trauma, it is advisable to anastomose the vein grafts with the large subcutaneous veins. Skin grafts with a long vascular pedicle are preferable. The difficulties which are encountered in the choice of the surgical tactics and in planning the operative intervention in patients with multiple areas with IV degree damage or their combination with extensive III degree burns insistently dictate the need for stricter indications for microsurgical transplantations, and rational and substantiated combination of plasty by free grafts and skin flaps with an axial blood supply type. PMID- 2214580 TI - [Cutaneo-fascial flaps in restorative and reconstructive surgery of burns]. AB - On the basis of experience with the treatment of more than 1,500 patients with post-burn defects, deformities, and trophic ulcers, the authors distinguished types of affection in which the traditional methods are ineffective. These 133 patients were subjected to plasty with ++cutaneo-fascial grafts; the zones of donor areas from which the grafts are taken are determined. Plasty with ++cutaneo fascial grafts is indicated in defects of the face, deformity of the neck, total adduction contracture of the arm, defect of the breast, and affections of the hand, leg, and foot. Concrete grafts and the site from which they are taken for restoration of certain regions of the body are suggested. ++Cutaneo-fascial grafts make it possible to restore the shape, function, and the skin of the involved region. PMID- 2214581 TI - [Surgical treatment of extensive and deep defects of crural soft tissues using the gastrocnemius muscle and skin flaps]. AB - The article discusses a method for surgical treatment of extensive and deep defects in the soft tissues of the leg by plasty with a gastrocnemius musculocutaneous graft taken from the contralateral limb. The operation was conducted in two stages. It is emphasized that if all the described technical details are followed, the postoperative period will be uncomplicated and the outcome of the operation will be good. PMID- 2214582 TI - [Treatment of pustular lesions of the perineum and sacrococcygeal region]. AB - The results of treatment of 316 patients with chronic pustular lesions of the perineum and sacrococcygeal region are discussed. It is shown that the only radical measure in this category of patients is total excision of the involved tissues and, in combined variants, simultaneous performance of typical operations for rectal fistula or coccygeal pilonidal fistula. In localized and mostly in regional forms of the disease one-stage surgical interventions are expedient. Many-stage operations are indicated in extensive and, less frequently, in regional forms. Postoperative complications occurred in 5.3% of cases and were associated with wound suppuration. The late-term results were studied in 71.7% of patients who underwent operation: recurrences developed in 3.7% of cases. PMID- 2214583 TI - [Guided punctures in the treatment of hepatic and perihepatic abscesses under ultrasonic control]. AB - The authors discuss the possibilities of ultrasonic tomography and subsequent performance of purposeful punctures for establishing the precise diagnosis of hepatic and perihepatic abscesses. In most cases the method helps in revealing the cavities measuring no more than 1.5-2.0 cm. The indications are determined, as well as the techniques of topical treatment with the use of single and multiple punctures and prolonged percutaneous drainage. Seventy-three patients (32 with hepatic and 41 with perihepatic abscesses) underwent clinical examination. Topical therapy was applied in 21 patients with discovered hepatic abscesses, 17 of them recovered. Operations were avoided in 25 in a group of 34 patients with perihepatic abscesses (in 7 the abscesses were not identified). The success of this treatment is determined by exact diagnosis and precise manipulations. PMID- 2214584 TI - [Evaluation of the adequacy of heparin administration during hemosorption]. AB - The article discusses the results of using the activated coagulation time in hemosorption for the first time to determine the level of heparinization in 60 patients with obstructive jaundice and myasthenia++. The method made it possible to control the blood heparinization level during hemosorption, reduce the dose of heparin administered before the perfusion to 1.2-1.5 mg/kg, prevent the development of thrombosis in the mass exchanger and, simultaneously, avoid the neutralization of heparin with protamine sulphate. PMID- 2214585 TI - [Changes in immunological indicators in patients with surgical endotoxemia after UV-irradiation of blood]. AB - Changes in the values of the immune status during UV autohemotherapy were studied in 22 patients with surgical endotoxicosis of various genesis. Maximum tension of immunogenesis was found in all patients. The time course of changes in the general pool of rosette-forming and separate populations of neutrophils, as well as in the index of immunocompetent cell ratios are evidence of the high informativeness of these tests in determining the severity of the immune system dysfunctions. PMID- 2214586 TI - [Comparative evaluation of various methods of initial hypothermic perfusion of donor kidneys]. AB - The authors discuss three various methods of initial hypothermic perfusion applied in 160 donors. The function of the donor kidneys was evaluated according to the results of clinical transplantation. The advantage of high-current perfusion in situ is shown, it allows the number of donor kidneys which are unfit for transplantation to be reduced to minimum. The method of in situ perfusion of organs in multiorganic collection ensures the most adequate antiischemic protection of all organs removed for transplantation, particularly in donors after circulatory arrest. PMID- 2214587 TI - [Use of perfluorocarbon emulsion in kidney transplantation]. AB - Intravenous infusion of perfluorocarbon emulsion (PFCE) during autotransplantation of kidneys which had been stored for 24 hours led to a rapid normalization of intraorganic hemodynamics in dogs, and restoration of ionic homeostasis, energy potential, and functional activity of the transplants. It was shown that the protective effect of PFCE is associated with inhibition of free radical lipid peroxidation, and the establishment of a stable protein-lipid conformation of the membrane structures of the cells of ischemic organs. It was established that the use of PFCE in the stage of stored kidney transplantation may be an effective method for the prevention of reperfusion damage to the transplant. PMID- 2214588 TI - [BCG-induced inflammation during childhood and in pregnancy. Additionally a contribution to BCG-induced necrotising cerebral arteritis]. AB - In the third year of life of a girl vaccinated neonatally against tuberculosis an abscess of the associated lymph nodes appeared which contained acid-fast bacilli. After extirpation of the lymph nodes weeks later an intestinal BCG-dissemination was observed which seemed to be cured under a brief tuberculostatic therapy. At the age of 22 years a left sided hemiplegia due to aneurysms and thrombosis of 2 cerebral arteries was seen. At autopsy in the adventitia of the arteria basilaris macrophages were discovered which showed intracellular acid-fast bacilli. A paralysis of the oculomotor nerve appearing later was also caused by this brain lesion. Towards the end of a pregnancy a serious BCG-dissemination in the intestines relapsed. A healthy premature child was born. Massive tuberculostatic therapy was inefficient. The woman died in her 27th year of life. A defective function of the macrophages is suggested for the immunological abnormality. PMID- 2214589 TI - [BCG-vaccination and its complications. How great are the benefits of vaccination today?]. AB - This paper intends to present an overview concerning the risks and benefits of BCG-immunisation basing on a research of the actual literature. The historical controversy is well known, but regarding the epidemiological situation with respect to morbidity and mortality of tuberculosis in Middle and Western Europe by now it seems to be necessary again to reflect on vaccination recommendations. While complications after vaccination may be serious or even life-threatening, immunization with BCG seems to have a beneficial effect on the incidence of infantile leukemia. Nevertheless, this effect is discussed controversially on recent research. In addition there should be drawn special attention to the problem of life-vaccines, in particular of BCG under the view of the increasing number of children with acquired immunodeficiencies. PMID- 2214590 TI - Protein supplementation of human milk for the nutrition of VLBW-infants: human milk protein vs. meat protein hydrolysate. AB - In 25 very low birth weight infants appropriate for gestational age the influences of different human milk (HM) preparations on weight gain, gross indices of nitrogen metabolism and energy balance were studied during the second month of postnatal life. HM was fortified either by HM-protein (HMP) or by an enzymatic meat protein hydrolysate (PH) to protein concentrations between 1.5 and 1.7 g/100 ml. The caloric densities of both HM preparations were similar between 62 and 68 kcal/100 ml. There were no differences in weight gain (MM + HMP: 18.6 +/- 3.4 g/kg/day; HM + PH: 16.5 +/- 4.1 g/kg/day), nitrogen retention (HM + HMP: 31.5 +/- 3.1 mmol/kg/day; HM + PH: 30.0 +/- 3.2 mmol/kg/day), and the preprandial estimated essential amino acid profiles between the both feeding groups. In contrast the serum concentrations of alpha-amino-nitrogen 60 minutes postprandially were elevated in the infants fed HM + PH in comparison to the infants fed HM + HMP. This high postprandial amino acid concentrations in serum in the group fed HM + PH were accompanied by increased bile acids concentrations in serum, higher renal amino acid excretion and increased fecal fat losses. The results suggest that due to the more rapid intestinal absorption of amino acids from PH than from HMP the concentrations of amino acids increase postprandially which results in a detectable increase of the newborn cholestasis in these infants. Nevertheless, the scale of these metabolic responses to feeding protein hydrolysates is small and without detectable influences on nitrogen retention or weight gain. PMID- 2214591 TI - [Indications for proton spin tomography in central nervous system diseases in childhood. A 4-year experience report on 164 cases]. AB - 1. Magnetic Resonance Tomography (MRT) is the method of choice for precise, comprehensive and reproducible imaging of congenital malformations and space occupying lesions. 2. MRT indicates inflammatory processes of the CNS earlier than CT by which extension and localization are visualized more precisely. MRT gains particular importance for follow-up studies because there is no radiation burden. In cases of disseminated inflammatory lesions or concerning early diagnosis of Herpes-encephalitis an exact and rapid diagnosis is possible. 3. In patients suffering from convulsions with or without focal lesions in EEG MRT instead of CT should be applied as MRT allows three-dimensional imaging not influenced by bone artifacts. 4. CT is superior to MRT if small calcifications or acute hemorrhage are looked for. MRT enables us to differentiate several stages of bleeding. 5. In patients with cerebral AV-malformations angiography can be replaced by MRT. However, angiography is indispensable for small aneurysms and AV malformations in the spinal canal. 6. Due to high soft tissue contrast MRT is the imaging modality of choice in patients with metabolic and degenerative diseases and disturbances of brain maturation. 7. In infants sonography should be done first and supplemented by MRT and/or CT. PMID- 2214592 TI - [Psychosomatic, sedative and hemodynamic reactions following preoperative administration of midazolam in children]. AB - Since children's intellectual perception is limited, the preoperative visit by an anesthesiologist alone can rarely help to free the small patients from fear and restlessness prior to elective surgery. In order to relieve anxiety which should be the primary goal of premedication in any patient - children need anxiolytic premedication agents. Drugs for premedication administered by intramuscular or rectal route in children often cause pain, fear and discomfort. The present study was performed in order to investigate oral given midazolam in the premedication of children with special regard to the practical suitability of this method. 100 children, 0.5 to 10 years of age (group A: 0.5-4 years, group B: 5-10 years) undergoing elective urological surgery received 0.4 mg/kg midazolam orally about 20 minutes prior to the arrival in the operation unit. After insertion of a venous cannula into a forearm vein anesthesia was induced with thiopental and maintained by inhalation with Isoflurane, nitrous oxide and oxygen (fi O2:0.3). Degree of sedation, state of mind and behaviour (for 100 children) as well as blood pressure and heart rate (separately for group A and B) were registered preoperatively at defined, comparable and representative circumstances. Side effects prior and during induction phase of anesthesia were documented. The personal data are representative for a normal population of children with typical urological diseases. Oral administered midazolam had only a mild or non sedative effect in 76-84% of the children 70-84% of the small patients showed an indifferent or euphoric state of mind and 67-88% behaved cooperatively or passively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214593 TI - [Metabolic disorders of branched-chain amino acids: most common forms of organic aciduria in the neonatal period]. AB - Defects in the branched chain amino acid metabolism are the most common forms of organic aciduria. Two thirds of the cases manifest themselves during the neonatal period, most of them with an acute onset. Prompt diagnosis of organic acidurias is a task of the pediatrician and the neonatologist and depends on their early identification of children with suspect clinical symptoms. Between 1984 and 1987 9 patients presented with an organic aciduria at the Pediatric Department of the University of Innsbruck, 7 of them were neonates. 4 of these 7 children had a defect in the branched chain amino acid metabolism, 3 with propionic acidemia, one with maple syrup urine disease. The remaining 3 children presented with lactic aciduria. In all our patients diagnosis was performed by combined gas chromatography and mass spectrometry of spontaneous urine samples. Diagnostic procedures and therapeutic measures applied in the acute metabolic crisis are presented. Continuous arteriovenous hemofiltration has been found to be an efficient method for eliminating toxic metabolites in intractable metabolic acidosis. PMID- 2214594 TI - [The effect of methotrexate pharmacokinetics and of leucovorin rescue on the prognosis of osteosarcoma]. AB - A total of 129 high-dosage methotrexate therapies performed in 19 patients with osteosarcoma were retrospectively analyzed. Serum methotrexate peak concentrations were found to vary widely, both inter-individually as well as in the same patient. The measured MTX peak concentrations correlated closely with pharmacokinetic data such as area under the curve and total body clearance. No correlations were found between the serum MTX correlations and different times after methotrexate administration. Increase in leucovorin rescue or low MTX peak concentrations were associated with poor prognosis. High-dosage methotrexate therapies with leucovorin rescue need to be further optimized in accordance with biochemical knowledge of the mode of action and the individual pharmacokinetic data of methotrexate. Such optimization may be expected to improve the prognosis for osteosarcoma. Serum methotrexate concentrations should be determined not only 24, 48, and 72 hours after methotrexate administration, in order to avoid elevated toxicity of the therapy, but also at the start of methotrexate infusion, in order to influence MTX peak concentrations at an early stage if necessary. Measurement of L-leucovorin in serum will be necessary, to enable a restrictive leucovorin rescue to be performed safely. PMID- 2214595 TI - [Partial trisomy 10p in combination with partial monosomy 20p--a syndrome with muscular hypotonia, psychomotor retardation, dwarfism and craniofacial dysmorphia]. AB - The clinical syndrome resulting from deletion of 20p in combination with duplication of 10p, seen in two male members of the same family, is reported for the first time. The sister of one and the mother of the other patient are asymptomatic carriers of a balanced translocation. The two patients have multiple stigmata including dwarfism and pronounced psychomotoric retardation. The syndrome corresponds largely to an addition of the symptoms seen in cases with deletion of 20p and duplication of 10p reported hitherto. PMID- 2214596 TI - [Primary hyperlipoproteinemia Type I in the neonatal period]. AB - Newborn infants with inborn errors of lipid metabolism are relatively rare. There are only a few reports of hyperlipoproteinemia in infancy. In a six-day-old "healthy" newborn infant with a weight of 2960 gm a milky blood serum was found. Diagnosis of primary hyperlipoproteinemia type I was established by exclusion of other diseases and by analysis of blood lipids. Lack of lipoprotein lipase activity in postheparin plasma confirmed the diagnosis. The parents of the patient were normolipemic but showed reduced lipoprotein lipase activity. Thus, they were recognized as heterozygotes. A low fat (6-19 gm fat/d, 2-3 gm fat/kg bodyweight/d) diet with a high proportion of medium-chain triglycerides (78% MCT) lowered the initially extremely high serum triglyceride level (3674 mg/dl) significantly (214-711 mg/dl). Until the age of 7 months body weight and length followed the 10. percentile, head circumference followed the 50. percentile. Unexpectedly the patient died of pulmonary infection at the age of 8 months. PMID- 2214597 TI - [Dentato-rubro-pallido-luysium atrophy in an infant]. AB - After an uneventful pregnancy and labour one hour post partum a tonic-clonic seizure occurred in a female infant. In the following time a muscular hypertonicity developed and the statomotor development ceased. No clue for a neurometabolic disease was found and the child died of an aspiration pneumonia at 5 months of age. Neuropathological examination disclosed a Dentato-Rubro-Pallido Luysium-Atrophy (DRPLA). Apart from two healthy siblings an older sister had died six months old after an almost identical clinical course. No autopsy was done in this first case. DRPLA is a rare systemic degeneration and begins to our knowledge always in adolescence or adult age. The nosological classification of this unusual case is discussed and the literature is reviewed. PMID- 2214598 TI - [Fatal course of juvenile chronic arthritis]. AB - Case report of a young man suffering from seropositive juvenile arthritis who succumbed to the consequences of cerebral vasculitis. Postmortem generalised arteritis was found affecting mainly brain and kidneys. There were no laboratory signs of an inflammatory process during the months before his death nor hypergammaglobinaemia or decrease of complement. The generalised arteritis manifested itself solely as mononeuritis multiplex with eosinophilia. Thus even with discrete signs such as these severe vasculitis ought to be considered for appropriate treatment to be instituted. PMID- 2214599 TI - [Spectral analysis of the ECG for detecting late potentials as risk factors of life-threatening cardiac arrhythmias]. AB - Late potentials in the terminal phase of the QRS and early S-T segment are looked upon as a risk marker in patients prone to sustained ventricular tachycardia after myocardial infarction. Since the amplitude of late potentials at the body surface is very low (1-5 microV), most studies use signal averaging of the ECG to increase the signal-to-noise ratio. Two different approaches are generally used to analyze the signal-averaged ECG. In the time domain, the individual channels are combined into a vector magnitude and high-pass filtered in a bidirectional mode. Late potentials are suspected if the filtered QRS duration is greater than 120 ms and/or the amplitude in the terminal 40 ms of the QRS complex is less than or equal to 25 microV. The limitations of this method are that the definition of abnormality differs from one study group to another, highpass filters may introduce artificial signals, patients with bundle branch block in general have to be excluded, and the definitions depend upon the noise level. More recently, spectral analysis of the ECG with Fast Fourier Transform (FFT) has been performed. Late potentials are characterized by a higher frequency content in the otherwise low-frequent S-T wave. We analyzed 25 overlapping segments of the terminal QRS and early S-T wave time shifted in steps of 2 ms with FFT (spectro temporal mapping). This method was shown to overcome some of the limitations of conventional time domain analysis: no highpass filters have to be applied, noise interference can be detected by a characteristic spectral pattern, and patients with bundle branch block need not be excluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214600 TI - [Behavior of the renal functional reserve in type I diabetic patients: effect of ACE-inhibition]. AB - Renal functional reserve capacity was evaluated in 19 normotensive type I diabetics without microalbuminuria. All patients had normal basal renal function as assessed by 24-hour creatinine clearances higher than 120 ml/min. PAH, inulin, and creatinine clearances were carried out every hour before, during, and after infusion of an amino acid (AA) solution. The same experiment was repeated after ACE inhibition with captopril (25 mg). Two groups of patients were found: Group A (responders) showed a significant rise in GFR after AA infusion (inulin clearances from 117 +/- 8 to 138 +/- 10 ml/min) (p less than 0.05), whereas in Group B (non-responders) no significant change in GFR was observed. Groups were comparable in age, duration of diabetes, metabolic control, and mean arterial blood pressure. Group B, however, had a significantly higher basal inulin clearance (167 +/- 17 ml/min) than Group A (117 +/- 8 ml/min). In Group A ACE inhibition completely blocked the AA-induced rise in GFR, while basal GFR in Group B was significantly reduced (167 +/- 17 to 148 +/- 8 ml/min) after captopril administration. In both groups renal plasma flow was enhanced by ACE inhibition. A rise in glucagon was observed in all patients during AA infusion. It is concluded that type I diabetics with normal basal renal function already have reduced (Group A) renal functional reserve capacity, which is completely abolished (Group B) when concomitant hyperfiltration occurs. ACE inhibition reduces hyperfiltration and is capable of blocking the AA-induced rise in GFR in these patients. PMID- 2214601 TI - [24-hour blood pressure measurement in normal pregnancy in hypertensive pregnant patients]. AB - Noninvasive 24-hour ambulatory blood pressure monitoring was performed in 17 normotensive and 19 preeclamptic pregnant women. The normotensive women showed a significant nightly decline in their systolic and diastolic blood pressure. In contrast, the preeclamptic women demonstrated either an attenuated circadian rhythm or no circadian rhythm at all. This result was even more pronounced in patients with severe hypertension, some of whom had a nocturnal increase in blood pressure in spite of being treated with antihypertensive drugs in an evening dose. The lack of nocturnal blood pressure decrease was also found 24 hours post partum. In summary, these results suggest that preeclamptic women are endangered by hypertensive emergencies mostly during the night. Therefore blood pressure controls should be extended into the night, and antihypertensive drugs should also be given in a sufficient evening dose. PMID- 2214602 TI - [Plasma endothelin in normal probands and patients with nephrologic-rheumatologic and cardiovascular diseases]. AB - Plasma concentrations of the recently isolated potent vasoconstrictory peptide endothelin were measured in 382 patients. The investigations were performed by means of a sensitive radioimmunoassay specific for Endothelin-1, 2. The results from 110 healthy volunteers displayed a normal range of 44.67 +/- 3.51 pg/ml. Significantly raised levels were found in 33 patients with chronic end-stage renal failure both before and after hemodialysis. In contrast, 35 patients with compensated renal insufficiency did not differ from the normals. Sixty-five patients after kidney transplantation revealed significantly elevated levels, as did 27 patients with acute myocardial infarction, 8 after coronary bypass surgery, and 5 with liver cirrhosis. The mean values of 27 patients with untreated hypertension, 22 with secondary hypertension, of various causes and 16 with coronary artery disease were comparable to the normal population. The values were significantly decreased in 9 pregnant women with hypertension and proteinuria. A marked decline was found in 5 patients with systemic lupus erythematodes, while 20 patients with rheumatoid arthritis demonstrated only a slight decrease. The pathophysiological role of endothelin as a local or circulating hormone in regulating systemic blood pressure or release of other hormones remains to be determined. PMID- 2214603 TI - Cystic neoplasms of the pancreas: a clinical and radiological study of eight cases. AB - Four patients with benign serous cystadenoma, one with mucinous cystadenoma, and three with mucinous cystadenocarcinoma treated in the university hospital of Gottingen between 1985 and 1988 were investigated. The main initial symptoms of these cystic tumors were abdominal pain (7/8), weight loss (3/8), maldigestion (3/8), and palpable abdominal mass (3/8), while laboratory investigations revealed nonspecific alterations (elevated ESR, mild hypochromic anemia). CA 19-9 was elevated in two patients, one of whom had cystadenocarcinoma; CEA also was elevated in this patient only. In all cases size, localization, and cystic character of the tumors were shown clearly by sonography and computed tomography; fine needle biopsy helped to distinguish between serous and mucinous cystadenoma in four of six cases. Because of their malignant potential, total extirpation of mucinous cystic tumors is the treatment of choice, while serous cystadenomas are benign and therefore may be treated conservatively in uncomplicated cases or high risk patients. PMID- 2214605 TI - Duplex sonography in the diagnosis of renovascular hypertension. AB - Duplex sonography (DS) has become a well established method for diagnosing peripheral vascular diseases. Technical developments (higher resolution of transducer and deeper penetration) have made also abdominal and retroperitoneal vessels, including renal arteries, accessible for duplex sonography. This method provides the opportunity to recognize renal artery stenoses causing renovascular hypertension without invasive procedures. We therefore examined 86 hypertensive patients with a high likelihood of renovascular hypertension. Due to technical problems (bowel gas, adipositas) we excluded 7 patients. 79 patients (17-79 years) were included in our study. Flow patterns of several renal vascular areas were evaluated while the renal artery was demonstrated on a B-scan. A spectrum analysis included the evaluation of the frequency pattern (widening of the frequency band and loss of a frequency free window below the systolic rise?), the sloping of the diastolic shoulder, and the calculation of different parameters like acceleration index, deceleration index, resistance index, acceleration time, and systolic peak velocity. The accuracy of DS in diagnosing renal artery stenoses was compared with arterial digital subtraction angiography (DSA). Renal artery stenoses was diagnosed in 21 out of 158 renal arteries (13%). Except for the systolic peak velocity no significant correlations could be found of any of the indices from spectrum analysis with hemodynamically significant stenoses (greater than 50%). However, the following 3 criteria proved to be valuable signs of a hemodynamically significant stenoses: 1) Maximal systolic acceleration greater than 3 m/s, 2) Steep sloping diastolic shoulder, and 3) Turbulence of all frequency ranges without a frequency free window below the systolic rise. Compared with DSA the sensitivity of DS was 84.0%, the specificity was 98.5%, and the predictive value 91% in significant stenoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214604 TI - Effects of long-term treatment with simvastatin on plasma lipids and lipoproteins in patients with primary hypercholesterolemia. AB - We investigated long-term hypolipidemic effects and clinical safety of simvastatin, a new competitive inhibitor of 3-hydroxy-methylglutaryl coenzyme A reductase in 24 patients with familial and non-familial hypercholesterolemia. Patients received up to 40 mg simvastatin for a period of 30 months. Significant decreases were noted in plasma cholesterol (30%), plasma triglycerides (25%), very low density lipoprotein-cholesterol (26%), and low density lipoprotein cholesterol (40%), whereas an increase in plasma high density lipoprotein cholesterol (11%) was observed. Furthermore, the percentage decrease in plasma low density lipoprotein cholesterol was independent of individual baseline concentrations. Simvastatin did not alter the composition of low density lipoproteins or high density lipoproteins. The percentage decrease in total plasma and low density lipoprotein-cholesterol was independent of apoprotein E isoforms and low density lipoprotein-receptor activity as assayed in cultured fibroblasts. The drug therapy was well tolerated and clinical examinations revealed no adverse effects. Clinical chemistry indices and hematological, as well as endocrinological parameters remained within normal limits and ranges. PMID- 2214606 TI - [Studies on cultured rat mesangial cells using cyclosporin A and magnesium--is magnesium nephroprotective in cyclosporin A therapy?]. AB - One serious side effect of Cyclosporine A therapy is its acute nephrotoxicity characterized by a marked decrease in the glomerular filtration rate. A main determinant of the glomerular filtration rate is the ultrafiltration coefficient which is thought to be regulated by the contractile state of the cells of the mesangium. Cyclosporine A enhances contractions of mesangial cells elicited with angiotensin II. By way of lowered ultrafiltration coefficient this effect of Cyclosporine A may be partly responsible for its acute nephrotoxicity. Hypomagnesaemia is often associated with Cyclosporine A therapy. Profound tubular magnesium wasting by Cyclosporine A has been claimed its cause. We have investigated the effect of low and high magnesium concentration on the contractility of mesangial cells pretreated with Cyclosporine A. Without magnesium 80% of the cells contracted upon addition of angiotensin II. A marked decrease in the contractility was seen when the magnesium concentration was elevated to 2 mmol/l (34%). From these observations we conclude that magnesium serum levels even in the high normal range might be protective against the decrease of the glomerular filtration rate seen with CsA therapy. PMID- 2214608 TI - Influence of splenectomy on platelet morphometry and function. AB - Functional and morphometric platelet abnormalities may be influenced by splenectomy and thus contribute to postoperative thrombohaemorrhagic complications, especially in patients with splenomegaly and/or platelet defects. We investigated platelet function, platelet secretion, and platelet morphometry before and one week after splenectomy in seven patients with normal platelet production and normal spleen size (Hodgkin's disease) and five patients with splenomegaly and platelet abnormalities (4 with myeloproliferative disorders and 1 with chronic myelomonocytic leukemia). Severe postoperative thrombohaemorrhagic complications occurred only in patients with myeloproliferative disorders, although platelet count and mean platelet volume increased in almost all patients after splenectomy. Four patients with myeloproliferative disorders had impaired platelet aggregation before splenectomy that improved in only one patient after surgery. Platelet buoyant density in this patient group was decreased before splenectomy and normalised thereafter. Concomitantly, intraplatelet concentrations of alpha-granular proteins increased. Before splenectomy, there was a positive correlation between platelet density and platelet volume in patients with Hodgkin's disease (r = 0.59, p less than 0.001), but not in patients with myeloproliferative disorders. There was no correlation between platelet density and platelet volume after splenectomy in either patient group. In conclusion, morphometric platelet abnormalities were found in all patients after splenectomy. In patients with myeloproliferative/myelodysplastic disorders, decreased platelet buoyant density normalised and intraplatelet concentrations of alpha-granule proteins were elevated after splenectomy. However, platelet function defects in this patient group were not corrected and may have been a major cause of thrombohaemorrhagic complications in the postoperative period. PMID- 2214607 TI - Tumor necrosis factor: an update on basic research and clinical applications. AB - Tumor necrosis factor is one of the recently cloned cytokines with pleiotropic effects on normal and malignant cells. Our knowledge about the scope of cells producing or responding to this cytokine has enormously expanded. In critically ill patients with acute hepatic failure, acute graft-versus-host disease, or septic shock, circulating tumor necrosis factor can be measured and useful prognostic correlations do exist. Despite promising in vitro results, early clinical trials with tumor necrosis factor for the treatment of cancer have failed thus far to reveal major antineoplastic activity in cancer patients. However, more clinical trials are necessary, since different routes of administration and combinations with other cytokines may lead to favorable results. PMID- 2214609 TI - Highly variable clinical course in severe alpha 1-antitrypsin deficiency--use of polymerase chain reaction for the detection of rare deficiency alleles. AB - Among 20 individuals with severe alpha 1-antitrypsin (alpha 1AT) deficiency we observed extremely variable clinical phenotypes ranging from rapidly progressive lung disease fatal at the age of 42 years to an asymptomatic individual with normal lung function at the age of 50 years. Eighteen subjects, including the asymptomatic one, carried the deficient Pi ZZ phenotype as determined by isoelectric focusing (IEF). Their mean alpha 1AT serum level was 36.7 +/- 7.7 mg/dl. DNA restriction analysis showed that all of them had the classical Pi Z allele-associated DNA haplotype, thus confirming the IEF data. Obviously not all Pi ZZ individuals will have clinical sequelae caused by this genotype. The important differences in clinical course observed could not be explained by smoking habits alone. Probably additional factors are pertinent to the pathogenesis of the lung disease associated with alpha 1AT deficiency (defects in other genes, environmental influences other than smoking). In two patients with very low alpha 1AT serum levels definitive phenotyping by IEF was not possible. Therefore we investigated the molecular basis of their deficiency using polymerase chain reaction (PCR) amplification of the coding exons of their alpha 1AT genes and direct sequencing of the amplification products. Sequence data analysis showed that one of these patients, who had initially been phenotyped as Pi ZZ by IEF, had in fact the genotype Pi QObellinghamZ, thus explaining her low alpha 1AT serum level of 20 mg/dl. The other patient (alpha 1AT serum level 3.7 mg/dl) exhibited the rare genotype Pi MheerlenQOgranite falls. Despite his nearly complete alpha 1AT deficiency, he suffered from only moderately severe pulmonary disease at the age of 42 years. PMID- 2214610 TI - [HIV-1 antigenemia and T-cell activation in HIV-1 infected patients]. AB - In order to study a supposed association between T-cell activation in vivo and HIV-1-antigenemia in HIV-1-infected patients, the detection of p24-antigen in sera was correlated to serum levels of beta-2-microglobulin and C1q-binding immune complexes. Anti-p24-antibodies and the urinary excretion of neopterin were also analysed. In 24 of 80 patients (30%) p24-antigen could be detected, and in 15 of 59 (25.4%) there was a loss of anti-p24-antibodies. Tests revealed elevated serum levels of beta-2-microglobulin in 58 of 80 patients (72.5%), elevated levels of C1q-binding immune complexes in 15 of 66 (22.7%), and increased excretion of neopterin in 52 of 60 (86.7%). Detection of p24-antigen, loss of anti-p24-antibodies, serum levels of beta-2-microglobulin, and urinary excretion of neopterin were significantly correlated to advanced stages of HIV-1 infection. Patients with p24-antigen in the serum showed significantly more frequently elevated serum levels of beta-2-microglobulin and no significant association with increased urinary excretion of neopterin. Because of the high proportion of patients with elevated serum levels of beta-2-microglobulin and increased excretion of urinary neopterin in the absence of detectable p24-antigen in serum, we could not correlate HIV-1-antigenemia to T-cell activation in vivo. PMID- 2214611 TI - Urinary excretion of N-acetyl-beta-D-glucosaminidase in patients after cyclosporin-treated corneal grafting. AB - Allograft rejection occurs in up to 70% of high-risk keratoplasty patients. For this reason short-term Cyclosporin treatment was administered for three months to prevent graft loss. Of 23 renal healthy patients, 19 enjoyed long-term graft acceptance. We evaluated in these patients N-acetyl-beta-D-glucosaminidase (NAG) excretion as a marker of renal tubular damage. All patients, except one, showed urinary NAG excretion to be within the normal range. From this we conclude that no renal tubular damage occurs after short-term Cyclosporin treatment. PMID- 2214612 TI - Ciclosporin-propafenone interaction. PMID- 2214613 TI - Improvement of the exercise capacity of a patient with primary orthostatic hypotension (primary sympathetic insufficiency) by programmed subcutaneous noradrenaline administration via microdosing pump. PMID- 2214614 TI - Acute uric acid nephropathy in two gouty patients with moderate hyperuricemia and high urine acidity. AB - Acute uric acid nephropathy has been described almost uniformly in patients with massive uric acid overload (malignancies with rapid cell destruction, epileptic seizures). Severe hyperuricosuria and intratubular uric acid precipitation result. Here we present two patients with gout, normal uric acid production, and moderate hyperuricemia, both of whom developed acute uric acid nephropathy. Because of pronounced urine acidity (pH values of 4.6 and 5.0 in morning fasting urines), supersaturation with respect to undissociated uric acid exceeded solubility (0.54 mmol/l), despite basal urate secretions of less than 2.2 mmol/24 hours. Additional predisposing factors, such as uricosuric treatment, heavy beer drinking, over-consumption of purine-rich foods, and hot environment, were superimposed in both cases. PMID- 2214615 TI - Severe granulomatous giant cell myocarditis in Wegener's granulomatosis. AB - A 28-year-old male patient suffering from Wegener's granulomatosis died suddenly with signs of cardiac failure after clinical symptoms had basically subsided under chemotherapy. Autopsy revealed pulmonary granulomata, necrotizing vasculitis of the lungs and kidneys, focal and segmental necrotizing glomerulonephritis, and diffuse granulomatous and necrotizing giant cell myocarditis. Histological confirmation of inflammation of the heart in Wegener's disease has rarely been reported. Although cardiac involvement in Wegener's granulomatosis sometimes is suspected, it is usually thought to have no major impact on the course of the disease. By its dramatic clinical and morphologic presentation this case illustrates that the heart, in addition to the lungs and kidneys, may determine the outcome of the idiopathic granulomatous vasculitis of Wegener. PMID- 2214616 TI - [Campylobacter pylori in patients with peptic ulcer and chronic gastritis: immunologic response]. PMID- 2214617 TI - [Colonoscopy in the diagnosis and follow-up of colonic polyps]. AB - Out of 5000 patients examined endoscopically colon polyps were detected in 64%. The polyps were characterized by: higher incidence in 70-79-year-olds, high percentage of tubular adenomas (79%), large sizes of polyps with complex structure and their prevalence in the left colon, signs of malignancy in 0.64% of the removed polyps. The chance to develop cancer from tubular adenoma was 0.28%, tubular-villous, 1.4%, villous 3%. Recurrent polyps following polypectomy arose in 65% of cases. Tumor relapses emerging mainly within the first postoperative year occurred in 14% of cases. In 4 patients with cancer its onset was registered at the site of the removed large adenomas of complex histological structure. Colonoscopy proved an adequate method of diagnosis and follow-up of colon polyps. Endoscopic polypectomy can be considered as a measure to prevent colon cancer. PMID- 2214618 TI - [Use of xenobiosorption in the treatment of a severe form of brucellosis]. AB - Brucellosis sepsis was treated by xenosorption involving the porcine spleen. Compared to standard therapy ineffective in protracted sepsis, the biosorption provided good results leading to a rapid arrest of the infectious process and eventual elimination of the organisms. As the data on related experience are not available in the literature, the above technique of brucellosis treatment is believed fresh. PMID- 2214619 TI - [Immunoreactive trypsin in the blood serum of patients with endogenous hypercorticism]. AB - Radioimmunoassay (RIA) was used to measure the response of serum trypsin to intravenous secretin and pancreozymin in 16 subjects with adrenocortical hyperfunction (group I) versus 6 subjects with hypercorticism (group II). In group I the enzyme reaction to the peptides was active and long-term. A similar rise in trypsin level occurred equally in patients free of chronic pancreatitis often present in Itsenko++ -Cushing syndrome. In group II patients RIA trypsin values comply with normal levels. The data obtained suggest an affected pancreatic status in adrenal hyperfunction both in the presence and absence of chronic pancreatitis which minimizes the informative value of the test in identification of chronic pancreatitis in endogenic hypercorticism. PMID- 2214620 TI - [The role of glucocorticoid receptors and HLA antigens in the pathogenesis of Cushing's syndrome]. AB - Lymphocytic levels of glucocorticoid receptors were evaluated in 114 patients suffering from Icenko-Cushing's syndrome. Incidence of HLA antigens was determined in 94 of them. A significant rise of A10 and B27 antigen incidence compared to that in normal subjects allows these antigens to be considered genetic markers of Icenko-Cushing's syndrome. The levels of glucocorticoid receptors in lymphocytes of the patients are lower than in normal subjects both in the active stage of the disease and following bilateral total adrenalectomy. The patients carrying B27 antigen had lymphocytic receptor concentrations under the levels of such in patients free of the antigen carriage. Antigen B27 seems to be a cause of lower levels of glucocorticoid receptors in blood lymphocytes. PMID- 2214621 TI - [A case of left-atrial myxoma]. PMID- 2214622 TI - [Developmental defect of the pulmonary artery in a patient with bronchial asthma]. PMID- 2214623 TI - [HLA antigens in monozygotic twins with the concordance of appendicitis and complicated duodenal ulcer]. PMID- 2214624 TI - [Pharmacological basis of thrombolytic therapy]. PMID- 2214625 TI - [Current approach to the treatment and secondary prevention of peptic ulcer in different settings]. AB - The authors believe that gastroduodenal ulcer can be treated efficiently in the outpatient setting and day hospitals. Indications are suggested to treatment under either conditions. Arguments are proposed in favor of correcting standard regimens, diet, chemotherapy, optimal terms of control endoscopy dependent on the ulcer size and depth and of preventive treatment with regard to different ulcer courses, etc. PMID- 2214626 TI - [Comparative effectiveness of the treatment od patients with hyperglycemic coma in diabetes mellitus with small and large doses of insulin]. AB - The results of the study involving 123 patients suffering from hyperglycemic diabetic coma lead to the conclusion on ineffectiveness of high-dose insulin. Treatment of hyperglycemic coma by low-dose insulin is more preferable as warranting continuous decrease of glycemia without its transformation into hypoglycemia, ++post-hypoglycemia hyperglycemia, brain edema. PMID- 2214627 TI - [Phases of recurrence of peptic ulcer]. PMID- 2214628 TI - [Various methodological aspects of patient interviewing]. AB - The paper recommends a number of rules useful in interviewing patients, draws attention to some typical mistakes made by physicians gaining clinical information from their patients. It is thought advisable to provide medical students with advanced guidelines how to manage a valid and informative interview of patients. PMID- 2214629 TI - [Principles of teaching the methods of differential diagnosis in internal medicine]. PMID- 2214630 TI - [Use of the rating system in the evaluation of professional competence of therapists and surgeons]. PMID- 2214631 TI - [Observation of the physician and talent of the writer (on the novel by A.P. Chekhov "The steppe")]. PMID- 2214632 TI - [Aleksandr Efimovich Rabukhin (on his 90th birthday)]. PMID- 2214633 TI - [Pathogenesis of diabetic nephroangiopathies]. PMID- 2214634 TI - [Cardiomyopathies: nosological entities, classification and the pathomorphological aspect of diagnosis]. PMID- 2214635 TI - [Actual problems of clinical hemostasis]. PMID- 2214636 TI - [Sneddon syndrome: cardiac pathology and anti-phospholipid antibodies]. AB - Besides cerebrovascular pathology and livedo, cardiac affections are introduced in clinical manifestations of Sneddon's syndrome. They involve coronary heart disease (up to development of MI), murmur (usually mitral), occasional cardiac arrhythmia. Patients with coronary disease and cardiac murmur show antibodies to cardiolipin significantly more frequently. The role of antibodies to cardiolipin in the genesis of cardiac alterations in Sneddon's syndrome is open to discussion. PMID- 2214637 TI - [Secondary amyloidosis in elderly patients with rheumatoid arthritis]. AB - Examination of rheumatoid arthritis (RA) patients (52 males and 35 females) revealed secondary amyloidosis (SA) in 44.2% and 48.6% of patients, respectively. The disease was confirmed by amyloid deposits in biopsy specimens of gingival mucosa. As far as age-specific SA incidence is concerned, SA was more prevalent in elderly age-groups: 29.7% and 80% in males under and over 50, respectively; 15.4% and 68.2% in relevant women. The disease history in old patients was not long: 4.6 +/- 1.0 yr and 3.3 +/- 0.7 yr for males and females, respectively. Not a single case of amyloid deposit occurred in patients with systemic lupus erythematosus at the age over 60. The contribution of sex hormones and other factors to SA onset in RA is under discussion. An old age of RA patients and associated infection, especially urogenic, can predispose to SA development. PMID- 2214638 TI - [Hemostatic disorders in patients with Schoenlein-Henoch syndrome]. AB - Several indices of coagulation and fibrinolysis were studied in 54 patients suffering from Schonlein-Henoch disease. A significant prolongation of platelet aggregation was found in parallel with a decrease of AT III and plasminogen and an increase of the fibrin monomer complexes. Consequent to heparin treatment controlled by measurements of residual thrombin activity, the indices showed a trend towards normalization. The dynamic monitoring of the above indices can be used for an overall assessment of the heparin treatment. PMID- 2214639 TI - [Immunological and rheological parallels in patients with autoimmune thrombocytopenic purpura treated with antilymphocyte globulin]. AB - When assessed in 20 patients with autoimmune thrombocytopenic purpura (ATP), immunologic and rheologic characteristics demonstrated shifts in the presence of hemorrhagic syndrome. These correlated shifts emerged upon 4-5 infusions of antilymphocytic globulin (ALG) and could contribute to the onset of hemorrhagic syndrome observed in 25% of the patients. To arrest or prevent unwanted hemorheologic and immunologic effects, 5 ATP patients received pathogenetic treatment promoting removal from the circulating blood of antithrombocytic antibodies, cell destruction products, circulating immune complexes. Plasmapheresis included as such treatment in multimodality ATP treatment led to correction of rheologic and clinico-hematologic++ alterations and eventual compensation of the disease. Plasmapheresis is proposed as monotherapy and as an adjuvant to ALG treatment of ATP. PMID- 2214640 TI - [Functional and morphological characteristics of a hematuric form of chronic glomerulonephritis]. AB - Clinical evidence has been analyzed for 325 patients with chronic glomerulonephritis confirmed histologically. It was established that chronic glomerulonephritis (CG) associated with hematuria exhibits some specific characteristics: great ability for maximal osmotic concentration and partial ability for ammonium excretion in membranoproliferative CG without sclerotic lesions, maximal occurrence in membranoproliferative form of the disease; fibroplastic transformation of the glomeruli is a rare finding. CG with hematuria is worth mentioning in CG diagnosis. PMID- 2214641 TI - [Clinical, immunological and morphological evaluation of nephrotic syndrome]. AB - The results are available of combined examination of the kidneys in 84 patients with manifest nephrotic syndrome varying in etiology: 57 had glomerulonephritis, 18 amyloidosis, 9 diabetic nephropathy. The study covered lipid metabolism, immunological status, lifetime morphological investigation of the kidneys. The latter procedure proved advantageous over biochemical and immunological studies in deciding upon nosological diagnosis of nephrotic syndrome and its prognosis. Destruction of podocytic miner processes revealed in all the syndrome cases can serve a uniform morphological substrate underlying massive proteinuria. PMID- 2214642 TI - [Effect of therapeutic plasmapheresis on the system of hemostasis in patients with chronic glomerulonephritis]. AB - Coagulative and thrombocytic hemostasis as well as the fibrinolytic system were studied in 20 patients with chronic glomerulonephritis on plasmapheresis (PA). It is shown that PA promotes activation of platelet aggregation which can be related to their contact activation. Coagulation enhances, antithrombic potential reduces, fibrinogen is mechanically removed as well as fibrin-monomer soluble complexes, fibrin degradation products. In view of the importance of the fibrinolytic system in chronic glomerulonephritis, measures should be taken to correct the disturbances detected. PMID- 2214643 TI - [Immunoglobulin and lysozyme levels in bronchoalveolar lavage fluid from patients with acute pneumonia in acute leukemia and bronchogenic carcinoma of the lung]. AB - The study of immunoglobulins and lysozyme in acute pneumonia patients suffering from acute leukemia and bronchogenic cancer of the lungs elicited impairment of local specific and nonspecific body defences. This fact should be taken into consideration when planning immunotherapy in combined treatment of relevant patients. PMID- 2214644 TI - [Bronchoconstrictive and bronchodilating effects of acetylsalicylic acid in patients with bronchial asthma]. AB - An aspirin test has been performed in 100 asthma patients. The response of the bronchi appeared contradictory: aspirin asthma on the one hand, and bronchodilatation on the other occurred in 31 and 28 patients, respectively; 41 patients appeared nonresponders. Maximum effect of the drug was noted in the small bronchi. Desensitization to aspirin and hemosorption reduced asthma patients sensitivity to nonsteroid antiinflammatory drugs. PMID- 2214645 TI - [Pathogenetic variants of the obstructive syndrome in patients with bronchial asthma]. AB - The study is made of the causes underlying a variety of obstruction syndrome presentation in bronchial asthma sufferers. Heterogenic pathogenesis of the disease is related to predominance of one of the three obstruction components: bronchospasm, inflammatory edema of the mucosa and sputum obturation of the airways as a result of defective expectoration. To quantify the components objectively, a special program of the patients' examination has been devised involving: 1) analysis of clinical symptoms, 2) pharmacological testing with selective and nonselective sympathomimetic agents and cholinolytics, 3) registration of the duration of the bronchial sputum evacuation (time of expectoration). Basing on relevant results, three variants of the obstruction are distinguished: bronchospastic, inflammatory-edematous++, obturation. The severity of bronchial obstruction progresses from the first to the third variant. Moreover, the efficacy of bronchospasmolytic drugs diminishes as shown by pharmacological tests: first of selective beta 2-agonists and cholinolytics followed by non-selective sympathomimetic agents which may be attributed to their additional alpha-stimulating action. In view of this the question of clinical significance of alpha-stimulated bronchial constriction is discussed with reference to original and literature data. PMID- 2214646 TI - [Effectiveness of depin-E in patients with chronic bronchitis]. AB - Acute course and long-term regimens of depin-E administration were evaluated clinically and pharmacologically in 50 patients with chronic obstructive bronchitis (COB) and chronic cor pulmonale (CCP). The drug has three mechanisms of action: arteriolovenodilating, bronchodilating, direct pulmonary vascular. Therapeutic effect was achieved in 80% and 60% of COB and CCP patients, respectively. No response was demonstrated for patients with severe cardiac failure. Depin-E can be recommended for prophylaxis and treatment of CCP, to arrest hypertension crises in lesser circulation, to improve pulmonary circulation, central hemodynamics, exercise tolerance. PMID- 2214647 TI - [Respiration and bronchial patency in patients with bronchial asthma during physical exercise]. PMID- 2214648 TI - [Effectiveness of endobronchial administration of granulocyte concentrate in patients with various forms of chronic bronchitis]. AB - The paper concerns the efficacy of endobronchial introduction of fresh donor leukocytic mass which was studied in 56 patients with chronic obstructive bronchitis and compromised immunity in hypoactivity of alveolar macrophages. The above treatment promoted correction of the immunity shifts, activation of alveolar macrophages and eventually better prognosis in relevant patients. PMID- 2214649 TI - [Experience with individual corticosteroid therapy of bronchial asthma in middle aged and elderly patients (controlled by monitoring of blood tyrosine level)]. AB - Blood level of tyrosine as a new clinical and laboratory indicator has been studied in bacterial asthma patients of advanced age. Tyrosine is known to affect metabolism of glucocorticoid hormones (GHs) thus reflecting GHs status of the body and permitting valid evaluation of the need in corticosteroid therapy. PMID- 2214650 TI - [Nursing care for the adolescent (II). Suicide in adolescents]. PMID- 2214651 TI - [Factors influencing one's ability to adapt to chronic illness]. PMID- 2214652 TI - [A case study on a facial palsy patient]. PMID- 2214653 TI - [The effect of various cleansing methods for total fiber optic colonoscopy]. AB - It is a fact that there are recent increasing trends of incidence of the colorectal carcinoma among other colorectal diseases. In such trend, the early detection remain to be most important by the air contrast barium enema and total fiber optic colonoscopy There are several ways to prepare the colon for barium enema and fiber optic colonoscopy which include several agents. The mechanical cleansing have been used most frequently since Brown's method was adapted to be most perfect for colon cleansing. The ideal laxatives and enema solutions were limited to adequate dose, it's effectiveness, patient's diet and bowel habit, minimal side effect, low cost and simple to perform. In order to compare the effectiveness of various cleansing solutions, six experimental methods were formed as shown; 1. normal saline enema, 2. castor oil with normal saline enema, 3. castor oil with soapsuds enema, 4. magnesium citrate with normal saline, 5. magnesium citrate with soapsuds enema and 6. ingestion of Golyetly solution. The authors have compared and determined the degree of cleanliness by an experienced endoscopist The total number of patients was 247, age distribution was 43 +/- 15 years old, and sex distribution was 133 males and 114 females. The grade I and II represented no difficulties at performing the fiber optic colonoscopy+, but grade III and IV had some difficulties, even unable to perform the fiber optic colonoscopy. The effectiveness the cleansing agents, represented with grade I and II was 95.9% (47/49) in method 6, 93.2% (54/58) in method 2, 83.3% (30/33) in method 3, 70.0% (28/40) in method 5, 66.7% (16/24) in method 1, and 45.7% (18/40) in method 4. Method 2 and 6 were the most effective in normal bowel habit patients. In constipated patients, method 6 was the most effective and all method except method 4 were effective in diarrhea patients. The degrees of less mucosal irritation by various bowel cleansing method were in the order of method 6(100%), 1(100%), 5(74%), 2(69%). In subjective symptoms and cleansing groups, abdominal distension, pain, nausea and vomiting were complained, and that's subject symptoms were in the order of method 3(88.9%), 6(79.6%), 1(75%), 5(72.5%), 2(72.4%), 4(67.5%). In conclusion, we believe that the Golytely of the mechanical cleansing solution for fiber optic colonoscopy was the most effective, but others depended on the patient's condition and bowel habit. PMID- 2214654 TI - [A study on the effect of waiting time for operations in the operating room on preoperative patients]. AB - This study was attempted to provide us with basic information on how to improve understanding with patients for operation, and to offer them better nursing and treatment. This kind of study will help scientific application to nursing practice and operating room. The data was collected by interviewing 29 patients who underwent the elective surgery under the general anesthesia at Y hospital in Seoul. The interview ran from October 15 to December 15, 1989. The research instrument was a anxiety measurement device (SAAI) originally developed by Spielberger, et al and modified by Jung-Tack Kim. 1. Hypothesis Testing Hypothesis one was that there would be a difference in state anxiety level according to a time difference in waiting for operation. This hypothesis was rejected (state anxiety level one hour before operation P greater than .05, r = .747, State anxiety level half an hour before operation P greater than .05, r = .1550, state anxiety level just before operation, P greater than .05, r = .1099). However, state anxiety level appeared to be associated with a longer waiting period, like one day before operation (P less than .05, r = .4628). Hypothesis two was that there would be a difference according to state anxiety level of patients for operation. This was rejected. (Change of blood pressure in systolic P greater than .05, r = -.1082. Change of blood pressure in diastolic P greater than .05, r = -.088, Change of pulse rate, P less than .05, r = 1.909) 2. Examining trait anxiety and state anxiety levels, the average level of trait anxiety was 42.034, and the average level of state anxiety one day before operation was 43,000. The average level of state anxiety was averaged 42.356 in a waiting room for operation. 3. Examining the state anxiety level by time period, the level one hour before was 42.379, the level half an hour before 42.276, and the level just before operation 42.414. The low level of state anxiety was due to the fact that premedication was not eliminated. 4. Age and time period like one day before operation was related to state anxiety level (F = 5.271, P less than .001) and blood pressure in waiting room for operation. That is, state anxiety level and blood pressure of patients one day before operation appeared high. Sex was related to changes of blood pressure; the blood pressure of male patients appeared higher than that of female patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2214655 TI - [Health belief model and sick role behavior of Korean chronically ill patients]. AB - This article reviewed & analyzed 33 studies of the Health Belief Model applied to korean chronic ill patients which were published from 1975 to 1990. The findings of analysis are as follows. The subjects of researchs are patients with various chronic illness including Pulmonary Tb., DM., Hemodialysis & Kidney Transplantation, Hypertension, etc. The type of research is retrospective survey in all studies. The measurement of health belief in all studies & sick role behavior in most studies have relied on self report. The analysis of the relationship between health belief and sick role behavior was done using correlation coefficient in most studies. To analyze empirical support for the relationship between health belief and sick role behavior, Significance ratio was computed. This ratio is value wherein the number of statistically significant findings with relationship in the expected direction for an HBM dimension are divided by total number of studies which reported significance levels for that dimension. Examination of this ratio across the 33 studies reveals susceptibility (30.3%), severity (34.4%), benefit (65.6%), barrier (50%). The following suggestions are based on the above findings and literature review. 1. It is necessary to develop the reliable, valid and standardized instrument for measurement of health beliefs. 2. In the further measurement of perceived susceptibility of the chronic ill patients. It is considering that the perceived susceptibility and perceived severity are measured together or the measurement of perceived susceptibility is eliminated. 3. Relationship between perceived severity and sick role behavior is suggested to be analized using ANOVA, chi 2 square instead of correlation coefficient. 4. Sick role behaviors should be measured by both self report and objective measurement. 5. Prospective, longitudinal survey should be needed. 6. Other factors influencing sick role behaviors of chronic ill patients should be investigated further. PMID- 2214656 TI - [Nursing care for the adolescent (II). Drug abuse in adolescents]. PMID- 2214657 TI - [A study on third-trimester gravidas' knowledge of infant care activity]. AB - The purpose of this study was to measure the degree of gravidas' knowledge of infant care activity, and to identify the factors influencing the difference of gravidas' knowledge. The subjects of this study consisted of 159 gravida visited 2 general hospitals, 2 OB/GY clinics and 2 midwives' clinics in J city for antenatal care. The data were collected from December 1 to 30, 1989. The instrument used for this study was true false type question which was developed by investigator through literature review. Data were analyzed by percentage, mean, t-test and ANOVA on significant difference with SPSS program. The results of this study were summarized as follow: 1) The degree of gravidas' knowledge of infant care activity was 36.75, the degree of gravidas' knowledge of physical care activity was 16.70, and the degree of gravidas' knowledge of psychosocial care activity was 20.05. 2) Among the physical care activity knowledge items, the diaper should be changed whenever it is soiled, shortly after feeding is over, bathing is bad, gently patted or stroked on the back when bubbling, 10 minutes time in bathing is appropriate, infant is crying whenever he is hungry per 3-4 hours, and room humidity controlled 60 percent, more or less were over a percentage of 80 of right answer. Among the physical care activity knowledge items, a reason for burping was the air he has swallowed will rise to the top of his stomach and be eructated, burping is advisable after the feeding, dressing of umbilical area is not necessary, the thermometer should not be boiled for disinfection, it is important that the infant grasp the whole nipple within his mouth, using alcohol sponge is bad whenever diaper is soiled, and when temperature is taken by the rectal method, infant legs should be grasped firmly were less than a percentage of 60 of right answer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2214658 TI - [Problem of automated evaluation of the functional state of the body in current aerospace and preventive medicine]. AB - The methodology of evaluating the health status of the normal man is discussed. Special attention is given to the boundary states between the norm and pathology, i.e. ++pre-nosological and premorbid states. The development of automatic systems for evaluating the functional state of the human body is described. A motor-borne automatic system "Autosan-82" is described as a ground-based analog of a space system of medical monitoring. Also, a description of present-day automatic systems "Control", "Vita", and "Rhythm" is given. They can provide health evaluation at three levels: 1) preliminary assessment and identification of subjects in different health conditions; 2) diagnosis of functional states, identification of risk factors, and potential profiles of pathology; 3) medical examinations by specialists in different medical disciplines of subjects with potential pathologies or detailed evaluation of reserve capabilities of health subjects. PMID- 2214659 TI - [Hormonal regulation of calcium metabolism after space flights of different duration]. AB - This paper presents the results of examinations of 19 cosmonauts, 12 of whom made 7-day flights and 7 took part in space flights of 150, 211 or 237 days. In plasma, parathyrin, calcitonin and gastrin concentrations were measured. A complex mosaic of hormonal regulation of bone metabolism reflects multifactorial and flexible patterns of calcium homeostasis, with individual variations included. It is probable that the specific weight of different components of the system maintaining calcium homeostasis varies depending on the exposure time and activity of related regulatory systems. PMID- 2214660 TI - [Study of the musculoskeletal system of the spine in humans after long-term space flights by the method of computerized tomography]. AB - By computer tomography, mineral density of lumbar vertebrae and their segments as well as back muscle (++ilio-costal, extensor and ++inter-spinal) density and mass were measured in four Salyut-7 crewmembers before and after extended flights (of 5 and 7 months in duration). These findings are in good agreement with the results of prolonged bed rest studies in which trabecular bone of vertebral bodies was investigated: mineral density diminished only in some (approximately 10%) of the test subjects. At the same time mineral density loss was seen in the vertebral elements where muscles were attached. Also, muscle mass was reduced. It is emphasized that the level of changes was not correlated with flight time. Further investigations in this area are discussed. PMID- 2214661 TI - [Studies of the morphology of the thyroid gland and thyroid hormone levels in the blood of rats in experiments on "Kosmos-1667" and "Kosmos-1887"]. AB - Using histological, electron microscopic, and biochemical (measurement of total thyroxine, free thyroxine and triiodothyronine in plasma) method, thyroid glands of 17 male rats of the Wistar SPF strain flown for 7 days on Cosmos-1667 and for 13 days on Cosmos-1887 were investigated. It was found that a longer exposure to space flight effects (for 13 days) led to a thyroid activity decline (significant reduction of thyrocyte size and nuclear area, accumulation of colloid drops in the cytoplasm, decrease of iodinated thyroglobulins in the colloid, etc.) together with a substantial decrease of T4 and T3 in plasma. The above structural and functional changes in the thyroid gland and hormonal status are characteristic of a moderate stress-reaction and reflect variations of the early and intermediate stages of adaptation to microgravity during 7- and 13-day space flights. PMID- 2214662 TI - [Functional activity of the pituitary-thyroid gland system during 370-day anti orthostatic hypokinesia]. AB - The concentrations of the thyrotrophic hormone (TTH). bound thyroxine (T4), free thyroxine (FT4), and triiodothyronine (T3) were measured by RIA in the blood of 10 test subjects during a 370-day head-down tilt study and a 250-day recovery period after it. The concentrations of TTH, FT4, and T3 decreased during bed rest and did not return to norm during recovery. It can be assumed that during bed rest TTH stimulation of the thyroid gland declines, which can act as an adaptive response to lower physical load. PMID- 2214663 TI - [Changes in the rheological indicators of the blood and hemodynamics during 14 day anti-orthostatic hypokinesia]. AB - Nine essentially healthy subjects, aged 25 to 42 years, were exposed to head-down bed rest (-8 degrees). On bed rest days 3, 7 and 14 the following rheological and hemodynamic parameters were measured: blood dynamic viscosity, Caisson viscosity, yield limit, red blood cell aggregation, stroke volume, cardiac output, and total peripheral resistance. Rheological parameters were measured by means of a rotation viscosimeter at 25 degrees C +/- 0.1. Hemodynamic parameters were measured by the method of integrated rheography. Blood was withdrawn from the cubital vein. The results give evidence that dynamic and Caisson viscosity increased significantly, reaching a peak by bed rest day 14. The sequence of hemodynamic changes followed the same pattern as rheological changes. Analysis of the results shows that there is a good correlation between the above parameters, especially by bed rest day 14. Thus, it can be concluded that there is a vascular mechanism involved in the compensatory restructuring of the vascular system at the tissue level in response to blood redistribution and fluid loss during bed rest. PMID- 2214664 TI - [Study of the changes in electric parameters of the rat skin after irradiation]. AB - This paper presents the results of measuring electric parameters of the skin of rats exposed to gamma-irradiation. Skin resistance increased, especially 7 and 14 days after exposure at a dose of 8.3 Gy and 3 days after exposure at a dose of 15 Gy. Skin resistance reached its peaks 1-2 days before the onset of postradiation death of animals. The fact that skin electrical properties vary after irradiation makes it possible to use them as biological predictors. PMID- 2214665 TI - [Study of the audiogenic reactions in rats after UV-irradiation of their eyes]. AB - Female rats of the Wistar strain with a mean weight of 222 g were exposed to 96 dB sound according to L.V. Krushinsky. Their eyes were irradiated with a high UV dose in order to reveal potential disorders in high nervous activity. After 3, 7 and 35 days of exposure to UV irradiation at a dose of 10 kJ/m2 with a maximum wavelength of 302 nm the following changes were observed: the amount of "inhibited" rats grew, the latency time of I degree attacks and the duration of inhibition states increased, and the duration of seizure fits decreased. It is postulated that inhibition effects may enhance and stimulation effects may attenuate as a result of reduction of afferent pulses entering the central nervous system from the visual organ due to keratoleukoma. PMID- 2214666 TI - [Physiological characteristics of posture maintenance by dogs during immediate reaction to irradiation]. AB - The ability of dogs to maintain a vertical posture during the first hours after irradiation at a dose of 10 or 80 Gy was investigated. Two experiments were performed. In the first experiment, during 5 hours after irradiation the vector stabilogram area, peak muscle efforts and sensorimotor coordination were measured 10 times every 30 min. In the second experiment, postural responses to perturbations were measured before and after irradiation at a dose of 10 Gy. During exposure to 10 Gy maximum values of the vector stabilogram area reflected initial excitation and motor unrest, that preceded vomiting, while minimum values of the parameter were related to hypodynamia during 3-5 hours after exposure. During exposure to 80 Gy minimum values of the vector stabilogram area reflected the hypodynamic phase while maximum values were related to the phase of distinct cerebral lesions. A reliable indicator of the quality of vertical posture maintenance, that correlates with the post-irradiation quality of purposeful actions, including intermittent physical acts, or actions, requiring highly precise coordination, is the rate of posture recovery after instantaneous platform displacement. This parameter declined after irradiation, the maximum decrease being during the 4-5th hour. PMID- 2214667 TI - [Hemodynamic types in pilots and their clinical and expert-evaluation significance]. AB - At the present time two approaches to the hemodynamics types can be distinguished in the literature: some authors maintain that they are variants of the norm, while others claim that they emerge in the course of disease. The purpose of the present investigation was to study the different viewpoints and to clarity the clinical and diagnostic role of hemodynamics types in aviation medicine. Altogether 293 pilots were examined, 49 of which were essentially healthy and 244 had various cardiovascular pathologies. It was found that the percentage ratio of the hemodynamics types in the subjects with neurocirculatory dystonia of the hypertensive type, stage I hypertensive disease, myocardiodystrophy and myocarditic myocardiosclerosis was the same (p less than 0.05) as in the healthy pilots. This indicates that hemodynamics types do not originate during disease, being rather variations of the norm. During orthostatic tests some subjects exhibited transition of one hemodynamic type to the other (e. g., hyperkinetic-to eukinetic type transition, p less than 0.05); however, during the very first minute after exposure 90% of the subjects displayed their inherent types which pointed to their stability. Identification of the hemodynamics types in combination with measurement of central and peripheral circulation as well as bioelectric activity of the heart at rest and during orthostatic tests can improve the sensitivity of methods used to detect pathological changes at early stages and help to choose adequate rehabilitation procedures. PMID- 2214668 TI - [Cytogenetic effects of hyperbaric oxygenation]. AB - This paper presents cytogenetic data obtained from peripheral blood of patients who were treated with hyperbaric oxygenation (HBO) at 0.15-0.2 MPa for 40 min daily during 10 days. The patients showed a significant increase of chromosome aberrations mainly caused by chromatid and chromosome breaks. The level of induced aberrations showed individual variations. These results suggest that HBO may have an indirect effect on the genetic apparatus of human somatic cells. PMID- 2214669 TI - [Epidural and subdural recording of intracranial pressure during postural tests]. PMID- 2214670 TI - [Effect of hypergravitation on mammals during labor and nursing of their offspring]. PMID- 2214671 TI - [Protective effect of mexamine on rats exposed to electromagnetic radiation]. PMID- 2214672 TI - [Biochemical aspects of the adaptation of humans to combined effects of anti orthostatism, lowered barometric pressure and increased O2 level]. PMID- 2214673 TI - [Rosette formation in the peripheral blood of rats during hypokinesia]. PMID- 2214674 TI - [Relation between annual biorhythms of the erythrocyte number in the peripheral blood of healthy persons and the annual rhythms of the changes in solar activity]. PMID- 2214675 TI - An experimental model for advanced ovarian cancer. AB - Intraperitoneally transplanted tumors implanted and began developing with ascites in about 62% of the female rats within 4 to 6 weeks after transplantation. The tumor used in this study was an adenocarcinoma and which originated from a primary ovarian cancer in rats of the same strain (Wistar). The morphology and biological behavior of the tumor were very similar to the tumor in humans. Moreover, the preliminary results with cisplatin therapy indicate that intraperitoneal cancer corresponding to stage III or IV in the FIGO classification is a promising model for experimental therapeutic studies of common epithelial carcinoma at an advanced stage. PMID- 2214676 TI - Increased gallium-67 citrate uptake in the breast of a patient with gynecomastia. AB - Although the accumulation of Ga-67 citrate in gynecomastia has been described, no researchers have reported that Ga-67 citrate accumulates in a "doughnut" pattern. Basically, gynecomastia is due to an increase of estrogens. Since estrogens accelerate the proliferation of lactiferous ducts in the center of breast, Ga-67 citrate may accumulate in it. On the hand, prolactin increases the proliferation of the glandular lobules and the acinus. When the serum prolactin increases after child birth or renal insufficiency, the image from the accumulation of Ga-67 citrate in the breast may have a "doughnut" pattern. A patient with gynecomastia had high levels estrogens because he was being treated with an estrogen medication. He was referred for liver cirrhosis. The results of the present report indicate that the "doughnut" pattern occurs in the margin of the hyperplasic glandular lobule. PMID- 2214677 TI - Tc-99m RBC imaging for demonstrating intermittent intestinal bleeding. AB - A case of intestinal bleeding caused by multiple ulcerations near the terminal ileum is presented. Abdominal scanning with Tc-99m tagged red blood cells (Tc-99m RBC) demonstrated the intermittent bleeding in short intervals. Selective angiography did not demonstrate the bleeding site. Exploratory laparotomy showed 3 ulcers on the ileum at a site near the terminal ileum, with bleeding from one site. Tc-99m RBC abdominal scanning was very useful in this case for localization of the site of gastrointestinal bleeding before laparotomy. PMID- 2214678 TI - Abdominal scanning using autologous human red blood cells labeled with Tc-99m: detection of a horseshoe kidney. AB - A horseshoe kidney was incidentally diagnosed while performing an abdominal scan using autologous human red blood cells labeled with Tc-99m (Tc-99m RBC) on a patient with suspected gastrointestinal bleeding. This patient repeatedly tested positive on occult blood stool examinations. In the first scintigram, an increase in well-defined activity was found on the right side under the liver. This could have been caused either by bleeding of the gastric antrum or the duodenal bulb. A second abdominal scan with Tc-99m RBC revealed faint radionuclide accumulation in the shape of a horseshoe with symmetrical, well-defined activity. However, the well-defined activity decreased with time on both images, and on this basis a horseshoe kidney was diagnosed. PMID- 2214679 TI - Subcloning and trial of expression of the protein kinase catalytic domain of RSV src gene. AB - The gene of catalytic domain of the protein kinase of RSV-scr was cloned into the BamHI cloning site of translation vector pET-8c which containing T7 RNA polymerase promotor, and transformed BL21 (DE3) pLys S (Studier and Moffatt, 1986). The putative molecular weight of the protein was about 33 kd as evaluated on the basis of its nucleotide size showed the identical mobility in SDS polyacrylamide gel electrophoresis. However, yield of protein production was not high, probably, because of its instability in Escherichia coli. PMID- 2214680 TI - Coronary artery bypass surgery in the elderly. AB - In order to place the issue of CABG surgery in the elderly in a personal perspective, we have reviewed our series of 250 consecutive patients 70 years or greater in age at the time of surgery and have noted a very acceptable (3.6%) operative mortality. Good short and long term survival has been documented. A modest but important elevation of postoperative CNS morbidity has been documented and remains of concern. We have continued to offer CABG to those patients with acceptable risks who have either intractable angina, intractable ischemic heart failure and multi-vessel disease. Left main obstruction of a significant degree or those with threatening three vessel anatomy in association with a sentinel ischemic event are candidates for the CABG procedure. Substantial preoperative evaluation to include the family support substrate must be an important part of the decision process as well as open communication with concerned family members. We feel that the improved life style and enhanced survival justifies CABG in those elderly patients identified with severe coronary artery disease. PMID- 2214681 TI - Distribution of major dementias by race and sex in South Carolina. AB - Preliminary data from the newly implemented Registry for dementing illnesses was used to examine the distribution of four types of dementia in black and white residents of South Carolina. The data for 1464 subjects were abstracted by field research nurses in state mental health facilities. Overall, 649 patients (44.3%) were black and 765 (52.3%) were white. Women comprised 53.8% of all cases of dementia in this study. The overall distribution included 66% Alzheimer's disease (AD), 12% multi-infarct dementia (MID), 10% alcoholic dementia (ALC), nine percent other-medical and three percent other-unspecified. Though the proportion of blacks does not exceed one-third of the total population of S.C., blacks comprised 44.3% of all cases of dementia. AD accounted for 79% of all cases of dementia in women, but only 51% of such cases in demented men, who showed an apparent preoponderance of MID and alcoholic dementia. The frequency distribution of MID was equal in blacks and whites. Educational level had no discernible effects. Though not directly comparable, these preliminary findings are similar to those of the Copiah County Study, including a higher frequency of AD with advancing age. PMID- 2214682 TI - The need for an Alzheimer's disease patient registry in South Carolina. AB - There has been considerable interest in establishing a statewide registry of Alzheimer's disease patients. The need for such a registry, how it could be effectively organized, and the potential benefits from such a registry are discussed. The current status of the South Carolina Registry for Dementing Illnesses is reported. PMID- 2214683 TI - First among the C's. PMID- 2214684 TI - New found feelings as to our place and obligations in patient contact (care) PMID- 2214685 TI - Human immunodeficiency virus and the surgeon. AB - To assess the exposure risks for surgeons and nurses treating HIV infected patients at the Medical University Hospital and the Charleston Memorial Hospital, a retrospective review of HIV positive patients who underwent surgical procedures from 1985-1988 was undertaken. During that period, 150 patients tested positive for HIV of which 30 (20%) underwent 19 surgical procedures. The prevalence of HIV infected patients at our institution has been increasing over the last two years. 5.3% of the patients tested were positive for the virus. Evidence of drug abuse was not a predictive factor of HIV infection but homosexuality was present in 57% of our patients. The mean age of the surgical group was 34 years. Seventy-three percent of the patients underwent minor operations and 27% had major surgical procedures. Almost half of the operations were performed to treat an AIDS-related complication or as a diagnostic aid in the workup of the AIDS patient. Major operations performed were for treatment of a co-morbid condition not related to the HIV infection. Only two patients had operations for trauma. Operative mortality was 10% but no death was directly related to surgical intervention. In addition to universal precautions in the pre and postoperative period, operating room personnel must follow established protocols in the conduct of the operation to ensure the safety of all staff. PMID- 2214686 TI - Recent trends in neonatal mortality in South Carolina. AB - This study examines some of the primary factors responsible for the decline in South Carolina's neonatal mortality rate during the 1980s. Essentially all of the observed decline between 1980-82 and 1984-86 could be attributed to improved birthweight-specific survival rather than improvements in the infant birthweight distribution. Improved survival of 500-1,499 g infants accounted for 64% of the decline in white neonatal mortality and 70% of the decline among blacks. Also, during this period, the percentage of 500-1,499 g infants delivered at Level III hospitals increased significantly for both race groups. Comparisons with other southeastern states suggest that further reductions in South Carolina's neonatal mortality rate are possible through continued efforts aimed at improving birthweight-specific survival. Existing state-supported programs such as regional perinatal referral networks and the High Risk Channeling Project will continue to play an important role in maintaining the decline in the state's neonatal mortality rate. PMID- 2214687 TI - Compression plate osteosynthesis for the treatment of mandibular fractures. PMID- 2214688 TI - Anxiety and the human family unit: a perspective. PMID- 2214689 TI - HIV, surgeons, and ... all of us. PMID- 2214690 TI - Treatment of industrial wounds with DuoDERM Bordered: a report on medical and patient comfort aspects. AB - In a prospective study 30 patients with minor industrial wounds were treated with DuoDERM Bordered. Medical aspects, patient comfort and the possibility of continuing activities of daily life are described in this report. PMID- 2214691 TI - Medical kits for business travellers. AB - A survey of occupational physicians of the Food Industry Medical Officers Group was undertaken to establish details of medical kits supplied by their organizations to business travellers. The most common approach was an in-house medical kit with instructions emphasizing self treatment of the common ailments of travellers such as motion sickness, sleeplessness, diarrhoea, indigestion and headaches. The majority of kits included a small supply of needles, syringes, IV cannulae etc either in a commercial 'Aids Kit' or as inhouse supplies. Antimalarials were provided either as a standard kit item or as required. About half provided antibiotics for the self treatment of infections. Very few provided a telephone number for use in the event of medical emergencies. A standard medical kit specification is proposed. PMID- 2214692 TI - Simulator sickness in an army simulator. AB - Simulator sickness describes a symptom reported by aircrew during or after flight simulator training. Some features are common to motion sickness but others, which are unusual during real flight, are believed to result specifically from the simulator environment. This paper describes the results of a questionnaire study examining the incidence and factors influencing simulator sickness in any army training system. Case histories are described and conclusions drawn with respect to health and safety, training and the effect on flight operations. One hundred and fifteen aircrew were registered in the questionnaire study. Data were collected from a history questionnaire, a post-sortie report and a delayed report form. Sixty-nine per cent of aircrew gave a history of symptoms in the simulator and 59.9 per cent experienced at least one symptom during the study period although few symptoms were rated as being other than slight. Only 3.6 per cent of subjects reported symptoms of disequilibrium. Comparative analysis of the results was performed after scoring symptoms to produce a sickness rating. This showed: association between simulator-induced sickness and greater flying experience; adaptation to the simulator environment; a history of sea sickness may predict susceptibility to simulator sickness; and no association of crew role and simulator sickness. Although some authorities believe simulator sickness to be a potential flight safety hazard there was little evidence from this study. Guidelines for the prevention of the problem are presented now that many factors have been identified. A general policy to 'ground' aircrew for a period following simulator training is not necessary, but severe cases should be assessed individually. PMID- 2214694 TI - Classification of audiometric results. PMID- 2214693 TI - Health problems among spice grinders. AB - Sixty-one male spice grinders from 14 factories were studied to determine if they had any skin problems, respiratory symptoms or hearing loss associated with their work. All subjects were interviewed and examined. Audiometric examinations were arranged for those with significant noise exposure. Assessments of dust and noise levels were conducted. Symptoms of upper respiratory tract irritation, such as sneezing and runny nose, during work were experienced by 49.2 per cent of workers. These symptoms were maximal in the first few weeks of employment in spice grinding and did not recur in half of the affected workers. Over 26 per cent of the workers experienced a warm or burning sensation of the skin when grinding chili or pepper. None of the spice grinders had symptoms or evidence on physical examination of allergic skin disease or asthma. Noise-induced hearing loss was detected in 21 per cent of the workers examined but none had severe disabling deafness. Dust levels ranged from 0.03 to 0.82 mg/m3, with a mean value of 0.15 mg/m3. Noise exposure was significant, with levels of between 87 and 98 dBA. Control measures to reduce the noise and dust exposure are discussed. PMID- 2214695 TI - Body counting and behaviour. PMID- 2214696 TI - Death of the LD50. PMID- 2214697 TI - Peer review audit in occupational medicine. AB - There is an increasing awareness of the need for medical audit. A method for peer review medical audit that has been applied to two large industries is described. Occupational physicians act as auditors of randomly selected case notes from their colleagues' list of consultations using an agreed proforma as a guideline. Open discussion by the occupational physician of the auditor's comments identifies needs, such as for a change on policy or further education. Implementation of the agreed changes and subsequent review completes a cycle of audit. PMID- 2214698 TI - Resource needs of an occupational health service to accommodate a hepatitis B vaccination programme. AB - The administrative, organizational and clinical commitment of an occupational health department to implement the DHSS recommendation for a hepatitis B vaccination programme for the health care workers in a District General Hospital was reviewed to evaluate the resource implications needed to accommodate the additional workload. The deficiencies observed in the existing DHSS guidance in implementing the plan are described. It is suggested that the Department of Health, while making future recommendations for vaccination, should be more precise in identifying those at risk, in describing the desired titre to be achieved after vaccination, and in describing the follow-up plan for those who accept the vaccination, those who refuse and those who do not seroconvert. The recommendation should describe the commitment of the Health Authorities and must include recommendations for appropriate and adequate resources to support such a programme. Vaccination for 1000 employees at risk required 4000 additional consultations necessitating 16 additional hours of occupational health commitment per week. Eighteen months after initiating the vaccination programme, 677 employees had accepted the vaccine. After receiving 3 vaccines 508 (75 per cent) recipients had protective seroconversion (anti-Hbs greater than 100 I.U.) and a further 61 (9 per cent) converted after the 4th injection, thereby offering protective immunity to 84 per cent of the recipients. During the period 84 (12.4 per cent) were lost to follow-up. Recommendations have been made to accommodate the additional commitment through the vaccination programme to standardize our care and prevent disruption of the existing service. PMID- 2214699 TI - Infection risks in hospital staff from blood: hazardous injury rates and acceptance of hepatitis B immunization. AB - A questionnaire survey of 1800 clinical health care staff was undertaken to determine hazardous injury rates and uptake of hepatitis B vaccination. The overall sharps injury rate was 116 injuries per 100 staff per year. Full-time doctors had the highest rates. Surgical procedures were the commonest cause of accidental injury (58 per cent) and 30 per cent of all sharps injuries were attributable to careless handling. Injuries caused by bites and scratches from patients occurred mainly in nurses and auxilliaries in psychiatric and geriatric wards (115/100 staff per year). Twenty-four per cent of respondents had received a full course of hepatitis B vaccine and 51 per cent of the remainder were planning to have, or were in the process of receiving, a course. The most frequent reason given for not being vaccinated was lack of information about vaccination. This survey reveals injury rates higher than those observed in previous reports, particularly in doctors, and shows a need for more information and advice about hepatitis B infection and vaccination to be targeted to health care workers at risk. PMID- 2214700 TI - An investigation of the neurobehavioural effects on workers exposed to organic solvents. AB - Forty-five workers exposed to the solvents xylene and toluene in varnishing processes in a major heavy electrical industry were studied to find the effect of this exposure on different parameters of behaviour. These were immediate and delayed memory, visual ability, visual learning and psychomotor ability. The findings were compared with those from subjects who were not exposed. Immediate memory and delayed memory were affected among both directly and indirectly exposed workers as compared with those in the controls which remained unaffected. Visual intelligence and memory were most affected by exposure. Psychomotor ability was significantly affected among the directly exposed workers, as compared with the occasionally exposed group which did not show any significant difference from the control workers. PMID- 2214701 TI - Food poisoning--a major threat to airline operations. AB - In the spring of 1984, British Airways was involved in a major food poisoning outbreak which affected nearly 1000 passengers, aircrew and ground personnel. The operational impact was worldwide and could have resulted in the cessation of the airline's day-to-day operations. The investigation paralleled a major aircraft disaster in the number of national and international agencies involved and in the variety of disciplines engaged. Although the causative organism was rapidly identified (salmonella), and its introduction into the food chain proved to be a key factor, the scale of the outbreak was the result of an interaction of other factors. As with a major aircraft accident, none of the factors alone would have caused the near disaster that occurred. PMID- 2214702 TI - Cell biomechanics. PMID- 2214703 TI - Cell biomechanics: a brief overview. AB - In this issue of the Journal of Biomechanical Engineering, there are eleven papers and one technical brief in the general area of "Cell Biomechanics." In general, the work in these papers focuses on measuring and characterizing the mechanical and adhesive properties of cells and membranes. Included are studies of lipid membranes, erythrocytes, endothelial cells, and neutrophils. Characterizing and measuring the properties and behavior of cells in both passive and active states present a major challenge to investigators in this field. In this paper in the comments to follow, a simple overview of the field is presented and the principles and techniques used in the studies of cell biomechanics are discussed. PMID- 2214704 TI - Bilayer membrane bending stiffness by tether formation from mixed PC-PS lipid vesicles. AB - Recently, a new approach to measure the bending stiffness (curvature elastic modulus) of lipid bilayer membrane was developed (Biophys. J., Vol. 55; pp. 509 517, 1989). The method involves the formation of cylindrical membrane strands (tethers) from bilayer vesicles. The bending stiffness (B) can be calculated from measurements of the tether radius (Rt) as a function of the axial force (f) on the tether: B = f.Rt/2 pi. In the present report, we apply this method to determine the bending stiffness of bilayer membranes composed of mixtures of SOPC (1-stearoyl-2-oleoyl phosphatidyl choline) and POPS (1-palmitoyl-2-oleoyl phosphatidyl serine). Three different mixtures were tested: pure SOPC, SOPC plus 2 percent (mol/mol) POPS, and SOPC plus 16 percent POPS. The bending stiffness determined for these three different lipid mixtures were not significantly different (1.6-1.8 x 10(-12) ergs). Because POPS carries a net negative charge, these results indicate that changes in the density of the membrane surface charge have no effect on the intrinsic rigidity of the membrane. The values we obtain are consistent with published values for the bending stiffness of other membranes determined by different methods. Measurements of the aspiration pressure, tether radius and the tether force were used to verify a theoretical relationship among these quantities at equilibrium. The ratio of the theoretical force to the measured force was 1.12 +/- 0.17. PMID- 2214705 TI - Extensional recovery of an intact erythrocyte from a tank-treading motion. AB - Normal human erythrocytes suspended in shear flow are stretched into quasi ellipsoidal forms while their membranes rotate smoothly (tank-treading). Following abrupt cessation of shear the cells recover their discoidal shapes approximately exponentially, in the manner of a Kelvin-Voigt (K-V) solid. To test the hypothesis that the recovery process is membrane-controlled, the effects of initial deformation, cytoplasmic viscosity and membrane surface-to-volume ratio were studied. It was concluded that the membrane dynamics dominates the transient shape recovery, and that the characteristic recovery time is dependent on the initial deformation. Hence, the usual simplified analysis based on retraction of a plane sheet of K-V material with constant moduli appears to be an inadequate treatment of transient whole cell recovery. PMID- 2214706 TI - Effects of cell lysis on the rheological behavior of red blood cell suspensions. AB - Rheological studies of lysed cell suspensions are performed with a magneto acoustic ball microrheometer. Two methods for lysing the cells are developed in order to provide cell volume concentrations identical to control intact cell suspensions. The first uses a freeze-thaw technique and the second uses sonication. It is found that cell suspensions disrupted by sonication have a lower viscosity than intact suspensions, whereas cell suspensions lysed by the freeze-thaw method exhibit a higher viscosity. Sonication is discovered to have a detrimental impact on the cell membrane, and to cause complete destruction of the cell membrane structure. Measurements of the steady state viscosity show that indeed the presence of the membrane is not detected, and that what is measured is mainly the viscosity of the hemoglobin solution. On the other hand, freeze-thaw results indicate that at least two phenomena occur. The first phenomenon, occurring during the first freeze-thaw cycle, produces an increase in viscosity and in viscoelasticity. The second one, taking place after subsequent freeze-thaw cycles, induces a decrease in the bulk rheological properties. Several possible mechanisms are presented to explain the observed phenomena. PMID- 2214707 TI - Application of the micropipette technique to the measurement of cultured porcine aortic endothelial cell viscoelastic properties. AB - The viscoelastic deformation of porcine aortic endothelial cells grown under static culture conditions was measured using the micropipette technique. Experiments were conducted both for control cells (mechanically or trypsin detached from the substrate) and for cells in which cytoskeletal elements were disrupted by cytochalasin B or colchicine. The time course of the aspirated length into the pipette was measured after applying a stepwise increase in aspiration pressure. To analyze the data, a standard linear viscoelastic half space model of the endothelial cell was used. The aspirated length was expressed as an exponential function of time. The actin microfilaments were found to be the major cytoskeletal component determining the viscoelastic response of endothelial cells grown in static culture. PMID- 2214708 TI - Rapid flow of passive neutrophils into a 4 microns pipet and measurement of cytoplasmic viscosity. AB - Neutrophils from five different individuals are isolated with a density separation technique. A total of 151 unactivated (passive) cells are rapidly aspirated at constant suction pressure and at room temperature into a pipet with a diameter of 4 microns. The suction pressures in excess of an initial yield threshold are 0.5, 1 and 2 kPa and are comparable to those encountered in the microcirculation. These pressures are well in excess of the small suction pressure of approximately 20 Pa that is required to form a static hemispherical bump on the cell. At a given aspiration pressure, the leading edge of an individual cell is "tracked" as it flows into the pipet. A theory based on the flow of a Newtonian liquid from either a hemisphere or a spherical segment into a cylinder is used to model the entry process. Both theory and experiment show that during most of the entry process the leading edge of the cell moves at a nearly constant velocity with a rapid acceleration at the end. For cells from five different individuals at the three different excess aspiration pressures, Newtonian theory gives a cytoplasmic viscosity of 135 +/- 54 Pa.s and overall entry times of 3.3s (0.5 kPa), 1.6s (1 kPa) and 0.82s (2 kPa). These results and those of Evans and Yeung at lower aspiration pressures indicate that the complex cytoplasm inside unactivated neutrophils behaves as a nearly Newtonian fluid with a viscosity on the order of 10(2) Pa.s over almost a two order of magnitude range in aspiration pressure and, thus, rate of deformation. PMID- 2214709 TI - The behavior of human neutrophils during flow through capillary pores. AB - The passage times of individual human neutrophils through single capillary-sized pores in polycarbonate membranes were measured with the resistive pulse technique, and results were compared to those obtained from the micropipette aspiration of entire cells. Pore transit measurement serves as a useful means to screen populations of cells, and allows for protocols that measure time dependent changes to the population. Neutrophils exhibited a highly linear pressure/flow rate relationship at aspiration pressures from 200 Pa to 1,500 Pa in both the pore and pipette systems. Cellular viscosity, as determined by the method of Hochmuth and Needham, was 89.0 Pa.s for the pore systems and 134.9 Pa.s for the pipette systems. These results are in general agreement with recent values of neutrophil viscosity published in the literature. Extrapolation of the observed linear flow response revealed an apparent minimum pressure for whole cell aspiration significantly above the threshold pressure predicted by Evans' liquid drop model. However, whole cell aspiration was achieved in both the pore and pipette systems at pressures below this extrapolated minimum, although the calculated cellular viscosity was greatly increased. The implications of these two regimes of cell deformation is unclear. This behavior could be explained by shear thinning of the material in the cell body. However the origin of this phenomenon may be in the cortical region of the cell, which exhibits an elastic tension that may be deformation rate dependent. PMID- 2214710 TI - Determination of cellular mechanical properties by cell poking, with an application to leukocytes. AB - In this paper we review the cell-poking technique as an approach for investigating the mechanical properties of living cells. We first summarize the rationale for the technique and the mainly qualitative results obtained so far. Then we provide a technical description of the instrument as it is configured at present. This is followed by a discussion of the current status of analytical results available for interpreting cell-poking measurements. In the final section we apply these results to an analysis of unmodulated and modulated lymphocytes and neutrophils, and conclude that the mechanical response of these leukocytes to indentation is not consistent with simple models developed by previous investigators on the basis of micropipette-aspiration experiments. PMID- 2214711 TI - Passive deformations and active motions of leukocytes. AB - The purpose of this paper is to review the development of continuum mechanics models of single leukocytes in both passive deformations and active motions and to indicate some future directions. Models of passive deformations describe the overall rheological behavior of single leukocytes under externally applied forces and predict the average mechanical properties from experimental data. Various "apparent" viscoelastic coefficients are obtained depending on the models assumed and the types of test used. Models of spontaneous motions postulate active driving mechanisms which must be derived internally from the cell itself and probably have different bases for different kind of motions. For pseudopod protrusion on leukocytes, energy transduction from chemical potential to mechanical work associated with actin polymerization at the tip of the projection is assumed to supply the motive power. For pseudopod retraction, active contraction due to actin-myosin interaction is assumed to be the driving force. The feasibility of the hypotheses are tested via numerical examples and comparison of the theoretical results with experimental measurements. PMID- 2214712 TI - Kinematics of cytoplasmic deformation in neutrophils during active motion. AB - A procedure is proposed to measure the cytoplasmic deformation in active motile neutrophils in the form of cytoplasmic strains and strain rates. Three neighboring microspheres in a local region of the cytoplasm serve as markers for local motion. Their positions are tracked by means of a high resolution light microscope and serve to compute nonlinear measures of strains and strain rates together with the principal strains and principal directions. Active neutrophils exhibit large cytoplasmic strains both during periodic pseudopod projections and during continuous locomotion in a polarized shape. The cytoplasmic motion is often synchronized with the whole cell deformation. The local cytoplasmic strains exceed the strains estimated for the whole cell and are not reversible except in some cases of single pseudopod projections. Large strains are observed both in attached and freely suspended cells. Strain rates are relatively constant but show an increase during the pseudopod retraction phase. Local cytoplasmic strains in neutrophils are inhomogeneous and reach large values during passage of the contraction rings. Neutrophils rendered passive by treatment with cytochalasin or EDTA show a random motion of microspheres with much smaller displacements. These observations suggest that the cytoplasm of active neutrophil exhibits large cytoplasmic strains and strain rates in the absence of an external stress resulting in a high degree of intracellular mixing. The proposed technique may be applied to a wide range of problems in cell biology. PMID- 2214713 TI - Cell-cell, cell-substrate adhesion: theoretical and experimental considerations. AB - Cell-cell adhesion plays a fundamental role in tissue and organ development, cell mediated immunity and blood flow. In the present study a micro-mechanical model of specific adhesion is presented. Analytical expressions are derived for the adhesive energy density (gamma) at zero speed of peeling for the cases of immobile (trapped) as well as laterally mobile bonds. It is shown that gamma increases in both cases with the increasing density of bonds and with the binding of affinity of unstressed bonds. In the case of laterally mobile bonds gamma also increases with the extent of peeling. The analytical results are shown to be valid whether or not one takes into account of the bending stiffness of adhering membranes. It is also shown that gamma does not depend on the functional form of bond elasticity. The effect of the speed of peeling on the number density distribution of attached bonds is considered next. Numerical solutions for the energy required to separate conjugated cell pairs are presented. The theoretical predictions are then used to analyze experimental data on red cell aggregation and adhesion between a cytotoxic-T cell and its target cell. The results show that the binding affinity of unstressed bonds and their number density before conjugation can be obtained from data on slow peeling of cell-pairs. The information on the diffusivity of bonds, their stiffness and their rates of attachment and detachment are more difficult to obtain, requiring a set of experiments with increasing rates of separation (conjugation) of cell-pairs. PMID- 2214714 TI - Intermediate filaments may prevent buckling of compressively loaded microtubules. PMID- 2214715 TI - Forward and backward running waves in the arteries: analysis using the method of characteristics. AB - The one-dimensional equations of flow in the elastic arteries are hyperbolic and admit nonlinear, wavelike solutions for the mean velocity, U, and the pressure, P. Neglecting dissipation, the solutions can be written in terms of wavelets defined as differences of the Riemann invariants across characteristics. This analysis shows that the product, dUdP, is positive definite for forward running wavelets and negative definite for backward running wavelets allowing the determination of the net magnitude and direction of propagating wavelets from pressure and velocity measured at a point in the artery. With the linearizing assumption that intersecting wavelets are additive, the forward and backward running wavelets can be separately calculated. This analysis, applied to measurements made in the ascending aorta of man, shows that forward running wavelets dominate during both the acceleration and deceleration phases of blood flow in the aorta. The forward and backward running waves calculated using the linearized analysis are similar to the results of an impedance analysis of the data. Unlike the impedance analysis, however, this is a time domain analysis which can be applied to nonperiodic or transient flow. PMID- 2214716 TI - Estimation of the rotational undamped natural frequency of bileaflet cardiac valve prostheses. AB - The angular momentum balance is solved numerically for a size 29 mm CarboMedics prosthetic heart valve. The lift force is estimated from potential flow theory, while the drag force is estimated from the lift force and a blunt body empiricism. Buoyancy and gravitational effects are calculated based on the assumption of homogeneous leaflets. Other assumptions include uniform flow, negligible friction at the pivot axis, negligible viscous damping and fluid inertance, and a symmetry flow condition. Oscillations are predicted in the opening dynamics in the range of 2-25 Hz, for flow rates through one-half of the orifice in the range of 0.1-10.0 l/min. The frequency of these oscillations is dependent upon the orientation of the leaflet in relation to the gravitational field and the magnitude of the flow rate. In vivo and in vitro measurements by other investigators demonstrate similar effects of gravity and flow rate, with flutter frequencies of the order of 10-100 Hz. Excitation frequencies, based on vortex shedding, are estimated to be of the order 2-200 Hz, for the range of flow rates of the theoretical model. These results suggest that the natural frequency of this rotational second order system may, in theory, be a contributing factor to the flutter observed in bileaflet cardiac valve prostheses. The clinical significance of this finding is yet to be established. PMID- 2214717 TI - Determination of a constitutive relation for passive myocardium: I. A new functional form. AB - The specific aim of this study is to determine a constitutive relation for non contracting myocardium in terms of a pseudostrain-energy function W whose form is guided by both theory and experiment. We assume that the material symmetry of myocardium is initially and locally transversely-isotropic, and seek a W which depends upon only two coordinate invariant measures of the finite deformation. The specific functional form of such a W is inferred directly from experimental protocols in which one invariant is held constant while the other is varied, and vice versa. On the basis of data from families of these "constant invariant" tests on thin slabs of myocardium taken from the mid-walls of six canine left ventricles, we propose a new polynomial form of W containing only five material parameters. PMID- 2214718 TI - Determination of a constitutive relation for passive myocardium: II. Parameter estimation. AB - In the first paper of this series, we proposed a new transversely isotropic pseudostrain-energy function W for describing the biomechanical behavior of excised noncontracting myocardium. The specific functional form of W was inferred directly from biaxial data to be a polynomial function of two coordinate invariant measures of the finite deformation and five material parameters. In this paper, best-fit values of the material parameters are determined from biaxial data using a nonlinear least-squares regression. These values of the parameters are shown to be well-determined, and the final constitutive relation is shown to have good predictive capabilities. Since the proposed constitutive relation describes much broader classes of in-vitro biaxial data than previously proposed relations, it may be better applicable to analyses of stress in the passive heart. PMID- 2214719 TI - Design optimization of a prosthesis stem reinforcing shell in total hip arthroplasty. AB - The use of a perforated, titanium funicular shell to support the proximal femoral cortex in total hip arthroplasty was evaluated with the aid of both analytical and numerical techniques. The principal interactions between the femoral cortex, the metal shell, the implant stem and the acrylic bone cement were modeled using beam on elastic foundations theory and two-dimensional elasticity theory. Subsequent formulation of this model as a nonlinear design optimization problem enabled the determination of the dimensions of the implant and reinforcing shell which minimized an objective function based on a simplified material failure criterion. Two cases were examined, each with two cervico-diaphyseal angles: case A: with a rigid contact between a proximal prosthesis collar and the calcar femorale and case B: no collar contact (a collarless prosthesis or post-operative loosening). Case A achieved an optimal solution at a stem diameter 11-23 percent of the cortex inner diameter, a stem length to diameter ratio of 12-40, shell diameter 22-53 percent and thickness 0.2-7.2 percent of the cortex inner diameter and thickness, respectively. Case B achieved an optimal solution at a stem diameter 67-92 percent of the cortex inner diameter, length to diameter ratio of 4-6, and no shell. In case A the collar support makes the type of internal fixation unimportant, while in the more realistic case B, the shell is not recommended. PMID- 2214720 TI - Nonlinear analysis of intervertebral disk under dynamic load. AB - This study pertains to the response of intervertebral joint under dynamic axial load. The numerical model represents two vertebral bodies with an interposed disk and uses three-dimensional elements. A transversely isotropic material law is adopted for cortical bone and an isotropic law for cancellous bone. Annulus collagen fibers are modelled using truss elements with no compressive resistance. The disk material is assumed hyperelastic, using a mixed finite element approach, allowing a representation of the disk involving the incompressibility characteristics for the material. The analysis considers finite displacement and strain fields under dynamic load. Intensity, trend and distribution of loads on the vertebral body are deduced from the literature. The problem is investigated with reference to different compressibility levels of disk material related to disk degenerationn phenomena. PMID- 2214721 TI - The joint distribution problem with multiple articular contact forces. AB - The single joint distribution problem with two or more unknown bony contact forces is considered, and an optimal solution procedure free of ad hoc assumptions is described. If two bony contact forces are present, a strictly muscle force dependent equality constraint exists that allows for initial independent estimation of muscle forces, followed by unique estimation of all bony contact force components perpendicular to the straight line connecting their known points of application. However, if three or more bony contact forces are present, no strictly muscle force dependent equality constraint exists, solution separability is lost, and optimal muscle and bony contact forces are obtained simultaneously. PMID- 2214722 TI - Impedence osteography: clinical applications of a new method of imaging fractures. AB - Fracture healing usually proceeds without difficulty. However, the diagnosis of delayed or non-union is not simple and can present difficulties in management. Normal fracture healing is briefly reviewed along with some methods of assessing the progress of union. The results of using the technique of impedence osteography in a preliminary study of fracture healing are presented. These indicate that the technique can clearly show a fracture and differentiate between normal bone, a united fracture and a non-union. PMID- 2214723 TI - Prosthetic heart valves: waveform comparisons and average value disposition for pulsatile flow in vitro. AB - With the development of the in vitro testing of heart valves, the standardization of the test methods becomes increasingly important and they should also be improved continuously. This paper discusses the problems of waveform comparison and average value dispositions. In the pulsatile model driven by pneumatics, the pressures before and after the valve, and the flow through it, are measured as three one-dimensional variates. The mean values are calculated according to the FDA and the ISO. A comparison and analysis of experimental waveforms indicate that, for basically the same ranges of pressures and flow rate, the flow curves of different types of valve are clearly different. The mean values and the waveforms in the time domain should be taken into consideration synthetically so that the pusatile characteristics of the valve can be more completely reflected. Using numerical filtering methods to treat the waveforms allows for better comparisons between the measured results taken from the different devices. By means of the constellation graphical method for treating mean values as multivariates, it is feasible to classify the valves and to judge their qualities under conditions of pulsatile flow. PMID- 2214724 TI - Stress analysis of the proximo-medial femur after total hip replacement. AB - Stress-induced bone loss in the proximo-medial femur has been identified as a factor leading to loosening in the artificial hip joint. In an effort to develop a quantitative understanding of the stress distribution that causes bone loss, axial and hoop stresses in the medial calcar of the femur have been determined after total hip replacement, using finite element stress analysis. Stress distributions for a high and a low Young's modulus prosthesis material are compared for both collared and uncollared prosthesis designs. The use of a low modulus material, and of a collar, are predicted to be advantageous, giving rise to proximo-medial stress patterns similar to those of the normal, intact femur. PMID- 2214725 TI - A microcomputer-based video vector system for clinical gait analysis. AB - A microcomputer-based video vector system has been developed to display the resultant ground reaction force vector on a television image of the subject in real-time. For each television field the force platform signals are acquired and processed and the resultant force vector superimposed on the video image of the walking subject. The force platform results are stored on disc and the composite video signals recorded on video tape for further analysis. The system is easy to set up and use and the results can be readily interpreted. The external moments produced at the joint centers by the ground reaction forces can be observed visually and, if required, quantification of the external moments can be achieved following data collection. The spatial resolution of the system is 0.342% vertically and 0.156% horizontally. The force vector visualization technique has routine applications in orthotics and prosthetics. It is also a useful technique for the teaching of biomechanics. PMID- 2214726 TI - Automated three-dimensional finite element modelling of bone: a new method. AB - Three-dimensional finite element stress analysis of bone is a key to understanding bone remodelling, assessing fracture risk, and designing prostheses; however, the cost and complexity of predicting the stress field in bone with accuracy has precluded the routine use of this method. A new, automated method of generating patient-specific three-dimensional finite element models of bone is presented--it uses digital computed tomographic (CT) scan data to drive the geometry of the bone and to estimate its inhomogeneous material properties. Cubic elements of a user-specified size are automatically defined and then individually assigned the CT scan-derived material properties. The method is demonstrated by predicting the stress, stain, and strain energy in a human proximal femur in vivo. Three-dimensional loading conditions corresponding to the stance phase of gait were taken from the literature and applied to the model. Maximum principal compressive stresses of 8-23 MPa were computed for the medial femoral neck. Automated generation of additional finite element models with larger numbers of elements was used to verify convergence in strain energy. PMID- 2214727 TI - Mechanical characteristics of micro-switches adapted for the physically disabled. AB - The object of this study was to measure the mechanical characteristics of several commonly used adapted switches in order to demonstrate the feasibility of collecting quantitative descriptions of switch performance. A stepping motor was used to drive a digital micrometer vertically towards the tested switch and proving-ring strain gauges recorded the operating force. Measures of activation and deactivation forces, travel and switch compliance were compared; several clinical examples illustrate the functional application of these results. It is anticipated that this information will permit clinicians to prescribe switches in a more accurate manner. PMID- 2214728 TI - Measured and modelled static and dynamic axial trunk torsion during twisting in males and females. AB - Study of the mechanics of trunk twisting is of special interest given epidemiological evidence linking occupational twisting to increased incidence of low back pain. An anatomically detailed, three-dimensional model of the trunk (rib cage, pelvis, five lumbar vertebrae and 50 muscles), was used to predict maximum axial trunk torque. Predicted axial torques were compared with measured torques. Thirty-one (10 male and 21 female) subjects performed maximum effort isometric twisting exertions, at 0 degrees of twist and +/- 30 degrees of twist together with dynamic exertions, at 30 degrees s-1 and 60 degrees s-1. Females were able to generate approximately two-thirds of the torque of males (males, 97Nm; females 60Nm, isometric at 0 degrees). When the trunk was prerotated to 30 degrees, subjects were able to generate greater torque when the effort was toward the 0 degree position (approximately 105Nm by males and 68Nm by females). Experimental data indicated that velocity of rotation and amount of twist are important modulators of axial torque. Changes in muscle length were demonstrated to be minimal from model output as most muscle length changes during a twist from 0 degrees to 30 degrees, measured between the pelvis and the shoulder harness, were less than 1%, although some portions of the abdominal obliques underwent a length excursion of 5%. The small changes in the individual muscle force components that contribute to twist, i.e. the muscle unit vector about the axial twist axis and its moment arm that change as a function of twisted position, do not entirely account for the measured differences in torque, suggesting that additional mechanisms influence axial torque generation. PMID- 2214729 TI - Influence of magnetic fields on calcium salts crystal formation: an explanation of the 'pulsed electromagnetic field' technique for bone healing. AB - In the search for a mechanism by means of which a magnetic field deparalyses non unions and enhances bone tissue formation, the influence of continuous magnetic fields on the formation of calcium phosphate crystal seeds has been investigated. From this perspective, an explanation is given of a working mode in conventional equipment for pulsed electromagnetic field treatment; this is compared with multifunction equipment. PMID- 2214730 TI - Symmetry of FES responses in the lower extremities of paraplegic patients. AB - Due to natural or artificial obstacles, gait is a less automatic and periodic process than it would appear when studying normal walking on the level. Pre programmed functional electrical stimulation (FES) sequences, therefore, do not appear to be a suitable approach to the control of multichannel electrical stimulators in the restoration of paraplegic walking. Walking in paraplegic subjects must be, to a large extent, under voluntary control. To lessen the burden of this control, the symmetry of walking can be taken into account. Symmetric motion of the legs requires symmetric FES actuation. Symmetry of FES responses was studied in a group of 10 paraplegic subjects who had all undergone the FES training program. Recruitment curve, fatigue index and twitch delay were assessed. An average 80% symmetry was found in all parameters measured, thus allowing a reduction of complexity of control approach for FES locomotor aids. PMID- 2214731 TI - Simulation study of the fluid dynamics of aorto-coronary bypass. AB - It is well known that local fluid dynamic phenomena are the main factors affecting the failure of aorto-coronary bypass procedures. With the aim of investigating the influence of bypass geometrical parameters on the fluid dynamics around the anastomosis, a two-dimensional finite element model of a stenosed coronary artery with an aorto-coronary bypass has been developed. The geometrical parameters on which the study focused were the degree of coronary stenosis, the bypass diameter and the bypass angle. The fluid dynamic equations have been solved using the finite element method. The results show the development of a recirculation area immediately downstream of the anastomosis and its relationship with the investigated parameters. In particular, the magnitude of the recirculation increases with the bypass angle, the bypass diameter and the degree of coronary stenosis. PMID- 2214732 TI - Study of normal and cancerous urine using photoacoustic spectroscopy. AB - Photoacoustic spectroscopy (PAS) is a valuable technique, increasingly applied in clinical and biological analysis. Light absorption properties of urine and body tissue can be obtained more easily by the PAS technique because of its high sensitivity, than by the conventional optical techniques. By observing their absorption properties it is possible to diagnose some diseases and in this study we have used PAS to assess cancerous changes in urine and tissue. Three groups were studied: normal individuals; patients with cancer; and patients with cancer and subsequent inflammation; and the characteristic light absorption peaks obtained for a certain band (240-420 nm). These results were compared with the clinical diagnosis and proved consistent and reliable for the diagnosis of urinary tract cancer subsequently confirmed by operation. This method will probably be a useful tool for the early clinical diagnosis of cancer of the urinary system. PMID- 2214733 TI - Simulation of coronary circulation with special regard to the venous bed and coronary sinus occlusion. AB - The vascular beds of the left circumflex and the left anterior descending coronary arteries are modelled by means of coupled differential equations that consider an arterial, a capillary and a venous section. In a stepwise procedure, experimental data from normal coronary perfusion and coronary sinus occlusion are used to assess the model parameters. For venous distensibility, a non-linear form of pressure-volume relationship proved vital to reproduce the characteristics of the rise in venous pressure after the onset of coronary sinus occlusion. Numerical integration was carried out for normal perfusion and for coronary sinus occlusion, yielding time courses of flows, volumes and pressures within large coronary arteries, capillaries and coronary veins. Coronary sinus occlusion reduces total mean flow by 18% and divides intramyocardial flow between the capillaries and the veins into a forward component of 3.03 mls-1 and a backward component of -1.54 mls-1. This result represents a prediction for a haemodynamic quantity which is therapeutically important but inaccessible to measurement. Varying degrees of systolic myocardial squeezing are studied to display the impact of myocardial contractility and vessel collapse on the mean values and phasic components of intra-myocardial flows. PMID- 2214734 TI - Pressure measurements during automatic breast compression in mammography. AB - Breast compression during X-ray mammography results in improved image quality at a lower radiation dose to the patient, and, as a consequence, the Department of Health recommends that automatic breast compression devices are fitted to mammographic X-ray units. However, the degree of breast compression is not standardized and can vary depending on the size of the patient, the particular mammography X-ray unit and the conditions of its use. A pressure measuring system was used to determine accurately the pressure on the breast. This system takes the form of a fluid-filled neonatal cuff connected to a pressure transducer by a fluid line. The pressure measuring system was calibrated and tested, first without and then with the patients, to assess its practical feasibility. The elements of the pressure measuring system, the techniques involved in its calibration and its use on patients in the clinical environment are described here. The system has proved to be a quick and simple method of relating the pressure on the breast to the pressure reading of the mammography X-ray unit. PMID- 2214735 TI - End-cap for the biomechanical testing of spinal segments. AB - Precise mechanical loading is essential in the in vitro evaluation of spinal fixation instrumentation, but the control of experimental variables is difficult because of variations in specimen morphology, size and end conditions, and gross specimen flexibility. This paper describes an end-cap which is simple in design, time efficient in its attachment to the spine and which provides precise positioning and rigid control of the end fixation points, resulting in excellent experimental control. It is easily adapted to human or animal specimens and provides a reliable load application unit, which permits specific physiological end conditions to be applied. PMID- 2214736 TI - New method for motion measurement and control. AB - A simple, inexpensive and novel method is proposed to acquire information on the motion characteristics of a patient during ambulation, by assuming the earth's magnetic field as reference. PMID- 2214737 TI - Effect of histamine antagonists on myocardial carcinine metabolism during compound 48/80-induced shock. AB - Carcinine (beta-alanylhistamine) is an imidazole dipeptide that exists in mammalian hearts, increases cardiac contractility, and is metabolically linked to carnosine (beta-alanylhistidine), a non-mast cell histidine and histamine precursor during stress. We have previously shown that tissue carnosine levels are regulated by H1 and H2 receptors. This study evaluated the effects of H1, H2, and mast cell degranulation blockers on metabolism of carcinine and related imidazoles during shock induced by compound 48/80, a mast cell degranulator. Fifty 125-g male Sprague-Dawley rats were divided into nine ip treatment groups: saline, 48/80, lodoxamide (LOD, mast cell degranulation inhibitor), diphenhydramine (DPH, H1 antagonist), cimetidine (CIM, H2 antagonist), LOD + 48/80, CIM + 48/80, DPH + 48/80, or DPH + CIM + 48/80. Heart tissue was analyzed at 30 min by HPLC. 48/80 caused decreases in myocardial carnosine (P less than 0.01) and histidine (P less than 0.0001) levels and concomitant increases in carcinine (P less than 0.01), histamine (P less than 0.01), and 3-methylhistamine (P less than 0.05) compared to those of controls. These changes were inhibited by LOD or DPH. Treatment with CIM significantly increased myocardial carcinine levels compared to 48/80 alone (P less than 0.001) without an additional effect on the other compounds. These data indicate that carcinine is involved in the cardiac response to stress via the carnosine-histidine-histamine pathway. Compound 48/80-induced shock increases histamine metabolism via this pathway resulting in mobilization of myocardial carnosine and histidine to carcinine and histamine; this effect is increased by H2 receptor blockade. PMID- 2214738 TI - Protein intake and 5-fluorouracil toxicity in tumor-bearing animals. AB - The administration of chemotherapy is limited in clinical situations by lack of selective antineoplastic activity resulting in significant host toxicity. Although it has been suggested that nutrition support can reduce chemotherapy related toxicity, few controlled studies exist to document this clinical impression. This study was performed to determine the effect of enteral protein intake on 5-fluorouracil toxicity in tumor-bearing animals. Seventy-nine female Lewis/Wistar rats with subcutaneous mammary tumor implants (AC-33) were randomized to receive either standard protein (22.0% protein; 4.27 kcal/g) or an isocaloric, protein-depleted diet (0.03% protein; 4.20 kcal/g). One-half of the animals in each group received daily injections of 5-fluorouracil (15- or 25 mg/kg ip) or placebo (saline) for 4 or 5 days. Standard protein intake significantly increased host body weight and decreased leukopenia at low (15 mg/kg) and high (25 mg/kg) 5-fluorouracil therapy. At high-dose 5-Fluorouracil (25 mg/kg), the incidence and duration of diarrhea were decreased in animals receiving standard protein intake. Thus, enteral protein intake significantly reduced clinical and objective 5-fluorouracil toxicity and improved body weight in this tumor-bearing animal model. PMID- 2214739 TI - Alpha 1-antitrypsin phenotypes in patients with abdominal aortic aneurysms. AB - The alpha 1-antitrypsin phenotypes were determined in 47 patients with abdominal aortic aneurysms. The MM phenotype was present in 85%, the MS phenotype in 4%, the MZ phenotype in 11%, and the ZZ phenotype not present in any patients. The MZ phenotype occurred significantly more often in patients with aneurysms than would be expected in the general population. The current data would support a genetic mechanism of either autosomal-dominant or multifactorial influences but not an X linked mechanism for families with a history of abdominal aortic aneurysms. PMID- 2214740 TI - The effect of intraperitoneal administration of sodium tolmetin-hyaluronic acid on the postsurgical cell infiltration in vivo. AB - Intraperitoneal administration of sodium tolmetin-hyaluronic acid reduced the formation of adhesions at early postsurgical time points. In addition, at 6, 48, 72, and 96 hr following surgery, there was a significant reduction in the number of red blood cells (RBC) recovered from peritoneal lavage. This effect was not the result of fluid or viscous solution in the peritoneal cavity since intraperitoneal administration of Ringer's lactate or Hyskon (a 32% solution of Dextran 70) did not affect RBC recovery. In contrast, the influx of leukocytes into the peritoneal cavity was elevated at 12 hr after surgery, but suppressed at 96 hr. These data may suggest a mechanism by which sodium tolmetin in hyaluronic acid reduced adhesion formation. PMID- 2214741 TI - Effect of prostaglandin E in multiple experimental models. IV. Effect on resistance to endotoxin and tumor necrosis factor shock. AB - Administration of a long-acting prostaglandin E, 16,16-dimethyl-PGE (dPGE), to rats improves their survival of bacterial peritonitis. We examined the mechanism of this protective effect with reference to its interaction with the release of cachectin (TNF). Sixty rats received saline, 20 micrograms/kg dPGE, or 80 micrograms/kg dPGE 12 hr prior to endotoxin and continuing for 48 hr. Survival rates for the saline, 20 micrograms/kg dPGE, and 80 micrograms/kg dPGE groups were 0, 40, and 85%, respectively. Forty rats received saline or 80 micrograms/kg dPGE, with the initial dose being 3 hr following endotoxin challenge and continuing for 48 hr. Survival rates for both groups were 0%. Sixty rats received saline or 80 micrograms/kg dPGE at 12 and 1 hr prior to endotoxin. Two hours after challenge, they were sacrificed and plasma TNF levels were assayed. The plasma TNF level in saline-treated rats was 22.72 +/- 0.83 ng/ml and in the dPGE treated group, 16.03 +/- 1.13 ng/ml (P less than 0.001). PMID- 2214742 TI - An improved technique for his bundle recording and ablation in dogs. AB - Many physiological investigations of cardiac function require accurate control of heart rate. To examine heart rate effects at values lower than the intrinsic heart rate requires the ability to prevent an accelerated junctional rhythm from becoming dominant even after the sinus node is eliminated. A new method for the simple and reliable production of complete atrioventricular heart block in open chest dogs is presented. It consists of two bonded parallel 22-gauge needles, one containing a bipolar recording electrode for localization at its tip and the other used for immediately adjacent formalin injection. The catheter is easily constructed, sterilizable, reusable, and durable, and can also provide a stable means of recording the His bundle electrical activity. Initial experiments performed in the first five dogs using this technique produced complete heart block with a stable ventricular escape rhythm in all five cases. PMID- 2214743 TI - Vascular response to cyclosporine and verapamil in the rat pancreas. AB - Marked elevation of vascular resistance in the rat pancreas is shown after systemic infusion of cyclosporine. Verapamil administration after cyclosporine reversed this effect and allowed maintenance of baseline vascular resistance and blood flow to the pancreas despite additional infusions of cyclosporine. Cyclosporine toxicity in rat pancreas may be directly related to increased vascular resistance. Verapamil might offer protection from this effect. PMID- 2214744 TI - Changes in mucosal nutrient transport in small and large ileal reservoirs after endorectal ileal pullthrough. AB - It has been hypothesized that, following colectomy and endorectal ileal pullthrough with ileal reservoir (PTR), reservoir tissue might lose some of its normal nutrient transport capacity and assume properties of the colon. Whether reservoir size influences the expected alterations in normal mucosal absorption and thus contributes to changes in intraluminal ecology has not previously been investigated. To study this, the everted intestinal sleeve technique was used to measure uptake of four nutrients in two groups of dogs who underwent PTR: five with a small (5 cm) lateral reservoir and five with a large (18 cm) reservoir. Mucosal samples were taken from normal ileum and colon and from reservoirs 3 months postoperation. Active uptake of carbohydrates (glucose), amino acids (proline), and bile acids (taurocholate) and passive uptake of short chain fatty acids (propionate) were markedly decreased in mucosa of both reservoir sizes compared to normal ileum (P less than 0.05, t test) and more closely approximated that of normal colon. Uptake of glucose, proline, and taurocholate in large reservoirs was significantly less than that in small reservoirs (P less than 0.05). We conclude that (1) ileal reservoir mucosa has a significantly reduced capacity for nutrient uptake, (2) ileal mucosa in small reservoirs shows higher nutrient uptake rates than mucosa in large reservoirs, and (3) short, well emptying reservoirs appear best suited to optimizing the intraluminal environment and thus enhance reservoir function when performing PTR. PMID- 2214745 TI - Lactic acidosis increases tumor necrosis factor secretion and transcription in vitro. AB - Lactic acid has been shown to affect numerous biologic processes. We investigated the role of lactic acidosis as a signal for the production of TNF by macrophages in vitro. Male F344 rats were administered thioglycolate media intraperitoneally. Macrophages were recovered 7 days later, cultured for 24 hr in complete media (CM), or CM with L-lactic acid (5, 10, or 15 mM), or with endotoxin (LPS) (10 micrograms/ml). TNF levels were measured in the supernatants. Female C57BL/6 mice were similarly treated, and macrophages were harvested and cultured in CM or CM containing lactic acid (15 mM), or LPS (10 micrograms/ml). RNA was extracted after 24 hr, separated by electrophoresis, and transferred to nitrocellulose. Human 32P-cDNA TNF and actin probes were used to determine relative TNF gene expression. Gel densitometry was used to calculate the TNF expression index (EI) in lactic acid and LPS treated cells as described. pH levels of the supernatant indicated that increasing concentrations of lactic acid caused increasing acidosis. Trypan blue exclusion demonstrated that lactic acidosis did not reduce cell viability. LPS significantly increased secretion of TNF relative to control (P less than 0.001). Each concentration of lactic acid significantly increased TNF secretion (P less than 0.05), but not in a dose-dependent manner. TNF gene transcription was elevated in macrophages cultured with lactic acid and LPS relative to control (EI = 1.13 and 1.18, respectively). This suggests that lactic acid concentration can regulate TNF secretion at the level of transcription, and is consistent with the hypothesis that local levels of lactic acid (lactic acidosis) may be a regulator of cytokine secretion. PMID- 2214746 TI - Hemodynamic effects of glucagon after acute mesenteric ischemia in rats. AB - We have previously shown that iv glucagon improved survival in rats from 33 to 83% when given after, but not during, superior mesenteric artery (SMA) occlusion. This study investigated potential hemodynamic mechanisms of this effect. In Part 1, cardiac output (CO) was measured in 12 male Sprague-Dawley rats with an electromagnetic flow-probe that had been placed around the ascending aorta 5 days previously. Under pentobarbital anesthesia, the SMA was occluded for 85 min. All rats received normal saline (NS, 15 ml/kg/hr) for 1 hr before and after SMA declamping. Control rats (n = 6) received only NS. Treated rats (n = 6) received NS plus glucagon (1.6 micrograms/kg/min iv) for 1 hr postocclusion. CO decreased 50% during the first hour after SMA declamping in control rats, but only 11% in glucagon-treated rats (P less than 0.02). Systemic vascular resistance (SVR) increased by 90% in control rats by 1 hr after declamp, but only 9% in glucagon rats (P less than 0.04). Systemic blood pressure and heart rate were not different in the two groups. In Part 2, relative distribution of visceral blood flow was measured with radiolabeled microspheres injected in the aortic root before clamping, before declamping, and 1 hr postdeclamping in 10 rats (5 glucagon, 5 control) using the above protocol. After SMA clamping, the proportion of visceral blood flow distributed to the intestine fell from 45 to 20% (P less than 0.05). During reperfusion, the proportion of intestinal flow exceeded baseline (P less than 0.05), but was not different in control (64%) and glucagon treated rats (56%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214747 TI - Radical splenopancreatectomy with duodenal loop conservation in rats. AB - In an attempt to find a reproducible method of total splenopancreatectomy (TSP) with duodenal loop conservation in rats, we used the technique recently described by S. Houry and M. Huguier (Eur. Surg. Res. 15: 328, 1983) but were not able to induce a true diabetes. We therefore developed a more radical splenopancreatectomy (RSP) in rats and compared this technique with the TSP. RSP involves a more extensive dissection of the common bile duct, a short choledocoduodenal anastomosis, and total excision of the retroportal pancreatic lobules with the aid of a dissecting microscope. In rats who had undergone the TSP technique, blood glucose levels were maximal 8 hr after operation (270 +/- 16 mg/dl), and thereafter recovered baseline values. In contrast, after the RSP technique all the rats became diabetic as documented by persistent hyperglycemia (347 +/- 20 mg/dl at 8 hr, P = 0.01 compared to TSP; 500 +/- 20 mg/dl at 8 hr, P less than 0.0001). Eight hours after the operation, blood lipase levels increased more significantly after TSP than after RSP (847 +/- 247 IU/liter and 130 +/- 37 IU/liter, respectively, P = 0.01), and then decreased to 92 +/- 19 IU/liter at 24 hr in the TSP group and less than or equal to 30 IU/liter in the RSP group (P = 0.003), suggesting a more radical dissection of pancreatic tissue with the RSP technique. At sacrifice at 48 hr, no complications were found with either technique on macroscopic and microscopic examination, except for marked gastric distension with RSP. A third group of rats underwent RSP and were followed until natural death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214748 TI - En bloc simultaneous pancreas and kidney allotransplantation in the pig. AB - The pig is a large animal suitable for experimental pancreas transplantation due to its anatomy and transplant immunology, both of which are similar to humans. We established a model of en bloc simultaneous pancreas and kidney transplantation that decreases preservation time, operation time, and clamp time. The donor aorta -with celiac axis, superior mesenteric artery, and left renal artery--is anastomosed en bloc to the recipient's aorta in a side-to-oblique fashion. The portal vein is anastomosed end-to-side to the distal vena cava, and the left renal vein end-to-side to the left common iliac vein. The donor duodenum is anastomosed to the bladder to allow monitoring of the urinary amylase for rejection. En bloc transplantation is preferable for separating pancreas and kidney anastomoses in pigs. This technique could be used in humans, especially in adult uremic diabetic patients who receive a combined pancreas/kidney transplant from a pediatric cadaver donor. PMID- 2214749 TI - Veneered osseous graft. Case report and technique. AB - Attempts to develop a predictable method of osseous regeneration evolved into the veneered osseous graft. The author has taken advantage of and incorporated several different aspects of regenerative periodontal therapy. Having treated several hundred cases with good to excellent results, success is directly related to meticulous detail. Flap design, root surface preparation, bony wall therapy and graft placement are all equally important in predicting success. By introducing into a clean bone cavity against a clean root an osteogenic base material protected by a veneer to prevent down growth of epithelium one can expect improvement of an osseous lesion. This one-step procedure is a cost effective answer to the two-step procedure. Osseous grafting with a variety of materials has become an established part of regenerative periodontal therapy. Most reports comparing grafting to surgical debridement has demonstrated an advantage with grafting no matter what the material. Successful osseous grafting does require a biologically compatible material, preferably with osteogenic potential, which would prevent a down growth of epithelium until the graft has established a "home." Equally important is site preparation. Most reports in the literature describe site preparation as "thorough root planing." This description is inadequate as actual procedures can vary widely. Specifics are missing so duplication is difficult. Chemical root conditioning was introduced as an adjunct to effective root preparation. The frequency of osseous graft success began to improve with the addition of citric acid conditioning to very mechanical root preparation regardless of the grafting material used. The development of the veneered osseous graft technique over the years has taken advantage of and incorporated several different aspects of regenerative therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214750 TI - AV nodal reentrant tachycardia. AB - During the past decade, the mechanisms of SVT have been discovered by intracardiac electrophysiologic studies. The differentiation of the various forms of tachycardia allows a more rational approach to therapy. Bedside maneuvers and the 12-lead ECG will identify the correct mechanism of SVT in the majority of patients. Diagnostic clues from the surface ECG include the position and morphology of the P wave, heart rate, change in rate with bundle-branch block, presence of AV block, and the initiation and termination of the SVT. With the use of bedside maneuvers and clues from the surface ECG, an intracardiac electrophysiologic study would be indicated only for recurrent SVT that is refractory to medical therapy and is potentially life-threatening. PMID- 2214751 TI - Infant botulism in Tennessee. PMID- 2214752 TI - A brief history of pneumonia. PMID- 2214753 TI - Blunt intestinal trauma. PMID- 2214754 TI - A case of headache and amnesia. PMID- 2214755 TI - Hypokalemia and weight loss in a young woman. PMID- 2214756 TI - Blacks and high blood pressure. PMID- 2214757 TI - The loser finally wins. PMID- 2214758 TI - Antiandrogen ICI 176,334 does not prevent development of androgen insensitivity in S115 mouse mammary tumour cells. AB - Many forms of endocrine therapy for steroid-sensitive tumours involve regimes of steroid agonist deprivation by administration of steroid antagonists. The partial or short-lived response to such therapy results from the inevitable progression of the tumour cells to a state of steroid insensitivity. Several cell culture systems have shown that steroid ablation results in loss of steroid sensitivity and we have used an in vitro model here to study the influence of steroid antagonists on this progression. Growth of androgen-responsive S115 mouse mammary tumour cells in the long-term absence of steroid results in a loss of androgen sensitivity. We have studied here the effects of the pure antiandrogen ICI 176,334 on the growth of S115 cells and on their progression to steroid autonomy. Although a pure antiandrogen in its action on these cells with very low toxicity, it had no protective effect against loss of cellular or molecular androgen responsive parameters. The clinical implications for endocrine therapy are discussed. PMID- 2214759 TI - Hydroxylated triphenylacrylonitriles adopt a unique orientation within the binding site of the estrogen receptor. AB - The relative binding affinities of a series of twelve para-hydroxylated triphenylethylenes (TPEs) for the estradiol receptor (ER) of calf uterus cytosol were measured by a competition method. The results obtained under equilibrium conditions support the hypothesis of the additivity of the energies corresponding to each of the hydrogen-bond type interactions of di- or tri-hydroxylated TPEs with the estradiol binding site of ER and strongly suggest that, whichever ring is hydroxylated, the orientation of the TPE in the steroid binding site is always the same. A hydroxyl group in a given position always interacts with the same location within the site. Mono-hydroxylation of the highly hydrophobic non substituted TPE skeleton led to a large increase in relative binding affinity for ER which could be explained by a dual mechanism whereby the interaction specific to the hydroxyl is accompanied by a temperature- or time-dependent binding process that is not related to the hydroxylation position. PMID- 2214760 TI - Methandrostenolone metabolism in humans: potential problems associated with isolation and identification of metabolites. AB - Methandrostenolone dose (amount and duration) and methods of isolation from urine can influence the identification and quantitation of methandrostenolone metabolites. Long-term use of methandrostenolone at high dosages led to the appearance of unmetabolized drug in the urine and contributed to the identification of a previously unreported metabolite, 3 beta, 6 section, 17 beta trihydroxy-17 alpha-methyl-5 section-1-androstene. Exposure of methandrostenolone in vitro to acid conditions induced a retropinacol rearrangement in the D-ring of the methandrostenolone molecule, causing the formation of 18-nor-17,17-dimethyl 1,4,13(14)-androstatrien-3-one in large amounts. The same acidic conditions led to the addition of a hydroxyl at the 6 position of the B-ring of either the retropinacol rearrangement products or native methandrostenolone resulting in the formation of 6 beta-hydroxy-18-nor-17,17-dimethyl-1,4,13(14)-androstatrien-3-one, 6 alpha- hydroxy-18-nor-17,17-dimethyl-1,4,13(14)-androstatrien, 6 beta-17 alpha methyl-1,4-androstadien-3-one and 6 alpha,17 beta-dihydroxy-17 alpha-methyl-1,4 androstadien-3-one. Hydroxylation of native methandrostenolone at the 6 position also occurs endogenously. However, no evidence of an endogenous retropinacol rearrangement was found. Silylating agents alone can induce the formation of small amounts of 6 beta-17 beta-dihydroxy-17 alpha-methyl-1,4-androstadien-3-one. Discrepancies between previously published reports on methandrostenolone metabolism in man are discussed and compared with an animal model. PMID- 2214761 TI - Specific nuclear uptake of intracellularly-produced estrogen by rat granulosa cells. AB - Granulosa cells of the ovarian follicle are unique in that they both synthesize steroid hormones and respond to exogenously-administered steroids. Isolated granulosa cells from ovaries of gonadotropin-primed rats were incubated in the presence of [3H]testosterone, which the cells convert to [3H]estradiol. Nuclear extracts of these cells were analyzed by high-performance liquid chromatography in a system of 40% acetonitrile. When cells were incubated in the presence of [3H]testosterone alone, a significant portion of the radioactivity present in nuclei co-eluted with authentic estradiol. The nuclear binding was considered to be specific, since 50-75% of total binding was suppressed when the incubation medium contained excess unlabeled estrogen. Moreover, when an antibody to estradiol was included in the medium, specific nuclear uptake of [3H]estradiol was not abolished, but rather was increased. Granulosa cells may, therefore, directly utilize endogenously-produced estradiol, a mechanism which may play a role in the regulation of ovarian cells. PMID- 2214762 TI - Modulatory actions of the new antiprogestins ZK 98.299 and ZK 98.734 and of RU 486 on luteinizing hormone secretion and progesterone effects in pituitary gonadotrophs. AB - The effects of the antiprogestins (APs) ZK 98.299, ZK 98.734 and RU 486 on GnRH stimulated LH secretion and their antagonistic activity on progesterone (P) actions were investigated in cultured pituitary cells from adult female Wistar rats. P (100 nM) was able to exert a facilitatory effect on GnRH (1 nM)-induced LH secretion after short-term (4 h) treatment of estradiol-primed (1 nM, 48 h) rat pituitary cells. When the APs (10 pM-10 microM) were introduced during the 4 h incubation period with P the facilitatory effect of P was totally abolished at concentrations greater than 10 nM (ZK 98.299, ZK 98.734) and greater than 1 nM (RU 486). Also the APs were shown to block the inhibitory action of P which occurs after long-term incubation of pituitary cells with this steroid. However at concentrations greater than 10 nM (ZK 98.734, RU 486) and greater than 100 nM (ZK 98.299) this antagonistic action of the APs was lost. To evaluate whether the APs have direct effects on GnRH-induced LH secretion in the absence of exogenous P pituitary cells cultivated for 48 h with or without 1 nM estradiol were incubated for 4 or 24 h with increasing concentrations of the APs (10 pM-10 microM). Four hour treatment of non-estradiol-primed cells with ZK 98.299 or ZK 98.734 was without any effect on the LH response to a 1 nM GnRH-stimulus. Only the highest concentration of RU 486 (10 microM) reduced the LH response. Twenty four hour treatment of the cultures with the APs led to enhancement of GnRH stimulated LH secretion by up to 113, 37 and 33% for ZK 98.734, ZK 98.299 and RU 486, respectively. When estradiol-primed cells were used for the same experiments we observed exclusively inhibitory effects on GnRH-induced LH secretion after 4 and 24 h treatment periods. It is concluded that these new APs are potent inhibitors of P-actions, but also per se they induce diverse effects on GnRH stimulated LH secretion in cultured rat pituitary cells which have to be taken into account. PMID- 2214763 TI - Progestin binds to the glucocorticoid receptor and mediates antiglucocorticoid effect in rat adipose precursor cells. AB - The binding of progestin and glucocorticoid hormones was examined in the cytosol of rat adipose precursor cells. Progestin binding sites of high affinity and limited capacity were present in the cytosol of adipose precursor cells from female rats, but not from male rats, by using [3H]R5020 as radioligand. Glucocorticoid binding sites of high affinity and limited capacity were present in the cytosol of these cells from both male and female rats by using [3H]dexamethasone and [3H]triamcinolone acetonide as radioligands. The dissociation constants were in the physiological concentration range. Studies of competitive binding showed that progestin could compete with glucocorticoids at glucocorticoid binding sites. In a serum free medium glucocorticoid effect on cellular differentiation, monitored by glycerophosphate dehydrogenase (GPDH), was effectively counteracted by progesterone which by itself had no effect. These results demonstrate that progestin receptor exists only in rat adipose precursor cells from female rats, while glucocorticoid receptor exists in rat adipose precursor cells of both sexes. Glucocorticoid effects on cellular differentiation in these cells are mediated by the glucocorticoid receptor. Progestin binds to the glucocorticoid receptor and antagonizes glucocorticoid effect on cellular differentiation in these cells. PMID- 2214764 TI - Luteolytic effect of the antiprogestin and antiglucocorticoid agent RU486 in rats. AB - Ovarian cells of pregnant rats were cultured with synthetic progestins (R5020, R2323), dexamethasone and RU486. Progesterone and 20 alpha-hydroxy-pregn-4-en-3 one (20 alpha-dihydroprogesterone) in the medium were measured by specific radioimmunoassay. Both R5020 and R2323 increased concentrations of these intrinsic progestins. RU486 decreased concentrations of progesterone, however, the addition of R5020 or R2323 counteracted this action. Immature hypophysectomized rats treated with pregnant mare serum gonadotropin (PMS) and human chorionic gonadotropin (hCG) were administered with RU486; the serum levels of progesterone and 20 alpha-dihydroprogesterone tended to decrease. R5020 and R2323 inhibited the effect of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), whereas RU486 did not. Inhibition of the cholesterol side chain cleavage enzyme (CSCC) by RU486 was more marked than that by R5020 or R2323. These results show that RU486 decreases progesterone synthesis in cultured ovarian cells. A part of the mechanism may involve an inhibition of CSCC. PMID- 2214765 TI - A novel lanosterol isomer produced in response to azole antifungals. AB - Gas chromatography-mass spectrometry has revealed the existence of a novel lanosterol-like sterol which is produced by fungi in response to treatment with azole drugs. The significance of this finding may be related to the changes in fungal sterol synthesis as a consequence to prolonged exposure to azoles and consequent development of resistance to these agents. PMID- 2214766 TI - Differences in the form of the salt-transformed estrogen receptor when bound by estrogen versus antiestrogen. AB - Our laboratory has previously reported that antiestrogen binding to molybdate stabilized non-transformed estrogen receptor results in a larger form of the receptor in 0.3 M KCl when compared with estrogen bound receptor. Estradiol promoted the formation of monomers in the presence of 0.3 M KCl whereas antiestrogen appeared to promote dimer formation. We have extended these studies examining the rabbit uterine salt-transformed estrogen receptor partially purified by DEAE-cellulose chromatography. We previously demonstrated that estrogen receptor prepared in this way bound to different sites on partially deproteinized chromatin subfractions or reconstituted chromosomal protein/DNA fractions when the receptor was complexed with estrogen vs antiestrogen. Analysis of these receptor preparations indicated that DEAE-cellulose step-elution resulted in a peak fraction which sedimented as a single 5.9S peak in 5-20% sucrose density gradients containing 0.3 M KCl for receptor bound by the antiestrogens H1285 and trans-hydroxytamoxifen. However, receptor bound by estradiol sedimented as 4.5S. These receptor complexes bound DNA-cellulose indicating that these partially purified receptors were transformed. DEAE rechromatography or agarose gel filtration of the partially purified antiestrogen receptor complexes resulted in significant dissociation of the larger complex into monomers. Incubations of 5.9S antiestrogen-receptor complexes with antibodies against nontransformed steroid receptor-associated proteins (the 59 and 90 kDa proteins) did not result in the interaction of this larger antiestrogen-receptor complex with these antibodies (obtained from L. E. Faber and D. O. Toft, respectively). Our results support the concept that antiestrogen binding induces a different receptor conformation which could affect monomer dimer equilibrium, thus rendering the antiestrogen-receptor complex incapable of inducing complete estrogenic responses in target tissues. PMID- 2214767 TI - Inhibitory effect of a new androstenedione derivative, 14 alpha-hydroxy-4 androstene-3,6,17-trione (14 alpha-OHAT) on aromatase activity of human uterine tumors. AB - The development of human uterine estrogen-dependent tumors is considered to be closely related to estrogen biosynthesis. This study examined whether or not 14 alpha-hydroxy-4-androstene-3,6,17-trione (14 alpha-OHAT), a new 4-androstene-3, 17-dione derivative synthesized microbiologically, inhibits estrogen biosynthetase (aromatase) activities of human uterine tumors (i.e. uterine endometrial cancer, uterine leiomyoma and uterine adenomyosis tissues). 14 alpha OHAT inhibited aromatase activity in all uterine tumors, dose-dependently (0.1-10 microM). Moreover, 14 alpha-OHAT did not show the binding affinity to rabbit uterine cytosol-sex steroids, and it was not converted to estrogen in human placental preparations. Thus, 14 alpha-OHAT, an aromatase inhibitor, may be useful clinically as an endocrine chemotherapy for peri- or post-menopausal women with uterine estrogen-dependent tumors. PMID- 2214768 TI - Ovarian function in premenopausal women affected by breast cancer: the measurement of glucuronoconjugate metabolites of 17 beta-estradiol and progesterone throughout one entire menstrual cycle. AB - For many years, hypersecretion of estrogens has been suspected of being one of the major risk factors of breast cancer for premenopausal women. Seventeen premenopausal women, who had undergone lumpectomy because of breast cancer (T1a No Mo) 3 yr before entering the study, were compared to 9 normal women of similar age, parity and body weight. A chemiluminescent method was used for the determination of estrone-3-glucuronide (E1-3G) and pregnanediol-3-glucuronide (Pd 3G) in early morning urine samples collected for an entire menstrual cycle of each of the 26 subjects. During the follicular phase, no significant differences in E1-3G and/or Pd-3G excretion were found between the two groups. During the luteal phase the E1-3G/Pd-3G ratio in the early, middle and late luteal phase had significantly increased in the women with breast cancer, in spite of normal Pd-3G excretion. Therefore, the measurement of glucuronoconjugate metabolites of ovarian hormones in overnight urine might be conveniently applied to the study of ovarian function in subjects with breast cancer. Furthermore, the results of this study may indicate that an estrogen/progesterone imbalance is an additional risk factor for the premenopausal breast cancer patient. PMID- 2214769 TI - In vitro synthesis of 16 alpha-hydroxyestrone by female rat liver microsomes: its possible role in the etiology of breast cancer. AB - Liver homogenates from female rat strains (Sprague-Dawley, Wistar and Fisher) were incubated in a NADPH regenerating medium in the presence of labelled and unlabelled estrone. Liver microsomes isolated from male rats and female mice were used as positive controls. Using HPLC and paper chromatography, under the experimental conditions used it was found that liver homogenates from female rats were able to convert estrone to various metabolites such as 16 alpha hydroxyestrone. In a mutagenicity assay (Ames test), with 16 alpha hydroxyesterone as test substance, two strains (TA98 and TA1538) of the five strains tested showed a 2-3-fold increase in the number of his+ revertants relative to the control values. Estrone did not cause any mutagens in the test used. It is concluded that female rats are able to synthesize 16 alpha hydroxyestron in vitro. Whether this compound is risk factor for breast cancer remains unclear. PMID- 2214770 TI - 7-substituted 1,4,6-androstatriene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase. AB - 7-Phenyl-1,4,6-androstatriene-3,17-dione (4), 7-benzyl-1,4,6-androstatriene-3,17 dione (5) and 7-phenethyl-1,4,6-androstatriene-3,17-dione (6) were synthesized and evaluated in vitro in human placental microsomes as enzyme-activated irreversible inhibitors of aromatase. The compounds were synthesized from appropriate 7-substituted 4,6-androstadiene-3,17-diones by reaction with DDQ under neutral conditions. All the compounds produced a first order inactivation of aromatase in the presence of NADPH but not in the absence of NADPH. Substrate 4-androstene-3,17-dione protected the enzyme from inactivation by the inhibitors. Furthermore, cysteine failed to protect aromatase from inactivation by compounds 5 and 6. In contrast, cysteine partially protected aromatase from inactivation by compound 4. Irreversibility studies illustrated the covalent nature of the inactivation by 4, 5 and 6. The above experimental evidence demonstrated that compounds 5 and 6 are effective enzyme-activated irreversible inhibitors of aromatase. PMID- 2214771 TI - Genetic polymorphism of the human sex hormone-binding globulin: evidence of an isoelectric focusing variant with normal androgen-binding affinities. AB - Human sex hormone-binding globulin (hSHBG) is a plasma glycoprotein composed of two identical subunits. The protein, which has high affinity for testosterone and estradiol has been purified to homogeneity. In this study we have investigated, on neuraminidase-treated serum samples, the presence of genetic variations of hSHBG by polyacrylamide gel isoelectric focusing (IEF). Based on IEF analyses of 110 serum samples from adult Mexican individuals we have identified two distinct IEF-patterns. The most frequent phenotype (95.45%) was characterized by two IEF bands with pIs of 6.50 and 6.63, respectively. In five serum samples, a different 4-band pattern with pIs of 6.50, 6.63, 6.70 and 6.76 was identified. Family studies showed that this pattern was genetically determined. The frequency of this variant was 4.55%, and the observed phenotypes were consistent with the expression of an autosomal genetic system. The estimated gene frequencies for both alleles were shown to be in genetic equilibrium. Affinity constants, binding kinetics and serum concentrations of hSHBG from individuals having a 4-band pattern were similar to those obtained in individuals with a 2-band pattern, thus suggesting that the mechanism responsible for the generation of polymorphic variants of hSHBG reported herein did not involve the steroid binding site of the molecule. These findings may be of broad interest, as other serum binding proteins express genetic variants, which may permit their further structural and functional subclassification. PMID- 2214772 TI - A comparative study of the selectivity and efficiency of target tissue uptake of five tritium-labeled androgens in the rat. AB - A comparative study of the tissue distribution of five tritium-labeled androgens was done in rats to determine the efficiency and selectivity of their uptake by target tissue. Testosterone (T), 5 alpha-dihydrotestosterone (DHT), 19 nortestosterone (nor-T), mibolerone (Mib) and methyltrienolone (R1881) all showed selective uptake by the ventral prostate in one-day castrated rats (250 g) that was 61-90% displaceable by co-injection of an excess of unlabeled steroid. The greatest uptake was with R1881 (0.69% injected dose per gram prostate tissue (%ID/g) at 1 h), and Mib (0.56% ID/g); the other three showed lower uptake (approx. 0.4% ID/g). The target tissue activity remained high for all compounds up to 4 h after injection, and at 2-4 h the prostate to blood ratio for Mib and R1881 exceeded 10 and 20, respectively. The uptake efficiency and selectivity of these five androgens appear to be related to their affinity for the androgen receptor and their resistance to metabolism. Mib and R1881 have substantial affinity for other steroid receptors, which might account for some of their prostate uptake. However, co-administration of triamcinolone acetonide, which has high affinity for progesterone and corticosteroid receptors but not for the androgen receptor, failed to block their uptake significantly, whereas co administration of DHT, the most selective ligand for the androgen receptor, blocked their uptake as completely as the unlabeled tracer itself. The prostate uptake of Mib and R1881 in intact animals was significantly lower than in castrated animals, but treatment of the intact animals with diethylstilbestrol restored their uptake nearly to the level seen in castrated animals. These uptake patterns are consistent with earlier studies of in vivo androgen uptake and with known changes in androgen receptor content and occupancy as a result of castration or diethylstilbestrol treatment. They further suggest that high affinity androgens labeled with suitable radionuclides--particularly derivatives of mibolerone (Mib) or methyltrienolone (R1881)--may be effective receptor-based imaging agents for androgen target tissues and tumors, even when patients are already receiving hormonal therapy. PMID- 2214773 TI - Selective inhibition of cytochrome P-450 in rat testicular microsomes: effect of cobalt-protoporphyrin on progesterone metabolism. AB - Cobalt-protoporphyrin (CoPP) administration to adult male rats results in a profound reduction in hepatic cytochrome P-450 concentration and activity, and decreased plasma concentrations of testosterone and luteinizing hormone (LH). The metabolism of progesterone by rat testicular microsomes isolated 48 h after treatment in vivo with CoPP was compared to that in microsomes from control rats. The conversion of progesterone to 17 alpha-hydroxyprogesterone and 4 androstenedione, which is NADPH-dependent, was reduced by approximately 40% in testicular microsomes following treatment with CoPP (50 mumol/kg body weight) and this inhibition was dose-dependent. The concentration of cytochrome P-450 in testicular microsomes and the activity of 7-ethoxycoumarin de-ethylase (a cytochrome P-450 dependent function) were also reduced following treatment with CoPP in contrast to two other functional assays of cytochrome P-450, aryl hydrocarbon hydroxylase and ethylmorphine demethylase, which were unaffected by treatment with CoPP. Thus, the profound effect of CoPP on androgen homeostasis has been extended to include decreased testicular synthesis of 4-androstenedione in addition to increased hepatic metabolism of testosterone, attenuated pituitary LH release in response to luteinizing hormone-releasing hormone, and failure of testicular response to LH. PMID- 2214774 TI - 17 Beta-hydroxysteroid oxidoreductase activity: age-dependent profile in rat liver and kinetic properties of the hepatic microsomal enzyme in relation to cytochrome P450-dependent steroid hydroxylation. AB - The functional relationship between the microsomal cytochrome P450 and 17 beta hydroxysteroid oxidoreductase (HSOR) enzymes involved in steroid metabolism was investigated in rat liver. In male and female rat hepatic microsomes the NADPH dependent conversion of androstenedione (AD) to testosterone (T) was approx. 4 fold greater at 6 weeks of age than in 1 week old animals. In hepatic microsomes from 15 week old rats the activity of the HSOR pathway was greater in males than in females (1.51 compared to 0.80 nmol T formed/min/mg protein). However, oestradiol administration to intact adult male rats did not decrease HSOR activity. Thus, androgen is not essential for maintenance of HSOR enzymes. Instead, it is likely that irreversible androgen imprinting of the HSOR enzyme occurs during the prepubertal period. The in vitro characteristics of HSOR activity were also assessed. The Km for NADH-dependent reduction of AD to T was 9.2 microM and the Vmax was 3.0 nmol/min/mg protein but the NAD-mediated formation of AD from T did not follow Michaelis-Menton kinetics. pH markedly influenced HSOR-mediated AD/T interconversion with 17-ketosteroid reduction facilitated at low pH, and 17 beta-hydroxysteroid dehydrogenation about 2-fold more efficient at pH 8.0 than at pH 5.5. Product steroid activation of HSOR activity was noted. 17 beta-Hydroxysteroids, including T and oestradiol, activated the rate of conversion of AD to T and 17-ketosteroids such as oestrone and AD activated the NAD-dependent dehydrogenation of T. Activation was not observed at low steroid substrate concentrations so that it was not possible to analyse this phenomenon by a conventional kinetic approach. PMID- 2214775 TI - Regulation of plasma corticosteroid-binding globulin in adult cynomolgus monkey (Macaca fascicularis) during different reproductive states. AB - The plasma concentration of the corticosteroid-binding globulin (mCBG) has been measured in Macaca fascicularis, during different stages of reproduction and under hormonal treatments. The mCBG level was determined by a specific electroimmunoassay. There was no difference between females in the follicular phase and intact males; mCBG concentrations were respectively (mean +/- SEM) 469 +/- 53 and 443 +/- 25.6 nmol/l. The mCBG levels levels were similar during both the luteal (469 +/- 33.5 nmol/l) and the follicular phase (469 +/- 53 nmol/l). Compared to intact males, the mCBG levels were higher (P less than 0.05) in castrated males (527 +/- 6.6 nmol/l). During gestation, no systematic variations were found and the mCBG levels were not statistically different from the values found during the follicular phase. When estradiol benzoate was administered to castrated animals, the mCBG concentrations increased rapidly. In contrast, the values were reduced slightly by testosterone treatment. The sex-steroid action on the mCBG levels was discussed and compared with the mSBP levels. We question also, the mechanisms involved in the regulation of the mCBG levels during pregnancy. PMID- 2214776 TI - Greater conversion of testosterone to 5 alpha-dihydrotestosterone, reflecting increased peripheral 5 alpha-reductase activity in nude mice treated with high doses of cyclosporine A. AB - Following cyclosporine A (CsA) immunosuppressive therapy in kidney grafts, increased body hair growth (hypertrichosis and/or hirsutism) without significant variation in normal circulating plasma androgen levels (as observed in idiopathic hirsutism) has been reported by several authors. Other authors have described increased hair growth in nude mice treated with CsA. In order to evaluate the action of this drug in target tissues, using dorsal skin homogenates from nude mice treated with various doses of CsA, we measured the metabolic conversion of testosterone (T) to its 5 alpha-reduced products, reflecting 5 alpha-reductase activity (5 alpha-RA). Three groups of 5 female nude mice were treated with an oral suspension containing CsA 5 mg/kg (group 1), 25 mg/kg (group 2) and 100 mg/kg (group 3), respectively, and the results, including 5 alpha-DHT and Adiol formation, were compared with those obtained in a control group (n = 5) receiving only the olive oil vehicle. Cutaneous metabolic conversion of T was determined using tritiated T as substrate. After 1 h of incubation, 5 alpha-DHT and other 5 alpha-reduced products formed were separated and quantified using a reverse-phase chromatography column fitted to a flow-through radioactivity detector. Mean +/- SD 5 alpha-DHT formation (expressed as pmol per 100 mg of protein per h) was found to be increased in the treated groups (group 1: 3.17 +/- 0.37, group 2: 3.10 +/- 0.13, group 3: 4.26 +/- 0.20), respectively 7.5% (NS), 5.10% (NS) and 44.4% (P = 0.01) higher than in the control group (2.95 +/- 0.13). In addition to 5 alpha-DHT, enhanced formation of delta 4-androstenedione (delta 4), 5 alpha androstan-3 beta,17 beta-diol (3 beta-diol) and 5 alpha-androstan-3 alpha,17 beta diol (3 alpha-diol) were also observed in the treated groups. These results show a significantly increased formation of 5 alpha-DHT (and Adiol) in nude mice treated with high dose-levels of CsA. PMID- 2214777 TI - Ethanol-induced inhibition of testosterone biosynthesis in rat Leydig cells: central role of mitochondrial NADH redox state. AB - The mechanisms by which ethanol (EtOH) inhibits the human chorionic gonadotropin (hCG)-stimulated testosterone synthesis was studied in isolated rat Leydig cells in vitro. EtOH inhibited steroidogenesis, but this inhibition was reversed by L glutamate (Glu) and an uncoupler of the oxidative phosphorylation, 2,4 dinitrophenol (DNP). The mechanism of EtOH-induced inhibition was studied by measuring steroidogenic precursors and comparing them with the cytosolic and mitochondrial NADH redox states during uncoupling or in the presence of Glu. DNP had a dual effect. Low concentrations abolished the EtOH-induced inhibition of progesterone to testosterone formation suggesting that the inhibitory step was at or before progesterone formation. A large concentration led to an overall decrease in steroidogenesis indicating toxic effects on steroidogenesis. The mitochondrial NADH/NAD+ ratio, measured as the 3-hydroxybutyrate/acetoacetate ratio, decreased simultaneously when steroidogenesis was stimulated, either during uncoupling or in the presence of Glu, whereas cytosolic NADH/NAD+ ratio, measured as lactate/pyruvate ratio showed no response. These results demonstrate that the rise in the mitochondrial NADH/NAD+ ratio rather than in the cytosolic one is connected with the inhibition of testosterone synthesis by EtOH in isolated Leydig cells. The EtOH-induced high mitochondrial NADH/NAD+ ratio may deplete mitochondrial oxalacetate concentrations. This can decrease the activity of several transport shuttles and interrupt the flow of mitochondrial citrate into the smooth endoplasmic reticulum, which then reflects to decreased rate of steroidogenesis in the presence of ethanol. PMID- 2214778 TI - Estrophilic 3 alpha,3 beta,17 beta,20 alpha-hydroxysteroid dehydrogenase from rabbit liver--I. Isolation and purification. AB - A procedure for isolation of a highly-purified estrophilic hydroxysteroid dehydrogenase (EHSD) from rabbit liver, including ammonium sulphate fractionation, gel filtration, ion-exchange and affinity chromatography on estradiol-Sepharose, has been developed. The enzyme possesses NADP-dependent 3 alpha,3 beta,17 beta,20 alpha-HSD activities with a wide spectrum of androgenic, progestagenic, and estrogenic substrates. EHSD is a monomeric protein whose molecular mass determined by different methods is 35,000-39,000. The protein exhibits microheterogeneity due to the differences in molecular surface charge. The catalytic and hormone-binding properties and molecular sizes of the two protein fractions obtained by chromatography on DEAE-Toyopearl are close or identical. The enzymatic activity of EHSD is minor as compared to other HSDs from rabbit liver. However, the low values of Km, the high affinity for steroid ligands, and high tissue levels of EHSD suggest the protein to play a role in the biodynamics of sex hormones. PMID- 2214779 TI - Estrophilic 3 alpha,3 beta,17 beta,20 alpha-hydroxysteroid dehydrogenase from rabbit liver--II. Mechanisms of enzyme-steroid interaction. AB - Binding of [3H]estradiol, [3H]testosterone and [3H]progesterone to purified NADP dependent estrophilic 3 alpha,3 beta,17 beta,20 alpha-hydroxysteroid dehydrogenase (EHSD) from rabbit liver cytosol has been examined. The three steroids bind to the enzyme with moderate [corrected] affinity (Ka congruent to 10(7) [corrected] M-1 at 4 degrees C) and equal binding capacity. High-rates were shown for both association and dissociation processes. The steroids competitively inhibited the binding of each other to EHSD. At the same time, their relative binding affinities (RBA) were dependent on the nature of [3H]ligand. The results of RBA determinations for 72 steroids and their analogues by inhibition of [3H]progesterone binding to EHSD suggest that androgens and gestagens bind preferentially to the same site on EHSD molecule, while estrogens (at least by their D-ring) bind to another site. The assumption that EHSD molecule has more than one binding site for steroids is corroborated by (i) substrate inhibition revealed for a number of steroids; (ii) the estrogen ability to potentiate 20 alpha-reduction of progesterone; (iii) stimulatory effect of 5 alpha (beta) androstane-3 alpha (beta), 17 beta-diols on [3H]testosterone and progesterone binding; and (iv) reciprocal effect of NADP on [3H]estradiol and [3H]testosterone binding to EHSD. Significant differences in sensitivity to pH and changes in NaCl concentration upon metabolism and binding of various steroids have been found. At concentrations of 16 mM dithiothreitol potentiated catalytic conversion of some steroids and had no effect on metabolism of others. Both the affinity for steroids and binding capacity of EHSD are found to be cofactor-dependent. It is speculated that EHSD has a complex active center including at least two mutually influencing steroid-binding sites tightly related with cofactor-binding site. The polyfunctionality of EHSD may be due to both the excess of functional protein groups that form individual constellations upon binding of any steroid and also to conformational lability of EHSD molecule implying alternative orientations of steroids at the binding site. PMID- 2214781 TI - Serum cortisol in adrenal hirsutism as estimated by five different methods. AB - Serum cortisol had been estimated in 152 hirsute women complaining of fertility problems, of whom 36 were subsequently diagnosed as having adrenal hirsutism and 10 as having congenital adrenal hyperplasia (steroid 21-hydroxylase deficiency), using five methods: an in-house tritium radioimmunoassay after extraction with ethanol; the Diagnostic Products Corp. "Coat-a-count" iodinated direct radioimmunoassay; the Pharmacia-LKB "DELFIA" lanthanum-enhanced fluoroimmunoassay; the Amersham "Amerlite" luminescence immunoassay; and the Walker "Synelisa" enzyme-linked immunoassay. Although stripped pool serum samples containing weighed amounts of cortisol produced acceptable values in all assays, the patient samples showed a number of high results, much greater than the accepted normal upper limit of 250 ng/ml (25 micrograms/dl, 690 nmol/l). This was especially so in 21-hydroxylase deficiency, when cortisol values should be very low. Only the luminescence and iodinated assays produced very low values after dexamethasone suppression. After the outliers had been excluded, only the iodinated assay showed a good statistical agreement with the more elaborate tritium assay. The most specific assay was the luminescence method, which produced generally lower results in most cases. This was selected as the new routine method. The unreliable cortisol results in adrenal hirsutism are attributed to high cross-reaction of the antiserum in each of the assays with 17 hydroxyprogesterone, progesterone and 21-deoxyderivatives of cortisol and deoxycorticosterone. In general, all standard and commercially available cortisol assays appears to be unsuitable for cortisol estimation in 21-hydroxylase deficiency, and probably also for neonates. PMID- 2214780 TI - Potential bile acid precursors in plasma--possible indicators of biosynthetic pathways to cholic and chenodeoxycholic acids in man. AB - The plasma concentrations of 3 beta-hydroxy-5-cholestenoic acid, 3 beta,7 alpha dihydroxy-5-cholestenoic acid and 7 alpha-hydroxy-3-oxo-4-cholestenoic acid have been compared with that of 7 alpha-hydroxy-4-cholesten-3-one in healthy subjects and in patients with an expected decrease or increase of the bile acid production. In controls and patients with liver disease, the level of 7 alpha hydroxy-3-oxo-4-cholestenoic acid was positively correlated to that of 3 beta,7 alpha-dihydroxy-5-cholestenoic acid and not to that of 7 alpha-hydroxy-4 cholesten-3-one. In patients with stimulated bile acid formation the levels of the acids were not correlated to each other but there was a significant positive correlation between the levels of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid and 7 alpha-hydroxy-4-cholesten-3-one. These findings indicate that the precursor of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid differs depending on the activity of cholesterol 7 alpha-hydroxylase. Since the activity of this enzyme is reflected by the level of 7 alpha-hydroxy-4-cholesten-3-one in plasma the findings are compatible with a formation of 7 alpha-hydroxy-3-oxo-4-cholestenoic acid from 3 beta,7 alpha-dihydroxy-5-cholestenoic acid when the rate of bile acid formation is normal or reduced and from 7 alpha-hydroxy-4-cholesten-3-one under conditions of increased bile acid synthesis. In support of this interpretation, 7 alpha,26 dihydroxy-4-cholesten-3-one was identified at elevated levels in plasma from patients with ileal resection or treated with cholestyramine. The levels of 7 alpha,12 alpha-dihydroxy-4-cholesten-3-one were also higher than normal in these patients. Based on these findings and previous knowledge, a model is proposed for the biosynthesis of bile acids in man. Under normal conditions, two major pathways, one "neutral" and one "acidic" or "26-oxygenated", lead to the formation of cholic acid and chenodeoxycholic acid, respectively. These pathways are separately regulated. When the activity of cholesterol 7 alpha-hydroxylase is high, the "neutral" pathway is most important whereas the reverse is true when cholesterol 7 alpha-hydroxylase activity is low. In cases with enhanced activity of cholesterol 7 alpha-hydroxylase, the "neutral" pathway is connected to the "acidic" pathway via 7 alpha,26-dihydroxy-4-cholesten-3-one, whereas a flow from the acidic pathway to cholic acid appears to be of minor importance. PMID- 2214782 TI - The state transitions of normal and mutant androgen-receptor complexes in human genital skin fibroblasts. AB - We have incubated cells from controls and subjects with receptor-defective androgen resistance with 3H-labelled testosterone (T), methyltrienolone (MT), dihydrotestosterone (DHT) or mibolerone (MB) and studied the temperature dependence of the dissociation rate constants of these various androgen-receptor (A-R) complexes both within cells and after they were extracted from them. In control cells, Arrhenius plots for T-, MT-, DHT- and MB-R complexes were linear and formed a hierarchy of dissociation states with energies of state IV greater than III greater than II, greater than I, respectively. Relative to this hierarchy, the dissociation states of the MB-, DHT- and MT-R complexes in mutant cells were displaced to higher, androgen-inappropriate energies in a mutant distinctive pattern. When extracted from cells control or mutant T- or MT-R complexes, and mutant (but not control) DHT- or MB-R complexes lowered their respective dissociation rates by undergoing state transitions in conformity with the hierarchy. Hence we propose that different A-R complexes reach different dissociative states by undergoing sequential transitions along a common pathway, and that these transitions are co-regulated both by the chemical characteristics of the bound androgen and by other cellular non-receptor factors. PMID- 2214783 TI - Testing for fluoxymesterone (Halotestin) administration to man: identification of urinary metabolites by gas chromatography-mass spectrometry. AB - Fluoxymesterone, an anabolic steroid, is metabolized in man primarily by 6 beta hydroxylation, 4-ene-reduction, 3-keto-reduction, and 11-hydroxy-oxidation. These pathways of metabolism are suggested by the positive identification of 4 metabolites and the tentative identification of 3 other metabolites. Detection of the drug in urine is possible for at least 5 days after a single 10 mg oral dose to previously untreated adult males, by monitoring the presence of 2 metabolites, since the parent drug is not detectable more than 1 day after the dose. PMID- 2214784 TI - In vitro inhibition by ketoconazole of human testicular steroid oxidoreductases. AB - An oral antimycotic agent, ketoconazole has been demonstrated to be an inhibitor of cytochrome P-450-dependent monooxygenases. To investigate its effect on steroid oxidoreductases, in vitro studies were carried out using subcellular fractions of human testes. Ketoconazole competitively inhibited activities of 3 beta-hydroxy-5-ene-steroid oxidoreductase/isomerase and NADH-linked 20 alpha hydroxysteroid oxidoreductase for steroid substrate and the Ki values were 2.9 and 0.9 microM, respectively. In contrast, ketoconazole inhibited neither 17 beta hydroxysteroid oxidoreductase nor NADPH-linked 20 alpha-hydroxysteroid oxidoreductase, indicating that the two 20 alpha-hydroxysteroid oxidoreductases are distinct. Further, ketoconazole inhibited non-competitively the above enzyme activities for the corresponding cofactors of NAD and NADH. From the binding mode of ketoconazole to cytochrome P-450 and the present findings, it appears likely that the agent binds to a site which is different from that of steroids or pyridine nucleotides. PMID- 2214785 TI - Alterations in the binding characteristics of glucocorticoid receptors from obese Zucker rats. AB - Obese Zucker rats appear to lack a circadian rhythm of serum corticosterone and maintain relatively high concentrations throughout the 24-h day. The binding characteristics of glucocorticoid receptors in lean and obese Zucker rats were examined in three tissues suggested to be involved in the feedback inhibition of corticosterone: the anterior pituitary, hypothalamus and hippocampus. Hepatic glucocorticoid receptors were also examined to determine if receptor alterations exist in a peripheral tissue. The dissociation constant (Kd) of glucocorticoid receptors in the anterior pituitary of obese rats was 50% greater than the Kd of receptors derived from lean rats. This suggests a decrease in the affinity of these receptors and could indicate a reduced feedback inhibition of corticosterone at the anterior pituitary. Hepatic glucocorticoid receptors of obese rats also showed an increase (150%) in the Kd of binding and a reduction (40%) in the number of receptors. No difference was observed in the Kd or maximal binding of receptors from the hypothalamus or hippocampus of lean and obese rats. It appears that glucocorticoid receptor alterations exist in obese Zucker rats and that these alterations may affect the drive of the pituitary-adrenal axis and possibly the expression of obesity. PMID- 2214786 TI - Properties of estrogen and hydroxysteroid sulphotransferases in human mammary cancer. AB - Partial purification (approximately x 140-fold) of estrogen sulphotransferase (EC 2.8.2.4) in human mammary estrogen receptor positive cancer tissue was achieved by affinity chromatography on adenosine-3',5'-diphosphate-agarose. It had a Mr of approximately 70,000 by gel filtration and upon electrophoresis on concave gradient polyacrylamide gels, showed a major (Mr 70,000) and a minor (Mr 200,000) peak of activity. Kinetics of this preparation (estradiol-17 beta and estrone as substrates), and also that of hydroxysteroid sulphotransferase (EC 2.8.2.2) contained in the cytosol of human mammary cancer MCF-7 cells (5-androstene-3 beta,17 beta-diol and dehydroepiandrosterone as substrates), were compared. The enzymes showed very similar behaviour, characterized by high affinity for their steroid substrates (low nM range) and co-operativity in their binding. For hydroxysteroid sulphotransferase, the adrenal-derived estrogen 5-androstene-3 beta,17 beta-diol was the preferred substrate compared to dehydro-epiandrosterone in the 0-40 nM concentration range. Such properties of the enzymes might be designed to limit the exposure of nuclear receptor to free ligand. Alternatively, a defined subcellular location would perhaps involve the enzymes in the elimination of estrogen after processing of the ligand-bound receptor. PMID- 2214787 TI - Preferential nuclear binding of estrogen in the formalin-fixed rat uterus. AB - Rat uterus fixed overnight in buffered formalin retains the ability to specifically bind estradiol. However, the estrogen binding property of fixed tissue appears preferentially localized in the nuclear fraction regardless of hormonal status. Furthermore, the quantity of the nuclear estrogen receptor in fresh or fixed uterus is virtually identical in the presence or absence of estrogenic hormone. Yet, while both tissue preparations exhibit equivalent increases in the total nuclear receptor occupancy after hormone exposure, only the fresh uterus contains a major cytosolic estrogen binder which decreases in availability upon the estrogen-induced elevation of the nuclear bound steroid. However, the cytosolic estrogen receptor exhibits a significant loss in its ligand binding property after formalin exposure. Thus, the preferential localization of estrogen binding in the nuclear fraction of fixed whole tissue may just reflect that only the tightly bound nuclear estrogen receptor's functional and/or structural integrity survives long-term formation fixation. Our observation of estrogen binding in preserved tissue may also be a clinically useful tool in therapy analysis. PMID- 2214788 TI - Immune reactivity in bronchogenic carcinoma and its relation to 5-year survival rate. AB - We performed a prospective study on the correlation of various parameters of the immune response with the 5-year survival rate in patients with bronchogenic carcinoma. Parameters were initially examined before starting treatment. Delayed hypersensitivity skin tests, lymphoblastogenesis, natural killer (NK) cell activity, and interleukin-2 (IL-2) production were employed to assess immune competence. Each reaction was classified into four or five grades in accordance with intensity; the 5-year survival rate of the patients showing each grade of the immune response was calculated. A correlation between response before treatment and the survival rate was most clearly noted for lymphoblastogenesis. The skin tests and the NK cell activity showed poorer correlations, and no exact correlation was noted between the IL-2 production and the immune response. PMID- 2214789 TI - Malignant melanoma occurring during pregnancy: a report of the Northern Israel Oncology Center (1968-1988). AB - Medical records of seven patients treated within a 20 year period for malignant melanoma during pregnancy were reviewed. No significant detrimental prognostic effects could be attributed to pregnancy. The current literature on melanoma and pregnancy is discussed. Based on this, pregnancy seems not to be contraindicated in melanoma patients. PMID- 2214790 TI - Symptomatic pericardial effusion in lung cancer patients: the role of fluid cytology. AB - During the years 1975-1988, twenty lung cancer patients with symptomatic pericardial effusion were treated conservatively at our center. Echocardiography demonstrated small pericardial effusion in 2 patients, medium size effusion in 3 patients and large amount of fluid in 15 patients. Fifteen patients developed cardiac tamponade; in three of these patients, this was the presenting manifestation of lung cancer. Pericardiocentesis resulted in prompt, though temporary, symptomatic relief in all patients. Fluid cytology demonstrated suspected malignant cells in 2 patients and malignant cells in 13 patients. Based on cytology, the diagnosis of adenocarcinoma was established in six patients, small cell carcinoma in three patients, and epidermoid carcinoma in one patient. All patients were dead within 9 months from the time of diagnosis of pericardial effusion; 17 died within less than 3 months. It is concluded that pericardial effusion in lung cancer is indicative of rapid tumor progression and short survival. Fluid cytology provides an immediate and accurate means of diagnosis. PMID- 2214791 TI - Renal vein leiomyosarcoma. AB - The 11th case of primary leiomyosarcoma of the renal vein is reported. Unique features of this case included concomitant resection of an isolated hepatic metastasis, intraoperative radiation therapy, and the use of electron microscopy and immunohistochemical stains in confirming the diagnosis. A review of the previously reported cases shows a tendency toward slow tumor growth and infrequent recurrence (18%). Metastases are common (82%), primarily to the lung and liver. Aggressive surgical resection and adjuvant radiation therapy, including intraoperative radiation therapy, are recommended. Adjuvant chemotherapy should be considered, although its benefits at present are unclear. PMID- 2214792 TI - Adrenal carcinosarcoma. AB - The clinical and pathologic features of a case of adrenal carcinosarcoma are reported. Although synchronous malignancy of the adrenal gland has been described, no case of an adrenal tumor combining both carcinomatous and sarcomatous elements has been previously documented. This neoplasm is extremely aggressive with distant metastasis arising from the sarcomatous component, and rapid progression despite multimodal therapy. PMID- 2214793 TI - Has preoperative radiation therapy for resectable rectal cancer been proven effective? PMID- 2214794 TI - Distinguishing malignant mesothelioma from pulmonary adenocarcinoma: an immuno histochemical approach using a panel of monoclonal antibodies. AB - A panel of six monoclonal antibodies (MAbs) was employed to evaluate antigen expression in pulmonary adenocarcinomas and mesotheliomas. Monoclonal anti-human milk fat globulin (HMFG-2), anti-carcinoembryonic antigen (NP-2), anti-epithelial membrane antigen (EMA), anti-cytokeratin (PKK-1), anti-tumor-associated antigen 72 (B72.3), and anti-human myelomonocytic antigen (Leu M-1) antibodies were used to localize their respective antigens in formalin-fixed, paraffin-embedded tumors by using the avidin-biotin-complex immunoperoxidase technique. In all, 28 mesotheliomas obtained from Ohio State University Anatomic Pathology files and from a Southwest Oncology Group (SWOG) protocol were compared to 22 pulmonary adenocarcinomas by using this MAb panel. None of the mesotheliomas demonstrated positive staining with MAbs NP-2 (anti-CEA) or Leu M-1. However, 95% (21/22) of adenocarcinomas stained with one of these two antibodies. Although neither of these two MAbs stained all adenocarcinomas, each antibody demonstrated positive immunostaining in more than 90% of the adenocarcinomas studied. Therefore, MABs NP-2 and Leu M-1 are, individually, quite useful for distinguishing mesothelioma from adenocarcinoma. However, in our study, no single MAb could be used to distinguish these two tumor types in every case. MAb B72.3 stained 91% (20/21) adenocarcinomas but also stained 7% (2/28) of mesotheliomas. MAb HMFG-2 reacted positively with 95% of adenocarcinomas, but also stained 39% of the mesotheliomas, usually in a membranous pattern. MAbs EMA and PKK-1 were not found useful in distinguishing mesothelioma from adenocarcinoma. We conclude that MAbs Leu M-1 and NP-2 were both useful in distinguishing mesothelioma from pulmonary adenocarcinoma in that positive staining was demonstrated in adenocarcinomas and not mesotheliomas. PMID- 2214795 TI - Clinicopathological features of elevated lesions of the duodenal bulb. AB - We present here our findings on patients with an elevated lesion of the duodenal bulb. All these patients were treated in our clinics between the years 1984 and 1988. These lesions were present in 36 of 8,802 patients who underwent upper gastrointestinal pan-endoscopy. Two patients had a duodenal carcinoma, 2 an adenoma, and 1 a Brunner's gland adenoma. There were 15 with a hyperplastic polyp, 3 with a heterogenic gastric mucosa, 3 with Brunner's gland hyperplasia, 6 with duodenitis, and 4 with regenerative mucosa. Among these 36 lesions, only 69% (25 lesions) were evident on the upper gastrointestinal X-ray series. Adenoma and Brunner's gland adenoma were of a pedunculated form of the gross type and had an irregular surface mucosa. Both duodenal carcinomas were detected by endoscopic biopsy and were resected. Histologically, these lesions were limited to the submucosal layer and were of the non-pedunculated polypoid form, but there were no other characteristic endoscopic features, in comparison with other elevated lesions. Thus, upper gastrointestinal endoscopy with routine observations of the duodenal bulb plus endoscopic biopsy will lead to a definite diagnosis of these elevated lesions and to the early detection and treatment of this rare malignant lesion. PMID- 2214796 TI - Utility of surgical margins in the radiotherapeutic management of soft tissue sarcomas. AB - Seventy-four adult patients with localized soft tissue sarcomas were treated with radiation therapy following surgery between 1965 and 1988. Fifty-three were treated after the first excision of their tumor with 6 (11.3%) local recurrences. Twenty-one received radiation after excision of recurrent disease with 11 (52.4%) local failures (P less than .0005). Metastatic disease occurred in 14 (26.4%) of the primary tumors and 8 (38.1%) with multiple previous excisions (P less than .48). Of those patients treated for primary sarcoma, there were no local failures with pathologically wide margins or if a single margin was microscopically positive. Local failure occurred in 4 of 26 (15.4%) if the tumor was merely enucleated and in 2 of 11 (18.2%) who had grossly positive surgical margins (P not significant). Local failure was also more common in truncal locations (33.3%) as compared with extremity locations (8.7%, P = .1359). Additional factors analyzed which adversely affected prognosis included tumor grade, stage, and inadequate radiation dose. PMID- 2214797 TI - Acral melanoma: a review of 185 patients with identification of prognostic variables. AB - One hundred eight-five patients with acral melanoma treated since 1972 were reviewed. These included 53 subungual lesions, 123 plantar lesions, and 9 palmar lesions. Eighty percent presented with stage I disease. Mean age was 57 years. Males outnumbered females 1.1:1. Seventeen percent (17%) were blacks. Actuarial 10-year survival was 58% for stage I patients and 35% for stage II patients. Univariate Cox regression analyses identified 5 prognostic variables affecting survival: stage at diagnosis (P less than 0.001), race (P less than 0.001), ulceration (P = 0.012), Clark's level (P = 0.014), and thickness of the primary lesion (P = 0.013). Factors unrelated to survival included sex of the patient, site (volar vs. subungual), histology, and treatment with amputation. Multivariate analysis for patients with stage I lesions identified race (P = 0.001) and ulceration (P = 0.018) as significant variables, with thickness approaching significance (P = 0.094). In an additional series of 71 patients with melanomas arising from extremity sites near the junction of glabrous and non glabrous skin, survival was significantly poorer for those arising from glabrous skin (P = 0.024), and reflects a higher incidence of metastatic disease at diagnosis. Specific active immunotherapy was the principal adjuvant used for these patients, and survival was comparable to that reported with regional perfusion therapy. Acral melanoma a) has a strong racial predilection, b) carries a grave prognosis, and c) arises from glabrous skin. It is a clinical entity distinct from other extremity melanomas. Surgical management with either wide excision or amputation is appropriate for the primary lesion. PMID- 2214798 TI - Long-term experience with a totally implanted catheter system in cancer patients. AB - Long-term experience with totally implanted catheter systems (TICS) is limited. We retrospectively evaluated the performance and long-term complications of TICS for intravenous infusion in cancer patients; 134 systems were implanted in 128 patients. The median duration of implantation was 144 weeks with 49 systems implanted for more than one year. Complications related to surgical factors included malposition of reservoir (2%), skin perforation or wound dehiscence (1.5%) and pneumothorax (less than 1%). Complications not related to surgical factors included: drug extravasation (1.5%), mechanical malfunction (1.5%), vein thrombosis (less than 1%), clotting of the reservoir or catheter (2%), skin infection (1.5%), and sepsis (less than 1%). The total complication rate was 13%. Most complications resolved spontaneously or with medical treatment and only 6 patients (4.6%) required re-implantation of a second system. We conclude that with long-term usage of TICS, the complication rate remains low, making it a safe and viable alternative for patients requiring long-term intravenous therapy. PMID- 2214800 TI - Simple method to produce acute heart failure by coronary vessel embolization in closed chest rats with microspheres. AB - Changes in left ventricle (LV) function, systemic, and regional hemodynamics as a result of coronary artery embolization by 15 microns microspheres were studied in rats. Selective coronary embolization was produced by injection of microspheres during ascending aorta occlusion animals by using an "L"-shaped wire in closed chest animals. Maximal developed LV systolic pressure (LVSPmax) was determined during ascending aorta occlusion. Coronary embolization evoked reductions in LVSPmax and +dP/dtmax and then decreased in basal LVSP, dP/dtmax, dP/dtmax/P, with a parallel increase in LV end-diastolic pressure (LVEDP). The number of microspheres accumulating in the heart following coronary embolization was about 40% of the total amount of the injected microspheres (300,000-400,000). In conscious rats 48 hr after coronary vessel embolization (in LV myocardium 100,003 +/- 4,334 microspheres per gram) the cardiac index, mean arterial pressure, dP/dtmax and stroke volume were reduced by 35.6%, 20%, 17.2%, and 26.7%, respectively, when compared with sham-operated rats. LVEDP was increased by 40%, when compared with sham-operated rats. These results show that in this rat model of coronary vessel embolization heart failure develops. The model created may be used for the studies of pathophysiology of acute heart failure as well as for screening new compounds potentially effective in heart failure. PMID- 2214799 TI - New chronic gastric cannula for feeding ethanol liquid diet to young and old rats. AB - Fifty-eight male Fischer-344 rats ages 5 and 23 mo were fed a liquid diet containing ethanol for 6 wk by means of a newly designed chronic gastric cannula that permitted maximum allowable freedom with minimum stress. Rats were weaned onto the Lieber-DeCarli diet and fed 10 mL three times daily by bolus injection. With or without ethanol, the minimum daily intake of calories necessary to maintain body weight was determined to be approximately 150-160 kcal/kg/day for the young adult rats and 120-125 kcal/kg/day for the aged animals. PMID- 2214801 TI - Cecectomized rat. A model of experimental secretory diarrhea in conscious animals. AB - Evaluation of antisecretory antidiarrheal agents in animal models is limited primarily to extrapolations of efficacy from enteropooling studies in vivo, isolated intestinal loops in situ, and Ussing flux chamber preparations in vitro. While these standard techniques are useful, they do not mimic secretory diarrhea. Our studies indicate that in rats, the cecum may serve a "reservoir" function in response to secretagogue administration. Thus, diarrhea is not observed consistently and reliably in this species to allow valid evaluation of potential antidiarrheal agents. Therefore, we have developed a reproducible model of secretory diarrhea utilizing conscious cecectomized rats by surgical resection of the cecum, without compromising ileocecal patency, and by the use of potent intestinal secretagogues. Animals quickly recover and maintain normal growth and other physiologic parameters for as long as 60 days. After 48 hr on standard chow, secretory diarrhea can be induced by oral administration of standard intestinal secretagogues (dimethyl prostaglandin E2, cholera toxin, or carbachol). Dimethyl prostaglandin E2 (300 micrograms/kg, p.o.) induces diarrhea within 1 hr that continues for approximately 3.5 hr. Oral administration of known antidiarrheal agents chlorpromazine (10 mg/kg), clonidine (1 mg/kg), or morphine (10 mg/kg) all significantly reduce fecal output within 30-60 min following administration. These studies indicate that in the rat, the cecum may serve as a fluid reservoir during periods of small intestinal hypersecretion and that the cecectomized rat serves as a useful, accurate, and reliable tool for evaluating new compounds with proposed antidiarrheal activity. PMID- 2214802 TI - Computer-based quantitative morphometric analysis of the dynamic characteristics of indomethacin and ethanol-induced gastric lesions in the rat. AB - A computerized morphometric analysis was used to measure the gastric lesions in rats induced by oral administration of 2 mL of 100% EtOH or indomethacin 80 mg/kg. In both cases, the lesions were followed over a period of several days to determine their time course characteristics. Indomethacin lesions were present 1 hr after the administration of the drug and reached a peak after 6 hr. Ethanol lesions appeared as early as 1 min after administration and were fully expressed after 1 hr. Recovery of the gastric mucosa was observed after 2 and 6 days, respectively. The use of this computerized systems allows precise measurements of gastric lesions and facilitates the evaluation of the effect of drugs in the gastrointestinal tract. PMID- 2214803 TI - Screening procedure for assessment of ototoxicity in the common marmoset. AB - Detection of drug-induced ototoxicity in safety evaluation studies of novel chemical entities is rarely attempted. Where such examinations are included, they usually rely on reflex testing. The Brainstem Auditory Evoked Response can be measured with the use of externally positioned electrodes, and it monitors electrophysiologic responses to sound from the cochlear nerve and associated structures of the 8th cranial nerve. These responses have been reproducibly measured in sedated marmosets and the method shown to be a sensitive detector of hearing loss caused by loop diuretics or aminoglycoside antibiotics. additionally, where hearing damage is reversible, recovery can also be monitored. It is proposed that where a sensitive marker for ototoxicity is considered necessary as part of a multifaceted study investigating in vivo drug safety, this procedure may prove advantageous over existing methods. PMID- 2214804 TI - Kinetics of the trypsinogen activation by enterokinase and trypsin. AB - A global kinetic analysis of the mechanisms of the trypsinogen activation by enterokinase and trypsin is presented. The kinetic equations of both the transient-phase and the steady-state of these mechanisms are presented. In addition, we here derive the corresponding kinetic equations for the case in which the condition of rapid equilibrium prevails and we propose a kinetic data analysis. The significance of this approach to the treatment of other zymogen activation processes is discussed. PMID- 2214805 TI - Resistance of native protein shapes to random single point mutations in their genes. PMID- 2214806 TI - Movement of actin filaments along tracks of myosin heads. PMID- 2214807 TI - When to copy or avoid an opponent's strategy. AB - Models of two-player games are analyzed in which contestants strive to maximize relative success (market share). Each contestant divides its resources among a set of investment strategies. For a particular investment strategy the contestants may receive different expected rates of return. Each strategy also returns to both contestants an additional payoff that is unpredictable. Depending on particular assumptions, a contestant may maximize relative success by copying or avoiding its opponent's allocation pattern. In other cases a contestant may be favored to diversify its investments equally among strategies and minimize its total variance in returns, or to invest only in one strategy and maximize its total variance in returns. PMID- 2214808 TI - Kinetics of the classical complement activation cascade. AB - Transient-phase and steady-state equations have been derived for the classical complement activation mechanism. From these equations the corresponding ones for the rapid equilibrium conditions have been derived. We propose an experimental design to determine the kinetic parameters. PMID- 2214809 TI - Nash equilibrium and evolutionary stability in large- and finite-population "playing the field" models. AB - This paper studies the correspondence between Nash equilibrium and evolutionary stability in large- and finite-population "playing the field" models. Whenever the fitness function is sufficiently continuous, any large-population ESS corresponds to a symmetric Nash equilibrium in the game that describes the simultaneous interaction of the individuals in the population, and any strict, symmetric Nash equilibrium in that game corresponds to a large-population ESS. This correspondence continues to hold, approximately, in finite populations; and it holds exactly for strict pure-strategy equilibria in sufficiently large finite populations. By contrast, a sequence of (mixed-strategy) finite-population ESSs can converge, as the population grows, to a limit that is not a large-population ESS, and a large-population ESS need not be the limit of any sequence of finite population ESSs. PMID- 2214810 TI - Testing and characterizing the two-stage model of carcinogenesis for a wide range of human cancers. AB - The age dependence of incidence for 45 cancer types in three populations is analyzed on a two-stage kinetic model containing three determinable parameters: (i) the fraction of population at risk for a cancer; (ii) the product of the frequencies of cancer-producing mutations, and (iii) the growth rate of the transformed clone from which a cancer ultimately evolves. The model, simplifying that proposed by others, fits many cancers. Data are easily handled in terms of the derived parameters, providing the basis for epidemiological analysis, here applied in detail to liver, cervix and testis cancers for nearly 50 world-wide populations. We identify 12 cancers for which only a limited fraction of the population is at risk. We argue that the appearance of most cancers requires at least three mutational events. For child, youth, or early adult cancers, one mutation may be congenital. We arrange the various cancers in a descending scale, defining six groups that differ in the derived mutation frequencies. A cancer appearing later in life, for which the whole population can be at risk, shows a low mutation frequency, consistent with background spontaneous mutation. The other cancers require increases in mutation frequency, arising from an increased rate of cell division and/or mutation rate. PMID- 2214811 TI - Mucilaginous plants and their uses in medicine. AB - Throughout the world but especially in the tropical and subtropical zones, there are succulent and non-succulent plants which harbor readily releasable mucilage in their tissues, on the surface of their seeds or in their bark. This mucilage may have diverse practical uses. Among these, it functions as a healing agent, casually or in the practice of traditional-folk or conventional medicine. The mucilage of some of these plants is well known to science and has been studied by pharmacologists and found to possess biologically active principles. However, they all have in common a beneficial effect on burns, wounds, ulcers, external and internal inflammations and irritations, diarrhea and dysentery. This paper presents examples of such plants belonging to 19 botanical families, with a view to calling attention to the similar uses of easily extracted plant mucilages and, particularly, their ability to provide protection from fire, a feature which has already been demonstrated in Australia. PMID- 2214812 TI - Ginger (Zingiber officinale) in migraine headache. AB - Migraine is considered as a neurological disorder with little convincing evidence of the involvement of some vascular phenomenon. Recent understanding of the mechanisms behind migraine pain generation and perception have considerably helped the development of modern migraine drugs. Most migraine drugs in use, i.e., ergotamine and dihydroergotamine, iprazochrome, pizotifen and diazepam; and non-steroidal antiinflammatory drugs (i.e. aspirin, paracetamol, persantin, etc.) have side-effects and are prescribed with caution for a limited duration. Ginger is reported in Ayurvedic and Tibb systems of medicine to be useful in neurological disorders. It is proposed that administration of ginger may exert abortive and prophylactic effects in migraine headache without any side-effects. PMID- 2214813 TI - New experimental model for the evaluation of adaptogenic products. AB - A new animal model for evaluating improvement in physical work performance and endurance in an adverse environment is described. In this model, rats in restraint were exposed to 5 degrees C at 480 mmHg atmospheric pressure. Results were compared to an animal forced to swim in water at 23 degrees C. In both the models, colonic temperature (Tr) of the rats was continually monitored during exposure to adverse environment and during recovery at 32 degrees C and normal atmospheric pressure. The time and pattern for Tr fall to 23 degrees C and its recovery to 37 degrees C were used as measures of endurance. The cold-hypoxia restraint model was found to provide more precise results compared with the cold swimming model. Panax ginseng root and Ginkgo biloba leaf extracts were compared for their positive endurance-promoting properties using both models. PMID- 2214814 TI - New procedure for direct bioautographic TLC assay as applied to a tincture of Ranunculus bulbosus. AB - A new procedure for TLC bioautographic assay using a flooding method to inoculate the developed plates is described. Details about several microbiological parameters allow good reproducibility for this method which appears rapid, easy to perform and requiring no specialized equipment. Significantly results obtained with a commercial tincture of Ranunculus bulbosus illustrate this method which can be extended to complex mixtures of natural products in order to isolate active fractions. PMID- 2214815 TI - Topical antiinflammatory effects of Euphorbia prostrata on carrageenan-induced footpad oedema in mice. AB - The ethyl acetate extract and a fraction, KSE-23, isolated chromatographically from the ethyl acetate extract of Euphorbia prostrata, showed significant antiinflammatory activity when topically applied in a murine model of carrageenan footpad oedema. KSE-23 was found to be more potent than indomethacin given in the same manner. PMID- 2214816 TI - Plants used in traditional medicine in eastern Tanzania. IV. Angiosperms (Mimosaceae to Papilionaceae). AB - Sixty-nine Angiosperms (Mimosaceae to Papilionaceae) are listed, which are used by traditional healers in five regions of Eastern Tanzania; namely, Coast, Dar es Salaam, Kilimanjaro, Morogoro and Tanga. For each species listed, the botanical name, vernacular name, collection number, locality, habit, distribution and medicinal uses are given. Additionally, information from the literature on medicinal uses, chemical constituents, and pharmacological effects are also provided. PMID- 2214817 TI - Antifungal activity of Cassia alata leaf extract. PMID- 2214819 TI - Plants in the traditional medicine of the Ubaye Valley. AB - The study of the traditional pharmacopoeia in the Ubaye Valley (in the Alpes de Haute Provence department) enabled us to draw up a table showing 136 medicinal plants, their vernacular names, their suitable parts, the instructions for use, the medical purposes and the principal pharmacological and therapeutical properties. This study points out the close connection between plants, pathology and the living conditions of an agro-sylvo-pastoral civilization. PMID- 2214818 TI - Intestinal motility enhancing effect of Atractylodes lancea rhizome. PMID- 2214820 TI - Intestinal smooth muscle spasmolytic actions of the aqueous extract of the roots of Taverniera abyssinica. AB - A room temperature aqueous extract of the roots of Taverniera abyssinica antagonized the contractile responses of the guinea-pig ileum to acetylcholine and histamine. The extract also relaxed the smooth muscle of the rabbit duodenum, abolished the pendular contractions and antagonized the effects of acetylcholine and histamine on this tissue. The results confirm that there may be a sound pharmacological basis for the ethnomedical use of the roots of this plant to treat stomach ache. PMID- 2214821 TI - Tabernaemontana crassa as a traditional local anesthetic agent. PMID- 2214822 TI - Effects of an aqueous extract of Ferula ovina on rabbit and guinea pig smooth muscle. AB - The effects of an aqueous extract of Ferula ovina were tested in vitro using isolated segments of rabbit and guinea pig intestine, trachea and aorta. The extract inhibited the spontaneous movements of rabbit jejunum and guinea pig ileum and the contractions induced by acetylcholine. The aqueous extract also inhibited the contractions of rabbit trachealis muscle induced by acetylcholine and the contractions of guinea pig trachealis muscle induced by histamine. These inhibitions were dose-dependent and reversible. However, the aqueous extract did not inhibit the contractions of rabbit and guinea pig aortic rings induced by norepinephrine. These data suggest that this plant has non-specific anticholinergic and antihistaminic antispasmodic effects. PMID- 2214824 TI - Plants used in Guatemala for the treatment of gastrointestinal disorders. 1. Screening of 84 plants against enterobacteria. AB - Gastrointestinal disorders are important causes of morbidity in developing countries. Natural healing is the traditional way of treating these diseases in Guatemala. Ethnobotanical surveys and literature reviews showed that 385 plants from 95 families are used in Guatemala for the treatment of gastrointestinal disorders. The activity of 84 of the most commonly used plants was screened in vitro against five enterobacteria pathogenic to man (enteropathogenic Escherichia coli, Salmonella enteritidis, Salmonella typhi, Shigella dysenteriae and Shigella flexneri). Results indicate that 34 (40.48%) plants inhibit one or more of the enterobacteria tested. The most commonly inhibited bacterium was S. typhi (33.73%) and the most resistant was E. coli (7.35%). The plants of American origin which exhibited the best antibacterial activity were: Byrsonima crassifolia, Diphysa robinioides, Gnaphalium stramineum, Guazuma ulmifolia, Psidium guajava, Sambucus mexicana, Simarouba glauca, Smilax lundelii, Spondias purpurea and Tagetes lucida. These results indicate a scientific basis for use of these medicinal plants for attacking enterobacterial infections in man. PMID- 2214823 TI - Pharmacology of an Indian-snuff obtained from Amazonian Maquira sclerophylla. AB - The powdered bark of Maquira sclerophylla is consumed as snuff in north Brazil. Both the crude and the purified hydrosoluble extract (WP) injected i.p. in the dose range of 0.05-0.5 g/kg induced hyperexcitability, tremors, motor incoordination, ataxia, quietness and muscle relaxation in rats. The effects were progressive, dose-related and reversed after 30 min. Anesthetized rats, guinea pigs and dogs injected with the purified extract (10-50 mg/kg, i.v.) showed a biphasic change of carotid blood pressure. The early and transient hypotension was blocked by atropine but not by vagotomy: the secondary hypertension was long lasting and sustained for over 30 min. The hypertension was shortened but not blocked after ganglionic blockade or reserpine treatment. Either pithing or alpha receptor blockade with yohimbine reduced both effects of the extract. Guinea-pigs and dogs were more responsive than rats and died by heart arrest. Incubation of WP (20 micrograms/ml) increased both the rate and force of contraction of isolated guinea-pig right atria by 2 and 5 times, respectively. Propranolol (4 micrograms/ml) blocked the chronotropic effect but did not decrease the inotropic effect. In electrically driven guinea-pig left atria, WP (10 micrograms/ml) increased the force of contraction by 80% and the maximum rate of force development by 60%, but did not change the time to peak tension, the time to 50% relaxation, or the rate of relaxation. These cardiovascular effects resemble those of digitalis-like drugs. Cardenolides were detected in WP by phytochemical screening. PMID- 2214825 TI - Quantitative estimation of Holarrhena antidysenterica bark total alkaloids in crude drugs and in the body fluids of man and rat. AB - A turbidimetric method was developed for the quantitative estimation of the total alkaloids of kutaj bark (Holarrhena antidysenterica) in crude medicinal preparations and in the body fluids of man and rat. The alkaloids were colloidally precipitated with Dragendorff's reagent as complex salts of potassium iodobismuthate in extremely dilute solutions. The finely subdivided orange-brown precipitate gave a coloured, clear homogeneous suspension in the presence of gum arabic. Optical density of such suspensions changed linearly with the change in alkaloid concentration, when prepared within the standardized experimental conditions that included control of ion concentration and temperature of the reaction mixture. Observations revealed the reversible nature of the alkaloid reagent reaction. Crude medicinal preparations from three different pharmaceutical sources contained varying concentrations of the alkaloids. Complete recovery of the alkaloids was possible from plasma and urine, while significant amounts of the alkaloids were lost to blood cells and faecal contents in man and rat. PMID- 2214826 TI - Induction of neutrophil accumulation by Chinese herbal medicines "hochu-etsuki to" and "jyuzen-daiho-to". AB - "Hochu-etsuki-to" (HT) and "Jyuzen-daiho-to" (JT) are Chinese herbal medicines that have been used for the treatment of weakened physical strength and asthenic persons. Intraperitoneal injection of boiled water extracts in mice of HT and JT were found to induce a high accumulation of neutrophils 6 h after injection in a manner similar to that seen with the biological response modifier lentinan. The neutrophil accumulation by intraperitoneal injection of HT and JT increased dose dependently. PMID- 2214827 TI - Effect of Melothria maderaspatana on carbon tetrachloride-induced changes in rat hepatic microsomal drug-metabolizing enzyme activity. AB - Treatment with an aqueous extract of the aerial parts of Melothria maderaspatana, before or after CCl4 administration in rats markedly decreased CCl4-mediated reductions in aniline hydroxylase and p-aminopyrine N-demethylase activities. Phenobarbital-induced sleeping time in rats and kinetic enzyme studies showed that the effect of the plant was neither due to an induction of the drug metabolizing enzymes nor due to an alteration in the Km values of the enzymes. PMID- 2214828 TI - Extracorporeal membrane oxygenation for the circulatory support of children after repair of congenital heart disease. AB - We have treated 39 infants and children with congenital heart disease with extracorporeal membrane oxygenation during the past 5 years. Thirty-six were treated for low cardiac output or pulmonary vasoreactive crisis after repair of congenital heart defects. Twenty-two (61%) survived. Most patients were cannulated from the neck via the right internal jugular vein and the right common carotid artery. Six patients were cannulated from the chest, including three who had separate drainage of the left side of the heart with a left atrial cannula. Two of these patients survived and were the only survivors of the nine patients cannulated in the operating room because they could not be weaned from cardiopulmonary bypass after open cardiac operations. We also reviewed 312 patients (the predictor study series) having open cardiac operations before the availability of extracorporeal membrane oxygenation; 27 of these patients died. Data were collected at 1 and 8 hours postoperatively to determine if any parameters might predict early mortality. With these parameters used as criteria, patients who went on extracorporeal membrane oxygenation were as sick as those who died before extracorporeal membrane oxygenation was available. The most common complication was bleeding related to heparinization. The mean transfusion requirement in survivors was 1.50 +/- 1.13 ml/kg/hr, 5.63 +/- 7.0 ml/kg/hr in the nonsurvivors, and 7.46 +/- 8.29 ml/kg/hr in those cannulated in the operating room because they could not be weaned from bypass. Four children had intracranial hemorrhage, and two of them died. There was one late death. Nine of the 22 survivors are entirely normal. All survivors who do not have Down's syndrome are considered to have normal central nervous system function. We conclude that extracorporeal membrane oxygenation can improve survival in patients with both pulmonary artery hypertension and low cardiac output after operations for congenital heart disease. PMID- 2214829 TI - Long-term results of the Belsey Mark IV antireflux operation in relation to the severity of esophagitis. AB - A retrospective analysis of the results of the Belsey Mark IV operation has been conducted, relating these to the degree of esophagitis present preoperatively. Analysis of 89 patients showed a 91.7% success rate in patients without esophagitis. Good results diminished steadily as the severity of esophagitis increased, giving 76.5%, 75%, 66.7%, and 50% success rates for first-, second-, third-, and fourth-degree esophagitis, respectively. We believe that shortening of the esophagus is an important factor in this. Shortening is obvious in third- and fourth-degree esophagitis but subtle in first- and second-degree esophagitis. We conclude that the Belsey operation is adequate for patients without esophagitis, but for patients with any degree of esophagitis more effective reflux control is needed. PMID- 2214830 TI - The metabolic consequences of a "washed" cardiopulmonary bypass pump-priming fluid in children undergoing cardiac operations. AB - The substrate load of the pump-priming fluid, especially glucose and lactate, has a major influence on the metabolic response of children during cardiac operations and may be detrimental neurologically. It is possible to cleanse the priming fluid of these excess substrates by ultrafiltration followed by the addition of a balanced electrolyte solution. We have used this technique in the bypass management of nine children over 1 year of age and weighing less than 18 kg who were studied from induction of anesthesia to 6 hours postoperatively. Frequent blood samples were taken for measurement of electrolytes, intermediary metabolites, and stress-related hormones. Throughout the study period electrolyte concentrations were maintained within the physiologic range and changes in blood glucose and lactate were minimized compared with those of matched historical controls from previous studies. During the period of cardiopulmonary bypass mean serum glucose concentrations varied between 4.4 and 7.7 mmol/L and peaked at 10.7 mmol/L just before skin closure. The mean serum lactate concentration did not exceed 2.3 mmol/L during the period studied. Thus ultrafiltration of the priming fluid and replacement with a balanced electrolyte solution results in the delivery to the patient of a reasonably physiologic substrate load, which is reflected in improved control of mean plasma intermediary metabolite concentrations. The method may form the basis of further clinical studies to determine specific aspects of the metabolic stress response in children. PMID- 2214831 TI - Prostacyclin and prostaglandin E2 mediate reduction of increased mean arterial pressure during cardiopulmonary bypass by aspiration of shed pulmonary venous blood. AB - Increased mean arterial pressure during the aortic crossclamp period while on cardiopulmonary bypass was usually treated by us with hypotensive drugs. We noticed, however, that aspirating shed excess pulmonary venous blood from the open pleural cavities causes an immediate reduction in mean arterial pressure, obviating the need for any further pharmaceutical intervention. In this study we investigated the relationship between the reduction in mean arterial pressure and the levels of prostacyclin and prostaglandin E2 in the peripheral and pulmonary venous blood. Ten men undergoing coronary bypass operations had 21 episodes of increased mean arterial pressure (106.9 +/- 11.4 mm Hg) during aortic crossclamping, which was reduced to 67.4 +/- 11.4 mm Hg (p less than 0.001) only by aspirating a mean of 490 ml (range 150 to 1100 ml) of pulmonary venous blood from the pleurae back into the circulation. Mean peripheral prostacyclin level, measured as 6-keto-prostaglandin F1 alpha, and prostaglandin E2 level, both measured by radioimmunoassay technique, were significantly lower at peak mean arterial pressure (419 +/- 180 and 59.5 +/- 21.2 pg/ml) than at lowest mean arterial pressure (632 +/- 271 and 96.7 +/- 52.4 pg/ml for 6-keto-prostaglandin F1 alpha and prostaglandin E2, respectively; p less than 0.001). Prostaglandin F1 alpha and prostaglandin E2 levels in the aspirated pulmonary venous blood were 2309 +/- 3098 pg/ml and 749 +/- 909 pg/ml, respectively. The hypotensive effect of shed pulmonary venous blood that is aspirated back from the pleurae into the circulation seems to be mediated by the high levels of prostacyclin and prostaglandin E2, both powerful vasodilators. PMID- 2214832 TI - Myocardial temperature during cardiac operations: influence on right ventricular function. AB - Maintenance of right heart integrity is frequently neglected during coronary operations. Right ventricular dysfunction sometimes limits the success of the surgical procedure, however. In addition to the use of cardioplegic solutions, myocardial hypothermia during ischemic cardiac arrest seems to be an important factor for guaranteeing right ventricular performance thereafter. This study was designed to measure myocardial temperature in patients with coronary artery disease who have significant stenosis of the right coronary artery in comparison with those who do not have stenosis of the right coronary artery and to evaluate the influence of myocardial temperature on right ventricular hemodynamics after cardiopulmonary bypass. Right ventricular function was assessed by thermodilution technique, which allows measurement of right ventricular ejection fraction, right ventricular end-diastolic volume, and right ventricular end-systolic volume. Right ventricular temperature differed significantly between the two groups, with the lowest value of 15.1 degrees +/- 1.8 degrees C in the group without stenosis of the right coronary artery and a value of 22.2 degrees +/- 2.1 degrees C in the group with stenosis of the right coronary artery. Left ventricular and septal temperatures were without group differences within the investigation period. Right ventricular hemodynamics were impaired only in the group with stenosis of the right coronary artery with a decrease in right ventricular ejection fraction from 44.2% to 34.1% immediately after termination of bypass and an increase in right ventricular end-diastolic volume index (+38%) and right ventricular end systolic volume index (+70%). Cardiac index decreased only in this group, too ( 22.5%). Analysis of covariance revealed a significant correlation only between changes in right ventricular ejection fraction, right ventricular end-diastolic volume, and right ventricular end-systolic volume and the course of right myocardial temperature. It is concluded that right ventricular hypothermia is more difficult to achieve in patients with a diseased right coronary artery. Constant myocardial hypothermia, however, seems to be important in guaranteeing right ventricular function, which easily can be evaluated by the thermodilution technique. PMID- 2214833 TI - Functional consequences of the right ventricular isolation procedure. AB - The right ventricular free wall was surgically isolated from the remainder of the heart in eight dogs to evaluate the functional consequences of this procedure. Each dog was instrumented with ultrasonic dimension transducers in the right and left ventricular free walls, intracavitary micromanometers, and pulmonary artery flow probes. Volume loading and vena caval occlusions were performed to assess diastolic compliance and systolic function. Right ventricular unstressed myocardial segment length increased from 14.2 +/- 0.7 to 15.0 +/- 0.8 mm (p less than 0.5). There was an accompanying significant postoperative loss of right ventricular diastolic compliance (p less than 0.005). Regional right ventricular systolic function and regional left ventricular diastolic compliance and systolic function were preserved after the procedure. Postoperatively, when the right ventricular free wall was not paced and left silent, right ventricular stroke work decreased from 7.0 +/- 0.8 to 2.7 +/- 0.5 gm-m/m2 (p less than 0.05). These data demonstrate that the diastolic compliance of the right ventricular free wall decreases significantly after right ventricular isolation. However, there were no changes in regional right ventricular systolic or regional left ventricular function. The isolated right ventricular free wall contributes significantly to postoperative cardiac performance. PMID- 2214834 TI - Is cutting stress responsible for the limited durability of heart valve bioprostheses? AB - The limited durability of the valve bioprostheses made from calf pericardium is partially due to the calcification of this biomaterial and to mechanical fatigue of the tissue. The object of this study is to determine the harmful effect on the pericardial membrane of cutting caused by the suture thread by showing the different elastic behaviors of the biomaterials employed. This cutting stress is established during the process of molding the valve leaflet, creating a vulnerable point from the very moment of construction, which is an important factor in the limited duration of the bioprosthesis. PMID- 2214835 TI - Development of a new surgical procedure for repairing tracheobronchomalacia. AB - We have developed a new surgical method for repairing tracheobronchomalacia. In experiments on dogs we tried external fixation of Marlex mesh (Bard Cardiosurgery Division, Bellerica, Mass.) on the trachea. We first made models of tracheomalacia by making fractures or resections in intrathoracic tracheal cartilages and then made an external fixation of Marlex mesh on the malacic segments of the trachea. In 11 dogs Marlex mesh was sutured onto the trachea with absorbable thread. The trachea was firmly supported after 2 to 6 months, compared with three controls in which no external fixation was made. However, mucosal defects associated with ischemia caused by the suture developed in four of the 11. In 13 more dogs Marlex mesh was bonded to the trachea with fibrin glue. After 3 to 8 months the supporting strength of the trachea increased up to the level of the normal trachea. There was no evidence of inflammation or of mucosal defects. Therefore Marlex mesh was applied to a 44-year-old-man who had experienced frequent attacks of cough syncope. After the operation the attacks of cough syncope and collapsing of his airway disappeared completely. PMID- 2214836 TI - Prediction of risk in noncardiac operations after cardiac operations. AB - To determine the preoperative variables affecting the mortality rate and the development of severe complications in patients who have had myocardial revascularization or a valve replacement and who then undergo a noncardiac operation, we retrospectively studied data from 120 such patients over the 5 years from 1982 through 1986. Thirty-six percent of patients had a noncardiac operation during the first month after the cardiac operation. The mortality rate was 11%, and the morbidity rate was 56%. The statistical comparison of the predictive accuracy of postoperative complications of three simple, widely used classifications (American Society of Anesthesiologists physical status, New York Heart Association classification, Massachusetts General Hospital cardiac risk index) demonstrated the superiority of the simplified three-class cardiac risk index (Massachusetts General Hospital-cardiac risk index; predictive accuracy of 84%). In a multivariate discriminant analysis of 21 variables in this population, five variables (myocardial infarction in previous 6 months, S3 gallop or jugular vein distention, arrhythmia on last preoperative electrocardiogram, emergency operation, delay between cardiac and noncardiac operation) were identified as being the most predictive of a postoperative complication. When these variables were used in the function (DF3) obtained by linear discriminant analysis, the prediction accuracy of a postoperative complication reached 83%. Performance of the new models in a prospective validation population remained satisfactory (75% for Massachusetts General Hospital-cardiac risk index three-class index and 72% for DF3). Extensive statistical analysis of our data tested by a validation study provided simple predictive models based on clinical variables easily available even in emergency situations. PMID- 2214837 TI - Intraoperative coronary artery endarterectomy with excimer laser. AB - Compared with continuous-wave lasers, excimer lasers exhibit several in vitro advantages: nonthermal ablation process and linear relation between the number of pulses and the depth of the crater. A 308 nm, 20 nsec pulse duration, 1 to 5 repetition rate laser was specifically designed for clinical application. At the time of cardiopulmonary bypass in 10 symptomatic patients, before bypass grafting, a 1 mm diameter core specifically ultraviolet-tipped fiberoptic scope was introduced via the coronary arteriotomy and placed upstream (seven patients) and downstream (three patients) in contact with the stenosis. Laser power was increasingly delivered up to the clearing of the stenosis or occlusion. Quality of angioplasty was controlled by calibration of the neolumen, cardioplegic solution output through the laser-treated segment, and an eighth day or sixth month coronary arteriogram. In the first three patients studied on the eighth day, all laser-treated coronary artery segments showed an early parallel-linked patent neolumen despite competitive bypass graft flow. In the patients studied after 6 months, all recanalized segments were patent except one; in one patient the venous graft was occluded, but the upstream laser angioplasty was patent. The main limitation of the method lies in the fact that laser coronary recanalization is confined to the fiber core diameter. We conclude that (1) excimer laser angioplasty may be safe and efficient during surgical procedure and (2) as catheter flexibility remains the most critical problem, we are now assuming an appropriate tool with a multifiber system that is suitable for intraoperative as well as percutaneous routes. PMID- 2214838 TI - Pleuroperitoneal shunt for persistent pleural drainage after Fontan procedure. AB - Persistent effusions of chylous fluid may prolong the hospitalization period of many patients who have had a Fontan procedure. Herein we report the case histories of two patients in whom use of a pleuroperitoneal shunt to control the effusion shortened the hospital stay by several weeks. PMID- 2214839 TI - Invited letter concerning: Long-term results of the Belsey Mark IV antireflux operation in relation to the severity of esophagitis. PMID- 2214840 TI - Medtronic Intact porcine valve thrombosis. PMID- 2214841 TI - Functioning paraganglioma (pheochromocytoma) of the thorax: preoperative embolization. PMID- 2214842 TI - Reply to invited letter concerning: Endothelial preservation in human saphenous veins (J Thorac Cardiovasc Surg 1990;100:149-50) PMID- 2214843 TI - Reply to: Amiodarone and quinidine for postoperative atrial arrhythmias (J Thorac Cardiovasc Surg 1990;99:942) PMID- 2214844 TI - Straddling tricuspid valve. PMID- 2214845 TI - Electrocautery for parenchyma-sparing pulmonary resection: fast and easy. PMID- 2214846 TI - Volvulus of the intrathoracic stomach after total esophagectomy. PMID- 2214847 TI - [Subpopulations of immunocompetent cells in the placenta in normal pregnancy and in EPH gestosis]. AB - An effort of cellular element investigations in placentas of 8 physiological pregnancies and 7 EPH gestoses is performed with the aid of specific monoclonal antibodies by the indirect immunohistochemical method. The average mean of parturient ages (primiparae and pluriparae) was 24 years in EPH gestoses. By the aid of monoclonal antibodies OKT4, OKT8, OKT11, OKT6 and OKDR, Dako-macrophage, 2H4 (Coulter) murine type, immunocompetent cells were identified in the decidua, in the stroma of chorionic villi, in the intervillous space, and in the fibrinoid masses. The semiquantitative indirect method of the immunohistochemical cellular investigation was performed by the aid of optic microscopy in 20 fields per every cutting (section) of the placental tissue. The immunocompetent active cell distribution did not reveal any special difference in the frequency of placental tissues of physiogical pregnancies and EPH gestoses, but OKT11+ cells were present in the major number in gestoses (in decidua). OKT8+ and OKDR+ cells were found in a similar number in both populations, while OKT6+ were not found at all in any investigated tissue. PMID- 2214849 TI - [Bacterial flora in the reproductive system in the intra-amniotic infection syndrome]. AB - By the bacteriological aerobic analysis of the cervical swabs of 64 pregnant women with a subacute syndrome of intraamniotic infection in the 16th and 28th gestation weeks, pathogenic bacteria were isolated in 59 women (92.2%) and out of the swabs of 30 young girls with less sexual experience, 8 (26.7%) showed the presence of pathogenic bacteria, the difference being statistically highly significant (X2 V 56.9, p less than 0.001). From the ejaculates of the husbands of the same pregnant women, pathogenic bacterial were isolated in 57 of them (89.1%) and from the ejaculates of the controlled groups of young adolescents, pathogenic bacteria were isolated in 5 of them (16.7%), the difference being again statistically highly significant (X2 = 62.2, p less than 0.001). Comparing bacteria from the swabs of pregnant women with the syndrome of intraamniotic infection with those from the semen of their husbands, it has been found that the bacteria were identical in 40.6% if only one kind of bacteria was isolated and in 68.7% if several kinds of bacteria were isolated from the swab or ejaculates. In the group of 30 young girls a statistically significant dependence of pathogenic bacteria on the number of partners in their sexual life was observed (X2 = 4.54, p less than 0.05); pathogenic bacteria were isolated only once from the swabs of girls with only one partner and 6 times from the swabs of girls with two or more sexual partners. PMID- 2214848 TI - [Dysplasia and carcinoma in situ of the uterine cervix in pregnancy]. AB - During a 3-year period, 167 women with an abnormal cytological finding (112-IIIA, 41-IIIB and 14-IV) were followed up cytologically and colposcopically in six weeks' intervals. They were evaluated during pregnancy, vaginal delivery and the puerperal period, and the cytological findings showed no progression of intraepithelial lesions into the invasive ones. Definitive postpartum pathohistological findings in 53 patients showed that 32 had in situ carcinoma, 12 severe and 7 light dysplasias, and 2 benign changes. The possibility of the false negative cytological assessments or invasive cervical carcinoma was excluded. Patholhistological and cytological findings matched in 77% of cases, whereas the degree of the former was lower in 21% and higher in 2% of the patients. In as many as 40.7% of patients the first post-delivery control cytological finding was negative. The reversible nature of these findings is emphasized, as well as the need to follow up these patients for at least one year. PMID- 2214850 TI - [Fetal death in the 20th to the 36th week of pregnancy]. AB - In the period from 1986 to 1988, intrauterine fetal deaths from 20-36 weeks of gestation and 500 gm and more birth weight were analysed in a prospective study from the clinical and pathomorphological point of view. There were 57 such fetal deaths or 7.96% of the total number of 716 births till the 36th week of gestation, while 42.4% of women with the intrauterine fetal loss were cigarette smokers during pregnancy vs. 29.1% of such women among all those who gave birth during the same period. Smokers faced a relative risk of 1.8 for the fetal loss between the 20th and the 36th week of gestation. From the clinical standpoint, the cause of death was presumed in 40 or 71.4% of cases, while only in 24 or 42.1% of autopsies could the pathomorphological disorder be considered the cause of the intrauterine death. In 47 or 82.5% of cases, the observed pathomorphological disorders of the placenta, fetal membranes or the umbilical cord could also have contributed to the fetal death. Most often, i.e. in 20 or 35.1% of cases, chorioamnionitis was diagnosed and in 13 (22.3%) cases disorders of the placental circulation. In 7 cases (12.3%) neither clinical nor pathomorphological potential cause of death could be found. From the health care point of view it is important to find out those risk factors of fetal mortality which are preventable. Smoking during pregnancy could be the most preventable risk factor of fetal death. PMID- 2214852 TI - [Development of mechanisms for evaluation of the quality of perinatal care]. AB - Published evidence of the actual efforts for the development of mechanism for the quality assessment and assurance of perinatal care in the USA, Belgium, Netherlands and West Germany is presented. The choice of countries was determined by the availability of evidence. Despite known differences in the health care systems, every country developing mechanisms for the quality assessment in a particular field of health care involves in this process its respective professional associations. In the case of perinatal care it is the association of gynecologists and obstetricians. The administration of the process lies within the JCAH in the US and the ministries of health and universities in other countries. PMID- 2214851 TI - [Prevention of thromboembolic disease in gynecologic surgery]. AB - The authors present the results of their blind prospective comparative study of the postoperative thromboembolic protection of 490 gynecologic patients. Among them 250 (51%) were protected by a low dose heparin (LDH) subcutaneously in 12 hour intervals, 240 (49%) received heparindihydergot (HDHE). Thromboembolisms diagnosed by the 125J fibrinogen uptake test appeared in 26 (10.4%) patients protected by LDH and 23 (9.6%) by HDHE. The most frequent risk factors in patients with thromboembolisms were malignant diseases, obesity, varicose veins, hypertension and a history of deep vein thrombosis or pulmonary embolism. Haemorrhages appeared in 7 (2.8%) patients protected by LDH and 8 (3.3%) by HDHE. PMID- 2214853 TI - [HIV infection and human reproduction]. AB - Problems connected with HIV infection, especially with its transmission, problems of HIV infection as an indicator of the termination of pregnancy, the role of pregnancy in the activation of latent HIV infection, and the possibility of the transmission of HIV infection by breast feeding are put forward and discussed. The authors present the results of their own studies of the presence of HIV antigen in the genital secretion, fetal tissue, and amniotic fluid in 4 anti-HIV positive pregnant women, in whom pregnancy was interrupted because of HIV infection. HIV antigen was positive in the cervical secretion and fetal tissue of one of the four pregnant women, whose diagnosis was ab. imminens. The presence of HIV virus, probably also of HIV antigen, in the cervical secretion appears significant for the transmission of infection from mother to child and for the occurrence of spontaneous abortion. When it is not possible to apply the method of HIV virus isolation, the determination of HIV antigen could have a prognostic importance of the effect of HIV on the course and outcome of pregnancy. PMID- 2214854 TI - [The amazing neonate]. AB - According to a questionnaire including 78 general practitioners, specialists in pediatrics and obstetrics, physicians specializing pediatrics and obstetrics, and 43 students of a High Nursing School, 21.8% of physicians and 58% of nurses think that the newborn does not see, 17.9% of physicians and 18.6% of nurses think that the newborn does not hear, and 44.9% of physicians and 79.1% of nurses think that the newborn has no feeling of the position of the body in space and of its movements. The existence of the sense of smell in the newborn is denied by 66.7% of physicians and 55.8% of nurses, and of the sense of taste by 44.9% of physicians and 41.9% of nurses. All the nurses know that the newborn has the sense of touch, while 3.8% of physicians think the opposite. Two thirds of those included in the questionnaire think that the newborn can memorize and the three quarters of them think it can learn. Much fewer nurses than physicians (32.4%:61%) consider the newborn a passive receiver of external stimuli. As many as 97% of physicians think that an early stimulation of the newborn helps its psychomotor development and a high percentage of them positively assess the majority of measures implementing it. Yet, only 66.7% of physicians consider it necessary for parents to be near the hospitalized premature infant, while 24.4% of all the questioned do not consider the prevention of the birth of undesirable children a measure by which the quality of the parent-child relation could be influenced. PMID- 2214855 TI - [Time factors and trends in the onset of the menarche, sex maturation and experience of orgasm in a questionnaire administered to 971 women in Vojvodina]. AB - A questionnaire and interview of 971 women aged 15-80 years or more from three Voivodina communes (Becej, Veternik, Mali Idos) have supplied the following information: the arithmetic mean of the age of women during menarche is 13.459 +/ 1.523 years, the median being 13.872 years. Menarche appears earlier in the town (13.334 +/- 1.373) than in villages (13.668 +/- 1.61). The arithmetic mean of menarche recedes towards younger age groups (y = 12.90 +/- 0.106; r = 0.890, p less than 0.01), so that below 20 years is 1.4 years, and this is more pronounced in the town than on villages. The arithmetic mean of the age of women at sexarche (the first sexual intercourse) is 19.088 +/- 2.495 years, and the median is 18.964. The interval between the arithmetic mean of menarche and sexarche is 5.6 years, smaller in the urban (5.0) than in the rural environment (6.4). Sexarche recedes towards younger age groups (y = 18.136 +/- 0.130; r = 0.540), more intensively than the acceleration of menarche. In the course of their sexual life, 16.4% of women rarely experienced orgasm, 11.2% never did. The experience of orgasm "rarely" or "never" is statistically significantly more frequent in women over 40 years of life in relation to younger women (X2 = 6.893, p less than 0.01). PMID- 2214856 TI - [Brenner's tumor of the ovary]. AB - A retrograde analysis of surgically treated women for ovarian tumours in the last 20 years was performed. Out of a total of 1741 such patients, only 4 developed Brenner tumour (0.23%). Three of them were in the fifth decade and one in the eighth decade of life. All these four tumours were unilateral. Three of them were benign and one "proliferating". One patient had a mucinous cystadenoma in the other ovary and one a malignant cystadenocarcinoma in the same ovary with the benign Brenner tumour. Two patients had an atrophic endometrium and two had adenomatoid, i.e. atypical hyperplasia. The size of tumours varied from 2 to 20 cm in diameter. PMID- 2214857 TI - [Preoperative administration of dinoprost gel for termination of early pregnancy in primigravidas]. AB - A total of 60 primigravid women due to undergo early pregnancy termination (6.5 to 10 weeks) were randomly selected for the intracervical application of 0.5 mg dinoprostone in the form of intracervical gel (Prepidil gel, Upjohn). The gel was inserted 6 hours prior to vacuum aspiration. Before application all women had the cervix closed, i.e. dilated less than Hegar #3. After 6 hours there was noticed a marked cervical softening and dilatation (mean 9.28 mm) in all 60 cases (100%). Twelve (20%) women needed an additional mechanical dilatation which was performed very easily and atraumatically. An incomplete abortion occurred in 14 (23.33%) cases; 35 (58.33%) women had uterine cramps, and in 28 (46.66%) gastrointestinal side effects were recorded. There were no significant changes in the blood pressure or body temperature. During the procedure there were no complications. PMID- 2214858 TI - [Bacteriological analysis of the cervical canal in uterine cervix insufficiency]. AB - A bacteriological analysis was made of pyogenic agents from the cervical canal of 260 pregnant women with cervical incompetency, in whom the cerclage of the cervix was performed. Pyogenic agents were found in 139 (53.5%) pregnancies. The most frequently isolated pathogenic agent was Enterococcus--in 19.2% of all pregnant women and in 36.0% in those with a pathologic swab. E. coli was isolated in 16.5% of all pregnant women and in 30.9% of those with the pathologic swab. A significantly higher number of pathologic swabs were found in women with colpitis and the cleanliness 3 degree of the vaginal discharge and without colpitis (6.4%). In pregnant women with a pathologic swab, in spite of the cervical cerclage, spontaneous abortions and premature deliveries were significantly more frequent (8.2% and 16.4% respectively) than in pregnant women with a sterile swab (1.8% and 6.1% respectively). PMID- 2214859 TI - [Intracerebral hemorrhage in a grand multipara with EPH gestosis]. AB - A 43-year-old multiparous woman (ninth childbirth) with the EPH-gestosis not observed during pregnancy, first came to the hospital in the 40th week of gestation due to the rupture of membranes and weak labor pains. Having lain down in the delivery room, the patient immediately lapsed into a coma and developed hemiplegia on the right side of the body. Suspecting a cerebrovascular insult caused by hypertension within the pre-existing EPH-gestosis, the C-section was performed in the best interest of both mother and child. Following the operation, the CT of the brain showed massive intracerebral and intraventricular hemorrhage. The patient was moved to the Intensive Care Unit, where she died six days after the insult. PMID- 2214860 TI - [Dr. Lazar Nenadovic, gynecologist-obstetrician and founder of balneology and physical medicine in Serbia]. AB - Prof. Dr. Lazar-Laza Nenadovic specialist in obstetrics and gynaecology (Modos, 1870--Beograd, 1939), the founder of advanced physical medicine and balneo climatology in Serbia. Prof. Nenadovic, besides a series of papers on obstetrics and gynaecology, is the author of a monograph on obstetrics and gynaecology published in Novi Sad in 1912, being the first of this kind in Serbia. Its title is Diseases of the female, their origin, causes and treatment. He was also one of the pioneers of gynecologic balneology in Yugoslavia and one of the founders of the Belgrade School of Obstetrics and Gynaecology, as well as a close collaborator and friend of Prof. Dr Milos Bogdanovic, the first head and professor of the Department of Obstetrics and Gynaecology of the School of Medicine in Belgrade. PMID- 2214861 TI - [Validity of the direct immunofluorescent monoclonal antibody test in the diagnosis of chlamydial infection]. AB - The sensitivity and specificity of direct fluorescent monoclonal antibody staining were compared with the isolation of the organisms in McCoy cells. For both diagnostic methods cervical smears were taken in 120 women. Of 120 women 25 (20.8%) were infertile, 60 (50.0%) healthy fertile women and 35 (29.8%) adolescents who came for control gynecological examination. C. trachomatis was isolated in 5/25 (20.0%) of infertile women, in 5/60 (8.3%) of healthy fertile women and in 4/35 (11.4%) adolescents. With the cell culture as the reference method, the antigen detection test had a sensitivity of 92.8%, a specificity of 98.1%, a positive predictive value of 86.7% and a negative predictive value of 99.1%. PMID- 2214862 TI - Department of Health and Hospital's final regulations on infectious waste. PMID- 2214863 TI - A recruitment and marketing plan for Louisiana State University School of Dentistry. PMID- 2214864 TI - Virus dissemination via the lymphomyeloid complex. AB - In the previous AIDS symposium organized by the Society, Witte and Witte (1) made a number of predictions, one of which was that in AIDS patients, "Lymph from the thoracic duct should be strongly positive for HIV." Though direct evidence for this is lacking, some early experiments of ours with vaccinia virus (2) are fully in accord with this prediction, to which they lend indirect support. In rabbits, nasally instilled vaccinia virus spreads via the lymphatic pathway (afferent peripheral lymph--deep cervical gland--efferent lymph--thoracic duct) in as short a time as nine hours. Virus is transported mainly in cells, for when the efferent lymph is centrifuged virus is found only in the cell sediment. It seems reasonable to assume that other viruses, including HIV, are similarly disseminated. Paradoxically, the lymphomyeloid complex both greatly facilitates the spread of virus, and at the same time, mounts the immunological defenses against the virus which it so effectively helps to disseminate. Whatever the portal of entry of the virus, its transport by migrating cells ensures its dissemination throughout the lymphomyeloid complex, including the bone marrow. The bone marrow is an integral part of the complex, as the prime source of B lymphocytes, T lymphocyte precursors, and many of the antigen-presenting cells as well as the granulocytes. There is some evidence concerning possible ways in which the bone marrow can contribute to the development of immune deficiency in AIDS patients. The bone marrow merits further study in this context. PMID- 2214865 TI - The relevance of lymphoid cell migration to immunodeficiency syndromes. AB - It has been known for some time that antigen stimulation can alter lymphocyte traffic patterns and that viruses are particularly potent in this respect; such alterations may be a consequence of host-derived factors. The retention of lymphocytes in lymph nodes can be sustained for several hours with locally administered interferon (IFN)alpha. The extravasation of lymphocytes from blood into non-lymphoid tissues can be induced in the skin with IFN gamma and particularly tumor necrosis factor (TNF)alpha. Recent evidence supports the concept that the migratory capacity of CD4+ cells differs from the capacity of CD8+ cells. Agents (cytokines?) which differentially affect the traffic of these two sub-sets have not yet been described but such a possibility has not been adequately tested. Several new molecules have been defined which alter the interactions between lymphocytes and blood vascular endothelial cells, and these may be important in the critical adhesive event in lymphocyte traffic. In both rat and sheep, it has been possible to cultivate post-capillary endothelial cells from lymphoid tissue, and this may be a helpful approach to studying the mechanisms and molecules involved in adhesion. New cell tracking dyes recently available (Zynaxis Cell Science) permit more significant, long-term studies on the life span of lymphocyte sub-sets and their migratory status. In our experiments, labeled lymphocytes can be followed in vivo for over 30 days. Traffic alterations may explain some of the abnormalities in immunodeficiency states. PMID- 2214866 TI - AIDS, Kaposi sarcoma, and the lymphatic system: update and reflections. AB - Based on ongoing basic and clinical investigations, further evidence is presented that the AIDS-Kaposi sarcoma (AIDS-KS) complex involves a progressive disturbance of the blood-lymph circulatory loop of fluid, macromolecules, and migrating cells. We first surveyed the spectrum of vascular abnormalities including Kaposi sarcoma (KS) found in the AIDS/ARC population, then non-invasively imaged lymphatic system abnormalities in AIDS-KS by whole body lymphangioscintigraphy, and finally examined the biologic behavior of AIDS-KS cells in long-term tissue culture. These observations are viewed in terms of the lymphatic and blood vascular route of entry and transport of free and cell-associated virus and other opportunistic pathogens as well as poorly understood host endothelial-immune system interactions. PMID- 2214867 TI - Grip and stick and the lymphatics. AB - Kaposi sarcoma is a common, though not inevitable consequence of AIDS. There is a body of opinion that believes that this sarcoma is derived from lymphatic endothelium, or at least from a failure of vascular endothelium to distinguish between whether it is attempting to be a blood vessel or a lymphatic. While immunodeficiency and its consequences have proved to be the most significant area of research, the general biology of endothelium, and especially angiogenesis, has perhaps been neglected. I predict that the most important new concept in the biology of endothelium is the recognition of mechanico-receptors as a determinant of its behavior. The concept is illustrated by articles from Oxford (Ryan 1989), from Boston, Massachusetts (Ingber & Folkman 1989), and from Moscow (Shirinsky et al 1989). Most authors studying endothelium have concentrated on blood vascular endothelium and ignored the rich lymphatic bed. Since the lymphatic is par excellence a mechanical receptor, this is perhaps surprising. The lymphatic functions by its responsiveness to mechanical forces, it is a fine control for hydrostatic pressure within the interstitium, and morphologically, its flat and attenuated endothelium linked to strong anchoring fibers is biologically exactly the kind of behavior required of a cell that is responsive to mechanical factors. Perhaps the best known mechanical receptor is the stretch receptor in the muscle fiber. The linkage of this receptor to the enzyme protein kinase C has been described. Ryan has also pointed out that protein kinase C may be an important mechanico-receptor in the fibroblast and possibly also universally in all cells, including lymphatic endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2214868 TI - Development of immunomodulators for treatment of HIV infection. AB - Although considerable attention has been devoted to development of antiviral drugs for therapy of HIV infection, relatively little priority has been directed to correction of the progressive immunologic defect that develops in these patients. We described the development of the therapeutic effect of an immunosupportive biological agent (IMREG-1) derived from human leukocytes. Specifically, IMREG-1 reduced the risk of progression from advanced AIDS-related complex (ARC) based on a randomized double-blinded control trial over a six month period of the laboratory and clinical parameters predictive of a high risk of progression from ARC to AIDS. The comparative value of CD4+ cell numbers, anergy to recall antigens and symptomatology in assessing risk of progression were also examined. PMID- 2214869 TI - High resolution magnetic resonance spectroscopy in clinical biology. PMID- 2214870 TI - In vivo recruitment of GM-CSF-response myelopoietic progenitor cells by interleukin-3 in aplastic anemia. AB - Previous studies have indicated that colony-stimulating factors may stimulate myelopoiesis and thus increase the number of circulating white blood cells in patients with hematopoietic failure including aplastic anemia. However, long-term administration of the factor was required to maintain its response. In the present article we report on a patient with severe aplastic anemia undergoing treatment with recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF). After an initial response, the patient became refractory to GM CSF. However, treatment with interleukin (IL)-3 restored responsiveness to GM CSF, suggesting that IL-3 may have replenished the bone marrow with myelopoietic progenitor cells sensitive to the action of GM-CSF. This observation suggests the value of application of sequentially acting hematopoietic growth factors in aplastic anemia patients. PMID- 2214871 TI - c-fms expression in acute leukemias with complex phenotypes. AB - The c-fms proto-oncogene product, which is the receptor for the macrophage colony stimulating factor CSF-1, is always found expressed in acute myeloid leukemia cells, irrespective of their stage of differentiation according to the FAB classification (Dubreuil P, Torres H, Courcoul M, Birg F, Mannoni P. Blood 1988;72:1081-1085). We have extended this study and looked for c-fms expression in poorly differentiated myeloid leukemias, in a series of acute leukemias of either T or B origin and in biphenotypic leukemias. We now report that expression of c-fms is still related to the myeloid origin of the leukemic proliferation, but that it can also be found in some acute leukemias presenting clonal rearrangements of the T cell receptor gene. Thus expression of the c-fms/CSF-1 receptor may not be exclusively a marker for myeloid proliferations. PMID- 2214872 TI - First intron and M-bcr breakpoints are restricted to the lymphoid lineage in Philadelphia positive acute lymphoblastic leukemia. AB - Knowledge of the level of commitment of the target cell in hematological malignancies may have important therapeutic and prognostic implications. Cell lineage involvement was investigated in two cases presenting with acute lymphoblastic leukemia diagnosed on clinical and immunological findings and having the Philadelphia translocation t(9;22)(q34;q11). DNA from cells separated into mononuclear (lymphoid) and granulocytic fractions was hybridized with Philadelphia breakpoint-specific probes. This revealed that the breakpoint giving rise to the Philadelphia chromosome in case 1 was within the major breakpoint cluster region and in case 2 was in the first intron of the BCR gene. Rearrangement was found in the lymphoid but not the granulocyte fraction in each case. It is therefore concluded that the target cell for chromosomal change in these cases was a lymphoid committed progenitor cell, irrespective of breakpoint location. PMID- 2214873 TI - Association of protein tyrosine phosphorylation with B cell differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). AB - We have assessed whether tyrosine protein kinase (TPK) is involved in B cell differentiation. In vitro phosphorylation of an endogenous substrate in B cell leukemias showed that leukemic B cells at different stages of differentiation had specific endogenous substrates in tyrosine phosphorylation as well as distinct TPK activity. To clarify the relationship between TPK and the process of B cell differentiation, we studied protein tyrosine phosphorylation in two kinds of leukemic B cells, which showed distinct responses to TPA (12-O tetradecanoylphorbol-13-acetate) in B cell differentiation. TPA-treated leukemic B cells from patients with B cell chronic lymphocytic leukemia (B-CLL) differentiated into cytoplasmic immunoglobulin (clg)+ plasmacytoid cells, while TPA-treated leukemic B cells from patients with hairy cell leukemia (HCL) did not differentiate into clg+ cells, but showed a peculiar morphological change, spreading. Untreated B-CLL cells and HCL cells showed similar TPK activities and tyrosine protein phosphorylation. When treated with TPA, enhanced phosphorylation was seen in B-CLL cells, while a clear reduction in phosphorylation was found in HCL cells. However, using 4-hydroxycinnamide derivatives which reduce TPK activity, we found that only the reduction of TPK activity did not lead HCL cells to spreading. These data suggest that protein tyrosine phosphorylation and/or dephosphorylation might be involved in B cell differentiation, but only the change of TPK activity in HCL cells is not sufficient to induce effects. PMID- 2214875 TI - Trisomy 8 in acute lymphoblastic leukemia (ALL): a case report and update of the literature. AB - A case of acute lymphoblastic leukemia (ALL) cytogenetically characterized by trisomy 8 as a sole aberration is described. The patient, one of 116 adults with ALL investigated cytogenetically, was a 36-year-old male with leukocyte count 12.3 x 10(9)/liter with 90% blasts of FAB type L1 and common ALL immunological phenotype. Remission was achieved with the current U.K. treatment trial. The patient recovered from an autologous bone marrow transplant (BMT) in first remission but relapsed 15 months later. BMT, in second remission, from an unrelated donor, was rejected. Autologous reinfusion failed and he died 26 months after diagnosis. Molecular investigation of immunoglobulin gene rearrangement identified the same B cell clone at diagnosis and in relapse. The clinical and cytogenetic findings of six published cases of ALL with trisomy 8 have been reviewed with updates supplied by the authors. These reveal an heterogeneous group of patients ranging in age from 9 months to 39 years with no apparent association with a particular immunophenotype. Four patients were alive after 10 108 months follow-up. Two patients died, in relapse, 7 and 17 months after diagnosis. Thus trisomy 8 occurs in ALL with an incidence of 1-2%. The prognostic significance of this remains to be determined. PMID- 2214874 TI - Early and long term follow-up with minisatellite probes in bone marrow transplanted patients. AB - Twenty-five patients who received bone marrow transplantation (BMT) for chronic granulocytic leukemia (CGL), acute leukemia and severe aplastic anemia were studied before and after BMT in order to document and characterize the events following transplantation. DNA analysis was performed using minisatellite probes, which give rise to extremely polymorphic Southern blot band patterns specific to each individual and are regarded as "genetic fingerprint." Sensitivity studies using a mixture of donor and recipient cells could distinguish the presence of 1% of cells from one individual. Blood specimens were obtained from donor recipient before BMT and at days 10, 30, 90, and 270 after BMT. Karyotype analysis was also performed in CGL patients at the same time of DNA analysis. Engraftment was identified by DNA analysis as early as 10 days posttransplant and correlated with cytogenetic findings. This confirmed that a single hybridization filter is informative in 100% of patients and is easily applicable for early and long term studies of chimerism in BM transplanted patients. PMID- 2214876 TI - Pleural involvement in hairy cell leukemia--development under alpha-interferon and remission upon pentostatin therapy. PMID- 2214877 TI - Mayo and the antigravity suit. PMID- 2214879 TI - Rehabilitative techniques for athletes after reconstruction of the anterior cruciate ligament. AB - A wide spectrum of protocols is available for rehabilitation after anterior cruciate ligament reconstruction, and little agreement exists on the specifics of strengthening exercises or the sequence of activities. In this article, we discuss the current rehabilitative techniques used at the Mayo Clinic for athletes who have undergone anterior cruciate ligament reconstruction. These techniques are based on established principles of rehabilitation, clinical experience, and new information about the related biomechanics of the knee. An illustrative case reflects the benefits of this rehabilitation program, which lasts up to 1 year and is divided into five stages. The early stages focus on protected mobilization and a strengthening program that emphasizes closed rather than open kinetic chain exercises. Later, neuromuscular-proprioceptive training and sport-specific agility training redevelop the reaction time and the "coordination engrams" necessary for athletic competition. High-quality surgical care and a closely supervised rehabilitation program, based on kinesiologic and biomechanical factors as they pertain to the anterior cruciate ligament, are necessary for a successful outcome. PMID- 2214878 TI - Cutaneous malignant melanoma in Rochester, Minnesota: trends in incidence and survivorship, 1950 through 1985. AB - In Rochester, Minnesota, 107 incidence cases of cutaneous malignant melanoma (in 46 male and 61 female patients) were diagnosed during the years 1950 through 1985. Overall crude incidence rates were 6.0 and 6.6 per 100,000 males and females, respectively. Evaluation of trends in 9-year periods showed that the rates increased from 3.2 to 8.9 for males (P = 0.015) and from 4.4 to 11.7 for females (P less than 0.001). Age-specific rates suggested that the highest incidence occurs in the age-groups 50 to 59 years and 70 years or older for males and 40 to 49 years and 70 years or older for females. Lesions were most common in the head and neck area among males (P = 0.044) and on the lower extremities among females (P = 0.018). The most frequent histologic type was superficial spreading melanoma (61%). Five-year survival was diminished overall for patients with cutaneous malignant melanoma--0.72 in comparison with 0.88 expected for the general population. Statistically significant risk factors for survival were depth of invasion of the lesion (Clark level), thickness of the lesion, histologic type, and age of the patient. PMID- 2214880 TI - Long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B: a prospective, randomized treatment trial. AB - We conducted a prospective, randomized trial to study the efficacy and tolerance of long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B. Ten patients were randomly assigned to a 6 month interferon regimen, and 10 patients were assigned to a 3-week interferon trial. Eleven patients (five assigned to long-term treatment and six to short term treatment) did not complete interferon therapy: eight had either severe thrombocytopenia or neutropenia; one had pronounced fatigue in relationship to administration of interferon; one had spontaneous bacterial peritonitis and sepsis and died; and one had a massive fatal variceal hemorrhage during interferon therapy. Most of the serious hematologic complications occurred in patients with cirrhosis and hypersplenism. In one patient, seroconversion to hepatitis B virus DNA negativity occurred before the onset of treatment. Four of the five patients able to complete the 6-month interferon regimen and only one of four patients able to complete the 3-week trial had seroconversion to hepatitis B virus DNA negativity. Thus, we conclude that the therapeutic response was better among patients who were able to complete a 6-month interferon trial. In patients with cirrhosis and hypersplenism, development of either severe thrombocytopenia or leukopenia associated with interferon therapy precluded completion of treatment. PMID- 2214881 TI - Fast computed tomography for quantitative cardiac analysis--state of the art and future perspectives. AB - Two fast computed tomographic scanners, designed primarily for imaging cardiac structures and function, have been in use since the early 1980s. The technical aspects of both systems have been described previously in detail, and a considerable body of scientific literature now documents the biomedical capabilities of these scanners. This review examines these biomedical capabilities as applied to quantitative analysis of the heart and pulmonary circulations. On the basis of this overview, some speculations about the current strengths and possible further developments of the fast computed tomographic approach in these applications are made. PMID- 2214882 TI - Transcranial Doppler ultrasonography: clinical applications in cerebrovascular disease. AB - Transcranial Doppler ultrasonography was introduced in 1982 as a noninvasive procedure for assessment of the intracranial cerebral circulation. The lightweight and portable equipment used for transcranial Doppler examination facilitates its use in the bedside assessment of critically ill hospitalized patients and outpatients. Clinical applications include the diagnosis of vasospasm in patients with subarachnoid hemorrhage, assessment of intracranial collateral flow in patients with extracranial arterial occlusive disease, detection of intracranial arterial stenosis, identification of the feeding arteries of arteriovenous malformations and monitoring the hemodynamic effects of their treatment, confirmation of the clinical diagnosis of brain death, intensive care unit monitoring of brain-injured patients, and intraoperative and postoperative monitoring of neurosurgical patients. Transcranial Doppler technology is also providing new insights into the pathophysiologic mechanisms of a variety of cerebrovascular conditions. Clinicians will find transcranial Doppler technology most helpful if they have a specific question about the status of the intracranial circulation. Further investigations may expand the clinical and research utility of this technology. PMID- 2214883 TI - Unsuspected syphilitic hepatitis in a patient with low-grade proteinuria and abnormal liver function. AB - A 25-year-old patient was found to have cholestatic liver enzyme abnormalities during assessment for asymptomatic low-grade proteinuria at the US Naval Hospital in Portsmouth, Virginia. These abnormalities persisted for a 6-month period, and an extensive workup, including viral serologic studies, rapid plasma reagin test, iron studies, ceruloplasmin, antimitochondrial, antinuclear, and anti-human immunodeficiency virus antibodies, endoscopic retrograde cholangiopancreatography, and liver biopsy, was unrevealing until serologic tests for syphilis were repeated to evaluate a new onset of urethral discharge. The patient had none of the more characteristic signs of secondary syphilis. The liver enzyme abnormalities rapidly resolved after treatment with penicillin. Syphilis remains the great impostor and still must be considered in the differential diagnosis of unexplained liver enzyme abnormalities, even in a patient with no symptoms or signs of early syphilis. PMID- 2214884 TI - The melanoma epidemic thus far. PMID- 2214885 TI - Benedykt Dybowski--physician, explorer, scientist, political prisoner. PMID- 2214886 TI - Is the nurse practitioner in? A day in the life of. PMID- 2214887 TI - Noise and hearing loss. PMID- 2214888 TI - A school nurse in Moscow. PMID- 2214889 TI - Age-dependent changes of the sympathetic innervation of the rat kidney. AB - The influence of aging on the sympathetic innervation of the kidney was studied in 3- (considered to be young), 12- (considered to be adult) and 24- (considered to be old) month-old male Sprague-Dawley rats by means of high pressure liquid chromatography with electrochemical detection, catecholamine histofluorescence and acetylcholinesterase (AChE) histochemistry. Body and kidney weights were significantly increased in adult in comparison with young rats. No further increase of either body or kidney weight was appreciated in old rats. Noradrenaline levels were increased by about 48% in adult rats and were decreased in old rats (by approx. 22% vs. young and 60% vs. adult). The density of perivascular noradrenergic fibres was significantly increased in adult rats and decreased in old animals. The percentage of kidney glomeruli supplied by AChE positive nerve fibres is also remarkably increased in 12-month old rats and decreased in 24-month-old rats. The present data indicate that there is a striking increase in the expression of sympathetic innervation of rat kidney at 12 months of age followed by a significant decrease in the expression of innervation in old age. These changes are discussed in relation to the age dependent impairment of renal function. PMID- 2214890 TI - Hypoxia and pharmacological treatment in differently aged rats: effect on muscular metabolite concentrations. AB - Metabolite concentrations in gastrocnemius and soleus muscles were compared in young-adult (4 months), mature (12 months) and senescent (24 months) rats after continuous (72 consecutive hours) exposure to normobaric hypoxia or normoxia with the intraperitoneal administration of the vasodilator naftidrofuryl or saline solution for 30 days consecutively before hypoxia. The following metabolites were assessed in gastrocnemius muscle in relation to: (a) energy mediators: ATP, ADP, AMP; (b) energy store: creatine phosphate; (c) anaerobic glycolysis: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate; (d) Krebs' cycle: citrate, alpha ketoglutarate, malate; (e) free amino acids related to Krebs' cycle: aspartate, glutamate, alanine; and (f) ammonia. In the soleus muscle only ATP, creatine phosphate, glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, citrate, alpha-ketoglutarate malate, aspartate and glutamate were assessed. Aging does not seem to affect soleus and gastrocnemius muscles in the same way. Some gastrocnemius muscle metabolites show linear changes in their concentrations with aging, while for the soleus muscle the only linear change relates to glucose 6 phosphate. As regards the influence of hypoxia on muscular metabolism, all the most important changes observed in metabolite concentrations in comparison with control values take place at the age of 4 and 24 months. Furthermore, as regards naftidrofuryl action, the most important variations observed concern only 4-month old animals. Finally our data show that only in certain cases has pharmacological treatment been able to modify the influence of hypoxic conditions on the concentration of muscle metabolites, regardless of the age of the animals. PMID- 2214891 TI - Protein secretion by rat submandibular glands in response to isoproterenol, alpha methylnoradrenaline and clonidine during aging. AB - Changes in salivary volumes and the three types of proteins secreted by the submandibular salivary gland (SMG) of male rats at 3.5, 5.5, 8, 12, 13, 14, 15, 19, 21 and 24 months of age in response to the beta 1-, alpha 1- and alpha 2 adrenoceptor agonists, isoproterenol (IPR), alpha-methylnoradrenaline (alpha-mNA) and clonidine (Clonid), were studied and compared by measuring the weight and by isoelectric focusing electrophoresis with the Phast System on both the gradient pH 3.5-5 and 3.5-9 gels with silver staining. A protein (protein A, tentatively termed in this study) purified by FPLC from saliva elicited by IPR was also analyzed by SDS-polyacrylamide gel electrophoresis, the immuno-thermoblotting method, carbohydrate determination and neuraminidase treatment. Unexpected findings were observed that salivary volumes, but not the protein concentration, were substantially increased by Clonid-, but not IPR-, stimulation with ages up to 24 months of age and that the three types of proteins elicited by each agonist were different during aging. The gamma-type of proteins elicited by Clonid was not greatly changed during aging, whereas several proteins at about neutral pI in the alpha-type, elicited by alpha-mNA, at 5.5 to 21 months of age and a protein A in the beta-type, elicited by IPR, at 13 to 24 months of age were greatly increased. This protein A without any carbohydrate and sialic acid, located only in the acinar cells, but not in any duct system, had a molecular weight of 16,000 and a pI of 4.05. We conclude that the secretory function of the SMG in the aged animals is in general little changed. PMID- 2214892 TI - Longitudinal Gompertzian analysis of adult mortality in the U.S., 1900-1986. AB - Analysis of mortality data for the United States from 1900 through 1986 demonstrates near perfect Gompertzian mortality rate distributions for adult American men and women. In the U.S. between 1900 and 1986, annual age-adjusted mortality rate distributions were determined by a fixed common intersect point (for men, the mortality rate at age 87.41 years was 18,810/100,000; for women, the extrapolated mortality rate at age 108.69 years was 75,365/100,000) and a variable environmental factor. Despite living in the same environment, the environmental factor contributing to adult mortality is at present significantly less for women than men. However, analysis predicts that in an environment less conducive to human survival than has existed in the United States during this century, the environmental factor contributing to adult mortality was less for men than women. The study further implies that as the environment becomes more favorable for human survival, men will experience an effective lowering of their theoretical maximal life span toward a limit of 87.4 years. The calculated maximal life span for men has already decreased 7 years during this century. This negative effect of a more favorable environment also occurs in women, although the theoretical maximal life span in women is lowered only toward a limit of 108.7 years. PMID- 2214894 TI - Clonal lifespans cultured in chemically defined medium and conventional bacterized medium in Paramecium octoaurelia. AB - The unicellular ciliate, paramecium, reproduces by binary fission, but can not continue to divide unlimitedly without sexual reproduction. We examined the clonal life span of Paramecium octaurelia stock 299 cultured in conventional bacterized medium (BM) and a chemically defined medium (DM). The cells that lived in BM divided 300 times. Although the cells in DM divided more slowly, some cells continued to divide more than 100 times. The mean life span of 90 cell lines cultured in BM was 151 +/- 49 fissions and that of 84 cell lines in DM was 68 +/- 28. When some older cells, which had been cultured in DM, were transferred to BM, most of them showed much longer life spans than those remaining in DM. The results showed that the life spans of cell clones were affected by the culture conditions. PMID- 2214893 TI - Ageing of procaryotes. Acholeplasma laidlawii as an object for cell ageing studies: a brief note. AB - It was established that A. laidlawii cell viability in the stationary phase of culture development decreases according to the Gompertz law. It was shown that the "stationary" ageing of A. laidlawii cells is accompanied by the lower intensity of phosphorus-containing compounds biosynthesis, decreased rate of membrane proteins synthesis and degradation and also by accumulation of DNA single-strand breaks. The biochemical changes found in ageing A. laidlawii cells are similar to ageing manifestations of resting eucaryotic cells. According to the authors opinion, the received data show that the A. laidlawii cell culture may be used as an object for investigation of the cell ageing mechanisms. PMID- 2214895 TI - Patient judgements of hospital quality. Report of a pilot study. PMID- 2214896 TI - Patient judgments of hospital quality. A taxonomy. PMID- 2214897 TI - Patient judgments of hospital quality. Pilot study methods. Design of study. PMID- 2214898 TI - The Patient Judgments of Hospital Quality (PJHQ) Questionnaire. PMID- 2214900 TI - The PJHQ questionnaire. Exploratory factor analysis and empirical scale construction. PMID- 2214899 TI - Patient judgments of hospital quality. Response to questionnaire. PMID- 2214901 TI - Further evaluations of the PJHQ scales. PMID- 2214902 TI - Patient evaluations of hospital care. A review of the literature. PMID- 2214903 TI - Patient judgments of hospital quality. Conclusions and recommendations. PMID- 2214904 TI - [Prevalence of nosocomial infections in Catalonia. II. Microorganisms and antimicrobial agents]. AB - In the prevalence study of infections carried out in 33 hospitals from Catalonia in 1988, where 7,434 patients were included, information about the responsible microorganisms and the prescribed antimicrobials was collected (in addition to the data on community and hospital infections and risk factors) and is reported in the present article. The microbiological diagnosis was made in 43% of hospital infections and in 31.9% of community infections. Gram negative organisms predominated (57.3% of isolates in hospital and 46.5% in community infections). The most prevalent organisms in hospital infections were Escherichia coli and Pseudomonas aeruginosa; the most common Gram positive organisms were Staphylococcus aureus and Streptococcus faecalis. 31.7% of the studied patients received antimicrobials. The health care area with the highest prevalence was Intensive Care (46.6%), and General Surgery had the lowest one (26.8%). There were no significant prevalence differences between the three types of hospitals depending on their size. The most commonly used antimicrobial was gentamicin. The empirical indication rate was remarkably high (58.6%), the rate of antimicrobials with a specific indication was low (16%), and the rate of use of prophylactic antimicrobials was high (25.4%). There also was a remarkable disparity and extension of the types of drugs used. PMID- 2214905 TI - [Features of Paget's disease of bone in a new high-prevalence focus]. AB - We report the features of a group of 41 patients with Paget's disease (PD) who were identified in a cross sectional study in the "Sierra de la Cabrera" (Madrid). As the screening test, we used serum alkaline phosphatase quantification, and the diagnosis was confirmed by radiological study. This biochemical parameter shows an excellent diagnostic performance, with a sensitivity of 98% and a specificity of 85%. The prevalence in the population over 40 years of age is 6.37% (95% CI 4.79-7.95) which, comparing it with that from other areas, suggests that this region is a "focus" of PD. 51% of cases had the characteristic symptoms of the disease, bone pain being the most common (44%). We compared the abnormalities in the patients with those of a control group with strictly comparable features, and we found that bone deformity (34%) and a localized increase in skin temperature (27%) were the most discriminative data, while cranial symptoms (26%) were nonspecific. Cataracts and actinic keratosis were associated with PD in the crude analysis (p less than or equal to 0.01). When age was controlled for, the statistical significance of cataracts disappeared, whereas that of actinic keratosis was maintained (odds ratio 4.08, p less than or equal to 0.01). A high family incidence was found, with 15 proven cases (36.5%) in 6 families. Apart from a marked increase in alkaline phosphatase (mean: 407 mU/ml), other abnormalities or biochemical differences with the control were not found. These results suggest an interaction of genetic and environmental factors, and is wholly consistent with the multifactorial etiological hypothesis of PD. PMID- 2214906 TI - [High incidence of ampicillin resistance in Salmonella spp non typhi]. AB - Salmonella spp non typhi is a common cause of gastroenteritis and, more rarely, extraintestinal infections in humans. The type of syndrome determines the choice and duration of antibiotic therapy. Extraintestinal infections by this organism require correct antibiotic therapy. In the present study, the susceptibility to antibiotics of 59 strains of Salmonella spp non typhi from clinical sources, isolated during a period of three and a half months, were evaluated. Fifty one of them were S. enteritidis, 7 S. typhimurium and 1 S. schwarzengrund. A high frequency (45.8%) of resistance to ampicillin (MIC greater than 256 micrograms/ml) was found. Other antibiotics had good or excellent in vitro activity: 90% of strains were sensitive to tetracyclines, 93% to chloramphenicol, 97% to co-trimoxazole, and 100% to cefotaxime and ciprofloxacine. It was concluded that the high frequency of ampicillin resistance to ampicillin precludes its use as first choice antibiotic in our area for suspected extraintestinal infections caused by Salmonella spp non typhi. PMID- 2214907 TI - [Epidemiology of type 1 diabetes mellitus. A way to its prevention?]. PMID- 2214908 TI - [Diving accidents. 2. Respiratory barotrauma: a pulmonary over-pressure syndrome]. PMID- 2214909 TI - [A 31-year-old woman with a tumor mass in the left leg]. PMID- 2214910 TI - [Morphological differences in the vascularization of tuberculoma and tuberculous brain abscess]. PMID- 2214911 TI - [Symptomatic hypomagnesemia in a patient treated with cisplatin]. PMID- 2214913 TI - [Neoplasms associated with chronic lymphatic leukemia]. PMID- 2214912 TI - [Secondary prevention of pneumocystis carinii pneumonia by intravenous pentamidine]. PMID- 2214914 TI - [Prevalence of infections and use of antimicrobial agents in a district hospital]. PMID- 2214915 TI - [Symmetrical peripheral arthritis as expression of multiorgan extrapulmonary tuberculosis]. PMID- 2214916 TI - HyperShell: an expert system shell in a hypermedia environment--application in medical audiology. AB - HyperShell is an expert system shell developed in a hypermedia environment. Several artificial intelligence techniques such as frames and semantic networks are used in an original interpretation to enhance the interaction between the user and the program. The typical navigation tools of hypermedia such as clickable buttons and text search are extended to the semantic structure of HyperShell, creating a set of new tools. Examples from a medical expert system (Audex HM) developed in HyperShell are described. PMID- 2214917 TI - Variables processing in expert system building: application to the aetiological diagnosis of infantile meningitis. AB - We describe a method for the analysis and quantitative synthesis of information in a clinical data file using as an example the aetiological diagnosis of infantile meningitis. The results obtained together with the qualitative knowledge of experts in the field have enabled an experimental system to be constructed. This is performing sufficiently well to be introduced into a hospital environment to assist young doctors facing an emergency situation. PMID- 2214918 TI - Detection of the B waves in the oscillation of intracranial pressure by fast Fourier transform. AB - Intracranial pressure (ICP) oscillation consists of a cardiac-induced component, a respiration-induced component and fluctuation of the base level of ICP. Lundberg reported three types of fluctuations of the base level of ICP with increasing ICP which were referred to as A, B and C waves. Computer algorithms for sampling, processing and displaying ICP data were investigated to depict the power spectrum of ICP oscillations by fast Fourier transform (FFT), thus enabling the B wave to be automatically detected. A power peak was found in the ICP power spectrum between 30 and 120 s, which corresponds to the frequency of the B wave. The maximum power, corresponding to the B-wave amplitude was above 0 dB. An appropriate sampling interval for FFT inputs was about 8 s for real-time processing of the ICP data. The mean ICP value was found useful for making the B wave peak clearer by reducing the cardiac and respiratory components of ICP oscillations; the window function had no effect on B-wave detection in the ICP power spectrum. PMID- 2214919 TI - Robust multivariate methods in laboratory techniques and in assisting medical diagnosis. AB - The usefulness of robust multivariate methods in medical applications, for example, the indirect estimation of total lung capacity by robust regression and the assistance of medical diagnosis in obstructive airways disease using robust discriminant functions, is discussed. The results of robust methods that consist in downweighting the influence of the multivariate outliers are compared with the outcomes of classical procedures. The advantages of modern robust algorithms are proved in the present study. It is planned to include the methods in the system for the computerized consulting unit for respiratory diseases that is being set up in Wroclaw. PMID- 2214920 TI - Graphical output of health testing data. AB - A new indicator to evaluate the health status of an examinee by computerizing selected health screening data has been devised and designated as a disease score. By employing such an index, it is possible to display to some extent the functional status of organs in simple, easily understood, computer-generated cartoons. Thus a computer program has been developed for a desk-top personal computer to calculate the disease score index from screening data and to generate an output in an easily understandable graphic and pictorial format. The disease score index with a graphic display (i.e., a disease map), a score graph and short comments are incorporated in the report form. This type of output should be especially useful in communicating with subjects who are screened and in helping them to understand selected aspects of their own state of health better. The index could also be helpful in screening and selecting subjects who require further detailed clinical examinations but this assumption needs full clinical evaluation to prove its efficacy. PMID- 2214921 TI - A menu-driven knowledge base browsing tool. AB - Conventional computer-assisted medical decision-making systems have had limited impact on routine clinical practice. This has stimulated an alternative approach to the utilization of medical knowledge bases. Centering on the storage and retrieval of medical information, it aims to provide clinicians with computerized medical reference systems. In this paper we describe the development of a prototype menu-driven browsing tool, which allows clinicians to browse through the contents of a knowledge base in a number of ways. Operations include interrogation via disease classes, names or attributes; hierarchical display of all or part of a disease profile; printing of a disease profile; construction of differential diagnosis lists and comparison of two diseases. We discuss how the use of a menu-driven interface can help to overcome some of the problems encountered with previous designs of medical reference systems. PMID- 2214922 TI - [Angioimmunoblastic lymphadenopathy with dysproteinemia. The first reported case at the "Santo Tomas" Hospital]. AB - Description of the first case of angio-immunoblastic lymphadenopathy with dysproteinemia diagnosed in a male patient 64 years old and which preceded the development of a lymphoma. The importance of this study is the association that may exist between certain drugs and the development of angioimmunoblastic lymphadenopathy, which occurred in our patient with the use of diphenylhydantoin. This disease can present itself up to 22 years after exposure to the agent. PMID- 2214923 TI - [Effect of minoxidil on DNA synthesis in cultured fibroblasts from healthy skin or keloids]. AB - A potential therapeutic role of minoxidil in fibrotic or sclerotic conditions, such as keloids, has been suggested on the basis of its reported ability to inhibit the proliferation of human dermal fibroblasts. We have studied the effect of minoxidil on 3H-deoxythymidine uptake in cultures of human dermal fibroblasts derived from lesional and non-lesional skin from patients with keloids. The effect of the addition of fetal bovine serum, plasma and growth factors (insulin, EGF, PDGF, FGF and beta-TGF) to the medium has also been studied. Minoxidil, at concentrations ranging from 500 to 1,000 microM., caused an increase in DNA synthesis, which was proportional to the initial degree of fibroblast activation. Concentrations higher than 1,000 microM. caused a cytotoxic effect. Some reservations arise on the potential therapeutic use of minoxidil in conditions characterized by increased fibroblast proliferation, given the narrow margin between activation of DNA synthesis and cytotoxicity we have found in our experimental model. PMID- 2214924 TI - [Evaluation of immune response in experimental sporotrichosis using T and B lymphocyte count]. AB - The effector cells of the immune response are involved in the clinical course of bacterial, viral and mycotic infections. Previous publications have reported that some mycotic infections, including sporotrichosis, can produce a negative modulation of the immune response unfavorable for the host. In this work T and B lymphocytes capable to form direct and indirect rosettes respectively with sheep erythrocytes in gerbils with experimental sporotrichosis, were measured. It was found a significant rise in the number to T and B lymphocytes which means normal immunological reactivity. These results are not in accordance with the idea that sporotrichosis can depress the immune response of the host. PMID- 2214925 TI - [Multiple familial trichodiscoma]. AB - Trichodiscomas are hamartomas of the pilar apparatus, and have been described alone or associated to other benign proliferations of the pilar complex. Two familial cases of trichodiscomas not associated to pilar alterations or systemic manifestations are described. PMID- 2214926 TI - [Tubular apocrine adenoma. Description of 4 cases]. AB - We present four new cases of tubular apocrine adenoma. Clinical histopathological and ultrastructural findings are discussed. The presence of carcinoembryonic antigen (CEA) has been studied in three cases of tubular apocrine adenoma. This antigen was found predominantly in the lumen of the ducts and in the apical portion of the luminal cells. This pattern is similar to the distribution described in normal sweat glands and in other adnexal tumors. PMID- 2214927 TI - [Recurrent intertrigo as initial manifestation of histiocytosis X]. AB - Letterer-Siwe disease is the acute and usually fatal form of histiocytosis X. We describe here a patient with this process, which serves as a reminder of the presenting features of histiocytosis X. PMID- 2214928 TI - [Amelanotic melanoma. Study of 18 cases]. AB - The authors analyze a retrospective study of 18 cases of amelanotic melanoma, coming from 7 Departments of Dermatopathology, and 3 from private clinics in Brazil, during the period from 1980 through 1987. Nine of the 18 patients were men, and seven were women; 14 of the 18 were caucasian and 2 were blacks. Their average combined age was 56 years, varying from 24 years to 86 years. The average size of the lesions was 2.7 cm. and the location was: extremities = 7, thoracic wall = 5, upper limb = 2, and lower limb = 2. Only 2 cases included in this analyses, didn't have any other additional information about color, age, sex and location. The authors found that amelanotic melanoma is rare, in accordance with the literature. They point out, that the rarity or the lack of the melanic pigment within the tumors cells, makes the clinical diagnosis much more complex. PMID- 2214929 TI - [Perforating annular granuloma in an atypical location]. AB - We report a case of perforating granuloma annulare characterized by a scare number of lesions, that were located around breast areola. The patient was a young female without personal or family remarkable history. PMID- 2214930 TI - [Treatment of condylomata acuminata using liquid nitrogen]. AB - We treated 105 patients with anogenital warts with cotton swabs soaked in liquid nitrogen. 90.1% of the patients were cured, but recurrences were observed in 19.5%. With this method we obtained better clinical results than those obtained with the cryoprobes system. Good results were obtained when the lesions were accessible for treatment, but neither the time of evolution nor the size influenced the cure. PMID- 2214931 TI - [Treatment of skin ulcer using oil of mosqueta rose]. AB - Oil rose of mosqueta (Rosa aff. Rubiginosa L.) is a concentrated solution in linoleic (41%) and linolenic acid (39%), that offers benefit therapeutic effects in the wound healing. Ten patients affected of leg ulcers and post-surgical wounds were treated by 26% oil concentrated rose of mosqueta with very notable improvement on its healing compared with the control group. Due to the lack of side effects, we believe rose of mosqueta oil is very usefull to these conditions. Mechanism of actions and others indications are discussed. PMID- 2214932 TI - [Apocrine nevus]. AB - We present the case of a 32-year-old woman with a congenital lesion on her left cheek that histopathologically was composed of numerous mature apocrine glands. The diagnosis of pure apocrine nevus, a rare lesion of that our case probably represents the sixth described in the literature, was made. PMID- 2214933 TI - [Skin and ungual pigmentation caused by ftorafur]. AB - We report the case of a sixty-seven-years-old male diagnosed of a gastric adenocarcinoma that presented brown pigmentation in the dorsal of his both hands and fingernails while being on treatment with ftorafur, an analogous of 5 fluorouracil. To our knowledge this side effect has not been previously reported for ftorafur. PMID- 2214934 TI - [Pedal papules in newborn infants]. AB - Four cases of newborn children who presented pedal papules since birth, are reported. They showed the following features, different from the ones seen in adults: a solitary lesion, bigger size, localization on medial plantar region aspect of the heel, presence at birth, absence of an obvious piezogenic factor, physiopathogenic model that explains the development of lesions in adults, which are compared to those appearing in the newborn, are proposed. PMID- 2214935 TI - [Pseudoatrophic pityriasis versicolor]. AB - The pseudoatrophic pityriasis versicolor is an atypical form of this disease with cutaneous atrophy provoked by the prolonged application of topical corticosteroids. The term "pseudoatrophic" is indicative of its reversible character. PMID- 2214936 TI - [Cystic lymphangioma]. AB - A case of clinical and dermopathological characteristic cystic lymphangioma is reported. The atypical localization of the tumor and its delayed apparition were pointed out. A relation with any precipitating factor could not be established. Treatment was surgical remove. PMID- 2214937 TI - [Vascular nevus. A study of its frequency, types and course]. AB - It is presented a prospective study of vascular nevus during a year, with the finality to know its frequency, types and evolution. In twelve months of study, we founded in 1,485 borns that 14.14% presented those lesiones salmon stain 86%, oport wine 1.35%, capilar hemangioma or in strawberry the 10.81%, cavernous hemangioma the 0.45% and mixed hemangioma the 1.35%. Where more frequent in females that in males as well as from the urban zone in almost more than the half of the cases. Dimensions were between 0 to 5 cm. range, 98% in salmon stain, 95% in strawberry hemangioma, 66.3% mixed hemangioma, 66.6% in oport wine stain distributed in the head in more proportion. There was salmon stain in the nape in 61.7%, 15% in the forehead and in the superior eyelids 14.3%. The familiar antecedents of vascular nevus in brothers was of 4.76%, 5.71% in uncle, 2.98% in parents and 1.43% in grandparents. The evolution was not concluded because of desertion in almost the totality of patients, finalizing with only the 6.66%. Our findings are different from those published in the literature. The total frequency is more in our experience in salmon, oport wine stains and hemangiomas. PMID- 2214938 TI - [Cutaneo-visceral leishmaniasis: a new opportunistic infection in patients infected by HIV]. AB - A HIV infected patient was admitted to hospital with fever diarrhoea and a cutaneous nodule on his left groin. Histopathological exam was diagnostic of cutaneous leishmaniasis. Subsequent exams disclosed Visceral Leishmaniasis. Three cycles of treatment (antimonials, pentamidine and metronidazole) were required for the clearance of lesions. The relation between immunosuppression and leishmania infection is commented and its role as an opportunistic pathogen is suggested. In these patients the infection takes a more aggressive course and has a worse response to the classic treatment with antimonials. These facts have made necessary the introduction of other alternative drugs. PMID- 2214939 TI - [Wells syndrome (3 cases)]. AB - This report describes three cases of eosinophilic cellulitis (Wells' syndrome) observed during six years. In the author's opinion this condition is not frequent, but neither exceptional. A revision of clinico-pathological, etiopathogenic and therapeutics aspects is carried out. PMID- 2214940 TI - [Eosinophilic cellulitis (Wells syndrome)]. AB - There is a 37 years old patient with a erythemato-nodular pathology on her lower limbs, which has relapsed during three years. The characteristics of the eosinophilic cellulitis are observed in the microscopic study. The clinical and laboratory attributes of this entity are discussed, according to the world medical literature. PMID- 2214941 TI - [Hypersensitivity in patients with Hebra's prurigo caused by flea bite]. AB - The authors present a study of hypersensitivity of patients with Hebra's prurigo (HP) to feleabites. Thirty six patients were studied. With the results obtained the following conclusions are held: 1. Among the probable responsible factors found in the history of patients with HP, the flea bite is the principal factor. 2. Almost all the patients with HP who were studied show hypersensitivity to flea bites. 3. With the flea bites on the patients with HP, one can observe the clinical and histopathology similarity of both the experimental and elementary lesions of the disease. 4. It was possible to show humoral antibodies in the serum of the patients with HP immunodiffusion technique to the 1:40 flea extract. PMID- 2214942 TI - [Idiopathic skin calcinosis with transepithelial elimination]. AB - A case of universal cutaneous calcinosis developed without apparent cause is reported. It had an evolution towards epidermic perforation and was treated with aluminium hydroxide. A discussion was made on the rarity of the idiopathic calcinosis as well as on the interesting phenomenon of transepidermal elimination. PMID- 2214943 TI - [Sea-blue histiocytes in a patient with mycosis fungoides]. AB - The syndrome of the sea-blue histiocyte is a multisystemic infiltration by a special kind of macrophages which contain a ceroid material within its cytoplasm. We report herein a patient with mycosis fungoides, hyperlipidaemia type IIB and sea-blue histiocytes on bone marrow. Moreover, the cutaneous histopathology showed focus of eosinophilic spongiosis, that have not been previously described in mycosis fungoides, as far as we know. PMID- 2214944 TI - [Subungual keratoacanthoma]. AB - We present a case of subungueal keratoacanthoma. The tumor recurred three months after extirpation and didn't resolve spontaneously. The patient need a new surgery a year later. We revised the literature and comment the clinical and histological features that define this distinct entity and differentiate it from common keratoacanthoma and subungueal squamous cell carcinoma. PMID- 2214945 TI - [Systemic calciphylaxis and acquired perforating disease in a uremic patient]. AB - We show the case of a patient suffering from a chronic renal failure in hemodialysis. He had a ischemic necrosis that was quickly progressive in his fingers and toes. It was necessary to amputate them. Diffuse vascular calcifications were recorded so radiologically than pathologically. PTH and phosphocalcic product were raised. Parathyroidectomy was practised with a quick initial improvement but immediately new distal ischemic lesions and keratotic papules with histologic perforation, that became necrosed, appeared in his buttocks and inferior extremities. The coexistence of acquired perforating disease and calciphylaxis in uremic patients has not been reported until now. PMID- 2214946 TI - [Dowling-Degos disease]. AB - We report two cases of Dowling-Degos' disease, one affecting the vulvovaginal semimucose, and one associated to a terminal malignant neoplasia. We remark the importance of this knowledge in order to distinguish it from malignant acanthosis nigricans or other patterns of melanosis or lentiginosis when located within mucose or semimucose, specially at the genitals. All cases associated to malignant neoplasia described are emphasized. However Dowling-Degos' disease is considered to be a nonparaneoplasic genodermatoses, this association should be taken into account. PMID- 2214947 TI - Physicians at the Ottoman court. PMID- 2214948 TI - The anodyne necklace: a quack remedy and its promotion. PMID- 2214950 TI - Medical complications associated with security and control of prisoners of war in the ancient Near East. PMID- 2214949 TI - Wagner-Jauregg and fever therapy. PMID- 2214951 TI - Robert Pulvertaft's use of crude penicillin in Cairo. PMID- 2214953 TI - [The highest risk of sport injuries at school affects inactive children]. PMID- 2214952 TI - The Eugenics Society archives in the Contemporary Medical Archives Centre. PMID- 2214954 TI - [Long-term lithium treatment has side effects]. PMID- 2214955 TI - [Improved medical care, even if only for half of the population]. PMID- 2214956 TI - [Mechanical ventilation at home: Multidisciplinary care is crucial for optimal treatment]. PMID- 2214957 TI - [Remember the physiopathology when treating patients with chronic venous insufficiency]. PMID- 2214958 TI - [Relationship between volume and results--does it exist in the Swedish vascular surgery?]. PMID- 2214959 TI - [Separation of Siamese twins. Neither child was given preference]. PMID- 2214961 TI - [A case of lethal theophylline poisoning. Slow-release preparation gave treacherous and late symptoms]. PMID- 2214960 TI - [Sven-Ivar Seldinger. Severe attack of common sense resulted in a revolutionary catheterization technique]. PMID- 2214963 TI - [SBU report: shockwave lithotripsy of renal stones is recommended. In the case of gallstones more clinical trials are necessary]. PMID- 2214962 TI - [Dietary therapy in practice. Advice on food--more than just knowledge of human nutrition]. PMID- 2214964 TI - [Falsified prescriptions--a widespread way of acquiring drugs?]. PMID- 2214965 TI - [Comparison of 2 surveys: medical competence at the casualty departments in our country]. PMID- 2214966 TI - [Ready-for-discharge patients--an unnecessary scourge?]. PMID- 2214967 TI - [Heart-lung transplantation--indications, results, need]. PMID- 2214968 TI - [Should normal short stature be treated with drugs?]. PMID- 2214969 TI - [Bone lengthening in short stature individuals--not without problems]. PMID- 2214970 TI - [Gastric tube insertion without discomfort of the patient]. PMID- 2214971 TI - [Small changes in cancer mortality. Time for a bigger prevention drive?]. PMID- 2214972 TI - [Preoperative calculation of eyeglass lens power after cataract surgery]. PMID- 2214974 TI - [New medical therapy of neuroendocrine gastrointestinal tumors]. PMID- 2214973 TI - [Leg lengthening--historical review and current techniques]. AB - The techniques earlier used for leg lengthening were notorious for their complications, and as late as the 1960s some authorities would not consider lengthening unless amputation was the alternative. The method introduced by Wagner in the 60s had the advantage of a stable external fixation, permitting the patients to be mobilized. The drawback was that at least three operations were needed: external fixation and osteotomy, bone grafting and internal fixation, and, finally, removal of the plate. With the Ilizarov technique, no bone grafting is needed and bone lengthening up to at least 15 cm is possible. The main problems in leg lengthening are related to joints and soft tissue. Every surgeon performing leg lengthenings should be familiar with the possible problems and complications. He must establish very good relations with the patient and be ready to spend a considerable amount of time with the patient during the process. PMID- 2214975 TI - [Dyslexia, a serious disability]. PMID- 2214976 TI - [The late effects of nuclear weapons will destroy the human immune system]. PMID- 2214977 TI - [Health care in Australia. Easy, convenient and inexpensive to consult a physician]. PMID- 2214978 TI - [Anamnesis and elimination are corner-stones in the diagnosis of hypersensitivity reactions]. PMID- 2214979 TI - [Cholesterol screening in a healthy father of 4 children--an ethical dilemma for the district physician]. PMID- 2214980 TI - [Medical examination for driver's licence. The government disagrees with medical experts regarding the driver's licence of insulin-dependent diabetics]. PMID- 2214981 TI - [Basic medical education--who cares?]. PMID- 2214982 TI - [400,000 donation cards for transplantation available in Sweden]. PMID- 2214983 TI - [Laser--a well-established medical routine sometimes with doubtful applications]. PMID- 2214984 TI - [Hepatitis B is less and less common in spite of the increased number of new HBsAg carriers]. PMID- 2214986 TI - [While the number of carriers with hepatitis B is increasing the number of acute cases decline]. PMID- 2214985 TI - [An electrochemical instrument ineffective for capillary blood glucose determination]. PMID- 2214987 TI - [Measurement of smoking habits and other life style factors should be adjusted]. PMID- 2214988 TI - [HBsAg positive children in child day care centers--experience from Gothenburg]. PMID- 2214989 TI - [Self administration of antibiotics in traveller's diarrhea. Advantages are not in balance with the risks]. PMID- 2214990 TI - [Cancer treatment can be "tailor-made" with laser surgery and photochemistry]. PMID- 2214992 TI - [A conservative method of laser surgery for urinary tract tumors]. PMID- 2214991 TI - [A successful laser method in vascular changes and post-cataract surgery]. PMID- 2214993 TI - [Calcification was dissolved as sugar in hot water]. PMID- 2214994 TI - [From knife to light beam for more conservative conization]. PMID- 2214995 TI - [Swift development of neurology]. PMID- 2214996 TI - [Almost 3 million fatal injuries are caused by accidents yearly]. PMID- 2214998 TI - [Cefuroxime has a good effect in severe infections in children]. PMID- 2214999 TI - [Is levamisole combined with fluorouracil efficient in colorectal cancer?]. PMID- 2214997 TI - [How strong is the defense for dynamic psychology?]. PMID- 2215000 TI - [Fear of boycott keeps companies from registering early abortion drugs]. PMID- 2215001 TI - [Maidenhood--mostly a myth]. PMID- 2215002 TI - [Early diagnosis of pons angle tumors can rescue the hearing]. PMID- 2215004 TI - [Erythromycin caused liver injury and gallbladder inflammation]. PMID- 2215003 TI - [Maternal health care must improve its tracing of hepatitis B virus carriers]. PMID- 2215005 TI - [Glycosylated hemoglobin, a useful test in screening for diabetes mellitus]. PMID- 2215006 TI - [Intrauterine infection an important cause of pregnancy complications]. PMID- 2215008 TI - [May we live until retirement?]. PMID- 2215007 TI - [Life situation is crucial for well-being of women after hysterectomy]. PMID- 2215009 TI - [An inquiry on sexual habits among students causes concern for wider transmission of HIV]. PMID- 2215010 TI - [Chemical structure of the Candida receptor is surveyed. A potential for treatment and vaccination]. PMID- 2215011 TI - [The autopsy law and the probable cause of death]. PMID- 2215012 TI - [After hysterectomy. Few postoperative complications. The sexual function is unchanged or improved]. PMID- 2215013 TI - [Scleroma is a granulomatous infectious disease starting with diffuse respiratory tract symptoms]. PMID- 2215014 TI - [Artificial insemination in involuntary sterility. A consensus statement against expert-based facts--IVF is banned, microsurgery praised]. PMID- 2215016 TI - [A government survey and program of the medical society: tobacco policy in the 1990's]. PMID- 2215015 TI - [The man behind the syndrome. Hans Asperger and the unknown autism. The Asperger man--a reserved outsider exposed to enormous psychological strain]. PMID- 2215017 TI - [Health situation in Eastern Europe is severe--is the gap between East and West going to diminish?]. PMID- 2215018 TI - [Health care societies against the death penalty]. PMID- 2215019 TI - [Trauma with septicemia. Time to reevaluate treatment with antibiotics?]. PMID- 2215020 TI - [Chlamydia infection--a sexually transmitted disease in the shadow of AIDS]. PMID- 2215021 TI - [New guidelines for the treatment of hypertension--what has really happened since the last time?]. PMID- 2215022 TI - [European cooperation for health education in schools]. PMID- 2215023 TI - [A revival of inhalation anesthesia. Reduced risk of liver toxicity]. PMID- 2215025 TI - [Macular degeneration--a treatable disease?]. AB - Age-related macular degeneration (AMD) is the most common cause of blindness over the age of 50. The patho-physiological changes and clinical findings in AMD are outlined. Recent findings indicate that some cases of AMD-related choroidal neovascularization can be successfully treated with argonlaser. These results are discussed from a Swedish perspective, and the need of a meticulous work-up is emphasized. PMID- 2215024 TI - [New discoveries in joint disease etiology. Biochemical markers are promising]. PMID- 2215026 TI - [Transoral microsurgery as effective treatment of craniocervical diseases]. PMID- 2215027 TI - [Trauma surgery in the USA (I): Many severe accidents--high working pace]. PMID- 2215028 TI - [Trauma surgery in the USA (II): Restricted use of antibiotics in septic reaction after multiple trauma]. PMID- 2215030 TI - [Medical ethics and ethical rhetoric--analysis of arguing makes the debate on ethics better]. PMID- 2215029 TI - [Recommendations from a meeting of experts: treatment of urinary tract infections]. PMID- 2215031 TI - Conservation surgery for glomus jugulare tumors: the value of early diagnosis. AB - The results of lateral cranial base surgery for glomus jugulare tumors are gratifying when normal anatomy and function can be preserved. The goal of conservation surgery is to preserve normal ear anatomy and cranial nerve function. In general, conservation surgery is tumor-size dependent. Thus, excellent states of functional recovery depend upon accurate early diagnosis. This paper reviews the technical aspects of transtemporal conservation skull base tumor surgery while also reviewing our experience with nearly 100 glomus jugulare patients. Adjuvants to early diagnosis will be highlighted from a review of presenting symptoms, clinical signs, and related diagnosis. Our objective is to provoke a high index of suspicion in physicians charged with the responsibility of diagnosing these tumors. Diagnostic guidelines are proposed. PMID- 2215032 TI - The location of the maxillary os and its importance to the endoscopic sinus surgeon. AB - As functional endoscopic sinus surgery continues to gain popularity and support, the necessity for a clear and accurate understanding of the anatomy of the ostiomeatal complex becomes essential. To clarify this anatomy, serial cadaver dissections were performed and the anatomy of the ostiomeatal complex was detailed in three dimensions, with an emphasis on precise localization of the internal os of the maxillary sinus as it relates to the orbit, natural antronasal canal, and ethmoid infundibulum. Measurements of the position of the internal os relative to the position of the anterior and posterior walls of the maxillary sinus and the position of the orbit were taken. The dimensions and configuration of the antronasal canal and its relationship to the infundibulum were also detailed. These measurements and relationships must be understood for an endoscopic sinus surgeon to locate the natural ostia without injuring the orbit. PMID- 2215033 TI - Surgery for sinusitis and aspirin triad. AB - An 11-year retrospective study was conducted to evaluate the surgical treatment of sinusitis in aspirin-triad patients. Twenty-five patients were selected for surgery when their sinus disease and asthma progressed despite intense medical treatment. Sixteen patients had radiographic evidence of severe ethmoid disease, and their initial surgical procedures were limited (i.e., bilateral intranasal ethmoidectomies). Of these 16 patients, 6 required subsequent surgery for recurrent sinusitis. Nine of the 25 patients had radiographic evidence of severe antral, as well as ethmoid, disease. Their initial surgical procedures were radical, i.e., bilateral Caldwell-Luc operations with intranasal and transantral sphenoethmoidectomies. None of these 9 patients required further surgical treatment for control. This review indicates that if antral and sphenoid disease are detected in association with ethmoid involvement, a radical surgical approach is the operation of choice. PMID- 2215034 TI - Local control of auricular, periauricular, and external canal cutaneous malignancies with Mohs surgery. AB - Three hundred ninety-seven patients with 407 cutaneous malignancies of the auricle, periauricular region, and cartilaginous external ear canal were reviewed. Tumors were most commonly located in the preauricular and postauricular regions, followed by the helix, concha, antihelix, and ear canal. All lesions were excised with Mohs microscopic control of margins. For lesions requiring lateral temporal bone resection, an adaptation of fresh-tissue microscopic control was used to analyze deep and anterior margins suspected of harboring residual tumor. Two-year minimum follow-up of 229 patients with periauricular and auricular tumors (N = 231 tumors) and 14 patients with cartilaginous ear canal tumors (N = 14 tumors) revealed recurrence rates of 6.9% and 14.3%, respectively. Recurrences were most common in cases of large tumors (greater than 2.5 cm), basal cell carcinomas with morphea elements, and multiply recurrent lesions. We conclude that Mohs surgery is comparatively effective, though not uniformly curative, and can be adapted to supplement excision of large tumors in these regions. PMID- 2215035 TI - Olfactory neuroblastoma: clinicopathologic and immunohistochemical characterization of four representative cases. AB - Olfactory neuroblastomas are rare tumors whose clinical prognosis is not predictable by assessment of initial stage or grade. The pathologic diagnosis is often difficult because of the wide range of the patient's age and histologies. In this report, we document that the diagnosis of olfactory neuroblastoma can be clarified by immunohistochemical demonstration of a unique antigenic profile that can be obtained in routinely processed biopsies. We describe four cases of olfactory neuroblastoma diagnosed and treated from 1979 to 1989, each confirmed by immunohistology. One of our patients was misdiagnosed twice at an outside institution, first as having nasopharyngeal carcinoma and then as having small cell, undifferentiated "oat cell" carcinoma. Despite accurate tumor diagnosis and appropriate therapy, we found that there was no apparent correlation of clinical outcome with Kadish clinical stage or histologic grade of tumor. PMID- 2215036 TI - Lidocaine in the middle ear. AB - Anesthesia of the ear canal is produced by injection of lidocaine hydrochloride into the skin of the lateral external ear canal. Ear canal, tympanic membrane, and middle ear surgeries are performed with this injection. The fluid found in the middle ear during tympanotomy was collected and analyzed. The percentage of lidocaine in the fluid was calculated by an enzyme immunoassay technique. Fifteen surgical cases were undertaken in which perilymphatic fluid in the middle ear would not be suspected, such as tympanotomy for otosclerosis. Lidocaine was found in all middle ears in which there was sufficient fluid to collect. The authors question the validity of using the presence of clear fluid in the middle ear, even with reaccumulation, as the sole criterion for identifying perilymph and cerebrospinal fluid. PMID- 2215037 TI - Managing segmental facial nerve injuries by surgical repair. AB - This report describes our experiences and evolving philosophy with regard to managing segmental facial nerve injuries. We present the results of 13 facial nerve repairs of traumatic injury to a segment of the facial nerve. All peripheral facial nerve branches contribute essential elements to normal mimetic facial movement; therefore, we recommend early, appropriate repair of the nerve segment. This recommendation is based on principles established for managing disruptions of the main trunk of the facial nerve. It offers the patient the chance for complete recovery of facial function. PMID- 2215038 TI - Effects of uvulopalatopharyngoplasty on sleep architecture and patterns of obstructed breathing. AB - In this retrospective study, 72 obstructive sleep apnea patients with polysomnograms taken before and after uvulopalatopharyngoplasty were evaluated. Postoperatively, there was a significant improvement of sleep architecture and respiratory indices. In addition, a second group of 17 patients also had position recordings with their polysomnograms. Time spent in supine and lateral sleep positions changed postoperatively. There was significant decrease of the apnea plus hypopnea index in the lateral position. This study indicates that there is significant improvement of sleep architecture and respiratory indices in the majority of patients after uvulopalatopharyngoplasty, particularly in the lateral sleep position. PMID- 2215039 TI - Imaging of pharyngeal and laryngeal carcinomas with indium-111-labeled monoclonal anti-CEA antibodies. AB - Localization of primary tumors, metastases, or recurrences in 13 consecutive patients with histological verification of squamous cell or adenocarcinoma was made with radioimmunodetection using monoclonal radiolabeled anti-CEA antibody. All surgical specimens stained immunohistochemically, except one, were positive for CEA. Of the known 19 tumor sites 17 were visualized in antibody scans. There were two positive findings that did not prove to be positive during 12 month follow-up. The scintigram findings did not correlate with CEA serum concentrations that, with one exception, were normal in all patients. PMID- 2215040 TI - The role of the facial nerve latency test in the prognosis of Bell's palsy. AB - Eighty patients with idiopathic facial nerve palsy were evaluated by the facial nerve latency test. Depending on the latency time, the patients were classified into the following four groups: group A patients had normal latency times (3.25 msec); group B patients had slightly extended latency times (4 to 7 msec) and a mean of 5.6 msec; group C patients had extended latency times (10 to 14 msec) and a mean of 10.2 msec; and group D patients displayed complete disappearance of evoked compound muscle action potential (no responses). Under the same therapeutic regimen, it was determined that, when the latency time was normal or close to normal, the functional recovery of the nerve was complete or almost complete, and the recovery time was short. When the latency time was extended or there was no response, the functional recovery of the nerve was either incomplete or absent. PMID- 2215041 TI - Surgical therapy of the eyelids in patients with facial paralysis. AB - Patients with facial paralysis have a degree of lagophthalmos and paralytic ectropion. We present our experience in the surgical management of 25 consecutive patients treated for these problems. Paralytic lagophthalmos was corrected using gold weights inserted into the upper eyelid. The advantages and disadvantages of this surgical technique are reviewed. Medial canthoplasty and lateral canthoplasty were performed to rectify paralytic ectropion. Ancillary procedures included browpexy, upper-lid blepharoplasty, and temporalis sling. The results were excellent in 23 of 25 patients and good in the remaining two. After a minimum of 6 months' follow-up, there were no complications. The authors believe that the above procedures will yield consistently excellent cosmetic and functional results in patients with paralysis of the eyelids. PMID- 2215042 TI - Stapedotomy technique and results: ten years' experience and comparative study with stapedectomy. AB - Fifty of the 810 patients who underwent stapedotomy for otosclerosis from 1969 through 1988 were randomly chosen for follow-up of at least 5 years. Most of the patients (65%) had follow-up of 10 years after stapedotomy, but another 50 patients who underwent stapedectomy had follow-ups of longer than 10 years. In 50 patients, stapedectomy under local anesthesia was performed by removal of the footplate of the stapes, using an endaural incision, and covering the oval window with Gelfoam. In the other 50 patients, stapedotomy was performed under general anesthesia, using an endopreauricular incision, making a small hole in the footplate, and covering the hole only with blood from the surgical area. Although both groups showed improvement in hearing after the operation, the air-bone gap in the stapedotomy group was significantly better than that in the stapedectomy group. The use of the endopreauricular incision under general anesthesia was preferable to endaural incision under local anesthesia because the operative field was wider, more convenient for the surgeon, and conducive to patient safety. There were no significant complications in either group. PMID- 2215044 TI - Clinical classification and staging for primary malignancies of the maxillary antrum. AB - A study of 51 patients with primary malignant maxillary sinus neoplasms was conducted. None of the patients had neck nodes and/or metastases, and each had 5 year follow-up. The tumors were staged according to the 1983 and 1988 American Joint Committee on Cancer staging systems for maxillary sinus cancers. There were 13 early stage (T1, T2) and 38 advanced (T3, T4) tumors in both systems. Cox regression analyses of survival curves showed increasingly worse prognoses for advanced tumors in both T-staging systems. Further analyses showed a significant difference in survival between T3 and T4 in the 1988, but not in the 1983 system. There were no significant differences in survival according to treatment modality or histological type of malignancy. We conclude that the 1988 system prognosticates successfully for T-stage (1 to 4) and demonstrates significant improvement in detecting T3 versus T4 differences compared to the 1983 system. The 1988 system applies equally for epidermoid cancer and other malignancies of the antrum. PMID- 2215043 TI - Endoscopic laser surgery for early glottic carcinoma: a clinical and experimental study. AB - The purpose of this study is to define the indications for using the CO2 laser for the treatment of early glottic cancer. For this purpose, 52 consecutive laser resections of Tis to T2 vocal cord carcinomas were studied prospectively. In addition, laser resection was performed in eight human cadaver larynges, which were then examined histologically using whole organ sections. Both tumor size and tumor location had important influences on tumor resectability by laser. All of the Tis, 78% of T1, and one of four T2 carcinomas were successfully treated by laser surgery alone. Of the 10 carcinomas involving the anterior commissure, only four could completely be resected with the laser; of these four, two recurred in the anterior commissure. This finding is corroborated by the histologic study, which clearly shows that anterior commissure resection poses problems. The only laser resection complication of early glottic cancer was persistent hoarseness in one third of the patients. It is concluded that CO2 laser resection is a safe and effective alternative treatment for patients with Tis and T1 glottic carcinoma, provided the anterior commissure is free of tumor. PMID- 2215045 TI - Gentamicin iontophoresis in the treatment of bacterial otitis externa in the guinea pig model. AB - Pseudomonas otitis externa is one of the most common infections treated by otolaryngologists. Infections induced in 30 guinea pigs appeared similar to that seen in humans. The ears were then placed into four treatment groups: group A, which received a single cleaning; group B, which received a single cleaning followed by gentamicin drops 4 times daily; group C, which received a single cleaning followed by a single gentamicin iontophoresis treatment; and group D, the control group, which received no treatment. Infections were analyzed by grading edema, purulence, and erythema. An average of 10.2 days was required for control group to return to normal appearance. Groups A, B, and C had mean resolution times of 5.9, 4.7, and 4.3 days, respectively. Gentamicin iontophoresis appears to be promising, with results as good as drop therapy in otitis externa in the guinea pig model. PMID- 2215046 TI - Verbal communication for the ventilator-dependent patient: voice intensity with the Portex "Talk" tracheostomy tube. AB - A patient's ability to communicate is critical to overall medical care, psychological functioning, and social interactions. Voice intensity levels produced by 20 patients with Portex "Talk" cuffed speaking tracheostomy tubes were investigated at three different airflow rates. Results indicated that audible and intelligible speech was produced with significantly greater intensity (P less than .001) over ambient room noise at 5 l/minute, 10 l/minute, and 15 l/minute of airflow. Also, significantly greater voice intensity (P less than .001) was noted as airflow increased from 5 l/minute to 10 l/minute and from 10 l/minute to 15 l/minute. The criteria, rationale, and importance of using a speaking tracheostomy tube with cognitively intact ventilator-dependent patients are discussed. The specific advantages and disadvantages of the Portex "Talk" tracheostomy tube are delineated. A case study is included. PMID- 2215047 TI - Data management without data managers: an effective standardized system of otolaryngologic operative reporting. PMID- 2215048 TI - A new method of needle-electrode placement in the posterior cricoarytenoid muscle for electromyography. AB - In 1979 the authors developed a new method of needle-electrode placement in the posterior cricoarytenoid muscle (PCA) for electromyography. The PCA muscle is easily reached by inserting a needle electrode through the cricothyroid membrane at the midline and penetrating the lamina of the cricoid cartilage in the subglottic cavity. Access to the PCA muscle for electrode insertion was best afforded by a percartilaginous approach. This report details the new technique used at our laboratory. To our knowledge, this is the first report of needle electrode placement in the PCA muscle by a percartilaginous approach. This new electrode insertion technique has been applied to more than 100 dogs for research purposes and to 1200 patients with laryngeal motor disorders for clinical diagnosis. This is a simple technique requiring the usual skills. Reliable electromyographic recordings have been obtained by this new method. No untoward effects, such as hematoma or infection from repeated placements were observed in approximately 3200 examinations performed to date. It is reasonable to assume that the percartilaginous route for electrode insertion in the PCA muscle is feasible in man. Techniques of electrode placement in the intrinsic laryngeal muscles are reviewed and compared. PMID- 2215049 TI - An improved stent method for choanal atresia repair. AB - Short intranasal stents secured sublabially have a number of advantages. They provide secure fixation without an external ligature across the columella. The short length of the stents allows them to sit only in the operative area where the atretic plate had been removed. This lessens the chance of intranasal syechiae formation and eliminates the possibility of erosion in the anterior septal and nasal alar region from pressure exerted by a stent. Since the stents do not protrude from the nose, they cannot be grasped by infants or young children and are not visible externally. School-aged children who have undergone repair of a unilateral choanal atresia can attend school without having to suffer the embarrassment of being teased about a tube protruding from the nose. When compared with other stenting methods, the posterior stent is more secure and less likely to become dislodged. PMID- 2215050 TI - Hearing levels of railroad trainmen. PMID- 2215051 TI - Non-ossicle homograft bone prostheses in the middle ear. AB - This thesis proposes the use of human cadaver non-ossicle temporal homograft bone as middle ear reconstructive material. Bone obtained from the otic capsule histologically resembles that of the ossicles more so than any other bone in the body. The otic capsule, due to its proximity to the middle ear, can be harvested with the middle ear structures when bone cores are obtained, making it easily accessible. These prostheses are cost effective because multiple prostheses can be sculptured from one temporal bone core. This paper further proposes the use and introduction of non-ossicle homografts in primary stapedectomy, as well as in selected cases to bypass the incus and the superstructure of the stapes. Audiological data is provided. Some of the grafts have been in the middle ear for up to 5 years. There have been no extrusions and no complications. The method of harvesting, preservation, and sterilization is presented, as well as a pictorial illustration of the finished product and its relation to the natural ossicles. One histological specimen is presented. On the basis of the audiologic results, as well as the fact that no ossicles have extruded and none have been resorbed, it is proposed that non-ossicle temporal bone homografts have a place in transplantation surgery. PMID- 2215052 TI - Dermatology--global planning in relation to leprosy management. PMID- 2215053 TI - Armauer Hansen Research Institute 1970-1990. PMID- 2215054 TI - The evolution of antibody response in armadillos inoculated with Mycobacterium leprae. AB - Plasma from 30 armadillos (Dasypus novemcinctus) was collected prior to inoculation and at approximately 3-month intervals for a period of 1-3 years. These animals were inoculated intravenously with 6.1 x 10(8) +/- 2 x 10(8) (x +/- SD) armadillo-derived Mycobacterium leprae. These samples were analysed for antibodies of IgM and IgG class to phenolic glycolipid-I (PGL-I) and to sonicated M. leprae components using ELISA and immunoblotting techniques, respectively. We had previously observed among a group of 11 armadillos, that some animals produced and maintained a high IgG antibody response to PGL-I. In this study, an animal's ability to produce and maintain an elevated IgG anti-PGL-I response was significantly correlated with their ability to delay dissemination of the infection and their ability to survive longer. When the animals were moribund, a significant decrease in the IgG anti-PGL-I absorbance value was observed. The detection of PGL-I in the plasma samples collected from moribund armadillos suggested that high concentrations of PGL-I in the plasma may have contributed to a drop in absorbance values by the formation of non-lattice-type immune complexes in vivo. As detected by immunoblotting, the IgM and IgG response to antigens derived from sonically disrupted M. leprae was directed towards molecules with broad bands of immunoreactivity ranging from 21- to 45-kDa. There were no distinguishing features of these antibody responses among armadillos as was evident with the IgG anti-PGL-I responses. PMID- 2215055 TI - Low-magnification electron micrography of leproma in human skin based on semithin and ultrathin sectioning. AB - Low-magnification electron micrography of leprosy lesions is described. The various cell types in the lesions, the relationships to leprosy bacilli and the distribution of bacilli in the lesions of lepromatous leprosy, are neatly demonstrated in the low-magnified pictures. PMID- 2215056 TI - Histoid lesion in nerve of a lepromatous patient. AB - This report pertains to a patient who had untreated diffuse lepromatous disease of 8- to 10-years' duration. Two peripheral nerves were beaded, which on biopsy showed histoid features. Because of its rarity, the case is reported. PMID- 2215057 TI - The anatomical distribution of single leprosy lesions in an African population, and its implications for the pathogenesis of leprosy. AB - Data on the anatomical sites of single leprosy lesions found in 635 newly diagnosed and biopsy-confirmed leprosy patients are presented. These patients were found during total population surveys carried out by the Lepra Evaluation Project, a prospective longitudinal study of the epidemiology of leprosy in Karonga District, Northern Malawi. There was a striking excess of single lesions on the face and the back of the arms, compared to the distribution of skin surface area, and a deficit on the legs, regardless of age. There is some evidence for a sex difference in lesion distribution among adults, with facial and arm lesions being relatively more common in females and back lesions being more common in males. The excess of lesions on the face compared to the lower limbs is similar to data from Uganda, but very unlike data from Burma and elsewhere in Asia. Overall, the distribution of lesions does not suggest a pattern reflecting entry of Mycobacterium leprae, nor does it suggest an association with anatomical distribution of the nervous or vascular system. It is argued that the distribution reflects the influence of some 'local' environmental or behavioural factors. PMID- 2215058 TI - Effect of treatment on immune responsiveness in lepromatous leprosy patients. AB - This study was performed in order to analyse whether the immune unresponsiveness to Mycobacterium leprae, largely seen in lepromatous patients, persisted after discharge from treatment. Lymphoproliferation and skin tests were performed using two mycobacterial antigens (M. leprae and BCG) in three groups of lepromatous patients grouped by treatment status. Forty-seven per cent of the lepromatous patients tested acquired reactivity to M. leprae after long-term treatment. PMID- 2215059 TI - Epidemiological pattern of leprosy in Ethiopia: a review of the control programmes. AB - Leprosy control started in a limited area of Ethiopia in 1956. Extended coverage of the country was achieved in the early seventies. Review of the data from the control projects since 1976 revealed that leprosy is a disease of the Ethiopian highlands where prevalence rates as high as 7 per thousand have been recorded in some provinces, while the cumulative national average for the last 13 years was 2.6 per thousand. The paucibacillary form was predominant. However, unlike other African countries, a relatively high proportion of multibacillary leprosy was found in Ethiopia. The male-to-female ratio was 2:1 with the highest prevalence in the 15-44 years age bracket. Detection rates for new cases have shown a gradual decline since 1982, a year before multiple drug therapy (MDT) was introduced into the country. For the last 5 years the number of new cases has stabilized at 4700/year. These trends probably reflect a general reduction in the prevalence of leprosy in the country, while the conspicuous decline in 1982 is most likely related to discharge of cases during screening before MDT. The new villagization policy of Ethiopia with its effective reorganization of the populations is believed to make control programmes and supervision of MDT easier and presumably more effective. Similarly, more reliable prevalence and incidence studies could be undertaken with success. PMID- 2215061 TI - New cases of leprosy in the Cross River Region, Nigeria. AB - Rates of leprosy cases newly reporting during 1986 are examined for a region of south-eastern Nigeria. Figures reveal that in the part of the region which was designated in 1987 as a new state, half of the administrative units had new case reporting rates higher than in adjacent areas, while the other half had very few cases reporting in 1986. Possible explanations are offered and the implications of the pattern for leprosy control in the new state are examined. PMID- 2215062 TI - Clofazimine-induced lymphoedema. PMID- 2215060 TI - Carvable silicone rubber prosthetic implant for atrophy of the first web in the hand. AB - Muscular atrophy of the first web space in the hand is a common finding following ulnar nerve palsy and this deformity is very stigmatizing among leprosy patients in some countries and cultures. We present our experience with the carvable soft silicone rubber block implant to correct this deformity. We discuss the procedure, results and advantages over other techniques. Fifteen operations were performed at the 'Lauro de Souza Lima' Research Institute, Bauru, Brazil during a period of six years. One complication was encountered due to an implant that was too large. The results were considered good in twelve instances and fair in three. PMID- 2215063 TI - Protective footwear for leprosy patients: a rapid method for the cutting out of sandal components. PMID- 2215064 TI - Protective footwear for leprosy patients with loss of sole sensation: locally made canvas shoes, deepened for a 10-MM rubber insert. PMID- 2215065 TI - Comment: the use of histopathology in leprosy diagnosis and research. PMID- 2215066 TI - Comment: value of thermal sensibility testing in leprosy diagnosis in the field- field trial of a pocket device. PMID- 2215067 TI - Comment: rifampicin pharmacology. PMID- 2215069 TI - Secretion of platelet-activating factor by periovulatory ovine follicles. AB - Secretion of platelet-activating factor (PAF) in vitro by ovine follicles and ovarian interstitium obtained at various times before, during and after the endogenous preovulatory surge of luteinizing hormone (LH) and ovulation was quantified by radioimmunoassay. Release of PAF by the preovulatory follicle increased within 2 h after initiation of the surge of LH. Capacity for secretion of PAF was greatest at the time of ovulation, then declined thereafter. Production of PAF by ovarian interstitium throughout the periovulatory period was relatively low and did not change with time. It appears that PAF could act as an intrafollicular mediator in the mechanisms of ovulation and(or) luteinization. PMID- 2215068 TI - N-substituted derivatives of 4-piperidinyl benzilate: affinities for brain muscarinic acetylcholine receptors. AB - N-Substituted derivatives of 4-piperidinyl benzilate were synthesized and their affinities for central muscarinic cholinergic receptors determined using an in vitro radioligand binding assay. 4-Piperidinyl benzilate exhibited a Ki value of 2.0 nM. N-Substitution with a methyl or an ethyl group increased the affinity to 0.2 nM, whereas substitution with a n-propyl or isopropyl group decreased the binding affinity over 100 fold. Compounds with aralkyl substitutions at the nitrogen atom of piperidinyl benzilate were also synthesized and evaluated. The Ki values (nM) obtained for these compounds were: benzyl, 0.2; p-nitrobenzyl, 13.0; p-fluorobenzyl, 3.0; phenethyl, 8.0; p-nitrophenethyl, 15.0. These data suggest that a binding region near the piperidinyl nitrogen may tolerate bulky aromatic substitutions (e.g., benzyl or phenethyl) as well or better than straight chain or branched alkyl substitutions (e.g., n-propyl or isopropyl). PMID- 2215071 TI - Effect of a synthetic platelet activating factor on steroidogenesis of cultured porcine granulosa cells. AB - An embryo-derived platelet activating factor has been demonstrated to play an important role in reproduction. This report examined the effect of various doses of a synthetic platelet activating factor on the production of progesterone by porcine granulosa cells in culture. Granulosa cells aspirated from ovarian follicles of prepubertal gilts were grown for 24 hours in Dulbecco's Modified Eagles Media: Ham's F-12 with 5% fetal bovine serum and 1 micrograms/ml insulin. Cells were washed once in serum-free media and then cultured for an additional 48 hours with 0 to 5000 ng/ml of the platelet activating factor in media containing either 0.25% bovine serum albumin or 1% fetal bovine serum. Cells grown with fetal bovine serum produced 50% of the amount of progesterone that was produced in the absence of serum. Low doses of the platelet activating factor caused a slight decrease in progesterone production. Higher doses (greater than 500 ng/ml) in serum-free media caused a marked decrease in progesterone production. Serum had a protective effect at high doses of platelet activating factor which was probably mediated by enzymatic degradation of the platelet activating factor. In summary, platelet activating factor had no stimulatory effect on production of progesterone by porcine granulosa cells in culture. PMID- 2215070 TI - Prevention of immunosuppression in stressed mice by neurotropin(NSP). AB - It is well known that the immune function can be compromised by stress. To investigate immune function in mice stressed by experimental restraint or unavoidable and opioid dependent stress, we evaluated the changes in total body weight and in organ weights (liver, spleen and thymus) of these animals, as well as the phagocytic activity of macrophages, the cytotoxicity of T cells and inhibitory effects on tumor growth and changes in T cell subset populations. At the same time we evaluated the effects of Neurotropin (NSP), a substance extracted from the inflamed skin of rabbits inoculated with the vaccinia virus and which appears to possess neuroimmunomodulating activity. The experimentally stressed group exhibited a reduction of phagocytic activity of macrophages, cytotoxicity of T cells and inhibitory effects on tumor growth. In addition there were changes in the population of T cell subsets. In those animals pretreated with NSP, the immunosuppression induced by stress was ameliorated. As compared with several agents which influence phagocytosis, neurotropin exhibited effects similar to that of agents that blocked the adrenaline receptor and an opioid antagonist rather than tranquilizer (diazepam) and a cholinergic receptor blocker. The pharmacologic effects of neurotropin support a relationship between the actions of the central nervous system and the immune system. PMID- 2215072 TI - Antibodies to morphine in workers exposed to opiates at a narcotics manufacturing facility and evidence for similar antibodies in heroin abusers. AB - According to the International Narcotics Control Board, over 45,000 kg of morphine and 54,000 kg of codeine were ethically manufactured in 1986 at three facilities in the United States. Little information exists about possible adverse health effects associated with workplace exposure to opiate compounds in this industry. Because there are no specific federal standards for workplace exposure to narcotic dusts, exposure-control defaults to the nuisance dust standard (10 mg/m3, as an 8 hr time-weighted average). Narcotics manufacturing workers were evaluated for anti-morphine IgG before and 10 mo. after the implementation of an improved respiratory protection program (RPP). Significantly elevated IgG levels were measured before the improved RPP (P less than 0.005). After the improved RPP, a significant reduction was observed (P less than 0.001), suggesting that specific antibody levels could be used as biomarkers of exposure. Inhibition studies showed that the antibodies were specifically directed against morphine with some cross reactivity with morphine derivatives. Preliminary results are also shown which indicate that similar anti-morphine antibodies are present in the sera of intravenous heroin abusers. Elevated levels (P less than 0.05) of anti-morphine antibodies were detected in sera from heroin abusers, providing evidence that similar antibodies may be produced from non-occupational exposure to opiates. These finding have potentially far-reaching implications for addiction research and drug testing. PMID- 2215073 TI - Hypoglycemic action of Salvia lavandulifolia Vahl. spp. oxyodon:a contribution to studies on the mechanism of action. AB - Having previously demonstrated the hypoglycemic action of Salvia lavandulifolia Vahl, subspecies oxyodon, the mechanism of action was further investigated. The hypoglycemic action may be the result of several synchronous mechanisms: a) potentiation of insulin release induced by glucose, b) increased peripheral uptake of glucose, c) decreased intestinal absorption of glucose and d) hyperplasia of the pancreatic islet beta cells (seen after chronic treatment). PMID- 2215074 TI - Brain corticotropin-releasing factor acts as inhibitor of stress-induced gastric erosion in rats. AB - Gastric lesions are known to be caused by stress. Corticotropin-releasing factor (CRF) is a key peptide initiating various stress response. This study was designed to investigate how brain CRF is involved in the occurrence of stress induced gastric erosion in rats. Intracerebroventricular (icv) administration of CRF suppressed the occurrence of gastric erosion induced by water-immersion restraint stress, and its suppressive effect was blocked by coadministration of a CRF receptor antagonist in rats. The peripheral administration of CRF had no influence on the occurrence of erosion. The icv administration of a CRF receptor antagonist or anti-rat CRF gamma-globulin increased gastric erosion induced by the stress. Ganglionic blockade with chlorisondamine, muscarinic blockade with atropine, or bilateral adrenalectomy by itself significantly inhibited the occurrence of stress-induced gastric erosion, and no additional effect of CRF on these treatments-induced inhibition of erosion was found. These results, therefore, suggest that the occurrence of stress-induced gastric erosion is mediated by the autonomic nervous system- and adrenal-dependent pathway, and that brain CRF reduces the occurrence of stress-induced gastric lesions by acting on its specific receptor within the central nervous system, probably through the autonomic nervous system- and adrenal-dependent mechanism. PMID- 2215075 TI - Dietary fat-induced changes in protein and carbohydrate selection are not explained by alterations in neuronal membrane fatty acid composition. AB - We previously showed changes in protein and carbohydrate selection in response to qualitative differences in dietary fat. Alterations in macronutrient selection were specifically related to changes in dietary saturated fat, but not to relative or absolute differences in dietary essential fatty acids. Three experiments were conducted to determine if changes in specific fatty acids in bulk phase neural membranes were associated with differences in macronutrient selection. For each experiment, specific fatty acid profiles were achieved by blending dietary fat sources. Rats consumed 20% (w/w) fat diets varying only in their fatty acid composition. After 2 weeks, rats were challenged with a selection paradigm. Each experiment showed a significant effect of dietary fat on neural membrane fatty acid composition (p less than 0.05) and alterations in individual fatty acids were correlated with changes in dietary fatty acids (p less than 0.05). However, dietary fat had no consistent effect with respect to which particular neural membrane fatty acids were modified, and there was no correlation between changes in specific membrane fatty acids and macronutrient selection. These findings suggest that alteration of specific fatty acids in bulk phase neural membranes do not mediate macronutrient selection behavior. PMID- 2215076 TI - Phosphorylation of chicken growth hormone. AB - The possibility that chicken growth hormone (cGH) can be phosphorylated has been examined. Both native and biosynthetic cGH were phosphorylated by cAMP-dependent protein kinase (and gamma -32P-ATP). The extent of phosphorylation was however less than that observed with ovine prolactin. Under the conditions employed, glycosylated cGH was not phosphorylated. Chicken anterior pituitary cells in primary culture were incubated in the presence of 32P-phosphate. Radioactive phosphate was incorporated in vitro into the fraction immunoprecipitable with antisera against cGH. Incorporation was increased with cell number and time of incubation. The presence of GH releasing factor (GRF) increased the release of 32P-phosphate labelled immunoprecipitable GH into the incubation media but not content of immunoprecipitable GH in the cells. The molecular weight of the phosphorylated immunoreactive cGH in the cells corresponded to cGH dimer. PMID- 2215077 TI - Interaction between lipids and bovine brain calmodulin: lysophosphatidylcholine induced conformation change. AB - We have monitored the interaction of several lipids with the bovine brain calmodulin(CaM) and analyzed the effect of lysophosphatidylcholine(lyso-PC, 2-50 micrograms/ml) on conformation of CaM and the interaction between CaM and CaM binding protein(CaMBP), using a fluorescence signal of 1 (dimethylamino)naphthalene-5-sulfonate-labeled CaM(DNS-CaM). Lyso-PC(egg, 20 micrograms/ml), among various natural lipids including phosphatidylserine(PS), phosphatidylinositol(PI), phosphatidylethanolamine (PE) and their lyso forms, greatly and dose-dependently enhanced the intensity of DNS fluorescence of DNS CaM in the presence (100 microM CaCl2) and absence (1 mM EGTA) of Ca2+. Apparent dissociation constants calculated from the fluorometric titrations of binding of lyso-PC to DNS-CaM were 0.6 and 3.7 micrograms/ml in the presence and absence of Ca2+, respectively. Lyso-PC remarkably prevented both trypsin-induced quenching of the fluorescence of DNS-CaM and tryptic digestion of native CaM in the absence of Ca2+. Enhancement of DNS fluorescence of DNS-CaM by CaMBP was observed only in the presence of Ca2+ and lyso-PC could further increase the fluorescence intensity of the complex. These all results suggest that lyso-PC can modulate the interaction between CaM and CaMBP as a result of its direct effect on conformation of CaM. PMID- 2215078 TI - Injected tryptophan increases brain but not plasma tryptophan levels more in ethanol treated rats. AB - In previous studies, long term treatment with ethanol has been shown to enhance brain 5-hydroxytryptamine 5-(HT) metabolism by increasing the activity of the regulatory enzyme tryptophan hydroxylase and or availability of circulating tryptophan secondarily to an inhibition of hepatic tryptophan pyrrolase. In the present study ethanol treatment given for two weeks decreased hepatic apo tryptophan pyrrolase but not total tryptophan pyrrolase activity in rats. Tryptophan levels in plasma and brain did not increase significantly. But there was a marked increase of 5-HT but not 5-hydroxyindoleacetic acid (5-HIAA) concentration in brain, suggesting a possible increase in the activity of tryptophan hydroxylase. The effect of a tryptophan load on brain 5-HT metabolism was therefore compared in controls and ethanol treated rats. One hour after tryptophan injection (50 mg/kg i.p.) plasma concentrations of total and free tryptophan were identical in controls and ethanol treated rats, but the increases of brain tryptophan 5-HT and 5-HIAA were considerably greater in the latter group. The results are consistent with long term ethanol treatment enhancing brain serotonin metabolism and show that brain uptake/utilization of exogenous tryptophan is increased in ethanol treated rats and may be useful to understand the role and possible mechanism of tryptophan/serotonin involvement in mood regulation. PMID- 2215079 TI - Effect of acute ethanol on beta-endorphin secretion from rat fetal hypothalamic neurons in primary cultures. AB - To characterize the effect of ethanol on the hypothalamic beta-endorphin containing neurons, rat fetal hypothalamic neurons were maintained in primary culture, and the secretion of beta-endorphin (beta-EP) was determined after ethanol challenges. Constant exposure to ethanol at doses of 6-50 mM produced a dose-dependent increase in basal secretion of beta-EP from these cultured cells. These doses of ethanol did not produce any significant effect on cell viability, DNA or protein content. The stimulated secretion of beta-EP following constant ethanol exposure is short-lasting. However, intermittent ethanol exposures maintained the ethanol stimulatory action on beta-EP secretion for a longer time. The magnitude of the beta-EP response to 50 mM ethanol is similar to that of the beta-EP response to 56 mM of potassium. Ethanol-stimulated beta-EP secretion required extracellular calcium and was blocked by a calcium channel blocker; a sodium channel blocker did not affect ethanol-stimulated secretion. These results suggest that the neuron culture system is a useful model for studying the cellular mechanisms involved in the ethanol-regulated hypothalamic opioid secretion. PMID- 2215080 TI - Effect of age on contractile response to angiotensin II in rat aorta. AB - The effects of aging on contractile response to angiotensin II and tachyphylaxis to it were investigated using aortic strips from rats aged 1.5, 4 and 22 months. Whether the endothelium was present or not, the contractile response to angiotensin II was greater and tachyphylaxis to it was less in 1.5-month-old rats than in 4- and 22-month-old rats. The differences between 4- and 22-month-old rats were not significant. Removal of the endothelium enhanced angiotensin II induced maximal contraction and depressed the tachyphylaxis, these endothelial effects being greater in 4- rather than in 1.5-month-old rats. When the contractile force of angiotensin II was adjusted to a similar level for 1.5- and 4-month-old rats, the endothelial effect on the tachyphylaxis was greater in the 4-month-old rats, but no significant difference was noted in the endothelial effect on the contractile force. These results suggest that during growth, the contractile response of rat aorta to angiotensin II decreases while the endothelial effect on it increases. PMID- 2215081 TI - Brain and cerebrospinal fluid uptake of zidovudine (AZT) in rats after intravenous injection. AB - Uptake kinetics of zidovudine into cerebrospinal fluid (CSF) and brain tissue were determined in adult Sprague Dawley male rats after single intravenous injection of 6.7 mg/kg (25 mumol/kg). The drug kinetics in plasma followed biexponential disposition with an initial distribution half-life of approximately 11 minutes and an elimination half-life of 40 minutes. Over the plasma concentration range of 0.2 to 10 micrograms/ml, the cerebrospinal fluid to plasma ratio averaged 14.8 +/- 1.9% whereas the mean brain tissue to plasma ratio was 8.2 +/- 1.2% (uncorrected) or 2.3 +/- 1.8% (corrected) for the brain vascular space contribution. Simultaneous nonlinear regression analysis of brain, CSF and plasma concentration data indicate that the overall rate constant for efflux of drug from brain is approximately 75-fold higher and from CSF is 8-fold higher than the respective rate constants for influx. Thus, the ratio of the efflux to influx appears to be the predominant factor in determining the net accumulation of drug into CSF and brain parenchymal tissue. PMID- 2215082 TI - Depletion of cardiac norepinephrine but not brain catecholamines by MPTP-N-oxide in mice. AB - After a single dose in mice, MPTP-N-oxide caused a dose-dependent depletion of cardiac norepinephrine which was similar although less pronounced than that caused by MPTP itself. After repeated daily doses, MPTP-N-oxide depleted cardiac norepinephrine, but did not deplete norepinephrine in the frontal cortex or dopamine in the striatum of mice. MPTP-N-oxide differed from MPTP, which depleted cardiac norepinephrine, cortical norepinephrine and striatal dopamine after repeated daily doses, but was similar to MPP+, another metabolite of MPTP, which depleted only cardiac norepinephrine. These data suggest that MPTP-N-oxide may contribute to the peripheral catecholamine-depleting effects after MPTP injection. PMID- 2215083 TI - The effect of SCH 23390 against toxic doses of cocaine, d-amphetamine and methamphetamine. AB - The effect of SCH 23390, a dopamine-one (D1) antagonist, in preventing acute toxicity induced by lethal doses of cocaine, d-amphetamine, and methamphetamine was studied in the rat. Animals were first pretreated with SCH 23390 (0.0, 0.5, 1.0, and 2.5 mg/kg, i.p.) and then were challenged with cocaine (70 mg/kg, i.p., an LD85), d-amphetamine (75 mg/kg, i.p., an LD95), and methamphetamine (100 mg/kg, i.p., an LD90). SCH 23390 did not alter the incidence of stimulant-induced seizures compared to the vehicle controls. Significant protection against cocaine induced death was afforded only by the lowest dose of SCH 23390 tested. Significant protection against d-amphetamine-induced death was provided by all doses, with a dose dependent effect noted so that the incidence decreased from 95% for vehicle to 30% (p less than or equal to 0.01) with 2.5 mg/kg SCH 23390 pretreatment. No statistically significant reduction in the incidence of methamphetamine-induced death was seen with SCH 23390 pretreatment. The ability of SCH 23390 to protect against d-amphetamine, but apparently not against methamphetamine-induced death, suggests that different mechanisms of toxicity may exist between these drugs at high doses. PMID- 2215084 TI - Acetylcholine release detected by trans-striatal dialysis in freely moving rats correlates with spontaneous motor activity. AB - In vivo acetylcholine (ACh) release from the anterior, middle, or posterior striatum and the level of spontaneous motor activity were determined simultaneously using trans-striatal dialysis in freely moving rats. Spontaneous ACh release from the middle striatum was higher than from either the anterior or posterior striatum and correlated with the level of spontaneous motor activity. These findings indicate that drug-induced striatal ACh release could be modified by changes of the level of motor activity in freely moving rats. PMID- 2215086 TI - Hydrolysis of fluorescent pyrene-acyl esters by human pancreatic carboxylic ester hydrolase and bile salt-stimulated lipase. AB - Fluorescent esters containing pyrenedecanoic acid (P10) or pyrenebutanoic (P4) acid (P4cholesterol, P10cholesterol, P4- and P10-containing triacylglycerols) were synthesized and used as substrates for human pancreatic carboxylic ester hydrolase and bile salt-stimulated lipase from human milk. Both enzymes were purified by immunoaffinity chromatography. All fluorescent pyrene derivatives were hydrolyzed by pancreatic carboxylic ester hydrolase and bile salt-stimulated lipase, but at different rates. The hydrolytic rates of the "short" acyl esters (P4-containing esters) were higher than those of the "long" ones (P10-containing esters). Conditions were optimized for sensitivity of the assay using fluorescent cholesteryl esters. The pH optimum was 7.5-8.0. Sodium cholate exhibited a stronger activating effect than taurocholate or taurodeoxycholate (maximal activation was achieved with 5 mmol/L cholate and with a molar ratio cholesteryl ester/cholate around 1:10). Both pancreatic carboxylic ester hydrolase and bile salt-stimulated lipase from milk were strongly inhibited by the other amphiphiles tested, namely phosphatidylcholine and Triton X-100, and were inactivated by low concentrations (10 mumol/L) of the serine-reactive diethyl-paranitrophenyl phosphate (E600). Both enzymes were strongly inhibited by relatively low concentrations of plasma low density lipoproteins. These studies indicate that the fluorescent esters containing pyrene fatty acids can be used as substrates for assaying and investigating the properties of pancreatic carboxylic ester hydrolase as well as bile salt-stimulated lipase from milk. PMID- 2215087 TI - The association of lysophosphatidylcholine with isolated cardiac myocytes. AB - The ability of exogenous lysophosphatidylcholine to produce electrophysiological derangements and cardiac arrhythmias in the heart has been documented. The action of lysophosphatidylcholine is thought to be mediated via its association with the membrane. The present study examined the nature of the association of lysophosphatidylcholine with isolated rat myocyte membrane. The association was studied by incubating myocytes in a lysophosphatidylcholine-containing medium. The association of lysophosphatidylcholine with the myocyte sarcolemma was not affected by palmitic acid and glycerophosphocholine but was reduced by platelet activating factor (PAF). The addition of albumin (5 mg/mL) at the end of the incubation period effectively removed the lysophosphatidylcholine from the myocytes. Our results suggest that most of the lysophosphatidylcholine in isolated myocytes was associated preferentially with the outer leaflet of the myocyte sarcolemma. This type of association might be responsible for the lysophosphatidylcholine-induced electrophysiological alterations in the heart. PMID- 2215088 TI - Influence of dietary linoleic acid and trans fatty acids on the fatty acid profile of cardiolipins in rats. AB - Cardiolipins (CL) have unique fatty acid profiles with generally high levels of polyunsaturated fatty acids, primarily 18:2n-6, and low levels of saturated fatty acids. In order to study the effect of dietary fatty acid isomers on the fatty acid composition of cardiolipins, rats were fed partially hydrogenated marine oils (HMO), rich in 16:1, 18:1, 20:1, and 22:1 isomeric fatty acids, supplemented with linoleic acid at levels ranging from 1.9% to 14.5% of total fat. Although the dietary fats contained 33% trans fatty acids, the levels of trans fatty acids in CL were below 2.5% in all organs. The fatty acid profiles of cardiolipins of liver, heart, kidney and testes showed different responses to dietary linoleic acid level. In liver, the contents of 18:2 reflected the dietary levels. In heart and kidney, the levels of 18:2 also paralleled increasing dietary levels, but in all groups fed HMO, levels of 18:2 were considerably higher than in the reference group fed palm oil. In testes, the 18:2 levels were unaffected by the dietary level of 18:2 and HMO. PMID- 2215085 TI - Lipids in gap junction assembly and function. AB - Gap junctions (GJ) are important regulators of cellular function. They provide channels for the direct movement of small molecules between cells and thus control cell-to-cell transfer of metabolites and the transmission of various stimuli. Gap junctions have been shown to be involved in a multitude of cellular processes ranging from cell synchronization and neuronal function to cell differentiation and carcinogenesis. Much knowledge has been gained in recent years concerning the structure and molecular organization of GJ proteins; yet, the mechanisms that control and modulate gap junction assembly and function are still not well understood. Although it is quite apparent that the GJ proteins assemble in the lipid milieu of the plasma membrane, and that the cluster of proteins assembled in the junction do function in a lipid environment, there is a general paucity of information on the role of lipids in the gap junction assembly process and in the function of gap junctions. The present review is a comprehensive account of current knowledge on gap junction lipids. We also discuss what is known to date on the involvement of lipids in gap junction formation. Special emphasis is being placed on the potential role of membrane cholesterol in gap junction assembly and function. PMID- 2215089 TI - Synthesis and characterization of cytochrome P-450 epoxygenase metabolites of eicosapentaenoic acid. AB - Eicosapentaenoic acid, a major component of fish oil extracts, was recently shown to be metabolized to vicinal diol regioisomers by renal and hepatic cytochrome P 450 epoxygenases. The diol products were also found in the urine of people ingesting fish oil. In the present report, we developed a chemical method of making milligram amounts of the epoxide intermediates and their diol products. Eicosapentaenoic acid was reacted with 0.1 eq. m-chloroperoxybenzoic acid for 15 min. After normal- and reverse-phase high performance liquid chromatography plus capillary gas chromatography and electron impact mass spectrometry, the products were identified as 17,18-cis-epoxy-eicosa-5,8,11,14-tetraenoic, 14,15-cis-epoxy eicosa-5,8,11,17-tetraenoic, 11,12-cis-epoxy-eicosa-5,8,14,17-tetraenoic, 8,9-cis epoxy-eicosa-5,11,14,17-tetraenoic and 5,6-cis-epoxy-eicosa-8,11,14,17-tetraenoic acids. The total epoxide yield from eicosapentaenoate was 10% per incubation. By reincubating (cycling) the unused substrate 10-20 times, the total epoxide yield could be increased to 66-88%. Epoxide regioisomers were not produced in equal amounts; epoxygenation was facilitated as the distance between the target double bond and carbomethoxy group increased. Upon hydrolyzing the epoxides, the gas chromatographic retention times and mass spectra of the diol products were found to match those of biological metabolites. In addition, each of these standards was rapidly and quantitatively synthesized in an amount (milligram) adequate for biological tests. PMID- 2215092 TI - Streaming liver. VI: Streaming intra-hepatic bile ducts. AB - Thirty male adult rats, weighing 250-300 g, were injected with 0.5 muCi [3H] thymidine. The rats were killed in groups of five, at the following times: 1 h, 14, 30, 60, 90 and 120 days. The livers were fixed in formalin, embedded in paraffin and cut into 5-microns-thick sections, which were then dipped into liquid emulsion for autoradiography. Bile ducts were evaluated in all portal tracts of a section. Obliquely cut bile ducts were excluded. The number of cells paving the duct lumen was defined as bile duct class. Class is roughly proportional to bile duct size. One hour after labelling, labelling index was 3.39 +/- 0.06% (the second number is one standard error of the mean). With time it declined, reaching 0.22 +/- 0.15 on day 60. Initially labelled cells were found in narrow bile ducts and the mean labelled cell was located at class 7.48 +/- 0.63. With time, labelled cells proceeded into wider bile ducts advancing daily 0.122 +/- 0.025 classes. Intra-hepatic bile duct epithelium renews its cells continuously in the same way as epidermis or gastro-intestinal mucosa do. It consists of two kinetic compartments, a progenitor (P) and a functional (Q) compartment. P feeds Q with cells. PMID- 2215091 TI - Mouse strain differences in susceptibility to sporidesmin-induced biliary tract injury. AB - Biliary tract injury was examined in four inbred strains of mice orally dosed with 500 micrograms of the fungal toxin sporidesmin. Semiquantitative histological analysis was used to assess the grade of necroinflammatory changes in the gall bladder, intra- and extrahepatic biliary tree and lobular parenchyma. Injury was greatest in the C57BL/6 and C3H strain mice and was least in SJL/J mice. In these strains injury was greatest at 4 days and had regressed by 10 days. In BALB/c mice the damage, although similar to that in SJL/J mice at 4 days, persisted at the same severity at day 10 and was accompanied by periductal fibrosis and occasionally by obliteration of ducts typical of sclerosing cholangitis. Analysis of the time-course of development of the lesions in C57BL/6 mice showed that the primary target for the toxin is the biliary epithelium. The severity of the lesions within the liver increased centripetally and the worst affected ducts were found at the confluence of the lobar ducts with the common bile duct. The variation in the degree of damage and rate of healing between strains may be due to differences in sporidesmin excretion in bile or interactions with biliary epithelial cells and/or efficacy of protective cellular repair mechanisms. PMID- 2215090 TI - Uptake, incorporation and metabolism of (3H)triolein in the isolated perfused rabbit heart. AB - The purpose of these experiments was to study the uptake and metabolism of exogenous triglyceride in the isolated perfused rabbit heart. When infused into the rabbit heart, [9,10-3H(N)]triolein was retained and incorporated into a lipid fraction that had the chromatographic mobility of authentic triolein. Incorporation of labeled triolein was not likely to be the result of a lipoprotein lipase-mediated lipolysis/resynthesis cycle, since: (i) The distribution of radioactivity following administration of [3H]oleic acid was markedly different from the distribution of radioactivity following the administration of [3H]triolein; (ii) heparin was administered to the rabbits at the time of sacrifice; and (iii) the hearts were perfused with a protein-free buffer for 20 min prior to the labelling period. When isoproterenol was administered to hearts labelled with [3H]triolein, there was an increased output of total radioactivity, composed of labelled free fatty acids, diacylglycerol and monoacylglycerol. In these same hearts, there was an increased output of glycerol in response to isoproterenol. However, following the administration of bradykinin or angiotensin II, neither the radioactivity nor the glycerol content of the perfusate was changed. These data suggest that [3H]triolein is selectively incorporated into the triglyceride pool of the isolated perfused rabbit heart. Furthermore, this [3H]triolein is available to hormonally-activated lipolytic enzymes. PMID- 2215093 TI - Surecut 0.6 mm liver biopsy in the diagnosis of cirrhosis. AB - Liver biopsy with the 0.6 mm (23 gauge) Surecut needle was compared to conventional Menghini biopsy in the diagnosis of cirrhosis. Seventy-seven consecutive patients (mainly alcoholics) with a clinical indication for liver biopsy had both biopsies performed simultaneously. In 71 patients sufficient material for a morphological diagnosis concerning liver architecture was obtained with both biopsy techniques (Surecut insufficient in 5 cases and Menghini insufficient in 2 cases). The biopsies were classified as cirrhosis or non cirrhosis. There was agreement in 69 cases (97%, confidence limits 90-100%). Using the result of the Menghini biopsy as the final diagnosis, the predictive values for a positive and negative diagnosis for the Surecut needle were 96% and 98%, respectively. There were no complications to either of the biopsies. It is suggested that the 0.6 mm Surecut biopsy may be used in the diagnosis of cirrhosis in cases where conventional Menghini needle biopsy is contraindicated. PMID- 2215094 TI - Liver disease among Polish alcoholics. Contribution of chronic active hepatitis to liver pathology. AB - A group of 70 chronic alcoholics--65 men and 6 women--has been studied. HBsAg was found in 11 (16%), and at least one marker of HBV infection was present in sera from 31 (44%) persons, these results being significantly higher than in a matched control population. The commonest single histological patterns were: steatosis (18 cases), and alcoholic hepatitis (18 cases), followed by normal liver (14 cases) and chronic active hepatitis (12 cases). Cirrhosis was diagnosed in only 4 cases. Five cases of chronic active hepatitis could be attributed to infection with HBV or HDV; in the remaining 7 cases the etiology was unclear. Infection with HBV seems to play an important role as the cause of liver disease among alcoholics in Poland, and chronic active hepatitis of various etiology may be an important form of liver pathology among them. PMID- 2215095 TI - Liver damage in juvenile inflammatory bowel disease. AB - During a 12-year period, 46 children and adolescents with inflammatory bowel disease were followed from the time of diagnosis with regular biochemical tests of liver function. Thirty-four patients had ulcerative colitis and 12 had Crohn's disease. Mean age at the time of diagnosis was 10.2 years (range 7 months-17 years) and the mean follow-up period was 5.2 years (range 1-11 years). Pathological liver function tests were found in 60% of the 34 patients with ulcerative colitis: 9 of these 20 patients demonstrated more severe disturbance, usually at the time of diagnosis. Liver damage was most frequent in patients with total colitis. Liver biopsy was performed in eight patients, demonstrating "pericholangitis", fibrosis and in one case cirrhosis. Morphometry of electron microscopical pictures revealed a significantly increased number of lysosomes and dilated cisternae of the rough endoplasmic reticulum. ERCP was performed in two patients, verifying primary sclerosing cholangitis in one. Four of the 12 patients with Crohn's disease had mildly pathological liver function tests. No correlation was found to the extent, duration or treatment of bowel disease. In our series of juvenile inflammatory bowel disease, liver damage occurred frequently, especially in ulcerative colitis. The more severe changes tended to coincide with the onset of bowel disease. PMID- 2215096 TI - Integrity of the cytoskeletal system is important for phagocytosis by Kupffer cells. AB - The mechanism of phagocytosis by Kupffer cells is believed to involve the Ca2(+) calmodulin system. However, the role of myosin in this system is still unknown. In this study, we found that myosin light chain kinase inhibitor (ML-9) inhibited phagocytosis by cultured Kupffer cells using polystyrene beads, a time-lapse VTR system and fluorescent staining techniques. The inhibitory effects of ML-9 suggest that myosin may be involved in this complex cellular function and that the integrity of the cytoskeletal system is essential for normal phagocytosis. PMID- 2215097 TI - Study of plasma neuropeptide Y (NPY) and catecholamines levels during spinal anesthesia. AB - Plasma levels of neuropeptide Y (NPY) and catecholamines were investigated during spinal anesthesia. Ten ASA physical status I-II patients were studied after obtaining institutional approval and informed contents. All patients were free from endocrine and metabolic disease underwent elective low risk operation. No premedication was given before operation. Spinal anesthesia was performed on lateral position from L3-4 interspace with 15 mg tetracaine without added epinephrine. The analgesic level was about at T6 dermatone. Blood samples were obtained from radial artery catheter, 15 minutes before spinal anesthesia and 5', 15', 30', 60', 120', during operative period and 30' after operation in postanesthesia recovery room. The results showed that there were significant elevation in plasma level of NPY during spinal anesthesia compared with the level before anesthesia. However, no statistically significant changes of plasma catecholamines were found. PMID- 2215098 TI - Suppression of hemodynamic change before extubation--lidocaine through modified endotracheal tube. AB - Twenty females, aged 31 to 49 years, scheduled for abdominal total hysterectomy were randomly divided into two groups in this study. An epidural catheter was placed at T11-12 before general anesthesia. All patients receive the combination of epidural anesthesia and general anesthesia for the operation and relief of pain postoperatively. The modified endotracheal tube we used is shown in Fig. 1. For patients in group I (Lidocaine group), 2 mL 4% lidocaine solution was injected through the catheter to desensitize the tracheal mucosa around the cuff after the surgeon had removed the uterus. In group II (Control group), no special management was made. All patients were not extubated until they were considered to be awake. Systolic blood pressure at three and one minute before extubation and pulse rate recorded at one minute before extubation showed in patients of group I were statistically smoother than those recorded in group II (p less than 0.01). All patients had gag reflex just after awake extubation. PMID- 2215099 TI - Activation of epileptogenic activities by etomidate in electrocorticoencephalography (ECoG) during operation for epilepsy. AB - Epileptic surgery is a radical and ablative treatment for medically refractory epilepsy. Electrocorticoencephalography (ECoG) obtained by subdural strip electrodes should always be used during operation for precise localization of epileptic focus and mapping the extent of its involvement. But difficulties and ambiguities exist when the patient's ECoG is suppressed, either owing to the anticonvulsant used, being at the stage of posterictal period, or the effects of anesthetics during operation. Then, intentional activation of epileptogenic activity should be performed to locate the pathological focus in order to accomplish a successful surgical treatment. Etomidate has been considered as an abnormal electroencephalogram (EEG) activator and its use is not recommended in patients with epilepsy. But lesser dose of etomidate as an activator for ECoG has not been investigated. The study reported here established that etomidate as an hypnotic has not only anesthetic properties but, paradoxically, also activates epileptogenic activity. With the latter pharmacologic characteristic, etomidate can be used to deliberately activate the spikes of the potentially epileptogenic tissue, the delineation and localization of which may help the surgeon determine to what extent the pathological cortex be resected in surgical treatment of a refractory epilepsy. The current recommended dosage of etomidate at veterans General Hospital-Taipei for ECoG in epileptic surgery is 0.1-0.15 mg/kg/iv. PMID- 2215100 TI - Early detection of cerebral dysfunction by quantitative EEG during cardiopulmonary-bypass period for open-heart surgery. AB - Neuropsychiatric complications are well known risks of open heart surgery. In this regard cerebral damage is caused either by microembolism or insult from low perfusion pressure as a consequence of extracorporeal circulation. It seems probable that monitoring of the quantitative electroencephalography (QEEG) during the surgical procedure can help minimize the incidence of neurological sequelae through early detection. Moreover, it seems important to establish whether the pre-operative EEG has a predictive value for the possible neurological outcome and whether the post-operative EEG has conclusive value for the neurological outcome and, above all to ascertain whether the peri-operative QEEG contains information valuable on the diagnosis of final neurological outcome. To elucidate the feasibility of QEEG as a means to monitor the cerebral function a study was thus undertaken. Twenty-five ASA II-IV patients with age ranging from 25-79 y/o undergoing cardiac surgery under extracorporeal circulation were enrolled for study. The types of surgery varied from coronary artery by-pass graft (CABG), valvular replacement, and excision and grafting for aortic dissecting aneurysm. 16-channel EEGs were recorded with a Cadwell Spectrum 32 in accordance with the international 10-20 system. 48 epochs (1 epoch = 2.5 seconds) of EEG recordings of pre-bypass and post-bypass periods were measured and quantitatively analyzed. Pre- & post-operatively, psychoneurological assessments were performed and correlated with the QEEG. The parameters employed in the study were absolute power, relative power, power asymmetry, and coherence. All the results of two session comparisons were transformed into z score values. Our preliminary study revealed that there exists a specific multivariate profile of QEEG for specific disease entity. And all the patients with z score less than or equal to 3.0 turned out to be free from any significant sequelate. PMID- 2215101 TI - [Dose-response relationships of propofol in Chinese]. AB - Propofol is a new intravenous anesthetic which possesses the rapid induction and recovery of anesthesia. It has been approved to be used in clinical anesthesia and critical care medicine since 1989. From the dose-response study of propofol, we can get the ED50 and induction dose of propofol and compare those with other anesthetics. Sixty young patients, ASA I-II, both sexes, were allocated into six groups of ten patients. All of patients did not receive premedicants. Groups I-VI were given intravenously over 25 sec 1.0 mg/kg, 1.2 mg/kg, 1.4 mg/kg, 1.6 mg/kg, 1.8 mg/kg and 2.0 mg/kg, respectively. Blood pressure and heart rate were monitored and recorded before and 1 min, 3 min, 5 min after the injection of propofol. Induction of anesthesia by propofol is considered to be successful as a patient closes his eyes and does not response to simple command. As a patient obeys the order to open his eyes, he is judged to emerge from anesthesia. Induction and recovery times were recorded in each successfully-induced patient. Data were analyzed using Litchfield and Wilcoxon, and Student's t tests. The ED50 of propofol was found to be 1.46 mg/kg (95% confidence interval: 1.35 mg/kg to 1.58 mg/kg). Induction and recovery times at 1.0 mg/kg, 1.2 mg/kg, 1.4 mg/kg, 1.6 mg/kg, 1.8 mg/kg and 2.0 mg/kg were 40 sec and 5.6 min, 38 sec and 6.0 min, 38 sec and 6.2 min, 36.8 sec and 6.7 min, 36.3 sec and 7.2 min, 35.5 sec and 7.2 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2215102 TI - Sacroepidural analgesia for post-operative pain relief in children. AB - For evaluation of the practicality of epidural analgesia for alleviation of post operative pain, 66 class I or II patients with age ranging from 6 months to 12 years undergoing elective surgical procedures below the lower abdomen were enrolled for study during the period from January to April 1989. Before termination of general anesthesia a single dose of 0.25% bupivacaine, respectively at 0.25 mL/kg (Ideal body weight), 0.5 mL/kg, 0.75 mL/kg, 1.0 mL/kg and 1.25 mL/kg was given sacroepidurally to 5 groups of patients. Our results showed that for surgery below the lower abdomen a dose at 1.0 mL/kg was sufficient to suffice the need for relief of post-operative pain. At this dosage it achieved a neural block up to T8-T6 and provided with an analgesia that could last 6.0 +/- 2.1 hours. During the entire course there were no untoward effects such as hypotension, bradycardia, vomiting and shivering to come about. Therefore, sacroepidural analgesia with 0.25% bupivacaine at fitting single dose is safe and feasible in children as far as relief of post-operative pain for procedures below the lower abdomen is concerned. PMID- 2215103 TI - [Infusion speed as a factor to influence the analgesic level of spinal anesthesia -hypobaric solution of tetracaine]. AB - In spinal anesthesia, as known, the injection speed of local anesthetic drug is a factor which influences the analgesic level. For study it, automatic infusion apparatus was available to control as 5 kinds of infusion speed (0.02-0.51 mL/s), and 78 patients were divided into 6 groups. The results of the painless level was discussed by T-test and distribution analysis (F-test). The mean of painless level in each group was found to be no significant difference as discussed by T test. But the largest distribution was found in the group of 0.04 mL/s, and high analgesic level as rise up to T6 was occasionally found in groups of 0.04 mL/s & 0.02 mL/s. It means, the infusion speed is not an important factor, but extremely slow infusion is more dangerous than high speed infusion, which will take a risk of high level spinal anesthesia. PMID- 2215104 TI - Rectal ketamine versus intranasal ketamine as premedicant in children. AB - The effects of ketamine administered per nasus (PN) or per rectum (PR) as pre anesthetic medication for day surgery was studied in 70 ASA class I children with age ranging from 6 months to 6 years. Before study they were divided into 3 groups. Group A (n = 25) received no premedicant, while group B (n = 25) and group C (n = 20) received ketamine 6 mg/kg PR and 3 mg/kg PN as premedicant respectively. It was demonstrated that patients in group B and group C accepted the facemask during induction of anesthesia more willingly and peacefully than those in group A. In group B and group C there was accompaniment of analgesic effect seen postoperatively. The incidence of adverse reactions (nausea, vomiting, laryngospasm, salivation, respiratory depression) was low following the use of PR or PN ketamine although the children in these two groups emerged more belatedly from anesthesia and stayed in the post-anesthetic recovery room (PARR) for a longer time than in group A. PMID- 2215105 TI - Cardiovascular responses to tracheal intubation after thiopentone or propofol. AB - The hemodynamic responses to laryngoscopy and intubation were compared in forth patients of ASA class I-II undergoing various surgical procedures without premedication were randomly divided into two groups and given propofol (2.5 mg/kg) or thiopentone (5 mg/kg) for induction, and succinylcholine (1.5 mg/kg) for facilitating laryngoscopy and intubation. Each group consisted 20 patients. Baseline data has no significant difference between the two groups. After induction systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) heart rate (HR), cardiac output (CO), cardiac index (CI) were all lower in the propofol group than thiopentone group. It indicate that propofol (2.5 mg/kg) has more cardiovascular depressive effects than thiopentone (5 mg/kg). Local injection pain was complained by every patient. PMID- 2215106 TI - Intrathecal morphine's effect on somatosensory impulses transmission-studied with posterior tibial nerve SSEP. AB - In order to investigate neurotoxic potential of spinally injected morphine solution, somatosensory evoked potential (SSEP) was utilized to detect the change of electrophysiologic activity of spinal neurons after long term application of intrathecal morphine. Eight patients received intrathecal morphine injection regularly after CHEMO-PORT implantation were studied with posterior tibial nerve SSEP. Patients received SSEP examination just before and right after first episode of morphine injection and were followed up at 30 minutes, 60 minutes, 2 hours, 8 hours, and the 7th day and the third month of regularly injection. The results showed that there were no definite change of latencies and amplitudes of impulses generated by lumbar spinal cord (N22) and cortex (P40). We therefore suggest that electrophysiologic activities of spinal cord and cortex are not affected by chronic intrathecal morphine injection. Possible mechanism and proposed pathway of morphine's action were also discussed. PMID- 2215107 TI - Simple management of poor cervical progression during labor by continuous epidural analgesia. AB - A series of 112 primiparous parturients in labor with poor cervical progression were managed according to the double-lined labor nomogram. These patients all had labor progression beyond the alert line which were defined as poor cervical progression. Continuous low concentrated marcaine (0.125%) epidural analgesia were then offered to these indicated patients. These 112 poor labors were compared with 143 poor cervical progression labors without epidural analgesia in terms of mode of delivery and maternal morbidities. The results showed a decrease in cesarean section rate in cases with epidural analgesia (20.5% vs 34.3%, p less than 0.05) but no increase use of instrumentation was noted, also, maternal morbidities were much less in epidural cases compared to poor labors without epidural analgesia (6 in 112 vs 19 in 143, p less than 0.05). Continuous epidural analgesia performed on labors with poor progression improved the labor outcome and decrease maternal morbidities satisfactorily. PMID- 2215108 TI - Epidural anesthesia for spine surgery. AB - Over the last 2 years, the authors have had experience with epidural anesthesia for a variety of spine operations in 20 patients. It is proved to be safe, reliable, and effective. Perioperative complications were minimal and could be easily treated. No patient had a new neurologic deficit as a result of the epidural technique. Thus, epidural anesthesia should not be excluded from the anesthesiologist's consideration simply because of the presence of spine disease or neurologic deficit. PMID- 2215109 TI - [Cerebral infarction after resection of epidermoid carcinoma of buccal mucosa under general anesthesia--report of one case]. AB - A 60 year-old hypertensive male was operated with resection of epidermoid carcinoma of buccal mucosa. He was expired postoperation complicated with left middle cerebral artery infarction. The cerebral infarction may be induced by acute hypotension, improper position during operation and underlying disease associated with old age. Prevention methods included preoperative evaluation, immediately injection vasopressor when acute hypotension occurred during anesthesia, and avoidance of improper position to compress vertebral or carotid artery which may leading to cerebral perfusion insufficiency. PMID- 2215110 TI - Unexpected high level of epidural analgesia during labor--report of one case. PMID- 2215111 TI - Increased sensitivity to atracurium in a child with Duchenne's muscular dystrophy. PMID- 2215112 TI - Intraoperative malignant hyperthermia--report of one case. PMID- 2215113 TI - A suspicious malignant hyperthermia--report of one case. PMID- 2215114 TI - [Transfusion-induced severe allergic reaction--report of one case]. AB - Recently, improved cross-matching techniques have reduced the frequency of adverse reactions of blood transfusion less the 2%, but allergic reactions (non hemolytic) occur in about 3% of patients receiving properly typed and crossmatched blood. Allergic reactions to blood or drugs administered during anesthesia represent an unpredictable and occasionally life-threatening event. When a severe allergic reaction develops, an aggressive and prompt treatment, including intravenous epinephrine, is necessary to minimize morbidity and mortality. We experienced a case of intraoperative shock due to blood transfusion. The case manifested with hypotension, tachycardia, cutaneous rash and bronchospasm during blood transfusion and then the aggressive treatment was given to resume normal vital signs. The rest of anesthesia and surgery as well as the recovery was uneventful and the patient was discharged on the 18th postoperative day. PMID- 2215115 TI - Treatment of intra-operative penile tumescence--report of six cases. PMID- 2215116 TI - Acute upper airway obstruction secondary to the retropharyngeal bleeding after pharyngeal punch biopsy. PMID- 2215117 TI - Necrotizing enterocolitis. Part II. Treatment and nursing care. PMID- 2215118 TI - [The clinical quality evaluation of radiopharmaceutical preparations for diagnostic use]. AB - The authors issued some recommendations for assessment of new radiopharmaceuticals (RP) at the stage of clinical trials. The most decisive thing is to determine the clinico-diagnostic efficacy of a radiopharmaceutical and its safety. Direct extrapolation of the results of experimental investigation of biodistribution of labeled compounds on man was shown to be fraught with serious errors. Differences in RP pharmacokinetics necessitate a planned, methodologically correct and clinically substantiated study of a RP in selected groups of patients taking into account the functional purpose of a drug. The assessment of RP quality is based upon a study of functional suitableness resulting from pharmacokinetic data and the determination of optimum methodological conditions and safety of a new RP, including the calculation of radiation a patient is exposed to during a diagnostic procedure. The stages of clinical trials are given in detail, their unification is aimed at raising their quality and improved clinical assessment of a RP. PMID- 2215119 TI - Analexia nervosa: coping with the medical literature. PMID- 2215120 TI - Donations wanted for Soviet-American Exchange Program. PMID- 2215121 TI - Input technology. PMID- 2215122 TI - Coding: why and how. AB - Codes are used in every aspect of our daily lives, and many of the coding schemes in use are inappropriate, poorly implemented, or too fragmented in their coverage. This paper describes various approaches to coding, pointing out their strengths, weaknesses, and most appropriate applications. Those attempting to set up a coding scheme are strongly advised to analyze their needs, select the approach that is best for the application at hand, and carefully monitor the implementation of the coding system they choose. Only by understanding and monitoring our coding schemes can we minimize the amount of inappropriate and exasperating codes in our daily lives. PMID- 2215123 TI - Choosing an office computer: preliminary steps. PMID- 2215124 TI - CD-ROM products from CMC ReSearch. PMID- 2215125 TI - The seventh annual directory of medical hardware and software companies. PMID- 2215126 TI - Coding diagnoses with a microcomputer. PMID- 2215127 TI - Estimated creatinine clearance. PMID- 2215128 TI - [The prevention of fatigue in young children]. PMID- 2215129 TI - [The problems of sex education among students]. PMID- 2215130 TI - [The work experience of a general hospital]. PMID- 2215131 TI - [The use of phonophoresis with ophthalmic drug films of apilak]. PMID- 2215132 TI - [The characteristics of managing a repeat pregnancy and labor in women with a history of eclampsia]. PMID- 2215133 TI - [Posttraumatic keratitis]. PMID- 2215134 TI - [Cysts of the kidneys]. PMID- 2215135 TI - [Sinusoidal modulated currents in the combined rehabilitation of patients after operations on the stomach for peptic ulcer]. PMID- 2215136 TI - [The laser therapy of duodenal peptic ulcer in children]. PMID- 2215137 TI - [Echoencephalography in clinical practice]. PMID- 2215138 TI - [Patient care in a hemodialysis ward]. PMID- 2215139 TI - [Static diseases of the foot]. PMID- 2215140 TI - [The characteristics of the work of the nurse anesthetist when patients are admitted with severe combined trauma]. PMID- 2215141 TI - [Therapeutic procedures in diseases of the ear, nose and throat]. PMID- 2215142 TI - [Recipe cards on dietary dishes]. PMID- 2215143 TI - [The incompatibility of antihistamine preparations with other drug agents]. PMID- 2215144 TI - [Deontology in dental practice]. PMID- 2215145 TI - [Sof'ia Stepanovna Shcherbatova]. PMID- 2215146 TI - [What the nurse should know about working with children's parents]. PMID- 2215147 TI - [Against tobacco smoke]. PMID- 2215148 TI - [The healthy life style office]. PMID- 2215149 TI - [The prevention of road traffic traumatism]. PMID- 2215150 TI - [The personality characteristics of nurses that influence the quality of their work activities]. PMID- 2215151 TI - [Nurses in the front ranks of the "Health for All" movement]. PMID- 2215152 TI - [Postoperative treatment in Dupuytren's contracture]. PMID- 2215153 TI - [The optimal form for the use of narcotic preparations in a general hospital]. PMID- 2215154 TI - [The work experience of the geriatrics department of a psychiatric hospital with the rendering of care by the Moscow Church of Evangelical Christian Baptists]. PMID- 2215155 TI - [Eye involvement in toxocariasis]. PMID- 2215156 TI - [Skin lesions as a reaction to the development of malignant tumors of the internal organs]. PMID- 2215157 TI - [Modern transfusion science and the paths for its further development]. PMID- 2215158 TI - [Care of the oral cavity in treating mandibular fractures]. PMID- 2215159 TI - [The acute schizophrenic attack]. PMID- 2215160 TI - [Recipe cards for dietetic dishes]. PMID- 2215161 TI - [The clinical picture and treatment of lesions caused by scorpion fish venom]. PMID- 2215162 TI - [Patient preparation for general anesthesia]. PMID- 2215163 TI - [The prevention of AIDS in therapeutic institutions]. PMID- 2215164 TI - [The use of vitamins in respiratory organ diseases in children]. PMID- 2215165 TI - [Smoking shortens human life]. PMID- 2215166 TI - [A perfusion apparatus for extracorporeal purification of the blood]. AB - Requirements for modern perfusion equipment intended for extracorporeal blood clearance are reviewed and possible trends in the improvement of the equipment in the BP-02 perfusion unit are defined. In that unit, one- or two-needle perfusion is maintained by a gearless drive, microprocessor control, concentrated data representation on a linear display in tabular form, and self-adjustment of the arterial and venous pressure control. PMID- 2215167 TI - [The technical requirements of simulating cardioplegia and perfusion of an isolated heart]. AB - A testing unit for simulating cardioplegia and restorative perfusion of an isolated heart is described. The testing unit is fitted out with a chamber for an isolated heart, an oxygenator, a heat exchanger, the perfusion system and organs controlling heart work under different conditions of perfusion and cardioplegia. The system approximates the physiological condition of the experiment and allows changing and controlling them on a broad enough scale. PMID- 2215168 TI - [Characteristics of the work of blood membrane oxygenators with porous membranes]. PMID- 2215170 TI - [Methodology of choosing blood-compatible biomaterials in vitro for artificial organs]. PMID- 2215169 TI - [Choosing the structure of the control system for an external counterpulsation complex]. AB - The paper is concerned with the principles of choosing the structure of the external counterpulsation control on an a.c. hydrodrive. An autonomous control mode and the control principles using a specialized microprocessor as well as computer-aided feedback control have been investigated. PMID- 2215171 TI - [Medical and technical aspects of replacing the lost functions of internal organs]. PMID- 2215172 TI - [Hemodiafiltration with preparation of the replacement solution using a dialysis apparatus without volumetric control of ultrafiltration]. AB - The authors describe a method of hemodiafiltration with preparing the replacement solution from dialysis liquid by means of the AK-10 apparatus (Gambro Company, Sweden) and a sterilizing hemofilter. The studies attest to the high efficacy and safety of the procedure. An opportunity is provided of increasing the replacement velocity, with the rate of filtration being stable and even reduced, which is of paramount importance in cases of unstable hemodynamics. Such a scheme enables one to simplify the procedure and decrease the cost of hemodiafiltration, thus forming the basis for its broad-scale application. PMID- 2215174 TI - [A portable, movable pneumatic drive for an artificial heart with an autonomous electrochemical source of energy]. AB - The authors have designed a pneumatic drive, which differs from the known ones in that it contains two electromagnetic two-linear and two-positioned air distributors while the motor operates in the mode excluding the change of its axis direction. This affords using a standard crank mechanism as a transformer of rotary motion to translational motion and reducing several times the power consumed. Besides, the two-linear and two-positioned air distributors allow a possibility of exercising a separate control over the time of the systole diastole phases of the left and right ventricles. In this case both ventricles can work at 100% filling whereby maintaining the capacity of the artificial heart without additional energy consumption. PMID- 2215173 TI - [The control and regulation of gas exchange in membrane oxygenators of the MOST 122 stationary type during open heart surgery]. AB - A system of controlling the perfusion parameters and the efficacy of extracorporeal gas exchange is described. The system has been developed and employed for the control and regulation of gas exchange in the MOST-122 oxygenators manufactured in the USSR and based on selective composition membranes. The system allows an expeditious assessment of gas exchange disorders which may occur during AC and extracorporeal oxygenation as well as their high accuracy correction, reaching optimal modes of ventilation. PMID- 2215176 TI - [The AIK-6.06 (ISL-6) artificial circulation apparatus]. PMID- 2215175 TI - [Results of test-bed and clinical trials of DIP-03-02 dialyzers manufactured by the West German firm Frezenius using polysulfone hollow fibers]. AB - The authors provide the results of the clinical trial of the dialyzers DIP-03-02 manufactured by the USSR in cooperation with the FRG (Frezenius Company). In accordance with clearances of low-, medium- and high-molecular compounds as well as with the ultrafiltration characteristics, DIP-03-02 are similar to the modern capillary dialyzers from hollow fibers on the basis of cellulose membranes with an analogous surface. During manufacture of the dialyzers DIP-03-02, the polysulfone membrane possessing low permeability for liquid was obtained for the first time. The tentative data on biocompatibility (the complement activation test) are positive. PMID- 2215177 TI - [The EUS-8-1 Uterostim-1 electrostimulator]. PMID- 2215178 TI - [The BP-02 perfusion unit]. PMID- 2215180 TI - [The technical requirements for artificial life support systems]. AB - The author advances a summarized concept of the bioartificial organism consisting of an operator, equipment and biological medium. Formulates the principle of man made life support, reviews a model of the bioartificial organism and a classification of processors that ensure the control of the physiological status of the biological medium. PMID- 2215179 TI - [A modification of the x-ray diagnostic units based on Roentgen-40 and manufactured by the Sevkavrentgen plant]. PMID- 2215181 TI - [Thermodynamic principles and physiologic criteria for the use of heat engines to drive the ventricles of an artificial heart]. AB - The authors review the thermodynamic bases and physiological limitations of the applicability of thermal engines for driving artificial heart ventricles. Show that the thermodynamic characteristics of Stirling and Brighton cycles do not make it possible to effectively use cycle-based engines in the artificial heart. A steam engine operating in accordance with the Rankine cycle may be regarded as an optimum type engine for that purpose. Demonstrate that according to the rules of physiology, use should be made of a separate driving of artificial heart ventricles by two independently operating steam engines. Provide the characteristics of the Soviet artificial heart "MIKRON" acceptable for implantation into the orthotopic position. PMID- 2215182 TI - Anti-adhesive activity of human casein against Streptococcus pneumoniae and Haemophilus influenzae. AB - The casein fraction of human milk was found to inhibit the attachment of Streptococcus pneumoniae and Haemophilus influenzae human respiratory tract epithelial cells. The inhibitory activity for S. pneumoniae remained after heat and trypsin treatment of the casein and was found in oligosaccharides released from casein. kappa-Casein, which is the most highly glycosylated casein component, inhibited pneumococcal attachment at concentrations similar to the whole casein fraction. The results are consistent with the known recognition of GlcNAc beta 1-3Gal by S. pneumoniae, since human milk and bovine colostrum, which contain GlcNAc, inhibited attachment, but mature bovine milk lacking GlcNAc did not. The effect on H. influenzae was similar to that on S. pneumoniae in that the attachment was inhibited by human casein and bovine colostrum, but not by either mature bovine milk or by the bovine casein fraction. The kappa-casein component of human milk was a less efficient inhibitor of H. influenzae attachment than the whole casein fraction and the free oligosaccharides were inactive. This anti microbial effect of human casein represents a new mechanism for the protection by breast-milk against respiratory tract infection. PMID- 2215183 TI - Covalent linkage between the capsular polysaccharide and the cell wall peptidoglycan of Streptococcus pneumoniae revealed by immunochemical methods. AB - The attachment of capsular polysaccharide to Streptococcus pneumoniae was examined using monoclonal and polyclonal antibodies. Among the strains examined, the capsular polysaccharide of types 2, 4, 6A, 6B, 7F, 8, 14, 19F and 23F was bound to the pneumococci whereas that of a type 3 strain was not. Sequential treatment with 2% SDS at 100 degrees C, pronase, and EDTA did not dissociate the capsular polysaccharide from the pneumococci. Treatment of the cells with mutanolysin, a muramidase that degrades the cell wall peptidoglycan of pneumococci and other streptococci, released both the capsular and the cell wall C-polysaccharide (C-Ps). Type 6A capsular polysaccharide released from cell walls by mutanolysin treatment, was fractionated by high performance liquid chromatography and examined by immunoelectrophoresis. It was found to be bound to both the C-Ps and the peptidoglycan. The bond between the capsular polysaccharide and the peptidoglycan has not yet been identified but is probably covalent, as the two components could not be dissociated after boiling in SDS. Based on our studies with type 6A, we propose that capsular polysaccharide and C-Ps of the pneumococcus are linked to the peptidoglycan at different sites and, thereby, indirectly to each other. Studies in mice showed that the peptidoglycan enhanced the serum antibody response to C-Ps but not to type 6A polysaccharide. PMID- 2215184 TI - Yersinia enterocolitica serotype O:3 is arthritogenic for mice. AB - It is shown, for the first time, that Yersinia enterocolitica serotype O:3 is experimentally arthritogenic. Moreover, it is arthritogenic for the mouse, an optimal model for human yersiniosis. This arthritis can be induced by the oral route, the most common route in man. The pattern of joint disease closely parallels that of human reactive arthritis associated with this pathogen. PMID- 2215185 TI - An in vivo method for studies of traumatic vasospasm. AB - A study was undertaken to develop a model for investigations of traumatically induced vasospasm. The left ear of the rabbit was denervated under short anesthesia. With the animal under light sedation, spasm of the central ear artery was repeatedly induced with a clip applying forceps. To evaluate the vasospasm, the vessel was transilluminated with cold light, and the internal diameter was continuously measured. The spasm was assessed in terms of its duration, intensity (reduction of initial diameter) and severity (integrated change in diameter over time). Repetitive application of the forceps on the same vessel segment shortened the spasm duration. With prolonged pinch duration, the spasm duration was lengthened. The preparation was stable for at least 3 hours. This model was effective for manipulating small vessels and producing spasm and is of potential value for studying the treatment of vasospasm by topical local intra-arterial and systemic methods. PMID- 2215186 TI - Vasodilator action of prostaglandin E1 on microcirculation of rat cremaster muscle. AB - Vascular spasm is often present after microsurgical procedures, and its presence or absence can greatly influence the success rate of such operations. Prostaglandin E1 (PGE1) is known to be a potent vasodilator and antiaggregator of small blood vessels. Using intravital videomicroscopy in the rat cremaster model, this study visually and quantitatively monitored changes in vessel diameter to observe the effect of PGE1 on the microcirculation and compared its action with that of 1% lidocaine. The results suggest that PGE1 (10 micrograms/ml) can significantly relieve epinephrine-induced vasoconstriction at the terminal arteriole, arteriole, and small artery level (vessel diameters 10-50 microns). The vasodilatory action of PGE1 is reflected by an increase in vessel diameter, and PGE1 may have a role in reversing vascular spasm after microsurgery, enhancing the survival rate of replanted extremities. PMID- 2215187 TI - Time of low-dose acetylsalicylic acid administration influences in vivo platelet function and thrombus formation following arteriotomy and intimectomy; an experimental study in small arteries of rabbits. AB - To investigate if low-dose acetylsalicylic acid (ASA), 4 mg/kg b.w., infused peroperatively or 10 hours preoperatively has antithrombotic effects, the central arteries of rabbit ears were prepared and 32P-labeled platelets injected. Arteriotomy and intimectomy were performed and blood flow was restored. Bleeding times at the sites of arteriotomy/intimectomy, in vivo accumulations of isotope labeled platelets, amounts of red thrombotic material, and patency were recorded. Bleeding times following arterial puncture and the effect of ASA on thromboxane production were studied separately. Ten hours after ASA administration, bleeding times were shortened at the sites of arteriotomy/intimectomy but were prolonged following arterial puncture. Platelet accumulations were lower in patent vessels in this group than in an untreated control group. Peroperative ASA treatment increased but treatment 10 hours prior to blood flow restoration did not significantly affect the number of occlusions. Thromboxane production in ASA treated rabbits is largely inhibited even 14 hours after administration. PMID- 2215188 TI - Soft tissue coverage of the hand with a free digital fillet flap. AB - A free digital fillet flap was used to achieve soft tissue coverage of the ulnar border of the hand in a 38 year old man with an industrial fan blade injury to the dominant hand. The use of a digital fillet flap from an unsalvageable ring finger allowed for a one-stage procedure avoiding donor site morbidity or need for additional reconstructive surgery. PMID- 2215189 TI - Angled side wall microarteriotomy scissors: a new end-to-side microvascular anastomosis instrument. AB - Creation of a smooth side wall arteriotomy for an end-to-side microsurgical anastomosis can at times be difficult and time consuming. To facilitate this maneuver, a new end-to-side microarteriotomy scissor was designed for creation of recipient vessel openings from 0.5-2 mm in size. These new scissors and their recommended use are described. PMID- 2215190 TI - Replantation 1990. PMID- 2215191 TI - Frontiers in microsurgery: replantation. PMID- 2215192 TI - Philosophy of replantation 1976-1990. PMID- 2215193 TI - Macroreplantation: an overview. PMID- 2215194 TI - Union Memorial Hospital experience with replantation: patterns of change. AB - The experience with replantation of amputated or devascularized parts of the upper extremity distal to the wrist was reviewed for 1976-1980 and again in a similar way for 1986-1989. Comparisons between the two groups were made to look for similarities and differences. Analysis of this experience may help treating physicians, patients, and third-party payers to make decisions about management of these injuries. PMID- 2215195 TI - Sensory recovery following digital replantation. AB - The recovery of sensibility following digital replantation is essential in the restoration of hand function. We reviewed 12 series of digital replantations between 1977 and 1989. Three hundred sixty-seven fingers and 87 thumbs were successfully replanted. Mean age was 32.5 years. Mean follow-up was 33.5 months. Mean static two-point discrimination (S2PD) was 9.3 mm in clean thumbs vs. 12.1 mm in crush/avulsion thumb replantations. Mean S2PD was 8 mm in clean finger vs. 15 mm in crush/avulsion finger replantations. Overall mean S2PD was 11 mm in thumb and 12 mm in finger replantations. Sixty-one percent of replanted thumbs and 54% of replanted fingers regained useful S2PD (less than 15 mm or greater than or equal to S3 +). Factors that influenced digital sensibility following replantation included patient's age, level and mechanism of injury, digital blood flow, cold intolerance, and postoperative sensory reeducation. Recovery of sensibility in the replanted digit is comparable to simple nerve repair and to nerve grafting techniques. Further emphasis should be on elucidating the mechanism of cold intolerance, which was a significant complaint for most replanted digits. The universal practice of postoperative sensory reeducation will continue to improve digital sensibility following replantation. PMID- 2215196 TI - One hundred eleven thumb amputations: replantation vs revision. AB - One hundred eleven patients who sustained isolated, complete thumb amputation between 1971 and 1985 were reviewed to assess results of replantation and to compare these with results of amputation revision. Routine postoperative evaluation was performed in 69 successful replant patients and in 42 with revision. Twenty-five of the replant group and 18 of the revision group returned for additional testing that consisted of interview and physical examination, test of activities of daily living, Jebsen test of hand function, and both static and dynamic testing on the BTE work simulator. Ninety percent of replantations were between the metacarpophalangeal (MCP) joint and the proximal third of the distal phalanx. Shortening averaged 11 mm, and range of motion was 42% +/- 28% that of the uninjured thumb. One-half of the patients could touch the MP of their ring finger, and one-fourth could touch the proximal interphalangeal (PIP) joint. Twenty-one percent had 7 mm or less two-point discrimination, and 38% had between 8 and 20 mm. Eighty percent of both groups were able to perform activities of daily living at 80% of their uninjured side. Grip strength was approximately 84% of that of the uninjured hand in each group. Lateral pinch averaged 68% +/- 26% of that of the normal side in the replant group and 91% + 9% in the amputation group. Work simulator assessment of lateral and three-point pinch was better in the revision group. Scores on Jebsen testing were slightly better for those with replanted thumbs, but in general neither replant nor revision patients functioned as well as did Jebsen's normals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2215198 TI - Techniques of bone fixation in replantation surgery. PMID- 2215197 TI - Microvascular anastomoses in replanted fingers: do they stay open? AB - Replantation of fingers is a well established procedure following traumatic amputation. Several studies have documented the functional results of replanted digits. Studies have not documented the long-term (greater than 5 yrs) patency of the microvascular anastomosis in the replanted digit. Duplex imaging, a combination of B-mode ultrasound and bidirectional Doppler ultrasound has been shown to visualize vessels 1 mm in diameter. Color enhancement of the ultrasound image is now possible. We evaluated 18 patients with 24 replanted fingers to assess vascular patency. A minimum of five years follow-up was required for inclusion in the study group. Examination showed a patent anastomosis in every case and a Digital-Brachial Index within normal limits in 71% of the digits. Microvascular anastomoses in vessels as small as 1 mm in diameter remain open as long as 11 years following completion. The sophisticated techniques of color enhanced Duplex imaging makes long-term evaluation of these procedures possible in a non-invasive and accurate fashion. The use of such imaging modalities will have an important role in the evaluation of replanted digits and microvascular procedures in general. PMID- 2215199 TI - [Evaluation of the nervous system in workers in the furnace and coal divisions of the coke-producing plants]. AB - 240 workers of coking plant exposed to noxious chemical compounds released at coke production and control group consisting of 76 persons including 48 workers without direct contact with coke production process and 28 randomly selected healthy subjects were examined. No characteristic syndrome of subjective changes was found in workers of productive sphere. However, defective neurological symptoms were more prevalent in this group as compared to the controls. The workers from the group exposed developed neurotic syndromes with vegetative disregulation symptoms two times more frequently than the controls. The changes in EEG were significantly more prevalent in the workers occupationally exposed. The prevalence of diffuse changes in EEG depended on the level of exposure to BaP. PMID- 2215200 TI - [Study of social acceptance of periodic examinations by machine industry workers]. AB - Social acceptance of periodical examinations was evaluated via a survey conducted among a group of 530 machine industry workers. A questionnaire for prophylactic examinations was used which was worked out at the Department of Epidemiology and Statistics of the Nofer Institute of Occupational Medicine in Lodz, with additional questions concerning the level of acceptance of a new medical examination mode. In order to determine the letter the subject area was limited to elicit an answer to a question whether a new examination instrument at a periodical check-up meets the needs of the workers. The paper discusses the method of the study, characteristics of the population examined, including age, occupational exposure and work strenuousness. The findings revealed that 96.8% of subjects had accepted the new mode of periodical examinations which allows a conclusion that the method satisfies the workers' expectations as they find it suitable for managing their health problems. It is suggested that the form of periodical examinations should be modified since those presently applied do not facilitate early diagnosis or comprehensive evaluation of workers' health conditions. PMID- 2215201 TI - [Rhythm disorders of basic bioelectric activity of the brain in alcoholism and exposure to carbon disulfide (CS2)]. AB - A visual and computer-assisted analysis was made of basic brain biological function in 45 EEG recordings of alpha waves alone or mostly alpha waves. The study revealed abnormal frequency of alpha waves in patients with chronic alcoholism (60%) and in people chronically exposed to carbon disulphide (73.4%). The abnormalities most probably reflect dysfunction of the CNS. PMID- 2215202 TI - [Biological testing of fibrogenic effect of dust from the "Gliwice" mine on the lung tissue]. AB - Animal study was carried out to determine biological aggressiveness of mining dust by means of pulmonary tests. Dust samples, 50 mg settled dust, a mixture from 3 different mine layers (sample A) and 50 mg dust collected by the gravimetric method from different mine layers (sample B) were administered in two respective test groups by a single intratracheal injection. Silica content, determined according to Polezhayev, was found to range from 4.6% (sample A) to 12.7% (sample B). In months 3 and 6 of the experiment lung content of hydroxyproline was determined following Stegemann. Biochemical tests for hydroxyproline content revealed highest increase in the lungs of Group 2 animals 6 months after the onset of the experiment (10.312 mg). Very similar result was obtained in Group 1, with injected settled dust mixture: hydroxyproline level amounted to 10.214 mg. Both sample A and sample B induced elevated level of lung hydroxyproline although silica content in dust sample differed considerably. The study revealed that the biological aggressiveness of settled dust was not proportionate to the content of pure silica. It is thought that increased fibrogenic potentials of the settled dust may have resulted from defected crystalline structure of silica due to the grinding of the mineral in a hand mill. PMID- 2215203 TI - [Chemical safety (III)--its prospects in Poland]. AB - The paper discusses principles of the chemical safety system to be introduced in Poland. It is thought that the system should be based on a doctrine comprising theoretical considerations, definitions of concepts and scope of activity. Moreover, the organizational and legal background of the future system was also considered. According to the main principle of the chemical safety system, any activity, involving the use of chemicals gives rise to a risk of adverse health and environmental effects. The numerical value that can be assigned to such risk ranges between 0 and 1. Thus an essential activity related to chemical safety seems to be the determination of a socially acceptable risk. Chemical safety has been defined as an environmental state where the chemical substances of different origin pose either no risk of adverse health and environmental effects or the risk whose level is socially acceptable. The chemical safety system aims at limiting or preventing the risk arising from the use of chemicals. It is suggested that the activities of the future system should be supervised by the National Coordinating Committee for Chemical Safety which would stimulate both the research work on risk assessment and management as well as other activities pertaining to chemical safety. PMID- 2215204 TI - [Evaluation of the need of specialization of physicians in the field of occupational medicine]. AB - Analysing the trends in obtaining specialization in occupational health during last 15 years an evident deterioration of formal qualifications of physicians employed in occupational health service (OHS) was observed. These data were confronted with the needs resulting both from the present model of workers health care as well as with those arising from ratification of ILO Convention No 161 of 1985. It was stated that discrepancy between the need for specialists and the actual possibilities of their training cannot be removed without radical reform of the Polish health care system in general and health service reform in particular. PMID- 2215205 TI - [Psychological effects of chronic exposure to organophosphate pesticides--review of the literature]. AB - One of the occupational hazards is exposure to organophosphorous pesticides in agriculture. With 8.5% of all occupational poisonings in Poland organophosphate poisonings hold one of the topmost positions. Organophosphorous chemicals induce inhibition of AChE activity thus leading to nervous system impairment. Chronic exposure does not bring about acute poisoning, however it produces various disorders within the system. Only a few studies on chronic exposure consider psychological dysfunctions as a possible effect. The parameters examined most frequently include short-term memory, learning, eye-hand coordination, reaction time in simple and complex reactions. The findings reveal impairments of these functions due to chronic exposure to organophosphates. However, in view of the limited samples of test groups the conclusions can only be tentative. PMID- 2215206 TI - [Protoporphyrin level in erythrocytes of workers in coke-producing plants]. AB - Peripheral blood samples from workers of a coke factory were examined to determine protoporphyrin content in erythrocytes and haemoglobin concentration. Statistically significant increase of protoporphyrin level was found in the coke factory workers, as compared with the control group whereas haemoglobin content was very similar in both the groups. The results indicate that the working environment of coke factory may induce protoporphyrin synthesis in erythrocytes as well as inhibit generation of iron porphyrins. PMID- 2215207 TI - [Effect of work in the coke-producing plant on the circulatory system of workers]. AB - 253 coke ++ plant workers employed for over 5 years were subject to examination. From among them 207 were exposed to very high concentrations of benzo-a-pyrene (BaP) and tar substances as well as to benzene, its homologues and carbon monoxide. However, none of these concentrations exceeded MAC value. Apart from routine medical examinations resting ECG was made and when necessary propranolol test, exercise test or even coronarography. In addition, polycardiographic and ultrasonocardiographic examinations were carried out. Comparing the results obtained in the group exposed with the controls it was found that arterial hypertension, coronary insufficiency and pathologic polycardiograms were more prevalent in the workers exposed. Chronic exposure to CO, BaP and smoking habit were considered to be factors exerting a deteriorating effect on cardiac muscle. PMID- 2215208 TI - Hepatic gene function in health and disease. PMID- 2215209 TI - Prospects for gene therapy of familial hypercholesterolemia. AB - Familial hypercholesterolemia is an inherited disease in humans that is caused by a deficiency in the receptor that mediates the internalization and degradation of low density lipoprotein. Patients that inherit two abnormal low density lipoprotein receptor alleles have severe hypercholesterolemia, advanced atherosclerosis, and life-threatening coronary artery disease that is refractory to conventional therapies. In this review, we discuss the prospects for gene therapy in the treatment of familial hypercholesterolemia. PMID- 2215210 TI - Integration host factor affects expression of two genes at the conjugal transfer origin of plasmid R100. AB - Integration host factor (IHF) binds to two sites near the origin of transfer of the conjugative antibiotic resistance plasmid, R100. DNase I footprinting shows that one site is immediately adjacent to oriT and the gene X promoter, and another is adjacent to the traM promoter. A third site, known only from retardation gels, is near the traJ promoter. The relative promoter activities of genes X, traJ and traM are reduced in himA mutants (IHF-), as measured by chloramphenicol-resistance assays. Transcript analyses by Northern blots showed a reduction in size of the principal gene X and traJ transcripts in the absence of IHF. PMID- 2215211 TI - Sequence of the peh gene of Erwinia carotovora: homology between Erwinia and plant enzymes. AB - Polygalacturonase (Peh) and other pectolytic enzymes play a crucial role in the maceration of vegetables by soft rot Erwinia spp. We have sequenced the peh gene of Erwinia carotovora subsp. carotovora, and identified its product as a precursor of molecular weight 42,639, and a mature protein of molecular weight 42,200. A putative KdgR-binding site was identified in the region 5' to the peh gene. The Peh protein showed significant homology with Peh from tomato. In addition, we have found homologies between pectin methylesterase and pectate lyase from Erwinia and their counterparts in tomato. These homologies are described, and their significance discussed. PMID- 2215212 TI - Structural analysis of the pehA gene and characterization of its protein product, endopolygalacturonase, of Erwinia carotovora subspecies carotovora. AB - A clone producing a polygalacturonase (EC 3.2.1.15) in Escherichia coli was isolated from a genomic library of Erwinia carotovora subspecies carotovora constructed in PUC18. The DNA segment carrying the corresponding structural gene, named pehA, contained an open reading frame (ORF) encoding a 402-amino-acid (aa) polypeptide with an Mr of 42,849. In E. carotovora the polygalacturonase was synthesized with a 26-aa cleavable signal peptide. The mature 376-aa PehA had a calculated Mr of 40,064 and a pl of 10.19. The pH optimum of the enzyme was about 5.5 and the temperature optimum was in the range 35-45 degrees C. Analysis of the reaction products of polygalacturonic acid hydrolysis indicated that the PehA protein is an endopolygalacturonase. No similarity was observed between the aa sequences of PehA and other pectic enzymes of erwinias. However, substantial similarity was detected within the C-terminal portions of PehA and a previously described tomato polygalacturonase, suggesting that the bacterial and eukaryotic polygalacturonases may have a common origin. PMID- 2215213 TI - Recent advances in peptide chain termination. AB - Peptide chain termination occurs when a stop codon is decoded by a release factor. In Escherichia coli two codon-specific release factors (RF1 and RF2) direct the termination of protein synthesis, while in eukaryotes a single factor is required. The E. coli factors have been purified and their genes isolated. A combination of protein and DNA sequence data reveal that the RFs are structurally similar and that RF2 is encoded in two reading frames. Frame-shifting from one reading frame to the next occurs at a rate of 50%, is regulated by the RF2 specific stop codon UGA, and involves the direct interaction of the RF2 mRNA with the 3' end of the 16S rRNA. The RF genes are located in two separate operons, with the RF1 gene located at 26.7 min and the RF2 gene at 62.3 min on the chromosome map. Ribosomal binding studies place the RF-binding region at the interface between the ribosomal subunits. A possible mechanism of stop-codon recognition is reviewed. PMID- 2215214 TI - Intron-associated splicing reactions in bacteriophage T4. AB - Group I introns are present in at least three bacteriophage T4 genes: td, nrdB and sunY. The transcription products of these three genes have similar intron consensus regions and secondary structures, which render them capable of guanosine-mediated in vitro autocatalytic splicing reactions. Moreover, it has been shown that the 245-amino-acid protein encoded in the td intron expresses an endonuclease that cleaves near the joining site for the two exons in the intron deleted thymidylate synthase gene. The intron-containing td gene is resistant to the enzyme. As in the case of other group I intron-containing genes that have been described in eukaryotes, which also encode site-specific endonucleases, the td intron is highly mobile and can insert into the intron-less td gene by a process initiated by endonuclease cleavage near the insertion site. Whether intron transposition reactions have any physiological significance to the phage, or represent an early imprint on the evolution of introns, remains to be determined. PMID- 2215215 TI - Homologous DNA sequences on the virulence plasmids of pathogenic Yersinia and Salmonella dublin lane. AB - Yersinia and Salmonella harbour plasmids that encode traits important for virulence, enabling both pathogenic genera to survive and grow in cells of the reticulo-endothelial organs during systemic infections. We have detected DNA homology between the Salmonella dublin virulence plasmid pSDL2 and the plasmids of the pathogenic Yersinia species pestis, pseudotuberculosis, and enterocolitica. Three regions of pSDL2 were found to share homology with the virulence plasmid pIB1 of Yersinia pseudotuberculosis. Two separate hybridizing segments mapped within the previously characterized 6.4 kb vir region of pSDL2 in the SalI B fragment. The third homologous region involved the replicon of pIB1, which hybridized to the SalI C2 fragment of pSDL2. The virulence plasmid pCD1 from Y. pestis showed similar homology with the three regions of pSDL2. Homologies to the vir and SalI C2 regions of pSDL2 were also found on plasmids from Yersinia enterocolitica serotypes 0:9, 0:3 and 0:5, 27. The discovery of separate homologous regions on the virulence plasmids of Salmonella and Yersinia suggests a distant evolutionary relationship. PMID- 2215216 TI - Analysis of three nodD genes in Rhizobium leguminosarum biovar phaseoli; nodD1 is preceded by noIE, a gene whose product is secreted from the cytoplasm. AB - In a strain of Rhizobium leguminosarum biovar phaseoli, three copies of the regulatory nodulation gene nodD were identified on the Sym plasmid and sequenced. Two were closely linked to each other and the third was near, but not adjacent, to the nodABC genes. Each of these nodD genes could correct the Nod- defect of a nodD mutant strain of R. leguminosarum biovar viciae on peas. A truncated form of nodD2 could also correct this mutant, indicating that the C-terminus of NodD2 is not needed for inducing activity. Upstream of nodD1 and in the same operon is a newly described gene, noIE, whose product appears to be exported into the periplasm. Close to nodD2 is another gene, noIP, with no known counterpart in other rhizobia. Both noIP and noIE-nodD1 are preceded by 'nod-box' sequences and, in the former case, there appear to be two tandemly repeated nod-box sequences. Mutations in each of the nodD genes and in the noIE and noIP genes did not abolish nodulation or nitrogen fixation on beans. PMID- 2215217 TI - Octanoylation of the lipoyl domains of the pyruvate dehydrogenase complex in a lipoyl-deficient strain of Escherichia coli. AB - The overexpression of a subgene encoding a hybrid lipoyl domain of the dihydrolipoamide acetyltransferase component of the pyruvate dehydrogenase complex of Escherichia coli has previously been shown to result in the formation of lipoylated and unlipoylated products. Overexpression of the same subgene in a lipoic acid biosynthesis mutant growing under lipoate-deficient conditions has now been shown to produce domains modified by octanoylation as well as unmodified domains. It was concluded from the mass of a lipoyl-binding-site peptide that the modification involves N6-octanoylation of the lysine residue (Lys244) that is normally lipoylated, and this was confirmed by the trypsin-insensitivity of the corresponding Lys244-Ala-245 bond, and the absence of modification in a mutant domain in which Lys244 is replaced by Gln. This novel protein modification raises interesting questions concerning the pathway of lipoic acid biosynthesis and the mechanism of enzyme lipoylation. PMID- 2215218 TI - The Min DNA inversion enzyme of plasmid p15B of Escherichia coli 15T-: a new member of the Din family of site-specific recombinases. AB - Plasmid p15B is a bacteriophage P1-related resident of Escherichia coli 15T-. Both genomes contain a segment in which DNA inversion occurs, although this part of their genomes is not identical. This DNA segment of p15B was cloned in a multicopy vector plasmid. Like its parent, the resulting plasmid, pAW800, undergoes complex multiple DNA inversions: this DNA inversion system is therefore called Min. The min gene, which codes for the p15B Min DNA invertase, can complement the P1 cin recombinase gene. The Min inversion system is thus a new member of the Din family of site-specific recombinases to which Cin belongs. The DNA sequence of the min gene revealed that Min is most closely related to the Pin recombinase of the e14 defective viral element on the E. coli K12 chromosome. Like other members of the Din family, the min gene contains a recombinational enhancer element which stimulates site-specific DNA inversion 300-fold. PMID- 2215219 TI - The identification, characterization, sequencing and mutagenesis of the genes (hupSL) encoding the small and large subunits of the H2-uptake hydrogenase of Azotobacter chroococcum. AB - The structural genes (hupSL) of the membrane-bound NiFe-containing H2-uptake hydrogenase (Hup) of Azotobacter chroococcum were identified by oligonucleotide screening and sequenced. The small subunit gene (hupS) encodes a signal sequence of 34 amino acids followed by a 310-amino-acid, 34156D protein containing 12 cysteine residues. The large subunit gene (hupL) overlaps hupS by one base and codes for a predicted 601-amino-acid, 66433D protein. There are two regions of strong homology with other Ni hydrogenases: a Cys-Thr-Cys-Cys-Ser motif near the N-terminus of HupS and an Asp-Pro-Cys-Leu-Ala-Cys motif near the carboxy-terminus of HupL. Strong overall homology exists between Azotobacter, Bradyrhizobium japonicum and Rhodobacter capsulatus Hup proteins but less exists between the Azotobacter proteins and hydrogenases from Desulfovibrio strains. Mutagenesis of either hupS or hupL genes of A. chroococcum yielded Hup- phenotypes but some of these mutants retained a partial H2-evolving activity. Hybridization experiments at different stages of gene segregation confirmed the multicopy nature of the Azotobacter genome. PMID- 2215220 TI - Strain specific variation of outer membrane proteins of wild Yersinia pestis strains subjected to different growth temperatures. AB - Three Yersinia pestis strains isolated from humans and one laboratory strain (EV76) were grown in rich media at 28 degrees C and 37 degrees C and their outer membrane protein composition compared by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Several proteins with molecular weights ranging from 34 kDa to 71 kDa were observed to change in relative abundance in samples grown at different temperatures. At least seven Y. pestis outer membrane proteins showed a temperature-dependent and strain-specific behaviour. Some differences between the outer membrane proteins of full-pathogenic wild isolates and the EV76 strain could also be detected and the relevance of this finding on the use of laboratory strains as a reference to the study of Y. pestis biological properties is discussed. PMID- 2215221 TI - Short- and long-term effects of azadirachtin A on development and egg production of Rhodnius prolixus. AB - Azadirachtin A was given through a blood meal to 4th-instar larvae and to adult females of Rhodnius prolixus. Development (ecdysis) and egg production were inhibited in a dose-dependent manner. Long-term experiments with subsequent four feedings on azadirachtin-free blood were performed with 4th-instar larvae and with adult females. Only in the low-dose azadirachtin larval groups (0.01 and 0.1 microgram/ml of blood), development was partially restored; after a single 1.0 microgram/ml treatment about 50% of the treated larvae were still alive 120 days later without any adult emergence. Similarly fed females had a dose-dependent lower survival and egg deposition rate. The results are discussed in relation to the mode of azadirachtin A action. PMID- 2215223 TI - Biomphalaria amazonica Paraense, 1966 in the state of Mato Grosso do Sul, Brazil (Mollusca, Pulmonata, Planorbidae). PMID- 2215222 TI - Monoclonal antibodies against brain neurosecretory A cells of Panstrongylus megistus inhibit moulting and egg production in triatomines. PMID- 2215224 TI - Report of an epidemic outbreak of tegumentary leishmaniasis in a coffee-growing area of Colombia. PMID- 2215225 TI - Standardization of the IL-1 comitogenic assay using thymocytes from LPS-sensitive mouse strains. PMID- 2215226 TI - Occurrence of molluscs in aquaria of ornamental fishes in Belo Horizonte, Minas Gerais, Brazil. PMID- 2215228 TI - Amazonian visceral leishmaniasis--distribution of the vector Lutzomyia longipalpis (Lutz & Neiva) in relation to the fox Cerdocyon thous (linn.) and the efficiency of this reservoir host as a source of infection. PMID- 2215227 TI - Human, canine and equine (Equus caballus) leishmaniasis due to Leishmania braziliensis (= L. braziliensis braziliensis) in the south-west region of Sao Paulo State, Brazil. PMID- 2215229 TI - Influence of Trypanosoma cruzi strain on the pathogenesis of chronic myocardiopathy in mice. AB - The murine model of chronic Chaga's myocardiopathy was developed in 201 inbred and outbred mice. The experimental groups consisted of 1st: 73 inbred AKR and A/J mice inoculated with one of the following Trypanosoma cruzi strains: Peruvian (Type I), 12 SF (Type II) or Colombian (Type III); 2nd: 128 outbred Swiss mice, chronically infected either with Type II or Type III strains isolated from human patients from different geographical areas. All T. cruzi strains were previously characterized by their morphobiological behaviour in mice and by isoenzymatic patterns. For the 1st group the inoculum was 5 x 10(4) for the Peruvian strain and 1 x 10(5) for the 12 SF and Colombian strains. In the 2nd group-Swiss mice the inoculum size varied from 2 x 10(4) to 2 x 10(5). The inbred animals were killed at a 3 time-point scale (90, 180 and 240 days) post-infection. The Swiss mice were killed from 180 to 660 days after infection. The evaluation of parasitemia and serology (xenodiagnosis and indirect immunofluorescent test) was performed. The incidence of macroscopic alterations of the heart and cardiac index were evaluated. Histopathological lesions of the myocardium were graded. The influence of T. cruzi strain on the intensity of cardiac lesions was evaluated by the Chi-square test; the incidence of inflammatory lesions and its relationship to the parasite strain was evaluated by the Fisher test. The influence of the duration of infection was evaluated by using the Gamma Coefficient of Kruskal and Goodman and its measure of significance. Slight to severe microscopic alterations occurred in 85% of the chronically infected mice. There were a clear predominance on the incidence and intensity of inflammatory and fibrotic alterations for the mice infected with Type III strains. Statistical analysis has shown significant differences among the infected groups, in the inflammatory and fibrotic lesions. Macroscopic alterations (right cavities dilatation and apex aneurism of left ventricle), differed in incidence according to mice strains; in Swiss and AKR mice, significant differences were seen in mice infected with different T. cruzi strains, but the A/J mice failed to show significant differences correlated with different parasite strains. The duration of infection, from 90 to 240 days, could not be correlated with the degree of lesions in the several groups. PMID- 2215231 TI - Biological control of Biomphalaria tenagophila (Mollusca, Planorbidae), a schistosomiasis vector, using the fish Geophagus brasiliensis (Pisces, Cichlidae) in the laboratory or in a seminatural environment. AB - In order to investigate a possible method of biological control of schistosomiasis, we used the fish Geophagus brasiliensis (Quoy & Gaimard, 1824) which is widely distributed throughout Brazil, to interrupt the life cycle of the snail Biomphalaria tenagophila (Orbigny, 1835), an intermediate host of Schistosoma mansoni. In the laboratory, predation eliminated 97.6% of the smaller snails (3-8 mm shell diameter) and 9.2% of the larger ones (12-14 mm shell diameter). Very promising results were also obtained in a seminatural environment. Studies of this fish in natural snail habitats should be further encouraged. PMID- 2215230 TI - Prevalence of human T cell leukemia virus-I (HTLV-I) antibody among populations living in the Amazon region of Brazil (preliminary report). AB - Forty-three (31.4%) out of 137 serum samples obtained from two Indian communities living in the Amazon region were found to be positive for HTLV-I antibody, as tested by enzyme-linked immunosorbent assay (ELISA). Eighty-two sera were collected from Mekranoiti Indians, yielding 39% of positivity, whereas 11 (20.0%) of the 55 Tiriyo serum samples had antibody to HTLV-I. In addition, positive results occurred in 10 (23.2%) out of 43 sera obtained from patients living in the Belem area, who were suffering from cancer affecting different organs. Five (16.7%) out of 30 ELISA positive specimens were also shown to be positive by either Western blot analysis (WB) or indirect immunogold electron microscopy (IIG EM). PMID- 2215232 TI - Studies on sandfly fauna (Diptera: Psychodidae) in a foci of cutaneous leishmaniasis in mesquita, Rio de Janeiro State, Brazil. AB - In a study on vectors of cutaneous leishmaniasis in Mesquita, Rio de Janeiro State, Brazil, eleven species of sandflies were found: Lutzomyia longipalpis, L. fischeri, L. quinquefer, L. intermedia, L. whitmani, L. shannoni, L. cortelezzii, L. edwardsi, L. migonei, L. lanei and L. firmatoi. Lutzomyia intermedia was the predominant species. It was collected indoors but in much higher numbers outdoors, in the close vicinity of houses. In comparative captures it was found to feed more frequently on equines, and less frequently on man and dogs. Studies, using man and animals as baits, showed that blood-feeding started in the evening, and remained stable during the night, until early morning. June, August and October were the months of highest density. PMID- 2215233 TI - Human leptospirosis in a slum area in the city of Rio de Janeiro, Brazil--a serological and epidemiological study. AB - A serologic survey was carried out on slum dwellers in the city of Rio de Janeiro. A total of 259 serum samples from male and female individuals of different age groups were tested for the presence of antileptospire antibodies by microagglutination. Prevalence data were analyzed in relation to the major risk factors present at the site, mainly represented by the presence of carrier animals and the occurrence of frequent floods. Of the samples tested, 25% reacted with antigens of different serogroups at titres ranging from 1:100 to 1:6400, with a predominance of titres less than or equal to 1:400; 35% of positive sera reacted with leptospirae of the Icterohaemorrhagiae serogroup. Reactions with Djasiman, Panama, Javanica, Canicola, Pyrogenes, Australis, Ballum, Sejroe, Bataviae, Grippotyphosa, Autumnalis and Cynopteri were also detected, though at lower frequencies. There was no statistically significant difference between sexes, but higher prevalence rates were found to be associated with increasing age. A focus of infection was characterized, in which social and economic factors contribute to the persistence of leptospirae by favoring the proliferation of the main reservoir. PMID- 2215234 TI - Distinct ultrastructural aspects in different biopsies of a single patient with diffuse cutaneous leishmaniasis. AB - The authors investigated the relation between parasites and host-cells in active and regressed lesions of a patient with diffuse cutaneous leishmaniasis, evaluating the frequency of different cell types, and the location and integrity of amastigotes. No correlation was found between parasite integrity and size of parasitophorous vacuoles. They observed ultrastructural findings characterizing a cell mediated immune response: macrophages lysis, parasitic destruction inside macrophages, close contact between parasitized macrophages and lymphocytes and between parasites and lymphocytes, lymphocytic infiltration and fibrosis. They suggest that in DCL there is a limited cellular immune response, although insufficient to control infection. PMID- 2215235 TI - Serotyping of Candida albicans isolated from clinical specimens. AB - A specific antiserum to Candida albicans serotype A was prepared absorbing a total antiserum with Candida albicans serotype B cells. This specific antiserum was used for serotyping C. albicans strains obtained from patients in different hospitals of Havana City, Cuba. Two hundred strains (95.2%) were serotype A, the remaining 10 (4.8%) were serotype B. Results were also correlated with strains isolated from the specimen origin, sex and race of the patient. The usefulness of this specific antiserum to determine C. albicans serotypes and its therapeutic value are pointed out. PMID- 2215236 TI - Technique for the detection of Toxoplasma gondii antigens in mouse urine. AB - A simple and rapid staphylococcal coagglutination test for the detection of Toxoplasma gondii antigens in mice urine is described. A suspension of protein-A containing Staphylococcus aureus coated with rabbit hyperimmune serum was used as reagent. The sensitivity of the antigen assay was found to be at least 118 ng of the antigen protein per ml. No coagglutination was observed when the reagent was challenged against antigenic solutions of other parasites. The suitability of the method for detecting antigens of T. gondii in urine samples was studied by experimental toxoplasma infection in mice. Before the staphylococcal test, the urine samples were double serially diluted in 0.1 M PBS. From the second day on all samples from infected mice were positive at 1/16 dilution. At this dilution, all samples from non infected mice were negative or did not produce coagglutination. This method might be used in the rapid etiological diagnosis also in human cases of acute toxoplasmosis. PMID- 2215237 TI - Human and dogs Toxocara canis infection in a poor neighborhood in Bogota. AB - Prevalence of Toxocara canis antibodies was studied in a poor community of Bogota, Colombia. Two-hundred-seven patients, from both sexes and all age groups, were studied. Positive ELISA titers were found in 47.5% of the population, a high prevalence compared with reports from developed countries. T. canis ova were positive in 43.6% of fecal samples from dog puppies. An endemic pattern of the disease is described: socioeconomic status, weather, pollution, poor hygiene and a significant population of infected dogs. Neither the physical examination nor ELISA titers could detect any case of T. canis disease. PMID- 2215239 TI - The Omnibus Budget Reconciliation Act-1987. An opportunity to institute a minimum data set for persons with developmental disabilities. PMID- 2215238 TI - Mechanism of action of a nitroimidazole-thiadiazole derivate upon Trypanosoma cruzi tissue culture amastigotes. AB - Megazol (CL 64,855) a very effective drug in experimental infections by Trypanosoma cruzi, and also in in vitro assays with vertebrate forms of the parasite, had its activity upon macromolecule biosynthesis tested using tissue culture-derived amastigote forms. Megazol presented a drastic inhibition of [3H] leucine incorporation, and only a partial inhibition of [3H]-thymidine and [3H] uridine incorporation, suggesting a selective activity upon protein synthesis. Comparing the three drugs, megazol was more potent than nifurtimox and benznidazole in inhibiting protein and DNA synthesis. Megazol showed a 91% of inhibition of [3H]-leucine incorporation whereas nifurtimox and benznidazole, 0% and 2%, respectively. These latter two drugs inhibited the incorporation of all the precursors tested at similar levels, but the concentration of benznidazole was always three times higher, suggesting different mechanisms of action or, more probably, a greater efficiency of the 5-nitrofuran derivate in relation to the 2 nitroimidazole. So, we conclude that the mode of action of megazol is different from the ones of nifurtimox and benznidazole and that its primary effect is associated with an impairment of protein synthesis. PMID- 2215240 TI - Historical and contemporary issues in nursing home reform. AB - Historical developments leading to the enactment of nursing home reform legislation (P.L. 100-203) were discussed. The results of the nursing home component of a nationwide University of Illinois at Chicago study of public mental retardation/developmental disabilities spending were also presented. Approximately 51,000 individuals with mental retardation and related conditions resided in nursing homes in 1989. The cost of their care was approximately $900 million annually. Within the first 12 months of the enactment of P.L. 100-203, 46 states had requested an extension to the original mandated services deadline imposed under that legislation. Under P.L. 100-203 guidelines, state agencies estimated that nearly 40% of all nursing home residents with mental retardation might need to be relocated to alternative settings. Implementation issues were also discussed. PMID- 2215241 TI - Mental retardation research in the Soviet Union. AB - Twenty-six studies on mental retardation conducted in the Soviet Union in the 1970s and 1980s were reviewed: 8 focused on etiological questions; 15, on psychoeducational issues; and 3, on vocational or social policy concerns. The findings, which tend to support general trends found in the United States for individuals with mental retardation, were: higher risk factors for mental retardation for children if the mother rather than the father had mental retardation; lower levels of education, lower occupational status, and a larger number of children for families of children with mental retardation (a significant finding in a society traditionally described as classless); and significantly higher number of males than females among persons with dual diagnoses. PMID- 2215243 TI - Effects of case manager feedback on the quality of individual habilitation plan objectives. AB - The functional relation between feedback by a case manager and improved writing of Individual Habilitation Plan (IHP) objectives in adult service agencies was assessed. Feedback on seven features of IHP objectives was delivered by the local case manager to program staff of four agencies providing residential or vocational support to adults with moderate to severe disabilities. The results demonstrate that each of the four agencies improved the quality of their written objectives after receiving feedback from the case manager and maintained those gains 18 months after feedback was terminated. Implications for case managers as feedback agents were discussed. PMID- 2215244 TI - Sheltered workshops: financial and philosophical liabilities. AB - Some of the economic and philosophical reasons why sheltered workshops remain liabilities within the field of special education were discussed. Low wage rates, the unavailability of work, changing industrial forecasts for blue collar employment, financial dependence, tax returns, segregation, and normalization issues, along with other factors, were examined to provide support for the assertion that sheltered workshops are not providing clients with appropriate work experiences. PMID- 2215242 TI - Follow-up study of family attitudes toward deinstitutionalization: three to seven years later. AB - The attitudes of 32 families who had their relative with mental retardation deinstitutionalized and living in the community for 3 to 7 years were examined. Preplacement data on these families indicated a high level of satisfaction with institutional services and strong opposition to community placement. Postplacement data revealed a significant change toward more positive family attitudes toward deinstitutionalization. However, families were still concerned about high staff turnover rates, inadequate community services, and future relocations. PMID- 2215245 TI - Residential placement of individuals with mental retardation: factors influencing court decisions. AB - Pennsylvania law mandates that involuntary commitment of persons with mental retardation be reviewed by the court system in order to assure due process. Fifty such cases in Philadelphia were reviewed in court over a period of one year and subsequently examined to determine current court trends toward institutional placement. Factors evaluated included characteristics of the individual, the presiding court, the impact of a court-appointed Child Advocate or Public Defender, and availability of residential alternatives. Results indicate that children were committed to institutional settings less frequently than adults. Other critical factors were prior placement, recommendations of advocates, and availability of alternative services. PMID- 2215246 TI - A reply to Professor Zeph. PMID- 2215247 TI - Thrombin stimulates the production of immunoreactive endothelin-1 in cultured human umbilical vein endothelial cells. AB - The present study was designed to examine the effect of thrombin on endothelin production by cultured human umbilical vein endothelial cells (HUVEC) by radioimmunoassay. Cultured HUVEC released immunoreactive endothelin-1 (ir endothelin-1) into the medium in a time-dependent manner. This release was inhibited completely by 10 micrograms/mL cycloheximide and is, therefore, directly related to de novo protein synthesis. Further endothelin release was stimulated by the addition of thrombin to the culture medium. Thrombin-induced ir endothelin-1 release also was inhibited completely by 10 micrograms/mL cycloheximide. These results suggest that HUVEC in culture produce ir-endothelin 1 slowly, but continuously, and that this production is stimulated by thrombin. PMID- 2215248 TI - Insulin resistance and acanthosis nigricans: evidence for a postbinding defect in vivo. AB - Acanthosis nigricans (AN) with insulin resistance has been traditionally attributed to insulin receptor abnormalities. To further clarify the postbinding defects of in vivo insulin action in this state, we applied the euglycemic insulin clamp technique, combined with the glucose trace infusion method, to 26 subjects: 12 AN patients (eight normoglycemic and four hyperglycemic), eight obese, and eight lean control subjects. The normoglycemic AN group exhibited fasting hyperinsulinemia (666% of control), 160% elevated hepatic glucose production (HGP), 425% increased posthepatic insulin delivery rate, and only slightly reduced (19%) insulin clearance rates, compared with controls. Except for the latter, all these abnormalities were statistically significant (P less than .05), and could not be accounted for by body overweight. AN patients with diabetes mellitus (AN + DM) exhibited a further decreased insulin responsiveness (30%) and clearance (38%), together with a major increase in HGP (320%). All AN patients showed a significant right-shift in the insulin dose-response curve, indicating a decrease in insulin sensitivity. In conclusion, AN is characterized by increased basal rates of HGP, and peripheral insulin resistance, which can be partially attributed to postbinding defects. In AN + DM, a worsening of these abnormalities may be responsible for unmasking the existence of diabetes. PMID- 2215249 TI - Urinary organic acid profiles in fatty Zucker rats: indications for impaired oxidation of butyrate and hexanoate. AB - The urinary excretion of 45 organic acids, monitored by gas-liquid chromatography, was compared in fatty (fa/fa) and lean (Fa/?) Zucker rats maintained on a chemically simplified diet. At the age of 6, 16, and 22 weeks, fatty rats excreted more of the various organic acids than their lean counterparts. However, the greatest difference was in the excretion of ethylmalonate, even when excretion data were normalized to body weight. The next highest excretion difference was in adipate and an unknown compound, and the third highest in pyruvate. A second group of rats examined at 7 weeks also excreted an excess of these four acids, as well as glucuronate and indole-3 acetate. The excessive excretion of ethylmalonate and adipate, which is characteristic of human genetic defects in short- and medium-chain fatty acid oxidation, suggested that the oxidation of butyrate and hexanoate might be impaired in the fatty rat. Thus, as a test of their capacity to oxidize medium- and short-chain fatty acids, two groups of fatty and lean rats were transferred to diets enriched with either trioctanoylglyceride, a medium-chain triglyceride (MCT), or sodium butyrate, a short-chain fatty acid. Both lean and fatty rats on the MCT diet, but only the lean rats on the butyrate-enriched diet, increased their excretion of adipate. However, on both the MCT and butyrate diet, ethylmalonate excretion increased only in lean rats, almost reaching amounts found previously in fatty rats. These results suggest that the fatty rat has an impairment of the beta-oxidation of butyrate and hexanoate, a defect that might increase intracellular concentrations of butyryl-CoA, the optimal primer for the synthesis of long-chain fatty acids. PMID- 2215250 TI - Metabolism of adipose tissue in intraabdominal depots in severely obese men and women. AB - In groups of obese men and women with an abdominal type of fat distribution, we measured fat cell size, lipoprotein lipase (LPL) activity and lipolysis stimulated by norepinephrine (NE) or isoproterenol (ISO) or inhibited by insulin, in subcutaneous abdominal and retroperitoneal (nonportal), as well as in omental and mesenteric (portal) adipose tissues. Both men and women had large intraabdominal adipocytes. No differences were found between the two groups of obese subjects in fat cell size or LPL activity in the different adipose tissue regions. Women had as high NE- or ISO-stimulated lipolysis in the portal as in nonportal fat tissues, equally high as that found in men. In comparisons with a previous study in nonobese men and women, these results show an increased fat cell size in all tissues in obese women and an increased lipolysis in portal tissues in obese women and in nonportal tissues in obese men. Taken together, these results might mean that obese men and abdominally obese women have a large potential to release free fatty acids (FFA) from intraabdominal depots. This might be followed by metabolic derangements seen in such groups of obese subjects. PMID- 2215251 TI - Metabolism of ketone bodies by skeletal muscle in starvation and uncontrolled diabetes. AB - Previous studies have suggested that skeletal muscle may be responsible for as much as 25% of ketone body (KB) production in poorly controlled diabetes. In the present studies, acetoacetate (AcAc) and beta-hydroxybutyrate production was quantitated in the canine hindlimb from surgically placed arterial and venous catheters in conscious insulin-withdrawn diabetic (n = 5) and 4-day fasted (n = 7) dogs. A two-pool modeling technique, using simultaneous infusions of 13C acetoacetate and 14C beta-hydroxybutyrate (beta OHB) was employed to quantitate total body and hindlimb KB kinetics. Total KB production was 9.4 and 39.3 mumol.kg-1.min-1 in the fasted and diabetic animals, respectively. Hindlimb KB production was negligible in both groups. The two-pool model estimates of hindlimb KB utilization were similar to the values obtained by an arterial-venous difference calculation. In conclusion, the hindlimb does not contribute to de novo synthesis of KBs in either fasted or diabetic dogs. Since species differences in KB metabolism occur, it is possible that muscle may be a site for KB production in humans. PMID- 2215252 TI - Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1. AB - Recent epidemiologic studies have shown that abdominal obesity, characterized by a high waist to hip circumference ratio (WHR), is associated with increased cardiovascular morbidity and mortality. The present study examines components of the fibrinolytic system in obese and lean middle-aged women with a high and low WHR. Ten women in each group were carefully matched with respect to age, body weight, lean body mass, and body fat. Fibrinogen and endothelial type of plasminogen activator inhibitor -1 (PAI-1) were significantly elevated in the obese women with a high WHR compared with the obese women with a low WHR or with both groups of lean women. In addition, obese women with a high WHR exhibited a greater metabolic risk profile (elevated glucose, insulin, and triglyceride levels). When all subjects were pooled for the analyses, both fibrinogen and PAI 1 levels correlated positively with glucose and insulin levels. PAI-1 was also negatively related to degree of insulin sensitivity measured with the euglycemic clamp technique. In the obese groups, WHR but not body mass index (BMI), correlated with PAI-1 levels. No such correlations were seen in the lean groups. In conclusion, the data show that a high WHR in obese, but not lean middle-aged women, is associated with an impaired fibrinolytic activity. This perturbation becomes enhanced when it is associated with hyperinsulinemia and insulin resistance, which is a typical feature of abdominal obesity. PMID- 2215253 TI - Impaired glucose tolerance and diabetes in obesity: a 6-year follow-up study of glucose metabolism. AB - To investigate the time course of glucose metabolism in obesity 33 patients (21 to 69 years old; body mass index [BMI], 25.7 to 53.3 kg/m2) with different degrees of glucose intolerance or diabetes who had been studied initially and 6 years later were submitted to the same 100-g oral glucose tolerance test (OGTT) with indirect calorimetry. From a group of 13 obese subjects with normal glucose tolerance (NGT), four developed impaired glucose tolerance (IGT); from a group of nine patients with IGT, three developed non-insulin-dependent diabetes mellitus (NIDDM); five of six obese NIDDM subjects with high insulin response developed NIDDM with low insulin response. Five patients had diabetes with hypoinsulinemia initially. As previously seen in a cross-sectional study, the 3-hour glucose storage measured by continuous indirect calorimetry remained unaltered in patients with IGT, whereas it decreased in NIDDM patients. A further decrease in glucose storage was observed with the lowering of the insulin response in the previously hyperinsulinemic diabetics. These results confirm cross-sectional studies that suggest successive phases in the evolution of obesity to diabetes: A, NGT; B, IGT (the hyperglycemia normalizing the glucose storage over 3 hours); C, diabetes with increased insulin response, where hyperglycemia does not correct the resistance to glucose storage anymore; and D, diabetes with low insulin response, with a low glucose storage and an elevated fasting and postload glycemia. PMID- 2215254 TI - Repeated ingestion of aspartame-sweetened beverages: further observations in individuals heterozygous for phenylketonuria. AB - Six adults heterozygous for phenylketonuria (PKU) ingested eight successive servings of unsweetened and aspartame (APM)-sweetened beverage at 1-hour intervals in a randomized, balanced, crossover design. In one part, the eight beverage servings were not sweetened. In the other, each of the eight beverage servings provided 600 mg of APM, a dose equivalent to the amount provided by 36 oz of an APM-sweetened diet beverage. Plasma aspartate concentration was not significantly increased after ingestion of unsweetened or APM-sweetened beverage. Similarly, ingestion of the unsweetened beverage had no significant effect on plasma phenylalanine concentration. However, ingestion of APM-sweetened beverage significantly increased plasma phenylalanine concentrations 2.35 to 4.03 mumol/dL above baseline 30 minutes after ingestion. Plasma phenylalanine values reached a steady-state after administration of five servings of APM-sweetened beverage and were slightly, but significantly higher than usual postprandial values for adults heterozygous for PKU. Similarly, the ratio of the plasma phenylalanine concentration to the sum of the concentration of the large neutral amino acids was significantly higher than usual postprandial values. Blood methanol and formate concentrations remained within normal limits. These data indicate that a fasting adult heterozygous for PKU could consume the equivalent of 24 12-oz servings of APM-sweetened beverage over an 8-hour period and only increase plasma phenylalanine concentration to a modest degree. PMID- 2215255 TI - Dual effect of metformin in cultured rat hepatocytes: potentiation of insulin action and prevention of insulin-induced resistance. AB - The ability of the biguanide hypoglycemic agent metformin to improve the acute effects of insulin on glucose and/or lipid metabolism was investigated in both insulin-responsive and insulin-resistant cultured rat hepatocytes: (1) metformin (20 micrograms/mL, 16 hours) increased the insulin-dependent stimulation of glycogen and lipid synthesis through an exclusive enhancement of the responsiveness without modification of the cell sensitivity to the hormone; (2) metformin neither altered basal glycogenesis from [U-14C]glucose and basal lipogenesis from [1-14C]acetate nor insulin binding. These results indicate the ability of this drug to selectively potentiate the acute action of insulin at a postreceptor step in normal liver cells. A prolonged incubation with insulin (16 hours, 5 x 10(-7) mol/L) led the hepatocytes to a state of resistance evidenced by a 50% decrease in their maximal responsiveness and sensitivity to a subsequent acute stimulation by the hormone, as assessed on lipogenesis. Addition of metformin (20 micrograms/mL) during the overnight incubation of hepatocytes with insulin prevented the decrease in cell responsiveness and sensitivity to the hormone for the stimulation of lipogenesis, thus showing that metformin was able to hamper the development of the resistant state to the hormone in this pathway. These results strongly suggest that metformin improves type 2 diabetes through an effect at the hepatic level on both insulin action and insulin-induced resistance. PMID- 2215256 TI - Insulin-mediated glucose uptake by individual tissues during sepsis. AB - Gram-negative hypermetabolic sepsis has been previously reported to produce whole body insulin resistance. The present study was performed to determine in vivo which tissues are responsible for the sepsis-induced decrease in insulin-mediated glucose uptake (IMGU), and whether that decrease was related to a change in regional blood flow. Vascular catheters were placed in rats and sepsis was induced by subcutaneous injections of Escherichia coli. Insulin action was assessed 20 hours after the first injection of bacteria by the combined use of the euglycemic hyperinsulinemic clamp and the tracer 2-deoxyglucose (dGlc) technique. Insulin was infused at various rates in separate groups of septic and nonseptic rats for 3 hours to produce steady-state insulin levels between 70 and 20,000 microU/mL. Rats were injected with [U-14C]-dGlc 140 minutes after the start of the euglycemic hyperinsulinemic clamp for the determination of the glucose metabolic rate (Rg) in selected tissues. The maximal response to insulin was decreased 30% to 40% in the gastrocnemius, and in the red and white quadriceps. The former two muscles also showed a decrease in insulin sensitivity. However, the insulin resistance seen in hindlimb muscles was not evident in all muscles of the body, since IMGU by abdominal muscle, diaphragm, and heart was not impaired by sepsis. The basal Rg by skin, spleen, ileum, and lung was increased by sepsis, and was higher than the insulin-stimulated increases in Rg by these tissues in nonseptic animals. Cardiac output was similar in septic and nonseptic rats and did not change during the infusion of insulin. Under basal conditions, sepsis appeared to redistribute blood flow away from the red quadriceps and skin, and increased flow to the liver (arterial), lung, and small intestine. When plasma insulin levels were elevated, hepatic arterial blood flow was increased, and flow to the red quadriceps and skin was decreased in nonseptic animals. Hyperinsulinemia did not produce any consistent change in regional blood flow in septic animals. The results of this study indicate that a decrease rate of IMGU in muscle is primarily responsible for the whole body insulin resistance seen during hypermetabolic sepsis, and that the impairment of insulin action in skeletal muscle is not dependent on fiber type or to changes in blood flow. PMID- 2215257 TI - Hospital information systems and the quality of therapeutics. PMID- 2215258 TI - Using connectionist modules for decision support. AB - A connectionist model for decision support was constructed out of several back propagation modules. Manifestations serve as input to the model; they may be real valued, and the confidence in their measurement may be specified. The model produces as its output the posterior probability of disease. The model was trained on 1,000 cases taken from a simulated underlying population with three conditionally independent manifestations. The first manifestation had a linear relationship between value and posterior probability of disease, the second had a stepped relationship, and the third was normally distributed. An independent test set of 30,000 cases showed that the model was better able to estimate the posterior probability of disease (the standard deviation of residuals was 0.046, with a 95% confidence interval of 0.046-0.047) than a model constructed using logistic regression (with a standard deviation of residuals of 0.062, with a 95% confidence interval of 0.062-0.063). The model fitted the normal and stepped manifestations better than the linear one. It accommodated intermediate levels of confidence well. PMID- 2215259 TI - A method for the acquisition of formalized knowledge in pathology. AB - A tool is introduced for the acquisition of pathology knowledge in a formalized form, directly by the expert. Formalization of the knowledge is intended to make descriptive pathology knowledge more suitable for computerized diagnostic support since a formal representation of knowledge allows more extensive indexing, hence more flexible access. The knowledge acquisition (KA) tool also provides a useful research instrument to investigate to what extent pathology knowledge can be made explicit, to what degree ambiguity is present, in what way experts differ when formalizing knowledge, and whether it is feasible to incrementally acquire decision criteria on the basis of the formalized descriptive knowledge. Crucial in the design of the KA tool is the incorporated meta-knowledge, which is reflected by the knowledge-base structure and is used to elicit knowledge from the expert. Knowledge is acquired from the expert via a menu-driven user interface, which follows the general steps of the pathologist when describing a case. The paper discusses the considerations underlying the design, the implementation of the KA tool, and the research goals. PMID- 2215260 TI - BRAINDEX: an interactive, knowledge-based system supporting brain death diagnosis. AB - BRAINDEX (Brain-Death Expert System) is an interactive, knowledge-based expert system offering support to physicians in decision making concerning brain death. The physician is given the possibility of communicating in almost natural language and, therefore, in terms with which he is familiar. This updated version of the system is implemented on an IBM-PC/AT with the expert system shell PC-PLUS and consists of about 430 rules. The determination of brain death is realized with backward chaining and for the optional coma-scaling a forward-chaining mechanism is used. PMID- 2215261 TI - Cluster analysis of antigenic profiles of tumors: selection of number of clusters using Akaike's information criterion. AB - A basic problem of cluster analysis is the determination or selection of the number of clusters evinced in any set of data. We address this issue with multinomial data using Akaike's information criterion and demonstrate its utility in identifying an appropriate number of clusters of tumor types with similar profiles of cell surface antigens. PMID- 2215262 TI - Use of a hospital database to determine the characteristics of diagnostic tests. AB - Test indices are often determined by comparing test results of healthy persons with test results of patients known to have the disease. However, the patient population for which the test is ordered in clinical practice often differs from the study population on which the test indices are based. Hence, these indices are not applicable to clinical practice and should be recalculated using data from daily clinical practice. Two major problems of using routinely collected data are discussed: the assessment of the final health status and tracing the reason for ordering the test. Prior considerations are given to the use of hospital information systems (HIS) to sample the patient population that is desired and to collect the necessary data for calculating test indices. We investigated whether the HIS of Leiden University Hospital (which is presented as an example) can be used to calculate the indices of clinical laboratory tests, histopathologic examinations and radiodiagnostic investigations. The results indicate that the registration of diagnoses must be improved and that a way must be found to capture the implicit reasoning for ordering diagnostic tests. PMID- 2215263 TI - Sensitivity and specificity of acid phosphatase to detect prostate cancer using data from a hospital information system. AB - Indices of diagnostic tests, such as sensitivity and specificity, should be determined using diagnostic test results of patients tested in clinical practice. Hospital information systems that store data on diagnostic tests and diagnoses might be used for sampling the desired study population and in the actual process of collecting the data. This paper presents, as an example, a study calculating the sensitivity and specificity of the prostate-specific acid phosphatase test. All data needed in the study were obtained from the hospital information system of Leiden University Hospital. The final health status of each patient was assessed by the cancer registry of the system. The reason for ordering the test was deduced from data on histopathological examinations of prostatic tissue. The actual selections made from the central database are described in dataflow diagrams. The sensitivity of the test was found to be 0.34 and the specificity 0.88, using a discrimination value of 1.00 U/l. The impact of the reason for ordering the test on the specificity is illustrated. Possible biases of these measured values are discussed. PMID- 2215264 TI - Converting the representation of medical data: criteria to code the underlying cause of death. AB - This study deals with a set of coding directives that were conceived for trained coding clerks and rely upon knowledge of their cultural background. These directives were formalized and adapted for computer use and in this form must rely upon a background of explicit medical knowledge. Medical data on death certificates are an invaluable source of information regarding prevention of major causes of death. These causes are coded and tabulated worldwide by means of the International Classification of Diseases (ICD). The ICD manual issues directives to achieve uniformity of coding throughout the world. The coder is required to trace back the flow of events which caused death and to single out the most significant concept from the statistical point of view. After emphasizing the problems encountered in the formalization, the methodological contribution of this work to the identification of a modular architecture for a system which represents and "reshapes" knowledge from medical documents is presented. Therefore we focus on the features of the two kinds of knowledge that must be supplied to a knowledge-based system, in order to enable it to perform semantic conversions on given medical data, namely: i) generic guidelines; ii) detailed medical knowledge. PMID- 2215265 TI - Detection of aberrant observations in a background of an unknown multidimensional Gaussian distribution. AB - An exploratory iterative technique for the detection of aberrant observations on a background of a multidimensional Gaussian distribution is described. Its development was motivated by the analysis of a set of three measurements reflecting the acid-base metabolism in the blood of 2,402 intensive care patients. This new, three-dimensional treatment of such data yields a meaningful description. A technical evaluation of the method, using artificially generated data is also presented. It is shown that the model parameters of the underlying Gaussian distributions are determined with good accuracy and that the accuracy with which the contamination is estimated increases with increasing distance of the contaminating observations from the mean. PMID- 2215266 TI - Planning the size of clinical trials with allowance for patient noncompliance. AB - Various approaches are considered for adjustment of clinical trial size for patient noncompliance. Such approaches either model the effect of noncompliance through comparison of two survival distributions or two simple proportions. Models that allow for variation of noncompliance and event rates between time intervals are also considered. The approach that models the noncompliance adjustment on the basis of survival functions is conservative and hence requires larger sample size. The model to be selected for noncompliance adjustment depends upon available estimates of noncompliance and event rate patterns. PMID- 2215267 TI - 25 years of hormonal replacement therapy. PMID- 2215268 TI - The history and rationale of hormone replacement therapy. AB - Robert Wilson rendered women aged over 45 a great service. He provoked a line of research which has in 25 years resulted in a sensible approach towards the use of medication in treating the climacteric and post-menopausal oestrogen deficiency. The history of hormone replacement therapy (HRT) is described, as is the current approach to rational HRT. Some ideas are outlined for future development. PMID- 2215269 TI - Clinical use of oestrogens and progestogens. AB - Oestrogens cure climacteric complaints and prevent the late sequelae of oestrogen deficiency. Prevention of myocardial infarction and of osteoporosis is now the main argument for long-term substitution of oestrogens and progestogens in the post-menopause and leads to a reduction of overall morbidity and mortality in users. Indications, contraindications, some side effects, risk-benefit and cost benefit considerations are discussed and practical advice for oestrogen medication with regard to doses, preparations and the addition of progestogens is given. PMID- 2215270 TI - Hormonal replacement therapy and the skeletal system. AB - The two most important risk factors for maintaining skeletal health are the bone mass obtained at skeletal maturity (peak bone mass) and the subsequent bone loss. Those women with a low peak bone mass and a rapid bone loss are thus at increased risk of developing osteoporosis in the future, and should be identified. This may be accomplished by determination of the bone mass combined with an estimate of the rate of the postmenopausal bone loss. The bone mass can be accurately assessed in the forearm by single photon absorptiometry. The postmenopausal bone loss can be estimated by three or four biochemical markers of bone turnover. The women at highest risk of developing osteoporosis should be offered preventive therapy, e.g., hormonal replacement therapy (HRT). HRT arrests the bone loss not only in early, but also in elderly postmenopausal women. The effect lasts as long as the therapy is continued. Several epidemiological studies have demonstrated that HRT decreases the number of osteoporotic fractures. PMID- 2215271 TI - Ovarian hormones and the circulation. AB - Ovarian steroids have effects on blood circulation involving the mechanisms which control blood flow and the changes that occur in the pathogenesis of atherosclerosis. Estrogens appear to protect women from cardiovascular disease through their effects on lipid metabolism as well as more direct effects on arterial walls which appear to inhibit atherosclerotic plaque formation. There is increasing evidence that estrogen replacement after menopause can markedly reduce female mortality due to vascular disease. Effects of hormone imbalance and deficiency on vasomotor control are clinically significant and hormone treatment appears to be effective in the management of a variety of conditions due to abnormal blood flow including vasomotor instability, migraine, vaginal dryness and, perhaps, some forms of angina. Most review articles have focused on the effects of ovarian steroids and lipid metabolism as well as the findings of recent epidemiologic studies. This is understandable as those investigations have proved so valuable in understanding the protective effects of estrogens. The present discussion, in contrast, focuses on the effects of ovarian steroids, estrogens in particular, on circulatory mechanisms. At the present time there is increasing interest in these studies. Findings thus far appear to contribute to understanding estrogen cardioprotection and also raise awareness of a variety of clinical conditions in which estrogen treatment could be indicated because of its effects on circulation. PMID- 2215272 TI - Emotional well-being, sexual behaviour and hormone replacement therapy. AB - Improvements in the design of epidemiological studies of the climacteric and postmenopause have been made in the past 25 years. But more complex theoretical models are necessary if we are to give due emphasis to the influence of psychological, social, cultural and hormonal factors and their interactions. The majority of studies show that emotional problems are not more prevalent during the climacteric and postmenopause and that psychosocial factors, such as stressful life-events, are more likely causes of emotional distress during mid life. Vaginal dryness increases in postmenopausal women but there are varied reasons for changes in other aspects of sexual behaviour which require further research. While estrogen may have a "mental tonic" effect when prescribed in high doses, HRT does not appear to have a significant effect upon mood or sexual behaviour over and above placebo effects and the relief from vasomotor and vaginal symptoms. PMID- 2215273 TI - The value of the menopause clinic, a personal opinion. PMID- 2215274 TI - Policyholder seeks fair payment from the Blues. PMID- 2215275 TI - Physician office reimbursement problems. Help is at hand. PMID- 2215276 TI - Michigan physicians to face growing numbers of HIV-positive patients. PMID- 2215278 TI - MSMS Medicaid Liaison Committee--an independent voice for physicians. PMID- 2215277 TI - Kevin Seitz--working to build a healthier Medicaid system. PMID- 2215279 TI - Michigan Orthopedic Society. Delivery of care has become a serious issue. PMID- 2215280 TI - When it comes to health insurance, MSMS members have many lessons to learn. PMID- 2215281 TI - Government must address increase in repetitive motion injuries. PMID- 2215282 TI - Informed consent: an update. PMID- 2215283 TI - [The composition of a population of cloned cultures of revertant Vibrio cholerae L forms]. AB - The process of L-transformation and L-transformed state duration have been studied for their effect on variability of main characters of revertant cultures of choleric vibrions L-forms at the population level with the use of cloned cultures of the choleric vibrions. The study was conducted on two strains of the choleric vibrion of the eltor biovar in different periods of storage in the L transformed state (1, 3, 6 months). It has been revealed that characters of the species and biovar remained stable despite the influence of L-transforming agents. The characters of clone cultures characterizing virulence (sensitivity to KhDF phages, hemolytic activity, toxin production and virulence for sucking rabbits proved to be subjected to variability to the greatest extent with simultaneous preservation of the toxin-production gene. A resistant change of the serovar (from Inaba to Ogava) is observed only in one revertant-subculture of the virulent strain. PMID- 2215284 TI - [A comparative study of the oxidation processes in the cells of typical forms and L forms of Vibrio cholerae]. AB - A comparative study of metabolic processes in cells of typical forms and L-forms of cholera vibrios has determined a change in the intensity of oxidative processes demonstrated through a decrease in the activity of respiration enzymes (dehydrogenases and diaphorases) and through a restricted transport of electrons along the respiration chain. The facts established evidence for the transition of L-transformed cells into a physiological state with a deficit of substrates and energy as well as with retarded processes of vital activity and repressed mechanisms of reparation of structural elements of a cell. PMID- 2215285 TI - [The characteristics of the biosynthesis of surface-active lipids by a Bacillus sp. culture]. AB - It is established that the Bacillus sp. C-14 strain is able to produce the biosurfactant of lipopeptide nature which decreases the surface and interfacial tension to 29.5 and 2.0 mH/m, respectively. The biosurfactant synthesis is shown to depend on the substrate nature, N:C ratio in the medium as well as on the presence of sodium citrate as a stimulator of lipogenesis. PMID- 2215286 TI - [An immunological analysis of the hemagglutinin from the influenza A virus (H1N1) isolated by using various detergents]. AB - Immunogenic properties of influenza virus hemagglutinin, isolated by new detergents O-14 (desintegron-O) and B-14 (desintegron-B) have been studied. Hemagglutinin isolated by desintegron-O has been found to be more immunogenic than virions. It has been shown that hemagglutinin isolated by desintegron-B induces a lower humoral immune response than the influenza virus. PMID- 2215287 TI - [The possibilities for enhancing the immunogenicity of adenovirus hexon]. AB - Synthetic polyelectrolytes and muramyldipeptide derivatives are tested as immunostimulators. It is established that the level of antibody-forming cells and specific (virus-neutralizing and precipitating) antibodies considerably rises during the immunization of human adenovirus I hexon in the combination with N acetylglucosaminyl-muramyldipeptide and conjugation with a copolymer including acrylic acid and N-vinylpyrrolidone. A more expressed intensification of the antibody-formation is observed with the use of polyelectrolytes. PMID- 2215288 TI - [The mitogenic properties of Fusarium graminearum and Rhodococcus erythropolis enzymes]. AB - Blast transformation of peripheral blood lymphocytes in healthy people is studied by enzymes of the microbic origin possessing the lectin activity. Galactose oxidase of Fusarium graminearum IMV-F-1060 is shown to be mitogenically active with respect to the lymphocytes in the culture in vitro and may be one of home sources of lymphocytic mitogens for the laboratory investigations. PMID- 2215289 TI - [The virulence and antibiotic resistance of Escherichia isolated from man]. AB - The virulence and antibiotic resistance of the same 75 strains of pathogenic Escherichia (PE) has been studied. Simultaneous determination of virulence in three tests (keratoconjuctival, intranasal and with the infection of cell culture) has permitted increasing detection of virulence strains to 97.4%. Differences of PE in O-antigen as well as differences of strains depending on the source of their isolation (a sick or a healthy carrier) have not an essential effect on the PE virulence. Drug resistance of PE was induced by neomycin (the highest degree) and by other antibiotics (arranged in the descending order): mycin, streptomycin, laevomycetin, polymyxin, tetracyclin and gentamycin. PMID- 2215290 TI - [The adhesion of lactic acid bacteria to the intestinal epithelium of agricultural animals]. AB - The lactic acid bacteria isolated from different ecological niches are established to be able to adhere in vitro to the intestine epithelium of pigs and cattle. The studied strains of enterococci have a higher index of adhesiveness (5.7-2.24) as compared to lactic acid bacilli (3.34-1.08). Detection of the lactic acid bacteria ability to adhere to intestine enterocytes of agricultural animals served as a premise to use those bacteria when constructing preparations of the directed action on the basis of living cultures. PMID- 2215291 TI - [Proteus adhesion to intestinal epithelium]. AB - The adhesive properties of Proteus strains isolated from different sources have been studied under conditions similar to the real interaction of microorganisms with the epithelial cells of intestine. A comparison of the adhesive properties of Proteus and of colon Bacillus has shown that the value of the strong adhesion to the mucosa of Proteus isolated under enterocolitis at the same bulk concentrations of the infectious suspension is 2-3 order less than that of E. coli. The adhesion of Proteus to the surface of epithelial cells begins at bulk concentrations exceeding those for the colon Bacillus by 3-4 orders. Besides, a toxic effect of number of freshly isolated Proteus strains on the epithelial cells of intestine mucosa is observed. Strains isolated from patients with diarrhea and from environment differed from each other in the studied criteria. A conclusion is drawn that at the initial stage of the interaction with the intestine mucosa the Proteus strains differ considerably from the indigenous strain of the colon Bacillus in the ability to colonize the epithelial surface. PMID- 2215292 TI - [The extracellular lectins of bacteria]. PMID- 2215293 TI - Development of continuing medical education in Europe: a review. AB - This short review sets out some general facts and features concerning the development of continuing medical education (CME) in Europe. The review is intended as a basis for proposing plans and action for CME in the future. Europe, as it happens, was the birthplace and cradle of both scientifically based medical education in general and CME in particular. Three stages of development are distinguished: (1) Development of CME from the 19th century up to the beginning of the Second World War; (2) After 1945; (3) CME in the present. PMID- 2215294 TI - Quantitative assessment of diagnostic ability. AB - This paper describes variables critical to diagnostic thinking that are based on research by Bordage and Grant & Marsden on the diagnostic thinking of medical students and experienced doctors. The purpose of the study is to use their findings to develop an inventory of diagnostic thinking. A 56-item diagnostic thinking inventory was initially developed; each item contains a stem followed by a 6-point, semantic differential scale. The inventory is designed to measure two aspects of diagnostic thinking: the degree of flexibility in thinking and the degree of knowledge structure in memory. The specific goal of the study is to determine which items discriminate best between weaker and stronger diagnosticians and to reduce the inventory to only those items which significantly contribute to the overall score. Thirty subjects from nine groups, each representing a distinct phase of medical education and clinical practice, participated, namely first- and third-year clinical medical students, house officers, senior house officers, registrars, senior registrars, consultants, trainees in general practice, and general practitioners, all from the UK (n = 270). Discrimination indices were calculated for each item. The revised version of the inventory contains 41 items. All the subjects found the exercise meaningful and the resulting scores showed variance and discrimination. The inventory will eventually be used to assess individual student's and clinician's diagnostic thinking and to plan ways of improving their diagnostic thinking. PMID- 2215295 TI - Self-directed learning in anatomy: incorporation of case-based studies into a conventional medical curriculum. AB - This paper reports an attempt to develop self-directed learning skills in second year medical students by introducing case-based projects into the gross anatomy course at a long-established medical school. The programme and students' responses to a questionnaire completed at the end of the year are presented. Information on the various resources used by students to find information is given. The performance of students in the case-based components of the course has been evaluated and also in the more traditional end-of-year written examination. The data confirm that students have recognized that the projects were about obtaining a deeper understanding of the anatomy, and the programme appears to have promoted the use and study of library texts. PMID- 2215296 TI - Communication skills and clinical methods: a new introductory course. AB - In the revised medical curriculum at Sheffield University, a new 4-week introductory clinical course has been introduced to teach communication skills, clinical history-taking and physical examination. There is no formal examination for the course, which has been evaluated by feedback from students and tutors with questionnaires and group discussion. PMID- 2215297 TI - Early diagnosis of substance abuse: evaluation of a course of computer-assisted instruction. AB - A computer-assisted, experiential course of instruction on early diagnosis of substance abuse was developed and compared to three existing substance abuse curricula for third-year medical students on family medicine clerkships. The experimental course, requiring 2 hours of teacher contact, consisted of three computer-assisted instruction modules, active discussion, role play, opportunities for applying new knowledge and clinical skills, and modelling of clinical interest by a family doctor. The three comparison educational programmes were a one-week immersion experience on a substance abuse in-patient unit, 1-4 hours of lecture, and no formal teaching. For 6 months, all third-year medical students at Jefferson Medical College were exposed to one of these courses, and to the same required readings on substance abuse, on their required family medicine rotations at different clerkship sites. They completed end-of-rotation questionnaires assessing their knowledge, satisfaction with substance abuse teaching, and motivation for continued learning. Groups were similar with regard to demographic variables, academic performance, and previous curricular and extra curricular exposure to substance abuse. Despite a possible selection bias favouring the immersion experience, the computer-assisted course resulted in higher levels of knowledge on early diagnosis, but similar attitudes and satisfaction. The computer-assisted and immersion courses produced more favourable outcomes than lecture-based teaching and no formal teaching. Compared to no formal teaching, lecture did not produce measurable effect. The results suggest that a computer-assisted, experiential substance abuse course, based on relevant and practical goals, can efficiently augment knowledge and motivation for further learning of third-year medical students. PMID- 2215298 TI - Televised paediatric consultations: a student evaluation of a multipurpose learning strategy. AB - Since 1984, each student in the sixth-year paediatric rotation in the Department of Paediatrics and Child Health at the University of the Witwatersrand has been videotaped while undertaking a comprehensive paediatric primary care consultation. Video replay of the consultation by each individual student was evaluated by the student together with medical and social work tutors. This incorporated psychosocial aspects, communication skills, doctor-mother-child interactions, as well as essential medical content, clinical examination techniques, and management strategies. The student was expected to provide comprehensive health care, viz. dealing with the presenting health problems, identifying any possible hidden agenda, giving due attention to nutrition, immunization, development, optimal use of available records, health surveillance and appropriate education. This teaching programme was introduced in 1984. In 1988, 68 consecutive final-year medical students completed an anonymous Likert type evaluation form scoring their perceived learning. They affirmed that the use of television in medical education provides a unique multipurpose learning strategy and in particular enhances awareness of self and of patient/family needs. The time, cost and effort invested in this programme are considered justified. PMID- 2215299 TI - Changes in attitudes towards psychiatry among medical students: correlation of attitude shift with academic performance. AB - This study investigates the changes in attitudes to psychiatry and level of psychiatric knowledge among medical students before and after formal teaching on psychiatry. Teaching led to the development of more favourable attitudes (particularly among women) towards psychiatry, but doubt remained after teaching about the 'scientific' status of the discipline. Initial attitudes did not relate to academic performance but, those developed after teaching showed a significant positive correlation with it. PMID- 2215300 TI - Evaluating family counselling skills training for family practice. AB - Educational programmes for family practice should develop family counselling skills of students to moderate levels of competence. Few specific training programmes are part of the regular curriculum and of these few are evaluated. Twenty-three residents enrolled in a 2-year family practice programme in Toronto, Canada participated in a non-randomized control intervention study to assess a specific training programme. Pre-training counselling skills, and ability were assessed using two types of generally recognized measurement instruments, the Carkhuff Stems of Communication Skills and the Carkhuff Discrimination Index. The treatment group entered the training programme which involved supervised family counselling 8 half-days each week for one month as part of their usual rotations. They completed a second set of instruments following this course to assess immediate within-group change and then both they and the control group completed a set about one year later to measure differences. Initial scores for all residents showed a less than 'minimally facilitative' level of counselling response on both empathy and warmth dimensions. Following the course, the treatment group scored above this level and significantly better than the control group. Furthermore, the former showed a 20% improvement in ability to discriminate between effective and ineffective helping responses which was sustained over one year, while the control group's scores became worse. Teaching of counselling skills can be effective. PMID- 2215301 TI - Medical education for the prevention of torture. AB - The United Nations Convention against Torture came into force on June 1987 and the European Convention for the Prevention of Torture on 1 February 1989. The two Conventions are complementary and do not overlap in any respect, including their relevance to training of health personnel. The United Nations Convention calls for education of all doctors and other health personnel. Education should therefore be at the undergraduate level and should provide an insight into torture methods, the goal and objectives of torture and the sequelae of torture so that doctors can identify victims of torture. Refugee victims of torture should not be sent back to countries where they are at risk of torture. The main principles of treatment must also be taught. The European Convention makes no demands for education of doctors in general and thereby no demands for undergraduate training. However, the activities of the Committee necessitate special postgraduate training of a limited number of persons: members of the committee, experts and interpreters. PMID- 2215302 TI - Tropical doctors and statistics. PMID- 2215303 TI - Human embryo experimentation and surrogacy. PMID- 2215304 TI - Fetal ultrasound for entertainment? PMID- 2215305 TI - Swallowing disorders in stroke. PMID- 2215306 TI - The incidence and distribution of RSI in South Australia 1980-81 to 1986-87. AB - Despite the human and financial cost of repetition strain injury (RSI), comprehensive incidence data have been lacking. A unique opportunity exists to obtain such data in South Australia, where since 1980-81 the Australian Bureau of Statistics has assigned all injuries, not explicitly diagnosed as diseases but stated as having been caused by repetitive movement, to a unique "type of accident" code, and has subclassified them according to bodily location. The statistical profile of diseases and accidents affecting the upper limb resulting from repetitive movement is not simply one of a keyboard operators' epidemic. Rather, it has revealed a problem which is endemic in sections of the blue-collar workforce, in whom both the numbers and the incidence rates are higher than in keyboard operators, and were higher even when the incidence in keyboard operators peaked in 1984-85. These conditions have been especially frequent in particular sections of the female blue-collar workforce, and interventions which have resulted in (or coincided with) benefits to keyboard operators have failed to improve the situation in the former group. It is suggested that the groups most at risk are female workers performing unfulfilling, unskilled tasks, and that interventions to benefit these workers will have to give attention to more fundamental issues than those hitherto addressed. PMID- 2215307 TI - Prevalence of maternal HIV infection based on anonymous testing of neonates, Sydney 1989. AB - The presence of antibody to human immunodeficiency virus (HIV) in post-partum women may be inferred by screening the blood of their newborn babies, since maternal IgG antibodies freely cross the placenta. We tested a sample of 10,217 newborns from 10 hospitals covering three areas in Sydney and other metropolitan centres in New South Wales from April to July, 1989. None of the specimens gave a positive test for antibody to HIV. Thus, the prevalence of HIV positive serology in this sample of newborns was found to be zero. It was estimated that the seroprevalence of antibody to HIV among all neonates in the study area was between zero and 0.045% (99% confidence interval). Because newborns are an accessible group for the study of HIV, and can act as surrogates for their mothers, anonymous testing of this sentinel group will remove some of the limitations generalizing the information in the present database of HIV infection in Australia. This study provides baseline data and suggests that there is not a widespread epidemic of HIV infection among heterosexual persons in Australia at the present time and that routine antenatal testing of women for antibody to HIV may not be cost-effective. However, it will be important to repeat this study at regular intervals to detect any increase in HIV seroprevalence. PMID- 2215308 TI - Predicting the course of AIDS in Australia. AB - There have been urgent demands for knowledge about the epidemic of the acquired immunodeficiency syndrome (AIDS) in Australia. Accurate predictions are important for efficient allocation and planning of limited health-care resources. Ideal data for this purpose would be reliable knowledge of the past and present incidence of human immunodeficiency virus (HIV) infection. However, since the incidence of the infection is unknown predictions can only be based on historical data of the incidence of AIDS. In this article, we show the limitations of such predictions by examining a broad range of mathematical models that successfully track the observed data (1187 cases diagnosed to December 31, 1988). In addition, we describe a simple method for prediction in subgroups where the numbers of cases observed so far are small. Four models representing different forms of departure from the simple exponential model provide the best fits to the Australian AIDS data. Regional variability and a possible effect resulting from the introduction of zidovudine were incorporated into the models. Significant regional variability in the course of the epidemic was observed between New South Wales, Victoria and the rest of the country. For Australia as a whole, the doubling time changed from less than one year before mid 1987 to more than two years after this time. Model fits were improved by fitting the models to just the four years of data from 1985. The models give comparable predictions for the first year (1989) of around 600 new cases. However, by 1993 the predictions vary considerably, ranging from 500 to 2300 new cases. It is predicted that between 3100 and 6700 cases are likely to be diagnosed in Australia between 1989 and 1993. The results from the subgroup prediction demonstrate that when the observed number of cases is small, then the range of predictions for a future time interval is very wide. For reliable long-term predictions that are necessary for public health planning, basic information on the past and present incidence of HIV infection is urgently needed. PMID- 2215309 TI - Measuring the HIV epidemic: the Western Australian experience. AB - Previous discussion about sources of error in measuring the human immunodeficiency virus (HIV) epidemic has tended to emphasise errors which underestimated the number of HIV infected persons. Data are provided from Western Australia illustrating potential errors which may result in overestimating the size of the epidemic. Duplication of persons notified in more than one State and multiple notifications by doctors and laboratories of single cases may give rise to substantial errors in over-estimation. PMID- 2215310 TI - Clinical assessment and management of swallowing difficulties after stroke. AB - The purpose of this study was to investigate the frequency of swallowing disorders in patients with stroke referred for speech pathology, and to determine the outcome of therapeutic intervention based on presenting symptoms ascertained from clinical bedside assessment. The study was conducted over a 12-month period (1988) in a 191-bed acute-care hospital. Data on referral of patients with stroke to the Speech Pathology Department and frequency of swallowing disorders were analysed, and showed a referral rate of 61% for patients with stroke, with a 54% prevalence of swallowing disorders among referred patients. On discharge, 75.5% of patients who had exhibited swallowing disorders were on full oral diets. PMID- 2215311 TI - Pain 1990: VIth World Congress on pain. PMID- 2215312 TI - Mercury pigmentation and high mercury levels from the use of a cosmetic cream. AB - A 42-year-old woman presented with facial mercury pigmentation, raised levels of mercury in the blood and urine and possible neuropsychiatric toxicity after the topical application of 17.5% mercuric ammonium chloride. The patient purchased a mercury-containing cream without prescription from Victorian pharmacies for many years to lighten her complexion. She was unaware of any health risk. No warning appears on the package or insert of the cream she used. Health workers, particularly pharmacists and medical practitioners, should be aware that over-the counter mercury-containing creams may raise the concentrations of mercury in the blood and urine to potentially toxic levels. A warning on the package should be considered and use of the cream restricted. PMID- 2215313 TI - Eosinophilic enteritis presenting as surgical emergencies: a report of six cases. AB - Eosinophilic enteritis is now commonly diagnosed in northern Queensland, and cases have been seen elsewhere. The patients present with acute abdominal symptoms, which may mimic appendicitis, and many cases are managed by surgery. To facilitate the diagnosis of this unusual syndrome, six surgically treated cases are reported here. Blood eosinophilia may be a helpful diagnostic feature, but in some cases it does not develop until after the acute abdominal episode. Most cases resolve satisfactorily with conservative management. PMID- 2215314 TI - An acute pain service in an Australian teaching hospital: the first year. AB - The Acute Pain Service began at the Royal Adelaide Hospital in April 1989. Funding, education programmes, policies, procedures, protocols, techniques (particularly patient-controlled analgesia, epidural opioid analgesia and subcutaneous morphine therapy) and daily organisation of the service are described in this article, and the experience with the 1053 patients referred to the Service during the first year of operation is reported. The occurrence of major complications was small. Mild-to-moderate respiratory depression occurred in four (0.5%) of the 747 patients who received patient-controlled analgesia and in none of the 177 who received epidural opioids. Five patients receiving patient controlled analgesia had persistent nausea/vomiting; 320 (35%) of all patients receiving patient-controlled analgesia or epidural opioids suffered nausea/vomiting that required no treatment or was alleviated by treatment with an antiemetic. Around 13% of patients reported mild-to-moderate itching. In our experience, the combination of appropriately trained nursing and medical staff, standardised orders and procedures, and proper supervision can lead to safe, more effective management of acute pain. PMID- 2215315 TI - Nystagmus retractorius and progressive ataxia in a young man: clinicopathological conference. PMID- 2215316 TI - Mammography and the diagnosis of palpable breast cancer. PMID- 2215317 TI - Medical and government response to child abuse. PMID- 2215318 TI - The diagnosis of breast cancer. PMID- 2215319 TI - The changing scene of liver surgery. PMID- 2215320 TI - Sun protection in Illawarra schoolchildren. PMID- 2215321 TI - Oestrogen deficiency following pelvic inflammatory disease. PMID- 2215322 TI - Risk of transmission of the human immunodeficiency virus in the prison setting. PMID- 2215323 TI - Hepatitis B infection--a proxy measure of risk factors for HIV infection in IVDUs? PMID- 2215324 TI - General practitioners and "problem" drinkers. PMID- 2215325 TI - General practitioners' knowledge of HIV infection and AIDS. PMID- 2215326 TI - Abused doctors. PMID- 2215327 TI - Hair replacement surgery. PMID- 2215328 TI - Lymphoedema Association of Victoria. PMID- 2215329 TI - Thiamine in our bread and wine. PMID- 2215330 TI - The ethics of resource allocation. PMID- 2215331 TI - Problems facing the teaching hospitals. PMID- 2215332 TI - Selection of medical students. PMID- 2215333 TI - Are dietary goals and guidelines enough? PMID- 2215334 TI - Sociodemographic determinants in Australia of the intake of food and nutrients implicated in cancer aetiology. AB - In recent years, there has been a growing awareness of the role that diet can play in the promotion, retardation or amelioration of the cancer process. This has led to the development of dietary guidelines for cancer prevention by health authorities in several Western societies. However, there is still limited information about the sociodemographic determinants of intake of foods and nutrients of interest in many of these countries. A study of the dietary intake of a random sample of residents of the State of Victoria in Australia showed that women, those in the older age groups and in the higher occupational ranks, had diets more in line with current recommendations for cancer prevention--the most marked differences being between men and women. However, the sociodemographic differences were relatively small compared with the low rate of overall compliance with the guidelines. PMID- 2215336 TI - Emergency and after-hours work performed in country hospitals. AB - Country doctors perform emergency work in addition to their conventional general practice role. Over a one-month period 17 general practitioners in four Hunter Region towns recorded all emergency calls describing the time they were called, the severity of the patients' conditions, the skills used and the time taken. A scale to measure severity of illness was devised and tested for this purpose. There were 1197 emergency calls, mostly seen at the local hospital, either in the outpatients department or on the wards. They were unevenly distributed in time, with fewer calls at night, but the doctors were disturbed during nearly half of their nights on call. Of the calls 15% were for trivial reasons, 34% were for patients who needed standard general practice care, and 50% were for patients who needed the services of the hospital or were already inpatients. Most attendances were brief, but 15% took more than 30 minutes and some much longer. Counselling skills were used for 47% of patients and technical skills in 22%. The strain of the work involved and the disturbance of personal life justify extra payments to country doctors, and the adequacy of current pay schedules is questioned. However, the peculiarities of funding result in the State Health Department underwriting most emergency costs in country towns, whereas in the cities the Commonwealth Department of Health pays for a larger proportion, leading to concern about the high apparent costs of country hospitals. The information in this survey may help improve planning for training and remuneration of country doctors to help ease the current shortage. PMID- 2215335 TI - Ultrasound diagnosis of lower limb deep venous thrombosis. AB - Venous ultrasound imaging was compared with ascending contrast venography for the diagnosis of suspected deep vein thrombosis (DVT) in the femoral, popliteal and calf vein segments of 44 limbs in 44 patients. One femoral and one calf vein segment could not be imaged (1.5% of the segments examined), but during the same period venography failed in six patients because of an inability to cannulate a swollen limb. Ultrasound imaging compared with venography as a means of diagnosing DVT showed an overall sensitivity of 95% and a specificity of 92%. The sensitivity and specificity of ultrasound imaging for the diagnosis of both femoral and popliteal vein thromboses were 100% and 97%, respectively, and for calf vein thrombosis were 85% and 83%, respectively. This study supports the recommendation that ultrasound imaging is now the investigation of choice for the diagnosis of DVT provided that the scan is performed by an experienced vascular technologist. Ultrasound imaging may also define other pathological conditions presenting in the differential diagnosis of DVT, such as superficial thrombophlebitis and Baker's cyst. PMID- 2215337 TI - Infection with Mycobacterium avium complex in Australian patients with AIDS. AB - Data supplied by tuberculosis reference laboratories in Australia indicate that from mid-1985 to the end of 1988, 202 patients with the acquired immunodeficiency syndrome (AIDS) were diagnosed as having concomitant infection caused by organisms of the Mycobacterium avium complex. This figure represents 17.3% of all AIDS cases diagnosed. Serotyping showed that the majority of isolates were serovars of M. avium, namely serovars 1, 4 and 8. There is evidence of geographic differences in the dominant serovar. Of 45 patients with isolates from more than one site of the body, 17 (38%) were infected with at least two different serovars. The findings show the importance of disseminated atypical mycobacteriosis in patients with AIDS, and they provide data for use in defining the epidemiology and natural history of such infections. PMID- 2215338 TI - Prolactin and breast cancer risk. AB - A study of 424 women was undertaken to determine whether there was an association between serum prolactin levels and breast cancer; whether prolactin levels would reflect degrees of risk of developing breast cancer; and whether associations between known risk factors for breast cancer and serum prolactin concentrations could be demonstrated. Prolactin levels higher than the median value in control subjects were found to be associated with a more than two-fold increase in the risk of breast cancer (relative risk, 2.1; confidence interval [CI], 1.0-4.5). Moreover, a relative risk of 1.7 (CI, 0.9-3.3) for a group of women with benign epithelial hyperplasia (high risk of developing breast cancer), and a relative risk of 1.0 (CI, 0.6-1.8) for a group with benign fibrocystic disease (low risk of developing breast cancer), provided supportive evidence that prolactin plays a role in the development of breast cancer. A considerable fall in the concentration of prolactin at menopause was noted, so those women who have an early menopause have a reduced period of exposure to high concentrations of prolactin. Similarly, there was a considerable reduction in prolactin concentration after the first pregnancy. Finally, our results showed that, in premenopausal women, a high intake of saturated fats was associated with a high prolactin concentration. Our study supports the concept that parity, menstrual status, and saturated fat consumption influence a woman's exposure to prolactin and therefore the risk of developing breast cancer. PMID- 2215339 TI - Hypotension: assessment and management. PMID- 2215340 TI - Eosinophilia-myalgia syndrome associated with L-tryptophan use. AB - A young, previously healthy woman presented with increasing muscle pain, lower limb swelling, fatigue and eosinophilia. She had consumed L-tryptophan tablets (one to two at night) over the preceding five months for management of her insomnia. Her condition slowly deteriorated and she developed generalised oedema and severe lethargy. A white blood cell count was 21.3 x 10(9)/L with 43% eosinophils (Normal range: 4.0-11.0 x 10(9)/L with 1-6% eosinophils. A biopsy specimen of the deep fascia and gastrocnemius muscle demonstrated fasciitis and myositis. The patient failed to recover after cessation of L-tryptophan use but her condition improved rapidly without significant sequelae after systemic treatment with corticosteroids. PMID- 2215341 TI - The turtle's revenge: a case of soft tissue Mycobacterium chelonae infection. AB - A case of cutaneous Mycobacterium chelonae infection with sporotrichoid spread and extensive antibiotic resistance is presented. Control of this problem was only achieved after extensive debridement and grafting of the involved limb. The importance of surgery in management is discussed and the literature is reviewed. PMID- 2215342 TI - Lightning strikes. AB - Lightning strike is a natural phenomenon with potentially devastating effects. The physics of lightning strike and the physiology of lightning injury are discussed. Three cases are reported and the clinical features are described. Aspects of the management of such patients are discussed with particular emphasis on assessment and resuscitation in the Emergency Department. PMID- 2215344 TI - Highly selective vagotomy in the treatment of complicated duodenal ulcers. PMID- 2215343 TI - Aconite poisoning. PMID- 2215345 TI - Some solutions to the shortage of general practitioners in rural Australia. PMID- 2215346 TI - Which anti-smoking programme? PMID- 2215347 TI - Alcohol taxes: the case for reform. PMID- 2215348 TI - Reducing agents and AIDS--why are we waiting? PMID- 2215349 TI - Pertussis notification. PMID- 2215350 TI - Risk of parasitic infections from sandpits. PMID- 2215351 TI - The injecting and sexual behaviour of intravenous drug users in Sydney. PMID- 2215352 TI - Sudden infant death syndrome and consumptive coagulopathy. PMID- 2215353 TI - Acute reactions to drugs of abuse. PMID- 2215354 TI - Efficient expression of chicken alpha 1(VI) collagen chain in transiently transfected mammalian cells. AB - Type VI collagen is a component of the extracellular matrix made of three subunits, alpha 1(VI) and alpha 2(VI) (Mr = 140,000), and alpha 3(VI) (Mr = greater than 300,000). Triple helical monomers assemble intracellularly into disulfide-linked dimers and tetramers, with the tetramers being the "building blocks" that give rise to higher order extracellular structures by head-to-head association, the microfilaments. To study the pattern of assembly and the structure-function relationships of type VI collagen, we transfected mammalian cells with a full-length cDNA coding for chicken alpha 1(VI) under the control of SV40 early and late promoters and assayed the expression, secretion, and assembly of the protein by immunoperoxidase and immunoprecipitation of metabolically labeled cells. First, conditions were determined that allowed efficient transfection both in African monkey kidney COS-1 and CV-1 cells and in mouse fibroblasts. In our hands the late promoter was most efficient in CV-1 cells; whereas the early promoter was efficient in L cells at three days post transfection. Chicken alpha 1(VI) could be isolated from cell extracts as well as from cell medium. Both the intracellular and the secreted forms of alpha 1(VI) are present as a monomer polypeptide and as disulfide-linked dimers and trimers that migrate in SDS gels with apparent Mr of about 130,000, 240,000 and 360,000, respectively. In L cells, endogenous mouse type VI collagen also was isolated by immunoprecipitation with specific antibodies. However, heterologous molecules made of the chicken alpha 1(VI) chain and the mouse alpha 2(VI) and alpha 3(VI) chains were not detected in the present experiments. Digestion with pepsin of the non-reduced chicken alpha 1(VI) polypeptides immunoprecipitated from the cell medium resulted in the disappearance of the bands, suggesting improper or non stable assembly of alpha 1(VI) homotrimers. These data support predictions from sequence analysis that type VI collagen heterotrimeric molecules are more stable than other assembly alternatives. PMID- 2215355 TI - Effect of static stretching on elastin production by porcine aortic smooth muscle cells. AB - An in vitro model was developed to assay the effects of static stretching on soluble elastin (tropoelastin, TE) synthesis by porcine aorta smooth muscle cells (SMC). Culture dishes containing SMC adherent to the deformable bottoms were placed over hard convex templates. Stress was applied by placing a weight on the dish covers. Measurement of TE was accomplished by a specific ELISA assay. With this model we demonstrated reproducible stimulation of TE synthesis by stretched SMC. Significant results (161.4% of control; p = less than 0.003 by Student's t test) were obtained by stretching passage 2 SMC for 3 days with a medium change after the first 18-24 hours, use of 5% newborn calf serum in cultures during stretching, and 50-g weight. DNA content in stretched cultures did not increase over control values. Thus, stretching alone did not cause hyperplasia or hyperploidy in these SMC and, in the absence of other vascular cell elements, was sufficient to increase production of this extracellular matrix protein. Transduction of mechanical force into elastin gene expression by SMC may contribute to the development of thickened arterial tunica media characteristic of hypertensive vessels. PMID- 2215356 TI - A highly specific and quantitative method for determining type III/I collagen ratios in tissues. AB - The distribution of type I and type III collagens in rat, bovine and human skin were examined by a quantitative 2-D CNBr peptide mapping method. The procedure involved the solubilization of tissues by digestion with CNBr, radioactive labeling in vitro by [3H]-NaBH4 in dimethylformamide, reduction by mercaptoethanol, a second CNBr digestion and 2-D (isoelectric focusing and NaDodSO4 electrophoresis) mapping. The amounts of type I and type III collagen peptide spots in the fluorographs of 2-D maps were analyzed by 2-D scanning densitometer/analyzer. Mixtures containing various ratios of purified type I and type III collagen were used to obtain a standard curve. Using this procedure we were able to determine that in adult human skin (age range 35-65 years) 22% (+1.3%) of the labelled collagen is type III. This value is significantly higher than that was previously estimated by less accurate methods. PMID- 2215357 TI - Alteration of collagen composition and cross-linking in keloid tissues. AB - Collagen composition and cross-linking in human keloid and normal skin tissues were analyzed biochemically. CNBr peptides were separated by 2-dimensional (2-D) mapping and high performance liquid chromatography (HPLC). The amounts of type I and type III collagen was quantified by 2-D scanning densitometry of fluorographs of 2-D maps derived from samples radioactively labelled in vitro by [3H]-NaBH4 in dimethylformamide. Keloid tissues contained 31.6 +/- 2.2 percent type III collagen as compared to 21.4 +/- 2.7 percent type III present in normal human skin dermis. HPLC profiles of CNBr peptides showed that approximately 5 percent of the high molecular weight material in keloids is mercaptoethanol reducible, compared to insignificant amounts in normal skin. 2-D maps derived from CNBr peptides of keloid collagen demonstrated thiol reduction sensitive alpha 1(III) CB9 dimer as well as 24,000- and 32,000-dalton CNBr peptides, which were not mercaptoethanol reduction sensitive in normal skin due to cross-linking via the lysyl oxidase pathway. Also, a group of 20,000- to 25,000-dalton CNBr peptides, in the alpha 1(I)-CB6 cross-linking region were prominent in keloid tissues. PMID- 2215358 TI - The susceptibility of elastin-fatty acid complexes to elastolytic enzymes. AB - Elastin in vivo is likely to be complexed with amphipathic ligands such as lipids. The susceptibility of stable [3H] elastin-fatty acid complexes to the action of porcine pancreatic elastase (PPE) and to human neutrophil lysates over time was assessed. Elastolysis by PPE of substrates prepared with oleic or linoleic acids was initially higher (for up to 2 hours) than that of uncomplexed elastin. Stearic acid and elaidic acid (the trans isomer of oleic acid) did not enhance the elastolytic rate above control. The stimulatory effect of oleic and linoleic acids appeared to derive from increased adsorption of PPE onto elastin; the loss of stimulatory activity over time occurred in parallel with a progressive decrease in adsorption. All fatty acids tested inhibited elastolysis by neutrophil lysates, the effect being particularly marked with oleic and elaidic acids. These results indicate that 1). Complexed fatty acids can modulate the rate of elastin breakdown by elastases; 2). The effects observed with PPE are due to differences in adsorption of enzyme onto substrate, possibly as a result of steric considerations; 3). Since elastolysis by neutrophil lysates is inhibited by all fatty acids, the properties of different elastolytic enzymes should be considered in in vitro model systems of connective tissue breakdown. PMID- 2215359 TI - Moderately severe osteogenesis imperfecta: biochemical studies showing variable defect localization in the triple-helical domain of type I collagen. AB - This report describes the biochemical investigations on six patients affected by a moderate form of Osteogenesis Imperfecta (type IV according to the Sillence classification). Biochemical characterization of type I collagen produced by skin fibroblasts showed considerable heterogeneity: in three patients out of six, collagen appeared normal; while in the three others a structural defect in the protein was present. In these probands the mutations were localized in different regions of the triple helix domain (corresponding to peptides alpha 1(I)CB6 and alpha 1(I)CB7). In two probands showing the defect in alpha 1(I)CB7, a decrease of the thermal stability of the protein was present. PMID- 2215360 TI - Preparation of a hospital rehabilitation system for war and other disasters. AB - A large number of casualties caused by war are in need of medical rehabilitation. Rehabilitation facilities are unable to cope adequately with them without advance planning and preparedness. Guidelines are suggested for the planning and preparation of a hospital rehabilitation system for war, including the formulation of policies, expanding and strengthening of existing rehabilitation facilities, and converting institutions, as well as securing the necessary human and material resources. It is also suggested that such plans and preparations should be adapted to form a basis for meeting rehabilitation needs caused by natural and civil disasters. PMID- 2215361 TI - Low-level radiation--how dangerous is it? AB - The main delayed effect of ionizing radiation in the individual is the induction of cancer. However, for low doses (less than 100 mSv effective dose equivalent), there is no direct evidence of radiation-induced cancer, with the possible exception of childhood cancer following prenatal exposure to X-rays. The risk at low doses has to be estimated from the observed risk at high doses; there are considerable uncertainties in this extrapolation. Direct study of those exposed to low doses does not produce any more precise information, although it does impose boundary conditions on the risk. Currently the most important problem in environmental radiation exposure is the increased incidence of childhood leukaemia observed around some nuclear installations; the explanation for this remains unclear. PMID- 2215362 TI - The Nazi doctors and the Nuremberg Code: relevance for modern medical research. PMID- 2215363 TI - The condition of health services in the Gaza Strip. AB - The Association of Israeli and Palestinian Physicians for Human Rights was established during the first months of the uprising, against the background of a severe situation in which people were killed and wounded daily. AIPPHR works for the protection of human dignity and human life; defending physicians and patients in a state of political conflict out of loyalty to the principles of universal morality which constitute an inseparable part of the medical profession. This report, which is the result of months of research and investigation, is aimed, among other purposes, at bringing reliable information to the knowledge of the medical community in Israel and the Israeli Medical Association (IMA)--the body which organizes them. The silence of the medical community in the face of the phenomena described above is foreign to the spirit of doctors and medicine. The association's activity is aimed at creating a change in this situation out of the belief that the silence on the part of a large section of the medical community in Israel stems from a lack of regular and reliable information. In order to describe the situation of the medical services in the Gaza Strip, one must note two contrasting trends: on one hand, there is advancement in the population's health conditions, which is expressed by a decline in the infant mortality rate (from 86/1000 in 1970 to 28.1/1000 in 1988); a decline in the number of cases of whooping cough among children (30.1 in 1970 in contrast to 0 in 1988); and a decline in the number of cases of polio (14.3 in 1970 in contrast to 1 in 1980). On the other hand, the tendency of stagnation must be noted, especially in the development of independent local health services. Medicine in the Gaza Strip has been during the entire period of the occupation, and remains, completely dependent on Israeli medicine. Modern equipment and modern medical technology have been at the service of the residents of the Gaza Strip in Israeli hospitals, but they were not given the chance to develop high-standard medicine in their own hospitals. The Gaza Strip population has no representation at the decision-making level on issues of budget, development and distribution of resources--which are completely in the hands of the Civil Administration and the Israeli authorities. During the uprising there was a steep rise in medical needs. Residents in need of medical services are completely dependent on the decisions of the military government and the state leadership and the giving of these services is tied to political, not medical/professional policy. Since the beginning of the uprising in the Occupied Territories, a new tendency has appeared; the use of medicine as an additional means of repression against the population. This means that medicine has been removed from the status of a basic human right and recruited as a means of punishment. This is a phenomenon which no physician or person of conscience can accept. PMID- 2215364 TI - Joseph Riviere: physician and peaceworker. AB - In 1905, Dr Joseph Riviere, a graduate of the Paris Medical Faculty, founded the International Medical Association against War (IMAW). By 1914 IMAW had members in over 40 countries. This paper looks at the work of Dr Riviere, both as physician and peaceworker. PMID- 2215365 TI - [An experimental quantitative assessment of the efficiency of Borrelia persica transmission by Ornithodoros papillipes ticks. 1. 2 forms of borreliemia in guinea pigs]. AB - Experimental borreliosis in guinea pigs caused by ticks' bites assumed two forms- typical and mild, the latter being encountered in 40% of cases. Mild form significantly differs from the typical one in some indices of borreliemia: intensity, duration, time of onset and cessation, absence of fluctuations in the number of borrelia. The form is not easily diagnosed by the analysis of animal blood preparations, which should be taken into consideration in experimental and clinical practice. In mild form of borreliemia the agent should be searched for in the blood of guinea pigs daily from days 6 to 12 after the infection, with the following control till day 20. PMID- 2215366 TI - [The lysozyme of Ixodes persulcatus ticks]. AB - Using a technique based on specific enzyme sorption by chitin (beta-1-4-N acetylglucosamine), lysozyme with a molecular mass of 15,000 has been isolated from homogenates of the Ix. persulcatus ticks. Micrococci and staphylococci proved to be most sensitive to lysozyme from the Ix. persulcatus ticks, while E. coli and Salmonella were less sensitive. The minimum inhibitory concentration of lysozyme from Ix. persulcatus was 2-4 times lower than that of egg lysozyme. Lysozyme from the Ix. persulcatus ticks is resistant to heating in acid medium and loses some of its activity in alkaline medium. The loss of the activity in the both media is somewhat lower than that of egg lysozyme in analogous conditions. PMID- 2215367 TI - [The achievements and outlook in the control of helminthiases in Bulgaria]. AB - The paper describes organization and achievements of the struggle against human helminthiases over a 30-year period in Bulgaria. Over this period, in Bulgaria Taenia solium was eradicated, while the incidence of taeniasis, ascariasis, trichocephaliasis, hymenolepiasis, enterobiasis and ascariasis, trichocephaliasis, hymenolepiasis, enterobiasis and echinococcosis was reduced several-fold. The authors suggest effective measures for the struggle against other helminthiases in the following 5-10 years. PMID- 2215368 TI - [The structure of the geographic range of opisthorchiasis and the tasks in controlling this invasion]. AB - Our own investigations in the Yenisei, Ob, Dnieper, Northern Dvina river basins and the analysis of the literary data served as the basis for establishing the relationship between the area of the pathogen dissemination and the area of opisthorchiasis distribution (the map scheme is attached). 4 degrees of endemicity characterized by quantitative indices of general affection, children's infestation, the invasion intensity and manifestation have been suggested as a criterion for division of territories into regions. The map of 3 territories in the Dnieper River basin (the Ukraine) most unfavourable for opisthorchiasis is presented. According to the endemicity, differential anti-invasion goals and measures are suggested. PMID- 2215369 TI - [Ecological approaches to the study of natural-focus diseases]. AB - Changes in the epidemiology and epizootiology of diseases with natural foci due to anthropogenic influence on biosphere necessitate thorough studies of ecological specific features of agents, carriers and vertebral hosts reflecting their adaptation to various natural geographical and social conditions. The attention should be focussed on geographical variability of agents, changes in populations of arthropod carriers and their feeders, monitoring of natural territorial complexes and scientifically grounded prognosis for diseases with natural foci. PMID- 2215370 TI - [The effect of specific treatment on the function of the small intestine in opisthorchiasis]. AB - The anthelminthic agents chloxylum and prasiquantel were examined for their effects in patients with an above 5-year history of Opisthorchis invasion. The van de Kamer procedure revealed that chloxylum produced an inhibitory effect on absorption of d-xylose and fat. Prasiquantel failed to impair the absorptive function of the small intestine. Helminthological curing in patients with chronic opisthorchiasis was not shown to normalize dysfunction of the small intestine. PMID- 2215371 TI - [The similarity of the biological effects from the parenteral administration of ascarid antigenic complexes and Salmonella typhi endotoxins]. AB - The experiment with rabbits showed that it was basically possible to develop local and generalized Shwartzman's phenomenon under the combined effect of ascaris antigens and typhoid bacterial endotoxins. Intracutaneous (0.2 ml.) or intravenous (0.1 ml/kg) sensitization of animals by ascaris antigens or microbe endotoxins after repeated intravenous crossover, intravenous injection of the antigens used to result in the development of classical local and generalized Shwartzman's phenomenon. PMID- 2215372 TI - [Antibody-dependent cell-mediated immune reactions in experimental trichinelliasis in mice]. AB - The experiments on mice experimentally infected with Trichinella larvae have established that in mild infection adhesive and killer cell reactions developed on day 14, reached their maximum on days 21-30 and began to attenuate on day 45. The cells from animals with moderate infection showed a higher immune activity which remained unchanged till day 90 of infection. The cells from mice with severe infection showed inhibition of immune activity which was most marked on days 21 and 30 of the infection. Eosinophiles and neutrophils are characterized by IgE-dependent cell adherence and killing activity, the involvement of macrophages in the responses seems to be insignificant. PMID- 2215373 TI - [Obstructive jaundice in a rupture of echinococcal cysts into the bile ducts]. AB - 130 patients with obstructive jaundice were examined for break of liver hydatids into the biliary ducts. Types of jaundice and break, frequency of fistula sites and clinical picture are described. The surgical interventions are outlined, and the results of their application are studied. PMID- 2215374 TI - [The problem of the carcinogenicity of parasites]. AB - Based on the reported data and their own experience the authors defined the role of carcinogenic parasites in tumorigenesis as promoters. The investigators supposed that a many-year invasion that caused a permanent proliferation of cellular elements and immune suppression were the criteria for carcinogenicity of parasites. PMID- 2215375 TI - [The status and outlook of the study of blood-sucking Diptera in the Urals and adjacent territories]. AB - The knowledge accumulated in the course of studies of bloodsucking dipterans: mosquitoes, horseflies, Heleidae, midges in the Urals and the adjacent territories is reviewed. The prospects of complex approaches to problems of bloodsucking insects are discussed. PMID- 2215376 TI - [Factors that determine the possibility of tick-borne encephalitis infection. 3. The probability of human contact with an infected vector in the central taiga forests of Khabarovsk Territory]. AB - Contacts with Ixodes persulcatus Sch. and the carriers' infestation with encephalitis virus have been studied for many years in middle taiga forests of the Khabarovsk Territory. The results of the studies have been compared. The risk of contacts with ticks invaded with varying virus doses has been assessed. It has been established that clinical forms of the disease develop upon bites of highly infected ticks. The number of such ticks in the natural focus is an important index of its potential danger. This must be taken into consideration as the most important factor of possible infection and used as a real index in the modelling of an epidemic process. PMID- 2215377 TI - [Ways and methods of searching for new anthelmintics]. AB - The ways of searching for new anthelminthic agents among diverse chemical compounds are analysed. The most promising chemical groups are presented. It is recommended to test every drug using as many as possible experimental models. For drug screening it is advisable to apply a multi-stage investigation method as the most economic and perspective one. The drug selection technique, experimental study procedure and ways of increasing anthelminthic efficiency are outlined. PMID- 2215378 TI - [New data on tick-borne rickettsiosis in Novosibirsk Province]. AB - New, so far unknown epidemically active natural foci of tick-borne rickettsiosis have been identified in Suzun District, Novosibirsk Province. The patients had a typical clinical pattern and epidemiological history of the disease. The cases were recorded in a number of communities in the northern forest-steppe zones. The results of the epidemiological survey and rickettsial studies of Ixodes ticks and blood sera of farm animals demonstrate the existence of clear-cut natural foci of tick-borne rickettsiosis, with its main vectors being ticks D. silvarum. The infestation of ticks was proved by biotests in passive hemagglutination tests, using an immunoglobulin diagnostic kit. Some measures for the monitoring of foci and disease prevention are suggested. PMID- 2215380 TI - [The first cases of Lyme borreliosis in Lithuania]. AB - In 1987, 3 typical fresh cases of Lyme's borreliosis were first diagnosed in Lithuania. The cases were serologically confirmed and cured. Brief clinical description of the cases is presented. PMID- 2215379 TI - [Antigen isolation from the blood of patients with malaria for its serological diagnosis]. AB - A relatively high sensitivity and specificity of indirect enzyme immunoassay using the antibody obtained from the blood of patients with P. falciparum-induced malaria in the acute period have been demonstrated. The substrate for antigen isolation is available and can be easily obtained in sufficient quantities. PMID- 2215382 TI - [On the centenary of the birth of M. G. Rashina (1889-1989)]. PMID- 2215381 TI - [The first cases of human cryptosporidiosis in Moscow]. AB - Feces samples received from 438 children, aged 1 month to 10 years, from Moscow who were admitted to hospital in June-August 1989 for acute intestinal disease, were examined for cryptosporidium oocysts. Cryptosporidium oocysts were found in 16 samples (8 boys and 8 girls), which accounted for 3.65%. The smears were stained by a modified Ziehl-Neelsen technique, concentration methods were not applied. PMID- 2215383 TI - [The epidemic manifestation of natural foci of tick-borne encephalitis in the Maritime Territory. 1. The range structure of the morbidity]. AB - Using a computed mapping technique, specific features of the epidemic process have been established in the Maritime Territory endemic for tick-borne encephalitis. The most active natural foci of tick-borne encephalitis have been discovered in the Sikhote-Alin Mountain range. PMID- 2215384 TI - [Stereological analysis of the vascular network of the ganglionic eminence and the corpus striatum during brain development in man]. AB - A study of the volume density of the ganglionic eminence vascular network and the constituent parts of the corpus striatum was performed on 8 chosen foetal brains, which were well-injected with a mixture of India ink and gelatin, aged from 14-25 postovulatory weeks. The volume density of the ganglionic eminence vascular network amounts to 0.0209-0.0300 mm0, of the caudate nucleus to 0.0131-0.0181 mm0, of the putamen to 0.0136-0.0159 mm0, and of the globus pallidus to 0.0121 0.0159 mm0. The comparison of the results obtained, shows that the volume density of the ganglionic eminence vascular network is higher than the volume density of the other examined structures and that this difference is statistically highly significant (p less than 0.01). The augmented volume density of the ganglionic eminence vascular network points to a possibility of slow blood flow through its vascular bed, which was experimentally demonstrated on animals. This slow blood flow, among other factors, may be the cause of a ganglionic eminence venous infarction in premature newborns of low birthweight. PMID- 2215385 TI - [Inhalation scintigraphy in the diagnosis of pulmonary thromboembolism]. AB - The purpose of this report is to realize the role of inhalation scintigraphy in the diagnostics of the pulmonary thromboembolic disease, as an addition to perfusion lung scintigraphy in the assessment of the nature of perfusion disturbances discovered by the perfusion scintigram. Perfusion lung scintigraphy, in itself, is a very sensitive indicator of a recent pulmonary thromboembolism but it is not sufficiently specific. The combining of perfusion and inhalation lung scintigraphy increases the specific quality of scintigraphic examinations in the diagnostics of lung thromboembolism. PMID- 2215386 TI - [Histochemical characteristics of the adrenal glomerular zone 180 days after discontinuing the effects of a detergent]. AB - The substance of this paper is the study of the histochemical characteristics of the glomerular zone 180 days after the termination of detergent influence. The presence of neutral lipids, triglycerides, phospholipids and nucleic acids was analyzed. The decreased quantity of certain fatty substances, as well as the increased quantity of nucleic acids were considered, in the light of our previous studies, as the first signs of glomerular zone cell function normalization in the adrenal cortex. PMID- 2215387 TI - [Case report of pheochromocytoma with an atypical localization]. AB - One of the endocrine causes of arterial hypertension is pheochromocytoma, usually located in the adrenal gland medulla. Extra-adrenal tumor locations are seldom encountered, and this can considerably complicate the diagnostic procedure. If a distinct clinical manifestation exists, supported by the finding of elevated catecholamine values, it is essential to persistently and carefully search for the place of their increased production. Such an attitude is completely justified in regard to the knowledge that this endocrinologically conditioned hypertension can be permanently and successfully solved with a surgical procedure. A case of pheochromocytoma has been presented with an atypical mediastinal location, prolonged and complicated diagnostic procedure, which has been successfully solved by surgery. PMID- 2215388 TI - [Case report of a patient with psychomotor epilepsy and paranoid psychotic episodes]. AB - This paper gives a brief review of psychomotor epilepsy, one of the most common forms of epilepsy manifestations. The psychopathology which is seen with psychomotor epilepsy includes the greatest part of known pathological psychic manifestations with epilepsy in general. Here, a patient is presented with psychomotor epilepsy since his youth. In the last eight years, psychotic manifestations appear with him from time to time, they are not related with epileptic seizures, and phenomenology-wise, the clinical manifestation is that of paranoid schizophrenia. In the end there is a stress on differential diagnosis hardships in the telling apart of epileptic psychoses without mind disorders from endogenic psychoses. PMID- 2215389 TI - [Determination of nutritional levels in patients on chronic hemodialysis programs using anthropometric methods]. AB - The results of a number of methods used in the cross-sectional nutritional assessment differ markedly in patients on regular hemodialysis (RHD). Correlations of nutritional parameters were investigated in 31 patients on RHD and in 31 control subjects with similar sex and age structure without any considerable difference in any of the examined nutritional parameters. In the patient group on RHD, beside a high mutual correlation of general nutritional parameters and a high correlation of general parameters with fat compartment parameters and the fat free compartment (protein) parameter, there is also a high correlation of fat parameters with the protein parameter which does not occur in the control group. This can possibly explain the difficulties in the nutritional assessment of patients on RHD. Out of this reason we suggest the usage of the RBM/F classification which is a combination of relative body mass values (RBM) and the body fat content (F) percentage. PMID- 2215390 TI - [Characteristics of psychomotor organization in children]. AB - In the neurological examination of the child, there is a growing significance of subclinical semiotics and graphomotor expression. These discrete neurological signs give information about the maturity of complex motor organization and enable the following of cortical structure organization. Subclinical neurological semiotics in the form of muscular hypotonia, synkinesis and disturbed reciprocal coordination of movements at a certain age, present a physiological, developmental appearance, while at a later age they are a sign of immaturity, or of an organic neurological structure damage. PMID- 2215391 TI - [Methodologic characteristics of the radioreceptor test for insulin on erythrocytes]. AB - Presented, are the results of the characteristics testing of the radioreceptor test for insulin on erythrocytes (precision, reproductiveness and linearity). Our own modification of the method was used. Testing was done on erythrocytes from the same bottle of preserved blood. The following results were received: the used method is precise enough (correlation coefficient from 3-15%), reproductive (correlation coefficient about 15%), and linear (linear correlation coefficient 0.83) in a wide range of erythrocytes. These characteristics allow the use of the applied radioreceptor test in practice. PMID- 2215392 TI - [Smell perception in smokers]. AB - The author studied the changes of olfactory function in smokers. He established the fact that the threshold of the perception of smell increases in smokers. By studying the subjective experience of the intensity of smell he established an appearance which he named olfactory recruitment, the increased growth of smelling sensitivity, which points out the changes, not only on the olfactive mucous membranes, but on the olfactive paths as well. The author concludes that smoking influences the decrease of the function of smell and emphasizes the necessity of advising the stopping of smoking in the treatment of all types of smelling disorders, as one of the important elements of treatment. PMID- 2215393 TI - [Tissue damage caused by neutrophil granulocytes]. PMID- 2215394 TI - [Surgical treatment of cervical and vaginal cancer by means of the synchronized extraperitoneal-vaginal radical operation and the neovagina technic using the peritoneum]. AB - In the period from 1976 to 1986 we operated 350 cases by the technique of combined extraperitoneal-vaginal radical synchronized hysterectomy in cases of uterus and vagina cancer. We analyzed 236 cases and compared them with the control group operated by the technique of Wertheim and modifications. There is a considerable difference in operative and post-operative complications. There are less complications in the examined group of patients operated by the technique of combined synchronized extraperitoneal-vaginal radical operation. We introduced the technique of partial neovagina formation at the place of the resected one, by means of the anterior and posterior plica peritoneum by which we are able to preserve the normal length of the vagina. By the means of this technique we operated 21 patients; out of that 15 were with cancer of the uterus cervix, 6 with vagina cancer, and in 3 of them, a complete vaginectomy was performed, and a complete neovagina made. PMID- 2215395 TI - [Results of multiphasic oncology screening of the population in the community of Beej 1986-1987. II. Questionnaire screening]. AB - In the framework of the multiphase oncologic population screening in the community of Becej in the period from 1986-1987, the inquiry screening comprised 16,895 persons, whereby the following results were obtained: two malignant breast neoplasms, one uterine corpus neoplasm, one carcinoma of the larynx, and out of the non-target locations, not included in the specific questionnaire, there was one carcinoma of the lower lip and one malignant neoplasm of the salivary gland. Besides, 10 benign breast neoplasms and 12 benign uterine neoplasms were also detected. These specific results lagged behind the expected ones on the basis of the known average incidence and mortality in locations of Vojvodina included by this questionnaire. The elucidation of all possible causes leading to this disaccordance, was the task of specific studies intended for the improvement of this questionnaire as a method for the early detection of malignant and premalignant lesions. Other numerous mass pathological states were detected during the screening of either the characteristic signs of specific malignant neoplasm locations, or of risk factors of particular importance for the appearances of these malignant neoplasms. These health problems with clarified epidemiological dimensions in the population studied, necessitated planned solution according to the accepted doctrinary principals (protocols). Data on these diseases gave new dimensions to the inquiry (and the overall multiphase) oncologic population screening. The target-health educational effect of this inquiry which reached every man over 40 years of age in the population studied should not be neglected, either. PMID- 2215396 TI - [The significance of the determination of apoproteins in the diagnosis of lipoprotein metabolism disorders]. AB - The study, in the first place, describes the basic physical, chemical and biological characteristics of the most important apoprotein classes and their role in the metabolism of certain lipoprotein fractions. Special regard is given to the significance of determining particular apoproteins in the serum and in some lipoprotein fractions for the detection of particular disorders in lipoprotein metabolism. PMID- 2215397 TI - [Morbidity and mortality in adolescents in Vojvodina]. AB - Adolescents. The aim of this study was to analyze the morbidity and mortality of adolescents in SAP Vojvodina. For the analysis, data was used from the statistical yearbooks on the health protection of the population and data from individual statistical reports. The period from 1980 to 1986 was observed. In order to more easily follow the morbidity and mortality, and for a better insight into the pathology, the adolescents were divided into 2 age groups; the younger one from 10 to 14 years of age, and the older one from 15 to 19. Adolescents in Vojvodina mostly ail from respiratory diseases, illnesses of the digestive tract, and infective diseases, but a significant role in the morbidity is also taken by injuries and poisoning. Adolescents of the age group from 10 to 14 years, get sick more often. In SAP Vojvodina 156 adolescents die annually. The highest mortality is due to injuries and poisoning (16.36/1,000,000), and after that comes the mortality due to neoplasms (5.84/1,000,000), and the diseases of the respiratory and circulatory system (3.5/1,000,000). Mortality is higher in the adolescent group from 15 to 19 years of age. With this study only a partial insight was achieved into the pathology of the adolescent age group. In order to attain a full insight, it is absolutely necessary to actively and prospectively follow the health state of adolescents and the conditions of environment. PMID- 2215398 TI - [Occupational damage and risk of occupational damage in personnel working with "Amerika" and IGK "Polet" drying kilns in Novi Becej]. AB - The paper briefly presents the technological process and professional noxiousness in the working environment, exposed to which are the workers employed in the smoke house type "America" IGK "Polet" in Novi Becej. Described is a case of accidental poisoning of 28 working women with carbon-monoxide, which happened because of a malfunctioning valve, and the letting through of gases into the air for the smoke house. A presentation is given of all the undertaken preventive measures for preventing the possibility of the exiting of gases into the smoke house air by introducing a system for the continuous measurement of carbon monoxide concentrations in the working environment with sound and light signalization; the necessity of conducting periodical medical examinations of employees and examining of working environment conditions. PMID- 2215399 TI - [Doyne's honeycomb choroiditis]. AB - This paper describes the retinal changes of 11 parents whose children had the typical clinical manifestation of Doyne's honeycomb choroiditis. In 7 cases, the nonexudative ("dry") form of senile macular degeneration was discovered, 3 of these had increased number of drusen, and 4 of them were with large and confluent drusen, often with scattered pigmentation. Three parents had the exudative hemorrhagic form, and 1 parent had a cicatricial form of senile macular degeneration. Since Doyne's honeycomb choroiditis is transmitted with the autosomal dominant trait of inheritance, it is indirectly established that Doyne's honeycomb choroiditis progresses into one form of senile macular degeneration, and that senile macular degeneration is partly genetically determined. PMID- 2215400 TI - [Prevention of decubitus, edema, contractures]. AB - This paper presents a historical reminder of the development of medical care, a contemporary consideration of the division of care, as well as the definition of the term-quality medical care, and a review of the preventive measures for bed sore, edema and contracture. In regard to the fact that care and therapy are a tightly bound process, they must also be applied as such. The definition of the term-quality medical care is an open question. The prevention of bed-sore, edema and contracture is the element of quality care. PMID- 2215401 TI - [The first scientific meeting in Subotica--August 27-31 1899]. AB - The author brings out a brief survey of the development of Subotica as a city, and the development and achievements in it on a social and cultural scale during the 18th and 19th century. He states, that in the last decades of the past century, Subotica was a very strong economic and cultural center of this part of Vojvodina. Such a surrounding was offered, and afterwards it was decided upon, to organize an elite, professional and scientific manifestation--The Annual Meeting of Physicians and Naturalists of that--time Hungary. Here is an account of this First Scientific Meeting in Subotica, which was just the 30th Jubilee Meeting of the Physicians and Naturalists of Hungary. About 100 scientists took part in the work of this meeting, and 74 reports were presented. The holding of such a meeting in Subotica is, no doubt, an important moment in the cultural life of Subotica, and an especially important date in the development of the health service and science within it. PMID- 2215402 TI - [New possibilities in the semiquantitative examination of urine]. PMID- 2215403 TI - On the technique of extrapolation to obtain wall correction factors for ion chambers irradiated by photon beams. AB - Wall correction factors, which correct ion chamber response for photon attenuation and scatter, can differ by as much as 1.0% for spherical chambers depending on whether they are obtained experimentally by extrapolation measurements or by Monte Carlo simulation. This difference is not explained by experimental or calculational statistics which lie in the range 0.05%-0.2%. In this paper it is demonstrated that linear extrapolation of experimental data for spherical chambers is inappropriate, owing to the curvature of the chamber walls. A simple nonlinear theory is constructed that resolves the difference. The Monte Carlo calculations and the nonlinear theory are compared with extrapolation measurements for the NIST (formerly NBS) spherical chambers. It is concluded that wall correction factors should be obtained by Monte Carlo calculation for spherical chambers and that linear-extrapolation techniques should be regarded with suspicion for all chambers. PMID- 2215404 TI - Extending the concept of primary and scatter separation to the condition of electronic disequilibrium. AB - A major deficiency of current photon calculation methods that are based on the concept of primary and scatter separation is their inability to handle the condition of electronic disequilibrium. This deficiency is examined and it is shown that the limitation is not inherent in the algorithms themselves but is, at least in part, in the data which the algorithms use. A new concept of primary and scatter separation is developed to cover the condition of electronic disequilibrium. This new concept requires little change to the existing algorithms and only additional data are required, which are generated using Monte Carlo calculation methods. The new concept is tested using programs in the Theratronics Theraplan treatment-planning system, and two calculation examples illustrate the ability to model electron transport and also the improvement over the existing algorithms. Close analogy of the extended concept with the convolution/superposition method of dose calculation is also indicated. PMID- 2215405 TI - Comparison of ferrous sulfate (Fricke) and ionization dosimetry for high-energy photon and electron beams. AB - Dose measurements using Fricke and ionization methods were compared for 60Co gamma rays, 4-25-MV photons, and 10-25-MeV electrons. Fricke derived doses based on a constant yield (epsilon mG) were in good agreement with ionization derived doses based on the American Association of Physicists in Medicine Task Group 21 protocol and the National Research Council of Canada (NRC) ND calibration or the NRC proposed Nx. These measurements also confirmed the validity of the double voltage technique in the collection efficiency correction, even for swept electron beams. Assuming the correctness of the ionization derived doses, the radiation yield appeared to be 1% higher and to increase with photon energy when irradiation vessels were made of Pyrex but not with polystyrene cells. These glass wall effects could be due to the scattering perturbation of electrons between inhomogeneous materials and, in particular for photon beams, due to the mismatch in mass energy absorption ratios and mass collision stopping power ratios between the Fricke dosimeter and the wall materials. PMID- 2215406 TI - Theoretical and experimental evaluation of a temperature controller for scanned focused ultrasound hyperthermia. AB - Maintenance of the controlled temperatures at their target levels in the face of disturbances, a uniform temperature distribution within the treatment region, an acceptable temperature rise outside that volume, a fast temperature rise, and stability are desirable characteristics of an optimal hyperthermia treatment control system. This paper presents a proportional-integral-derivative plus bang bang (power on at either a maximum value or at zero) feedback control system designed to meet the above requirements for a scanned focused ultrasound hyperthermia system. Treatment stimulations and analytical results for a first order approximation of a tumor show that the controller is stable for a wide range of gains and sampling times. It was also found that there is an optimal controller gain which minimizes the peak temperature overshoot and the settling time when a step function input is applied to the system. Both the simulation results and experimental animal results show that the controlled region can be rapidly heated to the target temperature with a small overshoot and maintained at that level in the face of disturbances. The effects of temperature fluctuations due to both the periodic changes caused by the scanning and due to measurement noise can be reduced by the use of an auto regressive moving average approach. In vitro dog kidney model and in vivo dog thigh experiments show that the controller works well in practice, and verify that it can compensate for spatial and temporal blood perfusion variations. As shown in both these experiments and in simulations the controller can be used for controlling a single temperature or multiple temperature points simultaneously, thus allowing relatively uniform temperature fields to be created. PMID- 2215407 TI - The development of intracavitary ultrasonic applicators for hyperthermia: a design and experimental study. AB - This study investigated the design concepts and development of a multielement intracavitary ultrasound applicator for use in hyperthermia. A necessary condition imposed on these applicators is that each transducer element be separately powered and produce collimated beams. This way, the power deposition within the target volume can be controlled by varying the power to each element. Theoretical computer simulations (acoustic and thermal) and bench experiments were used to determine the constraints on the transducer element size and the spacing between them. These have shown that the length of the cylindrical segments (or subsections of) must be greater than approximately 10 lambda for proper collimation and that the spacing between them must be less than approximately 1.5 mm for uniform heating. With these design principles in mind, applicators were constructed using sections of cylindrical transducers (wall thickness resonance). These were surrounded by temperature-controlled circulating water which was enclosed by a latex membrane. This allowed for acoustic coupling and additional control over the depth of the maximum temperature from the cavity wall. This depth could be varied between the cavity surface and up to 1.5 cm for circulating water temperatures between 5 and 42 degrees C, respectively. These applicators were tested in vivo and were able to induce controlled transrectal heating, at depths of 2-3 cm, in the canine rectum and prostate gland. PMID- 2215408 TI - Surface dose in intracavitary orthovoltage radiotherapy. AB - Radiotherapy with orthovoltage techniques is often the prime treatment for localized superficial malignancies. Surface doses and depth doses measured with cylindrical and end-window Farmer chambers are presented for various orthovoltage x-ray beams in the range from 80 to 300 kVp, both for open beams and beams collimated with commercial intracavitary leaded-glass cones. For radiation fields collimated by a diaphragm positioned at a distance from the patient surface (open beams) there is a small skin-sparing effect. On the other hand, the surface doses with commercial leaded-glass intracavitary cones can exhibit a fivefold increase compared to the open-beam dose maxima. Beyond a depth of approximately 0.2 mm in a tissue-equivalent phantom, the doses measured for open beams and beams collimated with intracavitary cones are essentially identical. The increase in the surface dose observed with intracavitary cones is attributed to photoelectrons and recoil electrons produced in the cones. The high surface doses are measured by thin-wall parallel-plate ionization chambers but cannot be measured with cylindrical Farmer chambers since these chambers have wall thicknesses too large for the transmission of electrons produced in the cone. Since cylindrical Farmer chambers are typically used for calibration of radiation output, the high surface doses produced by the intracavitary cones may be overlooked; they can, however, be reduced to open-beam values by simple modifications to the cones. PMID- 2215409 TI - Dosimetry of Sr-90 ophthalmic applicators. AB - Sr-90 ophthalmic applicators are commonly used for the treatment of superficial eye disorders. Although a variety of dosimetric devices such as film, thermoluminescent dosimeters (TLD's), ion chambers, and radiochromic foils have been used to measure the peak dose at the applicator surface, there is no internationally agreed upon calibration procedure. Recently, large discrepancies among calibrations of the same applicator at three institutions have been reported. Here we describe a technique to obtain the peak dose rate at the applicator surface using LiF TLD's. The technique can be used for the calibration of flat as well as curved surface applicators. Results for two flat and three concave applicators are presented. Our measurement of the surface dose rate for one of the flat applicators is compared with those obtained by four other institutions, each using different dosimetric devices. PMID- 2215410 TI - X-ray spectral reconstruction from attenuation data using neural networks. AB - An artificial neural network using input data derived from attenuation measurements was trained to generate spectral profiles (relative number of photons versus energy). Once the relative spectral distribution is reconstructed, absolute spectra (number of photons per unit exposure spectral distribution is reconstructed, absolute spectra (number of photons per unit exposure versus energy) can be calculated. A neural network was trained on spectra generated mathematically using the Birch-Marshall model, combined with attenuation data, calculated from the spectra by numerical integration. Whereas attenuation data can be calculated in a straightforward manner from the x-ray spectra, the reverse is not true. Several neural networks were successfully taught to reconstruct the spectra, given the attenuation data. The networks were tested using kV/inherent filtration combinations that were not in the training set, and the performance of the reconstruction was excellent. Noise in the attenuation data was simulated to test the effects of noise propagation in the reconstruction. The effects of network architecture and data averaging on noise propagation were investigated. Experimentally determined spectral data complied by Fewell were also used to train a neural network, and the results of the reconstruction were also found to be excellent. PMID- 2215411 TI - Studies of performance of antiscatter grids in digital radiography: effect on signal-to-noise ratio. AB - We developed a theoretical model which describes the improvement of signal-to noise ratio (SNR) by a grid in digital radiography. The model takes into account the effects of spatial variations in the scatter-to-primary ratio and in the large-area contrast over an image with structured background on quantum noise, and the effects of noise in the imaging system such as electronic noise and digitization noise. Based on the theoretical model, we analyzed the effects of these factors on the SNR when a grid is employed. We performed experimental measurements to evaluate the improvement in the SNR by a grid when quantum noise is the dominant noise source. It was found that the measured SNR improvement factor due to quantum noise agreed closely with that determined from the measured transmission values of a grid, as predicted from our theoretical model. In order to evaluate the relative performance of grids with various geometric design parameters for digital radiographic systems, we employed Monte Carlo calculations and determined the transmission values of a number of grids under various scatter conditions. The calculated SNR improvement factor, due to quantum noise, correlated well with the measured improvement of the SNR by the grids. Our model predicts that the SNR improvement factor depends strongly on the local contrast ratio and also on the scatter-to-primary ratio. The SNR improvement factor is higher in the underpenetrated regions than in the well-penetrated regions of an image. PMID- 2215412 TI - Dual-energy mammography: a detector analysis. AB - Dual-energy mammography acquisition scenarios employing single-shot techniques are examined using computer simulation. A figure of merit of the signal-to-noise ratio squared over the glandular dose was chosen for the optimization task due to its exposure independence. Doses were evaluated using Monte Carlo techniques. The effects of kilovoltage, prepatient filtration, front detector thickness, mid detector filtration thickness and composition were studied. Of the six detector pairs studied (Y2O2S/Gd2O2S, SrFBr/BaFBr, Y2O2S/LaOBr, Y2O2S/CaWO4, Y2O2S/YTaO4, and Y2O2S/LuTaO4), Y2O2S/Gd2O2S and SrFBr/BaFBr were found to be the best combinations. The effects of scatter and signal quantization were also examined. An alternative display technique whereby the tissue-subtracted (i.e., calcium) image is colorized and overlaid onto the conventional mammogram is introduced. PMID- 2215413 TI - Logistic representation of the sensitometric response of screen-film systems: empirical validation. AB - An empirical logistic model that linearizes the sensitometric response data of screen-film systems over the entire dynamic range of exposures is presented. This linearization is evident when the net optical densities are scaled as fractions of the net saturation density and plotted on commercial logit, probit, or double log paper, except under conditions of reciprocity law failure. Weighted linear regression analysis shows that the intercept, but not the slope, depends on the screen-film system used. Previous work indicates that the slope is also independent of development time and photon energy. The model is verified through an analysis of tabulated sensitometric data published by the Center for Devices and Radiological Health. PMID- 2215414 TI - Digital TV tomography: description and physical assessment. AB - A digital TV tomography system, capable of retrospective reconstruction of multiple digital tomographic images, has been developed and its basic physical characteristics have been evaluated. The multiple tomographic images were formed through retrospective reconstruction of digital data acquired on a linear tomographic x-ray unit and an image intensifier-television system. Digital data were obtained with a series of 30 pulsed exposures during linear motion of the system. A distortion correction algorithm for the convex surface of the image intensifier was developed in order to reduce image distortion. A phantom study showed that the square-wave response at the fulcrum plane was slightly inferior to that in conventional tomography. There was also a slight decrease in the square-wave response away from the fulcrum plane and upon application of a correction algorithm, as compared with the response of the original reconstructed image at the fulcrum plane. The exposure dose for a single image was approximately half that in conventional tomography. Because of many advantages, including low exposure, short examination time, digital image manipulation, and applicability to picture archiving and communication systems, this is likely to become an important method in radiology when further technical refinements have been made. PMID- 2215415 TI - Harmonic structure of cylindrical imaging coils. AB - Presented is a derivation of an exact closed-form expression for the spectra of resonant frequencies for magnetic resonance imaging birdcage coils in the limit of long coils with many elements. Results of the analysis are compared with observation in a variety of birdcage coils where it is shown that for even relatively short coils the progression of resonant frequencies are of the form omega m = omega 1m +/- 1/2 + low pass; -high pass, with m integer and omega 1 the primary resonance. PMID- 2215416 TI - Problems associated with simulated light sensitometry for low-crossover medical x ray films. AB - Over the past ten years the evolution of medical x-ray films has been toward films with reduced intensifying-screen light crossover in order to reduce blur and obtain higher spatial resolution. For films with very low crossover, misleading and incorrect sensitometric data may be obtained for film contrast evaluation and processor control if a simulated light sensitometer with a single sided, light-exposing device is used. Screen light exposures were made using an inverse square, intensity-scale sensitometer. Simulated light exposures were made using a widely used single-sided, simulated-light sensitometer commonly used for film processor quality control, and a new simulated-light sensitometer capable of producing either single- or double-sided sensitometric exposures. The films used included one single-emulsion film and three double-emulsion medical x-ray films with light-crossover values ranging from approximately 3% to 30%. Sensitometric data showed a significant distortion (bump) in the characteristic curve for the 3% light-crossover film exposed with the single-sided, simulated-light sensitometer. PMID- 2215417 TI - Light equalization radiography. AB - An electro-optical, photographic dodging technique, called light equalization radiography (LER), has been developed. The use of LER extends the dynamic range of radiographic film by enhancing the film contrast in the "toe" region of a radiographic film. Contrast recorded above some predetermined optical density is unaffected. The use of LER permits high-contrast films to be used in radiographic exams where low-contrast, "latitude" film types have been used traditionally, e.g., in chest radiography. PMID- 2215418 TI - Evaluation of captive bolus applicators. AB - Three square (L, M, MS) and one rectangular (HN) applicators with captive boluses were provided by the Clini-Therm Corporation for evaluation. Surface cooling is achieved by attaching a mineral oil captive bolus to the built in water circulating tubes at the aperture of the applicators. These applicators were tested on a phantom with a 2-cm fat slab over 10-cm-thick muscle. Surface and sagittal heating patterns were obtained using a thermograph. All captive-bolus applicators have heating patterns similar to that of the regular Clini-Therm applicators. Due to hot spots at the edges of the applicators where the E fields terminate, these modified applicators should not be placed in direct contact with patients when boluses are not used. Tests with Clini-Therm regular water bolus instead of the captive oil bolus indicated that the orientation of water flow should be parallel to the E field to minimize perturbation of the heating patterns. Thermal conduction studies showed that the captive bolus reacts too slowly for skin temperature control. The modified captive bolus applicators did not improve the performance of the system. PMID- 2215419 TI - Radiation leakage through electron applicators on Clinac-1800 accelerators. AB - Radiation leakage through electron applicators by 6-, 9-, 12-, 16-, and 20-MeV electron beams from Varian Clinac-1800 has been measured with films. High levels of leakage were found under the corners of applicators and the touch-plate mounting port holes. The radiation leakage, relative to the central-axis dose at dmax, was found to be up to 13% on the patient plane [100-cm source-to-film distance (SFD)] and up to 35% beneath the corners of applicators (96-cm SFD). Up to 18% radiation leakage was measured beneath the touch plate near the mounting port holes (96-cm SFD). The extent of radiation leakage in all electron beams was investigated and some simple shielding solutions to reduce the leakage are suggested. PMID- 2215420 TI - PET genes of Saccharomyces cerevisiae. AB - We describe a collection of nuclear respiratory-defective mutants (pet mutants) of Saccharomyces cerevisiae consisting of 215 complementation groups. This set of mutants probably represents a substantial fraction of the total genetic information of the nucleus required for the maintenance of functional mitochondria in S. cerevisiae. The biochemical lesions of mutants in approximately 50 complementation groups have been related to single enzymes or biosynthetic pathways, and the corresponding wild-type genes have been cloned and their structures have been determined. The genes defined by an additional 20 complementation groups were identified by allelism tests with mutants characterized in other laboratories. Mutants representative of the remaining complementation groups have been assigned to one of the following five phenotypic classes: (i) deficiency in cytochrome oxidase, (ii) deficiency in coenzyme QH2 cytochrome c reductase, (iii) deficiency in mitochondrial ATPase, (iv) absence of mitochondrial protein synthesis, and (v) normal composition of respiratory-chain complexes and of oligomycin-sensitive ATPase. In addition to the genes identified through biochemical and genetic analyses of the pet mutants, we have cataloged PET genes not matched to complementation groups in the mutant collection and other genes whose products function in the mitochondria but are not necessary for respiration. Together, this information provides an up-to-date list of the known genes coding for mitochondrial constituents and for proteins whose expression is vital for the respiratory competence of S. cerevisiae. PMID- 2215421 TI - Genetics of Candida albicans. AB - Candida albicans is among the most common fungal pathogens. Infections caused by C. albicans and other Candida species can be life threatening in individuals with impaired immune function. Genetic analysis of C. albicans pathogenesis is complicated by the diploid nature of the species and the absence of a known sexual cycle. Through a combination of parasexual techniques and molecular approaches, an effective genetic system has been developed. The close relationship of C. albicans to the more extensively studied Saccharomyces cerevisiae has been of great utility in the isolation of Candida genes and development of the C. albicans DNA transformation system. Molecular methods have been used for clarification of taxonomic relationships and more precise epidemiologic investigations. Analysis of the physical and genetic maps of C. albicans and the closely related Candida stellatoidea has provided much information on the highly fluid nature of the Candida genome. The genetic system is seeing increased application to biological questions such as drug resistance, virulence determinants, and the phenomenon of phenotypic variation. Although most molecular analysis to data has been with C. albicans, the same methodologies are proving highly effective with other Candida species. PMID- 2215423 TI - Microbial degradation of hydrocarbons in the environment. AB - The ecology of hydrocarbon degradation by microbial populations in the natural environment is reviewed, emphasizing the physical, chemical, and biological factors that contribute to the biodegradation of petroleum and individual hydrocarbons. Rates of biodegradation depend greatly on the composition, state, and concentration of the oil or hydrocarbons, with dispersion and emulsification enhancing rates in aquatic systems and absorption by soil particulates being the key feature of terrestrial ecosystems. Temperature and oxygen and nutrient concentrations are important variables in both types of environments. Salinity and pressure may also affect biodegradation rates in some aquatic environments, and moisture and pH may limit biodegradation in soils. Hydrocarbons are degraded primarily by bacteria and fungi. Adaptation by prior exposure of microbial communities to hydrocarbons increases hydrocarbon degradation rates. Adaptation is brought about by selective enrichment of hydrocarbon-utilizing microorganisms and amplification of the pool of hydrocarbon-catabolizing genes. The latter phenomenon can now be monitored through the use of DNA probes. Increases in plasmid frequency may also be associated with genetic adaptation. Seeding to accelerate rates of biodegradation has been shown to be effective in some cases, particularly when used under controlled conditions, such as in fermentors or chemostats. PMID- 2215425 TI - The quality of the last year of life of older persons. AB - Researchers have begun devising measures of the quality of the entire last year of life of older community residents. Investigators in Philadelphia surveyed 150 living elderly on features of their quality of life, and matched the responses with 200 retrospective estimates obtained from relatives of decedents who had resided in the community much of the year. Most indicators showed declines for the decreased over their final year when compared with persons still alive; 82 percent of the decedents, however, experienced a majority of "positive-quality" months in their last year. Debates on the costs and ethical aspects of treatment and care need to take account of "positive" and "negative" aspects of quality of life reflecting individuals' multifaceted existence. PMID- 2215426 TI - Medicaid in the inner city: the case of maternity care in Chicago. AB - The growing concentration of lower-income groups, including Medicaid patients, in homogeneous inner-city areas such as Chicago casts considerable doubt on the effectiveness of expanding Medicaid eligibility and raising physician reimbursement to improve access to maternity care. There are few private office based physicians providing prenatal care in these areas, and most pregnant women and infants are treated by private-office-based physicians in very high-volume practices, prompting concern about the quality of care. Increasing the supply of providers is required to enhance access to maternity services in inner cities. Expanding eligibility and raising reimbursement rates are more apt to benefit "near-poor" women, who are more spatially dispersed, than clustered-poor female populations. PMID- 2215422 TI - The fungal vacuole: composition, function, and biogenesis. AB - The fungal vacuole is an extremely complex organelle that is involved in a wide variety of functions. The vacuole not only carries out degradative processes, the role most often ascribed to it, but also is the primary storage site for certain small molecules and biosynthetic precursors such as basic amino acids and polyphosphate, plays a role in osmoregulation, and is involved in the precise homeostatic regulation of cytosolic ion and basic amino acid concentration and intracellular pH. These many functions necessitate an intricate interaction between the vacuole and the rest of the cell; the vacuole is part of both the secretory and endocytic pathways and is also directly accessible from the cytosol. Because of the various roles and properties of the vacuole, it has been possible to isolate mutants which are defective in various vacuolar functions including the storage and uptake of metabolites, regulation of pH, sorting and processing of vacuolar proteins, and vacuole biogenesis. These mutants show a remarkable degree of genetic overlap, suggesting that these functions are not individual, discrete properties of the vacuole but, rather, are closely interrelated. PMID- 2215427 TI - Choices in prescription-drug benefit programs: mail versus community pharmacy services. AB - Pharmaceutical price increases and greater coverage of outpatient prescription medications have stimulated interest in containing drug benefit-program costs. While mail pharmacy services (MPS) may achieve savings through volume purchasing, high usage of generic drugs, and dispensing larger quantities of medication per prescription, efforts are also underway to adapt community-pharmacy-based services to keep costs down in these areas. No controlled studies document a difference in quality between the two types of services. Third-party administrators and benefit managers need to consider factors such as providing information to patients, monitoring drug therapy, dispensing patients' correct medication, and cost-control incentives when assessing MPS's role in prescription drug programs. PMID- 2215428 TI - 5th European Congress of Clinical Neurophysiology. Paris, 9-12 September 1990. Abstracts. PMID- 2215429 TI - Nursing in the 1990s--developing policies for nurse education. PMID- 2215430 TI - Nurse Education Tomorrow Conference theme paper--section A. The path to nursing knowledge--personal reflections. AB - The author provides a definition of nursing knowledge, reviews the critical literature up to 1989 and discusses the current trends. She concludes her paper with her reflections upon the path to true nursing knowledge. PMID- 2215424 TI - Parvovirus replication. AB - The members of the family Parvoviridae are among the smallest of the DNA viruses, with a linear single-stranded genome of about 5 kilobases. Currently the family is divided into three genera, two of which contain viruses of vertebrates and a third containing insect viruses. This review concentrates on the vertebrate viruses, with emphasis on recent advances in our insights into the molecular biology of viral replication. Traditionally the vertebrate viruses have been distinguished by the presence or absence of a requirement for a coinfection with a helper virus before productive infection can occur, hence the notion that the dependoviruses (adeno-associated viruses [AAV]) are defective. Recent data would suggest that not only is there a great deal of structural and genetic organizational similarity between the two types of vertebrate viruses, but also there is significant similarity in the molecular biology of productive replication. What differs is the physiological condition of the host cell that renders it permissive. Healthy dividing cells are permissive for productive replication by autonomous parvoviruses; such cells result in latent infection by dependoviruses. For a cell to become permissive for productive AAV replication, it must have been exposed to toxic conditions which activate a latent AAV genome. Such conditions can be caused by helper-virus infection or exposure to physical (UV light) or chemical (some carcinogens) agents. In this paper the molecular biology of replication is reviewed, with special emphasis on the role of the host and the consequences of viral infection for the host. PMID- 2215431 TI - A review of two theories of learning and their application in the practice of nurse education. AB - From the range of learning theories which may be applied in the practice of nurse education, two contrasting theories have been selected. The 'conditions of learning and theory of instruction' (Gagne, 1985) derives from the behaviourist perspective in psychology, and Rogers' (1983) description of learning has evolved from the Humanistic School. This discussion initially focuses on Gagne's work beginning with a review of his 'conditions of learning', and is followed by a consideration of Rogers' approach through the 'facilitation of learning' (Rogers, 1983). The respective strengths and limitations of the two theories as applied in nurse education are then compared. PMID- 2215432 TI - The conceptual basis of mental health nursing. AB - This paper traces the historical roots of mental health nursing relating these to contemporary practice in the case of people with all forms of mental illness. An attempt is made to explain the current interest in the nurse's interpersonal role with reference to specific theoreticals models and the development of care practices which emphasise social systems or social relationships. Emphasis is given to reports in the British literature, although some reference is made to North American nursing commentators. It is argued that although research evidence is weak, strong indications exist to suggest that the nurse's primary role lies in the imagination of their interpersonal relationship with the patient in an attempt to effect lasting change in the patient's capacity to live an ordinary life. PMID- 2215433 TI - Nurse Education Tomorrow Conference theme paper--section D. The student experience: adult learning and mentorship revisited. AB - Nursing education is being cited frequently as an example of adult education. Mentorship is also a concept that has been adopted as an approach to enhancing learning in the clinical setting. This paper examines, critically, the notions of adult learning, andragogy and mentorship and explores their relationship to modern nursing educational practice. PMID- 2215434 TI - An innovation in a diploma program: the future potential of mentorship in nursing. AB - This paper reports on the processes used to facilitate the implementation of a mentored elective placement for final year nursing students and the results of the evaluative phase of this innovation. The mentors were experienced clinical practitioners who formed mentored relationships with final year students in a selected area of nursing practice and had been prepared for their role by a program organized and conducted by the Faculty. The evaluation phase incorporated the multi-method approach of triangulation to gather data during the implementation phase of the mentored placement. The results tend to be strongly supportive of a continuation of this innovation and were based on data gathered from both the mentor and mentee perspectives. The final evaluation tool aimed to assist in clarifying the role of the mentor and was administered to the mentees at the completion of the placement. Factor analyses of the mentees' responses generated four underlying constructs to mentorship, namely, the quality of the relationship, professional role acquisition, socialisation into the work role, and a need to promote mentor relationships in nursing. PMID- 2215435 TI - Change in nursing and the introduction of the support worker. AB - Many changes have occurred in the British nursing profession over the last 15 years, including the introduction of the nursing process, the change in emphasis to holistic care, the contemporary focus on wellness rather than illness, models of nursing, primary nursing and Project 2000. These changes are discussed as the outcome of the interaction between groups of nurses of various ideological persuasions. Firstly, the ideologies of professionalism, bureaucracy and paramedicine are identified and described. Next, the historical relationship between these ideological groups is discussed. The paramedical ideology, as an expression within nursing of the controlling power of the medical profession, dominated nursing for many years. Its position was maintained through means that included the division of labour (as seen in task allocation) and the control of knowledge (as seen in a medically modelled nursing curriculum). More recently, however, the professionalists have gained the upper hand. In the paper, each of the changes identified above is seen as part of a strategy of professionalisation. The main thrust of this strategy has been to reunite the divided nursing function, and to redefine the nature of nursing knowledge through the development of nursing theory. The introduction of the support worker grade is an attempt to consolidate professionalist control by re-dividing nursing labour between the stages of the nursing process, with professional nurses being responsible for care planning, while support workers undertake its delivery. The professionalists can now be described as an occupational hegemony. PMID- 2215436 TI - The perceptions of students and teachers regarding the introductory module of an enrolled nurse conversion course. AB - This study sets out to explore the perceptions of students' and their teachers' regarding the Introductory Module of a course to convert Enrolled Nurses to Registered General Nurses. The course has been developed as a joint venture with two local Schools of Nursing as an experiment in joint course management. An illuminative evaluation approach has been adopted utilising the techniques of observation, questionnaires and interviews, in order to provide information by a variety of means upon which the course management team can base their future decisions regarding the course. The findings suggest that the introductory module was perceived by the students and teachers as a valuable learning experience. Issues specific to the course which were highlighted included the need for the involvement of the course teachers from each School of Nursing in the teaching programme, the introduction of negotiated student learning, a joint approach to the assessment of theory and practice and a modification of the maternity and community care experience. General issues related to the students as mature learners included the need for pre-course preparation for the students, the assessment of individual learning needs, the inclusion in the content of essay writing skills and stress management and the need for a comprehensive staff development programme for the teaching staff. The study highlighted the need for evaluation of nurse education programmes and teaching methods in order to provide professional accountability and to ensure nurse education practice is research based. PMID- 2215438 TI - From Project 2000 to diploma of higher education curriculum and course development. PMID- 2215437 TI - Nurse education initiatives--making Project 2000 a reality. Managing the dynamic organisation. PMID- 2215439 TI - Project 2000: the higher education context. PMID- 2215440 TI - District general manager's perspective. PMID- 2215441 TI - Prenatal diagnosis and congenital disease: role of the clinical nurse specialist. AB - Birth defects reflect the infant's genetic constitution and are generally divided into four major categories: multifactorial, single-gene, chromosomal, and environmental. The etiology of the specific disorder is directly related to its risk of occurrence/recurrence, which can be theoretically or specifically calculated. Suspicion of genetic disease in an unborn child is heightened by a history of disease in blood relatives and by the presence of multiple miscarriages and/or increased maternal age. Current prenatal screening tools include maternal/fetal sampling (tissue, cells, amniotic fluid) and fetal visualization. All these tests have specific complications and limitations. Families undergoing prenatal testing are likely to experience anxiety, which may continue throughout the pregnancy despite a diagnosis of an unaffected fetus. Such anxiety can interfere with attachment to the unborn child. The aware clinical nurse specialist is in a position to help all parents by providing clear and accurate information, sensitive emotional support, and by optimizing social support systems. PMID- 2215442 TI - Minimal handling protocol for the intensive care nursery. AB - Use of a conceptual model of nursing for the minimal handling protocol provides organization and a theoretical basis for nursing care standards. Levine's principles of conservation of energy, structural integrity, personal integrity, and social integrity provide a concrete approach for making nursing care judgments. Through individualized adaptation and implementation of the minimal handling protocol, neonatal intensive care nurses will be able to deliver high quality therapeutic and supportive care in the least stressful and most protective manner possible to high-risk infants. PMID- 2215443 TI - How reliable are scales for weighing preterm infants? PMID- 2215444 TI - Early experience with the neonatal resuscitation program. PMID- 2215445 TI - Childbearing and childrearing practices in Mormonism. PMID- 2215446 TI - Standardized care plan: extracorporeal membrane oxygenation. PMID- 2215447 TI - Perspectives on newborn male circumcision. AB - Routine newborn circumcision cannot be widely advocated until large prospective studies thoroughly document its prophylactic value. When circumcision is performed properly, it represents a low-risk surgical procedure. The nursing profession plays a pivotal role in counseling and educating parents. A nurse can adeptly intervene in the psychosocial dynamics of the family to facilitate a truly informed parental decision. PMID- 2215448 TI - Neonatal Bill of Rights. PMID- 2215449 TI - Applying the decision-making model: case study 1. AB - The options for decision making in this situation are reviewed in step 8. As you select one of these options or add one not listed, ask yourself the following questions: Why did I select that particular option? Is this option I selected consonant with my own personal and professional values? If not, where are the conflicts? Have I considered all the evidence in a logical sequence, or did I jump to my conclusion when I first read through the case? Have I had experience caring for a mother and infant in a similar situation? If so, to what extent did my previous experience influence my choice of action in this situation? Can I implement the decision? If not, why? This series of questions can assist the nurse or other health professional in actually making a decision and thinking about their personal reaction to implementing it (accountability). Critical thinking and taking time to analyze one's decision-making process are important tools that help each of us make morally appropriate decisions in clinical practice. The results are better patient care and the personal satisfaction of knowing you have done your best to promote the best interests of infants assigned to your care. PMID- 2215450 TI - Surfactant replacement therapy: a second look. PMID- 2215451 TI - The not-so-ancient history of neonatal research. PMID- 2215452 TI - Fentanyl citrate. PMID- 2215453 TI - Pediatric neurology. PMID- 2215454 TI - Peroxisomal disorders. AB - Although peroxisomes were once considered a vestige, their importance in cellular metabolism is clearly established by the many inherited diseases that have been described in the past two decades. Unfortunately there is no definitive treatment for the various disorders, but based on the recognition of the biochemical abnormalities, prenatal testing and appropriate genetic counseling can be provided. It is essential for clinicians to be aware of this group of diseases, as diagnosis and further study of these patients are essential in understanding the basic etiologic mechanisms underlying these complex groups of disorders. Clearly, there is much to be learned about the relationship between biochemical abnormalities and the phenotypic variability of the peroxisomal disorders. PMID- 2215455 TI - The IVH complex of lesions: cerebrovascular injury in the preterm infant. AB - The term intraventricular hemorrhage has become associated with a variety of cerebrovascular insults in preterm infants. Because of a shared pathophysiology and timing, these are the neurologic lesions to search for when evaluating sick preterm infants. This complex of lesions is common and, when parenchymal injury occurs, likely to result in neurologic sequelae. A review of the variety of injuries, their pathophysiology, their diagnosis by cranial ultrasonography, and their prognosis is offered. Emphasis is placed on the need for assessment over time when evaluating parenchymal lesions in preterm infants. PMID- 2215456 TI - The molecular biology of occlusive stroke in childhood. AB - It is very likely that many of the same factors involved in occlusive disease in the adult are operative in the child. The major difference may be in the factors that damage endothelium in these two age groups and thereby initiate this catastrophe (atherosclerosis versus "other" causes of endothelial changes). Our task in this next decade is the rational exploration of the effects of endothelium-mediated kinins, endothelial secretory products, angiospasm, platelet aggregration, prostaglandins, and lipoproteins on pediatric stroke. PMID- 2215457 TI - AIDS and pediatric neurology. AB - Human immunodeficiency virus type 1 (HIV-1), the etiologic agent of AIDS, causes a wide spectrum of disease in children owing to its selective tropism for the immune system, nervous system, and perhaps other organs. By 1991, there may be as many as 10,000 to 15,000 children with symptomatic HIV-1 infection in the United States. This article reviews the current knowledge of the clinical, neuroradiologic, and neuropathologic features of HIV-1-related central nervous system involvement in infants and children with symptomatic HIV infection. PMID- 2215458 TI - Bacterial meningitis: an update. AB - Antibiotics and improvements in supportive care have greatly reduced the mortality from bacterial meningitis. Nevertheless, the incidence of neurodevelopmental sequelae remains unacceptably high. Ampicillin and chloramphenicol remain the standard for antimicrobial therapy against which other agents must be compared. A number of adjunct therapies are being investigated for their possible effectiveness in reducing hearing loss and other neurologic effects of this disease. There continues to be a need for carefully performed follow-up studies to assess any possible benefit of these agents. A significant percentage of children surviving an episode of bacterial meningitis have obvious or subtle neurodevelopmental deficits. The role of the pediatric neurologist should not end with management of acute problems such as seizures but should be expanded to aid in close developmental monitoring of these high-risk children. PMID- 2215459 TI - The classification of childhood seizures and epilepsy syndromes. AB - The classification of seizures and the epileptic syndromes is particularly relevant to those who treat children, as most syndromes are age related, with onset between the neonatal and adolescent periods. Whereas seizures are characterized by ictal behavior and EEG findings, epilepsy syndromes are defined by seizure type, etiology, age of onset, natural history, possible genetic factors, and prognosis. Limitations exist, but attempts to use these classifications typically lead to a better understanding of the patient and allow for more precise evaluation and treatment. PMID- 2215460 TI - Infantile spasms. AB - Infantile spasms are a seizure disorder in young infants with diverse etiologies, suggesting that they arise from any disturbance of central nervous system function during susceptible periods of development. The prognosis for normal intellectual and neurologic development parallels that of the underlying etiology. Early and appropriate treatment with ACTH may lead to seizure control in a majority of patients. The treating physician must anticipate the side effects of this modality. PMID- 2215461 TI - Status epilepticus in infancy and childhood. AB - Status epilepticus implies a prolonged seizure or recurrent seizures with persistent decreased consciousness, lasting at least 30 minutes. Both convulsive and nonconvulsive forms exist, either of which may lead to death or additional neurologic deficit. Therapy involves careful supportive care plus some combination of benzodiazepines, phenytoin, or phenobarbital. The outcome depends first on the etiology and second on the rapidity with which seizures are controlled. PMID- 2215462 TI - Rett syndrome and the autistic disorders. AB - Rett syndrome is a disorder noted to date only in females and characterized by a pervasive developmental disability following apparently normal early infancy. In addition to gait difficulties, stereotypic hand movements, and loss of communication and purposeful hand skills, autistic-like behavior is an early sign that often results in misdiagnosis. Despite these significant clinical abnormalities, neuropathologic features are modest, and no consistent laboratory abnormality or diagnostic marker has been identified. The current status of research in RS is considered within the context of autism and other disorders in which autistic features may occur, such as the fragile X syndrome. The concept of autism as neurobiologically based behavior is developed. As such, autism is regarded as an umbrella category containing an ever-expanding list of specific disorders. PMID- 2215463 TI - Pediatric behavioral neurology: an update on the neurologic aspects of depression, hyperactivity, and learning disabilities. AB - The high incidence of poor social adjustment in long-term follow-up studies of depressed children seems to relate to the inadequacy of the pharmacotherapy necessary to sustain long-lasting remission or possibly to repetitive inappropriate stresses. Insufficient antidepressant therapy with resultant intermittent depression-induced dysfunction of the socialization functions performed by the right cerebral hemisphere would not permit the child to develop appropriate interpersonal skills (causing failure in most social situations), and associated cognitive difficulties would complicate academic performance. Repeated school failure and chronic social ineptitude preclude development of the skills necessary for successful independent living in society. Thus, if symptoms of depression are found, it is imperative that the learning-disabled or behaviorally disturbed child or adolescent receive adequate antidepressant therapy to ensure complete long-term remission of the depression. In addition, learning-disabled individuals, even without apparent diagnosable depressive illness, must be offered appropriate methods for learning and communication which reduce stress. When such appropriate educational strategies are offered and poor performance still ensues (or continues), a trial of antidepressant therapy should be considered. Recognition of the depressive nature of symptoms may not be possible until treatment-induced improvement has occurred and depression-associated learning disability has resolved. Improvement in academic performance associated with improved cognitive function after treatment-induced remission of a depressive episode can be dramatic, with resolution of apparent learning disability. Poor educational achievement associated with chronic learning difficulties ultimately affects adult social functioning, and untreated or improperly treated chronic depression may result in the development of later personality disturbances. Therefore, before attributing school problems in children to untreatable conditions, depressive disorder must be excluded, and appropriate antidepressant therapy (along with removal of all apparent inappropriate stress, including inappropriate demands on brain function) should be provided to children and adolescents with evidence of depression. PMID- 2215464 TI - Tourette syndrome: recent advances. AB - Clinical and genetic studies have allowed the limits of Tourette syndrome to be broadened. There is now strong evidence that chronic motor tics and Tourette syndrome are different manifestations of an autosomal dominant gene with high penetrance. A genetic link with obsessive-compulsive disorder also appears to have been established. Up to 10% of cases of Tourette syndrome may be nongenetic phenocopies, however. There is also an association between Tourette syndrome and attention deficit hyperactivity disorder. This complicates therapy, as psychostimulant drugs may precipitate or exacerbate tics in some individuals. A high proportion of patients with Tourette syndrome also has neuropsychological deficits and learning disabilities. The pathophysiology is incompletely understood. The best supported hypothesis is that there is dopamine receptor supersensitivity, although there are strong suggestions of abnormalities in serotonin metabolism. The possibility of abnormalities in neuropeptide systems is being explored. Treatment of tics relies primarily on neuroleptics with dopamine receptor blocking activity. Clonidine may be useful in some patients, especially those with behavior problems. Obsessive-compulsive symptoms can be treated using appropriate pharmacologic agents. The treatment of attention deficit disorder in patients with tics should begin with behavioral strategies. Clonidine can be tried as the first-line drug, and psychostimulants should be used only if necessary and with great caution. In rare instances it may be necessary to combine a psychostimulant and a neuroleptic. PMID- 2215465 TI - The floppy infant: recent advances in the understanding of disorders affecting the neuromuscular junction. AB - The clinician is often asked to evaluate the floppy infant. Numerous conditions that cause hypotonia in infancy are briefly outlined in this article. These conditions may affect the brain, spinal cord, or motor unit. Several disorders of neuromuscular transmission, including four distinct and recently described congenital myasthenic syndromes and infant botulism, are discussed thereafter. PMID- 2215466 TI - Magnetic resonance in pediatric and adolescent neuroimaging. AB - With improved availability and a practical understanding of the principles of utilization, MRI will continue to replace CT and US in pediatric neuroimaging, just as it has impacted upon the more invasive modalities. In general, US remains the procedure of choice for screening of fetal and infant CNS abnormalities, and CT continues as the principal screening modality beyond infancy and especially for acute, emergent presentations. MRI has now emerged as a primary option for screening as well as for more definitive assessment of many intracranial and most intraspinal conditions. PMID- 2215467 TI - The use of ultrasound in evaluating neurologic diseases of childhood. AB - Real-time cranial sonography, intracranial Doppler, and neuromuscular sonography are the sonographic techniques that are applicable to the neurologic evaluation of infants and children. Although limited by age, specificity, and operator skill and experience, the advantages of real-time cranial and intracranial Doppler sonography make them useful techniques in the evaluation of the young infant, particularly in the serial assessment of ventricular size and in the study of the critically ill infant. The use of neuromuscular sonography in the assessment of the floppy infant and in the guidance of biopsy makes this an increasingly valuable tool. PMID- 2215468 TI - Refusing life-sustaining medical treatment. PMID- 2215469 TI - Cancer and the ozone hole. PMID- 2215470 TI - Immunization. AB - Scheduled immunization is one of the most important ways that individuals can protect themselves and their children from preventable communicable disease. Through diligent public health efforts, diseases that were once considered common have been mostly eradicated, sparing millions from not only the disease themselves, but their potentially devastating after-effects. PMID- 2215471 TI - Efforts in primary-care practice to control tobacco use. AB - In this article, the authors findings lead them to conclude that because of the devastating effects of smoking on health, the public could experience widespread health benefits if primary care physicians became more active in encouraging patients to stop smoking. PMID- 2215473 TI - Age at death: a three hospital urban, suburban, and small town study. AB - Comparison of the ages of patients dying at three interrelated St. Louis hospitals in 1988 has been used to study the results of similar high-quality acute hospital care when provided to dissimilar populations. The data presented by the authors leads them to conclude that in this era of mounting health costs, we have not, at least as recently as 1988, realized that an ounce of prevention if worth a pound of cure. PMID- 2215472 TI - Current management of primary breast cancer. Part I: Screening, diagnosis, staging and local treatment of stage I and II disease. AB - In the first of two parts, the authors present an overview of screening, staging, diagnosis, and treatment of primary breast cancer. In next month's issue, the aspects of adjuvant therapy, treatment of locally advanced breast cancer, and management of carcinoma in situ will be presented. PMID- 2215474 TI - Educating Missouri health professionals about HIV/AIDS: the Missouri MATEC Program. PMID- 2215475 TI - Public health burden of vaccine-preventable diseases among adults: standards for adult immunization practice. PMID- 2215476 TI - Resistance to the pore-forming protein of cytotoxic T cells: comparison of target cell membrane rigidity. AB - Cytotoxic T lymphocytes (CTL) release from their granules a 70 kDa protein, called PFP, perforin or cytolysin, which inserts into the target cell plasma membrane in its monomeric form. Here it polymerizes into a macromolecular complex forming pores as large as 20 nm. Although purified PFP/perforin can effectively lyze all target cells tested. CTL are refractory to lysis. The mechanism underlying the resistance of CTL is currently unknown. This study represents a search for membrane structural properties that could confer resistance to CTL against PFP/perforin-mediated lysis. The fluorescent dye merocyanine 540 was used to measure the lipid head group packing of CTL and several target cells, and 1-[4 (trimethylamine)phenyl]-6-phenylhexa-1,3,5-triene was used to estimate the fluidity of the membrane hydrocarbon region. The resistance against PFP/perforin mediated lysis was determined by the 51Cr release assay. A comparison of the membrane rigidity with cell resistance led to the conclusion that the membrane lipid structure cannot account for the unusually high resistance of CTL. In particular, the resistant CTL line CTLL-2 has a lipid head group packing that is looser than that of Yac-1, and the sensitive target cells Jy-25 and EL-4 have membrane acyl chains that are less fluid than those of the effector CTLL-R8. PMID- 2215477 TI - The importance of electrostatic interactions in the binding of paraquat to its elicited monoclonal antibody. AB - In this study the pH-dependent interactions interactions between a paraquat specific murine monoclonal antibody and two antigens: paraquat (1,1'-dimethyl 4,4'-bipyridinium dichloride), and a p-nitrophenol analogue (1-(N-methyl-4,4' bipyridinium)-1-(2-hydroxy-5-nitrophenyl)methane dichloride; PQNP) were determined by ELISA. In each case the KAS-pH profile reflected the titration of a single amino acid residue. pK'a values derived from these plots were 8.90 (paraquat) and 8.13 (PQNP). Increasing pH led to a significant increase in the association constant for each antibody complex. A spectrophotometric titration of PQNP in the presence and absence of excess antibody indicated the presence of another charged amino acid residue at the binding site, which could be assigned as a carboxylic acid. From these studies, a model for paraquat-antibody binding has been proposed. PMID- 2215478 TI - The molecular basis of IgE antibody binding to thiopentone. Binding of IgE from thiopentone-allergic and non-allergic subjects. AB - Thiopentone-specific IgE antibodies from the sera of subjects who experienced a life-threatening anaphylactic reaction to the drug and IgE antibodies that cross react with thiopentone via substituted ammonium groups in either cyclic or acyclic form, were studied by direct binding immunoassays and quantitative hapten inhibition methods. Findings provided an explanation for the apparent 'non specific' nature of some IgE antibody reactions with thiopentone and reinforce the conclusion that the thiopentone IgE immunoassay is a valuable aid in the diagnosis of immediate allergic reactions to the drug. PMID- 2215479 TI - Rat polymeric IgA binds C1q, but does not activate C1. AB - Immune complexes, prepared with monoclonal rat IgA antibodies directed against DNP, activate the alternative pathway of the complement system in rat serum. In this study, the interaction of these monoclonal IgA antibodies with the classical pathway of complement was investigated. Monoclonal polymeric IgA (p-IgA) was shown to inhibit the IgG2b-mediated classical pathway-dependent lysis of TNP coated sheep red blood cells. In addition, the binding of C3 to solid phase IgG2b immune complexes was inhibited by p-IgA. Monoclonal monomeric IgA (m-IgA) was much less efficient in this respect. To further analyse the effect of p-IgA on the activation of the classical pathway by IgG2b immune complexes, the interaction of p-IgA with C1 was studied. It was found that p-IgA antibodies bind C1q. No species-specificity was observed, since both rat and human C1q were bound. Whereas binding of C1q in C1 to IgG2b resulted in activation of C1, binding to p-IgA did not. The binding of C1q to both p-IgA and IgG2b could be inhibited by monoclonal antibodies directed against the globular heads of C1q, but not by monoclonal antibodies directed against the collagen tail. The formation of insoluble p-IgA immune complexes was inhibited in the presence of rat serum or C1. These studies indicate that C1q binds to p-IgA by its globular heads, and thereby may modulate classical pathway-mediated reactions such as the inhibition of immune precipitate formation. PMID- 2215480 TI - Structural comparison of murine T-cell (B151K12)-derived T-cell-replacing factor (IL-5) with rIL-5: dimer formation is essential for the expression of biological activity. AB - T-cell-replacing factor (TRF)/IL-5 is a T-cell-derived glycoprotein which has pleiotropic activity on lymphoid and myeloid cells. IL-5 polypeptide translated into Xenopus oocytes are heterogeneous in molecular size (40,000 to 60,000 under nonreducing conditions) and yields a monomeric form (Mr of 25,000 to 30,000) under reducing conditions (J. Immun., 140, 1175-1181, 1988). We purified T-cell derived TRF and rIL-5 using anti-TRF/IL-5 antibody-coupled affinity column from supernatants of a T-cell hybridoma B151K12 and supernatants of HeLa cells, respectively, which had been transfected with murine IL-5 cDNA, and determined their partial N-terminal amino acid sequence (27 residues for B151-TRF and 13 residues for rIL-5). A single amino acid sequence of each sample obtained beginning from methionine that was identical to that predicted from IL-5 cDNA. This finding supports the notion that secreted B151-TRF polypeptide consists of 113 amino acids. Purified B151-TRF supported eosinophilopoiesis of human bone marrow cells as effective as mouse rIL-5 and human rIL-5. B151-TRF competitively inhibited 35S-labeled rIL-5 binding to target cells to the same extent at rIL-5. Treatment of purified rIL-5 and B151-TRF with reducing reagents such as 2-ME, sodium borohydride or dithiothreitol produced a monomeric form of IL-5 which did not exert a biological activity. Reduction and alkylation of rIL-5 caused the loss of binding to its target cells. These results strongly suggest that B151-TRF exists as a homodimer and its primary structure and secondary structures are identical to those of rIL-5. Moreover, the formation of inter-molecular disulfide bond(s) linked by two pairs of cystein residues is essential for the expression of the biological activity of mouse IL-5. PMID- 2215482 TI - [Electrognathographic imaging of the articular click]. AB - The study of TMJ phisiopathology by means of computerizing devices is necessary in order to make a correct diagnosis and verify the therapeutic programme. In this study the Authors analyse articular click that is one of the first and characteristic symptom of the internal derangement. The Authors show by means of elettrognatography, chewing cicles and mandibular border movements of patients affected with this particular pathology. Trascing of 135 patients suffering from tmj reciprocal click have been examined in the department of maxillary-facial of Roma "La Sapienza", surgery during the period 1987-88. PMID- 2215483 TI - [Mandibular laterodeviation of surgical significance]. AB - The Authors look at the mandibular laterodeviations and their classification. They speak about the combined surgical-orthodontic treatment of this pathology and show some clinical cases from their clinical experience. PMID- 2215481 TI - [Functional anterior limits of the dentition]. AB - The Authors propose a further evaluation, during diagnosis which can allow us to label the subject not only from static point of view but also from the functional one. They think that it would be very helpful to conduct a study for evaluation the eminence angle or better, the condylar guide. PMID- 2215484 TI - [Kinesiographic neuromuscular orthognathodontics: kinesiographic method after the Attinas]. AB - The Authors, after a brief mention to the historical evolution of the stream of thought and of the several operative approaches towards the gnatological problem, illustrate the main principles of Attina's new kinesiographic methodology. They underline the integrative value regarding the one adopted at present and its capacity to be able to enlarge the power of kinesiographic instrument. PMID- 2215485 TI - [Extreme simplification of treatment of Class II. Critical review after 15 years]. PMID- 2215486 TI - [Diagnostic evaluation of the soft tissue profile]. AB - The Authors report a cephalometric analysis of soft tissues profile to help the orthodontist to do a correct treatment plane referred to the three thirds of the face and not limited to the lower one only. This analysis is related to adult patients, and because the well known considerations about development of the soft tissues, it should be a predictable analysis of soft tissues profile at the end of growth. PMID- 2215487 TI - [Radiographic screening of asymmetry and postural changes in orthodontic patients]. AB - The role of OPM and of the teleradiography in the diagnosis of the asymmetries and of the postural problems of the orthodontic patients, is pointed out from this analysis on the group of 204 patients from mixed dentition to the adult age with different types of malocclusion. The evidence of a significant amount of patients with asymmetries and incorrected posture shows the utility of this radiological screening and gives advises for a therapeutic approach more corrected. PMID- 2215488 TI - [Epidemiological aspects of mandibular asymmetry in the developmental period]. AB - The prevalence of mandibular asymmetry in developmental age has been evaluated by a clinical and photographic survey. The signs of dysfunction increased with age from 14 to 34.5%. The heterogeneous predisposing or concurrent factors are discussed, with special attention for postural and breathing problems. PMID- 2215489 TI - [Echographic prenatal diagnosis of cleft lip and palate: orthodontic implications]. AB - The study of two cases of ultrasound prenatal diagnosis of cleft lip and palate and cleft lip, led the Authors to suggest the usefulness of first istance precocius correttive surgery in the immediate postnatal period. This correttive surgery not only allows the infant to be fed by natural vias, but it also facilitates the coordinated programming of successive final correttive surgeries by the plastic, the maxillofacial surgeons and the orthodontist. PMID- 2215490 TI - [Orthodontics and prosthetics: finishing dysfunctional cases]. AB - The Authors present the pathogenetic factors involved in the dysfunction of TMJ following the agenesia of permanent teeth. In these cases is very important to find and to maintain the therapeutic position by a repositioning splint. After this first stage it is necessary to correct the position and the relationship of the teeth in order to rearrange the space for the prosthetic reconstruction. PMID- 2215491 TI - [Medico-legal aspects of orthodontics]. AB - The deep technological innovations undergone by the medical profession, the changed relationships between physician and patient, the ever-growing attention given by public opinion to sanitary problems, as well as the growing expectation for the positive results of all me actions have determined, specially in these last years, medico-legal problems connected to the different spestic medico surgery activities, so that also the ortodo is called to a constant comparison not only with ethical deontological problems, but with the juridical ones too. PMID- 2215492 TI - [Evaluation of psychological factors in the etiopathogenesis of craniomandibular dysfunction in preadolescent and adolescent patients]. AB - The Authors have studied the psychological characteristics of 48 subjects of whom 17 with signs and symptoms of dysfunction, 12 only with signs of dysfunction and 19 without any dysfunction. From the data collected in our investigation it's possible to assume that there isn't difference (F test) about the psychological profile between this 3 groups of subjects. PMID- 2215493 TI - [Clinico-radiographic evaluation of relations between the spinal curve and malocclusion]. AB - Authors examined 36 children with kyphosis, lordosis and malocclusions. Taking also radiographs into account, a statistical study has been done. Three significant correlations were found: between lordosis and ANB, lordosis and SNA and between FR and CV Angle. The last one was a confirmation of a previous study by Solow. PMID- 2215494 TI - [New directions in cranio-cervico-mandibular cephalometry]. AB - A pilot survey has been conducted on a sample of 22 adolescents in order to correlate the cranio-facial morphology and the condylar position with the mandibular posture, cranio-cervical posture and airway adequacy. Cephalograms extended to the cervical column and oblique lateral trans-cranial X-Rays with the standard projection has been adopted. The use of specific cephalometrics parameters allowed to separate the sample in sub-groups with similar variables and to obtain diagnostic indications. The utility of an analysis not only cranio basal but extended to the cranio-cervical, intercervical, cervico-mandibular and hyoid parameters has been demonstrated. PMID- 2215495 TI - [Relationship of the articular eminence and the occlusal plane in TMJ dysfunction]. AB - Previous cephalometric studies do not adequately evaluate or determine anatomical features that characterize patients who are affected by temporomandibular dysfunction. The findings from this research appear to document a distinct correlation between the articular eminence and the posterior occlusal plane between symptomatic or asymptomatic patients. The eminence-occlusal plane angle is statistically smaller in the dysfunctional TMJ group than in the normal TMJ group. No other distinctive features are found in conventional cephalometric measurements between the two groups. The use od the eminence-occlusal plane angle could be necessary in the orthodontic practice and in the temporomandibular management to evaluate potential or actual TMJ problems. PMID- 2215496 TI - [Histology of the cartilage of the human fetal condyle]. AB - The Authors have examined with optical microscopy the articular cartilages from the supero-posterior area of the mandibular condyles of ten TMJ of 5 human fetuses. In this study have been shown the cellular components of the 3 outer areas of the condyle. Further it has been pointed out that the fibrous lining of the cartilage is not only composed of collagen fibrils, proteoglycans and fibroblasts but also contains elastic fibers. PMID- 2215497 TI - [Interceptive treatment of Class III in the deciduous dentition]. PMID- 2215498 TI - [The possible influence of bad habits on tooth morphogenesis. Clinical case]. AB - Thumb sucking, if continued beyond the age of two, is commonly acknowledged to compromise correct craniofacial development, with consequent dental malposition. The observation of a deciduous central incisor morphology, lost traumatically by a thumb-sucking three years old boy with an apparent open-bite, makes us think this bad habit can influence teeth morphogenesis too. PMID- 2215499 TI - [Cephalometric study of skeletal-facial changes in oral respiration from obstruction]. PMID- 2215500 TI - [Gnathologic-orthodontic protocol for Class II, division 1 with TMJ dysfunction]. AB - The Authors present a case of Class II Division I malocclusion associated with TMJ dysfunction and treated with a gnathologic-orthodontic approach. The protocol involves five steps: extraction of third molars because not useful in the orthodontic treatment, placement of a edgewise appliance following the Tweed technique, use of a neuromuscular deprogramming appliance, an orthopedic appliance associated with physiotherapy. PMID- 2215501 TI - [Why not try to move on ankylosed tooth orthodontically?]. AB - Due to presence of rigid inorganic matrix, mechanical perturbations cannot affect the bone blood supply or deform osteocytes. Because convincing evidence that bone can directly perceive mechanical forces in lacking, we hypothesize that mechanical perturbations can only elicit remodeling by acting through a soft tissue envelope. These soft tissue envelopes are the periodontal ligament, periosteum, fibrous tissues that can form around implants, sutures and the like. Fibroblast, preosteoblast, and mesenchymal cells are composing the envelopes. It is possible that these cells are indeed responsible for bone remodeling subsequent to forces application. PMID- 2215503 TI - [Colon sonography--a new method in the diagnosis of Crohn disease and ulcerative colitis]. AB - The entire length of the colon, starting at the recto-sigmoid junction and ending at the cecum, can be visualized sonographically following retrograde water instillation into the colon. Using this method it is possible to evaluate in detail the lumen, the intestinal wall and the surrounding connective tissue. Severe active colonic Crohn's disease and ulcerative colitis can be detected by diagnostic sonography of the colon with a sensitivity of 91% and 89% respectively. Crohn's disease can be differentiated from ulcerative colitis in 86% of the cases by means of colonic sonography. Transabdominal sonography of the fluid-filled colon is a new diagnostic procedure especially in children with Crohn's disease and ulcerative colitis. PMID- 2215502 TI - [Circulatory monitoring in very low birth weight infants using Doppler sonography]. AB - Doppler-ultrasonography measures blood flow velocity, which is proportional to blood flow if the vessel's diameters remain constant. Perfusion of brain, kidneys and gut can thus be estimated by transcutaneous ultrasonography at specific locations on the internal-carotid artery, renal artery and upper mesenteric artery. Cardiac output can be derived from measurements taken on the ascending aorta. The procedures of measurement are easy to learn, but interpretation is more critical. Doppler-ultrasonography has been applied in persistent ductus arteriosus, asphyxia, hyperventilation, brain death, impact of drugs on brain circulation, seizures, hydrocephalus, and shock. Future aims are the development of miniaturized doppler-sensors with low energy output for continuous monitoring, and the definition of guidelines for clinical applications. PMID- 2215504 TI - [Sonographic neonatal screening of the hip joint--luxury or necessity?]. AB - Based on the ultrasound investigation of 19,666 babies (1981-1988), 6341 of them directly at the maternity ward, we picked out the group of sonographically unstable or decentered hip joints, which must be treated instantly. Almost 50% of these hips did not show any clinical signs of instability! At follow-up the subgroup of sonographically screened hip joints showed optimal results after consequent earliest treatment: 100% physiological results of CE-angle (Wiberg and Engelhardt), no femoral head necrosis. Ultrasound screening is the only tool to detect definitely all newborn hips requiring therapy. Earliest treatment is the pre-condition of anatomical healing up. Thus--a general sonographic newborn screening is indispensable. PMID- 2215505 TI - [Direct genetic diagnosis in cystic fibrosis]. AB - The recent cloning of the cystic fibrosis gene and the simultaneous identification of the predominant mutation enabled direct gene diagnosis in the majority of all CF families. We demonstrate the superiority of now available direct genotyping in five individual cases. PMID- 2215506 TI - [Analysis of alpha 1-antitrypsin deficiency using DNA methods]. AB - Deficiency of alpha 1-antitrypsin can be diagnosed by DNA methods that are quick and also give reproducible results. Direct DNA analysis of the M, S, and Z alleles of the alpha 1-antitrypsin gene is possible when two molecular biology techniques are combined: a part of the gene is enzymatically replicated according to the pattern of the human DNA that is to be investigated. On hybridization with the various allele-specific pieces of synthetic DNA the copies that have come about in this way give a signal corresponding to the genotype. Only a small amount of material (0.5 microgram DNA) is needed for the investigation. This method is thus suitable for prenatal diagnosis when this is requested by members of a family known to be affected. A total of 53 samples were typed and investigations were carried out in six families. PMID- 2215507 TI - [Determination of C-reactive protein (CRP) in capillary blood--a comparison with the CPR level in venous serum]. AB - C-reactive protein (CRP) has served as a reliable indicator of infectious and inflammatory diseases for a long time. Sequential CRP determinations offer a useful means of monitoring clinical courses and therapeutic effects in patients of any age as its serum concentrations correlate well with clinical symptoms. Especially in pediatric patients, however, venous blood sampling causes many problems. Thus, in our study a new method of CRP analysis from capillary plasma samples was tested and compared with CRP determinations from venous serum samples. 101 pairs of samples simultaneously obtained from 64 pediatric and neonatal patients (mean age of 5.8 months: min. 1 day, max. 5.5 years) were analyzed and compared. A good correlation (r = 0.967) was found for the whole range of measured CRP-concentrations (5-175 mg/l), showing a linear relationship between both methods. Results were analyzed by chi 2-test. Using a cutoff level of 5 mg/l, a sensitivity of 96%, a specificity and a positive predictive value of 98% each and an efficiency of 97% was found. Thus, the CRP determination from capillary blood samples offers a reliable method and a useful alternative for conventional analysis from venous serum. PMID- 2215508 TI - [Acquired dysfibrinogenemia in a child in the course of a liver disease]. AB - This report documents the results of coagulation studies in a 15-year old boy with hepatic disease of possibly autoimmune origin. Thrombin- and reptilase clotting times were prolonged. The results of fibrinogen determinations with different methods (heat precipitation, kinetic assay according to Clauss) lead to the assumption of a qualitative anomaly of fibrinogen (dysfibrinogenaemia). Investigations with purified fibrinogens from the patient and a healthy control confirmed this assumption. The thrombin clotting time of purified fibrinogen from the patient was clearly prolonged in comparison to the purified fibrinogen from a healthy control. The fibrin monomers of the patient exhibited impaired polymerization. No structural abnormalities were detected by electrophoretic techniques, particularly the thrombin-induced release of fibrinopeptides was found to be normal. The coagulation abnormalities resolved after glucocorticoid administration. PMID- 2215509 TI - [Tuberous sclerosis--rare pulmonary manifestations]. AB - We report on a twenty year old female patient with pulmonary involvement in tuberous sclerosis. According to the literature these patients seem to represent a unique subtype of tuberous sclerosis because of female predominance, age at diagnosis and especially the course of the disease, which comes to an end by the pulmonary changes. PMID- 2215510 TI - [Fulminant autoimmune cold-type hemolysis with marked elevation of monothermic cold agglutinins. Successful therapy with membrane plasmapheresis]. AB - Autoimmune hemolytic anemia associated with cold autoantibodies is rare in infancy. In a 7 months old infant with severe hemolysis, a hemoglobin of 5.9 g/dl and a cold agglutinin titer of 1:8000, even the transfusion of warmed, packed red cells (37 degrees C) lead to hemolysis. Hemoglobin fell to 2.8 g/dl despite prevention of exposure to cold, parenteral steroids and immunoglobulins. Cold agglutinin titer fell to 1:8 after plasma separation. Subsequent transfusion did not lead to hemolysis and permanent remission was achieved. PMID- 2215511 TI - [The 86th annual meeting of the German Society of Pediatrics, September 16-19, 1990, Koln together with the 28th annual meeting of the German Society of Pediatric Surgery, September 17-19, 1990, Koln and 42nd annual meeting of the German Society of Social Pediatrics, September 18-19 1990, Koln]. PMID- 2215512 TI - Interleukin-2, killer cells and cancer therapy: an overview. PMID- 2215513 TI - Lessons from the clinical trials of interleukin-2. AB - The initial results of interleukin-2 (IL-2) therapy in man are reviewed from the perspective of how they conform to predictions from preclinical studies. These preclinical models predict that tumors will vary in their susceptibility to IL-2 therapy and will be most successfully treated at lower tumor burdens. In addition, the dose and schedule of IL-2 are important for successful therapy. Host-related factors, including the presence of suppressor activities, may also be important. In these models, the addition of other cytokines, including interferon-alpha or tumor necrosis factor, to IL-2 can enhance antitumor activity. The concomitant administration of ex vivo IL-2-activated lymphokine activated killer cells or tumor-infiltrating lymphocytes also enhances the IL-2 antitumor effect. Clinical trials addressing all of these issues have been completed or are underway; the results suggest overall that the preclinical models are predictive, with both host- and tumor-related factors as well as such IL-2-therapy-related factors as dose, schedule, route and the use of additional agents all playing a role in the success of therapy. A more complete understanding of the mechanisms of response and resistance involved in this therapy will facilitate the rational development of more effective and less toxic IL-2-based therapy of human malignancy. PMID- 2215514 TI - Role of human circulating and tumor-infiltrating lymphocytes in cancer defense and treatment. AB - We have analyzed the anticancer efficacy of various subsets of human circulating and tumor-infiltrating lymphocytes (TIL). These studies showed that circulating natural killer (NK) cells mediate the most potent oncolytic activity against a variety of tumor targets, after enrichment or stimulation with interleukin-2 (IL 2). Interestingly, NK cell oncolytic activity was directed also against tumor targets frequently designated as 'NK-resistant'. This indicates that NK cells display a broader spectrum of killing than is commonly recognized. TIL did not display any tumoricidal activity when unstimulated, but acquired cytotoxic potential after activation with IL-2. Comparative studies of TIL and circulating lymphocytes from patients with ovarian cancer demonstrated that these two groups of lymphocytes manifested similar levels of cytotoxicity and the same spectrum of target cell killing. No specificity in autologous tumor cell killing was displayed by TIL; instead, TIL were effective against autologous as well as allogeneic tumor targets. The lack of TIL tumor specificity was not detected only in ovarian tumors, but was manifested also in renal- and squamous-cell cancers. Characterization studies demonstrated that the primary oncolytic cells in the periphery and among TIL are NK cells. T lymphocytes displayed some, but rather negligible cytotoxic activity. In contrast, when IL-2-activated NK and T cells were analyzed for lytic activity against normal hematopoietic cells, T cells displayed high levels of bone marrow killing. The anti-bone marrow lytic activity of IL-2-activated T lymphocytes may be harmful after therapy with conventionally prepared lymphokine-activated killers. In light of these observations, new directions to adoptive immunotherapy are discussed. PMID- 2215515 TI - Involvement of granule proteins in T-cell-mediated cytolysis. AB - Cytolytic T lymphocytes (CTL) and large granular lymphocytes contain dense cytoplasmic granules which, when isolated, are lytic for a variety of target cells. Granule proteins are released from the effector cell upon target cell interaction, further suggesting that they play a role in the cytolytic mechanism. Major proteins in CTL granules are a family of serine esterases (granzymes) and a pore-forming protein called perforin (cytolysin). Despite structural similarities between functionally conserved regions of perforin and the ninth component of complement (C9), these two lytic molecules are clearly distinct in their mode of target cell recognition. Perforin, unlike C9, is not dependent on a protein receptor molecule but binds to the target cell membrane via phosphorylcholine in a Ca2(+)-dependent manner. Here, we discuss the stimulus-secretion model for T cell-mediated cytotoxicity with respect to our current understanding of perforin and the granzyme proteases. PMID- 2215516 TI - Sensitivity of ovarian tumor cells to effector cells generated by various biological response modifiers. AB - The sensitivity of freshly derived human ovarian tumors (FOT) to various allogeneic cytotoxic effector cells stimulated by recombinant interleukin 2 (rIL 2), recombinant interferon alpha 2 (rIFN-alpha 2), OK-432, and concanavalin A was examined using the 51Cr release assay. Peripheral blood lymphocytes (PBL) of normal female donors were used as source of effector cells. Incubation of PBL with these biological response modifiers for 24 h generated effector cells with high natural killer activity, and only 20% (1/5) of the FOT examined were susceptible to lysis. By contrast, 83% (5/6) of the FOT were sensitive to lymphokine-activated killer (LAK) cells generated by rIL-2. OK-432 and concanavalin A activation of PBL also generated cytotoxic cells, though the cytotoxic activity against FOT was much less than that obtained by LAK cells. The addition of OK-432 to LAK culture medium containing rIL-2 generated effector cells with higher cytotoxicity against FOT than cultures with IL-2 alone. However, the addition of rIFN-alpha 2 in LAK culture medium resulted in the generation of effector cells with lower cytotoxicity. The addition of rIL-2, rIFN alpha 2, or OK-432 to LAK cells during the in vitro cytotoxicity assay had no significant effect. When FOT target cells were pretreated with OK-432 they became more sensitive to LAK than nontreated tumor cells. However, pretreatment with rIL 2 or rIFN-alpha 2 did not influence cytolysis. These results suggest that the generation of LAK cells in vitro using rIL-2 plus OK-432 may be a more effective way to prepare these cells for adoptive immunotherapy in the treatment of ovarian cancer. PMID- 2215517 TI - [Phototherapy of endogenous depression. A contribution to chronobiologic research in psychiatry]. PMID- 2215518 TI - [DNA distribution in fractions differing in the strength of association with nuclear matrix during activation of DNA endonucleases in cell nuclei and treatment with nuclease S1]. AB - Influence of activation of Ca2+/Mg2(+)-dependent, Mn2(+)-dependent, Mg2(+) dependent and acidic endogenous DNAses on distribution of DNA in fractions differing in tightness of association with the nuclear matrix has been investigated. In the intact cell nuclei all types of DNA-protein bonds were obscured by a tight bonding of DNA with the proteins of replicative complex. Activation of endogenous nuclease activities caused detachment of a significant chromatin fraction from the nuclear matrix, fraction of DNA remained attached to the replicative complex, small fraction of DNA was bound to the nuclear matrix with a less tight bond. The endogenous nucleases are supposed to make cuts mainly in distal parts of the chromatin loops and do not affect the replicative complex, where the tight DNA-matrix bond is localized. Single-strand DNA-specific S1 nuclease preferably attacks the latter site. PMID- 2215519 TI - [Transduction of chromosome and plasmid markers of bacteriophage P1 in pseudotuberculosis pathogen]. AB - A clone of bacteriophage P1 clr100 cml has been isolated capable of the general transduction in the cells of pseudotuberculosis causative agent. The genetic transfer of the 6 Md pesticinogenicity plasmid by the bacteriophage has been used as a model to demonstrate the possibility of transduction. The bacteriophage used has been shown to be efficient in interspecies transduction between yersinia. PMID- 2215520 TI - [Construction of recombinant genes coding for products containing the fragment of Staphylococcus aureus protein A and the fragment of Pseudomonas aeruginosa exotoxin A]. AB - The genes coding for Pseudomonas aeruginosa exotoxin-A and Staphylococcus aureus A-protein have been cloned. Different fragments of the genes were subcloned on the plasmid vestors. The plasmids pAPA4 and pAPA42 have been constructed. The plasmids are coding for the hybrid protein which consists of the immunoglobulin binding A-protein domain at its NH2-terminus and the catalytically active fragment of exotoxin-A at its COON-terminus. The hybrid gene is expressed in Escherichia coli cells under the control of lambda cro-gene expression elements (pAPA42) or lac-operon expression elements (pAPA4). The latter proved to be most productive. PMID- 2215521 TI - [Genetic determinants of restriction-modification systems in bacteria]. AB - The recent data on the molecular arrangement and functioning of the genetical determinants for the enzymes of restriction-modification systems are discussed. The problems of restriction endonucleases and methylases genes localization, regulation of activity of the genes for enzyme systems of the II type restriction modification, characteristics of the primary structure of the genes and phylogeny of restriction endonucleases and methylases are reviewed. PMID- 2215523 TI - Fundamental and molecular mechanisms of mutagenesis. PMID- 2215522 TI - Persistence of drug-induced chromosome aberrations in peripheral blood lymphocytes of the rat. AB - We have studied the persistence of pre-clastogenic lesions, detected as induced chromosomal aberrations, in rat peripheral lymphocytes at various time intervals after acute treatment with 3 different antineoplastic drugs: cyclophosphamide (CPA), 5-fluorouracil (5-FU) and adriamycin (AM). Single i.p. doses were administered to groups of rats and heart blood samples from each group were taken after 3, 12, 24 or 48 h or weekly up to 20 weeks later. The cytogenetic analysis was performed on lymphocytes cultured for 33 h after sampling. The results for CPA exposure (10 mg/kg) show that the yield of chromosome aberrations is maximal 3 h after the treatment (20 times the control level). For up to 8 weeks the values remain about 6 times the baseline; afterwards a decrease is observed and the control level is reached after 20 weeks. For 5-FU (50 mg/kg) a remarkable increase (13-fold) in chromosomal damage is observed at the first sampling time. Within 48 h the effect is drastically reduced but persistent (3 times the control level), and the level returns to spontaneous values 1 week later. AM treatment (2 mg/kg) induced an increase of about 8 times the control level at 3 h post exposure. The clastogenic effects remained at a detectable level for 1 week (about 6 times the control level at all sampling times); 2 weeks after the treatment the control level was found. A parallel analysis was performed on bone marrow cells. In this tissue the clastogenic effects of the treatments were maximal, as in lymphocytes, at the first sampling time (20-25 times the control level) and were no longer detectable within 72 h after exposure, irrespective of the administered drug. PMID- 2215524 TI - DNA polymerase alpha from HeLa cells synthesizes DNA with high fidelity in a reconstituted replication system. AB - To determine the contribution that DNA polymerase alpha makes to the overall DNA replication fidelity in mammalian systems, we measured the fidelity of replication of the SV40-based shuttle vector, pZ189, in a reconstituted in vitro DNA replication system which contained purified HeLa DNA polymerase alpha (in addition to single-stranded DNA binding protein, topoisomerase II, DNA ligase, 5' ---3' exonuclease, ribonuclease H, and SV40 T-antigen). We found that DNA polymerase alpha is highly accurate when carrying out bidirectional replication in this system. This high fidelity of replication by DNA polymerase alpha in the reconstituted replication system contrasts with a relatively low fidelity of gap filling DNA synthesis on the same target gene by purified HeLa cell DNA polymerase alpha in the absence of other replication factors. The fidelity of DNA replication by DNA polymerase alpha, although relatively high in the reconstituted system, is about 4-fold lower than DNA replication in a crude HeLa cell extract which contains additional replication factors including DNA polymerase delta. These results demonstrate that DNA polymerase alpha has the capacity to replicate DNA with high fidelity when carrying out semiconservative DNA replication in a minimal reconstituted replication system, but additional cellular factors not present in the reconstituted system may contribute to the higher replication fidelity of the crude system. PMID- 2215525 TI - The DNA cleavage induced by a chromium(V) complex and by chromate and glutathione is mediated by activated oxygen species. AB - The number of strand breaks induced by the combination of chromate and glutathione (GSH) in PM2 DNA was effectively reduced upon addition of the hydroxyl radical scavengers dimethyl sulphoxide (DMSO), formate and benzoate. Administration of catalase also led to a depression of DNA degradation whereas superoxide dismutase (SOD) had very little influence. Essentially the same results were obtained in experiments employing a chromium(V) complex Na4(GSH)4Cr.8H20, which is an intermediate chromium species isolated from the reduction of chromate by glutathione. DNA cleavage was dependent on the presence of iron (FeCl3). When compared with the number of breaks produced by FeCl3 and GSH alone, chromate stimulated the generation of single-strand breaks. These findings suggest that hydroxyl radicals are one ultimate DNA cleaving agent in both reactions. A reaction scheme for the production of hydroxyl radicals is proposed. PMID- 2215526 TI - Localization of deletion breakpoints in radiation-induced mutants of the hprt gene in hamster cells. AB - DNA was analysed from a large set of hamster hprt gene mutants, some induced by ionising radiations and others occurring naturally, to identify those with large alterations in part of the gene. DNA from these mutants was restricted further with different endonucleases and probed to establish the patterns of restriction fragments remaining. Of 15 mutants characterized, one showed a duplication of part of the 5' end of the gene, and the remainder showed deletions of various sizes. It was possible to approximately locate the breakpoints of the deletions by comparison of fragment patterns to a recently-established map of the hamster gene. The relatively small number of mutants examined precludes rigorous analysis of the distribution of breakpoints in the hprt gene, but taken with other recent studies of deletion mutagenesis it is suggested that non-random induction or selection of this type of mutation may occur. PMID- 2215527 TI - Molecular characterization of X-ray-induced mutations at the HPRT locus in plateau-phase Chinese hamster ovary cells. AB - CHO-K1 cells were irradiated in plateau phase to determine the effect of dose, dose fractionation, and delayed replating on the type, location and frequency of mutations induced by 250 kVp X-rays at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus. Independent HPRT-deficient cell lines were isolated from each group for Southern blot analysis using a hamster HPRT cDNA probe. When compared with irradiation with 4 Gy and immediate replating, dose fractionation (2 Gy + 24 h + 2 Gy) the entire gene. Since an increase in survival was noted under these conditions, these data suggest that repair of sublethal and potentially lethal damage acts equally on all premutagenic lesions, regardless of type or location. Differences in the mutation spectrum were noted when cells were irradiated at 2 Gy and replated immediately. The location of the deletion breakpoints was determined in 15 mutants showing partial loss of the HPRT locus. In 12 of these cell lines one or both of the breakpoints appeared to be located near the center of the gene, indicating a nonrandom distribution of mutations. These results indicate that damage induced by ionizing radiation results in a nonrandom distribution of genetic damage, suggesting that certain regions of the genome may be acutely sensitive to the mutagenic effects of ionizing radiation. PMID- 2215528 TI - Studies on the effect of ascorbic acid and selenium on the genotoxicity of nitrofurans: nitrofurazone and furazolidone. AB - The genotoxic properties of nitrofurazone and furazolidone were studied using the Ames test and SOS-chromotest. Both compounds were found to act as strong mutagens on the TA97 and TA102 strains of S. typhimurium and to induce the SOS-repair system in the PQ37 strain of E. coli. A good concordance was found between the mutagenic activity and the ability to induce the SOS system. Ascorbic acid and sodium selenite only very slightly lowered the genotoxic effect of the 2 nitrofurans studied both in the Ames test and in the SOS-chromotest. PMID- 2215529 TI - Several known indole compounds are not important precursors of direct mutagenic N nitroso compounds in green cabbage. AB - In this study we investigated the role of indole-3-acetonitrile, indole-3 carbinol, indole and tryptophan in the formation of N-nitroso compounds in green cabbage extracts. Green cabbage extracts were separated by gel permeation chromatography. Fractions were treated with nitrite, tested for mutagenicity and analysed for total N-nitroso content. Fractions in which spiked indole-3 acetonitrile, indole-3-carbinol, indole and tryptophan eluted appeared to be low in mutagenic activity and contained relatively small amounts of N-nitroso compounds. To detect indole compounds other than the ones used in the gel permeation chromatography experiments, high-performance liquid chromatography and gas chromatography-mass spectrometry analyses were performed of green cabbage extracts. Indole-3-carboxaldehyde was found to be the most commonly occurring indole compound, but it did not show direct mutagenic activity upon nitrite treatment. Indole-3-acetonitrile was the second most common compound; although it was mutagenic after nitrite treatment, its contribution to the mutagenicity of nitrite-treated green cabbage was roughly estimated to be only 2%. No other indole compounds were detected. From this study we conclude that neither the tested indole compounds nor indole-3-carboxaldehyde play a significant role in the formation of direct mutagenic N-nitroso compounds in nitrite-treated green cabbage extracts. PMID- 2215530 TI - Induction of dominant lethal mutations by combined X-ray-acrylamide treatment in male mice. AB - The induction of mutations following combined treatment with acrylamide (AA) plus X-rays has been determined using the dominant lethal mutations test in Pzh:SFISS male mice. Combinations of a mutagenic dose of both agents (1.00 Gy, 125 mg/kg b.w.) and a non-mutagenic dose, i.e., a dose that alone does not produce dominant lethals (0.25 Gy, 25 mg/kg b.w.), were used. For the discussion of the effects of combined action of X-rays and acrylamide the term 'enhancement in risk' was used whenever the effects observed after combined exposure significantly exceeded the sum of the effects produced separately by the agents. Such an enhanced risk has been observed in late spermatids after combined action of X-rays and AA at non mutagenic doses, and in spermatozoa, spermatids and late spermatocytes after exposure to mutagenic doses. PMID- 2215531 TI - A 5-fold reduction in sister-chromatid exchange following implantation of mouse embryos is not directly related to the expression of embryonic genes responsible for oxygen radical metabolism. AB - We studied the spontaneous sister chromatid exchange (SCE) frequencies in mice at different stages of development; early preimplantation: 2 days post conception (p.c.); late preimplantation: 4 days p.c.; post implantation: day 10 and 13 p.c. The SCE level in preimplantation embryos is 5 times higher than any of the stages following implantation. The explanation for such observations may include a direct impact of maternal circulatory system as a result of implantation or onset of expression of a set of embryonic genes. Here, we studied the expression and developmental profile of the three enzymes of oxygen radical metabolism (superoxide dismutase, glutathione peroxidase, and catalase) during development. Our results suggest that the onset and increase in the activity of these enzymes with in-utero differentiation, development and growth is not directly associated with the drop in SCEs/cell following implantation of the embryos. This unique developmental phenomenon may be mediated by the maternal circulatory system or expression of some other embryonic genes, possibly the genes involved in DNA repair. PMID- 2215532 TI - Chromosome aberrations, sister-chromatid exchanges and cell-cycle kinetics in human peripheral blood lymphocytes exposed to organoselenium in vitro. AB - The ability of 2 synthetic organoselenium compounds, a dimer of p methoxybenzeneselenol (DPMBS) and benzylselenocyanate (BSC), to induce sister chromatid exchanges (SCE) and chromosome aberrations (CA) as well as to alter the progression of the cell through mitosis has been investigated in cultured human lymphocytes. Cultures treated with the highest concentration (2.27 x 10(-5) M) of the 2 compounds exhibited about a 3-fold increase in the level of SCE and about 2 3-fold increase in the incidence of CA. In addition, the 2 selenium compounds led to an inhibition of cell proliferation as was evidenced by the depression of the proliferation rate index (PRI). PMID- 2215533 TI - Structure-activity relationships for the mutagenic activity of tricyclic intercalating agents in Salmonella typhimurium. AB - A total of 25 different tricyclic DNA-intercalating chromophores bearing a common -CONH(CH2)2N(CH3)2 solubilizing sidechain have been compared with the 'classical' frameshift mutagen 9-aminoacridine for their ability to induce revertants in Salmonella typhimurium strain TA1537 (sensitive to frameshift mutation by acridine mutagens). The compounds showed varying levels of activity in this strain. For the fused linear and fused angular tricyclics, activity varied from zero to similar levels to 9-aminoacridine, but with no discernable relationship between activity and either structure or the measured physico-chemical properties. However, the '2-1' tricyclic compounds had essentially no mutagenic activity. Since several of these compounds have high in vivo antitumor activity, this is useful knowledge. PMID- 2215535 TI - Use of a composite polyfunctional model electrophile as a probe to analyze the performance of an artificial intelligence structure-activity method. AB - The CASE structure-activity relational method was applied to the model polyfunctional electrophile proposed by Ashby and associates. The predicted activities from data bases of 'structural alerts', mutagenicity in Salmonella and rodent carcinogenicity were compared. It was thus found that the predictive efficacy of CASE was increased when it employed a combination of human and artificial intelligence, as exemplified by the CASE analysis of 'structural alerts. PMID- 2215536 TI - Chromosome-type exchange aberrations are induced by inhibiting repair of UVC induced DNA lesions in quiescent human lymphocytes. AB - Human lymphocytes in the quiescent stage were UVC-irradiated and then incubated for 90 min in the presence of the DNA-repair inhibitor ara-C. The cells were then cultured and analyzed for chromosome aberrations. A single treatment with UVC or ara-C gives rise to a very low yield of dicentrics, whereas the combined treatment can induce a high frequency of these chromosome-type aberrations. The yield in the combined treatment is approximately proportional to the square of the UVC fluence in the range 1-3 J/m2. In addition, the experiments demonstrate that synergistic effects arise when cells are treated with UVC + ara-C and then exposed to X-rays. The results can be explained on the assumption that the UVC + ara-C treatment induces DNA double-strand breaks which, to the first approximation, are randomly distributed over the chromosomes. These breaks are able to interact with each other as well as with X-ray-induced DNA double-strand breaks to form a chromosome-type exchange aberration. PMID- 2215534 TI - Metabolic activation of quercetin mutagenicity. AB - The mutagenicity of quercetin was reinvestigated using the Salmonella/microsome test. The mutagenicity of quercetin was enhanced by the cytosolic fraction of liver extract (S100), or by ascorbate, and even more by the complete liver supernatant (S9) in the presence of cofactors (NADP and glucose-6-phosphate). The formation of metabolites by the S9 enzymes was demonstrated by reverse-phase HPLC. PMID- 2215537 TI - On the time course of the interactions between DNA breaks in the production of a radiation-induced chromosome exchange aberration. AB - Quiescent human lymphocytes were X-irradiated and allowed to repair for various times at 37 degrees C before the cells were challenged with the DNA-repair inhibitor ara-C. The observed yield of chromosome exchange aberrations (dicentrics) was about twice the yield induced by X-rays alone, if ara-C was added immediately after irradiation. The yield as a function of the repair time between X-irradiation and ara-C treatment decreased with a half-life of 15-30 min and was almost down to the baseline yield for X-rays alone after 1 h. This shows that an exchange aberration can be formed from a short-lived DNA break. In contrast, previously published results from dose-split experiments demonstrate that the half-life of the interacting DNA breaks is of the order of several hours. A model is proposed which can account for the different estimates of the time course of the interactions involved in the process which leads to an exchange aberration. PMID- 2215538 TI - The load of genetic and partially genetic diseases in man. III. Mental retardation. AB - This paper summarizes estimates of detriment associated with different etiologic categories of mental retardation (MR) in Hungary. The basic data derive from an earlier study carried out in Budapest on 1276 school-age mentally retarded children (with some etiologic reclassification based on recent studies). Detriment associated with these different categories of MR is expressed in terms of years of lost and impaired life. About 30 per 10(3) school-age children in Hungary are mentally retarded (mild + severe MR), one-tenth of whom have severe MR (IQ less than or equal to 50); 50% of the latter are institutionalized. The breakdown on the basis of etiology is as follows: gene mutations and chromosomal abnormalities, about 4 per 10(3); 'familial' (multifactorial) causes, 12 per 10(3); adverse pre-, peri- and post-natal causes, 11 per 10(3); and 'causes as yet unknown', the remainder. The estimates of mean number of years of lost life range from 42 to 68 (depending on the etiologic category), with an overall mean of 58. The total number of years of lost life is about 36,000 per 10(4) live births of which over 70% is due to pre-, peri- and post-natal causes, 18% due to 'familial' causes and the remainder due to Mendelian and chromosomal diseases. The total number of years of impaired life is about 7300 per 10(4) livebirths, 50% of which is due to 'familial' causes. While admittedly approximate, these estimates suggest that detriment associated with MR-related causes is not inconsiderable. Additionally, they provide some indication of causes of MR which are minimizable. PMID- 2215539 TI - Analysis of interactions between mutagens, I. Heat and ultraviolet light in Saccharomyces cerevisiae. AB - A new mathematical approach to the description of interaction data (Ager and Haynes, 1987) is applied here to the interaction between heat and ultraviolet light (UV) in Saccharomyces cerevisiae. A strong synergism for cell killing is found to be associated with large increases in gene conversion (of up to 8-fold), and mutation (of up to 14-fold). Analysis of the interaction data for both wild type and repair-deficient strains indicates that the heat-UV synergism arises via the inhibition of two different repair pathways. Unambiguous conclusions regarding the molecular mechanisms by which these repair processes are inhibited cannot be drawn on the basis of dose-response data alone. However, this approach does enable one to make well defined, empirical comparisons of the nature and kinetics of such interactions. PMID- 2215540 TI - Analysis of interactions between mutagens, II. Ethyl methanesulfonate and ultraviolet light in Saccharomyces cerevisiae. AB - The results of this study indicate the existence of a strong interaction between ethyl methanesulfonate (EMS) and ultraviolet light (UV) for cell killing in the yeast Saccharomyces cerevisiae. Conversely, mutation and gene conversion frequencies observed for the combined treatment of EMS and UV do not deviate significantly from that expected on the basis of simple additivity. Studies involving repair-deficient mutants (rad mutants) reveal that the synergistic interaction for cell killing depends on RAD52 function (recombinational repair), but not on RAD3 function (excision repair). On the basis of this analysis, the interaction between EMS and UV in S. cerevisiae might arise from the inhibition of double-strand break repair by one, or both agents. PMID- 2215541 TI - The mutagenic effects of diacridines and diquinolines in microbial systems. AB - Two series of difunctional DNA-intercalating agents (diacridines and diquinolines) were tested for mutagenic properties in Salmonella typhimurium strain TA1537, and for 'petite' mutagenesis activity in Saccharomyces cerevisiae, and also compared in terms of their structural, lipophilic and DNA-binding properties. Diacridines with only a short chain length were monointercalators, while those with an alkyl linker chain longer than C6 were bisintercalators. Although the bisintercalators especially bound very tightly to DNA, none of these compounds was as effective a frameshift mutagen in TA1537 as the parent chromophore 9-aminoacridine. However, the two (monointercalating) diacridines of shortest chain length were still able to cause frameshifts, and this ability returned (albeit weakly) in the bisintercalators of longest chain length. Although 9-aminoacridine showed no ability for 'petite' mutagenesis, the diacridines of longer chain length were very effective in causing this mitochondrial event. In the quinoline series, both the parent chromophore (4 aminoquinoline) and all the diquinolines were weak monointercalators. None of these compounds showed any ability for frameshift mutagenesis, although some were very weak mitochondrial mutagens. It is concluded that linking two acridines produces compounds whose mutagenic properties might have been predicted from our current knowledge of the parent molecules. However, despite a similar ability to intercalate DNA, the diquinolines show no resemblance to acridines in their mutagenic properties. PMID- 2215542 TI - Kinetochore identification in micronuclei in mouse bone-marrow erythrocytes: an assay for the detection of aneuploidy-inducing agents. AB - An in vivo micronucleus assay using mouse bone marrow for identifying the ability of chemicals to induce aneuploidy and/or chromosome breaks is described. Micronucleus formation in bone-marrow erythrocytes of mice is commonly used as an index for evaluating the clastogenicity of environmental agents. However, micronuclei may also originate from intact lagging chromosomes resulting from the effect of aneuploidy-inducing agents. We have used immunofluorescent staining using anti-kinetochore antibodies to classify micronuclei for the presence or absence of kinetochores. Micronuclei positive for kinetochores are assumed to contain intact chromosomes and result from induced aneuploidy; while those negative for kinetochores contain acentric chromosomal fragments and originate from clastogenic events. The assay was evaluated using X-irradiation (a known clastogen) and vincristine sulfate (an aneuploidy-inducing agent). A dose-related response for the induction of micronuclei was observed for both agents. Micronuclei induced by X-irradiation were negative for kinetochores while the majority of the micronuclei resulting from vincristine treatment contained kinetochores. Thus, the micronucleus assay in combination with immunofluorescent staining for kinetochores may provide a useful method to simultaneously assess the ability of chemicals to induce aneuploidy and/or chromosome breaks. PMID- 2215543 TI - Knowledge-based battery design of short-term tests based on dose information. AB - A construction of batteries of short-term tests (STTs) is described which is based on a classification of 73 chemicals in regard to their carcinogenicity. The 73 chemicals were studied within the U.S. National Toxicology Program (Ashby and Tennant, 1988). The batteries are validated using the classification of 35 additional chemicals. They are defined by logically structured combinations of rules. The single rules are defined by the z-scores of the logarithmic values of the limiting doses obtained from the 4 in vitro STTs used in the study by Ashby and Tennant. The limiting dose is defined as the lowest effective dose or the highest ineffective dose (Waters et al., 1987). The batteries are constructed by minimizing the number of disagreements with the classification by Ashby and Tennant. Compared with the results obtained from single STTs, 2 batteries of 3 STTs have higher concordances with the carcinogenicity data, namely 70% for the NTP data and 74-77% for the independent test data. In addition, a theoretical result shows that the proposed battery design, for a large enough learning set of chemicals, leads to results which are replicated with high probability on a large enough validation set. Based on the first results obtained with a limited number of chemicals it is concluded that the knowledge-based battery design is worth further development. PMID- 2215544 TI - Salmonella test: relation between mutagenicity and number of revertant colonies. AB - This paper describes a model that relates the actual effect measured in the Salmonella test, i.e., the number of revertant colonies, to the mutation rate induced by a stable test compound having no side effects and acting without a time-lag. A maximum-likelihood estimator for the mutation rate is derived. Furthermore some side effects (mortality, increase in generation time, other mutations) are included in more extensive models. Side effects can cause a non linear dose-response relation. Factors delaying the effect of the compound lead to an apparently higher mutation rate if a higher histidine dose is applied or a smaller inoculum is used. Factors slowly decreasing the effect of the compound reverse this result. Secondary effects of the test compound on the bacteria result in a non-linear dose-response relationship. PMID- 2215545 TI - Detection of aneuploidy and aneuploidy-inducing agents in human lymphocytes using fluorescence in situ hybridization with chromosome-specific DNA probes. AB - The feasibility of utilizing fluorescence in situ hybridization with chromosome specific DNA probes as the basis of an assay to detect aneuploidy and aneuploidy inducing agents in interphase human lymphocytes has been investigated. The assay involves counting the number of hybridization regions in interphase cells to determine the number of copies of a specific chromosome of interest, 22,000 interphase nuclei from untreated 72-h lymphocyte cultures were examined following hybridization with probes for chromosomes 1, 7, 9, 17, X or Y. The combined frequencies of nuclei containing 0, 1, 2, 3 and 4 hybridization regions for the various autosomal chromosomes were 0.004, 0.084, 0.909, 0.003 and 0.001, respectively. Based on these frequencies, scoring 1000-2000 cells should allow detection of aneuploid cells with a 0.012 frequency of hyperdiploidy or a 0.11 frequency of hypodiploidy for a specific chromosome of interest (alpha = 0.05, beta = 0.80). This difference in test sensitivity is related to the higher frequency of cells with one apparent spot. A comparison of the ratio of hybridization region to nuclear area in the two-dimensional images used for this analysis indicates that an overlap of the two regions probably accounts for the high frequency of apparent monosomy observed in normal cells. Treatment with the aneuploidy-inducing chemicals, colchicine, vincristine sulfate and diethylstilbestrol resulted in significant dose-related increases in the number of nuclei containing 3 or more hybridization regions. Treatment with the clastogen sodium arsenite produced only a minor increase in apparently hyperdiploid cells whereas treatment with ionizing radiation, another potent clastogen, resulted in a significant increase in nuclei containing multiple hybridization regions. These results suggest that ionizing radiation is an aneuploidy-inducing agent under these conditions although chromosomal breakage within the hybridization region may account for a portion of the increased frequency of nuclei with multiple hybridization regions. These results indicate that the use of fluorescence in situ hybridization with DNA probes is capable of detecting aneuploid cells occurring at relatively low frequencies within a population of cells. Assays based on these techniques should facilitate a more rapid identification of aneuploidy-inducing environmental and therapeutic agents. PMID- 2215546 TI - Enhanced assays detect increased chromosome damage and sister-chromatid exchanges in heroin addicts. AB - To refine previous studies of chromosome damage (CD) and sister-chromatid exchanges (SCE) in heroin addicts, we applied new methods developed in our laboratory to enhance detection of the cytogenetic effects of low-level radiation exposure in hospital workers. For CD analysis, we applied our thymidine fluorodeoxyuridine-caffeine (TFC) enhancement procedure in which cells at setup receive 1 x 10(-7) M fluorodeoxyuridine to inhibit thymidylate synthetase and 4 X 10(-5) M thymidine to satisfy the induced requirement, and then in G2 receive 2.2 mM caffeine to modulate DNA repair. For SCE enhancement, caffeine treatment was initiated in G1 at 19 h before harvest. Using both standard and enhanced procedures for CD and SCE analysis, blood samples were evaluated from 20 street heroin addicts and 22 controls. Standard 2-day CD and 3-day SCE assays showed small, insignificant genotoxic increases in addicts while the enhanced CD and SCE assays showed highly significant increases. Most CD events were in the form of chromatid and chromosome breaks. There were no rings and only a few dicentrics were observed in the TFC-enhanced cultures. Although quadriradials are rare, 10 were found in addict TFC-cultures and 3 in control TFC-cultures. With the standard CD assay, the mean number of chromosome breaks per 100 cells was 0.727 for controls and 1.056 for addicts (not significant). With the TFC-enhanced assay, the same measure showed 1.483 chromosome breaks for controls and 5.143 for addicts (highly significant, ANOVA: p less than 0.0001). A highly significant difference was also observed for chromatid-type damage with the TFC-enhanced assay (chromatid breaks per 100 cells: 16.793 for controls; 48.191 for addicts). The SCE data also showed significant differences with the enhanced assay. Scoring 25 cells/condition, standard SCE cultures showed 10.892 SCE/cell for controls and 11.732 SCE/cell for addicts (not significant). With CAF enhancement there were 13.08 SCE/cell for controls and 17.05 SCE/cell for addicts (ANOVA: p less than 0.008). These findings indicate that detection of CD and SCE effects can be significantly enhanced by the use of these new procedures. The finding of greatly increased chromatid damage in the addicts with the TFC procedure suggests that at least part of the CD detected occurred in vitro and is not a product of prior in vivo damage. Therefore exposure to this drug and perhaps other environmental agents may not only leave a residue of DNA or chromosome damage but may also induce a sensitivity to further genotoxic damage that is revealed by using the enhanced procedures. PMID- 2215547 TI - Sensitive method for the detection of mutagenic nitroarenes and aromatic amines: new derivatives of Salmonella typhimurium tester strains possessing elevated O acetyltransferase levels. AB - Acetyl-CoA: N-hydroxyarylamine O-acetyltransferase is an enzyme involved in the intracellular metabolic activation of arylhydroxylamines derived from mutagenic nitroarenes and aromatic amines. The acetyltransferase gene of Salmonella typhimurium TA1538 was cloned into pBR322 and the plasmids harboring the gene were introduced into TA98 and TA100. The resulting strains (YG1024 and YG1029) had about 100 times higher 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d] imidazole (N-hydroxy-Glu-P-1) O-acetyltransferase activity than TA1538 containing pBR322, and were extremely sensitive to the mutagenic actions of 2-nitrofluorene, 1-nitropyrene, 1,8-dinitropyrene, 2-amino-6-methyldipyrido[1,2-a:3',2-d) imidazole (Glu-P-1), 2-aminofluorene and 2-aminoanthracene. These results indicate that the new strains permit the efficient detection of the mutagenicity of environmental nitroarenes and aromatic amines. PMID- 2215548 TI - The development of the U.S. EPA health effects research laboratory frozen blood cell repository program. AB - We have suggested that proper blood-cell freezing and storage is necessary in longitudinal studies with reduced between tests error, for specimen sharing between laboratories and for convenient scheduling of assays. Our present purpose is to describe the design and use of a prototype computer program, Cryovial, for data-based management of frozen cell repositories. We are pleased to provide, free of charge upon request, a 5.25" (specify 0.36 or 1.2 MB) disk containing all files required to run Cryovial. PMID- 2215549 TI - The International Association of Environmental Mutagen Societies (IAEMS). PMID- 2215550 TI - Ratio of acentrics to dicentrics in human lymphocytes exposed to X rays and misonidazole. AB - A 0.8 mM concentration of misonidazole was added to human blood samples before exposure to graded X-ray single doses, in order to investigate the dependence of the frequency ratio of acentrics to dicentrics, produced in lymphocytes, on treatment with radiation, the substance and the combination of the 2 agents. The results confirm the findings of a previous experiment carried out using sodium iothalamate, showing that this ratio is markedly influenced by the relative action of the physical and the chemical agents, especially at low radiation doses, because of the enhancement of the frequency of acentrics, and not of dicentrics, caused by the presence of the drug compared to the spontaneous level. PMID- 2215551 TI - Genotoxic effects of thiram evaluated by sister-chromatid exchanges in human lymphocytes. AB - The purpose of this investigation was to study the genotoxic potential of thiram (CAS No. 137-26-8) using an in vitro sister-chromatid exchange (SCE) assay with human lymphocytes. The results indicate that thiram and its metabolites increase the SCE frequencies 2-fold over those observed in the negative controls. The standard inducers cyclophosphamide and ethyl methanesulfonate increased SCE frequencies 10- and 4-fold, respectively, over untreated levels. PMID- 2215552 TI - Chromosomal aberrations, sister-chromatid exchanges, cell-cycle kinetics and satellite associations in human lymphocyte cultures exposed to vanadium pentoxide. AB - Treatment of human lymphocytes with vanadium pentoxide (V2O5) was not found to increase the frequency of structural chromosomal aberrations (CA) and sister chromatid exchanges (SCE). However, V2O5 significantly increased polyploid cell frequency; also, the mitotic index (MI) was significantly decreased, and the average generation time (AGT) was significantly increased. Finally, the frequency of cells with satellite associations (SA), the frequency of SA per cell, and the frequency of chromosomes associated increased in treated cultures. PMID- 2215553 TI - Preventive action of thioethers towards in vitro DNA binding and mutagenesis in E. coli K12 by alkylating agents. AB - Thioethers are effective scavengers of electrophilic metabolites derived from the hepatocarcinogen N-hydroxy-2-acetylaminofluorene (van den Goorbergh et al., 1987). In this study 2 of these thioethers, 4-(methylthio)benzoic acid (MTB) and its methylester, methyl 4-(methylthio)benzoate (MMTB), have been tested for their ability to prevent in vitro DNA binding and mutation induction in E. coli K12 by the direct alkylating agents ethylnitrosourea (ENU), methylnitrosourea (MNU), ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS). In addition to MTB and MMTB, the thioether L-methionine (Met), and the thiols glutathione (GSH) and L-cysteine (Cys) were included for reasons of comparison. MTB was able to (partially) prevent DNA binding and mutation induction by ENU. However, this thioether was ineffective with EMS. DNA binding and mutagenesis by EMS were (partially) prevented by GSH and Cys, while these thiols could not prevent DNA binding and mutation induction by ENU. MMTB was unable to prevent mutation induction by these ethylating agents. With the methylating agents, similar effects of MTB were observed: MTB effectively prevented mutation induction by MNU while it was much less effective towards MMS. GSH and Cys were comparably effective as antimutagenic agents towards both methylating agents. Met was unable to prevent either DNA binding or mutation induction by these agents. Taken together, the results show that aromatic thioethers are able to trap genotoxic electrophiles derived from the nitrosoureas ENU and MNU, and may therefore act as potential anticarcinogens towards these agents, which are only poorly detoxified by GSH. PMID- 2215554 TI - Unscheduled DNA synthesis in growing roots and stored embryos of Vicia faba after the action of maleic hydrazide and methyl methanesulphonate. AB - Growing roots of Vicia faba were treated with MH for 5 h, washed for 2 h and exposed to 3H-thymidine (3H-TdR) for additional 2-h periods at 7 h, 24 h and 32 h after the onset of MH treatment, to label DNA. As the replicative DNA synthesis was suppressed by HU, an enhancement of 3H-TdR incorporation into nuclear DNA above the control, as determined by microautoradiography, was considered to be due to unscheduled DNA synthesis induced by the mutagen. A significantly higher incorporation of 3H-TdR into DNA of MH-treated roots occurred, when labelling was applied 7 h after the MH action, whereas at 24 h only slight and at 32 h no enhancement of DNA labelling above control was registered. A 3-14-day storage with 50% water content of V. faba seeds exposed to MH or MMS resulted in a recovery from mutagen-induced chromosomal damage and a significantly higher incorporation of 3H-TdR into nuclear DNA. This supports the hypothesis that recovery from MH- and MMS-induced chromosomal damage is mediated by excision repair during seed storage. PMID- 2215555 TI - Sensitivity of Salmonella typhimurium YG1024 to urine mutagenicity caused by cigarette smoking. AB - Salmonella typhimurium YG1024, an O-acetyltransferase-overproducing derivative of TA98, was found to be more sensitive in detecting mutagenicity in human urine caused by cigarette smoking, than the conventional strain TA98, in Ames test in the presence of S9 mix. YG1021, another derivative of TA98 with elevated nitroreductase levels, did not show increased sensitivity. These results suggest that the mutagenic compounds concentrated by Blue Rayon from smokers' urine are aromatic amino compounds. PMID- 2215556 TI - Investigations on mutagenicity and genotoxicity of pentamidine and some related trypanocidal diamidines. AB - Pentamidine, DAPI and some related compounds (DAI, 6-Br-AI, DPTN, DIPI, 3-Am-DAI, DiaPBF) were investigated in 2 different screening test systems for their potential mutagenic and cytotoxic effects, in the light of their binding to DNA. In the Ames test using Salmonella typhimurium strains TA98 and TA100 with and without metabolic activation no mutagenic effects could be observed. All diamidines tested, except DAI, were toxic at concentrations of 0.5 and 1.0 mumole/plate. In the sister-chromatid exchange (SCE) assay with human peripheral lymphocytes all compounds tested were growth-retarding particularly in the G0 phase. A significant induction of SCEs could only be seen after treatment with the monoamidino compound 6-Br-AI at a concentration of 100 mumole/l. It is concluded from the data obtained that pentamidine and related diamidines in the 2 assays tested show no mutagenic or genotoxic effects, in spite of their tight binding to DNA. PMID- 2215557 TI - Antimutagenic action of cobaltous chloride on radiation-induced mutations in cultured Chinese hamster cells. AB - The effects of cobaltous chloride on 8-azaguanine (8AG)-resistant mutations induced by gamma-rays or ultraviolet (UV) light in cultured Chinese hamster V79 cells were examined. Cobaltous chloride alone had no significant effects on survival and mutations of V79 cells at concentrations less than 1 x 10(-5) M. Cobaltous chloride at a concentration of 3 x 10(-6) M had a marked effect in reducing 8AG-resistant mutations induced by gamma-rays of 2-6 Gy, when cells were incubated for 6-7 days in the presence of cobaltous chloride after gamma-ray irradiation (posttreatment). The pretreatment of cells with cobaltous chloride for 6 days before gamma-ray irradiation reduced 8AG-resistant mutations induced by gamma-rays. Pre- or post-treatment with cobaltous chloride had no such effect on UV-induced mutations, however. The difference in responsiveness to cobaltous chloride between bacterial and mammalian cell systems is discussed. PMID- 2215558 TI - Nurses have political clout: let's exercise it. PMID- 2215559 TI - Certification and you. PMID- 2215560 TI - Effect of long-term monitoring of glycosylated hemoglobin levels in insulin dependent diabetes mellitus. AB - BACKGROUND: The value of routine measurements of glycosylated hemoglobin (hemoglobin A1c) in the care of patients with diabetes mellitus is uncertain. We undertook this study to determine whether knowledge of hemoglobin A1c values would result in improved metabolic control in a group of patients with insulin dependent diabetes mellitus (IDDM). METHODS: We randomly assigned 240 patients with IDDM to one of two groups that were comparable in age, sex, duration of diabetes, and initial hemoglobin A1c levels. The patients were followed for a year, and the hemoglobin A1c concentration was measured at three-month intervals. The hemoglobin A1c values were used in assessing glycemic control and modifying therapy in one of the two groups. In the other, care givers were not aware of the hemoglobin A1c levels and relied on blood or urine glucose measurements to monitor treatment. RESULTS: Among the 222 patients still being followed after one year, the mean hemoglobin A1c value decreased significantly--from 10.1 to 9.5 percent (P less than 0.005)--in the group whose hemoglobin A1c level was monitored (n = 115), whereas the initial and one-year values in the control group (n = 107) were 10.0 and 10.1 percent, respectively. The proportion of patients with poor control, defined as those having a hemoglobin A1c value above 10.0 percent, decreased from 46 to 30 percent (P less than 0.01) in the group whose hemoglobin A1c level was monitored but did not change significantly (45 to 50 percent) in the control group. The patients in the group whose hemoglobin A1c level was monitored were seen and their insulin regimens changed more often, but they were hospitalized for acute care of their diabetes less often than those in the control group. A similar decrease in hemoglobin A1c values occurred in the control group in the following year, when their care givers knew their hemoglobin A1c values. CONCLUSIONS: Regular measurements of hemoglobin A1c lead to changes in diabetes treatment and improvement of metabolic control, indicated by a lowering of hemoglobin A1c values. PMID- 2215561 TI - Coffee, caffeine, and cardiovascular disease in men. AB - BACKGROUND: For many years, an association between coffee consumption and the risk of coronary heart disease has been suspected. Although based on small numbers of end points, a prospective study has suggested a particularly strong association between recent coffee drinking and the incidence of cardiovascular disease. METHODS: We examined prospectively the relation of coffee consumption with the risk of myocardial infarction, need for coronary-artery bypass grafting or angioplasty, and risk of stroke in a cohort of 45,589 U.S. men who were 40 to 75 years old in 1986 and who had no history of cardiovascular disease. RESULTS: During two years of follow-up observation, 221 participants had a nonfatal myocardial infarction or died of coronary heart disease, 136 underwent coronary artery surgery or angioplasty, and 54 had a stroke. Total coffee consumption was not associated with an increased risk of coronary heart disease or stroke. The age-adjusted relative risk for all cardiovascular disease among participants who drank four or more cups of coffee per day was 1.04 (95 percent confidence intervals, 0.74 to 1.46). Increasing levels of consumption of caffeinated coffee were not associated with higher risks of cardiovascular disease. Higher consumption of decaffeinated coffee, however, was associated with a marginally significant increase in the risk of coronary heart disease (relative risk, 1.63; 95 percent confidence interval, 1.02 to 2.60). Finally, we observed no pattern of increased risk across the subgroups of participants with increasing intakes of caffeine from all sources. Adjustment for major cardiovascular-risk indicators, dietary intake of fats, and cholesterol intake did not materially alter these associations. CONCLUSIONS: These findings do not support the hypothesis that coffee or caffeine consumption increases the risk of coronary heart disease or stroke. PMID- 2215562 TI - Eosinophilic inflammation in asthma. AB - BACKGROUND AND METHODS: The importance of eosinophils in the pathogenesis of bronchial asthma is not established. In an attempt to evaluate the role of eosinophilic inflammation in asthma, we compared 10 normal subjects with 43 patients with chronic asthma, 19 of whom had severe disease as assessed by a clinical scoring method described by Aas and by pulmonary-function tests. Eosinophils were counted in peripheral blood and bronchoalveolar-lavage fluid, and in biopsy specimens obtained from the patients and post mortem from 8 subjects without asthma, but not from the 10 normal controls. Eosinophil cationic protein was titrated by radioimmunoassay in the bronchoalveolar-lavage fluid from all subjects and studied by immunohistochemistry in the biopsy specimens. RESULTS: There was a significant increase in the number of peripheral-blood eosinophils in the patients that was correlated with the clinical severity of asthma (P less than 0.001) and pulmonary function (P less than 0.03). Levels of eosinophils and eosinophil cationic protein were increased in the bronchoalveolar lavage fluid from the patients and were also correlated with the severity of asthma (P less than 0.001 and P less than 0.002, respectively). Hematoxylin-eosin staining of bronchial-biopsy specimens showed that intraepithelial eosinophils were present only in patients with asthma. Immunohistochemical analysis of eosinophil cationic protein revealed that normal subjects had only a few nondegranulated eosinophils deep in the submucosa, whereas all the patients had degranulated eosinophils beneath the basement membrane and among epithelial cells. In some patients there was a relation between the presence of degranulated eosinophils and epithelial damage. CONCLUSIONS: Eosinophilic inflammation of the airways is correlated with the severity of asthma. These cells are likely to play a part in the epithelial damage seen in this disease. PMID- 2215563 TI - Outcomes of pregnancy in a national sample of resident physicians. AB - BACKGROUND: Physically demanding, highly stressful work during pregnancy has been reported to cause a variety of adverse outcomes. It has been difficult, however, to separate the effects of work from those of socioeconomic status. METHODS: By means of a national questionnaire-based survey, we studied the outcomes of pregnancy during residency for 4412 women who graduated from medical school in 1985 and for the wives of 4236 of their male classmates, who served as controls. RESULTS: The rate of response to our survey was 87 percent (4412 of 5079) for the women residents and 85 percent (4236 of 4968) for the wives of the male residents. There were no significant differences in the proportion of pregnancies ending in miscarriage (13.8 percent for residents vs. 11.8 percent for their classmates' wives, P = 0.12), ectopic gestations (0.5 percent vs. 0.8 percent, P = 0.69), and stillbirths (0.2 percent vs. 0.5 percent, P = 0.20). There were 989 women residents and 1238 residents' wives whose first pregnancy during residency resulted in the live birth of a singleton infant. Although during each trimester the women residents worked many more hours than the wives of the male residents, the frequency of preterm births (less than 37 weeks' gestation) was similar: 6.5 percent for residents and 6.0 percent for residents' wives (odds ratio = 1.1; 95 percent confidence interval, 0.7 to 1.5). Infants who were small for gestational age (with birth weights less than the 10th percentile for gestational age) were born to 5.3 percent of the residents and 5.8 percent of the residents' wives (odds ratio = 0.9; 95 percent confidence interval, 0.6 to 1.3). Adjustment for factors that differed between the women residents and the wives of male residents resulted in odds ratios of 1.2 (95 percent confidence interval, 0.8 to 1.7) for preterm delivery and 0.9 (95 percent confidence interval, 0.6 to 1.3) for the delivery of an infant who was small for gestational age. However, the women residents more frequently reported having had preterm labor (11 percent vs. 6 percent), but not preterm delivery (6.5 percent vs. 6.0 percent); preeclampsia was also more common among the women residents (8.8 percent vs. 3.5 percent). CONCLUSIONS: These results suggest that working long hours in a stressful occupation has little effect on the outcome of pregnancy in an otherwise healthy population of high socioeconomic status. PMID- 2215564 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 41-1990. A 66-year-old woman with rapidly deteriorating renal function. PMID- 2215565 TI - Hemoglobin Alc--infatuation or the real thing? PMID- 2215566 TI - Why can't a woman be more like a man? PMID- 2215567 TI - Heritability of weight gain and obesity. PMID- 2215568 TI - Erythropoietin for zidovudine-induced anemia. PMID- 2215569 TI - Beta 2-microglobulin amyloidosis in chronic renal failure. PMID- 2215570 TI - Illicit drug and alcohol use during pregnancy. PMID- 2215571 TI - Anaphylactic reaction to "Heartwise". PMID- 2215572 TI - Informing physicians of charges for tests. PMID- 2215573 TI - Thoughts as I watched the Peabody Building fall, March 31, 1990. PMID- 2215574 TI - Experiences with conversion to Systeme international units. PMID- 2215575 TI - The diagnosis and prognosis of autosomal dominant polycystic kidney disease. AB - BACKGROUND: Autosomal dominant polycystic kidney disease is usually caused by a mutant gene at the PKD1 locus on the short arm of chromosome 16, but in about 4 percent of families with the disorder it is caused by unknown mutations elsewhere in the genome. The natural course of the disease in both genetic forms is not well characterized. METHODS: We studied 17 families with autosomal dominant polycystic kidney disease to compare presymptomatic diagnosis by ultrasonography with diagnosis by genetic-linkage studies and to relate clinical variation of the disease to whether the PKD1 mutation was implicated. RESULTS: In 10 families the disorder was found to cosegregate with polymorphic DNA markers flanking the PKD1 locus, in 2 families it did not, and in 5 families linkage could not be determined. In the 10 families with the PKD1 mutation, 46 percent of the members less than 30 years old who had a 50 percent risk of inheriting a mutation had renal cysts, as compared with 11 percent of the members of the two families without linkage (P less than 0.001). In the PKD1 families, all 67 diagnoses made by ultrasonography were confirmed by determination of the genotype as inferred from linkage. Forty of 48 members (83 percent) less than 30 years old who inherited the PKD1 mutation had renal cysts. All 27 members 30 years old or older who inherited the mutation had renal cysts, suggesting that the probability of a false negative diagnosis did not exceed 0.13 in this age group (P less than 0.05). The mean (+/- SE) age at the onset of end-stage renal disease among members of the PKD1 families was 56.7 +/- 1.9 years, as compared with 69.4 +/- 1.7 years among members with cysts in the families without linkage (P = 0.0025). Hypertension and renal impairment were less frequent and occurred later in the families without the PKD1 mutation. CONCLUSIONS: At present, in most persons with a 50 percent risk of autosomal dominant polycystic kidney disease, imaging techniques are the only mode of reaching a diagnosis before symptoms appear. In such persons a negative ultrasonographic study during early adult life indicates that the likelihood of inheriting a PKD1 mutation is small. In the few who inherit a non-PKD1 mutation for polycystic kidney disease, renal failure is likely to occur relatively late in life. PMID- 2215576 TI - The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease. AB - BACKGROUND: A high incidence of hypertension (50 to 75 percent) occurs early in the course of autosomal dominant polycystic kidney disease. Cyst enlargement, causing bilateral renal ischemia and subsequent release of renin, is proposed as the cause of this form of hypertension. METHODS: To investigate this hypothesis, we measured plasma renin activity and aldosterone concentrations during short term and long-term converting-enzyme inhibition in 14 patients with hypertension due to polycystic kidney disease, 9 patients with essential hypertension, 11 normotensive patients with polycystic kidney disease, and 13 normal subjects. The groups were comparable with respect to age, sex, body-surface area, degree of hypertension, sodium excretion, and renal function. RESULTS: During the short term study, the mean (+/- SE) plasma renin activity was significantly higher in the hypertensive patients with polycystic kidney disease than in the patients with essential hypertension, in the supine (0.36 +/- 0.06 vs. 0.22 +/- 0.06 ng per liter.second, P = 0.05) and upright positions (1.03 +/- 0.14 vs. 0.61 +/- 0.08 ng per liter.second, P less than 0.03) and after converting-enzyme inhibition (1.97 +/- 0.28 vs. 0.67 +/- 0.17 ng per liter.second, P less than 0.0006). The mean arterial pressures measured in the supine and upright positions and the plasma aldosterone concentrations measured in the upright position were significantly higher in the normotensive patients with polycystic kidney disease than in the normal subjects. After six weeks of converting-enzyme inhibition, renal plasma flow increased (P less than 0.005), and both renal vascular resistance (P less than 0.007) and the filtration fraction (P less than 0.02) decreased significantly in the hypertensive patients with polycystic kidney disease but not in the patients with essential hypertension. CONCLUSIONS: The renin-angiotensin-aldosterone system is stimulated significantly more in hypertensive patients with polycystic kidney disease than in comparable patients with essential hypertension. The increased renin release, perhaps due to renal ischemia caused by cyst expansion, probably contributes to the early development of hypertension in polycystic kidney disease. PMID- 2215577 TI - Mercury exposure from interior latex paint. AB - BACKGROUND: Many paint companies have used phenylmercuric acetate as a preservative to prolong the shelf life of interior latex paint. In August 1989, acrodynia, a form of mercury poisoning, occurred in a child exposed to paint fumes in a home recently painted with a brand containing 4.7 mmol of mercury per liter (at that time the Environmental Protection Agency's recommended limit was 1.5 mmol or less per liter). METHODS: To determine whether the recent use of that brand of paint containing phenylmercuric acetate was associated with elevated indoor-air and urinary mercury concentrations, we studied 74 "exposed" persons living in 19 homes recently painted with the brand and 28 "unexposed" persons living in 10 homes not recently painted with paint containing mercury. RESULTS: The paint samples from the homes of exposed persons contained a median of 3.8 mmol of mercury per liter, and air samples from the homes had a median mercury content of 10.0 nmol per cubic meter (range, less than 0.5 to 49.9). No mercury was detected in paint or air samples from the homes of unexposed persons. The median urinary mercury concentration was higher in the exposed persons (4.7 nmol of mercury per millimole of creatinine; range, 1.4 to 66.5) than in the unexposed persons (1.1 nmol per millimole; range, 0.02 to 3.9; P less than 0.001). Urinary mercury concentrations within the range that we found in exposed persons have been associated with symptomatic mercury poisoning. CONCLUSIONS: We found that potentially hazardous exposure to mercury had occurred among persons whose homes were painted with a brand of paint containing mercury at concentrations approximately 2 1/2 times the Environmental Protection Agency's recommended limit. PMID- 2215578 TI - Plasma prorenin activity and complications in children with insulin-dependent diabetes mellitus. AB - BACKGROUND: Renin, secreted into the blood by the juxtaglomerular cells of the kidneys, is derived from a larger precursor, prorenin. Plasma prorenin activity is increased in patients with insulin-dependent (Type I) diabetes mellitus who have microvascular complications of their disease. We undertook this study to determine prospectively whether rising prorenin activity can predict the development of complications in young patients with Type I diabetes. METHODS AND RESULTS: Plasma prorenin was measured in 135 children and adolescents with Type I diabetes. The mean (+/- SE) plasma prorenin activity among the 32 patients over the age of 10 years who had had uncomplicated diabetes for 0.1 to 5 years was 8.43 +/- 0.58 ng of angiotensin I per liter.second, as compared with 7.06 +/- 0.32 in 37 control subjects of the same age (P less than 0.05). In the 9 patients older than 10 who had retinopathy or overt albuminuria, the mean plasma prorenin activity was 13.09 +/- 1.43 ng of angiotensin I per liter.second (P less than 0.0001). In 34 patients 10 years old or older with uncomplicated diabetes, 3 to 13 measurements of plasma prorenin activity were taken during a follow-up period of 6 to 39 months. Urinary albumin was determined at each visit, and the patients had regular retinal examinations. Only 1 of the 20 patients who had consistently normal plasma prorenin values had overt albuminuria (ratio of urinary albumin to creatinine, greater than 0.017) or retinopathy, whereas one or both of these complications appeared in 8 of the 14 who had at least one high prorenin value. The plasma prorenin value was significantly higher in these eight patients at least 18 months before a complication was found. CONCLUSIONS: Increased plasma prorenin activity identifies a group of young patients with diabetes who are at high risk for retinopathy or nephropathy. PMID- 2215579 TI - The value of lowering cholesterol after myocardial infarction. PMID- 2215580 TI - Lassa fever in the United States. Investigation of a case and new guidelines for management. PMID- 2215581 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 42-1990. A previously healthy 41-year-old man with meningoencephalitis and the rapid development of coma. PMID- 2215582 TI - Renin--from beginning to end. PMID- 2215583 TI - Mercury--an element of mystery. PMID- 2215584 TI - Imported Lassa fever--reexamining the algorithms. PMID- 2215585 TI - Sexually transmitted diseases and rape. PMID- 2215586 TI - Short-term reductions in serum lipids through diet and exercise. PMID- 2215587 TI - Obesity and risk of coronary heart disease in women. PMID- 2215588 TI - Growth of African Pygmies in early childhood. PMID- 2215589 TI - Acute fatal leukoencephalopathy after interleukin-2 therapy. PMID- 2215590 TI - Myocardial infarction after inhalation of methamphetamine. PMID- 2215591 TI - The case of Baby L. PMID- 2215592 TI - Pregnancy potential of human oocytes--the effect of cryopreservation. AB - BACKGROUND: In vitro fertilization, sometimes involving the cryopreservation of human embryos, has become a routine procedure for the treatment of infertility. Even though there are embryos available for transfer in about 85 percent of the treatment cycles, the rate of pregnancy rarely exceeds 25 percent per cycle. We designed this study to investigate two questions: Does this high rate of failure result from inadequate technique, or does it simply reflect the maximal potential of a cohort of aspirated eggs to produce a pregnancy? And to what extent does cryopreservation affect the capacity for implantation of embryos? METHODS: The study was conducted among patients enrolled in an egg-donation program. Aspirated eggs from a given cohort were distributed to the donor herself and a few recipients. The recipients were prepared by a standard protocol of hormone replacement and were assigned at random to the transfer of either fresh or frozen and thawed embryos. The donors received only fresh embryos. RESULTS: Forty cycles of donation were studied. In 25 cycles (63 percent) pregnancy was established in the donor, in the recipient (or recipients), or in both. Of the fresh embryos that were transferred to the recipients, 24 percent were successfully implanted, as compared with only 7.7 percent of the frozen and thawed embryos (P less than 0.01). A pregnancy success rate of 37 percent per recipient cycle was observed in the recipients of fresh embryos, as compared with a rate of only 16 percent in those receiving frozen and thawed embryos (P less than 0.05). CONCLUSIONS: The majority of egg cohorts evidently possess the potential to produce a pregnancy, but cryopreservation of human embryos significantly reduces their capacity for implantation. PMID- 2215593 TI - The epidemiology and clinical aspects of the hemolytic uremic syndrome in Minnesota. AB - BACKGROUND: The frequency of the hemolytic uremic syndrome, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, is increasing. Although Escherichia coli serotype O157:H7 has been implicated as a causative agent, more information is needed about the basic epidemiology and clinical aspects of this syndrome. METHODS: We conducted a retrospective population-based study of hemolytic uremic syndrome in Minnesota residents less than 18 years of age from 1979 through 1988 to assess trends in disease occurrence, describe the clinical illness, and identify predictors of disease severity and outcome. We also conducted a case-control study of patients with onsets of illness from 1986 through 1988 to examine risk factors. RESULTS: One hundred seventeen patients were identified. The mean annual incidence increased from 0.5 case per 100,000 child-years among children less than 18 in 1979 (6 cases) to 2.0 cases per 100,000 in 1988 (26 cases) (P = 0.000004). E. coli O157:H7 was isolated from 13 of 28 patients (46 percent) who had stool specimens submitted for testing. For those who presented with typical hemolytic uremic syndrome, an elevated polymorphonuclear-leukocyte count on hospital admission, a shorter duration of prodrome, and the presence of bloody diarrhea were predictive of severe disease. In the case-control study, the patients were more likely to attend large daycare centers (more than 50 children) than were the controls (odds ratio, 10.2; P = 0.03), suggesting that day-care attendance may be a risk factor. On the basis of the population-attributable risk, however, this factor could account for no more than 16 percent of the cases. CONCLUSIONS: This study provides evidence for an increase in the incidence of hemolytic uremic syndrome, which is probably related to an increased incidence of E. coli O157:H7 infections. Hemolytic uremic syndrome has become an important pediatric and public health problem. PMID- 2215594 TI - A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes. AB - BACKGROUND: The presence of cytoplasmic islet-cell autoantibodies has been recognized as a risk factor for the development of diabetes mellitus in relatives of patients with insulin-dependent diabetes mellitus (IDDM), but the magnitude of the risk is unknown, as is the influence of other factors, such as age, sex, and race. METHODS: From 1979 through 1989, we studied 4015 initially nondiabetic relatives of 1590 probands with IDDM to determine the risk of IDDM according to the presence and titer of autoantibodies, as well as other factors. RESULTS: Of the 4015 nondiabetic relatives, 125 (3.1 percent) had islet-cell antibodies in their initial serum samples, and 40 contracted IDDM. Islet-cell antibodies were most frequent (4.3 percent) in relatives who were under 20 years of age (P = 0.001) and in those (4.8 percent) from families with more than one affected member (a multiplex pedigree) (P = 0.003). Independent risk factors for the development of diabetes in the relatives included age of less than 10 years at the time of the initial study (P = 0.001), membership in a multiplex pedigree (P = 0.02), and a positive test for islet-cell antibodies in the initial serum sample (P = 0.0001). Twenty-seven of the relatives in whom diabetes developed (67.5 percent) had positive tests for islet-cell antibodies before the diagnosis of IDDM, giving a relative risk of IDDM of 68 (95 percent confidence interval, 34 to 134) for antibody-positive relatives. Islet-cell-antibody titers of 20 Juvenile Diabetes Foundation units or higher were associated with an increasing risk of diabetes. CONCLUSIONS: Nondiabetic relatives of probands with IDDM who are in the first two decades of life, are members of multiplex pedigrees, and have increased titers of islet-cell antibodies are the most likely to contract IDDM themselves. PMID- 2215595 TI - Predicting the appropriate use of carotid endarterectomy, upper gastrointestinal endoscopy, and coronary angiography. AB - BACKGROUND AND METHODS: In a nationally representative population 65 years of age or older, we have demonstrated that about one quarter of coronary angiographies and upper gastrointestinal endoscopies and two thirds of carotid endarterectomies were performed for reasons that were less than medically appropriate. In this paper we examine whether specific characteristics of patients (age, sex, and race), physicians (age, board-certification status, and experience with the procedure), or hospitals (teaching status, profit-making status, and size) predict whether a procedure will be performed appropriately. RESULTS: In general, we found that little of the variability in the appropriateness of care (4 percent or less) could be explained on the basis of standard, easily obtainable data about the patient, the physician, or the hospital. For all three procedures, however, performance in a teaching hospital increased the likelihood that the reasons would be medically appropriate (P = 0.09 for angiography, P = 0.30 for endoscopy, and P less than 0.01 for endarterectomy). In addition, angiographies were more often performed for appropriate reasons in older or more affluent patients (P less than 0.01 for both). Being treated by a surgeon who performed a high rather than a low number of procedures decreased the likelihood of an appropriate endarterectomy by one third, from 40 to 28 percent (P less than 0.01). CONCLUSIONS: Appropriateness of care cannot be closely predicted from many easily determined characteristics of patients, physicians, or hospitals. Thus, for the present, if appropriateness is to be improved it will have to be assessed directly at the level of each patient, hospital, and physician. PMID- 2215596 TI - Treatment of hypertensive crisis. PMID- 2215597 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1990. A 3 1/2-year-old boy with pharyngitis, fever, rash, and prominent cervical lymphadenopathy. PMID- 2215598 TI - Outcomes research, cost containment, and the fear of health care rationing. PMID- 2215599 TI - Neonatal circumcision. PMID- 2215600 TI - T-cell receptors in ataxia-telangiectasia. PMID- 2215601 TI - Case 51-1989: the tamoxifen advantage. PMID- 2215602 TI - Microwave popcorn--ocular injury caused by steam. PMID- 2215603 TI - Miliary tuberculosis after extracorporeal shock-wave lithotripsy. PMID- 2215604 TI - A proposal to provide health insurance to all children and all pregnant women. PMID- 2215605 TI - Spinal bone loss and ovulatory disturbances. AB - BACKGROUND: Osteoporosis develops in women with estrogen deficiency and amenorrhea who lose bone at an accelerated rate. It is not known to what extent bone loss differs between ovulatory women with regular menstrual cycles who are training intensely and those who are sedentary. METHODS: We measured the density of cancellous spinal bone from the 12th thoracic vertebra to the 3rd lumbar vertebra by quantitative computed tomography on two occasions one year apart in 66 premenopausal women 21 to 42 years of age. All the women had two consecutive ovulatory cycles immediately before entering the study. Twenty-one women were training for a marathon, 22 ran regularly but less intensively, and 23 had normal levels of activity. The lengths of the women's menstrual cycles and luteal phases, diet, exercise levels, and hormonal levels were also determined. We defined ovulatory disturbances as anovulatory cycles and cycles with short luteal phases. RESULTS: The mean (+/- SD) spinal bone density in the 66 women decreased 3.0 +/- 4.8 mg per cubic centimeter per year (2.0 percent per year) (P less than 0.001). Amenorrhea did not develop in any woman during the year of observation (only 2.7 percent of the cycles were greater than 36 days long). Ovulatory disturbances occurred in 29 percent of all cycles, however. Bone loss was strongly associated with these disturbances (r = 0.54, 24 percent of the variance). The 13 women who had anovulatory cycles lost bone mineral at a rate of 6.4 +/- 3.8 mg per cubic centimeter per year (4.2 percent per year). The women training for a marathon had menstrual cycles similar to those of the women in the other two groups. CONCLUSION: Decreases in spinal bone density among women with differing exercise habits correlated with asymptomatic disturbances of ovulation (without amenorrhea) and not with physical activity. PMID- 2215606 TI - Ulcerative colitis and colorectal cancer. A population-based study. AB - BACKGROUND: The risk of colorectal cancer is increased among patients with ulcerative colitis. The magnitude of this increase in risk and the effects of the length of follow-up, the extent of disease at diagnosis, and age at diagnosis vary substantially in different studies. METHODS: To provide accurate estimates of the risk of colorectal cancer among patients with ulcerative colitis, we studied a population-based cohort of 3117 patients given a diagnosis of ulcerative colitis from 1922 through 1983 who were followed up through 1984. RESULTS: Ninety-two cases of colorectal cancer occurred in 91 patients. As compared with the expected incidence, the incidence of colorectal cancer in the cohort was increased (standardized incidence ratio [ratio of observed to expected cases] = 5.7; 95 percent confidence interval, 4.6 to 7.0). Less extensive disease at diagnosis was associated with a lower risk; for patients with ulcerative proctitis, the standardized incidence ratio was 1.7 (95 percent confidence interval, 0.8 to 3.2); for those with left-sided colitis, 2.8 (95 percent confidence interval, 1.6 to 4.4); and for those with pancolitis (extensive colitis, or inflammation of the entire colon), 14.8 (95 percent confidence interval, 11.4 to 18.9). Age at diagnosis and the extent of disease at diagnosis were strong and independent risk factors for colorectal cancer. For each increase in age group at diagnosis (less than 15 years, 15 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, and greater than or equal to 60 years), the relative risk of colorectal cancer, adjusted for the extent of disease at diagnosis, decreased by about half (adjusted standardized incidence ratio = 0.51; 95 percent confidence interval, 0.46 to 0.56). The absolute risk of colorectal cancer 35 years after diagnosis was 30 percent for patients with pancolitis at diagnosis and 40 percent for those given this diagnosis at less than 15 years of age. CONCLUSIONS: Close surveillance and perhaps even prophylactic proctocolectomy should be recommended for patients given a diagnosis of pancolitis, especially those who are less than 15 years of age at diagnosis. PMID- 2215607 TI - Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. AB - BACKGROUND AND METHODS: The plasma cholesteryl-ester transfer protein (CETP) catalyzes the transfer of cholesteryl esters from high-density lipoprotein (HDL) to other lipoproteins. We recently described a Japanese family with increased HDL levels and CETP deficiency due to a splicing defect of the CETP gene. To assess the frequency and phenotype of this condition, we screened 11 additional families with high HDL levels by means of a radioimmunoassay for CETP and DNA analysis. RESULTS: We found the same CETP gene mutation in four families from three different regions of Japan. Analysis of restriction-fragment-length polymorphisms of the mutant CETP allele showed that all probands were homozygous for the identical haplotype. Family members homozygous for CETP deficiency (n = 10) had moderate hypercholesterolemia (mean total cholesterol level [+/- SD], 7.01 +/- 0.83 mmol per liter), markedly increased levels of HDL cholesterol (4.24 +/- 1.01 mmol per liter) and apolipoprotein A-I, and decreased levels of low-density lipoprotein cholesterol (1.99 +/- 0.80 mmol per liter) and apolipoprotein B. Members heterozygous for the deficiency (n = 20), whose CETP levels were in the lower part of the normal range, had moderately increased levels of HDL cholesterol and apolipoprotein A-I and an increased ratio of HDL subclass 2 to HDL subclass 3, as compared with unaffected family members (1.5 +/- 0.8 vs. 0.7 +/- 0.4). CETP deficiency was not found in six unrelated subjects with elevated HDL cholesterol levels who were from different parts of the United States. CONCLUSIONS: CETP deficiency appears to be a frequent cause of increased HDL levels in the population of Japan, possibly because of a founder effect. The results that we observed in heterozygotes suggest that CETP normally plays a part in the regulation of levels of HDL subclass 2. There was no evidence of premature atherosclerosis in the families with CETP deficiency. In fact, the lipoprotein profile of persons with CETP deficiency is potentially antiatherogenic and may be associated with an increased life span. PMID- 2215608 TI - The effect of ursodiol on the efficacy and safety of extracorporeal shock-wave lithotripsy of gallstones. The Dornier National Biliary Lithotripsy Study. AB - BACKGROUND: In the treatment of gallstones with extracorporeal shock-wave lithotripsy, the bile acid ursodiol is administered to dissolve the gallstone fragments. We designed our study to determine the value of administering this agent. METHODS: At 10 centers, 600 symptomatic patients with three or fewer radiolucent gallstones 5 to 30 mm in diameter, as visualized by oral cholecystography, were randomly assigned to receive ursodiol or placebo for six months, starting one week before lithotripsy. RESULTS: The stones were fragmented in 97 percent of all patients, and the fragments were less than or equal to 5 mm in diameter in 46.8 percent. On the basis of an intention-to-treat analysis of all 600 patients, 21 percent receiving ursodiol and 9 percent receiving placebo (P less than 0.0001) had gallbladders that were free of stones after six months. Among those with completely radiolucent solitary stones less than 20 mm in diameter, 35 percent of the patients receiving ursodiol and 18 percent of those receiving placebo (P less than 0.001) were free of stones after six months. Biliary pain, usually mild, occurred in 73 percent of all patients but in only 13 percent of those who were free of stones after three and six months (P less than 0.01). There were few adverse events. Only diarrhea occurred with a significantly different frequency in the two groups: 32.6 percent were affected in the ursodiol group, as compared with 24.7 percent in the placebo group (P less than 0.04). Severe biliary pain occurred in 1.5 percent of all patients, acute cholecystitis in 1.0 percent, and acute pancreatitis in 1.5 percent; endoscopic sphincterotomy was performed in 0.5 percent, and cholecystectomy in 2.5 percent. CONCLUSIONS: Extracorporeal shock-wave lithotripsy with ursodiol was more effective than lithotripsy alone for the treatment of symptomatic gallstones, and equally safe. Treatment was more effective for solitary than multiple stones, radiolucent than slightly calcified stones, and smaller than larger stones. PMID- 2215609 TI - Lymphangioleiomyomatosis. Clinical course in 32 patients. PMID- 2215610 TI - Premenopausal bone loss--a risk factor for osteoporosis. PMID- 2215611 TI - Repair in utero of a fetal diaphragmatic hernia. PMID- 2215612 TI - Location of met locus on chromosome 7--a correction. PMID- 2215613 TI - Effect on physician-scientists of the low funding rate of NIH grant applications. PMID- 2215614 TI - Forgiveness of coinsurance. PMID- 2215615 TI - Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. AB - BACKGROUND AND METHODS: The effect of intensive lipid-lowering therapy on coronary atherosclerosis among men at high risk for cardiovascular events was assessed by quantitative arteriography. Of 146 men no more than 62 years of age who had apolipoprotein B levels greater than or equal to 125 mg per deciliter, documented coronary artery disease, and a family history of vascular disease, 120 completed the 2 1/2-year double-blind study, which included arteriography at base line and after treatment. Patients were given dietary counseling and were randomly assigned to one of three treatments: lovastatin (20 mg twice a day) and colestipol (10 g three times a day); niacin (1 g four times a day) and colestipol (10 g three times a day); or conventional therapy with placebo (or colestipol if the low-density lipoprotein [LDL] cholesterol level was elevated). RESULTS: The levels of LDL and high-density lipoprotein (HDL) cholesterol changed only slightly in the conventional-therapy group (mean changes, -7 and +5 percent, respectively), but more substantially among patients treated with lovastatin and colestipol (-46 and +15 percent) or niacin and colestipol (-32 and +43 percent). In the conventional-therapy group, 46 percent of the patients had definite lesion progression (and no regression) in at least one of nine proximal coronary segments; regression was the only change in 11 percent. By comparison, progression (as the only change) was less frequent among patients who received lovastatin and colestipol (21 percent) and those who received niacin and colestipol (25 percent), and regression was more frequent (lovastatin and colestipol, 32 percent; niacin and colestipol, 39 percent; P less than 0.005). Multivariate analysis indicated that a reduction in the level of apolipoprotein B (or LDL cholesterol) and in systolic blood pressure, and an increase in HDL cholesterol correlated independently with regression of coronary lesions. Clinical events (death, myocardial infarction, or revascularization for worsening symptoms) occurred in 10 of 52 patients assigned to conventional therapy, as compared with 3 of 46 assigned to receive lovastatin and colestipol and 2 of 48 assigned to receive niacin and colestipol (relative risk of an event during intensive treatment, 0.27; 95 percent confidence interval, 0.10 to 0.77). CONCLUSIONS: In men with coronary artery disease who were at high risk for cardiovascular events, intensive lipid-lowering therapy reduced the frequency of progression of coronary lesions, increased the frequency of regression, and reduced the incidence of cardiovascular events. PMID- 2215616 TI - Congenital syphilis presenting in infants after the newborn period. AB - BACKGROUND AND METHODS: There has been a recent, dramatic increase in the incidence of congenital syphilis, particularly in urban areas. We describe seven infants seen during one year who were first given a diagnosis of congenital syphilis at 3 to 14 weeks of age, when symptoms developed. We reviewed these infants' charts in order to ascertain the reasons for the failure to diagnose syphilis at birth and to identify the signs and symptoms of congenital syphilis in this group of infants. RESULTS: At delivery, four of the infants and their mothers had negative qualitative rapid-plasma-reagin tests for syphilis. The other three mothers had been seronegative during the pregnancy and were therefore not tested at delivery; two of their infants were seronegative at birth, and one was not tested. When the infants became symptomatic between 3 and 14 weeks of age and were admitted to the hospital, all seven infants and the five mothers available for testing were found to be seropositive for syphilis. Four infants presented with a characteristic diffuse rash; the other three presented with fever and were found on admission to have aseptic meningitis. All these infants had multisystem disease, as evidenced by hepatomegaly, increased aminotransferase and alkaline phosphatase levels, anemia, and monocytosis. In all the infants syphilis responded to parenteral penicillin. CONCLUSIONS: Congenital syphilis may be missed if serologic tests are not performed for both the mother and her infant at the time of delivery. Even when these tests are performed, some infants are not identified as having syphilis, probably because the infection is very recent and there has been insufficient time for an antibody response to develop. Some infants with congenital syphilis of later onset do not present with a typical rash; therefore, at least in areas where the disease is prevalent, serologic tests for syphilis should be included in the evaluation of all febrile infants, even those with negative results on serologic testing at birth. PMID- 2215617 TI - Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. AB - BACKGROUND: Night blindness is an early symptom of retinitis pigmentosa. The rod photoreceptors are responsible for night vision and use rhodopsin as the photosensitive pigment. METHODS AND RESULTS: We found three mutations in the human rhodopsin gene; each occurred exclusively in the affected members of some families with autosomal dominant retinitis pigmentosa. Two mutations were C-to-T transitions involving separate nucleotides of codon 347; the third was a C-to-G transversion in codon 58. Each mutation corresponded to a change in one amino acid residue in the rhodopsin molecule. None of these mutations were found in 106 unrelated normal subjects who served as controls. When the incidence of these three mutations was added to that of a previously reported mutation involving codon 23, 27 of 150 unrelated patients with autosomal dominant retinitis pigmentosa (18 percent) were found to carry one of these four defects in the rhodopsin gene. All 27 patients had abnormal rod function on monitoring of their electroretinograms. It appears that patients with the mutation involving codon 23 probably descend from a single ancestor. CONCLUSIONS: In some patients with autosomal dominant retinitis pigmentosa, the disease is caused by one of a variety of mutations of the rhodopsin gene. PMID- 2215618 TI - Hypercalcemia and ectopic secretion of parathyroid hormone by an ovarian carcinoma with rearrangement of the gene for parathyroid hormone. PMID- 2215619 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 45-1990. A 68-year-old man with recurrent hemoptysis and a pulmonary cavity containing a mass. PMID- 2215620 TI - Regression of coronary atherosclerosis. PMID- 2215621 TI - Congenital syphilis--breaking through the safety net. PMID- 2215622 TI - Design considerations for AIDS trials. PMID- 2215623 TI - Prognostic indicators in node-negative breast cancer. PMID- 2215624 TI - HLA-A11-associated resistance to skin cancer in renal-transplant recipients. PMID- 2215625 TI - Effect of tumor necrosis factor in normal subjects. PMID- 2215626 TI - Cyclosporine in primary biliary cirrhosis. PMID- 2215627 TI - Allopurinol-induced orotidinuria. PMID- 2215628 TI - Aminoaciduria due to vinyl-GABA administration. PMID- 2215629 TI - Competent patients and irrational choices. PMID- 2215630 TI - Editorial review of protocols for clinical trials. PMID- 2215631 TI - Our patient earth. PMID- 2215632 TI - Occupational exposure to HIV among house staff. PMID- 2215633 TI - Name changes in fungi of microbiological, industrial and medical importance. Part 4. AB - This is the fourth in a series of reports bringing changes in the names of fungi of microbiological, industrial and medical importance to the attention of workers in these fields. The series is sponsored by the Division of Mycology of the International Union of Microbiological Societies (IUMS) and prepared under the auspices of the International Commission on the Taxonomy of Fungi (ICTF). The first of this series of reports included an introduction to the series explaining the need for name changes. PMID- 2215634 TI - High-Tc brain scan. PMID- 2215635 TI - French research. Keeping faith in technology. PMID- 2215636 TI - HIV infection. Haemophiliacs win right to sue. PMID- 2215637 TI - Animal patents. Australian law finds balance. PMID- 2215638 TI - A woman's place. PMID- 2215639 TI - Porcine problem now. PMID- 2215640 TI - Drug trade. Attacking the mainline. PMID- 2215641 TI - HIV and AIDS. PMID- 2215643 TI - Snow and cholera. PMID- 2215642 TI - Risky arguments about chemicals. PMID- 2215644 TI - Molecular evolution. Old dead rats are valuable. PMID- 2215645 TI - Developmental biology. The promise of gene ablation. PMID- 2215646 TI - Embryology. Activins and induction. PMID- 2215647 TI - Blood in ancient human bone. PMID- 2215648 TI - More light on PCR contamination. PMID- 2215649 TI - High specificity of a phosphate transport protein determined by hydrogen bonds. AB - Transport of the essential nutrient phosphorus--primarily in the form of orthophosphate--into cells and organelles is highly specific. This is exemplified by the uptake of phosphate or its close analogue arsenate by bacterial cells by way of a high affinity active transport system dependent on a phosphate-binding protein; this system is unable to recognize other inorganic oxyanions and is, moreover, distinct from the one for sulphate transport. The phosphate-binding protein is a member of a family of periplasmic proteins acting as initial high affinity receptors for the osmotic shock-sensitive active transport systems or permeases for various sugars, amino acids, oligopeptides, and oxyanions. We report here the highly refined 1.7 A resolution X-ray structure of the liganded form of the phosphate-binding protein. The structure reveals the atomic features responsible for phosphate selectivity, either in monobasic or dibasic form, and the exclusion of sulphate. These features are fundamental to understanding phosphate transport systems and molecular recognition of charged substrates or ions in other biological processes. PMID- 2215650 TI - In vitro genetic analysis of the Tetrahymena self-splicing intron. AB - The availability of methods for the amplification of nucleic acid sequences allows the genetic analysis in vitro of the structural and functional properties of many nucleic acids. We have now developed an in vitro selection and amplification system, and used it to analyse the self-splicing Tetrahymena ribozyme. A much wider range of selective conditions can be used in vitro than is possible with standard in vivo methods, and many more variants can be handled in vitro than in vivo. This method can be used to isolate the wild-type ribozyme, and structural variants that are as active as the wild type, from a pool of over 250,000 variants in only three cycles of selection and amplification. PMID- 2215651 TI - Dutch cure for AIDS is discredited. PMID- 2215652 TI - Soviet accident. Under a cloud. PMID- 2215653 TI - Biomedical research. Sharing a shrinking budget. PMID- 2215654 TI - AIDS research. Study will break new ground. PMID- 2215655 TI - Doubts over 'wonderdrug'. PMID- 2215656 TI - Clinical trials. PMID- 2215657 TI - MRC and peer review. PMID- 2215658 TI - No cancer link. PMID- 2215659 TI - Cell line ownership. PMID- 2215660 TI - Doctor who? PMID- 2215661 TI - Origins of fetal handedness. PMID- 2215662 TI - The scid mutation in mice causes a general defect in DNA repair. AB - Mice homozygous for the scid mutation on chromosome 16 have a severe combined immune deficiency as a result of their inability to correctly rearrange their immunoglobulin and T-cell receptor genes. In scid mice, when precursors for B and T lymphocytes reach the stage of development requiring expression of these surface receptors, a defective recombinase system aberrantly cuts and rejoins the receptor gene segments greatly reducing the efficiency of producing functional receptors. As a result, most scid mice have no detectable B or T lymphocytes. We have demonstrated that the scid defect is not specific to lymphocyte development. Myeloid cells and fibroblasts from scid mice show a marked increase in sensitivity to ionizing radiation, indicating that the scid mutation leads to an inability to repair DNA damage induced by ionizing radiation as well as interfering with rearrangement of the immunoglobulin and T-cell receptor genes. PMID- 2215663 TI - Small rearrangements in structures of Fv and Fab fragments of antibody D1.3 on antigen binding. AB - The potential use of monoclonal antibodies in immunological, chemical and clinical applications has stimulated the protein engineering and expression of Fv fragments, which are heterodimers consisting of the light and heavy chain variable domains (VL and VH) of antibodies. Although Fv fragments exhibit antigen binding specificity and association constants similar to their parent antibodies or Fab moieties, similarity in their interactions with antigen at the level of three-dimensional structure has not been investigated. We have determined the high-resolution crystal structure of the genetically engineered FvD1.3 fragment of the anti-hen egg-white lysozyme (HEL) monoclonal antibody D1.3, and of its complex with HEL. On comparison with the crystallographically refined FabD1.3-HEL complex, we find that FvD1.3 and FabD1.3 make, with minor exceptions, very similar contacts with the antigen. Furthermore, a small but systematic rearrangement of the domains of FvD1.3 occurs on binding HEL, bringing the contacting residues closer to the antigen by a mean value of about 0.7 A for VH (aligning on VL) or of 0.5 A for VL (aligning on VH). This is indicative of an induced fit rather than a 'lock and key' fit to the antigen. PMID- 2215664 TI - RNA polymerase II C-terminal repeat influences response to transcriptional enhancer signals. AB - The large subunit of RNA polymerase II contains a highly conserved and essential heptapeptide repeat (Pro-Thr-Ser-Pro-Ser-Tyr-Ser) at its carboxy terminus. Saccharomyces cerevisiae cells are inviable if their RNA polymerase II large subunit genes encode fewer than 10 complete heptapeptide repeats; if they encode 10 to 12 complete repeats cells are temperature-sensitive and cold-sensitive, but 13 or more complete repeats will allow wild-type growth at all temperatures. Cells containing C-terminal domains (CTDs) of 10 to 12 complete repeats are also inositol auxotrophs. The phenotypes associated with these CTD mutations are not a consequence of an instability of the large subunit; rather, they seem to reflect a functional deficiency of the mutant enzyme. We show here that partial deletion mutations in RNA polymerase II CTD affect the ability of the enzyme to respond to signals from upstream activating sequences in a subset of promoters in yeast. The number of heptapeptide repeats required for maximal response to signals from these sequences differs from one upstream activating sequence to another. One of the upstream elements that is sensitive to truncations of the CTD is the 17-base pair site bound by the GAL4 transactivating factor. PMID- 2215665 TI - Identification of an actin-binding protein from Dictyostelium as elongation factor 1a. AB - Indirect evidence has implicated an interaction between the cytoskeleton and the protein synthetic machinery. Two recent reports have linked the elongation factor 1a (EF-1a) which is involved in protein synthesis, with the microtubular cytoskeleton. In situ hybridization has, however, revealed that the messages for certain cytoskeletal proteins are preferentially associated with actin filaments. ABP-50 is an abundant actin filament bundling protein of native relative molecular mass 50,000 (50K) isolated from Dictyostelium discoideum. Immunofluorescence studies show that ABP-50 is present in filopodia and other cortical regions that contain actin filament bundles. In addition, ABP-50 binds to monomeric actin in the cytosol of unstimulated cells and the association of ABP-50 with the actin cytoskeleton is regulated during chemotaxis. Through complementary DNA sequencing and subsequent functional analysis, we have identified ABP-50 as D. discoideum EF-1a. The ability of EF-1a to bind reversibly to the actin cytoskeleton upon stimulation could provide a mechanism for spatially and temporally regulated protein synthesis in eukaryotic cells. PMID- 2215666 TI - Antibodies from Escherichia coli. AB - Use of Escherichia coli as an expression host has opened up new possibilities in antibody research and its applications. It greatly facilitates rational engineering and random mutagenesis. PMID- 2215667 TI - Genetic engineering. Glasnost for UK release information. PMID- 2215668 TI - Research lobbies. Industry fights back. PMID- 2215669 TI - Research lobbies. New research lobby draws fire. PMID- 2215670 TI - Nobel Prize. Transplantation wins again. PMID- 2215671 TI - Scientific misconduct. Science meets forensic science. PMID- 2215672 TI - UK biotechnology. Biotechnology no longer Wellcome. PMID- 2215673 TI - Radiation exposure. Sellafield under scrutiny. PMID- 2215675 TI - Science sells its soul. PMID- 2215674 TI - Early case of AIDS in the USA. PMID- 2215676 TI - Transcriptional control. Scissors and helical forks. PMID- 2215677 TI - Phospholipid transfer market. PMID- 2215678 TI - Leukaemia risk and plutonium. PMID- 2215679 TI - HIV mutation rate. PMID- 2215680 TI - Monophyletic origin of Lake Victoria cichlid fishes suggested by mitochondrial DNA sequences. AB - Lake Victoria, together with its satellite lakes, harbours roughly 200 endemic forms of cichlid fishes that are classified as 'haplochromines' and yet the lake system is less than a million years old. This 'flock' has attracted attention because of the possibility that it evolved within the lake from one ancestral species and that biologists are thus presented with a case of explosive evolution. Within the past decade, however, morphology has increasingly emphasized the view that the flock may be polyphyletic. We sequenced up to 803 base pairs of mitochondrial DNA from 14 representative Victorian species and 23 additional African species. The flock seems to be monophyletic, and is more akin to that from Lake Malawi than to species from Lake Tanganyika; in addition, it contains less genetic variation than does the human species, and there is virtually no sharing of mitochondrial DNA types among species. These results confirm that the founding event was recent. PMID- 2215681 TI - Transparency and the uniqueness constraint in human and computer stereo vision. AB - The sensation of depth that is obtained with human binocular vision results from the differences in the projection of the world onto the two retinae. The process entails solving the problem of stereo correspondence, which involves choosing the correct matches between left and right image features. Many computational models of stereo vision assume a uniqueness constraint on stereo matching-that is, each feature identified in one image should eventually be matched with only one feature in the other image. This constraint would seem to be justified, as allowing non-unique matches would be tantamount to supposing that the scene entities to which matches relate are in two places at once. The value of the uniqueness constraint for eliminating false matches has been demonstrated in a variety of stereo algorithms. Yet on the basis of psychophysical results Weinshall concluded that it was not used by humans in dealing with certain types of ambiguous random-dot stereograms. We have now tested how Weinshall's stereograms are dealt with by PMF, a stereo algorithm which uses a unique-matches selection procedure in conjunction with a purely local similar-disparity support scheme. We found that PMF produces results that are closely analogous to the psychophysical results. This suggests that Weinshall's experiments should not be interpreted as evidence that the human stereo mechanism establishes non-unique matches. PMID- 2215682 TI - An essential role for a phospholipid transfer protein in yeast Golgi function. AB - Progression of proteins through the secretory pathway of eukaryotic cells involves a continuous rearrangement of macromolecular structures made up of proteins and phospholipids. The protein SEC14p is essential for transport of proteins from the yeast Golgi complex. Independent characterization of the SEC14 gene and the PIT1 gene, which encodes a phosphatidylinositol/phosphatidylcholine transfer protein in yeast, indicated that these two genes are identical. Phospholipid transfer proteins are a class of cytosolic proteins that are ubiquitous among eukaryotic cells and are distinguished by their ability to catalyse the exchange of phospholipids between membranes in vitro. We show here that the SEC14 and PIT1 genes are indeed identical and that the growth phenotype of a sec14-1ts mutant extends to the inability of its transfer protein to effect phospholipid transfer in vitro. These results therefore establish for the first time an in vivo function for a phospholipid transfer protein, namely a role in the compartment-specific stimulation of protein secretion. PMID- 2215684 TI - End now in sight for Gallo investigation? PMID- 2215683 TI - Phylogenetic and genetic evidence for base-triples in the catalytic domain of group I introns. AB - Understanding the mechanisms by which ribozymes catalyse chemical reactions requires a detailed knowledge of their structure. The secondary structure of the group I introns has been confirmed by comparison of over 70 published sequences, by chemical protection studies, and by genetic experiments involving compensatory mutations. Phylogenetic data can also be used to identify tertiary interactions in RNA molecules. This was first done by Levitt, who predicted tertiary interactions in transfer RNA, which were subsequently confirmed by X-ray crystallography. More recently, sequence comparison data have been used to predict tertiary interactions in ribosomal RNA. We have searched a complete alignment of the core regions of group I introns for evolutionary covariations that could not be ascribed to classical Watson-Crick or wobble base pairings. Here we describe two examples of phylogenetic covariation that are most simply explained by postulating hydrogen-bonded base-triples similar to those found in tRNA. Genetic experiments with the Tetrahymena and sunY introns confirm the importance of these interactions for the structure of the ribozyme. PMID- 2215685 TI - Cancer around nuclear plant. PMID- 2215686 TI - Biotechnology. Money no object. PMID- 2215687 TI - AIDS treatment. WHO concern over new drug. PMID- 2215688 TI - Mouse patent a step closer. PMID- 2215689 TI - Medical science. Psychiatric abuses revealed. PMID- 2215690 TI - BSE susceptibility. PMID- 2215691 TI - Human genetics. Deficiencies in sight with the candidate gene approach. PMID- 2215692 TI - Evolution. Between biology and culture. PMID- 2215693 TI - Domestic mercury pollution. PMID- 2215694 TI - Sex-ratio biased organisms. PMID- 2215695 TI - Molecular dynamics simulations in biology. AB - Molecular dynamics--the science of simulating the motions of a system of particles--applied to biological macromolecules gives the fluctuations in the relative positions of the atoms in a protein or in DNA as a function of time. Knowledge of these motions provides insights into biological phenomena such as the role of flexibility in ligand binding and the rapid solvation of the electron transfer state in photosynthesis. Molecular dynamics is also being used to determine protein structures from NMR, to refine protein X-ray crystal structures faster from poorer starting models, and to calculate the free energy changes resulting from mutations in proteins. PMID- 2215696 TI - Intrinsic segmental identity of segmental founder cells of the leech embryo. AB - Segmentation occurs in several animal phyla, and the cellular mechanisms generating this structural periodicity vary considerably. In the leech, an annelid worm, segmental founder cells arise through a fixed cell lineage (Fig. 1), and come together in a longitudinally repeating array through a stereotyped pattern of morphogenesis. In this paper we demonstrate that founder cells forced to differentiate in a foreign segmental environment give rise to their normal, segment-specific clones of neuronal descendants, even in segments in which those neuronal phenotypes would not normally be observed. These findings indicate that the individual founder cells possess segmental identity at or shortly after the time of their birth, and further suggest that such identities are established by a mechanism in which the parent stem cell 'counts' mitotic cycles. PMID- 2215697 TI - Cloning of a gene that is rearranged in patients with choroideraemia. AB - Choroideraemia (tapetochoroidal dystrophy, TCD), a common form of X-linked blindness, is characterized by progressive dystrophy of the choroid, retinal pigment epithelium and retina. Previous studies have assigned the TCD gene to a small segment of the Xq21 band. By making use of reverse genetics strategies we have isolated eight overlapping complementary DNA clones from the same chromosomal region. The corresponding gene is expressed in retina, choroid and retinal pigment epithelium. The cDNAs encompass an open reading frame of 948 base pairs that is structurally altered in eight TCD patients with deletions, and in a female patient with a balanced translocation involving Xq21. These findings provide strong evidence that we have cloned the gene underlying choroideraemia. Elucidation of its function should provide new insights into the molecular mechanisms responsible for this disorder and other hereditary retinopathies. PMID- 2215698 TI - X-ray structure of phospholipase A2 complexed with a substrate-derived inhibitor. AB - Phospholipases A2 play a part in a number of physiologically important cellular processes such as inflammation, blood platelet aggregation and acute hypersensitivity. These processes are all initiated by the release of arachidonic acid from cell membranes which is catalysed by intracellular phospholipases A2 and followed by conversion of arachidonic acid to prostaglandins, leukotrienes or thromboxanes. An imbalance in the production of these compounds can lead to chronic inflammatory diseases such as rheumatoid arthritis and asthma. Inhibitors of phospholipase A2 might therefore act to reduce the effects of inflammation, so structural information about the binding of phospholipase A2 to its substrates could be helpful in the design of therapeutic drugs. The three-dimensional structure is not known for any intracellular phospholipase A2, but these enzymes share significant sequence homology with secreted phospholipases, for which some of the structures have been determined. Here we report the structure of a complex between an extracellular phospholipase A2 and a competitively inhibiting substrate analogue, which reveals considerable detail about the interaction and suggests a mechanism for catalysis by this enzyme. PMID- 2215699 TI - Mandelate racemase and muconate lactonizing enzyme are mechanistically distinct and structurally homologous. AB - Mandelate racemase (MR) and muconate lactonizing enzyme (MLE) catalyse separate and mechanistically distinct reactions necessary for the catabolism of aromatic acids by Pseudomonas putida. The X-ray crystal structure of MR, solved at 2.5 A resolution, reveals that the secondary, tertiary and quaternary structures of MR and MLE are remarkably similar; also, MR and MLE are about 26% identical in primary structure. However, MR has no detectable MLE activity and vice versa. Thus, MR and MLE constitute the first example of enzymes that catalyse different reactions, as opposed to mechanistically identical reactions on different substrates, yet possess sufficient structural and sequence identity that they are likely to have evolved from a common ancestor. The discovery that MR and MLE catalyse different reactions but share a common structural framework has broad implications for the natural evolution of enzymes and metabolic pathways, as well as for the rational modification of enzyme activities. PMID- 2215700 TI - [Transcultural surgical obstetrics]. PMID- 2215701 TI - [Carpal tunnel syndrome]. PMID- 2215702 TI - [Vitamin K prophylaxis necessary in young infants]. PMID- 2215703 TI - [Antithrombotic agents in coronary bypass surgery in The Netherlands]. PMID- 2215704 TI - [Analysis of the urinary sediment]. PMID- 2215706 TI - [Administration of vitamin K to neonates and infants]. AB - The Committee on Infant Nutrition of the Dutch National Cross Association and the Education Bureau on Food and Nutrition, and the Dutch Paediatric Association recommend the administration of a single oral dose of 1 mg vitamin K1 at birth to all healthy infants in order to prevent haemorrhagic disease of the newborn (HDN). Parenteral administration of vitamin K1 at birth is recommended for newborn especially at risk. For infants who are wholly or largely breastfed a daily dose of 25 micrograms vitamin K1 orally is recommended for the first three months, to be increased to 50 micrograms per day in case of additional risk factors. Literature on causes of vitamin K deficiency, incidence of HDN and trends in prophylaxis is summarized and issues which require further clarification are indicated. PMID- 2215705 TI - [Carpal tunnel syndrome]. AB - The results of operative treatment of 117 patients with carpal tunnel syndrome (CTS) are reported. CTS occurred four to five times more frequently in women than in men. It occurred predominantly in the age group 40 to 60 years. Information on the results of operative treatment and residual complaints were obtained by written inquiry (response: 117/126 = 93%). All patients who were dissatisfied or still had complaints were seen in the outpatient department. The duration of follow-up averaged 15 months: 75% of all patients reported good results. In 89% of the patients the preoperative complaints had disappeared. Dissatisfaction with the operative result was often caused by factors not related to the carpal tunnel syndrome. Factors favouring good results were typical complaints, defined as nocturnal paraesthesias on the volar aspect of the hand and abnormal nerve conduction studies. The results obtained with operation under local anaesthesia in the outpatient department are equivalent to those reported of patients operated in the clinical setting. One-third of the patients felt able to return to work or to resume full normal daily activities within 6 weeks, and 2/3 of the patients within 3 months of the operation. PMID- 2215708 TI - [The pneumoportogram, a rare finding in septicemia due to an intra-abdominal abscess]. AB - A man aged 73 is described with radiologically revealed air in the portal vein, a peumoportogram, on the basis of intra-abdominal sepsis. Characteristic of this finding are the air shadows extending far into the periphery of the liver in contrast to an air cholangiogram. It is an ominous sign, mostly secondary to severe intra-abdominal pathology such as ischaemic bowel necrosis, peritonitis or abscesses. Treatment should be aimed at these causes. Prognosis depends on the underlying pathology. PMID- 2215707 TI - [Reliability of blood pressure measurements; comparison of an electronic meter and a mercury manometer in family practice]. AB - The Riva-Rocci indirect method of measuring the blood pressure carries a number of sources of error. A report is presented of a study of the serviceability of an electronic blood pressure meter as compared with the conventional mercury manometer. Seventy-six paired measurements were carried out in patients selected at random using an electronic blood pressure meter and a mercury manometer meeting all Health Council requirements. The systematic error and the incidental error in both measuring procedures were compared. The differences found were so slight as to be negligible in practice. It is concluded that the electronic blood pressure meter in practice constitutes an acceptable substitute for the conventional mercury manometer. PMID- 2215709 TI - [Anti-neuritis vitamin and beriberi. Nobel prize paper. 1929]. PMID- 2215710 TI - [100 years ago discovery of vitamins by Eijkman]. PMID- 2215711 TI - [Biliary ascariasis as complication after cholecystectomy for cholelithiasis]. PMID- 2215712 TI - [The treatment of dog and cat bites]. PMID- 2215713 TI - [Premenstrual syndrome]. PMID- 2215714 TI - [Too much haste is not good either with vitamin K]. PMID- 2215715 TI - [Hippocrates and our hypocrisy]. PMID- 2215716 TI - [Current viewpoints concerning the surgical treatment of aortic coarctation in infants and children]. PMID- 2215717 TI - [The adjuvant treatment of colonic and rectal carcinoma: a step forward]. PMID- 2215718 TI - [Shock wave lithotripsy of gallbladder stones: the initial 54 patients treated in Rotterdam-Dijkzigt]. AB - From April 1988 till May 1990 54 patients with symptomatic gallbladder stones were treated in the University Hospital Rotterdam-Dijkzigt with extracorporeal shock wave lithotripsy (ESWL) followed by oral administration of bile acids (urso and chenodeoxycholic acid). These patients on average underwent 2 sessions of ESWL with an electromagnetic lithotriptor (Lithostar and Lithostar Plus, Siemens AG, Erlangen, FRG). Ultimate disintegration of stones was achieved in 50/54 (93%) patients. The best results were achieved in patients with a solitary gallstone (56% of these patients were stone-free 12 months after ESWL). Four per cent of the patients with 2-10 stones were free of stones 12 months after ESWL). Thirty seven per cent of the patients suffered from biliary colics after ESWL and three patients developed pancreatitis. The administration of oral bile acids were complicated by transient diarrhoea in 20% of the patients. ESWL followed by oral bile acid therapy is a relatively effective and safe therapy for a highly selected population of patients with gallbladder stones. PMID- 2215719 TI - [Hyperostosis cranialis interna; a new syndrome with autosomal dominant inheritance]. AB - A family is described which currently comprises nine individuals, spanning three generations, who are affected with a bone disorder which is confined to the skull and is accompanied by impaired function of the cranial nerves. Radiological examination showed intracranial hyperostosis and osteosclerosis of the calvaria and the base of the skull, without involvement of the mandible or other skeletal bones. Invariably, the main presenting symptom was recurrent facial nerve paralysis from late childhood onwards, but concurrent and variable involvement of the olfactory, optic, vestibular and acoustic nerves was seen; this could be attributed to nerve compression by the bony encroachment into the cranial foramina. Morphological investigations revealed increased formation of bone tissue with a normal structure. The pedigree suggests an autosomal dominant mode of heredity. A review of the literature did not disclose any previous reports on this disorder. PMID- 2215720 TI - [The treatment of ankle edema in the elderly in family practice; when and how often are diuretics used?]. AB - It has long been recommended that one should be careful in prescribing drugs for the elderly. However, it has been shown that more than 20% of those over 65 use diuretics. With advancing age this percentage increases. The sign of ankle oedema appears to be an important factor in the decision to prescribe diuretics. If the oedema is not caused by heart failure, chronic renal failure or hypoproteinaemia, the use of diuretics in ankle oedema is controversial. We used a questionnaire survey to obtain information on the opinions of Dutch general practitioners about the differential diagnosis and treatment of ankle oedema in the elderly. In the questionnaire we presented the case of a 68-year-old woman who complained of ankle oedema without any symptom or sign of heart failure. The questionnaire was sent to 200 Dutch general practitioners (response rate 64%). Chronic venous insufficiency was mentioned by 86% and heart failure by 12% of the responders as the most probable cause of the oedema. The treatment proposed by 59% was advice and (or) compression therapy without drugs, while 40% would have prescribed diuretics. PMID- 2215721 TI - [Risks of diazepam in newborn infants]. AB - In children there is a good effect of diazepam on convulsions after intravenous or rectal administration. This is not the case in neonates. We describe a newborn to whom diazepam was given because of a convulsion and who exhibited serious side effects: coma, hypotonia and feeding difficulties. We point out the risks of using diazepam in neonates. PMID- 2215722 TI - [Indications for an increased possibility of neural tube defects in pregnancies following ovulation induction and/or in-vitro fertilization]. PMID- 2215723 TI - [When the heart beats in the throat]. PMID- 2215724 TI - [Children and trauma: decreasing mortality, different care]. PMID- 2215725 TI - [Immunology and virology of HIV infection: current concepts in the pathogenesis of AIDS]. PMID- 2215726 TI - [(Chemo)prevention and second primary tumor of the head and neck region]. PMID- 2215727 TI - [Cervical epidural spinal cord stimulation in infantile encephalopathy]. AB - The effect of Cervical Epidural Spinal cord Electrical Stimulation (E.S.E.S.) was studied in 15 patients with cerebral palsy. Spasticity and dyskinesia, daily functioning and the emotional and physical burden of this therapy for the patients were examined. Twelve patients did not continue the treatment after completing the study, because of lack of symptomatic or functional improvement and many complications due to broken or migrated electrodes. Two patients still continue E.S.E.S. and a third is awaiting replacement of a broken electrode. None of these three patients showed a clear improvement of the ADL scale or the disability score. E.S.E.S. cannot be recommended as a symptomatic treatment for cerebral palsy patients. PMID- 2215728 TI - [Percutaneous transluminal coronary angioplasty in patients older than 70 years; short- and long-term results]. AB - PTCA was performed in 166 patients older than 70. The primary angiographic and clinical success rates were 85% and 86%, respectively. A total of 15 major complications occurred in 10 patients (6%): 4 patients died (2%), 6 patients underwent urgent bypass surgery (4%), the incidence of acute myocardial infarction was 3% (5 patients). The 4-year survival rate was 84 +/- 8%. During the follow-up period 8 patients (5%) sustained a nonfatal myocardial infarction, 21 patients (13%) underwent a second and (or) third balloon dilatation and 17 patients (10%) underwent bypass surgery. At the end of the observation period 68% of the survivors had a sustained improvement of the functional class. This was associated with a significant reduction of the antianginal therapy. These data demonstrate that PTCA can be performed safely and effectively in patients over 70. PMID- 2215729 TI - [Analysis of antibodies against human immunodeficiency virus on a voluntary basis in healthy persons in Amsterdam 1988 and 1989]. AB - At the Municipal Health Service of Amsterdam it is possible to be tested for HIV antibodies after signing an informed consent. In 1988, 1247 persons were tested (797 men, 450 women) and in 1989, 1400 persons (869 men, 531 women). Fifty-eight persons were identified as HIV-seropositive for the first time (1988: 24 men, 3 women; 1989: 28 men, 3 women). All but one woman belonged to a risk group or had had sexual contact with a person from a known risk group. In 1989 no increase in the percentage of HIV-seropositive persons was seen. In our (selected) group of persons in 1988 and 1989 we saw no transmission of HIV outside the known risk groups. PMID- 2215730 TI - [Children and accidents: decreasing mortality, different care]. AB - In order to explore the demand for trauma care facilities for children with severe injuries in the University Hospital of Rotterdam, the departments of Paediatric Surgery and Epidemiology initiated a study of mortality, morbidity and patterns of trauma care. The standardized mortality rate in the region declined by 40% between 1979 and 1986, as did the clinical prevalence of trauma injuries, expressed by the number of days spent in hospital per 100,000 children. This was in agreement with the national epidemiological data. The number of hospital admissions for childhood injuries in the University Hospital of Rotterdam stabilized in recent years, which may be considered a relative increase. Moreover the number of children with severe injuries admitted to Intensive Care Units increased by 46%, which was mainly due to Intensive Care admissions of children living outside Rotterdam. Obviously, another pattern of referral of these patients has developed in the south-west of The Netherlands. The decrease of the number of severe injuries in childhood together with the complexity of trauma care and the increasing number of physicians raises questions on the maintenance of skills. This is an argument for centralization of trauma care for severely injured children, which to some extent has already been implemented in this region. PMID- 2215731 TI - [Gynecomastia in testicular tumors]. AB - The incidence of gynaecomastia among 224 patients treated between 1981 and 1989 for testicular cancer was studied retrospectively. Gynaecomastia was present as an initial symptom in 25 (11%) patients and developed after chemotherapy or radiotherapy in 19 (9%) patients. Gynaecomastia was mainly seen in patients with high tumour stages. It therefore points to an unfavourable prognosis. PMID- 2215733 TI - [Eurothemes. Physicians and patients without borders]. PMID- 2215732 TI - [Cardiomyoplasty: a new alternative in chronic heart failure]. AB - The technique of cardiomyoplasty to support the failing heart as applied in the first two patients in The Netherlands is reported. Indications are presented for the selection of patients who might benefit from a cardiomyoplasty procedure, considering its experimental nature. PMID- 2215734 TI - [Aspirin and pregnancy]. PMID- 2215735 TI - [Bavaroise and an epidemic of Salmonella enteritidis]. PMID- 2215736 TI - [Emergency care for severely injured patients]. PMID- 2215737 TI - [Consensus about consensus]. PMID- 2215738 TI - [Serum creatinine level as a measure of kidney function]. PMID- 2215739 TI - ['Globus'; real or virtual?]. PMID- 2215740 TI - [Brain tumors do not metastasize?]. PMID- 2215742 TI - [Symptoms and injuries of the locomotor system in dancers]. PMID- 2215741 TI - [Current viewpoints on the risks of various types of fat distribution]. PMID- 2215743 TI - [Prolonged pregnancy and management: what is on time?]. PMID- 2215744 TI - [Critical illness polyneuropathy]. AB - Critical illness polyneuropathy is a syndrome of neuromuscular complications after artificial respiration. The authors present the data of their own 22 patients all suffering from severe flaccid tetraparesis, areflexia and muscle atrophy, after an average of two weeks on artificial respiration. The prognosis is relatively favourable. The multi-conditional causes are discussed with emphasis on the combination of polyneuropathy and myopathy. The role of plasma factors such as cachectin, which is identical to tumour necrosis factor (TNF), is described. Attention is drawn to this important illness which occurs especially in patients in the intensive care unit with problems in the weaning from artificial respiration. PMID- 2215745 TI - [Generalized histoplasmosis in 3 patients with an HIV infection]. AB - Three patients with generalized histoplasmosis and the acquired immunodeficiency syndrome (AIDS) are described. Symptoms of generalized histoplasmosis in patients with AIDS are not specific and concomitant opportunistic infections frequently occur. Two patients suffered from an infection by Mycobacterium tuberculosis, one patient had Pneumocystis carinii pneumonia, and one had cerebral toxoplasmosis. One patient had serological results positive for Histoplasma capsulatum. Two of the three patients showed rapid clinical improvement on amphotericin B but this was temporary and all patients died within 5 months. PMID- 2215746 TI - [Long-term results of the Swanson prosthesis for the treatment of lunate osteomalacia]. AB - From 1972 to 1982 a silicone implant arthroplasty was performed in 18 patients with Kienbock's disease grade III. In May 1988 all patients had a clinical and radiological re-examination. In the course of time reoperations were performed in 4 patients because of (sub)luxation of the prosthesis. Because of this operation most of the patients had less pain and retained an acceptable function of the wrist. Influence on working circumstances had been considerable in 8 patients. One patient received a disability pension because of this disease. Radiological examination often revealed increased degenerative changes in carpo-radial and intercarpal joints as well as proximal migration of the capitate. There was no clear relationship between residual complaints and function at the follow-up examination and the radiological findings. PMID- 2215747 TI - [Medical decisions around life's end, the study by instruction of the Commission Remmelink]. PMID- 2215748 TI - [Proposal of legislation Medical Management Contract and patients' rights]. PMID- 2215749 TI - [Orthostatic hypotension in the elderly]. PMID- 2215750 TI - [Deep venous thrombosis in pregnancy: diagnosis, treatment and prevention]. PMID- 2215751 TI - [The Douglas abscess]. PMID- 2215752 TI - [Status and future of autopsies]. PMID- 2215753 TI - [Arterial insufficiency of the legs: pathophysiological basis of the physical diagnostic examination]. PMID- 2215754 TI - [AIDS, intervention studies and pressure from patients]. PMID- 2215755 TI - [Measurement of undesirable urine loss in women]. PMID- 2215756 TI - [Galactorrhea]. PMID- 2215757 TI - [Dissection of cervical arteries as a cause of cerebral ischemia or cranial nerve dysfunction]. AB - Nine patients with dissections of the cervical arteries are presented. Dissections cause approximately three per cent of non-haemorrhagic stroke and are usually observed in young and middle-aged patients. Dissections very often give rise to head or neck pain. Carotid artery dissection may lead to lower cranial nerve dysfunction and an incomplete Horner's syndrome in case of subadventitial dissection, and to cerebral ischaemia in case of subintimal spread. Vertebral artery dissection may cause brain stem ischaemia (subintimal dissection) or in rare cases a subarachnoid haemorrhage (subadventitial spread). The history frequently reveals a (trivial) traumatic event. Diagnosis is usually established by angiography or MRI. The prognosis is good and recurrences are rare. Treatment with anticoagulants or acetylsalicylic acid seems recommendable, though scientifically unproven. PMID- 2215758 TI - [Aspiration cytology of palpable breast lesions: testing of the results using the PALGA data (Pathological Anatomical National Automated Archives)]. AB - For the testing of the results of 1233 breast punctures performed on 1132 women in the period 1985-1988, the question was studied whether a less time-consuming procedure than status examination might be used. The national computerized record office where all data on cytological and histological diagnostics per patient are centralized (PALGA) offered the possibility of determining whether and, if so, with what results histological examination of the breast had been carried out. Histological follow-up examination proved to be available of 476 punctates. In case of abnormal cytological findings without subsequent histological examination, the final diagnosis was made on the basis of the clinical findings (53 punctates; 4.6% of the women examined). In case of non-abnormal cytological findings without subsequent cytological or histological follow-up examination, the lesion was regarded as benign. It proved technically feasible with use of these final diagnoses to arrive at a numerical evaluation of aspiration cytology for the laboratory. These characteristics are valuable in making the decision whether, given a particular result of puncture biopsy, women with a palpable breast tumour should or should not be operated, provided the characteristics are always used only in combination with clinical and mammographic diagnostics. The method is also appropriate for evaluation of other forms of cytodiagnostic examination. PMID- 2215759 TI - [The use of a mixture of citrated erythrocytes and heparin plasma for exchange transfusions]. AB - In 1985 a mixture of red cells collected in citrate anticoagulant with plasma derived from heparinized blood was introduced in Amsterdam to perform exchange transfusions in newborns. This heparin mixture has physiological levels of electrolytes, calcium and glucose, can be delivered on short notice and carries a minimal risk of transmission of infectious diseases because all blood components are tested for hepatitis B antigen and antibodies against syphilis and the human immunodeficiency virus. Retrospectively we evaluated 54 children treated in 1986 and 1987 with exchange transfusions using this heparin mixture. An adequate decrease in bilirubin values when necessary was observed while neither changes in sodium, potassium, calcium or glucose values nor adverse effects on the pH value were recorded. However, a remarkable transient thrombocytopenia was found following exchange transfusion with a decrease of the platelet count to an average of 39% of the initial value. PMID- 2215760 TI - [From the history of the Emma Pediatric Hospital]. PMID- 2215761 TI - [Drugs after 1992; a comparison with yet many unknowns]. PMID- 2215762 TI - [Herpes zoster and acyclovir in normal and dysfunctional general immunity, also that due to AIDS]. PMID- 2215763 TI - [Clinical importance of selective decontamination in patients in the intensive care unit]. PMID- 2215764 TI - [Arterial circulatory disorders; not just smoking or cholesterol]. PMID- 2215765 TI - ['You should be that one exception'; risk perception and choice behavior in medical technology]. PMID- 2215766 TI - [Pharmaco-morbidity linking: a potential instrument for post-marketing surveillance]. PMID- 2215767 TI - [The value of animal models for clinical studies of antimicrobial agents]. PMID- 2215768 TI - [Transposition of the posterior tibial tendon in neuropathic talipes equinovarus]. AB - Equinovarus foot deformity as seen in neurologic disease is often caused by imbalance in muscle tone. One of the possible operative procedures to correct this deformity is transposition of the posterior tibial tendon. The effect of this intervention is disputed in the orthopaedic literature. The results of this procedure are presented in a retrospective study of 9 children (11 feet). The mean follow-up period was 19 months (8-40). In all cases but one the results were satisfactory. The indications and complications of this operation are discussed. PMID- 2215769 TI - [With decreasing mortality does the incidence of acute myocardial infarct decrease also?]. AB - It is unknown how many cases of acute myocardial infarction, fatal or non-fatal, are treated non-clinically. Using various approaches to the available figures from hospital records and statistics of causes of death, it appears possible, however, to conclude that apart from the number of deaths the number of cases, also, has decreased fairly markedly in the last few years. PMID- 2215771 TI - [Pharmaco-morbidity linking: a pilot study of its technical possibilities in The Netherlands]. AB - The feasibility has been studied of linking pharmacy-based dispensing data and hospital-based morbidity data by using as a linkage key a combination of gender and birth date of the patient and of his general practitioner (GP) code. Firstly, the records of one pharmacy (14,686 patients) and those of one hospital (8475 admissions in 1987) were linked on the basis of date of birth and gender. This resulted in 3,715 matching record pairs. To a random sample of 1,713 of these pairs the GP code was added. Subsequently these pairs were validated by reference to the original medical and pharmaceutical records with a procedure that guaranteed that only the name and address of the patients could be compared without having access to the clinical or pharmaceutical record of an individual. We were able to link records with a sensitivity of 91.4% (95%-confidence interval: 88.8-94.0) and a specificity of 96.0% (95%-confidence interval: 94.5 97.5). In conclusion, probabilistic linkage of pharmaceutical and medical data with the combination of gender, date of birth and GP code facilitates successful record linkage. PMID- 2215770 TI - [Waist-to-hip ratio in Dutch women and its relationship with self-reported diabetes mellitus, hypertension and cholecystectomy]. AB - The waist-to-hip circumference ratio is recognized as a measure of body fat distribution and as a risk indicator of premature mortality. The distribution of waist-to-hip ratio values in 12,000 Dutch women aged between 40 and 75 years is presented. In addition, the statistical associations between the waist-to-hip ratio and the degree of overweight as well as the prevalence of self-reported diabetes mellitus, hypertension, and cholecystectomy are described. The odds ratios for the prevalence of these disorders increased progressively with increasing waist-to-hip ratio. The age-adjusted odds ratios for women with a waist-to-hip ratio greater than 0.85 in comparison to those with a waist-to-hip ratio less than 0.70 were 4.8, 4.6 and 5.8 for diabetes mellitus, hypertension, and cholecystectomy respectively. The presented data on waist-to-hip ratio can, in combination with Quetelet's index, serve as a guide in the interpretation of measured waist-to-hip ratios in women between 40 and 75 years of age. PMID- 2215773 TI - [Oxybuprocaine drops and eyedrops should not be given to patientson prescription]. PMID- 2215772 TI - [Histoplasma capsulatum infection, a manifestation of AIDS unusual for The Netherlands]. AB - The history of 29-year-old male from Surinam with antibodies to HIV-1 and long lasting fever, lymphadenopathy, pain in the right upper abdomen and a granulomatous hepatitis is described. The patient suffered from disseminated histoplasmosis, a fungal disease rare in The Netherlands, which is the indicator disease for the diagnosis of AIDS (CDC-IVCI). It is stressed that in seropositive patients coming from endemic areas, including Surinam, the possibility of this disease should be considered. PMID- 2215775 TI - [Reported patients with infectious diseases in 1989]. PMID- 2215774 TI - [Inefficacy of oral contraceptives during administration of minocycline]. PMID- 2215776 TI - Toward a kinder, gentler practice. PMID- 2215777 TI - Spinal cord compression--an oncologic emergency. AB - Spinal cord compression secondary to epidural metastatic tumor is an emergency clinical situation that requires prompt diagnosis and treatment if permanent neurologic damage is to be prevented. Physicians caring for patients with cancer must maintain a high index of suspicion for this problem. Back pain is a common clinical situation in the general population but in the cancer patient, one should consider this sign indicative of possible spinal cord compression even though a long tumor-free interval has occurred since the original diagnosis of neoplasm. The diagnosis is established by thorough neurologic examination, plain x-rays, myelography, CT and MRI scanning. Once the diagnosis is established, treatment is instituted with steroids, decompressive surgery and postoperative irradiation or external irradiation alone depending upon the emergent nature of the clinical situation. Regardless of the initial treatment, patients with spinal cord compression require management in a multi-disciplinary fashion. Early therapy will result in the best relief of symptoms and maintenance of the ability to walk. The ultimate prognosis of such patients is very dismal in view of the metastatic nature of their disease but prompt diagnosis and treatment is necessary to prevent devastating sequelae for the patients and their families. PMID- 2215778 TI - Cytogenetic confirmation of clinical diagnoses in Nebraska. PMID- 2215779 TI - Periparturitional shigellosis. AB - A case is reported in which Shigella sonnei induced both maternal disease (chorioamnionitis) and neonatal disease (pneumonia) in the immediate periparturitional period. The role of Shigella sonnei as a periparturitional pathogen is discussed. PMID- 2215780 TI - Right aortic arch with aberrant left subclavian artery demonstrated by MR imaging: case report. PMID- 2215781 TI - Physician reimbursement update. PMID- 2215782 TI - Can residents of nursing homes be freed from restraints? PMID- 2215783 TI - Registered nurse license renewal. PMID- 2215784 TI - NNA-PAC update. PMID- 2215786 TI - Advanced education for nursing administration: MSN, MBA, or MPA? PMID- 2215785 TI - Nurses training educates Doctor. Interview by JoAnne Young. PMID- 2215787 TI - Physicians' and nurses' attitudes toward AIDS. PMID- 2215788 TI - [Position of removable partial dentures within prosthetic dentistry]. AB - Recent developments in restorative dentistry resulted in a shift towards elderly patients with regard to the application of removable partial dentures (RPD). The half life time of a metal frame RPD is ten years. Negative effects of a RPD on the remaining dentition can be prevented by adequate oral hygiene, which is supervised in a recall program with an individually adjusted interval. Periodontal factors seem to be more important in the design of a RPD than biomechanical factors. Simplicity is a prime guideline in the design, especially in free-end situations. PMID- 2215790 TI - [Rapid maxillary suture expansion]. AB - Rapid maxillary expansion is a technique with an old but controversial history. Bio-mechanics and apparatus have largely involved over the years and the procedure is generally accepted. Discussion concerns only the patient age range on which the therapy is applicable. Fourteen to eighteen seems the accepted age limit. Three essential parameters determine the success of the expansion: degree of interlocking, synostosis and skeletal resistance from the surrounding osseous tissues. PMID- 2215789 TI - [Mandibular atrophy and metabolic bone loss]. AB - Radiological studies in edentulous patients with and without atrophy of the mandible and radiological, histomorphometrical and endocrinological studies in edentulous patients with a severe atrophy of the mandible and treated by ridge augmentation has shown that: metabolic bone loss, histologically and endocrinologically characterized as a secondary hyperfunction of the parathyroid glands, is a causal factor in the pathogenesis of mandibular atrophy. PMID- 2215791 TI - [Fragmentation of sialoliths]. AB - An in vitro experiment proved that a sialolith can be disintegrated, but that also serious damage is caused to the teeth and dental restorations. Therefore, no experiment was carried out on a patient, although it proved to be possible to position a patient on a lithothriptor in a way that the shock wave of the apparatus would hit the sialolith without passing the brain, eyeballs and laryngeal skeleton. PMID- 2215792 TI - [Dentist in an information society]. AB - Many commentators say that at present we are living in an information society, a society in which the main sources of national income are communication and information. This article aims at the question how the dentist's practice will be influenced by the information society. The dentist's role in the information society is described as an information broker between the dental science and the public, the patients. In that role the dentist is confronted with two developments, i.e. 'information overload' and 'rising expectations as to the possibilities of medical help'. The article concludes with a plea for 'good health education'. Against the background of the developments at the side of the public 'good health education' is not to be understood as 'more health information' for the public, but as 'more quality in health information'. PMID- 2215794 TI - [Periodontal care in The Netherlands]. AB - The dental care in The Netherlands is unable to cope with the threat resulting from periodontal diseases. Changes resulting from alterations within the dental care system will, however, enable larger groups within the population to receive periodontal therapy in the near future. PMID- 2215793 TI - [Dentist and scientific dental information in mass media]. AB - Mass media, such as newspapers and magazines and to a lesser degree TV and radio can provide the public with a lot of scientific information about dental diseases. Especially when it concerns research results with news value or controversial issues. Dentists regarded by the public as the most reliable sources of scientific information about dentistry, can get into problems by the publication of such issues in mass media. Particularly when patients ask questions about developments in certain fields of dentistry (for example periodontology or implantology) covered by the mass media. In this article the importance and the value of communication of scientific information are discussed. The relevance for dentistry is illustrated by means of a series of articles on scientific dental subjects published, during fifteen years, in a Dutch national newspaper. Finally the responsibility of dental faculties and professional organisations when they provide research results to the press and other mass media is pointed out. PMID- 2215795 TI - [Periodontal diseases in The Netherlands]. AB - The extend and severity of periodontal diseases in The Netherlands are discussed using data of a large epidemiologic oral health survey in 1986. The perspective on treatment is presented with some notes on the basic issues in health and disease. The often heard statement, that the periodontal disease problem is much more severe in developing countries compared with the industrialized countries, could not be confirmed. PMID- 2215796 TI - [Non-plaque related periodontal diseases]. AB - Non-plaque related periodontal diseases are rather rare, and may be based on a wide range of lesions, both benign and malignant. The clinical and radiographic signs often mimic those of the common plaque-related diseases and, therefore, may significantly postpone proper diagnosis and treatment. PMID- 2215797 TI - [Diagnosis of plaque related periodontal diseases]. AB - Plaque related periodontal diseases include the area of slight gingivitis and advanced destructive periodontitis featuring loss of periodontal attachment and alveolar bone destruction. The progression of periodontitis may vary from rapid progressive disease, to stable condition but also remission of the disease. Not all patients are equally susceptible to destructive periodontal disease. Therefore, the 'risk concept' was introduced. The diagnosis of periodontal diseases is based on the assessment of periodontal inflammation and loss of attachment. The diagnostic parameters are described as well as their prognostic value. PMID- 2215798 TI - [Treatment planning for patients with periodontal disease]. AB - The planning and execution of dental treatment in patients suffering from (severe) periodontal disease has to be carried out thoroughly and systematically. Based on a proper diagnosis and prognosis (problem analysis), a temporary treatment plan (problem solution) will be formulated. The initial (periodontal) treatment is concluded with a reevaluation. After this new diagnosis, and if necessary adjustment of the original goal of the treatment plan, a definite treatment plan can be effected. Also in this plan, the therapy must be carried out in separate phases with evaluations in between. Primarily, the periodontal therapy must be finalized, after which the definite restorative-prosthetic treatment can be carried out. A good cooperation between the dentist, dental hygienist and patient is of prime importance to achieve a permanent result. The principles of periodontal treatment planning are discussed in this contribution. PMID- 2215799 TI - [Microbiological aspects in the treatment planning of periodontal disease]. AB - A large number of bacterial species are found in the periodontal pocket. It has been shown that the composition of the subgingival microbiota can differ significantly between individual pockets in one patient, as well as between different subjects. These different types of microfloras can be characterized by indicator bacteria. These indicator bacteria are strongly associated with active periodontal breakdown. Therefore, these microorganisms can be useful in the periodontal treatment of individual patients. It also supports the use of antibiotics in specific forms of periodontal disease. The application of microbiological data in diagnosis and treatment planning in four severe periodontitis patients is illustrated. PMID- 2215801 TI - [Dentist periodontist]. AB - In this article criteria and procedures are discussed that are being used to qualify dentist-periodontists (Tandarts-Parodontologen). Also a description is given of the tasks of such a periodontist: consultation, treatment and education. Furthermore figures are presented with respect to experiences of the first group of dentists that have recently been qualified as dentist-periodontist. PMID- 2215800 TI - [Guided tissue regeneration in periodontology: an overview]. AB - Conventional periodontal treatment consisting of scaling and rootplaning with or without flap surgery, with or without bone grafting, does not lead to regeneration of the periodontium. Experiments based on the principle of guided tissue regeneration have shown that the formation of 'new attachment' is no longer impossible. PMID- 2215802 TI - [Patient education in periodontal health]. AB - To achieve a successful periodontal treatment result, a good and lasting co operation between therapist and patient is essential. For this reason, the patient must be adequately informed about the development, symptoms and treatment of periodontitis and about the necessity of a high level of self performed oral hygiene. Individual information and instruction by the dentist and dental hygienist is most suited in these cases. PMID- 2215804 TI - [Sharpening of periodontal instruments]. AB - Sharp hand instruments are the first pre-requisite for scaling and root planing. Different sharpening techniques are reported, and the time at which an instrument is evaluated for its sharpness or dullness is indicated. The shape and form of several instruments are described together with the appropriate sharpening technique. PMID- 2215803 TI - [Four years experience with a periodontal health education program for 12-15-year old Dutch schoolchildren]. AB - A dental health education program on periodontal disease for 12-15-years-old schoolchildren during a period of four years (1986-1989) was organised. A course package was developed for secondary schools, whereby an evaluation of the course material was carried out both quantitatively and qualitatively. The amount of material requested by the schools exceeded the expectations. The content of the material appeared to be adequate for both the pupils as well as teachers. The education strategy was successful in reaching the target group. The school appears to be an excellent place for this type of dental education program. For the future it may be advisable to focus more on a target group with a low education level. PMID- 2215805 TI - [Treatment planning in partial prosthodontics]. AB - The aim of the initial treatment is to eliminate active complicating factors from the partial edentulous mouth, such as caries, periodontal disease and occlusal discrepancies. After evaluation of the results of the initial treatment the prosthetic treatment can be started. A specific preparation of the mouth is necessary to accommodate the remaining dentition to the design of the removable partial denture. PMID- 2215806 TI - [Expert systems in orthodontics]. AB - A review and concept is given of possible applications of expert and other information systems in orthodontics. The key to success probably lies in the fact that all relevant problems can be expressed in a formal system. Informatization projects can be an exciting and useful aspect in the field of orthodontics, if one proceeds with a modular approach. PMID- 2215807 TI - [Beagle dogs in periodontal research: a review]. AB - This review intends to focus on the role dogs play in periodontal research. Dogs have given insight in the occurrence, the etiology, the pathogenesis and the treatment of periodontal diseases although some differences with humans exist. The occurrence of root resorption, the better healing capacity and the progression rate of periodontitis are among those differences. Knowledge of the periodontal conditions in dogs is required to be able to evaluate the obtained results and its implications for humans carefully. This seems especially true for the ongoing research in tissue regeneration. PMID- 2215808 TI - [Dental aspects of snoring and the obstructive sleep apnea syndrome]. AB - An overview is presented of causes, consequences and treatment possibilities of snoring and the obstructive sleep apnea syndrome. Snoring and the obstructive sleep apnea syndrome are widespread sleep disorders, which may result in serious physical and psychosocial problems. The contribution of oral surgery and orthodontics to the team management of these patients is discussed. PMID- 2215809 TI - [Dental self care of the dentate Dutch population: oral hygiene]. AB - This paper is part of a series on national oral health survey in The Netherlands (LEOT-project). It presents the results as for the oral hygiene behavior and its determinants of the dentate Dutch population. Nearly all dentate Dutch people (97.5%) reports to clean their teeth with an average of nearly two times a day. The use of other cleaning means is not very common. There is a fair amount of knowledge about dental hygiene. The great majority (about 85%) indicates that toothbrushing for them is an automated behavior, a habit. PMID- 2215810 TI - [Classification of edentulous mandibles in preventive implantology]. AB - The aim of preventive implantology is to prevent or delay the resorption of edentulous alveolar ridges. The classifications of the resorption stages of the mandible which are now in use, are not applicable to preventive implantology. After anatomic research it was concluded that the resorption of the alveolar ridge of the mandible should be classified in three stages. Loaded as well as unloaded implants can function as tooth root analogues in maintaining the volume of the edentulous ridge. PMID- 2215811 TI - [Revised recommendations about the use of fluoride]. AB - At the end of 1989 the organisation for dental health education in The Netherlands 'Ivoren Kruis' presented new recommendations about the use of fluorides. The advice was based on a report of an expert committee and was put in a definite form in consultation with representatives of a number of dental and medical professional organisations. For children below the age of five a toothpaste with 250 ppm F- is recommended. Fluoride tablets (with 0.25 mg F-) are recommended for children below the age of 12. The advised number of fluoride tablets is reduced compared with the former recommendations. PMID- 2215812 TI - [Clinical procedures in removable partial prosthodontics]. AB - Restoring oral function with removable partial dentures includes treatments running along several steps and procedures. These treatments should be carefully planned. The dentist should know the steps to be taken to achieve the desired end result. PMID- 2215813 TI - [The (post)graduate training of orthodontists]. PMID- 2215814 TI - [Solitary bone cyst of the jaws: report of 22 cases]. AB - A retrospective study of 22 solitary bone cysts was made. Almost all lesions were detected as an incidental finding on the radiographs. The dentist should be aware of this asymptomatic radiolucency which is most commonly seen in the mandible, in order to avoid redundant dental treatment. PMID- 2215815 TI - [Gardner's syndrome: report of a case]. AB - Gardner's syndrome consists of multiple polyposis of the large intestine and soft and hard tissue tumors. The syndrome should be considered in case of supernumerary teeth, odontomas, osteoma and soft tissue tumors. These findings often precede colonic involvement. Careful attention should be directed towards the family history. The importance of this syndrome lies in the great tendency of the polyps to become malignant. Dentist and oral surgeon play an important role in the early detection of this syndrome and thus prevention of malignant degeneration of the intestinal polyps. PMID- 2215816 TI - [Dental fluorosis in relation to the use of fluoride tablets]. AB - The prevalence of dental fluorosis on the buccal tooth surfaces was investigated in 15-year-old children in the towns Tiel and Culemborg, using the Tylstrup Fejerskov scoring system. A study done in 1980 revealed that at the age of six, 53% of the children in Tiel and 30% of the children in Culemborg took one or more fluoride tablets (0.25 mg F-) daily. In Tiel the tablets were provided free of charge in a centre for child dental care. On the basis of the number of tablets supplied in the age period 1.5-6 years, most of the 15 year olds in Tiel could be classified as regular, irregular or non-tablet user. Only mild fluorosis (TF score 1, 2 or 3) was found. The percentage of children with one or more buccal surfaces affected with fluorosis was 24 in Tiel and 22 in Culemborg. The percentages of buccal surfaces with fluorosis were 6 (Tiel) and 7 (Culemborg). In Tiel the percentages of surfaces with fluorosis in the groups regular, irregular and non-tablet users were 12%, 5% and 2% respectively. PMID- 2215817 TI - [Simultaneous removal of lower wisdom teeth with local anaesthesia: a pilot study]. AB - To determine whether it is justified to remove both mandibular third molars in one session, 69 patients were treated single-sided and 53 patients double-sided using local anaesthesia (Ultracain D-S forte). All patients were healthy. The mean age was 24.0 years. No significant differences in complaints were found. Therefore, it seems justified to remove mandibular third molars double-sided in one session in healthy young patients. PMID- 2215818 TI - [Tooth replacement in the anterior region: specific problems and standard options]. AB - The problems involved in the loss of anterior teeth differ essentially from those in the premolar/molar region. Firstly, missing anterior teeth result in unacceptable changes in appearance and speech, making treatment mandatory. Secondly, the dentist has to consider specific aspects, such as aesthetics, resorption of the alveolar bone, loading of the abutment teeth, form of the clinical crown and incisal guidance. Treatment options comprise orthodontic closure, periodontally supported removable and fixed appliances and appliances supported by implants. The advantages and disadvantages of the different options are indicated. PMID- 2215819 TI - [Replacement of anterior teeth by implants]. AB - The replacement of anterior teeth by implants and crowns is the most recent one of the available treatment possibilities. The most important advantage of this method is the prevention of resorption of the alveolar bone and undisturbed integrity of the remaining other teeth. PMID- 2215820 TI - [Esthetics and removable partial dentures: a contradiction?]. AB - Although modern developments in dentistry constrict the indication of removable partial dentures, there is still a number of situations in which a partial denture may contribute to the re-establishment of function, esthetics included. Thereto it is a necessity that all parts of the construction are carefully designed, with special attention for color and form. Choice of the artificial teeth (material), the handling of the acrylic and an adequate anchoring are all important factors in reaching an optimal result. PMID- 2215821 TI - [Replacement of anterior teeth with bridges]. AB - Missing incisors and canines may be replaced with preferably gold-porcelain bridges. To be acceptable in an esthetical sense, the bridge demands, apart from a correct colour and shape, a healthy periodontium, the latter being the subject of this paper. The way in which the outline is prepared, the relationship between depth of the preparation and marginal gingiva and the prevention of periodontal trauma are discussed. PMID- 2215822 TI - [Replacement of anterior teeth and maintenance care]. AB - A study undertaken in a general dental practice shows post-operatively a beneficial effect of regular subgingival scaling. A relative short time investment, once to thrice a year, appears to stabilize the periodontal situation of abutment teeth, even periodontally weak ones. PMID- 2215823 TI - [Glass ionomer cement used as a retrograde filling material after apicoectomy: a review]. AB - When an apicoectomy is performed, using retrograde sealing with amalgam, the healing of the periapical area is not always perfect. In a number of cases the cause of this imperfect healing may be due to the improper sealing ability and the moderate tissue compatibility of amalgam. A literature study has been carried out, based on the assumption that glass ionomer cement will provide a better sealing and will cause less tissue reaction. It appeared that, at least in theory, glass ionomer cement is to be preferred to amalgam when it comes to apical sealing properties and tissue reaction. In terms of usability, resorption, hardness and costs no significant differences were found. The conclusion is drawn that glass ionomer cement is an equal or perhaps even better alternative for retrograde amalgam. PMID- 2215824 TI - [Plax more effective than water?]. AB - Ten persons participated in a cross-over study in which the effect of rinsing with Plax and subsequent toothbrushing was compared with water rinsing and subsequent toothbrushing. Plaque was evaluated at baseline and after rinsing and toothbrushing. Bacterial and epithelial cells were counted in the material that was removed by rinsing and brushing. In addition the dry-weight of this material was determined. The differences between Plax and water in plaque reduction, the number of bacterial and epithelial cells in the material removed from the mouth were statistically not significant. The weight of the material removed by the rinsing and brushing was higher after rinsing with Plax. This was caused by the more vigorous removal of epithelial cells by Plax than by water. PMID- 2215825 TI - Serotonin receptor antagonists: a novel class of anti-emetics. PMID- 2215827 TI - Is there a relationship between thyroid function and serum osteocalcin in women with multinodular goitre? A preliminary report. AB - The relationship between thyroid function and serum osteocalcin was studied in a population of 27 women with multinodular goitre and normal serum concentrations of thyroid hormones. Seven patients were found to have suppressed TSH levels (less than 0.1 mU/l) as measured by an immunoradiometric assay. Osteocalcin was statistically significantly correlated with serum free thyroxine (FT4), both in the total population and in the subpopulation of patients with TSH greater than or equal to 0.1 mU/l (r = 0.61; P less than 0.001, resp. r = 0.51; P less than 0.05). Mean (+/- SEM) serum osteocalcin and FT4 were higher in the patients with suppressed TSH than in those with TSH greater than or equal to 0.1 mU/l (10.6 +/- 1.9 vs. 7.1 +/- 0.6 micrograms/l; P less than 0.05, resp. 16.3 +/- 1.4 vs. 13.3 +/- 0.5 pmol/l; P less than 0.02). This study suggests that women with multinodular goitre who proceed to autonomous function are at risk of developing osteoporosis even when thyroid hormone concentrations are in the normal range. PMID- 2215826 TI - Effect of calcitonin on gastric emptying and on postprandial gastrin and insulin release in patients with type I gastric ulcer. AB - In a double-blind placebo-controlled study, the effect of calcitonin on gastric emptying and on serum concentrations of gastrin, insulin, glucose, calcium and phosphorus after a mixed solid-liquid meal was examined in six patients with type I gastric ulcer. Synthetic salmon calcitonin 415 pmol i.v. was given as a bolus followed by a 90-min infusion to reach an overall dose of 62.25 pmol.kg-1. Gastric emptying of a radiolabelled meal was measured with a gamma camera. Calcitonin suppressed gastric emptying in all patients examined. The mean gastric transit time, MTT90, increased from 38.1 +/- 0.4 min after placebo to 43.1 +/- 0.6 min after calcitonin (P less than 0.001). Calcitonin significantly blunted the postprandial gastrin release: AUC0-90 10,398 +/- 2886 ng. l-1 min (placebo) and 8238 +/- 2573 ng. l-1 min (calcitonin), P less than 0.05, and abolished the postprandial insulin release--AUC0-90 2244 +/- 230 mU.l-1 min (placebo) vs. 638 +/- 198 mU.l-1 min (calcitonin), P less than 0.01. A steady increase in the serum glucose during calcitonin infusion, reaching up to 5.6 +/- 0.31 mmol.l-1 at the end of the infusion, was observed. Calcitonin did not significantly affect serum calcium or phosphorus concentrations. The authors conclude that a delayed gastric emptying is to be expected in patients undergoing calcitonin treatment. PMID- 2215828 TI - Ursodeoxycholic acid treatment in a patient with primary biliary cirrhosis. AB - A women with stage I-II primary biliary cirrhosis was treated with ursodeoxycholic acid (UDCA). During UDCA treatment a notable improvement in biochemical liver profile was achieved. Liver histology did not deteriorate after one year UDCA. UDCA offers a promising non-toxic alternative in the treatment of PBC. PMID- 2215829 TI - An unusual case of cystic lymphangiomatosis of the spleen. AB - Isolated lymphangiomatosis of the spleen is rare. When present, it is usually considered to be accompanied by splenomegaly. We describe a case of cystic lymphangiomatosis in a patient with a normal-sized spleen. While ultrasound, angiography and computed tomography are considered to complement each other in reaching a preoperative diagnosis of splenic lymphangiomatosis, in the present case, magnetic resonance imaging proved to be an additional helpful non-invasive diagnostic method. PMID- 2215830 TI - Valsalva termination of ventricular tachycardia in myocardial infarction. AB - A 66-yr-old patient with recurrent monomorphic ventricular tachycardias subsequent to a previous myocardial infarction is reported. The tachycardia could repeatedly be terminated by the Valsalva manoeuvre. Procainamide, infused shortly before, possibly had an additional effect. As far as we know, this is the first report of ventricular tachycardias, as a result of an old myocardial infarction, that could be terminated by the Valsalva manoeuvre. PMID- 2215831 TI - Fatal acute liver failure associated with pirprofen. Report of a case and a review of the literature. AB - This report is about a 71-yr-old woman who suffered from acute liver failure, induced by the nonsteroidal antiinflammatory drug, pirprofen. She presented with jaundice 6 weeks after starting treatment with 800 mg pirprofen daily. She is the fifth patient described in the literature to die from pirprofen-induced hepatotoxicity. PMID- 2215832 TI - Chromosome 14: a breakpoint in non-Hodgkin's lymphomas. AB - In non-Hodgkin's lymphoma, chromosome abnormalities are found that are characteristic for the type of the lymphoma. These chromosomal abnormalities provide a tumour-specific marker and seem to play a role in the oncogenesis of the lymphoma. Chromosome 14 is involved in many lymphomas. The immunoglobulin heavy chain gene and the alpha and delta chain genes for the T cell receptor are located on this chromosome, genes which are essential for the function of B or T lymphocytes. These genes are involved in the specific translocations seen in non Hodgkin's lymphoma. Their role and the role of oncogenes in the oncogenesis of non-Hodgkin's lymphoma are discussed. The oncogene tcl-1 is also located on chromosome 14. PMID- 2215833 TI - Results in patients with Graves' disease. PMID- 2215834 TI - Sweet's syndrome. PMID- 2215835 TI - Pancreatitis: an unusual manifestation of late syphilis? PMID- 2215836 TI - The relationship between densitometry of the radius and vertebral fractures. AB - In 105 postmenopausal women with clinical suspicion of osteoporosis single photon absorptiometry (SPA) of the forearm and fracture percentage of the thoracic and lumbar spine were estimated. SPA was performed on the commonly used mid-radius site as well as on a modified distal radius site where radius and ulna are separated by five mm. Spine fracture percentage was inversely correlated with mid radius SPA (r = -0.49) but more closely with distal radius SPA (r = -0.61). With bone mineral density values above 0.400 g/cm2 on the distal radius, no fractures were found. Between 0.325 and 0.400 g/cm2, 35% of the patients showed vertebral fractures but only up to a maximum of 30%. Below 0.325 g/cm2, 89% of the women had crushed vertebrae, often more than 30% of those measured. In conclusion, these results indicate that modified distal radius densitometry is superior to the commonly used mid-radius measurement and has some predictive value for the presence of vertebral fractures. PMID- 2215837 TI - Thrombocytopenic purpura as first manifestation of human immunodeficiency virus type I (HIV-1) infection. AB - We report three cases of thrombocytopenic purpura associated with HIV-1 infection. The clinical picture is indistinguishable from classic autoimmune thrombocytopenic purpura (AITP). All three patients initially responded to treatment with high dose methylprednisolone. One patient had an incomplete remission on low dose prednisone, while another responded to zidovudine treatment. The third patient underwent splenectomy because he showed no response to treatment with low dose prednisone or zidovudine. The pathogenesis of HIV associated thrombocytopenic purpura (HIV-TP) is still controversial. Two hypotheses are frequently mentioned: non-specific deposition of circulating immune complexes and complement versus specific auto-antibodies against platelets are suggested to be the cause of the increased clearance of platelets. In cases of severe thrombocytopenia, the therapy of first choice is initial high dose methylprednisolone, followed by either low dose prednisone in the presence of a relatively unaffected cellular immunity, or zidovudine, when the cellular immunity is already severely impaired. PMID- 2215838 TI - Thrombocytopenia associated with mycoplasma pneumoniae infection. AB - The case of a patient with immune thrombocytopenia associated with mycoplasma pneumoniae infection is described. The thrombocytopenia was considered to be provoked by the infection and disappeared gradually after antibiotic treatment. PMID- 2215840 TI - Methodological problems of clinical trials in dementia. PMID- 2215839 TI - Postprandial blood pressure reduction. AB - Recently it has been shown that, after a meal, blood pressure may fall in the elderly, in patients with autonomic failure and in patients on haemodialysis. This review deals with the available data on postprandial blood pressure reduction, the clinical significance and some pathophysiological hypotheses. The mechanism is not fully understood, but postprandial blood pressure reduction seems to be related to glucose related factors, since blood pressure only falls after oral glucose loading, but not after oral fructose, fat or protein loading. Vasoactive gastrointestinal peptides may play a role in the glucose induced vasodilation of splanchnic vasculature, but attempts to identify such peptides have been unsuccessful. The role of insulin in postprandial blood pressure reduction remains to be elucidated, but it does not appear to have any influence on systemic vasodilation or baroreflex response. Although the clinical significance of postprandial blood pressure reduction remains uncertain, patients can be advised in several ways on how to avoid this symptom. Treatment of hypertension, small carbohydrate meals, caffeine and treatment with the somatostatin analogue SMS 201-995 may have a beneficial effect. Patients on haemodialysis with symptomatic hypotension should not consume meals during the procedure. PMID- 2215841 TI - Dimensional versus nosographic approach to Alzheimer's disease: therapeutic implications. AB - Negative results in therapeutic trials in Alzheimer's disease (AD) usually account for the nonefficacy of the presently tested drugs. However, methodological flaws in the design of these studies, related to the commonly used nosographic approach, can also be implicated in the lack of demonstration of beneficial results. With regard to the heterogeneity of clinical manifestations of AD, the interest of the dimensional, transnosographic approach to cognitive deficits and behavioral disturbances in dementia is suggested for these trials. Both approaches can also be combined, according to the presumed biochemical action of the tested drug in the preclinical studies and the aim of the trial. PMID- 2215842 TI - Assessment of functional changes in Alzheimer's disease. AB - Functional difficulties occur in all patients with Alzheimer's disease. Instrumental skills (shopping, handling money) are involved first, then self-care activities (toileting, dressing). Drug trials in intermediate stage Alzheimer's disease should monitor self-care activities with structured diaries and rating scales. PMID- 2215843 TI - Neuropsychological assessment of cognitive change in dementia. AB - The problem of long-term assessment of cognitive change in dementia is defined as that of avoiding floor and ceiling effects in testing. Unlike diagnosis, the establishment of norms is viewed as secondary. This perspective allows the formulation of strategic guidlines in devising test batteries for longitudinal studies of cognitive change in dementia. A number of tests complying with these guidelines are described, tapping a wide range of cognitive abilities such as semantic analysis of verbal and visual material, semantic memory, object recognition, visuoconstruction and serial planning. PMID- 2215844 TI - Comparison of seven psychometric instruments used for evaluation of treatment effect in Alzheimer's dementia. AB - Standards of assessment of treatment effect in Alzheimer's disease have been wanting. We report here a comparison of seven methods of assessment of the severity of Alzheimer's disease used in demented subjects (n = 18) and in nondemented controls (n = 18). The instruments tested were the Names Learning test, the Orientation test, the Mini-Mental State Examination, the Alzheimer's Staging Scale (the AZSS), the Global Deterioration Scale, the Clinical Dementia Rating Scale, and the Alzheimer's Deficit Scale (ADS). Two examiners did the testing per telephone methodology, and test/retest design. Results showed all tests to be reliable. A ceiling and/or basement effect was noted in all but the AZSS and the ADS. PMID- 2215845 TI - Objective assessment in dementia: automated psychometric tests and the P3. AB - Event-related potentials have been shown to be closely correlated with cognitive functioning and it has been suggested that one such potential, the P3, can act as an objective and sensitive measure of the degree of dementia. The P3 is no longer thought of as a diagnostic tool in dementia; however, longitudinal changes in the P3 latency can be used to follow the course of a dementing illness or to assess effects of therapy. It is possible that the measurement of P3 latency may prove useful in the selection of patients with early dementia. Automated psychometric tests are also of considerable value in assessing large numbers of cognitively impaired subjects. The advantages of using these tests and their usefulness in multicentre drug trials is discussed. PMID- 2215847 TI - Methodological problems of clinical trials in multi-infarct dementia. AB - In about 30% of the cases suffering from MID an unequivocal diagnosis can be made only on the basis of histopathological evidence. The imperfect diagnosis has a relevant impact on the methodology to be followed in therapeutic trial. The following points have to be considered in a therapeutic trial: (1) distribution of the patients expected to come to the observation, (2) the expected effectiveness of the treatment, (3) the likelihood of obtaining statistical significant results and (4) the required size of the study. The diagnostic inaccuracy gives rise to a decrease in the chance of yielding a statistically significant result and on the other hand produces an increase in the required number of subjects to be submitted to the trial. PMID- 2215846 TI - Assessment of outcome in clinical trials in Alzheimer's disease. AB - Assessment instruments used to measure psychological outcome in clinical trials in dementia include rating scales of activities of daily living and scales of cognitive function. Each has specific advantages and limitations. The popularity of certain dementia scales results from their demonstrated correlation with measures of pathological change, implying that they accurately reflect dementia severity. It is argued that the inference of test validity on the basis of such clinicopathological correlation may be unfounded. Alzheimer's disease is a heterogeneous disorder, encompassing varying profiles of cognitive disability. Dementia scales, which are weighted in favour of specific areas of dysfunction, may be differentially sensitive to the deficits of certain patients relative to others, thus yielding a spurious measure of dementia severity. PMID- 2215848 TI - Long-term experience of a trial in multi-infarct dementia. AB - A report is given on the natural history of multi-infarct dementia (MID) in 94 patients over a period of 5 years and describes neuroimaging criteria that may be used in order to more reliably separate vascular (VD) from primary degenerative types of dementia (DTD). The annual mortality rate of MID patients was 13%. Age and nocturnal confusion were found to be the most efficient predictors for fatal prognosis. Psychosocial adjustment, in contrast, indicated better outcome. In respect to differential diagnosis MRI revealed infarcts, basal ganglia lacunes and confluent white matter lesions as the most effective discriminators between VD and DTD. The typical patchy pattern found in almost half of the patients with VD, and significant differences in 5-7 Hz range as shown by EEG mapping can also be used for increasing the accuracy of the clinical diagnosis. PMID- 2215850 TI - Studies on new, centrally active and reversible acetylcholinesterase inhibitors. AB - We have synthesized the tertiary amines of pyridostigmine and neostigmine, 3 pyridinol dimethylcarbamate (norpyridostigmine) and 3-dimethylaminophenol dimethylcarbamate (norneostigmine) respectively, and we have tested their abilities to cross the blood-brain barrier and inhibit mouse brain AChE activity. The in vivo inhibition of AChE activity by norpyridostigmine reaches 72% at 10 minutes which is comparable to that seen with physostigmine (73% at 10 minutes). Inhibition by norneostigmine is less effective (50% at 10 minutes) and approaches that obtained with tetrahydroaminoacridine (57% at 10 minutes). These data show that both norpyridostigmine and norneostigmine cross the blood-brain barrier and that they are effective inhibitors of mouse brain AChE activity. These drugs could be useful in the treatment of memory impairment associated with Alzheimer's disease, and other memory disorders. PMID- 2215849 TI - The serotonin 5-HT1D receptor: a progress review. AB - Most of the known neurotransmitters interact with more than one type of receptor. Some of them even dispose of receptor subtypes to exert their actions. Serotonin, far from being an exception to that, possesses at least 3 classes of receptors, which have all been reported to be heterogeneous, although convincing data only exist for the 5-HT1 class. This name has been proposed in 1979, two years before the introduction of 'A' and 'B' in the nomenclature to account for the observed heterogeneity of these sites. The 5-HT1C receptor subtype was first described in 1984 and the last member of the family, named 5-HT1D, was characterized in 1987. The pharmacological profiles, the signal transducing systems and the anatomical localizations, both at the regional and cellular levels, of all these subtypes have been investigated and possible functions have been proposed for each of them. Moreover, last and most definitive demonstration of the subtype individuality, the gene or complementary DNA coding for the 5-HT1A and 5-HT1C (and 5-HT2) receptors have been cloned and sequenced. Such data are still missing for 5-HT1D (and 5-HT1B) receptors, but will certainly be provided in the next few years. However and waiting for this decisive clue, the characterization of the 5 HT1D subtype leaves no doubt concerning its significance as a function 5-HT receptor. This review will concentrate on the characteristics of this subtype of 5-HT receptor. PMID- 2215851 TI - Effect of phosphatidylserine on the basal and GABA-activated Cl- permeation across single nerve membranes from rabbit Deiters' neurons. AB - The permeation of labeled Cl- ions across single plasma membranes from Deiters' neurons has been studied in the presence of various concentrations of phosphatidylserine (PS) on their extracellular side. PS reduces significantly basal Cl- permeation only at 10(-5) M on the membrane exterior. No effect was found at other concentrations. GABA activable 36Cl- permeation is heavily reduced and almost abolished at 10(-11) - 10(-5) M phosphatidylserine. This exogenous phosphatidylserine effect is difficult to interpret in relation to the function of the endogenous phospholipid. However, it may be involved in the epileptogenic effect in vivo of exogenous phosphatidylserine administration to rats. PMID- 2215852 TI - Acetyl-L-carnitine as a precursor of acetylcholine. AB - Synthesis of [3H]acetylcholine from [3H]acetyl-L-carnitine was demonstrated in vitro by coupling the enzyme systems choline acetyltransferase and carnitine acetyltransferase. Likewise, both [3H] and [14C] labeled acetylcholine were produced when [3H]acetyl-L-carnitine and D-[U-14C] glucose were incubated with synaptosomal membrane preparations from rat brain. Transfer of the acetyl moiety from acetyl-L-carnitine to acetylcholine was dependent on concentration of acetyl L-carnitine and required the presence of coenzyme A, which is normally produced as an inhibitory product of choline acetyltransferase. These results provide further evidence for a role of mitochondrial carnitine acetyltransferase in facilitating transfer of acetyl groups across mitochondrial membranes, thus regulating the availability in the cytoplasm of acetyl-CoA, a substrate of choline acetyltransferase. They are also consistent with a possible utility of acetyl-L-carnitine in the treatment of age-related cholinergic deficits. PMID- 2215853 TI - Effects of acute and subacute cocaine administration on the CNS dopaminergic system in Wistar-Kyoto and spontaneously hypertensive rats: I. Levels of dopamine and metabolites. AB - Effects of acute and subacute cocaine administration on dopamine (DA) and its metabolites in striata and nucleus accumbens of nine week-old Wistar-Kyoto and spontaneously hypertensive rats were studied. Levels of DA,3,4 dihydroxphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined by HPLC-EC. There were no differences in DA levels in striata and nucleus accumbens between control WKY and SHR. Levels of DA in two brain regions were unaffected in groups treated acutely with cocaine. Both strains showed a significant increase in striatal HVA 2 hr after cocaine injection. Seven day treatment declined DA levels in striatum of WKY and in nucleus accumbens of SHR. However, only WKY treated subacutely with cocaine showed significantly increased HVA either with or without changes in DOPAC in nucleus accumbens and striatum, respectively. Increased DOPAC/DA and HVA/DA ratios appeared only in striatum of WKY and in nucleus accumbens of SHR following subacute treatment. These results suggest that subacute cocaine administration affects DA levels in striata and nucleus accumbens differently between WKY and SHR. PMID- 2215854 TI - Effects of acute and subacute cocaine administration on the CNS dopaminergic system in Wistar-Kyoto and spontaneously hypertensive rats: III. Dopamine uptake. AB - The characteristics of dopamine uptake after acute and subacute cocaine administration were determined in striata from WKY and SHR. In acutely-treated (40 mg/kg, s.c.) rats, significant increases in the Vmax of dopamine uptake were observed 30 min after the cocaine injection in both strains, without changes in Km values. The in vitro IC50 for cocaine was significantly decreased at 30 min in WKY and at 2 h in SHR. However, the in vitro IC50 for GBR-12909 was significantly increased at 30 min and at 2 h in both strains following cocaine administration. In both strains, the density (Bmax) of the [3H]GBR-12935 binding site was significantly increased at 30 min and at 2 h with no changes in Kd. In subacutely treated (20 mg/kg, twice daily for 3 or 7 days) rats, a significant increase in the Km for dopamine uptake was observed in 7 day treated SHR. The in vitro IC50 for GBR-12909 was significantly increased in 3 day treated WKY. The results suggest that cocaine administration alters dopamine uptake and characteristics of dopamine uptake sites in the rat brain. PMID- 2215855 TI - Transport of valproate and its effects on GABA uptake in astroglial primary culture. AB - The antiepileptic drug Na(+)-valproate (VPA) is a broadspectrum anticonvulsant. It has been proposed to be involved in the inhibitory mechanisms of GABA-ergic systems. In this study, transport of the drug and possible influence on the GABA uptake were investigated in primary astroglial cell cultures from newborn rat cerebral cortex. The results show a Na+ and K+ independent high affinity uptake for VPA, with km and Vmax not significantly different from those observed for the GABA uptake. In the presence of the drug, the Km-value of the GABA uptake increased. The GABA uptake inhibitors guvacine, (RS)-Cis-4-OH-nipecotic acid and 4,5,6,7-tetrahydroisoxazolo (4,5- c) pyridin-3-ol (THPO) did not influence upon the uptake of VPA, suggesting a transport mechanism for the drug, separated from the GABA uptake carrier. PMID- 2215857 TI - Binding of flunitrazepam to differentiating neurons cultured in a chemically defined, hormone-supplemented medium. AB - [3H]Flunitrazepam (FNZ) binding to cortical neurons from fetal rat brain was investigated in vitro. The use of a synthetic medium specific for neurons made it possible to plot a developmental curve of 3H-FNZ binding in an almost pure neuronal culture. Detectable specific binding was present in vitro at time 0 (that is, the 16th gestational day). A progressive increase of binding, due to an increment in the number of recognition sites, was observed on the subsequent days. The affinity of the specific binding sites to 3H-FNZ was enhanced by the addition of exogenous GABA, whereas the density was not affected. PMID- 2215858 TI - Supra-additive activation of guinea-pig superior cervical ganglion adenylate cyclase by PGE2 and D-Ala2-Met-enkephalinamide: role of GTP. AB - The effects of guanine nucleotides were tested on basal and agonist-modulated adenylate cyclase in guinea-pig superior cervical ganglion crude membrane preparations. GTP gamma S and Gpp(NH)p dose-dependently stimulate, while GDP beta S inhibits, both the basal and the prostaglandin E2-stimulated enzyme activity. Low GTP doses, up to 10(-5) M, stimulate, while higher doses inhibit, the ganglionic adenylate cyclase. The GTP-induced diphasic pattern is maintained also in the presence of prostaglandin E2, D-Ala2-Met-enkephalinamide, or a combination of the two drugs. However, the opioid inhibits the enzyme activity, but only at high GTP doses, while the prostaglandin stimulates the enzyme at all GTP concentrations. The effect is potentiated by a combination of prostaglandin and enkephalin. The enhancing effect of the prostaglandin and of the combination with enkephalin is maximally expressed at high, almost physiological, GTP doses. PMID- 2215856 TI - Red cell phenylalanine is not available for transport through the blood-brain barrier. AB - The possibility that red cell-sequestered amino acids such as phenylalanine are available for transport through the brain capillary wall, i.e., the blood-brain barrier (BBB), in vivo was investigated in the present studies with the carotid artery injection technique. Control studies included the examination of the availability of red cell-sequestered solutes such as phenylalanine or D-glucose to liver cells in vivo using a portal vein injection technique. The results show that red cell-sequestered phenylalanine is not available for transport through the BBB or into rat liver in vivo, but human red cell-sequestered D-glucose is available for uptake by liver following portal injection. Therefore, given favorable kinetics it is possible for red cell-sequestered solute to be available for uptake by tissues. However, in the case of neutral amino acids such as phenylalanine, red cell-sequestered amino acid is not available for transport through the BBB in vivo. PMID- 2215859 TI - Thiobarbituric acid-reactive material content and enzymatic protection against peroxidative damage during the course of cryogenic rabbit brain edema. AB - The relationship between free radicals reactions and the cell detoxifying system was investigated during the development of brain edema following a cryogenic lesion in the rabbit cerebral cortex. The amount of TBA-reactive material present six hours after freezing was less than in the controls, then increased at 48 and 96 hours. The activity of superoxide dismutase (SOD) decreased 6 hours post injury; at the same time, we observed a stimulation of catalase activity. The glutathione peroxidase activity (GSH-Px) rose 96 hours post-lesion. The decrease of TBA-reactive products could result from an elimination rate that exceeds generation. PMID- 2215860 TI - Effect of short- and long-term exposure to low environmental temperature on brain regional GABA metabolism. AB - Single exposure of adult male rats to low environmental temperature (LET, 12 +/- 0.5 degrees C) for 2 h significantly increased the hypothalamic and striatal GABA levels without affecting those in other regions of brain. The activity of glutamate decarboxylase (GAD) was elevated in hypothalamus (H) and corpus striatum (CS) under these conditions. GABA accumulation rate (measured with ethanolamine-O-sulfate, an inhibitor of GABA-transaminase) was also increased in both H and CS of rats exposed to LET for 2 h. Unlike after a single exposure, the repeated exposure (2 h/day) for 7, 15, and 30 consecutive days did not change the hypothalamic GABA metabolism. No change in GABA metabolism was observed in CS when rats were repeatedly exposed to LET for 7 consecutive days. Prolongation of repeated exposure to LET (2 h/day) for 15 and 30 consecutive days decreased the striatal GABA level and increased the activity of GABA-transaminase, although GAD activity was not altered under these conditions. These results suggest that single exposure to LET accelerates GABA synthesis and may reduce the GABAergic activity in both H and CS; whereas repeated exposure to LET for 15 or 30 consecutive days enhances GABAergic activity with the stimulation of GABA utilization only in CS without affecting its synthesizing process. Thus, it may be suggested that the hypothalamic and striatal GABA system may play a characteristic role in response to short- and long-term exposure to LET. PMID- 2215861 TI - Regional excitatory and inhibitory amino acid levels in epileptic El mouse brain. AB - Inbred mutant El mice are highly susceptible to convulsive seizures upon "tossing" stimulation. The levels of excitatory (e.g. glutamate and aspartate) and inhibitory amino acids [e.g. gamma-amino-butyrate (GABA)] were examined in discrete regions of stimulated El mice [El(+)], non-stimulated El mice [El(-)] and ddY mice, which do not have convulsive disposition. In comparison with ddY, a general increased levels of aspartate, glutamate, glutamine, and taurine were detected in brain regions of El(-). The levels of GABA and glycine were almost the same in ddY and El(-). Compared to El(+), the levels of aspartate, glutamate, glutamine, and GABA in El(-) were either the same or higher. In the case of taurine and glycine, the levels in El(-) were either the same or lower than El(+). Alanine is special in that El(-) have a higher level than El(+) in hippocampus but lower in cerebellum. Furthermore, while marked changes were registered in several brain regions, none of the amino acids investigated showed any significant differences in the hypothalamus of three different groups of mice. PMID- 2215863 TI - [Accessory nerve decompression for the treatment of spasmodic torticollis]. PMID- 2215862 TI - Sodium dependency of GABA uptake into glial cells in bullfrog sympathetic ganglia. AB - The kinetics of sodium dependency of GABA uptake by satellite glial cells was studied in bullfrog sympathetic ganglia. GABA uptake followed simple Michaelis Menten kinetics at all sodium concentrations tested. Increasing external sodium concentration increased both Km and Vmax for GABA uptake, with an increase in the Vmax/Km ratio. The initial rate of uptake as a function of the sodium concentration exhibited sigmoid shape at 100 microM GABA. Hill number was estimated to be 2.0. Removal of external potassium ion or 10 microM ouabain reduced GABA uptake time-dependently. The effect of ouabain was potentiated by 100 microM veratrine. These results suggest that at least two sodium ions are involved with the transport of one GABA molecule and that sodium concentration gradient across the plasma membrane is the main driving force for the transport of GABA. The essential sodium gradient may be maintained by Na+, K(+)-ATPase acting as an ion pump. PMID- 2215865 TI - [Dissecting aneurysm of the vertebral artery as a cause of Wallenberg's syndrome]. AB - Although it is well known that Wallenberg's syndrome is caused by occlusion of the vertebral artery (VA) or the posterior inferior cerebellar artery (PICA), the etiology of the occlusion is rarely documented. During the course of Wallenberg's syndrome, patients often complain of headache. We thought that these headaches might be caused by dissecting aneurysm (DA) of the vertebral artery, and so we studied the incidence of DA in our cases with Wallenberg's syndrome. Although many variants exist, Wallenberg's syndrome encompasses several neurological symptoms due to a disorder of the nucleus and nerve tracts located in the lateral part of the medulla. We diagnosed our patients as having Wallenberg's syndrome on the basis of symptoms such as loss of pain and temperature sensation in the unilateral face and contralateral body, cerebellar ataxia, and dysphasia. We investigated 22 cases of Wallenberg's syndrome over a five-year period, and excluded patients who developed subarachnoid hemorrhage upon onset of the syndrome. Our cases can be divided into two groups; one with severe stenosis or occlusion of VA (n = 15) and the other with occlusion of PICA (n = 5). The angiograms of the two remaining patients showed no abnormal findings. The mean age of the VA group (42.5 yrs.) was younger than that of the PICA group (64.2 yrs.). The age distribution of the PICA group is similar to that of other occlusive cerebrovascular diseases. Seven cases of the VA group demonstrated aneurysmal dilatation and luminal stenosis, and so they were diagnosed as having dissecting aneurysm of VA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2215864 TI - [Management results of primary intracranial malignant lymphoma]. AB - Nineteen cases of primary malignant lymphoma of the central nervous system were reported. The clinical characteristics, diagnostic procedure and therapeutic method, especially concerning chemotherapy, were analysed. The following conclusions were obtained: 1) histological classifications and surgical procedures were not factors involved in prognosis. 2) radiotherapy was regarded as an effective but a palliative treatment. 3) combined chemotherapy for systemic malignant lymphoma, such as VEMP, VEP, COPP, seemed to be of little use for intracranial malignant lymphoma. 4) intra-arterial administration of high-dose methotrexate, ACNU and intravenous administration of high-dose cytosine arabinoside can be expected to be a useful chemotherapeutic approach. PMID- 2215866 TI - [Epilepsy after operation for ruptured intracranial aneurysm]. AB - Fifty-five patients who underwent surgery for ruptured aneurysm of the anterior circulation were evaluated with respect to postoperative epilepsy. Prophylactic treatment with anticonvulsants had been carried out in all patients. The overall incidence of the postoperative epilepsy was 23.6% (13/55). The mean latency between the operation and the first seizure was 11 months (range, 8 days to 5 years). The most important risk factors by statistical analyses were multiple aneurysms, preoperative severity, severe subarachnoid hemorrhage, intracerebral hematoma, normal pressure hydrocephalus, EEG abnormalities in the chronic stage, intracerebral low density area on CT-films and neurological deficit. Other risk factors were aneurysm of MCA and early operation for aneurysm. Our opinions concerning postoperative anticonvulsant therapy for aneurysmal patients are as follows. 1) Prophylactic treatment with anticonvulsant should be administered to all patients who have undergone aneurysm surgery. 2) The risk factors should be considered in determining the duration of medication with the anticonvulsant. 3) The treatment with the anticonvulsant should be performed while monitoring the clinical course, EEG findings, plasma concentration level of the anticonvulsant and side effects of the drugs. PMID- 2215867 TI - [Encapsulated chronic intracerebral hematoma caused by venous angioma of the basal ganglia: a case report]. AB - A case is reported of venous angioma at the right basal ganglia simulating the encapsulated chronic intracerebral hematoma. A 29-year-old man was admitted to our hospital on July 14, 1988 with a two-month history of headache. Neurological examination revealed left homonymous lower quadrantic anopsia. CT scans showed a mosaic high density lesion at the right basal ganglia with extensive adjacent edema. MRI revealed that the high density lesion on CT scans was the combination of a reticulated core of mixed signal intensity with a surrounding rim of decreased signal intensity. The lesion was accompanied with extensive edema. Followed up CT scans showed the transformation of the lesion and ring-shaped enhancement. A right frontotemporal craniotomy was performed on August 9, 1988. After thorough dissection of the sylvian fissure and small corticotomy to the insula, a tough capsule was seen. There was blood in various stages of organization in the capsule. A histological examination gave a diagnosis of venous angioma in the membrane similar to the outer membrane of chronic subdural hematomas. Postoperatively, the patient showed slight left motor weakness, but it gradually improved and he was discharged on foot, on October 19, 1988. There have been a lot of reports about angiographically occult intracranial vascular malformation (AOIVM). But AOIVM at the basal ganglia is rare, and to our knowledge, only 8 cases have been reported. In our case, the presence of adjacent extensive edema, and ring-shaped enhancement on CT scans confused the preoperative diagnosis. Those findings might have been caused by encapsulation. By using CT scans and MRI, a complete and accurate diagnosis was impossible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2215868 TI - [Intracranial hematoma associated with acquired immunodeficiency syndrome (AIDS): case report]. AB - The authors report a case of intracranial hematoma associated with AIDS. A male aged 21 had been treated with infusion of factor VIII to control hemophilia A. He fell down and hit his right occipital region. Immediately after the impact, he became comatose. When he was hospitalized 30 minutes after the injury, a herniation sign was recognized. CT scan revealed right acute subdural hematoma that showed mixed density. This hematoma was successfully removed with HITT (hematoma irrigation with trephination therapy) and he recovered almost completely. However he died when the intracerebral hematoma bled suddenly on the 20th day after surgery. We assumed the hematoma was related to vasculitis induced by AIDS. Three points in this case impressed us. First, HITT is very useful for treating acute subdural hematoma associated with AIDS. Second, the patient's condition may deteriorate suddenly through intracerebral hematoma originating from AIDS-related vasculitis, although the coagulation factors are well maintained. Third, a manual for management of cases of AIDS is necessary to avoid confusion among the medical staff. PMID- 2215869 TI - [Meningioma of pineal region]. AB - A 58-year-old man was admitted to our hospital upon his request for an operation on a hemifacial spasm that had developed twelve years ago. The hemifacial spasm on the left side was the only positive neurological findings at the time of admission. However, a pre-operative neuroradiological examination revealed a meningioma originating in the falco-tentorial junction. Left neurovascular decompression was initially performed and was followed by the excision of the tumor through a right parietooccipital approach. The pathological diagnosis was meningothelial meningioma. The patient was discharged with no neurological deficit. There have been only a few reports on pineal meningioma and even now this type of tumor is considered to be rare. Some similar cases reported in the literature are reviewed. The clinical aspects, clinical features and the pathological entity are discussed. PMID- 2215870 TI - [An adult case of malignant choroid plexus papilloma in the lateral ventricle and the cerebellopontine angle revealed simultaneously]. AB - An adult case of malignant choroid plexus papilloma is very rare. This report is an adult case of malignant choroid plexus papilloma revealed in the lateral ventricle and in the cerebellopontine (CP) angle simultaneously. A 37-year-old man was admitted to the hospital complaining of headache, nausea, and a floating sensation on August 29, 1984. Neurological examination on admission revealed bilateral papilledema, left dysmetria and horizontal nystagmus. CT scan revealed a slightly high density round mass in the right lateral ventricle and a cystic mass with mural nodule in the left CP angle. The intraventricular mass and mural nodule were enhanced moderately and homogeneously. The initial surgery was for removal of the CP angle tumor, and 8 days later removal of the lateral ventricle tumor was carried out. The histology of these tumors was the same and revealed malignant choroid plexus papilloma. Postoperative radiation therapy was carried out 70Gy to the brain (whole brain; 50Gy, focal; 20Gy) and 30Gy to the whole spine. About 2 years later paraparesis, lower cranial nerve palsy, and disturbance of consciousness had progressed gradually. He died of the severe recurrence of the tumor in the brain stem, and multiple dissemination in the spinal cord on September 6, 1987. There was no recurrence of tumor in the right lateral ventricle. This is a very rare case of malignant choroid plexus papilloma which was revealed in both the supra- and infratentorial regions simultaneously. They may have developed independently or they may have arisen through subarachnoid seeding. Radical removal of the tumor is important to prevent recurrence of malignant choroid plexus papilloma. PMID- 2215871 TI - [Intraventricular arachnoid cyst appearing with attacks of orbital pain: case report and review of the literature]. AB - While there have been 5 cases of intraventricular arachnoid cyst published in the literature, the occurrence in the anterior horn of the lateral ventricle has not been reported. We report a case of intraventricular arachnoid cyst of the anterior horn causing attacks of orbital pain. A 30-year-old man was admitted with frequent attacks of orbital pain on his right side. Neurological examination revealed no abnormality. Plain CT showed a cystic dilatation of the anterior horn of the right lateral ventricle, and enhanced CT showed a deviation of the septal veins to the left side. T1-weighted MRI demonstrated a low-intensity mass in the anterior horn of the right lateral ventricle, and T2-weighted image demonstrated the mass as having high intensity. PEG in the sitting position showed no filling of air into the right lateral ventricle due to obstruction of the right foramen of Monro. The patient underwent an operation under a diagnosis of intraventricular benign cyst. The cyst wall was subtotally removed and the right foramen of Monro was opened. Histological examination of the specimen showed an arachnoid membrane with prolific collagen fibers. From an embryological point of view, the arachnoid membrane is derived from the arachnoid cell. We think intraventricular arachnoid cysts to originate from the remnants of the arachnoid cell on the tela choroidea or on the choroid plexus like intraventricular meningiomas. PMID- 2215872 TI - [A case of chronic subdural hematoma associated with idiopathic thrombocytopenic purpura (ITP)]. AB - A 41-year-old male was admitted to our service with right occipital pain as his chief complaint. CT and MRI examinations revealed bilateral chronic subdural hematomas. The patient had also been affected with ITP since the age of 28. Since emergency operation was thought to be dangerous, he was transferred to Tokushima University Hospital, and treated preoperatively by administration of steroids and a large dose of immunoglobulin. When his platelet count had returned to 146,000/mm3, evacuation of the hematoma through burr holes was performed successfully under local anesthesia. The postoperative course was uneventful. So far as we have been able to find in the literature, only 3 cases of ITP complicated by chronic subdural hematoma have been reported. The characteristic clinical feature of these 4 cases including our own case was noted as the absence of a history of trauma. However, the etiological relationship between ITP and chronic subdural hematoma was controversial. Occurrence of chronic subdural hematoma in patients with ITP and in patients under hemodialyzer treatment is very rare. However, intracerebral hemorrhages are rather common among such patients. So it was suggested that the tendency to bleeding among patients with ITP, and among hemodialyzer patients may contribute little as an etiological factor in the evolution of chronic subdural hematoma. PMID- 2215873 TI - [A case of pineal epidermoid cyst showing an interesting magnetic resonance imaging]. AB - A case of pineal epidermoid cyst with interesting findings of magnetic resonance imaging (MRI) is reported referring to the literature. In our case, homogeneous high density area is seen on CT and high signal intensity is recognized on T1 weighted MRI and low signal intensity on T2-weighted MRI. PMID- 2215874 TI - [A case of achondroplasia showing diffuse spinal canal stenosis]. AB - A rare case of achondroplasia showing diffuse spinal canal stenosis is presented. A 39-year-old woman was admitted to our hospital because of numbness of lower extremities and intermittent claudication. The patient's height was 121cm and she had the typical clinical features of an achondroplastic dwarf. Neurological examination revealed spastic paraparesis, and sensory impairment below the level of T11 in the left side and L1 in the right. A plain X-ray feature of the spine showed spinal canal stenosis. The interpedicular distances were short in all vertebrae, and especially more prominent in the caudal lumbar region. The sacrum laid horizontally and the sacral angle was narrower than normal case. Myelography and computed tomographic myelography demonstrated severe stenosis of the subarachnoid space at the level of T9-11. Laminectomy was performed from the inferior half of T9 to T11. The yellow ligaments were prominently hypertrophic and these were removed as far as possible. Postoperatively, the weakness of the lower extremities was improved immediately, but numbness remained. Five months after the operation, she suffered from urinary dysfunction, so further laminectomy from T12 to L5 was performed. Also in this operation, hypertrophic yellow ligament was pathognomonic. Following this operation the patient had a good recovery course and returned to work. PMID- 2215876 TI - Individual variation in line bisection: a study of normal subjects with application to the interpretation of visual neglect. AB - Investigations of left visuo-spatial neglect are reviewed with special reference to line bisection performance. Attention is then drawn to inconsistencies in the direction and magnitude of transection displacements in group studies of normal controls. We argue that the lack of reliable information about normal mechanisms for line bisection makes it impossible to interpret pathological performance in neglect. Accordingly, we report a case-series of 22 normal young adults, each of whom bisects 10 lines of differing lengths 10 times each. There is very substantial between-subject variation in both the magnitude and direction of the linear regression of transection displacement on line length; there are likewise considerable differences in the magnitude of the linear regression of standard deviation on line length. These two sources of individual variation are uncorrelated. We propose a psychophysical theory of line bisection, and suggest that the basic mechanisms responsible for task-performance are qualitatively intact in visuo-spatial neglect, albeit quantitatively impaired. PMID- 2215875 TI - Effect of response programming on hemispheric differences in lexical decision. AB - A lateralized tachistoscopic lexical decision task with concrete nouns and orthographically regular nonwords was administered to normal subjects in three conditions using unimanual responses: Yes-No, Go-NoGo with nonword targets, and Go-NoGo with word targets. There was an overall right visual field advantage in accuracy and sensitivity, an interaction between visual hemifield and wordness in latency, and an overall "word" bias. No effect interacted with experimental conditions, showing that response programming did not affect hemispheric asymmetries. The data suggest independent lexical access and similar response programming in each hemisphere. These results are examined in light of three psycholinguistic models of lexical access and are interpreted to support instead a fourth one which posits separate and parallel computations for word decisions and for nonword decisions in each hemisphere. PMID- 2215877 TI - Cross-modal matching by amnesic subjects. AB - The present study examined the performance of two groups of amnesic subjects on a cross-modal identification task. It was found that subjects with Korsakoff's disease did not differ from alcoholic controls on their ability to match the tactile feel of an arc with the visual appearance of the full circle from which the arc was taken. The postencephalitic subjects were, however, impaired on this same task. All groups performed normally on two intramodal control tasks. The postencephalitic group, like the Korsakoff subjects, were also poor at identifying common objects from tactile cues. The results are consistent with the notion that limbic regions in the temporal lobe are important for cross-modal associations. PMID- 2215878 TI - Immune and autoimmune diseases in dyslexic children. AB - One hundred and five dyslexic and 105 control children were compared for frequency of immune diseases, autoimmune diseases, and non-right-handedness in the light of the Geschwind-Behan (1982) "testosterone hypothesis". The results showed significantly more immune- and autoimmune-diseases int he dyslexic group. There were no differences between the groups in the frequency of non-right handedness. There were no interactions with gender, although there were more non right-handed boys than girls in the total sample. Mothers of children who were dyslexic experienced significantly more negative life-events during pregnancy, they also experienced the pregnancy as more difficult, and they had more spontaneous abortions. In conclusion, the results support some aspects of the "testosterone hypothesis", but they also point to a more complex pattern of interaction between the factors that still remain unanswered. PMID- 2215879 TI - Handedness, clumsiness and developmental language disorders. AB - Hand preference and relative hand skill were assessed in 83 8 1/2-year-olds who had first been enrolled in a longitudinal study of specific language impairment at 4 years of age. There was no evidence that hand preference or relative skill of the two hands differed from normal in this population, although skill of both hands was poor in children with persisting language difficulties. PMID- 2215880 TI - Event-related potential evidence of sex differences in verbal and nonverbal memory tasks. AB - ERPs were recorded from 19 scalp electrodes while 48 subjects (24 females) performed visual recognition tasks for recurring verbal items and recurring abstract figures. Reaction times were longer in the figures than verbal task; the latencies of the ERP components (P2, N4, P3, P4) were also longer for the figures. A nonreversing asymmetry (R greater than L) was seen in both tasks. Significant task by electrode interactions (for P3, P4) were found, due to larger amplitudes anteriorly for the figures, but larger amplitudes posteriorly for the verbal task. All ERP latencies were longer for males than females. There were sex by task by electrode interactions in the amplitudes, due to larger ERPs (P2, N4) for females anteriorly for the figures, but slightly larger posteriorly for the verbal task. These results suggest that sex differences in cognitive abilities may be based on differences in biological mechanisms. PMID- 2215881 TI - Elaborative strategies in word pair learning--DC-potential correlates of differential frontal and temporal lobe involvement. AB - Cortical DC potentials were recorded while subjects were learning word pairs. The use of an elaborative mnemonic strategy resulted in a left frontal sustained negative shift. Its amplitude was independent of whether imagery mnemonics or semantic mnemonics were used. By contrast, posterior temporal potentials differed according to strategy: with imagery mnemonics, subjects had more symmetrical potentials over posterior temporal areas whereas with a semantic strategy, there was a left hemispheric preponderance of the DC potential. An interpretation within Stuss and Benson's theory on the frontal lobes is given. PMID- 2215882 TI - Asymmetries in hand movement during block design construction. AB - Changes in patterns of hand use were examined as a function of task demand characteristics. Using blocks, right- and left-handed male and female subjects were asked to simultaneously construct two replicas of presented patterns, one with each hand. With the presentation of visual-spatial patterns, a shift toward use of the left hand from baseline was observed. This change was least evident among right-handed females. The observed shift in hand use toward the left on a visuo-constructive block design task might suggest differential involvement of the right hemisphere with changes in task demand characteristics. PMID- 2215883 TI - Contrast sensitivity and low spatial frequency discrimination in hemi-neglect patients. AB - Contrast sensitivity for sinusoidal gratings of different spatial frequencies and low spatial frequency discrimination of high contrast squarewave gratings were measured in 26 right brain damaged patients, 15 of whom showed symptoms of spatial hemi-neglect. No difference was present between neglect and non-neglect patients in either task. A difference in contrast sensitivity restricted to low spatial frequencies was present between controls and patients, independent of neglect. Overall, results indicated that spatial vision at threshold and suprathreshold levels is not selectively impaired in patients with hemi-neglect, a finding consistent with theories which postulate a post-perceptual locus of impairment in this syndrome. PMID- 2215884 TI - Comparing the cerebral hemispheres on the speed of spatial shifts of visual attention: evidence from serial search. AB - We compared the speed at which visuo-spatial attention may be shifted from one stimulus to another as a function of the visual hemifield in which the items were displayed in a visual search task requiring serial processing. The increase in response time with the number of items displayed was similar for left- and right hemifield presentations. This suggests that the rate at which visuo-spatial attention can be shifted from one stimulus to another during visual search does not differ between the cerebral hemispheres. PMID- 2215885 TI - Verbal fluency in Parkinson's disease. AB - This study compares the performance of Parkinson's disease patients with age matched controls on semantic and letter-initial verbal fluency tests. An analysis of variance revealed that Parkinsonian patients showed impaired word production. However when the covariates of age, present verbal ability (Mill Hill Synonyms) and severity of depression (Geriatric Depression Screening Scale) were included in an analysis of covariance, the significant effect of Parkinson's disease on verbal fluency disappeared. Instead, age and present verbal ability were revealed to be the significant sources of between subject variation in total verbal fluency performance; results indicated that increased age and lower present verbal ability resulted in poorer performance on the verbal fluency tests. Depression score was not a significant source of between subject variation. The results are discussed in relation to those recently reported by Gurd and Ward (1989). PMID- 2215886 TI - Relationships between the direction of movements and handedness in children. AB - It has been proposed that human handedness can be deduced from the direction of voluntary movements. To test this assumption, children of an elementary school were observed as they performed several tasks with their dominant hand; drawing circles on a piece of paper, making circular movements in the air with their index finger, drawing a human profile, boring and drawing a horizontal line. Both handedness of the children and the directionality of their drawings and movements were assessed. It appeared that the direction of drawing a horizontal line is the only variable that differentiates well between handedness groups. While this variable was hardly influenced by age, other variables were. Circling, for instance, was predominantly clockwise in the youngest and counter-clockwise in the older children. It was argued that the handedness of individual subjects cannot safely be determined from these measures. PMID- 2215887 TI - Differences in feminine and masculine characteristics in women as a function of handedness: support for the Geschwind/Galaburda theory of brain organization. AB - The Geschwind/Galaburda testosterone theory successfully predicted differences in feminine sex role identification and behavior between women with anomalous dominance and standard dominance. The women with anomalous dominance (consisting of left-handed and ambidextrous as well as right-handed women with first-degree non-right-handed relatives) were compared to women with standard dominance (right handed women with all right-handed first-degree relatives) on the Bem Test of Sex Role Identity and a tomboy scale. Across three samples, handedness classifications were related to both tomboy characteristics and sex role identification. In addition, the study showed that the anomalous dominance women had a higher masculine sex role identification as compared to the college normative sample for the Bem, while the standard dominance women had a higher feminine identification than the normative sample. PMID- 2215889 TI - Analysis of "scalp potential fields" and three-dimensional localization of the sources of epileptic activity of the human brain. PMID- 2215888 TI - Electrophysiological investigation of the hippocampal projections to the neurosecretory cells of the supraoptic nucleus of the rat hypothalamus. AB - The impulse activity of antidromically identified neurosecretory cells of the supraoptic nucleus of the hypothalamus of rats in response to stimulation of the ventral hippocampus was investigated. Short-latency phasic excitation reactions were identified, and inhibition reactions were not found. The presence of excitatory synaptic inputs from the hippocampus to other neurons of the nucleus and of the perinuclear zone, which are predominant by comparison with analogous projections to the neurosecretory cells, was demonstrated. The features of limbic hypothalamic relationships are discussed in the context of afferent control of the activity of the neurosecretory cells. PMID- 2215890 TI - Segment-by-segment histological analysis of the cervical division of the spinal cord and of the roots of the spinal nerves and ganglia in severe craniocerebral trauma. PMID- 2215891 TI - Some principles of the organization of the preterminal and terminal ramifications of the afferent conductors in the neuropil of the dorsal ganglia of the edible snail. PMID- 2215892 TI - "Reflexes of purpose and freedom" in the comparative physiology of higher nervous activity. AB - The most complex unconditioned "reflexes of aim and freedom," discovered by I.P. Pavlov, are compared with the "competence drive" and the "motivation of the resistance to coercion," respectively, described by contemporary ethologists. On the basis of the unconditioned "reflex of purpose," conditioned reflexes were developed in which positive emotions arising in connection with the perfection of a skill, irrespective of its pragmatic significance at a given moment, serve as the reinforcement. The unconditioned "reflex of freedom" is regarded as a phylogenetic precursor of the will, and its acute extinction as the physiological mechanism of hypnosis. It was demonstrated experimentally that the appearance of the state of "animal hypnosis" (immobilization catatonia) in rabbits is accompanied by the predominance of electrical activity and heat production in the right hemisphere, i.e., by symptoms which are found in hypnosis in man. PMID- 2215893 TI - Features of the systemic organization of cortical neurons with different forms of the manifestation of a conditioned reflex to time. AB - A conditioned food-procuring reflex to time (2-min interval) was developed in cats. The coupled activity of neurons in microareas and between microareas of the motor cortex was compared by cross correlation analysis in different forms of the manifestations of the conditioned reflex: decrease in the amplitude of respiratory movements, increase in amplitude, and food-procuring movement of the paw for several seconds prior to the delivery of the reinforcement. Differences were manifested in the degree of increase in the number of functional associations in the second half of the interval as compared with the first, and, to a still greater degree, also in the frequency with which intervals were encountered with altered structure of the interrelationship between the neurons. The changes observed did not always correlate with the change in the frequency of impulse activity of individual neurons, which was noted substantially less frequently. PMID- 2215894 TI - Coherence analysis of the electrical activity of the rabbit brain in the process of the formation of the polarization dominant. AB - It has been demonstrated by means of the method of spectral coherence analysis in rabbits, under conditions of a chronic experiment, that when a motor "dominant" reaction is still absent in the early stages of the dominant, interhemispheric asymmetry appears in the Coh spectra of the electrical activity of the sensorimotor cortex and the VPL nucleus of the thalamus. On the other hand, interhemispheric asymmetry appears in the Coh spectra of the electrical activity of the sensorimotor cortex and the CA3 field of the dorsal hippocampus only at the stage at which the motor "dominant" reaction is recorded. The asymmetry in the alpha and beta ranges of the frequencies in the Coh spectra of the biopotentials of the investigated regions, which coincides with the attainment of the motor "dominant" reaction, is associated with the processes of the organization of movement. PMID- 2215895 TI - Influence of dominant motivation on the functional organization of auditory input to the sensorimotor cortex of the cat brain. AB - The results of experiments reviewed in this article demonstrate the possibility of the transformation of the frequency tuning of the auditory input into the sensorimotor cortex (SMC) of the cat under the influence of a dominant motivation. Similar changes took place in the parietal cortex (PC) but they were significantly less in absolute magnitude. The identified transformation of the frequency tuning of the auditory input into the SMC and the PC is in agreement with a change in the biological significance of the auditory signals of kittens for females in the period of lactation, and corresponds for each cat to the spectral composition of the vocalizations of its own kittens. PMID- 2215896 TI - Blood-flow and pO2 in the posterior hypothalamus of cats during paradoxical sleep. AB - It was found in chronic experiments in cats, using the recording of local blood flow and oxygen tension (pO2) in the anterior and posterior hypothalamus in the sleep-wakefulness cycle, that when the phases of sleep are alternated, the changes in these parameters are in different directions: the level of blood flow and the frequency of fluctuation of the pO2 during paradoxical sleep increase in the posterior hypothalamus, while they decrease in the anterior hypothalamus. On the other hand, the opposite pattern is observed during slow-wave sleep. The multidirectionality of the changes in local blood flow level and in the frequency of fluctuations of pO2 in one and the same sleep phase indicate that they are of local origin and must be governed by functional-metabolic shifts in these structures; the functional state of the posterior hypothalamus during paradoxical sleep is assessed on this basis. PMID- 2215897 TI - Electrophysiological analysis of the conditioned reflex activity of cats during thirst. AB - The EEG of the cerebral cortex and the electrohypothalamogram (EHG) was recorded in cats with a salt load and water deprivation during the performance of runs conditioned to non-salty and salty food signals. The non-salty food signal against the background of thirst was accompanied only by the activation of the cerebral cortex, whereas the hypothalamus in addition to the cortex was involved in the activation in relation to the salty food signal. In those cases in which the non-salty signal was reinforced by salty food and the animal has eaten it (although it had rejected it in the presence of thirst), a strong activation of the cortex was observed, with involvement of the paraventricular divisions of the hypothalamus. The remodeling of the signal role of the conditional signals was achieved in accordance with the new quality of the food reinforcement. The hypothalamo-cortical mechanisms of the dominant motivation and its conditioned reflex effectuation are discussed. PMID- 2215898 TI - Influence of extirpation of the sensorimotor area of the cortex on the formation of conditioned reflexes in response to a complex signal in the ontogenesis of the cat. AB - The influence of the extirpation of the sensorimotor cortex (SMC) on the formation and maintenance of a previously developed alimentary conditioned reflex to a simultaneous complex stimulus (light + sound) with extinction of the reaction to unreinforced components of the complex signal was studied in kittens aged 39 days to 4 months. The extirpation of the SMC prior to 2.5 months of age had no influence on either the formation or maintenance of the conditioned reflex to the complex signal developed prior to the operation. The extirpation of the SMC in preliminarily trained kittens aged 3.5 months and older leads to disinhibition of the differential components when the positive conditioned reflex to the complex signal is maintained. In untrained kittens of the same age the extirpation of the SMC was manifested in the animals' incapacity to inhibit the motoric reaction to the differential signal. The question of the role of the SMC in ontogenesis during the formation of adequate forms of behavior which require the achievement of intersensory interactions is discussed. PMID- 2215899 TI - Mapping of normal brain maturation in infants on phase-sensitive inversion- recovery MR images. AB - It is illustrated that phase-sensitive inversion-recovery MR images are particularly well suited for the monitoring of brain maturation and myelination in the neonate and young infant. Provided appropriate timings are applied with the inversion-recovery MR pulse sequence, the myelinated areas show up as bright spots in the phase-sensitive images. The chronology of the appearance, and the location of these hyperintense zones correlate well with the chronology of brain maturation, as assessed by other means. In particular, the progressive functional capabilities of the infant correlate well with the progress of myelination, as exhibited by the MR images. PMID- 2215900 TI - Morphology of cerebral lesions in children with congenital hemiplegia. A study with computed tomography. AB - This study has analysed the results of CT scans of the brains in children with congenital hemiplegia. The material consists of 111 out of a total of 151 children with this cerebral palsy syndrome in a population-based series. We have classified the morphological findings in five groups. The groups are designed to reflect the phase of maturation of the brain when the insult happened. The groups are: 1. Maldevelopment, 2. Periventricular atrophy, 3. Cortical-/subcortical atrophy, 4. Miscellaneous, 5. Normal. In contrast to previous reports we found a high proportion (17%) with maldevelopment. However the dominating morphological pattern was periventricular atrophy, consistent with a hypoxic-ischemic insult to the immature brain, seen in 42%. Cortical and/or subcortical atrophy was found in 12%. Three children (3%) presented with morphological patterns not possible to classify. The group with no pathology according to CT was 26%. PMID- 2215901 TI - MR imaging of spastic diplegia. Comparative study between preterm and term infants. AB - Eighteen children (eleven preterm birth and seven term birth) with clinical evidence of spastic diplegia (SD) were studied to clarify the differences of the lesions between preterm and term SD on MR imaging. All with preterm birth showed similar abnormalities of the periventricular white matter represented by high intensity in T2-weighted imaging and low intensity in T1 imaging. It seemed that the lesions were periventricular leukomalacia (PVL) and dysmyelination pathologically and correlated well clinically with spastic diplegia. SD with term birth group showed various lesions, two brain anomalies (schizencephaly and corpocephaly), one PVL, four showed no lesions. We suggested that SD with preterm birth is not only a clinical but also a pathological entity. PMID- 2215902 TI - MR imaging of wallerian degeneration in the human brain stem after ictus. AB - Magnetic resonance (MR) imaging of wallerian degeneration in the brain stem was studied in 30 hemiplegic patients within 12 months of ictus. As early as 25 days after the ictus, decreased signal intensities on proton-density(PD)-weighted images were observed in the brain stem ipsilaterally. This hypointensity gradually approached an isointense stage during 70-80 days after the ictus, abnormal intensities were not detected in any pulse sequence. We termed this phenomenon "Fogging effect of wallerian degeneration". In later stages, at least 81 days after the ictus, increased signal intensities on T2-weighted images, with or without decreased signal intensities on T1-weighted images, were observed in the brain stem, ipsilaterally. Finally, at least six months after the ictus, mild shrinkage of the ipsilateral brain stem was newly detected on the T1-weighted images. MR imaging has proven to be a sensitive diagnostic modality for evaluating wallerian degeneration in the brain stem. PMID- 2215903 TI - Does the washout phenomenon of Tc-99m HM-PAO correlate to the "filling-in" phenomenon of I-123 IMP with brain SPECT? AB - Using SPECT, the time course of brain uptake was compared between N-isopropyl-p [I-123]-iodoamphetamine (I-123 IMP) and Tc-99m d,l hexamethyl-propyleneamine oxime (Tc-99m HM-PAO). Of 14 patients with cerebrovascular disease showing areas of the "filling-in phenomenon" (i.e. delayed uptake) with I-123 IMP brain SPECT, 7 exhibited persistent defects with Tc-99m HM-PAO (Group I), and 7 showed early washout after the initial uptake (Group II). The filling-in of I-123 IMP did not always correlate to the washout region of Tc-99m HM-PAO. The temporal changes were also confirmed by semiquantitative analysis. While the filling-in of I-123 IMP was affected by many factors, the washout of Tc-99m HM-PAO was attributed to significant reduction of Tc-99m HM-PAO in the plasma. Delayed imaging of the brain with Tc-99m HM-PAO using SPECT may give a more accurate estimate of regional cerebral blood flow in cerebrovascular disease, because it should be lees effected by cerebral blood volume. PMID- 2215904 TI - Putaminal hemorrhage: clinical-computed tomographic correlations. AB - Ninety-two percent of 100 patients with putaminal hemorrhage were hypertensive. Of the eight normotensive patients, seven were substance abusers or had bilateral putaminal hemorrhages. The one other normotensive patient was less than 40 years old. The 100 hemorrhages had the following locations: 1. medial putaminal (17 cases; six were normotensive and less than 40 years old and five were substance abusers); 2. lateral putaminal extending through the external capsule (eleven cases); 3. putaminal-capsular and subcortical white matter (32 cases); 4. putaminal cerebral hemispheric (19 cases); 5. putaminal-thalamic (19 cases); 6. bilateral (two cases). A disproportionate number of black patients suffered hematoma extension to the cerebral hemispheres or thalamus (46%) compared to Caucasians (23%). Overall mortality was 20% (17 blacks and three Caucasians) and occurred in patients with hematoma extension to the thalamus or cerebral hemispheres. Contrast-enhanced CT was performed in all 100 patients and provided no additional diagnostic yield. This indicates limited use for enhanced CT in hypertensive patients with putaminal hemorrhage who have a characteristic appearance of the acute hemorrhage on the nonenhanced CT. PMID- 2215905 TI - Multiple cerebral arteriovenous malformations (AVMs). Review of our experience from 203 patients with cerebral vascular lesions. AB - From our series of 203 patients with cerebral vascular lesions, 18 (9%) could be included in the multiple arteriovenous malformation category. There were five patients with Rendu-Osler-Weber, one with Wyburn-Mason syndromes and two with concurrent arteriovenous malformations. The remaining ten patients (4%) had multiple brain arteriovenous malformations. Careful angiography with magnification is necessary to try to diagnose multiple brain AVMs, since these sometimes become apparent only after embolization of a larger dominant AVM. The incidence of multiple brain arteriovenous malformations is likely to have been underestimated due to the failure to recognize micro-arteriovenous malformations associated with larger arteriovenous malformations. PMID- 2215906 TI - Cranial MRI in Wilson's disease. AB - Thirty-eight patients with biochemically proven Wilson's disease underwent magnetic resonance-imaging (MRI) of the brain as well as neurological examinations. The patients were scanned using spin-echo (SE) sequences; the neurologist was looking for typical symptoms: dysarthria, tremor, ataxia, rigidity/bradykinesia and chorea/dystonia. Pathological MR findings believed secondary to this uncommon inherited disorder of copper metabolism were found in twenty-two subjects. Focal abnormalities were seen in the lenticular, thalamic and caudate nuclei as well as in brain stem and white matter; these lesions were best demonstrated on T2-weighted sequences as hyperintense areas. In eight patients we found diffuse brain atrophy with consecutive widening of the ventricular system. Five subjects showed mild, nineteen severe neurologic deficits. Generally there was no correlation between MR findings and clinical neurological symptoms; the impairment of cell-metabolism causing functional alterations of the brain precedes morphological changes. During treatment with the copper chelator D-penicillamine there seemed to be a phased course of disease. Shortening of T1-relaxation due to paramagnetic influence of copper was not seen; a possible explanation could be intracellular deposition--a proton electron-dipolar-dipolar-interaction would therefore be impossible. PMID- 2215907 TI - Regression of an internal carotid artery pseudoaneurysm after therapeutic embolization of a post-traumatic carotid-cavernous fistula secondary to gunshot injury. AB - A case is reported of a 53-year-old woman who was hit by a bullet which penetrated the skull base and caused a left carotid-cavernous fistula of the direct type and a pseudoaneurysmal dilation of the high cervical portion of the left internal carotid artery. The fistula was successfully embolized by positioning a balloon into the fistula itself by means of the Debrun technique: unexpectedly the size of the pseudoaneurysm decreased after the embolization; the possible explanations for this event are discussed. PMID- 2215908 TI - Pseudoaneurysm of the cervical internal carotid artery with associated hypoglossal nerve paralysis. Demonstration by CT and angiography. AB - A case of pseudoaneurysm of the cervical internal carotid artery with associated hypoglossal nerve paralysis resulting from trauma is presented. CT and angiographic manifestations of this pseudoaneurysm and the resulting hypoglossal nerve paralysis are discussed. Correlative CT and angiographic findings of this association have not previously been described in the literature. PMID- 2215909 TI - Focal pachygyria with unusual vascular anomaly. AB - A case of focal pachygyria with an unusual vascular anomaly is reported. Preoperative magnetic resonance imaging demonstrated few and broad gyri, and an abnormally thickened cortex of the right frontal lobe. In addition, T2-weighted imaging showed a high intensity lesion beneath the thickened cortex. In the pachygyric cortex, the peripheral portions of the arteries were tortuous and irregularly dilated, and prominent deep medullary veins were found draining into the subependymal veins. Histological examination revealed a decreased number of neurons with no tendency towards lamination, and degenerative changes with gliosis in the white matter. These findings suggest that the etiology of this anomaly may be gradual perfusion failure restricted to the territory of the anomalous vessels through the period of neuronal migration to the post-migratory, perinatal stage. PMID- 2215910 TI - Neurinoma of the jugular foramen. PMID- 2215911 TI - Magnetic resonance imaging of an intraventricular craniopharyngioma. AB - A case of a craniopharyngioma confined entirely to the third ventricle is reported. MRI revealed an isointense and high signal lesion on T1- and T2 weighted images, respectively, with homogeneous enhancement by Gd-DTPA. The tumor was reduced by 90% in 4 months after 60 Gy radiation therapy. Intraventricular craniopharyngioma is unusual and is not associated with tumoral calcification or cyst formation. PMID- 2215912 TI - Primary myxoma of the posterior fossa. AB - A rare case of primary intracranial myxoma of the posterior fossa is described in a 32-year old woman. The patient presented with a history of headaches, disequilibrium, nausea and abnormal vision for several months. Computed tomography (CT) showed a well-demarcated hypodense mass. After contrast administration the mass appeared as an inhomogeneously enhancing lesion surrounded by a small rim of edema. The mass was surgically excised with histological examination revealing a true myxoma. Echocardiography revealed no evidence of a cardiac myxoma. The CT appearance of other case reports of non cardiac myxomas in the literature is reviewed. PMID- 2215913 TI - Cerebral atrophy in Lyme disease. PMID- 2215914 TI - The thresholds of the jaw-opening reflex and trigeminal brainstem neurons to tooth-pulp stimulation in acutely and chronically prepared cats. AB - Electrical stimuli were applied to tooth-pulp in cats and the thresholds of the jaw-opening reflex and of neurons in the trigeminal sensory nuclei were determined. The effects of the method of preparation of the animal for stereotaxic recording were determined by making observations on animals set up in one of three ways: acutely in the usual manner; chronically, three to five days before recording; and acutely with precautions to minimize nociceptive input to the central nervous system. The threshold of the jaw-opening reflex increased progressively during the setting up of the normal, acute preparations and at the time brainstem recording began was significantly higher in these than in either the chronic or low-trauma acute preparations. Previous studies have shown that the increase in threshold is maintained for several hours and is not due to the effects of the anaesthetic. In normal acute preparations, few units (27/154) were found that had thresholds below 50 microA, 0.1 ms, whereas many units were encountered that responded to such a stimulus in chronic (147/152) and low-trauma acute (99/127) animals. In the chronic and in low-trauma acute preparations, there was no significant difference between the thresholds of the units in the main sensory trigeminal nucleus and spinal subnucleus oralis compared with those in subnucleus caudalis. Thus the preparation of an animal for stereotaxic recording can cause a severe and long-lasting depression in the excitability of neurons in the trigeminal sensory nuclei and an increase in the threshold of the jaw-opening reflex. This effect will have influenced the results of previous studies on the responses evoked in central neurons by stimulation of tooth-pulp, and may have similarly affected recordings from other regions. PMID- 2215916 TI - Neurotoxic effects of L-alpha-aminoadipic acid on the carp retina: a long term observation. AB - The hypothesis has been tested that the enantiomers of alpha-aminoadipic acid have different target effects; the L-isomer has both glio- and neurotoxic actions, while the DL-isomer has a gliospecific action in the CNS. Electrophysiological and morphological studies were carried out on the retina of the carp (Cyprinus carpio) for one to two months after intraocular injection with alpha-aminoadipic acids at various doses. Intracellular recording from horizontal cells and extracellular recording of spike discharges from ganglion cells in isolated retinal preparations were made from control and pretreated retinas at various intervals after intraocular injection with the enantiomers. In control retinas, application of 15 mM L-alpha-aminoadipic acid in the superfusate resulted in hyperpolarization of all horizontal cells and in a decrease in amplitude of their light responses (S-potentials). In the retinas pretreated with L-alpha-aminoadipic acid (8 mumol), low amplitude S-potentials were seen during an early phase 2-4 h after ocular injection, but the normal appearance of S potentials was restored one day after injection. In control retinas, a brief period of iontophoretic application of L-alpha-aminoadipic acid resulted in a slight activation of the spontaneous spike firing of ganglion cells but a slight decrease in the rate of light-induced firing. In retinas pretreated with intraocular L-alpha-aminoadipic acid (4 mumol) 4 h prior to eye removal, however, light-induced spike discharges were abolished from nearly all spontaneously firing ganglion cells (greater than 90%). Their unresponsiveness to light stimuli lasted for more than two months after injection, and was accompanied by insensitivity to iontophoretically applied putative neurotransmitters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2215915 TI - Organization of radial glia and related cells in the developing murine CNS. An analysis based upon a new monoclonal antibody marker. AB - A monoclonal antibody, RC1, has been generated which provides a selective and sensitive immunohistochemical marker of radial glial cells and related cell forms during development of the mouse CNS. Beginning on embryonic day E10, immunocytochemistry performed on cryostat sections stains throughout the CNS a subpopulation of cells in the ventricular zone with radial processes that terminate with endfeet at the pial surface. These processes become fasciculated and attain maximal densities by E12-14 in the spinal cord and lower brainstem and by E14-16 in the midbrain, cerebellum and forebrain. Fasciculation is especially prominent for a subclass of these cells at the midline of the brainstem and spinal cord. As nuclear and cortical structures develop, the trajectories of the radial fiber fascicles undergo systematic and region-specific distortions in their initially simple linear configuration, in the process maintaining a consistent spatial registration of germinal ventricular zones with distal sites of assembly of post-migratory neurons. In the late fetal period, radial glial progressively disappear and scattered immature astrocytes bearing multiple fine processes appear in most regions of the CNS. In the spinal cord, a transitional unipolar radial form is identified in the emerging ventral and lateral funiculi between E13 and E17. In the cerebellum, precursors to the unipolar Bergmann glial cell are identified by E15, and in the retina, precursors of the bipolar Muller cell are identified by E16. Postnatally, RC1-stained radial glia become sparse, and after one week, immunoreactive cells include only ependymal cells, hypothalamic tanycytes, Bergmann glia, Muller cells, a unipolar radial form in the dentate gyrus, and a subpopulation of white matter astrocytes. These results suggest that radial cells of astroglial lineage comprise a diverse set of cell classes which subserve multiple functions in the developing and adult brain. PMID- 2215918 TI - Subpopulations of corticotropin-releasing hormone neurosecretory cells distinguished by presence or absence of vasopressin: confirmation with multiple corticotropin-releasing hormone antisera. AB - Parvocellular corticotropin-releasing hormone neurosecretory cells in the hypothalamic paraventricular nucleus project axons to the portal capillary plexus in the external zone of the median eminence. Immunocytochemical studies have identified two approximately equal subpopulations of these corticotropin releasing hormone neurons in normal rats, distinguished by the presence or absence of co-existent vasopressin, and different responses to stress. However, it was recently proposed that the vasopressin deficient cells do not contain corticotropin-releasing hormone, but have been misidentified due to cross reactivity of the corticotropin-releasing hormone antiserum to peptide histidine isoleucineamide. It is shown here that the same set of corticotropin-releasing hormone neurons (including both vasopressin expressing and vasopressin deficient subtypes) was labeled with multiple corticotropin-releasing hormone antisera. These included two antisera that did not cross-react with peptide histidine isoleucineamide: one against ovine corticotropin-releasing hormone, and one rat corticotropin-releasing hormone antiserum absorbed with peptide histidine isoleucineamide. The results provide further support for the hypothesis of functionally distinct compartments of the corticotropin-releasing hormone neurosecretory system that can modulate the ratio of vasopressin to corticotropin releasing hormone in portal blood. PMID- 2215917 TI - Pattern adaptation in cat visual cortex is a co-operative phenomenon. AB - The effects of microiontophoretic application of glutamate, GABA and the GABA antagonist, bicuculline methiodide were tested on the degree of adaptation exhibited by striate cortical cells to moving sin wave grating patterns. Application of GABA, which prevents firing of the cell and thereby any fatigue of the cell, did not reduce the degree of adaptation. Administration of either glutamate or GABA, without simultaneous exposure to the adapting high-contrast gratings did not reduce the sensitivity of the cell to subsequent exposure of a low-contrast grating, showing that adaptation is not caused by the excitatory or inhibitory activity of the cell itself. Application of the GABA antagonist, bicuculline did not prevent pattern adaptation, indicating that the lowered sensitivity of the cell is not mediated by a GABAergic inhibition acting on the cell. Thus adaptation of a striate neuron is not due to altered sensitivity of the cell to a constant input but depends upon changes in the input itself. It is most likely that these changes occur in a co-operative cortical network, whose effect on individual cortical cells is mediated by intracortical excitatory connections. PMID- 2215920 TI - Fine structural changes in the superior cervical ganglion of adult rats after long-term administration of baclofen, a GABAB receptor agonist. AB - The aim of the present study was to examine the fine structural changes in the superior cervical ganglion of adult rats following baclofen treatment. On the addition of this GABAB receptor agonist there was a transient increase in the number of coated vesicles and pits in the dendrites of principal sympathetic neurons. As compared to the control ganglia, we found a significantly higher number of synapses which had coated pits attached to the postsynaptic densities. In interpreting these observations it is suggested that the GABAB receptors play some role in mediating the synaptogenetic action of GABA, although the formation of vacant postsynaptic densities and spines was not seen after baclofen treatment. PMID- 2215919 TI - Ontogeny of the neuronal intermediate filament protein, peripherin, in the mouse embryo. AB - The expression of peripherin, a type III neuron-specific intermediate filament protein, and the middle neurofilament subunit were studied in the mouse embryo using immunofluorescence staining. The earliest staining for both proteins is seen at embryonic day 9 in the myelencephalon, initially as fiber staining followed by cell body staining in the developing facial and acoustic nuclei. As the embryo develops, there is rostral as well as caudal extension of peripherin and staining is seen in the trigeminal ganglia, nerve fibers and in the enteric nervous system. As the spinal cord forms there is anti-peripherin staining in developing motoneurons of the anterior horns while little cell body staining is seen for the middle neurofilament subunit. Both antibodies stain the developing dorsal root and its entry zone, but peripherin is found in the secondary sensory and commissural fibers while the middle neurofilament subunit is not. While both proteins are found in the neurons of the dorsal root ganglia, their distribution varies. The larger peripheral cells of the ganglia contain both proteins while the smaller more central cells, constituting over 60% of the cells in the ganglia, contain only peripherin. A similar picture is found in the sympathetic ganglia where there are cells which contain peripherin. middle neurofilament subunit or both, but where the majority of the neurons have only peripherin in their cell bodies. Peripherin is not found in the developing retina or in the adrenal medulla. Peripherin is also completely absent from cell bodies in the cerebral and cerebellar cortices. These results indicate that peripherin is found in development only in regions in which it is found in the adult. It can either co-exist with neurofilaments in the same neuron or the two may be independently expressed. PMID- 2215921 TI - Continuous presence of nerve growth factor is required for maintenance of cholinergic septal neurons in organotypic slice cultures. AB - In co-cultures of rat septum and hippocampus, cholinergic neurons, identified by immunocytochemical techniques using antibodies against choline acetyltransferase, were found to be exclusively located in septal tissue. The presence of nerve growth factor during the entire growth period of four weeks increased the activities of acetylcholinesterase and choline acetyltransferase about 10-fold and strongly increased the number of acetylcholinesterase-positive neurons. Application of nerve growth factor yielded different effects depending on the age of the cultures. During the first two weeks in vitro, nerve growth factor enhanced the number of acetylcholinesterase-positive neurons, an effect which was no longer observed following later applications of nerve growth factor. Nerve growth factor increased the activities of cholinergic enzymes during all phases of in vitro development, but the effects of one-week applications were always considerably smaller than those observed following continuous application of nerve growth factor. The results of different application schedules suggest that the continuous presence of nerve growth factor is needed for maximal increases in cholinergic enzyme activities and maintenance of cholinergic neurons in septohippocampal co-cultures. PMID- 2215922 TI - Transected spinal cords grafted with in situ self-assembled collagen matrices. AB - The purpose of this work was to evaluate if the implantation into the gap of a transected spinal cord of a biomaterial providing a scaffolding structure for tissue ingrowth would favor the permeation and the growth of regenerating axons across the spinal-bioimplant interface. The interstump gap of rat transected spinal cords was injected with an ice-cold neutral solution of collagen, either alone or mixed with glyoxal, a harmless tanning agent. Upon warming to the temperature of the tissue, the fluid implant self-assembled forming a loose fibrillar network which simultaneously re-established a physical continuity to the transected organ. At various post-implantation timepoints, the bioimplants were studied by light microscopy, with the picrosirius-polarization method and with scanning electron microscopy. We observed that the bioimplants evolved following three overlapping phases: first a massive inflammatory response characterized by the invasion of cells of heterogeneous nature, then, a phase where microcysts predominated and during which, there is a major remodeling of the biomatrix by the deposition of newly synthesized collagen and of a periodic acid Schiff-positive material. Finally, a regeneration phase occurred where astroglial processes followed by regenerating axons invaded the biomatrix. Three months after implantation, spinal axons had grown from the two spinal stumps and penetrated the bioimplant across at least one lesion interface. However, the glyoxal-tanned collagen matrices showed a better biostability and durability than collagen alone. We conclude that the histopathological reaction of the mammalian lesioned spinal cord, when adequately directed by a scaffolding structure can be beneficial for the expression of the intrinsic regenerative capacity of the spinal cord tissue. PMID- 2215924 TI - Changing patterns of c-fos induction in spinal neurons following thermal cutaneous stimulation in the rat. AB - Patterns of neuronal activity in the lumbar spinal cord of the anaesthetized rat were mapped by immunocytochemical localization of the c-fos gene product, Fos protein, at different timepoints following brief noxious stimulation of one hindpaw (20 s immersion in water at 52 degrees C). After 2 h, Fos-immunoreactive neurons were seen mainly in the superficial laminae of the ipsilateral dorsal horn, with maximum somatotopic organization in lamina II. Subcutaneous injection of dilute formalin produced a similar pattern of immunostaining at 2 h, with a greater proportion of Fos-positive neurons in laminae III-VIII than with heat. With a survival time of 8 h following formalin injection, Fos immunoreactivity was virtually absent from the spinal cord. Eight hours after heat stimulation, however, the superficial pattern had given way to the appearance of a population of immunoreactive cells in the deeper laminae. The pattern of this "second wave" of heat-induced Fos-positive cells had a marked contralateral component, and was still present after 24 h, having become even more diffuse and symmetrical. The number of Fos-positive cells seen at 8 h was increased by local anaesthetic blockade of the peripheral nerve after stimulation, and reduced by continuous barbiturate anaesthesia. These findings suggest that the early stages of thermal injury trigger a complex pattern of molecular events within the spinal cord, which are initially monosynaptic and closely related to primary afferent terminal depolarization, and in the longer term the result of an induced pattern of synaptic activity set up within the spinal cord. PMID- 2215923 TI - Topographical localization of neurons containing parvalbumin and choline acetyltransferase in the medial septum-diagonal band region of the rat. AB - The normal morphology and distribution of parvalbumin-containing neurons (shown in a previous study to be GABAergic nerve cells) of the medial septal-diagonal band region of the adult rat brain have been studied, and the findings compared with observations on choline acetyltransferase-immunoreactive neurons. The two antigens were visualized either in the same sections using a double-label immunohistochemical procedure for the simultaneous localization of parvalbumin and choline acetyltransferase, or in immediately adjacent sections. In double stained sections of the whole medial septal-diagonal band complex, about 34% of the total neurons showed immunoreactivity to parvalbumin; the proportion of parvalbumin-labelled neurons was slightly higher in the medial septal-vertical limb of the diagonal band region, and much lower in the horizontal limb of the diagonal band region. The distribution of parvalbumin- and choline acetyltransferase-containing neurons also varied markedly between different mediolateral subdivisions of the medial septum: about 30, 65 and 2% of the parvalbumin-immunoreactive neurons were present in the midline, medial and lateral part of the medial septum, respectively. At different rostrocaudal levels, the proportion of parvalbumin- and choline acetyltransferase-positive neurons varied in a consistent manner, and the largest number of parvalbumin containing neurons was found at the level 1.9 mm anterior to the bregma. In the absence of reliable immunocytochemical methods for the localization of glutamate decarboxylase and GABA, parvalbumin may serve as a good marker for studying the distribution of GABAergic neurons in the medial septum-diagonal band region. Moreover, the precise maps reported in the present study of the topographic localization of parvalbumin-containing GABAergic and choline acetyltransferase immunoreactive cholinergic nerve cells in the medial septal-diagonal band complex will serve as a useful guide in future morphological and electrophysiological studies on the septum and its efferents. PMID- 2215925 TI - The brain and the immune system: an intact immune system is essential for the manifestation of withdrawal in opiate addicted rats. AB - Gamma irradiation (500 rad) is often used to suppress the immune system in mice, rats and man. Recently, it was shown that irradiation prior to chronic morphine treatment, dramatically reduces the severity of naloxone-precipitated withdrawal in morphine-dependent animals. In the present study adoptive transfer of 2-6 x 10(8) splenocytes to irradiated rats prior to chronic morphine treatment restored the severity of all withdrawal signs precipitated by naloxone. In contrast, adoptive transfer of fractionated splenocyte subpopulations only partially restored withdrawal severity; and transfer of irradiated splenocytes, red blood cells or diluted numbers of normal splenocytes did not have any observed restorative effect. These findings suggest that specific cellular activities or factors derived from lymphoid cells are required for the expression of opiate withdrawal. PMID- 2215926 TI - Cerebellotectal pathways in the macaque: implications for collicular generation of saccades. AB - The cerebellum is thought to modulate saccadic activity in the primate in order to maintain targeting accuracy, and the cerebellotectal pathway has been posited to play a role in this modulation. However, anatomical descriptions of this pathway in primates are sketchy and conflicting. To determine whether the organization of the cerebellotectal projection in primates is similar to that found in other species, neuroanatomical tracer transport techniques were utilized in two species of macaque monkey to label cerebellotectal somata and fiber terminations. Two pathways were found. One, the fastigiotectal pathway, is derived from cells in the caudal fastigial nucleus and projects bilaterally to the rostral end of the intermediate gray layer. The other pathway is derived from cells in the posterior interposed nucleus and the adjacent posterior wing of the dentate nucleus, and it terminates contralaterally throughout the ventral half of the intermediate gray and the deep gray layers. Both of these pathways terminate within the layers of the superior colliculus containing premotor, saccade-related neurons, but the differences in the distribution of their terminals and cells of origin suggest that these two pathways have different functions. Furthermore, the pattern of connections of these two pathways indicates that they do not function as a traditional feedback circuit. We suggest that the cerebellotectal pathways may instead modulate collicular activity in a more complex manner. For example, it may provide signals necessary for corrective saccades or for maintaining spatial registry between the different sensory representations supplied to the superior colliculus and its presaccadic output, which is organized into a motor map. PMID- 2215927 TI - Acetylcholine release in the rat hippocampus as studied by microdialysis is dependent on axonal impulse flow and increases during behavioural activation. AB - Changes in extracellular levels of acetylcholine and choline in the hippocampal formation were measured using intracerebral microdialysis coupled to high performance liquid chromatography with post-column enzyme reaction and electrochemical detection. Various pharmacological and physiological manipulations were applied to awake unrestrained normal rats and rats subjected to a cholinergic denervation of the hippocampus by a complete fimbria-fornix lesion (1-2 weeks previously). Low baseline levels of acetylcholine (about 0.3 pmol/15 min sample) could be detected in the absence of acetylcholinesterase inhibition in all animals. However, in order to obtain stable and more readily detectable levels, the acetylcholinesterase inhibitor neostigmine was added to the perfusion medium at a concentration of 5 or 10 microM and was used during all subsequent manipulations. Addition of neostigmine increased acetylcholine levels approximately 10-fold (to 3.7 pmol 15 min) in the normal rats, which was about 4 fold higher than the levels recovered from the denervated hippocampi. Depolarization by adding KCl (100 mM) to the perfusion fluid produced a 3-fold increase in the extracellular acetylcholine levels, and the muscarinic antagonist atropine (3 microM) resulted in a 4-fold increase in the normal rats, whereas these drugs induced only small responses in the denervated rats. Neuronal impulse blockade by tetrodotoxin (1 microM) resulted, in normal rats, in a 70% reduction in extracellular acetylcholine levels. Sensory stimulation by handling increased acetylcholine levels by 94% in the normal rats, whereas this response was almost totally abolished in the denervated hippocampi. Behavioural activation by electrical stimulation of the lateral habenula resulted in a 4-fold increase in acetylcholine release in normal animals, and this response was totally blocked by a transection of the lateral habenular efferents running in the fasciculus retroflexus. The levels obtained by lateral habenula stimulation were reduced by about 95% in the rats with fimbria-fornix lesions. Following an acute knife transection of the fimbria-fornix performed during ongoing dialysis, acetylcholine levels dropped instantaneously by 70%, indicating that the extracellular acetylcholine levels in the hippocampus are maintained by a tonic impulse flow in the septohippocampal pathway. The extracellular levels of choline were reduced by about 30% after the addition of neostigmine in the normal rats, and increased by about 50% in both normal and denervated rats after addition of KCl to the perfusion fluid. No changes could be detected after atropine, handling, lateral habenula stimulation, or acute fimbria-fornix or fasciculus retroflexus transection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2215928 TI - Membrane properties of interneurons in stratum oriens-alveus of the CA1 region of rat hippocampus in vitro. AB - The membrane properties of interneurons situated near the border of stratum oriens and the alveus of the CA1 region were examined with intracellular recording and staining in rat hippocampal slices in vitro. Cellular staining with Lucifer Yellow indicated that the somata of these interneurons were multipolar and their dendrites projected horizontally along the alveus and vertically toward stratum lacunosum-moleculare. Intrinsic properties (input resistance, action potential amplitude, time constant) and spike after-potentials were typical of non-pyramidal cells. Action potential duration, however, was of relatively medium duration (1.15 ms) and slow afterhyperpolarizations followed depolarization induced trains of action potentials. Spontaneous activity of interneurons was prominent and of either of two types: single action potentials or high frequency bursts of action potentials. Interneurons displayed marked, voltage- and time dependent inward rectification and anodal break excitation. Analysis of the slope of the charging function of hyperpolarizing transients, suggested that these interneurons were electrically compact (dendrite to soma conductance ratio, p approximately 2.7; and electrotonic length constant, L approximately 1.1). Characteristically, interneurons sustained high frequency repetitive firing during long depolarizing pulses. The slope of the frequency-current relation was 442 Hz/nA for the first interspike interval and 117 Hz/nA for later intervals (no. 60), suggesting the presence of spike frequency adaptation. Physiologically, these interneurons resembled more closely basket cells of stratum pyramidale than stellate cells of stratum lacunosum-moleculare. PMID- 2215930 TI - Quantitative autoradiographical analysis of the age-related modulation of central dopamine D1 and D2 receptors. AB - Quantitative autoradiography of [3H]SCH 23390 and [3H](-)-sulpiride binding was performed in the brain of rats of various ages (3, 11 and 24 months) in order to study the changes in D1 and D2 receptor density with age. Binding of [3H]SCH 23390 in the caudate-putamen decreased progressively and markedly at rostral levels in 11- and 24- compared with 3-month-old rats (max. decrease -63%) while at caudal levels significant decrease was observed only in 24-month-old rats. [3H](-)-Sulpiride binding progressively decreased during aging in the caudate putamen at rostral levels and the decrease was more pronounced laterally (-70% at 24 months), while at caudal levels no significant decrease was observed. D1 and D2 binding sites also decreased in the nucleus accumbens and olfactory tubercle of aged rats, while in the substantia nigra only the D1 receptors appeared to be modified with aging. No change was found in the entopeduncular nucleus, amygdala, frontoparietal, suprarinal-prefrontal and anterior cingulate cortex. The results indicate that the age-associated decrease of D1 and D2 receptors is not widespread, being confined to dopaminergic areas with high density of dopamine receptors. PMID- 2215929 TI - Immunocytochemical localization of cholinergic terminals in the region of the nucleus basalis magnocellularis of the rat: a correlated light and electron microscopic study. AB - The cholinergic circuitry in the nucleus basalis magnocellularis of the rat was investigated in a correlated light and electron microscopic study by using monoclonal antibodies against the acetylcholine-synthesizing enzyme, choline acetyltransferase, following the unlabelled antibody peroxidase-antiperoxidase immunocytochemical procedure. After the immunocytochemical approach, large cholinergic cells and a few immunoreactive fibres exhibiting a varicose appearance, were detected by light microscopy in portions of the nucleus basalis magnocellularis located within the anatomical limits of the globus pallidus, mostly in its ventromedial part. Cholinergic neurons and fibre-like structures were also found within the substantia innominata on the edge of globus pallidus. The same material studied by light microscopy was analysed with the electron microscope. At the ultrastructural level, the immunopositive neurons showed the same cytological characteristics and pattern of synaptic input as cholinergic basal forebrain cells. Additionally, scarce immunoreactive preterminal axons and terminal boutons were detected in the region. The immunoreactive terminals were scattered or formed occasional clusters and appeared as heavily immunostained vesicle-filled boutons making exclusively axodendritic synaptic contacts principally with immunonegative distal dendrites. Both symmetric and asymmetric synaptic contacts established between these structures were detected, although the symmetric contacts were the more numerous. The surface of postsynaptic immunonegative dendrites in asymmetric synaptic contact with immunoreactive terminals was generally covered by terminals that lacked detectable immunoreactivity. In contrast, those in symmetric synaptic contact with labelled terminals showed much sparser input from immunonegative terminals, suggesting that they may belong to interneurons. Very rarely, cholinergic terminals were detected in asymmetric synaptic contact with dendrites which also contained positive immunoreaction product. Asymmetric contacts were frequently characterized by the presence of subjunctional dense bodies. The detection of cholinergic terminals in the region of the nucleus basalis magnocellularis of the rat indicates that this region not only contains cholinergic projecting neurons, but receives a cholinergic input itself. Results of this study provide evidence of the existence of a cholinergic transmission in the basal forebrain of the rat, and also that acetylcholine might play a role in the regulation of the extrinsic cortical cholinergic innervation. The possible sources of this innervation are discussed. PMID- 2215931 TI - Uptake and metabolism of [3H]choline mustard by cholinergic nerve terminals from rat brain. AB - The objective of this study was to measure the uptake and metabolism of [3H]choline mustard aziridinium ion in rat brain synaptosomes. In previous investigations, we showed that this compound binds irreversibly to the choline carrier thereby inhibiting choline transport into nerve terminals; it also acts as both a substrate and inhibitor of the acetylcholine biosynthetic enzyme choline acetyltransferase. We now report that [3H]choline mustard aziridinium ion was transported into purified rat brain synaptosomes by a hemicholinium-sensitive mechanism, but at only a fraction of the rate of uptake of [3H]choline. Following 5 min incubation with the nerve terminal preparation, uptake of [3H]choline mustard aziridinium ion was 20% of that of [3H]choline transport, but this fell to 10% of [3H]choline accumulation at 30 min incubation. Apparent Michaelis constants derived from double reciprocal plots of velocity of transport versus substrate concentration revealed that the apparent affinity constants (Km) of the high-affinity choline carrier for [3H]choline mustard aziridinium ion and [3H]choline were not different (1.44 +/- 0.15 and 2.14 +/- 0.80 microM for choline and choline mustard aziridinium ion, respectively). Increasing the incubation time from 5 to 30 min, during which time a proportion of the high affinity choline carriers were irreversibly inactivated by choline mustard aziridinium ion, did not alter the binding affinity for this compound. The maximum velocity of transport (Vmax) for the two compounds were significantly different with the maximum uptake of [3H]choline mustard aziridinium ion being 19.5% of that for choline at 5 min incubation, and falling to only 10.6% of the maximum rate of choline transport by 30 min incubation. [3H]Choline mustard aziridinium ion transported into synaptosomes on the high-affinity choline carrier was metabolized, with 27% being recovered as [3H]acetylcholine mustard aziridinium ion, 27% as [3H]phosphorylcholine mustard aziridinium ion, 7% as unmetabolized [3H]choline mustard aziridinium ion and 16% recovered as an unidentified metabolite. In parallel samples, [3H]choline taken up into synaptosomes was recovered as [3H]acetylcholine (71%) and unmetabolized [3H]choline (18%) with no net production of [3H]phosphorylcholine. Acetylation of [3H]choline mustard aziridinium ion amounted to only 7.6% of [3H]acetylcholine synthesized under the same conditions. These results show clearly that choline mustard aziridinium ion was accumulated into the cholinergic nerve terminals by the high-affinity choline carrier, but the amount was small relative to the uptake of choline and probably restricted by progressive inactivation of the transporters through covalent bond formation. PMID- 2215933 TI - Sensory responses of caudal trigeminal neurons to thermal and mechanical stimuli and their behavioural correlates in the rat. AB - Behavioural experiments in the freely moving rat were carried out to determine thermal and mechanical nociceptive thresholds to ramp stimuli applied to the face. The mean thermal escape threshold was 43.5 degrees C, and the mean mechanical escape threshold was 179.2 g/mm2. In a parallel set of experiments recordings were made from single neurons in the caudal trigeminal nucleus of the anaesthetized rat. Neurons were classified according to their responses to a range of thermal and mechanical stimuli applied to the face. Three classes of neuron responded exclusively to mechanical stimuli and four classes responded to thermal stimuli (usually in addition to responding to mechanical stimuli). The mean thermal threshold of neurons responsive to warming stimulation was 44.4 degrees C. Neurons responsive to innocuous warming were located in deeper laminae. Many of the neurons responsive to noxious heat appeared to show an exponential relation between temperature and firing rate. An argument is made for a direct role of exponentially responding neurons in thermal nociception. The distribution of all neuronal response thresholds was left-skewed compared with a normal distribution, whereas the behavioural escape thresholds approximated a normal distribution. PMID- 2215932 TI - Neuropeptide Y co-exists with vasoactive intestinal polypeptide and acetylcholine in parasympathetic cerebrovascular nerves originating in the sphenopalatine, otic, and internal carotid ganglia of the rat. AB - Neuropeptide Y co-exists with noradrenaline in the majority of the sympathetic nerves supplying cerebral blood vessels. However, after sympathectomy in the rat the number of cerebrovascular neuropeptide Y nerve fibers are only reduced in number despite a complete disappearance of the adrenergic markers. The origin of these non-sympathetic neuropeptide Y fibers was studied by nerve transections and retrograde axonal tracing utilizing True Blue. Three days after bilateral superior cervical sympathectomy, the number of neuropeptide Y-containing nerve fibers decreased to about 40% of that in non-treated animals. One week after True Blue application on the proximal portion of the middle cerebral artery, the tracer accumulated in neurons of the sphenopalatine, otic, and internal carotid ganglia. Of these cells 80%, 95% and 5%, respectively, were neuropeptide Y positive. Some of the True Blue/neuropeptide Y-positive cells displayed immunoreactivity for vasoactive intestinal polypeptide and some were positive for choline acetyltransferase. Two weeks after bilateral removal of the sphenopalatine ganglion or transection of postganglionic fibers from the ganglion reaching the pial vessels through the ethmoidal foramen, together with subsequent sympathectomy, no neuropeptide Y-containing nerve fibers could be observed on the anterior cerebral and internal ethmoidal artery or the distal portion of the middle cerebral artery, whereas a few nerve fibers remained on the proximal portion of the middle cerebral artery, internal carotid artery, and the rostral portion of the basilar artery. In conclusion, neuropeptide Y in cerebrovascular nerves is co-stored not only with noradrenaline in sympathetic nerves from the superior cervical ganglion, but also with acetylcholine (reflected in the presence of choline acetyltransferase) and vasoactive intestinal polypeptide in parasympathetic nerves originating in the sphenopalatine, otic, and internal carotid ganglia. PMID- 2215934 TI - Implementation plan for the decade of the brain: executive summary. PMID- 2215935 TI - The transformation of neurologic practice. PMID- 2215936 TI - Pre-trigeminal neuralgia. AB - Eighteen patients who subsequently developed typical trigeminal neuralgia experienced a prodromal pain termed "pre-trigeminal neuralgia." These patients described their prodromal pain as a toothache or sinusitis-like pain lasting up to several hours, sometimes triggered by jaw movements or by drinking hot or cold liquids. Typical trigeminal neuralgia developed a few days to 12 years later, and in all cases affected the same division of the trigeminal nerve. Six additional patients experiencing what appeared to be pre-trigeminal neuralgia became pain free when taking carbamazepine or baclofen. Recognition of pretrigeminal neuralgia makes it possible to relieve the pain with appropriate medications and avoid unnecessary irreversible dental procedures. PMID- 2215937 TI - Hemiplegia in posterior cerebral artery occlusion. AB - We report 4 patients with hemiplegia due to a posterior cerebral artery occlusion. Associated clinical signs were aphasia, alexia or a neglect syndrome, hemianopia, and hemisensory loss. Hemiplegia was due to infarction in the lateral midbrain. The level of the occlusion in the posterior cerebral artery may be located distal to the junction with the posterior communicating artery. PMID- 2215938 TI - Capsular genu syndrome. AB - We report 5 patients with unilateral infarct and 1 with hemorrhage limited to the genu of the internal capsule. The most prominent finding was contralateral facial and lingual hemiparesis with dysarthria. Three patients also showed unilateral mastication-palatal-pharyngeal weakness, and 1 had unilateral vocal cord paresis. Mild limb involvement was limited to hand weakness in 4 patients. Our findings suggest that the majority of motor corticopontine and corticocobulbar fibers are located in the genu of the internal capsule. The faciolingual syndrome and its variants are highly suggestive of capsular genu stroke. PMID- 2215939 TI - Tonic contraversive ocular tilt reaction due to unilateral meso-diencephalic lesion. AB - We studied 4 patients with tonic contraversive ocular tilt reactions due to unilateral, paramedian, mesodiencephalic lesions. This is in contrast to the only 2 previously reported patients with ocular tilt reactions due to unilateral mesodiencephalic lesions, each of whom had a paroxysmal ipsiversive ocular tilt reaction. This new finding is considered in the context of previous clinical and experimental data on the various types of ocular tilt reactions that follow stimulation or destruction of the peripheral and central vestibular system. Otolithic inputs to the interstitial nucleus of Cajal from the contralateral vestibular nucleus and motor outputs from the interstitial nucleus of Cajal to cervical and ocular motoneurons could be involved in the ocular tilt reaction. We propose that in patients with unilateral meso-diencephalic lesions, a tonic contraversive ocular tilt reaction could be due to persistently decreased resting activity of ipsilateral interstitial nucleus neurons, whereas a paroxysmal ipsiversive ocular tilt reaction could be due to transiently increased activity of the same interstitial nucleus neurons. Cases of ocular tilt reaction due to unilateral meso-diencephalic lesion point to the existence of a crossed graviceptive pathway between the vestibular nucleus and the contralateral interstitial nucleus of Cajal. PMID- 2215940 TI - Acute naming deficits following dominant temporal lobectomy: prediction by age at 1st risk for seizures. AB - Age at 1st risk for seizures may predict anomia following dominant anterior temporal lobectomy. We assessed confrontation naming before and 2 to 3 weeks after surgery in 45 right-handed patients grouped by side of focus and presence or absence of early (less than or equal to 5 years) risk factors. After left lobectomy, 6 of 10 (60%) patients with no early risks demonstrated significant decline (greater than or equal to 25%) in naming, but none of the patients with early risks showed this decline. After right lobectomy, there was no change. Cerebral representation of naming may be atypical in patients with early risks. PMID- 2215941 TI - An estimate of the incidence of dementia in idiopathic Parkinson's disease. AB - The proportion of patients with idiopathic Parkinson's disease (PD) who are considered demented ranges from 10% to 15%. Because dementia may affect survival in PD, the incidence rate of dementia, rather than proportion, would be a more accurate measure of disease frequency. We previously estimated the proportion of patients with PD and dementia to be 10.9% from the records of a cohort with the idiopathic form of PD in a major medical center. We reviewed the clinical records of this cohort after 4 years and 9 months to estimate the incidence rate of dementia. We identified 65 new cases of dementia from the 249 patient-records available. Using the number of person-years of follow-up for each case as the denominator, we estimated the overall incidence rate to be 69 per 1,000 person years of observation. The mean age of this cohort was 71.4 years. The cumulative incidence of dementia increased with age. By 85 years of age, over 65% of the surviving members of the cohort were demented. The age-specific incidence rates for dementia in this cohort of PD were significantly greater than for a similarly aged cohort of healthy elderly people. The age-specific standard morbidity ratios indicated that, compared with people of similar ages, patients with PD have the highest increase in risk for dementia between ages 65 and 75. PMID- 2215942 TI - Reliability of NINCDS-ADRDA clinical criteria for the diagnosis of Alzheimer's disease. AB - Although the NINCDS-ADRDA Work Group has recently developed uniform clinical criteria for the diagnosis of Alzheimer's disease (AD), inter-rater reliability studies of these criteria are few. We report a study in which 2 neurologists and 2 psychiatrists independently reviewed clinical data abstracted from the records of 30 demented subjects and 10 nondemented control subjects participating in a longitudinal study of AD at the University of Pittsburgh. We recorded the clinical data on a standardized form; the subjects' identity and clinical and pathologic diagnoses were omitted. Each physician diagnosed each case according to the NINCDS-ADRDA criteria. We calculated the inter-rater agreement for all possible 2-way combinations of clinicians with the Kappa statistic, which ranged from 0.36 (fair agreement) to 0.65 (substantial agreement). We conclude that current NINCDS-ADRDA criteria enable moderate levels of agreement among clinicians in general. PMID- 2215943 TI - Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. AB - The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age. PMID- 2215944 TI - Borrelia burgdorferi infection of the brain: characterization of the organism and response to antibiotics and immune sera in the mouse model. AB - To learn more about the neurologic involvement in Lyme disease, we inoculated inbred mice with the causative agent of Lyme disease, Borrelia burgdorferi. We cultured brains and other organs, and measured anti-B burgdorferi antibody titers. We further studied a brain isolate for its plasmid DNA content and its response in vitro to immune sera and antibiotics. One strain of B burgdorferi, N40, was consistently infective for mice, and resulted in chronic infection of the bladder and spleen. SJL mice developed fewer culture-positive organs and had lower antibody titers than Balb/c and C57Bl/6 mice. Organism was cultured from the brain early in the course of infection, and this isolate, named N40Br, was further studied in vitro. The plasmid content of N40Br was different from that of the infecting strain, implying either a highly selective process during infection or DNA rearrangement in the organism in vivo. N40Br was very sensitive to antibiotics, but only after prolonged incubation. Immune sera from both mice and humans infected with B burgdorferi were unable to completely kill the organism by complement-mediated cytotoxicity. These data demonstrate that B burgdorferi infects the brain of experimental animals, and is resistant to immune sera in vitro but sensitive to prolonged treatment with antibiotics. PMID- 2215945 TI - Chinese-white differences in the distribution of occlusive cerebrovascular disease. AB - The distribution of cerebrovascular lesions is affected by race. Blacks and Japanese have more intracranial occlusive cerebrovascular disease, while whites have more extracranial disease. Despite a high incidence of stroke in China, there are few formal studies of the distribution of vascular occlusive disease in Chinese populations. We compared clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease. In symptomatic vascular territories, whites had more severe (greater than or equal to 50% stenosis) extracranial lesions, while Chinese had more severe intracranial lesions. When we counted mild and severe lesions in a symptomatic territory, whites had more extracranial lesions while Chinese had more intracranial lesions. When we combined symptomatic and asymptomatic territories, whites had more extracranial lesions, while Chinese had more intracranial lesions. White patients reported more transient ischemic attacks. The distribution of lesions, however, was not explained by differences in incidence of transient ischemia, hypertension, diabetes, hypercholesterolemia, or ischemic heart disease between the groups. The preponderance of intracranial vascular lesions in Chinese patients is similar to that seen in blacks and Japanese. Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations. PMID- 2215946 TI - Multiple sclerosis sibling pairs: clustered onset and familial predisposition. AB - We evaluated 48 relapsing-remitting multiple sclerosis (R/R MS) sibling pairs derived from 44 families for age and date of onset of MS symptoms, clinical course, and family history of MS. Age- and sex-matched R/R MS clinic patients provided a statistical comparison group. The age of onset tended to cluster within multiplex families. The initial symptom of MS occurred within 5 years of age in 30/48 sibling pairs compared with 16/48 controls. A positive family history of MS (other than siblings) was present in 43% of the multiplex families compared with 20% among simplex controls. In 1st-, 2nd-, and 3rd-degree relatives who had lived into the age at risk, 22/1,134 family members of multiplex sibling pairs had probable or definite MS compared with 10/1,215 control family members. Age of onset clustering in siblings concordant for R/R MS and an increased risk of MS in other family members suggest that factors influencing disease onset may be in part inherited in these kindreds. PMID- 2215947 TI - Abnormal pulsatile secretion of luteinizing hormone in men with epilepsy: relationship to laterality and nature of paroxysmal discharges. AB - We compared the pulsatile secretion of luteinizing hormone (LH) between 13 men with clinically and electrographically documented temporal lobe seizures and 8 age-matched controls. Serum for LH measurement was drawn every 15 minutes during 8 hours of EEG telemetry in both groups. The 2 groups did not differ significantly in average mean baseline LH secretion, total LH secretion, or average pulse amplitude. The group with seizures, however, showed a significantly greater (p less than 0.05) variability of baseline LH secretion and pulse frequency. Among the men with unilateral paroxysmal EEG findings, pulse frequency was significantly greater (p = 0.05) with right epileptiform discharges or left slowing (6.4 +/- 0.4) than with left epileptiform discharges or right slowing (3.0 +/- 1.3). The relationship of pulse frequency to the nature and laterality of paroxysmal discharges makes it unlikely that endocrine abnormalities can be attributed to medication alone and strengthens the notion that temporal lobe epileptiform discharges may disrupt hypothalamic regulation of pituitary secretion. PMID- 2215948 TI - Cortical tremor: a variant of cortical reflex myoclonus. AB - Two patients with action tremor that was thought to originate in the cerebral cortex showed fine shivering-like finger twitching provoked mainly by action and posture. Surface EMG showed relatively rhythmic discharge at a rate of about 9 Hz, which resembled essential tremor. However, electrophysiologic studies revealed giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex and premovement cortical spike by the jerk-locked averaging method. Treatment with beta-blocker showed no effect, but anticonvulsants such as clonazepam, valproate, and primidone were effective to suppress the tremor and the amplitude of SEPs. We call this involuntary movement "cortical tremor," which is in fact a variant of cortical reflex myoclonus. PMID- 2215949 TI - Topographic mapping of electrophysiologic measures in patients with homonymous hemianopia. AB - We analyzed electroencephalographic (EEG) activity and spatial distribution of the pattern-reversal visual evoked potential (PVEP) in 20 patients with unilateral lesions in the retrochiasmal visual pathways. Focal abnormalities that were consistent with lesion location were present in the topographically analyzed EEG or VEP of 85% of the patients, compared with a 70% detection rate for conventional analysis techniques. Quantitative analysis of spectrally analyzed EEG revealed focal abnormality in 7 patients whose conventional EEG was interpreted as either normal or diffusely slow. However, focal paroxysmal spikes present in the EEG of 1 patient were missed by EEG mapping, and a false localization of quantitative EEG abnormality contralateral to the lesion occurred in 1 patient. Topographic analysis of the PVEP was no more sensitive to retrochiasmatic lesions than conventional analysis of 2 lateral occipital electrodes. We conclude that topographic mapping is a valid technique in the detection of localized cerebral lesions. PMID- 2215950 TI - Dystonia in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. AB - Adult-onset dystonia-parkinsonism is a syndrome in search of a pathology. We therefore reviewed the literature on dystonic manifestations in autopsy-proven cases of multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and idiopathic Parkinson's disease (PD). Only 6 of 140 autopsy reports of MSA remarked on the presence of dystonia in life, but personal observations suggest prominent antecollis may develop at some stage in up to 1/2 of sufferers. Similarly, very few (15/118) clinicopathologic observations on PSP included convincing dystonic manifestations, in contrast to some clinical reports where blepharospasm and early limb dystonia were prominent. Virtually any form of focal and segmental dystonia may sometimes occur with clinically diagnosed PD, with occasional descriptions of hemidystonia-hemiparkinsonism. However, there is pathologic confirmation of this diagnosis in only 1 case. With many patients thought clinically to have PD proving pathologically to have another cause for their parkinsonism, the true frequency and the range of dystonic manifestations acceptable in PD remain unknown. PMID- 2215951 TI - Borderzone hemodynamics in cerebrovascular disease. AB - To investigate the possible existence of chronic selective hemodynamic impairment in the arterial borderzone regions of the brain, we used positron emission tomography (PET) to measure regional mean vascular transit time (rt, equal to the ratio of regional cerebral blood volume to cerebral blood flow) and regional oxygen extraction fraction (rOEF) in 32 patients with either severe internal carotid artery stenosis or occlusion and 11 normal controls. Twenty-four of the patients had had TIAs or amaurosis fugax from 1 to 60 days before PET; all had normal brain CT. We used a stereotactic localization method to locate the anterior and posterior borderzone regions of the middle cerebral artery (MCA) territory. We then calculated ratios of each borderzone to the ipsilateral MCA territory for both rt and rOEF. There was no significant difference from control ratios in any patient subgroup including those with greater than or equal to 75% stenosis or occlusion, those with or without contralateral greater than or equal to 50% stenosis, or those with abnormal hemodynamics in the MCA territory. We therefore found no evidence for selective borderzone hemodynamic impairment in this group of patients with severe carotid artery disease. PMID- 2215952 TI - Diffuse CNS involvement in systemic lupus erythematosus: intrathecal synthesis of the 4th component of complement. AB - In extracerebral systemic lupus erythematosus (SLE), the complement system plays a prominent pathogenic role, and decreased serum concentration of the 4th component (C4) is a reliable indicator of systemic disease activity. In diffuse CNS-SLE, however, the pathogenic role of complement is less clear. In 12 patients with active diffuse CNS-SLE presenting with delirium (4), organic personality syndrome (3), or generalized seizures (5), we determined the CSF indexes of the complement components C3, C4, and factor B, and of IgG, IgA, and IgM. There was a significant increase of the C4 index in these patients compared with controls and a significantly higher CSF C4 index in patients with an increased IgM index. We conclude that intrathecal C4 is being produced in diffuse CNS-SLE. PMID- 2215953 TI - Fresnel prisms improve visual perception in stroke patients with homonymous hemianopia or unilateral visual neglect. AB - We randomly assigned 39 patients with stroke and homonymous hemianopia or unilateral visual neglect to treatment with 15-diopter plastic press-on Fresnel prisms (n = 18) or to serve as controls (n = 21). Baseline evaluations of visual perception and activities-of-daily-living (ADL) function were similar for both groups. After 4 weeks, the prism-treated group performed significantly better than controls on the following: (1) Motor Free Visual Perception Test; (2) Line Bisection Task; (3) Line Cancellation Task; (4) Harrington Flocks Visual Field Screener; and (5) Tangent Screen Examination. There was no significant difference in Barthel ADL assessment at 4 weeks. Thus, treatment with 15-diopter Fresnel prisms improves visual perception test scores but not ADL function in stroke patients with homonymous hemianopia or unilateral visual neglect. PMID- 2215955 TI - Gadolinium-MRI in acute transverse myelopathy. AB - A patient with acute transverse myelopathy (ATM) had serial magnetic resonance imaging (MRI) studies before and after administration of gadolinium (Gd-DTPA). Gd DTPA-MRI was useful in estimating the pathologic extent and residual deficit expected in ATM. PMID- 2215954 TI - Comparison of algorithms of testing for use in automated evaluation of sensation. AB - Estimates of vibratory detection threshold may be used to detect, characterize, and follow the course of sensory abnormality in neurologic disease. The approach is especially useful in epidemiologic and controlled clinical trials. We studied which algorithm of testing and finding threshold should be used in automatic systems by comparing among algorithms and stimulus conditions for the index finger of healthy subjects and for the great toe of patients with mild neuropathy. Appearance thresholds obtained by linear ramps increasing at a rate less than 4.15 microns/sec provided accurate and repeatable thresholds compared with thresholds obtained by forced-choice testing. These rates would be acceptable if only sensitive sites were studied, but they were too slow for use in automatic testing of insensitive parts. Appearance thresholds obtained by fast linear rates (4.15 or 16.6 microns/sec) overestimated threshold, especially for sensitive parts. Use of the mean of appearance and disappearance thresholds, with the stimulus increasing exponentially at rates of 0.5 or 1.0 just noticeable difference (JND) units per second, and interspersion of null stimuli, Bekesy with null stimuli, provided accurate, repeatable, and fast estimates of threshold for sensitive parts. Despite the good performance of Bekesy testing, we prefer forced choice for evaluation of the sensation of patients with neuropathy. PMID- 2215956 TI - Right-left disorientation in dementia of the Alzheimer type. AB - We demonstrated that right-left orientation (R/L-O) on a confronting subject is more impaired in patients with dementia of the Alzheimer type than in patients with multi-infarct dementia of comparable degree of dementia. The impairment in R/L-O is independent of aphasia and spatial disorientation. PMID- 2215957 TI - Effect of plasmapheresis on serum and CSF autoantibody levels in CNS paraneoplastic syndromes. AB - We compared the effect of plasmapheresis on antineuronal autoantibody titers in the serum and CSF of 3 patients with CNS paraneoplastic syndromes. Plasmapheresis reduced the serum autoantibody titer to 20% of the initial levels in the 3 patients, but the CSF autoantibody titer decreased only in the patient with severe damage of the blood-brain barrier. PMID- 2215958 TI - Aggravation of human and experimental myasthenia gravis by contrast media. AB - After observing a 72-year-old myasthenic patient develop an acute myasthenic exacerbation following the administration of routine diagnostic IV contrast material, an observation rarely described in the literature, we used the experimental autoimmune myasthenia gravis model in rabbits injected with a contrast agent to simulate the situation. There was significant worsening of the decremental response to 3 Hz repetitive nerve stimulation from 40 +/- 29% to 55 +/- 27% following the IV administration of contrast agent at doses similar to those used in humans. IV calcium partially reversed this aggravation. Caution is merited when myasthenic patients are administered contrast media. PMID- 2215959 TI - Dopamine beta-hydroxylase activity in cerebrospinal fluid of idiopathic torsion dystonia. AB - Since a postmortem biochemical study and a genetic linkage study of idiopathic torsion dystonia suggested possible involvement of dopamine beta-hydroxylase (DBH), we determined CSF DBH activities of Jewish and non-Jewish patients with childhood-onset idiopathic torsion dystonia and found no differences from a control population. PMID- 2215961 TI - Inconsistent response to divalproex sodium in hemichorea/hemiballism. AB - We report 6 patients with hemichorea/hemiballism of vascular origin who were treated with divalproex sodium (Depakote). Four of 6 responded initially. Marked improvement was seen in 2 patients only and in 1 of these hemiballism recurred despite continuing therapy. Divalproex sodium is not uniformly effective in the treatment of hemichorea/hemiballism. PMID- 2215960 TI - L-tryptophan-induced eosinophilia-myalgia syndrome and myopathy. PMID- 2215962 TI - Mononeuropathy multiplex in tryptophan-associated eosinophilia-myalgia syndrome. PMID- 2215963 TI - Coincidence of myoclonus and multiple sclerosis: dramatic response to clonazepam. PMID- 2215964 TI - Isolated complete post-traumatic trigeminal neuropathy. PMID- 2215965 TI - Trigeminal neurotrophic ulceration with Wallenberg's syndrome. PMID- 2215966 TI - The Denny-Brown collection. PMID- 2215967 TI - 'Monocular' versus 'uniocular'. PMID- 2215968 TI - PSP risk factors. PMID- 2215969 TI - Dysphagia in Chiari malformations. PMID- 2215970 TI - Paraneoplastic motor neuron disease. PMID- 2215971 TI - Do environmental toxins cause Parkinson's disease? A critical review. PMID- 2215972 TI - Oxidation reactions in Parkinson's disease. AB - Free radicals generated from oxidation reactions may contribute to the pathogenesis of Parkinson's disease (PD). Free radicals are capable of reacting almost instantaneously with membrane lipids and causing lipid peroxidation, membrane injury, and cell death. Dopamine is metabolized by oxidation reactions capable of generating free radicals. Recent evidence indicates that the substantia nigra of patients with PD contains increased iron, which enhances oxidation, and decreased glutathione, which protects against the formation of free radicals. Further, the end products of lipid peroxidation are increased in the substantia nigra of patients with PD, supporting the notions that free radicals are being generated and may contribute to dopamine neuronal death. This hypothesis suggests that antioxidant therapies may slow the rate of progression of PD and raises concern that metabolites of levodopa therapy may accelerate the rate of neuronal degeneration. PMID- 2215973 TI - Levodopa therapy in Parkinson's disease. PMID- 2215974 TI - The genetics of Parkinson's disease: a reconsideration. PMID- 2215975 TI - Predicting Parkinson's disease. PMID- 2215976 TI - [ARDS in MOFS (multiple organ failure syndrome). How to direct the therapy? A case report of MOFS in AIDS]. AB - A young AIDS patient was admitted to the Intensive Therapy ward of our hospital with ARDS. The case raised the question of how medical and nursing personnel should face the problem of "suitable treatment for a terminally ill patient". Therapy was based on invasive methods such as mechanical ventilation and the insertion of catheters to monitor vital parameters. The evolution of ARDS in MOFS revealed the difficulty of sustaining vital parameters and avoiding pluriorganic damage. PMID- 2215977 TI - [Loco-regional anesthesia in minor surgery of the breast]. AB - Breast minor surgical operations, either demolitive or reconstructive, are more frequently effected by day-hospital modalities, to obviate to room scarcity and to meet patients requirements. Several patients, due to age or to concomitant pathologies, show risks caused by premature dismissal after having general anaesthesia. This problem led Authors to find an alternative loco-regional anaesthesia. Good results encouraged them to extend this method. PMID- 2215978 TI - [Effectiveness of topical selective decontamination, without systemic antibiotic prophylaxis, in prevention of pulmonary infection in intensive care]. AB - Forty-seven patients admitted in our general ICU and treated with Selective Digestive Decontamination (SDD) without any systemic antibiotic prophylaxis, were prospectively studied and compared with an historical group of 50 non treated subjects. The 2 groups were no different as to underlying disease, age, sex and prognostic index (SAPS). In the treated group was recorded an important and statistically significant reduction in the incidence of pneumonia and in the frequency of pulmonary infections caused by enterobacteriaceae and pseudomonceae. Gram-positive identification in tracheal aspirates was not significantly different in the two groups as well as the incidence of "early pneumonia". In the treated group, a sharp decrease of the total amount of fever-days through ICU stay was observed. The antibiotic consumption resulted to be an overall 28.3% lower in the group treated with, SDD with particular regard to broad-spectrum ones. PMID- 2215979 TI - [Cerebral perfusion pressure in endocranial hypertension in comatose head-injured patients]. AB - The aim of the intensive care of the injured is the coupling of the availability and the requirement of the cerebral metabolic substates. The measurement of the cerebral blood flow is not currently available at the bedside and less direct monitoring is required. The cerebral perfusion can be estimated looking at the cerebral perfusion pressure (CPP), that can be easily measured using intracranial pressure (ICP) and the systemic arterial pressure (MAP) monitoring. Hundred twenty-one consecutive head injured admitted to an Intensive Care Unit were studied assessing the severity of the neurological injury, the CT-Scan diagnosis of the intracranial lesion, the Trauma Score and the behavior of the ICP and MAP. The outcome was classified according to a modified version of the Glasgow Outcome Scale. More than 77% of the patients suffered raised intracranial pressure above 20 mmHg and 16 of them had a CPP less than 60 mmHg for more than 5 minutes. The outcome was directly related to the degree of intracranial hypertension and to the severity of insufficient CPP. The treatment of the severe head injured must be aimed at maintaining a good CPP, because of the close relationships between this value and the prognostic result. The monitoring of the ICP is a reliable and relatively safe procedure in this series, where the rate of infections complicating the intracranial recording is less than 3%. PMID- 2215980 TI - [Propofol and tetanus]. PMID- 2215981 TI - [Strychnine poisoning. A clinical case]. AB - A patient was admitted following ingestion of 300 mg of strychnine. Early diagnosis and timely reanimation treatment led to his full recovery though he had swallowed a quantity of strychnine greater than the medium lethal dose (50-100 mg for adult). PMID- 2215982 TI - [Acute tubular necrosis after renal transplantation. Multifactoral analysis]. AB - Acute Tubular Necrosis (ATN) is a relatively common complication occurring after cadaver kidney transplant. In 64 human renal grafts performed in our center the influence of some factors on the incidence of ATN, related to donor and recipient, was evaluated. The total incidence of ATN was 26.5%. As far as factors related to donor are concerned, the donor's provenance (our medical center versus other centers) resulted statistically significant (p less than 0.01). The incidence of ATN was 17% when the donor came from our intensive care unit, compared with 52% of incidence observed when donor came from other medical centers. As far as factors related to recipients are concerned, the mean and systolic arterial pressure (both measured at the time of unclamping the renal vessels) resulted statistically significant (p less than 0.01 and 0.05 respectively). The influence of mean arterial pressure on the incidence of ATN suggests the administration of inotropic and vasopressant drugs in selected patients before and after organ reperfusion in order to maintain an adequate renal perfusion. PMID- 2215983 TI - [Microbiologic flora in two different periods in intensive care units]. AB - Bacterial examinations performed in two periods (Nov. 1985-Feb. 1986) and Nov. 1988-Feb. 1989) on materials taken from patients admitted into two similar Intensive Care Units (ICU) of the same hospital were evaluated. Excluding oropharyngeal swab cultures, which were performed only in the second period, Gram positive bacteria were 45.3% in 1985-1986 and 62.3% in 1988-1989 and Gram negative fell from 41.9% to 29%. The percentage of fungi remained unchanged. Microorganisms did not grow in 33.3% of tracheal aspirate specimens in 1985-1986 and in 54.3% in 1988-1989, probably depending on the larger number of patients with decompensated chronic respiratory failure treated in the second period. Usually the microorganisms found in the trachea was also in the oropharynx; Gram negative were only 5.1% of the microorganism collected in the oropharinx. The authors emphasize the increase of Gram positive bacteria in ICUs and suggest that the low rate of pneumonia observed in this study depends mostly on the good neurologic state of their patients. PMID- 2215984 TI - [Peridural anesthesia and narcosis with propofol in thoracic surgery]. AB - Twelve patients undergoing elective thoracic surgery because of lung cancer, have been studied. The anesthetic management included: continuous epidural anesthesia with bupivacaine (T6-T7), continuous infusion of propofol and vecuronium, mechanical ventilation with an oxygen/air mixture. We evaluated the perioperative analgesia and the cardiovascular side effects of two groups of patients differing for the position (supine or lateral) selected to administer the local anesthetic. We also analysed the most important characteristics of the recovery from anesthesia (degree of analgesia and consciousness, respiratory function and cooperation with physiotherapeutic manoeuvres). The authors conclude that, although the number of patients studied is limited, there are no significant differences between the two groups for intraoperative analgesia and hemodynamic imbalance; the anesthetic technique employed is a reliable alternative to classic balanced anesthesia, because seems to reply very well to the mayor purposes of thoracic surgery. Moreover it makes the operative room free from pollution caused by volatile anesthetics. PMID- 2215985 TI - [Propofol-ketamine vs propofol-fentanyl in short gynecologic surgery]. AB - The study was performed to investigate efficacy and tolerability of the association propofol-ketamine as alternative to propofol-fentanyl. Forty female, classified ASA I-II, aged 18-50 years and scheduled for short gynecologic procedures under general anesthesia were included in a comparative, randomized, single blind study. Patients were divided in two groups; in group K anesthesia was induced with propofol 1.5 mg/kg and ketamine 1 mg/kg i.v. In group F anesthesia was induced with propofol 2.5 mg/kg and fentanyl 1.5 micrograms/kg. Arterial blood pressure (BP), heart rate (HR), respiratory rate (RR) and arterial O2 saturation (SATO2) were measured. Though preliminary, our data suggest that the association propofol-ketamine reach an adequate level of anesthesia with few and negligible effects on cardiorespiratory system, thus allowing a better operability and safety. The incidence of post operative psychotic disturbances seems to be low and moderate. We can't draw any definitive conclusion, but we think that other studies should be performed to clarify the possible role of ketamine in propofol anesthesia. PMID- 2215986 TI - [Atracurium with halothane and isoflurane in pediatric anesthesia]. AB - The study was carried out to assess the effects of atracurium neuromuscular blockade in children anaesthetized with N2O:O2: halothane vs N2O:O2: isoflurane. Thirty-two ASA I-II children, age 1-13 yr, undergoing elective surgery, were divided into two groups according to age and the mode of anaesthesia induction. Anaesthesia was induced in the younger children (group 1: 1-6 yr) with nitrous oxide and inspired halothane or isoflurane in oxygen via a face mask. Intravenous thiopental (6-7 mg/kg-1) was used to induce anaesthesia in older children (group 2: 7-13 yr). Each group of patients was randomly allocated to two groups each receiving halothane (group A: n = 8) or isoflurane (group I: n = 8). Halothane 0.8% end-tidal and isoflurane 1% end-tidal as anaesthesia maintenance. A bolus dose of atracurium 0.35 mg/kg-1 was administered. Premedication consisted of oral flunitrazepam (0.04 mg/kg-1) and bellafoline (0.02 mg/kg-1). Heart rate (by electrocardiography), arterial pressure (by auscultation) were monitored. Then end-expired carbon dioxide concentration was maintained at 30-40 mmHg. Neuromuscular transmission was evaluated by response to indirect stimulation (TOF) of the ulnar nerve at the wrist via surface electrodes. Conditions for endotracheal intubation were excellent in 25 of the children, good in 6 and poor in 1. The intubation was carried out within 112 s (group 1A), 130 s (group 1 I), 112 s (group 2A) and 135 s (group 2 I) following the administration of atracurium. The maximum twitch depression was recorded in the isoflurane groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2215988 TI - [Anesthesiologic problems in transluminal balloon dilatation of esophageal stenosis in children]. AB - The authors report their anesthesiological experience in 88 cases of transluminal balloon dilatation of esophageal strictures in children. The most serious problems are caused by the need to repeat the dilatation process (up to a maximum of 24 times in one patient) and to the risk of extrinsic mechanical compression of the trachea with consequent transient anoxia. Good sedation was achieved using premedication with haloperidol and diazepam, but was not sufficient to avoid the child's anxiety on entering the operating theatre. Anesthesia using ketamine plus fentanyl, combined with tracheal intubation gave good results in almost all cases, but marked bradycardia was observed in several patients during balloon dilatation. In conclusion, although the technique itself is simple to perform, very careful anesthesia is required to avoid the risk of serious intraoperative complications. PMID- 2215987 TI - [Propofol for the induction and maintenance of anesthesia in ophthalmic surgery]. AB - After brief mention of the chemical and pharmacodynamic properties of diisopropylphenol, personal experience on the administration of propofol for induction and maintenance of anaesthesia for ophthalmic surgery is reported. The results have shown that induction of anaesthesia by propofol injection is associated with a significant and useful reduction of IOP more than TPS induction. Continuous infusion of Diprivan provides satisfactory conditions for intraocular surgery and could be a real choice to thiopentone combined with enflurane. PMID- 2215989 TI - [Paravertebral block of the lumbar plexus. Variations of the original technic]. AB - After studying a hundred or so abdominal CT scans carried out at L5 level and having verified that the interfascial compartment between the quadrate muscle of the lumbi and the psoas muscle is relatively fixed (1.8-2.3 cm), it is proposed to utilise this datum (introduction of the 2 cm) needle after contact with the transverse apophysis of L5) to identify the psoas compartment which contains most of the nerves making up the lumbar plexus. Study of the series and results obtained confirm the value and simplicity of the proposed technique. PMID- 2215990 TI - [Impairment of diuresis in surgical intervention. Role of urinary prostaglandins]. AB - In 8 patients who underwent abdominal surgery for non-neoplastic reasons, we have evaluated some parameters of renal function (PRP, NaU, GFR and diuresis) plasma levels of PRA and ADH and urinary prostaglandins PGE2 and 6-keto-PGF1 alpha. In 4 patients we found that surgery per se was associated with enhancements of PRA, ADH and 6-keto-PGF1 alpha. In other 4 patients, Indomethacin, a specific inhibitor of prostaglandin synthesis was given and this was followed by impairment of natriuresis and RPF. These data confirm the central role of prostaglandins in the control of diuresis and natriuresis and suggest that use of drugs affecting prostaglandin synthesis should be avoided in patients who are undergoing surgery. PMID- 2215991 TI - [Axillary block of the brachial plexus and peripheral paresthesia: a technique to refuse at the outset? Clinical experience]. AB - The axillary brachial plexus blockade by means of stimulating paresthesia and single local anesthetic injection was examined during one year long routine activity in a plastic surgery division. Two-hundred-five blocks were performed evaluating the success percentage, the execution mean time, a sedation utility and the sequelae incidence. The technique was confirmed usefull, easy to perform, well tolerated from the patients. The technique validity, versus the suspiciousness considered by several Authors, is confirmed. PMID- 2215992 TI - [Supraclavicular block of the brachial plexus]. PMID- 2215993 TI - [Comparison of a combination of fentanyl and alfentanil with propofol in brief surgery]. AB - We studied 96 patients undergoing short gynecological procedures. Anaesthesia has been induced with fentanyl 1.5 micrograms/kg (45 patients) or alfentanil micrograms /kg (51 patients) and a hypnotic dose of propofol, and maintained with 70% N2O via facial mask. We observed a better and more rapid control of surgical analgesia with alfentanil, and an earlier recovery of postoperative psychophysical functions. Post-induction apnea has been more frequent and prolonged in the alfentanil group, but no difference in the time necessary to recover an adequate ventilation has been observed between the two groups. Alfentanil anaesthesia determined a more marked intraoperative bradycardia. By virtue of the speed of onset and the short duration of action, alfentanil is a suitable anaesthetic agent for short surgical procedures, particularly in day stay patients. PMID- 2215994 TI - [Electroencephalographic changes during anesthesia with low-dose propofol]. AB - The electroencephalographic changes of 12 patients submitted to anaesthesia with low dosages of propofol (4-2 mg/kg/h + fentanyl) for peripheral vascular surgery have been studied. The standard induction dose of propofol was 2 mg/kg for all the patients. The EEG recording was carried out during the whole length of anaesthesia and the EEG changes were analysed during induction and maintenance phases. During surgical anaesthesia it was always easy to read EEG and also to detect eventual cerebral suffering. On the basis of our results we can suggest this anesthesiologic technique for surgery (for example: carotid surgery) requiring a continuous monitoring of the cerebral function during intra and postoperative phases. PMID- 2215995 TI - [Clinical evaluation of atracurium besylate in patients at risk: major burns]. AB - Atracurium besylate 0.5 mg/kg-1, an intermediate-duration non-depolarizing neuromuscular relaxant, was administered slowly (over 75 sec) in anesthesia induction of 61 patients with major thermal injury undergoing surgical excision and immediate skin-grafting procedures. Patients' mean +/- SD age was 40 +/- 9, body weight 64 +/- 2, burn size ranging from 20% to 90% of body surface area (BSA), postburn day of surgery 5th and more. Induction of anesthesia was carried out with sodium thiopental 2-5 mg/kg-1 plus fentanyl 2.8 micrograms/kg-1 e.v. and after few minutes atracurium 0.5 mg/kg-1 e.v. Anesthesia was maintained with N2O/O2 (70%/30%), isoflurane and small amounts of fentanyl. The mean arterial pressure and heart rate were recorded at I, II, III, IV, V min post atracurium administration. The endotracheal intubation conditions were assessed by a "IOT score". Results are expressed as mean value +/- standard deviation. The significance of the difference in mean values was analysed by t-test. Little haemodynamic changes occurred; intubating conditions showed a relative hyposensitivity of burn patients to atracurium, more severely burned patients (greater than 50-60%) exhibiting greater resistance. PMID- 2215996 TI - [The activity of the "Hygrobac DAR 352" filter in resuscitation patients]. AB - The Authors clinically evaluated the efficacy of the "Hygrobac DAR 352" filter as an antibacterial barrier in a group of patients during mechanical ventilation. After 24 hours of IPVV, a cultural sample has been taken on both sides of the filter introduced in the breathing circuit (patient's side; ventilator's side). While bacteria has been isolated on "the patient's side" of the filter, they were not present on the surface of the "ventilator's side" of the filter. Therefore, the Authors emphasize that the Hygrobac DAR 352 filter represents a good barrier against the passage of bacteria, as it avoids the contamination of the mechanical ventilator by keeping pathogenic organisms coming from patient's airways inside the filter itself. PMID- 2215997 TI - [Cost evaluation of various protocols of anesthesia]. AB - The costs of various anaesthetic techniques are measured using the method suggested by Bailey. These costs are used as a basis for a discussion of the economies that might be practised in the conduct of anaesthesia. PMID- 2215998 TI - [The preventive minitracheotomy as support in difficult intubations: a proposition. Description of a clinical case]. AB - The authors suggest preventive minitracheotomy as a support technique in difficult endotracheal intubation, and report their experience in a case of surgical operation to remove a bony neoformation of C1 and C2 posterior arcs. Endotracheal intubation, difficult because no part of the glottis could be seen, was made possible by preventive minitracheotomy. In this way sedation, myorelaxation and excellent oxygenation during following manoeuvre that resulted atraumatic, were obtained. The small cannula of minitracheotomy was maintained closed during the operation and open for 24 hours thereafter to prevent obstructive complications. It was then removed. PMID- 2215999 TI - [An unusual cause of obstruction of the anesthesia circuit ]. AB - The authors report an unusual accident, uneventful for the patient, due to the mobilization of a foreign body (a piece of tape) inside the anaesthesia circuit, following Emergency Oxygen administration. The accident dynamics and the safety of anaesthesia equipment are discussed. PMID- 2216001 TI - [New methods of electrophysiologic investigation in the diagnosis of brain death]. AB - In the event of suspected brain death it is vital to arrive at a diagnosis as rapidly as possible and with the least chances of error. The paper examines the potentially and possible value of BAER recordings. Results are in line with those of other published studies which underline the value of this method, in spite of the fact it is limited by the possible presence of numerous factors which might invalidate recordings. PMID- 2216000 TI - [Hemodynamic and respiratory aspects in orthotopic liver transplantation]. AB - Intraoperative hemodynamic and respiratory data from one-year experience of orthotopic liver transplantation with veno-venous bypass (10 cases) were collected. Seven different phases of OLT was submitted to one way analysis of variance. Variability is due to degree and duration of liver disease. Basal conditions include high cardiac output with low SVRI, elevated Qs/Qt. and low oxygen consumption. Anhepatic phase shows a lower cardiac index due to reduction in ventricular performance too. The functioning graft raises body oxygen consumption above baseline. Last phases show diminution of MAP and LVSWI and a normal Qs/Qt. PMID- 2216002 TI - [Auditory evoked potentials of the brain stem in brain injury. Prognostic value]. AB - The study of brain stem auditory way in severe head trauma patients with auditory evoked potentials is very important for giving elements about functional and anatomic situation of analyzed neuronal substratum; ABR will be normal or altered in conformity with the level and/or the gravity of the damage. Authors have examined 20 post-traumatic comatose patients pointing out the existence of a strict relation between auditory brain stem responses and prognosis. Authors, in accordance with the ample literature in existence, agree to point out the auditory brain stem responses such as a very effective instrument for the prognostic valuation of post-traumatic comatose patients. PMID- 2216003 TI - Effect of preoperative risk factors on the outcome after surgery for complicated diverticular disease. AB - The influence of age and severity of peritonitis was studied in 111 (16%) out of a total of 694 patients treated for diverticular disease. These 111 patients had complications of the disease and were operated upon by four different approaches. The outcome after surgery was expressed as 30 days mortality, number of operations and postoperative complications per patient, overall hospital stay and number of permanent colostomies in surviving patients. The overall hospital stay lasted significantly longer for patients older than 70 years compared to the younger patients (64 versus 41 days). The complications per patient increased significantly from 1.0 to 1.9 and from 1.1 to 2.7 respectively for an age above 70 years and for peritonitis. Preoperative risk factors as age and peritonitis adequately predict the outcome after surgery for complicated diverticular disease. The type of surgery employed seems more dependent on the perioperative findings than on the superiority of one of the procedures. PMID- 2216005 TI - Acute mesenteric embolism: an appeal for a pro-active diagnostic approach. AB - Acute mesenteric ischaemia can be caused by arterial embolism. The initial aspecific symptoms mostly lead to late recognition of acute mesenteric ischaemia which leads to intestinal infarction. Intestinal infarction with signs of peritonitis has a very high mortality. Since 1982, a pro-active approach is followed in our department. After thorough exclusion of other causes, patients with serious acute abdominal complaints undergo an emergency angiography and/or emergency laparotomy. After confirmation of the diagnosis, primary vascular reconstructive surgery is performed if possible. We have treated eight patients with acute mesenteric embolism according to this policy. Per- and post operatively, three patients died of extensive intestinal infarction. The five surviving patients were on a normal diet and had normal bowel functions at the time of discharge from the hospital. This limited experience shows that a pro active approach in patients with acute mesenteric embolism can result in survival and preservation of a normally functioning alimentary tract. PMID- 2216004 TI - Early complications after surgery for Crohn's disease. AB - A group of 212 patients operated upon for Crohn's disease were studied and the early postoperative complications with related problems were assessed. The morbidity was 28.3 per cent, 60 patients had at least one complication, mainly of septic nature. The mortality was 3.3 per cent (7 patients), sepsis and deep vein thrombosis with pulmonary embolism were the most common causes of death. Postoperative complications were significantly higher (39.7%) (p less than 0.001) in patients with a pre-operative nutritional deficit and in those who had urgent surgery (44.4%) (p less than 0.001). Among patients with pre-operative sepsis, the morbidity was also higher (34.6%), but was not significant. Peri-anastomotic complications (dehiscence, abscess, fistula, bleeding) were apparently more frequent (45.4%) in patients with histological residual Crohn's disease at macroscopically free resection margins although this contrasts with previous series. A proper pre-operative diagnostic approach, adequate peri-operative protein-caloric repletion, antibiotic therapy, prevention of thromboembolism and elective surgery, are still the primary tools in reducing the morbidity and mortality after surgery for Crohn's disease. PMID- 2216006 TI - Haemodynamics and 'optimal' hydration in aortic cross clamping. AB - The effect of optimal hydration on haemodynamics and renal function during infrarenal aortic cross clamping was studied in 26 consecutive patients operated on because of an infrarenal aortic aneurysm. The patients were randomly divided over two groups. The patients of group B (n = 13) were optimally hydrated before the operation. The Starling curve was used as standard. Patients of group A (n = 13) served as control. The pre-operative and postoperative renal functions of both groups were compared, as were the haemodynamic parameters. The haemodynamic parameters were measured at five minutes intervals during the entire procedure. During aortic clamping the heart rate was significantly lower in patients of group B, indicating a lower myocardial oxygen consumption. Neither the haemodynamic parameters nor the renal function showed other beneficial effects on optimal hydration. PMID- 2216007 TI - Left external iliac artery dissection and bilateral renal artery aneurysms secondary to fibromuscular dysplasia: a case report. AB - A case of acute lower limb ischaemia due to spontaneous dissection of the left external iliac artery and coincidental bilateral renal artery aneurysms is reported. Histopathological examination of the resected iliac artery showed features of fibromuscular dysplasia. Dissection of the external iliac artery without involvement of the aorta is extremely rare with only two previously reported cases. The aetiology and management of fibromuscular dysplasia is discussed. PMID- 2216008 TI - Antibiotic prophylaxis in biliary tract surgery--current practice in The Netherlands. AB - A questionnaire about the current practice of antibiotic prophylaxis in biliary tract surgery was sent to the chairmen of the departments of surgery of 175 hospitals in The Netherlands. The Dutch hospitals are classified into three categories depending on the type of residency in general surgery. Overall, 80 per cent replied. Antibiotic prophylaxis in elective cholecystectomy is given in 76 per cent of the clinics (100/132), and single-dose prophylaxis is employed in 28 per cent of the clinics (28/100). In patients with acute cholecystitis, emergency surgery is the treatment of choice in 108 hospitals (82%). Differences in antibiotic prophylaxis between the three categories of hospitals include the omission of prophylaxis in elective cholecystectomy in 31 per cent of the C clinics (vs. 10% in A-clinics and 16% in B-clinics), and the use of single-dose prophylaxis in 13 per cent of the B-clinics (vs. 30% of the A-clinics and 31% of the C-clinics). Since prophylaxis for more than 24 hours has no additional effect and peri-operative prophylaxis in acute cholecystitis is mandatory, antibiotic prophylaxis in biliary tract surgery is inappropriate in at least 31 hospitals in The Netherlands (23%). PMID- 2216009 TI - Developmental shifts in Oedipal behaviors related to family role understanding. PMID- 2216010 TI - The Bears' Picnic: children's representations of themselves and their families. AB - The Bears' Picnic, a new test of preschoolers' representations of self and family, was given to four-year-olds who had been observed with their mothers at twenty months of age. Observed maternal sensitivity and the affective quality of both partners were related to the child's later valuing versus devaluing of self and others. PMID- 2216011 TI - Dialogues with children about their families. PMID- 2216012 TI - Five-year-olds' representations of separation from parents: responses from the perspective of self and other. PMID- 2216013 TI - Family relationships as represented in a story-completion task at thirty-seven and fifty-four months of age. PMID- 2216014 TI - [Doppler flowmetry in temporal arteritis. Indications and limitations]. AB - Doppler test in temporal arthritis. Prescriptions and limits The paper describes the Authors' personal experience in using the Doppler test for the diagnosis of temporal arthritis in a small group of patients clinically suspected of the pathology. The method has proved useful in the diagnosis and follow-up of the disease, but the diagnosis is confirmed by a biopsy of the temporal artery which still plays an important role. PMID- 2216015 TI - [Changes in lymphocyte subpopulations induced by the administration of thymopentin]. AB - Modifications of the levels of T-helper (T4) and T-suppressor (T8) lymphocytes were assessed, together with their ratio, in 17 subjects who had received thymopentine as an adjuvant to Hevac-B vaccination. Two months after treatment with the immunomodulating drug, T4 lymphocytes were considerably increased whereas absolute levels of T8 lymphocytes were decreased in the majority of patients: this led to a net increase in the T4/T8 ratio. This finding leads to the conclusion that all subjects produced anti-HBs antibodies as a means of protection. PMID- 2216017 TI - [Arthromyopathy caused by barbiturates. Description of a clinical case]. AB - The study describes a rare case of arthromyopathy from phenobarbital which affected the right hand of a patient. The case is particularly interesting since symptoms developed after the drug had been taken for only one month. PMID- 2216016 TI - [Endocarditis on prosthetic valve caused by a diphtheroid insensitive to vancomycin]. PMID- 2216018 TI - [External fixators in the treatment of fractures and fractures/luxations of the pelvis]. AB - Combined fractures of the two pelvic arches and severe disjunction of the pubic symphysis are acute lesions which are difficult to treat; in order to avoid poor functional results, the use of external fixatives have now become a routine orthopedic surgical practice. Two cases are reported to illustrate the large numbers of patients treated by the Orthopedic and Traumatological Division of the Ospedale Civile in Alessandria. PMID- 2216019 TI - [Review of 64 cases of hallux valgus surgically treated with the Keller-Leviere technique]. AB - Sixty four cases of hallux valgus treated using the Keller-Lelievre technique during the period from January 1982 to December 1987 are examined. The results achieved reveal the validity and limits of this surgical technique. Having established the prescriptions of the technique, it still represents the simplest and safest method for treating this affection in adult/old-aged patients. PMID- 2216020 TI - [Our experience in the use of Thompson's endoprosthesis in medial fractures of the femur neck]. AB - The study reports the results of a study of a random sample of 40 patients with medial fractures of the collum femoris in whom the caput femoris was substituted by Thompson's cemented prosthesis, taken from a series of 189 operations performed between 1981 and 1987. In conclusion, Thompson's prosthesis is demonstrated to be still valid in patients over 75 years old. PMID- 2216021 TI - [A case of a fracture of the clavicle associated with an acromio-clavicular luxation]. AB - The study reports a rate case of a girl with associated clavicular fracture and acromioclavicular dislocation following a care accident. The pathogenetic mechanism may be attributed to a trauma on the medial shoulder stump which having fractured the clavicle then provoked the acromioclavicular dislocation by continued pressure on that point. It is important to observe that the patient fully recovered, virtually without therapy. PMID- 2216022 TI - [A case of paralytic syndrome of the upper limb caused by tourniquet]. AB - A case of paralytic syndrome of an upper limb in a healthy young man following the application of a tourniquet, accidentally inflated to a pressure of more than 200 mmHg during an operation, is described in which motility was fully recovered after 3 months. The importance of checking equipment periodically is stressed. PMID- 2216023 TI - [Electric shock treatment of poisoning caused by animal venoms]. AB - Poisoning through sting or bite by venomous animals constitutes a medical emergency which is potentially fatal and not easy to resolve. In this work the Authors describe the electric shock treatment (EST) to cure poisoning by animal venoms; such method has now been used for some years for this purpose in different parts of the world (Guderian et al., 1986). The Authors describe the suitability, the effectiveness of the method, the source and the type of electric current to apply; they give usage instructions and probable theory on its working mechanism: although the latter requires a more detailed and rigorous study. They wish for the usage of EST for this purpose to spread in Italy too, although fatal poisoning is rare here, and are devising a portable instrument with the right requirements. PMID- 2216024 TI - [Scorpion sting (Euscorpius, sp.) in Italy and review of scorpionism]. AB - Although they are very common arachnids, the scorpions (Euscorpius, sp.) do not constitute a sanitary problem in Italy, given that their sting determines only local effects. Scorpionism can anyway verify itself following sting exemplaries in Italy with imported gaods or caused by Buthus occitanus, that lives in the south of France. In this review the Authors treat briefly the biology and the toxicology of scorpions, describing the clinical picture of Scorpionism and the relative therapy. PMID- 2216025 TI - [Review of latrodectism and Malmignatta sting (Latrodectus tredecimguttatus) in Italy]. AB - The latrodectism is a rare poisoning rather unknown in Italy and some times fatal. The Authors in this latrodectism review intend to provide information about the Malmignatta spider Latrodectus tredecimguttatus: biology, Italian distribution and peculiarity of its venom. Here are reported the clinical picture of the toxic syndrome, with first principles of differential diagnosis. Afterwards, they face the treatment, illustrating the cases where they can use the antivenom, calcium gluconate or methocarbamol, with modalities, doses and administration stages. PMID- 2216026 TI - [List of abuse substances most requested by drug addicts, particularly in reference to the Alexandria province. Notes for the general practitioner]. AB - The drugs in Italy most requested by addicts, who use them in their constant search for perceptive distortion are listed. The list refers principally to the figures collected in the province of Alessandria. The list is aimed at the general practitioner who usually receives the highest number of requests for prescriptions for such drugs. It is recommended how to behave so as to avoid errors punishable by law. PMID- 2216027 TI - [Assessment of rehabilitation in psychiatry. A study of 50 patients]. AB - Following an analysis of the concept of rehabilitation in psychiatry, the results of the use of the "Disability Assessment Schedule II" in a group of 50 patients (24 males and 26 females), suffering from schizophrenic psychoses, are reported. The opportuneness of a rehabilitation intervention stressed, wherever medium severe disability levels are observed, in order to impede the affective and social destitution characteristic of chronic mental disease. PMID- 2216028 TI - [Preliminary experience in health education in a group of 52 diabetic patients]. AB - The results of a study carried out in a random sample of patients who had filled out a questionnaire of selected questions are reported. The questionnaire was re presented after a cycle of health education and the replies compared so as to assess specific learning. PMID- 2216029 TI - [Hypoglycemia caused by partial deficiency of growth hormone. Description of a clinical case]. AB - A clinical case of a female patient suffering from recurrent, especially nighttime, attacks of hypoglycaemia is reported. Clinical tests found these to be the consequence of partial hypophyseal deficiency of growth hormone. PMID- 2216030 TI - [Normal echography of the liver and the bile ducts]. AB - On account of its high diagnostic precision, widespread availability, its use for the periodic monitoring of patients and its low cost, ectomography now occupies a leading position among the new diagnostic imaging techniques. The present study illustrates the ecostructure, seat, shape, size and relations between the liver and the bile ducts using ultrasonic analysis. PMID- 2216031 TI - [Changes in feeding behavior in anorexic individuals. Description of 2 clinical cases]. AB - The change in the eating behaviour of anorexic individuals has been studied with particular attention to the case of two biovular heterozygotic twins. It is observed that dietetic treatment backed by careful psychiatric therapy is a decisive factor in the resolution of the pathology. PMID- 2216032 TI - [Long-term outcome of severe cranial injury]. AB - Clinical data relating to the admission into hospital of patients who survived severe cranial traumas are reported and are compared with the long-term outcome in order to identify eventual significant prognostic parameters. No particular significant correlations were observed between the parameters in question, but, in accordance with other studies, a close correlation was observed between the duration of the state of coma and the incidence and severity of invalidating effects. PMID- 2216033 TI - [Intravenous anesthesia using propofol in surgical interventions in day hospital routines]. AB - Having illustrated the importance of extending surgical treatment into day hospital situations, the paper underlines the need for anesthetics with short term effects. Two groups of 30 patients were included in the study and underwent anesthesia in day hospital using Propofol or Tiopentone-Enflurane. The results reveal comparable respiratory and hemodynamic effects for the two techniques, but Propofol is more reliable in terms of the lesser side-effects caused and above all the speed of the patient's psycho-physical recovery. PMID- 2216034 TI - [Hyperbaric oxygen therapy in acute carbon monoxide poisoning. Illustration of a treatment protocol]. AB - After a brief digression on the etiopathogenesis of carbon monoxide poisoning, the paper underlines the importance of the timely use of hyperbaric oxygen treatment not only to impede the immediate effects of CO, but also to reduce the incidence of neurological complications. The paper illustrates the paroxysm protocol and hyperbaric oxygen treatment protocol used by the Authors. PMID- 2216035 TI - [Mediterranean boutonneuse fever. Analysis of 48 cases in the Alexandrian community]. PMID- 2216036 TI - [Indigenous dirofilariasis in Alexandria]. PMID- 2216037 TI - [Hymenolepis diminuta: a rare helminthiasis in humans. Description of a clinical case]. AB - The paper describes a case of hymenolepis diminuta, a relatively uncommon helminthiasis in man. The patient examined displayed very particular aspects with regard to the course of the disease and its diagnosis. PMID- 2216038 TI - [Meningitis caused by Streptococcus morbillorum]. AB - A rare case of meningitis from Streptococcus morbillorum is described in a middle aged man. A complete cure was achieved using a combination therapy of Ampicillin and Chloramphenicol. PMID- 2216039 TI - [A case of leiomyoblastoma of the stomach]. AB - Following a brief analysis of the literature, a case of leiomyoblastoma of the stomach is described. The rarity of this form is stressed and the importance of an endoscopic examination for diagnostic purposes and to select the appropriate surgical treatment is underlined. PMID- 2216040 TI - [A rare skin tumor: Merkel cell carcinoma]. AB - A rare case of skin tumour, Merkel cell carcinoma, is reported. The histopathological and clinical features and surgical treatment are reported. PMID- 2216041 TI - [HIV-associated myelodysplasia. Etiopathogenesis, clinical aspects and therapy]. PMID- 2216042 TI - [Refractory anemia with excess of blasts in a HIV-positive patient]. PMID- 2216043 TI - [Common variable agammaglobulinemia. Description of a clinical case]. AB - Common variable agammaglobulinemia is characterized by a decrease in the levels of circulating immunoglobulins, a damaged antibody response to several antigens and an increased susceptibility to infection. A rare case of common variable hypogammaglobulinemia in a young woman who was brought to the authors' attention since she was suffering from meningitis is described. PMID- 2216044 TI - [Intestinal amebiasis in AIDS]. PMID- 2216045 TI - [Type I diabetes mellitus and autoimmunity. Description of 9 clinical cases]. AB - Diabetes mellitus type I can ben divided into two forms, IA and IB, with partially different clinical and pathogenetic characteristics. The present paper looks at type I diabetic patients presenting associated pathologies of autoimmune type, largely involving the endocrine system. PMID- 2216046 TI - [Blastocystis hominis infection in AIDS and correlated pathologies]. AB - Blastocystis hominis may sometimes be found in feces in sufficient quantities to cause symptoms of diseases such as diarrhea abdominal pain, nausea, tenesmus, fever, itching and slight acidocytosis. Three cases of blastocysosis observed in patients with LAS are reported. PMID- 2216047 TI - [HIV-correlated antigens and antibodies in patients treated with zidovudine]. AB - HIV-antigen is an important marker of the evolution of HIV infection and of the response to zidovudine therapy. The study aims to assess the course of HIV correlated antigens and antibodies in 4 patients affected by AIDS or ARC treated with this drug. PMID- 2216048 TI - [Nimesulide in the treatment of postoperative pain in minor orthopedic surgery]. AB - The study assesses the effect of Nimesulide in the treatment of post-operative pain in minor orthopedic surgery. Twenty-five patients who had received regional peridural or subarachnoid anesthesia were included in the study. After a variable interval of 60 to 90 minutes, the average level of pain, evaluated using a "pain score", was considerably reduced. This effect lasted for an average of 360 +/- 120 minutes. There were minimum side-effects. PMID- 2216049 TI - The normal microbial flora of the outer ear canal in healthy Norwegian individuals. AB - The microbial flora of the outer ear canal was determined for 77 healthy individuals (M = 44, F = 33). No growth of any microbe was found in 5% of males and 15% of females. Coagulase-negative staphylococci, dominated by Staphylococcus epidermidis, were the commonest microbe group found (83% of persons sampled). Staphylococcus aureus was found in 7% males and no females. Diptheroids were cultured from 32% of the samples. The only Gram-negative rod found was Hafnia alvei in 4% of individuals. No Vibrio spp. or anaerobic Gram-negative organisms were found. A variety of yeasts and moulds were seen, significantly (p = 0.02) more often in males. In a separate experiment, Malassezia furfur was found in 4/9 males and 0/10 females sampled. Various sampling techniques (dry swab, second dry swab, moist swab) that were compared showed broadly similar results. The normal flora of the outer ear canal is predominantly Gram-positive and the use of a dry swab seems to be a satisfactory method for sample-taking from this area. PMID- 2216050 TI - Cultivation of Chlamydia trachomatis. Different methods of treating the specimens. AB - Specimens of Chlamydia trachomatis were treated either by five different detergents, by ultrasound sonication or by four different buffers before cultivation in cycloheximide-treated McCoy cells. The chlamydial yield by cultivation and the variance of the yield were compared to a standard method using 0.2 molar sucrose in phosphate buffered saline (2SP) without application of detergents or sonication. 2SP was superior to the other buffers. None of the detergents increased the chlamydial yield. Sonication at energy-levels above approximately 1200 Ws/ml reduced the chlamydial yield significantly. Sonication just below this threshold doubled the yield. None of the methods reduced the variance of the yield. PMID- 2216051 TI - Close tip-to-tip contacts between dendrites of transient amacrine cells in carp retina. AB - In isolated retinas of the carp (Cyprinus carpio) placed receptor side up in a plastic chamber, a subclass of amacrine cells, generating a fast ON-OFF transient response to spot and annular light stimuli, were intracellularly recorded and injected with a fluorescent dye, Lucifer yellow (LY). After brief fixation of the same preparations in aldehyde solution, the retinas were wholemounted vitreous side up in a tissue chamber. Under a fluorescence microscope, one LY-injected cell and several dye-coupled cells were seen; these cells belonged to type Fnd, having a fusiform soma, narrow dendritic field and bistratified dentrites in the inner plexiform layer (IPL). To reveal the interconnections between dendrites, one of such dye-coupled cells was further injected with LY. Close tip-to-tip contacts were predominantly found between dendrites of neighboring type Fnd cells in sublaminae a and b of the IPL, respectively. PMID- 2216053 TI - A double immunocytochemical and histochemical technique for demonstration of cholinergic neurons and microglial cells in basal forebrain and neostriatum of the rat. AB - Cholinergic neurons, and their relationship to microglial cells, have been examined by light and electron microscopy with an immunocytochemical and histochemical double-staining technique, in medial septum, diagonal band of Broca, nucleus basalis and neostriatum. This technique may be applied to experimental models of anterograde and retrograde degeneration of the cholinergic neurons of the basal forebrain in order to collect further information relative to the aetiology of degenerative diseases such as Alzheimer's disease. PMID- 2216052 TI - Calmitine: a calcium-binding mitochondrial protein specific for fast-twitch muscle fibers. AB - Mitochondrial fractions were isolated from fast-twitch (EDL), slow-twitch (soleus) and heart muscle of normal rat (WKY). Protein separation by electrophoresis and study of calcium-45 binding showed that a specific calcium protein (designated as calmitine) was present in the mitochondria of fast-twitch muscle but practically inexistent in slow-twitch and cardiac muscle. It seems to be related to calcium uptake by an energy-dependent mechanism. PMID- 2216054 TI - Immunocytochemical localization of manganese superoxide dismutase (Mn-SOD) in the hippocampus of the rat. AB - The immunocytochemical distribution of manganese superoxide dismutase (Mn-SOD) was determined in the rat hippocampus. The enzyme was localized in the mitochondria. CA1 pyramidal cells were weakly immunostained, whereas CA3 pyramidal cells were strongly reactive. These differences in the intensity of the Mn-SOD immunostaining reactions may relate to variations in the sensitivity of subfields of the hippocampus to ischemia. PMID- 2216055 TI - MK-801-induced sprouting by CGRP immunoreactive primary afferent fibers in the dorsal spinal cord of the rat. AB - In the present study, rats received daily injections of the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, over 30 consecutive days. The effects of MK 801 on the distribution of calcitonin gene-related peptide (CGRP)-immunoreactive fibers in the dorsal spinal cord of the rat were subsequently examined. In addition to the normal immunostaining pattern in laminae I, II and lateral V, a dense network of CGRP-immunoreactive fibers was observed along the medial border of the dorsal horn and within the dorsal grey commissure. This marked increase in immunoreactivity was virtually eliminated following dorsal rhizotomy. These observations suggest that MK-801 induces intraspinal sprouting by CGRP immunoreactive primary afferent fibers in vivo. PMID- 2216056 TI - A specific 70 kDa protein induced in the epileptogenic cortex of rats elicits bursting activity and inactivation of potassium current in snail neurons. AB - The capability of a specific 70 kDa (P70) protein produced in cobalt-induced epileptogenic cortex of rat cerebrum in promoting epileptic bursting activity was examined in snail neurons, using the voltage clamp method in combination with the pressure injection technique. Injection of P70 into the neurons elicited bursting activity with paroxysmal depolarization shift together with a reduction in the delayed outward current which was suppressed by tetraethylammonium. These changes of membrane properties induced by P70 were dose-dependently inhibited by prior treatment with the anticonvulsant phenytoin. These findings indicate that P70 causes an inactivation of potassium conductance which may generate epileptic bursting activity. PMID- 2216057 TI - Pre- and postganglionic sympathetic activity in white rami of rats. AB - Multifiber sympathetic activity was recorded from the central end of severed 13th thoracic communicating rami in urethane-anesthetized rats before and after ganglionic blockade by chlorisondamine. Ganglionic blockade decreased nerve discharge by 49 +/- 10% (n = 7) indicating that these rami are composed of postganglionic axons (other than gray rami fibers) as well as preganglionic axons. Histological examination of excised T13 rami showed that postganglionic cell bodies are located along the course of these nerves. PMID- 2216058 TI - A-fibers mediate mechanical hyperesthesia and allodynia and C-fibers mediate thermal hyperalgesia in a new model of causalgiform pain disorders in rats. AB - Unilateral tight ligation of about half of the sciatic nerve in rats rapidly produces sympathetically dependent neuropathic pain which lasts many months and resembles causalgia in humans. The sensory abnormalities detected at the plantar side of the hindpaws include: (1) nocifensive responses to repetitive light touch (allodynia); (2) bilateral reduction in withdrawal thresholds to repetitive von Frey hair stimulation (mechanical hyperesthesia); (3) bilateral reduction in withdrawal thresholds to CO2 laser heat pulses; and (4) unilateral increase in response duration to an intense laser heat pulse (thermal hyperalgesia). Using neonatal capsaicin treatment, we determined the type of afferent fiber remaining in the partially injured nerve, which mediates these disorders. Capsaicin, which destroys most C- and some A delta-fibers in peripheral nerves, had no effect on the touch-evoked allodynia and mechanical hyperesthesia that are produced by partial sciatic nerve injury. These disorders were, therefore, mediated by myelinated fibers. In contrast, thermal hyperalgesia failed to develop in capsaicin-treated rats following partial nerve injury. Thus, thermal hyperalgesia produced by partial nerve injury appears to be mediated by heat-nociceptive C fibers. PMID- 2216059 TI - Evidence for involvement of 5-HT2 and 5-HT1C receptors in the behavioral effects of the 5-HT agonist 1-(2,5-dimethoxy-4-iodophenyl aminopropane)-2 (DOI). AB - DOI (1-(2,5-dimethoxy-4-iodophenyl aminopropane)-2) has recently been suggested as a selective 5-HT2 receptor agonist, but its behavioral effects have not been previously reported. In naive rats, DOI induced dose-dependent shaking behavior, the novel behavior 'skin jerks' (paraspinal muscle contractions), and forepaw tapping of the 'serotonin syndrome'. These behaviors had a similar dose-response and time course and were blocked by the 5-HT2/5-HT1C antagonists mianserin, ritanserin, and methysergide. Skin jerks, unlike other behaviors, were not blocked by 1-propranolol or phenoxybenzamine, drugs with little activity at 5 HT2/5-HT1C sites. Differences in the pharmacology and neuroanatomy between skin jerks and shaking behavior suggest that the 5-HT1C receptor may participate in skin jerks and the 5-HT2 receptor in shaking behavior, but drug coaffinities for 5-HT2 and 5-HT1C receptors require further investigation. PMID- 2216061 TI - Diterpenoids. PMID- 2216060 TI - beta-Endorphin acts on the reproductive tract of female rats to suppress sexual receptivity. AB - Sexual receptivity was suppressed in female rats immediately after the male had ejaculated. The inhibition was prevented by intravaginal injection of naloxone (100 micrograms) before testing and intravaginal injection of beta-endorphin (1.0 micrograms) inhibited sexual behavior in female rats in a manner comparable to that of ejaculation by the male. beta-Endorphin was present in ejaculatory plugs collected from the vagina of female rats (8.2 +/- 0.6 pM) and in seminal fluid collected from male rats (7.7 +/- 0.2 pM). The results suggest that beta endorphin in the ejaculate of the male rat can act on the reproductive tract of the female rat to suppress her sexual behavior. PMID- 2216062 TI - The biosynthesis of shikimate metabolites. PMID- 2216063 TI - Recent progress in the chemistry of indole alkaloids and mould metabolites. PMID- 2216064 TI - Beta-phenylethylamines and the isoquinoline alkaloids. PMID- 2216065 TI - Perspectives on academic dishonesty. AB - Academic dishonest behaviors, such as lying, cheating, and plagiarism, are destructive and must be recognized and addressed early in the development of professional nurses. Faculty must be concerned with the relationship between student integrity in the classroom and clinical or professional behaviors. The authors discuss student motivation and attitudes toward unethical practices, faculty responses, and responsibilities when these incidents arise, and strategies for preventing academic dishonesty. PMID- 2216067 TI - The Greek goddesses speak to nurses. AB - The Greek goddess myths are a uniquely creative medium to teach affirming feminine images to nurses learning about the impact of gender in their personal and professional lives. The author briefly reviews the stories of the goddesses and strategies for integrating goddess literature into nursing courses. PMID- 2216066 TI - Promoting critical thinking skills. AB - Educational accountability requires examination and justification of curriculum elements that will promote critical thinking skills. The authors review theoretical components of critical thinking and provides four examples of teaching strategies used to enhance this cognitive skill. PMID- 2216068 TI - Program evaluation. Part 1: Four generations of theory. AB - Program evaluation is necessary for understanding and improving educational programs in nursing, but it is frequently surrounded by a climate of unease and perplexity. This first article in a two-part series reviews and evaluates extant models of program evaluation using Guba and Lincoln's four generations of evaluation as a theoretical framework. The second article (November/December 1990) examines the state-of-the-art of program evaluation in nursing education and proposes implementation of a responsive model of program evaluation in schools of nursing. The series aims to foster more dynamic, efficient program analysis, thereby enhancing the effectiveness of nursing's educational programs. PMID- 2216069 TI - Teaching students for whom English is a second language. AB - Nursing students for whom English is a second language (ESL) are now found in greater numbers in nursing schools. Their presence in nursing contributes to the diversity of the profession, but the language difficulties these students experience may influence academic achievement. Nurse educators can assist ESL students in reaching their career goal by being aware of the special language problems the students can encounter in academic settings and by instituting early and appropriate retention interventions. PMID- 2216070 TI - RN education: beyond the baccalaureate degree. AB - With an emphasis on post-baccalaureate education, the University of Kansas School of Nursing has restructured its program for registered nurse students. The resultant RN-MS track allows completion of both the baccalaureate and master's degrees in nursing in a 2-year time frame. Computer competencies, individualization of instruction, and substitution of classes are integrated into a streamlined curriculum. PMID- 2216071 TI - Retention of minority nursing students on predominantly white campuses. AB - Minority nursing students at predominantly white colleges may experience psychosocial and academic problems that together influence their decision to remain in the academic system. Estimates of attrition rates for minority nursing students range from a low of 15% to a high of 85%. Two theories for the extremely high attrition rates is that retention strategies frequently have a single focus (academics) and that faculty involved with minority students lack a sense of commitment to help these students. The author identifies academic and psychosocial factors that, singularly or in combination, may make academic success an impossible feat for the minority student. Suggested strategies for improving retention at the prenursing and nursing levels are outlined. PMID- 2216072 TI - The continuing case study. AB - A continuing case study highlighting one extended family was used with generic and RN baccalaureate nursing students to integrate basic nursing concepts, nursing theory, and health assessment content in an integrated curriculum. Unlike traditional case studies, the continuing case study allowed people and health states to change over time, providing a new dimension to case analysis. This method facilitated the application of theory to practice situations and helped students to understand the dynamics of family health. PMID- 2216073 TI - Confusion in older adults: assessment and differential diagnosis. AB - Confusion has long been considered a normal consequence of aging. The growing incidence and cost of this untreated symptom has unfairly condemned many elders to live out their lives at a low level of functioning and has placed unnecessary hardships on their families. This article offers a complete protocol to assess and differentiate arrestible and reversible causes of confusion from irreversible presenile dementia. The history is the most important aspect of the examination of the confused elder. Onset of symptoms, corresponding illness, medication use and time of day that the confusion occurs should be included. Objective data include mental-status exams, but only as a screening tool and stepping stone for other exams. Judgment and abstraction are examined by assessing the client's ability to interpret proverbs and plot a sensible course of action. Special cortical function is assessed by asking the client to draw a house, a clock and a person. A functional pattern assessment specific to the confused elder is included. The general assessment centers on ruling out systemic or mechanical problems in the brain. Possible pathological causes with corresponding lab results, symptoms and clinical data are presented. Confusion is a symptom of many different and often unrelated disease entities. Many of these diseases are preventable, curable or arrestible. A diagnosis of irreversible presenile dementia should never be made without thorough evaluation. The health care provider should refer clients suspected of having irreversible presenile dementia to neurological specialists for confirmation of clinical findings. PMID- 2216074 TI - Taking charge in the air. PMID- 2216075 TI - Mr. Tyler's miracle. PMID- 2216077 TI - Anistreplase for acute M.I. PMID- 2216076 TI - Night shift. PMID- 2216078 TI - A case of no consent. PMID- 2216080 TI - Helping nurses be nurses. PMID- 2216079 TI - Myra offered nothing but complaints. PMID- 2216081 TI - Knowing when to look for a new job. PMID- 2216082 TI - Making time work for you. PMID- 2216083 TI - Personal power: your key to success. PMID- 2216084 TI - From A to Z: tips & time-savers for career development. PMID- 2216085 TI - Kate's comeback. PMID- 2216086 TI - Action stat! Alcohol withdrawal syndrome. PMID- 2216087 TI - Understanding the fine line between law and ethics. PMID- 2216088 TI - Soldier boy. PMID- 2216089 TI - A new direction for dobutamine. PMID- 2216090 TI - Caring for the unwanted patient. PMID- 2216092 TI - Managing chronic pain with a permanent epidural catheter. PMID- 2216091 TI - Diabetes. Update 90. PMID- 2216093 TI - How managed care can work for you. PMID- 2216094 TI - Myocardial infarction. Pathophysiology, signs, and symptoms. PMID- 2216095 TI - Applauding the artistry of nursing. PMID- 2216096 TI - How a support group can help your chronically ill patient. PMID- 2216097 TI - 12 simple sensible steps for successful blood transfusions. PMID- 2216098 TI - Compulsive disorders. How to help when your patient has lost control. PMID- 2216099 TI - A.I.D.S. Update. PMID- 2216100 TI - Applying antiembolism stockings. PMID- 2216101 TI - [The World Conference on women, quite an event!]. PMID- 2216104 TI - [Law 145: a major reform]. PMID- 2216102 TI - [The point of Project 2000. Interview by Guylaine Chabot]. PMID- 2216103 TI - [Professional inspection in community health: an appreciable and appreciated impact]. PMID- 2216106 TI - The OIIQ: an organization for international cooperation. PMID- 2216105 TI - [Vulgarizing. Why? For whom? By whom? How?]. PMID- 2216107 TI - [Motivation of nursing personnel, program of interventions]. PMID- 2216109 TI - [Without a condom, the answer is no!]. PMID- 2216108 TI - [When it snows on the family]. PMID- 2216110 TI - [Bolivia. Few children survive]. PMID- 2216111 TI - Which women seek help for their psychiatric problems? AB - The avenues of help used by adult women with minor psychiatric morbidity were investigated in a random community survey from five Otago electoral rolls. A random subsample (n = 314) was subsequently interviewed in their homes. Information on a wide range of sociodemographic items pertinent to women's social roles was collected. Psychiatric illness was determined using a recognised structured diagnostic interview. Some 7.8% of the original population was found to have depressive, anxiety or phobic disorders at the symptom intensity level likely to be found in a psychiatric outpatient clinic. Of these women, just over one-third only (35%) said that they had sought help for their illness from any source. Most (86%) getting help received it from their general practitioner. However, unlike overseas studies where virtually all persons with psychiatric disorder consult their general practitioners for some reason, 13% reported that they had not visited their general practitioners at all in the preceding six months. Alternative therapies were infrequently sought. There was no evidence that health services were being inappropriately used by women with nonmedical problems. The results show that the majority of women are not getting treatments they require for their psychiatric illnesses. The low level of help seeking was particularly marked for young women. The findings suggest poor community awareness of the symptoms of minor psychiatric morbidity and the associated psychosocial consequences. PMID- 2216113 TI - Psoriatic arthritis: the use of disease suppressing agents in its management. PMID- 2216112 TI - Coronary heart disease among Pacific Island people in New Zealand. AB - Coronary heart disease is the leading cause of death in New Zealand. Death rates are higher among the Maori than the European population but rates have been declining in both groups over recent years. The occurrence of coronary heart disease among the Pacific Island population in New Zealand is unknown. Data from the National Health Statistics Centre (NHSC) and the Auckland coronary or stroke (ARCOS) study were used to describe the occurrence of coronary heart diseases among Pacific Island people. Age standardised mortality rates show that coronary heart disease is an important cause of death among Pacific Island men. Death rates have declined between 1973-77 and 1978-82 but this trend did not continue among men in the 1983-86 period. Age standardised mortality rates from coronary heart disease from the ARCOS data are 175/100,000 and 52/100,000 for Pacific Island men and women compared with 325/100,000 and 141/100,000 for Maori men and women. Age standardised rates for European men and women are 154/100,000 and 36/100,000 respectively. PMID- 2216114 TI - Hot water temperature in Dunedin homes with preschool children. AB - The mean temperature of the hot water supply of 62 randomly selected Dunedin homes with preschool children was 67.8 degrees C. More than 95% of the households visited had temperatures above the recommended temperature of 55 degrees C. The temperature was related to the socioeconomic status of the major earner of the household, the thermostat setting, the age of the water cylinder and its size. Accessible thermostats were of the water cylinder and its size. Accessible thermostats were only reliable in cylinders under 20 years old. PMID- 2216115 TI - Eye injuries in indoor cricket at Wellington Hospital: a survey January 1987 to June 1989. AB - About 30% of all sports injuries to the eye seen at Wellington Hospital are due to indoor cricket. An analysis of 29 eye injuries, January 1987 to June 1989 was carried out. Traumatic iritis, mydriasis and commotio retinae were the common injuries. There were eight blow out fractures of the orbit. Only two patients had permanent loss of vision due to choroidal tears with best vision in the damaged eye reduced to 6/9. A total of 88 eye clinic visits and 24 inpatient days were involved. The incidence of these injuries could be reduced by wearing eye and/or facial protection. PMID- 2216116 TI - Cycle helmet ownership in a birth cohort of children. PMID- 2216117 TI - The effect of benzalkonium chloride on the bronchodilator response to salbutamol nebuliser solution. PMID- 2216118 TI - Some gynaecological issues from a rural and Maori perspective. PMID- 2216119 TI - Contracts for general practitioners. PMID- 2216120 TI - Report on fitness of medical practitioners to defend charges. PMID- 2216121 TI - Lowering serum cholesterol levels. PMID- 2216123 TI - Specialist opinion and the ACC. PMID- 2216122 TI - Results of trials of screening. PMID- 2216124 TI - Annual practising certificate. PMID- 2216125 TI - Delays at the Medical Council. PMID- 2216126 TI - Conquest of the autoimmune diseases. PMID- 2216128 TI - Dietary intervention to reduce cot death. PMID- 2216127 TI - Rubella epidemic. PMID- 2216129 TI - Sarcoid myocarditis. PMID- 2216130 TI - Screening the elderly: a Christchurch study. AB - Two hundred and four people aged 65 year or older participated in a study to assess the merits of screening the elderly in a general practice. An average of 4.6 (SD 2.2) problems per patient were found. There was a mean of 1.1 (1.0) previously unrecognised problems per patient. Visual and hearing impairment, prostatism, incontinence and some neurological conditions were the main unrecognised problems. Those with unrecognised problems were older, less mobile and received more community supports. There was also a trend towards lower mental status questionnaire and functional scores and to greater medication usage. The results of this study support the principle of screening or case finding in the elderly. Targeting those at risk is required in order to reduce the workload involved. However, the current at risk indicators identified only a proportion of those in need of screening. Further research is required as to how to correctly identify these patients. PMID- 2216131 TI - Is the prevalence of bulimia nervosa higher among tertiary education populations? AB - In this study the prevalence of bulimia nervosa was estimated among 243 women in a tertiary educational setting. The results showed 43.6% (95% CI, 37.4 to 49.8) to report binge eating, the cardinal feature of bulimia nervosa, at some stage in the past and 2.5% (95% CI, 1.0 to 5.6) the full criteria for current bulimia nervosa. These figures are significantly higher than those reported recently for a general population sample in the same age range. Despite methodological differences between the two surveys the results give some support to claims that women in these settings are at a greater risk of developing eating disorders. PMID- 2216132 TI - Behind the iron mask: the mental changes of Parkinson's disease. PMID- 2216134 TI - Alternatives to the admission of some elderly patients to acute medical beds. AB - There is evidence that admission to an acute medical ward is not the best way to look after many elderly patients. This study investigated 83 general practitioners' preferences for the management of 200 elderly patients admitted to the medical beds at Wellington Hospital. For 63.5% of the patients this admission had been by their own doctor and 84% of these patients had been cared for by this doctor for longer than one year. Admission to an acute medical bed was the preferred option for only 48% of patients. Augmented home care was considered a possible option for 31.5% of patients but was mentioned as one of the preferred options for only 9.0%. Admission to a general practitioner bed was the preferred option for 16.5% of patients. The results of this study suggest that area health boards should provide more choices for the management of acute illness in elderly patients. PMID- 2216133 TI - Breast cancer incidence and mortality in Auckland, 1981-6. AB - Age standardised incidence and mortality rates were calculated for breast cancer for the Auckland area. Incidence of female breast cancer for 1981-4 was significantly higher in Auckland compared with all New Zealand, with a standardised incidence ratio of 1.11. While total incidence was the same across the three Auckland districts, there were wide discrepancies in mortality rates. Women in Takapuna had a far lower risk of dying of breast cancer compared with all New Zealand for 1981-6 and had a standardised mortality ratio of 0.86. Central Auckland and south Auckland women had increased risks--1.10 and 1.18 respectively. Similar discrepancies were evident in the important 45-64 age group. Possible reasons for the reported differences are discussed with socioeconomic factors seeming the most likely agency. PMID- 2216135 TI - Postviral myositis: case report. PMID- 2216136 TI - Blood glucose values in diabetic children at a camp. PMID- 2216137 TI - Selected problems in medical education. PMID- 2216138 TI - Risk factors for coronary heart disease in middle aged men. PMID- 2216139 TI - On sexually explicit questioning. PMID- 2216140 TI - Water associated infections. PMID- 2216141 TI - Spotting fad diets. PMID- 2216142 TI - Adverse drug reactions. PMID- 2216143 TI - Fluoridation and dental caries. PMID- 2216144 TI - The prescribing of mixtures. PMID- 2216145 TI - Trends in hepatitis B notifications. PMID- 2216146 TI - Psychologists and a code of ethics. PMID- 2216147 TI - Hours of work. PMID- 2216148 TI - Safe staffing. PMID- 2216149 TI - Party perspectives. PMID- 2216150 TI - Safety in the cancer ward. PMID- 2216151 TI - Nurses and equity issues. PMID- 2216152 TI - A social force. PMID- 2216153 TI - There is more than one use of SOAP. Subjective data, objective data, assessment and plan. PMID- 2216154 TI - Trends: shifting patterns of authority. PMID- 2216155 TI - What will physician payment reform mean for nurses? PMID- 2216156 TI - The impaired nurse--who is liable. PMID- 2216157 TI - What are user groups and how can they help you wield more power? PMID- 2216158 TI - Designing and implementing a supplemental staffing system. PMID- 2216159 TI - A hospital-based program for recovering chemically-dependent nurses. PMID- 2216160 TI - An agency-staffed nursing unit project. PMID- 2216161 TI - A program to manage nurse staffing costs. PMID- 2216162 TI - A psychiatric patient classification system. PMID- 2216163 TI - The excellence within. PMID- 2216164 TI - Recruitment: combining work and school. PMID- 2216165 TI - Traveling nurses--a valuable resource. PMID- 2216166 TI - Entry into practice. PMID- 2216167 TI - CC and med/surg nurses: another study. PMID- 2216168 TI - Policies and procedures: a synergistic approach. PMID- 2216170 TI - An innovative recruitment and retention scholarship program. PMID- 2216169 TI - Non-professional nursing staff attitudes about AIDS. PMID- 2216172 TI - Twelve-hour shifts: answer to job satisfaction? PMID- 2216171 TI - Clarifying resuscitation status: a new approach. PMID- 2216173 TI - Outpatient surgery: a case study. PMID- 2216174 TI - Watch your memo manners! PMID- 2216175 TI - Can LPNs start i.v.s in Ohio? PMID- 2216176 TI - OSHA and EPA--partners in our practice creating chaos. PMID- 2216178 TI - Dentistry 1980-89: a profession in transition. Percy T. Phillips memorial lecture 1990. PMID- 2216177 TI - Living wills--your right to die. PMID- 2216179 TI - Iconodontalgia V. PMID- 2216180 TI - Aspirin shown to increase P.O. facial swelling. PMID- 2216181 TI - Neuromuscular occlusion: diagnosing TMJ. PMID- 2216182 TI - Radiopharmaceuticals and Product Licences of Right. PMID- 2216183 TI - The current cost of nuclear medicine. AB - In the light of the control of expenditure and changes in radiopharmaceutical costs, changes in study protocols, new investigation procedures and inappropriate placing in Korner categories, the BNMS Council set up a working party to derive an agreed set of costings for Nuclear Medicine techniques. Using data from three hospitals with additional information from another nine, we have agreed the 1988 cost of individual nuclear medicine procedures in the UK. These figures include staffing (radiopharmacy, nursing, physics, medical including consultant), radiopharmaceuticals and other consumables, indirect costs (secretarial, administrative, portering), variable overheads (service contracts, stationery) and fixed overheads (rates, lighting, heating, building and engineering). Capital costs, equipment and buildings were not included. Because figures include salary and overhead costs they are difficult to compare with the majority of other previous nuclear medicine costings, apart from Bretland et al., or with data for other imaging modalities. Comparison of these costings with Korner schedules shows marked overlap between the Korner groups. Such groups therefore form a poor method of costing nuclear medicine procedures. We propose alternative groupings. PMID- 2216184 TI - Assessment of right ventricular function with nonimaging first pass ventriculography and comparison of results with gamma camera studies. AB - A new technique has been developed for measuring right ventricular function by nonimaging first pass ventriculography. The right ventricular ejection fraction (RVEF) obtained by non-imaging first pass ventriculography was compared with that obtained by gamma camera first pass and equilibrium ventriculography. The data has demonstrated that the correlation of RVEFs obtained by the nonimaging nuclear cardiac probe and by gamma camera first pass ventriculography in 15 subjects was comparable (r = 0.93). There was also a good correlation between RVEFs obtained by the nonimaging nuclear probe and by equilibrium gated blood pool studies in 33 subjects (r = 0.89). RVEF was significantly reduced in 15 patients with right ventricular and/or inferior myocardial infarction compared to normal subjects (28 +/- 9% v. 45 +/- 9%). The data suggests that nonimaging probes may be used for assessing right ventricular function accurately. PMID- 2216185 TI - The effect of forced expiration on the uniformity of 99Tcm-DTPA aerosol ventilation images in patients with excess sputum production. AB - This study examines the use of the forced expiratory technique (FET) as a means of improving the uniformity of radionuclide aerosol ventilation images in patients with excess sputum production. Ventilation images are objectively classified by two computer derived indices to characterize the degree of radioaerosol clumping and overall uniformity. In a series of twenty five patients with a long-standing history of daily sputum production, images acquired before and after forced expiration and again after a second ventilation immediately following FET showed no significant change in either index. The results obtained do not provide evidence to support the routine use of FET in conjunction with radioaerosol scintigraphy. The method of image classification correlates well with a visual assessment of image uniformity and has general application. PMID- 2216186 TI - Reclosure of disrupted abdominal incisions. AB - We evaluated prospectively a technique of delayed reclosure of disrupted abdominal incisions. Forty-one consecutive postoperative obstetric and gynecologic patients with abdominal incisions that had opened because of infection, hematoma, or seroma and had intact fascia participated in the study. All wounds were first managed identically, with surgical drainage and debridement, for a minimum of 4 days. The patients then were randomized to either wound reclosure by a standardized en bloc technique (35) or healing by second intention (six). Reclosure was successful in 30 of 35 cases (85.7%). The mean time to complete healing was 15.8 days in successful cases, 67.2 days in failed cases, and 23.2 days for all patients who were reclosed. Failure to heal after reclosure was due to subcutaneous infection in two patients and seroma in three; these women were significantly heavier than those in whom reclosure was successful. There were no other major complications of wound reclosure. Patients randomized to healing by second intention required a mean of 71.8 days of wound care. The time to complete healing in the wound-reclosure group was significantly shorter compared with the group that healed by second intention (P = .002, log rank test). We conclude that en bloc reclosure of disrupted surgical incisions, compared with nonsurgical treatment, significantly decreases the time required for wound healing and has minimal morbidity. PMID- 2216187 TI - Cefazolin for hysterectomy prophylaxis. AB - Efficacy data for single-dose cefazolin prophylaxis at hysterectomy are meager, and there are none evaluating the impact of route of administration on efficacy. For these reasons, 772 women undergoing elective abdominal or vaginal hysterectomy for benign diseases were given 1 g cefazolin either intramuscularly or intravenously in a randomized clinical trial. Preoperative diagnoses and clinical, surgical, and outcome variables were similar by route of administration for each surgical approach. Risk factors for infection after abdominal hysterectomy included younger age, lower postoperative hemoglobin concentration, and pelvic hematoma; women who developed infection after vaginal hysterectomy were heavier than those who remained uninfected and were more likely to have a pelvic hematoma. The overall incidence of major operative site infection requiring parenteral antimicrobial therapy in evaluable women was 7.2%: 7.6% for 539 women undergoing abdominal hysterectomy and 6.3% for 207 women undergoing vaginal hysterectomy. Postoperative infection was unrelated to route of cefazolin administration. PMID- 2216188 TI - Intraoperative radioimmunodetection of ovarian cancer using monoclonal antibody B72.3 and a portable gamma-detecting probe. AB - To assess the value of radioimmunoguided surgery in the intraoperative detection of ovarian cancer, we used monoclonal antibody B72.3, radiolabeled with 125I, and a hand-held gamma-detecting probe in 13 women with ovarian cancer undergoing exploratory laparotomy. B72.3, which recognizes a tumor-associated glycoprotein, TAG 72, was injected 12-29 days preoperatively (intraperitoneally in four cases, intravenously in nine, and by both routes in one). Intraoperatively, the abdomen was surveyed with the probe and probe counts were correlated with biopsies and excised specimens studied by routine histologic stains. Probe counts were positive in four of seven evaluable patients with histologically confirmed disease. In three of these four patients, the probe detected cancer in specimens interpreted as normal on frozen histologic sections. The probe also identified microscopic cancer in the one patient who had no gross disease. The specificity of the probe was 70%. Preoperative computed tomography was normal in all patients, including those with tumors as large as 3 cm. This pilot study shows the ability of radioimmunoguided surgery to detect occult ovarian cancer. PMID- 2216190 TI - Prognostic factors for outcome of and survival after second-look laparotomy in patients with advanced ovarian carcinoma. AB - In ovarian cancer stages IIB-IV, pre-treatment variables and variables obtained intraoperatively at second-look laparotomy were investigated for their prognostic influence on the outcome of 109 patients and survival after second-look laparotomy in 131 patients. The subjects came from a randomized trial of sequential versus alternating combination chemotherapy. The overall median survival after second-look laparotomy was 62 months. Logistic regression analysis identified stage and hysterectomy plus bilateral salpingo-oophorectomy and omentectomy as significant prognostic covariates for second-look laparotomy outcome. Based on a Cox multivariate stepwise analysis, independent prognostic factors for survival after second-look laparotomy were secondary residual tumor size, pre-treatment histologic differentiation grade, and performance status. A high differentiation grade and a good performance status at the start of therapy thus still had a prolonging effect on survival after second-look laparotomy. The prognostic power of these pre-treatment variables was increased substantially by the addition of the secondary residual tumor size variable. The 3-year survival rate after second-look laparotomy for high- and low-risk patients was 15 and 87%, respectively. Second-look laparotomy thus provides prognostic information in patients with advanced ovarian carcinoma, but the benefit in terms of survival is still unclear. PMID- 2216189 TI - Computed tomography-guided fine-needle aspiration of retroperitoneal lymph nodes in gynecologic oncology. AB - Computed tomography-guided fine-needle aspiration was performed on 30 retroperitoneal lymph nodes in 29 patients with gynecologic cancer. There were no serious complications. Review of the cytologic material demonstrated malignant cells in 83% of the aspirates. Because the predictive value of a positive aspirate approaches 100%, therapy for metastatic disease can be initiated in these patients with the need for an open biopsy. Among five aspirates in which malignant cells were not seen, the cellularity of the specimen appeared to be the critical factor determining the predictive value of the aspirate. Whereas neither of two patients with negative aspirates of adequate cellularity has developed recurrent disease, two of three patients with hypocellular negative aspirates have. Because a hypocellular negative aspirate from a retroperitoneal lymph node may not be a true reflection of disease status, either repeat aspiration or open biopsy is advisable. PMID- 2216191 TI - Ovarian metastases are rare in stage I adenocarcinoma of the cervix. AB - Over a 32-year period at the University of California, Los Angeles Medical Center, all cases of adenocarcinoma and adenosquamous carcinoma of the uterine cervix were reviewed to determine the incidence of ovarian metastases in stage I disease. One of 25 patients (4.0%) who underwent an exploratory laparotomy and radical hysterectomy had a microscopic ovarian metastasis. A literature review identified nine additional patients who had ovarian metastases and stage I adenocarcinoma of the cervix. Including our series, the overall reported rate of ovarian metastases is 1.8%. All ten patients had at least one of the following additional characteristics: They were postmenopausal, they had adnexal pathology, or they had positive pelvic lymph nodes. Thus, ovarian preservation is warranted in premenopausal patients who do not have ovarian pathology or evidence of other metastatic disease at surgery. Bilateral oophorectomy may be performed if frozen section examination of enlarged or suspicious nodes documents metastases. If the ovaries are left in the pelvis at the completion of the surgical procedure and microscopic spread to other pelvic tissues is documented, pelvic irradiation can be administered. PMID- 2216192 TI - The fallacy of the screening interval for cervical smears. AB - One hundred seventy-four women with invasive cervical carcinoma were interviewed about their cervical smear histories to assess the accuracy of self-reporting and to relate the smear history with patient and tumor characteristics. Patients reported significantly more frequent, more recent, and more normal smears than were documented in medical records. The interval between onset of cancer symptoms and previous smear correlated directly with advanced stage. Sixteen women with normal smears within 36 months had significantly more advanced cancers than did 25 women with recent abnormal smears. Women with recent normal and abnormal smears had similar sociodemographic and behavioral characteristics. Because of inaccuracies in patients' self-reported smear histories and cancers developing in women with recent normal smears, we conclude that a specific screening interval should not be relied upon. PMID- 2216193 TI - Cold-knife and laser conization for cervical intraepithelial neoplasia. AB - In a 5-year study, 425 women had conization performed for cervical intraepithelial neoplasia (CIN) I, II or III. Conization was performed only in cases of positive endocervical curettage or when colposcopy was inconclusive. In all other cases, local destruction was the operation of choice. In the early years of the study, conization was done by the cold-knife method (N = 201), whereas CO2 laser was used in the latter part of the study (N = 224). Success and complication rates were the same for the two methods. Abnormal cytology after conization was found in a total of 53 cases (12.5%), but a histologic confirmation of residual or recurrent CIN was made in only 27 women (6.4%). This corresponds to a success rate of 92% after cold-knife and 95% after laser conization. The CIN grading of the residual or recurrent CIN was similar to or less than the CIN diagnosis of the cone. Because our success rate was comparable to that of other series with much less strict referral criteria, our policy seems adequate. PMID- 2216194 TI - Postoperative urinary tract infection in gynecology: implications for an antibiotic prophylaxis policy. AB - A prospective observational study of postoperative infection after gynecologic surgery assessed the need for antibiotic prophylaxis with special reference to the urinary tract. Catheterization requirements in the postoperative period were compared with the development of urinary tract infection after excluding both preoperative and postoperative bacteriuria. Forty-six of 115 patients (40%) developed a urinary tract infection in the postoperative period. Furthermore, this was not clearly related to the need for postoperative catheterization. Significant wound and vaginal vault infections were uncommon, indicating that antibiotic prophylaxis should be directed specifically at the urinary tract. PMID- 2216195 TI - Primary invasive carcinoma of the vagina. AB - A retrospective review was conducted of 53 women with invasive carcinoma of the vagina and without documented exposure to diethylstilbestrol who were seen at the University of California Irvine Medical Center, Long Beach Memorial Medical Center, and Saddleback Memorial Medical Center from 1976-1988. Forty-seven (89%) had squamous cell carcinoma and six (11%) adenocarcinoma. Thirty-seven (70%) were treated with whole-pelvis irradiation and brachytherapy, nine with surgery alone, and the other seven with a combination of treatments. The crude and corrected 2 year survival rates for the entire group were 47 and 69%, respectively. Those with previous pelvic surgery were more likely to develop serious treatment related complications. There was a statistically significant correlation between previous hysterectomy and the diagnosis of primary invasive carcinoma of the vagina after the onset of symptoms. Women diagnosed during routine examination, before symptom onset, tended to have a survival advantage. All women, including those who have had hysterectomy, should be counseled to continue gynecologic cancer surveillance regardless of age. PMID- 2216196 TI - The effects of Chlamydia trachomatis on the female reproductive tract of the Macaca nemestrina after a single tubal challenge following repeated cervical inoculations. AB - The effects of repeated cervical infections followed by a single direct tubal inoculation with Chlamydia trachomatis, serovars D and F, were examined in 11 pig tailed macaques to test the hypothesis that tubal inoculation after cervical priming causes a more severe disease than primary tubal inoculation alone. Animals were cervically inoculated between two and five times. Fallopian tubes were inoculated with serovar D or F 1 week after the last cervical challenge. Three control monkeys received only one direct tubal inoculation without previous cervical inoculation. Infection was confirmed by isolating the microorganism from the endocervix in 13 of 14 monkeys and from the endosalpinx in four only after the tubal inoculation. Antibody was detected in post-infection sera of all 14. Tubal edema occurred in seven of 11 animals after the first cervical inoculation, and uterine erythema occurred in 11 of 11 after the second cervical inoculation. Peritubal adhesions were induced before the tubal inoculation in zero of seven given three or fewer cervical inoculations and four of four given five cervical inoculations (P less than .01). After direct tubal inoculation, peritubal adhesions became more prominent, and the 11 hysterectomy specimens showed plasma cell endometritis in nine and salpingitis in nine. Two control monkeys developed minor adhesions, the other none. One tube in two of three controls showed mild plasma cell infiltrates, whereas no evidence of endometritis was observed in controls. Histopathology in these monkeys was characteristic of chlamydial endometritis and salpingitis. However, the pathogenesis of these changes is uncertain because C trachomatis was not isolated from the endosalpinx after cervical inoculations alone. PMID- 2216197 TI - Torulopsis glabrata vaginitis: clinical aspects and susceptibility to antifungal agents. AB - Torulopsis glabrata is second only to Candida albicans in frequency of isolation from the vagina in both asymptomatic women and patients with yeast vaginitis. We retrospectively studied 33 patients from whom vaginal isolates of T glabrata were obtained. Torulopsis glabrata caused symptomatic vaginitis in 42% of the patients but was unassociated with symptoms in 30%; in 27% of patients, its importance was uncertain because of concomitant pathology. Antifungal susceptibility testing was performed on 39 T glabrata strains isolated from 39 patients. The minimal inhibitory concentrations (MICs) of the majority of T glabrata isolates fell within the sensitive range of the antimycotic drugs tested; however, no correlation was found between in vitro antifungal MICs and the response to azole drug therapy. Clinical success was achieved in 67% of the patients although mycologic cure occurred in only 33%. A small number of patients developed recurrent and often chronic Torulopsis vaginitis unresponsive to conventional therapy. Limited experience suggests that vaginal boric acid therapy may be of value in these recalcitrant cases. PMID- 2216198 TI - Topical podofilox for the treatment of condylomata acuminata in women. AB - The purpose of this study was to determine the efficacy and safety of 0.5% podofilox solution (Condylox) for the treatment of genital warts in women. Thirty seven women with anogenital warts applied the solution to the surface of these warts twice daily for 3 days, followed by 4 drug-free days. A minimum of two and a maximum of four treatment cycles were given. The subjects were evaluated weekly for the first 4 weeks and again at 6 and 10 weeks. At the end of 10 weeks, the mean number of warts per patient was reduced from 6.27 to 1.1, and half of the patients were completely cleared of warts. Only eight of 37 subjects (21.6%) developed new warts during the study period. Approximately 15% of patients reported "severe" local reactions to the treatment after the first treatment cycle, but this was reduced to only 5% by the last treatment cycle. During the same period, the patients reporting no side effects increased from 44 to 86%. The only woman who discontinued the study did so because of dizziness and epigastric discomfort, probably unrelated to drug use. Thus, 0.5% podofilox solution appears to be an effective treatment for condylomata acuminata, with acceptable side effects that are local and temporary. PMID- 2216199 TI - Does the treatment of genital condylomata in men decrease the treatment failure rate of cervical dysplasia in the female sexual partner? AB - Three hundred ninety women treated for cervical dysplasia by local tissue ablation were studied retrospectively to test the hypothesis that the treatment failure rate is lower if the male sexual partner is also treated. In 190 cases, the male sexual partner was examined and treated successfully for genital condylomata. Controls were 200 women treated during the same time period and closely matched to the study group regarding age, race, socioeconomic status, histologic grade of dysplasia, distribution of the lesions, and methods of therapy, but the male partner was neither examined nor treated. The treatment failure rate for women whose partners were also treated was not significantly different from that for women whose partners were not treated (6.8 versus 7.5%; P greater than .05), suggesting that treating genital condylomata in men does not affect the failure rate of cervical dysplasia in female sexual partners. PMID- 2216200 TI - Fetal acoustic stimulation as a possible adjunct to diagnostic obstetric ultrasound: a preliminary report. AB - Unfavorable fetal position during diagnostic obstetric ultrasound can interfere with visualization of certain structures, leading to prolonged or repeated examination. Fetal acoustic stimulation induces a fetal startle reflex and an increase in fetal movements. This report describes our experience with fetal acoustic stimulation to prompt fetal movement in an effort to improve fetal visualization. At gestational ages of 28 weeks or more a 94.1% success rate was noted, in 30 seconds or less in 70.6% of the cases. We conclude that fetal acoustic stimulation may be a valuable adjunct to diagnostic obstetric ultrasound. PMID- 2216201 TI - Premature rupture of membranes at term in nulliparous women: a hazard? AB - One hundred five consecutive women with premature rupture of the membranes (PROM) at term were managed expectantly for at least 24 hours. Seventy-six went into spontaneous labor, of whom 38 were augmented with oxytocin. Twenty-nine had labor induced. Subjects who delivered during the same study interval after artificial rupture of the membranes served as controls. There were no statistically significant differences in the frequency of amnionitis, endometritis, cystitis, neonatal infection, low Apgar score, low cord arterial blood pH, instrumental delivery, or cesarean delivery. Morbidity was seen most often in induced labor whether or not the membranes were ruptured for a long time. It is concluded that expectant management of PROM at term does not increase perinatal morbidity. PMID- 2216202 TI - Zinc status in women with premature rupture of membranes at term. AB - Zinc concentrations were measured by atomic absorption spectrometry in whole blood, scalp hair, pubic hair, and colostrum from patients at term with and without premature rupture of membranes (PROM). A maternal zinc index was established for each patient, expressed as an average ranking of the four determinations. The mean +/- SD value of the maternal zinc index in patients with PROM was significantly lower than in patients without this complication (4.33 +/- 1.18 versus 5.97 +/- 1.39, respectively; P = .0002). The inverse relationship between maternal zinc index and parity was statistically significant (r = -0.61; P = .04). These results suggest that the subnormal tissue zinc content in pregnancy may play a role as a causative factor in PROM at term. PMID- 2216204 TI - Pre-induction cervical ripening with prostaglandin E2 gel: intracervical versus intravaginal route. AB - The aim of our study was to evaluate the best method for cervical ripening before a classical induction with amniotomy and oxytocin. One hundred term pregnant patients who presented an unfavorable cervix and an indication for the induction of labor were assigned randomly to either 0.5 mg prostaglandin (PG) E2 gel intracervically (N = 52) or 3 mg PGE2 gel intravaginally (N = 48). The intravaginal gel had a greater effect on cervical ripening according to a modification of the Bishop score than did intracervical gel, but it had a higher incidence of side effects. PMID- 2216203 TI - Stripping membranes at term: can it safely reduce the incidence of post-term pregnancies? AB - Membrane stripping has been used clinically for many years but has not been well studied. An investigation was undertaken to determine whether weekly membrane stripping beginning at 38 weeks could safely reduce post-term pregnancies. One hundred eighty patients with firm gestational dates were randomized to either a treatment or control group. Control subjects received a gentle cervicovaginal examination each week to assess Bishop scores, whereas the treatment group also underwent weekly stripping of membranes. Women who received treatment had earlier delivery (mean +/- SEM 8.60 +/- 0.74 versus 15.14 +/- 0.83 days; P less than .0001) and fewer post-term deliveries than those in the control group (three versus 14; P less than .004). The reduction of post-term pregnancies was most notable in nulliparous women with unfavorable Bishop scores. Complications were similar in both groups. Membrane stripping was safe and was associated with earlier delivery and a decreased incidence of post-term gestation. PMID- 2216205 TI - Evaluation of a perinatal autopsy protocol: influence of the Prenatal Diagnosis Conference Team. AB - This study was designed to evaluate changes in the perinatal autopsy following the adoption of a new autopsy protocol. The University of Utah Medical Center has a Prenatal Diagnosis Conference Team composed of obstetricians, pediatricians, geneticists, and other health care professionals. These individuals are involved in the care of patients whose pregnancies are at risk for congenital malformations. An autopsy protocol was designed to increase the interaction of the pathologist with the Prenatal Diagnosis Conference Team in the evaluation of perinatal death. Two years, 1982 and 1987, before and after the protocol was implemented, were selected for retrospective review. The autopsies in 1987 made more specific diagnoses compared with those in 1982. Additional congenital anomalies were diagnosed, and increased numbers of patients were found to have well-described congenital disorders. The number of attempted postnatal autopsy chromosome studies increased and more chromosomal abnormalities were detected. The final autopsy diagnoses made in 1987 have provided more information to the physician for genetic or other patient counseling. After the protocol was adopted, increased numbers of cases were referred to the Medical Center for evaluation at autopsy. More of those who came to autopsy had been evaluated during life by members of the Prenatal Diagnosis Conference Team. Premortem sonograms had been done at an earlier gestational age and a greater number of anomalies were detected. Fewer of the fetuses had intrauterine death and more had pregnancy terminated by induction of labor. The gestational age at delivery declined. PMID- 2216206 TI - Prenatal administration of indomethacin as a tocolytic agent: effect on neonatal renal function. AB - Renal function was evaluated in premature infants whose mothers received long term indomethacin for tocolysis. Creatinine, urine and serum osmolalities, fractional excretion of sodium, and glomerular filtration rate were compared during the first 10 postnatal days in 14 preterm infants exposed to indomethacin in utero and in ten control infants. Renal function in both groups was comparable, with no significant differences on any study date in serum urea nitrogen and creatinine, ratio of urine osmolality to serum osmolality, fractional excretion of sodium, or glomerular filtration rate. These data suggest that long-term intrauterine administration of indomethacin does not significantly alter renal function. PMID- 2216207 TI - Enhanced anaphylatoxin and terminal C5b-9 complement complex formation in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelet count. AB - Complement activation was studied in ten consecutive pregnant women developing hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) and ten other women with normal pregnancies. Blood samples for anaphylatoxin (C3a/C3a desArg and C5a/C5a desArg) and terminal C5b-9 complement complex determinations were drawn at delivery and 24 hours and 7 days later. Women developing HELLP syndrome had higher plasma levels of anaphylatoxins with delivery than did women with uneventful pregnancies. The plasma levels of terminal C5b-9 complement complexes at the time of delivery were increased as compared with levels 1 and 7 days after delivery in women with HELLP syndrome. The plasma concentrations of the anaphylatoxins and the terminal C5b-9 complement complexes returned to normal levels within 1 week after delivery in the HELLP group. The formation of C5b-9 complement complex indicates that the terminal part of the complement cascade has been activated and that C5a has been formed and eliminated. Complement activation with release of anaphylatoxins and terminal C5b-9 complement complexes may be one etiologic factor behind the elevated blood pressure, hemolysis, liver insufficiency, and platelet consumption seen in these patients. PMID- 2216208 TI - Correlation between first- and early third-trimester glucose screening test results. AB - One hundred twenty-four normal gravidas had paired first- and early third trimester (26-32 weeks) 1-hour oral glucose screening tests performed. First trimester oral glucose screening test values correlated significantly with third trimester glucose screening test results for the entire population, for whites and non-whites, and for normal-weight and obese patients. First-trimester oral glucose screening test values at or below 110 mg/dL were seldom associated with third-trimester oral glucose screening test results at or above 135 mg/dL and were not associated with abnormal 3-hour glucose tolerance test (GTT) results. Nine of the gravidas (7.3%) were diagnosed with gestational diabetes mellitus during the third trimester, all of whom had first-trimester glucose screening test results above 110 mg/dL. The difference in incidence of gestational diabetes mellitus between gravidas having first-trimester glucose screening test results at or below 110 mg/dL (0%) and those having values above 110 mg/dL (16.4%) was highly significant (P less than .0001). For patients with first-trimester glucose screening test values at or below 110 mg/dL, third-trimester glucose screening may be unnecessary. In contrast, for gravidas having first-trimester glucose screening test results at or above 135 mg/dL, there is a high positive predictive value for elevated repeat glucose screening test results during the early third trimester. Patients having elevated first-trimester glucose screening values at or above 140 mg/dL are at particularly high risk for elevated glucose screening test results later in pregnancy and should forego repeat 1-hour third-trimester glucose screening in favor of a direct third-trimester 3-hour GTT. PMID- 2216209 TI - The twin-twin transfusion syndrome. AB - Twin-twin transfusion syndrome is a complication of monozygotic-monochorionic twinning with serious perinatal implications. An extensive literature review revealed that our current understanding of the anatomy and pathogenesis of the syndrome has not changed over the last 3 decades. However, modern diagnostic modalities, such as sonography and Doppler studies, allow antenatal diagnosis and therefore may change the current definition of the syndrome. Based on these data, a new composite definition of the syndrome is suggested. This definition includes the following criteria: 1) sonographic signs (inter-twin differences in abdominal circumference greater than 18 mm, polyhydramnios-oligohydramnios, and signs of monozygosity), 2) Doppler velocimetry of the umbilical arteries (inter-twin difference in systolic/diastolic ratios above 0.4), 3) demonstration of a transplacental vascular shunt, 4) inter-twin birth weight difference of 15% or more, and 5) inter-twin hemoglobin difference of 5 g/dL or more. In addition, prenatal diagnosis may help in the management of this complication, and it seems that intrauterine treatment of the placental vascular anomalies may be more effective than other antenatal therapeutic options. PMID- 2216210 TI - Carbon dioxide laser vaporization of diaphragmatic metastases for cytoreduction of ovarian epithelial cancer. AB - Three patients with International Federation of Gynecology and Obstetrics state IIIC ovarian adenocarcinoma underwent CO2 laser vaporization of large-volume (5-6 cm) and miliary right hemidiaphragmatic metastases at the conclusion of standard debulking surgery to effect optimal cytoreduction. Destruction of diaphragmatic metastases was accomplished rapidly with no added morbidity or blood loss. The hand-held CO2 laser is a useful modality for removal of isolated large- and small volume diaphragmatic disease, particularly if only the peritoneum is involved, and avoids the morbidity that may accompany entry into the pleural space. PMID- 2216211 TI - Enumeration of clue cells in rehydrated air-dried vaginal wet smears for the diagnosis of bacterial vaginosis. AB - Among 235 women attending an outpatient clinic, the diagnosis of bacterial vaginosis was made using three of the following four criteria: typical discharge, pH more than 4.5, positive amine sniff test, and clue cells in a wet smear. These findings were correlated with the finding of clue cells in air-dried wet smears rehydrated more than 1 month after the visit. The rehydrated specimens had the same microscopic appearance as a nonpreserved wet smear. The demonstration of clue cells in the rehydrated smears correlated with the composite diagnosis of bacterial vaginosis with a sensitivity of 96% and specificity of 98%. In a busy multi-physician setting, the scoring of clue cells in stored and rehydrated smears can be used to obtain consistent readings for wet-smear diagnostics, thus simplifying teaching and increasing the utility of wet smears in clinical research. PMID- 2216212 TI - Predicting preeclampsia. PMID- 2216213 TI - The length of uncomplicated human gestation. PMID- 2216214 TI - Transabdominal multifetal pregnancy reduction: report of 40 cases. PMID- 2216215 TI - Pregnancy complicated by preeclampsia-eclampsia with the syndrome of hemolysis, elevated liver enzymes, and low platelet count: how rapid is postpartum recovery? AB - The rapidity of postpartum disease recovery for severe preeclampsia associated with hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) has not been well studied. Between January 1980 and March 1989, 158 pregnancies with preeclampsia-eclampsia complicated by HELLP syndrome were managed at the University of Mississippi Medical Center. The 70 patients with platelet nadir below 50,000/microL (class 1 HELLP syndrome) required as long as 11 days for all members to achieve a platelet recovery concentration of more than 100,000/microL, whereas all 88 gravidas with platelet nadir between 50,000-100,000/microL (class 2 HELLP syndrome) exceeded this platelet concentration by the sixth postpartum day, a statistically significant difference (P less than .0001). The interval between delivery and the onset of diuresis (mean +/- SD) was significantly longer in class 1 than in class 2 patients with milder disease (22.7 +/- 18.9 compared with 15.9 +/- 11.1 hours). Significantly more postpartum days were required in class 1 than in class 2 HELLP parturients for the lactic dehydrogenase (LDH) concentration to decrease below 500 IU/L (4.2 +/- 4.9 compared with 3.2 +/- 2.7 days). No women in the class 2 group required plasma exchange therapy to effect disease arrest and reversal, but 11 of 58 severely ill women in class 1 were treated with this modality. We conclude that the platelet count and LDH serum concentration, as indicators of HELLP severity and recovery, are clinically useful tools and that a more protracted postpartum recovery period should be expected for progressively severe expressions of HELLP syndrome. PMID- 2216216 TI - Low-dose aspirin does not influence the clinical course of women with mild pregnancy-induced hypertension. AB - The effect of low doses of aspirin on women with mild pregnancy-induced hypertension was investigated by means of a prospective, randomized, double-blind trial. Forty-seven women hospitalized at 30-36 weeks' gestation because of mild pregnancy-induced hypertension were treated by a daily dose of either 100 mg aspirin or placebo. The mean blood pressure values, rates of development of severe preeclampsia, gestational ages at delivery, newborn weights, and 5-minute Apgar scores were similar in the aspirin-treated and the placebo-treated groups. We conclude that low-dose aspirin is not curative but is essentially a preventive treatment which, in order to be effective, should be started weeks before clinical signs of preeclampsia are present. PMID- 2216217 TI - Minor congenital malformations in infants of insulin-dependent diabetic women: association with poor glycemic control. AB - A prospective study of 171 insulin-dependent diabetic pregnant women was undertaken to establish the relationship of glycemic control with minor congenital malformations. Each live-born infant was assessed systematically by two independent examiners using a standardized checklist. There were 32 infants with minor congenital malformations (18.7%). There were significant differences in mean glycohemoglobin A1 between the group with minor congenital malformations and the group without congenital malformations at 12, 16, and 20 weeks, but not at 8 or 24 weeks. Logistic regression analysis showed that maternal age, race, gravidity, White class, duration of diabetes, maternal vasculopathy, and cigarette smoking were not significant variables correlated with minor congenital malformations. Because glycohemoglobin levels from 12-20 weeks are believed to reflect glycemic control from approximately 6-20 weeks, we conclude that poor glycemic control during late embryogenesis and early fetal development is associated with an increased risk of minor congenital malformations. We speculate that improvement of glycemic control during this period should decrease the risk of minor congenital malformations. PMID- 2216218 TI - Vaginal birth after cesarean delivery: results of a 5-year multicenter collaborative study. AB - Cesarean delivery has become the most frequently performed major operation in the United States. Widespread use of vaginal birth after previous cesarean delivery could potentially eliminate up to one-third of cesareans. However, many physicians have been reluctant to adopt this policy without large studies conclusively demonstrating its safety. This study evaluated the maternal and perinatal outcomes of over 5000 cases of labor after previous cesarean delivery. This multicenter study began in 1984 and initially included nine California hospitals. During the first 2 years, there were 1776 trials of labor resulting in 1314 vaginal births. In January 1986 two additional hospitals joined the collaborative project. Over the next 3 years, there were 3957 trials of labor resulting in 2977 vaginal births at the 11 participating hospitals. During the entire study period, 5733 patients opted for a trial of labor and 4291 (75%) delivered vaginally. There were no maternal deaths in the trial-of-labor group, and perinatal mortality was not significantly different from that of the general obstetric population. These results support the findings of numerous smaller studies that have concluded that the policy of routine repeat cesarean delivery should be abandoned. PMID- 2216219 TI - Real-time microcomputer-based analysis of spontaneous and augmented labor. AB - In an attempt to develop a reproducible, objective measure of adequate uterine activity in labor, real-time measurements of intrauterine pressure amplitude and contraction frequency, interval, duration, and integral were made in 54 patients, 11 of whom received oxytocin augmentation. We determined the active pressure integral required per centimeter of cervical dilatation, expressed in kPa seconds, and the mean active pressure, expressed in kPa. The augmented group had a significantly higher mean active pressure integral per centimeter than those in normal labor (P less than .01). There was a trend, which did not reach statistical significance, for subjects who required oxytocin augmentation of labor to develop a higher mean active pressure than those in normal labor. However, the correlation of any uterine contractility index (Montevideo units, Alexandria units, mean active pressure) with progress in labor was poor. We conclude that women with dysfunctional labor require more uterine activity for progress in labor than women with normally progressing labor, and that the computer-derived "area under the curve" is not a better predictor of labor progress than Montevideo units. PMID- 2216220 TI - Accuracy and safety of transvaginal sonographic placental localization. AB - Transvaginal sonographic localization of the placenta was performed in 100 patients suspected of having placenta previa. Except in one patient, the diagnosis was confirmed at cesarean delivery in all cases of placenta previa found by sonography before delivery, resulting in a 93.3% predictive value of a positive test. The predictive value of a negative test was 97.6%; in two patients a low-insertion placenta diagnosed by sonography was found to be a placenta previa at delivery. The sensitivity and specificity of the technique were 87.5 and 98.8%, respectively. Although in some instances transvaginal sonography was performed during vaginal hemorrhage, aggravation of bleeding was never observed. Transvaginal sonographic localization of the placenta proved to be an accurate and safe diagnostic procedure. PMID- 2216221 TI - The relationship of unwed status to infant mortality. AB - We studied the impact of unwed status on infant mortality in the state of Iowa, where obstetric and newborn care is readily accessible. Our purpose was to document the extent of the contribution of unwed status to infant mortality and to compare unwed gravidas with their married counterparts. We hoped the comparisons would provide information that could be used for future programs of prevention. Our data encompassed a 10-year period (1977-1986) during which the incidence of infant deaths occurring in offspring of unmarried women was significantly greater than expected. The unwed population commonly consisted of younger, poorly educated, primigravid women who frequently did not seek prenatal care. We suggest that personal factors inherent in this group of women may be more operative than lack of access to perinatal care in determining pregnancy outcome. We believe our data underscore the need to redouble efforts to prevent unintended pregnancy. PMID- 2216222 TI - Prenatal diagnosis of congenital toxoplasmosis. AB - Prenatal diagnosis of congenital toxoplasmosis was attempted in 50 pregnant women at risk for giving birth to an affected child. Fifteen of these patients seroconverted during pregnancy and 35 had a high initial antibody level in their first serum sample. Prenatal diagnosis consisted of a combination of ultrasound screening, amniocentesis, and funipuncture at about 20 weeks' gestation. Diagnosis of congenital toxoplasmosis was based on a positive toxoplasma culture of amniotic fluid or fetal blood and on the presence of specific immunoglobulin M antibodies in fetal blood. In addition, alterations in fetal hematology, cellular immunology, and fetal liver tests were indicative of infection. Fetal infection was detected in six fetuses; two died in utero as a consequence of the infection and four were born after 37 weeks' gestation. Despite antibiotic treatment with pyrimethamine and sulfadiazine, one child has internal hydrocephalus and chorioretinitis and another has unilateral chorioretinitis. In the two other children, the disease is still subclinical. Of the 44 children born after a negative prenatal diagnosis, 35 have reached the age of 1 year; toxoplasma antibodies have disappeared in all of them. Investigation of the remaining nine children showed a decrease in toxoplasma antibodies, suggesting that none of them are affected. Prenatal diagnosis was never associated with fetal loss, and premature delivery occurred in only two cases. We conclude that prenatal diagnosis of congenital toxoplasmosis is safe and reliable. PMID- 2216223 TI - Fructosamine compared with a glucose load as a screening test for gestational diabetes. AB - Five hundred seven women were screened for gestational diabetes between 20-36 weeks' gestation. All received a 100-g glucose (polycose) load at 28 weeks with measurement of plasma glucose 1 hour later. Fructosamine levels were measured at 4-week intervals from 20-36 weeks. At 36 weeks, a full 100-g 3-hour glucose tolerance test was performed on all subjects. Eighteen women were diagnosed as having gestational diabetes. The glucose load had a sensitivity of 81% in detection of gestational diabetes, compared with 50% for fructosamine at 36 weeks. Fructosamine is not useful as a screening test for gestational diabetes as currently defined. PMID- 2216224 TI - Production of prolactin by cultures of isolated cells from human first-trimester decidua. AB - An enriched fraction of first-trimester decidual cells that synthesize and release prolactin (PRL) was obtained by discontinuous Percoll gradient (20-50%) centrifugation of collagenase type I- and deoxyribonuclease I-dispersed cells (3 mg/mL and 50 micrograms/mL, respectively). Centrifugation of the cell suspension yielded three major bands aggregating at the density interfaces. The fraction of the 30-40% Percoll interface contained enlarged decidual cells and constantly secreted significant amounts of PRL into the medium for at least 10 days. The fraction of the 40-50% Percoll interface contained fibroblastic cells and secreted a small amount of PRL into the medium. Cells in the other fractions did not attach to the plastic dishes in 48 hours. Under the influence of progesterone (100 ng/mL), the cultured decidual cells retained their capability of PRL production for at least 10 days because no decline of the secretion rate was observed. The culture system established by the present study is satisfactory for investigating decidual cell functions, including the regulatory mechanisms of PRL production. PMID- 2216225 TI - In vitro fertilization in unstimulated cycles: a clinical trial using hCG for timing of follicle aspiration. AB - In vitro fertilization (IVF) was performed in normally ovulatory women after the follicular phase of an unstimulated cycle. Twenty patients initiated 36 cycles of unstimulated IVF, with serial ultrasound examinations and hCG 10,000 IU given when the follicle was mature. Thirty aspirations were carried out under intravenous sedation with transvaginal ultrasound guidance. One or more oocytes were obtained in 29 aspirations (97%) for a total of 52 oocytes (average 1.7); 37 fertilized (71%), two were polyspermic, and 35 cleaved (67%). Seventeen aspirations (57%) yielded multiple oocytes. All 25 oocytes obtained from dominant follicles fertilized (100%), and 12 of 27 oocytes from secondary follicles fertilized (44%) (P less than .05 versus dominant follicles), with one polyspermic fertilization in each group. Sixteen cycles resulted in a single embryo transfer (ET), eight had two embryos, and one had three embryos transferred (36% multiple ET). Five clinical pregnancies (20% per ET, 17% per retrieval) resulted in four ongoing pregnancies (16% per ET, 13% per retrieval), all singletons. Our results suggest that in selected cases, IVF in unstimulated cycles may be a clinically viable alternative to stimulated cycles, with preliminary success rates in the range of national averages for stimulated cycles. PMID- 2216226 TI - Effect of peritoneal fluid from endometriosis patients on endometrial stromal cell proliferation in vitro. AB - Late proliferative phase endometrial stromal cells grown in short-term culture were used as a model for the stromal component of endometriotic implants. Cells were grown in medium alone and in medium supplemented by 5, 10, and 20% concentrations of the cell-free fractions of peritoneal fluid obtained from patients with and without endometriosis. Nine fluid-sample pairs were matched based on the presence or absence of endometriosis at laparoscopy and the similarity of peritoneal fluid estradiol concentrations. Stromal cell proliferation as reflected by 3H-thymidine incorporation during sequential cell harvests over 72 hours was greater for cells exposed to endometriosis peritoneal fluid than for those exposed to non-endometriosis peritoneal fluid. This reached statistical significance with exposure to peritoneal fluid concentrations of 10 and 20% (P less than .05). A linear dose-response relationship between 3H thymidine incorporation and peritoneal fluid concentration could be derived only for stromal cells exposed to fluid samples obtained from endometriosis patients (r = 0.51; P less than .001). In addition, proliferation over 72 hours was significantly greater for cells grown in 20% endometriosis peritoneal fluid than for those grown in nutrient medium alone (P less than .001). These data imply that factor(s) secreted into the peritoneal fluid of endometriosis patients may play a role in the proliferation or maintenance of disease implants. PMID- 2216227 TI - Control of immediate postoperative pain with topical bupivacaine hydrochloride for laparoscopic Falope ring tubal ligation. AB - Conflicting reports exist in the literature on the effectiveness of topical local anesthetic applied to the serosal surface of the fallopian tubes for the control of immediate postoperative pain after mechanical (band or clip) tubal ligation. Sixty-four patients were studied prospectively during outpatient laparoscopic Falope ring tubal ligation using the modified McGill Present Pain Intensity Scale. Patients randomly assigned to four groups received topical bupivacaine hydrochloride on both fallopian tubes, the right tube only, or the left tube only, or received none (controls). A unique study design was incorporated which allowed the untreated fallopian tube to serve as a within-subject control for each patient receiving unilateral treatment. Statistical analysis confirmed significant benefit when both fallopian tubes were treated as compared with no treatment (P less than .05). There was also consistent evidence of decreased immediate postoperative pain perception on the treated side for patients receiving unilateral treatment. The value of topical bupivacaine was demonstrated by both subjective patient response (McGill Pain Scale) and reduced need for pain medication before outpatient discharge. Our data support the value of topical bupivacaine applied to the serosal surface of the fallopian tubes for the reduction of postoperative pain after outpatient laparoscopic mechanical (band or clip) tubal ligation. PMID- 2216228 TI - Effect of a single dose of oral pseudoephedrine on uterine and fetal Doppler blood flow. AB - Pseudoephedrine, a stereoisomer of ephedrine with alpha- and beta-adrenergic properties, is the active ingredient in over-the-counter oral decongestants. Its safety during pregnancy has not been studied adequately. The purpose of this investigation was to evaluate the effects of pseudoephedrine on uterine and fetal Doppler blood flows. Twelve healthy pregnant women between 26-40 weeks' gestation ingested a standard 60-mg dose of pseudoephedrine. A pulsed Doppler system was used to perform blood flow measurements of the uterine arcuate artery, fetal aorta, and umbilical artery before dosing, immediately thereafter, and at 15 minute intervals during the first 3 hours after drug ingestion. Blood flow velocities were not altered significantly after dosing in either the maternal or fetal circulation. In no case did absolute fetal or uterine blood flow velocities decrease significantly or systolic/diastolic ratios persistently elevate to abnormal values. We conclude that no significant alterations in the uterine or fetal circulations occur after the ingestion of a single dose of oral pseudoephedrine by healthy pregnant patients in the third trimester. PMID- 2216229 TI - Single dose of nifedipine in normotensive pregnancy: nifedipine concentrations, hemodynamic responses, and uterine and fetal flow velocity waveforms. AB - The short-term effect of 20 mg of oral nifedipine on maternal and fetal hemodynamics was investigated in ten healthy, normotensive women at 38 weeks' gestation admitted to the hospital for elective cesarean delivery. Within 1 hour after nifedipine administration, mean arterial pressure had decreased by 10% and a slight increase was observed in maternal heart rate. A statistically significant (P less than .01) decrease in the systolic-diastolic ratio was found in the flow velocity waveform from the uterine artery, but no change was seen in that from the arcuate artery. No changes were observed in the fetal heart rate pattern or in umbilical or thoracic aortic flow velocity waveforms. Nifedipine concentrations in the mother had no correlation with maternal or fetal hemodynamic responses. At delivery 2.5 hours after nifedipine ingestion, the umbilical venous-maternal ratio of nifedipine concentrations was 0.76. PMID- 2216230 TI - The development of fetal heart rate patterns during normal pregnancy. AB - Characteristics of the fetal heart rate (FHR) were studied longitudinally throughout the second and third trimesters in 43 low-risk singleton fetuses. The second trimester was characterized by an FHR pattern showing minimal differences between quiet and active intervals of fetal behavior. Few movements were accompanied by accelerations of small magnitude. Brief decelerations of variable magnitude exceeded the number of accelerations, and their frequency declined with advancing maturity. The percentage of body movements accompanied by FHR acceleration, the amplitude of these accelerations, and the rate of rise in heart rate increased with gestational age. Up to 30 weeks, the characteristics of the baseline FHR were similar in both periods of fetal rest and activity, with the baseline variability becoming significantly greater with advancing gestation. However, during quiet cycles of fetal behavior after 30 weeks, the baseline variability became progressively narrower, so that in late pregnancy different behavioral states could be determined reliably from characteristics of the baseline FHR alone. PMID- 2216231 TI - The occurrence of simultaneous fetal heart rate accelerations in twins during nonstress testing. AB - A prospective study was performed of 152 pairs of nonstress tests (NSTs) obtained simultaneously from both members of 52 twin gestations. Fifty-seven percent of the total fetal heart rate (FHR) accelerations occurred simultaneously in both twins. Between twins, the incidence of simultaneously occurring FHR accelerations was independent of gestational age, growth discordancy, or the type of placenta. For each twin, the number of FHR accelerations remained constant with increasing gestational age. These results may suggest that tactile communication exists in utero between twins. PMID- 2216232 TI - "Macrosomic" twinning: a study of growth-promoted twins. AB - We evaluated 56 twin pregnancies representing the tenth decile of the mean twin birth weight distribution to investigate whether larger twins face the same increased perinatal risk as do macrosomic singletons. Compared with pregnancies in the ninth decile, no significant difference was found between the means of maternal age, parity, and gestational age; between the rates of presentation combinations and cesareans; or between the neonatal sex ratios. However, the incidence of growth-discordant pairs was significantly higher in the heavier group (P = .034). Compared with the general twin population, the tenth-decile group contained significantly fewer primiparas (P = .0023). Maternal obesity and diabetes were infrequent and could not explain the increased birth weight. The neonatal outcome was excellent. Although the comparison revealed insignificant differences, it is possible that the combination of higher parity, malpresentation rate, and male-to-female ratio may be operative in the genesis of large twins. PMID- 2216233 TI - Increased cell adherence of group B streptococci from preterm infants with neonatal sepsis. AB - Most women with group B streptococcus cervical colonization have uncomplicated pregnancies, but about 1% experience preterm premature rupture of membranes (PROM) followed by neonatal group B streptococcal sepsis. In such cases, streptococcal adherence to and penetration of the membranes may be an important step in the pathogenesis. In the present study, chorionic epithelial cells were incubated with group B streptococci isolated from either children developing sepsis after preterm PROM (complicated pregnancies) or from uncomplicated pregnancies. Incubation periods varied. The numbers of adherent bacteria per chorionic epithelial cell were counted by microscopic examination. After 70 minutes' incubation, the number of adherent group B streptococci in complicated pregnancies was 38, compared with 14 in uncomplicated pregnancies (P less than .001). This difference in vitro might reflect the virulence of group B streptococci. PMID- 2216234 TI - Antepartum and intrapartum events in women exposed in utero to diethylstilbestrol. AB - Using a retrospective cohort design, we analyzed the effects of intrauterine diethylstilbestrol (DES) exposure on various antepartum and intrapartum events. Gravidas exposed to DES had a higher likelihood of being delivered abdominally, undergoing manual removal of the placenta, and hemorrhaging in the postpartum period. The increased risk for these events remained after controlling for age, race, and parity. We also constructed labor curves in DES-exposed women by plotting cervical dilation against time. The curves were similar for nulliparous DES-exposed women and nulliparous controls, but DES-exposed parous women experienced prolonged labors. These findings suggest that, in addition to the well-known adverse effects of intrauterine DES exposure, the interaction between the uterus and placenta is altered in some DES-exposed patients. PMID- 2216236 TI - Quality assurance indicators and short-term outcome of hysterectomy. AB - Fifteen gynecologic quality assurance indicators recently published by The American College of Obstetricians and Gynecologists were applied to a previously reported hysterectomy data base. Chart reviews were performed for the most recent 257 cases in the data base, representing an 18-month interval. The indicators were divided into two groups: those intended to identify morbidity and mortality and those intended to screen for appropriateness of care. Rates of actual morbidity and cases that failed to meet published criteria sets for hysterectomy were determined by chart review regardless of the presence of a quality assurance indicator. A total of 135 indicators were identified in 114 (44%) of the 257 cases, including 64 patients (25%) with morbidity indicators and 50 (19%) with appropriateness indicators. Actual morbidity was correctly identified in all 64 cases in which morbidity indicators were present. Three cases with significant morbidity were identified by chart review but not identified by the indicators, yielding positive and negative predictive values of 100 and 98%, respectively, and an overall accuracy of 99% for morbidity indicators. By contrast, 14 of the 50 cases in which appropriateness indicators were present actually failed to meet published criteria sets. An additional seven cases failing to meet criteria sets were identified by chart review and not identified by the indicators, yielding a positive predictive value of 28%, a negative predictive value of 97%, and an overall accuracy of 83% for appropriateness indicators. PMID- 2216237 TI - Anatomy of anal sphincters and related structures in continent women studied with magnetic resonance imaging. AB - Five anally continent nulliparas of reproductive age were studied with magnetic resonance imaging. The internal and external anal sphincters could be easily delineated, as could the intervening longitudinal musculature, puborectalis muscle, anococcygeal raphe, anorectal lumen, vagina, uterus, bladder, urethra, coccyx, and pubis. The shape of the sphincters was nearly cylindrical, with an anterior component averaging 18.3 mm thick and 28.0 mm long. Fifty-four percent of this anterior thickness was attributable to the internal sphincter. The anorectal angle varied considerably, with a mean of 86.8 +/- 19.1 degrees (range 60-112). The angle between the portion of the rectal lumen supported by the anococcygeal raphe, or levator plate, and the plane of the puborectalis muscle was consistent at 149.0 +/- 6.3 degrees (138-154). The finding of anterior anal sphincters with substantial thickness and length contrasts markedly with a view often pictured in the literature of a female anal sphincter that narrows anteriorly to half its posterior length and forms a small bundle of muscle rather than a broad band. Knowledge of these relationships is important in primary repair of obstetric sphincter lacerations as well as in surgical correction of anal incontinence. PMID- 2216235 TI - Removal of large symptomatic intrauterine growths by the hysteroscopic resectoscope. AB - Fifty-three patients underwent 55 procedures with a resectoscope for the removal of large symptomatic intrauterine growths. The presenting complaint was menorrhagia, menometrorrhagia, or heavy postmenopausal bleeding in 38 patients; excessive menses plus infertility in 13 patients; and infertility alone in two patients. Forty-three patients had pedunculated or sessile submucous myomas and ten patients had large endometrial polyps. The long-term results are based on 45 patients followed for longer than 1 year. Excessive bleeding was controlled in 40 of the 43 women (93%). Failure to control abnormal bleeding was apparent within the first year. Seven of the 12 infertility patients (58%) delivered live-born infants. Five patients have undergone subsequent hysterectomies (9%). Two patients had repeat resectoscopic removal of myomas and two had subsequent non resectoscope myomectomies. No major complications were encountered. PMID- 2216238 TI - Detection, prevalence, and prognosis of asymptomatic carcinoma of the cervix. AB - Between 1979-1986, 82 of 407 patients (20%) treated for infiltrative carcinoma of the cervix were asymptomatic at the time of diagnosis. Sixteen (20%) of these 82 patients had stage IA, 60 (73%) had stage IB, and six (7%) had stage IIA disease. Asymptomatic patients represented 16 of 23 (70%) of stage IA, 60 of 196 (31%) of stage IB, and six of 77 (8%) of stage IIA. In the Netherlands, population screening for cervical carcinoma is conducted on women aged 35-55 years. To examine the prevalence of asymptomatic cervical carcinoma and the way in which it was detected in different age groups, we studied the patients referred to our department. Among the patients younger than 35 years with cervical carcinoma, 20 of 70 (29%) were asymptomatic with disease detected by incidental screening, whereas eight of 177 (5%) in the group 55 years or older had been detected by incidental screening. In the age category 35-55 years, 54 of 160 (34%) were asymptomatic. Patients aged 35-55 years had undergone population screening or incidental screening. In the patients 55 years or older, asymptomatic disease was significantly less prevalent than in younger patients. Only one of the 66 asymptomatic patients in stage IB or higher suffered tumor recurrence. Among symptomatic patients, 25 of 136 (18%) with stage IB and 17 of 71 (24%) with stage IIA had tumor recurrence. Despite the favorable prognosis of patients with asymptomatic carcinoma, asymptomatic presentation could not be shown to be a significant prognostic factor, as were tumor diameter and lymph node status. PMID- 2216239 TI - Primary mass closure of midline incisions with a continuous polyglyconate monofilament absorbable suture. AB - Mass closure of midline incisions with a running large-bore permanent monofilament polypropylene suture has been used in general surgery and gynecology patients with a reported small incidence of fascial dehiscence. Late-occurring wound sinus formation is one problem reported with the use of this permanent suture material. Over a 22-month period, 285 patients had midline incisions closed with a continuous, running no. 1 polyglyconate monofilament delayed absorbable suture. Closely spaced bites (about 1.5 cm apart) were taken and placed 2 cm lateral to the fascial edge. Over 60% of the patients had surgery because of gynecologic cancer. Other high-risk factors included obesity in 62%, diabetes in 19%, and previous irradiation or chemotherapy in 22%. An ovarian cancer staging procedure was done in 16% of the patients. Of the remaining patients, almost half had extensive operative procedures that ranged from exenterations to hysterectomies with lymph node dissection. Wound complications were noted in nine patients (3.2%). Seven had superficial infections, one had an evisceration, and one developed a ventral hernia. Wound sinuses did not occur. The closure technique is safe and expedient and distributes tension equally over a continuous line. It has the additional advantage of eventual absorption of the suture material, thereby avoiding the wound sinus problems occasionally reported with large-bore permanent sutures. PMID- 2216240 TI - Experimental and clinical studies with radiofrequency-induced thermal endometrial ablation for functional menorrhagia. AB - A method of ablating the endometrium has been introduced into clinical practice that uses radiofrequency electromagnetic energy to heat the endometrium, using a probe inserted through the cervix. Preliminary studies suggest that over 80% of patients treated will develop either amenorrhea or a significant reduction in flow. The advantages of radiofrequency endometrial ablation over laser ablation or resection are the avoidance of intravascular fluid absorption, simplicity (no special operative hysteroscopic skills are required), speed of operation, and reduced cost compared with the Nd:YAG laser. In this paper, we describe the experimental studies performed during development of this new technique. PMID- 2216241 TI - A rapid method for detection of group B streptococcal colonization: testing at the bedside. AB - Vertical transmission of group B streptococci, the most frequent cause of early neonatal sepsis, can be interrupted by intrapartum antibiotics. However, rapid methods for detecting colonized women must be developed to limit the administration of antibiotics to those who are at risk of delivering an infected infant. The accuracy of a colorimetric test using starch serum medium on vaginal and rectal specimens from women with preterm labor or prolonged rupture of membranes was evaluated. The test was interpreted by labor and delivery room nurses without special microbiologic training. Starch serum medium results were compared with those obtained from routine cultures. Thirteen of 29 positive vaginal cultures (45%) and eight of 18 positive rectal swabs (44%) were identified by nurses using the rapid method. This was significantly different (P less than .001) from sensitivities of 93 and 95%, respectively, for the same vaginal and rectal specimens interpreted by a bacteriology technologist. The specificity for the test from both sites was 95% for the nurses. The sensitivity was 53 and 36% for vaginal and rectal swabs, respectively, for a subgroup of mothers whose infants were assessed as clinically septic. The low sensitivity of starch serum medium as interpreted by nurses in the labor suite is inadequate to allow the test to replace cultures in identifying women colonized with group B streptococci. Efforts to increase the sensitivity should be directed toward improving nursing staff interpretation rather than improving the medium itself. PMID- 2216243 TI - Blood transfusion in contemporary obstetric practice. PMID- 2216242 TI - Window operation: an alternative treatment method for Bartholin gland cysts and abscesses. AB - Recently, we developed the "window operation" as a more effective way to treat Bartholin gland cysts and abscesses. The window operation was used to treat 25 Bartholin cysts and 22 Bartholin abscesses during a 3-year period from October 1, 1986 to September 30, 1989. Under local anesthesia, a small piece of skin including the cyst wall was excised in an oval shape, and suturing was performed along the excised margin. Postoperative antibiotics were given in cases of acute inflammation. A new mucocutaneous junction was observed at the 4-week postoperative checkup. No complications or recurrences have been observed during the study period. The window operation can be an alternative method of treatment for Bartholin gland cysts or abscesses. PMID- 2216244 TI - Acute pyelonephritis in pregnancy: a prospective study of oral versus intravenous antibiotic therapy. PMID- 2216245 TI - Transvaginal sonographic detection of the pseudogestational sac associated with ectopic pregnancy. PMID- 2216246 TI - Serum CA 125 levels in early pregnancy and subsequent spontaneous abortion. PMID- 2216247 TI - Variability of serum prolactin and progesterone levels in normal women: the relevance of single hormone measurements in the clinical setting. PMID- 2216248 TI - Amoxicillin therapy for Chlamydia trachomatis in pregnancy. PMID- 2216249 TI - Evidence of gonadal and gonadotropin antibodies in women with a suboptimal ovarian response to exogenous gonadotropin. PMID- 2216250 TI - Pregnancy after successful vaginoplasty and cervical stenting for partial atresia of the cervix. AB - We previously reported surgical correction of vaginal agenesis and partial cervical atresia in an 11-year-old girl with amenorrhea and a pelvic mass. This patient, the subject of this report, conceived 7 years later and delivered at term. An abdominal cerclage was placed at 12 weeks' gestation to protect the cervix, and delivery was by cesarean. PMID- 2216252 TI - Prolapse of a neovagina created by self-dilatation. AB - In patients with congenital absence of the vagina, a neovagina may be created by either operative or nonoperative techniques. A 25-year-old patient with a neovagina created by self-dilatation developed complete prolapse of the neovagina with an enterocele. A transabdominal sacral colpopexy successfully suspended the vaginal vault and allowed the patient to resume sexual function. PMID- 2216251 TI - Successful pregnancy after ZIFT in a patient with congenital cervical atresia. AB - We report the third patient with a successful pregnancy following operative correction of congenital cervical atresia. The pregnancy was achieved through zygote intrafallopian transfer (ZIFT). Although stenosis of the newly formed cervical canal causes considerable morbidity, therapy should be aimed at the creation of a conduit for menstrual blood and for possible future pregnancy. New techniques in assisted reproduction such as in vitro fertilization-embryo transfer, gamete intrafallopian transfer, and ZIFT increase the chances of pregnancy in patients with congenital cervical atresia. A hysterectomy, as advocated until very recently, should not, in our opinion, be the first treatment of choice. PMID- 2216253 TI - Vaginal mullerian cyst presenting as an anterior enterocele: a case report. AB - A case is discussed of an extremely large vaginal mullerian cyst that presented as an anterior enterocele. Sonographic and radiologic studies are described. The patient underwent operative excision of the cyst with reconstructive vaginoplasty. PMID- 2216254 TI - Ovarian suspension in massive ovarian edema. AB - Massive ovarian edema is an uncommon condition found in young women that is speculated to occur as a result of incomplete ovarian torsion. We present the second patient to our knowledge to undergo ovarian suspension as a treatment for this condition. This approach succeeded after ovarian wedge resection had failed. Our patient remained symptom-free at 1 year of follow-up. Ovarian suspension should be considered when this pathologic entity is diagnosed. PMID- 2216255 TI - Septic shock complicating drainage of a Bartholin gland abscess. PMID- 2216256 TI - Rectovulvar fistula in a child secondary to an unusual foreign body. AB - Foreign bodies in the female genital tract are well recognized as a cause of pain, discharge, secretions, and infection. In the small child, the presence of a vaginal discharge is usually associated with either a common object which has been inserted or sexual abuse complicated by a sexually transmitted disease. A 3 year-old child presented with a recurrent labial secretion and drainage due to an unusual foreign body. It was only during a second operation that the possibility of a foreign body was entertained, and diagnostic testing was begun. A third operation permitted removal of the foreign body, a large bone probably of animal origin. The fistula tract was closed after a colostomy was performed. This represents the first reported case of a rectovulvar fistula not of a congenital nature. PMID- 2216257 TI - Combined vesicovaginal-ureterovaginal fistulas associated with a vaginal foreign body. AB - A case is presented of vesicovaginal-ureterovaginal fistulas associated with a neglected vaginal foreign body. The patient complained of a foul-smelling vaginal discharge and was found to have a 4-cm hard vaginal mass on examination. Urinary incontinence developed subsequently. Examination under anesthesia was performed, and an aerosol deodorant cap was operatively removed from her posterior vagina/perirectal space. Subsequent work-up demonstrated the presence of both a vesicovaginal fistula and a right ureterovaginal fistula. The patient underwent a combined vaginal repair of the vesicovaginal fistula and abdominal ureteroneocystostomy. The frequency, types, etiology, and treatment of genitourinary fistulas are reviewed with particular attention to those associated with a vaginal foreign body. PMID- 2216258 TI - Clomiphene citrate stimulation as an adjunct in locating ovarian tissue in ovarian remnant syndrome. AB - Ovarian remnant syndrome results from residual ovarian tissue after bilateral oophorectomy. The syndrome is associated with chronic pelvic pain and is suspected when premenopausal levels of FSH and LH are present in a patient with documented bilateral oophorectomy. Histologic demonstration of ovarian tissue at operation confirms the diagnosis. We treated a patient with ovarian remnant syndrome with a 10-day course of clomiphene citrate, 100 mg daily, to stimulate the residual ovarian tissue and facilitate localization. Preoperative ultrasound revealed a 5.0 x 3.5 x 6.2-cm cystic mass in the right adnexal region. Exploratory laparotomy easily localized the mass, and it was removed intact. Histologic slides demonstrated normal ovarian tissue with multiple follicles in various stages of development and a corpus luteum cyst. Clomiphene citrate is capable of stimulating an ovarian remnant, producing an enlarged, cystic structure easily localized by ultrasound. The increased size and preoperative knowledge of the location facilitated surgical removal. PMID- 2216259 TI - Giant-cell arteritis of the uterus with associated temporal arteritis: a case report. AB - Giant-cell arteritis involving the uterus was identified incidentally upon hysterectomy and anterior colporrhaphy for uterine prolapse. Subsequently, the patient was found to have giant-cell temporal arteritis presenting with fever of unknown origin. Fourteen previous cases involving the female genital tract have been reported. There appears to be an association between constitutional symptoms of fever, weight loss, malaise, headache, and polymyalgia rheumatica in elderly women with uterine prolapse and giant-cell arteritis of the genital tract. The rare presentation of giant-cell arteritis in the female genital tract does not support invasive costly evaluation in asymptomatic patients. However, a thorough investigation for involvement of other sites, including appropriate treatment for generalized disease, should be undertaken. PMID- 2216260 TI - Preoperative angiographic uterine artery embolization in the management of cervical pregnancy. AB - The diagnosis of a cervical ectopic pregnancy is often made intraoperatively in the presence of extensive hemorrhage during attempted evacuation. In some cases, hysterectomy has been the necessary treatment to control bleeding. We report two cases of cervical pregnancy detected by ultrasound. Before pregnancy termination, the uterine arteries were successfully embolized using angiographic techniques. As a result, surgical evacuation was performed with minimal hemorrhage; hysterectomy was not required and the patients' potential fertility was retained. PMID- 2216261 TI - Angiographic arterial embolization and computed tomography-directed drainage for the management of hemorrhage and infection with abdominal pregnancy. AB - Hemorrhage during or after surgery, pelvic abscess, bowel obstruction, and prolonged febrile morbidity can complicate the puerperal course of the gravida after removal of an extrauterine fetus with nondisturbance of the extrauterine placenta. In this report we describe the successful angiographic arterial gelfoam embolization of the placental vascular bed to control heavy postoperative hemorrhage in a mother suffering adult respiratory distress syndrome after removal of the fetal portion of her abdominal pregnancy. Six weeks later, computed tomography (CT)-directed drainage by catheter of a placental abscess was performed. Selective angiographic transcatheter embolization with gelfoam is a useful tool for the control of hemorrhage in the gravida who is an unfavorable operative candidate or who may present technical hemostasis problems peculiar to the placenta with abdominal pregnancy. Later use of CT-directed catheter drainage of the infected residual placental mass provided a nonoperative means of treatment. PMID- 2216262 TI - Monozygotic twins discordant for partial trisomy 1. AB - A 25-year-old primigravida delivered monozygotic twins discordant for multiple anomalies and partial trisomy 1 mosaicism. The phenotype of partial trisomy 1 includes craniofacial, central nervous system, and ocular anomalies. The most likely explanation for these findings is that the translocation occurred after twinning occurred. This observation emphasizes that monozygotic twins are not necessarily genetically identical. They are identical at conception, but subsequent mutation and rearrangement of the genome may cause substantial phenotypic differences. PMID- 2216263 TI - Fetal posterior urethral valve syndrome: a prospective application of antenatal prognostic criteria. AB - A case of posterior urethral valve syndrome is presented. Four weeks after a normal 24-week ultrasound examination, diminished amniotic fluid, megacystis, and renal hyperechogenicity were observed. A repeat ultrasound examination at 30 weeks' gestation identified oligohydramnios and increased renal echogenicity. These findings prompted the performance of a percutaneous cystocentesis to assess fetal renal function indirectly. The specimen was evaluated for osmolality and sodium and chloride concentrations. The urine electrolyte concentrations (sodium 115 mEq/L; chloride 93 mEq/L) and the osmolality (230 mOsm/L) were elevated, suggesting impaired renal function and a poor prognosis. Despite these findings, aggressive management was used, including administration of antenatal corticosteroids and elective preterm delivery. A percutaneous cystocentesis was required during the infant's initial resuscitation, followed by a difficult urethral catheterization. Ultimately, a vesicostomy performed on day 4 of life was associated with prompt return of renal function (serum creatinine 0.7 mg/dL at the time of discharge). At 6 months of age, normal renal function has been documented and the vesicostomy has been closed. This case demonstrates the potential limitations of available prognostic criteria in evaluating fetal urinary obstruction and residual renal function. In selected cases (when the onset of obstruction is documented in the third trimester), refinement of these prognostic criteria may be indicated. Similar cases may be best managed by preterm delivery and prompt postnatal decompression. PMID- 2216264 TI - Congenital chyloperitoneum as a cause of isolated fetal ascites. AB - Isolated fetal ascites is an unusual prenatal finding and must be differentiated from immune and nonimmune hydrops. This entity is most commonly associated with gastrointestinal and genitourinary anomalies. Fetal chyloperitoneum, however, should be considered as a possible cause. Pulmonary hypoplasia and abdominal dystocia during attempted vaginal delivery are potential complications. We present a case of isolated fetal ascites due to congenital chyloperitoneum. PMID- 2216265 TI - Ascites not due to congestive heart failure in a fetus with lupus-induced heart block. AB - Hydrops developing in fetuses with lupus-associated heart block has usually been assumed to result from congestive heart failure. We present a case in which fetal ascites associated with complete heart block resolved promptly after administration of betamethasone and prednisone to the mother, who had anti-SSA and who developed clinical lupus erythematosus. This resolution occurred with no demonstrable change in fetal cardiac function. We conclude that an immune mechanism, rather than congestive heart failure, was responsible for the fetal ascites. PMID- 2216266 TI - TRAP sequence--successful outcome with indomethacin treatment. AB - A case of twin reversed arterial perfusion (TRAP) sequence (acardiac twin) complicated by hydramnios was managed by maternal administration of indomethacin. Successful outcome was achieved after 8.5 weeks of therapy with delivery of a normal live-born infant at 34 weeks. PMID- 2216267 TI - Contemporary management of a potentially lethal fetal anomaly: a successful perinatal approach to epignathus. AB - Prenatal diagnosis of epignathus (a teratoma originating in the oropharynx) has been reported previously. However, in many of these cases the neonates succumbed to acute respiratory distress secondary to airway obstruction at the time of birth. We describe a case of antepartum diagnosis of epignathus using ultrasonography and magnetic resonance imaging as complementary techniques. The ability to accurately define the fetal anomaly permitted us to plan a unique strategy for peripartum management. After cesarean delivery of the infant from the uterus, the umbilical cord was not clamped and the fetoplacental circulation was left undisturbed. A tracheostomy was then performed, after which the umbilical cord was clamped and the infant was stabilized. Several hours later, a debulking procedure was performed in the operating room to remove the tumor from its attachment to the bony palate. Both mother and infant did well postoperatively. The ability to plan and perform a controlled tracheostomy while the infant remained oxygenated and ventilated proved to be lifesaving in this case. PMID- 2216268 TI - Fetomaternal bleeding as a cause of recurrent fetal morbidity and mortality. AB - A woman had fetomaternal bleeding of unknown cause during at least three of five pregnancies. Each event was associated with significant fetal morbidity or mortality. Although fetomaternal bleeding has been reported as a cause of unexplained fetal death, its occurrence in subsequent pregnancies has not been described previously. PMID- 2216269 TI - Ongoing fetomaternal hemorrhage treated by serial fetal intravascular transfusions. AB - Nonimmune hydrops secondary to atraumatic, massive fetomaternal hemorrhage was diagnosed at 33.5 weeks' gestation by a maternal Kleihauer-Betke stain, confirmed by funipuncture. The initial fetal hematocrit was 6.5%. Kleihauer-Betke testing revealed a fetomaternal hemorrhage of approximately 230 mL. Fetal karyotype, total immunoglobulin M, and liver function tests were normal. Maternal parvovirus serology was negative. Treatment with two fetal intravascular transfusions provided only transient improvement because the fetomaternal hemorrhage proved to be unrelenting. PMID- 2216270 TI - Pregnancy associated with Friedreich ataxia. AB - The pregnancy of a woman with Friedreich ataxia was complicated by the onset of preterm labor and preeclampsia. Administration of magnesium sulfate (MgSO4.7H2O) in the usual intravenous dosage resulted in the dramatic development of profound motor weakness and respiratory distress. Magnesium acts to antagonize the action of acetylcholine at the motor end plate of the neuromuscular junction and may operate synergistically with underlying neuromuscular disorders. Therefore, the use of magnesium sulfate in patients with Friedreich ataxia and other similar neurodegenerative diseases is contraindicated. PMID- 2216271 TI - Successful pregnancy outcome in association with lipoatrophic diabetes mellitus. AB - Lipoatrophic diabetes mellitus is a rare syndrome characterized by lipoatrophy and insulin-resistant diabetes mellitus. Partial lipodystrophy without clinical diabetes mellitus has been associated with intrauterine growth retardation and fetal death. We report successful pregnancy outcomes in two women with lipoatrophic diabetes mellitus. PMID- 2216272 TI - Use of magnetic resonance imaging in the diagnosis of cortical blindness in pregnancy. AB - Magnetic resonance imaging (MRI) may be helpful in the assessment of eclampsia and preeclampsia with central nervous system symptomatology such as cortical blindness. We describe a rare case of complete binocular blindness postpartum with no other neurologic deficits, in which MRI abnormalities were undetected on computed tomography. The better soft-tissue discrimination of MRI may visualize important but subtle lesions which ultimately may help to explain the underlying pathophysiologic mechanism in such cases. PMID- 2216273 TI - Diabetes insipidus associated with craniopharyngioma in pregnancy. AB - A case is presented of a pregnancy complicated by a suprasellar mass diagnosed at 27 weeks' gestation. This patient developed diabetes insipidus, which was successfully treated with 1-desamino-8-D-arginine vasopressin. Thyrotropin releasing hormone and ACTH stimulation tests were also abnormal, requiring the institution of thyroid and cortisol replacement therapy. The patient was delivered at 34 weeks' gestation secondary to worsening visual field testing. A craniotomy was performed in the postpartum period with removal of a craniopharyngioma. With successful medical treatment and careful observation, surgical intervention may be postponed until postpartum or until a gestational age with lower neonatal morbidity and mortality is reached. PMID- 2216274 TI - Immune hydrops fetalis attributable to anti-HJK. AB - We describe a new low-frequency antigen as the cause of immune hydrops fetalis in a fetus presenting at 27 weeks with a hematocrit of 6%. The fetus was treated successfully by intravascular transfusion. This antigen, temporarily identified as HJK, has been detected in only one family. PMID- 2216275 TI - Infant survival following delayed postmortem cesarean delivery. AB - A 19-year-old multipara was delivered of a living infant by postmortem cesarean 22 minutes after documented maternal cardiac arrest and 47 minutes from the fatal injury. Neonatal follow-up at 18 months of age demonstrated no evidence of neurologic damage. PMID- 2216276 TI - Fetal levels of tobramycin following maternal administration. AB - A single dose of tobramycin 2 mg/kg was given intravenously to a woman who presented a 22-week heterotopic pregnancy with both intrauterine and ovarian gestations and two living fetuses. After excision of the adnexum, tobramycin levels were measured in the maternal serum and in the fetal fluids and tissues. Antibiotic levels were especially high in the fetal spleen and kidney. PMID- 2216278 TI - Worry over new HIV testing kit sales legislation. PMID- 2216277 TI - Umbilical cord hematoma following diagnostic funipuncture. AB - Major complications associated with funipuncture have been reported but are rare. This is a report of a diagnostic funipuncture performed on a 29-week fetus with a single umbilical artery and multiple malformations. Immediately after the procedure, a voluminous hematoma developed at the site of needle insertion in association with a severe fetal bradycardia. Fetal death was confirmed within 5 minutes of needle insertion. It is hypothesized that the risk of complications of funipuncture may vary according to the clinical indication for the procedure and may be increased in the presence of certain fetal malformations. The rapid evolution of complications, as occurred in the present case, underlines the importance of having a clear plan of management in the event of mishap and discussing this plan with the parents before undertaking diagnostic funipuncture. PMID- 2216279 TI - Health promotion--the OHN's role. PMID- 2216280 TI - Cancer of the skin. PMID- 2216281 TI - BSE. An unlikely zoonosis. AB - It will probably be some years before we can be certain whether bovine spongiform encephalopathy (BSE) can be transmitted to humans. What steps should workers who come into contact with cattle take to protect themselves now? PMID- 2216282 TI - Absenteeism or ill health?--a fatal change of mind. AB - Following a fair and appropriate procedure before dismissing an employee is vitally important. The procedures for ill health dismissals are very different from those for absenteeism cases. PMID- 2216283 TI - First aid courses. PMID- 2216284 TI - Asbestos control buyer's guide. PMID- 2216285 TI - EPA study supports smoking ban. PMID- 2216286 TI - Surgical workers' AIDS risk studied. PMID- 2216288 TI - Workers entering confined spaces must choose appropriate respirator. PMID- 2216287 TI - Prevention of reproductive disorders requires more research, vigilance. PMID- 2216289 TI - Data systems help define relation between exposure, health effects. PMID- 2216290 TI - Gerontological certification. PMID- 2216291 TI - Breast cancer among women from Gothenburg with regard to age, mortality and coexisting benign breast disease or leiomyoma uteri. AB - The entire female population of Gothenburg, aged 20 years or above as of November, 1969 (n = 162,449), was studied for virtually all inpatient hospital admissions in 1970-1979 with breast cancer (n = 2,411). After the vital status as of December, 1984 had been traced, cases of fetal (n = 1,502) and of nonfatal (n = 909) breast cancer were separated. A search for coexisting benign breast disease and leiomyoma uteri yielded significant recordings of disease association exclusively with nonfatal breast cancer. PMID- 2216292 TI - Investigations of coagulation system and fibrinolysis in patients with disseminated adenocarcinomas and non-Hodgkin's lymphomas. AB - Indicating activation of coagulation fibrinopeptide A (FPA) was elevated in 80.1% (mean = 10.5 ng/ml; P less than 0.01) and thrombin-antithrombin III complexes in 58.3% (TAT; mean = 5.3 ng/ml; p less than 0.05) in patients with adenocarcinomas (n = 57). In patients with non-Hodgkin's lymphomas (n = 30), however, elevation was observed only in 66.6% (FPA) and in 42.8% (TAT). Incidence of thrombosis is high only in the first group Local fibrinolysis explains elevated D-dimer in adenocarcinomas (1,818 ng/ml; p less than 0.01) and in non-Hodgkin's lymphomas (576 ng/ml; p less than 0.05). Significantly increased t-PA antigen was not committed by adequately increased t-PA activity in adenocarcinomas, because of high levels of the acute-phase protein, plasminogen activator inhibitor (mean = 25.3; p less than 0.01), indicating systemic hypofibrinolysis. Hemostatic disorder in patients with malignancy can be attributed to a combination of acute phase reaction and an activation of coagulation. PMID- 2216293 TI - Cerebrospinal fluid content of manganese, platinum, and strontium in patients with cerebral tumors, leukemia, and other noncerebral neoplasms. AB - Electrothermal atomic absorption spectrophotometry was employed to measure the concentrations of manganese, platinum, and strontium in the cerebrospinal fluid (CSF) of 47 patients with brain neoplasms (34 benign and 13 malignant), 17 leukemic patients, 10 patients with lymphoma or non-cerebral solid tumors, and 27 control patients. According to the data obtained, manganese appears to be significantly (p less than 0.015) depleted from the CSF of leukemic patients, whereas platinum is diminished in CSF of patients with brain tumors, leukemia, lymphoma, or noncerebral solid tumors; the ratios for the mean CSF concentration of platinum in these tumor patients/control patients ranged between 0.52 and 0.7. There was no significant difference in CSF concentrations of strontium among the groups examined. PMID- 2216294 TI - Application of monoclonal antibodies in diagnosis of human breast cancer by fine needle aspiration cytology. AB - In the present study the authors have examined 100 breast nodules by fine-needle aspiration cytology (FNAC) using the avidin-biotin complex method of immunoperoxidase staining. The monoclonal antibodies (MAbs) employed, B 6.2 and B 72.3, recognize two distinct molecules expressed by transformed breast epithelium. The authors have compared this immunocytochemical reaction with the conventional cytology and the histological examination as well. The data of the MAbs alone or in combination have been evaluated in terms of sensitivity, specificity, predictive value and test efficiency. The results show that tumor cells are strongly reactive with the MAbs. So the authors believe that this method in conjunction with conventional cytology may be useful in the diagnosis of breast tumor, especially in doubtful FNAC. PMID- 2216295 TI - Plasma melatonin in patients with breast cancer. AB - Daytime plasma melatonin values were measured by radioimmune assay in 86 patients with breast cancer; 280 assays were done and compared with the clinical status of the patients. Patients in the advanced disease group had significantly higher levels than those in the adjuvant treatment group, and patients with progressive disease had significantly higher values than those in remission or with stable disease. No significant differences were found between different dominant metastatic disease sites. Multiple-regression tests showed a significant inverse correlation between survival and melatonin values. PMID- 2216296 TI - A pilot study of metoclopramide, dexamethasone, diphenhydramine and lorazepam in prevention of nausea and vomiting in cisplatin-treated male patients. AB - In a pilot study we evaluated the efficacy and tolerability of a four-drug antiemetic combination (metoclopramide, dexamethasone, diphenhydramine and lorazepam) in cancer patients submitted to cisplatin chemotherapy at doses greater than or equal to 50 mg/m2. Fifty male patients entered the study. Complete protection from vomiting and nausea was obtained in 41 patients (82%) (95% confidence limits 71 and 93%). Toxicity was slight except for moderate sedation in 10% of patients necessitating their hospitalization. Only one extrapyramidal reaction (akathisia) was observed. When these results were compared to our previous experience in male patients treated with a combination of metoclopramide, dexamethasone and diphenhydramine without lorazepam, used at the same doses and schedule, no clear benefit and higher toxicity was observed. PMID- 2216297 TI - Clinical correlations with chemosensitivities measured in a simplified tritiated thymidine incorporation assay in patients with malignant effusion. AB - Utilizing a simplified tritiated thymidine incorporation assay, in vitro chemosensitivity of tumor cells obtained from malignant effusions was assessed and, in these patients, chemotherapeutic drugs were administered directly into the peritoneal or pleural cavity. Then, correlations between in vitro sensitivity and clinical response were investigated. Fifteen (88%) of 17 patients with various carcinomas gave evaluable chemosensitivity results. All 15 patients were evaluable for in vitro-in vivo correlations. This assay had an accuracy of 75% for prediction of response (3 of 4) and an accuracy of 82% for prediction of resistance (9 of 11), when the peak achievable plasma concentrations were selected as the concentrations used for in vitro sensitivity testing, adopting 80% inhibition of thymidine incorporation as cutoff level. PMID- 2216299 TI - Comparative phase II study of idarubicin versus doxorubicin in advanced breast cancer. AB - The aim of the present study is to confirm the antitumor activity of orally administered idarubicin (IDA) in patients with advanced breast cancer. Doxorubicin (ADRIA) was chosen as control treatment and the patients were randomized to receive either IDA or ADRIA according to a 2:1 ratio. Sixty-three patients, 77% of whom were pretreated with chemotherapy excluding anthracyclines, entered the study. The doses were: IDA 45 mg/m2 orally on 3 consecutive days every 28 days: ADRIA 75 (60) mg/m2 intravenously every 21 days. A complete + partial response (CR + PR) was observed in 11/37 (30%) evaluable cases treated with IDA and in 6/19 (32%) cases treated with ADRIA. If all the patients were included, the CR + PR remission rates were 27.5 and 27%, respectively. There were no significant differences as regards time to remission, duration of remission and survival. None of 10 cases who crossed over the treatments responded to the second therapy. The most frequent side effects of IDA were myelosuppression and nausea/vomiting. The only significant statistical difference between the two anthracyclines was the lower incidence of alopecia after IDA. Although there were 3 cases of cardiotoxicity after ADRIA, 2 of which severe, no case of clinical cardiotoxicity was observed after IDA. The present study confirms that orally administered IDA is an active agent in advanced breast cancer. PMID- 2216298 TI - 'Two-route chemotherapy' using cisplatin and its neutralizing agent, sodium thiosulfate, for intraperitoneal cancer. AB - The pharmacokinetics of intraperitoneal cisplatin (DDP) administered with simultaneous intravenous sodium thiosulfate (STS) were investigated by a bioassay system using the phytohemagglutinin (PHA) stimulation assay of human peripheral blood mononuclear cells (PBM). Active DDP in the plasma, assessed by the bioassay system, was almost completely inactivated, when the level of STS in the plasma was more than 500 times higher at molar STS/DDP ratios than that of DDP. However, the peak level of active DDP in the peritoneal cavity was not significantly decreased. Fourteen patients with intraperitoneal carcinoma were treated with intracavitary DDP chemotherapy in combination with STS in this setting. Of 8 patients with malignant ascites who were evaluable for response, 4 patients experienced complete disappearance of ascites and the remaining 4 patients responded with apparent decrease in the volume of their ascites. No serious drug associated toxicity was encountered. PMID- 2216300 TI - Studies on the antineoplasticity of Schiff bases containing 5-nitrofuran and pyrimidine. AB - Antineoplastic properties of different Schiff bases obtained by the interaction of 5-nitrofuran with substituted pyrimidines have been examined both in vitro and in vivo. In vitro studies on L 5178Y/asparaginase sensitive, HL 60 and P 388 cell lines and in vivo studies on the P 388 cell line indicate that all the compounds are potential antineoplastic agents. However, 2-(5-nitro-2-furfurylidene-amino) pyrimidine (SBP1) is the most effective, and 2-(5-nitro-2-furfurylidene-amino)-6 hydroxypyrimidine (SBP3) is the least effective agent. Doubling time, rates of protein and DNA synthesis inhibition and LD50 values-1,000 mg/kg body weight for SBP1 and 1,275 mg/kg body weight for 2-(5-nitro-2-furfurylidene-amino)-4- methylpyrimidine (SBP2)- in the oral route support the activity and use of SBP1 and SBP2 as future anticancer agents. PMID- 2216301 TI - Relation between age and blast cell differentiation in acute myeloid leukaemia patients. AB - The relation between age and the cytological and cytochemical features of blast cell differentiation in 211 patients with primary acute myeloid leukaemia (AML) was investigated. Five cytological and cytochemical features of blast cell differentiation-the presence of Auer rods, the presence of granules, low nuclear/cytoplasmic ratio, Sudan black positivity and the maturation index-were studied in bone marrow smears of each AML patient. The results showed significantly more AML cases with both cytological and cytochemical features of blast cell differentiation in young patients (less than 60 years old) than in elderly patients (greater than 60 years old). These findings support the existence of two forms of primary AML: one more frequently detected in younger patients with more differentiated blast cells and the second with less differentiated blast cells mainly found in elderly patients. PMID- 2216302 TI - Influence of iron on proliferation and cell cycle kinetics on cultured malignant and nonmalignant cells. AB - The presence of an iron-containing complex (FSC, ferric sorbitol citrate) in medium inhibited proliferation of malignant (KB. GHC) cells: but did not appreciably alter the proliferation of normal (HBS, Vero) cells. Flow cytometric analysis showed considerable differences of malignant and normal cell growth kinetics. With addition of 200 microM Fe in FSC, malignant cell proliferation was suppressed. An increased number of cells in G1 and early S phase suggested that iron excess blocked the cell cycle before beginning of DNA synthesis. PMID- 2216303 TI - The problems in the arrangement of the azygos vein. AB - The azygos veins in thirty six cadavers (26 adult bodies, 10 human fetuses) were examined with special reference to the correlation with the midline of the vertebral column. The azygos veins were often observed to cross the middle of the ventral side of the vertebral column from right to left, and the occurrence of this crossing to the left is more frequent than that previously described- occurring in twenty two of the adult bodies. In three of the adult bodies, the vein ran upwards along the midline. In the remaining adult, the azygos vein ascended on the right side only of the vertebral column. In the fetuses, no azygos vein crossed the midline and the vein lay only on the right side or along the midline of the vertebral column. these results indicate the possibility of leftward displacement of the azygos vein during the aging process. PMID- 2216304 TI - The postnatal development of the mouse pericardium; the time and mechanism of formation of pericardial pores. AB - The mouse pericardium is a continuous serous membrane, up to postnatal day 6 (P6), that consists of pericardial and pleural mesothelia with sparse connective tissue sandwiched in between. This study shows that on P7 the pericardium becomes fenestrated, and the pericardial and pleural cavities become continuous. We found that the number of pores per pericardium increased continuously with the advance of age and reached as many as 3000 on P21. Transmission electron microscopy of the pericardium revealed various structures of the pericardial and pleural mesothelia that may relate to the formation of the pericardial pores. The pericardial and pleural mesothelia were adjoined with cytoplasmic processes that extended toward the base of the opposing mesothelium. As a result of the adjoinment, a pair of U-shaped folds were formed. The two U-shaped folds were connected with tight junctions at their apices, and separation of these junctions may give rise to the pericardial pores. PMID- 2216305 TI - Differentiation of the brain stem reticular formation in the triturus, Triturus pyrrhogaster. AB - The brain stem of the triturus was observed to be initially composed exclusively of the mantle layer. A few days before hatching, a narrow marginal layer differentiated peripherally. At the time of hatching, the marginal layer was clearly visible throughout the brain stem, except for in a medial region of the optic tectum. Approximately one week after hatching, a few cells migrated into the marginal layer, and almost simultaneously, a few fibers in that layer were myelinated. Cells migrating into the marginal layer formed reticular neurons as well as the raphe nuclei and superficial cellular layers of the optic tectum. As the development proceeded, the number of myelinated fibers in the marginal layer increased, and cells in that layer, especially reticular neurons, were seen to be embedded among numerous myelinated fibers, assuming the characteristic features of the reticular formation. PMID- 2216306 TI - Fibrous structure of the joint capsule in the human shoulder. AB - The fibrous structure and arrangement of joint capsules of human shoulders [8 males (7 right, 6 left), 4 females (4 right, 3 left)] were observed under a low magnification microscope as well as a polarized microscope on film preparations (Hautchen-Praparat, Vogt 1935) with reference to stained sections (mainly with H, E and orcein). The joint capsule is composed of synovial and fibrous layers and is classified into three types according to tissue composition [areolar (loose connective tissue-Fawcett, 1986) type, fibrous (dense fibrous- Fawcett, 1986) type and adipose type- (Key 1932)]. In the joint capsule of the shoulder, the areolar type was found in the anterior region, and the fibrous type in the posterior, superior and inferior regions; the adipose type was not found. The author found that the fibrous layer of the fibrous type basically has a 3 layered structure; the composition and arrangement of fibers differ depending on the type of layer. These three layers were named in order from the synovial layer as "Internal fibrous layer (IFL)", "Intermediate fibrous layer (MFL)" and "External fibrous layer (EFL)". The external fibrous layer can normally be directly visualized by peeling off the muscles. The EFL consists of external fascia, tendons and their transitional regions, which compose the joint of the shoulder. IFL and MFL can only be observed under a low magnification microscope and are distinguishable on film preparations. The IFL, which is located immediately under the stratum synoviale, consists of fibrous bundles approximately 20 microns thick. The MFL, which is adjacent to the IFL, consists of 100-400 microns thick fibrous bundles. The IFL and the MFL have a differently fixed arrangement. The fibrous bundle of EFL is slightly thicker than that of IFL and the arrangement of the fibrous bundle is like that of supraspinatus m., infraspinatus m. and teres minor m. in the superior and posterior regions of the joint capsule. The local existence as well as the arrangement of the fibrous layer of these three different types is discussed from the standpoint of mechanical movement of the shoulder joint. PMID- 2216308 TI - The rhomboideus capitis in man--correctly named rare muscular variation. AB - This is the third original report on the rhomboideus capitis muscle in man, as far as the author is aware. In the earlier descriptions, the muscle was named as the occipito-scapularis and the rhomboideus-occipitalis or capitis. The muscle was situated on the left side of the neck as a muscular band attached cranially to the occipital bone and caudally to the scapula and was closely related to the splenius capitis and the levator scapulae. A revision of previous descriptions and a brief comparative note on the rhomboideus muscle is given. PMID- 2216307 TI - Effect of whole pituitary extract on the corpuscles of stannius in Notopterus notopterus (Pallas). AB - Administration of pituitary extract brings important change in the cells of the corpuscles of stannius. Two variety of cells are found in the corpuscles of stannius of control group, one with dense cytoplasm while the other possess non reactive cytoplasm. Under the influence of whole pituitary extract, there is an intense cell activity in corpuscles of stannius suggesting more synthesis of hypocalcemic factor. Other possible reasons like stimulation of interrenal, thereby activating corpuscles of stannius have also been discussed. The possible involvement of ACTH or cortisol and synergistic effect of prolactin in promotion of hypercalcemia have also been suggested. PMID- 2216309 TI - Allometric growth of the adrenal gland in Brazilian fetuses. AB - The growth of the adrenal gland was studied in 60 brazilian fetuses (12-37 weeks post-conception). The right adrenal gland was quantitatively evaluated; its weight, length and thickness were correlated to the fetal body weight, to the Crown-Pump length and to the gestational age by the allometric method (LogY = kLogX + LogB). The width was the only linear measure with positive allometry, and was the one which presented the greatest relative growth, while the thickness had the smallest one. The adrenal weight presented positive allometry relating to the Crown-Rump length (k = 2.32) and to the gestational age (k = 2.40). The importance of these knowledges in the precocious ultrasonographic diagnosis of congenital adrenal pathologies is discussed. PMID- 2216310 TI - The intermediate epithelium lining the nasopharynx of the Suncus murinus. AB - In the adult Suncus murinus, the rostral part of the nasopharynx is lined with the ciliated columnar epithelium continuing from the nasal cavity, while the laryngopharynx with the stratified squamous epithelium; i.e., the epithelium lining the caudal part of the nasopharynx forms the transitional zone between the ciliated columnar epithelium and the stratified squamous one. The epithelium shows gradations ranging from ciliated stratified low-columnar through stratified cuboidal to stratified squamous type. It is suggested that the epithelium is identical with the "intermediate epithelium (Nakano, 1986)". PMID- 2216311 TI - Two types of thyrotropes (TSH cells) in the adenohypophysis of the untreated mouse. AB - Employing immunohistochemical techniques with OsO4 single fixation, we identified mouse pituitary thyrotropes (TSH cells). The cells stained with TSH antiserum are angular or slender with a small nucleus. These cells contain small secretory granules (about 120-200 nm in diameter) and numbers of cored vesicles, either attached to the cell membranes or lying free in a relatively electron transparent cytoplasm. In the untreated male mouse, the TSH cell modifies its morphology according to the functional phase. The first form of TSH cells [Type I] is small. The endoplasmic reticulum and the Golgi apparatus are not prominent, and secretory granules are very few. In the second hypertrophied form [Type II], the endoplasmic reticulum is very prominent and occurs as a series of grossly dilated sacs of irregular shape. The Golgi apparatus is greatly enlarged and a large number of electron-dense secretory granules and cored vesicles are observed. Type II thyrotropes are rarely encountered in normal tissue. PMID- 2216312 TI - Gut formation after transection of the midgut loop in the chick embryo. AB - The primitive gut in vertebrates can be divided into the foregut, midgut, and hindgut. The midgut forms the midgut loop or the intestinal loop, which rotates as it develops the small and large intestines. We examined the effects of transection of the midgut loop on the subsequent development of the intestine in chick embryos by their out-of-the-shell incubation. The development of the embryo and the intestines out of the shell was nearly identical to that usual in-the shell incubation. The rotation of the midgut loop began in stage 27 (5 days of incubation) and was completed in stage 36 (10 days of incubation) after counterclockwise rotation through 180 degrees. In experimental groups, the midgut loop was transected immediately before or in the early stages of rotation (stages 27-33) proximally or distally to the apex of the loop. Transecting of the midgut loop caused little effects on its subsequent rotation regardless of the time or the site of transection although the secondary loop formation of intestine was poor in some cases. The stumps of the transected intestine were repaired and closed. After closure of the stumps, the proximal segment of the intestine was dilated in some cases. The secondary loop formation, or convolution of the intestine didn't occur in some dilated cases. PMID- 2216313 TI - Three dimensional arrangement of fibrocytes in the dermal papilla of the human sole skin. AB - The three dimensional arrangement of fibrocytes in the dermal papilla of the human sole skin was examined by the scanning and transmission electron microscopy after removal of the epidermis and collagenous fibers of the dermis by acidic maceration and enzymatic digestion with collagenase. Fibrocytes in the papillary layer were dendritic cells, consisting of bulky or flattened perikarya and numerous cytoplasmic processes of various size. The processes were anastomosed with those of neighboring cells forming a three-dimensional network. Fibrocytes around the blood capillaries were squamous and formed cellular sheaths, on which dendritic fibrocyte processes anchored. The outer surface of the papillae showed a fine villous appearance. It was composed of densely arranged tiny processes of fibrocytes, tops of which were almost at the same level. These processes may be sites for fibrillar attachment and play a role in dermal anchoring to the epidermis. In the reticular layer, fibrocytes were flattened, stellate cells which were anastomosed with neighboring cells and formed two-dimensional latticework. These cellular lattices were arranged in lamellae, oriented roughly parallel to the skin surface. Nerve bundles were often encountered in the labyrinthine space of the fibrocytic network. PMID- 2216314 TI - The posterior renal vein (new definition), together with its morphological significance. AB - A particular branch of the renal vein, which is detected behind the renal pelvis at the hilum at the rate of ca. 80%, and which is proposed as the posterior renal vein (PRV), may be remarked as morphologically significant. PRV may be divided into the typical and non-typical categories. But, in accordance with the bilateral asymmetry of the renal vein, PRV differs between the two sides. Thus on the right (82/270 = 30%), the first category of PRV directly joins the inferior vena cava (IVC) 1-3cm lower than the ordinary or anterior renal vein (ARV), and on the left (90/270 = 33%), it joins ARV after receiving the second lumbar vein in most of the examples. The other category of PRV (99/221 = 45%), which joins ARV near the hilum, is morphologically regarded to represent the former, which is degenerated to a certain extent. By considering the characteristics above and below the renal vein, the flowing level of PRV into IVC on the right will, above all, indicate the point of transition of the constituent portions of the developing IVC. In the meantime, in view of the assessment that the final portion of the left PRV represents IVC, PRV will afford a logical clue to understand the bilateral symmetry. The posterior veins as observed in the upper retroperitoneal cavity such as the suprarenal gland and diaphragm will constitute the posterior venous system related to PRV. PMID- 2216315 TI - Microvascular architecture of the hard palatine mucosa in the rabbit. AB - SEM studies on the microvascular architecture of the hard palatine mucosa, especially the transverse palatine plicae, and the morphological relations between the microvasculature and layers of the hard palate mucosa of the rabbit, were carried out by the acryl plastic injection method. The findings were compared with those obtained previously in the cat and Japanese monkey. Morphological differences and similarities between the papillae in the lamina propria and the capillary loops in the papillae were elucidated by SEM. A boneless area was found in the hard palate since the palatine fissures occupied a large area between the diastemata. The transverse palatine plicae numbered 14-16 symmetrically in the hard palate, and were more developed than those in the cat and Japanese monkey. In sagittal sections of the hard palate, the transverse palatine plicae were observed to be serrated, since they were located close to each other with small narrow interplical regions. The plical branches were usually derived from the major and minor hard palatine arteries, and formed the primary arterial network in the submucous layer of the hard palate. Twigs diverging from this network formed the second arterial plexus in the lamina propria, and furthermore, a subepithelial capillary network was formed immediately beneath the epithelium. From this network, capillary loops sprouted into papillae. Similarities were found between the papillae and capillary loops with locational differences. The descending crus of the capillary loop drained into the venous site of the subepithelial capillary network which flowed into the primary venous plexus in the lamina propria, which finally poured into the second venous plexus in the submucous layer. This plexus was termed the palatine venous plexus, and was especially well-developed in the area covering the palatine fissures. The capillary loops in the plica displayed characteristic features according to the portions within it and the interplical regions. PMID- 2216317 TI - Immunohistochemical study of intestinal lamina propria cells in the rat, with special reference to Ia antigen expression. AB - A previous study by Osogoe and Yanagi (1987a) has demonstrated that a large proportion of the lamina propria cells (LPC), mostly reticulum cells, in the core of the rat jejunal villi exhibit a strong labeling with [14C]adenine [( 14C]A). To obtain further information on such LPC, immunohistochemical detection of either Ia antigen or IgA on intestinal LPC was carried out in adult rats. It was found that almost all the LPC in the villous core of the small intestine express Ia antigen, and that in this area IgA-containing B cells also occur in unexpectedly large numbers. However, the number of Ia-positive non-B cells was greater than that of IgA-containing B cells which are also Ia-positive. Since the Ia-positive non-B cell population is composed mostly of reticulum cells, the above findings indicate that a large number of LPC, mostly reticulum cells, not only exhibit a strong labeling with [14C]A but also express Ia antigen. The biological significance of Ia antigen expression is discussed in relation to the proliferative activity of the cells. PMID- 2216316 TI - Postnatal transformation and location of mitoses in the epithelium lining the mouse vomeronasal organ. AB - The structure and the postnatal transformation of the epithelium lining the vomeronasal organ of the mouse was observed. The medial wall of the middle segment of the organ was lined with the sensory epithelium similar to the olfactory epithelium, and was not undergone any transformation in the postnatal life. The lateral wall of the middle segment and the entire lumen of the rostral segment were covered with the stratified cuboidal epithelium in the newborn mouse. The stratified cuboidal epithelium transformed into the ciliated columnar epithelium with advancing ages, excepting in the vomeronasal duct where the epithelium changed into the stratified squamous one. In the mouse aged between 4 and 10 days, mitotic figures were observed not only in the boundary between the sensory epithelium and the ciliated columnar one in the middle segment, but also in the rostral segment of which the entire lumen was covered with the ciliated columnar epithelium. PMID- 2216318 TI - The facial artery of the common marmoset (Callithrix jacchus). AB - The facial artery and its ramifications in 7 adult common marmosets (Callithrix jacchus) were studied by the plastic injection method. The findings obtained are discussed in comparison with those for other primates. In the submandibular region, the facial artery arose from the external carotid artery at the height of the atlas via the linguofacial trunk on 10 of the total of 14 sides examined and independently on the other 4 sides. This common trunk always gave rise to the superior thyroid artery. The facial artery passed anterolaterally between the styloglossus muscle and the intermediate tendon of the digastricus muscle, giving off the styloglossal and the submandibular glandular branches, and anteroinferiorly medial to the pterygoideus medialis muscle. In a position anterior to this muscle, the submental artery and masseteric branch were derived. The submental artery gave off the medial pterygoid, the digastric, the cutaneous, the sublingual glandular and the mylohyoid branches, and then continued up to the median line, where it terminated to supply the genioglossus muscle. In the facial region, the facial artery passed anterosuperiorly along the anterior margin of the masseter muscle on 12 sides and away from it forwards on 2 sides, giving off the premasseteric branch in one of these 2 sides. It gave rise to the cutaneous, the buccal and the buccinator branches, the inferior labial artery and the communicating branch with the zygomatic artery. It terminated to divide into the superior labial and the naris lateral arteries, although the latter was lacking on 4 sides. The inferior labial artery gave off the mandibular marginal, the inferior labial marginal and the inferior labial glandular branches and terminated to anastomose with the mental artery. The superior labial artery divided into the superficial and deep branches, each of which continued as a nasal septal branch. The facial artery of the common marmoset usually ascended along the anterior margin of the masseter muscle and did not reach the medial angle of the eye. PMID- 2216319 TI - Support for the recovering nurse within the employing agency. PMID- 2216320 TI - 'If caring were enough, anyone could be a nurse'. PMID- 2216321 TI - Annual meeting program of the American Academy of Optometry. Nashville, Tennessee, December 6-10, 1990. Proceedings. PMID- 2216322 TI - The change in the neutral point of dichromats with change in the angle of incidence of monochromatic light on the retina. AB - The hypothesis was tested that the change in the perceived color of monochromatic light with change in its angle of incidence on the retina can be accounted for completely by prereceptor factors alone. This was evaluated by measuring the change in the match of a monochromatic light to a fixed (and normally incident) white light as the monochromatic beam changed its traverse through the eye from chief ray to "off-axis" retina incidence at the margin of the exit pupil. Two protanopes and four deuteranopes were tested. In each case, the wavelength of the chief ray at the match was consistently, reliably, and (statistically) significantly larger than that of the match with the "off-axis" beam. The result cannot be accounted for by prereceptor factors alone. PMID- 2216323 TI - Directionalization of visual targets during involuntary eye movement. AB - Perceived visual direction with respect to one's self (egocentric direction) depends upon the retinal location of a target's image (its oculocentric direction) and concurrent information about the position of the eyes in the head. Information about eye position is presumably obtained from efference copy signals. However, in order to explain illusory target motion that can occur during reflexive eye movements (e.g., post-rotary nystagmus), these signals have been suggested to accompany only voluntary oculomotor responses. In the experiment reported here, manual pointing was used to assess the perceived direction of targets flashed during optokinetic afternystagmus, an involuntary movement of the eyes that occurs in darkness following optokinetic stimulation. Egocentric directionalization was essentially veridical, indicating that accurate eye position information is available during optokinetic afternystagmus. A model is proposed that accounts for illusory target motion during involuntary oculomotor responses by the cancellation of efference copy information about these eye movements with signals of oppositely directed head motion. PMID- 2216324 TI - Measuring visual acuity in children using preferential looking and sine wave cards. AB - Preferential looking using square waves is commonly used to measure visual acuity of infants. Since sine-wave gratings have the advantage of presenting only a single spatial frequency, we completed a study to develop and validate a set of acuity cards using sine waves. The subjects were 83 children (mean age = 41.5 months, range = 3 to 69 months). The sine-wave cards were compared with Teller cards. Identical visual acuity was determined in 83% of the cases. Wilcoxon non parametric analysis provided no evidence to reject the null hypothesis of equal visual acuities between the two methods. We conclude that sine-wave cards may be used to measure the preferential looking acuity of children. PMID- 2216325 TI - Saturation and purity of near-threshold spectral increments on achromatic backgrounds. AB - Vector models of color vision predict that the chromatic saturation of near threshold incremental stimuli should grow with increasing achromatic adaptation. In contrast, colorimetric models predict that saturation should decrease with increasing adaptation in correspondence with excitation purity. An experimental test disagrees with both predictions, but is consistent with a two-process model of chromatic adaptation and contrast. Foveal monochromatic test stimuli 0.6 log unit above threshold were superposed on achromatic backgrounds with retinal illuminances of up to 5.3 log Td. Saturation and purity both decreased as background illuminance increased up to 2 log Td, but the saturation decrease was relatively small. As background illuminance increased above 2 log Td, purity remained nearly constant and saturation often increased, making the overall saturation function U-shaped. Thus, a purity of 0.1 at high background illuminance could sometimes elicit a higher saturation estimate than a purity of 0.9 at low background illuminance. PMID- 2216327 TI - Is the relation between keratometric astigmatism and refractive astigmatism linear? AB - Javal's rule, which states that the total astigmatism of the eye--or refractive astigmatism--is equal to 1.25 (keratometric astigmatism) - 0.50 x 90, implies a linear relation between the two entities. Data published by Grosvenor, Quintero, and Perrigin (Am J Optom Physiol Opt 1988;65:292-7) show that for eyes having no more than 2.50 D of keratometric astigmatism, the slope of the regression line for refractive astigmatism plotted against keratometric astigmatism is less than 1.00, rather than the 1.25 required by Javal's rule. When data compiled for eyes having greater amounts of keratometric astigmatism are plotted in the same manner, the slope of the regression line is greater than 1.00, suggesting that the relation between keratometric and refractive astigmatism may be non-linear. However when data for these highly astigmatic eyes are plotted in combination with data published by Grosvenor, Quintero, and Perrigin, they are adequately characterized by a straight-line relation. PMID- 2216326 TI - Effect of bleaching on the width and index of refraction of goldfish rod and cone outer segment fragments. AB - Data on goldfish rod and cone fragments were obtained before and after a strong bleach by using a Zeiss Jamin-Lebedeff infrared interference microscope and computer image processing techniques. The receptor fragments were fractured in the inner segment and were immersed in goldfish aqueous humor medium. On bleaching we found that: (1) there is a small increase in rod diameter. This effect is of the same magnitude reported earlier in Rana pipiens outer segments (Vision Res 1973; 13:171). (2) There is an inferred decrease in rod refractive index. (3) There is a decrease in cone width. (4) There is a slight increase in inferred cone refractive index. These data are presented. PMID- 2216328 TI - Physiological pseudomyopia. AB - Objective refraction through plus fogging lenses and base-in prisms revealed that normally accommodation is not completely relaxed when the stimulus to accommodation is zero. The myopic shift in the refractive error due to this focus error of accommodation was defined as physiological pseudomyopia. Two previously established features of accommodation are responsible for this behavior: (1) accommodation acts as a proportional control system for steady-state responses; and (2) the rest focus of accommodation is nonzero. It is proposed that the hyperopic shift in refraction observed in cycloplegia is the result of elimination of physiological pseudomyopia. PMID- 2216329 TI - Image evaluation of ophthalmic devices. AB - Methods used in the ophthalmic industry to evaluate the optical image quality of correcting lenses have remained the same over many years. This is especially true for single-vision ophthalmic lenses. With the development of new optical designs and materials for correcting refractive errors and presbyopia, new procedures for evaluating lens performance are being explored. One such method is the measurement of the modulation transfer function. Over the last 2 years, we have been measuring modulation transfer functions on a variety of single-vision and bifocal contact lenses, progressive addition spectacle lenses, holographic diffractive lenses, and intraocular lenses. In this article, the modulation transfer function procedure and its application and results from one study on safety goggles will be presented and discussed. PMID- 2216330 TI - The Video Display Terminal Eye Clinic: clinical report. AB - The Video Display Terminal Eye Clinic was designed to relieve the symptoms of video display terminal users by diagnosing and treating visual problems and by analyzing the patients' work station environment through an in-office simulation and making suggestions for improvements. The Clinic was open to the public and patients were therefore self-selected. The symptoms, diagnoses, and treatments were compiled retrospectively and reported for 153 patients. Vision problems were diagnosed in most patients. The most frequent diagnoses included: presbyopia, improper spectacle design for presbyopia, accomodative deficiencies, esophoria, exophoria, and hyperopia. The results suggest that proper visual care and work station arrangement can improve comfort. PMID- 2216331 TI - Detection of disparity motion by the human observer. AB - A single-line stimulus in a context-free visual environment presented for 250 msec needs to move with a disparity velocity of 25 to 45 min of arc/s before the direction of depth motion can be correctly identified. Presence of a pair of flanking line stimuli improves this value severalfold, but even then the threshold is 18 to 28 times higher than for the detection of a static disparity difference. PMID- 2216332 TI - Variables related to the rate of childhood myopia progression. AB - This study was undertaken to examine the relations between the rate of childhood myopia progression and variables available in patient records. Data were obtained from four private optometry practices and two university-based longitudinal studies. Subjects were myopes with a minimum number of refractions between the ages of 6 and 15 years. Spectacle prescription types included single-vision lenses with exact distance correction or slight undercorrection, bifocal lenses, and single-vision lenses with overcorrection. Rates of progression were determined by linear regression. Three analyses were conducted: (1) for all patients, analysis of variance of rate as a function of heterophoria through the habitual nearpoint correction, an index of the amount of myopia at the initial examination age, sex, and clinical location; (2) for patients with esophoria through the distance ametropia correction, analysis of variance of rate as a function of correction type (full correction or slight undercorrection vs. bifocals), amount of myopia at the initial examination age, sex, and location; and (3) for patients with orthophoria or exophoria with ametropia correction, analysis of variance of rate as a function of correction type, amount of myopia at the initial examination age, sex, and location. The index of amount of myopia at the initial examination age was a significant variable, as was location. Patients with nearpoint esophoria through their habitual nearpoint correction had greater rates than patients with nearpoint orthophoria or exophoria with the habitual correction. For patients with nearpoint esophoria through the distance refractive correction, rates were less with bifocals than with full correction or slight undercorrection. PMID- 2216333 TI - Rates of childhood myopia progression with bifocals as a function of nearpoint phoria: consistency of three studies. AB - Three studies on the effect of bifocal lenses on childhood myopia progression are discussed and re-analyzed. In all three, the rates of progression were less with bifocals than with single-vision lenses in esophoria. Rates with the two types of correction were similar in patients who had nearpoint orthophoria or exophoria. PMID- 2216334 TI - Influence of rigid contact lens overall and optic zone diameters on tear pump efficiency. AB - To determine the effects of contact lens overall diameter on tear pump efficiency, oxygen uptake rates were measured for the open-eye condition and following steady-state periods of static (without blinking) and dynamic (with blinking once every 5 s) contact lens wear of oxygen-impermeable (polymethylmethacrylate) lenses of 5 overall diameters (8.2, 8.5, 8.8, 9.1, and 9.4 mm). The optic zone diameters were 1.4 mm smaller than the overall diameters in each case, while all other parameters remained constant. Differences in corneal oxygen demand following the static and dynamic conditions are a quantitative index of the tear pump efficiency for each lens size on the same cornea, and the differences were found to increase with reduction in lens overall diameter. This indicated that a more efficient tear pump was associated with small diameter designs. In addition, subjects with large palpebral aperture size, relative to lens overall diameter, were found to demonstrate better tear exchange. PMID- 2216335 TI - Reactivation of ocular toxoplasmosis. PMID- 2216337 TI - Rose bengal staining before and after anesthetic. PMID- 2216336 TI - High and low contrast acuity. PMID- 2216339 TI - Ophthalmology sourcebook & reference guide 1990. PMID- 2216338 TI - Historical roots of 20/20 as a (wrong) standard value of normal visual acuity. PMID- 2216340 TI - Evaluation of the efficacy of anthelmintics against parafilariosis in cattle. AB - Parafilariosis was first described in South Africa in 1964, thereafter being discovered at numerous localities in the country. When it became obvious that Parafilaria bovicola, for which no treatment was known, caused considerable economic losses, trials involving a series of compounds were conducted to identify candidate remedies. This paper describes an anthelmintic test for evaluating the efficacy of compounds for registration for field use. Recovery of Parafilaria worms is impractical for anthelmintic testing, and consequently the lesion sizes of treated and control groups of cattle are compared statistically, using appropriate statistical tests. The seasonal incidence of mature worm infection in cattle in South Africa is such that trials should commence after June and be completed before the end of January, allowing a lapse of 70 days between treatment and slaughter for resolution of the lesions. The presently available parafilaricidal compounds while of value for treating slaughter stock, when used alone will probably not be effective for control of infection in the field. PMID- 2216341 TI - Pyridoxine (a vitamin B6) and its derivative pyridoxal as treatment for Albizia versicolor poisoning in guinea-pigs. AB - In the course of three experiments it was established that all the toxic effects of a lethal dose of Albizia versicolor pods (greater than 4.5 g/kg) in guinea pigs could be countered by concurrent subcutaneous injection of pyridoxine (10 mg/kg). This treatment was also successful once severe symptoms had set in. Pyridoxal, on the other hand, was found to be ineffective as a therapeutic agent. The fact that pyridoxal does not counter the action of the toxin indicates an atypical site of action by the toxin as regards the normal pathways which require vitamin B6 as a co-factor. PMID- 2216342 TI - Fitting the Gompertz function to dose-response data of larval tick populations. AB - Samples of 6, 1st generation larval populations of Boophilus decoloratus, originating from field collected females, were subjected to increasing doses of the organophosphate acaricide, Dioxathion. The dose-response relationship for 3 populations showed random heterogeneity, while systematic deviations from the linear probit lines were observed for the other 3 populations. Logistic and Gompertz regressions were also fitted for all 6 populations. Probit regressions fitted best for 2 populations exhibiting heterogeneous responses. The logistic regression fitted best for 1 population with heterogeneous responses and 1 population with systematic deviating responses. The Gompertz regression fitted best for the 2 remaining populations exhibiting systematic deviating responses. The Gompertz function may be useful in describing the dose-response relationship obtained for certain acaricidal toxicity tests. PMID- 2216343 TI - A field strain of Trichostrongylus colubriformis resistant to levamisole and morantel in South Africa. AB - A strain of Trichostrongylus colubriformis from Nottingham Road, in Natal, was found to be solidly resistant to levamisole and morantel at the recommended dose levels. Untreated control sheep in fact harboured fewer worms at slaughter than either of the 2 treated groups. In contrast, the benzimidazoles and ivermectin were more than 99.9% effective against this worm strain. The possible implications of escalating resistance to anthelmintics in the gastrointestinal nematodes of sheep are discussed. PMID- 2216344 TI - On sampling tick populations: the problem of overdispersion. AB - Data collected on both free-living and parasitic tick populations are likely to be overdispersed. The use of means from few replicate samples of overdispersed data as quantitative estimators of tick population density is in turn likely to lead to inaccurate interpretations which may be scientifically misleading. In this paper ways of estimating overdispersion are listed and suggestions for the use of correct statistical tests for handling overdispersed data are given. PMID- 2216345 TI - The use of sensitivity discs in the identification of Campylobacter species. AB - Filter paper discs were impregnated with a solution containing 20 mg of triphenyltetrazolium chloride per millilitre, and used in the typing of catalase positive Campylobacter species. Also used were filter paper discs impregnated with cephalothin at 30 micrograms/ml, 60 micrograms/ml and 3 mg/ml and nalidixic acid at the same concentrations, as well as commercially available discs containing 30 micrograms of, respectively, cephalothin and nalidixic acid. Results obtained proved the technique to be reliable and easier to interpret than previously used methods, and laboratory prepared filter paper discs compared favourably with commercial discs. PMID- 2216346 TI - Effects of microclimatic variables on the availability and movement of third stage larvae of Ostertagia ostertagi on herbage. AB - Assessments were made of the influence of several microclimatic variables on the availability of third-stage larvae of Ostertagia ostertagi, on pasture herbage. Variables most closely related to recovery of larvae from the lower herbage samples were: maximum air, mat and dung temperatures. Recovery of larvae from the upper portion of the herbage was closely correlated with dung temperature, sampling-time air temperature and maximum air temperature. Bearing in mind that the moisture threshold was maintained throughout the trial the results of this study suggest that under field conditions, larval movement of third-stage O. ostertagi larvae on herbage is regulated primarily by temperature. PMID- 2216347 TI - Host cellular components adhering to the tegument of schistosomes from cattle, buffalo, hippopotamus and lechwe. AB - The teguments of adult Schistosoma mattheei from cattle and buffalo, S. hippopotami from hippopotamus and S. margrebowiei from lechwe were examined by means of scanning electron microscopy for cells possibly engaged in immunological action. Leukocytes were observed on the teguments of the schistosomes from all 4 host species. Although certain of these cells seemed to be fused to the surface membrane of the worms, they did not display pseudopodia. The tegument of certain schistosomes from buffalo exhibited cells the size of platelets with dendritic structures connected to the tegument of the parasite. The results seem to indicate that, as with laboratory hosts, naturally infected domestic and wild hosts are unable to mount an effective cellular response against the tegument of live adult shistosomes. The possible role of platelets in immunology against schistosomes is mentioned. PMID- 2216348 TI - Feeding habits and flight range of blow-flies (Chrysomyia spp.) in relation to anthrax transmission in the Kruger National Park, South Africa. AB - Carrion-frequenting blow-flies (Chrysomyia albiceps and C. marginalis) were allowed 4 days of feeding on 32P-orthophosphate-labelled blood or an impala carcass (Aepyceros melampus) in the northern Kruger National Park, South Africa. The dispersal and density of fly faecal and discard droplets were then established using a Geiger-Counter, indicating that most droplets occurred between a height of 1 and 3 m on nearby leaves and twigs. This coincides with the preferred feeding height of kudu (Tragelaphus strepsiceros). During a previous anthrax epizootic kudu comprised 73.15% of a total medium to large mammal mortality figure of 1054. Further analysis of mortality shows browsers to have been most severely affected, and it is suggested that this is correlated with feeding habits of these animals. Trapping also yielded radioactively labelled C. albiceps up to 32.5 km and C. marginalis up to 25 km from the isotope source. PMID- 2216349 TI - The isolation and serology of Brucella melitensis in a flock of goats in central RSA. AB - Brucella melitensis biotype 1 was isolated in pure culture from the lungs, liver, spleen, kidney, stomach contents, abomasum and brain of an aborted caprine (Boer goat) foetus in the district of Cullinan near Pretoria. The 18 does and 1 ram in the flock of Boer goates were examined serologically by means of the complement fixation (CF) test, using Brucella abortus antigen. Six weeks later they were examined again, using B. abortus as well as B. melitensis biotype 1 antigens. No significant differences were found between the 2 CF tests using B. abortus antigen, or between the results obtained by using the B. abortus and B. melitensis antigens. Twelve goats, showing CF antibody titres, were slaughtered and examined bacteriologically. No relationship was found between the serological and bacteriological results. PMID- 2216350 TI - The modified superior based pharyngeal flap. Part I. Surgical technique. AB - The superior based pharyngeal flap operation for the correction of velopharyngeal incompetence is perhaps the most commonly employed operation used today in a majority of cleft palate centers. However, inconsistent results with this operation are commonplace. This is believed by most to be due to poor control of the lateral portals. Herein is a report of our approach to improve lateral portal control. PMID- 2216351 TI - The modified superior based pharyngeal flap technique. Part II. An anatomic study. AB - There is little in the literature on the topographic and/or applied surgical anatomy related to superior based pharyngeal flap surgery. Herein we report on the applied surgical anatomy of pharyngeal flap surgery, especially as it applies to critical anatomic relationships to vessels, muscles, and nerves. PMID- 2216352 TI - The modified superior based pharyngeal flap. Part III. A retrospective study. AB - A retrospective study of 31 patients who had diagnosed velopharyngeal incompetence and were surgically managed with the modified superior based pharyngeal flap was completed. The following were analyzed: age at time of operation, gender, physical status, diagnostic protocol, length of operation (length of total surgery) and length of superior based pharyngeal flap, length of postoperative hospital stay, length of total hospital stay, length of follow-up, speech results, complications, patient care, and medication. The result showed that the optimal timing for correction of velopharyngeal incompetence was between 3 and 6 years of age. The mean length of total hospital stay was 2.7 days, postoperative complications were minimal, and speech results were generally good. PMID- 2216353 TI - Capillary hemangioma of the maxilla. A report of two cases in which angiography and embolization were used. AB - This article presents two clinical cases of capillary hemangiomas of the maxilla. Such lesions are rare, as demonstrated by the review of the literature included in this article. The presentation, differential diagnosis, histopathology, management, and follow-up for each case are discussed. Our rationale for approaching these types of lesions, as well as our opinion that microembolization should be considered as a first line approach to treatment, is presented. PMID- 2216354 TI - Oral squamous cell carcinoma arising in a patient with long-standing lichen planus. A case report. AB - The risk of malignant transformation of oral lichen planus remains a controversial point. Many previous reports have been discounted on the basis of inadequate information or lack of histologic confirmation of lichen planus. We report a well-documented case of long-standing cutaneous and oral lichen planus in which squamous cell carcinoma of the dorsal portion of the tongue occurred. There is an apparent difference in the sites of oral carcinomas in patients with lichen planus compared with the general population. This suggests that lichen planus increases the risk of oral cancer in affected sites. PMID- 2216355 TI - Premature alveolar bone loss in Erdheim-Chester disease. AB - Erdheim-Chester disease is a rare histiocytosis also known as lipoid granulomatosis. Oral findings have not been reported previously to our knowledge. This case report documents evidence of oral sequelae of Erdheim-Chester disease. A patient whose course was followed for 10 years at the National Institutes of Health had premature alveolar bone resorption. He underwent full-mouth extraction at age 29 years because of severe periodontitis. Histopathologic evidence of Erdheim-Chester disease was demonstrated in the periodontal soft tissues. In the ensuring years, accelerated resorption of the residual ridges precluded the use of conventional dentures. We recommend early preventive dental management for patients with Erdheim-Chester disease. PMID- 2216356 TI - Safe storage times for sterile dental packs. AB - Safe storage times were evaluated for three sterile packaging materials that are commonly used in dentistry. No significant differences were found among packaging materials. Only three packs of 300 produced positive cultures during the 1-year test period. There were no time-related trends. The contamination levels found were within the range that has been reported to occur as a result of inadvertent contamination during unpackaging and transfer of sterile instruments. The findings of this study support the proposal that contamination is event related, not time related; that is, sterile instrument packs remain sterile for at least 1 year unless a specific event causes contamination. PMID- 2216357 TI - Dental abnormalities associated with familial expansile osteolysis: a clinical and radiographic study. AB - Familial expansile osteolysis is a rare and possibly unique form of hereditary bone dysplasia with dental manifestations that has affected 42 members of a Northern Ireland family for five generations. Twenty-seven family members, aged 3 to 60 years, were examined clinically and radiographically, and it was found that cervical and/or apical root resorption is an early manifestation of the dysplasia. Of the 20 family members with skeletal manifestations of familial expansile osteolysis, 16 showed root resorption. Root resorption may therefore be a good prognosticator for later bone involvement. PMID- 2216358 TI - Differences between florid osseous dysplasia and chronic diffuse sclerosing osteomyelitis. AB - Florid osseous dysplasia (FOD) is confused in the literature with chronic diffuse sclerosing osteomyelitis. Two cases of each condition are presented to demonstrate the differences between them. In FOD, there are multiple lobulated sclerotic masses in several quadrants of the jaws, usually in black females. In some cases, the sclerotic masses are exposed to the oral cavity, resulting in a secondary osteomyelitis. Periapical cemental dysplasia is often found in association with FOD. Chronic diffuse sclerosing osteomyelitis is a primary inflammatory condition of the mandible. Patients have cyclic episodes of unilateral pain and swelling. The affected region of the mandible exhibits a diffuse opacity with poorly defined borders. Although women are affected more often than men, black persons are not particularly susceptible. PMID- 2216360 TI - Photoelastic stress comparison of warm (Endotec) versus cold lateral condensation techniques. AB - Stress generated during gutta-percha obturation of root canals can create microcracks and ultimately lead to failure. A new thermosoftening device, the Endotec, which develops a warm lateral condensation technique, was tested against the traditional lateral condensation procedure. The results indicated that the warm lateral condensation technique created less stress during obturation than did cold lateral condensation. PMID- 2216359 TI - Contiguous enlarged dental follicles with histologic features resembling the WHO type of odontogenic fibroma. AB - Defective odontogenesis and/or retarded eruption of teeth can be associated with histologic features akin to odontogenic fibroma in the dental follicles. Unerupted mandibular premolar and molar teeth of a 24-year-old man were surgically exposed, yet the teeth failed to erupt. About a year and a half later, radiographs indicated further enlargement of the follicle of the premolar, and both teeth were subsequently surgically removed. Histologically, the follicles were composed of mature collagenous tissue among which epithelial islands and numerous clusters of calcified bodies were present. Indirect immunofluorescence showed positive staining for type I and type III collagen, which exhibited a sparse distribution, but not for the aminoterminal propeptide of type III procollagen. The hamartomatous nature of the lesions is discussed with emphasis on their histologic resemblance to the WHO type of odontogenic fibroma. PMID- 2216361 TI - Effectiveness of ultrasonic files in the disruption of root canal bacteria. AB - The physical mechanisms of ultrasound, namely cavitation and acoustic streaming, generated by the Enac-Osada ultrasonic unit were investigated for effectiveness in disrupting Streptococcus mitis. In addition, the bactericidal effect of ultrasound in the presence of 2.5% sodium hypochlorite was examined. Bacterial suspensions were irradiated directly with ultrasound in simulated root canals, and the viability of bacteria was examined after growth on a blood agar medium under anaerobic conditions at 37 degrees C for 5 days. The results indicated that ultrasound per se failed to disrupt bacteria but resulted in increases in the viable counts; the former was considered to be because of the lack of cavitation and the latter because of the dispersal effects of acoustic streaming. The 2.5% sodium hypochlorite solution demonstrated powerful bactericidal activity. PMID- 2216362 TI - A dentist's dilemma: nonsurgical endodontic therapy or periapical surgery for teeth with apparent pulpal pathosis and an associated periapical radiolucent lesion. AB - First presented is a brief review of nonsurgical versus surgical treatment of radicular cysts. This is followed by a consideration of the use of radiographs for differential diagnosis of periapical radiolucent lesions. Some of the nonendodontic local and systemic lesions that can occur periapically are then presented. Next examined are the fallibilities of pulp vitality testing methods. The need for histopathologic examination of periapical lesions is the subject of the next discussion. The dentist's dilemma is then examined: should teeth with apparent pulpal pathosis and an associated periapical radiolucent lesion have routine surgical treatment including biopsy or should they be treated nonsurgically and have periodic follow-ups? A possible resolution of this dilemma is the final consideration. PMID- 2216363 TI - A new method of tooth replantation and autotransplantation: aluminum oxide ceramic for extraoral retrograde root filling. AB - After an initial clinical test phase, the new method of replantation and transplantation with the use of aluminum oxide ceramic for retrograde root filling may be viewed as possible differential indications to other methods, even to apicectomy in the molar region. Twenty-three of the twenty-five replantations and eight of the nine transplantations may be regarded as having been successful. Contraindications are cases of wide apical foramina and oval or octagonal root canal cross sections. PMID- 2216364 TI - A clarification on endodontic flare-ups. AB - In an article on endodontic flare-ups by Robert J. Matusow, our research and publications are discussed. Since we found what we consider to be distortions and misinterpretations of our work, it was decided to clarify the apparent discrepancies found in Matusow's article. PMID- 2216365 TI - The radiologic morphology of asymptomatic temporomandibular joints. AB - A high frequency of remodeling changes was demonstrated radiographically in a series of 200 female patients with asymptomatic temporomandibular joints. Fewer than 10% of joints were completely radiologically "normal". Generally, there was an increasing incidence of changes with increasing age and for edentulous patients, but these relationships were by no means direct or mutually exclusive. PMID- 2216366 TI - The radiologic morphology of painful temporomandibular joints. AB - A high frequency of remodeling changes was demonstrated radiographically in a series of patients having pain in the temporomandibular joint region. Radiologic morphologic differences between painful and asymptomatic temporomandibular joints were in frequency rather than type. Caution should be taken not to overestimate the significance of radiologic abnormality in patients with pain in the temporomandibular joint region. PMID- 2216367 TI - Unexpected dental caries. PMID- 2216368 TI - Calcified blood vessel. PMID- 2216369 TI - Devastated root. PMID- 2216370 TI - Peg-shaped mandibular second premolar. PMID- 2216371 TI - Silicone rubber fossa implant removal via partial arthrotomy followed by arthroscopic examination of the internal surface of the fibrous capsule. AB - Thirteen temporomandibular joints were examined arthroscopically for evaluation for fibrous encapsulation of silicone elastomer disk replacement implants. Partial arthrotomies were performed with removal of silicone rubber implants, followed by arthroscopic examination of the internal surfaces of the fibrous capsule as a pseudodisk and to verify the continuity of the fibrous barrier between the condyle and the fossa. PMID- 2216372 TI - A comparative study of temporomandibular symptoms following mandibular advancement by bilateral sagittal split osteotomies: rigid versus nonrigid fixation. AB - Rigid fixation to attach proximal and distal segments during bony healing of osteotomy sites has become increasingly popular. The effects of rigid fixation on the temporomandibular joints have been questioned. The purpose of this study was to evaluate the effects of rigid fixation after bilateral sagittal split osteotomies on temporomandibular dysfunction symptoms. Forty patients who had mandibular advancement surgery were evaluated for temporomandibular joint dysfunction. Twenty had received rigid fixation, and twenty had received nonrigid fixation. It was determined that there was no statistically significant difference in temporomandibular signs or symptoms between patients who were treated with rigid internal fixation for bilateral sagittal split osteotomies for mandibular advancement and those patients who were treated with nonrigid wire fixation. PMID- 2216373 TI - A retrospective evaluation of 301 TMJ Proplast-Teflon implants. AB - A retrospective review of 301 meniscectomies with Proplast-Teflon implants was performed. Factors such as interincisal opening, occlusion, joint sounds, joint degeneration, and patient satisfaction were examined. The overall surgical success rate was 88.7%, with an average follow-up period of 33 months. Although many patients demonstrated significant condylar degeneration at 1-year follow-up, such change did not necessarily result in symptomatology or joint dysfunction. Only 10% of implants resulted in removal. Surgical and postoperative procedures are contrasted with those of other clinicians experiencing lower success rates. PMID- 2216374 TI - Arthroscopic and histologic evidence of chondromalacia in the temporomandibular joint. PMID- 2216375 TI - A histologic evaluation of the accuracy of TMJ diagnostic arthroscopy. AB - Sixty-seven temporomandibular joints with internal derangement were examined with arthroscopy, and synovial biopsies were taken for histologic evaluation. Histologically, in 10 cases, the synovium appeared to be normal in appearance, 24 cases had moderate to severe synovitis, 11 cases showed hyperplastic synovitis, 13 cases showed synovial fibrosis, and foreign body granuloma was found in 9 cases. Correlation between arthroscopic observation and histologic findings disclosed an 89.1% specificity and 100% sensitivity. PMID- 2216376 TI - A unique indexing splint for use in combined Le Fort and nasal injuries to avoid tracheostomy. AB - Midface fractures with associated displaced and/or comminuted nasal fractures can require tracheostomy for a general anesthetic airway if these fractures are to be reduced simultaneously. We describe a unique indexing splint that allows oral intubation yet also allows simultaneous reduction of midface and nasal fractures under one anesthetic. Furthermore, tracheostomy with its potential complications is avoided. The case report illustrates the technique, and alternative treatments for these injuries are discussed. PMID- 2216377 TI - Temporomandibular joint dysfunction and selected health parameters in the elderly. AB - Little research has focused on temporomandibular joint dysfunction (TMJD) in the elderly. The present study describes relationships between TMJD and selected health parameters in a population of 75- to 94-year-old Roman Catholic sisters (nuns). Mental, physical, and oral assessments made on 117 sisters identified 26 with TMJD. Among all sisters, TMJD was not associated with age, education, mental impairments, hand coordination, handgrip strength, mobility, or use of walking aids. In 75- to 84-year-old sisters, TMJD was positively associated with self reported arthritis (p = 0.12), edentulism (p = 0.09), and the presence of complete dentures (p = 0.05), and negatively associated with the number of teeth present (p = 0.05), especially the posterior teeth. These associations were weaker in 85- to 94-year-old sisters. This study suggests that TMJD is associated with the presence of complete dentures and a low number of teeth, especially the posterior teeth. PMID- 2216378 TI - Diffuse sclerosing osteomyelitis of the mandible: a new concept of its etiology. AB - Diffuse sclerosing osteomyelitis of the mandible is a disease of unknown etiology. The clinical and radiographic findings suggest an infectious origin, but bacteriologic and histologic findings do not support this concept. Analysis of clinical symptoms, localization of the condition, and posttreatment findings in a group of 27 patients suggest a chronic tendoperiostitis due to muscular overuse as an etiologic factor in diffuse sclerosing osteomyelitis of the mandible. This hypothesis was supported by the initial results of muscle relaxation treatment in 13 of these patients. PMID- 2216379 TI - Patient compliance--a factor in facial trauma repair. AB - The clinical records of 25 consecutive patients who were treated for facial trauma were reviewed and analyzed to ascertain what effect patient cooperation had on the outcome of facial fracture repair. The study was designed to establish the incidence of complications and to discover what factors contributed to untoward sequela in such patients. Overall, 15 patients (60%) were noncompliant in one or more aspects of their care. Six patients (24%) had significant postoperative complications associated with their facial injuries. Four of these patients were not fully cooperative. PMID- 2216380 TI - Apparent regeneration of the mandibular canal in a free bone graft. PMID- 2216381 TI - More unusual pigmentations of the gingiva. AB - Three unusual types of oral pigmentation are presented. The first is a brown orange pigmentation caused by the habit of using the bark of Juglans regia for teeth cleaning. The second is a bright yellow pigmentation associated with the habit of chewing the seeds of Cola nitida. The third is a generalized mousy brown pigmentation related to the habit of chewing the leaves of Catha edulis. The purpose of this article is to describe the nature of these pigmentations and to present their clinical and histologic features. PMID- 2216382 TI - Adult linear immunoglobulin A disease manifesting as desquamative gingivitis. AB - Desquamative gingivitis is a manifestation of various dermatoses, particularly lichen planus and mucous membrane pemphigoid. A rare example of adult linear immunoglobulin A disease manifesting as desquamative gingivitis is presented. Although the initial clinical features were typical of desquamative gingivitis, the persistence of ulceration after dental extractions was unusual, and the management of the oral lesions proved difficult. The clinical, immunopathologic, and therapeutic aspects of linear immunoglobulin A dermatoses are reviewed. PMID- 2216383 TI - Peripheral giant cell granuloma: evidence for osteoclastic differentiation. AB - Nine cases of peripheral giant cell granuloma of the oral cavity have been immunohistochemically analyzed to assess the nature of the giant cells. Giant cells were unreactive when tested with antibodies recognizing myelomonocytic and macrophage markers (lysozyme, MAC 387, HAM 56) but showed strong immunoreactivity with MB1, an antibody reactive with osteoclasts. It is concluded that giant cells characterizing giant cell granuloma exhibit a phenotype distinct from other giant cells found in sites of chronic inflammation and may be true osteoclasts. PMID- 2216384 TI - Progressive osseous destruction as a complication of HIV-periodontitis. AB - A pathologic condition is described, characterized by rampant necrosis of gingival mucosa, periodontium, and related osseous structures associated with systemic infection with the human immunodeficiency virus (HIV). It is believed that this condition is an extension beyond the normal clinical course of HIV periodontitis (HIV-P) and manifests itself in three progressive stages: (1) HIV associated gingivitis, (2) HIV-P, and (3) an extension of HIV-P to osseous necrosis. Two cases of osseous destruction attending HIV-P are reported, one of which led to initial diagnosis of HIV infection. They represent the final stage of disease progression with localized necrosis of gingiva, periodontium, and alveolar bone. PMID- 2216385 TI - Tyrosine-rich crystalloids in a polymorphous low-grade adenocarcinoma. AB - A polymorphous low-grade adenocarcinoma with tyrosine-rich crystalloid deposits is reported. The literature is reviewed, and diagnostic and histogenetic implications of this finding are discussed. PMID- 2216386 TI - Periapical lesions of mandibular bone: difficulties in early diagnostics. AB - It is often difficult to establish a correct diagnosis on the basis of initial clinical and roentgenologic symptoms in mandibular bone disease. In this paper these problems are discussed, and some suggestions are made to overcome them. The discussion is based on cases of osteogenic sarcoma, histiocytic lymphoma, and chronic osteomyelitis. The patients were a boy and two middle-aged women, all of them with primary clinical symptoms of pain and swelling, diffuse roentgenologic changes in mandibular bone, uncertain response to treatment, and an unusual progress of the disease. PMID- 2216387 TI - Clinical factors associated with ledged canals in maxillary and mandibular molars. AB - No clinical studies have been done to explore the relationship of ledging to the clinical practice of endodontics. The purpose of this study was to examine 171 cases completed by third-year dental students and to identify variables that were associated with ledging. A total of 336 canals were examined and tooth number, canal location, working length, the master apical file size, and root canal curvature were recorded. Of 336 canals, 46% were found to have been ledged. Analysis of variance revealed that No. 15 had a significantly higher incidence of ledging. Working lengths and master apical file sizes were not found to be significant variables. The main factor consistently related to the presence of ledges was canal curvature. The number of ledged canals increased significantly after 20 degrees and surpassed the number not ledged after 30 degrees. Multiple regression with the use of the five categories as the dependent variables and ledging as the independent variable resulted in an r = 0.397 and F = 12.216, p less than 0.0001. Curvature was found to have the highest significant t value (7.412) followed by "teeth" (2.471), whereas no other categories were identified as being significant. All the determinants for ledging were not identified with this study, and further research is indicated. PMID- 2216388 TI - Microleakage associated with retrofilling of the apical two thirds with amalgam. AB - In this investigation the effect of increasing the thickness of amalgam retrofilling on its sealing ability was studied and compared with the sealing ability of the laterally condensed gutta-percha with a sealer. The apical two thirds of the canals of 118 upper central incisors, filled with laterally condensed gutta-percha, were sealed with amalgam. Amalgam retrofills were also used to seal the apices of the roots of six teeth that had no other filling in their canals. The effectiveness of both techniques was determined by their ability to inhibit the penetration of methylene blue dye for the periods of 24 hours, 1 week, and 1, 3, and 6 months. At 24 hours both materials showed comparable sealing ability. However, the sealing ability of laterally condensed gutta-percha was significantly better than that of amalgam from the 1-week period until the end of the study. The depth of marginal penetration around both materials increased with time. The amount of the dye penetration increased acutely around amalgam, whereas its increase around gutta-percha was more uniform. At the end of the study, specimens retrofilled with amalgam exhibited total dye penetration that exceeded the full thickness of amalgam (6 mm) and spread into the root canal space. On the other hand, the mean value for marginal penetration of the dye around the laterally condensed gutta-percha was 2.6 mm at the end of the study. The present investigation proved beyond doubt that the use of any thickness of retrograde amalgam to seal the apex, with no other filling within the canal, invites failure. PMID- 2216389 TI - Fine-detail panoramic radiography by free-focus radiography. A clinical demonstration of diagnostic radiographs. AB - Previous comprehensive clinical studies have shown that free-focus radiography (FFR) may be used to improve image detail and diagnostic value in panoramic radiography of the teeth and jaws. This study demonstrated the clinical image quality in fine-detail panoramic FFR surveys relative to conventional surveys made by rotational panoramic or intraoral radiography. Cases of particular diagnostic interest with respect to common dental disease and changes in the jaws were included. The radiographic area of diagnostic interest depicted in FFR surveys generally resembled that of conventional dental radiographic surveys with the use of intraoral films rather then those of conventional rotational panoramic surveys. PMID- 2216390 TI - Transcranial radiographic and tomographic analysis of the lateral and midpoint inclined planes of the articular eminence. AB - A radiologic study of the articular eminence was performed on 10 skulls by means of tomograms and transcranial radiographs. Angulation of the articular eminence at the lateral and midpoint inclined planes was measured from the radiographs and compared with direct anatomic measurements. With both radiographic methods, the results showed no significant difference between left and right side measurements. The mean angulation of the midpoint inclined plane was significantly greater than that of the lateral inclined plane with both techniques. With transcranial radiographs, the angulation values were the same as the direct anatomic measurements despite a 25-degree change in skull orientation required for the radiographic method. In the tomographic study, all measurements corresponded with the anatomic and transcranial measurements except that angulation of the lateral inclined plane differed slightly from the direct anatomic measurement. The results show that both tomography and transcranial radiography are adequate for visualization of the midpoint region. However, tomography is preferable for viewing the lateral aspect of the articular eminence. PMID- 2216391 TI - Rubber base impression material. PMID- 2216392 TI - Maxillary lateral incisor with two developmental grooves. PMID- 2216393 TI - Complication in nasogastric tube placement after a gunshot wound to the face. PMID- 2216394 TI - Fusion of a third molar with an invaginated supernumerary molar. PMID- 2216395 TI - Aerobic bacterial contamination in dental materials. AB - Current concern about disease transmission points out the need for better infection control in dentistry. The purpose of this study was to test samples of dental materials in factory-sealed containers for aerobic bacterial contamination. Multiple unopened containers of 12 different dental materials were obtained from the dental school dispensary. Samples were removed from each container and incubated at 38 degrees C in standard broth medium for 1 week. Those that exhibited visual signs of possible bacterial growth were subjected to a Gram stain for verification. The results of that test indicated that 20% to 30% of the samples of alginate, glass ionomer cement and base powders, and retraction cord contained bacterial contamination. The remaining eight dental materials exhibited no apparent bacterial growth. Thus viable aerobic organisms were found in samples from 4 of 12 dental material products. PMID- 2216396 TI - Prevalence of shovel-shaped incisors in Saudi Arabian dental patients. AB - The prevalence of maxillary incisor shoveling was studied radiographically in 990 Saudi patients. According to the radiomorphologic characteristics, a new classification was developed and shovel teeth were categorized. The findings of this study showed 9% shovel-shaped incisors; among those, 4% were central incisors and 5% were lateral incisors. Frequency of dens invaginatus occurrence with the shovel-shaped incisors was also investigated. Eight percent of shovel shaped incisors showed presence of dens invaginatus. Prevalence was found to be 4% in central shovel-shaped incisors, whereas that in lateral shovel-shaped incisors was 11%. PMID- 2216397 TI - Tibial defects. Reconstruction using the method of Ilizarov as an alternative. AB - Although used in the USSR since the 1950s, the method of Ilizarov has only recently been employed in North America to manage bone defects. Seven cases of patients with tibial bone defects are presented (five with deep infection) that were treated by gradual compression at the defect with one or two transported tibial segments that not only filled the tibial defect but preserved or regained the original bone length. Six of the seven patients had their defect obliterated while leg length was maintained. The method is minimally invasive, allows immediate weight-bearing and permits modifications in strategy while treating the bone defects but requires close attention to detail and has a steep learning curve. PMID- 2216398 TI - Nonunion and malunion of fractures. PMID- 2216399 TI - Tibial nonunions. Treatment tactics with the Ilizarov method. AB - The key to the success of the Ilizarov method is that the rigid systems, such as plates and traditional external fixators that bypass the nonunion, have been replaced by the axially elastic system of Ilizarov. The cyclic axial telescoping mobility, not rigidity, at the nonunion or fracture site is an important requirement for the formation of reparative callus. As we gain more experience with the method, we find ourselves capable of solving increasingly more difficult problems with a level of success rarely, if ever, achieved with more conventional methods. PMID- 2216400 TI - The use of the Ilizarov concept with the AO/ASIF tubular fixateur in the treatment of segmental defects. AB - For the treatment of segmental defects of less than 4 cm, cancellous autografting remains the treatment of choice. Pedicled or free cortical grafts (fibula, ribs, iliac crest) often are not strong enough, particularly when used in the femur. Allografts, especially appealing because of the theoretic unlimited supply, should not be considered for segmental diaphyseal defects because they remain dead spacers, remodelled only very slowly and incompletely, and are often complicated by late infection. The technique of distraction histogenesis used by Putti and Anderson, improved and further differentiated towards corticotomy and fragment transport by Ilizarov, is a further possibility of treating long, segmental bone defects. Already clinical and experimental data clearly show that the effect of distraction histogenesis can be obtained using many different types of external fixators. Therefore, we should use as simple a fixator construction as possible. The standard unilateral sagittal frame we suggest is derived from a two-tube AO fixator using only a few additional elements. The majority of cases with segmental defects and minor additional axial or rotational deformities (which can be corrected primarily) can be treated with such a fixator. The quality of the regenerate may be improved with a motorized, continuous transport system and by better soft-tissue coverage using early flaps. Interface healing is very probably improved by cancellous grafting and internal fixation after the transport period, thus decreasing the fixator time. PMID- 2216401 TI - Treatment of malunions and mal-nonunions of the femur and tibia by detailed preoperative planning and the Ilizarov techniques. AB - Internal fixation has been the mainstay of treatment for post-traumatic deformities. External fixation has been used for correction of deformity in malunions and mal-nonunions. Treatment goals of achieving complete deformity correction with restoration or improvement of function were successful in this very complex group of malunions despite the numerous problems, obstacles, and complications of treatment. PMID- 2216402 TI - Preoperative planning for the treatment of nonunions and the correction of malunions of the long bones. AB - A detailed analysis of the steps of preoperative planning as employed in our clinic has been presented. We have found these techniques to be of great value in anticipating the requirements that must be fulfilled to correct malalignments and obtain healing when the malalignments occur alone or are associated with nonunion. Besides helping one to decide where a malalignment is best corrected to anatomically match the normal extremity, tracings aid in allowing the surgeon to appreciate the kinetics of the operative procedure, as well as to define the best methods of stabilizing the resulting correction. PMID- 2216403 TI - Treatment of tibial malunions and nonunions with reamed intramedullary nails. AB - Reamed intramedullary nailing is an effective, relatively low-risk technique for the management of delayed union, nonunion, and malunion of the tibia. Closed technique should be used where possible and open realignment, when necessary, should be executed with minimal dissection. Bone grafting is rarely indicated. The use of interlocking nails provides an added degree of security in the control of rotation. PMID- 2216404 TI - The treatment of nonunions and pseudarthroses of the humeral shaft. AB - In summary, if one follows the AO/ASIF principles of open reduction and stable internal fixation of nonunions and pseudarthroses of the humerus, mostly with plate fixation supplemented by shingling or petaling, cement for loose screws when necessary, and bone grafting of defects or atrophic nonunions, then successful healing with one operative procedure can be achieved in over 95%, with almost full correction of preoperative deformity. Return of useful function and range of motion can also be achieved in 75% to 90% by early active exercises, physiotherapy, and occasional continuous passive motion, supported by hinged braces or cast braces in the postoperative period until union occurs. Union was achieved in an average of 6.6 months after the operative procedure. PMID- 2216405 TI - Intraarticular malunions and nonunions. AB - The principles of intraarticular fracture care and stable internal fixation, when applied to intra-articular nonunions and malunions, can result in the restoration of an amazing function to joints that seem almost totally doomed to either an arthrodesis or an arthroplasty. The high degree of success achieved in almost all cases illustrates the amazing recuperative powers of human joints once articular cartilage congruence and stability is re-established together with correction of axial deformities and the mobilization of joints. PMID- 2216406 TI - Pauwels osteotomy for nonunions of the femoral neck. AB - The concept of the Pauwels osteotomy seems to be a valuable method of treating nonunions of the femoral neck. If there is concomitant avascular necrosis, the involved area should be small and the patient younger than 60 years old. PMID- 2216407 TI - Diagnosis and treatment of nonunions and malunions of acetabular fractures. AB - The surgical treatment of nonunions and malunions of acetabular fractures is often a challenge. The diagnosis of a nonunion or malunion rests on clinical and radiologic examination. Apart from the union troubles involving only one column, all other cases justify the use of the extensile approach. PMID- 2216408 TI - Chemical activity of simple basic peptides. AB - Alternating all-L poly(leucyl-lysyl) increases markedly the rate of hydrolysis of oligoribonucleotides. Pure D poly (leucyl-lysyl) is as active as the all-L polymer. The homochiral polypeptides adopt a beta-sheet structure when complexed to the oligonucleotides. Alternating poly(D,L-Leu-D,L-Lys) made of racemic amino acids is much less efficient and is unable to adopt a beta-sheet structure. A set of alternating poly (leucyl-lysyl) ranging from the racemic to the homochiral all L polymer has been checked. Their conformations can be described as a mixture of random coil and beta-sheet conformations, the amount of beta-sheet increasing with the optical purity of the polymer. The hydrolytic activity follows the proportion of beta-sheets, suggesting that the chemical activity is related to the geometry of the chain. Short peptides were prepared in order to evaluate the critical chain length required for the hydrolytic activity. A decapeptide is long enough to present 90% of the activity of the corresponding polypeptide. PMID- 2216409 TI - Energy-rich glyceric acid oxygen esters: implications for the origin of glycolysis. AB - The apparent Gibbs free energy change of hydrolysis (delta G degrees', pH 7) of the 2- and 3-O-glyceroyl esters of 2- and 3-O-L-glyceroyl-L-glyceric acid methyl ester were measured at 25 degrees C. The 2- and 3-glyceroyl esters were found to be 'energy-rich' with delta G degrees' values of -9.1 kcal mol-1 and -7.8 kcal mol, respectively. This result indicates that the analogous 2- and 3-glyceroyl esters of polyglyceric acid are also 'energy-rich' and, therefore, could have acted as an energy source for primitive phosphoanhydride synthesis. PMID- 2216411 TI - The revised genetic code. AB - Recent findings on the genetic code are reviewed, including selenocysteine usage, deviations in the assignments of sense and nonsense codons, RNA editing, natural ribosomal frameshifts and non-orthodox codon-anticodon pairings. A multi-stage codon reading process is presented. PMID- 2216410 TI - Phylogenetic tree of tRNAs using a simple algorithm. AB - A simple method for phylogenetic tree construction is described. In this method each node is calculated considering the distance between the elements and the difference between these elements and an average element, allowing the selection of the most probable node. Two examples of tRNA phylogenies (E. coli set and Phe family) are analyzed, giving both reliable trees. Data from these dendrograms give support to the idea of an early cloverleaf arising. PMID- 2216412 TI - [Bone scintigraphy in breast cancer: a ten-year follow up study]. AB - The value of bone scanning in the primary staging and clinical course of breast cancer was studied in a 10-years follow-up. Bone metastases (BM) were detected at the time of primary diagnosis in 6.8% of the patients. After primary therapy, the skeleton was the first site of the relapse in 42% of the cases. During the follow up, BM were revealed in 25% of 623 patients a mean of 22.3 months after the operation. BM were manifested in 17% of the cases with small primary (pT1) tumors and negative axillae. Forty-three percent of the patients had no symptoms at the time of BM diagnosis. The mean survival after the appearance of BM in 163 patients was 18.2 months. Thirteen patients survived more than 5 years after the diagnosis of BM. The routine use of bone scanning is suggested at the time of primary diagnosis, and then yearly in a minimum 5-years period, independently of the symptoms. PMID- 2216413 TI - [Distribution of lymphocyte subpopulations and plasma cells in the colonic mucosa of children with ulcerative colitis]. AB - The distribution of lymphocyte subpopulations and plasma cells of the colonic and rectal mucosae were studied in eight children with ulcerative colitis and 12 healthy controls. In four patients the examinations were also carried out 3 months after the beginning of treatment. No difference in the number of intraepithelial lymphocytes was found between the patients and controls. The majority of these cells were T-cells, and among them the suppressor/cytotoxic cells were preponderant. In the lamina propria of both untreated and treated patients the numbers of T-cells, helper T-cells, and B-cells were elevated compared to controls. In the patients the number of IgG-containing cells was three times that of the controls; the number of IgE positive cells was also elevated. The numbers of IgA- and IgM-containing cells were not different from that of the controls. The results suggest that in ulcerative colitis the place of primary immunological processes inside the large bowel mucosa is the lamina propria. PMID- 2216414 TI - [Prenatal ultrasonic diagnosis of a dicephalic fetus in the 18th week of pregnancy]. AB - The authors report a case of conjoined twins (dicephalus) detected antenataly in the 18-th week of pregnancy by routine ultrasound screening. The pregnancy was terminated because this congenital malformation is incompatible with extrauterin life. The embriopathological examination confirmed the prenatal diagnosis. The ultrasonographic criteria are discussed and the importance of early diagnosis is stressed. PMID- 2216416 TI - [Thoughts on Orvosi Hetilap and other subjects. "Solvitur acris hiems..." (Horatius) (correction of Martialis)]. PMID- 2216415 TI - [Prevention of rabies (experience of the past, possibilities of the future)]. AB - The authors review the history of rabies prevention, the current national and international data. Neurologic adverse effects of the Hempt vaccine are discussed. Medical histories of two patients are demonstrated, one suffered of serious complication of the vaccine; the other died of rabies. Indications of vaccine Rabivac and issues about it's administration are outlined. The possibilities of the therapy are discussed in brief. PMID- 2216417 TI - [More efficiency!]. PMID- 2216418 TI - [Protective action of allopurinol infusion against reperfusion arrhythmia during thrombolytic therapy of acute myocardial infarction]. PMID- 2216419 TI - [Different sensitivity to acid reaction of the AIDS virus and virus-producing cells: clinical conclusions]. AB - Sensitivity of the cell-free human immundeficiency virus type 1 (HIV-1) and its producer cells was Studied in acidic media between pH 7.4 and 4.9 vitro. The cytopathic effect, reverse transcriptase activity and p24 antigen production by survived viruses were monitored in indicator cell cultures. It was established that, the cell-free HIV-1 particles are very sensitive to acidity. Between pH 7.4 and 6.0 they loose infectivity gradually, but this process is irreversible under pH 6.0 and subsequent neutralization cannot restore lost infectivity. However, viability, of virus producer cells is hardly affected between pH 7.4 and 4.9, but their ability to release infectious particles is lost gradually, similarly to the case of cell-free viruses. Neutralization of the media after treatment results in gradual restoration of releasing infectious viruses. These data explain that, cell-free HIV-1 looses infectivity in the acidic vagina or does on the skin, but infectivity is preserved in the blood, semen, rectum and breast milk being neutral or slightly alcalic. Virus carrier or producer lymphocytes by any route of infection can survive such protective mechanism of the body. PMID- 2216420 TI - [Gastrointestinal angiodysplasia]. AB - 8 cases of gastrointestinal angiodysplasia are reported. It can be stated on the analysis of these cases, that the angiodysplasia can be the cause of unexplained GI hemorrhages, and in the majority of cases the visceral angiography provides diagnostic evidence. The angiodysplasia can be observed frequently in association with liver cirrhosis and aortic valvular stenosis. Surgery is regarded as the best method of treatment. Subsequently the careful resection rebleeding and development of newer angiodysplasia can occur. PMID- 2216421 TI - [Weather front sensitivity as an influencing factor in the onset of labor]. AB - The connection between meteorological stimuli and the onset of labor was examined on the basis of the patients' front-sensitivity. Front-sensitivity was tested by a questionary containing 60 questions. Converse relation was observed between the degree of sensitivity and the gestational age. A sudden rise of onsets of labors could be shown during frontal changes, occurred after meteorologically quiet periods. During frontal changes the ratio of onsets of labors rose significantly among those patients who were sensitive tho the given front. This effect could be observed during a longer period of frontal influence. By the authors opinion also meteorological stimuli can be regarded as one of the factors, determining the actual date of onset of labor among front-sensitive women. PMID- 2216422 TI - [Primary lymphoma of the bladder]. AB - The authors present the case of a 74-year-old man in whom bladder tumor was detected the reason for haematuria. The histological investigation of transurethral resected pattern showed lymphocytic lymphoma. In possession of the histological finding detailed haematological examination has been carried out, the patient was without evidence of lymphoma dissemination. He received multichemotherapy (6 courses) and locoregional cytostatic therapy and complete clinical remission was detected. The authors report our experience with extranodal bladder lymphoma included diagnostic and therapeutical notes as well as a review of the relevant literature. PMID- 2216423 TI - [Ignac Semmelweis--librarian of the faculty library at the Pest Medical School]. PMID- 2216424 TI - [Public health in Israel]. PMID- 2216425 TI - [To resuscitate of not?]. PMID- 2216426 TI - [Problems of thrombotic thrombopenic purpura and hemolytic uremic syndrome]. PMID- 2216427 TI - [Clinical aspects of zinc]. AB - In the literature an increasingly large body of evidence has revealed disturbances of zinc metabolism and a consecutive zinc deficit in a broad spectrum of chronic diseases. The authors call attention to the therapeutic benefit of zinc substitution mainly in chronic hepatic diseases, pancreatitis and colitis, as well as in diabetes and in several cases of immunodeficiency with various complications. Since suitable preparations are not available on the market 'possibilities concerning zinc substitution are rather limited. There is a real need for completing our therapeutic arsenal with an up-to-date zinc preparate, possibly in combination with a magnesium compound. PMID- 2216429 TI - [CT anatomy of the sella turcica and its environment]. AB - If MRI is not considered because of its limited capacity, computed tomography has become an exclusive diagnostic method in recent years in our country for the radiologic visualization of the sella turcica and its vicinity. Interpretation of the findings of this method lies on the knowledge of normal anatomical situations and variations. In direct coronal sections the hypothalamus, pituitary gland, suprachiasmatic cystern, optic chiasm, infundibular recess, sellar flor and the nerves transversing the cavernous sinus are visualised. The axial sections are more suitable for the visualization of the posterior lobe of pituitary gland and dorsum sellae. The Meckel's cavity, infundibulum and the blood vessels around the sella turcica are seen in both sections. The paper presents findings on the optimal CT evaluation of the above anatomical structures and variations as related to their diagnostic value. PMID- 2216428 TI - [Diagnosis and treatment of thromboembolic diseases of the right heart]. AB - Right heart thrombosis (RHT) was found by 2D-echocardiography in 8 cases. Clinical suspicion of RHT could be documented in only 3 patients, while in the other 5 cases syncope, low output syndrome, essential pulmonary hypertension, cerebral embolism or congestive heart failure was the clinical diagnosis on first presentation. Out of the 4 cases of mobile RHT of extracardiac origin 1 patient had an emergency operation, 2 patients died shortly after the 2D-echo diagnosis before treatment could have been started and 1 patient improved on anticoagulant treatment. RHT of intracardiac origin was due to a central line or a ventriculoatrial shunt in 3 cases and no source could be found in 1 patient. Complete recovery was achieved in 2 cases by medical, in one case by surgical management and in 1 patient medical and surgical treatment resulted in clinical improvement. In conclusion authors 1. consider 2D echocardiography necessary in the clinical setting of acute or chronic pulmonary embolism or "primary" pulmonary hypertension and 2. they recommend emergency operation in case of mobile large RHT detected by 2D-echocardiography. PMID- 2216430 TI - [Possibilities of the use of lymphoscintigraphy in head and neck surgery: introductory studies]. AB - The results of a pilot study of head and neck lymphoscintigraphy are presented. The study was performed in 35 cases with technetium-99m-labelled microcolloid. The scintigraphic observations of the intact and tumorous neck are presented. The results of this pilot study suggest that this method might create the base of a nonspecific additional diagnostic tool. PMID- 2216431 TI - [Subscapular liver hematoma and liver hemorrhage in neonatal age]. AB - By analysing their newborn patients of 15 years the authors confirm the earlier observation, that the subcapsular haematoma is a common finding at postmortem examination of the newborns dying during neonatal period. The association of the pathological symptoms of hypoxic origin of the other organs observed at autopsy and the decreasing incidence of subcapsular haematoma as a results of obstetrical and neonatal intensive care make this disease of hypoxic origin probable. In spite of common subcapsular haematoma the haemorrhage of liver causing haemascos is relatively uncommon. In their five patients suffering from liver rupture they observed two types of this (immediate and delayed rupture of liver's capsule), which also differed from one another in their clinical picture. They are drawing attention to general use of ultrasound in diagnostics which means a new chance to diagnosis in alive of both types. PMID- 2216432 TI - [Simultaneous occurrence of lupus erythematosus and desquamative interstitial alveolitis]. AB - Several subtypes can be distinguished within the disease lupus erythematosus according to the clinical appearance, serological and histological findings. With their case reports the authors wish to present that there is no definitive dividing line among them in practice, but transitional appearances and forms also exist. PMID- 2216434 TI - [Addenda to the article "Genetic and Ontogenic Analysis of Cases of Darier's Disease"]. PMID- 2216433 TI - [Views of medical students on the development of public health and on medical ethics]. PMID- 2216435 TI - [Current problems and complications of extensive uterine and pelvic lymph node excision for cancer of the uterus based on a 25-year case load]. AB - The authors studied the complications and other current problems of surgery of 212 cases subjected to Wertheim-Okabayashi operation. Of them 118 were cervix cancer in stage I and 90 in stage II and 4 were cancer of the uterus body in stage II. Two cases of operation death, 1 case of ureter injury and 1 case of large vessel injury occurred. Four ureteral and 1 late rectal-vaginal fistula developed. Difficulty of urination was observed in 49 cases. Those who consider surgical monotherapy best, hold the postoperative percutaneous irradiation necessary only in cases of metastases of the lymph nodes. PMID- 2216437 TI - [Laryngeal lipoma as a manifestation of lipomatosis]. PMID- 2216436 TI - [Effect of physical training on children after reconstructive heart surgery]. AB - The authors composed a programme of physical training for children with congenital valvular defect. The training programme was applied before and after the heart operation. Two years after a successful reconstructive heart operation the fitness condition of 40 children was examined. The average age of the children was 8.0 +/- 3.6 years. Twenty of the children participated and 20 did not participate in the programme. The physical condition of the children who took part in the training was found to be significantly better than that of the others without training. PMID- 2216438 TI - [Isolated right ventricular infarction]. AB - Generally, right ventricle infarction is accompanied by left ventricle infarction. Isolated right ventricle necrosis is rare. Among 1707 patients with 6 week-old myocardial infarction there were 2 cases with isolated right ventricle infarction. Diagnosis based on pathologic Q waves in right precordial chest wall leads, radionuclide and echocardiographic observations. In one case, diagnosis was supported by coronary angiography, too. PMID- 2216439 TI - [Ignac Semmelweis]. PMID- 2216440 TI - [Centenary of the birth of Andras Daday]. PMID- 2216441 TI - [The CELLADAM test and the physician's conscience]. PMID- 2216442 TI - [The interleukins ]. AB - Immune response is regulated by a number of soluble mediators. Interleukins belong to these mediators, as a well defined group of regulatory molecules. Interleukins are necessary for the differentiation and activation a T and B lymphocytes and other cells. They play an important role in inflammation: they cause fever, leukocytosis etc. Some interleukins are being used as therapeutic agents. PMID- 2216443 TI - [The Angelman or "happy puppet" syndrome]. AB - A case of Angelman's or "happy puppet" syndrome is described and detailed analysed, first time in our country. The literature is reviewed. The diagnostic criteria are presented. Evoked potential study and more than two years long EEG follow-up results are discussed. The unusual clinical feature of the described case is that epilepsy presented itself very early, in age of two weeks, by infantile spasms. It changed later to focal secunder generalised epilepsy. The EEG has been always abnormal during the follow-up, and the pattern has been changing by the age of the patient. On the other hand, the evoked potentials were all normals (BAEPs, VEP, SSEP CCT) "O"n the basis of the electrophysiological dichotomy the authors suggest a predominantly gray matter's disorder in Angelman's syndrome. They emphasize, that Angelman's syndrome has to be keep in evidence in the differential diagnosis of early infantile epilepsies. In the presented case the familial accumulation of movement's dyscoordinations, the dysmorphic features and subnormal intelligence of the brother support the possibility of the role of an autosomal recessive gene with different penetrance in the pathogenesis of Angelman's syndrome. PMID- 2216444 TI - [Femoral head necrosis]. PMID- 2216445 TI - [Pathological anatomy of femur head necrosis]. AB - Aseptic necrosis of the femoral head appears to have a number of etiological factors. The last steps of the pathogenetic course of events, however, is unclear. Histologically, small foci of marrow necrosis form repeatedly, particularly in the upper and medial zone of charge, and then fuse secondarily to larger areas. Secondary reparation events with ingrowth of sprouts of granulation tissue and neoformation of bone predominantly in connection with necrotic trabeculi are followed by renewed waves of necrosis, resulting in a most variegated picture in which the different phases can no longer be clearly differentiated. After the articular cartilage has been sequestrated and torn away, the uncovered spongious bone is exposed to the transforming influence of direct charge, with subsequent secondary osteoarthrosis. From the histological picture follows the modern conception of its pathogenesis: an intraosseous increase in pressure primarily infringes on the venous outflow and secondarily on the arterial inflow. These cyclic circulatory disturbances provoke the focal appearance of necrosis. As a result of this, "core decompression" follows as a therapeutic intervention that is successful in many cases. PMID- 2216446 TI - [Imaging diagnosis in femur head necrosis with emphasis on skeletal scintigraphy and magnetic resonance tomography]. AB - Early diagnosis and treatment of avascular necrosis (AVN) of the femoral heads improve the prognosis of this disorder. Of the different radiological studies available so far, none has been truly satisfactory. Conventional X-rays frequently show alterations in the femoral heads only in later stages. Early on these may be so subtle that they are overlooked by the examiner. Bone scintigraphy is more sensitive than conventional X-rays in the detection of early alterations, but there are still up to 18% negative studies in biopsy-proven femoral-head necrosis. The sensitivity of this method is also diminished when bilateral AVN is present. This is frequently the case even if only one hip joint is symptomatic. Computed tomography (CT) and single photon emission computed tomography (SPECT) are highly sensitive methods that are still not widely used for the diagnosis of AVN. With SPECT, clinical experience is still limited. A number of publications in recent years have revealed the excellent characteristics of magnetic resonance imaging (MRI) in showing the pathological processes in bone marrow and, in particular, AVN. This paper summarizes a few of these publications and our personal experience with MRI in AVN of the femoral head. Different cases examples are given. PMID- 2216447 TI - [Femur head necrosis in childhood]. AB - The natural history of avascular necrosis of the femoral head in children and adolescents shows significant differences compared to the course of this disease in adults. Depending on the remaining growth potential, even extensive damage of the femoral head can regenerate, as long as the epiphyseal growth plate is not involved in the process. Otherwise, the deformity will increase with time. Current knowledge on the etiology, natural history, diagnosis and treatment is described on Perthes' disease and other possible causes of avascular necrosis, such as CDH, epiphyseolysis of the femoral head, femoral neck fracture and some uncommon diseases. PMID- 2216448 TI - [Clinical and therapeutic concepts in ischemic femur head necrosis]. AB - Bone ischaemia can result from four mechanisms: (1) interruption of arterial inflow (e.g. after femoral neck fracture), (2) occlusion of venous outflow (possibly due to capsular distension), (3) intravascular arteriolar occlusion (as in sickle cell disease); (4) extravascular sinusoidal tamponade (e.g. in Gaucher's disease). Osteonecrosis following high-dosage corticosteroid administration or alcohol abuse could, theoretically, be due to either intravascular fat embolism or sinusoidal tamponade resulting from the marked fat deposition in the marrow. It is proposed here that, except in traumatic osteonecrosis, vascular insufficiency is part of a cycle of events resembling the familiar soft tissue compartment syndrome of the forearm or leg; no matter whether it started with venous stasis, arteriolar occlusion or capillary tamponade, the result is a diffuse and self-enhancing ischaemia involving all three haemodynamic abnormalities in a vicious circle. The very earliest stage of "idiopathic" osteonecrosis is characterised chiefly by marrow changes; for some (undetermined) period the ischaemic effects are potentially reversible-provided the vicious circle is broken by relieving the high intraosseous pressure. Effective management involves: (a) early diagnosis by MR imaging, measurement of intraosseous pressure and venography: (b) decompression of the bone, and (c) elimination of the etiological factor. Later stages of osteonecrosis cannot be treated by decompression and will need realignment osteotomy, prosthetic replacement or arthrodesis. PMID- 2216449 TI - [Joint-preserving osteotomy in segmental femur head necrosis]. AB - Joint-preserving osteotomies for segmental necrosis of the femoral head are clinically important, as necrosis often occurs in relatively young people in whom one is hesitant to perform femoral head replacement. The principle in all joint preserving osteotomies is to remove the necrotic area from the zone subject to load, thereby guarding against indentation of the joint surface. The most universal and most frequently indicated osteotomy is intertrochanteric valgus flexion osteotomy with ventral capsule resection. The result of the operation depends mainly on the extent of the necrosis. If the angle of the necrosis is under 200 degrees, the hip joint can be preserved with great precision and in a good enough state to allow joint replacement to be postponed for many years. PMID- 2216450 TI - [Role of core decompression as treatment method for ischemic femur head necrosis]. AB - Nontraumatic ischemic necrosis of the femoral head remains a source of much controversy. The etiology is also controversial. Possibilities are: hypertrophy of intraosseous structures (lipocytes, hematopoietic elements), creating intraosseous hypertension; alcohol and steroids as toxic agents; circulating fat globules embolizing the microcirculation of the metaphysis. The disease appears most frequently in young adults, but no satisfactory nonoperative treatment modalities have been reported as yet. In 1971, Ficat and Arlet published their results on core decompression performed in 100 patients, with a follow-up of from 1 to 5 years. The results for those with stage I disease (n = 40) were good or excellent in 88% of the patients. The results for those with stage II disease (n = 16) were good or excellent in 69%. Based on current experience, the treatment is to be recommended for patients with pre-collapse stages 0, I and IIA of ischemic necrosis of the femoral head. For stage III disease, the procedure may reduce pain at night and at rest and can be considered in patients wishing to avoid total hip arthroplasty for a period of time. PMID- 2216451 TI - [Partial femur head necrosis in adults--results with intertrochanteric osteotomy and revascularization]. AB - Osteotomy and revascularization have both been used for many years in the therapy of partial aseptic necrosis of the femoral head in the adult. We first attempted a combination of the two techniques in 1978. Stress on the necrotic sector was relieved by intertrochanteric osteotomy, and the necrotic part of the bone was revascularized with a pedicled iliac crest bone graft based on the deep circumflex iliac vessels. Long-term results are now available in 45 hips in 38 patients, with a mean follow-up time of 32 months. Clinically, 71% of the hips were rated very good or good, and among those classed as stage II before surgery the results were rated as very good or good in as many as 90%. Subjective evaluation of the hips by the patients confirmed these results: 85% of the hips were judged to be optimal or markedly improved compared with before operation. Radiological evaluation showed further flattening of the femoral head in one case. A segmental collapse of the femoral head, i.e. stage III lesion according to Ficat, occurred in 2 hips with stage II preoperatively. In 6 hips with stage III necrosis preoperatively secondary arthritis developed. Computerized tomograms taken of all 25 hips from which metal implants had been removed showed signs of integration of the graft in 68%. Scintigraphy with 99-Tc-diphosphonate showed a homogeneous uptake in 42.8% and a non-homogeneous uptake in the remaining 57.2% of the cases. So-called photopenia was not observed in any of the hip joints treated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216452 TI - [Sugioka's trans-trochanteric osteotomy. Results of interventions 1975-1983]. AB - The long-term results of 46 Sugioka osteotomies are presented: In 22 patients no joint replacement had yet been necessary, and 17 hip joints had already been replaced by total hip prostheses. Of the 22 preserved joints, 12 were graded as clinically excellent and good, 10 as fair or poor. The radiological course showed worsening osteoarthritic changes in almost all cases. In the "survival curve" for the Sugioka osteotomy in the group with 17 total hip prostheses the most significant slope can be seen during the first 3 years postoperatively; between 5 and 10 years there are no failures; and then the curve descends again. Fair and poor results are noted most frequently between 6 and 10 years after the operation in the group of 22 patients with no joint replacement. The preoperative extent of necrosis and the radiological stage are the main factors determining the result. Over the years it has been possible to define a narrow spectrum of indications: the greatest benefit is obtained in young, cooperative patients with necrotic sectors of about 90 degrees and good function of the hip joint. PMID- 2216453 TI - [Total prosthesis arthroplasty in femur head necrosis]. AB - In young patients with advanced necrosis of the femoral head, the short- and medium-term results of total prosthesis arthroplasty are the most satisfactory. However, the prospect of aseptic loosening hangs over such arthroplasties like Damocles' sword. Reports from the literature suggest that, in addition to the age of the patient, there is also an endogenous factor that can be responsible not only for the etiology and pathogenesis of the necrosis, but also for the early loosening of the prosthesis. We have followed up 54 patients (73 hip joints) who had total hip replacement as a result of necrosis of the femoral head between 1976 and 1988. Altogether, 3 acetabular and 5 femoral shafts had to be replaced (7 patients). This corresponds to a loosening rate of 10% after an average of 4.9 years. Hence, the prosthesis changing rate is lower than that reported by other authors, but is still higher than in patients with coxarthrosis. Only 2 of 52 cemented shaft prostheses had to be replaced; the average age of these patients was 61.4 years. Of the 21 cement-free shaft implantations, 3 had to be replaced, the average age of these patients being 42.9 years. The fact that the average age of the latter patients was lower may be the reason for the revision rate not being significantly higher for the non-cemented shafts. In view of the fact that necrosis of the femoral head can rapidly result in the patient becoming an invalid if it is allowed to follow its natural course, hip joint prostheses should also be offered to younger patients. PMID- 2216454 TI - Protein-binding elements in the promoter region of the mouse p53 gene. AB - p53 is a cellular protein whose expression plays a crucial role in the regulation of cell proliferation and of neoplastic processes. p53 mRNA levels in mouse fibroblasts can be elevated in response to TPA and to serum stimulation. The promoter region of the p53 gene contains a conserved element which is highly homologous to the consensus AP1 binding site (7/8 matching bases). This AP1-like site, denoted the PF1 site, confers upon a heterologous promoter ability to respond to elevated expression of c-jun. Furthermore, the PF1 site binds protein(s) in a specific and serum-induced manner. Unexpectedly, this factor is most probably not AP1, as evident from the inability of an authentic AP1 site to compete the binding efficiently, as well as from the failure of purified AP1 to bind to the PF1 site. Hence, PF1 may be a novel AP1-related transcription factor. In addition, the 5' region of the p53 gene also contains an NF1 binding site, whose location suggests a possible regulatory role. PMID- 2216455 TI - Specific expression of the ret proto-oncogene in human neuroblastoma cell lines. AB - The expression of the ret proto-oncogene (proto-ret), which possibly encodes two isoforms of a receptor-type tyrosine kinase, was examined in human tumor cell lines. Expression of the proto-ret mRNA was detected in all 11 neuroblastoma cell lines examined. The level of mRNA varied more than 100-fold in these neuroblastoma cell lines and was particularly high in three of them. On the other hand, 19 non-neuroblastoma tumor cell lines derived from solid tumors and a human diploid fibroblast cell line did not express any detectable levels of proto-ret mRNA. No remarkable amplification of the proto-ret or gross structural changes in the coding region were found in these neuroblastoma cell lines. The specific expression of the proto-ret in neuroblastomas suggests that the proto-ret product may have a role in cellular functions specific to neuroblastoma cells. PMID- 2216457 TI - tyk2, prototype of a novel class of non-receptor tyrosine kinase genes. AB - We previously identified a novel protein tyrosine kinase gene, tyk2, by screening a human lymphoid cDNA library with a tyrosine kinase domain specific c-fms restriction fragment under low stringency hybridization conditions. We have now isolated and sequenced a full length tyk2 cDNA clone; demonstrated that this gene is widely expressed in hematopoietic and non-hematopoietic cell lines; and mapped it to chromosome 19p13.2. The cDNA clone is 4176 nucleotides long and codes for a putative protein with a molecular weight of 134 kilodaltons. Hydrophobicity analysis of our sequence does not identify a transmembrane domain, which is found in all members of the receptor class of protein tyrosine kinases; nor can we detect an SH2 domain, found in all previously identified non-receptor protein kinases. We therefore propose that tyk2 is the prototype of a new class of non receptor protein tyrosine kinases. PMID- 2216456 TI - Mutation of the p53 gene in human soft tissue sarcomas: association with abnormalities of the RB1 gene. AB - Soft tissue sarcomas have been examined for alterations in the p53 gene. In six sarcomas, loss or rearrangement of both alleles of this gene was detected while in a further seven sarcomas, point mutation or absence of transcription of the p53 gene was observed. Abnormalities of the p53 gene were found in several classes of soft tissue sarcoma, including leiomyosarcomas, rhabdomyosarcomas and malignant fibrous histiocytomas. Our studies also show that abnormalities of the RB1 suppressor gene and of the p53 gene frequently occur together. These results are consistent with the idea that the p53 gene is a tumour suppressor gene and indicate that coincident inactivation of more than one tumour suppressor gene may, in some cases, be required for tumour development. PMID- 2216458 TI - The human ETS-2 gene promoter: molecular dissection and nuclease hypersensitivity. AB - The human ETS-2 gene is a homolog of the v-ets oncogene of the E26 virus, coding for a 56 kilodalton nuclear protein. Herein we characterize the ETS-2 gene promoter, using a series of deletion constructs. Analysis of the nucleotide sequences from -3600 bp to +141 bp reveal that the region -159 bp to +141 bp is absolutely essential for maximum promoter activity. This region includes half of the lengthy polypyrimidine (CT) tract of the ETS-2 promoter, one Sp1 binding site and the GC element proximal to the initiation site. This CT tract is able to increase in an orientation independent manner, the transcription from alpha globin promoter. Several S1 hypersensitive sites are found to be located in this promoter region, using chromatin and supercoiled DNA, in close proximity with cis regulatory elements. Our results indicate that an unusually long (approximately 250 bp) CT tract is necessary for ETS-2 transcription and this tract can also serve as a transcription activator using a heterologous promoter. PMID- 2216459 TI - Amplification of the c-myc and the pvt-like region in human multiple myeloma. AB - Genetic alterations that lead to the clonal expansion of differentiated cells in multiple myeloma have still to be elucidated. Many chromosomal aberrations have been found, but until now, none of them is typically associated with multiple myeloma. In search for genetic defects in multiple myeloma we studied the structure and expression of the c-myc oncogene and the pvt-like region because of their frequent association with other B-cell malignancies. Here we report co amplification of the c-myc oncogene and the 5' part of the pvt-like region in two out of 26 cases of multiple myeloma. In both cases only kappa-light chains were produced. The amplification also manifested itself at the RNA level. Total RNA was analysed in one of these two cases showing abundant c-myc mRNA. In the same RNA sample we also detected a strong hybridizing band of about 7 kb, when the pSS.4 probe, representing the 5' part of the pvt-like region, was used. This band was not present in total RNA from normal bone marrow cells or bone marrow from multiple myeloma patients without the amplification of c-myc and the pvt-like region. Until now, transcripts of the pvt-like region were only found in a few human cell lines ranging in size from 1 to 11 kb. This is the first case in which a high expression of a +/- 7 kb transcript of the pvt-like region has been found in freshly obtained tumor material probably due to a pvt-amplification. The occurrence of abnormalities in the c-myc and the pvt-like region in multiple myeloma is a rare event and may be associated with the progression of this type of tumor. PMID- 2216460 TI - A raf/myc virus immortalized macrophage cell line which supports the growth of B cell and B-cell hybridomas. AB - Using a combination of raf and myc oncogenes co-expressed by the recombinant retrovirus J-2 we have generated and characterized a cell line which very efficiently supports the growth of B-cells and B-cell hybridomas. Murine spleen cells were cultured under in vitro immunization conditions favoring the short term proliferation of splenic B lymphocytes and infected with J-2 virus. Screening of immortalized spleen cell pools for the capability to support long term B cell growth in vitro led to the selection of a clonal cell line termed alpha ChyJ2. The presence of macrophage specific features and surface markers suggest that alpha ChyJ2 belongs to the macrophage lineage. alpha ChyJ2 cells constitutively produce low levels of IL-1 like activity and high levels of IL-6. Expression of specific mRNAs as well as production of IL-1 alpha, IL-1 beta and IL-6 are inducible with LPS. Expression or production of other cytokines including IL-2, IL-3, IL-4, IL-5, TGF beta and GM-CSF could not be detected. As the biological effects of alpha ChyJ2 supernatant cannot be fully explained by the described pattern of cytokine production, participation of other, yet uncharacterized, factors is possible. Using alpha ChyJ2 as feeder cells for in vitro as well as in vivo immunizations increased the number of antibody secreting B-cell clones 2 to 15 fold, respectively. PMID- 2216461 TI - Ability of the HPV16 E7 protein to bind RB and induce DNA synthesis is not sufficient for efficient transforming activity in NIH3T3 cells. AB - Previous studies have demonstrated that the HPV-16 E7 gene product encodes the major transforming activity of the virus in rodent cell systems. In this study we have generated a series of point mutations affecting the region of HPV-16 E7, which shows homology to adenovirus E1a conserved domain (CD)1. In conjunction with previously described mutants in the region of E7 with similarity to E1a CD2 and SV40 LT, we have investigated three known activities of the E7 protein; transformation, association with the cellular RB protein and induction of cellular DNA synthesis. The results show that RB binding correlates with the ability of E7 to induce cellular DNA synthesis and mediate cell transformation. In addition an unidentified function of E7, which is necessary for transformation of NIH3T3 cells, but does not affect RB binding or the ability to induce cellular DNA synthesis, has also been demonstrated. This study therefore identifies two separate regions of the E7 gene necessary for transformation of established cells. One of these, in the region of E7 which shows similarity to E1a CD2 and LT, is required for RB binding and DNA synthesis. The other region important for transformation, in the N-terminus of E7, is separable from the RB binding/DNA synthesis function. PMID- 2216462 TI - Overexpression of matrix Gla protein mRNA in malignant human breast cells: isolation by differential cDNA hybridization. AB - Genetic alterations are involved in the development of human breast cancer. We sought to isolate genes that are differentially expressed or suppressed in cultured human breast carcinoma cells as compared to cultured normal human breast epithelial cells by employing differential screening of selected cDNA libraries. Analysis of several clones thus isolated revealed that the matrix Gla protein (MGP) gene is overexpressed in the breast cancer cell line 600 PEI, though is transcribed at lower levels in most other mammary derived cultures. MGP requires vitamin K dependent gamma-carboxylation for its known function and thus can be inhibited by vitamin K antagonists. This raises the possibility that MGP may be among those factors that when inhibited by vitamin K antagonists reduce metastases in experimental models. Among the gene whose transcription is consistently suppressed upon mammary transformation were fibronectin and the type I keratin, K14. Differential cDNA screening therefore is an effective method of identifying genes involved in various aspects of mammary cell transformation. PMID- 2216463 TI - Expression of P0- and P3-RNA from the normal and translocated c-myc allele in Burkitt's lymphoma cells. AB - We have studied the allele specific expression of c-myc P0- and P3-RNA in Burkitt's lymphoma (BL) cells. The steady state levels of P0-RNA show considerable variations in BL cells. Expression of P0-RNA was found to be restricted to the translocated allele, but could be induced by TPA from the normal allele. P0-transcription was particularly sensitive to inhibitors of protein synthesis compared to expression of P1-, P2- and P3-RNA. Transcription of P3-RNA is initiated in the first intron of the c-myc gene and has previously been described to be specific for translocated c-myc alleles in BL cells broken within exon 1 or intron 1. Here we show that P3-RNA is also expressed from an unrearranged c-myc gene. In the BL cell line Raji, substantial amounts of c-myc RNA are derived from the P3-promoter of the normal allele. This indicates that repression of the normal allele in BL cells does not include the P3-promoter. The potential coding capacity of P3-RNA is discussed. PMID- 2216464 TI - Human TRK proto-oncogene maps to chromosome 1q32-q41. AB - The chromosomal localization of TRK, a gene coding for a putative receptor molecule with an associated tyrosine kinase activity that we have found activated in 25% of patients with papillary thyroid carcinoma, was determined by Southern blot analysis of a panel of human-rodent somatic cells using a cDNA clone containing the entire human TRK proto-oncogene (Martin-Zanca et al., 1986). The TRK gene was assigned to chromosome 1. One hybrid that had retained only the short arm of the human chromosome 1 was negative. Subsequently, in situ hybridization of the same probe to human metaphase chromosomes localized the TRK gene to 1q32-q41. PMID- 2216465 TI - Malignant transformation of an infinite life span human fibroblast cell strain by transfection with v-Ki-ras. AB - To determine if human fibroblasts can be transformed into malignant cells by transfection of a K-ras oncogene, we transfected the provirus of Kirsten murine sarcoma virus (v-Ki-ras) into an infinite life span human cell strain, MSU-1.1, which has a normal morphology, is not anchorage independent, and has a stable, near-diploid karyotype. The transfected populations gave rise to distinct foci composed of morphologically-altered cells. The cells from several independent foci were isolated, propagated, and assayed for anchorage independence and/or tumorigenicity. They formed large-sized colonies in soft agar at a high frequency. Cell strains derived from colonies isolated from agar as well as focus derived cell strains were injected subcutaneously into athymic mice to test for tumorigenicity. One cell strain yielded myxoid fibromas, the rest produced well differentiated, progressively-growing, invasive, myxoid or spindle cell sarcomas. The karyotype of each of the cell strains tested, including cell strains derived from tumors, was identical to that of non-transfected MSU-1.1 cells. Two focus derived strains, and two cell strains derived from sarcomas produced from them, were tested and shown by DNA and RNA hybridization to contain and express the v Ki-ras oncogene. Radioimmunoprecipitation analysis showed that these strains expressed ras-specific p21 products not found in non-transfected MSU.1.1 cells. When injected intraperitoneally, a cell strain derived from a myxoid tumor gave rise to invasive myxoid tumors at various sites in the body. The same cell strain gave rise to invasive spindle cell sarcomas when injected into the tail vein of the animals. PMID- 2216467 TI - Mapping of the functional domains of the v-rel oncogene. AB - Previously, the v-rel oncogene was shown to code for a protein of 503 amino acids. The protein product of v-rel was identified as a 59 kDa protein (pp59v rel), phosphorylated predominantly on serine residues. Although the signal required for the nuclear localization of pp59v-rel in chicken embryo fibroblasts was identified, the regions of v-rel important for transformation have not been mapped. In this study, 12 linker insertion mutants of v-rel were constructed and tested for transforming activity. Seven linker insertion mutants which mapped between amino acid residues 29 and 275 abolished transformation. The remaining 5 mutants which contained linker insertion mutations between amino acid residues 332 and 459 transformed at wild type levels. The results of this analysis localize the functional domains of the v-rel oncogene to the N-terminus. Earlier reports have shown that pp59v-rel resides in a high molecular weight complex with several other cellular proteins. The transforming mutants co-precipitated the same set of cellular proteins when immunoprecipitated with v-rel antiserum. This indicates that all transforming mutants retained the ability to bind within the reported complex. PMID- 2216466 TI - Frequent activation of non-ras transforming sequences in neoplastic Syrian hamster cells initiated with chemical carcinogens. AB - Carcinogen-caused transformation of Syrian hamster embryo cells has been widely used as a model for experimental carcinogenesis. However, analysis of the molecular mechanisms of hamster cell transformation has been limited. To expand the understanding of the molecular basis of this system, 22 independently derived Syrian hamster neoplastic cell lines initiated with chemical carcinogens were screened for the presence of dominant transforming sequences by DNA transfection into mouse NIH3T3 cells. High molecular weight DNAs from 12 (55%) of these cell lines transformed NIH3T3 cells through serial transfection cycles. NIH3T3 transformants contained hamster-specific repetitive sequences, which co segregated with the transformed phenotype in successive transfection rounds. Results from Southern hybridization analyses and p21ras mobility assays indicated the presence of N-ras oncogenes, presumably activated by point mutations at codon 61, in 3 of the 12 (25%) transfection positive lines, all initiated with sodium bisulfite; non-ras transforming sequences were apparently activated in the remaining 9 (75%) lines. DNA prepared from NIH3T3 transformants derived from cell line 81C39 was analysed by Southern hybridization with a battery of 38 probes including non-ras oncogenes known to score as positive in the NIH3T3 assay as well as other retroviral and mammalian oncogenes. Each probe hybridized to DNA fragments showing the mobility characteristic of NIH3T3 protooncogenes, but failed to detect homolog sequences of hamster origin, even under hybridization conditions which allowed their detection in hamster DNA. Results show that ras activation occurs at a low frequency in hamster neoplastic transformation and strongly suggest that novel transforming sequences are activated, thus validating the use of this system for investigating the role of non-ras transforming sequences in neoplasia. PMID- 2216468 TI - Do long wavelength pass filters improve low vision performance? AB - It has been suggested that the wearing of band-pass tints may improve the contrast performance in certain ocular conditions. We examined this by measuring grating visual acuity (VA) for targets of various contrasts. The benefits of Corning CPF 511, 527 and 550 lenses, and neutral density (ND) filters were examined with and without the presence of glare. Generally, patients with anterior sector conditions showed improved performance with band-pass filters (not with ND filters). It is suggested that the filter reduces the scatter within the ocular media. People with retinitis pigmentosa or diabetic retinopathy rarely benefited. The CPF 511 most frequently improved VA followed by CPF 527 and 550 respectively. We suggest that a condition of glare is incorporated when assessing suitability with tints. PMID- 2216469 TI - Efficiency in reading with closed-circuit television for low vision. AB - A closed circuit television (CCTV) magnifier was used to measure the reading rates of nine fluent low-vision subjects. Performance was found to be dependent on field width, character size, and the number of characters displayed in line. A field width of 70 degrees and a mean of 24 characters were commensurate with the fastest reading rate. The optimal character size that elicited the fastest reading was determined for each subject. In seven of the nine subjects, this differed from the character size selected by chance at their initial CCTV sessions, prior to these experiments. A clinical procedure is recommended, which avoids inappropriate choice, and guides the examiner in achieving directly the most efficient CCTV reading conditions for each individual patient. PMID- 2216470 TI - Ocular dimensions and refractive power in Malay and Melanesian children. AB - A cross-sectional study of 753 Melanesian children in Vanuatu and 904 Malay children in Malaysia included measurement of refractive error and ocular dimensions. All children were between the ages of 6 and 17 years. The prevalence of myopia in Malay children was 4.3% at 7-8 years and 25.6% at 15-16 years with corresponding figures of 0.8% and 4.3% for Melanesian children. The range of refractive error was greater for Malay children at all ages. Mean refractive error for Malay children showed greater hypermetropia, together with a shorter axial length at 6 years, than Melanesian children, but at 17 years the situation reversed and Malay children had more myopia and longer axial lengths than their Melanesian counterparts. PMID- 2216471 TI - Accommodation and the nerve pathway to the ciliary muscle: a review. AB - Evidence has accumulated recently which challenges the conventional description of the parasympathetic division of the oculomotor nerve pathway to intraocular smooth muscles. It is claimed that the pathway from the midbrain to the ciliary muscle is direct and uninterrupted by a synapse in the ciliary ganglion. A similar, separate claim has been made regarding the innervation of the sphincter muscle of the iris. The weaknesses in the arguments supporting the revised versions are discussed in this review and they are rejected in favour of the conventional pathway. PMID- 2216472 TI - Effects of stimulus distance on measurements of dark convergence. AB - Dark convergence is often measured psychophysically by aligning two dichoptic stimuli, which are briefly flashed in a dark surround. In the present study, the effect of different stimulus parameters on dark convergence measurements was investigated. Chief among these was the effect of viewing distance (50, 100 and 500 cm) of the stimulus. Measured dark convergence was biased towards the actual viewing distance of the stimuli; this effect was stronger with bar stimuli than with point-and-line stimuli. Measured dark convergence depended on the viewing distance to a lesser extent if bar stimuli were observed through pin-holes (open accommodative feedback loop). The subject's knowledge of the viewing distance had a small but significant effect; the size of the nonius bars had none. To reduce artefacts due to the stimulus distance on psychophysical measurement of dark convergence, point-and-line stimuli should be used at a viewing distance of about 1 m. In this case, the effect of stimulus distance can be about 0.25 meter angle (ma), averaged over subjects, but it may be as large as 0.5 ms in some individuals. PMID- 2216473 TI - Proximal and cognitively-induced accommodation. AB - The aim of this study was to investigate proximally-induced accommodation (PIA) at two levels of cognitive demand. PIA was assessed by comparing the open-loop accommodative responses to stimuli located at viewing distances of 6 m (0.17 D) and 0.33 m (3 D), respectively. The vergence and accommodation loops were opened by subjects monocularly viewing the targets through a 0.5 mm pin-hole. PIA was measured while subjects either were encouraged to relax and listened to popular music, or performed a relatively demanding mental arithmetic task (counting backwards in sevens). The results indicated that for 4 of the 12 subjects examined, increased cognitive demand produced a marked (greater than +/- 1.00 D) change in the magnitude of PIA. This finding suggests the presence of an interaction between the output of proximally- and cognitively-induced accommodation in these subjects. Such an interaction may hinder attempts to examine individual, non-optical components of accommodation. PMID- 2216474 TI - Binocular summation in visually evoked responses and visual acuity. AB - Monocular and binocular transient visually evoked responses (VER) were recorded on 50 adult subjects using a pattern reversal stimulus (check size 5.5 min arc). The peak-to-trough amplitude of the VER wave was measured and compared with the subjective visual acuity (Landolt C). The binocular amplitude enhancement over the monocular amplitude was around 26% across the acuity range studied, whereas the mean binocular subjective visual acuity improvement was around 11.3%, but this varied from 1% at the high acuity end to 17% at the low acuity end of the range. PMID- 2216475 TI - A gradient-index ophthalmic lens based on Wood's convex pseudo-lens. AB - Although the Varilux type varifocal has been and still is very popular, research has been carried out on other methods of providing a progressive addition lens. This paper deals with the field of gradient-index optics. It includes a review of the literature related to the production of a gradient-index element and the theoretical analysis of concentric varifocals. A procedure is described to construct a varifocal lens, after that described by Wood in 1905, to produce lenses known as 'non-homogeneous cylinders' or 'pseudo-lenses'. The method is based on a diffusion process, taking place in half of the lens, and creates steps in the refractive index of the material. Experimental data are also given on the change of the spherical and cylindrical power, which indicate that the lens constructed is an optical system having a rotational symmetry in power, around a fixed point. PMID- 2216476 TI - Effect of illuminance on the directions of chromostereopsis and transverse chromatic aberration observed with natural pupils. AB - The direction of chromostereopsis observed with a natural pupil and the direction of the monocularly perceived disparity between coloured targets (F and C lines - 486 and 656 nm) have been measured in a sample of 30 subjects at 10 and 1000 lx. At both illumination levels approximately equal numbers of subjects perceived positive and negative chromostereopsis. When the ambient illumination was increased, a reversal in the direction of the chromostereopsis occurred for 16 subjects. For six of them a change from a positive to a negative chromostereopsis was observed, a pattern not reported in previous studies. In most cases at both high and low illuminance, there was an absence of perception of a monocular disparity (transverse chromatic aberration), although chromostereopsis was reported, indicating that binocular information can be obtained from sub threshold monocular disparities. At low illuminance, the lack of correlation between the direction of chromostereopsis and transverse chromatic aberration (TCA) may indicate that there may be a supplementary binocular factor in chromostereopsis. PMID- 2216477 TI - Tri-meridional analysis using arbitrary meridians. AB - The evaluation of the sphero-cylindrical components of curvature or refraction from measurements taken along three distinct meridians has been solved for various sets of three fixed meridians. A constraint of those solutions has been that the meridians of measurement are necessarily predetermined, which introduces an unwelcome restriction in experimental or clinical applications of tri meridional analysis. A new solution is presented (in three formats: analogue computer, graphical and algebraic), which enables any set of three meridians to be used for tri-meridional analysis. A computer program listing (in BASIC) is included. PMID- 2216478 TI - A general numerical method evaluating three-dimensional eye rotations by scanning laser ophthalmoscopy. AB - A general computational method is described to specify completely the rotational state of the eye in three dimensions by scanning laser ophthalmoscopy (SLO). The method uses the simplex algorithm to fit the eye's rotational parameters to data given by n individually selected ocular fundus landmarks before and after the eye rotation. The rotational parameters are expressed as the rotation vector and three spherical Euler angles. The method, which was implemented in the C programming language, can be applied for various eye movement measurements in clinical and laboratory environments, including SLO. PMID- 2216479 TI - Eye-tracking infra-red optometer. AB - An eye-tracking infra-red optometer has been developed to measure dynamic refractive power during slow horizontal eye movement. It consists of two instruments: an optometer to measure the refractive power of the human eye, and an eye tracker. When measuring refractive power, the eye tracker is used to maintain automatically the optical axis of the optometer coincident with the visual axis of the human eye. The measurement range of the optometer is approximately -10 to +10 D; refractive power is measured with an accuracy of about 0.4 D and with a precision of 0.05 D over an eye movement range of 60 degrees. The maximum trackable eye movement velocity is over 100 deg s-1, with a time delay of about 0.13 s. Furthermore it was confirmed that eye refraction measurement during vergence is possible using this eye-tracking infra-red optometer. PMID- 2216480 TI - Anthrax of the eyelid. AB - Anthrax is a rare infection that is transmitted to humans from animals or animal products. In its cutaneous form it may produce lesions of the eyelids which can lead to cicatricization and ectropion. Exophthalmos, optic atrophy and panophthalmitis have also been reported. A case of anthrax affecting the eyelid of a patient seen by the author in Kabul, Afghanistan, is presented. PMID- 2216482 TI - Etymology of the word 'saccade'. PMID- 2216483 TI - The Applied Vision Association: its foundation and early history. The Committee of Management of the AVA. PMID- 2216481 TI - Assessment of surface power and curvature by measurements along meridians at 60, 120 and 180 degrees. PMID- 2216484 TI - Papers presented at the annual meeting of the Applied Vision Association Human Factors in Vision. Manchester, 2-4 April 1990. Abstracts. PMID- 2216485 TI - Tobacco control efforts strong on all fronts. PMID- 2216486 TI - Broadening our horizons. PMID- 2216487 TI - [Current opinions on the endolymphatic sac structure]. AB - There were a lot of discussions about the role of endolymphatic sac in the regulatory mechanism of endolymphatic pressure during the decade 1960-70. Nowadays we know that the balance of metabolism in the inner ear depends on stabilization of fluids in the endolymphatic space. The histologic and anatomic examinations of petrous bone and endolymphatic sac were discussed. PMID- 2216488 TI - [Failures of histopathological verification in malignant tumors of the nasal cavity and paranasal sinuses]. AB - In the years 1966-80, 96 patients with malignant tumors of nasal cavity and paranasal sinuses were operated upon at ENT Department, Medical Academy, Cracow. The frequency of failures in histopathologic confirmation and results of treatment were evaluated. The failures concerned tumors locally advanced. PMID- 2216489 TI - [Histological and electron microscopic examinations of laryngeal papilloma in children and adults]. AB - The authors present the results of histologic and electron microscopic investigations of larynx papillomas in 11 children and 8 adults. Comparative estimation showed the characteristic changes for clinical and morphological division of papilloma into adult-type and juvenile one. Detailed morphological analysis in adult-type papilloma either with dysplastic changes or with hyperkeratosis was performed. PMID- 2216490 TI - [Zinc in the blood serum and tissues in patients with planoepithelial carcinoma of the larynx]. AB - Serum and tissue zinc concentrations in 30 subjects with operable squamous cell carcinoma of the larynx, aged 36-56 were determined by atomic absorption spectrophotometry. The concentration of this cation in cancerous tissues and in unchanged homologous tissues do not differ significantly. Mean zinc serum level was lower before treatment. PMID- 2216491 TI - [Reaction analysis in the oscillating chair test in patients with cerebellar lesions]. AB - The examinations were performed in a group of 53 cerebellar lesion patients. In pendular test the symmetric reaction were in 43, and asymmetrical in 10 patients. There were no symmetrical reactions giving evidence of vestibular hyper-reaction. PMID- 2216492 TI - [Clinical pathology of olfactory neurinomas in the light of current literature]. AB - The modern views on histogenesis of olfactory neurinomas were described. The diagnostic difficulties and importance of ultrastructural and histochemical examinations were stressed. PMID- 2216493 TI - [Incidence and kinds of mycotic infections in the mouth cavity, throat, nasal cavity, maxillary sinus, larynx and ear]. PMID- 2216495 TI - [New outlook on the problem of an anatomic barrier in the lymphatics of the laryngeal mucous membrane]. AB - The authors describe the lymphatic net of the larynx mucosa membrane. The communications of the lymphatic vessels of the larynx and neighbouring organs are analyzed in hypertrophy and atrophy of the mucosa. The experiment performed by means of injections proved that the subglottic area is not a barrier between the two areas of laryngeal mucosa lymphatic system. PMID- 2216494 TI - [Organization of the nasal septum bone and its homologue. II. Os alare et systema palatinum axiale (in fish)]. AB - The aim of these investigations was differentiation and systematization of elements of osseous medial palate and attempt to discover of spheno-orbital bone homologue in fish (os orbito-sphenoideum). 50 adults fish heads of carps, perch , tench , common pikes and trout were examined. The methodology was described elsewhere. It was stated that in examined animals the pair premaxilla was divided into three parts: corps, palate and frontal process. The para-sphenoid bone was also a double biomechanical system, composed of septum homologue and transverse lamina , the same as in other vertebrates. All above mentioned parts create the palatal axial system. The orbital-sphenoidal bones in fishes are homologue to the sphenoidal bone in birds. PMID- 2216497 TI - [Hearing results of cholesteatoma middle ear surgery using open and closed techniques]. AB - The author described an analysis of hearing results in open and closed tympanoplasties of ear cholesteatoma. 172 patients were operated upon. 73 have had open and 99 closed technique. The better hearing results were obtained in closed surgery, but not so good as expected. The unsuccessful hearing results were two times frequent in open surgery. We prefer the two step closed intervention after all pathologic lesions being eradicated. PMID- 2216496 TI - [Administration of prostacyclin in sudden deafness. Evaluation with the double blind method]. AB - Prostacyclin (PGI2) connects all the pharmacologic properties of drugs being used till now in sudden deafness. 30 patients with sensori-neural sudden deafness were treated by prostacyclin and placebo in the double-blind test situation. In therapeutic group of 15 patients were 87% of complete recovery, but in placebo only 6%. PMID- 2216499 TI - [Use of fibrin tissue adhesive in an otolaryngological clinic. Preliminary report]. AB - The tissue glue was used in post-tonsillectomy bleedings, tympanoplasties, cosmetic skin sutures and in prolonged laryngectomy fistulas. The initial evaluation pointed out its usefulness in ENT practice. PMID- 2216498 TI - [Surgical treatment of laryngotracheal stenosis]. AB - In the ENT Clinic, Medical Academy, Cracow a joint ENT team accompanied by thoracic surgeon performed the segmentary resection of trachea in three patients with stenosis of the subglottal area and of the upper section of trachea. The connecting surgery of trachea and thyroid cartilage was successful in two patients, but failed in one. Advantages of this method and reason of failure were thoroughly discussed. PMID- 2216501 TI - [New TNM classification of cancer of the upper respiratory and digestive tracts]. AB - The modified TNM classification of cancers in oral cavity, pharynx, larynx, maxillary sinuses was described. This classification was introduced in 1987 in agreement with UICC and AJCC. The criteria of classification were discussed. PMID- 2216500 TI - [Immunohistochemical examination of olfactory neuroblastoma]. AB - The results of the immunohistochemical examinations by means of PAP method in 3 olfactory neuroblastomas were described. In the neoplastic cells there were cytokeratin as well as neuronal enolase. The same was recently encountered in the merkel cell tumor, which have the analogous histogenesis. The usefulness of the immunohistochemical method of examinations are essential in correct diagnosis. PMID- 2216502 TI - [Computer analysis of the ENG signal in real time]. AB - The theoretical basis of ENG signal analysis in real time was described as well as the equipment and the examination algorithm . 80 ENG examinations were analysed by means of the classical and computer automatic methods. The clinical usefulness of this equipment was presented. PMID- 2216503 TI - [Effect of ethyl ether of apovincaminic acid (Cavinton) on the ototoxic action of sisomicin in guinea pigs]. AB - The aim of this work was to evaluate the protective effect of etyl ether of apovincaminic acid (Cavinton) against the ototoxic effect of sisomycin in the experimental condition. The first group of guinea pigs were given 14 days sisomycin. The second sisomycin and cavinton. The third was the control group. Hearing acuity was tested by the shivering audiometry. The spiral ganglion function was tested by the microphonic potentials and the integrity of cochlea was diagnosed by scanning microscopy. The results pointed out the ototoxicity of sisomycin. There were the deterioration of hearing acuity, lowering of microphonic potentials and degenerative changes in spiral ganglion. The damages were lowered by use of cavinton before the administration of sisomycin. PMID- 2216504 TI - [A case of glomus jugulare chemodectoma]. AB - A case of glomus jugular chemodectoma is described in a 38 years old woman who was treated surgically. In the postoperative course a haemorrhage from the internal carotid artery appeared, needing a second surgical intervention, that was performed with good result. PMID- 2216505 TI - [Unusual pharyngeal foreign body removed by pharyngotomy]. AB - The authors described the unusual pharyngeal foreign body extracted by the lateral pharyngotomy. It was the hoove for the calmars with two wreath of pins. The tracheostomy was difficult, because of the impossibility to lay down the patients. PMID- 2216506 TI - [A case of tuberculosis of the middle ear in a 4-year-old child]. AB - The authors described a rare case of the middle ear tuberculosis in 4 years old child. It was the mastoiditis, which was operated upon. Two years without recurrency in observation. PMID- 2216507 TI - [Organization of the osseous nasal septum and its homologues. III. The sphenoid bone and the vomero-transversal system in Urodela]. AB - In connection with the comparative anatomical examinations of the nasal septum in man, the urodela skulls were examined . The aim of these investigations of the osseous median palatal part and sphenoethmoidal bone were evaluated. 25 skulls of adults frogs were examined. It was stated that parasphenoid in these Amphibians consisted of two parts: agger vomeris and lamina transversalis. These elements were the homologue to the parasphenoideum seu vomero-transversale system in fishes. The premaxilla in frogs belonged (substituted) to the maxillary++ arch. The sphenoethmoidal bone in frogs were the same as the alar bone in birds (part I) and fishes (part II). In all frogs the author did not found any "mesoethmoid ". These precedential facts, observed in birds (I), fishes (II) and amphibians (III) led to further study in mammals and man. PMID- 2216508 TI - [Various forms of mycoses of the oral cavity, pharynx, nasal cavity, paranasal sinuses, larynx and ear]. PMID- 2216510 TI - Insurance nightmare. PMID- 2216509 TI - [Primary cancer of the tongue treated at the Otolaryngological Clinic, Medical Academy, in Poznan 1963-1987]. AB - The analysis of 191 patients with primary tongue carcinoma treated in ENT Clinic of Medical Academy in Poznan during the years 1963-1987 was presented. Since 1983 there were the dramatic increase in patients number. The patients age was between 20 and 87. Statistically significant was the males number. The half of the patients were in their 6th decade of life. In the last 5 years period the patients were younger of mean 5 years. Their symptoms lasted about 4 months. The earliest was the tongue pain. Tobacco smokers and alcoholics predominated. The localizations were in general on the edge and on the basal part of the tongue. Histologically the most frequent was the planoepithelial cancer in the second clinical stage. The 5 years survival rate was about 20%. PMID- 2216511 TI - Generic drug safety challenged. PMID- 2216512 TI - Trustee praises Pittsburgh reporter. PMID- 2216513 TI - Trends in Philadelphia lung cancer mortality rates. PMID- 2216514 TI - Approaching environmental medicine. PMID- 2216515 TI - Can safety belt laws be justified? AB - This article combines the researched sciences of logic, philosophy, and medicine to develop a perspective on safety belt laws. The positions of advocacy and opposition are examined primarily by a nonphysician in a reasonably unbiased manner. The result is an enhanced awareness of principles not commonly employed by physicians which may be useful to the medical profession in dealing with this controversy. PMID- 2216516 TI - Keep income division plan up to date. The Health Care Group. PMID- 2216517 TI - Physicians can meet needs of medical schools. PMID- 2216519 TI - Dr. Redman examines the challenges and issues facing ANA and nursing. PMID- 2216518 TI - Court to rule on settlement of sex discrimination case. PMID- 2216520 TI - There's no quick-fix for success. PMID- 2216522 TI - [Transverse extremity defects in a case of Adams-Oliver syndrome]. AB - Report of a boy aged 15 years with ADAMS-OLIVER-Syndrome, which is associated with dysraphia and cardiomegalia. The differential diagnosis is regarded specially. PMID- 2216521 TI - [Clinical significance of the most important abnormalities of respiratory organs]. AB - The incidence rate and the clinical significance of inborn abnormalities of respiratory organs frequently are still underrated. In the clinic for paediatrics of the Medical Academy of Dresden malformations of respiratory organs, situated below the larynx, were demonstrated in 18 per cent of patients who had been referred hither in the course of 20 years for bronchopulmonary diagnostics. The clinical symptoms are very different and often uncharacteristic. Not seldom malformations of that kind first of all remain silent till a superinfection or a striking roentgenogram will arise the suspicion on a malformation. Following symptoms may refer to: permanent or intermitting stridor in the stenoses of the large respiratory tract (trachea and main bronchi), that is diagnosed as the most frequent anomaly. In nearly 80 per cent of the patients suffering from stenoses of a main bronchus symptoms of a recurrent or chronically obstructive bronchitis stood in the foreground. Mostly a tachy- and a dyspnoe are the leading symptoms in case of a connatal lobar emphysema, the most frequent anmaly of the pulmonary parenchyma followed by the pulmonary hypolasia and -agenesis. Chronic or relapsing pneumonias respectively a persisting cough may appear as symptoms in pulmonary sequestrations and in isolated anomalies of the bronchial aborization that otherwise in the majority of the cases will rest clinically mute. The long term prognosis for children suffering from stenoses in the main bronchis is compared with those of tracheal stenoses relatively satisfactory. PMID- 2216523 TI - [Factor VII deficiency]. PMID- 2216524 TI - [Chlamydia-induced pneumonia in children]. AB - Three cases of pneumonia caused by Chlamydia were observed. The disease ran a protracted course and was refractory to treatment. Erythromycin was given initially intravenously and then orally, with improvement of the general condition of children and regression of inflammatory changes in the lungs. Such cases are worth of reporting in view of only isolated reports on respiratory infections caused by these organisms. PMID- 2216525 TI - [Risk factors of fitness for child day care in 2 independent studies]. AB - The condition of the acute respiratory disease (ARD), conditions of exposure and disposition were found out with 245 and 83 children from 8 creches of a large town and from two creches of a little town. The children were from 6 to 36 months old. The prospective studies were performed independently of each other within a period of one year. Your problem circles were identical to a large extent. These are load factors in the perinatal period, time of stay in the creche, shift work of the parents, kind of the adaptation phase during the first admission in the creche. The employment of the linear function of discrimination found permits the general paediatrician to elaborate an additional information for the judgement of the possibility of attendance into the creche in general and for the time of convalescence after ARD. PMID- 2216526 TI - [Historic, social psychiatric, genetic and anthropologic aspects of turricephaly]. AB - At first estimations of turricephaly from antiquity till modern times are exhibited and at last also results of own examination of over an average disturbed social behaviour and constitutional biological aspects of patients with turricephaly. The dominant inheritance of turricephaly and also peristatic and influences of races in the genesis of premature craniosyntosis are viewed by current literature. PMID- 2216527 TI - [Oculo-auriculo-vertebral dysplasia with abnormal social development]. AB - Report of a 17-year-old boy with oculo-auricolo-vertebral dysplasia. He exhibited microphthalmos on the left and auricular deformity at hemifacial microsomia, scoliosis, dysraphia and other malformations of vertebras and ribs further other minor anomalies of face and hands. The disfiguring microphthalmia with ptosis was an essential cause of a social maldevelopment with temporary important aggressivity. Patients with oculoauriculovertebral dysplasia should be examined for associating cardial and renal dysplasias and cases of psychosocial disorders treated psychotherapeutically in time. PMID- 2216528 TI - [Blood level profile of valproate administration under therapeutic conditions in children]. AB - The antiepileptic drug, valproic acid, was administered to 32 children (valproate calcium 8; valproate plus ethosuximide 10; valproate plus phenobarbitone 2; valproate plus primidone 8; valproate plus DPH, primidone and/or carbamazepine 4). They received valproic acid three times daily (8.00 a.m., at noon, 6.00 p.m.). Valproate blood levels were determined. The study revealed that, in contrast to international recommendations, (i) plasma levels were very high, (ii) unnecessary fluctuations occurred, and (iii) obviously valproic acid was too often administered in combined therapy with other antiepileptics. PMID- 2216529 TI - [Changes in the thyroid status of school children in relation to improved dietary iodine intake]. AB - Five years after the introduction of the iodine prophylaxis examinations on the reaction of the thyroidal state were carried out in 150 children, 9 to 15 years of age in a district of the Erzgebirge in the south of the GDR. The results of the T3-, T4- and TSH-concentrations within the serum demonstrated in all the children an euthyroid metabolic condition. The medium renal iodine elimination of 37.3 +/- 4.7 micrograms iodine/g creatinine still resulted in an ionic deficiency of 2nd degree. The thyroid volumes too measured by sonography and the thyroid masses figured out were significantly more voluminous than those of children of the same age in countries with a sufficient iodine supply since years. The incidence rate of struma in 13-15-year-old children amounted to 21 per cent. The systematic accomplishment of interdisciplinary iodine prophylactic measures will further on be essential during the next years in the GDR. PMID- 2216530 TI - [The experimental transmission of the tick-borne encephalitis virus by ixodid ticks (the mechanisms, time periods, species and sex differences)]. AB - Females and males of ixodid ticks (Ixodes and Dermacentor) infected parenterally with the tick-borne encephalitis virus at the adult or nymphal phase and containing the virus in the saliva are able to transmit the agent in the first minutes after the bite of the sensitive animal host. Preservation of the cement conus produced by saliva in the animal skin enhances the infection intensity because the quantity of the virus in the conus is comparable with that in the tick's body. The virus quantity in the fluid saliva, excreted by I. persulcatus females and measured during different periods of bloodsucking (at least during the first three days), increases 10 to 100 times in comparison with a comparable volume of hungry ones. PMID- 2216531 TI - [The epizootiological significance of flea accumulation in aggregations of the female long-tailed suslik in the Tuva plague focus]. AB - The formation of aggregations of related females is a peculiarity of the intrapopulational organization of long-tailed suslik that results in the accumulation of Citellophilus tesquorum, the main vector and keeper of the plague microbe in the Tuva plague nidus. The plague agent is adapted to the existence on the territory occupied by aggregations of females that manifests itself in the delay of the beginning and prolixity of block-formation periods in fleas. The transfer of the agent from one place to another takes place only at the high abundance of long-tailed suslik. When the number of the suslik is low the plague microbe circulates in the ranges of one or several neighbouring aggregations of females having no possibility for successful transfer to a new place. PMID- 2216533 TI - [Parasite-host relations in toxascariasis in Arctic foxes]. AB - The effect of host infection doze (10, 100, 1000 eggs) and developmental stages of helminths (larvae, adult nematodes) on the relationships in the system "Toxascaris leonina-Alopex lagopus" was studied experimentally. It has been established that 100 eggs are the threshold dose for helminths and 1000 eggs for the host. More distinct changes in the indices are characteristic of the parasite. Dynamics of host-parasite relationships in the development of the parasitic process correspond to helminth developmental stage. Larvae of T. leonina are most pathogenic for the host. PMID- 2216532 TI - [Bound amino acids in local strains of Trichomonas vaginalis]. AB - Amino acid composition of water-soluble and water-insoluble proteins of 8 strains of Tr. vaginalis is studied. 17 amino acids are found in both protein hydrolyzates. Despite the complete coincidence of their qualitative compositions there are reliable differences in the quantitative contents of some amino acids. Differences in the contents of main amino acids of water-soluble proteins of different strains reflect the belonging of the latter to different sero-groups. No reliable differences in the quantitative contents of amino acids of both water soluble and water-insoluble proteins in strains belonging to one sero-group are recognised. PMID- 2216534 TI - Nursing and politics: a profession comes of age. PMID- 2216535 TI - Factors that influence recovery from hip fracture during hospitalization. AB - Fracture of the hip is a major medical problem in the elderly. Of those elderly individuals who are hospitalized for repair of the fracture, only a few will recover and return home. Many will develop chronic disabilities and complications leading to prolonged hospitalization and recovery, and for some, death. This article reviews the literature and identifies positive and negative factors that influence the recovery of the elderly patient with a hip fracture. Nursing interventions to promote recovery are discussed. PMID- 2216536 TI - Crutch walking. AB - This article provides nurses with information on crutch walking which is helpful for patient teaching in a variety of settings. Two nursing diagnoses are discussed: knowledge deficit and potential for injury related to crutch walking. Preparatory exercises and measurement of the patient for crutches are explained, as well as types of weight bearing and point and swing gaits for crutch walking. Crutch maneuvers in and out of a chair or bed, and on stairs are also included. A discharge instruction sheet with tips on crutch walking is provided for use with patients. PMID- 2216537 TI - Clinical support workers: a help or a hindrance to the shortage crisis? PMID- 2216538 TI - Organizing and implementing an Ilizarov program. AB - The Ilizarov external fixator has made a profound impact on orthopaedic science. With its circular design, it allows correction of three-dimensional deformities including rotation, angulation, translation, shortening, and widening, as well as lengthening and soft tissue defects. Because this device is largely patient centered and patient operated, it has presented a new challenge and career investment for the orthopaedic nurse. A comprehensive Ilizarov program is necessary to address the total patient and his multiple needs in any facility where the Ilizarov method of treatment is adopted. The Ilizarov program is a multidisciplinary team approach that provides a structure for administering and providing total patient care for the Ilizarov patient and his significant other(s). PMID- 2216540 TI - An educational program for total hip and knee replacement patients as part of a total arthritis center program. AB - An outpatient and inpatient educational program was developed to meet the medical and surgical needs of arthritis patients undergoing a total hip or knee replacement. This program is one component of a total Arthritis Center Program that includes outpatient treatment, inpatient rehabilitation, and acute medical and joint surgery. The education program consists of five standard classes: Presurgical Total Joint Replacement; What is Arthritis?; Arthritis Medications; Pain, Stress and Coping; and Discharge Total Joint Replacement. The program attempts to prevent complications, decrease anxiety, decrease hospital length of stay, decrease pain, and address the underlying arthritis by preparing patients for the surgery, postsurgery, and discharge. PMID- 2216539 TI - A laser primer for orthopaedic nurses. AB - Laser therapy is an efficient surgical intervention that minimizes tissue manipulation and destruction; however meticulous nursing care is required to safeguard the patient from potential hazards inherent in the procedure. A solid grounding in basic laser concepts including biophysics, correct operation of the equipment, safety, and maintenance will assist the nurse in providing comprehensive, high quality care. The emphasis of nursing practice should be oriented toward comprehensive patient education, psychosocial support, and safeguarding the patient from potential laser hazards. PMID- 2216541 TI - National Association of Orthopaedic Nurses. Chapter presidents' listing 1990 1991. PMID- 2216542 TI - Editing in the 90s. PMID- 2216543 TI - Closed intramedullary femoral shortening. AB - Twelve cases of adult anisomelia were treated with closed intramedullary femoral shortening. Follow-up was conducted at regular intervals until the osteotomy healed. This study reviewed hospital and office records, preoperative and postoperative roentgenograms, and telephone interviews of all patients. An average femoral shortening of 3.7 cm was attained; significant complications such as deep infection or nonunion did not occur. These results suggest that closed intramedullary shortening of the femur produces excellent results in cases of adult anisomelia. PMID- 2216545 TI - Tips of the trade #27. Traction assembly for shoulder arthroscopy. AB - Arthroscopy of the shoulder is facilitated by applying traction to the affected extremity. A sturdy, easily-constructed, and versatile traction assembly is described. PMID- 2216544 TI - Imaging rounds #103. Myositis ossificans in association with congenital radioulnar synostosis and congenital anterior radial head dislocation. AB - Although the initial trauma was minimal in this unusual case of bilateral congenital radioulnar synostosis and anterior radial head dislocation associated with myositis ossificans, a progressive decrease in elbow ROM ensued. Manipulation under general anesthesia was performed to improve flexion and extension of the involved elbow. This manipulation most likely initiated or enhanced the process of myositis ossificans in the elbow. Final treatment consisted of reassurance and active ROM exercises, with resolution of symptoms. PMID- 2216546 TI - Pediatric update #14. Functional rating system for evaluating the results of clubfoot surgery. AB - The results obtained in a study of 32 patients with 45 idiopathic clubfoot deformities treated by complete soft-tissue release between 1985 and 1986 were investigated retrospectively. The evaluation was based on a specifically designed functional rating system. The results were graded as follows: 51% excellent, 25% good, 18% fair, and 6% poor. PMID- 2216547 TI - The real importance of vision/eye screening: "The road to hell is paved with good intentions". PMID- 2216548 TI - A pediatrician's view. PMID- 2216549 TI - Maternal and perinatal issues regarding HIV infection. AB - A review of the information available regarding maternal and fetal factors involved in both protection from and infection with HIV raises more questions than answers. Although providing prevention of HIV infection in women and infants is the ultimate goal, the recent increases in HIV seroprevalence among women of childbearing age gives little hope that this approach will have an effect in the near future. Early detection of HIV infection in pregnant women may provide the opportunity to counsel, provide routine obstetric care, and consider early therapeutic intervention with antiretroviral therapy and active or passive immunotherapy. Identification of HIV-infected infants before they are symptomatic is an equally important goal, as similar therapeutic options may be used. PMID- 2216550 TI - Organ system involvement in HIV-infected children. PMID- 2216551 TI - Pediatric HIV infection. PMID- 2216552 TI - Sports medicine. PMID- 2216553 TI - Psychology of the young athlete. Stress-related maladies and remedial approaches. AB - This article has presented a theoretical framework for understanding the stress process. The conceptual model of stress specifies relations among situational, cognitive, physiologic, and behavioral factors. Each of these basic components of the model is assumed to be influenced by personality and motivational variables. At the situational level, stress involves the balance or imbalance between situational demands and the resources available to deal with them. However, these situational factors affect the person primarily through the intervening influence of cognitive processes. Among the most important of these processes are appraisal of (1) the situational demands, (2) available personal and social resources, (3) the possible consequences of failure to meet the demands, and (4) the perceived meaning of the consequences. A reciprocal relation exists between cognitive and physiologic processes; the nature of the appraisals influences the level of physiologic arousal that is likely to occur, and arousal in turn influences the ongoing appraisal process through physiologic feedback mechanisms. Finally, the behavioral component of the model includes the person's learned behavior tendencies, task-relevant skills, and social skills. Personality and motivational individual difference variables are important; they influence the kinds of situations to which people expose themselves, how they appraise themselves and the situations, how they react physiologically, and how they customarily respond at the behavioral level. With respect to the consequences of stress, mounting evidence suggests that a significant number of young athletes experience adverse psychological, behavioral, and health-related effects. In fact, because of anticipated stresses, some children decline to participate in the first place. Competitive stress detracts from enjoyment of sports, causes performance impairment, and contributes significantly to the drop-out rate in youth sports. Evidence also indicates that competitive stress can cause loss of sleep and put youngsters at greater risk for sustaining athletic injuries. However, although extremely high levels of stress are experienced by a minority of young athletes, the level of stress elicited by youth sports is generally no greater than that found in other achievement-oriented activities in which children participate. The conceptual model of stress not only provides a framework for identifying sources of stress, but also suggests foci for intervention strategies designed to reduce stress in youth sports. In this article, consideration has been given to prominent situational demands that contribute to competitive stress and to various approaches for counteracting the stress-inducing factors. Specifically, measures may be instituted that decrease situational demands associated with winning and losing, organization and administration of sport programs, coaching roles and relationships, and parent roles and responsibilities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2216554 TI - Orthopedic preparticipation screening examination. AB - The primary care physician is often called upon to perform a medical examination before the patient may participate in athletic activities. The examination should identify congenital and acquired musculoskeletal problems and the residuals of previous musculoskeletal injuries. This article and its illustrations show the steps of an orthopedic preparticipation screening examination and indicate how some problems may be identified. PMID- 2216555 TI - Body composition in adolescent athletes. AB - This article has set out to provide basic knowledge about body composition in athletic and nonathletic adolescents and young adults and to provide the practicing physician with methods of making body composition assessment. We suggest the physician approach the adolescent athlete who requests information about body composition in the following way: 1. Calculate the ideal body weight. 2. Estimate the percentage of body fat, realizing the errors associated with each method. If a body composition laboratory is available, use that equipment. In the absence of this equipment, we recommend the equations of Slaughter et al, given earlier. 3. The athlete should be given a range of percentage of body fat values measured in other athletes of the same gender and sport. Health and performance should be monitored as the athlete attempts to achieve or maintain body composition in this range. 4. If the athlete has an interest in altering body composition, then recommend the athlete seek the advice of a professional who has expertise in nutrition and physiology. PMID- 2216556 TI - Heat illness. Fluid and electrolyte issues for pediatric and adolescent athletes. AB - The primary mechanism for maintaining normal body temperature during physical exercise in the heat is the evaporation of sweat. With profuse sweating, water loss far exceeds electrolyte loss. Rigorous exercise in the heat places the athlete at risk for thermoregulatory dysfunction from dehydration. Because children are inherently less efficient thermoregulators than adults, they are at even greater risk for heat illness. The three primary syndromes of heat illness are heat cramps, heat exhaustion, and heat stroke. Treatment of heat illness is based on reduction of body temperature and rehydration. Heat stroke is a true medical emergency with a high mortality rate; immediate reduction of body temperature is critical to the survival of these patients. Prevention of heat illness is based on reducing known risk factors. Physical activity should be modified in the face of high ambient temperature and humidity. The athlete should begin exercise well hydrated; frequent consumption of cold water during exercise decreases likelihood of significant dehydration. After exercise, the athlete should continue drinking to replace fluid losses. Clothing should be lightweight; the more skin exposed, the greater the available evaporative surface. A preseason conditioning program, when combined with an 8- to 14-day period of acclimatization, further reduces the risk of heat injury. Although athletes engaged in endurance sports may benefit from drinking carbohydrate/electrolyte containing solutions, for the majority of young athletes, cold water remains the preferred choice for fluid replacement during exercise. The relatively greater body surface area of young athletes also places them at risk for hypothermia. Special attention should be given when these athletes are competing under cold environmental conditions. PMID- 2216557 TI - Anabolic steroid use in adolescent athletes. AB - Anabolic steroids are being used by adolescents largely to improve athletic performance but also to improve their appearance and to obtain peer approval. With the appropriate knowledge about the effects and side effects of anabolic steroids, primary care physicians can adequately educate teenagers, parents, teachers, and coaches about them and can screen for steroid use, if necessary. PMID- 2216558 TI - Amenorrhea, osteopenia, and the female athlete. AB - Athletic amenorrhea is a problem because it is associated with an increased risk of injuries and potentially an increased risk of osteoporosis in later life. This article gives suggestions for the evaluation of the athlete with amenorrhea and for treatment protocols. Primary care physicians should routinely screen female adolescent athletes for amenorrhea and, if athletic amenorrhea is present, initiate treatment or referral for treatment for this important problem with short- and long-term complications. PMID- 2216559 TI - Nutritional intake in adolescent athletes. AB - Nutrition plays a critical role in the success of the competitive adolescent athlete. Some groups have stricter nutrition requirements than others. The authors summarize nutrition intake data on serious female gymnasts, ballet dancers, and high-school cross-country runners. This article also discusses the nutritional needs of young male wrestlers and weightlifters. PMID- 2216560 TI - Iron deficiency in the young athlete. AB - Although overt anemia is uncommon, depletion of body iron stores is common among adolescent female athletes. Poor dietary iron intake, menstruation, and increased iron losses associated with physical training all appear to be important factors. Whether nonanemic iron deficiency can impair exercise performance is uncertain. Nonetheless, athletes with low ferritin levels are at risk for impaired erythropoiesis and should receive therapeutic iron supplementation. PMID- 2216561 TI - A review of the use of prophylactic knee braces in football. AB - A review of nine studies of prophylactic knee braces worn by players in American tackle football lends some support for the use of double-hinged braces at the high-school level. Evidence for their use at the college level seems less persuasive. Caution should be exercised in interpreting these studies owing to the probable presence of bias and confounding variables and to difficulty in generalizing results beyond the study populations. The two studies that assigned braces randomly found lower injury rates for knees and knee ligaments among high school and high-school size players. Conversely, a large, multiteam collegiate study found a significantly higher rate of knee injuries among brace users, a difference that remained when controlled for position, skill, and previous injury. PMID- 2216562 TI - Strength training in children and adolescents. AB - Strength is the ability to exert muscular force against resistance. It is a fundamental requirement of most daily physical activities of children and of adults. Strength training is the use of progressive resistance exercise methods specifically to increase strength. Strength training for children and adolescents is not without risk. Proven medical concerns relate to back, shoulder, and other joint injuries and to hypertension and related diseases. However, the rate of injury is probably rather low, comparable to many youthful activities that are considered safe. Also, the incidence and severity of injury can probably be minimized by adherence to the guidelines presented. Children may be expected to become stronger with appropriate training. Increased strength can enhance their performance in those athletic activities in which strength, power, or speed are required. It may reduce the incidence and severity of overuse injury in sport. However, it cannot reasonably be expected to protect against serious, acute injury in sport. PMID- 2216563 TI - The child dancer. Medical considerations. AB - Ballet training is associated with various injuries in children, most of them overuse injuries. Errors in technique and abrupt changes in training are the most frequent causes of injury. Forcing turn-out is the most common technique error. The author presents background information about ballet training to help primary care physicians treat dancers and advise their parents. PMID- 2216564 TI - Education: first to get called, first to get axed. PMID- 2216565 TI - Changing patterns in offering solids to infants. AB - Factors influencing changing patterns in introducing nonmilk foods (beikost) to infants are reviewed. Currently, developmental readiness based on individual needs is favored. Caregivers may receive conflicting advice from women who cared for infants when very early introduction of beikost was widely practiced. PMID- 2216566 TI - Formula feeding in the first year of life. AB - Over 60% of all infants in the United States are completely formula-fed by 2 months of age. A nursing diagnosis framework can aid nurses in supporting and guiding parents who formula-feed their infants. PMID- 2216568 TI - Accurate assessment of infant emesis volume. AB - When infants vomit, hospital nurses sometimes record these volumes in ccs. Fluid replacement is often based on these estimates. A review of the literature indicates that this subjective assessment is highly problematic. PMID- 2216567 TI - Sleep disturbances of the infant and toddler. AB - Two common sleep disorders of the infant and toddler stages of development are sleeplessness and arousal disorders. Effective methods are available to reduce the impact of these problems upon the family. PMID- 2216570 TI - Pediatric emergency review: a "hands-on" approach. AB - A "hands-on" approach to pediatric emergency review was developed to improve retention of psychomotor skills and instill critical thinking for pediatric nurses in anticipation of pediatric emergency situations. PMID- 2216569 TI - Concerns of mothers of low birthweight infants. AB - To provide more comprehensive follow-up care for low birthweight infants, it is important for nurses to know what concerns mothers of these low birthweight infants commonly experience and how concerns change over time. This descriptive, longitudinal study followed 65 mothers of low birthweight infants from birth until the infant was 6 months adjusted gestational age. Most concerns were raised the week following birth (109) and after infant discharge (72), although from 40 weeks (62) to 6 months (40), the number of concerns raised were fairly consistent. The largest category of concerns was health related (253). PMID- 2216572 TI - What is EPO? PMID- 2216571 TI - Parenting growing preterm infants. AB - A convenience sample of 24 parents of growing preterm infants reported concerns related to their preterms' health and development, parenting abilities, family relationships, and finances. PMID- 2216573 TI - Retrovir approved for use in children. PMID- 2216574 TI - Develop your thinking skills for improved test taking. PMID- 2216575 TI - Comparison of therapeutic touch and casual touch in stress reduction of hospitalized children. AB - PURPOSE: To compare the effectiveness of therapeutic touch and causal touch for stress reduction of hospitalized children aged 2 weeks to 2 years old. METHODOLOGY: Stress reduction was measured by pulse, peripheral skin temperature, and galvanic skin response as observed on the GSR-II biofeedback instrument. RESULTS: An ANOVA measured effectiveness of the interventions of causal touch and therapeutic touch at 3 and 6 minute intervals. The results demonstrated a significant difference with the critical value of F = 4.18 p less than .05. The computed value of F = 26.98 at 3 minutes and F = 26.94 at 6 minutes. CONCLUSION: Therapeutic touch reduced time needed to calm children after stressful experiences. PMID- 2216577 TI - The Family Support Act: a potential for promoting the development of poor children. PMID- 2216578 TI - Pediatric management problem. Hand-foot-and-mouth disease. PMID- 2216576 TI - Maintaining the artificial airway: current concepts. AB - Artificial airways are a common treatment modality in neonatal and pediatric critical care units. Maintaining the integrity of artificial airways in infants and children requires accurate assessment of endotracheal tube (ETT) position and patency, adequacy of oxygenation and ventilation, and the identification and treatment of potential complications. PMID- 2216579 TI - Using videorecordings in pediatric nursing practice. AB - This article explores the innovative uses of videorecordings in pediatric nursing practice. Social learning theory and primary nursing concepts provide the conceptual orientation. Creative uses of videorecordings include: enhanced family education; continuity of care through caregiver modeling and staff communication; audiovisual progress recording; and potential behavioral development in the pediatric client. Suggestions regarding technical aspects of videorecordings in the clinical area may facilitate videorecording application. PMID- 2216581 TI - Using time effectively. AB - Managing your own time effectively is perhaps one of the most challenging responsibilities a nurse manager faces. This article describes several strategies to assist in time management for busy nurse managers. PMID- 2216580 TI - Cardiovascular screening programs: implications for school nurses. AB - Programs directed toward the identification, prevention, and intervention of blood pressure variations in children and their implications for school nurses are detailed. PMID- 2216582 TI - Diagnostic value of ultrasound in children with recurrent abdominal pain. AB - In order to investigate the diagnostic value of ultrasound in children with recurrent abdominal pain and to estimate the clinical relevance of rare organic causes of abdominal pain in these patients, we prospectively examined 93 children aged between 5.5 and 12 years by means of abdominal ultrasound. In 3 patients (3.2%) an anatomic abnormality was detected, which could not account for the abdominal pain. We conclude that many organic abnormalities, that could be diagnosed by ultrasound, are clinically irrelevant as a cause of recurrent abdominal pain in children and therefore ultrasound does not significantly contribute to the diagnosis. However, ultrasound can still play a role in the work-up of children with recurrent abdominal pain in avoiding unnecessary radiologic X-ray procedures. PMID- 2216583 TI - Dopplersonographic classification of brain edema in infants. AB - 25 infants, 23 newborns and 2 older infants with B-mode sonographic evidence of cerebral edema (gestational age of the newborns 39.1 +/- 2.1 weeks, weight 3270 +/- 672 g) were examined by means of pulsed Doppler sonography. Pulsed Doppler recordings were obtained in the anterior cerebral, internal carotid, basilar, and middle cerebral arteries. In all measured arteries the peak systolic peak endsystolic, peak enddiastolic and the time averaged mean velocities, as well as the resistance index and the pulsatility index were determined. In addition to the flow parameters the pH, pCO2, pO2, oxygen saturation and the blood pressure were measured. The flow velocities were compared with the normal values established by our group. Three different types of flow profiles and velocities could be found: Group 1: 12 infants had normal flow velocities. Group 2: 7 infants showed increased diastolic flow velocities. Group 3: 6 infants demonstrated decreased diastolic flow velocities. There were no significant differences according to gestational age, weight, pH, pCO2, pO2, oxygen saturation and blood pressure in the three groups. The outcome of the 12 children in group 1 was favourable: normal development 10; minor retardation 2. In group 2 only 1 child showed normal development; 2 infants had minor, 1 major handicaps; 2 infants died. Patients in group 3 had the worst outcome: no patient developed normally; 4 infants died; 2 severely handicapped infants showed polycystic leucomalacia and brain atrophy; 1 infant had minor psychomotoric problems. PMID- 2216585 TI - Coronary artery calcification in Kawasaki disease. AB - To evaluate the angiographic features of coronary lesions in Kawasaki disease with coronary artery calcification, cinefluoroscopy and cineangiography were retrospectively reviewed in 116 patients who had undergone coronary angiography between 1982 and 1989. Angiographic abnormalities of coronary arteries were demonstrated in 55 of the 116 patients. In 5 (9.1%) of the 55 patients, 9 with calcification were identified by cinefluoroscopy and chest x-ray. Eight of the 9 calcified lesions showed a circular or ring-shape configuration. Coronary angiography revealed a total occlusion of the right coronary artery with collateral circulation from the distal left coronary artery in 2 patients and a severe stenosis of the right coronary artery in 2 patients, in whom anticoagulant therapy had not been continued during the follow-up periods. The remaining patient in whom anticoagulant therapy had been continued had bilateral aneurysms but no significant stenosis. These results indicate that a ring-shape calcification on chest x-ray in a patient with a history of Kawasaki disease may suggest an involvement by coronary artery stenosis even when anticoagulant drugs had been given. Therefore, coronary angiography should be performed to evaluate the stenotic lesions if this type of calcification is found by routine radiographic examination. PMID- 2216584 TI - Comparison of plain and Gd-DTPA-enhanced MR-imaging in children. AB - 40 children and adolescents (aged 1-16 years) were examined by MRI at 1.0 T. Gd DTPA was given intravenously at a dose of 0.1 mmol/kg body weight. In all cases T1-weighted SE sequences were used to demonstrate contrast enhancement. No adverse effects were seen. 30 patients had one or more lesions; in 20 patients contrast enhancement was seen. In 4 cases lesions were not observed by plain MRI and could only be detected after Gd-DTPA. In addition, contrast enhancement provided additional information about the differentiation of lesion from edema or necrosis in 13 patients. Normal brain matter did not show any changes in signal intensity. However, an age-dependent signal increase was found in the normal vertebral bone marrow in all children. Gd-DTPA should be used as a supplementary examination whenever a tumor or an infectious disease of the CNS is suspected and plain MRI is normal, or when origin and extent of a lesion cannot be adequately defined with plain MRI. PMID- 2216586 TI - Esophageal perforation with mediastinal abscess in child abuse. AB - A case of mediastinitis and mediastinal abscess due to cervical esophageal perforation in a 9/12 month old girl who was a victim of child abuse and possible sexual assault is reported. Injury to the hypopharynx or esophagus with child abuse as a possible etiology should be considered when an infant or young child presents with unexplained erythematous neck swelling, subcutaneous emphysema, pneumomediastinum and/or wide mediastinum. PMID- 2216587 TI - Gastric trichobezoars--sonographic and computed tomographic appearance. AB - We report two young girls with gastric trichobezoars in whom ultrasound, computed tomography and upper gastrointestinal contrast studies were done. Since sonography and, less frequently, computed tomography are usually the first studies obtained in a child with an abdominal mass it is important to recognize the rather distinctive appearance of a trichobezoar on these images. PMID- 2216589 TI - MR imaging of pancreas in cystic fibrosis. AB - The pancreatic regions of 18 patients with cystic fibrosis were analyzed with a 1.5 Tesla MR unit. Signal intensity of the pancreas was correlated with clinical data and ultrasound. A hyperintense pancreas on T1-weighted image was consistent with fatty replacement of pancreatic insufficiency. A pancreas of normal soft tissue intensity was found in two asymptomatic and one symptomatic patient. A very hypointense pancreas on any pulse sequence was considered to be an intermediate stage of pancreatic degeneration. PMID- 2216590 TI - Urinoma formation in posterior urethral valves: relationship to later renal function. AB - A retrospective analysis of radiologically determined individual renal function was performed in five boys who presented in the neonatal period with posterior urethral valves, vesicoureteral reflux and documented urinoma formation. Renal function was evaluated with scintigraphy. There was reflux in eight of ten ureters. Six of these ureters had an associated urinoma and compromised renal function in the neonatal period. In two of the boys the kidney with urinoma functioned better than the contralateral kidney with reflux alone. In two other boys with unilateral urinoma the contralateral ureter did not reflux and the affected kidney functioned less well. In follow up (20 to 36 months) seven of the ten kidneys have a near normal appearance or function. Those kidneys which are now abnormal were noted to be abnormal in the neonatal period. PMID- 2216588 TI - Foetal hepatic calcification. AB - Thirty-three cases of 1,500 spontaneously-aborted foetuses showed hepatic calcifications. The exact location of these calcifications were confirmed by contrast studies, anatomic dissection, and further histology when necessary. Of them, 18 were calcified hepatic vein thrombi (CHVT), 12 were calcified portal vein thrombi (CPVT), 2 were parenchymal calcifications, and one was mixed. Associated anomalies were high (85% of cases). No significant difference was found between the type and percentage of anomalies of those with CHVT and those with CPVT. The most common anomalies encountered in all cases were meconium intraluminal calcification (27%), cystic hygroma (18%), and metaphyseal defect (18%). In view of this, it is suggested that a variety of severe foetal illnesses predispose to CHVT and CPVT. At correlation with maternal factors, it was found that the highest incidence was in the third decade. A significant high percentage of mothers (33%) had been on contraceptive pills, and there was interesting inverse relationship of hepatic calcification with gravidity. Practically, it is also hoped that the awareness of the presence of various types of hepatic calcifications will help in their detection prenatally by ultrasound. PMID- 2216591 TI - Eosinophilic granuloma of the temporal bone: radiological approach in the pediatric patient. AB - Eosinophilic granuloma is one of the three clinical variants of Histiocytosis-X (eosinophilic granuloma, Hand-Schuller-Christian and Letterer-Siwe disease). Involvement of the temporal bone is relatively rare and initially silent. However, it can erode the mastoid cortex, destroy the tegmen and extend into the cranial vault, as well as erode the semicircular canals or cochlea. It usually presents as an aural polyp or postauricular swelling. Chronic otorrhea is what brings the patient to the ORL-Clinic. It is frequently confused with infectious diseases or neoplastic conditions of the temporal bone. In this paper we report 6 cases of eosinophilic granuloma in the temporal bone, discuss the plain radiological and CT findings and review the literature. PMID- 2216592 TI - MR and ultrasound findings in a case of cerebro-oculo-muscular-syndrome. AB - We report on a boy with type II lissencephaly and congenital muscular dystrophy. The patient presented with the features of a cerebro-oculo-muscular syndrome (COMS). We describe the clinical presentations and the characteristic sonographic and MR findings. PMID- 2216593 TI - MRI of mediastinal cavernous hemangioma. AB - A cavernous hemangioma of the anterior mediastinum was studied by CT and MRI. CT did not give the diagnosis of the vascular tumor but MRI demonstrated the morphology of the vascular tumor. MRI is very useful for detecting a vascular tumor in the mediastinum. PMID- 2216594 TI - CT of an actively-hemorrhaging liver laceration in a 9-year-old child. AB - A 9-year-old female with blunt abdominal trauma following a motor vehicle accident was referred from the Emergency Room for abdominal CT imaging. CT demonstrated the unusual and heretofore unreported finding of an actively hemorrhaging liver laceration. PMID- 2216595 TI - Pseudoascites: unusual presentation of omental cyst. AB - An unusual case of omental cyst is described. The child initially presented with a unilocular intraperitoneal fluid collection on CT. After paracentesis, CT showed freely layering peritoneal fluid, with eventual complete resolution of fluid. CT eight months later demonstrated re-appearance of a multi-septated cystic mass. At surgery, an omental cyst was found. PMID- 2216596 TI - Rhabdoid tumor of the kidney presenting as an abdominal mass in a newborn. AB - Rhabdoid tumor of the kidney is a highly malignant tumor seen in the neonatal population with a characteristic clinical course. There are no known radiologic features to differentiate rhabdoid tumor of the kidney from other renal tumors; however, this report presents a newborn infant with rhabdoid tumor of the kidney who had a normal prenatal ultrasound at ten days prior to birth, followed by an abnormal prenatal ultrasound one day prior to birth. Observation of such a rapid development of a tumor in the kidney in a fetus or an infant should raise the possibility of a highly malignant tumor such as a rhabdoid tumor. PMID- 2216597 TI - Unusual radiographic presentation of IgA nephropathy. AB - An adolescent male presented with hematuria and flank pain. Transient focal renal parenchymal defects were demonstrated by ultrasonography, radionuclide scintigraphy and computed tomography. Renal biopsy revealed IgA nephropathy with acute tubular necrosis. This peculiar radiographic pattern has not, to our knowledge, been previously described in IgA nephropathy and may relate to tubule cell damage by red blood cell casts or patchy renal ischemia. PMID- 2216598 TI - Sonographically detected costo-chondral dislocation in an abused child. A new sonographic sign to the radiological spectrum of child abuse. AB - A case of an abused child with fractures of the skull, ribs and long bones is presented. Sonographically a costochondral dislocation of the left lower ribs was detected, which has not been reported in the literature. PMID- 2216599 TI - The Hajdu-Cheney syndrome: a case report and review of the literature. AB - Hajdu-Cheney syndrome which is also known as type VI idiopathic osteolysis is a rare disease transmitted autosomal dominantly. In this syndrome, osteolysis involves primarily the terminal phalanges. We describe here a 18-year-old boy with typical clinical and radiological signs of Hajdu-Cheney syndrome. PMID- 2216601 TI - Physeal and epiphyseal involvement in chronic recurrent multifocal osteomyelitis (CRMO) PMID- 2216600 TI - Intrauterine dwarfism, peculiar facies and thin bones with multiple fractures--a new syndrome. PMID- 2216602 TI - IGG subclass deficiency: fact or fiction? Proceedings of a workshop. Sydney, New Wales, Australia. PMID- 2216603 TI - IgG subclass distribution of antibodies to bacterial and viral antigens. PMID- 2216604 TI - T cell regulation of immunoglobulin isotypes in health and disease. PMID- 2216605 TI - IgG subclass deficiency: a personal viewpoint. PMID- 2216606 TI - IgG subclass concentrations in absolute, partial and transient IgA deficiency in childhood. AB - Sixty-seven children with symptomatic IgA deficiency were studied on two separate occasions. Eighteen had aIgAd at presentation, and 49 had pIgAd. IgA concentrations had risen to the normal range for age in 22.2% of children presenting with aIgAd and 77.6% presenting with pIgAd when restudied at a median interval of 3.2 and 3.0 years, respectively. IgG subclass concentrations were measured by enzyme immunoassay in serum samples collected at enrollment from 12 children with aIgAd and 22 children with pIgAd. IgG2 and IgG4 concentrations for these 34 children were below the 5th centile for age and sex more frequently than expected (IgG2: chi square 5.8, P less than 0.025; IgG 4: chi square 18.4, P less than 0.0005). The prevalence of IgG2 deficiency or IgG4 deficiency did not differ significantly between those with aIgAd and those with pIgAd. IgG2 concentrations remained below the 5th centile more frequently than expected when retested in 31 children whose pIgAd had resolved (chi square 4.6, P less than 0.05). Children with aIgAd at presentation had IgG1 and IgG2 concentrations above the 95th centile more frequently than expected (IgG1: chi square 19.7, P less than 0.0005; IgG2: chi square 13.5, P less than 0.001) but this was not seen for IgG3 and IgG4 concentrations. Children with pIgAd did not have elevated IgG1 or IgG2 concentrations at presentation. High IgG1 and IgG2 concentrations in aIgAd may be a compensatory mechanism to afford protection from infection or could be part of a selective secondary response to repeated episodes of infection. PMID- 2216607 TI - IgG subclasses in acquired immunodeficiency. PMID- 2216608 TI - Immunoglobulin subclass abnormalities in patients with chronic fatigue syndrome. PMID- 2216609 TI - Aspects of immunoglobulin replacement therapy. AB - Immunoglobulin replacement therapy appears to benefit some patients who have IgG subclass deficiencies. Because some patients with subnormal trough concentrations of IgG subclasses remain well, because other patients who have borderline/low normal concentrations of an IgG subclass are abnormally infection-prone and helped by immunoglobulin therapy and because infection proneness in individual patients does not always appear to parallel their IgG subclass concentrations, it is evident that IgG subclass concentrations, while a helpful guide, are not an absolute determinant of the need for immunoglobulin replacement therapy in infection-prone patients. Low IgG subclass concentrations may indicate impaired ability to produce certain "specific" antibodies and antibody replacement is likely to be the crucial factor in treatment rather than merely maintaining concentrations of IgG subclasses at particular levels. PMID- 2216610 TI - Percentile ranges for IgG subclass concentrations in healthy Australian children. PMID- 2216611 TI - Initial evaluation of heart murmurs: are laboratory tests necessary? AB - Heart murmurs, most of them innocent, are the most common reason for referrals to a pediatric cardiologist. In the evaluation of murmurs, the electrocardiogram and echocardiogram are often included. The purpose of this study was to determine the utility of these examinations in the initial assessment of heart murmurs in children and adolescents. In a prospective series of 161 patients, the clinical diagnosis of heart murmurs by a pediatric cardiologist was compared with that obtained after electrocardiogram and echocardiogram (two-dimensional, M-mode, Doppler, and color-Doppler). On the basis of the clinical diagnosis the patients were classified as having "innocent murmur," "pathologic murmur," or "possible pathologic murmur." A total of 161 patients (51% males), aged 1 month to 17 years (median 3.2 years), were studied. After electrocardiogram, no diagnosis was changed. After echocardiogram, the clinical diagnosis of innocent murmur in 109 patients changed in 2 to pathologic (small ventricular septal defect 1, small atrial septal defect 1); pathologic murmur in 46 changed to innocent in 3 and possible pathologic in 2; and possible pathologic in 6 changed to innocent in 3 and to pathologic in 2. The clinical examination by an experienced pediatric cardiologist is an accurate means of assessing newly referred patients with murmurs. The clinical examination had a sensitivity of 96%, specificity of 95%, positive predictive value of 88%, and negative predictive value of 98%. The electrocardiogram, unlikely to disclose any unsuspected heart disease, may assist in reaching the lesion-specific diagnosis when there is underlying pathology. Echocardiography, although diagnostic when heart disease is suspected, is unnecessary in pediatric patients with clinically diagnosed innocent heart murmurs. PMID- 2216612 TI - Phenobarbital and cerebral blood flow during hypertension in the newborn beagle. AB - Phenobarbital sodium has been used in anticonvulsant concentrations (15 to 40 micrograms/mL serum) in premature newborns in attempts to prevent periventricular and intraventricular hemorrhages. Although its clinical usefulness in this regard is controversial, phenobarbital treatment has been shown to reduce periventricular and intraventricular hemorrhages after hypertensive insult in newborn beagles. In this study cerebral blood flow values in steady state and during phenylephrine-induced hypertension with and without phenobarbital pretreatment were measured in newborn beagles. At anticonvulsant dosage, phenobarbital sodium decreased mean arterial blood pressure transiently during steady state and significantly reduced total cerebral blood flow during phenylephrine-induced hypertension without reducing mean arterial blood pressure. This phenobarbital sodium effect on cerebral blood flow was not as great in the presence of acidosis, and the initial hypotensive effect of phenobarbital sodium was sustained for a longer period of time during acidosis. Phenobarbital sodium may reduce the incidence of hemorrhages in the newborn brain by providing protection against isolated hemodynamic stresses characterized by acute increases in cerebral blood flow, with or without increased mean arterial blood pressure. PMID- 2216613 TI - Nebulized albuterol in acute childhood asthma: comparison of two doses. AB - Thirty-three children and adolescents from 5 to 17 years of age with moderate to severe acute asthma were given nebulized albuterol therapy in either a high (0.30 mg/kg body weight) or standard (0.15 mg/kg) dose administered at three hourly intervals in a randomized double-blind study. The high-dose hourly regimen resulted in significantly greater improvement in the forced expiratory volume in 1 second (FEV1). Furthermore, patients receiving the high dose showed a steady improvement in the FEV1 from the start to the end of the study, whereas FEV1 plateaued after the second dose in the standard-dose group. Although a rise in heart rate and a fall in serum potassium level occurred, neither of these changes nor other side effects were different in the two groups. The high-dose therapy resulted in much higher serum albuterol levels than the standard dose. There was no correlation between the drug levels and side effects or initial and subsequent FEV1. It is concluded that occasional hourly high-dose albuterol therapy should be considered for some pediatric patients with acute asthma of moderate severity, especially those who relapse between doses. PMID- 2216614 TI - The UCLA-University of Utah epidemiologic survey of autism: prenatal, perinatal, and postnatal factors. AB - In a recent epidemiologic survey conducted in Utah, 241 autistic patients (DSM III criteria) were found. Medical records of 233 autistics were surveyed for the presence of 36 potentially pathologic prenatal, perinatal, and postnatal factors. These results were compared with those of an identical survey of 62 of their nonautistic siblings, with the results of four previously published surveys, and with normative data. No potentially pathologic factor or group of factors occurred significantly more frequently among the autistic patients. Also, previous observations of significant differences in the occurrence of certain factors in the histories single vs multiple siblings with autism were not confirmed, with the exception of increased viral-type illness during gestation in single-incidence cases. Thus, the etiology of the brain pathology that characteristically disrupts normal development and produces the syndrome of autism remains obscure. Other data from the epidemiologic survey, however, suggest that the role of genetic factors needs to be explored further. PMID- 2216615 TI - Intake and food sources of dietary fat among schoolchildren in The Woodlands, Texas. AB - To investigate the nutrient intake and food use patterns among schoolchildren, diet was assessed among 138 children and adolescents in grades 5 through 12 using three random, nonconsecutive, 1-day food records. Mean intake of total fat, saturated fat, and polyunsaturated fat as percent of calories was 35.6%, 13.4%, and 6.6%, respectively. Among all subjects, 17% consumed diets containing less than 30% of calories from fat, 34% consumed greater than or equal to 38% of calories from fat, 7% consumed less than 10% of calories from saturated fatty acids, and greater than 97% ate less than 300 mg of cholesterol per day. While intake of calories, sodium, and beta-carotene per 1000 kcal was higher in subjects consuming higher fat diets, intake of other micronutrients was either higher among those eating low-fat diets or did not differ by level of fat intake. Differences were seen in the amount of saturated fat and cholesterol that individual food sources contributed to the diets of subjects eating high and low fat diets. These cross-sectional data show that a substantial proportion of children and adolescents in this population are consuming diets low in fat and cholesterol without systematic differences in intake of other nutrients, suggesting that current dietary guidelines regarding fat intake are attainable within the current food use pattern of healthy, school-aged children and adolescents. PMID- 2216616 TI - Safety and immunogenicity of Haemophilus influenzae type b oligosaccharide-CRM197 conjugate vaccine in infants aged 15 to 23 months. AB - A total of 268 infants aged 15 to 23 months received one dose of a vaccine composed of Haemophilus influenzae type b oligosaccharides covalently linked to the nontoxic diphtheria toxin variant CRM197 (HbOC; HibTITER). Side effects associated with vaccination were infrequent, transient, and mild. One month after a single vaccination, the anti-H influenzae type b capsular polysaccharide antibody concentration rose from a geometric mean prevaccination level of 0.20 microgram/mL to 13.77 micrograms/mL. Of these infants, 99% had a postvaccination level greater than or equal to 1.00 microgram/mL, a level associated with long term protection. The immune response was long-lived: all of the children who were monitored 17 to 27 months after vaccination had concentrations greater than or equal to 1.00 microgram/mL. The anti-H influenzae type b capsular polysaccharide antibody generated was predominantly of the IgG isotype and IgG1 subclass. The immune sera had bactericidal activity in vitro and conferred passive protection in the infant rat meningitis model. PMID- 2216617 TI - Dietary protein source and plasma lipid profiles of infants. PMID- 2216618 TI - Chronic fetal hypoxia and sudden infant death syndrome: interaction between maternal smoking and low hematocrit during pregnancy. AB - To investigate the hypothesis that chronic fetal hypoxia contributes to the etiology of sudden infant death syndrome (SIDS), a possible interaction between the effect of maternal cigarette smoking and low hematocrit during pregnancy on the risk of SIDS was studied using the US Collaborative Perinatal Project cohort. The 193 SIDS cases identified in the cohort were analyzed with 1930 controls randomly selected from infants who survived the first year of life. After adjustment for maternal age, infants born to mothers who smoked 10 or more cigarettes per day and who were anemic (hematocrit less than 30%) during pregnancy were at a much higher risk of SIDS than infants born to mothers who did not smoke and were not anemic (odds ratio = 4.0; 95% confidence limits, 2.1 and 7.4). Smoking 10 or more cigarettes per day vs none increased the risk of SIDS by 70% among women with hematocrit at or above 30% but increased risk threefold among women with hematocrit below 30%. After adjustment for more potential confounders in a logistic regression model, the effect of smoking on SIDS continued to increase with lower levels of hematocrit during pregnancy. Birth weight accounted for very little of these associations. Low hematocrit was not a risk factor for SIDS among nonsmokers but became an important predictor among heavy smokers. These findings are in agreement with the hypothesis that chronic fetal hypoxia may predispose to SIDS, possibly by impairing the normal development of the fetal central nervous system. PMID- 2216619 TI - Early solid feeding and recurrent childhood eczema: a 10-year longitudinal study. AB - The relationship between early solid feeding practices and risks of recurrent or chronic eczema in childhood was examined in a birth cohort of New Zealand children studied to the age of 10. By the age of 10 years, 7.5% of children had chronic or recurrent eczema. There were clear and consistent associations between the diversity of the child's diet during the first 4 months and risks of eczema. Even when due allowance was made for a range of confounding factors--including parental atopic illness, atopic illness in siblings, the child's early milk diet, and family social background--children exposed to four or more different types of solid food before 4 months had risks of recurrent or chronic eczema that were 2.9 times those of children who were not exposed to early solid feeding. It is concluded that early exposure to a diet diverse in potential food antigens may act to predispose susceptible children to recurrent or chronic childhood eczema. PMID- 2216620 TI - Substance abuse education in pediatrics. AB - Historically, physicians have received little formal education related to alcohol or other drug abuse and dependence. A survey of all pediatric programs in the United States was conducted to assess the current status of alcohol/drug education in pediatrics. At the medical student and residency training levels, only 44% and 40% of programs, respectively, required any formal instruction, and only 27% and 34%, respectively, offered an elective for medical students or residents. Although most respondents endorsed the inclusion of both required and elective alcohol and drug education in the curriculum, few programs that did not include it already had a future plan for it. Major impediments identified were curriculum time constraints (86% medical student level, 68% resident level) and the lack of a qualified instructor (55% medical student level, 50% resident level). The survey results suggest a strong need for development of faculty and structured alcohol and drug abuse educational plans specific to pediatrics. PMID- 2216621 TI - Open lung biopsy in the critically ill newborn. AB - Experience with 17 open lung biopsies in critically ill premature neonates was reviewed. Despite their small size, prematurity, and near maximal ventilator requirements, the infants suffered no significant complications. In three cases, an infectious agent was identified. In one case end-stage lung fibrosis associated with persistent (greater than 3 months), severe respiratory failure prompted termination of support. In the remainder of the cases, definitively ruling out infection allowed the confident trial of a course of steroids in an attempt to treat bronchopulmonary dysplasia. Unlike older patients, the definitive diagnosis of no infection in the premature neonate is just as informative as the diagnosis of an infection. Used judiciously, open lung biopsy can be performed in the premature infant with acceptable morbidity and mortality. PMID- 2216622 TI - Single- versus multiple-dose surfactant replacement therapy in neonates of 30 to 36 weeks' gestation with respiratory distress syndrome. AB - To assess the efficacy of a multiple-dose protocol of surfactant replacement therapy in neonates of 30 to 36 weeks' gestation, 75 neonates were randomly assigned to control, single-dose surfactant, or multiple-dose surfactant groups. Neonates at less than 6 hours of age with a diagnosis of respiratory distress syndrome were eligible. Subjects were randomly assigned to receive either 100 mg/kg of bovine surfactant or air placebo. Neonates in the multiple-dose group were eligible to receive up to three additional doses as indicated. Neonates in both surfactant groups showed a positive response to treatment, with marked improvement in oxygenation by 10 minutes postinstillation (P less than .0001). Both surfactant groups had better oxygenation than control subjects at lower ventilatory parameters over the first 24 hours. A deterioration in oxygenation and ventilatory requirements was seen in both treatment groups starting 6 to 12 hours after the first dose. The deterioration in oxygenation could be minimized by the use of multiple doses; however, extra doses had no effect on diminishing ventilatory requirements or time to extubation. It is concluded that surfactant therapy at less than 6 hours of age is effective in acutely reducing oxygen and ventilatory requirements in neonates of 30 to 36 weeks' gestation with respiratory distress syndrome. It appears that multiple doses of surfactant have a greater effect on sustaining improvements in oxygenation than on ventilatory requirements. Further study is required to determine optimal dosage and retreatment strategy. PMID- 2216623 TI - Vancomycin-induced red man syndrome. AB - A total of 11 cases of red man syndrome collected among 650 children who had received vancomycin in our hospital between 1986 and 1988 (estimated prevalence 1.6%) were retrospectively analyzed. These 11 children were compared with 11 age matched children who received vancomycin in whom red man syndrome did not develop. Of the patients with red man syndrome, 73%, and of the patients with no reaction, 45.4% received vancomycin for penicillin-resistant Staphylococcus epidermidis-positive cultures, or because of history of penicillin allergy. No difference was observed in the dose per kilogram given to both groups (12.9 +/- 3.5 mg/kg per dose in those with red man syndrome vs 12.3 +/- 6.9 mg/kg per dose in control children. The duration (mean +/- standard deviation) of vancomycin infusion was 45.9 +/- 16.7 minutes (range 10 to 90 minutes) in patients with red man syndrome and 54.5 +/- 7.6 minutes (range 45 to 65 minutes) in the control group (P = .07). In the 5 children with red man syndrome rechallenged with vancomycin, slower infusion rates prevented or reduced the syndrome, which emphasized the fact that the rate of administration is the important determinant of red man syndrome in susceptible cases. Clinically, the syndrome developed at the end of the infusion in most patients, but appeared as early as 15 minutes after initiation of the infusion. It was mostly manifested as a flushed, erythematous rash on the face, neck, and around the ears. Less frequently, the rash was distributed all over the body. Pruritus was usually localized to the upper trunk but was also generalized (2 of 11 children).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216624 TI - Serial Munchausen syndrome by proxy. AB - Five cases of Munchausen syndrome by proxy (MSBP) are presented in which more than one child in the family was victimized. There was a high incidence of maternal psychiatric histories, marital difficulties, and Munchhausen syndrome in the mothers themselves. Seventy-one percent of the children in the families were known to be victims of MSBP; four of these children (31%) died. Multiple-child MSBP may reflect more significant maternal psychopathology than found in other cases of MSBP, or it may indicate the deteriorating consequences to the mother and other children in the family if this syndrome is not identified with the first child and effective interventions made. PMID- 2216625 TI - Outcome and predictors of outcome in pediatric submersion victims receiving prehospital care in King County, Washington. AB - Predictors of outcome in pediatric submersion victims treated by Seattle and King County's prehospital emergency services were studied. Victims less than 20 years old were identified from hospital admissions and paramedic and medical examiners' reports. The proportion of fatal or severe outcomes in patients were compared with various risk factors. Of 135 patients, 45 died and 5 had severe neurologic impairment. A subset of 38 victims found in cardiopulmonary arrest had a 32% survival rate, with 67% of survivors unimpaired or only mildly impaired. The two risk factors that occurred most commonly in victims who died or were severely impaired were submersion duration greater than 9 minutes (28 patients) and cardiopulmonary resuscitation duration longer than 25 minutes (20 patients). Both factors were ascertained in the prehospital phase of care. Submersion duration was associated with a steadily increasing risk of severe or fatal outcomes: 10% risk (7/67) for 0 to 5 minutes, 56% risk (5/9) for 6 to 9 minutes, 88% risk (21/25) for 10 to 25 minutes, 100% risk (4/4) for greater than 25 minutes. None of 20 children receiving greater than 25 minutes of cardiopulmonary resuscitation escaped death or severe neurologic impairment. Our rates for saving all victims, particularly victims in cardiopulmonary arrest, are considerably higher than has been reported before the children. Prompt prehospital advanced cardiac life support is the most effective means of medical intervention for the pediatric submersion victim. Prehospital information provided the most valuable predictors of outcome. PMID- 2216626 TI - Successful renal transplantation accelerates development in young uremic children. AB - To examine the impact of renal transplantation on subsequent development of children with chronic renal failure, 37 children undergoing primary renal transplantation at or before 30 months of age whose allograft functioned for at least 1 year were prospectively studied. Psychometric tests were performed an average of 4 months before transplantation; reevaluation was done an average of 14 months after surgery. Comparison of individual pretransplantation and posttransplantation mental development scores in 33 patients, assessed by either Bayley Mental Development Index or Stanford-Binet Intelligence Quotient, revealed an average increase of 12.6 (P less than .001). After transplantation, there was a significant improvement in mental performance in 12 of 18 patients (P less than .02) from the range of mild delay (Mental Development Index or Stanford-Binet IQ score = 50 to 69) to the range of normal mental development (greater than or equal to 70). The Bayley Psychomotor Development Index scores were frequently lower than Mental Development Index scores and also increased an average of 14.4 (P less than .01) after transplantation in all 12 patients with paired data. Significant individual improvement in occipital-frontal circumference standard deviation score (P less than .001) was noted in 24 children after transplantation. It is concluded that successful renal transplantation in young children with chronic renal failure is often associated with significant improvements in cognitive and psychomotor function, as well as improved cephalic growth. PMID- 2216627 TI - Exposure to a chloride-deficient formula during infancy: outcome at ages 9 and 10 years. AB - A school-based survey of the 1978 to 1979 birth cohort of two metropolitan Washington, DC, counties was conducted to find children who had been exposed to the chloride-deficient formulas Neo-Mull-Soy and Cho-Free during infancy. Children who had ingested other soy formulas that had an adequate chloride content were also found and matched to the exposed children by sex, race, birth weight, the age of the child, the mixed feeding status of the child, and maternal education. One hundred seventy-one of the exposed children and 261 soy control children were given a battery of psychologic tests in their homes to determine whether there had been any effect on intellectual development as a result of exposure to the chloride-deficient formulas. There were no differences in scores between the groups on the Wechsler Intelligence Scale for Children-Revised, the Boston Naming Test, the Rey-Osterrieth Test, or the FAS Verbal Fluency Test. There was no correlation between duration of exclusive exposure to the chloride deficient formulas and the Wechsler Intelligence Scale for Children-Revised Full Scale IQ Score (Pearson product-moment r = -.0825, P = .28). These results cannot be extrapolated to exposed children with documented hypochloremic metabolic alkalosis. It is concluded that in children without documented evidence of hypochloremic metabolic alkalosis, exposure to the chloride-deficient formulas Neo-Mull-Soy or Cho-Free during infancy has not resulted in any long-term adverse effects on cognitive development. PMID- 2216628 TI - Febrile status epilepticus. AB - As part of a study of status epilepticus in children (Maytal J, Shinnar S, Moshe SL, Alvarez LA. Pediatrics. 1989; 83:323-331); 44 children with febrile convulsions lasting more than 30 minutes were followed for a mean of 28 months (range 4 to 72). Thirty children were followed prospectively. Children with prior afebrile seizures or evidence of acute central nervous system infection were excluded. Nine (20%) children had prior neurological deficits. The duration of the febrile seizure was 0.5 to 1 hour in 41 cases (85%), 1 to 2 hours in 5 (10%), and greater than 2 hours in 2 children (5%). No child died or developed new neurological deficits following the seizures. The risk of recurrent seizures was increased, but only in the group with prior neurological abnormality. Six (66%) of these children had subsequent febrile seizures compared with 12 (34%) of the normal children (P = .08). Three (33%) had recurrent febrile status epilepticus compared with only 1 (3%) normal child (P = .023). The 2 children in the prospective arm of the study with recurrent febrile status epilepticus were both neurologically abnormal (P = .035). All 3 of the children who subsequently had afebrile seizures (2 prospective) were neurologically abnormal (P = .006 overall, P = .035 for prospective only). It is concluded that the occurrence of febrile status epilepticus in a neurologically impaired child is a risk factor for subsequent febrile as well as afebrile seizures. The occurrence of febrile status epilepticus in an otherwise normal child does not significantly increase the risk for subsequent febrile (brief or prolonged) or afebrile seizures in the first few years following the episode. PMID- 2216630 TI - Real-time ultrasound and color-Doppler imaging in pulmonary sequestration. PMID- 2216629 TI - Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine in vaccinated children who developed Haemophilus disease. PMID- 2216631 TI - Just say no! Drugs and febrile seizures. PMID- 2216632 TI - Prehospital care for victims of submersion. PMID- 2216634 TI - American Academy of Pediatrics Committee on Children with Disabilities and Committee on School Health: Children with health impairments in schools. PMID- 2216633 TI - Improving access to health care for children, youth, and pregnant women. PMID- 2216635 TI - American Academy of Pediatrics Committee on Substance Abuse: Drug-exposed infants. PMID- 2216636 TI - American Academy of Pediatrics Committee on Nutrition: Practical significance of lactose intolerance in children: supplement. PMID- 2216637 TI - Sex-specific dysanapsis and the effect of passive smoking among asthmatics. PMID- 2216638 TI - Clofibrate treatment of neonatal jaundice. PMID- 2216639 TI - Neonatal choreoathetosis following prenatal exposure to oral contraceptives. PMID- 2216640 TI - Bacterial flora of "normal" sinuses. PMID- 2216641 TI - Retinal hemorrhage after cardiopulmonary resuscitation. PMID- 2216642 TI - Aluminum and infants. PMID- 2216643 TI - American Academy of Pediatrics Report of the Subcommittee on Assessment and Methodologic Issues in the Management of Pain in Childhood Cancer. PMID- 2216644 TI - American Academy of Pediatrics Report of the Subcommittee on Disease-Related Pain in Childhood Cancer. PMID- 2216645 TI - American Academy of Pediatrics Report of the Subcommittee on the Management of Pain Associated with Procedures in Children with Cancer. PMID- 2216646 TI - Research priorities as defined by the subcommittees. PMID- 2216647 TI - Redundancy phenomena are affected by response requirements. AB - Results are reported for two go/no-go reaction time (RT) experiments, in which the redundant targets advantage was investigated. These experiments were replications of two earlier choice reaction time (CRT) experiments, in which letter stimuli were used. Important differences between the go/no-go RT experiments and the CRT experiments were obtained. Equal and significant redundancy advantages were obtained whether redundant targets were compared with a single target presented with a noise letter or without noise. In the CRT experiments, the advantage was not obtained in the comparison with a single target presented alone. Noise letters did not slow the RTs to single targets with which they were presented as was the case with CRT. Since the differing results of the two procedures depend on the response requirements, explanation of differing CRT data in terms of perceptual or attentional concepts is probably inappropriate. The presence and absence of response competition in the two situations may be the best interpretation. The results tend to support a conclusion of the parallel processing of two letter stimuli separated spatially by as much as 3 degrees. PMID- 2216648 TI - Auditory psychomotor coordination and visual search performance. AB - In Experiments 1 and 2, the time to locate and identify a visual target (visual search performance in a two-alternative forced-choice paradigm) was measured as a function of the location of the target relative to the subject's initial line of gaze. In Experiment 1, tests were conducted within a 260 degree region on the horizontal plane at a fixed elevation (eye level). In Experiment 2, the position of the target was varied in both the horizontal (260 degrees) and the vertical (+/- 46 degrees from the initial line of gaze) planes. In both experiments, and for all locations tested, the time required to conduct a visual search was reduced substantially (175-1,200 msec) when a 10-Hz click train was presented from the same location as that occupied by the visual target. Significant differences in latencies were still evident when the visual target was located within 10 degrees of the initial line of gaze (central visual field). In Experiment 3, we examined head and eye movements that occur as subjects attempt to locate a sound source. Concurrent movements of the head and eyes are commonly encountered during auditorily directed search behavior. In over half of the trials, eyelid closures were apparent as the subjects attempted to orient themselves toward the sound source. The results from these experiments support the hypothesis that the auditory spatial channel has a significant role in regulating visual gaze. PMID- 2216649 TI - Cross-gender perceptions of facial attributes and their relation to attractiveness: do we see them differently than they see us? AB - Examination of perceptions of human facial attributes revealed that individual attributes are similarly perceived by males and females. However, patterns of attribute interrelationships differ as a function of gender of the face. Undergraduate students (N = 280) rated pictures of 40 male or female Caucasians on 12 physical attributes (e.g., nose size, face width) and overall attractiveness. The four sets of attribute ratings (defined by rater gender and picture gender) were submitted to principal components analyses, and five-factor solutions were found for each condition (accounting for about 76% of the variance). Comparisons of the four component solutions using confirmatory factor procedures revealed that male and female raters share one factor structure when rating photographs of female faces and another factor structure when rating photographs of male faces. Multiple regression analyses revealed that the patterns of attribute interrelationships were not "perceptual units" in the perception of attractiveness, and that different "rules" are used to assess the attractiveness of male and female stimuli faces. The importance of these results for models of facial attractiveness and interfacial similarity judgements are discussed. PMID- 2216650 TI - Lack of evidence for a tactual Poggendorff illusion. AB - Lucca, Dellantonio, and Riggio (1986) reported large distortions in a tactual analogue of the visual Poggendorff illusion. They also reported large effects in the direction opposite to the visual illusion, which they termed "inversions." However, their evidence for such effects is questionable; they used what we consider to be inappropriate measurement and analysis procedures. In attempting to replicate their experiment, and in conducting four additional experiments, we found no evidence at all for their alleged tactual analogue of the visual Poggendorff effect. Instead, we demonstrated that "inversions" are likely due to the use of a raised stimulus display that causes artifactual mistracking, which is totally unrelated to normal mechanisms of alignment judgment. We also discuss the possible role of intersensory factors in the generation of tactual illusions. PMID- 2216651 TI - Voluntary allocation versus automatic capture of visual attention. AB - Is there a difference in the kind of attention elicited by an abrupt-onset peripheral cue and that elicited by an instruction (e.g., a central arrow cue) to move attention to a peripheral location? In Experiment 1, we found that peripheral cues are no more effective in orienting attention than are central cues. No evidence was found for separable attentional systems consisting of a volitional response to central cues and an automatic response triggered only by peripheral cues. Rather, an identical or similar attentional process seems to be activated by either type of cue, although perhaps in different ways. Peripheral cues seem to have an automatic component, however, in that once attention is engaged by a peripheral cue, it cannot easily be disengaged for refocus elsewhere. In Experiment 2, after several sessions of practice, subjects were able to circumvent automatic attentional capture by an abrupt-onset peripheral cue and to volitionally redirect the focus of attention. Thus, attentional capture by abrupt-onset stimuli is not strongly automatic. PMID- 2216652 TI - Mental retardation and perception of global motion. AB - We have found that mildly mentally retarded adults are impaired in their perception of global stereoscopic forms (Fox & Oross, 1988) in ways that cannot be attributed to peripheral visual deficits or failures to comprehend. To assess the generality of that result, we measured the ability of mentally retarded adults to perceive kinematographic forms. Mentally retarded and nonretarded adults were presented with a two-choice, forced-choice detection task requiring the location of a target's spatial position. The discriminability of the forms was varied by systematic reductions in both element density and temporal correlation. We found that, relative to nonretarded adults, mentally retarded adults exhibited large qualitative deficits in their ability to discriminate these kinematographic forms when either density or correlation was reduced. After considering a number of alternative interpretations of these data based on factors such as peripheral visual impairment and a failure to attend, we could find none more compelling than a perceptual interpretation, which posits a deficit within the short-range motion system. PMID- 2216654 TI - Visual-touch perceptual equivalence for shape information in children and adults. AB - Although there has been substantial developmental research which has compared shape information processing performance under visual and touch conditions, there has been little work that bears on the shape attributes that are routinely employed, or on the similarity between shape attributes employed by adults and those employed by children. The present research was carried out to investigate the visual-touch perceptual equivalence of young children, using multidimensional scaling techniques, and to compare the visual and touch perceptual structures of this age group with those of adults. The results provide evidence for adult-like perceptions of shape among 6-year-olds, in terms of both the patterns of interstimulus similarities and the shape attributes attended to by children using each modality. In addition, it was found that children have somewhat more visual touch perceptual equivalence than adults do. PMID- 2216653 TI - The role of discontinuities in the perception of subjective figures. AB - Recently we proposed a theory of visual interpolation (Kellman & Shipley, in press) that addresses a variety of unit formation phenomena, including the perception of partly occluded objects and subjective figures. A basic notion of the theory is that discontinuities in the first derivative of projected edges are the initiating conditions for interpolation of boundaries that are not physically specified. In this paper, we report four experiments in which this claim was tested in the domain of subjective figures. Experiments 1 and 2 demonstrate that discontinuities in the first derivative of the edges of inducing elements have a clear effect on the frequency of report and the perceived clarity of simple subjective figures. Similar effects are found when unfamiliar subjective figures and inducing elements are used (Experiment 3). Experiment 4 rules out the possibility that the discontinuities in the first derivative merely add to the clarity of subjective figures. These experiments suggest that first-order discontinuities play a central role in unit formation. PMID- 2216655 TI - The effects of position cues on the appearance of stimulus elements in a bistable apparent movement display. AB - A modified version of the Ternus display was used to assess the relative effects of element position cues on reports of group and end-to-end movement. In this display, two rows of stimulus elements are joined by connecting lines. In one version of the display, the connecting lines remain stationary across frames, facilitating the interpretation that the associated stimulus elements also remain stationary. In another version of the display, one end of the connecting lines shifts horizontally from frame to fame, facilitating the interpretation that the associated stimulus elements have also shifted. The experiment showed that when the connecting lines remain stationary, reports of end-to-end movement increase, regardless of the interstimulus interval (ISI) at which the frames alternate. When the connecting lines shift, reports of group movement increase, regardless of ISI. Theoretical interpretations of the results involving both relatively low level motion signals and higher order perceptual influences are considered. PMID- 2216656 TI - Alcohol impairs visual presence/absence detection more for females than for males. AB - Ninety subjects (45 males, 45 females) were given 0.0, 0.5, or 1.0 ml/kg body weight of 190-proof ethanol and tested for chance-level presence/absence detection thresholds with energy-masked presentations of traffic signs and blank inputs. Alcohol produced higher blood alcohol concentration (BAC) levels, and higher detection threshold durations, for females than for males. These results indicate that alcohol influences precortical visual processing and that the influence is greater for females than for males. The higher bioavailability of alcohol in women is likely due to less gastric oxidation of ethanol in women than in men. PMID- 2216657 TI - Methodological implications of interaural correlation: count heads not ears. AB - In a sample of 425 subjects, pure-tone hearing thresholds between the right and left ears were shown to have an average correlation of .885 (or .783 with age partialed out). This high interaural correlation is shown to invalidate the experimental procedure of entering data on the basis of "ears," where each subject can contribute one or two audiograms to the data pool, since such aggregation is demonstrated to produce spuriously high levels of apparent statistical significance in inferential statistical tests. PMID- 2216659 TI - Biomedical innovation and world health. PMID- 2216658 TI - Do we know the cause(s) of AIDS? PMID- 2216660 TI - A rationale for centuries of therapeutic bloodletting: antipyretic therapy for febrile diseases. PMID- 2216661 TI - The dynamics of free cholesterol exchange may be critical for endothelial cell membranes in the brain. PMID- 2216662 TI - Leisure for creative thought: planned respites from classroom and laboratory. PMID- 2216663 TI - Thoracic outlet syndrome and dysfunction of the temporomandibular joint: proved pathology or pseudosyndromes? PMID- 2216664 TI - Health and fitness. PMID- 2216665 TI - Vampires, porphyria, and the media: medicalization of a myth. PMID- 2216666 TI - The abused woman and her family of origin. AB - The abuse of women in significant heterosexual relationships is an important societal problem in the United States. Structural family therapy offers a useful perspective to nurse therapists working with abused women who have left the abusive relationship to rejoin their families of origin. Common errors are avoided if the abused woman and her family are diagnosed within the system's context of structural family therapy. Dysfunctional transactional patterns that originated in the abused woman's childhood or adolescent years can be challenged at their source. PMID- 2216667 TI - Counseling rape victims: the nursing challenge. AB - Rape and sexual assaults are a pervasive problem encountered by women in our society today. Treatment approaches specifically useful with rape victims have been identified by nursing staff at the Sexual Assault Resource Service (SARS). This nursing research demonstration treatment program funded by the National Institute of Mental Health identifies seven essential components of counseling during the initial crisis period, which are discussed in this article. PMID- 2216669 TI - A new level of inhumanity to helpless children. PMID- 2216668 TI - Hope and spiritual well-being: essentials for living with AIDS. AB - Without a cure on the horizon there is a need to identify ways to sustain hope and spiritual well-being in patients with AIDS. This article examines the impact of AIDS on the emotional and spiritual health of its victims and summarizes current research findings on spiritual well-being in the ill. It also summarizes the authors' study on hope and existential and spiritual well-being in a group of 65 adult male patients who were either serum positive for the human immunodeficient virus or who had been diagnosed with AIDS Related Complex or AIDS. PMID- 2216670 TI - Interpersonal "dances": reflections of Harriet Goldhor Lerner, PhD. Interview by Deb Kirmer. PMID- 2216671 TI - Abstracts of posters. Drug utilization research and pharmacoepidemiology meeting. Utrecht (The Netherlands), 27 September 1990. PMID- 2216672 TI - Abstracts of papers. Optimizing clinical pharmacy practice. 19th European Symposium on Clinical Pharmacy. Barcelona (Spain), 24-26 October 1990. PMID- 2216673 TI - Abstracts of papers. Pharmacological meeting. Utrecht (The Netherlands), 7 November-12 December 1990. PMID- 2216674 TI - Abstracts of papers. Biopharmaceutical meeting. Leiden (The Netherlands), 30 November 1990. PMID- 2216675 TI - [How many teeth does a person need?]. PMID- 2216676 TI - [Bone transplantation in combination with implants]. PMID- 2216677 TI - [Telescopic prostheses]. PMID- 2216678 TI - Interview with Hildegard E. Peplau. Interview by Shirley Smoyak. PMID- 2216680 TI - Implications of the Cruzan decisions for nurses. PMID- 2216679 TI - First, do no harm: healthcare workers with AIDS. PMID- 2216682 TI - Innovations in nursing education administration. PMID- 2216681 TI - Intercultural encounter: Filipino value system in the American workplace. PMID- 2216684 TI - [Regulation of the blood circulation: the significance of the renin-angiotension system]. PMID- 2216683 TI - [Private and public health care--new patterns]. PMID- 2216685 TI - [Treatment of hypertension using angiotensin-converting enzyme inhibitors]. AB - Angiotensin conversion enzyme inhibitors (ACE inhibitors) comprise a relatively new group of potent antihypertensives. They are today among the most used preparations for reducing blood pressure. ACE inhibitors may be used for treatment of almost all forms and degrees of hypertension. By reason of the reduction of the resistance in the peripheral vessels the blood pressure drops by 12-20 per cent, both at rest and during muscular effort, without diminution of the heart's pump function. The autonomic reflexes are unchanged and the circulation in the kidneys and the brain is retained. ACE inhibition does not result in fluid retention. In adequate doses the drugs are tolerated and give few side-effects provided that the patient is not dehydrated. PMID- 2216686 TI - [ACE inhibitors in the treatment of heart failure]. AB - Cardiac insufficiency is a clinical syndrome which presents several distinctive findings but is nevertheless difficult to define both clinically and in the scientific literature. In this article we maintain that cardiac insufficiency is a clinical condition characterized by symptomatic fluid retention on a cardiac basis, combined with signs of impaired pumping in the form of reduced capacity and/or other organic effects such as reduced renal function. The renin angiotensin system is of cardinal importance once cardiac insufficiency is established and ACE inhibition is of essential significance for the treatment. It is not yet clear whether it is possible to prevent the onset of cardiac insufficiency in patients at high risk thereof. Current studies may answer this question. PMID- 2216687 TI - [ACE inhibitors' effect on kidney function]. AB - ACE-inhibitors have many positive features, when treating patients with progressive renal failure. These patients have high mortality in cardiac and vascular complications. It is therefore important to treat hypertension in these patients with drugs which do not have negative effects on lipid-, glucose, or electrolyte-metabolism, and ACE inhibition fulfills these requirements. These drugs decrease left ventricular hypertrophy, which is a positive prognostic sign of hypertensive patients, too. Contrary to regular diuretics, ACE-inhibition does not cause the negative effects associated with activation of the renin angiotensin system. In many patients ACE-inhibitors decrease proteinuria to a higher degree than other antihypertensive drugs, and this may be an important clinical advantage, particularly in nephrotic patients. ACE inhibition might slow progressive renal failure. This effect may be associated with advantageous intraglomerular hemodynamic changes, but may also associate with inhibition of negative effects of angiotensin II on mesangial hypertrophy and matrix proliferation. PMID- 2216688 TI - [Skin pigmentation, nevi and sunshine as etiological factors in cutaneous malignant melanoma]. AB - In this review, an attempt is made to provide a status on the current knowledge concerning the connection between skin pigmentation, naevi, sunshine and development of cutaneous malignant melanoma. Our knowledge is based partly on descriptive epidemiological reports, and partly on information obtained from case control investigations. The descriptive investigations have revealed characteristic geographical and ethnic differences in the distribution of the disease. Cancer registry data have revealed a rapid increase in the incidence among white populations during the past 30-40 years with particularly pronounced increase for the areas of the body normally covered with clothes. Lacking consistency between indicators for cumulative exposure to sunlight and descriptive epidemiological studies have led to the hypothesis that intermittent exposure to sunlight is particularly harmful. Case control investigations have provided further support to this hypothesis and have demonstrated that sunbathing is associated with an increased risk for development of melanoma, particularly during childhood and particularly if it leads to sunburn. In addition, the risk of development of melanoma is increased in persons with a tendency to freckle and/or with many naevi. On this background, certain risk groups may be informed about prophylactic measures with subsequent possibility of reducing the number of new cases of cutaneous melanoma in the future. Finally, it is emphasized that the disease is multifactorial in origin and that the pathogenesis is not fully elucidated. PMID- 2216689 TI - [Development and new private health care options--complement and challenge for Swedish public health care]. PMID- 2216690 TI - [The private health care sector in Finland]. PMID- 2216691 TI - [Strategic possibilities for private hospitals in the 90s in Denmark]. PMID- 2216692 TI - [Scandinavian physicians' labor market balanced up till the turn of the century]. PMID- 2216693 TI - What's new on the AIDS front? PMID- 2216694 TI - NM public health nursing changing with the times. PMID- 2216695 TI - Leading the way in international volunteerism. PMID- 2216696 TI - Knowledge and use of smokeless tobacco by visitors to a state fair oral health exhibit. PMID- 2216697 TI - Carpal tunnel syndrome among Minnesota dental hygienists. PMID- 2216698 TI - Profile of Dr. Richard Rossi. PMID- 2216699 TI - A recruitment strategy for dental hygienists and dental assistants in northern Minnesota and Wisconsin. PMID- 2216700 TI - Expression of the interleukin 6 gene in acute myeloid leukemia and myelodysplastic syndromes: a report on 49 cases. AB - We studied the expression of IL 6 gene in 49 patients, including 21 chronic myelomonocytic leukemias (CML), 9 other myelodysplastic syndromes (MDS), 18 acute myeloid leukemias (11 M2 or M3 and 7 M4 or M5) and 1 case of acute biphenotypic lymphoid monocytic leukemia. IL 6 was found expressed only in the latter patient and in one patient with M5 acute myeloid leukemia. DNA analysis by Southern blot revealed no rearrangement in these 2 patients and in 10 of the other patients who showed no IL 6 expression. These results do not support an autocrine role for IL 6 in CMML or in other MDS. In acute myeloid leukemias, if expressed by leukemic cells, IL 6 seems to be restricted to cases with a monocytic component, although the number of patients was too small to draw any definite conclusion. PMID- 2216701 TI - Is translocation (8;21) a "favorable" cytogenetic rearrangement in acute myeloid leukemia? AB - Twenty-three patients with de novo acute myeloid leukemia (AML) and t(8;21) (q22;q22), including 2 children aged 7 and 14 and 21 adults aged 16 to 68 (median 29), were treated with intensive chemotherapy and 22 (96%) achieved complete remission (CR). Three were allografted in first CR. Median actuarial disease-free interval (DFI) was 17 months in the 22 patients and 14 months when the 3 allografted patients (who did not relapse) were excluded, as compared to 19.5 months in our whole series of AML treated according to the same protocol. After relapse, most patients with t(8;21) reached a second CR, but it was short, except in the 4 patients who were then allografted, and for whom follow-up is insufficient to draw any conclusion. Our findings suggest that, although it is associated with a high CR rate, AML with t(8;21) has a high incidence of relapses, especially in the first year of CR. The term "favorable" cytogenetic rearrangement may be misleading in such cases, and we believe that these patients should receive intensive post-consolidation therapy, possibly including an allograft whenever feasible. PMID- 2216702 TI - High-dose etoposide and cisplatin in refractory or recurrent non-Hodgkin's lymphomas (NHL). AB - Thirty-one patients, 13 adults and 18 children, were included in a phase II study of combined treatment with CDDP 40 mg/m2 and VP16 100 or 200 mg/m2 for 5 days. Fourteen patients were primary refractory to front-line treatment and 17 were treated at relapse (9 on therapy, 8 off therapy). Four were low-grade follicular lymphomas, 7 intermediate grade lymphomas, and 20 high grade lymphomas. One of the 14 primary refractory cases responded (CR) whereas 3 PR and 10 CR were observed among the 17 relapses. Toxicity was acceptable. 9 patients are still alive after bone marrow transplantation (median survival, 16 months). This combination is an effective salvage regime before autologous bone marrow transplantation for relapsed NHL, but cannot be recommended for progression on front-line therapy. PMID- 2216703 TI - Evaluation of residual masses after lymphoma treatment: the contribution of gallium 67 tomoscintigraphy. AB - 19 tomoscintigraphies using gallium 67 were performed in 15 patients with Hodgkin's or non-Hodgkin's lymphoma who had a residual mass after treatment. The isotope was never fixed in fibrous masses but was always concentrated in actively growing masses. In five cases histology confirmed these findings. It is recommended that scintigraphy should be considered in every case with a residual mass after treatment, where a decision regarding further treatment is required. PMID- 2216704 TI - Comparative immunochemical analysis of membrane proteins from human platelets and endothelial cells. AB - We have studied the expression of immunochemically-related membrane proteins on human platelets and human umbilical vein endothelial cells (EC) by using cross immunoprecipitation of 125I, surface-labeled cell extracts by cell-specific antisera, coupled to one- or two-dimensional SDS-PAGE. From 125I-labeled EC, an anti-platelet antiserum was found to immunoprecipitate major surface polypeptides comigrating with platelet GPIa, GPIIa and GPIIIa, and a protein with relative molecular mass Mr = 54,000. On the other hand, anti-EC antisera precipitated mostly GPIa, GPIc, GPIIa and GPIIIa from 125I-labeled platelets. These results supported previous reports demonstrating shared major membrane glycoproteins on platelets and EC, and suggested that the similar antigenicities in platelets and endothelial cells could play an important role in the pathogenesis of thrombosis and hemostasis in some immunologic disorders. PMID- 2216705 TI - Use of Coulter VCS for differential leukocyte counts. AB - The Coulter VCS is a tridimensional flow cytometer designed for differential leukocyte counting on the basis of cell volume, light scatter and conductivity. The VCS differential performed on 192 non-flagged samples was compared with the blood smear, taken as the reference method. A good correspondence was found between the two methods. Two hundred and seventy pathological samples were studied by both the VCS and the reference method: 219 samples with no anomalies other than quantitative changes and 51 with abnormal cells. 41% of the quantitative changes presented without any flag; 59% were flagged: either isolated X5 flags (30%) or other flags needing blood smear review (29%). Samples with abnormal cells (51) were detected with one or more flags: X3 + X6 in myelocytic disease X2 + X7 in lymphocytic disease. Only two (1 hairy cell leukemia, 1 lymphoma) were not flagged; however in these cases the abnormalities were revealed by the presence of either a striking neutropenia or a lymphocytosis. This corresponded to a false-negative rate of 0.4% in the group studied. Further studies were performed on patients with X5 flagging only. The VCS differential was compared to the optical differential as a reference method. There was a good relationship between the two methods; thus X5 flagging could be established without further slide review provided the numerical values were within the range valid for the laboratory. Thus, in our system of working, both VCS flags (except isolated X5) and laboratory performance limits were taken into account as regards the need for blood smear review. This resulted in a review rate of 15%. PMID- 2216706 TI - IPTG-dependent vaccinia virus: identification of a virus protein enabling virion envelopment by Golgi membrane and egress. AB - A novel method has been developed to study the functional roles of individual vaccinia virus gene products that is neither limited by the possible essentiality of the target gene nor by the availability of conditional lethal mutants. The system utilises the E. coli lac repressor protein, the operator sequence to which it binds and the specific inducer IPTG. It allows the generation of recombinant viruses in which the expression of any chosen gene, and hence virus replication, can be externally controlled. In principle, this system is broadly applicable to the functional analysis of genes in any large DNA virus. This approach has demonstrated that the gene encoding the 14 kDa membrane protein of vaccinia virus is non-essential for the production of infectious intracellular virus particles, but essential for the envelopment of intracellular virions by Golgi membrane and for egress of mature extracellular viral particles. This is the first vaccinia virus protein shown to be specifically required for these processes. In vivo this system may prove useful as a means of attenuating recombinant vaccinia virus vaccines by preventing virus spread without reducing the amount of the foreign antigen expressed in each infected cell. Attenuation of other live virus vaccines may be developed in a similar way. PMID- 2216707 TI - The mouse rpL7a gene is typical of other ribosomal protein genes in it's 5' region but differs in being located in a tight cluster of CpG-rich islands. AB - The two major transcriptional start sites of the mouse ribosomal protein L7a gene (rpL7a) (formerly Surf-3) have been mapped to two cytidine residues separated by 4 bp embedded in a polypyrimidine tract of 21 bp. The rpL7a gene contains a small first exon (25-29 bp) and a small 5' untranslated leader sequence (22-26 bp). Its transcriptional start sites are not preceded by a canonical TATA box motif and its 5' end is located in a CpG-rich island. These are all features found associated with the five other functional mammalian ribosomal protein genes which have been previously characterized. The mouse rpL7a gene is found within a very tight cluster of six genes associated with 4 CpG-rich islands located in 32 kb of genomic DNA. Unique DNA probes located both upstream and downstream of the mouse rpL30 and rpL32 genes used on Southern blots of mouse DNA cleaved with a variety of CpG-rich island specific restriction enzymes did not detect CpG-rich islands in the close vicinity of these ribosomal protein genes. Thus the clustering of CpG-rich islands associated with rpL7a does not appear to be a general feature of mammalian ribosomal protein genes. PMID- 2216708 TI - Uridine branch acceptor is a cis-acting element involved in regulation of the alternative processing of calcitonin/CGRP-l pre-mRNA. AB - The human calcitonin/CGRP-I (CALC-I) gene contains 6 exons and encodes two polypeptide precursors. In thyroid C-cells, calcitonin (CT) mRNA is produced by splicing of exons 1-2-3 to exon 4 (CT-encoding) and polyadenylation at exon 4. CGRP-I mRNA is produced in particular neural cells by splicing of exons 1-2-3 to exon 5 (CGRP-I-encoding) and the polyadenylated exon 6. We previously reported that model precursor RNAs containing the exon 3 to exon 5 region of the CALC-I gene are processed predominantly into CGRP-I mRNA in vitro, in nuclear extracts of several cell types (neural and non-neural). Using truncated precursor RNAs containing only the exon 3 to exon 4 region of the CALC-I gene it was shown that CT splicing is an inefficient reaction in which a uridine residue serves as the major site of lariat formation. Here we report that the low CT splicing efficiency and the dominance of CGRP-I splicing over CT splicing in vitro are primarily due to the usage of the CT-specific uridine branch acceptor. Mutation of this uridine residue into an adenosine residue resulted in a strong increase in CT splicing efficiency causing a reversal of the splicing pattern. In addition, it was shown that this point mutation also increased CT splicing efficiency in vivo. These results and data obtained from other experiments involving mutation of the CT splice acceptor site suggest that the uridine branch acceptor is a cis-acting element involved in regulation of the alternative processing of the CALC-I pre-mRNA. PMID- 2216709 TI - Evidence for a feedback regulated back-up promoter which controls permanent expression of a Dictyostelium gene. AB - We have previously described the elements of two overlapping promoters regulating differential expression of the Dictyostelium P8A7 gene. One promoter was constitutively active but stimulated during development (S-promoter), while the other (L-promoter) was found to be induced by a variety of stimuli. This effect was mediated by the induction (i-) element. By a series of antisense transformation experiments we here provide evidence that this element is the target of a feedback control circuit. In wild type cells, feedback regulation activates the L-promoter in unfavourable environmental situations when transcription from the S-promoter is insufficient to generate adequate amounts of protein. A model for the function of the feedback loop under natural and experimental conditions is presented. PMID- 2216710 TI - A single mutation in 16S rRNA that affects mRNA binding and translation termination. AB - A single base change in 16S rRNA (C726 to G) has previously been shown to have a dramatic effect on protein synthesis in E. coli (1). This paper more specifically details the effects of the mutation on mRNA binding and translation-termination. The in vitro technique of toeprinting (2) was used to demonstrate that 30S subunits containing the mutation 726G had an altered binding affinity for mRNA by comparison to the wild type. In addition, expression of the mutant ribosomes in vivo resulted in exclusive suppression of the UGA nonsense codon. This effect was supported by in vitro studies that showed the mutant ribosomes to have an altered binding affinity for Release Factor-2. PMID- 2216711 TI - Long (dA)n.(dT)n tracts can form intramolecular triplexes under superhelical stress. AB - Plasmids containing long tracts of (dA)n.(dT)n have been prepared and their conformations examined in linear and supercoiled DNA using a series of chemical and enzymic probes which are known to be sensitive to unusual DNA structures. Under superhelical stress and in the presence of magnesium the sequence T69.A69 adopts a conformation at pH 8.0 consistent with the formation of an intramolecular DNA triplex. Site specific cleavage of the supercoiled plasmid by single-strand specific nucleases occurs within the A.T insert; the 5'-end of the purine strand is sensitive to reaction with diethylpyrocarbonate while the central 5-6 bases of the pyrimidine strand are reactive to osmium tetroxide. By contrast shorter inserts of A33.T33 and A23.T23 do not appear to form unusual structures. PMID- 2216712 TI - Removal of double-stranded contaminants from RNA transcripts: synthesis of adenovirus VA RNAI from a T7 vector. AB - Bacteriophage RNA polymerases are widely used to synthesize defined RNAs on a large scale in vitro. Unfortunately, the RNA product contains a small proportion of contaminating RNAs, including complementary species, which can lead to errors of interpretation. We cloned the gene encoding Ad2 VA RNAI into a vector containing a T7 RNA polymerase promoter in order to generate large quantities of VA RNA for the study of its interaction with the dsRNA-dependent protein kinase DAI. Exact copies of VA RNAI were synthesized efficiently, but were contaminated with small amounts of dsRNA which activated DAI and confounded interpretation of kinase assays. We therefore developed a method to remove the dsRNA contaminants, allowing VA RNAI and mutants to be tested for their ability to activate or inhibit DAI. This method appears to be generally applicable. PMID- 2216713 TI - Direct detection and automated sequencing of individual alleles after electrophoretic strand separation: identification of a common nonsense mutation in exon 9 of the human lipoprotein lipase gene. AB - Large-scale screening by direct sequencing of DNA to detect molecular variants remains a laborious endeavor whose difficulty is compounded by heterozygosity. We show that mobility shifts of single-stranded DNA electrophoresed under nondenaturing conditions can be used not only to detect variants (Orita,M. et al., 1989, Genomics, 5, 874-879), but also to separate and sequence directly individual alleles. In this manner, we have identified a common variant of human lipoprotein lipase resulting from a nonsense mutation in exon 9 of the gene. Whether this variant is of functional significance remains to be determined. PMID- 2216714 TI - Identification of a putative RNA helicase in E.coli. AB - The human p68 protein, an SV40 large T related antigen, is an RNA dependent ATPase and RNA helicase. It belongs to a new large and highly conserved gene family, the DEAD box proteins, whose members are involved in a variety of processes requiring manipulation of RNA secondary structure such as translation and splicing. Multiple DEAD box genes are present in S.cerevisiae, but only one has previously been described in E.coli. Low stringency screening of an E.coli genomic library with a p68 cDNA probe led to the identification of dbpA, a new E.coli DEAD box gene located at 29.6 minutes on the W3110 chromosome. We report here the nucleotide and deduced amino acid sequences of the gene. We have overexpressed dbpA from its own promoter on a high copy number plasmid and identified the gene product as a approximately 50 kD protein by immunoblotting with an anti-DEAD antibody. PMID- 2216715 TI - Site specific functionalization of oligonucleotides for attaching two different reporter groups. AB - The synthesis of an oligonucleotide functionalized to attach two different reporter groups at specific internucleotide linkages is described. To incorporate the amine specific reporter group the internucleotide linkage is modified to phosphoramidate (N-1-aminoalkyl) and for a thiol specific reporter group the internucleotide linkage is modified to a phosphorothioate diester. The synthetic cycle for introducing the modified internucleotide linkages at specific sites can be carried out using an automated DNA synthesizer. Combination of reporter groups have been attached successfully. PMID- 2216716 TI - Cloned origin of DNA replication in c-myc gene can function and be transmitted in transgenic mice in an episomal state. AB - The c-myc protein has recently been shown to interact with a region possessing putative origin of DNA replication and enhancer activities located 2 kb upstream of the c-myc gene itself. Transgenic mice were obtained by injecting constructs containing this region, termed pmyc(H-P), into fertilized mouse eggs. The transgenic elements were capable of efficient replication in all mouse tissues examined and were maintained in an episomal state even in highly differentiated cells. Moreover, pmyc(H-P) was transmittable to the progeny throughout several generations, which suggests that the fragment derived from the region upstream of the c-myc gene possesses sequences necessary for partition, stability and DNA replication of the plasmid in the cells. In addition, we have shown that the plasmid might be captured only by eggs, not by sperm. PMID- 2216717 TI - Chemical synthesis of biologically active oligoribonucleotides using beta cyanoethyl protected ribonucleoside phosphoramidites. AB - The preparation of fully protected diisopropylamino-beta-cyanoethyl ribonucleoside phosphoramidites with regioisomeric purity greater than 99.95% is described. It is demonstrated that the combination of standard DNA protecting groups, 5'-O-DMT, N-Bz (Ade and Cyt), N-iBu (Gua), beta-cyanoethyl for phosphate, in conjunction with TBDMS for 2'-hydroxyl protection, constitutes a reliable method for the preparation of fully active RNA. Average stepwise coupling yields in excess of 99% were achieved with these synthons on standard DNA synthesizers. Two steps completely deprotect the oligoribonucleotide and workup is reduced to a fifteen minute procedure. Further, it is shown that the deprotected oligoribonucleotides are free from 5'-2' linkages. This methodology was applied to the chemical synthesis of a 24-mer microhelix, a 35-mer minihelix and two halves of a catalytic 'Hammerhead Ribozyme'. These oligoribonucleotides were directly compared in two distinct biochemical assays with enzymatically (T7 RNA polymerase) prepared oligoribonucleotides and shown to possess equal or better activity. PMID- 2216718 TI - Pulse-field electrophoresis indicates full-length Mycoplasma chromosomes range widely in size. AB - Full-size linear chromosomes were prepared from mycoplasmas by using gamma irradiation to introduce one (on average) double-strand break in their circular chromosomes. Chromosome sizes were estimated by pulsed-field gel electrophoresis (PFGE) from the mobilities of these full-length molecules relative to DNA size references. Sizes estimated for Ureaplasma urealyticum T960 and 16 Mycoplasma species ranged from 684 kbp (M. hominis) to 1315 kbp (M. iowae). Using this sample, we found no correlation between the mobility of the full-size linear chromosomes and their G + C content. Sizes for A. laidlawii and A. hippikon were within the range expected from renaturation kinetics. PFGE size estimates are in good agreement with sizes determined by other methods, including electron microscopy, an ordered clone library, and summation of restriction fragments. Our estimates also agree with those from renaturation kinetics for both the largest and some of the smallest chromosomes, but in the intermediate size range, renaturation kinetics consistently provides lower values than PFGE or electron microscopy. Our PFGE estimates show that mycoplasma chromosomes span a continual range of sizes, with several intermediate values falling between the previously recognized large and small chromosome size clusters. PMID- 2216719 TI - The molecular basis for alternative splicing of the CABP1 transcripts in Dictyostelium discoideum. AB - We have determined the nucleotide sequence of the CABP1 gene from Dictyostelium discoideum. Together with previous data on cDNA sequences, we establish that alternative splicing of transcripts derived from this gene is responsible for the production of the two CABP1 subunits. RNA blot analysis suggested that alternative splicing of the CABP1 transcripts occurs during growth and throughout development. In addition, we have compiled the intron sequences of Dictyostelium pre-mRNAs and observed that the GUAAGU hexanucleotide at the 5' splice site is highly conserved. The 5' splice site of CABP1 deviates from the consensus hexanucleotide in having a sequence of GUAAUA. To assess the role of the modified 5' splice on differential splicing, we have constructed an actin-CABP1 fusion gene and transformed it into Dictyostelium cells. Analysis by immunoprecipitation, with anti-CABP1 antibody and amplification of specific cDNAs by polymerase chain reaction show that the transcripts generated by the fusion gene are alternatively spliced. When the 5' splice site of the fusion gene is mutated to conform to the consensus sequence, the resulting transcripts are constitutively spliced. These observations suggest that changes in positions 5 and 6 of the donor splice site are involved in the alternative splicing of the CABP1 transcripts. PMID- 2216720 TI - Developmentally regulated and erythroid-specific expression of the human embryonic beta-globin gene in transgenic mice. AB - Transgenic mice have proven to be an effective expression system for studying developmental control of the human fetal and adult beta-globin genes. In the current work we are interested in developing the transgenic mouse system for the study of the human embryonic beta-globin gene, epsilon. An epsilon-globin gene construction (HSII,I epsilon) containing the human epsilon-globin gene with 0.2 kb of 3' flanking sequence and 13.7 kb of extended 5' flanking region including the erythroid-specific DNase I super-hypersensitive sites HSI and HSII was made. This construction was injected into fertilized mouse ova, and its expression was analyzed in peripheral blood, brain, and liver samples of 13.5 day transgenic fetuses. Fetuses carrying intact copies of the transgene expressed human epsilon globin mRNA in their peripheral blood. Levels of expression of human epsilon globin mRNA in these transgenic mice ranged from 2% to 26% per gene copy of the endogenous mouse embryonic epsilon y-globin mRNA level. Furthermore, the human epsilon-globin transgene was expressed specifically in peripheral blood but not in brain or in liver which is an adult erythroid tissue at this stage. Thus, the HSII,I, epsilon transgene was expressed in an erythroid-specific and embryonic stage-specific manner in the transgenic mice. A human epsilon-globin gene construction that did not contain the distal upstream flanking region which includes the HSI and HSII sites, was not expressed in the embryos of transgenic mice. These data indicate that the human epsilon-globin gene with 5' flanking region extending to include DNase I super-hypersensitive sites HSI and HSII is sufficient for the developmentally specific activation of the human epsilon globin gene in erythroid tissue of transgenic mice. PMID- 2216721 TI - Reactive site polymorphism in the murine protease inhibitor gene family is delineated using a modification of the PCR reaction (PCR + 1). AB - Murine protease inhibitor (alpha 1-PI) proteins are encoded by a multigene family which has undergone recent duplication. It has been suggested that the evolution of diversity within this gene family may be driven by unusual selection for novel function at the reactive site of the duplicated members (1,2,3). In an attempt to use polymerase chain reaction (PCR) to generate and sequence clones spanning the polymorphic reactive site region, a PCR artifact was identified and determined to result from heteroduplex formation during the co-amplification of the related sequences in this multigene system. This artifact results in sequences which are combinatorial mosaics of the template sequences. We present a simple and general method (PCR + 1) for overcoming this artifact and demonstrate its application in delineating five distinct alpha 1-PI reactive site sequences in C57BL/6 mice, thus providing sequence information to generate gene-specific probes. The significance of the reactive site diversity in this protease inhibitor gene family is discussed as well as the general applications and limitations of the PCR + 1 technique. PMID- 2216723 TI - Autonomous replication sequences in an extrachromosomal element of a pathogenic Entamoeba histolytica. AB - Entamoeba histolytica possesses a 24.5 kilobase plasmid-like molecule which encodes for the organism's ribosomal RNAs. Sequence analysis of this extrachromosomal element revealed the presence of AT rich sequences which show homology to the origin of replication of other lower eucaryotes. An 802 bp fragment containing these sequences was cloned into a yeast shuttle vector lacking the origin of replication and the construct tested for its ability to replicate autonomously in yeast. Mitotic stability tests as well as evidence for plasmid maintenance indicate that the transformed cells contained self replicating episomes and not stably integrated molecules. The nucleotide sequence of this ARS-containing fragment is presented. PMID- 2216722 TI - Astrocytes and glioblastoma cells express novel octamer-DNA binding proteins distinct from the ubiquitous Oct-1 and B cell type Oct-2 proteins. AB - The 'octamer' sequence, ATGCAAAT or its complement ATTTGCAT, is a key element for the transcriptional regulation of immunoglobulin genes in B-lymphocytes as well as a number of housekeeping genes in all cell types. In lymphocytes, the octamer binding protein Oct-2A and variants thereof are thought to contribute to the B cell specific gene expression, while the ubiquitous protein Oct-1 seems to control general octamer site-dependent transcription. Various other genes, for example interleukin-1 and MHC class II genes, contain an octamer sequence in the promoter and are expressed in cells of both the immune and nervous systems. This prompted us to analyze the octamer-binding proteins in the latter cells. Using the electrophoretic mobility shift assay, at least six novel octamer binding proteins were detected in nuclear extracts of cultured mouse astrocytes. These proteins are differentially expressed in human glioblastoma and neuroblastoma cell lines. The nervous system-derived (N-Oct) proteins bound to the octamer DNA sequence in a manner which is indistinguishable from the Oct-1 and Oct-2A proteins. The relationship of the N-Oct proteins to Oct-1 and Oct-2A was analyzed by proteolytic clipping bandshift assays and by their reactivity towards antisera raised against recombinant Oct-1 and Oct-2A proteins. On the basis of these assays, all N-Oct-factors were found to be distinct from the ubiquitous Oct-1 and the lymphoid-specific Oct-2A proteins. In melanoma cells that contain the N-Oct-3 factor, a transfected lymphocyte-specific promoter was neither activated nor was it repressed upon contransfection with an Oct-2A expression vector. We therefore speculate that N-Oct-3 and other N-Oct factors have a specific role in gene expression in cells of the nervous system. PMID- 2216724 TI - Crystal and solution structures of the oligonucleotide d(ATGCGCAT)2: a combined X ray and NMR study. AB - A combined crystal-structure determination and NMR analysis of the octanucleotide d(ATGCGCAT)2 is reported. The X-ray analysis shows that the structure is A-form duplex in crystal state. The NMR study shows that in solution this sequence is B type. The conformational results from each technique are presented in detail. The implications of these findings in terms of conformational flexibility and ligand binding are discussed. PMID- 2216725 TI - Ternary interactions of spermine with DNA: 4'-epiadriamycin and other DNA: anthracycline complexes. AB - The recently developed anthracycline 4'-epiadriamycin, an anti-cancer drug with improved activity, differs from adriamycin by inversion of the stereochemistry at the 4'-position. We have cocrystallized 4'-epiadriamycin with the DNA hexamer d(CGATCG) and solved the structure to 1.5 A resolution using x-ray crystallography. One drug molecule binds at each d(CG) step of the hexamer duplex. The anthracycline sugar binds in the minor groove. A feature of this complex which distinguishes it from the earlier DNA:adriamycin complex is a direct hydrogen bond from the 4'-hydroxyl group of the anthracycline sugar to the adenine N3 on the floor of the DNA minor groove. This hydrogen bond results directly from inversion of the stereochemistry at the 4'-position. Spermine molecules bind in the major groove of this complex. In anthracycline complexes with d(CGATCG) a spermine molecule binds to a continuous hydrophobic zone formed by the 5-methyl and C6 of a thymidine, C5 and C6 of a cytidine and the chromophore of the anthracycline. This report discusses three anthracycline complexes with d(CGATCG) in which the spermine molecules have different conformations yet form extensive van der Waals contacts with the same hydrophobic zone. Our results suggest that these hydrophobic interactions of spermine are DNA sequence specific and provide insight into the question of whether DNA:spermine complexes are delocalized and dynamic or site-specific and static. PMID- 2216726 TI - Nucleotide sequence of the metapyrocatechase II (catechol 2,3-oxygenase II) gene mpcII from Alcaligenes eutrophus JMP 222. PMID- 2216728 TI - Nucleotide sequence and deduced amino acid sequence of new Lepidoptera-specific crystal protein gene from Bacillus thuringiensis. PMID- 2216727 TI - Nucleotide sequence of the bean leafroll luteovirus coat protein gene. PMID- 2216729 TI - Nucleotide sequence and deduced amino acid sequence of a cryIA(c) gene variant from Bacillus thuringiensis. PMID- 2216730 TI - Nucleotide sequence of the tolC gene of Escherichia coli. PMID- 2216731 TI - Full length cDNA sequence encoding canine pancreatic colipase. PMID- 2216732 TI - Sequence of a human liver cytochrome P-450 cDNA clone. PMID- 2216733 TI - Nucleotide sequence of the 18S ribosomal RNA gene from the Atlantic sea scallop Placopecten magellanicus (Gmelin, 1791). PMID- 2216735 TI - cDNA sequence of the 3'-coding region of PVY genome (the Chinese isolate). PMID- 2216734 TI - The sequence of Japanese quail ovalbumin cDNA. PMID- 2216736 TI - Nucleotide sequence of the gene encoding Clostridium botulinum neurotoxin type D. PMID- 2216737 TI - Nucleotide sequence of the cellobiohydrolase gene from Trichoderma viride. PMID- 2216738 TI - Sequence of the murine haemopoietic stem cell inhibitor/macrophage inflammatory protein 1 alpha gene. PMID- 2216739 TI - A plasmodial specific mRNA (plasmin C) from Physarum polycephalum encodes a small hydrophobic cysteine-rich protein. PMID- 2216740 TI - Gene sequence of feline tumor necrosis factor alpha. PMID- 2216741 TI - Gene sequence of porcine tumor necrosis factor alpha. PMID- 2216742 TI - Consensus sequence for HMG1-like DNA binding domains. PMID- 2216743 TI - Nucleotide sequence of the glyceraldehyde-3-phosphate dehydrogenase gene from Cryphonectria parasitica. PMID- 2216744 TI - Nucleotide and deduced amino acid sequence of the bovine adenovirus type 7 proteinase. PMID- 2216745 TI - Nucleotide and deduced amino acid sequence of the bovine adenovirus type 3 proteinase. PMID- 2216746 TI - Nucleotide sequence of the cDNA of a bovine 70 kilodalton heat shock cognate protein. PMID- 2216747 TI - The nucleotide sequence of the luxD gene of Xenorhabdus luminescens Hm. PMID- 2216749 TI - A simplified and improved method for the efficient double-stranded sequencing of mini-prep plasmid DNA. PMID- 2216748 TI - A new extraction procedure of autonomous DNA from eucaryotic cells, where DNA could be bound to proteins. PMID- 2216750 TI - A simplified method for in vivo footprinting using DMS. PMID- 2216751 TI - Identification of a factor IX point mutation using SSCP analysis and direct sequencing. PMID- 2216752 TI - Study of the sequence tagged site (STS) in the beginning of human apo A4 gene region. PMID- 2216754 TI - Structural and thermodynamic studies on the adenine.guanine mismatch in B-DNA. AB - The structure of the synthetic dodecamer d(CGCAAATTGGCG) has been shown by single crystal X-ray diffraction methods to be that of a B-DNA helix containing two A(anti).G(syn) base pairs. The refinement, based on data to a resolution of 2.25 A shows that the mismatch base pairs are held together by two hydrogen bonds. The syn-conformation of the guanine base of the mismatch is stabilised by hydrogen bonding to a network of solvent molecules in both the major and minor grooves. A pH-dependent ultraviolet melting study indicates that the duplex is stabilised by protonation, suggesting that the bases of the A.G mispair are present in their most common tautomeric forms and that the N(1)-atom of adenine is protonated. The structure refinement shows that there is some disorder in the sugar-phosphate backbone. PMID- 2216755 TI - The involvement of base 1054 in 16S rRNA for UGA stop codon dependent translational termination. AB - The deletion of the highly conserved cytidine nucleotide at position 1054 in E. coli 16S rRNA has been characterized to confer an UGA stop codon specific suppression activity which suggested a functional participation of small subunit rRNA in translational termination. Based on this structure-function correlation we constructed the three point mutations at site 1054, changing the wild-type C residue to an A, G or U base. The mutations were expressed from a complete plasmid encoded rRNA operon (rrnB) using a conditional expression system with the lambda PL-promoter. All three altered 16S rRNA molecules were expressed and incorporated into 70S ribosomal particles. Structural analysis of the protein and 16S rRNA moieties of the mutant ribosomes showed no differences when compared to wild-type particles. The phenotypic analysis revealed that only the 1054G base change led to a significantly reduced generation time of transformed cells, which could be correlated with the inability of the mutant ribosomes to specifically stop at UGA stop codons in vivo. The response towards UAA and UAG termination codons was not altered. Furthermore, in vitro RF-2 termination factor binding experiments indicated that the association behaviour of mutant ribosomes was not changed, enforcing the view that the UGA stop codon suppression is a direct consequence of the rRNA mutation. Taken together, these results argue for a direct participation of that 16S rRNA motif in UGA dependent translational termination and furthermore, suggest that termination factor binding and stop codon recognition are two separate steps of the termination event. PMID- 2216756 TI - T7 endonuclease I resolves Holliday junctions formed in vitro by RecA protein. AB - T7 endonuclease I is known to bind and cleave four-way junctions in DNA. Since these junctions serve as analogues of Holliday junctions that arise during genetic recombination, we have investigated the action of T7 endonuclease I on recombination intermediates containing Holliday junctions. We find that addition of T7 endonuclease I to strand exchange reactions catalysed by RecA protein of Escherichia coli leads to the formation of duplex products that correspond to 'patch' and 'splice' type recombinants. Resolution of the recombination intermediates occurs by the introduction of nicks at the site of the Holliday junction. The recombinant molecules contain 5'-phosphate and 3'-hydroxyl termini which may be ligated to restore the integrity of the DNA. PMID- 2216757 TI - A homologous subfamily of satellite III DNA on human chromosomes 14 and 22. AB - We describe a new subfamily of human satellite III DNA that is represented on two different acrocentric chromosomes. This DNA is composed of a tandemly repeated array of diverged 5-base-pair monomer units of the sequence GGAAT or GGAGT. These monomers are organised into a 1.37-kilobase higher-order structure that is itself tandemly reiterated. Using a panel of somatic cell hybrids containing specific human chromosomes, this higher-order structure is demonstrated on chromosomes 14 and 22, but not on the remaining acrocentric chromosomes. In situ hybridisation studies have localised the sequence to the proximal p-arm region of these chromosomes. Analysis by pulsed-field gel electrophoresis (PFGE) reveals that 70 110 copies of the higher-order structure are tandemly organised on a chromosome into a major domain which appears to be flanked on both sides by non-tandemly repeated genomic DNA. In addition, some of the satellite III sequences are interspersed over a number of other PFGE fragments. This study provides fundamental knowledge on the structure and evolution of the acrocentric chromosomes, and should extend our understanding of the complex process of interchromosomal interaction which may be responsible for Robertsonian translocation and meiotic nondisjunction involving these chromosomes. PMID- 2216753 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2216758 TI - Complex requirements for RNA polymerase III transcription of the Xenopus U6 promoter. AB - The role of various sequences in determining the RNA polymerase III (pol III) specificity of the Xenopus U6 gene promoter has been investigated. A sequence closely resembling an RNA polymerase II (pol II) TATA box, which has previously been implicated in determining the pol III specificity of the U6 promoter, was analyzed in detail. The U6 TATA-like element, in a different promoter context, is shown to be capable of mediating RNA polymerase II transcription both in vitro and in oocyte microinjection experiments. Extensive mutagenesis of the TATA-like element in the context of the pol III and pol II promoters leads to the conclusion that the sequence requirements for function in the two contexts are dissimilar, suggesting that different factors may be involved in mediating pol II and pol III transcription. Further, as implied by the above results, it is shown that the polymerase III specificity of the U6 gene is not solely dependent upon the TATA-like element but rather reflects complex interaction between multiple components of the promoter. PMID- 2216759 TI - In vivo and in vitro analyses of an intron-encoded DNA endonuclease from yeast mitochondria. Recognition site by site-directed mutagenesis. AB - The pal 4 nuclease (termed I-Sce II) is encoded in the group I al 4 intron of the COX I gene of Saccharomyces cerevisiae. It introduces a specific double-strand break at the junction of the two exons A4-A5 and thus mediates the insertion of the intron into an intronless strain. To define the sequence recognized by pal 4 we introduced 35 single mutations in its target sequence and examined their cleavage properties either in vivo in E. coli (when different forms of the pal 4 proteins were artificially produced) or in vitro with mitochondrial extracts of a mutant yeast strain blocked in the splicing of the al 4 intron. We also detected the pal 4 DNA endonuclease activity in extracts of the wild type strain. The results suggest that 6 to 9 noncontiguous bases in the 17 base-pair region examined are necessary for pal 4 nuclease to bind and cleave its recognition site. We observed that the pal 4 nuclease specificity can be significantly different with the different forms of the protein thus explaining why only some forms are highly toxic in E. coli. This study shows that pal 4 recognition site is a complex phenomenon and this might have evolutionary implications on the transfer properties of the intron. PMID- 2216760 TI - Linearization of baculovirus DNA enhances the recovery of recombinant virus expression vectors. AB - Engineered derivatives of Autographa californica multiple nucleocapsid nuclear polyhedrosis virus (AcMNPV) possessing a unique restriction site provide a source of viral DNA that can be linearized by digestion with a specific endonuclease. Circular or linearized DNA from two such viruses were compared in terms of their infectivity and recombinogenic activities. The linear forms were 15- to 150-fold less infectious than the corresponding circular forms, when transfected into Spodoptera frugiperda cells using the calcium phosphate method. Linear viral DNA was, however, proficient at recombination on co-transfection with an appropriate transfer vector. Up to 30% of the progeny viruses were recombinant, a 10-fold higher fraction of recombinants than was obtained from co-transfections with circular AcMNPV DNA. The isolation of a recombinant baculovirus expression vector from any of the AcMNPV transfer vectors currently in use can thus be facilitated by linearization of the viral DNA at the appropriate location. PMID- 2216761 TI - Rat DNA polymerase beta gene can join in excision repair of Escherichia coli. AB - Though DNA polymerase I (poll) of Escherichia (E.) coli is understood to play a role in repair synthesis of excision repair, it is still obscure whether DNA polymerase beta (pol beta) plays a similar role in eukaryotic cells. To estimate the role of pol beta in excision repair processes, we inserted the rat pol beta gene into several mutant E. coli defective in a diverse set of enzymatic activities of poll. UV resistance was seen only when the 5'----3' exonuclease (exo) activity of poll molecules remained. Therefore it is suggested that 5'--- 3' exo activity as well as pol beta activity are essential for repair synthesis of excision repair in eukaryotic cells. PMID- 2216762 TI - An 'equalized cDNA library' by the reassociation of short double-stranded cDNAs. AB - The total number of genes in higher organisms is estimated to be under one hundred thousand. However, constructing a cDNA library containing a full set of genes expressed throughout the life time of an organism, without redundancy, is a major challenge for modern biology. Towards this goal, I have tried to make a library of mouse fibroblastoid Ltk- cells with nearly equal representations of cDNA clones. Double-stranded cDNAs (ds-cDNAs) are synthesized from mRNA using an oligo(dT)-Notl primer. After shearing to 200-400 bp, a synthetic linker-primer, which has one blunt and one sticky end and an internal EcoRl site, is ligated to the cDNAs. The cDNAs are amplified by the polymerase chain reaction (PCR) using the ligated linker-primer sequence. After denaturation and reassociation of the ds-cDNAs, and isolation of single-stranded cDNAs (ss-cDNAs) by hydroxylapatite chromatography, the ss-cDNAs are again amplified by PCR. The cDNAs are digested with EcoRl and Notl, and inserted into a plasmid vector. Colony hybridization with eight probes of different abundance showed a reduction in 'abundance variation' from at least 20,000-fold in the original library to 40-fold in the library constructed after three cycles of equalization. This indicates the usefulness of the current procedure for making equalized cDNA libraries. PMID- 2216763 TI - A single-stranded DNA-binding protein promotes the binding of the purified oestrogen receptor to its responsive element. AB - The purified human oestrogen receptor (hER) does not form a detectable complex with an oestrogen responsive element (ERE) under conditions where hER-ERE complexes are readily formed with crude extracts from Hela or yeast cells expressing the hER. This indicates that other factor(s) are necessary for ER-ERE binding. Such a ER DNA binding stimulatory factor (DBSF) has been purified from the yeast Saccharomyces cerevisiae. It is a 45 kDa single-stranded DNA-binding protein (SSB) which cannot be substituted for by the purified E. coli SSB. PMID- 2216764 TI - The binding site for the liver-specific transcription factor Tf-LF1 and the TATA box of the human transferrin gene promoter are the only elements necessary to direct liver-specific transcription in vitro. AB - We have studied the liver-specific transcriptional activity of the human transferrin gene promoter. Results of competition experiments, site-directed mutagenesis, and 5' deletion analysis have demonstrated that a TATA box and a binding site for the liver-specific protein Tf-LF1 are the only elements needed to direct hepatic-specific transcription in vitro. Thus, Tf-LF1 behaves as other previously described proteins, HNF-1, DBP and LF-A1, in that it is sufficient to confer liver-specific transcriptional activity to a promoter in vitro. This results contrast with observations made in transient expression experiments, in which Tf-LF1 binding alone cannot direct hepatic-specific expression, and the binding of at least one more protein, similar to C/EBP, is needed. Thus, as described for other hepatic genes, the number of elements necessary to confer tissue specificity is different in vivo and in vitro. PMID- 2216765 TI - Expression of a human O6-alkylguanine-DNA-alkyltransferase cDNA in human cells and transgenic mice. AB - A truncated human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA was ligated into an expression vector under the control of the mouse metallothionein-1 gene promotor and upstream of part of the human growth hormone gene to provide splice and polyadenylation signals. Transfection of this construct into human cells resulted in very high levels of ATase expression (more than 300 fmoles/mg protein versus less than 2 fm/mg protein in parent vector transfected control cells). Microinjection of a 4.2 kb fragment of this vector into B6D2F2 mouse embryos and implantation of survivors into pseudopregnant females has so far generated 35 offspring. Southern analysis of tail tip DNA has shown that 11 of the offspring are transgenic for the human ATase gene, between 1 and at least 30 copies of the gene being detected. Human ATase transcripts were detected in total RNA extracted from liver obtained from two male transgenic mice by partial hepatectomy. Cell free extracts of liver samples from five transgenic mice showed up to 4 times higher ATase levels than control livers. PMID- 2216766 TI - Synthesis and characterization of oligodeoxynucleotides containing the mutagenic base analogue 4-O-ethylthymine. AB - A method for the preparation of oligonucleotides containing the mutagenic base 4 O-ethylthymine is described for the first time. Use of p-nitrophenylethyl type base protecting groups together with phosphitetriester solid-phase methodology makes possible the rapid and efficient preparation of oligonucleotides bearing 4 O-ethylthymine, while standard base protecting groups are not compatible with the presence of this base. Possible applications of this methodology are discussed. PMID- 2216767 TI - Sequence specificity of the human mRNA N6-adenosine methylase in vitro. AB - N6-adenosine methylation is a frequent modification of mRNAs and their precursors, but little is known about the mechanism of the reaction or the function of the modification. To explore these questions, we developed conditions to examine N6-adenosine methylase activity in HeLa cell nuclear extracts. Transfer of the methyl group from S-[3H methyl]-adenosylmethionine to unlabeled random copolymer RNA substrates of varying ribonucleotide composition revealed a substrate specificity consistent with a previously deduced consensus sequence, Pu[G greater than A]AC[A/C/U]. 32-P labeled RNA substrates of defined sequence were used to examine the minimum sequence requirements for methylation. Each RNA was 20 nucleotides long, and contained either the core consensus sequence GGACU, or some variation of this sequence. RNAs containing GGACU, either in single or multiple copies, were good substrates for methylation, whereas RNAs containing single base substitutions within the GGACU sequence gave dramatically reduced methylation. These results demonstrate that the N6-adenosine methylase has a strict sequence specificity, and that there is no requirement for extended sequences or secondary structures for methylation. Recognition of this sequence does not require an RNA component, as micrococcal nuclease pretreatment of nuclear extracts actually increased methylation efficiency. PMID- 2216768 TI - Thermodynamics of triple helix formation: spectrophotometric studies on the d(A)10.2d(T)10 and d(C+3T4C+3).d(G3A4G3).d(C3T4C3) triple helices. AB - We have stabilized the d(A)10.2d(T)10 and d(C+LT4C+3).d(G3A4G3).d(C3T4C3) triple helices with either NaCl or MgCl2 at pH 5.5. UV mixing curves demonstrate a 1:2 stoichiometry of purine to pyrimidine strands under the appropriate conditions of pH and ionic strength. Circular dichroic titrations suggest a possible sequence independent spectral signature for triplex formation. Thermal denaturation profiles indicate the initial loss of the third strand followed by dissociation of the underlying duplex with increasing temperature. Depending on the base sequence and ionic conditions, the binding affinity of the third strand for the duplex at 25 degrees C is two to five orders of magnitude lower than that of the two strands forming the duplex. Thermodynamic parameters for triplex formation were determined for both sequences in the presence of 50 mM MgCl2 and/or 2.0 M NaCl. Hoogsteen base pairs are 0.22-0.64 kcal/mole less stable than Watson-Crick base pairs, depending on ionic conditions and base composition. C+.G and T.A Hoogsteen base pairs appear to have similar stability in the presence of Mg2+ ions at low pH. PMID- 2216769 TI - Chromatin assembly on replicating DNA in vitro. AB - Replicating single-stranded DNA is preferentially assembled into chromatin in Xenopus egg extracts relative to non-replicating double-stranded DNA. We have examined the molecular basis of this phenomenon. Single-stranded DNA itself is not a favored template for nucleosome assembly in comparison to double-stranded DNA. Complementary strand synthesis is required for the rapid assembly of nucleosomes. We present evidence that the assembly of chromatin on replicating DNA is a two step phenomenon. The first step involves the replication of DNA and the assembly of an intermediate structure, the second step involves the sequestration of histones H2A/H2B onto DNA. Histones H2A/H2B are preferentially sequestered onto replicated DNA in comparison to non-replicated DNA incubated in the extract. PMID- 2216770 TI - Transcription of single-copy hybrid lacZ genes by T7 RNA polymerase in Escherichia coli: mRNA synthesis and degradation can be uncoupled from translation. AB - In Escherichia coli transcription of individual genes generally requires concomitant translation, and thus the decay of mRNAs cannot be studied without the complication of translation. Here we have used T7 RNA polymerase to transcribe in vivo lacZ genes carrying ribosome binding sites of variable efficiency. We show that neither cell viability nor growth rate is affected by the T7-driven transcription of these genes, provided that they are present as single chromosomal copy. Furthermore, transcription is now completely uncoupled from translation, allowing large amounts of even completely untranslated mRNAs to be synthesized. Taking advantage of these features, we discuss the influence of the frequency of translation upon the processing and degradation of the lac message. PMID- 2216771 TI - II-Q restriction endonucleases--new class of type II enzymes. AB - Unique restriction endonucleases Bpu 10l and Bsil have been isolated from Bacillus pumilas and Bacillus sphaericus, respectively. The recognition sequences and cleavage points of these enzymes have been determinated as 5'-CC1TNAGC-3'/3' GGANT1CG-5' for Bpu 10l and 5'-C1TCGTG-3'/3'-GAGCA1C-5' for Bsil. Restriction endonucleases Bpu 10l and Bsil represent a new class of enzymes which recognize non-palindromic nucleotide sequences and hydrolize DNA within the recognition sequence. Bpu 10l and Bsil recognition sequences may be regarded as quasipalindromic and the enzymes may be designated as type II-Q restriction endonucleases. PMID- 2216772 TI - HrpF, a human sequence-specific DNA-binding protein homologous to XrpFI, a Xenopus laevis oocyte transcription factor. AB - The identification in HeLa nuclei of a novel DNA-binding protein, designated HrpF, is presented. This factor recognizes and binds a sequence of the Xenopus laevis L14 ribosomal protein (r-p) gene promoter bound by the Xenopus r-p transcription factor I (XrpFI). We show here that XrpFI and HrpF share a conserved DNA-binding domain. We also present evidences suggesting that the two factors perform similar functions in the cell. We discuss the hypothesis that closely related factors might be involved in the control of rp-gene transcription in vertebrates. PMID- 2216773 TI - A 40 kilodalton rat liver nuclear protein binds specifically to apolipoprotein B mRNA around the RNA editing site. AB - Apolipoprotein (apo) B-48 mRNA is the product of RNA editing which consists of a C----U conversion changing a CAA codon encoding Gln-2153 in apoB-100 mRNA to a UAA stop codon in apoB-48 mRNA. In the adult rat, RNA editing occurs both in the small intestine and the liver. We have studied the ability of rat liver nuclear extracts to bind to synthetic apoB mRNA segments spanning the editing site. Using an RNA gel mobility shift assay, we found the sequence-specific binding of a protein(s) to a 65-nucleotide apoB-100 mRNA. UV crosslinking followed by T1 ribonuclease digestion and SDS-polyacrylamide gel electrophoresis demonstrated the formation of a 40 kDa protein-RNA complex when 32P-labeled apoB-100 mRNA was incubated with a rat liver nuclear extract but not with HeLa nuclear extract. Binding was specific for the sense strand of apoB mRNA, and was not demonstrated with single-stranded apoB DNA, or antisense apoB RNA. The complex also failed to form if SDS was present during the UV light exposure. Binding experiments using synthetic apoB mRNAs indicate that the 40 kDa protein would also bind to apoB-48 mRNA but not apoA-I, apoA-IV, apoC-II or apoE mRNA. Experiments using deletion mutants of apoB-100 mRNA indicate efficient binding of wildtype 65-nucleotide (W65), 40-nucleotide (W40) and 26-nucleotide (W26) apoB-100 mRNA segments, but not 10-nucleotide (or smaller) segments of apoB-100 mRNA to the 40 kDa protein. In contrast, two other regions of apoB-100 mRNA, B-5' (bases 1128-3003) and B-3' (bases 11310-11390), failed to bind to the protein. The 40 kDa sequence-specific binding protein in rat liver nuclear extract may play a role in apoB-100 mRNA editing. PMID- 2216774 TI - Translation of the Saccharomyces cerevisiae tcm1 gene in the absence of a 5' untranslated leader. AB - The role of eukaryotic 5'-untranslated messenger RNA leaders is not entirely clear, since they share little sequence similarity among each other. The importance of the leader in determining the efficiency of translation initiation was addressed here by examining the polyribosome distribution of several leader deletion alleles of the yeast tcm1 gene (coding for ribosomal protein L3). Shortening of this 22-nucleotide leader, or complete removal of it (the first nucleotide of the mRNA becoming the A of the translation initiation codon AUG) permitted translation, albeit reduced. Further deletion of as few as the first two nucleotides of the initiation codon leads to a substantial reduction in ribosome loading, which is compatible with inefficient initiation at the next downstream, out-of-frame, AUG triplet. A second measure of translation initiation was obtained by assaying qualitatively for the production of biologically active L3 protein using growth-resistance to trichodermin. This experiment indicates that ribosomes can recognize the correct initiation codon even in the complete absence of a leader. We conclude that the 5'-untranslated leader of the yeast tcm1 gene is not essential for accurate translation initiation, but enhances its efficiency. PMID- 2216775 TI - The mechanism of production of multiple mRNAs for human glycophorin A. AB - The major sialoglycoprotein in the human red cell surface membrane, glycophorin A is encoded by a single gene. However, this gene gives rise to three species of glycophorin A mRNA of sizes about 1.0, 1.7 and 2.8 kilobases in reticulocytes, foetal liver cells and erythroleukaemic K562 cells. In an investigation of how the three mRNAs originated, we showed by primer extension analysis that all three mRNAs in K562 cells had identical 5' termini and, by nucleotide sequencing of correlated cDNAs, that they had identical coding regions, except for the well known glycophorin AM-AN polymorphism. However, we found also by sequencing the cDNAs that the mRNAs apparently differed from each other in the lengths of their 3' untranslated regions. This was confirmed by Northern blot analysis which also provided evidence that the three mRNAs originated by use of different polyadenylation signals of which seven were found in the longest cDNA we analyzed. PMID- 2216776 TI - Non-radioactive labeling of RNA transcripts in vitro with the hapten digoxigenin (DIG); hybridization and ELISA-based detection. AB - We have developed a system for the enzymatic in vitro synthesis of non radioactively labeled RNA which is derivatized with the hapten digoxigenin (DIG). The labeling reaction as well as the conditions for hybridization and detection of hybrids by an antibody-conjugate and a coupled colour reaction were analyzed and adapted for high sensitivity and low background. In addition, data on the performance and sensitivity of digoxigenin-labeled RNA probes in Southern and Northern blots are presented. PMID- 2216778 TI - Computer prediction of the exon-intron structure of mammalian pre-mRNAs. AB - A novel approach to the problem of prediction of protein-coding regions is suggested. This approach combines the site prediction methods to predict splicing sites and the global coding region prediction methods to choose the best variant of spliced mRNA. One of the advantages of the suggested algorithm is that the resulting mRNA or protein sequence may then be immediately analyzed further. The true mRNA either coincides with the predicted one or ranks high in the list of variants. In the latter situation the predicted mRNA usually differs from the true one in only one or two of several exons. The combined approach allows the use of a priori information (e.g. the putative protein length or the number of exons). It is possible to use additional parameters not considered here, such as the preferred lengths of exons and introns, and particularly the preferred position of introns in the reading frame and the preferred codon position of exon termini. PMID- 2216777 TI - A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain. AB - Hepatic Nuclear Factor 1 (HNF1, also referred to as LFB1, HP1 or APF) is a liver specific transcription factor required for the expression of many hepatocyte specific genes. We report here the purification of this rat liver nuclear protein and the cloning of its cDNA using a PCR-derived approach. Seven independent clones reveal 3 alternative polyadenylation sites and a unique open reading frame. Both a motif homologous to the homeodomain and a distal dimerization domain are required for specific DNA binding. Sequence comparisons reveal several atypical features at key positions in the segment corresponding to helices III and IV of the Antaennapedia homeodomain as well as a potential 24 amino acid loop in place of the universal turn between helices II and III. Together with its property to dimerize in the presence or absence of DNA, these features place HNF1 as the prototype of a novel subclass of transcription factors distantly related to homeoproteins. PMID- 2216779 TI - Sequence of the TCR beta chain gene used by a T cell clone specific for the synthetic polymer, GAT. PMID- 2216780 TI - Nucleotide sequence of a gene from alkaliphilic Bacillus firmus RAB that is homologous to the fpg gene of Escherichia coli. PMID- 2216781 TI - cDNA cloning of ovine interleukin 2 by PCR. PMID- 2216782 TI - Complete nucleotide sequence of a gene coding for Aspergillus aculeatus cellulase (FI-CMCase). PMID- 2216783 TI - Nucleotide sequence of the virion protein gene of cacao yellow mosaic tymovirus. PMID- 2216784 TI - Nucleotide sequence of the envelope glycoprotein gene of a dengue-2 virus isolated during an epidemic of benign dengue fever in Tonga in 1974. PMID- 2216785 TI - Nucleotide sequence of a Ricinus communis 2S albumin precursor gene. PMID- 2216786 TI - Nucleotide sequence of the cDNA encoding L-histidine decarboxylase derived from human basophilic leukemia cell line, KU-812-F. PMID- 2216787 TI - Human nonsarcomeric 20,000 Da myosin regulatory light chain cDNA. PMID- 2216788 TI - Sequence of tRNA(Glu) and its genes from the chloroplast genome of Chlamydomonas reinhardtii. PMID- 2216789 TI - Nucleotide sequence of the arrestin-like 49 Kd protein gene of Drosophila miranda. PMID- 2216790 TI - Human N-cadherin: nucleotide and deduced amino acid sequence. PMID- 2216791 TI - Sequence of a histone H2A cDNA from parsley. PMID- 2216792 TI - Nucleotide sequence of rice waxy gene. PMID- 2216793 TI - The nucleotide sequence of gene 3 of the soybean chalcone synthase multigene family. PMID- 2216794 TI - Nucleotide sequence encoding the major glycoprotein (GP2) of rat pancreatic secretory (zymogen) granule membranes. PMID- 2216795 TI - PCR-aided DNaseI footprinting of single copy gene sequences in permeabilized cells. PMID- 2216796 TI - Transient expression of DNA after ballistic introduction into Drosophila embryos. PMID- 2216797 TI - An improved method for sequencing double stranded plasmid DNA from minipreps using DMSO and modified template preparation. PMID- 2216798 TI - Direct PCR from whole blood, without DNA extraction. PMID- 2216799 TI - Klenow polymerase is preferable to T4 polymerase in end-labeling reactions. PMID- 2216800 TI - High efficiency electroporation of ligated DNA into bacteria. PMID- 2216801 TI - Use of primer pools for specific gene amplification. PMID- 2216802 TI - Dinucleotide repeat polymorphism at the SIS locus. PMID- 2216803 TI - Dinucleotide repeat polymorphism at the D11S420 locus. PMID- 2216804 TI - Dinucleotide repeat polymorphism at the D11S35 locus. PMID- 2216805 TI - Sequence polymorphism in the human apoB gene at position 8344. PMID- 2216806 TI - Dinucleotide repeat polymorphism at the D21S168 locus. PMID- 2216808 TI - [99mTc-2-methoxy-isobutyl-isonitrile in the diagnosis of coronary heart disease: results of a multicenter study]. AB - A total of 226 patients was studied in a phase-III multicenter trial to compare the results of stress/rest 99mTc-MIBI with 201TI scintigraphy and/or coronary arteriography. The evaluation of planar and SPECT imaging was based on a semiquantitative visual scoring. A congruent diagnosis was generated from all planar 201TI and 99mTc-MIBI scintigrams performed in 36 patients. In 62 of 63 patients, SPECT-studies with 99mTc-MIBI and 201TI led to an identical diagnosis. In one patient a positive result was obtained with 201TI-SPECT whereas 99mTc-MIBI was negative. Segmental agreement for 1509 SPECT segments was 85.7%, for 554 planar segments it was 86.6%. In comparison to coronary arteriography, performed in 180 patients, the overall sensitivity for the correct diagnosis of coronary artery disease (CAD) was 86% for planar MIBI scintigraphy or 92% for MIBI-SPECT. Overall specificity was 100% for planar imaging and 57% for SPECT. The low specificity of MIBI-SPECT was probably due to high prevalence of CAD in this study population. In a subgroup of 43 patients, who underwent coronary angiography, identical results were found with 99mTc-MIBI and 201TI. Only one patient showed a positive scintigraphic result with both 99mTc-MIBI and 201TI without angiographically proven stenosis greater than 50% or prior myocardial infarction. Vessel sensitivities in stenosed coronary arteries (greater than 50% stenosis) were 54% for the LAD and 87% for the RCX/RCA areas with MIBI-SPECT, or 51% or 79% for planar scintigraphy, respectively. Vessel specificities for SPECT were 65% in the LAD or 52% in the RCX/RCA, or 90% or 83% in planar imaging.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216809 TI - [The role of radionuclide ventriculograms in determining the indications for valve replacement in chronic aortic valve insufficiency]. AB - Timing of aortic valve replacement (AVR) in chronic aortic regurgitation (AR) remains a difficult problem in clinical practice. Radionuclide ventriculography (RNV) yields information on the extent of valvular regurgitation, the enlargement and the systolic function of the left ventricle. A "well-timed" AVR is defined by 1) postoperative improvement of clinical symptoms, decrease in left ventricular end-diastolic volume (EDV) and normalization of ejection fraction (EF) as well as by 2) greater improvement under surgical therapy as compared to conservative management. In "too early" AVR the latter condition is not fulfilled, while in "too late" AVR the first condition is not accomplished. In this study 54 patients with chronic aortic incompetence were evaluated by RNV to see whether these three groups ("too early", "well timed", "too late" AVR, resp.) can be separated by the relation between EDV and regurgitant volume (RV), the level of the EDV and the clinical status. The examination was based on pre- and postoperative RNV studies as well as on follow-up studies. A good postoperative result can be expected in cases with a preoperative EDV/RV-ratio similar to that observed in 30 patients with AR in whom AVR was not indicated. In contrast, in the majority of those cases with an EDV/RV-ratio exceeding this normal range the postoperative outcome will be unsatisfactory. If the EDV/RV-ratio is normal, AVR should be performed in cases with an EDV exceeding 400 ml, while in cases with an EDV between 300-400 ml AVR is only indicated in the presence of additional symptoms (NYHA greater than or equal to II).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216810 TI - 201Tl myocardial SPECT and beta-endorphin levels in patients with suspected silent ischemia. AB - Today silent myocardial ischemia (SMI) is a well-recognized phenomenon. However, in the absence of clinical signs suggesting coronary artery disease (CAD), a streamlined diagnostic approach for precise clarification has proved to be difficult. Sensitivity and specificity of ergometric results are rather poor in symptom-free patients. Thus the question arises, whether the necessity of coronary angiography can be established more precisely by 201Tl myocardial SPECT in these patients. Treadmill exercise according to the Bruce protocol, 201Tl myocardial SPECT and coronary angiography were performed in a total of 106 patients with suspected SMI. In group I (high probability of ischemia; n = 46), reversible defects detected by SPECT correlated well with significant stenoses and irreversible defects with subtotal stenoses or complete occlusions. SPECT sensitivity in the detection of ischemia was 91%, its specificity 96%. In group II (low probability of ischemia; n = 60), SPECT sensitivity was as high as in group I (94%) but due to a high number of false-positive results (e.g. cardiomyopathy) specificity was only 75%. However, SPECT was superior to exercise ECG (sensitivity 70%; specificity 56%) in the detection of SMI. In addition, beta endorphin levels were determined in 180 healthy subjects, 37 patients with symptomatic CAD and in 34 patients with SMI before and during maximum exercise. Exercise values in patients with SMI were significantly higher than in healthy subjects or in patients with symptomatic CAD. PMID- 2216811 TI - [Results of radioiodine therapy of manifest hyperthyroidism and autonomous struma with euthyroidism]. AB - In 200 patients follow-up examinations were performed up to one year after radioiodine therapy (RITh) with individual dose calculation. The mean applied dose was significantly lower in patients with immunogenic hyperthyroidism (Graves' disease) as compared to patients with non-immunogenic hyperthyroidism (disseminated/multifocal autonomy, HYDA). In Graves' disease the rate of recurrent hyperthyroidism was significantly higher and that of posttreatment hypothyroidism lower. Considering the high recurrence rate in Graves' disease a higher dose, e.g. 150 Gy, seems to be appropriate. In patients with HYDA who received antithyroid drugs during RITh, recurrence of hyperthyroidism appeared slightly more, and posttreatment hypothyroidism slightly less, frequent. The efficiency of RITh was not significantly reduced by additional treatment with antithyroid drugs. Posttreatment hypothyroidism in patients with euthyroid goiter and disseminated/multifocal autonomy (EUDA) occurred significantly more frequent if the basal TSH level was greater than or equal to 0.5 muIE/ml before therapy. The goiter size was reduced independent of the basal TSH level. In this group protection by thyroxine could avoid posttreatment hypothyroidism without impairing the reduction of goiter. In HYDA patients after thyroid surgery recurrence appeared less, and in those with EUDA posttreatment hypothyroidism significantly more, frequent. A lower dose seems to be suitable in patients who underwent thyroid surgery before. In patients with focal autonomy after RITh no recurrence of hyperthyroidism was observed. In 9% a suppressed basal TSHh level indicating persistent autonomy was seen. Posttreatment hypothyroidism in focal autonomy appeared only in patients without manifest hyperthyroidism before RITh and was significantly more frequent in this group as compared to the other groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216812 TI - [Scintigraphy using 111In-labeled antimyosin in Churg-Strauss vasculitis with myocardial involvement]. AB - A case of Churg-Strauss vasculitis in a young woman is reported. Diagnosis was confirmed by muscle biopsy. Affection of lungs, kidneys and skin was evident. In addition, myocarditis was suspected on clinical evidence. A highly positive scintigraphy with 111In-antimyosin enabled diagnosis and assessment of damage to the myocytes. With a heart-to-lung ratio of 3.0 the accumulated activity in the myocardium was higher than usually found in myocarditis. This finding supports the hypothesis of an additional ischemic necrosis. PMID- 2216807 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2216813 TI - [Immunoscintigraphy of the hematopoietic bone marrow in osteomyelofibrosis]. AB - In planning the treatment of splenomegaly in primary or secondary osteomyelofibrosis it is necessary to know whether there is any significant hematopoiesis outside the spleen. In contrast to the measurement of iron kinetics with 59Fe, which is not suitable for imaging, immunoscintigraphy with the monoclonal antibody Bw 250/183 allows specific imaging of the hematopoietic bone marrow. The diagnostic use of this method in addition to iron kinetics is illustrated and discussed in a patient with primary osteomyelofibrosis. PMID- 2216814 TI - Chips with everything. PMID- 2216816 TI - Nursing Poland's future. PMID- 2216815 TI - Casualty encounters. PMID- 2216817 TI - Alternative questions. PMID- 2216818 TI - Monitor and evaluate. PMID- 2216819 TI - Green gauges. PMID- 2216820 TI - No way to leave. PMID- 2216821 TI - Shift work. Beat the clock. PMID- 2216822 TI - Shift work. Planning shift patterns. PMID- 2216823 TI - Reducing stress in the cancer ward. PMID- 2216824 TI - Music as therapy. PMID- 2216825 TI - Mental handicap. Adopting the family approach. PMID- 2216827 TI - Comic relief. Interview by Daloni Carlisle. PMID- 2216826 TI - Going Dutch. PMID- 2216828 TI - How to state your case. PMID- 2216829 TI - Nurse-managed care in a rehabilitation ward. PMID- 2216830 TI - Warning over HIV home testing kits. PMID- 2216831 TI - Keeping leg ulcers moist. PMID- 2216832 TI - Eusol and the law. PMID- 2216834 TI - Refuge and respite. PMID- 2216833 TI - Pressure sore practices. PMID- 2216835 TI - Save the children. PMID- 2216836 TI - Moral imperatives. PMID- 2216838 TI - Just a little amputation. PMID- 2216837 TI - Breathing easily. PMID- 2216839 TI - Eastern Europe. After the revolution. PMID- 2216840 TI - Eastern Europe. Gaining respect. PMID- 2216841 TI - Eastern Europe. Changing associations. PMID- 2216842 TI - Racism in nursing. Biting the hand. PMID- 2216843 TI - Sharing the pain of motherhood. PMID- 2216844 TI - Turning the tide. PMID- 2216846 TI - Responsibility without authority. PMID- 2216847 TI - Day case. Eye surgery. PMID- 2216845 TI - Community nursing. Gathering information from the field. PMID- 2216848 TI - Mental handicap. Evaluating the family approach. PMID- 2216851 TI - Mental health. Training to meet the new agenda. PMID- 2216850 TI - Mental health. Approaches to cultural awareness. PMID- 2216849 TI - Mental health. Caught between two cultures. PMID- 2216853 TI - Delivering equality. PMID- 2216852 TI - Mental health. A dying breed? PMID- 2216854 TI - Standing up for Pink. PMID- 2216855 TI - Happy anniversary? PMID- 2216856 TI - Aiding ignorance? PMID- 2216857 TI - The danger hours. PMID- 2216858 TI - A noble vocation. PMID- 2216859 TI - Homes fit for nurses? PMID- 2216860 TI - Bequeath, bury or burn? PMID- 2216861 TI - Taking the waters. PMID- 2216862 TI - Matching staff to patient dependency. PMID- 2216863 TI - A return to the medical model? PMID- 2216864 TI - Community nursing. Striving for fairer workloads. PMID- 2216865 TI - Looking death in the face. PMID- 2216866 TI - Shifting the blame. PMID- 2216867 TI - Increased violence in an acute psychiatric ward. PMID- 2216868 TI - Nurses' attitudes to patients with AIDS. PMID- 2216869 TI - Clinical problem-solving behaviour. PMID- 2216871 TI - How to ... review an article. PMID- 2216870 TI - Nurse education. Teachers in the firing line. PMID- 2216872 TI - Theatre nursing. New priorities. PMID- 2216873 TI - Theatre nursing. The process of change. PMID- 2216874 TI - Teamwork in the theatre. PMID- 2216875 TI - The lessons from Stepping Hill. PMID- 2216877 TI - Fighting for equality. PMID- 2216876 TI - GP takeover? PMID- 2216878 TI - Growing up in smoke. PMID- 2216879 TI - Low birthweight babies. Monitoring child development. PMID- 2216880 TI - Low birthweight babies. Testing neonatal care. PMID- 2216881 TI - If the cap fits. PMID- 2216883 TI - Why perpetuate the shaving ritual? PMID- 2216882 TI - Eastern Europe: children's haven. Interview by Joanna Trevelyan. PMID- 2216884 TI - Adopting the hospice ethic. PMID- 2216885 TI - The human face of genetics. PMID- 2216887 TI - Don't worry--it's only cancer. PMID- 2216886 TI - Nursing development units: a virtue in uniformity? PMID- 2216888 TI - Shared care for diabetes between hospital and GPs. PMID- 2216890 TI - Using experiential teaching methods. PMID- 2216889 TI - Nurses' knowledge of coma assessment. PMID- 2216891 TI - Snap decisions. PMID- 2216892 TI - The Brussels Nightingale. PMID- 2216893 TI - Computers. Taking care of clerical work. PMID- 2216894 TI - Computers. An Oscar winner. PMID- 2216895 TI - Computers. Square pegs into round holes. PMID- 2216896 TI - Influence of dietary fats and vitamin E on plasma and hepatic vitamin A and beta carotene levels in rats fed excess beta-carotene. AB - Effects of different dietary lipids and excess vitamin E on plasma and hepatic concentrations of beta-carotene were evaluated in rats fed diets containing a large excess (0.2%) of beta-carotene. Male weanling Wistar Kyoto rats were fed beta-carotene-supplemented diets containing various dietary lipids as follows: Group I, a saturated fat (coconut oil); Group II, a monounsaturated fat (olive oil); Group III, a polyunsaturated fat rich in omega-6 fatty acids (safflower oil); Group IV, same as Group III plus vitamin E; and Group V, a polyunsaturated fat rich in omega-3 fatty acids (menhaden oil). All diets contained 2% safflower oil to provide sufficient amounts of linoleic acid (an essential fatty acid). Rats were killed after six weeks of feeding the various diets, and the concentrations of beta-carotene and vitamin A were determined in plasma and liver. Plasma vitamin A levels were not altered by any of the dietary lipids or by an excess of vitamin E. The concentrations of beta-carotene in plasma were the lowest in rats fed the diet containing menhaden oil. The feeding of the diet containing an excess of vitamin E also resulted in a significant decrease in plasma beta-carotene concentration. Similarly, the hepatic beta-carotene concentration was also reduced to about one-half in rats fed the diet containing an excess of vitamin E. Liver beta-carotene concentration was higher in Groups II and III than in the other three dietary groups. Hepatic vitamin A concentrations were also affected by the type of dietary fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216897 TI - Gastric lesions in rats fed salted food materials commonly eaten by Japanese. AB - A high intake of salted food is thought to be related to the high incidence of stomach cancer in Japan. In the present study, female F344 rats were divided into four groups. They were fed a nutritionally deficient purified diet (Group 1) and standard purified diet (Group 3) for 113 weeks and the same diets supplemented with salted cuttlefish guts, broiled, salted, dried sardines, pickled radish, and soy sauce (Groups 2 and 4). The incidence of papillomas and ulcers of the forestomach was highest in Group 4, which was given the standard diet supplemented with the salty food materials (p less than 0.05). These results suggest the importance of salted food as a suspicious causal factor in human stomach cancer in Japan. PMID- 2216900 TI - Prevention of melanoma. PMID- 2216898 TI - A case-control study of serum vitamins A, E, and C in lung cancer patients. AB - In a case-control study, serum levels of vitamins E, C, and A, carotenoids, total cholesterol, and retinol-binding protein along with smoking levels were studied on 59 persons newly diagnosed with lung cancer and also on matched hospitalized controls. The relative risk for smoking increased with the number of pack years of cigarettes smoked. Cases had significantly lower serum levels of carotenoids, vitamin E, and total cholesterol. Adjustment for serum cholesterol levels diminished the case-control difference for serum carotenoid levels and reduced the case-control difference for serum vitamin E levels. The results indicate that serum vitamin E may also be associated with lung cancer, possibly to a greater degree than serum retinol (vitamin A) is associated with lung cancer. PMID- 2216899 TI - Differential effects of Ca2+ on proliferation of stomach, colonic, and pancreatic cancer cell lines in vitro. AB - Calcium intake inhibits growth of colon cancer in vivo, the mechanisms of which are not fully elucidated. The objective of this study was to determine whether Ca2+ directly affects the growth of colon cancer cells in vitro and to compare the effects of Ca2+ on the growth of several gastroenteropancreatic cancer cells, including mouse colon cancer (MC-26), human colon cancer (LoVo and WIDR), human gastric cancer (AGS and SII), and human pancreatic cancer (PANC-1 and MIA) cells. All tumor cell lines tested grew in medium containing low concentration (approx 0.16 mM) of Ca2+. Higher concentrations of Ca2+ significantly inhibited the growth of all three colon cancer cell lines tested but had no significant effect on proliferation of the stomach and pancreatic cancer cell lines. Growth of AGS cells, in the presence of 0.1 or 0.5 mM EGTA (resulting in the loss of the extracellular Ca2+) was similar to that observed in the absence of EGTA, indicating that AGS cells were relatively insensitive to loss of extracellular Ca2+. In the presence of TMB-8, an inhibitor of intracellular Ca2+ release, the growth of colonic cancer cell lines was inhibited in a dose-dependent manner, indicating that a minimum basal level of intracellular Ca2+ was required for continued proliferation of colon cancer cells. The stomach cancer cell lines (AGS) was once again less sensitive to the effects of TMB-8 than were the colon cancer cells, indicating an inherent difference in Ca2+ requirements and sensitivity to Ca2+ for growth of different gastroenteropancreatic cancer cells in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216901 TI - Protease inhibitor content of human dietary samples. AB - A large body of experimental work has revealed that protease inhibitors (PI) are highly effective suppressors of carcinogenesis. Little is known about the level of PI activity in the diet of the US population. In the present study, we assayed the levels of PI activity in dietary samples from 31 free-living subjects who saved duplicate portions of all foods consumed over two 24-hour periods, six months apart. The majority of samples (90%) contained detectable PI activity; 82% contained trypsin inhibitory activity; 61% contained chymotrypsin inhibitory activity. Of those samples containing chymotrypsin inhibitory activity, 87% also contained trypsin inhibitory activity. The median concentration of soluble chymotrypsin inhibitory activity present in these samples was 6.5 micrograms/g food (range 0-150 micrograms/g food), whereas the median concentration of soluble trypsin inhibitory activity was 14.5 micrograms/g food (range 0-465 micrograms/g food). We conclude that a) human diet samples contain both chymotrypsin and trypsin inhibitory activity, b) the levels of PI in some of these samples was similar to that found to be anticarcinogenic in animal studies, and c) due to the large within-subject variation in PI intake, assessment of long-term dietary intake in epidemiological studies will be necessary to accurately classify subjects according to PI intake. PMID- 2216902 TI - Potassium inhibition of DMH-induced small intestinal tumors in rats. AB - This is a preliminary report that shows that supplemental potassium partially prevents 1,2-dimethylhydrazine (DMH) induction of tumors of the small intestine in Sprague-Dawley rats. Male rats were injected weekly with 20 mg DMH/kg body wt for 20 weeks. Potassium chloride was provided in the drinking water one week before the first DMH treatment and was continued until sacrifice 14 weeks after the last DMH treatment. There were four groups of rats and they were identified as follows: DMH, DMH + K, K, and untreated control. Based on 24-hour food and water consumption data and food and water compositions, rats provided 0.5% potassium (from KCl in the drinking water) were ingesting 287.5 +/- 9.2 mg potassium per 24 hours (K/Na = 4.18) and the unsupplemented groups were ingesting 180.3 +/- 18.4 mg potassium per 24 hours (K/Na = 2.62). At sacrifice, the incidence of DMH-induced small intestinal tumors was significantly (p less than 0.05) reduced from 46% (6/13) in the DMH group to 6% (1/17) in the DMH + K group (p less than 0.05). The potassium supplement also significantly (p less than 0.05) reduced the cumulative small intestinal tumor incidence from 40% (8/20) in the DMH group to 5% (1/20) in the DMH + K group. The incidence of colon tumors and of zymbal gland tumors appeared to be reduced by the potassium supplement; however, these were not statistically significant observations (p greater than 0.05). Based on the complete blood count and other blood parameters measured, the level of potassium supplement used induced no apparent toxic effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216903 TI - On predicting the future of dentistry. PMID- 2216904 TI - Sealing efficacy of therapeutic varnishes used with silver amalgam restorations. AB - The sealing abilities of three therapeutic varnishes were compared with that of a conventional copal varnish in vitro under Tytin silver amalgam restorations. The therapeutic varnishes comprised two commercial fluoride varnishes and one experimental chlorhexidine-containing varnish. Leakage was traced using a basic fuchsin dye and was found to be considerable, particularly on root surfaces. The therapeutic varnishes performed as well as, and in some cases better than, the control. It is suggested that the use of preventive therapeutic varnishes in operative dentistry merits attention and further study. PMID- 2216905 TI - A comparison of accuracy in seating and gap formation for three inlay/onlay techniques. AB - The accuracy (fit) of MOD inlays of three brands of composite resin was determined by measuring the axial discrepancy (marginal opening in the approximal area). The axial discrepancy varied between 17 and 121 microns. Directly manufactured inlays were more accurate (axial discrepancy: 17-26 microns) than indirectly manufactured inlays (axial discrepancy: 40-121 microns). Inlays of a microfilled resin, SR-Isosit, were less accurate than inlays of two hybrid materials, Brilliant and Estilux Posterior C VS (axial discrepancy: 121 microns vs 44 and 41 microns respectively). There was a tendency for 24-hour-old inlays to be less accurate than 10-minute-old inlays. The formation of marginal gaps due to contraction of the resin cement was assessed in a light microscope on cemented single-surfaced inlays. Gaps were not formed when enamel margins were etched or dentin margins treated with a dentin-bonding agent of high efficacy. Gaps (2.4 5.6 micron) were formed, however, at untreated dentin margins and at margins treated with dentin-bonding agents of low efficacy. PMID- 2216906 TI - Microleakage of a new cavity varnish with a high-copper spherical amalgam alloy. AB - In a study in vitro Copalite and Barrier cavity varnishes were applied to the walls of class 1 prepared cavities before placing Tytin, a high-copper amalgam. Tests with 45Ca and autoradiographs showed that at six months only Copalite was effective in preventing microleakage. At one year neither Barrier nor Copalite was preventing leakage. PMID- 2216907 TI - An evaluation of marginal leakage of Class 2 combined amalgam-composite restorations. AB - Forty class 2 cavities were prepared in 20 permanent posterior teeth. In 20 cavities the gingival margin was placed in enamel and in the other 20 cavities in cementum. In every tooth one of the cavities was filled with composite and the other with a combined amalgam-composite restoration. Microleakage at the various interfaces was assessed by dye penetration. It was concluded that microleakage of the combined amalgam-composite restorations was significantly lower than that of the conventional composite restorations. PMID- 2216908 TI - The evaluation of materials: relationships between laboratory investigations and clinical studies. PMID- 2216909 TI - [Allergic alveolitis--present knowledge]. PMID- 2216910 TI - [Control of breathing in patients with mechanical disorders of the lung]. AB - 22 normal volunteers, 57 patients with obstructive changes and 34 with restrictive type changes were studied. The following parameters were analyzed: maximal inspiratory and expiratory pressures, occlusion pressure and components of the breathing pattern. The patients were divided according to the degree of airway resistance and fall of vital capacity. All patients compared with the healthy volunteers demonstrated higher minute ventilation, and a higher neuro muscular respiratory drive as shown by the VT/Ti index and occlusion pressure. The breathing pattern did not correlate significantly with the different abnormalities of respiratory function in the studied groups. In the patients with obstructive changes a weak correlation was found between the occlusion pressure and airway resistance. In patients with restrictive type changes a weak correlation between occlusion pressure, static and specific compliance was found. The occlusion pressure was a more specific parameter characterizing respiratory drive compared with the VT/Ti index. Disturbances of pulmonary mechanics have a small but significant effect on respiratory control. PMID- 2216911 TI - [Analysis of respiratory parameters before and after working in manual laborers at a tobacco factory]. AB - From the group of 102 workers of local cigarette factory 51 persons had a contact with tobacco leaves before fermentation and other 51 workers with after process of fermentation. Values of spirometric parameters before and after 8 hour lung occupational exposition to tobacco leaves were evaluated in both groups. Increase of obturation of both large and small airways was found after workshift. 31 of examined persons had more than 20% inferior values of FEV1, Raw and FEF 25/75. That hyperspasmatic reaction of bronchi was found both in subjects with signs of obturation and in persons with normal results in examination before workshift. This finding concerned mostly workers who inhaled dust of tobacco leaves prior to fermentation. PMID- 2216912 TI - [Pulmonary abscesses in material from tuberculosis and lung disease clinics of the Academy of Medicine in Gdansk]. AB - 47 patients with pulmonary abscesses were analysed. The type of bacteria cultured from the sputum, type of chemotherapy and clinical outcome were assessed. Most of the patients (34) were already treated prior to admission to the Department. Most often with doxycycline and gentamycin. The following organisms were cultured: Streptococcus viridans, Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Antibiotic therapy was always instituted according to the antibiogram. Most often amikacin and cefamandole was given. The mean duration of hospitalization was 48 days. 44% of the patients were fully cured, in 40% only an improvement was seen. 7 patients expired (16%)--all of these patients were addicted to alcohol or had malignancy. PMID- 2216913 TI - [Bronchial tuberculosis in bronchoscopic examinations]. AB - In 195 cases of pulmonary tuberculosis in 70% changes in the bronchi were found. They were either active (45%) or inactive (25%). In 10% of the cases severe changes were found, this percentage did not decrease in the past 15 years. Most often bronchial findings were seen in elder women. In 4 cases bronchial cancer was co-existent. Difficulties in differential diagnosis in such cases were underlined. PMID- 2216914 TI - [Bronchial tuberculosis in bronchoscopic material]. AB - A retrospective analysis of 14,461 patients examined at the Bronchological Unit in the years 1978-1988 was carried out in order to assess the incidence of bronchial tuberculosis confirmed histopathologically. 46 cases met the selection criteria (19 females, age range 21-75 years, mean 56.2 +/- 18.8. years, 27 males, age range 21-85 yrs, mean 50.0 +/- 17.4 yrs). Only in 22 patients acid fast bacilli were cultured. Analysis of endoscopical changes was carried out according to the Jaroszewicz-Krakowka classification. Most often diffuse inflammatory changes were seen. PMID- 2216915 TI - [Post-traumatic chylothorax]. AB - A case of post-traumatic chylothorax in a 84 year old man with ILD is presented. The chylothorax was successfully treated after 6 months, which was confirmed at post-mortem, during which a solitary plasmocytoma of the left kidney was also diagnosed. PMID- 2216916 TI - [Pulmonary aspergilloma caused by Aspergillus niger]. AB - The authors present a case report of a 66 year old male that was admitted due to pulmonary lesions with cavitation localized in the upper left lobe. In the cavity an abnormal mass could be seen. In the differential diagnosis malignancy and tuberculosis were excluded. Fungi were cultured from the bronchial washings and sputum. Their morphological characteristics allowed them to be typed as Aspergillus niger. Slides from the thick, mucoid, black sputum demonstrated typical forms of the fungus. Polarized microscopy demonstrated calcium oxalate crystals. The final diagnosis was pulmonary aspergilloma caused by A.niger complicating a pulmonary abscess in the course of a pneumonia. PMID- 2216917 TI - [The role of airway infections in bronchial provocation reactions]. PMID- 2216918 TI - Predictive value of visible lesions (cheeks, lips, oropharynx) in suspected caustic ingestion: may endoscopy reasonably be omitted in completely negative pediatric patients? AB - The relationship between absence or presence of grossly visible lesions in the cheeks, lips, and oropharynx (C.L.O. burns) and the incidence, site, and degree of visceral burns was evaluated in all children referred to our hospital for a suspected caustic ingestion during a 10-year period. All children underwent eso gastro-duodenoscopy within 24 hours. Of the 156 children, 96 (61.6%) showed no visible signs of contact with the caustic substance; however, in 36/96 (37.5%), endoscopy revealed burns in one or more visceral sites. Eight of 36 children (22.2%) sustained potentially dangerous lesions (second to third degree). Sixty of 156 children (38.4%) showed visible lesions; in 30/60 (50%), endoscopy revealed other burns in one or more visceral sites. Fourteen of 30 patients (46.6%) sustained potentially dangerous lesions (second to third degree). A total of 50 esophageal burns have been recorded: first degree (E1), 32; second degree (E2), 12; third degree (E3), 6. Two of 12 patients with E2 lesions and 6/6 with E3 lesions developed esophageal stenosis. One patient in this latter group died because of complications related to a tracheostomy. A total of 31 gastric burns have been recorded: G1 (22), G2 (6), G3 (3). One gastric perforation was observed in the G3 group, whereas the remaining two lesions healed with residual asymptomatic scarring. Minimal scarring was observed in two of six patients with G2 burns. A total of eight lesions have been recorded in the larynx [L1 (3), L3 (1)] and in the duodenum [D1 (2), D2 (2)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216919 TI - Acute respiratory infections during the first three months of life: clinical, radiologic and physiologic predictors of etiology. AB - The usefulness of clinical, radiologic, and physiologic characteristics to identify pathogens was assessed in 90 infants aged two through 12 weeks, presenting to an outpatient clinic with an acute respiratory infection. Eighty four cases had cultures or rapid diagnostic tests for RSV, of which 25 were positive. Eighty-two infants had cultures or rapid diagnostic tests for Chlamydia, of which 16 were positive. Additional respiratory pathogens identified included parainfluenza (6 cases), rhinovirus (3 cases), pertussis (2 cases), and CMV (1 case). Multiple pathogens were identified in four cases: Chlamydia and RSV (2 cases), Chlamydia and parainfluenza (1 case), and Chlamydia and CMV (1 case). Clinical characteristics other than the need for hospitalization were not useful predictors of specific pathogens. X-rays were obtained in 20 (80%) of the RSV infections, 13 (81%) of the Chlamydia infections, six of the parainfluenza infections, two pertussis infections, and 25 cases without identification of the pathogen. X-ray findings could not distinguish between patients with or without a pathogen or between the pathogens. Severe findings were present in 28% (11/40) of cases with a pathogen identified, compared to 12% (3/26) of cases without a pathogen identified (NS). Moderate findings were present in 58% (23/40) of cases with a pathogen identified compared to 62% (16/26) of cases without a pathogen identified. Slight/negative findings were present in 15% (6/40) of cases with a pathogen identified, compared to 27% (7/26) of cases without a pathogen identified. Pulse oximetry was done in 30 cases, 22 of which had a pathogen identified (RSV 14, Chlamydia 7, pertussis 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216920 TI - Poor compliance with universal precautions: a universal phenomenon? AB - An anonymous survey was conducted in order to examine compliance with universal precautions in the Department of Pediatrics at Loyola University Medical Center in Maywood, Illinois. Completed questionnaires were returned by 23 faculty members, 29 residents, and 22 medical students. Gloves were worn consistently during venipuncture or intravenous catheterization by 13, 7, and 18% of attending physicians, residents, and students, respectively. Most physicians wear gloves only occasionally and cite presence of high-risk factors as their selection criterion. Interference with the performance of procedures is the most common cause of noncompliance. In view of poor compliance with universal precautions, further efforts are needed in order to decrease the incidence of preventable exposure to blood-borne infections. PMID- 2216921 TI - Rapid intravenous rehydration in the pediatric emergency department. AB - Children suffering from mild to moderate (3 to 6%) dehydration likely caused by viral gastroenteritis are often hospitalized because they are unable to tolerate oral fluids. We studied 17 such children, aged one to six years, who were otherwise healthy. All had isonatremic dehydration and were treated with 30 ml/kg of 3.3% dextrose and 0.3% saline over a period of three hours in the emergency department before being discharged. No patient required admission to the hospital. Only one patient required another course of rapid intravenous rehydration and subsequently improved without hospitalization. Although all our patients experienced vomiting before treatment, 65% had no vomiting after treatment. Rapid intravenous rehydration is an effective treatment, for children with mild to moderate dehydration secondary to presumed viral gastroenteritis, that obviates the need for hospitalization. PMID- 2216922 TI - Status epilepticus following the oral ingestion of cocaine in an infant. PMID- 2216923 TI - Absent or minimal cerebrospinal fluid abnormalities in Haemophilus influenzae meningitis. AB - A case of Haemophilus influenzae type b (Hib) meningitis in which the diagnosis and treatment were delayed because of normal cerebrospinal fluid analysis is presented. A retrospective review was conducted at two children's hospitals to determine the frequency and clinical characteristics of patients with Hib meningitis whose spinal fluid had a normal total white blood cell count, normal chemistries, and negative Gram stain, but subsequent growth of Hib in culture. Of 379 cases of Hib meningitis, two had completely normal CSF, and two had CSF containing small numbers of polymorphonuclear cells as the sole abnormality. In three of the four cases, the duration of symptoms was less than 24 hours, and appropriate therapy was significantly delayed because of benign-appearing CSF. Normal CSF cell counts, chemistries, and Gram stain do not exclude the possibility of bacterial meningitis, and one should remain suspicious when a child has clinical findings suggesting meningitis. PMID- 2216924 TI - Emergency intraosseous infusion in severely burned children. AB - Severely burned patients require rapid administration of large volumes of isotonic fluids. Obtaining adequate intravenous (IV) access in children with greater than 70% total body surface area burns may be difficult, time-consuming, and sometimes impossible. This report describes the use of intraosseous infusion technique as a life-saving means of establishing IV access in two severely burned children. PMID- 2216925 TI - Avulsion of the rectus femoris tendon: an unusual type of pelvic fracture. AB - We present the case of a 15-year-old boy evaluated in the emergency department after sustaining an acute hip injury during track and field practice. Pelvic radiograph demonstrated an avulsion fracture of the anterior inferior iliac spine. Review of the literature reveals this to be a well recognized, yet unusual and interesting injury. PMID- 2216926 TI - Pediatric HIV infection for the emergency physician: epidemiology and overview. PMID- 2216927 TI - What is a pediatric emergency physician? PMID- 2216928 TI - Abdominal trauma with hematuria. PMID- 2216929 TI - Outpatient management of burns in children. AB - The majority of burn wound management can be performed on an outpatient basis by the primary care physician or emergency physician. The physician, however, needs to know when to refer the patient for surgical evaluation and must be reasonably certain that the family will be compliant with wound care and follow-up. Fire prevention counselling still remains one of the most important aspects of burn management. PMID- 2216930 TI - Child-proof containers. PMID- 2216931 TI - Administration of succinylcholine via the intraosseous route. PMID- 2216932 TI - A case of bilateral radial head subluxation. PMID- 2216933 TI - [Effect of acute biliary pancreatitis on liver metabolism of phenazone]. AB - In 22 patients with acute pancreatitis caused by biliary calculi and 9 healthy controls the rate of hepatic elimination of phenazone was measured. The aim of the study was evaluation of the oxidative-detoxicating action of the liver in this disease in relation to its severity. In pancreatitis patients the half-time (T2) of phenazone was significantly (p less than 0.01 longer than in healthy subjects (23.6 +/- 10.5 vs 13.2 +/- 7.2 hrs). The T2 of phenazone was not correlated with the concentrations of transaminases, bilirubin and prothrombin, but was correlated positively with the concentration of hepatic lactic dehydrogenase (p less than 0.001). In the initial stage of pancreatitis the T2 of phenazone was without prognostic significance and showed no agreement with Ranson's clinical-laboratory classification of the severity of the disease. The degree of impairment of the hepatic metabolism of phenazone measured with the percent difference between T2 of phenazone in both tests was significantly (p less than 0.05) greater in the group of patients with complications than in those without pancreatitis complications (70.7 +/- 64.4% vs 21.4 +/- 16.2%). Biliary pancreatitis impairs the oxidative-reductive function of the liver proportionally to the degree of hepatic lactic dehydrogenase in the serum. Evaluation of the rate of hepatic elimination of phenazone in the initial stage of this pancreatitis was without prognostic importance for the severity of the disease. PMID- 2216934 TI - [Selected parameters of calcium and phosphate metabolism in patients after kidney transplantation and administration of azathioprine or cyclosporin A]. AB - The influence was studied of the type of immunosuppression on calciuria, phosphaturia, and on the levels of parathyroid hormone (PTH), calcitonin (CT), 25 hydroxycholecalciferol (25/OH/D), total calcium, magnesium, and alkaline phosphatase activity in 24 patients after renal transplantation. Twelve of these patients received cyclosporin with prednisone (group CyA) and other 12 were treated with azathioprine and prednisone (group Aza). Independently of the type of immunosuppression used, in both groups a significantly higher concentration of PTH, CT, 25/OH/D and greater activity of alkaline phosphatase were demonstrated in relation to healthy controls. In both studied groups the patients had also a significantly reduced calciuria and phosphatemia than controls. In group Aza the patients had a significantly lower phosphaturia and significantly higher magnesemia than in group CyA. The results of these investigations suggest a certain influence of the type of immunosuppression on the intensity of calcium phosphate metabolism in renal graft recipients. PMID- 2216935 TI - [Effect of physical exercise and heat on energy expenditure in obesity]. AB - The effect of exercise and thermal stress on energy expenditure was studied in obese and lean subjects. The group of obese subjects comprised 20 women with body weight 81-159 kg, and the control group included 12 lean women weighing 51-58 kg. The energy expenditure was assessed by the method of indirect calorimetry with a Spirolyt II apparatus. The heart rate, the systolic and diastolic pressure were measured. The tested subjects were subjected to a 60 W (60 J/s) exercise on a cycle ergometer during 10 minutes, and immediately after it they were exposed to hot air in a chamber at about 60 degrees for 30 min. On the following day this sequence was reversed, with exercise following heat exposure. In the obese women the energy expenditure at rest was 93.4 +/- 17.5 W, and during exposure to heat after exercise it was 124.0 +/- 21.3 W. During exercise preceded by heat exposure it was 436.3 +/- 51.6 W. In lean subjects the corresponding values were lower: 77.5 +/- 6.5 W, 104.0 +/- 14.8 W, 376.8 +/- 36.1 W. After calculation of energy expenditure per 1 m2 of body area this expenditure was, however, lower in the group of obese subjects. The exposure to physical exercise before thermal stress increased significantly the energy expenditure in relation to that caused by each of these exposures separately. The heart rate and the systolic and diastolic blood pressures were higher in obese subjects. In both groups thermal stress increased the heart rate and systolic pressure but decreased the diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2216936 TI - [Effect of adrenergic beta receptor blockaders and thiazide diuretics on gastric acid and gastrin secretion in patients with essential hypertension]. AB - The purpose of the study was to evaluate the effect of 6 weeks treatment with hydrochlorothiazide or propranolol on gastric acid and gastrin secretion in essential hypertension. The study was carried out in 10 patients receiving propranolol and 10 treated with hydrochlorothiazide. Acid and gastrin secretion were determined during histamine stimulation tests (Kay's test). Before the treatment the patients with essential hypertension were not significantly different from healthy controls with respect to acid secretion and gastrinemia profile after histamine stimulus. In both groups of patients no significant effect was observed of hypotensive treatment on basal acid output, but a significant inhibitory effect on gastrin secretion was noted. This effect was significantly greater in patients treated with propranolol than in the hydrochlorothiazide group. Moreover, in propranolol-treated patients a significant fall of histamine-induced acid secretion was found. PMID- 2216937 TI - [Cigarette smoking and pathophysiology of diseases of the digestive system--facts and hypotheses. I. Cigarette smoking and physiology of the digestive system]. PMID- 2216938 TI - [Activation and functions of blood platelets in patients with diabetes mellitus type 1 before and during the treatment with indobufen]. AB - In 18 patients with type I diabetes the effect was studied of 10 days of Indobufen administration in daily doses of 400 mg on the activation and function of platelets. Spontaneous and ADP and adrenaline-induced aggregation, adhesiveness, platelet factors 3 and 4, and generation of malonyldialdehyde (MDA) in platelets were investigated. The results were compared with similar results in the same group prior to the treatment and in a control group of 19 healthy subjects. Highly significant inhibition was noted of spontaneous inhibition and that evoked by adrenaline and ADP, and a considerable reduction of MDA generation by platelets. These results indicate that the new platelet inhibitor--Indobufen, effectively inhibiting platelet activation and function may prevent development of thrombotic complications of diabetes. PMID- 2216939 TI - [The role of free radicals in human pathology]. PMID- 2216940 TI - [Left-ventricular systolic time intervals in constrictive pericarditis. Effect of decortication and inspiration on the ejection time]. PMID- 2216941 TI - [Serum apolipoprotein B level and other parameters of lipid metabolism in patients after myocardial infarction]. AB - Total cholesterol, triglycerides, cholesterol HDL, and apolipoproteins B were determined in 117 patients including 87 patients with recent myocardial infarction. Cholesterol LDL was calculated from Friedewald-Frederickson 's equation. Calculated mean values of the above parameters of lipid metabolism were within normal values. In the group of patients with recent myocardial infarction the following subgroups were distinguished: male patients who under went myocardial infarction under 40 years of life (subgroup A), male patients who underwent myocardial infarction at the age over 40 years (subgroup B), and female patients (subgroup C). No statistically significant differences between male and female patients were noted. A sole lipid index differentiating subgroups A and B was serum apolipoprotein B level (1.5 g/L in subgroup A, and 1.16 g/L in subgroup B). Discrimination analysis has shown also a higher value of this parameter in distinguishing the subjects who underwent myocardial infarction in the young age. PMID- 2216942 TI - [Practical value of Frank's leads in electrocardiographic diagnosis of myocardial infarction]. AB - Authors' own modification of Frank's leads is discussed. Potentials from these leads are recorded simultaneously with routine ECG. Frank's leads are used to increase possibility to diagnose myocardial infarction. Proposed leads in x, y, z, axis of Frank system enable to differentiate pathological QS wave in chest V1 V3 leads between myocardial infarction of the anterior wall and detectable intraventricular potentials in patients with emphysema. A lack of physiologic Q wave in "z+"-lead always indicates anterior wall infarction. Pronounced Q wave of "infarctional" character in y-lead x-lead--in the lesions to the lateral wall. Pathologies present in the posterior wall infarction while from cal Q wave from "z+"-lead facilitates diagnosis of the posterior wall infarction. PMID- 2216943 TI - [Echo- and electrocardiography in myocardial infarction--accordance and discrepancies]. PMID- 2216944 TI - [Platelet aggregation in patients with coronary disease treated with nifedipine]. AB - The effect of nifedipine on the aggregation of blood platelets has been studied in patients with coronary heart disease. The study involved 78 males, aged between 36 and 64 years (mean age 51 years). The level of aggregation was evaluated before and after a single nifedipine dose of 10 mg (in 15 patients) and of 20 mg (in 34 patients) as well as before and after the treatment with nifedipine (of 29 patient) with a daily dose of 30 mg for two weeks. Aggregation of blood platelets induced by adenosine--diphosphate in of concentrations 1 microM/ml and of 5 microM/ml were estimated by the Born method. It was found that nifedipine reduces the aggregation of the blood platelets in patients with coronary heart disease following single and long-term treatment. PMID- 2216945 TI - [Etiological analysis of arrhythmia among sailors]. PMID- 2216946 TI - [Latent ischemic heart disease]. PMID- 2216948 TI - [Prospects of using calcium channel blockers in the treatment of alcoholism]. PMID- 2216947 TI - [Advances in pharmacotherapy of arteriosclerosis]. PMID- 2216949 TI - [Hypotensive effectiveness and metabolic effects of indapamide in patients with primary arterial hypertension]. AB - Indapamide--a non-thiazide diuretic agent--was given to 28 patients with mild and moderate hypertension in a daily dose of 2.5 mg for 12 weeks. Statistically significant decrease in both systolic and diastolic blood pressure and complete normalization of the arterial blood pressure were achieved in 82% of the treated patients. Adverse reactions were mild and transient. However, low but statistically significant decrease in blood serum potassium and changes in the carbohydrate metabolism were seen. No significant effect of the-drug on lipid metabolism was found except the low but statistically significant increase in total cholesterol. Indapamide is an efficient and well tolerated hypotensive agent. However, biochemical indices should be checked up during the treatment due to the potential adverse reactions. PMID- 2216950 TI - [Effectiveness of nifedipine in the treatment of arterial hypertension in various types of diabetes mellitus]. AB - Selection of indications and the general tactics of nifedipine monotherapy of hypertension in diabetic subjects is not clearly established, as yet. It refers specifically to different forms and phases of diabetes mellitus. This was the reason to carry out a respective study. In 4 groups of hypertension: 1) in diabetics without vascular complications, 2) in diabetic nephropathy, 3) in diabetics type II without nephropathy, and 4) in comparative group of subjects without diabetes mellitus, a 6-week controlled, open trial was performed. Before, during and after nifedipine (3 X 10-20 mg p.d.), the following parameters were monitored: 1) systolic, diastolic and mean blood pressures, 2) glycaemic indices of diabetes control, 3) serum cholesterol: total, HDL, LDL, triglycerides, 4) daily albuminuria and GFR, 5) adverse reactions to nifedipine. It could be concluded that nifedipine therapy was relatively most effective and safe in hypertensive diabetics type II without nephropathy. It was less effective in diabetics type I without nephropathy and failed in diabetics type I with nephropathy. PMID- 2216951 TI - [New thrombolytic drugs]. PMID- 2216952 TI - [Pharmacokinetics of phenazone in patients with fast and slow euthyroidism after methimazole treatment]. AB - Hyperthyroidic patients treated with methimazole were retrospectively divided into two groups, depending on the period of time required for euthyreosis: these attaining euthyreosis up to 28 days of therapy (A) and these in whom thyroid gland functioning is normalized after a 35-day therapy with full dose of methimazole (B). The study aimed at investigating whether clinical euthyreosis is related to the activity of microsomal enzymes in the liver using phenazone elimination test for this purpose. Phenazone elimination test was performed just before the treatment and after 8 weeks of methimazole administration. A decrease in kel and Clt as well as an increase in AUC were noted. These changes were more pronounced in patients of group A than those of group B. It might be concluded that phenazone pharmacokinetics is different in patients quickly attaining euthyreosis. The difference is probably due to the difference in biotransformation of methimazole in the liver in which microsomal enzymes play some role. PMID- 2216954 TI - [Interactions of antineoplastic agents with other drugs]. PMID- 2216953 TI - [Effect of disorders of thyroid function on phenazone pharmacokinetics]. AB - Phenazone elimination test, as a marker of metabolic efficiency of the liver, was carried out in 11 hypothyroid patients. 20 hyperthyroid patients, 10 persons after hyperthyroidism treatment and in 20 healthy persons as a control group. In hyperthyroid patients the acceleration, and in hypothyroid patients the delay of phenazone elimination, in comparison with a control group was observed. Moreover, the impairment of phenazone gastrointestinal absorption was shown in hypothyroid patients and in persons after hyperthyroidism treatment. Similar alterations may be expected in persons with thyroid dysfunctions to whom the drugs with pharmacokinetic properties similar to phenazone are administered. PMID- 2216955 TI - [Effect of liver diseases on pharmacokinetics of drugs]. PMID- 2216956 TI - [Progress in the field of peptide hormones through the eyes of an internist]. PMID- 2216958 TI - [The provocation test in children with cow-milk protein and gluten intolerance: evaluation of the clinical response and lesions in the mucous membrane of the small intestine]. AB - Provocation test (re-introduction of the noxious protein) was carried out in two groups of patients: (a) with intolerance to the cow-milk proteins (41 children) treated with milk-free diet for 6-24 months, and (b) with gluten intolerance (26 children) treated with gluten-free diet for 6-36 months. The following parameters were compared: type and frequency of the clinical symptoms seen in these patients prior to the introduction of allergen-free diet. Moreover, the type of observed morphological changes in the small intestine mucosa following provocation test were analysed in the groups of 7 patients. A two-year elimination of milk from the diet produces milk tolerance in about 61% patients; clinical symptoms in the remaining children are diversified. Re-introduction of gluten with the diet (provocation test) produces recurrence of gluten intolerance in 96% of children treated with gluten-free diet for 2-3 years. Recurrence of the disease was accompanied by the atrophy of the intestinal villi. PMID- 2216957 TI - [The effect of in vitro theophylline on T lymphocytes from patients with ulcers]. AB - An increase in the interest in the cellular immunity in patients with peptic and duodenal ulcers dates back to the detection of histamine H2 receptors on T-cells. In vitro effect of theophylline on T-cells in patients with peptic and duodenal ulcers was investigated. The experiment included 107 patients: 60 with peptic and duodenal ulcers and 47 controls. The experiment was carried out with theophylline test enabling to divide the whole population of T-cells forming active and "late" rosettes (ARCF and TRCF, respectively) into three subpopulations: theophylline resistant, theophylline-sensitive, and theophylline-dependent T-cells. Increased number of theophylline-dependent T-cells and significantly reduced baseline value of rosette-forming T-cells (p greater than .02) were found in patients with duodenal ulcer. Theophylline-dependent lymphocyte number was the highest in TREC rosette fraction in patients with duodenal ulcer. Statistically significant (p greater than .01; p greater than .05) and independent of patients' age tendency to an increase in the number of theophylline-sensitive T-cells in TRFC rosettes was seen in both peptic and duodenal ulcers. Theophylline-resistant lymphocytes ratio to theophylline-sensitive ones in TRFC rosettes was also significantly lower in patients with peptic ulcer. No correlation between these results and patients age was found in both the control group and patients with the ulcerative disease. An increase in theophylline-dependent T-cells in patients with duodenal ulcer suggests an increase in the number of immature forms of T-cells and indicate an important role of T-cells maturation disorders in the pathogenesis of duodenal ulcer. PMID- 2216959 TI - [Humoral response of the immunologic secretory system of the small intestine in children infected with Giardia intestinalis]. AB - Local humoral response of the intestinal mucosa was determined with secretory IgA levels and secretory component activity in enterocytes and duodenal content of 15 children infected with G. intestinalis. The obtained results were compared to those in 5 children with coeliac disease and 12 children with diarrhoea without lambliasis. Secretory IgA was increased in about 50% of children with lambliasis (in the remaining groups in 25% of children) to the values higher than that in the comparative groups. Secretory component activity was relatively high in the intestinal epithelium. Secretory component activity in the duodenal content was high in about 40% of children independently of the examined group. No correlation between the said variables was noted except positive correlation of secretory IgA levels and secretory component activity in the bile. PMID- 2216961 TI - [Leiomyosarcoma of the stomach and small intestine]. AB - Three cases of leiomyosarcoma are presented. The primary lesion to the stomach was seen in 2 patients while the small intestine in the remaining patient. Two patients underwent radical surgery. All patients were treated with multiple drug regimens. Radiotherapy was additionally carried out in one patient. One patient who underwent radical surgery and given maintaining chemotherapy is alive in the complete remission since 6 years while two remaining patients died within 3 and 6 years because of recurrence and haematopoietic proliferation. PMID- 2216960 TI - [Role of alcoholism in the development of upper gastrointestinal tumors]. AB - A preliminary report on the results of studies on the relationship between alcohol abuse and upper gastrointestinal tumours is presented. Alcohol abuse was measured with the aid of a questionnaire. GGTP and mean MCV were determined. Within the 1st September, 1986--30th September, 1987, 75 patients with the cancer of the upper gastrointestinal tract and 107 patients with benign lesions to this area were examined. Alcohol abuse was found in 33% of patients with the cancer and 19% of patients with benign lesions to the upper gastrointestinal tract. This difference is statistically significant (p greater than 0.05). The results of GGTP and MCV values were statistically insignificant in both groups. The authors have found more marked correlation of alcohol abuse with the cancer of the upper gastrointestinal tract in relation to the oral cavity and pharynx than the stomach. Further studies including larger groups of patients are recommended. PMID- 2216962 TI - [Long-term follow-up of a patient with early diagnosis of untreated stomach cancer]. AB - A case of the patient with type IIc carcinoma of the stomach is presented. The patient was followed-up for 7 years, and did not agree to the operation. Endoscopic examination has shown that the ulcer did not change within 6 years. No data suggesting generalization of the neoplastic process were available during 7 years following the diagnosis. The authors review the literature on the kinetics of the carcinoma of the stomach proliferation in both experimental and clinical investigations. PMID- 2216963 TI - [A rare case of colonic perforation in a sole site of latent lung cancer metastasis]. AB - A rare case of the perforation of the colon at the site of isolated micro-cancer of the lung in a 81-year old male is presented. A primary focus of the cancer was found during microscopic examination of the fibroserous mass collected from the apex of the right lung. The patient died because of the disseminated peritonitis. PMID- 2216964 TI - [Ormond's disease: difficulties with diagnosis and treatment]. AB - A case of a female patient is presented. The patient was treated for retroperitoneal fasciitis. An emphasis is on the diagnostic, differential, and therapeutic problems in this entity. Close cooperation of various specialists is needed in such a case. PMID- 2216965 TI - [Role of pancreatic peptides--neuropeptide Y, polypeptide YY and neurotensin, vasoactive intestinal peptide, and substance P in the body]. PMID- 2216966 TI - [Campylobacter pylori and its role in the pathogenesis of selected diseases of the stomach and duodenum]. PMID- 2216967 TI - [Esthetic improvement of the R.P.D. in mixed prosthodontics]. PMID- 2216968 TI - [Test of the efficacy of a plaque disclosing gel]. PMID- 2216969 TI - [The mandibular plane as an orientation plane in complete dentures. Computer assisted analysis]. PMID- 2216970 TI - Tony Pasquale's triumph. PMID- 2216971 TI - Vaginitis. Systematically solving a bothersome problem. AB - Vaginitis is a common cause of patient visits to primary care physicians. Causes include allergic and irritative factors and infectious agents. Diagnosis is readily made with use of simple office procedures such as wet smears, stains, and cultures. Treatment with appropriate antibiotics or vaginal preparations is usually effective. PMID- 2216972 TI - Hemolytic-uremic syndrome in children. A serious hazard of undercooked beef. AB - Hemolytic-uremic syndrome is the leading cause of acute renal failure in childhood. Its incidence in North America is increasing. Escherichia coli O157:H7 is the most common infectious trigger and is spread by contaminated beef products as well as from person to person. Antibiotics or antidiarrheal medications should not be used in the treatment of E coli hemorrhagic colitis or hemolytic-uremic syndrome. Mortality in children with the syndrome has fallen to less than 10% in North America, largely because of careful attention to nutrition, maintenance of a normal fluid and electrolyte balance, and careful monitoring. Education and emotional support of the family are important aspects of the treatment program. PMID- 2216974 TI - What if you are called to military service? PMID- 2216973 TI - Chest pain in teenagers. When is it significant? AB - Chest pain in teenagers often has no obvious organic cause. Onset of symptoms with an emotionally stressful situation may indicate psychogenic chest pain. The differential diagnosis also includes cardiac, musculoskeletal, gastrointestinal, and respiratory disorders. Routine testing generally does not help to establish a diagnosis and may even do harm by reinforcing a patient's unspoken fear of serious illness. Most teenagers with chest pain have no such illness, and symptoms usually resolve without therapy. An important role for primary care physicians is to provide support during evaluation and follow-up. PMID- 2216975 TI - Bell's palsy. Ensuring the best possible outcome. AB - Bell's palsy is thought to be an idiopathic polyneuritis and must be distinguished from other disorders that cause facial weakness. In most cases, differentiation can be accomplished on the basis of the history, physical examination, and clinical course. Routine follow-up care ensures that recovery is occurring. Electrodiagnostic testing often helps to assess prognosis. Eye care and corticosteroid therapy are recommended. PMID- 2216976 TI - Infectious diarrhea. Managing a misery that is still worldwide. AB - Infectious diarrhea is the largest single cause of morbidity and mortality in the world. Bacteria, viruses, and protozoan parasites are the most common causative agents. Treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration. Antimicrobial therapy is reserved for very ill patients only. With the exception of Cryptosporidium, for which no effective agent is yet available, all protozoan infections are treatable with metronidazole. PMID- 2216977 TI - Reactions to iodinated radiographic contrast agents. How to identify and manage patients at risk. AB - Systemic adverse reactions to iodinated radiographic contrast material are infrequent but can be dramatic. The number of patients experiencing such reactions can be minimized by selecting the most appropriate diagnostic study for each patient and by identifying patients at increased risk. Pretreatment with corticosteroids and use of low-osmolality contrast materials can minimize the number of severe reactions in high-risk patients. PMID- 2216978 TI - The infant with a reddish diaper. AB - The infant with a reddish diaper presents a diagnostic challenge to the primary care physician. As described by Dr Baumgardner, the cause may be benign, but more ominous disorders must be ruled out. PMID- 2216979 TI - Mood disorders. Is your primary care patient depressed? AB - Treatment of patients with mood disorder can be one of the most rewarding experiences in medicine. Optimal treatment is contingent on accurate diagnosis according to current criteria and terminology. Major depression needs further categorization in reference to atypical or psychotic features, seasonal aspects, melancholia, mania, or dysthymia. Most patients with major depression need pharmacotherapy, often in combination with psychotherapy. A number of therapeutic regimens using various antidepressant agents are available. PMID- 2216980 TI - Bacterial or viral meningitis? Measuring lactate in CSF can help you know quickly. AB - Measurement of cerebrospinal fluid (CSF) lactate is a useful test when properly applied to the appropriate clinical situation and can offer information other CSF parameters cannot provide. Except for Gram's stain of CSF, lactate level is the most important CSF parameter in the early differentiation of viral (aseptic) and bacterial purulent meningitis. PMID- 2216982 TI - Using the electric larynx to enable patients to communicate after tracheostomy. PMID- 2216981 TI - Two magic questions. PMID- 2216983 TI - Aluminum toxicity and Alzheimer's disease. Is there a connection? AB - Similarities between Alzheimer's disease and aluminum toxicity have led to the suggestion that a causal relationship may exist. However, the two disorders differ in many respects. The author reviews the evidence concerning the relationship between aluminum toxicity and Alzheimer's disease and answers the question, is there a connection? PMID- 2216984 TI - How to help your patient choose the right wheelchair. AB - For a disabled patient, a wheelchair can be the key to a more enjoyable, useful, and independent life--provided it is carefully chosen and suited to his or her needs. In this article, Dr Blocker describes how to decide when a wheelchair is needed and how to match the patient with the best chair. PMID- 2216985 TI - Understanding dizziness. How to decipher this nonspecific symptom. AB - Dizziness is a common but often nonspecific symptom. Through careful history taking and physical examination, primary care physicians can usually determine the type of sensation (vertigo or light-headedness) and its source. Although most causes of dizziness are benign, disorders of the central nervous system tend to be ominous and require immediate referral to a specialist. PMID- 2216986 TI - Thank you, Dr Heimlich. PMID- 2216987 TI - Healthcare crisis. As I see it. What would you do to close the checkbook on runaway healthcare costs? PMID- 2216988 TI - Clinical recognition and evaluation of peptic ulcer disease. AB - When a patient has epigastric pain that worsens 1 to 3 hours after meals, the possibility of peptic ulcer disease should be considered. Completely typical clinical presentations in patients younger than age 50 justify empirical therapy when no physical or laboratory findings suggest a mimicking disorder. Esophagogastroduodenoscopy should be undertaken when response to therapy is incomplete, symptoms recur quickly, or dyspeptic symptoms present for the first time in a patient older than age 50. When gastric ulcers are diagnosed radiographically, endoscopy and biopsy at multiple sites should be done to exclude malignant disease. Intractable duodenal ulcers may necessitate endoscopic biopsy of antral and duodenal mucosa to rule out an associated Helicobacter pylori infection, which may modify therapeutic approaches. Zollinger-Ellison syndrome is rare but should be suspected when ulcer disease presents atypically or aggressively or in families. Diagnosis is not difficult to confirm. PMID- 2216989 TI - Medical treatment and prevention of peptic ulcer disease. AB - Many agents seem to be equally effective for the treatment of peptic ulcer disease. This is true despite the drugs' varied mechanisms of action, and this observation has caused investigators to shift their focus from aggressive to defensive factors when studying ulcer pathogenesis. Patients with a healed ulcer are always at risk for recurrence, and guidelines are available for management of these patients. Ulcer prevention becomes a crucial issue in intensive care units where critically ill patients have many known risk factors. Maintaining a gastric pH above 4.0 appears to reduce the morbidity and mortality associated with such stress-induced ulcers. Use of nonsteroidal anti-inflammatory drugs increases ulcer risk and complications in the elderly, in women with rheumatoid arthritis, and in smokers and abusers of alcohol. Prophylaxis with the synthetic prostaglandin analogue misoprostol (Cytotec) appears to reduce this risk. PMID- 2216990 TI - New findings in treatment of colon cancer. AB - Patients with colon cancer involving regional lymph nodes (stage C disease) have a 5-year survival rate of only 30% to 40%, and the majority die of recurrent disease. Recent trials have shown increased survival rates with postoperative use of fluorouracil plus levamisole. The authors discuss these findings and the implications on treatment recommendations for stage C colon cancer. PMID- 2216991 TI - Initial management of trauma. The first 5 minutes. AB - Trauma is the leading cause of death in young Americans and is responsible for the loss of more productive years of life than heart disease and cancer combined. Initial management of trauma consists of the establishment or maintenance of a patent airway, ensurance of adequate breathing, and resuscitation of the circulation. All of these are accomplished simultaneously with a cursory survey to identify immediately life-threatening injuries and to prevent permanent disability. PMID- 2216992 TI - Initial management of trauma. The next 60 minutes. AB - If and when hemodynamic stability has been achieved in a trauma patient, a detailed physical examination and appropriate diagnostic studies are performed. The successful management of trauma demands that immediately life-threatening problems receive top priority and that patients be continuously reexamined and problems reprioritized as conditions change. Finally, it is imperative that appropriate surgical evaluation and treatment be undertaken as soon as possible. Trauma patients should not be allowed to languish or undergo extensive examination in a hospital lacking surgical or other specialists trained to treat the problems identified. Transfer to another facility, whether for specialized diagnostic tests or for evaluation and treatment by surgical specialists, should be accomplished as quickly as possible. PMID- 2216993 TI - Gastroenterology. PMID- 2216994 TI - Efficacy of enalapril in essential hypertension and its comparison with atenolol. AB - The effect of enalapril was evaluated in 67 patients with essential hypertension, and its therapeutic efficacy was compared with atenolol in a placebo run-in, single-blind, cross-over trial. Enalapril significantly reduced blood pressure in all grades of essential hypertension. As monotherapy it 'normalized' blood pressure in 88%, 50% and 25% of patients with mild, moderate and severe hypertension respectively. Optimal dose for most of the patients was 20 to 40 mg/day. Comparison with atenolol revealed almost parallel efficacy of the two drugs, although enalapril produced a significantly greater reduction in systolic blood pressure in patients with mild and moderate hypertension (P less than 0.01 in each group). No serious side effects were encountered with either drug. Enalapril, therefore, has a potent and slightly superior antihypertensive effect to that of atenolol, and may be used as a 'first-step' drug in the treatment of hypertensive patients. PMID- 2216996 TI - Facial nerve palsy associated with underwater barotrauma. AB - This report describes a case of facial nerve palsy following barotitis media sustained at shallow depth. The neuropraxia is likely to have been due to the direct effect of pressure, facilitated by a congenital hiatus in the bony canal protecting the facial nerve in the middle ear. PMID- 2216995 TI - A gastrectomy population: 25-30 years on. AB - Prior to 1960 a Polya gastrectomy was the most frequent operation for duodenal ulcer. The majority of these patients now have reached the age of sixty or older. A prospective longitudinal study of a cohort of patients who underwent gastrectomy between 1955 and 1960 was undertaken. Twenty five to thirty years later the study has revealed the extent of the nutritional problems that may arise with the passage of time and shows that these numerically far outweigh the mechanical post-gastrectomy syndromes and weight loss which tended to dominate the earlier post-gastrectomy scene. By the end of the first decade, iron deficiency was the commonest nutritional problem. Vitamin B12 deficiency assumed more importance in the second decade. During the third decade both reached equal prevalence, being found in some 90% of the female and 70% of the male residual population. Vitamin D deficiency and early osteomalacia was a lesser problem, reaching its climax in the second decade. Evidence suggested a high incidence of osteoporosis and this requires further investigation. Overall, women fared worse than men with a higher and earlier incidence of iron deficiency, particularly in the pre-menopausal group. This study emphasizes the increasing need for regular screening of post-gastrectomy patients to detect early iron, vitamin B12 and vitamin D deficiencies as patients grow older. PMID- 2216997 TI - Cat-scratch disease presenting as the oculoglandular syndrome of Parinaud: a report of two cases. PMID- 2216999 TI - Raised dopamine metabolites in a case of malignant paraganglioma. AB - This paper describes the case of a malignant retroperitoneal paraganglioma with extensive metastases. The patient presented with a supraclavicular mass and an absence of hypertension. Exclusively raised dopamine metabolites were detected which may be a marker of a malignant process and account for the lack of hypertension. PMID- 2216998 TI - Successful late treatment of venous air embolism with hyperbaric oxygen. AB - A case of haemodialysis-associated venous air embolism is described. The patient commenced hyperbaric oxygen therapy 21 hours after the event when, despite appearing decerebrate, he made a complete recovery. This case underlines the importance of all clinicians being aware of those centres with facilities for hyperbaric therapy and the need to refer all patients with cerebral air embolism even following a prolonged delay. PMID- 2217000 TI - Acquired von Willebrand's disease and hypothyroidism: report of a case presenting with menorrhagia. AB - A 17 year old woman presented with severe anaemia due to menorrhagia. On investigation, she was shown to have abnormalities of her haemostatic mechanism consistent with von Willebrand's disease Type I, although there was no family history of this disorder. In addition, she was shown to have severe primary hypothyroidism. On correction of hypothyroidism with oral thyroxine, her coagulation defects returned to normal and menorrhagia ceased. This is consistent with acquired von Willebrand's disease secondary to hypothyroidism. PMID- 2217003 TI - Conversation piece--the Voluntary Service Overseas Director. Interview by P. D. Welsby. PMID- 2217001 TI - Primary plasmacytoma of the thyroid. AB - Primary plasmacytoma of the thyroid is a very rare tumour. We report a case and emphasize the importance of excluding multiple myeloma which may present as an extramedullary plasmacytoma. Histological diagnosis has been simplified by the use of immunohistochemical techniques. PMID- 2217002 TI - Multiple Salmonella enteritidis leg abscesses in a patient with systemic lupus erythematosus. AB - We describe a 19 year old woman with systemic lupus erythematosus on corticosteroid therapy, who developed bilateral, multiple, gas-forming Salmonella enteritidis leg abscesses and osteomyelitis mimicking deep vein thrombosis. The infection was treated successfully by a combination of surgical drainage and intravenous ceftriaxone, followed by prolonged oral pefloxacin. This rare case of gas-producing S. enteritidis emphasizes the difficulty in diagnosing such complications in active systemic lupus erythematosus. PMID- 2217004 TI - Poisoning from Thevetia nerifolia (yellow oleander) PMID- 2217005 TI - Are we missing atypical bacterial meningitis in the elderly? PMID- 2217006 TI - The chronic fatigue syndrome: a return to common sense. PMID- 2217008 TI - Dipyridamole echocardiography: the bedside stress test for coronary artery disease. AB - Identification of dipyridamole-induced regional wall motion abnormalities by echocardiography has recently been proposed as an alternative diagnostic stress test for coronary artery disease. This study evaluates this new technique by comparing the results obtained (overall, regionally and by abnormality type) with those of thallium-201 myocardial imaging after dipyridamole stress in 25 patients. Acceptable echocardiograms were obtained in 20 patients (80%). Concordance of echocardiographic abnormalities for both overall and regional thallium abnormalities was 85%. Sensitivity, specificity and predictive value of dipyridamole echocardiography for overall and regional thallium defects were 92%, 71% and 85%, and 91%, 81% and 85% respectively. However, concordance between the two for abnormality type (i.e. ischaemia versus infarction) was only 66% and the sensitivity, specificity and predictive value of dipyridamole echocardiography for identifying ischaemia as opposed to infarction were only 43%, 82% and 63%, respectively. There was substantial agreement between thallium and echocardiographic imaging after dipyridamole infusion in the diagnosis of coronary artery disease. Echocardiography appears less well able to distinguish infarction from active ischaemia. Dipyridamole echocardiography provides a highly versatile, noninvasive bedside stress test for the detection and localization of coronary artery disease. PMID- 2217009 TI - Acanthosis nigricans in obese women with the polycystic ovary syndrome: disease spectrum not distinct entity. AB - Fasting and stimulated insulin concentrations in four patients with acanthosis nigricans and polycystic ovary syndrome were compared with four patients, matched for weight and ovarian morphology, without acanthosis. The median fasting serum insulin concentrations were 114.2 and 25.1 mU/l in the respective groups (P = 0.02). One additional patient was investigated before and after an 18% increase in weight which resulted in a 170% increase in fasting insulin concentrations and the development of acanthosis nigricans. These observations suggest that there is variation between individuals in the degree of obesity that results in the development of acanthosis and that obese patients with this skin condition represent the severe end of the spectrum of the polycystic ovary syndrome. PMID- 2217010 TI - An evaluation of combining thiopentone and etomidate for the induction of anaesthesia. AB - The characteristics of three combinations of thiopentone and etomidate [in the ratios of thiopentone (mg):etomidate (mg) of 5:1, 13:1 and 25:1] have been compared with the individual agents alone for the induction of anaesthesia. The incidence of pain on injection and abnormal movements was less with the combination containing the highest ratio of thiopentone to etomidate, when compared to etomidate alone. The mixtures did not otherwise confer any advantages over the individual agents. PMID- 2217011 TI - Analgesic nitrous oxide for alcohol withdrawal: a critical appraisal after 10 years' use. AB - We describe a method of treating the mild to moderate alcohol withdrawal state which has been used successfully for 10 years in over 7,000 cases. It is now the standard therapy at the largest dedicated alcoholic rehabilitation centre in Southern Africa. The technique uses analgesic (subanaesthetic) concentrations of nitrous oxide, which in most cases is administered on a single occasion for 20 minutes only. This results in the most rapid detoxification presently available, such that within an hour of the commencement of therapy the patient is so improved that they can eat the next ward meal. Provided the correct equipment and simple training is used this non-anaesthetic treatment is completely free of any serious side effects and the patient is at all times conscious and cooperative. Apart from this the amounts of sedative medication, such as benzodiazepines, are drastically reduced during detoxification. Because of the rapidity of the therapeutic response this technique is useful also as a screening test for assessing those patients requiring intensive therapy for the alcohol withdrawal state. There is evidence of the usefulness of analgesic nitrous oxide therapy for treating other addictive withdrawal states including opioid and nicotine. PMID- 2217013 TI - The history of sneezing. PMID- 2217012 TI - Venepuncture for calcium assays: should we still avoid the tourniquet? AB - Blood was collected by venepuncture from nine healthy subjects over a ten minute period before applying a standard tourniquet, and over a ten minute period afterwards. Plasma ionised calcium was unaltered by the tourniquet, whereas total calcium, total protein and albumin in serum increased modestly. However, there was no effect on total calcium adjusted for albumin. Even without albumin adjustment the change in total calcium was negligible within one minute of the application of the tourniquet. We consider that in ordinary clinical practice, there is no need to perform venepuncture for calcium assays without a tourniquet. PMID- 2217007 TI - Nephrology, dialysis and transplantation. PMID- 2217014 TI - Cerebellar syndrome with hydrocephalus due to Mycoplasma pneumoniae infection. AB - A 27 year old woman developed a cerebellar syndrome with serological evidence of recent Mycoplasma pneumoniae infection. The cranial computed tomographic scan showed effacement of the fourth ventricle, enhancement of the basal meninges and hydrocephalus affecting the lateral and third ventricles. Clinical and radiological recovery occurred over 5 weeks. We propose that this was a manifestation of immune-mediated encephalomyelitis induced by the infection rather than direct invasion of the central nervous system. PMID- 2217015 TI - Mefenamic acid-induced neutropenia and renal failure in elderly females with hypothyroidism. AB - We report mefenamic acid-induced non-oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected. PMID- 2217016 TI - Electrical shock sustained in pregnancy followed by placental abruption. AB - The case of a pregnant woman suffering a large placental abruption following electric shock at 32 weeks' gestation is reported. No other such cases have been published in the literature. PMID- 2217018 TI - Extrinsic duodenal obstruction and halitosis. AB - Two siblings with extrinsic duodenal obstruction caused by congenital peritoneal bands are reported. Attention is drawn to the unusual physical sign of halitosis as a presenting feature. It is suggested that this physical sign may be an indication for barium studies. PMID- 2217017 TI - Retinal periphlebitis in ulcerative colitis. AB - A man presented with unilateral visual blurring associated with bilateral retinal periphlebitis which was felt to be a complication of his biopsy-proven active ulcerative colitis. Retinal periphlebitis has been associated rarely with some forms of colitis but we can find no report of its occurrence in association with ulcerative colitis although other ocular inflammatory disorders are well recognized. PMID- 2217019 TI - An unusual case of adrenal cortical carcinoma. AB - We describe a case of non-functioning adrenal cortical carcinoma, which recurred 16 years after surgical adrenalectomy. In addition, the patient was successfully treated for two anatomically separate and histologically different, primary malignant tumours. This case highlights the importance of lifelong follow-up after apparently curative surgical excision of an adrenal tumour. PMID- 2217020 TI - Heparin-associated skin necrosis. AB - A case of skin necrosis at the sites of injection of subcutaneous heparin is described. The patient went on to develop heparin-induced thrombocytopenia and pulmonary embolism. Review of the previously described cases of heparin associated skin necrosis reveals that this sequence of events is not uncommon. PMID- 2217021 TI - Irradiation-induced penile angiosarcoma. AB - We report a case of angiosarcoma of the glans penis in a 77 year old male Caucasian. The tumour developed 18 years after a course of radiotherapy for a penile ulcer which was an intra-epidermal squamous carcinoma. The differential diagnosis and the concept of radiotherapy-induced angiosarcomas are discussed. PMID- 2217022 TI - Bilateral adrenal lymphoma presenting as Addison's disease. PMID- 2217023 TI - Loperamide related toxic megacolon in Clostridium difficile colitis. PMID- 2217024 TI - Silent nocardia cerebral abscesses in treated dermatomyositis. PMID- 2217025 TI - Discharge from osteomyelitis sinus with heparin therapy. PMID- 2217026 TI - Metyrapone-induced alopecia. PMID- 2217027 TI - Neurothanatology--clinical significance of cerebrally induced cardiac changes. PMID- 2217029 TI - An audit of the usage of operating theatre time in a peripheral teaching surgical unit. AB - A recent report by the National Audit Office found that only 50% to 60% of weekday operating time was being used. This report was examined by the Committee of Public Accounts and much of the blame for underutilization of operating theatres was attributed to poor working practices among surgeons. We investigated theatre utilization in our hospital and found underutilization on the same scale as the National Audit Office. Twenty-five per cent of theatre sessions were not allocated for use, 23% of general surgical lists were cancelled and, of the lists which did take place, a further 23% of theatre time was not utilized. The single largest cause of underutilization was understaffing. To increase theatre utilization higher levels of staffing and expenditure are needed rather than changes in the working practices of surgeons. PMID- 2217031 TI - Medical training in the European Community. AB - The free movement of doctors within the European Community demands harmonization of standards of medical practice and carries major implications of an undergraduate and postgraduate educational kind. These have begun to be addressed by the first three Medical Directives and also by a series of reports produced by the Advisory Committee on Medical Training to the European Community. This Committee was established in 1975 in order to provide informed agreed advice to the Commission. Many tasks remain to be tackled. A system of mutual inspection of the examination processes and standards in Member States should be established. Control must be exercised over the numbers of doctors produced since educational resources, including numbers of patients available for study, are limited. Thus, excellent standards of medical practice can only be developed and maintained if the primacy of clinical skills derived from the study of patients is recognized as essential in this respect. In some Member States at the present time there are many unemployed and therefore presumably deskilled doctors. PMID- 2217030 TI - Lornoxicam, indomethacin and placebo: comparison of effects on faecal blood loss and upper gastrointestinal endoscopic appearances in healthy men. AB - Forty-five healthy men aged 21-34 years took part in a double-blind, parallel group, placebo-controlled study of the effects of 28 days' treatment with lornoxicam 4 mg twice daily or indomethacin 50 mg twice daily on faecal blood loss and the endoscopic appearances of gastric and duodenal mucosa. After an initial endoscopic examination, subjects received, intravenously, on day 0, autologous erythrocytes labelled with 51Cr. Complete daily faecal collections were then made from days 6-12, 20-26 and 34-40. The drug treatments or placebo were given from days 13-41. Faecal blood loss was calculated from 51Cr-specific activity of blood and faeces. Endoscopy was repeated 4-8 hours after the last dose of medication; mucosal appearance was graded on a 5-point scale. Lornoxicam caused no more adverse events than placebo; indomethacin caused more indigestion and central nervous system effects, and one subject in this group was withdrawn from the study. Median total blood losses during the pre-treatment and the second and fourth weeks of treatment were respectively 3.33, 3.95 and 5.71 ml for lornoxicam, 2.87, 7.04 and 7.75 ml for indomethacin, and 4.55, 3.64 and 4.13 ml for placebo. Differences between treatments were not statistically significant (P = 0.081 for second week of treatment, P = 0.383 for fourth week of treatment; Kruskal-Wallis test). The effect of chlortenoxicam on faecal blood loss in this study was thus intermediate between placebo and indomethacin, but within- and between-subject variability was such that the differences were not statistically significant. Endoscopic findings were normal in most subjects before and after all treatments, but indomethacin was associated with a slightly greater deterioration in endoscopic score and was the only treatment associated with Grade 3 appearance (in a single patient) in post-treatment endoscopy. PMID- 2217032 TI - Pulmonary infiltrates and fever induced by isoniazid. AB - An 88 year old woman with bacteriologically confirmed pulmonary tuberculosis was first treated with isoniazid, rifampicin and pyrazinamide. Two weeks later she developed pulmonary infiltrates with fever. A drug-induced reaction was suspected but the reaction recurred three times until isoniazid was identified as the cause. The reaction became worse each time, finally being nearly fatal. PMID- 2217028 TI - Haematology. PMID- 2217033 TI - Fibroadenosis of the breast does not require excision biopsy. PMID- 2217034 TI - Specialized gastrointestinal units for the management of upper gastrointestinal haemorrhage. AB - In 1986, 292 patients were admitted to a joint medical-surgical gastrointestinal unit with upper gastrointestinal haemorrhage. Fourteen patients died (4.8%) a mortality considerably lower than recorded in most series. The low mortality may result from the use of a specialized gastrointestinal unit to which all patients with upper gastrointestinal haemorrhage are admitted and managed with strict protocols for resuscitation, transfusion and surgery. PMID- 2217035 TI - Haemorrhagic pancreatitis--a cause of death in severe potassium permanganate poisoning. AB - Severe potassium permanganate poisoning (more than 10 g of potassium permanganate) is invariably associated with massive systemic upset and death. Multiple organ damage has been recognized as an inevitable consequence of such an overdose, although pancreatitis has not been previously reported. Death due to cardiovascular collapse and profound hypotension is a common end point in those who reach hospital, but the pathogenesis is uncertain. We report a case of haemorrhagic pancreatitis following an overdose of potassium permanganate and suggest that this complication may be an unrecognized factor contributing to the extremely high mortality rate associated with this condition. PMID- 2217036 TI - Body packing--a case report and review of the literature. AB - Drug smuggling by internal bodily concealment is a growing international problem. The management of a patient who swallowed packages containing heroin is described. The medical management, indications for surgery and the ethical dilemmas of treating patients with drugs concealed within the gastrointestinal tract are discussed. PMID- 2217037 TI - Early diagnosis of Graves' optic neuropathy using visual evoked responses. AB - A 27 year old woman with Graves' disease developed progressive ophthalmopathy and was noted to have abnormal visual evoked responses (VER). She was treated with high dose prednisone with clinical improvement and return of the visual evoked responses to normal. On withdrawal of steroids symptoms recurred and VER again were abnormal. Orbital irradiation was given with improvement in the ophthalmopathy and VER again normalized. To our knowledge this report represents the first demonstration of improvement in VER with treatment in Graves' optic neuropathy. PMID- 2217038 TI - Multiple sclerosis associated with water intoxication. AB - We present a case of well documented multiple sclerosis which presented with the syndrome of inappropriate antidiuretic hormone secretion, following an exacerbation of the disease. This is a poorly documented association. PMID- 2217039 TI - Chronic bronchial suppuration and antineutrophil cytoplasmic antibody (ANCA) positive systemic vasculitis. AB - Two patients with long-standing chronic bronchial suppuration developed antineutrophil cytoplasmic antibody (ANCA) positive Wegener's granulomatosis and microscopic polyarteritis respectively. There is published evidence of an association between previous suppurative respiratory disease and Wegener's granulomatosis. We believe that our cases provide further evidence that chronic lung infection may play an aetiological role in the development of ANCA-positive systemic necrotizing vasculitis in some individuals. PMID- 2217040 TI - Diagnostic aspiration of an iatrogenic hydrothorax following subclavian catheterization. AB - Central venous catheterization is not without hazard. Inadvertent placement in the pleural space can occur without the development of a pneumothorax and pressure measurements may appear misleadingly normal. This case report illustrates an effective method of diagnosing and draining an iatrogenic hydrothorax which resulted in this way. PMID- 2217041 TI - Spontaneous rheumatoid fistula of the elbow joint. AB - A case of rheumatoid arthritis, whose presenting problem was a non-infective fistula of the elbow joint, is described. Penicillamine therapy was ineffective, but synovectomy led to healing. PMID- 2217042 TI - Subcutaneous sarcoidosis mimicking carcinoma of the breast. AB - A 65 year old woman presented with bilateral breast lumps. Clinical examination suggested a diagnosis of mammary carcinoma, but a histological diagnosis of sarcoidosis was made. Subsequent investigations revealed evidence of pulmonary sarcoidosis. PMID- 2217043 TI - An unusual omental hernia. AB - A unique case of a type of omental hernia is presented, which caused small bowel obstruction. The hernia is described and possible aetiological factors discussed. PMID- 2217044 TI - Large bowel obstruction due to an impacted barolith--a delayed complication of a barium study. AB - Complications of barium sulphate studies abound in the literature but there are very few recorded instances of large bowel obstruction due to inspissated barium and faeces forming a 'barolith'. A patient who suffered this complication is reported. PMID- 2217045 TI - Iron deficiency in autoimmune chronic gastritis. PMID- 2217046 TI - Retinal infarcts and haemorrhages due to scurvy. PMID- 2217047 TI - Hyperparathyroidism and cerebral haemorrhage. PMID- 2217048 TI - Partially reversible nerve deafness due to vincristine. PMID- 2217050 TI - Academic schizophrenia. PMID- 2217049 TI - Chemical de-bulking of desmoid tumours. PMID- 2217052 TI - Cultural diversity: a resource in planning and implementing nursing care. AB - America's cultural diversity challenges the ability of nurses to respond with sensitivity to client needs. Enhancement of the client's health practices is contingent on the nurse's ability to use the individual's culturally based beliefs and values as an integral component in the design of nursing interventions. Nurse and client engage in a truly collaborative planning and implementation of care only after there is mutual understanding of the special meaning of beliefs and values from which health behaviors are derived. Educational preparation with experience in applying cultural knowledge is essential to the development of sensitive nursing practice. Integrating such information and experiences into baccalaureate nursing curricula through a sociocultural project will enhance student awareness of client values and beliefs and their potential nursing implications. Strategies exist for helping students recognize, accept, and use these features in planning and implementing nursing care. PMID- 2217051 TI - The dependency at discharge instrument as a measure of resource use in home care. AB - The dependency at discharge instrument, developed to evaluate the needs for care of hospitalized patients on the day of discharge, was tested for its usefulness in measuring resource consumption in home health care. The instrument evaluates dependency in relation to bathing/hygiene, activity, technical procedures, and monitoring signs and symptoms. The sample used in this study consisted of 150 subjects admitted to one of three types of home health care agencies. Interrater reliability and internal consistency of the instrument were high. Factor analysis produced results similar to those of the developers for three of the four scale items. The item concerning need for assistance with procedures had a much lower loading, indicating that it had little in common with the other items. Criterion based validity was measured by testing the instrument's ability to predict the number of registered nurse and home health aide visits, and length of enrollment. Findings indicated that the instrument had a modest level of criterion-based validity in predicting the use of registered nurse and home health aide services for the hospital-affiliated agency, but was relatively ineffective for public health and for-profit agencies. PMID- 2217053 TI - Core curriculum for master's-level community health nursing education: a comparison of the views of leaders in service and education. AB - This study identified core components of the curriculum for master's-level community health nurses (CHNs) and assessed whether leaders in service agreed with leaders in education on the importance of these components. Through a mailed survey, 588 leaders in CHN service and education identified the following as the most important to include in the core CHN curriculum: a practicum experience; epidemiology; community health assessment and diagnosis; administration and management, including public health administration, management theory, program planning and evaluation, financial management and budgeting, and quality assurance; research methods and biostatistics; health promotion and disease prevention; intervention at the aggregate level; and leadership theory. These leaders also indicated that skills in both administration and direct care are essential for CHN practice. While there was remarkable agreement between service and education leaders in many areas, notable disagreements were seen in the importance accorded administrative skills. Service leaders rated these skills much more highly than did leaders in education. PMID- 2217054 TI - External family structure and cohesion: nursing perspectives. AB - The family is recognized as a basic unit in the delivery of many nursing services. The dimensions of its structure and cohesion may be important in the development of many family problems and should be assessed in planning nursing interventions in family-based care. This paper examines the impact of external family structure on the cohesion of a family encountered during a community-based student clinical experience in communications. External structural factors were considered in planning nursing interventions to alleviate stress-related symptoms and conflicts, and to enhance cohesion in clinical work with this family. PMID- 2217056 TI - Public health nurses and family planning. AB - Unintended pregnancy is a health problem that is particularly important in the practice of public health nurses (PHNs). Data from 844 PHNs showed that they were likely to practice in settings that incorporate family planning services and were knowledgeable about specific family planning methods. They favored family planning services and an expanded supportive government role in both family planning and abortion. Since PHNs are an important resource for the community activism required to build the consensus needed to expand these services, a multiple-regression analysis was performed to determine predictors of activism. Political participation was the major predictor for activism on both family planning and abortion. PMID- 2217055 TI - Symbiotic and synergistic community-based volunteer home visiting program for postpartum families. AB - Community health nurses who focus on the needs of the community as client, and not simply individual and family services, are aware of the demand for increased services. This demand, however, is usually coupled with the absence of resources to deliver the needed services. Therefore, leaders in community agencies must consider attracting nurses as volunteers to augment resources. Volunteer service can be highly synergistic when a symbiotic relationship exists between the agency and the volunteer. A one-year volunteer home visiting program was developed to provide services to families with new infants at one U.S. Army installation in the western United States. We assume the program methodology would be successful in civilian communities as well as other client populations. PMID- 2217057 TI - Public health nurse salaries: associations with nurse, agency, and community characteristics. AB - This study applied an economic framework to the analysis of public health nurse (PHN) salaries, assessing their relationships to nurse qualifications, agency resources, community economic base, and area competition for the nurse supply. Data were obtained through interviews with 125 Ohio health departments and from various state and local reports. Associations between salaries and explanatory variables were analyzed through correlations and stepwise regression models. The PHN salaries were significantly lower and more compressed than salaries for nurses in area hospitals. Agency and community characteristics were more important than nurse education and experience in explaining salary variations. Maximum PHN salary attainable was significantly related to level of health department funding and community unemployment rate. Health departments in rural locations paid lower salaries at both minimum and maximum levels. Evidence suggested the presence of entry-level wage competition by health departments with both area hospitals and other community nursing agencies. Each 1% increase in minimum hospital nurse salaries was linked to a 0.66% increase in PHN salaries. Findings support the need to improve competitive positions of health departments as nurse shortages intensify. PMID- 2217059 TI - Computers demystified. PMID- 2217058 TI - Malignant melanoma of the foot. PMID- 2217060 TI - Why GPs need to use the computer. PMID- 2217061 TI - The consulting room computer--friend or foe? PMID- 2217063 TI - Computer use and the new contract. PMID- 2217062 TI - Computers in the practice. Facilitating clinical care. PMID- 2217064 TI - Choosing a computer system. PMID- 2217065 TI - The doctor's bag. PMID- 2217066 TI - A request for a strong analgesic. PMID- 2217068 TI - Immunisation by health visitors. PMID- 2217067 TI - The internal examination. PMID- 2217069 TI - Recovery from a heart attack. PMID- 2217070 TI - Anaemias. PMID- 2217071 TI - Abnormal white blood cell count. PMID- 2217072 TI - Sickle cell disease in the UK. PMID- 2217073 TI - Polycythaemia. PMID- 2217075 TI - Abstracts of the XX Annual Nordic Meeting on Biological Alcohol Research. 13. 15.5.1990, Espoo, Finland. PMID- 2217074 TI - Bone marrow transplantation. PMID- 2217076 TI - Immunocytochemical localization of peroxisomal beta-oxidation enzymes in human fetal liver. AB - In the majority of congenital peroxisomal disorders, beta-oxidation of very long chain fatty acids is deficient. We have investigated the appearance and localization of the three peroxisomal beta-oxidation enzymes in normal fetal liver (fertilization age between 5 and 18 weeks) with protein A-gold immunocytochemistry and silver enhancement for light microscopic visualization. With specificity-tested polyclonal antibodies, acyl-CoA-oxidase, bifunctional enzyme, and 3-oxoacyl-CoA thiolase were localized in the peroxisomes of the parenchymal cells, which appear as brown or black granules. In the youngest specimen, no immunopositive reaction was obtained. A weak reaction with anti thiolase was obtained at the age of 6-7 weeks. At a fertilization age of 8 weeks, peroxisomes could be distinctly visualized after immunostaining for all three enzymes. From a staining series with anti-thiolase on simultaneously treated slides, it appears that the amount of antigen per peroxisome and the organelle size increase between the seventh and eighteenth weeks. These data should enable a more specific diagnosis in fetal liver biopsies from pregnancies at risk and after termination of pregnancy. PMID- 2217077 TI - Genetic amniocentesis: 505 cases performed before the sixteenth week of gestation. AB - Between May 1987 and November 1988, 505 early amniocentesis within the 15th week of gestation were performed at the First Department of Obstetrics and Gynaecology, 'L. Mangiagalli' of the University of Milan and at the Department of Obstetrics and Gynaecology of 'Gaslini' hospital in Genoa. A total number of ten abnormal fetal karyotypes were diagnosed. In addition, one case of pseudomosaicism (not confirmed on fetal blood) and one case of osteogenesis imperfecta type II (observed at ultrasound examination) were also detected. Eleven pregnancies were therefore terminated because of an abnormal fetus. Out of 494 pregnancies (excluding terminated pregnancies) there were 16 fetal losses within the 28th week; ten of these occurred in the 2 weeks following the procedure. There were 475 live-births, of which 447 were term deliveries and the other 28 deliveries occurred before the 37th week of gestation. PMID- 2217078 TI - Simultaneous placentacentesis and amniocentesis for prenatal karyotyping: report on 250 cases. AB - The efficacy and risks of simultaneous transabdominal chorionic villus biopsy (placentacentesis) and amniocentesis in the second and third trimesters were evaluated in 250 singleton pregnancies. The major indications were advanced maternal age (36.0 per cent), abnormal ultrasound findings (23.2 per cent), and low maternal AFP value (17.6 per cent). Nine abnormal karyotypes were found in placental tissue (3.6 per cent). The karyotypes of placental and amniotic cells were different in three cases, including two cases of false-positive mosaicism (0.8 per cent) and one case of a false-negative result (0.4 per cent) obtained by placental karyotyping. The problem of discrepant karyotypes in embryonic and extra-embryonic tissue does not seem to be restricted to the first trimester. The post-procedure fetal loss rate was estimated as approximately 1.8 per cent. We conclude that the procedure presented here combines the advantages of rapid karyotyping (placentacentesis) and high diagnostic reliability (amniocentesis). It does not seem to be necessary to restrict its use to late presentations and suspicious ultrasound findings. PMID- 2217080 TI - Spontaneous resolution of cystic hygroma in a 46,XX normal female. AB - We report a case of nuchal cystic hygroma with spontaneous resolution detected by ultrasound examination at 13 weeks' gestation. Fetal karyotype and amniotic fluid alpha-fetoprotein levels were normal. Extreme caution in evaluating this situation is stressed. PMID- 2217079 TI - Megacystis-microcolon-intestinal hypoperistalsis syndrome in two male siblings. AB - Two male sibs with severe congenital megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) are presented. Both had enlarged bladder and hydronephrosis due to reduced bladder emptying, decreased bowel motility, and malrotation of the colon. Repeated careful ultrasound examination of the urinary tract in the second sib failed to show significant bladder enlargement prior to 25 weeks' gestation, which has been considered to be a reliable prenatal diagnostic sign for MMIHS. Slight bilateral enlargement of the renal pelves was noted at 21 weeks' gestation, and this may represent the earliest prenatally detectable observation in this disease. Although more females than males with this condition have been reported, our cases provide support for an autosomal recessive mode of inheritance with a similar recurrence risk for both sexes. PMID- 2217081 TI - Delta F508 gene deletion and prenatal diagnosis of cystic fibrosis in Italian and Spanish families. PMID- 2217082 TI - Fermentation of pearl millet flour with yeasts and lactobacilli: in vitro digestibility and utilisation of fermented flour for weaning mixtures. AB - Single as well as mixed culture fermentation by yeasts (S. diastaticus; S. cerevistiae) and lactobacilli (L. brevis; L. fermentum) at 30 degrees C for 72 h improved the starch and protein digestibility (in vitro) of pearl millet flour significantly. The flour fermented by Saccharomyces diastaticus, a starch hydrolysing yeast, had the highest starch digestibility whereas fermentation by Saccharomyces cerevisiae enhanced the in vitro protein digestibility of the flour significantly. Weaning mixtures prepared from the fermented flour were also found to be organoleptically acceptable. PMID- 2217083 TI - Biological evaluation of pearl millet protein: effect of different treatments and storage. AB - Whole grain flour of one variety (HC-4) of pearl millet (Pennisetum americanum L. Leeke) after giving different treatments (defatting, butylated hydroxyanisole, ascorbic acid and thermal) was stored in earthen pots at prevailing room temperature (28-34 degrees C) and relative humidity (70-80%) for 30 days. The flour samples were evaluated for protein quality using rats. Storage of flour for 30 days markedly reduced the protein quality. The values of protein efficiency ratio, true digestibility, biological value, net protein retention and net protein utilisation were significantly (P less than 0.05) higher in fresh and treated flour than untreated flour. Among treated flours, defatted flour showed best growth followed by butylated hydroxyanisole, thermal and ascorbic acid treated flour. PMID- 2217084 TI - Irradiation and germination effects on phytate, protein and amino acids of soybean. AB - Influence of irradiation (0.05-0.20 kGy) and germination (24-120 hours) in distilled and tap water on phytate, protein and amino acids of soybean, was studied. Phytate values significantly decreased with increasing germination period and irradiation dose (P less than 0.01). Irradiation independently decreased the original phytate (212.0 mg/100 g) to a range value of 205.0-190.0 mg/100 g depending upon dose level. Germination of unirradiated seeds for 120 hours in distilled and tap water lowered the phytate to 55.0 and 94.9 mg/100 g (74.1 and 55.2% reduction) respectively. Maximum destruction of phytate to levels of 20.5 and 50.9 mg/100 g (90.3 and 76.0% reduction) occurred during germination of 0.20 kGy samples for 120 hours in distilled and tap water respectively. Total protein content significantly increased during germination (P less than 0.05) and the increase was more in tap than distilled water. Germination for 120 hours of untreated seeds in tap water increased the essential and decreased non-essential amino acids while in the 0.10 kGy sample, increases in both cases were observed. PMID- 2217085 TI - Seed protein yield from some Crotalaria spp and in vitro nutritional quality of that from C. juncea. AB - Seed Protein Concentrates (SPC) of 6 species of Crotalaria were extracted and the extractabilities of SPC, total N and protein N determined. SPC of high yielding species (C. Juncea) was analyzed for the contents of amino acids, ash, phosphorus, sugar, starch, fibre and calories, as well as for in vitro digestibility. Results indicate the promising potential of C. juncea for SPC yield. PMID- 2217087 TI - [Bronchial carcinoma--a challenge for pneumology]. PMID- 2217086 TI - Effect of processing on the nutritive value of Canavalia Jackbeans (Canavalia ensiformis L). AB - A comparative study of roasting, cooking with and without calcium hydroxide and extrusion cooking on the protein quality of Canavalia was conducted. The results suggested both extrusion and pressure cooking with lime to be equally effective in improving the protein quality of Canavalia and superior to pressure cooking alone and roasting, the latter effective possibly in destroying the antiphysiological factors in Canavalia but possibly also damaging its protein quality. The individual effects of roasting, cooking with different levels of calcium hydroxide, and with water under pressure at different times on the protein quality of Canavalia were also studied. These indicated a beneficial effect of calcium hydroxide added at a level of 0.45% by weight of seed, for 30 minutes under pressure. Cooking in water under pressure for 30 minutes with and without lime added was slightly better than cooking for longer periods of time. Roasting was also effective in improving the quality of Canavalia particularly when the T was adjusted at 170 degrees C, and roasting conducted for 15 minutes. A significant improvement in the protein quality of processed Canavalia was obtained by methionine supplementation. PMID- 2217088 TI - [Early diagnosis of bronchial carcinoma]. PMID- 2217090 TI - [Lung function diagnosis using multi-frequency oscillometry with reference to lung volume]. AB - The ranking of various oscillometry parameters was to be tested in patients with a broad spectrum of disturbances of pulmonary function, objectified by body plethysmographic and technical oesophageal pressure measurement of the respiratory resistance, lung volumes and lung elasticity. For this purpose the oscillatory resistance Rfo and the phase angle phi were measured at 8, 12 and 16Hz and phi was measured as it changed, depending on the lung volume V. It was found that enhanced respiratory resistance values are satisfactorily represented by Rfo for the purposes of preliminary and basic diagnostics. Besides, enhanced Rfo values are markedly dependent on the frequency, phi being shifted to negative values. Difference between Rfo values at 8 and 16 Hz (delta R8-16) less than 0.7 hPa/l/s phi greater than or equal to -10 degrees can be considered as being still normal with the employed measuring principle and are a valuable supplement for assessing the degree of obstruction. The difference between phi in the medium respiratory position and at 90 or 100% total capacity (delta phi) is less than 5 degrees during slow inspiration in 80% of the patients suffering from emphysema. In 80% of the persons with healthy lungs and those suffering from fibrosis there is an inspiratory negativation of phi (delta phi greater than 5 degrees) so that the phi-V relationship appear suitable for distinguishing patients with restricted vital capacity in respect of emphysema and fibrosis. Patients suffering fron fibrosis differ from healthy subjects by slightly more negative phi values. The borderline values for delta R8-16, phi and delta phi were confirmed in two further series of examinations on children and adolescents. PMID- 2217089 TI - [Unilateral lung transplantation--a new perspective in the treatment of pulmonary fibrosis]. AB - In patients with pulmonary fibrosis and progressive respiratory failure despite conservative treatment, unilateral lung transplantation offers a new therapeutic alternative. At the Medical School in Hannover, five patients--the first to be thus treated in Central Europe--with terminal pulmonary fibrosis of the lung have so far been successfully treated with unilateral lung transplantation. All five patients are still alive, and all experienced a marked improvement in their pulmonary function parameters, such that they have been enabled to lead a normal life again. PMID- 2217091 TI - [Prognosis in cor pulmonale: predictive value of two-dimensional echocardiography]. AB - Cor pulmonale is a common complication and frequent cause of death in COLD. No published records are as yet available on the prognostic ranking of two dimensional echo-cardiography in this group of patients. In 79 of 85 (93%) consecutively echocardiographically examined COLD patients it was possible to effect apical imaging of the four-chamber view to assess the size of the right ventricle, as well as a subcostal imaging to analyse the respiratory performance of the vena cava inferior (vci). Among the exclusion criteria of this prospective series were a diseased condition of the left heart or other associated cardiac diseases. The patients were classified into two risk groups (RG 0 and RG 1) depending upon whether they had a normal-sized right ventricle or a complete inspiratory collapse of the vci, or not. In RG 1 the pO2 values were lower (56.8 +/- 9.2 vs 66.0 +/- 8.8 mmHg, p less than 0.0005) whereas the values for the respiratory passage resistance were higher (8.01 +/- 3.92 vs 6.22 +/- 2.87 cm H2O/l/s; p less than 0.025) than with RG 0, the values for the intrathoracic gas volume not being significantly different from each other. Fatal cardiopulmonary results were covered over a period of 2-48 months (median 24 months) to perform life table analyses according to Breslow and Mantel. Patients with an enlarged right ventricle or incomplete respiratory collapse of the vci have a lower survival rate (43.7% respectively 61.9%) than patients with a normal-size right ventricle or complete respiratory collapse of the vci (90.5% respectively 88%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2217092 TI - [Determination of theophylline serum level: comparison between a rapid test (enzyme-immuno-chromatography) and conventional fluorescence polarization immunoassay]. AB - To evaluate the reliability and accuracy of a rapidly performed enzyme immunochromatography method for measuring the serum concentration of theophylline, we compared it with a conventional technique (fluorescence polarisation immunoassay). We investigated 103 venous blood samples from children and adolescents with bronchial asthma, medicated with sustained-release theophylline preparations. There was a highly significant correlation of the measured values; with a few exceptions, the individual values scattered only narrowly around the regression line. Based on this close correlation, the investigated enzyme immunochromatography test can be recommended for rapid theophylline serum level determinations in clinical practice. PMID- 2217093 TI - [Sicca syndrome in sarcoidosis--an overlap syndrome?]. AB - This is a case report on a 66-year old woman who suffered from chronic polyarthritis for 15 years and developed a sicca syndrome pattern for 2 years. 2 years later epithelioid cell granulomas were found from a submandibular lymph node as well as from a suspicious area at the epiglottis and the mucosa of the upper lip. Moreover, there was a chronic keratoconjunctivitis and discrete lung involvement. The sarcoidosis on the lip and at the epiglottis disappeared, and lung involvement and conjunctivitis improved under corticosteroid therapy. In spite of above therapy, the sicca syndrome pattern and the rheumatic complaints (osteoporosis) persisted. PMID- 2217094 TI - [Pneumologie 44(1990), 74-77, G. Pothoff et al. Difficulties in the diagnosis of an AIDS-associated intrapulmonary Kaposi sarcoma]. PMID- 2217095 TI - [Drug safety, characteristic of dosed aerosols]. PMID- 2217096 TI - [The use of argon laser coagulation in the combination treatment of patients with tuberculous chorioretinitis]. AB - The outcomes of argon laser coagulation (ALC) of active tuberculous chorioretinal foci (mainly of exudative and hemorrhagic nature, macular and paramacular localization) in 26 patients are illustrated. The coagulation was performed concurrently with a combined general and local antituberculosis therapy (with 48 patients as controls). The developed direct ALC technique was used together with antibacterial therapy of the total surface of the inflammation focus itself. The examination findings prove that the effectiveness of the above technique is high, since the disappearance of the clinical signs of the inflammatory activity is achieved in a relatively short time (45 days); acute conditions and relapses are prevented; complications are excluded; and an evident economic effect is produced (the shorter period of hospitalization, less duration of the main therapeutic regimen and lower frequency of relapses). PMID- 2217097 TI - [Tuberculosis among socially predisposed groups of the population]. AB - Low incidence rates of tuberculosis are directly related to social factors, including higher morbidity among such groups as migrants, vagabonds, ex-convicts and alcohol abusers. In view of that it seems necessary to solve a problem of organizing tuberculosis-oriented treatment-and-labor preventoria to render health care to the vagabonds and other patients refusing medical intervention. Since presently there exists a wide diversity of tuberculosis morbidity rates among different community groups, tuberculosis control tactics should be based on the awareness of the associated risk factors, the existing level of epidemiological data and social and economic situation in a certain region. PMID- 2217098 TI - [The interrelation of bovine and human tuberculosis]. AB - For the last 5 years, the examination of the farms in the Ukrainian SSR revealed the following distribution of Mycobacterium cultures isolated from cattle: M. bovis, 50.5%, M. hominis, 0.4%; M. avium, 1.8%; and atypical bacilli, 47.3%. In 31% of the farms considered to be safe enough in relation to tuberculosis, tuberculin-sensitive cattle was identified, thus totalling 47.3% of these farms where as many as 15 types of atypical Mycobacteria were shown to cause its sensitization. Photochromogenic Myco. cultures were not isolated either from the cattle or from the environmental objects. Single cases of tuberculous cattle infected by the human hosts were found as a consequence of the violation of the rules adopted in the farms to prevent this disease. Bovine tuberculosis-infected people were not detected. PMID- 2217099 TI - [Differential diagnosis of tuberculosis of the intrathoracic lymph nodes in children and adolescents]. AB - Case histories and clinico-roentgenologic symptoms of 103 children with intrathoracic lymphatic tuberculosis and 66 with non specific intrathoracic adenopathies were analysed. As a result, considerable differences were revealed both in the natural history of intrathoracic adenopathies of tuberculous and nonspecific etiology and in the clinical symptoms and X-ray picture, making it possible to ascertain a nosologic diagnosis of the disease. A diagnosis-rating table for the most common diseases with underlying hyperplasia of the intrathoracic lymph nodes has been developed. PMID- 2217100 TI - [An experimental study of the chemotherapeutic efficacy of flurenizid, a new antitubercular pharmaceutical]. AB - The efficacy of a chemotherapeutic effect of flurenizid, a new antituberculous drug, was experimentally demonstrated. Flurenizid is an aromatic heterocyclic derivative. As estimated on the models of hematogenic disseminated and destructive pulmonary tuberculosis, a chemotherapeutic dose of the drug was 20 and 50 mg per kg body weight of an animal. Phagocytotic stimulation and fibrillogenetic intensification represent one of the mechanisms of its action. The most pronounced efficacy of flurenizid was noted when it was combined with isoniazid. PMID- 2217101 TI - [Hormonal shifts in adolescents in the initial period of infection with tuberculosis]. AB - In 78 adolescents aged 13-17 years, the functions of the pituitary body, adrenal and thyroid glands and pancreas were examined by means of radioimmunoassay. The controls were represented by 31 subjects with non-infected tuberculosis; in 47 adolescents, tuberculin test was seen to turn positive. The initial period of the tuberculosis infection in adolescents is marked by the following changes: inhibited pituitary function (other than adrenocorticotropic hormone); higher adrenal activity, elevated cortisol levels, altered (predominantly depressed) thyroidal function; and increased pancreas functional activity. The above changes indicate the inhibition of human defense forces and its comparatively high energy consumption. The presence of deviations in the physical development of adolescents, most frequently leading to an excessive weight, and pronounced tuberculin sensitivity aggravate the disturbance of the hormone equilibrium. PMID- 2217102 TI - [The results of antibacterial therapy combined with prodigiozan in children with tuberculosis]. AB - The paper presents the findings of a clinico-roentgenologic and immunologic follow-up of 100 children aged 3-14 years. The efficacy of the antibacterial treatment of children with different forms of intrathoracic tuberculosis supplemented by prodigiosan as well as that of prodigiosan alone were analysed by means of clinical, X-ray, laboratory and immunologic methods. By increasing the body reactivity, prodigiosan can promote higher rates of resolution of pathologic changes in the lungs. The data of this study permit one to recommend prodigiosan as an effective non-specific impact method in the combined treatment of tuberculosis in children. PMID- 2217103 TI - [The efficacy of sanatorium treatment of adolescents with destructive tuberculosis of the lungs]. AB - Compared to the urban population, tuberculosis morbidity among adolescents living in the rural areas means a greater number of serious cases prone to decomposition and dissemination processes as a consequence of their late detection. Sanatorium and health resort treatment of adolescents with destructive pulmonary tuberculosis appears to be highly effective in the institutions situated along the southern shore of the Crimea. PMID- 2217105 TI - [Characteristics of the phagocytic reaction of the neutrophils in healthy children and children with acute bronchitis and varying sensitivity to tuberculin]. AB - The feature of blood neutrophils to phagocyte BCG Mycobacterium and Staphylococcus in healthy children and those with acute bronchitis having both positive and negative tuberculin tests was analysed. Healthy children with an altered tuberculin response demonstrate an intensified phagocytic Myco. reaction and a relative inhibition of staphylococcal phagocytosis. In case of acute bronchitis, there is no increase in the overall absorbing capacity of neutrophils, typical of the tuberculin-negative children, and consequently, the detected feature of the phagocytosis is eliminated. The absence of variations in the total phagocytic response of the affected children is considered as a decrease of their adaptation potential. It is presumed that such an immunological status can predetermine the course of respiratory diseases and be the cause of tuberculous infection reactivation with intercurrent diseases. PMID- 2217104 TI - [The application of a temporary occlusion of the bronchi to restore their hermetic state following resection of the lung]. AB - A temporary occlusion of the bronchi to restore their tightness in the postoperative period was carried out in 106 persons aged 18-65 years. The indications of occlusion were determined on the basis of the air outflow volume along the pleural drainage, subcutaneous emphysema presence and residual pleural cavity dimensions. In 90 patients, a temporary bronchial occlusion lasting for 2 4 days was performed 1-2 days after the operation. In 16 other patients, it was done on postoperative days 10-15 (with an occlusion period of 15-30 days and the obturator being replaced every 5-7 days). Due to the occlusion, the desired effect was achieved in 77 patients by completely restoring lung suture tightness and eliminating residual pleural cavity. A partial effect was produced in 18 subjects which manifested as a 2-3-fold reduction in the residual pleural cavity dimensions as compared to the initial one. In 11 persons, the occlusion happened to be ineffective. PMID- 2217106 TI - [Thrombohemorrhagic and acute circulatory complications of the surgical treatment of tuberculosis]. AB - The results of a number of studies on the hemostasis system in pulmonary tuberculosis patients are presented, and the analysis of pathophysiological processes of great importance in the development of intravascular hemocoagulation is made. It is clearly proved that an indispensable condition for the development of a complex of measures to increase the effectiveness of preventive treatment of thrombohemorrhagic and acute dyscirculatory complications after surgical management of tuberculosis patients is to define concrete biochemical mechanisms fundamental for intravascular hemocoagulation when certain hemostatic abnormalities occur during operation. PMID- 2217107 TI - [The state of the liver in rabbits during combination chemotherapy of experimental disseminated tuberculosis]. AB - Functional and morphologic changes in the liver condition of experimental rabbits were studied in the process of the disseminated tuberculosis development and treatment. Medication of the animals was started 2 weeks after the infection at the peak of the process and continued for 60 days. In Group 1 of the rabbits, isoniazid and rifampicin were administered enterally in combination with intramuscular streptomycin, and in Group 2, isoniazid and rifampicin were given intravenously plus intramuscular streptomycin. The doses of the antibacterial drugs were adequate, as compared to the clinical ones. It was shown that an intravenous administration of isoniazid and rifampicin supplemented by intramuscular streptomycin resulted in more pronounced normalization of processes in the liver morphologic and functional changes caused by tuberculosis than an enteral route of administration of the drugs. PMID- 2217108 TI - [The efficacy of 6 months' chemotherapy of newly diagnosed patients with pulmonary tuberculosis]. PMID- 2217109 TI - [Morphological manifestations of secondary immunodeficiency]. PMID- 2217110 TI - [Indirect pharmaco-angioscintigraphy of the kidneys in patients with cavernous renal tuberculosis]. AB - Radionuclide examination findings of the renal hemodynamics of 70 patients with cavernous tuberculosis of the kidney are presented. Before the indirect radionuclide pharmacoangiography, 58 of these patients received two groups of drugs having different impact on renal vessels. The indirect radionuclide pharmacoangiography method is atraumatic and highly informative, and allows one to evaluate a morphofunctional status of the renal vessel channel in patients with tuberculosis of the kidney for the purpose of treatment tactics assessment and complex therapy efficacy monitoring. The sensitivity and accuracy of the method are 81 and 86%, respectively. PMID- 2217111 TI - [Generalized tuberculosis today]. PMID- 2217112 TI - [The treatment of tuberculosis of the lungs complicated by bronchial pathology in elderly patients]. PMID- 2217113 TI - Growth, morphology and division of flagellates of the genus Trypanoplasma (Protozoa, Kinetoplastida) in vitro. AB - Nine strains of trypanoplasms were grown in axenic culture. Cultures of Trypanoplasma borreli Laveran and Mesnil, 1901 from fish hosts Blicca bjoerkna, Cyprinus carpio, Scardinius erythrophthalmus and Tinca tinca and of T. guerneyorum Minchin, 1909 from Esox lucius and Trypanoplasma spp. from the leech Piscicola geometra were maintained in biphasic blood-agar medium SNB-9 supplemented with vitamins and antibiotics. In culture, the flagellates transformed into smaller, elongated stages with a little-developed undulating membrane and into short flagella that were morphologically similar to stages in the leech vector. The cultures were passaged weekly at 17-20 degrees C, but they also grew at 4 degrees C. The flagellates divided by binary fission, which was initiated by the formation of two new anterior flagella. The original anterior flagellum of the mother individual was gradually apposed to the cell surface and became the recurrent flagellum of one of the daughter individuals. In the meantime, nuclear division took place, followed by transverse cleavage of the kinetoplast. The division was completed by longitudinal fission of the mother individual into two offspring. Multiple fission that resulted in rosettes, which then cleaved into several daughter cells, was also observed, as well as some dyskinetoplastic and other anomalous forms. In cultures isolated from tenches with high parasitaemia, non-dividing, long filiform stages were observed. Culture stages were not infective for susceptible fishes. PMID- 2217114 TI - Exocytosis of Toxoplasma gondii dense granules into the parasitophorous vacuole after host cell invasion. AB - Tachyzoites of Toxoplasma gondii have been shown to exocytose the contents of dense granules into the parasitophorous vacuole after host cell invasion. A monoclonal antibody specific for a 27-kDa protein was used to locate the dense granules by immunoelectron microscopy. The same antibody also reacted with the tubular network found in the parasitophorous vacuole, which confirmed that the dense granules were exocytosed by tachyzoites. PMID- 2217115 TI - Isolation of the pellicle of Toxoplasma gondii (Protozoa, Coccidia): characterization by electron microscopy and protein composition. AB - Two methods were compared for the isolation of the Toxoplasma gondii pellicle: centrifugation using a discontinuous sucrose gradient and affinity purification by microspheres activated with protein A. Electron microscopy showed that these two means of purification gave similar results, although better yields were obtained with the former than with the latter. Proteins of membrane fractions isolated using sucrose gradient were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Bands in the molecular-weight regions of 19, 22, 35, and 79 kDa appeared to be associated with the T. gondii pellicle. PMID- 2217116 TI - A new method for purification of Eimeria tenella merozoites. AB - A rapid and simple method for purifying second generation merozoites of Eimeria tenella was developed using a host tissue digestion fluid, containing 0.25% trypsin and 0.5% taurodeoxycholic acid, to liberate merozoites grown in chick embryos or from parasitized ceca. After filtration, the digestion procedure yielded 1.4 x 10(7) or 8.33 x 10(7) merozoites per embryo or cecum, respectively. These yields were nine-fold for embryos and three-fold for ceca in comparison to previous reports. Viability of the merozoites was normal as assessed by their ability to reinfect embryos and cell cultures. The new method has advantages in that large numbers of pure, viable merozoites can be obtained quickly and easily, and the procedures require minimal effort and supplies. PMID- 2217118 TI - Evidence for surface-coat localisation of a monoclonal antibody-isolated merozoite antigen of Babesia divergens. AB - The localisation of monoclonal antibody-derived merozoite antigens of Babesia divergens was examined using immunogold electron microscopy and immunoprecipitation of the monoclonal antibody with both biosynthetically and surface-labelled parasites. Immunogold labelling provided evidence that the antigens are components of the surface coat of the merozoite. Immunoprecipitation with biosynthetically labelled parasites showed the antigens to be of parasite origin, whereas surface labelling confirmed that the antigens form part of the surface coat. PMID- 2217117 TI - The effect of ascaridole on the in vitro development of Plasmodium falciparum. AB - Ascaridole is a terpene isolated from the plant Chenopodium ambrosioides (American wormseed); it is one of the few naturally occurring endoperoxidases. Artemisinin, which also belongs to this group, is a potent antimalarial. We therefore undertook a study to determine the effect of ascaridole, a known anthelmintic, on the in vitro development of Plasmodium falciparum. Ascaridole was found to be a potent inhibitor of plasmodial growth; after 3 days, development was arrested by a drug concentration of 0.05 microM, and at 0.1 microM no parasites were visible in the culture. At lower concentrations the effect was observed mainly at the trophozoite stage, whereas the ring stage was marginally affected. However, even at these lower concentrations, the ring culture could not continue normal development and ceased to grow at a later stage. The peroxide group is essential for the antimalarial activity of ascaridole, as judged from the fact that cineol, which bears an epoxide group instead of the peroxide group found in ascaridole, was totally inactive at identical concentrations. PMID- 2217119 TI - Characterization and purification of culture-derived soluble glycoproteins of Babesia canis. AB - The addition of [14C]-glucosamine to media of Babesia canis cultures causes the appearance of labeled glycoproteins in the culture supernatants. These radioactive soluble glycoproteins were separated according to their molecular weight by gel filtration and according to their (acidic) pI by preparative electrofocusing. The labeled fractions were then analyzed by SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). The results showed three series of glycoproteic antigens. The molecular weights for the three antigens determined by gel filtration and by SDS-PAGE were approximately 100, 40, and 12.5 kDa, and the preparative gel electrofocusing suggested that the antigens focus in the pH range of 3-5. PMID- 2217120 TI - Adherence and multiplication of Giardia intestinalis on human enterocyte-like differentiated cells in vitro. AB - This report describes a technique for studying the adherence and growth of Giardia intestinalis trophozoites (strains PARIS/86/LCF/1, PARIS/86/LCF/2 and PARIS/88/LCF/8) using the human colon carcinoma cell line Caco2. Giardia trophozoites were cultured with Caco2 cells in a modified HSP3 culture medium. The biochemical differentiation of Caco2 cells was established by an increase in sucrase isomaltase activities to values of 4.51 +/- 0.90 and 10.39 +/- 3.00 milliunits/mg protein for 8- and 12-day-old cultures, respectively. Giardia, adherence to 8- and 12-day-old Caco2 cells reached a value of greater than 75% after 60 and 30 min, respectively. Adherence diminished significantly at 24 degrees C and was almost undetectable at 4 degrees C. Depletion of divalent cations reduced the proportion of adherent trophozoites by up to 46%. Adherence was pH-independent between pH 6.0 and 7.6. Parasite growth increased when Caco2 cell monolayers were used instead of axenic cultures. This in vitro human cell model may contribute to the study of the mechanisms and factors involved in the host-parasite interaction. PMID- 2217122 TI - Species variation in mosquito flight-muscle damage resulting from a single filarial infection and its repercussions on a second infection. AB - Serial sections of females of two highly filaria-susceptible mosquitoes, Aedes togoi and Ae. aegypti, were examined by light microscopy. Following a single Brugia pahangi infection, the predominant reaction of flight muscles of Ae. aegypti was degeneration, whereas that in Ae. togoi was nuclear enlargement, a putative repair response. This also holds true following mechanical injury (Beckett 1990), suggesting an inherent species difference in flight-muscle response to injury. The filariae of a second B. pahangi infection, initiated after muscle damage had been established, usually avoided degenerate muscle fibres (which cannot support larval development) but entered similar proportions of normal fibres and those with enlarged nuclei. Filariae of a second infection, initiated whilst first-infection larvae were still within the muscle fibres, entered similar proportions of already-parasitized and non-parasitized fibres. The sole change in muscle fibres detectable by filarial larvae is therefore degeneration. PMID- 2217121 TI - Mechanisms of eosinophil accumulation around eggs of Schistosoma japonicum: role of two purified components, allergen and eosinophil chemotactic factor, from soluble egg antigens measured on sensitized guinea pig skin. AB - Mechanisms of eosinophil response induced by soluble egg antigen (SEA) in Schistosoma japonicum-infected guinea pig tissues were analyzed using two purified components of SEA: major allergenic components (JEAL) and a major eosinophil chemotactic component (ECF-SjE). Eosinophil response to the crude SEA of S. japonicum was detected at the injection site mainly at 2-8 h after the antigenic challenge; this response consisted of two different phases of eosinophil attraction. An early phase (2 h) was mediated by an immediate-type hypersensitivity reaction; JEAL played an important role in mediating this phase of eosinophil response. A late phase (8 h) was mediated by ECF-SjE. Therefore, this phase of eosinophil response was caused by direct eosinophilotactic activity of SEA. These two types of eosinophil response must be important processes in the formation of S. japonicum egg-associated eosinophilic granuloma. PMID- 2217123 TI - Loperamid, an efficacious drug against fish-pathogenic acanthocephalans. AB - A total of 20 drugs were tested for their efficacy in the treatment of infections involving the two major acanthocephalans infesting rainbow trout in European trout farms. In in vitro experiments, the antidiarrhoeic loperamid and the well known anthelminthic drug niclosamide showed the best efficacy. Worms treated with loperamid contracted the posterior end of their body, in which severe necrosis of the tegument caused the death of the worms. In in vivo experiments, loperamid was the most efficacious drug: 50 mg/kg given to rainbow trout on 3 consecutive days led to a complete cure. According to preliminary tolerance tests in water baths, the toxicity of this drug is low as compared with that of niclosamide, which is very toxic. Thus, loperamid can be recommended as the drug of choice for therapy of acanthocephalan infections in fish. PMID- 2217124 TI - Loperamid, an efficacious drug against the acanthocephalan Macracanthorhynchus hirudinaceus in pigs. PMID- 2217126 TI - A cyst-specific component of Pneumocystis carinii. PMID- 2217125 TI - Protective immunity to Leucocytozoon caulleryi in chickens by a killed vaccine. PMID- 2217127 TI - The nervous system of Diplostomum pseudospathaceum Niewiadomska, 1984 (Trematoda, Diplostomidae). IV. Nervous system and distribution of sensilla in the daughter sporocyst. PMID- 2217128 TI - The influence of Hymenolepis diminuta infection on IgA bound to mouse blood platelets. PMID- 2217129 TI - Praziquantel treatment of brain and muscle porcine Taenia solium cysticercosis. 2. Immunological and cytogenetic studies. PMID- 2217130 TI - Determination of reliable regions in protein sequence alignments. AB - Judging the significance of alignments is still a major problem in sequence comparison. We present a method to delineate reliable regions within an alignment. This differs from standard approaches in that it does not attempt to attribute one significance value to the alignment as a whole, but assesses alignment quality locally. An algorithm is provided that predicts which residue pairs in an alignment are likely to be correctly matched. The predictions are evaluated by comparison with alignments taken from tertiary structural superpositions. PMID- 2217131 TI - Sequence requirements for cytochromes P450IIA1 and P450IIA2 catalytic activity: evidence for both specific and non-specific substrate binding interactions through use of chimeric cDNAs and cDNA expression. AB - Cytochrome P450s IIA1 and IIA2, encoded by the CYP2A1 and CYP2A2 genes, display 88% amino acid sequence similarities. The dissimilarities of sequence between these two enzymes are primarily localized within four discrete regions of the polypeptides that are separated by regions of absolute sequence identity. IIA1 specifically hydroxylates the prototype substrate testosterone at the 7 alpha and 6 alpha position with a predominance of 7 alpha metabolite. IIA2, on the other hand, hydroxylates this steroid at eight positions on the molecule, with one of the most abundant metabolites being 15 alpha-hydroxytestosterone. To determine those amino acids responsible for the difference in testosterone hydroxylation specificities, chimeras were constructed between IIA1 and IIA2 cDNAs and expressed in cell culture using vaccinia-virus-mediated cDNA expression. Chimeras, in which the first 355 amino acids correspond to a single enzyme, maintain the specificity associated with that enzyme. Of six chimeras which have substitutions between amino acids 161 and 276, two are inactive and the remaining four give similar metabolite profiles, in which both 7 alpha and 15 alpha hydroxylation specificities have been lost. Two of these four chimeras are diametric apposites, suggesting that modification of either the N-terminal or central regions of the enzymes results in conformational changes that prevent the specific binding interactions responsible for the narrow regioselectivity associated with IIA1 and 15 alpha-hydroxytestosterone formation associated with IIA2. PMID- 2217132 TI - Alignment of protein sequences using secondary structure: a modified dynamic programming method. AB - A method for comparison of protein sequences based on their primary and secondary structure is described. Protein sequences are annotated with predicted secondary structures (using a modified Chou and Fasman method). Two lettered code sequences are generated (Xx, where X is the amino acid and x is its annotated secondary structure). Sequences are compared with a dynamic programming method (STRALIGN) that includes a similarity matrix for both the amino acids and secondary structures. The similarity value for each paired two-lettered code is a linear combination of similarity values for the paired amino acids and their annotated secondary structures. The method has been applied to eight globin proteins (28 pairs) for which the X-ray structure is known. For protein pairs with high primary sequence similarity (greater than 45%), STRALIGN alignment is identical to that obtained by a dynamic programming method using only primary sequence information. However, alignment of protein pairs with lower primary sequence similarity improves significantly with the addition of secondary structure annotation. Alignment of the pair with the least primary sequence similarity of 16% was improved from 0 to 37% 'correct' alignment using this method. In addition, STRALIGN was successfully applied to seven pairs of distantly related cytochrome c proteins, and three pairs of distantly related picornavirus proteins. PMID- 2217134 TI - Protein engineering of chymosin; modification of the optimum pH of enzyme catalysis. AB - The aspartic proteinase chymosin exhibits a local network of hydrogen bonds involving the active site aspartates and surrounding residues which may have an influence on the rate and optimal pH of substrate cleavage. We have introduced into chymosin B the following substitutions: Asp304 to Ala (D304A), Thr218 to Ala (T218A) and Gly244 to Asp (G244D, chymosin A), using oligonucleotide-directed mutagenesis. Kinetic analysis of these active mutants shows shifts in their pH optima to 4.4 D304A, 4.2 T218A and 4.0 G244D compared with 3.8 for chymosin B using a synthetic octapeptide substrate. The upward shift of the D304A and T218A may be due to the loss of hydrogen bond interactions indirectly affecting the catalytic aspartates 32 and 215. The G244D mutation which is in a flexible loop on the surface of the enzyme may alter the conformation of the specificity pockets on the prime side of the scissile bond. PMID- 2217133 TI - Influence of size and polarity of residue 31 in porcine pancreatic phospholipase A2 on catalytic properties. AB - Residue 31 of porcine pancreatic phospholipase A2 (PLA2) is located at the entrance to the active site. To study the role of residue 31 in PLA2, six mutant enzymes were produced by site-directed mutagenesis, replacing Leu by either Trp, Arg, Ala, Thr, Ser or Gly. Direct binding studies indicated a three to six times greater affinity of the Trp31 PLA2 for both monomeric and micellar substrate analogs, relative to the wild-type enzyme. The other five mutants possess an unchanged affinity for monomers of the product analog n-decylphosphocholine and for micelles of the diacyl substrate analog rac-1,2-dioctanoylamino-dideoxy glycero-3-phosphocholine. The affinities for micelles of the monoacyl product analog n-hexadecylphosphocholine were decreased 9-20 times for these five mutants. Kinetic studies with monomeric substrates showed that the mutants have Vmax values which range between 15 and 70% relative to the wild-type enzyme. The Vmax values for micelles of the zwitterionic substrate 1,2-dioctanoyl-sn-glycero 3-phosphocholine were lowered 3-50 times. The Km values for the monomeric substrate and the Km values for the micellar substrate were hardly affected in the case of five of the six mutants, but were considerably decreased when Trp was present at position 31. The results of these investigations point to a versatile role for the residue at position 31: involvement in the binding and orientating of monomeric substrate (analogs), involvement in the binding of the enzyme to micellar substrate analogs and possibly involvement in shielding the active site from excess water. PMID- 2217136 TI - Increased biological activity of a recombinant factor IX variant carrying alanine at position +1. AB - In attempts to improve the post-translational modification and processing of recombinant factor IX (FIX) we have altered the cDNA sequence encoding pre-pro FIX using site-directed mutagenesis and have expressed the variant cDNAs in BHK21 cells using a vaccinia-virus-derived vector. We find that substitution of the tyrosine residue at +1 for an alanine increases the biological activity of the recombinant molecules 2-fold. On the other hand, substitution of the proline at 3 for a valine results in no significant change to the specific activity of the protein. Other alterations to the N-terminus of the FIX proteins, in attempts to mimic other vitamin-K-dependent proteins, result in the failure to produce a secreted polypeptide. N-terminal sequence analysis of purified recombinant molecules reveals a correlation between specific activity and the efficiency of correct pro-sequence cleavage. gamma-Carboxylation analysis of purified recombinant proteins indicates that each molecule including unmutated FIX is completely gamma-carboxylated in this system. Thus the observed increase in biological activity of FIX variants containing an alanine at position +1 is not due to increased gamma-carboxylation but, at least in part, to more efficient pro peptide cleavage. PMID- 2217135 TI - Sequential protection-modification method for selective sulfhydryl group derivatization in proteins having more than one cysteine. AB - The method of Smith and Hartman [J. Biol. Chem., 263, 4921-4925 (1988)] for introducing the non-natural lysine analog, S-(2-aminoethyl)cysteine, into specific sites in proteins by alkylation of a genetically introduced cysteine with 2-bromoethylamine has been generalized to be applicable to proteins containing one or more endogenous cysteines. The target cysteine residue introduced at the active site of aspartate aminotransferase is protected by bound cofactor. The enzyme is partially unfolded in low concentrations of urea, and the non-active site cysteine residues derivatized by a reversible thiol protecting reagent. The active site cysteine is then exposed and alkylated in 6 M urea. Enzyme activity is regenerated by removal of the thiol protecting groups and refolding of the protein. PMID- 2217137 TI - Expression, purification and crystallization of penicillin G acylase from Escherichia coli ATCC 11105. AB - The penicillin acylase gene (pac) from Escherichia coli ATCC 11105 was cloned into pUC 9 and the resulting vector (pUPA-9), when transformed into E. coli strain 5K, allowed the constitutive overproduction of mature penicillin acylase when grown at 28 degrees C. The enzyme was purified from the periplasmic fraction of E. coli pUPA-9 by hydrophobic interaction chromatography and anion exchange. Crystals of penicillin acylase were grown in batch using polyethylene glycol 8000 as a precipitant. The crystals (space group P1) diffracted to beyond 2.3 A. PMID- 2217138 TI - Incorporation of crystallographic temperature factors in the statistical analysis of protein tertiary structures. AB - A method to identify statistically significant differences between equivalent atoms in two closely related protein X-ray crystallographic structures is described. This method uses the linear relationship found between the logarithm of the distance between equivalent atoms and their mean temperature factor to determine, by linear regression, the expected difference and variance. PMID- 2217139 TI - Predicting surface exposure of amino acids from protein sequence. AB - The amino acid residues on a protein surface play a key role in interaction with other molecules, determined many physical properties, and constrain the structure of the folded protein. A database of monomeric protein crystal structures was used to teach computer-simulated neural networks rules for predicting surface exposure from local sequence. These trained networks are able to correctly predict surface exposure for 72% of residues in a testing set using a binary model, (buried/exposed) and for 54% of residues using a ternary model (buried/intermediate/exposed). In the ternary model, only 11% of the exposed residues are predicted as buried and only 5% of the buried residues are predicted as exposed. Also, since the networks are able to predict exposure with a quantitative confidence estimate, it is possible to assign exposure for over half of the residues in a binary model with greater than 80% accuracy. Even more accurate predictions are obtained by making a consensus prediction of exposure for a homologous family. The effect of the local environment of an amino acid on its accessibility, though smaller than expected, is significant and accounts for the higher success rate of prediction than obtained with previously used criteria. In the absence of a three-dimensional structure, the ability to predict surface accessibility of amino acids directly from the sequence is a valuable tool in choosing sites of chemical modification or specific mutations and in studies of molecular interaction. PMID- 2217140 TI - Prediction of the disulfide-bonding state of cysteine in proteins. AB - The bonding states of cysteine play important functional and structural roles in proteins. In particular, disulfide bond formation is one of the most important factors influencing the three-dimensional fold of proteins. Proteins of known structure were used to teach computer-simulated neural networks rules for predicting the disulfide-bonding state of a cysteine given only its flanking amino acid sequence. Resulting networks make accurate predictions on sequences different from those used in training, suggesting that local sequence greatly influences cysteines in disulfide bond formation. The average prediction rate after seven independent network experiments is 81.4% for disulfide-bonded and 80.0% for non-disulfide-bonded scenarios. Predictive accuracy is related to the strength of network output activities. Network weights reveal interesting position-dependent amino acid preferences and provide a physical basis for understanding the correlation between the flanking sequence and a cysteine's disulfide-bonding state. Network predictions may be used to increase or decrease the stability of existing disulfide bonds or to aid the search for potential sites to introduce new disulfide bonds. PMID- 2217141 TI - The interpretation of site-directed mutagenesis experiments by linear free energy relations. AB - Fersht and co-workers have applied a linear free energy relation (Bronsted equation) to analyze site-directed mutagenesis experiments involving the enzyme tyrosyl-tRNA synthetase and have suggested that the Bronsted exponent is linearly correlated with the value of the reaction coordinate at the transition state. We point out that when the mutants differ solely through the formation or deletion of a hydrogen bond away from the reaction center, a linear free energy relation is expected only in limiting cases for which the Bronsted relation exponent is 0, 1 or infinity. The results may be correlated with a conformational coordinate but not with the development of the reaction coordinate per se. PMID- 2217142 TI - Molecular dynamics simulations of active site mutants of triosephosphate isomerase. AB - Molecular dynamics simulations of triosephosphate isomerase (TIM) and of some active site TIM mutants were performed in an attempt to elucidate possible interactions important for catalytic activity and binding. A variety of active site residues in TIM have been altered, resulting in all cases in decreases in catalytic activity. Second-site suppressor mutants were characterized for two of these active site mutants. The pseudorevertants have increased activity compared to the single mutant from which they were derived and, surprisingly, in both cases the increase in activity is a result of the replacement of an active site serine for proline. We performed simulations of wild-type TIM and the active site mutants with the substrate dihydroxyacetone phosphate bound both noncovalently and covalently. The noncovalent complexes were used to examine interactions important to binding while the covalent complexes are models of the transition state structure for enolization, which is the rate-determining step for the mutants. The difference between these two states, then, is related to the catalytic activity. We found various protein-substrate interactions that improved in the noncovalent mutant complexes, which correlates with the experimentally observed increase in binding affinity upon mutation. In the covalent complexes we observed improved electrostatic stabilization of the transition state upon introduction of Pro, which is also consistent with the experimental data. Our simulations reproduce the highly co-operative nature of the interactions in the active site and suggest that this approach may be useful for identifying particularly promising sites for mutation. PMID- 2217143 TI - Invariant amino acid replacement affects the dihydrofolate reductase function and its gene expression. AB - Three different forms of dihydrofolate reductase (DHFR) from Escherichia coli with amino acid replacements Thr35----Asp, Asn37----Ser and Arg57----His, and one form containing all three of these changes were obtained by oligonucleotide directed mutagenesis. These amino acids are on the surface of the protein and two of them (Thr35 and Arg57) are invariant for known sequences of DHFR. Conversion of Asn37----Ser has no effect on the functional activity or the protein level in the cells. The Thr35----Asp replacement leads to a sharp decrease in the protein level, while the addition of a DHFR inhibitor, trimethoprim (Tmp), to the growth medium increases the level of DHFR in the cells. There is a very small quantity of DHFR with all three amino acid changes. The addition of Tmp to the growth medium also leads to an increase in the mutant protein levels. The mutant with the Arg57----His replacement renders the cells sensitive to Tmp, but the level of DHFR is the same as for the wild-type protein. It is suggested that the invariant Thr35 is important for the stable conformation of DHFR whereas Arg57 is essential for protein activity. Various structural and functional aspects of these results are discussed. PMID- 2217144 TI - Mutational analysis of structure--activity relationships in human tumor necrosis factor-alpha. AB - To determine the region of human tumor necrosis factor-alpha (TNF-alpha), essential for cytotoxic activity against mouse L-M cells, single amino-acid substituted TNF-alpha mutant proteins (muteins) were produced in Escherichia coli by protein engineering techniques. An expression plasmid for TNF-alpha was mutagenized by passage through an E. coli mutD5 mutator strain and by oligonucleotide-directed mutagenesis. Approximately 100 single amino-acid substituted TNF-alpha muteins were produced and assayed for cytotoxic activity. The cytotoxic activities of purified TNF-alpha muteins, e.g. TNF-31T, -32Y, -82D, -85H, -115L, -141Y, -144K and -146E, were less than 1% of that of parent TNF alpha. These results indicate that the integrity of at least four distinct regions of the TNF-alpha molecule is required for full biological activity. These regions are designated as follows: region I, from position 30 to 32; region II, from position 82 to 89; region III, from position 115 to 117; region IV, from position 141 to 146. In addition, TNF-141Y could not completely compete with parent TNF-alpha for binding to the receptor. This demonstrates that region IV, and at least aspartic acid at position 141, must be involved in the TNF receptor binding site. PMID- 2217145 TI - Alteration in folding efficiency and conformation of recombinant human tumor necrosis factor-alpha by replacing cysteines 69 and 101 with aspartic acid 69 and arginine 101. AB - An analog of human tumor necrosis factor-alpha (TNF-alpha) was created involving the replacement of Cys69 with Asp and Cys101 with Arg. The solution structure and behavior of this analog were compared with the native protein. The analog exhibited a greatly decreased folding efficiency following dilution from urea, but essentially identical circular dichroic spectra in both the folded and unfolded states. The Stokes radius of the native and analog TNF-alpha in the folded state were identical, with the analog exhibiting a slight broadening of the eluting peak. The fluorescence emission spectrum of the native protein exhibits a plateau from 320 to 328 nm, while the spectrum of the analog consisted of a single peak with a maximum at 335 nm. The analog also had a 1.4-fold increase in the fluorescence intensity. Limited proteolysis of the analog resulted in only one of the two peptides seen following digestion of the native protein, and this product was less stable than the equivalent native protein fragment. The analog exhibited a 10-fold lower cytolytic activity than the native protein. These results demonstrated that the disulfide bond is not necessary for folding and activity, but are consistent with the analog having a looser, more flexible structure in solution than the native TNF-alpha. PMID- 2217146 TI - Improvement of nutritional value and functional properties of soybean glycinin by protein engineering. AB - Glycinin is one of the predominant storage proteins of soybean. To improve its functional properties (heat-induced gelation and emulsification) and/or nutritional value, the A1aB1b proglycinin subunit was modified on the basis of genetically variable domains suggested from the comparison of amino acid sequences of glycinin-type globulins from various legumes and nonlegumes and the relationships between the structure and the functional properties of glycinin. Thus, nucleotide sequences corresponding to each of the variable domains were deleted from the cDNA encoding the A1aB1b proglycinin, and a synthetic DNA encoding four continuous methionines was inserted into the cDNA region corresponding to each of the variable domains. Expression plasmids carrying the modified cDNAs were constructed and expressed in Escherichia coli strain JM105. Some of the modified proteins were accumulated as soluble proteins in the cells at a high level and self-assembled. They exhibited functional properties superior to those of the native glycinin from soybean, which establishes the possibility of creating theoretically designed novel glycinins with high food qualities. PMID- 2217148 TI - Closing in on the Aschoff body. PMID- 2217147 TI - Construction of a novel artificial-ribozyme-releasing plasmid. AB - A novel 'active-ribozyme-releasing system' was constructed, taking advantage of the consensus sequence of a new class of ribozyme. An active ribozyme sequence, targeted for the SFL1 gene (a yeast suppressor gene for flocculation) was fused just downstream of the T7 promoter. The 3' terminus of the first ribozyme was designed to be trimmed by the second ribozyme connected to the downstream of the first active ribozyme. In vitro experiments revealed that the active ribozyme targeted to SFL1 was successfully released by the action of the second ribozyme, subsequently cleaving the SFL1 mRNA at the predetermined site. Since the first active ribozyme with a defined 3'-terminus can be produced even when a circular DNA is used as a template, this kind of construct has a potential to release an 'active ribozyme' tailored to destroy a target gene (RNA) in vivo. Moreover, the second ribozyme in this construct can be utilized as a universal pseudo terminator for generation of any RNA transcripts inserted in place of the cassette portion of the first ribozyme. PMID- 2217149 TI - Splenic amyloidosis: correlations between chemical types of amyloid protein and morphological features. AB - Sixty-one autopsy cases of splenic amyloidosis were reviewed to assess the relationship between the morphological patterns and chemical types of amyloid protein. On the basis of immunohistochemical reactions of amyloid protein, the cases were classified into 34 cases of AA and 27 of AL amyloidosis. Amyloid deposition in the spleen was divided into three major sites: the red pulp, the white pulp, and blood vessels. Red pulp involvement by amyloid was noted in 52% of the AL cases but in none of the AA cases. White pulp amyloid deposition was found in 70% of the AL and 35% of the AA cases. This difference was statistically significant (P less than 0.001). On the other hand, vascular deposition of amyloid was invariably noted in all cases with AA or AL amyloidosis, affecting the AA cases rather severely. These results strongly suggest that the widely held concept of deposition of amyloid as predominantly vascular in AL amyloidosis and parenchymal in AA amyloidosis requires revision. Our findings indicate that parenchymal, especially the red pulp, involvement is a consistent feature of AL amyloidosis, whereas vascular involvement is a finding common to both types of systemic amyloidosis. PMID- 2217150 TI - Immunophenotypic and genotypic characterization of primary non-Hodgkin's lymphoma of the gastrointestinal tract. AB - Antigen receptor gene rearrangement studies have been applied to gastrointestinal (GI) lymphoid proliferations in only a limited number of cases, and their use and contribution to the diagnosis and characterization of GI lymphomas is unknown. We retrospectively studied 17 cases of primary GI lymphoma using fresh/frozen tissue with a combination of immunophenotypic and genotypic techniques. The vast majority of the neoplasms were B-cell lymphomas (88%) with rare T-cell tumors. The most common B-cell immunophenotype was IgM-kappa (40%), while five of the B cell lymphomas (33%) lacked surface light chain immunoglobulin. Immunophenotypic evidence of histiocytic differentiation was not identified. Clonality was confirmed in 59% (10/17) of the neoplasms by immunophenotyping and 88% (15/17) by antigen receptor gene rearrangement studies. All of the 15 B-cell lymphomas (100%) demonstrated clonally rearranged immunoglobulin gene rearrangement. The two lymphomas with T-cell immunophenotypes did not demonstrate T-cell receptor beta-chain gene rearrangement. Antigen receptor gene rearrangement data can be useful and may even be necessary in certain cases for the proper classification and/or diagnosis of GI lymphoid proliferations. PMID- 2217151 TI - Immunohistochemistry of Pneumocystis carinii infection. AB - Pneumocystis carinii is the pre-eminent pulmonary pathogen and leading cause of death in patients with acquired immunodeficiency syndrome (AIDS). The diagnosis of this organism depends upon the morphologic demonstration of the cyst wall, trophozoite, or sporozoite in specimens from the lower respiratory tract. A variety of histochemical stains have been used to identify P. carinii, each with considerable limitations in specificity. Extrapulmonary spread and unusually destructive pulmonary patterns associated with P. carinii, although once considered rare, are seen occasionally in patients with AIDS. Traditional stains have proven to be less reliable in extrapulmonary sites. In 13 patients with AIDS, we stained formalin-fixed paraffin-embedded autopsy lung and other visceral organ sections using monoclonal antibody 3F6 (Dako, Santa Barbara, CA) to P. carinii. The antibody stained P. carinii in the lungs of seven patients with P. carinii pneumonia by Gomori methenamine silver stain (GMS). Numerous aggregates of P. carinii cysts were marked within alveoli, as is usually seen with other stains. No antibody staining was present in autopsy lung sections from non-AIDS patients with viral, fungal, or bacterial pneumonia. Clinically occult extrapulmonary P. carinii infection was seen in 4/7 (57%) patients with P. carinii pneumonia at autopsy. Monoclonal antibody to P. carinii stained organisms in all four (100%) patients with disseminated disease, as compared with 1/4 (25%) staining with GMS. Antibody staining of P. carinii was demonstrated in sections of thyroid, adrenal, and carinal lymph node (one patient), esophagus (one patient), kidney (one patient), and heart, thyroid, kidney, adrenal, liver, stomach, pancreas, spleen, and bone marrow (one patient).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2217152 TI - Distribution pattern of follicular dendritic cells in low grade B-cell lymphomas of the gastrointestinal tract immunostained by Ki-FDC1p: a new paraffin-resistant monoclonal antibody. AB - This study surveyed 97 cases of low grade B-cell lymphoma (LGBL) of the gastrointestinal tract (GIT) by conventional morphology and immunohistochemistry, focusing on the most frequent subtype: the so-called LGBL of the mucosa associated lymphoid tissue (MALT). Special reference was made to the follicular dendritic cells (FDCs) selectively visualized by a new paraffin-resistant monoclonal antibody Ki-FDC1p. LGBL of the MALT accounted for 83 cases. The diagnosis was based on (a) a characteristic cytology, which included centrocytoid cells, a varying degree of plasma cell differentiation, and some blasts; (b) the presence of lymphoepithelial lesions; and (c) the occurrence of two types of follicles easily detectable with Ki-FDC1p. Some were restricted to the mucosa, contained normal germinal center cells, and were indistinguishable from reactive follicles. Others consisted of small clusters of FDCs, were randomly distributed throughout the tumor, and escaped detection in conventional stainings. Such small clusters of FDCs were found to be restricted to LGBL of the MALT, not occurring in other types of LGBL, and were interpreted as tumor-associated abortive follicles discernable from residues of reactive follicles due to their cellular constituents, localization, and distribution pattern. Eight cases showed closed sheets of blasts and were classified as high grade malignant lymphoma secondary to LGBL of the MALT. In two cases the LGBL of the MALT were restricted to the mucosa, in 31 cases the submucosa was also infiltrated, and in the remaining 50 cases the infiltration also involved deeper wall layers of the GIT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2217153 TI - Neural patterns in inflammatory bowel disease: an immunohistochemical survey. AB - The differential diagnosis of inflammatory bowel disease remains a significant diagnostic problem for surgical pathologists. Neural abnormalities, such as hypertrophy of nerve plexi, hyperplasia of ganglion cells, and ultrastructural axonal degeneration have been described in patients with regional enteritis. We performed an immunohistochemical survey of forty cases of regional enteritis, ulcerative colitis, nonspecific colitis, and normal colon. A panel of antibodies, directed against neuron-specific enolase, S-100 protein, synaptophysin, neurofilament protein, and nerve growth factor receptor, was utilized to evaluate the distribution of nerve fibers in paraffin-embedded tissue. Anti-synaptophysin and anti-nerve growth factor receptor highlighted small, arborizing nerve fibers in the mucosa, not apparent in the routinely stained sections. Intense staining of these fibers was observed in regional enteritis with antinerve growth factor receptor. This antibody may aid the discrimination of inflammatory bowel disease from other causes of colonic inflammation and facilitate the identification of regional enteritis in endoscopic biopsies. PMID- 2217154 TI - Typical and atypical carcinoid tumors of lung: a clinicopathologic and DNA analysis of 20 tumors. AB - Twelve typical carcinoid tumors (TCT) and eight atypical (malignant) carcinoid tumors (ACT) of the lung were studied for quantitative DNA content by image analysis in order to identify prognostic features. No correlation of any histologic variables of the TCTs and ACTs with abnormal DNA content were noted. Furthermore, it was concluded that although abnormalities of DNA content, particularly aneuploidy, are common in ACTs, DNA ploidy cannot be used independently to assess malignant potential. PMID- 2217155 TI - Asbestos bodies in pulmonary hilar lymph nodes. AB - Asbestos bodies (AB) have long been recognized in light microscopic (LM) sections of pulmonary hilar lymph nodes (LN) from patients with asbestos-related diseases, but the presence of AB on LM has not been correlated with the lung AB burden. The purpose of the present study was to determine whether AB in histologic sections of LN are indicative of heavy lung asbestos burdens. Twenty cases (17 with asbestosis, 15 with carcinoma of the lung, and two with malignant pleural mesothelioma) with at least one AB on a hilar LN section were identified. Bleach digestion of lung tissue in 15 cases demonstrated a median of 24,000 AB/g by LM and 44,000 AB/g by scanning electron microscopy. Digestion of hilar nodes demonstrated 21,800, 15,500, and 3,200 AB/g by LM in three cases which had lung burdens of 22,000, 481,000, and 5470 AB/g, respectively. A fourth LN specimen contained 322,000 AB/g in a case with no lung available to digest. Mean AB lengths in the LN in three cases were 48, 45, and 27 microns. Fourteen control cases of men over 50 without known asbestos exposure or asbestos-related disease had no AB in LN sections even after staining for iron. Among fourteen patients with parietal pleural plaques and an elevated lung asbestos body content, AB were observed in iron-stained LN sections in only two cases. These two patients had 3240 and 610 AB/g lung tissue, respectively (normal range 0 to 20 AB/g). We conclude that the finding of AB on a histologic section of hilar LN is generally indicative of a heavy lung AB burden.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2217156 TI - Methods in pathology. Immunophenotype of hairy cell leukemia in paraffin sections. AB - The immunophenotype of hairy cell leukemia (HCL) was investigated using 20 routinely fixed paraffin-embedded tissue sections (12 bone marrows, six spleens, one liver, one lymph node) from 12 patients known to have this disease. A panel of antibodies was used, including anti-leukocyte common antigen (anti-LCA), B lineage antibodies (LN2, MB2, L26), T-lineage reagents (MT1, UCHL1), monocytic (anti-cathepsin B) and myelomonocytic (anti-lysosyme, Mac 387) antibodies, and other less lineage-specific markers (anti-S-100, anti-alpha-1-antichymotrypsin (anti-alpha 1-ACT), anti-alpha 1-antitrypsin (anti-alpha 1-AT), anti-vimentin). Anti-LCA stained hairy cells in seven of the 12 bone marrows and consistently recognized hairy cells in the spleen, liver, and lymph nodes. Hairy cells generally reacted with B-lineage antibodies and were not labeled by T-lineage markers. No reactivity was noted with myelomonocytic antibodies, anti-S-100, anti alpha 1-ACT, or anti-alpha 1-AT. Vimentin was expressed in the majority of cases. Tartrate-resistant acid phosphatase reactivity was demonstrated in three of the 20 routinely processed tissue sections. These data suggest that immunohistochemical studies of hairy cell leukemia in routinely processed tissue may be useful in diagnostic hematopathology and surgical pathology. PMID- 2217157 TI - Current concepts of immunodeficiency disorders. AB - The technical developments in immunology and molecular biology during the 1970s, the growing use of organ transplantation during this period, and the abrupt emergence of AIDS in 1981 made the 1980s a fruitful period for investigating basic mechanisms of immunodeficiency. Now armed with powerful molecular biologic techniques, such as the polymerase chain reaction, we can identify specific genes and viruses that result in immunodeficiency. Complications associated with immunodeficiency, such as malignant lymphoma and opportunistic infections, have provided pathologists with opportunities for investigating the pathogenesis of this and other related diseases. An impetus for developing new diagnostic immunologic and molecular biological methods will be sustained during the 1990s. Pathologists working in the 21st century will be participants in the use of gene therapy for primary immunodeficiency diseases and for conquering AIDS. Perhaps with the declining threat of thermonuclear annihilation, we will tackle the largest cause of acquired immune deficiency, protein-calorie malnutrition. PMID- 2217158 TI - Leiomyomatous neoplasms of the lung. PMID- 2217159 TI - Molecular interactions in protein crystals: solvent accessible surface and stability. AB - The accessible surface areas of 58 monomeric and dimeric proteins, when measured in the crystalline environment, are found to be simply related to molecular weight. The loss of accessible surface when the proteins go from a free to their crystalline environment is well defined, implying that the hydrophobic interaction, which has been found to contribute to protein folding and stability in living systems, also contributes to protein crystal stability. PMID- 2217160 TI - Energetics of the structure and chain tilting of antiparallel beta-barrels in proteins. AB - The preferred structural pattern of antiparallel beta-barrels in proteins, described as the right-handed tilting of the peptide strands with respect to the axis of the barrel, is accounted for in terms of intra- and interchain interaction energies. It is related to the preference of beta-sheets for right handed twisting. Conformational energy computations have been carried out on three eight-stranded antiparallel beta-barrels composed of six-residue strands, in which L-Val and Gly alternate, and having a right-handed, a left-handed, or no tilt. After energy minimization, the relative energies of these structures were 0.0, 8.6, and 46.1 kcal/mol, respectively; i.e., the right-tilted beta-barrel is favored energetically, in agreement with anti-parallel beta-barrels observed in proteins. Tilting of the barrel is favored, relative to the nontilted structure, by both intra- and interstrand interactions, because tilting allows better packing of the bulky side chains. On the other hand, the energy difference between the left- and right-tilted barrels arises essentially from intrachain interactions. This is a consequence of the preference of beta-sheets for a right handed twist. Space limitations inside the barrel are satisfied if there is an alternation of bulky residues and residues with small or no side chain (preferably Gly) in neighboring positions on adjacent strands. Such a pattern is seen frequently in antiparallel beta-barrels of globular proteins. The computations indicate that a structure with Val...Gly pairs can be accommodated in a beta-barrel with no distortion. PMID- 2217161 TI - Protein stability and electrostatic interactions between solvent exposed charged side chains. AB - To investigate the contribution to protein stability of electrostatic interactions between charged surface residues, we have studied the effect of substituting three negatively charged solvent exposed residues with their side chain amide analogs in bovine calbindin D9k--a small (Mr 8,500) globular protein of the calmodulin superfamily. The free energy of urea-induced unfolding for the wild-type and seven mutant proteins has been measured. The mutant proteins have increased stability towards unfolding relative to the wild-type. The experimental results correlate reasonably well with theoretically calculated relative free energies of unfolding and show that electrostatic interactions between charges on the surface of a protein can have significant effects on protein stability. PMID- 2217163 TI - Crystallographic refinement of human serum retinol binding protein at 2A resolution. AB - Human serum retinol binding protein (RBP) in complex with retinol has been crystallographically refined to an R-factor of 18.1% with 2A resolution data. The protein topology results in an anti-parallel beta-barrel that encapsulates the retinol ligand. A detailed description of the protein and the binding site is provided. Our structural work has helped to define a family of proteins, many of which are carrier proteins for smaller ligand molecules. We describe the structural basis for the conservation of sequence within the family. PMID- 2217162 TI - Prediction of homologous protein structures based on conformational searches and energetics. AB - A "knowledge-based" method of predicting the unknown structure of a protein from a homologous known structure using energetics to determine a sidechain conformation is proposed. The method consists of exchanging the residues in the known structure for the sequence of the unknown protein. Then a conformational search with molecular mechanics energy minimization is done on the exchanged residues. The lowest energy conformer is the one picked to be the predicted structure. In the structure of bovine trypsin, the importance of including a solvation energy term in the search is demonstrated for solvent accessible residues, while molecular mechanics alone is enough to correctly predict the conformation of internal residues. The correctness of the model is assessed by a volume error overlap of the predicted structure compared to the crystal structure. Finally, the structure of rat trypsin is predicted from the crystal structure of bovine trypsin. The sequences of these two proteins are 74% identical and all of the significant changes between them are on external residues. Thus, the inclusion of solvation energy in the conformational search is necessary to accurately predict the structure of the exchanged residues. PMID- 2217164 TI - Hydrophobicity of amino acid subgroups in proteins. AB - Protein folding studies often utilize areas and volumes to assess the hydrophobic contribution to conformational free energy (Richards, F.M. Annu. Rev. Biophys. Bioeng. 6:151-176, 1977). We have calculated the mean area buried upon folding for every chemical group in each residue within a set of X-ray elucidated proteins. These measurements, together with a standard state cavity size for each group, are documented in a table. It is observed that, on average, each type of group buries a constant fraction of its standard state area. The mean area buried by most, though not all, groups can be closely approximated by summing contributions from three characteristic parameters corresponding to three atom types: (1) carbon or sulfur, which turn out to be 86% buried, on average; (2) neutral oxygen or nitrogen, which are 40% buried, on average; and (3) charged oxygen or nitrogen, which are 32% buried, on average. PMID- 2217165 TI - Revised 2.3 A structure of porcine pepsin: evidence for a flexible subdomain. AB - A revised three-dimensional crystal structure of ethanol-inhibited porcine pepsin refined to an R-factor of 0.171 at 2.3 A resolution is presented and compared to the refined structures of the fungal aspartic proteinases: penicillopepsin, rhizopuspepsin, and endothiapepsin. Pepsin is composed of two nearly equal N and C domains related by an intra dyad. The overall polypeptide fold and active site structures are homologous for pepsin and the fungal enzymes. The weak inhibition of pepsin by ethanol can be explained by the presence of one or more ethanol molecules, in the vicinity of the active site carboxylates, which slightly alter the hydrogen-bonding network and which may compete with substrate binding in the active site. Structural superposition analysis showed that the N domains aligned better than the C-domains for pepsin and the fungal aspartic proteinases: 107-140 C alpha pairs aligned to 0.72-0.85 A rms for the N domains; 64-95 C alpha pairs aligned to 0.78-1.03 A rms for the C domains. The major structural difference between pepsin and the fungal enzymes concerns a newly described subdomain whose conformation varies markedly among these enzyme structures. The subdomain in pepsin comprises nearly 100 residues and is composed of two contiguous segments within the C domain (residues 192-212 and 223-299). the subdomain is connected, or "hinged," to a mixed beta-sheet that forms one of the structurally invariant, active site psi-loops. Relative subdomain displacements as large as a 21.0 degrees rotation and a 5.9 A translation were observed among the different enzymes. There is some suggestion in pepsin that the subdomain may be flexible and perhaps plays a structural role in mediating substrate binding, determining the substrate specificity, or in the activation of the zymogen. PMID- 2217166 TI - The three-dimensional structure of recombinant bovine chymosin at 2.3 A resolution. AB - The crystal structure of recombinant bovine chymosin (EC 3.4.23.4; renin), which was cloned and expressed in Escherichia coli, has been determined using X-ray data extending to 2.3 A resolution. The crystals of the enzyme used in this study belong to the space group I222 with unit cell dimensions alpha = 72.7 A, b = 80.3 A, and c = 114.8 A. The structure was solved by the molecular replacement method and was refined by a restrained least-squares procedure. The crystallographic R factor is 0.165 and the deviation of bond distances from ideality is 0.020 A. The resulting model includes all 323 amino acid residues, as well as 297 water molecules. The enzyme has an irregular shape with approximate maximum dimensions of 40 x 50 x 65 A. The secondary structure consists primarily of parallel and antiparallel beta-strands with a few short alpha-helices. The enzyme can be subdivided into N- and C-terminal domains which are separated by a deep cleft containing the active aspartate residues Asp-34 and Asp-216. The amino acid residues and waters at the active site form an extensive hydrogen-bonded network which maintains the pseudo 2-fold symmetry of the entire structure. A comparison of recombinant chymosin with other acid proteinases reveals the high degree of structural similarity with other members of this family of proteins as well as the subtle differences which make chymosin unique. In particular, Tyr-77 of the flap region of chymosin does not hydrogen bond to Trp-42 but protrudes out in the P1 pocket forming hydrophobic interactions with Phe-119 and Leu-32. This may have important implications concerning the mechanism of substrate binding and substrate specificity. PMID- 2217167 TI - Human kidney amiloride-binding protein: cDNA structure and functional expression. AB - Phenamil, an analog of amiloride, is a potent blocker of the epithelial Na+ channel. It has been used to purify the porcine kidney amiloride-binding protein. Synthetic oligonucleotides derived from partial sequences have been used to screen a human kidney cDNA library and to isolate the cDNA encoding the human amiloride-binding protein. The primary structure was deduced from the DNA sequence analysis. The protein is 713 residues long, with a 19-amino acid signal peptide. The mRNA was expressed in 293-S and NIH 3T3 cells, yielding a glycoprotein (i) that binds amiloride and amiloride analogs with affinities similar to the amiloride receptor associated with the apical Na+ channel in pig kidney membranes and (ii) that is immunoprecipitated with monoclonal antibodies raised against pig kidney amiloride-binding protein. PMID- 2217168 TI - Prenylated proteins: synthesis of geranylgeranylcysteine and identification of this thioether amino acid as a component of proteins in CHO cells. AB - Prenylated proteins, labeled in the isoprenoid residue by growing CHO cells in medium containing [5-3H]mevalonate, were degraded by three different proteolytic procedures, enzymatic or alkaline hydrolysis as well as hydrazinolysis. The products thus obtained were analyzed by HPLC with chemically prepared all-trans geranylgeranylcysteine as a standard. About 10% of the radioactive products released by each lytic procedure showed the same chromatographic properties as geranylgeranylcysteine. This verifies the earlier conclusion, based on less direct evidence, that this thioether derivative of cysteine is a component of naturally occurring proteins. The finding of this modified amino acid as a product of hydrazinolysis indicates that it is a carboxyl-terminal amino acid and that it is not carboxyl-methylated. PMID- 2217169 TI - Down-regulation of a calmodulin-related gene during transformation of human mammary epithelial cells. AB - A human cDNA library obtained from cultured normal mammary epithelial cells (HMECs) was searched by subtractive hybridization for genes whose decrease in expression might be relevant to epithelial transformation. One clone identified by this procedure corresponded to a 1.4-kilobase mRNA, designated NB-1, whose expression was decreased greater than 50-fold in HMECs tumorigenically transformed in vitro after exposure to benzo[a]pyrene and Kirsten sarcoma virus. Sequence analysis of NB-1 cDNA revealed an open reading frame with a high degree of homology to calmodulin. NB-1 expression could be demonstrated by polymerase chain reaction amplification in normal breast, prostate, cervix, and epidermal tissues. The presence of NB-1 transcripts was variable in primary breast carcinoma tissues and undetectable in tumor-derived cell lines of breast, prostate, or other origins. NB-1 mRNA expression could be down-regulated in cultured HMECs by exposure to reconstituted extracellular matrix material, while exposure to transforming growth factor type beta increased its relative abundance. The protein encoded by NB-1 may have Ca2+ binding properties and perform functions similar to those of authentic calmodulin. Its possible roles in differentiation and/or suppression of tumorigenicity in epithelial tissues remain to be examined. PMID- 2217170 TI - Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ beta chain. AB - The presence of an amino acid other than aspartic acid at position 57 of the HLA DQ beta chain (non-Asp-57) is highly associated with susceptibility to insulin dependent diabetes mellitus (IDDM), whereas an aspartic acid at this position (Asp-57) appears to confer resistance to the disease. We hypothesize that the 30 fold difference in IDDM incidence across racial groups and countries is related to variability in the frequency of these alleles. Diabetic and nondiabetic individuals were evaluated in five populations, including those at low, moderate, and high risk. HLA-DQ beta genotype distributions among the IDDM case groups were markedly different (P less than 0.001), as were those among nondiabetic controls (P less than 0.001). Non-Asp-57 alleles were significantly associated with IDDM in all areas; population-specific odds ratios for non-Asp-57 homozygotes relative to Asp-57 homozygotes ranged from 14 to 111. Relative risk information from the case-control study and population incidence data were combined to estimate genotype-specific incidence rates for the Allegheny County, PA, Caucasians. These rates were used to predict the overall incidence rates in the remaining populations, which were within the 95% confidence intervals of the actual rates established from incidence registries. These results are consistent with the hypothesis that population variation in the distribution of non-Asp-57 alleles may explain much of the geographic variation in IDDM incidence. PMID- 2217171 TI - Pretreatment with cyclosporine and anti-interleukin 2 receptor antibody abrogates the anti-idiotype response in rat recipients of cardiac allografts. AB - A 10-day course with ART-18, a mouse monoclonal antibody (mAb) directed against the rat interleukin 2 receptor (IL-2R), prolongs the survival of (LEW x BN)F1 cardiac allografts in LEW recipients to approximately 3 weeks (acute rejection = 8 days, P less than 0.001). We examined host responses against ART-18 idiotype (Id) and mouse immunoglobulin in recipients immunomodulated with ART-18 mAb. Treatment with ART-18 elicited high titers of anti-Id antibodies 14 days after transplantation. However, naive rats given ART-18 before transplantation showed strong anti-Id responses as early as day 4 after engraftment, coinciding with abrogation of the treatment effect (graft survival, approximately 10 days). Preimmunization with irrelevant mouse IgG, which elicited high titers of anti IgG, did not influence the efficacy of ART-18 upon graft survival (17 days). The use of cyclosporin A (CsA) in conjunction with ART-18 prior to transplantation suppressed the anti-Id response and led to dramatic graft prolongation (greater than 58 days), with two of five grafts surviving indefinitely. This striking effect of CsA plus ART-18 pretreatment did not depend upon CsA per se, as grafts were rejected within 12 days in animals pretreated with CsA alone; in both groups CsA trough levels were comparable. Moreover, administration of CsA before transplantation in concert with control IgG (instead of ART-18) prompted rejection within 2-4 weeks. Thus, discrete interaction(s) between anti-IL-2R mAb and CsA prior to engraftment induces partial host unresponsiveness/tolerance to anti-IL-2R mAb treatment following transplantation and suppresses the neutralizing anti-Id responses, which results in long-term/permanent graft acceptance. This study provides a strategy to overcome the anti-Id response mounted by graft recipients that otherwise limits the efficacy of anti-IL-2R mAb treatment. PMID- 2217172 TI - Localization of phosphatidylinositol signaling components in rat taste cells: role in bitter taste transduction. AB - To assess the role of phosphatidylinositol turnover in taste transduction we have visualized, in rat tongue, ATP-dependent endoplasmic reticular accumulation of 45Ca2+, inositol 1,4,5-trisphosphate receptor binding sites, and phosphatidylinositol turnover monitored by autoradiography of [3H]cytidine diphosphate diacylglycerol formed from [3H]cytidine. Accumulated 45Ca2+, inositol 1,4,5-trisphosphate receptors, and phosphatidylinositol turnover are selectively localized to apical areas of the taste buds of circumvallate papillae, which are associated with bitter taste. Further evidence for a role of phosphatidylinositol turnover in bitter taste is our observation of a rapid, selective increase in mass levels of inositol 1,4,5-trisphosphate elicited by low concentrations of denatonium, a potently bitter tastant. PMID- 2217173 TI - Chitin synthase I and chitin synthase II are not required for chitin synthesis in vivo in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, the polysaccharide chitin forms the primary division septum between mother cell and bud. Two related enzymes, chitin synthase I and chitin synthase II (UDP-acetamido-2-deoxy-D-glucose:chitin 4-beta acetamidodeoxyglucosyltransferase, EC 2.4.1.16), have been identified and their structural genes, CHS1 and CHS2, respectively, have been cloned and sequenced. Gene disruption experiments led to the conclusion that CHS2 is essential for cell division [Silverman, S.J., Sburlati, A., Slater, M.L. & Cabib, E. (1988) Proc. Natl. Acad. Sci. USA 85, 4735-4739], whereas CHS1 is not. We repeated the disruption of CHS2 and determined that it is not essential for vegetative growth. The viability of chs1::HIS3 chs2::TRP1 spores is influenced by strain background and germination conditions. The double disruption mutant has no detectable chitin deficiency in vivo, as judged by quantitative assay and by staining cells with Calcofluor. Assay of membrane preparations from the double disruption mutant indicates the presence of chitin synthetic activity. Unlike the CHS gene products, this third activity is not stimulated by trypsin. Characterization of the double disruption mutant revealed abnormalities in morphology and nuclear migration. PMID- 2217174 TI - Productive human immunodeficiency virus infection levels correlate with AIDS related manifestations in the patient. AB - Mononuclear cells were obtained from 71 human immunodeficiency virus type 1 (HIV 1) seropositive subjects presenting and first visit either as asymptomatic or with minor symptoms and with CD4 lymphocytes greater than 550 per mm3 (group A, 35 patients) or as patients with AIDS, AIDS-related illnesses, or CD4 lymphocytes less than 400 per mm3 (group B, 36 patients). After 1-5 years of follow-up, 13 patients of group A had essentially retained their initial status (asymptomatics); the 22 others had suffered clinical or immunological deterioration (progressors). Frozen cells were thawed and submitted to lethal gamma-irradiation in vitro (4500 rads; 1 rad = 0.01 Gy) before they were cultured with normal phytohemagglutinin-stimulated lymphocytes to determine radiation resistant HIV expression ex vivo (R-HEV). HIV antigenemia correlated with R-HEV values in 142 samples (r = 0.92, P less than 0.001) but was a less sensitive predictor of disease than R-HEV. R-HEV was detected in all specimens from patients with major AIDS-related illnesses or HIV-associated CD4 lymphopenia. In 77% of the progressors from group A, R-HEV detection preceded the onset of AIDS associated disease or CD4 lymphopenia by 1 year (average). Conversely, R-HEV was low or was not detected in 36 sequential specimens from the 13 patients who remained asymptomatic over the following 2-5 years. Thus, persistently low HIV expression in vivo predicted a nondiseased state, whereas higher HIV expression levels seemed necessary for disease to occur. These data indicate that R-HEV is related to productive HIV infection in vivo, the latter acting as a determinant of AIDS-related illnesses. In view of this, measurement of HIV expression levels in the patient should be useful in antiviral efficacy trials. PMID- 2217175 TI - Incomplete synthesis of N-glycans in congenital dyserythropoietic anemia type II caused by a defect in the gene encoding alpha-mannosidase II. AB - Congenital dyserythropoietic anemia type II, or hereditary erythroblastic multinuclearity with a positive acidified-serum-lysis test (HEMPAS), is a genetic anemia in humans inherited by an autosomally recessive mode. The enzyme defect in most HEMPAS patients has previously been proposed as a lowered activity of N acetylglucosaminyltransferase II, resulting in a lack of polylactosamine on proteins and leading to the accumulation of polylactosaminyl lipids. A recent HEMPAS case, G.C., has now been analyzed by cell-surface labeling, fast-atom bombardment mass spectrometry of glycopeptides, and activity assay of glycosylation enzymes. Significantly decreased glycosylation of polylactosaminoglycan proteins and incompletely processed asparagine-linked oligosaccharides were detected in the erythrocyte membranes of G.C. In contrast to the earlier studied HEMPAS cases, G.C. cells are normal in N acetylglucosaminyltransferase II activity but are low in alpha-mannosidase II (alpha-ManII) activity. Northern (RNA) analysis of poly(A)+ mRNA from normal, G.C., and other unrelated HEMPAS cells all showed double bands at the 7.6 kilobase position, detected by an alpha-ManII cDNA probe, but expression of these bands in G.C. cells was substantially reduced (less than 10% of normal). In Southern analysis of G.C. and normal genomic DNA, the restriction fragment patterns detected by the alpha-ManII cDNA probe were indistinguishable. These results suggest that G.C. cells contain a mutation in alpha-ManII-encoding gene that results in inefficient expression of alpha-ManII mRNA, either through reduced transcription or message instability. This report demonstrates that HEMPAS is caused by a defective gene encoding an enzyme necessary for the synthesis of asparagine-linked oligosaccharides. PMID- 2217176 TI - Contraction of myofibrils in the presence of antibodies to myosin subfragment 2. AB - In a muscle-based version of in vitro motility assays, the unloaded shortening velocity of rabbit skeletal myofibrils has been determined in the presence and absence of affinity-column-purified polyclonal antibodies directed against the subfragment-2 region of myosin. Contraction was initiated by photohydrolysis of caged ATP and the time dependence of shortening was monitored by an inverted microscope equipped with a video camera. Antibody-treated myofibrils undergo unloaded shortening in a fast phase with initial rates and half-times comparable to control (untreated) myofibrils, despite a marked reduction in the isometric force of skinned muscle fibers in the presence of the antibodies. In antibody treated myofibrils, this process is followed by a much slower phase of contraction, terminating in elongated structures with well-defined sarcomere spacings (approximately 1 micron) in contrast to the supercontracted globular state of control myofibrils. These results suggest that although the unloaded shortening of myofibrils (and in vitro motility of actin filaments over immobilized myosin heads) can be powered by myosin heads, the subfragment-2 region as well as the myosin head contributes to force production in actively contracting muscle. PMID- 2217177 TI - Increased expression of a 58-kDa protein kinase leads to changes in the CHO cell cycle. AB - We have isolated and characterized cDNA encoding a human 58-kDa protein kinase that is homologous to the cell division control (CDC) protein kinases. This protein kinase also contains a unique N-terminal domain that may potentially regulate its function. Due to its relatedness to p34CDC2, the human p58 cDNA was overexpressed in CHO cells to determine the effect on the cell cycle. Elevated expression of p58 in these cells resulted in prolonged late telophase and early G1 phase of the cell cycle. These p58 overexpressors showed a significantly increased frequency of tubulin midbodies as well as significant increases in mitotic abnormalities. Thus, proper regulation of p58 protein kinase is essential for normal cell cycle progression in these cells. PMID- 2217178 TI - An inhibitor of the protease blocks maturation of human and simian immunodeficiency viruses and spread of infection. AB - The activity of the human immunodeficiency virus (HIV) protease is essential for processing of the gag-pol precursor proteins and maturation of infectious virions. We have prepared a peptidomimetic inhibitor, U-75875, that inhibited HIV 1 gag-pol protein processing in an essentially irreversible manner. Noninfectious virus particles produced in the presence of the drug contained gag precursors and were morphologically immature. In human peripheral blood mononuclear cells and in a continuous cell line, U-75875 completely blocked HIV replication; in the latter case, no spread occurred over a period of 4 weeks. U-75875, on a molar basis, was as potent as 3'-azido-3'-deoxythymidine in blocking HIV-1 replication in human lymphocytes and also inhibited HIV-2 and simian immunodeficiency virus proteases, demonstrating that it has broad activity. These results provide further evidence for the therapeutic potential of protease inhibitors in HIV infection. PMID- 2217179 TI - Cloning of the cDNA for human 12-lipoxygenase. AB - A full-length cDNA clone encoding 12-lipoxygenase (arachidonate:oxygen 12 oxidoreductase, EC 1.13.11.31) was isolated from a human platelet cDNA library by using a cDNA for human reticulocyte 15-lipoxygenase as probe for the initial screening. The cDNA had an open reading frame encoding 662 amino acid residues with a calculated molecular weight of 75,590. Three independent clones revealed minor heterogeneities in their DNA sequences. Thus, in three positions of the deduced amino acid sequence, there is a choice between two different amino acids. The deduced sequence from the clone plT3 showed 65% identity with human reticulocyte 15-lipoxygenase and 42% identity with human leukocyte 5 lipoxygenase. The 12-lipoxygenase cDNA recognized a 3.0-kilobase mRNA species in platelets and human erythroleukemia cells (HEL cells). Phorbol 12-tetradecanoyl 13-acetate induced megakaryocytic differentiation of HEL cells and 12 lipoxygenase activity and increased mRNA for 12-lipoxygenase. The identity of the cloned 12-lipoxygenase was assured by expression in a mammalian cell line (COS cells). Human platelet 12-lipoxygenase has been difficult to purify to homogeneity. The cloning of this cDNA will increase the possibilities to elucidate the structure and function of this enzyme. PMID- 2217180 TI - Determinants of the B-cell response against a transgenic autoantigen. AB - The failure to induce self-tolerance of simian virus 40 large tumor antigen (T antigen) expressed in the pancreatic beta cells of transgenic mice results in an autoimmune response against this protein and the cells that synthesize it. In every transgenic mouse with delayed onset of T-antigen expression and consequent nontolerance, B cells, T cells, and macrophages are attracted to and infiltrate the pancreatic islets. In contrast, the incidence, onset, and intensity of the B cell response to produce anti-T-antigen autoantibodies vary considerably with genetic background. Thus the initial attraction of lymphocytes to the cells synthesizing a non-self antigen can be separated from the activation of a B-cell response against it. Haplotypes of the major histocompatibility complex (MHC) differentially influence the character of the autoimmune response, with H-2d and H-2k conferring a high incidence of humoral autoimmunity. Additional non-MHC linked genes are also implicated in control of the B-cell response. PMID- 2217181 TI - Growth hormone and adipose differentiation: growth hormone-induced antimitogenic state in 3T3-F442A preadipose cells. AB - An additional activity for pituitary growth hormone is described--i.e., the in vitro induction of an antimitogenic state in murine 3T3-F442A preadipocyte fibroblasts. We previously developed a serum-free, hormonally defined medium permissive for the adipose differentiation of 3T3-F442A cells. When 3T3-F442A fibroblasts were maintained in serum-free medium without insulin but with growth hormone (2 nM), typical adipose differentiation did not occur. However, we found that growth hormone induced a state of cellular refractoriness to the mitogenic stimulus of fetal bovine serum as assayed by de novo DNA synthesis. The mitogen refractory condition (i.e., the antimitogenic state) was time-dependent (half maximal at approximately 2.5 days) and growth hormone concentration-dependent (half maximal and maximal at approximately 0.05 and 2.0 nM, respectively). The antimitogenic state was specifically induced by growth hormone and was not mediated by insulin-like growth factor I or prolactin. The growth hormone-induced antimitogenic state was completely reversible. The antimitogenic state was not induced by growth hormone in 3T3-C2 cells, a sister clone of 3T3 cells that exhibits essentially no adipose conversion. The kinetics for growth hormone dependent commitment to adipose differentiation and induction of the antimitogenic state were similar. We suggest a relationship of growth hormone induced antimitogenic state and the growth hormone-induced adipose differentiation of 3T3-F442A cells. PMID- 2217182 TI - Reassociation with beta 2-microglobulin is necessary for Kb class I major histocompatibility complex binding of exogenous peptides. AB - T lymphocytes recognize endogenously produced antigenic peptides in association with major histocompatibility complex (MHC)-encoded molecules. Peptides from the extracellular fluid can be displayed in association with class I and class II MHC molecules. Here we report that mature Kb class I MHC molecules bind peptides upon dissociation and reassociation of their light chain. Intact Kb heterodimers, unlike class II MHC molecules, are relatively unreceptive to binding peptides. This property may maintain segregation of class I and class II MHC-restricted peptides and has implications for the use of peptides as vaccines. PMID- 2217183 TI - A 140-base-pair repetitive sequence element in the mouse rRNA gene spacer enhances transcription by RNA polymerase I in a cell-free system. AB - We show that the repetitive 140-base-pair (bp) elements present in the spacer of mouse rRNA genes function as enhancers for RNA polymerase I. Attachment of these elements to the rDNA promoter stimulates rRNA synthesis both in vivo and in vitro. The cis-activating effect of the spacer repeats is orientation-independent and increases with increasing numbers of the 140-bp elements. Competition experiments demonstrate that the spacer repeats bind one or more of the transcription factors interaction with the rDNA promoter. Both the 140-bp elements and the core promoter act cooperatively and thus are functionally linked. The 60/81-bp enhancer repeats from Xenopus laevis rDNA compete for a murine transcription factor(s) and stimulate transcription often fused to the mouse rDNA promoter. The results indicate that despite the marked species specificity of rDNA transcription initiation, common factors may interact with both the rDNA promoter and the enhancer. PMID- 2217184 TI - Identification and preliminary characterization of protein-cysteine farnesyltransferase. AB - Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to exert their biological activity. Previous studies indicate that an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group. Inhibition of mevalonate synthesis reverts the abnormal phenotypes induced by the mutant RAS2Val-19 gene in Saccharomyces cerevisiae and blocks the maturation of Xenopus oocytes induced by an oncogenic Ras p21 protein of human origin. These results have raised the possibility of using inhibitors of the mevalonate pathway to block the transforming properties of ras oncogenes. Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we describe an enzymatic activity(ies) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro at the correct (Cys-186) residue. This farnesylating activity is heat-labile, requires Mg2+ or Mn2+ ions, is linear with time and with enzyme concentration, and is present in all mammalian cell lines and tissues tested. Gel filtration analysis of a partially purified preparation of protein farnesyltransferase revealed two peaks of activity at 250-350 kDa and 80-130 kDa. Availability of an in vitro protein farnesyltransferase assay should be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway. PMID- 2217185 TI - Mutagenesis of essential functional residues in acetylcholinesterase. AB - The cholinesterases are serine hydrolases that show no global similarities in sequence with either the trypsin or the subtilisin family of serine proteases. The cholinesterase superfamily includes several esterases with distinct functions and other proteins devoid of the catalytic serine and known esterase activity. To identify the residues involved in catalysis and conferring specificity on the enzyme, we have expressed wild-type Torpedo acetylcholinesterase (EC 3.1.1.7) and several site-directed mutants in a heterologous system. Mutation of serine-200 to cysteine results in diminished activity, while its mutation to valine abolishes detectable activity. Two conserved histidines can be identified at positions 425 and 440 in the cholinesterase family; glutamine replacement at position 440 eliminates activity whereas the mutation at 425 reduces activity only slightly. The assignment of the catalytic histidine to position 440 defines a rank ordering of catalytic residues in cholinesterases distinct from trypsin and subtilisin and suggests a convergence of a catalytic triad to form a third, distinct family of serine hydrolases. Mutation of glutamate-199 to glutamine yields an enzyme with a higher Km and without the substrate-inhibition behavior characteristic of acetylcholinesterase. Hence, modification of the acidic amino acid adjacent to the serine influences substrate association and the capacity of a second substrate molecule to affect catalysis. PMID- 2217186 TI - Direct determination of phospholipid lamellar structure at 0.34-nm resolution. AB - Low-dose, high-resolution electron microscopy combined with conventional direct phasing methods based on the estimates of triplet-structure invariants are used to determine phase values for all observed electron-diffraction-structure factor magnitudes from epitaxially oriented multilamellar paracrystals of the phosphospholipid 1,2-dihexadecyl-sn-glycerophosphoethanolamine. The reverse Fourier transform of these phase-structure factors is a one-dimensional electrostatic potential map that strongly resembles the electron-density maps calculated from similar x-ray-diffraction data. Determination of the phase values for the electron-diffraction data with structure invariants alone is nearly as successful as the combined use of two separate methods, assigning values to 13 of the 16 reflections--i.e., the electrostatic potential map closely resembles the one calculated with all data. PMID- 2217187 TI - Do voltage-dependent K+ channels require Ca2+? A critical test employing a heterologous expression system. AB - Removal of Ca2+ from the solution bathing neurons is known in many cases to alter the gating properties of voltage-dependent K+ channels and to induce a large, nonselective "leak" conductance. We used a heterologous expression system to test whether the leak conductance observed in neurons is mediated by voltage-dependent K+ channels in an altered, debased conformation. Voltage-dependent K+ channels were expressed in an insect cell line infected with a recombinant baculovirus carrying the cDNA for Drosophila Shaker "A-type" K+ channels. These expressed channels respond to low Ca2+ identically to voltage-dependent K+ channels in native neuronal membranes; upon removal of external Ca2+, Shaker K+ currents disappear and are replaced by a steady, nonselective leak conductance. However, control cells devoid of Shaker channels were free of any voltage-dependent conductances and did not generate a leak when external Ca2+ was removed. These results show that Ca2+ is essential for proper function of voltage-dependent K+ channels and is required to stabilize the native conformations of these membrane proteins. PMID- 2217189 TI - Purification and characterization of recombinant Rev protein of human immunodeficiency virus type 1. AB - Recombinant Rev protein of human immunodeficiency virus type 1 has been expressed in Escherichia coli and purified by ion-exchange and gel-filtration chromatography. Specific binding of the purified protein to the Rev-responsive element of the viral RNA is demonstrated. Physical characterization of the purified protein by circular dichroism and intrinsic fluorescence spectroscopy indicate that the protein preparation is suitable for structural analysis. Circular dichroism measurements show that the protein is approximately 40-45% alpha-helix. Tryptophan fluorescence measurements suggest that the single tryptophan residue is located near the surface of the protein. Gel-filtration chromatography of the protein indicates that it has an apparent molecular mass of 33,000 daltons. This suggests that the protein in solution forms a stable tetramer consisting of monomers having molecular mass of 13,000 daltons. PMID- 2217188 TI - Regulation of human renin expression in chorion cell primary cultures. AB - The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promotor linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3- to 6-fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. The transfected renin promoter (584 or 100 base pairs of 5'-flanking DNA) initiated at the correct start site in these cells and forskolin increased its expression 2.5- to 4-fold. Constructs containing renin 5'-flanking DNA linked to a heterologous promoter cotransfected into HeLa cells with either glucocorticoid or estrogen receptor expression vectors were not regulated by dexamethasone or 17 beta-estradiol. These results suggest that (i) the first 584 base pairs of the renin gene 5'-flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'-flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter. PMID- 2217190 TI - U1 small nuclear RNA plays a direct role in the formation of a rev-regulated human immunodeficiency virus env mRNA that remains unspliced. AB - rev-regulated expression of HIV-1 envelope proteins from a simian virus 40 late replacement vector was found to be dependent on the presence of a 5' splice site in the env mRNA in spite of the fact that this mRNA remains unspliced. When the 5' splice site upstream of the env open reading frame was deleted or mutated, expression of envelope protein was lost. RNA analysis of cells transfected with 5' splice-site mutants showed a dramatic reduction in the steady-state levels of env mRNA whether or not rev was present. Envelope expression could be restored in one of the 5' splice-site mutants by cotransfection with a plasmid expressing a suppressor U1 small nuclear RNA containing a compensatory mutation. These experiments show that U1 small nuclear RNA plays a direct and essential role in the formation of an unspliced RNA that is subject to regulation by rev. PMID- 2217191 TI - Direct detection of linker DNA bending in defined-length oligomers of chromatin. AB - Linker DNA, which connects between nucleosomes in chromatin, is short and, therefore, may be essentially straight and inflexible. We have carried out hydrodynamic and electron microscopic studies of dinucleosomes--fragments of chromatin containing just two nucleosomes--to test the ability of linker DNA to bend. We find that ionic conditions that stabilize the folding of long chromatin cause linker DNA in dinucleosomes to bend, bringing the two nucleosomes into contact. The results uphold a key prediction of the solenoid model of chromosome folding and suggest a mechanism by which proteins that are separated along the DNA can interact by direct contact. PMID- 2217192 TI - Counting dinosaurs: how many kinds were there? AB - Dinosaurs figure prominently in discussions of mass extinctions and evolutionary metrics, but their usefulness is hampered by archaic taxonomy, imprecise biostratigraphy, and imperfect preservation that bias our understanding of dinosaur diversity. A critical evaluation shows that of 540 genera and 800 species of dinosaurs proposed since 1824, 285 genera and 336 species are probably valid. Nearly half of all genera are based on a single specimen, and complete skulls and skeletons are known for only 20% of all dinosaurs. Dinosaurs are known from every continent. Countries with the greatest known diversity of dinosaurs are (in descending order) the United States, Mongolia, China, Canada, England, and Argentina; the greatest future increases may be expected from Argentina and China. Nearly half of all dinosaur genera are of latest Cretaceous age (Campanian or Maastrichtian). Estimates of the average duration of a dinosaur genus range from 5 million to 10.5 million years, with the most likely value about 7.7 million years. Dinosaurs evolved as rapidly as Cenozoic mammals. Global dinosaur diversity during the Campanian and Maastrichtian is estimated at 100 genera per stage, using a logistic model to estimate future discoveries. A model of increasing diversity and a bottleneck model compensate for the biasis in the preserved fossil record. The number of dinosaurs that have ever lived is estimated at 900-1200 genera. The fossil record of dinosaurs is presently about 25% complete. Dinosaurs disappeared in the Maastrichtian near the peak of their historic diversity. PMID- 2217193 TI - Adoptive transfer of autoimmune diabetes and thyroiditis to athymic rats. AB - We describe the induction of autoimmune diabetes, insulitis, and thyroiditis in athymic rats following injections of major histocompatibility complex compatible spleen cells. Lymphocytes with these capabilities were found in normal rats of the YOS, WAG, PVG, and diabetes-resistant BB strains, and in diabetes-prone BB rats. Adoptive transfer was facilitated by prior in vivo depletion of RT6.1+ regulatory T cells and in vitro mitogen activation of donor spleen cells. By RT6 depleting diabetes-resistant donors and using nude recipients, transfer of diabetes and thyroiditis was accomplished by using fresh, unstimulated spleen cells. The data suggest that organ-specific autoreactive cells may be present to various degrees but suppressed to a variable extent in many rat strains. The equilibrium between autoreactive and regulatory cells appears to determine the expression of autoimmunity. PMID- 2217194 TI - Wound-induced accumulation of mRNA containing a hevein sequence in laticifers of rubber tree (Hevea brasiliensis). AB - Hevein is a chitin-binding protein that is present in laticifers of the rubber tree (Hevea brasiliensis). A cDNA clone (HEV1) encoding hevein was isolated by using the polymerase chain reaction with mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea latex cDNA library as a template. HEV1 is 1018 base pairs long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a putative signal sequence of 17 amino acid residues followed by a 187-amino acid polypeptide. This polypeptide has two striking features. The amino-terminal region (43 amino acids) is identical to hevein and shows homology to several chitin-binding proteins and to the amino termini of wound-inducible proteins in potato and poplar. The carboxyl terminal portion of the polypeptide (144 amino acids) is 74-79% homologous to the carboxyl-terminal region of wound-inducible genes of potato. Wounding, as well as application of the plant hormones abscisic acid and ethylene, resulted in accumulation of hevein transcripts in leaves, stems, and latex but not in roots. PMID- 2217195 TI - Uric acid is a major antioxidant in human nasal airway secretions. AB - Airway mucosal surfaces are potentially subjected to a variety of oxidant stresses. Airway submucosal glands secrete a variety of compounds that may protect the airways from injury. Cholinergically induced nasal submucosal gland secretion has recently been found to contain a low molecular weight nasal antioxidant. In this report, the isolation and identification of this nasal secretory antioxidant are described. Concentrated, cholinergically induced human nasal secretions were fractionated through a 10-kDa sieve and subjected to DEAE anion-exchange chromatography. Fractions containing antioxidant activity were subjected to gel filtration with Bio-Gel P-2 gel (resolution range, 200-2000 Da). The resultant antioxidant fractions were then desalted by gel filtration over the same column equilibrated in HPLC-grade water, yielding only a single peak with antioxidant activity. The absorption spectrum of the purified antioxidant revealed peaks at 238 and 292 nm at pH 7. These peaks shifted to 230 and 280 nm in 0.1 M HCl and 226 and 296 nm in 0.1 M NaOH. Sodium borohydride reduction of the antioxidant had no effect on the UV absorption, whereas platinum-catalyzed hydrogenation ablated all absorption peaks. Uric acid had identical absorption peaks and showed the same chromatographic behavior as the nasal antioxidant activity on both gel filtration and DEAE columns. Uricase (which degrades uric acid) metabolized both uric acid and the purified antioxidant. Uric acid was shown to have antioxidant activity at concentrations greater than 1.5 microM. These data indicate that nasal secretions contain uric acid that serves as an antioxidant. PMID- 2217196 TI - Detection of heteroduplex DNA molecules among the products of Saccharomyces cerevisiae meiosis. AB - We have used denaturant-gel electrophoresis to provide a physical demonstration of heteroduplex DNA in the products of yeast meiosis. We examined heteroduplex formation at arg4-nsp, a G.C----C.G transversion that displays a moderately high level of postmeiotic segregation. Of the two possible arg4-nsp/ARG4 mismatches (G.G and C.C), only C.C was detected in spores from mismatch repair-competent (Pms1+) diploids. In contrast, C.C and G.G were present at nearly equal levels in spores from Pms1- diploids. These results confirm previous suggestions that postmeiotic segregation spores contain heteroduplex DNA at the site of the marker in question, that C.C is repaired less frequently than is G.G, and that the PMS1 gene product plays a role in mismatch correction. Combined with the observation that Pms1+ ARG4/arg4-nsp diploids produce 3 times more 3+:5m (wildtype:mutant) tetrads (+, +, +/m, m) than 5+:3m tetrads (+, +/m, m, m), these results indicate that, during meiosis, formation of heteroduplex DNA at ARG4 involves preferential transfer of the sense (nontranscribed) strand of the DNA duplex. PMID- 2217197 TI - Major histocompatibility complex haplotype studies in Ashkenazi Jewish patients with pemphigus vulgaris. AB - Of 26 Ashkenazi Jewish patients with pemphigus vulgaris, 24 (92.3%) carried the major histocompatibility complex (MHC) class II alleles HLA-DR4, DQw3, of which all were of the subtype DR4, DQw8. From studies of the patients and their families, haplotypes were defined. It was found that, of the patients who carried HLA-DR4, DQw8, 75% carried one or the other (and in one case, both) of two haplotypes [HLA-B38, SC21, DR4] or HLA-B35, SC31, DR4. The former is a known extended haplotype among normal Jews, with a frequency of 0.102, and the latter may also be an extended haplotype in this ethnic group, with a frequency of 0.017 among normal haplotypes from Jews. Of the remaining DR4-positive patients, all but one had a presumed D-region segment (defined as SC21, DR4, DQw8 or SC31, DR4, DQw8 with variable HLA-B) of these haplotypes. Only one patient had DR4, DQw8 without any other markers of the extended haplotypes. The number of homozygotes and heterozygotes for DR4, DQw8 was consistent with dominant but not recessive (P less than 0.01) inheritance of a class II or a class II-linked susceptibility gene for the disease. Since the disease is entirely attributable to the presence of an antibody to an intraepidermal intercellular cement substance, it is likely that the class II susceptibility gene (on [HLA-B38, SC21, DR4, DQw8], HLA-B35, SC31, DR4, DQw8, or their segments, in Jewish patients) controls the production of the antibody as a dominantly expressed immune response gene. PMID- 2217198 TI - DNA polymerase II is encoded by the DNA damage-inducible dinA gene of Escherichia coli. AB - The structural gene for DNA polymerase II was cloned by using a synthetic inosine containing oligonucleotide probe corresponding to 11 amino acids, which were determined by sequencing the amino terminus of the purified protein. The labeled oligonucleotide hybridized specifically to the lambda clone 7H9 from the Kohara collection as well as to plasmid pGW511 containing the SOS-regulated dinA gene. Approximately 1400 base pairs of dinA sequence were determined. The predicted amino-terminal sequence of dinA demonstrated that this gene encoded DNA polymerase II. Sequence analysis of the upstream region localized a LexA binding site overlapping the -35 region of the dinA promoter, and this promoter element was found to be only two nucleotides downstream from the 3' end of the araD gene. These results demonstrate that the gene order is thr-dinA (pol II)-ara-leu on the Escherichia coli chromosome and that the DNA polymerase II structural gene is transcribed in the same direction as the araBAD operon. Based on the analysis of the predicted protein, we have identified a sequence motif Asp-Xaa-Xaa-Ser-Leu Tyr-Pro-Ser in DNA polymerase II that is highly conserved among a diverse group of DNA polymerases, which include those from humans, yeast, Herpes and vaccinia viruses, and phages T4 and PRD1. The demonstration that DNA polymerase II is a component of the SOS response in E. coli suggests that it plays an important role in DNA repair and/or mutagenesis. PMID- 2217199 TI - Secondary structure of the ribosome binding site determines translational efficiency: a quantitative analysis. AB - We have quantitatively analyzed the relationship between translational efficiency and the mRNA secondary structure in the initiation region. The stability of a defined hairpin structure containing a ribosome binding site was varied over 12 kcal/mol (1 cal = 4.184 J) by site-directed mutagenesis and the effects on protein yields were analyzed in vivo. The results reveal a strict correlation between translational efficiency and the stability of the helix. An increase in its delta G0 of -1.4 kcal/mol (i.e., less than the difference between an A.U and a G.C pair) corresponds to the reduction by a factor of 10 in initiation rate. Accordingly, a single nucleotide substitution led to the decrease by a factor of 500 in expression because it turned a mismatch in the helix into a match. We find no evidence that exposure of only the Shine-Dalgarno region or the start codon preferentially favors recognition. Translational efficiency is strictly correlated with the fraction of mRNA molecules in which the ribosome binding site is unfolded, indicating that initiation is completely dependent on spontaneous unfolding of the entire initiation region. Ribosomes appear not to recognize nucleotides outside the Shine-Dalgarno region and the initiation codon. PMID- 2217200 TI - The gamma subunit of transducin is farnesylated. AB - Protein prenylation with farnesyl or geranylgeranyl moieties is an important posttranslational modification that affects the activity of such diverse proteins as the nuclear lamins, the yeast mating factor mata, and the ras oncogene products. In this article, we show that whole retinal cultures incorporate radioactive mevalonic acid into proteins of 23-26 kDa and one of 8 kDa. The former proteins are probably the "small" guanine nucleotide-binding regulatory proteins (G proteins) and the 8-kDa protein is the gamma subunit of the well studied retinal heterotrimeric G protein (transducin). After deprenylating purified transducin and its subunits with Raney nickel or methyl iodide/base, the adducted prenyl group can be identified as an all-trans-farnesyl moiety covalently linked to a cysteine residue. Thus far, prenylation reactions have been found to occur at cysteine in a carboxyl-terminal consensus CAAX sequence, where C is the cysteine, A is an aliphatic amino acid, and X is undefined. Both the alpha and gamma subunits of transducin have this consensus sequence, but only the gamma subunit is prenylated. Therefore, the CAAX motif is not necessary and sufficient to direct prenylation. Finally, since transducin is the best understood G protein, both structurally and mechanistically, the discovery that it is farnesylated should allow for a quantitative understanding of this post translational modification. PMID- 2217201 TI - Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential. AB - The experimental metastatic potential of 13762NF mammary adenocarcinoma clone MTLn3 was tested after pretreatment in serum-free medium containing transforming growth factor (TGF) beta 1 at 0-5000 pg/ml. Lung colonies were measured 2 weeks after inoculation in syngeneic F344 rats, and a bell-shaped dose-response curve with 2- to 3-fold increase in number of surface lung metastases was seen. Maximal enhancement occurred at the 50 pg/ml dose level. The effect was specific because addition of neutralizing anti-TGF-beta antibody blocked the stimulatory activity at all levels of TGF-beta 1 pretreatment, but when antibody was given alone, neutralizing anti-TGF-beta antibody had no effect on untreated cells. Increased metastatic potential appears to be from an increased propensity of cells to extravasate as tested in the membrane invasion culture system. MTLn3 cells penetrated reconstituted basement-membrane barriers 2- to 3.5-fold more than did untreated control cells, depending upon length of TGF-beta 1 exposure. Increased invasive potential is apparently due, in part, to a 2- to 6-fold increase in type IV collagenolytic (gelatinolytic) and a 2.4-fold increase in heparanase activity. TGF-beta 1 treatment of MTLn3 cells did not alter their growth rate or morphology in the presence of serum; however, growth was inhibited in serum-free medium. Likewise, adhesion to human umbilical vein endothelial cell monolayers or to immobilized reconstituted basement membrane or fibronectin matrices was unchanged. These results suggest that TGF-beta 1 may modulate metastatic potential of mammary tumor cells by controlling their ability to break down and penetrate basement-membrane barriers. PMID- 2217202 TI - Conservation of the primary structure, organization, and function of the human and mouse beta-globin locus-activating regions. AB - DNA sequences located in a region 6-18 kilobases (kb) upstream from the human epsilon-globin gene are known as the locus-activating region (LAR) or dominant control region. This region is thought to play a key role in chromatin organization of the beta-like globin gene cluster during erythroid development. The beta-globin LAR activates linked globin genes in transiently or stably transfected erythroleukemia cells and in erythroid cells of transgenic mice. Since the human beta-globin LAR is functional in mice, we reasoned that critical LAR sequence elements might be conserved between mice and humans. We therefore cloned murine genomic sequences homologous to one portion of the human LAR (site II, positions -11,054 to -10,322 with respect to the human epsilon gene). We found that this murine DNA fragment (mouse LAR site II) and sequences homologous to human LAR sites I and III are located upstream from the mouse beta-like globin gene cluster and determined that their locations relative to the cluster are similar to that of their human counterparts. The homologous site II sequences are 70% identical between mice and humans over a stretch of approximately 800 base pairs. Multiple core sequences with greater than 80% identity were present within this region. Transient and stable transfection assays of K562 erythroleukemia cells demonstrated that both human and mouse LAR elements contain enhancer activity and confer hemin inducibility on a linked human gamma-globin promoter. These results suggest that primary structural elements--and the spatial organization of these elements--are important for function of the beta-globin LAR. PMID- 2217203 TI - Purification of a 110-kilodalton cytosolic phospholipase A2 from the human monocytic cell line U937. AB - The major dithiothreitol-resistant phospholipase A2 activity present in the cytosol of U937 cells has been purified greater than 200,000-fold by sequential chromatography on phenyl-5PW, heparin-Sepharose CL-6B, high-performance hydroxylapatite, TSK-gel G3000-SW, and Mono Q columns. This 110-kDa cytosolic phospholipase A2 is distinct from the relatively small (14-kDa) dithiothreitol sensitive phospholipases A2 that are secreted from many cell types. This additional phospholipase A2 selectively hydrolyzes fatty acid at the sn-2 position of the glycerol and favors phospholipids containing arachidonic acid, which is the rate-limiting precursor for prostaglandin and leukotriene production. Interestingly, a greater than 5-fold increase in phospholipase A2 activity is noted as the calcium concentration increases from the levels found in resting cells to those observed in activated macrophages. We suggest that this enzyme and not the previously described secretory phospholipase A2 is activated by cytosolic effectors such as GTP-binding regulatory proteins and protein kinases to initiate the production of prostaglandins, leukotrienes, and platelet activating factor. To distinguish this cytosolic enzyme from the previously described secretory ones, we suggest referring to it as cPLA2 for cytosolic phospholipase A2 and collectively referring to the secretory phospholipases A2 as sPLA2s. PMID- 2217204 TI - Exocytic transport vesicles generated in vitro from the trans-Golgi network carry secretory and plasma membrane proteins. AB - We have developed a cell-free assay that reproduces vesicular budding during exit from the Golgi complex. The starting preparation for the in vitro system was a rat liver stacked Golgi fraction immobilized on a magnetic solid support by means of an antibody against the cytoplasmic domain of the polymeric IgA receptor. Vesicular budding was ATP, cytosol, and temperature dependent and was inhibited by 1 mM N-ethylmaleimide. Budding was maximum within 10 min and originated preferentially from the trans-Golgi. Exocytic transport vesicles immunoisolated from the total budded population were enriched in the mature forms of secretory and membrane proteins destined to the basolateral plasma membrane and were depleted in lysosomal enzymes and galactosyl-transferase activity. The finding that a major proportion (greater than 70%) of newly synthesized, siaylated secretory and transmembrane proteins is contained in a single population of post Golgi transport vesicles implies that, in a constitutively secreting cell, basolaterally destined proteins are sorted and packaged together into the same exocytic transport vesicles. PMID- 2217205 TI - Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction. AB - The binding of antigen to the multicomponent T-cell receptor (TCR) activates several signal transduction pathways via coupling mechanisms that are poorly understood. One event that follows antigen receptor engagement is the activation of inositol phospholipid-specific phospholipase C (PLC). TCR activation by antigen, lectins, or anti-TCR monoclonal antibody has also been shown to cause increases in tyrosine phosphorylation of TCR-zeta and other substrates, suggesting stimulation of protein tyrosine kinase (PTK) activity. A critical question is whether these two pathways, PLC and PTK, are independently activated or whether one initiates and/or regulates the other. In the former case, PLC activation could be coupled to the TCR via a GTP-binding protein (G protein). We have reported, however, that tyrosine phosphorylation of intracellular substrates precedes detection of PLC activation and intracellular calcium elevation, suggesting that inositol phospholipid turnover in T cells is initiated by a PTK pathway. In this study, we test this hypothesis by treating T cells with the drug herbimycin A. We demonstrate that this agent inhibits substrate tyrosine phosphorylation, TCR-mediated inositol phospholipid hydrolysis, and calcium elevation. In contrast, under these conditions G-protein-mediated PLC activity, as tested by addition of aluminum fluoride, remains intact. Furthermore, whereas herbimycin treatment prevents TCR-mediated interleukin 2 production and interleukin 2 receptor expression, phorbol ester-induced effects are substantially resistant to herbimycin. The drug thus appears to abrogate TCR mediated signaling without affecting distal signaling mechanisms. PMID- 2217206 TI - Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCR alpha beta + and TCR gamma delta + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion. AB - Individuals infected by the human immunodeficiency virus type 1 (HIV-1) demonstrate progressive depletion and qualitative dysfunction of the helper T4 (CD4+) cell population. Mechanisms proposed for attrition of CD4+ T cells include direct cytopathicity of these mature cells following infection as well as infection of early T-lymphocyte progenitors. The latter mechanism could lead to failure to regenerate mature functioning CD4+ T cells. The present study determines the susceptibility of thymocytes at various stages of maturity to infection with HIV-1. Various normal thymocyte populations were inoculated with HIV-1, including unfractionated (UF), CD3- CD4- CD8- ["triple negative" (TN)], CD4+ CD8+ ["double positive" (DP)] thymocytes, and thymocyte populations obtained by limited dilution cloning. Cultures were studied for the presence of HIV-1 DNA by polymerase chain reaction in addition to examination for reverse transcriptase activity. We determined that transformed T-cell and thymocyte cell lines completely lacking CD4 were not susceptible to infection by HIV-1, whereas all of the following lines were: UF thymocytes (70-90% CD4hi+); DP thymocytes (99% CD4hi+); TN thymocytes (0% CD4hi+); and TCR alpha beta +, TCR gamma delta +, or CD16+ CD3- (natural killer) thymocyte clones expressing variable levels of CD4 and representing the progeny of TN thymocytes. [TCR alpha beta + and TCR gamma delta + refer to the chains of the T-cell antigen receptor (TCR), and CD4hi refers to a strong rightward shift (greater than 30 linear channels) of the CD4 curve on flow cytometric analysis compared with control.] Monoclonal antibodies (mAbs) to CD4 (T4a epitope) but not to CD3 (T3) were capable of blocking infection of mature and immature CD4hi+ thymocytes. Moreover, anti-CD4(T4a) mAbs also inhibited infection of CD4hi- TN thymocytes, indicating that these T-cell precursors--despite their apparent "triple negativity" (CD3- CD4hi- CD8-)- expressed sufficient CD4 molecules to become infected. Cell sorter analysis with a panel of CD4 mAbs demonstrated a mean shift of the mean fluorescence channel (MFC) with CD4 mAbs on TN thymocytes of 6 +/- 4 MFC units. Thus, intrathymic T cell precursors and their progeny representing many stages of T-cell ontogeny are susceptible to infection by HIV-1, including early TN thymocytes, which express very low levels of CD4. Infection of multiple stages and multiple subsets of the T-cell lineage in man, mediated via the CD4 molecule, may explain the inability of the T-cell pool to regenerate in the setting of progressive HIV infection. PMID- 2217207 TI - Identification of three related human GRO genes encoding cytokine functions. AB - The product of the human GRO gene is a cytokine with inflammatory and growth regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity. We have identified two additional genes, GRO beta and GRO gamma, that share 90% and 86% identity at the deduced amino acid level with the original GRO alpha isolate. One amino acid substitution of proline in GRO alpha by leucine in GRO beta and GRO gamma leads to a large predicted change in protein conformation. Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. A 122-base pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones confirm that the three forms are derived from related but different genes. Only one chromosomal locus has been identified, at 4q21, by using a GRO alpha cDNA clone that hybridized to all three genes. Expression studies reveal tissue-specific regulation as well as regulation by specific inducing agents, including interleukin 1, tumor necrosis factor, phorbol 12-myristate 13-acetate, and lipopolysaccharide. PMID- 2217208 TI - Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma. AB - Mutational inactivation of the retinoblastoma gene (RB) is found in all retinoblastomas and in a subset of other human neoplasms, including sarcomas of bone or soft tissue and carcinomas of lung or breast. Exogenous copies of wild type RB have been shown to suppress the tumorigenicity of several types of tumor cells with endogenous RB mutations, including a previously described human prostatic carcinoma cell line. To further support a role for RB inactivation in the genesis of prostate cancer, seven primary or metastatic prostate carcinoma specimens were examined for evidence of RB mutation. By the use of immunoblot analysis and immunostaining of histologic sections, RB-encoded protein was readily detected in tumor cells of five specimens, was equivocally detected in one specimen, and was apparently absent from tumor cells of one specimen. RB mutations in the latter case were precisely characterized as (i) a deletion of 103 nucleotides containing transcriptional start sites and (ii) loss of the second RB allele. The 103-base-pair deletion was sufficient to abolish the promoter activity of upstream DNA sequences in a heterologous expression system. These results (i) demonstrate that RB can be inactivated in vivo by mutation of its promoter, (ii) confirm the existence of RB mutations in some human prostate carcinomas, and (iii) suggest the use of immunohistochemical methods to screen for RB mutations in clinical samples of common adult neoplasms. PMID- 2217209 TI - Chemical carcinogenesis: too many rodent carcinogens. AB - The administration of chemicals at the maximum tolerated dose (MTD) 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 half--of all chemicals tested (whether natural or synthetic) are indeed rodent carcinogens. We conclude that at the low doses of most human exposures, where cell killing does not occur, the hazards to humans of rodent carcinogens may be much lower than is commonly assumed. PMID- 2217210 TI - Dietary pesticides (99.99% all natural). 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 American diet are chemicals that plants produce to defend themselves. Only 52 natural pesticides have been tested in high-dose animal cancer tests, and about half (27) are rodent carcinogens; these 27 are shown to be present in many common foods. We conclude that natural and synthetic chemicals are equally likely to be positive in animal cancer tests. We also conclude that at the low doses of most human exposures the comparative hazards of synthetic pesticide residues are insignificant. PMID- 2217211 TI - Nature's chemicals and synthetic chemicals: comparative toxicology. AB - 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 (nature's pesticides) and that these defenses are effective against both natural and synthetic toxins. Synthetic toxins such as dioxin are compared to natural chemicals, such as indole carbinol (in broccoli) and ethanol. Trade-offs between synthetic and natural pesticides are discussed. 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) undermines current regulatory efforts to protect public health from synthetic chemicals based on these tests. PMID- 2217213 TI - Isothermal, in vitro amplification of nucleic acids by a multienzyme reaction modeled after retroviral replication. PMID- 2217214 TI - We must begin to value our part time nurses. PMID- 2217215 TI - From text book to reality. Student nurse training needs in stoma care. AB - Student nurses on a stoma care placement can feel out of their depth. Guidance from experienced nurses can help them acquire the practical and emotional skills required, and gain new confidence. PMID- 2217212 TI - Steroid-receptor fusion of the human immunodeficiency virus type 1 Rev transactivator: mapping cryptic functions of the arginine-rich motif. AB - The human immunodeficiency virus type 1 (HIV-1) transactivator Rev is a nuclear protein that regulates expression of certain HIV-1 transcripts by binding to an RNA target element (the RRE) present in these transcripts. A short arginine-rich sequence in Rev contains the signals required to direct this protein into nuclei, where it associates preferentially with nucleoli. We created a steroid-inducible transactivator by fusing Rev with the steroid-binding domain of the glucocorticoid receptor (GR). This Rev/GR protein remains inactive in the cytoplasm when steroids are absent, but it enters the nucleus and initiates transactivation within minutes after exposure to dexamethasone. Although the GR moiety is sufficient to transport Rev/GR into nuclei, mutation of certain residues in the arginine-rich region blocks nucleolar localization and also inhibits transactivation. We find that other mutations in this region, however, can abolish the function of Rev/GR without affecting its localization; the latter phenotype may reflect a specific defect in binding of the RRE. PMID- 2217216 TI - We must assess the care we give. Nursing practices in invasive procedures. AB - Hospital acquired infections are a common phenomenon, particularly in patients who are undergoing invasive procedures. However, the rate of infection can be cut down by thorough assessment of nursing care. PMID- 2217217 TI - Opioids: routes of administration. PMID- 2217218 TI - When should you take your tablets? Teaching elderly people about their medication. AB - In the last issue it was shown that many elderly people fail to comply with medication. Here, a framework is suggested to educate hospital patients before discharge. PMID- 2217219 TI - A major contributor. Evaluation of Comfeel Pressure Relieving Dressing. PMID- 2217220 TI - Mums and Dads need care too. Supporting parents of babies in neonatal units. AB - New parenthood can be traumatic and stressful at the best of times, but for parents with a baby in a neonatal unit, the experience can be much more difficult to deal with. The support received from unit staff can make all the difference. PMID- 2217221 TI - The three levels of nursing care. PMID- 2217222 TI - Obliteration of the circadian rhythm of intraocular pressure in Graves' ophthalmopathy. PMID- 2217223 TI - Chronobiology in laboratory medicine: principles and clinical applications illustrated from measurements of neutral steroids in saliva. AB - A number of chronobiological principles, as they pertain to the practice of laboratory medicine, have been discussed. Without doubt, salivary steroid assays are valuable tools for use in clinical studies, not necessarily as a single time qualified sample but more often as a series of samples that will describe the underlying endocrinological time-structure. It is also important to appreciate that melatonin, certain drugs, and many dietary constituents such as phyto oestrogens, are among the myriad of substances that can be monitored, and so hold great promise for the chronobiologist interested in the use of saliva as a sampling medium, both in the present and in the future. PMID- 2217224 TI - Improved therapeutic index of cisplatin analogue: B-85-0040 by circadian timing. AB - 1. B-85-0040 is a new cisplatin analogue with dose limiting myelosuppression. 2. The maximum tolerated dose ranges between 300 and 525 mg/kg for single i.p. bolus injection in mice. 3. Its toxicity is circadian-stage dependent with optimal tolerance between 16 and 17 hours after lights on. 4. B-85-0040 is active in L1210 leukemia. Anti-tumor activity seems to be unrelated to the circadian stage of treatment. Optimal drug timing can therefore increase its therapeutic index. PMID- 2217225 TI - Potential value of salivary steroids in chronoepidemiological and endocrine related studies. AB - Experience from Institute studies has clearly demonstrated the advantages of salivary steroids in clinical endocrinological research and their potential value in chronoepidemiological studies of many kinds that may involve hormones. Of course, the examples and suggestions for areas of research involve many more covariates than those mentioned; but sufficient evidence has been presented to indicate the chronobiological potential of salivary steroid assays in studies of mental health, aggression and behaviour, stress, the endocrine changes occurring from birth to old age and those relating to endocrine cancer. The pioneering studies of Halberg et al (1981) and Haus et al. (1987) have demonstrated the feasibility of carrying out international epidemiological studies as they relate to breast cancer risk and studies of the general population. The potential value of salivary steroid assays in clinical, physiological and epidemiological studies is judged to be considerable. PMID- 2217226 TI - Lack of circadian variation in renal function in the obese rat: influence of continuous food and water intake. PMID- 2217228 TI - Circadian rhythm of glucocorticoid receptors in human peripheral leukocytes and their reactivity to glucocorticoids. AB - 1) There exists a CR of GR in human leukocytes, PMN, and monocytes with the peak values from 0400 to 0800 hr and the trough values between 2300 and 0000 hr. The difference between them was significant statistically. 2) The FI of the chemotactic migration rate of PMN by cortisol also showed diurnal changes which were synchronous with that of GR. This indicates that the CR of GR may be of functional significance. 3) In Cushing's syndrome, the CR of GR was normal in spite of the fact that the CR of plasma cortisol was disturbed. This indicates the independency of the CR of GR from that of cortisol. 4) In apoplexy caused by brain ischemia, the CR of GR was abolished in patients with basal lesions but preserved when the lesions were located in the cerebral cortex. These results strongly suggest that the main "circadian pacemaker" of GR is located in the basal brain, most probably in the suprachiasmatic nuclei as has been suggested for rodents. PMID- 2217229 TI - A circaoctohoran rhythm of urine epinephrine excretion in man. PMID- 2217227 TI - Circadian rhythms of total renin and active renin concentrations in normotensive young subjects. PMID- 2217230 TI - Circadian parameters of 17-hydroxycorticosteroids and electrolyte rates during the menstrual cycle. PMID- 2217231 TI - Thyroid volume variation during the menstrual cycle in healthy subjects. PMID- 2217233 TI - Chronobiological evaluation of 24-hour lipid and lipoprotein changes in middle aged males. PMID- 2217232 TI - A circaseptan rhythm (about 7 day) in some metabolic circulating variables. PMID- 2217234 TI - Serum cholinesterase (CE) activity and lipid levels in hyperlipidemic rats. PMID- 2217235 TI - Possible relationship between intergroup variability in circadian, circamensual and circannual rhythms in man. PMID- 2217236 TI - The effects of time of trauma patient presentation on emergency department utilization. AB - All three posed temporal questions have now been answered as being positive factors in ED utilization: 1) Major and minor trauma patients should be expected to present at ED in largest numbers around 17.67 hr each day and especially during the month of August. Some types of major trauma (i.e., medical, surgical, psychiatric patients) require longer periods for stabilization in the ED before being discharged to the appropriate care unit. Such patients also tend to arrive later at the ED than do patients destined for MICU, SICU, or CCU. 2) Changing the trauma ordinance did not affect the temporal effects noted above but did produce a strikingly large influx of minor trauma presents relative to major trauma presents during the post-ordinance period. 3) The nature and number of the ED staffing should be reviewed and probably changed in order to reflect the large influx of trauma presents during the 1600 to 2400 hr shift. The third question has the most impact on ED utilization during the "Golden Hour of Trauma". Individual emergency departments must cope with the fact that the maximum demand on facilities and professional health expertise will normally occur during the hours from 1600 to 2400 each day. Some EDs have recognized this increased demand and have responded by maximizing the quantity and quality of their staff on the 1600 to 2400 hr shift. These data indicate that more EDs should follow suit as soon as possible. PMID- 2217237 TI - Nonparametric testing of melatonin characteristics as potential markers of breast cancer risk. AB - On the average, the circadian A of ML is larger in clinically healthy women at high vs. low RDBC. The original finding was made without numerical sampling on data from a relatively small group of women sampled systematically around the clock and the year. It was hence of further interest to see whether the risk related difference can be corroborated by numerical resampling, i.e., by BS, a fairly general, usually computerintensive technique used for estimating the sampling distribution of an estimator or statistic (i.e., a quantity computed from the data). For BS of circannual parameters, one here assumes that 1) circadian As (obtained by the fit of a 24-hour cosine curve by linear least squares) are correlated for any given subject from season to season; and 2) deviations of each circadian A from the average are random. The method then estimates the characteristics of harmonic components, ordered by P-values obtained by linear least-squares analysis involving a test of the assumption of zero A for each special component. Results from BS validate differences in circadian A of ML between the low and high RDBC groups throughout the year. The use of BS serves to introduce inferential considerations into discriminant analysis and to test results obtained with very limited samples sizes, before embarking upon the actual labor-intensive, costly resampling required in circannual and circadian work. BS is a procedure recommended for broad routine use in non-parametric hypothesis testing and biomedical signal simulation. The re evaluation of ML data by BS provides further inferential statistical validation of the finding as a first complement, not substitute, for additional sampling in order to assess a possibly important component of a test battery for breast cancer risk. PMID- 2217238 TI - Circadian rhythm disturbances in neurological patients with chronic hypothermia. AB - 1) We investigated the circadian rhythms of BT and sleep-wakefulness in 8 neurological patients who showed chronic low BT. Their etiologies were varied. 2) Their thyroid functions were normal, but their hypothalamic functions were disturbed endocrinologically to various degrees. 3) Their temperature-elevation system was able to function when they suffered from infectious disease. 4) Six patients had circadian rhythm disturbances of BT and sleep-wakefulness. This fact suggests that there is a close relationship of BT regulation and control of its rhythm, and also a close association of 2 pacemakers, namely, that of sleep wakefulness and that of BT. PMID- 2217239 TI - Nocturnal asthma, its pathogenesis and treatment. AB - Many chronobiologic and cyclic environmental factors are implicated in the pathophysiology of nocturnal asthma. A better understanding of these interrelating processes is essential for an optimization of medications for asthma. A reasonable therapeutic approach for the management of nocturnal asthma is the use of inhaled beta-agonists routinely, on a daily basis, and if symptoms persist, the use of an appropriate SR theophylline scheduled once-daily in the evening. Inhaled cromolyn sodium and corticosteroid therapy, properly timed to rhythms, may be warranted to control inflammation and stabilize the airways. PMID- 2217240 TI - Structural and ultrastructural circadian features in rat exocrine pancreas. PMID- 2217241 TI - Ambulatory cardiovascular monitoring of healthy adults in Rochester, Minnesota: chronobiologic assessment. AB - To serve as a tentative reference group for clinical health, 107 adults measured their systolic (S) and diastolic (D) blood pressure (BP) with an ambulatory Del Mar Avionics monitor (Irvine, California). Data were collected over approximately 24 hours at 7.5-minute intervals during waking and at 15-minute intervals during sleep. An echocardiogram served to determine the left ventricular mass (LVM), septal wall thickness (SWT), posterior wall thickness (PWT), ejection fraction (EjFr), and left atrial size (LAS). Each data series was analyzed by single cosinor. A statistically significant circadian rhythm (P less than 0.05) was found in 96 subjects (89.7 percent) for SBP and in 86 subjects (80.4 percent) for DBP. A population-mean cosinor reveals a highly significant circadian rhythm (P less than 0.001) for both variables in men (n = 44) as well as in women (n = 63), with an acrophase around 14:15. The double circadian amplitude, a measure of the total predictable change within a day, averages 10 (women) and 11 (men) mm Hg for DBP and 14 (women) and 17 (men) mm Hg for SBP. The midline-estimating statistic of rhythm (MESOR) of SBP is found to be higher for men (125 mm Hg) than for women (120 mm Hg), P = 0.018, whereas no difference in MESOR is found for DBP (71 mm Hg). A statistically significant correlation with age is found for the MESOR of SBP in both men (r = 0.352; P = 0.018) and women (r = 0.336; P = 0.007). The MESOR of SBP is also found to correlate with LVM in men (r = 0.300; P = 0.046), but not in women (r = 0.181; P = 0.153), whereas the MESOR of DBP correlates with LVM in women (R = 0.316; P = 0.011) but not in men (r = 0.117; P = 0.543). A positive correlation is also found between the MESOR of SBP and SWT as well as with EjFr, which is more prominent in women; between the MESOR of DBP and LAS, which is more prominent in men; and a negative correlation is found for women but not men between the circadian amplitude of both SBP and DBP and EjFr. Blood pressure excess (in mm Hg x h; hyperbaric index, briefly HBI; Halberg et al., 1984) was computed by comparing each profile to the upper 95 percent time-varying prediction limit of healthy peers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2217243 TI - Agreement between consecutive ambulatory 24-hour blood pressure and heart rate profiles in Japanese hospital staff. PMID- 2217242 TI - Chronobiological blood pressure assessment of 334 normotensive Japanese. PMID- 2217244 TI - Peri-awakening rise of blood pressure revisited: a linear "speed" of increase in unit time. PMID- 2217245 TI - Enhancement of respiratory sinus arrhythmia by moderate exercise. PMID- 2217246 TI - Chronobiologic assessment of deviant human blood pressure: an invitation for improvements. PMID- 2217247 TI - Secular or circannual effects of placebo and melatonin on murine breast cancer? PMID- 2217248 TI - Clinical evaluation of chronobiological blood pressure data validated by echocardiogram. PMID- 2217249 TI - A two-dimensional index for the assessment of elevated blood pressure. PMID- 2217250 TI - Chronobiological characteristics of 75 patients with essential hypertension. PMID- 2217251 TI - Relationship between circadian rhythm of blood pressure and left ventricular function in hypertensive patients. PMID- 2217252 TI - Enhancing the physiologic effectiveness of cardiac stimulators in heart rhythms' management using chronobiology. PMID- 2217253 TI - Twenty-four hour TXB2 production in unstable angina. PMID- 2217254 TI - Chronobiologic evaluation of the efficacy of a new calcium antagonist, nicardipine hydrochloride, in 'essential hypertension'. PMID- 2217255 TI - Chronesthesia to cardiac glycosides of patients with cardiac failure. PMID- 2217256 TI - Circadian characteristics of cardiovascular rhythms in pregnancy. PMID- 2217257 TI - Chronobiologic approach to pregnancy-induced hypertension and individualized assessment of low-dose aspirin for pre-eclampsia prevention. PMID- 2217258 TI - Can the chronobiological approach better evaluate the relationship between diabetes mellitus and arterial hypertension? AB - This work evaluates by a chronobiological approach the relationship between arterial hypertension and diabetes mellitus. Sixteen type II (non-insulin dependent) diabetic hypertensive males (age 50-60 years, BMI 26 +/- 1, without nephropathy) were selected for the study. Blood pressure (BP) was considered borderline, mild or moderate, systolic and/or diastolic by a single measurement (occasional measurement) according to the Report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (1984). Then both dynamic ambulatory BP through a 24-hr span (5300 ABPS Spacelabs) and an oral glucose-tolerance test (100 gm) with serum glucose and insulin measures were carried out. Total insulin area (TIA) and total glucose area (TGA) were computed. Blood-pressure values were analyzed by the Cosinor method, and then percent time of elevation (PTE) and the hyperbaric impact (HBI) were calculated. A statistically significant positive correlation was found between TIA and the mesors of both systolic BP/diastolic BP (p less than 0.05) and HBI (p less than 0.05 and p less than 0.01, respectively). PMID- 2217259 TI - Menstrual-cycle-synchronized circaseptan rhythms of temperature in cancer associated breast tissue. PMID- 2217260 TI - Relationship of heart rate, respiratory rate, and arterial blood pressure rhythms in a mechanically ventilated patient to environmental variables in an intensive care unit. PMID- 2217261 TI - Circadian rhythm of ischemic episodes in patients with and without previous myocardial infarction. PMID- 2217262 TI - Ultradian and infradian components in onset of acute myocardial infarction (AMI). PMID- 2217263 TI - Stroke incidence: circadian and circaseptan (about weekly) variations in onset. PMID- 2217264 TI - Circadian rhythm alteration in HIV infected subjects. PMID- 2217266 TI - Further extensions of the cosinor approach to problems of the pharmaceutical industry. AB - The resolution of a more complex time structure than that described by the useful first approximation of a single cosinor is suggested herein. The cosinor serves the purpose of parsimony in the case of sparse and short time series, yet it can be usefully extended by assessing the variations in rhythm characteristics for treatment timing in the clinic rather than only for research. PMID- 2217265 TI - Persistence of circadian rhythms in hematologic and biochemical functions except for melatonin, following a single 12 hour prolongation of the light span. PMID- 2217267 TI - Loss of the progesterone-associated metabolic rhythm in cancer-associated breast tissue. PMID- 2217269 TI - Chronotoxicologic studies on dichlorphos in mice and humans. PMID- 2217268 TI - A preliminary report of circadian effects of interleukin-2 (IL-2) on the activity of enzymes of intermediary metabolism of mice. AB - Since it previously has been reported that IL-2 has profound circadian dependent effects upon DNA synthesis in the liver of mice (Scheving et al., 1988; Tsai et al., 1988) the effects of IL-2 on enzyme activities were studied. The objective was to determine the effect of IL-2 when administered at different times to mice who were fed ad libitum, and standardized to 12 h of light alternating with 12 h of dark. Three groups were injected intraperitoneally with either 1 or 4 mg/kg of IL-2, one group was given the vehicle only. The treatment time for each dose and the vehicle was a 2 h into the light for one group and the other was at 2 h into the dark span. Subgroups of 5 mice were killed 4, 8, 12, 16, 20, 24, and 30 h after each treatment, livers were taken and frozen to await preparation and analysis of enzyme activities by our standard procedures. When treatment was in the light span IL-2 had no statistically significant effect on enzymes of lipid, carbohydrate or amino acid metabolism. On the contrary when treatment was given in the dark span IL-2 produced statistically significant increases in enzymes of glycolysis, and lipid synthesis beginning 8 h after treatment (changes ranged from 20 to 43%) with both the higher and lower doses (higher doses always yielded higher activities), and these activities continued to increase through the 24 h post-treatment span (changes ranged from 42 to 64%). At 30 h, activities were returning to normal levels. Amino acid metabolism, on the other hand, was decreased during these post-treatment times (the range of decrease was from 18 to 44%). Thus, we report for the first time that the duration of time, pathway affected, as well as the magnitude of the effect seen and the dosage of IL-2 were all circadian-stage dependent even with two time point samplings. We believe, however, that these two time points represent different critical extremes in liver metabolism, but studies with denser sampling are planned. Interleukin-2 was generously supplied by Cetus Corp. of Emeryville, CA. PMID- 2217270 TI - Circannual rhythm in response of renin release to calcium deprivation in isolated rat glomeruli. PMID- 2217271 TI - Calcitonin: chronotherapeutic effect on osteopenia in the ovariectomized rat. AB - This chronotherapeutic study has revealed no clear evidence to support the concept that calcitonin promotes bone formation in intact or OVX'd rats. Rather, the efficacy of CT-impaired bone resorption appeared to be optimal in OVX'd rats treated during the daytime, and least effective during the first half of the environmental dark span. These findings indicate a benefit for calcitonin chronotherapy in this animal model where the cellular kinetics resemble those documented in early development of postmenopausal osteoporosis. PMID- 2217272 TI - Circadian stage dependent 125I-insulin binding in the liver and epididymal fat of the mouse. PMID- 2217273 TI - Circadian rhythms of T lymphocyte subpopulations and cortisol in kidney and heart transplantation. PMID- 2217274 TI - Menstrual amplitude reduction in averaged basal body temperature data from pre menopausal breast cancer patients. PMID- 2217275 TI - The treatment of mild hypertension with mepindolol: a chronobiological evaluation. PMID- 2217276 TI - Blood pressure and heart rate in pregnancy: comparison between health and pathologic conditions. PMID- 2217277 TI - Chronobiologic approach to blood pressure during pregnancy and early extrauterine life. PMID- 2217278 TI - Circadian rhythms of tumor markers in breast cancer patients. PMID- 2217279 TI - Endpoints of chronobiologic cardiovascular monitoring during pregnancy for planning exercise and assessing effects. AB - The chronobiologic question is raised whether exercise may be indicated for the pregnant woman as a general prophylactic measure and, if so, whether it should be timed according to rhythms and stage of pregnancy. This question, recently considered by others without chronobiologic focus, is here reviewed against the background of results from ongoing chronobiologic studies of blood pressure (BP) and heart rate (HR) in pregnancy. During pregnancy, the MESORs and circadian amplitudes of systolic (S), mean arterial (MA) and diastolic (D) BP are correlated with a questionnaire-assessed cardiovascular risk score. Such results were found under noisy ordinary conditions of life without accounting for effects of activity. They are group results, and as such require further work before they can contribute to identifying individuals at high risk in particular need of intervention, such as exercise. The dependence of exercise effects upon circadian rhythms should also prompt the use of rhythmometry at all ages for timing exercise, for gauging its effects and eventually for the optimization of fitness training for the population as well as for peak performance. PMID- 2217280 TI - Individualized assessment of blood pressure and heart rate late in human pregnancy. PMID- 2217281 TI - Reference limits for 24 hour patterns of gestational blood pressure in normotensive pregnant women monitored under standardized conditions. PMID- 2217282 TI - Circaseptan and circannual modulation of circadian rhythms in neonatal blood pressure and heart rate. PMID- 2217283 TI - Human neonatal infradian, notably circannual, blood pressure and heart rate rhythms, gender and cardiovascular disease risk. PMID- 2217284 TI - Spontaneous motor activity and sleep-wake cycles in low-risk preterm infants. PMID- 2217285 TI - Oral temperature rhythmometry and substantial within-day variation in zidovudine levels following steady-state dosing in human immunodeficiency virus (HIV) infection. PMID- 2217286 TI - Circadian frequency synchronization with difference in phase of maternal and neonatal blood pressure. PMID- 2217287 TI - Sleep duration preferences in 4 to 14 month old babies. PMID- 2217289 TI - Circadian rhythms of total renin and active renin concentrations in normotensive young subjects. PMID- 2217288 TI - Circadian and seasonal variation in iodine excretion in children in an endemic goiter area. PMID- 2217290 TI - Seasonal characteristics of and age at menarche. AB - Several patterns in menarche are evident over time and across populations which vary by ethnicity, socioeconomic status and altitude of residence: peak occurrence of menarche in January and August with a possible minor peak in April; troughs in the occurrence of menarche to either side of the peak months; and secular trends in season and age patterns of menarche. Contradictory patterns in season of menarche with respect to age at menarche and season of menarche with respect to season of birth are still unresolved. Further research is yet required to evaluate the role of the variety of endogenous and exogenous variables and their interactions on menarche in order to more fully develop an appropriate understanding of the chronobiology of developmental and reproductive phenomena in women and their dependence upon environmental quality and temporal cues. PMID- 2217291 TI - Circannual rhythm of plasma growth hormone in girls (but not boys) with constitutional short stature. AB - GH concentrations (in ng/ml) were determined by radioimmunoassay in plasma obtained at about 3-hour intervals during a 24-hr sampling span from 40 boys and 14 girls of short stature, 6-14 years of age, living on a diurnal waking (approximately 07:00 to approximately 22:00), nocturnal resting routine. Circadian rhythm parameters were first computed by the single and population mean cosinor fits of a 24-hour cosine curve. Circadian parameter comparisons revealed an intergroup difference between the genders in A (P = .012) and, perhaps, in M (P = .078), but not in 0 (P = .957). In the search for circannual variability, individual circadian Ms were fitted by LLS with a 1 year cosine curve. The LLS harmonic analysis shows a circannual rhythm for the girls (P = .037; M = 8.54; A = 5.38; 0 = -214 degrees from January 1), but not for the boys. Moreover, a 3.5 months prominent component was also found for both the individual circadian Ms (P = .010) and As (P = .012) when all subjects are considered for analysis irrespectively of gender. These infradian characteristics complement circadian differences in GH between boys and girls and must be taken into account in the development of any protocol for studies of GH responses to GH-releasing hormone in children with short stature. PMID- 2217292 TI - Temporal patterns of hot flashes in natural and surgically-induced menopause. PMID- 2217293 TI - Seasonal variation in the incidence of congenital malformations in San Miguel de Allende, Mexico. PMID- 2217294 TI - Similar circadian characteristics of serum glucose in boys and girls of short stature. AB - In the absence of any gastroenterologic complaint, circadian variations characterize serum GL in 22 boys and 7 girls of short stature, 6-14 years of age, living on a diurnal waking (approximately 07:00 to approximately 22:00), nocturnal resting routine, consuming the usual hospital diet. Blood was drawn at about 3-hour intervals during a 24-hour sampling span and serum stored frozen at 60 degrees C until radioimmunoassay for GL concentration (in mg/dl). Circadian rhythm parameters were computed by the single and population mean cosinor fits of a 24-hour cosine curve. A parameter-comparison of data from the two genders indicates similar circadian M, A and 0 for both groups. The Ps for a comparison of Ms, As, 0s and (A,0) pairs are .635, .183, .385 and .308, respectively. The larger differences between genders were found for the circadian A. In human beings, differences in the A of a rhythm are associated with differences in the probable development of several civilization diseases. In this sense, evaluation of risk by appropriately designed questionnaires should next complement blood sampling in groups of children differing in age, gender, health or ethnicity, with the purpose in mind of deriving prediction regions for assessment of health, risk or disease. PMID- 2217295 TI - Infradian characteristics of plasma cortisol in children of short stature. AB - CT concentrations (in micrograms/dl) were determined by radioimmunoassay in plasma obtained at about 3-hour intervals during a 24-hour sampling span from 42 boys and 16 girls of short stature, 6-14 years of age, living on a diurnal waking (approximately 07:00 to approximately 22:00), nocturnal resting routine. Circadian rhythm parameters were first computed by the single and population mean cosinor fits of a 24-hour cosine curve. A parameter-comparison shows similar circadian rhythm parameters for both genders, the Ps for a comparison of Ms, As, 0s and (A,0) pairs being .69, .14, .73 and .32, respectively. In the search for infradian variability, individual circadian Ms were first fitted by LLS. The LLS harmonic analysis shows prominent components with periods of 8, 7, 4, 3 and 1 months, with ordering P-values of .031, .011, .009, .018 and .024, respectively. The rhythm parameters thus obtained were used as initial values for the NLLS method. This approach only detects the circaseptrigintan (7 months) component, with estimated period, M, A and 0 of 5023.96 hours, 10.32 micrograms/dl, 3.34 micrograms/dl and -273 degrees, respectively. These not anticipated infradian characteristics of the adrenal cortisol cycle may constitute quantitative parameters in dealing with risk in health and may serve to monitor any possible progression of a condition into a disease. PMID- 2217296 TI - Circadian rhythm in human activity objectively quantified by actigraphy. PMID- 2217297 TI - Circadian reference data for men in fifth decade of life. AB - These results are meant to serve as chrono-biologically-defined reference values for healthy adult men in their fifth decade of life. A thorough statistical analysis of these data is being prepared for presentation elsewhere. A rigorous comparison with results obtained when these same men were in their 20's and again in their 30's may help us to document the kinds and extent of changes in circadian rhythm characteristics (MESOR, amplitude and/or acrophase) which may occur with aging. PMID- 2217299 TI - Circannual variation of human mortality in Texas. PMID- 2217298 TI - Chronobiological evaluation of heart rate characteristic as a possible predictor of biological aging. PMID- 2217301 TI - Circaseptan-circadian rhythmic changes in corneal mitoses of Louvain rats. PMID- 2217300 TI - Effects of high and low protein diets on circadian rhythms in %S and %G2+M stages of the cell cycle in rat corneal epithelium studied by DNA flow cytometry. PMID- 2217302 TI - Human psychological circadian rhythms as behavioral messengers. PMID- 2217303 TI - On the frequency of "diurnal variations of mood" in psychiatric patients- seasonal aspects. PMID- 2217305 TI - Evidence that the pacemaker controlling activity rhythms is shortened in male thyroparathyroidectomized (TPX) rats: similarities to the effects of estradiol in females. AB - The experiments described here demonstrate that TPX and TX male rats display shorter free-running activity rhythms and higher activity levels compared to intact males. Neither effect could be duplicated in TPX females. The patterns in activity period, range of entrainment, and levels of activity observed in TPX males closely resembles that reported in intact females or OVX females treated with estradiol. These data suggest the possibility of a common mechanism linking circadian alterations produced by estradiol and thyroid state. This hypothesis needs to be tested, as does the question of whether thyroid hormones or calcitonin are responsible for the TPX and TX results. If thyroid hormones prove to be the causal agents, opposing effects of thyroid hormones and estradiol on adrenergic receptors provide a possible common mode of action for these agents on the circadian system. Disparate results from rat and hamster studies concerning the influence of thyroid state on activity rhythms suggest the possibility of species differences in this level of circadian organization. Thus, caution should be exercised in extrapolating results to other species, including humans. PMID- 2217304 TI - Chronoendocrine assessment of the risk of developing depressive disorders. AB - Chronoepidemiology studies alterations of biologic rhythms with several frequencies as harbingers and possibly determinants of the risk of developing certain diseases. Along these lines, a method for pattern discrimination, the so called "monotest", involving the leave-one-out technique for the estimation of the PM, is here used in the search for classifiers of personality. By this method, chronoendocrine relations of a DPP are explored in 12 plasma hormones sampled around the clock in 4 seasons on a small number of clinically and psychologically healthy women, 29-36 years of age. Subjects were separated in two groups by scores for DPP of the Mini-Mult, an abbreviated version of the Minnesota Multiphasic Personality Inventory. Discriminant analysis singles out plasma aldosterone as the primary classifier for DPP in winter. In spring, the best classifiers include 17-OH progesterone and insulin, whereas in the summer the circadian amplitude of 17-OH progesterone classifies best. Finally, the identified classifiers in the fall are DHEA-S, estradiol and estrone. In clinical health, hormones are thus sensitive in ordering people who, according to questionnaires, are at different risk of developing emotional disorders. Results also illustrate the need to consider the intermodulation of circadian and circannual rhythms, whenever endocrine variables are being determined in human plasma. PMID- 2217306 TI - Circadian rhythm of melatonin release from pineal hypothalamus and pituitary in hypertensive rats. PMID- 2217307 TI - Evidence that therapeutic alterations of a circadian rhythm for gastric emptying response may be possible. PMID- 2217308 TI - Rhythms of stimulated gastric acid secretion in duodenal ulcer (DU). PMID- 2217309 TI - Effect of chronic caloric restriction on hepatic enzymes of intermediary metabolism in aged B6C3F1 female mice. AB - Caloric restriction (CR) extends maximum life span and significantly retards the rate of occurrence of most age-associated degenerative diseases. The effect of CR in female mice on several hepatic enzymes was examined after 33 month old mice were killed at either the onset of dark, the onset of light or the mid-dark span. Animals had been singly caged with 12 hr of light followed by 12 hr of dark. All feeding was in the early dark span. CR mice were given 60% of the caloric intake of ad libitum fed mice throughout their lives (CR was initiated at 14 weeks of age). Livers were frozen to await preparation and then analysis for 14 enzymes of intermediary metabolism by our standard procedures. Enzymes of gluconeogenesis and amino acid metabolism were increased at all times due to CR. Enzymes of glycolysis and lipid metabolism were decreased at all times. However, maximum differences between ad libitum and CR mice occurred during the mid-dark span (this is the time of normal acrophase in younger mice). Circadian variation was lost and mesors changed for nearly all enzymes measured from mice that had been fed ad libitum. CR mice were found to maintain circadian variation of activities and activity profiles were similar to those seen in younger ad libitum fed mice. These observations suggest that the mechanism through which CR elicits its effects may involve a circadian component. PMID- 2217310 TI - Circadian periodicity of gastrointestinal peptides in male rats after orchidectomy and hormone replacement. PMID- 2217311 TI - Impact of time and feeding habits on lipid levels in Zucker obese rats. AB - The influences of time and hyperphagia on cholesterol, triglyceride, glucose and insulin levels were compared in the obese Zucker rat and compared to its lean litter-mates. Following a 28 day acclimation period in a 12 hr light/dark cycle (08-20-08) animal facility, blood samples were obtained every 2 hr in both obese and lean rats over a 24 hr period (N = 48; Dec 1988); serum was measured enzymatically for cholesterol, triglyceride and glucose and by radioimmunoassay for insulin and cortisol levels. Synchronization with other animal studies was established by endogenous serum cortisol measurements (acrophase 18-20 HALO in both groups). Cholesterol, triglyceride, insulin and glucose concentrations were significantly greater per time interval in obese vs. lean rats. No circadian pattern was observed in glucose concentrations in either rat group. Insulin levels peaked in both rat groups during the dark cycle; however, glucose and insulin levels were not correlated. Cholesterol concentrations were unchanged over time in obese as well as lean rats. Although triglyceride levels showed an acrophase at 13 HALO in lean rats, no circadian pattern was found in obese rats. Triglyceride levels remained elevated throughout the 24 hour period in obese rats whereas significant increases were observed in lean rats during the dark cycle. The present results suggest that triglyceride levels, and not insulin and cholesterol levels, are most likely dependent on feeding and activity patterns. PMID- 2217312 TI - Circadian rhythm of gastric pH in patients with healed ulcer under placebo and constant-rate ranitidine infusions. PMID- 2217313 TI - Infradian variation in the incidence of giardiasis assessed by linear-nonlinear rhythmometry. AB - The analysis of biological time series necessarily involves mathematical and physiologic techniques for purposes of data collection and interpretation, respectively. To assess a biologic rhythm in a given time series, one can first fit a cosine curve with a fixed period to the data by LLS. When the period is unknown or when there is more than one significant period, with no integral relation among them, LLS have to be replaced by NLLS. In applying the NLLS method, initial values for all the parameters in the model are first estimated by LLS. These are usually the overall M and the periods, As and 0s corresponding to each component found to be statistically significant by LLS. This combined approach was used in the search for infradian variability in the incidence of GD, the most common gastrointestinal parasitic disease in the USA at the present time. Monthly totals in ten consecutive years (1977 to 1986) of cases of GD detected in Minnesota (USA) were first fitted by LLS. The linear harmonic analysis shows the anticipated 1-year synchronized circannual rhythm with a period of 8766 hours (P less than .001) and other prominent components with periods of 7 (P = .038), 6 (P = .003), 5 (P = .001) and 3 (P less than .001) years, which were not anticipated. The rhythm parameters thus obtained are then used as initial values for the nonlinear method. Components of 5, 3. and 1 years are then detected by the NLLS approach, that also gives estimates and 95% confidence intervals for the period, the M, the A, and the 0 of each significant component. Of very great interest are infradian changes also seen time macroscopically in other data on numbers of waterborne cases and outbreaks of GD. Awareness of the thus detected predictable variability in the incidence of GD with frequencies lower than a year may be important in the diagnosis and treatment of this infectious disorder. PMID- 2217314 TI - Circadian periodicity of the time of onset of acute lower gastrointestinal bleeding. AB - We investigated the chronobiological parameters of acute gastrointestinal (GI) bleeding in 51 patients able to time-specify the onset of bleeding within 30 min of occurrence. Bleeding was determined to be either from the upper or lower GI tract. The upper GI bleeding group consisted of 32 patients (22 male, 10 female) who bled from peptic ulcer disease (16), Mallory-Weiss tear (4), gastritis (3), esophageal varices (3), gastric neoplasm (2), Dieulafoy's lesion (1), and unknown (3). The lower GI bleeding group consisted of 19 patients (9 male, 10 female) who bled from diverticulosis coli (5), hemorrhoids (2), arteriovenous malformations (2), colonic polyps (2), cecal ulcer (1), antibiotic-associated colitis (1), and unknown (6). Rhythmicity was evaluated by inferential statistics. The time of onset of lower GI bleeding (34 episodes) displayed significant circadian periodicity (p = 0.014) with its peak at 1100 h. Single cosinor analysis revealed: MESOR-1.42 (95% CI = 0.86- 1.97); amplitude = 1.22 (0.44-1.99); phase angle = -165.12 (-201.66 -128.58). Upper GI bleeding (42 episodes) displayed no circadian periodicity (p = 0.46). When both upper and lower GI bleeding were evaluated together, no circadian rhythm was evident (p = 0.07). We conclude that there is a circadian periodicity in the time of onset of only acute lower GI bleeding with its peak at 1100 h. The pacemaker of this periodicity remains unknown. PMID- 2217315 TI - Differential diurnal photosynthetic function in a psbA plastid gene chronomutant of Brassica napus. PMID- 2217316 TI - Temporal effects of pinealectomy, melatonin, and photocycle reversal on age related behavioral changes. PMID- 2217317 TI - Are tidal rhythms ultradian, circadian, or infradian? PMID- 2217318 TI - Blue light both synchronizes and inhibits growth of Schizosaccharomyces pombe at low temperatures. PMID- 2217319 TI - Chronobiologically deviant blood pressure in shift working police on metropolitan street duty. PMID- 2217320 TI - Chronobiological analysis of 1000 miles walked in 1000 hours. PMID- 2217322 TI - Is an eastbound circumpolar flight accompanied by phase advance of biological rhythms? AB - In the circumpolar region, the light-dark environment, which is the most potent Zeitgeber among others, and to which polar route travelers are exposed, varies greatly with the season and the time of day. Hence, resynchronization following an eastbound flight through this region will not necessarily be attained by phase advance of the biological rhythms. To prove this by simulation, a computer program was produced so as to locate the sun at any moment on any day and at any point on the earth. Rats were exposed to the changing pattern of light-dark condition which simulated flight schedules of polar, great circle and southern routes. Observation was made on the progress of biological resynchronization to the local time. The polar route simulation with an advance of 15 hours followed by a delay of the same hours resulted in phase delays on both trips. The great circle route simulation with a shift of 9 hours back and forth gave the same results. Another polar route simulation with an advance of 18 hours also resulted in a delay, while on their way back home some showed delay and some did advance. These findings suggest that the light-dark pattern after arrival works more rather than that during the trip, and that the resynchronization is apt to be achieved by delaying rather than by advancing, particularly when advancing of the phase by 6 hours or more is required. The critical limit seems to be subject to difference in species. PMID- 2217321 TI - Can athletic performance be statistically predicted? A follow-up study. PMID- 2217323 TI - Irregular work schedule: a case of a steward. PMID- 2217324 TI - Day-night patterns in workplace accidental deaths: role of alcohol abuse as a contributing factor. PMID- 2217325 TI - Circadian periodicity of performance in athletic students. PMID- 2217326 TI - Chronobiology of exercise: the influence of scheduling upon glycemic responses of control and of subjects with diabetes mellitus. AB - Exercise programs contribute significantly to: a) improve cardiovascular fitness; b) lower blood pressure in hypertension; and c) facilitate glycemic control in subjects with Diabetes Mellitus (DM). The mechanisms involved in promoting the above responses remain undetermined. Circadian phases at which exercise is applied could play a major role in optimizing the individual's physiological responses to exercise. In a pilot study, controls and a subject with Insulin Dependent Diabetes Mellitus (IDDM) were exercised at 0800 and 2000 hours: pedaling on an exercycle for 30 minutes at rates that maintained tachycardia at 70% of maximum reserve heart rates (Karvomen et al., 1957). All subjects were on "standard" rest-activity schedules (rest 2300-2400 to 0600-0700) and were allowed a single 360 ml Sustacal meal either at 2400 hours or at 1200 hours; i.e., 8 hours preceding the exercise program. Blood samples were obtained for determinations of glucose (finger tip) just before exercise (0 time) and at 10, 20, 30, 40 and 60 minutes of exercise/post exercise periods. The results suggest that non-diabetics experience a rapid decrease in blood glucose levels which does not recover during the 60 minute sampling time when exercise was in the morning. However, when these individuals exercised during the evening, glucose levels did not fall as much on a percentage basis and full recovery was obtained within 40 60 minutes. In the case of the diabetic patient, after morning exercise, glucose levels did not decline and after 40 minutes had risen above resting glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2217327 TI - Melatonin and phototherapy in premenstrual depression. PMID- 2217328 TI - Seasonal and circadian trends in occupational injuries. PMID- 2217329 TI - Influence of a rapidly rotating shift system on the fatigue of female workers. PMID- 2217330 TI - Digestive disturbances in shift-workers: a clinical statistical investigation. AB - In order to give a clarifying contribution about the probable relationship between shift-work and digestive diseases the authors have conducted a clinical and anamnestical investigation on digestive disturbances and alimentary habits of shift-workers comparing them with non shift-workers. The former group of subjects is engaged in very different activities conducted in variable working environments, with shift rhythms which are always disordered, sometime are imposed by the working Companies and sometimes chosen on the basis of personal necessities. The most interesting result of this study is represented by the confirmation of statistical significance among the larger incidence percentage of digestive disturbances between shift and non shift-workers. Moreover, statistical differences have been remarked among the different groups of shift-workers examinated. For these reasons the authors believe that shift-work is per se responsible of digestive diseases in the workers engaged to it and they also think that it is very important to distinguish the kind of shift work which may produce environmental, psychological and motivational differences. PMID- 2217332 TI - Recording of rhythms in organisms using video-digitizing. PMID- 2217331 TI - Toward a chronobiologic pacemaker. PMID- 2217333 TI - Day-night variations of normal number of computed tomography at several areas in human brain. PMID- 2217334 TI - Bounded limits and statistical inference in chronobiometry. PMID- 2217335 TI - Inferential sphygmochron to optimize the diagnosis and staging of arterial hypertension. PMID- 2217336 TI - Computing for clinical chronobiology, for bibliography compilation and for data storage, graphical presentation and statistical analysis. PMID- 2217338 TI - ChronoBioNet: global and local area networking in the chronobiological sciences. PMID- 2217337 TI - Meaning of the basic rest-activity cycle for psychohygiene. PMID- 2217340 TI - A mathematical model to explain the evolution of motor activity rhythm in rats. PMID- 2217339 TI - Chronobiologic blood pressure and heart rate assessment of patients with heart transplants. PMID- 2217341 TI - Caregiving merged with chronobiologic outcome assessment, research, and education in health maintenance organizations. PMID- 2217343 TI - Circadian rhythms of common laboratory profiles in serum and urine of healthy Indians. PMID- 2217342 TI - Circadian variations of blood and urinary constituents in renal stone formers. PMID- 2217344 TI - About-yearly pattern of cancer deaths, 1942-1987, in patients of a San Francisco hospital. PMID- 2217345 TI - Desynchronization of oral temperature and grip strengths: circadian rhythms in healthy subjects with irregular sleep-wake behavior. PMID- 2217346 TI - Genetic heterogeneity in control mechanisms of human reproduction: significance for isolation of patient subgroups. PMID- 2217347 TI - Chronobiological aspects of ischemic heart disease. PMID- 2217348 TI - Chronobiologic characteristics of ventricular ectopy in cardiac diseases. PMID- 2217350 TI - Diurnal variations of cardiac output in healthy young people. PMID- 2217349 TI - Longitudinal chronobiologic blood pressure monitoring for assessing the need and timing of antihypertensive treatment. AB - To examine the need for antihypertensive therapy and its timing, a 46 year-old woman with a 10-year history of "mild to moderate hypertension," treated for that span with 50 mg of hydrochlorothiazide per day, usually taken before retiring, carried out a study in a series of stages. Throughout the first 8 stages, she monitored her blood pressure and heart rate at 15-minute intervals around the clock for 70 consecutive days. In the first two stages, her medication was continued for a total of 10 days, of which the last 7 days constituted a double blind study start. For the next 25 days, she was placed on a placebo once in the evening. For the ensuing week, she received three tablets per day (in the morning, noon and evening), with all three being placebo. Thereafter, for consecutive 7-day spans, she was placed on treatment, only in the morning, only at noon or only in the evening, with placebo at other times. The desirability of one vs. another treatment was assessed by a comparison of slopes fitted to the daily MESORs; on that basis, the morning or noon treatment appeared to be possibly superior to the evening treatment. Eventually the patient was taken off medication; 5 months later her sphygmochrons, based on two-to-six day monitoring, were acceptable by current standards. The slope of MESORs may be a useful endpoint to assess the need for medication, to optimize its timing or to establish the likelihood that medication is not needed. This approach should, however, be based on several (rather than a single) double-blind alternation of drug and placebo treatments for spans that are the longer the smaller the extent of apparent blood pressure elevation. Thus, in the case of apparent mild MESOR hypertension, the blood pressure MESOR changes following the change in medication should be assessed during spans longer than one week. In the particular case studied, it seems possible that the patient had taken medication for 10 years, perhaps without justification. In cases of very mild blood pressure elevation, it seems desirable, by self-measurement or preferably automatic measurement, to take the patient off medication for spans measured in weeks or preferably months rather than days, in order to rule in or rule out the need for treatment, on the basis of repeated blood pressure profiles, to be compared eventually with reference standards from peers at low familial and personal risk of developing high blood pressure. PMID- 2217351 TI - Circadian sensitivity of soybean to a light activated herbicide. PMID- 2217352 TI - Chronobiological parameters as indicators of a disturbed organism-environmental relation in fish. PMID- 2217353 TI - Different best-fit multiples in lengths of incubation for altricial and precocial birds. PMID- 2217354 TI - Circadian variations in pigeon cropsac responses to prolactin determined at 3 hour intervals. PMID- 2217355 TI - Treatment of adolescent patients with sleep-wake schedule disturbances who complain of non-attendance at school. PMID- 2217356 TI - Circadian system in the insect testes controls the rhythmic release of sperm. PMID- 2217358 TI - Effect of photoperiod on development and fitness of a polymorphic leafhopper, Stirellus bicolor (Homoptera: Cicadellidae). PMID- 2217359 TI - Daily and seasonal flight activity of Tabanidae (Diptera) in the North Dakota sandhills. PMID- 2217360 TI - Evidence for ultradian rhythmicity in an intertidal crab. PMID- 2217357 TI - Circadian rhythm in the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae). PMID- 2217361 TI - Lighting schedule shifts prolong survival of enucleated Acetabularia. PMID- 2217362 TI - Circadian locomotor activity in an isolated cell of Paramecium. PMID- 2217363 TI - Differences in circannual characteristics of the incidences of amebiasis and giardiasis. AB - Entamoeba histolytica is the most common pathogenic intestinal parasite in Mexico. Prevalence rates of AM vary widely from place to place, being higher in areas with poor sanitation, households and institutions, and among male homosexuals. Early recognition and treatment may be necessary to prevent its spread in the community. Intervention by preventive health education is indicated. The timing of such educational endeavours may be adjusted to any rhythmic and to that extent predictable changes in the incidence of AM and of any other possibly related gastrointestinal parasitic disease, such as GD. Accordingly, monthly totals of cases of AM and GD detected in Monterrey, (Mexico) between November, 1985, and October, 1987, were fitted by linear least-squares with a 1-year cosine curve. The no-circannual rhythm assumption in the incidence of AM and GD was rejected in both cases (P = .006 and .049, respectively). A comparison of circannual parameters shows differences in M, A and phi between the incidences of AM and GD, the Ps for those comparisons being less than .001, .014 and .041, respectively. A high incidence of GD (above the yearly mean) consistently observed in April could be, however, related to the circannual pattern of AM, showing higher incidences in the spring. The timing of any preventive intervention should take into consideration the circannual variability in the incidence of AM and the differences or correlations with the circannual patterns of other gastrointestinal parasitic diseases. PMID- 2217364 TI - Is there a morning-evening difference in egg production of bloodworms, strongyle parasites of equines? AB - To test a claim that counts of the eggs of large strongyles or bloodworms, parasites of equines, are greater in morning fecal samples than in those from later in the day, and therefore, may be indicators of circadian variations in these worms, samples from one pony and nine horses were analyzed for strongyle eggs. Samples were collected twice per day, about 7:30 and again about 19:30, during two, 24-day periods. Individual counts varied from 0 to 1184. The mean of all 7:30 counts was 212.52; that of 19:30 counts was 236.03. The difference is not significant, and does not support the idea of circadian differences in egg production of these nematodes. PMID- 2217365 TI - Rat testicular growth and an infradian behavioral cycle of anxiety. PMID- 2217366 TI - Circadian and ultradian rhythms in ruminants: relevance to farming and science. PMID- 2217367 TI - Paleochronobiology circadian rhythms, gauges of adaptive Darwinian evolution; about 7-day (circaseptan) rhythms, gauges of integrative internal evolution. PMID- 2217368 TI - Oviposition rhythms in Biomphalaria spp. (Mollusca: Gastropoda). 1. Studies in B. glabrata, B. straminea and B. tenagophila under outdoor conditions. PMID- 2217369 TI - Oviposition rhythms in Biomphalaria spp. (Mollusca: Gastropoda). 2. Comparative studies in B. glabrata under natural and artificial light cycles. PMID- 2217370 TI - Biological oscillations and agriculture: a brief introduction. PMID- 2217371 TI - Covariance of daylight, sport participation and sleep patterns. PMID- 2217372 TI - Chronobiology and agroecosystems. AB - Influences of seasonal changes on the circadian system were observed in studies of feeding activity in four species of ducks and of feeding and locomotor activity in two species of mammals kept in captivity in the natural LD cycle. Feeding and locomotor oscillators had different sensitivities to exogenous synchronizers. Changes from a circadian to an ultradian feeding rhythm occurred as a result of courtship and breeding behavior in two duck species. Different phases of feeding rhythms in ducks were shown to have important ecological consequences for establishing the species in appropriate time niches in agricultural wetlands. Detailed study of annual, seasonal and daily rhythms of feeding and locomotion measured simultaneously in captivity and in free-ranging animals is necessary to elucidate the structure and function of food chains and webs. Activity rhythms of both producers and consumers (predators and prey) during daily and annual cycles is of special concern. This contribution of chronobiology will further our understanding of the niche of selected species in agricultural ecosystems. PMID- 2217373 TI - Effects of biological and environmental factors on activity rhythms of wild animals. AB - This paper reviews information on the effects of biological and environmental factors on activity rhythms of wild animals monitored by radio telemetry. Variations in radio signals received from free-ranging animals are used to determine the pattern of activity and rest. Telemetry is especially effective for obtaining activity data from wild animals at night and from those living in dense vegetation or underground. Biological factors such as breeding behavior, care of young, time of last eating, and food storage cause changes in daily activity patterns. Similarly, environmental factors such as temperature, snow cover, food supply and disturbance caused by humans in an urban setting also cause changes in daily activity patterns. The observed modifications of activity rhythms show that controlling mechanisms allow wild animals to quickly respond to changing biological and environmental factors. PMID- 2217374 TI - Oscillations in plant metabolism. PMID- 2217375 TI - Growth rhythms in higher plants. PMID- 2217376 TI - Photoperiodic and thermoperiodic regulation of assimilate partitioning into storage carbohydrates (starch and sugar) in leaves of crop plants. PMID- 2217377 TI - Modified behavior oscillations in diseased plants and its implication to epidemiology and crop loss assessment. PMID- 2217378 TI - Phase response curve evoked by fusaric acid and pulses of light and darkness on the circadian leaf movement rhythm of the cotton plant. PMID- 2217379 TI - A self-assessment questionnaire for the determination of morningness-eveningness types in Brazil. PMID- 2217380 TI - Rhythmic responses to hormones and herbicides in plants. PMID- 2217381 TI - Chronobiology and aquaculture: neglected opportunities. PMID- 2217382 TI - Relation of mesor to circadian amplitude as a criterion of mental load. PMID- 2217383 TI - Mutagens and carcinogens in food. PMID- 2217385 TI - Aberrant crypt foci in the detection of colon carcinogens. PMID- 2217384 TI - Polycyclic aromatic hydrocarbon carcinogens. PMID- 2217387 TI - Genotoxic mechanisms of fecapentaene-12 in human cells. AB - Fecapentaenes are mutagenic to both bacterial and human cells and can morphologically transform murine Balb/c 3T3 cells. DNA damage induced by fecapentaene-12 includes DNA cross-links, DNA protein cross-links and single strand breaks. Oxy- and alkyl-radicals have been detected in aqueous solution using spin traps coupled with EPR. Oxy-radicals thus formed can then directly damage DNA to form DNA SSB's or 80HdG. Radiolabeling studies suggest that fecapentaene-12 may also form specific adducts either directly or after aldehyde formation. Hence fecapentaene-12 may cause DNA damage by two distinct mechanisms i.e., directly (alkylation) or indirectly (via free radicals). Reactions of fecapentaene-12 with GSH tend to support this hypothesis. Possible synergistic interactive effects of DNA damage caused by direct and indirect mechanisms are currently under investigation. PMID- 2217386 TI - Dietary factors affecting spontaneous chromosomal damage in man. AB - The data summarized above demonstrate that dietary and nutritional factors can influence spontaneous rates of chromosomal damage in laboratory animals, and suggest strongly that certain of these dietary factors may exert a quantitatively significant influence on spontaneous chromosomal damage frequencies in human populations. Among a total of 77 splenectomized human subjects examined in two separate studies, consumption of caffeinated beverages, mild folate deficiency, and consumption of calcium supplements by older women were statistically associated with higher frequencies of micronucleated cells. Subjects who reported taking dietary supplements of vitamins C, E, or A had significantly lower values. Age was strongly associated with micronucleus frequency when other factors were not considered, but was only weakly associated when all factors were included in a multiple regression analysis. Followup studies in laboratory animals established that caffeine is a strong inducer of micronuclei in marginally folate deficient mice, but not in folate-sufficient mice. Deficiencies of magnesium or zinc, two metals required for DNA synthesis and/or maintenance of chromatin structure, increase the rate of spontaneous chromosomal damage in laboratory animals. These and other data discussed above suggest that dietary deficiencies of nutrients required for nucleotide synthesis, such as folate, vitamin B12, and magnesium, may increase spontaneous chromosomal damage, and may strongly influence the genotoxic response to other dietary factors. It is critically important to systematically investigate the quantitative importance of the above factors in man, using 1) human cross-sectional epidemiology and supporting animal data to identify potentially significant risk factors and to elucidate the mechanisms of interaction among these factors, and 2) controlled intervention studies in man to determine the quantitative significance of these factors in human populations. We feel the use of splenectomized populations, in which chromosomal damage is easily monitored and in which the marker of damage is temporally responsive to removal of risk factors, will play an important role in the intervention phase of such studies. PMID- 2217388 TI - Metabolic activation of food hepatocarcinogens in hepatitis B virus-infected humans and animals. PMID- 2217390 TI - New mutagens from cooked food. PMID- 2217391 TI - Antimutagenic/anticarcinogenic food components. PMID- 2217389 TI - Mechanisms of oxidant carcinogenesis. PMID- 2217392 TI - Conjugated dienoic derivatives of linoleic acid: mechanism of anticarcinogenic effect. PMID- 2217393 TI - Antimutagenic heat stable antioxidants. PMID- 2217394 TI - Soybeans inhibit mammary tumors in models of breast cancer. PMID- 2217395 TI - Chemoprevention and chemotherapy of mammary tumors by monoterpenoids. PMID- 2217397 TI - Diet and cancer: regulatory perspectives in Europe. PMID- 2217396 TI - Opportunities for nutritional scientists in cancer prevention. PMID- 2217398 TI - Mutagens and carcinogens in the diet. Regulatory perspective: Japan. PMID- 2217399 TI - Regulation of carcinogens and mutagens in foods in the United States. PMID- 2217400 TI - Mutagens and carcinogens in the diet: summary and perspectives. PMID- 2217401 TI - Metabolism and biodisposition of heterocyclic amines. AB - The metabolic pathways of activation and detoxification of heterocyclic aromatic amines are similar to those reported for other aromatic amines. In vitro studies have shown that oxidation of the exocyclic amine group by cytochrome P450 results in formation of the mutagenic N-hydroxylamine derivatives. However, metastable conjugates of the hydroxyamino metabolites have not been identified in biological fluids such as bile or urine of rodents. This is in contrast to the aromatic amines 2-acetylaminofluorene and 4-aminobiphenyl in which both the hydroxamic acid and the N-glucuronide of the hydroxylamine have been identified (Miller et al., 1960; Radomski et al., 1973). This suggests that either very low levels of the N-hydroxyamino metabolites of heterocyclic amines are formed or that they are not stable and react rapidly. Phase II conjugation reactions include N glucuronidation and the unusual pathway of sulfamate formation for several of these amines including IQ and MeIQx. Conjugation to glutathione has not been reported to be a major route of in vivo metabolism and detoxification of heterocyclic amines. Studies conducted in vitro are few and inconclusive. One study has shown that glutathione may serve both to activate as well as to detoxify hydroxyamino-Trp-P-2 (Saito et al., 1983). While a second study demonstrated that depletion of cellular glutathione increased the binding of Trp P-2 metabolites to DNA in hepatocytes (Mita et al., 1982). Thus the role that glutathione plays in protecting the cell against this class of genotoxins merits further investigation. Much data has been gathered on human exposure to heterocyclic amines and mechanisms of genotoxicity have been elucidated, however, risk estimation of cancer development in humans by these carcinogens is still uncertain. There may be differences between man and rodents in the absorption, metabolism and activation versus detoxification as well as rates of excretion of heterocyclic amines. Humans also are exposed to many other carcinogens and potential tumor promoters (Sugimura, and Sato, 1983). Tumor promoters may enhance the effects of carcinogens. Fortunately, there also are tumor inhibiting factors in the diet which may weaken the biological activity of carcinogens (Wattenberg, 1985). Such variables make it difficult to extrapolate carcinogenicity data from animal experiments to assess risk to human cancer development.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2217402 TI - Preferential activation and genotoxicity of food derived heterocyclic amine mutagens by recombinant cytochrome P4501A2. PMID- 2217403 TI - Mutagens from model systems. PMID- 2217405 TI - Chemotherapy for invasive bladder tumors. AB - The presently reported phase II trials are not comparable but do provide leads. The need for chemotherapy is based on the original urologic assessment. Those patients requiring radical surgery can be considered, but the aim of therapy must be defined. For those with minimally advanced (T2, T3a) disease, bladder preservation is possible. For those with higher stage tumors, therapy is directed more for the treatment of micrometastases, with bladder preservation as a secondary goal. While bladder preservation is possible in selected cases, chemotherapy does not eliminate the need for definitive local therapy. The more widespread adaptation of ileo neo-bladders may eliminate the reluctance of some patients and physicians to proceed with definitive therapy. However, it must be emphasized that neo-bladders alone will not alter the natural history of this disease, but may improve quality of life. The results from advanced disease studies clearly show that selected patients can achieve long term survival using chemotherapy alone. These data make survival a valid endpoint for clinical trials recognizing the large number of patients required and that progress in cancer generally comes in comes in small steps. However, more effective systemic therapy is required before a significant impact on the natural history of invasive bladder cancer can be realized. For these reasons, neo-adjuvant chemotherapy must be considered investigational and physicians are urged - despite their reluctance to enter patients on clinical trials. PMID- 2217404 TI - Carcinogenicity of mutagens from cooked meats. PMID- 2217407 TI - Southwest Oncology Group Study 8710: trial of cystectomy alone versus neo adjuvant M-VAC and cystectomy in patients with locally advanced bladder cancer (Intergroup Trial 0080). PMID- 2217406 TI - Randomised intercontinental trial of locoregional therapy with or without neoadjuvant chemotherapy. PMID- 2217408 TI - Neoadjuvant chemotherapy in invasive bladder cancer. Trial design. PMID- 2217409 TI - Extended experience of neo-adjuvant M-VAC chemotherapy for T1-4 N0 M0 transitional cell carcinoma of the urinary bladder. PMID- 2217410 TI - Neoadjuvant medium-dose methotrexate, cisplatin in category T3b-T4a (N0M0) bladder cancer. AB - Between July 1985 and December 1988, 31 consecutive patients with category T3b T4a (NOMO) urothelial cancer of the urinary bladder were entered into a phase II study of neoadjuvant chemotherapy with medium-dose methotrexate (300 mg/m2 followed by folinic acid rescue), cisplatin (100 mg/m2 continuous i.v. infusion) every 4 weeks for a total of 4 courses. Six patients did not respond to the first two courses of neoadjuvant chemotherapy and another 3 were considered non responders after 4 courses. Three of these 9 patients progressed and could not undergo salvage cystectomy. Only 4 patients (13%) entered complete remission, and one of them refused surgery. All the 18 (58%) partial responders underwent radical cystectomy. The overall 2-year disease-free survival is 72%: it is 100% for the 4 complete responders, 76% for the 18 partial responders and 56% for the 9 nonresponders. A longer follow-up is necessary to evaluate the impact of the neoadjuvant chemotherapy on survival of category T3b-T4a (NOMO) bladder cancer. PMID- 2217411 TI - Phase II trial of pre- and postoperative cisplatin, methotrexate and vinblastine in infiltrating bladder cancer: a three year experience. PMID- 2217412 TI - Neo-adjuvant M-VAC (methotrexate, vinblastine, adriamycin, and cisplatin) for infiltrating bladder cancer: initial results in Italy. PMID- 2217413 TI - Neo-adjuvant intra-arterial chemotherapy in locally advanced bladder cancer. PMID- 2217414 TI - Radical TUR and chemotherapy aiming at bladder preservation. PMID- 2217415 TI - Neoadjuvant M-VAC chemotherapy and partial cystectomy for treatment of locally invasive transitional cell carcinoma of the bladder. PMID- 2217416 TI - Bladder sparing approach to muscle invasive carcinoma of the bladder. PMID- 2217418 TI - Evaluation of tumor response and prognostic factors in patients with bladder cancer undergoing combined radiotherapy and chemotherapy. PMID- 2217420 TI - Sensitivity to short-term chemotherapy in patients with bladder cancer evaluated by computed tomography of the primary tumor. PMID- 2217419 TI - Combination chemotherapy followed by surgery: the case for a marker lesion. PMID- 2217417 TI - M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) and bladder preservation. PMID- 2217421 TI - EORTC Group Study 30851: a phase II study of neoadjuvant chemotherapy in patients with invasive bladder cancer. PMID- 2217422 TI - The prognostic value of the pT-category after combination chemotherapy for patients with invasive bladder cancer who underwent cystectomy. EORTC-GU group. PMID- 2217423 TI - Criteria of response to neo-adjuvant chemotherapy in the treatment of invasive bladder cancer: a critical assessment. AB - In this paper, we have addressed the difficulties of the assessment of response in clinical trials of pre-emptive or neo-adjuvant chemotherapy for bladder cancer. We have attempted to set guidelines that can be applied to this problem. It is clear that, in order for real progress to be made in this field, considerable attention must be paid to the design of the appropriate trials, and that innovations must be tested against standard treatments. To date, many phase II or pilot studies have been effected and reported, but without a clear determination of a resulting survival benefit compared to standard treatment. Although we have discussed the assessment of response in this paper, it should not be forgotten that there is no consensus that response is a useful endpoint in this setting. In the randomized assessment of the role of pre-emptive intravenous Cisplatin plus radiotherapy versus radiotherapy alone for invasive bladder cancer, carried out by the West Midlands and Australian Bladder Cancer Study Groups, response was not regarded as an important endpoint, and the trial assessed survival as the most important index, with documentation of toxicity as a secondary goal (Raghavan, 1989). Future phase III trials should address survival as the primary endpoint. PMID- 2217424 TI - The role of radiotherapy in the treatment of muscle invasive bladder cancer. AB - The treatment of muscle invasive bladder cancer still remains controversial. It is becoming more clear, however, that attempts to retain the functional capacity of the urinary bladder by the use of non-surgical methods may be of benefit in the long-term. Studies using radiotherapy in combination with chemotherapeutic agents or intravesicle sensitizers, or the use of radiotherapy alone, but optimized (i.e., brachytherapy and altered fractionation) may be able to achieve improved local control whilst retaining a functional bladder. Attempts to couple this with improved survival due to the sterilization of occult metastases is still subject to much debate. PMID- 2217425 TI - The role of surgery in initial staging and follow up. PMID- 2217426 TI - Pathology of bladder cancer: assessment of the primary lesion and response to therapy. PMID- 2217427 TI - Neoadjuvant chemotherapy in invasive bladder cancer. Trial design and statistics. PMID- 2217428 TI - Endpoints of clinical trials for muscle-invasive bladder cancer. PMID- 2217430 TI - The integration of chemotherapy, radiotherapy and transurethral surgery in bladder-sparing approaches for patients with invasive tumors. PMID- 2217429 TI - The NCI-Canada trial of concurrent cisplatin and radiotherapy for muscle invasive bladder cancer. PMID- 2217431 TI - Neo-adjuvant cisplatinum in locally advanced urothelial bladder cancer: a prospective randomized study of the group CUETO. PMID- 2217432 TI - An overview of megakaryocytopoiesis. PMID- 2217433 TI - Use of in situ hybridization to study human megakaryocyte gene expression. PMID- 2217435 TI - The regulatory control of hemopoietic populations. AB - The identification and mass-production by recombinant technology of twelve of the regulatory glycoproteins controlling hemopoiesis has represented a major advance in understanding hemopoiesis and introduces the possibility of being able to correct major disease states involving hemopoietic cells. Information so far on the control of megakaryocyte formation indicates that this follows the general pattern operating for other hemopoietic subpopulations and the present conference will review the new knowledge of specific factors influencing megakaryocyte formation and function. PMID- 2217434 TI - Megakaryocytopoiesis in man and laboratory animals. Conclusions derived from comparative studies and recently discovered animal models with megakaryocyte anomalies. PMID- 2217436 TI - Studies on paracrine regulation of murine megakaryocytopoiesis. PMID- 2217437 TI - Regulation of in vitro human megakaryocyte maturation. PMID- 2217438 TI - Regulation of human megakaryocytopoiesis by interacting cytokines. PMID- 2217439 TI - Role of thrombopoietin in controlling blood platelet production. PMID- 2217440 TI - Control and implications of polyploidization in human megakaryocytes. PMID- 2217441 TI - Platelets contain several inhibitors of megakaryocyte growth and ploidization. PMID- 2217442 TI - Delivery of platelets from megakaryocytes. PMID- 2217443 TI - Growth and differentiation of two human megakaryoblastic cell lines; CMK and UT 7. AB - We showed that these two cell lines obviously expressed megakaryocytic phenotypes, such as multilobular, hyperploid nuclei, expression of GPIIb/IIIa complex, GPIb and PPO, although they have been originated from patients with leukemia. Furthermore, these cells had following characteristics. First, they responded to various kinds of hemopoietic factors. Especially, UT-7 cells were solely dependent on GM-CSF, IL-3 or Ep. Therefore UT-7 cells are useful to the assay of these factors as megakaryocytic cells. These facts provide us with new questions: why they are dependent on plural number of factors? How are the expressions of their receptors controlled. Is there an "autocrine" mechanism controlling their growth? Among these questions, we have just started with the Ep receptors, and most of the problems remain to be clarified. Second, PMA treatment suppressed their growth, but enhanced their differentiation and maturation. Among the megakaryocytic phenotypes, increase in GPIIb/IIIa complex, determined by a biochemical method, PPO by ultrastructural study, and the increase in cellular ploidy were clearly observed by PMA treatment. The phorbol ester PMA is well known to induce the differentiation of various kinds of leukemic cells (Rovera et al., 1979). Detailed molecular basis to clarify why the same PMA treatment causes differentiation into different cell lineages, dependent on cellular origin of the target cells, should be further studies. Third, the cells produced hemopoietic growth factors by PMA treatment, the majority of which was GM-CSF. Humoral control of megakaryopoiesis still remains unsettled. Our study may shed a light on its "multistep" regulatory mechanisms. Availability of a large amount of homogeneous megakaryocytic populations, which are responsive to hemopoietic factors and phorbol ester, will provide us with a great deal of informations concerning the molecular insight of megakaryocytopoiesis and thrombocytopoiesis. PMID- 2217444 TI - Retroviral antigen expression on megakaryocytes and platelets: possible implications in the pathogenesis of thrombocytopenia. PMID- 2217445 TI - Analysis of c-sis/PDGF-B mRNA expression in megakaryocytic cells of patients with myeloproliferative disorders. PMID- 2217447 TI - Megakaryocytes and thrombopoiesis in vascular disease. PMID- 2217446 TI - Flow cytometric analysis of megakaryocytes (Mks) from patients with platelet disorders. PMID- 2217448 TI - Inherited disorders of platelets and megakaryocytes. PMID- 2217449 TI - Circulating megakaryocytes and platelet production in the lungs. PMID- 2217450 TI - Platelet GPIIb as a marker for megakaryocytopoiesis. PMID- 2217451 TI - Molecular biology of the megakaryocyte-specific gene platelet factor 4. PMID- 2217452 TI - Molecular biology of human platelet membrane glycoprotein Ib. PMID- 2217453 TI - Proteoglycans in megakaryocyte development. PMID- 2217454 TI - The diagnosis and management of localized prostate cancer. PMID- 2217455 TI - Peptide growth factors: a new frontier in prostate cancer. PMID- 2217456 TI - Retinoic acid and prostatic cancer cell growth. PMID- 2217457 TI - Morbidity of modified pelvic lymphadenectomy and external beam radiation therapy for prostatic cancer. PMID- 2217458 TI - History and physical examination in prostate cancer. Which information is essential in diagnosis and follow-up? PMID- 2217459 TI - Biopsy techniques and cytology in prostate cancer. PMID- 2217460 TI - Staging of the primary. PMID- 2217461 TI - Lymph node staging of potentially curable prostatic carcinoma. PMID- 2217462 TI - The staging of M+ disease. AB - Patients with newly diagnosed prostatic cancer should be investigated with regard to the presence or absence of distant metastases by: (1) Clinical history especially of weight loss, recent pain, or analgesics intake. (2) Physical examination, looking especially for hepatic enlargement, peripheral lymph nodes, local bone tenderness. (3) Performance status. (4) Hemoglobin, creatinine, PSA and/or PAP, alkaline phosphatases, liver tests, testosterone. (5) Bone scan with X-ray of doubtful hot spots. (6) Chest X-ray. (7) Ultrasound scans (liver, kidney, lymph nodes) or CT scan may be indicated if abnormal blood parameters or in specific situations. (8) Other investigations are only indicated in special circumstances. Follow-up should include: (1), (2), (3), (4) every 3 months. For patients in clinical trials, depending on the end point, bone scan should be repeated every 6 months or possibly depending on the prognostic group (good: every 12 months; bad: 3 to 6 months). For routine clinical management, it could be repeated only when markers (PAP, PSA, alkaline phosphatase) show significant (25-50%) increase and provided the result will influence treatment. Other investigations should only be repeated or performed if abnormal at the start of if clinical data require them. PMID- 2217463 TI - Objective response criteria in prostate cancer. PMID- 2217464 TI - Assessment of quality of life and subjective response criteria in patients with prostatic cancer. PMID- 2217466 TI - Progress and controversies in the management of seminoma. AB - A series of controversies in the management of testicular seminoma were raised in this paper. Some of these issues have been discussed in more detail while others such as the optimal dose of radiation in stage II disease, and the management of residual masses post-chemotherapy are discussed in the consensus statement generated from the conference. It is important to consider these controversies in the context of the excellent outcome of current therapy. It is extremely unusual in the management of neoplastic disease to be attempting to refine therapy when the expected cure rate is 97% as it is in seminoma. It is only when our understanding of the disease process is so good, and our treatments so effective, that we can afford to direct investigative effort to minimizing the morbidity of our therapies. PMID- 2217465 TI - Time-dependent prognostic factors in advanced prostatic cancer. PMID- 2217467 TI - The role of lymph node dissection in testicular cancer. PMID- 2217468 TI - Testis cancer. Aggressive therapy for advanced disease. PMID- 2217469 TI - Aetiology and epidemiology of testicular cancer: report of consensus group. PMID- 2217470 TI - Basic principles of clinical trials as applied to testicular cancer. PMID- 2217471 TI - Consensus on pathological classifications of testicular tumours. PMID- 2217472 TI - Consensus statement on the investigation and management of testicular seminoma 1989. AB - In the past 10 years, many developments have allowed us to understand more fully the natural history and routes of spread of testicular seminoma. The development of radiological tests such as CT scanning has allowed us to better assess the extent of disease. The availability of serum tumor markers AFP and beta HCG has facilitated the recognition of the presence of occult non-seminomatous elements. These developments plus the knowledge that seminoma is sensitive to cisplatin containing chemotherapy and that it is exquisitely sensitivity to radiation therapy resulted in further improvement in therapy. Overall we now expect 97 to 98% of patients will be cured of their disease. Currently, a number of issues in the management of seminoma remain controversial. These controversies however impact on very small proportion of patients with seminoma. Between 5 and 10% of patients have stage IID, III, or IV disease and 10 to 20% of these patients ie: 1 or 2% of the total population actually die from testicular seminoma. Thus it is for patients with advanced disease that we seek to define the nature of optimal chemotherapy, that is the most effective yet least toxic regimen. For those 1 or 2% of patients dying of seminoma we seek to identify prognostic factors to identify these patients and better treatments for them. Refinements in the application of radiation therapy for early stage disease, should allow some reduction in the morbidity of radiation without compromising control rates. Testicular seminoma its investigation and management, serves as a model for understanding other malignant processes and for orderly ways in which to refine the therapeutic ratio in the management of disease. PMID- 2217473 TI - Second line treatment of hormone refractory prostatic cancer patients. PMID- 2217474 TI - Surgery in advanced disease for testicular cancer. PMID- 2217475 TI - Long-term side effects after treatment of testicular cancer. PMID- 2217476 TI - The management of end-stage carcinoma of the prostate: philosophy and fact. PMID- 2217477 TI - What is new in endocrine therapy of prostatic cancer? PMID- 2217478 TI - The value of the bone scan. PMID- 2217479 TI - Prognostic factor analysis from EORTC trials in advanced prostatic cancer. EORTC GU Group. PMID- 2217480 TI - Scientific background of hormonal treatment of prostate cancer. PMID- 2217481 TI - EORTC Genitourinary Group: prostate cancer studies. PMID- 2217482 TI - M.R.C. trials in prostate cancer. PMID- 2217483 TI - Response criteria in research protocols for prostatic cancer. AB - This paper highlights some problems in the application of different response criteria for prostatic cancer and discusses what the most practical response criteria is. In this paper, we present some results of a multi-institution collaborative clinical study which employed response criteria developed by a Japanese study group (the Japanese Response Criteria for Prostatic Cancer; JRCPC) are reported. The JRCPC assesses response of a number of foci of disease independently, i.e., primary prostatic lesion, bone metastatic lesions and serum PAP level as well as bidimensionally measurable lesions. The overall response is evaluated on the basis of the response for each of the above parameters. In the present study, the serum PAP level was found to be, at present, the most sensitive parameter for predicting survival of patients with prostatic cancer. If the response is evaluated and recorded as a function of each parameter, as in the case of the JRCPC, it is relatively easy to re-evaluate the results using other criteria, thereby making it possible to compare the results with the results of other studies which employ different criteria. In the future, it will be important to improve the accuracy of measurement of the response of a variety of parameters specific for prostatic cancer in order to establish reliable response criteria to evaluate therapy. PMID- 2217484 TI - Oncogene expression in prostate cancer. AB - Molecular biology has proven to be instrumental in studies on the onset and progression of cancer. Reasoning that tumorigenesis can be considered as a multistep process in which a normal cell gradually escapes from its delicately regulated growth pattern, one might describe this process in terms of gene expression. The group of genes that are good candidates for investigation in this context are the proto-oncogenes. Recent progress in oncogene research, has led us to believe that the group of oncogenes is much greater in number than the fifty so far characterized, since all growth factor-, growth factor receptor-, signal transducer- and transcription regulating genes have a potency to become oncogenic. Recessive genes, such as tumor suppressor genes might be equally relevant to the onset and progression of cancer. In this paper we confine ourselves to the role of protooncogenes in urological cancers, in particular prostate cancer. The usefulness of these genes as markers of progression in prostate cancer will be discussed. PMID- 2217485 TI - The peritoneum and its response to surgical injury. PMID- 2217486 TI - Can a pro-coagulant substance prevent adhesions? PMID- 2217488 TI - Staging of adnexal adhesions: a brief history. AB - Arriving at a system for staging adnexal disease is a scientific, clinical and political process which has already begun. Gynecologic oncologists started this process in 1967, and are still arriving at refinements and adjustments in the staging of cancer after 22 years. To rigorously evaluate new medical and surgical technologies in the treatment of adhesions it is important for infertility surgeons to continue the process of working towards a classification system, keeping in mind that it will take a long time. PMID- 2217487 TI - Nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of postsurgical adhesion. PMID- 2217489 TI - Interceed (TC7) as an adjuvant for adhesion reduction: animal studies. PMID- 2217490 TI - Alternative reproductive technologies vs. adhesiolysis. PMID- 2217491 TI - Adhesion formation/reformation. PMID- 2217493 TI - Preventing adhesions--electrosurgery: advantages and disadvantages. AB - Though electrosurgery has been with us for decades, few surgeons have received formal training in its potential uses. The erroneous belief that electrosurgery techniques increase scar formation or impair healing processes, has led surgeons to other methods to deliver energy to the living cell. At the cellular level, a watt, is a watt, is a watt -- knowing how to calculate and administer that energy is the challenge. Laser technology has forced the bioelectrical engineers to develop 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 current flow meter for bipolar forceps will now tell the surgeon when all of the tissue has been desiccated. Soon I hope the power density and wattage delivered at the electrode tip will be easily displayed for the biogynecologic surgeons. Who knows, one day we may have a "laser-electrode" system to meet all of our needs. PMID- 2217492 TI - Microsurgical adhesiolysis. PMID- 2217494 TI - Laser surgery and adhesion formation. PMID- 2217495 TI - Gore-Tex surgical membrane. PMID- 2217496 TI - Impaired hoarding and olfactory learning in DSP-4-treated rats and control cagemates. AB - The possibility that variables affecting rats' home-cage odor preferences also influence hoarding behavior was examined. Neonatal male rats were injected SC with the noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), or with vehicle. At weaning, rats were assigned to control-only, DSP-4 only, or mixed groups of DSP-4 and control rats. For the next 10 days, half the rats in each social condition were housed in cedar shavings, and remaining rats were housed in pine. Exposure to cedar significantly increased preference for the odor in control-only groups, but not in DSP-4-only or mixed treatment groups. Control-only groups also hoarded significantly more pellets per animal than rats in the other two social conditions. The results suggest that both olfactory adaptation and hoarding can be impaired by either neonatal NE depletion or an abnormal social environment. PMID- 2217497 TI - Initiation and execution of locomotion elicited by diencephalic stimulation: regional differences in response to nembutal. AB - At moderate levels of Nembutal, within the anesthetic range, locomotor stepping can be elicited by brain stimulation. We determined if Nembutal (7, 14 and 28 mg/kg) had different effects on locomotion elicited by stimulation at different brain regions. Two regions were compared: the medial forebrain bundle (MFB, 13 sites) and the areas medial and dorsal to it (MED/DORSAL, 20 sites). Locomotion was produced by electrical stimulation (50 microA, 0.5 msec pulses, 10 to 160 Hz) of unrestrained rats in a rotary runway. The latency to initiate locomotion and the time to complete 1 revolution of the rotary were measured. With no drug, MFB locomotion was initiated sooner but took longer to complete than MED/DORSAL locomotion. Nembutal at 7 mg/kg did not affect initiation of MFB or MED/DORSAL locomotion. Nembutal at 14 mg/kg shortened MFB initiations, but this dose prolonged MED/DORSAL initiations. Initiations with both types of sites were blocked with 28 mg/kg. The 7 and 14 mg/kg doses prolonged the locomotor completion times of the MFB sites but not of the MED/DORSAL sites. The results indicate that the response to Nembutal differs qualitatively for locomotion elicited by stimulation of the MFB and locomotion elicited by stimulation of the medial and dorsal hypothalamus. The mechanisms underlying the difference remain to be elucidated; they may relate to nonlocomotor behaviors also elicited by stimulation or to the motivational states reflected in those behaviors. PMID- 2217498 TI - Latency to initiate locomotion elicited by stimulation of the diencephalon positively correlates in awake and anesthetized rats. AB - Locomotor stepping can be elicited by brain stimulation at various diencephalic sites under moderate levels of Nembutal. This study determined if locomotor initiation measured under anesthesia provides a valid measure of the intersite factors which determine initiation in the awake condition. We compared the latencies to initiate locomotor stepping elicited by electrical stimulation (50 microA, 0.5-msec pulses, 10 to 160 Hz) by rats tested while awake and unrestrained in a rotary runway or anesthetized and held in a stereotaxic apparatus. In the latter tests, initial anesthesia was provided by Nembutal (25 mg/kg) and 2% halothane and maintenance anesthesia was provided by 7 mg/kg as needed and local injections of lidocaine. For 30 sites in 16 rats, average locomotor initiation latency in the awake condition and the shortest latencies in the anesthetized condition were positively correlated (r = .78). Locomotion at sites with long latencies in the awake condition was frequently blocked in the anesthetized condition, but sites with short latencies were rarely blocked. The results indicate that the shortest locomotor latencies in the anesthetized condition approximate the latencies measured in the awake condition. It is concluded that the anesthetized condition can provide valid initiation measures, but sites with long latencies in the awake condition are prone to depression under anesthesia. PMID- 2217499 TI - Criterion for learned helplessness in the rat: a redefinition. AB - Numerous investigators have reported difficulty obtaining reliable learned helplessness. Various laboratories have used differing test environments and criteria, making comparisons among experiments difficult. Some use an escape deficit criterion, in which escape is slowed down in a shuttle box, while others have used an escape failure criterion, in which rats do not escape at all on most test trials. Little work has been done to test the validity of LH, i.e., the prediction of persistence of escape failure after exposure to uncontrollable shock. The present studies demonstrate that the reliability and validity of learned helplessness can be improved by 1) modifying the shuttle box to increase task difficulty and decrease random escape behavior and 2) adopting a new escape failure criterion for helpless behavior which is based on statistical prediction of the persistence of escape deficits. PMID- 2217500 TI - Antagonism of cocaine, amphetamine, and methamphetamine toxicity. AB - The effect of diazepam, haloperidol, MK-801, and propranolol in antagonizing behavioral symptoms induced by lethal doses of cocaine, amphetamine, and methamphetamine were studied in a rat model. Animals were first pretreated IP with potential antagonists, diazepam (2, 5, and 10 mg/kg), haloperidol (5, 10, and 20 mg/kg), propranolol (5, 10, and 20 mg/kg), MK-801 (0.5, 1.0, and 2.5 mg/kg), and then were challenged IP with cocaine (70 mg/kg) (LD85), d-amphetamine (75 mg/kg) (LD100), and methamphetamine (100 mg/kg) (LD90). Diazepam, at all doses, provided significant protection against cocaine- (p less than or equal to 0.01) and methamphetamine- (p less than or equal to 0.05) induced seizures and produced a dose-dependent effect against amphetamine-induced seizures. MK-801, at all doses, reduced seizures in all groups (p less than or equal to 0.01). Propranolol altered the incidence of methamphetamine-induced seizures. Significant protection against cocaine-induced death was afforded by diazepam (p less than or equal to 0.01) and propranolol (p less than or equal to 0.05). Significant protection against amphetamine-induced death was provided by haloperidol (all doses, p less than or equal to 0.1), MK-801 (all doses, p less than or equal to 0.1), and propranolol (10 and 20 mg/kg, p less than or equal to 0.1). No agent reduced the incidence of methamphetamine- (50 or 100 mg/kg) induced death. The failure of d-amphetamine antagonists to protect against methamphetamine-induced toxicity and death suggest that different mechanisms of toxicity may exist between these drugs. PMID- 2217502 TI - Associative influences on tolerance to decreased fixed-interval responding by clonidine. AB - Responding of rats was maintained under a 5-min fixed-interval schedule of food presentation. One group of animals (n = 5) received the alpha-2-agonist clonidine (0.1 mg/kg/day) before experimental sessions for 16 weeks. Additional animals (n = 5) also received 0.1 mg/kg/day for 16 weeks but experienced drug administration after sessions for 4 weeks, before sessions for 4 weeks, after sessions for 4 weeks, and then finally, before sessions for 4 weeks. Animals receiving clonidine before daily experimental sessions for the entire period developed tolerance to decreased responding within 3 weeks, and their responding remained near control levels except when clonidine was occasionally preceded by the alpha-2-antagonist yohimbine. Animals receiving clonidine after sessions did not develop tolerance, and responding was markedly suppressed during the first exposure to presession clonidine. When these animals subsequently received clonidine again after sessions, responding was disrupted (increased) in spite of continued drug administration as if animals were "dependent" on clonidine in specific circumstances. When these animals again received clonidine before sessions, responding was partially suppressed in spite of uninterrupted drug administration as if animals had "lost" tolerance in specific circumstances. Tolerance to the behavioral effects of clonidine on fixed-interval responding was not determined by the presence of drug alone, but by the associative influence of drug-related effects in the presence of specific environmental stimuli. PMID- 2217501 TI - Adenosine receptor antagonism accounts for the seizure-prolonging effects of aminophylline. AB - The mechanism of action of aminophylline in prolonging seizures was tested in amygdala-kindled rats. Aminophylline prolonged the afterdischarge duration of kindled seizures. This seizure-prolonging action of aminophylline was strongly antagonized by the adenosine A1 agonist cyclohexyladenosine and partially antagonized by the benzodiazepine partial agonist RO 15-1788. However, the specific benzodiazepine antagonist CGS 8216 did not affect the seizure-prolonging action of aminophylline. Also, the potent anticonvulsant effect of diazepam on kindled seizures, which was completely antagonized by CGS 8216, was unaffected by aminophylline. Furthermore, a range of benzodiazepine inverse agonists, GABA antagonists, phosphodiesterase inhibitors and xanthines did not prolong afterdischarge durations. These results demonstrate that the seizure-prolonging action of aminophylline is due to block of A1 adenosine receptors since it is prevented by adenosine A1 agonists. PMID- 2217503 TI - Vasopressin does not mediate the inhibition of ethanol drinking by the renin angiotensin system. AB - Manipulations which are known to enhance activity in the renin-angiotensin system (RAS) have been found to reduce the voluntary consumption of ethanol in rats. Since angiotensin II is a potent stimulus for the release of vasopressin (VP), it is possible that the RAS modulates ethanol (ETOH) consumption through a mechanism involving VP. The present investigation examined the effect of peripheral injections of arginine-VP (AVP) and desglycinamide-AVP (DGAVP) on ETOH consumption in rats given daily one-hour access to ETOH. Daily subcutaneous treatment with AVP or DGAVP had no effect on ETOH consumption at doses ranging from 2 to 200 micrograms/kg (SC). Blood pressure was substantially elevated following a single 20 microgram/kg injection of AVP, indicating that AVP was biologically active at doses which failed to alter ethanol consumption. These findings indicate the VP does not affect established ETOH drinking and furthermore is not likely a critical factor in the reduction of ETOH intake by the RAS. PMID- 2217504 TI - Adinazolam both prevents and reverses the long-term reduction of daily activity produced by inescapable shock. AB - The behavioral consequences of exposure to stressors such as inescapable shock are usually quite transitory if testing is conducted in an environment different from that in which the stressor was administered. Daily running activity is an exception in that it remains depressed for several weeks following experience with inescapable shock. In the present experiments we found the administration of the triazolbenzodiazepine adinazolam able to both reduce this long-term activity reduction produced by inescapable shock when acutely administered before the inescapable shock, and to reverse the effect when chronically administered after the inescapable shock. Classic 1,4-benzodiazepines such as diazepam have been able to prevent such effects when acutely administered before inescapable shock, but cannot reverse these effects when provided after the inescapable shock. Conversely, classic antidepressants such as desipramine have been unable to prevent these behavioral effects when given before inescapable shock in acute form, but can reverse the effects with chronic administration following the inescapable shock. Our observations that adinazolam can both prevent and reverse the effects of inescapable shock are consistent with reports that this agent has both anxiolytic and antidepressant effects in clinical use. PMID- 2217505 TI - Bright light blocks the capacity of inescapable swim stress to supersensitize a central muscarinic mechanism. AB - Clinical and basic researchers have proposed that muscarinic cholinergic mechanisms mediate some effects of chronic stress. Chronic inescapable (forced) swim stress depletes brain biogenic amines and is used to produce learned helplessness in rats. Behavioral and biochemical characteristics of animals in the state of learned helplessness lead some investigators to believe this condition provides a useful animal model of depression. Inescapable swim stress also produces supersensitivity to the hypothermic effect of the muscarinic agonist oxotremorine in the rat. The authors previously demonstrated that bright light potently induces subsensitivity of a central muscarinic mechanism involved in the regulation of core temperature under a variety of circumstances. They now report using a repeated measures design that inescapable swim stress of five days duration produces supersensitivity to oxotremorine (increase in thermic response of 405%). This supersensitivity is reversed within five days by treatment with bright light, despite continuation of daily swim stress. Daily inescapable swim stress was continued beyond cessation of treatment with bright light. Five days later, supersensitivity to the hypothermic effect of oxotremorine was once again evident. PMID- 2217506 TI - Sensitivity of EEG in young rats to toluene exposure. AB - Effects of toluene on the electroencephalogram (EEG) and its power spectra were measured during a 2-hr exposure in a dynamic inhalational chamber in young rats (30-53 days old) and compared to those in adult rats (63-77 days old). Rats were exposed to one of the three concentrations [low (108-111 ppm), medium (160-163 ppm), and high (407-432 ppm)] of toluene on different days. In tests on sleep wake cycle, in the young animals the duration of the wake stage (W) was increased with decreases of rapid eye movement (REM) and non-REM (NREM) sleep during hr 1 and hr 2 of exposure to the low concentration. These effects were marked at the medium and the high concentrations. In adult rats, at the low concentration the increase of W and the decrease of REM were observed only at hr 1; however, at medium and high concentrations these changes of W and REM sleep were marked along with a decrease of NREM. Comparison of the changes of duration of different states in rats of two age groups showed that there was a significant difference in the increase of W and the decrease of NREM sleep in young rats at hr 2 of exposure to low concentrations only compared to those in adult rats. Tested on power spectrum in young rats during REM sleep recorded from the visual cortex, the power of delta waves increased at the medium and high concentrations and that of theta wave decreased at the high concentration during hr 2 of exposure compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2217507 TI - Central effect of morphine pretreatment on short- and long-term habituation to a danger stimulus in the crab Chasmagnathus. AB - Morphine is believed to inhibit the crab's escape response to a danger stimulus due to central drug action. To test alternative explanations of such an effect in terms of afferent and/or efferent impairment, experiments were conducted using the crab's optokinetic response as indicator. Doses of morphine with maximal detrimental effect on the escape response (75-100 micrograms/g) showed no effect on the optokinetic response, both by measuring the crab's eyestalk displacement and by recording its body rotation, supporting the hypothesis of a morphine central action on the danger-induced escape response. As regards the effect on habituation, a 75 micrograms morphine/g injection administered 30 min before the first trial produced a parallel shift of the short-term (within-session) habituation curve, suggesting a modulatory central drug action that would mimic a putative endogenous opioid action. A 100 morphine micrograms/g dose injected 30 min before training sharply reduced reactivity during training and impaired the acquisition of long-term (between-session) habituation. It may be speculated that the decrease in the danger meaning of the stimulus due to morphine explains both effects in terms of a stimulation impairment during training. PMID- 2217508 TI - Antidepressant-like action of nicardipine, verapamil and hemicholinium-3 injected into the anterior hypothalamus in the rat forced swim test. AB - Male Wistar rats, chronically implanted with cannulas into the anterior hypothalamus, were acutely injected with the calcium channel inhibitors, diltiazem, nicardipine and verapamil, or the choline uptake blocker hemicholinium 3 and tested in the forced swim test. Hemicholinium-3, nicardipine and verapamil markedly increased the duration of active swimming. This antidepressant-like effect did not appear to reflect merely a hyperactive state as the drug-treated rats did not differ from vehicle-injected controls in their open field motility scores. Diltiazem failed to influence rats' performance in either test. Since nicardipine and verapamil, but not diltiazem, share choline uptake property with hemicholinium-3, it seems that this action plays a role in the antidepressant like effect of all three drugs in the forced swim test. PMID- 2217509 TI - Haloperidol impairs classically conditioned nictitating membrane responses and conditioning-related cerebellar interpositus nucleus activity in rabbits. AB - Rabbits, chronically implanted with recording electrodes in the cerebellar interpositus nucleus and following acquisition of a classically conditioned eyelid response, were injected with haloperidol (HAL, 250 micrograms/kg). HAL significantly reduced the number of conditioned responses when a 75 and 85 dB tone conditioned stimulus (CS) was presented but not when a 95 dB tone CS was used. There was a corresponding decrease in interpositus activity at the 75 and 85 dB CS intensities but not at the 95 dB intensity. HAL appeared to disrupt CRs and interpositus activity by increasing the intensity threshold of the tone CS for eliciting conditioned responses. Possible mechanisms for the effect of HAL on neural circuitry involved in classical eyelid conditioning are discussed. PMID- 2217511 TI - Differential effects of psychotropic drugs on feeding in rats: is histamine blockade involved? AB - The present animal studies tested the hypothesis that drug-induced blockade of histamine-1 receptors leads to appetite stimulation. Test agents included the antipsychotic promazine which has very potent antihistaminic effects, as well as the antipsychotic haloperidol and the antidepressant desipramine which both have negligible antihistaminic effects. In support of the hypothesis, significant appetite stimulation occurred only with promazine, while the other two test agents did not increase feeding, and even produced some suppression in food intake. PMID- 2217510 TI - Effects of Mel B arsobal and alpha-difluoromethylornithine on the awakening electroencephalogram of humans with gambiense trypanosomiasis disease: preliminary report. AB - Five males and three females, at the encephalic stage of sleeping sickness, were submitted to trypanocide therapies. Three of the patients were treated with the Mel B Arsobal drug, the five others with difluoromethylornithine, using different protocols. Awakening electroencephalographic data were obtained prior to treatment and, at regular intervals, during and after treatment. Prior to treatment the awakening tracings showed important abnormalities (slow delta waves were superimposed on theta background rhythms). During treatment (except in one patient treated with Arsobal) recordings returned gradually to fast rhythms and several days after therapy, tracings returned to the normal awakening patterns. The use of the awakening electroencephalogram as a tool to test effects of curative drugs in the sleeping sickness syndrome is discussed. PMID- 2217512 TI - SCH 23390: D-1 modulation of oral dyskinesias induced in snakes by Xenopus skin mucus. AB - The granular gland skin secretion of Xenopus laevis induces seven involuntary oral dyskinesias and climbing behavior in the water snake Nerodia sipedon. In a previous study the D-2 receptor antagonist, haloperidol (HAL), selectively potentiated mucus-induced yawning and chewing but attenuated fixed gaping; other oral behaviors were unaffected; HAL alone induced no dyskinesias and failed to modify mucus-induced decreases in tongue flicking, cage climbing and activity. As skin compounds have neuroleptic properties known to induce human and animal dyskinesias, we hypothesized that D-1 receptor antagonism may modulate the four of seven mucus-induced dyskinesias and the climbing not altered by HAL. We found that, like HAL, SCH 23390 (SCH) potentiated mucus-induced yawning, attenuated fixed gaping and had no effect on climbing. Unlike HAL's potentiation of chewing, SCH attenuated chewing and potentiated writhing tongue movements. SCH alone, like skin mucus, attenuated tongue flicking and activity but, given with mucus, SCH increased tongue flicking and activity to control levels. Compared to the HAL study, results suggest that mucus-induced yawning and fixed gaping are similarly modulated by both HAL and SCH, while these drugs have opposite effects on writhing tongue and chewing. SCH given alone or with frog mucus had unique effects on activity and normal tongue flicking. PMID- 2217514 TI - Tonic nociception in neonatal rats. AB - The issues of whether infants detect noxious stimuli and whether their nociceptive responses are suppressed by analgesics has been the focus of considerable controversy. Therefore, to more completely assess the nociceptive responses of neonatal rat pups to tonic pain, we tested 3-day-old rat pups using the formalin test. The responses of the young pups to formalin-produced injury were similar to those observed in adult rats, both behaviorally and in terms of their responsivity to morphine-induced antinociception. These results provide the first clear-cut evidence of integrated tonic pain responses in the neonate. PMID- 2217513 TI - Physostigmine facilitation of lordosis in naturally cycling female rats. AB - Both systemic and intracerebral administrations of the cholinergic muscarinic antagonist, scopolamine, have been shown to inhibit naturally occurring sexual behavior in intact, cycling female rats. The present study examined the facilitative effects of the acetylcholinesterase inhibitor, physostigmine (eserine), on sexual behavior in intact, cycling female rats. Cycling was determined by daily monitoring of sexual behavior and vaginal cytology. When administered during either early proestrus or proestrus, physostigmine activated lordosis 15 min and 1 hr after intraventricular infusion (10 micrograms bilaterally). However, infusion of physostigmine failed to facilitate lordosis 15 min after administration during either diestrus I, mid-diestrus, or diestrus II. The administration of this cholinergic agent did not interrupt cyclicity patterns. Because estrogen levels are highest during proestrus and cholinergic facilitation appears to be limited to this time, it is suggested that estrogen priming of central cholinergic systems is necessary for the cholinergic regulation of sexual behavior in intact, cycling female rats. PMID- 2217515 TI - Microinfusion of bombesin into the hypothalamic paraventricular nucleus produces hypothermia in the insulin-pretreated rat. AB - Bombesin-like peptides are widely distributed in the mammalian central nervous system and participate in the regulation of a variety of autonomic functions. Central injection of bombesin produces hypothermia at normal ambient temperatures, but only if the rat has been food-deprived or made hypoglycemic with insulin. Two experiments were conducted to reevaluate the impact of bombesin microinfusion into the hypothalamic paraventricular nucleus (PVN) on core body temperature and feeding behavior. In Experiment 1, bombesin (0.05 and 0.1 microgram/1.0 microliter) produced hypothermia, but not hypophagia, in rats (n = 5) pretreated with insulin (10 U/kg; IM). Since a similar response was observed in rats with injection sites adjacent to the PVN, a smaller injection volume was evaluated in Experiment 2. Hypothermia, but not hypophagia, was observed in rats (n = 5) pretreated with insulin following bombesin (0.025 and 0.05 micrograms/0.5 microliter). Bombesin did not produce hypothermia in rats with injection sites outside of the PVN. These findings suggest that the PVN is a sensitive site for bombesin-induced hypothermia. PMID- 2217516 TI - The effects of cocaine on food intake of baboons before, during, and after a period of repeated desipramine. AB - Food intake of five adult male baboons (Papio c. anubis) was monitored during daily 22-hr experimental sessions. Food was available under a chain schedule with two components. Following completion of the "procurement" component, the first response requirement, access to food, i.e., a meal, became available under the second, "consumption" component, during which each response produced a 1 g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. Complete dose-response functions for cocaine (0.50-4.0 mg/kg, IM) and desipramine (0.50-4.0 mg/kg, IM), were determined before, during, and after a period of repeated administration of desipramine. Cocaine produced dose-dependent increases in the latency to initiate feeding and decreases in food intake during the first eight hr of the session. Compensatory feeding occurred later in the session so that cocaine had no effect on total daily intake. There was no interaction between repeated desipramine and the acute effects of cocaine. Desipramine produced dose-dependent decreases in intake during the first two hr of the session, the size of the first meal and intake during the entire session. These measures, as well as number of meals and second meal size, remained below baseline during repeated desipramine. Thus, repeated desipramine, while having significant effects on feeding behavior itself, did not influence the effects of cocaine administration on food-maintained responding. PMID- 2217518 TI - Sensitization versus tolerance to haloperidol-induced catalepsy: multiple determinants. AB - The effects of dose, administration frequency, and behavioral testing conditions on the development of tolerance versus sensitization to haloperidol-induced catalepsy were tested in rats. Animals received daily or weekly injections of haloperidol (0.05-5.00 mg/kg SC) for up to 22 days. Catalepsy assessments were made either once or repeatedly using two tests: the horizontal bar and the inclined screen. Tolerance was found only in animals treated daily with haloperidol (1.5 mg/kg) and tested repeatedly on the horizontal bar. In contrast, sensitization was observed with various haloperidol doses, daily or weekly administration schedules (for most doses), either horizontal bar or inclined screen catalepsy tests, and repeated or single testing. Sensitization developed most strongly following weekly drug administration and repeated testing on the horizontal bar. No single experimental variable produced a definitive pattern of change in catalepsy over time. Dose, drug administration schedule, and behavioral test conditions all influenced the evolution of catalepsy during chronic haloperidol treatment. PMID- 2217517 TI - Sodium arsanilate-induced vestibular dysfunction in rats: effects on open-field behavior and spontaneous activity in the automated digiscan monitoring system. AB - Vestibular dysfunction was chemically induced in Long-Evans rats by intratympanic injections (30 mg per side) of sodium arsanilate (atoxyl). Following a one-week recovery period the rats were behaviorally assayed for integrity of the labyrinthine systems. All subjects were tested for presence of the air-righting reflex, the contact-righting reflex (by lightly holding a sheet of Plexiglas against the soles of the rat's feet), and body rotation-induced nystagmus. All animals were then tested for their ability to remain on a small (15 x 15 cm) platform. Next, the subjects were given two 10-min open-field tests during which ambulation, rearing, grooming, and defecation responses were recorded. Four to five weeks later all rats were tested twice (60 min per session) in the automated Digiscan Activity Monitor which provides a multivariate assessment of spontaneous motor activity. The rats with vestibular dysfunction (Group VNX) took significantly less time to fall off the platform (p less than 0.01). They also exhibited significantly more open-field ambulation but fewer rearing responses (ps less than 0.01). An examination of group correlation coefficients for open field variables and the platform test scores revealed some interesting group differences (ps less than 0.05). In the Digiscan tests the atoxyl-treated rats exhibited fewer number of horizontal movements, but increased speed for these movements (ps less than 0.05). Vertical movements did not differ significantly in incidence, but these movements were greatly reduced in duration (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2217520 TI - Chronic stress and memory: implication of the central cholinergic system. AB - Restraint stress for ten days (two times two hours daily) induces a hypersensitivity of the central cholinergic system, reflected by antagonism to amnesia induced by scopolamine at 0.1 mg/kg in a passive avoidance test and by hypersensitivity to the hypothermic effect of oxotremorine at 1 mg/kg. A restraint stress for 30 days, on the other hand, diminishes animal retention in the passive avoidance test and causes a hyposensitivity to oxotremorine-induced hypothermia, reflecting a hypoactivity of the central cholinergic system. An acute 24-hour stress causes no change. The relationship between chronic stress and associated memory deficits is discussed. PMID- 2217519 TI - Cocaine and body temperature in the rat: effect of exercise. AB - The laboratory rat is being studied as a model to determine if abuse of cocaine constitutes a risk factor in the pathogenesis of stress or exertion induced heatstroke. During running on a treadmill for 60 min under thermoneutral conditions (Ta 22 degrees C) a rise in core temperature of approximately 1 degree C was recorded. Injection of cocaine (10 or 20 mg/kg IP) or its vehicle (0.9% NaCl solution) did not modify the running behavior or the core temperature change. Cocaine (30 mg/kg IP) led to a significant increase in the core temperature (compared to animals treated with saline or the lower doses of cocaine) at 45 and 60 min. The rats recovered rapidly following cessation of exercise. Repeated (3) injections of cocaine (30 mg/kg) at 7-day intervals did not alter the magnitude of the final hyperthermia, i.e., neither tolerance nor potentiation were in evidence. PMID- 2217521 TI - Ethanol reduces tolerance, sensitization, and up-regulation of D2-receptors after subchronic haloperidol. AB - To study the interrelationships between dopamine D2-receptor density and behavioral responses after chronic treatment with neuroleptics female Wistar rats received haloperidol (HP; 14 mg/l), ethanol (ETOH; 5 vol.%), a combination of both, or tap water as drinking fluids for one or two weeks. Mean intake doses ranged between 1.28 and 1.48 mg/kg/day (HP) and between 3.7 and 4.8 g/kg/day (ETOH). HP administered for one or two weeks raised the number of [3H]spiroperidol binding sites in the striatum by 55%. Concomitant administration of ETOH diminished the increase of Bmax to 23%. The up-regulation was even reversed when ETOH was added with a delay of one week, although the drug alone had no effect on dopamine-D2-receptor density. KD values were not substantially affected. During HP treatment the rats established a tolerance to the motor sedation which was measured by circadian motility recordings. Coadministration of ETOH reduced the development of tolerance, the activity remained at a depressed level. Acute applications of HP (0.3, 0.6, and 0.9 mg/kg, or saline, respectively) also revealed tolerance to the drug for various behavioral responses (exploratory locomotion, rearing, rotarod performance, catalepsy). The tolerance was reduced in all those animals which had received combinations of ETOH and HP. The reduction was most pronounced for the cataleptic response. Pretreatment with ETOH alone had no effect. Sensitization to dopamine agonists was studied by apomorphine-induced stereotypies (licking, sniffing, and forepaw scratching). As expected, chronic HP enhanced the responses. The increased number of stereotypies was reduced in rats pretreated with the combination, although ETOH alone did not affect the response. The reduction was most pronounced for licks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2217522 TI - Differential actions of RO 15-1788 and diazepam on poikilothermia, motor impairment and sleep produced by ethanol. AB - In adult male Sprague-Dawley rats kept at an ambient temperature of 23-25 degrees C, ethanol was injected intraperitoneally in a dose of 4.0 g/kg to produce a clear-cut impairment of autonomic and motorial functions. Following the injection of ethanol, motor coordination, measured on a rotorod, behavioral sleep, righting reflex and colonic temperature were monitored at predetermined intervals for 5.0 7.0 hr. In the first experiment, either 1.0 mg/kg RO 15-1788 (flumazenil), a benzodiazepine (BZ), receptor antagonist, or 1.0-5.0 mg/kg diazepam, a classical benzodiazepine receptor agonist, were injected intraperitoneally either alone or concurrently with ethanol's administration. In the second study, either RO 15 1788 (1.0 or 2.0 mg/kg) or diazepam (1.0 or 5.0 mg/kg) was injected at the nadir of the fall of body temperature induced by ethanol. Although RO 15-1788 alone failed to affect the rats' temperature, it did not prevent the characteristic ethanol-induced hypothermia but rather potentiated it in a dose-dependent manner. Further, this BZ receptor antagonist exacerbated motor incoordination and other behavioral effects when given either simultaneously with ethanol or at the nadir in the animals' core temperature. Although diazepam evoked a dose-dependent hypothermia, it did not enhance ethanol-induced hypothermia when both drugs were administered simultaneously. However, diazepam augmented motor incoordination and other effects and served to delay their recovery. When given to the rats at the nadir of ethanol hypothermia, diazepam did not potentiate ethanol's thermolysis but retarded the recovery from hypothermia; it caused also a dose-dependent delay in the recovery of motor coordination and other responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2217523 TI - Learning abilities of rats in multiple T-mazes of two degrees of complexity under the influence of d-amphetamine. AB - The effect of d-amphetamine on the learning capacity of male Wistar rats was investigated in multiple T-mazes in two experiments of increasing or decreasing degree of difficulty. Running speed, distance covered and the number of errors were scored to indicate proficiency and success of learning. These parameters, as well as the distribution of errors (goal-directed orientation), correction of errors (situational orientation) and latency at the decision points (discrimination time) were considered to represent cognitive components. The results demonstrated an experiment effect in that the rats showed more difficulty in learning, as exhibited by a slower running speed and more errors, in the maze with successively increasing demands than in the one with decreasing demands. Oral self-administered d-amphetamine in a dosage of 3-4 mg/kg/day or 7-8 mg/kg/day significantly increased the running speed in a dose-dependent manner. By contrast, success of learning and goal-directed orientation decreased. Situational orientation was, however, dose-dependently improved, at least in the experiment with the increasing demand. PMID- 2217524 TI - Dose effects on heart rate conditioning when pentobarbital is the CS and amphetamine is the US. AB - If sodium pentobarbital is injected into rats 30 min prior to d-amphetamine sulphate on four or five occasions, there is a learned effect of pentobarbital on heart rate. The conditioned response is a higher heart rate than found in rats with a control history of exposure to the same drugs. In Experiment 1, when the pentobarbital dose was 32 mg/kg throughout, this effect was obtained with amphetamine doses of 2, 4, 8, or 16 mg/kg. In Experiment 2, when the amphetamine dose was 12 mg/kg throughout, pentobarbital doses of 16 and 32 mg/kg yielded conditioning, while 8 mg/kg yielded equivocal results. PMID- 2217525 TI - Pentobarbital attenuates stress-induced increases in noradrenaline release in specific brain regions of rats. AB - To examine whether anxiolytic action of drugs acting at the GABA/BZD-chloride channel complex may be related to the brain noradrenergic system, we investigated the effect of pentobarbital, a typical barbiturate which has potent GABA modulating properties, on increased NA release in nine brain regions of stressed rats. Pentobarbital (10 and 25 mg/kg) was injected IP 65 min before sacrifice (5 min before one-hour immobilization stress). Levels of 3-methoxy-4 hydroxyphenylethyleneglycol sulfate (MHPG-SO4), the major metabolite of brain noradrenaline (NA), and of plasma corticosterone, were fluorometrically determined. Pentobarbital treatment by itself increased MHPG-SO4 levels in the thalamus, locus coeruleus (LC) region, midbrain and basal ganglia of nonstressed rats. Stress produced increases in MHPG-SO4 levels in all brain regions examined and elevation of plasma corticosterone levels. Pentobarbital attenuated, in a dose-dependent manner, stress-induced increases in MHPG-SO4 levels in the hypothalamus, thalamus, anterior cerebral cortex, LC region and basal ganglia and also attenuated the stress-induced elevation of plasma corticosterone levels. These data suggest that pentobarbital can attenuate both stress-induced increases in NA release in specific brain regions as well as activation of the hypothalamo pituitary-adrenocortical system. These attenuating effects may be related to the anxiolytic action of barbiturates. PMID- 2217526 TI - Comparison of DuP 996, with physostigmine, THA and 3,4-DAP on hypoxia-induced amnesia in rats. AB - DuP 996, 3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one, physostigmine (PH), tetrahydroaminoacridine (THA) and 3,4-diaminopyridine (3,4-DAP) were compared for their ability to protect against hypoxia-induced performance deficits in a passive avoidance (PA) task. The ability to retain PA response was found to decrease as the oxygen concentration decreased with the largest retention deficit occurring at 6.5% oxygen. DuP 996 (0.01-0.1 mg/kg SC), 3,4-DAP (0.1-10.0 mg/kg SC), THA (0.3-5.0 mg/kg SC) and PH (0.001-0.1 mg/kg SC) administered one minute after PA training produced dose-dependent increases in retention latencies following exposure to 6.5% oxygen. In comparing each compound for side effects, DuP 996 induced tremor and mortality at 10 and 40 mg/kg SC, respectively, and PH at 0.3 and 0.8 mg/kg SC, respectively. With PH the 0.3 mg/kg SC dose also produced hypersalivation and a decrease in lift strength. THA produced tremor and mortality at 6.0 and 40 mg/kg SC, respectively, and 3,4-DAP at 50 and 200 mg/kg SC, respectively. 3,4-DAP also produced chromodacryorrhea and hypersalivation at 50 mg/kg SC. Dividing the dose necessary to produce mortality by the highest effective dose active in the hypoxia test yielded a safety ratio for DuP 996 of 400, for 3,4-DAP 20, for PH 8, and for THA 8, showing a greater safety margin for DuP 996 than the other cholinergic agents. These results suggest that DuP 996 may be of use in the treatment of diseases associated with cognitive impairment and may have a greater safety margin than other cholinergic agents. PMID- 2217527 TI - Effects of an extract of Ginkgo Biloba (EGB 761) on "learned helplessness" and other models of stress in rodents. AB - The effects of repeated oral administration of an extract of Ginkgo Biloba (EGB 761) on various behavioral models of stress in rodents were investigated. The models in rats included "learned helplessness," shock-suppressed licking (Vogel conflict test) and forced swimming-induced immobility ("behavioral despair"). The models in mice included shock-suppressed exploration (four plates test), spontaneous exploration (staircase test) and food consumption in a novel situation (emotional hypophagia). Further tests in rats examined the effects of EGB 761 on memory (passive avoidance test) and responsiveness to shock to determine whether the preventive effects observed with EGB 761 in the learned helplessness procedure were due either to drug-induced impairment of memory or to reduced shock sensitivity. In all experiments EGB 761 was administered over 5 days at daily doses of 50 and 100 mg/kg PO. In some experiments (Vogel test, four plates test, staircase test, emotional hypophagia) the effects of acute administration were also investigated. The results showed that repeated administration of EGB 761 (50 and 100 mg/kg/day) before exposure to unavoidable shock (preventive treatment) clearly reduced the subsequent avoidance deficits in the learned helplessness procedure but was less effective when first administered after "helplessness" induction (curative treatment). EGB 761 did not affect performance in the passive avoidance task or alter the animals' response to electric shock, suggesting that the effects observed in the learned helplessness procedure were not due to impaired memory or reduced shock sensitivity. Anxiolytic-like activity was also seen in the emotional hypophagia test in mice where repeated administration of EGB 761 increased the amount of food consumed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2217528 TI - Ouabain injected into the hypothalamus elicits pressor responses in anaesthetized rats: a mapping study. AB - Cardiac glycosides are known to have a narrow therapeutic index, due in part to their effects on the brain. Injections of cardiac glycosides into the ventricles of the brain elicit activation of the autonomic nervous system, and may even elicit cardiac arrhythmias. However, the specific brain regions responsible for such action are unknown. The hypothalamus receives chemo- and baro-receptive innervation from the cardiovascular system. In turn, there are both direct and indirect effector pathways from the hypothalamus accessing the sympathetic preganglionic and parasympathetic ganglia regions. This suggests that the hypothalamus may be a prime candidate for the central toxic effects of cardiac glycosides. The purpose of this experiment was to map the rostral diencephalon to determine sites at which injections of a low dose of the cardiac glycoside, ouabain, resulted in altered cardiovascular responses in the anaesthetized rat. Microinjections of 20 ng of ouabain in 200 nl were made into sites throughout the rostral diencephalon of urethane (1.2 g/kg) anaesthetized rats while monitoring heart rate and blood pressure. Injections into the nucleus medianus, paraventricular, anterior and posterior hypothalamic nuclei produced increases in pressure of from 5 to 25 mmHg. These data suggest that part of the toxicity resulting from the cardiac glycoside administration may be due to the direct action of the glycosides on these hypothalamic structures. The paraventricular region has the greatest sensitivity and may be a primary target due to its direct connections with the preganglionic sympathetic regions in the spinal cord. PMID- 2217529 TI - Effects of fixed-ratio requirement on observed tolerance to decreased responding by clonidine. AB - Responding of rats was maintained under either a 10- or a 40-response fixed-ratio schedule, and "local" rates of responding were 0.29-0.37 responses per sec for both schedules. Clonidine decreased responding for both schedules in a similar and dose-dependent manner, and the largest dose tested (0.3 mg/kg) completely suppressed behavior. When 0.1 mg/kg was administered immediately prior to 30 daily experimental sessions, FR10 responding recovered to control levels within 15 sessions, whereas FR40 responding recovered only to approximately 60% of control level at asymptote. These results continue to identify boundary conditions for the influence of reinforcer loss on tolerance development, and they emphasize the overriding influence of behavioral processes on observed tolerance to the behavioral effects of drugs. PMID- 2217530 TI - Pharmacology of drugs that alter multidrug resistance in cancer. PMID- 2217531 TI - Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. PMID- 2217532 TI - The roles of nurses' associations and individual nurses in promoting health by safeguarding the environment. PMID- 2217533 TI - Twelve tips to protect your environment and your health (World Health Organization). PMID- 2217534 TI - Philippine population development: a nursing concern. PMID- 2217535 TI - In vivo measurement of total body carbon using 238Pu/Be neutron sources. AB - Total body carbon has been measured by in vivo neutron activation analysis (IVNAA) in 278 surgical gastroenterological patients and 29 normal volunteers. This is based on the inelastic scattering reaction [12C (n,n') 12C*] for neutrons with energy above 4.8 MeV, producing 4.43 MeV gamma rays. Since only part of the body is scanned, total body carbon is estimated as the ratio of the gamma ray emission from carbon to the emission from hydrogen, using hydrogen as the internal standard. The precision of the estimate is +/- 1.6 kg for a whole body dose of 0.3 mSv. There is a significant difference between the estimates of total body water from IVNAA measurements of carbon and nitrogen and measurements of body water in these subjects by tritium dilution (t = 3.1, p less than 0.005). PMID- 2217536 TI - Automatic computer detection of clustered calcifications in digital mammograms. AB - The automatic detection of clusters of calcifications in digital mammograms has been investigated using image analysis techniques. The calcifications were segmented from the background of normal breast structure in the mammogram using a local area thresholding process. This procedure also identified other breast structures and the digital image properties of all segmented objects were analysed to extract clusters of calcifications. Seventy five clinical mammograms were digitised. These were divided into training and test sets of 25 and 50 films respectively. The results for the test set of 50 complete clinical mammograms show that the computer system achieves a 25/25 true positive film classification (i.e. those containing clusters of calcifications) with false positive clusters detected in 4/50 films. There were no false negative film classifications. PMID- 2217537 TI - The distribution of induced currents in magnetic stimulation of the nervous system. AB - Magnetic stimulation of the nervous system is being used as an alternative to electrical stimulation, principally because it is painless. The spatial distribution of induced currents from the stimulating coil is calculated from a computer model with graphical output. Two configurations of a plane circular coil are considered: parallel to the tissue surface and perpendicular to the surface. The surface is assumed planar and infinite in extent. The tissue is modelled as a uniform, isotropic volume conductor. A quasi-static approximation is made in calculating the electric field. Maps of current density, J, as a function of position, including depth, are shown. In both configurations, J is always parallel to the surface, and is maximum at the surface. There is no perpendicular (vertical) current. For a one-turn 10 cm diameter coil, spaced 1 cm from conducting tissue and parallel to it, with rate of change of current 10(8) A s( 1), Jmax = 6.8 A m(-2) (assuming conductivity 0.2 omega -1 m(-1)). In the perpendicular configuration Jmax = 4.1 A m(-2). These results suggest that nerve fibres running parallel to the skin surface are more likely to be stimulated than those running obliquely; and that it is extremely difficult to stimulate nerve fibres running perpendicularly. This model can be used to characterise the performance of other shapes of stimulating coils and the dependence on fibre orientation. PMID- 2217538 TI - Explosive onset of continuous wave laser tissue ablation. AB - The phenomena at the onset of and during tissue ablation using continuous wave lasers were studied. Aortic and myocardial bovine tissues were exposed in air and in water to Nd-YAG (10 to 60 W) and argon (3.5 W) laser light. The transmitted light was measured, the surface of the tissue was filmed and the tissue was processed for histology. Three distinct phases were observed. Phase A was tissue denaturation. Phase B started with explosive vaporisation ('popcorn') in conjunction with a drop of about 50% in light transmission due to enhanced reflection and scattering. The 'popcorn' is possibly associated with a layered structure of the tissue. Phase C started with carbonisation of the tissue beginning in the centre and expanding in a cyclic fashion while the tissue was vaporised leaving a crater. Forward light transmission did not decrease. Thin layers of carbon (20 microns) and vacuoles (30 microns) suggested a large temperature gradient along the tissue ablation front. The ablation velocity was constant (r greater than 0.92) and tissue dependent. Reported models on laser tissue ablation need to be extended to include explosive vaporisation ('popcorn') at the onset and cyclic carbonisation during steady-state crater formation. PMID- 2217539 TI - Concurrent and construct validity of the Pediatric Evaluation of Disability Inventory. AB - The purpose of this study was to determine the validity of the Development Edition (pilot version) of the Pediatric Evaluation of Disability Inventory (PEDI) in groups of disabled and nondisabled children. The PEDI is a new functional assessment instrument for the evaluation of disabled children aged 6 months to 7 years. The PEDI has been developed to identify functional status and change along three dimensions: 1) functional skill level, 2) caregiver assistance, and 3) modifications or adaptive equipment used. The PEDIs were administered as a parental-report questionnaire, and the results were compared with data obtained by the Battelle Developmental Inventory Screening Test (BDIST). The BDIST is a standardized assessment with developmental and adaptive content. Subjects were 20 children between the ages of 2 and 8 years with arthritic conditions and spina bifida and 20 nondisabled children matched for age and sex. All subjects' scores on the BDIST cognitive domain were no greater than 1.50 standard deviations below the mean for their age group. Concurrent validity was supported by moderately high Pearson product-moment correlations between BDIST and PEDI summary scores (r = .70-.80). Construct validity was supported by significant differences between the disabled and nondisabled groups' PEDI scores and by discriminant analysis identifying the PEDI scores as better group discriminators than the BDIST scores. Results validate the Developmental Edition of the PEDI and support the further development and standardization of the final version. Use of the PEDI in clinical pediatric physical therapy practice is discussed. PMID- 2217541 TI - Preservation of force output through progressive reduction of stimulation frequency in human quadriceps femoris muscle. AB - The purpose of this study was to determine the effects of a reduction in the pulse frequency on the fatigue rate of human quadriceps femoris muscle during intermittent (8-second) contractions. Twelve healthy subjects each participated in two experimental sessions. Thirty cycles (cycle time: 8 seconds "on"/12 seconds "off") were applied during each session. During one session, a frequency of 60 pulses per second (pps) was used for all trains. During the other session, the subjects were stimulated with 60 pps for the first train. The stimulating frequency of each train was then progressively reduced, in 5-pps steps, for contractions 2, 3, 5, 8, 12, and 20. By the fifth contraction, the differences in average force produced by the 60-pps trains and the reduced-frequency trains were significant. The difference between the two conditions increased, with the variable-frequency protocol producing 46% more force than the constant-frequency protocol during the last contraction. These results showed that, compared with a constant pulse frequency, reducing the pulse frequency during a fatiguing contraction can markedly decrease the rate of force fatigue of skeletal muscle. This finding suggests that a variable-frequency protocol, similar to the one used in this may prove to be a more effective pattern of stimulation for activation of skeletal muscle than the traditionally used constant-frequency protocol. PMID- 2217540 TI - Lumbar curvature in standing and sitting in two types of chairs: relationship of hamstring and hip flexor muscle length. AB - A purpose of this study was to determine the difference in the lumbar curves of subjects while they stood compared with while they sat in two chairs with different seat angles--the Balans Multi-Chair (BMC) and a standard conventional chair (SCC). An additional purpose was to determine the relationship between lumbar curvature and 1) anthropometric factors and hamstring and hip flexor muscle length during standing and during sitting in the two chairs and 2) amount of time spent sitting. Sixty-one men between 20 and 30 years of age served as subjects. Lumbar curve measurements were taken with a flexible ruler with the subjects first standing and then sitting in the two chairs. Hamstring and hip flexor muscle lengths were indicated by range-of-motion measurements taken with a gravity goniometer. Age, number of hours spent sitting per day, upper body length, and right leg length also were recorded. Subjects had significantly more lumbar extension when they sat in the BMC than when they sat in the SCC. Hip flexor length was the only factor that appeared to relate significantly to the difference between the standing lumbar curve and the lumbar curves in the BMC and the SCC. PMID- 2217542 TI - Effects of neuro-developmental treatment and orthoses on knee flexion during gait: a single-subject design. AB - The interactive effects of neuro-developmental treatment and inhibitive ankle height orthoses on gait were examined via a single-subject research design. Knee flexion during gait at initial contact, mid-stance, heel-off, and mid-swing were measured in a 2-year-old girl with diplegia by use of a goniometer and freeze frame videography. During the treatment and treatment/orthoses phases, a decrease in excessive knee flexion was noted. Changes in trend over time were greater in the 3-week treatment phase than in the 3-week treatment/orthoses phase. Changes in level at the initiation of the treatment/orthoses phase were greater than in the treatment phase. The described neuro-developmental treatment activities were conducted correctly 92% of the time according to an independent observer. The interrater reliability of goniometric data measured by videography was .93 using intraclass correlation coefficients. The results of this study suggest that both methods of treatment can be used to decrease excessive knee flexion during gait in a child with diplegia. PMID- 2217544 TI - Conditioning of the spinal stretch reflex: implications for rehabilitation. AB - The purpose of this article is to describe a new technique that can potentially be applied to patients with hyperactive spinal stretch reflexes (SSRs). The progression of clinical research from conditioning of individual muscles or muscle groups (electromyographic biofeedback) to conditioning SSRs is explained. Research data from subhuman primates in addition to the first human experiments are reviewed. Potential applications of SSR conditioning are discussed, as are the issues requiring further delineation and research before the specificity of a training effect can be ascertained. PMID- 2217545 TI - Body-composition assessment using underwater weighing techniques. AB - Health care professionals recommend that assessment of body composition be included as a part of an adult fitness program. Underwater weighing, based on Archimedes' principle, is the most valid technique for assessment of percentage of body fat and lean tissue in a clinical setting. This article presents a computer program written in BASIC that performs all of the decision-making calculations and provides the user with a tabular and a graphical summary of current body composition in addition to recommendations for changes in body composition that will enhance the subject's health. PMID- 2217543 TI - Whole-body movements during rising to standing from sitting. AB - Rising to a standing position from a sitting position is one of the most important activities of daily life. We present a total-body analysis of rising from a chair as performed by nine healthy individuals under controlled conditions. We describe four phases of this activity. Phase I is a flexion momentum phase used to generate the initial momentum for rising. Phase II begins as the individual leaves the chair seat and ends at maximal ankle dorsiflexion. Forward momentum of the upper body is transferred to forward and upward momentum of the total body. Phase III is an extension phase during which the body rises to its full upright position. Phase IV is a stabilization phase. Kinetics and kinematics of the phases are analyzed. The phases are differentiated in terms of momentum and stability characteristics. Clinical implications of the mechanics of rising are discussed. PMID- 2217546 TI - Cell membrane DNA: a new target for psoralen photoadduct formation. AB - The effects of 8-methoxypsoralen plus long wavelength ultraviolet radiation on cell membrane DNA were examined. Treatment of human lymphocytes with 100 ng/ml 8 methoxypsoralen and 5 J/cm2 UVA led to the formation of 7.1 +/- 3.8 photoadducts per million bases. A monoclonal antibody, specific for 8-methoxypsoralen 4',5' monoadducts, was used to detect photoadducts in the cell membrane DNA of human lymphocytes and three lymphoblastoid cell lines. Treatment of lymphocytes with 8 MOP and UVA reduced the lymphocyte DNA binding capacity by 56%. Cell membranes of normal lymphocytes were shown to contain three high affinity DNA binding proteins of 28, 59, and 79 kDa, respectively. PMID- 2217547 TI - Quinone sensitized electron transfer photooxidation of nucleic acids: chemistry of thymine and thymidine radical cations in aqueous solution. AB - The 2-methyl-1,4-naphthoquinone (MQ) sensitized photooxidation of nucleic acid derivatives has been studied by laser flash photolysis and steady state methods. Thymine and thymidine, as well as other DNA model compounds, quench triplet MQ by electron transfer to give MQ radical anions and pyrimidine or purine radical cations. Although the pyrimidine radical cations cannot be directly observed by flash photolysis, the addition of N,N,N',N'-tetramethyl-1,4-phenylenediamine (TMPD) results in the formation of the TMPD radical cation via scavenging of the pyrimidine radical cation. The photooxidation products for thymine and thymidine are shown to result from subsequent chemical reactions of the radical cations in oxygenated aqueous solution. The quantum yield for substrate loss at limiting substrate concentrations is 0.38 for thymine and 0.66 for thymidine. The chemistry of the radical cations involves hydration by water leading to C(6)-OH adduct radicals of the pyrimidine and deprotonation from the N(1) position in thymine and the C(5) methyl group for thymidine. Superoxide ions produced via quenching of the quinone radical anion with oxygen appear to be involved in the formation of thymine and thymidine hydroperoxides and in the reaction with N(1) thyminyl radicals to regenerate thymine. The effects of pH were examined in the range pH 5-8 in both the presence and absence of superoxide dismutase. Initial C(6)-OH thymine adducts are suggested to dehydrate to give N(1)-thyminyl radicals. PMID- 2217549 TI - Theoretical study of electronic spectra and photophysics of uracil derivatives. AB - The changes that the UV absorption spectrum and the photophysics of uracil undergo under hydrogen substitution or deprotonation, were studied theoretically within the CS-INDO/CI scheme. First of all this method was tested on uracil. It was then used for the calculation of the electronic structure of excited states (Sn, Tn) of a large number of uracil derivatives (1-, 3- and 5-methyluracil; 1,3 , 1,5- and 3,5-dimethyluracil; 5-fluoro- and 5-chlorouracil), including some anions (1- and 3-methyluracil anion). The excited states were obtained in the singly-excited configuration interaction approximation (S-CI) and the correlation effects on (pi pi*) states were studied by including the most important doubly- and triply-excited configurations in the CI. The S-CI wavefunctions were used for the calculation of the most important electronic matrix elements for spin-orbit coupling. The photophysics of these compounds is discussed using Jablonski diagrams. PMID- 2217548 TI - Anthralin-derived transients--II. Formation of the radical by spontaneous fragmentation of both singlet and triplet states of the 10,10'-dehydrodimer: radical pair multiplicity effects. AB - The singlet and triplet states of the anthralin (1,8-dihydroxy-9-anthrone) dehydrodimer have been produced selectively in benzene via pulsed laser excitation and pulse radiolysis respectively. The lifetime of S1 is less than or equal to 30 ps, that of T1 short but unspecified. Both states fragment spontaneously to yield a pair of anthralin radicals. The singlet radical pair predominantly undergoes geminate recombination within the solvent cage. In contrast, the corresponding triplet radical pair undergoes essentially exclusive cage escape to give the anthralin free radical (lambda max 370, 490 and 720 nm) which recombines under normal diffusive conditions. Both recombination processes lead, at least in part, to one or more species which have been assigned as tautomeric forms of the original dimer. The anthralin free radical in benzene is insensitive to the vitamin E model 6-hydroxy-2,2,5,7,8-pentamethylchroman and reacts only slowly with oxygen. PMID- 2217550 TI - Ultraviolet light induces double-strand breaks in DNA of cultured human P3 cells as measured by neutral filter elution. AB - Neutral filter elution at pH 7.2 and 9.6 was used to measure the induction of DNA lesions in human P3 teratocarcinoma cells by monochromatic 254-, 270-, 313-, 334 , 365-, and 405-nm radiation and by 60 gamma rays. In this assay DNA double strand breaks (dsb) increase the rate of elution of DNA from cell lysates on a filter. Yields of dsb as measured by this procedure were determined by using a calibration of the assay that correlates elution parameters with number of dsb caused by disintegration of 125I incorporated into the DNA. Analysis of fluence responses obtained by using the calibrated assay indicated that the number of dsb induced per dalton of DNA as measured by this assay is proportional to the square of the fluence at all the energies of radiation studied, implying that the induction of these lesions may be a two-hit event. Analysis of the relative efficiencies for the induction of dsb by ultraviolet radiation, corrected for quantum efficiency, revealed a spectrum that coincided closely with that for the induction of single-strand breaks (ssb) in the same cells, having a close fit with the spectrum of nucleic acid in the UVC and UVB region below 313 nm, and a shoulder in the UVA region. It was calculated, however, that there may be too few ssb for dsb to result from randomly distributed closely opposed ssb. PMID- 2217552 TI - Time-resolved luminescence spectroscopy of photosensitizers of biomedical interest. AB - Studying the fluorescence decay of chromophores, either used as fluorescent labels to stain specific biomolecules or as photosensitizers to produce irreversible chemical or physico-chemical modifications on biological substrates, is being demonstrated to be a valuable method of investigating the interactions underlying a variety of phenomena. In fact, all possible primary steps in a photosensitized biological system are phenomena that may occur during the chromophore S1 lifetime and act as quenching mechanisms of the S1 state. Thus they can be identified, and the relative importance of the corresponding transient species quantitatively determined, with suitable techniques of time resolved fluorescence spectroscopy. The examples discussed in this paper concern both tumor photosensitizing drugs, such as anthracyclines and porphyrins, and skin sensitizers (e.g. furocoumarins). PMID- 2217553 TI - The use of fluorescent probes in immunochemistry. AB - The limitations and advantages of particular dyes for labelling proteins and other biological materials are discussed. Methods available for conjugating dyes to proteins are outlined. Following a discussion of double labelling methods the use of photoactivatable fluorochromes and time resolved fluorescence methodologies are outlined. The reasons for the photoinstability of some fluorochromes are discussed and methods for overcoming the problem are described. PMID- 2217551 TI - Characterization of RAD4 gene required for ultraviolet-induced excision repair of Saccharomyces cerevisiae propagated in Escherichia coli without inactivation. AB - The previously isolated RAD4 gene designated as pPC1 from the genomic library of Saccharomyces cerevisiae (Yoon et al., 1985, Korean J. Genetics 7, 97-104) appeared to propagate in Escherichia coli and yet retained its complementing activity to rad4 mutants without inactivation. The subcloned RAD4 gene was found to be localized within a 2.5 kb DNA fragment flanking Bg1II and BamHI sites in the insert DNA, and was shown to have the same restriction map as a yeast chromosomal DNA, as determined by Southern hybridization. Tetrad analysis and pulse-field chromosome mapping have revealed that the cloned RAD4 gene can be mapped and integrated into the yeast chromosome V, the actual site of this gene. DNA-tRNA hybridization has shown that the isolated RAD4 gene did not contain a suppressor tRNA gene. These results have indicated that the pPC1 is a functional RAD4 gene playing a unique role involved in the nucleotide excision repair of yeast without any genetic change during amplification in E. coli. PMID- 2217554 TI - Photosensitized processes in vivo: proposed phototherapeutic applications. AB - The use of photosensitizing dyes having intense absorption bands in the 600-900 nm spectral interval opens up new prospects in the field of photochemotherapy, because it allows the illumination of relatively large tissue volumes with no significant damage to photosensitizer-free tissues. Special interest is currently focused on the photodynamic therapy of solid tumors, because of the property of several dyes with a macrocyclic chemical structure (porphyrins, chlorins, phthalocyanines, xanthenes) to accumulate in significant amounts and be retained for prolonged periods of time by neoplastic lesions. Strategies are being developed for enhancing the selectivity of tumor targeting by photosensitizers through the exploitation of functional or biochemical differences between normal and malignant cells. PMID- 2217555 TI - Morphology, physiology, and molecular biology of renin secretion. PMID- 2217556 TI - Micromechanical foundations of pulmonary elasticity. PMID- 2217557 TI - Facilitated diffusion of glucose. PMID- 2217558 TI - Developmental mechanisms underlying pathology of arteries. AB - This review tries to provide a general, and very speculative, view of growth control mechanisms that may be common to the development of blood vessels and to pathological processes including cell proliferation. From a developmental point of view, vascular growth is most likely to include local autocrine or paracrine mechanisms that permit the two cells of the vessel wall to grow, organize into the characteristic tubular and layered structures of the vessel wall, and eventually achieve a return to quiescence. The "real" mechanisms controlling growth in vivo are difficult to ascertain from studies in culture. For example, a large list of angiogenesis molecules must be able to generate endothelial replication, but in culture many of these molecules are inhibitory for each endothelial replication. Similarly, in culture, we have a long list of smooth muscle mitogens, but none of these have as of yet been proven to control smooth muscle growth in vivo. Endothelial growth control has been attributed to the presence of membrane molecules able to inhibit endothelial replication and to the actions of soluble growth factors and their receptors. Unfortunately for the former hypothesis we still lack specific molecules with the properties of contact inhibition of replication. The data discussed here, however, suggest that modulation of expression or function of cell-cell adhesive molecules could be critical both to morphogenic changes and to mitogenesis by release of cells from cell-cell contact. Moreover, our data and data from other laboratories suggest that angiogenic factors, including the HBGFs and TGF-beta, may function in angiogenesis by altering cell-cell and cell-cell substrate interactions rather than via a primary effect on cell replication. This view of angiogenesis is consistent with the absence of a mitogenic effect of some angiogenic factors. Although endothelial cell replication is obviously necessary to angiogenesis, the lack of mitogenic effect of some factors suggests a need for a more general explanation of the actions of angiogenic factors. Endothelial injury may be interrelated with smooth muscle growth. The simplest possibility is that a failure of the endothelial cell barrier function, due either to denudation or an increase in adhesivity for leukocytes, would permit access of platelets or leukocytes to the vessel wall. These extrinsic cells, in turn, would stimulate smooth muscle cell replication by release of growth factors. The second possibility is that the endothelial cell may itself release growth factors into the vessel wall.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2217561 TI - Caring is risky. PMID- 2217559 TI - Structure and function of small arteries. AB - The small arteries (prearteriolar vessels with lumen diameter less than approximately 500 microns) contribute importantly to and participate actively in the regulation of the peripheral resistance. New techniques, building on the classic histological and hemodynamic techniques, have enabled detailed in vitro investigation of small arteries. At present, research in small arteries is in its infancy, and our understanding of the heterogeneity of small arteries within vascular beds, between vascular beds, and between species is extremely limited. This review attempts to describe the current status of the field. New techniques, based primarily on a wire myograph (where the vessels are mounted as ring preparations) and a pressure myograph (where vessels are cannulated and pressure lumen relations are determined), have allowed in vitro investigations of small arteries. The more physiological arrangement of the pressure myograph allows, for example, investigation of the vasoconstrictor response to raised intravascular pressure (the Bayliss response), whereas the less-sophisticated wire myograph is similar to use and may be more useful in certain situations where particular mechanisms are being investigated. Both techniques allow simultaneous measurements of vessel tone and a variety of parameters (e.g., membrane potential and intracellular ion activities) and thus allow precise determination of the relation between small artery structure and function. The vessels appear to remain fully viable with regard to the contractility of their smooth muscle cells as well as to the function of their perivascular nerves and their endothelium. The evidence suggests that the monovalent transport mechanisms in the plasma membrane, in particular potassium channels, play an important role in the determination of the membrane potential in small arteries, although the relation is more complex than indicated by the Goldman equation. Confirmation of these findings requires, however, simultaneous determinations of ion transport and vascular tone under conditions where vessels are subjected to mechanical loading. The membrane potential, through its effect on potential-dependent calcium channels, plays an important role in the determination of vascular tone. With regard to calcium homeostasis, current knowledge is hampered by the lack of direct measurements of the relation between cytoplasmic calcium and vascular tone. The evidence, however, suggests that besides potential-dependent calcium channels, receptor-operated calcium channels are present in the plasma membrane, although this still requires confirmation. The role of the sarcoplasmic reticulum is not clarified.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2217562 TI - Trust is strengthened through commitment. PMID- 2217560 TI - Microlymphatics and lymph flow. AB - A careful review of several different organs shows that with the information available today the beginnings of the microlymphatics in the tissue consist of endothelialized tubes only. Lymphatic smooth muscle within the collecting lymphatics appears further downstream, in some organs only outside the parenchyma. This particular anatomic picture has been observed in many different mammalian organs and in humans. The nonmuscular, so-called initial, lymphatics are the site of interstitial fluid absorption that requires only small and transient pressure gradients from the interstitium into the initial lymphatics. A fundamental question concerns the mechanism that causes expansion and compression of the initial lymphatics. I presented several realistic proposals based on information currently on hand relevant to the tissue surrounding the initial lymphatics. To achieve a continuous lymphatic output, periodic (time variant) tissue stresses need to be applied. They include arterial pressure pulsations; arteriolar vasomotion; intestinal smooth muscle contractions and motilities; skeletal muscle contraction; skin tension; and external compression, such as during walking, running, or massage, respiration, bronchiole constriction, periodic tension in tendon, contraction and relaxation of the diaphragm, tension in the pleural space during respiration, and contractions of the heart. The nonmuscular initial lymphatic system drains into a set of contractile collecting lymphatics, which by way of intrinsic smooth muscle propel lymph fluid. The exact transition between noncontractile and contractile lymphatics has been established only in a limited number of organs and requires further exploration. Retrograde flow of lymph fluid is prevented by valves. There are the usual macroscopic bileaflet valves in the initial and collecting lymphatics and also microscopic lymphatic endothelial valves on the wall of the initial lymphatics. The latter appear to prevent convective reflow into the interstitium during lymphatic compression. Many of the lymph pump mechanisms have been proposed in the past, and most authors agree that these mechanisms influence lymph flow. However, the decisive experiments have not been carried out to establish to what degree these mechanisms are sufficient to explain lymph flow rates in vivo. Because individual organs have different extrinsic pumps at the level of the initial lymphatics, future experiments need to be designed such that each pump mechanism is examined individually so as to make it possible to evaluate the additive effect on the resultant whole organ lymph flow.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2217564 TI - Tissue expansion for the treatment of keloids. PMID- 2217565 TI - Medicare payment reforms: implications for the nursing specialties. PMID- 2217563 TI - Lasers in plastic surgery: applications and nursing interventions. PMID- 2217566 TI - Neck masses. PMID- 2217568 TI - Case study: subcutaneous mastectomy. Part I. PMID- 2217567 TI - False negative HIV tests--who should be protected? PMID- 2217569 TI - "Patient education" series debuts in this issue. PMID- 2217570 TI - Physical map and properties of a 90-MDa plasmid of Azospirillum brasilense Sp7. AB - Homology was previously detected between the DNA restriction fragments containing Rhizobium meliloti nodulation genes and the 90-MDa plasmid, p90, of Azospirillum brasilense Sp7. Two DNA loci from Sp7 genome that complement mutations in the exopolysaccharide synthesis genes, exoB and exoC, of R. meliloti were also shown to be present on the plasmid. A more detailed characterization of the plasmid was undertaken to establish its physical map and to localize the nod homologies and other specific regions. Six loci were mapped, the region homologous to the nodulation genes, nodPQ, of R. meliloti, the exoB and exoC mutation-correcting loci, a locus for Ap resistance, a bla homology region different from the Ap resistance locus, and a region necessary for the maintenance of p90 as an independent replicon. Mobilization into Agrobacterium tumefaciens of p90-Tn5-Mob was obtained at a frequency of 10(-4), with the plasmid helper pJB3JI. Self transfer of p90 was not demonstrated. Fragments of p90 hybridized with a plasmid of 90 MDa present in most A. brasilense and some A. lipoferum strains, suggesting a plasmid family in Azospirillum. PMID- 2217571 TI - Behavior of the hybrid plasmid pNSW301 in Zymomonas mobilis grown in continuous culture. AB - The stability of the plasmid pNSW301 which was formed by cointegration of the Inc W R plasmid Sa and the 14.5-kb pNSW1 plasmid of Zymomonas mobilis ZM6100 was investigated in ZM6100(pNSW301) grown in continuous culture without antibiotic selection. The cointegrate plasmid, pNSW301, was found to be structurally unstable and a total reduction in the size of pNSW301 of approximately 21 kb occurred during growth in continuous culture. Following a systematic study, a number of deletion derivatives of pNSW301 were isolated and used to transform Escherichia coli HB101, with the exception of pNSW312. The plasmid pNSW312 was 100% stable in ZM6100(pNSW312) in continuous culture but was unable to replicate in E. coli. PMID- 2217572 TI - Isolation of the replication DNA region from a Rhizobium plasmid and examination of its potential as a replicon for Rhizobiaceae cloning vectors. AB - The DNA region essential for replication and stability of a native plasmid (pTM5) from Rhizobium sp. (Hedysarum) has been identified and isolated within a 5.4-kb PstI restriction fragment. The isolation of this region was accomplished by cloning endonuclease-restricted pTM5 DNA into a ColE1-type replicon and selecting the recombinant plasmids containing the pTM5 replicator (pTM5 derivative plasmids) by their ability to replicate in Rhizobium. DNA homology studies revealed that pTM5-like replicons are present in cryptic plasmids from some Rhizobium sp. (Hedysarum) strains but not in plasmids from strains of other Rhizobium species or Agrobacterium tumefaciens. The pTM5 derivative plasmids were able to replicate in Escherichia coli and A. tumefaciens and in a wide range of Rhizobium species. On the basis of stability assays in the absence of antibiotic selective pressure, the pTM5 derivative plasmids were shown to be highly stable in both free-living and symbiotic cells of Rhizobium sp. (Hedysarum). The stability of these plasmids in other species of Rhizobium and in A. tumefaciens varied depending on the host and on the plasmid. Most pTM5 derivative plasmids tested showed significantly higher symbiotic stability than RK2 derivative plasmids pRK290 and pAL618 in Rhizobium sp. (Hedysarum), R. meliloti, and R. leguminosarum by. phaseoli. Consequently, we consider that the constructed pTM5 derivative plasmids are potentially useful as cloning vectors for Rhizobiaceae. PMID- 2217573 TI - Cloning of the determinants for microcin D93 production and analysis of three different D-type microcin plasmids. AB - Three different microcin plasmids coding for D-type microcins were analyzed. Two of the plasmids (pMccD93 and pCP101) were small, multicopy plasmids and were closely related. The third plasmid (pCP106) was a conjugative, antibiotic multiresistance plasmid. Although plasmids pCP101 and pCP106 were previously classified as A-type microcin plasmids, we have determined that they are, in fact, D type. Furthermore, the determinants for microcin D93 production were cloned from plasmid pMccD93, and a DNA probe for the region implicated in the synthesis of microcin was obtained. This probe hybridized to plasmid C from Escherichia coli strain V517, indicating that this plasmid might be involved in the synthesis of a D-type microcin. The characteristics of replication of plasmid pCP106 were analyzed and appeared to be similar to those of ColEl plasmids, although pCP106 is a conjugative single-copy plasmid. PMID- 2217574 TI - Nocardioform arsenic resistance plasmids and construction of Rhodococcus cloning vectors. AB - One of a number of large nocardioform plasmids previously obtained by a primarily genetic approach was reduced in size to about approximately 11 kb. This smaller plasmid possessed determinants for resistance to sodium arsenate and sodium arsenite, as well as immunity to nocardiophage Q4. It was joined to an Escherichia coli-positive selection vector constructed by M. Zabeau and colleagues, which had the EcoR1 endonuclease gene placed under the control of the PR promoter of lambda as well as a bla determinant. The resulting shuttle vector of about 14.6 kb was maintained in E. coli and in several strains of Rhodococcus. The vector was efficient in cloning DNA without prior alkaline phosphatase treatment, as a result of the presence of the positive selection function. This function was not significantly expressed in Rhodococcus, and the presence of the nocardioform resistance determinants led to no increase in arsenate or arsenite resistance in E. coli. The presence of the bla gene resulted in an increase of about threefold in ampicillin resistance in Rhodococcus strains. PMID- 2217575 TI - Physical and genetic analyses of IncI2 plasmid R721: evidence for the presence of shufflon. AB - A physical map of the 75.1-kb IncI2 plasmid R721 was constructed by using 15 restriction enzymes, and the regions of several genetic determinants including the origins of replication and of conjugal DNA transfer were located on the physical map. It was found that R721 bears a DNA region which undergoes DNA rearrangement similar to the shufflon of R64. PMID- 2217576 TI - Insertion of plasmids into the chromosome of Streptomyces griseofuscus. AB - The results demonstrate a general method for randomly integrating plasmids into the genome by a single crossover between a cloned DNA fragment and homologous DNA in the chromosome. The integrated plasmid is flanked by directly repeated copies of the cloned homologous DNA sequence. Two protocols, "replica plating" and "liquid transfer," yielded strains with integrated plasmids. PMID- 2217577 TI - The Le Fort III advancement osteotomy in the child under 7 years of age. AB - This is a longitudinal study of 12 patients with craniofacial synostosis syndromes (Crouzon's, Apert's, Pfeiffer's) who underwent Le Fort III advancement under the age of 7 years (average age 5.1 years, range 4.0 to 6.7 years). The average follow-up was 5.0 years and included clinical, dental, and cephalometric examinations according to a prescribed protocol. The study demonstrated that the procedure could be safely performed in the younger child with an acceptable level of morbidity. There was a remarkable degree of postoperative stability of the maxillary segment. However, although vertical (inferior) growth or movement of the midfacial segment was demonstrated, there was minimal, if any, anterior or horizontal growth. Any occlusal disharmony developing during the period of follow up could be attributed to anticipated mandibular development and could be corrected by orthognathic surgery. The roles of surgical overcorrection and anterior-pull headgear therapy after release of intermaxillary fixation are also discussed. The Le Fort III osteotomy is justifiably indicated during early childhood for psychological and physiologic reasons. PMID- 2217579 TI - Surgical correction of Tessier number 8 cleft. AB - The number 8 Tessier cleft can be a discrete horizontal shadow at the level of the lateral canthus of the palpebral fissure or a true coloboma with absence of the commissure between the upper and lower eyelids. A surgical technique, which has been used in eight patients, is described to correct this congenital defect. Four flaps are created and transposed as two Z-plasties. The lateral canthal ligament is fixed to the lateral orbital rim, and the orbicularis muscle is interdigitated to restore its continuity. This procedure reconstructs the depth of the conjunctival fornix, provides proper form and length to the palpebral fissure, and restores continuity and an anatomic angle to the malformed canthus. PMID- 2217578 TI - Geometrical planning for the correction of orbital hypertelorism. AB - Orbital hypertelorism may be associated with a variety of deformities affecting several elements of the craniofacial skeleton. Shortness of the central portion of the face represented by a wide, short nose and anterior open bite is frequently combined with the exaggerated interorbital distance. With the mobilization of the two halves of the face it is possible to approximate the orbits, simultaneously elongating the center of the face and normalizing the maxillary alveolar ridge. A technique is described to plan the operation geometrically in order to predict accurately the skeletal correction, the change of the inclination of the eye slant, and the modification of the axis of the teeth. PMID- 2217581 TI - One-stage closure of the entire primary palate. AB - Timing of the closure of the anterior palate and alveolus is a subject of debate. Late repair of this defect is complicated by high fistula formation and subjects the patient to the problems of palate fistula for extended periods of time. We have utilized a single procedure performed when the child is 3 months of age that completely closes the anterior hard palate and alveolus along with the cleft lip. Our series consisted of 61 consecutive patients with unilateral clefts of the primary and secondary palate. Mucosal turnover flaps from the vomer along with lateral nasal mucosal flaps provide the nasal lining. A buccal sulcus flap with a Veau flap completes the oral repair. Ninety-five percent (58 of 61) of the patients had complete and stable closure of their anterior palate and alveolus after 1 year. The incidence of fistula formation in our series (3 of 61) is much lower than that reported with the utilization of other protocols. Excellent exposure of the anterior palate and alveolar defect during lip repair, early restoration of anatomic relationships, establishment of a good nostril floor and sill, and very low fistula formation are among the benefits of this procedure. The increase in operative time is considered minimal in light of aforementioned advantages. PMID- 2217580 TI - Histologic investigation of vascular malformations of the face after transarterial embolization with ethibloc and other agents. AB - Twenty-one vascular malformations located in the facial area, 11 high-flow arteriovenous malformations and 10 slow-flow malformations, underwent combined treatment by embolization and later surgery. Embolization was performed simultaneously with superselective angiography of the branches of the external carotid artery. The new biodegradable fibrosing agent Ethibloc was used in 16 cases. Histologic examination of the surgical specimens confirmed the good target orientation by the transarterial injection of Ethibloc. Limitations of this technique are discussed. The agent proved to have thrombogenic and fibrogenic properties. Some of the vascular walls degenerated and ruptured following the embolization, but there were no instances of necrosis of interstitial tissue or skin. Embolization treatment of vascular malformations of the face was not curative, but it facilitated subsequent surgery in all examined cases. PMID- 2217582 TI - Retro-orbicularis oculus fat (ROOF) resection in aesthetic blepharoplasty: a 6 year study in 63 patients. AB - Sixty-three nonconsecutive patients have undergone resection of the retro orbicularis oculus fat (ROOF) in conjunction with aesthetic blepharoplasty. In these patients, a consistent and useful ability to soften and flatten heaviness and bulkiness in the lateral upper orbital region was seen. Two patients developed postoperative hematoma, and two different patients had transient dry eye symptoms following blepharoplasty. Twenty percent of patients had a transient degree of numbness in the lateral supraorbital nerve region, and all patients noted some transient numbness over the lateral upper brow region. No patient demonstrated significant paralysis of the orbicularis oculus or corrugator muscle. From this experience, retro-orbicularis oculus fat resection would appear to be a useful adjunct to standard blepharoplasty techniques in selected patients. PMID- 2217583 TI - The submuscular aponeurotic system (SMAS): a histologic and comparative anatomy evaluation. AB - The submuscular aponeurotic system (SMAS) has been steeped in controversy. The goal of our anatomic study was to further clarify the existence of the SMAS. With an operating microscope, we performed dissections in 10 fresh cadaver heads (20 hemiheads) exposing the SMAS through a face lift incision. Through the operating microscope we were able to identify the SMAS and its relationship to other anatomic structures. Full-thickness longitudinal sections were obtained for routine histologic studies along various surgically relevant regions of the SMAS. In addition, dissections were accomplished with the operating microscope on 12 rhesus monkey fetuses ranging in age from a few weeks to 8 months. Data obtained from the fresh cadaver microdissections, topographic histology, and comparative anatomy revealed the presence of the SMAS as a distinct fibromuscular layer composed of the platysma muscle, parotid fascia, and fibromuscular layer covering the cheek. PMID- 2217585 TI - Augmentation mammaplasty by means of the transrectus route. AB - A new operative technique has been developed for augmentation mammaplasty. Through an inframammary incision, the anterior rectus sheath is entered, and the pocket is dissected in an entirely submuscular plane. We have performed this procedure in 112 patients to date. Complications have been few. The capsular contracture rate in 90 patients followed for greater than 1 year is 7 percent. The inframammary crease can be lowered using this technique, making mastopexy unnecessary in most patients with moderate ptosis. PMID- 2217584 TI - Long-term survival after chest-wall reconstruction with musculocutaneous flaps. AB - Reconstruction of chest-wall defects with musculocutaneous flaps permits resection of advanced chest-wall tumors and of tissues severely damaged by radiotherapy in patients who in a previous era were not surgically treatable. To determine the long-term outcome from this surgery, the records of 96 patients who had undergone chest-wall resection with musculocutaneous flap reconstruction were reviewed. Median survival for the entire group was 20.5 months, but a more accurate prediction of outcome could be obtained by dividing the patients into three groups. In group I, patients free of known malignancy and undergoing resection of radionecrotic tissues, median survival was 60.0 months. In group II, patients with resectable disease and free of tumor following surgery, median survival was 31.1 months. In group III, patients incompletely resected or known to have metastatic disease following surgery, median survival was only 12.5 months. Even in group III, however, some individuals achieved prolonged survival and lasting benefits from the surgery, so these data should not be used to exclude patients from undergoing necessary palliative procedures. PMID- 2217586 TI - Polyurethane foam-covered implants and capsular contracture: a laboratory investigation. AB - Experiments were conducted in rabbits comparing polyurethane foam-covered implants with otherwise identical smooth silicone gel implants. Using five objective methods of measurement of capsular contracture, no significant difference could be identified. The foam-covered implants consistently developed capsular contracture, although in most cases this was of mild degree and would not have been clinically significant. In the two foam-covered implants with hard contractures, there was no evidence of hematoma or separation of the foam. PMID- 2217587 TI - Evaluating breast parenchymal maldistribution with regard to mastopexy and augmentation mammaplasty. AB - Mammary parenchymal maldistribution or lower-pole hypoplasia, a first cousin of the tubular breast deformity, is a common condition complicating the selection of patients for retropectoral augmentation mammaplasty and/or mastopexy. The eccentric mammary parenchyma must be released from the pectoral fascia to obtain good results with augmentation mammaplasty and to minimize the necessity for mastopexy. PMID- 2217588 TI - Stretching skin: undermining is more important than intraoperative expansion. AB - The efficacy of intraoperative expansion in reducing the tension of wound closure was tested in young pigs. The young piglet as a model for studying human skin was characterized by finding a close similarity between the modulus of elasticity of young piglet skin and human abdominoplasty and mammaplasty skin (range 12.8 to 23.7 N/mm2 for piglet skin, 14.3 to 19 N/mm2 for human skin). The tension required to close a standardized wound was determined before undermining, after undermining, and finally after intraoperative expansion. These measurements were performed in 10 young pigs with an average weight of 11.5 kg. Undermining the wound edges resulted in a significant decrease in the force required to close the wounds (p less than 0.0001). Intraoperative expansion did not significantly decrease the tension. Previous work showing the importance of site and direction of pull on the tension for wound closure was confirmed in this study. Analysis of variance demonstrated that the tension required to close a standard wound is greater high on the pig's back than near the belly and near the shoulder as opposed to the hip for midflank wounds (p less than 0.0001). Increasing the extent of undermining from 62 to 136 cm2 significantly decreased the tension for wound closure (p less than 0.05). Further undermining did not result in a significant decrease in wound closure tension. In this model, intraoperative expansion offers no advantage over simple undermining. We suggest that the benefit reported by clinicians using intraoperative expansion may derive from an increase in the extent of undermining required to place expanders under the wound margins. PMID- 2217589 TI - Surgical augmentation of skin blood flow and viability in a pig musculocutaneous flap model. AB - A porcine rectus abdominis musculocutaneous (TRAM) flap model was designed and validated in nine pigs. This TRAM flap was based on the deep inferior epigastric (DIE) vessels with an 8 x 18 cm transverse skin paddle at the superior end of the rectus abdominis muscle. The model was subsequently used to test our hypothesis of surgical augmentation of flap viability by vascular territory expansion. Specifically, we observed that ligation of the superior epigastric (SE) vessels at 4, 7, 14, and 28 days (N = 6 to 8) prior to raising the TRAM flaps significantly increased (p less than 0.05) the length and area of the viable skin in the transverse skin paddles of the treatment flaps compared with the contralateral shammanipulated control flaps. This significant increase in skin viability was seen to be accompanied by a significant increase (p less than 0.05) in skin and muscle capillary blood flow in the treatment TRAM flaps compared with the controls (N = 9). The mechanism of vascular territory expansion is unclear. We postulate that hypoxia resulting from the ligation of the superior epigastric vessels prior to the flap surgery may play a role in the triggering of the deep inferior epigastric artery to take over some of the territory previously perfused by the superior epigastric artery. This would then increase the skin and muscle capillary blood flow in the transverse paddle when the TRAM flap was raised on the deep inferior epigastric vascular pedicle. PMID- 2217590 TI - Critical ischemia times and survival patterns of experimental pig flaps. AB - Previous work on critical ischemia time suggested (1) a greater susceptibility of myocutaneous flaps over skin flaps to the ischemia reperfusion injury and (2) that duration of ischemia may affect the survival area of a flap. Using a pig model, 55 animals were operated on and the critical ischemia times and survival patterns of the buttock skin (n = 85) and latissimus dorsi myocutaneous (n = 88) island flaps were determined after being submitted to 0, 2, 4, 6, 8, 10, 12, 14, and 16 hours of normothermic ischemia. The average critical ischemia times (CIT50) were determined to be 9 and 10 hours for the buttock skin and latissimus dorsi myocutaneous flaps, respectively. Percentage of total area surviving (%TAS) in those flaps which did survive was adversely affected by increases in the ischemic interval in both flap models. A statistically significant decrease in percentage of total area surviving was found after 6 and 8 hours of ischemia for the buttock skin and latissimus dorsi myocutaneous flaps, respectively. PMID- 2217591 TI - Flap failure after microvascular free-tissue transfer: the fate of a second attempt. AB - In most cases, the loss of a free-tissue transfer is a disaster for both the patient and the surgeon. Seven patients received a second microvascular free tissue transfer after loss of the first. The indications for free-tissue transfer included chronic osteomyelitis of the lower leg (four patients), acute traumatic defect of the leg (one patient), acute traumatic defect of the arm (one patient), and esophageal defect after surgical excision (one patient). In three patients, the interval between the first and second procedures was less than 2 weeks. The remaining four patients had their second free-tissue transfer performed 5 weeks to 21 months after the first. Six of the seven free flaps were successful. Two patients with venous obstruction occurring after the second free-tissue transfer were salvaged by reexploration. Partial loss of the flap was noted in one of these patients. It is concluded from this select group of patients that failure of a free-tissue transfer does not contraindicate a second microtissue transfer does not contraindicate a second microvascular free-tissue transfer. PMID- 2217592 TI - Comparison of lymphatic and venous interpositional autografts in experimental microsurgery of the canine lymphatics. AB - In mongrel dogs, 56 autologous lymphatic and vein grafts were interpositioned to bridge a defect in the femoral collecting lymphatics. In one group, 26 lymphatic autografts were interpositioned with good results. No obstruction was observed over 6 months. In another group, 20 venous autografts were interpositioned after irrigation with heparinized saline and another 10 autografts were interpositioned without irrigation. After 1 week, four irrigated grafts were partially occluded with a red thrombus; after 6 months, all grafts were totally occluded. In a third group, 15 lymphaticolymphatic anastomoses were enveloped by a silicone sheet to provoke prolonged devascularization. None of the vessels was patent. Anastomotic patency was inspected in vivo postoperatively. The specimens were studied with light microscopy and scanning and transmission electron microscopy. Prolonged devascularization damaged the endothelial cells. The results show that the lymphatic vessel autograft is the best choice for an interpositional autografting to bridge a defect in lymphatic vessels. PMID- 2217593 TI - No room at the trough: an epitaph for the eighties. PMID- 2217595 TI - Congenital lateral cleft palate: a new anomaly? AB - A case of atypical cleft palate abnormality that had not been identified before in a 9-year-old girl is presented. The cleft was localized laterally and in an oblique position at the soft palate. The patient had cleft palate repair. Finally, she had acceptable soft palate movements and speech. PMID- 2217594 TI - Intracerebral hematoma complicating split calvarial bone-graft harvesting. AB - A case is reported of an intracerebral hematoma following the harvest of split calvarial bone. Full recovery by the patient occurred. Complications following calvarial bone graft harvest are reviewed. Potential devastating complications warrant serious consideration of alternative sources of bone, especially in the purely elective surgical candidate. PMID- 2217596 TI - Contour correction of the vermilion of the upper lip by island flap of the lower lip. AB - A method is shown to correct contour defects of the upper lip vermilion by an island of vermilion of the lower lip. A muscle bundle of the orbicularis oris is used to carry the island. It is tunneled around the commissure to the upper lip defect. Three cases are shown. PMID- 2217597 TI - Recurrent anterior dislocation of the ulnar nerve at the cubital tunnel. AB - Recurrent anterior dislocation of the ulnar nerve at the cubital tunnel is reported in two patients. This was due to traumatic attenuation of the flexor carpi ulnaris retinaculum. The mechanism of injury in both patients was a fall with the shoulder abducted and the elbow acutely flexed. Both patients had relief of their neurologic symptoms following anterior submuscular transposition of the ulnar nerve. PMID- 2217598 TI - New treatment for frontal sinus hypertrophy. AB - A new treatment of frontal sinus hypertrophy is described. The anterior wall is removed, inverted, and attached again. The resulting depression is filled with bone dust. Details are discussed, and a case is presented. PMID- 2217599 TI - A trilaminar skin coverage technique for treatment of severe degloving injuries of the extremities and torso. AB - A 60 percent degloving injury involving the torso and lower extremities of an 8 year-old boy is described. Successful management employed the use of a new trilaminar skin coverage technique. With the avulsed flap still attached to its bed, a 0.14-inch split-thickness graft of epithelium and superficial dermis is raised with a power-driven dermatome. From the same harvest site, one level deeper, a second layer consisting of split-thickness dermis (0.14 inch) is taken. Both the first and second layers are meshed and expanded. The remaining degloved flap is excised and, on a sterile bench, defatted to produce a third layer of deep dermis. In our case, this third layer was ultimately lost, but it functioned well as a temporary biologic dressing. Depending on donor-site morbidity, other potential applications of this method (i.e., major burn injuries) may be feasible. PMID- 2217601 TI - In defense of intrauterine repair of cleft lip. PMID- 2217600 TI - Historical studies: should you believe the results? PMID- 2217602 TI - Internal fixation of malar fracture. PMID- 2217603 TI - Definitive diagnosis of breast implant rupture by ultrasonography. PMID- 2217604 TI - An aid for interosseous wiring in mandibular fractures. PMID- 2217605 TI - Keloids and hypertrophic scars. PMID- 2217606 TI - The "zipper" stitch for intradermal closure. PMID- 2217607 TI - Treating the short nose. PMID- 2217608 TI - Unaesthetic horizontal lip incisions. PMID- 2217609 TI - The functional pectoralis major musculocutaneous island flap for head and neck reconstruction. PMID- 2217610 TI - Total implant tracking system. PMID- 2217611 TI - Decreasing mobility of cheek implants. PMID- 2217612 TI - Treatment of capsular contracture around retromammary implant. PMID- 2217613 TI - The omentum as coverage in mediastinitis. PMID- 2217614 TI - Nasal tip augmentation with cartilage graft in aesthetic rhinoplasty: an accurate placement. PMID- 2217615 TI - The "clean" wound. PMID- 2217616 TI - Keep an eye open for glaucoma. PMID- 2217617 TI - [Inflammation of the bronchial mucosa as the basis for airway hyperreactivity]. AB - The mechanisms that are involved in asthma pathogenesis have been the subject of intensive research in the last few years. Numerous studies have shown involvement of inflammatory cells and their mediators in the damage of the bronchi. Inflammation leads to morphological changes in the bronchial wall: damage of the epithelium, increased deposition of collagen beneath the epithelial basement membrane, oedema and infiltration of the mucosa with inflammatory cells, hyperplasia of the mucous glands and hypertrophy of the bronchial smooth muscles. The relationship between inflammation and bronchial hyperresponsiveness is complex and remains unclear. This review article will encompass the current understanding of inflammatory mechanisms in asthma and their association with morphological changes in the airways and the syndrome of bronchial hyperresponsiveness. PMID- 2217618 TI - [Results of bronchodilation tests in workers exposed to occupation respiratory noxae]. AB - In order to detect and assess the spastic components in airway obstruction of workers exposed to inhalation of different nonorganic and organic dusts, 129 workers of metal industry and 135 workers of textile industry were examined. The workers of metal industry were exposed to the following respiratory noxa: toluol, paint aerosol, mineral dusts (SiO2 up to 10%), asbestos dust, metalic dust and several chemical noxa (acetone, CO, CO2, ZnO, FeO and petrol). In textile industry the dust of vegetal origin was detected with unfavourable micro climatic factors. In both groups the similar results were found with very high percent of spastic components. After bronhodilatatory testing the most significant differences were found in the following tests: Raw, FMF25-75, FEF75-85, components. Several significant spastic components were present in workers of metal industry which are due to the polluted working area. In relation to the mean values of tests, the greatest number of different results was found in FEF75 85 and Raw tests. It is suggested that the workers with these results should be tested as well. PMID- 2217619 TI - [Evidence of the harmful effects of eosinophils in bronchial asthma]. AB - Fifteen asthmatic patients were prospectively selected. If they had more than 450 eosinophils in peripheral blood on admission to hospital treatment and if before BAL had been performed they were not treated by corticosteroids. No associated disease was found which could cause the increased number of eosinophils in peripheral blood except bronchial asthma. BAL was performed when the subjects tested had no dyspnea, usually 1-3 days after the hospital admission. In contrast to blood eosinophilia, increase of eosinophils number in BAL was found to correlate to impairment of clinically measured parameters such as: ventilation level of blood gases and duration of hospitalisation. On the contrary there was no correlation between the level of blood eosinophilia and gas disturbance and duration of hospitalisation. Eosinophilic proteins (MBP, ECP, EPX, EPO) are not the only that harmfully effect the lung cells in the asthmatic attack but the fact that their level in lavage fluid correlates to eosinophilia degree in BAL is evident so the correlation between the number of eosinophils in BAL and impairment of clinically measured parameters is clear. PMID- 2217620 TI - [The role of bronchoscopy with a flexible bronchoscope in the diagnosis of pulmonary tuberculosis]. AB - Bronchoscopy with flexible bronchoscope has been proved as a useful method that has been applied also in the diagnostics of pulmonary tuberculosis during the recent years. In order to evaluate its role and use at the Institute for Diseases of the Chest and Tuberculosis Golnik documentation of 51 patients treated during 1985 and 1986 was surveyed. Prior to the examination from all patients the sputum on Mycobacterium tuberculosis was obtained at least three times and it was negative. Aspirations were obtained from 40 patients and the diagnosis was confirmed in 21 patients by recovery from tubercle bacilli specimens (52.5%). Transbronchial biopsy was performed in 34 patients and it was positive in 27 (79.4%), out of them in 7 patients the biopsy sample of the lungs was bacteriologically (38.9%) and in 23 patients histologically positive (67.6%). By bronchoscopy with flexible bronchoscope the final diagnosis was confirmed in 40 patients (78.4%). Bronchoscopy with flexible bronchoscope as well as transbronchial biopsy have proved to be a successful method in the diagnostics of active pulmonary tuberculosis. It should be used in patients in whom the sputum smear for acid fast bacilli were frequently negative yet there is a suspicion of pulmonary tuberculosis. PMID- 2217621 TI - [A computer program for the interpretation of the acid-base status and respiratory gases]. AB - A computer program for analysing the parameters of the acid-base status and respiratory gases has been designed. The program separates cases which are included into classical picture of certain respiratory, metabolic and mixed disorders. Out of a test series of 200 findings, 93% findings have been accurately interpreted. The program is written in BASIC, translated into machine code and occupies about 25 Kbyte computer memory. The main parts of the program use commands which do not favorize any version of BASIC increasing the program portability to other systems. The classification of respiratory gases and acid base status was based on the already known facts. PMID- 2217622 TI - [Analysis of hospitalized tuberculosis patients at the Institute for Pulmonary Diseases and Tuberculosis in Belgrade, Serbia during 1988]. AB - The report presents the analysis of TB patients treated at the Institute for lung diseases and tuberculosis of SR of Serbia during 1988--a total of 567 or 10.18% of discharged patients. There were 77% TB patients from Belgrade and 23% from the province. Tuberculosis retains the characteristics of a social disease with a morbidity peak in the fourth decade of age. There were 93% of cases discovered due to disease symptoms. In 82% of patients it was a case of newly discovered specific process, 7.5% had a recurrent disease and 10.5% of patients had a chronic form of the disease. The patients had almost all forms of the specific process: primary tuberculosis 0.35%, postprimary phthisis 84.4%, specific pleuritis 10.6%, tuberculom 1.9%, miliary tuberculosis 1.8%, lymphoglandular tuberculosis 0.9%, while 1.4% had extrathoracic specific lesions associated with pulmonary lesions. Cavernous tuberculosis was observed in 89% of TB patients and extensive phthisis in 14% of cases. Atypical forms of parenchymal specific process were observed in 12% patients. Bacteriological or histological confirmation of tuberculosis existed for 82%. In 13% of patients treatment lasted longer than 3 months. Six or 1% of patients died due to pulmonary tuberculosis. PMID- 2217624 TI - [Modulation of nonspecific bronchial hyperreactivity]. AB - Nonspecific bronchial hyperresponsiveness (NBHR) is a typical characteristic of asthmatic patients. The impairment of NBHR is due to the airway inflammations caused by the viruses, irritants from the air and especially by specific allergens from natural and working environment. NBHR is diminished by elimination of inflammatory triggers as well as by antiinflammatory measures, the most important being inhalatory glucocorticoids which should be administered for long term period in order to achieve the successful decrease of NBHR. PMID- 2217623 TI - [The role bronchial circulation in the etiopathogenesis of increased bronchial reactivity]. AB - The relationship between pathoanatomical changes in bronchial arteries and occurrence of chronic obstructive bronchitis (COB) and bronchial asthma (BA) was studied. Pathoanatomical changes in bronchial arteries were more frequently found in patients with COB and BA than in patients with other bronchopulmonary diseases, i.e. that bronchial circulation in patients with COB and BA is impaired. Due to these findings a theory of vasculary-metabolic explanation of pathogenesis of bronchial hyperresponsiveness is based on hypoperfusion and hypoxia of cellular structures in the bronchial wall. Hypoxia is supposed to be an endogenous change in the bronchial wall which causes bronchial hyperresponsiveness in various exogenous stimulants. PMID- 2217625 TI - [Nonspecific bronchial response in asymptomatic female smokers and nonsmokers]. AB - In 20 female smokers aged 21-58 yrs and 20 nonsmokers aged 22-48 yrs the effect of smoking on bronchial responsiveness was studied. In the study only those subjects were included who had no asthma and who had been without symptoms of any of the pulmonary disease and they had normal mean values of pulmonary function testing. In no subject the increase of bronchial responsiveness after maximal dose of 4 mg of metacholine was found. Since the statements in the literature are contradictory, further studies are necessary in order to clear up the effect of smoking on bronchial responsiveness. PMID- 2217626 TI - [Nonspecific bronchial reactivity in chronic bronchitis]. AB - In a segment of the population of Zagreb, Crnomerec, which was included in the epidemiological study on chronic bronchitis in Croatia (1969-1972-1982-1989) the values of ventilatory function and non-specific reactivity of airways were examined. The sample consisted of 34 women and 29 men with chronic bronchitis. The control group consisted of 34 men and 33 women--without cough. The average age was 58.6 (M) and 59.4 (F). Investigation of non-specific reactivity was carried out on the dosimeter apparatus APTA-Jaeger, Wurtzburg, W. Germany (by using histamine dehydrochloride (1-30 mg/ml dose) with expressed reactivity PC 40 Raw. PC 40 in subjects with chronic bronchitis amounted to 7.79 mg/ml in men and 8.89 mg/ml in women, which is significantly lower than the control group (14.04 M, 17.8 F). We did not determine significant difference between smokers and non smokers with regard to PC 40. By factor analysis in an orthogonal projection a link was noted between symptoms of chronic bronchitis, basic values of ventilatory function and PC 40. This is in agreement with known results. PMID- 2217628 TI - [Normal reactivity and hyperreactivity in the bronchi induced by respiratory irritants]. AB - The influence of age, sex, atopy, baseline spirometry and smoking habit on the presentation of airway reactivity (AR), and the prevalence of hyperreactive subjects was assessed in 176 normals and 143 subjects occupationally exposed to respiratory irritants. The study protocol comprised: a respiratory disease questionnaire, physical examination, skin prick-test to 13 common inhalant allergens, IgE level, spirometry. The nonspecific bronchoprovocation test (NBPT) was performed by the cumulative method proposed by Chai et al. (J Allergy Clin Immunol 1975; 56: 323-327). The results are expressed as PC20FEV1, PC25FEF50, PC25FEF25 and PC25FEF25/75. Age, sex, atopy, baseline spirometric values and smoking are not significantly correlated with indeces of AR. There are no hyperreactors among healthy subjects--according to the criterion: PC20FEV1 less than or equal to 2.17 micromoles of histamine. When the response was measured by flow-volume parameters, there were between 5.1% and 9% hyperreactors. In both examined groups AR has proved to be a highly variable feature. Among workers exposed to irritants there were 5.6% hyperreactors according to PC20FEV1 and between 11.1% and 13.9% when flow-volume parameters were applied. A significant correlation between AR and smoking habit of subjects occupationally exposed to irritants was not found. The level of AR when monitored by flow-volume parameters of subjects continuously exposed to irritants was found to be significantly lower than in normals. The chosen criterion separates successfully airway normo- from hyperreactives. It is a useful diagnostic method in occupational medicine. PMID- 2217627 TI - [Bronchial responsiveness in hops processing workers]. AB - In small group of workers (n = 17) who had been during their working process (storing and packing of hop) exposed to the inhalation of hop dust, the bronchial responsiveness with metacholine was studied according to cumulative method. Although 70% of examined subjects had clinically pronounced signs of bronchial irritation and 50% of them the signs of chronic bronchitis, the moderately increased bronchial responsiveness was found in only 12.5% of examined subjects (n = 2) which is--due to the data from the literature--the normal percent for healthy population. PMID- 2217629 TI - [The role of nonspecific nasal reactivity in the evaluation of induced bronchial hyperreactivity]. AB - The excitation of the irritant receptors in the upper respiratory tract may result in reflex bronchoconstriction. Does the raised reactivity of the nasal mucus membrane--the place of the first contact with respiratory irritants--play an important role in the expression of IBH? The level of NNR and the existence of relation between NNR and IBH have been assessed in 32 healthy subjects and 28 workers exposed to irritants with respiratory disorders. Nonspecific nasal provocation was performed by spraying of doubled concentrations of histamine solution in saline (0.03-16 mg/mL) in both nostrils in three minute intervals. The reaction was monitored by measurement of nasal peak inspiratory flow, nasal resistance, nasal forced expiratory volume in first second and nasal forced expiratory mid-flow. The level of NNR was expressed as provocation concentrations of histamine solution that produced significant change of all four measured parameters. Nonspecific bronchial provocation with histamine was performed by the modified method of Chai H. et al. The criterion for hyperreactivity was PC20FEV1 less than or equal to 8 mg/mL of histamine. There was statistically no significant correlation between NNR and IBH. PMID- 2217630 TI - [The intensity of bronchial hyperreactivity and the evolution of pulmonary function]. AB - The relationship between the degree of the bronchial hyperreactivity (BH) and evolution or prognosis of the bronchial asthma is determined in this prospective study. BH has been examined in 108 asthmatic children and after a long period of time (average 5.5 years), the pulmonary function (VC, FEV1, FEF25-75, Raw, IGV, RV/TLC, flow-volume curve was evaluated. Impaired pulmonary function was found not to correlate with the degree of the BH. It is concluded that the degree of the BH might predict the evolution and the prognosis of the bronchial asthma. PMID- 2217631 TI - [An apparatus for producing aerosols and depositing aerosols in the bronchial tree]. AB - The technical characteristics of most frequently used devices for the production of aerosol have been described together with their effect on deposition of aerosol in tracheobronchial system. However, there are many reasons to prefer jet nebulisers for everyday application. PMID- 2217632 TI - [Provocation agents for the evaluation of nonspecific bronchial responsiveness]. AB - Different pharmacological and nonpharmacological provocative agents used in the assessment of nonspecific bronchial responsiveness are presented. Their advantages and disadvantages as well as the attempt of the evaluation of their clinical applicability are discussed. The choice of provocative agent has still been the matter of personal judgement. PMID- 2217633 TI - [Etiopathogenic mechanisms of increased airway responsiveness]. AB - Views on mechanisms of increased airway responsiveness in patients with bronchial asthma and other respiratory tract are presented. The data have been divided into three parts: mucosal and submucosal changes, changes in airway regulations and effector cells. In the first part the etiopathological mechanisms of inflammatory processes in airways are explained. The second part views the neurogenic and other airway disorders (vagus reflex arc, local axon reflex, epithelial relaxing factor) while the third focuses on the receptor activity changes and cellular mechanisms known to cause airway hypersensitivity and hyperreactivity. PMID- 2217635 TI - [Use of the Astograph in nonspecific bronchoprovocation tests]. PMID- 2217634 TI - [Preventive measures in bronchial provocation tests]. AB - The author's own experiences together with the data from the literature are presented for application the bronchial provocation tests in the hospital and in out-patient's department for pulmonary disease. Contraindications and side effects in testing the nonspecific provocative agents are presented (metacholine, histamine, carbachol), in specific provocative agents as well as in exercise testing. These tests are relatively harmless if the preventive measures are taken into account. PMID- 2217636 TI - [Simultaneous recording of spirometric parameters and total respiratory resistance on the Astograph in nonspecific bronchial provocation tests using methacholine]. AB - Parallel study results of spirometric parameters (S.P.) FEV1, FEF50, FEF25 and total respiratory resistance (Rrs) measured by Astograph in nonspecific metacholine bronchoprovocation test were analyzed in 378 patients suspected of bronchial asthma. The patients were divided into 7 groups based on Astograph and S.P. instances criteria. Of 92 patients with positive test results, 91% met the set Astograph criterium; 72% met all three S.P. criteria, 1% one criterium and 12% failed to meet any of the S.P. criteria. It was noted that the patients met more the FEF50 and FEF25 criteria (87%) than FEV1 (73%). Also, there was no significant increase in respiratory resistance for those with a predominant reaction in small airways (9%). This fact points to the need of introducing appropriate complementary Astograph methods. PMID- 2217637 TI - [Simultaneous recording of nonspecific bronchial response using continuous measurement of total respiratory resistance and oxygen saturation of arterial blood]. AB - In 78 patients with bronchial asthma symptoms undergoing nonspecific bronchial response test with bronchoprovocation inhalation of progressively increased methacholine concentrations, total respiratory resistance (Rrs) and oxygen saturation (SaO2) of arterial blood were continually measured. An average Rrs increase was 153% when compared to the initial values and it correlated with SaO2 decrease (5.5% of the initial values). In 45 patients along with continual Rrs and SaO2 measurements, bronchoprovocation test and spirogram flow-volume curve were periodically done. Ten of these patients had no significant Rrs or FEV1 changes, but there was a considerable drop in FEF50, FEF25 and SaO2. These results, associated with dyspnea and physical pulmonary findings in the course of BPT, as well as history of patients with similar difficulties in every-day life and in work environment, point to the need of expanding diagnostic criteria for positive BPT and for patients who did not have Rrs increased double the initial values nor sufficient FEV1 20% drop. Spirometry and oximetry as complementary methods, increase Astograph sensitivity to methacholine test. Oximetry has an advantage of enabling continual SaO2 monitoring and increased patient's safety during the BPT. PMID- 2217638 TI - [Recommendations for the standardization of bronchial provocation tests using bronchoconstriction agents]. AB - The author is resuming part of the reports and discussions from the 26th Golnik symposium with the main topic "The measurement of nonspecific bronchial responsiveness." The indications for nonspecific bronhcoprovocation tests, different methods for production of aerosol and ways of inhalation of bronchoconstrictory agent are discussed. Further on the procedures for measurement of bronchial response, shorter one by inhalation of one dose and longer one by increased quantities of metacholine or histamine together with the interpretation of the results have been introduced as well. PMID- 2217640 TI - [Tuberculosis of the peripheral lymph nodes]. AB - An analysis of 2.414 fine needle aspiration specimens, obtained from peripheral lymph nodes, was done in 2.287 patients during the period from 1979 till the end of 1989. This investigation was performed at the Cytologic Laboratory of the Clinic for Lung Diseases "Jordanovac" in Zagreb. Totally, there were 150 (6.2%) aspirates which, cytomorphologically, appeared to have a granulomatous reaction with necrosis. Of 150 aspirates, Mycobacterium tuberculosis was found microscopically and/or by culture in 73 (3.02%) of them. The patients were less than 40 years of age in 63% of the cases. As to the localization, the highest rate of tuberculous lymph nodes (91.8%) was found in the neck and supraclavicular areas. PMID- 2217639 TI - [Legionnaires' disease in Yugoslavia (an epicritical review of patients)]. AB - A review of patients with Legionnaires' disease hospitalized in our Clinic from the first cases recorded in 1978 up to now has been given. The diagnosis was confirmed by indirect immunofluorescent method in 23 patients with pneumonia, using antigen and method of the Center for Disease Control Biological Products Division, Atlanta, Georgia, USA (Dr Wilkinson). Most of the patients (16) were sporadic cases and twice as less cases were from two epidemics (7). Two patients among sporadic cases developed a very severe form of the disease during the immunosuppressive therapy after kidney transplantation. Clinical, epidemiological and laboratory data of 10 patients hospitalized and treated during the last three years (1986-1988) were analyzed in details. Two thirds of these patients were above 40 years of age and the youngest one was 29 years old. Except the advanced age no other firm disposable factor was found in patients belonging to sporadic cases. In cases from epidemics the source of infection was probably water from water-pipes i.e. hotel devices (bathrooms, douches, drinking water, air conditioning units, water used in kitchen for cooking etc). All patients recovered after a longer symptomatic and antibiotic treatment. Erythromycin and rifampicin were applied the most frequently. In some patients treatment with chloramphenicol was effective. PMID- 2217641 TI - [Dressler's syndrome during radiotherapy in bronchial carcinoma]. AB - A case of Dressler's syndrome which has developed in a patient with bronchogenic carcinoma during radiotherapy is presented. Diagnosis is established according to symptomatology, clinical findings, chest X-ray, laboratory analysis and immunological findings. Existence of metastatic deposits in heart is excluded by the method of echocardiography. Short-term cardiologic therapy with antiflogistics is completely sufficient for maintaining the stability of "cardiologic status". PMID- 2217642 TI - [Pulmonary silicosis complicated by systemic vasculitis]. AB - A patient is described who had been--as a cutter of crystal--for 40 yrs exposed to the silica dust. At regular medical examinations at out-patients' department for pulmonary diseases first stage of pulmonary silicosis had been found and confirmed at the Institute for Occupational Health. Nine years after the retirement the clinical symptoms of febrility, cough, joint and muscular pains appeared together with the difficulties in swallowing and dyspnea even at minor physical activities. During the treatment the systemic vasculitis, probably visceral erythematodes, was established with satisfactory response to the corticosteroid therapy. PMID- 2217643 TI - [Primary mucociliary transport insufficiency]. AB - Case histories of 3 patients with primary mucociliary transport failure are described. Two of them had immotile cilia syndrome and one cystic fibrosis. In all three patients the same clinical picture was found and they had the same treatment, although the etiology of diseases was not the same. The treatment in two patients was not much successful since they had associated respiratory failure. PMID- 2217644 TI - [Pulmonary damage during amiodarone therapy]. AB - Pulmonary toxicity is a side effect associated with amiodarone therapy. Mechanism of lung injury remains speculative. Lung biopsy specimens reveal changes consistent with interstitial pneumonitis and alveolitis. Clinical picture is nonspecific. Diagnostic algorhythm for evaluation of patients receiving amiodarone together with a case report are discussed. PMID- 2217645 TI - [Neuron-specific enolase in pleural effusions of various etiologies]. AB - The concentration of neuron-specific enolase (NSE) was measured in the serum and pleural fluid of 42 patients with pleural effusions of different etiology. High levels (above 13.0 micrograms/l) of NSE in pleural fluid of 9 patients with malignant disease were observed (sensitivity 57%). However, pleural fluid NSE levels were also increased in 14 with non-malignant diseases (specificity 45%). Increased pleural fluid NSE activity is not specific for malignancy. PMID- 2217646 TI - [Analysis of immunocompetent cells in bronchoalveolar lavage in patients with sarcoidosis]. AB - Bronchoalveolar lavage through fiberoptic bronchoscope was performed in the right middle lobe or lingula of 8 patients with clinically and radiologically active sarcoidosis and 5 healthy persons. Pellet cells were analysed. Lymphocyte subsets were detected with monoclonal antibodies by fluorescent microscopy or flow cytometry (EPICS-C, Coulter). In patients with sarcoidosis lymphocyte proportion is elevated (29.88 +/- 4.32) as compared to healthy persons (5.2 +/- 3.4). We detected an increase of CD 3 lymphocytes (86.38 +/- 6.71) and CD 4 helper-inducer T lymphocytes compared to the total number of lymphocytes and, likewise, of the CD 4/CD 8 ratio--5.62 +/- 0.94. CD 8 suppressor-cytotoxic T lymphocytes are decreased (13.0 +/- 1.3 as compared to the healthy persons 22.0 +/- 3.84), which is a relative decrease because due to an increase of the total lymphocyte number, an increase of CD 8 T lymphocytes (3.85 +/- 0.41 as compared to the healthy persons 1.09 +/- 0.59) still exists, compared to the total number of pellet cells. PMID- 2217647 TI - [The effect of positive end-expiratory pressure on gas exchange and hemodynamics]. AB - The effects of positive end-expiratory pressure (PEEP) on arterial and mixed venous blood oxygenation as well as the effects on systemic and pulmonary circulation were studied in 15 patients with adult respiratory distress syndrome (ARDS) on mechanical ventilation. The measurements of arterial and mixed venous blood oxygen pressure (PaO2, PvO2), heart rate (HR), central venous pressure (CVP), pulmonary wedge pressure (WP), mean pulmonary arterial pressure (Ppa), mean systemic arterial pressure (Psa) and cardiac output (CO) were performed at 0, 5, 10 and 15 cm H2O PEEP. The positive effect of + 10 cm H2O on arterial oxygenation was found (PaO2 raised from 11.49 +/- 3.5 kPa to 13.3 +/- 3.3 kPa). Ppa raised too, from 23 +/- 7.6 mm Hg to 26 +/- 7 mm Hg. Psa and CO lowered at + 15 cm PEEP. Psa from 85 +/- 17 mm Hg to 73 +/- 17 mm Hg as well as CO from 8.22 +/- 1.1 l/min to 6.91 +/- 1.40 l/min. Authors conclude that PEEP can be accepted form of therapy in the treatment of refractory hypoxemia in patients with ARDS. Despite this beneficial effect, PEEP may adversely affect cardiovascular function. As with any therapy, the optimum PEEP "dose" should be tailored to each patient according to his needs and response. PMID- 2217648 TI - Interaction regulations used by schizophrenic and psychosomatic patients: studies on facial behavior in dyadic interactions. AB - This paper is part of an extensive research project that is trying to examine transference and countertransference processes objectively. We have used a methodology that describes and analyzes interactive behavior patterns observed between different groups of patients with psychic disturbances and their interaction partners, who are uninformed about their problems. Thus far, we have completed several studies centered around the question of whether it is possible to identify specific interaction strategies in groups of patients of different nosological categories. Related to this question was the investigation of the specificity of the response patterns of their interaction partners. The patients consisted of stutterers (stuttering openly or not, Krause 1982a), schizophrenics (Krause et al. 1989), and psychosomatic patients (Sanger-Alt et al. 1989). This line of inquiry has rather severe consequences for the research strategies, which have been described elsewhere (Krause et al. 1989). In this paper, we will present for the first time a synopsis of patterns of facial behavior observed in different groups of patients and their healthy partners, and in healthy subjects interacting with each other. PMID- 2217649 TI - Children of perpetrators of the Holocaust: working through one's own moral self. AB - The present study tests stages in the ability of some children of perpetrators of the Holocaust in Germany to work through emotional and moral issues regarding their fathers' perpetrating role during the Third Reich. The following questions are raised: Did they try to distance themselves by playing down the Holocaust and the moral meaning of their fathers' involvement in it? Did any children try to work through issues relating to their fathers' impaired morality? Did any children successfully reach the stage of integration? Fifty-seven persons were contacted by the author between September 1985 and June 1987, of whom 9 refused to be interviewed. Thirty interviewees were children whose fathers had taken an active part in the implementation of the euthanasia program, in the Einsatzgruppen, in the extermination camps or in related activities. The fathers of the remaining 18 interviewees were affiliated with SS units at times and in places where the atrocities took place, but what they actually did or did not do was not proven. In general, there was an almost total silencing of accounts of the extermination process in homes and schools. Acknowledgment, if any, of the atrocities appeared through accounts of trials and friends and in newspapers or, only recently, through the children's active searching. When children who learned what their father-perpetrator had done during the war also came to understand the moral implications, they usually experienced severe emotional conflict, which they had to confront on their own. Only a few succeeded in walking across a very narrow bridge to a working through of the related issues and emotions. The implications of the present analysis for future research on the prevention and outcomes of genocide are discussed. PMID- 2217650 TI - Psychiatric practice and the exigencies of the state: an ethnomedical view. AB - The purpose of this paper is to illustrate the powerful role that the state has in the practice of psychiatry in contemporary American society. An ethnomedical frame of reference is adopted, which is to say that psychiatric practice is looked at culturally and comparatively. In any society social and cultural characteristics condition and structure medical practice. In this sense, psychiatric practice provides an example to be analyzed in relation to other systems of medical practice. The ways in which the modern state, an omnipresent and compelling social structure, can intrude into the dynamics of psychiatric practice is illustrated by means of two case analyses. These draw attention to unique ethnomedical properties of psychiatric practice and to the potentially tragic effect that the state can have on its conduct. Analysis of the material presented is conducted against the background of information from the anthropological and social historical study of medicine and from medical practice in the Soviet Union. PMID- 2217651 TI - Violence and social structure on mental hospital wards. AB - Significant differences in the incidence and distribution of violent behavior in mental hospital wards exist even when the diagnoses and other characteristics of patients are essentially the same. In an effort to compare the structure and predictability provided by organizational and interpersonal processes in violent and peaceful wards, the senior author spent 38 months in participant-observation and interviewing on six wards in three state mental hospitals. Patterns emerged in ward social organization and staff behavior that were associated with varying levels of violence. These patterns reinforced previous observation that violence is a symptom of disorder not only in the biological and psychological field but also in the sociocultural field. Violence was more frequent and more extreme in wards in which staff functions were unclear, and in which events such as activities, meetings or staff-patient encounters were unpredictable. Violence was less frequent and less extreme in wards characterized by strong psychiatric leadership, clearly structured staff roles, and events that were standardized and predictable. Ward social organization characterized by standardized, repeated, predictable behavioral and procedural rituals provided stability and autonomy that supported efforts to develop a therapeutic milieu. PMID- 2217652 TI - The Numbers Man. PMID- 2217653 TI - Personality development in traditional Maori society and the impact of modernization. AB - This paper is an attempt to integrate the available research, clinical data and literary information concerning the developmental experiences of the New Zealand Maori. The Maori developmental pattern in the traditional society is compared with that of the Caucasian, mostly Anglo-Saxon, New Zealander (Pakeha), highlighting the contrasting elements while at the same time accommodating considerable overlap between the two postulated developmental patterns. The Maori personality development is seen as being characterized by an indulgent and permissive infancy, a withdrawal of this succorance during childhood, which is characterized by prominent peer-orientation, and a reintegration into adult society during adolescence with gradual maturation of social roles subsequently. The disruption of this pattern as a result of urbanization and Westernization is discussed, along with its adverse consequences. The recent initiatives by the Maori community to preserve the old traditions take the developmental issues into consideration, and although it is too early to judge their success or otherwise, they look quite promising. PMID- 2217654 TI - Cross-cultural views of self in the treatment of mental illness: disentangling the curative aspects of myth from the mythic aspects of cure. AB - This paper compares Eastern and Western concepts of self within the context of the healing process. I draw upon the work of Sudhir Kakar and Heinz Kohut to illustrate differences in how mental illness is expressed and treated in India and the United States. I propose that cultural variances in the way that illness is expressed and treated relate to differences in culturally determined "myths" of the self. In India, where Kakar lives and works, the self is conceived as fluid and interdependent; in the West, the self is conceived as more solid and autonomous. The therapeutic methods employed by the Western-trained psychoanalyst and psychotherapist make use of the Western myth of self. Likewise, in India the shaman heals in accordance with the myths available to him. No matter what our cultural background, such myths lend coherence to our experience and influence the way in which we solve our problems, including the problem of "mental illness." Finally, I suggest that these "myths" of self are not static and point out ways in which the Western myth of self is evolving. As these myths change, so do our methods of treating mental illness. PMID- 2217655 TI - Improving treatment for the severely mentally ill: implications of the decade long Italian psychiatric reform. AB - Recent reviews of the results of the important Italian Psychiatric Reform have been unusual in that they have ranged from very enthusiastic to very negative. No recent report has focused on extrapolating from the Italian experience the pluses and minuses that might be applicable to the U.S. system of delivery of mental health services so as to improve the care of the seriously mentally ill. In this paper I will summarize my observations and clinical research during 6 months in Italy, emphasizing what has not been reported by others; I will analyze the impact of the Italian changes on Italian practice and try to identify in a balanced way any inferences that can be drawn from the Italian experience that add to ideas now current in the United States about treatment of the severely mentally ill. PMID- 2217656 TI - Birth-cohort changes in the rates of mania. AB - Secular changes in the rates of mania have been reported in the relatives of affectively ill patients, and the present study is an independent replication of these findings in a large probability sample of a community. Data from the five U.S. sites of the National Institute of Mental Health's Epidemiologic Catchment Area study (ECA), a community survey of adults, are presented. A total of 17,827 respondents were divided into eight birth cohorts, each spanning a 10-year interval. Actuarial life-table analyses showed a greater cumulative risk of mania for white men and women from the three most recently born cohorts (i.e., those born after 1935). The Wilcoxon test for homogeneity indicated an overall significant difference by birth cohort. These findings in a community sample are consistent with those previously reported in relatives of affectively ill patients. The results support the hypothesis that birth cohort changes have occurred in the risk of mania and that the risk was greatest in the post-1935 cohorts. PMID- 2217657 TI - Risk factors in unipolar depression: II. Relation between proband REM latency and cognitions of relatives. AB - In an ongoing study of risk factors for depression in first-degree relatives of unipolar depressed probands, we have assessed cognitive variables (beliefs, attributional style, and moment-to-moment thinking) in relatives of reduced REM (rapid eye movement) latency unipolar probands, nonreduced REM latency unipolar probands, and normal control probands. Relatives of reduced REM latency probands had more negative cognitions; the effect of REM latency of the proband was independent of the effect of a personal history of depression in the relative. It appears that both biological and psychological factors can be identified as predictors for lifetime rates of depression and may be useful in identifying high risk individuals. PMID- 2217658 TI - Predictors of hospital outcome without antidepressants in major depression. AB - Fifty-two consecutive inpatients with nonpsychotic unipolar major depression were assessed for response to 1 week of hospitalization without antidepressants. Each was rated at admission and at 1 week using the Hamilton Rating Scale for Depression (HRSD). Fifteen of 52 responded (HRSD score less than or equal to 12), 10 of whom improved by greater than or equal to 50% change in the HRSD score. Five variables were correlated with lack of hospital response: DSM-III melancholia, panic disorder, the DSM-III-R item "absence of personality disorder," admission severity, and age. Multiple regression showed an independent association between hospital outcome and the first three variables. Response to 1 week of hospitalization was found in 70% (14 of 20) of the patients who had none of the three identified predictors: melancholia, panic, and absence of personality disorder. In patients with one or more of these predictors, only 3% (1 of 32) responded. PMID- 2217659 TI - Psychological stress and phorbol ester inhibition of radiation-induced apoptosis in human peripheral blood leukocytes. AB - Apoptosis is a process of genetically programmed alterations of cell structure that lead to failure of proliferation and differentiation, and eventual cell death. Apoptosis is induced by a variety of toxic insults including growth factor deprivation and ionizing radiation. This process may function to protect against the appearance of heritable phenotypic changes in cells and may be a critical factor in normal cellular immune function. Phorbol esters inhibit apoptosis, but little is known about factors that regulate this process physiologically. In this study, we demonstrate an association between an acute psychological stressor, taking examinations, and the induction of substantial and reversible changes in the response of peripheral blood leukocytes to gamma irradiation and to phorbol ester treatment. These data suggest that psychological stress may induce physiological changes that regulate the ability of immune cells to initiate apoptosis. PMID- 2217660 TI - Neuropsychological performance in children with Tourette's syndrome. AB - Neuropsychological performance was examined in a sample of 100 children between the ages of 6 and 18 years who met DSM-III-R criteria for Tourette's syndrome. Neuropsychological test scores were converted to age-corrected t scores based on published normative data. Ratings of Tourette's symptoms were also obtained. The mean IQ of the sample was approximately 100. Most of the subjects performed within normal limits, although approximately 20% obtained scores suggesting impairment on a summary neuropsychological performance measure. There were no differences attributable to medication effects. Later age at onset and the severity of complex tics were related to performance below normal levels on a number of neuropsychological measures. There was no specific evidence of frontal lobe dysfunction. The pattern of neuropsychological performance was virtually identical to a previously reported independent sample of patients. These data suggest a relatively characteristic pattern of neuropsychological performance abnormalities in a subgroup of patients with Tourette's syndrome. In general, most patients appear to perform within normal limits. Directions for future investigation are considered. PMID- 2217661 TI - Motor/vocal tics and compulsive behaviors on stimulant drugs: is there a common vulnerability? AB - The occurrence of abnormal movements or perserverative/compulsive behaviors was noted in 34 (76%) of a group of 45 hyperactive boys during a double-blind crossover treatment trial of methylphenidate and dextroamphetamine given in a wide range of doses. These adverse effects were often subtle and transient, and they usually occurred only on one drug. There was only one case where treatment was discontinued due to the severity of the tic the subject developed during his initial treatment phase. Dextroamphetamine tended to produce more compulsive behaviors, which were also more likely to resemble clinical obsessive-compulsive disorder (OCD), than did methylphenidate. Abnormal movements and compulsive behaviors tended to co-occur on methylphenidate only; no general "Tourette-OCD diathesis" was found for this population. PMID- 2217662 TI - Bureau of National Affairs nursing shortage review. PMID- 2217663 TI - Haemopoietic growth factors. AB - The availability of recombinant haemopoietic growth factors has permitted more precise in vitro experiments and human in vivo studies to be performed. In general, the results have been in accord with expectations from previous in vitro studies. The clinical exploitation of the haemopoietic growth factors offers great promise but careful studies are required to define their value. The effects of some growth factors are multiple and complex, and it cannot be assumed that improvements in blood cell counts are per se beneficial to the patient under all circumstances. Randomized controlled trials with clinical end-points are now essential. In the situation of chemotherapy-induced neutropenia, large studies would be required to show an improvement in mortality although lesser morbidity would be easier to demonstrate. In the field of cancer therapy the major benefit of the haemopoietic growth factors will be if they permit dosage escalation and there is a consequent improvement in response rate and long-term survival. This will require careful patient selection and large, probably multicentre, trials. It is also likely that such studies will be limited by the development of severe thrombocytopenia and an effective means to ameliorate this (perhaps the elusive thrombopoietin) will be required. The possibility of using haemopoietic growth factors as an adjunct to the treatment of severe infections is enticing, but designing a trial to evaluate this possibility is fraught with difficulties. Finally, it must be noted that all the studies reported to date use single factors. This is just the beginning and the use of other factors and synergistic combinations may give greater efficacy without increased toxicity. PMID- 2217664 TI - Clinicopathological features of childhood nephrotic syndrome in northern Nigeria. AB - The clinicopathological features of childhood nephrotic syndrome in northern Nigeria were studied in 100 consecutive patients. The patients presented with gross anasarca and very low serum albumin, which was less than 15 g/l in 30 patients. The three most frequent histological diagnoses in 98 renal biopsies were membranoproliferative glomerulonephritis (25), quartan malarial nephropathy (20), and proliferative glomerulonephritis (19): together they accounted for 65 per cent of all biopsies. Only nine patients had minimal change nephropathy. Antigens were detected by immunofluorescence in the glomeruli of 70 of 76 biopsies (92 per cent): Plasmodium malariae was detected in 25 per cent and hepatitis B surface antigen in 24 per cent. The disease was characterized by progressive deterioration in renal function and a high mortality rate of 13 per cent. Nine of the 13 deaths occurred within one year of diagnosis. PMID- 2217665 TI - Wilson's disease: 35 years' experience. AB - Thirty-seven Chinese patients fulfilling the criteria for Wilson's disease seen during a 35-year period were reviewed. Males and females were equally affected. Twenty-two patients were symptomatic and 15 asymptomatic; most of them presented before the third decade. Thirty-one per cent of the relatives screened showed evidence of disease, and parents were rarely affected (13 per cent). Half of the adult symptomatic females presented with primary amenorrhoea. Liver laboratory tests were abnormal in only 50 per cent of patients, with gamma glutamyltranspeptidase being the most sensitive index. Renal disease was infrequent. Serum caeruloplasmin level was the single biochemical parameter of prognostic significance (p = 0.0001). Seventy per cent of the symptomatic patients showed an improvement after treatment with penicillamine. PMID- 2217666 TI - The cutaneous manifestations in children with familial Mediterranean fever (recurrent hereditary polyserositis). A six-year study. AB - In a six-year study of 46 children with familial Mediterranean fever (recurrent hereditary polyserositis), 20 children (43 per cent) developed cutaneous manifestations. Ten children had 18 episodes of erysipelas-like erythema which proved to be specific for the disease. Twelve children (26 per cent) had 31 episodes of non-specific purpuric rash and six children (13 per cent) had nine episodes of Henoch-Schonlein purpura. Other manifestations included diffuse erythema of the face, and/or trunk, angioneurotic oedema, diffuse erythema of the palms and soles followed by mild desquamation of the skin, Raynaud's phenomenon and a subcutaneous nodule. The mean frequency of the cutaneous lesions was 1.6/patient/year before colchicine therapy and 0.4/patient/year after colchicine therapy (p = 0.0005). The high incidence of cutaneous manifestations and their response to colchicine strongly suggest that skin involvement is an integral part familial Mediterranean fever. PMID- 2217667 TI - Clinical, autonomic and therapeutic observations in two siblings with postural hypotension and sympathetic failure due to an inability to synthesize noradrenaline from dopamine because of a deficiency of dopamine beta hydroxylase. AB - A brother and sister with long-standing symptoms of postural hypotension are described. They were considerably worse in the morning, after exercise and in warm weather. In the male, erection was unaffected but ejaculation was prolonged or absent. Both had nocturia, but there were no urinary bladder, bowel or sweating abnormalities. Autonomic function tests confirmed sympathetic adrenergic failure with spared sympathetic cholinergic and intact parasympathetic function. There were no other neurological abnormalities. Noradrenaline and adrenaline were undetectable in the plasma, but plasma dopamine was elevated. Urinary levels of noradrenaline and adrenaline metabolites were below detection limits, but dopamine metabolites were normal or elevated. Dopamine beta-hydroxylase activity was undetectable in the plasma. Immunohistochemical studies of perivascular cutaneous tissue confirmed normal peptidergic and tyrosine hydroxylase immunoreactivity, with absent dopamine beta-hydroxylase immunoreactivity. The findings were consistent with an enzymatic deficit in the conversion of dopamine to noradrenaline. The parents were clinically and biochemically normal. Treatment of both patients with the synthetic amino acid, d-l-threo-dihydroxyphenylserine, which contains a hydroxyl group and is converted to noradrenaline by dopa decarboxylase, reduced symptoms and signs of postural hypotension and increased levels of plasma noradrenaline and its urinary metabolites. In the male, ejaculation became possible. Behavioural changes included a feeling of confidence and optimism, with a tendency to be argumentative. The laevo isomer also raised blood pressure and plasma noradrenaline levels. The drug had no direct pressor effects, as its actions were prevented by the dopa-decarboxylase inhibitor, carbidopa. PMID- 2217668 TI - Progression of diabetic autonomic neuropathy over a decade in insulin-dependent diabetics. AB - The prognosis for diabetics with autonomic neuropathy is little known. We therefore studied the progress of young insulin-dependent diabetics, first identified as having abnormal autonomic function 10-15 years ago. We have shown that the mortality of diabetics with symptomatic autonomic neuropathy is increased, but is less than previously reported. Mortality in asymptomatic diabetics with an isolated abnormality in autonomic function tests is not increased. The heart rate variability declines at 1.02 +/- 0.47 (SD) per annum in diabetics with an initially normal heart rate variability. While symptoms of autonomic neuropathy do not usually remit even over a decade, they do not commonly progress. Three groups of young insulin-dependent diabetics had heart rate variability tested between 1972 and 1977 and have been reviewed 10-15 years later. Group A (n = 49) had symptomatic autonomic neuropathy and an abnormal heart rate variability (less than 12), Group B (n = 24) were asymptomatic yet had an abnormal heart rate variability and Group C (n = 38) were asymptomatic and had a normal heart rate variability (16-26). The 10-year survival in Group A (73.4 per cent) was less (P less than 0.05) than in Groups B (91.7 per cent) or C (89.5 per cent) which did not differ from each other. The 18 Group A deaths were due predominantly to renal failure (n = 4), myocardial infarction in patients with nephropathy (n = 3) and sudden unexpected death (n = 3). The chief symptoms of autonomic neuropathy--diarrhoea, postural hypotension and gustatory sweating, were very persistent but did not necessarily deteriorate or become disabling in the majority of patients. The development of autonomic symptoms in asymptomatic patients with abnormal heart rate variability was uncommon over a decade. PMID- 2217669 TI - A study to assess the efficacy of chemoprophylaxis in the prevention of endoscopy related bacteraemia in patients aged 60 and over. AB - Five hundred and fifteen patients aged 60 and over (mean age 74.7; 278 men and 237 women) underwent routine endoscopic procedures (gastroscopy, bronchoscopy and cystoscopy). Alternate patients were given antibiotics before the procedure, as currently recommended, and blood was taken for culture from all patients within five minutes of completion of the procedure. Of 74 patients who underwent bronchoscopy, only one culture, from one of 37 controls was positive. Of 262 who underwent gastroscopy, cultures were negative in the 130 who received antibiotics but positive in 13 of the 132 controls (9.8 per cent p less than 0.001). Cystoscopy was performed in 179; one culture was positive in the 88 given antibiotics (1.1 per cent) compared to 25 in the 91 controls (27.5 per cent; p less than 0.001). Bacteraemia rates appear to be low following bronchoscopy (less than 5 per cent) but higher with gastroscopy (10 per cent) and cystoscopy (28 per cent). Chemoprophylaxis was effective in reducing these rates in this patient group. PMID- 2217670 TI - The mouth in human immunodeficiency virus (HIV) infection. PMID- 2217671 TI - Rehabilitation after stroke. PMID- 2217672 TI - Hyponatraemia in patients with cirrhosis. AB - Hyponatraemia occurs in nearly half of patients in hospital with cirrhosis and ascites, and is due to the excessive retention of free water which results from the kidney's inability to excrete it normally. The morbidity and mortality associated with hyponatraemia is largely attributable to central nervous system disturbances. The degree to which brain water content increases depends on the duration of hyponatraemia and on compensatory mechanisms. Altered steroid and peptide hormones in cirrhotic patients may contribute to the development of hyponatraemic encephalopathy, symptoms of which overlap with hepatic encephalopathy and uraemia. The occurrence of central pontine myelinolysis is unrelated to the rate of correction of hyponatraemia. The appearance of hyponatraemia in cirrhotic patients, long regarded as a poor prognostic sign, may be a function of unrecognized underlying impaired renal function. Therapy for hyponatraemia remains suboptimal. PMID- 2217673 TI - Prognostic factors in acute renal failure following aortic aneurysm surgery. AB - This study analyses the prognostic factors associated with survival in 70 patients who developed acute renal failure following surgery for an aortic aneurysm. Forty-nine patients (70 per cent) had surgery for a ruptured aortic aneurysm and 21 patients (30 per cent) had an elective procedure. Fifty-nine patients received haemodialysis. Thirty-three patients (47 per cent) survived the episode of acute renal failure. Six of these thirty-three patients died within three months of recovering from acute renal failure, giving an overall survival of 27/70 (39 per cent). A stepwise logistic regression analysis showed that the following factors significantly adversely affected survival: a need for inotropic support, ventilation for more than three days and age over 65 years. A model developed using these variables provided a basis for predicting outcome. PMID- 2217674 TI - Alpha 1-antitrypsin granules in the liver--always important? AB - We have studied the clinical histories and liver biopsy findings in 1951 consecutive adult patients with suspected chronic liver disease, and in four known PiZ-homozygous alpha 1-antitrypsin-deficient patients with emphysema (candidates for lung transplant) and no known liver disease, in order to assess the importance of periportal alpha 1-antitrypsin granules in the liver and their possible causal role in liver disease, and to assess the value of possible screening tests. Periportal granules were found in 30 (1.5 per cent) of the 1951 liver biopsies and in all four known PiZ-homozygous subjects. They were the sole putative aetiological agent in eight of 85 patients (9.4 per cent) with otherwise cryptogenic cirrhosis and present in 2.5 per cent of patients with cirrhosis of known aetiology (alcohol, autoimmune etc.). All but one were Z phenotype (seven homozygotes, 22 heterozygotes). alpha 1-Antitrypsin granules were seen in 12 patients (including three of four lung transplant candidates) with no histological chronic liver disease. Determination of serum alpha 1-antitrypsin levels was quite unhelpful in identifying these patients. This study does not support the concept that periportal alpha 1-antitrypsin granules are necessarily pathogenic, but in some cases they may be causally related to otherwise cryptogenic liver disease. The presence of granules gave no important diagnostic, therapeutic or prognostic information. PMID- 2217675 TI - Final outcome of ursodeoxycholic acid treatment in 126 patients with radiolucent gallstones. AB - One hundred and twenty-six patients with radiolucent gallstones in 'functioning' gallbladders were treated with 8-10 mg ursodeoxycholic acid (UDCA) kg/day and followed to a treatment conclusion. Complete or partial gallstone dissolution was achieved in 74 (59 per cent). However, only 22 achieved complete gallstone dissolution, as judged by two normal oral cholecystograms; ultrasonograms were performed in 16 of these patients, and all were normal. UDCA was stopped in 76 patients: because of cystic duct obstruction (n = 12), severe biliary pain (n = 13), non-response (n = 25) or partial stone dissolution with arrested progress (n = 26). Life-table analysis showed that complete gallstone dissolution rates at four years were 25-30 per cent (two normal oral cholecystograms) and 17-19 per cent (two normal oral cholecystograms plus one ultrasonogram). All patients with complete gallstone dissolution had shown partial stone dissolution at 6-12 months; of those with partial stone dissolution at six months, only 25 per cent went on to complete gallstone dissolution, and then always within two years. Efficacy correlated inversely with stone size but not with age, sex, obesity or on-treatment saturation indices. Acquired surface gallstone calcification developed in 13 patients (life-table analysis 22 +/- 7 per cent at four years); none of these patients achieved complete gallstone dissolution and only five achieved partial stone dissolution. Thus, despite relatively high partial gallstone dissolution rates, the ultimate efficacy of UDCA in achieving complete gallstone dissolution is low. PMID- 2217676 TI - Natural history and cardiac manifestations of homozygous familial hypercholesterolaemia. AB - Forty-nine patients with homozygous familial hypercholesterolaemia (diagnosed on the basis of family history, xanthomatosis, total serum cholesterol and low density lipoprotein receptor status) were studied over a period of 13 years, and underwent cardiovascular assessment. Eleven died, nine of myocardial infarction. Seven underwent coronary artery bypass, and another five had surgery to relieve supravalvular and valvular aortic stenosis. A distinctive pattern of disease was noted. Coronary ostial stenosis (four patients) and aortic root stenosis (six patients), both consequences of aortic root cholesterol deposition, were the typical manifestations of heart disease in childhood and adolescence. Adults developed severe coronary artery disease with a high incidence of main stem lesions (four of five patients). Surgery provided effective treatment for coronary artery disease and aortic outflow tract stenosis. Overall survival appeared to be better than reported in other studies which may reflect the 'receptor-defective' status of this group of patients. PMID- 2217677 TI - Oral findings in HIV-infected patients attending a department of internal medicine: the contribution of intraoral examination towards the clinical management of HIV disease. AB - The occurrence of oral mucosal lesions was studied in 70 consecutive human immunodeficiency virus (HIV)-infected patients, including 35 patients with AIDS, who had been admitted to a Department of Internal Medicine. Lesions of the oral mucosa were observed in 52 patients (74 per cent). Oral candidiasis (50 per cent), hairy leukoplakia (14 per cent), periodontal disease (13 per cent), and oral Kaposi's sarcoma (4 per cent) were the most common lesions. Oral mucosal lesions suggestive of HIV infection were present in ten of 12 patients of unknown HIV status in whom Pneumocystis carinii pneumonia was suspected. Close cooperation between the medical and dental professions is recommended since accurate intraoral examination can make a valuable contribution towards the clinical management of HIV-infected patients and may influence the CDC classification of this disease. PMID- 2217678 TI - A predominantly adrenaline-secreting phaeochromocytoma. AB - A 61-year-old woman who presented with diabetes, nausea, weight loss and sweating was found to have a phaeochromocytoma secreting adrenaline, with a small amount of N-methyladrenaline. There was no significant increase in noradrenaline secretion. She was normotensive, and developed profound hypotension in response to the alpha-adrenergic antagonist phenoxybenzamine. These features are unusual in phaeochromocytoma, but similar features occurred in the very few previous reported cases of pure adrenaline-secreting phaeochromocytoma. We conclude that it is important to identify such patients, so that they should not be given alpha adrenergic antagonist drugs. PMID- 2217679 TI - Endocarditis in the 80s in a general hospital in Auckland, New Zealand. AB - The clinical and investigative features of 102 episodes of infective endocarditis were analysed retrospectively. The most frequent presenting symptoms (malaise, fever, sweats, myalgia, weight loss) were non-specific. Fever, cardiac murmur, tachycardia, vascular phenomena and a change in mental state were the most common physical signs at admission. Anaemia was present in half the episodes and renal and liver dysfunction in about one-third. Streptococci (61) and staphylococci (31) were the causative organisms in all but 10 episodes. The commonest predisposing factors were underlying cardiac disease (52 per cent) and a preceding focus of infection (14.6 per cent). Left ventricular failure (33 per cent) and focal neurological disease (29 per cent) occurred frequently. Valvular surgery was performed in 20 episodes, with two in-hospital deaths. Overall hospital mortality was 27.5 per cent and death was most commonly neurological (11/28). A higher mortality was associated with elevated total white blood count, microscopic haematuria, renal or liver dysfunction at admission, S. aureus endocarditis, the development of left ventricular failure or focal neurological disease, age greater than or equal to 60 years and persistence of fever after one week of antibiotic therapy. The absence of both renal dysfunction at admission and subsequent microscopic haematuria identified a group with a very low hospital mortality (4.7 per cent). The three-year mortality of the entire group was 43.5 per cent. PMID- 2217680 TI - Clinical diagnosis of tamponade in Malawi. AB - A consecutive series of 25 Malawian patients with tamponade secondary to tuberculosis were compared to 25 patients with congestive cardiac failure, without pericardial effusion in a retrospective study. More patients with tamponade had an impalpable apex beat (21/1), pulsus paradoxus (13/0), soft heart sounds (13/2), paradoxical rise in jugular venous pressure (6/0), and fewer had a murmur (1/14). All these results are significant (p less than 0.05) by the chi 2 test with Yates' correction. The presence of two or more of these discriminating physical signs has a positive predictive value of 75 per cent, and a negative predictive value of 99.5 per cent for the diagnosis of tamponade. Clinical diagnosis of tamponade by primary health care personnel in Malawi should be possible, and lead to earlier treatment. PMID- 2217681 TI - Diabetic nephropathy. PMID- 2217682 TI - Properties of parathyroid hormone-related protein and its role in malignant hypercalcaemia. PMID- 2217683 TI - Diagnosis and management of pulmonary thromboembolism. PMID- 2217684 TI - Double-blind randomized study of prolonged higher-dose oral amoxycillin in purulent bronchiectasis. AB - Thirty-eight patients with bronchiectasis and daily expectoration of purulent sputum despite conventional antibiotic courses were randomly allocated to receive a sachet of amoxycillin (3 g) or matched placebo twice daily for 32 weeks in a double-blind study. Nine patients (four amoxycillin, five placebo) were withdrawn from the study treatment; the response of the two patients (both on amoxycillin) withdrawn within the first six weeks was not assessed. The pretreatment characteristics of the two groups were similar. Independent assessment of overall response based on patients' diary cards showed that a higher proportion improved in the amoxycillin group (11 of 17) than in the placebo group (four of 19; p = 0.02). Patients in the amoxycillin group spent significantly less time confined to bed and away from work during treatment. The frequency of exacerbations during the study treatment phase was similar in the two groups but they were less severe than before study treatment in the amoxycillin group. There was a greater reduction in purulent sputum volume between exacerbations during the study treatment in the amoxycillin group to 20 per cent of pretreatment volume than in the placebo group (88 per cent of pretreatment volume, p = 0.008), although the concentrations of Haemophilus spp. in sputum between exacerbations was similar in the two groups. Adverse effects experienced were minor except in one patient (amoxycillin) withdrawn after developing a rash and in six patients (three amoxycillin, three placebo) who had diarrhoea lasting more than one week necessitating withdrawal of two patients (one amoxycillin, one placebo) from study treatment. Sputum and stool cultures collected regularly during the study showed no important changes in the bacterial flora in either group. Prolonged higher-dose antibiotic therapy in these patients with severe purulent bronchiectasis significantly reduced the host (patient) inflammatory response to colonizing microorganisms and reduced morbidity. PMID- 2217685 TI - Defect in thermoregulation in malnutrition reversed by weight gain. Physiological mechanisms and clinical importance. AB - Previous studies in infants and in the elderly have shown that a low body weight is associated with a defect in thermoregulation and an increased risk of hypothermia. In the present study, thermoregulatory responses to a cooling stimulus were measured in 10 young and middle-aged patients who lost at least 10 per cent of their body weight during illness. Investigations were performed before and after restoration of body weight (mean weight gain 7.2 kg, SE 1.2 kg, p less than 0.001). The cooling stimulus was provided by a special suit perfused with water at 28 degrees C and then at 23 degrees C. Before weight gain, there was no increase in metabolic rate in response to cooling, despite a fall in core temperature. Following weight gain, the thermogenic response to cooling was restored towards normal. Peripheral vasoconstriction, the principal mechanism for heat conservation, was similar before and after weight gain. The thermogenic response to an infusion of adrenaline (25 ng/kg/min) was not abolished by weight loss, suggesting that the defect in cold-induced thermogenesis following weight loss is due to a change in central control mechanisms of thermoregulation, and not to tissue unresponsiveness. The phenomenon of abnormal thermoregulation following weight loss and the return to normal with subsequent weight gain may be clinically important, particularly in the elderly, since quite small falls in core temperature may impair both neuromuscular coordination and cerebral function. PMID- 2217686 TI - The prevalence and risk factors associated with the onset of diabetic nephropathy in juvenile-onset (insulin-dependent) diabetics diagnosed under the age of 17 years in Leicestershire 1930-1985. AB - The prevalence of diabetic nephropathy was studied in a population of 847 juvenile-onset (insulin-dependent) diabetics diagnosed under the age of 17 years who attended diabetic clinics in Leicestershire between 1930 and 1985. Seven hundred and eighty-nine patients (93.2 per cent) were traced. Eight patients with non-diabetic proteinuria and four classified as maturity-onset diabetics of the young were excluded from further analysis. The mean age at onset was 9.3 +/- 4.2 years (mean +/- SD) and the mean duration of diabetes 17.0 +/- 10.6 years (range 3-63 years). Overall, 28 patients (3.6 per cent) developed persistent proteinuria and 39 patients (five per cent) intermittent proteinuria. End-stage renal failure developed in eight patients. In patients with diabetes of 20 years duration (n = 254) the prevalence of persistent proteinuria was 9.1 per cent and of intermittent proteinuria, 7.9 per cent. Systolic and diastolic blood pressures were elevated in diabetics with persistent proteinuria compared to patients without proteinuria (154/89 +/- 27/15 vs 123/76 +/- 15/9 mm Hg mean +/- SD; p less than 0.001). Systolic blood pressure was also raised in patients with intermittent proteinuria (133/77 +/- 17/12, p less than 0.005). In addition, proteinuria (intermittent and persistent) was significantly associated with the use of once-daily insulin therapy in childhood and poor clinic attendance. This study suggests that twice-daily insulin therapy from diagnosis in childhood and regular contact with the diabetic clinic decreased the prevalence of diabetic nephropathy in this population. PMID- 2217687 TI - Subacute sclerosing panencephalitis in black children--a review of 18 cases. AB - Despite the fact that measles is severe and presents in very young Black children in Natal, South Africa, no case of subacute sclerosing panencephalitis was reported from this region prior to 1982. A retrospective study was therefore made over the six-year period 1982-1987 of 18 patients who presented to the King Edward VIII teaching hospital, Durban, with clinical and laboratory features of subacute sclerosing panencephalitis. The majority of patients (66 per cent) were between 8 and 12 years of age. The mean age of onset was 9.3 years, the youngest patient being four years nine months and the oldest 14 years. The male to female ratio was 1.25:1. A previous history of primary measles infection was obtained in 44.4 per cent of cases; 62.5 per cent occurred before the second birthday. The commonest mode of presentation was personality, intellectual and behaviour disorders (83 per cent) followed by myoclonic seizures (61 per cent) and choreiform movements (28 per cent). Measles antibody was present in the CSF in all cases. The EEG was abnormal in all recorded cases with pathognomonic periodic complexes being found in 56.2 per cent. Confirmation of the diagnosis was provided by brain biopsy in two cases and by necropsy in one case. The findings of this study suggest that subacute sclerosing panencephalitis may not be as uncommon in Black children as has hitherto been thought. PMID- 2217690 TI - [Amalgam--material and clinical aspects]. PMID- 2217688 TI - Studies on the pathogenesis of hypertension in Cushing's disease and acromegaly. AB - The pathogenesis of the hypertension associated with Cushing's syndrome and with acromegaly is poorly understood. We have investigated the possible roles of sodium retention, activation of the renin-angiotensin system and increased sympathetic nervous system activity in untreated patients. In 11 patients with Cushing's disease, seven of whom were hypertensive, total exchangeable sodium was normal despite increased levels of the mineralocorticoid hormones, 11-deoxy corticosterone and corticosterone. The renin-angiotensin system was also normal. Cardiac sensitivity to the beta-receptor agonist isoprenaline was increased, but this was not due to an increase in beta-adrenoceptor density. Hypertension in Cushing's disease is neither sodium-dependent nor angiotensin II-mediated, but increased cardiac sensitivity to catecholamines, by increasing cardiac output, may contribute to the pathogenesis of hypertension. In nine patients with acromegaly (three of whom were hypertensive) total exchangeable sodium was elevated. Although no correlation between blood pressure and exchangeable sodium was found, hypertension in acromegaly is probably sodium dependent. No evidence was found for a pathogenetic role for either the renin-angiotensin-aldosterone or the sympathetic nervous system. PMID- 2217689 TI - [Effect of force and torque on Branemark implants]. PMID- 2217691 TI - [Adhesive bridges today]. PMID- 2217692 TI - [Metal ceramic and full ceramic restorations (2)]. PMID- 2217693 TI - [Modified plate apparatus and its different applications (4)]. PMID- 2217694 TI - [Investigation of periodontal condition of orthodontic patients under various conditions in Periotest procedures]. PMID- 2217695 TI - [Interpretation of radiographs]. PMID- 2217696 TI - [ABC of practice management: E--effective decisions]. PMID- 2217697 TI - [Comparative investigations of anesthetic activity of 2- and 4% Articain]. PMID- 2217698 TI - [Modern amalgams--polishing and corrosion prevention in in vitro study. 1. Material and methods]. PMID- 2217699 TI - [Procedures with Khoury's bone cover method for mandibular molar root resection in everyday practice]. PMID- 2217700 TI - [Two-year clinical study of Luxafill filling material for fissure filling and Class I composite fillings]. PMID- 2217701 TI - [Prosthetic rehabilitation after jaw tumor resection--case report]. PMID- 2217702 TI - [Molar distalization with intraoral molar distalization bow--method for controlled position of 6-year molars in Class I relation (1)]. PMID- 2217704 TI - [Modern dental photo system with autofocus function]. PMID- 2217703 TI - [Action of different mouthwash solutions on infection rate of gingiva --study with army recruits]. PMID- 2217705 TI - [Interpretation of radiographs]. PMID- 2217706 TI - [ABC of practice management: L--leadership]. PMID- 2217707 TI - [Germ colonization from dental treatment procedures with and without disinfection processes]. PMID- 2217709 TI - [Dental assistant as office manager]. PMID- 2217708 TI - [Modern amalgams--polishing and corrosion prevention in in vitro study. 2. Results]. PMID- 2217710 TI - [Situation of dental assistant in Greece]. PMID- 2217711 TI - [Success, what is it? Four years prevention in Hamburg kindergarten (1)]. PMID- 2217712 TI - [Applied psychology in the dental office (6)]. PMID- 2217713 TI - [Material comparison. 3. Endodontic instruments and materials (2)]. PMID- 2217714 TI - [Ludwig's technic. 4. Placement of middle value articulator and positioning of Ludwig's-Technic-Cap]. PMID- 2217715 TI - [Anchor technic with system]. PMID- 2217716 TI - [Single unbiased procedure for control of precision dental casting]. PMID- 2217717 TI - [Preparation of ceramic blended bridges with Sunrise metal-ceramic system]. PMID- 2217718 TI - [From deciduous teeth to a beautiful permanent dentition--main issues of correction of deciduous teeth (2)]. PMID- 2217719 TI - [Impression aids for synthetic resin prostheses using injection procedure]. PMID- 2217720 TI - Modulation of intercellular communication during radiation and chemical carcinogenesis. AB - Carcinogenesis is a multistep process, involving the irreversible conversion of a stem cell to a terminal-differentiation-resistant cell ("initiation"), followed by the clonal expansion of this cell ("promotion") and by the acquisition of other genetic alterations leading to malignancy ("progression"). The initiation and progression steps seem to be facilitated by mutagenesis. Promotion has been associated with agents and conditions that cause mitogenesis. Gap junctional intercellular communication, a fundamental biological process regulating cell growth and differentiation, has been postulated to play a major role in carcinogenesis. The hypothesis is supported by the fact that many cancer cells have some dysfunction in gap junctional intercellular communication, many tumor promoting chemicals and several oncogenes (i.e., ras, src, mos, neu, but not myc) reduce gap junctional intercellular communication, and several growth factors (i.e., EGF, TGF-beta, bovine pituitary extract) inhibit gap junction function. This integrative concept postulates that chemical promoters, oncogenes coding for growth factors, receptors, or transmembrane signaling elements, and growth factors can isolate an initiated cell from the suppressing influence of surrounding normal cells by down-regulating the transfer of ions and small molecules through gap junctions. PMID- 2217721 TI - Role of gap junctional cell/cell communication in the control of proliferation and neoplastic transformation. AB - The C3H/10T1/2 cell system has been widely used as a quantitative assay for neoplastic transformation. Following exposure to chemical or physical carcinogens, there is a dose-dependent induction of neoplastic transformation in a small percentage of surviving cells. The ability of carcinogen-initiated cells to undergo transformation is highly dependent upon the effects of cell population density and is also inhibited by cancer chemopreventive retinoids. It is proposed that these observations are functionally related. Inhibition of transformation by retinoids correlates strongly with their ability to up-regulate intercellular gap junctional communication in normal and carcinogen-initiated cells while inhibition due to density effects correlates with the proximity of initiated cells to normal cells. It is hypothesized that junctional communication allows the transfer of signal molecules which suppress neoplastic transformation. PMID- 2217722 TI - Concepts for describing the interaction of two agents. AB - This paper reviews general concepts for understanding the effects of two or more agents. Models describing exposures to mixed fields of radiation are developed on the basis of very general postulates, and some of their consequences are examined against a set of experimental data. PMID- 2217723 TI - Effect of gamma radiation on membrane fluidity of MOLT-4 nuclei. AB - These experiments measured the effect of gamma radiation on the nuclear envelope using doxyl-fatty acid spin-label probes. Nuclei were isolated from cultured MOLT 4 cells, a radiation-sensitive human T-cell lymphocyte. Membrane fluidity was measured from the electron paramagnetic resonance spectra of the probes. MOLT-4 cells were grown under standard conditions, and suspensions were exposed to 60Co gamma radiation at room temperature. The spectra of 5-doxylstearic acid in the nuclei were those of a strongly immobilized label. A difference in the membrane fluidity was detected in a series of experiments comparing labeled irradiated and nonirradiated nuclei. The change in fluidity was measured by comparing the changes in the order parameter, S, of the spin label in irradiated nuclei with those in control nuclei. The change in the S ratio is dependent on radiation dose, increasing with doses up to 15 Gy. The maximum change of the order parameter with time after irradiation occurs 16-20 h after radiation exposure. These observations are correlated with changes in cell viabilities. PMID- 2217724 TI - Radiation-induced binding of DNA from irradiated mammalian cells to hydroxyapatite columns. AB - In experiments designed to measure radiation-induced DNA damage using the DNA unwinding-hydroxyapatite chromatography technique, we observed that under some experimental conditions a significant proportion of the test DNA became tightly bound to the hydroxyapatite (HA) and could not be released even with a high concentration of phosphate buffer. Approximately 5-10% of DNA from unirradiated cells binds to the HA. With increasing radiation doses in air, the fraction of bound DNA increases, reaching about 30% at about 35 Gy. The binding exhibits many of the characteristics of a radiation-induced cell lesion: the proportion of DNA retained by the HA is less when cells are irradiated under hypoxic conditions or in the presence of the thiol radioprotector dithiothreitol; and the binding decreases when an incubation period is allowed between irradiation and harvest of the cells for assay. Studies to determine the nature of the lesion responsible for the binding demonstrated that lesion production requires a component found in cells since no binding was observed with irradiated isolated DNA or nuclear matrix; the binding is not a result of the production of DNA-protein crosslinks; and the bound DNA is single-stranded, based on its sensitivity to nuclease S1. Because of the dose dependence of the binding of DNA to HA, the slopes of the dose-response curves for DNA damage determined with this assay depend on the method used to calculate the fraction of double-stranded DNA. Our demonstration that the bound DNA is single-stranded guides the choice of the method for data analysis. PMID- 2217725 TI - Allowing for random errors in radiation dose estimates for the atomic bomb survivor data. AB - The presence of random errors in the individual radiation dose estimates for the A-bomb survivors causes underestimation of radiation effects in dose-response analyses, and also distorts the shape of dose-response curves. Statistical methods are presented which will adjust for these biases, provided that a valid statistical model for the dose estimation errors is used. Emphasis is on clarifying some rather subtle statistical issues. For most of this development the distinction between radiation dose and exposure is not critical. The proposed methods involve downward adjustment of dose estimates, but this does not imply that the dosimetry system is faulty. Rather, this is a part of the dose-response analysis required to remove biases in the risk estimates. The primary focus of this report is on linear dose-response models, but methods for linear-quadratic models are also considered briefly. Some plausible models for the dose estimation errors are considered, which have typical errors in a range of 30-40% of the true values, and sensitivity analysis of the resulting bias corrections is provided. It is found that for these error models the resulting estimates of excess cancer risk based on linear models are about 6-17% greater than estimates that make no allowance for dose estimation errors. This increase in risk estimates is reduced to about 4-11% if, as has often been done recently, survivors with dose estimates above 4 Gy are eliminated from the analysis. PMID- 2217726 TI - Radiosensitivity increases with differentiation status of murine hemopoietic progenitor cells selected using enriched marrow subpopulations and recombinant growth factors. AB - The radiosensitivity of populations of colony-forming cells (CFC) in murine bone marrow was investigated using different recombinant colony-stimulating factors (CSFs; murine IL-3 and granulocyte-macrophage CSF and human granulocyte CSF), or purified murine macrophage CSF. With unfractionated normal bone marrow the CFC increased in radiosensitivity as they progressed through the granulocyte lineage. The D0 values ranged from 129 +/- 12 cGy for CFC stimulated with GM-CSF down to 42 +/- 2 cGy after stimulation with G-CSF. IL-3 stimulated a CFC population which gave the only survival curve with a shoulder (n = 1.9 +/- 0.3). With semipurified populations of primitive or bipotential CFC, D0 values were generally lower with respect to the equivalent values for unpurified bone marrow (range 62 +/- 7 cGy to 135 +/- 7 cGy). Changes in cluster/colony ratio and colony morphology together possibly with products of accessory cells influence the interpretation of the radiosensitivity parameters. PMID- 2217727 TI - Immunoprecipitation of pyrimidine(6-4)pyrimidone photoproducts and cyclobutane pyrimidine dimers in uv-irradiated DNA. AB - Biological studies suggest that a significant proportion of the cytotoxicity observed in mammalian cells after uv irradiation may be due to damage other than cyclobutane dimers in DNA. Although pyrimidine-pyrimidone (6-4) photoproducts have been implicated as major contributors to cell lethality, their induction has been measured at considerably less than cyclobutane pyrimidine dimers when measured by chromatographic techniques. Because the yield of (6-4) photoproducts may be reduced by their lability to extreme heat and pH, we have advised an alternative, immunological quantification which does not require DNA hydrolysis. Affinity-purified rabbit antisera were used to precipitate low molecular weight 32P-labeled PM2 DNA irradiated with increasing fluences of uv light. DNA of known molecular weight was used to determine rates of induction for antibody-binding sites associated with (6-4) photoproducts and cyclobutane dimers. These rates were calculated to be 0.6 (6-4) photoproducts and 1.2 cyclobutane dimers/10(8) Da/J/m2. At low uv fluences (6-4) photoproducts were induced at one-half the rate of cyclobutane dimers, whereas at higher fluences (6-4) photoproducts predominated. PMID- 2217728 TI - Radiobiology of alpha particles. I. Exposure system and dosimetry. AB - A 238Pu alpha-particle exposure apparatus was designed and constructed for use in radiobiological studies with cultured cell systems. The system provides a wide dynamic range of absorbed doses and a uniform radiation field. Average dose rate in air was measured with a small-volume ionization chamber. Estimates of dose rate at the cell surface were obtained from measurements taken with a silicon surface barrier detector. Particle fluence uniformity and fluence rate were measured using track etch procedures. The design and dosimetric characterization of the apparatus are discussed. PMID- 2217729 TI - Constraints to DNA unwinding near radiation-induced strand breaks in Ewing's sarcoma cells. AB - Ewing's sarcoma cell lines were compared to other cell lines for induction of DNA strand breaks by ionizing radiation and their ability to repair those breaks. The alkali-unwinding assay and alkaline sucrose gradient analysis were used for these studies. The alkali-unwinding assay revealed that the amount of DNA unwound per strand break in Ewing's sarcoma cells was less than for other cells and was not influenced by high-salt denaturation conditions. Ewing's sarcoma cells had similar induction and repair rates for strand breaks compared with other cell lines. The kinetics of unwinding suggests there are constraints to DNA unwinding in the chromatin of Ewing's sarcoma cells, possibly related to high levels of poly(ADP-ribose) polymerase in these cells. PMID- 2217730 TI - Cancer mortality following radium treatment for uterine bleeding. AB - Cancer mortality in relation to radiation dose was evaluated among 4153 women treated with intrauterine radium (226Ra) capsules for benign gynecologic bleeding disorders between 1925 and 1965. Average follow up was 26.5 years (maximum = 59.9 years). Overall, 2763 deaths were observed versus 2687 expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.03]. Deaths due to cancer, however, were increased (SMR = 1.30), especially cancers of organs close to the radiation source. For organs receiving greater than 5 Gy, excess mortality of 100 to 110% was noted for cancers of the uterus and bladder 10 or more years following irradiation, while a deficit was seen for cancer of the cervix, one of the few malignancies not previously shown to be caused by ionizing radiation. Part of the excess of uterine cancer, however, may have been due to the underlying gynecologic disorders being treated. Among cancers of organs receiving average or local doses of 1 to 4 Gy, excesses of 30 to 100% were found for leukemia and cancers of the colon and genital organs other than uterus; no excess was seen for rectal or bone cancer. Among organs typically receiving 0.1 to 0.3 Gy, a deficit was recorded for cancers of the liver, gall bladder, and bile ducts combined, death due to stomach cancer occurred at close to the expected rate, a 30% excess was noted for kidney cancer (based on eight deaths), and there was a 60% excess of pancreatic cancer among 10-year survivors, but little evidence of dose-response. Estimates of the excess relative risk per Gray were 0.006 for uterus, 0.4 for other genital organs, 0.5 for colon, 0.2 for bladder, and 1.9 for leukemia. Contrary to findings for other populations treated by pelvic irradiation, a deficit of breast cancer was not observed (SMR = 1.0). Dose to the ovaries (median, 2.3 Gy) may have been insufficient to protect against breast cancer. For organs receiving greater than 1 Gy, cancer mortality remained elevated for more than 30 years, supporting the notion that radiation damage persists for many years after exposure. PMID- 2217731 TI - Frequency of micronuclei in hepatocytes following X and fast-neutron irradiations -an analysis by a linear-quadratic model. AB - The usefulness of the micronucleus assay for investigating the radiation response of hepatocytes was examined. The frequency was defined as the ratio of the total number of micronuclei to the number of hepatocytes examined. The dose-response curves were curvilinear after X rays and linear after neutrons. These dose response curves were analyzed by a linear-quadratic model, frequency = aD + bD2 + c. The a/b ratio was 3.03 +/- 1.26 Gy following X irradiation. This value is within the range of the alpha/beta ratios reported by others using the clonogenic assay of hepatocytes. While the a/b value for neutrons was 24.3 +/- 11.7 Gy, the maximum relative biological effectiveness of neutrons was 6.30 +/- 2.53. Since the micronucleus assay is simple and rapid, it may be a good tool for evaluating the radiation response of hepatocytes in vivo. PMID- 2217732 TI - On the recommendations of ICRP/90/G-01. PMID- 2217733 TI - [Radiobiology and the lessons of Chernobyl]. AB - The Chernobyl accident has marked the beginning of a new stage of radiobiology development and revealed scantiness of old concepts. One should (1) search for effective protectors against the long-term influence of low-level radiation and means of removal of radionuclides using criteria that differ principally from those used previously in selecting among nontoxic antioxidants, immunomodulators, and adaptogens; (2) study systematically the synergism of low doses of harmful agents and review the hygienic standardization system with due regard for the risk from their combinations; (3) consider comprehensively, on the basis of the experimental and clinical experience, the problem of "hot" particles and remote consequences of their influence on the respiratory and digestive systems; (4) study independently the problem of chronic stress as a combination of radiation effects and psycho-emotional consequences of the accident and living in the exposed areas; (5) consider it inadmissible to include in the B category the population of the districts influenced by the accident and to use the concept: "35 rads during the lifetime" in standardizing the radiation load; (6) organize a comprehensive analysis of the Chernobyl accident consequences for public health within the contaminated areas as well as for animals and plants using a single approved methodology and programme, the principle of "other equal conditions" being provided. PMID- 2217734 TI - [Reciprocal translocations in mice found in the vicinity of the Chernobyl nuclear power station]. AB - A study was made of the incidence of genetic damage to germ cells of male mice taken from or exposed within the thirty-kilometer zone of Chernobyl, the contaminated no-man's-land around the reactor that failed. At all contamination levels mouse spermatocytes exhibited reciprocal translocations, a relatively low frequency of which increased with increasing dose rate. Heterozygotes, with respect to reciprocal translocations (5%), were found among males exposed to enhanced radiation background as early embryos. PMID- 2217735 TI - [Monitoring the seeds of chronically irradiated indigenous populations of Plantago lanceolata L. Variability in the progeny]. AB - The results of the morphometric study of Plantago lanceolata L. grown, in nursery, from seeds of the first and second post-accident reproductions within the thirty-kilometer zone around the crippled Chernobyl reactor show no relationship between the alterations in some quantitative indices and the variability of gamma-radiation background in places where maternal plants grow. PMID- 2217736 TI - [Partial sterility of the pine tree in 1986 and 1987 in the vicinity of the Chernobyl nuclear power station]. AB - Reproductive potency of Pinus silvestris was studied in 1986, and 1987 within the zone of Chernobyl accident by the estimates of the survival rate of seed-buds during the gametophyte and embryonal development. At the radiation level of 4 Gy a partial female pine sterility was manifested by the decreased gametophyte survival rate of seedbuds, pollinated in 1986, and by the diminished embryonal survival rate of seed-buds pollinated in 1985. PMID- 2217737 TI - [A possible molecular mechanism of the impairment of the stability of the genome in cells capable of replicating DNA in acute and chronic forms of radiation sickness]. AB - On the basis of the experimentally grounded concept concerning the functional antagonism of various domains of chromosomal SSB-proteins, that play a major role in the implementation of the contrary processes which either provide stability of DNA macromolecules or bear the responsibility for their degradation, a possible molecular mechanism of the disturbance of cell genome stability upon acute and chronic radiation sickness is discussed. PMID- 2217738 TI - [Specialized radiation-induced heritable nonstochastic damage at the cellular level of the organization]. AB - In addition to widely known stochastic mutation effects, radiation also induces qualitatively different threshold (nonstochastic) changes that influence the genome but are not conditioned by mutations. The main characteristics of these changes are: spasmodic occurrence in virtually 100% of cells; independence of radiation dose (with regard to the degree of manifestation); low inducing doses; absence of repair throughout the indefinitely large number of cell generations; nonspecificity to mutagen agents, etc. The occurrence of the above changes among objects of different organization is demonstrated and the necessity of taking them into account in estimating a radiation danger is indicated. PMID- 2217739 TI - [Morphofunctional characteristics of the liver in the cerebral form of acute radiation sickness]. PMID- 2217740 TI - [The development of neurocytes of the arcuate nucleus of the hypothalamus following whole-body gamma-irradiation of newborn rats]. AB - The results of karyometric and cytometric studies show that gamma-irradiation inhibits the growth and development of arcuate nucleus neurocytes of hypothalamus. The secretory function of neurocytes is also inhibited which is particularly important with regard to the formation of adenohypophysis functions as a major regulator of the adaptation response development. A radiation-induced disturbance of the latter aggravates the radiation injury to critical organs or systems of young animals thus influencing their viability. PMID- 2217742 TI - [The microlocalization of natural uranium in bone tissue]. AB - The author experimentally confirms the presence of a large share of uranium within the organic matrix of bone tissue and its uniform distribution within the bone mineral. It was shown in the powder-typed stratum bone cuts that the bone uranium is uniformly distributed within the bone mineral. The same is with the organic fraction of bone where uranium is uniformly distributed as well. This conclusion simplifies the calculation of the dose rate of irradiation of bone cells and red bone marrow cells with alpha-particles from the incorporated uranium, the event that these cells are plunged into a "cloud" of alpha-particles being proposed. PMID- 2217741 TI - [The interrelation of the levels of glucocorticoids and insulin in the blood of irradiated animals]. AB - Similar changes in blood levels of immunoreactive insulin (IRI) and glucocorticoids (GC) were observed in rats, mice and dogs after X-irradiation with lethal doses. The use of the blood GC/IRI ratio indices in estimating the functional status of the exposed organism is discussed. PMID- 2217743 TI - [Permissible level of laser radiation of wavelength 10.6 microns]. AB - In a four-month experiment with 102 male rabbits and 42 HRS/U mice and 30 days after termination thereof, study was made of local and general response of an organism to the effect of laser radiation (10.6 microns wave length and energy exposition 1/7 of the threshold). The radiation tolerance level was estimated. PMID- 2217744 TI - [Protein degradation during the interphase death of thymocytes induced by radiation and dexamethasone]. AB - A study was made of protein degradation in rat thymocytes after exposure to ionizing radiation and dexamethasone. The pattern of degradation of 35S methionine labelled proteins in gamma-irradiated cells and in those incubated in the presence of dexamethasone did not vary from that in control cells. No essential increase was noted in the intracellular protein degradation during interphase death of thymocytes. PMID- 2217745 TI - [Spontaneous motor activity and physical endurance of rats during acute radiation sickness developing against a background of the use of a radioprotective agent]. AB - Cystamine given to rats prior to irradiation with a dose of 8 Gy (LD77/30) ameliorates significantly the severity of radiation sickness and restores spontaneous motor activity by the time of clinical recovery. However, movements that require physical efforts as well as physical endurance remain decreased. PMID- 2217746 TI - Axillary shoulder with exaggerated rotation: the Hill-Sachs defect. AB - One of the most common fractures of the humeral head resulting from an anterior dislocation is the Hill-Sachs defect. Other special radiographic positions to demonstrate this injury may prove difficult for the patient to assume and maintain. An axillary shoulder projection with exaggerated external rotation is easy to position and clearly demonstrates the Hill-Sachs defect. PMID- 2217747 TI - A consistent method to produce lateral knee radiographs. AB - Performing lateral radiography of the knee can be challenging for the technologist because of the problem with superimposing the femoral condyles. There is an alternate method of imaging the knee in the lateral position so that the bony structures are projected to better advantage. For this method, the central ray is angled 5 degrees cephalad and the beam is aligned with the long axis of the lower leg. PMID- 2217748 TI - Interrelationship of the mind, body and emotions in the cancer fight. AB - There is an interrelationship between the mind, body and emotions in the fight against cancer. Stress seems to play a key role in the generation and continuation of cancer and there appear to be cancer-prone personality patterns associated with the propagation of increased stress levels. Psychological intervention methods have been developed to help patients cope, and the health care team can make a difference. PMID- 2217750 TI - Use of an OSCE in education for radiation therapists. AB - Concern about current clinical evaluation methods assuring attainment of basic clinical skills by radiation therapy students stimulated a project to design, develop, implement and evaluate an Objective Structured Clinical Exam (OSCE). The results suggest that the OSCE is a worthwhile, practical and effective clinical evaluation method for assessing basic clinical skills of radiation therapy students. PMID- 2217749 TI - Post-myelogram CT and the incidence of headache. AB - CT following myelography is superior to myelography alone in the diagnosis of spine disease. When using water soluble contrast, post myelogram orders include keeping the patient's head elevated. Examination by computed tomography necessitates the patient's head be lowered. This study demonstrates that post myelographic CT does not produce a significant increase in headache. PMID- 2217751 TI - Big job requires staff. PMID- 2217752 TI - Questions about questioning? PMID- 2217753 TI - [Conventional diagnosis of carpal luxation and instability]. AB - The recognition of ligament disruption in carpal dislocation and the early diagnosis of carpal instability have had implications for the therapy since the evolution of differentiated surgical treatment concepts including ligament reconstruction. Plain radiography and the carpal instability series are helpful in the detection of ligament disruption. The radiological analysis is based on the configuration and arrangement of the carpals, the setting of their axes, and the detection of intercarpal gaps. Mechanisms and characteristic radiological findings in the different types of carpal dislocation and instability (scapholunate dissociation, palmar or dorsal intercalated segment instability) are demonstrated in relation to physiological appearance, and the value of conventional films in the diagnosis of carpal dislocation and instability is discussed. PMID- 2217754 TI - [Computed tomography of the wrist]. AB - CT is a diagnostic tool that allows imaging of the wrist, wrist joint and distal radioulnar joint in the axial plane without superimposition. The differentiation of bone, joint space and soft tissue is possible in a single examination. This is helpful in the diagnosis of traumatic, degenerative or malignant lesions of bones together with the soft tissue reactions. Further information can be obtained by means of three-dimensional reconstructions. PMID- 2217755 TI - [The examination technique and normal morphology of the ligaments in MRT of the wrist]. AB - The normal ligamentous anatomy and an efficient examination technique for the wrist are demonstrated with reference to examinations conducted in healthy volunteers. Only the ulnar complex, the radial collateral ligament, the distal intercarpal ligaments and the radial parts of the palmar and dorsal V-ligaments are adequately visualized. Thus, limited specificity means that static high resolution MRI of the wrist cannot at present be considered an adequate examination method for the evaluation of unexplained wrist pain and instability. So far MRI can only play a key role in the diagnosis of lesions of the ulnar complex. PMID- 2217756 TI - [A comparison of arthrography and magnetic resonance tomography in painful limited movements of the hand]. AB - In 18 patients with unclear pain in the wrist limiting hand movement, arthrography and magnetic resonance imaging (MRI) were compared. The FISP gradient echo sequence turned out to be superior to the T1 weighted spin-echo sequence in the imaging of the triangular fibrocartilage complex. MRI is very sensitive in detecting triangular fibrocartilage lesions and therefore represents a suitable non-invasive screening method. It is, however, not possible to assess the degree of the lesion. Ruptures in carpal tendons could only be diagnosed by means of arthrography. PMID- 2217757 TI - [X-ray and ultrasonic diagnosis of rheumatic-inflammatory diseases of the elbow]. AB - The X-ray anatomy and ultrasound appearance of the normal elbow joint are described. The ultrasound testing procedure for visualizing the soft tissue layer and the intra-articular inflammatory substrate is presented. The general X-ray signs of arthritis in the elbow joint are presented, and then the radiological particularities and characteristics of the various forms of arthritis are discussed with reference to their different etiologies. PMID- 2217758 TI - [Spinal infarct? Cervical spinal stenosis? Cervical epidural hematoma]. PMID- 2217759 TI - The role of US in breast imaging. PMID- 2217760 TI - Cervical disk disease. PMID- 2217761 TI - Cloacal malformations and exstrophy syndromes. PMID- 2217762 TI - Diffusion/perfusion MR imaging of the brain: from structure to function. PMID- 2217763 TI - Sonographic determination of tubal rupture in patients with ectopic pregnancy: is it feasible? PMID- 2217764 TI - Intervertebral disk: normal age-related changes in MR signal intensity. PMID- 2217765 TI - Mammography in the eighties. AB - Mammography has experienced the greatest change of any existing radiologic examination in recent years. In 1985, as a part of the Nationwide Evaluation of X Ray Trends (NEXT) program, a national survey was conducted of a statistically selected sample (n = 232) of facilities performing mammography examinations in the United States. By 1988, the number of mammography facilities in the United States had increased to over 6,400, an increase of over 60% from the 1985 level. To assess the consequence of this expansion as well as the impact of recent technological and other significant developments on mammography, a NEXT survey of mammography facilities was repeated in 1988 (n = 226). Screen-film mammography accounted for 83% of the facilities surveyed in 1988, and dedicated equipment dominated screen-film systems (99%). There was a 26% increase in the overall mean phantom image score, over 45% increase in the use of grids, and 10% increase in mean glandular dose for systems using grids. PMID- 2217766 TI - Average radiation exposure values for three diagnostic radiographic examinations. AB - National surveys of more than 600 facilities that performed chest, lumbosacral spine, and abdominal examinations were conducted as a part of the Nationwide Evaluation of X-Ray Trends program. Radiation exposures were measured with use of a set of standard phantoms developed by the Center for Devices and Radiological Health of the Food and Drug Administration, U.S. Public Health Service. X-ray equipment parameters, film processing data, and data regarding techniques used were collected. There were no differences in overall posteroanterior chest exposures between hospitals and private practices. Seventy-six percent of hospitals used grids, compared with 33% of private practices. In general, hospitals favored a high tube voltage technique, and private facilities favored a low tube voltage technique. Forty-one percent of private practices and 17% of hospitals underprocessed their film. Underprocessing in hospitals increased from 17% in 1984 to 33% in 1987. Average exposure values for these examinations may be useful as guidelines in meeting some of the new requirements of the Joint Commission on Accreditation of Healthcare Organizations. PMID- 2217767 TI - Pulmonary neoplastic and lymphoproliferative disease in AIDS: a review. AB - Kaposi sarcoma and lymphoma are the most common forms of neoplastic disease encountered in patients with acquired immunodeficiency syndrome (AIDS). Pulmonary involvement is fairly common with Kaposi sarcoma, while lymphoma only rarely involves the lungs. There has been a significant increase in the number of AIDS patients who develop Kaposi sarcoma, especially male homosexuals. There has also been an increase in the incidence of high-grade (aggressive) lymphoma in male homosexuals (and young men in general). Lymphoid interstitial pneumonia is a chronic condition that primarily affects adults and is becoming more common in patients with AIDS. When present in children less than 13 years old, lymphoid interstitial pneumonia is considered to be an indication of AIDS. Bronchus associated lymphoid tissue and a condition resembling angioimmunoblastic lymphadenopathy are also being found in children with AIDS. A review of the literature on neoplastic and lymphoproliferative disease in AIDS suggests that a variety of lymphoproliferative disorders in AIDS can be expected in the future. PMID- 2217768 TI - Pinch-off syndrome: a complication of implantable subclavian venous access devices. AB - Implantable central venous access devices placed via the subclavian vein may become obstructed by thrombosis, impingement against a vein wall, or compression between the clavicle and first rib. The latter has been termed pinch-off syndrome (POS). Eleven patients with POS were studied, including one whose catheter had fractured and one whose catheter had fragmented. They were compared with 22 matched control patients and 100 consecutive routine clinic patients. Each catheter was graded: 0 = normal, 1 = abrupt change in course with no luminal narrowing, 2 = luminal narrowing, and 3 = complete catheter fracture. POS was present in most (eight of 11) cases within 3 weeks after placement. A grade 1 catheter was common (33%) among control subjects, but grades 2 and 3 were uncommon (1%). Catheter fracture or fragmentation was seen in two of five cases with long-term (greater than 3 weeks) pinching (grade 2 catheter). The following conclusions were reached: Grade 2 represents significant catheter compression and the potential for serious complications. Grade 1 is of uncertain clinical significance, due to its high prevalence in control subjects. PMID- 2217769 TI - Hemoptysis: CT-bronchoscopic correlations in 58 cases. AB - Computed tomographic (CT) and chest radiographic findings were retrospectively correlated with those found at fiberoptic bronchoscopy (FOB) in 58 patients presenting with hemoptysis. Abnormalities involving the airways were depicted by CT in a total of 28 cases (48%). In 18 of these (31% of the total group of 58), focal abnormalities involving the central airways were identified (17 were subsequently proved to be malignant) and in 10 (17% of the total), CT showed bronchiectasis. Focal airway abnormality was shown by FOB in 18 cases (31%); all of these were depicted with CT. Malignancy was diagnosed in 24 patients, including three in whom results of FOB were normal but malignant cells were identified at transbronchial biopsy. CT abnormalities were identified in all cases of malignancy. In 10 of 21 cases (48%) of non-small cell lung cancer, CT allowed definitive staging by documenting either direct mediastinal invasion and/or metastatic disease, while FOB allowed definitive staging in only three cases. CT studies provided no false-negative results. It is concluded that when carefully performed, CT may be an effective modality for evaluating patients presenting with hemoptysis. PMID- 2217770 TI - Coal worker's pneumoconiosis: CT assessment in exposed workers and correlation with radiographic findings. AB - To study the signs of coal worker's pneumoconiosis (CWP) at computed tomography (CT), the authors obtained thoracic CT scans in 170 coal-dust-exposed workers who were concomitantly evaluated with conventional posteroanterior and lateral radiography. The profusion and extent of disease was assessed by means of CT in two groups of miners: group 1 (n = 86), miners with worker's compensation and radiographic evidence of CWP, and group 2(n = 84), miners who had applied for compensation without radiographic evidence of CWP. The CT signs of CWP consisted of micronodules, nodules, and progressive massive fibrosis. The comparative analysis demonstrates the superiority of an optimal CT technique over chest radiography in the evaluation of simple silicosis, with improved sensitivity in the detection of small parenchymal opacities. CT provides additional information on the stage of the disease but also clarifies some ambiguities of the ILO classification of small opacities. CT was equivalent to radiography for complicated silicosis, except in the identification of necrosis. CT evaluations are complementary to plain radiography in the assessment of CWP, and the addition of high-resolution CT is useful in achieving a more accurate evaluation of the small parenchymal opacities. PMID- 2217771 TI - Persistent and recurrent hyperparathyroidism: assessment with gadopentetate dimeglumine-enhanced MR imaging. AB - The effect of gadopentetate dimeglumine on signal intensity of abnormal parathyroid glands was assessed in 14 patients with persistent and recurrent hyperparathyroidism. Non-contrast material-enhanced T1- and T2-weighted spin-echo images were compared with T1-weighted images obtained 1 minute and 10 minutes after administration of gadopentetate dimeglumine. Percentage of contrast between the abnormal gland and surrounding tissue was determined with the use of skeletal muscle, subcutaneous fat, and thyroid gland as reference tissues. All 11 abnormal parathyroid glands showed low to intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Gadopentetate dimeglumine significantly increased the signal intensity enhancement ratio of all abnormal parathyroid glands, causing increased percentage of contrast relative to the thyroid gland and skeletal muscle on T1-weighted images. However, the percentage of contrast relative to these tissues was even greater on nonenhanced T2-weighted images. Thus, gadopentetate dimeglumine can substantially enhance the signal intensity of abnormal parathyroid glands and improve differential contrast with some neighboring tissues on T1-weighted images, but it does not improve contrast with surrounding tissue beyond that achieved on T2-weighted images. PMID- 2217772 TI - Cervical lymph node metastasis: assessment of radiologic criteria. AB - To estimate the accuracy of different radiologic criteria used to detect cervical lymph node metastasis in patients with head and neck carcinoma, seven different characteristics of 2,719 lymph nodes in 71 neck dissection specimens from 55 patients were assessed. Three lymph node diameters, their location, their number, the presence of a tumor, and the amount of necrosis and fatty metaplasia were recorded. The minimal diameter in the axial plane was found to be the most accurate size criterion for predicting lymph node metastasis. A minimal axial diameter of 10 mm was determined to be the most effective size criterion. The size criterion for lymph nodes in the subdigastric region was 1 mm larger (11 mm). Groups of three or more borderline nodes were proved to increase the sensitivity but did not significantly decrease the specificity. Radiologically detectable necrosis (3 mm or larger) was found only in tumorous nodes and was present in 74% of the positive neck dissection specimens. Shape was not a valuable criterion for the radiologic assessment of the cervical lymph node status. PMID- 2217774 TI - Normal pituitary gland: coronal MR imaging of infundibular tilt. AB - To determine the prevalence of pituitary infundibular deviation or tilt as a normal variant, coronal magnetic resonance (MR) images of 50 patients who had been examined for reasons other than pituitary disease were evaluated retrospectively. Forty-six percent of the patients had a more or less pronounced tilt of the pituitary stalk. This tilt was due to developmental lateral eccentricity of the pituitary gland in relationship to the midline of the brain in 34% and to ontogenic eccentric insertion of the pituitary infundibulum off the midline of the gland in the other 12%. This high frequency of stalk deviation in patients without pituitary disease suggests that such displacement by itself should not be used to support the presence of pituitary microadenoma on MR images or computed tomograms. PMID- 2217773 TI - Intervertebral disk: normal age-related changes in MR signal intensity. AB - The effect of age on the signal intensity of normal lumbar intervertebral disks was studied. Twenty-seven cadavers ranging in age from newborn to 79 years were studied with use of a 1.5-T magnetic resonance (MR) imager within 48 hours of death. The signal intensity in the central area of the disk was measured on a sagittal image obtained with a long repetition time (TR) and a long echo time (TE) and correlated to the age. A significant correlation between the decrease in signal intensity and age was found, although signal intensity changed less than 6% in 80 years. The decrease in signal intensity is concomitant with decreases in water and glycosaminoglycans and increases in collagen in the disk. PMID- 2217775 TI - Gd-HP-DO3A in clinical MR imaging of the brain. AB - As part of a phase II clinical trial, 14 patients with presumed intracranial neoplastic disease underwent magnetic resonance (MR) imaging before and after intravenous injection of gadolinium 1,4,7-tris(carboxymethyl)-10-(2' hydroxypropyl)-1,4,7,10-tetraazacycl ododecane (HP-DO3A). This neutral (nonionic) gadolinium chelate has lower osmolality, when formulated at equimolar concentrations, and superior in vitro stability compared with gadopentetate dimeglumine. The safety profile of Gd-HP-DO3A permitted administration of doses up to 0.3 mmol/kg, three times the dose of gadopentetate dimeglumine approved by the U.S. Food and Drug Administration. In this limited clinical trial, Gd-HP-DO3A proved to be a safe and efficacious agent in MR imaging of the head. The only change documented in patient monitoring was that of slight skin redness at the injection site immediately after administration in two patients. No statistically significant changes due to administration of the agent were noted in laboratory evaluations. These results differ from those obtained with gadopentetate, which induces a transient rise in serum iron and bilirubin levels in up to 26% of patients. Administration of higher doses of Gd-HP-DO3A, either 0.2 or 0.3 mmol/kg, appeared to provide improved enhancement. No decrease in efficacy at these high doses was noted. PMID- 2217776 TI - Anisotropic diffusion in human white matter: demonstration with MR techniques in vivo. AB - Quantitative measurements of perfusion and molecular diffusion were made in human white matter in two orientations of the motion-sensitization gradient to document anisotropy of these parameters. Measurements were localized to a 10 X 10-mm tissue column oriented in an anterior-to-posterior direction in the left cerebral hemisphere just above the body of the left ventricle. This region was selected because of the relatively high directionality of white matter fibers. In this study of five healthy volunteers, strong diffusion anisotropy was observed in all cases. Twofold or greater anisotropy was commonly observed, with the higher diffusion value associated with motion sensitivity along the fiber directions. By combining data from both gradient orientations in all cases, diffusion values of solid tissue ranged from 0.38 X 10(-3) mm2/sec to 1.12 X 10(-3) mm2/sec, and measured perfusion fractions were in the range of 2%-5% (excluding areas highly contaminated by cerebrospinal fluid). Little or no perfusion-fraction anisotropy was observed; however, perfusion measurements were limited by noise. Data were collected without cardiac gating by using a technique that offers good immunity to bulk tissue motion artifacts. PMID- 2217777 TI - Echo-planar imaging of intravoxel incoherent motion. AB - The recently established single-shot technique of echo-planar imaging of intravoxel incoherent motion (IVIM) for determining and imaging the variations of microscopic motions of water has been applied to studies of water perfusion in phantoms and to in vivo studies of diffusion and perfusion in cat and human brains. The phantom results demonstrate that perfusion levels comparable with those found in vivo have easily observable and reproducible effects on signal amplitude that are consistent with previous IVIM theory. Reliable measurements of the diffusion coefficient in various types of brain tissue have been obtained. The results for white matter are consistent with the existence of anisotropic diffusion in oriented bundles of myelinated nerve fibers. The results for gray matter can be fitted to the IVIM theory and suggest a value of up to 14% for the fraction of the signal contributed by randomly perfusing fluid in normal cerebral cortex. PMID- 2217778 TI - Lumbar facet joint capsule: appearance at MR imaging and CT. AB - The joint spaces and synovium of the lumbar facet joints extend beyond the articular surfaces of the joint in the majority of adults. The authors correlated magnetic resonance (MR) imaging, computed tomographic (CT), and axial cryomicrotome sections of 66 facet joints in nine cadavers. Extensions of the synovium and joint space along the superior and inferior articular processes, under the ligamentum flavum, and into the ligamentum flavum could be recognized with use of MR and, less successfully, CT. The injection of a paramagnetic contrast medium into the facet joint facilitated visualization of the capsule on MR images. On the ventral aspect of the lumbar facet joint, MR images showed regions of high signal intensity where the joint space extended into the ligamentum flavum or between the ligamentum flavum and lamina. On the dorsal aspect of the joint, MR demonstrated prominence of the fibrous joint capsule where the joint space extended under it along the inferior articular process or along the superior articular process. The variable appearance of the ventral and dorsal aspects of the lumbar facet joint on CT and MR images is due to extension of the synovium and joint space. PMID- 2217779 TI - Temporal bone: three-dimensional CT. Part I. Normal anatomy, techniques, and limitations. AB - Three-dimensional (3D) surface renderings of the temporal bone were created from routine axial computed tomographic (CT) images in 15 subjects and in cadaver specimens. The displayed anatomy was correlated with these specimens, as well as with images from the routine study. Six sets of viewing angles were derived for optimal display of surgically important surface landmarks, such as the suprameatal triangle and supramastoid crest. The 3D CT images were found to be of excellent quality and permitted a global view of the temporal bone surface anatomy. Bone depletion artifacts ("pseudoforamina") posed a potentially serious problem in evaluating the tegmen and wall of the sigmoid sulcus, being present in eight of 20 cases. Three-dimensional CT may be a useful adjunct to routine temporal bone imaging. PMID- 2217780 TI - Development of the human cerebellum observed with high-field-strength MR imaging. AB - A retrospective study of 160 pediatric subjects, aged 32-410 weeks after conception, was conducted to determine the normal developmental patterns of the human cerebellum by means of magnetic resonance (MR) imaging. On the basis of axial T2-weighted spin-echo images (repetition time, 3,000 msec; echo time, 120 msec), which provided the best contrast between gray matter and white matter, five distinct developmental stages were defined. At term, the medial lemnisci as well as the parasagittal cerebellum were myelinated. The appearance of myelin in the middle cerebellar peduncles and the basilar pons preceded that in the corpus medullare of the cerebellum. The normal age ranges for the different stages were defined with statistical analysis. These ranges are applicable to the daily routine of image interpretation. The sequence of myelination in the cerebellum observed at MR imaging correlates with the known patterns observed in pathologic studies but lags behind by an average of 6 months. PMID- 2217781 TI - Phenylketonuria: MR imaging of the brain with clinical correlation. AB - Fifteen patients with biochemically documented phenylketonuria (PKU) were studied with use of magnetic resonance (MR) imaging with spin-echo T2-weighted pulse sequences. The resulting images demonstrated varying degrees of symmetric high signal intensity of the white matter within the posterior cerebral hemispheres. Involvement of the anterior hemispheres was seen only in cases with severe signal intensity changes. There was no involvement of the cerebral cortex, brain stem, or cerebellum. Moreover, no anatomic structural abnormalities were observed. Mild cortical atrophy was observed in eight of the 15 patients. There was no significant correlation between the patients' IQ scores and the level of MR signal intensity changes. Although MR imaging routinely shows relatively distinct abnormalities in patients with PKU, the clinical severity of the disease does not parallel its imaging severity. PMID- 2217782 TI - The cloacal malformation: radiologic findings and imaging recommendations. AB - The imaging studies and records of 65 patients with the cloacal malformation seen from 1969 to 1989 were reviewed. The malformations were described according to cloacal configuration (urethral, vaginal), type of urinary-cloacal communication (urethral, vesical), and level of rectal communication (vaginal, cloacal, vesical, other). Lower urinary tract abnormalities were frequent (reflux, ureteral ectopia, bladder diverticula, bladder duplication, urachal remnants, urethral duplication), as were genital abnormalities (uterine duplication, vaginal duplication, uterine atresia, vaginal atresia), abnormalities of the bony pelvis (partial sacral agenesis, pubic diastasis), and renal abnormalities (agenesis, obstruction, horseshoe kidney). Contrast material studies of the cloaca and the distal limb of the colostomy with fluoroscopy in various projections were essential for diagnosis. Voiding cystourethrography was important for detecting vesicoureteric reflux. Sonography was of limited value for evaluation of the malformation but was valuable for imaging the kidneys. MR imaging revealed that spinal cord abnormalities cannot be predicted based on the appearance of the lumbosacral spine and are more common than previously thought. PMID- 2217784 TI - Ligaments of the lateral aspect of the ankle and sinus tarsi: an MR imaging study. AB - The normal anatomy of the lateral ankle and subtalar ligaments seen at magnetic resonance (MR) imaging was studied in four cadaver ankles. Sixteen ankles of 11 healthy volunteers were imaged with four different MR imaging protocols to optimize technique. The anterior talofibular ligament was identified in 100% of the ankles of the volunteers in the axial plane, the calcaneofibular ligament in 81% of the ankles in the coronal plane, the cervical ligament in 69% of the ankles in the coronal plane and in 88% of the ankles in the sagittal plane, and the talocalcaneal ligament in 56% of the ankles in the coronal plane and in 62% of the ankles in the sagittal plane. It is concluded that thin-section (1-3-mm) MR imaging techniques, especially the one in which data are acquired with three dimensional Fourier transform, are best for visualization of the ligaments. These techniques may play a role in the evaluation of patients with chronic ankle pain and instability. PMID- 2217783 TI - Primary Ewing sarcoma: follow-up with Ga-67 scintigraphy. AB - While avid accumulation of gallium-67 citrate and technetium-99m methylene diphosphonate (MDP) occurs initially in most cases of primary Ewing sarcoma, uptake after therapy is less well defined. Thirty patients with Ewing sarcoma who underwent Ga-67 and bone scintigraphy at diagnosis, at completion of therapy, and at relapse from 1978 to 1988 were evaluated. All 30 patients showed less primary site Ga-67 activity following therapy. Twenty-three of 28 patients who underwent corresponding bone scintigraphy showed less uptake, but residual activity was usually more intense than with Ga-67. Avid reaccumulation of Ga-67 occurred in four of five patients with primary site relapse, while patients who underwent bone scintigraphy showed less change. It was concluded that a greater decrease in Ga-67 than in Tc-99m MDP uptake often occurs in patients successfully treated for primary Ewing sarcoma. Information obtained at Ga-67 scintigraphy is most likely to be helpful if results of bone scintigraphy remain abnormal or if occult relapse is suspected. PMID- 2217786 TI - Meniscal abnormalities in the asymptomatic population at MR imaging. AB - Two hundred eighty meniscal horns in 64 asymptomatic volunteers in the 2nd to 8th decades of life were analyzed for meniscal abnormalities. Grade 1, 2, and 3 changes were present in essentially all decades. There was at least a 25% prevalence of meniscal signal abnormalities as early as the 2nd decade. The prevalence of meniscal abnormalities increased sharply with age. The prevalence of all signal abnormalities correlated with age, grade 2 changes having the highest correlation coefficient (+.88). The correlation coefficient for grades 1 and 3 changes were +.60 and +.71, respectively. The posterior horn of the medial meniscus had a significantly higher (P less than .02) prevalence of abnormalities than did the other meniscal locations. There was no significant correlation between subject weight or sex and meniscal signal. The authors conclude that there is a baseline prevalence of meniscal signal in the asymptomatic population. PMID- 2217785 TI - Scapholunate advanced collapse: a common wrist abnormality in calcium pyrophosphate dihydrate crystal deposition disease. AB - Scapholunate advanced collapse (SLAC) is a pattern of wrist malalignment that has been attributed to posttraumatic or spontaneous osteoarthritis of the wrist. Its features, however, also have been observed in patients with idiopathic calcium pyrophosphate dihydrate (CPPD) crystal deposition disease. To determine the frequency and characteristics of SLAC in this disease, the authors reviewed wrist radiographs in 168 well-documented cases of this disorder. Forty-four of the cases (26%) revealed wrist abnormalities typical of SLAC. Associated findings included bilateral involvement (63%); calcification in or near the triangular fibrocartilage (70%); scapholunate widening or dissociation (70%); and arthropathies of the trapezioscaphoid (57%), metacarpophalangeal (second through fifth) (52%), first carpometacarpal (40%), and radiolunate (14%) joints. Results strongly suggest that CPPD crystal deposition disease is one of the major causes of SLAC. Furthermore, radiolunate arthropathy was found in 14% of the patients with SLAC and CPPD crystal deposition disease, which is different from other observations. PMID- 2217787 TI - Vertebral hemangiomas: fat content as a sign of aggressiveness. AB - Thirty-two vertebral hemangiomas (VHs) were evaluated with nonenhanced computed tomography (CT), T1-weighted magnetic resonance (MR) imaging, CT enhanced with contrast material, and selective spinal arteriography. The stroma between the osseous trabeculae was found to correspond to either fatty tissue or soft tissue or both. All 11 asymptomatic VHs showed complete fatty stroma at CT and increased signal intensity at MR imaging. In contrast, all four compressive VHs had soft tissue attenuation at CT. Three compressive VHs showed low signal intensity on MR images. Predominantly fatty stroma at CT and increased signal intensity at MR imaging were associated with normal or only slightly increased vascularization at selective spinal arteriography or contrast-enhanced CT, while soft-tissue stroma at CT and low signal intensity at MR imaging were associated with distinct hypervascularization. The authors' experience suggests that fatty VHs may represent inactive forms of VH, while soft-tissue content at CT and low signal intensity at MR imaging may indicate a more active vascular lesion with potential to compress the spinal cord. CT and MR imaging may be especially valuable for evaluating patients with clinical signs or symptoms of uncertain origin and findings compatible with VH at plain radiography. PMID- 2217788 TI - Dermatomyositis: correlative MR imaging and P-31 MR spectroscopy for quantitative characterization of inflammatory disease. AB - Magnetic resonance (MR) imaging and phosphorus-31 MR spectroscopy were used to examine four patients with dermatomyositis and five control subjects. T2-weighted images of the thigh muscles of patients showed increased signal intensity, with focal and inhomogeneous involvement predominantly in the vastus lateralis and secondarily in the vastus intermedius and vastus medialis. T1 and T2 values of the vastus lateralis in patients were significantly higher than those of the control subjects. T1 values of the rectus femoris and biceps femoris with more generalized inflammation were moderately elevated but still significantly higher than those of the control subjects. P-31 MR spectra of the quadriceps muscles were obtained during rest, during exercise at two graded levels, and in recovery. Concentrations of adenosine triphosphate and phosphocreatine (PCr) in the diseased muscles were 30% below normal values, and the inorganic phosphate/PCr ratios were increased in the patients' muscles at rest and throughout exercise. The T1 and T2 values as well as the P-31 metabolite data correlated with symptoms and clinical assessment. PMID- 2217789 TI - Can the status of tubal pregnancy be predicted with transvaginal sonography? A prospective comparison of sonographic, surgical, and serum hCG findings. AB - Results of transvaginal sonography were compared prospectively with surgical findings and levels of serum human chorionic gonadotropin in 120 women with a proved tubal pregnancy. The most common sonographic finding was a saclike adnexal ring, which was seen in 74 of the women (61.7%). This finding was strongly associated with functioning trophoblasts and with an intact fallopian tube. In 39 of the women (32.5%) an adnexal mass with a complex texture was found. Of these 39 women, 20 had a tubal hematoma and six had a ruptured fallopian tube. The size of the tubal mass created by ectopic pregnancy was predicted precisely (r = .91, P less than .001), and transvaginal sonography enabled detection of hemoperitoneum with a sensitivity of 91% (68 of 75 women). This study suggests that the status of a tubal pregnancy can be predicted reliably on the basis of transvaginal sonographic findings. PMID- 2217790 TI - Hypointense renal cell carcinoma: MR imaging with pathologic correlation. AB - In two pathologically documented cases of renal cell carcinoma, the appearance of the tumors at magnetic resonance (MR) imaging was markedly hypointense relative to normal renal parenchyma on both T1- and T2-weighted spin-echo images. Pathologic examination of both tumors revealed diffuse iron scattered throughout the tumors. The paramagnetic effect of the iron may account for this unusual hypointense appearance at spin-echo imaging, independent of pulse sequence. PMID- 2217791 TI - Intrauterine growth retardation: diagnosis based on multiple parameters--a prospective study. AB - A scoring system has previously been developed to diagnose intrauterine growth retardation (IUGR) based on three parameters: estimated fetal weight, amniotic fluid volume, and maternal blood pressure status. To test the IUGR score prospectively, the authors computed the score in 356 third-trimester fetuses, 39 growth retarded and 317 normal, scanned within 2 weeks prior to delivery. The IUGR score identified three groups, each with a distinct probability of IUGR: A score below 50 virtually excludes IUGR (3% probability), a score above 60 allows confident diagnosis (74% probability), and score of 50-60 is indeterminate (13% probability). The IUGR score performed best in patients with accurate dating by early ultrasound (US), but even among patients lacking accurate dating, the performance of the IUGR score was superior to that previously reported for any single sonographic parameter. The IUGR score can be used in any US facility to diagnose or exclude third-trimester IUGR. PMID- 2217792 TI - Lower extremity venography with iohexol: results and complications. AB - The frequency of side effects of a nonionic contrast agent (iohexol) was studied in 463 consecutive patients who underwent venography for clinically suspected deep-vein thrombosis (DVT) and compared with the frequency of adverse reactions of another series in which patients received either the same contrast material or a high-osmolar ionic compound. Minor side effects, including local pain and discomfort, nausea and vomiting, dizziness, skin reactions, superficial phlebitis, and edema, occurred in 83 patients (17.9%; 95% confidence interval [CI], 15%-22%). The only serious adverse reaction (bronchospasm) was seen in two patients (0.4%; 95% CI, 0.1%-1.4%). Postvenographic thrombosis confirmed by means of repeat venography occurred in one of 41 consecutive patients with a previous normal venogram (incidence, 2%; 95% CI, 0%-13%). The frequency of side effects appears to be significantly less than when conventional high-osmolar contrast agents are used. Use of iohexol for venography is associated with minor side effects in approximately one-fifth of patients, and serious adverse reactions necessitating therapy are rare. PMID- 2217793 TI - Biliary lithotripsy: in vitro analysis of gallstone fragmentation for equivalent stone volumes. AB - The relationship between gallstone fragmentation during extracorporeal shock wave lithotripsy (ESWL) and gallstone volume is poorly understood. Clinical results of ESWL show that the highest stone-free rate at 6 months occurs with radiolucent single gallstones 20 mm or less in diameter. In an in vitro study, individual gallstones from cholecystectomy specimens were divided by size and composition into nine single- and nine multiple-stone groups; the stones were then paired on the basis of similar volume. ESWL was performed in a phantom and the size of the largest fragment was measured at 500, 1,000, and 1,500 shock waves. At 1,500 shock waves, sandlike particles were present in six of nine single stones versus two of nine multiple stone groups; the mean size of the largest fragment at 1,500 shock waves was 2.1 mm (single) and 4.4 mm (multiple) in diameter. When corrected for volume, the authors' data suggest that single stones are more easily broken into fragments smaller than 5 mm in diameter than multiple gallstones. The implication, especially when spark-gap technology is used, is that more shock wave energy (ie, an increased number of shock waves at a higher kilovoltage) will be necessary to achieve the same results when treating patients with multiple stones versus a single gallstone with a similar stone volume. PMID- 2217794 TI - Rectal carcinoma: CT staging with water as contrast medium. AB - Computed tomography (CT) was used to study 42 patients with rectal carcinoma. Water was used as a contrast medium for studying the local extent of tumor in all patients. Scans were read prospectively without knowledge of the histologic staging and then compared with pathologic specimens. CT depicted the tumor in all patients. Comparison of CT and histologic results (following the Dukes classification) showed that disease was correctly staged as A in three of four patients, as B in eight of 12, as C in 15 of 17, and as D in nine of nine. Overall, carcinoma was correctly staged with CT in 35 of 42 patients (diagnostic accuracy, 83.3%). The accuracy in the assessment of local invasion was 97.6% (41 of 42). In the detection of lymph node involvement, the accuracy was 78.6% (sensitivity, 88%; specificity, 64.7%). CT is recommended in the preoperative staging of rectal carcinoma and as an aid in choosing the appropriate therapy. The use of water enema and complete distention of the rectum are reliable techniques for improving the accuracy of CT in the assessment of local invasion by cancer. PMID- 2217795 TI - Intrahepatic portal venous system: variations demonstrated with duplex and color Doppler US. AB - Seventeen cases of variations of the intrahepatic portal venous system were investigated with use of duplex and color Doppler ultrasound (US). Seven cases involved absence of the horizontal segment of the left portal vein, with portal supply to the left lobe arising from the right lobe. The 10 remaining cases involved variations of intrahepatic portal branching resulting from absence of the right portal vein, taking four patterns. It is thought that these findings represent variants of normal. These variants are important in two settings: in planning hepatic surgery and in the differential diagnosis of chronic portal vein thrombosis. PMID- 2217796 TI - Cardiac and vascular imaging with an MR snapshot technique. AB - Real-time vascular and cardiac magnetic resonance (MR) imaging has been reported only with echo-planar imaging. In this study, the fast low-angle shot (FLASH) MR imaging sequence was reduced to repetition times of 3 msec and echo times of less than 1.3 msec with use of an improved MR imaging system. The resulting 200-msec MR images (64 X 128 pixels) are called snapshot FLASH images. They allow measurements from dynamic series of MR images depicting processes such as relaxation behavior and the cardiac cycle in the absence of motion and flow artifacts. In animal studies (at 4.7 T) and in studies of human volunteers (at 2.0 T), vascular and cardiac snapshot FLASH images were obtained as a single shot, as reconstructed motion, and as real-time movies. The arbitrary and fast T1 contrast of these images and the reduction of motion artifacts result in favorable applications for the depiction of myocardial and great-vessel anatomy. These clinical applications can be performed on conventional MR imagers with minor technical modifications. PMID- 2217797 TI - Vena caval flow: assessment with cine MR velocity mapping. AB - The authors used cine magnetic resonance (MR) velocity mapping to study flow in the superior vena cava (SVC) and inferior vena cava (IVC) of 13 healthy control subjects and 13 patients with right-sided cardiac disease. In the control subjects, peaks of flow in systole and diastole were observed, and mean SVC flow was 35% of the cardiac output. Respiratory gating was used in six control subjects to acquire images at end inspiration and end expiration, and although the systolic peak was reduced at end expiration, total flow was unchanged. A reduced systolic peak and retrograde flow in the IVC were observed in patients with tricuspid regurgitation. A reduced diastolic peak was seen in patients with pulmonary hypertension, pericardial constriction, and right ventricular dysplasia, reflecting reduced diastolic compliance of the right ventricle. In the patient with obstruction of the SVC, absence of flow was confirmed, and retrograde flow was seen in the azygos vein. The authors believe that cine MR velocity mapping is a reliable method of studying vena caval flow noninvasively and that it has important potential applications for the investigation of disorders of the right side of the heart. PMID- 2217798 TI - Evolution of deep venous thrombosis: a prospective evaluation with US. AB - Forty-six patients with a diagnosis of acute deep venous thrombosis (DVT) established by means of duplex ultrasound (US) were prospectively followed up with serial duplex US examinations during a 6-month period to assess the persistence of venous abnormalities. All patients were asymptomatic. Isolated popliteal DVT was found to be more likely to revert to normal at duplex compression US than thrombosis involving both the femoral and popliteal systems (P less than .05). Increased venous diameter was a sign of acute clot (P less than .005). Clot echogenicity did not help to enable distinction of acute DVT and chronic DVT. At compression US, 10 of 21 patients (48%) who initially had occlusive thrombosis had persistent abnormalities that mimicked findings consistent with acute DVT. Chronic venous changes that persisted after 6 months consisted of either lumen recanalization (with resultant intimal thickening) or persistent venous occlusion. Both of these conditions can result in incomplete compression, the major US indication of acute DVT. This appearance should not be confused with that of acute DVT. Follow-up examinations to establish a baseline appearance can be obtained as early as 6 months after an acute episode of DVT. PMID- 2217799 TI - Renal artery stenosis in patients with aortic dissection: increased prevalence. AB - The authors retrospectively analyzed the prevalence of renal artery stenosis in 63 consecutive patients with aortic dissection who underwent thoracic and abdominal aortography. Ten patients (16%) had renal artery stenosis, five with atherosclerosis and five with fibromuscular lesions. Risk factors for aortic dissection were Marfan disease in nine patients, bicuspid aortic valve in one, and hypertension in 54 (including seven patients with Marfan syndrome). If the patients with Marfan syndrome and the patient with the bicuspid aortic valve are excluded, renal artery stenosis was present in 10 of 53 patients (19%) when the cause of dissection was presumably hypertension. This finding suggests that renovascular hypertension is a greater risk factor for aortic dissection than is essential hypertension. The success of angiotensin converting enzyme inhibitors and percutaneous transluminal renal angioplasty (PTRA) in controlling renovascular hypertension has been proved. In this series, emergent PTRA successfully controlled the hypertension in one patient with a type B dissection, resulting in an excellent clinical outcome. Angiography should be routinely performed on patients with aortic dissections to evaluate for renal artery stenosis. PMID- 2217800 TI - Therapeutic embolization: enhanced radiolabeled monitoring. AB - Radiolabeling of Ivalon (polyvinyl alcohol sponge) particles permits localization of injected particles during embolization through the use of a portable gamma camera and provides a means to prevent potentially fatal complications such as pulmonary embolization. A more efficient technique of labeling Ivalon particles with technetium-99m sulfur colloid was developed. An increase in labeling efficiency allowed more accurate determination of the distribution of injected Ivalon particles. Scanning electron microscopy demonstrated the stability of the Ivalon particles during this new labeling process. Two patients with arteriovenous malformations underwent therapeutic embolization with radiolabeled Ivalon particles; gamma camera imaging of the lesion and chest was performed throughout the procedure. PMID- 2217801 TI - MR imaging of the bird's nest filter. AB - The appearance of the Bird's Nest inferior vena cava filter on magnetic resonance (MR) images of 11 patients is described. No complication or symptomatic filter displacement was encountered as a result of MR imaging performed at 1.5 T. The filters created significant local artifact and distortion on MR images. However, diagnostic MR images of the pelvis, spine, and brain may still be obtained. PMID- 2217802 TI - Irrigation device for neuroangiographic procedures. AB - A simple irrigation device for use in diagnostic and interventional neuroangiographic procedures is described. The device is used to flush bubbles and blood clots from catheter hubs. The authors also describe a technique in which this device can be used to prevent filling a catheter with air when a guide wire is removed. PMID- 2217803 TI - Synovial membrane: percutaneous biopsy. AB - With use of fluoroscopy, new techniques of percutaneous synovial biopsy (PSB) of large joints of limbs (other than the knee) were developed. PSB was performed on outpatients with the use of local anesthesia. Eighty-four biopsies (hip, 57; shoulder, 10; elbow, six; wrist, five; and ankle, six) were performed. With experience, modifications evolved in the PSB technique. The main technical refinements were use of a Tru-Cut needle introduced through a Jamshidi trephine needle, placement of the cutting window parallel to the anterior aspect of the joint, and selection of an optimal approach and biopsy site. With these improvements, the success rate for obtaining synovial membrane was raised from 48% to 81%. No complications were encountered. PMID- 2217804 TI - Performance of quality assurance audits by students. PMID- 2217805 TI - Monitoring sedated pediatric patients during MR imaging. PMID- 2217806 TI - Patient confidentiality in radiology. PMID- 2217807 TI - Professional quality assurance for mammography screening programs. PMID- 2217808 TI - Nonsurgical fallopian tube recanalization for treatment of infertility. PMID- 2217809 TI - Cervical myelography. PMID- 2217810 TI - Sisera's death: an afterword. PMID- 2217811 TI - 76th scientific assembly and annual meeting: Radiological Society of North America including sessions in joint sponsorship with the American Association of Physicists in Medicine. November 25-30, Chicago. Abstracts. PMID- 2217812 TI - Nurse makes "anonymous call": freedom of speech. PMID- 2217813 TI - Doctor "did not know what he was doing": death results. Case in point: Robinson v. Kaiser Foundation Hosps. (269 Cal. Rptr. 468--CA 1990). PMID- 2217814 TI - Legal case briefs for nurses. MI.: "at will" employment: termination for cause; CA.: nurse blows whistle: Dr.'s privileges suspended. PMID- 2217815 TI - Nurse orders objecting patient to "shut up". Case in point: Roberson v. Provident House (559 So. 2d 838--LA (1990)). PMID- 2217816 TI - Nurse resigns over urine specimen issue. PMID- 2217817 TI - Is there a nurse-patient privilege? Case in point: Roberson by Isaac v. Liu (555 N.E. 2d 999--IL (1990)). PMID- 2217818 TI - Legal case briefs for nurses. GA.: nursing home supervision: negligence or malpractice? TN.: student challenges "grades admissions policy". PMID- 2217819 TI - The agency nurse: employee or independent contractor? Case in point: trauma nurses v. Board of Review (576 A. 2d 285--NJ (1990)). PMID- 2217820 TI - Axotomy-induced alterations in the electrophysiological characteristics of neurons. AB - The electrophysiological alterations provoked by axotomy have now been studied for almost half a century, in a number of different cell types. Consequently, it is now possible to detail some common mechanisms underlying these changes and to sort out certain trends in the data. The major phenomena reviewed in this section and some possible future directions are summarized below. (1) It is now possible to advance a unified hypothesis for the effects of axotomy on the conduction velocity of myelinated fibers. The key is that axon diameter, which is directly correlated with conduction velocity, is regulated, at least in part, by neurofilament protein gene expression and transport into the axon. Thus, the largest myelinated axons, with the fastest conduction velocities, have the highest neurofilament contents, and in turn, experience greater or faster declines in neurofilament content, axon caliber, and conduction speed following nerve injury. This regulation of neurofilament gene expression also appears to be target- and/or accessory cell-dependent. In fact, Hoffman and colleagues (1988) have hypothesized that neuron interactions with specific targets (via as yet unknown target-induced signals) may either specify or permit specification of the level of neurofilament gene expression in neurons. Imposed on this primary size determinant is an influence of activity, which also underlies the differential atrophy and decrement in conduction velocity exhibited by motor and sensory fibers of comparable diameters in the same lesioned nerve. Unmyelinated axons, whose structures are not dominated by neurofilament content and metabolism, react very differently to axotomy. The structural and metabolic basis of their reaction is not known. (2) Passive membrane properties, in particular neuronal input resistance, remain relatively stable in the majority of neurons after axotomy. The major exceptions, vertebrate spinal motoneurons, lamprey dorsal interneurons, and mammalian vagal motoneurons, all show an increase in input resistance after axotomy. This change in input resistance appears to be correlated with structural or geometric simplification of dendritic trees and real or apparent changes in specific membrane resistance in one case and with a reduction in cell body size in the other two; however, changes in specific membrane resistance cannot be excluded even in the latter two cases. In the spinal motoneurons, input resistance changes may be more pronounced in those neurons with the most extensive or complex dendritic geometries (i.e. F-type motoneurons). More combined electrophysiological (ideally under voltage or patch clamp conditions) and morphological investigations of single neurons need be done to resolve these questions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2217821 TI - The effects of antihypertensive drugs on the cerebral blood flow and its regulation. PMID- 2217822 TI - Pharmacologically active pyridazine derivatives. Part 1. PMID- 2217823 TI - Medicinal chemistry of 1-benzazepines. PMID- 2217824 TI - Peptide regulation of mast-cell function. PMID- 2217825 TI - Biological effects of mercuric chloride, nickel sulphate and nickel chloride. PMID- 2217826 TI - The fluoroquinolone antibacterial agents. AB - In summary, the last decade has been a highly fertile and productive period in quinolone medicinal chemistry, resulting in major improvements in potency, antibacterial spectra, oral absorption and pharmacokinetic properties as well as an increased knowledge of the molecular features important to conferring these various properties. Very recent discoveries concerning replacements for the 3 carboxylic acid moiety, previously thought to be uniquely essential for activity, to give highly potent antibacterials such as (83) illustrate the potential for new breakthroughs in this field. Among the major goals for future research remains the understanding of the potential cartilage toxicity associated with this class of agents, such that an agent useful for pediatric indications may be developed. Future studies can also be expected to further enhance and refine the level of current insight into the manner by which these agents inhibit the target enzyme on a molecular level. PMID- 2217827 TI - Developments in the antiemetic area: chemistry, pharmacology and therapy. PMID- 2217828 TI - Antagonists of platelet-activating factor: chemistry, pharmacology and clinical applications. PMID- 2217829 TI - Photodecomposition of drugs. PMID- 2217830 TI - Prostaglandin E2 and gestational hypotension in rabbits. AB - Arterial levels of 13,14-dihydro-15-keto-PGE2 (PGE2-M), a stable metabolite of prostaglandin E2 (PGE2) were compared between unanesthetized pregnant (n = 12) and nonpregnant (n = 8) rabbits with the aim of elucidating the role PGE2 in the development of physiological hypotension associated with pregnancy. On the 20th and 22nd days of the 30 day gestation period the mean arterial concentrations of PGE2-M were about 10-times higher (p less than 0.05) and largely variable as compared to that of nonpregnant rabbits. Mean arterial pressure was not lower on either the 20th (69 +/- 4 mmHg, mean +/- SD) or the 22nd (70 +/- 3 mmHg) days of gestation (dg) than in nonpregnant rabbits (69 +/- 4 and 73 +/- 6 mmHg, respectively). On the 23rd dg hypotension was invariably present (61 +/- 5 mmHg vs 72 +/- 4 in nonpregnants, p less than 0.001), but arterial levels of PGE2-M (31.0 +/- 31.6 ng/ml) did not overcome those measured on earlier, normotensive days of gestation. Hypotension was also evident in a subgroup of pregnant rabbits (n = 4) with low PGE2-M concentrations in the nonpregnant range (3.2 +/- 1.5 ng/ml vs 1.9 +/- 1.2 in nonpregnant rabbits, ns). Since the arterial level of PGE2-M proved to correlate (p less than 0.001) with both the uteroplacental venous and renal venous PGE2 concentrations, we suggest that a key role of uteroplacental and renal PGE2 played in the development of gestational hypotension is not probable in rabbits. PMID- 2217831 TI - A preliminary double-blind cross-over trial of lipo-PGI2, a prostacyclin derivative incorporated in lipid microspheres, in cerebral infarction. AB - Lipo-PGI2 is a drug preparation of a PGI2 analogue (isocarbacyclin methylester) which is incorporated into lipid microspheres with a diameter of 0.2 mu. Lipo PGI2 has been shown to accumulate at the vascular wall, particularly those of arteriosclerotic lesions, and it has a much stronger inhibitory activity on platelet aggregation than free isocarbacyclin. In this study, a preliminary double-blind cross over trial of lipo-PGI2 in cerebral infarction was carried out. Seventeen patients with chronic cerebral infarction received 2 micrograms of lipo-PGI2 and placebo daily for one week each in a cross-over double blind test. A significant improvement was noted for lipo-PGI2 compared with placebo in the overall improvement in neurological and mental symptoms (p less than 0.01). The patient's preference also indicated the effectiveness of lipo-PGI2 (p less than 0.05). Adverse reactions were noted in 3 patients receiving placebo, but not in any receiving lipo-PGI2. These results show that lipo-PGI2 at a very low dose would be beneficial as a treatment for relieving the clinical symptoms of chronic cerebral infarction and that lipid microspheres are a useful drug carrier for PGI2 analogue therapy. PMID- 2217833 TI - Electrophilic levuglandin E2-protein adducts bind glycine: a model for protein crosslinking. AB - Prevention by glycine of protein crosslinking which accompanies binding of levuglandin E2 (LGE2) is shown to involve binding of glycine with the protein LGE2 adduct. With ovalbumin, the LGE2 adduct initially binds nearly 2 equivalents of glycine, but the capacity to bind glycine decreases with time reflecting a competition, inter alia, with crosslinking. PMID- 2217832 TI - Common bile ligation in the rabbit: an appropriate model for investigating the relationship of endogenous gallbladder prostanoid synthesis with evolving acute inflammation. AB - Gallbladder prostanoid (PG) synthesis and histologic inflammatory changes were compared after 6, 24, and 72 hours of bile duct ligation (BDL) or cystic duct ligation (CDL) in the male rabbit. At each time interval the gallbladder was scored for degree of acute inflammation, examined by radiochromatography for endogenous PG synthesis and analyzed by ANOVA. BDL induced progressive increases in acute inflammation whereas prostanoid synthesis significantly increased only after the 6 and 72 hour groups. Indomethacin treatment inhibited PG synthesis in all BDL groups but only decreased the inflammation score in the 6 and 24 hour BDL groups. CDL did not induce progressive gallbladder inflammatory changes or prostanoid synthesis. These data show that prostanoids are intimately involved with the development of early acute gallbladder inflammation following BDL. Inhibition of PG synthesis could attenuate or retard the progression of early acute gallbladder inflammation if started prior to development of established disease. PMID- 2217834 TI - [Differential diagnosis of allergic and non-allergic dermatitis by measuring the levels of acid phosphatase in neutrophils and peripheral blood lymphocytes]. AB - Using the cytoenzymatic method acid phosphatase was determined in peripheral blood neutrophils and lymphocytes in 25 patients with allergic eczema, 31 patients with eczema due to irritants and 18 clinically healthy subjects. In patients with allergic eczema the percent of neutrophils and lymphocytes containing acid phosphatase was decreased and the activity of this enzyme in neutrophils was reduced. In patients with non allergic eczema these values were normal. The method of determination of acid phosphate in neutrophils and lymphocytes is regarded as useful for the differentiation between both types of eczema. PMID- 2217835 TI - [Fungal flora in mycoses among the population of the south-eastern Poland 1978 1988]. AB - In the years 1978-1988 a group of 2257 subjects was examined for the presence of fungal infection. In 785 cases positive results of cultures were obtained yielding 468 dermatophytes (60.1%) and 317 yeast-like fungi (39.9%). The most frequently isolated fungi were: Candida albicans (27.3%), Trichophyton mentagrophytes v. interdigitale (27.0%) and Trichophyton rubrum (20.6%). In the subgroup of dermatophytes anthropophilic fungi accounted for 87.5%. PMID- 2217836 TI - [Microsporum infection in patients treated at the Dermatological Clinic, Medical Academy, in Gdansk 1984-1988]. AB - In the years 1984-1988 in the Department of Dermatology, M. A. in Gdansk 80 cases of microsporum mycoses were diagnosed. The cases were due to Microsporum canis. Among 80 cases of this mycosis we found 59 children aged from 2 to 15 years and 21 subjects aged over 15 years. In children the most cases were diagnosed in the age group 4-7 years. In 40 cases (50%). M. canis produced lesions of hairless skin and in 36 cases (45%) the scalp was involved. PMID- 2217837 TI - [Incidence and enzymatic properties of yeast-like fungi. Examination of workers of various departments of the District Meat-Processing Industry in Bialystok]. AB - In a group of 111 workers of the District Meat Processing Plant clinical examination of the skin and cultures for Candida organisms were performed. The proteolytic and lipolytic properties of these fungi were analysed. From the interdigital spaces of hands 42 strains were isolated, with the species Candida albicans accounting for 13.5% of the strains (15). Case history and the character of skin lesions on the hands and forearms suggested that they were caused by skin contact with meat and internal organs producing the so called "gut eczema" while Candida was secondary agent causing exacerbation of skin changes. PMID- 2217838 TI - [Sensitivity and specificity of the Chlamydiazyme test in comparison with tissue culture in the light of our studies]. AB - The Chlamydiazyme Test was used in the laboratory examination of 1139 patients (716 women, 368 men, 55 children) hospitalized in the departments of urology, nephrology and gynaecology. Urethral and cervical smears were examined. In comparison with the culture method for C. trachomatis on McCoy cells the Chlamydiazyme test had a 91.6% agreement of the positive and negative results. The disagreeing results, that is only Chlamydiazyme test positive or only culture positive, accounted respectively for 2.1% and 6.2% of the results. The sensitivity of the Chlamydiazyme test was 74.6% and its specificity was 97.2%. PMID- 2217839 TI - [Eosinophilic pustular folliculitis (Ofuji)]. AB - A case of eosinophilic pustular folliculitis is described. The patient was a man aged 28 years with typical clinical and histological findings. The disease developed after an insect sting. Evident improvement was obtained after administration of sulphones with corticosteroids. PMID- 2217840 TI - [Results of desensitization using household dust mite in patients with atopic dermatitis]. AB - The HDM vaccine Bencard of housedust mite was used for desensitization by generally used methods of 17 patients with atopic dermatitis. Very good improvement was achieved in 6 cases, medium improvement in 10, and no improvement in 1 case. The possible role of psychogenic factors in this improvement is discussed. PMID- 2217842 TI - [Results of 5-day ofloxacin (Tarivid) treatment of chlamydial urethritis in men]. AB - The examined group of men with urethritis comprises 40 patients at age 20-50 yrs. Diagnosis of Chlamydia trachomatis infection was based on the positive results of two of three techniques: culture on McCoy cells, direct immunofluorescent (Chlamyset) and immunoenzymatic (Chlamydiazyme) methods. The patients with CT urethritis were treated with Tarivid given orally 2 X 200 mg daily for 5 days. Five days later they were reexamined with the same methods. The results were as follows: 36 out of 40 patients were negative by culture and Chlamydiazyme and were clinically cured. Four were positive by both methods and still had symptoms of urethritis. PMID- 2217841 TI - [Evaluation of the methods of treatment of epithelioma basocellulare at the I Dermatology Clinic, Silesian Medical Academy, in Katowice]. AB - The therapeutic results are presented in cases of basocellular epithelioma treated by three methods. The best and most radical results were obtained by the surgical method, followed in the order of effectiveness by radiotherapy (45-55 kV) in a total dose of 4500-6000 R. In case of contraindications to these methods local chemotherapy was applied which was associated with a high proportion of failures (28.6%). PMID- 2217843 TI - [Treatment of head pediculosis. Comparative studies of a shampoo containing 0,33% Pyrethrum extract and shampoo containing 1% malathion]. AB - The insecticidal effect was tested of a shampoo with 0.33% of pyrethrum extract and a shampoo with 1% malathion. The study was carried out in 222 patients and better results were observed with the pyrethrum shampoo which required only one application. PMID- 2217844 TI - [General-action antifungal drugs--trends in their development and use]. PMID- 2217845 TI - [Changes in various apolipoprotein levels in psoriasis]. AB - In 104 patients with common psoriasis the patterns of apolipoproteins A and B were studied in serum depending on the course of the disease, extent of skin changes and infection preceding the appearance of eruptions. The highest concentrations of apo A and apo B were found in the group with generalized psoriatic changes independent of the activity of the disease. PMID- 2217846 TI - [Staging the psychoanalytic situation in supervision]. AB - Fantasies, parapraxes, and associations that figure significantly in the transference-countertransference process between patient and analytic candidate also work their way into the relationship between the candidate and the supervisor--sometimes in disguised fashion. The author illustrates this observation with vignettes and shows how, with the help of Lorenzer's concept of scenic understanding, the interaction pattern observable in the supervision can be utilized for the understanding of the material presented by the patient. PMID- 2217848 TI - [Reclaiming the feeling of shame]. AB - The author resorts to Bleger's conception of regression to ambiguity in order to achieve an understanding of patients who have suffered from extreme situations such as torture, disappearance, concentration camp. The regression to ambiguity that helped these patients to survive and that elicits extreme feelings of shame must be gradually diminished so that older intact ego components as well as the original feelings of shame can be reclaimed. PMID- 2217847 TI - [Ego and narcissism theory between 1914 and 1922 as it appears in the International Journal of Medical Psychoanalysis]. AB - The publication of Freud's essay on narcissism in 1914 set off a discussion about the psychoanalytic concepts of the ego and of narcissism. The author reviews this discussion by reference to articles appearing in the Int. Z. arztl. Psa. between 1914 and 1922. She highlights the theoretical and technical modifications corresponding to this discussion and demonstrates that apparently modern theories of the ego and of narcissism have their roots largely in that period. PMID- 2217849 TI - [Edgar Degas, photography and voyeurism]. AB - Degas has drawn his paintings in a voyeuristic perspective. This voyeurism is not due to the painter's personal psychopathology. Instead, Degas has recognized the voyeuristic change of visual perception as a result of the development of photography as a new medium; meanwhile this change has become unconscious. Degas' paintings thus confront us with the historicity of visual perception and of the visual partial instinct. PMID- 2217850 TI - [Those who praise me..., those who fault me...D. E. Zimmer, H. Platta and psychoanalysis]. PMID- 2217851 TI - [Selected problems of diagnosis, natural course and prognostic significance of borderline arterial hypertension. III. Long-term studies of borderline hypertension in children and adolescents]. AB - Cardiological reevaluation was carried out in a group of subjects aged 19-28 years in whom elevated (n = 80) or normal blood pressure (n = 69) had been found 10 years earlier. Control physical examination was extend to 24 hour ambulatory blood pressure monitoring. In both groups differences in systolic and diastolic blood pressure levels after 10 years are characterized by significant (p less than 0.001) negative correlation with its initial values. Elevated blood pressure (greater than 140/90 mmHg) was found in 21 patients of the studied group (23.3%) and in 4 controls (5.8%, p less than 0.001). The results of blood pressure monitoring are in accordance with traditional measurements and confirm equalization of mean blood pressure values, maintenance of group differences in diastolic pressure and correctness of diagnosis (at 10 years) of borderline or mild arterial hypertension. Complaints reported by the patients as well as ECG studies do not suffice for verification of young persons with elevated blood pressure and risk of hypertension. In this respect it is more useful to repeat measurements by using continuous automatic recording devices although considerable variations in blood pressure levels in longterm observations in young subjects indicate the need of careful prognosis concerning evolution of the disease. PMID- 2217852 TI - [Selected problems of diagnosis, natural course and prognostic significance of borderline arterial hypertension. IV. Evaluation of the usefulness of diagnostic methods]. AB - In 80 subjects, aged 19-28 years with elevated blood pressure 10 years earlier, compared with a group of normotensives (n = 69) family history of hypertension and the results of echocardiography, dynamic exercise stress testing and cold pressor test were evaluated. Pathogenic role of family history was shown by the diagnosis of arterial hypertension in 84% of the parents of children and adolescents with initially elevated blood pressure. The effects of elevated blood pressure on its further course are confirmed by the incidence of borderline hypertension in 26.3% of the studied group as compared with 5.8% of the controls. The patients with elevated blood pressure were characterized by hyperkinetic cardiac state manifested by a significantly higher heart rate, higher ejection fraction and cardiac output. The results of bicycle exercise test and cold pressor tet proved useless in the prognosis. However, despite the lack of prognostic value it was found that in studied population an exercise induced rise of systolic blood pressure correlated with echocardiographic parameters of cardiac size and mass. Similarly a positive correlation was found between the highest blood pressure during exercise and left ventricular mass in patients with borderline hypertension. The studies showed prognostic difficulties in the early stage of primary hypertension emphasizing the usefulness of modern methods providing an insight into the state of labile at that age cardiovascular system. PMID- 2217853 TI - [Acetylation phenotype as a risk factor of diabetic neuropathy]. AB - Acetylation phenotype was determined in 184 diabetics: 102 patients with Type I (insulin-dependent) and 82 patients with Type II (non-insulin-dependent) diabetes mellitus, who underwent complex investigations to assess the development of sensorimotor and autonomic neuropathy. The control group consisted of 121 healthy subjects of the same age distribution. The results obtained imply that the slow acetylation phenotype may be considered as a significant risk factor of diabetic neuropathy. PMID- 2217854 TI - [Effect of alcohol on the lymphocyte system. V. Evaluation of blast transformation and rosette formation of peripheral blood lymphocytes in alcoholics]. AB - Transformation and rosette formation of peripheral blood lymphocytes were studied. We have observed decrease in lymphocyte response to the mitogen as well as in spontaneous ability to the transformation. The percent of B-rosettes was diminished, while T-rosettes were in normal ranges. Lower index of completely transformed ones in men indulged to freely in alcohol may be consequence of altered cell membrane fluidity of shifts in T lymphocyte subpopulations. PMID- 2217855 TI - [Clinical and electrophysiological studies of the organ of hearing of newborn infants. III. Evaluation of the organ of hearing of newborn infants from high risk pregnancy using brain stem evoked response audiometry (ABR)]. AB - In a group of 130 tested newborns, pathological brain stem responses derived from acoustic stimulus was achieved in 28 cases (21.5%). 85.2% of newborns in this group of birthed babies comprised a high-risk pregnancy group. Based on criteria evaluating monitoring and parameters achieved ABR responses: conduction hearing disorders were found in 7 newborns, sensori-neural in 12 cases, and neurological dysfunction was observed in 9 cases. Control testing was carried through for three months following the initial evaluation allowing for the elimination of 12 children in a group of 19 for further testing and observation. This represents 42.85% of children initially evaluated as possessing a hearing disorder and 9.2% from the total of those tested. Results obtained during successive control testing were carried-out in a 3-6 month period following the initial examination and allowed for decisions to be made. Conforming to: 4 children (3.07%) were supplied with hearing aids and hearing rehabilitation begun, 1 child (0.76%) was referred to rehabilitation the deaf, whereas the 2 remaining children (1.53%) are currently under neurological observation. Nonetheless, testing older children eliminates cases that present with lack of success at the initial evaluation or transitory hearing impairment that is self-limited, although ABR testing, while the child is on the unit, allows for the introduction of hearing-organ controls of newborns based on population testing. PMID- 2217856 TI - [Natural defense mechanisms of the respiratory tract in the otolaryngological aspect]. PMID- 2217857 TI - [Use of impedance plethysmography in the studies of cardiac function]. PMID- 2217858 TI - [Medical experiments on humans and Purkinje's self-observations]. PMID- 2217859 TI - [Myasthenic reaction in polymyositis]. PMID- 2217860 TI - [Dr. Franciszek Mehrer, a prominent Lvov urologist in the inter-war period]. PMID- 2217861 TI - Clinical evaluation of digital TV tomography. AB - A unit for digital TV tomography (DTT) was constructed on the basis of retrospective reconstruction of digital data acquired during a linear tomographic motion of an X-ray tube and an image intensifier with a television camera (I.I. TV) assembly. Following descriptions of the basic principle and system, clinical results obtained with this unit are presented. Comparison with conventional tomography of the chest, skull, abdomen, and bones and joints showed equal diagnostic information in more than 50% of cases. Application to intra-arterial and intravenous DSA provided excellent images, but no new information was obtained. DTT has the advantages of technical simplicity, short examination time, low exposure dose, and compatibility with a PACS system. This technique will become an important part of a modern radiology department. PMID- 2217862 TI - Radiological findings of vanishing tumor of the stomach. AB - Four lesions in three patients with so-called vanishing tumor of the stomach are described. Two patients had one lesion each and the third patient two lesions. The lesions were localized in the gastric cardia, angle, and antrum. Radiological findings of these tumors showed a round tumor with smooth surface and regular margins. The edges of the tumors were gently sloping, while the mucosa surrounding the tumor was edematous. The time interval until these tumors disappeared was five days, 20 months, 12 months and seven months, respectively. When the soft appearance of a gastric tumor is suspected in UGI examination, the patient should be re-examined after a month or more, to avoid unnecessary surgery. PMID- 2217863 TI - Computerized three-dimensional normal atlas. AB - This paper presents our ongoing project in which normal human anatomy and its quantitative data are systematically arranged in a computer. The final product, the Computerized Three-Dimensional Normal Atlas, will be able to supply tomographic images in any direction, 3-D images, and coded information on organs, e.g., anatomical names, CT numbers, and T1 and T2 values. PMID- 2217864 TI - Multiseptate gallbladder: computed tomographic appearance. AB - We report a case of multiseptate gallbladder in a 43-year-old female with ultrasonographic and computed tomographic (CT) findings. The postcontrast CT delineated multiple septations with honeycomb appearance in the gallbladder. This finding should raise the suspicion of multiseptate gallbladder. PMID- 2217865 TI - Asymptomatic Bochdalek hernia diagnosed by magnetic resonance imaging. AB - An asymptomatic mass at the base of the left lung was examined by computed tomography (CT) and magnetic resonance (MR) imaging. Coronal and sagittal T1 weighted MR images provided a definitive diagnosis of Bochdalek hernia. PMID- 2217867 TI - Management of malignant thymoma. AB - Six cases of malignant thymoma were treated by various methods, i.e., surgery, radiotherapy and chemotherapy. The combination of surgery and radiotherapy seems to be the most effective method of treatment. Histology does not seem to influence survival. PMID- 2217866 TI - Bone mineral density of the lumbar spine by dual photon absorptiometry: age related regression in normal Japanese subjects and fracture threshold in osteoporotics. AB - The bone mineral density (BMD) of the lumbar spine was determined by DPA in 280 normal Japanese volunteers and 11 osteoporotic women with compression fractures. In women, bone loss started from the mid thirties and accelerated after the age of 50 years at the rate of 0.75% (0.0074 g/cm2) per year. In men, bone loss started from the mid twenties and occurred linearly at the rate of 0.30% (0.0032 g/cm2). The overall diminutions in vertebral BMD throughout life in men and women were 13.0% and 24.3%, respectively. The mean vertebral BMD of the osteoporotic women with recent compression fractures was 37.5% lower than that of age-matched controls. The 90th percentile for vertebral BMD in this group was 0.584 g/cm2. By the age of 80 years, approximately one-fifth of normal Japanese women have BMD values less than this. PMID- 2217868 TI - The selection of patients for accelerated radiotherapy on the basis of tumor growth kinetics and intrinsic radiosensitivity. AB - Mathematical modeling was used to reach qualitative conclusions concerning the relative rate of local tumor control that might be achieved by using accelerated fractionation to treat only the patients with the most rapidly growing tumors, compared with the control rates that could be expected from either conventional or accelerated radiotherapy alone. The results suggest that concomitant boost therapy is equally or more effective than conventional dose fractionation for all tumors, regardless of their growth kinetics. For tumors with very short clonogen doubling times, CHART (continuous hyperfractionated accelerated radiotherapy) may be even more effective than concomitant boost treatment, but CHART is less effective than conventional or concomitant boost therapy for tumors with longer clonogen doubling times. Thus, there is a rationale for using a predictive assay of tumor clonogen doubling times to identify the patients who should be treated with CHART. However, improvements in local tumor control resulting from concomitant boost treatment or the selective use of CHART are not likely to be apparent in the population as a whole, because the overall control rates are largely determined by refractory tumors having little chance of control with any of the treatments and by highly responsive tumors that are likely to be controlled regardless of the treatment choice. Differences in control rates with different treatment strategies are most apparent in the stochastic fraction of the population, which excludes those patients for whom there is either very little chance (e.g. less than 1%) or a very high chance (e.g. greater than 99%) of achieving local control with both treatments. The stochastic fraction can be approximated by excluding those patients with the most radioresistant and the most radiosensitive tumors, since intrinsic tumor radiosensitivity appears to be the single most important factor determining treatment outcome. PMID- 2217869 TI - Radiation-induced brachial plexus injury: follow-up of two different fractionation schedules. AB - All 449 breast cancer patients treated with post-operative radiotherapy to the breast and lymph nodes between 1982 and 1984 have been followed for 3-5.5 years. In this group two different fractionation schedules were used, one five times a fortnight and one daily, both over 6 weeks. The calculated dose to the brachial plexus was 45 Gy in 15 fractions or 54 Gy in 30 fractions. These schedules are equivalent doses using the standard NSD formula. The diagnosis of a brachial plexus injury was made clinically and computed tomography was used to distinguish radiation injury from recurrent disease. The actuarial incidence of a radiation induced brachial plexus injury for the whole group was 4.9% at 5.5 years. No cases were seen in the first 10 months following radiotherapy. The incidence rises between 1 and 4 years and then starts to plateau. When the large fraction size group is compared with the small fraction size group the incidence at 5.5 years is 5.9% and 1.0%, respectively (p = 0.09). Two different treatment techniques were used in this group but were not found to contribute to the probability of developing a brachial plexus injury. It is suggested that radiation using large doses per fraction are less well tolerated by the brachial plexus than small doses per fraction; a commonly used fractionation schedule such as 45 Gy in 15 fractions may give unacceptably high brachial plexus morbidity; and the use of small doses per fraction or avoiding lymphatic irradiation is advocated. PMID- 2217870 TI - Treatment of extremity soft tissue sarcomas with surgery and radiotherapy. AB - The results of treatment with a combination of surgery and radiotherapy of 102 patients with nonmetastatic extremity soft tissue sarcoma are reported. Seventy nine patients were previously untreated and 23 had locally recurrent disease. Sixty-six tumours were situated in the lower limb and 16 in the limb girdles. Fifty-nine were high grade lesions, and 64 were over 5 cm in length. Surgical clearance was "good" (wide or radical) in only 34 cases. Sixty-eight patients received post-operative irradiation, 23 pre-operative irradiation and 11 both pre and post-operative radiotherapy. Seventeen patients subsequently developed local recurrence and 9 of these remain disease-free after further surgery. Actuarial 5 year local control and disease-free survival rates for new cases were 87 and 65.4%; and for previously recurrent cases these figures fell to 75 and 54.8%. Following a univariate analysis of patient, tumour, surgical and radiotherapeutic factors only previous local recurrence (p less than 0.1 greater than 0.05) was found to significantly increase the risk of further local relapse. Multivariate analysis found high tumour grade [relative risk (RR) 8.4], tumour size greater than 15 cm (RR 3.66), previous local recurrence (RR 6.47) and proximal site (RR 12.7) to be independent poor risk factors for survival. PMID- 2217871 TI - Methemoglobinemia induced by topical anesthetic (benzocaine). AB - Methemoglobinemia is a condition in which more than 2% of the hemoglobin of the blood has been oxidized to the ferric form, a molecule which is incapable of binding oxygen or carbon dioxide. Clinically, the patient appears lethargic, cyanotic, and does not respond to oxygen. We describe a patient with esophageal carcinoma who developed severe methoglobinemia following application of benzocaine in spray for local anesthesia prior to intraluminal irradiation. Review of the literature is presented. PMID- 2217873 TI - American way. PMID- 2217872 TI - Case #5. Dentigerous cyst. PMID- 2217874 TI - Who are the watchdogs? PMID- 2217875 TI - Panic attacks are real events. PMID- 2217876 TI - Quest for knowledge. PMID- 2217878 TI - Are your patients safe? PMID- 2217877 TI - Patient #3. Surmontil. PMID- 2217879 TI - Case #8. Periapical cyst. PMID- 2217880 TI - Hospital hygienists. PMID- 2217882 TI - Breaking away from the education log jam. PMID- 2217883 TI - Case #9. Squamous cell carcinoma. PMID- 2217881 TI - Assure quality patient care. PMID- 2217884 TI - All in the family. PMID- 2217885 TI - Determining what makes you happy. PMID- 2217886 TI - Duties and rights. PMID- 2217887 TI - Sterilization: the first choice. PMID- 2217888 TI - The right issues to tackle and win. PMID- 2217890 TI - Identification of inhibin and inhibin-related proteins in human follicular fluid. AB - Inhibin-related proteins were identified in human follicular fluid following fractionation by gel permeation chromatography under neutral and acidic conditions, reversed-phase high performance liquid chromatography (HPLC) and preparative polyacrylamide gel electrophoresis. A number of molecular mass forms of inhibin (30-36 and 59-66 kDa) based on their in vitro biological and immunological activities were identified, of which 59-66 kDa inhibin was the predominant form. Bioactive fractions devoid of inhibin immunoactivity were also identified with molecular masses of 46 and 55 kDa. Based on their retention positions on reversed-phase HPLC and their lack of inhibin immunoactivity, these proteins are likely to be follicle stimulating hormone (FSH) suppressing proteins/follistatins previously identified in bovine and porcine follicular fluids. In addition, an immunoactive inhibin fraction devoid of bioactivity was identified in large amounts in the 50-70 kDa region of the gel permeation chromatogram at neutral pH. This material, based on previous findings with the fractionation of bovine follicular fluid, is likely to be the alpha-inhibin subunit precursor protein. No FSH stimulating activity (activin) was identified in any of the chromatograms, suggesting that the levels of activin in human follicular fluid are low. In conclusion, inhibins of molecular mass 30, 36, 59 and 66 kDa have been identified in human follicular fluid. Proteins with inhibin bioactivity devoid of immunoactivity and vice versa have also been detected and these proteins are probably FSH suppressing protein and an alpha-inhibin subunit precursor protein. Activin could not be identified. PMID- 2217889 TI - A comparison of the effects of bilateral efferent duct ligation and of partial epididymectomy on the testes of rats. AB - Testis weight as a percentage of body weight did not change following bilateral ligation of the efferent ducts (EDL) close to the epididymis, whereas following removal of part of the epididymis between the site of ligation and a point close to the junction between the caput and corpus (PCE), testis weight first rose linearly until Day 4 and then showed an exponential decrease between Days 4 and 28. After EDL, the perimeter of the seminiferous tubules rose for the first 7 days and then remained elevated, whereas after PCE, there was a linear decrease between Days 4 and 28. Following EDL, the percentage of altered and degenerated tubular cross-sections rose to about 30% and 10%, respectively, during the first 7 days after operation and then remained constant; after PCE, the percentage of altered tubules reached a maximum of 54% by 4 days and then fell, whereas the percentage of degenerated tubules continued to rise to 95% by 28 days. It would appear that all the effects of removal of a portion of the epididymis cannot be explained by blockage of the excurrent ducts, and a specific endocrine effect of the epididymis on the testis is proposed. PMID- 2217891 TI - Effect of beta-endorphin on steroidogenesis by bovine luteal cells. AB - To determine if opioid peptides have a local effect on the modulation of progesterone (P4) synthesis, a study was made of the effect of beta-endorphin and leu-enkephalin on P4 production by pure preparations of small luteal cells and dissociated luteal cells comprising both small and large cells from cows 2-3 months pregnant. Corpora lutea were dispersed by collagenase, and the large and small luteal cells were separated using Percoll gradients. Viable luteal cells (5 x 10(5)) were incubated in 0.5 mL of Eagle medium for 2 h at 37 degrees C, in an atmosphere of 5% CO2. Cells were treated with 8-bromoadenosine 3',5' monophosphate (8Br-cAMP), hCG, beta-endorphin (BE) and leu-enkephalin (LE) alone or in combination. When small luteal cells were used, P4 synthesis was significantly enhanced in the presence of opioid peptides alone (P less than 0.01); there was an additive effect with 8Br-cAMP and with hCG. For dissociated luteal cells, opioid peptides alone had no effect on P4 production but the stimulation of P4 production induced by 8Br-cAMP or hCG was significantly (P less than 0.01) inhibited in the presence of opioid peptides. In contrast, dissociated luteal cells that were preincubated with PGF2 alpha (degranulation) responded to the presence of BE with increased P4 synthesis similar to that seen with the pure preparation of small luteal cells. It is concluded that opioid peptides play an auto/paracrine role in both basal and tropic hormone-induced stimulation of steroidogenesis by the bovine luteal cell. PMID- 2217892 TI - Maximum survival of frozen goat embryos is attained at the expanded, hatching and hatched blastocyst stages of development. AB - Embryos were collected 5, 6 and 7 days after ovulation to determine their optimum stage of development for cryopreservation. The embryos were frozen using either glycerol or dimethyl sulfoxide (DMSO) as cryoprotectant, and then thawed and cultured to determine their viability. The rate of survival increased as the stage of development of the embryos increased. All hatched blastocysts survived freezing regardless of which cryoprotectant was used, whereas none of the 22 morulae frozen with DMSO survived, and only 12 of the 63 morulae frozen with glycerol survived. At the early blastocyst stage there was a significantly different result between freezing procedures (P less than 0.05) with greater survival rates obtained using DMSO rather than glycerol. The viability of goat embryos obtained at the early to hatched blastocyst stages, when collected 7 days after ovulation, was assessed by transferring half the embryos singly to recipients and freezing the remainder before transfer. When pregnancy was tested at the 7th week of gestation, the survival rate of fresh embryos was 67/111 (60%) compared with 64/109 (59%) for frozen-thawed embryos. PMID- 2217893 TI - Salivary oestradiol and progesterone after in vitro fertilization and embryo transfer using different luteal support regimens. AB - Salivary oestradiol (E2) and progesterone (P) levels have been shown to reflect the biologically active fractions in the serum. The luteal-phase status of stimulated cycles was investigated after in vitro fertilization and embryo transfer (IVF-ET). Thirty patients were randomly allocated to one of three luteal therapy groups: group A had no support, group B had intramuscular P and group C had intramuscular P and human chorionic gonadotrophin (hCG). One pregnancy was achieved in group A, two in group B and three in group C. Significant correlations between salivary and serum levels of E2 and of P in matched samples during luteal phase were found. Salivary E2 levels from luteal day 8 through day 14 and P levels from day 3 through day 14 were significantly higher in the pregnant than in the nonpregnant cycles. Among the nonpregnant cycles, salivary E2 and P levels were significantly higher in group C than in group A or B. These findings suggest that, in stimulated cycles for IVF-ET, determination of salivary E2 and P levels may be used as reliable alternatives to serum concentrations for assessing the luteal phase. Also, the additional hCG has an enhanced luteotrophic effect, as reflected by the higher salivary E2 and P levels, which may lead to a better pregnancy rate. PMID- 2217894 TI - Granulocyte macrophage colony stimulating factor (GM-CSF) in the murine reproductive tract: stimulation by seminal factors. AB - The activity of GM-CSF during early pregnancy in the murine uterine lumen in vivo and in media conditioned by uterine cells in vitro has been assessed. GM-CSF was detected in uterine luminal fluid recovered by lavage on the morning after syngeneic mating (median level 5.7 CFUc U/uterus) and following mating with vasectomized (5.1 U/uterus) or allogeneic males (4.4 U/uterus), with significantly lesser (P less than 0.05) amounts recovered from the uteri of superovulated, mated mice. By contrast, GM-CSF was only detectable (greater than 0.5 U/uterus) in the luminal fluid of three of 22 unmated oestrous mice examined. No activity was detected in secretions from male accessory glands including seminal vesicle, epididymis, prostate and coagulating gland (less than 0.5 U/gland). GM-CSF was found at higher levels in supernatants from cell monolayers prepared by tryptic digest of the uteri of Day 1 mated mice than those from unmated oestrous mice (P less than 0.05). Little GM-CSF was detected in supernatants from ovariectomized mice. An alpha-GM-CSF polyvalent antibody neutralized the FD5/12 bioassay response confirming the identity of the lymphokine. The interleukins IL-2 and IL-3 were not detected in uterine luminal fluid nor in media conditioned by cell monolayers. We postulate that elevated uterine GM-CSF activity after mating is elicited by a non-sperm associated, non MHC component of the ejaculate and synthesized by a hormone-responsive endometrial cell population. This cytokine may have an embryotrophic role or contribute to priming of the uterus for implantation. PMID- 2217895 TI - Production of interspecies chimeric calves by aggregation of Bos indicus and Bos taurus demi-embryos. AB - Two experiments were conducted to produce interspecific chimeric calves by aggregation of B. indicus and B. taurus demi-embryos. In the first experiment, morulae, compacted morulae, and early blastocysts were collected nonsurgically from Brahman (B. indicus) and Friesian (B. taurus) donors. Embryos were bisected and one demi-embryo from each species was placed in a single zone pellucida. In the second experiment, Brahman (B. indicus) and Hereford-Shorthorn (HS) (B. taurus) demi-embryos were aggregated. The resulting 'chimeric embryos' were transferred nonsurgically to synchronous recipients immediately following microsurgery. Of 112 recipients of 112 chimeric embryos, 29 (26%) were pregnant at 60 days. Of these, 24 (83%) produced full-term calves and 5 (17%) aborted between 2 and 5 months' gestation. From the 24 full-term pregnancies, two sets of twins and 22 singleton calves were born. Of the 22 singletons, 15 were chimeric including six bull calves (one Brahman-Friesian and five Brahman-HS) that were overt chimeras. All the overt chimeras resulted from aggregation of halves of early morulae (precompaction). PMID- 2217896 TI - Effects of a monoclonal antibody against progesterone, on embryo transport, development and implantation in laboratory mice. AB - A monoclonal antibody against progesterone (11P27) given on Day 2 of pregnancy interrupted pregnancy in BALB/c mice but not in BCF1 mice. The reason for this strain difference remains unclear, although it may involve discrimination by the recipient's immune system. The effects in BALB/c mice were reversed by progestin treatment. A dose of 5 nmol, which completely blocked implantation, had no significant effects on embryo transport and development on Day 4. A dose of 10 nmol did not increase the proportion of abnormal embryos, even though it accelerated tubal transport and increased embryo loss. No tubal retention was evident; most remaining embryos reached the uterus at the normal time. The transformation of morulae to blastocysts was only slightly delayed in 11P27 treated mice, and transfer experiments showed no decrease in embryo viability. The antibody appeared to act by blocking actions of endogenous progesterone on the uterus: uteri of 11P27-treated mice failed to develop a decidual cell reaction to intrauterine oil, and embryos from untreated donors failed to implant in 11P27-treated recipients. Antagonism of progesterone by antibody treatment prevented implantation in BALB/c mice apparently by actions on the uterus rather than on the embryo. PMID- 2217898 TI - The ovarian hyperstimulation syndrome and in vitro fertilization--strategies for prevention and management. PMID- 2217897 TI - Preimplantation development in the streptozotocin-induced diabetic mouse. AB - Streptozotocin (STZ) was used to develop a diabetic mouse model in which to study the development of the preimplantation embryo. STZ doses of 0, 160, 190, 210 and 240 mg kg-1 were given; 190 mg kg-1 was found to be the most suitable as the standard diabetogenic dose, providing about 60% mice with plasma glucose greater than 20 mM. The STZ-diabetic mice responded to superovulation with 10 i.u. of gonadotrophin in the same manner as control mice, producing similar embryo numbers at 48 h, 72 h and 96 h post-hCG. Furthermore, the proportion of 2-cell embryos collected from STZ-diabetic mice which developed to blastocysts in vitro was similar to that of 2-cell embryos from control mice. The STZ-diabetic mouse model after superovulation thus produced normal early preimplantation embryos whose development can be examined in detail in a diabetic environment. PMID- 2217899 TI - Infusion of epidermal growth factor in mice: organ distribution and urinary excretion. AB - Anesthetized mice were infused into the tail vein with 7.5% mannitol in saline (0.1 ml/min for 60 min) alone or with EGF at 0.5 microgram/min. Urine was collected every 10 min starting 20 min after the beginning of the infusion and ending 20 min after its termination. EGF concentration in the serum of mice infused with EGF increased from the baseline level of 0.6 +/- 0.4 to 70.7 +/- 16.0 ng/ml at 80 min. Total excretion of EGF for 80 min was 117 +/- 49 ng with mannitol alone and 1916 +/- 420 ng (6.4% of the EGF infused) after mannitol with EGF. Serum and urine EGF was indistinguishable from the native mouse EGF by its radioimmunoassay and HPLC characteristics. Intact labeled EGF was also found in urine when mice were infused with 125I-EGF (1 x 10(6) cpm/ml) in mannitol. After 5 min infusion with 125I-EGF (6 x 10(6) cpm/ml in saline), more than 80% of the label was found in the liver and kidneys and more than 90% of it was intact EGF. However, 30 min after infusion more than 95% of the labeled EGF was degraded. We conclude that at least part of the urinary EGF in mice originates in blood and that liver and kidneys are the main organs of EGF degradation. PMID- 2217900 TI - Ontogeny of glucagon messenger RNA and encoded precursor in the rat intestine. AB - The ontogeny of proglucagon mRNA and encoded precursor was studied in rat intestine from day 11 of fetal gestation (E11) to maturity. The earliest time point for detection of proglucagon antigenic determinants by immunocytochemistry, and of proglucagon mRNA by in situ hybridization histochemistry, was day 14 of fetal gestation (E14), suggesting this time as the point of onset of intestinal proglucagon gene expression and mRNA translation. Between day 17 and 18 of gestation (E17 and E18) there was a significant 10 fold increase in intestinal L cell density, indicating that this time in gestation is one of increased L cell differentiation and/or proliferation. Proglucagon mRNA abundance in developing rat intestine showed a major 8 fold increase between E17 and E18. Similar magnitude of increases in L cell density and proglucagon mRNA abundance suggests that the increase in proglucagon mRNA abundance reflects an increase in L cell numbers rather than increases in proglucagon gene transcription or mRNA stability per cell. PMID- 2217901 TI - Comparative studies on the release of vasopressin and 7B2 from isolated hypothalami. AB - A new protein, 7B2, has been found in the anterior, intermediate and posterior pituitary and the hypothalamus. It has been previously suggested that 7B2 is synthesized in the hypothalamus and is transported to the posterior lobe in a similar way to vasopressin (AVP). We examined the in vitro release of AVP and 7B2, using rat hypothalami in a perifused column system. Membrane depolarization with KCl (56 mM) caused a marked stimulation of AVP release (from 116% to 263% above basal values). Release of 7B2 was also stimulated by potassium from 106% to 212% above basal values. Potassium pulses in calcium-free medium failed to release AVP or 7B2. Osmotic and cholinergic stimulation increased AVP secretion by 205% and 282% above basal values, respectively, but had no significant effect on 7B2 secretion. Chromatographic profiles of perifusion media revealed one immunoreactive 7B2 peak eluting at a coefficient of 0.34 corresponding to that of rat hypothalamic 7B2. Similarly AVP coeluted with AVP standard. Thus AVP and 7B2 are differentially released by cholinergic and osmotic stimuli in vitro. PMID- 2217902 TI - VIP-containing nerve fibres in the submandibular gland of the dog and protein secretion in vitro in response to VIP. AB - Previously, administration of VIP has been shown to elicit no flow of saliva from the submandibular gland of the dog. However, in the present study we found VIP to cause release of protein in vitro from canine submandibular gland tissue. Furthermore, VIP-containing nerve fibres were demonstrated in large numbers in association with acini. Thus, VIP may be involved in the nervous regulation of salivary protein secretion in the dog. PMID- 2217903 TI - Differential effects of neuropeptides on coeliac and superior mesenteric blood flows in conscious rats. AB - The effects on coeliac and superior mesenteric blood flows of intravenous bolus doses of arginine-8-vasopressin (0.7 and 7.0 pmol) porcine neuromedin U-25 (0.01 and 1.0 nmol), rat alpha-calcitonin gene-related peptide (0.05 and 0.5 nmol), bombesin (0.06 and 0.6 nmol), and rat corticotropin-releasing factor (1.0 and 5.0 nmol) were investigated in conscious, Long-Evans rats chronically instrumented with pulsed Doppler flow probes. The peptides investigated were chosen on the basis of the range (vasoconstrictor-vasodilator) of their effects on superior mesenteric blood flow. With the exception of rat corticotropin-releasing factor (which increased coeliac and superior mesenteric flows) all peptides caused directionally opposite changes in coeliac and superior mesenteric blood flows. The results are consistent with the proposition that endogenous neuropeptides could influence blood flows to different abdominal viscera selectively. PMID- 2217905 TI - Insulin inhibits lipolytic activity and degradation of beta-lipotropin in rabbit adipose tissue. AB - beta-Lipotropin, a pituitary peptide, is a potent stimulator of lipolysis in rabbit adipose tissue in vitro and in vivo. Insulin inhibited the beta-lipotropin (1-100 nM)-stimulated glycerol release from rabbit adipocytes and fat pads significantly at concentrations of 10 and 100 microM. Both these concentrations of insulin also decreased the degradation of beta-lipotropin in intact adipose tissue to the same extent as the lipolytic activity. Furthermore, insulin reduced the degradation of beta-lipotropin in rabbit adipose tissue homogenate. Like insulin, several lysosomotropic agents also decreased significantly the degradation and the lipolytic activity of beta-lipotropin. On the other hand, insulin-like growth factor I in lower concentrations (1-100 nM) did not effect degradation and lipolytic activity of beta-lipotropin in rabbit adipose tissue. Thus, a direct influence of insulin on lysosomal enzymes degrading beta lipotropin in rabbit adipose tissue can be suggested. PMID- 2217904 TI - Isolation and structures of xenopsin-related peptides from rat stomach, liver and brain. AB - Using radioimmunoassay for detection, a mammalian counterpart to amphibian xenopsin (XP) was isolated and sequenced from pepsin-treated extracts of three different rat tissues and shown to be H-Phe-His-Pro-Lys-Arg-Pro-Trp-Ile-Leu-OH. This peptide, which shares six of the eight residues in XP, existed primarily in large molecular form(s) in the rat from which it could be liberated by the enzyme, pepsin. The XP-related sequence was differentially distributed through tissues, with concentrations ranging from ca. 80 pmol/g in diaphragm and skeletal muscle to ca. 800 pmol/g in stomach, liver and intestine. Like XP, the mammalian peptide potently crossreacted in a radioreceptor assay for neurotensin. These results prove the existence of radioreceptor-active XP-related sequences in multiple tissues of the rat. PMID- 2217906 TI - Distribution of neuropeptide Y in the spinal cords of cat, dog, rat, man and pig. AB - Regional distribution of neuropeptide Y (NPY) in spinal cord, dorsal root ganglia (DRG) and peripheral nerves was quantitated in rat, cat, dog, pig, and man. Spinal cords were harvested post mortem and dissected into regions or individual segments. A further dissection into dorsal and ventral horns was carried out, and DRG were harvested in all species except rat. Tissues were extracted into boiling 0.1 M HCl, and NPY was measured by radioimmunoassay using a specific antibody and I125-labeled NPY. Highest concentrations of NPY were consistently found in the dorsal horn of the lumbo-sacral cord (200-800 ng/g). DRG concentrations, in contrast, were routinely low or undetectable. Sciatic nerve concentrations in rat and pig were considerable. High performance liquid chromatography (HPLC) confirmed that the NPY immunoreactivity measured in dorsal horns of each species coeluted with authentic NPY (1-36) as a single peak. PMID- 2217908 TI - Effects of oxytocin on in vivo release of insulin and glucagon studied by microdialysis in the rat pancreas and autoradiographic evidence for [3H]oxytocin binding sites within the islets of Langerhans. AB - In the present investigation it was studied whether oxytocin administered directly in the pancreas of the rat stimulates the release of insulin and glucagon. In order to study such effects in vivo, a new experimental model applying the microdialysis technique was developed. To test the validity of the method, glucose or arginine were infused i.v. and it was shown that perfusate concentrations of insulin and glucagon increased significantly to 344 and 292% of basal overflow, respectively. Administration of oxytocin via the dialysis probe into the splenic portion of the pancreas resulted in significant elevations of insulin and glucagon concentrations to 210 (P less than 0.05) and 528% (P less than 0.01), respectively. The present study also includes a combined autoradiographic and immunohistochemical investigation of binding sites for oxytocin in the rat pancreas. A high density of [3H]oxytocin binding was present in the periphery of the islets of Langerhans, corresponding to the localization of the glucagon-producing alpha-cells. Both oxytocin and arginine(A)-vasopressin displaced [3H]oxytocin. The IC50 values were 10 and 180 nM, respectively. In conclusion, the oxytocin-induced release of insulin and glucagon as previously demonstrated in a number of species, may be due to a stimulation exerted by the peptide directly within the pancreas. PMID- 2217907 TI - The mechanism of action of bombesin on cat lower esophageal sphincter. AB - The effect of bombesin on the tone and the responses of strips from the lower esophageal sphincter (LES) to field electrical stimulation (FES) (2 Hz, 0.2 ms, supramaximal current intensity, 20 s duration) was studied. Bombesin dose dependently increased the LES tone. The threshold for this effect was 10(-14) M and was particularly pronounced with a concentration of 10(-8) M. The response reached maximum between the 3rd and the 5th min after application, persisted for 15-20 min, and was followed by a slight time-dependent decrease. Bombesin increased FES-produced relaxation of LES by 39% as compared to the control. The potentiating effect of bombesin on the LES relaxation was also observed after cholinergic and adrenergic receptor blockade. It is concluded that bombesin may modulate the release of cholinergic, adrenergic and noncholinergic, nonadrenergic inhibitory neurotransmitters. PMID- 2217909 TI - Purification of bovine cholecystokinin-58 and sequencing of its N-terminus. AB - Molecular cloning of cholecystokinin (CCK) mRNA from porcine brain and gut has demonstrated that CCK is synthesized as an identical precursor in both tissues. The sequence for porcine CCK-58 predicted from CCK cDNA was identical with the amino acid sequence of the peptide purified from different lots of animals. However one group did report that there were differences in the N-terminus of CCK 58 purified from the intestines of two different lots of mongrel dogs. In the current report it is demonstrated that the amino acid sequences of CCK-58 purified separately from three bovine brains are identical through the first 19 N terminal amino acid residues. The peptides were sequenced for ten additional steps and were shown to be identical with the previously reported sequences for the N-terminus of CCK-39. The N-terminus of bovine CCK-58 has the following sequence: AVPRVDDEPRAQLGALLAR. PMID- 2217910 TI - Peptide biology: the value of non-mammalian models. Bayliss & Starling 10th annual meeting. Egham, 2-3 September 1990. Abstracts. PMID- 2217911 TI - [New portable spectrometry recording system]. AB - The variations of environmental gamma radiation flux were observed by using a new portable spectrometry recording system for 1 year. Spectrum analyses by the response matrix method have provided much information, and the artificial contribution can be separated from natural back ground dose by using the Th method or the three component method. PMID- 2217912 TI - [Chemical constituents of some biodegradable liquid scintillators]. AB - Chemical constituents of the commercially available "biodegradable" liquid scintillator solvents were elucidated by means of GC/MS analysis etc., as either the mixture of monosubstituted benzenes with the alkyl chain of carbon 10 to 13, or 1-(3,4-dimethylphenyl)-1-phenyl-ethane. PMID- 2217913 TI - [Food irradiation: global aspects and future prospects]. PMID- 2217914 TI - [Measurement of radiation energy and its application. IV. Measurement of beta-ray energy and its application (6). Liquid scintillation spectrometry]. PMID- 2217915 TI - Quantitative factors in chemical carcinogenesis: variation in carcinogenic potency. AB - The quantitative assessment of toxicological data on the carcinogenic potential of chemicals requires consideration of a number of factors, including mathematical models of the mechanism of carcinogenic action and pharmacokinetic models for the metabolic activation of the parent compound to its reactive metabolite. In this article, the use of such models in estimating carcinogenic potency and in predicting risks at low levels of exposure is discussed, along with other factors involved in the evaluation of carcinogen bioassay data. The Carcinogenic Potency Database (CPDB) established by Gold et al. (1984, Environ. Health Perspect. 58, 9-322) is used to illustrate the application of quantitative approaches to carcinogenic risk assessment and to examine the variation in the potency of chemical carcinogens. Based on an analysis of 585 experiments selected from the CPDB, the risk-specific (10(-6) doses (RSDs) obtained by linear extrapolation from the TD50 were generally within a factor of 5-10 of those derived from the linearized multistage model. The RSDs obtained by linear extrapolation from the TD50 are roughly log-normally distributed with a median of about 20-90 ng/kg/day, depending on the subset of the CPDB considered. This distribution has been used by Rulis (1986, in Food Protection Technology (C. W. Felix, Ed.), pp. 29-37, Lewis, Chelsea, MI) to explore the concept of a threshold of regulation for chemical carcinogens present in the environment at low levels. PMID- 2217916 TI - Safety assessment procedures for indirect food additives: an overview. Report of a workshop. PMID- 2217917 TI - Screening procedures for evaluating the potential carcinogenicity of food packaging chemicals. PMID- 2217918 TI - Mechanistic considerations in chemical carcinogenesis. PMID- 2217919 TI - Consumer perception of cigarette yields: is the message relevant? AB - Over 1200 randomly selected subjects from the U.S. and key European countries were interviewed by telephone, to establish how consumers perceive the meaning and relative value scale of tar yields of commercial cigarettes. Some 50% of respondents interpreted numerical tar yields as being precise quantitative predictors of intake related to health effects. A less precise quantitative intuition is shown by 20-30% of respondents. The remaining respondents had little or no interest in, or understanding of, tar yield meaning. Despite local differences, the aggregate responses from the U.S. were analogous to European responses and were not significantly affected by age, sex, or socioeconomic status. The results show that consumers expect a cigarette grading message predictive of actual intake from different brands. The current message based on standard analytical yields does not meet this requirement and needs modification. Cigarette ratings based on the tar-to-nicotine ratio of standard yields could offer the basis for an acceptable message. PMID- 2217921 TI - Preliminary adult soil ingestion estimates: results of a pilot study. AB - Six adults were evaluated for the extent to which they ingest soil. This study was originally part of a large childhood soil ingestion study and was used to validate part of the analytical methodology used in that larger study. The adult study followed the soil tracer methodology of the children's study. The principal findings of the adult study revealed that the four most reliable tracer elements based on recovery studies in a mass balance assessment [aluminum (Al), silicon (Si), yttrium (Y), and zirconium (Zr)] yielded the following mean daily adult soil ingestion estimations: Al (77 mg), Si (5 mg), Y (53 mg), and Zr (22 mg). The median daily soil ingestion estimations based on these same tracer elements were: Al (57 mg), Si (1 mg), Y (65 mg), and Zr (-4 mg). These findings represent the first published quantitative estimates of soil ingestion by adults. PMID- 2217922 TI - Biotechnologies and food: a summary of major issues regarding safety assurance. PMID- 2217920 TI - Acute toxicity testing in the nonlethal dose range: a new approach. AB - A new modification of acute toxicity testing of chemicals in rats is presented. Instead of using death as the principal criterion of toxicity, it is based on a careful, standardized clinical assessment of toxic signs measured in the nonlethal dose range. Test compounds are administered to groups of rats at four dose levels, selected on the basis of pilot experiments. General indices of toxicity, i.e., body weight gain, food and water consumption, and body temperature, are recorded at regular intervals; activity in the home cage is monitored continuously with a newly developed passive infrared device; neurobehavioral dysfunctions are assessed repeatedly with a checklist; and routine hematology is done on the 4th day after administration of the test compounds. All measured signs of toxicity are scored in relation to the control groups so that the absolute magnitude of the score increases as a function of the deviation from the normal conditions of the animals. In order to take into consideration the course of intoxication and the rate of recovery, toxicity scores are added over the duration of the whole experiment. For each variable measured, the resulting total scores are converted into a relative point system, scaling from 0 to 10 points. These points are added to a single "total ToxScore" value for each dose group. A regression line is calculated for these total ToxScore points, and the dose giving 15 total ToxScore points is determined. Based on the results obtained with nine reference substances, a classification system is proposed that is comparable to that based on LD50 values. It is concluded that the proposed test procedure provides much more information on the signs of acute toxicity, the course of the intoxication, the slope of the dose effect curve, and the rate of recovery than does the standard LD50 test. In addition, the degree of distress and suffering of the animals is reduced. PMID- 2217923 TI - [Radiologic study of osteopenic syndromes. Between tradition and innovation]. PMID- 2217924 TI - [Emphysematous cholecystitis. Description of a case]. PMID- 2217925 TI - [Peripyelic and peri-ureteral non-Hodgkin's lymphoma]. PMID- 2217927 TI - [Magnetic resonance of the heart: imaging and spectroscopy]. PMID- 2217926 TI - [A case of death following the intravenous administration of an organo-iodinated contrast media of low osmolality]. PMID- 2217928 TI - NMR assessment of valvular disease. PMID- 2217930 TI - [Magnetic resonance in hypertrophic cardiomyopathy]. PMID- 2217929 TI - [Magnetic resonance in dilated, restrictive and arrhythmogenic cardiomyopathies]. PMID- 2217931 TI - [Magnetic resonance in the study of cardiac dysplasia]. PMID- 2217932 TI - [Computerized tomography and magnetic resonance in the study of the pericardium]. PMID- 2217933 TI - [Magnetic resonance of tumors of the heart]. PMID- 2217934 TI - [Fundamental aspects of magnetic resonance spectroscopy in vivo]. PMID- 2217935 TI - Magnetic resonance spectroscopy of the heart. PMID- 2217936 TI - Localized 31P-spectroscopy of the human heart. PMID- 2217937 TI - MR imaging and MR spectroscopy of the heart: present and future possibilities and limitations. PMID- 2217938 TI - [Modular project of the Picture Archiving and Communication System (PACS). Preliminary clinical experience. II]. AB - In the previous paper in this volume the PAC System installed in the Radiology Department of the University of Trieste has been described and its advantages and limitations have been analyzed, mainly from an operational point of view. This paper deals with the clinical evaluation of the system in ordinary operative conditions. A series of cases with specific characteristics was monitored in order to reveal different performances in both diagnostic process and conclusions using the PACS viewing console (DW) vs. conventional CRT film images on alternators. In a first test, 100 routine (not pre-selected) brain CT cases were independently analyzed by 4 radiologists, each of them giving 2 interpretations of the same case, one based on film and the other on PACS. The data were analyzed by conventional statistical methods, showing a substantial agreement of the results obtained with the 2 modalities. A second test concerned the evaluation of 100 lumbar intervertebral disks by CT, with the same procedure as above. Four radiologists were again asked to decide on film and PACS images about normality, protusion, or herniation of the disks. The results demonstrate the possibility of adequately reporting on the PACS monitor and stress the need of an adequate training period and the efficacy of the image processing capabilities of the system. PMID- 2217939 TI - [Radiologic picture of the thorax in acute asphyxia caused by near drowning. A caseload contribution]. AB - One hundred-fifteen drowning and near-drowning patients were hospitalized in Jesolo and Mestre over the last 10 years. A correlation between radiological patterns and clinical features was thoroughly investigated by the authors. A close relationship was found between clinical findings and the X-ray pattern of the first radiography, taken immediately after the rescue. The longer the hospitalization (or when SNC is assessed) the less significant the correlation. According to the author's experience, prognosis is good when the first radiograph does not demonstrate any lesions. On the contrary, when lesions are seen on the first radiograph the patient is to be carefully monitored in order to treat every complication promptly, including ARDS (10% of all cases). Chest radiographs are also useful to explain autopsy findings. No typical radiological pattern was found: however, four signs were observed, which were very frequently associated i.e., bilateral parenchymal shadows, pneumothorax, pneumopericardium, and gastrectasia. These findings appear to be characteristic of near-drowning. PMID- 2217941 TI - [Magnetic resonance in the evaluation of mediastinal masses]. AB - Thirty-three patients with mediastinal masses were examined by means of MRI to obtain elements for lesion characterization, to evaluate lesion extent, and to assess the relationship of the mass to the surrounding structures, especially the great vessels (accuracy: 84.84%), mediastinal structures (accuracy: 76.78%), and lung parenchyma (accuracy 69.69%). MR data were compared to CT findings; sensitivity, specificity and accuracy were subsequently compared to surgical and histologic findings. The results have shown MRI to be a very reliable method in the evaluation of mediastinal masses. PMID- 2217940 TI - [Diagnostic reflections on lung lymphangioleiomyomatosis]. AB - Two cases of histologically proven pulmonary lymphangiomyomatosis were studied by means of an adequate combination of the current imaging modalities. After an anatomical survey of the secondary pulmonary lobule, the authors discuss the pathologic appearance, the pathogenetic factors (mainly hormones), and the diagnostic problems concerning this pathologic condition. Finally, the authors emphasize the decisive role of high-resolution CT (HRCT) in the evaluation of pulmonary lymphangioleiomyomatosis. PMID- 2217942 TI - [First experience with the combination of ultrasonics and pulsed Doppler (Duplex system) in the study of venous pathologies of the legs]. AB - Over a 2-year period the authors examined 400 patients affected with different types of phlebopathies with combined real-time US and pulsed Doppler (Duplex system). Ninety-eight patients had deep phlebothrombosis, 45 had superficial phlebothrombosis, and 110 primitive or secondary vein insufficiency. The obtained data, supported in 171 cases by contrastographic findings, allowed both the semeiological study and the evaluation of the indications for Duplex US in the various phlebopathies. The combination of high-resolution US morphological data, dynamic tests, and the functional data from pulsed Doppler have particular interest in the study of: a) the diagnostics of superficial or deep thrombosis and adhesive or floating thrombi; b) post-thrombotic syndrome; c) primitive or secondary vein insufficiency; d) the ostium of the superficial venous system (location, morphology, functionality). Duplex US is a non-invasive technique for the examination of the superficial and the deep venous systems, which reduces the indications for phlebography, an exam which requires radiation exposure, and is not always safe or possible. Duplex US is however limited by the difficult assessment of the venous system below the knee, because of too many trunks and variants. PMID- 2217943 TI - [Injury of the large vessels of the neck caused by radiation of neoplasms of the otorhinolaryngologic region: a study using Doppler echography]. AB - Twelve patients undergoing radiotherapy for pharyngo-laryngeal neoplasms were compared to a control group by means of duplex-Doppler US in order to evaluate early and late radiation-induced damage to the main arterial vessels in the neck region. On first examination the case distribution regarding the presence/absence of preexisting vascular lesions was: no lesions (8.3%), mild (33.3%), moderate (16.6%), and severe (41.6%) atherosclerotic lesions. The subjects included in the control group presented with similar characteristics, so that they had similar features to the patients undergoing radiotherapy. While no early complications were demonstrated, development and/or progression of parietal lesions were detected 1 year after the first examination in 58% of patients. No variations were observed in the control group. Radiation-induced damage to the arterial wall was subdivided into 2 groups: moderate (42%) and severe (16%). Damage to neck vessels, though allowing for the small number of patients and the short follow up, has to be referred to radiotherapy, since no changes were detected in the control group. In the authors' opinion, follow-up by means of hematochemical exams and duplex-Doppler US of the neck is advisable to evaluate general risk factors and to select those patients who can fruitfully undergo surgical treatment. PMID- 2217944 TI - [Intra-arterial digital angiography using a trans-humeral approach in the assessment of ambulatory patients]. AB - The authors report their experience with intraarterial digital subtraction angiography (DSA) performed on outpatients via brachial artery catheterization. A total of 120 outpatients were studied for cerebral and lower limbs vascular diseases. Transbrachial catheterization was performed with 5F or, preferably, with 4F angiographic catheters. Success rate was high and the transbrachial approach was always easy. In the course of cerebral examination (18/120 cases) the catheter was always easily positioned in the ascending thoracic aorta, through right transbrachial approach. In the course of abdominal aorta and lower extremities examination (102/120 cases), the ideal catheter positioning--in the descending aorta--was performed in 95/102 cases, by left transbrachial approach, while in 7/102 patients the catheter was placed in the ascending aorta. The complication rate was low: 7/120 ecchymosis, 4/120 small hematomas spontaneously resorbed, and 2/120 transient spasms of brachial artery. The authors suggest trasbrachial intraarterial DSA as an alternative to intravenous DSA in outpatients. PMID- 2217945 TI - [The enhancement phenomenon of serous cavity effusions]. AB - The enhancement of ascites following a high dose of contrast medium has been recently described. The CT behavior of 26 peritoneal, pleural or pericardial effusions has been studied in 23 patients after the administration of a high dose of urographic contrast medium. The effusions were enhanced in all patients but one. No difference between malignant and non-malignant effusions could be observed with ionic and non-ionic contrast medium. Low molecular weight of the urographic contrast medium (600-800 daltons) can explain the free passage of the solute through peritoneum, pleura, and pericardium. The knowledge of such a phenomenon is mandatory to avoid misdiagnosing hematic effusion or urinary peritoneal fistula. PMID- 2217946 TI - [Creation and management of a data bank in oncologic radiotherapy]. AB - Clinical, scientific and technological development has greatly widened the scope and range of oncological radiotherapy. As for database management, favorable conditions come from new available hardware and software facilities and from well consolidated and universally accepted classifications. The authors' aim was to create and to verify an original database management system for oncological radiotherapy, proved with internationally accepted classifications and directly interfaced to a new package for clinical and epidemiological statistics. An ordinary personal computer was used and a 802-subject statistics was analyzed relative to 1987-1988 series from the Istituto del Radio "O. Alberti", General Hospital and University - Radiotherapy Department, Brescia, Italy. The system seems to be suitable for routine use as well as for research, with good potentials for multicentric use. PMID- 2217947 TI - [Preoperative localization using a bidimensional mammographic technique of non palpable lesions of the breast]. AB - It is widely known how the early diagnosis and treatment of breast cancer may lead to better prognosis. When a non-palpable breast lesion detected with mammography is correctly localized with fine-needle biopsy under X-ray guidance, the surgeon can easily remove the lesion while preserving normal breast tissue. In such cases, histology is also possible. The authors describe an easy bidimensional technique for the preoperative localization of occult nonpalpable breast lesions with a fine-needle. The procedure is feasible also with out-of date equipment and does not cause any discomfort to the patients. It should be performed on all women with mammographic suspicion of non-palpable breast lesion. From January through December 1989 the authors performed 64 preoperative fine needle biopsies of clinically-occult breast lesions. The presence of a lesion associated with microcalcifications was found to be indicative of malignancy more often than in the case of microcalcifications or lesions alone. Of 64 cases, histology demonstrated malignancy in 31 patients. PMID- 2217948 TI - [Modular project of the Picture Archiving and Communication System (PACS). Preliminary operational experience. I]. AB - Since september 1988 a PAC System (Comm View by AT & T and Philips) has been operating in the Radiology Department of the University Hospital, Trieste. A research project is presently in progress aiming at providing factual evidence for the evaluation of this kind of systems as far as operational, technical, clinical and economic aspects are concerned. The general approach to this research consists in implementing and monitoring a PACS in a stepwise way, starting with a small system connected to some digital modalities only, in order to test the feasibility and effectiveness of the system within a Radiology Department, and to test the possibility of matching the PACS to the Radiological System. The present paper describes in detail the present configuration of this entry-level system and its technical features. The planned development (october 1989) is also depicted. Further developments devise at managing in an integrated way all the radiological images of the four hospitals of Trieste. At present, the PACS is currently used to manage and store on optical disks all the images acquired from the connected modalities plus the related reports, and to perform the reporting sessions for CT examinations (brain and abdomen). The present research effort is devoted to two main areas: clinical evaluation and operational analysis. The object of the operational analysis was the assessment of the impact of PACS on the operations of a Radiology Department. The general approach followed for this research consists in analysing the procedures as they are performed in the conventional way (manual operations), and comparing them to the way they are, or could be, performed using a PACS System (automatic operations). This stage of the project is divided into three phases, concerning respectively the analysis of the organization and operations before PACS, the analysis of the impact of PACS in its initial configuration and the forecast of the influence of PACS in its future setting. A first evaluation concerned the activities carried out from the moment the images are generated to the moment they are ready to be achieved. They include image acquisition, reporting, delivering and returning of images from the departments. The time required to carry out each of the activities involved was recorded, both in the manual and in the automatic version; furthermore, a more detailed analysis was performed on the reporting procedure. The conclusions reached through this analysis are that this kind of operation is mostly affected by the way the Radiology Department is managed, rather than by the tools employed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2217949 TI - [Chiasmal hernia in secondary empty sella. Magnetic resonance images in an asymptomatic patient]. PMID- 2217950 TI - [Pneumopathy caused by amiodarone. Description of a case]. PMID- 2217951 TI - [A case of giant fibrolipoma of the esophagus. Diagnosis using computerized tomography and double-contrast esophagography]. PMID- 2217952 TI - [Maternal and neonatal plasma concentrations of bupivacaine during peridural anesthesia for cesarean section]. AB - Many anesthesiologists prefer epidural anesthesia for cesarean section because of the potential risks of general anesthesia such as Mendelson's syndrome. For this indication, the local anesthetic of first choice is the long-acting substance bupivacaine. The aim of the following study was to determine maternal and neonatal plasma concentrations of bupivacaine 0.5% following epidural anesthesia for cesarean section in order to give critical statements about the systemic toxicity of the local anesthetic. MATERIALS and METHODS. Central venous blood samples were collected for bupivacaine analysis (gas chromatography) in 15 patients (Table 1) undergoing cesarean section with epidural anesthesia over a period of 60 min after injection of 14 to 23 ml bupivacaine 0.5%. Six of these patients had received the epidural anesthesia earlier to relieve labor pain. Before administering the anesthetic dose, a blood sample was taken to determine the baseline value. Immediately after cord clamping, blood sampling was done to determine bupivacaine concentrations in the umbilical artery and vein. Apgar scores and blood gases were also checked and compared with those of neonates born by cesarean section under general anesthesia. RESULTS. Ten to 15 min following epidural application of 70 to 115 mg bupivacaine (mean = 99 mg), peak plasma concentrations occurred (mean = 0.41 micrograms/ml) The maximum plasma level of 0.7 micrograms/ml bupivacaine was found in a patient who had received epidural anesthesia for pain relief during labor. In this case, the baseline bupivacaine level after several epidural injections (125 mg in 15 h) before the anesthetic dose for cesarean section was 0.2 micrograms/ml. Immediately after delivery the mean plasma bupivacaine concentrations in the umbilical vein and artery were 0.11 micrograms/ml and 0.07 micrograms/ml respectively. Apgar scores and blood gas analyses showed no significant difference between neonates born by cesarean section under regional or general anesthesia. DISCUSSION. Using bupivacaine 0.5% for epidural anesthesia for cesarean section, we found maternal and neonatal plasma concentrations of the local anesthetic far below the accepted threshold level for producing systemic toxic reactions. In contrast to others, we obtained good analgesia and sufficient motor blockade accompanied by low plasma levels. In our opinion, there is no need to use 0.75% bupivacaine, especially since peak plasma concentrations of more than 2 micrograms/ml occur shortly after its epidural administration. PMID- 2217953 TI - [Transient medium- and deep-tone hearing disorders following spinal anesthesia]. AB - In a prospective study, 100 patients who underwent general surgical or urological operations under spinal anesthesia were examined to determine whether there was a relation between the anesthesia and postoperative hearing loss. Audiograms were performed preoperatively and as the 1st, 2nd, 3rd, and 5th postoperative days. It was found that 16 patients had impairment of hearing. The average ages of these patients were similar to those of the total population. The hearing loss was typical: only the frequencies between 125 and 2000 Hz were affected. It began on the 2nd day after spinal anesthesia and disappeared within 3 days without special therapy. The cause of this typical hearing loss after spinal anesthesia is a drop in cerebrospinal fluid pressure transmitted to the perilymph via the cochlear aqueduct. The change in the endoperilymphatic pressure difference results in a change in the oscillation of the basilar membrane. Because 16% of patients may suffer hearing loss after spinal anesthesia, it seems reasonable from a medicolegal point of view to explain the possibility of defective hearing to the patient. PMID- 2217954 TI - Osteoarthritis. AB - In summary, the relationship between risk factors and OA may differ across joints. For knees, obesity and knee injury either due to acute events or to repetitive impact loading may be the most important preventable causes of disease. Hand OA is probably also caused by repetitive use, but its association with other risk factors is unknown. Hip OA is probably different from OA in other joints, in that many cases are due to congenital and developmental abnormalities. Current inquiry focuses on generalized OA and its predictors. Future studies will look at the long-term course of OA and will focus especially on as-yet unidentified risk factors. PMID- 2217955 TI - Epidemiology of rheumatic disease. PMID- 2217956 TI - Rheumatoid arthritis. AB - RA is a common disease with a worldwide prevalence of about 1% with an annual incidence of about 3/10,000 adults. It is two to three times more common in women. There is some evidence that over the last few decades the disease is declining in incidence or severity. Patients with RA have a reduced life expectancy and a one in three chance of becoming disabled, depending on the severity of the disease at onset. The cause of the disease is unknown, although genetic factors account for up to 30% of disease susceptibility. The most important genetic factors are related to HLA-DR4 and DR1, which may have identical regions conferring the risk of disease. Many infectious agents have also been implicated in the etiology of RA, although there is no good epidemiologic evidence to support the laboratory findings. Hormonal and reproductive factors are known to play a major role in disease pathogenesis. Both pregnancy and the oral contraceptive pill are believed to be protective against development of the disease, although they may act by delaying or modifying the course of the disease rather than conferring "immunity". PMID- 2217957 TI - Gout and hyperuricemia. AB - The prevalence of gout in the United States has been rising steadily for the past two decades. Hyperuricemia is considered a necessary but not sufficient precondition for gout. Known risk factors for gout include male sex, hypertension, renal insufficiency, obesity/weight gain, diuretic use, lead exposure, and family history. The association of gout and hyperuricemia with coronary artery disease is controversial. Current evidence from the Framingham Study suggests that gout is in fact an independent risk factor for CHD. These data suggest that patients with gout should be screened for modifiable risk factors for CHD, and that early intervention in such patients may be worthwhile. Finally, the effect of AHU as risk factor for CHD remains unclear but is probably a weak one. PMID- 2217958 TI - Ankylosing spondylitis and other spondyloarthropathies. AB - Ankylosing spondylitis and related spondyloarthropathies show a remarkable association with a genetic marker--HLA-B27--and also illustrate the relationship between host and environmental factors. HLA-B27 has revitalized the epidemiology of spondyloarthropathies and has helped to broaden the clinical spectrum of these diseases. These and other aspects of descriptive and genetic epidemiology are reviewed. PMID- 2217959 TI - Rheumatic diseases of childhood. AB - Development of diagnostic criteria for juvenile rheumatoid arthritis, systemic lupus erythematosus, a juvenile dermatomyositis, as well as advances in molecular biology, have assisted epidemiologic study of the rheumatic disorders of childhood. It may be misleading to extrapolate the incidence and prevalence of pediatric forms of arthritis from population studies of adults. Additional study of the frequency of childhood musculoskeletal disorders is very much needed. Classification criteria for Kawasaki syndrome, fibrositis in children, and the juvenile spondyloarthropathies are also desirable. PMID- 2217960 TI - Lyme disease. PMID- 2217962 TI - Systemic sclerosis. AB - Systemic sclerosis is a disease characterized by several distinctive features. This disease spares children, and its incidence increases steadily with age. Women are affected more than men, especially during childbearing years. Although there is no overall racial predilection, SSc occurs most frequently and severely in young black women. Family and genetic studies suggest only a weak genetic predisposition, but there are many occupational agents that may be implicated in the pathogenesis. The disease with its involvement in many organ systems results in a significant reduction in lifespan. Improvement in survival of renal crisis has been dramatic with the use of ACE inhibitors. Further epidemiologic studies using subsets of patients with more homogeneous clinical and laboratory features will lead to a better understanding of this complex disease. PMID- 2217961 TI - Systemic lupus erythematosus. AB - Descriptive epidemiologic studies of SLE have been conducted worldwide; the most extensive data are available for Scandinavia, especially Sweden, and the United States. In the United States, blacks have threefold higher incidence, prevalence, and mortality rates compared with whites; the reasons for this excess, however, remain unknown. Analytic and genetic epidemiologic studies suggest a multifactorial etiology of SLE; results support a polygenic mode of inheritance including important roles for an autosomal dominant "autoimmune" gene and female sex hormones. Although a viral etiology remains attractive, there is little evidence to support such a hypothesis. Rather, other environmental factors including chemical exposures may be important as "triggers" of disease. Finally, observational epidemiologic studies demonstrate an increasingly favorable prognosis for patients with SLE, allowing a better understanding of long-term morbidity and impact on overall health status. Future epidemiologic studies should focus on identifying noninfectious environmental etiologic factors and improving the quality of life for all patients with SLE. PMID- 2217963 TI - Idiopathic inflammatory myopathies. AB - The idiopathic inflammatory myopathies are a heterogeneous group of uncommon diseases. The incidence rate of IIM is approximately 5 cases per million population, but there appears to be an increase in the rate over the last two decades, particularly in black females. This may be a true increase or due to renewed interest and awareness of the disease and improvement in our ability to diagnose mild disease. There has also been progress in decreasing the mortality rate in IIM perhaps secondary to better treatment and/or the diagnosis of mild disease. The discovery of anti-Jo-1 antibodies has renewed the investigation of a possible viral etiology of IIM. Studies of quantitative slot blot hybridization with coxsackievirus probes and RNA from IIM muscle biopsies and in situ hybridization of biopsies with a Theiler's virus probe have revealed a few positive hybridizations in each study. Although there are some fundamental problems with these studies, these intriguing results bear confirmation. These results continue to implicate picornaviruses as the primary suspects in the pathogenesis of IIM. HIV has now been associated with a number of rheumatologic syndromes, including a polymyositis that is indistinguishable from IIM, and we can expect additional changes in the epidemiology of this family of disorders in coming years. Study of these patients may provide insight into the etiopathogenesis of IIM. PMID- 2217964 TI - Polymyalgia rheumatica/giant cell arteritis and other vasculitides. AB - The epidemiology of vasculitic syndromes encompasses a broad spectrum of diverse clinical syndromes. Almost all lack identified etiologic agents, and their clinical characteristics are determined predominantly by the size of the involved vessel and the end organs damaged. With the exception of giant cell arteritis/polymyalgia rheumatica in the elderly, and Henoch-Schonlein purpura and Kawasaki disease in the pediatric population, the vasculitic syndromes are infrequently observed diseases. PMID- 2217965 TI - Fibromyalgia. AB - There has been confusion surrounding regional medical conditions, primary psychological conditions, and fibromyalgia in practice and in the literature. Confusing terminology and inappropriate use of diagnostic criteria have contributed to this problem. Use of the 1990 ACR Criteria for the Classification of Fibromyalgia together with the symptom and physical examination definitions in that report should go far to correct these problems. Problems of selection and identification bias filter patients with the syndrome, and almost all reports concerning the disorder have been obtained from subspecialty clinics. Almost nothing is known about fibromyalgia in the community, and characteristics of patients noted in the clinic may be a primary function of these biases. In general, in the clinic, about 90% of patients are women of a mean age slightly less than 50 years. Onset is noted in childhood and in old age, but most commonly in middle life. Trauma, surgery, and infection have been noted in association with development of the syndrome in some reports. More than 10% of patients attending general medical clinics and 15-20% attending rheumatology clinics have the syndrome. Chronicity is the rule. Work disability occurs, but most patients seem to be able to work, although some have changed jobs to accomplish this. Psychologic abnormalities are noted in most, but not all, reports, but may reflect selection bias and could be absent in the community. PMID- 2217966 TI - Osteoporosis and hip fractures. AB - Epidemiologic studies have contributed to our understanding of osteoporosis through identification of groups at high risk of fracture and through discernment of factors associated with increased risk of low bone density and fracture. Many of the questions remaining can be addressed only through the use of epidemiologic methods in human populations. These include longitudinal studies in large cohorts to better delineate factors associated with bone loss and fracture and randomized clinical trials to adequately assess therapies. Particularly needed are studies in adolescents to assess determinants of peak bone mass and the effect of subsequent bone loss with aging. PMID- 2217967 TI - Design and conduct of collaborative international epidemiologic studies of rheumatic diseases. AB - Collaborative international epidemiologic studies are important endeavors for improving our understanding of health and disease. They can help answer questions relating to genetic and environmental factors that may plan a role in the etiology and pathogenesis of the disease under study. These studies are challenging but can be very rewarding. There are many opportunities for collaborative international epidemiologic studies in rheumatology which can be explored. PMID- 2217968 TI - Rheumatic diseases in the U.S.S.R. AB - Despite our inability to precisely prognosticate disease, accumulation of knowledge about risk factors allows us to form a real basis for attempts at primary prevention of rheumatic disease. Because rheumatic diseases are multifactorial in nature, it may be suggested that the more factors an individual has the higher is the risk of disease. Relative risk values are certain to have a known limitation, since they are not independent. In addition, the number of risk factors may be significantly more than that known today. Increasing our knowledge in disease etiology and pathogenesis will definitely increase the number of risk factors. At the same time, available data may serve as a basis for developing a system for individual and group prognosis, the latter being to a certain degree tentative for the majority of diseases. All factors affecting disease development and course are divided into the controllable and the uncontrollable. The majority of the factors mentioned--especially, the environmental--are controllable ones. So the challenge facing practitioners and scientists involves development of a comprehensive system of recommendations aimed at elimination or maximum lessening of unfavorable risk factors, which is the only real basis for primary rheumatic disease prophylaxis. PMID- 2217969 TI - RadioGraphics update: announcements and new features. PMID- 2217970 TI - Techniques for color flow sonography of the lower extremity. AB - Color flow sonography permits noninvasive examination of the deep venous system in the lower extremity. In many patients, the modality is sufficiently accurate to serve as the sole diagnostic procedure for suspected deep venous thrombosis. Over 1,500 color flow sonographic examinations of the lower extremity have been performed at our institutions with various scanning techniques. For the inexperienced sonographer, we describe our current technique, which is easy, quick, accurate, and well tolerated by patients. PMID- 2217971 TI - Ethanol embolization of vascular malformations. AB - Absolute ethanol was used to treat 20 patients with symptomatic vascular malformations (SVMs) (ie, venous malformations, arteriovenous malformations, and congenital and posttraumatic arteriovenous fistulas) in whom previous surgery or standard embolotherapy had failed or who were not candidates for surgery. All large complex lesions required multiple embolizations as staged procedures. Immediate thrombosis was achieved in all patients; complications (13% of cases) were generally minor and were treated conservatively. Follow-up studies, performed in 19 of 20 patients, showed persistent occlusion of the SVM in all cases. Ethanol embolization of SVMs, performed according to strict techniques, has proved efficacious in SVM management and is emerging as a definitive form of therapy. PMID- 2217972 TI - CT and MR imaging of the central skull base. Part 2. Pathologic spectrum. AB - The radiologist must have a thorough knowledge of the normal anatomy and the pathologic spectrum of the skull base to determine the extent of abnormality and to help plan the surgical approach. The authors describe and present examples of congenital, benign, and malignant lesions that affect this region, including cephalocele, fracture, fistula, juvenile angiofibroma, meningioma, chordoma, pituitary adenoma, chondrosarcoma, nasopharyngeal carcinoma, and rhabdomyosarcoma. Metastatic, infectious, and other miscellaneous processes are also discussed. Imaging strategies with computed tomography and magnetic resonance imaging to aid in the diagnosis are suggested. PMID- 2217973 TI - Otic capsule dysplasia: clinical and CT findings. AB - Many congenital dysplasias of the osseous labyrinth have been identified. Differentiation of these dysplasias is essential for patient management. High resolution computed tomography (CT) was used to identify individual malformations in 32 patients. Thirty patients had six previously described forms, while two patients had a form that has not previously been reported to our knowledge. Review of patient histories revealed clinical characteristics that were specific for certain forms of otic capsule dysplasia. CT enabled detailed analysis of each lesion and helped direct proper treatment of each patient. The characteristic CT appearance and clinical presentation of each form of dysplasia are presented. PMID- 2217974 TI - CT of thoracic aortic aneurysms. AB - Aneurysms of the thoracic aorta are most often the result of arteriosclerotic disease. Other causes include degeneration of the medial layer of the aortic wall, either idiopathically or due to genetic disorders such as Marfan syndrome; aortic dissection; trauma; syphilis and other bacterial infection; noninfective aortitis; and congenital anomaly. We review normal anatomy of the aorta and discuss our technique and interpretation of computed tomography (CT) in the evaluation of the thoracic aorta. We illustrate the CT appearance of different types of aortic aneurysms as well as discuss the use of CT for assessing complications of aneurysms, for postoperative follow-up, and in the differentiation of aortic aneurysm from a paraaortic mass. PMID- 2217975 TI - Internal mammary lymphadenopathy: imaging of a vital lymphatic pathway in breast cancer. AB - The prognostic significance of metastases to the internal mammary lymph nodes in patients with breast carcinoma has long been recognized. While ipsilateral dissection of axillary nodes remains a popular staging strategy for breast cancer, surgical sampling of the upper anterior intercostal spaces, a tedious procedure, has been largely abandoned. Diagnostic imaging of the parasternal lymphatic pathway is a useful and noninvasive alternative to surgical staging. This report reviews the pertinent regional anatomy and illustrates the criteria for diagnosing internal mammary lymphadenopathy by means of lateral chest radiography, computed tomography, high-resolution sonography, magnetic resonance imaging, and radionuclide lymphoscintigraphy. PMID- 2217976 TI - Nonosseous accumulation of bone-seeking radiopharmaceuticals. AB - Bone scintigrams are usually obtained for evaluation of skeletal abnormalities; soft-tissue abnormalities are often an unexpected finding. However, the recognition of specific conditions with extraskeletal accumulation of bone seeking radiopharmaceuticals greatly enhances the diagnostic value of the study. Several examples of abnormal nonosseous uptake in both neoplastic and nonneoplastic processes involving the brain, lung, heart, breast, bowel, liver, spleen, skeletal muscle, kidney, and bladder are presented. Examples of artifactual uptake in the soft tissues are also described. Causes for nonosseous accumulation are discussed. PMID- 2217977 TI - Image interpretation session. PMID- 2217978 TI - Primary Ewing sarcoma of rib. AB - Ewing sarcoma is a relatively common, highly malignant bone tumor that typically occurs in adolescents and young adults aged 10-25 years. Our archives contain 328 cases of histologically proved and radiologically correlated Ewing sarcoma collected in consultation over 40 years. From this series, we identified 34 lesions (10%) arising in ribs. Radiographically, the affected rib was predominantly lytic in most (82%) cases, but mixed lytic-sclerotic (9%) and even predominantly sclerotic (9%) patterns were also encountered. The affected rib was "expanded" in 35% of cases, although the contour change was usually mild. Abnormalities of the affected ipsilateral hemithorax varied from subtle, isolated rib involvement to solitary rib involvement accompanied by complete opacification of the hemithorax. We describe the spectrum of radiologic findings of primary Ewing sarcoma of rib, augmented where appropriate by accompanying pathologic material. PMID- 2217979 TI - Introduction to the history of musculoskeletal radiology. PMID- 2217980 TI - Cases of the day. Pediatric. Myositis ossificans circumscripta. PMID- 2217981 TI - Cases of the day. Pediatric. Amniotic band syndrome. PMID- 2217982 TI - Cases of the day. Ultrasound. Focal nodular hyperplasia of the liver. PMID- 2217983 TI - Cases of the day. General. Benign thymic cyst complicated by hemorrhage. PMID- 2217984 TI - [Osseous biocompatibility of Endomethasone(R)]. AB - The root canal filling paste "Endomethasone" was tested, following the F.D.I. criterions by bone implants on rabbits. The tissue reaction after four weeks can be appreciated as moderate and as mild after twelve weeks. Taking in count the criterions selected and the experimental conditions of this study, the "Endomethasone" can be considered as a root canal cement with acceptable in vivo tolerance. PMID- 2217985 TI - [Study of the section of different brands of K files and broaches]. AB - The authors of this article observed the cross section of different brands of K file and reamer, in order to compare the reality to the square or triangular symbol. On an other hand, they defined the ideal cross section of the endodontic instrument according to the user's requirements, and studied the most approaching one. PMID- 2217986 TI - [In vitro evaluation of the antibacterial activity of endodontic drugs]. AB - The antibacterial activity of camphorated phenol, iodine-potassium iodide, aqueous 2% glutaraldehyde, Rockles 4, Cresophene and Terra-Cortril has been tested in vitro against 21 species of bacteria. After 2 minutes of contact between medication and bacteria, Rockles 4, Cresophene, IKI and camphorated phenol inhibited completely all the tested bacteria. Terra-Cortril and aqueous glutaraldehyde 2% even pures were ineffective against all the bacteria species. Only Cresophene remained effective against 4 bacteria species when diluated 100 times. PMID- 2217987 TI - [A more efficient lateral condensation]. AB - Advantages and inconvenients of the lateral condensation technique are reviewed in this paper. Different ways to gain more efficient lateral condensation are studied: plugger and gutta-percha points selection and adaptation, combination with thermomecanical technique or assistance by ultrasonic or thermal systems. The study of these various methods and combinations leads to the concept of an thermolateral-assisted condensation. PMID- 2217988 TI - [Fistula and localization of dental origin]. PMID- 2217989 TI - [Design and fabrication of a complete removable denture opposing a fixed denture. 2]. PMID- 2217990 TI - [New hydrophilic silicones in clinical/laboratory relations]. PMID- 2217991 TI - [Influence of die preparation quality on the precision of fixed prosthodontics]. PMID- 2217992 TI - ["Opal" effect of the natural tooth in ceramometal]. PMID- 2217993 TI - [Photopolymerization through ceramic]. PMID- 2217994 TI - [Yesterday's dentures. 1]. PMID- 2217995 TI - [Multiple impressions one model]. PMID- 2217996 TI - [Yesterday's dentures. 2]. PMID- 2217997 TI - [New upper school of dental prosthodontics]. PMID- 2217998 TI - [Technical problems with dentures on implants]. PMID- 2217999 TI - [Fabrication of a ceramo-metal bridge with a Sunrise interface]. PMID- 2218000 TI - The hitch-hikers guide to nasal airway patency. PMID- 2218001 TI - Advances in our understanding of the pathogenesis of fibrotic lung disease. PMID- 2218002 TI - Primary pulmonary hypertension: diagnosis, medical and surgical treatment. AB - Primary pulmonary hypertension continues to present both diagnostic and therapeutic challenges to the physician, reflecting the lack of understanding about the basic mechanism of the disease. The natural history of the condition has been described only recently, and this has allowed a reasonably accurate prognosis for the individual patient to be determined. New treatments have been found effective, including heart-lung transplantation, which can now offer improved survival. Long-term intravenous infusion of prostacyclin has a place in the treatment of severely affected patients awaiting heart-lung transplantation. However, the major impact of prostacyclin has been, perhaps, to concentrate research upon the role of the endothelial cell in the development of this disorder, in particular the potential role of an impairment of release of the recently described endothelium-derived relaxing factor in certain forms of pulmonary hypertension. We have attempted in this review to focus on the problems of diagnosis and treatment together with current developments in the understanding of primary pulmonary hypertension. PMID- 2218003 TI - Nocturnal oxygen desaturation in patients using long-term oxygen therapy for chronic airflow limitation. AB - Nocturnal oxygen desaturation in patients receiving long-term oxygen therapy is described despite adequate daytime oxygenation (PaO2 greater than 8 kPa). Domiciliary oximetry overnight was performed on ten patients receiving long-term oxygen treatment for chronic airflow limitation: six patients were well saturated throughout the night with a fall in SaO2 to below 90% for only 1% of the monitoring time; four showed significant desaturation with a fall in SaO2 to below 90% for periods of 15-47% of the monitoring time. PMID- 2218004 TI - Concentration of tobramycin given by aerosol in the fluid obtained by bronchoalveolar lavage. AB - Whereas previous studies have used only bronchial secretions and sputum, in the present study, bronchoalveolar (BAL) fluid was analysed for tobramycin levels after aerosolization of this antibiotic. In 20 adult patients with a variety of lung disorders, the concentration of tobramycin obtained in the first aliquot of the bronchoalveolar fluid varied from less than 0.1 to 9.2 micrograms ml-1 (mean 2 +/- 2.26 micrograms ml-1) with 18 samples above 0.4 micrograms ml-1. In most of the cases, the concentration of tobramycin achieved values of tobramycin in excess of the minimal inhibitory concentration for most of the microorganisms. Thus, sampling fluids by the bronchoalveolar technique offers a suitable method to study antibiotic levels at the site of broncho-pulmonary infection. These results may help explain why aerosol antibiotic treatment appears to be useful in selected patients, especially in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa. PMID- 2218005 TI - Forced expiratory flow and oscillometric impedance measurement in evaluating airway obstruction. AB - The application of forced oscillations has been introduced as a noninvasive method to measure the impedance of the respiratory system. Impedance can be partitioned into a real part or resistance and an imaginary part or reactance. The reactance depends on the elastic and inertial properties of the respiratory system. In the present study, resistance and reactance obtained in a frequency spectrum between 4 and 52 Hz were compared with maximal forced expiratory spirometry in 100 out-patients, aged 18-70 years. Resonant frequency and frequency dependence of resistance correlated significantly with selected parameters of the forced expiratory flow volume curve: correlation coefficient values ranged from 0.492 between frequency dependence and FVC and 0.668 between resonant frequency and FEV1. No correlation between average resistance and spirometric parameters reached a statistically significant level. No marked difference was observed between spirometric parameters depending on the early or effort-dependent portion and those parameters depending on the late or effort independent portion of the maximum forced expiration. It can be concluded that each measurement procedure reveals different but characteristic information about the mechanical behaviour and properties of the respiratory system. PMID- 2218007 TI - Risk factors for hydrocortisone myopathy in acute severe asthma. AB - In one hospital over a 15-month period, four out of nine patients ventilated for acute severe asthma developed acute hydrocortisone myopathy. All patients had received less than 1.0 g day-1 hydrocortisone. Affected patients had severe generalized weakness which recovered over 1-6 weeks. When myopathic and unaffected subjects were compared, there was no clearcut difference with respect to age, sex, types of drug used, serum potassium levels, duration of ventilation and muscle paralysis, total dose of vecuronium bromide, or mean daily doses of hydrocortisone. The main difference between the two groups was in the total doses of hydrocortisone. The myopathic patients all received greater than 5.0 g hydrocortisone (range 5.4-10.2 g) and the others less than 4.0 g (range 0.9-3.5 g). The possibility that neuromuscular blockade might predispose to the development of myopathy is discussed. Hydrocortisone myopathy can occur when less than 1.0 g day-1 is used, and even with as little as 5.4 g given over 6 days. PMID- 2218008 TI - How well do the general public read Heaf skin tests? AB - The ability of 550 consecutive patients attending a tuberculosis clinic to grade their own Heaf skin test reaction, using an illustrated card designed for such self-reporting, was assessed. Individuals were asked to grade their own Heaf skin reaction and at the same attendance the reaction was formally graded by a respiratory health visitor. There was overall excellent agreement with only 58 (10.5%) disparate gradings. We conclude that self-reporting of Heaf skin tests using an illustrated card is simple, usually accurate and may preclude an otherwise unnecessary early reattendance. This study also validates an often used system of self-reporting. PMID- 2218006 TI - Comparative assessment of enprofylline and theophylline for chronic obstructive airways disease in the elderly. AB - Enprofylline, a recently developed xanthine derivative, is a more potent bronchodilator than theophylline. This study compares the efficacy and safety of enprofylline with theophylline for chronic obstructive airways disease (COAD) in elderly subjects. The study was of a randomized double-blind parallel design and commenced with a 1-week reference period when oral bronchodilators were withdrawn. Patients were then treated with either enprofylline or theophylline 150 mg bd for 2 weeks (period 1) followed by 300 mg bd for a further 3 weeks (period 2). Patients recorded peak expiratory flow rate (PEFR) and adverse experiences, if any, in a diary, daily. Of 111 patients recruited for the study, 85 entered active treatment (theophylline, n = 44; enprofylline, n = 41). Mean age was 72 years and mean bronchodilator reversibility was 22%. Enprofylline increased mean morning PEFR by 11% (period 1) and 19% (period 2) whereas theophylline increased PEFR by 13% and 19%, respectively. From the enprofylline group 29% were withdrawn from the study due mainly to headache and nausea/vomiting and from the theophylline group 7% were withdrawn due mainly to nausea/vomiting. Mean plasma concentrations of enprofylline were 2.0 mg l-1 and 3.4 mg l-1, and with theophylline 5.4 mg l-1 and 10.0 mg l-1 at the end of periods 1 and 2, respectively. Enprofylline and theophylline produced similar improvements in lung functions and symptoms of chronic obstructive airways disease, but enprofylline was less well tolerated than theophylline. PMID- 2218009 TI - Allergic Aspergillus sinusitis: an Indian report. PMID- 2218010 TI - Tension pneumothorax and empyema as a consequence of gastro-pleural fistulae. PMID- 2218011 TI - Diffusing capacity in pulmonary embolism. PMID- 2218012 TI - [The Revista Cubana de Enfermeria has reached its 5th year of work]. PMID- 2218013 TI - [The nurse's work in the care plan for families in the mountains]. AB - In this investigation is demonstrated that the nurse needs, in order to carry out a successful work, to learn about the composition of the population of the area under her care. In Patana, a Maisi municipality with 165 inhabitants, 93 male and 72 females, prevailing ninth grade school level and an initial low hygienic culture level, which is considered as regular at the present time, intestinal parasitism and malnutrition are the main diseases in the zone. It is well demonstrated that there is a wide relationship between hygienic conditions at home and community and the incidence of the fore-mentioned diseases and that the educational work performed by the nurse in the area under her care exerts a positive influence, but the support of grassroot mass organizations is required. PMID- 2218014 TI - [The level of knowledge about different aspects of health of the population served in the Pedro Borras health area in the city of Pinar del Rio]. AB - A prospective study in order to determine level knowledge of the population about health, before and after the implantation of the Integral Medical Attention Programme to the Family, was carried out at the outpatient services in the "Pedro Borras" Teaching Community Polyclinic Health Area. Of the population attending to this outpatient area, 917 individuals older than 15 years, were selected at random. These individuals were surveyed at the beginning of the study (November 1986), in order to collect data of main necessary aspects that the population must be acquainted with on health condition and health promotion, and were surveyed again after six months of the performance of the system (May 1987), and results of both surveys were compared and shown in tables with statistical data. The main programmes for health promotion before the implantation of the new system were, known, effectively, by the population in ratios ranging 0.26-0.49. After the performance of the new programme it was observed how the level of knowledge raises to 0.31-0.70, and knowledges on obesity and sedentary habits (0.69) and on prevention of accidents (0.70) becomes significative. We consider all these changes depending on a greater educational work by the physician and nurse in charge of the plan. PMID- 2218016 TI - [Nursing care in the urticaria syndrome]. AB - A study of urticarial syndrome is carried out at the "Ciro Redondo Garcia" Municipality General Hospital, Artemisa. The clinical history of children hospitalized during 1988 in the Miscellaneous Ward were reviewed. Nurse care is valued. It was found that 9.4% of hospitalization corresponded to such disease and that urticaria was the most frequent form of presentation and in the group aged 5-14 years. Mean hospital stay was 5 years. Food was the prevailing cause of this disease and there was not chronic clinical forms. PMID- 2218015 TI - [Nursing and the smoking habit]. AB - A survey of 323 students from the first, second, and third year of Baccalaureate Nursing of the Higher Institute of Medical Sciences of Havana is made. A questionnaire is used for identifying the prevalence of smoking according to sex, age, marital status, and schooling. It is concluded that there is a high prevalence of smokers in this group. Recommendations are made. PMID- 2218017 TI - [Professor-student relations in teaching-educational development and its influence on the formation and development of the qualities of the communist personality]. AB - A research is carried out at the Polytechnic Health Institute, Psychiatric Hospital, Havana, surveying 48 students of Plan III General Nursing, in order to analyze relationship between professors and students, their influence on the development of educational-teaching process and acquisition of behavioral habits by the student, according to: professor-student relationship; professor-student reliability; influence of the professor on the formation of habits, discipline and right behaviour; place where influence of professor is exerted; influence of professor-student relationship on quality of classes; influence of professor on students' tasks, and opinions about how the image of professors is and how must be. An information that will allow us to raise the quality of educational teaching process as result of a harmonious relationship between professors and students, was obtained. PMID- 2218018 TI - [Psychogeriatrics and psychoballet]. AB - Third age within humanity has a very important place at world level and it is 11% of total population in our country. Because of the importance that our Ministry of Public Health gives to this determined population move us to carry on this paper, therefore, 26 psychogeriatric patients were selected at random, to who direct attention was offered in elemental ballet techniques. These patients are under the medical care required because of their mental affection, but they also attend to the occupational therapeutical area at the Psychiatric Hospital, Havana, where an adequate therapeutical treatment is given to them, from Monday to Friday at 8:00 a.m. until 10 a.m., and during the year in the performance of this activity we were able to observe a remarkable improvement in such patients, who have improved their interpersonal relationships, and doses of psychopharmaceuticals have been decreased. PMID- 2218019 TI - [The work of the Villa Clara Cardiac Center and the participation of the nurse in the surgical unit]. AB - The work carried out in the Cardiocenter, in Villa Clara, during the period comprised from October 1986 to October 1987, is related in this paper. Statistical data were taken from the Service of Cardiovascular Surgery, expressing them in tables with analysis given in percentage. Opinions of the working team, which allowed us to research Nursing Care during the transoperative period, as well as some considerations that must be fulfilled in the operating rooms of this type of unit, were collected and enriched such aspects with bibliographies on the theme. Results obtained and the most frequent complications are stated. PMID- 2218021 TI - [Nursing bottle caries]. PMID- 2218020 TI - [Multiprogrammable pacemakers. Complications. Nursing care]. AB - This paper deals with the study of 927 patients of both sexes, with multiprogramable pacemakers implanted during 1987-1988 period, at the "Comandante Manuel Fajardo" Teaching Hospital and the Institute of Cardiology and Cardiovascular Surgery. Complications accounted for 14.9% and the most frequent were, in decreasing order, as follows: sepsis of the pocket (46.7%), hematoma of the pocket, increased threshold and, in a lower percentage, aseptic necrosis (5.7%). Emphasis is made in the role of the nurse in front of a patient with pacemaker and of the different complications presented. PMID- 2218022 TI - [Fluoride in preventive cariology]. PMID- 2218023 TI - [Constitutional slow growth with delayed adolescence, presentation of 3 clinical cases]. AB - Constitutional delay of growth and puberty is a constitutional delay of growth occurring in otherwise healthy adolescents with stature reduced for chronological age but generally appropriate for bone age and stage of pubertal development, both of which are usually delayed; psychological distress is the predominant consequence. The analysis of three cases shows that hand and wrist X-ray to study bone age is very important in patients with short stature, because we can make a better orthodontic treatment due to this bone age delay. The maturation stage investigation can be made in both hands because there are not significant differences between right and left one. PMID- 2218024 TI - [Role of Actinobacillus actinomycetemcomitans in human infection]. AB - Actinobacillus actinomycetemcomitans (AA), is a cocobacillus thin and small, non motile, uncapsulate and capnophilic. AA, is: one of the species encountered in the mouth's comensal flora being able to be isolated in gingival crevices culture and oral mucosa in a 20% of the healthy population. An important number of pathogenic factors make it well equipped, to protect itself from host's defense mechanisms, and to destroy the periodontal tissue. Between the most important we find lipopolisacarides and leucotoxines which promote tisular invasion and destructive qualities of this microorganism. Since 1912, there are numerous reports of infectious process associated to it, between which we find: endocarditis in native and prothesic valve, soft tissues abscess, pneumonia, brain's abscess, urethritis, vertebral osteomielitis, thyroid's abscess, pericarditis and periodontal juvenile illness, being this one in which its isolation is more frequent. In vitro, AA is very susceptible to tetracicline. This antibiotic reaches high concentrations in gingival crevices, has significant affinity to the alveolar bone and contributes to protect the collagen. These special feature make them the election drug in periodontal disease produced by this microorganism. PMID- 2218025 TI - [Computerization and dentistry]. PMID- 2218026 TI - [Restorative treatment in pediatric dentistry]. PMID- 2218027 TI - [Effect of fluoridated dentifrice on root and coronal caries in a group of older adults]. PMID- 2218028 TI - [Preventive plan for orthodontic patients]. PMID- 2218029 TI - The acute effects of dexamethasone on some haematological parameters and serum biochemistry in the camel (Camelus dromedarius). AB - The effects of dexamethasone at different dose regimens on some haematological parameters and serum biochemistry were studied in the camel. Dexamethasone increased the serum concentration of glucose as well as neutrophils and total leukocyte count in the blood. Conversely, the serum concentrations of potassium and phosphorus and lymphocyte count in blood were decreased by dexamethasone treatment. Dexamethasone, however, had no effect on the activities of CPK and gamma-GT, on the serum concentrations of creatinine, BUN, total bilirubin, cholesterol and Na and on PCV, Hb, ESR, MCV and MCHC values. PMID- 2218030 TI - [Descriptive epidemiology of Rift Valley fever in small ruminants in Southern Mauritania after the 1988 rainy season]. AB - Epidemiological investigation on Rift Valley fever in small ruminants was carried out in Southern Mauritania after 1988 rainy season. Relationships were found between the incidence rate and the edaphic and climatic parameters. Propositions are made to study epidemiology of this disease in this area. PMID- 2218031 TI - [Seroconversion to bovine respiratory syncytial virus in goats with pneumonia in Zaire]. AB - Coupled sera were taken among goats suffering from pneumonia in Zaire. The presence of antibodies to bovine syncytial respiratory virus was investigated by a seroneutralization test. Out of 26 animals, 9 already had antibodies at the time of the first blood sampling, 9 presented a seroconversion and 8 remained seronegative during the two months of observation. These results suggest it would be useful to study the frequency of the infection of small ruminants with this virus and its clinical and economical impact in Central Africa. PMID- 2218032 TI - [Prevention of cowdriosis and cases of sheep diseases in the Niayes region of Senegal]. AB - Sheep originating from an heartwater-free area were immunized by the infection and treatment method, using long-acting oxytetracycline. The animals were then exposed, together with control sheep to natural infection in an enzootic area. Tick counts were made to monitor the infestation and establish a correlation between infestation by certain tick species, in particular Amblyomma variegatum, and the occurrence of cowdriosis. In some cases of death associated with ehrlichiosis and anaplasmosis in the group immunized against cowdriosis, groups of Cowdria ruminantium were found in smears of the cerebral cortex, which leaves question marks as to the real nature of immunity to cowdriosis. Furthermore, these losses show the necessity of an integrated approach to the control of diseases of livestock in a given area. The presence of Rhipicephalus e. evertsi, formerly absent from this area, was significant in this respect. PMID- 2218033 TI - Serological prevalence of bovine leptospirosis in Plateau State, Nigeria. AB - Serum samples obtained from 1.537 cattle in the 14 local government areas (LGAs) of Plateau State of Nigeria were screened for the presence of leptospiral antibodies using 13 serovars in a modified microscopic agglutination test (MAT). Two hundred and twenty-two (14.4 p.100) of the cattle tested had leptospiral antibody titres of 1:100 or higher to one or more of the test antigens. The prevalence rates of antibodies to individual serovars were: hardjo (35.6 p.100), pomona (11.7 p.100), pyrogenes (11.7 p.100), canicola (9.5 p.100), grippotyphosa (7.7 p.100), bratislava (5.9 p.100), icterohaemorrhagiae (5.9 p.100), ballum (4.5 p.100), autumnalis (3.6 p.100), bataviae (2.3 p.100) and tarassovi (1.8 p.100). The serological prevalence of bovine leptospirosis in the various local government areas of Plateau State of Nigeria differed significantly (P less than 0.05; X2). PMID- 2218034 TI - [Clinical note on an outbreak of foot rot in N'Dama cattle imported from Senegambia into Gabon, at the Ngounie ranch]. AB - The author reports the observations on an outbreak of foot rot among N'Dama cattle imported from Senegambia into Gaboon, at the Ngounie's ranch, during November 1987. The rate of morbidity is high and economic losses are not negligible as well as therapeutic costs. PMID- 2218035 TI - [A note on the first case of dry gangrene of the limbs in cattle, caused by Salmonella typhimurium in Ghana]. AB - Ischaemia and terminal tissue dry gangrene are among the sequels of Salmonella infection. Up to now, these lesions had been described in Europe and in Chile, on calf exclusively. This time, the syndrome was observed on adult cattle reared in the Accra Plains (Ghana) and infected by S. typhimurium. This case give evidence of the spreading of salmonellosis on the African continent and should foster the search of adequate control measures. PMID- 2218036 TI - Prevalence of mastitis in imported Friesian cows in Sudan. AB - Three hundred twenty-two lactating Friesian cows were examined for mastitis by different diagnostic techniques. The predominant pathogens encountered were Staphylococci, Streptococci, Corynebacterium and Escherichia coli spp. PMID- 2218037 TI - Preliminary observations on ovine paratuberculosis (Johne's disease) in Zambia. AB - In an imported flock of sheep from South Africa, an ewe became partially anorexic and gradually losing weight and conditions. The paratuberculosis (Johne's disease) was confirmed on clinical, faecal and histopathological examination. Cultural examination remained doubtful. Serological investigation of other sheep in the flock and at other farm reacted to antibodies of Mycobacterium paratuberculosis on complement fixation test. The study suggests that the disease is actively spreading. This is the first report of ovine paratuberculosis in the Republic of Zambia. PMID- 2218038 TI - [Ticks and hemoparasitic diseases in cattle in Senegal. IV. The southern Sudan area]. AB - The authors report on the results of an investigation on ticks and hemoparasitoses of cattle, sheep and goats in the South Sudanian area of Senegal. Systematic routine dipping against ticks of cattle, 40 sheep and 40 goats was set during 15 months, with a view to determine the population dynamics together with an acurate localization of the different species concerned. The following parasites were collected from these ruminants: Amblyomma variegatum, Boophilus geigyi, Hyalomma truncatum, H. m. rufipes, Rhipicephalus lunulatus, Rh. sulcatus, Rh. e. evertsi, Rh. senegalensis. At the same time joint research was conducted on hemoparasitoses by mean of blood smears and of splenectomy. In cattle were found Theileria velifera, Th. mutans, Anaplasma marginale, Babesia bigemina, Ehrlichia bovis, and microfilaria of Setaria labiatopapillosa. Anaplasma ovis, Theileria ovis, Ehrlichia ovina, Trypanosoma vivax, T. congolense are involved in infections detected in goats and sheep. Among grown up and found apparently healthy animals, the hematocrite values have been studied as well as the seasonal variations of the haematological parameter. PMID- 2218039 TI - [Blood biological constants in the deer Rusa (Cervus timorensis russa) in New Caledonia. I. Hematologic constants]. AB - Since the beginning of year 1987, the deer "Rusa" breeding has been developing in New Caledonia. In 1988, during a slaughter operation amidst the herds, nearly ninety blood samples were collected in order to define the blood biological parameters (or constants) of this species. Regarding haematology, the study concerns the following parameters: erythrocyte count (9.32 x 10(12)/l), leucocyte count (4.51 x 10(9)/l), various leucocyte lines and their formula, i.e. (neutrophile polymorphonuclear: 2.08 x 10(9)/l [46.6 p. 100]; lymphocytes: 1.75 x 10(9)/l [38.4 p. 100]; monocytes: 0.33 x 10(9)/l [7.5 p. 100]; eosinophiles polymorphonuclear leucocytes: 0.4 x 10(9)/l [7.46 p. 100]; basophile polymorphonuclear leucocytes: 0.01 x 10(9)/l [0.28 p. 100]), hematocrite (36.8 l/l), hemoglobin ratio (14.1 g/dl), mean corpuscular volume (40.3 dl), mean corpuscular hemoglobin rate (15.3 pg/cell), mean corpuscular hemoglobin concentration (38.7 g/dl). In the course of the study, variations of these parameters were detected according to various physiological criteria and to the sampling conditions as deer is a stress sensitive animal. PMID- 2218040 TI - [Blood biological constants in the deer Rusa (Cervus timorensis russa) in New Caledonia. II. Biological constants]. AB - Since the beginning of the year 1987, the deer "Rusa" breeding has been developing in New Caledonia. In 1988, during a slaughter operation in the herds, nearly 90 blood samples were collected in order to define the blood biological parameters (or constants) of this species. As for biochemistry, the following parameters have been search for: urea (6.8 mmol/l), creatinin rate (151.7 mmol/l), the activity of the creatin kinase (295.2 U/l), transaminase (ALAT: 60.1 UI/l; ASAT: 22.3 UI/l) and alcalin phosphatases (115.1 U/l), total bilirubin rate (2.76 mumol/l), total proteins rate (61.4 g/l) and albumin (32.6 g/l), calcium (2.42 mmol/l) and phosphorus (3.08 mmol/l). In course of the study, fluctuations of these parameters were detected, according to various criteria and to sampling conditions. PMID- 2218041 TI - [Clinical evaluation of Plax. Its efficiency in reducing supra-gingival plaque]. AB - A double-blind, controlled, parallel desing clinical trial was conducted to determine the affect of PLAX prebrushing rinse on supra gingival plaque levels. The results of this study suggest that using PLAX as prebrushing rinse is the same as using a placebo. PMID- 2218042 TI - [Sensitivity of the tooth cervix. A new therapeutic alternative]. AB - The cervical hypersensitivity tooth was analysed and treated by application of a varnish with high fluoride ions content (Duraphat) and of a glass ionomer cement usually indicated to cavity lining (XR-ionomer-Kerr). This technique was applied in sixty-seven teeth of Clinic Graduation patients (Faculdade de Odontologia de Aracatuba) and demonstrated a high index of satisfactory results. The clinical findings of this study relate that, this technique is more one method of choose by clinicians. PMID- 2218043 TI - [Methods of X-ray protection. Comparative analysis of conditions of radiographic protection utilization by dental professionals]. AB - In this work, the authors examined the condition and uses of the relation to radiation protection. The authors personally gave a questionnaire to about seventy dentists, of all specialities marking up almost 12% of the dentists of the state. This questionnaire was compared to other questionnaires from Sao Paulo and Joao Pessoa cities. According to the data obtained we can present the following conclusion: The acknowledge level of safety in relation to radiation protection with patients, dentists and attendants here is similar to Sao Paulo city but this below standard. A better understanding and stricter observation of the recommendation of FEDERATION DENTAIRE INTERNATIONALE is necessary. PMID- 2218044 TI - [Relationship between growth and tooth eruption. Relationship between growth and physical development and eruption of first permanent molars in Sao Paulo students]. AB - In order to verify the relationship between the children's growth and their teeth's emergence the authors surveyed 1278 school children in Sao Paulo's Ipiranga District, 1024 from government controlled schools and 254 from a private school, finding their weight and height anthropometric measures related to the emergence of permanent molars. Their ages were four (completed) to eight incompleted). It was verified that the children from the private school presented in average higher weight and height than those from government controlled schools as well as higher percentages of first permanent molars erupted, in both the sexes and in all the age groups and that there was a positive association between the children's growth and their teeth's emergence. PMID- 2218045 TI - [Incidence and treatment of cysts]. AB - The records of 78 patients (1978-1987 period) submitted to surgical treatment of cysts, were analysed to verify the cyst location, etiology, types of cysts, and surgical techniques. There were made commentaries and orientations on the necessity of radiography, cytological and histopathological examination and post operative radiological control. PMID- 2218046 TI - [Total crowns in natural teeth]. PMID- 2218047 TI - [Perforating internal resorption of the root. Surgical treatment using a hybrid obturation technic]. AB - This article relates a clinical case of internal root resorption with root perforation treated with a new surgical proceeding. The Tagger et alii technique was used for root canal filling and root resorption area. PMID- 2218048 TI - [Atypical total implants for screws]. AB - By screws total, atypical implants. For cases of total edentates, the author relates and commends the use of endosseous screws not parallel between themselves, but unites by a small bar or threads of soldered titanium. Thus on this created "wall" the prosthesis is finished and fixed. Illustrative cases are presented. PMID- 2218049 TI - [Indirect bonded prosthesis. Use of an impacted central incisor]. AB - The authors presents a case about right central superior incisor impacted. After surgical remotion of the retain tooth, this was utilized like pontic in the confeccion of the indirect adhesive prosthesis for the patient. PMID- 2218050 TI - [Influence of static flow (CREEP) on amalgam hardness. Effect of alloys and measured areas]. AB - The authors studied the CREEP of 5 amalgam alloys (1 conventional and 4 with high cooper) by the application os static load of 36 MPa in 478 mm specimens, 7 days old. After CREEP test, the samples were included in acrylic resin and Vickers hardness determined by three penetrations for each portion (cervical, medium and occlusal). Samples not submitted to the creep test was used with control. They concluded that no statistic difference was found in creep test but in Vickers test all the studied materials showed different hardness averages. The load application to samples increased the hardness of all the studied materials. PMID- 2218051 TI - [Anterior open bite. Concept, etiology, characteristics, classification and clinical cases]. AB - The preoccupation with vertical abnormalities, and particularly anterior open bites, led the authors to establish its concept, to review the literature concerning aetiology and treatment, to propose a classification and to present three case reports of this condition. PMID- 2218052 TI - [Esthetics in metal-ceramics]. AB - A rational and simple esthetical guideline is presented; In order to obtain this aim, seven steps are suggested. PMID- 2218053 TI - [Dentinal surface of root canals. Study of human permanent upper central incisors, using scanning electron microscopy technic]. AB - Dentinal surfaces of the root canal in the human permanent incisors were studied by using scanning electron microscope. The teeth were sectioned and fractured longitudinally. Dehydration were made in ethanol, dried, coated with gold and examined in a Jeol scanning electron microscope. The results revealed that the dentinal surface of the root canal of central upper incisor presents numerous foraminae of dentinal tubules. These possess variable diameters being that the smallest ranges from 1 to 2 microns and the greatest ranges from 2.5 to 4 microns. The intertubular dentinal surface is uniform in aspect and the peritubular dentine show several lines on the walls. PMID- 2218054 TI - [Determination of centric relation. Study of the lateral position of the mandible in relation to the facial median line, using 2 methods of determination]. AB - The authors studied the lateral positional desviations of the mandible, in relation to the facial median line in 30 (thirty) full edentulous patients, with the purpose to verify the influence of the unstrained guided (chinpoint guidance) and deglutition methods for the determination of centric relation. According the results obtained they conclude that the unstrained guided method produced a mandibular lateral desviation with a mean value of the 0.752 mm and in the deglutition method the mean value observed was 1.109 mm. The statistical analysis of the results revealed for the unstrained guided method a proportion of the "points" to the right and left of the median line not statistically significant, while for the deglutition method the difference was statistically significant at a level of 5%. PMID- 2218056 TI - Immune-associated abortion: human vs mouse model. PMID- 2218055 TI - Modulation of gut wall paf-acether and precursors by intestinal microflora. AB - Comparison between holoxenic and axenic mice led to the conclusion that the presence of an intestinal microflora produced a decrease in wall paf in conventional mouse caecum, whereas an increase in wall lyso-paf and alkyl-acyl glycerophosphocholine (A-A-GPC) content was noticed. By contrast, the presence of flora had no significant incidence on wall paf, lyso-paf and A-A-GPC content of conventional mouse jejunum. Thus, the modulation of gut wall phospholipid composition by intestinal microflora is evidenced for the first time. PMID- 2218057 TI - On "the immunology of spontaneous abortion". PMID- 2218058 TI - Additional arguments for the key role of "smart" autolysins in the enlargement of the wall of gram-negative bacteria. AB - Because the wall of Gram-negative bacteria is thin, the mechanism for safe enlargement of the cell is subject to strong constraints. Several models for wall growth have been proposed; in the order that they have been proposed, these include: 1) an "allosteric" model in which the critical autolysin is only functional if the bond to be cleaved is near a covalently cross-linked, but unstretched oligopeptide; 2) a model in which the cell wall is thick enough to enlarge by the "inside-to-outside" mode characteristic of Gram-positive rods; 3) a "patches" model, recently proposed by Holtje, in which only parts of the cell wall are thickened at any one time; 4) a new multienzyme model in which the transpeptidase/autolysin complex cleaves one cross-linked oligopeptidoglycan chain for every two nascent chains covalently polymerized to the sacculus. These models are considered and contrasted. While none can be rigourously excluded, no. 4 is favoured. All models as applied to the Gram-negative rod-shaped bacteria require special, extraordinary features for their autolysins. These features have not been found with any other class of enzymes, but are essential to permit safe cell expansion. PMID- 2218059 TI - Immunolabelling of Shiga toxin in macrophages infected with Shigella dysenteriae 1. AB - Immunolabelling of Shiga toxin in macrophages infected with a non-invasive Shigella dysenteriae 1 isolate showed that bacteria remained alive for 3 h after ingestion within the phagocytic vacuole and synthesized Shiga toxin. The normal process of toxin secretion was, however, impaired by the phagosomal environment and toxin molecules accumulated within the bacterial cytoplasm. PMID- 2218060 TI - Characterization of Mycobacterium paratuberculosis and "wood-pigeon" mycobacteria by isoenzyme profile and selective staining of immunoprecipitates. AB - Cell-free extracts of various strains belonging to Mycobacterium paratuberculosis (Ptb) and "wood-pigeon" (WP) mycobacteria were compared by polyacrylamide gel electrophoresis and the various protein bands obtained were tested for peroxidase enzyme activity. One strain of Mycobacterium avium served as a control. Bacterial extracts were also analysed by crossed immunoelectrophoresis (CRIEP) and fused rocket immunoelectrophoresis (FRIEP) using antisera raised in rabbit against M. paratuberculosis and WP mycobacteria. The immunoprecipitates obtained both in CRIEP and FRIEP plates were subsequently stained for selective peroxidase enzyme staining. Our results showed that, although Ptb and WP mycobacteria shared common peroxidase isoenzymes and antigens, they also had specific immunoprecipitates showing the differences between the two groups of bacteria. PMID- 2218061 TI - Competitive erythroimmunoassay for detecting Clostridium perfringens type A enterotoxin in stool specimens. AB - A competitive erythroimmunoassay (ERIA) is described for Clostridium perfringens enterotoxin (CPE) detection in stools. This technique uses sheep red blood cells sensitized by CPE and an anti-CPE-antibody-coated plate in which the results are read by eye. ERIA is simple, rapid, economic and more sensitive (2 ng/ml) than the enzyme-linked immunosorbent assay used for evaluation. ERIA is suitable for CPE detection in stool samples protected with phenylmethylsulphonylfluoride. PMID- 2218062 TI - Utilization of aromatic substances by Azotobacter chroococcum. AB - Azotobacter chroococcum utilized catechol, protocatechuic acid and gentisic acid as sole carbon source. Rothera's test indicated the ortho cleavage of phenols. The cells displayed high levels of dioxygenase activity. Catechol was cleaved by the ortho pathway mediated by catechol 1,2-dioxygenase. Protocatechuate and gentisic acid were also cleaved by the ortho pathway and cells grown in protocatechuate and gentisic acid displayed protocatechuate, 3,4-dioxygenase and gentisate dioxygenase activity, respectively. PMID- 2218063 TI - [Chemotaxonomy of gram-positive bacteria metabolizing beta-caryophyllene]. AB - Chemotaxonomic identification of coryneform bacteria metabolizing b-caryophyllene was attempted. The following phospholipids were identified as main components of the bacterial extracts: cardiolipids, phosphatidylethanolamine, phosphatidylinositol and mannosides of phosphatidylinositol. Saponification of the lipid extracts gave a mixture of hydroxylated and nonhydroxylated fatty acids. Among the latter, oleic and tuberculostearic acids were identified. The hydroxylated fatty acids were analysed by thin-layer chromatography and mass spectrometry (as methyl esters). From the results thus obtained, the strains appeared to be more closely related to the genus Rhodococcus than to the genus Nocardia. PMID- 2218064 TI - Effects of static magnetic fields on membrane permeability of a cultured cell line. AB - To clarify the effects of magnetic fields on plasma membrane permeability of "living cells", we measured the accumulation and efflux of adriamycin (ADR) in a cell line, TALL-1, using flow cytometric techniques. The amount of ADR accumulated in the cells for 15 minutes under a static magnetic field (0.4 Tesla(T), 1T = 10000 gauss) was less than 5-10% that in the control cells without magnetic fields within a temperature range of 41-46 degrees C corresponding to the phase transition temperature. It is interesting that ADR efflux from magnetic field-exposed cells increased compared with unexposed cells at 41-44 degrees C. These results suggest that lipid clustering, which occurs at the phase transition temperature, may take place in "living cells" as well as in artificial membranes and play an important role in increasing the ADR efflux from the cell membrane under magnetic fields. PMID- 2218065 TI - Enhancement of skeletal muscle fatigue by the calcium channel antagonist diltiazem. AB - This study sought to determine the effects of diltiazem on normal muscle twitches and on twitches evoked during repetitive stimulation. Initial experiments showed that diltiazem (5 and 30 microM) had slight, but insignificant, effects on peak twitch tension and the time course of the twitch. When muscles were stimulated at 1 or 5 Hz, 30 microM diltiazem significantly depressed the height and time course of the staircase period and increased the rate and magnitude of fatigue. Contrary to control, diltiazem caused a complete loss of developed tension during both stimulation protocols. Results suggest that although diltiazem has little effect on single twitches, it has marked inhibitory effects on twitches evoked during repetitive activity; the result being enhancement of the fatigue process. PMID- 2218066 TI - Prevention of acetaminophen-induced hepatotoxicity by endotoxin in mice. AB - A preliminary trial was conducted to determine if endotoxin would prevent acetaminophen (APAP)-induced hepatic toxicity. When mice were pretreated with endotoxin (1, 2 and 4 mg/kg, i.p.), the clinical chemistry profile and pathological alterations caused by APAP were reduced with a dose dependent manner. The efficacy of endotoxin in preventing APAP-induced hepatic necrosis should be further studied. PMID- 2218067 TI - Isoniazid potentiation of acetaminophen hepatotoxicity in the rat and 4 methylpyrazole inhibition of it. PMID- 2218068 TI - Effects of chloroquine and hepatic stimulator substance on cellular accumulation and nuclear binding of 125I-epidermal growth factor in primary culture of adult rat hepatocytes. AB - The effects of chloroquine and hepatic stimulator substance (HSS) on cellular accumulation and nuclear binding of 125I-epidermal growth factor (EGF) were examined in primary culture of adult rat hepatocytes. When intact hepatocytes were incubated at 37 degrees C with 125I-EGF, the cellular accumulation and the nuclear binding reached a peak at 1 h and declined thereafter, where the nuclear binding was 2.49% at 1 h and 2.53% at 2 h. Chloroquine resulted in a time dependent increase in the cellular accumulation and the nuclear binding was 3.37% at 1 h and 3.72% at 2 h. In contrast, HSS produced no change in each value, suggesting that HSS does not modulate EGF receptors in plasma membrane and nucleus. PMID- 2218069 TI - The effect of phenobarbital and dexamethasone on hepatic cytochrome P-450 and alpha 1-acid glycoprotein in maternal and fetal guinea pigs. AB - The effects of phenobarbital (PB) and dexamethasone (DX) on maternal and fetal hepatic cytochrome P450 content, benzphetamine (BzP) demethylation activity, the plasma concentration of alpha 1-acid glycoprotein (AGP), and the binding of propranolol (PPL) were examined in guinea pigs. In maternal guinea pigs, PB increased AGP-specific PPL binding by 131%, P450 by 94%, and BzP demethylation by 261%. DX only increased maternal AGP-specific PPL binding (122%). In fetal guinea pigs, neither PB nor DX resulted in significant increase for any of these parameters. The combination of PB and DX synergistically increased fetal P450 content (153% increase) and BzP demethylation (84% increase). In contrast, this combination treatment did not increase maternal P450 and BzP demethylation to a greater extent than by PB treatment alone nor did it increase the binding of PPL in PCA-treated fetal plasma. The synergy of P450 induction found in the fetus implicates glucocorticoids as important regulators of fetal hepatic microsomal enzyme maturation. PMID- 2218070 TI - Comparative effects of three dithiocarbamates on tissue distribution and excretion of cadmium in mice. AB - The effects of sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), and sodium N-p carboxybenzyl-D-glucamine dithiocarbamate (CBGD), which were newly synthesized, on the distribution and excretion of cadmium were compared in mice exposed to cadmium. Mice were injected with 109CdCl2 (1 mg Cd/kg and 74 KBq of 109Cd/one animal) and 30 min or 24 h later, they were injected with the dithiocarbamates (400 mumols/kg). At 30 min after treatment with cadmium, these chelating agents significantly enhanced the biliary excretion of cadmium, and HBGD and CBGD significantly increased the urinary excretion of the metal. At 24 h after cadmium injection, BGD and HBGD significantly increased the biliary excretion of cadmium and HBGD was the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver and kidney at 30 min after cadmium treatment. HBGD showed the largest effectiveness on the depression of cadmium contents in the liver and kidney. At 24 h after cadmium treatment, only HBGD among these chelating agents significantly reduced the cadmium contents in the liver and kidney. These results show that the injection of HBGD at both 30 min and 24 h after cadmium treatment can much more effectively mobilize cadmium from the body mainly through the bile without redistribution of cadmium to other tissues, such as brain, testes, and heart, than injection of BGD and CBGD. PMID- 2218071 TI - Teratogenic effects of nitrazepam in rats. AB - The teratogenicity of nitrazepam, a benzodiazepine-type drug, was investigated in Sprague-Dawley rats. Nitrazepam was administered to pregnant females at levels of 100, 200 or 300 mg/kg in a single dose on one of gestation days 10-14. Fetuses were examined for external and skeletal malformations on day 20 of gestation. Nitrazepam was found to produce various types of malformations, i.e., exencephaly, cleft palate, micrognathia, short or kinky tail and limb reduction defects. The predominant malformation was limb reduction defects, which were produced at high frequency by treatment on day 12 or 13 of gestation. Microscopic examination of limb buds revealed hemorrhage and mesenchymal cell necrosis at 24 hours after nitrazepam treatment. PMID- 2218072 TI - Semicarbazide-sensitive amine oxidase activity in streptozotocin diabetic rats. AB - Semicarbazide-sensitive amine oxidase (SSAO) activity was investigated in serum and tissues of streptozotocin diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) and rats were killed at 1, 3, 7, 9, 14, 28 and 56 days after treatment. STZ increased serum glucose and serum SSAO activity at all time points with a maximal increase (2 to 3 fold) at day 7. Kidney SSAO activity showed significant increases on days 9 and 14 (2.5 and 4 fold, respectively). SSAO activity of aorta, lung and pancreas was not changed significantly. Kinetic analysis showed that the elevation in both serum and kidney SSAO activity was due to an increased Vmax with no change in Km. SSAO activity appears to be selectively increased in the serum and kidney of STZ diabetic rats which may be indicative of a relationship between serum SSAO and early renovascular damage in this animal model of diabetes mellitus. PMID- 2218073 TI - In vitro interaction of mercury, copper (II) and cadmium with human glutathione transferase pi. AB - The in vitro interaction of mercury, copper (II) and cadmium with human glutathione transferase (GST) pi was studied using reduced glutathione (GSH) and 1-chloro-2,4-dinitrobenzene as substrate. Tumor specific human GST pi was isolated from the human hepatoma derived PLC/PRF/5 cell line. The inhibition of the GST pi activity was dose dependent. Kinetic studies never revealed competitive inhibition. A parabolic inhibition was found with GSH as the variable substrate. The heavy metals are spontaneously conjugated with GSH and cysteine, but interact with GST pi by direct binding to this protein. This binding could have a protective function against heavy metals. PMID- 2218075 TI - Transcatheter arterial embolization and chemoembolization induce the production of free radicals in the normal rat liver. AB - Superselective transcatheter arterial embolization (TAE) of the left and median lobes of the normal rat liver was performed using gelatin sponge (1.5 mg/ml). Superselective transcatheter arterial chemoembolization (TAC) of the same lobes was done adding mitomycin (MMC) at a dose of 1.6 mg/ml to the embolic solution. In another group of rats MMC alone was injected intraarterially into those lobes. It was found that both embolic procedures and the arterial injection of MMC decrease the hepatic total glutathione content. Glutathione peroxidase activity and alpha-tocopherol content remained unchanged. Lipoperoxides were detected 3 and 6 h after TAC in chemoembolized and non-chemoembolized lobes. Similar findings in both injected and noninjected lobes were found after MMC injection. The TAE lobes only showed elevated lipoperoxide content 6 h after embolization, this parameter remained unchanged in the non-TAE lobes. These findings suggest that free radicals are formed after TAE, and that the addition of MMC to the embolic solution increases the oxidative attack and/or that the oxidative reactions after TAC are mainly mediated by lipid peroxidation due to the presence of MMC. PMID- 2218074 TI - Systemic anaphylaxis--separation of cardiac reactions from respiratory and peripheral vascular events. AB - An anaphylactic reaction in the isolated perfused heart is characterized by a drastic coronary constriction, arrhythmias, and an impairment of contractility. In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to ascertain the electrocardiographic and cardiovascular changes during systemic hypersensitivity reactions. In addition, an attempt was made to differentiate cardiac from respiratory events. In guinea pigs, sensitization was produced by s.c. administration of ovalbumin together with Freund's adjuvant solution. Fourteen days after sensitization, the effects of an i.v. infusion of ovalbumin were tested in the anesthetized guinea pigs, which were ventilated with room air or 100% oxygen. A second administration of the antigen induced the development of cardiovascular collapse, leading to death within 12 min. Within 3 min, cardiac output decreased by 90% and end-diastolic left ventricular pressure increased significantly, indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in the form of atrioventricular block. Left ventricular contractility declined continuously within the first 4 min. Finally, after 4 min, blood pressure steadily decreased. During ventilation with room air, severe hypoxia developed, with arterial PO2 decreasing from 94 mmHg to 14 mmHg after 3 min. However, under ventilation with 100% oxygen, a dissociation between cardiac damage and respiratory distress occurred. Myocardial ischemia and signs of cardiac failure preceded the development of hypoxia by a significant time interval. It is to be concluded that cardiac damage is a primary event in anaphylactic shock. Furthermore, the electrocardiographic signs of ischemia are interpreted as a result of coronary artery spasm. PMID- 2218076 TI - Temperature-induced shape transformation of carrier erythrocytes. AB - Erythrocytes have been proposed as cellular carriers for enzymes and drugs for protected delivery, slow release, or targeting to specific organs. Several studies have established the heterogeneity of resealed carrier erythrocytes concerning various characteristics, including morphology. Carrier erythrocytes were prepared by hypo-osmotic dialysis and consecutive iso-osmotic resealing at different temperatures, and the morphology of these cells was studied by scanning electron microscopy. Different cell shapes could be prepared by temperature variations during resealing or incubation. All intermediate shapes of echinocytosis were observed at low temperatures or with depleted energy supply but could be reversed to biconcave discocytes. Resealing at 4 degrees C resulted in highest percentage of echinocytes III, spherocytes, and leaky cells. Spontaneous resealing of 20% of the cells was obtained at high lysis temperatures. Combining low temperatures for lysis and high temperatures for resealing and sufficient energy supply are advantageous for highest recovery of biconcave discocytes. Shape of the erythrocyte, is the result of divergent forces, and temperature during resealing was found to be an important factor. PMID- 2218077 TI - Beta-alanyl-L-histidinato zinc prevents skeletal unloading-induced disorder of bone metabolism in rats. AB - The effect of a new zinc compound beta-alanyl-L-histidinato zinc (AHZ) on the disorder of bone metabolism caused by skeletal unloading was investigated. Skeletal unloading was designed using the model of hind-limb hang in rats. Skeletal unloading for up to 4 days caused a remarkable decrease of zinc content, alkaline phosphatase activity, and DNA content in the femoral diaphysis of rats. Oral administration of AHZ (2.5, 5.0, and 10.0 mg/100 g) caused a significant increase in zinc, DNA, and calcium contents in the femoral diaphysis of rats with the skeletal unloading. Bone alkaline phosphatase activity was significantly increased by doses of 5.0 and 10.0 mg/100 g. These results clearly indicate that skeletal unloading-induced disorder of bone metabolism is prevented by the oral administration of AHZ. AHZ may be useful as a therapeutic tool in bone disorder. PMID- 2218078 TI - Aging affects cellular zinc and protein synthesis in the femoral diaphysis of rats. AB - To clarify the effect of aging on bone metabolism, alteration of the cellular zinc content and protein synthesis was examined in the femoral diaphysis of 3- and 30-week-old male rats. The cellular zinc content in bone tissue markedly decreased in 30-week-old compared to 3-week-old rats. When the bone tissue from older rats were cultured with [3H]leucine, incorporation of [3H]leucine into the acid-insoluble residues was less than for weanling rats. This decrease was partly restored by the oral administration of zinc sulfate (0.5, 1.0, and 2.0 mg Zn/100 g body weight) to elderly rats for 3 days. An increase of in vitro [3H]leucine incorporation by bone tissues obtained from the rats that had received zinc (2.0 mg/100 g) was blocked by cycloheximide (10(-6) M) or dipicolinate (10(-3) M), a chelator of zinc. These results suggest that bone protein synthesis declines with age, and that this decline may be based partly on the decrease in bone cellular zinc. PMID- 2218079 TI - Experimental analysis of gastric mucosal blood flow after transient forebrain ischemia. AB - Gastric mucosal blood flow (GMBF) was measured by a laser doppler flow meter continually during and after transient forebrain ischemia in rats. The value of GMBF obtained after at 15 min of ischemia did not change significantly compared to that of the preischemic period. However, a 26% decrease of GMBF was detected after 30 min of ischemia. When circulation of the brain was restored, the GMBF increased slightly after 15 min. After 30, 45, and 60 min of restored cerebral circulation, the GMBF decreased significantly and the values were 63%, 58% and 51% of the control, respectively. PMID- 2218080 TI - [Recent advances in pulmonary surfactant research with special reference to surfactant apoproteins]. PMID- 2218082 TI - [Recent elucidation of the genetic defects among disease of the chest: cystic fibrosis, chronic granulomatous disease, and alpha 1-antitrypsin deficiency]. PMID- 2218081 TI - [Combination therapy of antiarrhythmic drugs]. PMID- 2218083 TI - [Central nervous in cardiac disorder]. PMID- 2218084 TI - [ACE inhibitors and cough]. PMID- 2218085 TI - [Natural history of severe aortic regurgitation and timing of the aortic valve prosthesis]. PMID- 2218086 TI - [A study on clinical and electrophysiologic characteristics of ventricular tachycardia: comparison of differences on its sustenance]. AB - The purpose of this study was to clarify the difference of clinical and electrophysiologic characteristics between sustained ventricular tachycardia (SVT) and nonsustained ventricular tachycardia (NSVT). 40 patients consisting of 24 males and 16 females with an average age of 50.0 years (range from 19 to 83), who had shown ventricular tachycardia (VT) on electrocardiogram, were studied consecutively. The patients were divided into SVT group (19 cases) and NSVT group (21 cases). Ventricular stimulation was performed up to triple extrastimuli, and ventricular burst pacing was used when required. After VT was induced, R-R interval during VT was measured and an antiarrhythmic agent was given by bolus injection. Echocardiography was used for measurement of left ventricular ejection fraction (EF) and for evaluation of mitral valve prolapse (MVP). Palpitation and oppressive sensation were dominant in SVT (84.2%), while dizziness and syncope were prominent in NSVT (57.1%). Organic heart disease (OHD) was observed in only 42.1% of SVT, and in none of NSVT. MVP was observed in 6 patients of SVT and in 5 patients of NSVT. EF was significantly higher in NSVT (67.1%) than in SVT (56.9%) (p less than 0.02), while it was not significantly different in cases of NSVT and SVT where OHD was not present (64.4%). VT was induced and sustained in 17 out of 19 patients (89.5%) in SVT by ventricular stimulation. In NSVT, VT was induced in 6 of 21 patients (38.6%), but it was not sustained in any of them. The induction of VT in NSVT appeared to require more extrastimuli than in SVT. The R-R interval in SVT was longer than in NSVT (345.9 +/- 84.6 msec and 245.0 +/- 40.7 msec, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218087 TI - [Study on the respiratory failure with cardiac failure--focus on hypoventilation respiratory failure]. AB - Respiratory failure accompanied by cardiac failure occurs mostly due to decreased PaO2. However, sometimes we encounter patients with cardiac failure having on increase of PaCO2, who develop CO2 narcosis in the ICU. In this study we evaluated hypoventilation respiratory failure in patients with cardiac failure. Seventy-six patients with both respiratory failure and cardiac failure caused by intrinsic heart disease, who required mechanical ventilation in the ICU were studied. The patients were divided into 2 groups; hypoxic respiratory failure group (n = 53) and hypoventilation respiratory failure group (n = 23). Blood gas analysis and cardiovascular hemodynamics including arterial blood pressure, heart rate and Swan-Ganz catheter findings were performed before, during and after mechanical ventilation in each patient. Mortality rate and its relation to hemodynamic variables were also evaluated in each group. In both groups even when it was possible to maintain oxygenation capacity by conducting mechanical ventilation against severe respiratory failure, what can be said about the prognosis is that it depended totally on the improvement of cardiac function. The mechanism by which hypoxemia is displayed due to cardiogenic pulmonary edema is already well known, but in regard to the mechanism of hypercapnia in cases with hypersensitivity of the airways it is thought that through induction of cardiogenic pulmonary edema bronchial spasms is induced, and this causes hypercapnia. However, it is also possible to consider cardiac asthma as the cause. Among respiratory failure cases due to cardiogenic pulmonary edema that occurs in association with heart failure, there is both hypoxic respiratory failure as well as hypoventilation respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218088 TI - [The effect of percutaneous transluminal coronary recanalization (PTCR) on late potentials detected by signal-averaged electrocardiogram in patients with previous myocardial infarction]. AB - The purpose of this study was to assess the effect of percutaneous transluminal coronary recanalization (PTCR) on late potentials (LP) in patients with previous myocardial infarction (MI). The signal-averaged ECG was recorded by Fukuda VCM 3000 in 54 patients with anterior MI (average of 32 months after onset of MI). Fifty four patients were divided into two groups: Group A was comprised of 29 patients who underwent PTCR, and Group B was comprised of 25 patients who didn't receive PTCR. Ventricular arrhythmias detected by 24 hour Holter monitoring, and left ventriculographic findings were also evaluated. The presence of LP was defined as low amplitude signals (less than 15 microV) in the last 40 msec of the filtered QRS complex. The incidence of LP was significantly higher in Group B than in Group A (32% vs 7%, p less than 0.01). The presence of PVCs and ejection fraction (EF), LV end-diastolic volume (EDV), LV end-systolic volume (ESV) and % abnormally contracting segment (% ACS) were not significantly different in each respective groups. However, ESV and % ACS were significantly larger (p less than 0.05), and EF was significantly smaller (p less than 0.01) in patients with LP (+) than in patients with LP (-). LP was present in two patients who had undergone PTCR (TIMI grade 2) unsuccessfully, whereas it was not present in the 27 patients with successful PTCR (TIMI grade 3). It was concluded that successful recanalization of the infarct-related arteries may reduce the incidence of LP. PMID- 2218089 TI - [Continuous monitoring of mixed venous oxygen saturation during exercise using fiberoptic pulmonary artery catheter]. AB - We measured the mixed venous oxygen saturation (SvO2) continuously using a fiberoptic thermodilution pulmonary artery catheter to analyze the time course of SvO2 during exercise, and evaluated the relationship between SvO2 and exercise load, SvO2 and cardiac output. Five patients with old myocardial infarction and one healthy man underwent pulmonary arterial catheterization and then performed an incremental steady state exercise test using a supine cycle ergometer. There was a rapid fall in SvO2 43.4 +/- 10.6 seconds after the start of exercise and new steady state were achieved 92.6 +/- 22.5 seconds after changing the exercise load. The value of SvO2 at exercise load 60 watts were 44.7 +/- 9.8% and this value was under the level of lactic acid accumulation. SvO2 correlates well with cardiac output by the thermodilution method in individual patients. We conclude that a fiberoptic thermodilution pulmonary artery catheter was useful to evaluate the dynamic changes of SvO2 during exercise. PMID- 2218090 TI - [Two cases of acute coronary occlusion after successful coronary angioplasty associated with a treadmill stress testing]. AB - We presented two cases of acute coronary occlusion after successful percutaneous transluminal coronary angioplasty (PTCA) associated with a treadmill stress testing. Case 1: A 54-year-old man with effort angina was referred to our hospital for cardiac catheterization. At the time of cardiac catheterization, the proximal RCA had a 99% diameter narrowing, and the proximal LCX had a 90% diameter narrowing. PTCA was performed and both lesions were successfully dilated. Eight days after PTCA, he had a symptom-limited treadmill stress testing, using the Bruce protocol. The exercise was terminated at a peak heart rate of 173/min (103% of aged-predicted maximal heart rate), and at a maximal systolic blood pressure of 140 mmHg. A few minutes after the end of exercise, he developed a severe chest pain and ECG changes, which showed ST elevation in leads II, III, aVF and ST depression in leads V4-V6. Emergency coronary angiography disclosed an acute coronary occlusion of RCA at the site of PTCA. Emergency PTCA was performed and the lesion was successfully re-dilated. Case 2: A 68-year-old man was referred to our hospital for cardiac catheterization a month after subendocardial anterior myocardial infarction. At the time of cardiac catheterization, the proximal LAD have a 99% diameter narrowing. PTCA was performed and the lesion was successfully dilated. 18 days after PTCA, he had a symptom-limited treadmill stress testing, using the Bruce protocol. The exercise was terminated at a peak heart rate of 158/min (102% of aged-predicted maximal heart rate), and at a maximal systolic blood pressure of 218 mmHg. Ten minutes after the one of 218 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218091 TI - [A case of intrapleural rupture of pulmonary arteriovenous malformation with shock]. AB - We report a case of a 59-year-old male who suddenly developed massive right hemothorax and shock due to pulmonary arteriovenous malformation (AVM). He was admitted as an emergency case because of severe back pain, cyanosis and cold sweat. Although shock with massive right hemothorax was found, echocardiographic and X-ray computed tomographic examination showed no dilatation of the aorta, no intimal flap in the aorta and no pericardial effusion which suggested aneurysm. Pulmonary arteriography, performed subsequently, disclosed intrapleural rupture of the right pulmonary AVM. The patient recovered successfully from the state of shock. The pulmonary AVM was removed by segmentectomy of the right lung (S4). He was discharged following an uneventful postoperative course. Intrapleural rupture with shock is a very rare complication of pulmonary AVM. Pulmonary AVM should be considered as one possible cause in patients with massive hemothorax and shock. PMID- 2218092 TI - [Three operated cases of LMT-lesion with chief complaint of syncopal attack]. AB - An urgent aorto-coronary bypass operation (AC-bypass) was made in three patients with unstable angina pectoris, suffering from stenosis of the left main trunk (LMT). All patients were admitted with chief complaints of chest discomfort and syncopal attack. Case 1 was a 71 year-old man who suffered with chest discomfort and syncopal attack. He was admitted to our emergency room by ambulance 40 minutes after the syncopal attack, on January 11, 1989. His blood pressure was 140/96; pulse 84 and regular. The electrocardiogram (ECG) showed right bundle branch block, ST elevation in aVR, aVL and ST depression in all other leads. Coronary arteriogram (CAG) was made urgently and showed 80% stenosis in LMT. The emergency AC-bypass operation was successfully carried out about 3 hours and 10 minutes after the onset of symptoms. Case 2 was a 51 year-old man who suffered from precordial oppression and syncopal attack. He was admitted to our emergency room by ambulance about 1 hour after the attack, on January 17, 1989. His blood pressure was 94/74; pulse 120 and irregular. Chest radiography showed a cardiothoracic ratio of 58% and the ECG disclosed atrial fibrillation, ST elevation in aVR and ST depression in I, II, III, aVF, V1-6. The echocardiogram revealed hypokinetic motion in the antero-lateral wall of the left ventricle. CAG was carried out without delay, and showed 70% stenosis with slit in LMT. An emergency AC-bypass operation was successfully carried out about 3 hours and 50 minutes after the onset of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218093 TI - [Torsade de Pointes with T wave alternans in a patient receiving moderate dose of chlorpromazine: report of a case]. AB - A case is presented of Torsade de Pointes (TDP) with T wave alternans in a 31 year-old female receiving a moderate dose of chlorpromazine. She was treated in an another hospital for schizophrenia with chlorpromazine (100 mg daily) for several years and admitted to Fujisawa city hospital for numerous episodes of syncope. The electrocardiogram immediately after admission revealed a marked QTc prolongation to 0.81 seconds, T wave alternation without any obvious change in morphology of the QRS complex, and recurrent ventricular tachycardia called TDP. The T wave alternans and TDP were easily abolished by intravenous administration of a bolus of 50 mg lidocaine infusion. The QT interval however, remained prolonged. Physical examination, including cardiac examination, was normal. Serum potassium was 3.6/mEq. Chlorpromazine was discontinued immediately after admission and no further episodes of TDP were seen after the first day. After the QT interval returned to almost normal, chlorpromazine (50 mg daily) was re administered. Two days after the re-administration, the electrocardiogram revealed marked QT interval prolongation with prominent T waves. Psychotropic drugs, such as chlorpromazine, prolong the QT interval and cause TDP. Chlorpromazine appears to have been responsible for TDP and the T wave alternans in this case. TDP caused by a moderate dose of chlorpromazine has not been previously reported. Lone T wave alternans unaccompanied by changes in the QRS complex is a rare phenomenon and the mechanism underlying T wave alternans remains unknown. PMID- 2218094 TI - Factors limiting maximal oxygen consumption in humans. AB - The factors limiting VO2max in humans are analyzed according to a multifactorial model derived from the O2 conductance equation. In this context, alveolar ventilation (VA) and lung O2 transfer (GL) are not considered to be limiting, at least at sea level, because changes in VA and/or in GL are not accompanied by changes in VO2max due to the shape of the O2 dissociation curve. Thus, the limits to VO2max are shared between blood O2 transport (FQ') and a peripheral factor. This last includes tissue O2 transfer (Ft') and mitochondrial O2 utilization (Fm'). In untrained subjects at sea level, blood O2 transport is found to be responsible for approximately 70% of the overall limits to VO2max (FQ' = 0.7), the rest depending on the peripheral factors. FQ', as well as the sum of Ft' and Fm', are unchanged after training or upon return to sea level following exposure to chronic hypoxia (altitude higher than 5000 m). In the latter condition, however, since tissue O2 transfer, which sets Ft', is facilitated, and mitochondrial O2 utilization, which sets Fm', is impaired, Ft' is reduced and Fm' increased as compared to control condition and/or after training. PMID- 2218095 TI - The different relationship of VO2max to muscle mitochondria in humans and quadrupedal animals. AB - The relationship of VO2max to muscle oxidative capacity (estimated morphometrically as the volume of mitochondria of the entire musculature) was analyzed by compiling data on 8 species of mammals varying widely in VO2max. Over a five-fold range of weight-specific VO2max, a linear relationship between VO2max and muscle mitochondria was found. As an exception, humans seem to have 'excess' mitochondrial volume for their VO2max. However, the rate at which mitochondria operate in vivo at VO2max is found to be very similar for humans and quadrupedal animals. A larger total mitochondrial volume thus accounts for the well known finding that humans are capable of reaching VO2max with a subset of their body musculature. In quadrupedal animals the oxygen delivery system is geared to supply the entire musculature while in humans, possibly as a consequence of the upright posture, the cardiovascular system is designed to supply only a fraction of the total muscle oxidative capacity at VO2max. PMID- 2218096 TI - Operation Everest II: cardiac filling pressures during cycle exercise at sea level. AB - To examine the relationship between cardiac filling pressures during exercise in man and oxygen transport, we examined sea level data from Operation Everest II. The results showed that, (1) both right atrial and wedge pressures rose with heavy exercise in normal man, (2) the magnitude of the rise in these filling pressures related both to stroke volume and maximum exercise capacity, (3) wedge pressure was tightly coupled to right atrial pressure, with each mm Hg increase in right atrial pressure resulting in a 1.4 mm Hg increase in wedge pressure, and (4) very high wedge pressures occurred (in some subjects greater than 30 mm Hg), which contributed to an elevation of pulmonary arterial pressure. Thus direct measurements indicate right heart filling pressure increases with exertion in normal man, probably providing the necessary right heart output to fill the left heart. We speculated that the high cardiac filling pressures might be needed to maintain oxygen transport during heavy exercise, and that such pressures could contribute both to elevated pulmonary arterial pressure and to increased filtration of water into the lung. PMID- 2218097 TI - Comparative aspects of maximal oxygen consumption. AB - The respiratory system, that is the set of compartments interposed between the cells and the environment, is best studied among mammals. Across the compartments there exist net fluxes of O2 and CO2, the intensities of which depend on the animal's size. In steady state, at rest, the relation between O2 flux and body size has the form of an allometric equation in which the O2 consumption, MO2, is proportional to body mass with an exponent or scaling factor of about 0.75 (Brody, 1945; Kleiber, 1961). The principal experimental methods to force animals to maximal MO2 are cold exposure and exercise. According to the concepts of physiological time, strenuous exercise to reach maximal MO2 should be shorter in small animals than in large ones. The scaling factor for maximal MO2 seems to be higher than standard conditions; in other terms, large exercising mammals may increase their maximal MO2 more than small animals. The comparative approach of maximal MO2 is a powerful tool for finding where in the respiratory system the strictures or bottlenecks are which may limit O2 consumption. According to the ambient or organismal conditions (pressure, temperature, posture, nutrition), the site of the stricture may vary. As far as is known, the O2 consumption of the whole human body, in standard conditions as well as in maximal activity, and for a given mass, is such that, compared to other mammals, the human exhibits no species-specific characteristics. PMID- 2218098 TI - Effects of normobaric and hypobaric hypoxia on ventilation and arterial blood gases in ducks. AB - We measured ventilation (V1) and arterial blood gases in awake Pekin ducks exposed to normoxia at sea level, normobaric hypoxia achieved by lowering FIO2 at normal barometric pressure (NORMO), and hypobaric hypoxia achieved with a low pressure chamber and 21% O2 (HYPO). Average normoxic values were: V1 = 0.46 L . (kg.min)-1, PaO2 = 99.7 Torr, PaCO2 = 30.1 Torr. At PIO2 = 90 Torr, NORMO and HYPO measurements were not significantly different (P greater than 0.05). At PO2 = 46 Torr, NORMO V1 was less than HYPO V1 but blood gases were not significantly different: VI = 1.00 vs 1.45 L . (kg.min)-1; PaO2 = 31.3 vs 33.0 Torr; PaCO2 = 11.5 vs 10.6 Torr. Although both tidal volume (VT) and respiratory frequency (fR) were greater in HYPO, similar blood gases with NORMO and HYPO suggest similar parabronchial ventilation. The results suggest increased physiologic dead space, caused by reduced efficacy of aerodynamic valving, with reduced gas density in hypobaria. PMID- 2218099 TI - The critical concentration of surfactant in fetal lung liquid at birth. AB - Various doses (0-4.8 mg) of porcine surfactant were administered into the airways of immature newborn rabbits delivered at a gestational age of 26 days and 17-23 h. When the estimated concentration of exogenous surfactant in the lung liquid was less than or equal to 0.75 mg/ml (dose 0.6 mg), an average tidal volume of no more than a 3.0 ml/kg was obtained by mechanical ventilation with a peak insufflation pressure of 25 cm H2O, but when the estimated concentration was increased to 1.5 mg/ml (dose 1.2 mg), an average tidal volume of 17.7 ml/kg was attained, and the survival rate during a 30-min period of artificial ventilation improved significantly, from 14% to 53%. Even larger average tidal volumes, about 25 ml/kg, were recorded in animals with estimated surfactant concentrations of 3 and 6 mg/ml (doses 2.4 and 4.8 mg, respectively). In vitro observations revealed that the surface adsorption time of the surfactant suspension decreased non linearly from 20 to 1 sec when the concentration was increased from 1 to 3 mg/ml. The minimum surface tension during cyclic film compression also decreased non linearly from greater than 15 to less than 3 mN/m with the same increments in concentration. This led us to conclude that, under the present experimental conditions, the critical concentration of surfactant in fetal lung liquid at birth (about 3 mg/ml) is close to the concentration required in vitro for rapid adsorption and optimal dynamic surface properties. PMID- 2218100 TI - Influence of lung volume and rib cage configuration on transdiaphragmatic pressure during phrenic nerve stimulation in man. AB - Transdiaphragmatic pressure was recorded during bilateral supramaximal percutaneous phrenic nerve stimulation at 1 Hz (twitch Pdi) to investigate the effect of lung volume and rib cage configuration on diaphragm contractility in man. Stimulations were performed in 5 normal supine subjects at resting end expiration (FRC) and at lung volumes above and below FRC, during relaxation against a closed airway and during isovolume manoeuvres. Twitch Pdi at FRC was 24.4 cm H2O. At lung volumes above FRC, twitch Pdi decreased by 7.04 +/- 3.2 cm H2O per litre of volume change. At lung volumes below FRC, twitch Pdi increased by 12.4 +/- 8.6 cm H2O per litre of volume change. When the diaphragm was lengthened during an isovolume manoeuvre at FRC, twitch Pdi increased. A similar relationship between lung volume and twitch Pdi was obtained during stimulations performed with abdominal binding. These results demonstrate that the pressure developed by the diaphragm during phrenic nerve stimulation is significantly affected both by increases and decreases in lung volume and by the rib cage configuration at which stimulation is performed. PMID- 2218101 TI - Cardiopulmonary responses to HCl infusion are mediated by thromboxane A2 but not by serotonin. AB - Intravenous infusion of HCl has been shown to elicit the release of thromboxane A2 (TxA2) which alters blood pressure and breathing independent of reductions in circulating blood pH. The present experiments were designed to determine if the release of serotonin (5-HT) in the anesthetized cat contributed to cardiorespiratory responses during acid infusion and, furthermore to define the source of TxA2, viz. blood or other tissues. To infuse HCl into the bloodstream without reducing circulating blood pH (= neutral acid-base infusion), an extracorporeal arteriovenous shunt (20 ml/min) between the femoral artery and femoral vein was installed. Into this loop, acid (0.25 M HCl), and approximately 10 cm downstream, base (0.25 M NaOH) could be infused whereby blood pH could be locally reduced in the blood within the loop. This procedure was performed in three groups of cats: one group which received no drugs, a second group that was pretreated with indomethacin (2.5 mg/kg) and a third group that received the 5 HT2 receptor antagonist, ketanserin (0.75 mg/kg), prior to the infusion. During neutral acid-base infusion in the nontreated animals, right ventricular blood pressure (PRV) increased and systemic arterial blood pressure (Pa) decreased. Respiratory frequency was increased, but total ventilation was not elevated because of a concomitant fall in tidal volume (VT). The response was transient and could not be evoked with repetitive infusions of HCl and NaOH. These responses were significantly attenuated in the indomethacin-treated animals, but persisted in the cats pretreated with ketanserin. In addition, TxB2, the stable degradation metabolite of TxA2, was elevated during the acid/base infusion, but there were no measurable changes in plasma 5-HT concentration. The source of TxA2 was likely to be the blood since TxB2 was increased in plasma when acid and base were added to blood in vitro. We conclude from these experiments that transient cardiorespiratory responses to HCl infusion are mediated by the release of TxA2 from the blood and do not involve serotonin. PMID- 2218102 TI - Effect of adenosine on chemosensory activity of the cat aortic body. AB - Adenosine, which is released during hypoxia, increases carotid chemoreceptor discharge. It is not known if adenosine also may stimulate the aortic chemoreceptors. The purpose of this study was to investigate if adenosine also can stimulate aortic chemoreceptors. The effect of adenosine (0.01, 0.1 and 1.0 mumol/kg) on aortic chemoreceptor discharge was studied in seven anesthetized, paralyzed and artificially ventilated adult cats. Intra-aortic injections of adenosine produced an increase in chemoreceptor discharge, which reached its peak between 10 and 20 s. The chemoreceptor augmentation increased with higher doses of adenosine. Adenosine also caused a fall in blood pressure. The increase of chemoreceptor discharge was not related to fall in arterial blood pressure. Since adenosine is released during hypoxia, it is suggested that part of the cardiovascular changes induced by hypoxia is due to stimulation of aortic chemoreceptors by adenosine. PMID- 2218103 TI - Oxygenation properties of the two co-occurring hemoglobins of the tube worm Riftia pachyptila. AB - Riftia pachyptila vascular blood and coelomic fluid contain two hemoglobin molecules that differ in their distribution and physical properties. The present study of the two isolated hemoglobins shows that both have an extremely high affinity for oxygen, but differ in their oxygenation characteristics. FI, the larger molecular weight (Mr) fraction (1,700,000), has a lower oxygen affinity, a well defined pH Bohr effect, and high cooperativity of oxygen binding. FII, the lower Mr fraction (400,000) has a higher oxygen affinity, no pH Bohr effect, and reduced cooperativity of oxygen binding. Both hemoglobins show marked effects of temperature on oxygen binding, and no effect of heme concentration or the presence of sulfide on oxygen affinity. The differences in the oxygenation properties and distribution of the two hemoglobins in the body fluids of Riftia pachyptila may allow them to play different roles in oxygen transport and storage for the animal which lives in the variable environment of the hydrothermal vents. PMID- 2218104 TI - Solute-coupled liquid absorption from the pleural space. AB - The occurrence of a solute-coupled absorption of liquid from the pleural space was studied by measuring in anesthetized rabbits the volume of liquid of the right pleural space 1 h after injecting into it 2 ml of Ringer solution or of Ringer with an inhibitor of a Na(+)-Cl- coupled transport or of the Na+/K+ pump. Volume collected after Ringer was 1.56 +/- 0.08 ml. Initial volume being 2.2 ml, net absorption rate was 0.64 ml/h. Volume collected after disulfonic stilbene (0.1 mM) or bumetanide (0.1 mM) was 2.01 +/- 0.06 and 2.01 +/- 0.05 ml, respectively; net absorption rate was reduced to 0.19 ml/h. This suggests the occurrence of Na(+)-Cl- coupled transports. Volume collected after ouabain (0.5 mM) was 2.08 +/- 0.08 ml; net absorption rate was reduced to 0.12 ml/h. This suggests the occurrence of the Na+/K+ pump. The marked reduction in the hydrothorax absorption produced by the inhibitors shows the occurrence of a solute-coupled liquid absorption from the pleural space. Liquid absorbed through the visceral pleura by the solute-coupled transport should be removed by the Starling forces of pulmonary capillaries. Solute-coupled absorption of liquid through the parietal pleura should oppose the filtration caused by the Starling forces. PMID- 2218105 TI - Active Na+ transport across Xenopus lung alveolar epithelium. AB - Bioelectric properties and unidirectional ion fluxes of alveolar epithelium were studied by utilizing excised Xenopus lungs mounted in the flux chamber under short-circuited conditions. Results show that the alveolar epithelium generates a potential difference (PD) of 8 mV (lumen negative) with a tissue resistance (Rt) of 1000 ohm.cm2. The short-circuit current (Isc) is inhibitable by 80% with alveolar amiloride. Alveolar or pleural exposure of ouabain slowly decreases Isc to zero. Rt is slightly increased by either agent. Control tissues exhibit a greater unidirectional 22Na+ flux in the alveolar to pleural (A----P) direction than in the opposite (P----A) direction, indicating a net removal of Na+ from the alveolar fluid. Amiloride and ouabain both decrease the A----P Na+ flux to the level of the P----A flux, thereby abolishing net Na+ absorption. In contrast, unidirectional 36Cl fluxes are not different in either direction. Neither amiloride nor ouabain affected these 36Cl fluxes and tissue resistance appreciably, indicating that Cl- passively permeates the alveolar epithelium. PMID- 2218106 TI - Effect of surfactant on bioelectric properties of canine tracheal epithelium. AB - The functional significance of pulmonary surfactant in the airways is not well known and the effects of surfactant on bioelectrical properties of airway epithelium have not been investigated. In the present study, we examined the effect of synthetic surfactant (TR-14) or calf lung surfactant extract (surfactant TA) on transepithelial potential difference (PD) and short circuit current (SCC) in canine trachea. The conductance (G) was calculated as the ratio of SCC per open-circuited PD. The posterior membrane without muscular layer from canine trachea was mounted in an Ussing-type chamber, bathed with Krebs-Ringer buffer solution at 37 degrees C and gassed with 95% O2-5% CO2, pH 7.4. Treatment with mucosal surfactant produced an increase in both PD and SCC in a dose dependent fashion. PD and SCC reached 132% and 124% of before control at 0.25 mg/ml after the addition of each surfactant respectively, whereas G remained unchanged. Both ouabain and furosemide abolished surfactant-evoked increases in PD and SCC, whereas amiloride did not alter the surfactant-evoked increases. No significant differences in the effect on bioelectric parameters were observed between TR-14 and surfactant TA. These findings suggest that lung surfactant affects bioelectrical properties and changes ion transport (Cl- secretion) across airway epithelium, probably through the activity of ion pumps in the cellular membrane. PMID- 2218107 TI - Ischemia potentiates the reflex bronchodilation evoked by static muscular contraction in dogs. AB - In eleven anesthetized dogs, we found that static contraction of hindlimb muscles that were freely perfused decreased total lung resistance by 0.7 +/- 0.1 cm H2O.L 1.sec, whereas static contraction of the same muscles rendered ischemic decreased total lung resistance by 1.5 +/- 0.4 cm H2O.L-1.sec (P less than 0.025). In ten other dogs, we found that static contraction of freely perfused hindlimb muscles decreased total lung resistance by 0.9 +/- 0.2 cm H2O.L-1.sec, whereas dynamic contraction of the same freely perfused muscles decreased total lung resistance by 1.1 +/- 0.3 cm H2O.L-1.sec. The difference in the magnitudes of the bronchodilator responses to the two modes of contraction was not significant (P greater than 0.05). We conclude that a mismatch between blood supply and demand in working skeletal muscle increases the reflex bronchodilator response to static contraction. We also conclude that dynamic contraction evokes a reflex bronchodilation equivalent to that evoked by static contraction provided that the tension produced by the two modes of contraction are equal. PMID- 2218108 TI - Vasodilators do not abolish pulmonary vascular critical closing pressure. AB - To examine whether the critical closing pressure (Pcrit) of the pulmonary vasculature is dependent upon vasomotor tone, we measured Pcrit in six dog lobes before and after the administration of vasodilators. We evaluated the pressure flow (P-Q) relationship in zone 2 flow conditions in situ perfused dog lobe (control period). We calculated Pcrit as the mean extrapolated zero-flow pressure intercepts for the P-Q relationship. We also used arterial and venous occlusions under zone 3 conditions to partition pulmonary vascular resistance into arterial, middle and venous segment resistances. We then repeated all measurements following administration of papaverine (150 micrograms/ml) and sodium nitroprusside (200 micrograms/min) into the venous reservoir (vasodilator period). Resistance in all three vascular segments was significantly reduced during vasodilator conditions. Pcrit decreased from 3.68 +/- 0.76 cm H2O to 2.53 +/- 0.92 cm H2O during control and vasodilator periods respectively (P less than 0.05). The slopes of the P-Q relationships were similar during both conditions. Our data support a model in which vasomotor tone normally sets Pcrit but in which the pulmonary vasculature can exhibit the phenomenon of critical closure even with vasomotor tone pharmacologically ablated. PMID- 2218109 TI - Effect on breathing of raising end-expiratory lung volume in sleeping laryngectomized man. AB - In animals, tonic vagal activity from lung receptors provides a means by which changes in end-expiratory lung volume can influence respiratory timing. We wished to examine whether increasing the end-expiratory lung volume within the tidal volume range had a similar effect in man. In order to minimize behavioral influences on breathing, the study was performed in subjects during deep non rapid eye movement sleep. Five laryngectomized subjects were chosen for the study since their permanent tracheal stomata allow simple, airtight connection to respiratory apparatus and avoided problems with glottic closure. During EEG documented sleep, end-expiratory volume was increased by up to 350 ml with the addition of expiratory threshold loads of 1 to 10 cm H2O. End-expiratory volume increased linearly with expiratory pressure. Inspiratory and expiratory times (TI and TE) were not affected by increases in end-expiratory volume. Tidal volume (VT) was decreased such that end-inspiratory volume remained unchanged. The decrease in VT may result from a reduction in inspiratory muscle efficiency at a higher lung volume. The results of the study provide no evidence that tonic vagal afferent information from the lungs is important in controlling respiratory rhythm within the tidal volume range in man when behavioral control of breathing is minimized. PMID- 2218110 TI - [Post-traumatic infections of the frontal sinus]. AB - Post-traumatic infectious complications of the frontal sinus occur more frequently after multiple fractures than after isolated fractures. The greatest frequency is found with open traumas of the sinus, due to the presence of foreign bodies and to bone and mucosal destruction. Such infectious complications are curatively treated both medically and surgically, to eliminate the bony and mucosal infection and to restore the normal physiology of the frontal sinus. Stress is laid on the preventive treatment, especially on the quality of the initial surgical treatment, either by restoring the sinus with gauging of the nasal-frontal canals, or by eliminating the sinusal function by a canalization which appears preferable to exclusion by obliteration. PMID- 2218111 TI - Nasal mucociliary function during the menstrual cycle in healthy women. AB - Nasal mucociliary transport time was studied in nine healthy women over the menstrual cycle using the vegetable charcoal powder technique. Three measurements were made at different points of the cycle: during the early follicular phase, periovulatory phase and luteal phase. The mean transport times were 10.1 +/- 3.50, 5.1 +/- 2.08 and 7.5 +/- 3.28 minutes, respectively. Transit was significantly accelerated during the periovulatory phase (p less than 0.01), when the seric estrogens are at their highest level. PMID- 2218112 TI - [The value of cellulo-adenectomy in the treatment of pharyngolaryngeal cancers without clinical adenopathy]. AB - The term cellulo-adenectomy involves dissection of all the neck jugulo-carotid lymph nodes below the digastric muscle and above the omo-hyoid muscle. From the study of 133 cases treated by primary surgery, it can be said that this technique is essentially diagnosis to verify the actual integrity of the jugulo-carotid lymph trunk in patients who are clinically NO and who present a lymphophile ENT tumour. Such a technique necessitates a macroscopic lymph examination with an extemporaneous anatomical and pathological examination. Subsequent therapy depends on the result; for N+ patients, further surgery and/or irradiation, irrespective of the site; for a confirmed N- patient, additional therapy depending on the site of the tumour. Our experience has shown that this approach is safe and enables the treatment of the lymph glands to be better adapted to the reality of the neoplastic invasion. PMID- 2218113 TI - [Primary and recovery transmaxillar buccopharyngectomy in buccopharyngeal cancers]. AB - From january 1976 to december 1986, 78 patients were treated surgically for squamous cell carcinoma of the lateral buccopharyngeal junction without chemotherapy at first. 36 patients were treated by primary surgery with post operative radiotherapy and 31 patients were treated by recovery surgery. Post operative course was uncomplicated in 41% of cases (39% in primary surgery, 43% in recovery surgery); in 14% of cases serious local complications were observed (11% in primary surgery, 17% in recovery surgery). Carcinological failures appeared in 46% of cases in primary surgery and in 70% of cases in recovery surgery. Three years and five years actuarial survival rate were 45% and 39% respectively in recovery surgery. Prognostic factors are studied: resection quality, histological metastasis in lymph nodes. The authors emphasize on the best control of the big tumors in primary surgery and on the best results with small ulcerated infiltrant carcinoma. PMID- 2218114 TI - [Analysis of prognostic factors in cervicofacial carcinology using the Cox model. An example of piriform sinus cancer]. AB - Analysis of prognosis factors was performed on a surgical series of 34 of piriform sinus cancer, based on the use of a multivariate study according to the Cox model. The presentation is essentially didactic emphasizing the main points: how to collect data, what data to collect, and what judgment criterion to use. The authors detail the interpretation to be drawn from the analysis results using Cox model. PMID- 2218115 TI - Pupillary pharmacologic test in Meniere's disease: a useful method for routine diagnosis. AB - The role of the parasympathetic system in Meniere's disease was investigated by a pupillary pharmacologic test (methacholine test), using a computed infrared pupillograph. The test was performed in Meniere's disease (16 cases), other vertiginous disorders (23 cases) and normal subjects (10 cases). The results confirmed the presence, during the attack stage of Meniere's disease in 75% of cases, of an abnormal sensitivity of the iris musculature to methacholine, prevalent on the affected side, and an increasing pupillary asymmetry. These features were found in 17% of the patients with other vertiginous disorders and in none of the control subjects. The parasympathetic dysfunction is interpreted as a supersensitivity of central origin and seems directly related to the disease. It is proposed that the methacholine test acts as a complement to the glycerol test in the diagnosis of Meniere's disease. PMID- 2218116 TI - [Functional study of vestibular receptors by combined electric and rotatory stimulations]. AB - After a brief review of the anatomical and functional characteristic of the inner ear, emphasizing audio-vestibular relationships, a direct method for recording peripheral vestibular potentials, the Electrovestibulogram (EGV) is described and compared with the techniques Electronystagmographic. Stimulating electrodes were implanted in the round window and vertex of a group of guinea-pigs, with recording electrodes near the internal acoustic meatus. A permanent electric stimulation was combined with an intermittent vestibular stimulation (horizontal angular acceleration) to derive afterfact-free vestibular specific responses. The characteristics of the EVG responses were analyzed and compared with the data in the literature concerning the responses of single fibres, to validate the technique. The diagnostic value of EGV is discussed. PMID- 2218117 TI - [Dynamic posturography in normal subjects]. AB - The relative lack of data on the dynamic posturography led us to start a study in order to give our contributions to the standardization of M1, M2, M3, response parameters in normal subjects. Our research was carried out on 35 normal subjects aged 21 to 50. All of them were standing in Romberg's position on a Tonnies model board in a normally lit and ventilated room. We performed two tests: the first one open-eyed staring at no point, the second, 5 minutes later, closed-eyed. The EMG signals were obtained by surface electrodes on triceps sural and front tibial muscles. The EMG recording was determined by a "tilt" movement of the board at a steady speed of 50 per sec. and 4 wide. We use a XT 286 IBM computer with "T POST" software for checking and testing the data. Our results showed a significant variation in the value of the duration parameter in open-eyed and closed-eyed tests. Latency and area values were inferior to those obtained by other authors, except for Diener and Dichgans (3) whose results differ in latency value only. PMID- 2218118 TI - [Sinus infection and diving (a case of cerebral empyema)]. AB - Intracranial complications following swimming or diving accidents are exceptional. A recent observation of a cerebral empyema in a 15-year old boy, with neurological sequellae was an opportunity the clarify the issue. Apart from the rapidity of the neurological signs, two points drew our attention: bacteriology, with a predominance of anaerobic germs; and the problem of therapy, both for the timing of neurosurgery and for the role of anticoagulants in venous thrombosis. PMID- 2218119 TI - [A case history of lateral cervical tumor]. AB - The authors report on the observation of a voluminous aneurysm of the common carotid that had developed over 20 years in an 88-years old female patient. This was treated surgically by a Gore-Tex carotid graft with perfectly straightforward operative sequellae. With respect to this case, the author briefly review the semiology and diagnosis of aneurysms of the neck. PMID- 2218120 TI - [Tuberculosis of the cavum, report of two cases]. AB - The authors report two cases of nasopharynx tuberculosis. This location is rare or misestimated. The sarcoidosis, the Wegener's granulomatis can be discussed. The diagnosis confirmation is based on the histologic features as a caseous necrosis in a langhans reaction cells or as the presence of mycobacterium tuberculosis at a Ziehl-Nielson coloration. The authors insist on the interest of a systematic biopsy of the nasopharynx at the presence of a nasopharynx lesion or a primitive cervical lymph-nodes. A bacteriologic investigation have to be done before the beginning of the specific treatment. PMID- 2218121 TI - Anatomy of the larynx, study of the anterior branch of the recurrent laryngeal nerve. AB - These studies are based upon 60 dissections of the recurrent laryngeal nerve. The authors describe the branches destined for the intrinsic musculature of the larynx. This study is a working approach for the operations of selective laryngeal reinnervation in man. PMID- 2218122 TI - Surgical anatomy of the superior laryngeal nerve. AB - The authors report on their anatomic findings in 42 surgical dissections of the superior laryngeal nerve. Better knowledge of this anatomy should enable a more conservative cervical surgery and help in attempts at nervous rehabilitation of laryngeal paralysis. PMID- 2218123 TI - [Systematization and histomorphometry of human laryngeal nerves]. AB - Laryngeal nerves were dissected from 100 fresh subjects in order to compare right and left superior and inferior laryngeal nerves. The origin and the distribution of the vascularization was studied. The structure of these nerves was precised through an histomorphometric approach (distribution number of myelinated fibers per mm2, diameter of myelinated fibers). A cartographic study of the laryngeal nerves confirmed the structure of this innervation. The main conclusion of this study is the importance of the plexis structure of the laryngeal innervation and the variations of the nerve fibers diameter as a function of the length of the fiber. PMID- 2218124 TI - [Otospongiosis: different surgical technics, identical results. Why?]. AB - Both platinectomy and platinotomy are currently used to treat otosclerosis surgically. Though the techniques are different from one another, especially by the new area ratio between tympanic membrane and stapes foot-plate, the results are similar. It should be clear that the simple "piston model" of the tympanic ossicular system cannot explain this results. If, for the seesaw mechanical view, a vibratory molecular system conducting acoustic energy is substituted, a pertinent explanation can be given for this result. Thus, understanding of the pattern motion of the tympanic ossicular system has to change drastically. PMID- 2218125 TI - [Pulse oximetry: an indicator for the closure of a tracheostome after lateral fixation of the vocal cords (cordopexy)]. AB - The aim of the study was to establish an objective method to predict proper breathing after the closure of the tracheostomy in patients operated upon for laryngeal diplegia by lateral cordopexy. The method is non-invasive, quantitative and independent of the patient. The study covers 18 patients in whom the closure was performed after fixation of the vocal in whom it was performed prior to the operation. The arterial oxygen saturation was measured during closure using a beat-to-beat pulse oximeter and compared with the open tracheostomy, with the closed tracheostomy at rest and under stress, and finally with the closed tracheostomy in the recovery phase. The effort was continued for 5 minutes or until the patient complained of shortness of breath (3 patients). Initially the O2 saturation in these patients did not drop below 90%, but respiratory dependent saturation variations were noted. During the recovery phase, the saturation fell below 90%. The subjective declaration of "asphyxia" always preceded the variations in the O2 saturation. From this, and from the O2 saturation curves, we conclude that the cause for the reopening of the tracheostomy comes more from a circulatory problem that from hypoxemia. PMID- 2218128 TI - [Ophthalmological complications in ORL and maxillofacial surgery]. AB - E.N.T. and maxillo-facial surgery may sometimes cause dramatic eye damage. Following a brief summary of the eye's anatomy and its surrounding parts, the most frequent surgical acts which may cause orbital complications are described. Perfect knowledge of the eye and its surrounding parts enable us to offset the dramatic changes due to the pathology. PMID- 2218126 TI - [Use of the Musco NT3 tympanic isopressor in tubal dysfunction. Apropos of 30 cases]. AB - We have studied the tolerance and efficacy of tubal insufflations with the MUSCO NT3 isopressor (Bexen) in a sample of 30 patients suffering from chronic tubal pathology. The apparatus was modified for use with an Itar Catheter. We recorded a favourable evolution of serous otitis (9 cases of normalization), with little modification of the retraction pockets. The paraclinical study revealed a major and significant overall, audiometric and tympanometric improvement. PMID- 2218127 TI - [Management of open and closed cavities in otology]. AB - Surgery of chronic otitis follows a few basic principles, some of which are long standing but still topical. In the majority of cases, opening of the cavities of the middle ear uses one of the following two techniques: the open technique (radical mastoidectomy), or the closed technique (transmastoid approach or canal up technique). Whatever the technique used, a readjustment of the cavity is often indispensable to avoid any recurrence of the pathology (cholesteatoma) or the appearance of a new pathology (chronic otorrhea) and facilitates a functional step if required. Open techniques must therefore always follow the rule of the ratio V/S (where V = the volume of circulating air coming from outside, and S = the surface area of the skin of the cavity). This ratio is specific to each individual. The readjustment must enable either an increase of V (meatoconchaplasty) or a decrease of S (reconstruction of the posterior auditory canal, obliteration of the cavity), or a combination of the two. Closed techniques must also be adjusted to avoid any retraction towards the posterior or upper cavities. Depending on the clinical background and on the aggressivity of the pathology, the posterior tympanotomy can be closed, and the attic and aditus cavities of the middle ear separated by a bony fragment leaving the protympanum open upwards to enable normal ventilation towards the attic, the aditus and the antrum, or much more rarely, these cavities can be completely closed. PMID- 2218129 TI - [Focal infection? Did you say focal infection ... focal infection and uveitis]. AB - A chronic seat of infection more often than not situated in the E.N.T. area is responsible for remote pathological symptoms commonly called focal infection. The eye may be a target organ, where focal infection appears in the form of a uveitis. Four clinical observations are reported as demonstration. The transmission mechanism operates through an immune phenomenon from bacterial antigens which engender reactions of hypersensitivity. The E.N.T. specialist must be aware of these symptoms and seek a pharyngeal, sinusal or latent buccodental infection. PMID- 2218130 TI - [Oculo-orbital injuries caused by firearms. Clinical and ballistic study of 3 cases]. AB - For 3 cases, the authors made a clinical and ballistic analysis of the penetration of war projectiles inside the eye and the orbit. They emphasize the seriousness of the injuries, the multiplicity of the operations, the need for participation of different specialists and lastly, the almost-inescapable loss of sight. PMID- 2218131 TI - [Total ethmoidectomy using the mixed rhinoneurosurgical approach for malignant tumors of the anterior skull base. 14 years' experience. 62 cases]. AB - Based on 62 cases, the authors report on 14 years of experience of total ethmoidectomies through a mixed rhinological and neurosurgical approach. Following a survey of the main points of the surgical technique, they emphasize the major evolution undergone, on the one hand, by the preoperative topographic diagnostic possibilities thanks to progress in imaging, and, on the other hand, the operative technique itself. The optimization of the reconstruction time for the base of the skull seems to provide a substantial advantage by reducing morbidity and operative mortality. The use of the epicranial flaps and to a lesser degree, cryo-stored bone allografts are the major stages. Prognostically speaking, the mixed approach offers a clear improvement in the 5-year survival rate of adenocarcinomas (80%), and olfactory placode tumors. However, the prognosis for epidermoid carcinomas continues to be poor (35% at 5 years) due to the frequency of local recurrences and visceral metastases. PMID- 2218132 TI - Acoustic neuroma: anatomo-clinical correlations in the posterior wall of the temporal bone. AB - A morphometric study of relationships among cranial nerves V-VI-VII-VIII-IX-X-XI XII and the posterior wall of the temporal bone was done in 58 specimens. Large variations occurred in measurements. Results were correlated to a clinical study of 30 patients undergoing surgery for removal of acoustic neuromas. No correlations could be found between size and shape of external auditory meatus (E.A.M.) and internal auditory meatus (I.A.M.) in the same temporal bone. Mean distances from the point where cranial nerves enter the temporal bone to the I.A.M. were: trigeminium nerve, 7.8 mm; abducent n., 15.2 mm; hypoglossus n., 21.4 mm; and glossopharyngeal n., 5.3 mm. Although the jugular foramina is the closest structure to the I.A.M., cranial nerves IX-X-XI were never clinically impaired in all 30 patients studied here. Clinically diagnosed trigeminium nerve impairment occurred more often than facial paralysis (33.3% against 20% of patients). It seems that motor fibers are more resistant to tumoral compression and distension. PMID- 2218133 TI - [Irradiation of neurinoma. Why? How? First results]. AB - The treatment of acoustic neurinomas is above all surgical. Five situations lead us to opt for radiotherapy: the patient's poor general condition, tumoral bilaterality with a single ear, tumoral remnants, evolutive recurrences or relapses and lastly, tumoral hypervascularization (pre-operative radiotherapy). Therefore, 19 patients were treated between 1986 and 1988 by linear accelerator photons or cobalt, at doses of 50 to 60 Gy (1.8 Gy per session). Indubitable effectiveness was observed on the tumoral volume in the form of stabilization or regression in 14 cases. The evolution of hearing after treatment is not as favorable: out of 8 patients with good hearing on the irradiated side, 3 maintained identical thresholds, but 5 secondarily developed total deafness. The therapeutic protocol change will perhaps allow for improvement in hearing preservation. PMID- 2218134 TI - [Tuberculosis of the upper digestive and respiratory tract]. AB - Based on seventeen cases of upper digestive and respiratory tract tuberculosis, the authors review the different localizations of the disease. The mean age of the patients is 34 years old. The diagnostic is based on bacteriological and especially histological examination. The prognostic of the affection is excellent if tuberculosis chemotherapy is used for a minimum of 9 months. PMID- 2218135 TI - [Naso-orbito-cerebral mucormycosis. A more & more common disease]. AB - A typical case of naso-orbital-cerebral mucormycosis is described. This rare but serious disease mainly occurs in fragile patients, notably diabetics or those undergoing an immunosuppressant treatment. The cases recorded are therefore increasingly frequent. Mucorales, normally saprophytic, germinate in the nasal cavities due to an infection and then colonize the sinuses, the orbit, followed by the meninges. The diagnosis must be made before meningeal impairment when faced with a peri-orbital edema, the beginning of exophtalmy or oculomotor paralysis in high-risk patients with sinusal opacity. The diagnosis is based on the histology and the mucology which must be directed by the clinician: indeed, the histology of the naso-sinusal mucosa samples must be performed using special stains. The mycological samples must also be taken from special environments. Once the diagnosis is confirmed, the required treatment with high doses of intravenous Amphotericine B must be administered immediately, otherwise the evolution is fatal. PMID- 2218136 TI - [Isolated sphenoidal aspergillosis presenting as an optic neuropathy]. AB - Aspergillosis fixation in the sphenoidal sinus is an exceptional occurrence when isolated. The clinical feature is misleading and the diagnosis often difficult; local and regional complications are dreadful. The authors report a case, presenting as an optic neuropathy, and the literature data. PMID- 2218137 TI - [Isolated fractures of the medial orbital wall, surgical indications in 5 cases]. AB - Isolated fractures of the medial orbital wall are always blowout fractures. They are usually diagnosed when horizontal diplopia occurs (lateral movements of the globe and Lancaster test). If the medial rectus muscle is encapsulated (forced ductions and CT-scan), the area of restriction has to be explored surgically. PMID- 2218138 TI - [Pneumatocele caused by ballistic injury of the anterior stage of the skull base, a case report]. AB - The authors present a case of intracerebral expansive pneumatocele following a ethmoido-sphenoidal fracture by a bullet. The case presented is exceptional, as the bullet went through the brain case without injuring the neurological structure. The patient is operated on through the low paralateronasal approach, by filling the ethmoid and the sphenoid with autologous bone material. This surgical treatment makes closure of the fistula and disappearance of the pneumatocele possible, however, not enough time has gone by for making other judgments. This approach, which has a much lower morbidity rate than the approach of the anterior stage through craniectomy, is effective for fractures of the sphenoid and the posterior ethmoid. PMID- 2218139 TI - [Radiation-induced sarcoma, apropos of a case with cervical and intrapetrous development]. AB - The authors report on a case of fibrosarcoma of the secondary petrous part of the temporal bone following irradiation, eight years earlier, of a cerebellar astrocytoma. Based on a review of the literature, they recall the characteristic traits of these tumors: development in the field of irradiation, prolonged latency period, exact histology, rarity of cervico-cephalic locations. The treatment usually associates wide surgical exeresis and chemotherapy. The prognosis remains poor due to local recurrences and visceral metastases (20 to 60% at five years). PMID- 2218140 TI - [Efficacy of Cefsulodin in pyocyanic otologic infections, apropos of 55 cases]. AB - Our work consists of a comparative study of 4 therapeutic protocols for treatment of otological infection from the pyocyanic bacillus, and more specifically of 19 patients with a necrotizing malignant otitis, 24 patients with perichondritis and 12 patients suffering from a post-operative infection. The association of Cefsulodin (a 3rd generation Cephalosporin) and Gentamicin gave the best results. A major decrease of the time of treatment and a total absence of infectious complications were in fact recorded. The adjuvant therapies were duly observed for the 4 protocols, in particularly the surgical treatment and the treatment of the site (diabetes). PMID- 2218141 TI - [Role of the free forearm flap in reconstruction after total circular pharyngolaryngectomy. Review of the literature and a case report]. AB - Methods of surgical repair after total pharyngo-laryngectomy have considerably improved since the introduction of micro-surgical techniques. The use of free autografts for reconstruction of the pharynx is now preferred in most centers to the use of musculo-cutaneous flaps. The free forearm flaps appears to be particularly suitable for this type of repair. The authors report on their experience in performing this procedure with one of their patients. The results of this technique in major published series are then compared with those achieved with similar procedures employing free jejunal interposition grafts. PMID- 2218143 TI - [Treatment of subglottic stenoses using the Pearson's operation: apropos of 3 cases]. AB - Surgery of stenoses of the laryngo-tracheal junction is governed by the necessity of maintaining the support of the cricoid-arytenoid articulations and of preserving the recurrent nerves. Sub-total cricoid resection with conservation of the recurrent nerves, known as Pearson's operation, enables the treatment of fixed sub-glottic stenoses with mobile larynx. On the basis of three recent observations, the authors define the indications and the performance of this surgery. The respiratory and vocal results are considered satisfactory in these three cases. PMID- 2218142 TI - [Treatment of laryngotracheal stenoses in children]. AB - Over a period of 5 years, from 1984 to 1989, 35 children were treated surgically for a laryngo-tracheal stenosis, 27 by an external approach, 8 by endoscopy with the CO2 laser. Of the children, 25 (71%) were under 5 years old at the time of treatment and 77% of the stenoses (n = 27) corresponded to a post-intubation and/or tracheotomy acquired etiology. Based on the classification of stenoses according to the extent of the impairment of the aerial lumen, the authors stress the value of conservative treatment (endoscopy) in Stage I (less than 70%, n = 8), and of treatment using the external approach in Stage II (between 70% and 90%, n = 12), in Stage III (between 90% and 99%, n = 12) and Stage IV (complete obstruction, n = 3). The technique most widely used currently is laryngo tracheoplasty with the insertion of costal cartilage (n = 17). Analysis of the results shows that decannulation was successful in 85% of the cases. With respect to the management of stenoses in the new-born baby, the authors report on their recent experience with laryngo-trachoe-fissure in 6 cases as an alternative either to tracheotomy in difficult extubations, or to laryngo-tracheoplasty when the child's weight is particularly low. PMID- 2218144 TI - [Surgical anatomical study of the spinal nerve]. AB - 100 dissections performed in the Anatomy Laboratory have made it possible to clarify certain details relating to the cervical trajectory of the accessory nerve (traditionally called the 11th or spinal nerve), its relationship with the jugular vein, with the S.C.M. muscle, its position on the anterior and posterior edges of the S.C.M. and on the anterior edge of the trapezius muscle, and the frequency of its branching in the sub-clavicular fossa. PMID- 2218145 TI - Pathology of the uterine cervix. PMID- 2218146 TI - Squamous cell carcinoma of the uterine cervix--a review with emphasis on prognostic factors and unusual variants. AB - Although the incidence of squamous cell carcinoma of the cervix has declined in recent years, it remains the most common type of cervical cancer in our society. In this review, the salient pathologic features of squamous cell carcinoma are discussed. Early invasive, International Federation of Gynecology and Obstetrics (FIGO) stage la carcinoma has been a source of controversy in diagnosis and therapy for many years. Specific requirements must be met in order to make this diagnosis. Most importantly, the cervical conization specimen must be handled properly, so that the features of tumor dimensions, vascular involvement, and completeness of excision can be correctly evaluated. Important diagnostic and prognostic pathologic findings of early invasive carcinoma are discussed. The risk of lymph node metastasis in lesions with depths of invasion up to 3 mm is less than 1%. This risk increases significantly with deeper levels of invasion. In the area of frankly invasive squamous cell carcinoma of the cervix, certain pathologic features have been shown to be clinically relevant. These include the extent of local disease, cell type, and the presence of vascular or lymphatic invasion. Regarding cell type, it is critical to distinguish between poorly differentiated small cell squamous carcinoma and small cell undifferentiated carcinoma, as the prognosis for these tumors may differ. Finally, several rare but pathologically distinct variants of squamous cell carcinoma of the cervix are reviewed, with emphasis on differential histologic features. As they often have different natural histories than typical squamous cell carcinoma, correct diagnosis of these lesions is vital. PMID- 2218147 TI - Invasive adenocarcinoma and related tumors of the uterine cervix. AB - Adenocarcinomas and related tumors now account for approximately 15% of carcinomas of the uterine cervix. In this review, the features of these neoplasms are reviewed with emphasis on their microscopic features, differential diagnosis, and subtypes about which there is new information such as adenoma malignum, and villoglandular, mesonephric, adenoid basal, and adenoid cystic carcinomas. These tumors may cause considerable diagnostic difficulty, sometimes being difficult to distinguish from nonneoplastic glandular proliferations. Their correct identification has major prognostic implications. PMID- 2218148 TI - Variability of symphysis-fundus height measurements: an experimental study among general practitioners. AB - With the aim of evaluating the impact of supervised training during a postgraduate course in obstetrics and gynaecology, the variability of symphysis fundus (SF) height measurements was studied by a group of general practitioners (GPs), all of whom provided primary antenatal care. A nested analysis of variance was used. The SF height measurements of the group differed significantly from those of a senior obstetrician and the course training had no impact on the variability. Similar studies should evaluate measurement variability in the light of pregnancy outcome. PMID- 2218149 TI - Failure to keep appointments at a community health centre. Analysis of causes. AB - The scheduled appointment system in primary care clinics became popular recently in Israel. Failed appointments created a problem for the doctors, patients and the clinic in Netivot. During 11 months, 2.317 appointments were surveyed. The survey showed 36% of failed appointments, with a decrease to 28% one year later. Rates of failed appointments were 38% for the paediatric population, 35% for adults, and 34% for pensioners. Market days and holidays predisposed to more failed appointments, representing community customs. The presence of a chronic disease that needed follow up ensured a higher rate of attendance (76%), especially among the paediatric population (92% attendance rate). By contrast, a geriatric patient with an acute disease had difficulty attending the clinic (only 16% attending). 512 people (35% of the population) were responsible for the 827 failed appointments, and among them only 12% of the population accounted for 59% of the failed appointments. These findings have important implications in the planning of an appointment system in an urban health centre, and they strengthen the assumption that a small number of patients cause a large number of failed appointments. PMID- 2218151 TI - A retrospective study of respiratory tract infections among children in different forms of day care. AB - This retrospective study investigated the records from July 1985 to June 1986 of all medical visits due to acute respiratory tract infections (RTIs) in infants aged 1-3 years. The study, in a municipal district, included all visits to the district health centre as well as visits to the paediatric and ear, nose and throat departments of the nearby hospital. The study population consisted on 489 children, of whom 140 were cared for in day-care centres (DCC), 146 in family day care (FDC), while 203 did not receive any sort of municipally-supported day care (home care, HC). During the year studied, 223 children needed treatment by a doctor for acute RTI on altogether 499 occasions leading to the prescription of 325 courses of antibiotics. As regards RTIs as a whole and regarding those treated with antibiotics, the incidence density was greatest among the DCC children and lowest among the HC children, while the FDC children formed an intermediate group. PMID- 2218150 TI - Intervention against long-term use of hypnotics/sedatives in general practice. AB - The aim of the study was to evaluate the efficiency of different strategies of intervention to reduce prescription of hypnotics/sedatives in general practice. All 356 general practitioners in the county of Aarhus, Denmark, were divided in three groups. One group received personal information at meetings, another received written material about proper use of hypnotics/sedatives and information about their own prescription rate, and the third group constituted a control group. The prescription rate was recorded before and after the intervention. There was a general decline in the prescription rate recordings, but there were no significant differences between the intervention groups and the control group. PMID- 2218152 TI - Lower mortality of demented nursing home residents. A two-year survival study. AB - The mortality of 318 patients residing permanently in a nursing home was analyzed over two years in a retrospective study. Survival analysis showed that age was significantly associated with increased mortality, and dementia with decreased mortality. The results may to some extent explain the large percentage of demented patients in nursing homes, and provide some support for the hypothesis that demented patients accumulate in the nursing homes, partly due to inappropriate community services for these patients, leading to a relatively early institutionalization. PMID- 2218153 TI - A three-year training programme for primary health care physicians in Poland. AB - A three-year training programme was developed and implemented by the Medical Centre of Postgraduate Education in Poland with the aim of improving the knowledge and skills of primary health care physicians working in the State Health Services' community centres. The programme creates several learning and self-assessment opportunities with the general principle of not distracting a doctor from his daily duties in a community health centre for more than one day a month. Preliminary assessment of the programme revealed its positive impact on both the health services system and primary health care physicians themselves. It increased health authorities' activity in creating new learning opportunities and doctors' motivation to learn. Self-assessment made by the first group of trainees who completed the three-year programme (results obtained by means of a questionnaire) revealed substantial increase in professional competence resulting from the participation in the programme. PMID- 2218154 TI - The general practitioner and the HIV epidemic. PMID- 2218155 TI - On promises and premises in qualitative general practice research. PMID- 2218156 TI - Factors of importance for the use of PAP-SMEAR in a Danish county without systematic screening. AB - Do various General Practice factors influence the participation rate (PR) in the cytological investigation for preventing cancer of the cervix uteri in counties without systematized screening? This was studied in the county of Aarhus, Denmark, where there are no systematic cytological examinations (CE). We studied a random sample of 2023 women aged 27.5 years to 47.5 years. Essential differences in PR depended on various practice characteristics. Practices with the highest average use of CE services, as counted by the Regional Health Authorities, also had the best PR. The relative chance of being sufficiently examined was almost twice as great among patients in active practices compared with other practices. Furthermore, practices with at least one female practitioner and practices that wanted the introduction of systematic screening had a significantly higher PR. There was a slightly higher PR for patients in large practices. Type of practice, i.e. whether single or partnership, and the individual practitioner's attitude to the efficiency of the present opportunistic screening were not related to the PR. Finally, a slightly lower PR was found among patients in the city of Aarhus, whereas the PR in the major cities of the county as a whole did not differ from the coverage rate in the county in general. It is concluded that the Health Authorities' average figure for CE-use/1000 women in the individual practice is the most significant factor that determines the CE rate for any given patient. Variation in the PR in different practices is unacceptably large if all the women are to receive a uniform CE screening offer. PMID- 2218157 TI - HIV infections and AIDS in Danish general practice--the role of the GP in AIDS prevention. AB - The occurrence and geographical distribution of HIV infections and AIDS (HIV/AIDS) in Danish general practice were examined in a questionnaire study sent to a 10% random sample of the GPs. Response rate was 92%. In 1988, a total of 2969 patients were tested, median 10 patients per GP. GPs had 148 HIV-positive patients (66 in Greater Copenhagen) and 60 AIDS patients (27 in Greater Copenhagen). In Greater Copenhagen 37% of the GPs had neither HIV nor AIDS patients, vs. 71% in the rest of the country. Instruction in infection prophylaxis was usually initiated by the GPs, while HIV testing was mainly on the patient's initiative. 52% of GPs indicated a change in their routine, particularly with respect to sterilization of instruments and avoidance of direct contact with blood. An extrapolation of the results of this study indicates that about 1,500 of the estimated 2,000 HIV positive patients in Denmark are known by general practitioners. PMID- 2218158 TI - The diagnosis of bacteriuria during pregnancy. AB - Three diagnostic tests, Nitur, Urobact, and Uricult, were evaluated in the detection of bacteriuria in 865 pregnant women. As reference method agar culture was performed. Heavy growth (greater than 10(5) CFU/ml) of urinary tract bacteria was considered a true positive result and demonstrated in 58 (6.7%) of the women, 14 of whom had gram-negative rods. The sensitivity of the nitrite test was extremely low (0.13). The test gave negative results in eight of 17 specimens yielding heavy growth of Escherichia coli or Proteus mirabilis. Although the Urobact test was highly sensitive as regards gram-negative infection, it had an unacceptably low (0.27) predictive value in positive tests. The sensitivity of the Uricult test was low (0.35) in this study. The predictive value (0.50) of a positive test result may be acceptable, since just over half of the false positive results were explainable by moderate growth of urinary tract pathogens (10(4)-10(5) CFU/ml). It is argued that semi-quantitative urine culture may be preferable to the rapid diagnostic methods studied for the screening of bacteriuria in pregnant women. PMID- 2218160 TI - Doctors in a white coat--what do patients think and what do doctors do? AB - Patients and general practitioners in northern Norway were asked their opinion on the doctors' use of a white coat in the consultation. 51.9% of the patients wanted their doctor not to wear a white coat, whereas 11.7% of the doctors never wore one. 5.7% of the doctors' staff members never wore a white coat. The patients' preferences were to some extent related to their own doctors' use of a white coat, and there was a significant increase in the demand for a white coat with increasing age of the patients. PMID- 2218159 TI - Intravenous urography versus ultrasonography in evaluation of women with recurrent urinary tract infection. AB - Intravenous urography and ultrasonography were compared prospectively in 120 women with recurrent urinary tract infection. The median age was 44 years (range 15-85). There was good correlation between the two methods in detecting hydronephrosis, calculi greater than or equal to 5 mm, and major post pyelonephritic scarring. Urography was superior in detecting small cortical scars, slight caliceal dilatation, and less than or equal to 4 mm calculi. Based on the good results, low cost, and absence of radiation hazards or contrast media reactions, we conclude that ultrasonography may replace urography when a radiological screening of the upper urinary tract is deemed necessary in women with recurrent urinary tract infection. PMID- 2218162 TI - In honour of Professor Peter Armitage. PMID- 2218161 TI - Health problems in Norwegians travelling to distant countries. AB - 373 travellers to countries outside Europe and North America were recruited before departure summer 1988 at the Vaccination Office, Trondheim, Norway, and participated in a follow-up study on health problems related to travel. 313 of the travellers (84%) responded by answering a postal questionnaire one month after return; it dealt with prophylactic measures, life-style, and health problems associated with travelling. An 18% failure in malaria prophylaxis and some risk-taking behaviour related to alcohol and sex were recorded. Diarrhoea (usually mild) was reported by 59%; other symptoms were also frequent. Medical advice was sought by 18% while abroad; 7% consulted a doctor. Ill health made travelling less enjoyable than expected for 8%. After return, 25% had health problems; 9% saw a doctor, three travellers were hospitalized, and 6% were absent from work. Total morbidity was high, but seldom serious. Targeted advice, which can well be given by primary health care personnel, could help to reduce morbidity and risk behaviour and improve travellers' handling of ill health. PMID- 2218163 TI - Sequential stopping rules in clinical trials. AB - This paper reviews aspects of the development of sequential analysis of clinical trial data in medicine and suggests simple strategies for progress. The emphasis is on the pragmatic and ethical requirements of aspects of the design of phase III trials and in circumstances of genuine uncertainty characterized by much clinical experimentation. In particular consideration is given to the consequences of determining sample sizes from incorrect estimates of treatment effects. Armitage's work on sequential trials is traced to simple group sequential procedures based on repeated significance tests to minimize expected sample sizes in a wide class of experimental situations. PMID- 2218164 TI - Must clinical trials be large? The interpretation of P-values and the combination of test results. AB - The notion that small, well planned clinical trials may not be worth undertaking is shown to arise from an overemphasis on just one way of interpreting P-values. Alternative forms of P and other interpretations are put forward. Attention is drawn to some aspects of the theory of hypothesis testing which seem less well known than they should be. PMID- 2218165 TI - How much further investigation? PMID- 2218166 TI - Measuring importance. PMID- 2218167 TI - Repeated measurements: what is measured and what repeats? AB - This paper expresses a personal view of experiments involving repeated measurements; it attempts to classify types of experiment and approaches to statistical analysis: no novel procedures are proposed, only a systematic outlook on objectives and methods. PMID- 2218168 TI - Randomized consent designs for clinical trials: an update. AB - Randomized consent designs were introduced to make it easier for physicians to enter patients in randomized clinical trials. Physician reluctance to participate in randomized clinical trials is often a reflection that the physician-patient relationship could be compromised if the physician makes known to the patient his/her inability to select a preferred therapy. Clinical trials having a no treatment control or placebo amplify this concern. This paper reviews the main ideas of randomized consent designs (single and double) and the statistical model underlying the analysis, and presents some recent experiences. PMID- 2218169 TI - Peter Armitage: a personal recollection. PMID- 2218170 TI - The Armitage-Doll multistage model of carcinogenesis. PMID- 2218171 TI - Time from infection with HIV to onset of AIDS in patients with haemophilia in the UK. AB - The two-stage parametric regression model of Brookmeyer and Goedert has been adapted and fitted to data on the development of AIDS in haemophiliacs in the UK who are seropositive for HIV. The risk of developing AIDS by a given time following seroconversion increases with increasing age at seroconversion. It is likely that the risk increases smoothly with age, although the data have been analysed in three age categories, and it is estimated that by seven years after seroconversion 6 per cent of patients aged under 25 at seroconversion, 20 per cent of those aged 25-44 and 34 per cent of those aged 45 or more have developed AIDS. For a given age at seroconversion the annual risk of developing AIDS increases with increasing time after seroconversion, and at seven years the annual risks of developing AIDS during the next year in the three age groups are estimated to be 2 per cent for those aged less than 25 at seroconversion, and 10 and 11 per cent respectively for those aged 25-44 and 45 or more. PMID- 2218172 TI - An application of density estimation to geographical epidemiology. AB - A relative risk function over a geographical region is defined and it is shown that it can be estimated effectively using kernel density estimation separately for the spatial distribution of disease cases and for a sample of controls. This procedure is demonstrated using data on childhood leukaemia in the vicinity of the Sellafield nuclear reprocessing plant in Cumbria, U.K. Various modifications to the method are proposed, including the use of an adaptive kernel. The final plot demonstrates a sharp peak at Sellafield and a reasonably smooth surface over the rest of the region, despite the small number of cases in the series. PMID- 2218173 TI - The summarizing of clinical experiments by significance levels. AB - For a controlled clinical experiment in which two alternative treatments are compared, the statistical report often culminates in a significance test of the null hypothesis of no difference between the treatments, and significance at the 5 per cent level is taken as positive evidence of difference. It is argued that such an experiment serves primarily an inferential purpose; it is not a simple decision procedure, although its effect on practice may be considered in relation to ethical issues. Statistical inference should not be identified with testing this null hypothesis, despite the emphasis on such tests by R. A. Fisher in his work on design of experiments. This null hypothesis often has no interest or credibility. PMID- 2218174 TI - Bibliography. Publications of Peter Armitage to December 1989. PMID- 2218176 TI - Further papers from the International Society for Clinical Biostatistics international meetings. Gothenburg, Sweden, September 1987 and Innsbruck, Austria, August-September 1988. Proceedings. PMID- 2218175 TI - HIV infection dynamics and intervention experiments in linked risk groups. AB - A multigroup transmission model is described to study the spread of the human immunodeficiency virus (HIV) in linked risk groups. The model permits simultaneous investigation of the increase in the number of persons infected with HIV in three main risk groups: promiscuous homo/bisexual men (two levels of promiscuity), intravenous drug users (men and women) and promiscuous heterosexual men and women. Three modes of transmission are considered: anal and vaginal intercourse and needle sharing. The high dimensional parameter space is connected with the HIV incidence through a transmission matrix. This matrix summarizes the annual effective contact rates due to the three transmission modes. The model helps to clarify which data are needed to disentangle the relative contribution of the within- and between-group transmission routes. The model can be used to perform theoretical experiments. Given a specification of a baseline, the potential use of the model is illustrated by a simulation describing the effect of blocking the transmission through needle sharing. Reference is made to the HIV/AIDS epidemic in The Netherlands. The results of the study show that the model can play a part in the classification of HIV prevalence patterns in linked risk groups, in the study of the interaction between the main risk groups and in the theoretical evaluation of intervention measures. PMID- 2218177 TI - Long term survival analysis: breast cancer and age at diagnosis. AB - The role of age at surgery of breast cancer patients as a determinant of relative survival after making allowance for clinical profile was investigated on a case series of 716 women followed for more than 20 years in one single institution. Multiplicative and additive models for grouped data were adopted to model the standardized mortality ratio and the excess death rate respectively. The models were fitted by the GLIM system assuming a Poisson error function. We conclude that operable breast cancer has a relatively lower impact on total mortality in older patients (65 years or more) than in younger ones and, moreover, the older patients have a more favourable course. PMID- 2218178 TI - Statistical analysis of quality of life data in cancer clinical trials. AB - In clinical trials endpoints other than total and/or disease-free survival are gaining more and more interest. In particular, quality of life (QOL) or the well being of patients has emerged as a synonym for variables describing the subjective reactions of patients towards their disease and its treatment. The statistical analysis of such QOL data is complicated firstly by the large number of variables measured and their obvious lack of objectivity. The construction of suitable aggregate measures allowing a reduction of the measurements into a (preferably) unidimensional index are discussed in the context of an analysis at a fixed time point during the course of treatment. A second problem arises from the consideration that a patient's well-being is subject to changes over time. We discuss the modelling of QOL by suitable stochastic processes which are extensions of a multistate disease process. This allows QOL events to be incorporated into methods of survival analysis by either estimating the relevant transition probabilities between states or calculating quality-adjusted survival times. Finally, some brief guidelines for the planning of clinical trials including QOL measurements will be proposed. PMID- 2218179 TI - The design of case-control studies: the effect of confounding on sample size requirements. AB - This paper considers the extent to which confounding effects of covariates, which are not controlled for by matching in the design, may influence the sample size necessary for case-control studies. The quantitative calculations are performed for an age-matched case-control study on lung cancer and air pollution, and are based on different evaluation methods. For illustrative purposes attention is confined to a dichotomous risk factor and a single dichotomous covariate. By using the numerical values of a pilot study investigating lung cancer and air pollution, it turns out that the sample size required for detecting a relative risk as close as 1.15 to 1 is only slightly influenced by the strength of the association between confounder and risk factor for reasonable variations around our empirical values. On the other hand, sample size considerably increases with increasing relative risk of a confounder even when the association remains small. The sample size required for an individually matched analysis practically equals that for an age-stratified analysis when the relative risk of the covariate is one. With a relative risk greater than one, however, the size for a matched analysis exceeds that for a stratified analysis and the ratio between them increases with increasing relative risk. PMID- 2218181 TI - CTS: a clinical trials simulator. AB - We describe an interactive clinical trial simulation program (CTS), which provides continuous graphical and numerical output as a simulation runs. CTS is capable of simulating trials with two treatment groups and a binary outcome with options for: (1) up to five prognostic subgroups; (2) one of three methods of randomization; (3) equal or unequal allocation of patients to treatment groups; (4) a null or alternative hypothesis; (5) common methodological problems including biased referrals, false positive and false negative outcome reports, non-compliance, dropouts, crossovers, and co-interventions; (6) six methods of dealing with each of these problems; (7) the type I error rate, and (8) stratified or unstratified analysis. In addition, the current results of a trial in progress may be used as the starting point of the simulation to estimate the power of the trial if carried to completion. A few thousand simulations of a user specified scenario is typically entered and executed in about 5 minutes, permitting a student or clinical investigator to explore a variety of scenarios. PMID- 2218180 TI - Efficient evaluation of treatment effects in the presence of missing covariate values. AB - In clinical trials, treatment comparisons are often performed by models that incorporate important prognostic factors. Since these models require complete covariate information on all patients, statisticians frequently resort to complete case analysis or to omission of an important covariate. A probability imputation technique (PIT) is proposed that involves substituting conditional probabilities for missing covariate values when the covariate is qualitative. Simulation results are presented which demonstrate that the method neither violates the size of the treatment test nor introduces additional bias for the estimation of the treatment effect. It allows use of standard software. A clinical trial of breast cancer treatment, in which an important covariate was partly missing, was analysed by Cox's model. The use of PIT resulted in smaller observed error probability compared with case deletion, and sensitivity analysis supported these results. PMID- 2218182 TI - A Markovian model for comparing incidences of side effects. AB - For clinical trials that entail observations at successive visits for the occurrence of a side effect, this paper considers a likelihood-based method to compare side effect incidence rates. The method, which employs the assumption of a Markov chain of order one for the vectors of binary responses, handles missing data due to premature withdrawals. An actual numerical example and a simulated example illustrate the technique. PMID- 2218183 TI - More powerful procedures for multiple significance testing. AB - The problem of multiple comparisons is discussed in the context of medical research. The need for more powerful procedures than classical multiple comparison procedures is indicated. To this end some new, general and simple procedures are discussed and demonstrated by two examples from the medical literature: the neuropsychologic effects of unidentified childhood exposure to lead, and the sleep patterns of sober chronic alcoholics. PMID- 2218184 TI - Applications of global statistics in analysing quality of life data. AB - Quality of life (QOL) instruments usually consist of a number of components, each of which deals specifically with a particular functionally related dysfunction. In a clinical trial whose primary aim is the evaluation of the treatment by means of QOL instruments, analysis of each of the components usually consists of either univariate analysis of variance (ANOVA) or some non-parametric methods. This multiple testing approach can produce an increase in false positive findings. One attempt to correct for this is the Bonferroni adjustment. Another approach is to apply global statistics (parametric or non-parametric) for the null hypothesis of no treatment difference versus the alternative hypothesis that one treatment is uniformly better than the other for QOL instruments as a whole. Data from a randomized double-blind trial of 111 congestive heart failure patients, which involved four QOL instruments, were analysed with univariate ANOVA, Bonferroni adjustment, parametric and non-parametric global statistics. The global statistics complemented the univariate methods and made the presentation of QOL data very effective. I recommend the general use of global statistics in analysis of QOL data. PMID- 2218185 TI - A stratified Wilcoxon-type test for trend. AB - We propose an extension of Cuzick's non-parametric Wilcoxon-like trend test for situations when the observations can be grouped into strata which are thought to be related to the outcome. We illustrate its use in two examples from cancer epidemiology. PMID- 2218186 TI - A two-step method for understanding and fitting growth curve models. AB - With data from a repeated measures design, analysts often overlook growth curve analysis based on the Potthoff-Roy model. The reluctance to perform a growth analysis may result partially from unfamiliarity with the technique, and partially from the lack of readily available computational programs to fit the models. Although growth curve analysis has traditionally appeared as a special technique in multivariate analysis, one can fit the models with the use of two simple ideas: transformation of variables, and weighted least squares (WLS). When presented in this manner, growth models are a natural extension of univariate repeated measures models. Growth curve analyses share with univariate analyses the common objective to limit estimation to a parsimonious set of parameters that characterize the response profiles. One can readily fit models with commonly available software. The two-step methodology also allows the fit of more general growth models that are appropriate when groups have different shape profiles. Two examples illustrate this approach to growth curve analysis. PMID- 2218187 TI - Poisson regression as an alternative to person-time logistic model. PMID- 2218188 TI - The impact that group sequential tests would have made on ECOG clinical trials. PMID- 2218189 TI - Remembrances of Max Halperin. PMID- 2218190 TI - Historical and methodological developments in clinical trials at the National Cancer Institute. AB - The first randomized clinical trial at the National Cancer Institute (NCI), planned in 1954, commenced in 1955 for the treatment of patients with acute leukaemia. The programme in clinical trials at NCI had strong influence from the clinician and administrator, C. Gordon Zubrod, who introduced the randomized clinical trial at NCI and organized the co-operative clinical trials programme of the Cancer Chemotherapy National Service Center (CCNSC) beginning about 1955. The biostatistician, Marvin Schneiderman, collaborated on the first randomized trials in acute leukaemia and solid tumours and recruited the biostatisticians and statistical centres in the early phase of the co-operative clinical trials programme of the CCNSC. From the beginning, there was acceptance of the principles of the randomization of patients and the statistical analysis of data. The sequence of clinical trials for a new agent included the non-randomized phase I (dosage finding) and phase II (preliminary efficacy) trials as well as the phase III (comparison of treatments) trials. New concepts for the treatment of patients developed from 1955 to the mid-1960s included the combination of therapies with independent activity to increase response rates and the administration of therapy to patients in a disease-free (remission) state to prolong the disease-free state. Methodological developments related to clinical trials up to the mid-1960s included: a plan for phase II trials (Gehan); a generalization of the Wilcoxon test for the comparison of survival distributions with right-censored data (Gehan); a test of proportional hazards for survival distributions, which later became known as the Mantel-Haenszel test (Mantel), and an exponential regression model with an explanatory variable (Feigl and Zelen). PMID- 2218192 TI - Some historical and methodological developments in early clinical trials at the National Institutes of Health. AB - This paper reviews five randomized clinical trials with unusual design or analysis features from institutes other than the National Cancer Institute or the National Heart, Lung and Blood Institute. These are: a Cooperative Study of Retrolental Fibroplasia sponsored by the National Institute of Neurological Diseases and Blindness; the Diabetic Retinopathy Study sponsored by the National Eye Institute; the University Group Diabetes Program sponsored by the National Institute of Arthritis and Metabolic Diseases; a Clinical Trial of the Extracranial to Intracranial Arterial Anastomosis (EC/IC bypass) by the National Institute of Neurological and Communicative Disorders and Stroke; and the Clinical Trial of Hereditary Angioedema by the National Institute of Allergy and Infectious Diseases. PMID- 2218191 TI - Early methodological developments for clinical trials at the National Heart, Lung and Blood Institute. AB - The National Heart Institute, now known as the National Heart, Lung and Blood Institute (NHLBI), initiated its first multicentre randomized clinical trials of rheumatic fever and rheumatic heart disease in 1951. The modern era of multicentre trials began, however, when the Coronary Drug Project was initiated in the 1960s. This trial and subsequent NHLBI trials stimulated a wide variety of research on clinical trial methodology. This paper reviews early methodologic developments in four areas. First, an organizational structure for multicentre clinical trials was developed and codified in the 'Greenberg Report' in 1967. Second, design considerations related to patient risk, non-compliance, a lag in treatment effect, and changing risk were explored. The 'intention-to-treat' principle was implicit in these investigations. Thirdly, the concept of periodic review of accumulating data, recommended in the Greenberg report, stimulated research on methods for sequential analysis. Three statistical approaches were developed and investigation of their statistical properties continues today. These approaches are usually described as group sequential, stochastic curtailment, and Bayesian methods. Finally, comparison of treatments in longitudinal studies has been an increasing part of NHLBI research and methods have been developed for design and analysis of longitudinal studies. PMID- 2218193 TI - Application of the triangular test to phase II cancer clinical trials. AB - Phase II cancer clinical trials are primarily designed to determine whether the response rate p to the treatment under study is greater than a specified value p0, that is to test the null hypothesis H0: p less than or equal to p0 against an alternative hypothesis H1 : p greater than p0 specified by p = p1. As an alternative to the single and multistage procedures and to Wald's continuous sequential probability ratio test (SPRT), we applied the group sequential methods proposed by Jones and Whitehead, namely the triangular test (TT) and the discrete SPRT, to the comparison of p with p0, and we expressed H0 and H1 in terms of the log odds-ratio statistic log [p(1 - p0)/p0(1 - p)]. A stimulation study showed that both the TT and the discrete SPRT had type I error and power close to the nominal values, and they compared favourably with multistage methods in terms of the average sample size. PMID- 2218194 TI - Hierarchical models for multicentre binary response studies. AB - A three-stage hierarchical model is proposed for two treatment, binary response studies conducted in a number of centres. The approach adopted is Bayesian. Marginal densities for second stage parameters are shown to provide useful summaries both of comparative efficacy and of the heterogeneity of treatment effects across centres. Sensitivity studies of model assumptions are illustrated. PMID- 2218195 TI - The measurement of change of quality of life in clinical trials. AB - A model is presented for the measurement of change of quality of life in clinical trials with time under the influence of one or more treatments. Quality of life is regarded as a multidimensional latent variable, and is measured through dichotomous item responses on a number of points in time. Change of quality of life is 'explained' with a latent logistic regression model which may include parameters for the time process, the effects of clinical treatments, and interaction parameters. By assuming the absence of patient/time interaction within treatment groups, the parameters of the time process and the treatment effects can be estimated independently of the latent quality of life parameters at the start of the treatment. Consequently, differential mortality, censoring mechanisms, and other mechanisms causing missing data can be ignored. PMID- 2218196 TI - Assessing the gain in efficiency due to matching in a community intervention study. AB - COMMIT (Community Intervention Trial for Smoking Cessation) is a randomized study employing a matched pairs design. Pairs of communities were selected on the basis of their geographical proximity and were chosen to be matched on variables strongly expected to relate to the outcome variable, the smoking quit rate. However, quantitative information was not available to evaluate the efficiency gain from matching. We have used baseline smoking quit rates in the communities as a surrogate for the outcome measure to evaluate the gain in efficiency from the matching. Our method takes account of the possible imperfection of the surrogate as a representative of the true outcome. The method estimates an efficiency gain of at least 50 per cent using the matched design. We also evaluate the further gains in efficiency which would be made by using the baseline quit rate to balance the randomization. PMID- 2218198 TI - Estimating benefits of screening from observational cohort studies. AB - Analysis and interpretation of observational studies of screening effectiveness is difficult because several biases threaten validity, including the structural healthy screenee bias, length bias, and effects of lead time. Although methods for the analysis of observational studies of screening effectiveness have been proposed, most have limitations such as incomplete control of length bias, or a heavy reliance on distributional assumptions. In this report we present a method for the analysis of observational cohort studies of screening effectiveness. Although developed independently and formulated specifically for estimating benefits of screening, our approach is implied by a more general approach developed previously by Robins. Our approach, in contrast to other available methods, avoids the healthy screenee bias, and length and lead time bias, and allows an empirical approach to analysis that need not depend highly on distributional assumptions. We illustrate application of the approach with analysis of published data from a study of breast cancer screening. PMID- 2218197 TI - Modelling forces of infection for measles, mumps and rubella. AB - Serological data from 8870 persons collected prior to the introduction of measles, mumps and rubella (MMR) vaccine in the UK are used to describe the rate at which individuals acquire infection by these diseases at different ages. A parsimonious model is developed and fitted under various interpretations of the data, particularly concerning the probability of lifelong susceptibility to infection. It is shown that, while the force of infection curves are relatively robust in their general features, they exhibit considerable sensitivity in matters of important detail. This is true in particular of the values taken by the force of infection in older age groups. As a result, estimates of the average age at infection are highly sensitive to these interpretations. This in turn may limit the accuracy of predictions from mathematical models based on these parameters, in particular regarding the level of immunization required for eradication of disease. PMID- 2218199 TI - The use of logit models to investigate social and biological factors in infant mortality. V: A multilogit analysis of stillbirths, neonatal and post-neonatal mortality. AB - Infant mortality data for England and Wales, cross classified by mother's age, parity and social class were published for 1949/50 and 1975. Previous analyses of these data have been based on graphical, tabular and logit models of stillbirths, neonatal and post-neonatal deaths separately. This paper summarizes the overall changes in infant mortality using a multilogit model. The model selected is illustrated by appropriate graphical presentations. PMID- 2218200 TI - Proportion cured and mean log survival time as functions of tumour size. AB - We obtained maximum likelihood estimates (MLEs) of the proportion cured pi c and mean log survival time mu t for a sample of 4355 patients with intraocular melanoma whose survival times subsequent to treatment were assumed to follow a log-normal distribution. Following stratification by tumour size, MLEs of pi c and mu t derived for each stratum correlate inversely with tumour size. We then expressed pi c and mu t as continuous functions of tumour size and calculated MLEs for the parameters of these functions from the entire sample. This investigation documents for ocular melanoma a significant relationship of tumour size to both cured fraction and mean log survival time. PMID- 2218201 TI - Homecare at the end of life. A study of fifteen patients. AB - The study is a part of a research project on death in a sector of a large city, involved cooperation with the Franciscan Aid "home care team". The purpose was to study death in the home setting. Fifteen deaths were registered. Participant observation in the care of 14 patients were made--a total of 83 visits to homes, 2-15 visits per patient. In one case the author had contact with the relatives, after the death had occurred. Most of the patients had cancer. Their age varied from 28 to 80 years. The observations were recorded immediately after each visit. After the death of a patient a structured interview with the closest relatives and the nurse responsible were made. Their statements were used as a basis for formulating problems for the further study and the clarification of quantitative data. Results showed that the patients who chose to leave the hospital and remain at home often had negative experiences in hospital. All the patients in this study received good palliative treatment at home. All patients were also informed about their condition. One-third of the patients were readmitted to hospital during the final days. PMID- 2218202 TI - Uniform guidance for medical care. A description of the process for preparing guidelines accepted by different levels of care. AB - Advice by telephone is an important part of primary health care service. Telephone advice is given at different levels of care. In order to give people confidence in the health care system it is important that personnel at different levels give similar advice for the same symptom or complaint. In order to establish generally accepted guidelines, discussions were held between personnel at different levels of care. This procedure was laborious but successful. Generally accepted guidelines could be agreed upon for all the symptoms and complaints discussed, altogether more than 60. This paper describes the procedure used during the collaborative work to provide these guidelines. It must be emphasised, though, that the guidelines should be adapted to local circumstances before being used as a practical aid in the health care service at health centres and at other outpatient units. PMID- 2218203 TI - Prevalence and characteristics of persons with dependency on feeding at institutions for elderly. AB - The prevalence of dependency on feeding was estimated in 3,607 residents cared for in old people's homes, nursing homes, somatic long-stay clinics, psychiatric long-stay wards and psychogeriatric wards. Ten per cent of the residents were found to be dependent on the staff to eat. The highest proportion was found in nursing homes and somatic long-stay clinics. A considerably larger proportion of the residents with dependency on assisted feeding imposed the highest workload on the staff. Residents who were totally dependent on assisted feeding were more disabled with regard to other ADL functions and also they were demented more often. Loss of the ability to eat was related to an inability in other ADL functions. Support was gained for a hierarchical loss of ADL functions as suggested by Katz & Apkom. Feeding problems seem to be a terminal phenomenon in demented patients. PMID- 2218204 TI - Patient-nurse interactions: relationships between person characteristics, empathy, content of communication, and patients' emotional reactions. AB - Relationships between antecedent person variables (sex and age), empathic understanding, content of communication, and patients' emotional reactions were studied in 3200 patient-assistant nurse dyadic interactions. The sample consisted of 32 psychiatric patients (20 males and 12 females, mean age: 61 years) and eight female assistant nurses at a nursing-home in Sweden. Four assistant nurses were younger (25 years old or less) and four were older (45 years old or more). All interactions were regular morning meetings at which the patient's activity plans for the day were discussed. These meetings were held in each patient's private room, and lasted for about 15 min. High empathic understanding on part of the helper covaried with more communication of "everyday character" and communication dealing with "personal and emotional qualities", with less communication dealing with "facts and practical issues", and with a more cheerful emotional state among the patients during the encounters. Male patients were more cheerful during encounters with younger assistant nurses while female patients were more cheerful when interacting with older assistant nurses. Helpers with higher scores on empathic understanding seemed to have a higher awareness of relational history. PMID- 2218205 TI - [Emphysematous pyelitis and pyelonephritis: unrecognized clinical entities]. AB - A case of emphysematous pyelitis occurring in an old diabetic woman is described. The data of the literature about the pathologic agents, the epidemiology and the physiopathology of the disease are reviewed. The approach for diagnosis and the therapy are discussed. PMID- 2218206 TI - [Peri-colostomy hemorrhage due to portal hypertension secondary to hepatic metastasis of a rectal adenocarcinoma. Apropos of a case report. Literature review]. AB - The authors present a case report of recurrent peristomal variceal bleeding resulting from portal hypertension induced by hepatic metastases of a rectal cancer. They propose mucocutaneous disconnection as a simple and effective palliative surgery in order to prevent new bleeding. Discussion is based on a review of the literature and illustrates the different therapeutic options for this complication. PMID- 2218207 TI - [Differential diagnosis of giant-cell bone tumors]. AB - Beyond the "myeloplax tumor", other tumoral bony lesions, essentially benign, present "osteoclast-like" giant multinuclear cells at the time of the anatomo pathologic examination. Generally, the differential diagnosis of these bony lesions with giant cells is due to the conjunction of several data such as the age of appearance of the lesion, bony location, radiological aspect, anatomopathological aspect, etc. PMID- 2218208 TI - [Sudden death in athletes]. AB - In France, about one of ten thousand athletes die suddenly each year. Although this is a small proportion of the number of total deaths, it is a striking one because of the subjects it concern e.g: healthy and physically trained. Age is the major determinant cause of sudden death: coronary heart disease in victims over 35 years, hypertrophic cardiomyopathy, congenital disease and aortic rupture before. Positive predictive value of usual tests is given; high value of echocardiography is to be noted, in comparison with low value of the traditional stress test for detection of subjects at risk. PMID- 2218209 TI - [Current progress in antifungal therapy: the value of fluconazole]. AB - Invasive fungal infections are major problems in immunocompromised patients and optimal therapeutical modalities are still far from optimal. Recently, progresses of antifungal therapy have been achieved with the development of new antifungal agents. In particular, fluconazole seems very promising due to the availability of oral and intravenous formulations. Tolerance and compliance of patients are excellent and side effects as well as interaction with other drugs are less commonly observed than with other antifungal agents available so far. The major indications of fluconazole are candidiasis and cryptococcosis. PMID- 2218210 TI - [Spastic colon: a multi-factorial pathology, a polyvalent therapy]. AB - Irritable bowel syndrome represent the most common gastrointestinal disease. It is characterized by abdominal pain, distension and abnormalities of intestinal transit. It is a functional disorder determined by emotional stress and by diet. The treatment is polyvalent, dietary, medicinal and psychological. In the medicinal domain the anti-spasmodics (anti-nicotinic and musculotropic), represent the first choice weapons in association or not with an anxiolytic, an anti-depressor, even an antalgic in the acute phase. PMID- 2218211 TI - [Diuretics: mechanism of action and therapeutic indications]. PMID- 2218212 TI - [Opioid peptides and obesity]. PMID- 2218213 TI - [Hepatic fibrosis with cirrhogenous development in chronic vitamin A poisoning]. PMID- 2218214 TI - [Collagenous colitis, achlorhydric gastritis and IgG deficiency]. PMID- 2218216 TI - [Pharmacotherapy in the elderly]. PMID- 2218215 TI - [Protothecosis and chlorellosis, 2 infections induced by algae]. PMID- 2218217 TI - [Hyperthyroidism in the elderly]. AB - Hyperthyroidism is a frequent disease in elderly people. Its diagnosis is often difficult, as its clinical presentation is atypical, with few symptoms. Results of laboratory tests can be difficult to interpret, because of physiological changes due to old age, and small abnormalities. Diagnostic and therapeutic procedures, as a function of aetiology, are discussed. PMID- 2218218 TI - [Diabetes in the elderly. Reflections by a practitioner in diabetology]. AB - Above 70 years of age, it is no more necessary to be obsessed by the prevention of late complications in introducing an intensive treatment. A symptomatic one, particularly with insulin is more appropriate. Before treating diabetics it is necessary to search symptomatically for aggravating factors like the use of thiazide or intercurrent diseases. PMID- 2218219 TI - [What is your diagnosis? Pre-excitation syndrome with consecutive repolarization disorder]. PMID- 2218221 TI - [The skin of the aged]. AB - This is a review of physiological changes and photo-aging of the senescent skin and of their clinical aspects. It also contains a discussion of the origins pruritus in elderly people. PMID- 2218220 TI - [Treatment of arterial hypertension in the elderly person: unresolved problems]. AB - There is not increasing evidence that, from an epidemiological stand-point, treatment of diastolic hypertension in the elderly leads to a significant cardiovascular risk reduction; however, for the individual patient, the magnitude of absolute risk reduction is relatively small. More widespread use of ambulatory blood pressure recording is suggested in order to improve patient selection - i.e. to avoid antihypertensive treatment in patients with white coat hypertension - and to prevent overtreatment in patients with established hypertension. This strategy should result in a selection of elderly, hypertensive patients who are more likely to benefit from pharmacological treatment and thus restrict the number of patients needing treatment for prevention of a cardiovascular complication. Furthermore, by decreasing the risk of overtreatment, this strategy is likely to result in a decrease in the number of medication-related side effects such as coronary morbidity and mortality. PMID- 2218223 TI - [Heart and heart-lung transplantation]. PMID- 2218222 TI - [What is your diagnosis? Generalized hydroxyapatite disease]. PMID- 2218224 TI - [Prevention of HIV infection in the methadone program. A study of a drop-in clinic in Zurich]. AB - We were able to show for 21 patients who were all HIV-negative at the beginning of the methadone maintenance program of the Drop-in in Zurich that they remained HIV-negative over an average period of 34 months. At the beginning of the program 48% of the patients had a good social integration with few contacts to the drug scene for buying or selling drugs. During the program this figure increased to 90%. Before starting the program 43% of these HIV-negative patients were at high risk (needle sharing). During the maintenance program 57% of the patients became clean of heroin and 76% clean of cocaine. The remaining obviously abstained from needle sharing due to a continuous information concerning HIV-prevention. We conclude that a well structured methadone maintenance program with a close, consistent and enduring relationship between staff and patients can be of great importance in HIV-prevention among IV drug abusers. PMID- 2218225 TI - [Arthritis of the hip associated with infantile toxocariasis]. AB - A parasitic origin of rheumatological manifestations is only suspected if the patient returns from an endemic area of the world. We report a young girl who developed without travelling, an isolated hip arthropathy simultaneously with a Toxocara infestation. Pathogenesis is discussed. PMID- 2218226 TI - [The current significance of spinal cord stimulation in the framework of functional neurosurgery]. AB - Spinal cord stimulation (DCS) has proved effective in different types of Deafferentation Pain. Long-term results are good in 60-85% of cases. DCS improves microcirculation and ischemia in cases of inoperable peripheral vascular diseases. Advantages of this method are: Absence of severe complications and estimation of the effect during the test phase. - Nevertheless, other neurosurgical possibilities (destructive pain surgery, spinal/cerebral application of medicaments) continue to preserve their indications. PMID- 2218227 TI - [Severe vomiting, diarrhea]. AB - Because of heavy vomiting and a watery diarrhoea after consumption of two Amanita phalloides mushroom taken in suicidal attempt this 31-year old female patient came to our emergency ward. The diagnosis being clear a therapy with stomach irrigation, substitution of fluid and electrolytes as well as application of penicillin and Silibinin was begun. The toxin concentration in the urine was not too high and the Quick value did not fall to low. The course was benign and the patient could leave the hospital only a few days later. PMID- 2218228 TI - [A case from practice (187). Lactose intolerance]. PMID- 2218229 TI - [A case from practice (188). Temporal lobe epilepsy. Arterial hypertension. Obesity]. PMID- 2218231 TI - [From curative to preventive medicine: integral prevention as exemplified by cardiology]. PMID- 2218230 TI - [What is your diagnosis? Herpes zoster]. PMID- 2218232 TI - [Primary prevention of coronary heart disease: possibilities and limitations]. AB - Cardiovascular diseases are still the most important cause of death in industrialized countries. In spite of enormous progress regarding prevention, diagnostic and therapeutic procedures, coronary heart disease remains the most important cardiovascular cause for early invalidity, professional inactivity and premature death. The direct and indirect costs of cardiovascular diseases amount to 14.8% of total disease-related costs. The practicing physician has an important role to play in the prevention of cardiovascular diseases. In order for the physician to understand his critical role and to act accordingly, some fundamental epidemiological principles are introduced. Particularly, the notion of population attributable risk is important: As a consequence for the health of whole population groups, it is as important to advise the many at intermediate risk as the few at high risk of a cardiovascular accident. The future challenges are clear. This disease group is to a large extent preventable; efficient intervention models, both on an individual and on a community level, are available. PMID- 2218233 TI - [Nutrition and hypertension: what are the goals?]. AB - The dependence of blood pressure on nutritional factors is reviewed in the light of possible therapeutic consequences. Salt restriction, increased administration of potassium, restriction of alcohol intake, weight loss and prescription of fish oil are discussed by review of own and published data. All these measures may contribute to a reduction of hypertension although to a variable extent. They should be envisaged as therapeutic alternatives to drugs in mild hypertension. PMID- 2218234 TI - [Smoking and smoking cessation in the context of preventive cardiology]. AB - Knowledge about the effects of smoking on the development of cardiovascular disease is constantly growing. As an example, we know today that myocardial infarction is more frequent among smokers, also among monozygous twins, and that the relative risk of women who smoke is comparable to that of male smokers. The mechanisms of action are in atherogenesis, in the stimulation of the adrenergic system and in an increase of plasma fibrinogen. In order to best support his patients to give up smoking, the practicing physician has to be aware of the factors influencing the smoking habit. The parallel development of psychological dependence and physical addiction to nicotine is described, and it is shown how nicotine substitution therapy can help to stagger psychological and physical withdrawal. The introduction of transdermal nicotine substitution opens new possibilities in this context. PMID- 2218235 TI - [Physical activity and coronary heart disease]. AB - Epidemiological data suggest that in middle aged men a regular physical activity, occupational or in leisure time, may protect against a first coronary event. Randomized clinical trial of cardiac rehabilitation after myocardial infarction, including physical training, has shown a positive trend for reduced rates of all cause death and coronary death in the intervention group. Although not statistically significant, physical training in coronary patients is recommended because the benefits of training include an improved exercise tolerance and risk factor profile. Furthermore, supervised cardiac exercise programmes appear to be safe for the average patient, with the possible exception of some patients with large anterior wall infarctions who might deteriorate and have, therefore, to be closely controlled during rehabilitation. PMID- 2218236 TI - [Re article: "The development in medicine in the Werdenberg-Sargan region" by Dr. M. Gassner, "Schweiz. Rundschau Med.(PRAXIS)" 79, No.8, pp. 193-201, 1990]. PMID- 2218237 TI - [What is your diagnosis? Deficient excitation of the ventricular electrode]. PMID- 2218238 TI - [Urological sexology]. PMID- 2218239 TI - [Serum cholesterol of Swiss military personnel and assessment of nutrition in military service]. AB - Two separate studies are reported. The first aimed at assessing the prevalence of hypercholesterolaemia in 453 military personnel who were in service in fall 1988 in a military fort. According to the risk limits of the Swiss Working Group on Lipids, the serum cholesterol values were elevated in 30% (greater than 6.5 mmol/l), in the borderline range in 31% (5.2. to 6.5 mmol/l), and only 39% had values in the ideal range (less than 5.2 mmol/l). There was a significant correlation of serum cholesterol (measured by Reflotron) with age, and the increase between age 20 and 40 was particularly remarkable (1.5 mmol/l increase). There was also a significant correlation of serum cholesterol with body weight. Only 9% of the soldiers knew their cholesterol levels before the study. One third were smokers, and 9% were hypertensive. The second aimed at analysing the consumption of food in the military service. This analysis was performed during a military service in an underground fort, where all food was controlled and known. The analysis indicated that per subject and day, 2051 kcal daily were consumed from the troup kitchen. Additional calories were consumed in the canteen (before and after the main meals) in the form of sweets, particularly as beverages. There were 1053 kcal per person and day consumed in the canteen, consisting of 39% carbohydrates, 36% fat, 15% proteins and 10% alcohol. The study demonstrates on one hand, that a significant number of military personnel demonstrates undesirably high serum cholesterol concentrations; on the other hand, the second study shows that too many calories are consumed during military service and that the foodstuff was too high in fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218240 TI - [Erectile dysfunction of male spinal cord injury patients]. AB - Different problems regarding erectile dysfunction in men with spinal cord-injury are outlined. Neuroanatomical and neurophysiological aspects of erection and ejaculation are outlined and brought into relation with the different clinical pictures of such lesions. Different therapeutical possibilities are presented, particularly the new treatments like intracavernous papaverine (autoinjection), prostaglandin E1 and transcutaneous nitroglycerin; action, advantages and indications are discussed. The experience in ten para- or tetraplegic patients are discussed. It seems that even in spite of the higher price of PGE1 this treatment of the erectile dysfunction in spinal cord-injured men should be preferred, since it shows more advantages and less complications than other treatments. PMID- 2218241 TI - [Aspects of Balint group activities]. AB - The working with Balint groups is one of the best known instruments to teach doctors a 'psychosomatic' or a 'psychosocial' approach to their patients. Three case studies are reported. Apart from case-related knowledge, the particular attitude of this patient-oriented medicine is discussed. Characteristics of Balint groups and the changing of a therapist's opinion are listed. PMID- 2218242 TI - [Typical nosocomial infection with an unusual cause: Hafnia alvei. Report of 2 cases and literature review]. AB - The route of infection and the course of two typical nosocomial infections are described in two patients infected with a rare gram-negative bacterium. Both patients underwent cardiovascular surgery. They were placed close to each other in the intensive care unit for several days and suffered from pneumonia and from wound infection respectively. In both patients bacterial culture grew Hafnia alvei. Successful antibiotic treatment was achieved with Netilmicin and Imipenem. Urinary tract, respiratory tract and wound infections are the most frequent nosocomial infections according to the literature. Risk factors are duration of stay in the intensive care unit, shock, poor general condition and advanced age. PMID- 2218243 TI - [A case from practice (198). 1. Radiation-induced proctocolitis with anemia provoking hemorrhage following irradiation of a stage IIIb cervix carcinoma in 1987. 2. Type II diabetes mellitus]. PMID- 2218244 TI - [A case from practice (190). Cerebrospinal syphilis. Personality disorders. Alcohol and drug abuse]. PMID- 2218245 TI - [What is your diagnosis? Acute bacterial endocarditis]. PMID- 2218246 TI - [Stress: a treatable cardiovascular risk factor?]. AB - The study of psychosomatic factors in the pathogenesis of ischemic heart disease has followed three directions, a clinical-phenomenologic, physiologic-behavioral and a curricular-psychodynamic one. From the sixties onward Type A behavior has been prevailing as concept for the investigation of prospective importance of psychic factors in ischemic heart disease. Such a behavior-oriented view alone proves however to be inadequate. For a comprehensive approach to psychic risk factors and their treatment and prevention anxiety, depression, important experiences in life and individual biographic constellations are equally important. They represent factors only approximated by the conventional term "stress". PMID- 2218247 TI - [Lipid-lowering therapy in the prevention of coronary heart disease]. AB - Reasons for the current emphasis on cholesterol as coronary risk factor are multiple. On one hand current studies have shown that primary as well as secondary prevention of ischemic heart disease is a realistic possibility with lipid lowering measures. On the other hand new drugs are actually available which permit a potent and adapted therapy of hyperlipidemias. According to new guidelines of the Swiss "lipid task force" screening for hypercholesterolemia is recommended. A cholesterol value greater than 6.5 mmol/l should be investigated and treated. Because a great proportion of adult Swiss fall into this category (approximately 1/3) it is essential that all those are efficiently treated that have markedly abnormal cholesterol values or present with other risk factors such as smoking and hypertension or have a personal or familiar history of ischemic heart disease. Because progression is likely in patients with or after manifest ischemic heart disease even when hypercholesterolemia is mild (over 5.2 mmol/l) all patients presenting with an infarct should be investigated for dyslipidemia. Cholesterol, triglycerides and HDL should be determined. Dietary measures are the basis of every attempt to reduce hyperlipidemia. Most importantly intake of saturated fats prevailing in animal products should be restricted. The next important step is reduction of dietary cholesterol and in obese patients also caloric restriction. Lipid lowering agents are recommended in patients at risk who do not respond to or comply with dietary regimens. According to type of dyslipidemia bile-acid-binding resins, fibrates, nicotinic acid or HMG-CoA reductase inhibitors are available. PMID- 2218248 TI - [Antihypertensive therapy and prevention of hypertensive complications]. AB - Arterial hypertension is one of the most important risk factors for the high cardiovascular morbidity and mortality. The efficacy of treatment is undisputed in patients with severe or accelerated hypertension. For the majority of patients suffering from mild to moderate hypertension the usefulness of treatment is not as well established although the potential benefit would be greatest. In this group the reduction of cerebrovascular complications has been demonstrated whereas reduction of morbidity and mortality for ischemic heart disease has remained controversial, indicating that reduction of blood pressure alone may not sufficiently reduce the risk for coronary complications. In contrast to cerebrovascular disease ischemic heart disease depends probably on several risk factors other than hypertension. For prevention of ischemic heart disease these other factors therefore need to be considered extensively. PMID- 2218249 TI - [Thrombocyte inhibitors in cardiovascular therapy]. AB - An increased platelet-vessel wall interaction plays an important role in most forms of cardiovascular disease. In healthy arteries, the vascular endothelium prevents platelet adhesion and aggregation. As a mediator of this protective function, the endothelium produces prostacyclin, endothelium-derived nitric oxide and tissue plasminogen activator. Cardiovascular risk factors such as hypertension, hyperlipidemia and diabetes are associated with an increased platelet activation and with decreased antithrombotic properties of the blood vessel wall. The available inhibitors of platelet function interfere only with one of various mechanisms of platelet activation and of the platelet-vessel wall interaction. Prostaglandin inhibitors, such as aspirin and newer, more specific inhibitors, prevent the production and/or the effect of thromboxane A2 on platelets and the blood vessel wall. Other drugs interfere with the effect of adenosine diphosphate on platelets, or they increase intracellular concentration of cyclic GMP or AMP in platelets and vascular smooth muscle cells. The protective effects of platelet inhibitors in primary and particularly in secondary prevention of cardiovascular diseases have been documented in numerous studies. The successful clinical use of these substances, however, requires a selective prescription of the drugs in patients with cardiovascular disease. PMID- 2218250 TI - [A bayliff's kind of medicine]. PMID- 2218251 TI - [Drugs and liver function]. PMID- 2218252 TI - [Restaurant asthma]. PMID- 2218253 TI - [Clinical aspects of hypothermia]. PMID- 2218254 TI - [Significance of micro-albuminuria]. PMID- 2218255 TI - [Sleep apnea syndrome: a new diagnostic entity?]. PMID- 2218256 TI - [Jaundice. Clinical discussion]. PMID- 2218257 TI - [Various carcinogenesis risk factors of radiotherapy]. PMID- 2218258 TI - [The echocardiographic characteristics of cardiac lesions in beta-thalassemia]. AB - The authors submit the results of clinicoechocardiographic investigations of 35 patients with beta-thalassemia aged from 4 to 37 years of whom 23 patients were with acute beta-thalassemia, 6 with an intermediary form and 6 with a heterozygotic form of the disease. Various echocardiographic changes were observed in patients with acute and intermediary forms of beta-thalassemia, i.e. prolapse of the mitral valve (52 and 50 per cent), the presence of fluid in the pericardium (13 and 17 per cent), structural changes in the valvular apparatus (56 and 83 per cent), disorders of the inotropic and diastolic functions of the heart. PMID- 2218259 TI - [Roentgeno-morphological comparisons in rheumatoid arthritis based on data of a long-term prospective study]. AB - During a prospective observation lasting 6 years 68 patients with rheumatic arthritis (RA) were repeatedly examined (up to 8 times) roentgenologically with parallel puncture biopsy of the synovial fluid of the knee joint made with an atraumatic needle, and numerical evaluation of markedness of 25 morphological signs of synovitis. A comparative analysis of the markedness of morphological signs of synovitis in relation to the degree and dynamics of destructive changes in the knee joint was made on the basis of the findings of 254 puncture biopsies and the same amount of roentgenograms. There is a close relationship between the activity of synovitis and the progress of destructive arthritis except for the morphological signs characterizing the reaction of hypersensitivity of an immediate type that may serve the purpose of prognostication of further articular destruction and of the choice of an early adequate therapy. PMID- 2218260 TI - [Dynamics of the basic statistical indices in rheumatic diseases]. AB - The authors have analysed the State statistics data concerning the Soviet Union for 10 years with respect to the changes in the indices for morbidity, prevalence, invalidity, fatality and temporary incapacity for work in rheumatism and chronic diseases of the joints. It has been established that on the one hand the health of the population suffering from rheumatic fever improves but on the other hand the prevalence of chronic diseases of the joints according to the attendance to polyclinics and temporary incapacity for work due to diseases of the osteomuscular system steadily increase. The task of the rheumatological service of the country is to improve organization of effective prophylactic medical examination and therapy of patients with rheumatic diseases of the joints. PMID- 2218261 TI - [The clinical value of determining beta-glucuronidase activity in the cells and blood serum of patients with systemic scleroderma]. AB - The spectrophotometric method was used to determine the activity of beta glucuronidase (BGU) in the cells (neutrophils, mononuclear cells, thrombocytes) in the blood serum of patients with systemic sclerodermia (SSD). The authors revealed a synchronous change in the activity of BGU in all the cells and in the blood serum, and also a decrease in the activity of the enzyme in the concentration of protein in neutrophils, it being very significant in patients with SSD accompanied by trophic changes. There was a direct relationship between the activity of BGU in the blood serum and the level of C-reactive protein and an inverse one between the activity of BGU and the content of circulating immune complexes in the blood. The level of BGU in the blood serum reflects not only the activity of the inflammatory process but also the markedness of trophic changes in patients with SSD. PMID- 2218262 TI - [Do non-steroidal anti-inflammatory agents possess antioxidant activity?]. PMID- 2218263 TI - [Evaluation and prognosis of work capacity in rheumatoid arthritis]. AB - Assessment of the functional state, social and psychological status of 82 patients with RA was made with the aid of a modified health assessment questionnaire (HAQ) and individual arthritis impact measurement scales (AIMS). A group of disabled persons exhibited a greater markedness of articular destruction, high activity of the disease and a high functional index, all of them being old persons. Patients with working ability underwent prophylactic medical examination, more intensive therapy with basic drugs. The use of a computer for prognostication of capacity for work has been shown. PMID- 2218264 TI - [The microbiocenosis of the intestines and its influence on the course of postenterocolitic reactive arthritis]. AB - The authors studied microbiocenosis of the intestine and its influence on the course of postenterocolitic reactive arthritis in 43 patients. The data obtained confirm the participation of intestinal dysbacteriosis in the development of a chronic form of reactive arthritis. The favourable effect of sour milk bifidumbacterin on articular manifestations in postenterocolitic reactive arthritis has been noted. PMID- 2218265 TI - [Exogenous and endogenous risk factors in rheumatoid arthritis (review of the literature and personal data)]. PMID- 2218266 TI - [A case of an unusual lesion of the lungs in rheumatoid arthritis]. PMID- 2218268 TI - [A study of Raynaud's syndrome using dynamic infrared thermography]. AB - The method of infrared thermovision was used to study 22 patients with Raynaud's syndrome: 9 patients with sclerodermia, 8 with the primary Raynaud's syndrome and 5 patients with various rheumatic diseases. Patients with recurrent Raynaud's syndrome exhibited adaptation disorders, anomalous distribution of temperature- warming up began not from the distal regions of the bones, as it happens in the norm and with the primary Raynaud's syndrome, but from the proximal regions. Functional tests for sympathetic activation showed the absence of excess reaction in all the groups under examination. Direct cooling of the hand in patients with recurrent Raynaud's syndrome was accompanied by a considerable delay in restoration of the initial temperature. Sublingual administration of nifedipine did not induce a rise in skin temperature in 6 out of 9 patients with sclerodermia. Marked disorders in microcirculation in patients with recurrent Raynaud's syndrome were observed. The role of injury inflicted to arteriovenous anastomoses in pathogenesis of the mentioned syndrome are discussed. PMID- 2218267 TI - [Remission of rheumatoid arthritis--myth or reality?]. AB - Proceeding from a long-term observation of 956 patients with RA (rheumatoid arthritis) the authors discuss the problem of its remission. Spontaneous remissions of the disease are possible but in most of the cases remission comes as a result of therapy. Lengthy remission (from one to five years) was attained in 14 per cent of the patients, steady remission (not more than five years) in 8 per cent of the patients. The following types of remission are distinguished: spontaneous remission, genuine remission changing the nature of RA course, therapy-induced remission, sham remission no modifying the nature of the process. Different types of remission have been analysed. Importance of correct evaluation of remission in prognosticating the course of RA and the choice of the most effective treatment plan has been analysed. PMID- 2218270 TI - [Gingival preparation]. AB - For the general practitioner, the superficial periodontal structure is an obstacle when trying to gain access, control and visualization to juxta or infra gingival preparations. A temporary restoration will maintain and protect those limits and in many cases it is a very efficient procedure. Sometimes it is necessary to enhance the gingival preparation by sophisticated methods. There are many different technics available to the practitioner. In this article we will describe the technics with easy clinical use and those respecting the gingival tissue (mechanical, physico-chemical). PMID- 2218271 TI - [Reversible hydrocolloids]. AB - Reversible Hydrocolloids impressions are the most simple, easy and reliable of all the available impression technics, when their indications are respected. The precision of this technic, although excellent, can not render this technic universal. The indications and limitations of this technic are directly related to the properties of the reversible hydrocolloids. Good clinical results will depend on: a very good gingival retraction technic (with enough space for the material) and the immediate casting of the impression; the knowledge of the intrinsic qualities and performances of the material during all the clinical steps, without trying to surpass or betray those qualities. PMID- 2218269 TI - [Fundamental properties of impression materials]. PMID- 2218273 TI - [Full impressions with silicone elastomers. The wash technic]. AB - The wash-technic is one of the most well known and most used impression technic when using elastomeric silicones. It is however one of the most criticized technic. The wash-technic depends on Biomaterials and on operative procedures. After reviewing the two types of elastomeric silicones available and the properties that are required for this technic, the author shows that additive materials are reliable and successful when used for the wash-technic. Nevertheless to eliminate all possible deformations due to internal tensions of the materials, it is very important to follow strict operative procedures (specially for the pre-impression preparation), and to respect the contra indications of this technic. PMID- 2218272 TI - [Hydro-alginates]. AB - Hydro-alginates are a combination of reversible and irreversible hydrocolloids. These products are a material choice in fixed prosthodontics and removable partial denture due to their reliability and ease of use, depending on adequate utilization of the materials and on a perfect synchronization during the impression procedures. PMID- 2218274 TI - [A custom grooved impression tray]. AB - Individual compartment trays can be used for dental impression in fixed prosthodontics and represent an original method which alleviates the pitfalls of standard technics. This method is based upon a strict adaptation of the tray to both the preparations and the dental arcade using the primary impression. Impression pastes can be used in their optimal conditions using the I.C.T. (Individual Compartment Trays) and a higher definition of cervical limits can be obtained. The use of I.C.T. reduces the risks of interposing free marginal gingival and eliminates the inconvenients of intrasulcular leakage. PMID- 2218275 TI - [Full band impressions]. AB - Complete impression with rings achieves the same definition than complete impressions alone and gives a final quality similar to unitary guided impressions. The required steps are the following: 1st clinical: adjustment of the unitary rings, laboratory: elaboration of metallic resin boxing and individual tray, 2nd clinical: complete impression with rings. This method is of a particular interest because of its facility and its possible adaptations to various impression pastes or clinical situations. No gingival conditioning is required to the impression, and increased indications of the method can thus be seen when esthetics or periodontal conditions are a priority. PMID- 2218276 TI - [Modification and development of gingival tissue during eruption of permanent teeth]. PMID- 2218277 TI - [Transposition of permanent canines and its prevention: a preventive approach]. PMID- 2218278 TI - [Eruption failure of lower second premolars]. PMID- 2218279 TI - [Role of surgery: early germectomy and rationale of the first premolar]. PMID- 2218280 TI - [Early treatment of severe dento-maxillary dysharmony: eruption guidance of incisors and canines]. PMID- 2218281 TI - [Intraosseous malposition of tooth germs: surgical treatment, results]. PMID- 2218282 TI - ["Education" of shape memory wires: utilization (2)]. PMID- 2218283 TI - ["Battery" in the face]. PMID- 2218284 TI - [Lingual brackets without ligatures]. PMID- 2218285 TI - [Detachable anchorage splint]. PMID- 2218287 TI - [Intrathoracic Pott's abscesses, radiologic pitfalls for the pneumologist]. AB - The authors have conducted a retrospective study of 200 cases of tuberculous spondylitis, and wish to draw attention to the clinical and, chiefly, radiological aspects of the disease. Intrathoracic Pott's abscesses are principally observed in developing countries but they are not exceptional in France, and their varied semeiology deserves to be described. PMID- 2218286 TI - [Intestinal perforation occurring at the beginning of treatment: a severe complication of bacillary tuberculosis]. AB - We report 2 cases of intestinal perforation caused by tuberculosis and affecting the small intestine in one case and the colon in the other case. The patients were men aged 49 and 51 years respectively. Both were cachectic and presented with advanced open pulmonary tuberculosis. Perforation in free peritoneal cavity occurred 2 and 8 days respectively after an antituberculous treatment was initiated. The outcome was rapidly fatal in both cases. Tuberculous enteritis has become rare, but it can still be observed in patients with severe open pulmonary tuberculosis, where the gastro-intestinal tract is contaminated by the large number of virulent mycobacteria swallowed. In such patients clinicians must be alert to abdominal premonitory signs. Intestinal perforations in free peritoneal cavity are uncommon. Most perforation are small, single or multiple, and located on the antimesenteric side of the terminal ileum. They may occur at any time, and particularly just after an antituberculous therapy has been instituted. Clinical presentation is one of acute peritonitis requiring emergency laparotomy. Mortality has been reduced by technical improvements, notably temporary enterostomy, but perforation remains a serious and often fatal complication of tuberculosis in patients with severe malnutrition. PMID- 2218288 TI - [Respiratory diseases at hospitals in Brazzaville, Congo]. AB - The authors has recorded all respiratory diseases encountered in the chest department of the University Hospital of Brazzaville, from January 1 to December 31, 1988. The case-records of 912 patients were involved in this study. Respiratory disease were found to be more frequent in men than in women. Tuberculosis ranked first (52.08%), followed by acute lung infections (32.65%) and asthma (5.15%). Malignant tumours were rare (1.53%). The incidence of HIV infection was high (10.51%), and this disease was often associated with tuberculosis (10.30%). Subjects in the 20-29 years age group were those most affected. The overall mortality rate was 13.48%. Mortality increased with age, exceeding 30% in patients over 60. Mortality rates were 15% in acute lung infections and 10% in tuberculosis. PMID- 2218289 TI - [Pseudotumoral "pedicled" juxta-diaphragmatic opacities]. PMID- 2218290 TI - [Isolated pleural actinomycosis. Apropos of 2 cases]. AB - Two cases of isolated pleural actinomycosis are reported. This form is much less frequent than the pulmonary form, and it accounts for only 20% of thoracic actinomycoses. The bacteriological diagnosis is easily obtainable by pleural puncture, provided it has not been obscured by previous antibiotic therapy and provided the organism has systematically been cultured under anaerobic conditions. Pleural actinomycosis has a very favourable prognosis. Local treatment, sometimes surgical, is indispensable. If the condition is diagnosed at an early stage, systemic antibiotic therapy can be reduced to 6 to 12 weeks. PMID- 2218291 TI - [Plasma cell granuloma of the lung. Apropos of a case and review of the literature]. AB - A case of plasma cell granuloma of the lung is presented, and the clinical, radiological, histological, diagnostic and therapeutic data obtained from 97 published cases are reviewed. Since the disease is usually peripheral, the diagnosis rests on surgical biopsy and histological examination. In the case presented here, it was established on intrabronchial biopsy obtained by fibroscopy. PMID- 2218292 TI - [Environmental interstitial pneumonia caused by asbestos. Study of a Turkish family exposed to tremolite]. AB - Environmental exposure to asbestos, as observed in Anatolia (Turkey), usually results in pleural pathology (plaques and mesothelioma). We report the case of a 50-year old woman who, until the age of 50, had lived in Eregli, central Anatolia, a region where inhalation of environmental asbestos is responsible for a high prevalence of pleural diseases. Radiology showed diffuse interstitial pneumonia without pleural involvement. Bronchoalveolar lavage brought back asbestos bodies (AB) in concentrations of 4,250 per millilitre. All were made of tremolite, a non-commercial variety of asbestos. The patient's family was investigated by chest radiography and search for AB in sputum. The husband, who came from the same town as his wife and had been exposed until the age of 45, had the classical response with bilateral pleural thickening but no parenchymal abnormalities; 2 AB were found in his sputum. The 3 sons, exposed for 10, 13 and 20 years respectively, had normal radiograms and no AB in their sputum, except for the older (3 AB) who had been exposed for 20 years. These cases illustrate the importance of environmental exposure to asbestos which may produce lesions similar to those observed in industrial exposure. Only mineralogical examinations can determine whether the asbestos is environmental or industrial. PMID- 2218293 TI - [Apropos of 2 cases of hemolytic anemia in mycoplasma pneumonia]. AB - The authors present 2 cases of mycoplasmal pneumonia associated with severe haemolysis. Haemolytic anaemia is a well-known and habitually mild complication of the disease. It is related to a peak of cold agglutinins, which are antibodies that agglutinate red blood cells usually at low temperatures but sometimes at 37 degrees C when they are present in high concentrations. The pathogenesis of cold agglutinins is thought to involve the secretion of peroxides by Mycoplasma pneumoniae with alteration of ed cell antigens which become immunogenic. PMID- 2218294 TI - [Broncholithiasis in a case of silicotuberculosis]. AB - Broncholithiasis is usually a late complication of tuberculous lymphadenopathy. Clinical symptoms are not suggestive of the condition in most cases, except for lithoptysis which occurs in 5 to 34% of the patients. Owing to the currently low frequency of tuberculosis, broncholithiasis is a rare and sometimes surprising diagnosis, as in the case reported here. In this 65-year old silicotic man, broncholithiasis was manifested by blood-stained expectoration. Fibroscopy established the diagnosis by showing 2 broncholiths, about 1 cm wide, which were endoscopically extracted. The second peculiarity of this case is that broncholithiasis was associated with active tuberculosis. PMID- 2218295 TI - [Consensus development conference: diagnosis of nosocomial pneumonia in intensive care. 5th consensus conference in resuscitation and intensive care medicine (October 13, 1989)]. PMID- 2218296 TI - [Natural history of systemic lupus erythematosus: the experience at the Arnaldo Vieira de Carvalho Cancer Institute]. AB - The authors present an evaluation of sixty patients with SLE who were observed at the "Arnaldo Vieira de Carvalho" Cancer Institute from 1980 to 1988. Their findings were compared to findings of other international series. Some differences were observed in the frequency of clinical manifestations, laboratory findings, and mortality. PMID- 2218297 TI - [Immediate breast reconstruction and oncologic criteria: our current definition]. AB - After a review of the literature, the authors attempt at a definition of the oncologically safe candidate to an immediate reconstruction after modified radical mastectomy for breast cancer. The analysis of the natural history of locally recurrent breast cancer indicates that the potential for its masking is negligible. Survival curves of patients submitted to immediate breast reconstruction are similar to those reported for historical controls. The ideal candidate for an immediate reconstruction is a stage I (negative axillary nodes) patient. As immediate breast reconstruction does not alter the prognosis of breast cancer patients nor does it harm the use of adjuvant therapies, the authors believe that even a well motivated stage II (positive axillary nodes) patient should be considered as a candidate for an immediate reconstructive procedure. PMID- 2218299 TI - [Professional training in health]. PMID- 2218298 TI - [Lower limb repair. Bipedicled fasciocutaneous flap. A new technical approach]. AB - The authors present an anatomical study of a fasciocutaneous flap of the lower limb and its clinical application. Sixteen patients with loss of cutaneous substance and exposure of the leg bone were operated on. The bipedicled fasciocutaneous flap presented by the authors allows the coverage of large areas of the lower limb in the initial stage of treatment. Preservation of the superficial venous system allows for a better vascularization of the flap and, thus, for the use of larger flaps. PMID- 2218300 TI - [Diagnosis of epilepsy]. PMID- 2218301 TI - [Surgical treatment of inguinal hernias with local anesthesia]. AB - Eighty-four cases of inguinal hernioplasty by Bassini's modified technique were performed using 1% lidocaine in regional infiltration block. The report analyzes the use of local anesthesia in the treatment of inguinal hernias. All patients had small reducible and non-recurrent inguinal hernia. Twenty-six compensated high risk patients were operated in the hospital and dismissed in the second post operative day, whereas the others were operated as outpatients and dismissed two hours after the surgical procedure. The rate of complication was low, but pain was a common complaint. In general, there was a good acceptance of this kind of anesthesia. The authors concluded that local anesthesia is a valuable method for the treatment of inguinal hernia. PMID- 2218302 TI - [Acute jejunogastric intussusception]. AB - The authors present one case of type III jejunogastric intussusception that occurred on the 9th post-gastrectomy day. They compare this case to five others seen at the same hospital in the last nine years. They discuss the rarity of this complication that can only be resolved surgically, the importance of early diagnosis for the favorable clinical evolution, and the surgical technique used. They stress the need to include jejunogastric intussusception in the differential diagnosis of high intestinal obstruction in gastrectomized patients both in the early and in the late post-operative period. PMID- 2218305 TI - Another look at the new state Medicare law. PMID- 2218303 TI - [Late diagnosis of juvenile dermatomyositis with spontaneous pneumothorax, pneumomediastinum, and subcutaneous emphysema]. AB - The authors describe a 11 year-old girl that presented eczematous scabies with acute oligoarthritis that subsided in one day. Fourteen months later, she developed a classical juvenile dermatomyositis with spontaneous pneumothorax, pneumomediastinum, subcutaneous emphysema; pulmonary infection due to Pneumocystis carinii had been diagnosed and was attributable to immunosuppressive therapy. Despite the late diagnosis, the rapid disease activity and the multiple complications, clinical and laboratory controls were achieved by the corticotherapy and by an early diagnosis and treatment of complications. PMID- 2218304 TI - [Familial Bloom's syndrome associated with neuroblastoma]. AB - Bloom's syndrome (BS) is an autosomal recessive disease characterized by short stature, sensitivity to sunlight, and telangiectasic malar erythema. It is associated to chromosomal breakage, to primary combined immunodeficiency, and to a high incidence of neoplasias. The authors report the case of two siblings with BS and associated immunodeficiency. Both patients were male and 5 (A) and 4 (B) years old at the time of diagnosis. Chronic diarrhea, recurrent otitis media, purulent rhinitis, conjunctivitis and pyodermatitis were reported by patient A. Patient B was admitted with diagnosis of bilateral neuroblastoma and had the tumor resected. Later on, he presented with oral moniliasis, herpetic stomatitis, and skin abscesses. This patient did not have recurrent infections. Immunological evaluation showed normal serum levels of CH50, C3, and C4 for both patients. Serum IgG, IgA, IgM, and salivary IgA levels were: 455 mg/dl, 15mg/dl, 20mg/dl, 0.6mg/dl for A, and 400mg/dl, 15mg/dl, 20mg/dl, and 0.2mg/dl for B, respectively. Serum antipolio antibodies (1, 2, and 3) were normal, and low levels of isohemagglutinins were observed in both patients. T cells subset determination showed: patient A--OKT3 = 66%, OKT4 = 33%, OKT8 = 32%, and 4/8 ratio = 1.0; patient B--OKT3 = 70%, OKT4 = 32%, OKT8 = 34%, and 4/8 ratio = 1.0. In vitro cellular immune response to PHA was depressed only in patient B. Patients karyotype showed chromosomal breaks with sister chromatid exchanges. Neither patient had abnormal alphafetoprotein and carcinoembryonic antigen serum levels. The rarity of such associations justifies the presentation of the cases. PMID- 2218306 TI - Reporting physicians' mistakes. PMID- 2218307 TI - Ethical issues in the practice of medicine. PMID- 2218309 TI - "Am I my brother's keeper?": a case study. PMID- 2218308 TI - "I do not want to be resuscitated": a case report. PMID- 2218311 TI - Cesarean section rates in Rhode Island, 1986-1988. PMID- 2218310 TI - Ethical issues at the end of life. PMID- 2218312 TI - The Brown University Program in medicine Class of 1990. PMID- 2218313 TI - Graduate medical education at the Brown University affiliated hospitals and institutions. PMID- 2218314 TI - Cheating in medical school: a problem or an annoyance? PMID- 2218315 TI - An outbreak of staphylococcal food poisoning among East Providence school children. PMID- 2218316 TI - A promising new treatment for hypercalcemia. PMID- 2218318 TI - AIDS claims more and more young women. PMID- 2218317 TI - Corticosteroids delay pneumonia in AIDS patients. PMID- 2218319 TI - Trading places--a seasonal exchange program. PMID- 2218320 TI - To appreciate nurses, try being the patient. PMID- 2218321 TI - How to spot child abuse. PMID- 2218322 TI - Incest: break the silence, break the cycle. PMID- 2218323 TI - Why the nursing shortage may not be all bad. PMID- 2218324 TI - Urokinase: restoring circulation without surgery. PMID- 2218325 TI - Nursing the mind. Understanding schizophrenia. PMID- 2218326 TI - When the patient is out of control. PMID- 2218328 TI - Legally speaking. Who's to blame for faulty equipment? PMID- 2218327 TI - What women can do to protect against osteoporosis. PMID- 2218330 TI - Yet another adverse effect of DES exposure. PMID- 2218329 TI - Home rehab for cardiopulmonary patients. PMID- 2218331 TI - [Detection and treatment of deafness in children]. AB - Deafness must be systematically looked for in children during the first year of life, since the behaviour of a child with impaired hearing may closely resemble that of a child with normal hearing. Severe or deep deafness can be detected at birth by means of a babymeter. Between the ages of 6 and 18 months, sound emitting toy tests enable deafness to be detected. It is only at the age of 2-3 years that testing can be performed separately on each ear to detect unilateral deafness. Treatment varies according to the degree and type of deafness. Conduction deafness is usually due to otitis media serosa and is treated with transtympanic aerators. Perceptive deafness requires acoustic prosthesis associated with orthophony and parental guidance. PMID- 2218332 TI - [The daily life of deaf children]. AB - The loss of hearing modifies in every respect the relations between a child and his environment and results in serious communication problems. An early diagnosis and a coherent management using all the techniques that facilitate communication can thoroughly alter the consequences of deafness. The therapeutic and educative planning must be done by a competent, multidisciplinary team working in close cooperation with the child's parents. The plan must be adjusted to each individual child and constantly readjusted, the target being the social integration of deaf children when they reach adulthood. PMID- 2218333 TI - [Conduction deafness in adults. Diagnostic elements and therapeutic principles]. AB - In the vast majority of cases, conduction deafness is due to a lesion of the eardrum-ossicles system located in the middle ear. The diagnosis, relatively easy, rests on the results of acoumetry (performed with a tuning-fork), audiometry and acoustic impedance measurement. The causes of conduction deafness are multiple and can be divided into 5 categories: major or minor malformations, injuries, tumours, otospongiosis and chronic otitis media. The last two named are the most frequent and must be considered first. Otospongiosis is the most common cause of conduction deafness with healthy typanic membrane. Kophosurgery usually triumphs in this field, even though occasional incidents or accidents must be deplored. Chronic otitis media has different forms and usually succeeds to an inflammatory disease of childhood: serous otitis which is the most obvious common factor in all forms. Despite its apparent complexity, otitis media can be diagnosed by the general practitioner. Although kophosurgery has made remarkable advances, surgical treatment is not always required. PMID- 2218334 TI - [Diagnosis of perceptive deafness in adults]. AB - The finding of perception deafness in an adult patient should set off full clinical and paraclinical evaluation, as this symptom may hide two problems requiring urgent attention. The first problem concerns the diagnosis: any unilateral and progressive perceptive deafness suggests a possible acoustic neurinoma. The second problem is one of therapeutic decision, since in all patients with sudden onset deafness the prognosis depends on an early treatment. General practitioners can use simple tests that will give them some indications on the severity of the loss of hearing, but to establish the side and cause of the deficit, additional and highly specialized examinations are always needed. Medical and hearing aids are sufficient in most patients. Surgery should be reserved to very special cases and will be contemplated or not, depending on the cause of the deafness. PMID- 2218335 TI - [Occupational deafness]. AB - Occupational deafness is usually caused by acoustic traumas and is particularly frequent in developed industrial countries. It proceeds very insidiously and characterized by bilateral perceptive hypoacusis of cochlear origin, centred on the 4000 Hz frequency. The social impairment is obvious and is often accompanied by tinnitus when the weighted mean hearing loss reaches 35/dB on conversation frequencies of 500 to 4000 Hz. The degree of deafness depends on multiple factors such as the physical characteristics of the traumatic noise (the critical level being 90 dBA), the highly variable individual susceptibility, the age of the subject and any previous or concomitant ear disease. In the absence of effective treatment one must rely entirely on prophylactic measures. Dysbaric occupational deafness if increasingly frequent in aeronautical and hyperbaric environments. It is usually of the mixed type, affecting both the middle and the inner ears. Deafness due to a hyperbaric environment figures on the list of occupational diseases. Occupational deafness of toxic origin is exceptional nowadays. PMID- 2218337 TI - [Is obesity hereditary]. PMID- 2218336 TI - [Cochlear implants in 1990]. AB - The various techniques of cochlear implantation are described. Implants may be divided into mono- and multi-electrode and into intra- and extra-cochlear. Cochlear implants are indicated only in patients with total or deep bilateral deafness with residual fibres still functioning in the acoustic nerves. Intra cochlear multi-electrode implants are the most sophisticated ones and usually provide better performances than those observed with mono-electrode implants. PMID- 2218339 TI - [Neurogenic, medullary, cerebellar, myogenic syndrome. Diagnostic orientation and management]. PMID- 2218338 TI - [Oxygen: from transport to consumption. Symposium organized by Lilly-France Laboratory, Paris, September 22, 1989]. PMID- 2218340 TI - [Tetanus. Epidemiology, etiology, physiopathology, diagnosis, development and prognosis, principles of curative, preventive and prophylactic treatment]. PMID- 2218341 TI - [Manic-depressive psychosis. Diagnosis, development and prognosis, principles of treatment]. PMID- 2218342 TI - [Pregnancy toxemia and eclampsia. Diagnosis, course and prognosis, treatment]. PMID- 2218343 TI - [Cancer of the tongue. Etiology, diagnosis, course and prognosis, principles of treatment]. PMID- 2218344 TI - [Pathology of the pleura]. PMID- 2218345 TI - [The mesothelial cells]. AB - Mesothelial cells are described in situ at the surface of the pleura. Their functions are discussed, in relation with the inflammatory response to different agents (infectious agents, mineral fibres...) and with the carcinogenic transformation, particularly in relation to asbestos exposure. The mechanisms of fibrogenesis, either symphysis or pleural plaques, are not clearly understood. The numerous studies now in progress on the different steps and mechanisms of mesothelial transformation and mesothelioma genesis are summarized focusing on the most recent cytogenetic and molecular biology findings. PMID- 2218346 TI - [Diagnosis of pleurisy]. AB - Nowadays, the diagnosis of pleural effusion is greatly facilitated by thoracoscopy. Since most pleural effusions are due to neoplasias (notably in patients older than 40 years) and since the prognostic value of an early diagnosis is obvious in case of pleural carcinoma (notably mesothelioma), there is no justification in allowing the effusion to become chronic. If the diagnosis is confirmed by needle biopsy, thoracoscopy can rapidly be performed by skilled operators: in 95 p. 100 of the cases it provides the diagnosis. Five per cent of pleural effusions remain of unknown origin. In such cases the patients must be closely followed up for 12 to 18 months to make sure that no cancer has been missed and another thoracoscopy must be performed at the slightest clinical change. Test treatments (antibuberculous drugs, corticosteroids) are now obsolete. PMID- 2218348 TI - [Epidemiology and etiology of mesothelioma]. AB - The early diagnosis of mesothelioma rests on very common clinical evidence, including pleuritis of recent onset, history of contact with asbestos chest pain, often moderate loss of weight and slight changes in old pleural images. The sensitivity of formal diagnostic examinations is 23 p. 100 for pleural fluid cytology, 24 p. 100 Adams' needle biopsy and 93 p. 100 for thoracoscopy, where the only negative results are obtained in patients with adhesive pleuritis. Prognosis depends on several factors, the most favourable ones being the histological type of the lesion (epithelial or mixed), the fact that it is limited to the parietal or diaphragmatic pleura and, on the patient's side and accessorily: female sex, lack of exposure to asbestos, age under 50, good general condition and absence of chest pain. PMID- 2218347 TI - [Tumoral markers and monoclonal antibodies]. AB - The frequency of malignant pleuritis in general practice and its often difficult diagnosis have led to the ever increasing use of tumoral markers (TMs) which may overcome these difficulties and of immunocytochemical methods which may improve the results obtained by routine cytology. TMs are used in the diagnosis: a) to detect false-negative results and sometimes exclude false-positive results of cytology ("reactive" mesothelial cells); b) to distinguish reliably between malignant mesothelioma and metastatic pleuritis from an undetected adenocarcinoma, and c) to provide additional information, if needed, on the nature and origin of a malignant pleuritis. In pleural carcinology, TMs can be used as part of various methods which may be biochemical (assays of the marker in serum and, more important, in pleural fluid), cytochemical or immunocytochemical, histochemical or immunohistochemical, cytogenetic and cytofluorimetric. TMs can be defined and classified as follows: 1) intrinsic tumoral cell abnormalities; 2) substances associated with tumours which either induce them in the body without any specificity or secrete first generation TMs such as CEA, hyaluronic acid, NSE, ect.; 3) tumour-related antigens recognized by monoclonal antibodies or second generation markers. These markers, extremely varied, are directed against cell and often cell membrane antigens. They are not always very specific. When assayed separately their diagnostic sensitivity is low, but when used in batteries and combined with routine cytology they may fulfill the objectives listed above and fairly significantly improve the results of cytology. As last resort, they can be used in immunomorphology on cytology or biopsy specimens and provide a decisive answer. PMID- 2218350 TI - [Treatment of pleural tumors]. AB - There is no such thing as a standard treatment for diffuse malignant mesothelioma of the pleura (DMM). Surgery, radiotherapy or chemotherapy do not appear to modify the course of the disease, and there seems to be little chance of DDM of the pleural being cured, except for those rare cases of stage I tumour detected early on and curable by surgery or by intrapleural interferon. Biological response modifiers, such as interferon or interleukin, might well be the future therapeutic approach of a tumour known for its resistance to chemotherapy. Surgery remains effective in localized benign (fibroma) or malignant (fibrosarcoma) tumours, although fibrosarcoma has a tendency to local recurrence. Metastatic pleuritis has no other treatment than that of the primary cancer. PMID- 2218349 TI - [Diagnosis and prognosis of malignant mesothelioma]. AB - The early diagnosis of mesothelioma rests on very common clinical evidence, including pleuritis of recent onset, history of contact with asbestos, chest pain, often moderate loss of weight and slight changes in old pleural fluid cytology, 24% for Adams' needle biopsy and 93% for thoracoscopy, where the only negative results are obtained in patients with adhesive pleuritis. Prognosis depends on several factors, the most favourable ones being the histological type of the lesion (epithelial or mixed), the fact that it is limited to the parietal or diaphragmatic pleural and, on the patient's side and accessorily: female sex, lack of exposure to asbestos, age under 50, good general condition and absence of chest pain. PMID- 2218351 TI - [Pleurodesis technics]. AB - In patients with recurrent malignant or benign pleural effusion practitioners use specific treatments, but they are then faced with the problem of pleural fluid recurrence. Several techniques of pleurodesis have been used, including drainage, surgery, intrapleural injections and poudrage. From an analysis of the results obtained and from our own experience, we have come to the conclusion that poudrage under thoracoscopy is the best type of pleurodesis. PMID- 2218352 TI - [Transgenic mice as models for human diseases]. PMID- 2218354 TI - [Eosinophilia today]. PMID- 2218353 TI - [Adrenoleukodystrophy: a new case of familial adrenal insufficiency]. PMID- 2218355 TI - [Red eye. Diagnostic orientation and management]. PMID- 2218356 TI - [Uncomplicated cholelithiasis. Etiology, physiopathology, diagnosis, medical treatment and principles of surgical treatment]. PMID- 2218357 TI - [Virus infections: herpes simplex. Epidemiology, physiopathology, diagnosis, evolution and prognosis]. PMID- 2218358 TI - [Louis Justin-Besancon. 3 June 1901 - 26 December 1989]. PMID- 2218359 TI - [Evaluation of knee radiograms as criterion of femoro-tibial gonarthrosis development]. AB - Within the context of the initiation of practising rheumatologists to the methodology and management of clinical trials, it seemed opportune to carry out a clinical research study whose aim would be pedagogical as well as scientific: pedagogical by making them aware of the problems linked with the management of a clinical trial and the problem of the variability of the measurements; scientific by trying to appreciate the clinical significance of the radiological examination data in the course of femoro-tibial gonarthrosis. The patients suffering from femoro-tibial gonarthrosis corresponding to the ARA criteria and having given their consent have been included in a multicentric prospective study where each investigator had to record--apart from the patient inclusion criteria--his personal characteristics, the characteristics of the arthrositic disease (site, aetiology, history, clinical condition). Moreover, the radiological analysis of a recent, frontal photograph of the knee on charge has been carried out by a practising rheumatologist and by a university-hospital rheumatologist. The number of observations collected (879), the low percentage of non exploitable data (3.4%) are in favour of having clinical research studies carried out by practising rheumatologists. The analysis of the study shows the following: 1) the inter-observer variability of the reading of the photograph of the gonarthrosis is high outside three parameters (osteophyte, degree of pinch and height of the spacing measured in millimetres) with an interclass correlation coefficient of 0.69, 0.71 and 0.69 respectively; 2) the radiographical examination data correlate only very partially with the clinical elements of the disease. PMID- 2218361 TI - [Role and place of MRI in the diagnosis of aseptic osteonecrosis of the femoral head. Apropos of 58 pathologic hips]. AB - The early diagnosis of aseptic osteonecrosis of the femoral head has always been difficult. By studying 58 cases, the authors have demonstrated the diagnostic superiority of magnetic resonance imaging. As in the literature, we found aseptic osteonecrosis of the femoral head with no clinical sign, neither radiographic nor scintigraphic, by positive magnetic, resonance imaging. Moreover, it enables the simultaneous study of both hips. It gives with precision the age and extent of the necrosed fragment and enables an absolute differential diagnosis with hip algodystrophy. Magnetic resonance imaging is therefore the second and only examination to be carried out after the standard radiography. The couple, radiography and magnetic resonance imaging, gives all the necessary information for the diagnosis and classification of the aseptic osteonecrosis of the femoral head and Te 99m bone scintigraphy and scanner, whose value was limited, can thus be avoided. PMID- 2218360 TI - [Cruralgia. Frequency of foraminal hernias not to be operated. Retrospective study of 19 cases]. AB - The authors report the observation of 19 patients suffering from cruralgia, who have undergone a tomodensitometric examination. A foraminal hernia was revealed in 13 patients. Four other patients presented an arthrositic or hyperostositic foraminal stenosis. Only one patient was operated upon. PMID- 2218362 TI - [Hypertrophic osteoarthropathy and liver graft rejection. Apropos of 2 cases]. PMID- 2218363 TI - [Synovial cysts of psoas bursa in men. 4 cases and literature review]. AB - The authors report four observations of synovial cysts of the psoas bursa. They recall the following from a review of the literature: the relative rarity of these lesions, their physiopathology, their clinical expression, the diagnostic tests available, which at present consist mainly of modern imaging (echography and tomodensitometry), and finally the principles of treatment. PMID- 2218364 TI - [Pathologic fracture disclosing Letterer-Siwe disease in adults]. PMID- 2218365 TI - [The value of nuclear magnetic resonance in tuberculosis of the posterior vertebral arch. A case report]. PMID- 2218367 TI - [Rhizomelic pseudopolyarthritis disclosing cancer of the cavum. A case report]. PMID- 2218368 TI - [Melitococcal pseudo-Pott with abscess of the psoas]. PMID- 2218366 TI - [Horton's disease disclosed or caused by skull trauma]. PMID- 2218369 TI - [Lupus erythematosus disseminatus and atrophic polychondritis]. PMID- 2218370 TI - [Epidemiologies or epidemiology?]. PMID- 2218371 TI - The relationships between selected anthropometric and socio-economic data in schoolchildren from different social strata in Rio de Janeiro, Brazil. AB - The nutritional status according to anthropometric data was assessed in 756 schoolchildren from 5 low-income state schools and in one private school in the same part of Rio de Janeiro, Brazil. The prevalence of stunting and wasting (cut off point: less than 90% ht/age and less than 80% wt/ht) ranged in the public schools from 6.2 to 15.2% and 3.3 to 24.0%, respectively, whereas the figures for the private school were 2.3 and 3.5%, respectively. Much more obesity was found in the private school (18.0%) than in the state schools (0.8-6.2%). Nutritional problems seem to develop more severely in accordance with the increasing age of the children. Therefore it appears advisable to assess schoolchildren within the context of nutritional surveillance system. PMID- 2218372 TI - An investigation into support for restrictions on HIV carriers in the Chicago metropolitan area. AB - An investigation into support for restrictions on people testing seropositive for HIV is reported on. Data were collected during telephone interviews with two hundred adults aged eighteen to sixty-five in the Chicago metropolitan area. Using the analytic technique of LISREL, six models which attempt to explain support for restrictions were tested. It was found that the model best supported by the data indicates that two groups contribute to support for restrictions on HIV carriers--one due to intolerance of homosexuality and one to mistrust of public health officials regarding their control and management of the AIDS epidemic. The relevance of these findings for public health policy makers is discussed. PMID- 2218373 TI - [The School of Public Health at the University of Sao Paulo]. PMID- 2218374 TI - [Acute poisoning by aldrin: relationship between serum levels and toxic effects in humans]. AB - In the attempt to correlate clinical findings with serum levels of aldrin, sixteen patients were followed-up after acute intoxication by this agent. Eight of them, males and females, aged from 1 to 37 years, presented no or light symptoms (some discomfort and nausea). The serum of one of these patients was found to contain 16.6 ppb of aldrin and that of another, 1.41 ppb of dieldrin. A group of five patients, aged from two to 30 years, showed symptoms of moderate severity, reporting nausea, vomiting, drowsiness, dyspnea, sweating, mild jerking, rise in blood pressure and convulsions. Of these cases, two were accidental and three were attempted suicides, the majority achieving complete recovery within 24 hours. Serum levels of aldrin were between 6.98 ppb and 26.3 ppb and of dieldrin between 82.00 and 314.18 ppb. We found three severe cases, aged from 21 to 35 years, two attempted suicides and one occupational case. Two of these patients died and one of them presented hypothermia, coma, absence of reflexes and generalized convulsions, and another presented abdominal pain, paleness, sweating, cold extremities, dyspnea, hyperthermia and generalized convulsions. In the first one that died the serum levels were: of aldrin 30.00 ppb and of dieldrin 720 ppb. In the other levels of 747.3 ppb of aldrin and 1,314.00 ppb of dieldrin were found. The third had less serious symptoms and presented serum levels of aldrin of 31.05 ppb and of dieldrin 147.11 ppb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218375 TI - [Plasma zinc levels and the anthropometry of children in the outskirts of urban centers in Brazil]. AB - The main objective of the present study was to estimate plasma zinc concentration in children belonging to low-income families residing in three different neighborhoods on the outskirts of Ribeirao Preto, SP, Brazil, and to determine a possible correlation of this parameter with several anthropometric measurements. Plasma zinc levels were lower than 70 micrograms% in 13% of the children studied. Weight for age, height for age and weight/height ratio were below 90% of the 50th percentile of National Center for Health Statistics (NCHS) in 42.9%, 6.3% and 9.5% of children, respectively. Tricipital fold, arm circumference and muscle circumference were also below 90% of the 50th percentile in 65.8%, 11.0% and 7.3% of the children, respectively. No correlation was observed between plasma zinc levels and the anthropometric parameters studied. PMID- 2218376 TI - [Photosensitivity and stability of freeze-dried and/or reconstituted measles vaccines (Biken CAM-70 strain)]. AB - Three different lots of measles vaccines produced with the Biken CAM-70 virus strain were requested from the central cold store of the Public Health Department of the State of S. Paulo, Brazil, and assays on photosensitivity at 2-8 degrees C, and on stability at 28, 36.5 and 45 degrees C were carried out to find out for how long these vaccines would maintain their minimum potency, established as being 3.70 log10 or 5000 TCID50 (50% tissue culture infective dose) per human dose. The analysis of the adjusted straight regression lines indicated that, with the passage of time, the potency of lyophilized or reconstituted vaccines, as well as of vaccines exposed to or protected from light decreased. Light-exposed vaccines, however, became less potent than vaccines protected from the light. None of the vaccine lots studied, reconstituted and stored at 2-8 degrees C, exhibited homogeneity as to sensitivity to light. When freeze-dried vaccines had their photosensitivity studied at 2-8 degrees C, lots 1 and 2 presented greater thermal degradation when exposed to light than when protected from it. However, in both instances, it was found that potency fell below that taken as minimum for the Biken CAM-70 virus strain. At all other temperatures considered, even when protected from light, lots 1 and 2 did not retain the minimum potency. Lot 3 kept the expected stability for 60 days at 2-8 degrees C when protected from light and for 40 days when unprotected, but its thermal degradation at other temperatures was more intense (28 degrees C: 5 days; 36.5 degrees C: 2 days; 45 degrees C: 0.5 day).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218377 TI - [Analysis of the use of an ambulatory unit of the Department of Health of the city of Sao Paulo, SP (Brazil)]. AB - A working proposal for the integration of the activities of public health assistance is presented. Two health clinics in the city of S. Paulo, Brazil, were studied. Taking as a starting-point that all activity in the health sector depends on community participation, this study sought to discover how the population has received and used the geographically integrated health services. For this purpose, information was collected from the users of both of these services, by means of a questionnaire, as to the motive for the use of the service, the service's ability to meet the need, the degree of user-satisfaction, etc. The analysis of the above information as well as of the objective and the working method of these services, leads to the conclusion that they are used by the public in a selective way for the purpose of meeting immediate needs related to present illnesses. PMID- 2218378 TI - [An intra-community profile of nutritional deficiency: a study of children under 5 years of age in a low-income community in Rio de Janeiro (Brazil)]. AB - This study is part of a larger epidemiological study concerned with the health status of children under the age of five carried out in the squatter settlement of Rocinha, and focuses on the nutritional profile of a representative sample of 591 children. According to the weight-for-age criteria (Gomez's classification), 23.9% and 2.0% were, respectively, mildly and moderately malnourished. This finding is in agreement with the assessment using weight-for-height and height for-age as anthropometric indicators: (a) absence of acute malnutrition (wasting) indicated by a pattern overlapping that of an expected normal population, and (b) growth deficiency (stunting) indicated by 7% and 15% of children exceeding the proportion normally expected to be, respectively, below the -1 and -2 standard deviate limits. So far as growth failure was concerned, the following variables remained associated even when controlling for economic status (indicated by the environmental conditions of the household): low birth weight, number of siblings equal to or above three, male gender, a history of never having breastfed and a family history of previous sibling death. Each variable is discussed separately, as well as the overall nutritional profile and the marked social intra-community stratification related to growth deficit. PMID- 2218379 TI - [Birth weight and patterns of delivery care in a municipality of Sao Paulo State, Brazil, 1986]. AB - A survey was made of the birthweight of live births and delivery care at hospitals in the city of Araraquara, S. Paulo State, Brazil, in 4,776 newborn infants during 1986. The incidence of cesarean delivery was 76.0%. It was discovered that the proportion of cesarean delivery was higher for deliveries with private medical care (92.4%) than for deliveries with free assistance (44.0%). The incidence of low birthweight was of 9.2%. The highest proportion was found in patients with free medical assistance and was of 10.8%, that of social security patients being at an intermediate level (9.8%) and of private patients at 5.6%. PMID- 2218380 TI - [The French College of Oral Medicine. History and peripety]. PMID- 2218381 TI - [Labioglossopexy in Pierre Robin syndrome. Our experiences apropos of 70 cases]. AB - Pierre Robin syndrome is typically characterized by glossoptosis and retrognathia associated with cleft palate, respiratory and deglutition disturbances. Two morphological tendencies arise out of this 70-patient series, 50 of whom were managed with the same therapeutical regimen, which included labioglossopexy and was associated with only one case of death: "deforming" type Pierre Robin syndrome most commonly follows a favorable course with respect to both function and facial deformations, provided labioglossopexy is carried out sufficiently early. Indeed, this surgical operation allows for prompt restoration of normal function, thereby limiting the dysfunction-deformation vicious circle. This form of Pierre Robin syndrome may find its origin in the embryo's abnormal amniotic environment. "Malformation"-associated Pierre Robin syndrome often presents with combined anomalies, respiratory disturbances that may evolve into severe airway problems, impaired deglutition and abnormal brain development; in most cases, labioglossopexy will dramatically improve the immediate state of the child, although long-term prognosis as regards malformation is rather guarded. PMID- 2218382 TI - [Control of the incisor axis in the vestibulo-lingual direction using an original titanium-molybdenum alloy arch]. AB - In order to restore the vestibulo-lingual orientation of the incisor axis while controlling the position of the crowns, the author suggests using a simple original arch, compatible with any of the multi-clip technics used by orthodontists. This arch is made of Titanium-Molybdenum Alloy and presents the distinctive feature of being specially shaped, on the ribbon side, so as to be introduced edgewise. Practical ease, efficiency in obtaining large amplitude, precisely controlled movements, as well as accurate measurement of torque make of this instrument a practical tool for controlling the incisor axis in the vestibulo-lingual orientation, and for improving the I/i angle warranteeing the stability of the results. This arch can be used both in monodisciplinary and multidisciplinary orthodontics, more particularly in surgical-orthodontic management of retrognathia combined with traumatic supraclusion of incisors or with linguoversions of central upper teeth. PMID- 2218383 TI - [Cancellous mandibular autografts and titanium mesh]. AB - Pure cancellous bone transplants constitute an alternative to the usual cortico cancellous grafts used in certain cases for restoring interrupting substance loss (ISL) in the mandible. The greater number of surviving transplant cells, the rapid revascularization and more complete osteogenesis that are achieved cause indications for this type of graft to be particularly well adapted for cases where local repair conditions are precarious, such as bullet wound related sequelae. Indications for their utilization also extend to patient who have had benign tumors excised. The titanium-made receiving splint designed by Pr. Dumbach is particularly well adapted to this type of restoration; it provides for necessary functional stresses to be translated to the implant, allowing for the latter's incorporation, while controlling the direction of osteogenesis, thereby yielding excellent morphological and functional results. PMID- 2218384 TI - [The importance of avoiding the use of rigid fixation in functional genioplasty]. AB - This article presents a brief review of several principles which Delaire has shown to be important in both craniofacial growth and cranio-maxillofacial balance. In light of these events, we propose that the maxillofacial surgeon either avoids, if possible, the use of rigid fixation in functional genioplasty or that he removes the screws and plate at a later date. The specific patterns of bone apposition and resorption observed following functional genioplasty form the basis for this recommendation. PMID- 2218385 TI - [Skin carcinoma of the face: surgery or radiotherapy?]. AB - Surgical exeresis and radiation therapy are effective means of treatment for facial carcinomas. In some areas that are difficult to manage (nose, ears, periorbital region), the respective importance of both approaches is discussed. We report on the retrospective study of 309 patients seen after a skin carcinology consultation in which a dermatologist, a surgeon and a radiotherapist were associated. These 309 patients, with a mean age of 73 years, presented with 375 carcinomas, i.e. 246 basal-cell (BC) and 119 epidermoid (EC) carcinomas. The most frequent sites were the nose (33.8% of BC), the inner canthus (12.7% of BC), the lower lip (23.8% of EC) and the ear (15.6% of EC). Management mainly consisted of surgery (50.8%) then Curie therapy (37%). The rate of recurrence was the same (10.5%) after surgery and radiation therapy. The study of the results leads us to advocating surgery for carcinomas of the ear (due to the occurrence of radiation necrosis in every third case after radiation therapy) and Curie therapy for carcinomas of the lower lid (except the inner canthus) because of recurrence in every second case treated with surgery. We currently prefer surgery for carcinomas of the lower lip (radiodermatitis in 11.8% of cases) and Curie therapy for the nose (lower rate of recurrence than with surgery). However, in the last two cases, the proposals for treatment should be confirmed by randomized studies. Thus facial carcinomas of the skin surrounding the orifices of the face and/or those that affect patients who are difficult to treat must be seen during a skin carcinology consultation by a dermatologist, a surgeon and a radiotherapist working together.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218386 TI - [Fibrous dysplasia of the jaw. Therapeutic approach apropos of 12 cases]. AB - Twelve cases of maxillo-facial fibrous dysplasia are presented, with a brief review of the condition. Only the complete excision of the lesion allows full healing, but it is rarely feasible, even with immediate reconstruction. The surgical abstention and partial excision keep many indications, but require a regular follow-up. PMID- 2218387 TI - [Necrotizing fasciitis of the face. Clinical and therapeutic aspects]. AB - Necrotizing fasciitis is a synergic infection, the chief causal agents of which are beta-hemolytic group A streptococci. The authors insistingly review the different aspects of this rare affection and stress the importance of emergent medical and surgical management, as the evolution of the disease is still often lethal. PMID- 2218388 TI - [Myxoma of the nerve sheath. Apropos of a case]. AB - A case of oral nerve sheath myxoma is presented with the findings of light microscopy and immunochemistry. The tumor consists of well-defined lobules which are separated by septa composed of fibrous connective tissue that reassembled the perineurium. Each lobule is composed of elongated and stellate cells in a basophilic mucoid matrix. Immunohistochemically, S-100 protein is strongly positive in all tumor cells. The histogenesis and differential diagnosis are discussed. PMID- 2218389 TI - [Cystic cervicofacial lymphangioma]. AB - A review of fifteen new cases of cystic cervicofacial lymphangiomas is presented. While discussing the different localizations of these malformations, the authors emphasize the relationships existing between this type of malformation and both the facial nerve and the vasculonervous axis of the neck. They recommend surgical management. 1-to-10 years' follow-up revealed one case of local recurrence associated with incomplete excision. PMID- 2218390 TI - [Occult tumors of the parotid gland and facial paralysis. A diagnostic problem]. AB - The facial palsy produced by a parotid tumour, could be misdiagnosed due to the absence of a palpable mass or other any signs in the computerized axial tomography or nuclear magnetic resonance. However there are data derived from the facial anatomy, course and clinical characteristics from the palsy that could make us thinking on the presence of a parotid tumour. The objective of this article is to present this characteristics, together with a serial of clinic cases which coursed in the beginning with a facial palsy and had problems in their diagnostic. It's also remarked the significance of the presence or not of perineural infiltration to the parotid tumours that will condition not only the prognosis but also the clinic course. PMID- 2218391 TI - [The unforeseen aspects of expertise or the proper use of ones's nose and lips]. AB - On the basis of two expert evaluations, the author first sets out a few general principles needed to guide the expert during his mission. He then describes the peculiar features of the two examples chosen, both of which, in his opinion, justify a valuation far exceeding the standard compensation for the damage sustained by the victims, due to their occupation: one is a customs officer in a major international airport, the other is a trumpeter in a famous philharmonic orchestra. As a conclusion, the author emphasizes the necessity to thoroughly examine any wounded or ill patient prior to deciding to operate them. PMID- 2218392 TI - Pepsinogen release and acid secretion from human and guinea pig gastric mucosa compromised by hypoxia, endotoxin, or critical illness. AB - Despite blockade and neutralization of gastric acid, acute gastric lesions cause substantial morbidity and mortality in critically ill patients. Pepsinogen release in response to noxious stimuli such as hypoxia and endotoxin might contribute to mucosal damage. Guinea pig fundic mucosa was mounted in Ussing chambers. Acid secretion, pepsinogen release, potential difference (PD), and resistance were monitored. Gassing with room air or nitrogen diminished acid secretion and PD but increased pepsinogen release 9.7- and 15.5-fold, respectively (both p less than 0.001). Similarly, endotoxin (0.01 and 0.1 units/ml) dose-dependently inhibited acid secretion and PD but increased pepsinogen release 3.3- and 6.1-fold (both p less than 0.05). Endotoxic and air gassed tissues were edematous with scattered cellular damage by light and transmission electron microscopy; nitrogen-exposed membranes appeared necrotic. Pepsin release may therefore have resulted from cell damage rather than exocytosis. Intragastric peptic activity in critically ill H2-receptor-blocked patients (n = 20) was 5490 +/- 1701 U/ml. The gastric juice of H2-blocked convalescing surgical patients (n = 20) contained 315 +/- 101 U/ml (p less than 0.0001). Occult blood correlated with intragastric peptic activity (r = 0.59, p less than 0.0001) but not with gastric pH (r = 0.04, p = 0.6). These data suggest that the complex of pathophysiologic abnormalities common in critical illness causes substantial pepsin release. Efflux of this potent mucolytic barrier breaker may damage gastric mucosa in severely stressed patients. PMID- 2218393 TI - Primary malignant non-epithelial tumours of the thoracic oesophagus and cardia in a 25-year surgical material. AB - During 25 years, 708 patients with primary malignant tumours of the thoracic oesophagus (n = 376) or cardia (n = 332) were referred to our department. Two hundred and forty-nine patients had squamous cell carcinoma and 425 adenocarcinoma. The other 34 tumours, which were primarily classified as undifferentiated carcinoma, malignant carcinoid or non-epithelial, were re evaluated by means of a second microscopic histologic examination and immunohistologic investigation. This showed primary malignant non-epithelial tumours in seven patients (0.99%): two malignant melanomas, one leiomyosarcoma, one malignant fibrous histiocytoma in the oesophagus (1.06%), two malignant lymphomas, and one malignant melanoma in the cardia (0.90%). All but two of the patients with non-epithelial malignant tumours were 67 years of age or older, and oesophagogastrectomy was performed in all. All tumours were 5 cm or more in diameter (median, 8 cm). Distant metastases were found in three cases. Five died of postoperative complications, one of cancer recurrence 7 months after the operation, and one of an unrelated cause without cancer recurrence 16 months postoperatively. Except for two of the melanomas, the diagnosis was not established until histologic examination of the surgical specimen was performed and, for the third melanoma and the malignant fibrous histiocytoma, not until the present re-evaluation. The characteristics of these seven tumours are discussed, and the importance of obtaining a correct diagnosis from endoscopic biopsy specimens is emphasized. PMID- 2218394 TI - Regional differences in peripheral circulation between upper and lower extremity in patients with cirrhosis. AB - In 42 patients with compensated cirrhosis and 31 control subjects, blood flow (BF) and vascular resistance (VR) were measured at the forearm and calf, using a pneumoplethysmograph. In some of the subjects deep-body temperature (DBT) was also measured by the zero heat flow method. In cirrhosis, BF and DBT were significantly higher and VR was significantly lower in the forearm than in the calf. Corresponding differences were not observed in control subjects. When these indices of the forearm were compared between cirrhosis and controls, BF and DBT were significantly higher and VR was significantly lower in cirrhosis than in controls. In cirrhotics in whom the gradient between forearm BF and calf BF was 1 ml.dl-1.min-1 or more (forearm greater than calf), the vascular response of the forearm to cold stimulation was reduced, whereas in the remaining patients and in controls the forearm BF and VR responded significantly. These results suggest that there is a regional difference in peripheral circulation in cirrhotics, partly with participation of impaired sympathetic nervous activity, which may account for the selective distribution observed in the clinical manifestations of vascular spider, palmar erythema, and warm hand, inclined toward the upper extremities or the upper part of the body. PMID- 2218395 TI - The incidence of ulcerative colitis in Northern Norway from 1983 to 1986. The Northern Norwegian Gastroenterology Society. AB - In a 3-year prospective epidemiologic multicentre study in Northern Norway the average annual incidence of ulcerative colitis was 12.8 per 100,000. Both inpatients and outpatients were included. There was a significant sex difference in annual incidence in the health region (15.1 per 100,000 in males versus 10.4 per 100,000 in females), which was most pronounced Nordland county (16.6 per 100,000 in males versus 10.4 per 100,000 in females). The highest incidence was seen in the age group 20-29 years, with an incidence of 30.3 in men and 20.3 in women per 100,000 per year. A family history of first-degree relatives with inflammatory bowel disease was obtained in 10.1%. The pathologic changes were equally distributed among the rectum and the distal and total colon. Ulcerative colitis located to the distal colon seemed more associated with extraintestinal manifestations. PMID- 2218396 TI - Calcium absorption and bone mineral content in patients subjected to ileal bypass because of familial hypercholesterolaemia. AB - Calcium absorption and bone mineral content were studied prospectively in 30 patients with familial hypercholesterolaemia subjected to partial ileal bypass surgery. One-third of the patients were followed up for 10 years after the operation. Six months postoperatively calcium absorption decreased significantly, from a median of 16% to 13%. The effect persisted up to 5 years of follow-up study. Ten years after the operation the absorption of calcium (median, 14.5%) was not significantly different from the preoperative calcium absorption (median, 16%). Bone mineral content, measured in 76% of the patients, was retained in all patients studied. A significant correlation was present between calcium absorption and urinary calcium. The reduction in calcium absorption did not correlate with increases in faecal fat. Other long-term side effects were persistent diarrhoea and moderate steatorrhoea. A significant weight loss was slowly regained in most patients. An increase of renal oxalate excretion was only small and transient in most patients. The study shows that bypass of the terminal 200 cm of ileum for familial hypercholesterolaemia causes moderate diarrhoea and steatorrhoea in most patients but only a slight reduction of intestinal calcium absorption and apparently no risk of bone demineralization. A benefit of a postoperative calcium and vitamin D supply cannot be excluded. PMID- 2218397 TI - Fat inhibits pentagastrin-stimulated acid secretion from the duodenum but not from the proximal jejunum in chronic gastric fistula rats. AB - The effect of fat emulsion in the upper intestine on the maximal gastric acid response to pentagastrin was studied in chronic gastric fistula (GF) rats with a 4-cm blind loop of the duodenum anastomosed to the jejunum (Roux-en-Y). Fat emulsion in the loop inhibited the acid response by 85%. To localize the site of the inhibitory mechanism, GF rats were provided with Thirty-Vella loops of the duodenum (bile and pancreatic ducts transplanted to the proximal jejunum) or with Thirty-Vella loops of the proximal jejunum and a Roux-en-Y loop of the duodenum to prevent gastric juice from entering the duodenum. Perfusion of the duodenal loop with fat emulsion mixed with bile and pancreatic juice reduced the acid response by 49%, but perfusion of the proximal jejunal loop did not alter the response. It is concluded that the intestinal mechanism for inhibition of acid secretion by fat is located in the duodenum in rats. PMID- 2218398 TI - Gastrin in non-neoplastic pancreatic tissue from patients with and without gastrinomas. AB - Processing-independent radioimmunoanalysis for progastrin showed that extracts of normal pancreatic tissue from normal subjects (n = 5) and from patients with adenocarcinoma of the papilla of Vater (n = 4) contain progastrin and its products. The concentrations varied from 0.1 to 5.8 pmol/g tissue, of which carboxyamidated bioactive gastrins constituted 0.03-1.9 pmol/g. In histologically normal and nonneoplastic pancreatic tissue from patients with duodenal (n = 3) and pancreatic (n = 2) gastrinomas the expression of gastrin was significantly higher-14.5 pmol/g (median), of which 28% was bioactive amidated gastrins. Gastrin-17 was the main bioactive product, but its immediate precursor, glycine extended gastrin-17, constituted the predominant part of the preprogastrin product in pancreatic tissue. Proper gastrinoma tissue contained several precursor forms, including intact unprocessed progastrin. Progastrins were also found in high concentrations in plasma from the gastrinoma patients. The results raise the possibility that increased expression of progastrin and its products in non-neoplastic pancreatic tissue is a primary defect predisposing to neoplasia. PMID- 2218399 TI - Phospholipase A2 activity and concentration in several body fluids in patients with acute pancreatitis. AB - According to recent studies, phospholipase A2 (PLA2) may be an important factor in the pathogenesis and pathophysiology of acute pancreatitis. Increased serum PLA2 activities and concentrations have been measured in patients with acute pancreatitis. Serum PLA2 activities have been shown to correlate with the severity and prognosis of the disease. To study the different methods of PLA2 determination, we measured the PLA2 activity by means of an isotopic assay method and the concentration by a radioimmunologic method in several body fluids of 52 consecutive patients with acute pancreatitis. PLA2 activity and concentration were detected in all of the patient body fluids. The serum PLA2 activities were 2.5-fold higher (mean +/- SD, 7.6 +/- 6.0) than normal activities, and the concentrations were 9.6-fold higher (mean +/- SD, 41 +/- 88). The enzyme activities and concentrations correlated well in ascites, fluids from the pleural cavity, and peritoneal lavation and poorly in serum, urine, and fluid from pancreatic pseudocyst. PMID- 2218400 TI - Is gluten challenge necessary for the diagnosis of coeliac disease in young children? AB - Sixty-seven children under 2 years of age presenting with a classic clinical picture of coeliac disease with a severe small-intestinal mucosal lesion were investigated. All improved clinically and histologically on a gluten-free diet. During gluten challenge the mucosal damage recurred in 64 (95.5%) children, thus fulfilling the criteria for coeliac disease formulated by the European Society for Paediatric Gastroenterology and Nutrition. Three (4.5%) children had no mucosal relapse 2 years or more after return to a gluten-containing diet. These children were classified as having transient gluten intolerance. The low frequency of non-relapsers in the present study calls into question the practice of performing gluten challenge. PMID- 2218402 TI - Hepatitis delta virus superinfection among patients with chronic hepatitis B in southern Taiwan. AB - To study the prevalence of hepatitis delta virus (HDV) superinfection among patients with chronic hepatitis in southern Taiwan, total and IgM anti-delta antibody (anti-HD) and delta antigen (HDAg) were determined in 85 histology proven patients with chronic hepatitis. There were 12/85 (14.1%) cases with total anti-HD; 3 of them were also positive for IgM anti-HD. Another 9 (10.6%) cases were positive for HDAg. Thus, the prevalence of HDV superinfection was 21/85 (24.7%), which was significantly higher than previous reports in southern Taiwan. The difference was not seen if anti-HD was used as the only detector. It is concluded that, when other methods are used than previously, HDV infection is more common than previously thought and there is no difference between different parts of Taiwan. PMID- 2218401 TI - A 10-year survey of clinically significant blood culture isolates and antibiotic susceptibilities from adult patients with hematological diseases at a major Swedish hospital. AB - In patients treated with cytotoxic drugs granulocytopenia and septicemia are commonly seen. In this 10-year survey 324 blood culture isolates from 184 patients with hematological diseases and septicemia were studied. The distribution of microbiological diagnoses in patients with hematological diseases as well as acute leukemia 1980-1986 was significantly different (p less than 0.01) from an unselected blood culture material from the same period. The differences are mainly seen between Enterobacteriaceae other than Escherichia coli, Pseudomonas aeruginosa and staphylococci. The microbiological spectrum for patients with hematological disease 1987-1989 was also significantly different (p less than 0.05) from the spectrum of the same group of patients 1980-1986 due to higher frequencies of coagulase-negative staphylococci and alpha-streptococci and lower frequency of E. coli in the latter period. 40% of the isolates were gram positive cocci during the first period and increased to 50% during the second period. The susceptibility testing indicates that trimethoprim/sulfonamide is not as good a choice as ciprofloxacin or norfloxacin for oral antibiotic prophylaxis. For intravenous therapy imipenem/cilastatin or the combinations of an aminoglycoside/piperacillin or aminoglycoside/third generation cephalosporin have advantages over aminoglycoside/trimethoprim/sulfa in combination. However, addition of isoxazolylpenicillin or vancomycin now seems necessary to cover the increasing part of gram-positive bacteria causing septicemia in patients with hematological disease. PMID- 2218403 TI - Incubation time of AIDS: progression of disease in a cohort of HIV-infected homo- and bisexual men with known dates of infection. AB - The time from infection with HIV to symptoms and AIDS is an important parameter in describing the natural course of HIV infection. We here describe disease progression in a group of 389 homo- and bisexual men. Of these 102 had known dates of infection, and during an average follow-up time of 31 months (range 2 108), 28 of these progressed from being symptom-free (CDC group II and III) to having some symptom from CDC group IV; 7 progressed to AIDS. By life-table analysis, the estimated average time from seroconversion to first symptom is approximately 5 years and to AIDS approximately 8 years. Very few patients are diagnosed with AIDS the first 2 years after infection, but after that the risk seems to be 5-10% per year. Increasing use of anti-HIV medication will render studies of this kind difficult in the future. PMID- 2218404 TI - Streptococcal serogroup A epidemic in Norway 1987-1988. AB - A nationwide outbreak of Lancefield group A streptococcal (GAS) infections in Norway during the season 1987-88 is described. Data were collected from the Norwegian infectious disease notification system and supplemented by active search for cases of bacteraemia and other serious infections in addition to serotyping of selected clinical bacterial isolates. The number of reported cases of non-invasive GAS infections from week 29/1987 to week 28/1988 was 60% higher than expected. Between 1 Jan. and 30 June 1988, 84 cases of bacteraemia were notified, several with fulminant septicaemia and shock. The case fatality rate was 25%. Six cases of neonatal GAS septicaemia were seen. There was a nearly 3 fold total increase in occurrence of GAS bacteraemia compared with previous years, and the increase was marked particularly in cases among older children and adults 30-50 years old. Additional culture-confirmed diagnoses included unusual cases compared to recent decades such as pneumonia with empyema, necrotising fasciitis and primary peritonitis. Serotyping of strains collected consecutively from localized infections revealed a marked predominance of T-type 1, opacity factor negative strains (T-1 OF-), ranging from 41% in North Norway to 87% in Mid Norway. M-typing confirmed that these strains were M-1, as were 87% of the preserved bacteraemia strains from the period described. Although most of the M-1 strains were distinctly mucoid only one case of acute rheumatic fever was reported during the first half of 1988. We conclude that an epidemic of GAS infections caused by M-1 strains has occurred in Norway resulting in an increase in both incidence and seriousness of disease. PMID- 2218405 TI - Reappearance of group A streptococci in acute otitis media. AB - Specimens from acute otitis media (AOM) examined in the first quarter of the years 1986, 1987, 1988, and 1989 were reviewed in order to point out any changes in the bacteriological etiology. A total of 1,722 specimens were taken in the community and in the hospitals of a county of 500,000 inhabitants in the 4-year period: 447 (1986), 420 (1987), 388 (1988), 467 (1988). The majority of the specimens came from children less than 10 years of age. The specimen sampling technique differed between the various otologists, but their sampling techniques were constant through the years. Haemophilus influenzae was the most frequent isolate and held a constant incidence of 29.9% with little variation. In 1986-88 Streptococcus pneumoniae was the second (19.8%) and group A streptococci (GAS) the third (9.8%) most common agent in frequency. In 1989 a change in the etiologic agents was seen as GAS increased in frequency to 18.8% (p less than 0.001), while no significant changes occurred in the frequency of H. influenzae and S. pneumoniae. 33% of the specimens were negative in the whole period. It is too early to decide whether a transient epidemic has occurred or whether the findings announce a more constant change in etiology. PMID- 2218406 TI - Haemophilus isolated from unusual anatomical sites. AB - During a 15-year period Haemophilus species were isolated from unusual anatomical sites in 80 patients, mostly adults. The origin of specimens was pus and swabs from suppurative lesions, fluids from serosal cavities and gall bladder, gut content, and blood in cases with a supposed tissue focus. In 17 patients Haemophilus species were isolated in pure culture, in 63 patients in conjunction with other bacteria. 17 patients had gynaecological complaints: bartholinitis, salpingitis, and vaginal discharge. 22 patients had gastrointestinal complaints, comprising 17 with appendicitis, peritonitis following perforation of gastric ulcer, gall-duct infections, and an abscess in the stomach wall, and 5 patients with colonization of the gut. 41 patients had soft tissue and bone infections. PMID- 2218407 TI - Prevalence of IgM antibodies to nine Legionella species in Icelandic children. AB - In order to evaluate the prevalence of antibodies to Legionella species among children in Iceland, a prospective study was conducted in 424 children aged 1 month to 12 years, 28 of whom had an acute respiratory tract infection. Antibody titers to L. pneumophila serogroup 1-6, L. bozemanii, L. dumoffii, and L. micdadei were measured by microagglutination technique. Seroreactivity to Legionella spp. was found in 30% of the children greater than 3 years of age and in 22% of all children. The majority of the children with legionella antibodies had no history of previous or present respiratory tract infection. The children with previous pneumonia or bronchial asthma did not show a higher seroreactivity to legionella than children without such a history. Our observations suggests that Icelandic children are frequently exposed to Legionella species or closely related bacteria. PMID- 2218408 TI - Estimation of symptomatic and asymptomatic Salmonella infections. AB - Since the surveillance of salmonellosis in Sweden is primarily passive, it can be assumed that most of the asymptomatic salmonella infections are never identified. We here report the proportion of asymptomatic and symptomatic salmonella infections in Swedish travellers to different geographic areas as well as in "contacts" to index cases with salmonellosis. In the 346 travellers studied Salmonellae were isolated equally often among those who remained healthy (10/216; 4.6%) as in those with intestinal symptoms (7/130; 5.4%). Similarly, most of the salmonella-infected "contacts" to index cases (11/15; 73%) had an asymptomatic infection. No difference in the mean duration of excreting Salmonella in the stool was found between carriers with symptomatic and asymptomatic infection. The literature concerning transmission of nontyphi Salmonellae from carriers was reviewed. Since person to person transmission is rarely noted, screening for carriers may be limited to food handlers and hospital personnel taking care of patients susceptible to low infective doses of Salmonella. Similarly, follow-up faecal cultures in individuals with notified salmonella infection may be restricted to these groups. PMID- 2218409 TI - Toxigenic Escherichia coli associated with sudden infant death syndrome. AB - The role of Escherichia coli as a cause of sudden infant death syndrome was investigated prospectively. Strains of E. coli producing the heat labile enterotoxin (LT) or the Vero-cell cytotoxin (VT) were isolated from the intestinal contents of 21/46 infants who died from sudden infant death syndrome (SIDS). None were found in the contemporaneously sampled faeces of 24 normal live infants in the same area. Live infants were used as controls in the absence of dead infants who had not died of SIDS. This high incidence of toxigenic E. coli among the SIDS infants versus the low incidence in controls, together with the general rarity of finding such toxigenic E. coli in the community of a temperate developed country, made us conclude that there may be a causal relationship between toxigenic E. coli and SIDS. The O and H serotypes of the toxigenic E. coli associated with SIDS infants tended not to be those normally considered to be toxigenic. The toxigenicity appeared to be relatively labile. It is suggested that SIDS may be associated with the infant either acquiring these unusual types of E. coli or more likely that its normal resident E. coli acquire the plasmids to produce these toxins. PMID- 2218410 TI - Neonatal sepsis due to Streptococcus pneumoniae. AB - A 20-year-old primigravida in the 33rd week of gestation was delivered of a girl weighing 1,790 g 23 h after spontaneous rupture of the membranes. 13 h after birth, the child showed signs of shock. Cultures of blood, conjunctiva and nasopharyngeal aspirate grew Streptococcus pneumoniae of serotype 11. Cultures from the mother's cervix and from the placenta and membranes also grew S. pneumoniae of the same serotype. The infant responded well to ampicillin and netilmicin. The early-onset pneumococcal septicemic cases reported over the last 20 years are reviewed. PMID- 2218412 TI - Ciprofloxacin treatment of murine typhus. AB - A 31-year-old woman developed fever, severe headache, myalgia and rash 3 weeks after a visit to Cyprus where she experienced insect bites in her bed. Treatment with ciprofloxacin resulted in a remarkable and rapid effect. Endemic typhus was proved by serology. PMID- 2218411 TI - Fatal mucormycosis presenting as an appendiceal mass with metastatic spread to the liver during chemotherapy-induced granulocytopenia. AB - Opportunistic fungal infections occur with increasing frequency during chemotherapy induced granulocytopenia. A 27-year-old woman developed mucormycosis in the ileocecal region with fatal dissemination to the liver while receiving consolidation therapy for acute T-lymphoblastic leukemia. The infection occurred during a period of decreased colonization resistance in the intestinal tract. Early symptoms were high fever unresponsive to broad spectrum antibiotics, severe pain in the right lower abdominal quadrant and diarrhoea. This was followed by an infiltrate in the right abdomen, ileus, and icterus. Diagnosis was established in the living patient by thin needle aspiration from affected liver tissue. Giemsa's stain and fungal cultures revealed Mucor indicus. The fatal outcome of disseminated mucormycosis justifies a high index of suspicion and a maximal (invasive) diagnostic effort as localised infections might be cured by resection and amphotericin B. PMID- 2218413 TI - Successful aztreonam treatment of acute typhoid fever after chloramphenicol failure. AB - Aztreonam treatment was successful in 4 cases of typhoid fever. The patients were seriously ill with growth of Salmonella typhi in blood cultures despite treatment with chloramphenicol. Aztreonam appears to be a useful alternative to standard therapy of typhoid fever. PMID- 2218414 TI - Are tumor necrosis factor (TNF) or cortisol of value for the diagnosis of acute septicemia? AB - Early diagnosis is of great importance to improve the prognosis of septicemia. Traditional laboratory tests are either delayed like blood cultures, or unspecific like WBC count or ESR. In this retrospective pilot study we have assayed plasma cortisol, blood sugar and serum tumor necrosis factor (TNF) from patients with verified septicemia. With the approach used in this study none of the tests were able to differentiate between septicemia and other infectious febrile illnesses, or to predict if the causing organism was gram-positive or gram-negative. PMID- 2218415 TI - Invasive Haemophilus influenzae infections in adults: a patient with prosthetic valve endocarditis. PMID- 2218416 TI - The influence of quinolones on the faecal flora. AB - Ingestion of antimicrobial agents may in several ways influence the indigenous flora of the human digestive tract. The influence can be evaluated by following qualitative and/or quantitative alterations in the composition of the flora and of its antibiotic resistance profile (ARP). Another approach is to follow alterations in physiological and/or biochemical intestinal characteristics which depend on the intestinal flora. In a Norwegian-Swedish collaborative study, the influence of 10 orally given antimicrobial drugs on seven to nine various biochemical microflora-associated characteristics in groups of healthy volunteers was followed. In contrast to most of the other drugs given, ofloxacin exerted almost no influence upon the characteristics investigated. The result of this study are reviewed, as well as the results of other studies dealing with the influence of the quinolones on the faecal flora. PMID- 2218417 TI - The pharmacokinetics of oral quinolones (norfloxacin, ciprofloxacin, ofloxacin). AB - The newer fluoro-quinolones including norfloxacin, ciprofloxacin and ofloxacin are all characterized by a good penetration into tissues and cells. In contrast to beta-lactam antibiotics, these quinolones often achieve tissue concentrations which are several times higher than concurrent serum levels. Therefore, MIC values should not be related to serum concentrations only, when possibilities for the use of quinolones in tissue infections are discussed. Following oral administration, norfloxacin and ciprofloxacin are well absorbed and the bioavailability of ofloxacin is almost 100%. Absorption is delayed but not reduced by food. Ofloxacin is mainly excreted unchanged; norfloxacin and ciprofloxacin are metabolized to some extent, but most metabolites are biologically active. Half-lives of the drugs are 3-6 hours and they may therefore be administrated twice daily. These quinolones are excreted by glomerular filtration and tubular secretion but also via faeces. Dose reduction is needed only in patients with severe reduction of kidney function. It has been suggested that when renal function is reduced an increased transintestinal passage of the quinolones may result. In the intestines the quinolones seem to be bound to faeces; anaerobes are mainly unaffected by these antibiotics. PMID- 2218418 TI - Treatment of chlamydial infections. AB - Antibiotic therapy of chlamydial infections means treatment of an intracellular parasite. That is, the antibiotic drug has to pass not only over the cell membrane of the organism but also over the cell membrane of the host cell and over the membrane lining the intracytoplasmatic vacuole, where the chlamydiae reproduce. To what extent antibiotic may induce "latent" chlamydial infections is badly defined. Beta-lactam antibiotics in certain concentrations may induce cell wall-deficient forms of chlamydiae. Still there is non-conformity in performing in vitro susceptibility tests and diversed opinions of how to interpret such tests. For several antibiotics there is a discrepancy between the result of in vitro susceptibility tests and therapeutic trials. There is a need for long term follow-up studies of the effect of antibiotic therapy of genital chlamydial infections. Just less than half of such infections in females are complicated, i.e., cases of endometritis/salpingitis. It is very difficult to differentiate uncomplicated from complicated genital chlamydial infections without invasive tests. Approximately 40% of chlamydial cervicitis cases has a concomitant PID. Thus all genital chlamydial infections in females should be treated as complicated. PMID- 2218419 TI - Occurrence of Ureaplasma urealyticus and Mycoplasma hominis in non-gonococcal urethritis before and after treatment in a double-blind trial of ofloxacin versus erythromycin. AB - The efficacy of ofloxacin, a new quinolone derivate, was tested against that of erythromycin in a prospective double-blind trial in patients with non-gonococcal urethritis (NGU) with special reference to the occurrence of Mycoplasma hominis and Ureaplasma urealyticum. 188 male NGU patients were randomized to treatment with either ofloxacin 200 mg b.i.d. or erythromycin 500 mg b.i.d. for seven days. Before treatment eight (4.3%) patients, five in the erythromycin group and three in the ofloxacin group, were M. hominis positive. At follow-up day 8 and 15 after start of treatment all five in the erythromycin group and two in the ofloxacin group were still positive. U. urealyticum was recovered in 16 patients (8.5%) before treatment. One patient was still positive in the erythromycin group when examined day 15, whereas all patients were negative in the ofloxacin group at both follow-up controls. Clinically, the efficacy of treatment day 15 was 77.4% in the erythromycin group and 84.3% in the ofloxacin group. The difference was not significant. Side-effects occurred in 38.5% in the erythromycin group and in 21.3% in the ofloxacin group. This difference is significant. Ofloxacin is effective in the treatment of NGU in males and is an alternative to conventional antibiotic treatment. PMID- 2218420 TI - Ofloxacin in urinary tract infections. AB - Ofloxacin belongs to a new generation of fluorinated quinolones which are structurally related to nalidixic acid. It is an orally or parenterally administered antibacterial drug active against most Gram-negative aerobic bacteria, many Gram-positive bacteria and some anaerobes. The pharmacokinetic profile or ofloxacin shows a rapid gastrointestinal absorption and high concentrations are achieved in most tissues and body fluids. Clinical efficacy of ofloxacin has been demonstrated in a variety of systemic infections as well as in acute and chronic urinary tract infections and ofloxacin has generally appeared to be at least as effective as comparative orally administered antibiotics. Ofloxacin is well tolerated and bacterial resistance does not appear to develop readily, however, noncritical use of quinolones in simple infections where standard drugs may be equally effective and safe should be discouraged. In conclusion, ofloxacin is an orally active drug which offers a valuable alternative to other broad spectrum antibacterial drugs. PMID- 2218421 TI - Oral ofloxacin once daily and doxycycline in the treatment of acute exacerbations of chronic bronchitis. AB - 192 patients, most of them ambulatory, with acute exacerbation of chronic bronchitis were treated with 10- to 14-day courses of oral ofloxacin receiving 400 mg once daily or doxycycline first 200 mg and then 100 mg once daily in this randomized observer-blinded multicentre study. 98 patients were included in the ofloxacin group and 94 in the doxycycline group. The clinical efficacy was 86/87 (98.8%) in the ofloxacin group and 87/91 (91.2%) in the doxycycline group. The bacteriological efficacy was 31/34 (91.2%) in the ofloxacin group and 19/24 (79.2%) in the doxycycline group. Some patients had more than one pathogen. There was no statistically significant difference in efficacy between the two treatment groups; both treatments were highly effective and well tolerated. The adverse events showed an expected pattern. Ofloxacin treatment was discontinued in three patients. In conclusion, both treatments were found to have similar safety and efficacy and were well tolerated when used for treatment of acute exacerbations of chronic bronchitis. PMID- 2218422 TI - A comparative study of ofloxacin and pivmecillinam in acute exacerbations of chronic bronchitis. AB - In a double-blind study in 84 patients with chronic bronchitis and purulent exacerbations, ofloxacin 200 mg b.i.d. and pivampicillin 700 mg t.i.d., were compared with respect to efficacy and safety. Both treatments resulted in a uniform and very high bacteriological elimination rate (94.1% to 97.2%) and clinical cure rate (97.4% to 97.6%). There were, however, signs of fewer adverse reactions and a better patient acceptance in the ofloxacin group. PMID- 2218423 TI - Prospective randomized clinical trials of new quinolones versus beta-lactam antibiotics in lower respiratory tract infections. AB - In four prospective randomized clinical trials between November 1983 and March 1988, we studied 270 patients with severe bacterial infections, mainly lower respiratory tract ones. We compared ciprofloxacin and imipenem/cilastatin in the first study, ciprofloxacin and ofloxacin in the second study, ciprofloxacin and ticarcillin/clavulanic acid in the third study, and ofloxacin and cefpirome in the fourth study. A total of 90 pneumonias, 139 LRTIs, 22 septicaemias and 19 other bacterial infections were treated; the dominant pathogens were Pseudomonas aeruginosa and enterobacteria. Clinical success rates were high; cure or improvement was registered in 89% of the patients on ciprofloxacin, 89% on ofloxacin and 85% on beta-lactams. Treatment failures occurred mainly in ICU patients with terminal underlying diseases. Bacteriologically, eradication rates were high for enterobacteria and Staphylococcus aureus, but a relatively high persistence rate was seen for P. aeruginosa due to increased resistance and/or specific type and location of the infections. The incidence of side-effects was relatively high (23%-29%) which was related to careful monitoring. Adverse effects were group-specific (CNS reactions with quinolones, diarrhoea with beta lactam antibiotics). PMID- 2218424 TI - Overview of experience with ofloxacin in respiratory tract infection. AB - Ofloxacin is highly active against common respiratory pathogens including Haemophilus influenzae and Branhamella catarrhalis and has clinically applicable activity against Streptococcus pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa. Sputum, lung tissue and bronchial mucosal concentrations of ofloxacin equal or, in most cases significantly exceed the MICs of such pathogens. These in vitro attributes are reflected in the results of the worldwide ofloxacin clinical trial program which achieved overall response rates of 98% in lower respiratory tract infections, 83% in pneumonias and 87% to 95%, in open and comparative studies respectively, in patients with acute exacerbations of chronic bronchitis (CB). Overall bacterial eradication rates ranged from 70% for pneumococci and 84.5% for B. catarrhalis to 88.5% for H. influenzae. In lower respiratory infection ofloxacin gave equal or superior clinical results to amoxycillin or erythromycin therapy together with an overall bacterial eradication rate of 100%. Clinical results comparable with standard agents were also obtained in pneumonia, cure rates ranging from 77-89% at various dosages. Eradication rates proved greatest for H. influenzae (92%) and were satisfactory for Klebsiella spp. (80%), although less so for pneumococci (73%). Bacteriological eradication rates in acute exacerbations of chronic bronchitis ranged from 68% for pneumococcal infections, to 85% in B. catarrhalis and 94% in H. influenzae infections. Ofloxacin compared favourably with pivampicillin, co-trimoxazole and doxycycline clinically. A daily oral ofloxacin dose of 400 mg produced a good clinical response in 92% of patients or more. The available clinical data therefore substantially confirm the claim of ofloxacin to offer an effective alternative in many forms of acute bacterial respiratory infection, especially where H. influenzae and B. catarrhalis are involved. PMID- 2218425 TI - Clinical experience with parenteral and oral ofloxacin in severe infections. AB - This study included 107 patients who were given ofloxacin at daily doses of 400 800 mg for 10 days to 12 months for treatment of a variety of infections. 77 patients were given ofloxacin orally and 30 received it intravenously. Infections treated were bronchopneumonia (29), chronic bronchitis with acute exacerbation (15), chronic osteomyelitis with exacerbation (20), soft tissue infections (13), complicated urinary tract infections (7), chronic prostatis with exacerbation (7), malignant external otitis (4), or other infections (12). Pathogens included Pseudomonas aeruginosa (39), Acinetobacter spp. (9), various Enterobacteriaceae (30), Haemophilus influenzae (26), pneumococci (1) and Staphylococcus aureus (4). MICs of ofloxacin ranged from less than 0.06-2 mg/l. Clinically, 69% of the patients were cured, 18% improved and 13% failed to respond. Bacteriologically, pathogens were eradicated in 70%, persisted in 16% and relapsed in 14%. Resistance during therapy developed almost exclusively in P. aeruginosa strains (17.9%). The following adverse reactions were reported: gastrointestinal disturbances (6), rash plus facial oedema (1), abnormal liver function tests (5) and leukopenia (1). It is concluded that ofloxacin is suitable for treatment of a variety of infections, ranging from serious life threatening infections in ICU patients to chronic ones that require prolonged therapy. PMID- 2218426 TI - Resistance situation of oral antibiotics in the Scandinavian countries with special reference to the fluoro-quinolones. AB - In general, the Scandinavian countries have a rather conservative attitude towards new antimicrobial agents. Our antibiotic policies are based upon many years of clinical and laboratory experiences. It is generally believed, although not always satisfactorily proven, that our relatively restrictive attitude to the use of new as well as of older antimicrobial drugs by one mechanism or another, is a matter of some importance when explaining the relatively low antibiotic resistance profile (ARP) existing in most places in Scandinavia. When a new group of drugs, such as the quinolones, is going to be introduced in the therapeutic armamentarium, the existing ARPs of the microbes actually involved have to be taken into consideration. PMID- 2218427 TI - Swedish Association of Urology. Proceedings of the annual spring meeting 1990. Lund, May 3-4, 1990. Abstracts. PMID- 2218428 TI - Frozen shoulder: current concepts. AB - The literature on frozen shoulder (FS) is reviewed. The etiology of FS is still not known and our understanding of the pathogenesis is limited. Studies on treatment programs under controlled conditions are few and incomplete. Further research is urgently needed. PMID- 2218429 TI - Distribution of Gm allotypes in juvenile chronic arthritis. AB - The immunoglobulin allotypes G1m(a), G1m(x), G2m(n), G3m(b) and Km(1) were determined in 76 Swedish patients with juvenile chronic arthritis (JCA). Eight of the patients had the systemic form of the disease. 37 belonged to the polyarticular and 31 to the oligoarticular subset. The frequency of the G1ma(x), G3m-b haplotype was significantly increased in the polyarticular subset but not in the oligoarticular subset, compared with the normal population (p less than 0.01). The polyarticular subset also differed from the oligoarticular subset with increased frequency (p less than 0.01) and higher levels (p less than 0.01) of IgM rheumatoid factor and a lower rate of remission (p less than 0.05). The few JCA patients in the systemic subset showed similar features as the polyarticular patients. The frequencies of G2m(n) and Km(1) did not deviate from the expected in any of the JCA subsets. PMID- 2218430 TI - IgG and IgA subclass distribution of total immunoglobulin and rheumatoid factors in rheumatoid tissue plasma cells. AB - The subclass distribution of IgG and IgA plasma cells, and in IgG and IgA rheumatoid factor (RF) producing cells was studied in sections of synovial tissue from seropositive RA and various types of seronegative arthritis, including ankylosing spondylitis, psoriatic arthritis, and Reiter's syndrome. The study was performed with immunofluorescence technique and monoclonal IgG and IgA subclass specific antibodies. IgG RF producing cells were identified by their ability to bind and activate factors both in the early (C3) and late (C5b-9) part of the complement cascade. IgA RF cells were identified by double staining experiments with heat-aggregated IgG and monoclonal antibodies to IgA subclasses. In 23 tissues tested for total IgG, IgG1 cells were usually predominant, while the frequency of IgG3 cells was usually higher than that of IgG2. In 19 tissues also tested for IgA, both IgA subclasses were present in all tissues. IgA1 plasma cells were always predominant, with a mean ratio of IgA1 to IgA2 cells of approximately 10. In the 13 tissues tested for RF-producing cells, the highest frequency of IgG RF cells was found among the IgG3 cells, followed by IgG1 and IgG2. IgA RF cells were found in only one case, all cells being IgA1. PMID- 2218431 TI - Salmonella-reactive synovial fluid T-cell clones in a patient with post infectious Salmonella arthritis. AB - From a patient with reactive arthritis following Salmonella typhimurium enteritis, synovial fluid T-lymphocytes were cloned and expanded in vitro. Seven out of 74 clones showed a marked proliferative response to antigens of heat killed Salmonella typhimurium with autologous T-cell-depleted peripheral blood mononuclear cells as antigen-presenting cells. The Salmonella-reactive clones were of the CD4+ phenotype, antigen-induced proliferation could be inhibited by a monoclonal antibody to HLA class II. One clone recognized both Salmonella and Campylobacter jejuni antigens in the proliferation assay. The multiclonality of Salmonella-reactive synovial fluid T-cells indicates that the microorganisms have been present, at least transiently, within the affected joint and thus recruited specific T-lymphocytes that might initiate synovitis. PMID- 2218433 TI - Functional and psychosocial consequences of disease and experience of pain and exertion in a group of rheumatic patients considered for active training. Result of a survey in Bollnas Medical District. I. AB - The purpose of this study was to select and describe a group of RA patients within a defined area who had, on clinical grounds, been considered for active training. The material consisted of 69 patients with classical or definite RA. It comprised half of the RA patients known to the clinic. The patients were assessed by means of a questionnaire, functional tests with rating of activity-induced pain, a cycling-test with rating of perceived exertion, and an interview by a psychologist. Subjective disease consequences were pain and stiffness. 38% of the patients never or seldom exercised. 72% wished to increase their activity but were prevented by pain. The functional tests indicated slow performance and considerable pain in activities of daily life. The interview disclosed above all, a low degree of self-confidence. Generalized pain and functional impairment correlated slightly with psychosocial factors. The results of the study indicate the need for active training as one strategy to alleviate pain and to maintain functional capacity in RA patients. PMID- 2218432 TI - Signs and symptoms in the masticatory system in ten patients with mixed connective tissue disease. AB - Ten patients with mixed connective tissue disease (MCTD) were examined for signs and symptoms in the masticatory system. The study included clinical, radiological, histological and immunohistochemical examinations. The status of the teeth and periodontium did not seem to differ from that found in the general Finnish population. All 10 patients showed clinical dysfunction, and 7 had additional radiographic changes of the temporomandibular joints. Sialopenia was observed in 7 patients, and histological examination revealed sialoadenitis with a focus score exceeding 1 in the labial salivary glands in 9 patients. Only 1 patient had clinically detectable mucosal lesions. However, in 5 of 6 patients with normal-appearing mucosa, histological examination revealed chronic inflammation. Three of the 10 patients had clinically atrophic and erythematous oral mucosa; histological examination again revealed chronic inflammation. The signs and symptoms appearing in the masticatory system of these 10 MCTD patients were many and varied and indicate the importance of closely examining all oral structures. As with other connective tissue diseases, MCTD should be treated on a multidisciplinary basis. PMID- 2218434 TI - Methimazole and arthritis. PMID- 2218435 TI - Type A behaviour in pre-school children: interrater reliability, stability over six months and subcomponents. AB - Type A behaviour was measured in 250 boys and 245 girls (ages 3-7) using a Swedish version of Matthews' Youth Test for Health (MYTH). In addition, speech and voice characteristics (speed, loudness, response latency) were measured. Each child was independently rated by two play group leaders and measurements were repeated after a six month interval. Interrater reliability (first session) was 0.76 for both sexes and did not change with the age of the child. Boys obtained significantly (p less than 0.0001) higher scores than girls. Correlations over the six month period were 0.64 and 0.60 (p less than 0.001) for the two possible combinations of different raters and slightly higher (0.75 and 0.68, p less than 0.001) when the same rater was used. Two components of Type A behaviour were identified from a factor analysis of the data: impatience and competitiveness, and they accounted for 57% of the total variance. As for the total scale, boys obtained significantly higher scores than girls on both subscales. Scores on the competitiveness scale increased systematically with age. Speech and voice characteristics correlated significantly with Type A scores (total Type A behaviour: r = 0.50, using different raters, and 0.71, using the same raters, p less than 0.001) and, once again, boys obtained significantly (p less than 0.001) higher scores than girls. The results are in close agreement with the American findings from the original scale. It was concluded that the scale provides a reliable and valid instrument for measuring Type A or Type A-like behaviours in pre-school children. PMID- 2218436 TI - Mice selectively bred for an open field activity increase after maze learning. AB - A unidirectional selective breeding experiment performed over six generations resulted in a line of mice (S6), which differed from the maintained unselected Swiss albino strain, called normal (N) strain, in the following respects: S6 mice increased their open field activity after maze learning significantly more than N mice. S6 mice ambulated more and exhibited more thigmotactic behaviour in a circular open field than N mice. S6 mice were superior than N mice in regard to maze learning capacity. Finally, S6 mice were interpreted as significantly less emotional according to their defecation, more responsive to novelty according to their urine pattern and more aggressive than N mice. PMID- 2218437 TI - Rod suppression of cone-mediated information about colour and form during dark adaptation. AB - Following substantial bleaches, the specific form and hue thresholds were measured during dark adaptation with a test stimulus of 1 x 2 degrees at 40 degrees extrafoveally. The wavelength of the test field was varied between runs. The results show that both thresholds started to rise at about the cone-rod break of the dark-adaptation curve, irrespective of wavelength used in the test. Furthermore, the specific threshold for form was found to rise when a scotopic stimulus was superimposed on a photopic test flash. On the other hand, both thresholds remained at the cone-plateau level when the test flash was confined within the rod-free fovea. In order to explain the rise in the specific thresholds, it is suggested that signals from rods generated directly in response to the test stimulus may suppress both cone-mediated form and colour. It is also suggested that this type of rod-cone interaction represents a general characteristic involved in several kinds of visual information processing. PMID- 2218438 TI - Psychometric properties of the Danish MCMI-I translation. AB - A translation of the MCMI-I has been in use in Denmark for some years. An untested assumption in the interpretation of the pattern of test results is that the psychometric characteristics of the Danish and American versions are similar. The purpose of this study was to evaluate the psychometric properties of the questionnaire by using traditional psychometric analysis techniques on the results of a sample consisting of 423 patients and 179 normal controls. Coefficient alpha was calculated for the 20 clinical subscales of the test and the Danish results were strikingly similar to the original coefficients reported by Millon. Furthermore, factor analysis of the subscales showed a factor structure very similar to American findings, and it is concluded that the psychometric properties of the Danish MCMI are not significantly different from the original. PMID- 2218439 TI - On the distinction between perception and cognition. AB - To uphold the distinction between perception and cognition for certain classes of tasks or phenomena, it is proposed that three criteria must be met: (1) when perceptual and cognitive functions serve different biological purposes, (2) when stimulus information in dynamic events is necessary, but not sufficient for veridical perception, and (3) when the task emphasizes explicit retrieval, as opposed to implicit use of information. Conversely, when the three criteria have not been met, conditions for theoretical unification exist. PMID- 2218440 TI - Personality organization defined by DMT and the Structural Interview. AB - The psychoanalytic concept of Personality Organization (PO) may be operationalized by means of a Structural Interview as well as by means of psychological tests. The present study utilized the Structural Interview and a projective test called the Defence Mechanism Test (DMT) to operationalize the PO concept on a sample of 50 psychiatric inpatients. The reliability of the PO judgements were found to be acceptable for both the Structural Interview and the DMT. The validity, which was estimated as the correlation between the two methods, was also found to be substantial. The conclusion is that the concept of PO may be reliably operationalized for psychiatric patients and seems to have concurrent validity. Both the DMT and the Structural Interview may be used for differential diagnosis of PO. PMID- 2218441 TI - Tachistoscopic and questionnaire methods for the measurement of psychological defences. AB - Only few attempts have been made to compare different methods aiming at quantifying defensive strategies. In this study the tachistoscopic Defence Mechanism Test (Kragh, 1960b and 1985) is compared to paper-and-pencil tests of defence. There were virtually no correlations between the DMT and the other measures of defence. This may indicate that the concept of defence is a highly complex one. It is suggested that the Defence Mechanism Test may be measuring primary defence while defence questionnaires may be assessing more secondary forms of defence. The two questionnaires used for assessing defence correlated significantly, while a scale for social desirability showed no correlation with DMT or the two defence questionnaires. PMID- 2218442 TI - Rorschach-profile in panic disorder. AB - The Rorschach test was applied to four groups: 41 Panic Disorder (PD), 14 Major Depression (MD), 11 Generalized Anxiety Disorder (GAD) and 18 normal subjects. The aims were to describe the test profile of PD patients and to discuss implications for cognitive processing ability and personality structure. A hypothesis of a borderline personality structure in PD patients, based on psychodynamic literature, was tested, but was not unambiguously supported. A "loose", borderline-like personality structure and disturbances in processing abilities, however, characterized PD-patients. The normal subjects surprisingly provided many Fabulized Combinations, a response type, considered suspect of borderline pathology, but also showed more signs of integrative and synthesizing abilities than the other groups. PMID- 2218443 TI - [Airport malaria: mini-epidemic in Switzerland]. AB - Five cases of airport malaria were observed in Geneva in the summer of 1989. All the patients lived within 2 km of Geneva-Cointrin International Airport. They were hospitalized between July 14 and August 2 for high fever. None had received a recent blood transfusion, an i.v. injection or traveled to a tropical country, except for one, a former pilot, whose last brief visit had been a year earlier. High minimum temperatures between July 6 and 10 in all likelihood allowed the survival of infected anopheles introduced by an aircraft. P. falciparum was identified in the blood smears of all the patients. Four had one or more symptoms of serious malaria and received intravenous treatment. In the fifth patient, treatment with cotrimoxazole for suspected acute pyelonephritis made diagnosis particularly difficult because the malaria infection was partially controlled by the antibiotic therapy. The time necessary for diagnosis of malaria varied from 5 to 31 days in the 5 cases. Airport malaria has been observed over the past twenty years in Europe, particularly in the summer, and is often serious because of late diagnosis and the type of plasmodium most frequently involved, P. falciparum. This diagnosis should be considered in patients with high fever of unknown origin, even when they have not travelled to an endemic zone. PMID- 2218444 TI - [Isolated trochlear nerve paralysis following head trauma]. AB - 39 cases with isolated trochlear nerve palsies of traumatic origin have been analyzed retrospectively. 18 patients (46%) had had cerebral contusion, 15 (39%) cerebral concussion, and 6 patients (15%) a minor head trauma. 33 patients had unilateral trochlear nerve palsies and 6 (all of them with cerebral contusion) bilateral. The degree of the palsies did not correlate with the severity of the head trauma. Essential pathogenetic mechanisms were frontal or occipital blows. We emphasize a fact hitherto underestimated in the literature, that even a relatively mild head trauma (cerebral concussion or minor head trauma) can cause isolated trochlear nerve palsies. This was the case in 21 of our 39 patients (54%). Simple clinical examination techniques are described (Bielschowsky phenomenon, pencil test), which allow detection of trochlear nerve palsies in most cases. PMID- 2218445 TI - [Chronic urticaria and acquired complement deficiency due to a nephritic factor (C3NeF)]. AB - Several studies have suggested that complement activation processes are frequently involved in the pathogenesis of urticaria. We report clinical evolution and studies of complement-mediated functions in a 47-year-old previously described patient presenting with chronic urticaria, in whom we found persistent low complement hemolytic activity (65-75% of normal values), depressed levels of third complement component (C3, between 55% and 65%) and of factor B (between 60% and 75%), together with C1, C4, C2, C5, C5b neoantigen and fluid phase terminal complement (SC5b-9) complex within the normal range, pointing to activation of the alternative pathway. A circulating low affinity C3 nephritic factor (C3NeF), known to enhance cleavage of human serum C3, was detected. The urticarial lesions, which were initially pruritic and persisted for less than 24 hours, became subsequently fixed and burning, and were accompanied by fever and arthralgia. Skin biopsy specimens showed moderate leukocytoclastic vasculitis. Response to varied treatment regimens, including antihistamines and colchicine, was poor. Therapy with oral corticosteroids produced some improvement. The association of chronic urticaria with C3NeF without clinical and biological signs of membranoproliferative glomerulonephritis and partial lipodystrophy has not to our knowledge been reported before. This observation raises the question of a possible role of C3NeF in the pathogenesis of urticaria. PMID- 2218446 TI - [X-chromosomal adrenoleukodystrophy. A peroxisomal disease important for differential diagnosis in the internal medicine-neurological field]. AB - Clinically, X-chromosomal adrenoleukodystrophy is characterized by a variable neurological symptomatology and non-obligatory adrenocortical insufficiency. The underlying pathogenetic mechanism consists of a disturbance of the peroxisomal metabolism of fatty acids with consecutive accumulation of very long chain fatty acids (VLCFA) in the blood. The diagnosis of this rare condition is important in view of the possibility of special dietary treatment and genetic counseling of the family. PMID- 2218447 TI - [Etiology of diarrheal diseases in immunocompetent and HIV-positive patients]. AB - In 1986 and 1987 the stool samples of 206 patients of the Medical Outpatient Clinic Basel were examined prospectively for bacteria, protozoa and worms. Clinical data of the patients were recorded by questionnaire. The patient group comprised 63 immunocompetent patients as well as 23 HIV-infected patients, all with symptoms of acute enteritis. The control group consisted of 120 healthy persons. Pathogenic organisms were found in the stools of 17.5% of the immunocompetent patients with enteritis. The most common germs were Campylobacter jejuni, Giardia lamblia and Salmonella enteritidis. Isospora belli, found in 2 cases (8.7%), was the only pathogen found in HIV-infected patients. The most frequent pathogen found in 7.5% of the control group was Giardia lamblia. The facultative pathogenic protozoon Blastocystis hominis was found in 16.7-19.0% of the 3 groups. There was no correlation between clinical symptoms and the results of stool examinations. Stool examinations in the immunocompetent patients corresponded to the known distribution of pathogenic germs in Switzerland. The homogeneous distribution of Blastocystis hominis in the 3 groups examined proves the high rate of infection. There is no evidence of a significant correlation between clinical symptoms of enteritis and infection with Blastocystis hominis in immunocompetent patients. PMID- 2218448 TI - [Magnetic resonance in oncology]. AB - The physical and biological background to magnetic resonance imaging (MRI) in patients with neoplasms is reviewed. The clinical indications for this method of diagnosis, staging, and follow-up of malignant neoplasms are discussed on the basis of the guidelines given by the MRI Consensus Conference on April 25-26, 1989, in Berne. MRI is the modality of choice in patients with neoplasms of the central nervous system and the musculoskeletal system. Further emerging indications for MRI are neoplasma of the ENT region, liver, and pelvic organs. Finally, the foreseeable developments in MRI and in magnetic resonance spectroscopy (MRS) are mentioned. PMID- 2218449 TI - [Approach in metastasis with unknown primary tumor]. AB - Metastases of an occult primary malignancy are quite common (5-10%), especially in lymph nodes, lung and bone. The search for the unknown primary is an intellectual challenge. Thorough history, meticulous physical examination, and economically and carefully directed additional investigations are the best methods of detecting a treatable malignancy. Even extensive standardized work-up, using all available laboratory and imaging techniques, may miss the primary tumor quite often and unnecessarily burden patients with poor prognosis. Prognostically and therapeutically distinct subgroups must be treated differently. PMID- 2218450 TI - [Vestibular disorders in Parkinson patients]. AB - Patients suffering from Parkinson's disease frequently complain of dizziness, postural instability and falls. Vestibular tests have been performed in 30 parkinsonian patients and in 28 controls. The results suggest a central vestibular disturbance in Parkinson's disease which correlates with the clinical disability. This vestibular disturbance is assumed to be due to dysfunction of the nigro-striato-collicular tracts. PMID- 2218451 TI - [Treatment of achalasia using balloon dilatation]. AB - 40 patients with achalasia underwent pneumatic dilatation. 25 were followed up for a mean duration of 3.96 years. Digestive symptoms disappeared in 32% of cases, were diminished in 40% and remained unchanged in 28%. In 8 patients oesophageal manometry after dilatation showed a significant reduction in lower oesophageal sphincter pressure. The patients showing improvement had a more marked drop in lower oesophageal sphincter pressure, lower residual pressure in the lower oesophageal sphincter measured by wet swallows, and negative pressure in the oesophagus. As complications 3 patients developed oesophageal perforation with one subsequent death, and 3 symptomatic gastro-oesophageal reflux. In view of these results, we regard pneumatic dilatation as the treatment of choice in achalasia. PMID- 2218453 TI - [Reversible microangiopathies following massive weight loss]. AB - A 17-year-old patient presented with loss of weight, acrocyanosis and trophic lesions of the tips of the toes. There were no clinical or immunological signs of connective tissue disease. Capillary microscopy revealed a severe organic microangiopathy and arteriolar spasm. A change in the patient's occupational conflict situation was followed by complete recovery and capillary findings normalized. The possible connection between anorexia-like affection and capillariopathy remains unclear. PMID- 2218452 TI - [Cardiac sources of cerebral embolism and infarction: results of the Lausanne register for cerebrovascular accidents]. AB - We studied 305 patients with a first stroke and a potential cardiac source of embolism (PCSE), on the basis of the Lausanne Stroke Registry. We have compared these patients with 1006 patients with stroke but without PCSE, admitted into the Registry during the same period, in order to assess the potential role of PCSE and the coexistence of other causes of stroke. Analysis of the various types of PCSE suggests that some neurologic characteristics are more frequent in patients with than without PCSE (infarcts of the posterior division of middle cerebral artery with Wernicke's aphasia and lateral hemianopia; maximal neurologic deficit at onset; haemorrhagic infarcts). PMID- 2218454 TI - [Bilateral radial nerve paralysis. Diagnostic and differential diagnostic aspects]. AB - Bilateral radial nerve palsies are rare, and hence in this situation an underlying generalized peripheral neuropathy must always be considered. Among 103 patients with radial nerve palsies seen at our department during the last five years, there were three cases presenting with bilateral non-traumatic radial nerve palsies. These patients are presented in detail. One had a bilateral nerve entrapment in the supinator channel associated with a neuropathy of unclear origin, the second had bilateral sleep palsy, and the third had mononeuropathy multiplex associated with HIV infection. Following a summary of the cases reported in the literature, diagnostic considerations and additional investigations are discussed. PMID- 2218455 TI - [Analysis of the frequency of anti-HLA hyperimmunization in patients with kidney transplantation]. AB - Highly sensitized patients tend to accumulate on renal transplant waiting lists. A long period of time is often needed for the identification of a compatible graft possessing the rare HLA antigens against which these patients are not immunized. The aim of this study was to identify factors which could explain the fact that the percentage of highly sensitized patients on the Swiss waiting list is one of the highest in Europe. Although no definite conclusion is possible, it seems that this phenomenon is not related to the fact that many of these patients have received mismatched grafts. It seems rather to result from the relatively high rate of transplantations for non-sensitized versus highly sensitized patients in comparison to what is encountered in other countries. The fact that this probably represents only a relative increase in hypersensitized patients is confirmed by the stability of the absolute number of these patients on the waiting list during recent years. PMID- 2218456 TI - [Isocyanate-induced respiratory tract diseases in Switzerland]. AB - From 1980 to 1986 the Swiss National Accident Insurance Company (SUVA) recognized isocyanate-induced airway diseases as an occupational illness in 245 cases, which are presented retrospectively. Since isocyanates are widely used they are found at a large variety of workplaces. At present, isocyanates are the most frequent cause of occupational asthma in the Swiss industrial field. After complete avoidance of any further exposure respiratory symptoms persisted or airway obstruction could still be documented in one third of patients. An unfavourable prognosis is significantly associated with the following factors: (1) bronchial obstruction (FEVl/VC) at first pulmonary function test; (2) RAST positive for isocyanates; (3) long latency period between onset of symptoms and end of exposure. Therefore, individuals with isocyanate-induced airway diseases must be immediately removed from any further exposure to these substances. PMID- 2218457 TI - [East African sleeping sickness (Trypanosoma rhodesiense infection) in 2 Swiss travelers to the tropics]. AB - We report on two Swiss travellers who acquired African sleeping sickness (Trypanosoma rhodesiense) the same day while visiting the Akagera park in Rwanda. The first patient developed clinical signs of sleeping sickness 8 days after being bitten by a tsetse fly. Trypanosomes were demonstrated in the blood and CSF. The other patient fell ill 13 days after the bite and trypanosomes were found only in blood samples. The first patient (cerebral trypanosomiasis), was treated with melarsoprol. He developed an allergic reaction under treatment but made a good recovery 4 months later. The second patient (hemo-lymphatic trypanosomiasis) was put on suramin, which was well tolerated. He recovered after 2 months. PMID- 2218458 TI - [Preventive and therapeutic measures in cytostatic-associated toxicity]. AB - Strategies (both prophylactic and therapeutic) to reduce side effects of chemotherapy are reviewed. In particular, issues concerning proper patient information are discussed which should help to increase patient compliance. Chemotherapy, especially regimens with a curative intent, must normally be administered under the guidance of an oncologist. However, close cooperation with the general practitioner is essential in order to ensure high quality counselling and treatment of the outpatient. PMID- 2218459 TI - [Chronic gastritis. Pathogenesis, clinical aspects and therapy]. AB - Based on clinical and histopathological features, three different types of chronic gastritis can be distinguished: gastritis A is confined to the proximal stomach and is the result of an autoimmunological process with antibodies against parietal cells and intrinsic factor. It is a rare disorder and may lead to pernicious anaemia. Distal, antral gastritis B is caused by an infection of the gastric mucosa with Helicobacter pylori (HP). Its incidence increases with age (greater than 50% above age 50). Gastritis C may be caused by drugs and alcohol but is mainly found in gastric remnants after partial resection as a consequence of biliary reflux. Gastritis A rarely causes symptoms. A relationship between gastritis B and C and non-ulcer dyspepsia (NUD) is highly controversial. Gastritis B is very closely associated with peptic ulcer disease. HP-positive antral gastritis seems to be the prerequisite for ulcer formation. All 3 types of gastritis carry an increased risk of malignancy, which seems to be positively correlated with hypoacidity, the chronicity of the inflammation and the histopathological feature of intestinal metaplasia. Noninvasive diagnostic tests (serology, breath tests, scintigraphy) are available, but the diagnosis of gastritis is still mainly based on endoscopy and biopsy. Treatment of gastritis A is not possible. Gastritis B can be healed by eradication of HP using bismuth salts and antibiotics but only combinations of 2-3 compounds seem to afford long term positive results. Further clinical trials are needed to determine whether such treatment is justified in patients with gastritis and NUD. In patients with chronic recurrent peptic ulcers eradication of HP prevents relapses and heals ulcer disease. Gastritis C complicated by severe symptoms or ulcer can only be successfully treated by a biliary diversion, i.e. Roux-Y-gastrojejunostomy. The discovery that gastritis B is caused by HP improves our understanding of peptic ulcer disease and will change therapeutic concepts. PMID- 2218460 TI - [The histological diagnosis of chronic gastritis. A German proposal for an integrated nomenclature]. AB - The Gastrointestinal Pathology Study Group of the German Pathological Society has drawn up a proposal for a unifying nomenclature for the graduation and classification of gastritis. The severity of chronic gastritis is divided into 4 grades (minimal, light, moderate and severe) and the activity of the process is characterized by 3 grades (grade 1, 2 and 3 activity). In addition, the presence or absence of Helicobacter pylori (formerly Campylobacter pylori), the extent and type of intestinal metaplasia, and the degree of glandular atrophy are recorded. To the two already well established types of gastritis (type A and type B) a third type is added, type C gastritis due to biliary reflux or other chemical, mechanical or toxic influences. PMID- 2218461 TI - [HIV epidemic: a study among physicians in Vaud]. AB - A two-phase survey was conducted in the Canton of Vaud among the 1006 registered private practitioners (response rate 98%). The first phase aimed at determining the proportion of these physicians involved in the care of HIV+ persons. The results showed that 43% of the practitioners had been consulted by HIV+ patients. In the second phase, all institutions (hospitals, prisons and IV-drug user rehabilitation and testing centers) and a representative sample of the physicians with HIV+ patients were asked about the transmission category of their HIV+ patients. A mathematical method was used to estimate the true number of known HIV+ individuals by December 1988. Approximately 60% of the HIV+ persons had been seen exclusively by the private practitioners. IV-drug users represented 57% of all HIV+ persons compared to only 27% of the AIDS cases registered in 1988, suggesting that an important change in the transmission categories of AIDS cases is to be expected in the near future. These observations underscore the evolving nature of the HIV epidemic on the one hand, and the crucial role of the private practitioners in the prevention of the HIV infection on the other. This also points to the need for methods specifically designed to monitor HIV and AIDS epidemics respectively. PMID- 2218462 TI - [Posterior shoulder dislocation. An often overlooked injury]. AB - Posterior dislocation of the shoulder is rare. Only 2% of dislocated shoulders are displaced posteriorly, and these are chiefly of the subacromial type. Over 60% of the cases are not diagnosed initially because the arm is held in the normal position of adduction and internal rotation. The most consistent findings on physical examination are: the fixed internal rotation of the arm and the characteristic movement of the scapula with abduction of the upper extremity. It is essential that appropriate radiographs are obtained to correctly diagnose the dislocation. While the routine anteroposterior shoulder film is often enough to diagnose various anterior dislocations, it is not sufficient to diagnose the subacromial type of posterior dislocation. We recommend an anteroposterior view and an axillary lateral or tangential scapula view. PMID- 2218463 TI - [Atherosclerotic nephropathy. Clinical manifestations of chronic arterial circulatory insufficiency of the kidneys]. AB - Atherosclerotic nephropathy is defined as renal insufficiency due to atheromatous disease of the main renal arteries and/or their branches. This disease essentially is characterized by atheromatous lesions in the renal arteries which compromise arterial renal blood flow. Clinically, patients with atherosclerotic nephropathy can present with refractory hypertension and renal insufficiency, acute renal failure after treatment with antihypertensive drugs and unexplained, slowly progressive renal failure with or without hypertension (elderly patients). Observations from uncontrolled studies indicate that both the progression of renal insufficiency and the control of hypertension can be influenced favorably in about 80% of the cases by a revascularization procedure (arterial anastomosis, percutaneous arterial dilatation). Patients with suspected atherosclerotic nephropathy should probably be evaluated invasively and considered candidates for a revascularization procedure. The benefits of these therapies compared to conservative management need, however, evaluation in a controlled, prospective clinical trial. PMID- 2218464 TI - [Dieulafoy's simple stomach ulcer: apropos of 5 cases]. AB - Dieulafoy's ulcer is a probably congenital arterial malformation which may produce severe upper gastrointestinal haemorrhage. It represents about 1% of all cases of acute upper gastrointestinal haemorrhage (3/249 in our department during 1989). We report 5 cases in whom haemostatic endoscopic treatment was successful and propose therefore that this therapy should be the initial treatment of choice. Surgical intervention should be considered only if endoscopic therapy fails. PMID- 2218465 TI - [Prognostic value of electroencephalography in non-traumatic comas]. AB - We recorded an EEG within the first few days of coma in 100 patients without history of trauma or drug intoxication, in 50 after cardiac arrest, and in 50 in coma of other, chiefly metabolic etiologies. The EEG findings were classified in 5 categories (I-V) in terms of increasing severity. We were especially interested in the question whether the degree of early EEG disturbances allows prognostic conclusions regarding the clinical fate of patients one month after the beginning of coma. It was found that very severe EEG changes (Grad IV-V) indicate a poor prognosis (death, persistent vegetative state or profound neurological deficits) in over 90% of coma both after cardiac arrest and of other etiologies. An EEG without very severe changes (grade I-III) does not allow definite prognostic conclusions. Depending on the etiology, recovery occurs in 10-33% of cases. The prognostic significance of certain EEG parameters can be summarized as follows: areactivity to external stimuli and the presence of an "alpha-coma" pattern are usually (but not necessarily) associated with a poor outcome. The same applies to coma patients with epileptiform patterns in the EEG and/or suffering from epileptic or myoclonic seizures. One-fourth of patients with triphasic EEG complexes recover completely. PMID- 2218466 TI - [Endoluminal sonography as a preoperative staging method in rectal carcinoma]. AB - The selection of an appropriate surgical procedure for primary rectal cancer depends on the degree of local invasion of the tumor and its location. Computed tomography allows better preoperative staging than is possible by clinical staging. Endoluminal sonography demonstrates the different layers of the rectal wall as described by TNM-staging. Comparison of preoperative ultrasound staging and postoperative histopathological staging gave an overall accuracy of 83% in all of our consecutive 63 prospectively examined patients. In 11% the tumor was overstaged and in 6% understaged. Comparing clinical staging, computed tomography and endoluminal sonography in all patients with palpable but not stenotic tumors, endoluminal sonography gave an accuracy of 89% compared with 71% with clinical staging and 78% with computed tomography. The results demonstrate the reliability of the new staging method in selecting the surgical procedure (local excision - resection/amputation) in tumors of the lower rectum. Promising results with endoluminal sonography are also reported in the follow-up of patients operated on for rectal cancer. PMID- 2218467 TI - [Asymptomatic microhematuria: follow-up in 39 patients]. AB - We have studied 39 patients with asymptomatic microhematuria (AM) over a mean period of 3.7 years (2.6 to 5.3). In 28 patients, the etiology of the AM had remained unknown despite extensive work-up at the time of AM diagnosis. During follow-up, the urine was examined by the dipstick method and a urine sediment was prepared by standard techniques. Erythrocyturia was judged as grade I or grade II (3-9 or less than 9 erythrocytes/hpf) and classified by phase-contrast microscopy as glomerular or non-glomerular (greater than 30% or less than 30% of erythrocytes with glomerular characteristics). The results were as follows. All patients were in good health during the whole follow-up. None developed significant proteinuria or gross hematuria. AM persisted in 28 of the 39 patients (72%) and in 22 of the 28 with AM of unknown etiology (79%). Persistence of AM was independent of grade and morphology of AM. Among the patients with AM of unknown cause, the fifteen who initially showed grade I AM had grade I AM in 92% and grade II AM in 8% of follow-up urinalyses, and the seven with grade II AM at the first examination had grade II AM in 65% and grade I AM in 35% of follow-up urinalyses (p = 0.007). The last morphologic classification of AM corresponded to the first in all patients with grade II AM, but only in 74% of patients with grade I AM. The following conclusions were drawn. (1) Most AM of unknown etiology persists over several years irrespective of grade and morphology of erythrocyturia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218468 TI - [Ventilatory function and bronchial responsiveness in army recruits]. AB - Lung function and determination of the bronchial responsiveness to methacholine were performed in two groups of Swiss army recruits aged 20 years (total 233), where 144 had respiratory complaints or a history of prior asthma and 89 were asymptomatic, among whom 26 had recently suffered from upper respiratory tract infection (URTI). A bronchial obstruction (ratio FEV1/FVC less than 73%) was observed among 6% of the subjects with symptoms, 6% of the asymptomatic control subjects and 4% in the group with recent URTI. The differences are not significant. A bronchial hyperresponsiveness (defined as PD20 less than 900 mcg) was observed in 45% of the symptomatic subjects (54% in 109 recruits complaining of dyspnea on exertion) against 3% in the control group (p less than 0.001) and 12% in the group with recent URTI (NS, p = 0.14). Among subjects complaining of dyspnea on exertion, more than half have an obvious bronchial hyperresponsiveness at a level usually observed in asthmatics, most of them without any clinical finding or permanent bronchial obstruction. Although the sensitivity of the determination of bronchial responsiveness is low (47%) its specificity is high (97%). The test allows detection of some subjects with asthma among young subjects complaining of respiratory troubles in spite of normal clinical examination and lung function. A normal level of bronchial responsiveness practically excludes asthma. PMID- 2218469 TI - [SAF--an alternative fixation solution for parasitological stool specimens]. AB - A comparative parasitological study in 3 collectives using 2 different fixatives for stool samples (SAF and MIF) was carried out. The SAF fixative consistently showed a significantly higher sensitivity for parasitic protozoa than the MIF fixative (Entamoeba histolytica 90.0% vs. 64.4%, Giardia lamblia 97.7% vs. 64.4%), which was due to an increased detection of cysts of both species. No difference in sensitivity for helminths was found. The cheap, simple formula and, due to the absence of mercury, the low toxicity are further advantages of the SAF fixative. Moreover, contrary to the MIF fixative, the SAF fixative permits the use of a wide range of staining techniques starting from fixed specimens. These results led to the replacement of the MIF fixative by the SAF fixative at the Diagnostic Center of the Swiss Tropical Institute. PMID- 2218470 TI - [Changes in the endometrium of the cow after intrauterine administration of different drugs]. AB - 32 young and healthy cows each received a single intrauterine treatment with one of the following solutions: Lugol's solution, Vetedine, Lorasol, Lotagen, Aureomycin, and normal saline solution as a control. Endometrial biopsies were taken immediately before application and at days 1, 3, 6, 10, 15, 20 and 30 thereafter. On day 1, degenerative and inflammatory reactions could already be observed in all groups, with the exception of the control group. The intensity of the lesions varied, not only between treatment groups but also to a lesser extent between individuals within groups. Degeneration and inflammatory reaction found in the subepithelial stromal tissues were more distinct than those seen in the epithelia. Lorasol caused the most severe degenerative changes, regarding the depth of degeneration into the tissue, as well as the intensity of the inflammatory reaction. Lugol's solution also showed a high degree of change, followed by Lotagen and Vetedine showing moderate change, respectively. Reaction to the antibiotic treatment with Aureomycin was only slight. The regeneration time of these lesions was proportional to the intensity of the induced changes, amounting to 10-15 days for Lorasol and 3-6 days for Aureomycin, respectively. The clinical significance of these findings is discussed. PMID- 2218471 TI - [Capillaria hepatica in a dog and a hedgehog]. AB - A liver infection with Capillaria hepatica is described, having been found for the first time in Switzerland in a dog and a hedgehog. After a literature review of cases known among man and animals, we present our own pathological findings. Furthermore, the parasite's life cycle is discussed. PMID- 2218472 TI - 10th autumn meeting of the European Society of Veterinary Pathology. Zurich, September 24-27, 1990. Abstracts. PMID- 2218473 TI - [The fight against doping: international and national efforts as exemplified by the Convention of the Council of Europe and the doping regulations of the Swiss National Association for Sports]. AB - The international and national efforts to flight doping in sports are shown by the examples of the Anti-Doping Convention of the Council of Europe and the regulations of the Swiss Association of Sports. Major efforts are made in the fields of education and information, search for and application of optimal methods for training and care as well as dope-controls at and out of competitions. The harmonization of the anti-doping regulations and the disciplinary procedures that have to follow the principles of natural justice are considered to be important. The Swiss regulations allow, at variance with international customs, to treat injured athletes therapeutically with doping substances. PMID- 2218474 TI - [Sports correlate with positive living habits. Results from the population survey the Swiss MONICA project]. AB - Exercise is associated with positive health habits: Findings from the populations survey of the Swiss MONICA-project. Relatively little is known on population-wide relations of habitual exercise to relevant health factors such as diet, cigarette smoking and overweight. Data from a population-based sample of approximately 800 men and women each, aged 25-64, collected in western Switzerland as a part of an international WHO-project, were used to examine cross-sectionally the interrelationships between different lifestyle factors. Men and women training regularly (i.e. greater than or equal to 2 times/wk) exhibited consistently and highly significantly more favourable health habits, regarding diet (i.e. trimming visible fat, higher intake of fruits, salad and vegetables, yogurt and cottage cheese), nonsmoking, and weight control. Men and women with at least some regular physical activity during leisure-time had in turn more favourable health habits than their sedentary counterparts. In both sexes, educational level was directly related to exercise and a healthy diet, and inversely related to smoking and relative weight. Regularly training men and women also had a significantly improved lipid profile compared to inactive ones. It is concluded from this study that leisure-time physical activity and exercise are related to a positive health behaviour including diet, nonsmoking and efficient weight control. This may suggest that exercise should possibly be integrated into any population-wide attempts and efforts to promote health to enhance primary prevention. PMID- 2218475 TI - [The radiological functional testing in fibular ligament lesions--a critical analysis and clinical study]. AB - Injuries to the lateral ligaments of the ankle require an accurate diagnosis, especially because most injuries to one ligament are not treated surgically any more. Different stress devices are in use for an objective and standardised assessment of the instability of the ankle joint. In a group of 76 patients with injuries to their lateral ligaments of the ankle we compared posttraumatic instability by radiological stress test as done by hand or by a Telos stress device. In 25 patients treated by surgery an additional intraoperative stress X ray (talar tilt) was performed. The results of the instability tests done by hand versus those obtained with a Telos stress device showed a poor correlation (r = 0.786). An analogous result was obtained by comparing the Telos device stress views to the intraoperative stress controls done by hand (r = 0.771). Only the pre- and intraoperative measurements by hand showed a good correlation (r = 0.958). The results are discussed with reference to a biomechanical model and recommendations for routine diagnosis are proposed. PMID- 2218476 TI - [The treatment of fibular ligament lesions using the Ortho-Rehab shoe]. AB - In a prospective study we examined 46 patients (14-49 years of age) with fresh ruptures of the lateral ligaments of the ankle (talar tilt greater than or equal to 10 degrees). Treatment consisted in six weeks of taping combined with wearing of a special rehabilitation shoe (Ortho Rehab). 28 patients were treated conservatively and 18 had an operative repair of their ruptured ligaments. After 8 weeks every patient was clinically controlled. Until now 35 patients were reevaluated more than one year after injury. Treatment was judged as very comfortable and positive. Working capacity was achieved after an average of 14.8 days and all patients returned to their former sports activity 3 to 8 weeks after the event. Mechanical and functional stability after more than one year are excellent with the exception of 3 cases. The results are discussed and compared with other studies. PMID- 2218477 TI - Big-time orphan. Human growth hormone could be a blockbuster. PMID- 2218478 TI - Skin stand-ins. Dermal substitutes promise to reduce animal testing. PMID- 2218479 TI - Anatomical cartography. Computer maps reveal the topography of arthritis. PMID- 2218480 TI - Molecular engineers mimic mother nature. PMID- 2218481 TI - Energy for planet Earth. PMID- 2218482 TI - Fetal law. Experimental surgery may feed ethical debates. PMID- 2218483 TI - Overview: tolerating self. Experience teaches the immune system to recognize the self. PMID- 2218484 TI - The Dirty Air Act. PMID- 2218485 TI - Asbestos policy. PMID- 2218486 TI - Mad cow disease: uncertainty rules. PMID- 2218487 TI - Female primatologists confer--without men. PMID- 2218488 TI - Will AIDS conference migrate? PMID- 2218489 TI - NIH urged to be a smart shopper. PMID- 2218490 TI - Genome center grants chosen. PMID- 2218491 TI - Voice lessons for psychotics. PMID- 2218492 TI - Partner found for the myc protein. PMID- 2218493 TI - Drug policy: striking the right balance. AB - Drug policy should strike the right balance between reducing the harm done by psychoactive drugs and reducing the harm that results from strict legal prohibitions and their enforcement. It is concluded, from a cost-benefit analysis based on pharmacologic, toxicologic, sociologic, and historical facts, that radical steps to repeal the prohibitions on presently illicit drugs would be likely, on balance, to make matters worse rather than better. Specific recommendations are offered for ameliorating the dangers to users and to society that are posed by each addictive drug. PMID- 2218494 TI - New methods of drug delivery. AB - Conventional forms of drug administration generally rely on pills, eye drops, ointments, and intravenous solutions. Recently, a number of novel drug delivery approaches have been developed. These approaches include drug modification by chemical means, drug entrapment in small vesicles that are injected into the bloodstream, and drug entrapment within pumps or polymeric materials that are placed in desired bodily compartments (for example, the eye or beneath the skin). These techniques have already led to delivery systems that improve human health, and continued research may revolutionize the way many drugs are delivered. PMID- 2218495 TI - Structural characterization of a partly folded apomyoglobin intermediate. AB - To understand why proteins adopt particular three-dimensional structures, it is important to elucidate the hierarchy of interactions that stabilize the native state. Proteins in partly folded states can be used to dissect protein organizational hierarchies. A partly folded apomyoglobin intermediate has now been characterized structurally by trapping slowly exchanging peptide NH protons and analyzing them by two-dimensional 1H-NMR (nuclear magnetic resonance). Protons in the A, G, and H helix regions are protected from exchange, while protons in the B and E helix regions exchange freely. On the basis of these results and the three-dimensional structure of native myoglobin, a structural model is presented for the partly folded intermediate in which a compact subdomain retains structure while the remainder of the protein is essentially unfolded. PMID- 2218497 TI - "Pure" human hematopoietic progenitors: permissive action of basic fibroblast growth factor. AB - Methodology has been developed that enables virtually complete purification and abundant recovery of early hematopoietic progenitors from normal human adult peripheral blood. A fraction of the pure progenitors is multipotent (generates mixed colonies) and exhibits self-renewal capacity (gives rise to blast cell colonies). This methodology provides a fundamental tool for basic and clinical studies on hematopoiesis. Optimal in vitro cloning of virtually pure progenitors requires not only the stimulatory effect of interleukin-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin, but also the permissive action of basic fibroblast growth factor. These findings suggest a regulatory role for this growth factor in early hematopoiesis. PMID- 2218496 TI - Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. AB - The erbB2 oncogene encodes a 185-kilodalton transmembrane protein whose sequence is similar to the epidermal growth factor receptor (EGFR). A 30-kilodalton factor (gp30) secreted from MDA-MB-231 human breast cancer cells was shown to be a ligand for p185erbB2. An antibody to EGFR abolished the tyrosine phosphorylation induced by EGF and transforming growth factor-alpha (TGF-alpha) but only partially blocked that produced by gp30 in SK-BR-3 breast cancer cells. In two cell lines that overexpress erbB2 but do not expresss EGFR (MDA-MB-453 breast cancer cells and a Chinese hamster ovary cell line that had been transfected with erbB2), phosphorylation of p185erbB2 was induced only by gp30. The gp30 specifically inhibited the growth of cells that overexpressed p185erbB2. An antibody to EGFR had no effect on the inhibition of SK-BR-3 cell colony formation obtained with gp30. Thus, it appeared that gp30 interacted directly with the EGFR and erbB2. Direct binding of gp30 to p185erbB2 was confirmed by binding competition experiments, where gp30 was found to displace the p185erbB2 binding of a specific antibody to p185erbB2. The evidence described here suggests that gp30 is a ligand for p185erbB2. PMID- 2218498 TI - Protection from chemotherapy-induced alopecia in a rat model. AB - Alopecia (hair loss) is among the most distressing side effects of cancer chemotherapy. Little progress has been made, however, in its prevention or treatment, partly because of the lack of suitable experimental model. In recent work on the treatment of myelogenous leukemia in the rat, the following observations were made: (i) treatment of 8-day-old rats with cytosine arabinoside consistently produced alopecia, and (ii) ImuVert, a biologic response modifier derived from the bacterium Serratia marcescens, uniformly produced complete protection against the alopecia. In subsequent experiments, both cyclophosphamide and doxorubicin also produced alopecia in this model, and the doxorubicin-induced alopecia was prevented by treatment with ImuVert. The potential relevance of these observations to chemotherapy-induced alopecia in the clinical setting should be examined. PMID- 2218499 TI - Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer. AB - The proliferative potential of human diploid endothelial cells is finite, and cellular senescence in vitro is accompanied by the failure of the endothelial cell to respond to exogenous growth factors. Senescent human endothelial cells were shown to contain high amounts of the transcript for the cytokine interleukin 1 alpha (IL-1 alpha), a potent inhibitor of endothelial cell proliferation in vitro. In contrast, transformed human endothelial cells did not contain detectable IL-1 alpha messenger RNA. Treatment of human endothelial cell populations with an antisense oligodeoxynucleotide to the human IL-1 alpha transcript prevented cell senescence and extended the proliferative life-span of the cells in vitro. Removal of the IL-1 alpha antisense oligomer resulted in the generation of the senescent phenotype and loss of proliferative potential. These data suggest that human endothelial cell senescence in vitro is a dynamic process regulated by the potential intracellular activity of IL-1 alpha. PMID- 2218500 TI - Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. AB - Acute promyelocytic leukemia (APL; FAB M3) is characterized by a predominance of malignant promyelocytes that carry a reciprocal translocation between the long arms of chromosomes 15 and 17, t(15;17) (q22;q11.2-q12). This translocation has become diagnostic for APL, as it is present in almost 100 percent of cases. A Not I linking clone was used to detect this translocation initially on pulsed-field gel electrophoresis and subsequently with conventional Southern (DNA) analysis. The breakpoints in ten APL cases examined were shown to cluster in a 12-kb region of chromosome 17, containing two CpG-rich islands. The region is the first intron of the retinoic acid receptor alpha gene (RARA). PMID- 2218501 TI - Different tumor-derived p53 mutants exhibit distinct biological activities. AB - In its wild-type form, the protein p53 can interfere with neoplastic processes. Tumor-derived cells often express mutant p53. Full-length mutant forms of p53 isolated so far from transformed mouse cells exhibit three common properties in vitro: loss of transformation-suppressing activity, gain of pronounced transforming potential, and ability to bind the heat shock protein cognate hsc70. A tumor-derived mouse p53 variant is now described, whose site of mutation corresponds to a hot spot for p53 in human tumors. While absolutely nonsuppressing, it is only weakly transforming and exhibits no detectable hsc70 binding. The data suggest that the ability of a p53 mutant to bind endogenous p53 is not the sole determinant of its oncogenic potential. The data also support the existence of gain-of-function p53 mutants. PMID- 2218502 TI - Impact of mass treatment of onchocerciasis with ivermectin on the transmission of infection. AB - Onchocerciasis is a major blinding disease that, until recently, has been essentially untreatable. Ivermectin is a safe and effective drug for the mass treatment of onchocerciasis and when used on an individual basis, it reduces the ability of the treated person to transmit Onchocerca volvulus infection. In the present study, the effect of community-based ivermectin treatment on the degree of transmission within the community was assessed by determining the incidence of new infection in children. Ivermectin was distributed annually on three occasions to the eligible members of a population of approximately 14,000 people living on a rubber plantation in a forest area endemic for onchocerciasis. After 2 years, the prevalence of infection in 5-year-old children decreased by 21%. The annual incidence in an uninfected cohort of children decreased by 35% and, after age specific adjustment, the reduction in incidence in 7- to 12-year-old children was 45%. Thus, community-based distribution of ivermectin led to a significant reduction in incidence of new infection. These findings suggest that ivermectin can be important in reducing the transmission of onchocerciasis. PMID- 2218503 TI - Extrageniculate vision in hemianopic humans: saccade inhibition by signals in the blind field. AB - The functional competence of extrageniculate visual pathways in hemianopic humans was demonstrated by showing that distractor signals in the blind half of the visual field could inhibit saccades toward targets in the intact visual field. This inhibitory effect of unseen distractors in patients occurred only when distractors were presented in the temporal half of the visual field, was specific to oculomotor responses, and did not occur in normal subjects. These results show that a peripheral visual signal activates retinotectal pathways to prime the oculomotor system and that these pathways can mediate orienting behavior in hemianopic humans. PMID- 2218505 TI - Inhibition of HIV-1 infectivity by phosphate-methylated DNA: retraction. PMID- 2218504 TI - Rhodopsin mutants that bind but fail to activate transducin. AB - Rhodopsin is a member of a family of receptors that contain seven transmembrane helices and are coupled to G proteins. The nature of the interactions between rhodopsin mutants and the G protein, transduction (Gt), was investigated by flash photolysis in order to monitor directly Gt binding and dissociation. Three mutant opsins with alterations in their cytoplasmic loops bound 11-cis-retinal to yield pigments with native rhodopsin absorption spectra, but they failed to stimulate the guanosine triphosphatase activity of Gt. The opsin mutations included reversal of a charged pair conserved in all G protein-coupled receptors at the cytoplasmic border of the third transmembrane helix (mutant CD1), replacement of 13 amino acids in the second cytoplasmic loop (mutant CD2), and deletion of 13 amino acids from the third cytoplasmic loop (mutant EF1). Whereas mutant CD1 failed to bind Gt, mutants CD2 and EF1 showed normal Gt binding but failed to release Gt in the presence of guanosine triphosphate. Therefore, it appears that at least the second and third cytoplasmic loops of rhodopsin are required for activation of bound Gt. PMID- 2218506 TI - Human habitation of the Americas. PMID- 2218507 TI - Cetus's costly stumble on IL-2. PMID- 2218508 TI - Institute of Medicine backs training over research. PMID- 2218509 TI - Flying blind: the making of EMF policy. PMID- 2218510 TI - More mice on the way, thanks to NIH. PMID- 2218511 TI - Still flying blind in the war on drugs. PMID- 2218512 TI - Embryology gets down--to the molecular level. PMID- 2218513 TI - Zebrafish: swimming into the development mainstream. PMID- 2218514 TI - Functional magnetic resonance imaging in medicine and physiology. AB - Magnetic resonance imaging (MRI) is a well-established diagnostic tool that provides detailed information about macroscopic structure and anatomy. Recent advances in MRI allow the noninvasive spatial evaluation of various biophysical and biochemical processes in living systems. Specifically, the motion of water can be measured in processes such as vascular flow, capillary flow, diffusion, and exchange. In addition, the concentrations of various metabolites can be determined for the assessment of regional regulation of metabolism. Examples are given that demonstrate the use of functional MRI for clinical and research purposes. This development adds a new dimension to the application of magnetic resonance to medicine and physiology. PMID- 2218515 TI - Chromosomal region of the cystic fibrosis gene in yeast artificial chromosomes: a model for human genome mapping. AB - A general strategy for cloning and mapping large regions of human DNA with yeast artificial chromosomes (YAC's) is described. It relies on the use of the polymerase chain reaction to detect DNA landmarks called sequence-tagged sites (STS's) within YAC clones. The method was applied to the region of human chromosome 7 containing the cystic fibrosis (CF) gene. Thirty YAC clones from this region were analyzed, and a contig map that spans more than 1,500,000 base pairs was assembled. Individual YAC's as large as 790 kilobase pairs and containing the entire CF gene were constructed in vivo by meiotic recombination in yeast between pairs of overlapping YAC's. PMID- 2218516 TI - The human genome map 1990. PMID- 2218518 TI - African AIDS: whose research rules? PMID- 2218517 TI - Genetics of small populations. PMID- 2218519 TI - OTA quietly backs fetal tissue work. PMID- 2218520 TI - Gallo inquiry takes puzzling new turn. PMID- 2218521 TI - Tobacco industry does slow burn over EPA adviser. PMID- 2218522 TI - Celebrating the leech. PMID- 2218523 TI - NIH watch. PMID- 2218524 TI - The high culture of neuroscience. PMID- 2218525 TI - Mapping terra incognita (humani corporis) PMID- 2218526 TI - Sources of human psychological differences: the Minnesota Study of Twins Reared Apart. AB - Since 1979, a continuing study of monozygotic and dizygotic twins, separated in infancy and reared apart, has subjected more than 100 sets of reared-apart twins or triplets to a week of intensive psychological and physiological assessment. Like the prior, smaller studies of monozygotic twins reared apart, about 70% of the variance in IQ was found to be associated with genetic variation. On multiple measures of personality and temperament, occupational and leisure-time interests, and social attitudes, monozygotic twins reared apart are about as similar as are monozygotic twins reared together. These findings extend and support those from numerous other twin, family, and adoption studies. It is a plausible hypothesis that genetic differences affect psychological differences largely indirectly, by influencing the effective environment of the developing child. This evidence for the strong heritability of most psychological traits, sensibly construed, does not detract from the value or importance of parenting, education, and other propaedeutic interventions. PMID- 2218527 TI - Mapping the human genome: current status. AB - The human genome has already been the subject of extensive research activity even though the Human Genome Project is only just officially starting. This review and the accompanying wall chart attempt to provide an integrated, quantitative, and detailed summary of the status of knowledge on the human genome in mid-1990. The analysis has highlighted the rudimentary nature of many of the information links needed for the task. While this overview could not be fully comprehensive and required simplifying assumptions, the results have provided estimates of relative progress on a region-by-region basis throughout the genome. PMID- 2218528 TI - Radiation hybrid mapping: a somatic cell genetic method for constructing high resolution maps of mammalian chromosomes. AB - Radiation hybrid (RH) mapping, a somatic cell genetic technique, was developed as a general approach for constructing long-range maps of mammalian chromosomes. This statistical method depends on x-ray breakage of chromosomes to determine the distances between DNA markers, as well as their order on the chromosome. In addition, the method allows the relative likelihoods of alternative marker orders to be determined. The RH procedure was used to map 14 DNA probes from a region of human chromosome 21 spanning 20 megabase pairs. The map was confirmed by pulsed field gel electrophoretic analysis. The results demonstrate the effectiveness of RH mapping for constructing high-resolution, contiguous maps of mammalian chromosomes. PMID- 2218529 TI - Cleaving yeast and Escherichia coli genomes at a single site. AB - The 15-megabase pair Saccharomyces cerevisiae and the 4.7-megabase pair Escherichia coli genomes were completely cleaved at a single predetermined site by means of the Achilles' heel cleavage (AC) procedure. The symmetric lac operator (lacOs) was introduced into the circular Escherichia coli genome and into one of the 16 yeast chromosomes. Intact chromosomes from the resulting strains were prepared in agarose microbeads and methylated with Hha I (5'-GCGC) methyltransferase (M.Hha I) in the presence of lac repressor (LacI). All Hae II sites (5'-[sequence: see text]) with the exception of the one in lacOs, which was protected by LacI, were modified and thus no longer recognized by Hae II. After inactivation of M.Hha I and LacI, Hae II was used to completely cleave the chromosomes specifically at the inserted lacOs. These experiments demonstrate the feasibility of using the AC approach to efficiently extend the specificity of naturally occurring restriction enzymes and create new tools for the mapping and precise molecular dissection of multimegabase genomes. PMID- 2218530 TI - Mutations affecting TEA blockade and ion permeation in voltage-activated K+ channels. AB - Voltage-dependent ion channels are responsible for electrical signaling in neurons and other cells. The main classes of voltage-dependent channels (sodium-, calcium-, and potassium-selective channels) have closely related molecular structures. For one member of this superfamily, the transiently voltage-activated Shaker H4 potassium channel, specific amino acid residues have now been identified that affect channel blockade by the small ion tetraethylammonium, as well as the conduction of ions through the pore. Furthermore, variation at one of these amino acid positions among naturally occurring potassium channels may account for most of their differences in sensitivity to tetraethylammonium. PMID- 2218531 TI - Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. AB - The amyloid beta protein is deposited in the brains of patients with Alzheimer's disease but its pathogenic role is unknown. In culture, the amyloid beta protein was neurotrophic to undifferentiated hippocampal neurons at low concentrations and neurotoxic to mature neurons at higher concentrations. In differentiated neurons, amyloid beta protein caused dendritic and axonal retraction followed by neuronal death. A portion of the amyloid beta protein (amino acids 25 to 35) mediated both the trophic and toxic effects and was homologous to the tachykinin neuropeptide family. The effects of the amyloid beta protein were mimicked by tachykinin antagonists and completely reversed by specific tachykinin agonists. Thus, the amyloid beta protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration. PMID- 2218532 TI - In vitro reconstruction of the respiratory central pattern generator of the mollusk Lymnaea. AB - Most rhythmic behaviors such as respiration, locomotion, and feeding are under the control of networks of neurons in the central nervous system known as central pattern generators (CPGs). The respiratory rhythm of the pond snail Lymnaea stagnalis is a relatively simple, CPG-based behavior for which the underlying neural elements have been identified. A three-neuron network capable of generating the respiratory rhythm of this air-breathing mollusk has been reconstructed in culture. The intrinsic and network properties of this neural ensemble have been studied, and the mechanism of postinhibitory rebound excitation was found to be important for the rhythm generation. This in vitro model system enables a better understanding of the neural basis of rhythm generation. PMID- 2218533 TI - A magnesium current in Paramecium. AB - Recent reappraisals of the role of ionized magnesium in cell function suggest that many cells maintain intracellular free Mg2+ at low concentrations (0.1 to 0.7 mM) and that external agents can influence cell function via changes in intracellular Mg2+ concentration. Depolarization and hyperpolarization of voltage clamped Paramecium elicited a Mg2(+)-specific current, IMg. Both Co2+ and Mn2+ were able to substitute for Mg2+ as charge carriers, but the resultant currents were reduced compared with Mg2+ currents. Intracellular free Mg2+ concentrations were estimated from the reversal potential of IMg to be about 0.39 mM. The IMg was inhibited when external Ca2+ was removed or a Ca2+ chelator was injected, suggesting that its activation was Ca2(+)-dependent. PMID- 2218534 TI - The primate hippocampal formation: evidence for a time-limited role in memory storage. AB - Clinical and experimental studies have shown that the hippocampal formation and related structures in the medial temporal lobe are important for learning and memory. Retrograde amnesia was studied prospectively in monkeys to understand the contribution of the hippocampal formation to memory function. Monkeys learned to discriminate 100 pairs of objects beginning 16, 12, 8, 4, and 2 weeks before the hippocampal formation was removed (20 different pairs at each time period). Two weeks after surgery, memory was assessed by presenting each of the 100 object pairs again for a single-choice trial. Normal monkeys exhibited forgetting; that is, they remembered recently learned objects better than objects learned many weeks earlier. Monkeys with hippocampal damage were severely impaired at remembering recently learned objects. In addition, they remembered objects learned long ago as well as normal monkeys did and significantly better than they remembered objects learned recently. These results show that the hippocampal formation is required for memory storage for only a limited period of time after learning. As time passes, its role in memory diminishes, and a more permanent memory gradually develops independently of the hippocampal formation, probably in neocortex. PMID- 2218535 TI - The meaning of hydrophobicity. PMID- 2218536 TI - Uncertainties about health effects of radon. PMID- 2218537 TI - Chloral hydrate warning. PMID- 2218538 TI - Biotechnology, human disease, and the FDA. PMID- 2218539 TI - Which patient did Gallo's virus come from? PMID- 2218540 TI - Judd leaves NIMH. PMID- 2218541 TI - The embryo takes its vitamins. PMID- 2218542 TI - Our chimp cousins get that much closer. PMID- 2218543 TI - Overcoming rejection to win a Nobel Prize. PMID- 2218544 TI - The drug dilemma: manipulating the demand. AB - Drug abuse in the United States has posed a dilemma during most of this century. Intemperate use of reinforcing drugs is hazardous to health and safety, but strict prohibition fosters an illicit market with criminal effects that may be equally harmful. The crux of the problem is the willingness of millions of people to risk toxicity and arrest to gain psychopharmacological rewards. Cocaine is the present source of most concern. Recommendations for reducing demand and abuse are given, including the implementation of preventive techniques, the investigation of various treatments, the use of modern chemical and electronic technology, and the development of new pharmacological alternatives. PMID- 2218546 TI - "Rock fever" on Majuro. PMID- 2218545 TI - Transport and storage of vitamin A. AB - The requirement of vitamin A (retinoids) for vision has been recognized for decades. In addition, vitamin A is involved in fetal development and in the regulation of proliferation and differentiation of cells throughout life. This fat-soluble organic compound cannot be synthesized endogenously by humans and thus is an essential nutrient; a well-regulated transport and storage system provides tissues with the correct amounts of retinoids in spite of normal fluctuations in daily vitamin A intake. An overview is presented here of current knowledge and hypotheses about the absorption, transport, storage, and metabolism of vitamin A. Some information is also presented about a group of ligand dependent transcription factors, the retinoic acid receptors, that apparently mediate many of the extravisual effects of retinoids. PMID- 2218547 TI - Assisting with developmental task achievement of the hospitalized adolescent. PMID- 2218548 TI - Rural health care in America: future directions. Testimony on the future of rural health care. PMID- 2218549 TI - Anatomy and physiology of the cervical spine. AB - Although the lumbar spine was extensively studied from 1934 to the present, the cervical spine has received far less attention. Anatomic, physiological, biochemical, and biomechanical characteristics of the lumbar spine are often presumed to apply to the cervical spine. The differences are far too extensive to warrant such an assumed correlation. Beginning in 1955, the authors have collected 171 whole human spines and studied them anatomically, physiologically, and histologically. Reported in this article are clinically important anatomic characteristics of the nucleus pulposus, the uncinate process, nerve root exit sites, position of the motor (anterior) nerve root, relation of spinal cord volume to size and shape of the spinal canal, anatomy of the anterior and posterior spinal canal, menisci of the zygapophyseal joints, and the anatomy and clinical significance of the autonomic nervous system in the cervical spine. PMID- 2218550 TI - Panoramic nailfold capillaroscopy: a new reading method and normal range. AB - Current interpretation of nailfold capillaroscopy is largely based on qualitative and subjective parameters. These parameters make the accurate assessment of the extent of the nailfold microangiopathy difficult. The authors present a comprehensive method in which several quantitative or semiquantitative parameters are used to assess the main microangiopathic features, such as microhemorrhage, plexus visibility, devascularization, and morphologic anomalies of the end row loops. The method is checked for reproducibility and applied to a sample of 800 healthy people to establish the normal range. The influences of extrinsic variables, such as gender, ethnicity, age, and local nailfold conditions are also included. PMID- 2218551 TI - Therapeutic exercise for rheumatoid arthritis and osteoarthritis. AB - Therapeutic exercise in rheumatoid arthritis and osteoarthritis may be useful in improving aerobic capacity, strengthening muscles, improving endurance and increasing flexibility. This article reviews the major studies of exercise in these conditions and summarizes the authors recommendations regarding the use of therapeutic exercise in the treatment of rheumatoid arthritis osteoarthritis. PMID- 2218552 TI - Iliopsoas bursitis: clinical features, radiographic findings, and disease associations. AB - Inflammation of the iliopsoas bursa is a common manifestation of a wide array of inflammatory, degenerative, and traumatic musculoskeletal conditions. The clinical presentation of iliopsoas bursitis is variable, and includes pain, mass lesion, or compression syndromes of the inguinal compartment. Affected individuals frequently have underlying synovitis of the hip or a history of occupational or recreational injury. Early and accurate diagnosis is facilitated by appropriate radiographic studies. PMID- 2218553 TI - A long-term study of interstitial lung disease in systemic lupus erythematosus. AB - The clinical course of chronic diffuse interstitial lung disease (ILD) was studied in 14 patients with SLE. The mean duration of follow-up was 7.3 years. All patients had dyspnea on exertion, pleuritic chest pain, chronic cough, and basilar rales. Chest roentgenogram showed diffuse or basilar infiltrates, pleural disease, and elevation of both diaphragms. Systemic corticosteroids were given early in the course of the illness for lung involvement and multisystem disease. Diffusing capacity for carbon monoxide (DLCO) and inspiratory vital capacity (IVC) improved or remained unchanged in the majority of patients. Respiratory complaints improved in all patients; however, two patients died of pulmonary fibrosis and another died of bacterial pneumonia. Alveolar septal deposits of immunoglobulins and complement were found. This study showed that while variability existed among individual subjects, the clinical progression of ILD was slow and tended to improve or stabilize with time. PMID- 2218554 TI - Renal disorders in rheumatoid arthritis. AB - Renal disorders are a frequent cause of death in patients with rheumatoid arthritis (RA), but are less apparent in living RA patients. In part, this may be because of insensitive screening methods. In this review, some of the relations among renal pathology, renal function, and antirheumatic therapy are clarified. A classification of renal disorders according to etiology is proposed. Two categories of disorders are distinguished: those related to RA and its complications, and those related to drug therapy. The disorders belonging to these categories are reviewed. Finally, a case is made for the existence of a third category, "RA nephropathy." It is hypothesized that this mild and nonspecific nephropathy is the result of cumulative minor insults caused by the disease and its therapy. The presence of such a "subclinical" nephropathy would explain the greater sensitivity of RA patients to other renal insults, and the high prevalence of renal failure at death. PMID- 2218555 TI - [Dorsal plate osteosynthesis of the tibial shaft. Results of a collective study of the German section of the International AO (Study Group for Osteosynthesis Problems)]. AB - This collective study was conducted by the German section of AO International to work out the indications for fixation of the tibial shaft by means of dorsal plating. Primary dorsal plating was done in 70 cases. Most of the patients had second- or third-degree open fractures with severe ventral soft tissue injuries or closed fractures that could not be reduced and fixed conservatively. In 72 patients, secondary dorsal plate fixation was performed. The main reason for the dorsally positioned plate was persistent instability or axial malalignment after previous external or internal fixation, but failed conservative treatment constituted a further reason. Most of these patients had such severe damage following fractures that dorsal plating was the last chance of avoiding amputation. The high rate of complications (12 infections and 7 non-unions and breakages of implants after primary dorsal plating; 20 infections and 11 non unions and breakages of implants after secondary dorsal plating) has to be considered in the light of the extraordinary indications for the dorsal plating of the tibial shaft in especially severe fractures or disastrous sequelae. In cases with extremely severe conditions before fixation, dorsal plating of the tibial shaft for secondary operative treatment yields adequate results. PMID- 2218557 TI - [Biomechanical model calculations on the influence exerted by the sagittal sliding profile on patello-femoral load]. AB - Patellofemoral loads are calculated by means of a mathematical model based upon an elliptical approximation of the articulating profile. Differences in the sagittal curvature of morphological and arthroplastic gliding surfaces can be approximated by a differing eccentricity of the ellipse. The joint is balanced in a static situation by two tension forces. The resultant is the vector sum of both forces and represents the entire load. Small loads in the initial flexion of the knee joint and high loads in the end of flexion are caused by a flat sagittal curve. A more eccentric shape of the articulating profile reduces the loads at the end of flexion, because the quadriceps tendon starts to turn around the femur earlier. The model also takes into account the patellar ligament turning around the proximal tibia at wide flexion angles. Besides the design of the prosthesis, patellofemoral loads depend on the height of implantation of the femoral component. It must be borne in mind that forces will vary in magnitude at different flexion angles; the patient's activities after the operation must also be considered. PMID- 2218556 TI - [Comparative studies on the ingrowth behavior and the bone adhesion of various implant materials. An animal experiment]. AB - Each of 36 mongrel dogs received implants of the following six materials: methyl methacrylate, carbon fibre composite, aluminium oxide-ceramic, titanium alloy, pure titanium and hydroxylapatite (HA). Test rods 7 mm in diameter were used to perform a push-out test, and discs with a diameter of 25 mm and a thickness of 5 mm were used for a plane traction test. The animals got a fluorochrome labelling and were harvested 8 weeks after operation. The results of the push-out test were a stability of 3.6 N/mm2 for HA and very low values for all the other materials, while the plane tension test showed a stability of 1.6 N/mm2 for the HA discs and values that were not even measurable for all the other materials. The interface of HA and the bone could not be separated by mechanical forces; usually the bone or the ceramic material fractured beneath the interface, so that the real stability of the interface must be rated very high. Light and fluorescence microscopy revealed a close bone connection for HA and only partial connections for the other materials. HA-coated materials may have a future in orthopaedics surgery. PMID- 2218558 TI - [Significance and mechanism of thoracic and lumbar spine injuries in traffic accidents]. AB - An analysis of 96 persons who sustained injuries to dorsal and lumbar vertebrae during traffic accidents, established that spinal injuries (sustained by 3.8% of the 96 persons) are quite rare. Pedestrians, the elderly, and polytraumatized persons with extensive head injuries as accompanying trauma following particularly serious accidents are at especially high risk. The most frequent spinal injuries are compression fractures, which especially often give rise to the injury pattern found in the spine of motorcycle riders, pedestrians, and car passengers not wearing seat belts. In these cases a so-called "pushing-further" mechanism is quite often assumed as the biomechanical cause. In comparison, ruptures of the transverse process have often been established for car passengers wearing seat belts, which can be attributed causally to a psoas effect resulting from an overstretching movement of the body and muscular strain. Basically three different biomechanical movement patterns were established in this study: sliding mechanism, shearing effect and psoas effect; which of these is are involved depends on the capacity in which the person affected takes part in street traffic. All the spinal fractures examined can be classed as trauma sustained while travelling at high speed. They are not observed following collisions at low or moderate speed. PMID- 2218559 TI - [Quantitative immunohistological analysis of cell-mediated immunity in osteomyelitic bone tissue]. AB - The present investigation allows an exact identification and quantification of cell populations involved in local cell-mediated immunity of osteomyelitic bone tissue. Determinations of systemic immunity carried out in osteomyelitis patients indicated the distribution of immunogenic cells in the osteomyelitic focus only indirectly. The method described combined with simultaneous determination of the systemic immunity and cell mediators can lead to a quantitative description of cell-mediated immunity and in turn to a better understanding of the interaction of cells and transmitters involved in osteomyelitis. PMID- 2218560 TI - [Dislocation-fracture of the cunei-navicular joint line. Clinical aspects, pathomechanism and therapeutic concept in a very rare foot injury]. AB - Fracture dislocations of the cunei-navicular joints are a very rare type of intertarsal dislocation and most people are probably unfamiliar with this entity. Clinical, radiological and pathological aspects allow discrimination of such injuries from the dislocations in Lisfranc's and Chopart's articulation. We have seen one patient who was found to have a crush fracture of the cuneiforme mediale on one side and a fracture disruption with dorsal dislocation of the first and second metatarsals and of the medial and intermediate cuneiform bones on the other. According to the principles of treatment for other tarsal injuries, we carried out open reduction with joint debridement, reconstruction of ligaments and internal stabilization with transfixation screws. PMID- 2218561 TI - Chemotherapy for invasive bladder cancer: introduction. PMID- 2218562 TI - Neoadjuvant treatment of invasive bladder cancer. PMID- 2218564 TI - Pathology of bladder cancer: assessment of prognostic variables and response to therapy. PMID- 2218563 TI - Staging of bladder cancer: is the tumor, node, metastasis system adequate? PMID- 2218565 TI - Biological markers of prognosis in invasive bladder cancer. PMID- 2218566 TI - Imaging of invasive bladder cancer. PMID- 2218567 TI - Invasive bladder cancer: selection of primary treatment. PMID- 2218568 TI - Chemotherapy for invasive bladder cancer: neoadjuvant versus adjuvant. AB - The treatment of a patient with an invasive bladder tumor is based on the original urologic assessment. The global recommendation of a single treatment plan such as radical surgery, chemotherapy, radiation, or variations thereof, for all patients is clearly an antiquated approach. Case selection criteria for each single or multimodality approach need to be defined. Neoadjuvant therapy has the advantage of an in vivo response evaluation and the potential for bladder preservation. However, before treatment, the therapeutic goal--bladder preservation, treatment of micrometastases, or both--should be outlined. Patients with T2 or T3a tumors can be considered for bladder salvage by chemotherapy alone, chemotherapy plus radiation therapy or, chemotherapy followed by partial cystectomy. For those with higher stage tumors, therapy is directed more to the treatment of micrometastases, with bladder preservation as a secondary goal. In most cases additional therapy directed at the primary is required and clinical understaging remains significant. For some patients, initial surgery with the definition of the prognosis on firm pathologic grounds, may represent a better strategy. Those with positive nodes should be offered chemotherapy in the postoperative setting. Refinements in the techniques of ileo neo-bladders are of importance in improving quality of life, but when used alone will not alter the natural history of the disease. Drug resistance remains a major therapeutic obstacle. More effective agents, and the prospective identification of intrinsic or acquired resistance, invasion, and metastatic potential are required to optimize therapy for an individual patient. Ultimately, large scale randomized trials will be required to negate the heterogeneity of this patient population. Only then will individualization of treatment be possible. PMID- 2218569 TI - The role of radiation therapy alone or as an adjunct to surgery in bladder carcinoma. PMID- 2218570 TI - Radiotherapy combined with chemotherapy in treatment of muscle-invasive bladder carcinoma. PMID- 2218571 TI - Surgery of invasive bladder cancer: is pathologic staging necessary? PMID- 2218573 TI - Restaging procedures, criteria of response, and relationship between pathological response and survival. AB - The first priorities for upfront chemotherapy in TCCB are to prove in randomized phase III trials that the addition of toxic chemotherapy to toxic standard locoregional treatment can improve survival and/or permit bladder preservation. If such proof is obtained, we will need to distinguish patients who benefit from chemotherapy from those who do not. One way to make such a distinction is to separate responders from nonresponders. The prognostic value of downstaging to P0 or noninvasive cancer is significantly different from the prognosis associated with the continued presence of invasive disease. The available data regarding clinical assessment of response still appear to indicate that only the demonstration of a lack of response (see Table 2: cIR, cSD, cPD, greater than or equal to cT2) is reliable, However, there may be some patients, who after two courses of chemotherapy, still show the presence of invasive bladder cancer together with signs of tumor cell kill and may be further downstaged to P0 during the next two courses of chemotherapy. The clinical assessment of cCR and cPR is too inaccurate to be used as a basis for decisions concerning continuation of chemotherapy or bladder preservation. The decision to leave the bladder untreated after a cCR carries the risk of jeopardizing cure. More studies on the evaluation of response of the primary tumor are needed, probably with a central role for the pathologist to evaluate not only the gross presence, minimal residual disease, or true absence of cancer but also the adequacy of site and deepness of the restaging TUR biopsy. PMID- 2218572 TI - Neobladders: clinical management and considerations for patients receiving chemotherapy. AB - Continent catheterizable urinary reservoirs and orthotopic bladder substitutes are complex surgical endeavors. The goal is preservation of renal function, reliable continence, and storage intervals acceptable to the patient. The construction requires familiarity with bowel segments and may increase operative time for radical cystoprostatectomy by 30% to 50%. Patients with continent reservoirs have improved body image, work habits, and sexual and interpersonal relationships. Experience with patients with dysfunctional neurogenic bladders previously converted to Bricker urostomies now undiverted to continent reservoirs indicates an overall increase in physical activity and self-satisfaction. These patients are tolerant of reoperations to maintain independence from wet urostomies. Undoubtedly, the expectations of bladder cancer patients will differ from those of young adults with neurogenic bladder, but we have found that when all options are presented patients will seek out therapy that least alters their body image. Therefore, patient selection becomes an important factor in determining the success of continent reservoirs. Patients must have the dexterity and motivation to catheterize the urinary reservoir, irrigate for mucus and, in cases of orthotopic bladder replacement to urethra, accept the need for artificial sphincter placement in 30% to 40% of cases. Management of the neo bladders requires additional consideration of several practical and theoretic points for both the surgeon and medical oncologist: 1. Patients with diffuse carcinoma in situ or transitional cell carcinoma at the bladder neck or prostatic urethra should undergo simultaneous urethrectomy excluding orthotopic bladder replacement. 2. Ten percent to 40% of patients undergoing radical cystoprostatectomy for transitional cell cancer will have concomitant underdiagnosed adenocarcinoma of the prostate; patient prognosis will remain defined by the stage and grade of the bladder cancer. 3. Patients may have a tendency toward dehydration because of increased loss of free water through bowel transit. 4. Absorption of chloride, ammonium, and hydrogen ions may cause hyperchloremic acidosis, especially in face of imparied renal function. 5. Because of the potential for drug absorption across reservoir mucosa, patients receiving chemotherapy may require Foley catheterization with irrigation in addition to intravenous hydration. 6. Creatinine clearance is unsuitable for studying the renal function of reservoir patients because urine passes through the intestinal segment where creatinine is absorbed; glomerular filtration is better estimated by nuclear scanning with the reservoir emptied. 7. Most reservoirs will remain colonized with bacteria. 8. Antibiotic prophylaxis for the patient with temporary impairment of immune function during chemotherapy may be necessary. 9. Mucus may entrap bacteria serving as a host defense; its production may diminish with time from construction. All patients should be capable of performing reservoir irrigations to manage mucus obstruction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2218574 TI - Preemptive (neoadjuvant) chemotherapy: can analysis of eligibility criteria, prognostic factors, and tumor staging from different trials provide valid or useful comparisons? PMID- 2218575 TI - Endpoints of clinical trials in invasive bladder cancer. PMID- 2218576 TI - Can we combine available data to evaluate the effects of neoadjuvant chemotherapy for invasive bladder cancer? PMID- 2218578 TI - Current management of gallstones. PMID- 2218577 TI - Neoadjuvant chemotherapy for invasive bladder cancer: future directions. PMID- 2218579 TI - Epidemiology and natural history of gallstone disease. PMID- 2218580 TI - Pathophysiology and pathogenesis of cholesterol gallstone formation. PMID- 2218581 TI - Pigment gallstone pathogenesis: from man to molecules. PMID- 2218582 TI - Oral dissolution treatment of gallstones with bile acids. PMID- 2218583 TI - Topical dissolution treatment of cholesterol gallstones with methyl tert-butyl ether. PMID- 2218585 TI - Role of surgery in the management of gallstones. PMID- 2218584 TI - Extracorporeal shock-wave lithotripsy of gallstones with the adjuvant use of cholelitholytic bile acids. PMID- 2218586 TI - Magnetic resonance imaging of knee trauma. AB - This article reviews the magnetic resonance (MR) appearance of normal knee anatomy and the role of MRI in the evaluation of knee trauma. Images acquired in the sagittal plane are the most useful. A combination of T1- and T2-weighted spin echo pulse sequences is most commonly employed. A meniscal tear is identified by an intrameniscal signal which extends to the joint surface. MR and arthroscopic findings agree in more than 90% of patients. It is important to be familiar with the MRI appearance of normal anatomic variants that may be confused with meniscal tears: the transverse geniculate ligament, the hiatus of the popliteal tendon sheath, and the meniscofemoral ligaments. Tears in the anterior cruciate, posterior cruciate, and collateral ligaments are also depicted. PMID- 2218587 TI - Paget's disease of the patella. AB - Five patients with Paget's disease involving the patella were evaluated for the following radiographic features: trabecular pattern, cortical integrity, density, and size of the affected patella. Radiographic appearances consisted of minimal trabecular coarsening in the patella of nearly normal size and progressed to considerable cortical thickening and osteoblastic remodeling in a dramatically enlarged patella. The radiologic features of Paget's disease of the patella are distinctive and should obviate biopsy. PMID- 2218589 TI - Osteochondrosis dissecans of the glenoid. AB - Osteochondrosis dissecans of the glenoid is a rare condition that has been mentioned only once in the literature, by Lavner in 1947. Trauma is generally accepted as a cause of this disorder. Injury produces an ischemic insult to the subchondral bone and possible loose body formation if fragmentation of the articular surface occurs. Endocrine abnormalities, genetic influences, and the presence of anomalous centers of ossification may also contribute to the development of this condition. We present two patients whose clinical histories indicate a traumatic etiology of osteochondrosis dissecans of the glenoid. We also discuss the radiological, clinical, and etiological features of this entity. PMID- 2218588 TI - The sclerotic pedicle--how many causes are there? AB - The sclerotic pedicle is a commonly encountered roentgen sign that may be associated with numerous conditions, both benign and malignant. The following paper discusses the common as well as the unusual causes of this interesting phenomenon and demonstrates the radiographic presentations of the various etiologies. PMID- 2218590 TI - Limb shortening secondary to complications of vascular cannulae in the neonatal period. AB - Four cases of limb shortening presenting in childhood are described. All four children had been managed in a neonatal intensive care unit and had developed complications following the insertion of intravascular cannulae. In two, lower limb shortening and deformity were secondary to direct epiphyseal damage following extravasation of calcium or dextrose from a peripheral venous line. In the other two, forearm shortening followed ischaemia, secondary to either radial artery thrombosis from a radial artery cannula or spasm of the brachial artery following extravasation from a venous cannula in a neonate who also had a radial artery cannula. These cases highlight an important complication of the use of vascular cannulae in neonates and the problems this may pose to the orthopaedic surgeon. PMID- 2218592 TI - Enchondroma protuberans. Report of a case and its distinction from chondrosarcoma and osteochondroma adjacent to an enchondroma. AB - Enchondroma protuberans has been defined as an exophytic enchondroma of a long bone. We contrast a case of enchondroma protuberans with two cases of coincident enchondroma and osteochondroma. Our cases and the previously published ones lead us to believe that enchondroma protuberans is probably an enchondroma variant and that its unusual growth pattern may be related to the oblique orientation of the proximal humeral epiphysis. Unlike osteochondroma, which may be treated surgically by removing the cartilage cap and, in some cases, the stalk, enchondroma protuberans requires intralesional curettage. Enchondroma protuberans must be distinguished radiographically from chondrosarcoma. PMID- 2218591 TI - Role of routine percutaneous hip aspirations prior to prosthesis revision. AB - We undertook a retrospective review of 78 percutaneous hip aspirations performed as a prerequisite to prosthetic revision or replacement. Although the majority of the patients were already scheduled for revision or replacement, many aspirations were requested as part of the "routine" algorithm in the evaluation of a painful hip. Cultures from the aspirated fluid were compared with those obtained intraoperatively (where possible) and to the clinical suspicion of infection. Many of the selected patients had clinical and/or radiographic indications of pain. Our results yielded no evidence of infection (0%) when there was no clinical suspicion of infection (60 patients). Clinical suspicion for infection was high in 7 patients; aspirates demonstrated infection in 5 of them. One aspiration was false negative for infection, but subsequent intraoperative cultures were positive. When the clinical suspicion was intermediate or equivocal (11 patients), results were negative in 9 and positive in 2, both at aspiration and intraoperatively. We contend that routine percutaneous hip aspirations do not need to be performed when a prosthetic revision or replacement is contemplated if the clinical suspicion for infection is low. Hip aspiration and arthrography should not be eliminated, however, when the clinical suspicion is equivocal or high or when there is no apparent cause for a painful prosthesis. PMID- 2218593 TI - Radiographic and computed tomographic findings in hydatid disease of bone. AB - Twenty-six patients with hydatid disease of bone were evaluated by means of radiography and conventional tomography. Fourteen patients underwent high resolution computed tomography (CT). In two patients with vertebral disease, magnetic resonance imaging (MRI) examination was also performed. Seventeen patients underwent surgery with histological examination in all. Based on the surgical data and gross examination of the specimen, the radiographic and CT findings have been reviewed to identify the most characteristic radiographic features and to assess the role of CT. Radiographic finding of hydatidosis are rarely typical in bone, and only in a few patients can CT contribute to the diagnosis. On the other hand, the local extension of the lesion both in bone and in soft tissues, which is essential in planning surgery, is always demonstrated well by CT. PMID- 2218595 TI - The radiologic assessment of post-traumatic vertebral stability. PMID- 2218594 TI - Ultrasound in degenerative cystic meniscal disease of the knee. AB - Ultrasonography of the knee joint using small-parts probes was performed on 27 patients with clinical findings suggestive of meniscal cystic degeneration. Surgical or arthroscopic confirmation of sonographic findings was obtained in all cases. Sonography delineated the shape and structure of the meniscal profile and any degenerative changes. In the initial stage (6/27 patients, 22%), minor structural irregularities could be observed. Small, round, transonic cysts were found in 8 patients (30%); these lay mainly within the meniscus and were movable during stress flexion of the leg. In more advanced cases (8/27, 30%), larger cysts sometimes protruded on the skin surface. In 3 patients (12%), the soft tissue swelling was associated with a normal sonographic aspect of the menisci, but sonography could demonstrate an effusion of extra-articular origin. Ultrasound is a simple and effective method for the assessment of degenerative cysts of the menisci. It allows a reliable differential diagnosis between meniscal cysts and other causes of soft tissue swelling, and it is well suited for monitoring the course of the disease. PMID- 2218596 TI - Case report 610: Amyloid arthropathy of the left ankle. AB - In summary, a case of amyloid arthropathy of the left ankle in a 64-year-old patient with multiple myeloma is presented. The asymmetric presentation and site of deposition in the ankle were taken to be unusual. Involvement of both hips and the right shoulder was also suspected on subsequent evaluation. The patient's history and MR studies were essential in establishing the preoperative diagnosis. The extent of involvement, destruction of underlying cartilage, associated effusion and tenosynovitis were optimally defined by the MR images. The MR images also provided preoperative guidance in determining the approach and optimum site of biopsy. PMID- 2218597 TI - Case report 627: Septic arthritis of lumbar facet joint as initial manifestation of spondylodiscitis. AB - In summary, septic arthritis of a lumbar facet joint has been rarely discussed in the literature [1, 4]. In this case report the histological and bacteriological diagnosis was established by percutaneous needle biopsy guided by fluoroscopy and the response to treatment was confirmed by CT scans. PMID- 2218598 TI - Case report 628: Low-grade central osteosarcoma. AB - In summary, low-grade central osteosarcoma is a clinically recognizable rare subtype of osteosarcoma, representing 1.9% of all osteosarcomas found at the Mayo Clinic. The lesion is locally aggressive but also has the potential for metastasis, particularly after local recurrence. The tumor may be difficult to distinguish radiographically and histologically from benign conditions, particularly fibrous dysplasia. This difficulty has led to inadequate treatment. In most cases, a wide surgical margin achieved by either local resection or amputation should result in a cure. Because of the low metastatic potential of the initial lesion, there seems to be no need for adjuvant chemotherapy. PMID- 2218599 TI - Case report 629: Osseous hydatidosis. AB - In summary, hydatidosis is a common infection that infrequently involves the skeleton. When this happens the prognosis is uncertain because of the possible extension of the disease and serious complications, (e.g., pathological fractures, visceral involvement, neurologic damage from vertebral involvement). For this reason, simple curettage is not sufficient for cure and no medical treatment can surely eradicate the disease. Hydatidosis, in our opinion, should be staged and surgically treated like a malignant tumor (e.g., with wide surgical margins). Medical treatment is useful in association with surgery and remains the only therapy for inoperable lesions. A case of echinococcosis of the hip joint in a 37-year-old man has been reported. In this case the clinicoradiographical features suggested pigmented villonodular synovitis. Proof was obtained on the basis of a frozen section on biopsy. The clinical and laboratory characteristics of hydatidosis were discussed, with emphasis on the medical and surgical treatment of the disorder. PMID- 2218600 TI - Case report 631: Neo-osseous porosis (metaphyseal osteopenia) in polyglandular autoimmune (Schmidt) syndrome. AB - In summary, a case is reported of a patient with the radiographic findings of diffuse, symmetrical metaphyseal osteopenia of long bones. A constellation termed neo-osseous porosis, associated with polyendocrine failure (Schmidt syndrome) involving the thyroid gland, adrenal glands, and gonads has been described in this case. Neo-osseous porosis has been observed previously in idiopathic juvenile osteoporosis. This case represents the first instance in which this distinctive radiographic picture has been observed in the setting of specific (multiple) endocrine dysfunction disorders. PMID- 2218601 TI - Health inequities in Europe. PMID- 2218602 TI - Health inequities in Europe. Introduction. PMID- 2218603 TI - Health inequities in Europe. Comparative review of sources, methodology and knowledge. PMID- 2218604 TI - Health and social inequities in Belgium. AB - This paper presents two different yet complementary on-going studies related to the understanding of the mechanisms leading to social inequalities in health. The first part is devoted to a differential morbidity survey held in southern Belgium. It confirms that striking differences exist in the period around birth between social categories, and between the three districts under study. In a multivariate approach, differences remain between the social categories and between the district samples, which classically studied socio-demographical, behavioural and medical characteristics cannot fully explain. The role of cultural factors is analysed and discussed through the concept of 'health culture' and alternative hypotheses are reviewed in the light of the results. The second part reviews the studies conducted on the so-called avoidable mortality in the EEC and more specifically in Belgium. The concept of avoidable mortality is discussed, as well as its utility from the standpoint of the present concern on social inequalities. Differences between EEC countries are large, and even within Belgium there are important disparities between the districts. The role of health care supply has not been demonstrated yet in these two contexts. For Belgium, it appears that a major part of the unequally distributed mortality is constituted by causes of death considered as avoidable. Moreover, the most discriminating causes of death are overrepresented in socially deprived districts. The two perspectives are confronted in order to delineate perspectives for future research and operational outcomes for policy making and interventions. PMID- 2218605 TI - Health and social inequities in the Federal Republic of Germany. AB - The close relationship between social class and health status makes for the fact that indicators of health are supposed to tell something about the general conditions of life in the social structure of a particular country. This is one reason why trends in health and social inequities are to the foremost interest of the sociologist. Because the epidemiological literature in the Federal Republic does not allow one to consider trends over time, this paper tries to construct indicators from official statistics which have been regularly collected. The set of indicators discussed include data on mortality, age-at-death, morbidity as well as data related to health care and health risks. This discussion shows that, despite improving life expectancy and age-at-death figures, the major social class differential in health status has remained relatively stable over time, with a minor trend toward reduction in some figures. Since official statistics focus mainly on persons who are integrated in the labour market, only some groups with special risks may be detected. More information is certainly needed on disadvantaged groups with probably high health risks like the unemployed and those who subsist on welfare payments. PMID- 2218606 TI - Health and social inequities in Finland and elsewhere. AB - This review summarizes results of a number of studies on health and social inequities in Finland in comparison with other countries. Comparisons over time have been made when possible. Inequities in mortality in Finland can be compared with data from Denmark, Norway and Sweden as well as England and Wales plus Hungary. All countries show a similar relationship between mortality and level of education. No major changes in this relationship can be observed during the 1970s. Data on morbidity and perceived health complete the picture obtained on the basis of mortality data. Inequities concern various dimensions of health. Taken as a whole, the data suggest that the pattern of health inequities is more accentuated in Finland than in other Nordic countries. PMID- 2218607 TI - Social inequalities in self-reported morbidity: interpretation and comparison of data from Britain and France. AB - This paper considers the results from national surveys of self-reported morbidity in Britain and France and discusses the implications for our understanding of social class differences in the propensity to report illness. The methods adopted in these surveys in the two countries are so different that any comparison of the results must be limited. However, evidence on the trends over time in illness reporting in both countries reinforces the impression that the survey methodology has a significant impact on the results in terms of social class inequalities. The discussion also considers some other possible explanations for apparent changes in the propensity to report illness. It is concluded that in both countries the national survey data on class differences in self-reported morbidity has limitations and might be improved in the light of developments in survey methodology and the cross-fertilisation of ideas through international comparative studies of the subject. PMID- 2218608 TI - Interpreting inequalities in the Hungarian health system. AB - In reviewing the Hungarian situation it is said that the ideals of a higher living standard and economic security have a much broader appeal in public opinion than equality. The impacts of state intervention to reduce inequalities are reduced by several factors such as the tipping system and centralization. Official statistics do not entirely shed light on prevailing inequities in health, in particular those related to phenomena outside the health system, i.e. there is a heavy biomedical bias. Some contradictory developments are identified. One of these is that successful factories have created independent industrial health care services for their workers which not infrequently provide a higher quality of care than the state system. Furthermore, sociology has not played that generalizing and integrating function in the uncovering of inequalities in health as it has in Western countries. One of the rare sociological studies in the field shows that the population considers health only fourth among other desired values. Due to the increase in mortality, the issue of health has recently become more focused in the public debate. In general, this paper considers that the health system conforms with other Hungarian social realities in the realm of economics and politics as well as in value-orientation. This has been reflected in the recently reorganized ministry that now also comprises social welfare. PMID- 2218609 TI - Health and social inequities in Ireland. AB - This paper attempts to discuss the shape of inequalities in health in the Republic of Ireland by focusing on social class, gender and regional inequalities in health outcomes as shown in annual publications of vital statistics and in various research studies. The Republic of Ireland has a demographic profile of rapid population increase, unique in Europe. While the birth rate is the highest in Europe, the infant mortality rate is relatively low, yet the perinatal mortality rate is relatively high. Attempts are made to analyse social class variations in mortality and morbidity rates but, except for psychiatric care, Irish data on health by social class are scarce. There exist more data on gender inequalities which pinpoint the particular vulnerability of Irish women to ischaemic heart disease and certain types of cancer. Regional analysis of vital statistics reveals the vulnerability of people in urban areas (compared to rural areas) to cancer of the trachea, bronchus and lung, cirrhosis of the liver, tuberculosis of the respiratory system, pneumonia, and bronchitis, emphysema and asthma. In comparison to several European countries, Irish standardized mortality rates were the worst for urban women dying from lung cancer, and for urban men and women, Irish standardized mortality rates were the worst for non-rheumatic heart disease and respiratory tuberculosis. Various studies of morbidity of the elderly clearly reveal the hidden clinical iceberg of symptoms which are not presented to the health care system. Unfortunately, there is relatively little evidence of the health situation of disabled people, the travelling community or the long term unemployed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218610 TI - Health in Israel: patterns of equality and inequality. AB - While Israel does not have a nationalized health care system, 94.5% of its population is covered by comprehensive health insurance which includes curative and preventive ambulatory care as well as hospitalization. There is formal equality in access, distribution, and quality of the health services; nevertheless, there are pockets of deprivation that affect certain segments of the population. The paper focuses on three topics: (a) structure of the health care delivery system in terms of coverage, geographical and social distribution, and the public/private balance of the services; (b) processes of health care delivery in terms of utilization and quality; (c) health outcomes in terms of mortality, morbidity, health behavior, and disease vulnerability. Inequality in Israel appears to be structured in terms of six dimensions: coverage of health insurance, distribution of health services, the balance of public and private sectors of health services, utilization of existing services, quality of health services, and health outcomes as expressed by mortality, morbidity, health behavior and risk factors. Only two types of health care are not covered by the general health insurance: (a) dental care, and (b) long-term nursing care. Given the small area of Israel there are striking differences in the geographic distribution of health personnel of various types. There is evidence for gaps between needs and institutional services for many elderly who are on waiting lists for institutionalization. The ratio of primary care physicians to population is 1:2326 in development towns and 1:1852 in the older more established veteran communities. Kibbutzim, which are also located in large part in geographically remote areas, enjoy high quality health services and are not characterized by low ratios of health care personnel. In 1968-69, 6% of those insured by the sick funds purchased services at least once from a private physician, while in 1975-76 this figure rose to 32%. As in other countries, utilization of preventive services is generally correlated with socio-economic status and with education. While the network of primary care facilities in Israel is widespread and generally accessible, it is poorly integrated with the hospital system. Longevity has increased over the past years and is relatively high; 76.6 for women and 73.1 for men in 1984. Nevertheless, differences between Jews and non-Jews may still be seen among both men and women. The same may be said concerning mortality and especially with regard to infant mortality. Differences with regard to certain risk factors among Jewish infants and adults are correlated with socio-economic class and country of origin. PMID- 2218611 TI - Social differences in health and utilization of health services in Italy. AB - This paper describes the present pattern of mortality, morbidity, invalidity, use of services, and life-style according to relevant social characteristics. On the whole, the empirical evidence shows that lower socioeconomic groups, identified either by level of education, profession, or region of residence, continue to score worse on different health measures despite a general improvement in their state of health. Two results are of particular importance. Some southern regions accumulated a higher concentration of ill-health conditions and became multi problem areas. Middle and, above all, upper social groups have increasingly used the private health sector despite that fact that they are covered under the National Health Service provisions. This last development may be counter productive for the strategy of equalization introduced in 1978 with the NHS. PMID- 2218612 TI - Health and social inequities in Malta. AB - This paper focuses on the sources that are thought to lead to the genesis of health and social inequity in a small island community. It is largely a descriptive exposition, the main aim of which is to introduce the topic in Malta. Small size is the key geographical factor. This fact is dwelt upon to stress that although there are differences, say, between the two inhabitable islands, such differences are very small. Social homogeneity and an almost indiscernible urban rural difference are strong factors that reduce any tendency for regional inequities. Socio-cultural factors in Malta are largely determined by family life and its relation with the established church. The traditional Catholic way of life is depicted as gradually giving way to a more secular lifestyle. Politics is represented as the prime factor for causing division within the this society. This is not without reason since this factor has taken over the other cause of division, namely parochialism. Political factors determine the distribution of resources including health resources. The important economic factors are that there are no great differences between the high income and the low income groups. However, due importance must always be given to the subterranean economy. The health profile is that of a developed country with low infant mortality and a long life expectancy. Infectious diseases have been on the decline and their persistence is usually linked to areas that have remained underdeveloped. The disadvantaged groups identified are the chronically unemployed, single mothers, possibly a section of the migrant population and the elderly. PMID- 2218613 TI - Health and social inequities in The Netherlands. AB - Although there is some knowledge of inequity in mortality due to socioeconomic differences in the late nineteenth and early twentieth century, we know very little about present mortality differentiated by socioeconomic status. However, at present there are signs that interest in this theme may be increasing, particularly among government authorities. An overview will be presented of the few, rather scattered, existing data on regional and socioeconomic differences, mortality and other indicators of ill-health. This includes results of a secondary analysis of mortality differences among middle-aged Dutch men in a rural town. In this analysis the central question was whether mortality differences related to socioeconomic status could be explained by different risk factors. Socioeconomic status and risk factors turned out to be independent predictors of mortality. Finally, a short description will be given of the awakening interest for such data among health policymakers. PMID- 2218614 TI - Health inequalities in Poland. AB - This text is a second paper on relations between social inequalities and health in Poland. Our first paper was included in a collective report from a conference on social inequalities in health and health services utilization in 24 European countries (The Health Burden of Social Inequalities: Poland, pp. 157-170. WHO EURO, Copenhagen, 1986). It contains a description of social inequalities in health occurring in Poland, based on existing statistical data and information from scientific research. This text is an expansion of the previous one; here we present more updated information; we also try to identify some reasons for existing inequalities in health. PMID- 2218615 TI - Health and social inequities in Spain. AB - This article examines the relationship between health and social differences in Spain. The dominant explanatory models (medical, health system oriented and economical) have focused on health care as the main source of health. They have disregarded the role of socioeconomic variables in the genesis, development and cure of illness. In relation to the distribution of health, the variables analysed here are those of poverty, social class, sex, age, living conditions, lifestyles and some existential indicators using both official aggregated data and survey data. We conclude that Spain is a country with major economic, social and regional differences and manifests important variations in the health of its population. The evidence taken from the data presented here seems to indicate that poverty, living conditions and income play a relevant explanatory role. PMID- 2218616 TI - Health and social inequities in Sweden. AB - Sweden is one of Europe's most egalitarian countries. The social inequities in living conditions have been gradually reduced to a level that is more equal than in most countries in Europe. Even if general health development has been positive during recent years, data reviewed here indicate that there may be adverse effects for some groups which may increase inequities. This article presents results on inequities in health from the Public Health Report of Sweden 1987 and discusses causal mechanisms and implications for health policy. PMID- 2218617 TI - Health and social inequities in Switzerland. AB - Despite standards of living and life expectancy amongst the highest in Europe, Switzerland exhibits fairly substantial social inequities in health. As regards male mortality by socio-economic group, these differentials are both marked and independent of cause of death. There is a wealth of information on morbidity and disability supporting the hypothesis that people in lower socio-economic groups tend to age faster and suffer more at younger ages. It is similarly evident that infants of low class mothers, particularly those unwed, underprivileged immigrant, are at excess risk. The Swiss results are of political and scientific interest in that they suggest that the average wealth of a community does not determine health differentials. PMID- 2218618 TI - Health and social inequities in Turkey. AB - Social and economic policies of governments directly influence the health of the people. These policies, in turn, are determined by the national and foreign controllers of power. Economic and social factors in Turkey during the late 1970s led to a new modelling of the economic system, from a Keynesian to a market oriented and monetarist model. The state mechanism was also altered to form a centralized, authoritarian regime in order to enforce the requirements of the economy. As a result, the middle class diminished in size, inequalities in income distribution increased, unemployment climbed, the purchasing power of wage earners decreased, government spending for education and health was cut and new oppressive laws were enacted. Health services were already urban-biased and hospital-oriented, but new free-market measures were instituted which promoted private health institutions and attempted to transform state-owned and financed hospitals into self-supporting, independent business enterprises. The only school of public health was closed down; preventive medicine expenditures were lowered while hospital rates and drug prices were increased. All these changes affected the health status of the population. Mortality and morbidity inequalities had already existed between the rich and the poor, men and women, urban and rural settlements, educated and illiterate, West and East, always in favour of the former. However, the new policies exacerbated the inequities. Infectious diseases including tuberculosis increased, nutrition worsened, occupational diseases and work accidents rose to be the highest in Europe. The power-holding minority is not interested in the health of populations and is committed to pursue its social and economic policies. Ad hoc research, especially cross-sectional mortality studies repeated at regular intervals can provide data on the most vulnerable groups as no other valid information exists. There is little hope of these data being used for intervention unless democratic changes take place. PMID- 2218619 TI - The measurement of inequities in health: lessons from the British experience. AB - There has been an acrimonious debate about trends in inequality in health in the U.K. over the last couple of years. Whilst the acrimony is highly specific to the U.K. context, the terms of the debate contain general lessons for others who would venture into the same territory. This paper has focused on problems with using occupational classifications, with using groups of different size, with assessing trends in inequalities in death, with the measurement tool employed, with comparing patterns of ill-health and with the framework of explanation. The U.K. debate provides a good example of the first problem. Much of the debate has had to rely on the classification of occupation at the time of death by the Registrar General's Department. The scheme used was devised in 1911 and has persisted despite the massive changes in occupational structure since then. The groups now contain different occupational titles, and it is not at all clear what is being referred to by the RG scheme. Moreover, the balance of the RG groups has shifted dramatically. Any scheme applied regularly and routinely to mortality statistics over time will have these problems--it is not surprising that it is very difficult to interpret patterns of class death rates. The argument over trends in the U.K. has sometimes focused exclusively on the measurement tool--the standardized mortality ratios. Various alternatives have been proposed, in particular the Gini coefficient which clearly answers a different, possibly rather uninteresting, question. The correct way of comparing 'top' and 'bottom' is to devise a method which produces a group of constant size in the different communities or at different times. The focus on death rather than survivorship is queried as is the usual restriction to comparing rates of early death. Possibilities of comparing patterns of ill-health are examined in the fifth section. Whilst routine health care data or survey morbidity data are invaluable, it seems highly unlikely that they can be compared between communities or over time. The alternative is to develop a series of 'risk' indicators and these are discussed in Section 5.3. The examination of patterns of inequalities in death and ill-health highlights the complexity of discussing aetiology. We consider the balance between long-term and short-term effects and the possible role of (ill) health on the social mobility process, and problems of directly relating low income to poor health. PMID- 2218620 TI - Health and social inequities in Yugoslavia. AB - In Yugoslavia the problem of social inequities comes on the political agenda every time when society is in a crisis. This paper describes the pattern of social inequities in health. Data are mostly used from statistics. The features of health inequalities are shown. The marked inequalities exist regionally, among republics and provinces, in spite of the reallocation of resources. Health inequalities exist also among social classes however they are measured. Individually based measurement shows inequalities in health between all individuals of the population. As Yugoslav society is passing through severe economic crisis when social structure polarizes and becomes rigid--inequalities in health tend to increase. PMID- 2218621 TI - The economics of inequality in health: a bibliography. AB - Economists have until recently taken a back-seat in the debate on inequality and health, despite various suggestions that economic science has much to contribute to the clarification of issues surrounding that polemic. This article presents a bibliography of English-language sources which explicitly consider the economics of inequality in the health domain or present methods which might suitably inform the debate. Initially, an introductory guide to the literature is presented, followed by the bibliography itself. This second section is divided into four distinct parts in order to facilitate use: works of a general economic nature, including those on the measurement and extent of inequality; discussions of normative aspects of equity in health; positive analyses drawing on models of the demand for health and medical care; and a final sub-section that groups works from other disciplines which are indispensable background for future work by economists. PMID- 2218622 TI - Questioning the status quo: sickness absence research so far claims more than it should! AB - This article is in the nature of a cautionary tale for those working alongside any group of medics who are required to collect epidemiological data, or plan based upon data collected by medical experts without having access to that data. The field of work is occupational health and the specialised area is the relationship between socio-economic variables and absence from work due to sickness. The over-riding criticism of the sickness absence literature to date is that the use of analytical statistics is poor or in most cases almost non existent and that there is very little understanding of the epidemiological concepts of 'confounding' and 'effect modification'. An example is given of one particular statistical procedure, multi-variate hierarchical log-linear modelling, which if used by future researchers could prevent the recurrence of some of the previous problems. PMID- 2218623 TI - Levels of health development: a new tool for comparative research and policy formulation. AB - Levels of health development are formed by mathematically clustering countries using six health status indicators: crude birth, crude death, infant mortality and child death rates, and male and female life expectancy. Stratifying two international samples of 128 and 163 countries into levels of health development- groups with similar health status profiles--improves the results of regression analyses used to identify economic, political, social, educational, health and other health determinants. For this reason, health development levels are a systematic framework for delineation of health determinants. Earlier large scale statistical studies have been limited in their success in part because they did not partition their data sets prior to analysis, or used inappropriate criteria that blurred rather than heightened developmental differences in underlying social systems. These developmental differences regulate the way in which health status inputs are converted into health status outputs, defining the relative importance of health determinants at various developmental levels. At lowest health development levels (countries with poorer health status), the under development of economic, health and educational infrastructures creates a vacuum which allows international intervention (aid, investment, export/import activities) to play a dominant role in health status determination. At middle health development levels, health and educational infrastructures are better developed, but still secondary in importance as health status determinants to basic economic infrastructure. Demographic problems are particularly apparent at these levels. At higher health development levels, education, women's status, and political structure are especially important health status determinants. This research has facilitated the identification of health status determinants for use in health policy analysis. Recommendations for future research include use of findings in health policymaking by individual countries and by comparative researchers, and development of appropriate health systems models for each level of health development. PMID- 2218624 TI - Characteristics of women having abortion in China. AB - A pre-coded, closed response questionnaire was administered to women at abortion clinic sites in August 1985. The convenience sample was comprised of 1200 women, 200 samples in both Chengdu and the Lianshan Yi Autonomous Region in Sichuan Province, 400 in Nanjing and Jiangsu Province, and 400 in the municipality of Shanghai. The women were interviewed by physicians as part of the women's intake medical history. The sample yielded 574 respondents who were urban and 624 who were rural. The number of previous abortions reported ranged from 0 to 5. Nearly half of the abortion recipients had had at least one prior abortion and 18% had had two or more prior abortions. Education, age, marriage duration and residence have apparent effect on abortion order. The urban respondents reported an average of 1.08 children vs 1.60 children for the rural respondents. Approximately 72% of the respondents claimed to have been using a contraceptive method at the time they became pregnant. The most commonly used method was the IUD (41.6%), followed by the pill (21.3%) and the condom only (16.5%). Residence appeared to be the greatest factor determining the type of contraceptive methods. The data presented here are limited and cannot be generalized to the larger population. However, they do shed some light on the contraception characteristics of a group of women who undergo abortion procedures in China. Their response to questions to contracepting behavior prior to abortion suggests that the problem, in part, is behavioral. For example after the expulsion of the IUD, no other method was substituted to avert pregnancy. In order to alleviate the problem of contraceptive failure, and subsequent abortion, there are policy as well as training and education implications for the state. PMID- 2218625 TI - Reported versus recorded health service utilization in Grenada, West Indies. AB - Calls for household surveys to provide information on service utilization in less developed countries raise questions regarding the accuracy and reliability of reporting. This paper compares reported to recorded health service utilization for diarrhoea and any other morbidity over a 2-week and 3-month period for information obtained from a household survey in Grenada, West Indies. A sensitivity analysis is used to derive minimum and maximum estimates of the accuracy of reported utilization. Over-reporting utilization was found to be between 33 and 62% for diarrhoea and 49 and 81% for any other morbidity. Under reporting of all utilization was estimated to be between 47 and 65%. These results cast doubt on the utility of household surveys as a reliable source of information regarding service utilization. PMID- 2218626 TI - Length of unemployment and psychological distress: longitudinal and cross sectional data. AB - Data are presented from the second stage of a longitudinal study of unemployed young people, when their ages ranged from 19 to 24 yr. Data from the first stage, when their ages ranged from 16 to 20 yr, had provided support for a curvilinear hypothesis relating psychological distress or affective well-being, to unemployment duration. According to the curvilinear hypothesis, distress peaks at around 6 months and declines thereafter. In the present study three target groups were distinguished: those unemployed for 3 months or less, those unemployed from 4 to 8 months, and those unemployed for 9 months or more. On most of the dependent measures the 3 month, and 4-8 month groups did not differ, but the 9 month group was significantly worse off than either. It is concluded that the relations between length of unemployment and psychological distress, or well being, are different in teenagers and young adults. Possible explanations for the differences are discussed. PMID- 2218627 TI - Patterns of preference for information sources in the adoption of new drugs by specialists. AB - The present study investigated the adoption of new prescription drugs by specialists who treat serious disorders using relatively high risk drugs with potentially serious side effects. One-hundred and fifty-six specialists, primarily practicing in medical specialties, evaluated a number of drug information sources and reported their use of these sources both in their general drug adoption procedures and in the adoption of one of a number of target drugs. As predicted, the pattern of drug adoption among specialists is substantially different from that generally reported in earlier studies, which are usually based on samples of general practitioners or of general practitioners and specialists combined. Professional sources of information predominate throughout the process, both in adoption procedures generally used and in the adoption of target drugs. The majority of specialists reported contact with commercial sources at some stage in the adoption process for the target drugs, but these sources were not, as is often reported in the literature, the main sources of first news of a new drug, nor did they exert much influence at the prescribing stage. It is clear from these results that in future research on drug innovation, different classes of medical practitioners, such as specialists vs general practitioners, will need to be distinguished. PMID- 2218628 TI - The influence of social support on AIDS-related grief reaction among gay men. AB - This paper examines the relationships between instrumental and emotional social support and the experience of grief reaction in a sample of 180 gay men who had lost a lover or close friend to AIDS during the first 5 years of the epidemic. Structured, face-to-face interviews were conducted in mid-1985. Grief reaction was assessed through a newly developed 12-item scale (alpha = 0.85). Availability and adequacy of instrumental and emotional support were assessed with reference to the tasks of caretaking and emotional pain experienced during the lover's or close friend's illness with AIDS. The findings indicate that gay men who lost a lover or close friend to AIDS experienced symptoms of grief similar to those reported in studies of bereaved spouses and parents. The intensity of these grief reactions appears to be influenced by a number of factors. First, more intense grief reactions were observed among those who had taken care of their lover or close friend during his illness compared with those who did not act as caretakers. Second, while the simple availability of instrumental and emotional support was unrelated to grief reactions, the perceived adequacy of both types of support was strongly related to the level of grief. Respondents who had received inadequate help with caretaking responsibilities experienced more intense symptoms of grief subsequent to the death compared with those who reported receiving adequate caretaking support. Similarly, respondents who did not obtain adequate emotional support for the pain they experienced during the course of the illness reported more intense symptoms of grief compared with those who felt they had received adequate support.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218629 TI - Falls and subjective health rating among the elderly: evidence from two Israeli samples. AB - Prevention and treatment of falls in the elderly is one of the challenges facing practitioners today. Falls are known to be associated with health status and demographic variables, however relatively little is known about how falls affect the health perceptions of elderly persons. Data from two Israeli samples were analyzed to examine the relationship between reported falls and self-rated health. The first sample was collected in 1978 in home interviews from 96% of residents aged 65 and over of the town of Kiryat Ono (N = 1276). The second sample was collected from a national probability sample of 3494 urban Israelis in 1985, in home interviews. One-year incidence of falls was estimated from both samples at 23-24% for those over 65. Data from both samples showed that recent falls are negatively associated with subjective health rating. In Kiryat Ono, falls interacted with reported chronic conditions, so that the effect of a fall on subjective health status was only apparent in those with few chronic conditions. Among those who reported 4 or more chronic conditions, the occurrence of a fall had no independent effect on subjective health rating. In multivariate analyses of the national data, falls, and particularly those that happened in the home, or that required a visit to the emergency room had a negative effect on subjective health rating, after adjustment for age, sex, education, mobility and visual impairments and use of sleeping pills. PMID- 2218630 TI - An assessment of survey data on birthweight. AB - The objective of this analysis is to determine whether useful information on birthweight can be obtained from a retrospective survey. The 1986 Peru Demographic Health Survey collected both numerical weights (in grams) and subjective assessments of relative size at birth, for infants born during 1981 86. Simple tabulations suggest that reports of both measures are of reasonably high quality. However, a more detailed analysis demonstrates that exclusion of the large proportion (almost one-third) of missing responses on numerical weights can lead to biases in the resulting estimates of the incidence and correlates of low birthweight, of the level of infant mortality, and probably of the relative risk of mortality for low birthweight infants. The results emphasize the necessity of collecting data on the relative size of infants, in addition to information on numerical weights, in populations in which a substantial fraction of infants are born outside the formal health system. The subjective assessments allow the analyst to examine the extent to which infants with missing numerical weights are select and to assess the degree of bias in estimates which are based on the subsample of births with reported weights. PMID- 2218631 TI - Psychology, mental health care and the future: is appropriate transformation in post-apartheid South Africa possible? AB - In accepting the principles that psychology and politics are intertwined and that major political transformation in South Africa is inevitable, the question that arises is to what extent appropriate transformation of the mental health care system is possible in a post-Apartheid state. A variety of factors need to be considered in exploring this question: the affordability of extending the mental health service; the expense of tertiary care; the increased demand for treatment; Apartheid mental health professionals' resistance to change; the inclusion of non professionals within the care system, and community involvement; and the problems posed by having residential areas still occupied by certain racial groups in a post-Apartheid society. All these factors are likely to make the transformation of psychology and the mental health care system more difficult to achieve. PMID- 2218632 TI - Urbanisation and health: methodological difficulties in undertaking epidemiological research in developing countries. AB - Rapid urbanisation has historically resulted in complex societal changes which have had both beneficial and adverse effects on the health of communities. Recently, it has been recognised that the urban poor in developing countries are at greatest risk for several adverse health effects. The epidemiologist has a key role to play in planning to meet current and future health needs of urban communities. Epidemiological research needs to focus on understanding the relationship between the changes that occur with urbanisation and their impact on health, in order to identify those at greatest risk, to identify the important risk factors that are amenable to intervention, and to evaluate the effectiveness of interventions aimed at improving the health of urban communities. This paper addresses several methodological difficulties in conducting epidemiological research on urbanisation and health in developing countries, with particular reference to Southern Africa. These relate to the definition of urban areas and residence thereof, the comparability across areas of exposure and outcome information, the identification of intra-urban variability, selection bias in cross-sectional studies, associating outcomes with specific urban exposures in analytic studies, and determining appropriate interventions and means of evaluation. Ways of overcoming these difficulties are suggested. Epidemiologists need to address these issues in order to make a valuable contribution to the improvement of health in urban communities. PMID- 2218633 TI - The blood transfusion taboo of Jehovah's Witnesses: origin, development and function of a controversial doctrine. AB - Jehovah's Witnesses are not allowed to accept a blood transfusion. According to the Watch Tower Bible and Tract Society this therapy is a transgression of divine precepts. Additionally, in the judgement of the believers, secular proof is abundant these days; to them AIDS is a powerful justification to abstain from blood. Founded on the work of the anthropologist Mary Douglas, it is argued that the rejection of this medical therapy is based on perceptions of pollution and purity inherent in the Watch Tower Society's ideological concept of anti worldliness. Rooted in the movement's pre-war opposition to vaccination the implementation of the taboo was triggered by the prevailing social-political climate surrounding the Society during the Second World War, resulting in this intriguing and controversial religious proscription. For the community of Jehovah's Witnesses the blood transfusion taboo still functions as a significant mechanism of sectarian boundary maintenance. PMID- 2218634 TI - Psychological distress and mortality: evidence from the Alameda County Study. AB - The relationship between psychological distress, in this case depression, and subsequent risk of mortality is examined using data from the Alameda County (California) Study, an 18-yr, three-wave prospective investigation of psychosocial risk factors and health. The results indicate no relationship between psychological morbidity and all-cause mortality or specific causes of death. While these results are discordant with those reported from a majority of studies of psychiatric patients, they are concordant with a majority of community based studies of the general adult population. Possible methodologic explanations are discussed which might account for disparate results reported to date, in particular failure to control for the effects of co-morbidity of somatic disorders and socioeconomic status. PMID- 2218635 TI - Sociodemographic and health factors in the well-being of homeless men in Sydney, Australia. AB - Throughout the world, homelessness is generally increasing. This paper examines some of the historical precedents and, in an Australian sample, some of the factors leading to ill-health in this group. All studies have shown the ill effects on health of being homeless and in this group drinking alcohol and length of time on skidrow appear to be the major factors. It is also suggested that the homeless are generally from comparatively disadvantaged backgrounds before becoming homeless, and more likely to be migrants. They were also less likely to have ever married and more likely to have been in jail or psychiatric institutions. PMID- 2218636 TI - Modeling heart disease mortality with census tract rates and social class mixtures. AB - The relationship between social class and 1980 heart disease (HD) mortality in eight urban U.S. counties was examined by regressing age and sex adjusted census tract specific HD rates (N = 1211) on tract social class characteristics. The regression model indicated that lower middle class residents experienced a HD mortality rate 1.9 (95% CI = 1.3, 2.8) times the rate in the upper middle/middle class, while the working poor experienced a HD rate 4.4 (95% CI = 3.5, 5.7) times the rate in the referent class. Similar class effects were seen for both black and nonblack residents. The crude race effect (1.3 with 95% CI = 1.2, 1.4) was explainable by the concentration of blacks in the lower classes. The methods illustrate the ecologic regression of mixtures of mortality rates on mixtures of exposure in the presence of random tract effects which eliminates some of the problems associated with small denominators or zero rates in some tracts. PMID- 2218637 TI - Sport participation and perceived health status: a study of adolescents. AB - Although it is a well-accepted notion that sport participation enhances health, the precise nature of the relationship has been unclear. Based on a national survey of Icelandic adolescents, this study evaluates the direct and indirect effects of sport participation on perceived health status. It is shown that sport participation has a substantial direct effect on perceived health, controlling for other health related behaviours, psychological distress and disease status. Sport participation also affects perceived health indirectly through distress and smoking, but does not seem to operate through alcohol consumption. The meaning of these results and their implications for future research are discussed. PMID- 2218638 TI - Emergency department utilization by two subcultures in the same geographical region. AB - An exploratory study of emergency department (ED) utilization, comparing Israeli adult Jews and Bedouin Arabs was conducted. The data interpretation derived from the premise that health services utilization reflects not only morbidity patterns but characteristics of both subcultures and the structure of health services. The Bedouins in the study are a Moslem traditional society going through a rapid process of urbanization and modernization, with a relative deficiency in primary health services. Data were collected from the general ED admissions registry. Patients (17+) who arrived at the ED during the first week of every even month of one calendar year were selected for this study (6815 Jews and 583 Bedouins). The findings indicate that, in general Bedouins use the ED significantly less than Jews. They adjust to the structure of the ED services and use them, more than Jews, as a primary service. Yet, the hospitalization rates of the two populations are similar. In both subcultures the pattern of gender differences changes after the age of 45. The change, however, is in the opposite direction. Differences in ED usage among Bedouin age-sex groups are discussed in terms of changes in social status during a period of socio-cultural transition. PMID- 2218639 TI - Primary care practitioners' likelihood to engage in a bio-psychosocial approach: an additional perspective on the doctor-patient relationship. AB - On the basis of a comprehensive study among Israeli primary care practitioners a multivariate framework aimed at furthering the understanding of salaried physicians' likelihood to engage in a bio-psychosocial approach has been developed and empirically verified. The framework augments earlier work on physicians' behavior by further specifying the concept of bio-psychosocial approach and the incentives and preconditions for such an approach. Multivariate analysis highlights the weight of the motivating, facilitating and impeding factors in shaping the primary care practitioners' likelihood to engage in a bio psychosocial approach. Conclusions are drawn regarding implications for the organization of care providing organizations. PMID- 2218640 TI - The mortality of first and second generation Irish immigrants in the U.K. AB - The Irish have generally been ignored in studies of the health needs of ethnic groups in the U.K. despite being the largest immigrant group and having the highest Standardised Mortality Ratio of all first generation immigrants. Using the OPCS Longitudinal Study, the present paper shows that this excess mortality persists into the second generation Irish in the U.K., regardless of the part of Ireland from which their parents originated or whether one or both parents were Irish. The effects of social class, age, sex, year of entry to the U.K. and period of death are explored, and variations with these factors are found to be complex. PMID- 2218642 TI - Community pharmacy: a method of assessing quality of care. AB - Generalisability theory is presented as a research method for assessing the quality of health advice. The theory is applied to make a comprehensive assessment of primary health care advice given by community pharmacists. A random sample of pharmacies from all London postal districts were selected and visited for set periods throughout one year. During these visits all consultations on health or the use of drugs between pharmacists and clients were tape-recorded. Nine characteristics were derived by an external criterion panel on which the quality of advice in a random sample of consultations (50) was assessed using rating scales. Following the application of generalisability theory, operational conditions for the assessment were selected to obtain a generalisability coefficient of around 0.8. Nearly half the consultations achieved satisfactory scores on at least three-quarters of the criteria on which they were assessed. However almost a third were considered satisfactory on less than a quarter of the criteria, most of these being satisfactory on none of them. Performance regarding disease prevention/health promotion activity was poorest. Thus the quality of most consultations was found to be either very good or very poor, relatively few occupying the middle ground. PMID- 2218641 TI - Application of the verbal autopsy during a clinical trial. AB - During a community-based treatment trial of onchocerciasis with ivermectin, verbal autopsies were employed as one method to assess the safety of the drug. The verbal autopsy questionnaire was designed to determine causes of death and mortality differentials in the treated population. During the 8 months of surveillance here reported, 25 individuals died, yet only 9 of these deaths were certified. Seven of the deaths occurred to individuals who had been treated with ivermectin and the majority of the deaths occurred to children under 5, who were excluded from treatment. The verbal autopsy method was evaluated and validated by comparing the verbal autopsy diagnosis of cause of death to death certificate diagnosis, when available. In addition, verbal autopsies were retrospectively performed for all deaths which had occurred at the hospital during the 6 months preceding the start of the study, if these deaths were traceable to households in the surveillance population. We found that in 80% of the adult deaths, the verbal autopsy and death certificate diagnoses of underlying cause of death agreed. The verbal autopsy was less accurate in diagnosing child deaths which we attribute to the design of the verbal autopsy (being to detect potential drug related deaths in adults) and to the delay between death and interview. We conclude that verbal autopsies are an important addition to surveillance systems in remote areas where the absence or inadequacy of health information systems does not allow a thorough follow-up of all subjects in drug studies. PMID- 2218644 TI - Tolerance for ambiguity among medical students: implications for their selection, training and practice. AB - The practice of medicine has always been characterized by uncertainty. Yet, attempts to study tolerance for uncertainty in medicine have been few, and limited to its influence on specialty preferences and test-ordering behavior. In particular, studies have not investigated how the process of socialization into the medical profession affects tolerance for uncertainty. Based on the assumption that uncertainty and ambiguity are related concepts, a modified version of a tolerance for ambiguity scale was used to study Johns Hopkins medical students' (N = 386) tolerance for ambiguity (TFA) through 4 yr of medical school. In addition, using alcoholism as an example of a clinically ambiguous condition, the association between students' tolerance for ambiguity and their perceived role in diagnosing and treating alcoholism was also investigated. Results indicate that tolerance for ambiguity (1) does not change throughout medical school, (2) is lower among men, whites and students who are younger when they begin medical school, (3) is higher among prospective psychiatrists than surgeons, and (4) is lower among students who do not feel responsible for diagnosing and treating alcoholism. These findings suggest that tolerance for ambiguity may, indeed, affect practitioners' career choices and performance and that selection of medical students may be more important than medical training per se in influencing students' tolerance for ambiguity. If medical schools admitted students who possess a high tolerance for ambiguity, quality of care for ambiguous conditions might improve, imbalances in physician supply and practice patterns might be reduced, and the increasing ambiguity in medical practice might be better acknowledge and accepted. PMID- 2218643 TI - A pilot study for an HIV prevention programme among commercial sex workers in Bulawayo, Zimbabwe. AB - In a health education pilot study for a programme to reduce HIV transmission among commercial sex workers (CSWs), 113 CSWs were interviewed and observed in Bulawayo, Zimbabwe during 1989. The educational level of the sample was low and less than a quarter had another job, either as a self-employed vendor/hawker or a domestic servant. Inability to earn income in other ways was the major reason cited for engaging in commercial sex. Nearly half the sample went for check-ups every 3 months or more often. All interviewees had heard about AIDS, but they were uniformed about several facets of AIDS. CSWs reported that they worked an average of 3.6 nights a week, averaged 1.3 clients a night and charged a mean of U.S. $2.8 a session and U.S. $6.5 a night. CSWs reportedly saw a total of 221 clients in the past 7 days and used condoms with 87 (39.3%) clients. Nearly all CSWs said they had done something to reduce the risk of getting AIDS, but when asked what they had done, only 40% said they were using condoms more frequently and many cited ineffective precautions. CSWs who had a job, charged higher fees, experienced little client violence and believed that they were susceptible to AIDS were more likely to use condoms. Clients were a cross-section of Bulawayo society, with widely varying education, incomes and occupations and shared little except an interest in commercial sex. Ethnographic approaches demonstrated a lack of cohesion among CSWs and a consequent need to foster organized, motivated groups for health education, the importance of incorporating clients in health education and the feasibility of using bar security and sales personnel as health educators. It is concluded that health education is urgently needed among CSWs, but that it is equally important to direct health interventions at clients, many of whom are resistant to condom use. PMID- 2218645 TI - Belief in the efficacy of alternative medicine among general practitioners in The Netherlands. AB - A survey among 293 GPs in the Netherlands showed that many believe in the efficacy of common alternative procedures. High scores were especially found for manual therapy, yoga, acupuncture, hot bath therapy and homoeopathy. Other procedures, such as iridology, faith healing and many food supplements, were considered less useful. PMID- 2218646 TI - On lending a he'ping hand. PMID- 2218647 TI - On writing for reading. PMID- 2218648 TI - Assessing the risk of occupational acquisition of the human immunodeficiency virus: implications for hospital policy. AB - In determining infection control policy, it is essential to quantitatively assess the risk of transmission of human immunodeficiency virus (HIV) to health care workers and their families. The risk should be placed in perspective by comparing it with other occupational hazards. The risk of seroconversion from a needlestick injury can be calculated from the probability of a needlestick occurrence, the probability that the source patient is infected, and the probability of seroconversion, given an exposure. The risk of seroconversion due to drawing 1000 blood specimens from seropositive patients is between 86 and 470 in 100,000. The risk to surgeons from performing 25 operations on infected patients is approximately 272 in 100,000. The risk of fatal injury in the course of one year's work on a Louisiana oil rig is between 188 and 283 per 100,000. PMID- 2218649 TI - Anxiety levels and cancer fear in patients admitted for elective operations. AB - Patients who are to have elective operations project varying degrees of anxiety, and many spontaneously express fear (without basis) that their operation involves a diagnosis of malignancy. To measure total, covert, and overt anxiety objectively, we gave the Institute for Personality and Ability Testing anxiety test to 125 consecutive patients admitted for elective general surgical procedures. A simple survey of cancer fear was also completed. Chi-square and Fisher's exact test were used to compare categoric data, and linear regression and analysis of variance were used where appropriate. Total anxiety scores were in the upper quartile compared to the general population. Scores indicating fear of cancer were elevated in 75% of patients who had no history of or reason to suspect malignancy. Covert anxiety scores correlated with cancer fear scores, and both significantly decreased as age increased (P less than .05). Also, as age increased, the cancer fear scores decreased (P less than .002). Obese patients had higher scores of cancer fear than all other patients (P less than .0001). PMID- 2218650 TI - Synergistic effects of psyllium in the dietary treatment of hypercholesterolemia. AB - We investigated psyllium fiber supplementation as a means of enhancing the cholesterol-lowering effect of the phase I American Heart Association diet. Fifty nine subjects with total serum cholesterol (TC) levels ranging from 5.56 to 10.24 mmol/L (215 to 396 mg/dL) were given a 2-month dietary lead-in followed by 3 months of diet only (29 subjects) or diet supplemented with 20.4 g of psyllium daily (30 subjects). Unlike women, men had a significant decrease in levels of both TC (-8.0%) and low-density lipoprotein cholesterol (LDL-C) (-10.1%) during the dietary lead-in. Psyllium supplementation resulted in an additional 5.5% reduction in the TC levels as compared to diet alone. Psyllium supplementation combined with dietary lead-in resulted in an overall 17.3% decrease in the TC and a 20.0% decrease in LDL-C for men, with decreases of 7.7% and 11.6%, respectively, for women. Psyllium effectively enhances the cholesterol-lowering effect of the phase I diet. PMID- 2218651 TI - Surgical management of palmar hyperhidrosis. AB - Hyperhidrosis is an idiopathic pathologic condition characterized by excessive sweating beyond that required to cool the body. Disturbance of the central nervous system, endocrine system, or obesity has been associated with this condition. Patients have a history of several years of occupational or social embarrassment. Individuals of Japanese ancestry and Jews of Northern African, Yemeni, or Balkan descent are predisposed to the condition. Nonoperative therapy is merely temporizing and unacceptable because of lack of efficacy or side effects. Surgical intervention provides effective and permanent control. The key to surgical correction appears to be the division of the sympathetic chain above the T-2 ganglion and below the T-3 ganglion of the involved side with removal of the entire T2-3 segment with its corresponding spinal nerves. This paper presents our experience with the dorsal thoracic approach for interruption of sympathetic innervation for severe palmar hyperhidrosis. We also review surgical efficacy of various approaches to the sympathetic chain, as well as possible side effects of operative intervention. PMID- 2218652 TI - Nephrotoxicity associated with concomitant ACE inhibitor and NSAID therapy. AB - Angiotensin-I converting enzyme (ACE) inhibitors and nonsteroidal anti inflammatory drugs (NSAIDs) can be nephrotoxic and may synergistically compromise renal function. A computer-assisted study was done to asses the prevalence of compromised renal function and the clinical importance of this drug interaction. A search of the records of all patients seen in the University of Nebraska Medical Center Internal Medicine Clinic was conducted to identify cases involving renal insufficiency, therapy with ACE inhibitors, or therapy with NSAIDs. Records of cases meeting these criteria were reviewed for clinical correlation and revealed 2278 patients treated with NSAIDs, 328 with ACE inhibitors, and 162 with both. No nephrotoxicity was found in conjunction with monotherapy, but three cases of reversible renal failure were found in conjunction with combination therapy. Significant nephrotoxicity during the concomitant use of ACE inhibitors and NSAIDs is not uncommon, and attention should be drawn to this potentially important interaction. PMID- 2218653 TI - The absence of nephrotoxicity and differential nephrotoxicity between tobramycin and gentamicin. AB - We conducted a prospective, double-blind, randomized trial of gentamicin and tobramycin to evaluate differences in nephrotoxicity. We evaluated levels of creatinine, creatinine clearance, beta 2-microglobulin, and N-acetyl-beta-D glucosaminidase (NAG) as indicators of nephrotoxicity, and attempted to correlate them. Forty patients met the criteria for evaluation; 14 were given tobramycin and the remaining 26 received gentamicin. Significant nephrotoxicity, as defined by an increase in creatinine of 0.5 mg/dL, did not occur in either group. Increases in beta 2-microglobulin values were seen in 67% of the patients in the tobramycin group, and 52% of those in the gentamicin group. Elevations in NAG levels occurred in 54% of those in the tobramycin group and 52% of those in the gentamicin group. Elevation of NAG and beta 2-microglobulin levels was congruent in only 40% of the cases. We conclude that there was no significant difference in nephrotoxicity between gentamicin and tobramycin. Elevations of NAG and beta 2 microglobulin occurred at rates similar to those reported in the literature, but they did not correlate with significant nephrotoxicity. PMID- 2218654 TI - Comparative study of plasma epinephrine and norepinephrine concentrations during hemodialysis: measurement by high-performance liquid chromatography versus radioenzymatic assay. AB - We measured epinephrine and norepinephrine levels simultaneously using two methods of detection of catecholamines in plasma--radioenzymatic assay and high performance liquid chromatography with electrochemical detection. Measurements were made in 15 stable patients during hemodialysis. No statistical differences in intradialysis plasma concentrations were found for epinephrine or norepinephrine, and no statistical differences were found between the values of epinephrine and norepinephrine using the two different methods. No significant decrement in epinephrine or norepinephrine concentrations during the dialysis procedure was detected regardless of the method used. We conclude that the hemodialysis procedure does not affect the concentration of plasma catecholamines and that the two methods of detecting plasma catecholamines in patients with renal failure are equally accurate. PMID- 2218656 TI - Medicinal leeches: once again at the forefront of medicine. AB - Medical grade leeches have recently been used in the management of acute problems relative to venous congestion in patients with traumatic injuries and surgical problems. Specific cases, especially in the realm of reconstructive microsurgery, have demonstrated the effectiveness and application of leech therapy. Specific contraindications include arterial insufficiency from either anatomic or mechanical obstruction. We present five illustrative cases of successful therapeutic intervention. PMID- 2218655 TI - Acute promyelocytic leukemia: impact of hemorrhagic complications on response to induction chemotherapy and survival. AB - From 1976 to 1989, 21 adult patients with previously untreated acute promyelocytic leukemia were seen at the University of Virginia Hospital. We reviewed their cases retrospectively to determine the impact of hemorrhagic complications and other factors on treatment outcome. We observed a complete remission rate of 35%; the median survival in complete responders was 15 months. Evidence of disseminated intravascular coagulation was found in 13 (62%) of the 21 cases at diagnosis. Fatal intracranial hemorrhage was the leading cause of death, occurring in eight (40%) of the 20 patients evaluated. Initial leukocyte count greater than 4.0 x 10(9)/L and platelet count less than 20 x 10(9)/L were significantly associated with an increased risk of intracranial hemorrhage. In patients with disseminated intravascular coagulation, the rate of intracranial hemorrhage was reduced by treatment with heparin. The high mortality of 40% (8/20) due to intracranial hemorrhage during induction was a major contributor to the low complete remission rate of 35% (7/20) in this series of consecutive unselected patients with newly diagnosed acute promyelocytic leukemia. PMID- 2218658 TI - A modification of the supraclavicular approach to the central circulation. AB - Traditional anterior or posterior triangle approaches to the central circulation may be at times unsuccessful in the patient whose anatomy makes cannulation difficult. We used a supraclavicular approach to cannulation of the central circulation in 100 patients for intraoperative monitoring or insertion of renal dialysis catheters. We have had only two failures, both in patients for dialysis catheter placement, and no complications. Review of the literature reveals a similar history of success with variations of this approach. The supraclavicular approach is an easy cannulation technique for the inexperienced physician and a useful alternative to traditional approaches for the experienced physician. PMID- 2218657 TI - Comparison of cefuroxime axetil, cefaclor, and amoxicillin-clavulanate potassium suspensions in acute otitis media in infants and children. AB - In this randomized, blinded, multicenter comparison study, 377 infants and children with acute otitis media (AOM) received a 10-day course of an oral suspension of one of the following: cefuroxime axetil (CAE), 30 mg/kg/day; cefaclor (CEC), 40 mg/kg/day; or amoxicillin-clavulanate potassium (AMX-CL), 40 mg/kg/day. Clinical efficacy was determined by pneumatic otoscopy and tympanometric testing 3 to 5, 11 to 14, and 22 to 26 days after the initiation of therapy. There was a statistically significant difference among the three treatment groups with respect to clinical outcome; more patients in the CAE group (62%) than in the CEC group (46%) or the AMX-CL group (52%) had complete resolution of signs and symptoms of AOM (including effusion). Paired comparisons revealed a significant difference in efficacy between CAE and CEC and a nearly significant difference between AMX-CL and CEC. Taste acceptability was highest for CEC and lowest for this formulation of CAE. Significantly more patients in the AMX-CL group than in the CAE or CEC group had a side effect, primarily diarrhea, vomiting, or diaper rash. We conclude that CAE suspension has greater clinical efficacy than CEC and fewer side effects than AMX-CL. PMID- 2218659 TI - Dementia: what to do. AB - Dementia is a syndrome of acquired intellectual deterioration that interferes with personal or social functioning. Diagnosis requires historical information from the family and the mental status evaluation of orientation, recent memory, comprehension, calculation, and abstraction. Most dementias create permanent, even progressive cognitive deterioration, yet there are some presentations for which remission exists. Common reversible conditions include depression, drug toxicity, normal-pressure hydrocephalus, hypothyroidism, subdural hematoma, and neoplasm. Screening laboratory studies consist of urinalysis, chemistry profile, blood count, thyroid survey, vitamin B12 and folate measurements, serology, chest roentgenogram, computerized tomographic scan of the head, electroencephalogram, and electrocardiogram. Treatment focuses on potential reversibility, psychosocial issues, restoring deficits, and specific symptoms. PMID- 2218660 TI - Sarcoidosis ... or something like it. PMID- 2218661 TI - A personal history of the ectopic brain. PMID- 2218662 TI - The scope of scopes. PMID- 2218663 TI - Carl Moyer (1908-1970): surgical teacher of the mid-20th century. PMID- 2218664 TI - Duplex Doppler examination of a perinephric abscess in a renal transplant. AB - Perinephric abscess has no characteristic ultrasonic appearance or location. Differentiation from urinoma, lymphocele, or hematoma depends on clinical and laboratory findings. Therapy consists of percutaneous catheter drainage, surgical drainage, and antibiotic therapy. Acute rejection is the most common cause of decreased diastolic flow during the immediate postoperative period. Acute tubular necrosis does not usually alter blood flow unless it is severe. Duplex doppler ultrasonic assessment of the renal transplant during the immediate postoperative period may provide a valuable baseline for comparison if complications develop. Baseline and follow-up ultrasonography to evaluate diastolic flow can help determine whether a posttransplant patient should receive emergency or conservative therapy for complications. PMID- 2218665 TI - Simultaneous pneumococcal and Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome. PMID- 2218666 TI - Malignant melanoma and pigmented lesions: a diagnostic and management dilemma. AB - We document two cases of malignancy occurring at the site of partially removed benign nevi. Because of the difficulty in clinical diagnosis and the uncertainty in its behavior, we propose that any recurring melanocytic nevus expanding beyond the original surgical scar be re-excised and the specimen carefully analyzed to ensure complete removal. PMID- 2218667 TI - Intra-abdominal palpation of a nasogastric tube in the stomach does not assure appropriate placement. AB - Improperly placed nasogastric (NG) tubes have been associated with considerable morbidity. The only reliable indicator of correct NG tube placement appears to be the aspiration of gastric contents. We have reported a case of major morbidity from an improperly placed NG tube that perforated the cervical esophagus, dissected the mediastinum, and terminated in the omental bursa. No gastric aspirate was obtained by suctioning of the tube, but correct placement was presumed based upon the surgeon's direct intraoperative palpation of the tip of the tube. Failure to aspirate gastric contents should alert the practitioner to the possibility of improper NG tube placement. PMID- 2218669 TI - Hematoma of the optic nerve sheath after penetrating trauma. AB - We have presented a case involving the diagnosis and management of optic nerve sheath hematoma. Our patient's positive outcome demonstrates the usefulness of megadose steroid therapy for acute optic nerve injury. PMID- 2218668 TI - Disseminated strongyloidiasis in AIDS and non-AIDS immunocompromised hosts: diagnosis by sputum and bronchoalveolar lavage. AB - In conclusion, disseminated strongyloidiasis is a fatal disease that commonly affects the lungs. The disease should be suspected in an immunocompromised host who came from an area endemic for S stercoralis even years before the onset of symptoms or in patients with unexplained gram-negative bacteremia or meningitis. Treatment should be started promptly and should be maintained for a long time. PMID- 2218670 TI - Prevalence of HIV infection among intravenous drug users: a view from New Orleans. PMID- 2218671 TI - Thimerosal sensitivity. PMID- 2218672 TI - Allergic reaction to yellow dye no. 5. PMID- 2218673 TI - Lyme borreliosis and the heart. PMID- 2218674 TI - Fiberoptic bronchoscopy for investigating adenocarcinoma of unknown primary site. PMID- 2218675 TI - [Optimal management of the flux of patients during mass screening]. AB - The article entitled "The optimization of technological flows of patients at the department of automated mass medical check-ups of workers (DAMMCHW)" sets forth the issues related to the activities of the department providing computer-based dispensarization of workers at industrial enterprises. The specific character of medical check-up organization under the conditions of DAMMCHW is described. A functional scheme of technological flows of patients is provided. PMID- 2218676 TI - [The automated system of management of the urban emergency medical services]. AB - A description is given of the ways to improve the effectiveness of urban emergency medical care service without considerable increase of its material and manpower resources. These ways include the automation of the operative management process of the service and the use of optimum management procedures in the provision of emergency care. The main stages in the solution of this task are identified. PMID- 2218677 TI - [Rural medicine]. AB - There is a need for radical restructuring of training of physicians with subsequent post-graduate training every three years and quarterly improvement of self-education of physicians. Head physicians of regional rural hospitals should be released from all administrative and economic functions. This is the responsibility of an administrator with higher technical or economic education. Regional and rural Soviets should provide physicians-graduates with dwelling space or flats at their arrival to the place of work; ensure patronage for all kinds of care at rural regional hospitals, their departments and wards; undertake daily supervision and provision of rural hospitals with food products and in autumn time with firing. Rural physicians should be granted an opportunity each month to order food products for themselves and their families from collective farms at State and collective-farm prices. The Ministry of Health of the USSR should solve the questions of centralization of supply and standardization of equipment and medical appliances for rural hospitals. PMID- 2218678 TI - [Problem of the adequacy of therapeutic and diagnostic services for the population]. AB - The article defines the prevalence of paraclinical procedures and drug therapy among different groups of population. The data might be used for assessing the problems of health care delivery and also as a basis for dynamic evaluations in the light of multiaspect influence of medicine on the formation of population's health. PMID- 2218679 TI - [Various aspects of using the principles of insurance medicine in the USSR]. PMID- 2218680 TI - [General risk factors of chronic non-infectious diseases among schoolchildren in Kaunas and Moscow]. AB - Representative samples of 16-year-old school-children including 126 children from Kaunas and 124 children from Moscow were surveyed by one and the same team consisting of researchers from Kaunas and Moscow. The survey indicated a statistically valid higher level of systolic blood pressure among Kaunas schoolchildren as compared to Moscow schoolchildren of the same age group. Diastolic blood pressure was somewhat higher among Moscow schoolchildren. Moscow schoolchildren smoked statistically valid more often and more intensively. During leisure time boys from Kaunas and girls from Moscow were less physically active. A higher level of arterial blood pressure was found among schoolchildren with high rates of IMT and among non-smoking boys. There was no dependence between the duration of physical activity in leisure time and the level of arterial blood pressure. The established correlations between levels of general risk factors for chronic noninfectious diseases (CNID) among Kaunas and Moscow schoolchildren are important for the evaluation of the effectiveness of CNID integrated prevention programme. PMID- 2218681 TI - [Improving the organizational forms of early detection of arterial hypertension]. AB - Within scientific and practical integral programme of chronic noninfectious diseases prevention and control scientifically substantiated prevention procedures are being developed and introduced into applied public health with the object of reducing morbidity and mortality in the republic from leading non infectious diseases. Proceeding from the assumption that each fifth or sixth adult inhabitant of the republic has elevated arterial blood pressure and during recent years the indices of effectively controlled arterial hypertension are not improving, the search for new forms of arterial hypertension control is quite timely. The results of work of the prevention unit established at the regional department store suggests great opportunities for increasing the volume of screening for arterial hypertension, increasing population's awareness of the necessity of arterial hypertension correction. Enlisting medical students and sometimes senior pupils from secondary school to work in the prevention units established at non-medical institutions serves as an example of using additional resources for the control of arterial hypertension at the community level. PMID- 2218682 TI - [Ways of improving medical services for schoolchildren]. AB - The protection and promotion of schoolchildren's health might be ensured by means of differential approach to the use of different forms of organization of medical provision and its further improvement with due regard for regional conditions. The development of All-union programme "Schoolchildren" is needed which would provide for a scientific base for improving organizational and health-promoting activities at general education schools and boarding schools. PMID- 2218683 TI - [Improving health services for industrial workers]. AB - The purpose of the present sociohygienic study is to improve a system approach to the problem of workers' health protection at industrial enterprises. The methods of sociological investigations, organisational experiment, system analysis, modelling, and health statistics were used. The improved system of workers' health protection was developed, tested in the course of organizational experiment and implemented at the industrial enterprises which resulted in the reduction of temporary disability, occupational accidents and diseases. PMID- 2218684 TI - [Altruism, humanism and medicine]. PMID- 2218685 TI - [Traditional and folk medicine among the Ossetes]. PMID- 2218686 TI - [Anti-alcoholism activities of Bolshevik physicians (1904-1917)]. PMID- 2218687 TI - [New economic mechanism of public health administration: socio- economic aspects]. PMID- 2218688 TI - [Relations between district outpatient service and emergency care service in the treatment of elderly patients]. AB - On the basis of analysing the state of health care delivery for the elderly and aged population at prehospital stage (provided by emergency care service and district polyclinic) in big cities with a high level of aging of the population, a number of organizational activities for improving health care delivery for this group of population has been suggested. The data on peculiarities in the level, structure and nature of emergency care visits by elderly population are provided. The reasons for the irrational use of emergency care are discussed. The requirements of the populations under study for various kinds of specialized medical care are determined. Current tasks aimed at improving medical care for the elderly provided a foundation for the necessity to strengthen the succession and correlation between all links in the chain of prehospital care and to re calculate the workload in respect to applied public health institutions with due regard for age structure of the population in the region of health services. PMID- 2218689 TI - [Program-target method in hospital management]. AB - The experience gained in developing the system of targets for a number of urban multi-profile hospitals suggests an opportunity for using a programme-target method in the management of an inpatient facility. The Samashko All-Union Research Institute of Social Hygiene, Public Health Economics and Management has developed a system of programme-target management, consisting of relatively autonomous blocks: the identification of actually existing hospital problems; the elaboration of the conception of hospital development; the building of a tree of targets; the projecting of structures for hospital management; the elaboration and implementation of programmes. The identification of problems is based on the analysis of factographic tree of hospital targets. The analysis of the problem situation and possible ways of solving the problems allow to elaborate the conception of hospital development. In order to simplify the procedure for the building of a tree of targets the subdivision of targets into the targets results, targets-processes and targets-objects is being introduced. On the basis of tree of targets the structure of management is being projected and programmes are being developed. The uniformity of methods used in this system makes it possible to presuppose the possibility of applying them at any institution and at any level of public health management. PMID- 2218691 TI - [Population health surveys and their role in the development of public health programs]. PMID- 2218690 TI - [Improving coordination of scientific research on social hygiene and public health economics and management]. AB - The article describes the system of research coordination established in the country on the problem of social hygiene, public health economics and management. Shortcomings are analysed and ways are outlined of improving the carrying out of these functions by the head institute. PMID- 2218692 TI - [Expectant mothers from other cities hospitalized for delivery in Moscow]. AB - An analysis was made of geographical structure of women in childbirth from other towns who were admitted to maternity homes of Moscow during a year. Regions and districts were identified from which the flow of women was the greatest, a comparison was made with the number of deliveries in each region and also with educational level of women in these regions. PMID- 2218693 TI - [Computer technology and analysis of community health]. PMID- 2218694 TI - [Morbidity and physical development of children's homes residents]. AB - The data on morbidity and physical development of 647 children of preschool age from six children's homes of general type are provided. It was found that with age the number of children who come under I and II groups of health is decreasing and those who come under III and IV groups of health are increasing in number. The indices of physical development of these children are below the regional standards. On the average the physical development of these children is delayed approximately by one year. Health-promoting activities for children raised in children's preschool homes should include the follow-up by specialists, the optimization of general and motor regimen, proper nutrition. PMID- 2218695 TI - [Quantitative evaluation of the effects of environmental factors on health status indices]. AB - The article is devoted to the problem of improving the methods of data collection and processing in solving the question of evaluating the health effect of environmental factors. Circumstances are pointed out which hamper the acquisition of reliable and operative data. The ways of improving the effectiveness of computer use are considered. PMID- 2218696 TI - [Physical development and dental caries in schoolchildren]. AB - The study has been undertaken to examine physical development and stomatologic status of 1177 schoolchildren aged 7-14 involving 811 Russian and Nanai children. Proceeding from the obtained results the analysis of basic indicators of physical development and stomatologic diseases in children is presented. PMID- 2218697 TI - [Medical-genetic service and problems of prevention of hereditary diseases in the family]. AB - The article provides the scientific substantiation of the economic effectiveness of early identification and treatment of patients with hereditary diseases proceeding from the example of patients suffering from mucoviscidosis. It was found that the degree of cost-effectiveness is closely related to the organization of early identification and timely treatment of such patients. The authors prove that identification and treatment of patients with mucoviscidosis is cost-effective. PMID- 2218699 TI - [Control of the quality of therapeutic process in hospital departments]. AB - It is recommended to use the following indices for assessing the quality of hospital treatment: average hospital stay, the percent of repeated admissions with one and the same disease, the percent of discrepancy between clinical and postmortem diagnosis with subsequent expert evaluation of each case of death. The departments of surgery also find it necessary to take into account the frequency of postoperative complications, postoperative lethality and average hospital stay of operated patients. The well-founded complaints per 100 hospitalized patients can also be considered as indices. PMID- 2218698 TI - [Activities of women's consultation clinics in prevention of unplanned pregnancy]. AB - The data on women of reproductive age residing in the area serviced by an obstetrician-gynaecologist were provided; the proportion of women requiring the prevention of unintended pregnancy was determined, their socio-hygienic characteristics were established. The peculiarities in the activities of an obstetrician-gynaecologist in the field of preventing abortions and regulating women's reproductive functions were identified. On the basis of these data measures to improve the performance of women's consultation clinic in preventing the unintended pregnancy were determined. PMID- 2218700 TI - [Formation of healthy and practically healthy person groups in ambulatory care of the population]. AB - The out-patient department of an urban hospital conducted a comprehensive screening of all patients with acute diseases and all persons who applied for regular medical check-up. The continuity was established with other curative institutions and hospital departments. For convenience's sake all the patients were provided with "registration form". The positive effect of this work: the increase in the number of dispensary patients classified under I and II groups, identification of patients with early stages of different diseases. PMID- 2218701 TI - [Development of the concept of health and its promotion in programmed activities of WHO]. PMID- 2218702 TI - [The Pavlov session (on the 40th anniversary of a joint session of the USSR Academy of Sciences and the Academy of Medical Sciences dedicated to I. P. Pavlov's physiology teachings)]. PMID- 2218703 TI - [Traditional medicine of Vietnam: history and current trends]. PMID- 2218704 TI - [Structure of regional complex programs: "Health"]. AB - The development and realization of regional programme "Health" should be determined in accordance with problems in population's health and their hierarchy. This determines the formation of functional and target structures of the programme. The target structure of a regional programme includes programmes of different territorial level and nature aimed at health protection of different populations, prevention of diseases, realization of functions of the society and population at large. PMID- 2218706 TI - North American Spine Society fourth annual meeting. Quebec City, Quebec, Canada, June 29-July 2, 1989. Proceedings. PMID- 2218705 TI - Relationship between duration of spinal cord ischemia and postoperative neurologic deficits in animals. AB - Twenty hogs were administered the following procedures before, during, and after overdistraction of the spinal column at T5-T6: somatosensory (SEP) and neurogenic motor evoked potentials (NMEPs), hydrogen clearance procedures, Stagnara wake-up tests, and aortic-injection of silastic plastic. To ensure that overdistraction was possible, a nonosseous, circumferential osteotomy was made at T5-T6 and distraction applied in one-ratchet increments using Harrington instrumentation. Overdistraction was maintained for 3, 5, 6, 10, 15, 20, 25, or 30 minutes. Results indicated that the duration of overdistraction, as represented by lost NMEPs, was always correlated with the animal's clinical status on wake-up test. If overdistraction was maintained more than 6 minutes, 100% of the animals demonstrated positive wake-up results; if maintained between 5 and 6 minutes, 75% demonstrated positive wake-up results; and if maintained less than 5 minutes, only 25% demonstrated positive wake-up results. Time-to-loss of the NMEPs and SEPs, after onset of overdistraction, fell within two groups: slow and fast. In the slow group, it required slightly more than 20 minutes (mean = 20.6) for the potentials to be lost, while in the fast-loss group data were lost in slightly less than 4 minutes (mean = 3.6). Blood flow studies and inspection of the spinal cord revealed that the mechanism of action for the slow group appeared to be ischemia of the spinal cord that extended several centimeters above and below the site of maximum distraction. In the fast-loss group, it appeared that gross structural damage, with some very localized ischemia, were the mechanisms of actions influencing the integrity of the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218707 TI - Spinal sensory and motor tract activation after epidural electrical stimulation in the cat. AB - Somatosensory evoked potentials (SEPs) after peripheral nerve stimulation and motor evoked potentials (MEPs) after transcranial stimulation have been routinely used as monitors of the viability of pathways in the posterior and anterior spinal cord, respectively, in patients undergoing spinal cord surgery. To assess total spinal cord function, both of these procedures must be performed simultaneously, which is both cumbersome and technically difficult. The objectives of this study were to demonstrate both sensory and motor spinal tract activation after epidural electrical stimulation of the cat spinal cord. Thirty seven adult mongrel cats were anesthetized with ketamine, intubated, and maintained with Ethrane and nitrous oxide. Stimulating electrodes were placed over the right dorsolateral spinal cord epidurally at T7 after a laminectomy. Recording electrodes were placed over the right L3 spinal cord epidurally, on the right L7 dorsal and ventral nerve roots, on the right and left sciatic nerves in the popliteal fossa, and in the right gastrocnemius muscle. After epidural stimulation of the spinal cord at T11, distinct reproducible potentials were recorded at each site. Activity in the L7 dorsal root implicated activation of spinal sensory tracts. Activity in the L7 ventral root and in the gastrocnemius implicated activation of spinal motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218708 TI - Histopathologic correlation of magnetic resonance imaging signal patterns in a spinal cord injury model. AB - Magnetic resonance imaging (MRI) provides a noninvasive method of monitoring the pathologic response to spinal cord injury. Specific MR signal intensity patterns appear to correlate with degrees of improvement in the neurologic status in spinal cord injury patients. Histologic correlation of two types of MR signal intensity patterns are confirmed in the current study using a rat animal model. Adult male Sprague-Dawley rats underwent spinal cord trauma at the midthoracic level using a weight-dropping technique. After laminectomy, 5- and 10-gm brass weights were dropped from designated heights onto a 0.1-gm impounder placed on the exposed dura. Animals allowed to regain consciousness demonstrated variable recovery of hind limb paraplegia. Magnetic resonance images were obtained from 2 hours to 1 week after injury using a 2-tesla MRI/spectrometer. Sacrifice under anesthesia was performed by perfusive fixation; spinal columns were excised en bloc, embedded, sectioned, and observed with the compound light microscope. Magnetic resonance axial images obtained during the time sequence after injury demonstrate a distinct correlation between MR signal intensity patterns and the histologic appearance of the spinal cord. Magnetic resonance imaging delineates the pathologic processes resulting from acute spinal cord injury and can be used to differentiate the type of injury and prognosis. PMID- 2218709 TI - Sagittal plane analysis in idiopathic scoliosis patients treated with Cotrel Dubousset instrumentation. AB - One hundred sixty patients with idiopathic scoliosis treated with Cotrel Dubousset instrumentation (CDI) underwent preoperative and postoperative sagittal plane analysis of the thoracic spine, thoracolumbar junction, and lumbar spine. The data suggest that mild to moderate improvements in thoracic hypokyphosis are possible. When crossing the thoracolumbar junction, reversal of rod bend and reversal of hooks on the derotation rod appear to provide the most physiologic sagittal contour. Cotrel-Dubousset instrumentation to the mid and distal lumbar spine can preserve and, at times, enhance lumbar lordosis. PMID- 2218710 TI - Long scoliosis fusion to the sacrum in adults with nonparalytic scoliosis. An improved method. AB - The first 17 adults with nonparalytic scoliosis having long fusion to the sacrum treated with the Luque-Galveston technique were reviewed. There were 3 men and 14 women. Their average age at the time of surgery was 47 years and the mean follow up period was 42 months. There were no neurologic complications and no patient developed significant loss of lumbar lordosis. Fusion occurred in 88% of patients. Two patients developed pseudarthrosis, neither of whom had anterior fusion at the level of pseudarthrosis. The best results occurred in patients who had two-stage procedures, with initial anterior lumbar fusion to the sacrum without instrumentation followed by posterior segmental instrumentation with the Galveston technique of fixation to the pelvis. PMID- 2218711 TI - Orthotic stabilization of thoracolumbar injuries. A biomechanical analysis of the Jewett hyperextension orthosis. AB - Spinal orthoses have been traditionally used in the management of thoracolumbar injuries treated with or without surgical stabilization. However, the orthotic treatment modality in the management of spinal fractures remains subjective since few objective data are available on the effectiveness of orthoses in stabilizing injured segments. This study used a finite element model of the spine to evaluate the effectiveness of a hyperextension orthosis in controlling the progression of deformities at the injury site under gravitational and flexion loads. Two types of injuries were simulated: a single-level injury at T12-L1 and a two-level injury at T11-T12-L1 segments. An injury of increasing severity was simulated by progressively reducing the bending stiffness of the affected segments relative to the normal values in flexion-extension mode. The interaction of a three-point hyperextension orthosis with the spine was simulated using experimentally measured stiffness properties of the orthosis. The authors' results suggest that in single-level injuries that cause up to 50% loss of segmental stiffness, the orthosis can restore normal resistance to deformity at the injured segments, under gravitational as well as large flexion loads. In loss of stiffness between 50% and 85% of normal, such as severe two-column disruptions, the orthosis can restore resistance to deformity under restricted patient activity level in the brace (low-flexion moment). Beyond 85% loss of segmental stiffness, such as three column injuries, the orthosis alone appears to be ineffective in preventing progression of deformity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218712 TI - Herniated intervertebral discs associated with unstable spinal injuries. AB - To examine the occurrence of traumatic herniated intervertebral discs associated with unstable spinal injuries, the authors reviewed the records of all patients with spinal cord level unstable spine injuries managed at their institution over a 26-month period. Ninety-three patients were identified. All patients had roentgenographic and computed tomographic (CT) evaluation. Magnetic resonance imaging was performed in 48 patients, and revealed the presence of a herniated intervertebral disc in 16, with the highest incidence being in the cervical spine. In the patients who had only plain film and CT scans, no disc pathology was identified. Magnetic resonance imaging provides a noninvasive means of examining intervertebral disc damage in unstable spinal injuries that might otherwise be unidentified and result in spinal cord injury at the time of surgery. PMID- 2218713 TI - Evaluation of surgical treatment for burst fractures. AB - The authors instituted a prospective, randomized study of patients presenting with acute burst fractures of the thoracolumbar and lumbar spine. Patients were alternately treated by posterior distraction using pedicle instrumentation (AO fixateur interne) or anterior decompression and instrumentation (Kostuik Harrington device). Forty patients are presented with a mean follow-up of 20 months. Preoperatively, there was significant canal compromise in 39 patients. This measured 44.5% in those patients undergoing posterior surgery and 58% in those patients undergoing anterior surgery. Postoperatively, this was reduced to 16.5% and 4%, respectively. There is a statistically significant difference between these two groups (P less than 0.0001). The mean preoperative kyphotic deformity was 18.7 degrees in those patients treated by anterior surgery and 18.2 degrees in the group treated by posterior surgery. At last follow-up, the mean improvement in kyphotic deformity was 9.3 degrees in the anterior group and 11.3 degrees in the posterior group. There is no statistically significant difference between these two groups. There were two implant failures of the anterior Kostuik Harrington construct and two implant failures of the AO fixateur interne. Blood loss was significantly higher in the patients undergoing anterior surgery, but there were no complications from thoracotomy and anterior decompression of the dural sac. This study supports the hypothesis that posterior distraction instrumentation can effectively decompress the canal and correct kyphosis in patients sustaining burst-type injuries. Anterior surgery, however, results in a more complete and reliable decompression of the canal. PMID- 2218715 TI - High lumbar disc degeneration. Incidence and etiology. AB - Three hundred seventy-nine consecutive magnetic resonance images (MRIs) with dual echo images of the entire lumbar spine were reviewed by the authors. All 379 patients presented with back pain and/or leg pain; they were interviewed and examined. Pain drawings were completed by all. There were 42 patients (11.1%) with disc pathologies involving T12-L1, L1-2, and/or L2-3 levels. Six patients (1.6%) had isolated disc degeneration and/or herniations limited only to these high lumbar segments. The remaining 36 patients had degenerative changes of the higher discs with variable involvement of the lower lumbar discs. Out of 12 spondylolistheses of L5 on S1, 7 had high disc pathologies at one or more levels presenting as skipped lesions; more severe high disc lesions were noted in Grade II slips. Isolated high disc degeneration is often associated with pre-existing abnormalities such as end-plate defects, Scheuermann's disease, limbus vertebra, and so forth, and stressful cumulative work activities such as in construction workers, airplane mechanics, and so forth. High disc degeneration was noted above or below previous fractures. High disc involvement with diffuse changes in lower lumbar spine was more commonly found in ascending fashion in older age groups, and in patients who have had previous lower lumbar spine surgeries, prior fusions in particular. Our findings suggest that altered mechanics are associated with the high lumbar disc pathologies. PMID- 2218714 TI - High levels of inflammatory phospholipase A2 activity in lumbar disc herniations. AB - Inflammation of neural elements is frequently mentioned clinically in association with lumbar radiculopathy. Mechanical embarrassment of neural elements by definable structural abnormalities is inadequate as a sole explanation of nerve injury in this condition. The purpose of this study was to demonstrate whether an enzymatic marker for inflammation (phospholipase A2) could be identified in human disc samples removed at surgery for radiculopathy due to lumbar disc disease. Samples were assayed for phospholipase A2 activity. The level of activity in the disc samples was compared with values obtained from other human tissues using the same assay. Specific activity (percent hydrolysis radiolabelled substrate) ranged from 238 to 1,014.5 nmol/min/mg. Mean activity for the human disc material was 568.7 nmol/min/mg, compared with 0.006 nmol/min/mg for human PMN, and 12.1 nmol/min/mg for inflammatory human synovial effusion. The pH and cation-related activity were identical to those demonstrated for phospholipase A2 inflammatory conditions. Human lumbar disc phospholipase A2 activity is from 20- to 100,000 fold more active than any other phospholipase A2 that has been described. As the enzyme responsible for the liberation of arachidonic acid from cell membranes, phospholipase A2 is the rate-limiting step in the production of prostaglandins and leukotrienes. These data establish biochemical evidence of inflammation at the site of lumbar disc herniations. PMID- 2218716 TI - The natural history of lumbar intervertebral disc extrusions treated nonoperatively. AB - The purpose of this study was to evaluate the natural history of morphologic changes within the lumbar spine in patients who sustained lumbar disc extrusions. All patients in this study were treated nonoperatively for radicular pain and neurologic loss. The following questions were addressed: 1) Does perithecal or perineural fibrosis result when extrusions are not removed surgically, and 2) Do disc extrusions spontaneously resolve, and, if so, how rapidly? The study population consisted of 11 patients with extrusions and radiculopathy. All patients were successfully treated nonoperatively. All had a primary complaint of leg pain and all had positive straight leg raising reproducing their leg pain at less than or equal to 60 degrees. Additionally, 87% had muscle weakness on a neurologic basis in a root level distribution corresponding to the site of disc pathology. Computed tomographic (CT) examinations were obtained on all patients at the inception of treatment. These studies were compared with follow-up MRI studies. The initial CT scans were evaluated for the following criteria: disc size and position, thecal sac effacement, nerve root enlargement or displacement, and evidence of central or intervertebral canal stenosis. In addition to the pathomorphology evaluated on the CT scans, follow-up MRI studies also evaluated disc hydration at the herniated and contiguous levels, and the presence of perithecal or perineural fibrosis. The following grading system was used to evaluate change in fragment size on the follow-up studies: Grade 1-0 to 50% decrease in size; Grade 2-50 to 75% decrease in size; Grade 3-75 to 100% decrease in size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218717 TI - Metabolic bone disease in lumbar pseudarthrosis. AB - Pseudarthrosis occurs in many patients who undergo lumbar spine fusion and it has been suggested that abnormalities of bone metabolism contribute to it. The authors evaluated 47 patients with pseudarthrosis for metabolic bone disease. Symptomatic patients with pseudarthrosis underwent metabolic bone evaluation. Abnormal results of laboratory tests were found in 7 patients (14.9%): 3 low or borderline 1,25 dihydroxy vitamin D3, 2 elevated 24-hour urine calcium, and 2 low serum testosterone. None of these abnormalities correlated with other clinical findings. Bone density was low in 14 of 24 patients in whom it was measured. Low values did not correlate with smoking or abnormal laboratory values. Metabolic bone abnormalities do not appear to play a frequent or significant role in pseudarthrosis after attempted lumbar spine fusion. PMID- 2218719 TI - Selective enrichment for temperature-sensitive secretion mutants of mammalian cells using plant lectin, concanavalin A. AB - The use of conditional mutants as a genetic approach to study protein secretion in mammalian cells requires the isolation of a large number of mutants. Because a procedure for the direct selection of mutants with secretion defects is not available, their isolation depends upon the selective enrichment of mutant phenotypes in a cell population. We have devised an enrichment strategy in which rat hepatoma cells unable to replace surface membrane receptors of a plant lectin, concanavalin A, are resistant to the cytotoxic effects of this lectin when administered at a nonpermissive temperature. This treatment yields a population highly enriched in cells that demonstrate temperature-sensitive secretion. Therefore, this selection strategy has important application in isolating temperature-sensitive mutants for use in the study of the mammalian cell secretion pathway. PMID- 2218718 TI - A randomized double-blind prospective study of the efficacy of pulsed electromagnetic fields for interbody lumbar fusions. AB - A randomized double-blind prospective study of pulsed electromagnetic fields for lumbar interbody fusions was performed on 195 subjects. There were 98 subjects in the active group and 97 subjects in the placebo group. A brace containing equipment to induce an electromagnetic field was applied to patients undergoing interbody fusion in the active group, and a sham brace was used in the control group. In the active group there was a 92% success rate, while the control group had a 65% success rate (P greater than 0.005). The effectiveness of bone graft stimulation with the device is thus established. PMID- 2218720 TI - Energy dependence of DNA-mediated gene transfer and expression. AB - When cells are transfected with calcium phosphate-precipitated DNA, most of the DNA is internalized through active endocytosis but a small pool is postulated to be internalized by passive diffusion. The relative importance of these two DNA pools in gene transfer and expression has never been examined. We now show that mouse Ltk- fibroblasts internalize greater than 90% of radioactively labeled, calcium phosphate-precipitated DNA by a temperature- and energy-dependent process but a small pool of 2-3% of radioactively labeled DNA may be internalized even at 4 degrees C or under energy depletion conditions. The contribution of these two pools of DNA to gene expression was examined by transfecting Ltk- cells with DNA from a plasmid encoding marker for both transient expression (human growth hormone) and stable integration (neomycin resistance). When cells were depleted of ATP during transfection, transient expression of human growth hormone was reduced to only 2% of control values at day 4 posttransfection. Under the same condition, stable expression of neomycin resistance also was reduced to less than 1% of the control. Therefore, these data showed that only the pool of calcium phosphate-precipitated DNA internalized through an energy-dependent process is ultimately responsible for transient and stable expression of exogenous genes. PMID- 2218721 TI - Relative frequencies of homologous recombination between plasmids introduced into DNA repair-deficient and other mammalian somatic cell lines. AB - Twelve mammalian somatic cell lines, some of them DNA damage-sensitive mutants paired with their respective wild-type parental lines, were assayed for their ability to catalyze extrachromosomal, intermolecular homologous recombination between pSV2neo plasmid recombination substrates. All of the somatic cell lines analyzed are capable of catalyzing homologous recombination; however, there is a wide range of efficiencies with which they do so. Five human cell lines display a fourfold range of recombination frequencies, and six hamster cell lines vary almost 20-fold. Linearizing one of the recombination substrates stimulates recombination in all but one of the cell lines. Two of the three paired mutant cell lines display a threefold reduction in their ability to catalyze homologous recombination when compared to their respective parental cell lines, indicating that the mutations that render them sensitive to DNA damaging agents might also play a role in homologous recombination. PMID- 2218723 TI - A transcriptional terminator between enhancer and promoter does not affect remote transcriptional control. AB - Enhancers stimulate transcription of RNA polymerase II-transcribed genes in an orientation-independent manner and over long distances. This stimulation is known to be associated with an increased polymerase density over the linked gene. However, many aspects of the exact mechanism of remote gene control remain to be elucidated. Based on some reports on RNA polymerase I transcription, we wanted to test whether RNA polymerase II enters at the enhancer and from there proceeds towards the promoter while synthesizing unstable transcripts ("scanning/readthrough transcription" model). For this, we have inserted a complete terminator region from the mouse beta-globinmaj gene between the SV40 enhancer and the rabbit beta-globin promoter. In contrast to what the model predicts, insertion of the terminator had no affect on remote enhancer action. Furthermore, we have determined the RNA polymerase density over the spacer DNA between enhancer and promoter, and over the reporter gene, by means of the so called run-on transcription assay. We find very low transcription of the spacer, but high transcription of the globin reporter gene. Thus, our data are not consistent with a scanning/readthrough transcription mechanism where RNA polymerase II would move from the enhancer to the promoter while transcribing the intervening spacer DNA. These and other findings are compatible with a model where enhancer and promoter are brought into close proximity, perhaps with concomitant looping out of the intervening DNA. PMID- 2218722 TI - Polyacrylamide gel analysis of polypeptides in gene transfer cell lines. AB - Differential polypeptide expression in gene transfer cell lines of limited genetic complexity was analyzed as a gene mapping strategy. Subcellular fractionation preceding two-dimensional gel electrophoretic analysis simplified protein patterns and revealed subcellular location of differentially expressed polypeptides. As a model system, human MET oncogene polypeptide was identified in gene transfer lines by this approach. Genes encoding five putative human proteins were identified and provisionally assigned to chromosomal region 7q21-31 or to chromosome 1. PMID- 2218724 TI - Antisense RNA inhibition of HPRT synthesis. AB - The abundant production of antisense hypoxanthine phosphoribosyltransferase (HPRT) RNA in NIH-3T3, COS, or HeLa cells leads to an inhibition of HPRT synthesis. HPRT enzyme levels in cells transfected with mouse HPRT antisense RNA expression vectors are reduced to less than 1% of parental cell activity, resulting in resistance to 6-thioguanine (6TG). The expression of antisense HPRT RNA leads to a marked reduction in the steady-state levels of endogenous HPRT mRNA. Furthermore, we demonstrate that intron-specific antisense RNA, complementary to sequences adjacent to splice donor or acceptor sites of the first intron of the mouse HPRT gene, are effective in depressing endogenous HPRT levels. These studies suggest that antisense RNA can inhibit gene expression in the nucleus, possibly by perturbing nuclear RNA processing. PMID- 2218725 TI - Antisense RNA production in transgenic mice. AB - There are many reports of antisense inhibition of gene expression in cultured cells. We have generated four strains of transgenic mice expressing antisense hypoxanthine guanine phosphoribosyltransferase (HPRT) RNA in brain, or heart and liver, or all three organs. In the brain of one strain, the level of antisense RNA in the different brain regions roughly correlates with the degree of inhibition of the native HPRT mRNA in those same regions. Despite this decrease of up to 60% of endogenous HPRT mRNA, no reproducible reduction in HPRT activity has been observed. Possible reasons for the differences between the effectiveness of antisense inhibition in cultured cells and transgenic animals are discussed. PMID- 2218726 TI - Gene complementing xeroderma pigmentosum group A cells maps to distal human chromosome 9q. AB - Phenotypic complementation of xeroderma pigmentosum group A (XP-A) cells by microcell-mediated transfer of a single rearranged neo-tagged human chromosome from a human-mouse somatic cell hybrid designated K3SUB1A9-3 was reported previously. Extended growth of this human-mouse hybrid in culture led to deletion of the small arm of the human chromosome, with concomitant loss of complementing ability when introduced into XP-A cells by microcell-mediated chromosome transfer. Cytogenetic analysis of both hybrids suggests that the complementing locus is on chromosome 9q22.2-q34.3, and Southern blot analysis confirms the presence of distal chromosome 9q sequences. PMID- 2218727 TI - [The status of the respiratory organs in students in Sabac exposed to increased air pollution]. AB - The authors followed up the health of 322 elementary-school pupils at Sabac who were exposed to increased air pollution with chemical agents (ammonia, fluor hydrogen, chloracetic acid, sulfur dioxide, soot). The mean annual concentration of these gases were above or insignificantly under maximally permitted values. The results of the examination were as follows: recurrent cough in 12.4 per cent of cases and clinical signs of chronic or obstructive bronchitis in 8.4 per cent of children. Values of vital capacity were under normal in 27.6 per cent of cases and almost in the half of children vital capacity was at the lower normal limit. FEV1/FVC was under normal in 15 per cent of cases and at the lower normal limit in about 18.6 per cent of children. In spite of a great number of children with positive cutaneous tests to inhalation allergens with Prick's method IgE was within normal limits in these children. Thus, a significant noxious effect of allergic components on respiratory organs should be excluded. This was also confirmed by spirometric measurements of the two subsequent maximal expiriums when differences of +/- 3% were registered. However, in children with allergic bronchitis the value dispersion was by 2-3 times greater. Consequently, the authors concluded that damaged respiratory organs in children at Sabac appeared in a greater number of cases than in other places and that these damages were due to increased concentrations of different chemical air pollution agents. PMID- 2218728 TI - [Vascularization of the insular cortex and claustrum in human development]. AB - The blood vessels of the insular cortex and the claustrum were studied in 26 foetal brains of 16--25-week-old foetuses and one adult brain without noticeable pathological signs. The labelling of the vessels was wade according to Duvernoy et al. (1981). In 16-week-old foetuses arteries of types A6 as the A5 were found in the insular cortex as well as the veins of type V5. In 19-week-old foetuses the arteries of type A4 and the veins of type V4 appeared as only cortical vessels. In the following stages of the brain development the shorter and shorter arteries appeared so that in 24-week-old foetuses one could see all the types of arteries from A6 to A1. However, in the period from 19 to 25 weeks, no vein shorter than that of the type V4 was found in the insular cortex. In the adult brain it was possible to identify all the types of arteries and veins in the insular cortex, but distances between the individual vessels were larger in comparison with those in the insular cortex of the foetal brains. There claustrum was vascularized by the arterial branches from the insular arteries, whereas in the adult brain the claustrum received some of the branches from the striate arteries as well. This pattern of the vascular supply may indicate the common origin of the claustrum and the insular cortex. PMID- 2218729 TI - [Acute meningitis without cutaneous manifestations caused by varicella zoster virus--intrathecal synthesis of specific antibodies]. AB - The results of virusologic and cytobiochemical evaluation of CSF and serum samples of four patients with acute viral meningitis (AVM), most probably induced by varicella zoster virus (VZV), are reported. In no case VZV infection was not cutaneously manifested. Aetiologic diagnosis was established according to the presence of specific anti VZV AVM, in spite of their presence in the sera. On samples detected by indirect enzyme immunoassay (EIA). Four different antibody indexes were used to prove that the antibodies were intrathecally synthesized. Other viral antibodies (HSV, mumps) were not evident in the CSF samples of the patients with VZV avm, in spite of their presence in the sera. On the other hand, anti VZV antibodies could not be identified in the CSF samples of the controls (AVM of other aetiology, meningism) in spite of their presence in the sera. A possible aetiologic link between anti VZV antibodies presence in the CSF samples and some neurologic syndromes is discussed. PMID- 2218730 TI - [Epidemiologic status of syphilis and gonorrhea in the area of Belgrade]. AB - The authors present the epidemiological situation of venereal diseases (syphilis and gonorrhea) on the territory of Belgrade over the past twenty years with a detailed analysis of the past ten-year period. Constant decrease in morbidity rate was recorded in both diseases. The study showed that both diseases, expressed a high degree of parallelism in the dynamics of their appearance. Gonorrhoea was more frequent, with the rate of 1:4-41 in favour of gonorrhoea; the rate depended on the age. The incidence of gonorrhoea was 3.5 times higher in males than in females. However syphilis incidence was 2.5 times higher. The wafey endangered age groups for both diseases were 20-29 and 15-19 years for gonorrhoea, and 30-39 years for syphilis. In people working in catering services, tourism, public traffic, craftwork, as well as students and unemployed persons the highest frequency of these two diseases was observed. There was no seasonal difference in the incidence of syphilis, while gonorrhoea was frequent in the Summer months. There were differences in incidence (recent cases) and prevalence (number of recorded cases) of syphilis. Of the total number of annually recorded cases 30-60 per cent were recent cases. Repeated cases (especially of gonorrhoea) were frequent. The epidemiological research showed that approximately 37 per cent of primary source of infection were never recorded due to the lack of evidence and careless sexual contacts especially in the adolescent population. PMID- 2218732 TI - [Activity of delta-aminolevulinate dehydratase and glutathione levels in the erythrocytes of patients with endemic nephropathy and in healthymembers of their families]. AB - In a previous paper a markedly decreased activity of delta-aminolevulinate dehydratase (ALA-D) in patients with endemic nephropathy and in 24.6% of their healthy family members, was found. In this study the possible mechanisms of the decreased enzyme activity and the level of erythrocyte glutathione in patients and in healthy members from nephropathic families, were studied. We established decreased ALA-D activity in endemic nephropathy patients and in some healthy persons from their families. The normal concentration of erythrocyte glutathione was found in all groups. However, it was possible to reactivate the ALA-D enzyme in vitro by addition of exogenous glutathione. The obtained results suggested a normal synthesis of ALA-D apoenzyme and the existence of some factors whose effect upon enzyme activity was mediated through a binding to the reactive groups in the active centre of his enzyme or by oxidation of he reactive groups. Therefore, increased concentrations of sulfhydryl compounds, mostly of reduced glutathione are necessary for an optimal ALA-D activity. PMID- 2218731 TI - [Lipids and total bile acids in the blood of patients with inflammatory bowel diseases]. AB - We evaluated the total plasma bile acids, total lipids, total cholesterol, total triglicerides, LDL-cholesterol, HDL-cholesterol, phospholipids and lipoproteins (APOA-A and APO-B) in 25 patients with inflammatory bowel disease: 20 with ulcerative colitis (UC) and 5 with Crohn's disease. In comparison to 17 healthy volunteers, the total plasma bile acids were decreased in all patients. The serum level of total cholesterol, LDL-Ch, HDL-ch and APO-A was significantly lower in patients with Crohn's disease and ulcerative colitis (p less than 0.01) than in normal controls; total triglycerides and APO-B were decreased only in the group with Crohn's disease (p less than 0.05). Thus, decreased values of total plasma bile acids malabsorption, and they suggest a more important romalabsortion, and they suggest a more important role of the colon in the preservation of bile acids. PMID- 2218733 TI - [Cervical maturation using Prepidil gel in pregnancy termination in primigravidas]. AB - The study investigated the possibility of pharmacological servical ripening induced by Dinoprostone (Prepidil Gel--Upjohn Co) prior to therapeutic abortion in primigravida. The study concerned patients-volunteers choosen by random. 73 patients were divided into two groups with the same average age, term of gestation, cervix consistency and passage through the cervical canal before the application of gel. In the first group therapeutic abortion was carried out 6 hours after the application of gle into cervical canal, and in the second group- 4 hours after the gel application. Cervical maturation, testified by its consistency and spontaneous cervical ripening, was equal in both groups (average delta Hegar I was 7.32 and delta Hegar II--7.02), and it enabled medical procedure only with the local anaesthesia with 2% hylocein in 82% ob pregnant women. In a fifth of patients ob both groups it was necessary to do additional mechanical dilatation, which was easily performed due to the already soft cervix; these patients were also administered 1 ampulla ob Fortral I.V. In both groups during the action of Dinoprostone there were no significant changes either in blood pressure or in body temperature. More expressed uterine activity, followed by initial and incompleted abortions, were more frequent in patients of the first group (3529%) than in those from the second group (17.95%) in which only contractions occurred (33.33%). The rate of gastrointestinal side effects was 29.41% in the first group and 41.03% in the second group. There was no uterine complication during the activity of Dinoprostone as well as during and after medical procedure. PMID- 2218734 TI - [Occupational injuries of the eye caused by optical irradiation]. AB - On the basis of the increasing number of everyday exposures to numerous artificial sources of optical radiation (ultraviolet radiation, visible light, infrared radiation and laser), the probability of occupational and other ocular damages is increasing. The risk of vision damage due to sunlight radiation also exists during the staring at the sun with unprotected eyes especially in the time of eclipse, and the long stay in the bright light. In addition to ultraviolet radiation and short wavelengths of visible spectrum ("blue light") the photochemical (actinic) damage mechanism of the retina can occur. Numerous sources of ultraviolet radiation may cause acute photokerattoconjunctivitis; the long-term exposure to ultraviolet radiation possibly contributes to aging of the lens and to senile cataract, and also increases the risk of occurrence of conjunctival carcinoma and malignant melanoma of the eye. The infrared radiation of high intensity can produce corneal damage, probably cataract, and genuine thermal injury of the retina. Laser retinal injury, in its nature, is thermal, thermo-mechanical or with direct electric field effect. PMID- 2218736 TI - [Moschcowitz's disease--effect of therapeutic plasma exchange and splenectomy]. AB - Moszkowicz's disease (thrombotic thrombocytopenic purpura), TTP, is an uncommon haematologic, neurologic syndrome which, almost regularly, terminates fatally. The disorder has a turbulent and fulminant course and is of short duration. The presented patient was treated with a combined therapeutic modality of intensive plasma exchange and subsequent splenectomy. This is the first case of successful treatment of TTP in Yugoslavia. The previous therapeutic approaches with infusions of fresh frozen plasma produced only transient or dubious responses. Clinical remissions were rare. In this patient, however, the plasma exchange with volume adjustment with the fresh frozen plasma or albumin produced restitution of the thrombocyte count to normal values and disappearance of all neurological signs and complaints. At that point surgical splenectomy was carried out with the concomitant extirpation of an accessory spleen circumstantially detected on exploration. Pathohistology of both spleens revealed typical tissue changes (disseminated hyaline and thrombocyte thrombi of small blood vessels) characteristic of Moszkowicz's disease. Following an uneventful splenectomy and discontinuation of all medicamentouse therapy the normal thrombocyte count was maintained without no sign of recurrence of neurological symptoms or manifestations. PMID- 2218735 TI - [Adrenocortical "incidentalomas" as a diagnostic and therapeutic problem]. AB - P. Carpenter (1986) used the term "incidentalomas" in connection with all incidentally discovered adrenal masses. Previously these masses were frequent incidental discoveries at autopsies, but now, with the increasing use of abdominal computed tomography. In the last 10 years 5 patients with incidentally diseases, significant number of them have been detected. In the last 10 years 5 patients with incidentally discovered adrenal masses (4 males and 1 female, aged from 37 to 66 years) were examined and treated in our Department. Long-lasting arterial hypertension was found in all of them, and in one patient here was impaired glucose tolerance with further evolution of diabetes. A possible excessive secretion of glucocorticoids, mineralocorticoids, androgenes and catecholamines was excluded. However, markedly elevated urinary excretion of pregnanediol, proved in all patients, indicated to a possible preservation of the first reaction in the biosynthesis of cortisol, at least synthesis of pregnenolone from cholesterol. One patient, submitted to a regular functional and morphological evaluation of previously discovered 'incidentaloma', showed no sign of expansion or pathological hormonal activity. Four patients were operated because of the suspected expansion and malignant alteration of the adrenal nodus. The histological proof of adrenocortical adenoma or hyperplasia, composed of the 'fasciculata-like' cells, postoperatively maintained elevated values of steroid precursors in urine, and also a finding of adrenocortical noduses in remained adrenal noduses, confirmed the presumption that such masses could be the non essential finding in long-lasting arterial hypertension and degenerative changes during aging. PMID- 2218737 TI - [Biliary mucinous cystadenocarcinoma of the liver]. AB - Biliary mucinous cystadenocarcinoma is an extremely rare tumour. Less than 50 cases have been reported. It is usually a multilocular cystic tumour covered with mucous producing epithelium, with papillary excrescences containing mucinous mass arising from bile ducts. The size of the tumour varies from 3.5 to 25 cm in diameter. It is more frequent in women. The majority of patients belong to the middle age population. We present a 63-year-old man who had been suffering from an epigastric and right subcostal pain of unknown aetiology for over 35 years. During the last 10 years he suffered from multiple attacks of cholangitis with high temperature, rigor, chills, pain and obstructive jaundice. Five years ago he had the attack of pancreatitis with retroperitoneal fatty necrosis for which he was operated on in another institution and cholecystectomy and pancreatic necrectomy were carried out. The attacks of cholangitis continued they were more serious and more frequent until June 1987, when the "cyst" in the left lobe of the liver, dilated bile ducts and "polyps" in the common bile duct were diagnosed by ultrasonography. During the operation advanced biliary cirrhosis, portal hypertension, splenomegaly, very dilated common bile duct full of jelly and the "cyst" in the liver filled with jelly, were found. The removal of the jelly and choledochojejunostomy resulted in temporary relief. Two months later he was reoperated for recurrent obstructive jaundice during which left lobectomy, partial excision of the cyst and cystojejunostomy between the rest of the cyst and another Roux-en-Y jejunal limb, were carried out.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218738 TI - [Stability of complete dentures. 1]. AB - The Author considers the necessary requisites for the complete denture's stability during masticatory function. This is due to the following anatomic and functional factors: a) Support tissues' morphology. b) Morpho-functional characteristics of the prosthetic tooth: unitary nupolivalent function in the different occlusal sectors. c) Linear arrangement of the teeth with unitary function along the "structural sagittal axis" or "central axis of dinamic and muscolar stabilization" of the mandible. d) Teeth's arrangement in the neutral or muscolar equilibration zone. e) Interalveolar axis' verticality of the teeth with unitary grinding function. PMID- 2218739 TI - [Stability of complete dentures. 2]. AB - There is a necessary correlation between the Monson's curve, due to the mandibular kinematics, and the interalveolar axis' inclination in the different occlusal areas with unitary function. In the triturating area the verticality of the interalveolar axis is necessary for the stability of the cusp-fossa relationship in centric occlusion and for the stability of the prothesis during mastication. The Author shows the occlusal morphology and the arrangement of the prosthetic teeth in the different skeletal classes in relation to functional interalveolar strength's direction. PMID- 2218740 TI - [Stability of complete dentures. 3]. AB - The author analyzes the fundamental parameters of the complete denture; stability occlusal in the eccentric mandibular movements. They are: a) Correlation between condylar and incisal guide and occlusal morphology of the dental-arches. b) Presence of interincisive and intercanine functional free space. PMID- 2218741 TI - [Epidemiological survey of the prevalence of dental caries in young thalassemia major patients]. AB - 47 patients with thalassemia major treated with blood transfusions were studied by the authors. The aim was to carry out an investigation on caries incidence. From the data collected in this investigation it was found that 90% of males and 66% of females showed caries, then there was a difference in percentage of caries between males and females. On the other hand the dmf and the DMF index showed quite the same values in males and in females. PMID- 2218742 TI - [Autoimmune pathogenesis of recurrent oral ulcers. 1]. PMID- 2218743 TI - [Tenoxicam in treatment of oral inflammation and pain]. AB - The efficacy of a new nonsteroidal anti-inflammatory agent, Tenoxicam, was valued in a study of 58 patients distinguished into 3 groups, group A consist of 29 patients with inflammatory diseases of the mouth, group 1B and 2B (29 patients) with acute postoperative pain. Drug was given at doses of: 1) 20 mg/die in group A; 2) 40 mg/die for the first two days and 20 mg/die for successive days in group 1B; 3) 20 mg/die in group 2B, for a period variable from 5 to 7 days. The outcomes showed that the administration of Tenoxicam resulted in a effective reduction of all inflammatory valued parameters (fever in 100%, inflammatory pain in 94% and edema in 90% of all cases) for the group A: acute postoperative pain was significantly reduced in group 1B where the patients have assumed drug at dose of 40 mg/die for the first two days and 20 mg/die for successive days. In group 2B (20 mg/die) drug's smaller dose showed reduced efficacy for control of postoperative pain. Although Tenoxicam was well tolerated and mild side effects were recorded only in 5% of cases. PMID- 2218744 TI - [Effect on periodontal tissue of a "cushioned" bristle brush. (S.E.M. analysis)]. AB - The Authors have made in vivo verification by means of replica technique observed with SEM any possible traumatic effects and gingival modification which a bristle toothbrush (Sanogyl, Berna) has on the soft tissues. The toothbrush has particular features which make it possible to perform an almost perfect dental hygiene of the papillar area, it does not produce any secondary negative effects on the gingival soft tissues. PMID- 2218745 TI - [Strategy in radiologic diagnosis: CT of the neck]. PMID- 2218746 TI - [Diagnosis of focal nodular hyperplasia]. PMID- 2218747 TI - [Hepatic hemangioma: an improved diagnosis using rapid, dynamic sequential computed tomography]. PMID- 2218748 TI - [Computed tomography of the skeletal system]. PMID- 2218749 TI - [Computed tomography of the pelvis]. PMID- 2218750 TI - Kimura's disease--a benign condition that may be confused with malignancy. A case report. AB - A case of Kimura's disease is reported. The importance of this rare benign condition lies in the fact that it is clinically similar to malignant disease. The important principle of confirming the diagnosis by histological examination before embarking on major surgery is highlighted. Similarity to and differentiation from angiolymphoid hyperplasia with eosinophilia is discussed. The patient underwent resection with functional clearance of the neck nodes, and is free from disease after a 2-year follow-up period. Improper management of this rare head and neck lesion may lead to unnecessary cosmetic deformity and significant loss of function. PMID- 2218751 TI - Acute airway obstruction in children with benign head and neck tumours. Case reports. AB - Infants presenting with acute airway obstruction secondary to cystic hygroma and neurofibroma are presented. Early surgical correction of large benign tumours of the head and neck is recommended to prevent life-threatening complications. PMID- 2218752 TI - Parotid haemangioma. A case report. AB - The presentation of a rare cavernous haemangioma of the parotid in a 17-year-old male is the twenty-first case in the English literature, and the first report in a black adult patient. The aetiology of this lesion is unknown and differs from that of the infantile capillary type. The pathognomonic signs of fluctuating size, discoloration and bruit are rare; the diagnostic hallmark in this case was spontaneous tumour regression. Doppler studies and arteriography may be valuable in diagnosis and management, in which surgical excision is the treatment of choice. PMID- 2218753 TI - Sarcoidosis with nasal obstruction and deformity. A case report. AB - Sarcoidosis is a relatively uncommon disease, seldom seen by ear, nose and throat departments. There are interesting head and neck and, more specifically, nasal manifestations. A patient with sarcoidosis presented at our department with nasal obstruction and deformity. Although these were the predominant features of the disease, the diagnosis was made together with other systemic signs. A case of sarcoidosis involving the nose is presented, with discussion emphasising the features more commonly seen by the ear, nose and throat surgeon. PMID- 2218754 TI - Ventriculosaccular carcinoma of the larynx. AB - The question of whether or not carcinoma arises in the ventricles and saccules of the larynx is a controversial one. These areas of the larynx have pseudostratified columnar ciliated epithelium. In the past several authors have not believed that carcinomas arise in these areas because of the absence of squamous metaplasia in their observations. However, other workers have been convinced that such tumours do arise and that they behave in certain specific ways. In order to clear up the controversy, these areas were studied in 154 laryngeal specimens examined by a serial sectioning technique. In this study 14.3% of the laryngeal specimens studied showed clear evidence of tumour emanating from these areas. Areas of squamous metaplasia with carcinoma in situ and frank invasion have been observed in many of these cases. These tumours spread by concentric enlargement within the paraglottic space and are often diagnosed late since they are difficult to observe from above. Patients who present with hoarseness and a mucosa-covered swelling in the false cord area should be carefully examined if a carcinoma arising in this area is not to be missed. PMID- 2218755 TI - Neonatal stridor. Five-year experience at King Edward VIII Hospital, Durban. AB - During the period January 1984-January 1989, 110 neonates were referred to the ENT clinic at King Edward VIII Hospital, Durban, with symptoms of upper airway obstruction. The medical records of these patients were reviewed in order to document the clinical presentation, diagnostic evaluation, pathological findings and therapeutic approach. All patients underwent a thorough clinical examination, postero-anterior and lateral chest radiography, soft-tissue lateral radiography of the neck and endoscopic evaluation. We outline our findings and briefly describe management. Of interest is the high incidence of vallecular cysts in this series (15%) compared with others. PMID- 2218756 TI - Nasopharyngeal carcinoma. An analysis of 100 Chinese patients. AB - Clinical manifestations in the first 100 patients with nasopharyngeal carcinoma to attend the ENT outpatient clinic at the Prince of Wales Hospital, Hong Kong, commencing in February 1986, are presented. All tumours were non-keratinising or anaplastic carcinomas, World Health Organisation types 2 and 3. Cervical lymphadenopathy was the commonest presenting complaint (43%), followed by nasal symptoms (32%) and aural symptoms (18%). On clinical examination 73% had cervical lymph node metastases, and 72% of patients were in stages III-V at presentation. Trivialisation of the symptoms by the patient and delay by the referring physician contributed to lateness of diagnosis. PMID- 2218757 TI - Hurthle cell medullary carcinomas of the thyroid gland. AB - Two medullary carcinomas of the thyroid (MCTs) composed entirely of Hurthle (oncocytic or oxyphilic) cells and containing follicular structures are described. Immunocytochemical analysis showed these tumours to be calcitonin-, carcino-embryonic antigen- and neuron-specific enolase-positive. The essence of this communication is twofold. Firstly, it highlights and draws attention to this unusual variant of MCT, which may be encountered at frozen section and misdiagnosed as a Hurthle cell tumour of follicular cell origin. Secondly, it undertakes a concise overview of the immunocytochemistry of Hurthle cell thyroid neoplasms and MCT. PMID- 2218758 TI - Are carotid body tumours malignant? AB - Carotid body tumours (CBTs) are slow-growing, malignant neoplasms by virtue of their local spread by continuity and contiguity and metastatic spread by lymph and blood. This article reports the findings of a pathological study of the growth characteristics of CBTs. PMID- 2218759 TI - The neglected disease of modern society and the Child Accident Prevention Foundation of Southern Africa. PMID- 2218760 TI - What are the prospects for improved health and increased longevity? PMID- 2218761 TI - Five years' experience of injured children. AB - This study was undertaken to analyse admission data on all patients seen in the Red Cross War Memorial Children's Hospital Trauma Unit during the period 24 April 1984 - 31 March 1989. Data were retrieved from computerised records completed on admission and were reviewed descriptively. Variations in age, sex and population group pattern for different causes of injury were evaluated together with data on the nature and place of injury and time seen. Data for analysis of nature of injury by cause were also retrieved, but over a 2-year period only (1986-1987). Accuracy of recorded data was assessed from a random sample of hospital records. During the 5-year period 57,468 patients were seen in the Trauma Unit, of whom 17.1% were admitted. In addition 6,377 cases of poisoning and 119 of near drowning were seen by the medical departments. Forty-three per cent of injuries were due to falls, which were the most important cause of injury in both admitted and non-admitted patients of all age, sex and population groups. Other main cause groups were bumps and blows (15%), transport (11%) and burns (11%). Transport and burn injuries had the highest admission rates. This is the first study of children's injuries in southern Africa and provides information essential to future design of paediatric trauma care systems and accident prevention programmes. PMID- 2218762 TI - Trends in childhood injury mortality in three South African population groups, 1968-1985. AB - Trends in major causes of injury mortality and the proportion of total deaths attributable to injuries from 1968 to 1985 for white, coloured and Asian children less than 15 years in the RSA were examined. There were 937 injury deaths in 1968 and 853 in 1985 but no clear trends in overall mortality rates were observed. There were, however, marked fluctuations in injury mortality rates from year to year with peaks in 1975 and 1981/1982. The impact of injury as a cause of death has increased relative to a decrease in other diseases, notably gastro-enteritis and malnutrition in children less than 5 years. Patterns varied considerably between age, sex and population groups. Overall, road and burn death rates decreased while drowning and assault rates increased. Reasons for observed trends are discussed and the need for the collection of reliable national data for the total population is highlighted. PMID- 2218763 TI - Injury-related mortality in South African children, 1981-1985. AB - Data on all registered deaths in children less than 15 years in the RSA (excluding Transkei, Bophuthatswana, Venda and Ciskei) were analysed for 1981 1985. Variations in age, sex and population group pattern for different causes of injury were evaluated. Injury accounted for 8% of deaths in children less than 15 years and was the leading cause of death between the ages of 5 years and 14 years (accounting for 43% of deaths). Motor vehicle accidents were the most important cause of injury deaths in all age groups except less than 1 year, when accidental choking and suffocation resulted in more deaths. Drowning accounted for 19% of injury deaths and burns for 11%. In 14% of injury deaths it was not determined if the injury was accidental or purposefully inflicted. In all age and population groups deaths among boys outnumbered girls. The impact and pattern of injury varied considerably between age and population groups and reasons for these findings are discussed. PMID- 2218764 TI - Patterns of referral to Red Cross War Memorial Children's Hospital, Cape Town. AB - Patterns of referral to Red Cross War Memorial Children's Hospital were studied to assess the appropriateness of referrals. From 1 July to 31 December 1987 all 9,288 referral letters presented to the hospital were collected and a sample (4,662 letters) analysed. It emerged that the patients were similar to those attending the outpatient department without referral, except that relatively fewer referred patients were black. The private sector, i.e. general practitioners, was the largest referral agency, followed by day hospitals. Most patients were referred to the outpatient department without an appointment. Of the specialist clinics, the surgical clinics (i.e. ophthalmology and ear, nose and throat) had the highest number of referrals. The majority of patients (84.9%) were not admitted. Only in 30.3% of referred cases did the hospital make contact with referral agents. Referral rates were highest from the predominantly coloured areas of the Cape Peninsula. The hospital cannot isolate itself from the community it serves and needs to support and guide referral agents in order to improve the utilisation of the hospital. Training of health professionals in order to increase expertise is a priority. A study of the total patient population would facilitate the understanding of hospital utilisation. Similar studies could be beneficial at other hospitals. PMID- 2218765 TI - Utilisation of outpatient services at Red Cross War Memorial Children's Hospital, Cape Town. AB - The demand for outpatient services continues to grow at Red Cross War Memorial Children's Hospital (RCCH). To determine current utilisation patterns, we conducted a 2-week survey in the outpatient department (OPD). In addition, we reviewed the RCCH Annual Reports for the period 1961-1988. Annual outpatient attendances have increased from around 42,000 in 1957 to their highest level ever; nearly 350,000 in 1988. This steady rise in outpatient attendance was stemmed during the 1970s by the expansion of health services in the greater Cape Town area, in particular the introduction of day hospitals. In general, blacks are utilising the OPD as a primary community hospital for the treatment of infectious and environmentally induced diseases. In contrast, the white outpatient profile is more characteristic of a tertiary referral centre, with a higher proportion of specialist clinic attendances. The utilisation patterns for coloured children are intermediate. Analysis of the residential address of patients and their presenting diagnoses indicates an urgent demand for primary health care services in the most recently settled and poorest suburbs of Cape Town, many of which are remote from the hospital. PMID- 2218766 TI - Paediatric trauma care. AB - Paediatric trauma care varies in different countries. In South Africa injury is the leading cause of death in the 5-14-year-old age group--1.5-3.8 times higher than in the USA. In 1978 the Child Safety Centre was established and prospectively collected data on paediatric injuries. The various types of injuries are discussed. Trauma is responsible for the highest percentage of years of life lost but the least amount of money is being spent on research and prevention of injuries. The Child Accident Prevention Foundation of Southern Africa has been constituted to research, prevent and reduce the risk factors of the injuries and to improve facilities for the injured child. PMID- 2218767 TI - Childhood near-drowning--a 12-year retrospective review. AB - The epidemiological findings in 107 patients admitted to Red Cross War Memorial Children's Hospital, Cape Town, between 1976 and 1987 with a diagnosis of near drowning are reported. Of these patients, 77% were less than 5 years of age (ratio of boys to girls 2.1:1) and 46% of accidents occurred in swimming pools, 18% in buckets and only 9% in the sea. The high percentage of bucket near drownings is unique in published medical reports; this appears prevalent in socially disadvantaged communities. Seventy-six per cent of the children were normal on discharge from hospital, 12% died and 6% had neurological damage. In 6% the final outcome was not known. These results are in keeping with other hospital based studies. Preventive strategies are discussed and the need for further research highlighted. PMID- 2218768 TI - Childhood near-drowning--factors associated with poor outcome. AB - Anoxic cerebral damage is the limiting factor in recovery from near-drowning accidents. This study reports factors associated with poor outcome in 100 near drowned patients admitted to the Red Cross War Memorial Children's Hospital from 1976 to 1987. The study was designed as a retrospective folder search. Children with fixed dilated pupils, flaccidity, decerebrate or decorticate posturing, or clinical signs of cerebral oedema are more likely to have a poor outcome. Patients with metabolic acidaemia and those requiring cardiopulmonary resuscitation in the emergency room or subsequent mechanical ventilation also do poorly. Those requiring more aggressive management can be identified and a more accurate working prognosis may be possible in the hours after the accident. PMID- 2218770 TI - Treatment of erectile failure. PMID- 2218769 TI - The role of R. B. Thomson and E. P. Stibbe--brief heralds of the science of anatomy in South Africa. Part II. E. P. Stibbe. PMID- 2218771 TI - Arrhythmias in congestive cardiopathy. PMID- 2218772 TI - Spinal cord compression due to myeloma. PMID- 2218773 TI - Nasopalatine airflow resistance in awake subjects. PMID- 2218774 TI - White blood counts in radiation workers. PMID- 2218775 TI - Junk food and empty words. PMID- 2218777 TI - The future of medical education--locally relevant excellence. PMID- 2218776 TI - Spinal cord injury management in 1990. PMID- 2218778 TI - Risk factors for coronary heart disease in the Indians of Durban. AB - Coronary heart disease (CHD) is a major problem in migrant Indians throughout the world. In South Africa it has reached 'epidemic' proportions. A field survey was conducted among Indians in the metropolitan area of Durban to determine the prevalence and known risk factors for CHD. In a study of 778 subjects aged 15-69 years (408 men), 15.3% (sex and age adjusted 13.4%) had a history of CHD. The important risk factors in men were hypercholesterolaemia, hypertriglyceridaemia, diabetes, and smoking, and in women diabetes, hypercholesterolaemia, and hypertriglyceridaemia. The minor risk factors were hyperuricaemia, sedentary occupation, obesity in women and a positive family history of CHD. A study of the major risk factors leading to CHD showed that 52% (sex and age adjusted 45.5%) had at least one major risk factor at the higher (level A) and 68% (sex and age adjusted 61.9%) at the lower (level B) risk levels. Diabetes mellitus was strongly associated with a positive history of CHD. In 47.6% (sex and age adjusted 48.2%) of the total group resting ECG abnormalities were found that could be coded. Because of the severe nature of CHD in the migrant Indian, an immediate and intensive programme of primary prevention of CHD risk factors should be instituted. PMID- 2218779 TI - Captopril in hypertensive black men in southern Africa. AB - A group of 55 black men with mild or moderate hypertension who were being treated with methyldopa, prazosin, and a thiazide diuretic in combination with sotalol, were studied before and after changing their treatment to captopril and a thiazide diuretic. The level of blood pressure control was similar in the 11 men with mild hypertension but the 44 men with moderate hypertension were less well controlled with captopril and a thiazide diuretic. In the men with moderate hypertension the mean increase in the systolic blood pressure after the change in treatment was 4.7 mmHg (not significant) and in the diastolic pressure 6.2 mmHg (P less than 0.02). The mean blood pressure was higher during treatment with captopril in 37 men and lower in 18 men (P = 0.01). Thirty-seven men found both regimens acceptable and 33 of these men preferred the captopril regimen; however, 15 men said they did not like the captopril regimen while only 4 men did not like the methyldopa/prazosin regimen (P less than 0.01). Side-effects from the captopril regimen were reported by 18 of the men and from the methyldopa/prazosin regimen by 6 men (P less than 0.02). It was concluded that the captopril/thiazide regimen was less effective than the methyldopa/prazosin/sotalol/thiazide regimen for the control of moderate hypertension in this population of black men. Although the men who liked both regimens preferred the captopril regimen, that regimen was associated with significantly more side-effects and was disliked by more of the men than was the methyldopa/prazosin regimen. PMID- 2218780 TI - Long-term efficacy and safety of sustained-release diltiazem in the treatment of hypertension. AB - The long-term efficacy and safety of sustained-release diltiazem (Tilazem; Parke Davis) were evaluated. A total of 27 young, physically active patients with hypertension were followed up for 17 months. On a dosage of 90 mg twice daily, adequate blood pressure reduction was obtained in 23 patients (85%). No adverse effects were noted. PMID- 2218781 TI - Indoramin in the treatment of pregnancy hypertension. A placebo-controlled trial comparing the efficacy of indoramin with alpha-methyldopa. AB - A placebo-controlled trial was used to assess the antihypertensive efficacy of indoramin in the management of pregnancy hypertension. Sixty patients were recruited into the study and only 17 attained satisfactory blood pressure control. In the doses of drugs administered indoramin was not shown to be more effective than alpha-methyldopa. PMID- 2218782 TI - Can we predict and/or prevent type I diabetes? AB - The highest risk for the development of type I diabetes resides with first-degree relatives of the diabetic proband, this risk being in the order of 2.9%, 6.6% and 4.9% for parents, siblings and children of the proband, respectively. The major genetic markers associated with the development of insulin-dependent diabetes mellitus (IDDM) is the possession of the HLA alleles DR3/DR4 and more recently the absence of aspartate in the 57th position on the beta-chain of the HLA DQ gene (HLA DQ beta Asp 57 negative). The most important auto-immune marker for predicting preclinical IDDM is the presence of high titres (greater than 40 Juvenile Diabetes Foundation units) of islet cell antibodies (ICA), while the finding of insulin auto-antibodies (IAA) is a good predictive marker in children less than 5 years of age. The presence in a susceptible individual of ICA plus IAA is a better predictor of impending IDDM than the presence of either of these two markers alone. Antibodies which precipitate an islet membrane protein (MW 64K) are highly sensitive and specific markers of preclinical IDDM. The presence of 64K antibodies may well be the most important predictive marker of impending IDDM in the future. The progressive decline of the first phase of insulin secretion in response to an intravenous glucose challenge is associated with the onset of IDDM within 18 months. Of the immunotherapeutic agents at present used in clinically manifest IDDM, azathioprine has been shown to be ineffective in increasing the remission phase, while the value of nicotinamide is controversial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2218783 TI - Malaria at Johannesburg Hospital. A retrospective study. AB - A total of 43 patients diagnosed as having malaria were admitted to Johannesburg Hospital during 1988; 40 (94%) were infected with Plasmodium falciparum. Only 26 patients (60%) were recorded as having used prophylaxis of any kind; chloroquine alone and in combination was used as prophylaxis by 17. Patients were treated with quinine (alone or in combination) in 67% of cases. In 42% of patients chloroquine-resistant malaria was considered a possibility. PMID- 2218784 TI - Lactose maldigestion--age-specific prevalence in black and Indian children. AB - A study was performed to determine the prevalence and age of onset of primary lactose maldigestion in healthy black and Indian children, and to determine whether this was of clinical significance. More black (22 of 44-50%) than Indian children (10 of 45-22.2%) had lactose maldigestion (P less than 0.02), the development of which was age-related and occurred earlier in blacks than in Indians; 6 of 19 black children less than 5 years old (31.6%) were lactose maldigesters, compared with 8 of 10 (80%) over 10 years old, while only 1 of 16 Indian children aged under 8 years (6.3%) were maldigesters, compared with 5 of 13 (38.5%) aged over 10 years. Most children had a very low intake of milk and lactose maldigestion was of no clinical significance to them. PMID- 2218785 TI - The snacking habits of white preschool children. AB - Three-day estimated dietary records were kept for 194 white 3- and 4-year-old children to determine and evaluate the extent, nature and quality of their snacking. All but 1 child ate between meals, with morning and afternoon snacking being favoured in terms of frequency and quantity. Soft drinks were consumed most frequently, followed by fresh fruits and fruit juices, sweets and chocolates, milk and sugar. Between-meal eating contributed more than one-third of the average day's energy and approximately one-quarter of most vitamins and minerals to the children's diets. Foods eaten between meals were, however, significantly less nutrient-dense than mealtime foods. Non-basic foods supplied more energy to the diet than any of the five basic food groups, but minimal quantities of micronutrients. Sugar consumption, mostly in the form of sugary foods and drinks, was high, but was not consumed exclusively between meals. Such children should be encouraged to make more use of basic commodities, particularly when snacking. PMID- 2218786 TI - Toxic cannabis psychosis is a valid entity. AB - One hundred black men admitted to hospital with acute psychiatric symptoms were investigated for the presence of urinary cannabis metabolites in order to delineate the psychiatric role played by 'dagga', the potent South African cannabinol, in the study population and to determine the diagnostic value of the entity 'toxic psychosis (dagga)'. Cannabinoids were present in 29% of patients, and 31% were discharged with a diagnosis of toxic psychosis (dagga). Clinical and demographic material was gathered for all patients and no consistent differences were found between dagga-positive and dagga-negative patients or toxic dagga psychotic patients and 'functional' psychotics other than a history of recent dagga use and the dagga screening test result. The latter measure was found to be both more sensitive and more specific than the history of dagga use alone. The findings support the routine use of a simple screening test for dagga in the sample population studied. The study demonstrated the heterogeneous nature of the toxic dagga psychosis syndrome by documenting a variety of different clinical presentations, which included schizophrenia (42%), paranoia (26%), maniform psychosis (16%) and organic psychosis (16%). PMID- 2218787 TI - Prenatal ultrasonographic diagnosis and successful management of mediastinal teratoma. A case report. AB - A case of mediastinal teratoma, diagnosed in utero by realtime ultrasonography during a late 3rd trimester evaluation of polyhydramnios, is described. Prompt respiratory assistance to the infant at birth and early surgical intervention led to a successful outcome. PMID- 2218788 TI - Symptomatic rubella re-infection in early pregnancy and subsequent delivery of an infected but minimally involved infant. A case report. AB - A case of serologically proven symptomatic rubella re-infection in early pregnancy in a healthy multigravida who had been successfully vaccinated is reported to illustrate that the risk to the fetus is considerably less than with primary infection. The infant was infected, as evidenced by specific IgM in cord blood, but had no stigmata of congenital rubella at birth. Growth retardation was apparent at 6 months and hearing loss, not necessarily due to rubella, was detected at 8 months. Rubella re-infection, which may now be distinguished serologically by the urea degradation test from primary rubella, need not necessarily be an indication for termination of pregnancy. PMID- 2218791 TI - Weight information on the 'Road to Health' card inadequate for growth monitoring. PMID- 2218790 TI - Tetanus--a preventable disease. PMID- 2218789 TI - The healing bird. AB - The legend of the caladrius, a bird with prognostic and healing powers, first appeared in early Indian writings as the haridruva--a yellow bird that cured jaundice. In classical Greek mythology it was a nondescript bird but in the medieval bestiaries it became pure white. The caladrius is used in the coats of arms of the South African Medical and Dental Council and also the Medical University of Southern Africa. These appear to be the first use of this medically significant bird in modern heraldry. PMID- 2218792 TI - Medical surveillance in the workplace. PMID- 2218793 TI - Medical surveillance in the workplace: overview. AB - Medical surveillance in the workplace is the systematic collection and evaluation of employees' health data to identify specific instances of illness or health trends suggesting an adverse effect of workplace exposures on employees' health. This process is coupled with actions to reduce hazardous workplace exposures, as reviewed in this issue. PMID- 2218794 TI - Guidelines for medical screening in the workplace. AB - This chapter deals with general principles of conducting medical examinations to detect adverse health effects of workplace exposures and thereby prevent occupational disease or slow its progression. Much of the discussion is most relevant to screening for effects of chemical hazards, but many of the principles presented apply to physical and biological hazards as well. Procedural and administrative aspects of workplace medical examinations that are not "exposure specific" and are applicable to all medical programs are reviewed. PMID- 2218796 TI - Role of industrial hygiene in medical surveillance. AB - The industrial hygienist and the occupational physician comprise a team that can effectively recognize and evaluate employee exposures to workplace-generated contaminants. At the most basic level, the industrial hygienist performs the exposure assessment, and the occupational physician develops the medical surveillance program. The actual mechanisms for assessing employee exposures and ultimately implementing a medical surveillance program are complex and are detailed in this paper. PMID- 2218795 TI - Medical surveillance in the workplace--legal issues. AB - With increased medical surveillance comes increased concern about the legal and ethical issues that surround it. This chapter addresses five major issues surrounding medical surveillance in the workplace. PMID- 2218797 TI - Rhythmic variations in medical monitoring tests. AB - Medical surveillance must be done with an awareness that virtually all physiological functions exhibit regularly recurring rhythmic variations. These rhythms, often termed "biological rhythms," and their biological effects are reviewed in this paper. PMID- 2218798 TI - Biological monitoring. AB - It is important to distinguish biological from medical or health monitoring because the submission of a biological specimen often leads to the assumption of the part of workers and also health professionals that health effects are being measured, and that measurement exceeding a reference value indicates disease rather than exposure or health risk. This chapter briefly reviews the basic principles of biological monitoring, focusing primarily on its role within medical surveillance. PMID- 2218799 TI - Medical surveillance for pulmonary endpoints. AB - The institution of workplace medical surveillance for pulmonary endpoints assumes the following conditions: that occupational lung diseases can be detected in early or preclinical stages; that early detection with appropriate intervention can lead to reduced morbidity; and that early detection and appropriate intervention are both feasible. The author of this chapter points out that, unfortunately, very few occupational settings meet these conditions. PMID- 2218800 TI - Medical surveillance for workplace hepatotoxins. AB - In contrast to clinical practice, the objective of medical surveillance in a workplace population with potential exposure to hepatotoxins is to detect people with occupation-associated liver dysfunction who either have or are at risk for developing clinical disease. Ideally, medical surveillance tests for hepatotoxicity should have, either alone or in combination, a high positive predictive value. PMID- 2218801 TI - Medical surveillance for renal endpoints. AB - The ability to monitor exposed workers for early evidence of nephrotoxicity facilitates efforts at secondary prevention. When this monitoring identifies previously unrecognized or unappreciated risk factors and leads to their elimination from the environment of future workers, the more desirable goal- primary prevention--may be realized. PMID- 2218802 TI - Medical surveillance for neurologic endpoints. AB - Except for screening for noise-induced hearing loss, medical surveillance for neurologic disease in the workplace has not been done on a routine basis in the past. In the future, however, as occupational medicine focuses increasingly on the detection of preclinical effects of exposure and strategies to prevent such exposures, medical surveillance for neurologic disease will become a necessity. PMID- 2218803 TI - Medical surveillance and biomonitoring for occupational cancer endpoints. AB - Medical surveillance for carcinogens refers to the use of medical history, physical examinations, and laboratory examinations to detect medical effects of exposure to cancer-causing agents. Biomonitoring for carcinogens, in contrast, involves testing for changes in DNA or chromosomes, presence of mutagens in body fluids, or presence of markers of exposure in cells. This article evaluates the current medical surveillance and biomonitoring techniques to assess their utility as measures of potential exposure to and effects of carcinogens in the workplace. PMID- 2218805 TI - Drug testing in the workplace. AB - The author first discusses drug use in society at large versus the workplace, then focuses on the issue of drug testing in the workplace. Goals of and approaches to drug testing are discussed, legal issues highlighted, testing procedures detailed, testing programs introduced, and finally the role of employee assistance programs reviewed. PMID- 2218804 TI - Medical surveillance for melanoma at the Lawrence Livermore National Laboratory. AB - Following identification of an unusual cluster of cases of malignant melanoma among laboratory employees at this national facility, several studies were done to provide further understanding and solutions to the problem. This paper discusses the Laboratory's response, including the educational campaign and institution of self-examinations. Experience with the melanoma surveillance program to date reinforces its validity. PMID- 2218806 TI - Job-exposure matrices in epidemiologic research and medical surveillance. AB - In summary, job-exposure matrices consist of a number of related methods for the assessment of occupational exposures that have been adapted to a variety of research settings. The potential advantages of job-exposure matrices include the avoidance of some forms of bias and enhanced statistical power to detect associations. However, misclassification of exposures may be problematic, and the sensitivity of this approach has not been consistently shown to be greater than that of conventional methods of exposure assessment based upon interviews of subjects. The job-exposure matrix approach may be especially useful for studies involving the historical reconstruction of exposures at industrial sites. More attention needs to be given to improving the completeness and accuracy of employment history information and to the validity of exposure estimates over time. Future developments may include the increased availability and utilization of quantitative exposure estimates such as environmental air sampling and personal monitoring data. Although job-exposure matrices are generally associated with case-control study designs, they may also be useful in prospective studies. Thus, job-exposure matrices are a potentially valuable addition to epidemiologic research methods which, if applied judiciously, may contribute to etiologic research and to the identification and control of hazardous exposures in the workplace. PMID- 2218807 TI - [The economic and sociomedical efficiency of innovations in the practice of health protection]. AB - The article discusses techniques for assessing the economic and medico-social efficiency of innovations introduced into health care practice starting from the example of a new procedure (prodigiosin inhalations) in prevention of ENT disorders and of influenza in preschool children. The analysis bears on the role and importance of evaluations of this type in the implementation of scientific findings, as well as in restructuring the health care sector and reorienting biomedical research. The authors contend that the expanding area of innovation use does not trigger more than insignificant rises in costs (costs allocated to scientific research, for instance), whereas cost containment is almost directly proportional to the expanding applications. It can, therefore, be concluded that imposing limitations and delays in the implementation of efficient innovations bars cost savings and diminishes the actual economic efficiency of biomedical research. PMID- 2218808 TI - Randomized clinical trials and public health: a review of current trends. PMID- 2218809 TI - [Trends in the improvement of the medical documentation system]. AB - The paper reports on the general and specific functions of medical records, as well as on the need to improve medical recording and the circulation of medical records in health units. The economic medical and social advantages of keeping accurate records are highlighted. Recent breakthroughs in information science permit unifying and standardizing medical records, making them more problem oriented, developing technical equipment and extending its use in archives, expanding the role of the computer in clinical recording. PMID- 2218810 TI - [The social and hygienic aspects in the protection of the health of forest industry workers]. AB - The study of social and hygiene aspects in the industry of forest exploitation permitted to point out the changes that occurred in the field of mechanization and automation of production processes, which radically influenced the working conditions and characteristics, as well as the health indices. The study approaches some economic, social and hygiene problems. Proposals are made regarding the improvement of medical care organization for workers, for example the drawing up of a complex programme of prophylaxis of diseases in the enterprises for wood industrialization and of utilization of the computation technique. PMID- 2218811 TI - Evaluation of risk factors for essential arterial hypertension in industrial and school environments. PMID- 2218812 TI - Domestic accidents: theoretical controversies. PMID- 2218813 TI - [A psychological profile of subjects from industrial sectors with cardiovascular diseases interviewed via the H. J. Eysenck questionnaire]. AB - Authors in the literature are unanimous in considering type A personality as an individual characteristic susceptible to cardiovascular risk. The latter, in its turn, is regarded, after H. J. Eysenck [4], as an association of the scores of extroversion and neurosis. Starting from this assumption, we set out to outline a profile of the cardiovascular patient using the "Eysenck" questionnaire. The study population included 126 industrial workers compared to a matching control set. The resulting profile displayed neurotic components within an ego perpetually frustrated in its needs of well-being, emotional satisfaction and rewarding social relations (-1,dark blue, Luscher colour test in its shortened variant). Stress and introversion foster neuroticism and encourage the ego in its compulsive quest for autonomy, "eccentric" behaviour in actual situations and egocentric attitudes in reserve. Findings suggest that the "H. J. Eysenck" test for introversion-extroversion and neuroticism, as well as the Luscher colour test (the shortened variant) are likely to be useful predictive tools in cardiovascular disease. PMID- 2218814 TI - [The thermogenic function of the large intestine and diverticulosis]. PMID- 2218815 TI - Alcohol--risk factor in prenatal pathology (alcohol embryo- and fetopathy). PMID- 2218816 TI - Results of conservative surgery and radiation therapy for breast cancer. AB - For stage I or II breast cancer, conservative surgery and radiation therapy are as effective as modified radical or radical mastectomy. In most cases, cosmetic considerations and the availability of therapy are the primary concerns. The extent of a surgical resection less than a mastectomy has not been a subject of a randomized trial and is controversial. It appears that removal of a quadrant of the breast for small lesions is safe but excessive. Using histologic findings in the biopsy as a guide, it may be possible to limit the breast resection to gross tumor removal for most patients while using wider resections for patients with an extensive intraductal component or for invasive lobular carcinoma. It also appears that excluding patients from breast conservation on the basis of positive margins on the first attempt at tumor excision may be unnecessarily restrictive. Although patients with an extensive intraductal component or invasive lobular carcinoma should have negative margins, it appears that a patient with predominantly invasive ductal carcinoma can be treated without re-excision if all gross tumor has been resected and there is no reason to suspect extensive microscopic disease. Patients with indeterminate margins should have a re excision. Axillary dissection provides prognostic information and prevents progression of the disease within the axilla. Axillary dissections limited to level I will accurately identify a substantial number of patients who have pathologically positive but clinically negative nodes. When combined with radiation therapy to the axilla, a level I dissection results in a limited number of patients with progressive axillary disease. Patients with pathologically positive axillas and patients at particularly high risk for systemic disease because of the extent of axillary node involvement can be identified by dissections of levels I and II. Radiation therapy can be avoided safely in patients who have pathologically negative axillas by level I and II dissection. There appears to be no advantage to routine dissection of level III lymph nodes. Lymphedema of the arm and breast increases with more extensive dissections and with radiation therapy. PMID- 2218817 TI - Role of mastectomy in breast cancer. AB - The surgical management of breast cancer continues to evolve in an attempt to define the ideal line between therapeutic efficacy and morbidity. It is clear that breast cancer is a biologically heterogeneous group of diseases, and no single hypothesis explains its behavior. The surgical options proposed to the individual patient must draw from the experience of retrospective clinical studies and prospective randomized trials in an attempt to optimize the treatment plan. Most patients without distant disease are eligible to consider mastectomy, which can accomplish excellent local control and significantly improve survival for earlier stages of disease. However, breast conservation remains an appropriate alternative for a carefully defined subset of patients. Today, with early-stage disease, no patient need leave the operating room without a breast. Recent advances in reconstructive surgery make mastectomy with immediate reconstruction or limited resection plus axillary dissection with postoperative radiation therapy the two principal treatment choices available. Future studies will focus on the integration of other treatment modalities. Clinical research into the use of preoperative chemotherapy to downstage the disease to permit less extensive surgery is of interest. Recent application of molecular biologic techniques such as oncogene analysis, cytogenetic studies, proliferative indices, and the highly sensitive detection of distant micrometastases using monoclonal antibodies may assist in the design of innovative approaches to surgery, radiation therapy, and systemic drug treatment. These advances show great promise for improving the quality of life and the cure rate for patients with breast cancer. Today, surgical treatment options have evolved that fulfill some of the objectives outlined by Dr. James Ewing of Memorial Hospital some 50 years ago. His concerns about breast cancer remain as relevant today as they were half a century ago: "I have drawn the impression that in dealing with mammary cancer, surgery meets with more peculiar difficulties and uncertainties than with almost any other form of the disease. The anatomical types are so numerous, the variations in clinical course so wide, the paths of dissemination so free and diverse, the difficulties of determining the actual conditions so complex, and the sacrifice of tissues so great, as to render impossible in the majority of cases a reasonably accurate adjustment of a means to an end." PMID- 2218818 TI - Selection of breast-preservation therapy for primary invasive breast carcinoma. AB - Breast-preservation treatment for primary breast cancer should not be used for all women. Women frequently excluded from consideration for such treatment or who choose not to have it may be elderly and not concerned about cosmetic appearance or live at a distance so that 6 weeks of daily trips to radiotherapy would be inconvenient or even impossible. Also, if radiotherapeutic expertise or facilities are not available, a breast-preservation program is difficult. In Massachusetts, a full course of just over 6000 cGy (4500 cGy to the whole breast and a 1600-cGy local boost) costs roughly $6000. Thus, breast preservation is more expensive than mastectomy even with reconstruction, as patients still frequently require a hospital admission with general anesthesia for an axillary dissection. Although insurance policies cover such expenses, patients who do not have insurance or have inadequate coverage may find the extra expense of the breast-preservation technique burdensome or impossible. Women with a small breast and a proportionately large cancer may have an unsatisfactory cosmetic outcome after appropriate lumpectomy. The cosmetic result in such patients frequently cannot be predicted beforehand; this fact adds emphasis to the need for a two step process of lumpectomy and then re-evaluation of the cosmetic outcome as well as pathologic features for decisions regarding breast preservation. Finally, women may have strikingly different attitudes toward breast preservation than expected by the surgeon. For some women, the urge to preserve the breast is so strong that they will accept virtually any risk to achieve this option, whereas for other women, the constant anxiety about a recurrence or undergoing radiation therapy is traumatic enough that they readily accept mastectomy. In our referral surgical oncology practice, roughly 60% of patients are currently treated with breast-preservation techniques; the remainder undergo mastectomy, with immediate reconstruction in approximately three fourths of the cases. The proportion of patients who elect to have breast preservation depends greatly on local medical customs and attitudes; the radiotherapeutic skills available; women's attitudes, which frequently are dependent on the local press and publicity; and the surgeon's interest and enthusiasm for such a program. There is no appropriate proportion of patients who should be treated by breast-preservation techniques, but clearly, the proportion of patients so treated increases with experience, acceptability, publicity, and availability. Thus, the selection of breast preserving therapy for individual patients is a result of an extraordinary array of factors that need to be considered in each patient.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2218819 TI - Selection of therapy for stage III breast cancer. AB - Locally advanced breast cancer is a heterogenous group including both operable and inoperable lesions. Local surgery or radiation alone produces poor survival rates, indicating micrometastases at diagnosis. Systemic chemotherapy as part of multimodality regimens has increased the length and rate of disease-free survival. PMID- 2218820 TI - Adjuvant chemotherapy of breast cancer. AB - Many women will not be cured of breast cancer by even the best early detection and surgical techniques because of micrometastases present at diagnosis. Adjuvant therapy has extended the disease-free interval for most patients and lengthens overall survival for many. Combination chemotherapy has become the standard form of adjuvant treatment for premenopausal women with breast cancer and positive lymph nodes after primary therapy. With minimal toxicity, disease-free and overall survival are improved. Results are less impressive or less clear-cut for postmenopausal women or any woman with negative lymph nodes. Long-term toxicities of adjuvant chemotherapy may include second malignancies and cardiac dysfunction. Although these complications probably are rare, they must be considered seriously when weighing chemotherapy for patients in whom its benefits may be slight. Innovations likely to become standard in adjuvant therapy decision making include risk assessment with new prognostic indicators (growth fraction, oncogene expression) and investigation of dose intensification using bone marrow growth factors and autologous stem-cell support. PMID- 2218821 TI - Adjuvant antiestrogen therapy for breast cancer. Past, present, and future. AB - Laboratory investigations using animal models of breast cancer growth have indicated that the antiestrogenic compound tamoxifen is a tumoristatic agent. It is therefore effective in suppressing, rather than destroying, the breast tumor. Its use as an adjuvant in breast cancer management has been successful, with a proportion of women benefiting from long periods of tamoxifen treatment. All the initial studies recruited postmenopausal women, but tamoxifen is now proposed for the treatment of premenopausal women for an extended time. Naturally, there are many aspects of the toxicology of tamoxifen to consider; however, careful monitoring of clinical trials will determine the safety of the drug for the general patient population. PMID- 2218823 TI - Reconstruction after mastectomy. AB - Advances in materials and techniques, especially those involving transposition of muscle and skin flaps, have made breast reconstruction possible for most women who undergo mastectomy for breast cancer. The availability of this option can alleviate the breast and chest wall deformity that results from virtually all local treatment of breast cancer. It is essential that the reconstruction surgeon be part of the breast cancer management team from the beginning of treatment planning and that this surgeon work closely with the general surgeon, medical oncologist, and radiation therapist as well as the adjunctive treatment team members. The patient's clinical status and the type of local treatment will be significant determinants of the reconstructive options. For women with stage I breast cancer, these decisions may be based largely on the oncologist's local and adjunctive therapy procedures and the woman's desire to proceed or delay. For women with systemic disease, all members of the breast management team may need to agree on the advisability and timing of reconstruction. Central to all of the numerous decisions described in this paper regarding the timing, type, and extent of breast reconstruction is the primary goal of the entire team: the best possible management of the breast cancer itself. The promise of attractive, symmetric, and natural appearing breasts, complete with a symmetric nipple areolar complex, has eased somewhat the diminishment of self-esteem and the threat to femininity that can accompany the loss of a breast. By lowering fear, the widely recognized availability of breast reconstruction may encourage more women to monitor their breasts and seek diagnosis of changes and may influence selection of the type of local treatment if cancer is detected. Because of the psychological and cultural significance of the breast, the reconstructive surgeon must be particularly sensitive to the psychological and aesthetic expectations of the patient. Even in those patients with metastases and limited life expectancy, breast reconstruction can enhance the quality of life. PMID- 2218822 TI - Management of local and regional recurrence after mastectomy or breast-conserving treatment. AB - Locoregional failures after primary treatment for breast cancer include a diverse group of lesions that represent different categories of failures with various prognoses. Although patients with chest wall recurrences and regional nodal failures after traditional radical surgery have a poor prognosis, many patients can still achieve a significant degree of palliation and even long-term survival or cure with carefully orchestrated multimodal treatment. In patients who have breast failures after breast-conservation surgery and radiation, long-term salvage and cure can be achieved for the majority with prompt detection and appropriate treatment, which, like treatment for primary breast cancer, includes a consideration not only of local control but also of the risk of subsequent systemic failure and its need for treatment. PMID- 2218824 TI - Bilateral breast cancer. AB - A second primary breast cancer in the opposite breast can be either synchronous or metachronous. The majority are metachronous. A woman who has had breast cancer has a fivefold increase in risk for a second breast cancer. Additional risk factors include multifocal cancer, lobular carcinoma in situ, and an original cancer at an early age with long survival. Lobular carcinoma in situ is predominantly a marker for the subsequent development of a second primary breast cancer. The incidence of synchronous bilateral cancer is approximately 1% to 2% and that of metachronous cancer 5% to 6%. The cancer can be invasive or noninvasive. Mammography has increased the number of synchronous cancers found but not the overall incidence. The incidence of invasive cancer detected by random biopsy of the opposite breast is not high enough to justify routine adoption of this procedure. The remaining breast must be followed for the remainder of the patient's life by physical examination and annual mammography. The treatment of the secondary primary breast cancer should be that appropriate for the stage of the disease. The prognosis for the woman with a second primary breast cancer is quite favorable and is dependent on the stage of both the first and the second cancer. PMID- 2218825 TI - Breast cancer during pregnancy and lactation. AB - Breast cancer is the most frequently seen cancer in pregnancy and lactation, but the incidence is low, the disease being seen in approximately 0.03% of pregnancies. Only 1% to 2% of breast cancer overall is diagnosed during pregnancy or lactation. There is no evidence to implicate pregnancy or lactation in either the etiology or the progression of breast cancer. Careful breast examination early in the pregnancy is very important to find solid masses that require biopsy before breast engorgement hides them. Therapeutic options vary, depending on the stage of disease and the stage of the pregnancy. Operable disease in the first 6 to 7 months of the pregnancy should be treated by mastectomy, as irradiation is contraindicated. Late in the pregnancy, a lumpectomy and axillary dissection can be done, with irradiation being delayed until after delivery. General anesthesia is safe if the usual precautions are taken to compensate for the physiologic changes induced by pregnancy. Unfortunately, delay in diagnosis is common, and 70% to 89% of patients with operable primary lesions have positive axillary lymph nodes. Late stage appears to be the only reason for the generally worse prognosis in these patients, as stage for stage, they have a course similar to that of nonpregnant patients. Adjuvant chemotherapy can be considered late in the pregnancy but should usually be delayed until after delivery. In patients with locally advanced or metastatic cancer diagnosed early in the pregnancy, for whom both chemotherapy and radiation therapy would normally be recommended, consideration must be given to termination of the pregnancy. There is no evidence that termination of pregnancy improves the outlook for the patients, but it does permit standard aggressive therapy in advanced disease. PMID- 2218826 TI - Male breast cancer. AB - Male breast cancer is uncommon but important. The diagnosis is easily made by breast biopsy, and patients are presenting earlier in the course of the disease than in the past. Despite this, patients are often first seen with tumors that have metastasized to the axillary nodes, which markedly decreases the survival rate. Therapy of localized disease includes simple excision, modified radical mastectomy, and radical mastectomy, but there is no consensus for which operation is appropriate. Radiation therapy should be strongly considered in patients with metastases to the axillary nodes, but the role of adjuvant hormonal therapy or chemotherapy is unclear. For treatment of disseminated disease, tamoxifen seems to be replacing orchiectomy. The favorable response rate, especially in patients with estrogen-receptor-positive tumors, the lack of side effects, and the high level of patient acceptability make it an attractive therapeutic choice. PMID- 2218827 TI - Clinical problems in follow-up of patients after conservative surgery and radiotherapy. AB - Patients treated with conservative surgery and radiotherapy for early-stage breast carcinoma are at risk of developing an ipsilateral breast recurrence for a long period. Fortunately, few such patients present with an inoperable recurrence or simultaneous distant metastases. Salvage rates are high and may be improved by early detection. Although usually unambiguous, physical examination of the treated breast may reveal changes attributable to surgery and radiotherapy that can mimic a recurrent cancer. There also is substantial overlap in radiologic appearance between benign and malignant lesions. It may be necessary to perform a biopsy when there is a question of recurrence. Careful life-long follow-up of patients thus is a critical part of their care. PMID- 2218828 TI - Trends in primary breast cancer management. Where are we going? AB - The treatment of cancer during any period has been based not on the whim of a clinician but on the therapeutic consequences of the dominant biologic model of the disease. Until the 1960s, the dominant model of breast cancer was of a disease that spread centrifugally along anatomic pathways, with time being the only determinant of prognosis. An alternative model, that of biologic determinism, posits that the outcomes of treatment are determined by the extent of microscopic dissemination that occurred before the tumor became detectable. This model, too, has flaws, and the author suggests that it is time for a Kuhnian paradigm shift. Breast cancer exhibits a heterogeneity of phenotypes resulting from one or perhaps two mutations. The multiple prognostic variables may be epiphenomena, expressing different degrees of amplification of a limited domain of the genome. PMID- 2218830 TI - Breast cancer: strategies for the 1990s II. PMID- 2218829 TI - Prognostic indicators in invasive breast cancer. AB - Tumor size and axillary lymph node involvement are the primary determinants of clinical course for most patients. Receptors for estrogen and progesterone are important additional prognostic factors for disease-free survival, overall survival, survival time after initial disease recurrence, and the likelihood of response to hormonal therapy. Histologic grading has merit as a prognostic factor, although poor reproducibility limits its broad application. Promising data have been emerging from the use of flow cytometry to analyze DNA content and proliferative rate. Patients with aneuploid tumors are more likely to have a shorter survival time than patients with diploid tumors. A high S-phase fraction also identifies a subset of patients at increased risk for early relapse. A combined index of ploidy and S-phase may be a more useful guide; together, diploidy and low S-phase identify a subgroup of node-negative patients at very low risk for disease recurrence. A number of oncogenes have been identified in breast cancer; amplification of the HER-2/neu gene or overexpression of the gene product may be an important prognostic indicator for node-positive patients. PMID- 2218832 TI - Synchronous carcinoma of the colon and rectum. AB - Reports on the incidence of synchronous carcinoma of the colon and rectum have varied from 2 to 11 per cent. The variability is a result of a lack of uniformity in criteria of diagnosis, differences in the population studied and differences in time period used. In this study, we evaluated the incidence and distribution of synchronous lesions during a recent time period before the use of colonoscopy became widespread. We reviewed the records of all patients with newly diagnosed adenocarcinoma of the colon and rectum who were operated upon at our institution between 1976 and 1981. In a total group of 1,000 patients of which 52 per cent were men, there were 54 patients or 5.4 per cent who had synchronous carcinomas. The group of patients with synchronous carcinomas were older than the group with nonsynchronous carcinomas (72.4 versus 68.8 years). There was also a higher incidence of associated benign polyps in the group with synchronous carcinomas (70 versus 30 per cent for a nonsynchronous carcinomas). The anatomic distribution of carcinomas of the colon and rectum in the group with synchronous lesions (111 in total) revealed a higher percentage of carcinomas located on the right side (29.7 versus 22.5 per cent), although the difference did not reach statistical significance. Synchronous carcinomas were located in nonadjacent segments of the colon in 37 per cent. There was no difference in stage between the groups with and without synchronous carcinomas. The preoperative identification of synchronous lesions by either colonoscopy or barium enema is important for the proper treatment of patients with carcinoma of the colon and rectum. Failure to locate these tumors may lead to the demise of the patient. PMID- 2218833 TI - Total parathyroidectomy and autotransplantation in hyperplasia of the parathyroid gland. AB - Hyperparathyroidism caused by multiple-gland hyperplasia has traditionally been treated by subtotal parathyroidectomy. Excellent results have been reported by some, particularly in primary hyperparathyroidism, but other have reported a significant incidence of recurrent hyperparathyroidism. Since 1979, we have chosen to avoid the possibility of remedial exploration of the neck and its attendant risks by treating all patients with primary and secondary hyperplasia with total parathyroidectomy and heterotopic autotransplantation. A total of 20 patients were studied. There were no failures of grafts and no operative complications. We conclude that this procedure is a reliable and safe alternative in the treatment of primary or secondary hyperplasia of the parathyroid gland. PMID- 2218831 TI - Broad spectrum penicillin as an adequate therapy for acute cholangitis. AB - In a previous study of patients with acute cholecystitis, we demonstrated equal efficacy with a broad spectrum penicillin (piperacillin) and a penicillin plus amino-glycoside combination. Whether a single agent broad spectrum penicillin is adequate treatment for more severe infections, such as acute cholangitis, however, is still unclear. We, therefore, conducted a three center, prospective, randomized trial to determine whether or not a broad spectrum penicillin alone is adequate therapy for patients with acute cholangitis. During a 36 month period, 96 patients with sepsis and biliary obstruction were randomly assigned to receive either piperacillin (n = 49) or ampicillin plus tobramycin (n = 47). The two groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. The incidence of blood cultures with positive results (20 versus 21 per cent) and underlying malignant lesions (51 versus 62 per cent) was also similar between the two groups. The percentage of patients with a clinical cure or significant improvement was the same in the two groups (69 versus 70 per cent). However, there was a significant difference in the cure rate between patients with benign and malignant biliary obstructions (83 versus 59 per cent, p less than 0.01). No significant differences were noted between the two antibiotic groups with respect to drug toxicity, but patients with malignant conditions were more prone to antibiotic related toxicities (2 versus 19 per cent, p less than 0.05). These data suggest that outcome of treatment in patients with acute cholangitis is similar with either a broad spectrum penicillin or a penicillin plus aminoglycoside combination and is dependent upon the nature of the biliary obstruction. PMID- 2218834 TI - A comparison of hospital costs and morbidity between octogenarians and other patients undergoing general surgical operations. AB - The hospital costs and clinical results of 304 patients who were more than 80 years old and who underwent general surgical procedures were evaluated. The over all mortality rate was 14 per cent; 19.9 per cent occurred in patients admitted under emergency conditions as compared with 8.9 per cent that occurred in patients undergoing elective procedures (p less than 0.001). Seventy-nine per cent of the patients were discharged and 7 per cent required care in a skilled nursing facility. Survival rates were as good or better than standard life table survival rates for 80 year old patients. Costs were higher in those who were admitted under emergent conditions or who died in the hospital. Deaths were a result of complications of the primary disease rather than associated disease in most groups. Neither costs nor length of stay could accurately predict survival of individual patients. We concluded that health resources should be directed at treating problems, such as cholelithiasis, hernia or carcinoma, early before complications develop. PMID- 2218835 TI - Carcinoma of the thyroglossal duct. AB - A review of 39 instances of excision of a cyst of the thyroglossal duct performed at St. Paul Medical Center, Dallas, Texas, revealed two patients with carcinoma of the thyroglossal duct. A review of the English literature yielded 146 instances of this uncommon tumor. Eighty-four per cent were papillary adenocarcinoma of thyroid type and 5 per cent were squamous cell carcinoma. The patients were from six to 81 years old with a 2:1 female to male ratio. Metastatic disease to lymph nodes was noted in 11 per cent and invasion of overlying strap muscles was found in 4 per cent. Carcinoma of the thyroid gland occurred in 14 per cent. Preoperative diagnosis was rare. The Sistrunk procedure is recommended for initial surgical therapy with further surgical or adjuvant therapy dependent on associated clinical findings. Prognosis for carcinoma of the thyroglossal duct of thyroid type parallels that of carcinoma of the thyroid gland. PMID- 2218836 TI - A multifactorial analysis of mortality and morbidity in perforated peptic ulcer disease. AB - Perforated peptic ulcer disease remains a source of considerable morbidity and mortality, and the suggested methods of surgical therapy are diverse. We reviewed the course of 113 patients who were treated surgically and identified 14 factors that influenced the morbidity or mortality rates, or both. Multiple regression analysis showed that the number of coexisting medical conditions, a lower mean blood pressure level and the duration of acute perforation were independent risk factors for death, while age, use of a bronchodilator, a lower mean blood pressure level and the number of coexisting medical conditions correlated positively with all complications. A duodenal site was independently favorable with respect to all complications. The type of operation performed either simple closure, vagotomy and drainage or resection, did not influence morbidity or mortality. The most severely ill patients also did not benefit from any particular type of operation in the short term. Long term results were improved with definitive operation, as measured by the Visick classification and the need for reoperations. Definitive operations are recommended for virtually all patients with perforated peptic ulcer. PMID- 2218837 TI - Surgical management of islet cell dysmaturation syndrome in young children. AB - Islet cell dysmaturation syndrome (ICDS) encompasses the causes of infantile hyperinsulinemic hypoglycemia histologically described as islet cell hyperplasia, pancreatic adenomatosis and nesidioblastosis. Eleven infants underwent 14 pancreatic resections for ICDS from 1965 to 1990 at the University of California at Los Angeles Medical Center for severe hypoglycemia unresponsive to medical therapy. Seizures were the presenting symptoms of hypoglycemia in eight infants. Six patients had nesidioblastosis, four had islet cell hyperplasia and one patient had an adenoma with histologically normal pancreatic islet cells. Four neonates underwent 80 per cent pancreatic resection; three with nesidioblastosis required reoperation (90 to 95 per cent resection). Four older infants underwent 80 per cent pancreatic resection but required diazoxide for less than six months postoperatively. Three infants underwent 90 to 95 per cent pancreatic resection. None have required reoperation or postoperative medications. All infants are normoglycemic without pancreatic exocrine insufficiency and none had postoperative complications. Five infants had preoperative neurologic impairment, with three having severe retardation; all showed some improvement postoperatively, but only one infant now has normal findings on neurologic examination. Early diagnosis and aggressive surgical resection should minimize neurologic complications of the ICDS. PMID- 2218839 TI - Results of vein graft reconstruction of the lower extremity in diabetic and nondiabetic patients. AB - The results of 171 vein grafts of the lower extremity were evaluated. These were placed between January 1981 and December 1987 in 150 patients, 75 diabetic and 75 nondiabetic, to determine the influence of diabetes on the outcome of the procedure. One and four year patency rates were determined by a life table analysis. No statistical differences in primary patency were found between the patients with diabetes and those without diabetes for all indications of operations (one year, diabetic patients 95 +/- 3 per cent, nondiabetic patients 85 +/- 3 per cent; four years, diabetic patients 89 +/- 11 per cent and nondiabetic patients 80 +/- 12 per cent; p = n.s.). For those operated upon for salvage of the limb because of rest pain, ulceration or gangrene, patency in diabetic patients at one year approached a statistically significant advantage (diabetic patients 94 +/- 4 per cent versus nondiabetic patients 79 +/- 8 per cent; p = 0.056). We believe that arterial reconstruction of the lower extremity can be performed upon patients with diabetes with the same high degree of success for revascularization and salvage of the limb as can be accomplished in nondiabetic patients. This is true even though those with diabetes present with necrosis of the tissue and more often require bypass to distal tibial arteries. PMID- 2218838 TI - Immediate preoperative phlebotomy with autologous blood donation for aortic replacement. AB - The preferential use of autologous blood provided by phlebotomy can reduce the need for homologous blood transfusion in patients undergoing extensive elective operations. This blood is usually provided either by intraoperative isovolemic hemodilution or phlebotomy one to two weeks preoperatively. To minimize the intraoperative time delay or preoperative period between phlebotomy and operation required in these patients, we performed preoperative isovolemic hemodilution in 69 patients one to two days prior to elective aortic replacement for infrarenal aneurysmal disease. Patients underwent phlebotomy a mean of 0.57 +/- 0.01 liter of whole blood; volume was replaced with lactated Ringer's solution. Hematocrit levels decreased from a mean value of 42.9 +/- 0.4 per cent to 33.7 +/- 0.3 per cent. Mean intraoperative blood loss was 1.2 +/- 0.05 liters. Hemodynamic parameters (blood pressure, cardiac output, pulmonary capillary wedge pressure, central venous pressure, oxygen delivery and systemic vascular resistance) remained stable throughout the perioperative and intraoperative time periods. In addition, we evaluated the technical modification of exclusion aneurysmorrhaphy (n = 50) versus open aneurysmorraphy (n = 19) on reduction of intraoperative homologous blood transfusion in these patients. Seventy-two per cent (36 of 50) of patients whose aneurysms were excluded received no homologous blood intraoperatively. Blood loss was decreased in the excluded versus open aneurysmorraphy group, 920 +/- 90 milliliters versus 2,030 +/- 250 milliliters, as were homologous blood transfusion requirements, 175 +/- 35 milliliters versus 570 +/- 119 milliliters. Two patients died (2.9 per cent mortality rate), and there was no increase in morbidity. Surgical treatment of large aortic aneurysms is frequently performed on an urgent basis; thus, provision of autologous blood for this operation in a short period of time may be beneficial. Isovolemic hemodilution performed during the immediate preoperative period can reduce homologous blood requirements and be safely performed without adverse effects on mortality, morbidity and myocardial performance. Exclusion aneurysmorrhaphy may further reduce dependence on homologous blood. PMID- 2218840 TI - Nonendoscopic percutaneous gastrostomy. AB - Tight peritoneal adherence of the stomach to the abdominal wall as a prerequisite of percutaneous gastrostomy can be achieved by a newly developed cannula. It serves for puncture and fixation of the gastric wall. Thus, percutaneous gastrostomy can be established safely even in instances of an endoscopically nonaccessible stomach. Further applications of the device for the purpose of intestinopexy and facilitation of endoscopic procedures are being evaluated. PMID- 2218841 TI - Patterns of small intestinal injury with the argon beam coagulator. PMID- 2218842 TI - Use of the internal mammary vein for central venous access. AB - We have reported two instances requiring long term central venous access in which the more traditional access sites were no longer available. The use of the internal mammary vein has made it possible to easily obtain central venous access in these patients without thoracotomy. Also, based on the anatomy, we believe this to be superior to the intercostal venous approach, since the passage of the catheter is more direct, thus, avoiding the acute azygous arch angle and cumbersome positioning. PMID- 2218843 TI - Simple technique for securing ureteral stents during urinary diversion [corrected]. PMID- 2218845 TI - Evolution and future perspectives for reduced-size hepatic transplantation. AB - Reduced-size hepatic transplantation has evolved into a clinically useful procedure, particularly at institutions specializing in treating pediatric patients. It is being adopted by many of the hepatic transplantation institutions in the United States as a result of its effectiveness in providing a greater number of donors for small recipients and an outcome equal to full-size hepatic transplantation. It has led to the development of "split-liver" transplantation, which is at present not universally applicable because of its complexity, but could double the supply of donors available to small patients. It is also the precursor of orthotopic auxiliary transplantation, which could become the preferred method for treating children with metabolic diseases, but no structural changes, such as cirrhosis. Finally, the knowledge gained in reduced-size hepatic transplantation will inevitably lead to transplantation using living donors, which could completely alleviate the shortage of donors for small patients. PMID- 2218844 TI - Management of the pregnant patient with carcinoma of the breast. AB - The diagnosis of carcinoma of the breast during pregnancy poses a challenging dilemma. Although once regarded as incurable, recent reports reveal similar long term survival rates for pregnant and nonpregnant patients who have carcinoma of the breast. When referred to a surgeon, a pregnant woman with a suspicious mammary mass deserves an expedient histologic diagnosis; delay may jeopardize the chances of survival. Once the diagnosis is established, pregnant patients should be treated in a manner similar to nonpregnant patients because there is no evidence that carcinoma of the breast in pregnant women is biologically different than carcinoma of the breast in other premenopausal women. Fears of fetal exposure to radiation should not deter a physician from ordering appropriate preoperative diagnostic tests to stage the patients. Operation may be performed safely when general anesthesia is administered and postoperative adjuvant therapy should be administered when necessary. The involvement of multiple subspecialties in the management of these patients is highly recommended. PMID- 2218846 TI - Response of spinal cord blood flow and motor and sensory evoked potentials to aortic ligation. AB - To produce spinal cord ischemia in the lamb, ligation of the thoracic aorta was performed for 15, 30, and 45 minutes in three animals each. Spinal cord blood flow and motor and sensory evoked potentials were measured before, during, and after aortic ligation. Ischemia with a blood flow of zero during ligation was encountered in the thoracic and lumbar cords, followed by hyperemia upon release of the ligature. Both somatosensory and motor evoked potentials were obliterated during aortic ligation and gradually recovered following resumption of flow. Motor and sensory evoked potentials behaved similarly to high aortic ligation. PMID- 2218847 TI - Cerebral cysticercosis. AB - We studied 143 cases of cerebral cysticercosis over a 30-year period. In 46 there was hydrocephalus due to cysts obstructing the cerebrospinal fluid pathways, with signs of hydrocephalus and cerebellar dysfunction. In 97 there were cysts in the cerebral parenchyma, causing symptoms of intracranial hypertension alone in 22 cases, with additional neurological deficits in the remainder. Before 1980 diagnosis was made by pneumoencephalography and ventriculography, but since then it has mostly been done by computed tomography. In 28 cases scanned, typical abnormalities were present in 25. Complement fixation tests were positive in serum in 74% of cases and in cerebrospinal fluid in 73%, and the enzyme-linked immunosorbent assay test was positive in serum in 90% and in cerebrospinal fluid in 92%. Treatment of cases with hydrocephalus was by removal of the cysts at craniotomy, with placement of a shunt where necessary. Intracranial hypertension caused by parenchymal cysts was treated with steroids and osmotic agents, if possible. In resistant cases subtemporal decompression was needed, unilateral in 55 cases and bilateral in eight. Mortality in the acute stage was 11%, with a further 20% at follow up. PMID- 2218848 TI - Experimental isobaric subarachnoid hemorrhage: regional mitochondrial function during the acute and late phase. AB - Patients treated for aneurysmal subarachnoid hemorrhage show, in the long-term follow up, an elevated rate of cognitive disturbances that are mainly related to the impact of the initial bleeding: the neurotoxic effects of blood deposition in subarachnoidal spaces may result in a diffuse encephalopathy, but the intrinsic mechanism and the biochemical correlates are not known. In the present study we have evaluated mitochondrial function after experimental induction of subarachnoid hemorrhage. Mitochondrial function was evaluated in four different rat brain areas (frontal cortex, occipital cortex, hippocampus, and brain stem) after experimental isobaric subarachnoid hemorrhage in rats. Subarachnoid hemorrhage was induced by injecting 0.07 mL of arterial autologous blood into the cisterna magna. Intracranial pressure did not significantly increase. The nonsynaptic mitochondrial fraction was isolated from different rat brain areas, and the maximal rate of enzymatic reactions of some key enzymatic activities related to the Krebs cycle [nicotinamide adenine dinucleotide (oxidized form) (NAD+)-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase] and of the electron transfer chain (cytochrome oxidase) were evaluated. The nonsynaptic mitochondrial fraction was utilized also to check parameters related to the mitochondrial respiration: state 3, state 4, uncoupled state, respiratory control ratio, and adenosine 5'-diphosphate/oxygen ratio. The biochemical parameters were measured at 1 and 72 hours after the subarachnoidal injection of blood. Subarachnoid hemorrhage did not affect the mitochondrial enzymatic activities both at 1 and 72 hours, while the mitochondrial enzymatic activities parameters were significantly affected: in particular, a significant decrease of respiratory control ratio in all tested brain areas was demonstrated. The increased mitochondrial vulnerability in the delayed phases could be one of the biochemical correlates of post-hemorrhagic encephalopathy. PMID- 2218849 TI - Effects of medical and surgical treatment on cerebral perfusion and cognition in patients with chronic cerebral ischemia. AB - The effects of medical treatment with and without cerebral revascularization procedures on cognition and cerebral blood flow were compared among 36 patients with extracranial occlusive cerebrovascular disease and cognitive impairments. Three comparable groups were studied. The first group (N = 18) received only medical treatment by control of risk factors for stroke (including hypertension, diabetes, and hyperlipidemia) and antiplatelet aggregant medication. The second group (N = 10) had the same medical treatment plus superficial temporal-to-middle cerebral artery bypass, and the third group had the same medical treatment plus carotid endarterectomy. Regional cerebral blood flow and cognition were monitored in all three treatment groups over a 3-year interval. All groups showed stabilization without expected rates of decline for both cerebral blood flow and cognition, but no statistically significant differences emerged among the treatment groups. PMID- 2218850 TI - Effect of diltiazem and thromboxane A2 synthetase inhibitor (OKY-046) on vessels following experimental subarachnoid hemorrhage. AB - In order to examine the functional changes in the vascular smooth muscle, the effects of a thromboxane A2 synthetase inhibitor (OKY-046) and a calcium channel blocker (diltiazem) on vessels following subarachnoid hemorrhage, and the contractile activity of cerebral vessels with various vasoactive agents, were investigated by studying isometric tension recordings in rings of cat basilar artery. The maximum contractile activities of the vessels in response to noradrenalin and adrenaline during the course of subarachnoid hemorrhage were significantly less than those in the control group. On the other hand, the maximum contractile activity of the vessels in response to prostaglandin F2 alpha on the seventh day following subarachnoid hemorrhage was significantly augmented compared with that in the control group. A significant decline in the relaxation of responsiveness to diltiazem during the course of subarachnoid hemorrhage was observed compared with that of diltiazem in the control group. This responsiveness to vasoactive agents was not influenced by the application of OKY 046. The present study reveals functional changes in vascular smooth muscle exposed to subarachnoid hemorrhage in response to vasoactive agents and a calcium entry blocker. Thromboxane A2 may not be a significantly influential factor in the present results. It is suggested that cerebral vasospasm may well be related to functional changes of the arterial wall, which appear to be associated with derangement of the mechanisms of smooth muscle constriction and dilatation based on organic changes. PMID- 2218851 TI - Intractable complex partial seizures associated with occult temporal lobe encephalocele and meningoangiomatosis: a case report. AB - Occult congenital temporal lobe encephalocele has rarely been reported in association with medically intractable complex partial seizures. The four previously reported cases were unsuspected preoperatively. We present the case of an 18-year-old woman with intractable complex partial seizures since age 13. Seizure onset was electrically localized to the right temporal lobe. Preoperative neuroimaging studies revealed a middle fossa defect and inferior herniation of the right temporal lobe. Pathologic examination of the resected encephalocele revealed prominent features of meningoangiomatosis. We believe this to be the first case of temporal lobe encephalocele and epilepsy to be diagnosed preoperatively, and the first case also to be associated with meningoangiomatosis. The relevant literature on meningoangiomatosis and on temporal lobe encephalocele as a cause of epilepsy is reviewed. PMID- 2218852 TI - An unusual epidural, vascular spinal lipoma in a 3-year-old child: a case report and review of the literature. AB - Epidural lipomas are usually benign tumors affecting the spinal cord. We report the unusual presentation of a cervicothoracic spinal lipoma associated with a cervical dysraphism in a young boy. Diagnostic options using magnetic resonance imaging and gadolinium-diethylenetriaminepentaacetic acid are discussed as a pathway to early diagnosis of these and other occult spinal lesions. PMID- 2218853 TI - Total removal of an arteriovenous malformation embedded in the brain stem. AB - The removal of brain stem arteriovenous malformations is one of the most challenging problems in neurosurgery. The authors report a successful total removal of an arteriovenous malformation situated in the middle cerebellar peduncle, which was embedded in the floor of the fourth ventricle. The importance of dissection "flush" with coils of an arteriovenous malformation is stressed. PMID- 2218854 TI - Cavernous-carotid thrombosis and ocular motor paresis. AB - A 64-year-old man presented with the acute onset of unilateral blindness and ipsilateral ocular motor paresis. Occlusion of the central retinal artery associated with thrombosis of the internal carotid artery in the cavernous sinus was demonstrated by angiography and magnetic resonance imaging. Cases of carotid thrombosis associated with ipsilateral ocular motor paresis are rare. The pathophysiology of intracavernous carotid thrombosis is discussed in connection with blood supply of the cranial nerves in the cavernous sinus. PMID- 2218855 TI - Neonatal intracranial teratomas. AB - Two neonates with intracranial teratomas presented with cranial enlargements a few weeks after birth. Both cases underwent surgery: one died intraoperatively; the other is the longest known survivor, alive 7 years and 9 months after subtotal excision of a mature teratoma of the left sylvian fissure. Previous operations have been relatively few and nearly all have been unsuccessful. Size and favorable location may be the most important prognostic features regardless of the histologic classification as mature or immature. One of our cases demonstrates that even subtotal excision of a mature teratoma can result in long term survival. PMID- 2218856 TI - Value of magnetic resonance imaging in spontaneous extradural spinal hematoma due to vascular malformation: case report. AB - A case of spinal cord compression due to spontaneous extradural spinal hematoma is reported. A spinal arteriovenous malformation was suspected on the basis of magnetic resonance imaging. Early surgical exploration allowed a complete neurological recovery. The vascular malformation was histopathologically confirmed. The role of magnetic resonance imaging in the evaluation of acute spinal cord compression syndromes is stressed. PMID- 2218857 TI - Spinal extradural cavernous hemangioma. AB - Three cases of isolated spinal extradural cavernous hemangiomas are reported, two in the thoracic and one in the lumbar region. One of them manifested as acute cord compression, the other two as chronic progressive myelopathy or radiculopathy. A total excision or subtotal excision with irradiation was performed. All of them had good functional recovery. The clinical picture, radiological diagnosis, and optimal method of treatment are discussed. The relevant literature is reviewed. PMID- 2218858 TI - International perspective: neurological surgery in Nicaragua. PMID- 2218859 TI - Two surgically cured cases of sub-ependymoma with emphasis on magnetic resonance imaging. PMID- 2218860 TI - [The results of simultaneous radio-chemotherapy in advanced head and neck tumors]. AB - Patients suffering from locally advanced squamous cell carcinoma of the head and neck were treated with three courses of simultaneous radio-chemotherapy. Chemotherapy consisted of cis-platinum, 60 mg/m2 i.v. on day 2; 5-FU, 350 mg/m2 i.v. bolus on day 2; leucovorin calcium, 50 mg/m2 i.v. on day 2; 5-FU, 350 mg/m2/24 hrs continuously infused over 96 hrs from day 2 to day 5 and leucovorin calcium, 100 mg/m2/24 hrs continuously infused over 96 hours from day 2 to day 5 each course. Radiotherapy was administered from day 3 to day 11. 23.4 Gy were given in 13 fractions, twice a day with a minimum interval of four hours. This schedule was repeated on days 22 and 44. The total radiation dose amounted to 70.2 Gy/51 days. From 1984 to 1986, 62 patients were entered in this prospective trial. Three patients deceased due to massive hemorrhage during therapy, one patient was not eligible due to a second malignancy. 5/58 evaluable patients had a UICC-Stage III cancer, 53/58 had a UICC-Stage IV cancer. 48/58 (81%) showed a clinically complete response to therapy, 10/58 (17%) achieved partial response three months after the end of treatment. In 16/58 patients loco-regional cancer was not controlled (minimum follow-up 2 years), in 12/58 distant metastases occurred. Loco-regional control rate is estimated at 66% +/- 7% (Kaplan Maier). PMID- 2218861 TI - A simple experimental technique for interstitial iridium-192 high dose-rate afterloading. AB - A simple experimental technique for interstitial iridium-192 high dose-rate afterloading is described which allows to perform experimental brachytherapy on a rat tumor model. To illustrate the possibilities and limitations of the technique, rhabdomyosarcoma R1H of the rat were subjected to a combined brachy- and teletherapy treatment applying a total dose of 60 Gy in fractions of 2 Gy. The results show that the surgical procedure had no influence on tumor response. However, would healing was considerably disturbed in animals which received afterloading treatment. PMID- 2218862 TI - Optimized afterloading therapy of cervix carcinoma with the discontinuous movement of the iridium source. AB - Optimization of brachytherapy means first of all a physical adaptation of isodoses to shape and tolerances of radiosensitive tissues surrounding the target volume, and also to shape and dosage requirements of the tumor to be treated. Dose computation algorithms for optimizing afterloading therapy postulate the discontinuous movement of the iridium source. A new method for the application of the discontinuous movement to our afterloading equipment was worked out. It combines the abilities of the source movements and the demands of the clinical optimization of the isodoses used for the brachytherapy of cervix carcinoma. PMID- 2218864 TI - [Aspects of the computer-assisted irradiation planning for the HDR (high dose rate) afterloading technique]. AB - A mathematical optimization method will be discussed concerning the three dimensional radiation treatment planning of the HDR-afterloading technique. Program libraries of the EDV Center of the University of Essen were used. PMID- 2218863 TI - [A low-cost localization technique for high-dose-rate afterloading applicators]. AB - For radiation safety control radiotherapy today needs a method to check the correct position of a HDR-gynecological applicator before afterloading treatment. At the university clinic in Essen, West Germany, a surgical c-X-ray plant was used for the construction of an orthogonal X-ray-photograph plant, which combines illumination and photographs as localisation technique. PMID- 2218866 TI - An energy monitor for electron accelerators. AB - A monitor useful for checks of the energy selector scale of medical electron accelerators was developed and tested. It consists of a linear array of flat ionization chambers sandwiched between absorber plates of low-Z material. The first chamber at the electron beam entrance may be used to produce a reference signal Sr, if not another suitable reference signal is taken. The following chambers are electrically connected and deliver the measuring signal Sm. A clinical dosimeter can be used for recording current or charge. The energy dependent electron range parameters Rp, R50 and R80 in water vary as linear functions of the ratio Sm/Sr. The best linear fit was obtained for the half value layer R50. Three types of the energy monitor are described, and experimental results obtained with a linear accelerator and a betatron between 5 and 25 MeV are reported. Uncertainties for checks of R50 with a calibrated energy monitor were not larger than 1 to 2 mm. Theoretical considerations by a computer model support these results. PMID- 2218865 TI - [Dose calculation for very small irregular electron beam fields. 1. Dose calculation for the central beam using a simple field zone method]. AB - Very small electron beams show considerable reduction of the dose output factor, the therapeutically relevant range, the practical range and the therapeutically relevant field size, compared to broad beams. The first three effects were measured on the central beam axis for different quadratic field sizes and are presented in the first part of this publication. A simple field zone method for calculation of irregular shaped electron beams was developed from the different depth dose curves. The method allows the determination of the maximum dose and the 80% range with sufficient accuracy for practical purposes. The examination of the reduction of the therapeutically relevant field size and the consequences following thereof with respect to the adequate electron therapy of a small irregular target volume will be published in a second part. PMID- 2218867 TI - Comparison of micronucleus frequencies and proliferation kinetics in three X irradiated cell lines. AB - The kinetics of the occurrence of micronuclei was correlated with the survival of three mammalian cell lines of human, monkey, and mouse origin after irradiation with 240 kV X-rays. Particular attention was paid to the evaluation of the individual proliferation kinetics of the cell lines as well as to the characterization of micronuclei subpopulation with respect to size and possible biological importance using DNA and BUdR labelling techniques, fluorescence microscopy, and image analysis. The results demonstrate very characteristic size distributions of micronuclei for the three cell lines independent of radiation dose and time after irradiation. A close correlation between cell death and the occurrence of micronuclei (expressed as a calculated "MN index") after irradiation could be established only when the kinetics of progression of cells through the cell cycle (e.g. the doubling time) and the biological characteristics of micronuclei (e.g. BUdR positivity, the micronucleus frequencies, and the number of micronuclei per main nucleus) were taken into account. Therefore, the micronucleus assay might not be useful as a quantitative predictive assay in vivo but may allow qualitative estimations of radiation damage only because the necessary proliferation parameters of the cells might not be possible to establish in vivo. PMID- 2218868 TI - [The effect of adriamycin derivatives in combination with x-rays on MeWo and Be11 cells]. AB - The survival rate of human melanoma cells after X-ray irradiation, treatment with adriamycin derivatives and combined treatment with X-rays and adriamycin derivatives was measured by means of the colony formation test. After X-ray irradiation the melanoma cells showed a high resistance for cell survival. In all tests the Be11-cells were more resistant than MeWo-cells. On combined exposure especially with higher doses of adriamycin derivatives, both cell lines showed the interesting effect, that with increasing concentration the survival rate decreased whereas the D(o) increased. Aclacinomycin-A (ACM-A) and Pirarubicin reduced recovery processes after X-ray irradiation. Therefore Be11-cells showed a four times higher DMF (dosis modifying factor) after ACM-A-treatment than MeWo cells. Low ACM-A-concentrations combined with low X-ray doses showed on both cell lines supraadditive effects. The effect of pirarubicin was in most of the tests only additive. Compared with ACM-A, pirarubicin was less cytotoxic, showed a larger therapeutic range, caused a smaller D(o) and Dq and had a supraadditive effect in low concentrations on both cell lines. For clinical combined therapy with patients ACM-A is probably better suited than pirarubicin. PMID- 2218869 TI - The challenge of a new decade--a surgeon's perspective of the 1990s. PMID- 2218870 TI - Prospective evaluation of clinical and pathologic detection of axillary metastases in patients with carcinoma of the breast. AB - Complete axillary dissection was performed in 287 patients undergoing modified radical mastectomy between 1984 and 1987 to identify patterns of axillary node metastases, as well as discontinuous axillary node ("skip") metastases. Positive pathologic findings were compared with preoperative clinical examinations in 266 patients and showed only 60 cases (22.6%) clinically suspicious for tumor, in contrast to 131 (45.6%) with pathologically confirmed positive lymph nodes. Axillary contents were classified level I, II, or III based on their relationship to the pectoralis minor muscle. An average of 24.2 nodes was resected per patient (level I, 10; level II, 8.1; and level III, 5.3). Tumors ranged in size from 0.5 to 12.0 cm (mean, 2.6 cm), and increasing tumor size was associated with an increased likelihood of positive nodes. The data on 204 patients with complete clinical and pathologic data show that of 119 patients with negative level I nodes a limited axillary dissection (level I only) would fail to identify 6 with positive level II and 2 with positive level III nodes, whereas of 85 patients with positive level I nodes limited axillary dissection would fail to identify 17 with positive level II nodes, 7 with positive level III nodes, and 27 with positive levels II and III nodes. Complete axillary dissection (levels I, II, and III) should be performed to stage patients accurately, as well as to remove tumor involved nodes and diminish local axillary recurrences. Clinical examination of the axilla appears to be a poor means of identifying axillary metastatic cancer. PMID- 2218871 TI - Short-term tamoxifen plus chemotherapy: superior results in node-positive breast cancer. AB - Three hundred eleven patients with node-positive breast cancer were randomized to one of three adjuvant treatments: cyclophosphamide (Cytoxan), methotrexate, and 5 fluorouracil; all of the above with tamoxifen citrate; or all of the above with tamoxifen and bacillus Calmette-Guerin vaccination. Local therapy for all patients was a modified radical mastectomy. Estrogen receptors were measured on all primary tumors. Patients were stratified by the number of positive nodes (one to three nodes and more than three nodes) and estrogen-receptor value (less than 3 femtomole/mg and greater than or equal to 3 femtomole/mg). Follow-up is available, with a mean of 9.1 and maximum of 14.2 years. In this study the efficacy of short-term tamoxifen is apparent over that of chemoimmunotherapy alone and continues to be significant with prolonged follow-up. The addition of tamoxifen to chemoimmunotherapy significantly prolonged disease-free survival among patients with estrogen receptor-positive tumors who were postmenopausal, who had larger tumors (greater than 3 cm), or who had more extensive axillary node involvement (more than three nodes). Tamoxifen improved overall survival for patients with estrogen receptor-positive tumors larger than 3 cm. The addition of bacillus Calmette-Guerin Cytoxan, methotrexate, 5-fluorouracil, and tamoxifen did not significantly alter disease-free or overall survival. PMID- 2218872 TI - Ascending cholangitis: surgery versus endoscopic or percutaneous drainage. AB - A retrospective review of 61 patients with calculous cholangitis was carried out. There were 31 men and 30 women and their mean age was 75.8 years. All patients had abdominal pain, 87% had chills and fever, 65% had clinical jaundice, 23% were in shock, and 54% had positive blood cultures. Because intravenous hydration and antibiotics did not help, 33 patients underwent surgery, 25 patients underwent endoscopic papillotomy (EP), and three patients underwent percutaneous transhepatic drainage of the common bile duct (PTD). Morbidity in the surgery group included two wound infections, one respiratory failure, and one renal failure. Morbidity in the EP-PTD group was one case of arterial bleeding requiring surgery and one of pancreatitis treated conservatively. Two patients (6%) died in the surgery group, one of sepsis and the other of cardiorespiratory arrest. In the EP-PTD group nine patients (32%) died of sepsis and multisystem organ failure. These patients were considered too ill to undergo surgery and thus repeat EP-PTD was carried out. Cholangitis persisted, and retained common bile duct stones with sepsis was the cause of death. Thus when initial EP or PTD is unsuccessful, surgical exploration of the common bile duct should be carried out to control sepsis. PMID- 2218873 TI - Are cystgastrostomy and cystjejunostomy equivalent operations for pancreatic pseudocysts? AB - To compare the effectiveness of cystgastrostomy and cystjejunostomy for treatment of pancreatic pseudocysts, 39 patients with cystgastrostomy were compared to 59 patients with cystjejunostomy. The groups were comparable in age, sex, cause of pancreatitis, pseudocyst location, symptoms, and preoperative serum amylase level. Cysts treated with cystgastrostomy were larger (mean diameter, 11.1 +/- 0.9 cm) than cysts treated by cystjejunostomy (mean diameter, 6.7 +/- 0.7 cm) (p less than 0.05). Mean duration of surgery was 148 +/- 11 minutes for cystgastrostomy versus 265 +/- 15 minutes for cystjejunostomy (p less than 0.05). Mean blood loss was 397 +/- 82 ml for cystgastrostomy versus 703 +/- 80 ml for cystjejunostomy (p less than 0.05) Mean intraoperative fluid requirements were 2640 +/- 313 ml for cystgastrostomy and 4403 +/- 362 ml for cystjejunostomy (p less than 0.05). Cyst recurrence was 10% for cystgastrostomy versus 7% for cystgastrostomy. Postoperative gastrointestinal bleeding occurred in 8% of patients with cystgastrostomy and in 2% of patients with cystjejunostomy. Infection problems with cystjejunostomy included two wound infections and one case of septicemia; infection problems with cystjejunostomy included five intraabdominal abscesses, two wound infections, and one case of pneumonia. Two patients died with cystgastrostomy (both from gastrointestinal bleeding); two patients died with cystjejunostomy (one from intraabdominal sepsis and one from pulmonary embolus). Cystgastrostomy was used for significantly larger pseudocysts and was associated with significantly less blood loss and operating time than cystjejunostomy (p less than 0.05). Morbidity and mortality from cystgastrostomy and cystjejunostomy were comparable, although gastrointestinal bleeding was more common with cystgastrostomy and intraabdominal abscess was more common with cystjejunostomy. Since cystgastrostomy can usually be performed more quickly and with less blood loss, it should be considered whenever anatomically feasible. PMID- 2218874 TI - Pancreatogastrostomy: a safe drainage procedure after pancreatoduodenectomy. AB - The purpose of this study was to evaluate the role of pancreaticogastrostomy as an alternative method of restoring pancreaticointestinal continuity after pancreaticoduodenectomy. Since 1975, 45 patients have undergone pancreaticogastrostomy after pancreaticoduodenectomy at our institution. Pancreaticoduodenectomy was performed for pancreatic carcinoma (24 patients), ampullary carcinoma (8 patients), duodenal carcinoma (4 patients), common bile duct carcinoma (4 patients), pancreatic islet cell carcinoma (1 patient), trauma (1 patient), extensive colon carcinoma (1 patient), chronic pancreatitis (1 patient), and gastroduodenal artery aneurysm (1 patient). There was one operative death, for an overall operative mortality rate of 2%, and seven patients had major postoperative complications, for an overall morbidity rate of 15%. No pancreatic anastomotic leaks or other complications related to the pancreaticogastrostomy occurred. Twenty-four patients have died of recurrent carcinoma, with a mean survival of 25 months (range, 5 to 66 months), and 20 patients are alive and well, with a mean follow-up of 27 months (range, 2 to 106 months). Eight of these patients are alive 2 or more years after operation and four do not have exocrine pancreatic insufficiency. This experience confirms that pancreaticogastrostomy is a safe method of pancreatic drainage after pancreaticoduodenectomy and suggests that it may have technical advantages and therefore merits more widespread application. PMID- 2218875 TI - Early results of combined electrohydraulic shock-wave lithotripsy and oral litholytic therapy of gallbladder stones at the University of Iowa. AB - One hundred thirty-three patients were entered into a randomized, double-blind, placebo-controlled trial of extracorporeal shock-wave lithotripsy for symptomatic gallstones versus extracorporeal shock-wave lithotripsy plus adjuvant litholytic therapy with ursodeoxycholic acid (UDCA). Six months after lithotripsy, patients receiving placebo were crossed over to UDCA therapy without unblinding the study. One hundred sixteen patients have completed 6 months of follow-up. Five patients were dropped from the study. Nine percent have required cholecystectomy (11 patients with biliary colic and 1 with acute cholecystitis). Ninety-one patients had a solitary stone (64 patients had stones less than or equal to 20 mm and 27 patients had stones greater than 20 mm in diameter), and 25 patients had two to three stones. Fifty percent were retreated. Cumulative stone-free rates at 6, 12, and 18 months were 26%, 39%, and 41%, respectively. At 6 months there was a significant advantage for patients treated with UDCA versus placebo (36% vs 17% were stone free) that had disappeared by 12 months (placebo-treated patients had received 6 months of UDCA). Patients with solitary stones equal to or less than 20 mm in diameter treated with UDCA had stone-free rates at 6, 12, and 18 months of 58%, 58%, and 62%, respectively, versus 27%, 56%, and 50%. The difference was significant only at the 6- month follow-up. Stone-free rates for patients with large solitary stones and multiple stones were very low. Extracorporeal shock wave lithotripsy is both safe and effective therapy for treatment of symptomatic gallstones in patients with a solitary stone equal to or less than 20 mm in diameter. UDCA markedly improves the efficiency of the procedure and results in a stone-free gallbladder sooner. PMID- 2218876 TI - Early tracheostomy for primary airway management in the surgical critical care setting. AB - During a 12-month period, 264 patients with multiple injuries who required mechanical ventilation were admitted to the surgical intensive care unit. One hundred twenty patients (46%) were disengaged from the ventilator, and 38 patients (14%) died. Of the remaining 106 patients (40%) 51 patients (group I) were to receive tracheostomy within 1 to 7 days, and 55 patients (group II) underwent late (8 or more days after admission) tracheostomy. Multiple variables in four categories (admission, operative, ventilatory, and outcome) were analyzed prospectively to define the impact that early tracheostomy had on duration of mechanical ventilation, intensive care stay, and hospital stay. Morbidity and mortality rates of the procedures were assessed. Early tracheostomy, in a homogeneous group of critically ill patients, is associated with a significant decrease in duration of mechanical ventilation, as well as shorter intensive care unit and hospital stays, compared with translaryngeal endotracheal intubation. There were no deaths attributable to tracheostomy, and overall morbidity of the procedures was 4%. We conclude that early tracheostomy has an overall risk equivalent to that of endotracheal intubation. Furthermore, early tracheostomy shortens days on the ventilator and intensive care unit and hospital days and should be considered for patients in the intensive care unit at risk for more than 7 days of intubation. PMID- 2218877 TI - Combined orthopedic and vascular injury in the lower extremities: indications for amputation. AB - A retrospective review was undertaken to determine risk factors associated with amputation after open fractures of the lower extremity that were complicated by vascular injury. During an 11-year period ending in December 1987, we observed open fractures in 31 patients and injuries to the popliteal artery in 16 patients, to the tibial arteries in eight patients, to the femoral artery in five patients, and to the dorsal artery of the foot in two patients. Vascular repair was accomplished in 25 patients; 12 patients had primary end-to-end anastomosis, 12 patients had reverse saphenous vein grafts, and one patient had a bovine graft. Of these 25 patients, five patients required amputation because of infection and three patients required amputation because of continued ischemia. Three patients with irreparable damage had immediate amputation, and three patients without distal ischemia had vessel ligation only. The risk factors associated with amputation were shock on admission (10 of 19 patients [p less than 0.02]) and a crushed extremity (10 of 18 patients [p less than 0.01]). The overall amputation rate, which included three immediate amputations and eight late amputations, was 35.2%. The data suggest that limb salvage is possible in two thirds of patients with combined orthopedic and vascular injuries of the lower extremity, but a history of shock or crush injury with vascular compromise is an unfavorable prognostic sign. PMID- 2218878 TI - Inadequate granulopoiesis after major torso trauma: a hematopoietic regulatory paradox. AB - Late postinjury sepsis is largely the result of defective host defense including failure to maintain an adequate number of functioning phagocytic cells. In this study we used stem cell culture techniques to measure colony-stimulating activity and have quantitated the number of circulating myeloid stem cells to see if defects in granulopoiesis occur after major torso trauma. Forty-two acutely injured patients (13 blunt and 29 penetrating injuries; mean age, 29.7 years) undergoing laparotomy with an abdominal trauma index of 15 to 40 were studied prospectively. Blood samples were obtained on days 1, 5, and 10. Patients were segregated by injury severity: abdominal trauma index less than 25 (n = 25) versus abdominal trauma index greater than or equal to 25 (n = 17). The more severely injured (abdominal trauma index greater than or equal to 25) patients had fewer circulating granulocytes and monocytes. Colony-stimulating activity was below normal control levels in all patients and was decreased further with increased injury severity. The more severely injured patients had a blunted bone marrow response (significantly fewer circulating myeloid stem cells) and suffered more major septic complications (24% vs 8%). In conclusion, major trauma to the torso causes a paradoxic depression in granulopoiesis that worsens with increased injury severity and may contribute to late septic morbidity. This colony stimulating activity deficiency state is similar to that seen after major burns and may be amenable to future modulation. PMID- 2218879 TI - Subxiphoid pericardiotomy versus echocardiography: a prospective evaluation of the diagnosis of occult penetrating cardiac injury. AB - Diagnostic subxiphoid pericardiotomy (SP) is presently advocated for the diagnosis of occult cardiac injuries in patients with stable vital signs with juxta-cardiac-penetrating chest wounds. This approach, however, results in a reported 80% negative pericardial exploration rate. To investigate the reliability of bedside two-dimension echocardiography (2-D echo) in predicting cardiac injury as compared to SP, a prospective study was undertaken of patients with stable vital signs who were admitted with penetrating chest wounds that were located within the space bounded by the manubrium, nipples, and subcostal line. Initial evaluation of the patients with bedside 2-D echo was found to have a 96% accuracy, 97% specificity, and 90% sensitivity in predicting cardiac injury. The only false-negative findings were in a patient who consented to SP 18 hours after bedside 2-D echo was performed. The reliability of bedside 2-D echo compared to SP was not significantly different according to the kappa measure of reliability. These data suggest that bedside 2-D echo is an expeditious and reliable method to diagnose occult cardiac injuries during the initial assessment of a patient with stable vital signs who had penetrating chest trauma. This approach may allow for the selective use of SP on patients with positive bedside 2-D echo and could eliminate unnecessary surgical procedures. PMID- 2218880 TI - The use of the Jarvik-7 total artificial heart and the Symbion ventricular assist device as a bridge to transplantation. AB - The proliferation of transplantation programs has not been paralleled by a similar increase in the availability of organ donors. Between 1984 and 1987, 104 orthotopic heart transplantations were performed at Loyola University Medical Center. During the same period, 25 patients died while awaiting a donor organ. To reduce the mortality, we began using the total artificial heart (TAH) and a ventricular assist device (VAD) as a bridge to transplantation in 1988. Of 29 patients who underwent transplantation, 15 patients required a TAH and three patients required a VAD as a bridge. The underlying heart conditions were ischemic cardiomyopathy (11 patients), dilated cardiomyopathy (5 patients), giant cell myocarditis (1 patient), and allograft failure (1 patient). The average duration of mechanical support was 10 days (range, 1 to 35 days). Of the 17 patients who successfully underwent transplantation, 1 patient died at 17 days because of acute rejection of the transplanted heart, and another patient died at 14 days because of a cerebral vascular event. Fifteen patients (83%) were long term survivors. Nine patients required reoperation for bleeding. While the mechanical device was in place, the activated clotting time was maintained between 170 and 200 seconds with heparin. Dipyridamole was given. We conclude that the TAH and VAD are excellent mechanical bridges to transplantation. PMID- 2218881 TI - Heparin-induced thrombocytopenia in patients who undergo open heart surgery. AB - To determine whether heparin-dependent antiplatelet antibodies (HAAb) have an effect on morbidity and/or mortality rates, we reviewed the cases of 3438 patients who underwent open heart surgery from 1981 to 1989. Forty-six patients (1.3%) had HAAb. The patients were divided into two groups: those patients who were known to have HAAb before surgery (group I) and those patients who were diagnosed with HAAb after surgery (group II). Group I patients (n = 5) were pretreated with platelet-inhibiting drugs before reexposure to heparin during cardiopulmonary bypass and were maintained with strict abstinence from heparin afterward. Their lowest observed platelet counts ranged from 42,000/mm3 to 89,000/mm3 (median, 63,00/mm3). Thromboembolic complications did not occur, and all patients survived. Group II patients (n = 41) who were diagnosed to have HAAb after surgery had not been pretreated with platelet-inhibiting drugs before surgery. Lowest platelet counts ranged from 11,000/mm3 to 128,000/mm3 (median, 42,000/mm3). Bleeding complications occurred in 21 patients (51%), and thromboembolic complications occurred in 13 patients (32%). Hospital mortality in group II patients was 37%. Late recognition of HAAb was associated with an increase in morbidity and mortality rates. Thromboembolic complications of HAAb, which had been diagnosed before surgery, were eliminated, and bleeding was reduced by pretreatment with platelet-inhibiting drugs and strict abstinence from heparin after surgery. PMID- 2218882 TI - Is DNA ploidy of prognostic significance in stage I cutaneous melanoma? AB - Recent studies have suggested that the presence of DNA aneuploidy in stage I cutaneous melanoma carries a poor prognosis. To see if our experience correlated with these reports, we used DNA analysis by flow cytometry of propidium iodide stained nuclei disaggregated from formalin-fixed paraffin-embedded tissue of biopsy specimens to retrospectively study 55 patients who had cutaneous stage I melanomas. The patients had been treated from 1977 to 1987 with a mean follow-up of 5.4 years. Thirty-nine (71%) of the 55 histograms were diploid, and 16 (29%) of the histograms were aneuploid. DNA content was significantly associated with other conventional prognostic factors, including growth pattern, ulceration, pathologic stage, tumor thickness, and Clark's level. DNA aneuploidy was significantly related to disease-free survival and predicted a poorer prognosis (p less than 0.05), but when stratified for tumor thickness it lost significance. A multivariate discriminant function analysis of 12 factors in melanoma showed six factors to be independently significant in determining prognosis. DNA content (p = 0.034) ranked fifth in importance behind growth pattern (p less than 0.001), ulceration (p less than 0.001), thickness (p = 0.001), and pathologic stage (p less than 0.005). DNA content, although significantly associated with conventional prognostic factors and disease-free survival, is not the best indicator of biologic behavior of melanomas in this study. Further investigation into its usefulness is necessary before DNA content can become a routine diagnostic modality in the work-up of stage I cutaneous melanomas. PMID- 2218883 TI - Anomalies of intestinal rotation in childhood: analysis of 447 cases. AB - This report concerns 447 infants and children with anomalies of rotation and fixation. Patients were placed in four groups based on initial symptoms. Group A involved 18 patients with acute midgut volvulus. At laparotomy, midgut volvulus was noted and reduction of midgut volvulus and a Ladd procedure were performed in 10 cases and resection was required in 8. There were five deaths (28%). Group B included 54 children with chronic symptoms of intermittent volvulus or duodenal obstruction. Group C involved 44 cases of malrotation observed during exploration for other disorders. Patients in groups B and C underwent a Ladd procedure and appendectomy. There were five unrelated deaths. Group D included 331 neonates with malrotation caused by either diaphragmatic hernia (n = 111) or abdominal wall defects (n = 220). A Ladd procedure was performed on 48 patients with abdominal wall defects and 29 surviving children with diaphragmatic hernia. Only 2 of 172 (1.2%) patients with abdominal wall defects and 1 of 34 (2.9%) patients with diaphragmatic hernia not treated for malrotation had midgut volvulus. Midgut volvulus is more common in infants and is associated with a high mortality rate (28%). Patients with malrotation and chronic obstructive symptoms or those observed during other elective procedures should undergo a Ladd procedure because of the risk of midgut volvulus. The risk of midgut volvulus is low in patients with abdominal wall defects and, probably as a result of adhesions from previous neonatal operations. PMID- 2218884 TI - Long-term follow-up of the ileoanal anastomosis in children and young adults. AB - The purpose of this study was to carry out a long-term study of the ileoanal anastomosis (IAA) in children and young adults, comparing the straight IAA to the J pouch. One hundred twenty-one young people who had undergone IAA were studied, with 114 available for long-term follow-up. One hundred one were 18 years and under. Forty-nine patients had a straight IAA and 72 had a J-pouch reservoir. There were no deaths. After surgery, three children had intraabdominal sepsis and one had pelvic sepsis, but it did not lead to excision of the IAA. The mean stool frequency in all 114 patients was 5.0 +/- 2.5 per day and 1.2 +/- 1.1 at night. The mean number of stools for the straight IAA was 6 per day and 2.1 at night. The mean number of stools for the straight IAA with balloon dilations was 5.8 per day and 1.2 at night, and for the J pouch it was 4 per day and 1 at night. Patients with both the J pouch and straight IAA had good to excellent sensation, with patients with the J pouch always able to distinguish flatus from stool in 87% of patients and almost always in 13%. Daytime continence was very good in both groups. Moderate nighttime loss of stool occurred in 10 patients, 6 with a straight IAA and 4 with a J pouch. Ninety-five percent of the 114 patients were satisfied or very satisfied, with most children with a J pouch very satisfied. The J pouch remains the procedure of choice in young people. PMID- 2218885 TI - Kidney transplantation in patients aged sixty years and older. AB - Outcomes of renal transplantation were reviewed for 26 transplants performed in 25 patients 60 years of age or older between 1985 and 1989. Three grafts were from family donors and 23 were from cadaver donors. Twenty-one were first transplants and five were retransplants. Cyclosporine was used as primary immunosuppression and azathioprine and prednisone were administered to most patients. Overall patient and graft actuarial survival rates were 79% and 71%, respectively, at both 1 and 3 years. Patients (n = 14) free of both diabetes and cardiac disease (low risk) had 1- and 3-year patient and graft survival rates of 91% and 84%, respectively. Conversely, high-risk patients (n = 12) had patient and graft survival rates at 1 and 3 years of 67% and 58%, respectively. Early deaths (less than or equal to 6 months) were caused by sepsis (two patients) or cardiac events (three patients), and four of the five were in high-risk patients. Irreversible rejections and serious infectious complications were not as common as steroid-induced diabetes, which occurred in five patients. This experience suggests that kidney transplantation can be done safely and successfully in patients older than 60 years of age and should be the treatment of choice for low risk patients in this category. PMID- 2218886 TI - Beneficial effects of fetal liver tissue on fetal pancreatic transplantation. AB - Recently, composite grafts of hepatocytes and islets have been shown to improve the survival of hepatocytes. The possibility of a reciprocal effect of hepatocytes on islet function was investigated. Diabetic Lewis rats were isografted with (1) fetal pancreas and fetal liver (FP/FL), (2) fetal pancreas alone (FP), and (3) fetal pancreas and fetal spleen (FP/FS). Grafts were transplanted to the small bowel subserosa. All (6/6) FP/FL recipients were cured (glucose less than 250 mg/dl for greater than 30 days), whereas only 72% (13/18) of FP alone and 60% (3/5) of FP/FS recipients were cured. The amount of time to normoglycemia for FP/FS recipients was less (26 +/- 15 days) compared with FP (50 +/- 29 days) or FP/FS recipients (71 +/- 40 days). Mean glucose levels at 6 weeks were 166 +/- 78 mg/dl, 237 +/- 97 mg/dl, and 355 +/- 81 mg/dl in cured FP/FL, FP, and FP/FS recipients, respectively. Glucose tolerance test results were not significantly different from those of nondiabetic control rats. In contrast to FP alone, FP/FL recipients had well-granulated hyperplastic islets and hepatocytes on histologic examination. When new isograft recipients were treated with cyclosporine, all FP recipients remained hyperglycemic; however, 75% (6/8) of FP/FL recipients were cured. In conclusion, FL in a composite graft with FP resulted in better engraftment, earlier isograft function, and protection from cyclosporine islet toxicity. PMID- 2218887 TI - Results of infrainguinal bypass for limb salvage in patients with end-stage renal disease. AB - Limb salvage in patients with end-stage renal disease (ESRD) is complicated by the diffuse, obstructive, calcific arteriopathy that makes anastomotic technique especially critical. Furthermore, decreased resistance to infection and impaired wound healing produced by host-factor deficiencies such as diabetes mellitus, hypoalbuminemia, uremia, and immunosuppression produce additional obstacles to successful limb salvage. This report summarizes our experience with distal arterial bypass procedures in these patients. A total of 32 bypass procedures were performed for limb salvage in 24 patients (17 diabetic) during a period of 5 years. The operative mortality rate was 6%. During the same period, 635 infrainguinal bypass procedures were performed by the in situ technique in patients without ESRD. Primary bypass patency was comparable in both groups at 24 months (92% vs 90%). In the group with ESRD, overall limb salvage was 83% at 2 years. Life-table analysis of bypass patency and limb salvage was thought not to be appropriate in the population with ESRD beyond 2 years because of the increased mortality rate (38%; 9/24) during this interval. It is important that limb salvage was achieved in diabetic patients with ESRD in the presence of extensive foot gangrene or ischemic ulceration. Revascularization should be considered strongly for limb salvage in all patients in this difficult population. PMID- 2218888 TI - Naloxone and spinal fluid drainage as adjuncts in the surgical treatment of thoracoabdominal and thoracic aneurysms. AB - Forty-seven patients who were treated for thoracoabdominal or thoracic aneurysms over a 5 1/2-year period were analyzed for neurologic deficit risk. Patients were divided into two groups for analysis. Twenty-four patients, who were treated from January 1984 to December 1986, did not undergo spinal fluid drainage or naloxone administration (group A). Twenty-three patients, who were treated from January 1987 to August 1989, had spinal fluid drainage (group B); 12 patients in this group also received naloxone as an intravenous drip at 1 microgram/kg/hr for 48 hours after surgery. Permanent neurologic deficits occurred in seven (29%) group A patients but in only one (4%) group B patient, who did not receive naloxone (p less than 0.03). The first two group B patients to receive naloxone showed complete reversal of neurologic deficits on waking from anesthesia. This significant reduction in neurologic deficit was associated with an increased 1 year survival rate (72% in group A, 91% in group B). We conclude that the use of naloxone and spinal fluid drainage reduces the incidence of neurologic deficit that is associated with repair of thoracoabdominal and thoracic aortic aneurysms. This reduction in neurologic deficit is associated with improved survival in the long term. The observed reversal of postoperative neurologic deficits with naloxone implicates opiates as a major factor in the pathophysiology of spinal cord ischemia. PMID- 2218889 TI - Decreased parietal cell acid secretion after vagotomy is not associated with altered gastric prostaglandin levels. AB - In a previous investigation we demonstrated that after vagotomy there is a decreased ability of parietal cells to use intracellular cyclic adenosine monophosphate (cAMP). Prostaglandins are present in gastric mucosa and have been demonstrated to be inhibitors of in vivo and in vitro acid secretion through a cAMP-mediated mechanism. In the present study we have examined in vitro acid secretion and prostaglandin E2 levels in rabbits 8 weeks after vagotomy and pyloroplasty compared with control animals to investigate the possible role of prostaglandins in postvagotomy-impaired cAMP use. In vitro acid secretion was assessed in isolated gastric glands by 14C-labeled aminopyrine uptake and prostaglandin E2-generating capacity measured by high-pressure liquid chromatography. After vagotomy, there was a decrease in basal aminopyrine uptake (p less than 0.05), as well as that simulated by histamine and 8-bromo-cAMP (p less than 0.007). No differences were observed in prostaglandin E2 levels in either gastric glands or intact fundic mucosa (p greater than 0.5). These data suggest that impaired cAMP use observed in parietal cells after vagotomy is not the result of alterations in gastric prostaglandin levels. PMID- 2218890 TI - Circadian esophageal motor function in patients with gastroesophageal reflux disease. AB - Effective esophageal peristalsis is a major determinant of esophageal clearance function and may contribute to the development of complications in gastroesophageal reflux disease. Using 24-hour ambulatory esophageal manometry, we compared the circadian esophageal motor activity of normal volunteers to that of patients with increased esophageal exposure to gastric juice and various grades of mucosal injury (no mucosal injury, esophagitis, stricture, or Barrett's esophagus). The prevalence of a mechanically defective lower esophageal sphincter, esophageal acid exposure time, and the frequency of nonperistaltic esophageal contractions during the supine, upright, and meal periods increased with increasing severity of mucosal injury. The median amplitude of esophageal contractions was compromised only in patients with a mechanically defective sphincter. This was particularly so in patients with stricture or Barrett's esophagus and was associated with an increased frequency of ineffective contractions (less than 30 mm Hg). These data show that esophageal motor function deteriorates with increasing severity of mucosal injury. This appears to be caused by persistent reflux of gastric juice across a mechanically defective lower esophageal sphincter. The need for surgical correction of a mechanically defective sphincter before the loss of esophageal body function is implicated. PMID- 2218891 TI - Long-term results of surgical resection of locally advanced colorectal carcinoma. AB - This study was undertaken to review the long-term results of multivisceral resection of locally advanced colorectal carcinoma. Between 1964 and 1980, 1042 patients underwent exploratory surgery for colorectal cancer. Of these, 58 patients (5.5%) underwent curative multivisceral resection for suspected contiguous invasion by the primary tumor. Follow-up was complete for all patients. The primary tumors were located in the rectum (38 patients), sigmoid (9 patients), left colon (6 patients), and right colon (5 patients). En bloc resection of other viscera included uterus, adnexa, bladder, vagina, small intestine, abdominal wall, liver, stomach, kidney, and ureter. The operative morbidity and mortality rates were 31% and 1.7%, respectively. Resection margins were free of tumor in 54 patients. In the four patients with tumor-positive resection margins, recurrence of disease was evident between 8 and 22 weeks after surgery (mean survival time, 8.2 months). Carcinomatous invasion of the resected contiguous organ was confirmed in 49 patients (84%). The mean survival time for patients without lymph node metastases was 100.7 months, but it was only 16.2 months (p less than 0.01) for patients with lymph node metastases. Actuarial 5 year disease-free survival rate for patients without lymph node metastases was 76% (36 of 47 patients). None of the patients (0 of 11) with lymph node metastases survived for 5 years. Three of 36 of the 5-year survivors experienced recurrence of disease before the seventh postoperative year; no cancer-related deaths occurred between 7 and 25 years. These data suggest that survival in locally advanced colorectal carcinoma is more dependent on lymph node status than on the extent of local invasion. Effective disease control associated with survival in the long term can be achieved by multivisceral resection. PMID- 2218892 TI - Local recurrence after curative resection of colorectal adenocarcinoma. AB - A total of 853 patients with 861 colorectal adenocarcinomas were operated on at our institution between 1965 and 1981. Complete follow-up information was obtained in all but six patients (99.4%), and all available histologic slides were reviewed to determine pathologic stage and characteristics. Six hundred fifty-one patients (76.3%) underwent a potentially curative procedure, and their operative mortality rate was 2.8%. Of the 627 patients available for analysis, 50 (8%) had a local recurrence. The median time to local recurrence was 18 months, and only 16% of local recurrences were diagnosed 5 years after the original resection. Median survival of patients with a local recurrence was 3 1/2 years from the original resection, and 16 patients (32%) survived 5 years or longer. A multivariate logistic regression analysis was conducted to examine the influence of several clinical and pathologic characteristics on local recurrence among Dukes' stages B and C adenocarcinomas (n = 539) after exclusion of patients with synchronous tumors (n = 8), postoperative deaths (n = 18), loss to follow-up (n = 6), or incomplete data (n = 11). This analysis revealed that the local recurrence rate was significantly related to depth of invasion (B1 + C1 = 0%; B2 + C1 = 10%; p less than 0.01), site of origin (right plus transverse colon = 6%; left plus rectosigmoid colon = 10%; rectum = 12%; p less than 0.05), and lymphatic or capillary microinvasion (absent, 6%; present, 14%; p less than 0.05). This analysis attempts to identify patients at high risk for development of local recurrent disease to select candidates for postoperative adjuvant therapy. PMID- 2218893 TI - Follicular cell predominance in the cytologic examination of dominant thyroid nodules indicates a sixty percent incidence of neoplasia. AB - The interpretation of aspiration cytologic smears that contain a predominance of follicular components often presents a dilemma to the clinician who is treating a patient who has a dominant thyroid nodule, especially when thyroid-stimulating hormone suppression does not produce any significant involution of the dominant nodule. We reviewed a consecutive series of 555 fine-needle aspiration cytologic examinations of dominant thyroid nodules. All specimens that contained colloid or follicular cells mixed with lymphocytes or Hurthle cells were excluded from this review. Additionally, nine aspirates contained degenerated follicular cells with insufficient material for cytologic diagnosis. The remaining 76 specimens contained a predominance of follicular cells: 27 specimens were interpreted as containing "normal" follicular cells, and the remaining 49 specimens were read as "atypical" follicular cells. Histopathologic examination of the resected specimens indicated a 60% incidence of neoplasia (30% carcinoma, 30% adenoma) in which the aspiration cytologic study was interpreted as "normal" follicular cells. On the other hand, a 63% incidence of neoplasia (27% carcinoma, 36% adenoma) occurred in which the cytologic study was read as "atypical." In conclusion, aspirates showing a predominance of follicular cells, whether "normal" or "atypical" indicate a 60% incidence of neoplasia in dominant thyroid nodules that do not decrease significantly in size with thyroid-stimulating hormone suppression. PMID- 2218894 TI - Intraoperative parathormone level measurement in the management of hyperparathyroidism. AB - To investigate the potential use of intraoperative intact parathormone measurements to predict curative parathyroidectomy, we measured ionized calcium (Cai) levels and parathormone levels in 33 patients with hyperparathyroidism who underwent exploratory bilateral neck surgery. Nineteen patients each had a solitary adenoma, 13 patients had hyperplasia, and one patient had four normal parathyroid glands. These results were compared to the results for 37 patients who underwent either thyroid lobectomy (TL) (n = 10) or near-total thyroidectomy (NTT) (n = 27) and of 14 control patients who underwent miscellaneous operations. Parathormone decline after curative parathyroidectomy was 86.4 +/- 1.2% (mean +/- SE), which was significantly greater than a decline of 25.7% +/- 9.8% in three patients with persistent postoperative hyperparathyroidism (p less than 0.01). Declines were 38.5% +/- 8.7% after TL (p less than 0.01), 52.2% +/- 5.9% after NTT (p less than 0.01), and 8.3% +/- 4.3% (p less than 0.01), in the control patients. An intraoperative Cai decline of 4.0% +/- 0.6% after curative parathyroidectomy did not differ significantly from the results after TL, NTT, or miscellaneous operations in the control patients. Patients with persistent postoperative hyperparathyroidism had the greatest decline in Cai levels (7.1% +/ 2.3%; p less than 0.05). From these data we conclude that (1) a decline in parathormone level of 70% or more 20 minutes after parathyroidectomy is predictive of cure, (2) thyroidectomy, even unilaterally, produces a significant decline in parathormone level that affects interpretation of intraoperative parathormone level changes, (3) Cai level because of its slow decline is not useful in predicting effective parathyroidectomy, and (4) measurement of intraoperative parathormone level changes should not be used as a substitute for exploratory bilateral neck surgery. PMID- 2218896 TI - [Waiting time for abortion should be removed]. PMID- 2218897 TI - [Danish Council of Nursing--the launching of a professional club]. PMID- 2218895 TI - Assessment of cardiac function in patients who were morbidly obese. AB - Cardiac function of 30 patients who were morbidly obese was studied before bariatric surgery. Twelve patients were studied 13 +/- 4 months after surgery. These patients had a mean age of 37.1 +/- 2.9 years and a body mass index of 50.0 +/- 1.4 kg/m2. Cardiac function was measured by echocardiography, radionuclide angiography scanning, and right heart catheterization. To determine the degree of cardiac dysfunction, the patients were studied with exercise and intravenous fluid challenges. Ultrasonography produced evidence of myocardial thickening with an increased interventricular septum in eight patients (32%) and increased left ventricular mass in 17 patients (53%). The radionuclide scan suggested that morbid obesity was associated with a significantly (p less than 0.05) increased end-diastolic volume and decreased left ventricular ejection fraction as compared with patients who were of normal weight. With exercise the patient who was of normal weight had an increase in the end-diastolic volume, stroke volume, and heart rate, but the patient who was morbidly obese only increased heart rate to produce the necessary increase in cardiac output. Right heart catheterization indicated that the relationship of the pulmonary wedge pressure and the left ventricular stroke work index was abnormal in 14 of 29 patients (48.3%) and depressed in six of 29 patients (20.7%) with exercise. One liter of fluid caused an abnormal relationship of the pulmonary wedge pressure and the left ventricular stroke work index in 12 of 30 patients (40%) and a depressed response in 10 of 30 patients (33.3%). Cardiac studies were repeated in 12 patients after a 54.8 +/- 1.9 kg weight loss. Echocardiography indicated a decrease in dilatation (27.3% to 9.1%) and a significant (p less than 0.05) decrease in hypertrophy (45.5% to 0%). After the weight loss, radionuclide and right heart catheterization studies indicated improved cardiac function with reduced filling pressures and increased left ventricular work during fluid and exercise challenges. These results support the presence of obesity-related cardiomyopathy with ventricular dysfunction, which appears to be caused by a noncompliant ventricle. Significant weight loss achieved with gastroplasty results in increased ventricular compliance and improved cardiac function. PMID- 2218898 TI - [Unemployment insurance. Doubling of unemployed nurses]. PMID- 2218899 TI - [Unemployment insurance. The first billion]. PMID- 2218900 TI - [Denmark's best around-the-clock care automobile]. PMID- 2218901 TI - [Cross-professional health care administration. Interview by Anne Brockenhuus Schack]. PMID- 2218902 TI - [Melkersson-Rosenthal syndrome. Apropos of a clinical case]. PMID- 2218903 TI - [Influence of occlusion on head posture, during periods of continuous intermaxillary pressure]. AB - The influence of divergent splint-adjusted maximum intercuspation on head posture during prolonged phases of clenching was studied in five subjects. During clenching in maximum intercuspation profound changes of head posture were observed, if intercuspation was not harmonized with an upright posture of head and body. Since the interrelation between occlusion and head posture is established a comprehensive approach of orthopedic, physiotherapeutic, and dental measures, in particular for the therapy of myoarthropathy patients with cervical spine symptoms seems appropriate. Occlusal corrections and determination of occlusal relations must always be made or at least checked in the upright relaxed patient with the head straight. PMID- 2218904 TI - [Occlusal rehabilitation in cranio-mandibular dysfunction syndrome with ceramometal restorations]. AB - We present a clinical case of a temporo-mandibular joint dysfunction pain syndrome treated with occlusal rehabilitation consisting on ceramometalic prosthodontic restorations. The result obtained after five years of evolution is excellent, due to the use of adequate technical and clinical procedures together with suitable hygienic habits and the post-treatment establishment of an occlusal splint used exclusively at night. PMID- 2218906 TI - [Kidney involvement in cryoglobulinemia]. AB - The authors provide the reported data on renal impairment in mixed cryoglobulinemia (CGE) and 3 own CGE case reports. Renal impairment by the type of rapid-progressing nephritis with episodes of acute renal failure was the major sign in the clinical picture of those cases. PMID- 2218905 TI - [Kidney involvement in patients with rheumatoid arthritis]. AB - Renal pathology was revealed in 284 out of 498 patients with rheumatoid arthritis (RA) subjected to the 15 years' prospective controlled follow-up and given individualized pharmacotherapy. Biopsy specimens of the kidney were examined in 90 cases. Of these, in 14 patients, they were examined repeatedly. On morphology the following alterations were detected in renal tissue: minimum morphological alterations (18 cases), glomerulonephritis (32 cases), amyloidosis (53 cases), interstitial nephritis (4 cases), and arteriosclerotic nephrosclerosis (1 case). In patients with nephropathy, no pathology nas revealed on morphology (5 cases). Chronic pyelonephritis was diagnosed in 137, nephroptosis in 47, nephrolithiasis in 17, papillary necrosis in 3, and drug nephropathy in 33 patients. Many patients had concomitant renal pathology. Repeated morphological examinations of renal tissue point to dynamic morphological alterations occurring during treatment and disease. Chlorbutin was found to exert a beneficial effect not only on the manifestations of arthritis but also on renal tissue. It could be seen in patients with a primary morphological diagnosis of mesangioproliferative nephritis and minimum morphological alterations in renal tissue. In some cases the clinical and morphological data did not agree, which provides evidence in favour of making renal biopsy in RA patients with a purpose of early diagnosis and specification of renal pathology, choice of the treatment policy. PMID- 2218908 TI - [The combination of diffuse kidney lesions with different diseases of the other organs of the urinary system (the diagnosis, characteristics of the course and outcomes)]. AB - The author characterizes in detail 4340 patients with diffuse renal lesions (chronic glomerulonephritis, renal amyloidosis, lupoid nephritis, diabetic glomerulosclerosis and nephrosclerosis) coupled with different diseases of the urinary organs including urolithiasis, cancerous and tuberculous processes, purulent diseases of the kidneys and prostatic lesions. Stage III chronic renal failure (CRF) was revealed in 2073 (57.1%) out of the 4340 patients. All of them died because of uremia. The mean lifespan of the patients was 1.6 +/- 0.1 yr. since manifestation of the concomitant process. The shortest times of CRF onset, the highest frequency of stage III CRF and the least lifespan were noted in patients with double association, particularly in those suffering from associated chronic glomerulonephritis with renal amyloidosis and urinary bladder cancer in the stage of compression with tumor of the intramural parts of the ureters, namely they were 0.6 +/- 0.1, 100% and 1.0 +/- 0.1 yr., respectively. The author holds that the main reason for such an abrupt CRF onset in patients with concomitant renal lesions of any type lies in simultaneous combined influence on the kidneys of absolutely different diseases bearing in mind their etiology and pathogenesis. Besides, according to the author's data, considerable influences on the times of CRF onset and rates of its progress are produced by both the course and stage (phase) of the development of each of the coexistent diseases. Attention is drawn to the necessity of early participation of urologists in the solution of the problems concerned with the policy of managing nephrological patients with diseases of other organs of the urinary system as well as with permanent dynamic follow-up of all the patients with concomitant processes, especially with double ones. PMID- 2218907 TI - [New markers of collagen and basal membrane metabolism and kidney involvement in systemic scleroderma]. AB - The study was made within the framework of the Soviet-Finnish cooperation and represents a fragment of work pertaining to the clinical trials of new markers of metabolism of collagen and basal membranes in patients afflicted with systemic scleroderma (SSD). Sufficient clinical material (84 SSD patients) and radioimmunoassays were employed to study the clinical significance of aminoterminal propeptide of type III procollagen. In SSD patients with renal impairment (n = 34) and without it, PIIINP and PIIINP-Fab, serum galactosyl hydroxylysylglucosyltransferase and two antigens of basal membranes-7S-domene of type IV collagen and PI-fragment of laminine were determined. Renal impairment was established to correlate with serum concentration of PIIINP-Fab (p less than 0.007). PI-fragment of laminine. The parameters under study correlated as well with the disease course, the presence of arthritis and the Raynaud's syndrome gravity and can be regarded as markers of the disease activity and high fibrous formation lying at the basis of SSD. PMID- 2218909 TI - [The malignant hypertension syndrome: incontrovertible and questionable truths]. AB - A total of 42 patients with malignant arterial hypertension (MAH) were examined. Of these, 32 patients had essential hypertension (26 with normal renal function and 6 with renal failure treated by programmed hemodialysis) and 10 suffered from chronic glomerulonephritis. The patients were examined for central hemodynamics, hormonal background (plasma renin activity) (PRA), plasma aldosterone and cortisol concentration. 14 patients underwent closed puncture biopsy of the kidneys. All the patients manifested high PRA associated activation of gluco- and mineralocorticoid adrenal function along with the hyperkinetic syndrome. MAH was characterized by dramatic discrepancy between the stroke and cardiac indices and specific peripheral resistance. Nephrosclerosis whose extent varied, attaining maximum in patients with associated essential hypertension and renal failure and in autopsy material, in addition to severe lesions of the renal vessels appeared to be the common feature of all morphological alterations. Plasmic impregnation and fibrinoid necrosis of the arterioles were not detectable in all the patients, being of focal character. The same alterations were identified in the patients during exacerbation of glomerulonephritis and in the absence of MAH. The data obtained point to the nonuniformity of MAH. Four clinicomorphological variants of MAH are suggested. PMID- 2218910 TI - [Na-Li countertransport and the diagnosis of hypertension and combined hypertension and renal artery stenosis]. AB - The rate of Na-Li countertransport was studied in inpatients with essential hypertension (n = 59), chronic diffuse glomerulonephritis (n = 30), chronic pyelonephritis (n = 26), renovascular hypertension (n = 15) and in those with associated renovascular hypertension and essential hypertension (n = 4). Multiple regression analysis has demonstrated that age, body weight and blood plasma lipids do not make any significant contribution to dispersion of the counter transport rate. The mean rate of countertransport in patients with essential hypertension turned out much higher than that in patients with secondary hypertensions. Repeated examinations have shown that in every man, the countertransport rate remains unchanged for 1.5 yr. It is not affected either by hypotensive therapy or surgical treatment. In inpatients with secondary hypertension and low rates of countertransport, high arterial pressure (AP) drops after surgical treatment of the kidneys, renal vessels or adrenals. Surgical treatment of patients with secondary hypertension and high rates of countertransport does not lead to any material decrease of AP. It is assumed that the rate of Na-Li countertransport can be used for diagnosing associated secondary hypertensions and essential hypertension and prediction of AP lowering after surgical treatment. PMID- 2218911 TI - [The determination of the separate intrarenal hemodynamics and its place in the diagnosis of nephrogenic arterial hypertension]. AB - Differential diagnosis between essential hypertension and secondary arterial hypertension (AH) that developed in the presence of chronic pyelonephritis was made in 12 patients with AH and the urinary syndrome (leukocyturia and bacteriuria). With that purpose in view for revealing functional renal asymmetry, a study was made of the effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in each kidney separately based on computation of 99Tc-DTPA and 131I-hippuran clearances. Some patients in whom AH was later regarded as essential manifested practically equal values of the ERPF and GFR from both sides, with the real characteristics of the latter ones being little different from the respective populational values calculated by computer bearing in mind the body surface of those patients. The other patients' group showed, along with a decrease of the total ERPF and GFR, a dramatic asymmetry of the intrarenal hemodynamics of both ERPF and GFR, which is fairly characteristic of chronic pyelonephritis. This allows the syndrome of AH to be regarded in those patients as secondary. PMID- 2218912 TI - [Acute nephrological situations in the physician's practice]. PMID- 2218913 TI - [The current procedures in the treatment of amyloidosis]. PMID- 2218915 TI - [The development of rapidly progressing glomerulonephritis in a patient with systemic atherosclerosis and hyperlipidemia type IV]. PMID- 2218914 TI - [A case of Meyer-Betz's syndrome complicated by acute kidney failure]. PMID- 2218916 TI - [Eosinophilic vasculitis: the diagnostic difficulties]. PMID- 2218917 TI - [Nephrotic hyperlipidemia and its clinical significance]. PMID- 2218918 TI - [The nephrological aspects of infection with the human immunodeficiency virus]. PMID- 2218919 TI - [The outcomes and prognosis of a course of acute glomerulonephritis]. AB - Observation of 131 patients with acute glomerulonephritis (AGN) experiencing the first year of disease made it possible to distinguish, by the 4th month of disease, the lingering disease patterns encountered in 100% of cases with the nephrotic form and typical for pronounced and little symptomatic AGN (96.1 78.8%). As compared to the catamnestic data, 83 patients manifested (after 5.8 +/ 0.7 yr.) an unfavourable influence of the lingering disease course on AGN outcomes (the probability of convalescence dropped to 30.8-33.3% in pronounced and little symptomatic forms and was completely excluded in the nephrotic one) and a high diagnostic significance of the dynamics of the urinary syndrome for prognosis determination. The constancy of proteinuria at a level of over 1 g/day and hematuria at a level over 50.0 x 10(3)/ml within 4 to 6 months significantly deteriorated the prognosis. Virus nature of pronounced AGN can be indicated among other prognostic criteria. The other characteristics of the debut produced no significant effect on the disease outcome. The morphological signs of the chronic disease corresponded to mesangiomembranous glomerulonephritis whereas fibroplastic alterations were only observed in special forms of AGN marked by rapid progress. PMID- 2218920 TI - [Clinico-morphological variants of mesangioproliferative glomerulonephritis]. PMID- 2218922 TI - [The nephrological aspects of gerontology]. PMID- 2218921 TI - [The prognostic significance of the morphological and clinical characteristics of chronic glomerulonephritis]. AB - In 520 patients followed up for 4 to 20 years a study was made of the relationship between the actual survival time and the morphological and clinical characteristics of chronic glomerulonephritis. A well-defined parallelism was established between the rate of disease progress and the rate of exacerbations as was an unfavorable prognostic importance of marked tubulointerstitial lesions and glomerular sclerosis, which was more manifest in frequent relapses. Considerable differences in the survival of patients with hypertension or associated hypertension and the nephrotic syndrome with varying process activity do not provide evidence in favour of their direct influence on the rate of the disease progress. As far as certain morphological patterns of glomerulonephritis are concerned, the prognosis is different because of specific clinical manifestations and anatomic alterations common to each disease pattern. PMID- 2218923 TI - [The effect of pregnancy on the course of different clinical forms and morphological variants of primary chronic glomerulonephritis]. AB - The author relates the data on the time-course of changes in diurnal proteinuria, diastolic arterial pressure and blood creatinine in 123 patients with primary chronic glomerulonephritis seen during 159 pregnancies. The dependence of the character of those changes on the respective parameters before conception was analyzed as was such a dependence, in part of the patients, on the morphological disease pattern. The rise of proteinuria and diastolic arterial pressure during gestation was seen more often in women with initial diurnal protein losses exceeding 1g and with arterial hypertension that occurred before pregnancy. The rise of blood creatinine before conception was a prognostically unfavourable sign. Mesangiocapillary glomerulonephritis occurring in the gestation period is viewed as less favourable as compared to mesangioproliferative glomerulonephritis. PMID- 2218924 TI - [A clinico-pathogenetic approach to choosing the therapeutic procedure in chronic glomerulonephritis]. AB - The results have been compared of the use of two schedules (continuous and cyclic) of multimodality therapy of chronic glomerulonephritis (CGN) including cytostatics, corticosteroids, anticoagulants and deaggregation agents. Continuous therapy was carried out for 12.9 +/- 0.41 months on the average, with the drug dosage being corrected depending on the clinico-laboratory and immunological findings as well as on the parameters of the hemostatic system. Cyclic therapy was conducted for 6 months according to a strictly unified program. It has been shown that continuous individualized treatment compares very favourably with the cyclic schedule, which is particularly marked in mesangiocapillary CGN and CGN with a tubulointerstitial component. It is concluded that continuous multimodality treatment chosen with regard to the clinico-pathogenetic disease characteristics allows CGN prognosis to be improved. PMID- 2218926 TI - [Rapidly progressing lupus nephritis]. PMID- 2218925 TI - [The catamnestic assessment of the efficacy of combined pathogenetic therapy in patients with different clinico-morphological variants of chronic glomerulonephritis]. AB - In 70 patients with functionally compensated chronic glomerulonephritis (CGN), the disease outcomes were elucidated after the use of the 4-component therapy (a cytostatic, an anticoagulant, an antiaggregation agent and prednisone). The therapy appeared much more effective in the nephrotic types of CGN than in the active nephritic types. Remission was only attained in a subgroup of patients with the active types: with an early stage of the maximally active type of mesangiocapillary CGN. In the nephrotic type CGN, the therapy was effective in short-phase disease and ineffective in long persistence of that syndrome. In the nephrotic types, mesangioproliferative CGN as well as the short-phase nephrotic syndrome irrespective of the morphological type turned out predictors of a favourable outcome following the treatment. No effect can be predicted in focal segmental hyalinosis/sclerosis accompanied by arterial hypertension and the protracted nephrotic syndrome. PMID- 2218927 TI - [The use of ultrahigh doses of corticosteroids in treating the most severe variants of lupus nephritis]. AB - The authors analyze the 10-year experience gained with the use of steroid pulse therapy for the gravest forms of lupus nephritis--rapid-progressing lupus nephritis and active lupus nephritis associated with the nephrotic syndrome. Ultrahigh doses of prednisolone and methylprednisolone (1000 mg i. v. for 3 days) was monotherapy or as a constituent part of multimodality treatment were given to 30 patients including 27 women and 3 men aged 18 to 48 years. Of these, 12 patients had rapid-progressing lupus nephritis and 18 active lupus nephritis. The short-term treatment results were estimated after 1 to 3 months, whereas the long term ones after 12 months to 9 years. Analysis of the treatment results allows the following conclusions to be drawn: the use of steroid pulse-therapy was monotherapy is only justified in patients suffering from active lupus nephritis with the nephrotic syndrome without renal failure and only at the disease debut. In rapid-progressing lupus nephritis and long active lupus nephritis with the phenomena of renal failure, the positive effect can only be attained after combination of steroid pulse therapy and high doses of prednisolone per os or long intake of cytostatics per os or in the form of cytostatic pulses. PMID- 2218928 TI - [The role of the kidney lymphatic capillaries in the pathogenesis of the nephrotic syndrome]. AB - As many as 16 patients with nephrotic syndrome (NS) of varying etiology and 10 patients without the NS were examined for ultrastructure of lymph capillaries of the kidney. Many-staged changes, from regenerative to destructive ones, associated with proteinuria growth and formation of the NS were revealed in lymph capillaries of the kidney. Patients with the NS of long standing manifested irreversible destructive processes--destruction of the capillary walls, karyopyknosis and cytoplasm coagulation. Microcirculatory disorders may be regarded as one of the mechanisms implicated in nephropathy progress. PMID- 2218929 TI - [The renal functional reserve in the nephrotic syndrome]. AB - Functional reserves of the kidneys (FRK) were examined in 29 patients with the nephrotic syndrome and in 14 healthy subjects. FRK were determined as the degree of the increase of endogenous creatinine clearance after stimulation with beef protein (0.7 g per kg bw) or dopamine (3 micrograms/min per kg bw). It was revealed that in 2/3 of the patients, FRK were lowered or lacking. The lack of FRK was seen in all the morphological varieties of renal lesions, with the frequency being greater in the severe clinical forms of the nephrotic syndrome, in lasting nephropathy, in association with arterial hypertension or renal failure. It has been noted that FRK may recover after successful treatment of the nephrotic syndrome, attesting to a favourable regimen of organ functioning and suggesting deceleration of the tempo of renal disease progress. PMID- 2218930 TI - [The chemotactic characteristics of the leukocytes and fibroblasts in amyloidosis]. AB - Altogether 44 patients with amyloidosis (7 with primary, 24 with secondary and 13 with hereditary associated with periodic disease) and different stages of renal impairment and 32 patients with chronic glomerulonephritis (CGN) (14 with the latent and 18 with the nephrotic form) were examined for chemotactic properties of peripheral blood leukocytes and skin fibroblasts in Boyden's chambers. Chemotaxis of leukocytes from patients with different clinical forms of amyloidosis was found to be decreased. That decrease manifested itself even at the proteinuric stage of renal impairment. Addition of autologous serum brought about another decrease of the chemotactic response of leukocytes. There was a lowering of chemotaxis of cultivated skin fibroblasts from amyloidosis patients, which remained unchanged on repeated cell passages. Chemotactic activity of cultivated fibroblasts from CGN patients did not differ from that of healthy persons' fibroblasts and embryonal fibroblast strain. Possible causes of the alterations revealed are discussed. PMID- 2218931 TI - [Richard Bright and the problems of modern nephrology (on the 200th anniversary of the birth of R. Bright)]. PMID- 2218932 TI - [The epidemiological aspect of chronic kidney lesions of drug origin]. AB - In order to establish the prevalence of the intake of the most widely used nephrotropic drugs (non-steroidal anti-inflammatory agents and analgesic antipyretic drugs), the authors have carried out epidemiological studies among the urban population. 5996 persons living in Riga were examined according to the designed by the authors 4-staged system using computer at the final stage. All the examined underwent analysis of the morning portion of urine. The drugs indicated were discovered to be taken for a long time in 14% of cases (in 15.4 among women and in 11.8% among men). The use of the drugs was motivated by degenerative dystrophic alterations in the bones and joints (56.27%), complicated virus infections (9.68%), headache (2.99%), and by combination of the three enumerated causes (30.34%). In 0.72% of cases, the causes of drug intake could not be established. Depending on the presence of a concrete urinary symptom, a high relative and a high absolute risk of the development of chronic tubulointerstitial renal lesions provoked by drugs have been defined in cases of the prolonged use of the drugs under study. PMID- 2218934 TI - [The use of enterosorption in the combined therapy of patients with urolithiasis complicated by chronic kidney failure]. AB - The results of conservative treatment of 51 patients with urolithiasis complicated by chronic renal failure in the intermittent stage have been analyzed. There were two groups of patients. The first one included 36 patients receiving enterosorption in addition to routine multimodality treatment. The second group was made up of 15 patients who did not undergo enterosorption which consisted in oral application of SKH-1K coal in a dose of 10 to 15 g 3 times a day 1.5 h after meal for 10 days. The treatment efficacy was judged from the patients' general health status, central hemodynamics (cardiac index and peripheral vascular resistance), the level of azotemia, and the content of medium sized molecules. As shown by the data obtained, the multimodality treatment coupled with enterosorption produced an appreciable improvement of the patients' health status, reduction of the signs of intoxication, while the level of medium sized molecules and creatinine reached the control. The hypokinetic circulatory syndrome seen before the treatment disappeared. At the same time the second group patients retained the high level of azotemia, whereas the content of medium-sized molecules remained increased. Besides, they demonstrated the hypokinetic circulatory syndrome. It is thus recommended that enterosorption be applied to the treatment of patients with chronic renal failure. PMID- 2218933 TI - [Changes in the thrombocyte and plasma factors of hemostasis in amyloidosis]. PMID- 2218936 TI - [The effect of acetate and bicarbonate hemodialysis on protein and lipid metabolism in patients with chronic kidney failure]. AB - In 26 patients with chronic renal failure undergoing hemodialysis, use was made of an acetate solution (40 mmol/l) and in 7 patients, of a bicarbonate solution (35 mmol/l). The control group was made up of 20 healthy volunteers. In addition to better tolerance, the bicarbonate dialysis favoured adequate correction of acid-base balance, normalization of hypercholesterolemia, lowering of the rate of protein degradation. Among patients on the acetate dialysis, subgroups with normal (9 persons) and delayed (17 persons) acetate utilization were distinguished. A close relationship was discovered between blood acetate concentration before procedure and the rate of urea generation (r = +0.79, p less than 0.05). It is assumed that the acetate dialysis intolerance is determined by protein hypercatabolism under the conditions of delayed utilization of acetate by the peripheral tissues. PMID- 2218935 TI - [Disordered lipid metabolism and the morphofunctional instability of the erythrocyte membranes in patients with terminal kidney failure]. AB - Fifty-two patients with terminal renal failure (TRF) placed on elective hemodialysis were examined for serum lipids and red blood cell membranes with the aid of chromatographic separation of lipids in thin-layer silica gel on Silufol plates followed by densitometry. Spectrocytophotometry was employed to study red blood cell distribution on the basis of the content of lipoproteins in TRF patients. Fluidity of the lipid bilayer of the red blood cell membrane was measured on Hitachi spectrofluorimeter according to the degree of eximerization of fluorescent pyrene. Dyslipidemia manifested itself as hyperlipidemia, hypertriglyceridemia, hypercholesterolemia and hyperphosphatidylcholinemia. The lipid profile of the red blood cell membranes was found to be deranged, which was evidenced by the reduced content of lipoproteins, total phospholipids, triglycerides, and cholesterol esters. In addition, there was a significant rise in the content of free cholesterol, lysolecithin and phosphatidyl ethanolamine. Impairment of lipid exchange between blood serum and the red blood cell membrane in TRF patients is under discussion. The changes in the lipid spectrum of the red blood cell membranes mirror their morphofunctional failure, supported by derangement of fluidity of the lipid bilayer of the red blood cell membrane. Both increase of viscosity of the lipid bilayer of the red blood cell membrane caused by a high level of cholesterol in the membrane and changes in the cholesterol/phospholipid ratio and reduction of the lipid bilayer viscosity related to the rise of the content of membrane lysolecithin in part of TRF patients were discovered. Hemodialysis influenced the lipid content of blood serum, producing no effect on the lipid spectrum of the red blood cells membrane. PMID- 2218938 TI - [The outpatient management of patients with a transplanted kidney]. AB - Organization of the management of outpatients with a transplanted kidney is described. The basis of such organization is formed by documentation of the patients' status during the entire observation period in a special card containing the data on the donor; distant monitoring of cyclosporin A for patients living far from the clinic; training of patients. The main complications that occur in patients with a transplanted kidney in the long-term postoperative period are related. They are pyelonephritis of the transplant, essential hypertension and symptomatic hypererythrocytosis. The 2-year survival of the patients is 70.8%, that of the transplant 73.1%. PMID- 2218937 TI - [The diagnosis of cyclosporin nephrotoxicity in patients after kidney transplantation]. AB - The authors review possibilities of thin needle aspiration biopsy of renal allotransplants in the diagnosis of cyclosporin nephrotoxicity. 151 thin needle aspiration biopsy specimens were explored in 55 patients following kidney transplantation. According to the authors, this method when applied in the early postoperative period may turn an informative one. However, if the time elapsed after operation exceeds 3 months, they recommend performing puncture biopsy of renal transplants. PMID- 2218940 TI - Expression of Veratrum alkaloid teratogenicity in the mouse. AB - Jervine, a steroidal alkaloid found as a minor constituent in the teratogenic range plant Veratrum californicum, has produced similar terata in sheep, rabbit, hamster, and chick, although the sensitivity to the alkaloid varies in the different species. Sprague Dawley rats and Swiss Webster mice are relatively insensitive. The aim of this study was to determine the teratogenic potential of jervine in three strains of mice and to ascertain if the response is strain dependent. One strain, Swiss N:GP(S), was retested since a Swiss Webster strain had been found previously to be jervine-resistant. In addition, we tested C57BL/6J and A/J, which are known to differ in their response to the teratogenic action of steroids and vitamin A. Mice were treated by gavage with single doses of jervine (70, 150, or 300 mg/kg body weight) on either day 8, 9, or 10 of gestation. Jervine was teratogenic to C57BL/6J and A/J mice but not to N:GP(S). The induced terata included cleft lip with or without cleft palate, isolated cleft palate, mandibular micrognathia or agnathia, and limb malformations. Fetal teratogenicity and maternal and fetal toxicity were highly correlated. The prevalence of each defect and fetal death was a function of strain, dose, and time of treatment. Maternal death was higher in C57BL/6J than in A/J mice. Although some of the terata were similar, the response pattern between strains was different from corticosteroids and vitamin A for both sensitive period and the strain dose response. An effect on differentiation of chondrocyte precursors may account for many of the defects, but an earlier lethal effect on differentiation of neural crest cells or precordal mesenchyme may also occur. PMID- 2218939 TI - [The clinico-morphological characteristics of psoriatic nephropathy]. AB - Based on studying the data obtained during examination of patients with psoriasis combined with the urinary syndrome possible varieties of psoriatic nephropathy, namely chronic glomerulonephritis (CGN) and amyloidosis were distinguished. CGN combined with psoriasis was mainly represented by latent glomerulonephritis (GN) and morphologically, it was mostly represented by the mesangio-proliferative variant, with IgA and C3 being fixed on the basal membrane of the capillaries and in the mesangium. The clinicomorphological feature of that form of psoriatic GN is combination of the signs of both associated CGN and hyperuricemia and IgA nephritis. Special emphasis is laid on the diagnosis of rapid-progressing GN which is of paramount importance for institution of early etiopathogenetic therapy. Amyloidosis associated with psoriasis is characterized by the signs of acquired disease (AA-amyloidosis) and does not differ in its course from amyloidosis coupled with other diseases. PMID- 2218941 TI - Abnormal limb regeneration in adult newts exposed to a pulsed electromagnetic field. AB - This investigation examined two questions: 1) whether or not forelimb regeneration results in a faithful replacement of the distal skeletal pattern and 2) what effect exposure to a pulsed electromagnetic field (PEMF), the type reported to facilitate healing of human non-united bone fractures, would have on the process of limb regeneration. Of the native forelimbs, 98% (132 out 134) had a skeletal pattern that showed little difference with the only variation being the range of carpal bones (5-8). Following a 4-5 month postamputation period, the skeletal pattern of the normal regenerates was examined. While 72% (135 out of 188) of these forelimbs resembled the native group, 28% (53 out of 188) were abnormal. These abnormalities consisted of the loss of a digit, fused carpals, and long bone defects which occurred singly or in combination with one another. Exposure to a PEMF for the first 30 days postamputation, followed by a 3-4 month postamputation period, produced in addition to the normal (60%, 144 out of 240) and abnormal forelimbs (28%, 67 out of 240), a group of forelimbs with unique gross defects (12%, 28 out of 240). These defects, occurring singly or in combination, included the loss of two or more digits with associated loss of carpals, absence of the entire hand pattern, and abnormalities associated with the radius and ulna. We can offer no explanation for these observations. PMID- 2218942 TI - Protein alterations associated with N-methyl-N-nitrosourea exposure of preimplantation mouse embryos transferred to surrogate mothers. AB - Mouse preimplantation embryo functions have been shown to be disrupted by in vitro exposure to N-methyl-N-nitrosourea (MNU) with subsequent transfer to the uteri of pseudopregnant surrogate mothers. Increased gross malformations and decreased fetal body lengths in the midgestational period have been previously documented. Protein extracts were isolated from day 12 mouse fetuses developed from MNU- or solvent-exposed blastocysts and analyzed by two-dimensional electrophoresis. The electrophoretic patterns reveal six protein alterations in day 12 fetal tissue induced by MNU treatment at the blastocyst stage. Five of these alterations involve shifts in isoelectric point (pI) and the other alteration involves a quantitative increase in a protein. The possibility that two of the proteins which exhibit a shift in pI following MNU exposure represent the cell adhesion molecules, N-CAM and L-CAM (based on similar Mr values), was investigated by Western blot analysis. No pI alteration in L-CAM or N-CAM expression is seen after MNU exposure. These results demonstrate that in vitro MNU exposure of preimplantation embryos results in protein alterations in midgestational fetuses. Thus, the effects of MNU exposure on preimplantation embryos may be manifest long after exposure, and subtle, non-lethal mutations may play a role in poor fetal outcome after early chemical exposure. PMID- 2218943 TI - Effects of pulsing electromagnetic fields on the prenatal and postnatal development in mice and rats: in vivo and in vitro studies. AB - Electromagnetic fields (EMF) might have various biological effects on the developing embryo. We studied the effects of pulsing electromagnetic fields (PEMF) on the in vitro development of preimplantation mouse embryos and of early somite rat embryos as well as on the in vivo development of rat embryos. We used PEMF at frequencies of 1, 20, 50, 70, and 100 Hz with a tension of 0.6 V/m. The embryos were exposed to PEMF throughout the experimental period. PEMF at frequencies of 20 and 50 Hz were embryotoxic, inhibiting over 50% of blastocysts from hatching and further development, all within 72 h of culture. PEMF at frequencies of 50 and 70 Hz induced 22% and 30% incidence of malformations in 10.5 day old rat embryos after 48 h in culture. The main malformations were absence of telencephalic, optic, and otic vesicles and of forelimb buds. In addition, retarded growth and development manifested by fewer somites, reduction in crown-rump length, and retarded closure of the neural tube were found in many embryos. No significant pathological changes were found by TEM in PEMF-exposed embryos. Disappearance of microvilli and collapse of apical parts of endodermal cells were observed by SEM in many yolk sacs of embryos exposed to 50 and 70 Hz PEMF. A slightly reduced litter average, a reduction or increase of weight, and a delay in eye opening was observed among offspring of pregnant rats exposed throughout pregnancy to PEMF at frequencies of 20, 50, and 100 Hz. No malformations were observed among these offspring. The mechanism of PEMF-induced embryotoxicity and teratogeneity is unknown, as is the mechanism of the "protective effects" of the mother on the rat embryos exposed to PEMF in vivo. PMID- 2218944 TI - Delayed neural crest cell emigration from Sp and Spd mouse neural tube explants. AB - Splotch (Sp) and splotch-delayed (Spd) are allelic mutations on chromosome 1 of the mouse. Embryos homozygous for either allele have neural tube defects (NTDs) and deficiencies in neural crest cell (NCC) derived structures. The fact that Spd mouse mutants sometimes have deficiencies in NCC derivatives in the absence of an NTD led to the hypothesis that neurulation and the release of NCCs may depend on a regulatory event that is common to both processes. Therefore, it may be possible to understand the cause of NTDs in these mutants by examining the basis of aberrant NCC derivatives. Caudal neural tubes were excised from day 9 Sp and Spd embryos and placed into gelatin-coated tissue culture dishes, or 3 dimensional basement membrane matrigel, and cultured for 72 hours. A cytogenetic marker was used to genotype the embryos. In planar cultures, no morphological differences were observed between NCCs from neural tube explants of Spd mutants compared to those from heterozygous or wild-type embryos. However, there appeared to be a delay in the release of NCCs from the neural tube in both Sp and Spd mutants, which was particularly evident in Sp. After 24 hours in culture, the extent of NCC outgrowth, as well as the number of NCCs emigrating from explanted neural tubes, was significantly lower in Sp and Spd mutant cultures than in controls. No differences were observed in the mitotic indices among cells which had emigrated. By 72 hours, mutant cultures and their non-mutant counterparts were similar in terms of outgrowth, cell number, and migratory capability. After 24 hours in 3-dimensional basement membrane matrigel, cell outgrowth from Sp explants was also significantly less than controls. The pattern of NCC outgrowth in both types of culture conditions indicates a 24 hour delay in mutant cultures compared to controls. This stems from a delay in the release of NCCs from the neural tube, suggesting that the defect lies within the neuroepithelium with respect to the release of NCCs. PMID- 2218946 TI - Stings and bites revisited. PMID- 2218945 TI - Expression of a new mutation (Axd) causing axial defects in mice correlates with maternal phenotype and age. AB - A new autosomal mutation, Axd (axial defects), is described. Axd segregates in a simple Mendelian fashion, and it is dominant with incomplete penetrance and variable expressivity. The phenotype of Axd heterozygotes ranges from a variety of tail anomalies to visibly normal tails. Approximately 12% of neonates from curly-tail (CT) F1 (Axd/+) x F1 (Axd/+) matings exhibit open neural tube defects (NTD) in the lumbosacral region and 16% have curly tails. Mean litter sizes and resorption rates comparable to wild type indicate that homozygosity for Axd is not obligately lethal. Genetic background plays a major role in Axd expression. Strains such as BALB/cByJ allow the highest penetrance of the mutation in single dose (46%), whereas, in CF-1 mice Axd is recessive. The tail phenotype of heterozygous Axd/+ dams, in part reflective of their genetic background, correlates with the incidence of NTD in F2 offspring: CT mothers produce significantly more neonates with frank NTD than normal tail mothers. At the one embryonic period examined for this study (D13/D14 post-coitus), an 85% higher incidence of total axial defects is observed than among the F2 at birth. Unchanging litter size and the relative increase in phenotypically normal offspring by birth suggest that Axd acts by delaying posterior neural tube closure. One of the most significant findings in this study is that maternal age influences the survival of Axd embryos in utero. Axd/+ dams older than 8 months yield fewer mean implants, higher resorption rates, and fewer viable embryos with axial defects than do Axd/+ dams younger than 8 months. Axd is not allelic to nor linked to the Sp (splotch) gene which also affects neurulation. PMID- 2218947 TI - Alprazolam withdrawal. PMID- 2218948 TI - TMA, AMA respond to blood banks' legal problems. PMID- 2218949 TI - Transfer law puts rural internist between a rock and a hard place. PMID- 2218950 TI - Disciplining doctors in Texas: the Texas State Board of Medical Examiners. PMID- 2218951 TI - The National Practitioner Data Bank, part II: Questions on problem areas. PMID- 2218952 TI - Where are tomorrow's scientists? PMID- 2218953 TI - Texas Tech MEDNET completes its first 'unplanned' video consult. PMID- 2218954 TI - Where is AIDS research taking us? PMID- 2218955 TI - TDH warns physicians: raw seafood may be dangerous menu item. PMID- 2218956 TI - AMA takes stand on pregnant woman's right to refuse treatment. PMID- 2218958 TI - Texas HMOs and PPOs: coming on strong in the '90s. PMID- 2218957 TI - Postoperative infections at Texas hospital prompt drug warning. PMID- 2218959 TI - West Texas teenagers and AIDS: a survey of their knowledge, attitudes, behavioral changes, and information sources. AB - We conducted this study to determine the knowledge, attitudes, behaviors, and sources of AIDS information among teenagers in West Texas. We also examined differences by gender, ethnicity, and rural/urban status. Results were divided into the following categories: general knowledge of AIDS, AIDS-related attitudes, behavior changes caused by AIDS, and AIDS information sources. The 289 ninth grade students revealed a greater knowledge of AIDS than had been shown in studies in other states. However, there were group differences with Anglo students exhibiting greater knowledge of AIDS. There were also some differences between rural and urban students, with urban students scoring higher on knowledge. Finally, doctors were regarded as the most reliable source of AIDS information. There were many implications related to AIDS education from these results and from the other findings in this study. PMID- 2218960 TI - Legal issues, AIDS, and the practicing physician. AB - This article highlights for the practicing physician some of the more important laws and regulations related to and arising from the AIDS epidemic. Medical-legal issues regarding the availability of health care as defined by federal and state law regarding employment and level of medical care given based on HIV status is discussed. Texas law regarding testing, disclosure of test results, and possible claims that could arise due to issues such as the invasion of privacy are examined along with criminal penalties for transmitting the virus to others, insurance, and insurability. Finally, the June 1989 Human Immunodeficiency Virus Services Act and Senate Omnibus Bill 959, which was passed into law, is briefly outlined. PMID- 2218961 TI - The "seed and soil" hypothesis and the decline of radical surgery: a surgeon's opinion. AB - Controlled, clinical trials have demonstrated that recurrent breast cancer following lumpectomy may pose little risk to patient survival. There is no generally accepted biologic explanation of this dilemma. One hundred years ago Paget proposed the "seed and soil" hypothesis to describe the variation among organs in their susceptibility to tumor metastasis. This paper defines his hypothesis in a manner which attempts to explain the dilemma of local recurrence. Since individuals vary widely in their levels of natural killer (NK) cytotoxicity, they may also vary widely in their susceptibility to disseminating tumor cells. Patients who survive their initial tumor without developing distant metastases can be expected to survive a recurrence arising from residual tumor cells of the primary lesion. The "seed and soil" hypothesis supports "preservation" surgery in the treatment of malignant disease. Patients who develop distant metastases early in the course of their disease are like fertile soil for circulating tumor cells. Patients who resist the development of distant metastases are like barren soil. PMID- 2218962 TI - [Does your patient take his medicine? Compliance problems in clinical practice]. AB - There is convincing evidence from compliance research that deviations from the prescribed drug regimen is the rule rather than the exception. Demographic and psychosocial patient factors poorly correlate with non-compliance, whereas features of the disease, mechanisms of treatments, regimens and the patient physician interaction are particularly important determinants of patients' compliance behaviour. Non-compliance can not be predicted. There are problems in the assessment of non-compliance, more particularly of its clinical consequences. New microprocessor-based technology evaluated essential insight into patients' compliance behaviour and revealed different patterns of non-compliance. On one hand, the therapeutic outcome can be impaired by non-compliance, on the other hand, however, certain patterns of non-compliance appear to be appropriated from the patients' point of view. In medical practice it is important to consider non compliance as essential impact on drug therapy and to promote the discussion of this issue with patients. PMID- 2218963 TI - [Current problems in practical pharmacotherapy]. PMID- 2218965 TI - [Pharmacogenetics for the practicing physician]. AB - An important source of interindividual differences in drug action are inherited differences in the pharmacokinetics and pharmacodynamics of many drugs. Besides some well-known but rarely occurring examples of unusual drug action, the inherited variations of drug metabolism are of particular clinical importance, as a relationship between the defect of metabolism and the effects and toxicity of the drugs involved has been observed. Recent investigations were able to elucidate many of the molecular mechanisms responsible for these genetic defects. PMID- 2218964 TI - [Monitoring of therapy using drug concentration levels: Why? When? How?]. AB - Serum concentration measurements represent a tool that can help the physician to choose the optimal dose in an individual patient. Its application has been recommended for several drugs that show a narrow therapeutic range and for which the dose cannot be individually adjusted directly on the basis of the therapeutic effect. For an effective use of his therapeutic tool, it is important to observe the following three points: 1. The dosage history must be known, including patient's compliance. 2. Whenever possible, the measurement should be obtained after steady-state has been reached on a constant dosing regimen (four half-lives of the drug). The dose adjustment in steady-state is very simple: The concentration changes are for most drugs proportional to the changes in dose rate. 3. The dose adjustment should never be performed on the basis of the concentration measurement alone, but always in the context of the clinical conditions and the patient's response. PMID- 2218966 TI - [Aspirin against aging? For whom and how much?]. AB - Aspirin has been successfully used in the secondary prophylaxis of myocardial infarction, cerebral vascular events and peripheral arterial disease. Regular aspirin intake may further be beneficial in asymptomatic healthy male with cardiovascular risk factors over the age of 50. There is no good evidence that aspirin prevents the development of atherosclerosis and thromboembolic events in healthy individuals. PMID- 2218967 TI - [Antiviral substances: against what? For whom?]. AB - Acyclovir and zidovudine are the two most widely used antiviral drugs. Acyclovir is efficacious against all infections caused by herpes simplex virus, but treatment must start early to be effective. Herpes zoster virus is less susceptible to acyclovir, but high doses shorten the duration of skin lesions, although the effect on post-herpetic neuralgia is uncertain. Zidovudine diminishes short-term mortality in patients with HIV infection and serious opportunistic infections. In those patients, the average increase in life expectancy is about one year. Because of myelotoxicity, frequent monitoring of blood counts is necessary. Recent results in patients who have few or no symptoms of HIV infection indicate that the drug decreases the chance of progressing to AIDS. Therefore, indications for treatment now include asymptomatic patients with unfavourable laboratory parameters. PMID- 2218968 TI - [Antimycotic therapy]. AB - Because deep opportunistic mycoses are relatively rare, clinicians frequently lack routine in the application of antimycotics. It is the purpose of this review to summarize, from a practical point of view, rationale, indications, applications and toxicity of antimycotic therapy for the mycoses autochthonous to Europe. Amphotericin B remains the standard therapy for most deep opportunistic mycoses, while the newer azoles are the first line agents to be used for superficial forms of candidiasis. PMID- 2218969 TI - [Current perspectives in ulcer disease]. AB - 1. Helicobacter pylori has been associated with chronic type-B gastritis, which in turn is always present in duodenal ulcer patients; therefore, it is likely that Helicobacter pylori is an important cofactor in the pathogenesis of peptic ulcer disease. An eradication of Helicobacter pylori is associated with the reduced ulcer relapse rate, but an effective therapy for eradication is not yet available and should be restricted to experimental protocols. 2. Omeprazole is an antagonist of the proton pump of the acid-producing cell of the human stomach. With once-daily omeprazole treatment it is possible to almost abolish 24-hour intragastric acidity in the majority of duodenal ulcer patients; therefore, omeprazole allows alternative treatment of different causes of peptic disease. PMID- 2218971 TI - Pericardial effusion after open heart surgery. PMID- 2218970 TI - Role of asbestos and other fibres in the development of diffuse malignant mesothelioma. PMID- 2218972 TI - Trends in lung cancer, chronic obstructive lung disease, and emphysema death rates for England and Wales 1941-85 and their relation to trends in cigarette smoking. AB - Trends in smoking associated respiratory diseases in England and Wales during 1941-85 have been studied, with careful attention to problems caused by changes in classification of cause of death. Three diseases were selected for analysis: lung cancer, emphysema, and chronic obstructive lung disease. During 1971-85 deaths that would previously have been certified under chronic bronchitis have increasingly tended to be classified under chronic airways obstruction. The definition of chronic obstructive lung disease that was used includes both terms to avoid the artificial decline caused by consideration of chronic bronchitis in isolation. Age specific rates for all three diseases show a pronounced cohort (period of birth) pattern, rates for men rising up to the rates for those born shortly after the turn of the century and then declining, and rates for women peaking in the cohort born 20-25 years later. For chronic obstructive lung disease, but not for lung cancer and emphysema, the cohort peak is superimposed on a sharply declining downward trend. In both sexes cohort patterns of cumulative cigarette consumption peak at a time broadly similar to those seen for the three diseases. Trends in cigarette consumption, however, cannot explain the underlying steeply declining rate of chronic obstructive lung disease. Nor can they fully explain the declining trends in lung cancer and emphysema rates in younger men and women. PMID- 2218973 TI - Use of biological glue to control pulmonary air leaks. AB - Biological glue is a natural adhesive generated by the interaction between fibrinogen (pre-glue) and thrombin to produce fibrin. The pre-glue is prepared from a single donor (to avoid the problems of pooled plasma) and stored as cryoprecipitate. Before being used it is thawed, dissolved in saline, and activated into an adhesive by the addition of topical thrombin. Biological glue was used prophylactically to prevent air leaks from bronchial suture lines and raw lung surfaces after pulmonary resections in six patients. In addition two new methods of using biological glue have been developed for the control of persisting air leaks. In selective intrabronchial tamponade the glue is instilled into the bronchial tree through a flexible bronchoscope, and in therapeutic pleurodesis it is instilled into the pleural cavity through a chest drainage tube. The air leaks were resolved in all cases. Seven procedures using selective intrabronchial tamponade were carried out in six patients. Four were immediately successful but three were not and required further interventions. Therapeutic pleurodesis alone was successfully carried out in one patient and as an adjunct to selective intrabronchial tamponade on two occasions. A thoracotomy was eventually needed in one of the seven patients. PMID- 2218974 TI - Effects of inflammation and fibrosis on pulmonary function in diffuse lung fibrosis. AB - To investigate the relation between lung function and inflammation and fibrosis in patients with diffuse lung fibrosis, a study was made of untreated patients without appreciable airway obstruction (14 patients with cryptogenic fibrosing alveolitis and seven with pneumoconiosis). Quantitative assessment of inflammatory infiltration and fibrosis was carried out on open lung biopsy specimens and compared with lung volumes, carbon monoxide transfer factor (TLCO), TLCO corrected for alveolar volume (TLCO/VA), and arterial blood gases at rest and during exercise. The degree of fibrosis and the degree of cellular infiltration were positively correlated. Lung volumes and TLCO were correlated with the grades of fibrosis and cellular infiltration of alveoli; arterial blood gases during exercise tended to correlate with both fibrosis and infiltration (p less than 0.06). In contrast, morphological data were not correlated with gas exchange at rest or with TLCO/VA. It is concluded that, in untreated patients with diffuse lung fibrosis, lung volumes, TLCO, and arterial blood gases during exercise reflect the lung lesions, and that the pulmonary function tests used cannot discriminate between fibrosis and infiltration of the lung by inflammatory cells. PMID- 2218975 TI - Plasma cross linked fibrin degradation products in pulmonary embolism. AB - Plasma concentrations of cross linked fibrin degradation products, a marker of intravascular thrombosis and fibrinolysis, were measured in 495 patients with suspected pulmonary embolism referred for ventilation-perfusion lung scanning to determine whether concentrations are increased in pulmonary embolism and their potential use in diagnosis. Lung scans were described as normal (n = 66) or as showing a low (n = 292), indeterminate (n = 58), or high probability (n = 79) of pulmonary embolism. There was a difference between the mean levels of cross linked fibrin degradation products in each scan category: normal scans, 142 ng/ml; low probability scans, 295 ng/ml; indeterminate probability scans, 510 ng/ml; high probability scans, 952 ng/ml (p less than 0.001). Of the patients with high probability scans, 96% had raised concentrations. Explanations for discrepant low results include incorrect scan diagnosis, delay in blood sampling, and anticoagulation. Of the patients with a low or indeterminate probability of pulmonary embolism, 43% had increased concentrations of cross linked fibrin degradation products that could be attributed in most cases to another illness. Owing to the wide range of values in each lung scan diagnostic category, raised concentrations of these fibrin degradation products cannot be used without reference to the patient's clinical state as a discriminatory test for pulmonary embolism. Further evaluation of the significance of normal concentrations in excluding a diagnosis of pulmonary embolism appears to be warranted. PMID- 2218976 TI - Use of a management plan for treating asthma in an emergency department. AB - A standardised management protocol has been developed for the assessment and treatment of adults with acute asthma attending an emergency department. The management protocol consists of an assessment sheet for recording essential features of the history and examination findings and a flow diagram with guidelines for initial management that were based on spirometric recordings. The protocol was introduced at Wellington Hospital in 1986. The effect of this intervention was assessed by analysing emergency department records during the three months before and one year after the introduction of the protocol. The use of the assessment sheet improved history taking and led to the increased use of serial measures of airflow obstruction and improved documentation of follow up arrangements. The provision of management guidelines influenced the emphasis of management, including an increased use of corticosteroids intravenously and more frequent use of an additional dose of nebulised bronchodilator. In the light of the initial experience the protocol has been modified and its use either in an emergency department or in general practice is recommended. PMID- 2218977 TI - The hyperimmunoglobulinaemia E and recurrent infections syndrome in an adult. AB - A 27 year old white woman with a history of chronic eczema and episodes of serious infection of the chest, skin, and bone presented with acute respiratory failure. She was found to have a spontaneous right pneumothorax and a pneumatocele in the left upper lobe. Despite a left upper lobectomy she was left with chronic respiratory failure, bullous lung disease, and bilateral bronchiectasis. The hyperimmunoglobulinaemia E and recurrent infections syndrome was diagnosed only in adult life. PMID- 2218978 TI - Pulmonary disease following intravesical BCG treatment. AB - Bacillus Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis that has been used in the treatment of malignant disease for over 20 years and for the treatment of bladder cancer since 1976. Major complications of this treatment are infrequent. We report two cases of systemic illness with pulmonary manifestations after treatment with intravesical BCG. PMID- 2218979 TI - Bronchoalveolar lavage findings in a patient with the organic dust toxic syndrome. AB - A previously healthy student developed the organic dust toxic syndrome after unloading a grain silo for one day. Bronchoalveolar lavage seven days later showed a total cell count six times normal with 70% lymphocytes. This suggests that the previously described acute neutrophil influx into the alveolar spaces in this syndrome is rapidly replaced by a lymphocyte dominated infiltration. PMID- 2218981 TI - Behavioural breathlessness. PMID- 2218980 TI - Effort rupture of the diaphragm. AB - Effort rupture of the diaphragm is rare and accounts for only 1% of all diaphragmatic injuries. A 23 year old patient with bilateral rupture that followed sudden movement is described. PMID- 2218982 TI - [Quality assessment in hospitals]. PMID- 2218983 TI - [Funding for hip joint surgery]. PMID- 2218984 TI - [Saving blood--what do we use instead?]. PMID- 2218985 TI - [Fluid therapy changes in surgical treatment of abdominal aortic aneurysm]. AB - The use of blood components and blood substitutes was studied in 25 patients undergoing surgical treatment for abdominal aortic aneurysm in 1983, and was compared with the use of such components in 44 patients operated in 1988. The use of blood components had decreased by 49% from 1983 to 1988. In 1988, erythrocytes were administered only when the hemoglobin concentration fell under 9 g/100 ml. The use of plasma postoperatively was reduced to a minimum. Normovolemia was maintained with polygeline, dextran, electrolytes and autotransfusion. The change in transfusion praxis did not lead to any reduction in postoperative hemoglobin values. The stay in hospital and the number of hours spent in a respirator were both reduced, and there was a general improvement in results. PMID- 2218986 TI - [The Bugoynes study. Population of Finnish ethnic background in Sor-Varanger. IV. A follow-up based on the cardiovascular study done in the county of Finnmark in 1987]. AB - An investigation conducted in 1972 among adult males in the fishing village of Bugoynes, where the majority of the population is of Finnish ethnic background, showed very high serum cholesterol values. This led to a recommendation that the population should modify its dietary habits. 1-1.5 years later the cholesterol values were reduced on average by 17.8%. Part of the adult population was reinvestigated in 1974 and 1977. At the last screening, in 1987, the whole adult population was invited to the investigation. In the age group 20-49 years the age adjusted serum cholesterol values in males were 16.8% lower in 1987 than in 1972. In females in the same age group the values had dropped by 5.4% from 1974 to 1987. Compared with neighbouring villages, the population in Bugoynes has changed its dietary habits. The prevalence of atherosclerotic heart disease in males aged 40-59 years, has declined from 18.9% in 1972 to 8.3% in 1987. PMID- 2218987 TI - [Accidental poisoning in children]. AB - A retrospective study was carried out among children admitted to the Pediatric Clinic, Haukeland Hospital, from 1958 until 1986 for accidental poisoning. Drugs was the most frequent poisoning agent (49%), followed by household agents (22%), different agents (20%) and plants/mushrooms (9%). 89% of the children were under five years of age, 57% were boys. 20% stayed more than one day in the hospital. Very serious poisonings involving admission for more than 14 days were most frequently seen after intake of drugs. The number of admissions was doubled from 1966-70 to 1981-85. Most of the increase referred to poisoning from plants, tobacco and hydrocarbon products. The greatest increase was found for admissions lasting less than two days. Most of the potentially serious poisonings in our study were caused by agents that, by American or British law, it would have been illegal to sell without special child-resistant packaging. It is strongly advised that a similar law be passed in Norway. PMID- 2218989 TI - [Ventricular tachyarrhythmias. Etiology, diagnosis and treatment, based upon a group of patients]. AB - Sustained ventricular tachycardia and ventricular fibrillation are found to be the main causes of sudden cardiac death in out-of-hospital patients. Most of these patients do have serious organic heart disease, hence the arrhythmia must be regarded as a dangerous symptom. Of 44 consecutive patients referred for further investigation of either of these arrhythmias, organic heart disease was found in 43 (98%). Coronary heart disease and cardiomyopathy were the two most common illnesses found. Surgical treatment was efficient in cases of arrhythmias induced by myocardial ischaemia, and even patients with marked reduction in their left ventricular performance tolerated surgery well. As for the medically treated patients, the recurrence rate appeared to be lowest among those who received class-III-antiarrhythmic drugs. PMID- 2218988 TI - [Intracutaneous injections of sterile water as analgesia during labor]. AB - The author points out that when midwives inject sterile water in the lumbar region as a form of analgesia during the first stage of labour, this may prolong delivery. The author has found no documentation to support this method. The labour lasts almost two hours longer in women receiving such injections. There is no adverse effect on Apgar score after one minute. More investigation is necessary in order to examine the effectiveness and/or adverse effects of method. PMID- 2218990 TI - [Percutaneous closure of ductus arteriosus using the umbrella technic]. AB - In four patients between three and five years of age we performed closure of open ductus arteriosus with the Rashkind umbrella technique after percutaneous approach from the right groin. The smallest internal ductus diameter measured between 2 and 4 mm, and pulmonary blood flow was from 1.4 to 2.0 times systemic flow. In all four patients, pulmonary artery pressure was normal. In three patients the ductus arteriosus was completely closed, in the fourth a small residual shunt persisted. There were no complications. We describe the method in detail. PMID- 2218991 TI - [Crossed renal ectopia with nephrolithiasis]. AB - Crossed unfused renal ectopia is an uncommon anomaly in which one of the uretes crosses the midline from the kidney to the vesical orifice on the opposite side. We report one case of crossed unfused renal ectopia, nephrolithiasis and pain on the side opposite to the renal mass. PMID- 2218992 TI - [Blood saving--what do we use instead? Fluid substitution during surgery of abdominal aortic aneurysm]. AB - The use of blood components in major surgery has been reduced significantly. Full agreement exists that patients should be held normovolemic. However, the selection of blood substitutes is controversial. In the present study we analysed infusion and transfusion policy in seven major Norwegian hospitals during and following aortic surgery. The number of patients who underwent surgery for abdominal aortic aneurysm increased significantly from 1983 to 1988. The proportion of emergency operations remained unaltered. We found a significant reduction in the use of blood components. The amount of clear solutions remained unchanged. Two hospitals had chosen polygeline as the main blood substitute, six hospitals preferred dextran 70 as a combined volume substitute and prophylaxis against thrombosis. Two hospitals used albumin 4% as recommended by the blood banks, and four used autotransfusion. Both mortality and morbidity decreased during the five-year period. PMID- 2218993 TI - [Puncture of the joints]. PMID- 2218994 TI - [Hyponatremia. A retrospective study of occurrence, etiology and mortality]. AB - In patients admitted to a general medical ward, the incidence of hyponatremia on admission was 3.6%. Mortality was more than three times higher among patients with hyponatremia than among the patients as a whole. The triad hyponatremia, hypoalbuminemia and hypervolemia indicated a poor prognosis. A diversity of medical illnesses was associated with hyponatremia, and the use of diuretics was a major contributor to the electrolyte disturbance. Treatment of asymptomatic hyponatremia is discussed, with special emphasis on restriction of fluids. PMID- 2218995 TI - [Do antidepressive agents have analgesic effects?]. AB - Patients with chronic pain are often depressed, and antidepressants have been widely used in the treatment of these patients. Well controlled clinical studies have shown that antidepressants have analgesic effects, apparently independent of changes in mood, and in lower doses than used in the treatment of depression. Good results have been reported for several types of chronic pain, especially headache and facial pain, arthritis, fibromyalgia and neuralgias. In addition, antidepressants have also an indirect analgesic action by relieving a depressive condition associated with chronic pain. PMID- 2218996 TI - [Use of economic incentives to promote hip replacement surgery at the regional hospital in Tromso]. AB - Since 1 December 1988, the Norwegian Health Department has refunded NOK 12,000 for each patient operated with a total hip replacement. The intention has been to encourage the hospitals to increase their capacity to operate such patients. The Regional Hospital of Tromso has paid the hospital staff extra to operate patients on Saturdays. In this way 58 extra patients received a total hip replacement in 1989. The cost for each such extra patient was NOK 24,869. In comparison, the regular cost for such patients is NOK 35,125. In our opinion, the hospital has found a simple and economical way to increase its capacity for operating patients with total hip replacement. PMID- 2218997 TI - [Health care and social planning--priorities or wishes?]. AB - The object of this research project was municipal planning of social services and health care. According to the regulations, the planning process shall result in a plan that gives guidelines for further development in the sector. Through data from a representative selection of Norwegian municipalities, it was found that the formulations of the goals in the plans were vague and unprecise. The plans generally include a long list of proposed new initiatives. There is hardly any evidence of choosing priorities or changing priorities. In their present form, the plans are more like lists of open wishes than tools for decision making. They therefore serve to raise problems rather than work as instruments for deciding priorities. PMID- 2218999 TI - [Alcohol abuse as the cause of hospital admissions]. PMID- 2218998 TI - [Who is expert on justice--specialists or the local medical and social observers?]. AB - A young Norwegian father was convicted of having battered his 5 month-old daughter to death. The trial relied heavily on a medicolegal autopsy report, the conclusions of which have been later questioned by clinical specialists. These specialists claim that the child died a natural death from hitherto undiagnosed osteogenesis imperfecta. The correspondence raises the question of why the opinions of local medical instances, and of people who had known the family and the circumstances for a long time, were neglected in favour of the opinions of experts during all phases of the trial. These people were convinced all the time that the child had been weak and sick from birth onwards, and that the innocent father was a victim of the tendency of the courts to accept expert advice only. PMID- 2219000 TI - [Drug induced damage of the nervous system]. PMID- 2219001 TI - [Loss, depression and immunity]. PMID- 2219002 TI - [Health services for immigrants]. PMID- 2219003 TI - [Self-serving waste]. PMID- 2219004 TI - [Is statistical analysis adequate for the evaluation of measuring methods? Lack of information and statistical data]. PMID- 2219005 TI - [Smoking and health attitudes in Norway]. PMID- 2219006 TI - [Electric stimulation of the pelvic floor]. PMID- 2219007 TI - [Osteogenesis imperfecta]. PMID- 2219008 TI - [Autologous bone marrow transplantation in children--experience with neuroblastoma]. AB - Autologous bone marrow transplantation permits the use of greatly intensified cytoreductive therapy for cancer. Since 1983 seven children with disseminated neuroblastoma (stage IV) were treated by this method. Five were treated in first, and one in second complete remission; one child was in partial remission. Tumor cell purging of the marrow inoculum was performed in five cases. All children had engraftment and were discharged from hospital free of disease. Relapse was observed in three children within two years. Four children remain healthy at follow-up 5-77 months after autotransplantation. We describe and discuss indications, methods, side effects and results. PMID- 2219009 TI - [Testing of lung physiology in infants]. AB - We evaluate the clinical value of pulmonary function testing in infants. 194 infants were examined over a period of two years. Pulmonary function testing was found valuable in adjusting the ventilator to avoid overdistension of the lungs in the treatment of severe respiratory distress syndrome. In patients with bronchopulmonary dysplasi, forced expiratory flows were valuable in evaluating the degree of obstruction and for testing drug effects. Both systems used (Pulmonary Evaluation and Diagnostic System (PEDS) and Partial Forced Flow System (PUFFS)) were found to be user friendly. PMID- 2219010 TI - [Bronchopulmonary dysplasia--a general overview]. AB - The article reviews the etiology, pathogenesis and symptoms of bronchopulmonary dysplasia, at present one of the most important complications to prematurity and neonatal lung disease. The different alternatives and aspects of treatment are discussed, with emphasis on the problems of adequate growth and nutrition. PMID- 2219011 TI - [Bronchopulmonary dysplasia--a one-year material]. AB - We report the results of a prospective study on the incidence of bronchopulmonary dysplasia (BPD) in premature infants with gestational age less than or equal to 32 weeks who were treated at Rikshospitalet in 1989. Of a study population of 119 infants, 23 (19.3%) developed BPD. The incidence was 22.5% in the 112 infants who survived the neonatal period. BPD was found only in infants who had been treated with mechanical ventilation for respiratory distress syndrome (RDS). Pulmonary function studies at three days of age demonstrated no significant differences between infants who developed BPD and infants who had RDS only. However, at 12 days of age, no change in compliance and resistance were found in infants who developed BPD, while in infants who only had RDS these lung parameters had markedly improved during this period. PMID- 2219013 TI - [Tricuspid valve endocarditis with pulmonary embolism]. AB - We describe two patients suffering from bacterial endocarditis with tricuspid valve envolvement. Both had pulmonary embolism, revealed by scintigraphic lung perfusion examination. The diagnosis was made by transthoracic echocardiography in one patient and transoesophageal echocardiography in the other. Both received therapy with antibiotics and heparin given intravenously. In one patient the vegetation disappeared. We discuss the epidemiology, diagnosis and treatment of the condition, with special focus on the possible role of heparin. PMID- 2219012 TI - [Portal vein thrombosis. Etiology, complications and therapy]. AB - In a retrospective study of 25 patients with portal vein thrombosis the etiology has been disclosed in 44%. The most common causes were infection, cirrhosis and a myeloproliferative syndrome. The most common mode of presentation was gastrointestinal bleeding (44%). 12 patients (48%) died, the majority after life threatening variceal bleeding. Today we restrict ourselves to treating the complications of portal hypertension. The aim for the future must be to diagnose and dissolve the thrombi shortly after formation. PMID- 2219014 TI - [Localized amyloidosis of the lower respiratory tract]. AB - Primary amyloidosis localised to the lungs can simulate different types of lung diseases such as tuberculosis, carcinoma and repeated infections in the lower respiratory tract. The possibilities of treatment are limited. The prognosis is usually good, except when there is diffuse pulmonary involvement. Such patients can develop progressive respiratory failure The mechanism of amyloidogenesis is unclear. At the cellular level the macrophage may play a central role. PMID- 2219015 TI - [Combined lung and heart surgery]. AB - Patients with concomitant pulmonary carcinoma and serious heart disease represent a therapeutic challenge. With the introduction of combined lung-heart surgery, both conditions may be treated adequately and safely. At Rikshospitalet, combined surgery was performed in four cases during the period 1984-88. In three patients heart surgery and lung resection were performed in one anesthetic session. In the fourth case the heart disease was corrected first and the tumor removed a few weeks later. After 1-4 years follow-up none of the patients has clinical manifestations of either condition. Combined surgery is only applicable if tumor removal is confined to wedge resection or lobectomy. PMID- 2219016 TI - [Sulindac-induced toxic epidermal necrolysis]. AB - All nonsteroidal anti-inflammatory agents may have dermatological side effects, most of them harmless. However, serious adverse dermatological reactions have been described. The article presents a patient with probable sulindac-induced toxic epidermal necrolysis (TEN), and reviews the literature. PMID- 2219017 TI - [Routine control of type 2 diabetes. Are glycosylated hemoglobin and fructosamine measurements necessary?]. AB - In 98 type 2-diabetics with stable fasting blood glucose who were treated by tablets and/or diet, fasting blood glucose, glycosylated hemoglobin A1c and serum fructosamine were measured simultaneously. Fasting blood glucose was defined as stable when all values were less than 7.1 mmol/l, or deviated by less than 20% in at least three months, and the treatment had not been changed during the last six months. There is satisfactory correlation between fasting blood glucose and glycosylated hemoglobin A1c (r = 0.64), and serum fructosamine (r = 0.63). It is concluded that glycosylated hemoglobin and fructosamine are superfluous in routine controls of such patients. When fasting blood glucose is unsuitable for practical reasons, fructosamine is a good and cheap alternative. In annual controls glycosylated hemoglobin is the best parameter, and reflects the longest period of metabolic control. PMID- 2219018 TI - [Testicular germ cell tumors--epidemiology and risk factors]. AB - An increasing incidence of testicular germ cell tumours has been observed in many white populations in this century. Ethnic genetic implications and lifestyle seem to influence the development of testicular cancers, whereas the influence of intrauterine conditions is under debate. Epidemiologic studies cannot explain the increasing incidence among young men. The age variation of incidence and histologic type indicates at least two different aetiological mechanisms. Testicular cancers among young men are most probably due to gonadal dysgenesis, whereas in old men they reflect the general increased risk of cancer with old age. The increased risk of developing testicular germ cell tumours among cryptorchid young men supports the gonadal dysgenesy hypothesis. PMID- 2219019 TI - [The science of the art of medicine. Qualitative methods in medical research]. AB - Qualitative research methods dominate in the humanities (history, literature), theology, law and some social sciences (ethnography). The authors claim that using such research traditions could expand the scientific field of medical research, and that qualitative methods can be tools for medical scientists to gain knowledge of matters that until now have been obscure. This article presents some characteristics of these research traditions: Qualitative researchers tend more often to formulate questions and hypotheses than provide answers. They produce arguments for a given result, and do not pretend to prove facts. The qualitative researcher works mainly with texts (documents, transcriptions of interviews etc.) not with numbers and statistics. The article presents a survey of qualitative research methods, and gives examples of the use of these methods in medical research in general practice. Finally the authors discuss the problems connected to using the concept of "science" in everyday medical practice. PMID- 2219020 TI - [Allergic reactions during streptokinase therapy]. AB - The article reviews immunological reactions to streptokinase. The humoral immune response to streptokinase involves antibodies of different subclasses, including IgG, IgM, and IgE. A T cell response to streptokinase can also be demonstrated, involving both CD4 and CD8 positive cells. Streptokinase therapy involves increased risk of all kinds of allergic reactions, including urticaria, bronchial obstruction, shock and serum sickness. PMID- 2219021 TI - [Intravenous drug users and contact with the health care system]. AB - Intravenous drug users in the Oslo area seem to have rather limited contact with treatment programmes (outpatient or inpatient). The data are taken from a survey of intravenous drug use among arrestees at Oslo Central Police Station. 1,394 intravenous drug users were examined. Less than one third reported having had any contact with a treatment programme during the last six months, and less than 50% reported such contact during the last two years. More than 50% said that they had never been admitted to an inpatient treatment institution. PMID- 2219022 TI - [Accomplish more for less--a status report from Lovisenberg hospital]. AB - In 1988 the local authorities increased the catchment area and reduced the budget for Lovisenberg hospital in Oslo. The hospital has met this challenge by improving its productivity. Despite a 20% cut in the acute bed capacity, the number of discharged patients was increased by 19 and 16%, and the length of stay for hospital care was shortened by 33 and 26%, at the medical and surgical departments respectively. The shorter period of hospitalization did not affect mortality or frequency of readmissions. We conclude that the present budget cuts have led to valuable changes at our hospital. The number of acute beds is now well balanced with the size of the catchment area (2.5 beds per 1000 inhabitants). However, further reduction is not advisable. PMID- 2219023 TI - [Heredity and colorectal cancer]. PMID- 2219024 TI - [Improved treatment of aortic aneurysms]. PMID- 2219025 TI - [Are streptococcal infections on the rise?]. PMID- 2219026 TI - [Diseases caused by Streptococcus pyogenes in Norway, 1975-1989. A microbiologic and epidemiologic survey]. AB - The article briefly surveys the epidemiology of Streptococcus pyogenes caused disease in Norway during the last 15 years based on notification data, with emphasis on the nation-wide outbreak in 1987-88 caused by mucoid M-1 organisms. During the season S. pyogenes infections was 60% higher than expected. The number of bacteraemia cases, many with fulminant septicaemia, showed an almost threefold increase compared with earlier years. Unusual clinical manifestations such as necrotising fasciitis, pneumonia with empyema, primary peritonitis and meningitis also occurred. We briefly review the known virulence factors of S. pyogenes in an attempt to improve our understanding of the shift in clinical manifestations and occurrence of the disease. PMID- 2219028 TI - [The challenges of differential diagnosis of infections caused by beta-hemolytic streptococci]. AB - Infections due to Streptococcus pyogenes are varied and often difficult to diagnose. During the last few years the clinical manifestations of these infections and the treatment rationale have changed. New diagnostic tests have been introduced. The present article reviews the diagnostic possibilities based upon clinical findings, the doctor's own laboratory and the microbiological laboratory. Rapid immunological tests, differential leukocyte count and C reactive protein are pointed out as potentially useful laboratory tools for the clinician. PMID- 2219027 TI - [Clinical manifestations caused by group A streptococci]. AB - We describe the symptomatology of different disease entities caused by group A beta-hemolytic streptococci (Streptococcus pyogenes, GAS). The case histories of four patients, two of whom died, emphasize the severity of certain clinical manifestations of GAS-infections. A 34 year-old woman was admitted to hospital four days after start of the symptoms. She presented a clinical picture very similar to that observed in fulminant meningococcal septicaemia; i.e. extensive skin haemorrhages, circulatory collapse, and multiple organ failure. She died within 12 hours of admission. GAS were isolated in blood culture. A seven day-old girl died before admission to hospital. GAS were isolated in blood cultures, cerebrospinal fluid and from her nose and throat. An eight year-old, psychomotoric retarded girl developed a severe left-sided pneumonia, empyema and scarlatina. GAS were detected in throat culture. She responded poorly to high doses of benzylpenicillin given intravenously. She recovered rapidly after thoracotomy and decortication of her left lung. Finally, we describe the case of an 11 year-old boy with rheumatic fever without cardiac involvement. The reported cases underline the need for careful diagnosis and penicillin treatment in cases of GAS-infections. PMID- 2219029 TI - [Necrotizing fasciitis caused by group A streptococci]. AB - The number of serious infections from group A streptococci has increased, and there have simultaneously been several cases of necrotizing fasciitis. This is an uncommon, but well-defined entity characterized by extensive necrosis of subcutaneous tissue and fascia, combined with signs of septicaemia. It is often accompanied by multi-organ failure. The mainstay of management is early diagnosis and prompt surgical intervention. It is mandatory that a surgeon, an infectious disease specialist and an anaesthesiologist collaborate on the therapy as a whole. PMID- 2219030 TI - [Improved treatment of abdominal aortic aneurysms. Progress over 17 years]. AB - During the period 1970-86, 155 men and 24 women were operated on for abdominal aortic aneurysms at the University Hospital in Tromso. Elective operations were performed in 76 patients with an operative mortality of 5 (7%), impending rupture in 49, of whom 14 died (29%) and ruptured aneurysms in 54 patients, of whom 33 (61%) died. There has been a substantial increase in the number of patients per year admitted with abdominal aneurysms, from an average of 4.5 during the years 1970-76 inclusive, to over 20 during the years 1984-86. Operative and early postoperative mortality have been reduced and there has been no death following elective operations during the last three years of the reported period. Mortality was 8% for impending rupture and 45% for ruptured aneurysms. Electively abdominal aortic aneurysms can be operated safely even in patients over the age of 80. Ruptured aneurysms, however, still carry a high operative mortality in patients over the age of 70. PMID- 2219031 TI - [Outpatient angiography]. AB - During the last few years it has been generally accepted that angiography can be performed on an outpatient basis. In 1988 and 1989, 130 angiographies were done in this manner at the Regional Hospital in Trondheim. All the examinations were carried out by conventional transfemoral technique. After the procedure the patients were observed for six hours in the surgical ward of the hospital before going home. 25 patients had to be hospitalized after examination. Only in two cases this was due to minor complications of the angiography. None of the patients experienced complications after discharge from hospital. The conclusion is that outpatient angiography must be considered a safe and cost-effective procedure. PMID- 2219032 TI - [Central nervous symptoms and findings in patients with systemic lupus erythematosus]. AB - Systemic lupus erythematosus is a disease characterized by multiple autoimmune phenomena, and a broad clinical spectrum. Involvement of the central nervous system is common, and in the majority of patients occurs mainly as an organic brain syndrome or as migraineous headache. Cerebral atrophy as judged by CT scan is common. Cerebral infarction occurs in a minority of patients, mainly those with high disease activity and a high titer of anti-phospholipid antibodies. Systemic lupus erythematosus should be considered as a possible diagnosis in patients with certain central nervous system aberrations, especially young females. PMID- 2219033 TI - [Neuromuscular symptoms and findings in systemic lupus erythematosus]. AB - Systemic lupus erythematosus (SLE) gives rise to a variety of autoimmune and clinical phenomena in a multisystem manner. Both the central and peripheral nervous systems are involved as well as skeletal muscle. Based on our work with SLE patients, we describe the different categories of peripheral neuropathy and myopathy. We suggest that the disease be considered as a possible diagnosis, especially when evaluating women with symptoms and signs of neuromuscular abnormalities. PMID- 2219034 TI - [Idiopathic long QT syndrome. An underdiagnosed disease]. AB - Two eleven-year old boys were referred to the medical department, division of cardiology, Aust-Agder Central Hospital, because of reported attacks of syncope during physical exercise. Idiopathic prolongation of the QT-interval was diagnosed and their families were examined. A total of 25 patients with long QT syndrome were identified. Eight patients had attacks of syncope, six patients had dizzy spells and five persons were asymptomatic. Nine cases of sudden and unexpected death were assumed retrospectively to be due to QT-prolongation. All patients with syncopes of unknown cause should be examined for QT-prolongation, and the study confirms the importance of examining all family members of patients with idiopathic long QT-syndrome. PMID- 2219035 TI - [Rehabilitation after stroke]. AB - Our hospital's stroke rehabilitation programme has been evaluated through a retrospective study of the record of 183 males (mean age 60 +/- 11 years) and 94 females (mean age 59 +/- 14 years) admitted in 1982/83. 87% of the patients had motoric impairments on admission; 45% had apraxia, 17% neglect, 38% aphasia and 57% other cognitive impairments. Most patients had both motoric and cognitive problems. 79% were able to ambulate freely at discharge as opposed to 55% on admission. 88% were independent in ADL when discharged; 67% on admission. The average length of stay (LOS) was shorter (p less than 0.005) for the males (57 +/ 32 days) than for the females (68 +/- 40 days). LOS was not significantly influenced by the patients' age. 81% of the patients were discharged to their homes. Significantly fewer patients with cognitive impairments were able to return to their homes after rehabilitation than in the case of those without such problems. The presence of aphasia did not significantly affect the rehabilitation outcome. It is concluded that the major obstacles for successful rehabilitation (i.e. back to the patient's home) are the cognitive impairments. PMID- 2219036 TI - [The risk of exposure to hepatitis B and human immunodeficiency virus among employees at Norwegian hospitals]. AB - During the period from 1986 to 1989 a study was carried out to determine the risk of occupational exposure to hepatitis B virus and human immunodeficiency virus among approximately 5,500 employees at Aker hospital, Ulleval hospital and "Sentralsykehuset" in Akershus. Four hundred and fourteen injuries were reported during the study period of approximately 16,800 man-years, corresponding to an injury rate of 2.4/100 man-years. The majority of injuries occurred during direct patient contact in the wards. Of the known sources 8.2% were HBsAg positive and 16.8% HIV-antibody positive. One attendant contracted hepatitis B during the observation period. No HIV-seroconversion has been observed as yet. PMID- 2219037 TI - [Ocular prosthesis production in Norway]. AB - Individually adapted acrylic ocular prostheses are presented as an alternative to glass prostheses, which up to now have been the technique available to Norwegian patients who have lost an eye. The article describes the technique used to produce acrylic eyes and sums up the advantages of acrylic eyes compared with prostheses of glass. PMID- 2219038 TI - [Punch biopsy]. PMID- 2219039 TI - [A neurologic day care clinic. Presentation of the concept, and the first 271 patients]. AB - Most of the patients remitted to this service are former inpatients who need more comprehensive examinations than usually performed in an ordinary outpatient setting. They attend for one or more days during office hours, spending the night at home or in a hotel. Investigative procedures are ordered in advance, and the patients receive written information about the various tests beforehand. Of the first 271 patients, 206 attended for one day, 63 for two days and two for three days. The examinations comprised 81 by lumbar myeloradiculography, 59 EMG, 56 EEG, 46 cerebral CT scan, 33 SER (somatosensory evoked response), 32 BAER (brainstem auditory evoked response), and 16 VER (visual evoked response). A spinal fluid tap was performed in 49 patients, muscle biopsy in five patients, and 51 were examined by doppler of the precerebral arteries. The fact that the patients attend for one or more days instead of one hour is also of great benefit for teaching and research purposes. PMID- 2219040 TI - [Multidisciplinary assistance in a case of conduct disorder. A three-year project]. AB - Conduct disorders are common. They concern many people inside and outside the health service. They are often a cause of despair in individuals, in the family and among professionals. This article describes the situation of a young boy. In 1985 everybody was about to give up and said there was nothing more that could be done for him. In this situation a municipal multidisciplinary team, with a three year programme of treatment was organized. The purpose was to find out if it was possible to create new meanings in his surroundings, to give him a new start. The result is promising. PMID- 2219041 TI - [Use of public health statistics in the development of community diagnosis]. AB - A community diagnosis which describes the health of the local population may be an important instrument in promoting health and preventing disease. Most general practitioners do not have time to carry out individual surveys in the local community. Therefore it seems relevant to look into the possibility of utilizing official health statistics as a basis for community diagnosis. We obtained and analysed demographic data, mortality data, statistics on cancer, data on causes of invalidity and risk factors for cardiovascular diseases for Askvoll municipality. This article demonstrates possibilities, obstacles and constraints in the use of such statistics. Suppliers of register data should make routine health statistics more available for use in the district health services. In this connection we recommend the development of a central health data information system. PMID- 2219042 TI - [Counselling in unplanned pregnancies]. AB - The article describes experiences in a family guidance clinic when counselling women in early pregnancy. The women voluntarily sought help in deciding whether to have a legal abortion or to have the child. In this setting we have focussed mainly on the emotional relationship between the partners, and on the psychological reactions of the women confronted with this difficult choice. PMID- 2219043 TI - [Smoking and attitudes in Norway]. PMID- 2219044 TI - [Latent and activated viral infections]. PMID- 2219045 TI - [Should research be done at peripheral hospitals?]. PMID- 2219046 TI - [Acute respiratory distress syndrome in adults]. PMID- 2219047 TI - [Acute pulmonary dysfunction in adults. Adult respiratory distress syndrome- ARDS]. AB - During a 3-year period 0.1% of all patients undergoing surgery and 0.3% of the patients submitted for trauma developed ARDS. The diagnosis was based on strict criteria. Mortality among the 42 patients was 45.2%. Abdominal sepsis was associated with high mortality, trauma with a much better prognosis. Swan-Ganz catheters were used in 81% of the patients. The measurements were characterized by high pulmonary vascular resistance and increased intrapulmonary shunting. However, the initial recordings showed only small differences between survivors and fatal cases as regards haemodynamics and blood gas parameters. Mortality was associated with low diuresis, heart failure, need of inotropic support and on age of over 50 years. The significance of invasive central monitoring is discussed. PMID- 2219048 TI - [Lung shock in connection with acute myocardial infarction. Adult respiratory distress syndrome, ARDS]. AB - We describe the case of 42 year-old male patient who developed adult respiratory distress syndrome (ARDS) during an acute myocardial infarction. He was treated with positive pressure ventilation for 23 days. Chest X-ray showed multiple, bilateral infiltrates for several weeks. ARDS is accompanied by serious and progressive hypoxemia. Early diagnosis is important. The therapeutic consequences involve positive pressure ventilation with increased inspired oxygen concentration and positive end-expiratory pressure. ARDS in patients with impaired myocardial function can be difficult to recognize. It is an alternative diagnosis to pneumonia and ordinary heart failure when patients are seen to be suffering serious hypoxemia. PMID- 2219050 TI - [Xanthogranulomatous pyelonephritis. A benign, solid kidney tumor]. AB - We report the case of a 68 year-old woman who underwent surgical treatment for xanthogranulomatous pyelonephritis. Xanthogranulomatous pyelonephritis is a rare, chronic, inflammatory lesion of the kidney. It is most frequently seen in middle aged women. Because of its clinical and radiological similarities to other renal lesions it can be difficult to establish a preoperative diagnosis. Nephrectomy is needed in most patients. PMID- 2219049 TI - [A phase II study of 5-fluorouracil/cisplatin in recurrent cervical cancer]. AB - 50 patients with recurrent cervical carcinoma were included in a phase II study of cisplatinum and 5-fluorouracil. They were divided into patients with recurrent lesions outside the previously irradiated area (group 1) and those with at least one recurrent lesion inside this area (group 2). The treatment schedule consisted of 5-fluorouracil 1,000 mg/m2 intravenously during days 1 to 5, and cisplatinum 100 mg/m2 intravenously in day 1. 45 patients could be evaluated for response and toxicity with a median survival of 14+ months, (range 4-38+). In group 1 (29 patients) seven achieved complete response with a median duration of 14+ months, (range 3(+)-26+), median survival of 19+ months, (range 5(+)-28+), and 13 achieved partial response with a median duration of 8+ months, (range 3(+)-25+), median survival of 16 months, (range 6(+)-31+). In group 2 (16 patients) one patient achieved complete response and two partial response. One patient in this group with stationary disease is still alive after 38+ months. All the patients suffered from nausea and vomiting. The dose-limiting factor was bone marrow suppression. The response rate in group 1 of 69%, with a median survival of 19+ months, is higher than previously achieved with other cytostatic regimens. We found the regimen to be very toxic, however, for patients with central recurrences in previously irradiated areas, though some of these patients did achieve marked relief from pain. PMID- 2219051 TI - [Viral infections in immunocompromised patients]. AB - An increasing number of patients are immunocompromised due to modern treatment of cancer, organ transplantations and HIV-infections. Opportunistic viral infections are common and may cause serious disease among these patients. New vaccines, immunomodulators and antiviral drugs make it possible to prevent and treat many of these infections. We review the host defence against viral infections and the most important viral infections. We also discuss prophylaxis, diagnosis and therapy. PMID- 2219052 TI - [Correlation of symptoms and clinical findings in polyneuropathy]. AB - A scoring system for neuropathic symptoms (neuropathic symptom score) and signs (neurologic disability score) has been applied on 30 patients with polyneuropathy. Vibration sense thresholds were also measured by vibrametry. A statistically significant association between the neuropathic symptom score and the neurologic disability score was demonstrated. Disability scores expressing sensory items were significantly associated with vibration threshold on the index finger and even stronger with that on the big toe, which also correlated well with the sum of the patients' neuropathy deficits (total neurologic disability score). We recommend that registration of neurologic disability score in particular and if possible also vibrametry (and other quantitative sensory tests) are performed in the primary evaluation of patients with polyneuropathy, and especially in subsequent examinations to clinically monitor the patients. PMID- 2219053 TI - [The examination pattern at an x-ray department over a 25 year period]. AB - The pattern of examinations at the x-ray department of Buskerud sentralsykehus has changed over the last 25 years. Heart- lung- and skeleton examinations remain unchanged, and represent 71 to 79% of the total number, but there has been a marked charge in other examinations. Through the years there has been a marked decline in the number of "classical" contrast medium examinations of gallbladder/gall-paths, gastroduodenal examinations and intravenous pyelography. Air-encephalography has disappeared, and arthrography is about to disappear as an x-ray examination. New methods, such as computer-tomography and ultrasonography and non-radiological examinations, such as gastroscopy and arthroscopy, seem to be the main reason for this change, but other factors, such as change in disease patterns and therapeutic procedures may also have contributed. PMID- 2219056 TI - [Clinical research--relations of central and peripheral hospitals]. AB - Clinical research is of great importance for the patients, the medical industry, doctors, hospitals and society as a whole. More time should be set aside for clinical research during (daily) working hours. Arrangements should be made to stimulate and guide young colleagues who have new ideas, through scientific projects at whatever hospital they work. Depending on economy and the doctors' qualifications, central and peripheral hospitals should cooperate on clinical research. Although their hospitals are of different size, the doctors are equally capable and cooperation is characterized by colleagual interdependence. PMID- 2219055 TI - [The loose-leaf book of procedures. A regional model for diagnostic and referral routines--a basis for improved cooperation between primary and secondary services]. AB - Initiated by the Telemark branch of the Norwegian Medical Association a loose leaf book of procedures has been prepared for use in the region of Telemark Central Hospital. The professional advice given in the book is based on an agreement between the chief physicians of the various hospital units, their discussions in the unit, and a group of four general physicians. The advice is only intended as a guide. The editors' idea is to have the book distributed to all G.P.s and hospital units in Telemark. The book is meant to be updated once a year. PMID- 2219054 TI - [Measurement of ankle blood pressure in peripheral atherosclerosis]. PMID- 2219057 TI - [Should we perform long-term cohort studies on the use of antihypertensive agents?]. AB - The 1-year PMS Carduran study included more than 4,500 hypertensive patients treated by more than 600 general practitioners. The objective was to study side effects and treatment efficiency. The Research Board of General Practitioners has criticised this and similar PMS studies because they tend to serve marketing purposes and are of low scientific value. It is argued in this paper that large independent prospective pharmaco-epidemiological studies, if well performed, may provide important information on the use (and possibly misuse) of new drugs in general practice, information which may not be known prior to registration. Also, the great potential in providing long term information on disease prognosis is underlined. An example of a 5-year study of Carduran-treated hypertensive patients is outlined. PMID- 2219058 TI - [Ergotamine induced ischemia]. PMID- 2219059 TI - [Health problems and health care needs of HIV positive drug abusers]. PMID- 2219060 TI - [Atopic dermatitis (eczema) and skin tests]. PMID- 2219061 TI - [Therapeutic and health care needs of HIV positive drug abusers. A study from an emergency institution]. AB - Drug taking behaviour(DTES), psychiatric condition(DSM-III-R) and physical health were evaluated in 44 HIV-positive inpatients at a detoxification unit for drug addicts during the period October 1987 to December 1988. The investigation revealed marked psychopathology, especially in terms of personality disorders. The patients were followed up at the end of April 1989. At this time ten patients were abstinent, though all of them remained under care. 26 patients had relapsed to heavy abuse. Four had died. An unfavourable outcome seems to correlate with heavy abuse and poor physical health. We discuss the consequences for existing provisions for treatment, as well as alternative solutions. PMID- 2219062 TI - [Skin-prick tests in atopic dermatitis]. AB - The usefulness of skin prick tests in the management of atopic dermatitis is discussed on the basis of results from testing 100 patients, mean age 23 years. Skin prick tests may be useful when allergies to food are suspected, and also when it is suspected that the dermatitis is aggravated due to reactions to airborne allergens. Testing with a series of common inhalant allergens may provide information about the tendency to respond with IgE-synthesis. From a practical and economical point of view, a skin prick test may be a good alternative to other techniques for allergy testing. PMID- 2219063 TI - [Alternative medicine and chronic skin disease. Use of alternative treatments among patients with atopic eczema and psoriasis]. AB - In a questionnaire study at a university hospital in Norway, 227 of 444 patients with atopic dermatitis (51.1%) and 215 of 506 patients with psoriasis (42.5%) reported previous or current use of one or more form of alternative medicine. Most used were homoeopathy, health food preparations and herbal remedies. The use was related to the disease duration and severity of the disease and, among the atopic dermatitis patients, lack of effective treatment by physicians, as judged by the patients. The patients also reported on their motivation for alternative medicine, their source of information on such, and its effect. The use of alternative medicine is commonplace and should be of concern to all physicians. The study emphasizes the need for documentation of the effects of alternative therapies. PMID- 2219064 TI - [Blood pressure elevation among industrial workers exposed to stress]. AB - A standardized, annual medical examination of a group of heat workers exposed to, and another group not exposed to heat in a Norwegian ferro-alloy plant over a period of six years showed no statistically significant difference in blood pressure between the two groups. However, following three years of stable blood pressure and heart rates, both parameters increased markedly in both groups. The occurrence of this sudden increase in blood pressure coincided with the plant being threatened with the possibility of closure due to inability to operate at a profit. This threat persisted for more than two years, but even afterwards, when it was quite clear that jobs at the plant were no longer threatened, the blood pressure remained markedly elevated. These findings emphasize the importance of being aware of the possible relationship between prolonged mental stress and hypertension. PMID- 2219065 TI - [The use of copper and niobium filters in diagnostic x-ray equipment. A comparison of dose reduction, tube loading and picture quality]. AB - A dose-reducing niobium filter for use in diagnostic radiology was introduced in Norway in 1989. The effect of this filter was compared with that of an ordinary copper filter. Either a 0.05 mm niobium filter or a 0.10 mm copper filter was placed into the beam from an X-ray tube. Parallel measurements were made of dose reduction to the patient, image quality and tube loading. The copper filter reduced skin doses more than the niobium filter did, and caused less increase in tube loading. The resulting image quality was considered to be the same. We conclude that a 0.10 mm copper filter is better than a niobium filter in achieving a considerable dose reduction to the patient, and is far less expensive. PMID- 2219066 TI - [Wegener's granulomatosis. New aspects of diagnosis, treatment and prognosis]. AB - In its classical form, Wegener's granulomatosis (WG) is characterized by acute granulomatous vasculitis of the upper and lower respiratory tract together with glomerulonephritis, and when untreated, mortality is high. The use of cyclophosphamide and prednisolon has improved the prognosis dramatically, while azathioprine and trimetoprim-sulfamethoxazole are of limited therapeutic value in these patients. Only 1/3 of subacute and chronic cases show renal impairment, and the prognosis is better in limited Wegener's granulomatosis without renal disease than in the classical form. This case-report and review takes up various new aspects of diagnosis, treatment and prognosis. PMID- 2219067 TI - [Yellow nail syndrome. Lymphatic vessel hypoplasia as a cause of pleural effusion]. AB - Yellow nail syndrome is a clinical entity characterized by lymphedema, nail dystrophy and exudative pleural effusion. The cause of the syndrome is thought to be hypoplasia of the lymphatic vessels, with local infection or inflammation as a common precipitating event. Treatment is symptomatic: chemical or surgical induced pleurodesis is the best way of controlling symptomatic pleural effusion. PMID- 2219068 TI - [Diagnosis of type 2 diabetes in general practice]. AB - Among 285 patients seen in general practice, all over the age of 40, 11 (4%) new cases of non-insulin-dependent diabetes mellitus was diagnosed. 12 patients (4%) were found to have impaired glucose tolerance. Measurement of glucose levels in unstandardized blood samples is a suitable method of screening for non-insulin dependent diabetes in general practice. In order to reduce the number of oral glucose tolerance tests we suggest a modification of WHO guidelines. PMID- 2219069 TI - [Institutionalized treatment of agoraphobia with panic anxiety]. AB - We describe an integrated behavioral-psychodynamic treatment programme for inpatients suffering from agoraphobia and panic anxiety. This programme emphasizes intensive drug-free exposure training followed by work with anxiety laden dynamic conflicts. We present promising results of evaluation studies, and discuss the important role of cognitive reconstruction of anxiety and of passive and active avoidant attitudes in exposure training. Lastly, we make certain recommendations concerning the approach to anxiety problems in general practice. PMID- 2219070 TI - [History of the Norwegian Military Medical Association]. AB - The Norwegian Military Medical Association was founded in 1882 by a small group of army doctors. The principal aim of the Association was to establish a structured military medical corps with command functions. Furthermore, the newly founded group of active military doctors was intended to develop the medical knowledge and skills unique to this branch of medicine. In 1888 a military medical organization and command structure was finally accepted. The Association was very active for the first 25 years, printing articles and giving lectures on military medical subjects. After World War II the military medical service was organized in "HQ Defence Command Norway, Joint Medical Service". For many years to come this new organization took over some of the functions of the Military Medical Association. In 1952 the Association was accepted as a special branch of the Norwegian Medical Association. The Norwegian Military Medical Association is now active again, both as an organization and professionally. The number of members is increasing, and includes military doctors in active service as well as civilian doctors with an interest in military medicine. PMID- 2219071 TI - [Treatment of heart failure with angiotensin converting enzyme inhibitors]. AB - Stimulation of the renin angiotensin system, catecholamines and antidiuretic hormone causes prominent vasoconstriction in severe heart failure. Angiotensin converting enzyme inhibitors reverse these effects, and thus ameliorate cardiac function and reduce mortality in severe heart failure. Angiotensin II is an important regulator of renal function in diseases with renal hypoperfusion, and treatment with angiotensin converting enzyme inhibitors may cause a serious decrease in glomerular filtration and hyperkalemia. Asymptomatic heart failure, acute heart failure and acute myocardial infarction are areas where angiotensin converting enzyme inhibitors may prove beneficial in the future. PMID- 2219072 TI - [Diagnostic prick tests]. PMID- 2219074 TI - [Mad cow disease]. PMID- 2219073 TI - [The physician, the drug abuser and drug abuse]. AB - Drug abusers have a low tolerance for unpleasant and painful emotions and experience a need for chemical relief through use of narcotics, tranquilizers and analgesics. Physicians may show a tendency to comply with their request for such drugs, partly because they give way under pressure (threats, violence) and partly because of their own unconscious need for acceptance and appreciation from the patients. The use of prescribed drugs may inspire an illusion that drug therapy is a "solution" and withdraw attention from other therapies. The prescription of medicaments may represent an extension of already existing abuse. Physicians must be aware of these problems of prescription and of the problems connected to patients' use of threats and violence. PMID- 2219075 TI - [Intracutaneous injections with sterile water as obstetric analgesia]. PMID- 2219076 TI - [Toxicological and pharmacological effects of the use of bovine somatotropin in dairy farming]. AB - Some possible toxicological and pharmacological consequences of the use of bovine growth hormone (BST) synthesised using recombinant DNA techniques are discussed in the present paper. Three spheres of interest are reviewed. Target species: When BST is used correctly, negative effects on the target species are unlikely to occur. Obscurity may to some extent remain as regards the effect of BST on the immune system. Residues of BST and IGF: There is nothing to suggest that the BST levels in the milk will increase significantly following BST treatment. Slight elevations of the levels of IGF-1 (one of the so-called somatomedins) in the milk following treatment with BST have been reported. However, the concentration of IGF-1 that is reached after the correct use of BST is still lower than that in milk collected during early stages of lactation. As a result of the peptide character of BST and IGF-1, absorption by healthy human individuals is unlikely to occur. The relevance of the problem of BST and/or IGF-1, absorption from milk by some individuals such as young infants is also discussed in this paper. Interaction with the metabolism of drugs: A possible interaction between BST and drugs which are administered to the animal at the same time, as is observed in rats and occasionally also in human subjects could have consequences for the clinical effectiveness, side-effects and drug residues in food products of animal origin. So far, however, an interaction of this type could not be detected in ruminants. At the present time, this phenomenon is being studied in greater detail.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2219077 TI - [Cobalt deficiency and photosensitivity in a flock of Texel lambs]. AB - In a flock of thirty lambs ten animals showed symptoms of photosensitisation within a short period of time. Soon after treatment with vitamin B12 the symptoms disappeared. Clinical examination, differential diagnosis, treatment and course of the disease are discussed. It is assumed that the lambs suffered from 'white liver disease'. PMID- 2219078 TI - [Endoscopy in gastrointestinal problems in dogs--an indispensable diagnostic technique]. PMID- 2219079 TI - [Malignant grass-tetanus and meat inspection]. PMID- 2219080 TI - [Veterinary Chief Inspection of Public Health. Sequelae of open borders for the veterinary control of food of animal origin]. PMID- 2219082 TI - [Current possibilities of improving health and welfare status of pigs through introduction of the specific 'Stress Free' (SSF) System]. AB - Health and welfare problems of pigs in intensive husbandry systems are mainly caused by housing and management of the animals. The actual structure of these systems also gives rise to health and welfare problems. Solving these problems is very difficult to achieve in the existing systems. It will be necessary to create new structures and housing systems from a preventive veterinary point of view to avoid harm to health and welfare caused by specific stressors. Specific stressors which can be prevented are associated with the risk of infection, mixing and replacing animals, high density, inadequate house climate, handling of animals and the farmer's attitude towards his animals. The SSF-system specifies the method by which these specific stressors are prevented. PMID- 2219081 TI - [Oxytetracycline and oral herd treatment: a literature review]. AB - Pharmacotherapeutic, pharmacodynamic and pharmacokinetic aspects of oral mass medication with oxytetracycline (OTC) in pigs, calves and poultry are discussed in this review. Clinical studies with successful therapeutic results are scarce in literature; however, OTC is still frequently used for mass medication. Some practical advice to improve the bioavailability of OTC is given. This mainly concerns the reduction of the interaction between calcium ions and OTC. OTC may be useful for oral mass medication when applied as a prophylactic drug. Pharmacological studies are required in order to provide more knowledge about the efficacy of OTC-mass medication. Additional information can be acquired from the field by improving and extending the reciprocal co-operation between field veterinarians and diagnostic laboratories. This may lead to a more justified choice from the various possibilities of antimicrobial use in livestock. PMID- 2219083 TI - [Euthanasia of bullfrogs (rana catesbeiana)]. PMID- 2219084 TI - [Vaccination during corticosteroid therapy?]. PMID- 2219085 TI - [Euthanasia of (bull)frogs]. PMID- 2219086 TI - [Veterinary Chief Inspection of Public Health. Salmonella enteritidis in poultry: monitoring and control]. PMID- 2219088 TI - [Lead poisoning in cattle in north Netherlands. October 1989-January 1990]. AB - By the end of 1989 a serious lead intoxication of cattle occurred in the northern part of the Netherlands (provinces Groningen and Friesland). This intoxication appeared to be caused by contaminated feed. Over 300 farms were stricken, with about 15,500 animals (mostly dairy cattle). In a period of one to four weeks these animals consumed about 1,000 kg of lead. This resulted in lead levels in milk, livers, and kidneys above the regulatory safety limits. Thanks to the chelating therapy that was rapidly applied by the local veterinarians, only about 30 animals died of an acute lead intoxication. The cooperating governmental and private authorities took action to prevent exposure of consumers to lead contaminated animal products. Based on careful estimations, predictions were made of the lead levels to be expected in animals products and the time needed for depletion of these levels. The appropriate animals were marked to ensure their identification, and the decline in time of the lead levels in milk and offals was conscientiously monitored. In the second week of 1990 the lead concentrations were decreased to levels well below the regulatory limits, and hence the marks were removed from the animals. PMID- 2219087 TI - [Triclabendazole (Fasinex) residue in milk: determination and excretion kinetics]. AB - The determination of triclabendazole (Fasinex) in milk is described. The excretion of triclabendazole and its two main metabolites was measured under field conditions in twenty-five cows. Triclabendazole was administered to cows in a dosage of approximately 12 mg kg-1. The maximum concentration of the main metabolites of triclabendazole (triclabendzole sulphone) measured in milk was 1.415 mg/l. Metabolites could be detected in milk during a ten-day-period. Only 1.5% (maximum) of the triclabendazole administered was eliminated as triclabendazole sulphone by way of milk. PMID- 2219089 TI - [Epidemiology, chemotherapy, anthelmintics-resistance and prevention of Strongylidae infections in horses]. AB - The epidemiology, chemotherapy and control of strongylus infections in the horse are discussed. The annual cycle of various species are stated. In addition the anthelmintics available for treatment and control and the occurrence of anthelmintic resistance are referred to. Finally the options for control under various management conditions (little if any grazing; extensive grazing; intensive grazing) are discussed. PMID- 2219090 TI - [Flatulence in connection with feed]. PMID- 2219091 TI - [Sports during pregnancy]. AB - The aim of this article is to investigate to what extent physical exercise and pregnancy affect each other. Despite an increase in metabolism at rest, the amount of oxygen available for exercise is virtually unaffected by pregnancy. The capability to perform exercise (in W) is equally unaffected, but body weight increases. As a result the maximal running speed and/or distance decreases during pregnancy. The fetus needs a constant supply of oxygen and nutrients. During exercise uterine blood flow decreases. This decrease is linearly correlated with the intensity and the duration of exercise and the maximal reduction averages approximately 25%. Nonetheless, uterine oxygen consumption is maintained. This is the result of compensation through hemoconcentration, redistribution of blood flow within the uterus, and increased oxygen extraction. A harmful effect of physical exercise on the child in utero, such as abortion, hypoxia, or growth retardation, has not been demonstrated so far. Although exercise does not seem to be harmful during normal gestation, one should be careful in case of pregnancy complications such as pregnancy-induced hypertension or premature contractions. PMID- 2219092 TI - [Healthy children and sports]. AB - Sport can be considered as an excellent alternative for unhealthy consumption habits and can compensate far the outcome of a sedentary lifestyle. The youngster can improve technique, coordination and flexibility in an easy way by training programs. Specific weight training programs are not recommended for those under the age of fifteen years. Regular exercise programs at young ages have positive effects on the general education, and during life habitual exercise training reduce the severity of cardiovascular and other diseases. It promotes the fitness of the body and the mind. Sport, a lifetime, must be part of a healthy lifestyle and must be encouraged younger ages. Health effects in a long term depend on exercise programs lasting years. PMID- 2219093 TI - [Athletic injuries in children]. AB - Sports participation can have both beneficial and negative effects. Specific effects are injuries. The change of incidence is dependent on a number of personal and environmental factors. Epidemiological research in the Netherlands in school aged children has shown that sports injuries occur primarily in club sport, even more during competition. The injuries are localised in the lower limbs: especially the knee and the ankle. The injuries are distortions and contusions and fewer fractures and muscle tears. The number of overuse injuries seems to be rising because children are doing increasingly more intensive sport at younger ages. A preventive sports medical examination has been discussed as well as the preventive effect of warming-up and cooling down, stretching exercises, rehabilitation, taping, rules of play and sports facilities. Finally, attention has been given to the general care of sports injuries in the way of active and functional guidance in the healing process. PMID- 2219094 TI - [When sports no longer is a game ... the clinical aspects of competitive sports in children]. AB - Physical and psychic vulnerability in children performing competitive sports may turn an accidental injury into a starting-point for chronic pain. This pain may give rise to serious physical and social restraints. The case histories of two fourteen years old girls are presented. Both patients suffered from overburdening. This phenomenon had not been recognized, or was not explicitly stated at least. Probably, too high expectations from medical help by parents and child played a crucial role. Expectations were twofold: the chronic pain should fit a specific defect caused by the injury, or it should be due to a (serious) disease. Both types of expectations led to disappointments, repeated diagnostic procedures and ineffective therapies. A comprehensive assessment without delay by a multidisciplinary pediatric team is recommended. PMID- 2219095 TI - [sports by children with a bleeding tendency]. AB - In children with bleeding tendency it is a dilemma to go in for sports. The risks and benefits are to be weighed against each other. Mostly there is no need to impede the child's activities. Several sports that safely can be played by children with hemorrhagic diathesis are summed up. Specific aspects of sports by children with thrombocytopenia, Von Willebrand's disease, hemophilia and thrombasthenia are discussed. PMID- 2219096 TI - [Points of departure in sports counseling of children with congenital heart defects]. AB - When counseling children with congenital heart disease who want to participate in sports, it is, generally speaking, preferable to choose a dynamic sport rather than a static one. Also, the degree of intensity is of major importance. In this connection it is useful to differentiate between recreation-oriented and achievement-oriented participation in sports. The extra risks for a child with congenital heart disease are progression of the severely of the anomaly, rhythm disturbances, sudden death, and complications due to medication. For the majority of these children the recommendation will be a strictly individual one, based on the (exercise)electrocardiogram, the 24-hours-ECG monitoring, and the echo Doppler-cardiogram. Invasive techniques are usually unnecessary. PMID- 2219097 TI - [Diabetes mellitus in children and sports]. AB - The short-term and longterm effects of physical exercise and sports on the regulation of diabetes mellitus in children are described. The precise tuning of insulin dosage, food and sports can be achieved with self-control and self regulation. Advisable sports activities and limitations like poor metabolic control are being discussed. Regular physical exercise for diabetic children is advised to prevent lack of movement, also for their health in older age. PMID- 2219098 TI - [Sports in children with COPD]. AB - Doctors and the surroundings of children are often unacquainted with chronic illnesses in combination with physical activity. This leads to prudence. The latter causes restricted physical activity in a lot of children with obstructive lung diseases as a result of an advice not to participate in sports. Consequently, the child may get into psychosocial isolation. Pathogenesis, diagnosis and treatment of exercise-induced bronchoconstriction (EIB) are described. EIB is hardly ever a problem at participating in sports, if treated well. In general, it can be concluded that only a small group of children with diffusion disorder is at risk during some sports. Detection and sport advises for this group will be discussed. PMID- 2219100 TI - [Clinical case. Bull terrier, female, 5 years old]. PMID- 2219099 TI - [Has the animal owner a right to radiographs taken of his animal?]. AB - In the Federal Republic of Germany a veterinarian owns radiographs taken of animals in his practice. They have to be filed like any other results of diagnostic procedures. This is important, because evidence is required in the case of a law suit. On the other hand, it has to be stressed that taking radiographs is the subject of a free contract between owner and veterinarian. So it is possible to take the radiographs solely with the purpose of giving them to the owner, who may have them analysed by any other veterinarian of his choice. This is especially true in hip radiographs, which are evaluated and filed by an adjudicator of the breed association. In any case the radiologist has the obligation to lend the radiographs to another veterinarian on request for inspection. The second veterinarian has to give them back as soon as possible. PMID- 2219101 TI - [Diuretics]. AB - The pharmacology of the commonly used diuretic agents is reviewed, with special reference to the "high ceiling" diuretics and the benzothiadiazines, which are widely used in veterinary medicine. The different clinical indications in veterinary medicine are discussed. PMID- 2219102 TI - [Disseminated candidiasis in a calf. Case report]. AB - The pathological-anatomical and histological examinations of different organs from a calf that died at the age of 9 weeks indicated a disseminated candidiasis. Candida albicans was isolated from brain, lung, liver, spleen, kidney, intestinal lymph nodes and small intestinal contents. The antibiotics administered to the calf by the owner probably initiated the disseminated candidiasis. PMID- 2219104 TI - [Refusal of breeding bulls to eat hay contaminated with horsetail (Equisetum palustre)]. AB - Bulls refused hay from a new batch (coming from a nonintensively fertilized area in Southern Germany). The intake of other components of the ration (silage, concentrates) was not influenced. The visual inspection of the hay revealed a massive contamination (about 12% by mass) by horsetail. According to the reported observations it seems that cattle recognize the plant by its odour, and refuse it if alternative roughage is available, thereby escaping an intoxication. PMID- 2219103 TI - [Recent information about the orf virus of small ruminants]. AB - New scientific findings in the field of immunobiology and diagnosis of parapoxvirus ovis (Orf-virus) as the causal agent of a zoonosis are presented. The adaptation of Orf-virus to cell lines and its in vitro multiplication without difficulties offer the possibility for extensive studies into the biology of parapoxviruses. The development of monoclonal antibodies (MAB) against an attenuated Orf-virus strain (D-1701) led to the elaboration of a simplified, cheap and highly sensitive "antigen detection ELISA" as a diagnostic tool. Moreover the MAB's can be used to identify parapoxvirus in cells of infected tissues (indirect immuno-peroxidase technique) which is an important precondition for more detailed surveillance of the pathogenesis of parapoxvirus infections. The immunobiological behavior of the Orf-virus in its natural hosts (small ruminants) as well as in non-susceptible species (e.g. laboratory animals) is explained by the course of cellular and humoral immune reactions following infection or vaccination. The problems of combat measures against contagious ecthyma (scabby mouth) of sheep and the human Orf-virus infections are discussed. PMID- 2219105 TI - [Corynebacterium suis infection in swine. 1. Clinical diagnosis with special consideration of urine studies and cystoscopy]. AB - Experimental and spontaneous infections with Corynebacterium suis in sows were investigated. In early stages animals show no clinical disorders or only for a short time. However, there are already marked changes in urinary samples (hematuria, proteinuria, leukocyturia, gross alterations). Using an endoscope mucosal irritations can be seen mainly on the floor of the bladders. In chronic cases alterations in urine are more pronounced. If a pyelonephritis is present in addition to the cystitis, general signs of illness are evident including anorexia, emaciation, anemia, subnormal body temperature and abortions. Bladders demonstrate an erosive and ulcerative, hemorrhagic cystitis on the whole mucosal surface. Uremia appears only in late stages of the disease. PMID- 2219106 TI - [Acidification of the stomach contents of weaned piglets--effect of feed quantity and composition]. AB - The pH in the stomach chyme (5-8 hours past offering the diet) of reared piglets was strongly correlated to the ingested feed quantity, a complete acidification of the stomach contents occurred in restrictively fed piglets (15 g diet/kg BW) only. Feeding ad libitum resulted in comparable low pH values in the fundus and pylorus region only, whereas in the cardiac region high pH values (5-6.5) were observed. Formic acid as feed additive (5 ml/kg diet) did not influence the pH in stomach contents significantly, on the other hand the ingestion of a diet with high CaCO3 content (59 g Ca/kg DM) prevented the acidification of the stomach chyme totally. The variation of pH-values in the different areas within the stomach was caused mainly by the variation of hydrochloric acid concentrations, the influence of lactic acid concentration was negligible. PMID- 2219107 TI - [Epizootiology, clinical aspects and therapy of Pasteurella multocida infection in bird patients after cat bite]. AB - Since early 1986, fatal cases of Pasteurella multocida infection following cat bites have been seen regularly among avian patients at our institute. The problems of the epizootiology of this infection are discussed on the basis of research during the last three and a half years. By evaluation of collected data from clinical examinations, autopsies, bacteriological and biochemical diagnosis of isolated strains from birds and cats the possibility of transmission via cat bite is discussed as well as the status of cats and birds in an epizootic chain. Even birds with trivial wounds caused by cats must be classified as emergency patients. The risk of an infection after a cat bite is about 56%. For treatment of a Pasteurella multocida infection Doxycycline should be used. PMID- 2219108 TI - [Radiographic diagnosis of abdominal diseases in foals and ponys. II. Pathologic findings in 60 cases]. AB - A diagnostic approach based on clinical and radiographic examinations for evaluation of young foals and small ponies with acute abdominal discomfort is presented. Standing right to left lateral abdominal radiographs were taken of 54 foals and 6 ponies using a previously described technique. Interpretation of the radiographs was in conjunction with all clinical and laboratory findings and patient management. Using this approach, the site and cause of acute abdominal discomfort could be diagnosed accurately in 55 of 60 (91%) patients as confirmed by clinical, surgical or necropsy findings. Typical radiographs and photographs taken at surgery or at necropsy are presented. Typical radiographic findings, their interpretation and possible underlying gastrointestinal diseases are listed. The incorporation of standing lateral abdominal radiography in the clinical evaluation of foals and ponies with acute abdominal diseases gives findings of high diagnostic significance and should contribute to clinical decision-making. Abdominal radiography can replace data from rectal palpation in foals and ponies. PMID- 2219109 TI - [The applicability of a detection method independent of a laboratory for progesterone in the blood plasma of mares (Hygia progesterone test)]. AB - A rapid progesterone assay for cow's milk was checked as to whether it was applicable to mares' blood plasma. The "Hygia Progesterone-Test" is an on-farm test which serves for qualitative analysis. It is generally unusable for mares' plasma but sufficiently precise only in cases of larger or smaller progesterone levels. In cases of moderate amounts of progesterone the test is imprecise. The test can be carried out quickly and easily, but the preparation of blood samples takes more time than preparation of milk samples. The test can be recommended for usage in veterinary practice only, but not for animal owners. PMID- 2219110 TI - [The frequency of coccidial infection in dog families of different husbandry and breeds in south Germany]. AB - Oocysts and/or sporocysts were detected in 50 litters and 37 bitches of 100 coproscopically examined dog families in Southern Germany. Oocysts of Isospora spp. were excreted by 41 of the 50 positive litters, 36 and 16 litters shedding oocysts of Isospora ohioensis/burrowsi and I. canis, respectively. Sporocysts of Sarcocystis spp. and oocysts of Hammondia heydorni were detected in 12 and 7 litters, respectively. The excretion rates of the dams were arranged analogous to the detection of oocysts of Isospora spp. in 25 animals. Sporocysts of Sarcocystis and oocysts of H. heydorni were excreted by 19 and 6 dams, respectively. With regard to husbandry conditions distinct differences were established only for Isospora spp., because dog families kept in kennels always revealed higher excretion levels than dog mothers and their litters kept indoors. Excretion intensities increased directly proportional to the number of additional adult dogs and the number of litters born per year/stock, reaching maximum values of 80-100%. Analysis revealed no breed-related differences. PMID- 2219111 TI - [Perinatal mortality in dogs. Clinical, bacteriological and pathological studies]. AB - 1. In intensively operated dog breeding kennels bacterial infections are very significant in perinatal mortality. 2. Staph. aureus, Streptococci (type G) and also beta-haemolytic E. coli were transmitted intra-uterine or by the infected genital tract to the puppies. In many cases they are the cause of septicaemic death of the puppies. 3. A second important cause of infection is subclinical mastitis of the bitch, leading to septicaemic death of newborn puppies. 4. Prophylactic hygienic measures make possible a prognosis concerning the risk of perinatal death. This includes examinations of the dog and the bitch ante coitum, bacteriological examination of the genital tract of the bitch, and a bacteriological examination of the milk before the date of birth. 5. Prophylactic hygienic measures in combination with antibiotic treatment of the bitch or the puppies could reduce the losses of puppies to less than 10%. PMID- 2219112 TI - [Isopods as fish parasites]. AB - In January '87 a parasitic isopod not previously described was discovered in the mouth of the fish species Cichla ocellatus from the South American river Demini, a tributary of the Rio Araca. The parasite was classified as Telotha sp. A short description is given. PMID- 2219113 TI - [The diagnostic significance of the protein-creatinine ratio in urine for the differentiation of feline nephropathies]. AB - The normal U-P/C-range in cats was established with urine samples of 19 cats. The upper limiting value was fixed at 0.33 (mean +/- 2s). U-P/C is a reliable parameter for diagnosing proteinuria in the uremic cat. However, only very high U P/C-values allow a conclusion on the type of nephropathy, whereas with moderately increased U-P/C values, do not allow any distinction between feline nephropathies. PMID- 2219114 TI - Renal epithelial amino acid concentrations in mercury-induced and postischemic acute renal failure. AB - The concentration of 18 alpha-amino acids (AAs) in plasma and renal cortical cell water were measured 3 or 24 hr after 1 hr of unilateral renal artery clamping or 24 or 48 hr after 15 mg/kg body weight HgCl2 injection sc as a test of epithelial integrity. Cellular glycine (Gly), hydroxyproline (Hpr), ornithine (Orn), phenylalanine (Phe), serine (Ser), and tryptophan (Trp) concentrations were depressed 24 hr after HgCl2 (p less than 0.05), but the remaining 12 AAs were not distinguishable from control despite the presence of severe renal failure. ARginine (Arg), glutamic acid (Glu), and valine (Val) also were decreased (P less than 0.05) 24 hr later, but concentrations of half of all measured AAs were still normal. Cellular alanine (Ala), Arg, Glu, Gly, Phe, and Ser concentrations were decreased 3 hr after ischemia, p less than 0.05, but 12 AAs were unchanged and only Arg, Phe, Ser, and threonine (Thr) were reduced 24 hr after ischemia was reversed. Concentrations of even the most affected AAs remained notably higher than in plasma in both forms of acute renal failure (ARF). Total loss of AAs from a small proportion of tubular cells would be hidden by essentially normal concentrations in the rest, and such losses may well have occurred. Unless cellular AAs in ARF are almost completely bound, however, the well-maintained cell:plasma AA concentration ratios indicate that cellular energetics were adequate for AA uptake and that epithelial permeability to AAs in the vast majority of cells was not greatly disturbed. Such findings suggest that most of the epithelium, although seriously damaged, had remained viable. PMID- 2219115 TI - Acetaminophen structure-toxicity studies: in vivo covalent binding of a nonhepatotoxic analog, 3-hydroxyacetanilide. AB - High doses of 3-hydroxyacetanilide (3HAA), a structural isomer of acetaminophen, do not produce hepatocellular necrosis in normal male hamsters or in those sensitized to acetaminophen-induced liver damage by pretreatment with a combination of 3-methylcholanthrene, borneol, and diethyl maleate. Although 3HAA was not hepatotoxic, the administration of acetyl-labeled [3H or 14C]3HAA (400 mg/kg, ip) produced levels of covalently bound radiolabel that were similar to those observed after an equimolar, hepatotoxic dose of [G-3H]acetaminophen. The covalent nature of 3HAA binding was demonstrated by retention of the binding after repetitive organic solvent extraction following protease digestion. Hepatic and renal covalent binding after 3HAA was approximately linear with both dose and time. In addition, 3HAA produced only a modest depletion of hepatic glutathione, suggesting the lack of a glutathione threshold. 3-Methylcholanthrene pretreatment increased and pretreatment with cobalt chloride and piperonyl butoxide decreased the hepatic covalent binding of 3HAA, indicating the involvement of cytochrome P450 in the formation of the 3HAA reactive metabolite. The administration of multiple doses or a single dose of [ring-3H]3HAA to hamsters pretreated with a combination of 3-methylcholanthrene, borneol, and diethyl maleate produced hepatic levels of 3HAA covalent binding that were in excess of those observed after a single, hepatotoxic acetaminophen dose. These data suggest that the nature and/or the intracellular processing of the reactive metabolites of acetaminophen and 3HAA are different. These data also demonstrate that absolute levels of covalently bound xenobiotic metabolites cannot be utilized as absolute predictors of cytotoxic potential. PMID- 2219116 TI - Elevation of individual serum bile acids on exposure to trichloroethylene or alpha-naphthylisothiocyanate. AB - Rats were treated with trichloroethylene via intraperitoneal (ip) injection or inhalation, or with ip alpha-naphthylisothiocyanate (ANIT). Serum samples were assayed for indices of liver injury including alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH), alkaline phosphatase (AP), and bilirubin. Liver from some rats was examined for histological appearance. These data were compared to levels of individual serum bile acids (SBA) determined by high-performance liquid chromatography. Trichloroethylene and ANIT, each at their highest dose only, caused elevations in ALT, but not SDH or AP. The highest dose of ANIT also caused elevated serum bilirubin and cholangitis in the liver. SBA were also elevated in response to both trichloroethylene and ANIT, but at doses below those at which other parameters of liver function were increased. For both chemicals, taurocholic acid was the most sensitive of the bile acids assayed, being elevated at the lowest doses tested of 10 mumols/kg for trichloroethylene and 5 mumols/kg for ANIT. As the doses were raised more of the individual bile acids showed increases. On exposure to trichloroethylene via inhalation taurocholic acid was one of two SBA to show elevation. Thus, both trichloroethylene and ANIT cause elevation in SBA at doses well below those which cause an increase in standard indicators of liver dysfunction. This suggests that SBA and perhaps taurocholic acid, in particular, may provide a sensitive tool for studying hepatobiliary effects of chemicals. PMID- 2219117 TI - Mesangial macromolecular uptake in captopril-treated uninephrectomized rats. AB - Captopril, an angiotensin II-converting enzyme inhibitor, ameliorates the renal mesangial lesions associated with subtotal nephrectomy, a process associated with increased mesangial macromolecular flux and injury. In the present study uninephrectomized rats with proteinuria and focal glomerular sclerosis had increased mesangial heat-aggregated human IgG (AHIgG) uptake. However, uninephrectomized rats treated daily with captopril, which failed to develop either glomerular lesions or proteinuria, also had significantly elevated mesangial AHIgG levels. Our results suggest that increased mesangial macromolecular flux may occur independent of altered glomerular permselectivity changes and proteinuria and appears to be related to glomerular hyperfiltration rather than glomerular hypertension. Further, glomerular mesangial sclerosis may not be the direct result of increased mesangial macromolecular flux. PMID- 2219118 TI - Structure-dependent induction of aryl hydrocarbon hydroxylase activity in C57BL/6 mice by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related congeners: mechanistic studies. AB - The time- and dose-dependent induction of murine hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities by five polychlorinated dibenzo-p-dioxin and dibenzofuran congeners showed that the order of induction potency was 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) greater than 2,3,7,8-tetrachlorodibenzofuran (TCDF) greater than 1,2,3,7,8 pentachlorodibenzo-p-dioxin (PCDD) greater than 1,2,3,7,8-pentachlorodibenzofuran (PCDF) greater than 2,3,7-trichlorodibenzo-p-dioxin (TrCDD). These structure induction relationships were comparable to the structure-toxicity and competitive structure-receptor binding relationships previously reported for these compounds. However, using the corresponding radiolabeled congeners, the direct binding Kd values for dissociation of the cytosolic receptor-ligand complexes were 9.52, 7.96, 1.27, 3.10, and 8.31 nM for the 2,3,7,8-TCDD, 2,3,7,8-TCDF, 2,3,7-TrCDD, 1,2,3,7,8-PCDD, and 1,2,3,7,8-PCDF congeners and these data were clearly not structure dependent (i.e., similar to the structure-activity relationships). Some of the molecular properties for several radioligand-receptor complexes were similar; for example, the sedimentation coefficients for the cytosolic and nuclear receptor complexes varied from 8.8-10.4 S and 5.98-7.0 S, respectively, and the nuclear receptor complexes for all the radioligands eluted from a DNA Sepharose column at salt concentrations of 0.27-0.29 M. Treatment of the mice with a maximum inducing dose of 2,3,7,8-[3H]TCDD resulted in a time-dependent formation of the nuclear receptor complex which was maximized between 16-24 hr and subsequently decreased up to 72 hr after initial exposure. In parallel studies, the nuclear receptor complex levels were determined 16 hr after treatment of the mice with different doses (2.25, 4.5, and 45 micrograms/kg) of all five radioligands. The results showed that at submaximal induction of the monooxygenase enzyme activities there was a linear correlation between the induced AHH or EROD activities (after 32 hr) and the corresponding nuclear receptor complex levels. It was also apparent from the data that the relative levels of nuclear receptor complex were structure dependent and this suggests that the transformation or activation of cytosolic receptor complexes may be a ligand structure-dependent process which correlates with the observed structure activity relationships for 2,3,7,8-TCDD and related compounds. PMID- 2219119 TI - Bioactivation of 3-methylindole by isolated rabbit lung cells. AB - 3-Methylindole (3MI) is a pneumotoxin that causes selective lung lesions indicative of Clara cell and alveolar epithelial cell damage in ruminants and rodents. The present study examined the cytotoxicity of 3MI to isolated rabbit Clara cells, type II alveolar epithelial cells, and alveolar macrophages. 3MI produced a dose-dependent cytotoxicity to Clara cells detectable within 1 hr of incubation at 37 degrees C which reached a maximum at 3 hr. Concentrations of 0.25 and 0.5 mM 3MI were cytotoxic to Clara cells, while type II and alveolar macrophages required 1 mM 3MI before cytotoxicity was observed. The cytochrome P450 suicide substrate inhibitor, 1-aminobenzotriazole, inhibited 3MI-induced cytotoxicity in Clara cells, type II cells, and alveolar macrophages. These observations were consistent with a cytochrome P450-mediated bioactivation of 3MI to a toxic intermediate. Studies with a trideuteromethyl analog of 3MI demonstrated a much reduced cytotoxicity to Clara cells as well as to type II cells, and macrophages. The deuterium isotope effect suggested that C-H bond breakage at the 3-methyl group is a requisite oxidative transformation in the bioactivation of 3MI to a selective lung cell cytotoxin. The selectivity of cellular cytotoxicity is probably associated with higher rates of bioactivation by Clara cell cytochrome P450 monooxygenases compared to those of type II cells and macrophages. These studies demonstrate that 3MI is bioactivated in isolated pulmonary cells without the intervention of other organs and that bioactivation requires functional cytochrome P450 enzymes. PMID- 2219120 TI - High dietary protein regimens provide significant protection from mercury nephrotoxicity in rats. AB - The effects of high protein dietary regimens prior to the administration of inorganic mercury were investigated. Male Sprague-Dawley rats were pair-fed on purified test diets containing either normal (20%) or high (60%) concentrations of protein. Mercury was administered as a single intravenous injection of mercuric chloride (1 mg/kg). All rats maintained on normal dietary protein prior to and following mercury injection exhibited severe kidney dysfunction, extensive necrosis of both second (S2) and third (S3) segments of the kidney proximal tubules, and 100% mortality. In contrast, rats maintained on high dietary protein for 48 hr or longer just prior to mercury injection and returned to normal dietary protein immediately following mercury administration all survived and exhibited normal serum creatinine and BUN values within 4 days following mercury administration. The kidneys of this latter group took up significantly less radiolabeled mercury during the first 12 hr following mercury injection, and exhibited relatively little damage to the second segments (S2) of the proximal tubules. The third segments (S3) of the proximal tubules, however, exhibited the same degree of necrosis as that observed in the control group. Maintaining rats on high dietary protein regimens for shorter periods of time prior to mercury infusion (i.e., 12 or 24 hr) also dramatically reduced subsequent acute renal failure and improved survival, although not to the extent noted following 48 hr or longer on these diets. These observations suggested that high dietary protein regimens may protect from mercury nephrotoxicity by reducing mercury uptake to the second segments (S2) of the proximal tubules during the initial period of exposure to intravenously administered mercury. PMID- 2219121 TI - Formate metabolism in young swine. AB - Formate generated from methanol metabolism in vivo is the chemical entity responsible for the development of the methanol toxicity syndrome in the monkey. Compared to rats, monkeys are in a state of folate deficiency. This leads to a decreased ability to dispose of formate generated leading to its accumulation and the subsequent development of the classic symptoms of methanol toxicity. Rats possess a more efficient folate system; therefore, they metabolize formate very readily and do not exhibit methanol toxicity symptoms. In this report, the hepatic folate content and the ability to handle a formate "load" were evaluated in another animal species, the pig. The results obtained indicate that the pig, compared to all other species studied, has extremely low levels of folates and very low levels of a key enzyme in the folate pathway, namely 10-formyl H4folate dehydrogenase. Also the pig's ability to dispose of formate was extremely limited and slower than that observed in rats or monkeys. These results suggest that the pig may be a suitable animal model for studying formate metabolism and possibly methanol toxicity. PMID- 2219122 TI - Learning and memory deficits in rats following exposure to 3,3' iminodipropionitrile. AB - Rats were examined using a learning and memory test battery 4 weeks following exposure to 3,3'-iminodipropionitrile (IDPN). Initial testing revealed deficits in olfactory discrimination and passive avoidance (PA) conditioning. In order to dissociate learning and performance effects, additional tests were conducted. First, to rule out the possibility that IDPN reduced the aversiveness of foot shock, rats were tested in a simple shock sensitivity paradigm. The results indicated no change in shock sensitivity produced by IDPN. Second, to determine if the hyperactivity produced by IDPN was responsible for deficits in conditioning, several additional tests were conducted including (a) repeated trials active avoidance (AA) and PA conditioning, (b) a PA study which included both a 1- and 24-hr training-testing interval, and (c) long-delay flavor-aversion conditioning. Rats treated with IDPN required more conditioning trials to reach criterion on both AA and PA procedures suggesting that they were capable of performing the required response but acquired those responses at a much slower rate. The deficits in PA conditioning were similar at both the 1- and 24-hr training-testing interval. Finally, the effects of IDPN on flavor-aversion conditioning depended on the delay separating flavor intake and lithium administration during conditioning. Rats treated with IDPN demonstrated robust flavor aversions when trained with a 30-min but not with a 6-hr delay. In summary, the neurotoxic profile of effects produced by IDPN must be expanded to include a prominent cognitive component characterized by protracted deficits in learning and memory capacity. The present experiment illustrates how chemically induced disruption of learning and memory produced by IDPN can be experimentally dissociated from associate neurological symptoms using a simple, routine battery of neurobehavioral tests. PMID- 2219124 TI - Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen. AB - The effects of oxygen at 1, 2, and 3, atmospheres absolute (ATA) were assessed on brain lipid peroxidation caused by carbon monoxide (CO) poisoning in a rat model. Oxygen at 3 ATA, but not 1 ATA, was found to prevent brain lipid peroxidation when administered to rats for 45 min, beginning 45 min subsequent to CO poisoning. Oxygen at 2 ATA had an intermediate effect. The action of hyperbaric oxygen could not be attributed to a more rapid diminution of carboxyhemoglobin, and appears to occur at the level of the brain tissue. PMID- 2219123 TI - Inhibition of rat liver monooxygenase activities by 2-methyl-1,4-naphthoquinone (menadione). AB - In rat liver microsomes, 2-methyl-1,4-naphthoquinone (menadione) inhibits cytochrome P450 (cyt P450)-mediated aniline-p-hydroxylation and aminopyrine-N demethylation with Ki values of 12 and 14.5 microM, respectively. The inhibitions of aniline-p-hydroxylation and aminopyrine-N-demethylation are mixed uncompetitive-noncompetitive and mixed competitive-noncompetitive, respectively. NADP antagonizes the inhibitory effect of menadione on aniline-p-hydroxylase activity but not that on aminopyrine-N-demethylase activity. Menadione does not give rise to any spectral change of cyt P450, but modifies the type I binding spectrum induced by aminopyrine. In contrast, menadione does not change the type II binding spectrum induced by aniline. These results indicate that menadione may inhibit aniline-p-hydroxylase activity by acting as a substrate for NADPH-cyt P450 reductase in the place of cyt P450 and inhibit aminopyrine-N-demethylase activity by impairing the binding of aminopyrine to cyt P450. PMID- 2219125 TI - Induction of DNA synthesis by sodium phenobarbital, uracil, and sodium saccharin in urinary bladder of the F344 rat. AB - DNA synthesis in urothelial cells was determined 2, 4, 6, 10, and 16 weeks following dietary administration of promoters of bladder tumors to weanling male F344 rats. The experimental groups were fed AIN-76A diet or this diet containing 0.15% sodium phenobarbital, 3% uracil, 5% sodium saccharin, 2% sodium bicarbonate, or a combination of 5% sodium saccharin and 2% sodium bicarbonate. Two other groups were given Wayne rodent chow alone or in combination with 5% sodium saccharin. A group of rats given a drinking water containing 0.01% N-butyl N-(4-hydroxybutyl)nitrosamine served as a positive control. With the exception of phenobarbital which increased the labeling index but did not induce hyperplasia, all other compounds increased the labeling index and induced hyperplasia. The combination of sodium saccharin and sodium bicarbonate was more effective than either compound alone in increasing the labeling index. Sodium saccharin was equally active when incorporated in either the AIN diet or the Wayne rodent chow. The present results suggest that a fundamental mechanism of bladder tumor promotion may be due to an increased DNA synthesis which leads to an increased turnover rate of urothelial cells rather than hyperplasia. However, since sodium saccharin is a promoter when incorporated into the Wayne diet but not into the AIN diet, the ability to stimulate DNA synthesis may be an important but insufficient condition for promotion by saccharin. PMID- 2219127 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin enhances responsiveness to post-ingestive satiety signals. AB - The present study was designed to characterize the hypophagia that is a salient feature of the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced wasting syndrome. When TCDD-treated Long-Evans (L-E; dose 50 micrograms/kg) and Han Wistar (H-W; 3000 micrograms/kg) rats were offered a simultaneous choice of three diets differing in their macronutrient composition, no selective aversion was seen to any of the varieties, although total energy intake decreased drastically and especially so in L-E rats. Further studies in H-W rats showed that TCDD treatment leads to a permanent retardation of weight gain accompanied by a decreased intake of chow and of a 10% sucrose solution, and to a reduced or unchanged consumption of water. In contrast, there was a progressive increase in saccharin drinking (when offered as the only choice) in TCDD-dosed rats with time. TCDD-treated animals also tended to consume a greater proportion of their daily feed intake during the daytime. These results imply that TCDD induces aversion to eating energy-providing food, irrespective of its type, and that TCDD exerts this at least in part by sensitizing the rats to post-ingestive satiety factors. PMID- 2219126 TI - Induction of metallothionein synthesis by zinc in cadmium pretreated rats. AB - The ability of zinc (Zn) salts to induce the synthesis of metallothionein (MT) in liver, kidney and pancreas of rats pretreated with cadmium (Cd) salts was investigated. Twenty-four hours after either CdCl2 (2.0 mg Cd/kg, s.c.) or saline pretreatment, rats were injected with saline, CdCl2 (2.0 mg Cd/kg, s.c.) or ZnSO4 (20 mg Zn/kg, s.c.) and the concentrations of MT and MT-1 mRNA in tissues subsequently measured. After a single injection of Cd salts, concentrations of MT and MT-1 mRNA were significantly increased in liver as compared to control. With two injections of Cd, the accumulation of MT in liver was approximately twice the levels of MT following a single injection of Cd. In kidney, MT and MT-1 mRNA expression were significantly increased only after two injections of Cd and in the pancreas, Cd injections did not alter either MT content or MT-1 mRNA expression. Treatment with Zn salts increased MT concentrations in both liver and pancreas. However, the pancreas was the most responsive to injections of Zn salts as compared to the liver in terms of increases in both protein concentration and MT-1 mRNA expression. When Zn injection was preceded by a Cd injection, induction as measured by MT-1 mRNA and MT concentrations were approximately additive in liver. In kidney, although Cd or Zn treatment separately had no effect on MT or MT-1 mRNA content, injection of Cd followed by Zn resulted in significantly increased levels of renal MT and MT-1 mRNA. Fractionation of liver cytosols on a Sephadex G-75 column revealed that in animals receiving two injections of Cd, virtually all the Cd was associated with MT whereas Zn was distributed between both high molecular weight (HMW) proteins and MT. In animals receiving both Cd and Zn injections, cytosolic Cd was still bound predominantly to the MT fraction, while the proportion of cytosolic Zn associated with MT increased. The results of this study suggest that, treatment with Cd salts followed by Zn salt injection can induce further synthesis of MT in liver, kidney and pancreas with subsequent binding of both Zn and Cd to the intracellular MT. PMID- 2219128 TI - Ingestion of chlorinated water has no effect upon indicators of cardiovascular disease in pigeons. AB - Cardiovascular disease (CVD) accounts for nearly half the deaths, yearly, in the United States. The arterio(athero)sclerotic plaque is the principal lesion of CVD. The White Carneau (WC) pigeon is an animal model that has been employed extensively for studying CVD. Cholesterol (CHOL) feeding aggravates atherosclerosis in WC pigeons greater than 2 years old. In 1986, two reports appeared from a single laboratory claiming a direct effect of drinking chlorinated (Cl) water upon lipid levels and plaque development in young (less than 1 year) WC pigeons. These are the only reports of such direct effects, to date. Three months' exposure to 2 ppm or 15 ppm Cl in the drinking water, resulted in increased circulating CHOL levels in young male WC pigeons fed a normocholesterolemic (NC) diet in which Ca2+ levels were reduced. In addition, at both Cl concentrations there was a significant increase in plaque size, compared to controls. Pigeons in the 2 ppm group also exhibited elevated low density lipoprotein (LDL) levels after 3 months on the NC diet. These findings, if extrapolated to man, could have considerable public health consequences, since nearly 200 million people in the United States drink Cl water. We have carried out a similar set of studies but with strikingly different results. We used the same suppliers of pigeons and feed as did the authors of the 1986 reports and followed their approach where possible. Six month-old male WC pigeons drank water with 2 ppm or 15 ppm Cl (pH 8.5) and ate a NC diet with Ca2+ reduced to 80% of normal. At both 1 and 3 months, body weight, CHOL, triglyceride and LDL levels were unaffected by drinking Cl water. There was also no effect of Cl water on plaque size after 3 months. Thus, we found no evidence that drinking chlorinated water has any effect upon circulating lipid levels or upon the development of arteriosclerotic plaques, in this animal model. PMID- 2219129 TI - Interactions between paraquat, endogenous lung amines' antioxidants and isolated mouse Clara cells. AB - The ability of paraquat to damage mouse lung Clara cells in the presence and absence of herbicide inhibitors is investigated using a cell culture system. Clara cell damage is assessed on the loss of nitroblue tetrazolium reductase activity and the inability to attach and spread on an extracellular matrix. Endogenous amines such as putrescine and spermidine reduce paraquat-induced damage at low concentrations indicating that they compete for the same cell surface receptor as paraquat and thus potentially block the accumulation of the herbicide. The efficacy of 10 microM exogenous putrescine as a protectant is reduced the longer the time before it is added to the cultures. Clara cells contain high levels of NADPH-dependent P-450 reductase which is required to redox cycle the paraquat and generate reactive oxygen radicals. Compounds with antioxidant properties are examined for their ability to reduce the Clara cell damage. Cystamine, the disulphide form of the naturally occurring thiol, cysteamine, and taurine, a metabolite of cystamine, both of which are accumulated in the lung, do not reduce paraquat-induced Clara cell damage. Another antioxidant, alpha-tocopherol is also ineffective but reduced glutathione (GSH), present in high quantities (3.2 mM) in clara cells, could reduce damage to the cultured cells. Cysteine, a precursor of GSH, can also prevent Clara cell damage when the concentration of paraquat is low. PMID- 2219130 TI - Liver tumor induction in B6C3F1 mice by dichloroacetate and trichloroacetate. AB - Male and female B6C3F1 mice were administered dichloroacetate (DCA) and trichloroacetate (TCA) in their drinking water at concentrations of 1 or 2 g/l for up to 52 weeks. Both compounds induced hepatoproliferative lesions (HPL) in male mice, including hepatocellular nodules, adenomas and hepatocellular carcinomas within 12 months. The induction of HPL by TCA was linear with dose. In contrast, the response to DCA increased sharply with the increase in concentration from 1 to 2 g/l. Suspension of DCA treatment at 37 weeks resulted in the same number of HPL at 52 weeks that would have been predicted on the basis of the total dose administered. However, none of the lesions in this treatment group progressed to hepatocellular carcinomas. Conversely, the yield of HPL at 52 weeks when TCA treatment was suspended at 37 weeks was significantly below that which would have been predicted by the total dose administered. In this case, 3 of 5 remaining lesions were hepatocellular carcinomas. Throughout active treatment DCA-treated mice displayed greatly enlarged livers characterized by a marked cytomegaly and massive accumulations of glycogen in hepatocytes throughout the liver. Areas of focal necrosis were seen throughout the liver. TCA produced small increases in cell size and much a more modest accumulation of glycogen. Focal necrotic damage did not occur in TCA-treated animals. TCA produced marked accumulations of lipofuscin in the liver. Lipofuscin accumulation was less marked with DCA. These data confirm earlier observations that DCA and TCA are capable of inducing hepatic tumors in B6C3F1 mice and argue that the mechanisms involved in tumor induction differ substantially between these two similar compounds. Tumorigenesis by DCA may depend largely on stimulation of cell division secondary to hepatotoxic damage. On the other hand, TCA appears to increase lipid peroxidation, suggesting that production of radicals may be responsible for its effects. PMID- 2219131 TI - Early induction of reparative hyperplasia in the liver of B6C3F1 mice treated with dichloroacetate and trichloroacetate. AB - Trichloroacetate (TCA) and dichloroacetate (DCA) were administered at concentrations of 0, 300, 1000 or 2000 mg/l in the drinking water of male B6C3F1 and male and female Swiss-Webster mice for up to 14 days. At 2, 5 or 14 days of treatment, mice were injected with [3H]thymidine 2 h prior to sacrifice. The livers were examined histologically and autoradiographically and DNA was isolated and counted. As observed in chronic studies dichloroacetate induced a marked increase in liver weights, but only after 14 days of treatment and local necrosis in both B6C3F1 and Swiss-Webster mice. A significant increase in the labeling index of hepatocytes was observed in animals treated with DCA, but only at 14 days of treatment. No such increases were observed in animals treated with TCA. In contrast, significant increases in [3H]thymidine were observed in the livers of both DCA- and TCA-treated animals after 5 days of treatment. This effect remained apparent with TCA after 14 days of treatment. These data support the hypothesis that the tumorigenic effect of DCA is strongly influenced by necrosis and reparative hyperplasia. On the other hand, the carcinogenic effects of TCA appear to be more closely associated with [3H]thymidine incorporation that can be separated from cell division, suggesting an elevated rate of repair synthesis of DNA. Thus the carcinogenic effects of TCA (and perhaps lower doses of DCA) may involve damage to DNA. PMID- 2219132 TI - Increased expression of c-myc and c-Ha-ras in dichloroacetate and trichloroacetate-induced liver tumors in B6C3F1 mice. AB - The expression of c-myc and c-H-ras in hyperplastic nodules and hepatocellular carcinomas induced in male B6C3F1 mice after chronic administration of dichloroacetate (DCA) and trichloroacetate (TCA) was studied using in situ hybridization. Expression of c-myc and c-H-ras mRNA was increased in both nodules and carcinomas relative to surrounding tissue and tissues obtained from control animals. Myc expression was similar in hyperplastic nodules and carcinomas induced by DCA, but was significantly higher in TCA-induced carcinomas than in hyperplastic nodules and carcinomas produced by DCA. In carcinomas from animals whose TCA treatment was suspended at 37 weeks, c-myc expression remained high relative to control and surrounding liver tissue at 52 weeks. In contrast, the expression of c-H-ras was consistently elevated in carcinomas from both treatments relative to hyperplastic nodules and non-tumor tissue. Within carcinomas from both treatments, focal areas could be located which expressed even higher levels of c-myc. This heterogeneity was not observed in carcinomas hybridized to c-H-ras-probes. These data suggest that elevated expression of c-H ras and c-myc might play an important role in the development of hepatic tumors in B6C3F1 mice. Elevated expression of c-H-ras was closely associated with malignancy. Increased c-myc expression does not seem necessary for progression to the malignant state. On the other hand, the increased expression of c-myc appears related to the earlier progression of TCA-induced tumors to the malignant state. PMID- 2219133 TI - Prevalence of metallothioneinuria among the population living in the Kakehashi River basin in Japan--an epidemiological study. AB - An epidemiological study to evaluate cadmium-induced renal dysfunction by urinary metallothionein levels was carried out in an environmentally-exposed Japanese population. The study population consisted of 3168 men and women from a cadmium polluted area who were 50 years and older and 291 individuals from a non-polluted area. The mean metallothionein levels in urine of the control population were 138.2 +/- 2.1 and 198.6 +/- 1.9 microgram/g creatinine for men and women, respectively. The corresponding values for the cadmium-exposed population were 157.8 +/- 2.2 and 248.0 +/- 2.2. The 97.5% upper limits for men in the control population was determined to be 638 and for women 693 microgram MT/g creatinine. Based on these values as the cut-off levels, the prevalence of metallothioneinuria was calculated to be 4.6% in men and 8.4% in women from the cadmium-polluted area. Further selection of the population, based on life-time residence in the polluted area accompanied with the consumption of cadmium containing rice, showed an even greater prevalence of metallothioneinuria: 5.4% in men and 10.9% in women of all ages. The prevalence of metallothioneinuria increased with age and duration of residence in the polluted area. These results suggest that metallothioneinuria can be used as an indicator of renal dysfunction due to environmental cadmium exposure. PMID- 2219134 TI - Subchronic 90 day toxicity of dichloroacetic and trichloroacetic acid in rats. AB - Male Sprague-Dawley rats were treated with either dichloroacetic acid (DCA) or trichloroacetic acid (TCA) in the drinking water at levels of 0, 50, 500 and 5000 ppm for a period of 90 days to determine the toxicities associated with subchronic exposure. All animals were sacrificed and examined for gross and histopathologic lesions, serochemical changes, immune dysfunction, hepatic peroxisomal and mixed function oxidase enzyme induction and organ-body weight changes. Animals treated with DCA had decreased body weight gains (500 and 5000 ppm) and decreased total serum protein (all doses). Rats given either TCA (5000 ppm) or DCA (500 or 5000 ppm) had increased liver and kidney organ to body weight ratios. Rats offered DCA had significantly elevated alkaline phosphatase (500 and 5000 ppm) and alanine-amino transferase (5000 ppm). No consistent immunotoxicity was observed in animals exposed to either compound. Rats treated with 5000 ppm TCA or DCA had significantly increased hepatic peroxisomal beta-oxidation activity. These data, along with histopathologic changes, suggest that TCA and DCA produce substantial systemic organ toxicity to the liver and kidney during a 90-day subchronic exposure, although only at doses greater than those expected to occur in the environment. PMID- 2219135 TI - Cadmium teratogenicity and its relationship with metallothionein gene expression in midgestation mouse embryos. AB - As an approach toward understanding the mechanisms by which cadmium (Cd) exerts its teratogenic effects, the expression and metal regulation of the metallothionein (MT) genes in midgestation mouse embryos were studied by Northern blot and in situ hybridization. Maternal injection of a teratogenic dosage of Cd (50 mumol Cd/kg body wt) did not induce MT mRNA in day 10 (D10) CD-1 mouse embryos, whereas zinc (Zn) (50 mumol/kg was an effective inducer. In contrast, Cd was about 10-fold more potent than Zn at rapidly inducing MT mRNA in D10 embryos incubated in vitro in medium containing micromolar concentrations of these metals. This suggests that following maternal injection, Cd but not Zn is prevented from reaching the D10 embryo and establishes that the embryonic MT genes are not refractory to metal induction, which might have explained the sensitivity of the embryo to Cd. MT mRNA was detected at high levels only in the extraembryonic membranes of D9 embryos exposed to Cd in vivo. On days 9 and 10, no embryonic cell types contained detectable levels of MT mRNA. This mRNA was detected first at low levels in hepatocytes on D11, soon after formation of liver and these levels increased dramatically by D12. Therefore, Cd teratogenicity was not associated with high levels of cell type-specific expression of the MT genes in Cd-sensitive regions of the embryo (neural tube, limb bud), that might have served to target Cd to these cells. Taken together, the results of this study suggest that Cd teratogenicity reflects damage to maternal or extraembryonic tissues. However, the results cannot exclude the possibility that certain cells in the embryo are exceptionally sensitive to low levels of Cd. PMID- 2219136 TI - Effect of acetone administration on renal, pulmonary and hepatic monooxygenase activities in hamster. AB - Administration of acetone in drinking water to Syrian Golden hamsters for 9-10 days altered microsomal P-450 dependent monooxygenase activities in the liver and the kidney but not in the lung. While hepatic microsomal NADPH-cytochrome c reductase was unaffected, cytochrome b5 and P-450 content increased (about 100%) in liver but not in kidney. Furthermore acetone treatment resulted in an increase of microsomal reverse type I binding with DMSO and in an increase in the P 450IIE1-linked renal and hepatic activities such as aniline hydroxylase (AnH) and p-nitrophenol hydroxylase (pNPH). The SDS-PAGE analysis confirmed the induction in acetone-treated microsomes of a hepatic protein with the M.W. of ethanol inducible P-450IIE1 of hamster. The acetone treatment however, unlike ethanol, induced other activities such as benzphetamine N-demethylase and ethoxycoumarin O deethylase in liver and aminopyrine N-demethylase in kidney. No change of ethoxyresorufin O-deethylase and pentoxyresorufin O-depentylase was observed in either renal or hepatic microsomes. Addition of acetone in vitro had an inhibitory effect on pNPH by hepatic microsomes from control or acetone induced hamsters, while AnH was not affected. Interruption of acetone administration for 24 h resulted in a return of AnH and pNPH activities to essentially basal levels in the liver suggesting a rapid turnover of the hamster P-450IIE1 (ham P-450j). Our results indicate that, as found in rat, acetone is a good inducer of the P 450IIE1 (ham P-450j) in hamster in both the liver and kidney. However other P-450 forms, such as, probably, the renal and hepatic P-450IIB1, are also induced. Thus acetone-treated hamsters, which, in certain respects, show a qualitatively different induction pattern from that reported for ethanol, can be used as an useful animal model to study the toxicity of certain xenobiotics. PMID- 2219137 TI - Developmental toxicity of in utero exposure to toluene on malnourished and well nourished rats. AB - The aim of the present study was to investigate the effects of toluene on fetal development in well nourished and malnourished rats. Long-term behavioural consequences after in utero exposure were also studied. Toluene (1.2 g/kg s.c.) was administered daily to well nourished and to malnourished (food restricted to 50% of ad libitum intake) pregnant rats, during the second (8-15 days) or the third week of pregnancy (14-20 days). Offspring were evaluated for malformations, development of the skeleton, prenatal growth of the brain and liver, postnatal growth and long lasting behavioural effects. In utero exposure to toluene during the third week of pregnancy resulted in low body weight at birth, which persisted in the male offspring into adulthood. Malnutrition increased fetal susceptibility to the effects of toluene as indicated by evaluation of the development of the skeleton. Behavioral tests performed when the pups were 30 and 90 days old showed effects of in utero malnutrition (increased ambulation and worse performance in a shuttle box), but no behavioural effects related to toluene exposure were detected. These data indicate that in utero exposure to toluene can have long lasting effects on body growth and that maternal malnutrition increases the risk for toluene fetotoxicity. PMID- 2219138 TI - Immune alterations in rats following subacute exposure to tributyltin oxide. AB - Adult male Fischer 344 rats were dosed by oral gavage with bis(tri-n butyltin)oxide (TBTO) in peanut oil for 10 consecutive days, at dosages ranging from 1.25 to 15 mg/kg/day. Other groups of rats were dosed daily for 10 days by oral gavage with cyclophosphamide (CY) at dosages ranging from 0.75 to 6 mg/kg/day. These rats served as positive controls for the immune assays employed. The immune function parameters examined included the following: delayed-type hypersensitivity (DTH) and antibody responses to bovine serum albumin (BSA), primary antibody responses to sheep red blood cells (SRBC) and trinitrophenyl lipopolysaccharide (TNP-LPS) and enumeration of splenic lymphocyte populations. The DTH and antibody responses to BSA were not affected by TBTO exposure; however these responses were suppressed in rats dosed with CY at 6 mg/kg/day. The plaque forming cell (PFC) response to the T cell-dependent antigen SRBC was enhanced in rats dosed with TBTO at from 5 to 15 mg/kg/day. On the other hand, the PFC response to the T cell-independent antigen TNP-LPS was unaffected by TBTO exposure. Rats dosed with CY had suppressed PFC responses to SRBC and TNP-LPS at dosages of 3 and 6 mg/kg/day, respectively. Enumeration of splenic lymphocyte populations from TBTO-exposed rats revealed a reduction in OX8- but not W3/25- or IgG-positive cells. These results, as well as results from an earlier study from this lab, suggest that T lymphocytes are a primary target for TBTO-induced immune alterations and that the enhancement of the PFC response to SRBC in TBTO-exposed rats may be mediated by alterations in the suppressor (OX8-positive) T lymphocyte population. PMID- 2219139 TI - Excretion and blood radioactivity levels following [14C]senecionine administration in the rat. AB - Macrocyclic pyrrolizidine alkaloids (PAs) are a mixed group of phytotoxins with similar chemical structures and varying biological effects. A commonly studied member of this group is senecionine (SEN) which causes hepatotoxicity. We have undertaken metabolism and excretion studies of SEN in rats to provide data for comparison between PAs and to evaluate the potential role of metabolism and excretion in toxicity. Following intravenous administration of [14C]SEN (60 mg/kg, 10 microCi/kg), bile, urine and blood were collected over a 7-h period. Of the total administered radioactivity, 44% and 43% were excreted in the bile and urine, respectively. Using mass spectroscopy, senecionine N-oxide (SENNOX) was identified as the major metabolite in bile (52% of 44%) and urine (30% of 43%). For the total 7 h, less than 5% in bile and 18% in urine was excreted as parent alkaloid. The plasma concentration of Senecionine-equivalents/g (SEN-EQ/g) decreased from 107 to 12 nmol, while red blood cell (RBC) concentrations declined from 109 to 26 nmol/g. Without bile collection, the plasma levels of SEN-EQ were similar, while the final RBC level was almost double (47 vs. 26 nmol/g) and total radioactivity excreted in the urine was increased (59% vs. 43%). Biliary pyrrolic metabolites were estimated to be 1.43 mg, using a dehydroretronectin standard. PMID- 2219140 TI - Arsenic-cadmium interaction in rats. AB - Simultaneous exposure to cadmium and arsenic is highly probable in the urban area of San Luis Potosi, Mexico due to common localization of copper and zinc smelters. Therefore, in this work, rats were intraperitoneally exposed either to cadmium or arsenic alone, or simultaneously to both metals. The effects of these treatments on three different toxicological parameters were studied. Cadmium modified the LD50 of arsenic and conversely arsenic modified the LD50 for cadmium. At the histopathological level, arsenic appeared to protect against the cadmium effects, especially on testes. This protective effect seemed to be related to the glutathione levels found in this tissue: rats exposed to both arsenic and cadmium, presented glutathione values intermediate to those observed after exposure to either metal alone; arsenic had the highest value and cadmium the lowest. In liver, rats exposed to arsenic, cadmium or arsenic and cadmium, presented glutathione values below those in the saline group, with the lowest value corresponding to the arsenic and cadmium treatment. The results appear to support the proposed interaction between arsenic and cadmium and coexposure to both metals seems to alter certain effects produced by either metal alone. PMID- 2219141 TI - Renal, hepatic, cardiac and thymic acute toxicity afforded by bis(helenalinyl)malonate in BDF1 mice. AB - Bis(helenalinyl)malonate [BHM], a pharmacologically active sesquiterpene lactone potentially useful as an antineoplastic agent, proved to be less toxic than its parent compound, helenalin. Its LD50 in BDF1 mice, i.p. was more than twice that of helenalin. Its lower toxicity allowed a higher therapeutic dose (15 mg/kg/day vs. 8 mg/kg/day for helenalin) which, in turn, afforded a greater T/C% (261 vs. 161). When BHM was employed at its therapeutic dose of 15 mg/kg/day, no marked toxicity was evident after three daily doses. However, continuation of treatment at this level led to both kidney and liver toxicity as measured by clinical chemistry parameters. Histological lesions in the thymus and kidney were demonstrated within 48 h at 25 mg/kg as a single dose. Apparently the toxicity was delayed with BHM but accumulated over time. Transient cardiotoxicity occurred with the drug and the agent was suspected of causing intestinal blockage. PMID- 2219142 TI - Penetration of [3H]T-2 mycotoxin through abraded and intact skin and methods to decontaminate [3H]T-2 mycotoxin from abrasions. AB - Penetration of 50 muCi of [3H]T-2 mycotoxin through abraded and intact skin was studied in anesthetized rats sacrificed at 5, 15, 30, 45, 60 and 90 min post exposure. The greatest penetration was through abraded skin (49 +/- 7%) at 90 min post-exposure, whereas penetration through intact skin (2 +/- 3%) was substantially less (P less than 0.0015). Methods to decontaminate [3H]T-2 mycotoxin from abraded skin over time were studied. Treatment of [3H]T-2 contaminated abrasions by applying Trau + Medic dressing, applying Charcoal Cloth Anti-bacterial Field Dressing (Charcoal Dressing), or swabbing with povidone iodine 30 min post-exposure removed 17-32% of the applied [3H]T-2. Immediate blotting with immediate removal of the dressings absorbed 103 +/- 4% (Trau + Medic) and 87 +/- 4% (Charcoal Dressing) of the applied [3H]T-2, while immediate blotting and leaving the dressing in place for 30 min removed 91 +/- 5% (Trau + Medic) and 76 +/- 3% (Charcoal Dressing). It appears that immediate blotting with either dressing followed by immediate removal before application of a clean dressing is an effective method for decontaminating [3H]T-2 from abrasions. PMID- 2219143 TI - Phospholipase A2 in venom extracts from honey bees (Apis mellifera L.) of different ages. AB - We measured phospholipase A2 activity in the venom of worker honey bees (Apis mellifera L.) of known ages using chemical (titrimetric) and radioallergosorbent methods. The two techniques give similar results. Low levels of phospholipase A2 are present in the venom system at the time of eclosion. Phospholipase A2 activity in the venom increases steadily through the 10 days after eclosion. Maximal phospholipase A2 levels (about 40 micrograms phospholipase A2/venom sac) are maintained through the rest of the life of a worker bee in summer. PMID- 2219144 TI - Pathogenesis of hemorrhage induced by bilitoxin, a hemorrhagic toxin isolated from the venom of the common cantil (Agkistrodon bilineatus bilineatus). AB - The pathogenesis of hemorrhage induced by the i.m. injection of the hemorrhagic toxin, bilitoxin, was studied using light and electron microscopy. White mice were injected with sublethal doses of the toxin, and tissue samples were obtained at 5 and 30 min, and 1, 3 and 24 hr after the injection. There was a good correlation between amount of toxin injected and amount of hemorrhage observed. Microscopically, hemorrhage was visible in all parts of the connective tissue surrounding muscle cells just 5 min after injection and fibrin was present both intravascularly and extravascularly. At later time periods the hemorrhage was more extensive and there was more fibrin. Many vessels were plugged with platelets. At 30 min after the injection, muscle cells appeared to be damaged having either delta lesions or disrupted myofibrils. Electron microscopy revealed damaged capillaries with ruptured endothelial cells, disrupted basal lamina and intact intercellular junctions. Thus, this hemorrhagic toxin acts rapidly to disrupt the capillary endothelium without damaging the intercellular junctions, and it also appears to damage skeletal muscle cells. PMID- 2219145 TI - A toxin profile for shellfish involved in an outbreak of paralytic shellfish poisoning in India. AB - Toxin profiles of clams and oysters involved in the outbreak of paralytic shellfish poisoning in India in 1983 were studied by a liquid chromatographic technique. Gonyautoxins 1, 2, 3, 4 and 8, and 11-epigonyautoxin 8 appeared to be the major toxins along with small amounts of saxitoxin, neosaxitoxin, decarbamoylsaxitoxin, decarbamoylgonyautoxins 2 and 3, C3 and C4. Toxin profile suggests the involvement of Alexandrium spp. in this outbreak. PMID- 2219146 TI - Renal disposition and nephrotoxicity of xenobiotics. Proceedings of the joint symposium of the Universities of Wurzburg and Rochester. Wurzburg, 7-10 October, 1990. PMID- 2219147 TI - Renal cell cultures: a tool for studying tubular function and nephrotoxicity. PMID- 2219148 TI - Nephrocarcinogenic xenobiotics. PMID- 2219149 TI - Nephrocarcinogenicity of estrogens. PMID- 2219150 TI - Perturbation of calcium homeostasis as a link between acute cell injury and carcinogenesis in the kidney. PMID- 2219151 TI - The role of damage and proliferation in renal carcinogenesis. PMID- 2219152 TI - Renal processing of glutathione conjugates by rat, chicken, pig and calf. PMID- 2219153 TI - Elimination of 14C by calves, pigs and rats renally perfused with radiolabelled dichlorovinyl or acetamide substrates. PMID- 2219154 TI - Cytotoxicity of 2-bromo-(N-acetylcystein-S-yl)-hydroquinone isomers in rat renal tubular epithelial cells. PMID- 2219155 TI - Effects of antioxidants and of different metabolic activation systems on dichlorovinylcysteine-induced genotoxicity. PMID- 2219156 TI - A 90-day study in rats with the monoglutathione conjugate of chlorothalonil. PMID- 2219157 TI - The activity of chromate reduction in renal tissue corresponds to chromate nephrotoxicity--developmental aspects. PMID- 2219158 TI - Primary cultures of rat and rabbit renal proximal epithelium as models for nephrotoxicity investigations. PMID- 2219159 TI - Transport and toxicity of CdCl2 in LLC-PK1 cells. PMID- 2219160 TI - Evidence of circadian variations in mercuric-chloride-induced proximal tubular necrosis by digital imaging microscopy. PMID- 2219161 TI - A 13C-NMR study on metabolic changes in proximal convoluted tubule cells induced by cadmium. PMID- 2219162 TI - Naproxen and indomethacin: disposition and effects in the isolated perfused rat kidney. PMID- 2219163 TI - A quantitative method for the measurement of urinary glycosaminoglycans- potential use in studies of xenobiotic nephrotoxicity. PMID- 2219164 TI - Peroxidative potential of suramin and effect on organic ion transport in rat kidney cortex. PMID- 2219165 TI - Renal tubular cell handling of digoxin and ouabain--in vitro study using LLC-PK1 cell lines. PMID- 2219166 TI - Gentamicin nephrotoxicity in rat renal proximal tubular cells. PMID- 2219167 TI - Netilmicin affects Na(+)-dependent D-glucose transport and the membrane fluidity of rabbit renal brush-border membrane vesicles: a comparison with gentamicin. PMID- 2219168 TI - Comparison of the renal response of male Fischer 344, Sprague-Dawley and Wistar rats to administration of gentamicin. PMID- 2219169 TI - Autacoid modulation and N-(3,5-dichlorophenyl)succinimide nephrotoxicity. PMID- 2219170 TI - Role of metabolic activation in the renal toxicity of carbon disulfide (CS2). PMID- 2219171 TI - Biochemical mechanisms of cephaloridine nephrotoxicity in suspensions of isolated rabbit proximal tubules. PMID- 2219172 TI - The avian renal portal system: a model for studying nephrotoxicity of xenobiotics. PMID- 2219173 TI - Involvement of tubular transport processes in nephrotoxicity. PMID- 2219174 TI - Cell culture in nephrotoxicity testing. PMID- 2219175 TI - Maintenance of glucose uptake in suspensions and cultures of human renal proximal tubular cells. PMID- 2219176 TI - Use of human proximal tubule cell cultures to study folate transport and binding. PMID- 2219177 TI - Protective effect of verapamil in cyclosporin-incubated isolated rat glomeruli. PMID- 2219178 TI - Potential contribution of lysosomal proteases to cyclosporine-A-induced nephrotoxicity. PMID- 2219179 TI - Human renal C-S lyases: two cytosolic isoenzymes. PMID- 2219180 TI - Human renal C-S lyase: structure-activity relationships of cytosolic and mitochondrial enzymes. PMID- 2219181 TI - Mercapturic acid formation in cultured opossum kidney cells. PMID- 2219182 TI - Transport of heavy metals by the kidney. PMID- 2219183 TI - Energy metabolism of the kidney: segmental differences may determine xenobiotic actions. PMID- 2219184 TI - Biochemical markers to monitor nephrotoxic effects in patients. PMID- 2219185 TI - Morphology of renal tubular damage from nephrotoxins. AB - The proximal renal tubular cells' vulnerability to the direct toxic action of chemicals is largely due to the role played by this nephron portion in absorption and secretion. This is an energy-demanding function so that these cells must have a high rate of oxidative metabolism and thus contain many mitochondria supplying the Na+/K+ pumps at the basolateral plasma membrane domain, thereby driving the carrier systems for entry of water and solutes across the luminal membrane. Thus toxic mechanisms leading directly or indirectly to disturbances of the renal cells' energy metabolism will result in cell injury and acute renal insufficiency. Quantitative morphological-stereological-analysis of at least two, the mercuric chloride- and the maleate-induced experimental models of toxic acute renal failure, show a very early substantial loss of ATP-generating mitochondrial inner membrane surface as well as substantial decrease in those functions protecting cells against oxidative or auto-oxidative processes, i.e. glutathione content, activities of the free-radical-scavenging systems superoxide dismutase, glutathione peroxidase and glutathione reductase and catalase. The cellular dysfunction following these early events may be considered as causative of the subsequent development of most of the morphological alterations described, which are fairly similar in appearance regardless of the toxic principle acting upon the kidney. PMID- 2219186 TI - Renal transport and metabolism of mercapturic acids and their precursors. PMID- 2219187 TI - Biosynthesis, bioactivation, and mutagenicity of S-conjugates. PMID- 2219188 TI - Mechanisms underlying cyclosporin A nephrotoxicity. PMID- 2219189 TI - Chronic nephrotoxicity of 2,2,4-trimethylpentane and other branched-chain hydrocarbons. PMID- 2219191 TI - Nephrotoxicity of metals: effects on plasma membrane function. PMID- 2219190 TI - Mechanisms of beta-lactam antibiotic nephrotoxicity. PMID- 2219192 TI - NMR: a tool for studying renal function and nephrotoxicity. PMID- 2219193 TI - Renal toxicity of antineoplastic agents. PMID- 2219194 TI - Susceptibility to toxic injury in different nephron cell populations. PMID- 2219195 TI - Electron microscopic identification and morphologic preservation of enriched populations of lung cells isolated by laser flow cytometry and cell sorting: a new technique. AB - There is increasing need to verify the identities of cell subpopulations enriched by laser flow cytometry and fluorescence-activated cell sorting (FACS). When cell subpopulations isolated from whole organs or tissues have similar characteristics (e.g., size, granularity, staining), light, phase contrast or fluorescence microscopy may not provide sufficient resolution to identify isolated cells accurately and many flow cytometric parameters (e.g., viability, fluorescence) require the cells to be live at the point of analysis where the cell transects the laser beam. In some studies, cells identified by fluorescence microscopy as a highly enriched subpopulation were found by electron microscopy to contain significant populations of other cell types. A technique, fixation-in-flow (FIF), has been developed to increase ability to correlate morphological and laser analyses of cell subpopulations. Sheath fluid is replaced by fixative, permitting fixation to be initiated immediately after laser beam analysis of live cells. This new procedure yields improved cytoarchitectural preservation of recovered cell subpopulation(s) for evaluation by transmission or scanning electron microscopy. This report presents results from applying the methodology to identify more accurately cell subpopulations of the distal lung, specifically type II pneumocytes, Clara cells and pulmonary macrophages. A modification of this procedure was employed to isolate fibroblast subpopulations from murine lung fibroblasts grown in vitro and the procedure is being used to determine the responses of cultured fibroblasts to other permutations (e.g., X-irradiation, cytokines). PMID- 2219196 TI - Induction and inhibition of estradiol hydroxylase activities in MCF-7 human breast cancer cells in culture. AB - The effects of estradiol, progesterone, and tamoxifen on the activity of estradiol 2- and 16 alpha-hydroxylases were studied in human breast cancer cell cultures using a radiometric assay. After 5 days' exposure to these compounds, incubations in the presence of either [2-3H]estradiol or [16 alpha-3H]estradiol as substrate were carried out. In MCF-7 cells, estradiol (10(-8) M), progesterone (10(-6) M) and tamoxifen (10(-6) M) significantly increased 16 alpha-hydroxylase activity (estradiol; 21% progesterone 10% to 32%; tamoxifen 21% to 31%; P less than 0.01). Synergistic effects were observed when the cells were successively exposed to tamoxifen and progesterone. Simultaneous treatment with tamoxifen plus estradiol or estradiol plus progesterone showed no change from estradiol alone. On the other hand, although estradiol had no direct effects on 2-hydroxylase activity, tamoxifen decreased this enzymatic activity significantly at 10(-6) M (23% to 37%). Progesterone acted synergistically to further decrease this reaction. Treatment with only progesterone caused an increase in 2-hydroxylation. In contrast, a subline of MCF-7 cells with low estrogen receptor levels showed only minimal enzyme-hormone responses. Likewise, treatment of the estrogen receptor-negative MDA-MB-231 human breast cancer cell line with these compounds showed no effects on either 2- or 16 alpha-hydroxylase activity. In the progesterone receptor-rich T47D cell line, estradiol decreased both activities while progesterone increased both.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2219197 TI - Synthesis of 7 alpha,12 alpha-dihydroxy-3 alpha- [2-(beta-D glucopyranosyl)acetyl]-5 beta-cholan-24-oic acid. AB - A C-glucoside of cholic acid was synthesized by the introduction of an acetyl group at position 3 alpha and direct one-pot C-glucosidation using 2,3,4,6-tetra O-benzyl-alpha-D-glucopyranosyl chloride. PMID- 2219199 TI - Monoclonal antibodies to pregnanediol-3-glucuronide: application to a direct enzyme-linked immunosorbent assay of urine. AB - Monoclonal antibodies to pregnanediol-3-glucuronide were produced and characterized. One of three clones investigated provided antibody suitable for a direct urinary enzyme-linked immunosorbent assay (ELISA). The ELISA uses a pregnanediol-thyroglobulin conjugate adsorbed onto the wells of a standard 96 well microtiter plate. Pregnanediol-3-glucuronide in standards or diluted urine competes with the immobilized steroid for antibody-binding sites. After washing, mouse monoclonal antibody bound to the plate is probed with antimouse immunoglobulin peroxidase. After further washing, o-phenylenediamine substrate is added and, finally, the absorbance is read at 492 nm. The ELISA shows excellent performance and agreement with the previous gas chromatographic method. The ELISA is ideal for aiding the assessment of ovarian function in the routine laboratory. PMID- 2219198 TI - Rapid transformation of [3H]cholesteryl ester in rat high-density lipoprotein: in vivo and in vitro studies. AB - [24,25-3H]Cholesteryl ester-labeled rat high-density and low-density lipoproteins were administered to recipient rats. Following death of the rats, a major portion of the radioactivity in administered [3H]cholesteryl ester-high-density lipoprotein rapidly appeared in less dense [3H]cholesteryl ester-lipoproteins and was isolated with the low-density lipoprotein fraction. The specific activity of the esterified cholesterol in the product lipoproteins found with the low-density lipoproteins exceeded that of the precursor high-density lipoproteins. In vitro, the addition of [3H]cholesteryl ester-high-density lipoprotein to plasma resulted in a five- to six-fold increase in radioactivity recovered in the low-density lipoprotein. These results demonstrate that, under a variety of experimental conditions, isolated high-density lipoprotein particles (both in vitro and in vivo) tend to become larger and less dense. Rapid changes in the density of lipoproteins labeled with [3H]cholesteryl ester must be considered when interpreting physiologic studies using this label. PMID- 2219201 TI - Determination of the affinity of a steroid for its receptor is not sufficient to measure its intrinsic hormonal activity. PMID- 2219200 TI - Sex steroid changes in porcine cystic ovarian disease. AB - Ten sex steroids were measured in the peripheral serum and ovarian follicular fluid of female pigs with or without cystic ovarian disease. In general, progestin, especially progesterone, accumulated excessively in the fluid contained in cystic compared with normal follicles. Nonluteinized cystic follicles contained up to four times the progesterone concentration found in large normal preovulatory follicles. Levels of this steroid increased with luteinization of cystic follicles to as much as 10 times those found in large preovulatory follicles. In contrast, the concentration of follicular fluid androgens and estrogens in cystic follicles were, at best, barely detectable (5 to 10 pg/ml). These results are indicative of a steroidogenic blockade in the conversion of C21 progestin to C19 androgens and C18 estrogens in the cystic follicles. In spite of an enormous accumulation of follicular progestin and subnormal concentration of androgens and estrogens, circulating levels of these hormones in pigs bearing cystic ovaries were in the normal range for cycling sows. Clearly, the hormonal abnormalities in the cystic follicles are not reflected in the serum profiles of these steroids. PMID- 2219202 TI - Stroke and its modification in Parkinson's disease. AB - Previous studies have not agreed on the incidence of ischemic stroke in persons with Parkinson's disease. There are epidemiologic and neurochemical facets of Parkinson's disease that might confer some benefit or protection against ischemic stroke. We used a case-control method to determine the lifetime history of ischemic stroke in 200 patients with Parkinson's disease and 200 controls of a similar age range. Analysis was also carried out for myocardial infarction as a marker of generalized atherosclerotic disease and for stroke risk factors. The cumulative incidence of ischemic stroke was significantly less in the patients with Parkinson's disease than in the controls, as was the cumulative incidence of myocardial infarction. Among risk factors, significantly fewer patients with Parkinson's disease used tobacco than controls. The decreased incidence of ischemic stroke in the patients with Parkinson's disease appears to be related to their less severe generalized atherosclerosis, possibly due to their lower incidence of tobacco use. In view of the known potential for dopamine to exacerbate experimental ischemic tissue damage, the possibility that the dopamine deficiency in the central nervous system of persons with Parkinson's disease confers an additional specific protective benefit against ischemic stroke cannot be excluded and requires further study. PMID- 2219203 TI - Hemodynamics in internal carotid artery occlusion examined by positron emission tomography. AB - Using positron emission tomography in nine patients with minor strokes, unilateral internal carotid artery occlusion, and good collateral circulation through the anterior portion of the circle of Willis, we analyzed regional cerebral blood flow, cerebral metabolic rate of oxygen, oxygen extraction fraction, and cerebral blood volume. These studies allowed quantification of the regional hemodynamic status, especially in relation to watershed areas. Compared with eight normal controls, the patients had significantly (p less than 0.01) decreased regional cerebral blood flow in the middle cerebral artery territory and the surrounding watershed areas of the occluded hemisphere. The oxygen extraction fraction rose with the distance from the anterior portion of the circle of Willis, attaining the highest value in the superior parietal and posterior temporo-occipital watershed area. A concomitant decrease in the cerebral blood flow/cerebral blood volume ratio suggested reduction in the mean blood flow velocity, whereby elevated blood viscosity would be more liable to reduce cerebral blood flow. These findings suggest hemodynamic vulnerability of the watershed areas after internal carotid artery occlusion in persons with good collateral circulation through the anterior portion of the circle of Willis. Our results also emphasize the importance of systemic hemodynamic factors such as blood pressure and circulating blood volume in the genesis of watershed infarction. PMID- 2219204 TI - Acute and long-term changes in serum lipids after acute stroke. AB - We studied serum lipid profiles in 171 patients less than or equal to 48 hours after the onset of acute stroke and 3 months later. The 83 patients suffering cerebral infarction had significantly higher serum concentrations of total cholesterol, low density lipoprotein-cholesterol, and apolipoprotein B and significantly lower serum concentrations of triglycerides and lipoprotein (a) less than or equal to 48 hours after ictus than 3 months later. The lipid profiles of the 53 patients suffering lacunar infarction were similar on both occasions, the only significant differences being higher total cholesterol and low density lipoprotein-cholesterol concentrations less than or equal to 48 hours after ictus. No significant changes were observed among the 35 patients suffering cerebral hemorrhage apart from a significantly higher concentration of high density lipoprotein3-cholesterol less than or equal to 48 hours after ictus. Our study, with many patients classified according to stroke subtype, gives results different from those of previous studies with much fewer patients. We conclude that in studies of serum lipid and lipoprotein concentrations as risk factors for cerebral infarction, comparing values obtained less than or equal to 48 hours after admission with control values may incorrectly identify certain lipid fractions as risk factors. PMID- 2219205 TI - Age-related spontaneous intracerebral hematoma in a German community. AB - We investigated incidence, age distribution in relation to etiology, and localization of spontaneous intracerebral hematoma in 100 consecutive cases. Incidence in the total population of the Giessen area was estimated to be greater than 11/100,000 inhabitants/yr and increased with age. There was a trend toward higher incidence in males. Overall mortality was 27%, 22% of 58 patients aged less than 70 years and 33% of 42 patients aged greater than or equal to 70 years. Hypertensive putaminal hematoma showed the highest mortality rate (42%, 10 of 24 cases). Chronic alcoholism and anticoagulant medication influenced the mortality rate unfavourably. We found the following localizations and etiologies to have a specific relation with age: 1) lobar hematomas from vascular malformations, group aged less than 40 years; 2) hypertensive putaminal hematomas and hypertensive thalamic hematomas, group aged 40-69 years; and 3) lobar hematomas, group aged greater than or equal to 70 years. Alcoholism was an additional factor in 38% of the 13 middle-aged men with hypertensive putaminal hematomas. Fourteen cases of spontaneous intracerebral hematoma were possibly due to cerebral amyloid angiopathy. Six of these 14 patients had recurrent lobar hematomas, but only three of the six could be histologically investigated. In these three cases, cerebral amyloid angiopathy was proven. PMID- 2219206 TI - Leukoaraiosis, intracerebral hemorrhage, and arterial hypertension. AB - To investigate whether the observed association of leukoaraiosis with intracerebral hemorrhage is direct or mediated by risk factors, we compared 116 patients with intracerebral hemorrhage confirmed by computed tomography and 155 controls without intracerebral hemorrhage, evaluating the prevalence of leukoaraiosis and vascular risk factors. Leukoaraiosis was observed in 21 (18%) of the 116 patients and in 12 (8%) of the 155 controls (p less than 0.01). Only two (6%) of the 31 patients with lobar hemorrhage had leukoaraiosis on computed tomograms, compared with 17 (24%) of the 71 patients with basal ganglionic hemorrhage (p less than 0.05). Leukoaraiosis was significantly correlated with intracerebral hemorrhage after controlling for age and sex by using multiple logistic regression analysis, while the correlation disappeared after controlling for hypertension. Our results indicate that leukoaraiosis is not an independent risk factor for intracerebral hemorrhage. PMID- 2219207 TI - Risk factors for white matter changes detected by magnetic resonance imaging in the elderly. AB - We found increased age (p = 0.001) and history or evidence of stroke (p = 0.016) to be significant independent multivariate predictors of the presence and severity of leukoencephalopathy on magnetic resonance imaging brain scans in a mixed population of 35 elderly psychiatric patients and 25 neurologically healthy elderly volunteers. These results suggest that subcortical ischemia, as well as age-related changes that may not be vascular in origin, contribute to the emergence of periventricular and other deep white matter hyperintensities that are commonly seen on the magnetic resonance imaging brain scans of older adults. PMID- 2219208 TI - A 21-aminosteroid reduces hydrogen peroxide generation by and chemiluminescence of stimulated human leukocytes. AB - Leukocytes recruited to regions of focal cerebral ischemia may contribute to tissue injury by their ability to promote inflammation. A novel group of drugs, the 21-aminosteroids, have been observed to reduce neurologic damage and vasogenic cerebral edema in animal models of stroke by inhibiting lipid peroxidation. Production of hydrogen peroxide and free radicals by leukocytes during the inflammatory response may contribute to lipid peroxidation and other consequences of free radical-mediated tissue injury. We assessed the effect of U74500A, a 21-aminosteroid, on the generation of hydrogen peroxide by and on the chemiluminescence of stimulated polymorphonuclear leukocytes and monocytes from normal humans. U74500A significantly reduced the generation of hydrogen peroxide by polymorphonuclear leukocytes (p less than 0.001) and monocytes (p less than 0.01) in a dose-dependent manner. Monocyte chemiluminescence was also significantly inhibited (p less than 0.05), but polymorphonuclear leukocyte associated chemiluminescence was unchanged. Our results indicate that U74500A can reduce the concentration of oxygen metabolites associated with stimulated human leukocytes, and this effect may explain in part how 21-aminosteroids reduce lipid peroxidation, ischemic injury, and vasogenic edema. PMID- 2219209 TI - Cerebral blood flow in experimental ischemia assessed by 19F magnetic resonance spectroscopy in cats. AB - We evaluated a 19F magnetic resonance spectroscopic technique that detects Freon 23 washout as a means of measuring cerebral blood flow in halothane-anesthetized adult cats during and after transient cerebral ischemia produced by vascular occlusion. The experiments were performed to test the ability of this recently developed method to detect postischemic flow deficits. Results were consistent with postischemic hypoperfusion. The method also proved valuable for measuring small residual flow during vascular occlusion. Our experiments indicate that this method provides simple, rapid, and repeatable flow measurements that can augment magnetic resonance examinations of cerebral metabolic parameters in the study of ischemia. PMID- 2219210 TI - Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits. AB - Platelet-activating factor is a potent mediator of inflammation, which has untoward effects on cerebrovascular and neural elements. While several investigators have reported attenuation of ischemic damage after treatment with antagonists of platelet-activating factor, no study has proved endogenous production of platelet-activating factor in ischemia of the central nervous system. We hypothesized that endogenous production of platelet-activating factor participates in the early pathologic manifestations of deteriorating stroke. In 12 rabbits, we found tissue levels of platelet-activating factor measured by the release of serotonin from washed platelets to be elevated by approximately 20 fold in spinal cord injured by 25 minutes of ischemia and 2 hours of reperfusion (2.80 +/- 0.98 ng/g) compared with that in normal spinal cord (0.15 +/- 0.06 ng/g, p less than 0.01). Given during ischemia to seven rabbits, 10 mg/kg i.p. of a highly selective and potent antagonist of platelet-activating factor (BN 50739) accentuated the early postischemic hyperemia and prevented the delayed hypoperfusion measured by on-line laser-Doppler flowmetry (-35 +/- 7% of baseline [n = 7] without versus 33 +/- 14% with treatment, p less than 0.01) and the edema formation measured as the increase in tissue water content (4.4 +/- 0.7% without [n = 6] versus 2.1 +/- 0.6% with [n = 7]treatment, p less than 0.05) after 2 hours of reperfusion. This neurochemical and pharmacologic evidence emphasizes a new perspective of ischemia-induced phospholipid degradation and suggests an important role for platelet-activating factor in the early manifestations of stroke. PMID- 2219212 TI - Diurnal variation of cerebral blood flow in rat hippocampus. AB - We measured local cerebral blood flow over 24 hours in 10 unanesthetized, freely moving rats to determine whether blood flow in the hippocampus fluctuated as a function of time of day. We measured hydrogen clearance at 1-hour intervals using a polyurethane-coated platinum electrode with a 1-mm bare tip implanted in the dorsal hippocampus. Individual rats displayed a wide range of local cerebral blood flow values (from 30 to 100 ml/min/100 g tissue) in a day. In seven of the 10 rats, the overall mean hippocampal blood flow for the dark cycle (7 PM-5 AM) was significantly (p less than 0.001, 0.01, or 0.05) greater than that for the light cycle (6 AM-6 PM), showing an average increase of 20%. Further, the maximum mean hippocampal blood flow at 11 PM in all 10 rats was 42% greater than the minimum at noon. Our study demonstrates for the first time that local cerebral blood flow in the hippocampus shows diurnal variation. PMID- 2219211 TI - Beneficial effect of 1,3-butanediol on cerebral energy metabolism and edema following brain embolization in rats. AB - We assessed the effect of 1,3-butanediol on cerebral energy metabolism and edema after inducing multifocal brain infarcts in 108 rats by the intracarotid injection of 50-microns carbonized microspheres. An ethanol dimer that induces systemic ketosis, 25 mmol/kg i.p. butanediol was injected every 3 hours to produce a sustained increase in the plasma level of beta-hydroxybutyrate. Treatment significantly attenuated ischemia-induced metabolic changes by increasing the concentrations of phosphocreatine, adenosine triphosphate, and glycogen and by reducing the concentrations of pyruvate and lactate. Lactate concentration 2, 6, and 12 hours after embolization decreased by 13%, 44%, and 46%, respectively. Brain water content increased from 78.63% in six unembolized rats to 80.93% in 12 saline-treated and 79.57% in seven butanediol-treated rats 12 hours after embolization. (p less than 0.05). The decrease in water content was associated with significant decreases in the concentrations of sodium and chloride. The antiedema effect of butanediol could not be explained by an osmotic mechanism since equimolar doses of urea or ethanol were ineffective. Our results support the hypothesis that the beneficial effect of butanediol is mediated through cerebral utilization of ketone bodies arising from butanediol metabolism, reducing the rate of glycolysis and the deleterious accumulation of lactic acid during ischemia. PMID- 2219213 TI - Pharmacologic irreversible narrowing in chronic cerebrovasospasm in rabbits is associated with functional damage. AB - We studied isolated basilar artery segments from a rabbit model of chronic cerebrovasospasm. Autologous blood placed around the basilar artery of rabbits killed 1, 2, 3, 4, 5, 6, 7, or 9 days later caused narrowing of the segments with a biphasic time course. The first (immediate) phase was reversed by intra arterial papaverine; the second phase exhibited an increasing component of narrowing that was papaverine-insensitive. Based on the passive force/length curves, basilar artery segments became increasingly stiff over 9 days. By contrast, the segments' contractility decreased. Responses of the basilar artery segments were greater over the first few days, but then became less than that of saline-injected controls. Contractions in response to norepinephrine and potassium were reduced. Endothelium-based acetylcholine-induced vasodilation progressively diminished, as did the response to sympathetic nerve stimulation. There was a negative correlation between artery wall stiffness and contractility. The papaverine-insensitive component of angiographic narrowing correlated directly with loss of contractility and with artery wall stiffness. These results are consistent with the conclusion that increased artery wall stiffness is a primary determining factor in the arterial narrowing of chronic cerebrovasospasm. PMID- 2219214 TI - Progressive shrinkage of the thalamus following middle cerebral artery occlusion in rats. AB - Permanent middle cerebral artery occlusion in rats results in infarction in the ipsilateral cortex and caudate nucleus-putamen. In this ischemia model, severe shrinkage of the ipsilateral half of the thalamus was observed several months after surgery. We examined the serial profile of this phenomenon in 40 rats at intervals from 2 weeks to 6 months after the operation. The area of the ipsilateral half of the thalamus as a percentage of the area of the contralateral half was 87% at 2 weeks, 77% at 1 month, 54% at 3 months, and 54% at 6 months. Such severe morphologic change distant from the original ischemic focus has not been reported in models of experimental focal ischemia. Retrograde degeneration is thought to play an important role in this phenomenon. PMID- 2219215 TI - Therapeutic window of CA1 neuronal damage defined by an ultrashort-acting barbiturate after brain ischemia in gerbils. AB - Previous therapeutic studies on the prevention of selective vulnerability of neurons in the hippocampus have suggested that the critical period for induction of delayed neuronal injury occurs early during recirculation. To determine the onset and duration of this period, an ultrashort-acting barbiturate (methohexital) was infused into the left carotid artery of 47 gerbils after various times of recirculation following 10 minutes of bilateral forebrain ischemia. Neuronal density in the left CA1 sector was determined 7 days later by counting the number of surviving neurons per millimeter of pyramidal cell layer. In 16 saline-treated gerbils, less than 10% of the CA1 neurons survived the 10 minutes of ischemia. Postischemic carotid infusion of methohexital improved neuronal survival, the degree of improvement depending on the timing and duration of the methohexital infusion. When carried out during the initial 40 minutes of recirculation, methohexital infusion for 10 minutes increased the number of surviving neurons to approximately 60% of that in five sham-operated control gerbils. This increase was significant for infusions carried out between the 10th and 20th minutes (n = 6, p less than 0.05) and between the 30th and 40th minutes (n = 6, p less than 0.05) of recirculation. Methohexital infusion for 20 minutes increased neuronal survival to 95% and 73% of that in the controls when carried out between the 0th and 20th minutes (n = 5, p less than 0.005) and between the 20th and 40th minutes (n = 5, p less than 0.005) of recirculation, respectively. Protection was nonsignificant for 10- or 20-minute methohexital infusions carried out after the 40th minute of recirculation. Our results demonstrate that the pathologic processes leading to delayed neuronal injury in the CA1 sector are induced during the initial 40 minutes of recirculation and that barbiturates are able to reverse these processes only if given during this period. PMID- 2219216 TI - Retinal infarction during sleep and wakefulness. AB - Brain and retinal infarctions during sleep have been attributed to focal hypoperfusion caused by systemic hypotension combined with underlying arterial stenosis, rather than to embolism. Because some retinal emboli may be visualized on ophthalmoscopy, we studied 24 consecutive patients (18 men and six women) aged 26-78 (mean 58) years with recent retinal infarction and determined whether the infarction had occurred during sleep or wakefulness. All patients underwent dilated ophthalmoscopy and a carotid artery study (arteriography in 20, duplex ultrasound in the remaining four), and 12 had echocardiography. Retinal infarction occurred during sleep at an unexpectedly rate (14 of 24 observed compared with eight of 24 expected, p = 0.02). Retinal cholesterol emboli were seen in one half of the patients regardless of whether the retinal infarction had occurred during sleep or wakefulness. Carotid artery disease was found in seven of the 14 patients in whom infarction had occurred during sleep and in eight of the 10 patients in whom infarction had occurred during wakefulness (p = 0.21). Cerebrovascular occlusive disease was not found in the five patients aged less than 50 years. Our findings suggest that embolism is a common mechanism of retinal infarction during sleep or wakefulness, that in patients aged greater than 50 years extracranial carotid artery disease is a common source of retinal emboli, and that the retina may be especially susceptible to infarction during sleep. PMID- 2219217 TI - Etiologic importance of the intimal flap of the external carotid artery in the development of postcarotid endarterectomy stroke. AB - A technically unsatisfactory end point (transition from the removed diseased plaque to normal distal intima) leading to an intimal flap of the external carotid artery has been identified as a source of perioperative stroke. The mechanism involves thrombus formation with retrograde propagation of the thrombus and subsequent embolization of the internal carotid artery. This report describes three cases illustrating this mechanism and methods of identification and correction. This mechanism of postoperative stroke adds further justification for the routine use of intraoperative surveillance studies to document the technical result of endarterectomy involving the internal and external carotid arteries. When an unsatisfactory end point is identified in the external carotid artery, it should be corrected with the same sense of concern as a similar finding in the internal carotid artery. PMID- 2219218 TI - Cerebral venous thrombosis due to heparin-induced thrombocytopenia. AB - A patient with polycythemia vera who was treated with heparin for superficial septic thrombophlebitis developed heparin-induced thrombocytopenia and cerebral venous thrombosis with superior sagittal sinus occlusion 11 days after the institution of heparin therapy. We suggest that the severe thrombotic response to the heparin-induced platelet disorder in this patient occurred because the polycythemia vera and the purulent infection enhanced the thrombophilia caused by heparin-induced thrombocytopenia. This condition can be avoided in most instances if heparin is used for no longer than 5 days. PMID- 2219219 TI - Two cases of spontaneous internal carotid artery occlusion due to giant intracranial carotid artery aneurysm. AB - Although spontaneous thrombosis of a giant intracranial aneurysm is relatively common, occlusion of its parent artery is rare. We describe two recent patients in whom the parent artery spontaneously occluded. One patient had severe stenosis of the left internal carotid artery, with delayed appearance of a faint shadow of vascular widening near the posterior clinoid process. One month later, complete occlusion of the left internal carotid artery was shown angiographically. The second patient had dysarthria and left hemiparesis, resulting in the diagnosis of a left internal carotid artery giant aneurysm. He had suffered an episode of visual disturbance of the right eye 5 years before. Angiography showed the right cervical internal carotid artery to be occluded. We believe the mechanism of parent artery occlusion in our two patients to be due first to stretching of the internal carotid artery by the enlarged aneurysm, followed by compression of the internal carotid artery by the aneurysm itself. Next, the anterior clinoid process and the optic nerve are involved, and, finally, thrombosis of the aneurysmal cavity extends into the internal carotid artery itself. PMID- 2219221 TI - Sneddon's syndrome with negative antiphospholipid antibodies. PMID- 2219220 TI - Coexistence of cystatin C and beta protein immunoreactivity. PMID- 2219222 TI - Detection of middle cerebral emboli during coronary artery bypass surgery using transcranial Doppler sonography. PMID- 2219223 TI - Effect of intra-aortic balloon pumps on cerebral circulation. PMID- 2219224 TI - Maternal-child health and family planning: user perspectives and service constraints in rural Bangladesh. AB - This article presents a microanalysis of interactions between female fieldworkers and women in rural Bangladesh, and a discussion of the broader organizational constraints that hamper service delivery. It is argued that the fieldworker, herself a rural woman, is faced with considerable demand for both maternal-child health (MCH) and reproductive health care services, but that operational constraints prevent her from realizing her potential in both of these areas. Qualitative data show that, in the eyes of rural women, contraceptive use and health care are intricately intertwined, and that this association often raises a range of questions that the worker cannot address competently. A number of specific operational barriers--worker densities, staff motivation, supervision, technical competence, supplies--are identified. These barriers reflect a general institutional weakness in the Ministry of Health bureaucracy that prevents it from organizing itself to deliver user-oriented health and family planning services while maintaining adequate and appropriate standards of care. PMID- 2219225 TI - Pregnancy termination and the law in Nigeria. AB - Abortion in Nigeria is illegal and carries a heavy jail sentence--up to 14 years imprisonment--unless it is performed to save the life of the pregnant woman. Nevertheless, a large number of clandestine abortions continue to be carried out regularly, often with dire consequences for the lives and health of the women involved. This article reviews abortion legislation in Nigeria, examines court decisions on the subject, and presents the results of a survey conducted on the incidence of abortion in the country. A case is made for revising existing abortion laws. A brief look is taken at the various indications for abortion that might be adopted and a proposal is made for a new abortion policy in Nigeria in the light of the country's recently adopted population policy. PMID- 2219226 TI - Fertility intentions and subsequent behavior: a longitudinal study in rural India. AB - This report compares fertility and family planning intentions of rural Indian women in 1975 with actual outcomes in 1987. Ninety-four of 103 respondents who had fewer children than they wanted in 1975 and had stated definite intentions with respect to future fertility and contraceptive use were reinterviewed in 1987. Overall, women had fewer children than desired and stopped childbearing when they reached or closely approximated their ideal number of sons. Since sons were clearly the determinant of "reproductive success," it is argued that only a significant change in the status of rural women can bring about widespread compliance with the official family planning program's two-child norm. PMID- 2219227 TI - Toward consistency in breastfeeding definitions. AB - On 28 April 1988, the Interagency Group for Action on Breastfeeding met to develop and agree upon a set of definitions that could be used as standardized terminology for the collection and description of cross-sectional information on breastfeeding behavior. The schema and potential framework suggested at the meeting were reviewed extensively by breastfeeding researchers and program personnel, revised at subsequent meetings by a variety of organizations, and compared against published research on patterns of breastfeeding and their effects on infant nutrition, health, and fertility. This schema and framework: (1) acknowledge that the term "breastfeeding" alone is insufficient to describe the numerous types of breastfeeding behavior, (2) distinguish full from partial breastfeeding, (3) subdivide full breastfeeding into categories of exclusive and almost exclusive breastfeeding, (4) differentiate among levels of partial breastfeeding, and (5) recognize that there can be token breastfeeding with little to no nutritional impact. The schema and framework should assist researchers and agencies in their efforts to accurately describe and interpret breastfeeding practices. PMID- 2219230 TI - Xenophobia, T cells and a journey to a foreign land. PMID- 2219228 TI - Observations on abortion in Zambia. AB - This report describes the findings of a preliminary investigation of women who sought treatment for abortion from the Gynecological Emergency Ward at the University Teaching Hospital (UTH) in Lusaka, Zambia. Barriers to obtaining legal abortions are identified and the harsh experiences of women seeking treatment for complications of illegally induced abortion are discussed. The data contribute to an understanding of the intensity of abortion for Zambian women and draw attention to the value of small-scale, qualitative research on women's reproductive health care needs. It is suggested that a study be planned at UTH to determine how health care delivery can be improved for women who seek abortion. PMID- 2219229 TI - Ghana 1988: results from the Demographic and Health Survey. PMID- 2219232 TI - Serum concentrations of IgM, IgG1, IgG2b, IgG3 and IgA in C57BL/6 mice and their congenics at the nu(nude)locus. AB - The absolute concentrations of IgM, IgG1, IgG2b, IgG3 and IgA were determined in mice of C57BL/6 background, from weaning to one year of age, by quantitative isotype-specific, indirect double sandwich ELISAs. The comparison of 10-40 weeks old athymic nude C57BL/6 females with age matched females of the wild strain showed a general decrease of the whole serum Ig levels in the athymic mice, which was however contributed quite differently by the different Ig isotypes: a significant decrease (about 3.5 fold) was found for IgG2b only (0.34 mg/ml), whereas 1.5 fold more IgM (0.28 mg/ml) and about 2 fold more IgG3 (0.27 mg/ml) were detected, the IgG1 (0.19 mg/ml) and IgA (0.07 mg/ml) levels remaining within the normal range ! Limited data for IgG2a suggest that that this isotype may also be decreased in nude mice (0.36 mg/ml) in comparison with normal B6 + mice (0.54 mg/ml). Thus, although homozygosity at the nu locus results in a lack of effector T cells, our data show, at the humoral level, a limited degree of thymus dependence of an Ig isotype. It is intriguing that, although thymus dependence of several Ig isotypes looked evident ten years ago in early studies on nude mice, more recent data are very variable and controversial in this respect. PMID- 2219231 TI - Characterization of lymphatic and venous emigrants from the thymus. AB - Lymphocytes leaving the thymus via two different pathways were examined as to their morphology and phenotype. Cells leaving the thymus via lymphatics were obtained by a direct cannulation of thymic lymphatics and those leaving via the thymic vein were labelled within the thymus using an extracorporeal perfusion system and identified subsequently as fluorescent cells in the draining vein. In both cases the cervical thymus in lambs was used, since it is located in the neck region and ensures easy access to both blood and lymphatic vessels of the thymus without subjecting the animal to a major trauma or stress. Cells obtained from the thymic lymphatics or lymphatic emigrants were found to have distinct features different from peripheral T cells in terms of their surface morphology and expression of the MHC antigens. Venous emigrants were also slightly different from peripheral T cells in MHC expression. Estimation on the rate of thymocyte emigration into the periphery suggested that neither venous nor lymphatic emigrants represent a major fraction of de novo synthesized cells in the thymus of this animal species, as has been suggested in the mouse. PMID- 2219233 TI - Enzyme-histochemical profile of macrophages in the rat thymus after the application of cyclophosphamide. PMID- 2219234 TI - Abnormal thymocyte subpopulations in split dose irradiated C57BL/Ka mice before the onset of lymphomas. Effects of bone marrow grafting. AB - Fractionated whole-body X irradiation (4 x 1.75 Gy at weekly intervals) induces a high percentage of thymic lymphomas in C57BL/Ka mice. The present work reports the phenotypic alterations of thymocyte subpopulations during the preleukemic period: there were a decrease of CD4+ CD8+ cells and an increase of CD4- CD8- and CD4- CD8+ cells. Marrow grafting early after irradiation that prevents lymphoma development restores the thymocyte subpopulations. In many instances, transplantation of 'preleukemic thymocyte inoculate' gives rise to an active and long lasting repopulation of recipient thymuses. However in all cases, donor lymphomas can develop after inoculation of 'preleukemic thymocyte inoculate'. PMID- 2219235 TI - [Detection of memory impairment using a recognition test for words and faces]. AB - Fifty-two patients (mean age 78.3; sd: 5.5; range 70-94) who were admitted to psychogeriatric day care because of memory problems and other cognitive deficits were tested with the Dutch form of Warrington's Recognition Memory Test (RMT). Forty-five mentally normal elderly (mean age 79.5; sd: 5.7; range 69-92) were also tested in order to establish the sensitivity and specificity of the test for the detection of memory impairment. Mentally normal subjects were mainly recruited from homes for the aged and were rated by the staff as free from any symptoms of dementia or other psychiatric disease. Using cut-off scores at the 98%-specificity level, the sensitivity of the RMT was 54% for the verbal part (Recognition Memory for Words, RMW) and 73% for the non-verbal part (Recognition Memory for Faces, RMF). Selection of cut-off scores with high sensitivity (96%) resulted in specificities of 62% and 71% for RMW and RMF, respectively. The RMF appears to be a more valid test for the detection of memory impairment than the RMW. Selection of cut-off scores is contingent on knowledge of the pretest or prior probability of memory impairment. A cut-off score with high sensitivity is recommended if impairment is strongly suspected, whereas high specificity is needed to verify the presence of impairments for which there is little clinical evidence. PMID- 2219236 TI - [Loneliness among the frail elderly and possibilities for intervention by primary care caregivers. Report of an inventory study in 2 Amsterdam neighborhoods]. AB - In Amsterdam in 1987 an inventory was drawn up of factors that practitioners (n = 39) and volunteers (n = 22) associated with loneliness among the elderly. Three groups of non-institutionalized old elderly (80 years and older) served as respondents (total n = 100). Some of the factors that the helpers mentioned, such as reported health problems, not having children and dissatisfaction with housing conditions are actually found to be related to loneliness. Other factors such as gender, marital status and the presence of children, relatives and friends in the neighbourhood had no association with loneliness. Although not all the factors mentioned were related to loneliness, when practitioners assumed an older person to be lonely, their assessment was rather correct. Practitioners and volunteers claimed to use a broad scale of interventions where loneliness was concerned. Their help varied from practical to psycho-geriatric care. Clients often did not recognize such help as being directed at their loneliness. We refer to this as 'latent' help. The effectiveness of interventions for loneliness can be enhanced by more openness in the helping situation. Moreover the success of interventions seemed to be thwarted by reluctance on the part of helpers to be more critical about their own behaviour. Improvement of social contacts is not the only way to help the alleviation of feelings of loneliness among the oldest old. Emphasizing the merits of nonsocial activities can be an additional way to help. PMID- 2219237 TI - [Incidence, risk and operability of abdominal aortic aneurysm in the elderly patient]. AB - The risks of operative treatment of abdominal aortic aneurysm are considerably smaller in elective circumstances than after rupture of the aneurysm. The risk of a ruptured aneurysm is higher than the indicated percentage in the literature, because this only reflects the operative mortality. Possibly almost 65% of the patients with a rupture of an abdominal aortic aneurysm die at home or during transport to the hospital. In the absence of valid contra-indications to surgery, elective operative treatment should be considered, also in the elderly patient. PMID- 2219239 TI - [Pneumonia in the elderly]. AB - In the aged, pneumonia is associated with considerable morbidity and mortality. As a consequence of ageing, decreased mobility, underlying illnesses and medication, especially the host defense mechanisms in the respiratory tract may become deficient. The kind of micro-organism that causes the infection depends on whether the patient lives at home or whether he is institutionalised (nursing home, skilled nursing facility, hospital). Pneumonia in patients at home is mainly caused by pneumococci, whereas in institutionalised patients also other micro-organisms, especially Gram-negative bacteria are the cause. The diagnosis is often difficult due to the lack of symptoms and signs in the aged patient. An important sign is tachypnea. For the choice of anti-microbial therapy the question whether the patient acquired the infection at home or in an institution is crucial, as is the question, whether the patient has recently used anti microbial drugs. Finally, therapy differs in patients that produce sputum and in those who do not. PMID- 2219238 TI - [Drug treatment of cancer in elderly patients]. AB - Cancer is a disease predominantly seen in the older age group. The most frequent forms are in males: lung, prostatic, stomach, colonic and bladder cancer. In females: breast, colonic, stomach cancer, lymphoma, leukaemia and rectal cancer. In view of the expected demographic figures a dramatic increase in the incidence of cancer is expected. The malignancies seen in the elderly respond generally poor to chemotherapy. Most cytotoxic drugs are excreted by the kidneys. Especially the renal clearance of anticancer drugs will therefore be compromised in the elderly, this should be considered when giving cytostatics. Mucositis, bone marrow toxicity, pulmonary and neurotoxicity are quite often enhanced in the older patient group. The indications for chemotherapy are limited. Chemotherapy should not be withheld from patients with advanced breast cancer and certain haematological malignancies. Further clinical research focussed on the elderly is warranted. Drugs with a mild spectrum of side effects deserve priority. Hormonal treatment is an important modality in breast, prostatic and endometrial carcinoma. The burden for the patients is limited and the advantages are well documented. PMID- 2219240 TI - Break it off. Identifying a destructive love relationship. AB - 1. Destructive love is an active process of destroying the affection and tenderness between two people. 2. If people are unable to distinguish the difference between an argument that was formulated to clear up a misunderstanding from an argument that is destructive, they will be unable to function properly. 3. Five basic therapeutic elements needed for recovery are: a willingness to seek help; a move toward a more realistic form of thinking; spirituality in one's personal and professional life; a circle of friends who support emotional honesty; and a personal appreciation of one's own values instead of the values of a past partner. PMID- 2219241 TI - Face value: trends and advances in craniofacial surgery. AB - 1. The ability of a computerized tomography scan to project a three-dimensional reconstruction of the patient's skeleton allows surgeons to plan the reconstructive process preoperatively. 2. Because of the length of the procedure, patient positioning, cardiorespiratory status, and laboratory values are essential. 3. It is beneficial to perform craniofacial surgery at early ages while there is still growth potential and before the skin and muscles have tightened. PMID- 2219243 TI - Draping: how much and which one? PMID- 2219242 TI - Nip it in the bud. Controlling wound infection with preoperative shaving. AB - 1. Postoperative wound sepsis can double the normal patient hospital stay and significantly add to the cost of hospitalization. Close skin shaving prior to surgery (especially if done the night prior to surgery) is a contributing factor to postoperative wound sepsis rates. 2. This problem can be managed by selecting a preoperative shaving technique that rids the skin surface of hair, soils, and microorganisms, but still leaves the epidermal layer intact as a natural barrier against opportunistic microorganisms. 3. Hair removal at the surgical site is not the cause of postoperative wound sepsis. Preoperative techniques that remove hair shafts and not epidermal layers are important in managing this problem in the operating room. PMID- 2219244 TI - How to detect if the balloon bursts. PMID- 2219246 TI - Interferon: a cure for hepatitis B. PMID- 2219245 TI - Anxiety related to impending surgery. PMID- 2219247 TI - Winds of change. PMID- 2219248 TI - Pancreatoduodenectomy: a complicated solution. AB - 1. Pancreatoduodenectomy is an effective operative procedure for benign large tumors and cancers of the pancreas and periampullary sites and extensive trauma to these areas. 2. Pancreatoduodenectomy may be performed in two stages: total excision of pancreas, subtotal excision, and pyloric exclusion procedures. 3. Carcinoma of the proximal pancreas is a serious medicosurgical problem, and radical pancreatoduodenectomy is the most effective form of therapy. 4. Pancreatoduodenectomy is a major operative procedure with serious intraoperative and postoperative complications that are directly related to the experience of the surgeon. PMID- 2219249 TI - Severe and complicated malaria. World Health Organization, Division of Control of Tropical Diseases. PMID- 2219250 TI - Cloning the ABH genes. PMID- 2219251 TI - Control of red cell production: the roles of programmed cell death (apoptosis) and erythropoietin. PMID- 2219252 TI - Routinely washing irradiated red cells before transfusion seems unwarranted. PMID- 2219253 TI - Prenatal identification of potential donors for umbilical cord blood transplantation for Fanconi anemia. AB - Reported here are studies of Fanconi anemia fetal cells that led to the first use of umbilical cord blood for hematopoietic reconstitution in a clinical trial. Prenatal diagnosis and HLA typing were performed in fetuses at risk for Fanconi anemia (FA) to identify, prior to birth, those that were unaffected with the syndrome and were HLA-identical to affected siblings. Umbilical cord blood was harvested at the delivery of these infants; assays of progenitor cells indicated the presence of colony-forming units-granulocyte-macrophage (CFU-GM) in numbers similar to those of bone marrow CFU-GM that are associated with successful engraftment in HLA-matched allogeneic bone marrow transplantation. The possibility that umbilical cord blood from a single individual can be used as an alternative to bone marrow for hematopoietic reconstitution has now been demonstrated by the successful engraftment of two patients with FA. Progenitor cell assays of umbilical cord blood collected at the birth of a child affected with FA, who had been misdiagnosed on the basis of chorionic villus sampling (CVS) studies, indicated a profound deficiency in colony formation, consistent with previously reported abnormalities in the growth of FA cells in vitro. These results suggest that the hematopoietic disorder in FA is related to an underlying problem with cell proliferation. PMID- 2219254 TI - The differentiation of delayed serologic and delayed hemolytic transfusion reactions: incidence, long-term serologic findings, and clinical significance. AB - Delayed serologic transfusion reactions (DSTRs) and delayed hemolytic transfusion reactions (DHTRs) were studied in a large tertiary-care hospital. A DSTR was defined by the posttransfusion finding of a positive direct antiglobulin test (DAT) and a newly developed alloantibody specificity. A DHTR was defined as a DSTR case that showed clinical and/or laboratory evidence of hemolysis. Thirty four cases of DSTR, 70 percent of which were due to anti-E and/or -Jka, were documented prospectively over a 20-month period. Retrospective review of the medical records found clinical evidence of hemolysis in only 6 (18%) of the 34. Thus, the incidence of DSTR was 1 (0.66%) of 151 recipients with posttransfusion samples available for testing, whereas the incidence of DHTR was only 1 (0.12%) of 854 patients tested. Fifteen of the 34 patients were followed for up to 174 days after reaction. Twelve of the 15 still demonstrated a positive DAT with anti IgG only. Eluate studies indicated that the persistence of a positive DAT after DSTR or DHTR may involve several immunologic mechanisms, including the development of posttransfusion autoantibodies. This study indicates 1) that DSTRs are a frequent finding in multiply transfused patients, although most cases are benign and fail to meet rigid criteria for DHTR, and 2) that the persistence of a positive DAT after DSTR or DHTR is common. PMID- 2219255 TI - Detection of drug-dependent, platelet-reactive antibodies by antigen-capture ELISA and flow cytometry. AB - The effectiveness of flow cytometry in the detection of drug-dependent, platelet reactive antibodies was investigated. In studies of seven sera known to contain quinine- or quinidine-dependent, platelet-reactive antibodies, flow cytometry was 5 to 10 times more sensitive in detecting drug-dependent antibodies (DDAbs) than the 51Cr release assay, antigen-capture enzyme-linked immunosorbent assay (ELISA), and indirect immunofluorescence microscopic assay. With flow cytometry, DDAbs could be detected at drug concentrations as low as 0.1 microM, or less than one-tenth the level required with other methods. Antigen-capture ELISA was not as sensitive as flow cytometry in DDAb detection, but it did allow identification of the DDAbs' target molecules. With this assay, five of the seven DDAbs recognized both the glycoprotein Ib/IX (GPIb/IX) and glycoprotein IIb/IIIa (GPIIb/IIIa) complexes, while the remaining two sera reacted only with GPIb/IX. Of 44 consecutive patients who developed thrombocytopenia while taking quinidine, DDAbs were detected by flow cytometry in 11 (25%), more than twice the number detected by other methods. In one patient who developed thrombocytopenia while taking trimethoprim/sulfamethoxazole, DDAbs could be detected only by flow cytometry. It can be concluded that flow cytometry is highly sensitive in detecting DDAbs and allows their detection at pharmacologic concentrations of the drug. Most quinidine-dependent antibodies recognize at least two different glycoprotein complexes in the platelet membrane. PMID- 2219256 TI - Incubation of platelet concentrates before transfusion does not improve posttransfusion recovery. AB - Incubation of stored platelet concentrates (PCs) at 37 degrees C for 1 hour has been reported to result in a better morphology score and improved platelet recovery. A study was conducted in adult patients with leukemia to determine whether incubation of stored PCs results in an improved platelet recovery as measured by 10-minute posttransfusion corrected count increments (CCI). Eligible patients had platelet counts of less than 30,000 per microL and were clinically stable. Patients were transfused with 6 to 10 units of PC stored for 3 days (15 studies) or 4 days (5 studies). Platelets were pooled and then split in two equal volumes so that each patient received two sequential half-transfusions, one incubated at 37 degrees C for 1 hour and the other kept at 22 degrees C for 1 hour. Patients were randomized as to which half-transfusion was received first. The mean CCI of the incubated half-transfusions was 13.6 x 10(3) when they were given first and 14.5 x 10(3) when given second; this was not significantly different from the mean CCI of the nonincubated half-transfusions: 13.8 x 10(3) when they were given first and 13.8 x 10(3) when given second. In contrast to earlier reports, it can be concluded that incubation of pooled PCs does not improve platelet recovery. PMID- 2219257 TI - A study of confidential unit exclusion. AB - The effectiveness of the confidential unit exclusion (CUE) procedure recommended by the Food and Drug Administration has been questioned by the blood banking community. The purpose of this study was to determine whether donors were informing the blood center correctly regarding the disposition (transfuse or do not transfuse) of their donated blood. A letter explaining the confidential study and requesting permission to send the participant a questionnaire noting his or her self-exclusion choice was mailed to 230 donors who had chosen transfuse and 276 donors who had chosen do not transfuse. After consent was obtained, participants were sent a second packet and asked to indicate whether they had chosen correctly and, if not, to identify reasons for that incorrect choice. A seven-word terminology quiz made up of words from the CUE form was also enclosed. All participants who had chosen transfuse indicated that this was the correct choice. Approximately 50 percent of those who had chosen do not transfuse indicated that this was an incorrect choice; the most common reason was that "I was not paying attention." The most frequently misunderstood term was "confidential." Donors who chose do not transfuse had a significantly higher rate of error on the terminology quiz (p less than 0.01) than did those who chose transfuse. PMID- 2219259 TI - Red cell autoantibodies, multiple immunoglobulin classes, and autoimmune hemolysis. AB - The effects and interrelationships of multiple immunoglobulin coating (i.e., increased red cell [RBC]-bound IgM and/or IgA in addition to IgG) were investigated in 404 patients with warm-reactive RBC autoantibodies on 590 occasions. Multiple immunoglobulins were detected by enzyme-linked direct antiglobulin tests in 218 samples (37%), but in only 87 (15%) by agglutination methods. Differences in populations were examined by chi-square, with p less than 0.005 being required for significance because of the multiple tests. Compared with IgG coating alone, multiple immunoglobulins were significantly associated with larger quantities (greater than 800 molecules/RBC) of IgG, multiple IgG subclasses, IgG3 and C3d bound to the cells, and with serum haptoglobin levels of less than 0.1 g per L. The latter association was still significant when higher levels of RBC-bound IgG and subclass pattern were taken into account. In samples with multiple immunoglobulin coating, there was no significant relationship (p greater than 0.05) between haptoglobins of less than 0.1 g per L and either C3d or multiple IgG subclasses. It was concluded that multiple immunoglobulin coating, even when undetected by agglutination methods, is a major cause of hemolysis: it is part of a more generalized autoimmune response and acts with other factors such as the quantity of bound IgG, the IgG subclass pattern, and complement; it also has an important hemolytic effect in its own right. PMID- 2219260 TI - In vivo viability and functional integrity of filtered platelets. AB - The in vivo viability and functional integrity of filtered platelets were compared with those of nonfiltered platelets in a controlled study. On two occasions, after template bleeding time, 14 healthy volunteers underwent plateletpheresis and received 600 mg of aspirin. Autologous 111In-labeled platelets were transfused without further manipulation (control) on one occasion and after filtration on a second occasion. The filter was primed and flushed with a buffered 12.6-percent solution of ACD-A in 0.9-percent normal saline (pH 6.5). After transfusion, the bleeding time was measured at 1, 4, and 24 hours and platelet survival at 10 minutes; 1, 4, and 24 hours; and daily for 6 days. The decrease in the bleeding time was not significantly different from that after transfusion of nonfiltered platelets (p greater than 0.2). Filtering of platelets did not affect 1-hour in vivo recovery (filtered, 69.5%; nonfiltered, 66%: p = 0.56) or the platelet survival (filtered platelet t1/2 = 83.0 hours, nonfiltered platelet t1/2 = 82.9 hours: p = 0.96). It can be concluded that filtration does not adversely affect in vivo recovery, survival, or functional integrity of platelets. PMID- 2219258 TI - Effects of blood donation on cerebral blood flow velocity. AB - Eighteen healthy male blood donors, nine with hematocrit (Hct) of 0.40 to 0.45 (normal Hct) and nine with Hct of 0.49 to 0.52 (upper-limit Hct), were monitored by continuous-wave internal carotid Doppler sonography and hematologic tests for 28 days after blood donation, to ascertain whether and to what extent a single standard donation may modify the velocity of cerebral blood flow. The two groups had similar mean predonation values of internal carotid flow velocity (ICFV): blood donation was followed in both groups by a slight, transient decrease of ICFV at the end of phlebotomy, due to donation-induced hypovolemia, and then by an increase of ICFV lasting 7 to 10 days. Analysis of individual profiles revealed that only four of nine upper-limit and six of nine normal Hct donors displayed a positive trend (increase) in the ICFV within the first week after donation, and that it was due mainly to a rise in systolic flow velocity. Mean Hct and arterial oxygen content showed a negative trend (decrease) within the first week that was opposite to the ICFV trend. Other laboratory variables, including serum proteins and plasma fibrinogen concentration, and the iron status indicators did not change, except for serum ferritin, which also decreased within the first week after phlebotomy. It can be concluded that blood donation may result in a short-term increase of blood flow velocity that is independent of Hct predonation levels in approximately one-half of the donors. PMID- 2219261 TI - Abnormal membrane physical properties of red cells in McLeod syndrome. AB - McLeod red cells (RBCs) lack Kx antigens and have weak expression of the Kell antigens. Individuals who carry the McLeod phenotype have acanthocytic RBCs and a compensated hemolytic state. To elucidate the role of the protein on which the Kx antigens reside in maintaining membrane deformability, the rheologic properties of McLeod RBCs were determined by ektacytometry. RBCs were obtained from normal individuals and from four patients with McLeod syndrome. Osmotic gradient deformability profiles of McLeod RBCs showed decreased whole cell deformability. Resealed ghosts from McLeod RBCs also showed decreased deformability, partly because of the decreased cell surface area and partly because of an intrinsic membrane stiffness in this syndrome. For the measurement of membrane mechanical stability, resealed ghosts were subjected to constant high shear stress in the ektacytomer, and deformability was recorded continuously as the deformable ghosts fragmented into rigid spherical vesicles. Membranes from McLeod RBCs showed a noticeable increase in mechanical stability. Acquired causes of acanthocytosis, such as liver disease, did not cause the rheologic abnormalities observed in McLeod cells. Other abnormalities noted in McLeod RBCs were decreased RBC potassium content and an increased number of dense RBCs, as determined by centrifugation on a discontinuous density gradient. The data indicate that McLeod RBCs are rigid and have decreased surface area and that their membranes are intrinsically rigid with increased mechanical stability. These abnormalities may account for the reduced RBC survival observed in McLeod syndrome. The protein that carries the Kx surface antigen seems to be required for the maintenance of the normal physical function of RBC skeletal proteins. PMID- 2219262 TI - Clinical significance of white cell antibodies in febrile nonhemolytic transfusion reactions. AB - Febrile nonhemolytic transfusion reactions (FNHTRs) are associated with white cell (WBC) antibodies. The purposes of this study were to determine the frequency of WBC antibodies, to associate the severity of reactions with antibody specificity, and to distinguish FNHTRs from infection and postoperative fever. By using the granulocyte indirect immunofluorescence test in conjunction with lymphocytotoxicity testing, it was found that 70 percent of FNHTRs in 24 patients involved WBC antibodies. The remaining 30 percent of apparent FNHTRs were associated with infections and postoperative fever. Granulocyte-specific antibodies were as prevalent as HLA antibodies and were associated with the severest reactions. Because FNHTRs occur with granulocyte-specific antibodies, HLA antibodies, and possible monocyte-specific antibodies (untested in this and other studies), these reactions could be grouped together as WBC-associated reactions. PMID- 2219263 TI - Autoimmune hemolytic anemia in Kawasaki disease: a case report. AB - A 3-year-old boy presented with the fever, conjunctivitis, rash, and lymphadenopathy diagnostic of Kawasaki disease. Treatment with antibiotics, aspirin, and intravenous immunoglobulin was instituted. The hematocrit decreased from 35 percent on admission to 11 percent by hospital Day 10, and the white cell count had increased from 13.7 to 42 x 10(3) per microL, and the patient had a leukoerythroblastic blood smear. The direct antiglobulin test demonstrated IgG but not complement on the red cell (RBC) surface. An acid eluate reacted (titer of 4) with all panel cells in the antiglobulin phase. Intravenous immunoglobulin from the same lot used for treatment did not contain antibody that reacted with the patient's group O RBCs or a panel of group O RBCs, but did contain IgG anti-A and -B (titer of 4). The patient received a transfusion and was given methylprednisone. The direct antiglobulin test and acid eluate were negative 4 days later. The patient had an uneventful recovery. The distinction between antibody-mediated hemolytic anemia and autoimmune hemolytic anemia is important in the treatment of this disease. PMID- 2219264 TI - Fibrin glue: the perfect operative sealant? PMID- 2219265 TI - Febrile reactions in platelet transfusion recipients. PMID- 2219266 TI - An unexpected effect of polyethylene glycol on the specificity of monoclonal anti B. PMID- 2219267 TI - Risks of plasticizers in blood bags. PMID- 2219268 TI - Use of polyethylene glycol in the blood bank. PMID- 2219269 TI - The role of endothelial cells in inflammation. PMID- 2219270 TI - The mechanism of synergistic interaction between anti-interleukin 2 receptor monoclonal antibody and cyclosporine therapy in rat recipients of organ allografts. AB - Untreated anephric LEW rats die ca. 9 days following transplantation of LBNF1 kidney allografts. Although treatment with ART-18, a mouse antirat IL-2R mAb (300 micrograms/kg/day x 10 days), prolonged graft survival to ca. 3 weeks, the severely impaired renal function was comparable to untreated controls (creatinine levels 3-5 mg/dl). In contrast, simultaneous infusion of ART-18 and a very low dose of CsA (0.75 mg/kg x 10 days), marginally effective on its own, resulted in survival of greater than 45 days; the grafts exhibited relatively good function comparable to that in rats treated with full-dose (15 mg/kg/day) CsA. This beneficial biological effect did not depend upon elevated CsA trough levels in animals conditioned with both modalities. The CD4:CD8 ratio at the graft site was lowest (0.3-0.4) in recipients treated with ART-18 + CsA. Synergy between the two agents has been demonstrated by adoptive transfer studies in which nonspecific suppression has been conferred selectively by cells infiltrating kidney grafts in rats given ART-18 and CsA in concert but not separately (LBNF1 and WF test cardiac allograft survival ca. 12 days). In contrast, suppression in the recipient spleens was donor-specific; both CD4 and CD8 cells prolonged test graft survival. Immunohistological evaluation of renal allografts revealed that therapy with ART-18 or low-dose CsA alone failed to deplete IL-2R+ cells and prevent production of IL-2, IFN-g, and TNF. In contrast, the frequency of infiltrating IL 2R+ cells and elaboration of endogenous cytokines in non-uremic hosts receiving combination therapy was greatly depressed, stressing again synergistic interaction between ART-18 and CsA. Additionally, markedly reduced class II antigen induction, XL-fibrin deposition, and glomerulitis may also contribute to prolonged survival and satisfactory function of kidney allografts in this animal group. PMID- 2219271 TI - Short-term effects of cyclosporine on secretagogue-induced insulin release by isolated islets. AB - Brief exposure (30 min) of isolated islets to 0.5 microgram/ml cyclosporine leads to alterations in the insulin secretory response to selected stimuli. When glucose is used as the secretagogue, cyclosporine slightly stimulates insulin release at substimulatory concentrations of the hexose. The inhibitory effect predominates, however, at stimulatory concentrations of glucose with a threshold at 6 mmol/L glucose and maximal inhibition of 33.5 mmol/L glucose. By contrast, insulin release induced by 17 mmol/L arginine is not affected. Cyclosporine also inhibits by 66% the insulin secretory response to 100 nmol/L phorbol 12-myristate 13-acetate, suggesting that either cyclosporine interferes with phorbol ester action on beta cells or the action site is located beyond the protein kinase C activation. On the other hand ionomycin-stimulated insulin response is also blocked by cyclosporine, indicating that insulin release induced by transient changes in cytosolic Ca++ is also affected. The evidence gathered here suggests that the inhibitory effect of cyclosporine on insulin release is apparent when glucose is used as a fuel stimulant and is reversed following removal of the stimulant. This effect is not reversed by using substances known to activate the protein kinase C or the Ca(++)-dependent branches of the stimulus-secretion coupling system in beta cells, indicating that the site of action of cyclosporine on pancreatic islets might be located in distal steps of the stimulus-secretion coupling of glucose-induced insulin release. PMID- 2219272 TI - Cardiac transplantation in the rat. II. Alteration of the severity of donor graft arteriosclerosis by modulation of the host immune response. AB - Cardiac transplantation between inbred rat strains that differ for weak histocompatibility antigens is associated with the development of arteriosclerosis in the arteries of the donor graft myocardium. The lesions are seen in donor/recipient pairs that differ for both MHC and non-MHC histocompatibility antigens that apparently stimulate a low-level, chronic rejection of the donor heart graft. The arteriosclerosis associated with this chronic rejection consists of a diffuse, concentric proliferation of the intima and pathologically resembles the lesions observed in the coronary arteries of long-term human cardiac graft recipients. We have recently examined the influence of positive and negative manipulation of the host immune response on the development of the graft arteriosclerosis. Our results demonstrate that delayed harvest of the cardiac grafts or immunization with donor skin grafts or splenic lymphocytes increases the sensitivity of the recipient to the donor heart grafts- and, under conditions that allow for the long-term survival of the graft- increases the severity of the arteriosclerotic lesions. Alternatively, suppression of the host immune responses with cyclosporine or FK506, substantially reduces the arteriosclerotic changes. These results suggest that control of accelerated graft arteriosclerosis in long-term human cardiac recipient may require more careful and effective immunosuppression of the allograft reaction. PMID- 2219273 TI - Modulation of experimental cyclosporine nephrotoxicity by inhibition of thromboxane synthesis. AB - The clinical usefulness of Cyclosporine is limited by its intrinsic nephrotoxicity. A potential mechanism of CsA-mediated renal injury may involve an alteration in the prostaglandin-thromboxane (PG-TX) cascade. In our studies, pharmacological manipulation of the PG-TX system in normal and nephrotoxic animals was conducted using a specific thromboxane synthetase inhibitor U63,557A, and the cyclooxygenase inhibitor indomethacin. Administration of CsA 50 mg/kg/day for 7 days to Sprague Dawley rats resulted in a 99% increase in urinary thromboxane B2 excretion compared with controls (48.2 +/- 3.1 vs. 24.2 +/- 2.6 ng/24 hr, P less than 0.001), while plasma levels remained unchanged. Glomerular and tubular function was significantly reduced at this time, with a 48% decrease in creatinine clearance (CCr), and a 25% reduction in the fractional excretion of sodium (FeNa) (P less than 0.001). Histological injury included cortical tubular vacuolization and necrosis. Administration of indomethacin 8 mg/kg/day to both normal and CsA-treated rats resulted in a significant reduction in prostanoid excretion. Indomethacin alone had no adverse effect on glomerular function; however, when coadministered with CsA an exaggerated decrease in renal function was observed. CCr in this group fell by a further 27% compared with the CsA-50 group, while FeNa decreased by 76% (P less than 0.001). Histologic injury intensified, with an increase in vacuolization and necrosis. In contrast, coadministration of U63,557A with CsA prevented the rise in urinary TXB2 excretion, improved CCr by 20% (P less than 0.05), and restored FeNa to control levels. The severity of CsA-induced vacuolization was significantly diminished. Selective inhibition of thromboxane production may therefore be valuable in mitigating the clinical nephrotoxicity of CsA. PMID- 2219274 TI - Hemodynamic and biochemical changes during normothermic and hypothermic sanguinous perfusion of the porcine hepatic graft. AB - Using an ex vivo liver sanguinous perfusion system, hemodynamic and biochemical changes of the porcine livers were studied, which were preserved cold (4 degrees C) for 24 hr in University of Wisconsin solution and reperfused with normothermic (37 degrees C) (n = 8) or hypothermic (32 degrees C) (n = 8) blood for 3 hr. Six more livers were reperfused with normothermic blood (37 degrees C) immediately after procurement as controls. The total hepatic blood flow was adjusted to 1 ml/min/g liver weight, in which hepatic artery and portal vein flows were administered at a 1:2 ratio. In livers stored cold for 24 hr in UW solution and perfused normothermically, a statistically higher hepatic artery resistance was exhibited at 30 and 60 min after reperfusion (P less than 0.05), and there was lower bile output (P less than 0.05) at 90 and 120 min as compared to the controls. In livers stored cold for 24 hr in UW solution and perfused hypothermically, as compared to ones perfused normothermically, statistically higher hepatic-artery and portal-vein resistances (P less than 0.05) were observed throughout the perfusion period and 60 min after reperfusion, respectively. In addition, bile output and oxygen consumption of these livers were statistically lower than those of ones perfused normothermically (P less than 0.05). In contrast, chemistries of the perfusate of livers perfused hypothermically were comparable to ones perfused normothermically. Histologic examination of the liver perfused hypothermically demonstrated hepatic arterial and/or portal venous congestion and mild-to-moderate hemorrhage in the portal triads. This study suggests that livers preserved for a prolonged period of time demonstrate a high hepatic arterial resistance shortly after revascularization, and that recipient hypothermia after revascularization may be a risk factor for the development of hepatic arterial thrombosis following liver transplantation. PMID- 2219275 TI - Cellular proliferation at the site of organ allografts and the influence of immunosuppressive therapy. AB - In this study we investigated cellular proliferation of T cells and macrophages at the site of rat cardiac allografts and determined the influence of immunosuppressive therapy on the proliferative characteristics of these cell types. A bromodeoxyuridine-labeling technique was used that allowed both the accurate detection of proliferative activity and the phenotypic characterization of cellular infiltrates within grafted tissues. In untreated recipients (BN--- Lewis), T cytotoxic/suppressor cells as well as T helper cells showed proliferative activity at the site of the graft. The percentage of OX8-positive cells within the graft that showed proliferation ranged from 15% to 37%. The percentage of W3/25-positive cells within the graft that showed proliferation ranged from 25% to 30%. In contrast, macrophages hardly showed proliferative activity within the graft; only 1-4% of the macrophages stained positive for bromodeoxyuridine. From these observations it is concluded that the graft serves as a nonlymphoid tissue site, wherein lymphocytes can freely proliferate and expand. To study the influence of immunosuppressive therapy on cellular proliferation, the steroid budesonide, 120 micrograms/kg/day, was administered for 13 days (MST, 20 days). During effective immunosuppressive therapy, still a remarkable amount of infiltrating cells was present within the grafts. Moreover, immunosuppressive treatment did not primarily appear to affect the proliferative capacity of the individual cell types. OX8-positive cells as well as W3/25 positive cells clearly showed proliferative activity within the treated grafts. However, despite the presence of these proliferative cells, signs of graft destruction were absent during immunosuppressive therapy. This finding may shed new light on the effect of steroids at the site of the graft and their role in the prevention of tissue destruction. PMID- 2219276 TI - Examination of the role of the impermeants lactobionate and raffinose in a modified UW solution. AB - Rat liver transplants were performed in order to assess the importance of the impermeant anion lactobionate and the trisaccharide raffinose on the effectiveness of a simplified variant of UW solution for liver preservation by simple cold storage. Rat livers were stored at 4 degrees C for 18, 24, 30, or 40 hr in a modified UW solution or in one of three variants of UW in which one of these impermeants was replaced by another more permeable agent. Using modified UW solution (solution A), 50% (5/10) of rats receiving livers that had been preserved for 30 hr survived for more than 1 week; with solution B, which differs from A in the replacement of raffinose by glucose, the 1-week survival was 60% (6/10) after 30-hr preservation. Solution C, which is identical to A except for the replacement of lactobionate by gluconate, gave 20% (2/10) survival rate after 30-hr preservation. However, using solution D, which is identical to A except for substitution of chloride for lactobionate, none (0/8) of the rats receiving liver preserved for 30 hr survived. These results suggest that the inclusion of lactobionate as a major anion plays a crucial role in the effectiveness of UW solution, whereas raffinose can be replaced by more permeant glucose without deleterious effect. PMID- 2219277 TI - Canine pancreas and kidney transplantation following total-lymphoid irradiation. AB - The effect of total-lymphoid irradiation on survival of canine pancreas and kidney allografts was studied. TLI had a marked immunosuppressive effect as measured by in vitro immune responses and reduced circulating leukocytes. Despite the changes, median graft survival times for animals treated with 800 cGy (9 days) or 1800 cGy (9.5 days) were not significantly different from untreated control animals (7 days). The addition of low-dose antithymocyte globulin (10 mg/kg/day) on post-transplant days 0, 2, 4, 6, 8, and 10 had no measurable synergistic effect. Similarly, median segmental pancreas allograft survival times after 1700-2200 cGy of TLI treatment (16.5 days) were only marginally longer than those of untreated controls (9 days). The only animal to maintain a graft for greater than 200 days was matched to the donor in mixed lymphocyte culture (MLC). This animal was able to reject a third-party skin graft after 8 days while a graft from the original donor was still surviving after 21 days when the pancreas graft failed from a chronic-type rejection. These results indicate that TLI alone or in combination with ATG will not be predictably effective as a method of prolonging allograft survival. The role of matching major histocompatibility complex antigens in TLI treatment requires clarification. PMID- 2219278 TI - Function of kidney grafts from brain-dead donor pigs. The influence of dopamine and triiodothyronine. AB - There are conflicting reports about the effects of administration of dopamine to brain-dead donors upon posttransplant organ function. This study compared the survival and serum creatinine levels in pigs that received renal grafts from untreated controls, from controls in which either the donor or donor and recipient received dopamine or from animals rendered brain dead for 16 hr by acute elevation of intracranial pressure, and given standard supportive treatment. In two additional groups, brain-dead donors were given dopamine or dopamine with triiodothyronine. Recipients of grafts from control animals or from brain-dead donors survived the 7-day period of study and showed minimal changes in serum creatinine. Recipients of grafts from brain-dead donors given dopamine however showed reduced survival and progressive increase in serum creatinine. This did not occur in the group given triiodothyronine concurrently with dopamine. It is suggested that if administration of dopamine is essential to treat donor hypotension, concurrent use of triiodothyronine may preserve posttransplant renal function. PMID- 2219279 TI - Correlation between class II antigen (DR) expression and interleukin-2-induced lymphocyte proliferation during acute cardiac allograft rejection. AB - We have previously reported a correlation between biopsy-proven rejection and the presence of IL-2-responsive lymphocytes for biopsy specimens from human cardiac allografts. We thus hypothesized a relationship between tissue expression of HLA class II antigen (DR) and the outgrowth of IL-2-responsive lymphocytes. Employing immunofluorescence DR staining with a propidium iodide counterstain in consecutive specimens from 41 patients, we found two patterns of DR expression: DR expressed on the vascular endothelial surface (donor antigens) and/or on myocardial infiltrating cells (presumably recipient antigens). Specimens were categorized by histologic diagnosis as "baseline nonrejecting controls" that were obtained 7.5 +/- 0.4 (mean +/- SE) days posttransplantation, "nonrejecting" (obtained 59.9 +/- 5.8 days posttransplantation), "prerejecting" (obtained 47.7 +/- 6.3 days posttransplantation), and "rejecting" (obtained 101.3 +/- 10.1 days posttransplantation). Prerejecting specimens were histologically negative specimens obtained from patients a mean of 6.0 +/- 0.4 days before a biopsy proven rejection episode. The percentage of specimens positive for interstitial DR staining were: less than 1% for controls, 30% for nonrejecting specimens, 68% for prerejecting, and 46% for rejecting. For vascular DR staining, 25% of control specimens were positive, 56% of nonrejecting, 74% of prerejecting, and 73% of rejecting specimens. Culture positivity was seen for 38% of controls, 35% of nonrejecting specimens, 79% of prerejecting, and 70% of rejecting. Vascular DR staining was higher than interstitial staining for all specimen categories. For the vascular pattern, the mean score was significantly higher for culture positive specimens compared to culture negative (0.87 +/- 0.1 vs. 0.59 +/- 0.1; P less than 0.01). A similar relationship was not found for the interstitial pattern. Lymphocyte growth occurred in conjunction with vascular DR upregulation significantly more frequently than in conjunction with interstitial DR expression (65% vs. 35% of culture-positive specimens, P less than 0.0001). These findings suggest a relationship between DR expression, lymphocyte growth, and acute rejection. Vascular DR and interstitial DR patterns show several differences with respect to kinetics of expression and correlation with histology and culture, and thus may represent different processes. PMID- 2219280 TI - Cyclosporine nephrotoxicity in cardiac allograft patients--a seven-year follow up. AB - Renal function was observed retrospectively in a population of 228 adults who underwent a cardiac allograft at the University of Pittsburgh from June 1980 through June 1987, survived a minimum of one year, and received cyclosporine. Renal function was determined by serial measurement of serum creatinine concentration. Serum creatinine rose from 1.2 +/- 0.0 mg/dl at time of hospital discharge to 2.0 +/- 0.0 mg/dl at two and four years and 3.3 +/- 0.1 mg/dl at seven years. The fall in renal function was biphasic, with a rapid decline (reciprocal creatinine slope -0.018 dl/mg-mo) through 24 months and a slower decline thereafter -0.0036 dl/mg/month). This occurred despite a progressive decrease in cyclosporine levels from 668 +/- 23 ng/ml (whole blood RIA) to 380 +/ 12 ng/ml at seven years. Three of 222 patients (1.6%) developed end-stage renal disease within 18 months of initiation of cyclosporine therapy. Only one additional patient of 26 followed through 54 months (3.8%) developed end-stage disease thereafter. The decline in renal function seen with cyclosporine is rapid in the first 18 months, with a slower but continuing decline seen with later follow up. At least in heart transplantation, the risk of end-stage renal disease is significant, but not prohibitive. PMID- 2219281 TI - The recurrence of focal segmental glomerulosclerosis in kidney transplant patients treated with cyclosporine. AB - To evaluate the rate of recurrence of focal segmental glomerulosclerosis (FSGS) in renal transplant patients treated with cyclosporine, we reviewed the outcome of 25 renal Tx performed in 24 patients who had FSGS as their original renal disease. After Tx, 6 patients were treated with steroids and azathioprine (follow up: 42 +/- 34 months) and 19 with CsA (follow-up: 30 +/- 31 months). Two of 6 Aza treated patients (33%) developed recurrence of FSGS and nephrotic syndrome (NS). Both patients lost their graft because of FSGS 24 and 25 months after Tx. Ten of 19 patients (55%) given CsA showed recurrence of FSGS; one of them had had recurrence in the first graft treated with Aza. One patient lost his graft a few weeks after Tx because of acute rejection and 3 lost their graft because of FSGS 4-28 months after NS developed. One patient with NS died from pneumonia 14 months after Tx when his plasma creatinine was 2.7 mg/dl. Three other patients now have NS and plasma creatinine between 1.9 and 2.4 mg/dl 15-37 months after Tx. The last two patients have NS and normal renal function 10 and 31 months after Tx. In both groups, most patients developed NS within the first week after Tx. The patients with recurrence, given Aza or CsA, tended to be younger at the onset of the disease and to have a shorter duration of the disease, when compared with those without recurrence, but the differences were not statistically significant. In our experience neither CsA nor Aza showed any effect on the outcome of FSGS recurring in the graft. PMID- 2219282 TI - Successful use of rifampicin in the treatment of tuberculosis in renal transplant patients immunosuppressed with cyclosporine. AB - Cyclosporine and rifampicin were used simultaneously in 6 renal transplant patients with tuberculosis. The total daily dose of cyclosporine had to be increased 3-5 fold, with the frequency of administration increased from twice to thrice daily. With this regimen, satisfactory cyclosporine levels were attained and there was no adverse affect on graft function. PMID- 2219284 TI - Multiple site estimates of erythropoietin and renin in polycythemic kidney transplant patients. AB - The development of polycythemia after renal transplantation is a well known phenomenon and its etiology remains controversial. In particular, it is unknown whether inappropriate erythropoietin (EPO) production could be a reason. Utilizing a sensitive radioimmunoassay for EPO we have measured EPO concentrations in venous blood from native and grafted kidneys in three normocythemic and seven polycythemic patients. We found that (1) in our posttransplantation polycythemic patients there are inappropriately high systemic EPO levels, hence that posttransplantation polycythemia is related to EPO overproduction. (2) This high EPO production comes from the native kidneys. (3) There is a correlation between EPO and renin levels in the peripheral as well as in native and transplanted kidneys' venous samples. PMID- 2219283 TI - The impact of HLA matching on graft survival and on sensitization after a failed transplant--evidence that failure of poorly matched renal transplants does not result in increased sensitization. AB - There are costs (both financial and ethical) to distributing kidneys by HLA-match (time, transportation, repeat crossmatch; possibly bypassing a more deserving recipient). Arguments favoring matching include better short- and long-term survival, and decreased panel-reactive antibody (PRA) if a well-matched vs. poorly matched transplant fails. We studied these phenomena in a single institution. Since 1970, 1329 patients received cadaver (CAD) transplants; for those with defined antigens (n = 1316) there was no difference in 10-year graft survival in those with a less than or equal to 1 AB match vs. those with greater than 1 AB match or those with less than or equal to 1 AB mismatch (mm) vs. greater than 1 AB mm. Similarly there was no difference in those with less than or equal to 2 BDR mm vs. greater than 2 BDR mm. In fact, those with less than ABDR mm had worse 10-year graft survival (55%) than those with greater than or equal to 3 ABDR mm (61%) (P = .001). For patients with function greater than 6 months there was no difference in long-term outcome based on HLA match or mm. These findings were similar for patients both with and without CsA immunosuppression, and for primary and retransplants. A total of 382 patients transplanted since 1980 have lost their grafts (146 died with function). All had received pretransplant transfusions. Of 236 alive after graft loss, 64 had no postgraft failure PRAs (22 out of state, 23 chose to remain on dialysis, 19 died less than 3 months after graft loss); 172 had PRAs after failure; 106 (62%) have been retransplanted. Mean peak PRA in those retransplanted was 23 +/- 31 (range 0 100) vs. 46 +/- 39 (range 0-100) in those not retransplanted (P less than .05). Patients were stratified by PRA prior to first transplant (0%, 1-20%, greater than 20%). For recipients with 0% PRA, failure of a CAD transplant (n = 58) was no more likely to result in an increase of PRA than failure of a living-related donor (LRD) transplant (n = 49) (NS). For those with an increase, mean increase was 45% +/- 34 after LRD transplant and 41% +/- 28 after CAD transplant (NS). The proportion developing PRA greater than or equal to 60% was not different after a failed LRD (7/49) or CAD (11/58) transplant (NS). Other subgroups had similar results. AZA or CsA immunosuppression did not affect development of increased PRA after a failed graft.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2219285 TI - Bone marrow transplantation for the Wiskott-Aldrich syndrome. Long-term follow up. AB - Wiskott-Aldrich Syndrome (WAS) is a sex-linked disease characterized by immunodeficiency and thrombocytopenia. Supportive treatment of this disease is inadequate and bone marrow transplantation has been reported to result in excellent survival. The long-term follow-up of 8 male patients who received bone marrow transplantation for the WAS is reported here. All of these patients received ablative preparative treatment consisting of ATS (antithymocyte serum), cytoxan and either busulfan or TBI (total body irradiation). Bone marrow was transplanted from an HLA-matched donor. Seven of eight of these male patients have had excellent engraftment of their transplant and now have adequate lymphocyte and platelet function. In addition, they have had good growth and development. This suggests that ablative preparative treatment followed by early bone marrow transplantation from an HLA-matched donor is a highly successful therapy for this congenital disease. PMID- 2219286 TI - Subclinical hepatic encephalopathy. Comparison before and after orthotopic liver transplantation. AB - Sixty-two patients were evaluated before and after liver transplantation on a battery of neuropsychologic tests measuring hepatic encephalopathy. Compared to controls, deficits were found on tasks measuring memory and visuospatial capacity prior to transplantation. Most of these deficits were ameliorated following the surgery. It is concluded that functional psychological capacity is restored to a large extent, but not completely, following orthotopic liver transplantation. PMID- 2219287 TI - Effects of sex steroid hormones on sex-associated differences in the survival time of allogeneic skin grafts in rats. Evidence that testosterone enhances and estradiol reverses the immunosuppressive activity of cyclosporine. AB - Three-week-old DA (RT1a) male and female rats were pretreated with either orchiectomy or ovariectomy and administration of the opposite-sex steroid hormones, estradiol or testosterone. Skin from same-sex AO (RT1a) rats was then grafted when these pretreated rats reached 14 weeks of age, with a short course of immunosuppressive treatment of cyclosporine. The survival times of the grafts were reversed in that the male recipients pretreated to be like females acutely rejected the graft within 10 days as do normal adult female recipients. On the other hand, the female recipients pretreated to be like males accepted the graft as do normal adult male recipients. In addition, the synergistic effects of either testosterone or estradiol with CsA on the survival time of the graft were examined. Testosterone successfully prolonged graft survival on normal adult female and young male recipients, but negligible prolongation was observed on young females. In contrast, estradiol abrogated the immunosuppressive activity of CsA and accelerated graft rejection in both male and female recipients. PMID- 2219288 TI - Cyclosporine-induced tolerance to intratesticular islet xenografts. AB - Survival of highly immunogenic hamster islet xenografts can be achieved in rats if the graft is transplanted into the abdominal testis. Permanent survival requires the administration of cyclosporine during the first thirty days after grafting. The majority of grafts will survive indefinitely beyond this point if the grafted animals receive a once-weekly maintenance dose of CsA until day 100, when CsA is no longer necessary. Hamster islet xenografts transplanted under the kidney capsule or into the portal vein are rejected, regardless of CsA treatment. Animals maintaining long-term primary intratesticular xenografts accept secondary contralateral testicular xenografts. CsA is not required. Primary grafts are also resistant to the adoptive transfer of lymphocytes from rat donors primed to hamster xenoantigens. Secondary hepatic and renal islet xenograft survival is also extended--some hepatic grafts long-term. Therefore, the combination of CsA and the privileged status of the abdominal testis leads not only to the acceptance of primary intratesticular islet xenografts but also to partial immunological unresponsiveness of subsequent grafts in other sites. PMID- 2219289 TI - Dissociation of tissue destruction induced by cytolytic T cells in vivo and cytotoxicity as measured in vitro. AB - Two forms of local cutaneous graft-versus-host reactions were used to examine the in vivo activity of cytolytic T cells in a large number of antigen systems and mouse strain combinations. In immune lymphocyte transfer reactions (TrRs), CTL were injected intradermally into allogeneic hosts to which they were sensitized; in bystander reactions (ByRs), CTL were mixed with target cells and the mixture injected into hosts syngeneic to the CTL. Both reactions frequently culminate in full-thickness skin destruction. However, CTL highly active in cell-mediated lympholysis assays in vitro sometimes failed to induce significant reactions in vivo, and CTL with negligible CML activity often induced severe, necrotizing lesions. In addition, Clone 58, a non-MHC-specific CD8+ clone that originated from cells extracted from a sponge matrix allograft, lost its CML activity but continued to induce necrotizing TrRs and ByRs. Insofar as these reactions may exemplify the specific (TrR) and nonspecific (ByR) tissue injury that occurs in the rejection process, these findings question the reliability of CML for predicting the ability of CTL to induce the tissue destruction seen in allograft rejection. PMID- 2219291 TI - Specific suppression of allograft rejection by soluble class I antigen and complexes with monoclonal antibody. AB - In this experiment, we investigated the effect of daily injection or continuous slow infusion of either DA (MHC haplotype, RT1a) serum or soluble DA class 1 MHC antigen or its complexes with monoclonal antibody on rejection of heterotopic heart allograft in the combination of PVG.RT1a (RT1a) donor into PVG (RT1c) recipient. DA serum delayed significantly both the early and late rejection of PVG.RT1a heart grafts in PVG recipients. Removal of soluble class I MHC antigen from DA serum by affinity chromatography on a monoclonal anti-class I antibody column completely abolished the immunosuppressive effect. Continuous infusion of purified soluble class I antigen from DA rat liver, even from day 4 after heart grafting, induced a significant prolongation of graft survival. This effectiveness was donor-specific and amplified by the mixture of monoclonal anti class 1 (RT1a) antibody with DA serum--this being induced only by using continuous infusion but not by daily injection. The results indicate that soluble class I antigen can act as a specific immunosuppressive agent in allograft rejection and that its effect is amplified by monoclonal anti-class 1 antibody. PMID- 2219290 TI - Vascular thymus transplantation in rats. Technique, morphology, and function. AB - A new method of thymus transplantation is introduced, in which the graft is directly connected with the recipient's vascular system. This procedure was used both in euthymic rats and congenitally athymic nude rats. At all tested intervals after transplantation thymus grafts hardly differed from the recipient's own thymus in immunohistology and lymphocyte yield. In athymic nude rats, T cell dependent immunity, tested by mitogen- and alloantigen-induced T cell responses, as well as by antibody production and delayed-type hypersensitivity after ovalbumin administration, showed that vascular thymus grafts could generate T cell functions to euthymic control levels. We conclude that the technique of vascular thymus transplantation represents a valuable tool, either in fundamental research on thymus function, or for the purpose of immune (re)constitution. PMID- 2219292 TI - Expression and function of mutant Ia antigen in transgenic mice. AB - Cell surface expression of Ia antigens requires the assembly of alpha and beta heterodimers. We have produced a double transgenic mouse with a wild form Ak alpha gene and a mutant Ak beta (Ak beta MB) gene with d-allele substitution at positions 63 and 65-67. Initial studies indicated that the Ak alpha and Ak beta MB transgenes are not expressed on the surface of lymphoid cells of the transgenic mice. However, when spleen cells were stimulated with LPS prior to FACS analyses, Ak/Ak MB assembly and subsequent surface expression was induced. The tail skins from transgenic founder mice were rejected by the parental mice indicating a role for the mutant antigen on the allograft. In addition, the Ak transgenic mice on H-2q/q background can partially delete V beta 6+ T cells, suggesting the presence of the transgene product in the thymus. PMID- 2219293 TI - Resistant hepatic allograft rejection successfully treated with cyclophosphamide and plasmapheresis. PMID- 2219294 TI - Fine-needle aspiration biopsy of human liver allografts. Correlation with liver histology for the diagnosis of acute rejection. PMID- 2219295 TI - Erythropoietin therapy and the antibody levels of highly sensitized patients awaiting kidney transplantation. PMID- 2219296 TI - Fatal generalized acute graft-versus-host disease in a liver transplant recipient. PMID- 2219297 TI - Relevance of mesenteric lymph nodes to graft-versus-host disease following small bowel transplantation. PMID- 2219298 TI - Immunosuppressive action of low-dose heparin. Effect on skin allograft survival. PMID- 2219299 TI - Effect of a minimal number of donor rat islets on xenograft survival in mice. PMID- 2219300 TI - Posttransplant cecal volvulus. PMID- 2219301 TI - Bile cytology versus pancreatic juice cytology for diagnosis of allograft rejection. PMID- 2219302 TI - Our experience with bile cytology and pancreatic juice cytology. PMID- 2219303 TI - Antibody-induced rejection of long-term, functioning pig proislet xenografts in CD4+ T-cell-depleted diabetic mice. PMID- 2219304 TI - The effect of continuous anti-CD4 monoclonal antibody therapy on fetal pig pancreas xenografts in nonobese diabetic mice. PMID- 2219305 TI - An analysis of concordant xenograft rejection in the nude rat model. PMID- 2219306 TI - Enhancement of rabbit skin allograft survival by pretransplant and peroperative hepatic antigen treatments. PMID- 2219307 TI - Adhesion of lymphocytes to stimulated vascular endothelial cells occurs via ICAM1 dependent and ICAM1-independent pathways. PMID- 2219308 TI - The importance of the ICAM-1/LFA-1-dependent pathway in in vitro cytotoxicity against cultured human kidney cells. PMID- 2219309 TI - A model of the corneal allograft reaction. PMID- 2219310 TI - Prolongation of heterotopic human corneal graft survival in mice treated with an anti-CD4 monoclonal antibody. PMID- 2219311 TI - The effect on researchers of handling human fetal tissue. PMID- 2219312 TI - Prolongation of fetal pancreas allograft survival in mice treated with anti-IL-2 receptor monoclonal antibody (PC61) conjugated with idarubicin. PMID- 2219313 TI - Beneficial effects of monoclonal antibody targeting of CD4+ cells during the sensitisation but not effector phase of accelerated rejection of rat cardiac allografts. PMID- 2219314 TI - Castanospermine, an alpha glucosidase inhibitor, prolongs renal allograft survival in the rat. PMID- 2219315 TI - Urocanic acid in allotransplantation. PMID- 2219316 TI - The interaction of IL-2 and IL-4 with the effects of deoxyspergualin. PMID- 2219317 TI - The effect of 2-deoxyguanosine on graft immunogenicity. PMID- 2219318 TI - A prospective study of the effect of diltiazem in renal allograft recipients receiving cyclosporine A: preliminary results. PMID- 2219319 TI - Elimination of nonimmunological causes of cadaveric renal allograft loss--an attainable goal? PMID- 2219320 TI - Kidney preservation with UW solution: the nature of the impermeant. PMID- 2219322 TI - Heart/lung transplantation in Australia: early results of the St Vincent's program. PMID- 2219323 TI - Cells infiltrating heart allografts: specificity and function. PMID- 2219321 TI - Inhibition of PHA lymphocyte responses by cyclosporine and methylprednisolone. PMID- 2219324 TI - Determinants of successful liver transplantation. PMID- 2219325 TI - 31P-magnetic resonance spectroscopy in evaluating hepatic function: a possible application in donor assessment prior to liver transplantation. PMID- 2219326 TI - Complications of sclerotherapy for esophageal varices in liver transplant candidates. PMID- 2219327 TI - Glucose homeostasis in the rat after liver transplantation. PMID- 2219328 TI - Are kidney and pancreas rejection simultaneous events in combined transplants in dogs? PMID- 2219330 TI - Pretreatment of canine whole pancreas allografts with monoclonal antibodies does not prolong graft survival. PMID- 2219329 TI - 48-hour cold storage of the rat pancreas. PMID- 2219331 TI - The role of V beta 8 cells in disease recurrence in isografts in diabetic NOD mice. PMID- 2219332 TI - Bone marrow transplantation in children using closely matched related and unrelated donors. PMID- 2219333 TI - 99m-TC-DTPA aerosol lung clearance in the early detection of interstitial pneumonitis in pediatric bone marrow transplant patients. PMID- 2219334 TI - Sensitive detection of residual acute lymphoblastic leukemia cells for monitoring bone marrow purging. PMID- 2219335 TI - Comparison of magnetic particles for immunomagnetic bone marrow purging using an acute lymphoblastic leukaemia model. PMID- 2219336 TI - Organ donation in Singapore. PMID- 2219337 TI - Human hepatic preservation using Marshall's solution and University of Wisconsin solution in a controlled, prospective trial. PMID- 2219338 TI - Preliminary results of the European Multicenter Study on UW solution in liver transplantation. The Study Group. AB - The introduction of UW solution in clinical liver transplantation has had a tremendous impact on clinical practice. The preliminary evaluation of data in this interim report with UW solution in the European setting does confirm the clinical results as reported by the Belzer and Starzl groups. These data on the UW solution in its original composition concern in already 43% a population of liver transplant procedures performed with cold ischemia times of more than 12 hours without clinical evidence of detrimental effects due to preservation times up to 26 hours. A comprehensive analysis of the results of this study will be performed upon completion of the 1 and 3 month follow-up. In this analysis all preservation related characteristics will be presented and statistically evaluated. PMID- 2219339 TI - Clinical use of UW solution or a simplified liver preservation solution prior to transplantation in 179 human livers, December 1987-July 1989. PMID- 2219340 TI - The functional effects of a colloid in liver cold storage preservation. PMID- 2219341 TI - Coenzyme Q. alpha tocopherol graft uptake and lipid peroxidation in human liver transplantation: evidence of energy metabolism protection in University of Wisconsin (UW) solution-preserved livers. PMID- 2219342 TI - Lactobionate as the most important component in UW solution for liver preservation. PMID- 2219343 TI - A pure class II MHC disparity does not induce rejection of cornea or heart grafts in the rat. PMID- 2219344 TI - Prevention of early graft failure by the calcium channel blocker nisoldipine: involvement of Kupffer cells. PMID- 2219345 TI - Preservation of isolated rat and human hepatocytes in UW solution. PMID- 2219346 TI - Effect of flush-perfusion with Euro-Collins solution on pulmonary arterial function. PMID- 2219347 TI - First results of the multicenter study of HTK protection for kidney transplants. PMID- 2219348 TI - Preliminary results of the European Multicenter Trial of UW and Euro-Collins solutions in kidney transplantation. The Study Group. PMID- 2219349 TI - Specific effect of University of Wisconsin solution on renal hemodynamics and microvasculature in canine kidney preservation. PMID- 2219350 TI - Rescue perfusion of the cold-stored kidney. PMID- 2219351 TI - Beneficial effect of superoxide dismutase (SOD) on erythrocyte trapping and 6 keto-PGF1 alpha TxB2 ratio after ischemia-reperfusion in kidney transplantation. PMID- 2219352 TI - Prevention of acute renal failure after kidney transplantation by treatment with rh-SOD: interim analysis of a double-blind placebo-controlled trial. PMID- 2219353 TI - Heart-lung transplantation: graft function postoperatively. PMID- 2219354 TI - Comparison of Euro-Collins and UW-1 solutions for lung preservation using the parabiotic rat perfusion model. PMID- 2219355 TI - Effects of calcium channel blockage in postischemic lung reperfusion. PMID- 2219356 TI - Single flush perfusion with Euro-Collins solution in lung preservation: clinical assessment of early graft function. PMID- 2219357 TI - Free radical ablation prevents ischemic injury after long periods of cold storage in rat pancreas transplantation. PMID- 2219358 TI - A long-term study of Parkinson's patients subjected to autoimplants of perfused adrenal medulla into the caudate nucleus. CPH Neural Transplantation Group. PMID- 2219359 TI - Transplantation of allogeneic isolated hepatocytes induces a specific prolongation of allograft survival. PMID- 2219360 TI - Fetal liver cell transplantation: survival of grafted BALB/c lysosomal storage disease mice. PMID- 2219361 TI - Transplantation of bone marrow with vascularized bone. PMID- 2219362 TI - Effective radiation therapy for crescentic glomerulonephritis after renal transplantation. PMID- 2219363 TI - Problems of renal transplantation in Pakistan. PMID- 2219364 TI - Monotherapy with cyclosporine in kidney transplantation. PMID- 2219365 TI - Glomerular disease after kidney transplantation. PMID- 2219366 TI - Tubular markers in renal transplant patients under cyclosporine. PMID- 2219367 TI - Influence of cyclosporine on C-peptide levels in kidney allograft recipients. PMID- 2219368 TI - Cyclosporine: its time of impact on kidney graft survival. PMID- 2219369 TI - Quadruple drug induction treatment in patients with ATN-kidneys: expensive but effective. PMID- 2219371 TI - Differential crossmatch in renal transplantation: allopositive historical crossmatch (B and/or T) but current T-cell negative crossmatch. PMID- 2219370 TI - Monitoring of renal transplant patients with interleukin-2 and interleukin-2 receptor enzyme immunoassay and interleukin-2 receptor immunocytology. PMID- 2219372 TI - Nonrandomized comparative study between University of Wisconsin cold storage and Euro-Collins solution in kidney transplantation. PMID- 2219373 TI - Efficacy of a modified University of Wisconsin solution in rat liver preservation: its prevailing role on vascular endothelium rather than hepatocyte protection. PMID- 2219374 TI - Evaluation of a prospective protocol for liver transplantation in the treatment of acute liver failure. PMID- 2219375 TI - Gallbladder conduit vs end-to-end anastomosis of the common bile duct in orthotopic liver transplantation. PMID- 2219376 TI - Transplantation aspiration cytology in the diagnosis of steroid resistant rejection in liver allograft patients. PMID- 2219377 TI - Rapid therapeutic decision-making using frozen sections of human liver allograft biopsies. PMID- 2219378 TI - Pathological and immunohistochemical features of graft liver antibody-mediated rejection. PMID- 2219379 TI - Hyaluronic acid in the assessment of liver graft function. PMID- 2219381 TI - Recruitment of lymphocytes to human liver allografts during rejection. PMID- 2219380 TI - Systemic fibrinogenolysis in liver transplantation. PMID- 2219383 TI - Serum tumor necrosis factor alpha in patients following liver transplantation. PMID- 2219382 TI - Induction of ICAM-1 on hepatocyte membranes during liver allograft rejection and infection. PMID- 2219384 TI - HLA class I matching is responsible for the hepatic lesions in recurrent viral hepatitis B after liver transplantation. PMID- 2219385 TI - Influence of long-term cyclosporine therapy on chronic liver disease after renal transplantation. PMID- 2219386 TI - Reliability of cytoimmunological monitoring after heart transplantation by consensus measurement: a multicenter study. PMID- 2219387 TI - Cardiotoxicity of cyclosporine A: light and electron microscopic findings in pigs and dogs. PMID- 2219388 TI - New immunosuppressive agents in experimental allogeneic heart transplantation. PMID- 2219389 TI - Prolongation of rat cardiac allograft survival by pretreatment of the donor to reduce class II antigen expression and dendritic cell content. PMID- 2219390 TI - Diagnosis and treatment of graft rejection in experimental and clinical small bowel transplantation. PMID- 2219392 TI - The effect of ketanserin on the immediate posttransplant function of canine kidneys. PMID- 2219391 TI - Cyclosporine and the ischemic rat liver. PMID- 2219393 TI - Contribution of nonendocrine tissue to the immunogenicity of endocrine pancreatic transplants. PMID- 2219394 TI - Transplantation of MHC incompatible vascularized mesenteric lymph nodes: identical pattern of lethal graft-vs-host disease as induced by small bowel grafts. PMID- 2219395 TI - Xenogeneic liver transplantation: its influence on secondary allogeneic graft rejection. PMID- 2219396 TI - A single exposure to ultraviolet radiation in vivo suppresses allogeneic responses in rat mixed lymphocyte cultures. PMID- 2219397 TI - Induction of tolerance after facilitation of engraftment with a monoclonal antibody anti-MHC class II in MHC fully allogeneic transplantation. PMID- 2219398 TI - Inhibition of leucocyte chemotaxis by immunosuppressive drugs: an important mode of action? PMID- 2219399 TI - Extrarenal pathology of cyclosporine: a lasting challenge. PMID- 2219400 TI - Mechanism of rejection of MHC class I-disparate murine skin grafts--histological and immunohistochemical studies of the rejection phenomenon. PMID- 2219401 TI - Examination of sex differences in tolerance induction by donor-heated lymphocyte pretreatment in a rat cardiac allograft model. PMID- 2219402 TI - Long-term (25-year) survival after renal homotransplantation--the world experience. AB - A follow-up is provided for 64 patients treated with renal transplantation at the University of Colorado before 31 March 1964. The 25-year survival was 15/64 (23.4%) and 14 patients (22%) are still alive after 25 1/2 to 27 years. There are 9 other survivors in the world from this era, distributed in 4 American and 2 European centers. All of the 25-year survivors received their grafts from living related donors. PMID- 2219403 TI - Renal blood flow in the immediate posttransplant period as an index of the efficacy of organ procurement and preservation. PMID- 2219404 TI - Cyclosporin A-induced side effects in renal transplantation are related to the ratio of nonspecific/specific cyclosporin blood trough levels as analysed by radioimmunoassay. PMID- 2219406 TI - The use of the saphenous vein for arterial reconstruction in orthotopic liver transplant. PMID- 2219405 TI - Reactivity of peripheral blood lymphocytes to recombinant interleukin-2 in kidney transplant recipients. PMID- 2219407 TI - Graft-versus-host disease after orthotopic liver transplantation in a child. PMID- 2219408 TI - Prostaglandin E2 protects the isolated perfused rabbit liver from an oxygen free radical-induced injury. PMID- 2219409 TI - Cardiac transplantation in diabetic patients. PMID- 2219410 TI - Muscle flap closure for infected wounds after heart transplantation. PMID- 2219411 TI - Cyclosporin effect on ultrastructure of transplanted myocardium. PMID- 2219412 TI - Normal reproductive function in dogs with islet autografts. PMID- 2219413 TI - Prerequisites and initial experience for the noninvasive routine evaluation of viability of experimental and human organ transplants by magnetic resonance spectroscopy. PMID- 2219414 TI - The quality of life of donors, potential donors, and recipients of living-related donor renal transplantation. PMID- 2219415 TI - Barriers to organ donation among housestaff physicians. PMID- 2219416 TI - Rational drug use: an unsolved problem. PMID- 2219417 TI - Can education of the community help sleeping sickness control: a study from Cameroon. PMID- 2219418 TI - How to give priority to family planning in PHC programmes. PMID- 2219419 TI - Specialization and referral among the n'anga (traditional healers) of Zimbabwe. PMID- 2219421 TI - Experience with an active labour management protocol and reduction of caesarean section rate in Nicaragua. AB - Prospective data are presented on the outcome of labour in 67 women with uncomplicated pregnancy, who attended a rural Nicaraguan hospital and were managed actively in labour. No dystocia occurred and the caesarean section rate was 0%. Active management of labour is safe and feasible in a rural hospital setting. It results in a low caesarean section rate and reduced maternal mortality and morbidity, without compromising perinatal outcome. PMID- 2219420 TI - The village health worker project in Lesotho: an evaluation. PMID- 2219422 TI - Gastroscopy in a West African rural mission hospital. AB - The results of 1075 fibreoptic gastroscopies performed in the Northwest Province of Cameroon are presented. Three hundred and fifty-three examinations showed pyloroduodenal ulcer disease, 111 showed macroscopic gastritis, and 37 had gastric carcinoma. Sixteen other diagnosis were made, with a positive finding in 620 cases. The benefits of the 'high-technology' gastroscope in a low technology setting are discussed. Included are examinations of a series of 46 patients with haematemesis and/or melaena, and 43 who had previous gastric surgery. PMID- 2219423 TI - Pancreatic calcification in diabetes mellitus at Ilorin, Nigeria. AB - Plain abdominal radiograph showed pancreatic calcification in four cases (5.2%) in a total of 77 cases of diabetes mellitus. All patients with calcified pancreas were insulin-dependent male diabetics. No direct relationship was observed between duration of illness and presence of calcification in the pancreas. Low incidence of pancreatic calcification among diabetics in recent reports from Nigeria probably suggests a changing pattern of the disease in the tropics. PMID- 2219424 TI - Electrocardiographic changes after recovery from measles. AB - Children with measles seen at our hospital had an initial electrocardiogram (ECG) and a repeat after 3 months. The patients were aged 5 months to 8 years (mean 19 months). The ECG changes observed after clinical recovery included T-wave inversion in eight patients (16%), flattening in eight patients (16%), prolonged PR interval in six (12%), prolonged Q-Tc in three (6%) and low QRS amplitude in four (8%). At least one ECG change was present in 18 patients (36%) after recovery, 14 of these were due to persistence of the changes noted during measles. The implication of above findings and the need for a longer-term follow up study are discussed. PMID- 2219425 TI - Typhoid perforation: further experience with end-to-side ileotransverse colostomy. PMID- 2219426 TI - Stability of drugs in the tropics. A study in Sudan. PMID- 2219427 TI - Psychosocial counselling and HIV infection. PMID- 2219428 TI - Antibiotic sensitivity patterns of bacteria causing meningitis. PMID- 2219429 TI - Insulin needs of developing countries. PMID- 2219430 TI - International Network for the Rational Use of Drugs (INRUD) PMID- 2219431 TI - Study of site and nature of injury as prognostic factors in tetanus. PMID- 2219432 TI - Causes of infertility among 1000 patients in Ghana. PMID- 2219434 TI - A drug delivery system for small hospitals. PMID- 2219435 TI - Ileo ascending colon anastomosis after resection of terminal ileum and caecum for benign diseases. PMID- 2219433 TI - Risk factors of vesico-vaginal fistulae in Maiduguri, Nigeria: a case-control study. PMID- 2219436 TI - Penetrating injury of the thigh. PMID- 2219437 TI - Mammographic calcifications due to filarial disease. PMID- 2219438 TI - Prescribing. PMID- 2219439 TI - Infertility: an approach to management in a district hospital in Ghana. PMID- 2219441 TI - The VIIth biennial scientific meet of the Asian Pacific Association for the study of the liver 19th--21 February, 1190 Jakarta, Indonesia. PMID- 2219440 TI - Gastric mucormycosis. AB - A case of gastric mucormycosis proven on culture and histologic examination and successfully treated with resectional surgery and Amphotericin B is described. PMID- 2219442 TI - Liver transplantation in India. PMID- 2219443 TI - Pathophysiology and treatment of ascites in cirrhosis. AB - Ascites is the most frequent complication in patients with cirrhosis of the liver. In these patients, the onset of ascites indicates a profound impairment of hepatic and renal function and splanchnic and systemic hemodynamics and is therefore associated with a poor prognosis, the probability of survival at one and five years being of about 50 and 20 per cent, respectively. In patients with cirrhosis and ascites, parameters estimating splanchnic and systemic hemodynamics and renal function are better prognostic indicators than those currently used to evaluate liver function. PMID- 2219444 TI - Dissolution of pancreatic stones. AB - Chronic calcific pancreatitis (CCP) is the most clear-cut form of chronic pancreatitis. Till date, the common treatment of CCP has been directed toward discontinuation of alcohol consumption if the disease is associated closely with alcohol abuse, relief of pain, enzyme replacement, and the management of some complications like diabetes mellitus, cyst or abscess of the pancreas, malnutrition etc. In 1979, the research group for chronic pancreatitis in Japan proposed the therapeutic policy for this disease as illustrated in Fig. 1. A plausible new treatment is the dissolution of protein precipitates or calcified stones in pancreatic ducts by oral or intravenous administration of drugs. PMID- 2219445 TI - Endocrine diarrhoeas: current concepts. AB - Chronic diarrhoea occurs in several endocrine gland disorders, largely in gut neuro-endocrine tumours, due to the release of various agents into circulation, which affect gastrointestinal function (Table I). In the strict physiological sense, these agents may be hormones (such as gastrin), paracrine substance (somatostatin), neurotransmitters or neuro modulators (vasoactive intestinal polypeptide; VIP) or unknown agent(s) yet to be identified. For each of these syndromes or diseases (Table I), this review considers the characteristics of diarrhoea, its pathogenesis and the therapeutic aspects. The approach to the diagnosis of these syndromes, including localization of tumour tissue and the selection of appropriate anti-tumor treatment are also outlined. PMID- 2219447 TI - [The kinetic characteristics of the process of the contact stimulation of cell multiplication in a chick embryo cell culture]. AB - As was reported elsewhere (Gasparian, Grigorian, 1989a, 1989b), the stimulation of cell proliferation takes place in established culture of chick embryo cells after adding a suspension of living or inactivated homologous cells. In the present paper the kinetic parameters of this process, termed as the contact stimulation of cell proliferation, were studied. The dose- and time-dependence of cell response to the stimulus is described. It was shown that the addition of cells activates cell growth both in exponential and stationary cultures. DNA synthesis in resting cells is seen initiated only if their continuous interaction with the added cells is provided. The nature of signals involved in the process of contact stimulation is described. PMID- 2219446 TI - [The stimulation of the transition of resting NIH 3T3 cells to proliferation under exposure to lysosomal inhibitors]. AB - Lysosomal inhibitors (amino acid methyl esters) and the platelet-derived growth factor stimulate the resting NIH 3T3 cells to enter the S period. Incubation of cells in the medium containing lysosomal inhibitors enhances protein accumulation and seemingly does not disrupt lysosomes. These results indicate that proliferative homeostasis depends on the metabolic status of cells and that catabolic processes activated in resting cells negatively influence the prereplicative reactions. PMID- 2219448 TI - [The effect of oligomycin and cycloheximide on the ultrastructure of the segregation apparatus and on protein synthesis in the erythrocytes of the common frog]. AB - The incubation of frog erythrocytes in the Ringer solution with novocaine (4.6 x 10(-3) M) during 24 hours at 10 degrees C provoked vacuole formation (segregation zones). Changes of the novocaine solution for a fresh Ringer solution and the following 48 hour incubation was accompanied by a decrease in the number of vacuoles both electron-translucent and containing membranous material. Simultaneously, the number of vacuoles with amorphous material only and with amorphous and membranous substances was seen to increase. Under the action of cycloheximide (1.10(-2) M) or oligomycin (2.5 x 10(-6) M) on erythrocytes with preformed vacuoles for 48 hours the total number of vacuoles and their dimensions decreased, with numerous amorphous inclusions appearing. Vacuoles with amorphous and membranous material increased in size. Similar ultrastructural changes in the segregation zones under the influence of both the inhibitors were observed showing the appearance of thick threads and a decreased share of electron translucent vacuoles. A specific effect of cycloheximide, compared to that of oligomycin, involved the expansion of smooth endoplasmic reticulum cisternae. Under the influence of novocaine, 3H-leucin incorporation in proteins of frog erythrocytes was intensified. However, this incorporation was considerably inhibited by cycloheximide. Erythrocytes with segregation zones were more inhibitor susceptible than erythrocytes without vacuoles. The inhibitory effect was stronger early after their administration to the incubation medium, compared to the later periods. PMID- 2219449 TI - [The effect of cryopreservation on the cytogenetic characteristics of a cell subline of skin fibroblasts from the Indian muntjac]. AB - After thawing cells, previously cryopreserved in the presence of dimethyl sulfoxide (DMSO), a decrease in their viability and increase in unscheduled DNA synthesis was observed. In 7 days, these parameters restored to the control level. Cryopreservation without DMSO resulted in the decrease in both cell viability and replicative and unscheduled DNA synthesis. In 14 days, these characteristics were seen to return to the normal level. Cryopreservation of cells without DMSO and their preservation in liquid nitrogen induced the frequency of chromosomal aberrations, mostly chromosomal breaks. The frequency of chromosomal aberrations increased with the duration of cell preservation in liquid nitrogen. The normal level was achieved following 7 days after cell thawing. Cells treated with DMSO only (without cryopreservation) display an increased number of chromosomal and chromatid breaks and translocations. Nonrandom distribution of chromosomal aberrations was observed, with particular chromosomes being involved in the appearance of dicentrics and translocations. The data obtained indicate that cryoprotective activity of DMSO is probably associated with the cell repair systems. The detected antimutagenic and mutagenic activity of DMSO may presumably reflect various conditions for its interaction with cells (with or without cryopreservation), as well as it may be specific for the muntjac cell line used in the present work. PMID- 2219452 TI - [The relationship between the spontaneous frequency of chromosome aberrations and the change in their frequency following mammography]. AB - Changes in chromosomal aberration rates, analysed for women 35-60 years of age exposed to 0.5-2 cGy during the mammography, suggested a relationship between the initial rates of chromosomal aberrations and those caused by the procedure. The spontaneous level of cytogenetic changes is assumed to be indicative of the degree of body radiosensitivity. PMID- 2219450 TI - [The cytolytic function of mononuclear phagocytes. II. Factors that determine the binding and lysis of tumor cells by activated macrophages]. AB - The effects of various modifiers upon the interaction of LPS- and BCG-activated macrophages with cells of mastocytoma P815 have been investigated. The efficiency of binding and lysis of the tumor cells is to a great extent determined by activation of the effector-cells, expression of the trypsin-sensitive receptors on the surface of macrophages, and by the type of target-cells. Introduction into the analytical system (effector-target) of unlabeled tumor cells or membrane preparations obtained from them inhibits substantially both binding and lytic activity of cytotoxic macrophages. If nontransformed cells or their membranes are applied, no significant changes in the investigated processes can be detected. Trypsinization of tumor cells as well as of activated but not resident macrophages modifies considerably the interaction of effectors with targets. The quantity of tumor cells bound with macrophages does not depend on the fact, which of the partners is subject to trypsinization, but it is much less than that of target-cells bound in the control. The incubation of activated macrophages with actinomycin D results in a substantial suppression of their lytic activity, whereas treatment of tumor cells with this inhibitor of protein synthesis leads to a considerable decrease in stability of the targets against lytic activity of the factor activated by effectors. The obtained data reveal the ways of selective binding and effective lysis of transformed targets by activated macrophages. PMID- 2219453 TI - [A device for immobilizing small biological objects under light optical study]. AB - A device constructed on the base of a slide and a coverslip is proposed for immobilisation of small biological objects. The device permits performance of gradual and reversible squeezing of live micro-objects. Using the above device it is possible to watch one and the same living object, (for example, a ciliate) repeatedly within a prolonged period of time. PMID- 2219451 TI - [The effect of preparations of non-histone chromosomal proteins on the expression of hetero-organic membrane antigens of kidney origin in a primary rat hepatocyte culture]. AB - The expression of membrane hetero-organic antigens of kidney origin, associated with the rat hepatomas in primary culture of intact adult rat hepatocytes, was investigated by means of the indirect immunofluorescence method using a specific immune serum. These antigens were observed on the membrane of some hepatocytes after their contact with nonhistone chromosomal proteins (NHCP), which were obtained from the kidney of intact rats from cells of hepatoma 27 and Zajdela hepatoma, or from the carcinogenic liver after a single diethylnitrosamine injection. Negative results were obtained after the incubation of hepatocytes in the medium lacking some of NHCP, or in that with NHCP obtained from the liver of intact rats. PMID- 2219454 TI - Bovine borreliosis: comparison of simple methods for detection of the spirochaete in the blood. AB - Natural Borrelia infection occurring in a calf was followed up using stained blood and buffy coat smears and direct observation of blood and buffy coat in order to compare these spirochaete detection methods. Direct examination of the platelet-plasma interface of the microhaematocrit capillary tubes after centrifugation allowed detection of two parasitaemias that were not seen in Giemsa stained blood smears. An ascending Babesia bigemina infection seemed to suppress the Borrelia parasitaemia. Spirochaetes were detected in five out of 37 Boophilus decoloratus ticks recovered from the infected calf. The blood and the haemolymph stages of Borrelia were measured. After treatment with oxytetracycline the spirochaete could no longer be detected. PMID- 2219455 TI - Isolation of five species of Eimeria from chickens in Bangladesh. AB - Five species of Eimeria, namely E. acervulina, E. tenella, E. maxima, E. brunetti and E. necatrix were identified in chickens in Bangladesh on the basis of lesions seen at post-mortem examinations of naturally infected birds, and on the dimensions of oocysts and the lesions seen in chicks experimentally infected with single oocyst derived strains. The use of filter top, polycarbonate cages permitted the isolation of strains without sophisticated animal isolators and is appropriate for use in laboratories throughout the developing world. Responses to a questionnaire sent to all known intensive poultry farms suggested that coccidiosis is a major disease. For control, producers rely mostly on management procedures and the tactical use of sulphonamides; in-feed chemoprophylaxis is not widely used. These control measures are unsatisfactory and recent coccidiosis outbreaks were reported from seven of 16 farms. There was evidence of a seasonal incidence in clinical coccidiosis. PMID- 2219456 TI - Serological survey for leptospiral antibodies in goats in St Elizabeth Parish, Jamaica, 1985-1986. AB - A serological survey of goats in St Elizabeth Parish, Jamaica, comprising the breeding herd at the Agricultural Development Corporation (ADC) facility at Hounslow, five commercial herds and 21 family herds was carried out in 1985-1986. The Leptospira microscopic agglutination test indicated that one or more serovars in the Canicola serogroup were the most prevalent. Repeated samplings of goats at ADC, Hounslow demonstrated an increase in portlandvere and canicola seropositive animals following the onset of warmer weather and of icterohaemorrhagiae seropositive animals following the autumn rains and cooler weather. Apart from a cluster of family goats seropositive to pomona there was no geographical separation of reactors to the other serovars tested in the parish. PMID- 2219457 TI - Cattle poisoning and mortality associated with tortoise clostridial toxicity in the Beletu District of Ethiopia. PMID- 2219458 TI - Mineral deficiency in ruminants in subsaharan Africa: a review. PMID- 2219459 TI - Complement activation in pulmonary tuberculosis. AB - The alterations in serum/plasma levels of total haemolytic complement activity (CH50), complement components C3 and C3d, and circulating immune complexes (CICs) in patients with pulmonary tuberculosis were analysed in relation to the severity of disease and treatment status. The mean levels of CH50, C3, C3d and CICs were significantly higher in untreated than treated patients and in normal controls. In the untreated group, the level of each of these four parameters except C3d was significantly higher in patients with far advanced disease than in those with moderately advanced disease, whereas the difference between treated patients and normal controls was not statistically significant for any of the four parameters tested. There were statistically significant correlations between levels of CICs and both C3 and C3d in the untreated tuberculosis patients. However, the correlations for the same parameters were not significant when treated patients were considered. The CH50 levels in tuberculosis patients suggest a functional classical complement pathway, which is essential for immune complex solubilisation. High C3d level in untreated patients is indicative of increased complement activation, which in turn shows significant correlation with levels of CICs. It appears that the intact and elevated complement proteins and their proper activation by CICs prevents tuberculosis from becoming a typical immune complex disease. PMID- 2219461 TI - Adenosine deaminase (ADA) in peritoneal tuberculosis: diagnostic value in ascitic fluid and serum. AB - Simultaneous determination of ascitic fluid and serum adenosine deaminase (ADA) activity was evaluated as a diagnostic aid in peritoneal tuberculosis. The ascites was due to peritoneal tuberculosis (group 1), cirrhosis of the liver (group 2), cirrhosis of the liver with spontaneous bacterial peritonitis (group 3), peritoneal malignancy (group 4), Budd-Chiari Syndrome (group 5) and miscellaneous conditions (group 6). Serum from patients of pulmonary tuberculosis and healthy volunteers was analysed for enzyme activity. In patients with peritoneal tuberculosis the ascitic fluid and serum ADA activity was significantly higher than for the other groups (P less than 0.001). Levels above 36 u/l in ascitic fluid and above 54 u/l in the serum suggest tuberculosis. The ascitic fluid/serum ADA ratio was also higher in patients with peritoneal tuberculosis than with other causes of ascites (P less than 0.01). A ratio of more than 0.984 was suggestive of tuberculosis. PMID- 2219460 TI - A comparison of the relative sensitivity of two types of Heaf gun. AB - A total of 696 secondary school children were given a Heaf test in one forearm with a magnetic head Heaf gun and in the other forearm with a fixed head gun. One week later the results were read blind. In 333 (48%) children the fixed head gun gave a more strongly positive result than the magnetic head gun, while in only 27 (4%) children did the magnetic head gun gives a more strongly positive result. These findings are statistically highly significant (p less than 0.001). PMID- 2219462 TI - The diagnostic value of an enzyme-linked immune sorbent assay using adsorbed mycobacterial sonicates in children. AB - We have evaluated the serodiagnosis of tuberculosis in children using mycobacterial sonicates in an enzyme-linked immunosorbent assay (TB ELISA), a method reported to have been used with success in adults. Attempts were also made to ascertain if prior BCG immunisation would influence the outcome of the test. Using clinically diagnosed and notified cases of tuberculosis as well as subjects in whom the condition had been excluded as controls, it was found that the TB ELISA showed very low degrees of specificity and sensitivity and consequently was not suitable as a diagnostic tool in identifying children aged 5 years or less with tuberculosis. In groups of older children the TB ELISA appeared to be much more promising and gave results more in keeping with those found in adults. In very young infants who were free from tuberculosis we showed that there was a cross reactivity with BCG. Thus it appears that, at present, serodiagnosis of tuberculosis in children is not practical. PMID- 2219463 TI - Ofloxacin and imipenem in the treatment of Mycobacterium fortuitum and Mycobacterium chelonae lung infections. AB - Two patients with Mycobacterium fortuitum and one patient with Mycobacterium chelonae lung infections were treated with ofloxacin and imipenem respectively. Of the former two, one had underlying inactive pulmonary tuberculosis and bronchiectasis and the other had silicosis. The latter had severe underlying bronchiectasis also. The treatments were well tolerated and the patients responded well. PMID- 2219464 TI - The significance of glucose intolerance in pulmonary tuberculosis. AB - We performed a sequential follow-up of oral glucose tolerance tests on 54 Nigerian patients with active pulmonary tuberculosis in order to determine the significance of glucose intolerance in tuberculosis. Twenty-three patients (42.6%) were found to have abnormal results, including three (5.6%) with a diabetic pattern and 20 (37.0%) with impaired glucose tolerance; 15 (75%) of the latter group had normal results after 3 months treatment while one each of the former group was diabetic, intolerant of glucose and normal respectively. Two patients with normal results initially had impaired glucose tolerance at the second test. Three months after full anti-tuberculosis medication, only one of the eight patients with impaired glucose tolerance at the second oral glucose tolerance test remained intolerant of glucose. Only one patient was frankly diabetic. Our results suggest that glucose intolerance in pulmonary tuberculosis is secondary to infection and is reversible. PMID- 2219465 TI - Tuberculous pleurisy--a family outbreak. AB - Three female members of a family presented with tuberculous pleurisy over a 4 month period. All three responded to chemotherapy but identification of the source of infection proved difficult. PMID- 2219466 TI - Eczema vaccinatum and postvaccinal BCG adenitis--case report. PMID- 2219467 TI - Renal allograft tuberculosis. AB - We present a case of miliary tuberculosis presenting as fever of unknown origin in an immunosuppressed patient following renal transplantation. Biopsy of the renal transplant revealed acid-fast bacilli histopathologically. Eye examination revealed bilateral choroidal tubercles. Recipients of kidney transplants with fever of undetermined aetiology should be investigated for tuberculosis and fundoscopy performed. PMID- 2219468 TI - Any questions? How should a patient be managed who is being treated for sputum positive pulmonary tuberculosis and becomes jaundiced in the third week of chemotherapy? PMID- 2219469 TI - Immunotherapy with Mycobacterium vaccae as an adjunct to chemotherapy in the treatment of pulmonary tuberculosis. AB - 47 patients with adult-type pulmonary tuberculosis attending the Chest Diseases Hospital in Kuwait were given a single injection of 10(9) irradiation-killed M. vaccae after 1 month of a 9-month course of chemotherapy. The patients were followed-up for 3 more months in double blind comparison with 65 patients given an injection of saline (placebo). The immunotherapeutic injection produced a small local lesion in 44/47 patients, 18 of which ulcerated and produced small scars. Immunotherapy made no measurable difference to the bacteriological, biochemical, haematological, or radiological parameters measured. However it was associated with significantly improved weight gain, reduced size of skin test response to Tuberculin, increased lymphocyte proliferation to common mycobacterial antigens, and increased antibody levels to mycobacterial antigens. The changes in skin test and LTT responses were related and occurred in 29% of patients whose recognition of common mycobacterial antigens returned to normal. The remaining patients did not differ in these respects from those receiving placebo. The proportion of patients whose responses were improved was very similar to that achieved using the same immunotherapeutic agent in a group of treated multibacillary leprosy patients. PMID- 2219470 TI - [Lithium treatment and kidney function]. AB - Systematic cross-sectional and longitudinal examinations of the kidney function of patients in prophylactic lithium treatment have established that the therapy, even when given for many years, does not affect the glomerular filtration rate or lead to kidney failure. Lithium treatment may induce polyuria and lowered renal concentrating ability, but these side effects do not presage deterioration of the filtration rate, and they are not dangerous if dehydration is avoided. It is now possible to revise and simplify the guidelines for laboratory monitoring of maintenance treatment with lithium. PMID- 2219471 TI - [Forms of care and children's infections. 1. Occurrence and causal factors]. AB - On an average, preschool children have 6-8 acute infections annually. This corresponds to approximately 80 sick-days including mild colds. If days in which the general health is affected only are included, approximately 25 days per child per annum are concerned. The amount of sickness in children attending day care centres is between 2-7 times as great as that of children cared for in their own homes. In particular, an increased risk has been demonstrated for children attending day care centres to develop conditions such as secretory otitis media, pneumonia, gastroenteritis, hepatitis A and meningitis. A close dose-response connection can be demonstrated between ill health and the number of children with whom the child is cared for. The increased possibilities of exposure to infection in day institutions must, therefore, be assumed to be the central factor for the excess morbidity demonstrated. The significances of a series of modifying factors in the pathogenesis, including age, genetically determined immunity, psychosocial stress, atmospheric contamination, quality of atmosphere and low temperatures, are reviewed. Despite the term "colds", there is no evidence that upper respiratory infections have any connection with cooling. With the object of establishing rational measures against spread of infection, the occurrence and routes of infection of the relevant microorganisms are reviewed. About 80% of the infections must be presumed to be viral. In children attending day care centres, viruses have been demonstrated in 10% of the children without symptoms. Air-borne infection appears to be responsible for a very limited proportion of infections. The routes of infection are mainly by direct or indirect contact infection e.g. via tables and toys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2219472 TI - [Forms of care and children's infections. 2. Consequences and possibilities for intervention]. AB - t may be calculated that between one fourth and one third of all infectious illnesses in preschool children in Denmark can be attributed to care in day care centres. A series of socially stressing problems have been demonstrated for parents with work outside the home in connection with care of their sick children. There is no evidence that children with many recurrent infections early in the preschool age become more resistant to infection with increasing age. On the contrary there is evidence that recurring middle ear infections and respiratory infections in childhood may have chronic sequelae and may possibly predispose to allergic disease. From a community medical standpoint, there is no doubt that day care centres are of importance in the spread of infection e.g. influenza epidemics in the adult population. On this basis, indications are found to attempt to institute measures which can reduce sickness in day care centres. Apart from prohibition of smoking, it is not clear whether improved indoor atmospheric conditions will improve the resistance in children. More restrictive turning away of children with very slight symptoms of colds is probably of limited value, whereas more prolonged convalescence for the individual child would probably reduce the number of children with recurrent infections. This necessitates a considerable number of days of care at home for parents with sick children. Intensified microbiological hygiene should be the central measure in intervention. This necessitates improved microbiological training of the staffs of day care centres. Children should be out-of-doors to a greater extent and the space should be increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2219473 TI - [Study of the quality of measurement by the Sickness Impact Profile. Assessment of the reliability of a method to determine the functional level of psychiatric patients]. AB - The Sickness Impact Profile (SIP) is a questionnaire method of assessing the functional level within 12 fields which together provide a generalized measurement of the level of health in agreement with the definition of health by WHO. In the present investigation, the method was employed for the first time occasion for 58 suitable psychiatric patients and the result of Rasch's item analysis of the replies to the individual questions showed altogether scales of good measurement quality. A single question, however, appeared to be unsuitable. The item-analysis is a demanding measurement for the internal validity and homogeneity and it supplements foreign investigations of the criteria-related validity of SIP. PMID- 2219474 TI - [Evaluation of the level of function before and after treatment at a psychiatric day-hospital. Are you better, or are you well]. AB - A pilot project was carried out to assess the effect of group therapy. This demonstrates the employment of a method of measuring general health, the Sickness Impact Profile. Employment of this method before and after the period of therapy could demonstrate significant improvement in relevant functional fields and development towards normalization of health in the 12 categories which describe this. PMID- 2219475 TI - [Alcohol consumption and organic damage. Views and attitudes of Danish patients and their relatives]. AB - A total of 201 patients and their relatives in a hospital in Copenhagen participated in a structured interview investigation about their knowledge of the long-term effects of alcohol and their attitudes to restrictions. The majority approved of an upper limit for alcohol consumption within the recommended limits but a total of approximately 1/3 preferred a higher limit. Only 28% realised that there was a difference in how much alcohol women and men can tolerate. The majority, but far from all of the participants knew that alcohol could damage the liver and brain but few knew of damage to other organs. A total of 64% had a positive attitude to prohibition of alcohol consumption in places of employment in Denmark. It is suggested that information about alcohol should be concentrated in the form of simple clear messages. PMID- 2219476 TI - [Acute alcohol poisoning in children in the Randers area 1978-1988]. AB - The purpose is to examine retrospectively the circumstances, clinical course and sequelae in 37 children (32 boys, 5 girls) admitted with acute alcohol intoxication during the 11 years 1978-1988. It is concluded, that the number of admissions has increased. Two distinct populations are found: 0-3 and 8-15 years. Strong spirits were usually involved, excessive amounts ingested because of inexperience and not at home. Admission is within two hours from last ingestion and most often at week-ends. 24% had histories of chronic behaviour problems. 32% had minor injuries. The maximal alcohol concentration found was 2.9%. None of the patients were found to be hypoglycaemic or had long term sequelae. PMID- 2219477 TI - [Acute alcohol intoxication in children. Diagnosis, treatment and complications]. AB - The purpose of this review is to describe the diagnosis, emergency treatment and further observation and complications. Alcohol poisoning and complications are underdiagnosed problems. Intoxication in young children is accidental and due to lack of experience in older children. Strong spirits are usually involved. The speed of elimination is greater than in adults and presumably 3-8 mmol/l/h. Fatal cases with alcohol concentrations less than 3.0% have been reported. The lethal dose is presumably 3 g/kg. Symptoms are as in adults but appear at lower concentrations. Infants do not reach a stage of exitation. Children are more prone to develop complications such as hypothermia, acidosis, electrolyte disturbance and trauma. Hypoglycaemia develops in 24-50% of cases, more frequently in infants and after starvation. The treatment is aspiration, admission to hospital, close observation, determination of core temperature, alcohol concentration, blood glucose-concentration and determination of serum electrolytes. Blood glucose should be monitored. Treatment is conservative but severely intoxicated children may require dialysis. PMID- 2219478 TI - [Hospital employees' knowledge about HIV disease. A study from 2 provincial hospitals]. AB - The knowledge of and attitudes to HIV infection were investigated by means of questionnaires during the period 1.10.1988 to 30.4.1989 in two small Danish Hospitals. Two hundred and thirty two nurses, 147 nursing aids, 44 doctors, 25 laboratory workers and 22 midwives took part in the investigation. The overall response was 99% of the staff contacted. The questionnaires were anonymous and were completed immediately and without use of any sources of information. Poor knowledge was revealed concerning symptoms, sources of infection, precautions to avoid infection, high-risk groups and patients duty to provide information. In fact, none of the groups exceeded 66% correct answers on these subjects. A total of 70% of the whole group had been in contact with patients, whom they suspected to be HIV-positive. Every third individual had felt insecure regarding HIV at work. Incidents at work had caused 18 employees to be tested for HIV. Only about half had been instructed about HIV. A total of 73% expressed needs for further instruction about the disease. The investigation shows difference between the staff opinion of possible claims on the patients about tests and to the policy of the Danish Department of Health concerning voluntary testing. PMID- 2219479 TI - [Complications of thrombolytic treatment of acute myocardial infarction]. AB - In a retrospective study twenty-one Danish medical departments recorded the number of serious adverse events in patients who had acute myocardial infarction and according to local routine received thrombolytic therapy. Of 278 patients who were given streptokinase 1.5 million IU intravenously in 1 hour, 37 had falls in blood pressure less than 80 mm Hg; two had haemorrhage which required transfusion; one was temporarily disabled after paravenous infusion of streptokinase and one had a fatal intracerebral haemorrhage. Three patients developed stroke of unknown cause. The randomised prospective studies from recent years have shown similar complication rates. Nine patients who had thrombolytic therapy but were subsequently shown not to have acute ischaemic heart disease had no adverse events. PMID- 2219480 TI - [Carcinoma of the lip. Therapeutic results and cosmetic assessment]. AB - The results of treatment of 283 patients with histologically verified infiltrating squamous cell carcinoma of the lip are presented. The cosmetic results after interstitial implantation of cesium needles, surgery or external irradiation are assessed. In tumours with the maximal surface diameter between 1 and 2 cm, fewer visible scars were found after implantation (6.9%) than after surgical excision (23%). The recurrence rate after interstitial cesium implantation is 12% and after surgery 15%. PMID- 2219481 TI - [Routine roentgen examination of the skull]. PMID- 2219482 TI - [Medical research in Greenland]. PMID- 2219483 TI - [Confidence intervals instead of p-values]. AB - International scientific journals expect authors of articles to an increasing extent to calculate confidence intervals for their statistical findings. Confidence intervals are more informative than p-values in hypothesis testing as the confidence interval expresses how great the value of an investigated effect may be anticipated to be in the population. Examples of calculation of confidence intervals are presented on the basis of data frequently occurring in medical investigations. PMID- 2219484 TI - [Treatment of interpleural pain]. AB - Since then, a great deal of work on this topic has been published. The literature is reviewed and indications, contraindications, dosage, mechanism of action and side effects are discussed. PMID- 2219485 TI - [Rational hemotherapy. Indications, complications and practical performance]. AB - Employment of allogenic blood products involves the risk of a series of complications in the recipient: transfusion-transmitted disease, immune suppression, immunological transfusion reactions and coagulopathy. Hepatitis C is the most common transfusion-transmitted infection with a post-transfusion incidence of 2-4%. Transfusion-transmitted AIDS plays a quantitatively lesser role but the course of the condition is frequently fatal. The duration of the period during which a HIV-sero-negative individual is potentially infectious is uncertain. After blood transfusion, the immune apparatus is suppressed, probably on account of the leukocyte content of the blood transfusion. These disturbances in immune function increase the risk of infection and possibly the frequency of recurrence of cancer after operative treatment of a series of neoplastic diseases. Coagulopathy after blood transfusion may be related primarily to the number of transfusions and can be counteracted by administration of the relevant coagulation factors. Rational hemotherapy aims at minimizing these transfusion related complications by restricting the indications for blood transfusion, blood component therapy, peroperative normovolaemic haemodilution, preoperative deposition of autologous blood and/or peroperative collection of blood and re infusion. Employing rational hemotherapy, it becomes possible to reduce the need for transfusion by 20-90% and hence the morbidity and the mortality connected with blood transfusion. PMID- 2219486 TI - [Iatrogenic biliary tract injuries]. AB - From 1984 to 1986 The Medico-Legal Council was heard concerning four cases of iatrogenic lesions of the common bile duct during cholecystectomy. The Council's statements show that lesions of the common bile duct or the common hepatic duct during otherwise uncomplicated, elective cholecystectomy are considered surgical malpractice and not accidental mishaps. PMID- 2219487 TI - [Arteriosclerosis in Greenlanders]. AB - X-ray examination of the lumbar spine of 268 Greenlanders and a corresponding number of Danes were reviewed in order to diagnose arteriosclerotic lesions of the abdominal aorta. In 10.4% of the Greenlanders and 11.6% of the Danes major calcifications were found. The two groups did not differ in distribution of age and sex of patients with arteriosclerotic lesions. It is known that arteriosclerotic complications occur less frequently in Greenlanders than in Danes. The study seems to indicate that this cannot be explained by a rarer occurrence of generalized arteriosclerosis. PMID- 2219488 TI - [Radiographic examination of the lumbar spine in Greenlanders]. AB - X-ray examinations of the lumbar spine from a two-year period in 268 Greenlanders and an equivalent number of danes were reviewed in order to diagnose all radiological lesions. Twenty-five percent of the X-ray examinations of the Greenlanders and 28% of the Danes showed normal conditions. Eighteen percent of the Greenlanders and 3% of the Danes had evident sacroliitis. Four Greenlanders and one Dane had radiological ankylosing spondylitis. The high frequency of sacroiliitis can probably be explained by the genetic structure of the population and the pattern of infections. Spondylolisthesis was found in 24% of the Greenlanders, confirming previous findings. Degenerative lesions, fractures, developmental anomalies and Scheuermann's disease were equally frequent in the two populations, while scolioses were less frequent among the Greenlanders than among the Danes. PMID- 2219489 TI - [Radiographic examination of the stomach in Greenlanders]. AB - X-ray examinations of the stomach and duodenum from a two year period of 135 Greenlanders and an equivalent number of Danes were reviewed in order to diagnose all radiological lesions. The results are presented. In 37% of the Greenlanders and 51% of the Danes, x-rays showed normal findings. Peptic ulcerations were diagnosed for the first time in 2.4% of Greenlanders over the age of 15 years. The incidence of gastric ulcer was 1.5% and of duodenal ulcer 0.9%. The male/female ratio was 1.3 in Greenlanders. The esofagus and cardia region of the Greenlanders revealed many serious lesions, emphasizing the importance of further investigations in this area. The incidence of peptic ulcer disease and gastric ulcer is higher than the incidence in Denmark but approximately the same as in the Faroe Islands. The incidence of duodenal ulcer is found to be lower among Greenlanders than in the other two populations. PMID- 2219490 TI - [Double contrast arthrography as a screening method of suspected meniscal lesions]. AB - On reevaluation after one year of experience with double-contrast-arthrography (DCA) we found in 83 consecutive patients with suspected meniscal lesion a true positive diagnostic frequency of 0.84, a true negative diagnostic frequency of 0.75, a true positive nosografic frequency of 0.87 and a true negative nosografic frequency of 0.70. This gives an increased diagnostic accuracy compared to the initial evaluation of the arthrografies. No complications of the examination were registered. As DCA demands fewer resources than arthroscopy, this method is suggested as a screening procedure in patients with possible tears of the menisci. PMID- 2219491 TI - [Smoking habits among children aged 11-15 years in 1988. A study of smoking habits and their connection with social background factors, health, satisfaction and social networks]. AB - A total of 1,671 schoolchildren aged 11, 13 and 15 years answered an anonymous questionnaire in 1988 on their social backgrounds, social networks, health, life satisfaction and health behaviour. The proportions who had tried to smoke were 24%, 51%, and 66% in the three age groups; the proportions of smokers were 3%, 8%, and 29%, and the proportions of daily smokers were 0%, 2% and 6%. More girls than boys were smokers but there was almost no difference if place of residence, social class, or family type were considered. Almost the entire variation could be explained by best friends' smoking habits and by the number of smokers at home. Smoking was associated with poor health, fatigue, school tiredness, school performance below the average, frequent contacts with friends outside school and at night, difficulties in discussion with parents, ease in discussions with friends, and with having close friends. The proportion of smokers, among children has been steadily declining since the first Danish nationwide survey was carried out in 1959. PMID- 2219492 TI - [Basic research and aimed research]. PMID- 2219493 TI - [Insulin-like growth factors and growth hormone]. PMID- 2219494 TI - [Polymyalgia rheumatica]. PMID- 2219495 TI - [Standardized treatment]. PMID- 2219496 TI - [Copper toxicity in animal cell cultures]. PMID- 2219497 TI - [Diagnostic use of measurements of gastrointestinal hormones]. PMID- 2219498 TI - [Disaster planning in Danish hospitals]. AB - With the object of obtaining insight into establishing of disaster planning in Danish hospitals, an investigation was carried out in the departments responsible. The insight of the house officer on duty and his immediate description for disaster planning were employed as indications of the level of establishment of disaster planning. This investigation indicates a low level of establishment of disaster planning and reveals the need for further training and information on this subject. PMID- 2219499 TI - [First aid, prehospitalization treatment, performed by non-professionals]. AB - In the Casualty Department of the Central Hospital in Slagelse, all acute referrals during a period of 48 hours (illness or accidents) were registered with the object of assessing the extent to which lay persons employ first-aid. First aid had been employed in half of the cases investigated but was considered relevant in 82% of the cases. The circumstances associated with performance of first-aid are discussed and proposals are made for improvement. PMID- 2219500 TI - [Mandibular fractures. 1. Etiology and fracture pattern in 348 patients]. AB - We reviewed 348 consecutive patients with 536 mandibular fractures treated in the ENT department of Aalborg Hospital from 1982 to 1986 retrospectively. The most frequent causes of mandibular fractures were violence (37.3%) and traffic accidents (36.8%) in adults, and bicycle accidents in children. A total of 85 patients (24.4%) had associated injuries. The anatomic distribution revealed a high percentage (41.4%) of condylar fractures, while the rest of the fractures were distributed in accordance with similar studies. In 32 edentulous patients, body and condylar fractures were most frequent. PMID- 2219501 TI - [Mandibular fractures. 2. Treatment, complications and late sequelae]. AB - A total of 536 mandibular fractures were reviewed as regards treatment and complications. Among the 348 patients, 216 (62.1%) were hospitalized. Compared to other studies, many patients (31.2%), particularly with condylar fractures, were treated conservatively with soft diet only. Open reduction was used in 23.7% of the patients. Thirty five patients (10.1%) developed complications such as infection and/or delayed union. Postoperative infection was positively correlated to delayed union. Treatment-delay predisposed to primary, but not secondary infection. No correlation between fracture dislocation and development of complications was observed. A total of 209 patients came for follow-up after observation periods varying between one and six years. 48.8% had no symptoms. The most frequent late complications were occlusive change (22.2%) and sensory disturbances in the mental region. The mean ability to open the mouth was 48.5 mm. In one third of the patients with condylar fractures, the jaw deviated to the side of the involved condyle, but this finding did not interfere with function. Radiographically, shortening and, in many young patients, remodelling of the fractured condyle could be demonstrated. Teeth in the line of fracture should in general be preserved. PMID- 2219502 TI - [Primary assessment of X-ray images in a casualty department]. AB - During a period of three months, the primary diagnoses made by the duty officer in the casualty department on x-rays taken on patients with orthopaedic conditions were compared with the definitive diagnoses made after a conference with the radiological department. The consequences of possible erroneous diagnoses were also recorded. A total of 634 regions were examined in 555 patients. Incorrect diagnoses were made in 55 regions (8.5%). In 21 of these, alterations in the primary treatment were required. All of the treatments could be corrected by telephone (7) or an additional visit by the patient (14). X-rays of the cranium and the spine are known to be difficult to evaluate by inexperienced doctors. This was also found to be the case in the present investigation. PMID- 2219503 TI - [Physical exercise among school children. A nation-wide sociomedical study of 1,671 children 11-15 years of age]. AB - A total of 1,671 children aged 11, 13 and 15 years from a nationwide random sample of schools completed an anonymous questionnaire on their social backgrounds, social networks, health, life satisfaction, and health behaviour. The proportion practising outdoor activities at least three times a week was 57%; 37% did some physical exercise in their leisure time sufficient to make them breathless or sweat at least four times a week; 43% at least four hours a week. Two thirds were active members of a sports club. A minority of 8% did not carry out any physical exercise during their leisure time sufficient to make them breathless or sweat. Boys did more physical exercise than girls irrespective of the measurement of exercise. The most important motives for physical exercise were to improve health, to get in good shape, to have fun, and to make new friends. More than 90% of the children intended to do physical exercise at the age of 20. High intensity of physical activity was associated with high social class, strong social integration in the peer group, easy contact with parents and friends, physical exercise among parents and best friends, high degree of life satisfaction, and good health. PMID- 2219504 TI - [Sexual habits of women aged 20-39 years. A comparison of 3 population-based studies from Nykobing Falster, Copenhagen and Nuuk/Godthab]. AB - The sexual habits in women aged 20-39 years chosen at random were investigated. A total of 513 women from Copenhagen participated while there were 586 women from Nykobing Falster and 661 women from Nuuk (Godthab) in Greenland. The women from Copenhagen replied to a questionnaire investigation while women from the other two regions were interviewed personally. The age of commencement of sexual activity was considerably lower in Godthab in women of all age groups than in Copenhagen and Nykobing Falster e.g. the prevalence of women with age on commencement of sexual activity less than or equal to 16 years was 70-80% in Godthab while the corresponding figures for Copenhagen were 50-60% and for Nykobing Falster 30-58%. Comparison with previous investigations revealed that the average age at the first coitus showed a tendency to decrease in all three regions during the past 20-30 years. The difference in the age at the first coitus between a provincial town (Nykobing Falster) and a city (Copenhagen) was present only in the case of women in the oldest age group (35-39 years) and a geographical levelling appears to have occurred in the younger age groups (20-24 years) concerning the age at commencement of sexual activity. Women in Greenland had significantly more partners than women in the two South Danish regions. In Godthab, the prevalence of women with greater than or equal to 40 partners was thus 22.4% while the prevalences in Copenhagen and Nykobing Falster were 3.5% and 0.3%, respectively. The prevalences of women with 0-1 partners were 1.7%, 10.7% and 20.4%, respectively in Godthab, Copenhagen and Nykobing Falster. PMID- 2219505 TI - [Rectoscopy and Hemoccult II in irritable colon. A prospective study]. AB - It was investigated whether Hemoccult-II test (H-II) could reduce the number of colonic examinations in patients with the irritable bowel syndrome, with normal rigid proctoscopic findings. A negative H-II was obtained in 299 patients from general practice and a positive test in nine. Colonoscopy was done in 157 and double contrast barium enema in 142 after random allocation. The nine patients with positive H-II all had colonoscopy. Among the 299 with negative H-II, colonic adenomas were detected in ten and an early cancer in an adenoma in the sigmoid colon; overlooked rectal adenomas were found in three, rectal cancer in one, rectal carcinoid in another and a coecal cancer, which could be palpated, in a third patient. Two patients with colonic cancer and one with adenoma were detected among those with positive H-II. All patients were followed by clinical examination after one year. In conclusion, colonic examination should carry a low priority in patients with symptoms of irritable bowel, negative Hemoccult-II and normal rigid proctoscopic findings performed by an experienced examiner. The investigation confirmed the recommendation of total colonoscopy in patients with a positive H-II and added support for increasing number of endoscopy services in contrast to those of diagnostic radiology, which should be reduced. PMID- 2219506 TI - [Treatment of women with severe pre-eclampsia in an intensive care unit during a 3-year period]. AB - During the period 1.1.1986-31.12.1988, the number of patients with severe preeclampsia referred to the intensive care unit in Sonderborg Hospital increased. On the basis of a retrospective study of the hospital records, possible reasons and certain characteristics of this increase are pointed out. Failure of treatment of severe hypertension and oliguria were the most frequent reasons for referral. Respiratory complications predominated: four women had pulmonary oedema and eight required ventilatory support. Despite difficulties in assessing the haemodynamic status, these nineteen cases appear to illustrate the unpredictable variation in severe preeclampsia per se. Insufficient volume expansion may explain a few episodes of oliguria, but neither excessive volume expansion nor unacceptable delay in observation appear to offer plausible explanations for the increase observed. The authors conclude that the frequency of haemodynamic complications in this analysis illustrated the potentially disastrous effect of preeclampsia in itself. Early delivery should always be considered in patients with even minor symptoms of treatment failure, regardless of the age of gestation. Should haemodynamic complications occur despite this, referral to an intensive care unit should be considered. PMID- 2219507 TI - [Convulsions after flumazepil]. AB - Two cases of convulsions following intake of the benzodiazepine antagonist, flumazepil, are presented. The etiology is discussed and special precautions are recommended for the diagnostic employment of the preparation. PMID- 2219508 TI - [Education in disaster medicine]. PMID- 2219510 TI - [Inhaled steroids and growth inhibition]. PMID- 2219511 TI - [Do two thirds of all small children have fluid in their middle ear?]. PMID- 2219509 TI - [Alcohol tests, legal safety and equality]. PMID- 2219512 TI - [Preventive effects of bicycle helmets]. AB - The total number of persons injured following bicycle accidents in Denmark is estimated to be more than 50,000 annually. In half of the injured cyclists, lesions localized to the region of the head occur. Bicycle helmets provide considerable protection against brain injuries which constitute 13%. Several investigations from abroad and from Denmark have demonstrated that protection of the head can reduce the number of deaths and of acute brain injuries due to bicycle accidents. On the basis of the literature, it is concluded that bicycle helmets provide good protection of the head in connection with bicycle accidents. When a bicycle helmet is purchased, it is important to ensure that the helmet fits the head, that vision is not impeded and that the chinstrap secures the helmet correctly. Legislation is necessary to ensure that bicycle helmets sold in Denmark fulfill the minimum safety requirements. PMID- 2219513 TI - [Effects of antihypertensive agents on lipoproteins and thrombocyte function]. AB - This article is a review of the literature concerning the effects of antihypertensive agents on the lipid status and thrombocyte function. Many investigations have revealed that thiazide diuretics, non-selective beta-blockers and beta-1 selective beta-blockers have resulted in alteration of lipids in a potentially atherogenic direction. Only thiazide diruetics have caused increase in low density lipoprotein, which is causally connected with increased tendency to atheroschlerosis. In some investigations, alpha-1 blockers have had a favourable effect on lipids in an atherogenic direction. Other antihypertensive agents appear, by and large, to be lipid neutral even although isolated investigations have demonstrated displacement of lipids both in positive and negative directions. Non-selective beta-blockers appear to alter thrombocyte function towards a greater tendency to aggregation while beta-1 selective beta blockers are neutral. Ca-antagonists, angiotensin converting enzyme inhibitors and ketanserin have, theoretically, anti-aggregatory effects on the thrombocytes but only few ex vivo and in vivo experiments have confirmed this effect. Monitoring of lipids is recommended before and after antihypertensive treatment. Finally, the effect on thrombocyte function should be considered in the choice of hypertensive agent. PMID- 2219514 TI - [Serotonin and cardiovascular control]. AB - Serotonin is a monoamine and is widely distributed in the human organism. Serotonin is synthesized from the amino acid tryptophane and is broken down via mono-amino-oxydase enzymes to 5-hydroxy-indol-acetic acid and by acetylizing and methylizing to melantonin. In 1986, a consensus concerning the classification of the serotonergic receptors was established. Three main classes were determined, viz: 5-HT1, 5-HT2 and 5-HT3. 5-HT1 receptors were further subdivided into A, B, C and D-receptors and, of these, the 5-HT1A-receptor is involved in the centrally mediated blood pressure control via reduction in the pre- and postganglionic sympathetic activity. The 5-HT2 receptors are primarily involved in control of peripheral blood pressure where agonizing results in vascular contraction of the large arteries and veins and thrombocyte aggregation. The 5-HT1 receptors are also involved peripherally in connection with release of relaxing factors derived from endothelium. In vitro and in animal experiments, it has been demonstrated that serotonin is capable of inducing arrhythmia and myocardial dysfunction via 5 HT3 receptors. Several preparations with effects on both the central and peripheral serotonergic receptors are already marketed for treatment of hypertension and other conditions. PMID- 2219515 TI - [Scheuermann's disease]. AB - Scheuermann's disease is most frequently diagnosed in patients between 13 and 17 years and is subdivided into high, long and low kyphoses. The symptoms consist of pain which may be aggravated by physical exertion. Pain is most frequent and most severe in the long and low kyphoses. The etiology and pathogenesis are not entirely elucidated but it is probable that there is a genetic component, that the condition is not unifactorial and that it may be due to weakness in the epiphyseal plates of the vertebrae. Radiography reveals irregularities of the end plates of the vertebrae, frequently with Schmorl's impressions, narrowing of the intervertebral spaces, one or more wedge-shaped vertebral bodies and increased kyphosing. No effective symptomatic treatment is known but the patients should be advised about choice of career and work. In order to avoid hyperkyphosis and chronic pain, back and abdominal musculature must be strengthened and mobility in the spine improved. Gymnastics, swimming and cycling on stationary bicycles may be recommended but sports associated with jumping and marked stress for the spine must be warned against. In few and severe cases, treatment with a corset or operation may be necessary. PMID- 2219516 TI - [Diarrhea acquired abroad--traveller's diarrhea. Admissions to Medical Department C, Odense Hospital, during the period 1977-1988]. AB - A total of 106 out of 267 patients admitted with acute gastroenteritis to Medical Department C, Odense Hospital, during the period 1977-1988 had acquired the condition abroad. This group was investigated retrospectively. During the period of investigation, the number of patients with "traveller's diarrhoea" increased but compurized constantly approximately 40% of the patients admitted with acute gastroenteritis. The patients were investigated routinely for pathogenic intestinal bacteria and parasites and the etiology could be determined in 72%. Salmonella infections were found in 50% and 1/5 of these were caused by Salmonella typhi or Salmonella paratyphi. Double and triple infections occurred. 51% of the infections were acquired in Asia and Africa although less than 7% of Danish package tours visit these regions. Five patients (5%) developed serious complications. PMID- 2219517 TI - [Recurrent abdominal pain in schoolchildren 9-12 years of age]. AB - The frequency of recurrent abdominal pain (RAP) was investigated in a material of 664 Danish schoolchildren. 15% of the children aged 9-12 years had RAP, defined as at least three episodes of abdominal pain during a period of three months with pain of an intensity which affected the behavior of the child. In general, there was no significant difference in the frequency of RAP in boys and girls in the material, however, a preponderance of girls with RAP after the age of ten years was found. The investigation showed that symptoms such as headache, limb pains and diarrhoea were experienced more frequently among children with RAP. In general, RAP occurred more frequently among children in families with high frequencies of psychosomatic symptoms. 40% of all the children questioned lived in broken homes. A tendency to increased frequency of RAP was found among these children. Children who lived in a garden city had essentially lower frequencies of RAP than children from other areas. There was an evident preponderance of children with RAP in families who lived in flats. There was no significant difference in the school and occupational education of the parents and the frequency of RAP. PMID- 2219518 TI - [Treatment of medial femoral neck fractures in Denmark]. AB - Variations in the treatment of medial fractures of the neck of the femur were investigated by means of a questionnaire sent to all hospital departments which operated on these fractures. 91% replied. 86% of the departments used thromboembolic prophylaxis as a routine and 24% employed prophylactic antibiotics. Operation was only performed prophylactically on cases of impacted fractures in 24% of the departments. Orthopaedic departments operated earlier and more frequently preferred cancellous bone screws as the method of osteosynthesis rather than a sliding screw plate. The latter method was preferred by the non orthopaedic departments. Patients were mobilized earlier in the orthopaedic departments and fewer postoperative x-rays were taken than in the non-orthopaedic departments. PMID- 2219519 TI - [Percutaneous embolization of vascular abnormalities]. AB - In six male patients, percutaneous embolisation of symptom-producing vascular anomalies was performed with spirals or small particles. After a total of ten treatments, symptom-free states were obtained in half of the patients and definite improvement in the remainder. The results are so promising that this method of treatment will be continued. PMID- 2219520 TI - [10-22 years follow-up after truncal vagotomy and drainage of chronic duodenal ulcer]. AB - Long-term observation with a minimum 10 years on patients treated for duodenal ulcer is rare. This paper presents the long-term results of truncal vagotomy and drainage with a observation time of 16.8 years (range 10.1-22.4). A total of 146 patients were investigated. The side effects of the operation were moderate and only four per cent had unsatisfactory results at observation time. The recurrence rate was 25.5 per cent. Only 50 per cent of the recurrences were seen after the first eight years. A long follow-up time is therefore recommended in follow-up study of treatment of duodenal ulcer. PMID- 2219521 TI - [Leukemoid reaction caused by hypernephroma primary diagnosed as chronic granulocytic leukemia]. AB - A case of leukemoid reaction associated with renal carcinoma is presented. On account of the high leukocyte count and a palpable abdominal mass in the upper left quadrant, interpreted as an enlarged spleen, the primary tentative diagnosis was chronic granulocytic leukemia. Abdominal ultrasonographic scan revealed an enlarged left kidney and subsequent nephrectomy revealed a large hypernephroma. Leukemoid reactions associated with malignant disease are described in general with emphasis on the differential diagnosis. PMID- 2219522 TI - [Hyperhidrosis. Hypnotherapy of 2 patients with hyperhidrosis]. AB - Two cases of hypnotherapeutic treatment of psychogenic hyperhidrosis are presented. In both cases, organic aetiology could be excluded and conventional medical treatment modalities had no effect. In both cases, it was possible to modulate sweating in the trance state within less than a minute, thus supporting other reported cases of the effect of hypnotically induced modulation of autonomic responses. In the first case the psychological dynamics behind the physiological symptoms seemed unrelated to fundamental emotional and personal problems and relaxation and conditioning techniques in hypnosis had a positive effect in reducing the sweating to both objectively and subjectively socially acceptable standards. In the second case the hyperhidrosis was related to more fundamental personality problems and short term hypnotherapy proved ineffective in treating the condition. PMID- 2219523 TI - [Changes in risk factor levels in Osterbro]. PMID- 2219524 TI - [Analgesic-induced mortality]. PMID- 2219525 TI - [Surgical complications--surgical education]. PMID- 2219526 TI - [Hantaan virus infections]. PMID- 2219527 TI - [Lung transplantation]. AB - Isolated lung transplantation or combined heart and lung transplantation provides a new therapeutic possibility for patients with certain benign terminal pulmonary diseases. This method of treatment makes great demands on not only the donors but also the recipients. Following operation, which is undertaken in selected centres, life-long clinical control with immune suppressive treatment is essential. The method of treatment is associated with a series of complications and long-term survival does not appear to be optimal yet. A series of Danish patients have received lung transplantation abroad and are now followed in Danish special departments in cooperation with their own general practitioners. PMID- 2219528 TI - [High Dose Rate 192Ir-Microselectron]. AB - The HDR 192Ir-Microselectron is a new high-dose-rate remote afterloading apparatus using a small 192Ir source with very high activity, 370 GBq (10 Ci). The size of the source permits treatment through catheters with diameters as small as 1.9 mm. This makes it possible to give endobronchial treatment to lung cancer patients through a fibrebronchoscope in local anaesthesia. Preliminary results of treating cancer of the oesophagus, -prostate, -head and neck and breast cancers are promising. In addition the HDR 192Ir-Microselectron seems to have a promising potential in the treatment of several other tumours, especially in treating nonresectable intraabdominal tumours intraoperatively. PMID- 2219529 TI - [Social inequalities in child health status]. AB - The article describes the health situation in relation to demographic and social class variables in a sample of 1,671 schoolchildren aged 11, 13 and 15 years in Denmark. The proportions assessing their health as excellent, good, fair, or poor were 47%, 39%, 13%, and 1%, respectively. 22% reported daily symptoms and 74% weekly symptoms (20% one symptom a week, 54% two or more symptoms). During one week, 50% suffered from bad moods, 37% insomnia, 30% depression, 26% headaches, 22% nervousness, 19% back pain, 14% abdominal pain, and 12% vertigo. 37% had used medical drugs during the last month, most frequently for headaches (25%), colds (11%), coughs (9%) and abdominal pain (8%). Girls showed poorer self-assessed health than boys, more symptoms and more use of medication. The youngest pupils had the most frequent symptoms and the oldest least. There were no health differences when place of residence or family composition were considered, but there were clear social class differences. Pupils from the lowest social class and pupils whose parents were not included in the social class classification (e.g. disability pensioners) had the poorest self-assessed health, the most frequent symptoms and the highest use of medication. PMID- 2219530 TI - [Commitment of the mentally ill]. AB - This investigation consists of a cross-sectional study on 1 June 1989 of committed or compulsorily detained psychiatric patients in Denmark according to the legislation no. 118 of 13 April 1938. All of the departments which had received committed patients during the past five years participated. 87.2% replied. A total of 275 persons were found who were involuntarily admitted or compulsorily detained during their stay in hospital, or both. 59.9% of the patients were in closed departments and the remainder in open departments. The prevalence of committed or compulsorily detained patients was low compared with conditions in Norway and Sweden. Almost half of the patients were schizophrenic. The voluntarily admitted, but compulsorily detained patients comprised 28.8% of the reported patients. Notifications of compulsory detentions to the Ministry of Justice involved 34.4%. Half of the patients were admitted less than 2 1/2 months prior to the investigation but approximately 10% had been admitted for over ten years, which emphasizes the necessity of good physical and mental surroundings in psychiatric institutions. PMID- 2219531 TI - [Labor complications and interventions in immigrant and Danish women during the period 1983-1987]. AB - Based on data retrieved from the Danish Medical Birth Register, deliveries among Danish and immigrant women were compared in the years 1983-1987. The women were divided into two groups, primiparous and multiparous, and then compared by frequency and type of complications and interventions during labour. Five hospitals in the Copenhagen area were selected and more than 40,000 women were included in the survey. About 3,500 were from Yugoslavia, Turkey, Pakistan and Morocco and the remainder were from Denmark. An increased frequency of complications and interventions during labour was recorded among primiparous in comparison to multiparous during the period. This observation was not related to nationality. Stimulation of labour by intravenous drugs was more frequent among immigrant women than Danish women and was particular frequent among Moroccan and Pakistani women. Among these nationalities higher frequencies of complications were not recorded and the use of intravenous drugs did not imply more instrumental deliveries. It is presumed that one of the reasons why the use of intravenous drugs is more frequent among immigrant women is due to a feeling of insecurity during labour. This might be caused by defective communication between the woman in labour and the midwife. The subject calls for closer investigations based on case records and the women's own experiences. The necessities for special training of immigrant women and staff members in maternity wards are pointed out. PMID- 2219532 TI - [Acute iliofemoral venous thrombosis. 26 cases treated with thrombectomy, temporary arteriovenous fistula and anticoagulants]. AB - During a period of two years, 26 patients with acute iliofemoral venous thrombosis were treated with venous thrombectomy, establishing of a temporary arteriovenous fistula and anticoagulants as thrombolytic treatment was not possible. Twenty-five patients were followed-up after an average of 20 months with clinical examination, phlebography, venous strain-gauge pletysmography and vein-pump examination. At follow-up examination, 68% of the patients were free from symptoms, in 54% vein-pump function was normal and 79% had normal venous strain-gauge pletysmographic findings. One patient had venous claudication. Thrombectomy with temporary arteriovenous fistula formation offers a possibility of ensuring normal venous drainage from the lower limbs in patients with contraindications to thrombolysis. PMID- 2219535 TI - [Retrograde colo-colic invagination]. AB - A case of retrograde colo-colic intussusception, diagnosed preoperatively by straight films of the abdomen and confirmed by barium enema X-ray, is presented. The mechanisms behind intussusception are discussed briefly. PMID- 2219534 TI - [Upper abdominal pain and pre-eclampsia--HELLP syndrome]. AB - A 26 year old primiparous woman in the 30th gestational week presented with upper right abdominal pain. Clinical examination revealed direct tenderness under the right curverture, oedema, hypertension and proteinuria. Ultrasound scanning showed a normal gallbladder. Laboratory findings revealed Hemolysis, Elevated Liver enzymes and Low Platelet count. On account of suspected HELLP-syndrome cesarean section was performed. We suggest screening of all pregnant with upper abdominal symptoms suspected for preeclampsia by measuring platelet count and liver enzymes. PMID- 2219533 TI - [Giant cell arteritis. Can blindness be avoided?]. AB - It is recognized that temporal arteritis may cause blindness as one of the numerous symptoms. Three case histories are presented to illustrate this. In the discussion, the effect of rapid treatment with high-dose corticosteroids is emphasized to avoid blindness. PMID- 2219536 TI - [NovLet. A new pen-like device for insulin administration]. PMID- 2219537 TI - Electrochemical deposition of molecular adsorbates for in situ scanning probe microscopy. AB - We have studied gold and graphite electrodes in an electrochemistry cell under various solutions using the scanning tunneling microscope (STM). The gold (111) surface yields quite reproducible images and cyclic voltammograms. In situ voltammograms show that, under certain conditions, nanomolar quantities of DNA fragments can suppress the adsorption of a buffer salt of millimolar concentration. When the DNA concentration is reduced below that required for a monolayer coverage, the salt adsorption is restored. We show images of bare gold, gold covered with an adsorbate produced by the buffer salt, and gold prepared with a concentration of DNA fragments close to that required for monolayer coverage added to the buffer. Under these conditions, the surface is found to be uniformly covered with a characteristic structure. PMID- 2219538 TI - Scanning tunneling microscopy of planar biomembranes. AB - We combined planar membrane monolayer techniques with scanning tunneling microscopy (STM) to measure the thickness of metal-coated purple membrane (PM) isolated from Halobacterium halobium. Although the metal coating precluded obtaining high-resolution lateral information, it facilitated obtaining high resolution vertical information. For example, the apparent mean thickness of planar PM and variations in thickness of enzyme-treated PM could be detected and quantified at sub-nanometer resolution. PMID- 2219539 TI - [The density of cortical bone of the distal radius]. AB - The rigid fixation of distal radius fractures by T plates needs a bone substance of sufficient strength to insert screws. In case of advanced osteoporosis only the cortical cone will provide a secure fixation. In this investigation the results of measurement concerning the thickness of palmar and dorsal cortical bone of the distal radius are reported relating to age and sex. PMID- 2219540 TI - [Experimental determination of sliding friction during insertion of femoral intramedullary nails]. AB - No data have published concerning the procedure of driving in intramedullary nails. An extensive experimental device consisting of a contact-free distance measurement, a dynamograph connected to strain gages and an accelerometer now enabled this investigation. Among other things we determined the range of sliding friction for each stroke at different levels of nail-progression. Depending of the depth of nail-progression forces between 200 N und 400 N were measured. When the nail is stuck these values rise to over 1000 N. The sliding-process lasted between 10 ms and 20 ms. Knowledge of these data is of major importance for improvement of surgical technique and possible development of mechanical nail insertion aids. PMID- 2219541 TI - [The surgical treatment of thoracic wall instability]. AB - Cardinal symptom of the instability of thorax with paradoxical respiration is the irreversible respiratory insufficiency. The lethality is over 50%. For the treatment often besides the longterm respiration with the well known complications the operative stabilisation of the chest wall by osteosynthesis of the ribs by small plates. Thereby the mortality of this severe injury can be reduced significantly, if there is a good indication for osteosynthesis. PMID- 2219542 TI - [The treatment of post-traumatic recurrent anterior shoulder dislocation using Du Toit's operation]. AB - From 1.4. 1986 to 31.12. 1987 we operated 21 patients with a recurrent anterior dislocation of the shoulder with the Du Toit staple capsulorrhaphy. 20 patients we followed clinically and radiologically for an average period of one year and four months. By using a rating sheet 17 patients had an excellent and three patients a good result. There was, against other operation techniques, a minimally limiting of external rotation. We had no recurrents of dislocation. We concluded that the Du Toit staple capsulorrhaphy makes necessary only short postoperative immobilisation and renders an early return of motion and that a good function can be expected. PMID- 2219544 TI - [Meniscus replacement using Hoffa's infrapatellar fat bodies--initial clinical results]. AB - Between December 1986 and July 1988 a replacement of the absent medial meniscus was taken by means of the infrapatellar adipose body in seven patients. A replacement of the anterior cruciate ligament by means of the middle one third of the patellofemoral ligament was taken too. This operation was done for reconstruction of the synergism between the anterior cruciate ligament and the posterior horn of the medial meniscus. All patients are controlled in our special knee outpatient service. There were no complication postoperatively and on all seven patients a control arthroscopy was performed twelve months postoperatively. The subjective results are very satisfying because of the restoration of knee stability. The arthroscopic controls of the meniscal replacements, however, showed a reduction in size of the transplants after one year, the tissue was weak and not identical to that of a normal meniscus. Autologous strong tissue, e.g. quadriceps tendon, may have better presuppositions for meniscal replacement. PMID- 2219543 TI - [Treatment and results following rupture of the quadriceps tendon]. AB - Ruptures of the quadriceps tendon are rather uncommon and are usually due to minor trauma. From 1971 to 1986 we observed 13 spontaneous ruptures in contrast to a single case due to adequate trauma. The average age of the patients was 64.0 years. There is no alternative to surgical reconstruction of the ruptured or torn out quadriceps tendon. Tendon-repair with supportive wire-looping produces a good functional result. After immobilisation of the knee for five to six weeks intensive physiotherapy is required. The outcome of patients treated in this manner shows persisting slightly muscular atrophy of minor degree and limited knee-mobility with only a little all-day handicap. PMID- 2219545 TI - [Management of anteromedial instability of the knee joint]. AB - The management of patients with antero-medial rotatory instability of the knee is described. The therapy of the special patient depends on the age of the patient and the extent of instability. The therapy is also influenced by the degree of degenerative arthritis and differs between well trained and untrained persons. PMID- 2219546 TI - [Splenic rupture following arthroscopy]. AB - Retroperitoneal bleeding from splenic rupture occurred after initially uneventful arthroscopy. The diagnosis was finally set up in CT-scan, whilst peritoneal lavage was negative. Since there was no incidence of previous abdominal trauma and no abnormal findings in histology, spontaneous perioperative splenic rupture has been discussed. PMID- 2219548 TI - Interaction of ethanol and the high pressure nervous syndrome in rats. AB - The aim of this study was to determine whether administration of ethanol protects rats against the preconvulsive symptoms of high pressure nervous syndrome (HPNS). Male Sprague-Dawley rats were given either saline or 0.5, 1.5 or 2.5 g/kg ethanol i.p. After injection, the animals were individually exposed to helium-oxygen at 60 atmospheres absolute (atm abs) pressure. The chamber temperature was adjusted to counteract ethanol- and helium-induced hypothermia. Several behavioral parameters were scored continuously during the first 64 min after injection. The time spent in tremor at high pressure was significantly less in the 1.5 and 2.5 g/kg ethanol-treated groups. The number of jerks was significantly lower in the 2.5 g/kg ethanol-treated group. The two highest doses of ethanol induced a characteristic pattern of unsteady locomotion, which was returned to normal in the 1.5 g/kg group at 60 atm abs. Other behavioral effects of ethanol, such as depression of total motor activity, were also reduced. These results indicate that ethanol can significantly ameliorate some of the adverse symptoms of HPNS in freely moving rats. PMID- 2219547 TI - [The diagnosis of so-called whiplash injury of the cervical vertebrae. A case report]. AB - The acceleration injury of the cervical spine (so-called whip-lash injury) is a common traumatic mechanism in traffic accident. Severe damages are possible. Scepticism is necessary, if several hours or days are symptom-free. Radiological results which seem to prove an injury should be controlled. Severe injuries are in consideration of the symptom-free course incredible. This is demonstrated with a description of a case. PMID- 2219549 TI - Cardiovascular changes in anesthetized rats during exposure to 30 bar. AB - The effect of exposure to 30 bar (PHe = 29.0 bar, PN2 = 0.8 bar, PO2 = 0.2 bar) on left ventricular pressure, cardiac contractility, heart rate (HR), and arterial pressure was studied in anesthetized rats. During compression there was a progressive increase in maximal left ventricular pressure (LVPmax), maximal velocity of LVP rise (+ dP/dtmax) and fall (- dP/dtmax), systolic pressure (APsys), and pulse pressure (delta AP). The greatest increase in contractility per bar was found between 1 and 5 bar. Immediately after 30 bar was reached, LVPmax (19%), + dP/dtmax (60%), and - dP/dtmax (22%). APsys (19%), and delta AP (43%) were significantly increased from predive values, with an additional increase detected for all these variables after 60 min at 30 bar. An increase in estimated oxygen consumption (work load) of the heart was also found during compression to and at 30 bar. No changes in HR, mean arterial pressure, and end diastolic pressure were observed during the high-pressure exposure, indicating that the inotropic changes were not due to changes in peripheral hemodynamics. PMID- 2219550 TI - Effects of breathing-gas pressure on pulmonary function and work capacity during immersion. AB - Upright immersion induces respiratory mechanical changes that may impair pulmonary function during hyperbaric exercise. To evaluate this, 10 divers performed an incremental cycling protocol while immersed upright at 1.02 and 6.05 atmospheres absolute (atm abs). Air was supplied at each of two hydrostatic pressures: mouth pressure (Pm: to stimulate a mouth-held demand regulator) and lung centroid pressure (PLC). Subjects perceived air delivery at PLC to be more comfortable at each level of exercise at both absolute pressures (P less than 0.05). At 6.05 atm abs subjects perceived narcosis to be greater for Pm than for PLC air delivery. Hypoventilation was encountered at 6.05 atm abs with PLC air delivery and was further exacerbated when air was delivered at Pm (P less than 0.05). It was concluded that hypoventilation and narcosis are reduced whereas respiratory comfort is increased when air is delivered at PLC. This change is possibly due to improved pulmonary mechanics accompanying PLC air supply pressure. PMID- 2219551 TI - Combined arterial gas embolism and decompression sickness following no-stop dives. AB - Decompression sickness (DCS) has been clinically classified as Type I (predominantly joint pain) or Type II (predominantly spinal cord lesions). We present 3 cases that are all characterized by severe (Type II) DCS with signs and symptoms of spinal cord injury occurring in conjunction with arterial gas embolism (AGE). We consider the AGE "minor" because only 2 of the 3 subjects initially lost consciousness, and in all cases the signs and symptoms of the AGE had essentially resolved within 1 h or by the time recompression therapy began. DCS was resistant to recompression therapy, even though treatment began promptly after the accident in 2 of the 3 cases. None of the cases had a good neurologic outcome and there has been one death. None of the divers exceeded the U.S. Navy "no-stop" limits for the depths at which they were diving. We have observed a previously unreported clinical syndrome characterized by severe Type II DCS subsequent to AGE following pressure-time exposures that would normally not be expected to produce DCS. We postulate that AGE may have precipitated or predisposed to this form of DCS. PMID- 2219552 TI - Atmosphere contamination following repainting of a human hyperbaric chamber complex. AB - The Naval Medical Research Institute currently conducts hyperbaric research in a Man-Rated Chamber Complex (MRCC) originally installed in 1977. Significant engineering alterations to the MRCC and rusting of some of its interior sections necessitated repainting, which was completed in 1988. Great care was taken in selecting an appropriate paint (polyamide epoxy) and in ensuring correct application and curing procedures. Only very low levels of hydrocarbons were found in the MRCC atmosphere before initial pressurization after painting and curing. After pressurization, however, significant chemical contamination was found. The primary contaminants were aromatic hydrocarbons: xylenes (which were a major component of both the primer and topcoat paint) and ethyl benzene. The role that pressure played in stimulating off-gassing from the paint is not clear; the off-gassing rate was observed to be similar over a large range in chamber pressures from 1.6 to 31.0 atm abs. Scrubbing the chamber atmosphere with the chemical absorbent Purafil was effective in removing the contaminants. Contamination has been observed to slowly decline with chamber use and is expected to continue to improve with time. However, this contamination experience emphasizes the need for a high precision gas analysis program at any diving facility to ensure the safety of the breathing gas and chamber atmosphere. PMID- 2219553 TI - Measurement of static and dynamic pulmonary work during pressure breathing. AB - Various environments alter static and flow-resistive pulmonary mechanics. Of interest to diving physiologists is the negative pressure breathing induced during upright immersions without appropriate modification of air supply pressure. This paper outlines methodologic considerations for determining static and flow-resistive pulmonary work under such exposures. Ten males performed inspiratory pressure-volume relaxation maneuvers and spontaneous breathing in air, and during upright immersion with mouth pressure air supply. The immersed lung centroid pressure (PLC) was +1.19 kPa relative to the hydrostatic pressure at the sternal notch. Immersion elevated inspiratory static work from 0.36 to 1.74 J.liter-1 (P less than 0.05). Pulmonary flow-resistive work was elevated from 0.20 to 0.75 J.liter-1 (P less than 0.05), whereas pulmonary resistance, determined at 0.5 liter.sec-1, increased from 0.18 to 0.44 kPa.liter-1.sec (P less than 0.05). No significant changes in the iso-volume compliance of the lung tissue, chest wall, or total respiratory system were observed (P greater than 0.05). Results indicate that increases in the work of breathing are due to a combination of hydrostatic pressure imbalance, increased pulmonary resistance, and reduced end-expiratory total respiratory compliance. PMID- 2219554 TI - [Improvement of prostheses and orthotic aids for the handicapped using electric stimulation and the registration of bioelectric signals]. AB - Electro-mechanical devices can help a variety of patients with motor disabilities. Surface EMG from remaining muscles in an amputated arm can be used to control powered electronic hands, wrists and elbows. Sensory signals such as knee angle and ankle torque can be used to control the visco-elastic properties of a knee joint for above-knee amputees. Finally, percutaneous electrodes can be used to stimulate paralyzed muscles to replace hand function in quadriplegics and leg function in paraplegics. This article summarizes recent progress in each of these areas. PMID- 2219556 TI - [Allergy: update. What is new in the treatment of hay fever?]. PMID- 2219555 TI - [Interobserver agreement in the diagnosis and management of foot warts]. AB - The interobserver agreement in diagnosing the presence or the disappearance of plantar wart was assessed among ten Family Physicians from the Family Medicine Unit (FMU) of the Centre hospitalier de l'Universite Laval (CHUL). Physicians were trained to recognize predetermined clinical criteria for the presence (microthrombi, interruption of skin folds and hyperkeratosis) and disappearance (return of skin folds) of plantar warts. Sixty (60) untreated plantar lesions in 43 patients were examined independently by two to five available physicians. Twenty-two (22) patients who came for one to six follow-up visits generated 77 post treatment assessments of plantar warts. The observed agreement was 82% for diagnosis (49/60) and for cure (63/77). The agreement corrected for chance as measured by the Kappa coefficient was 0.60 for diagnosis and 0.61 for cure. A good degree of agreement on diagnosis and disappearance of plantar wart was achieved among the FMU physicians. PMID- 2219557 TI - [Cholesterol. The complex relation of an indispensable enemy. Interview by Robert Henry]. PMID- 2219558 TI - [Cholesterolemia, hypertension, diabetes: complex pharmacotherapeutic levels]. PMID- 2219559 TI - [Women and cardiovascular disease. Interview by Robert Henry]. PMID- 2219560 TI - Metabolism in vitro of cartilage proteoglycans in rat (pre)chondrocytes from different embryonic regions. AB - Diabetes in the mother may cause disturbances in the chondrocyte development in the embryo. A rat model was used to investigate whether this was reflected in the production of proteoglycans by cells from two embryonic regions. One of these regions is resistant (limb bud) and the other susceptible (mandibular arch) to malformation in diabetic pregnancy. Chondroitin sulphate proteoglycans from cultures of day-12 rat embryo limb bud and mandibular arch chondrocytes were extracted with guanidine-HCl and analyzed by gel chromatography after in vitro 35S-sulphate-labeling. Two sizes of proteoglycans (Kav 0.26 and 0.66 on CL-2B Sepharose) were found in both types of chondrocytes and in all media. The polysaccharide chain length was the same (Kav 0.36 on CL-6B Sepharose) for both proteoglycans. Elevated levels of D-glucose or beta-hydroxybutyric acid had no effect on either proteoglycan size or proportion, nor on polysaccharide chain length. However, there were differences (in all culture conditions) between limb bud and mandibular arch cultures in that the larger proteoglycan accounted for 80% of total radioactivity in the limb bud cultures, 53% in the mandibular arch cultures, and only 25-29% in the media from both types of cultures. Furthermore, different ratios between radioactive proteoglycans in medium and matrix suggested markedly different efficiencies for matrix formation in the two cell types. These findings indicate differences in the metabolism of the proteoglycans in these two cell types which may be related to the induction of mandibular malformation in diabetic pregnancy. PMID- 2219561 TI - Association between exposure to asbestos and pleural effusion. Results from a questionnaire study of 31,000 persons. AB - All visitors to a general health survey in 1979, 17,140 men and 14,371 women, completed a questionnaire on smoking habits, exposure to asbestos, silica and welding fumes, and diseases such as pleural effusion, pneumonia, cough, asthma and diabetes. Seven per cent of the men reported exposure to asbestos, 10% to welding fumes, and 6% to silica. Among those who reported work related dust exposure there was a higher proportion of smokers, and smokers exposed to dust smoked more tobacco per day than non exposed smokers. In the group of men 30-59 years of age, who did not indicate exposure to occupational pollutants 2.7% reported previous pleural effusions. However, among asbestos exposed men of the same ages, the prevalence was more than doubled (5.7%, p less than 0.01). This finding was highly significant in a logistic regression model where age and smoking habits were included. The data indicate that 10% or more of diagnosed cases of pleurisy could be associated with previous asbestos exposure. PMID- 2219562 TI - The influence of body temperature on traumatic vasospasm. AB - The effect of hypothermia on traumatically induced vasospasm was studied in an in vivo model of the rabbit ear artery. Spasm was induced by standardized compression of a 3.2 mm segment of the artery for 3 s. The internal diameter was continuously measured with the aid of an operating microscope during transillumination of the artery. Measurements were begun before spasm induction and continued until the spasm was completely resolved. Spasm was first induced at normothermia and then after reduction of the body temperature by 1.0 degrees C and 1.75 degrees C. The spasm was evaluated in terms of its duration, intensity (% reduction of initial diameter) and severity (area under the curve where diameter was plotted against time). The results were compared with those in a control group which was kept normothermic. Reduction of the body temperature caused a significant increase in the duration of the spasm and increased its severity, but did not influence its intensity. PMID- 2219563 TI - EMLA for pain relief during arterial cannulation. A double-blind, placebo controlled study of a lidocaine-prilocaine cream. AB - The aim of the study was to evaluate the effect of a lidocaine-prilocaine cream (EMLA cream, Astra) in relieving pain during arterial cannulation. The study had a random, double-blind, placebo-controlled design and included altogether 90 patients. All the patients were premedicated with an opioid before cannulation. An EMLA application time of 60 minutes was used in 60 patients (30 EMLA/30 placebo) and there was no difference in the pain reaction measured on a visual analogue scale (VAS) or on an observer's verbal scale. The study was extended with a further 30 patients (15 EMLA/15 placebo) with an application time exceeding 90 minutes. Between these groups pain experience measured by VAS did not show any significant difference although the mean value was lower in the EMLA group. Observer ratings showed a significant (p less than 0.01) difference in distribution towards lower ratings in the EMLA group. In conclusion EMLA was found to have a weak, but measurable effect when the application time exceeded 90 minutes but not after 60 minutes. PMID- 2219564 TI - Immune status and immune therapy of renal cell carcinoma. AB - At present, no sufficient therapy for metastatic renal cell carcinoma is available. Several immunotherapeutical protocols have been studied, success rates, however, were inconsistent. The purpose of this study was to assess the pretherapeutic immunological status of 13 patients with metastatic and 16 patients with nonmetastatic renal cell carcinoma and of 15 healthy volunteers. Determined were differential blood counts, lymphocyte subpopulations, beta 2 microglobulin, tumor necrosis factor (TNF), neopterin, immunoglobulin, fibronectin and ferritin. Additionally, these parameters were recorded for monitoring an immunotherapeutical approach with the xenogeneic biological response modifier Keyhole limpet hemocyanine (KLH) in 10 patients with metastatic and in 5 patients with nonmetastatic disease. The pretherapeutic immunological status of patients with metastatic disease was characterized by significantly reduced T4-, T8- and B-cell counts. Significantly increased were granulocyte counts, beta 2-microglobulin, neopterin and TNF. In patients who did not suffer from metastases, only beta 2-microglobulin and neopterin were increased significantly. During immunotherapy, in patients with metastases, there was a decline of lymphocyte subsets and of the T4/T8-ratio, which correlated with progress of the disease. Humoral immune parameters showed no changes compared to pretherapeutic values. In patients who did not suffer from metastases, cellular immune parameters showed stable values during immunotherapy; neopterin, beta 2 microglobulin and TNF increased considerably. These findings indicate immunosuppression in patients with metastatic renal cell carcinoma, increasing with progression of the disease and possibly impairing the immunostimulating effects of biological response modifiers during immunotherapy. In conclusion, the clinical response of metastatic renal cell carcinoma to immunotherapy might be improved if the immunostimulant is combined with agents suitable to overcome immunosuppression, i.e. low doses of cyclophosphamide or inhibitors of prostaglandin synthesis. In addition, assessment of immune parameters for monitoring the actual immune status of a patient and the immunological effects of therapy was found to be a necessary part of immunotherapy. PMID- 2219565 TI - Effects of nifedipine on renal cortical and medullary blood flow in two-kidney, one-clip renovascular hypertension in rabbits. AB - The effects of nifedipine, a calcium antagonist, on blood pressure and renal regional blood flow were investigated in two-kidney, one-clip renovascular hypertensive rabbits. At 1 week after left renal artery constriction, in the constricted group, systemic blood pressure (BP) significantly rose with the elevation of plasma renin activity (PRA). In both kidneys, renal vascular resistance (RVR on the constricted group was significantly increased as compared to that in the control group. In the clipped kidney, total renal blood flow (RBF) and renal cortical blood flow (RCBF) of the constricted group were significantly decreased, while renal medullary blood flow (RMBF) remained at the control value. In the nonclipped kidney, RBF and RCBF of the constricted group did not significantly change, and RMBF was significantly increased as compared to that of the control group. After administration of nifedipine for 1 week (1.0 mg/kg/day), BP in the constricted group was decreased to the control level and PRA in both groups was increased. The percent change of BP in the constricted group was significantly decreased and the percent change of PRA in the constricted group was significantly increased as compared to those in the control group. Nifedipine increased RBF, RCBF and RMBF and decreased RVR of both kidneys in each group. In the nonclipped kidney, the percent change of RBF, RCBF and RMBF of the constricted group was significantly increased and the percent change of RVR was significantly decreased as compared to those of the control group. In the clipped kidney, only the percent change of RBF of the constricted group was significantly lower than that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2219566 TI - Cancer incidence in patients on chronic dialysis and in renal transplant recipients. AB - A markedly increased incidence of cancer in renal transplant recipients is now recognized; to determine if immunosuppression alone may be responsible for this increase in risk, cancer incidence was compared in 709 renal transplant recipients and 317 dialysis patients. Malignancy developed in 19 transplant recipients (2.7%) and in 33 patients on chronic dialysis (10.4%). In our report an excess of skin cancer was observed in the transplant series while tumors of the urinary tract were seen more frequently in patients on dialysis. Transplantation and consecutive immunosuppression does not appear to constitute an additional cancer risk for the uremic patient who is faced with the alternative to undergo chronic dialysis or renal transplantation. PMID- 2219567 TI - Effects of various acidic and alkaline solutions used to dissolve urinary calculi on the rabbit urothelium. AB - It is well known that infection-induced stones (apatite, struvite), uric acid and cystine calculi in the urinary tract can be managed by the use of certain chemical solutions. We investigated the effects of various acidic and alkaline solutions on the rabbit urothelium. Acidic solutions (pH: 4.2) caused more urothelial injury as compared to alkaline solutions (pH: 7.6). Ureteral injury was more severe than the bladder injury. Magnesium-containing solutions caused less injury to the urothelium. PMID- 2219568 TI - Precipitation of struvite in urine medium by urease-positive and urease-negative Yersinia strains. AB - Yersinia strains either urease-positive or urease-negative were examined for precipitation of struvite in human urine at 25 and 37 degrees C. All urease positive strains and 8 out of 10 urease-negative strains showed the ability to produce these crystals. Incubation time required for precipitation was longer for urease-negative strains and quantity of struvite formed was higher in urease positive ones. Regarding incubation temperature, no significant influence has been observed. PMID- 2219569 TI - Traumatic dislocation of the testes. AB - Traumatic dislocation of the testis is an unusual disorder. A case of bilateral traumatic dislocation of the testes is presented. Ultrasound examination is very useful for determination of the preoperative diagnosis and management of the dislocated testis. PMID- 2219570 TI - Carcinosarcoma of the spermatic cord. AB - The first case of carcinosarcoma in the spermatic cord is reported in a 40-year old man. The tumor was a 2.5 X 2 cm pseudoencapsulated formation located in the connective tissue of the spermatic cord among the blood vessels. Light microscopy examination of the neoplasm revealed two different histological patterns: epithelial and sarcomatous. Mitoses and atypias were infrequent in both types of areas. The epithelial cells formed papillary and gland-like structures stained with PAS, Hale and mucicarmine stains, and showed positive reaction for immunohistochemical demonstration of both keratin and epithelial membrane antigen. The lumen content of the gland-like structures reacted positively for the carcinoembryonic antigen. Electron microscopy revealed that the epithelial cells were joined by junctional complexes and displayed numerous short microvilli. The sarcomatous areas consisted of spindle cells embedded in a ground substance that occasionally presented myxoid changes. Mast cells and focal calcifications were seen. Sarcomatous cells showed positive reaction for vimentin but not for the other histochemical and immunohistochemical techniques mentioned above. The ultrastructure of sarcomatous cells was similar to that of epithelial cells except for the occurrence of small desmosomes instead of junctional complexes. The differential diagnosis with adenomatoid tumor and malignant mixed mesothelioma is discussed. PMID- 2219571 TI - Early detection and treatment of localized carcinoma of the prostate. PMID- 2219572 TI - Natural history of low-stage prostatic cancer and the impact of early detection. AB - An expanding and increasingly older population, a rising incidence of prostate cancer, and uncertainties regarding treatment effectiveness have made this disease a target of special concern. The natural history of the cancer must be a consequence of host-tumor interactions, but little is known for sure about this subject. The growth rate of the tumor is determined by many factors, including genetic instability. At present, tumor grade, volume, and ploidy are the most useful techniques for judging the growth rate and metastatic potential. Stage A1 tumors generally are indolent, whereas stage A2 tumors are more aggressive. The natural history of stage B lesions is not well documented. The author asks two questions (Is cure necessary in those in whom it may be possible? Is cure possible in those in whom it may be necessary?) and reviews the problems inherent in screening for prostate cancer at this time. PMID- 2219573 TI - Epidemiology of prostate cancer. AB - Available epidemiologic data do not allow targeting of specific populations for prostate cancer screening or early detection programs. Although certain strong factors have been identified (age, race, location), none sufficiently defines high-risk groups in whom recommendations should differ from those of other age matched patients. Certainly, a strong familial tendency has been identified, but the relative contribution of genetic and environmental factors in these patients remains unclear. Some hypotheses on the pathogenesis of prostate cancer are possible based on the available data. Genetic factors appear to be permissive, as are hormonal influences, which are partially regulated by genetics. Environmental factors appear to be promotional in genetically susceptible men. Dietary fat may also be an important promotional factor in genetically susceptible men. Dietary factors appear to exert some influence by modulating sex hormone concentration. Several factors demand more investigation and understanding of the epidemiology of prostate cancer. The relative frequency of the disease and the increasing death rate from prostate cancer are of concern. The similarities in the incidence of latent prostate cancer among various groups with strong differences in the rate of clinically apparent disease raise significant issues regarding potential lifestyle or environmental promotional factors. Further understanding of the pathogenesis of prostate cancer may allow a refinement and definition of programs for prevention and early detection of the disease. PMID- 2219574 TI - Digital rectal examination in the early detection of prostate cancer. AB - Screening using digital rectal examination improves the clinical stage distribution of prostate cancer and prolongs survival. Unfortunately, digital rectal examination may not be sensitive enough to detect the small-volume tumors that are most amenable to cure. In several studies, approximately 50 per cent of cancers detected through screening had already spread beyond the prostate. Regardless, the key to demonstrating overall benefit from screening is a diminished disease-specific mortality rate. To date, this has not been shown. Lower mortality rates from prostate cancer can be demonstrated only through a randomized study comparing screened and unscreened populations. Such a study, which has recently been approved and funded by the National Institutes of Health, will require 10 to 15 years to complete. Until that time, the value of screening for prostate cancer by digital rectal examination or any other method will be unknown. Beyond a lack of proved benefit, screening for prostate cancer may be harmful because of the variable natural history of the disease and the morbidity and mortality rates associated with treatment. There exists a large population of patients with pathologically detectable prostate cancer who will never have clinical disease. The detection of some of these tumors may expose those patients to the risks of unnecessary treatment. Large-scale prostate cancer screening studies may ultimately be shown to be advantageous. The sooner this occurs, the earlier aggressive screening can be advocated, similar to screening for breast cancer. However, the temptation to embark on such screening programs without first demonstrating clear benefit should be resisted. PMID- 2219576 TI - Management of stage A prostate cancer. AB - Transrectal ultrasonography has defined a new category of stage A disease, namely nonpalpable lesions diagnosed by needle biopsy. How this type relates to classic stage A disease is unclear. Stage A1 carcinoma becomes clinically significant only in a distinct minority of patients, and even in this group, progression does not necessarily mean significant morbidity or death from prostate cancer. An aggressive approach is not justified. In contrast, stage A2 cancer is usually virulent, and aggressive therapy with curative intent is justified in patients of appropriate age and health. Both radical prostatectomy and external irradiation appear to provide long-term survival rates superior to those obtained with observation alone, but nearly 20% of these patients will die of cancer despite therapy. Unfortunately, forecasting the outcome in an individual case is still not possible, and efforts to identify prognostic features must continue. In the meantime, emotional arguments in favor of the treatment of all discovered cancers must be suppressed by an informed and objective understanding of the natural history of nonpalpable prostate cancer and the potential impact of treatment. PMID- 2219575 TI - Transrectal ultrasonography for the early detection and staging of prostate cancer. AB - Relatively recent changes and improvements in equipment have vastly increased image resolution for transrectal ultrasonography of the prostate. The expanded use of transrectal ultrasonography has greatly furthered knowledge of prostate zonal anatomy and permitted clinical evaluation of internal prostate architecture. The technique is operator dependent, as the quality of the results is related directly to that person's knowledge and experience. The significant majority of prostate cancers originate from the peripheral zone. Palpable stage B nodules characteristically have a hypoechoic appearance. There is disagreement about the tumor characteristics that cause hypoechogenicity, but large tumors may obscure the normal prostate anatomy and appear isoechoic because of the lack of contrast with surrounding prostate tissue. The transition zone of the prostate is the origin of benign prostatic hyperplasia and almost 20 per cent of prostate cancers. These tumors probably correspond to most stage A lesions. Transrectal ultrasonography is less accurate in identifying transition zone tumors because of the mixed echogenicity of the transition zone, interference from prostatic calculi or calcified corpora amylacea, and poorer image resolution in this area. Studies evaluating the use of transrectal ultrasonography for early detection of prostate cancer generally have shown a twofold increase in the detection rate compared with digital rectal examination. However, the decreased morbidity and expense of transrectal prostate biopsy using an automatic gun device have increased the frequency of biopsy in ultrasound-examined patients compared with those historically evaluated by digital rectal examination. The increased detection rate may in part be a function of the increased use of biopsies, independent of other factors. Transrectal ultrasonography rarely detects cancer in patient with normal digital rectal examination and a normal serum prostate specific antigen level. Transrectal ultrasonography may be capable of identifying early capsular penetration or seminal vesicle invasion in some patients with known prostate cancer. However, its superiority to digital rectal examination for this purpose has not been demonstrated unequivocally. Ultrasonography does allow directed biopsies of the seminal vesicles or other suspect areas, and this may be helpful in staging the disease. The use of transrectal ultrasonography in prostate cancer has evolved rapidly, and changes in technology antiquate reports within a few years.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2219577 TI - Radiation therapy for localized prostate cancer. Justification by long-term follow-up. AB - In the series presented here, survival patterns at 15 years after radiotherapy for patients with clinical stage A carcinoma of the prostate did not deviate significantly from those of an age-matched peer group. For patients with clinical stage B disease (nodular disease that did not exceed involvement of one lateral lobe), survival was only 5% less at 15 years than for the age-matched group of California men. This was in spite of the fact that the lymph node status and the true incidence of capsular penetration were unknown. Moreover, the patients were not stratified by histopathologic grade or by either acid phosphatase or prostate specific antigen values. If one were to restrict the patients to those with intermediate and low Gleason scores, normal acid phosphatase, and low prostate specific antigen values, it is likely that there would have been no difference between the survival of those with prostatic cancer and their age-matched peers. As one deviates from these conservative selection criteria and includes patients with more advanced stages, the likelihood of achieving 15-year survival diminishes. With radiation treatment, however, patients whose disease, by clinical examination, extends beyond the prostate and who seem too advanced for radical prostatectomy still may have a 20 per cent to 30 per cent chance of 15 year survival. PMID- 2219579 TI - Patient selection for, results of, and impact on tumor resection of potency sparing radical prostatectomy. AB - Our results show that by using the nerve-sparing radical retropubic prostatectomy, potency can be preserved in the majority of appropriately selected patients without compromising the adequacy of tumor excision. However, proper patient selection is important. Patients with focal, well-differentiated tumors, especially young patients with stage A or B1 tumors, are ideal candidates. In patients with more extensive and less well-differentiated tumors, there is a higher risk of incomplete tumor excision. Although we suspect that the adequacy of tumor excision is determined more by the extent of the tumor than by the technique of radical prostatectomy used, we believe that nerve-sparing surgery should be used with great caution, if at all, in patients with extensive or high grade tumors. In these patients, microscopic extracapsular tumor extension is extremely common, can be impossible to detect at the time of operation, and is less likely to be adequately encompassed by nerve-sparing techniques. On the other hand, our current data provide little evidence that excision of the neurovascular bundles is beneficial. It is possible that more extensive resections will not materially alter the incidence of positive margins or cure rates. Finally, it might be argued that all forms of radical prostatectomy are inappropriate for patients with poorly differentiated clinical stage B2 prostate cancer for whom there are no really effective treatment options. We continue to recommend radical prostatectomy for these patients based on the finding that patients with clinical stage B2 disease who have organ-confined tumors can be expected to have excellent long-term disease-free survival rates similar to those of clinical stage B1 patients. In the remaining patients who are clinically understaged, the prospects for the minimal microscopic tumor remaining being controlled with adjunctive radiation therapy may be better than those of controlling the bulky primary tumor with radiation therapy alone. This hypothesis will need to be tested in a randomized clinical trial. PMID- 2219578 TI - Significance and treatment of positive margins or seminal vesicle invasion after radical prostatectomy. AB - The periprostatic soft-tissue involvement described in the older urologic literature differs from that now recognized; a much "earlier" pathologic stage C is being identified. Apparent microscopic extension of the cancer to the margin of the specimen yields an approximately 25% risk of local recurrence. Postoperative radiation apparently is effective in reducing this risk, and if patients are properly selected, such treatment is well tolerated. Whether adjuvant radiation affects overall survival is not known. New observations on pathologic extension of the disease need to be refined. PMID- 2219580 TI - The case for no initial treatment of localized prostate cancer. AB - This contribution summarizes the evidence from the natural history and pathology of this disease that, given the high incidence of latent cancer, a policy of radical treatment at diagnosis will represent over-treatment in the majority of cases. As yet, neither radical prostatectomy nor radical radiotherapy has been shown to be effective in managing the poorly differentiated tumor in the patient with "localized" disease. For the patient with well-differentiated disease, there is little evidence that early treatment is mandatory, because the majority of these patients will not die of prostatic cancer. The adoption of a policy of diagnosis followed by active surveillance would spare many patients the hazard and discomfort of a major operation or of a course of radiotherapy, would minimize expenditure, and would ensure that treatment was given only to those patients in whom progression had been demonstrated. Such an approach is almost certain to be as effective as treatment at diagnosis. Confirmation of this view is likely to be obtained from the existing studies of immediate versus delayed orchiectomy or LHRH therapy currently being undertaken by the Urological Working Party of the Medical Research Council in the United Kingdom and the Urological Group of the EORTC within Europe. PMID- 2219581 TI - Local failure and related complications after definitive treatment of carcinoma of the prostate by irradiation or surgery. AB - The authors review their institution's experience with the failure of definitive treatment to achieve local tumor control and with the distant dissemination and local morbidity associated with such failure. The causes of local failure are various: incomplete resection, implantation of spilled cells, and, possibly, selective implantation of circulating tumor cells in traumatized tissues after surgery and totally or partially resistant cells, new tumors, or radiologic misses after radiation. Treatment of local failure may be prophylactic or therapeutic and differs depending on the stage of the disease. Failure to control the tumor locally in the presence of distant metastases does not alter the length of survival, but it can profoundly affect the quality of survival. PMID- 2219583 TI - New concepts in the treatment of stage D1 adenocarcinoma of the prostate. AB - Stage D1 disease will be encountered in 20 per cent of patients by those who treat prostate cancer. There is marked heterogeneity among cancers discovered at this stage, with 5-year disease-free survival rates ranging from 0 to 95 per cent. Generally, when prostate cancer has escaped the confines of the gland, metastasis occurs, and widespread systemic disease prevails. Any significant chance for long-term cure will then depend on systemic therapy. From maturing data in retrospective reviews, preliminary data from prospective trials, and recent well-conducted animal studies, chemotherapy and hormonal deprivation appear most effective when tumor volumes are the smallest. This evidence supports the removal of all cancer possible and the early institution of systemic treatment. Caution must be exercised in extrapolating the aforementioned evidence to include cases of more extensive prostate cancer (i.e., patients with bulky pelvic or retroperitoneal disease, distant metastasis, or significant elevation of serum markers). It is doubtful that "debulking" with removal of the prostate and lymph nodes will provide any justifiable advantages in these patients. Whether removal of the prostate affords any local palliative benefit is an issue for debate. Certainly, the primary tumor, if left untreated, will progress locally and cause symptoms necessitating further procedures in more than half these patients, whereas the incidence of local recurrence and the adverse effects of these recurrences in patients with D1 disease after radical prostatectomy and adjuvant therapy is less than 10 per cent. Surgical refinements coupled with acceptably low morbidity now associated with radical prostatectomy have led some authors to endorse the palliative benefits of removing the primary tumor in selected patients. The purpose of this article is not to endorse or disparage the aggressive treatment of patients with stage D1 prostate cancer. The evidence suggests that if long-term survival is the endpoint used to compare treatment groups, then to date no treatment option offers significant advantages. On the contrary, if progression rates or disease-free survival are compared, then cytoreductive surgery and early systemic adjuvant treatment (testosterone deprivation or chemotherapy) provides significant advantages for selected patients with stage D1 disease. Although ploidy analysis, receptor mapping, and oncogene assays are promising, today, there is no practical way to identify patients who will benefit most from multimodality treatment approaches.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2219582 TI - Current options in the management of clinical stage C prostatic carcinoma. AB - The evaluation of clinical stage C prostatic cancer has been enhanced by advances in staging modalities over the past 15 years. Better staging of the local lesion is possible with transrectal ultrasound-guided multiple biopsies of the prostate and its vicinity. Biopsies of suspect pelvic lymph nodes guided by CT (or lymphangiography) may obviate pelvic lymphadenectomy, particularly in patients with high-grade stage C lesions. Advances in the understanding of serum markers have supplemented other staging information. No single therapeutic modality is appropriate for all cases of clinical stage C cancer. In C1 lesions, radical prostatectomy with adjunctive radiation or hormonal therapy seems to produce the best 5- and 10-year survival rates. External-beam radiation alone, or in combination with interstitial radiation, may have equivalent success. In clinical stage C2 disease, external-beam radiotherapy seems at present to be the best therapeutic modality. Interstitial radiation as a sole method of management in stage C disease carries a high local recurrence rate and a significant risk of metastatic progression. Transurethral prostatectomy and hormonal treatment continue to have a place in the management of selected poor-risk patients. The current results with surgery or radiation therapy alone are less than ideal. It is recommended that aggressive combination treatment be compared with monotherapy in randomized clinical trials monitored jointly by radiation and urologic oncologists. PMID- 2219584 TI - Flow cytometry in carcinoma of the prostate. AB - Flow cytometry is a quantitative cytologic technique with demonstrated utility in the assessment of prostate cancer as well as other tumors. The authors summarize current data on its use in disease detection and diagnosis, prognostic evaluation, and monitoring of response to therapy. They also project future developments. PMID- 2219585 TI - Current management of varicoceles. AB - In spite of all that has been written about the varicocele, it is still not clear who will benefit from occlusion of the spermatic vein or why improvement in semen takes place in some patients but not in others. Because fertility is usually assessed in the framework of a couple who are trying to establish a pregnancy, it is important to evaluate both partners before making any recommendations regarding therapy. If the man is found to have a varicocele and semen analyses that indicate deficits in either the quantity or quality of the sperm, surgical ligation or transvenous occlusion should be considered as one appropriate form of therapy. Varicocele ligation and embolotherapy both can be performed as an outpatient procedure with minimal morbidity and equal effectiveness regarding pregnancy outcome. The cost, if the procedures are done in an outpatient facility, should be approximately equal. The obvious benefits of the percutaneous technique are a slightly lower recurrence rate and a more rapid return to full physical activity. The surgical procedure described by Marmar and associates appears to have a similar rate of recurrence and short postoperative period of recovery. Greater experience by more urologists using this technique needs to be gained to compare it adequately with the other methods described. Varicocele ligation by the inguinal or retroperitoneal routes is familiar to most urologists and does not require the operating microscope or other special instruments. With greater understanding of the venous anatomy and with careful dissection, the persistence and recurrence rate can be acceptably low and the postoperative recovery relatively rapid and smooth. PMID- 2219586 TI - Enhanced in vivo cytotoxicity of recombinant human tumor necrosis factor with etoposide in human renal cell carcinoma. Evaluation in a pre-clinical model. AB - The combination of tumor necrosis factor (TNF) and etoposide (ETP) was evaluated for potential cytotoxic efficacy against a human renal cell carcinoma xenograft using an in vivo assay employing an athymic mouse host with tumor implanted a the subrenal capsule site. Both antitumor efficacy (relative survival or RTS) and toxicity (weight loss) of TNF and ETP alone and in combination were evaluated. While TNF and ETP alone were mildly inhibitory (RTS 90% and 71%, respectively), the combination caused marked tumor inhibition (45% of controls). Host toxicity encountered with the combination did not exceed the toxicity associated with ETP alone, suggesting that the therapeutic index may have been augmented. It is concluded that enhanced antitumor activity without substantial augmentation of toxicity is observed with this combination, providing a rationale for further evaluation of tumor necrosis factor-based regimens for the treatment of advanced renal carcinoma. PMID- 2219587 TI - Expression of ras gene family as result of compensatory renal growth in mice. AB - We have examined several gene expressions during the process of compensatory renal growth in mice following unilateral nephrectomy. On the 3rd, 5th and 7th days after operation in young mice (age: 5w), unilateral nephrectomy induced weight gain of the remaining kidney, but not in adults (age: 15w). It also induced maximum expression of c-H-ras and c-K-ras on the 3rd day in both young and adult mice, but there was no increase in N-ras in either. The expression levels of c-H-ras and c-K-ras were higher in young mice than in adults. However no expression of c-myc was detected at any point. Expression of metallothionein-I (MT-I) gene was detected during the first 12 h after unilateral nephrectomy both in the liver and the contralateral kidney. These data suggest that c-H-ras and c K-ras gene expressions are in some way related to compensatory renal growth in mice and may be strongly related to hyperplasia in the contralateral kidney. PMID- 2219588 TI - Damaging effects of high energy shock waves on cultured Madin Darby canine kidney (MDCK) cells. AB - Shock wave lithotripsy (ESWL) has become an almost non-invasive standard treatment modality for urolithiasis. Several investigations, however, demonstrated that ESWL is not completely free of side effects. Among others alteration of renal tubular function has been reported. To study the effect of shock waves on tubular cells directly an in-vitro model with cultured Madin Darby Canine Kidney (MDCK) cells was established. Suspensions of MDCK cells (7 groups of 6 containers each) were exposed to 0, 16, 32, 64, 128, 256 shock waves (Dornier HM4, 18 kV). Before and 0, 1, 3, 6, 9, 12, 24 h after ESWL the following parameters were measured in the nutrient medium: lactate dehydroxygenase (LDH), glutamate oxalacetate transaminase (GOT), electrolytes. LDH and GOT increased depending on the number of shock waves indicating a membrane damage of MDCK cells. The MDCK model seems suitable for further studies on the effect of shock waves on renal tubular cells. PMID- 2219589 TI - Ultrastructural visualization of human bladder mucous. AB - Mucous within the urinary bladder appears to play a protective role in shielding the uroepithelium against pathogens. This present study employs specific anti mucous, antisera stabilization techniques to visualize a thin, continuous layer of mucous closely adherent to the human bladder uroepithelium, in both scanning and transmission electron microscopic analyses. PMID- 2219590 TI - Anti-tumor effect of intravesical instillation of OK432 against rat bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. AB - The anti-tumor effect of OK432 instilled into the bladder was evaluated in rat bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). In experiment I, the rate of the natural killer (NK) activity was determined with cells from spleen and mesenteric lymph nodes. Intravesical OK432 instillation enhanced NK activity; however, this activity was not dose-dependent and was not augmented by OK432 inoculation into the foot pad. In experiment 2, the therapeutic effect of intravesical OK432 instillation was examined in rat bladder tumors induced by BBN. OK432 was instilled weekly for six weeks. Rats given BBN for 10 weeks were divided into six groups: 1) control; 2) saline; 3) OK432 0.05 KE/ml; 4) OK432 0.05 KE/ml bladder instillation with 0.01 KE/ml foot pad inoculation; 5) OK432 0.05 KE/ml, every other week; and 6) OK432 0.5 KE/ml. Weekly OK432 instillation significantly reduced tumor weight and the incidence of tumor development; however, this inhibition was not dose-dependent and was not enhanced by OK432 inoculation into the foot pad. In rats given OK432 weekly, the augmentation of NK activity and increase in tissue infiltrating lymphocytes were significant. These results suggest that intravesical OK432 instillation is effective in the management of superficial bladder tumors. The study further emphasizes that the dose and method of administration are critical variables in determining the efficacy of immunotherapy. PMID- 2219591 TI - Effects of alpha-difluromethylornithine on the development of deeply invasive urinary bladder carcinomas in mice. AB - alpha-Difluoromethylornithine (DFMO), was examined for its ability to suppress the development of invasive urinary bladder carcinoma in C3H/He male mice. Continuous administration of 0.2% DFMO in water following carcinogen treatment (0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine, BHBN, in drinking water for 8 weeks) was effective in suppressing urinary bladder carcinomas (P less than 0.05) as compared with the control group. However, when comparison was made based on tumors involving the entire urinary tract, protective effects could not be demonstrated. Coadministration of DFMO (0.2%) and BHBN (0.01%) did not alter tumor induction by the latter. These results were in sharp contrast to the protective effects in rats. Since bladder tumors in rats are of low grade and superficial whereas those in mice are of high grade and deeply invasive, our data indicate that DFMO has little to no effects against the development of aggressive forms of bladder carcinoma. PMID- 2219593 TI - In vivo effect of 5 French bipolar and monopolar electrosurgical probes on the porcine bladder. AB - Previous in vitro studies have indicated bipolar electrosurgical probes would electrodesiccate tissue in a normal saline solution. This study applies similar sized monopolar and bipolar electrosurgical probes to porcine bladder in order to compare each probe's effect in vivo. The power delivered by each probe was calculated; the width and depth of the porcine bladder damage was measured and the volume of the damage calculated. The animals were sacrificed at 24, 48 and 96 h post-procedure so that the amount of tissue destruction could be quantitated relative to the bladder's natural tissue reaction. The data shows the power (watts) delivered by the monopolar probe to be approximately six times that of the bipolar probe. Likewise, the area of bladder wall damage was larger with monopolar at all time periods sampled and showed significant differences at 24 and 48 h. These studies indicate that in viable bladder, tissue bipolar probes will electrodessicate at a lower power and with less shortterm tissue damage. PMID- 2219592 TI - Absence of structural alterations of the multidrug resistance genes in transitional cell carcinoma. AB - Tumor DNA from 27 patients with treated or untreated transitional cell carcinomas of the urinary tract was screened for genomic alterations of the multidrug resistance genes in order to determine whether structural changes of these genes are important in primary urothelial tumors. None of the tumors showed evidence of amplification or rearrangements of either mdr1 or mdr2. The lack of amplification or rearrangements observed in these tumors suggests that structural alterations of the mdr1 and mdr2 genes are not important mediators of drug resistance in TCC. PMID- 2219596 TI - [Traumatology in urology]. PMID- 2219595 TI - [Tumors in childhood. II. Neuroblastoma]. PMID- 2219594 TI - Transforming growth factor beta-like activity in human hydrocele fluid. AB - In this study transforming growth factor beta (TGF-beta)-like activity in human hydrocele fluid was investigated. Inhibition of DNA synthesis of adult rat hepatocytes in primary culture and stimulation of colony formation of normal rat kidney (NRK) fibroblasts, clone 49F in soft agar were observed in all acidified hydrocele fluids and these activities were neutralized by the specific antibody raised against human native TGF-beta. In samples obtained from recurrent cases of hydrocele, TGF beta-like activity was observed in its active form (without acidification). These results suggest that human hydrocele fluid contains TGF beta-like activity and that the active form of TGF-beta in recurrent hydrocele fluid may be responsible for the recurrence of the disease even after repeated aspiration. PMID- 2219597 TI - [Injuries of the urogenital system]. AB - Ultrasonography is accepted as a valuable screening method for the detection of renal trauma, although it does not make any functional contribution. Computerized tomography has replaced excretory urography for the evaluation of blunt renal trauma, because it makes more precise diagnosis possible. Arteriography is mandatory when injuries of the renal branch are suspected. The management of renal trauma should restore normal circulation and renal function and should preserve as much functioning renal tissue as possible. For renal contusion and minor cortical lacerations, even when there is a small extravasation of urine, conservative management is sufficient, while major cortical lacerations and injuries of the renal vessels require prompt operative methods. The classification of urethral ruptures is based on rectal palpation of the prostate, distribution and size of hematomas and urethrography. A primary catheter for diagnostic purposes is strictly contraindicated. Urinary diversion proximal to the urethral lesion is the primary therapeutic procedure, while the definite management of the ruptured urethra can be postponed. Injuries to the organs of the urogenital system are rarely life threatening, and in the case of multiple trauma their management can be adapted to fit in with the treatment of injuries to other vital organs. Nevertheless, diagnosis and adequate treatment of injured urogenital organs must not be neglected as long-lasting or permanent damage could result. PMID- 2219598 TI - [Results of the West German multicenter study "Urological traumatology"]. AB - The West German Multicenter Study on Urological Traumatology ran from April 1984 to December 1986. During this time, 19 departments of urology evenly scattered over the Federal Republic of Germany including Berlin (West) recorded and evaluated the data pertaining to a total of 385 patients (83% male, 17% female) with urogenital trauma. The distribution of the different mechanisms of injury demonstrates that 41% were due to traffic accidents; 13% each to accidents during sports and work; 8% to sexual activities; and 6% to violence. The trauma was slight in 40% of the cases, moderate in 21%, and severe in 39%. Of a total of 427 urogenital injuries, 27% were combined with intra-abdominal and 24% with pelvic injuries. Renal injuries were recorded in 51%, ruptures accounting for 49% of these and contusions for 48%. Hilar lesions were observed in 7%, with complete destruction of the organ occurred in 6% of these cases. In all, 76% of these traumas were treated conservatively, while 8% each required surgical reconstruction and nephrectomy. Traumatic lesions of the urinary bladder, urethra, penis, and scrotum including the testes and accessory organs were recorded in about 10% each. Macrohematuria was seen with 73% of renal, 83% of urinary bladder, and 73% or urethral injuries. Microhematuria occurred with 24%, 9%, and 13% of all cases, while no hematuria was ascertained in 3%, 5%, and 13% of renal, bladder and urethral traumas, respectively. The injury-related sensitivity of the different imaging methods was calculated at 95% for cystograms, 91% for retrograde urethrograms, and 83% for angiograms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2219599 TI - [Late sequelae after urogenital trauma. Results of follow-up studies]. AB - In the course of the Multicenter Study on Urological Traumatology ("UMCEST"), 61 patients who had been treated at the Departments of Urology of the Ludwig Maximilian University in Munich and the Heinrich Heine University in Dusseldorf were followed up. These included 39 patients with multiple trauma and 22 patients who had suffered isolated urological injuries. There were 45 patients with renal injuries, 7 with injuries to the bladder, and 11 who had presented with urethral injuries. Late complications were detected in 38% of the 45 patients with renal injuries. Of the 11 patients with urethral injuries, 6 suffered from urethral strictures, 9 from sexual dysfunction and 3 from incontinence. The 7 patients with bladder injuries had no late complications related to the bladder trauma. PMID- 2219600 TI - [Spontaneous kidney rupture]. AB - Two cases of spontaneous rupture of the kidney are reported and the literature is reviewed. The clinical and pathological features of this uncommon disease and its treatment are discussed. In the first case the cause of retroperitoneal bleeding was a renal carcinoma, while in the second it was the result of renal metastases from gestational trophoblastic disease. The most common symptoms are an acute onset of flank or abdominal pain, macroscopic hematuria and a drop in the hemoglobin level. Resistance or a mass can be palpated. Ultrasound and radiological examinations allow visualization of a tumor or hematoma and mostly reveal the etiology of hemorrhage. An exploratory operation is necessary for diagnosis, and primary nephrectomy should be seriously considered. PMID- 2219601 TI - [The value of surgical therapy in the treatment of urogenital tuberculosis]. AB - A series of 94 patients treated over a period of 22 years for genitourinary tuberculosis is reviewed. The group was made up of 72 patients with isolated urinary tuberculosis, 12 with isolated tuberculosis of the genitalia and 12 with combined disease. In 70 patients surgery was performed in addition to the standardized chemotherapy. Of the 72 patients with urinary tuberculosis, 21 received exclusively conservative treatment, while 16 underwent conservative surgery and the remaining 35, ablational surgery. The high nephrectomy and overall operation rate is explained by the high percentage of advanced state of disease and a large number of patients referred to us for nephrectomy following long-term conservative treatment. A retrospective justification for this procedure is found in the fact that 52% of the surgical specimens showed florid tuberculosis though the patients had been receiving standardized chemotherapy for an average of 9 months. PMID- 2219602 TI - [Urological aspects of non-urological tumor in the lesser pelvis]. AB - The surgical outcome in 30 patients with advanced pelvic malignancies of nonurological origin infiltrating the urinary tract was analyzed. The pelvic mass was totally removed by multivisceral resection in 15 patients, and incompletely removed in 11 patients; 4 patients underwent only palliative treatment in the form of urinary diversion, because of unresectable tumors. Mortality, morbidity, survival rates and quality of life were evaluated and showed significant differences. The best results were achieved in the group with complete excision of pelvic viscera. Patients treated with incomplete resection or palliative urinary diversion because of unresectable mass had a poor outcome. PMID- 2219603 TI - [Ambulatory carboplatin monotherapy in advanced seminoma]. AB - Six patients with advanced seminoma (stage IIc) received single-agent carboplatin therapy. The drug was administered to outpatients without prior hyperhydration. All five patients who completed the regimen of three to four cycles achieved complete remission, which was confirmed histologically in four patients by retroperitoneal lymph node dissection. No severe side-effects were observed. Single-agent carboplatin therapy is a highly efficient regimen with very little toxicity. This treatment seems to be the therapy of choice in patients with advanced seminoma. PMID- 2219605 TI - Low incidence of asymptomatic brain metastases in patients with renal cell carcinoma. AB - Brain metastases from renal cell carcinoma are uncommon. The present study was undertaken to determine the value of routine computerized tomographic (CT) scanning of the brain in patients with renal cell carcinoma. A review of 106 patients with renal cell carcinoma who had undergone CT scan of the brain revealed brain metastases in only 13.2 percent. Brain metastases were accompanied by central nervous system (CNS) symptoms in 78.6 percent of patients, with headaches constituting the most common presenting symptom (64.3%). Brain metastases were detected in only 3.3 percent of patients who had no CNS symptoms at the time of evaluation. It is concluded that CT scanning of the brain should be performed routinely only for those patients who report CNS symptoms at the time of evaluation. PMID- 2219604 TI - [Asymptomatic paraganglioma of the bladder wall with unusual extensive submucous vascular proliferation]. AB - Paraganglioma of the urinary bladder is a very rare tumor, which is usually diagnosed on the basis of its endocrine symptoms because of the excretion of vasoactive substances. One case of asymptomatic paraganglioma detected by chance is described, it was misdiagnosed as hemangioma because of its marked suburothelial vessel proliferation. PMID- 2219606 TI - Is urethral sparing at cystectomy a safe procedure? AB - Urethrectomy is performed with cystectomy when the neoplasm is multifocal, at the bladder neck, or associated with carcinoma in situ (CIS). The records of the most recent 20 patients treated by radical cystectomy at our institution were reviewed. In 50 percent of the cases, the extent of disease within the bladder was found to have been underestimated to the point that a urethral sparing operation (i.e., to maintain urinary continence with an intestinal segment and an intact urethra) might have been dangerous. PMID- 2219607 TI - Neodymium:YAG laser treatment of bladder hemangiomas. AB - We present 3 cases of bladder hemangiomas, one single and two multiple, with a long-term history of recurrent hematuria, treated with endoscopic neodymium:YAG (yttrium, aluminum, garnet) laser photocoagulation, and obtaining good results. PMID- 2219608 TI - Allopurinol and thiazide effects on new urinary stone formed after discontinued therapy in patients with urinary stones. AB - We treated 87 patients with calcium-containing urinary stones with either allopurinol alone (44 patients) or in combination with thiazide (43 patients) and studied new stone formation before, during, and after the discontinuation of the drug therapy. The number of stones formed were 1.18, 0.24, and 0.13 before, during, and after discontinuation of the drug therapy, respectively, in the patients treated with allopurinol alone and 1.32, 0.20, and 0.09 in those treated in combination with thiazide. No differences were observed in these values and the duration of each observation period between the two groups. Decreases in the incidence of stone formation even after interruption of drug therapy suggested that recurrence-preventive effects observed following administration of these drugs include the effects of medical guidance. However, allopurinol therapy was effective in preventing recurrence in patients with hyperuricosuria. PMID- 2219609 TI - Squamous cell carcinoma antigen (TA-4) in penile carcinoma. AB - TA-4 antigen, originally isolated from women with squamous cell carcinoma of the cervix, is elevated in the sera of patients with squamous cell carcinomas of several sites, including esophagus, lungs, and head and neck. In this study, we compared the serum levels of TA-4 in normal volunteers, patients with resected penile squamous cell carcinoma, and patients with metastatic penile squamous cell carcinoma. TA-4 values were elevated in 5 of 11 patients (45%) who had metastatic disease. In 2, TA-4 was normal the first time metastasis was clinically detected but rose as the disease progressed. Moreover, in 3 patients in whom serial determinations were made, serum TA-4 values correlated well with disease progression and response to treatment. We conclude that TA-4 values are elevated in some patients with metastatic squamous cell carcinoma of the penis and may become a useful marker for monitoring response to therapy. PMID- 2219610 TI - Management of penile gunshot wounds. AB - The management of 10 cases of penile gunshot wounds treated at Henry Ford Hospital from 1982 to 1986 is reviewed. All patients were assaulted by low velocity weapons (handguns). Eight patients had associated injuries, predominantly to the genital region (thigh, pubis, and scrotum). There were 5 urethral injuries; 4 were treated with primary repair, the remaining patient underwent delayed repair, complicated by severe urethral strictures requiring reoperation. Blood at the urethral meatus was suggestive of urethral injury but microscopic hematuria was not. Five penile injuries did not involve the urethra and were treated by debridement and primary wound closure with no immediate or delayed complications. In dealing with these injuries we recommend a high index of suspicion for urethral and regional organ injury and primary urethral closure if at all possible. PMID- 2219611 TI - Sex reversal syndrome (XX male). AB - Men who appear normal and live a normal life, may have a 46,XX karyotype and present with the typical features of infertility and end organ (testicular) failure. They are azoospermic and their small testicles show specific patterns on light and electron microscopy. Recent advances in genetics (1) favor the "X-Y interchange" theory to explain this phenomenon; (2) hypothesize about the roles of the H-Y antigen and testis determining factor (TDF) in determining "maleness"; and (3) allow mapping of the relative positions of H-Y and TDF loci on the Y chromosome. PMID- 2219613 TI - Triorchidism--a reconstructive approach. AB - Testicular duplication is a relatively rare condition. A case is described in which conservative surgery was performed with reconstruction to produce a single testis. PMID- 2219612 TI - Renal abscess in children. AB - Three cases of renal abscesses in children are described to illustrate the variable presenting features. An additional 23 pediatric cases, reported over the past ten years, were reviewed for clinical features and therapy. Fever, loin pain, and leukocytosis were common presenting features, but less than half of all abscesses were associated with either an abnormal urinalysis or a positive urine culture. The presenting features were sometimes confused with appendicitis, peritonitis, or a Wilms tumor. An organism was identified in 17 cases- Escherichia coli in 9 children and Staphylococcus aureus in 8 children. The majority of E. coli infections occurred in girls and the majority of S. aureus infections occurred in boys. Reflux was documented in 5 patients, and 2 children had a possible extrarenal source of infection. Antibiotics alone produced a cure in 10 children (38%), but 16 children (62%) required a surgical procedure. PMID- 2219615 TI - Inverted papilloma of renal pelvis: flexible ureteroscopic diagnosis and treatment. AB - A case is reported of inverted papilloma of the renal pelvis in a patient with previous transitional cell carcinoma of the bladder. The renal pelvic lesion was diagnosed and treated with a flexible ureteropyeloscope. Although nephroureterectomy was avoided, the patient must be carefully followed endoscopically and radiographically for recurrence of lesions throughout the urinary tract. This case represents the first report of the endoscopic diagnosis and treatment of an inverted papilloma of the renal pelvis. It demonstrates the vast potential for endoscopic diagnosis, treatment, and surveillance throughout the urinary tract. PMID- 2219614 TI - Treatment of primary nocturnal enuresis by oral androgen mesterolone. A clinical and cystometric study. AB - A double-blind clinical study of 30 boys, six to ten years of age, with primary nocturnal enuresis was undertaken to assess the role of androgens in treating enuresis. The oral synthetic androgen mesterolone was selected because of its minimal potential toxic effects. Twenty boys were treated with mesterolone and 10 received placebo. Fourteen boys (70%) became dry during treatment (20 mg daily for 14 days), and 5 (25%) remained dry for a follow-up period of four months. Increased cystometric bladder capacity and disappearance of uninhibited detrusor contractions were noticed in a significant number of cases after treatment. No side effects were recorded. Mesterolone has probably modulated the autonomic innervation of the vesical musculature with correction of the defective neural mechanism which is believed to be implicated in the pathogenesis of nocturnal enuresis. PMID- 2219616 TI - Improved early detection of recurrence in prostatic carcinoma following hormonal therapy. Combined use of palpation and fine needle aspiration cytology. AB - Fifty-nine hormonally treated prostatic carcinoma patients were prospectively followed by rectal examination and fine needle aspiration cytology at six-month intervals for periods ranging from six to one hundred twenty months (median follow-up 48 mos). The cytologic findings and clinical impressions were divided into four or five categories, respectively, ranging from benign to clearly malignant. Cytologic material and clinical descriptions suitable for evaluation were available for 306 follow-up examinations. Of these, 209 were cytologically benign (including 191 without and 18 with clinical evidence of malignancy). The remaining 97 examinations showed cytologic evidence of malignancy of which 50 were clinically apparent (51.5%). While the correlation of clinical and cytologic findings was good (91.4%) in cases with no evidence of disease activity, our findings indicate that many recurrences which are occult to clinical examination may be detected by cytologic examination. PMID- 2219618 TI - Urothelial grafts in mice. AB - Mouse bladder epithelium has been successfully transplanted to the bladders of syngeneic mice and has survived for at least twenty weeks. The fate of the transplanted tissue was followed using a fluorescein label. The recipient bladders were prepared by stripping the urothelium either by a surgical or a chemical method. The possibility of adopting a comparable technique for the treatment of early bladder cancer in man is discussed. PMID- 2219619 TI - Acute aluminum toxicity after continuous intravesical alum irrigation for hemorrhagic cystitis. AB - An encephalopathy and cardiomyopathy developed in a seventeen-year-old girl with chemotherapy-induced renal failure while receiving an intravesical aluminum infusion for hemorrhagic cystitis. Premortem serum and postmortem tissue aluminum levels were markedly elevated. It is likely that her inability to excrete absorbed aluminum contributed to her death. Aluminum infusions should be used with caution in patients with renal failure. PMID- 2219617 TI - Staging of ureteral transitional cell carcinoma by CT and MRI. AB - Intravenous urography and retrograde pyelography are the primary radiologic studies for detecting ureteral carcinoma but give limited information regarding stage of disease. Computed tomography (CT) and magnetic resonance imaging (MRI) delineate the extent of ureteral carcinomas with a high degree of accuracy by depicting the periureteral fat and presence or absence of lymphadenopathy. In selected cases, CT and MRI are valuable for assessing the presence or absence of tumor in a ureteral stump and for the differential diagnosis of ureteral obstruction. Five cases of ureteral carcinoma and 2 cases of stump carcinoma are presented with preoperative CT and/or MRI evaluation and staging. PMID- 2219620 TI - Mumps orchitis. PMID- 2219621 TI - Uneventful delivery following series of successive treatments for virilized Cushing syndrome due to adrenocortical carcinoma. AB - A twenty-one-year-old virilized woman with Cushing syndrome due to a huge adrenocortical carcinoma was successively treated with trilostane (3 beta hydroxysteroid dehydrogenase inhibitor), subsequent adrenalectomy, and postoperative cis-platinum. Clinical or biochemical abnormalities peculiar to Cushing syndrome gradually subsided, and three and one-half years after the adrenal surgery, the patient delivered a normal female infant. This study points out some of the clinical and biochemical responses of each treatment. PMID- 2219622 TI - Single polypoid cystitis cystica and glandularis presenting as benign bladder tumor. AB - A case report of a ten-year-old boy with a benign polypoid bladder tumor is presented. The rarity of benign or malignant bladder tumors in children is reviewed, as well as the possible etiology of this unique lesion. PMID- 2219623 TI - Controlled vacuum chamber for standardized photographic documentation of penile erectile deformity. PMID- 2219625 TI - [The genetic contribution of cows to the prevalence of mastitis in the following generation]. AB - Investigations of mastitis prevalence were performed in 1227 dam-daughter pairs during 1985-1988. From the records of the last 10 years, the findings concerning mammary gland were obtained. Six herds of agricultural co-operatives in the Brno region were investigated. In the early period the Bohemian Pied breed, later the crosses of this breed with Red Holstein and a low genetic proportion of Ayrshire cattle, dominated in the set of cows. Udder health was assessed using the clinical and bacteriological findings in individual udder quarters and the results of the rapid mastitis test NK. Based on this data, the cows were divided into two groups--resistant and susceptible. The lactation order in which the disease appeared for the first time was of great importance. The occurrence of the disease in daughters and udder health in dams were in a significant relation (P less than or equal to 0.01). While nearly 50% of daughters of susceptible dams were affected, it was only 25% in daughters of the resistant group. The assessment of heritability of resistance to mastitis was carried out on the principle of dam-daughter regression. The index of heritability h2 = 0.52 +/- 0.06 was calculated. The results show that the genetic contribution of dams to the susceptibility of daughters to mastitis is significant. PMID- 2219624 TI - Transitional cell carcinomatous meningitis after M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy. AB - The M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen has been utilized at our two institutions to treat 17 patients with advanced stage transitional cell carcinoma of the bladder. We report 2 cases of carcinomatous meningitis resulting from metastatic transitional cell carcinoma which occurred in patients treated with M-VAC. Review of the literature suggests that our experience with central nervous system metastases is not unique, and that treatment of advanced stage transitional cell carcinoma of the bladder with M-VAC may enhance the incidence of meningeal metastases. Carcinomatous meningitis, although rare, is a rapidly fatal manifestation of metastatic transitional cell carcinoma if left untreated. However, prompt diagnosis and early aggressive therapy may result in palliation and stabilization of neurologic status. We review the pathophysiology, diagnosis, and treatment of transitional cell carcinomatous meningitis. PMID- 2219626 TI - [Determination of beta-lactamase production in strains of Staphylococcus aureus isolated from the milk of cows]. AB - Determination of sensitivity to penicillin G by a standard disk assay diffusion method was compared with a iodometric method of test papers to determine beta lactamase production after Jorgensen in Staphylococcus aureus strains isolated from cow's milk from different farms. Out of 179 test strains, 32 strains 17.8%) were found to be well sensitive in the diffusion test; eight of these strains (25.0%) were demonstrated to produce beta-lactamase. 54 strains (30.2%) were sensitive. 27 strains (50%) of this group produced beta-lactamase. 93 strains (51.9%) were resistant to penicillin G in the diffusion test. 86 strains (92.5%) were found to produce beta-lactamase and seven strains were negative in this test. Using the diffusion test of sensitivity in these cultures, 86 strains were sensitive (48.1%) and 93 strains were resistant (51.9%). Beta-lactamase was produced by 121 strains (67.6%) and no beta-lactamase production was recorded in 58 strains (32.4%). Differences in the results of both tests were manifest mainly in the set of strains qualified as sensitive (inhibition zone diameter 24 to 16 mm) and well sensitive (inhibition zone diameter larger than 25 mm). The results indicate that the currently performed diffusion test of sensitivity to penicillin G should be accompanied by an assay of beta-lactamase production. The iodometric method of test papers is simple, rapid and cheap and can be made in any bacteriological laboratory. The high resistance of Staphylococcus aureus strains to penicillin G documents that this antibiotic is little efficient in the treatment of mastitis of this etiology in the given region. PMID- 2219627 TI - [Alkaline phosphatase activity in goblet cells in the small intestine of piglets experimentally infected with the coccidium Isospora suis]. AB - Alkaline phosphatase activity (EC. 3.1.3.1.) in goblet cells was investigated in the small intestine of 16 gnotobiotic piglets infected one day after delivery (DAD) by different rates of oocysts of Isospora suis coccidia. At a high infection rate of I. suis (750,000) the goblet cells were found to be highly positive to alkaline phosphatase on day 3 to day 4 after infection (DAI). In piglets infected by a low infection rate of I. suis oocysts (100,000) the activity of alkaline phosphatase activity in goblet cells was proved on days 4 to 10 after infection. In the first group of piglets, the positive goblet cells prevailed in the middle region of jejunum, with the peak on 4th DAI. It the second group of piglets a marked increase in the alkaline phosphatase activity was recorded in the goblet cells in the posterior part of jejunum on days 4 to 5 after infection and on 10th DAI. No alkaline phosphatase activity in the goblet cells was demonstrated in the control gnotobiotic piglets at the age of two to seven days. PMID- 2219628 TI - [Superovulation induction in sheep using PMSG]. AB - The effects of application of differentiated PMSG rates (Antex Leo, Denmark) were investigated in 30 ewes of the Slovak Merino breed in the period of May--June in experimental conditions on the induction of superovulation and on the speed of egg transport through the sexual organs. After administration of PMSG at rates of 750, 1000 and 1500 i. u. per head/day, increases were recorded in the average weight of ovaries, number of large follicles and ovulations. Flushing the eggs from different parts of the sexual organs indicated that the higher the PMSG rate, the faster was the egg transport. PMID- 2219630 TI - Veterinary research--an exciting muddle. PMID- 2219629 TI - [The ependymal lining of the median eminence in goats]. AB - Ependymal epithelium of eminentia mediana in goats, examined under a light microscope, was found to be formed by beta 2 tanycytes, basal processes reaching the surface of zona externa and bifurcating in zona interna. The thickest is zona interna, consisting of dense fibres of different arrangement. A scanning electrone microscope revealed that the structure of the ependymal surface of eminentia mediana in goats depends on the phase of sexual activity of a given individual. In female and male animals the findings are almost identical (ependymoresorption is prevailing) in the period of quiescence (anoestrus, out of the season, April); an analogical situation was observed in females and males in the period of mating (hyperependymosecretion, October, November). The ependymal surface of eminentia mediana in female animals has also a typical structure in the preparatory pro-estrous stage of sexual cycle, when the results were almost identical with those in a hermaphrodite (secretion and resorption are almost equilibrated). The occurrence of supraependymal cells on the surface of eminentia mediana is scarce. These cells are very similar to nerve cells as to their external morphological structure. The presence of supraependymal fibres on the surface of the bottom of the IIIrd cerebral ventricle can be explained only partly by the finding of supraependymal cells. The investigations revealed that the structure of the surface of the ependymal epithelium of eminentia mediana in goats is markedly differentiated according to the sex; this confirms the participation of tanycytes in the control of the reproductive cycle. PMID- 2219631 TI - Ten cases of bladder paralysis associated with sabulous urolithiasis in horses. AB - Bladder paralysis and sabulous urolithiasis were diagnosed in 10 horses with urinary incontinence. Additional neurological deficits in the hindquarters were detected in five of them. Treatment by catheter drainage and bladder lavage was unsuccessful, and all the horses were destroyed within 14 months of presentation. Neuritis of the cauda equina was diagnosed post mortem in one horse, but the cause of the paralysis was not identified in the others, although radiography revealed abnormal lumbosacral vertebral angulation in one case. PMID- 2219632 TI - A question of judgement. PMID- 2219633 TI - Animal identification. PMID- 2219634 TI - Dystocia in Friesian heifers. PMID- 2219635 TI - Klebsiella pneumoniae infection in chinchillas. PMID- 2219636 TI - Terminal ileitis in lambs. PMID- 2219638 TI - RAVC director. PMID- 2219637 TI - Blood sampling bitches for pregnancy tests. PMID- 2219639 TI - Sale and supply of veterinary medicines. PMID- 2219640 TI - Use of a uterine pessary to prevent infection of the uterus of the cow after parturition. AB - A uterine pessary containing penicillin, streptomycin, formosulphathiazole and ethinyloestradiol, was assessed for its efficacy in reducing the frequency and severity of uterine infections in cows after parturition. Fifteen pluriparous Holstein Friesian cows had pessaries inserted into the uterus within 24 hours after calving. Compared with 14 similar untreated cows there were significant reductions in the number infected by Actinomyces pyogenes and in the number exhibiting abnormal uterine discharges. PMID- 2219642 TI - Antibiotic residue in milk. PMID- 2219641 TI - Delayed drainage of neomycin from the uterus of mares susceptible to endometritis. PMID- 2219644 TI - Tail docking. PMID- 2219643 TI - Professions under attack. PMID- 2219645 TI - Welfare of exported livestock. PMID- 2219646 TI - Drastic measures. PMID- 2219648 TI - Efficacy of a baiting system for vaccinating foxes against rabies with vaccinia rabies recombinant virus. AB - The efficacy of a vaccinia-rabies recombinant virus (10(8) TCID50) contained in a machine-made baiting system has been tested in 22 captive young foxes which were divided into three experimental groups of six and a control group of four foxes. Each fox in groups 1, 2 and 3 were fed one, two and three vaccine-baits, respectively, on successive days. The four unvaccinated foxes were housed separately. As shown by the incorporation of a tetracycline biomarker into their bones, all the baited foxes ingested at least one bait. Thirty days after baiting seroconversion to rabies was observed in 15 (83 per cent) of the foxes and seroconversion to vaccinia in 14 (78 per cent). Sixteen of the 18 (89 per cent) baited foxes resisted a rabies challenge 30 days after baiting. One cub was protected against rabies despite the absence of detectable anti-rabies antibody. The results demonstrate that the bait-sachet system permits a good release of the virus suspension into the mouth. PMID- 2219647 TI - Analysis of peritoneal fluid as a diagnostic aid in grass sickness (equine dysautonomia). AB - The analysis of peritoneal fluid is of value in the differential diagnosis of equine colic but its characteristics have not been evaluated in grass sickness. Peritoneal fluid was collected from 15 normal horses and from 11 cases of medical colic, 11 cases of surgical colic, 20 cases of acute grass sickness and 13 cases of subacute grass sickness. The fluid was analysed for its appearance, total and differential white cell count, specific gravity, total protein concentration and total and intestinal alkaline phosphatase activity. Fluid from cases of medical colic was normal in these respects. Surgical cases were unique in having bloodstained fluid with a high alkaline phosphatase activity. Grass sickness cases had a higher specific gravity and protein content than the cases of medical colic although the appearance of the fluid was similar. Grass sickness cases were distinguishable from cases of surgical colic on the basis of the appearance of the fluid and its lower alkaline phosphatase activity. PMID- 2219649 TI - Detection of antibody to Salmonella enteritidis by a gm flagellin-based ELISA. PMID- 2219650 TI - Comparison of a dot-ELISA and a plate-ELISA for bovine brucellosis diagnosis. PMID- 2219651 TI - Dystocia in Friesian heifers. PMID- 2219652 TI - Role of veterinary nurses. PMID- 2219653 TI - Summer mastitis caused by Pasteurella haemolytica biotype A. PMID- 2219654 TI - Treatment of obese dogs. PMID- 2219655 TI - A comparative study on irritation and residue aspects of five oxytetracycline formulations administered intramuscularly to calves, pigs and sheep. AB - After intramuscular (IM) administration (dose 20 mg/kg) of three 20% (Terramycin/LA (product A), Alamycin LA (product B) and Terralon 20% LA (product C) and two 10% oxytetracycline (OTC) formulations (Engemycin 10% (product D) and Oxyject 10% (product E)), to calves, pigs and sheep, the OTC residue concentrations were determined in organs, muscle, fat, plasma, urine and at the injection sites at 10 days post injection (p.i.). At that time the irritation at the injection site was studied, too. The three 20%-formulations (products A, B, C) and one 10%-formulation (product E) induced considerable local irritation in and between the muscles. This was most pronounced in calves and pigs; in sheep the extent of irritation was limited. Ten days after administration of formulations A, B, C and E, OTC residues were found in organs and the OTC recovery at the injection sites varied widely among the three species. Following IM injection of product D minimal tissue irritation and no OTC residues could be detected at the injection site at 10 days p.i. The differences in local tissue irritation and the residue state of the carcass (including injection site) are related to the various solvent systems used in the formulations. PMID- 2219657 TI - Three arterial ostia in the base of the pig's heart. Abnormal ductus arteriosus or an additional stem vessel? AB - A macroscopic description of four hearts showing three arterial ostia in the base of the pig's heart was carried out. Portions of the vascular walls were histologically examined in three hearts. All hearts belong to the Tetralogy of Fallot group. Spitzer's hypothesis concerning the phylogenetic development of the mammalian heart was tested against the observations. The hypothesis could not be verified. The study leads to the conclusion that the ductus arteriosus has its origin in the base of the heart in the four hearts studied. PMID- 2219656 TI - Haematology and blood-chemistry for predicting abscesses and other abnormalities in slaughtered pigs. AB - Blood values of slaughtered pigs were determined in an attempt to relate the blood profile with the prevalence of abscesses. To this end 319 pigs were selected and grouped into classes on the basis of pathological ante- and post mortem findings. The classes thus distinguished were (i) no pathology, (ii) pleurisy or pneumonia and (iii) abscesses occurring singly, metastasised or in combination with other abnormalities. By stepwise discriminant analysis it was established that the blood variables ln(fibrinogen) and albumin were particularly suitable for the detection of abscesses in slaughtered pigs. In this way a correct classification of 89.3% of affected pigs is possible. The numbers of false-positives and false-negatives were 19.3% and 10.7%, respectively. For meat inspection purposes application of blood analyses is promising. For application in meat-inspection practice rapid on-line methods need to be devised. PMID- 2219658 TI - Survival time in dogs with spontaneous atrial fibrillation related to scintigraphically measured cardiac performance. AB - In 40 canine patients with spontaneous atrial fibrillation (AF) cardiac performance was measured scintigraphically and correlated with the survival time (ST) following the diagnosis of AF. The parameters used for cardiac performance were heart rate (HR), end-diastolic left ventricular volume (EDV), ejection fraction of the left ventricle (EF), left ventricular regurgitation fraction (RF) and cardiac output (CO). ST varied from 3 days to 780 days. Two groups of animals were distinguished as previously described: group A (EF less than 0.3, n = 26) and group B (EF greater than or equal to 0.3, n = 14). The median ST (90 days) in group A was only weakly significant (p = 0.1) shorter than in group B (150 days). RF was significantly lower in group A than in group B (p less than 0.001). A weak correlation was found between ST and EF (r = 0.28; p = 0.04). It was concluded that the prognosis in the described AF patients is slightly favourable if EF is normal or only moderately reduced. PMID- 2219659 TI - Pharmacokinetics of chloramphenicol in sheep after intravenous, intramuscular and subcutaneous administration. AB - The pharmacokinetics of chloramphenicol were studied in sheep after 3 single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administrations (30 mg/kg). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After IV and SC administrations, the plasma-concentration time graphs were characteristic of a two-compartment model, and after IM administration it was characteristic of a monocompartment model. The two routes of absorption were not bioequivalent. Using the kinetic values, multidose regimens to maintain the therapeutic chloramphenicol blood level (5 micrograms/ml) were proposed: 60 mg/kg every 12 hours for 72 hours for the IM administration and 45 mg/kg administered subcutaneously according to the same regimen. A study of the chloramphenicol residues in tissues was carried out. Chloramphenicol residues remained at the injection site, and 400 hours would be necessary to obtain the level of 10 micrograms/kg. Determination of the creatinine phosphokinase serum values showed that the subcutaneous route induced less damage to muscle than the intramuscular route. PMID- 2219660 TI - Efficacy of toltrazuril in broilers and development of a laboratory model for sensitivity testing of Eimeria field isolates. AB - (1) The efficacy of toltrazuril (Baycox) against coccidiosis was established on a broiler farm in an intermittent application during five consecutive growing periods. Treated birds were fed a broiler ration without anticoccidials. The efficacy of Baycox was compared with the nicarbazin-salinomycin shuttle. It was concluded that Baycox retarded the onset of Eimeria infection for several weeks. During the fifth rearing period coccidiosis problems emerged on the farm in all birds during medication, suggesting development of resistance. (2) During a laboratory experiment the efficacy of Baycox was studied in birds after inoculation with different numbers of oocysts at 7, 10 or 15 days of age. Baycox was applied at 10 and 11 days of age. In all cases medication with Baycox protected birds from coccidiosis during a period of at least 7 days. This effect of Baycox could be due to the long-existing tissue levels of the product and its metabolites as well as its specific effect on the second generation of schizonts. (3) In another laboratory experiment coccidia obtained from field trials were tested for sensitivity to Baycox in conjunction with two strains obtained from farms were coccidiosis emerged during application. The inoculation model developed in this study was used for sensitivity testing. One of the Eimeria strains tested was resistant to the product, one strain was tolerant and the remaining two strains, including the control strain, were fully sensitive to Baycox. PMID- 2219661 TI - Characterisation of Chlamydia psittaci isolated from a horse. AB - This paper describes the isolation and characterisation of a strain of Chlamydia psittaci obtained from a nasal swab taken from a horse with serous nasal discharge. Initial isolation was achieved in cycloheximide-treated McCoy cell monolayers. Chlamydial inclusions stained by immunofluorescence either with a rabbit antiserum raised against C. psittaci or with a monoclonal antibody directed against the genus-specific lipopolysaccharide antigen were single and compact. They did not stain with iodine or with a monoclonal antibody reactive against Chlamydia trachomatis. The agent was re-isolated in the yolk sacs of embryonated hens eggs and designated N16. Identification of the agent was confirmed by electron microscopy. Unique plasmid DNA was prepared from a purified suspension of chlamydial elementary bodies (EBs), and analysed by electrophoresis through 1.0% agarose gels stained by ethidium bromide. This strain of C. psittaci grew relatively slowly in cycloheximide-treated McCoy cells, and the yield of elementary bodies during the course of one growth cycle was relatively low. PMID- 2219662 TI - Efficacy against ovine enzootic abortion of an experimental vaccine containing purified elementary bodies of Chlamydia psittaci. AB - A vaccine prepared from purified, inactivated elementary bodies of Chlamydia psittaci protected sheep against abortion after subcutaneous challenge with live chlamydiae. Immunoblot analysis of serum samples revealed a consistently dominant antibody response against the chlamydial major outer membrane protein in all vaccinated sheep. Reactions to other chlamydial antigens were also detected but were less pronounced or inconsistent. Serological responses detected by complement fixation were variable and did not correlate with immunity. PMID- 2219663 TI - Biochemical and immunochemical characterisation of strains of Treponema hyodysenteriae. AB - The protein composition of 18 clinical isolates of Treponema hyodysenteriae from pigs with swine dysentery in Australia were compared by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot analysis. Coomassie Blue stained SDS-PAGE-profiles of whole cell and outer membrane (OM) proteins demonstrated the same gel pattern among the T. hyodysenteriae isolates, particularly the OM proteins in the molecular mass (Mr) range of 30 kDa to 40 kDa. The T. hyodysenteriae isolates were categorised into two distinct groups (A and B) based on the strain-variability in the 37 kDa OM protein. Immunoblotting of whole cell proteins after SDS-PAGE using serum from rabbits and pigs immunised with known T. hyodysenteriae serotypes revealed a number of common immunoreactive bands in all isolates. LPS typing of the T. hyodysenteriae isolates by immunoblotting with the rabbit antiserum revealed one additional serotype emphasising the LPS heterogeneity among the strains isolated from geographic locations in Australia, Great Britain and the U.S.A. Immunoblotting of the OM preparations revealed several common immunoreactive polypeptides corresponding to Mr values of 34 kDa to 30 kDa among the T. hyodysenteriae and T. innocens isolates but a distinct 39 kDa found only in the T. hyodysenteriae isolates. Trypsin proteolysis of intact. T. hyodysenteriae cells caused selective loss of these and other major abundant proteins identifying the location of the 39 kDa, 36 kDa, 34 kDa and 30 kDa proteins on the cell surface and suggesting a possible role of these proteins in the pathogenesis of swine dysentery. PMID- 2219664 TI - Factors influencing the degree of in vitro bacterial adhesion to ovine mammary gland epithelial cells. AB - Bacterial adhesion to mammary gland epithelial cells (EC) may play a role in the pathogenesis of mastitis. In vitro adherence systems have been developed to study mastitis in cattle but little has been done in sheep. In this work, a method is described for obtaining mammary gland cell preparations containing greater than or equal to 65% EC from live or dead ewes, using a Ficoll-Hypaque flotation method (cell viability = 70-90%). An in vitro adhesion assay procedure was also developed to study the interaction between EC and ovine mastitis bacterial strains. It was observed that, under the test conditions, adherence increased as the incubation time was prolonged from 30 to 120 min (P less than 0.05). Adhesion was greater at incubation temperature of 37 degrees C than at 22 degrees C (P less than 0.001). An acidic pH (5.9) was associated with an increase in adhesion, when compared with a higher pH (7.2; P less than 0.05). Tween 20, Tween 80 and bovine serum albumin helped to eliminate a background of unbound bacteria from the test slides, but they also inhibited adhesion to some strains. Strain differences in adhesion and in ability to form a background were also observed. Some of these findings may have in vivo implications. PMID- 2219665 TI - Bactericidal activity in the sera of mice vaccinated with Pasteurella multocida type A. AB - The susceptibility of Pasteurella multocida to killing by serum and the ability of protective vaccines to stimulate this mechanism of immunity in mice were investigated. P. multocida type of bovine origin was used to prepare a vaccine incorporating heat killed organisms and for homologous infection of mice. Bactericidal capacity and ELISA antibody titres were determined for individual mouse sera. Protection was clearly associated with bactericidal antibodies raised by vaccination. The bactericidal assay may be useful as a rapid, simple screening test of vaccinated mice for functional protective antibody levels. PMID- 2219666 TI - Susceptibility of Mongolian gerbils (Meriones unguiculatus) to leptospires and the protective effect of vaccination. AB - Mongolian gerbils, Meriones unguiculatus, were shown to be highly susceptible to Leptospira interrogans serovars such as icterohaemorrhagiae, copenhageni, canicola, autumnalis, javanica, pyrogenes and hebdomadis as compared to guinea pigs and hamsters. Mortality with signs of haemorrhage and jaundice was recorded in all experimental rodents after intraperitoneal inoculation with all strains of the serovars indicated. However, Mongolian gerbils were comparatively susceptible to strains which were of low virulence to guinea pigs and hamsters. Use of leptospiral vaccination proved effective in protecting the animals against inoculum challenges. The Mongolian gerbil is a species that may be selectively and preferentially useful for assays on the protective effects of leptospiral vaccination. PMID- 2219667 TI - Diagnosis of bovine brucellosis by enzyme immunoassay of milk. AB - Enzyme-immunoassays using lipopolysaccharide as antigen were developed for the detection of bovine IgG1, IgG2 or IgA Brucella antibodies (Ab) in milk. The results of these tests were compared with those of the milk ring test (MRT) by analyzing 3212 bulk milk samples from farms located in regions where brucellosis is prevalent. Among the 105 herds detected by ELISA and/or MRT, 29 infected herds were detected by ELISA only. The 40 MRT-positive herds were also ELISA positive. Five herds became infected during the study and were detected by ELISA 15 days to 6 months prior to detection by MRT. The ELISA IgG1 titration (IgG1 ELISA) detected 92.8% of the herds found positive in the three ELISA assays. The concomitant use of IgA ELISA raised the sensitivity to 100% but slightly decreased the specificity. The IgG2 ELISA did not improve the diagnosis. The sensitivity of MRT and IgG1 ELISA was compared by testing successive dilutions in negative milk of 110 individual MRT positive milks samples. On average, IgG1 ELISA was 22 times more sensitive than MRT. PMID- 2219668 TI - Characteristics of the Shiga-like toxin produced by Escherichia coli associated with porcine edema disease. AB - Shiga-like toxin (SLT-IIv) from Escherichia coli strains associated with edema disease of pigs was characterized and compared with SLT-I, SLT-II, and the SLT of E. coli strain HI8 (SLT-HI8). SLT-IIv from an E. coli K12 in which the genes for SLT-IIv had been cloned was indistinguishable from SLT-IIv of wild strains of E. coli from edema disease. There was cross-neutralization among all SLTs except SLT I. The different SLTs could be distinguished by heat lability, with the descending order of heat lability being SLT-IIv, SLT-II, SLT-I, and SLT-HI8. SLT IIv and SLT-HI8 had lower cytotoxic titers on HeLa cells compared with Vero cells and were more active on MDBK cells than were the other SLTs. All SLTs were enterotoxic in rabbit but not in pig intestine and SLT-IIv was less enterotoxic than SLT-I. SLT-IIv had a lower LD50 in mice than did the other SLTs. PMID- 2219669 TI - A symmetric axis-based method for measuring the projected femoral angle of inclination in dogs. AB - A new, simple and more consistent method for measuring the projected angle of inclination of the canine femoral neck was devised and tested. This method, based on the principles of symmetric axis (symax) shape analysis, was compared with three other techniques currently in use. Diplomates of the ACVR or ACVS and senior veterinary students were asked to perform measurements of the angle of inclination using the four methods, record their results, and answer several questions about the techniques. Although greater precision was not evident when performed by diplomates, descriptive statistics and a significant difference among the student-derived variances of the four methods demonstrated that the symax-based measurements were most consistent. PMID- 2219670 TI - Partial carpal arthrodesis for third degree carpal sprains. A review of 45 carpi. AB - The efficacy of partial carpal arthrodesis was evaluated retrospectively in 39 dogs (45 carpi) with severe sprains of the middle carpal joints, the carpometacarpal joints, or both. The carpometacarpal joint was the most frequently injured joint. Jumping or falling from heights was the cause of injury in 49% of these animals. Of the 25 owners who responded to a mailed questionnaire (mean follow-up, 32 months), all stated their animal had improved or greatly improved after partial carpal arthrodesis and all were pleased or very pleased with the final surgical result. Hyperextension persisted in 11% of the cases and degenerative joint disease of the antebrachiocarpal joint was present in 15.5% of the cases. No dogs with partial carpal arthrodesis required panarthrodesis at a later date. PMID- 2219671 TI - The effects of aortic occlusion on transcranially induced evoked potentials in the dog. AB - Evoked potentials were produced by anodal stimulation over the motor cortex in six dogs. Potentials were recovered from the cranial thoracic and caudal lumbar portions of the spinal cord, and the radial and sciatic nerves. Evoked potential averages were recorded every 1.5 minutes during 40 minutes of aortic occlusion and during 40 minutes of reperfusion. Mean amplitudes of evoked potentials recovered from the caudal lumbar spinal cord decreased to 50% of original values at minute 12.2. Upon release of occlusion, the evoked potentials returned to baseline levels and remained there throughout the period of reperfusion. Sciatic nerve amplitudes decreased to 50% of original values at minute 4.5. In no subject could wave forms be recovered after minute 9.0. Upon release of occlusion, the evoked potentials returned to baseline levels and above, then deteriorated to 29 +/- 12% after 40 minutes of reperfusion. We concluded that transcranially induced evoked potentials were highly sensitive to spinal cord ischemia. Evoked potentials recovered from the sciatic nerve were consistent with functional grey matter immediately upon reperfusion, but deteriorated during reperfusion. PMID- 2219673 TI - Transendoscopic Nd:YAG laser surgery for treatment of epiglottal entrapment and dorsal displacement of the soft palate in the horse. AB - Transendoscopic neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was used to treat 12 standing horses with epiglottic entrapment (EE) or dorsal displacement of the soft palate (DDSP), or both. In four horses, transendoscopic laser staphylectomy was performed. The most common presenting complaints were respiratory stridor, cough, and exercise intolerance. Ten horses with EE healed without epiglottic complications; in one horse, partial adhesion of the aryepiglottic fold to one side of the epiglottis was corrected surgically through a laryngotomy incision. One horse with DDSP had no further signs, one continued to have continual DDSP, and two had induced DDSP. Transendoscopic Nd:YAG laser proved to be a feasible means of correcting EE and selected cases of DDSP. PMID- 2219672 TI - Subtotal canine prostatectomy with the neodymium: yttrium-aluminum-garnet laser. AB - A technique was developed for subtotal prostatectomy in dogs with the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. In six normal dogs, full thickness necrosis of the prostate occurred if the central-lateral region within 5 mm of the urethra was photoablated at 60 watts for 1 second. Moderate to superficial necrosis occurred when the prostate within 5 mm of the urethra was photoablated at 35 watts for 2 seconds or 60 watts for 0.5 second. At necropsy, leakage of the urethra occurred in two dogs at sites treated at 60 watts for 1 second. In a clinical study, complications associated with subtotal prostatectomy with the Nd:YAG laser (n = 6) were compared with complications associated with prostatic drainage (n = 6) in dogs with prostatic disease. Intraoperative death (2/6 dogs) and nocturnal incontinence (4/4 surviving dogs) occurred with subtotal prostatectomy. Uncontrolled prostatic infection (2/6 dogs) occurred with prostatic drainage and resulted in the death of one dog on day 11. Four of five dogs surviving prostatic drainage developed recurrent urinary tract infection. PMID- 2219674 TI - Arytenoidectomy for advanced unilateral chondropathy with accompanying lesions. AB - A noncurrent prospective study of nonworking horses with arytenoid chondropathy was conducted to confirm a clinical impression that horses with unilateral chondropathy and accompanying lesions had a poorer prognosis after arytenoidectomy than horses with bilateral or uncomplicated unilateral chondropathy. Surgical failure was defined as death, euthanasia, permanent tracheostomy, or reoperation. Survival to surgical failure and clinical improvement data were compared between horses with and without accompanying lesions treated by arytenoidectomy. The probability of surgical failure was significantly higher and times to surgical failure were significantly shorter for horses with unilateral chondropathy and accompanying lesions than for horses with bilateral or uncomplicated unilateral chondropathy. Clinical improvement at the median follow-up time of 6 months was significantly less likely in horses with than without accompanying lesions. Horses with endoscopic evidence of inflammation and paralyzed opposite cartilage were significantly less likely to improve clinically than horses with pharyngeal cicatrix. PMID- 2219676 TI - Intra-articular replacement of bovine cranial cruciate ligaments with an autogenous fascial graft. AB - Transected cranial cruciate ligaments in nine Holstein heifers were replaced with an autograft harvested from fascia on the medial surface of the gluteobiceps muscle and a connected segment of the lateral patellar ligament. There was minimal lameness at month 1, and all animals were sound by month 2. There was no evidence of degenerative joint disease in any stifles examined at necropsy on days 90, 120, or 365. Augmented healing of the severed cranial cruciate ligaments occurred in several animals. The mean failure strength of the cranial cruciate ligament replacements was 29.7% of the failure strength of the contralateral normal cranial cruciate ligament in four heifers. The technique was successful in eight of 13 bulls and cows with ruptured cranial cruciate ligaments. Animals treated successfully had significantly lower body weights than those with unsuccessful outcomes. PMID- 2219675 TI - The etiology and surgical management of tracheal collapse in calves. AB - The mean ages of 10 calves with tracheal collapse were 2.7 weeks at onset of clinical signs and 9.4 weeks at presentation for treatment. Inspiratory and expiratory dyspnea and stunted growth were the most common clinical signs. There were abnormalities of the cranial ribs consistent with healing fractures with redundant callus in eight lateral thoracic radiographs. Tracheal collapse in calves may result from cranial thoracic trauma during or soon after birth. Short polypropylene ring prostheses made from 60 ml syringe barrels were placed on the tracheas of four calves with cervical tracheal collapse. There were cranial rib masses in all calves and resection of the right first and second ribs was necessary in one calf to allow placement of prostheses. Dyspnea was relieved in all calves. One calf died of unrelated causes in year 3, and one calf had recurrence of clinical signs at month 5 and was euthanatized. In both calves, tracheal stenosis resulted from continued growth and infolding of the trachea within the constraints of the prostheses. One calf was alive at month 11, and one calf died of acute bronchopneumonia on day 2. Removal of tracheal prostheses in calves is recommended after 2 to 3 months if clinical signs recur. PMID- 2219677 TI - Equine post-anesthetic lameness. A retrospective study. AB - The incidence of post-anesthetic lameness in 655 horses undergoing 733 anesthetic episodes over a 3 year period was 6.4%. Nineteen factors previously reported or proposed to play a role in the development of post-anesthetic lameness were evaluated statistically. Only hypotension and the duration of the anesthetic period were significant factors. PMID- 2219678 TI - Reversal of oxymorphone sedation by naloxone, nalmefene, and butorphanol. AB - The effects of naloxone (0.4 mg and 1.2 mg intravenously [IV]), nalmefene (0.03 mg/kg IV) and butorphanol (0.2 mg/kg IV and 0.4 mg/kg IV) on oxymorphone-induced sedation were studied in six dogs over a 4-hour observation period. The same dogs were observed for 4 hours untreated (unsedated control) and with oxymorphone sedation followed by saline solution (sedated control). The reversal drug or saline placebo was administered IV 20 minutes after oxymorphone (4.5 mg IV). Blinded observers evaluated the dogs for positional and attitudinal responses, heart rate, and respiratory rate. Sedated dogs treated with nalmefene most closely resembled unsedated dogs in all observed variables. Naloxone was most effective when administered at the higher dose. Mild renarcotization occurred in two dogs at hour 2, even after the higher naloxone dose. Residual sedation was observed in all dogs treated with 0.4 mg naloxone. Butorphanol resulted in partial reversal of sedation at both dosage levels. However, the degree of sedation was significantly less than that observed in the saline-treated controls, and it appeared that 0.4 mg/kg butorphanol may be clinically useful for opiate reversal in some situations. PMID- 2219679 TI - [A complex x-ray study of patients with enterocutaneous fistulas]. AB - The paper is concerned with analysis of the results of x-ray examination of 78 patients with enterocutaneous fistulas of various etiology and site. The authors have shown the characteristic features of x-ray examination of patients in whom the fistulas were at the acute phase of their development. They have also defined the diagnostic value of the employed methods and their efficacy for the diagnosis not only of fistulas but also of related complications (inflammatory infiltrates and abscesses of the abdominal cavity, fatty phlegmon, purulent "fillings", complicated fistulas, etc.). During combined x-ray investigation accurate diagnosis of fistulas was established in 97.4% of the patients, purulent complications were revealed in 94.6%. PMID- 2219680 TI - [X-ray diagnosis of primary sclerosing cholangitis]. AB - Primary sclerosing cholangitis (PSC) should be regarded as a disease of the bile tracts which is difficult to diagnose rather than a rare disease. Combined radiodiagnostic investigation in the preoperative period is of great importance. Direct methods of an induced contrast study of the biliferous system (transcutaneous transhepatic cholangiography, endoscopic retrograde pancreatocholangiography) play a major role in the diagnosis of PSC. The authors present 11 cases, describing in detail x-ray semiotics of various sites of PSC and its differential diagnosis with similar diseases. PMID- 2219681 TI - [The state of the veins of the esophagus and the stomach in chronic diffuse liver diseases (based on data from a combined roentgeno-endoscopic and echographic study)]. AB - Combined roentgenological and endoscopic investigation was used to study the state of the esophageal submucous veins. Echography was used for investigation of the gastric subserous veins and esophageal abdominal veins. The results obtained indicate that in the presence of portal hypertension there are two types of shunting: via the esophageal submucous (82%) and subserous (18%) veins. In patients with the predominant affection of the esophageal subserous veins x-ray investigation and endoscopy do not allow correct estimation of the presence and a degree of the gastroesophageal shunt. Echography results enable one to arrive at a correct conclusion in all patients. PMID- 2219683 TI - [Differential ultrasonic diagnosis of jaundice]. AB - Multiprojection ultrasound investigation was performed in 87 patients with jaundice. Echography was shown to be an effective method of differential diagnosis of parenchymatous and obstructive jaundice. The accuracy of ultrasound introscopy in the detection of parenchymatous jaundice was 84.3%, that in the detection of mechanical jaundice was 100% (the general accuracy being 85.7%). The authors proposed an algorithm for the use of ultrasound tomography, x-ray and clinico-instrumental methods in differential diagnosis of jaundice of different etiology. PMID- 2219682 TI - [Embolization of the hepatic artery in cases of atypical anatomical structural variants in patients with malignant liver tumors]. AB - Therapeutic embolization of the hepatic artery was performed in 60 patients with nonresectable malignant liver tumors. Atypical topographical anatomical variants of the arterial system of the liver were revealed in 10 of them (16.7%). In 8 patients two hepatic vessels, one coming out of the celiac artery, the other--out of the upper mesenterial or left gastric artery supplied a tumor with blood. In three of them one vessel was embolized, in five patients both arteries were embolized. The blocking of the entire blood flow of a tumor brought about a positive clinical effect in all the patients. Embolization of one blood-supplying artery alone led to no improvement. A conclusion was made of a necessity to achieve arterial devascularization of the entire tumor tissue area during intravascular therapy. PMID- 2219684 TI - [Ultrasonic diagnosis of liver hydatidosis]. AB - The paper is concerned with a study of an ultrasound picture of verified hydatidosis in 62 patients. The symptoms of hydatid cysts are the presence of daughter cysts and "hydatid sand", cuticular membrane desquamation, local cyst wall thickening and parietal layers, a necrotic zone in a preparasitic space and cyst calcification. The detection of these symptoms helps to estimate not only the type of a hydatid cyst but also the state and character of parasite activity permitting a choice of therapeutic tactics. PMID- 2219685 TI - [Computed tomography in the diagnosis of diffuse diseases of the liver]. AB - Methods of CT, echotomography and scintigraphy of the liver were used to investigate 95 patients with diffuse liver diseases (fatty dystrophy, hepatitis, cirrhosis, hemosiderosis and amyloidosis). CT changes in these diseases were described. A high efficacy of CT was established in the detection of diffuse liver lesions and portal hypertension permitting one to give up in some cases invasive puncture biopsy of the organ. PMID- 2219686 TI - [Magnetic resonance tomography, computed tomography and ultrasonic diagnosis of hemangiomas of the liver]. AB - The paper is concerned with the potentialities of modern radiation methods in the diagnosis of liver hemangiomas. USI, CT, angiography and MR-tomography (MRT) were used for investigation of 64 patients with liver hemangiomas. The diagnostic potentialities and the role of each of the above methods in the diagnostic algorithm in liver hemangiomas were studied. The results of the investigation have shown that MRT possesses a higher informative value than USI and CT in the diagnosis of liver hemangiomas and can even replace angiography in the verification of diagnosis. PMID- 2219687 TI - [X-ray diagnosis of peptic ulcers of the jejunum]. AB - The paper is devoted to a study of the results of clinicoroentgenological and endoscopic investigation of 188 patients aged 23 to 60 who developed jejunal peptic ulcer. It was done to specify the features of an x-ray picture of jejunal peptic ulcers with relation to the cause of ulcer development and optimum methods of x-ray investigation. The predominant localization of peptic ulcer in the jejunal efferent loop and its typical ulcero-cicatricial deformity were established. Jejunal peptic ulcers developing as a result of an insufficient area of resection, are characterized by a relatively benign course of the disease. In case ulcer development was determined by the residual antral stomach mucosa at the duodenal stump or by the Zollinger-Ellison syndrome, considerable pathological changes (gigantic ulcer sizes greater than 2.5 cm and a sharp deformity of the jejunal efferent loop) were noted. PMID- 2219688 TI - [The sequence of interventions in pancreatic cavities]. AB - Schemes for the sequence of therapeutic interventions were worked out based on experience in the recognition of 56 pancreatic cavitations (cysts, abscesses), US assisted diagnostic punctures, 28 external drainages of the cavities (mainly prolonged catheterization), 4 diagnostic and therapeutic transcutaneous wirsungographies. The authors also worked out recommendations for a choice of instruments for prolonged external transcutaneous drainage of pancreatic cysts and abscesses, cleansing of the cavity and its sclerosing, inoperative cystogastrostomy between a cyst and a stomach stent. PMID- 2219690 TI - [Stage I cancer of the stomach (T1N0M0P1-2). Classification and x-ray diagnosis (review of the literature]. PMID- 2219689 TI - [Magnetic resonance tomography in focal diseases of the liver (review)]. AB - A review is devoted to the use of MR-tomography in the diagnosis of focal liver lesions. Various pulse sequences and a choice of an optimum variant are under discussion. A possibility of contrast intensification of MR-tomograms with paramagnetic substances is indicated, the problems of occurrence of motor artefacts are considered. A conclusion has been made that relaxation time can serve a tissue characteristic, permitting differential diagnosis on the basis of difference in relaxation time between different types of pathological changes. PMID- 2219691 TI - [X-ray diagnosis of the spread of cancer of the esophagus to the trachea and major bronchi]. AB - X-ray and endoscopic investigations were compared in 80 operated on patients to estimate the role of the x-ray method for a choice of adequate therapeutic tactics for esophageal cancer patients. Operations were explorative or palliative resulting from the involvement of the tracheobronchial tree in a tumor process. The efficacy of the x-ray method in the detection of tracheal compression by an esophageal tumor is higher than that of tracheobronchoscopy which in its turn, has its advantages in the determination of tumor spreading to the left major bronchus. PMID- 2219692 TI - [Methodologic procedures in the study of the biliary system using cholecystography]. AB - New methods of x-ray investigation of the biliary system (BS) were proposed. A method of hydrostatic load in per os cholecystography, a method of the combined use of per os and iv cholecysto-cholangiography with hydrostatic load, and the use of finely divided suspension are simple and reliable, permitting one to obtain objective information on the BS. PMID- 2219693 TI - [Indirect sialadenolymphography of the major salivary glands]. PMID- 2219694 TI - [Duodenography in hypotension using sound waves]. PMID- 2219695 TI - [Standard serial cholecystography in the diagnosis of digestive disorders following gastrectomy]. PMID- 2219696 TI - [Stenosis of the pylorus in adults (x-ray endoscopic studies)]. PMID- 2219697 TI - [A.S. Popov--one of the founders of Soviet roentgenology]. PMID- 2219698 TI - Primary structure and post-translational processing of the Berne virus peplomer protein. AB - The nucleotide sequence of the peplomer (P) protein gene of Berne virus (BEV), the torovirus prototype, was determined. The gene encodes an apoprotein of 1581 amino acids with an Mr of about 178K. The open reading frame was cloned behind the T7 RNA polymerase promoter and its translation product was identified as the BEV P protein precursor by in vivo expression and immunoprecipitation. The deduced amino acid sequence contains a number of domains which are typical for type I membrane glycoproteins: an N-terminal signal sequence, a putative C terminal transmembrane anchor, and a cytoplasmic tail. Eighteen potential N glycosylation sites, two heptad repeat domains, and a possible "trypsin-like" cleavage site were identified. The mature P protein consists of two subunits and their electrophoretic mobility upon endoglycosidase F treatment strongly suggests that the predicted cleavage site is functional in vivo. The heptad repeat domains are probably involved in the generation of an intra-chain coiled-coil secondary structure; similar inter-chain interactions can play a role in P protein oligomerization. Using a sucrose gradient assay the P protein was indeed shown to form dimers. The intra- and inter-chain coiled-coil interactions may stabilize the elongated BEV peplomers. PMID- 2219699 TI - Purified phi 6 nucleocapsids are capable of productive infection of host cells with partially disrupted outer membranes. AB - Purified nucleocapsids of bacteriophage phi 6, lacking the phage lipid envelope, are unable to infect intact Pseudomonas syringae host cells. A method for studying the process by which a naked virus particle, the phi 6 nucleocapsid, penetrates the host cytoplasmic membrane was developed. Host cells were rendered competent for nucleocapsid infection by treatment with repeated washings with salt and sucrose and the subsequent addition of lysozyme. This treatment disrupts the outer membrane, permitting the nucleocapsid to reach the cytoplasmic membrane and to infect the cell. The nucleocapsid infection is blocked by monoclonal antibodies raised against the nucleocapsid shell protein P8. PMID- 2219700 TI - Sequence conservation and divergence of hepatitis delta virus RNA. AB - The complete RNA sequence of the hepatitis delta virus (HDV) obtained from the Nauru Island in the Pacific was determined by cDNA cloning and amplification by polymerase chain reaction (PCR). The sequence showed 14-17% divergence from the two known HDV RNA sequences. There are three highly conserved domains: the region around the autocatalytic cleavage site of the genomic RNA (nucleotides 659 to 772), the region around the autocatalytic cleavage site of the antigenomic-sense RNA (nucleotides 847 to 966), and the region around the middle one-third domain of the open reading frame (ORF) encoding the hepatitis delta antigen on the antigenomic RNA (nucleotides 1267 to 1347). The two autocatalytic activities are required for the cleavage and ligation of HDV RNA during RNA replication. The third conserved domain codes for the RNA-binding domain of HDAg, which specifically interacts with HDV RNA. Three nucleotide changes within the genomic catalytic sequence are present but did not alter the catalytic cleavage activity of the HDV RNA. Microheterogeneity of the RNA sequences was also detected. One of these occurred within the coding region of the delta antigen, creating an amber termination codon in some of the RNA species. Thus, this HDV strain contains two different RNA species, one of which encodes a delta antigen of 214 amino acids and the other 195 amino acids. These two protein species were detected by immunoblotting of the patient's plasma. In contrast to other HDV strains, only three ORFs capable of encoding more than 100 amino acids each are present in this HDV RNA. We recommend that oligonucleotides complementary to the highly conserved sequences should be used as primers for PCR in clinical detection assays of hepatitis delta virus infection. PMID- 2219701 TI - The vaccinia virus HindIII F fragment: nucleotide sequence of the left 6.2 kb. AB - The nucleotide sequence of the left 6.2 kb of the 13.2-kb HindIII F fragment of vaccinia virus was determined. Translation of the sequence revealed nine closely spaced, tandemly oriented open reading frames (ORFs), all reading leftward. The transcriptional organization of this region was determined by Northern blot and S1 nuclease mapping. The analysis suggested that ORFs 1, 2, 4, 5, 6, 7, and 8 are transcribed early in infection, whereas ORFs 3 and 9 are probably late genes. Two of these ORFs have been reported previously. ORF F4L encodes the small subunit of ribonucleotide reductase and ORF F2L is homologous to a retroviral protease-like gene. PMID- 2219702 TI - Both amino acid changes in nsP1 of Sindbis virusLM21 contribute to and are required for efficient expression of the mutant phenotype. AB - SVLM21 is a mutant of Sindbis virus which in contrast to the standard virus, SVSTD, is able to replicate in Aedes albopictus mosquito cells deprived of methionine. Previously, by making use of the infectious Toto plasmids, we had constructed recombinant viruses containing various SVLM21 sequences, and were thereby able to map the mutations associated with the SVLM21 phenotype to the gene for the nonstructural protein nsP1. Two mutations were found in the nsP1 gene of SVLM21. These led to predicted amino acid changes at residue 87 from Arg to Leu, and at residue 88 from Ser to Cys. In the work presented here, we assess the relative contributions of these two mutations to the SVLM21 phenotype using site-directed mutagenesis to obtain virus encoding only the change to Leu at residue 87 of nsP1 (SVMS319), or only the change to Cys at residue 88 (SVMS321). In addition we show that SVLM10, which was isolated during the selection procedure for SVLM21, encodes only the change at residue 88. In addition to its ability to grow in methionine-deprived mosquito cells, SVLM21 differs from SVSTD in two other respects: (1) it shows an increased sensitivity to neplanocin A (NPA) and (2) it generates increased levels of methyltransferase in infected cells. Whether we looked at resistance to low methionine, sensitivity to NPA, or levels of methyltransferase generated, SVMS319, SVMS321, and SVLM10 all expressed only a partial SVLM21 phenotype. Furthermore we were not able in these experiments to distinguish between these three viruses. We conclude therefore that both amino acid changes, i.e., at residues 87 and 88, are required to produce the full SVLM21 phenotype, and that both changes contribute equally. PMID- 2219703 TI - The nucleotide sequence of abutilon mosaic virus reveals prokaryotic as well as eukaryotic features. AB - The complete nucleotide sequence of abutilon mosaic virus (West Indian isolate, AbMVa) is presented. The resulting genomic structure resembles that of other geminiviruses which are transmitted by the whitefly Bemisia tabaci: AbMV possesses a bipartite circular genome with bidirectional orientation of the open reading frames (ORF). Both components have a common region of 180 bases with 99% homology while the rest of their sequence is distinct. Eukaryotic regulatory transcription elements precede most ORFs and polyadenylation signals are present at the end of most ORFs. However, two ORFs show features of prokaryotic genes. This chimaeric genome organisation is discussed with reference to the finding that AbMV DNA is present in plastids as well as in the nucleus of infected cells. PMID- 2219704 TI - Expression, characterization, and purification of a phosphorylated rabies nucleoprotein synthesized in insect cells by baculovirus vectors. AB - A baculovirus expression vector (AcNPV3) derived from the nuclear polyhedrosis virus of Autographa californica (AcNPV) was prepared containing the complete coding region of the nucleoprotein (N) gene of rabies virus (Gif-sur-Yvette clone of the CVS strain). The gene was placed under the control of the AcNPV polyhedrin promoter and was expressed to high levels (66 mg N protein/liter of 2 x 10(9) cells) by the derived recombinant virus using a Spodoptera frugiperda cell line. Using available antisera, it was established that the antigenic characteristics of the N protein were similar by comparison with those of the native N protein of rabies virus. Characterization of the expressed protein established that, like the N protein of mammalian cell-grown CVS virus, the N protein was phosphorylated. The expressed rabies N protein induced antibodies in mice that reacted strongly with the rabies viral protein. The expressed nucleoprotein was recovered from the insect cells by differential centrifugation followed by ion exchange chromatography. The expressed rabies N protein represents a source of authentic protein suitable for virus diagnosis as well as structural studies. PMID- 2219705 TI - Folding and oligomerization properties of a soluble and secreted form of the paramyxovirus hemagglutinin-neuraminidase glycoprotein. AB - The paramyxovirus SV5 hemagglutinin-neuraminidase (HN) glycoprotein (a type II integral membrane protein) was converted into a soluble and secreted form (HN-F) by replacing the HN signal/anchor domain with a hydrophobic domain that can act as a cleavable signal sequence. Approximately 40% of the HN-F synthesized was secreted from cells (t1/2 approximately 2.5-3 hr). The extracellular HN-F molecules were identified as disulfide-linked dimers and the majority of the population of molecules were resistant to endoglycosidase H digestion. Examination of the oligomeric form of the secreted HN-F, by sucrose density gradient sedimentation, indicated that under conditions where HN was a tetramer, HN-F was found to be a dimer, and no extracellular HN-F monomeric species could be detected. Secreted HN-F was fully reactive with conformation-specific monoclonal antibodies and was enzymatically active as shown by HN-F having neuraminidase activity. Examination of the intracellular HN-F species indicated that HN-F monomers were slowly converted to the disulfide-linked form and that under the sucrose density gradient sedimentation conditions used the HN-F monomers aggregated. Some of the HN-F monomers were degraded intracellularly. These data are discussed in relationship to the seemingly different folding and oligomerization requirements for the intracellular transport of soluble and membrane bound forms of a glycoprotein. The soluble and biologically active form of HN may be suitable for further structural and enzymatic studies. PMID- 2219706 TI - Systemic movement and symptom production following agroinoculation with a single DNA of tomato yellow leaf curl geminivirus (Thailand). AB - Two different DNA species were cloned from purified tomato yellow leaf curl geminivirus particles after annealing a specific primer to virus DNA and generating a second strand; both were approximately 2.8 kbp in length. One clone contains sequences which hybridize to the coat protein gene of tomato golden mosaic virus and most likely represents the A DNA of tomato yellow leaf curl virus (Thailand). The other clone may represent the B DNA of this geminivirus. Both clones contain short sequences which share extensive homology. These sequences have some of the same features of common regions of other geminiviruses. Systemic viral infection of tomato and Nicotiana benthamiana was accomplished by agroinoculation with the proposed A DNA. The symptoms of systemically A-infected plants include stunting, lack of flower production, and mottled, yellowish leaves. At low frequency during agroinoculation of N. benthamiana with a mixture of both DNAs, replication of the second DNA is also detected. In these instances, symptoms are more pronounced than infections where only the A DNA is agroinoculated. This is the first report of a whitefly transmitted dicot-infecting geminivirus capable of infection (via agroinoculation), symptom induction, and systemic movement using a single DNA. PMID- 2219708 TI - Comparative sequence of the helper component (HC) region of potato virus Y and a HC-defective strain, potato virus C. AB - Potato virus C (PVC), a non-aphid transmissible strain of potato virus Y (PVY), was found to code for a protein (PVC-HC) which is similar in molecular weight and immunological reactivity to the helper component protein of PVY (PVY-HC). PVC-HC, however, was inactive with respect to its ability to effect aphid transmission of either PVC or PVY. The 5'-terminal 2.7-kb regions of PVC and PVY were sequenced. Within the HC region there was 92% nucleotide homology between the two strains; comparison of the derived amino acid sequences revealed 24 amino acid differences. Comparison of the PVC-HC sequence with that of five potyviruses revealed 2 amino acid changes which were specific to PVC-HC. These amino acids are prime targets for mutational analysis of HC activity. PMID- 2219709 TI - The hepatitis B virus X-C fusion protein is unlikely to be produced by the mechanism of ribosomal frameshifting. AB - A novel hepatitis B viral (HBV) protein of 35-40 kDa, characterized by antibodies and proposed as an X-C fusion protein, was previously described in core particles isolated from HBV-, WHV-, and GSHV-infected livers. The X and C genes are two adjacent genes in all mammalian hepadnaviruses but are not contiguous in WHV and GSHV. After examination of the X and preC/C junction sequences of 10 HBV, 4 WHV, and 1 GSHV, we found that the ORF of preC can be extended 7 more sense codons upstream so that X overlaps with the preC/C gene in all sequences. The number of overlapping base pairs (bp) is varied: 46 bp in HBV, 19 bp in WHV, and 10 bp in GSHV. In this region a conserved A-track was found to be followed by a pair of inverted repeats, suggesting that a ribosomal frameshift may occur for X-C fusion protein production. To assess this possibility, we have used an in vitro transcription and translation coupling system to identify X-C protein production. Two recombinant SP6 plasmids were used. One contained a full length of the X and preC/C gene of wild-type HBV-DNA and the other fused the X-preC/C gene by inserting a 10-bp HindIII linker at the junction of the X-preC/C region. No X-C fusion protein was detected from the wild-type plasmid. In contrast a large amount of X-C fusion protein was produced from the linker-inserted clone. It appears, therefore, that the X-C fusion protein is unlikely to be produced via the mechanism of ribosomal frameshifting. PMID- 2219707 TI - Does the human immunodeficiency virus Tat trans-activator contain a discrete activation domain? AB - Human immunodeficiency virus type 1 (HIV-1) encodes a transcriptional trans activator, termed Tat, that is absolutely required for viral replication in vitro. By analogy to other known transcription factors, it has been suggested that the HIV-1 Tat protein may contain discrete protein domains that determine sequence specificity and transcriptional activation potential. Here, we report the use of site-directed mutagenesis to examine the functional significance of two candidate activation domains within Tat. A 12 amino acid sequence adjacent to the N-terminus of the Tat protein, which includes a proposed acidic amphipathic alpha-helix activation motif, was found to contribute to, but be dispensable for, Tat function in vivo. In contrast, the integrity of a second potential Tat activation motif, centered on a lysine residue at position 41, was found to be essential for Tat function. However, Tat proteins mutated in this area displayed a fully recessive negative phenotype. Therefore, neither of these two regions of the Tat protein appear to be discrete activation domains. We conclude that previous attempts to categorize Tat as a modular transcription factor have not succeeded and suggest that the functional organization of this complex trans activator remains to be defined. PMID- 2219710 TI - Isolation of a Friend recombinant polytropic virus with a T-cell-restricted leukemogenicity. AB - Hematopoietic malignant cells of various types were isolated from ICFW mice inoculated as newborn or adult with F-MuLV and grafted into recipient mice. After repeated in vivo cell transplants, several recombinant polytropic viruses (also termed MCF or dualtropic viruses) were isolated from tumors by limiting dilution. Two virus isolates designated RA1-17 and EA1-17 were recovered from the spleen and the omentum, respectively, of the same grafted animal. When inoculated into newborn mice, RA1-17 induced erythroblastosis similar to that induced by other Friend recombinant polytropic viruses. Remarkably, EA1-17 induced T-cell leukemia after a short latency. To our knowledge, this is the first description of a polytropic recombinant virus with a T-cell tropism isolated after inoculation of F-MuLV. PMID- 2219712 TI - Vaccinia virus gene D7R encodes a 20,000-dalton subunit of the viral DNA dependent RNA polymerase. AB - The polypeptide encoded by the vaccinia virus open reading frame D7R was synthesized in bacteria. Immunization of rabbits with the polypeptide resulted in antibodies that specifically recognized a virion polypeptide of 20,000 daltons. The immunoreactivity with the 20,000-dalton polypeptide was found to coincide with the virion-associated DNA-dependent RNA polymerase through DEAE-cellulose chromatography and glycerol gradient sedimentation. These results argue that the product of the vaccinia open reading frame D7R is a subunit of the viral RNA polymerase. PMID- 2219711 TI - Systematic classification of HIV biological subtypes on lymphocytes and monocytes/macrophages. AB - The growth properties and cytopathic effects of several HIV-1 and HIV-2 strains were compared between cultures on human lymphocytes and monocytes/macrophages, respectively. For some isolates (among these three paired isolates from blood and cerebrospinal fluid) replication and cytopathogenicity were comparable between lymphocytes and monocytes/macrophages (dual tropic viruses), while others showed a very specific tropism for only one cell type. Yet another subtype grew neither well on lymphocytes nor on macrophages. Taking into account the growth properties in monocytes/macrophages we propose a classification system for HIV subtypes on these cells (alpha-delta), in analogy to the nomenclature for HIV-subtyping on lymphocytes (a-d). Using this system, some prototypic viruses (LAV/HTLV-IIIB, HIV 2ROD, SIVBK28, HIV-2ALT) as well as several other HIV-1 and HIV-2 isolates were subtyped. PMID- 2219713 TI - The complete nucleotide sequence of an infectious clone of porcine parvovirus, strain NADL-2. AB - The complete nucleotide sequence of an infectious clone of porcine parvovirus, strain NADL-2, was determined. The nucleotide sequence organization of the viral genome was found to be similar to that of the other autonomous parvoviruses, such as canine parvovirus and minute virus of mice. PMID- 2219714 TI - Reverse guanine phosphoribosyltransferase selection of recombinant vaccinia viruses. AB - We have developed a procedure for the selection of recombinant vaccinia viruses with applicability to poxvirus mutagenesis studies and to the use of vaccinia virus as an expression vector. The method depends on the specific inability of a recombinant vaccinia virus expressing the Escherichia coli guanine phosphoriboxyltransferase gene (gpt) to form plaques on a hypoxanthine-guanine phosphoribosyltransferase-negative line of mouse fibroblasts in the presence of 6 thioguanine. Recombinant viruses that have the gpt removed can form plaques under selection conditions, thus providing a simple and efficient selection protocol. We have demonstrated the method by isolating a pseudo-wild type revertant virus and a simple deletion mutant virus from a recombinant vaccinia virus with gpt inserted into the vaccinia virus gene encoding the major 35,000-Da secretory protein. PMID- 2219715 TI - Nucleotide sequence and characterization of the 39K gene region of Autographa californica nuclear polyhedrosis virus. AB - The complete nucleotide sequence of the Pstl-K fragment of the Autographa californica nuclear polyhedrosis virus (AcMNPV) genome was determined. This region of the genome contains the delayed early 39K gene and V-ubi, a viral protein with homology to ubiquitine. In addition, Pstl-K potentially encodes five other proteins. Hybrid-select translation mapped nine viral-specific proteins to this fragment. Three proteins were observed with both early and late RNA; two of them comigrated with proteins directed by transcripts made from the 39K open reading frame (ORF). One protein which was only seen with hybrid-selected late RNA comigrated with ubiquitin. A correction of previously published sequence data indicates that there is an additional AUG codon upstream of the 39K ORF. This AUG codon is located 8 nucleotides downstream of the early transcription initiation site. The methionine codon is followed by codons for three amino acids and a termination codon. The 39K ORF is located 102 nucleotides downstream of the minicistron. In vitro transcription-translation experiments confirmed that the downstream AUG serves as the initiation codon for the 39K ORF. Radioimmunoprecipitation experiments indicated that the Pstl-K-encoded 39K protein reacted with antiserum raised against a previously described nuclear matrix-associated 39K protein. PMID- 2219716 TI - Nucleotide sequence and genomic organization of apple chlorotic leaf spot closterovirus. AB - The nucleotide sequence of Apple chlorotic leaf spot closterovirus (ACLSV) genomic RNA has been determined from cDNA clones. It is 7555 nucleotides in length excluding the 3' terminal poly(A) tail and contains three putative open reading frames capable of encoding proteins of 216.5, 50, and 28 kDa. ACLSV RNA has untranslated regions of 151 and 190 nucleotides at its 5' and 3' termini, respectively. The 216.5-kDa ORF encodes a protein which contains the conserved "signature" sequences and has significant homology with the proteins suspected to be involved in viral RNA replication of members of the "Sindbis-like" supergroup of viruses. On the basis of distant homologies with viral movement proteins (M proteins), the 50-kDa ORF is suspected to encode a protein responsible for virus cell-to-cell spread. The 28-kDa ORF contains, in frame, a smaller 21.5-kDa ORF encoding the coat protein of ACLSV. These results show that ACLSV and probably at least the subgroup A of closteroviruses should be regarded as members of the "Sindbis-like" supergroup of RNA viruses. PMID- 2219717 TI - Fiber sequence heterogeneity in subgroup F adenoviruses. AB - The fiber gene of adenovirus type 41 was sequenced and compared to the fiber gene sequence of adenovirus type 40 (A. H. Kidd and M. J. Erasmus, 1989, Virology 172, 134-144), the other known member of subgroup F. The open reading frame, from map units 87 through 92 with transcription from the r-strand, comprised 1686 bases and was 45 bases longer than its counterpart on the Ad40 genome. The 45-base difference appears to have resulted from a block deletion on the Ad40 sequence. Apart from this one region, the Ad40 and Ad41 fiber genes showed remarkably high homology (95.6%), indicating a relatively recent evolutionary divergence. The deduced amino acid sequence of the Ad41 fiber polypeptide was analyzed according to the model of N. M. Green et al. (1983, EMBO J. 2, 1357-1365) for the structure of the adenovirus fiber. Ad41 had one more 15-residue repeat in the shaft region than Ad40, there being 22 repeat motifs. A detailed study of various Ad40 and Ad41 strains with proven genome differences indicated that the 15-amino acid difference in polypeptide length at the 14th repeat motif is a type-specific difference among the subgroup F adenoviruses. However, two uncommon Ad41 strains belonging to 2 of the 16 Ad41 genome types tested had a 15-amino acid block deletion which was different to that of the Ad40 polypeptide. The implication from this work is that the Ad40 fiber gene probably arose from its Ad41 counterpart, but the fiber gene sequences of both types of subgroup F adenovirus are so similar that genetic recombination between strains could occur with some frequency. PMID- 2219719 TI - Characterization of the cord-like structures emerging from the surface of influenza C virus-infected cells. AB - When HMV-II cells (a human malignant melanoma cell line) infected with a newly isolated influenza C strain (Yamagata/1/88) were examined by simple light microscopy, it was found that a large number of cord-like structures which had lengths up to about 500 microns or greater were emerging from the cell surface. The existence of viral glycoproteins (hemagglutinin-esterase, HE) on the surface of these huge structures was confirmed by hemadsorption experiments with erythrocytes from a variety of species as well as by immunofluorescent staining with anti-HE monoclonal antibody. Furthermore, electron microscopy revealed that numerous filamentous particles in the process of budding, each covered with a layer of surface projections approximately 13 nm in length, aggregated with their long axes parallel to form a cord-like structure visible under a light microscope. An electron-dense layer, which presumably consists of membrane protein (M), was seen in cross-sections of all filamentous virions whereas internal nucleocapsids were rarely seen. SDS-polyacrylamide gel electrophoresis of the purified cords also showed that they contained HE and M polypeptides but not nucleoprotein, confirming that long filamentous particles are mostly devoid of nucleocapsids. The emergence of cords on the cell surface was observed in various cell cultures infected with C/Yamagata/1/88 though their number and length varied markedly depending on cell type. The production of cord-like structures was also evident in HMV-II cells infected with any of several different influenza C strains, which suggests that the cord formation is a common feature of influenza C virus group. PMID- 2219718 TI - Expression in Escherichia coli of the large genomic segment of infectious pancreatic necrosis virus. AB - A complete cDNA clone of the larger A segment of the genome of infectious pancreatic necrosis virus (IPNV) was expressed in Escherichia coli in an effort to develop a vaccine for IPNV in fish. When the cDNA insert was positioned in the correct orientation to the pUC19 lacZ promoter, the viral proteins VP2, NS, and VP3 were synthesized and processed as observed in infected cells. When the insert was placed in the opposite orientation, VP3 and a 38-kDa virus-specific polypeptide were also synthesized. In addition, specific deletions made from the 3' end into the NS gene of the cloned A segment led to inactivation of the NS proteolytic activity and subsequently, the synthesis of an unprocessed VP2-NS polyprotein precursor. Antiserum to this polyprotein distinguished NS (28.5 kDa) from VP3 (31 kDa) and led to the identification of a previously undescribed 38 kDa virus-specific polypeptide in infected cells. Thus, both internal translational initiation and proteolytic cleavage could lead to the synthesis of VP2, NS, and VP3 from a single mRNA with a single open reading frame. A trpE expression vector, pATH2, was used to synthesize large quantities of the A segment-encoded proteins in bacteria. The resulting bacterial lysate was very effective in inducing protective immunity in rainbow trout fry. PMID- 2219720 TI - Structure of the gene encoding the M1 protein of sonchus yellow net virus. AB - The gene encoding the M1 protein of sonchus yellow net virus (SYNV), a plant rhabdovirus, has been sequenced and identified by Western blot analysis of SYNV proteins using antibodies directed against a fusion protein derived from a portion of the sequenced gene. The M1 gene is positioned between nucleotides 4039 and 5109 relative to the 3' end of the viral RNA and is the fourth gene from the 3' end of the genome. The 1071-nucleotide (nt) M1 gene lies between a putative nonstructural gene of unknown function and the gene encoding the glycoprotein and is bordered on either side by the same GG intergenic dinucleotide that separates other genes in the SYNV genome. The M1 mRNA (scRNA 6) consists of a 71-nt untranslated region at the 5' terminus followed by an 858-nt open reading frame (ORF) capable of encoding a protein with a calculated molecular weight of 31,779. The amino acid sequence deduced from this ORF is not highly homologous to those of other rhabdovirus matrix proteins, but has some localized regions of similarity. The UGA codon that terminates the M1 ORF is followed by a 3' untranslated region of 142 nt. The viral RNA (minus-sense) sequence corresponding to the extreme 3' end of the mRNA contains a 9-nt tract (3'-AUUGUUUUU-5') that is identical to the sequences at the termini of other SYNV genes. PMID- 2219721 TI - Genetic variation and multigene families in African swine fever virus. AB - The genome of a virulent strain (LIS57) of African swine fever virus differs from that of the Vero-cell-adapted strain (BA71V) in several deletions located in the variable regions. The region which contains the most differences is located 8-20 kb from the left end. The DNA sequence of this region was obtained from LIS57 virus DNA and compared with the overlapping sequences of BA71V virus. This comparison revealed that the changes in the variable regions result in differences in the number of genes which belong to the multigene families 360 and 110. Virus isolate LIS57 contains at least 8 genes of the multigene family 360 and 12 genes of the multigene family 110, instead of the 6 and 5 genes, respectively, found in BA71V virus strain. The position of the deletions indicates that new combinations of multigene family members in African swine fever virus DNA may arise by in-frame recombination between homologous genes. These data indicate that the evolution of the multigene families 360 and 110 in African swine fever virus DNA has involved different processes, including gene duplication, divergence of duplicated genes, and gene deletion. PMID- 2219722 TI - The complete DNA sequence of vaccinia virus. AB - The complete DNA sequence of the genome of vaccinia virus has been determined. The genome consisted of 191,636 bp with a base composition of 66.6% A + T. We have identified 198 "major" protein-coding regions and 65 overlapping "minor" regions, for a total of 263 potential genes. Genes encoded by the virus were located by examination of DNA sequence characteristics and compared with existing vaccinia virus mapping analyses, sequence data, and transcription data. These genes were found to be compactly organized along the genome with relatively few regions of noncoding sequences. Whereas several similarities to proteins of known function were discerned, the function of the majority of proteins encoded by these open reading frames is as yet undetermined. PMID- 2219723 TI - A DNA ligase gene in the Copenhagen strain of vaccinia virus is nonessential for viral replication and recombination. AB - Biochemical and genetic analyses have been conducted to determine whether a vaccinia virus open reading frame (orf) with extensive homology to the Saccharomyces cerevisiae DNA ligase gene encodes a functional ligase activity. This orf in HindIII A, designated A50R, is capable of encoding a 552-amino-acid, 63.4-kDa polypeptide. Full-length A50R mRNA produced in vitro directed the synthesis of a polypeptide with an apparent molecular weight of 57 kDa. Significantly, translation reactions programmed with A50R mRNA were capable of ligating a 3-kb Notl restriction fragment into multimers. DNA ligase activity was not detectable when either truncated sense or full-length antisense mRNA was translated in vitro. In extracts prepared from cells infected with wt vaccinia virus, DNA ligase activity was detected as assayed by the formation of a 57 kDa ligase-AMP adduct which was expressed early in the viral replication cycle. In cells infected with a DNA ligase deletion mutant no equivalent AMP-labeled adduct was detected. Relative to wt virus, the DNA ligase deletion mutant exhibited no significant differences in homologous recombination. These results indicate that the vaccinia orf A50R encodes a functional DNA ligase expressed early in infection, but this DNA ligase is nonessential for either recombination or viral replication. PMID- 2219724 TI - Expression pattern of the hepatitis B virus genome in transfected mouse fibroblasts. AB - Permanent mouse fibroblast LTK- cells were transfected with dimeric hepatitis B virus (HBV) DNA linked to the simian virus 40 (SV40) early promoter/enhancer. Many clones stably expressed high levels of polyadenylated RNAs encoding hepatitis B surface (HBs) proteins (2.1 kb), HBe protein (3.6 kb), and HBx protein (0.6 kb). Although a chimeric RNA (4.0 kb) probably starting from the SV40 promoter was also synthesized, transcription of viral RNAs was predominantly directed by HBV promoters and its terminator. In contrast to HBV-transfected liver cells, the fibroblasts expressed only pregenomic 3.6-kb transcripts starting 5' to, but not within, the precore sequence. Thus, no normal core protein could be synthesized, but the cells expressed and secreted HBe protein of heterogeneous size. Small and middle HBs proteins were strongly expressed, while large HBs protein was almost absent. HBx mRNA expression was more efficient in mouse fibroblasts than in human hepatoma cells and 18-kDa HBx protein was exclusively detected in purified nuclei. Expression of HBe, small and middle HBs, and HBx proteins apparently does not require hepatic factors. Underexpression of HBc mRNA and large HBs mRNA suggests that activity of their promoters depends on cell-type-specific transcription factors. PMID- 2219725 TI - Replication of hepatitis B virus in transfected nonhepatic cells. AB - Permanent murine fibroblasts (LTK-) were transfected with a dimer of hepatitis B virus (HBV) DNA and a neomycin resistance gene which were both linked to the simian virus 40 (SV40) early promoter/enhancer. One of the stably transfected clones, LTK4/36, which secreted HBsAg, HBeAg, and HBV DNA was further analyzed. It contained eight to nine copies of integrated HBV DNA per haploid genome and low amounts of episomal HBV DNA. The secreted viral DNA was covalently linked to protein and was associated with particles which had the characteristic density of natural virions from serum of human viremic carriers. The particles contained an endogenous DNA polymerase, small and middle surface proteins, but in contrast to natural virions very little core protein and large surface protein. Instead of core protein, they contained incompletely processed HBe protein which is colinear to core protein. The fibroblast-derived virions were less stable than virions from human carriers or from transfected hepatoma cells. After several days of storage, their DNA was only partially protected against DNase. Obviously, nonhepatic cells can express HBV-like particles, even if liver-dependent gene products like large surface protein and core protein are missing. PMID- 2219726 TI - Expression of cauliflower mosaic virus gene I using a baculovirus vector based upon the p10 gene and a novel selection method. AB - A new baculovirus expression vector based upon the p10 gene of Autographa californica nuclear polyhedrosis virus (AcNPV) and a novel system for the screening of p10 recombinants have been developed. The insertion of a cassette containing the lacZ gene under the control of a heat-shock promoter of Drosophila melanogaster downstream from the cloning site in p10 transfer vectors allows the convenient identification of putative recombinants by virtue of their expression of beta-galactosidase. Using this p10 transfer vector an AcNPV recombinant was engineered with a cDNA copy of gene I of cauliflower mosaic virus (CaMV) in place of the p10 coding sequence. This p10 recombinant expressed CaMV gene I at levels equivalent to those of p10 and polyhedrin, and was shown to be as effective in producing this protein as recombinants exploiting the polyhedrin promoter. CaMV gene I protein formed large numbers of hollow fiber-like structures in the cytoplasm of infected cells. Because the polyhedrin gene remains intact, these p10 expression vectors may be exploited for the expression of heterologous proteins in insects infected per os and for the enhancement of baculovirus pathogenicity for insect control. PMID- 2219727 TI - Processing, assembly, and immunogenicity of human immunodeficiency virus core antigens expressed by recombinant vaccinia virus. AB - Recombinant vaccinia viruses that contained regions of the gag-pol open reading frames of human immunodeficiency virus type 1 (HIV-1) were constructed. Cells infected with recombinants containing both gag and protease genes expressed and processed HIV gag antigens efficiently. Processing was much reduced in cells infected with recombinants containing only gag, but not the protease gene. However, significant amounts of p41 were produced by protease-defective recombinants. This protein was immunoreactive with p24-specific monoclonal antibodies and was produced in a truncated form by a recombinant containing a 3' deletion in the p15 coding region of gag ORF. These results indicate that p41 could represent an alternative gag precursor with N-terminal sequences derived from p24 and C-terminal from p15. Ultrastructural analysis of recombinant infected cells revealed that the gag antigens expressed were assembled into retrovirus-like particles and were secreted into culture medium. This assembly process was not dependent on HIV protease function, because immature core particles were produced by recombinants lacking HIV-1 protease functions. Immunization of mice and chimpanzees with vaccinia-HIVgag recombinant viruses generated both antibody and cell-mediated immune responses to HIV gag antigens. These recombinants are therefore useful not only for studying HIV virion processing and assembly, but also for designing immunogens for the prophylaxis and immunotherapy against AIDS. PMID- 2219728 TI - The hemagglutinin of influenza B virus present in clinical material is a single species identical to that of mammalian cell-grown virus. AB - When clinical specimens of influenza virus are adapted to grow in embryonated hens' eggs, variants are selected which have specific amino acid substitutions in the hemagglutinin (HA). In contrast, a single virus, distinct from any egg adapted variant, is selected when virus is isolated on MDCK mammalian cell culture. We have utilized the polymerase chain reaction to determine the nature of the hemagglutinin of influenza B viruses present in clinical material prior to cultivation in the laboratory. Sequence analysis of individual clones of amplified DNA reveals that the HA of clinical virus is essentially homogeneous and identical to the virus derived on MDCK cells. The HA of egg-adapted virus was heterogeneous and nonidentical to that of the clinical material and of the MDCK derived virus. PMID- 2219729 TI - Factors affecting efficient infection of tobacco with in vitro RNA transcripts from cloned cDNAs of satellite tobacco mosaic virus. AB - Recombinant cDNA clones of the complete satellite tobacco mosaic virus (STMV) genome (1059 ribonucleotides) were constructed with unique Xbal and HindIII or Pstl restriction sites engineered at the 5' and 3' termini, respectively. The genome-length cDNAs were positioned downstream of T7 or SP6 phage promoters. Genome-sense RNAs transcribed in vitro from the T7 promoter were biologically active, while negative-sense RNAs transcribed in vitro from the SP6 promoter were not. Constructs that were identical to STMV and two other constructs in which there were two or six specific nucleotide differences in the 3' noncoding region yielded RNAs that were infectious. Sequence analysis of the progeny RNA derived from infections with transcripts containing nucleotide differences between nucleotides 682 and 753 revealed that these changes in sequence were maintained. In contrast, differences in the nucleotide sequence between nucleotides 989 and 1059 were not maintained in progeny RNA; one mutant reverted to the wild-type sequence, and the other generated a new sequence during infection. PMID- 2219730 TI - Cloning of the genome of a densovirus and rescue of infectious virions from recombinant plasmid in the insect host Spodoptera littoralis. AB - We have cloned an infectious genome of the Junonia coenia densonucleosis virus (JcDNV) into the bacterial plasmid pBR322. The viral genome could be rescued from the recombinant plasmid pBRJ by transfection of pBRJ DNA to sensitive Spodoptera littoralis larvae. pBRJ DNA produced a typical viral infection and a comparable percentage of larvae became infected following inoculation of equivalent amounts of purified virion DNA or cloned viral DNA. Virions extracted from transfected larvae were indistinguishable from wild-type (wt) virions with regard to their biophysical and biological properties. In particular, rescued virions were as infectious as wt virions and showed identical restriction profiles of their genome. In contrast, subcloning of JcDNV DNA deleted at both extremities of a sequence of ca 250 or ca 100 bp resulted in the inability of the recombinant plasmids to initiate a viral infection. These data suggest that, as for vertebrate parvoviruses, the inverted terminal repeats display essential functions in the rescue process and replicative cycle of densoviruses. This is the first report of the molecular cloning of the infectious genome from an insect parvovirus, and more generally from an invertebrate virus. pBRJ should provide an efficient tool to further define the organization of the JcDNV genome and compare it to other parvoviruses. PMID- 2219731 TI - Selective inhibition of hepatitis B virus and human immunodeficiency virus sequence-promoted gene expression by cotransfected poly(I):poly(C). AB - The transient expression of hepatitis B virus (HBV) surface and "eJ" antigens caused by transfection of human hepatoblastoma HepG2 cells with HBV DNA was markedly inhibited by cotransfection with poly(I):poly(C). Cotransfection with poly(I):poly(C) also inhibited the expression of bacterial chloramphenicol acetyltransferase (CAT) gene which was under the control of either the HBV core promoter or the human immunodeficiency virus (HIV-1) long terminal repeat. This inhibition was much more pronounced on the expression of HBV-promoted CAT than HIV-promoted CAT. The uptake of reporter plasmid was not affected by cotransfected poly(I):poly(C). The inhibition was found to be at the steady-state CAT mRNA level and appeared to be specific for HBV and HIV regulatory sequences since CAT expression directed by other viral and cellular regulatory sequences was not inhibited. Cotransfection with a mixture of equal amounts of poly(I) and poly(C) had similar inhibitory effects whereas cotransfection with poly(l) or poly(C) alone, or other double-stranded ribo- or deoxyribonucleotides, did not have such strong effects. The addition of poly(l):poly(C) to the culture medium of cells transfected with these reporter plasmids caused little inhibition. Transfection with poly(l):poly(C) induced a minimal amount of intracellular interferon-alpha in HepG2 cells which may be involved in selective inhibition of HBV-and HIV-1-directed gene expression. 2-Aminopurine, an inhibitor of double stranded RNA activated protein kinase known to block interferon gene induction by poly(l):poly(C), partially reversed the poly(l):poly(C)-induced inhibitory effect on HBV-CAT expression. PMID- 2219732 TI - Sequence analysis of rice dwarf phytoreovirus genome segments S4, S5, and S6: comparison with the equivalent wound tumor virus segments. AB - The complete nucleotide sequences of genome segments S4, S5, and S6 of rice dwarf phytoreovirus (RDV) were determined. S4 and S5 consist of 2468 and 2570 base pairs, respectively, S5 thus being larger in size than S4, contrary to the situation suggested by their relative migration in a polyacrylamide gel. S6 is 1699 nucleotides long. The individual segments have segment-specific inverted repeats adjacent to the conserved terminal sequences (5'GGUAAA---UGAU3' for S4, 5'GGCAAA---UGAU3' for S5 and S6). S4, S5, and S6 each have single long open reading frames encoding 727, 801, and 509 amino acids, respectively. A low level of amino acid sequence homology was observed between RDV S4 and wound tumor virus (WTV) S4 (22.4%), and between RDV S6 and WTV S6 (20.2%). On the other hand, RDV S5 and WTV S5 show 52.0% amino acid sequence similarity, indicating that S5 is much more conserved than any other segments of RDV and WTV reported so far. Further comparative analyses indicate that the RDV segment shows a greater frequency of usage of codons XYG and XYC, and much less frequent usage of codon XYA than the equivalent WTV segment, this codon preference bias being more conspicuous than expected from the base contents. PMID- 2219733 TI - Sequence analysis of the rice dwarf phytoreovirus segment S3 transcript encoding for the major structural core protein of 114 kDa. AB - The primary structure of rice dwarf phytoreovirus (RDV) genome segment S3 was determined. RDV S3 consists of 3195 nucleotides. A 14-bp segment-specific inverted repeat is located immediately adjacent to the conserved terminal sequence (5'GGCAAA---UGAU3'). A single long open reading frame encoding for 1019 amino acids with an Mr of 114,289 is also identified. In order to investigate the localization of the predicted polypeptide, we determined the amino acid sequence of the 26-kDa peptide fragment obtained from the structural core protein digested by Staphylococcus aureus V8 protease. The sequence of the fragment was found in the translational product presumed from the nucleotide sequence of RDV S3, indicating that RDV S3 encodes the major structural core protein of 114 kDa. PMID- 2219734 TI - Reovirus protein sigma 1 translated in vitro, as well as truncated derivatives of it that lack up to two-thirds of its C-terminal portion, exists as two major tetrameric molecular species that differ in electrophoretic mobility. AB - Reovirus protein sigma 1 is the cell attachment protein that modulates tissue tropism and the nature of the antiviral immune response. This protein is present in reovirus particles in the form of 12 tetramers that are associated with the projections or spikes. We have analyzed a series of deletion mutants of protein sigma 1 in order to localize its oligomerization domain and found that progressive deletion from the C-terminus fails to affect ability to oligomerize, even when the deletion extends into the N-terminal heptapeptide repeat region. It was also found that native tetrameric protein sigma 1 synthesized in vitro, as well as its truncated derivatives, exists in two forms that differ in electrophoretic mobility. Possible reasons for this are discussed. PMID- 2219735 TI - Adenovirus type 2 precursor proteins are cleaved by proteinases of other adenoviruses. AB - A virus-encoded endoproteinase is responsible for the cleavage of adenovirus type 2 (Ad2) precursor proteins. By analyzing the genetic maps of previously characterized interserotypic recombinants between Ad2 and Ad5 and by means of an in vitro proteinase assay using Ad1, 2, 3, 4, 5, 6, 7, 9 as the source of enzyme, it was demonstrated that (i) the enzyme was present in these serotypes and by extension it is likely to be present in all adenoviruses, and (ii) that proteolytic cleavage can take place efficiently even between widely different serotypes. These attributes suggest a high degree of sequence conservation of the enzyme and substrate cleavage sites, thus designating proteolytic processing as an excellent target for chemotherapy. PMID- 2219736 TI - Heterogeneity of Nef proteins in cells infected with human immunodeficiency virus type 1. AB - Human T-lymphocytic cell line H9 infected with the HTLV-IIIB isolate of human immunodeficiency virus type 1 (HIV-1) synthesizes two forms of the Nef protein (p25 and p27) that differ both in molecular weight and charge. Different subpopulations of viruses were isolated from the HTLV-IIIB stock which induce expression of only p25 or p27. Cells infected with HIV-1 derived from the HXB3 clone of the HTLV-IIIB isolate made only the p25 species, whereas the 8E5/LAV cell line which harbors a single defective LAV provirus produces only the p27 species. These findings are consistent with the notion that the HTLV-IIIB isolate consists of at least two distinct variants with different nef genes, one specifying p25 and the other encoding p27. After a considerable number of passages in culture, H9 cells chronically infected with the HTLV-IIIB isolate produced high levels of p25 and lower levels of p27. Passages in culture appear to select for a subpopulation of virus variants that specify high levels of p25 Nef expression. PMID- 2219737 TI - Effect of two novel inhibitors of the human immunodeficiency virus protease on the maturation of the HIV gag and gag-pol polyproteins. AB - The ability of two novel synthetic compounds to inhibit the HIV protease-mediated processing of HIV-1 precursor polyproteins was investigated in an in vitro gag protease mixed lysate assay system and in an assay using recombinant baculoviruses engineered to express the HIV-1 gag and pol genes in cultured insect cells. With the in vitro mixed lysate assay we have shown that both compounds at 1 microM can completely inhibit the HIV-1 and HIV-2 protease mediated release of p24 from the HIV-1 gag precursor at pH 5.5 and pH 7.0. In the intracellular baculovirus system these compounds were shown to inhibit the protease-mediated maturation of gag and also the excision of the protease moiety from its precursor. PMID- 2219738 TI - Palmitoylation of the influenza A virus M2 protein. AB - The M2 proteins of a variety of influenza A viruses of different subtypes were shown to possess associated palmitate. Susceptibility to removal by reduction or treatment with hydroxylamine is consistent with attachment via a thioester linkage to cysteine. The absence of the acyl group from the M2 proteins of several equine viruses of the H3N8 subtype correlates with the replacement of cysteine 50 with phenylalanine and points to this as the site of palmitate attachment. PMID- 2219739 TI - Terminal structure of a Densovirus implies a hairpin transfer replication which is similar to the model for AAV. AB - We cloned the complete sequence of Bombyx DNV (Ina isolate; Bm DNV-1) genome in a bacterial plasmid pUC 119 and determined the nucleotide sequences of both termini, resulting in elucidation of the nucleotide sequence of the complete genomic DNA of DNV. The complete sequence of the DNV DNA (5048 nucleotides) has inverted repeats of 225 nucleotides and the terminal 153 nucleotides are palindromic. The palindromes can fold back on themselves to form a hairpin structure but, unlike AAV, the small internal palindrome which forms a T-shaped conformation was not observed. End-label analysis demonstrated that the palindromic sequences at both termini can exist in either of two orientations (flip or flop) in virion DNA with different frequencies. These data suggest that the hairpin transfer model for AAV replication must be modified to explain the DNV replication. Additionally, a comparison study on the terminal structures of insect, human, and rodent parvoviruses allowed a prediction on the ancestral terminal structure of parvovirus genome. PMID- 2219740 TI - A new hepatitis B virus variant in a chronic carrier with multiple episodes of viral reactivation and acute hepatitis. AB - To examine whether there are HBV variants not yet described which cannot express HBe due to a mutation in the pre-C region, and, if they exist, whether they cause a particular course of infection and disease, we analyzed the HBV genomes of a HBs/anti-HBe positive chronic carrier who had several episodes of acute reexacerbations of chronic hepatitis with at least two viremic phases. Direct sequencing of the precore/core and the pre-S regions of the HBV sequences of both viremic phases amplified by the polymerase chain reaction revealed that they were very similar to each other but substantially divergent from published HBV genomes. Both virus populations contained a mutation in the first nucleotide of the pre-C translation initiation codon (AUG/CUG) which prevents HBeAg expression. These data demonstrate the existence of a new HBV variant which can enter a latent phase from which it can be reactivated with acute reexacerbation of liver inflammation. PMID- 2219741 TI - Genetic analysis of tomato golden mosaic virus: ORF AL2 is required for coat protein accumulation while ORF AL3 is necessary for efficient DNA replication. AB - Tomato golden mosaic virus (TGMV) is a geminivirus whose genome is divided between two DNA components, designated A and B. The TGMV genome contains six open reading frames (ORFs) which can encode proteins of greater than 10 kDa. We have used a protoplast transfection system to determine the effects of viral proteins, as defined by these ORFs, on the accumulation of viral DNA in infected cells. The accumulation of cost protein was also examined in leaf discs. Our results indicate that mutations in ORFs AR1 and AL2 do not affect viral double-stranded DNA (dsDNA) levels, although AR1 and AL2 mutants accumulate only small amounts of single-stranded viral DNA (ssDNA). In contrast, a large reduction in both ss- and dsDNA levels is observed when a mutation is introduced into ORF AL3. Mutations within either of the two DNA B ORFs do not affect DNA replication. The AL3, BR1, and BL1 mutants are capable of synthesizing coat protein; however, coat protein is not detected in leaf discs inoculated with AR1 or AL2 mutants. Testable models are proposed to explain the influence of AL2 protein on coat protein accumulation and to account for the stimulation of viral DNA synthesis mediated by the AL3 gene product. PMID- 2219742 TI - In vitro DNA replication by cytoplasmic extracts from cells infected with African swine fever virus. AB - A cell-free system that catalyzes DNA replication was prepared from cytoplasmic extracts of Vero cells infected with African swine fever virus (ASFV). The cells were permeabilized with lysolecithin and disrupted by mild mechanical action and the nuclei were removed by low-speed centrifugation. Extracts prepared from infected cells at the time of maximal DNA replication incorporated [alpha 32P]dTTP into acid-insoluble material that was sensitive to DNase and resistant to RNase. The reaction was inhibited by phosphonoacetic acid, an inhibitor of ASFV-specific DNA polymerase. Extracts from mock-infected cells had a negligible activity. Micrococcal nuclease-treated extracts were able to replicate added virion DNA or viral replicative DNA. An increase in the mass of DNA detected by ethidium bromide staining and by dot blot hybridization with ASFV DNA showed that the incorporation was due to true replication. Plasmid DNA was also replicated, which indicates that ASFV-specific DNA polymerase does not require a virus specific origin of replication. The pattern of fragments generated by EcoRI digestion of the in vitro product was characteristic of viral replicative DNA. Hybridization with a recombinant plasmid containing a terminal fragment of ASFV DNA confirmed the presence of dimer terminal ASFV fragments presumably generated from concatemeric replicative intermediates. PMID- 2219743 TI - The N-terminal quarter of reovirus cell attachment protein sigma 1 possesses intrinsic virion-anchoring function. AB - Previously the receptor recognition domain of the reovirus serotype 3 (T3) cell attachment protein (sigma 1) was mapped to the C-terminal half of the protein using deletion mutagenesis of the reovirus S1 gene. A similar approach has been adopted in the present study to map the domain on T3 sigma 1 that is responsible for incorporation into the virion (i.e., the anchoring domain). Restriction enzymes which divide the T3 S1 cDNA into four segments (5'-I-II-III-IV-3') of similar size were used to generate four mutants, each with a particular segment deleted. The mutants were cloned into SV40 expression vectors and used to transfect COS-1 cells which were subsequently with reovirus serotype 1. Progeny viral particles with truncated T3 sigma 1 proteins incorporated were then identified by radioimmunoprecipitation with a serotype-specific anti-T3 sigma 1 serum. It was found that the mutant lacking I (mutant dl) was totally incapable of being incorporated into the virion, whereas the mutant lacking domain II (mutant dII) was incorporated efficiently. Due to altered antigenicities of the mutants lacking domain III (mutant dIII) or domain IV (mutant dIV), incorporation of these two proteins into virions was less detectable using the above assay. Evidence that domain I (the N-terminal 121 amino acids) alone dictates the incorporation of sigma 1 into the virion came from the subsequent demonstration that a chimeric protein containing domain I fused to chloramphenicol acetyltransferase (CAT) was incorporated into the virion (detectable with an anti CAT serum) as efficiently as the full-length sigma 1 protein. PMID- 2219745 TI - Retinal ganglion cell distribution and behaviour in procellariiform seabirds. AB - Retinal ganglion cell distribution in nine species of procellariiform seabirds was studied by Nissl staining of retinal whole-mounts and the construction of density contour maps. Most species showed a horizontal linear area of high cell density, but concentric distributions with dorsal and central cell concentrations were found in two species. These results are discussed in relation to the birds' foraging behaviour. PMID- 2219744 TI - Spatial properties of horizontal cell responses in the cat retina. AB - The spatial properties of horizontal cells in the cat retina have been studied by means of intracellular recordings in the optically intact, in situ, eye. The spread of potentials in the horizontal cell layer and the spatial summation properties have been investigated using "white light" stimuli in several different configurations. Area-response curves were measured with flashing spots carefully centered on the receptive field. The lateral spread of potentials was studied using long, narrow slits of light and circular spots of different sizes at different positions in the receptive field. Two-dimensional receptive field profiles showed that the receptive field structure was, both on a large scale and at higher resolutions, relatively homogeneous and isotropic. The size and shape of the receptive fields have been characterized by applying a simplified version of the model proposed by Naka and Rushton (1967) of electrical coupling in the horizontal cells layer in fish. Results show that the model describes the variation of response amplitude reasonably well both as a function of spot size and spot or slit position. However, deviations were found for area-response curves measured at higher light intensities and for receptive field profiles measured with relatively small spots. Furthermore, the estimated length constants resulting from the different experiments were not in agreement. Different model parameters were needed in order to describe the spatial summation properties and the lateral spread of potentials respectively. It is concluded that passive electrical spread and linear summation of potentials cannot account for the observed spatial properties. PMID- 2219746 TI - Age-related changes in the morphology, absorption and fluorescence of melanosomes and lipofuscin granules of the retinal pigment epithelium. AB - The morphological and spectral characteristics of purified populations of melanosomes and lipofuscin granules from the human retinal pigment epithelium (RPE) were studied with respect to donor age. All melanosome and lipofuscin fractions exhibited the typical ultrastructural appearance associated with these granules. Absorption profiles of both melanin and lipofuscin granules demonstrated an increased optical density of the granules with increasing age. The former was associated with an overall increase of melanin within the granules. Melanosomes were weakly fluorescent; emission in the blue decreased with increasing age while emission in the red increased. The fluorescent intensity of lipofuscin granules increased with age. These results provide support for the concept that melanogenesis is occurring within the human RPE throughout life and that pigment granules within the RPE undergo age-related modifications during life. PMID- 2219747 TI - Salience of chromatic basic color terms confirmed by three measures. AB - Using single color terms of their choice, nine subjects named each of 424 colors twice under carefully-controlled conditions. Compared to any other color names, the chromatic basic color terms (red, green, yellow, blue, orange, purple, brown and pink) are all used more consistently within subjects, with greater consensus between subjects, and with shorter mean response times; there is no overlap between the two categories of color names by any of these criteria. The results are interpreted as supporting the conception that basic color terms refer to fundamental sensations for which there is a specific physiological basis. PMID- 2219748 TI - Motion coherence in infants. AB - Two perpendicular square-wave gratings (i.e. plaids) were used to investigate motion coherence in 1-, 2- and 3-month-old infants. The direction of motion of the stimulus was judged by an adult observer, on the basis of the induced optokinetic nystagmus (OKN) in an eight-alternative eye movement voting paradigm. Infants as young as 1 month of age demonstrated OKN in the direction consistent with motion coherence. There was no significant difference among the performances of 1-, 2- or 3-month-old infants. However, the percentage of trials on which infants demonstrated OKN in the coherence direction was less than that obtained from adults tested with the same paradigm. Movshon, Adelson, Gizzi and Newsome (1985) have suggested that the cohered motion of a complex pattern may be processed after the orientation of the components of the pattern, perhaps in the middle temporal area of the visual cortex (MT). The present results suggest that either young infants and adults process the motion of complex patterns similarly or that the OKN consistent with the direction of motion coherence observed in infants involves subcortical nonoriented visual centers rather than the higher level process which is presumed to occur in adults. PMID- 2219749 TI - Spatial-frequency discrimination of drifting gratings. AB - Spatial-frequency discrimination thresholds were measured for briefly (300 msec) presented sinewave gratings having a contrast one logarithmic unit above detection threshold. The gratings were drifted at rates varying from 1.1 to 40 Hz. In a two-interval forced-choice paradigm thresholds were determined for vertically and obliquely oriented gratings. Three reference spatial frequencies (1, 4, 12 c/deg) were tested. For the 1 c/deg reference spatial frequency, spatial-frequency discrimination thresholds were constant over the wide range of drift rates used. For 4 and 12 c/deg reference gratings, discrimination thresholds were constant for drift frequencies up to 14 Hz. For drift frequencies beyond 14 Hz, spatial-frequency discrimination thresholds increased abruptly, rising from approx. 6% at 14 Hz to 25% at 40 Hz drift rate. Measurements with obliquely oriented gratings yielded comparable results. The increase in the spatial-frequency discrimination threshold for medium-high spatial frequencies and high temporal frequencies might reflect an increase in the spatial frequency bandwidth of the mechanisms sensitive to these stimulus frequencies. PMID- 2219750 TI - Perception of directional sampled motion in relation to displacement and spatial frequency: evidence for a unitary motion system. AB - Perception of directional motion was studied by displaying two images (F1 and F2) in rapid succession. The two images were identical except for a horizontal displacement of F2 with respect to F1. Observers reported the direction of horizontal motion over a wide range of displacements. The stimuli in Experiment 1 were one-dimensional gratings with spatial frequency between 0.125 and 6 c/deg. Motion was seen at all displacements to almost 0.5 cycles (counterphase) and remained invariant across spatial frequencies. In Experiment 2 the stimuli were band-pass filtered random-dot patterns. The bandwidth of the filters was 1 octave, and centre frequencies ranged from 0.75 to 12 c/deg. In every case, the response functions exhibited quasi-periodic oscillations related to structural properties of the images. One-dimensional analyses based on autocorrelation did not provide a satisfactory account of the data. By contrast, the data were fitted successfully by a two-dimensional analysis that integrated the responses of neighbouring motion detectors so as to yield a smooth motion flow field from which left-right directional motion could be derived. Practically and conceptually, the outcome supports a unitary motion system as distinct from separate systems subserving short-range and long-range motion. PMID- 2219751 TI - Foveating saccades. AB - A review of the literature revealed that foveating saccades were found to be faster than other fast eye movements (FEMs) except optokinetic nystagmus (OKN) quick phase. In the present experiment, foveating saccades were compared to OKN quick phase in humans and were found to have higher maximum speeds and shorter durations. Unlike previous experiments, foveating saccades were made to targets at unpredictable distances, and active pursuit during OKN was discouraged. Previously reported differences between the speeds of foveating saccades and saccades to remembered target positions were replicated. Foveating saccades, therefore, can be distinguished from other FEMs on the basis of speed. This behavioral difference suggests that a distinctive mechanism exists for foveating targets. PMID- 2219752 TI - Readily visible changes in color contrast are insufficient to stimulate accommodation. AB - In an earlier study (Wolfe & Owens, 1981) it was reported that humans could not accommodate to an insoluminant red-green border. However, recent masking studies (Switkes, Bradley & DeValois, 1988) have shown that, using an appropriately normalized contrast metric, contrast decrements similar to those produced by defocus are equally visible for color or luminance modulated grating patterns. We have compared accommodative responses to 1.75 c/deg gratings that consisted of either isochromatic luminance modulations or isoluminant red-green color modulations. All four observers could accommodate accurately to luminance modulated gratings over a wide range of contrasts. However, no appropriate accommodative responses were obtained even for the highest contrast color modulated gratings. These results show the changes in color contrast are ineffective as stimuli for the human accommodative response even when the changes in chromatic contrast accompanying defocus are readily perceived. PMID- 2219753 TI - Detection of an orientation singularity in Gabor textures: effect of signal density and spatial-frequency. AB - This work presents evidence for a second stage of spatial filtering in early vision. This second stage operates on the output of the well known linear spatial filters and integrates their thresholded responses with a center-surround weighting function. The evidence for the existence of this second stage comes from experiments where observers have to detect a Gabor signal with known parameters (target) among a varied number of other Gabor signals having orthogonal orientation (distractors). Detection performance on this task depends on the number of distractors and the distance between them: when the number of distractors is small performance deteriorates with an increasing number of distractors; however, when the number of distractors becomes larger performance improves with an increasing number of distractors. This improvement depends on the spatial-frequency of the signals and their spatial separation. Best performance is achieved when the spatial separation between signals is larger than three times their center wavelength but smaller than nine times their wavelength, implying a second stage filtering with a center size of six wavelengths and a total size of 18 wavelengths. This second stage of filtering may underlie our ability to detect certain texture boundaries preatentively. PMID- 2219754 TI - Optimal displacement in apparent motion and quadrature models of motion sensing. AB - A grating appears to move if it is displaced by some amount between two brief presentations, or between multiple successive presentations. A number of recent experiments have examined the influence of displacement size upon either the sensitivity to motion, or upon the induced motion aftereffect. Several recent motion models are based upon quadrature filters that respond in opposite quadrants in the spatiotemporal frequency plane. Predictions of the quadrature model are derived for both two-frame and multiframe displays. Quadrature models generally predict an optimal displacement of 1/4 cycle for two-frame displays, but in the multiframe case the prediction depends entirely on the frame rate. PMID- 2219755 TI - [Selected anthropometric findings in women with disorders of glucose tolerance with hypertension]. AB - In a group of 26 women with an impaired glucose tolerance anthropometric measurements of basic somatometric characteristics were made with special attention to the subcutaneous fat distribution and compared the findings with the healthy Czech population. Changes in body build, BMI, subcutaneous body fat distribution were evaluated and the causality of the relationship between blood pressure and gluteofemoral and abdominal obesity was investigated. From the author's observations ensues that in the group of women with impaired glucose tolerance overweight was recorded, as compared with the normal population, disproportions in the circumferences of the trunk and extremities, an excessive percentage of body fat, well developed muscles. In abdominal obesity a significant increase of the blood pressure and BMI was found. PMID- 2219756 TI - [The effect of streptozotocin-induced diabetes treated with insulin on the metabolism of calcium, magnesium and phosphorus]. AB - In a group of rats with streptozotocin induced diabetes the excretion of calcium, magnesium, phosphorus and creatinine in urine was investigated and the calcium, magnesium and phosphorus content of bone in relation to the duration of the disease. The authors observed that in diabetic rats the urinary losses of calcium, magnesium and phosphorus increase significantly. The creatinine excretion is also significant but lower in relation to calciuria and therefore the value of Nordin's index in diabetic rats rises markedly. Bone of diabetic rats in the early stage of diabetes (32 days) loses magnesium, while the calcium and phosphorus content does not change significantly. During longer persistence of severe diabetes (70 days) a significant drop of all three minerals in bone was observed. The bones of diabetic animals on the 70th experimental day were macroscopically smaller and were very fragile. The authors' findings suggest a marked influence of streptozotocin diabetes on calcium phosphate metabolism and bone metabolism, in particular on account of STZ diabetes, on an early drop of magnesium in bone. The possible impact of this finding for clinical practice will have to be tested further. PMID- 2219757 TI - [Changes in magnesium and ionized calcium serum levels in disorders of glucose tolerance]. AB - In a group of 58 subjects with a strictly defined glucose tolerance (38 normal- nGT, 10 impaired glucose tolerance--pGT, 10 type II diabetics treated by diet) the authors investigated the mutual relationship between changes in the blood sugar level and insulin serum level in relation changes of calcium, ionized calcium, magnesium and total proteins. In addition to expected differences in the native blood sugar level and insulinaemia, the authors found in pGT group in reduction of ionized calcium and magnesium on fasting. In the course of the oGTT in pGT group there is a rise of ionized calcium and magnesium and thus the changes, as compared with the initial value, differ significantly from changes in subjects with a normal glucose tolerance and in type II diabetics. The differences in the pattern total calcium are less marked, the changes of total protein did not differ. Evaluation of correlations revealed a only significant relationship between the change of ionized calcium and blood sugar level after 120 mins, in DM II. The findings suggest a different calcium and magnesium metabolism after a glucose load in subjects with an impaired glucose tolerance. It is not clear whether a cause of the disorder is involved or a possible compensatory mechanism. The clinical impact will have to be examined. PMID- 2219758 TI - [Anticoagulantion and antiaggregation therapy in patients with unstableangina pectoris]. AB - Heparin, aspirin with dipyridamol or 5% dextrose were administered to 266 patients admitted to the coronary unit with unstable angina. All patients were concurrently treated with isosorbide dinitrate, a beta-blocker and nifedipine. The number of patients who developed an acute myocardial infarction (IM) during the subsequent 72 hours was comparable in all three groups. However, in the heparin treated group only 3.2% patients developed Q IM, as compared with 20% patients treated with aspirin and dipyridamol (p = 0.005) and with 19% in the control group (p = 0.006). The magnitude of the IM was evaluated according to the highest serum value of creatine phosphokinase. In the heparin treated group its value was 810.5 +/- 538 i.u./l which was significantly less than in the aspirin + dipyridamol group where it was 1229 +/- 829 i.u./l (p = 0.048) and in the control group where it was 1417 +/- 919 i.u./l (p = 0.009). The authors defined the group of patients with a high risk of development of IM who had protracted anginous pain longer than 45 mins. with ST segment depression deeper than 1 mm on the ECG on admission. 55% of these patients developed an infarction in the course of the subsequent 72 hours. PMID- 2219759 TI - [Detection of atrial septal defects using esophageal echocardiography]. AB - By means of transoesophageal (oesophageal) echocardiography (TEE) the authors examined a group of 20 subjects. In 10 there was clinical suspicion (physical finding, ECG, X-ray) of an atrial septal defect. Common precordial echocardiographic examination (TTE) and dilution of indocyan green by means of an acustic sensing unit were negative or only marginally positive and did not provide a final decision. By means of TEE the defect was confirmed in 8 subjects by the finding of anatomical discontinuity of the septum and the presence of coloured Doppler shunt flow. In two subjects the finding was negative, in 10 controls no pathological findings were detected. The authors confirmed that TEE is a reliable method which proves even slight shunts in the area of the atrial septum. It is probably the most sensitive existing method. PMID- 2219760 TI - [Diagnosis of acute dissection of the aorta]. AB - The authors present a group of 14 patients (9 men and 5 women) aged 38-76 years (mean age 59 years) who were hospitalized during the five-year period between 1984 and 1988 at the medical department A of the Regional Institute of National Health in Banska Bystrica on account of acute dissection of the aorta. The authors describe clinical manifestations which can lead to suspicion of this serious disease. They make the readers familiar with their experience with ultrasonic and X-ray examination (in particular aortography and computed tomography). They analyze their contribution to the diagnosis of acute dissection of the aorta. PMID- 2219761 TI - [Cardiac function and adrenergic regulation in incipient hyperthyroidism]. AB - The authors investigated in 14 euthyroid women the action of triiodothyronine administered for 7 days, 100 micrograms per day. It was revealed that after the administration of triiodothyronine the duration of the preejection period of the systole was reduced as well as the index of the preejection period and the index of the electromechanical systole, and the weight declined. At the same time the authors recorded a drop of the plasma noradrenaline and adrenaline level, of the serum cholesterol and thyroxine concentration. The serum triiodothyronine level increased and correlated inversely with the duration of the preejection period. Triiodothyronine administration had no effect on the heart rate, Q-Kd interval, blood pressure and plasma concentration of cyclic adenosine monophosphate. The authors conclude from the findings that in triiodothyronine-induced hyperthyroidism the first cardiac effect of the administered hormone is enhanced contractility of the heart, this change being due to the direct effect of triiodothyronine not mediated by catecholamines. PMID- 2219762 TI - [Comparison of 2 methods for determination of antibodies to thyroglobulin in clinical practice]. AB - The authors compared the results of two methods for the estimation of antibodies against thyroglobulin: the principle of the Thymune-T test (Wellcome) is a haemagglutination method; parallel examinations were made by the author's modification of the radiochemical coprecipitation test (RCT). The laboratory results were evaluated in a large clinical group of patients with different types of thyroid disease. It was confirmed that the haemagglutination method gives more frequently positive results than the radiochemical test, in particular in the range of low titres. The chi square test provided, however, evidence that between methods a significant correlation exists. Although the results of the two tests are not necessarily identical in individual patients, it may be stated that RCT is an adequate method of choice, as it is simpler, more rapid and cheaper, and that it can be done in large series with objective automated evaluation of data. PMID- 2219764 TI - [Campylobacter pylori and treatment of duodenal ulcer]. AB - The authors subjected to endoscopic examination 90 patients with duodenal ulcers. From each patient they collected a bioptic specimen of the gastric antrum and duodenal bulbus for microbiological and histological examination. They found that for detection of C. pylori the microscopic examination was most useful. The presence of C. pylori in the gastric antrum was detected in 87% of the subjects and in the duodenal bulb only in 48%. The difference is significant at the 0.01 level. To 43 patients of the group Ranitidine was administered. The ulcer was cured within 4 weeks in 35 subjects. Ranitidine did not affect the presence of C. pylori and antral gastritis. After cure of the ulcer the authors administered Tarivid to 10 patients with persisting C. pylori positivity. The presence of C. pylori and antral gastritis were not affected by this treatment. PMID- 2219763 TI - [Subclinical hypothyroidism]. AB - Subclinical hypothyroidism was detected in 5.7% of 853 patients referred for ambulatory examination to a department in Prague. In patients referred with a mild degree of subclinical hypothyroidism with an evaluated level of thyrotropic hormone in serum (TSH) no significant deviations of serum thyroxine and triiodothyronine (T4 and T3) were found nor different values of the Achilles tendon reflex time, as compared with patients with normal thyroid function. In case of a more marked grade of subclinical hypothyroidism with an elevated TSH level without stimulation the patients have on average significantly lower T4 vales, significantly longer Achilles tendon reflex times and preejection stage of left ventricular contraction, and of Rodbard's Q-Kd interval (Q-Kd) than euthyroid patients. The values are, however, still within the reference range for normal function and in individual cases cannot be decisive for establishment of the diagnosis. The authors discuss the differential diagnosis and views on treatment of this disease. PMID- 2219765 TI - [Tenoxicam in the long-term treatment of active rheumatoid arthritis]. AB - The authors present the results of six months treatment with Tenoxicam (Tilcotil) in 30 patients with active rheumatoid arthritis. In no instance was it necessary to discontinue treatment, only one female patient complained of transient vertigo. During the final evaluation of the therapeutic effect as regards painfulness, sensitivity on palpation, oedema, restriction of movements, the author did not observe a satisfactory effect only in 8.5-24%. As regards hand grip, 20 m walk and consumption of analgesics the effect was also very satisfactory. Only four patients used occasionally Paracetamol or Alnagon, 1-2 tablets per day. The results achieved with this treatment indicate that it is a very good preparation suited for prolonged therapy of active rheumatoid arthritis, incl. patients of advanced age. Tenoxicam is particularly suited for a single dose per day (20 mg). It can be recommended also combined with gold therapy and treatment with antimalaric drugs. PMID- 2219766 TI - [An unusual case of prolonged hypoglycemia]. AB - The author described a case of protracted hypoglycaemia in a young type I insulin treated diabetic, associated at first with neurological symptomatology imitating a cerebrovascular attack. After three days, when it was necessary to administer repeatedly glucose by the i.v. route on account of low blood sugar levels, the carbohydrate metabolism deteriorated and called for administration of similar insulin doses as before. In the discussion the author deals with pathogenetic possibilities of the described condition. PMID- 2219767 TI - [Pathogenic aspects of diabetic macroangiopathy]. AB - Diabetics of both types suffer more frequently from atherosclerosis of the coronary, cerebral and peripheral arteries than the non-diabetic population of similar age groups. In the pathogenesis of atherosclerosis in diabetes an important part is played by the very frequent association of the diabetic syndrome with hyperlipoproteinaemia and hypertension, elevated levels of substances potentially toxic for the endothelium such as glucose, chylomicron remnants, sorbitol, immunocomplexes, CO and others. Changes of thrombocyte functions and of the equilibrium of the system prostacycline-thromboxane as well as disorders at different sites of the haemocoagulation an fibrinolytic cascade, no doubt, interfere in a negative way with the process of atherogenesis. Non enzymatic glycosylation of various proteins probably is also of a certain importance for the process of atherogenesis. The genetic background of the individual has obviously an impact on atherosclerotic complications in diabetics of type 2 (U-allele) where potential atherogenic hyperinsulinaemia is one of the constant manifestations of the disease. The second form of macroangiopathy (mediocalcinosis) affects practically only diabetic subjects and is probably due to the denervation of the blood vessels of the extremities in diabetic neuropathy. Identification and influencing of risk factors of macroangiopathy could have a favourable effect on the quality of life and prognosis of diabetic patients. PMID- 2219768 TI - [Treatment of hyperglycemic coma states in diabetics]. AB - In the treatment of acute decompensation of diabetes, diabetic ketoacidosis and hyperosmolar non-acidotic syndrome the basic demand is insulin administration--in small doses by the i.v. route, preferably by means of an injectomat in a permanent infusion. An alternative method for departments which do not possess a suitable infusion pump, is fractionated administration of small insulin amounts into the vein after 30 minute intervals. Equally important is rehydration treatment with saline; only in case of hypernatriaemia above 150 mmol/l the author recommends 0.45% NaCl. Acidosis in DKA is corrected by sodium bicarbonate only at pH 7.1 or less. As to K cations, the replacement of potassium ions is most important; the value of substitution of other cations (Ca, Mg) is doubtful and is not currently done, the same applies to phosphate anion replacement. It has not been proved that prevention of thromboembolic complications by heparin is expedient in these conditions. PMID- 2219769 TI - [Treatment of acute pulmonary edema]. AB - The authors give an account of treatment of acute pulmonary oedema. Their account is based on contemporary data in the literature and their own experience. Some aspects of the therapeutic procedures are described in detail. The review should serve as a practical guide for doctors not concerned in particular with the treatment of acute states. PMID- 2219770 TI - [The significance of rehabilitation in angiology]. AB - The author draws attention to the important position of different types of rehabilitation in the treatment of arterial, venous and lymphatic diseases. He mentions also different methodical procedures in the listed diseases. He emphasizes that rehabilitation, in particular intensive interval training, remains the main therapy of ischaemic disease of the lower extremities. PMID- 2219772 TI - [Prof. Julius Markovic, an outstanding patriot and physician]. PMID- 2219771 TI - [Use of nonparametric methods in medicine. I. Introduction]. AB - This is the introductory article of a series of eight where the authors discuss non-parametric methods. They compare the advantages and disadvantages of non parametric methods with parametric ones. Non-parametric methods can be used in particular where the investigated variables do not have a normal distribution, where the small size of the investigation and the type of classification do not permit to test, when information on the investigated variables are presented by means of rank or normal scales etc. Their disadvantage is a smaller ability to refute the null hypothesis, when it is not correct, as compared with parametric tests. PMID- 2219773 TI - [The problems of medical support in extreme situations]. PMID- 2219774 TI - [The organization of laboratory diagnosis in catastrophic medicine]. PMID- 2219775 TI - [The organization of a hospital at home for the Central Consultative Diagnosis Polyclinic]. PMID- 2219776 TI - [Experience with the integrated use of microcomputers in a military hospital]. PMID- 2219777 TI - [The prevention and treatment of stomatological diseases in servicemen: the problems and the reserves]. PMID- 2219778 TI - [Experience in treating patients with lesions of the periodontal tissues]. PMID- 2219779 TI - [The diagnosis and treatment of the vascular injuries in gunshot fractures of the leg bones]. PMID- 2219780 TI - [Military medical colleges on the pathways of perestroika]. PMID- 2219781 TI - [The treatment of the acute stage of inflammation of epithelial fistulae and cysts of the coccyx by using the CO2 laser]. PMID- 2219782 TI - [Surgical treatment in inflammation of epithelial fistulae and cysts of the sacrococcygeal region]. PMID- 2219783 TI - [The Paget-Schroetter syndrome]. PMID- 2219784 TI - [Current problems of rheumatic diseases (based on materials from an editorial round table)]. PMID- 2219785 TI - [The iridodiagnosis of diseases of the internal organs in persons with conjunctivitis]. PMID- 2219786 TI - [The epidemiology of AIDS (a review of the literature)]. PMID- 2219787 TI - [Experience in treating cutaneous leishmaniasis by using low-energy laser radiation]. PMID- 2219788 TI - [The psychophysiological characteristics of the occupational adaptation of servicemen]. PMID- 2219789 TI - [Ways to improve health education]. PMID- 2219790 TI - [The relationship of the arterial pressure level and blood lipids to body weight in flight personnel]. PMID- 2219791 TI - [The assessment of the functional state of the cardiorespiratory system in sailors with a high level of physical work capacity]. PMID- 2219792 TI - [The improved conservative treatment of pelvic bone fractures in multiple and combined injuries]. PMID- 2219793 TI - [A method for treating severe forms of typhoid peritonitis]. PMID- 2219794 TI - [The problems of building medical service personnel up to strength during World War II]. PMID- 2219795 TI - [A quarter century for the military medical faculties in medical institutes]. PMID- 2219796 TI - [The 50th anniversary of the Department of Military Naval and Hospital Therapy of the S. M. Kirov Military Medical Academy]. PMID- 2219797 TI - [Metabolic turnover of catecholamines in the heart of rats after nonfatal burns]. AB - The content and metabolic turnover of noradrenaline (NA) and adrenaline (A) have been studied in the hearts of rats subjected to nonlethal scalding. The results of the study have shown that in an early phase of the general reaction of the organism to thermal trauma it has come to the decreased NA content while in the later phase the NA content was in the limits of control values. The increased contents of Na and A in the murine hearts after monoamineoxidase inhibition and injection of L-DOPA indicated the preservation of the synthesis and overtaking of catecholamines by the heart muscle. The increase of the metabolic turnover and shortening of the time of the metabolic turnover of NA and A have pointed that the increased NA content in the hearts of the traumatized animals is the consequence of the increased requirements of these catecholamines by the heart muscle in the early posttraumatic phase. PMID- 2219798 TI - [Chlamydia trachomatis in women]. AB - The results of the prospective study of chlamydia trachomatis infection in women are presented. The study comprised 288 women aged from 19 to 67 years with the completed clinical and anamnestic data and the following tests have been performed: indirect immunofluorescence test for detection of Chlamydia trachomatis antigens in endocervical smears (using monoclonal antibodies), ELISA test for detection of IgG antibodies against Chlamydia trachomatis in the sera and complement binding reaction for detection of antibodies against grouped Chlamydia antigen. Chlamydia trachomatis infection was found in 29.51% of cases equally distributed in all age groups. The incidence of Chlamydia positive findings was analysed according to clinical diagnosis, parity, relevant data from gynecologic anamnesis and the results of vaginal secretion and Papanicolau's stain test. In order to establish a reliable diagnosis of Chlamydia trachomatis infection two methods should be regularly used: one direct-for detection of a causative agent in patients' materials, and the other-indirect, for detection of specific antibodies in the serum. PMID- 2219799 TI - [Injuries during specialist training of recruits]. AB - Traumatism of recruits has been studied during specialized infantry and artillery courses within the basic training of recruits. The prospective study refers to the application of the Plan and Program of Training and Education for 1985. It has been found that the observed activities did not present equally risky activities concerning traumatism of recruits of the studied branches of the army. Physical activity has shown to be the most risky one within the training program. PMID- 2219800 TI - [Verification of vital capacity and 1 second forced expiratory volume values in 14,234 candidates for aviation school]. AB - The values of vital capacity (VC), forced expiratory volume in the first second (FEV1) and Tiffeneau index (100xFEV1/VC) were determined in 14,234 examinees in the period 1977-1987. Examinations were performed using the Godart expirometer. After the statistical analysis of the results being performed, the unique table was made according to height and age of examinees. The examinees came from all regions of Yugoslavia. The results of the study can be used for establishment of standard values of pulmonary ventilation for candidates for aviation schools, i.e. for youngsters aging from 14 to 20 years. PMID- 2219801 TI - [Personal experience in the diagnosis and treatment of pulmonary embolism]. AB - The 188 patients with pulmonary embolism were treated at the Clinic for Pulmonary Diseases of the M.M.A. in the period 1979-1989. Clinical symptoms and signs, diagnostic procedures and therapy of pulmonary embolism are analysed. The diagnosis is difficult and is suggested by the predisposing factors, symptoms and signs of the disease as well as indirect diagnostic procedures. The contribution of perfusion lung scintigraphy is precious. Deep venous thrombosis of the lower extremities, the source of pulmonary embolism, is commonly clinically absent. The complete cure without complications was achieved in 156 (83%) patients. The most common complications were: early and late recurrences, hematuria and peptic bleeding. The lethal outcome occurred in two cases of basic disseminated malignant disease. PMID- 2219802 TI - [Value of the stress test in the evaluation of the severity of ischemic heart disease]. AB - Loading test was used in 156 patients with ischemic heart disease and the results of their selection are presented. In all patients occlusive coronary disease was detected by selective coronarography. They were divided in three groups. Two groups of patients had a high risk ischemic heart disease requiring surgical revascularization of the myocardium and selective coronarography. The first of these two groups comprised 48 patients with significant stenosis of the main tree of the coronary artery and the second comprised 35 patients with equivalent stenosis of this artery. The third group comprised 73 patients with ischemic heart disease of small risk in whom occlusive changes of the coronary arteries were of distal localization. The statistically significant difference was found between the two groups of patients with high risk and the third group with small risk according to early development of ST depression in the first minutes of loading, its degree, number of leads with ST depression, form and its maintenance after cessation of loading. The difference was also significant regarding the submaximal pulse rate and systolic blood pressure during loading test. It has been concluded that by using loading test as a functional diagnostic method patients with a high risk ischemic heart disease can be selected stressing the advantage of physiology over morphology. PMID- 2219804 TI - [Use of enamel-dentin adhesive in the restoration of defects in the cervico-root region of teeth]. AB - The incidence of cervical defects was epidemilogically studied on a sample of 60 teeth with periodonatl disease and cervical defects which were classified in three groups. Also, the control clinical prospective study comprised 44 esthetic external restorations made of monocomponent resin (Heliosit and Visio-Disperse) and bicomponent resin (Silar and Dentosit) in the cervico-radical region of the vestibular surface od teeth with periodontal disease. Enamel-dentin adhesive was used as a bonding agent. Two parameters were followed up: 1. restoration margin staining, and 2. retentional state of restoration. The studies have shown that: a) the cervico-radical defects affecting both the dentin-coronary third of the root and the dentin-cervical third of the crown were found in 64% of subjects with periodontal disease and cervical defects requiring application of monocomposite resin in the same percentage, b) enamel-dentin adhesive+ composite restorations made of monocomposite resin showed changes in both mentioned parameters in a significantly lower percentage being of markedly smaller intensity than those made of bicomposite resins, and c) bonding capacity of enamel-dentin adhesives is an important additional factor of retention of esthetic restorations made in the cervico-radial dental region. PMID- 2219803 TI - [Fibrin glue in tympanoplasty]. AB - In order to achieve more favourable anatomic and functionally more permanent position of the transmission materials, fibrin glue was applied in 68 patients undergoing different microsurgical interventions for the cure of inflammatory processes in the middle ear or improvement of conductive deafness of inflammatory or traumatic origin. Fibrin glue has shown to be equally suitable both in fixation of the biological materials - homografts and autografts and in fixation of alloplastic prostheses. The efficacy of preservation of the best position was demonstrated in all forms of direct collumelas, ossicular graft interposition, closure of the labyrinthine fistulas and reconstruction of the external attic wall. PMID- 2219805 TI - [Young people in the Yugoslav Military and smoking]. PMID- 2219806 TI - [Hypochondria--definition and clinical use of the concept]. PMID- 2219807 TI - [Treatment of late-stage skin porphyria]. PMID- 2219808 TI - [Advances in the surgical treatment of ostial stenosis of the left coronary artery]. PMID- 2219809 TI - [The action of a decimeter-wave electromagnetic field on the indices of the blood kallikrein-kinin system in rabbits with an experimental myocardial infarct]. AB - Continuous 10-day exposure of the heart and adrenal regions of rabbits with myocardial infarction to electromagnetic field produced by decimeter waves leads to activation of kallikrein-kinin system. With the heart exposure, this activation comes through marked changes in microcirculatory bed, whereas in the adrenal exposure it is trophic defects that are induced in the myocardium. The exposure of the thyroid regions brings about unnoticeable effect. PMID- 2219810 TI - [Physical factors in the treatment of patients with ankylosing spondylarthritis]. AB - The effect of decimeter electromagnetic waves, ultrasound, induction therapy, crysanol phonophoresis was compared in relevant treatment of 180 AS patients. The response to the above factors was almost similar in AS activity of the I degree. Central AS of the II degree of activity was more sensitive to decimeter waves while for peripheral and rhizomelic forms the results of crysonal phonophoresis were more positive. Dominating immunocorrective effect of the waves and partial immunodepressive action were referred to decimeter waves and crysanol phonophoresis, respectively. PMID- 2219811 TI - [Aspirin-butadione electrophoresis in the treatment of patients with rheumatoid arthritis]. PMID- 2219812 TI - [The balneological and traction therapy of osteoarthrosis patients]. PMID- 2219814 TI - [The use of UV irradiation to correct the immune system and decrease morbidity in athletes]. PMID- 2219813 TI - [A new heliotherapy unit for treating patients with osteoarthrosis deformans]. AB - The effectiveness of osteoarthritis deformans treatment was compared for impulse concentrated solar light and heliotherapy under screen gills. Either therapy was combined with therapeutic exercises, massage and mineral baths. PMID- 2219815 TI - [The interference-current therapy of chronic salpingo-oophoritis (a trial of studying the regional hemodynamics)]. AB - Blood redistribution in blood circulatory beds (the uterus, external genitalia and vagina) and as a whole have been established in exposure to interference currents. Ka index of rheoencephalography may be used as an additional objective criterion of individual sufficiency of physiotherapeutic exposure. PMID- 2219816 TI - [Experience with the combined treatment of chronic prostatitis]. AB - Available are the results of combined treatment of chronic prostatitis in 86 patients. The treatment schedule included ultraphonophoresis of highly dispersed drug mixtures, bitemporal UHF waves exposure, endourethral electrostimulation and laser radiation of prostatic tissue. The complex of interacting modalities has been substantiated pathogenetically. Clinical and laboratory assessment of the patients' response supports high effectiveness of the proposed combined schemes for management of chronic prostatitis. PMID- 2219817 TI - [The effect of electromagnetic oscillations in the decimeter range on the function of nerve and muscle tissues (experimental research)]. PMID- 2219818 TI - [The experimental effect of centimeter-range microwaves on drug biotransformation]. PMID- 2219819 TI - [A method for enhancing the therapeutic action of ultraviolet rays in psoriasis]. PMID- 2219821 TI - [Tumnin--the first place for radon treatment in the Far East]. PMID- 2219820 TI - [The differential use of methods of vibration therapy in the neurological manifestations of spinal osteochondrosis]. PMID- 2219823 TI - [The ecological problems of the health resort and recreational use of bodies of water]. PMID- 2219824 TI - [Physiotherapy during World War II]. PMID- 2219822 TI - [The experimental and clinical aspects of the action of electromagnetic fields on the endocrine glands and brain]. PMID- 2219825 TI - [Therapeutic physical exercise during World War II]. PMID- 2219826 TI - [The treatment of 5 multiple primary neoplasms in one patient over a period of 17 years]. PMID- 2219827 TI - [The local application of metronidazole during the radiotherapy of endometrial cancer]. PMID- 2219828 TI - [Morphologic criteria of the risk of cancer of the vulva]. PMID- 2219830 TI - [X-ray studies of Kaposi's sarcoma]. PMID- 2219829 TI - [Current approaches to the treatment of patients with lymphogranulomatosis]. PMID- 2219831 TI - [Paraneoplastic psychopathologic syndromes]. AB - The diagnosis of paraneoplastic neuro-psychic syndromes is very difficult and still remains an unresolved issue. A retrospective analysis included case histories of 79 patients with marked psychopathologic symptoms concomitant to cancer which had been verified at autopsy but had been difficult to diagnose during life. All these cases are regarded as having suffered paraneoplastic psychopathologic syndromes which are of great clinical and diagnostic interest. Certain theoretical observations concerning the pathogenetic mechanisms underlying paraneoplastic psychic disorders are made. PMID- 2219832 TI - [Melanoma of the skin: clinico-genetic studies]. AB - As a result of clinico-genealogical analysis of data on 691 skin melanoma patients, a classification of skin melanoma was elaborated which reflected the etiologic heterogeneity of the disease. Inheritable and non-inheritable forms of skin melanoma were identified. The inheritable tumor group included familial disease (2%) and tumors developing against the background of hereditary diseases and syndromes (32.7%). The data obtained served as basis for the identification of families with high genetic predisposition to skin melanoma development and for the assessment of individual risk of the disease in patients' relatives. PMID- 2219833 TI - [The diagnosis and treatment of primary malignant tumors of the sternum]. AB - Results of examination and treatment of 24 patients with primary neoplasms of the sternum including chondrosarcoma (18 cases), solitary plasmacytoma (5) and osteogenic sarcoma (1) were analysed. The diagnosis was based mainly on X-ray procedures and was further improved by computed tomography which allowed to precisely evaluate the extent of intrathoracic mass and its relation to adjacent mediastinal structures. Surgery was the main procedure used for the treatment of primary tumors of the sternum. Sixteen patients were operated on, and not a single case showed involvement of the mediastinum. Closure of defect was the major difficulty involved in the surgical treatment. Adequate resection of the sternum followed by autoplasty yielded good results. PMID- 2219834 TI - [Stimulation of the synthesis of C-reactive protein using pyrogenal in non neoplastic diseases and cancer of the lungs]. AB - Method of immunodiffusion titration of rabbit monospecific antiserum (The I. M. Mechnikov Central Research Institute of Vaccines and Sera of the USSR Ministry of Health) in agar was used to measure blood C-reactive protein (C-RP) level in patients with acute pneumonia (32), protracted pneumonia or activation of chronic non-specific lung pathology (101) and lung cancer (153) after a 3-4-week course of complex antiinflammatory treatment and a 10-14-day course of immunostimulation with pyrogenal (The N. F. Gamaleya Research Institute of Epidemiology and Microbiology). A decrease in the incidence (from 81.2% to 14.2%) and level (from 1.4 +/- 0.3 to 0.3 +/- 0.03 mg%) of C-RP was observed in cases of non-tumor pathology whereas in patients with lung cancer those values rose in step with tumor progression (from 72.2% and 0.4 +/- 0.07 mg% at stage I to 96.3% and 1.2 +/ 0.12 mg% at stage IV). Treatment with pyrogenal allowed to identify C-RP in patients with false-negative reaction in all subgroups. Two-week dynamic C-RP curves characterizing non-tumor and tumor pathology of the lung were plotted. PMID- 2219835 TI - [Melanomas of the anorectal region]. AB - Melanoma of the anorectal region is a rare disease which makes up 1.8% of all rectal malignancies and 1.4% of all cases of melanoma. Surgery is the only radical procedure for the treatment of anorectal melanoma. Abdomino-perineal extirpation of the rectum proved most radical. Overall five-year survival rate was 17.0 +/- 5.3%. PMID- 2219836 TI - [Immunologic markers of erythrocytes in lymphogranulomatosis]. AB - The paper summarizes results of a study on immunologic markers of eight erythrocytic systems (ABO, Rh-Hr, MNSs, Kell-Cellano, Daffy, Kidd, Levis and Diego) which include 21 antigens in healthy subjects and patients with Hodgkin's disease of the Armenian nationality. Peculiarities of distribution of some erythrocytic antigens in patients with Hodgkin's disease were identified. PMID- 2219837 TI - [Approaches to predicting the reaction of human tumors to radiotherapy]. AB - Immunofluorescent method using anti-thymidine antibodies was employed to assess proliferative activity of 217 human tumors including oropharyngeal, esophageal, gastric, rectal and lung cancer. The activity was evaluated before and, in 38 neoplasms, in the course of radiotherapy. It was shown that changes in the proliferative activity of oropharyngeal and gastric malignancies observed early in the course of radiation treatment may serve for predicting response. PMID- 2219838 TI - [The cytostatic action of the K+/H+ antiporter nigericin]. AB - A decrease in pH in Ehrlich ascites carcinoma cells to 6.3 leads to intracellular DNA synthesis inhibition. The inhibitory effect was achieved in the course of incubation of cells at pH 6.2 as well as by the addition of low-dose K+/H+ antiporter antibiotic nigericin. DNA synthesis inhibition by nigericin was not associated with significant decrease in ATP level or mitochondrial membrane potential. The effect was mediated by a decrease in intracellular pH rather than by a decrease in intracellular potassium level or elevation in that of intracellular sodium which accompanied nigericin treatment. PMID- 2219839 TI - [The antitumor effect of an extract of human umbilical cord]. AB - The study was concerned with the evaluation of effect of the extract of a human fetal organ, the umbilical cord, on development and growth of such transplantable tumors as Ehrlich's ascites tumor, sarcoma 37, sarcoma 180 and Zajdela's hepatoma as well as of dimethylbenzanthracene- and benzo(a)pyrene-induced cancer. In a subgroup of animals who had been vaccinated once or twice prior to inoculation of cells, a significant inhibition of growth of tumors of all the histologies except sarcoma 180 was observed alongside with a decrease in tumor incidence and partial resorption of ascitic fluid. Preliminary vaccination of rats interfered with dimethylbenzanthracene- and benzo(a)pyrene-induced carcinogenesis reducing tumor incidence and assuring longer latent period and slower progression of cancer. PMID- 2219840 TI - [Organizational principles of the outpatient examination of patients suspected of malignant tumors]. AB - Out-patient diagnosis of cancer is carried out in three stages which involve activities of different physicians. Cancer is first suspected by a general practitioner. Prophylactic measures other than examination by specialists and chest photo-roentgenography proved insufficient, and the authors give reasons for this. During the second stage, the patient undergoes further thorough examination which should be well organized to succeed. The third stage, viz. making the final diagnosis, should be performed in an oncologic establishment only. PMID- 2219841 TI - [The attitude of cancer patients to their own diagnosis]. AB - The wide spectrum of viewpoints on how fully should a cancer patient be informed of his or her disease made it interesting to evaluate patients' own attitude to the issue. A questionnaire was offered to 280 cancer patients to assess the degree of awareness of their disease as well as psychologic preparedness to face the true diagnosis. As many as 93.6% of patients expressed a certain degree of desire to know diagnosis and details of their disease. PMID- 2219843 TI - [Echographic semiotics of cancer of the breast]. AB - Analysis of ultrasonic tomograms of 228 cases of breast cancer identified three ultrasonographic patterns of tumor which included seven basic variants. Ultrasonographic features of tumor were compared to their histology. Methods of ultrasonic examination of the breast and processing data are described. PMID- 2219842 TI - [The combination treatment of malignant bone tumors using fast neutrons]. AB - The study deals with results of a clinical trial evaluating treatment efficacy of a 6 MeV neutron beam produced by Y-120 cyclotron (Kiev). Procedures of preoperative radiotherapy and radical treatment are discussed. Radiotherapy was administered to 52 patients suffering chondrosarcoma (30 cases), osteogenic sarcoma (15) or chordoma (7). Combined treatment (radiation + surgery) was given to 22 patients whereas neutron beam therapy--to 30. All patients with osteogenic sarcoma received adjuvant combination chemotherapy. Three-year survival rate was compared to that observed in controls in whom combined treatment had included gamma-therapy. A significant increase in three-year survival rate was observed for osteogenic sarcoma and chordoma whereas for chondrosarcoma the improvement in survival proved insignificant. The use of fast neutrons in combined treatment of bone tumors was considered promising. PMID- 2219844 TI - [The ambulatory care of patients with precancerous diseases of the stomach]. AB - Two hundred and ninety-four patients with precancerous lesions of the stomach were followed and treated. The group included cases of gastric ulcer (101), polyps (78), atrophic-hyperplastic gastritis (81) and 34 patients who had undergone gastric resection for duodenal ulcer. Pathologic foci were surrounded by areas of epithelial dysplasia of varying degree in almost all patients. In the course of follow-up and treatment, dysplasia regressed in several cases and progressed to early cancer of the stomach in three. Recommendations for periodicity of check-ups of patients with chronic cancer of the stomach depending on degree of mucosal epithelium dysplasia were developed. PMID- 2219845 TI - [The relation between dysplasia of the bronchial epithelium and endocrine shifts in patients with chronic nonspecific diseases of the lungs]. PMID- 2219846 TI - [The human immunodeficiency virus type 2]. PMID- 2219847 TI - [Experimental research on the ecology of the tick-borne encephalitis virus]. PMID- 2219848 TI - [The prodigiozan and pyrogenal stimulation of the humoral response to influenza virus antigens in mice]. AB - The adjuvant properties of prodigiosan and pyrogenal, lipopolysaccharides of medical importance, were studied. Prodigiosan inoculated to mice together with influenza virus was found, on the one hand, to increase 10-fold the titer of specific antibodies and, on the other, to allow to reduce the antigen dose 50 fold or more. No adjuvant properties of pyrogenal were observed under the experimental conditions. PMID- 2219850 TI - [The importance of early and maternal antibodies to HBsAg in preventing hepatitis B in plasma recipients]. AB - Among 182 prematurely born babies receiving transfusions of HBsAg-negative plasma (blood), 49 (26.9%) were found to have antibodies to HBsAg (anti-HBs) in the 1st week of life, of them 29 had maternal and 20 early antibodies. Early anti-HBs and maternal antibodies detectable in blood sera of premature newborns were found to be protective, capable of preventing both icteric forms of acute posttransfusion hepatitis B and anicteric variants of this infection after plasma transfusion. PMID- 2219849 TI - [The immunomodulating action of mytilan in an experimental influenza infection]. AB - The materials characterizing the immunomodulating activity of mytilan, a bioglycane from an industrial object of Japanese sea, Crenomytilus grayanus, in experimental influenza infection are presented. The preparation protected up to 60% of mice intranasally inoculated with influenza virus, and significantly inhibited influenza virus reproduction. It induced interferon (possibly gamma IF) synthesis in low titres. The immunomodulating effect of mytilan consisted in stimulation of specific antibody genesis, enhancement of chemotaxis, increasing oxidation-reduction activity, enhancement of expression of Fc gamma-receptors by splenocytes and macrophages, enhancement of antibody-dependent spleen cell cytotoxicity, increased activity of natural killer cells, as well as increased complementary activity of blood serum and enhanced expression of C3 receptors by mouse spleen cells. PMID- 2219852 TI - [The characteristics of the interaction of the proteins comprising the virions of the human immunodeficiency virus type 1]. AB - Treatment of virions of human immunodeficiency virus type 1 (HIV-1) with ionic and nonionic detergents (NP-40, octylglucoside, sodium deoxycholate) exerted an effect on the virus uncommon for enveloped viruses: instead of solubilization, both glycoproteins (gp120 and gp41) were found in subviral particles, whereas the core protein p24 was found in the supernatant fluid after the removal of subviral particles by centrifugation. The matrix protein p17 and unprocessed molecules of the precursor protein p55 were associated with subviral particles. The above data confirm the proposed model of the HIV-I structural organization according to which glycoproteins are incorporated into the isometric matrix formed by protein p17. Our data indicate that the core protein p24 is not incorporated into the matrix and not associated with nucleocapsid proteins. PMID- 2219851 TI - [The localization of delta antigen in the hepatocytes in chronic delta hepatitis]. AB - The results of immunohistochemical and electron microscopic examinations of liver biopsies from 47 patients with chronic delta hepatitis are presented. Delta antigen (HDAg) was detected by immunoperoxidase method in the liver of 35 (74.4%) patients. HDAg was demonstrated in hepatocyte nucleus alone in 22 (62.9%) patients, simultaneously in the nucleus and the cytoplasm in 9 (25.7%), in the cytoplasm alone in 4 (11.4%). In nuclear localization, delta antigen may fill the entire nucleoplasm or only the peripheral zone of the nucleus. When delta antigen fills the entire nucleus, hepatocytes undergo more marked pathological changes than those in which HDAg is localized in the nuclear periphery or those where no delta antigen was found. PMID- 2219853 TI - [The properties of HIV protease synthesized in E. coli cells]. AB - A hybrid plasmid pPR6 was constructed containing BgII-EcoRI fragment of the pol region of HIV (strain IIIB) genome which determined the synthesis of virus specific protease. Extracts of E. coli DN5/pPR6 bacteria provided for specific hydrolysis of hybrid protein p165 (the N-terminus of which is presented by complete beta-galactosidase and the C-terminus by duplicated area of virus specific precursor p55 containing a site for virus-specific protease located at the border of proteins p17 and p24) with formation of products having molecular weights of 19, 42, 28, 23, and 19 kD. Polypeptides 119K, 23K, and 19K are products of complete hydrolysis, and 42K a result of partial cleavage. The kinetics of hydrolysis in relation to pH values of the reaction mixture was analysed. It is suggested that the reported system of HIV protease activity determination be used for screening of potential inhibitors of this enzyme. PMID- 2219854 TI - [A mixed infection of lymphoid cell lines by the human T-lymphotropic retrovirus type I (HTLV-I) and the measles vaccine virus]. AB - Interaction of HTLV-1 and vaccine strain of measles virus (VM-L16) in different T and B cell lines was studied. VM-L16 replicated in T and B cells with a cytopathic effect. At a multiplicity of infection of 1 TCD50 per 10 cells, all the cells in cultures died within 4-13 days. No effect of HTLV-1 on cell sensitivity to VM-L16 was demonstrated. HTLV-1 produced in various T-cell lines had different syncytium-forming activity in XC cell cultures. Cocultivation of C91/pL cells with XC cells led to the formation of multiple syncytia. HUT-102 cells had no such activity. Infection of these cell lines with VM-L16 did not change their properties. Another HTLV-1-infected cell line, MT-2, caused insignificant aggregation of XC cells. Infection of the latter with VM-L16 increased the number of racemations 8-fold, and they consisted of numerous adhesive cells. The cell adhesion, however, which is the first stage of syncytium formation did nor terminate in cytoplasm confluence. MT-2 nad XC cell lines may be used as model systems for the study of various factors influencing HTLV-1 activation. PMID- 2219855 TI - [The purification of tick-borne encephalitis virus preparations of cellular DNA]. AB - According to the WHO requirements, the concentration of cellular DNA in vaccine preparations produced by pooling virus from continuous cell lines is limited to 100 ng/dose. In this study, different methods were used for purification of tick borne encephalitis virus suspensions grown in continuous cultures of cell line 4647 from cellular DNA. Two approaches are proposed based on treatment with DNAse and promamin sulfate which allow one to reduce cellular DNA concentration in the virus preparation to the acceptable level. Prospects of their use in vaccine production are discussed. PMID- 2219856 TI - [The immunogenic and hemagglutinating activities of tick-borne encephalitis viral strains isolated from patients in different parts of the geographic range of the disease]. AB - Considerable variability of the immunogenic and antigenic (in HA test) activity of tick-borne encephalitis virus strains was shown. No correlation was observed between the hemagglutinating activity of strains and their capacity to stimulate humoral immunity in the infected animals. The results of the study did not allow one to place strains into groups according to the area of isolation in relation to their immunogenic and antigenic activity. PMID- 2219857 TI - [Cellular transformation in an MDCK culture caused by the agent of amyotrophic leukospongiosis]. AB - The possibility of infecting epithelioid MDCK cell culture with the agent of amyotrophic leukospongiosis (AL) was shown. Various morphofunctional changes were observed in the infected cells. In the first subpassage, the saturation density and yields of cells increased, while their mitotic activity decreased and adhesive properties changed. In the second subpassage, the cell morphology and monolayer architectonics changed, the cells losing the ability to form a confluent monolayer. The infected cultures died in further subpassages. Clinical signs of the disease and morphological changes in the CNS typical of AL were observed in the animals infected with a homogenate of cells and culture fluid from the AL-agent-infected cultures. PMID- 2219858 TI - [The antiviral efficacy of ribamidil in an experimental infection of animals with the Venezuelan equine encephalomyelitis virus]. AB - Considerable differences in antiviral efficacy of ribamydil were demonstrated in various animals experimentally infected with Venezuelan equine encephalomyelitis virus. The infection in baboons was quite similar to the manifestations of this disease in man as reported in the literature. With ribamydil used prophylactically, manifestations of the infection in monkeys were less marked. PMID- 2219860 TI - [The comparative characteristics of the genetic traits of the Lassa and Mopeia viruses]. PMID- 2219859 TI - [The determination of viral antibodies in patients with disseminated sclerosis]. PMID- 2219861 TI - [The preservation of human immunodeficiency viruses by lyophilization]. PMID- 2219863 TI - [An evaluation of immunoenzyme test systems for detecting HIV antibodies in an international trial]. PMID- 2219862 TI - [The detection of the HIV antigen and antibodies by using an agglutination test with Soviet latex]. PMID- 2219864 TI - [A comparative evaluation of methods for detecting the Rift Valley fever virus]. PMID- 2219866 TI - [A list of the scientific topics recommended by the Expert Council to the Presidium of the Academy of Medical Sciences of the USSR on the scientific problems of AIDS for study in 1989-1990]. PMID- 2219865 TI - [The trans-activator genes of viral transcription]. PMID- 2219867 TI - [A list of the scientific topics recommended by the Expert Council to the Presidium of the Academy of Medical Sciences of the USSR on the scientific problems of AIDS for study in 1989-90]. PMID- 2219869 TI - The changing epidemiology of diabetes mellitus among Navajo Indians. AB - Although early descriptions of diabetes mellitus among Navajo Indians characterized the disease as an infrequent and "benign chemical abnormality," the prevalence of diabetes and its complications among Navajos appears to have increased substantially in this century. We reviewed recent Indian Health Service inpatient and ambulatory care data and compared these data with previous reports. Of the estimated Navajo population aged 45 years or older, 4,331 (16.9%) had an ambulatory care visit for diabetes between October 1, 1986, and September 30, 1987. Diabetes was coded for 1,041 (7.0%) of hospital admissions of persons aged 20 and older. Of 377 lower-extremity amputations done from 1978 to 1987, diabetes was involved in 245 (66%). The 1986 age-adjusted mortality rate from diabetes was 30.3 per 100,000, approximately twice that for the general US population. The explanation for the increased prevalence of diabetes mellitus among Navajos probably relates to an increasing prevalence of obesity. PMID- 2219868 TI - Compliance and outcome in anorexia nervosa. AB - Anorexia nervosa is notoriously difficult to treat, but little is known regarding the relationship of compliance to treatment outcome. We investigated in 41 adolescents who fulfilled DSM-III-R criteria for anorexia nervosa, the relationship between the completion of a standard psychosocial treatment program, subtypes of anorexia nervosa, and outcome as determined by standardized measurements. These adolescents were observed for an average of 32.4 months. Overall, 29 patients (70%) improved considerably, but 10 (24%) were symptomatic, and 2 (5%) remained in poor condition. There were no deaths. Of the 41 patients, 14 (34%) completed our entire treatment program, 15 (37%) received major treatment and failed in the outpatient follow-up phase only, 7 (17%) dropped out of inpatient treatment before its completion, and 5 (12%) refused treatment in our system altogether. Of all the dropouts, 10 received no further treatment. One patient was admitted to hospital elsewhere but again dropped out in the outpatient phase of that program. Seven patients (17%) received further outpatient treatment only, and 9 (22%) received inpatient and outpatient care and seemingly completed their treatment. Treatment completion significantly affected the measures of global clinical functioning and specific psychopathologic features, but only for those patients who completed the initial program. Bulimic patients did considerably worse on follow-up and were less likely to complete treatment. Patients with restricted anorexia nervosa were more likely to complete treatment than those with a bulimic subtype (P = .03). Differential compliance rates in the two subtypes confound the effects of treatment completion and need to be controlled for in future studies. Depression was not associated with noncompliance but, if present, was associated with poor outcome on follow-up and abated in only a third of those in whom it was initially present. PMID- 2219870 TI - Neurologic complications of cardiac transplantation. AB - Between 1984 and 1989, orthotopic cardiac transplantations were done in 90 patients from 10 to 65 years of age for end-stage, refractory congestive cardiomyopathy. Two patients had had ischemic strokes 5 months and 18 years, respectively, before transplantation. Six patients (7%) suffered acute neurologic events perioperatively. Three patients suffered cerebral infarctions. In 1 case this occurred 10 days before transplantation--probably as a result of systemic hypoperfusion--with the placement of ventricular assist devices. Two others suffered infarctions 5 and 21 days, respectively, after transplantation, each of probable embolic origin. Two patients had an acute intracerebral hemorrhage 21 and 36 days, respectively, after transplantation; both were located within the basal ganglia and subcortical regions. Both patients had moderate to severe hypertension, and in 1, renal failure and a coagulopathy developed before hemorrhage. Tremor, seizures, and an altered level of consciousness developed in 1 patient as an apparent toxic reaction to cyclosporine treatment. Only 1 patient died as a result of the neurologic complication--of an acute intracerebral hemorrhage. Three patients recovered fully, 2 partially. Only the case of drug toxicity could be directly attributed to the transplantation procedure itself. We conclude that the risk of an acute neurologic insult with orthotopic cardiac transplantation is low but may result from drug toxicity, cerebral ischemia, or hemorrhagic mechanisms. PMID- 2219871 TI - Alcohol and trauma. An endemic syndrome. AB - Injuries are a pervasive and costly problem, and alcohol use appears to be an important risk factor for injury. We examined the blood alcohol levels and selected demographic and epidemiologic variables recorded on trauma patients by 1 trauma center for a 28-month period. A total of 2,262 trauma patients were admitted to the trauma center during this period, of whom 75% were male and 72% were injured in vehicle-related incidents. Blood alcohol levels of 2,095 patients (93%) were measured, and alcohol was present in the blood of 855 (41%). Of those patients with a blood alcohol level done, 32% had a level higher than 100 mg per dl. We conclude that the level of alcohol involvement in trauma is high and that this involvement must be addressed by the medical community and the health care system. PMID- 2219873 TI - Selenium. Nutritional, toxicologic, and clinical aspects. AB - Despite the recent findings of environmental contamination, selenium toxicosis in humans is exceedingly rare in the United States, with the few known cases resulting from industrial accidents and an episode involving the ingestion of superpotent selenium supplements. Chronic selenosis is essentially unheard of in this country because of the typical diversity of the American diet. Nonetheless, because of the growing public interest in selenium as a dietary supplement and the occurrence of environmental selenium contamination, medical practitioners should be familiar with the nutritional, toxicologic, and clinical aspects of this trace element. PMID- 2219872 TI - From Leningrad to the day-care center. The ubiquitous Giardia lamblia. AB - Giardiasis is recognized as a worldwide public health problem. Seroprevalence data from both the developing and developed world show high rates of carriage in populations at risk for fecal-oral transmission, such as children in day-care centers. Outbreak investigation has expanded our understanding of reservoirs for Giardia lamblia and of the routes of transmission. Various host factors have been associated with infection. The pathogenesis of giardial infections is being elucidated, in particular the role of lectin activation in producing disease. Three standard chemotherapeutic agents are available in the United States. The institution of community-wide prevention measures is equally important. Current areas of investigation including antigenic composition and enzymatic variants should result in effective forms of immunotherapy, while more effective forms of chemoprophylaxis could assist in eradicating the pathogen from institutional settings. PMID- 2219876 TI - Recent developments in radial keratotomy. AB - The Scientific Board of the California Medical Association presents the following inventory of items of progress in ophthalmology. 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, research workers, or scholars to stay abreast of these items of progress in ophthalmology 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 Ophthalmology of the California Medical Association, and the summaries were prepared under its direction. PMID- 2219877 TI - Current uses of collagen shields. PMID- 2219874 TI - Prostaglandins, the kidney, and hypertension. AB - Prostaglandins are part of the family of oxygenated metabolites of arachidonic acid known collectively as eicosanoids. While they are formed, act, and are inactivated locally and rarely circulate in plasma, they can affect blood flow in some tissues and so might contribute to the control of peripheral vascular resistance. Few studies have shown any derangement of total body prostaglandin synthesis or metabolism in hypertension, but increased renal synthesis of one prostanoid, thromboxane A2, has been noted in spontaneously hypertensive rats and some hypertensive humans. This potent vasoconstrictor may account for the increased renal vascular resistance and suppressed plasma renin activity seen in many patients with hypertension. Increased renal vascular resistance could increase the blood pressure directly as a component of total peripheral resistance or indirectly by increasing glomerular filtration fraction and tubular sodium reabsorption. Specific thromboxane synthesis inhibitors not only decrease renal thromboxane production but also increase renal vasodilator prostaglandin synthesis when prostaglandin synthesis is stimulated. This redirection of renal prostaglandin synthesis toward prostacyclin might be of benefit in correcting a fundamental renal defect in patients with hypertension. PMID- 2219875 TI - Stress and hypertension. AB - In susceptible persons emotional stress results in immediate sympathetic stimulation, with a vasomotor response that results in a high-output state and elevated blood pressure; the vasopressor response seems to be transient. There seems to be no longitudinal epidemiologic validation of the attractive hypothesis that transiently elevated blood pressures are the prelude to fixed hypertension, however. The acquisition of hypertension by populations abandoning their traditional mode of living has been attributed to the sociocultural stress inherent in westernization, but these studies usually have not taken into account concomitants of this type of acculturation, such as dietary changes and increased body weight. The inverse relationship of blood pressure levels to education could explain the development of hypertension when aspiration to upward mobility is thwarted. The severity of perceived occupational stress relates inversely to blood pressure, suggesting that familiarity with a job renders the demands made by the work environment more predictable and less threatening in terms of vasopressor response. PMID- 2219879 TI - Evaluating functional vision. PMID- 2219878 TI - Botulinum toxin for the treatment of blepharospasm and strabismus. PMID- 2219880 TI - Extended-wear soft contact lenses. PMID- 2219881 TI - Update on retinopathy of prematurity. PMID- 2219882 TI - Current recommendations for the treatment of diabetic eye disease. PMID- 2219883 TI - Using fluorouracil in surgical therapy for glaucoma. PMID- 2219884 TI - The dilemma of neonatal ophthalmic prophylaxis. PMID- 2219885 TI - Growing interest in selenium. PMID- 2219886 TI - Lung abscess causing Horner's syndrome. PMID- 2219887 TI - Transient infantile hypertension. PMID- 2219888 TI - Valproic acid-associated encephalopathy. PMID- 2219889 TI - Regulation of immunity by anti-T-cell antibodies. AB - Current pharmacologic approaches to immune suppression leave much to be desired. The prevention of allograft rejection and the suppression of autoimmunity generally require treatment with corticosteroids or cytotoxic drugs, or both, which may not be sufficiently effective and which frequently cause serious immediate and long-term complications. With the advent of monoclonal antibody technology, it has become possible to identify and selectively inhibit distinct elements in the immune system that contribute to pathologic immune responses. This achievement has led to new therapeutic strategies that may be safer and more effective than the immunosuppressive therapies currently available. Many of these strategies focus on subsets of T cells because of the critical importance of T cells in immune responses. Monoclonal antibodies directed against CD4 + T cells, T-cell activation antigens, and T-cell receptor families have all shown promise in animal models and, in some cases, in preliminary human trials. The challenge now is to translate this promise into practical new forms of immunosuppressive therapy. PMID- 2219891 TI - Pleuropulmonary manifestations of hepatic amebiasis. AB - Pleuropulmonary manifestations of hepatic amebiasis occurred in 30 patients; 18 (60%) presented with at least 1 pulmonary complaint and 10 (33%) had multiple pulmonary symptoms. In 14 patients (47%), abnormalities were found on examination of the chest. In 16 chest roentgenograms (53%), there was at least 1 abnormality: right-sided pleural effusion (9 patients) and elevated right hemidiaphragm (8 patients) were the most common. All patients were treated with metronidazole (Flagyl) and had resolution of the amebic liver abscess and pulmonary disease. Pleuropulmonary disease is a common complication of amebic liver abscess. The clinical presentation and chest roentgenograms are virtually diagnostic and obviate the need for invasive procedures to confirm the diagnosis. Pleuropulmonary disease resolves with amebicidal treatment of the hepatic abscess. PMID- 2219890 TI - Tryptophan-induced eosinophilia-myalgia syndrome. AB - Eight patients who became ill while taking tryptophan had myalgia, fatigue, rash, fever, edema, alopecia, arthralgias, diminished joint motion, skin tightening, muscle cramping, and distal paresthesias. Three had shortness of breath, and one had pulmonary hypertension. Laboratory abnormalities included peripheral eosinophilia, leukocytosis, thrombocytosis, raised erythrocyte sedimentation rate, and elevated serum levels of aldolase, lactate dehydrogenase, and liver enzymes. Of 4 chest radiographs, 3 were abnormal. Of 5 skin and muscle biopsies, 4 showed sclerosis or mixed inflammatory cell infiltration of the dermis, subcutis, and fascia. Eosinophils were often present, but vasculitis was absent. Muscle inflammation was minimal. We conclude that the "eosinophilia-myalgia syndrome" is related to the ingestion of tryptophan and that abnormalities in the secretion of lymphokines may be important in its pathogenesis. PMID- 2219893 TI - Does paramedic-base hospital contact result in beneficial deviations from standard prehospital protocols? AB - We reviewed written and audio records of paramedic-base hospital radio contact to determine whether care differed from that suggested in standard prehospital care protocols. Records of all 659 contacts for seizure, syncope, abdominal pain, or altered mental state during 1987 (28.4% of all contacts) were scored for the use of standard therapies (such as intravenous access, oxygen, naloxone hydrochloride) and unanticipated therapies (intubation, nitroglycerin). Cases that involved unanticipated treatments were reviewed to determine whether they could have been prospectively identified by simple clinical findings. Standard therapies were used in the majority of patients. Unanticipated therapies were administered to 13 patients, all of whom had abnormal vital signs, diaphoresis, respiratory distress, or a second prominent symptom. Data suggest that protocols could replace radio contact for most patients and that the few who might benefit from radio contact can be easily identified. A 90% reduction in radio contacts in Los Angeles county could save $3 million each year. PMID- 2219892 TI - Barriers to prescribing the Copper T 380A intrauterine device by physicians. AB - From a questionnaire sent to all obstetricians and gynecologists and all family and general practitioners in San Diego County, California, regarding the Copper T 380A intrauterine device, substantial barriers to prescribing it were identified. Of all physicians responding, 40% reported that they were not recommending the Copper T 380A to anyone, the single most common reason given being concern about medical liability. A lack of knowledge about the new device, a lack of intrauterine device insertion skills, and certain medical practice settings were also important barriers to prescribing it. The new intrauterine device is considered in the context of innovation-diffusion theory. Substantial amounts of education and training and improvement in the medical-legal climate are needed before current barriers to prescribing the new device are removed. PMID- 2219896 TI - Failure to recognize late postpneumonectomy empyema. Role of diagnostic thoracentesis. PMID- 2219894 TI - Therapeutic cardiac catheterization in children. AB - Cardiac catheterization, once the mainstay of diagnosis in children with congenital heart disease, has become a therapeutic modality for many conditions. Balloon dilatation can now open stenotic valves and vessels, coils and umbrellas can now close unwanted communications, and emboli can be withdrawn without surgical intervention. PMID- 2219897 TI - Pericarditis--an extraintestinal complication of inflammatory bowel disease. PMID- 2219895 TI - Overview of hemochromatosis. AB - Hemochromatosis is an autosomal recessive genetic disorder that occurs with high prevalence in populations of European origin. The gene that is abnormal in hemochromatosis is found on the short arm of chromosome 6 in close proximity (approximately 1 centimorgan) to HLA-A, but the product coded for by that gene is unknown. The pathogenetic mechanism in hemochromatosis is that of continued, excessive absorption of dietary iron with loss of normal control mechanisms, leading to a gradual but vast expansion of storage iron as ferritin and especially as hemosiderin. Through mechanisms that probably include peroxidation of lipid membranes, the excess iron injures hepatocytes, islet B cells, gonadotropes in the anterior pituitary, myocardium, synovial cells, and chondrocytes, and probably other cells and tissues as well. Most patients with hemochromatosis remain undiagnosed throughout life. Removal of the excess iron by phlebotomy will prevent all of the complications of hemochromatosis when begun early and will significantly improve survival in virtually all patients. It is important, therefore, that the diagnosis of hemochromatosis be considered much more frequently in clinical medicine in order that this effective therapy be utilized. PMID- 2219898 TI - Rattlesnake capsule-induced Salmonella arizonae bacteremia. PMID- 2219899 TI - Indolent Staphylococcus aureus pneumonia. PMID- 2219900 TI - Ride and tie. A hybrid sport with synergistic potential for injury. PMID- 2219901 TI - The eosinophilia-myalgia syndrome. PMID- 2219902 TI - Hemochromatosis--treatment is easy, diagnosis hard. PMID- 2219903 TI - Transcatheter treatment of congenital heart disease. Past, present, and future. PMID- 2219904 TI - Human growth hormone--orphan with a silver spoon. PMID- 2219905 TI - Family physicians and obstetrics. PMID- 2219906 TI - Just say no? PMID- 2219907 TI - Physician diversion programs and AA. PMID- 2219908 TI - There ought to be a law. PMID- 2219909 TI - Dying of a broken heart. PMID- 2219910 TI - [Arrhythmias during automobile driving in patients after acute myocardial infarction]. AB - In 90 patients after acute whole-thickness myocardial infarction suffered 3-48 months earlier 24-hour ECG recording was done for assessment of arrhythmias occurring while they were driving cars and for their comparison with the remaining recording hours. In most patients driving cars episodes of sinus tachycardia even up to 130/min were noted, in about half the patients some increase occurred in the frequency of ventricular ectopic beats, in two patients double and in one patient triple ectopic beats (salvoes) appeared, although they had not been recorded when the patients were not driving cars. The study was carried out (and is still continued) in autumn-winter, when the conditions of car driving were worse. None of the patients was in a collision-threatening situation which could increase dangerous arrhythmias. PMID- 2219911 TI - [Effect of nitrates on left ventricular function and exercise tolerance in patients with mild circulatory failure caused by ischemic heart disease]. AB - In 26 patients with ischaemic heart disease with symptoms of mild chronic circulatory failure (NYHA grade II) aged 56.2 +/- 14.4 years the left ventricular function was tested by two-dimensional echocardiography, the exercise tolerance was determined on cycle ergometer at submaximal workloads, the cardiothoracic index (CTI) and cardiac volume index (CVI) were calculated from chest radiograms. The tests were done before and after 2 and 6 weeks of treatment with isosorbide dinitrate in doses of 49.6 +/- 15.2 mg/day. Isosorbide was found to increase somewhat the ejection fraction (EF), and to raise statistically significantly (p less than 0.05) the velocity of shortening of the circumferential fibres in left ventricular myocardium (mVCF), and to reduce the internal dimensions of the left ventricle (LVIDd and LVIDs), without changing the values of the ejection index (SVI) and cardiac index (CI). Decreased transverse dimensions of the left ventricle was correlated with a significant decrease of the CVI index. No statistically significant effect of isosorbide was noted on the parameters characterizing exercise tolerance but the quotient of the exercise-induced heart rate by the workload (HR/Wat) and the index of myocardial oxygen requirement (HRx Ps) were decreased in a demonstrable way. PMID- 2219912 TI - [Blood and plasma viscosity and the distance of intermittent claudication in patients with type II diabetes and thrombophlebitis]. AB - In 49 patients with insulin-resistant diabetes, with ischaemia of the lower extremities blood viscosity was measured at low coagulation rates and plasma viscosity was determined also. Moreover plasma measurements were done of total lipids, alpha-, pre-beta-, and beta lipoproteins, triglycerides, total cholesterol, free fatty acids, and, besides that, the hematocrit was measured. Immediately after blood sampling for rheological and biochemical investigations the distance of intermittent claudication was measured. A rather considerable increase of blood and plasma viscosity was noted in the patients in comparison with controls, other findings included disturbances of lipid metabolism, increased fibrinogen level, and a negative correlation between the distance of intermittent claudication and blood and plasma viscosity. PMID- 2219914 TI - [Esophageal achalasia in children (analysis of five cases)]. AB - Oesophageal achalasia is a disease of middle age and is only exceptionally observed in children. Five patients aged from 6.5 to 14 years were treated for this achalasia. Routine therapeutic method was repeated pneumatic dilatation of the cardia with a Rider-Moeller dilator. In all, 33 such procedures were carried out without complications. Very good results were obtained in 2 cases already after 3 dilatation procedures. The remaining 3 cases required surgical intervention: in 2 of them esophagomyotomy with antireflux operation was done with a very good result in one case and a good result in another case. The child not treated surgically (lack of parental consent) has still most signs of achalasia with body weight below the 3 centile and with recurrent respiratory infections. The follow-up is from 5 to 66 months. PMID- 2219913 TI - [Comparison of the quantitative determination of blood in stools with the Hemoccult test in various digestive tract diseases]. AB - The reported investigations of haemoglobin (Hb) concentration in stools of healthy subjects and patients with digestive tract diseases were carried out for determining the physiological value of blood loss into the digestive tract, and for comparing the sensitivity of quantitative and qualitative tests for demonstration of occult blood in stools in cases of colonic neoplasms. The qualitative Haemoccult test was compared to the quantitative test based on heme conversion to porphyrins by iron decoupling, which makes possible determination of total Hb content in stools and measurement of the so called intestinal fraction which develops as a result of Hb conversion to porphyrins in the upper digestive tract. PMID- 2219915 TI - [Urapidil (Ebrantil) use in patients on chronic hemodialysis]. AB - In 10 patients on chronic haemodialysis treatment for terminal renal failure with hypertension urapidil (Ebrantil) was given in one daily dose of 30 mg, usually continuing the previously used antihypertensive drugs. A significant decrease of the systolic and diastolic arterial blood pressure was achieved in most cases. Full therapeutic effect was manifested after several weeks of drug administration. During the treatment no tendency was noted for orthostatic hypotension, and no other side effects were observed. It seems that urapidil may be useful in the treatment of hypertension in dialysed patients. The usefulness of the drug in monotherapy requires further studies. PMID- 2219917 TI - [Markers of osteoporosis in clinical practice]. AB - For the assessment of the degree of osteoporosis progression of use are, besides biochemical and histological investigations, also photodensitometry, microradiography and radiological examinations. The last of them are easily available and cheap and they are recommended for screening examinations. Using the cortico-diaphyseal index determined by an own method and the Singh index it was found that atrophy of the spongy bone is not parallel in conditions regarded as pathological. The simultaneous use of both indices makes possible an easy, simple and rapid assessment of the degree of bone atrophy providing a possibility of introducing prophylactic and therapeutic management. PMID- 2219916 TI - [Ultrasonographic assessment of changes in the location of the lower border (termed migration) of the placenta]. AB - Ultrasonographic assessment of the so called placental migration was done in 136 patients in whom the preliminary diagnosis was made between 18th and 34th week of pregnancy. It was found that placental migration was a commonly observed phenomenon in patients with preliminary diagnosis of low-located marginal placenta previa while in the case of central placenta previa it occurred sporadically only in the second trimester of pregnancy. The lower placental border migration rate was higher in the second than in the third trimester of pregnancy. PMID- 2219918 TI - [Is local antiproteolytic failure the cause of a prolonged course in various forms of glomerulonephritis?]. AB - Just as in other inflammatory processes in glomerulonephritis also a great role has been ascribed recently to proteases released from phagocytes and mesangial cells. On the basis of original observation (clinical and experimental) of glomerulopathy inhibition by EACA, the authors present the concept of local antiproteolytic failure as the cause of protracted course of certain forms of glomerulonephritis. PMID- 2219919 TI - [Endogenous growth factors]. PMID- 2219920 TI - [Advances in the diagnosis of Alzheimer's disease]. AB - Alzheimer's disease is diagnosed ever more frequently and this requires more precise clinical and laboratory diagnostic methods. The authors discuss the diagnostic criteria and principles of diagnosis in this disease. Neuropathological lesions are described which are required for reliable diagnosis of the disease. Much attention is given to neuroradiological methods, including nuclear magnetic resonance and positron emission tomography. PMID- 2219921 TI - [Duodenal pressure ulcer as a cause of anemia]. AB - A case is presented of anaemia which was caused by decubitus ulcer and fistula of the duodenum developed as a result of pressure exerted by aortofemoral vascular prosthesis. PMID- 2219922 TI - [Pleomorphic lipoma]. PMID- 2219923 TI - [The frontonasal dysplasia syndrome (DeMyer's syndrome) in a newborn aged two weeks]. AB - A description is presented of a rarely observed frontonasal dysplasia (DeMyer's syndrome) whose diagnosis confirmed by X-ray and ophthalmological examinations was based on demonstration of a wide midline cleft of the facial skeleton, hypertelorism of eyes, and coexisting severe and infrequently occurring in this syndrome deformity of lower extremities. The authors think that the cause of DeMyer's syndrome in this case should be sought in the action of many various harmful factors. PMID- 2219924 TI - [Level of amino acids in blood plasma as a test for exocrine pancreatic function]. AB - A well known in physiology fact is that stimulation with enterohormones (secretin, cholecystokinin) causes a steep increase in the synthesis of pancreatic enzymes, and this might affect the plasma level of amino acids. In view of this, this level was studied in healthy subjects and patients with chronic pancreatitis. Hormonal stimulation was observed to cause in healthy subjects a significant rapid fall of the levels of all amino acids, which was greatest in the 20th minute. A less evident fall of the amino acid level was observed in chronic pancreatitis. A high correlation was noted (r = 0.9) between the value of amino acid fall in plasma and the degree of failure of the exocrine pancreatic function measured with the NBT-PABA test. All results are an encouraging indication that plasma amino acid level fall may be used for the assessment of the pancreatic exocrine potential. In the analysis of individual amino acids the most significant fall was noted of methionine, serine, valine, isoleucine, glutamine and tyrosine. PMID- 2219926 TI - [Two cases of sclerosing cholangitis in a group of 127 patients with nonspecific enteritis]. PMID- 2219925 TI - [Functional hyperbilirubinemias. Clinical, biochemical and morphological findings]. AB - Eighty-three cases of functional hyperbilirubinaemia (non-conjugated, non haemolytic hyperbilirubinaemia) were subjected to clinical, biochemical, and morphological analysis. Men accounted for almost 80% of patients, the mean age at time of first manifestations of the disease was 26 years. Persistent jaundice was present only in 31% of cases. The mean non-conjugated bilirubin level was 2.8 mg%. The so-called hunger test is very spectacular, but its diagnostic value must be evaluated cautiously. It was found that alkaline phosphate activity and BSP retention test were not in all cases normal. Other biochemical tests gave normal results. Percutaneous liver biopsy was carried out in 71 patients without finding any changes in 42%, while in others slight, mainly degenerative changes in 42%, while in others slight, mainly degenerative changes were demonstrated. In most cases the diagnosis of non-conjugated, non-haemolytic hyperbilirubinaemia can be made on the basis of clinical and biochemical evaluation. Only few doubtful cases should be qualified for liver biopsy. PMID- 2219927 TI - [Two types of electromechanical coupling in myocardial myocytes]. AB - Sarcoplasmic reticulum (SR) of isolated myocytes of guineapigs deprived of Ca2+ by means of short exposure of the cell to caffeine does not re-uptake Ca in the quiescent cell. In rat Ca2+ SR content is promptly recovered under the same experimental conditions. The results of this study confirm the two types of excitation-contraction coupling in isolated myocyes of gineapig and rat hearts: without Ca uptake and with Ca uptake between excitations, respectively. PMID- 2219928 TI - [Caffeine blood concentration as an indicator of liver damage in patients with cirrhosis--correlation with Child's classification]. AB - In 25 patients with cirrhosis fasting caffeine blood concentration was determined and the results were compared with Child's liver function sufficiency score. The caffeine blood concentrations in patients were higher than those in healthy controls (p less than 0.0001). Differences in comparison with controls were the more evident the greater was the degree of liver damage. Caffeine concentrations correlated well with the score indicating the sufficiency of the organ according to Child (R = 0.61; p = 0.002). PMID- 2219929 TI - [Studies of vitamin A metabolism in malignant neoplasms]. AB - Retinol concentration in the serum was determined in 600 healthy subjects and 250 cancer patients, including 116 patients with large bowel cancer, 90 with adenomas of the large bowel and 23 with cancer developing inn large bowel adenoma. Moreover, vitamin A concentration was determined in the liver obtained during autopsy from 23 patients dying from cancer and 34 dying from other chronic non cancer diseases. A significantly lower serum retinol concentration was confirmed in patients with cancer, but it depended on the degree of disease progression, since a significantly lower retinol concentration in relation to healthy subjects was found only in advanced neoplasms. In patients with adenoma or cancer in adenoma the serum retinol level was normal. Moreover, retinol concentration lower before the operation returned to normal after the operation. On the other hand, in patients dying from cancer previous operation was without effect on the low serum retinol level. Tissue examinations showed significantly decreased vitamin A concentration in the liver of patients dying from cancer. The results of this study indicate that reduced serum retinol concentration is rather a consequence of the malignant process and is due to impaired retinol release from the liver blood. Long-lasting malignant process may also lead to an actual vitamin A deficiency in the organism. PMID- 2219930 TI - [Primary biliary cirrhosis--analysis of clinical material]. AB - The analysis is presented of 67 patients with primary biliary cirrhosis treated in the years 1971-1988. The group consisted of 60 women (89.5%) and seven men (10.5%). Presenting symptoms were mostly itching (66%) and jaundice (12%). The time between the onset of the first symptoms and the diagnosis was three years, on the average. Autoantibodies to mitochondria were present in 86% of patients. In 27% of cases markers of HB virus infection were found. Cholelithiasis was present in 19 patients (28%). Primary biliary cirrhosis was diagnosed with delay. Third degree of histological changes was observed in 38.8% of cases and in 18% of patients it was already fourth degree. Eighteen patients (27%) died after six years, on the average, from the onset of symptoms. The direct causes of death were, most frequently, liver failure and haemorrhage from oesophageal varices. PMID- 2219931 TI - [Regulation of triiodothyronine levels in fatty tissue in obese patients]. AB - Specific activity of T4-5'-deiodinase, the enzyme which catalyze peripheral production of triiodothyronine (T3) from thyroxine (T4) has been evaluated in the subcutaneous adipose tissue of obese patients. In lean healthy women (BMI less than 21) mean activity of T4-5'-D was found to be 122 +/- 29.4 fmol T3/mg of protein/min and was higher then respective activity of the enzyme in adipocytes of patients with mild obesity (22 less than BMI less than 30) where the mean was 92.14 +/- 18.05 fmol T3/mg/min. The activity of T4-5'-D was significantly decreased in patients with severe obesity (BMI less than 30) when compared with respective activity of the enzyme found in controls (47.36 +/- 18.4 fmol T3/mg/min vs 122.4 +/- 29.4 fmol T3/mg/min; p less than 0.01). As T4-5'-D in human adipose tissue has been previously characterized as type II of the enzyme, diminished activity found in obese subjects means that thyroid metabolic activity of adipocyte is decreased. Such a state would lead to antilipolytic action of catecholamines in obesity. PMID- 2219932 TI - [Obesity as a risk factor for ischemic heart disease]. AB - The occurrence of risk factors for ischaemic heart disease in obesity is discussed. The presented view is based on the review of literature and own preliminary experiences. The importance of the distribution of the fatty tissue was shown for the medical practice. Android-type obesity increases the probability of the occurrence of metabolic disturbances leading to ischaemic heart disease. PMID- 2219933 TI - [The effect of omega 3 fatty acids on serum lipoproteins]. PMID- 2219934 TI - [Oncological supervision of patients after colonoscopic polypectomy]. AB - The high frequency of development of new adenomas in patients after colonoscopic polypectomy (30-50%) suggests the need for periodic control examinations of the whole large bowel. The diagnostic value of rectoscopy and routine diagnostic enema is limited and these methods are not suitable for periodic control of the bowel. An important method is fiberoptic sigmoidoscopy (FSS), but it is also insufficient because neoplasms are present frequently in proximal parts of the colon. The best method for evaluation of the whole colon is coloscopy, moreover, this method makes possible removal of the found polyps. In particular cases an alternative of coloscopy may be a combination of FSS and double contrast radiological examination of the colon. The frequency of control examinations of the large bowel depends primarily on the number of removed polyps. The patients after removal of a single polyp should undergo control examinations at intervals of 4-5 years. In cases with multiple adenomas removed during the first procedure or with one large adenoma (over 2 cm in diameter) should have control examinations repeated every 2-3 years. PMID- 2219935 TI - [Physical exertion and obesity]. PMID- 2219936 TI - [Assessment of the practical skills of physicians by means of estimation scales]. AB - The method is presented of objective assessment of practical skill in clinical medicine by means of so-called estimation scales. The scales are shown used for the assessment of know-how in management of vomiting and diarrhoea and examinations testing validity and reliability of this assessment are described. PMID- 2219937 TI - [Role of coloscopy in diagnosis and treatment of large bowel diseases]. AB - Coloscopy is the most accurate method of evaluation of the whole large bowel. The main indications for this examination are doubtful radiological changes in the colon and unexplained intestinal symptoms, bleeding in the first place. Coloscopy plays also an important role in the differential diagnosis of colitis and in the oncological follow-up of patients after polypectomy or with long-standing ulcerative colitis. The therapeutic use of coloscopy includes removal of polyps and foreign bodies, control of bleeding, and laser photocoagulation of neoplasmatic lesions. Since 1973 in the Department of Gastroenterology of the Postgraduate Medical Center 2360 diagnostic coloscopies were carried out in 1838 patients. The most frequent diagnoses were polyps (34%) and large bowel cancer (12%). Various forms of colitis were diagnosed in 7% of patients, and all other diseases jointly in 11% of cases. In 36% of patients the large bowel showed no changes, in spite of undoubtful indications for coloscopy. Many of these patients were spared explorative laparotomy. By means of diathermic loop 808 colorectal polyps were removed in 421 patients. Rare complications of this procedure were bleedings (1.5%) and peritoneal irritation symptoms without perforation (0.25%). Adeneomas prevailed among polyps. Seventeen patients with invasive cancer in adenoma were treated successfully only endoscopically. PMID- 2219938 TI - [Therapy and prognosis of children with prenatally diagnosed urinary tract abnormalities]. AB - Urinary tract malformations are recognized already prenatally to an increasing extent, but the indications for, and the time of surgical intervention are still a matter of debate. The present study is an analysis of the data collected over an 80-month period of 76 patients whose urinary tract malformation was suspected prenatally and confirmed after birth. Patients with lethal malformations whose disease led to abortion or intrauterine death were excluded. Ureteropelvic junction obstruction was present in 47% of the patients and obstructive uropathy accounted for 67% of all malformations. In contrast, vesicoureteric reflux was found only in eight patients. Thirty seven infants (49%) required surgical intervention and 61% of all operations were performed during the first month of life. 57% of these early interventions were temporary diversions. The indication for surgical treatment was based on sonographic and radiological assessment of the malformation and on the results of functional assessment. In many instances surgery was delayed until indicated on the basis of the findings of the follow-up studies. All reconstruction operations were successful. Prenatal diagnosis benefitted most children, especially those with the most severe malformations. No patient died as a result of the renal condition and the prognosis is grave in only one child, who is likely to go into terminal renal failure in childhood. PMID- 2219940 TI - [Automated exchange transfusion in premature and newborn infants with hyperbilirubinemia using a peripheral arteriovenous vascular access device]. AB - The technique of exchange transfusion using a plastic catheter in the umbilical vein developed by Diamond and modified by Allen was instrumental in decreasing the mortality and morbidity in newborn infants with jaundice. Allen et al. demonstrated that the development of kernicterus in infants with erythroblastosis with indirect hyperbilirubinemia could be prevented by this method. Since that time numerous modifications of this "single site, push pull technique" have been described to further reduce the risk of morbidity and mortality. On the basis of the successful use of percutaneous radial artery catheters for arterial blood gas monitoring, we developed a technique for exchange transfusion using a peripheral arterial catheter inserted in the radial artery for blood withdrawal and a peripheral venous catheter for replacement of heparinized compatible donor blood. For simultaneous withdrawal and replacement we used two volumetric infusion pumps, one aspirating patients' arterial blood, the other replacing equal volumes of donor blood at exactly the same time. We evaluated our new procedure in 19 newborn infants (group 1) with hyperbilirubinemia who required exchange transfusion. Retrospectively we analysed the data in 18 newborn infants (group 2) treated over a previous period by means of the conventional "one site, push pull" technique using the umbilical vein, and compared the data. Mean birth weights, gestational ages and Apgar scores were similar in both groups, as were volumes of blood used for exchange transfusions. The results were superior in group 1 infants, as reflected by the significantly greater percentage decreases in serum bilirubin concentration and fewer complications. No baby died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2219939 TI - [Harmful effects in early pregnancy--results of a teratological counseling center]. AB - In the years 1986, 1987, and 1988 altogether 132 consultations were conducted during pregnancy at the Landesfrauenklinik Linz. These pregnant women had all been exposed to potentially harmful influences (drugs, maternal diseases and as infections or cancer, X-rays or pregnancy despite IUD). In most of the cases we recommended carrying the pregnancy to full term; only a few were interrupted, sometimes against on recommendation to proceed with the pregnancy. The rate of abortion and the frequency of ectopic pregnancies were within normal limits. Due to personal investigations after birth we registered postnatal findings in nearly all cases. No serious malformations were recorded. Detailed teratological knowledge is necessary for correct advice at consultation after exposure to harmful influences during early pregnancy. In most cases it is possible to avoid interruption without risking an increased rate of malformations. PMID- 2219941 TI - [Percutaneous cannulation of the radial artery in severely ill premature and newborn infants]. AB - Cannulation of the radial artery is an easy and safe alternative to the usual procedure of catheterization of the umbilical artery to secure blood for gas sampling and for monitoring blood pressure in critically ill neonates. The use of a fiberoptic light source further improves the success of percutaneous radial artery cannulation. We performed this procedure in 264 critically ill babies and it was successful in 211 (80%). The average weight was 2.160 g (740-4,300), gestational age was 33 weeks (26-45). The radial artery catheter had an average useful life of 5 days (1-22). In 53 newborn infants the catheter had to be removed prematurely because obtaining blood samples was no longer possible. In 15 babies the catheter had to be removed on account of arterial spasms. One patient developed skin necrosis of a small area on the tip of the thumb due to a thrombo embolic complication. No case of bacterial infection due to cannulation was observed. No neurological disturbance in hand or finger function was found on follow up after one year. In conclusion, this method is safe, easy to handle, has less complications and several advantages over previous methods. PMID- 2219942 TI - [20-year-old HIV-1-positive hemophiliac patient with conspicuous plantar warts- effects of zidovudine (Retrovir) treatment]. PMID- 2219944 TI - [Hyperlipidemia and coronary heart disease]. AB - The coronary heart disease (CHD) is of great importance, because it is the leading cause of death in the western world. There is general agreement in the scientific and medical community that high levels of cholesterol and low density lipoproteins (LDL) play a dominant role in atherosclerosis, whereas high lipid lowering agents are associated with a reduced risk for CHD. PMID- 2219943 TI - [Current findings on nocturnal catecholamine excretion in coronary patients]. AB - In 10 patients after myocardial infarction (mean age 53 +/- 8 years) with a normal ejection fraction (EF) and in 10 healthy people (mean age 52 +/- 8 years) the night urinary excretion of noradrenaline and adrenaline was investigated. Additionally to that the vanillic acid vanilmandelic acid and serotonin were determined. Our results show that patients after myocardial infarction with normal EF have significant higher noradrenaline values at night than healthy people (1.95 +/- 1.26 micrograms/h vs. 0.96 +/- 0.37 microgram/h [p less than 0.01]). The night urinary excretion of adrenaline was also increased in patients after MI, but there were no significant differences between the 2 groups (0.51 +/ 0.28 microgram/h vs. 0.27 +/- 0.14 microgram/h [p less than 0.1]). Serotonin was higher in patients with coronary heart disease (CHD), but there was also no significant difference (0.15 +/- 0.14 mg/h vs. 0.08 +/- 0.05 mg/h). Cholesterol values were significantly higher in patients with CHD (245 +/- 56 mg%) than in the group of healthy people (177 +/- 45 mg% [p less than 0.01]). Our own results are of great interest because we found out (to our knowledge for the first time) that patients with CHD show significant higher levels of urinary noradrenaline excretion during the night than healthy volunteers. The raised noradrenaline values may present a particular risk factor for coronary heart disease. PMID- 2219946 TI - [Vascular surgery in Austria--report on the 21st annual meeting in Eisenstadt]. AB - The Austrian Society for Vascular Surgery exists since 21 years. At the beginning of October 1989 she held her Annual Meeting in Eisenstadt, Burgenland, Austria. The topics of this well-attended meeting were: Surgery of the vertebral artery, the external carotid artery, and the deep femoral artery. The last scientific experiences in diagnosis and therapy, especially in surgical therapy, were reported. In the session Angiochirurgicum interesting cases, new diagnostic procedures, new vascular surgical techniques, new instruments, and new bypass materials were introduced. Both the selected topics and the great number of attendees showed that the Austrian Society for Vascular Surgery is an up to date and active scientific association which follows this special field of surgery into its most subtle ramifications, and has proved a success compared to international standards. Active international exchange of views leads to an improvement and standardization of surgical results and is thus for the benefit of the patients. PMID- 2219945 TI - [Ophthalmological significance of stenosing carotid processes]. AB - In a retrospective study we looked at the incidence of carotid artery stenosis in 191 ophthalmological patients, which underwent duplex sonography. In all these patients the oculist had considered carotid artery stenosis to be a possible reason for the present eye disease or visual disturbance. The incidence of stenosis found in these patients was compared to a group of 186 persons of the same mean age, which underwent routine-sonography without suffering from any symptoms related to carotid artery disease. Patients with amaurosis fugax, with occluded retinal veins and patients with glaucoma associated changes of the retina (in spite of normal eye pressure) suffered more often from carotis stenosis than asymptomatic persons (statistically significant), patients with occluded retinal arteries showed also more often carotid artery stenosis than the asymptomatic collective but without statistical significance. We conclude, that patients presenting with the mentioned symptoms should undergo carotid artery sonography. Furthermore these results could be of importance in evaluation the indication for carotid thrombendarterectomy (stadium II of cerebrovascular insufficiency). PMID- 2219947 TI - [The relevance of diet for civilization diseases, especially atherosclerosis]. AB - Atherosclerosis is a consequence of modern civilization and nutrition. It became a problem due to higher life-expectancy and changed nutritional habits. This is discussed in relation to myocardial infarction, gout and inborn errors of metabolism and modern nutrition. PMID- 2219948 TI - [Atherosclerosis and possibilities of dietary prevention or therapy]. AB - Hypercholesterolemia, hypertension, smoking and diabetes mellitus are the main risk-factors for the development of early atherosclerosis. The association of hypercholesterolemia and atherosclerosis is well established: there is a strong correlation of the duration and severity of atherosclerosis to the extend of plaque-formation. Dietetic measures in large populations show reduction in cardiovascular events, drastic lipid-lowering therapy (i.e. drugs, plasma exchange, ileum-bypass operation) may induce regression of plaque-formation. PMID- 2219949 TI - [Atherosclerosis: sugar, weight reduction, trend towards thinness]. AB - Sugar by itself is not a factor in the etiology of atherosclerosis. It is only in fostering overweight. The reasons for the public discussion of sugar in nutrition are tentatively analyzed. PMID- 2219950 TI - [Fats in the diet]. AB - The importance of nutritional fats as a source of energy declined in the past in industrialized countries due to a decrease of physical activity. On the other hand the association between the intake of particular fats and the development of cardiovascular diseases is generally accepted. Thus, some scientific societies (American Heart Association, NIH Consensus Development Conference) recommend a maximal intake of 30% of total energy by fats. In regards to the quality of fats and their effect on blood levels of lipoproteins, it is accepted that large amounts of polyunsaturated fatty acids lower increased blood levels of low density lipoproteins; however, they lower in a small extent also the antiatherogenic high-density lipoprotein (HDL) particles. Monounsaturated fatty acids also tend to lower increased LDL, without any lowering effect on HDL, W-3 fatty acids (mainly from fish oil) lower increased triglyceride levels and therefore are used a therapeutic dietary regimen. However, their long-term effects are not quite well known. PMID- 2219951 TI - Effect of pyridoxine on the disposition and lymphopenic effects of 2-acetyl-4(5) tetrahydroxybutyl imidazole in the rat. AB - 1. 2-Acetyl-4(5)-tetrahydroxybutyl imidazole (THI) administered orally to rats markedly decreased the peripheral blood lymphocyte count within 16-24 h. The lymphopenic effect of THI was prevented by co-administration of pyridoxine. 2. 14C-THI, administered orally, was absorbed in a dose-dependent manner and excreted unmetabolized. These processes were not affected by co-administration of pyridoxine. 3. In contrast, the rate of excretion of 14C-THI administered i.v. was increased by both dietary and parenterally-administered pyridoxine, and pyridoxine decreased the amount of radiolabel associated with lymphoid tissues. 4. The results show that the lymphopenic effect of THI is not sustained once it is excreted, and indicate that pyridoxine and THI may compete for the same binding site in lymphoid tissues. PMID- 2219952 TI - Metabolic studies on pentachlorophenol (PCP) in rats. AB - 1. The metabolism of pentachlorophenol in rats was studied. 2. Metabolites isolated from rat urine and identified were: 2,3,4,5-tetrachlorophenol, 2,3,4,6 tetrachlorophenol, 2,3,5,6-tetrachlorophenol, tetrachlorocatechol, tetrachlororesorcinol, trichlorohydroquinone, tetrachlorohydroquinone, and traces of trichloro-1,4-benzoquinone, and tetrachloro-1,4-benzoquinone. PMID- 2219953 TI - Fungal metabolism of 4-substituted amphetamines. AB - 1. rac.-4-Ethoxyamphetamine was incubated with 14 different yeast and fungal microorganisms. 4-Hydroxyamphetamine was the major metabolite; traces of N-acetyl 4-ethoxyamphetamine were also detected. 2. The major fungal (Cunninghamella) metabolite of 4-propoxyamphetamine and 4-benzyloxyamphetamine was 4 hydroxyamphetamine. The major metabolites of 4-methoxyamphetamine were N-acetyl-4 methoxyamphetamine and 4-hydroxyamphetamine. 3. Acetoin derivatives were formed when alkoxyamphetamine substrates were incubated in the presence of various fungi and yeasts. 4. The findings indicate that Cunninghamella echinulata may be a useful microbial model for drug disposition and interaction studies. PMID- 2219954 TI - Biliary excretion and intestinal metabolism in the intermediary metabolism of pentachlorothioanisole. AB - 1. Biliary metabolites from rats dosed with pentachlorothioanisole (PCTA) were characterized by fast atom bombardment mass spectrometry and electron impact mass spectrometry. 2. Most of the biliary metabolites from PCTA were mercapturic acid pathway metabolites of methylsulphinyltetrachlorobenzene (51% of the dose); the remaining characterized biliary metabolites (20%) were mainly methylsulphinyltetrachlorothiophenols excreted as unknown conjugates. 3. Pathways are proposed for the intermediary metabolism of PCTA to bis (methylthio)tetrachlorobenzene (bis-MTTCB) involving glutathione conjugation, biliary excretion, intestinal metabolism, and enterohepatic circulation. PMID- 2219955 TI - Dissimilation of 2,4-dichlorophenoxyacetic acid by Azotobacter chroococcum. AB - 1. A strain of Azotobacter chroococcum which could use 2,4-dichlorophenoxyacetic acid (2,4-D) as sole carbon source was isolated. 2. The strain metabolized 2,4-D via p-chlorophenoxyacetic acid, p-chlorophenol and 4-chlorocatechol; the last metabolite was cleaved by catechol 1,2-dioxygenase. 3. The enzyme exhibited broad substrate specificity. PMID- 2219956 TI - Formation of amphetamine from its nitro analogue by anaerobic intestinal bacteria. AB - 1. Microbial reduction of 1-phenyl-2-nitropropane 1 was carried out using 40 strains of intestinal anaerobic bacteria. Among them, 12 strains (Mitsuokella multiacidus, Clostridium perfringens, C. innocuum, C. clostiriiforme, C. difficile, C. butyricum, C. sp., Eubacterium limosum, E. aerofaciens, E. multiforme, Peptostreptococcus anaerobius and P. productus) had the ability to reduce 1 to amphetamine 2 (0.1-1% yield). 2. Clostridium species were more active than another intestinal anaerobic bacteria. 3. When Clostridium perfringens was used in preparative fermentation, the yield of 2 was increased, and its absolute structure had an (S)-configuration with an optical purity of 68% in enantiomeric excess. PMID- 2219957 TI - Comparison of digoxin analysis by high-performance liquid chromatography/post column derivatization and fluorescence polarization immunoassay. AB - 1. This study compared the analysis of digoxin using a high-performance liquid chromatographic post-column derivatization (HPLC-PC) assay and the TDx fluorescence polarization immunoassay (FPIA). 2. Serum obtained from 15 digitalized patients showed higher mean digoxin levels with the FPIA method as compared to the HPLC-PC procedure such that the mean HPLC-PC/FPIA ratio was 0.91 +/- 0.14 (mean +/- SD). Demonstrated cross-reactivity of digoxin metabolites with the FPIA is probably responsible for this observation. 3. Cross-reactivity of the immunoassay towards endogenous material present in serum samples from certain patient groups was an even greater problem, with apparent 'digoxin' serum concentrations in untreated hepatic failure patients being within the therapeutic range for digoxin. 4. The HPLC-PC method did not suffer from such interference and would therefore provide more accurate values for patients where high levels of interference could contribute to false digoxin levels. PMID- 2219958 TI - Disposition of ampiroxicam, a prodrug of piroxicam, in man. AB - 1. Ampiroxicam, a prodrug of the effective anti-inflammatory agent piroxicam, was completely converted to piroxicam after oral administration to man. 2. At clinical doses there was no detectable portal or systemic exposure of man to ampiroxicam, indicating that conversion to piroxicam was complete during the absorption process. 3. The pharmacokinetics of piroxicam from ampiroxicam were essentially the same as those after piroxicam itself except that Cmax was slightly lower and tmax was slightly longer after administration of ampiroxicam. PMID- 2219959 TI - Conjugation of chemical carcinogens by primary cultures of human hepatocytes. AB - 1. The conjugation of benzo[a]pyrene (BP) and 2-acetylaminofluorene (AAF) was investigated in primary cultures of human hepatocytes. Human hepatocytes conjugated 12.5-63% of the BP and 1.7-52% of the AAF to sulphates and glucuronides over a thousand-fold concentration range. 2. BP is conjugated to glucuronides from non-detectable levels to 50%, and to sulphates from non detectable levels to 30%. The major conjugated metabolites are the highly polar metabolites. 3. AAF is conjugated to glucuronides from 1.5 to 51% and to sulphates from 0.2 to 12%. The C-hydroxylated AAF metabolites were conjugated to glucuronides more than N-hydroxy AAF and aminofluorene metabolites. PMID- 2219960 TI - Absorption, distribution and excretion of lacidipine, a dihydropyridine calcium antagonist, in rat and dog. AB - 1. The absorption, distribution and excretion of lacidipine have been studied in rat and dog after i.v. (0.05 mg/kg for rat; 0.5 mg/kg for dog) and oral dosage (2.5 mg/kg for rat; 2.0 mg/kg for dog). 2. Lacidipine was rapidly and extensively absorbed after oral dosing, in both species. Oral bioavailability was up to 26% in rat and up to 32% in dog, due to extensive first-pass metabolism. 3. After oral administration, peak levels of radioactivity were reached at 4-8 h in rat and 1-2 h in dog. Unchanged lacidipine peaked at 1-2 h in both species. Plasma levels of radioactivity were higher in female rats than in males but there was no difference in levels of unchanged drug. 4. After i.v. dosing the terminal half life of unchanged drug was 2.9 h in rat and 8.2 h in dog. The half-life of radioactivity in plasma was longer in both species. 5. After both routes of administration, radioactivity was rapidly distributed in rat tissues with the highest concentration in liver, fat and gastrointestinal tract. Only traces of radioactivity were detected in the CNS and in rat foetuses. 6. Extensive biliary elimination occurred, and most of the radioactivity (73-95%) was excreted in the faeces after i.v. or oral administration. 7. The compound was extensively metabolized, no significant amount of unchanged drug was excreted in bile or urine. PMID- 2219961 TI - In vitro metabolism of the antianxiety drug buspirone as a predictor of its metabolism in vivo. AB - 1. Metabolism of the antianxiety drug buspirone was studied by in vitro incubations with rat liver microsomes and hepatocytes. Metabolites were isolated and purified by h.p.l.c. The purified metabolites were identified by co-elution on h.p.l.c. with authentic standards and by g.l.c.-electron impact mass spectrometry of their trimethylsilyl (TMS) derivatives. 2. Five metabolites of buspirone were identified in the microsomal incubates and seven in the hepatocyte incubates. The major metabolites arose from aromatic hydroxylation at C-5, N dealkylation of the butyl chain, and hydroxylation at C-6' and C-3' on the azaspirodecanedione moiety. 3. Metabolism of buspirone by rat liver microsomes was NADPH-dependent and was completely inhibited by cytochrome P-450 inhibitors SKF-525A and metyrapone. 4. Metabolites of buspirone formed in vitro were good predictors of the primary metabolites formed in vivo. 5. Hepatocytes and phenobarbital-induced rat liver microsomes were better predictors of in vivo metabolism of buspirone than non-induced rat liver microsomes. These in vitro systems should provide excellent models for studying the metabolism of other azaspirodecanedione-containing drugs. PMID- 2219962 TI - Interspecies comparison of the metabolic pathways of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor. AB - 1. The metabolism of perindopril (non-thiol angiotensin-converting enzyme inhibitor) was studied in rat, dog and monkey after single oral and i.v. administration of 14C-perindopril, and in man after a single oral dose. 2. Six biotransformation products of perindopril from urine, faecal and plasma samples (bile only for rats) were identified. 3. The main route of biotransformation in all species is the hydrolysis of the carboxylic ethyl ester side-chain, with the formation of perindoprilate, the active metabolite. 4. A minor route of biotransformation led to the acyl glucuronides of perindopril and perindoprilate. 5. Internal dehydration of perindopril and perindoprilate into cyclic lactam structures occurs. This route of metabolism is of minor importance except in humans. PMID- 2219963 TI - Evidence for the absence of cysteine S-conjugate N-acetyltransferase activity in the metabolism of propachlor, naphthalene, and dichlobanil in calves. AB - 1. The glutathione conjugate of 2-chloro-N-isopropyl[1-14C]acetanilide (14C propachlor) was perfused through a calf kidney in situ; 23% of the dose was excreted in the perfused kidney urine as the cysteine conjugate, no mercapturic acid was detected. 2. A 5-day-old calf dosed orally with 14C-propachlor excreted 70% dose in the urine as the cysteine conjugate; no mercapturic acid was detected. Rumen microflora were established in the calf (5 weeks older) and the experiment was repeated with the same results. 3. When the same calf was dosed 1 week later with 14C-naphthalene, 99% dose was excreted in the urine, mostly as the dihydrodiol-glucuronide (34%) and the dihydrohydroxy-cysteine conjugate (47%); no mercapturate was detected. 4. A 9-day-old calf dosed orally with 2,6, dichlorobenzo[14C]nitrile (14C-dichlobanil) excreted 67% dose in the urine as cysteine conjugates (34%), and products of cysteine conjugate beta-lyase cleavage of cysteine conjugates (30%); no mercapturates were detected. 5. Cysteine S conjugate N-acetyltransferase activity in calf kidney and liver was about 10% of that in the corresponding rat tissues. PMID- 2219964 TI - Oxidative transformation of paxilline in sheep bile. AB - 1. 14C-Paxilline incubated in bile from pasture-fed sheep was efficiently transformed to a more polar dioxygenated derivative in which the indole 2,3 double-bond had opened to give an 8-membered ring. The structure is proposed on the basis of mass spectrometry and 1H- and 13C-n.m.r. spectroscopy. The new compound is 2,18-dioxo-2,18-seco-paxilline. 2. The paxilline transformation also occurred in bile which had been boiled to inactive enzymes. 3. The dissolved oxygen concentration in freshly collected sheep bile was in the range 38-163 nmol/ml. 4. Whereas paxilline causes pronounced tremor in the mouse given 4 mg/kg i.p., the dioxygenated paxilline was biologically inactive at ten times this dose. 5. The feasibility that analogous oxidative transformation of indole diterpenoid tremorgenic mycotoxins may occur, increasing polarity advantageously to xenobiotic elimination, during biliary elimination from agricultural ruminants in the field, is recognized. Concomitant loss of tremorgenicity is an additional benefit. 6. The biotransformation of paxilline in sheep bile was mimicked by ozonolysis but the ozone equivalent 4-t-butyl-iodoxybenzene was not similarly effective. PMID- 2219966 TI - Effects of blockage of urine and/or bile flow on diflunisal conjugation and disposition in rats. AB - 1. The effects of surgical blockage of either or both of the urinary and biliary excretion routes on the elimination of diflunisal (DF) and its conjugates were investigated in pentobarbitone-anaesthetized rats given DF at 10 mg/kg i.v. 2. In control animals the acyl glucuronide and phenolic glucuronide conjugates were excreted predominantly in bile, whereas the sulphate conjugate was eliminated almost exclusively in urine. 3. Bilateral ureter ligation had little effect on DF elimination, except for accumulation of the sulphate conjugate in plasma. Compensatory biliary excretion did not occur. 4. Total plasma clearance of DF decreased from 1.01 to 0.68 ml/min per kg following bile duct ligation. Plasma concentrations and urinary excretion of the glucuronides were elevated. 5. In rats with blockage of both urinary and biliary excretion routes, total plasma clearance of DF decreased to 0.59 ml/min per kg. Both the sulphate and phenolic glucuronide conjugates accumulated in plasma, whereas the acyl glucuronide peaked at 30 min and then declined in parallel with DF. The latter result indicates systemic instability of DF acyl glucuronide with hydrolytic regeneration of DF as the likely major consequence. PMID- 2219965 TI - Mechanism of formation of 6-amino-5-(N-methylformylamino)-1-methyluracil and 3,7 dimethyluric acid from theobromine in the rat in vitro: involvement of cytochrome P-450 and a cellular thiol. AB - 1. The involvement of glutathione (GSH) and cytochrome P-450 in the conversion of theobromine to 6-amino-5-(N-methylformylamino)-1-methyluracil (3,7-DAU) and 3,7 dimethyluric acid (3,7-DMU) has been investigated in rat liver microsomal incubations. 2. The ratio of formation of 3,7-DAU to 3,7-DMU increased with increasing GSH concentration, reaching a maximum (approximately 12:1) at 2 mM. For any given added GSH concentration the formation of 3,7-DAU plus 3,7-DMU remained constant. 3. 3,7-DAU and 3,7-DMU formation were increased approx. 12- and 1.6-fold in liver microsomes from rats treated with 3-methylcholanthrene and phenobarbitone, respectively. Cimetidine, metyrapone and SKF-525A each inhibited the conversion of theobromine to 3,7-DAU and 3,7-DMU. 4. Apparent Km and Vmax values for the combined formation of 3,7-DAU and 3,7-DMU were the same in the absence and presence of GSH, 2 mM. 5. L-Cysteine and N-acetyl-L-cysteine were as effective as GSH in causing a shift from 3,7-DMU to 3,7-DAU formation, but the non-thiol reducing agents ascorbic acid and alpha-tocopherol were ineffective. 6. Data are consistent with the hypothesis that 3,7-DAU and 3,7-DMU are derived from a common oxidized intermediate of theobromine, the formation of which is rate limiting. The putative intermediate normally serves as a precursor to 3,7-DMU but in the presence of GSH, or some other cellular thiol, it may be reduced to give 3,7-DAU. PMID- 2219967 TI - Comparative metabolism of high doses of aspirin in man and rat. AB - 1. Metabolism of aspirin was studied in 10 human volunteers who took a therapeutic dose (600 mg) by mouth and in nine patients who took aspirin in overdose. 2. Salicyluric acid was the major urinary metabolite in volunteers (63.1 +/- 8.4% of dose in 0-8 h). In overdose patients, salicyluric acid in urine was decreased (30.0 +/- 8.2%, 0-24 h, P less than 0.001) and there was increased elimination of salicyclic acid (34.1%, P less than 0.005), salicyl acyl glucuronide (14.4%, P less than 0.05) and gentisuric acid (5.3%). 3. Metabolism of orally administered 14C-aspirin in rats over a 10-fold dose range (10-100 mg/kg) resulted in excretion of 81-91% dose in urine in the first 24 h. Salicyclic acid was the major urinary metabolite (43-51% dose). Excretion of salicyluric acid decreased with increasing dose, whereas gentisic acid and salicyl phenolic and acyl glucuronides increased. 4. The profile of aspirin metabolites was qualitatively similar in man and rat but there were quantitative differences. Limited capacity to form salicyluric acid was observed in both species. Dependence on this pathway in rat was low and was compensated by increased utilization of other routes; dependence on salicyluric acid formation in man was high and in overdose, compensation by other routes was incomplete. PMID- 2219969 TI - Treatment of bone tumors around the shoulder joint by the Tikhoff-Linberg procedure. AB - The Tikhoff-Linberg procedure is a limb-sparing surgical option to be considered for bony and soft tissue tumors in and around the proximal humerus and shoulder girdle. The authors reported 6 cases of the Tikhoff-Linberg procedure for tumors around the shoulder joint at the Department of Orthopedic Surgery of Severance Hospital from March 1988 to May 1989. The results of the study are as follows: The 6 cases were composed of: osteogenic sarcoma 2 cases, chondrosarcoma 2 cases, chondroblastoma 1 case, and giant cell tumor 1 case. The tumors were completely removed by the Tikhoff-Linberg procedure without amputation or disarticulation of the upper extremity. The distal clavicle, upper humerus and part of all of the scapula were resected. The Tikhoff-Linberg procedure was performed for patients whose tumors did not involve the neurovascular bundle in the axilla. The function of the hand and forearm after the Tikhoff-Linberg procedure was nearly normal in all cases. The Tikhoff-Linberg procedure would be recommended as a limb-sparing operation for tumors around the shoulder joint that require wide resection without disarticulation or forequarter amputation of the upper extremities. PMID- 2219968 TI - The effect of experimental trypsin on the regeneration of hyaline articular cartilage. AB - There is evidence from other studies that some degree of cartilage healing may take place after the initiation of an inflammatory response. It is postulated that the induction of the platelet-cartilage interaction may eventuate in cartilage repair. The treatment of fresh articular cartilage with proteolytic enzymes rendered the tissue active as a platelet aggregant. During platelet aggregation a host of active substances are released which are known to play a role in the inflammatory response (Thompson 1975). This study was undertaken to evaluate the effects of trypsin on the surface injury of rabbit hyaline cartilage. The results were as follows: 1) Hyaline cell regeneration was observed only in the group treated with trypsin and blood; 2) Hyaline cartilage regeneration did not occur in the group treated with a single injection of trypsin or blood; 3) There was no significant damage to the healthy articular cartilage by the single injection of trypsin or blood, or both; and 4) Platelets do not adhere to cartilage and superficial damaged cartilage does not induce platelet aggregation. PMID- 2219971 TI - Congenital dislocation of the hip--a long-term follow-up in Korea. AB - The results of fifty-eight congenitally dislocated hips in fifty-four children, who were between two months and eleven years old when treatment was begun, have been reviewed. Thirteen hips were treated by closed reduction, seventeen hips by open reduction, seventeen hips by Salter's innominate osteotomy, five hips by Klisic operation, and six hips by other operations. At an average 5.1 year follow up (range, three to twelve years), a 91% satisfactory result was obtained when treatment was started under two years of age. With preoperative traction, in the cases when the femoral head was pulled down below to the zero station, the clinical result was satisfactory in 83%. We think that the treatment of congenital dislocation of the hip should be started before two years of age and that the femoral head should be pulled down below to the zero station to prevent avascular necrosis, and to obtain a satisfactory result. PMID- 2219970 TI - Non-Hodgkin's lymphoma: a histopathologic and immunohistochemical study of 79 cases. AB - Recently immunophenotyping has become a valuable tool in the diagnostic workup of malignant lymphoma. We classified 79 consecutive cases of non-Hodgkin's lymphoma experienced at our hospital during the last two years according to the Working Formulation and immunologically using MT1, UCHL1 and MB2 monoclonal antibodies. The results of this study are as follows: 1) four cases (5.1%) were low grade, 54 cases (68.4%) were intermediate grade, and 21 cases (23.3%) were high grade. The most common subtype was 'diffuse, mixed' type, 2) fifty cases (63.3%) showed T cell phenotype and 14 cases (17.7%) showed B-cell phenotype. Immunophenotyping was impossible in 15 cases due to either double staining or negative staining. 3) the incidence of extranodal presentation was high (65.8%) and the most common extranodal site was the upper aerodigestive tract (29.1%) followed by the gastrointestinal tract (16.4%), and 4) MT1, UCHL1 and MB2 monoclonal antibodies are valuable markers of T- and B-cells in paraffin embedded tissue, enabling retrospective study. However, because these antibodies are not lineage specific, the results of immunostaining should be interpreted with caution. PMID- 2219972 TI - Comparison of adjuvant radiotherapy and chemoradiotherapy following surgery in stage IE and IIE primary gastrointestinal tract non-Hodgkin's lymphoma. AB - Forty patients (median age 49.6 years) were treated for primary gastrointestinal lymphoma between 1979 and 1989. There were twenty-three cases of gastric lymphoma and seventeen cases of intestinal lymphoma. Following surgery, seventeen patients received postoperative chemoradiotherapy (ACOP) by the sandwich technique, seven patients received postoperative radiotherapy, and sixteen patients did not receive any other form of adjuvant treatment. Nineteen patients were stage IE and twenty-one were stage IIE. Stage IE disease was more prevalent in the gastric lymphoma group than the intestinal lymphoma group (p less than 0.01). At a median follow-up of 17 months (1-102 + months), 17 of 19 stage IE patients and 15 of 21 stage IIE patients remained alive. The survival rate was 90% in the postoperative chemoradiotherapy group and 83.3% in the postoperative radiotherapy group at five years, and 42.7% in the surgery alone group at four years, which showed statistical significance (p less than 0.01, p less than 0.05, each). Statistically improved survival rates were achieved with a postoperative chemoradiotherapy modality in intestinal lymphoma (p less than 0.01), stage IIE (p less than 0.01), intermediate grade by NCI criteria (p less than 0.01), poorly differentiated lymphocytic lymphoma (p less than 0.05), and diffuse histiocytic lymphoma (p less than 0.01) according to Rappaport classification, compared to those of the surgically treated only group. Three local relapses occurred in the operation alone group, and one in the adjuvant radiotherapy group which occurred simultaneously with distant lymph node recurrence. The pathologic stage of all of these relapsed patients was stage IIE-2. These results suggest that adjuvant chemoradiotherapy in completely resected localized gastrointestinal non-Hodgkin's lymphoma can decrease local and systemic relapse resulting in long-term disease free survival and overall survival compared to operation alone. PMID- 2219973 TI - Effect of tolazoline on persistent hypoxemia in severe hyaline membrane disease. AB - Ten critically-ill preterm infants with severe hyaline membrane disease received tolazoline because of persistent hypoxemia refractory to the administration of 100% oxygen and mechanical ventilation. Seven infants (70%) responded immediately with an increase in PaO2 greater than or equal to 20 mmHg in the umbilical arterial gas within 60 minutes after bolus infusion (1 to 2 mg/kg) of tolazoline. Twenty-four hours later after the tolazoline infusion, the FiO2 had been decreased from 1.0 to a mean of 0.82 +/- 0.16, and the MAP from 16.5 +/- 1.8 to 15.6 +/- 4.5 cm H2O. Four of 7 infants (57%) who had an immediate response survived, whereas none survived out of 3 infants who failed to respond initially. Three infants experienced relatively severe complications possibly related to tolazoline. There appears to be a place for the use of tolazoline in a severely hypoxemic infant with hyaline membrane disease who is being ventilated, and in whom arterial oxygenation cannot be improved by a further increase in the inspired oxygen concentration or by an alteration of ventilator settings. PMID- 2219974 TI - Benign proliferative disorders of the breast. AB - Fibrocystic disease of the breast has been generally regarded as a disorder due to either excess hormonal stimulation or an exaggerated proliferative response by hypersensitive breast epithelium. The unique lobular lesion-adenosis- and its variants have been regarded as non-neoplastic and non-preneoplastic glandular hypertrophy and hyperplasia, and have different organoid patterns and origins. We have examined a total of 242 cases previously diagnosed as 'fibrocystic disease' at the Department of Pathology with the purpose of clarifying the variants of adenosis in detail and refining the infinitely large 'fibrocystic disease' classification as non-proliferative fibrocystic change and proliferative disorders, such as epitheliosis and atypical hyperplasia. In this study, 224 cases (92.5%) were nonproliferative disease, mostly adenosis (40.1%), and 18 cases (7.5%) were proliferative disease, which consisted of moderate to florid hyperplasia and epitheliosis. PMID- 2219975 TI - Effect of polyadenylic.polyuridylic acid on the proliferative responsiveness of mouse thymus and spleen cells. AB - The effects of polyadenylic.polyuridylic acid [poly(A).poly(U)] on in vitro proliferations of thymus and spleen cells from C57BL/6 mice were investigated. Mice were injected intravenously with 30 micrograms of poly(A).poly(U) or placebo. Two days later, thymus, spleen and peritoneal cells from these mice were prepared and cultured in pooled or non-pooled conditions. Cell proliferations were assessed by the technique of incorporation of tritiated thymidine. It has been revealed that the in vitro proliferations of thymus and spleen cells as well as the productions of interleukin-1 by peritoneal adhering cells and interleukin 2 by spleen cells were significantly enhanced in the cultures of cells from poly(A).poly(U)-treated mice. These enhancing effects were observed only in the cultures of pooled cells from mice whose genetic homogeneity is suspected. Furthermore, thymus cells from poly(A).poly(U)-treated mice acted as strong responder cells but not as stimulators in one way mixed cultures. Thus, the enhanced cellular responsiveness may be mediated by the increased production of cytokines and antigen recognitions of thymus-derived cells following activations via the adjuvant effect of poly(A).poly(U). PMID- 2219976 TI - Aberrant breast tissue of the perineum--a report on two cases. AB - In this abstract we report on two cases of aberrant breast tissue of the perineum in a 41-year-old and a 42-year-old woman with the complaint of a slowly growing vulvar mass. The masses were not fixed, they were ovoid, rubbery firm and measured 3 x 2.5 and 4 x 3 cm in size. Microscopically, they revealed normal lobular architecture with focal papillomatosis in the former. PMID- 2219977 TI - Gracilis myocutaneous flap for the coverage of an extensive scrotoperineal defect and protection of the ruptured urethra and testes. AB - The use of a gracilis myocutaneous flap to overlay an extensively traumatized scrotoperineal soft tissue defect, through which both testes and the ruptured bulbous urethra were exposed, is discussed. The transplanted gracilis myocutaneous flap, which included vascularized and innervated tissue, was well taken and covered the perineal defect, exposed testes and urethral stricture both cosmetically and functionally. PMID- 2219978 TI - Current trends in human IVF and other assisted reproductive technologies. AB - The new reproductive technologies such as IVF, GIFT, ZIFT, and micromanipulation have had a profound influence on the therapeutic and diagnostic management of infertility, and in turn have resulted in better understanding of human fertilization and embryo development. While the clinical pregnancy rates in GIFT and ZIFT procedures are comparable to the natural fecundity in the population at large, pregnancy rates in IVF have been generally lower. Further investigations should be directed to improve the implantation rates, and to develop better controlled methods of multiple follicle development. Although more studies are needed, a recent report of potential utilization of nonstimulated oocytes for donor programs as well as IVF-cryopreservation was a promising new development (Cha et al. 1989). Other exciting prospects on the horizon are the possibilities of gene transfer for the treatment of certain genetic diseases and diagnostic applications of embryonal biopsy. These new technologies have also generated serious ethical and legal issues. Any ethical or legal guidelines affecting new reproductive technologies should be developed to protect all participants only when the need for regulation is clear. Ethical guidelines and appropriate legislations with contributions from the medical and scientific community are gradually being established worldwide. PMID- 2219979 TI - Reactive dye induced occupational asthma without nonspecific bronchial hyperreactivity. AB - Current asthma is often excluded by the presence of normal bronchial hyperresponsiveness. We report two asthmatic patients with normal bronchial hyperresponsiveness and one asthmatic patient with mild bronchial hyperresponsiveness (methacholine PC20; 24 mg/ml) which was presumed to be caused by sensitization and exposure to Black GR, the most frequent sensitizer among reactive dyes. They all complained of lower respiratory symptoms after work as well as at the workstation. The bronchoprovocation test with Black GR revealed isolated immediate bronchoconstrictions in all 3 patients and all had high specific IgE antibodies to Black GR-human serum albumin conjugate. After one worker continued at work for 3 days, he experienced a marked drop of methacholine PC20, and it returned to the pre-exposure level during 1 week. The other patient whose initial methacholine challenge was negative developed bronchial hyperresponsiveness on the first day after the dye bronchoprovocation, and returned to normal bronchial hyperresponsiveness on the third day. These findings suggested that patients with occupational asthma caused by reactive dye may not always have bronchial hyperresponsiveness to methacholine, and the screening program utilizing methacholine challenges may not always identify these patients. PMID- 2219980 TI - [Senile psychoses in family clinical practice]. PMID- 2219981 TI - [Management of suicidal patients]. PMID- 2219982 TI - [Dysphagia]. PMID- 2219983 TI - [Chronic dyspepsia]. PMID- 2219984 TI - [Liver cirrhosis--current aspects of diagnosis and therapy. 1: etiology, epidemiology, prognosis, diagnosis]. PMID- 2219985 TI - [Helminthiases]. PMID- 2219986 TI - [Sense and nonsense of vitamin C and E treatment]. PMID- 2219987 TI - [Adverse effects of drugs and their legal consequences]. PMID- 2219988 TI - [Current status of preventive drug therapy of thromboembolic arterial vascular diseases]. PMID- 2219989 TI - [Maxim Zetkin--addendum to his biography on the occasion of his 25th anniversary of his death]. PMID- 2219990 TI - Ultrastructural changes of air-blood-barrier and surfactant in chronic non specific lung diseases. AB - The study of changes of ultrastructure of air-blood-barrier components in comparison with indices of surfactant surface activity was carried out on fragments of lung tissue, cut from 36 patients with bronchiectasis, chronic abscess and fibrosis of post-pneumonic nature. Our data indicate, that in patients with chronic non-specific lung diseases the areas, more distant from the focus of affection, have changes, involving all the components of air-blood barrier. Dystrophic and destructive processes, taking place in some pneumocytes of the 2nd type, result in suppression of the surface active characteristics of surfactant. On the other hand, processes of compensatory nature, directed to making up a deficiency of surfactant, take place. PMID- 2219991 TI - [The lymphocyte transformation test in sarcoidosis]. AB - A suppressive effect of the sarcoidosis serum on the mitogenic stimulation of lymphocytes could be confirmed statistically (p less than 1%). But there remained a lot of deviating results in distinct individual cases which could not be explained by subdividing the material in regard to different clinical points of view. The practical utility of the LTT as a diagnostic tool in sarcoidosis is therefore very limited. The partly missing suppression or even a stimulation compared to the culture with pooled AB-sera can be interpreted by the interesting phenomenon of a concentration dependent counter-current action of the sarcoidosis serum: On suboptimal PHA-dosage undiluted serum caused a significant reduction of the transformation rate of donor lymphocytes, 1:10 diluted serum was inefficient and in a 1:100 concentration it induced a stimulation (p less than 5%). PMID- 2219992 TI - [Malignant schwannoma of the lung]. AB - A case of a histologically confirmed malignant schwannoma of the lung is reported. The pathological and clinical features, the immuno-histological diagnosis and the prognosis of the tumor are reviewed. Furthermore, the successful surgical treatment of the patient is described; he survived 7 years after the operation, and now there aren't any clinical and roentgenological signs of recurrences. PMID- 2219994 TI - [Correlations of quartz dust exposure, scleroderma and lung function]. AB - There are closed relations between progressive systemic sclerosis (PSS) and exposure to quartz dust in the GDR. The recognition of PSS as an occupational disease is regulated by law. By analysis of the dust exposed working places a limit for silica concentrations were fixed. It is unlikely, that silica concentrations below 10% in the respirable dust induce a PSS. There are no significant differences in lung function of PSS-patients with and without quartz exposure. PMID- 2219993 TI - [Coincidence of silicosis and lupus erythematosis]. AB - From 1975 to 1989 37 patients with Lupus erythematodes exposed to quartz dust over many years were observed. Thirty of them suffered from silicosis. The coincidence of silicosis and Lupus erythematodes can be an expression of a common pathogenesis. PMID- 2219995 TI - [Model and experimental animal studies of the use of hand-controlled catheter-jet ventilation (CJV) by plastic replacement of the tracheobronchial tree]. AB - Pressure and volume flow measurements were performed on a simple model of the tracheobronchial tree using a catheter-jet-ventilation apparatus. This type of respiration is particularly favourable in tracheo-bronchial surgery, i.e. resections and anastomosing, due to the experience of model as well as animal experiments. Under consideration of the particularities of catheter-jet ventilation, this type of respiration provides excellent conditions for the surgeon. This is valid for the overview of the site of operation and possible manipulation within this region. This method of respiration is suggested as a reliable tool in the hands of less skilled anaesthetists, too, for its easy handling. PMID- 2219996 TI - [Fundamental research in ultrasonic surgery. IX. Splenic surgery using cavitation ultrasound--an experimental animal study of aspiration and sealing technics with ligament FIMOMED]. AB - A farther alternative for the conservation of the spleen represents the ultrasonic aspiration and sealing technique by means of the monomeric tissue adhesive Ligament Fimomed. The effectiveness of the method was proved by histomorphologic investigations in animal experiment with the porcine spleen. The method was effective in nearly all injuries across to the longitudinal axle of the organ even with a larger parenchymal defect and also in case of splenic tumor. The control of hemorrhage succeeded promptly and surely. Not any postoperative complication appeared. PMID- 2219997 TI - [Electrophoretic studies of the composition of peripheral mononuclear cells during operations with extracorporeal circulation]. AB - The increased incidence of infections after operations can be connected with changes of the immunocompetent cells. Mononuclear blood-cells were investigated by means of the cell electrophoresis during and after operations under the extracorporeal circulation, because electrophoretically different cells correlate with several immunological phenotypes. A heavy decrease of the electrophoretic quick mobility cell population was found out on the first postoperative day above all. This change allows itself the interpretation by decreasing the T-lymphocytes connected to a relative increase of monocytes, B-cells, and immature T-cells. Besides a lower quotient of the quick and low mobility T-cells refers to a lower immunoregulatory quotient CD4/CD8 after operation. Changes of the cell composition becomes evident also in dependence on the bypass length and the blood supply. PMID- 2219998 TI - [The question of the transmissibility of the results of subcutaneous tests of biomaterials from animals to humans]. AB - The histologic estimation of the subcutaneous connective-tissue reaction at implants forms an important part of the biocompatibility test. The connective tissue capsulae around titanium implants in man, guinea-pig, and Wistar-rat were analysed by a special test system because of the question concerning the transmission of results of animal experiments on the man. The subsidence process of the thickness of the connective-tissue capsule and of the cell count per measuring fields were represented in dependence on the time. The findings showed the fundamental similar course of wound healing in man, guinea-pig, and Wistar rat by the influence of an implant. PMID- 2219999 TI - Pancreatic transplantation in the rat. An experimental model. AB - Following the induction of experimental diabetes in two groups of rats using an isograft model, a comparative study was made of two types of pancreas transplants in which several procedures were employed. The vascular anastomosis in one group were to the renal artery and vein, and in the other, to the iliac vessels. The pancreatic ducts in one subgroup were ligated, in another, they were diverted to the urinary system; in a third sub-group, they were diverted to the intestine. The results obtained for the sub-group with the transplant anastomosed to the renal vessels were the best. It is suggested that this was due to two factors: the simplicity of the technique and the short operating times. In this present work the two best methods of dealing with the exocrine secretion were diversion to the ureter and ligation of the common bile duct. The worst results were in the group with duodeno-cystostomy. PMID- 2220000 TI - [An immunomonitoring program for supervising transplant patients]. AB - Lymphocytes and monocytes with differential and activation antigens were determined by means of the flow cytometry by using monoclonal antibodies in the peripheral blood of patients after organ transplantation. Examinations of the course showed that in this way the acute activity is seized by the cellular immunosystem. Acute reject crises, systemic virus infections, as well as septic states lead to characteristic changes and these verify the diagnostic assertion of this immunomonitoring programme. PMID- 2220001 TI - [Prolongation of transplantation survival time by a PUVA treatment. Experimental and clinical results]. AB - The treatment of transplants by a combination of 8-methoxypsoralen and longwave ultraviolet radiation (PUVA) leads to prolongation of the transplants in allogeneic receivers without immunosuppression. The rejection of skin grafts in the mice could be delayed significantly. The rejection of kidney and heart allografts could be prevented completely. A significant diminution of the acute rejection crises and a raising of the one-year survival rate showed a first clinical study by means of PUVA treatment in human kidney grafts. PMID- 2220002 TI - [Behavior of pO2 on rabbit small intestine serosa, measured with the Clark electrode in different models of intestinal ischemia]. AB - The pO2 on the surface of the small intestine serosa was measured on an isolated small intestine loop of the rabbit after synchronistic arterial and venous ligature of the mesenterium, after synchronistic arterial starvation and venous ligature, and after torsion of the mesenterium. The measurements of the pO2 were carried out by means of a Clark-electrode. Different periods for the decrease of the pO2 to zero Torr were shown in the different models of intestinal ischemia. Only the difference between the synchronistic arterial and venous ligature and torsion was statistically significant. PMID- 2220003 TI - [The effect of proximal selective vagotomy on experimental gastric mucosal lesions in the rat]. AB - The influence of the proximal selective vagotomy (PSV) on the origin and the extent of experimental gastric ulcer were investigated in rats. The lesions of the gastric mucosa were caused in three groups: by stress through swimming-test, by application of phenylbutazone, and by ischemia (ligature of the left gastric and the right gastroepiploic vessels). The PSV practised a protective influence on the pharmacodynamic etiology, however, not on the stress ulcer. The areas of the ischemic gastric ulcers were larger on an average of 40% after PSV than in the control animals. The difference was not statistically significant. In case the PSV caused besides hyposecretion and hypo-acidity even passive hyperemia caused in the denervated part of the stomach then these did not produce any sufficient defence against the origin of stress ulcers and ischemic lesions. PMID- 2220004 TI - [Computer-assisted analysis of the pressure behavior of the esophagogastric junction during increase in intragastric pressure]. AB - Two factors are to determine increasing lower esophageal sphincter pressure during intragastric pressure rising mainly: 1. the active intrinsic muscle tone and 2. the efficiency of the law by La Place. The purpose of the study was to estimate the part of both of them in this measurable phenomenon. We investigated 15 healthy volunteers and 5 patients post Nissen fundoplication. A simultaneous manometric examination of gaster and LES was carried out during gradual compression of abdominal wall. Analysis of dependence of LES-pressure on intragastric pressure, based on computer usage, was established. A linear equation described this dependence with the best correlation coefficient (r = 0.98) followed by potential and exponential equation. Fundoplication caused a steeper ascent without any changing of linear character of function. Considering linear equation is compatible with the law by La Place out not with a simultaneous pressure depending change of intrinsic muscle tone, these results indicate that the law by La Place has major importance in the measurable rising of high pressure zone during intragastric pressure increasing. PMID- 2220005 TI - [Electromyographic and manometric studies of the antrum and duodenal motility in rabbits under the influence of pentagastrin in a mechanical duodenal passage disorder]. AB - The influence of a mechanical disturbance of the duodenum on the motility of the antrum and duodenum was investigated by means of the electromyography and the perfusion manometry. Thereby the effect of the pentagastrin stimulating the motility of the unstriated muscles of the gastro-intestinal tract was used for testing the function reserve of the antrum- and duodenal-muscles. After one and a half month of establishing the passage obstacle there occurs a complex disturbance of the electrical activity; the unstriated muscles does not react on a stimulating excitation. PMID- 2220007 TI - [A skin button to anchor and lead out catheters or cable links from the skin]. AB - The manufacture of a skin button for use in chronic animal experiments is described, which is made of silicone rubber and intended to anchor the exit site of intravascular catheters. The button holds the catheter permanently in the skin and can also be used to anchor connections for occlusion cuffs and cables leading to implanted measuring elements. PMID- 2220006 TI - [Experimental animal studies of the stability of colon anastomoses after supplementary fibrin glue sealing]. AB - Sutures of the colon can be insufficient or leaking. This leads in some cases to a peritonitis or sepsis sometimes with lethal outcome. Therefore experiments in animals were performed to investigate the effect of additional applied biogenic glue. Especially in the beginning of the wound healing, at the 4th postoperative day, the firmness could be improved by fibrin glue. The bursting pressure of fibrin glue sealed colon sutures was 94 mmHg, whereas only 66 mmHg was observed in the control group. This additional firmness remains over the whole observation time of 3 weeks. An intensified proliferation of the connective tissue is responsible for this observation which could be substantiated by histological investigations and by measuring the thickness of the scar. If biogenic glue is used in animals it can have the consequence that the recipient reacts with the production of antibodies, since the components of the glue are proteins from different species. Investigations of the serum of animals which had been treated with fibrin glue revealed in a part of them precipitating antibodies against fibrinogen. With regard to this observation a second application of biogenic glue must be done with the necessary precaution. PMID- 2220008 TI - [Distance holder for implanted carotid catheters]. PMID- 2220009 TI - [Bipolar impulses or direct current as an adjuvant treatment of incisional hernia? Comparative experimental animal study]. AB - The electrostimulation of the cicatricial healing in the abdominal wall were tested in 119 Wistar rats by means of bipolar rectangularly pulsed current (0.87 Hz, +/- 25 mu A) and direct current (1 mu A). Doubling of the fascia of an abdominal wall hernia was carried out in three groups of rats. In the first group the operational region was stimulated by rectangularly pulsed current, strong proliferated cicatrices were formed with premature production of fibroblasts and collagenous fibres, fast maturation, and high strength. In the second group it was stimulated by direct current, a less exact longitudinal orientation of the collagenous fibres and a slower cicatricial maturation were shown. The third group applied as a control showed a cicatricial distension up to 5 mm. The electrostimulation of the proliferation of connective tissue and cicatricial healing could be pointed out between different tissues (peritoneum and fascia). PMID- 2220010 TI - [Strengthening of cryodestruction by ultrasonic energy]. AB - The ultrasonic treatment of vital tissue with therapeutically qualified ultrasonic intensity immediate before the cryosurgery leads to a significant enlargement of the plane and the depth of the cryodestruction. This knowledge should be used in the cryosurgical treatment of inoperable carcinomas with extensive tumor mass. PMID- 2220011 TI - [Are double potentials an indication of reentry? Intra-atrial catheter mapping in atrial flutter]. AB - A local doubling of atrial potentials was demonstrated in 40 out of 49 electrophysiological investigations with intraatrial catheter-mapping during atrial flutter. Such doubled potentials can be localized in small areas of the right atrium. In these circumscribed areas the distances between the doubled potentials vary. A predilection area inside the right atrium was not detected. The doubled potentials were found in different sites varying from patient to patient: 15 times in the upper, 13 times in the middle, and 12 times in the lower areas of the atrium. In each patient there was a particular reproducible place, where the doubled potentials were found. Sequential activation time mapping seems to show atrial excitation spreading from the area where the doubled potentials were found. We interpreted these findings as evidence of a reentry-circuit. However, the reentry-circuit apparently does not use preexisting anatomical obstacles, but rather a circumscribed pathological alteration in the atrium. PMID- 2220012 TI - [Effect of cibenzoline on atrial vulnerability and value of electrophysiological methods in the treatment of paroxysmal atrial fibrillation]. AB - The effects of intravenous cibenzoline (1,5 mg/kg) on atrial vulnerability and electrophysiology were assessed in 25 patients with documented paroxysmal atrial fibrillation, in whom sustained (greater than 30 s) atrial fibrillation/-flutter was induced by programmed atrial stimulation. In seven patients atrial fibrillation persisted despite the application of cibenzoline; in eight patients induction of atrial fibrillation was not prevented. In 10 patients the induction of sustained atrial fibrillation was prevented by cibenzoline. Intraatrial conduction time and shortest ventricular cycle length during atrial fibrillation were increased by cibenzoline (p less than or equal to 0.01). The effective refractory period of the right atrium was not significantly affected. Eight patients with frequent episodes of paroxysmal atrial fibrillation received oral cibenzoline (320 mg/day) for control of paroxysmal atrial fibrillation irrespective of the efficacy of intravenous cibenzoline. Prevention of stimulation-induced atrial fibrillation predicted successful treatment of paroxysmal AF. In conclusion, cibenzoline might be effective in the treatment of atrial tachyarrhythmias. Programmed atrial stimulation seems to be helpful in the prediction of the efficacy of an antiarrhythmic treatment of paroxysmal atrial fibrillation. PMID- 2220013 TI - [Reduction in left ventricular volume and improvement in hemodynamics following intravenous administration of pimobendan (UDGG 115 BS) in dilated cardiomyopathy]. AB - Acute cardiovascular effects of 5 mg (group I, n = 6) and 10 mg (group II, n = 6) i.v. pimobendan (UDCG 115 BS) were studied by right and left heart catheterizations in patients suffering from idiopathic dilated cardiomyopathy (NYHA II and III). Before and 2.5 h after application of pimobendan left ventricular volumes and left ventricular dP/dtmax were evaluated by left heart catheterization. Right atrial pressure (RAP), pulmonary capillary wedge pressure (PCP), cardiac output (CO), heart rate, and systemic blood pressure were assessed before and 2.5, 4, and 6 h after administration of pimobendan. PCP was reduced from 12.2 +/- 7.5 to 8.3 +/- 7.1 mm Hg (p less than 0.05) by 5 mg of pimobendan, and from 18.3 +/- 6.2 to 6.2 +/- 3.4 mm Hg (p less than 0.005) by 10 mg of pimobendan. Reduction of RAP was significant only in group II (from 6.2 +/- 3.2 to 1.2 +/- 0.9 mm Hg; p less than 0.05). In contrast to other hemodynamic parameters, the significant increase of CO exhibited no dose-dependency. Only 10 mg of pimobendan induced a temporary reduction of mean arterial blood pressure. An increase in heart rate occurred only in group I and was merely transient. Left ventricular end diastolic and end systolic volume indices were clearly reduced by 5 mg as well as by 10 mg of pimobendan. A significant rise of left ventricular ejection fraction occurred only in group II. However, left ventricular dP/dtmax was increased significantly in both groups. No adverse effects were noted during acute administration of pimobendan. Therefore, intravenous pimobendan may be a useful drug in the treatment of acute cardiac failure. PMID- 2220014 TI - [Three-dimensional analysis of the regional contractility of the normal and the cardiomyopathic left ventricle using cine-magnetic resonance imaging]. AB - The left ventricular regional contractile pattern, global function and mass of normal subjects and patients with idiopathic dilated cardiomyopathy was compared using cine magnetic resonance imaging (MRI) in a short-axis imaging plane. Left ventricular ejection fraction and mass were 64.3 +/- 2.5% and 115 +/- 10 g in normal hearts and 23.5 +/- 3.1% and 194 +/- 20 g in dilated cardiomyopathic hearts (p less than 0.001 and p less than 0.002). Left ventricular end-diastolic wall thickness was homogeneous in normal hearts except for the posterior wall at the basal level, which was significantly thinner compared to the anterolateral wall and the septum (p less than 0.02). End-diastolic wall thickness in the cardiomyopathic group was significantly more heterogeneous and was thinner at the apical compared to the basal level (p less than 0.02) as well as in the segment of the posterior compared to the anterolateral and septal wall (p less than 0.005 and p less than 0.03). In normal hearts, left ventricular end-systolic wall thickness was progressively greater from base to apex for the anterolateral (p less than 0.01) and posterior wall (p less than 0.02) and the septum (p less than 0.02). Such a uniform gradient of end-systolic wall thickness was not present in hearts with dilated cardiomyopathy. It was even reversed for the anterolateral wall with decreasing thickness from base to apex (p less than 0.03). Left ventricular mean systolic wall thickening increased progressively from base to apex (p less than 0.005) in normal hearts, whereas there was no significant gradient from base to apex in hearts with dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220015 TI - [Thrombolysis therapy and coronary angiography in acute myocardial infarct in the Augsburg region: results of the Augsburger Heart infarct register 1985-1987]. AB - In the years 1985-87, the Augsburg Coronary Event Register registered 1333 hospitalized patients who had survived an acute myocardial infarction (AMI) for at least 24 h. In 953 patients, data on time intervals in the prehospital phase were documented in addition to the medical records data in a standardized nurse interview. The time from onset of AMI until the patient called for medical attention constituted most of the prehospital time delay. Of the interviewed male and female patients, 67% were hospitalized within 6 h (= time limit). The differences, both in the number of thrombolyses and the number of coronary angiographies performed in men and in women are statistically significant. Thrombolysis was performed in 27% of the male and 12% of the female AMI patients who were admitted to hospital within the time limit. The rate of thrombolytic therapy decreased with increasing age and was less in patients with recurrent AMI (men: 20%, women: 0%) than in patients with first AMI (men: 29%, women: 15%). There was some time-of-day variation in the percentage of thrombolytic therapy which may be attributable to hospital organization. From 1985 to 1987, the coronary angiography rates performed in the medical center doubled, independent of the thrombolytic therapy rates. In this time, angiography rates in thrombolyzed patients increased from 49% to 75%, and from 14% to 31% in patients without thrombolysis. The 28-day case fatality was 4.8% in patients with thrombolysis and 13% in patients without thrombolytic therapy. Controlling for age, sex, and recurrent AMI, this difference is not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220016 TI - [Diagnosis of ventricular septum rupture following acute myocardial infarct using a fiber-optic indwelling catheter]. AB - Rupture of the ventricular septum is a rare complication of acute myocardial infarction. Time of diagnosis, hemodynamic condition, as well as duration and effectiveness of the preoperative treatment determine the clinical outcome after surgical repair. Since its introduction the bedside-applied Swan-Ganz catheter has maintained an important role for the rapid confirmation and quantitation of the infarct-induced ventricular septal rupture. We report on the clinical courses of two patients whose diagnoses were established by means of a fiberoptic-armed Swan-Ganz catheter. Accuracy of the measured oxygen saturation was controlled by in vitro gas analyses with heparinized blood samples. As compared to conventional methods the continuous in vivo oximetry by a fiber-optic system is a simple procedure which facilitates repeated shunt calculations during hemodynamic monitoring in critically ill patients. PMID- 2220018 TI - [Abstracts of the autumn meeting of the German Society for Heart and Circulatory Research. 4-6 October 1990, Gottingen]. PMID- 2220017 TI - [Dilated myocardial disease as sequela of chronic Lyme carditis]. AB - A report is given on a 39-year-old man, who developed, after a tick bite, erythema, progressing symptoms and, after 3 years, showed the typical clinical and echocardiographic signs of a dilative cardiomyopathy. A serological test for Lyme Borreliosis was positive. Most of the symptoms disappeared after high-dose penicillin therapy. PMID- 2220019 TI - [Professor Dr. Zdenek Frankenberger, founder and first head of the Histological Embryological Institute of the Medical Faculty of Komensky University in Bratislava]. PMID- 2220020 TI - Intermediate cell tumour of the pancreas in rat. AB - A malignant tumour of the rat pancreas with features of both acinar and endocrine cells is presented. This consisted of a continuous cytoplasmic mass with numerous dispersed nuclei and branches protruding from its borders invading the surrounding exocrine tissue. The most prominent characteristic of the tumour was the co-existence of zymogen and endocrine secretory granules and cytoplasmic organelles typical of both acinar and islet cells. Some hypotheses are put forward concerning the origin of the tumour and its vasculature. PMID- 2220022 TI - Ultrastructural studies on the placentae of streptozotocin induced maternal diabetes in the rat. AB - Following induction of diabetes by a single injection of (IP) streptozotocin (STZ) to pregnant Wistar rats on days 2, 4 and 6 to 12 of gestation, fetuses and placentae were collected on day 20. The controls were either untreated or vehicle treated; alternatively following STZ injection, 2-6 IU of insulin was administered (sc) daily until term. The placentae were fixed in a glutaraldehyde and paraformaldehyde mixture and ultrathin sections were examined under the electron microscope. The structure of the vehicle treated control resembled that of the untreated control. The insulin control group had pathological changes similar to those of the diabetic group but with considerably less frequency. The giant cells in the basal zone of STZ group were numerous; they had abundant dilated cisternae of rough endoplasmic reticulum, intracytoplasmic fibrinoid and nuclear inclusions. The trophospongial cells presented numerous clear vacuoles, lysosomes and myelin bodies. Enlarged vacuoles often impinged deeply on the nucleus. The glycogen cells disintegrated resulting in cyst formation. In the labyrinthine zone, layer I trophoblast revealed increased number of large pores through which layer II trophoblast projected into the maternal sinusoid. Layer II had abundant glycogen, lipid droplets and lysosomes. Layer III had imbibed much fluid and appeared foamy with swollen organelles. Fibrinoid substance was produced by the giant cells, basophils and the trophoblast bordering the maternal sinusoids. Cyst development was preceded by degeneration of glycogen cells in the basal zone and of the trophoblast in the labyrinthine zone. Pronounced development of gonadotropin/somatotropin granule-like 'secretory granules' and smooth endoplasmic reticulum associated lipid droplets also characterised the labyrinthine trophoblast. The observed placental pathology appears to correlate well with the intrauterine growth retardation and fetal malformations recorded in this animal model. PMID- 2220021 TI - The capsule structure of Pacinian corpuscles from the cat mesentery. AB - Using the electronograms of Pacinian corpuscle capsule of the cat mesentery the authors have studied in details the structure of its layers and lamellae. The thickness of the capsule lamellae ranged between 30 nm-320 nm, the mean width being 150 nm. On the surface they are overlaid by means of lamina basalis. The capsule is formed by circular layers composed, most often, by 1-2 lamellae, less frequently, by larger number of lamellae. The width of the space between the layers of lamellae is 150-820 nm. A number of lamellae is provided with longer or shorter processes. They are directed more often to the adjacent lamella with which they can be also connected by means of membrane specialization. However, they are also directed into the space between individual layers of the capsule. The importance of these processes has not been known. Furthermore, the authors have studied the reciprocal link-up of the lamellae within one layer. The lamellae are connected either side-to-side, by inserting the end of one lamella into the infolding of the other, end-to-side or end-to-end. Rich pinocytotic activity (rich occurrence of caveolae) was observed in the lamellae of the capsule. Therefore the authors are of the opinion that the capsule and its lamellae have not only mechanical significance or the function of the transfer system and filter, but they form an important component (subsystem) of the whole metabolic system in the sensory corpuscle. PMID- 2220023 TI - Ultrastructural aspects of and observations on the permeability of the rat mesentery to colloidal iron. AB - In works already published, it was made clear that many researches were interested in the absorption phenomena, permeability and structure of the visceral mesothelial tissue. Attention was concentrated on the mesentery and observations were made using the application of lanthanum nitrate and osmium amine. The penetration of lanthanum nitrate is impeded by the basement membrane situated between the connective and mesothelial tissues. The heavy salt moves through and not between the mesothelial cells by passive diffusion. No reaction was observed in general with osmium-amine, with the exception of a few cases. In those instances, the osmium-amine reacted not only in the outer surface of the mesentery, but also penetrated with no visible reaction all the way to the connective tissue where it was detected in the elastic layer. In this paper, the colloidal iron was employed using different techniques, and depositions were detected in the surface of the mesentery, in the mesothelial cells and also in the connective tissue. A final conclusion that the permeability of different layers of tissues is of great variety and has a definite capacity for selectivity is suggested. PMID- 2220024 TI - Use of prostaglandin inhibitor, 2-(6-methoxy-2-naphthyl) propionic acid,with regard to morphological and enzymatic changes of gastric mucosa. AB - 2-(6-methoxy-2-naphthyl) propionic acid is introduced to treatment as non-steroid antiinflammatory drug (NSAID) under the trade-mark of Naprosyn. Inhibition of prostaglandin synthesis is regarded as the most likely mechanism of its action. In some patients, its side-effects include gastritis, reactivation of ulcerous niche, and upper gastrointestinal haemorrhage. The absence of complex studies addressed to the question of morphological and histochemical changes in gastric mucosa after oral administration of Naprosyn prompted our undertaking. In experimental animals, with varying doses (10 mg/kg and 50 mg/kg) and variously long administrations (1 week and 3 weeks), a trial has been reported here upon. In the frozen-sectioned preparations, the histochemical reaction for acid phosphatase activity, according to Gomori, was made. The paraffin sections were subjected to the HE staining, PAS staining according to McManus and with the Masson's method. Our results of the morphological and histochemical studies in rats support the clinical observations of mucosal destruction in stomach in patients after oral administration of Naprosyn. PMID- 2220025 TI - The effect of progesterone and progesterone + estradiol on the morphology of the pineal gland in immature female pigs. AB - Pineal gland of the immature female pigs treated with progesterone and progesterone and estradiol simultaneously were investigated with light and electron microscopy. Both of the applied hormones influenced the structure of the pineal glands. Inhibitory effect of progesterone on the relative volume of mitochondria, granular vesicles and dense bodies of type one was observed. Administration of progesterone and estradiol simultaneously caused more complicated influence statistically significant increase of pinealocyte nuclei volume and at the same time significant decrease of mitochondria and granular vesicles. PMID- 2220026 TI - Electron microscopic observations on the effect of gossypol on rat cauda epididymis. AB - Gossypol administered orally to male rats at a daily dose of 20 mg/kg body weight for 63 days caused hypertrophy of the cauda epididymal epithelium, with more than fourfold increase in height of the cells. The principal cells lost most of their microvilli and formed apical blebs which appeared to produce the dense secretory material which was found in the lumen. Less dramatic but similar changes also occurred after 9 days on the same regimen, with the height of the epithelium doubling. However after 19 days on this regimen, with the height of the epithelium doubling. However after 19 days on this regimen, the epithelium looked fairly normal apart from a maintained hypertrophy. As reported in other studies, the cauda epididymal sperm were severely damaged and immotile; many were decapitated and the oxygen uptake was low. Ultrastructural defects were abnormal or absent mitochondria, absence of plasma membranes and axonemal components and accessory fibres. PMID- 2220028 TI - Superficial and deep blood vessel distribution in the frog telencephalon. Reference to morphological brain asymmetries. AB - Nine frogs of the species "Rana esculenta" were heart perfused with Microfile Silicone Rubber. The frogs were examined both after dissection (cut with a razor blade) to study the superficial blood vessel pattern, and histologically (the Nissl staining method) to study the distribution of the deep blood capillaries. While the superficial blood vary in pattern, the deep capillaries are distributed symmetrically. This finding does not support a correlation between blood vessel pattern and morphological brain asymmetry, at least in the frog, and thus other explanations must be sought to explain brain asymmetry. PMID- 2220027 TI - An ultrastructural study on gastric endocrine cells in the stomach gland patch of the koala Phascolarctos cinereus. AB - The endocrine cells in the stomach gland patch of the koala (Phascolarctos cinereus) were studied ultrastructurally. They were classified into 3 types based on the ultrastructural profiles of their endocrine granules and tentatively categorized as type I, II, and III endocrine cells. Type I cells contained round granules that were for the most part larger than those observed in the other 2 cell types. The granules ranged from moderate to relatively high in electron density. Type II cells were angular in shape and characterized by the presence of granules that were polymorphous in profile. Contents of the endocrine granules in type II cells also showed a range of high to moderate electron density. Type III cells were oval or pyramidal in shape. They contained highly polymorphous granules that were round, oval, dumbbell-like or comma in shape and characterized by the presence of a clear space or halo separating the high to low electron dense core from the limiting membrane of granules. Type III cells were observed most often whereas type I and II cells were a less frequent observation. PMID- 2220030 TI - To change or not to change: is there a choice? PMID- 2220029 TI - AChE-positive innervation of the ureters, urinary bladder, and urethra in pigs. AB - Histochemical method of KARNOWSKY and ROOTS (1964) was used to discover the AChE positive nerves. These nerve fibres were found in all layers of all organs under study. The ureter was weakly innervated, while the urinary bladder and the urethra possessed strong AChE-positive innervation. AChE-positive fibres were most abundant in the bladder trigone. Muscular membrane was the best supplied layer, both in the urinary bladder and in the urethra. Part of AChE-positive nerves was connected with the blood vessels in all organs under discussion. PMID- 2220031 TI - Calcium and the kidney--from stones to molecules. AB - Shortly after the introduction of the thiazide diuretics it was noted that they lower the excretion of Ca2+ in the urine, enough so that they were introduced for the therapy of hypercalciuria in calcareous stone formers. This observation prompted us to begin a series of investigations designed to better understand the handling of Ca2+ by the kidney in general, and the effects of diuretics on Ca2+ transport in particular. Since it was already known that the excretion of Ca2+ followed closely the excretion of Na+ we postulated that the effects of diuretics are related to the shrinkage of extracellular (ECF) volume which signals the kidney to enhance filtrate absorption particularly in the proximal tubule. This we supported with studies showing that calcium excretion will return to the original elevated level, inspite of continued administration of the diuretic, if a high salt intake were allowed. We also showed the opposite, namely that hypercalciuria can be produced by mineralocorticoid administration if liberal salt intake were allowed, and is prevented by salt restriction. This latter observation antedated the clinical observation that primary aldosteronism is accompanied by hypercalciuria. These studies clearly showed the importance of ECF volume in determining urinary excretion of Ca2+. The site of action in the nephron of volume changes was thought to be the proximal convoluted tubule. Volume expansion had already been shown to depress proximal tubular absorption of Ca2+. We carried out studies using in situ micropuncture and demonstrated that ECF volume depletion caused by thiazide diuretics results in enhanced absorption in the proximal tubule confirming the suspicion that changes in ECF volume were translated into reciprocal changes in proximal tubular absorption. Meanwhile we showed that a different group of diuretics, the high-ceiling diuretics, unlike the thiazides produce a major increase in Ca2+ excretion suggesting that they exert their effects at a different site in the nephron, namely the loop of Henle. These and many other studies dictated that we examine more directly the handling of Ca2+ by the kidney, and for that purpose we employed the technic of in vitro microperfusion of isolated renal tubule segments. In the S2 segment of the proximal convoluted tubule we were able to show that Ca2+ absorption was entirely passive, following the electrochemical gradient for calcium present in this segment (luminal PD positive, tubular fluid [Ca2+] greater than plasma [Ca2+]).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2220032 TI - [Metabolic diseases: a challenge for pediatrics]. AB - During the past ten years we have identified in five girls a previously unreported hereditary metabolic disease with severe neurologic involvement. A common defect in the carbohydrate structure of serum glycoproteins could be demonstrated. This disease illustrates the great challenge that metabolic diseases are for pediatrics. Their number is very large and increases steadily; most of them can not yet be treated efficiently, and nearly all these disorders are hereditary. These and other features make a national and international approach necessary. PMID- 2220033 TI - [Problems of the preparation and control of properties of sterile drug-containing liposomes]. AB - The techniques employed to produce drug-containing liposomes and to control the disperse composition of the included preparation are discussed. The method of cryoradiation sterilization of liposomes containing different types of drugs is detailed. The applications of the described methodologies for obtaining the optimal technological parameters of liposome production are exemplified. PMID- 2220036 TI - [All-Union program "Liposomes and their use in biology and medicine" (the research and research-practice parts of the program)]. PMID- 2220035 TI - [Effect of the liposomal preparation aminophosphatide on erythrocyte lysis]. PMID- 2220034 TI - [Effect of subcutaneous administration of liposomes on the functional state of the organs and systems in experimental animals]. AB - Based on the study of subcutaneous injection of lecithin-cholesterol liposomes, its possible toxic effect is discussed and the effect threshold is determined. It is shown, that long-term subcutaneous liposome administration is attended with hepatic cell damage. One or two injections of the preparation does not cause a toxic lesion of the viscera and may be used for therapeutic purposes. A considerable threshold-subthreshold dosage range allows for vast variability of administered liposome amounts. PMID- 2220037 TI - [Ectericide as a dispersion medium for the preparation of prospective clinical liposomal drug forms]. AB - The possibility of using ectericide, having antibacterial, detergent, antioxidative, and reparative effects, as a dispersion medium for liposome production has been studied. Its application allows for elaboration of a simplified liposome production technique simultaneously imparting them stability against oxidation, heating, and pH changes. A technology to produce multivesicular liposomes with ectericide++, containing rifampicin in the membranous envelope and gentamicin in the inner volume, has been developed. Liposomal antibiotics proved to be effective in clinical trials. PMID- 2220038 TI - [Anti-inflammatory effects of liposomes]. AB - Studies of antiexudative, antialterative, and antibacterial effects of lecithin cholesterol liposomes suggest their possible use as antiinflammatory agents. It is shown that incubation of liposomes with opportunistic microorganisms is attended with a pronounced antibacterial effect, while subcutaneous injection of liposomes significantly reduces the soft tissue edema caused by administration of formalin, and prevents pronounced alteration in response to acetic acid solution. A conclusion is derived on the possibility to use the membranotropic properties of liposomal membranes to alleviate manifestations of inflammation. PMID- 2220039 TI - [Biological effect of liposomes in hypoxic conditions of various etiologies]. AB - The antihypoxic and antioxidative effects of phosphatidyl choline liposomes have been studied in hypoxic hypoxia, pneumonia, and acute blood loss. It was demonstrated that the body tolerance of persisting hypoxia increased on liposome administration due to elimination of lactate-acidosis, inhibition of lipid peroxidation and higher rate of oxygen diffusion through the biological barriers. The antihypoxic properties of the vesicles are determined by their remedial effect on the key mechanisms responsible for the development of hypoxic organ damage. PMID- 2220040 TI - [The first results and objectives of the study of Lyme disease in the USSR]. AB - Results of research on the prevalence, etiology, laboratory diagnosis, epidemiology, epizootology, and other aspects of Lyme's disease, which was initiated in this country in 1984, are summed up. This Borrelia-caused condition is now suggested to be a lead in morbidity rate among human diseases of natural nidus. The most topical, priority directions of further research are discussed. PMID- 2220041 TI - [Molecular mechanisms of the effect of estradiol (the latest concept)]. PMID- 2220042 TI - [Methodology of the branch program in traumatology and orthopedics in present-day conditions]. AB - The method of targeted programming is just entering the practice of science planning in traumatology and orthopedics as specific branch-oriented scientific and technological programmes. The essence of the methodological maintenance of Programme C.18 is presented; the Programme is aimed at elaborating the therapeutic system to manage patients with fractures of bones of the locomotor apparatus. Its result will present as the data on the structure of the general population of such patients, on the optimal methods of treatment, as well as on the issues of the emergency aid organization. Methods to estimate the future and current need in the traumatological-orthopaedic equipment will be elaborated. The programme is carried out according to the coordinated schedule, involving research institutes and departments of traumatology and orthopedics, the total number of the establishments amounting to 70. The programme implementation covers the period from 1986 to 1999. PMID- 2220043 TI - [Trends in the development of research in the field of liposomes (review of patent literature)]. AB - The review embraces major trends and tendencies in liposome studies and is based on the statistical and qualitative analysis of patent information issued in the period 1970-1988. Special attention is devoted to the analysis of patents in liposome production techniques, their lipid composition, and application in pharmaceutical and cosmetic industries and also for the diagnostic and therapeutic purposes. Liposomal preparations are shown to be superior to common drugs as concerns, in particular, liposomes containing medicinal agents for prolonged use (including hormones, antibiotics, cytostatics, and immunostimulants) and liposomes used in dermatological practice. Liposome-based assessment of application prospects is given. PMID- 2220044 TI - [Abortion as a high risk factor in perinatal pathology]. AB - Analysis of the pregnancy course and neonatal outcomes in 896 women with a history of recurrent spontaneous abortion showed a high rate of perinatal disease and neonatal problems. This is underlain by hormonal, immunological, and some other disorders, and also by a high infection level both during pregnancy and without it. To reduce the perinatal morbidity rate, a system of the reproductive function check-up and rehabilitation for the non-pregnant and a stage-by-stage control over the pregnancy course and the status of the fetoplacental unit was suggested. PMID- 2220045 TI - [Rational tactics in the management of pregnancy and labor to prevent perinatal morbidity and mortality]. AB - Results of a cooperative multicenter research have shown that extended studies into scientifically based and regionalized diagnostic screening programmes aimed at sequential follow-up of the gestational phases and early detection of complications is a means to reduce perinatal morbidity and mortality. These programmes should be based on the population characteristics of the fetal and neonatal growth as well as on the incidence and pattern of perinatal disease with consideration of the region-specific birth rates. An adequate range of diagnostic tests provides comprehensive information on intrauterine growth disturbances and allows for finding the criteria for pregnancy prolongation, a complex of intensive therapy steps, and modes of elective delivery together with indications for it. PMID- 2220046 TI - [Effect of ecological factors on the course of pregnancy]. AB - Results of the studies dealing with the peculiarities and mechanisms of abnormal pregnancy in women working under unfavourable environmental factors are overviewed, including the diseases most commonly complicating the gestational course in female workers of chemical and electronic industries, patterns of pregnancy complications, and immunological mechanisms of placental damage under chemical aggression. Data are given on the fetal functional status derangement under the environmental stress. The concept of a three-stage adaptation of the female organism to the environmental hazards is introduced, and priorities are formulated relating to the control of environmental impacts on gestation, female fertility, and fetal and neonatal health. PMID- 2220047 TI - [Occupational hazards as risk factors of perinatal pathology]. AB - Occupational hazards play the leading role among the factors responsible for perinatal disease, increased morbidity and mortality of neonates and infants of the first year of life. These factors are deleterious to the female organism both prior to and during pregnancy, they may exert an unfavourable effect on the fetus, and impair the general health status of future mothers by affecting the functioning of separate organs and body systems, triggering metabolic disorders, and reducing body defence. Studies conducted by experts in labour hygiene, obstetricians-gynecologists, and pediatricians yielded results that formed the basis for prevention planning aimed at health promotion effect. PMID- 2220048 TI - [Group B streptococci in neonatal pathology: pathogenetic mechanism, diagnosis and prevention]. AB - Group B streptococci have recently attracted the attention of researchers as the causative agents of human neonatal disease. They are currently encountered much more frequently than it was believed previously. Various types of adult pathogen carriers have been described; this accounts for the numerous sources and pathways of infection transmission, both vertical and horizontal. The transmission risk depends on many factors, vaginal colonization in the parturient being of special import. The level of the pathogen adhesion to the barrier epithelium is reflective of the tissue sensitivity to infection. Increased sensitivity of the vaginal epithelium to B streptococci adhesion in association with the intake of some contraceptives has been found. The adhesive activity of avirulent streptococci B strains is shown to be higher than in the virulent strains, which is especially important in mixed virus bacterial infections. The streptococcal infection of high mortality is underlain by activation of persisting avirulent streptococci B that manifest their pathogenicity as a result of the virus specific modifications in the host cell membrane. During 1985-1987, in Leningrad Institute of Gynecology and Obstetrics over 80 strains of streptococci B were isolated, the leading serotypes being Ia/C, Ib/C, II/C, III/R. Only 54% of the studied pregnancies attended with the streptococcus carriage had a favourable neonatal outcome. The strain serotypes from maternal isolates and abortuses fully correlated. Further improvement of the laboratory diagnosis and means of the pathogen and its carriers identification is a current priority. PMID- 2220049 TI - [Medical aspects of reducing perinatal mortality and perinatal morbidity]. PMID- 2220050 TI - [Diagnosis of chronic fetal anoxia]. AB - The intrauterine fetal status was assessed in women at 34-42 week gestation; the pregnancies were complicated by obstetric and extragenital disease (nephropathy, prolonged gestation, hypertension, diabetes mellitus, renal disease). Computer assisted analysis of the diagnostic value of fetal cardiotocography, uterine placental hemodynamics, and acid-base status of maternal capillary blood showed that the following parameters are most informative for the diagnosis of chronic fetal hypoxia: stable rhythm duration; oscillation amplitude; acceleration/deceleration number, amplitude, and duration; volume flow rate of the uterine-placental unit; and pH and base deficiency in the blood taken from the cervix uteri. PMID- 2220051 TI - [Protection of the developing brain--the most important task of perinatal medicine]. PMID- 2220052 TI - [Autonomic and visceral disorders in perinatal encephalopathy]. AB - The prevalence of perinatal encephalopathy is shown to be significantly increased. This pathology is associated with involvement of the brain and spinal cord and the whole organism with subsequent development of cerebral dysfunction and somatic disease. Medicamentous therapy is aimed at improving the trophics of the damaged tissues and elimination of edema. The role played by the district pediatrician in the follow-up of children with the discussed disease is considered to be of special significance. PMID- 2220053 TI - [Respiratory distress syndrome in newborn infants]. PMID- 2220055 TI - [Can medical research institutes take advantage of a new economic system?]. PMID- 2220054 TI - [Use of human immunoglobulin in infectious and inflammatory diseases of premature infants]. PMID- 2220056 TI - [The ultrastructure of epithelioid cells in sarcoidosis and sarcoid reactions]. AB - Electron microscopic examination of epithelioid-cell granulomas of two patients with total sarcoidosis and of three ones with isolated sarcoidosis of the skin (sarcoid reactions) has revealed a morphologic polarization of epithelioid cells, manifesting as 4 zones: (1) crimped [correction of chimp] edge zone, (2) zone of vesicles and vacuoles, (3) basal zone, (4) osmiophilic granules zone. The structure of epithelioid cells in sarcoidosis and in sarcoid reactions was found similar, evidencing a high biosynthetic function of the cells. PMID- 2220057 TI - [The clinical and serological characteristics of early congenital syphilis today. 1]. AB - The results of examinations of 210 infants with early congenital syphilis with emphasis on skin involvement are analyzed. An increased incidence of syphilitic pemphigus was recorded along with decreased incidence of diffuse infiltration and papular elements. PMID- 2220058 TI - [Devergie's lichen ruber pilaris]. PMID- 2220059 TI - [Systemic antimycotics in the therapy of patients with foot mycoses]. PMID- 2220060 TI - [Mixed bacterial and viral infections of the urogenital tract]. PMID- 2220061 TI - [Metabolism, vascular tonus and the bone-joint system of psoriasis patients]. AB - A total of 113 patients with disseminated psoriasis were examined. Roentgenograms of the joints have shown signs of osteoarthrosis deformans in 85.7 percent of them. Involvement of the joints of the soles was recorded in 80.5 percent, of the hands in 58.3 percent, of iliosacral articulation in 33.3 percent of patients. These shifts were in line with clinico-laboratory changes characteristic of psoriatic arthropathy in less than one third of the examinees. Rheovasography of the upper and lower limbs has revealed the spastic asthenic syndrome in all the examinees; this syndrome most frequently manifested by increased tone and decreased pulse blood content of the vessels. A direct correlation between x-ray changes in the joints and disordered vascular tone of the limbs has been revealed. The detected elevation of blood lipid level in psoriasis patients as a rule did not correlate with impaired blood supply to the upper and lower limbs. These findings bring the authors to a conclusion that in psoriasis not only the skin, but the bone-and-joint and vascular systems are involved in the process, as are the metabolic processes. PMID- 2220062 TI - [The morphofunctional characteristics of the peripheral lymph nodes in patients with chronic pyoderma]. AB - Pathohistologic examinations of the peripheral lymph nodes in 14 patients with abscessed acne, chronic infiltrative ulcerous and infiltrative fistulous pyoderma coursing for 1 to 11 years have revealed that chronic pyococcal infection induces manifest atrophic and sclerotic changes in the cortical and medullary layers of the regional lymph nodes and of those distant from foci of involvement; these changes are accompanied by essential impairments of the immunologic, lymphopoietic, and other functions. PMID- 2220063 TI - [The immunological indices of the blood serum and saliva in children with psoriasis]. AB - Blood serum and salivary characteristics of immunobiologic reactivity were examined in children suffering from psoriasis. Increased blood serum levels of IgG and lowered IgM were detected. Lysozyme and complement levels were increased both in the blood serum and saliva. PMID- 2220064 TI - [The rate of detecting Chlamydia in male homosexuals with syphilis]. AB - A total of 159 homosexuals suffering from various forms of syphilis, aged 17 to 71, were screened for chlamydial antigen with the use of fluorescent monoclonal antibodies. Asymptomatic urogenital chlamydiosis was detected in 33 of 107 (30.8 percent) homosexual syphilitics. In 52 patients the material was collected simultaneously from the throat, urethra, and rectum; Chlamydia were detected in 71.2 percent of these. PMID- 2220065 TI - [Experience in treating chronic urethritis in men by iontophoresis and inductothermy]. AB - A method for therapy of chronic urethritis by exposure to ionized solutions of drugs has been developed (Authors' Certificate of the USSR No. 876138). Active electrode is placed in the flask with the drug, passive one on the external surface of the body as close to the focus of involvement as possible. Ionized solution of the drug (2.5-3.1) is introduced into the urethra via a double-lumen catheter, washes its walls and saturates the mucosa; the solution is aspirated from the urethra through the other lumen of the catheter, thus removing the inflammation products from the urethra. Current density has made up 0.01-0.03 mA/cm2, length of session 12-15 min, 6-8 sessions per course. A device for local therapy of chronic urethritis by a combination of ionophoresis and inductothermy has been suggested (Authors' Certificate of the USSR No. 1084031). This device permits a simultaneous administration of 2 drugs: one from the tube via urethral mucosa, the other from the cuvette outwardly. Current density has made up 0.01 0.03 mA/cm2, with the current of 200 mA in the inductor. Length of inductometry and ionophoresis session is 10-15 min. PMID- 2220067 TI - [Monilethrix in 3 generations]. AB - Monilethrix, a kind of hair aplasia, is described in patients belonging to three generations. An original treatment scheme used is described. PMID- 2220066 TI - [Early congenital lymphedema of the lower extremities combined with pachyonychia]. AB - A four-year-old girl with early congenital lymphedema of the lower limbs in combination with the nail plate involvement (pachyonychia) is described. Such a combination is not characteristic of early lymphedema, it is usually described in late edema of the lower limbs. The described case was a sporadic one in the family. It cannot be excluded that lymphedema development was induced by impaired embryogenesis of the lymph vessels resultant from sulphanilamides intake for severe bronchitis that proband's mother had suffered during pregnancy. PMID- 2220069 TI - [The clinico-morphological diagnosis of cancer of the sweat glands]. AB - Comprehensive clinical, morphologic, and ultrastructural studies of 12 cases with various forms of carcinoma of the sweat glands permitted distinguishing the clinical nodular and papular-cystic forms. Histologically malignant analogs of benign tumors, primary adenocarcinomas, and unclassified tumors are distinguished. The histogenetic appurtenance of the tumors of the latter group may be identified only by ultrastructural studies that help detect a number of organ specificity signs. Electron microscopy used in the diagnosis of poorly differentiated tumors of the skin helps carry out adequate therapeutic strategy and permitted a better validated prediction. PMID- 2220068 TI - [The metronidazole treatment of vaginitis patients]. PMID- 2220070 TI - The polypeptide composition of vaccinia-infected cell membranes and rifampicin bodies. AB - The protein and glycoprotein composition of a sucrose gradient fraction from vaccinia infected cells treated with rifampicin was studied. This particulate fraction contained cytoplasmic membranes and pleomorphic membranous structures. The glycoproteins (89, 42 and 20-23 kDa, respectively) were identified as the same glycoproteins that are found in plasma membranes of infected cells and the envelope of extracellular enveloped vaccinia (EEV). These glycoproteins could be solubilized by 0.1% NP-40. The Golgi membrane associated 41K acylated vaccinia protein was also NP-40 soluble. In contrast, most particulate fraction proteins (125, 100, 86, 65, 41, 39, 31, 27, 25, 14 and 12.5 kDa) with the exception of the 33 and 29 kDa proteins remained essentially insoluble after NP-40 treatment. The 86 and 65 kDa proteins are the rifampicin inhibited precursors to INV core proteins while the 33 and 29 kDa proteins are INV surface proteins. Twelve proteins behaved like their respective comigrating INV proteins when extracted with NP-40 and 2ME. Electron microscopy showed that a centrifuged sediment from NP-40 treated cells contained pleomorphic protein containing membranous structures that we have called rifampicin bodies. We conclude that (1) the major glycoproteins found in the particulate fraction from sucrose gradients are vaccinia glycoproteins residing in cytoplasmic membranes while (2) the major non glycosylated proteins are components of the rifampicin bodies and that (3) the rifampicin bodies represent an intermediate in the morphogenetic process leading to mature INV. PMID- 2220071 TI - Serological analysis of duck hepatitis B virus infection. AB - A radioimmunoassay was developed to detect duck hepatitis B virus surface antigen and antibody; viraemia (DHBV DNA or DHBsAg) was detected in all ducks inoculated within 3 weeks post-hatch, and persistent infection developed in 93% of birds in this group. In contrast, only 80% and 60% of ducks inoculated 4- and 6-weeks post hatch respectively developed viraemia, and approximately 70% of the viraemic ducks became carriers. Markers of viraemia were undetected in ducks inoculated 8 weeks post-hatch and in uninfected controls. A typical anti-DHBs seroconversion developed subsequently in 2 of 4 birds that showed transient viraemia, and antibody also developed in 3 of 7 ducks inoculated 4-8 weeks post-hatch that showed no viraemia. However, gene amplification by the polymerase chain reaction demonstrated DHBV DNA in ducks from the latter group suggesting that the antibody did not result from passive vaccination. Thus, increased resistance to infection develops with increasing age that may be related to several factors including host immunity. This model may help elucidate similar age-related features of human hepatitis B virus infections. PMID- 2220072 TI - Yeast Saccharomyces cerevisiae selectable markers in pUC18 polylinkers. PMID- 2220073 TI - The chromosomal constitution of wine strains of Saccharomyces cerevisiae. AB - A general procedure is described for determining the chromosomal constitution of industrial strains of Saccharomyces cerevisiae based on analysis of segregation frequencies for input markers among random spore progeny of industrial-laboratory strain hybrids. The multiply auxotrophic haploid testers used carried a dominant erythromycin-resistance marker, allowing hybrids to be selected in mass matings with spores produced by the wild-type industrial strains. Analysis of a number of independent crosses between the haploid testers and an unselected population of spores of each wine strain distinguished between disomic, trisomic and tetrasomic chromosomal complements in the parents. Possible explanations for a significant class of aberrant segregation frequencies are discussed. Results of the analysis indicate that UCD Enology 522 (Montrachet) is diploid and possibly trisomic for chromosome VII; 522X is diploid; UCD Enology 505 (California Champagne) is disomic for chromosome XVI, trisomic for chromosomes I, II, III, VI, VIII, IX, X, XII, XV, tetrasomic for chromosomes IV, XI, XIII, XIV and either trisomic or tetrasomic for chromosomes V and VII; and that UCD Enology 595 (Pasteur Champagne) is disomic for chromosomes I, II, III, IX, XVI, trisomic for chromosomes IV, VI, X, XII, XIV, XV, tetrasomic for chromosomes V, VIII, XI, XIII and either disomic or tetrasomic for chromosome VII. PMID- 2220074 TI - Chromosome III of Saccharomyces cerevisiae: an ordered clone bank, a detailed restriction map and analysis of transcripts suggest the presence of 160 genes. AB - Using lambda phage vector EMBL4, we isolated 344 clones containing segments of chromosome III of Saccharomyces cerevisiae, analysed their physical structure with eight restriction enzymes and sorted the data in contiguous groups with computer programmes. Furthermore, we performed Southern hybridizations between the sorted contiguous clone groups and interrelated them into larger groups. In this way, we constructed an ordered clone bank that covers almost the whole of chromosome III with a single gap of several kilobases in length. The consensus physical map thus obtained totals 334.6 kb, which is in good agreement with the size of this chromosome estimated by pulsed-field gel electrophoresis. Southern hybridization analysis with the DNA probes containing telomere-specific sequences showed that the bank contained a telomere at a position corresponding to the right arm terminus of chromosome III. Also, five Ty elements were found to be present. To estimate the number of genes on this chromosome and to analyse their levels of expression, we performed a series of Northern hybridization experiments using total poly(A)+ RNA from vegetatively growing cells and appropriate restriction enzyme fragments from the bank. Thus, we identified a total of 156 transcripts on chromosome III, indicating, on an average, one gene in every 2 kb on this chromosome. The transcripts were visually categorized into five groups according to their apparent levels of expression. It was found that the genes located near both termini are expressed only at low levels and that highly expressed genes are rather scattered over the chromosome. PMID- 2220075 TI - Mapping of the trifunctional fatty acid synthetase gene FAS2 on chromosome XVI of Saccharomyces cerevisiae. AB - The trifunctional FAS2 gene encoding subunit alpha of the Saccharomyces cerevisiae fatty acid synthetase complex was mapped on the left arm of chromosome XVI 24 centimorgans proximal to GAL4 and 39 centimorgans distal to PEP4 relative to the centromere. Mapping was achieved by three independent methods: meiotic co segregation of FAS2 and ARO7 in recombination-deficient spo11-mutants: tetrad analysis of crosses between FAS2, GAL4 and PEP4; and Southern hybridization of purified FAS2 DNA with individual yeast chromosomes separated by pulsed-field gel electrophoresis. PMID- 2220076 TI - Mating type locus-dependent stability of the Kluyveromyces linear pGKL plasmids in Saccharomyces cerevisiae. AB - The linear killer plasmids, pGKL1 and pGKL2, from Kluyveromyces lactis stably replicated in mitochondrial DNA-deficient (rho 0) MATa or MAT alpha haploids of Saccharomyces cerevisiae, but were unstable and frequently lost in rho 0 MATa/MAT alpha diploids, suggesting that the replication of pGKL plasmids was under the control of the MAT locus. In MATa/MAT alpha cells of S. cerevisiae, the MAT alpha gene product (alpha 2) is combined with the MATa gene product (a1) and the resultant protein, a1-alpha 2, acts to repress the expression of haploid specific genes. Experiments showed that the K. lactis linear plasmids were stably maintained in rho 0 mata1/MAT alpha diploids, indicating that the a1-alpha 2 repressor interfered with the stability of pGKL2. It was revealed by computer analysis that the consensus sequence homologous to the a1-alpha 2 repressor binding site occurred within the coding regions of pGKL2 genes which were presumed to be essential for the plasmid replication. Since the plasmids were stably maintained in diploids of K. lactis, the mating type control must not be working there. PMID- 2220077 TI - The omnipotent suppressor SUP45 affects nucleic acid metabolism and mitochondrial structure. AB - Yeast (Saccharomyces cerevisiae) strains sensitive to a variety of drugs were used to select for novobiocin-resistant mutants that were simultaneously temperature-sensitive. The mutants remained as sensitive as the parent strains to a wide range of drugs other than novobiocin, and did not exhibit any suppression of suppressible auxotrophic markers. At the non-permissive temperature, the mutant cells arrested mainly as unbudded cells, and were instantly defective in DNA and RNA synthesis, but not protein synthesis. The cloned wild-type gene was identified as SUP45, which has been previously implicated in the translation process. Our results suggest that SUP45 may have a function in addition to, or different from, the one that has been assigned to it previously. PMID- 2220078 TI - The yeast regulatory gene PHO4 encodes a helix-loop-helix motif. AB - Evidence is presented, based on sequence comparisons and secondary structure prediction, of the presence of a DNA-binding and dimerization helix-loop-helix motif in the yeast transcription activator PHO4. Interest in the existence of this first known motif in yeast is discussed. PMID- 2220079 TI - Development of rancidity in salmonoid steaks during retail display. A comparison of practical storage life of wild salmon and farmed rainbow trout. AB - The quality of wild salmon and farmed rainbow trout from aquaculture, both packed in transparent vacuum-skin packaging, was followed during storage for 6 months in an illuminated freezer cabinet (product temperature -17 degrees C, half of the packs protected against light, and half of the packs fully exposed to light), combining (a) colour determination of the carotenoid-pigment flesh by tristimulus colorimetry, (b) determination of thiobarbituric-acid-reactive substances (TBA value), (c) carotenoid analysis and, at the end of the storage experiment, (d) sensory evaluation. Rancidity developed faster in steaks of wild salmon (TBA increased during 6 months of storage from 2.8 mumols malonaldehyde/kg flesh to 12.5 mumols/kg for light-protected packages, and to 17.6 mumols/kg for packages exposed to fluorescent light) as compared to steaks of farmed rainbow trout (TBA increased from 1.2 to 5.8 mumols/kg, independent of light exposure), a finding also confirmed by sensory evaluation. In both products, the carotenoid pigment was identified as astaxanthin; salmon steaks, the product more susceptible to developing rancidity, had the lower astaxanthin content (rainbow trout 9.1 mg/kg flesh, salmon 4.9 mg/kg, prior to storage). While the astaxanthin content remained virtually constant in salmon steaks during storage, the content decreased significantly in steaks of rainbow trout, an observation which suggests the role of astaxanthin as a sacrificial protector against radical processes. PMID- 2220080 TI - [Investigation of accuracy of fit of partial crowns with different shaped margins]. AB - The marginal adaptation of partial crowns with different types of finish line preparations was determined by means of dye penetration tests. The best marginal sealing was found for the featheredge-like preparation, followed by the shoulder preparation and the chamfer preparation with or without bevel. The scanning electron microscopic evaluation revealed that a finishing of the restoration margins during the setting of the luting material resulted in a better marginal sealing than a finishing after the cementation. PMID- 2220081 TI - [Evaluation and classification of dysfunction patients]. AB - The "Stomatognathic-Dysfunction-Index" (SDI) comprises anamnestic and clinical information regarding occlusion, TMJ, head- and neck muscles. The different SDI parameters were chosen in a way that enables them to lead to a firm statement regarding the individual dysfunction. The examination results are easily reproduceable in the sense of a "intra- and inter-examiner reliability" and the scores can be reattributed to individual combinations of symptoms. The patients can be sorted into classes of dysfunction according to their total SDI-Score. This makes the SDI especially suitable for epidemiologic studies, but the easy handling of the SDI allows its use in private practice as well. Here it enables the dentist to classify patients with stomatognathic dysfunctions according to the necessity of treatment and sometimes to determine such necessity as well. The SDI is not meant to replace the extensive standard methods of clinical and instrumental analysis. It is meant to provide a maximum of diagnostic and therapeutic economic value from an affordable input of time in the everyday routine. It fulfills all requirements of an index for epidemiological studies. PMID- 2220083 TI - [Lithiasis in small salivary ducts. Report of 3 cases]. AB - Three cases with sialolithiasis of minor salivary gland are presented. The sialoliths were found on the left side of the upper lip (two patients) with local infection and on the right side of buccal mucosa (one patient) without any symptom. The histologic findings resulted from our own cases and the etiology are discussed extensively and a literature review is made as well. PMID- 2220084 TI - [Advances in tooth root resection]. PMID- 2220082 TI - [Comparison investigation of non-precious metal-synthetic resin bond on basis of new adhesives and the non-precious metal-ceramic bond]. AB - The adhesive force was tested between the Silicoater and Sebond-MKV bonding systems and two Co Cr alloys. The tests were: The flexural strength-test, the tensile stress-test, the fracture test and the shear strength test. The ceramic veneering had worse results only in the flexural strength test compared with the two bonding systems. The bonding system Silicoater was in the tensile stress test and in the fracture test better than the Sebond MKV system. The bonding system Sebond-MKV showed better results in the flexural strength test and in the shear strength test than the Silicoater system. Differences in the results you could find between the test after dry air storing and saliva storing. PMID- 2220085 TI - [Functional value of hyperbalance for function course in temporomandibular joint]. AB - The resulting effects of excursive attrition contacts on balanced side are pointed out. In a case report new ultrasonic recordings of TMJ movements with MT 1602 system are described to demonstrate the influence of overbalanced contacts on the axiographic track of TMJ condyle. Characteristic changes of the axiographic path results and are discussed as distraction effects of TMJ condyle. PMID- 2220086 TI - [Theoretical and clinical aspects of guide plane in crown and bridge prosthetics]. PMID- 2220087 TI - [Musculature in dentistry]. PMID- 2220088 TI - [Is the telescope system still reasonable?]. AB - Parallel milled abutments in partial dentures are the anchors of the so called telescoping system. Excellent function, easy cleaning and the possibility of modification on the case at a later date - if further losses of teeth should occur - are the great advantages of this design. The application of this suitable attachment seems to be limited by economic considerations and patients' desire for fixed brigdework. The state of the art is presented and proved by pretentious case-reports. PMID- 2220089 TI - [Follow-up study of accuracy of fit of crowns, prepared for phantom head under practice conditions]. AB - Mesial, distal, oral and vestibular measurement of fissure spaces in 39 crowns and 51 bridges (divided with interlock-connection) made in the context of propedeutic instruction showed a mean marginal discrepancy of 62-90 microns in a range of 30-160 microns. A simple method to evaluate the fissure space was described. In actually discussion the results would be helpful to determine criterions for quality on fixed restorations. PMID- 2220090 TI - [Perspectives of a function study of the TMJ with magnetic resonance imaging]. AB - Magnetic resonance imaging of the temporomandibular joint is usefull in the examination of the stomatognathic system. In order to visualize the components of the temporomandibular joint during dynamic jaw movement and to improve the diagnostic accuracy of temporomandibular joint disorders we present remedies for magnetic resonance imaging and discuss their possibilities and limits how you can stabilize the jaw in an interesting functional position during examination period. PMID- 2220091 TI - [Function damage of masticatory organ. Retrospective study of 1,778 patients in a West German clinic]. AB - The etiology of the TMJ dysfunction-pain syndrome is multicausal and composed of several factors which are just partly known. To get more information about etiology, diagnostic and therapeutic means, data from 1778 patients with subjective complaints of mandibular dysfunction have been analyzed. The most frequent dental findings in clinical functional analysis and psychological and social aspects are evaluated and discussed. Concepts for initial therapy are pointed out and reviewed in experience of the numerous cases. The data show that filling therapy could initiate functional disturbances which should be considered in daily practice. PMID- 2220092 TI - [Patient with high risk of caries. Definition, epidemiology and clinical aspects]. AB - Epidemiological studies have shown that there is a small group of patients with high caries prevalence. This survey illustrates the clinical picture of caries active patients on the basis of exemplary cases and defines a number of terms which are important in this context. In addition to this, possible causes of an increased caries risk are discussed. PMID- 2220093 TI - [Identification of children with high risk of caries related to caries occurrence in the past]. AB - In several studies high correlations were found when the prevalence of caries in the past was correlated with future caries risk in children and adolescents. The practical value of this method for the identification of children with high risk for caries can be assessed by measurement of the ability of the method to recognize subjects who will develop caries (sensitivity) and to exclude those who will not (specificity). Taking into consideration worldwide studies from recent years the problems of this method were pointed out and discussed. PMID- 2220094 TI - [Possibilities of assessing the individual caries risk using microbiological parameters]. AB - The most commonly used microbiological tests for identifying patients with high caries activity are based on quantitative or semi-quantitative counts of Streptococcus mutans and Lactobacilli. In a review the prognostic value of such tests is discussed and shown, that in spite of partially high prediction rates, the prognostic value of either S. mutans or Lactobacillus tests can be confirmed only in combination with additional relevant clinical parameters (e.g. anamnesis, DMF-increment, secretation rate and bufferin capacity of saliva...). PMID- 2220095 TI - [Selective intensive prophylaxis in area of group prophylaxis]. AB - An increasing polarisation of caries prevalence in children was found in recent years. A needs-related prevention programme was thus developed which provides for selective intensive treatment of pupils with increased caries risk. A corresponding prevention programme was tested at elementary schools in Gottingen in 1985-1989: whereas in 1985, 31% of the 4th-class pupils had caries-free permanent teeth, this percentage had increased to 45% in 1989. The average DMF-S was 1.9 in 1989 (1985: 3.9). PMID- 2220096 TI - [Concept for the care of caries active patients in dental practice]. AB - By help of a practical procedure the individual caries risk can be estimated. Regarding the individual caries risque and the age of the patient, therapeutical steps can be taken to reduce this risk. This concept of reducing the number of bakteries causing caries can be divided in therapeutical procedures, that can be made in the dental office and procedures, that can be made by home care. Therapeutical effects can be controlled by microbiological procedures. PMID- 2220097 TI - [Caries risk in youth from sociopsychological viewpoint]. AB - Attitudes and behavioural patterns to dental health were recorded by standardized questionings of 900 juveniles aged between 12 and 16 years. Health-related behaviour corresponds with demographic and sociopsychological factors. Education within the family is very important for the development of a healthy way of life. Experiences of juveniles with dental care essentially determine their curative and preventive compliance. Juveniles with a negative attitude towards dental health require as a potential caries risk group special attention in health advising and dental care. PMID- 2220098 TI - [Electric toothbrushes--manual toothbrushes, a comparison]. AB - This study covering a period of almost 16 weeks shows that manual tooth cleaning must be regarded as somewhat superior to electric tooth-brushes in terms of the plaque index. Concerning the more important sulcus bleeding index, the electric tooth-brush leads to better results. This, however, only after at least two weeks of "familiarisation" of the patients with the electric tooth-brush, and after a minimum follow-up time of three to five weeks! This is why another quite important conclusion should be drawn from this study: studies of this type should not be planned for too short a period, i.e. for at least 12 weeks. PMID- 2220100 TI - [Plaque reduction in patients with removable partial dentures and abutment teeth with greatly reduced periodontium]. AB - The presented investigation was carried out on 19 individuals who were referred for prothetic and periodontal treatment. All patients suffered from advanced periodontal disease and had no more than 3 teeth left in the jaw going to be treated. Following a baseline examination comprising assessment of oral hygiene and tooth mobility the patients were subjected to prothetic and periodontal treatment. Removable partial dentures were constructed using the conical crown system. The patients were distributed into 2 different maintenance groups. 10 patients (group 1) were instructed to use the Bass Technique for cleaning the remaining abutment teeth. Group 2 applied proximal brushes for cleaning the interdental spaces prior to removing the partial dentures for cleaning as prescribed for group 1. Three months after treatment a reexamination was performed. In both groups a significant reduction of plaque was observed. The plaque scores of the second group were below those of the first group but the difference was statistically not significant. PMID- 2220099 TI - [Local treatment of inflammatory changes in oral cavity with the new Dontisolon M]. PMID- 2220101 TI - [Innovative system for overlay denture therapy]. AB - The short blade-implant ist adapted to the more reduced alveolarappendage in profile too. Generally this implant means more safety for the operating dentist. A lately developed intramobile element connected with this implant provides a greater relief of the implanted. A long vertical way of replacement produces more extra safetyreserves for the effective compendation of the appearing chewing forces. The attachment can be combined with nearly all prothetical solutions. This intramobile element can be changed without any problems by the patient himself. PMID- 2220102 TI - [Endocarditis risk in use of dental irrigators]. AB - The incidence of bacteremia after application of a dental irrigator was investigated in 100 healthy volunteers. Venous blood was inoculated in routine blood culture bottles one, three and five minutes after dental irrigation. In 39 volunteers a transient bacteremia was detected, mainly Strep. Viridans was cultured. Incidence correlated with the grade of oral hygiene und periodontal disease. PMID- 2220103 TI - [Replantation]. PMID- 2220104 TI - [Determination of transverse resilience of human temporomandibular joint]. AB - Transversal TMJ-resiliency is defined as a possible movement of the condyles exclusively in the lateromedial direction. The extent of this individual and variable shifting of the condyles can be recorded and reproduced using high resolution electronic axiography and a special manipulating technique by the dentist. A study on 52 patients showed an average value of 0.3 mm for the transversal resiliency, which can be considered as physiological range. The results were discussed along with the question for the relevance of transversal TMJ-resiliency measuring regarding TMJ-disorders. PMID- 2220105 TI - [Gerontoprosthesis. Concept of rebuilding old complete dentures]. AB - If aged patients who have been wearing their full dentures without complications so far, need further prothetic treatment, the dentist must not replace the old denture by a completely new one. It is better to rebuild it step by step. This demand is based on the following theses: --Nobody but the patient himself is able to perform functional movements. --Unless bite and occlusion are correct, patients are not able to perform accurate functional movements. --When bite and occlusion have been checked and, if necessary, improved, bases and alveolar ridges must be congruent. PMID- 2220106 TI - [Injury-free removal of cemented crowns and bridges]. AB - Seven methods for removing crowns and bridges were studied in in vitro tests. Systems gripping the crowns on both sides led to the best results. Cemented crowns were loosened by ultrasound. All restorations could be removed after an average time of 6 1/2 min ultrasound influence. The increase of temperature in the pulp chamber requires sufficient waterspraying. PMID- 2220107 TI - [Polymerization shrinkage of denture resins in different preparation procedures]. AB - The Intention of this study was to examine and compare the effect of three different polymerization systems on the dimensional changes of denture-resin. The development of the fissure has been measured at five fixed points at the posterior border of upper complete dentures after a 4-weeks'-storage in water and saliva respectively. The perform-Inkovac-System showed the best, the SR-Ivocap System the most unfavorable results; the conventional "stuff-press-system" gave only medium satisfaction. PMID- 2220108 TI - [Is the German dental industry ready for the future?]. AB - The future perspectives of the German dental industry will depend on the individual productivity of the different manufacturers and especially on the political and economic development of Europe as a whole. National, European and international standarization will play an important role with work safety and environment protection as center points. Not innovations but the consolidation of product fabrication selection and use - with quality assurance as a common objective of the dental world - will be one of the major challenges in the near future. PMID- 2220109 TI - [Efficacy of different therapeutic procedures in treatment of inflamed primary tooth pulps. Results after 6 years]. AB - The efficiency of 3 different methods of primary pulp therapy (pulpotomy with formocresol in one and two appointments, pulpotomy with Triopaste) was studied over a period of 6 years in more than 300 teeth. The clinical results show a 98% success rate in the formocresol-treated teeth compared to only 55% of the Triopaste-group. PMID- 2220110 TI - [Comparative investigations of new dental electrosurgical instruments]. AB - 11 electrosurgical units of several manufactures were analysed by physical measurements. Conventional units and those with constant output voltage demonstrate nearly identical behavior in their voltage- and power-characteristics at load-impedance occurring during dental electrosurgery. So far there are no advantages of simple voltage control. We did not find technical deficiencies concerning security in the modern units examined. PMID- 2220111 TI - [Possibilities of crowning damaged primary teeth]. AB - Supply of extensively destroyed primary molars with preformed stainless steel crowns has been a method approved for decades and can be carried out in practice without taking a lot of time and financial costs. Maintenance and reconstruction of primary anterior teeth by ready made or individually manufactured crowns is necessary also for phonetic reasons. Depending on the grade of destruction of the clinical crown different possibilities for restoration are available: that is for the group of preformed types pedoformstripcrowns, polycarbonate crowns and stainless steel crowns with a composite facing, and for the group of individual manufactured crowns as resin crowns and short-pin crowns. PMID- 2220112 TI - [Considerations of precision and consistance of mandibular transverse hinge axis]. AB - This paper deals with the nature of mandibular hinge axis and the consequences for its application in diagnostics and treatment. The transversal hinge axis of the mandible can be characterized as an exact and true axis of pure mandibular rotation or a more or less exactly located axis as a result of a combined rotation and translation of the condyles. During opening movements of about 8 mm already an insignificant gliding of the condyles of 0.5 mm displaces the individual located hinge axis of more than 6 mm in its relation to the lower jaw. The true hinge axis as it is needed for achsiographic or pantographic registration techniques has inevitably not to be identical with the transferred axis for mounting casts in an adjustable articulator. PMID- 2220113 TI - [Nutritional care and guidance in caries active patients]. AB - Nutritional care and nutritional guidance are an important column of prophylaxis against dental caries and illness of the paradentium. Since these diseases, not neglibly resulting from influences of civilization, occur more and more frequently and on younger patients, suitable strategics for nutrition-anamnesis and nutrition-advice are required. Tooth-healthy nutrition must have the particular priority on already caries-active persons. The author tried to design a conception for the registration of caries-favourable influences, for recognizing special types of caries caused by nutrition and of individual instructions of nutrition. PMID- 2220114 TI - [Root fractures and tooth luxations. 1]. AB - Root fractures and subluxation of teeth often play only a minor role in the discussion of the therapy of traumatic tooth defects. This contribution discusses possible therapeutic approaches as well as prognosis and long-term results in cases of tooth root fractures and partially dislocated teeth. The primary aim of the therapy is to avoid further damage to the developing teeth of the first set, and to keep the permanent teeth in a proper condition for the maximum time possible. PMID- 2220115 TI - [Results of incorrectly positioned hinge axis on axiographic tracings of mandibular movement]. AB - This article deals with the different influences of an incorrectly located or arbitrary hinge axis upon axiographic tracings of mandibular movements. Unless the recorded curvatures of the three-dimensional pathways of the condyles start from true hinge axis points, paraxial distortions of the tracings will be the result. These recording errors can be so outstanding, that essential advantages of the modern electronical registration systems like the possibility of high resolution measurement will become uncertain. Within the scope of instrumental analysis of stomatognathic disturbances distorted tracings can lead to false diagnosis easily. PMID- 2220116 TI - [Possibilities of prosthetic rehabilitation of edentulous patients using cephalometric analysis]. AB - Cephalometric research showed an obvious and definite trend. Skeletal proportions and relations influence and determine the individual structure of the masticatory system. Transferring the relations to the edentulous patient the position and the inclination of the teeth and the occlusal plane can be determined. The evaluation of cephalometric analysis in edentulous is shown. The proceedings are demonstrated in two clinical cases. PMID- 2220118 TI - [Preparation and insertion of computer-designed ceramic inlays]. AB - The CEREC-system allows the production and insertion of ceramic inlays chairside in one visit. For this purpose an optical impression of the cavity is made, the inlay is designed on the computer screen and ground from a ceramic bloc. The inlay is bonded to the tooth using acid etch technique and a luting composite. Finally occlusal adjustment is performed. The technical prerequisites and the clinical procedure are presented and discussed in comparison to other tooth coloured inlay systems. PMID- 2220117 TI - [Intraligamentary anesthesia. Procedures using high pressure injection system (Ultraject)]. AB - The intraligamental anaesthesia via the periodontic sulcus is to be applied with high pressure. Therefore special syringes are needed. However the forced application may produce in some cases unwelcome effects as e.g. the breaking of the cartridge. This paper presents an intraligamental syringe with a device limiting maximum pressure. Working with this syringe proved comfortable in practice. PMID- 2220119 TI - [Influence of registration plate placement on axiographic tracings of mandibular movement in transverse plane mandible]. AB - In all achsiographic techniques a non perpendicular alignment and adjustment of the sagittal-vertical registration plates to the centric positioned hinge axis leads to an incorrect recording of mandibular movements. Among other things the dimension of the registration error decisively depends on the quality and quantity of the angle of hinge axis inclination. The achsiographies of 234 patients were analysed. In most cases incorrect measurements of the individual Bennett angle of only 1-2 degrees were found. These deviations are not relevant and have therefore not to be taken into account. On the other hand differences of the correct and incorrect recorded Bennett angle between 3 degrees and 8 degrees could be registrated in more than 25%. These errors have to be considered in diagnostics and treatment procedures. Correcting methods and techniques are described and discussed. PMID- 2220120 TI - [Accuracy of fit and margins of laboratory-finished SR-Isosit composite inlays]. AB - 30 inlays were produced exactly by manufactures instruction using the SR-Isosit composite. Before cementation the marginal gaps of the inlays extended to 280 microns occlusal resp. to 350 microns gingivoproximal. After insertion the thickness of the luting composite ranged from 40 to 400 microns occlusal resp. from 40 to 470 microns gingivoproximal. Dye penetration test indicated that only 43.7% of the inlays had a good marginal behaviour after storage in water over a six month period. Particularly remarkable was the insufficient junction between the luting composite and the highly polymerized inlay. PMID- 2220121 TI - [Thermal dimensional stability of dental registration wax]. AB - Three bite registration waxes were tested for their thermic dimensional behavior under several heating and cooling conditions. Aluwax showed the smallest changes in length. Difficulties of application are expected because of its low softening temperature. There were greater dimensional changes with Beauty Pink Hard-Wax, but Kerr No. 8-Wax showed the greatest changes. The cooling method had a small, the heating temperature, however, a strong influence on the thermic dimensional behavior. These are the recommendations for the clinical application of the tested waxes: The bite registration material should not be heated more than necessary for achieving a sufficiently plastic quality for the registration. It should be stored in ice water to be resistant enough to deformation during the model mounting. PMID- 2220122 TI - [Corrosion resistance and bond strength of dental alloys]. AB - Investigated Ni-alloys, which showed extensive solubility of Ni particles in corrosion bathes due to DIN 13927, also revealed pronounced lost of bond strength to ceramic veneers when immersed into corrosion bathes of equal constitution. Noble metal alloys with a gold concentration more than 50 percent, however, showed no such large lost of bond strength. Pd alloys showed a lost of bond strength which increased with their Ga concentration. Co alloys revealed a behavior similar to the Ni alloys but with no obvious correlation between solubility and lost of bond strength. PMID- 2220123 TI - [Experimental investigation of ceramic materials for bonded metal ceramic systems]. AB - Opaque porcelain materials used for the bonding layer in metal-ceramic restorations were analysed. The type of bond failure, produced by a bond/shear test was determined and the differences between metal/ceramic systems with conventional opaquers and metal/ceramic systems with special bonding agents are discussed. PMID- 2220124 TI - [Non-precious metal dental alloys in laboratory tests--critical judgement of results]. AB - An in vitro corrosion investigation of 15 dental NEM alloys respecting the solubility of Ni and Co and the surface destruction shows that results can be interpreted only in combination of visual and SEM investigations. With these results it is possible to make a selection for clinical application. The inverse voltammetry is a sensitive quantitative method for very small amounts of ions in solutions. PMID- 2220125 TI - [Cyclosporin A-induced gingival hyperplasias: cross-sectional study of young organ transplantation patients]. AB - In this study 137 patients (30 adolescence, 2-21 years, 107 adults, 22-68 years), which had been treated with Cyclosporine-A, between 17 to 2461 days after organ transplantation, were examinated by gingival status. The severity of gingival hyperplasia increases in both groups with mean transplantations period, independent of mean daily doses of CsA and Azathioprin and independent of mean plasma concentration. Adolescence and adults differ significantly, in relation of each severity group frequency. The adolescence group includes 66.7% of the cases with gingival enlargement of severity degree 3. In both groups increases the mean value of PGI-Index with the severity degree. PMID- 2220126 TI - [19th annual meeting of the Japanese Society of Neuropsychopharmacology. Fukuoka, 24-25 October 1990 1989. Abstracts]. PMID- 2220127 TI - Role of neostriatal and mesostriatal or mesolimbic dopaminergic fibres in Parkinson's disease with and without dementia: prospects, concepts and facts. PMID- 2220128 TI - [Digital autopsy archive using the personal computer]. AB - The development of a dissection register for Legal medicine well differentiated and considering special requirement of the subject was not achieved in history because of complexity of post mortem findings in many cases. Realizing that an all satisfying concept failed we looked for the possibility of using electronic data processing for rapid and flourish collection of autopsy results not requiring much time for the coroner. Based on personal computer software "dBase" a database program was developed easy to handle using different forms asking for characteristic circumstances of the case and essential post mortem findings. Short codes for locations and ascertainments were chosen to enable rapid selection of interesting statements as far as handling for statistical evaluations later on. Less then 10 minutes are needed for recording post mortem results in this way short time after autopsy. PMID- 2220129 TI - [Age-dependent morphologic findings of the thyroid in sudden infant death]. AB - Age (eight days to 12 months) and degree of colloid depletion or colloid content of the follicles (normal, partially depleted, depleted) were correlated on the basis of 176 thyroid investigations in cases of sudden infant death syndrome (SIDS). In the 176 SIDS cases, a resting thyroid gland with normal colloid content could only be found in 14%, whereas partially depleted follicles were found in 35% and depleted follicles in 51%. 60% of all cases showed a large degree of epithelial desquamation up to collapse of all follicles. A marked capillary hyperemia was found in 48%. 80% of the cases showed a normal colloid content in the first month of life, and colloidfree follicles should not be detected in any case. An increased incidence of thyroid activation was obtained in the total number of cases only from the second month of life. The histomorphological appearance of the thyroid gland thus corresponds to that of healthy infants only in the first month of life. The question as to why there is an evidently raised thyroid activity in the subsequent months of life in SIDS cases is discussed. PMID- 2220131 TI - [Injuries of the occipital condyles in fatal traffic accidents]. AB - Among 600 deaths of traffic accidents we found injuries of the occipital condyles in 10 cyclists, 12 car drivers and 3 pedestrians. In most cases the collision speed ranged from 70 to 100 km/h. In 18 cases of direct head impact the more severe injury was on the opposite side, in 4 cases of indirect side impact (whiplash injury) on the same side. Most types of fractures were 12 horizontal disconnections and 4 fractures of the inner edges. In 9 cases the condyle fractures were on one side, in 16 cases on both sides. PMID- 2220132 TI - Chronic cadmium intoxication caused by a dental prosthesis. AB - We present a case of chronic cadmium intoxication caused by a gold dental prosthesis. The first symptoms of the disease appeared 2 years after insertion and gradually intensified over the next 3 years. Analysis of blood and urine samples, as well as parts of the prosthesis, revealed an excessive concentration of cadmium. The prosthesis was removed and the concentration of cadmium gradually returned to normal, with an amelioration of symptoms. This case illustrates the importance of investigating the possibility of intoxication with a heavy metal when symptoms of chronic illness accompany the presence of a prosthesis. PMID- 2220130 TI - [Detection of morphine and codeine in blood samples with gas chromatography/mass spectrometry (NCI and PCI) for differentiating codeine use from use of heroin and morphine]. AB - Morphine and codeine were isolated from blood with C18 Bond Elut columns and derivatised with pentafluoropropionic anhydride (PFPA). The PFPA-derivatives were examined by means of gas chromatography/mass spectrometry using electron impact and chemical ionisation (positive and negative mode). The negative chemical ionisation, as most sensitive, was applied for the quantitation of both examined substances in forensic blood samples. PMID- 2220133 TI - [Sudden death in urticaria pigmentosa]. AB - A case of sudden death of a 25-year-old man, with a six years history of Urticaria pigmentosa, is reported. On a cold morning in November he was found lying dead on the lawn. Histology revealed no signs of systemic mastocytosis. The biochemical investigations (high free histamine level in urine) in addition to a BAC of 0,72 mg/g and the scene conditions (cold irritation) explained the mechanism of death, a systemic anaphylactoid reaction. PMID- 2220135 TI - [The 24th meeting of the German Rheumatology Society together with the 15th meeting of the German, Austrian and Swiss Societies for Pain Study. September 25 29, 1990, Hanover. Abstracts]. PMID- 2220134 TI - Fatal complications of intramuscular and intra-articular injections. AB - Four fatalities related to intramuscular and intra-articular injections are reported. In two of these cases a Staphylococcus aureus sepsis developed, as a consequence of injections into the left hip joint in one and in the lateral upper quadrant of the gluteal region in the other. The intra-articular injection of triamcinolone produced severe pain, but no marked signs of purulent arthritis were seen at autopsy, probably because of the anti-inflammatory effect of the corticosteroid. A cutaneous infection was seen in the gluteal region of the other patient, but no apparent abscess formation. In another case of intra-articular injection, purulent knee joint arthritis developed after an injection of glucosaminoglycan. The patient died of renal insufficiency, which was probably connected with the treatment of the arthritis with tobramycin and cefuroxim. The fourth case was that of a mentally ill patient who suffered sudden cardiac arrest after an intramuscular injection of chlorpromazine, but with no apparent signs of an anaphylactic reaction. It is suggested that vasodilatation and drop in blood pressure caused by the chlorpromazine could have had some effect, while cardiotoxicity of other psychotropic drugs with which he had been treated cannot be ruled out. PMID- 2220136 TI - [Pathophysiology and clinical significance of obstructive nephropathy]. AB - It is reported on the classification, pathophysiology and clinical relevance of obstructive nephropathy in the case of obstructive urinary transport disorders of the upper urinary tract. Despite successful experimental models a clinical indicator of reversibility of obstructive lesions may fail. PMID- 2220137 TI - [The value of diagnostic computerized tomography in tumor nephrectomy patients]. AB - In 84 patients after nephrectomy due to renal cell carcinoma a computerized tomography was performed to evaluate local tumor recurrence. The findings are classified stage-dependent. Other metastatic lesions were found by conventional radiologic methods. Based on stage-dependent different occurrence of metastases or local recurrences recommendations are made to the use of computerized tomography in the follow-up of patients suffering from renal cell carcinoma after nephrectomy. PMID- 2220138 TI - [Incidence of hemorrhage following suprapubic Cystofix puncture using a new trocar-cannula combination--a randomized, prospective comparative study]. AB - In this study a new trocar-cannula-unit(10 French) is introduced, which was used in a prospective randomised comparative study in 74 patients for suprapubic bladder punction. Another 75 patients served as controls receiving a suprapubic punction with the standard Cystofix (French 10)-system. In the control-group 9 cases (12%) of macrohematuria occurred. On the other hand we found that the incidence of macrohematuria was reduced to 5 cases (6.8%), when using the new trocar-cannula-unit, which had been developed in our hospitals. PMID- 2220139 TI - [Female hypospadias: a rare cloacal abnormality]. AB - The term "hypospadia feminis" means a congenital false urethral opening in the anterior vaginal wall proximal to the hymenal ring. In comparison to the male hypospadia it is a rare event. Obligatory an obstructive uropathy is found, but the pathophysiology remain obscure. PMID- 2220141 TI - [Evaluation of spermiogram findings using the revised WHO nomenclature]. PMID- 2220140 TI - [Urosepsis and uroseptic shock]. AB - The currently high letality rate of uroseptic shock may be reduced by early recognition of symptoms and adequate therapy with elimination of causes. Decisive for the septic shock are initial disturbances of the microcirculation in the presence of hyperdynamic circulatory regulation with following disorders of the coagulation system, tissue metabolism, acid-base-balance and heart contractility. In the therapeutic armament the important role of vasoactive substances is stressed. In an analysis of 59 patients suffering from urosepsis the intrinsic and iatrogenic causes, the bacterial spectrum and the emergency operative interventions are evaluated, whereas a letality rate of nearly 12% and an injury grade of 34% are estimated. PMID- 2220142 TI - [Status of office-EDP]. PMID- 2220144 TI - [Rotational dental instruments]. PMID- 2220143 TI - [Test of three unit adhesive bridges]. PMID- 2220145 TI - [Natural bone closure in complete lip, jaw and gum clefts]. PMID- 2220146 TI - [Handling problem patients in orthodontics]. PMID- 2220147 TI - [Prevention in Europe: Danes are in the forefront]. PMID- 2220148 TI - [Income projection for dentists is already decreased]. PMID- 2220149 TI - [EDP--documentation of dental examination in practice]. PMID- 2220150 TI - [Documentation of patient data in EDP forms]. PMID- 2220151 TI - [Amalgam concerns with removal]. PMID- 2220152 TI - [Electric sensitivity test with protective gloves]. PMID- 2220153 TI - [Artificial intelligence in dentistry]. PMID- 2220154 TI - [EDP--procedure data in a dental office]. PMID- 2220155 TI - [Market for dental computers. 10,000 computers in dental offices]. PMID- 2220156 TI - [Dental library seeks old dental catalogs]. PMID- 2220157 TI - [Alfred Kantorowicz and his student, Lem'i Belger]. PMID- 2220158 TI - [Caries prevention by the dentist--essential, efficient and rational]. PMID- 2220160 TI - [Prevention by fissure sealing: principles and practice procedures]. PMID- 2220159 TI - [Caries prevention by use of sugar substitutes]. PMID- 2220161 TI - [Basic principles and new concepts in prevention of marginal periodontopathies]. PMID- 2220162 TI - [Motivation for dental care]. PMID- 2220163 TI - [Active time management with help of two computers]. PMID- 2220165 TI - [The occurrence of Yersinia enterocolitica in sewage]. AB - Using a modified cold enrichment procedure Yersinia spp. were detected in 90.6% out of 32 raw waste water samples obtained within one year from two municipal sewage treatment plants. Moreover Yersinia were isolated from 50% of 6 effluent samples. Altogether 118 Yersinia strains were isolated and typed biochemically and serologically. 69 out of these isolates belonged to Yersinia enterocolitica, 60 strains to biotype 1, and 9 to biotype 4, serotype 0:3, 8 strains Yersinia enterocolitica serotype 0:3, biotype 4, considered to be a causative agent in human enteritis, harboured an 48 MD plasmid. The remaining isolates were identified as Yersinia frederiksenii (24 strains), Yersinia intermedia (22 strains) and Yersinia kristensenii (3 strains). The frequency of the isolation of Y. enterocolitica serotype 0:3, biotype 4 from sewage showed the same seasonal dependence as known from strains of human origin. In contrast to this, such dependence could not be found among other serovars of Y. enterocolitica and related species. PMID- 2220164 TI - [Pathohistology of inflammatory reaction on badly maintained periodontium]. PMID- 2220166 TI - Distribution, ecology, and immunosuppressive properties of Tricholoma populinum (Basidiomycetes). AB - Tricholoma populinum is widely distributed in Europe and North America. In the GDR 110 localities have been recorded, ranging from sea level to 470 m s.m. It is associated with many Populus spp. on acidic and neutral ground; its frequency has locally increased by recultivation of slap-dumps and waste land with poplars. Maximum of fructification is in the first decade of October. Investigations, stimulated by empiric observations on immunosuppressive effects of the mushroom in allergic diseases of man, lead to isolation of ergosterol peroxide as one substance responsible for these effects. PMID- 2220167 TI - [Minimal diagnostic program in urinary incontinence in the female]. PMID- 2220168 TI - [Effect of a new gestagen--dienogest--and its combination with ethinyl estradiol on the activity of biotransformation reactions]. AB - Caffeine is mainly metabolized by 3-methyl-cholanthrene-inducible cytochrome P 450, whereas metamizol (Analgin) is probably mainly metabolized by phenobarbital inducible cytochromes P-450. Therefore the elimination of caffeine from serum and the amount of the main metabolites of metamizol excreted into urine reflect the activity of these two cytochrome P-450 families. Sex hormones can influence the activity of cytochrome P-450. Dienogest is a new gestagen, used for temporary contraception. We investigated the effect of this new sexual hormone alone and in combination with ethynylestradiol on the elimination of both testdrugs. In 10 healthy volunteers dienogest 2 mg daily for 14 days have no effect on the metabolism of model drugs whereas the combination with 0.05 mg ethynylestradiol has an influence on the elimination of caffeine and metamizol. PMID- 2220169 TI - [Long-term analysis of causes, sites and results of treatment of urogenital fistulas at the Charite Gynecologic Clinic]. AB - Analyses of aetiology, localisation, and curing of urogenital fistulae permit conclusions as to efficiency of public health services. Recorded are 810 fistulae in 45 years which were analysed by 15-year periods. The ratio of obstetric to gynaecological fistula causes has remained unchanged through the entire period under review (10:90). However, substantial shifting was observed within either main group. In obstetrics, vesicocervical and vesicovaginal fistulae following caesarean section, have been predominant and on rising trend for 30 years. In gynaecology, vesicovaginal fistulae in the wake of vaginal and abdominal hysterectomy have considerably increased in the last 15 years. The present of benign to malignant primary diseases is 70 to 20%, as compared to 40:50% in the past. Vesicovaginal fistulae have continued to account for 60% of the general incidence. Urethral fistulae have gone up from 6 to 13%, while ureteral and trilocal fistulae have dropped from 20 to 16 and 11 to 7%. Fistula incidence figures at present are 0.01% obstetric as well as 0.2-0.5% benign and 0.7-1.4% malignant gynaecological causes. Rates of healing improved from 90 to 96% in obstetrics and stayed constant in gynaecology (94% benign and 80% malignant). The worst prognosis has continued to be recordable from trilocal fistulae. Current principles of therapy are, finally, put to discussion, together with modifications to the therapeutic regime. The conclusion is drawn that operations on women for urogenital fistulae should be performed only in urogynaecological centres and that fistula prophylaxis should be further intensified, especially in the context of gynaecological standard operations. PMID- 2220170 TI - [Local treatment of malignant pleural effusion in gynecologic tumors]. AB - Pleural effusions are a frequent complication of malignant gynecologic diseases, especially in breast cancer with an incidence of about 50%. Pleural effusions usually occur at a stage of the disease where no further curative therapeutic options exist. Therefore, the treatment should be effective and have a low side effect profile. The intrapleural administration of mitoxantrone in comparison with other pleurodesis techniques has been demonstrated to meet these requirements. PMID- 2220171 TI - [Pregnancy in diabetes insipidus--a case report with review of the literature]. AB - A 32 year old I P II G with preexisting diabetes insipidus was treated with 1-(3 mercaptopropionic acid)-8-d-arginine vasopressin (DDAVP) during pregnancy. An otherwise normal pregnancy was marked only with an excessive weight increase. A healthy girl was delivered by secondary cesarean section at term. Postoperative the mother developed a water intoxication accompanying oxytocin-infusion. During nursing the diabetes insipidus improved significantly whereby DDAVP doses could be reduced to 20-10 percent. We suppose an overreaction to endogene oxytocin with an antidiuretic effect. PMID- 2220173 TI - [When is cerclage indicated?]. PMID- 2220172 TI - [Endometriosis of the ureter]. AB - In this report two cases of hydronephrosis caused by an isolated ureter endometriosis are shown. The symptoms were few and not typical. The function of one kidney was severely diminished. PMID- 2220174 TI - [Echocardiography during pregnancy--longitudinal studies in primigravidae]. AB - As a result of hormonal changes processes of adaptation of the cardio-vascular system occur during pregnancy. These regulative changes are the basis for the present echo-cardiographic study which was made under standardized conditions with healthy primigravidae (n = 20) compared to nulligravidae (n = 24). Besides blood pressure and heart frequency dimension and volume sizes of the left ventricle (LV) as well as the LV-weight of muscle and the peripheral vascular resistance were analysed. As result significant increases from the 15th to the 35th week of pregnancy (SSW) could be found for the following parameters: heart frequency, arterial blood pressure, endosystolic volume of the left ventricle, cardiac output, left ventricular weight of muscle (p less than 0.01) endosystolic diameter of the left ventricle, enddiastolic volume of the left ventricle and heart index (p less than 0.05). The peripheral resistance was continuously decreased in the course of pregnancy (p less than 0.01). Compared to non-pregnant women the following parameters showed significantly higher values: heart frequency, cardiac output and heart index (p less than 0.01). The peripheral resistance was significantly lower in pregnant women compared to non-pregnant women (p less than 0.01). From the results the conclusion can be drawn that with statistic certainty echocardiography records adaptive processes of the circulation regulation relative to pregnancy and enables a separation in the groups of pregnant and non-pregnant women. PMID- 2220175 TI - [Contribution to cervical pregnancy]. AB - It is reported on a rare case of cervical pregnancy as a dangerous form of ectopic pregnancy. Etiology of this case is described only hypothetically like in literature. Clinical diagnosis always is difficult and was made seldom prior to operation. By ultrasonics cervical pregnancy diagnosis is possible if it is considered. On the other hand even that can mislead as cases from literature and our case show. For prognosis the same principles are applicable as with any other ectopic pregnancy--it must be finished definitely a certain number of pregnancies carried to term can be found in literature. Mortality has been reduced by the generally improved operation conditions. Primary hysterectomy has proven therapy of choice. Conserving uterus after ligature or embolisation of the internal iliac artery seems to be justified only in exceptional cases. In early pregnancy up to the 8th gestational week vacuum extraction or curettage can be tried. PMID- 2220176 TI - [Efficacy of an adjuvant norethisterone acetate therapy (NEA) of endometrial carcinoma treated with primary surgery or irradiation]. AB - The efficiency of NEA (norethisteronacetate) as an adjuvant hormone therapy in 196 pat. suffering from endometrial cancer has been evaluated in a prospective randomized trial. Primarily 93 patients had been operated on and 103 ones irradiated. From these 45 patients following surgery and 51 ones following radiation therapy had been treated with NEA. Schedule of adjuvant NEA therapy was for a time 6 ms 50 mg/d followed by 6 ms pause and so on till 5 years post op. 5 years survival in the operation group was 91.7 per cent without and 81.6 per cent with NEA, in the irradiated group 43.1 per cent and 44.8 per cent respectively. Side effect (47.9%) were caused by NEA at least twice higher than in control groups. IN CONCLUSION: the adjuvant hormone treatment without hormone receptor analysis is not recommendable. PMID- 2220180 TI - [Is radioisotope placental perfusion determination still acceptable today in the diagnosis of fetal retardation or placental insufficiency?]. PMID- 2220177 TI - [Hormone receptor status in adenomatous hyperplasia of the endometrium and endometrial carcinoma]. AB - 1. In glandular hyperplasia and endometrial carcinoma a correlation exists between the increased proliferation rate and the rise of the ER/PR-quotient. 2. The decline of both receptor concentrations and the increase of ER/PR-Quotient in the tumor and neighbouring, non-diseased tissue was demonstrated with increasing dedifferentiation, comparing endometrial carcinoma of different stages (G1 and G2, respectively). 3. In adenomatous hyperplasia the two receptors are significantly increased compared to normal cycling and glandular-hyperplastic endometrium, respectively; there the ER/PR-quotient is smaller than 1. After gestagen therapy decrease of both receptor concentrations demonstrates the success of therapy on one hand. On the other hand the higher decrease of PR shows, that duration and success of therapy could be limited temporally. 4. In endometrial carcinoma, especially in case of progression, recurrence and/or metastases, the determination of receptor status could be useful for therapy conception in the individual patient. PMID- 2220178 TI - [Image analysis study of squamous epithelial cells in cytological smears of the uterine cervix]. AB - The automated image analysis is a method, which may model essential effects of the cytologist's perception, combined with an increase of objectivity. We studied 9136 epithelial cells from 105 suspension smears of the cervix by means of image analysis. The results show that the process of maturation of squamous cells can be represented by image analysis parameters. Such a model enables an opposition of processes of differentiation and dedifferentiation. Furthermore subvisual changes in visual inconspicuous intermediate cells can be proved, too which appear in different degree correlated with the grade of dedifferentiation. At present a study is designed to investigate cases without any atypical cells, but having been classified as "positive cases" by the evaluation of intermediate cells in a long term follow-up. PMID- 2220179 TI - [Prenatal diagnosis of fetal small bowel stenosis. A case report]. AB - The authors describe an own case of fetal jejunal atresia with its antenatal ultrasound findings. With regard to the reported case the diagnostic and differential-diagnostic considerations of this rare fetal malformation are discussed. PMID- 2220181 TI - Phagocytosis of opsonized fluorescent microspheres by equine polymorphonuclear leukocytes. AB - Equine blood polymorphonuclear leukocytes (PMN) were isolated by buffy coat and hypotonic lysis of residual erythrocytes. A highly reproducible method is described for measuring the uptake of opsonized latex microspheres by equine PMN using flowcytometry. The use of cytochalasin D allowed for differentiation of ingested from attached particles. The kinetics of phagocytosis in vitro is shown for different experimental conditions. We developed an assay for evaluation of phagocytic capacity of PMN which allows the assessment of drugs for their influence on phagocytosis in vivo as well as in vitro. PMID- 2220182 TI - [Comparative studies of the paraspecific immunostimulation (paramunization) by bacterial lysates in bacterial infection models and in the cytotoxicity test]. AB - Bacterial lysates of different bacterial strains (E. coli, B. bronchiseptica, P. haemolytica) were prepared by heating, acid- and alkaline-hydrolysis. Lysates were tested for their immunostimulating effect in bacterial infection models and with chromium 51 test demonstrating spontaneous (natural) cytotoxicity. Lysate production was standardized by protein- and Lps-determination. The alkaline hydrolysis reduced toxicity of Lps and increased the content of soluble bacterial protein. Heating and acid-hydrolysis did not alter bacterial suspensions with respect to Lps-toxicity and protein-content. Mice infected with P. aeruginosa, P. multocida, E. coli and L. monocytogenes (5-10 LD50) had a significantly longer survival time after prophylactic immunostimulation with bacterial lysates than control animals. No protection was observed in immunostimulated mice infected with Erysipelothrix rhusiopathiae. In the Pseudomonas infection model, bacterial lysates prepared by alkaline-hydrolysis had a 10 times higher immunostimulating effect than lysates prepared by acid-hydrolysis or heating. Bacterial lysates stimulated spontaneous cytotoxicity of natural mouse peritoneal killer cells after intraperitoneal application. Whole bacterial lysates had a higher NK activity as their corresponding purified lipopolysaccharide portion. PMID- 2220183 TI - Scanning electron microscopic characterization of bovine coronavirus plaques in HRT cells. AB - The ecology of cytopathic expression of bovine coronavirus (BCV) in HRT-18 cells was analyzed within virus-induced plaques by scanning electron microscopy. Virus replication was cytocidal for many HRT-18 cells, a function enhanced in the presence of trypsin. A monolayer of cells remained that imparted a characteristic turbidity to the plaque. These structurally normal, lysis-resistant cells did not stain with fluorescent antibodies specific for BCV antigens, failed to adsorb virus particles or mouse erythrocytes in contrast to the susceptible cells. The survival of cells in the plaque interior reflects a non-productively infected population with evidence of viral persistence. PMID- 2220184 TI - [Experimental studies of in vitro cultivation of the cells of Kartner honeybees (Apis mellifera carnica Pollmann, 1879)]. AB - A synopsis about published methods and results on experiments to cultivate bee cells in vitro is given. Experimental investigations were performed with haemocytes of larvae of the L-5 stage using many different media and methods for the preparation of primary tissue culture. Monolayers could be prepared and a high rate of reproduction has been achieved, although subpassages could not be obtained. Haemocytes could be kept alive up to 27 days by using BML-TC/7A medium according to Gardiner and Stockdale, modified by Skatulla (pers. communic., 1987). Further experiments are necessary in order to study the suitability of bee cells to detect specific pathogens and toxic substances. PMID- 2220185 TI - [Electron microscopic studies of mucosal extirpates of rabbits after after in vitro contact with Pasteurella multocida subsp. multocida strains]. AB - In vitro experiments of adhesion and colonisation of mucosal surface fragments (nose, trachea) from freshly killed rabbits with four strains of Pasteurella multocida subsp. multocida with different types of capsule antigen (A, D, without capsule) showed the following results: Above all the capsule serovar A strain, producing a capsule of hyaluronic acid and fimbria, were able to adhere and to form microcolonies on the mucosal surface. Microvilli of epithelial cells and mucus producing cells were recognized as the place of adhesion. The formation of microcolonies occurred with a destruction of the kinocilia, which was caused by a bacteria free culture filtrate as well. PMID- 2220186 TI - Aujeszky's disease in a horse. AB - A horse with neurological signs and severe meningoencephalitis caused by Aujeszky's disease is described. The diagnosis was established by immunohistochemistry, DNA-in situ hybridization and serological tests. Aujeszky's disease virus antigen and Aujeszky's disease viral DNA were detected in neurons of the cerebrum. In the serum of the horse antibodies against Aujeszky's disease virus were detected in a virus neutralization test, in a blocking ELISA which specifically detects antibodies against the glycoprotein I (Ig) of the virus, in an indirect double sandwich ELISA and with colloidal gold immunoelectron microscopy which detects antibodies directed against the envelope and nucleocapsid of the virus. Intranasal infection of two points with a high dose of Aujeszky's disease virus caused very wild and transient signs. Although the experimental infection induced virus neutralizing antibodies, it failed to induce gI specific antibodies. PMID- 2220187 TI - [The detection of antibodies to the agent of malignant catarrhal fever in sheep and goat sera]. AB - An epidemiologic study was undertaken by means of the SNT on three sets of sheep sera and one set of goat sera to evaluate for the occurrence of antibodies against strain WC11. Out of 791 sera of a sheep breeding organisation 57 samples (7.2%) showed positive titers. The positive samples originated from 24 farms (36.4%) out of 66 farms under test. Out of 118 sheep sera sent in from different parts of Austria 35 (29.7%) showed positive titers. 73 sheep sera out of a farm where MCF had clinically occurred were also tested. 20 samples (27.4%) scored positive. Also 40 goat sera (20.3%) out of 197 samples showed positive titers. The results are in accordance with publications from other countries. Special reference is made to goats as possible carriers and transmitters of MCF. PMID- 2220188 TI - [The genesis of permanent growth of the beak wattle of a wattle-type pigeon]. AB - Variation in size of warts located on the beak of wattle-pigeons represents a dominant trait of this breed. Excessive growth to extraordinary size in two breeds (barbs and carriers), in addition to a large beak, can cause losses due to the inability of the parents to feed the offspring properly. In older birds, respiration is impeded and the field of vision is limited. This permanent growth in barbs and carriers could not be attributed neither to an infection with papovaviruses, nor to the overexpression of the retroviral c-src-protooncogen. This finding, in conjunction with the genetic analysis, underlines that this prominent trait is genetically determined. PMID- 2220189 TI - Trials with an enzyme-linked immunosorbent assay (ELISA) for the diagnosis of subclinical genital infections in rams caused by Histophilus ovis and Actinobacillus seminis. AB - The performance of an enzyme-linked immunosorbent assay (ELISA) was evaluated in the serological diagnosis of subclinical genital infection in 6 naturally infected ram flocks and 2 experimentally infected ram hoggets. The test employs lipopolysaccharide (LPS) antigen prepared by autoclaving from Actinobacillus seminis and Histophilus ovis. A total of 193 sheep (118 unmated virgin rams and 75 mature breeding rams) were examined clinically, serologically (by ELISA) and bacteriologically (semen bacteriology) at the same time. Serum samples from all animals were also tested by an ELISA employing LPS antigen prepared from Brucella ovis in the same way. Shedding of A. seminis and H. ovis did not show close correlation with serological positivity (Table 1), as only 9 (15.0%) out of the 60 A. seminis shedders were ELISA seropositive at the same time. As regards H. ovis only 10 (19.2%) out of the 52 H. ovis shedders were ELISA seropositive at the same time. The results indicate that, when used alone, the ELISA employing LPS antigen is unsuitable for diagnosing subclinical genital infection caused by H. ovis and A. seminis in rams. The authors discussed shortly the employing fields of this ELISA test in the diagnostic work. PMID- 2220190 TI - Milk whey induction of agglutination in ovine and bovine mastitis Staphylococcus aureus. AB - A total of 59 mastitis staphylococcic strains were tested for growth agglutination upon supplementation of growth media with ovine and bovine milk whey and mammary secretions from dry cows. Differences were observed when comparing bacterial species or origins (ovine vs. bovine) of bacteria and whey. All of the ovine and bovine S. aureus strains tested, but only 4 among 22 other ovine mastitis staphylococcic strains, showed growth agglutination in Todd Hewitt broth (THB) supplemented with greater than or equal to 30% (v/v) ovine milk whey. None of the strains agglutinated during growth in regular THB medium. Ovine whey had an agglutination induction capacity higher than bovine whey (P less than 0.005), concerning the number of responsive ovine and bovine S. aureus strains. There were no differences between whey samples from different ewes with regard to their capacity to induce agglutination. Ovine S. aureus strains were more responsive than bovine strains of this bacterial species, concerning the number of responsive strains (P less than 0.001) to bovine whey (greater than or equal to 30% in THB), the proportion of responsive strains at low (10%) ovine whey concentration (P less than 0.001), and the strength of reaction (precipitation timing and clump size). Secretions from dry cows systematically induced agglutination in all of the bovine and ovine S. aureus strains tested. PMID- 2220191 TI - Complement-dependence of polymorphonuclear yeast cell phagocytosis: a comparison between man and various domestic animals. AB - The complement-dependence of polymorphonuclear yeast cell phagocytosis of sheep, goat, cattle, horse, dog, pig and man is determined by comparing the opsonizing abilities of untreated sera with complement-inactivated autologous sera at a serum concentration of 2.5% and at different phagocytosis periods. The performed phagocytosis assays only detects incorporated particles and allows for the differentiation of granulocytes with different quantities of phagocytosed particles. In sheep, horse and man the addition of heat-inactivated serum reduces the phagocytosis index to less than -80% of the value obtained at untreated serum addition at a phagocytosis period of 60 min. The other species show a smaller reduction ranging from -66.9% (dog) to 41.4% (cattle). The evaluation of the distribution pattern of granulocytes incorporating a certain number of yeasts offers significant differences in the investigated species. PMID- 2220192 TI - The role of intestinal volatile fatty acids in the Salmonella shedding of pigs. AB - Factors affecting colonization of the intestinal tract by salmonellas were studied in two pig herds. In herd H 18% of the faecal samples taken from live pigs and 30% of the colon content samples collected at slaughter contained salmonellas. In contrast, the 50 faecal samples taken from pigs of herd L were negative and only 2% of the colon contents collected at the yielded salmonellas. An antibacterial effect inhibiting salmonella multiplication was demonstrable in vitro in colon contents from pigs of herd L. No such effect was found to exist in samples taken from pigs of herd H. The antibacterial effect is due to the non dissociated volatile fatty acid (VFA) molecules present in the colon content. As the degree of VFA dissociation depends on the pH of the environment, at lower pH values (pH 6.1 +/- 0.2) of the colon contents from herd L the ratio of non dissociated VFA molecules is higher and the resulting antibacterial effect is stronger than in samples from herd H (pH 7.1 +/- 0.3). PMID- 2220193 TI - Serological reactions of leptospirosis-positive (MAR and CFT) bovine sera in ELISA. AB - The collection of test sera for measuring ELISA results was composed of bovine sera with MAT titres of greater than or equal to 1:200 in the leptospirosis MAT and of greater than or equal to 1:5 in the CFT together with sera from a serologically negative and clinically non-suspicious cattle herd. To establish cut-off ODs, the geometric mean net-extinction of the negative serum collection plus 1, 2, and 3 standard deviations were calculated. By comparison of 3 different conjugates from rabbits, it was demonstrated that results from anti total bovine Ig were superior to anti-IgG and anti-IgM conjugates. Considerations regarding sensitivity and specificity led to the recommendation to use a test serum dilution of 1:160, to apply anti-total bovine Ig conjugates, and to establish the cut-off OD at the geometric mean net-extinction of negative sera plus 3 standard deviations. Under such conditions, agreement between leptospirosis MAT/CFT positivity on the one side and ELISA positivity on the other was reached in 74%. This recommendation is made for cross-sectional studies but not for examinations of clinically suspicious cattle herds. PMID- 2220194 TI - In vitro and in vivo glucose consumption in swine eperythrozoonosis. AB - One complication of swine eperythrozoonosis is the hypoglycemia that occurs during parasitemia. To determine the cause of the hypoglycemia, we studied glucose consumption in splenectomized pigs infected with Eperythrozoon suis. With the rapid rise of erythroparasites, the in vitro glucose consumption of parasited whole blood increased dramatically, and hypoglycemia developed. Because mature porcine erythrocytes are impermeable to glucose, the increased glucose consumption is most logically the result of E. suis metabolism. Iodoacetamide and sodium fluoride (which inhibit glycolysis), but not sodium cyanide (which prevents cellular respiration), and tetracycline (which is used to treat eperythrozoonosis) inhibited glucose consumption. In vivo glucose turnover studies before infection and during peak parasitemia indicated an increased glucose production by infected pigs during parasitemia. The results suggest that hypoglycemia occurs during swine eperythrozoonosis because the parasite uses glucose faster than the gluconeogenic pathways can provide it. PMID- 2220195 TI - Comparison of six different regimens for the control of atrophic rhinitis in swine. AB - Effectiveness of six different programs of atrophic rhinitis (AR) control was evaluated under field conditions. Efficacy of treatments was recognized on the basis of--comparative evaluation of the average daily gain (ADG), morphometric examination of turbinate bones and computer conchal morphometry (TPR). Usefulness of the evaluated regimes differed significantly. TPR appeared to be the most objective method for AR evaluation. Correlation between severity of turbinate atrophy and ADG was only partial. PMID- 2220196 TI - Isolation of Mycoplasma arthritidis from the joint fluid of boars. AB - During an outbreak of a disease in a swine insemination centre in Bavaria, Fed. Rep. of Germany, characterized by conjunctivitis, severe polyarthritis and infertility mycoplasmas have been isolated from the joint fluids of the three boars investigated. Two of the isolate could be typed as Mycoplasma (M.) arthritidis which causes arthritis in rats, mice and rabbits, the third as M. collis, a probably apathogenic rodent mycoplasma species. One of the two isolated M. arthritidis strains (strain D 263) was injected intravenously in rats and mice, which developed mild to severe polyarthritis or even died, depending on the numbers of organisms inoculated. Since the bacteriological and virological investigations of the joints of boars did not yield a causative agent, it is to suppose that M. arthritidis played the substantial role in the production of the disease of the boars. It is very likely that the boars caught the mycoplasmas from rodents infected with the isolated species. PMID- 2220197 TI - On the importance of bacterial L-forms in pigeons. AB - Following a definition of bacterial L-forms and a literature review on introduction and reversion of bacteria to and from L-forms, respectively, the results of a study comprising 587 samples (316 pigeons and 271 pigeon eggs) are reported. As a control 25 free living pigeons and 25 eggs of those pigeons were used, because antibiotic treatment of these could be excluded. From 79 samples (75 pigeons and 4 eggs) Salmonella typhimurium var. copenhagen (STMC) was isolated (none from the urban pigeons), of them 11 in the L-form from joints and organs and 3 from eggs. 325 of other bacterial isolates were found as L-forms (= approx. 40%). Out of 168 serum samples investigated, 33.9% showed antibodies against STMC. Corresponding antibodies could only be demonstrated in 73.4% of the pigeons with a STMC isolate. The occurrence of L-forms explains resistance to therapy and the failure of vaccines. The high frequency of L-forms is probably an indication of an inconsequential use of antibiotics in managing pigeon diseases. PMID- 2220198 TI - Influence of estradiol administration to lactating cows on bacterial growth in milk whey. AB - Bacterial growth (E. coli) in whey was studied by turbidometric technique during estradiol benzoate administration (0.02 mg/kg of body weight/day for 12-19 days) to 13 ovariectomized cows at three stages (early, mid and late) of the 1st- and 3rd-lactations. Whey samples from cows at early stage (60-90 days) of 1st lactation promote the growth of E. coli during the estradiol treatment. This included a significant increase in the maximum turbidity and a decrease in the generation time. Bacterial growth was inhibited in whey from cows at other stages of lactation during the hormone treatment. The degree of inhibition varied at different stages of lactation. No significant alterations in the ability of whey to support bacterial growth were observed in 3 ovariectomized cows treated with the drug vehicle (arachis oil) alone. Majority of the quarters included in the present study were bacteriologically negative throughout the study. PMID- 2220199 TI - Production of interleukin 2 and expression of interleukin 2 receptors by pony peripheral blood lymphocytes after stimulation with a soluble fraction of Trypanosoma evansi. AB - Pony peripheral blood lymphocytes (PBL) were stimulated with a soluble fraction of Trypanosoma (T.) evansi (SF). As determined by 3H-thymidine incorporation, the cells underwent a proliferative response and were able to: a) produce a factor having the biological activities of interleukin 2 (IL-2) since their supernatants could support the in vitro growth of pony PBL stimulated with concanavalin A (Con A-blasts); b) undergo a further proliferative response when incubated in short term cultures with SF, human recombinant IL-2 (hrIL-2), or both c) bind specifically radiolabelled hrIL-2 (125I-hrIL-2). The date described here indicate that a soluble fraction of T. evansi stimulated pony PBL which subsequently produced IL-2 and expressed IL-2 receptors (IL-2R). PMID- 2220200 TI - Measurement of endotoxic activity in feces of normal horses. AB - Two chromogenic Limulus amebocyte lysate systems were evaluated for the measurement of endotoxic activity in feces of normal horses. Fecal extracts had neither non-specific nor inhibitory effect on the test reaction, and the two systems with different specificity showed equivalent results. Endotoxic activities in feces of healthy horses averaged 5.7 +/- 2.8 microns/g wet weight. Correlation between the endotoxin levels and the fecal microbial flora could not be determined. PMID- 2220202 TI - [An analysis of the peripheral blood picture in the suslik and the white rat at different seasons of the year]. AB - New data are presented concerning seasonal changes in the peripheral blood of hibernating and non-hibernating rodents. In non-hibernating rats, seasonal changes in the blood are mainly phenotypical. Hibernating mammals are capable periodically to renew cellular composition of the blood during winter and summer hibernation. PMID- 2220203 TI - [The direct stimulating effect of arginine vasotocin on the functional activity of the interrenal gland in the frog Rana temporaria]. AB - Using radioimmunoassay it has been detected that both nonoperated and hypophysectomized, lacking endogenous ACTH, frogs injected one or three times with arginine vasotocin (5.10(-9) M/kg b. w.) show a statistically significant increase of plasma corticosterone level as compared with that in control animals and frogs injected with Ringer solution. The level of 11-hydroxycorticosteroids (fluorometric determination) in the interrenal gland decreases significantly only in animals three times injected with arginine vasotocin. It is assumed that arginine vasotocin produces a direct stimulatory effect on corticosteroid producing cells of the frog interrenal gland. PMID- 2220205 TI - [The late prolonged motor discharges during stimulation of the segmentary afferents in rat pups: the age-related characteristics]. AB - In experiments on intact 5-30-day rat puppies under slight urethane narcosis, stimulation of contralateral afferents evoked late prolonged discharges in extensor muscles. Apart from these discharges, studies were also made on the outbursts of autogenic periodic motor activity. The specific feature of late discharges within the first 10 days is their extreme duration and the presence of rhythmic components. With respect to the pattern and temporal parameters, there is a strong similarity between late discharges and autogenic periodic motor activity which is typical of newborn rats. The decrease in the intensity of late discharges in ontogenesis is paralleled by inhibition of autogenic activity. The data obtained indicate that late discharges are genetically related to the ancient property of the central nervous system, i.e. the capacity to self excitation and maintenance of active state. PMID- 2220204 TI - [The effect of dehydration on the functional activity of the interrenal gland in adenohypophysectomized Rana catesbeiana frogs. A preliminary report]. AB - A significant increase of the content of corticosterone in the blood collected from intravenous cannula or by intracardiac punction has been detected using radioimmunoassay in non-operated and adenohypophysectomized frogs Rana catesbeiana subjected to dehydration in 6.2% mannitol solution during 24 hours. The osmolality of the blood plasma of these animals also increases although less significantly than the growth of plasma corticosterone content. There is a tendency to substantial increase of plasma arginine-vasotocin level prior to the growth of corticosterone level, already after 6 hours of dehydration. Based on the present results and literature data, it is suggested that in adenohypophysectomized frogs lacking endogenous ACTH just the increase of blood arginine-vasotocin level results in a substantial activation of corticosteroid producing cells of the interrenal gland and in the growth of plasma content of corticosterone. PMID- 2220206 TI - [The late prolonged motor discharges during stimulation of the segmentary afferents in rat pups: the effect of L-DOPA]. AB - In experiments on 5-30-day rat puppies, under slight urethane narcosis, studies have been made on the late prolonged discharges in extensor muscles evoked by stimulation of contralateral tibial nerve before and after injection of DOPA. Within the first 16 days, the drug completely abolished or significantly reduced late discharges, increasing the spontaneous motor activity. Beginning from the 16th day, periods of potentiation of late discharges were observed. The data obtained are discussed in relation to the development of mechanisms of control of the activity of spinal generators which are responsible for late discharges and spontaneous motor activity. PMID- 2220207 TI - [The wakefulness-sleep cycle in rats with a genetic predisposition to catalepsy]. AB - Neurophysiological studies on wakefulness-sleep cycle have been made in rats selected for hereditary inclination to catalepsy. It was shown that in these animals, the stage of delta-sleep is significantly reduced, whereas the duration of a superficial slow-wave sleep is increased. In a sleeping phase of the cycle, large amount of spindles in the range of alpha- and beta 1-oscillations was observed, especially significant in electrograms of n. caudatum and sensorimotor cortex. This activity is considered as a pathological manifestation of a transient hypnotic phase which includes the increase in immobilization of a cataleptic type. PMID- 2220208 TI - [Differences in the corticofugal facilitating effect on evoked potentials in the neostriatum of rats and monkeys]. AB - Identical facilitation of the primary response to peripheral stimuli in rats and monkeys has been induced by local superficial cooling of the cortex in the somatosensory area S1. Higher facilitation of the evoked potentials was observed in the neostriatum of rats. Correlation of the evoked potentials with primary responses was more significant with respect to temporal than amplitude parameters. In monkeys, "cool" facilitation of the cortical primary response did not result in facilitation of the evoked potential in the neostriatum. Temporal correlation between the primary response and the evoked potential was less significant, whereas correlation in the amplitude was absent. The data obtained indicate the existence of differences in functional organization of corticofugal influences upon the neostriatum in rodents and primates. PMID- 2220209 TI - [The ontogenetic characteristics of the effect of stimulating the "reward zones" on the evoked potential in the parafascicular complex of the rabbit]. AB - In experiments on 24 anaesthetized 30-40-days rabbits, studies have been made of the effect of stimulation of the "reward zones" on the evoked potentials in the parafascicular complex in response to nociceptive stimulation of the hindlimb. It was shown that the effect of depression depends on the strength and duration of stimulation, being more evident in animals with a strong reaction to self stimulation. A comparison was made of analgetic effects produced by stimulation of the reward zones in various brain structures (the anterior, median and posterior lateral hypothalamus, the capsula interna, subthalamic region, etc.). Original description is presented of ontogenetic peculiarities of the recovery period for the evoked potentials after cessation of stimulation. The data obtained are discussed in relation to functional properties of nonspecific thalamic system of rabbits at the given stage of their development. PMID- 2220201 TI - [The presence of a correlation between erythrocyte acetylcholinesterase activity and body mass in small rodents]. AB - Studies have been made on the activity of erythrocyte acetylcholinesterase in 18 species of wild and laboratory rodents. Significant differences in the enzymic activity unrelated to taxonomic position of rodents were revealed. Negative correlation was found between the enzymic activity and body mass in rodents. The relationship between these parameters for wild rodents is approximated by an allometric equation Y = 1.1 . X-0.73, for laboratory species--Y = 1.5 . X-0.41. It is suggested that the revealed relationship indicates the existence of a connection between the activity of erythrocyte acetylcholinesterase and the intensity of metabolism in small rodents. PMID- 2220213 TI - [The status and outlook for mathematical modelling in epidemiology]. PMID- 2220212 TI - [The validation of the use of acarid antigens in developing vaccinal-serum preparations for the prevention of tick-borne encephalitis]. PMID- 2220211 TI - [Free amino acids in the blood plasma of lampreys, frogs and rats]. AB - Free amino acids in the blood plasma of lampreys, frogs and rats were determined by HPLC. In spite of quantitative differences in the total pool of free amino acids, the specific content of physiologically important amino acids is quite similar in representatives of different classes of vertebrates, from cyclostomes to mammals. PMID- 2220214 TI - [The article by Iu. P. Solodovnikov The etiological structure of bacterial dysentery in the USSR]. PMID- 2220210 TI - [The transventricular pathway of hypothalamic neurohormone distribution--the most ancient mechanism of neurohormonal regulation]. PMID- 2220215 TI - [The infection of monkeys with Ureaplasma urealyticum serovar VIII]. AB - The possibility of modeling chronic infection on monkeys by the injection of the culture of U. urealyticum, serotype VIII, was shown. The infection of monkeys with these microorganisms introduced in a single intraperitoneal injection resulted in the generalization of the process, which was manifested by the persistence and reproduction of the infective agent in the organs and blood of the animals for as long as 6 months (the term of observation). Lymphoid hyperplasia in the organs of immunogenesis and transitory immunomorphological reaction in the tissues of some organs of the urogenital system were noted. The localization of infective agents in some endocrine glands was not accompanied by disturbances in their function. PMID- 2220216 TI - [The use of a molecular hybridization method for studying the enterotoxigenic properties of Salmonella]. AB - The occurrence of the tox gene among 320 Salmonella strains of 23 serovars, differing in their origin, sensitivity to antibiotics, the presence of R-plasmids and a number of biochemical properties, has been studied by the method of DNA-DNA hybridization in situ. Essential differences in the occurrence of the tox gene have been detected both among S. typhimurium hospital strains and strains isolated in sporadic diseases, from the environment, from animals and among salmonellae belonging to different serovars. The direct correlation between the presence of the enterotoxigenicity gene and plasmids controlling resistance to antibiotics in Salmonella strains has been established. The expediency of using the method of gene probing for the study of the enterotoxigenic properties of salmonellae has been substantiated. PMID- 2220217 TI - [A radioimmunoprecipitation method in the serodiagnosis of HIV infection: the development of the optimal conditions for its performance and the evaluation of the possibilities for its use]. AB - The optimum conditions for using the method of radioimmunoprecipitation (RIP) for the detection of human immunodeficiency virus (HIV) in serum samples have been established. Out of several available cell lines persistently infected with HIV, specially selected line 17 has been chosen. The characteristic feature of this is the high and stable (under the conditions of prolonged cultivation) accumulation of virus-specific proteins in infected cells. The optimum conditions for making the test and its evaluation have also been established. The data of literature on the advantages of the method of RIP over such traditional methods as the enzyme immunoassay and immunoblotting have been confirmed. Thus, the presence of specific antibodies in several serum samples registered as false negative has been established. The intertypical reactivity of two serotypes of the virus, HIV 1 and HIV-2, has been studied. Cross reactivity of antibodies with respect to the HIV gene gag, but not with respect to viral glycoproteids, has been established. Ideas on the expediency and prospects of using RIP for the serological control of HIV infection are presented. PMID- 2220218 TI - [An analysis of the dysentery epidemic process in Blagoveshchensk]. AB - The retrospective analysis of dysentery morbidity in Blagoveshchensk for the period of 1960-1987 was made. The regularities linking general natural and biological factors triggering the epidemic process with dysentery morbidity among the population are emphasized. The study revealed that under the conditions of Blagoveshchensk dairy products were of major epidemic importance among factors contributing to the transmission of dysentery. Such a factor as flies also had a definite influence on the epidemic process of dysentery. Another risk factor was drinking water which influenced the epidemic process both directly and indirectly through dairy products and, probably, other foodstuffs. Reliable correlation between dysentery morbidity among the population and the quality of dairy products, tap water and the number of flies was established. PMID- 2220219 TI - [An outbreak of ornithosis at a textile factory]. AB - For the first time an outbreak of ornithosis at a textile factory is described. The data on the specific epidemiological features of the outbreak, the specific clinical features of the disease, the results of catamnestic observations and the study of the titers of specific antibodies in the complement fixation test are presented. PMID- 2220220 TI - [The use of pharmacological screening for characterizing the toxicity of pertussis vaccines]. AB - The influence of pertussis preparations, introduced by oral and parenteral routes, on the detoxifying function of the liver and the state of the nervous system of the animals was studied by methods used in pharmacology and toxicology. The use of these methods made it possible to find out side effects produced by corpuscular pertussis vaccine, introduced parenterally, on the detoxifying function of the liver and the state of the nervous system of the animals. The negative influence on the nervous system was more pronounced after the injection of the commercial adsorbed diphtheria-pertussis-tetanus vaccine used in this investigation than after the injection of pertussis monovaccine. The oral administration of corpuscular pertussis vaccine exerted no negative influence on the above-mentioned body functions of the animals. PMID- 2220221 TI - [The efficacy of a cultured rabies vaccine studied on guinea pigs previously infected with the rabies street virus]. AB - In this work materials on the development of an experimental model for the study of rabies vaccines are presented. The comparative study of different immunization schedules for vaccines with different protective potency has been carried out. Guinea pigs infected with street rabies virus, strain k, were used as an experimental model. As shown in this investigation the optimum method of infecting the animals with strain k was intramuscular injection causing 50% mortality among the animals, the incubation period lasting 10-24 days. Only those tissue-culture rabies vaccines which had activity equal to 1.0-1.3 I. U. and, when injected into the animals, ensured survival rate ranging from 57% to 76%, depending on the immunization schedule, were shown to possess protective potency. It should be pointed out that survival rate among the animals receiving the preparation according to the reduced schedules recommended by WHO was higher than among those immunized daily for 14 days. In all groups immune response was observed. Still in the animals receiving the preparation according to the reduced schedules a higher level of virus-neutralizing antibodies was registered. Thus, an experimental model capable of being used for the evaluation of the quality of existing and newly developed antirabies preparations was obtained. Besides, we believe it to be expedient to carry out the field trial of rabies vaccines with activity equal to 1.0-1.3 I. U., using the reduced immunization schedules. PMID- 2220225 TI - [A method for the experimental determination of the intensity of immunity from a series of different antigen doses]. AB - A new immunological regularity has been discovered mathematically; proceeding from this regularity, a simple index characterizing the immune responsiveness of animals has been proposed and a new (universal) method for the determination of the intensity of immunity has been developed and checked according to experimental data. PMID- 2220222 TI - [The functional characteristics of the peripheral blood granulocytes in erysipelatous inflammation]. AB - The receptors (FcR, C3R) and functional activity, determined by the nitroblue tetrazolium (NRT) test, of polymorphonuclear leukocytes (PML) of low and normal density were studied in erysipelas patients. The leukocytes were obtained by sedimentation on the 2-stage gradient of Ficoll-Verographin (1.077 and 1.119 g/cu cm). No statistically significant difference in the average group indices between "light" and "normal" PNL of erysipelas patients were detected. In comparison with donor PNL, higher expression of C3R, a high spontaneous NBT(+)-PNL level and poor response to stimulation with IgG in the NBT test were observed on granulocytes of the patients. The short-term treatment of the whole blood obtained from the patients with Streptococcus haemolyticus allergen led to a significant increase in the output of "light" PNL. As negative control, brucellin treatment was used, which produced no essential effect. The treatment of donor blood with the above mentioned antigens did not significantly affect the density of PNL. These facts suggest that in erysipelas the presence of "light" PNL is linked not with the release of granulocytes from the marrow, but with the activation of leukocytes by the products of infective inflammation. PMID- 2220224 TI - [Changes in the membrane lipids and lymphocyte function in staphylococcal infection and the development of delayed hypersensitivity]. AB - Experimental staphylococcal infection was reproduced in rats by the intraperitoneal injection of S. aureus strain 75. The degree of the development of delayed hypersensitivity (DH) to staphylococci, microviscosity, the levels of free radical oxidation and antioxidation resistance were evaluated in the dynamics of the infectious process by the methods of chemiluminometry and fluorescent probing with pyrene. The functional activity of lymphocytes was determined by the inclusion of 3H-thymidine into DNA as the consequence of stimulation with phytohemagglutinin. The development of DH was found to depend on the microviscosity and antioxidation resistance of membrane lipids. The increase of microviscosity and the simultaneous decrease of the induction time of chemifluorescent rapid flash inhibit the development of DH, leading to the aggravation of the infectious process. The increase of fluidity and the accumulation of antioxidants facilitate the development of DH and lead to a milder course of the infectious process. PMID- 2220223 TI - [Candidal carriage and the development of invasive candidiasis of the organs of the digestive tract during experimental immunodepression]. AB - After infecting healthy mice with Candida by their oral administration the fungi are rapidly eliminated from the digestive tract. In the animals, immunosuppressed by the injection of cyclophosphamide, the prolonged persistence of Candida in the digestive tract occurs, and the administration of Candida in considerable doses over prolonged periods in combination with the injections of high doses of immunosuppressing agents results in the development of profound invasive lesions, in some cases leading to the dissemination of the process. PMID- 2220226 TI - [The preparation of an IgG diagnostic agent based on stained polyacrolein latexes for use in the latex agglutination reaction]. AB - IgG diagnosticum for measuring the concentration of 131I-labeled IgG antibodies to enteric antigen beta 1MA by the latex agglutination inhibition (LAI) test has been prepared on the basis of polyacrolein latexes. A method for the titration of anti-IgG antibodies with the use of the above diagnosticum has been developed, based on the late, agglutination (LA) test. The optimum conditions for the microtitration variant of the LA and LAI tests have been defined. High sensitivity, specificity and simplicity of analysis with the use of latex IgG diagnosticum have been demonstrated. The newly developed methods have been successfully used in laboratory trials of a new diagnostic radiopharmaceuticals for the assay of 131I-labeled antibodies in this preparation and for the detection of side effects of immunization on the recipients. PMID- 2220228 TI - [The results of preclinical trials of the Soviet recombinant preparation of human interferon alpha-2 (reaferon)]. PMID- 2220227 TI - [The immunological properties of the main outer membrane protein of Legionella]. AB - The immunogenic properties of Legionella outer membrane main protein (OMMP) were studied by its effect on the proliferative activity of lymphocytes in guinea pigs. Preliminary immunization with OMMP activated only the specific and nonspecific proliferation of spleen cells. After infection with Legionella, secondary immune response developed in the spleen and lungs of previously immunized animals, in contrast to intact ones, and the nonspecific proliferative activity of lymphocytes in the spleen and lungs of previously immunized animals considerably increased. These results are indicative of the fact that Legionella OMMP, similarly to other Legionella antigens and immunomodulators, may be used for the formation of protective immunity. PMID- 2220230 TI - [Pathophysiology of open fractures and principles of their treatment. Review]. AB - Authors have worked out in detail the problems of fractures associated with the injury of soft tissues. They use their own classification dividing these fractures into two major groups, and namely open and closed fractures. In each group they distinguish 4 degrees of severity of the injury of soft tissues. Of decisive importance for both the final result and the course of the treatment is the method of treatment which starts already on the scene of the injury. The whole therapeutical management up to the actual operation has several successive phases. The way of osteosynthesis can be decided upon only after the primary treatment of the wound which makes it possible to evaluate properly the condition of soft tissues and the contamination of the wound. Of vital importance is the radicalism of the primary treatment and the removal of all necrotic tissues. Potential defects can be temporarily covered with artificial skin and permanently with skin grafts or muscular, myocutaneous or fasciocutaneous flaps. PMID- 2220231 TI - [Long-term results of Ludloff's repositioning method]. AB - Authors have evaluated results of the surgical treatment of congenital dysplasia of the hip joint performed at I Orthopaedic Clinic in Prague in the years 1970 1985. In the course of this period open reduction according to Ludloff was performed in seventy children out of which eight times bilaterally. Fifty-six out of the total number of seventy children same for the follow-up check. The age of the children operated on ranged between five and 23 months; in six cases the operation was performed on both hip joints. The follow-up ranged from three to eighteen years with an average of eleven years. In all children the postoperative treatment consisted in the application of the Hanausek biomechanical apparatus. On the basis of clinical and roentgenological criteria the results were divided into fair and poor results. For fair result were considered the hips with a good range of motion (none of the motions was reduced more than by 50 percent of the normal range), patients did not feel any pain, the limb shortening did not exceed 1 cm and the Trendellenburg test was negative. From the roentegonological viewpoint for fair were considered the findings without persisting subluxation and dislocation with the spheric head (the asphercity on the Moose template did not exceed 2 mm) and without evident shape deformities of the proximal end of the femur (coxa vara, overgrowth of the greater trochanter). Only such hips which meeted both the clinical and roentgenological criteria were evaluated in general as fair, the other were assessed as poor. On the basis of these criteria the result of the treatment was evaluated as fair in 76 percent and poor in 24 percent of cases. The authors also observed the incidence of aseptic necrosis of the femoral head from the viewpoint of the types defined by Bucholz and Ogden. Necrosis of Type I was not found in the group, necrosis of Type II occurred 12 times, necrosis of Type III and Type IV three times each. No evident connection was found out between the incidence of the necrosis of head and the ligation of both branches of a. circumflexa femoris medialis. The main cause of the impossibility to perform reduction was the isthmus of the joint capsula in its inferomedial portion in the area of iliofemoral ligament. Of decisive importance for the development of the joint after open reduction was a perfect reduction of the head into acetabulum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2220229 TI - [The status of infectious and parasitic morbidity and the priority tasks in its decrease]. PMID- 2220233 TI - [Resection of the subtalar joint--long-term results]. AB - In the years 1965-1985 212 patients were treated at the I. Orthopaedic Clinic in Brno by means of the resection sub talo. 100 patients with 105 operations were checked up on average 13 years after operation. The average age in the time of operation was 27. Indicated for operation were in 54 cases patients with neurologic deformity of the foot, in 51 cases patients with a local deformity. Reported were 65 good, 25 fair and 15 poor results. Residual deformity occurred in 12 patients and severe instability of the leg also in 12 cases. Eight patients suffered from moderate arthrosis of the joint ankle, three patients had severe arthrosis. Pseudoarthrosis in the area of resection was found in 5 cases. Prior to operation it is inevitable to examine the stability of the talus and anterior subluxation of the ankle joint. In cases of the instability of the talus ankle arthrodesis is indicated. The authors put emphasis on the release of soft tissues prior to or during the operation. The work proves longterm usefulness of the resection sub talo. PMID- 2220232 TI - [Results of surgical treatment of dislocation fractures of the ankle joint]. AB - The authors have made evaluation of the surgical treatment of luxation fractures of the ankle in the period 1979-1987 in 105 patients (60 female, 45 male patients) in the age range from seventeen to eighty-one years, with the most frequent representation of the age group ranging from thirty-five to forty-five years. The group comprised 2,70 percent of fractures of type Weber A, 31.53 percent of fractures of type Weber B and 65.77 percent of fractures of type Weber C. 53 percent of patients were operated on the day of injury, 24.8 percent of patients were transferred with a delay from other clinics and in the rest of the patients the timely operation was contraindicated because of the poor local or general condition. The results were processed according to a uniform worksheet by the computer. On the basis of the evaluation there were found out 87.62 percent of successful and 12.38 percent of poor results. 93.3 percent of patients resumed their original jobs and there was no patient eligible for a full disability pension. The main cause of failure was the osteoarthritis of the ankle joint found out in connection with the inaffestable factors (such as defects of cartilage, nature of the bone lesion, luxation of talus, age and sex of the patient) and affectable factors (infection, failure of osteosynthesis, pseudoarthrosis of medial malleolus, non-anatomical position in the area of tibiofibular syndesmosis). The incidence of these negative factors may be reduced by a timely operation, precise surgical strategy and technique and proper post operative treatment. PMID- 2220234 TI - [Osteomalacia. I. Review]. AB - The authors present the survey of the history, diagnostics and treatment of osteomalacia with special treatment to Looser zone and Milkman syndrome. For the application in the clinical practice we recommend the bone index after McKenn. The authors point out favourable results of longterm vitamin D therapy. PMID- 2220238 TI - [Medical study in North America]. PMID- 2220237 TI - [The formal aspect of scientific research]. PMID- 2220235 TI - [Osteomalacia. II. The Milkman-Looser syndrome. Case report]. AB - The authors present the case study of Milkman-Looser syndrome in a 83 years old female patient. The diagnosis was made on the basis of typical laboratory and X ray findings. The authors point out excellent curative effect of vitamin D. PMID- 2220236 TI - [Chondrodysplasia punctata]. AB - Authors deal with the classification of chondrodysplasia punctata, in detail they analyze the clinical and radiomorphological symptoms. From the diagnostic viewpoint it is important to evaluate typical X-ray epiphyseal changes in the first year of age of the affected child. Clinical symptoms vary and they are not typical only for this disease. They are often combined with various congenital developmental anomalies. The case study presents the correlation between X-ray epiphyseal changes in the knee and the arthroscopic findings. PMID- 2220239 TI - Leopold G. Koss, M.D., F.I.A.C., 70th birthday. PMID- 2220243 TI - Peritoneal washing cytology in cervical carcinoma. Analysis of 109 patients. AB - The peritoneal washing cytologies of 109 patients (112 procedures) undergoing laparotomy for cervical carcinoma were evaluated retrospectively and compared with the clinical and pathologic findings. Nine patients (8.3%) had malignant peritoneal washings (including three of four with washings initially termed "inconclusive"). Four (4.9%) of the 82 patients with squamous carcinoma and 3 (16.7%) of 18 with adenocarcinoma had positive washings. Five (5.6%) of 90 washings obtained at initial explorations were positive, as compared with 4 (18.2%) of 22 washings obtained as follow-up operations in recurrent cases. The 111 peritoneal washing cytologies with a corresponding histologic evaluation of the peritoneal cavity showed a good correlation; peritoneal washing cytology had an efficiency of 91.0%, a sensitivity of 52.9% and a specificity of 100%. Two cases in which the cytologies were considered positive only after review had negative peritoneal histologies; both patients died of progressive disease within 11 months. Peritoneal washing cytology was positive in 5 (5.9%) of 84 cases with FIGO stage 1 cancers, 2 (18.2%) of 11 cases with stage 2 cancers, 1 (33.3%) of 3 cases with stage 3 cancers, and 1 (10%) of 10 cases with recurrent tumors. Eight (88.9%) of nine patients with malignant peritoneal washings died of disease from 3 to 15 months following surgery; one showed no evidence of disease at 9 months. These results suggest that: (1) cervical carcinomas are infrequently associated with a positive peritoneal washing; (2) peritoneal washing cytology is more likely to be positive in cases of adenocarcinoma than in cases of squamous carcinoma; (3) peritoneal washings obtained at the time of surgery for recurrence are more likely to contain malignant cells than are washings obtained during initial exploration; (4) nonkeratinizing malignant squamous cells may be confused with reactive mesothelial cells; and (5) peritoneal washing cytology is a relatively insensitive technique for detecting advanced cervical disease, but correlates with a poor prognosis when positive. PMID- 2220240 TI - Colonic cytology. A retrospective study with histopathologic correlation. AB - Three hundred sixty cytologic specimens obtained by colonoscopic brushing from 336 patients were compared with biopsy specimens simultaneously obtained for histologic examination. Of the cytologic specimens, 160 (44%) were positive for malignant cells, 37 (10%) contained suspicious cells, 54 (15%) had atypical glandular cells, 107 were cytologically negative, and 2 were considered unsatisfactory. Eight-four percent of the patients with cytologically positive smears and 54% of those with suspicious smears had malignant neoplasms in the simultaneously obtained tissue biopsies. Of the patients with follow-up, all with cytologically positive findings and nine with suspicious findings on the initial cytologic examination and simultaneous negative tissue biopsies, were subsequently found to have carcinoma of the colon. Cytology proved to have a sensitivity of 0.73 and a specificity of 1.00 while tissue biopsy showed a sensitivity of 0.81 and a specificity of 1.00. By combining the two methods, the sensitivity increased to 0.92. It is concluded that cytologic examination of colonic brushings is a highly accurate and reliable technique for the detection of malignant neoplasms of the colon and can preempt the use of biopsy forceps. PMID- 2220241 TI - Exfoliative colonic cytology. A simplified method of collection and initial results. AB - Exfoliative colonic cytology for the diagnosis of colorectal cancer has been largely abandoned due to (1) the widespread use of colonoscopy, (2) the cumbersome methods of cell collection and (3) the occasional difficulty of interpreting the cytologic findings in the presence of inflammatory bowel disease or adenomas. This paper describes a newly formulated bowel preparation for routine colonoscopy, based on imbibing 2 L to 4 L of a balanced electrolyte solution, in which the recovered precolonoscopic effluent (using a convenient disposable collecting kit) yielded cells for cytologic evaluation from 70% of a group of 80 patients at high risk for large bowel neoplasia. Cytology demonstrated neoplastic cells in most cases of endoscopically proven cancer. These results suggest that colonic exfoliative cytology may be useful as a supplemental test to routine colonoscopy. This could be enhanced by further methodologic modifications to the collecting and cytologic methods; large long term studies are needed to evaluate the potential usefulness of colonic exfoliative cytology. PMID- 2220245 TI - Fine needle aspiration cytology of squamous cell carcinoma of the breast. AB - A rare case of pure squamous cell carcinoma of the breast is reported in which the diagnosis was initially suggested by fine needle aspiration cytology. Smears and cell blocks of the aspirate showed atypical keratinized cells admixed with inflammatory cells. The diagnosis was confirmed by open biopsy. The excised tumor tissue was positive for both estrogen and progesterone receptors; flow cytometry showed a diploid DNA content and a high S-phase fraction. PMID- 2220242 TI - Fine needle aspiration cytology of pancreatoblastoma with immunocytochemical and ultrastructural studies. AB - The cytologic features of a pancreatoblastoma (infantile adenocarcinoma), a rare pancreatic neoplasm of childhood, are described. Fine needle aspiration (FNA) under ultrasound guidance produced a hypercellular specimen consisting of numerous oval-to-cuboidal cells that had a moderate amount of granular cytoplasm. Spindle-shaped, elongated and triangular-shaped epithelial cells were also seen, along with smaller cells that had a higher nuclear/cytoplasmic ratio and a denser cytoplasm. In addition, there were abundant fragments of stroma present, including some surrounded by epithelial cells. Immunoperoxidase studies performed on the aspirated material revealed positive staining of the epithelial cells for cytokeratin (AE1/3), including high and low molecular weight cytokeratin, carcinoembryonic antigen, neuron-specific enolase and alpha-1-antitrypsin. Ultrastructural examination demonstrated epithelial cells containing either large electron-dense zymogen granules in the range of 400 nm to 600 nm or small dense neuroendocrine granules measuring from 100 nm to 200 nm. This finding, in concert with the immunocytochemical studies, supported a "blastemal" cell origin with bidirectional differentiation for this unusual pancreatic neoplasm and enabled a specific preoperative diagnosis of pancreatoblastoma to be made. The differential diagnosis of pancreatoblastoma from other pediatric neoplasms involving the pancreas, including neuroendocrine tumors and neoplasms of acinar cell derivation, is presented. We believe that the FNA cytologic findings can lead to a correct diagnosis of pancreatoblastoma, especially when coupled with immunocytochemical and ultrastructural studies performed on the aspirated material. PMID- 2220244 TI - Density distribution, cytomorphologic features and immunologic characteristics of ovarian and endometrial clear cell carcinomas. AB - Three subpopulations of cancer cells with different morphologic features were separated by density gradient centrifugation of two ascitic fluids and one cystic fluid from one patient with ovarian clear cell carcinoma and one with endometrial clear cell carcinoma. Immunophenotypic analyses of isolated fractions using polyclonal and monoclonal antibodies against ovarian carcinoma-associated antigens revealed significant immunologic heterogeneity among the tumor cells. The identical histopathologic structures of the ovarian and endometrial clear cell carcinomas and the similar distribution and immunologic reactivity of the cell types isolated from the ascitic and cystic fluids confirmed the common histogenesis of both cancers. These findings suggest that the conventional cytologic diagnosis of clear cell carcinomas could be supplemented by immunofluorescent staining. Density gradient centrifugation appeared to be a useful method for the separation of mesothelial cells. PMID- 2220246 TI - Recurrent Hodgkin's disease in the breast. Diagnosis of a case by fine needle aspiration and immunocytochemistry. AB - Recurrent Hodgkin's disease involving the breast in a 17-year-old girl was diagnosed by fine needle aspiration (FNA) biopsy of a solitary mass that developed one year after "curative" radiation. Benign breast disease and breast carcinoma were ruled out upon cytologic examination of the FNA smears, which contained diagnostic Reed-Sternberg cells and the characteristic polymorphic background elements. Follow-up immunoperoxidase staining for Leu-M1 on destained smears confirmed the diagnosis. Definitive therapeutic measures were initiated after the FNA diagnosis. PMID- 2220247 TI - Fine needle aspiration biopsy of the breast. Influence of the number of passes and the sample size on the diagnostic yield. AB - The sensitivity of fine needle aspiration (FNA) biopsy of the breast as a function of the number of aspirations performed on any given lesion was investigated. Four separate aspirations each were performed on over 400 lesions of the breast, 93 of which yielded a cytologic diagnosis. The incremental diagnostic yields of each subsequent aspiration were tabulated. The first aspirate of the sequence gave the greatest yield, with smaller incremental yields on the second through the fourth aspirates. Benign and malignant lesions gave similar results, as did palpable and nonpalpable lesions (the latter being usually smaller in size). A mathematical extrapolation of the data indicates that three or four aspirations of any given lesion provide the optimal yield within the limits of practicality. This performance of multiple FNA biopsies is particularly important when the pathologist does not perform the biopsy, or is unable to assist in the immediate interpretation of the specimen to assess its adequacy. PMID- 2220250 TI - Suction sampling technique for obtaining standardized cytologic specimens from the oral mucosa. AB - To enhance the value of exfoliative cytology for the study of the oral mucosa, a simple apparatus was developed to permit adequate sampling of a specific site so that samples collected on different occasions could be compared. The device essentially consists of a collecting cup connected to a blood collection evacuation system. The collecting cup is a modified female half of a stainless steel filter holder supporting a 13-mm-diameter cellulose filter of 0.05-microns pore size. Suction pressure is applied by means of a 10-mL glass tube of premeasured vacuum. After positioning the collecting cup on the selected site on the buccal mucosa, the vacuum (440 mm Hg) is applied for five seconds. The mucosa is drawn in against the filter, producing a monolayered imprint of cells. This sample may be disengaged from the filter by agitation into a solution; this allows quantitative cytologic studies, such as the measurement of cell numbers by an electronic counter or the estimation of the areas of cells and nuclei by computer-aided image analysis of Cytospin preparations. Five separate samplings from each of three test subjects produced a harvest of 3,000 to 7,000 epithelial cells per sample; the cellular areas ranged from 784 to 1,052 sq microns while the nuclear areas ranged from 18.4 to 21.8 sq microns. PMID- 2220248 TI - Fine needle aspiration cytology of bone lesions. Analysis of a three-year experience in rural Africa. AB - FNA biopsies were performed on 24 patients with bone lesions. Cytology diagnosed ten of the cases as classic Burkitt's lymphomas. The cytodiagnoses in the remaining 14 cases were primary bone tumors (5 cases), bone cysts (2 cases), inflammatory lesions (4 cases) and inadequate material (3 cases). Smears of the Burkitt's lymphomas of the jaw contained starry sky macrophages and neoplastic lymphoid cells with deep basophilic cytoplasms and fine vacuolizations. Taking into consideration the load of Burkitt's lymphoma cases in Africa, FNA cytology appears to be a very simple method for getting a quick tissue diagnosis (results were available within 24 hours). For doctors working in tropical hospitals with limited facilities, FNA cytopathology is very useful for distinguishing between tumors and inflammations and for differentiating between benign and malignant tumors. PMID- 2220249 TI - Inflammatory pseudotumor of the lung diagnosed as granulomatous lesion by preoperative brushing cytology. A case report. AB - The clinical and cytologic features of a case of inflammatory pseudotumor of the lung are presented. Chest roentgenograms revealed a solitary circumscribed round mass in a nine-year-old boy. The mass was diagnosed as a granulomatous lesion by bronchoscopic brushing cytology. Although smears and cultures of sputum and brushing specimens were negative for tuberculosis, a tuberculin reaction was positive and antitubercular therapy was instituted. Since the mass had grown further after six months of therapy, an open lung biopsy was performed to resect the lesion and establish the diagnosis. Imprint smears of the cut surface of the lesion showed cytologic features similar to those of the brushings: short, spindle-shaped cells with a tendency to be arranged in stori-form patterns against a background of minimal necrotic debris. Histopathology established the final diagnosis of inflammatory pseudotumor, a rare granulomatous lesion radiologically resembling a true tumor. Since this lesion usually occurs in younger patients, inflammatory pseudotumor should be considered in pediatric cases with an intrapulmonary lesion that shows histiocytic spindle-shaped cells in stori-form patterns, but whose smears and cultures test negative for tuberculosis. PMID- 2220251 TI - 38th annual scientific meeting of the American Society of Cytology. Washington, D.C., November 7-11, 1990. Abstracts. PMID- 2220253 TI - Cytologic findings in spermatic granuloma. PMID- 2220254 TI - Megakaryocytes in a fine needle aspirate of the thyroid gland. PMID- 2220252 TI - Detached ciliary tufts in the aspirates of spermatoceles. PMID- 2220256 TI - The molecular and cellular biology of platelet-derived growth factor. PMID- 2220255 TI - Fine needle aspiration biopsy in the diagnosis of liver echinococcosis. PMID- 2220260 TI - Renal tubular reabsorption of calcium and sodium in primary hyperparathyroidism. AB - Nine patients with primary hyperparathyroidism were studied to investigate the renal tubular reabsorption of calcium and sodium. Fasting serum and urine samples were analysed, and the glomerular filtration rate and the renal plasma clearance of lithium were determined simultaneously. Comparison was made with 9 age- and sex-matched normocalcemic controls. In the proximal tubule, there was a significantly higher absolute reabsorption of calcium in patients than in controls, whereas the fractional reabsorption rate of calcium did not differ between the two groups. In the distal tubule, the absolute calcium reabsorption rate was significantly higher in the patients, whereas the fractional reabsorption rate of calcium was significantly lower than in controls. In the patient group there was a significantly positive linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption rate, but not between the increased capacity and the absolute distal calcium reabsorption rate. No significant differences were found in the renal tubular handling of sodium between patients and controls. Our results suggest that the increased capacity for tubular calcium reabsorption in primary hyperparathyroidism mainly is localized in the proximal tubule, and that the renal tubular handling of calcium and sodium in this disease differs from that in familial hypocalciuric hypercalcemia. PMID- 2220258 TI - Pyridostigmine partially restores the GH responsiveness to GHRH in normal aging. AB - In 11 elderly normal subjects and in 17 young healthy subjects we studied the response of plasma growth hormone to GH-releasing hormone (GHRH(29), 1 microgram/kg iv) alone and preceded by pyridostigmine (120 mg orally 60 min before GHRH), a cholinesterase inhibitor likely able to suppress somatostatin release. The GH response to pyridostigmine alone was also examined. Basal plasma GH levels were similar in elderly and young subjects. In the elderly, GHRH induced a GH rise (AUC, median and range: 207.5, 43.5-444.0 micrograms.l-1.h-1) which was lower (p = 0.006) than that observed in young subjects (548.0, 112.5 2313.5 micrograms.l-1.h-1). The pyridostigmine-induced GH rise in the elderly was similar to that in young subjects (300.5, 163.0-470.0 vs 265.0, 33.0-514.5 micrograms.l-1.h-1). Pyridostigmine potentiated the GH responsiveness to GHRH in both elderly (437.5, 152.0-1815.5 micrograms.l-1.h-1; p = 0.01 vs GHRH alone) and young subjects (2140.0, 681.5-4429.5 micrograms.l-1.h-1; p = 0.0001 vs GHRH alone). However, the GH response to pyridostigmine + GHRH was significantly lower (p = 0.0001) in elderly than in young subjects. In conclusion, the cholinergic enhancement by pyridostigmine is able to potentiate the blunted GH response to GHRH in elderly subjects, inducing a GH increase similar to that observed after GHRH alone in young adults. This finding suggests that an alteration of somatostatinergic tone could be involved in the reduced GH secretion in normal aging. However, a decreased GH response to combined administration of pyridostigmine and GHRH in elderly subjects suggests that other abnormalities may coexist, leading to the secretory hypoactivity of somatotropes. PMID- 2220257 TI - Thyroid hormones and thermogenesis: a microcalorimetric study of overall cell metabolism in lymphocytes from patients with different degrees of thyroid dysfunction. AB - We used microcalorimetry to measure lymphocyte heat production rate in patients with clinical and laboratory hyperthyroidism (serum TSH decreases, serum FT4 increases, serum FT3 increases), subclinical hyperthyroidism (serum TSH decreases, serum FT1 increases, serum FT3 =), and subclinical hypothyroidism (serum TSH increases, serum FT4 decreases, serum FT3 =) compared with healthy controls (N = 13). The lymphocyte heat production rate was significantly correlated to the free thyroxine level (r = 0.53, p less than 0.01) and to the free triiodothyronine level (r = 0.51, p less than 0.01) when calculated from pooled data for the three patients groups. The hyperthyroid patients (N = 8) had a significantly increased lymphocyte heat production rate, 3.43 +/- 0.25 pW/cell, as compared with 2.31 +/- 0.12 pW/cell in the control group (p less than 0.001). The groups with subclinical hyperthyroidism (N = 7) and subclinical hypothyroidism (N = 9) had lymphocyte heat production rates of 2.14 +/- 0.11 and 2.56 +/- 0.15 pW/cell, respectively, not significantly different from that in the controls. Consistently, there was no significant difference between patients with subclinical hyperthyroidism (N = 5) and controls (N = 5) with regard to lymphocyte energy production as calculated from separately measured oxygen consumption rates in vitro, 1.36 +/- 0.20 and 1.56 +/- 0.12 pW/cell, respectively. Thus microcalorimetry seems to be suitable for studying the influence of thyroid hormones on cellular metabolism. Subclinical thyroid dysfunction does not seem to alter the overall rate of lymphocyte metabolism. PMID- 2220261 TI - Epidermal growth factor in mice: effects of estradiol, testosterone and dexamethasone. AB - To clarify the influence of steroids on the metabolism of epidermal growth factor, we studied the effects on its concentrations in adult male and female mice of 1. gonadectomy, 2. postgonadectomy treatments with estradiol and testosterone, and 3. treatment with dexamethasone. We also measured its mRNA levels in submandibular salivary glands and kidneys after ovariectomy. After gonadectomy, the male mice had 1.4-fold higher mean epidermal growth factor concentration in the urine than the female, in contrast to a 1.5-fold reverse difference in intact mice; the female mice had 2.5-fold higher concentration in the submandibular glands than the male animals, in contrast to a 4.5-fold reverse difference in intact mice. The kidney sex difference of intact mice (male greater than female) was abolished. In both gonadectomized sexes, treatment with testosterone increased the concentration of epidermal growth factor in plasma and the submandibular gland; treatment with estradiol increased the concentration in urine and decreased it in the submandibular gland. Treatment with dexamethasone decreased the concentration of epidermal growth factor in plasma of the male mice, and in urine of the female mice, thus decreasing the sex differences. In the submandibular gland and the kidneys, dexamethasone increased the concentration. The mRNA levels were higher in the submandibular gland and lower in the kidneys in the ovariectomized than in the intact female mice. The effects of sex steroids on epidermal growth factor concentrations are mediated through modulation of its gene activity. Testosterone has an increasing and estradiol a decreasing effect in the submandibular gland. Estradiol has also an increasing effect in the kidneys. PMID- 2220259 TI - Physical and psychological capabilities during substitution therapy with recombinant growth hormone in adults with growth hormone deficiency. AB - In a double-blind cross-over study with recombinant methionyl growth hormone (GH) and placebo during 12 weeks, the effect of GH substitution therapy (0.5-06 IU.kg 1.week-1) on physical performance, muscle strength, bone mineral density, and mood and cognitive functions was investigated in 6 GH-deficient adults. During GH substitution serum concentrations of insulin-like growth factor-I and procollagen III peptide increased in all 6 patients, whereas concentrations of serum urea decreased. Five of the patients identified the GH period and reported improved well-being with increased mental alertness and vitality and improved physical capacity and muscle strength. There was, however, no change of the isokinetic muscle strength during GH substitution therapy, and the working capacity on the bicycle ergometer was just slightly improved in some patients. The bone mineral density was low and unchanged in all patients. Mood and cognitive functions did not change during GH therapy. A reversible fluid retention was observed in one patient during the GH period. In conclusion, short-term GH substitution therapy to GH-deficient adults induced a subjective improvement of general well-being. Longer treatment periods will be necessary to establish the effect on physical capacity, muscle strength, bone mineral density, and mood and cognitive functions. PMID- 2220262 TI - Characterization of cytosolic female rat liver receptors of the lactogenic type. AB - Some properties of cytosolic receptors of the lactogenic type from female rat liver were studied and compared with those of membrane-bound (microsomal) receptors. The association constant between the cytosolic receptors and human growth hormone was 2.2 l/nmol, which was not significantly different from the value obtained for the microsomal receptors (3.6 l/nmol). Since unlabeled hGH and human prolactin, but not bovine growth hormone, displaced [125I]hGH bound to receptors from both sources, the cytosolic receptors, like the microsomal receptors, must be lactogenic. Furthermore, the cytosolic receptors were recognized by a monoclonal antibody raised against microsomal receptors from female rat liver. However, covalent cross-linking of cytosolic receptors to [125I]hGH and subsequent sodium dodecyl sulphate electrophoresis gave a single band corresponding to a molecular weight of 42,200 (after subtraction of the molecular weight of hGH), which differs significantly (p less than 0.01) from the values determined for the two distinct bands given by the microsomal fraction. Moreover, upon molecular sieve chromatography the receptor activity in the two fractions appeared at significantly (p less than 0.05) different elution volumes. These results show that the cytosolic and microsomal receptors have some structural features in common but are definitely not identical. PMID- 2220268 TI - [Plasma membrane separation. A therapeutic possibility in thyrotoxic crisis]. AB - A case of thyroid storm is presented, successfully treated with a combination of antithyroidal drugs and plasma exchange. A 280% separation removed 447 micrograms T4 and 12 micrograms T3. During separation, the elevated T4 and T3 values returned to normal. Basic concepts of plasma membrane separation investigated by plasma and whole body counting after administration of 131I-T4, as well as radioimmunoassay measurement of thyroid hormones in plasma and separate are discussed. PMID- 2220265 TI - [Bier's occlusion. An unjustly neglected therapeutic possibility in resistant tissue defects of the extremities]. AB - The retrograde intravenous pressure infusion into an arterially occluded segment of an extremity (Bier's technique) is the most effective method to achieve maximal tissue concentrations of a drug. This was proven by nuclear medical examinations. By application of contrast-medium it was shown that the injected fluid penetrates in a retrograde direction into the foot inspite of primarily intact valves. A second important mechanism of action is the haemodynamic consequence of an arterial occlusion which is characterized not only by an immediate reactive hyperaemic response but also by a delayed increase of blood flow after several days. Favourable clinical results were obtained with antibiotics in infected gangrene of the feet or in necrotizing erysipelas and with urokinase in resistant leg ulcers. PMID- 2220264 TI - [Assessment of different clearance mechanisms of the lung using factor analysis]. AB - Measurement of epithelial clearance over the lungs is always influenced by mucociliary transport since the lung is a 3-dimensional organ where ciliated and respiratory epithelia overlap. Factor analysis provides factor images and time activity curves of extracted physiological factors corresponding to specific structures, even if these structures overlap. In 16 inhalation studies of 99m Tc DTPA aerosol, factor analysis always extracted 2 factors with opposite temporal behavior, one corresponding to epithelial and one to mucociliary transport. Clearance rates measured over the lungs were significantly lower than epithelial transport-related factor curve values (1.35%/min vs 2.2%/min), but were identical with the clearance rates of the sum of both factors plus factor background. Factor analysis allows quantitative assessment of epithelial transport without interference of other clearance mechanisms and should be evaluated further in different pulmonary disorders. PMID- 2220263 TI - Calcitonin causes a sustained inhibition of protein kinase c-stimulated bone resorption in contrast to the transient inhibition of parathyroid hormone-induced bone resorption. AB - Calcitonin is a well known inhibitor of osteoclastic bone resorption, both in vivo and in vitro. However, it is also known that calcitonin has only a transient inhibitory effect on bone resorption. The mechanism for this so-called "escape from inhibition" phenomenon is not clear. In the present study, the inhibitory effect of calcitonin on phorbol ester-induced bone resorption was examined in cultured neonatal mouse calvaria. Bone resorption was assessed as the release of radioactivity from bones prelabelled in vivo with 45Ca. Two protein kinase C activating phorbol esters, phorbol-12-myristate-13-acetate and phorbol-12,13 dibutyrate, both stimulated 45Ca release in 120-h cultures at a concentration of 10 nmol/l. Calcitonin (30 nmol/l) inhibited phorbol ester-stimulated bone resorption without any "escape from inhibition". This was in contrast to the transient inhibitory effect of calcitonin on bone resorption stimulated by parathyroid hormone (10 nmol/l), prostaglandin E2 (2 mumol/l), and bradykinin (1 mumol/l). Our results suggest that activation of protein kinase C produces a sustained inhibitory effect of calcitonin on bone resorption. PMID- 2220267 TI - [Immunoscintigraphic follow-up studies with the 99m-Tc marked monoclonal anti-CEA antibody BW 431/26]. AB - Repeated immunoscintigraphy with murine monoclonal antibodies was performed in only few patients because of developing HAMA (Human Anti Mouse Antibodies) and therefore high risk of allergic reactions. Patients with HAMA, which could be observed in about 26% after immunoscintigraphy, show high liver-spleen uptake of labeled monoclonal antibodies in further examinations in some cases. PMID- 2220266 TI - [Blood-pool-SPECT for imaging portosystemic collaterals in portal hypertension]. AB - In 46 patients, 26 male and 20 female, age from 32 to 71 years (mean 47.4 +/- 11 years) a bloodpool-scintigraphy (BPS) with SPECT (single photon emission computed tomography) was performed. The in-vivo labelling of the erythrocytes with pyrophosphate and Tc-99m was performed in the usual way. The SPECT investigations were performed with a digital Anger-Camera (Elscint; Apex 401). In 14 patients without collaterals BPS was performed to compare the method with patients with liver diseases and collaterals. 29 patients with liver cirrhosis and portal hypertension were investigated with the BPS and additionally a scintisplenoportography (SSP) was performed. In patients with only cephalad collaterals all the results were concordant. In just 1 patient with cephalad and caudad collaterals we found a discordant result. In 8 patients we performed BPS, SSP and a katheterangiography (KA). Taking the KA as the "golden standard" we found a concordant result with the 3 methods in all patients with cephalad collaterals. In patients with cephalad and caudad collaterals we once found a discordant result with the SSP and twice with the BSP. In 2 patients the patency of surgical shunts were proved. 2 patients after sclerosis of the oesophageal varices have been proved by BPS and SSP and both patients showed good therapeutical results. PMID- 2220271 TI - [The 21st annual meeting of the Austrian Society for Internal Medicine. Abstracts]. PMID- 2220272 TI - A service to members: the QA consultant. PMID- 2220270 TI - [Nuclear medicine measurement of the contractile activity of the stomach antrum using factor analysis]. AB - The motor activity of the gastric antrum is difficult to record by manometric means and scintigraphic methods have proved unsatisfactory so far as no consistent relationship between antral contractile activity and gastric emptying rate could be detected. We investigated, using data recorded in 16 healthy human subjects after the ingestion of a semisolid standard meal, whether a newly developed method employing factor analysis would yield more meaningful and reproducible results. Factor analysis was applied to sequential scintigraphic images (3-s frame time) of the gastric antrum. The computed factor images and the respective factor curves are representative of distinct dynamic structures of the antrum. From the more or less sinusoidal excursions of the factor curves, which exhibited the 3 cycles per minute frequency characteristic for the stomach, amplitude, frequency and propagation velocity of antral contractions can be calculated. The amplitudes of the factor curves were used to calculate a contraction index. This contraction index was found to be correlated significantly negatively with the gastric half-emptying time of the ingested meal. The employed factor analytical approach thus seems a promising tool to further investigate the role of antral contractility in the process of gastric emptying. PMID- 2220273 TI - The standards review project. PMID- 2220275 TI - Law and the abused woman. PMID- 2220274 TI - Caring for the disoriented older person: the family caregiver's perspective. PMID- 2220276 TI - Oncology nurses: affecting the journey. PMID- 2220278 TI - Is quality assurance dead? PMID- 2220281 TI - Law and the abused woman. Part two. PMID- 2220277 TI - 1991 75th anniversary AARN: our history--a proud heritage. The 1930's--dirty and depressing. PMID- 2220280 TI - Pain corner: chronic pain? Have you considered the stepwise approach? PMID- 2220279 TI - An ethnography of the spinal cord injury unit. Part one. PMID- 2220269 TI - [Clinical significance of Tl-201/Tc-99m subtraction scintigraphy as a parameter for surgical indication of cold struma nodules]. AB - In a retrospective study Tl-201/Tc-99m subtraction scintigraphy (method acco. to Ferlin et al.) was performed in addition to Tc-99m scintigraphy, sonography and fine needle puncture in 400 patients. Postoperative histological evidence was available of all patients (carcinomas [n = 31], follicular and oncocytic adenomas [n = 235], nodular hyperplasia, Hashimoto's thyroiditis, Riedel's struma and de Quervain's thyroiditis [n = 134]). With regard to possible malignancy the sensitivity, in case of positive Tl-201 uptake was 85%. As however, adenomas also have a high tendency towards isolated Tl-201 uptake, the specificity for malignant growth was 62%. Thus Tl-201/Tc-99m subtraction scintigraphy is well suited as a criterion to exclude thyroid carcinomas; on the other hand, a positive Tl-201 uptake is not a fail-safe indication of malignant processes. At best it suggests the occurrence of autonomous growth and can thus, in addition to sonography and fine needle biopsy, serve as an aid in the decision as to whether surgical intervention is indicated. PMID- 2220282 TI - Medication administration. PMID- 2220283 TI - Background paper regarding abuse of nurses in the workplace. PMID- 2220286 TI - Early changes in the rat pancreatic B cell size induced by glucose. AB - The perimeter, cell area and volume density (Vvi) of B cells and exocytotic images present in these cells were measured in rat pancreas perfused with 3.3 or 16.6 mM glucose. Four minutes after the beginning of 16.6-mM glucose perfusion and coincident with the appearance at the apex of the first phase of insulin secretion, all these parameters underwent a significant increase. The changes observed in the perimeter, the cell area and the Vvi of B cells suggest an increase in their surface area. An imbalance in the rate of endocytosis:exocytosis processes with a relative predominance of the latter would increase the length of the plasma membrane and could be responsible, at least partly, for the changes in the B cell size. PMID- 2220284 TI - Comparing the somal size and nuclear positions of the monkey stellate and coeliac ganglion cells. AB - The stellate and coeliac ganglia of 2 Macaque monkeys were cut serially at 1 micron thickness and analysed. Results from the analysis of 82 stellate and 60 coeliac ganglion cells in 1 monkey show that in cross-sections, the neuronal nuclei may be eccentric, centric or nearly centric and remain so throughout the longitudinal extent of the neuron. In both ganglia, the majority of neurons possess eccentric nuclei, but in the coeliac ganglion, the percentage of neurons with centric and/or nearly centric nuclei is higher (41.7%) than that in the stellate ganglion (26.3%). While 5% of neurons in the coeliac ganglion are binucleated, no binucleated neurons were found in the stellate ganglion. The somal size ranges of the stellate (10-39 microns) and the coeliac (14.5-45 microns) ganglion neurons as obtained from both monkeys are quite close. The percentage frequency distribution of the stellate ganglion neurons in monkey 1 was also quite similar to that of the coeliac ganglion neurons. It is concluded that different neuronal size is not likely to be associated with different target organs. PMID- 2220287 TI - [Ultrastructure of the substantia spongiosa of the femur head and talus]. AB - The results of the SEM examination of the zone between the cartilage and the spongeous substances are described precisely. For the first time, W. Lierse examined the 'tensulae' of calcium-collagen lamellae by light microscopy. The examination of this zone was initiated by the fact that the hydrodynamic flow can take place in the calcified zone of the cartilage which is filled with synovial fluid and that the calcified zone adheres to the subchondral substantia corticalis. The subchondral corticalis is characterized by funnel-like indentations with a high number of calcium-collagen and chondrocyte 'tensulae' which are up to now uncounted. The special aim was to locate the separation of the space of adipose and arterial supplies. PMID- 2220288 TI - Comparative electron microscopy of chorio-allantoic placental barrier in some Indian Chiroptera. AB - In the present study the comparative ultrastructure of the definitive chorio allantoic placental barrier has been studied in considerable detail in six species of bats, representing six different families and both suborders of Chiroptera, by electron microscopy, and these species illustrate different kinds of interhaemal membranes met with among bats. The definitive chorio-allantoic placenta of Rousettus leschenaulti is haemodichorial, since the syncytiotrophoblast and cytotrophoblast layers are present to term. The fine structure of the placental barrier in the labyrinth of the definitive placenta of Rhinopoma hardwickei hardwickei is essentially endotheliomonochorial due to the presence of a single layer of cytotrophoblast and maternal endothelial cells. The placenta of Taphozous melanopogon, examined electron-microscopically in the present study, shows a thick maternal endothelium, a continuous interstitial membrane and the presence of a single layer of syncytiotrophoblast. The placenta of Megaderma comprises a typical endotheliochorial labyrinth and the presence of two layers of trophoblast. In Rhinolophus rouxi, the mature placenta during advanced pregnancy resembles that of Megaderma, its labyrinth containing large maternal capillaries with maternal endothelial cells and the two layers of trophoblast. Finally, the placental barrier of Hipposideros fulvus fulvus is haemodichorial due to the presence of two layers of trophoblast and the absence of maternal endothelial cells. PMID- 2220289 TI - Ultrastructure of interstitial cells of Cajal at the gastro-oesophageal junction of the monkey (Macaca fascicularis). AB - The ultrastructure of the interstitial cells of Cajal (ICC) in the oesophagus of the monkey resembled that described in the oesophagus of other mammalian species but differed in their paucity and almost lack of smooth endoplasmic reticulum, caveolae and filaments. The plasmalemma of the ICC was in close contact (20- to 30-nm gaps) with that of smooth muscle cells. This may occasionally take the form of a desmosome, but gap junctions have not been observed. Vesiculated axon profiles, containing large granular or agranular vesicles were in close contact (20- to 30-nm gaps) with the plasmalemma of ICC. In a few vesiculated profiles a presynaptic density could be recognized. The intercalation of the ICC between the vesiculated axon profiles and the smooth muscle cells suggest a role in oesophageal motility. Between 3 and 21 days following bilateral vagotomy some ICC showed regressive changes such as increased electron density and shrinkage of the cytoplasm, crowding of the organelles and dissolution of the nuclear chromatin material. Axon profiles in the vicinity of the affected ICC contained glycogen granules suggesting injury. In late stages, the number of ICC and smooth muscle contacts was reduced. The results suggest that the vagus nerves exert a trophic influence on the ICC and that the intercellular relationships between ICC and smooth muscle cells possess a degree of plasticity. It is tentatively suggested that these vagal effects may be mediated via the oesophageal myenteric ganglia. PMID- 2220290 TI - Acetylcholinesterase activity of developing muscles in the lower limb of the rat. AB - A cytochemical study of acetylcholinesterase was done in the lower limb of the prenatal rat and in the gastrocnemius muscle of the postnatal rat. Between 15 and 17 days of gestation, mesenchymal cells constituting the muscle primordia are characterized by the presence of enzyme activity in their rough endoplasmic cisterns and nuclear envelopes, while those involved in the formation of the neocapillary and cartilage do not show enzyme activity. This suggests that mesenchymal cells destined to myogenic cells actively produce acetylcholinesterase in a limited period, which may play a role in cellular aggregation and fusion during the muscular morphogenesis. Cytochemical findings as to extensive networks of secondary synaptic folds of the neuromuscular junctions and invaginations of the sarcolemma in the extrasynaptic regions are also illustrated in the differentiating gastrocnemius muscles. PMID- 2220293 TI - Myocardial fiber architecture in the human heart. Anatomical demonstration of modifications in the normal pattern of ventricular fiber architecture in a malformed adult specimen. AB - Ventricular myocardial fiber architecture has been considered an important factor in heart dynamics. Most anatomical studies however have focussed on the analysis of normal hearts. The present study compares ventricular myocardial fiber architecture patterns in dissections of 5 normal hearts and a malformed human heart with membranous ventricular septal defect, overriding right aorta, pulmonic stenosis, with absent pulmonary valve and hypertrophied right ventricle. Qualitative and quantitative changes in ventricular myocardial fiber architecture were noted in the malformed heart. PMID- 2220291 TI - The milky spots on the chest wall in newborns. AB - The histologic properties of pleural adipose organs were studied in 14 newborns. These organs contain milky spots, in which lymphocytes, macrophages and plurivacuolated fat cells are present. The milky spots have a mesothelial covering, persist to the age of 9 months and seem to act as defence devices and a site of fluid exchange. PMID- 2220294 TI - Early evaluation of postmenopausal hormonal steroid therapy by scanning electron microscopy of the uterine epithelium. AB - Scanning electron microscopy has been used in a preliminary study to evaluate the value of steroid replacement therapies in restoring uterine epithelium in postmenopausal patients. All therapies resulted in increased epithelium over controls, but one regime was markedly better than others. PMID- 2220296 TI - Lymphocyte blastogenesis and lepromin reactivity in leprosy patients and their parents. AB - To determine whether there is an inherited familiar trait linked to the lymphocyte blastogenesis test (LTT), under stimulation with PHA, lepromin and Mycobacterium leprae in culture medium containing autologous plasma, this test was carried out in patients with the polar forms of leprosy and their parents. The lepromin reaction was also studied in the patients and their parents because, since the test is negative in lepromatous (L) patients and a greater proportion of negativity is detected among their relatives, it might be assumed that the lymphocytes of these individuals could have a lower tendency towards blastogenesis than lymphocytes of tuberculoid (T) patients and their relatives. Thirty individuals were studied, ten of them being leprosy patients (4 L and 6 T) and the remaining their parents; 115 LTT, including control and stimulated cultures, were performed. In the limited number of patients and parents studied, the results showed that mothers of either L or T patients displayed a similarly low response to the stimulants M. leprae and lepromin. The lepromin reaction was negative in all L patients and positive in 3 out of 8 parents, as well in all the T cases and their fathers. Fathers and their T descendants were lepromin positive and there was a certain relationship between this reactivity and blastogenesis. This might suggest a possible inherited familiar trait related to a relative degree of resistance. However, further evidences from studies with larger number of subjects are required to support this hypothesis. PMID- 2220295 TI - [Late reversal reactions in leprosy]. AB - Since the application of short duration multidrug therapy (MDT) in leprosy, it has been reported that reversal reactions (RR) may occur after withdrawal of treatment. Surprisingly, such "late reversal reactions" have quite never been described after monosulphonotherapy. Such RR, especially in endemic areas, may represent diagnostic and therapeutic difficult problems. We report 5 cases of late RR. In 4 cases (1 BT patient and 3 BL-LLs patients), the RR occurred 1 month 1/2 to 3 years after cessation of MDT. In the last case (form LLs), the RR happened 6 months after that a 14 years monosulphonotherapy has been stopped. These observations strengthen the need of a complete clinical, bacteriological and immunological evaluation at the time of the diagnostic, more useful than a single bacteriological study, to differentiate late RR from relapses. Moreover, the last case confirms that late RR may occur after monosulphonotherapy. PMID- 2220292 TI - Size of the fibrillar centres of the nucleoli in the supraoptic nucleus of the rat taking the Swiss cheese effect into account. AB - The size of the fibrillar centres (FC) in nucleoli was investigated taking the Swiss cheese effect into account. Electron microscopy was performed on the neurons of the rat supraoptic nucleus after the secretion of vasopressin had been fully suppressed by water load, after the secretion had been stimulated by water deprival and in normal rats with water ad libitum. When the secretory activity was suppressed from a normal level to approximately no activity, the size of the individual FC was doubled. Moreover, with increasing secretory activity the number of FC per cell increased. PMID- 2220297 TI - [Evaluation of 7 years of systematic surveys of leprosy in Morocco]. AB - Between 1980 and 1987, 12 systematic surveys were made on a population of 254,979 people, of whom 236,868 were actually examined (92.61%). 422 suspected cases were identified i.e. a global detection rate of 1.66% of which only 241 reported to Ain-Chock Hospital for further tests (55%). Out of these 241 suspected cases, 217 proved as having leprosy, i.e. a 90% correlation between the clinical suspicion and the biological identification. The 181 suspected cases who never reported to the hospital and the 16 leprosy patients whom we lost sight of constitute as a whole 46.68% of the suspected cases first identified. This shows an obvious lack of coordination between the local Authority and the medical service. The 185 confirmed cases of leprosy are shown in the table below and compared with those of the Central Statistical Office. PMID- 2220285 TI - Chronic hyperglycemia in experimental diabetes mellitus of short duration does not contribute to muscle capillary basement membrane thickening. AB - The effect of chronic hyperglycemia on the relationship of nonenzymatic glycation and capillary basement membrane thickness in muscle was studied in streptozotocin induced diabetic rats early in the course of diabetes mellitus. Diabetic animals were placed on either standard (24%) or restricted (8%) protein diet. The animals on 8% protein diet had elevated glycated hemoglobin levels (p less than 0.01) and increased levels of nonenzymatic glycation of basement membrane (p less than 0.01) as compared to insulin-treated diabetic (euglycemic), age-matched control, and streptozotocin-injected nondiabetic animals also on 8% protein diet. In contrast, diabetic animals on restricted (8%) protein diet and those on standard (24%) protein diet showed no statistical differences between them with regards to the above parameters. Moreover, there were no statistical differences among diabetic and control animals on either 8 or 24% protein diet with respect to muscle capillary membrane thickness. Even though the peripheral muscle biopsy study of capillary basement membrane is less invasive than kidney biopsy, the results of this study suggest that neither nonenzymatic glycation nor basement membrane thickness can be utilized as predictors of renal dysfunction during early onset of diabetes mellitus. PMID- 2220299 TI - A case of isolated tuberculoid leprosy of brachial cutaneous nerve. AB - The author relates a rare case of cutaneous-brachial nerve mononeuritis in a Hansen's disease patient, presenting a pure neural tuberculoid form, with spontaneous drainage of abscess. PMID- 2220302 TI - [Necessary methodologies for research advancements in leprous neuritis]. PMID- 2220301 TI - Histological changes in tuberculoid leprosy after fixed duration multidrug therapy for six months. AB - The length of treatment advocated for leprosy has been very long and arbitrary. During the past few years, attempts have been made to reduce the length of treatment required. World Health Organization (WHO) has recommended six months therapy for paucibacillary leprosy. The present study was undertaken to see the extent of histological changes that occur with this therapy. Thirty four untreated tuberculoid (TT/BT) leprosy patients were biopsied initially and after completion of fixed course of this treatment. Clinically, 50 percent of the patients showed regression of disease activity at the end of six months. Morphology of the lesions was studied, in clinically active and inactive cases on completion of therapy. It was found that after six month's therapy, histology of the lesions was similar, whether the case was active or not. After the prescribed treatment, biopsy showed marked reduction in the extent of granuloma, along with significant increase in lymphocytes and a increase in epithelioid cells in these granulomas. PMID- 2220300 TI - Isolation and characterization of infiltrates in the nerves of patients with neuritic leprosy. AB - A study was done on the characteristics of infiltrating cells in the nerves of 9 patients with pure neuritic leprosy, by preparing a single cell suspension. The patients had no skin lesion. Histopathological examination revealed that 2 of the 9 nerves showed granulomas characteristics of tuberculoid leprosy, while the remaining 7 had features of lepromatous granulomas. In the nerves showing tuberculoid granulomas, a high proportion of lymphocytes were T cells as they formed rosettes with sheep erythrocytes and only a few percent were EAC rosette forming cells. On the other hand, the nerves showing lepromatous granulomas contained only occasional lymphocytes which formed E and EAC rosettes. Macrophages from the granulomas of all the nerves were esterase positive, peroxidase negative, contained M. leprae and did not exhibit C3 surface receptors. PMID- 2220303 TI - The demystification of leprosy: a multifactorial problem. AB - Abolishment of misbeliefs and misconceptions, unfounded fear and prejudice are factors as important in leprosy control as prevention, early detection and therapy. Concrete measures of demystification are proposed. Identify and divulge the absolute truth about leprosy. Calling leprosy "Hansen's disease" did not result in demystification. Patients know that the two terms are identical. Treating them as human beings attracts more patients to the healers than the Hansenologian ritual. Contrary to statements, no major advances are being made in the field of bacteriology, immunology, molecular biology, mode of transmission and epidemiology of leprosy. Not a single new drug has been discovered in 26 years. Vaccination is a dubious venture. The question arises as to whether the right priorities are promoted in leprosy research. Cultivation of the leprosy bacillus is the sine qua non of any further progress. This field of research is a lost and totally neglected priority. Consequently we have no pharmacological model for badly needed of ultrapotent antileprosy drugs. Syphilis is now cured with a single dose of penicillin. A drug as potent against leprosy should not be a mission impossible if an appropriate pharmacological model--the in vitro culture--is available. The multifactorial problem of demystification is a difficult but not an impossible task. Less sensationalism, more real progress in research, selecting the right priorities, achieving the "ultimate drug", shelter, food, shoes, soap and broom for every human on this planet constitute the road to demystification. PMID- 2220298 TI - [The evaluation of an anti-leprosy program in Ueles (1975-1989)]. AB - Foperda, who took over and continued the work initiated in 1924 by the Congo Red Cross, is responsible for the programme of fight against leprosy in the Ueles region (Zaire). Important results have been obtained since 1975 in the framework of a specialised medical service. These results are exposed and discussed herebelow. The evolution of the endemic leprosy in the region under survey allows to contemplate new trends for the pursuit of the programme in the coming years (controlled integration within polyvalent health services). PMID- 2220306 TI - Improved energy kinetics following high protein diet in McArdle's syndrome. A 31P magnetic resonance spectroscopy study. AB - A patient with McArdle's syndrome was examined using bicycle ergometry and 31P NMR spectroscopy during exercise. The patients working capacity was approximately half the expected capacity of controls. Muscle energy kinetics improved significantly during intravenous glucose infusion and after 6 weeks of high protein diet. During intravenous infusion of amino acids, no changes in working capacity could be detected. No decrease was seen in intracellular muscle pH during aerobic exercise. A significant decrease in muscle pH during aerobic exercise was detected in all controls. PMID- 2220310 TI - Forceps delivery as a risk factor in epilepsy: a comparative prospective cohort survey. AB - Three-hundred and eighty-one children born with forceps delivery and 372 with normal delivery were followed up for 4-7 years. More children in the forceps group developed seizures than in normal group, i.e. 22:10. This was statistically significant (P less than 0.05). A prolonged follow-up is necessary for further observations. PMID- 2220304 TI - Multiple sclerosis in Spain: an epidemiological study of the Alcoy health region, Valencia. AB - Alcoy is a defined health region in eastern Spain, at 3 degrees E-38 degrees N, with a single neurology department and includes 33 towns with a total population of 133,915 inhabitants. We have evaluated the prevalence and incidence of multiple sclerosis (MS) by analysing this region. Six new cases have been detected (2.24/100,000/year) and the prevalence rate was 17.17/100,000, the highest in Spain at the moment. However, we found an irregular distribution in the different towns in so far that 15 of our 23 patients lived in a particular subregion, which means a prevalence of 44.59/100,000. Our study shows that the area of Alcoy is a medium MS risk region according to the thesis of Kurzke, although high MS areas may be found, thus confirming that MS distribution in southern Europe is not uniform. PMID- 2220309 TI - Ventricle brain ratio in the clinical course of HIV infection. AB - As part of the computerized tomographic assessment of an unselected group of 47 patients in different stages of HIV infection we determined the ventricle brain ratio (VBR) and the width of several cortical sulci. We compared the findings for subgroups of patients defined by their stage in the Walter Reed Staging Classification. There was a significant increase in VBR only in the subgroup of patients with manifest acquired immune deficiency syndrome (AIDS) (WR 6). The findings are discussed in connection with the question of the likelihood that dementia will develop even in stages of HIV-infection preceding AIDS. PMID- 2220308 TI - Auditory ear extinction in lacunar syndromes. AB - A dichotic listening test was administered to 28 patients with lacunar syndromes in order to contribute to the investigation of the subcortical route of interhemispheric auditory pathways. Topographic study showed that lesions in the external capsule or in the anterior limb of the internal capsule in both hemispheres produced left ear extinction. The possibility that some of the auditory fibres travel through the external capsule, as well as the anterior limb of the internal capsule, before crossing the contralateral cerebral lobe is suggested. PMID- 2220312 TI - Thermal discrimination thresholds: a comparison of different methods. AB - Thermal testing was carried out on 55 healthy subjects in order to establish normal results and reproducibility of warm and cold thresholds. Diurnal variations of thresholds were investigated in a further 30 normal subjects. Then the sensitivity of different testing procedures was investigated in 33 patients with diabetes mellitus, but without severe polyneuropathy. Forced choice testing takes 6 times longer than the method of limits, and the results are not considerably different. It is thought that the forced choice algorithm does not provide a method for clinical routine. Another new approach, the double random staircase method, may help to exclude bias without taking too much time. PMID- 2220313 TI - Therapy and survival of adult patients with intracranial glioma in a defined population. AB - During the 3 years 1978-1980 146 adult patients with intracranial glioma were diagnosed in the Province of Uusimaa in southern Finland. The median survival of all patients was 15 months, of glioblastoma (n = 41) 5.1 months, of anaplastic astrocytoma (n = 29) 12.4 months, of benign grade I-II astrocytoma (n = 30) 93.5 months, of other glioma 82.9 months (n = 27), and of probable glioma 9.8 months (n = 19); 22 patients are still alive 8.9-11.9 years after diagnosis. The patients who were 15-44 years of age at the time of diagnosis survived 75.4 months in the median (n = 58), 45-64 years 10.5 months (n = 61) and 65 years or older 4.8 months (n = 27); 96 patients were operated, 89 received radiotherapy and 34 chemotherapy. According to the proportional hazards' model, follow-up time, age and histological type of tumor were statistically highly significant in explaining differences in survival. PMID- 2220307 TI - Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. AB - The Wechsler Intelligence Scales for Children was applied to 64 epileptic children and 60 healthy subjects; patients followed chronic treatment with valproic acid (n = 32) or phenobarbital (n = 32). None of the children suffered mental retardation or neurological abnormalities. The test was repeated after a 9 12 month interval: 26 of the valproate treated children and 23 of the phenobarbital-treated children performed the second evaluation. At baseline, total, verbal and performance IQ scores of children receiving phenobarbital were lower than those of controls. When the results of the first and the second tests were compared, a significant increase in IQ scores was detected among controls and patients treated with valproic acid, but not among phenobarbital-treated patients. It is concluded that long-term phenobarbital therapy induces a significant impairment in learning ability whereas long-term valproate therapy does not exert a noticeable noxious effect at this respect. PMID- 2220316 TI - Novel therapeutic strategies for dementia diseases. Proceedings of the Nobel Medicare Research Forum. Sweden, August 21-23, 1989. PMID- 2220317 TI - Role of catechol autooxidation in the degeneration of dopamine neurons. PMID- 2220314 TI - Transient global amnesia and Raynaud's phenomenon in scleroderma. AB - Transient global amnesia (TGA) is a well-recognized clinical entity, but its pathophysiology and prognosis have remained arguable. We reported that a 63-year old woman with scleroderma developed two TGA episodes. The patient sometimes suffered from headaches when Raynaud's phenomenon appeared in her fingers, but she did not experience further cerebrovascular events. This case suggests that the unique clinical presentation of this syndrome may result from an ischemic event, possibly triggered by a vasospastic mechanism like Raynaud's phenomenon. PMID- 2220318 TI - The cholinergic system and the excitatory amino acids in Alzheimer's disease. PMID- 2220305 TI - Relation between thyroid and cardiac functions and the geriatric rating scale. AB - To assess the effects of thyroid hormone and cardiac function on senile dementia, relations between serum thyroid hormone concentrations, hemodynamic parameters and dementia rating scale scores were studied in 83 subjects aged 70 and over. Age and serum-free T3 concentrations had a significantly negative correlation in all subjects and in subjects without dementia, but not when analysed only in dementia subjects. Regarding the genesis of dementia, serum free T3 concentrations and cardiac index were both significantly lower in cerebrovascular dementia than in those without dementia. Moreover, subjects with cerebrovascular dementia showed significantly lower serum free T3 concentrations and cardiac index than those with senile dementia of Alzheimer's type in all age groups. These findings suggest that cognitive function is closely related to serum free T3 and cardiac function in subjects with cerebrovascular dementia and that serum free T3 concentrations may be a good indicator, reflecting health and cognitive status. PMID- 2220315 TI - Increased endothelin concentration in CSF from patients with subarachnoid hemorrhage. AB - A considerable quantity of endothelin-like immunoreactivity was demonstrated as present in the CSF of patients with subarachnoid hemorrhage. The endothelin levels in the CSF raised from 0.4 +/- 0.2 (Mean +/- SD) pmol/L at Day 0-1 to 2.2 +/- 0.6 pmol/L at Day 6 and the levels decreased gradually. The result suggest that endothelin may contribute the generation of vasospasm often observed in subarachnoid hemorrhage. PMID- 2220319 TI - Alzheimer disease: the clinical syndrome; diagnostic and etiologic importance. PMID- 2220321 TI - THA, a putative drug in the treatment of Alzheimer's disease? PMID- 2220320 TI - Gangliosides and nerve growth factors in Alzheimer's disease. PMID- 2220323 TI - Plasticity of memory functioning in normal aging and Alzheimer's disease. PMID- 2220324 TI - Is good care the best treatment for the Alzheimer patient? PMID- 2220328 TI - Progression of posterior approximal carious lesions in Norwegian teenagers from 1982 to 1986. AB - The purpose of the present study was to assess the progression rate of approximal carious lesions in Norwegians aged 14-18 years. Sixty-five subjects whose average age at base line was 14.9 years had one pair of posterior bitewing radiographs taken annually from 1982 to 1986. One examiner assessed all radiographs in chronologic order, recording degree of approximal caries. When a surface changed from one state to another, it was assumed to have changed at the midpoint between the two examinations. A total of 590 lesions were observed. Uncensored lesions took on average nearly 3 years to penetrate the enamel. Inclusion of right censored lesions by the Kaplan-Meier approach increased the uncensored estimate by approximately 20%. The average for doubly censored lesions was about 6.5 years. Low average rate of caries progression coupled with wide variations between lesions and among subjects suggests a need for individually prescribed recall routines. PMID- 2220322 TI - Molecular genetics of Alzheimer's disease. PMID- 2220325 TI - Recent progress in the characterization of the pathological hallmarks for Alzheimer's disease. PMID- 2220329 TI - Weekly variation in the acidogenic response of plaque. AB - The fall in plaque pH after sucrose rinsing was monitored once a week for 9 (8) weeks in succession, to measure the weekly variation in the magnitude of pH drop in the same subject. The plaque pH was measured with a touch electrode placed interdentally between the first and second premolar. The subject rinsed his mouth with 10% (w/v) sucrose solution, and the plaque pH was thereafter monitored for 40 min. The minimum plaque pH (pHmin), the change between starting and minimum pH (delta pH), and the resting pH value were determined. The pH values of the maxilla and mandible differed. No difference was seen between the right and left sides. As a rule, intraindividual variation was lower in terms of pHmin values than in terms of delta pH values. It was concluded that pH assessment with the touch electrode appeared to show a small weekly variation intraindividually and to be sensitive enough to test the acidogenic potential of foods, but only in the maxilla. PMID- 2220326 TI - The empty sella. A reappraisal of etiology and pathogenesis. AB - The empty sella turcica is defined as a sella which, regardless of its size, is completely or partly filled with cerebrospinal fluid. An empty sella of normal size is a frequent and probably normal finding in unselected autopsy series. In clinical series an empty sella usually appears enlarged and is often associated with a variety of clinical disorders, constituting the so-called empty sella syndrome. Several causes of an enlarged empty sella have been suggested: a congenitally missing (deficient) sellar diaphragm with or without altered cerebrospinal fluid dynamics, previous pituitary gland hypertrophy or the outcome of a pituitary tumor necrosis. Increased intracranial pressure will induce a sellar enlargement in some patients and, consequently, also the emptiness. This pathogenesis is, however, applicable only in a minority of patients with an empty enlarged sella. Data from the literature and from own studies suggest that the enlarged empty sellae and the associated findings in the majority of cases are caused by spontaneous necrosis of a previous pituitary adenoma. This theory explains the frequent presence of pituitary insufficiency, pituitary hypersecretion, and visual field defects in patients with an empty sella. Furthermore, it offers an explanation of the finding of an empty enlarged sella in some patients with non-traumatic cerebrospinal fluid rhinorrhea and probably also benign intracranial hypertension. Thus, an empty enlarged sella is a stage in the spontaneous course of some pituitary adenomas and the associated findings constituting the empty sella syndrome are an occasional part of the clinical presentation of pituitary adenomas. PMID- 2220327 TI - Effect of culture medium on acid production from sorbitol by oral bacteria. AB - The fermentation of sorbitol or glucose and the acid production by strains belonging to the genera Actinomyces, Lactobacillus, and Streptococcus isolated from the predominant sorbitol-fermenting human dental plaque flora were studied in cultures in complex or defined bacteriologic broths and in saliva-based broth. The growth yields of Lactobacillus and Streptococcus in the saliva-based media and of Actinomyces in the defined broth were poor. Addition of fermentable carbohydrate to the saliva-based broth favored the growth of Streptococcus and Lactobacillus but not that of Actinomyces. The results showed obvious differences in the capacity of oral bacteria to ferment sorbitol between cultures in saliva based and bacteriologic broths. Lactobacillus failed to utilize sorbitol when saliva was the only source of nutrients. Lower proportions of lactic and formic acids were formed from sorbitol by Actinomyces and Lactobacillus in the saliva based than in the bacteriologic media. The findings illustrate some mechanisms possibly involved in the interactions between sorbitol and dental plaque flora. PMID- 2220311 TI - Abnormal hemorheological parameters in vertebrobasilar-insufficiency. AB - Thirty-seven patients, aged 47 +/- 22 years, diagnosed suffering from vertebrobasilar insufficiency (VBI), underwent a hemorheological examination; 20% of these patients had no vascular risk-factor but none showed complete normal hemorheological findings. The distribution of hemorheological parameters was comparable to those in patients suffering from stroke or TIA. Abnormal were platelet-reactivity in 78%, plasma-viscosity in 57%, fibrinogen in 23%, red-blood cell-aggregation in 13% and hematocrit in 11% of all cases. To obtain more information on how to classify common clinical symptoms i.e. headache in combination with vertigo it may be useful to introduce hemorheological parameters as platelet-reactivity, plasma-viscosity, fibrinogen, in the further laboratory examination of those patients. PMID- 2220330 TI - Fixed restorations produced for recipients of dental prosthodontic treatment. A comparison between general dental practice and a dental school. AB - Fixed prosthodontic work ordered by general dental practitioners was examined through registrations made in commercial dental laboratories. A comparison was made with similar data from student files on fixed prosthodontic treatment at the University Clinic in Bergen, Norway, which is located in the same geographic area. The results indicated that the distributional pattern of fixed restorations within the dentition was much the same in the individuals attending the general dental practitioners as in those treated at the dental school. While the practicing dentists preferred metal-ceramics in most cases, most of the restorations inserted at the dental school were based on the metal-resin technique. PMID- 2220331 TI - Storage stability of solutions of pyruvic acid/glycine used in adhesive bonding. AB - The rate of deterioration of pyruvic acid/glycine solutions used as common pretreatment of enamel and dentin in the Gluma bonding technique was investigated. Bond strengths between composite resin and enamel/dentin were measured. The bonds were mediated by pyruvic acid/glycine solutions, applied from 0 to 6 months after the time of manufacture. Bond strengths to enamel varied between 8.6 and 13.5 MPa and to dentin between 6.2 and 18.0 MPa. The pH of the solutions rose slightly during the experimental period, but no statistically significant change in bond strengths was observed. PMID- 2220332 TI - A simple system for generating low-dosage mercury vapor for animal experiments. AB - A system using unlabeled, metallic mercury for generating low-dosage vapor for animal experiments is described. The system consists of four acrylic plastic chambers: one chamber containing the mercury source, one for mixing the mercury vapor with air, one exposure chamber, and one containing activated coal filters and mechanisms for regulating the airflow. The chambers are connected to each other by means of 80-mm-diameter polyvinyl chloride tubes reinforced with wire. Additional control and supporting equipment is also used. The system is easy to set up and requires minimal attendance during use. A standard deviation of 3-4% in the mercury vapor level during 6 h of exposure is typical. The conditions for the animals during exposure and the safety for the personnel during use are optimal. PMID- 2220334 TI - Validity of the radiographic assessment of ankylosis. Evaluation of long-term reactions in 10 monkey incisors. AB - The accuracy and sensitivity of radiographic assessments of reactive processes in dental tissues were evaluated by comparison of radiographs and histologic sections. Experimental lesions inflicted on the roots of 10 monkey incisors had been observed by means of serially obtained radiographs over a period of 315 to 370 days. The material was used for evaluation of radiographic assessment of ankylosis. For comparative purposes, assessment of the experimental lesion penetrating to the pulp and periapical radiolucency was added. True and falsely positive or negative recordings formed the basis for calculation of the accuracy and sensitivity of the radiographic assessment. The sensitivity, or the observers' ability to detect the actual changes, was high for pulp penetration, intermediate for inflammation, and low for ankylosis. PMID- 2220333 TI - An 11-year follow-up study of dental caries after discontinuation of school-based fluoride programs. AB - The purpose of the present study was to determine whether the caries-preventive effect of school-based programs with fluoride (F) mouthrinsing or toothbrushing was evident at the end of a post-treatment follow-up period of 11 years. Two groups of subjects examined at 14 years of age (born in 1960), who had participated in fortnightly F rinsing (n = 52) or in F brushing 4-5 times a year at school (n = 50), were re-examined radiographically and completed a questionnaire at age 25 years. A comparison group of 25-year-olds (n = 51) was also included. Analyses of variance showed that the benefits of participation in school-based F programs seem to have been lost. It appears that these caries preventive programs have delayed rather than prevented caries and that F toothpaste and other caries-preventive efforts have been insufficient to avert a substantial caries activity during the follow-up period. PMID- 2220336 TI - Prevalence and severity of occlusal tooth wear in a young Saudi population. AB - An epidemiologic investigation of the prevalence and severity of occlusal wear was carried out in a young Saudi population. Occlusal wear was evaluated on a tooth-by-tooth basis on study casts made for 206 dental students, using an ordinal scale. The reliability of the scale was assessed by percentage inter- and intra-observer concordance. The mean occlusal wear was high for the population studied. The sample presented the highest wear scores in the incisor region, maxillary canines, and mandibular molars. Comparison with other studies of similarly aged Western populations showed a more extensive pattern of wear in the present sample, pointing to the possible role of environmental influences. PMID- 2220335 TI - Comparison of three radiographic methods in screening of temporomandibular joint involvement in patients with psoriatic arthritis. AB - Fifty-three randomly selected subjects with psoriatic arthritis (PA) were examined radiographically by means of orthopantomography, transcranial radiography, and transmaxillary radiography. Two examiners graded the radiographic signs of flattening, osteophytes, erosion, and sclerosis. The findings obtained were then compared, to determine the best technique for screening of temporomandibular joint (TMJ) bone changes. Together the techniques showed definite (24%) and possible (6%) changes suggesting TMJ involvement in 31 (30%) of 106 joints. In all projections radiographic signs suggesting TMJ involvement were most frequent in the condyle. Erosion in the condyle was the most frequent finding. Agreement with regard to definite changes in the condyle was found in only one-third to half of the cases. It is concluded that in radiography of the TMJ in subjects with PA a combination of radiographic techniques should be used to obtain maximum information. However, orthopantomography is well suited for screening of TMJ involvement in subjects with PA. PMID- 2220338 TI - Introducing a new section, and a note on geography. PMID- 2220339 TI - Acta sixty years ago. A theory on the dominant follicle and uniovulation. PMID- 2220337 TI - The influence of dental amalgam placement on mercury, selenium, and glutathione peroxidase in man. AB - Amalgam restorations were inserted in eight healthy persons, previously unprovided with dental restorations, who had several severe carious lesions. The mean number of surfaces restored were 16.1 (range, 11 to 22). The total mean calculated amount of mercury inserted was 2.9 g (range, 1.5 to 4.3 g). Blood and urinary levels were measured on seven occasions during a 4-month period before and a 3-month period after amalgam placement. One and 3 months after placement, the P-mercury mean values were almost equal to the preplacement values (3.3 nmol/l). After placement U-mercury increased continuously; 3 months after placement a statistically significantly higher (p less than 0.05) mean U-mercury value (0.58 nmol/mmol creatinine) was found compared with the mean preplacement value (0.34 nmol/mmol creatinine). No statistically significant correlation was found between the P- and U-mercury concentrations and the total number of amalgam surfaces. Selenium levels in plasma and urine and erythrocyte glutathione peroxidase showed no systematic change of pattern. The results show that the insertion of amalgam fillings contributed to the U-mercury concentration, but apparently even more extensive amalgam therapy and/or longer exposure periods are needed to affect the P-mercury concentration. No negative effects on the P- and U selenium or the erythrocyte glutathione peroxidase levels could be found during the 3 months immediately after an extensive amalgam placement. The supplementary blood and urine analyses were not influenced by the insertion of amalgam fillings. PMID- 2220341 TI - Venous muscle pump function during pregnancy. Assessment by ambulatory strain gauge plethysmography. AB - The venous muscle pump function was quantitatively assessed through pregnancy weeks 16, 30, 38 and 3 months (week 53) following delivery, in 24 pregnant women who completed a normal pregnancy. A statistically significant increase was found in the mean venous reflux (P less than 0.01), which was restored to initial values postpartum. Expelled calf volume remained stable throughout pregnancy but increased following delivery. Venous outflow from the legs was significantly reduced in the third trimester. Subjective symptoms of venous insufficiency increased through pregnancy, but, these symptoms had virtually disappeared post partum, corresponding to the muscle pump normalization. No statistical correlation was found between venous muscle pump values and changes in hormone concentrations of estradiol, estriol and progesterone. It is suggested that venous insufficiency development in pregnancy is caused primarily by mechanical obstruction, or hormonal influence other than that of estradiol, estriol or progesterone. 17% (4.7-37%) of the women with a normal pregnancy developed a pathological venous muscle pump function. PMID- 2220342 TI - Epidermal growth factor (EGF) concentrations in amniotic fluid and maternal urine during pregnancy. AB - Epidermal growth factor (EGF) was measured in amniotic fluid and maternal urine from women undergoing amniocentesis for genetic studies (15-22 weeks' gestation, n = 36) and lung maturational studies (35-39 weeks' gestation, n = 20). Amniotic fluid EGF concentrations (mean +/- SD) were higher near term (87 +/- 71 pM) than mid-gestation (35 +/- 8 pM) (p less than 0.0001). Urinary EGF concentrations were higher near mid-gestation (53.9 +/- 30.8 micrograms EGF/g creatinine) than near term (33.4 +/- 14.1 micrograms EGF/g creatinine) (p less than 0.006). There was no correlation between individual amniotic fluid and urinary EGF concentrations. The amniotic fluid EGF concentrations correlated with gestational age. However, there was no relationship between EGF concentrations and pulmonary maturity studies or placental weight from the pregnancies studied near term. We conclude that the concentration of EGF in amniotic fluid increases towards term. The lack of correlation between amniotic fluid and maternal urinary EGF concentrations suggests that there probably is a different source of EGF in the two compartments and that EGF does not cross the placenta to any great extent. PMID- 2220340 TI - Duration of human singleton pregnancy. A population-based study. AB - We have analysed the duration of pregnancy for singleton births in Sweden during 1976-80 by means of data from the Swedish Birth Registry. Information, which was obtained from special forms with standard questions, include date of first day of last menstrual period (LMP) and whether that date was considered reliable or not. Recording was done prospectively, starting at the first antenatal visit. In 10% of cases the dates were labelled uncertain. Information on LMP and birth dates, parity, age of mother, sex of child, and/or mode of delivery was missing in 5.5% of the singleton cases, leaving 427,581 singleton births for analysis. In cases of reliable menstrual dates, the average duration from LMP to vaginal birth was 282 days (median), 281 days (mean) and 283 days (mode), remaining constant over the years of study. One standard deviation of the mean was approximately 13 days, varying slightly with age and parity. Ten per cent of these women gave birth post term (past 294 days). The duration of cesarean section births became shorter over the years, in spite of little change in cesarean section frequency (9.5% in 1976 7 and 10.9% in 1979-80). Mothers aged 35 and over tended to give birth 2 days earlier than those below 35. Second and subsequent children of mothers below 35 had slightly shorter gestations than first-borns. Boys were born earlier than girls, on average. When LMP was unreliable, the distribution of gestational lengths was wide. We also noted a seasonal rhythmicity in average duration of pregnancy, with consistent shortening in the month of December. PMID- 2220343 TI - Effects of intravenous terbutaline on maternal circulation and fetal heart activity. AB - The effects of terbutaline on maternal circulation and fetal heart activity were studied in 15 healthy pregnant women admitted for external cephalic version. The two-step infusion of terbutaline (5-10 micrograms/min) resulted in increases in maternal heart rate (p less than 0.001), cardiac output (p less than 0.001), systolic arterial pressure (p less than 0.001) and pulse pressure (p less than 0.001), while diastolic arterial pressure (p less than 0.001) and total peripheral vascular resistance (p less than 0.001) were reduced. Mean arterial pressure was unchanged after the infusion. Fetal heart activity assessed by cardiotocography showed a gradual increase in baseline fetal heart rate (p less than 0.01) and an increased percentage acceleration time (p less than 0.05). Fetal movements also increased during the infusion (p less than 0.05). The terbutaline infusion had a positive inotropic effect and produced decreased systemic vascular resistance in the pregnant woman, and placental transfer of the drug resulted in increased fetal heart activity. The potential influence of the drug-induced changes in maternal hemodynamics on utero-placental perfusion require further investigation. PMID- 2220344 TI - Acceleration of fetal maturation with intra-amniotic thyroxine in the presence of maternal malignancy. AB - Acceleration of fetal maturation with intra-amniotic administration of thyroxine was employed in eight patients in whom preterm delivery was necessary because of malignant disease of the mother. Thyroxine (200 mcg to 500 mcg) was given at weekly intervals starting at the 27th to 32nd week of gestation until the L-S ratio exceeded 2.0. The fetuses were delivered between the 29.4 and 34.0 week. None of the newborns suffered from respiratory distress syndrome, and three newborns were cared for in the regular nursery. Thyroxine-induced acceleration of fetal maturation and pre-term delivery permits earlier initiation of antineoplastic and radiation therapy without exposing the fetus to the hazards of maternal therapy and those of prematurity. PMID- 2220346 TI - Radical surgery compared with intracavitary cesium followed by radical surgery in cervical carcinoma stage IB. Analysis of patients less than or equal to 45 years of age with small tumors with regard to treatment results and ovarian preservation in the primary surgery group. AB - Forty-nine patients aged less than or equal to 45 years, with cervical carcinoma stage IB (less than or equal to 3 cm) were treated with either primary radical surgery (n = 26), or intracavitary irradiation followed by radical surgery (n = 23). With primary surgery, ovarian function had been preserved in 15 of the 25 patients, who were alive and well. Seven of the primary surgery patients were irradiated postoperatively and 2 others with a central recurrence were cured by irradiation. One other patient, who was not irradiated postoperatively, had an intestinal metastasis and died of the disease. If any of the adverse prognostic factors (as reported in the literature) had been considered as an indication for postoperative irradiation, 17 patients instead of 7 would have been irradiated after primary radical surgery. In the comparable group of 23 patients treated by intracavitary irradiation and radical surgery (and in 4 cases postoperative irradiation as well) there was no recurrence. There was no significant statistical difference between the treatment results in the cesium + surgery group and those who underwent primary radical surgery. Young patients with early cervical carcinoma without prognostic indicators for postoperative irradiation can benefit from primary radical surgery, because their ovarian function can be preserved. PMID- 2220348 TI - Familial cancer aggregation in cases of adenocarcinoma corporis uteri. AB - In a detailed prospective interview study, all newly diagnosed cases of adenocarcinoma corporis uteri at Malmo during a 2-year period (n = 51) were analysed with regard to the occurrence of tumors in first-degree relatives. The families of the proband's male consorts were used as controls. Sisters and mothers of probands had tumors (particularly of the corpus uteri or breast) more often than had controls. Colon and prostate cancer also figured in family histories of proband relatives, more often and with earlier age at onset than in controls. Nine patients (18%) either had additional concomitant malignancies, or had had such malignancies previously. Familial cancer predisposition was associated with poorly differentiated anaplastic cancer of the corpus uteri with poor prognosis. Three cases of familial cancer (CFS) observed at Malmo are also described, in which the probands presented with adenocarcinoma corporis uteri. The findings suggest that a hereditary, cancer predisposing factor (gene) is involved in a significant proportion of cancer corporis uteri, and that it is expressed in a heterogeneous tumor pattern, predominantly at sites sensitive to hormonal influences. PMID- 2220345 TI - Prevention of breast pain and milk secretion with bromocriptine after second trimester abortion. AB - Within 24 hours after abortion, 62 patients with a mean gestational age of 19 weeks, who had either induced (n = 50) or spontaneous (n = 12) abortions were randomly allocated to three groups: Group 1, bromocriptine 2.5 mg twice daily for 2 weeks; Group 2, placebo tablets 1 tablet twice daily for 2 weeks; Group 3, no treatment. Fifty-two patients completed the study (bromocriptine n = 18, placebo n = 18 and no treatment n = 16). Placebo had no apparent influence on breast symptoms. In both the placebo group and the untreated group, breast pain and milk secretion peaked on days 3 to 7, and milk secretion often continued for 3 weeks. Only 3/34 (9%) of untreated and placebo treated patients were free of breast symptoms. Compared with placebo, bromocriptine caused a significant reduction in the objective assessment score of breast tenderness (p less than 0.05) and milk secretion (p less than 0.01), in serum prolactin (PRL) (p less than 0.001) and in the subjective assessment score of breast pain (p less than 0.01) and milk secretion (p less than 0.01). Alleviation of breast pain and prevention of milk secretion appears to be indicated after second-trimester abortion, and treatment with bromocriptine is efficacious. PMID- 2220349 TI - Primary melanoma of the cervix uteri, an avis rara? A review of the literature. AB - A primary melanoma of the uterine cervix is presented. Diagnostic approaches and therapeutic procedures are discussed following a review of the literature. PMID- 2220351 TI - Fibroepithelial polyp of the ureter. A case history and discussion. AB - A 46-year-old woman had a 13 cm long benign fibroepithelial polyp arising in the right lower ureter and prolapsing through the urethral meatus. She also had uterine fibromyomata. She made an uneventful recovery after laparotomy with supravaginal amputation of the uterus and resection of a 1-cm segment of the ureter. Benign fibroepithelial polyps very rarely recur and may be treated with local resection. PMID- 2220350 TI - Ovarian metastatic carcinoma presenting as a primary cervical carcinoma. AB - A case of an ovarian carcinoma presenting as a primary cervical carcinoma is described. Although a rare event, this must be considered whenever the clinical or histological findings are unusual. The importance of careful histological review of all specimens in cases such as this is emphasized. PMID- 2220352 TI - Keratoprosthesis. I. Results obtained after implantation of 12 one-piece prostheses. A retrospective, follow-up study. AB - A total of 12 one-piece keratoprostheses were implanted in 6 eyes of 6 different patients with bilateral blinding, severe corneal disease with no possibility for a successful corneal transplantation. The prosthesis and the surgical procedure used are described. The short-term results were good, with 4 of the 6 patients obtaining a substantial visual improvement. In the remaining 2 patients preexisting pathology in the posterior segment of the eye was strongly suspected. However, the long-term complication rate was high, the chief problems being tissue necrosis around the prosthesis with eventual prosthesis loss and the development of retroprosthetic membranes. Repeated replacements of keratoprostheses extruded or removed because of complications were possible with restoration of the vision obtained after the first implantation. PMID- 2220354 TI - Granular corneal dystrophy Groenouw type I. Clinical aspects and treatment. AB - The paper describes the comparatively benign nature of granular corneal dystrophy Groenouw type I and the results of treatment of the disease. 71 patients with a classic clinical appearance comprised the largest pedigree in medical literature. The disorder was confined to the eyes only. Visual acuity was close to normal in children; the children had small, superficial, corneal opacities, often arranged in lines, and for the most part with a smooth exterior surface when examined with Javal keratometry. In adult patients visual acuity was around 0.5, the exterior surface uneven, the corneal opacities larger, and distributed superficially as well as deeper in the corneal stroma. In elderly patients visual acuity was between 0.5 and 0.1 and they all had additional cataract. Fourteen patients were treated with corneal grafting during the past 15 years and all grafts remained clear. PMID- 2220347 TI - Peripheral and ovarian venous concentrations of estradiol and progesterone in postmenopausal women with "non-endocrine" ovarian tumors. AB - Estradiol (E2) and progesterone (P4) levels in peripheral venous blood were measured in 45 postmenopausal (more than 5 years after menopause) women with ovarian neoplasms. The E2 and P4 concentrations in ovarian venous blood were also measured in 26 of these 45 patients. The steroid levels were compared with the values in 10 postmenopausal women without ovarian tumors. In peripheral venous blood, relatively high E2 concentrations were found in 24 of the 45 (53%) postmenopausal patients with ovarian tumors, and relatively high P4 concentrations were noted 15 of 45 (33%) of the patients. In ovarian venous blood, relatively high values of E2 were found in 18 of 26 (69%) of the postmenopausal patients, and relatively high values of P4 were noted in 11 of these 26 (42%). No differences in the E2 and P4 levels in peripheral and ovarian venous blood were noted between the patients with benign tumors and those with malignant tumors. These results suggest that some of the epithelial ovarian tumors in postmenopausal women have steroid-producing activity. PMID- 2220355 TI - The postnatal development of the oscillatory potentials of the electroretinogram. I. Basic characteristics. AB - The postnatal development of the oscillatory potentials (OPs) of the rat electroretinogram (ERG) was studied. The appearance and/or completion of the development of the individual oscillatory peaks differed from that of the a- and b-waves as well as from each other. The OPs appeared postnatally one to two days later than the a- and b-waves, respectively. The first oscillatory peak, O1, was present before the second, O2, which appeared before the later wavelets, O3, O4 and O5. The pattern of maturation of the oscillatory peaks in relatively more scotopic conditions differed from that in relatively more photopic ones. The summed amplitudes of the OPs attained adult size earlier (about two weeks) during relatively more scotopic conditions. The peak time of each oscillation gradually decreased with age. These findings show that the origin of the OPs is different from that of the a- and b-waves of the ERG and strongly indicate different origins of the earlier OPs from the later ones. Thirdly, the scotopic mechanism underlying the OPs seems to mature faster than the photopic system involved in the generation of the OPs. PMID- 2220353 TI - Keratoprosthesis. II. Results obtained after implantation of 27 dismountable two piece prostheses. A retrospective, follow-up study. AB - During the years 1974-1987 a total of 27 two-piece keratoprostheses were implanted in 25 eyes of 22 different patients with bilateral blinding anterior segment disease with no possibility for a successful corneal transplantation. The prosthesis design and the surgical procedures used are described. The healing in and fixation of the prostheses were initially good in all cases, but 9 prostheses were lost or removed because of complications during the postoperative period of observation. The prosthesis retention time was significantly longer than that earlier achieved by the use of a one-piece prosthesis. In 18 of 27 cases a visual acuity of 6/60 or better was obtained. Postoperative complications included necrosis of the tissues covering and supporting the prosthesis, infection around the prosthesis, overgrowth of the surrounding tissues and the development of dense retroprosthetic membranes. Despite the obvious risks, keratoprosthesis surgery in a small number of patients with severe corneal disease represents the only potential hope for a visual rehabilitation, and should therefore be considered. PMID- 2220356 TI - Occurrence of drusen, pigmentary changes and exudative changes in the macula with reference to age-related macular degeneration. An epidemiological study of 1000 aged individuals. AB - Macular changes in 60 to 80-year-old people i.e. drusen (DR), pigmentary changes (PC) and exudative changes (EXC) are assessed by fundoscopy in a random and age stratified population with 924 of the participants examined in both maculae (1848 eyes). DR, PC and EXC were found in 18.4%, 12.9% and 2.1% of all eyes with a rising frequency associated with increasing age. A separation was made between changes implying a visual acuity of 6/9 or less as criteria of age-related macular degeneration (AMD) and age related macular changes without visual impairment (AMCW). The occurrence of DR, PC and EXC from eyes with AMD showed an age related rise which was also found for DR, contrary to PC and EXC deriving from eyes with AMCW. The basic forms of AMD, atrophic and exudative, were represented in 78.6% and 21.4% of individuals or 80.9% and 19.1% of eyes with AMD. The predominant findings in AMD eyes were DR + PC in combination represented in 60.7% of atrophic and 66.8% of exudative AMD eyes, while in atrophic AMCW eyes DR as only finding was leading with 59.2%. It is concluded that in eyes with atrophic macular changes, DR, respectively PC as only finding involves no visual deterioration in 80.6%, respectively 72.6%, while DR + PC in combination, as well as the appearance of EXC, are found to be the most likely expression of AMD as long as a visual impairment of 6/9 or worse is included in the definition of AMD. PMID- 2220357 TI - Vitreous fluorophotometry in juvenile diabetics with and without retinopathy in relation to metabolic control: insulin antibodies and c-peptide levels. AB - Vitreous fluorophotometry was performed in 56 juvenile insulin-dependent diabetic patients aged 9-23 years (median: 16 years), diabetes duration 1-20 years (median: 8 years). Fundus photography showed mild background retinopathy in 5 patients, while 51 patients had no signs of retinopathy. Abnormal leakage into the posterior vitreous body was found in 4/5 patients with background retinopathy and in 24/51 with normal fundi. We found a significantly positive correlation between abnormal leakage and duration of diabetes and HbA1 with Kendall rank order correlation coefficients T = 0.21 (P = 0.01) and 0.19 (P = 0.02) resp. No significant correlation was found between leakage and age, actual blood glucose level or insulin antibodies expressed as insulin binding capacity of IgG, but a significantly negative correlation between abnormal leakage and low levels of fasting c-peptide/s T = 0.437 P less than 0.001. Kendall partial rank-order correlation analysis showed that c-peptide/s significantly explained the leakage when HbA1 or duration was kept constant. Duration could only explain leakage when HbA1 was fixed but not when c-peptide/s was kept constant. HbA1 could also explain leakage when duration or c-peptide was fixed. PMID- 2220358 TI - Coexistence of localized scotomata and neovascularizations in proliferative diabetic retinopathy. AB - Fifteen eyes of 15 patients with proliferative diabetic retinopathy within the central 60 degrees of the eye fundus were examined with computerized perimetry, and the visual field data were accurately correlated with the corresponding morphology as seen on fundus photographs and fluorescein angiograms. In 12 out of 13 eyes with neovascularizations outside the optic disc area an absolute scotoma could be correlated with a retinal area distal from the neocascularization, and in one case no scotoma was found in this area. The localized scotomata corresponded in 8 cases to non-perfusion areas as seen on fluorescein angiograms, whereas in 5 cases no pathological morphology was detected in these areas. Seven eyes which had neovascularizations at the optic disc showed the same pattern, but with visual field loss of more pronounced degree. Furthermore, other scotomata which not corresponded to any pathological fundus morphology occurred at approx. 30 degrees eccentricity in the visual field. The findings are discussed in relation to the current hypothesis about the initiation and development of neovascularizations in proliferative diabetic retinopathy. PMID- 2220360 TI - A longitudinal study of a population based sample of astigmatic children. II. The changeability of anisometropia. AB - The variability of anisometropi in a sample of 310 children with astigmatism at the age of 1 year was longitudinally studied during a 3-year period between 1 and 4 years of age. The prevalence of anisometropia of 1 D or more at each year level was rather stable. When individual cases were examined we found that between the first and the last test session 19 of the 33 children with anisometropia at the first test session had become non-anisometropic and were substituted with 14 new cases which were non-anisometropic at the age of 1 year. In general, less than half of the cases, at all levels of anisometropia, remained anisometropic throughout the whole test period. We also found that children with anisometropia persisting through the whole test period were at considerable risk, about one out of four, of developing amblyopia. There was no simple relationship, however, between anisometropia at a certain age level between 1 and 4 years and amblyopia and/or strabismus. Non-persisting anisometropia in an emmetropizing eye is in most cases a benign sign and not connected with an increased risk for developing amblyopia. PMID- 2220359 TI - A longitudinal study of a population based sample of astigmatic children. I. Refraction and amblyopia. AB - The refraction changes in 310 children with astigmatism greater than or equal to 1.0 D in at least one eye at one year of age were followed during a period of 3 years. At the age 4 years amblyopia was found in 23 children (7%). The refraction data of these children were compared to the rest of the sample. We found that an increasing astigmatism during the test period was associated with an increased risk to develop amblyopia. The majority of children (n = 280) showed a decrease of their astigmatism, whereas all cases with a marked amblyopia (V.A. less than 0.5) or binocular amblyopia, except one, had an increasing or unchanged astigmatism during the age period 1 to 4 years. Strabismus and oblique astigmatism at any time during the test period was also strongly related to amblyopia. The incidence of strabismus (1%) was unexpectedly low. The study also showed that independent of age there was no simple relationship between amblyopia and refraction errors measured at a single test session. The main conclusion of this study is that failure of emmetropization may play an important role in visual development. PMID- 2220361 TI - Retinal nerve fibre layer photography in glaucomatous and normal eyes. AB - The technique of retinal nerve fibre photography has been developed and tested in specialized centres and glaucoma clinics. The usefulness of a modified technique in clinical practice is the subject of this prospective study. Retinal nerve fibre photos from 41 patients with open-angle glaucoma and 40 normal patients were examined in a blind study, a total of 161 eyes. Photos from 5 eyes were of insufficient quality to allow evaluation. Nerve fibre loss was found in 36% of the normal eyes, 42% of glaucomatous eyes without visual field defects, and 87% of eyes with glaucomatous visual field defects. Sensitivity was 86% and specificity was 62% totally. In the younger patients aged less than 65 years both values were 82%. Photographic nerve fibre loss was found in 69% of normal eyes from patients aged more than 65 years, leading to a low specificity of 31% in this age group. Age related nerve fibre loss and clinically insignificant cataracts were the most obvious causes of non-glaucomatous nerve fibre loss. PMID- 2220362 TI - Screening for glaucoma with a non-mydriatic fundus camera. AB - 183 first-degree relatives of glaucoma patients were photographed by a technician with non-mydriatic fundus camera in order to study the suitability of wide angle black-and-white fundus photographs in screening for glaucoma. The success rate of photography was 92%. The optic disc and retinal nerve fiber layer abnormalities were evaluated from the photographs by an ophthalmologist. 31 subjects (17%) were referred to further ophthalmological examinations. We found 6 (3%) new glaucomas. In addition, in 6 patients (3%) retinal nerve fiber layer defect was the only abnormality, 5 subjects (3%) showed a hemorrhage and 2 eyes had collateral vessels as a sign of asymptomatic venous stasis change at the optic disc. Only 1 of the 6 (17%) patients with glaucoma would have been found with tonometry alone. The results of this study indicate that non-mydriatic retinal camera is a useful tool in screening for glaucoma. PMID- 2220365 TI - Role of aqueous and vitreous cultures in diagnosing infectious endophthalmitis in rabbits. AB - Staph.aureus endophthalmitis was induced in both eyes of 32 rabbits. Endophthalmitis developed in all the 64 eyes within 24-36 h. All vitreous cultures were positive while only 21 simultaneous aqueous cultures were positive. Thus, the importance of vitreous cultures in diagnosing bacterial endophthalmitis is emphasised. PMID- 2220363 TI - Optic disc haemorrhages preceding manifest glaucoma. AB - The Dalby population has been subjected to repeated glaucoma surveys in a deliberate effort to describe the early stages of glaucoma. A total of 28 haemorrhagic episodes were observed at 3819 examinations of persons not having manifest glaucoma. The prevalence of optic disc haemorrhages was dependent on age and residence. The mean IOP in eyes with optic disc haemorrhages was 17.0 mmHg. Only four out of 24 haemorrhages in eyes without pseudoexfoliations were associated with intraocular pressures over 20.5 mmHg. Of twelve cases followed more than six years two died and five developed manifest glaucoma. The period of latency between the detection of a haemorrhage and the development of a glaucomatous visual field defect was 2, 3, 5, 6, and 7 years, respectively. PMID- 2220366 TI - Immunohistochemical demonstration of epidermal growth factor in the lacrimal and submandibular glands of rats. AB - The extraorbital and intraorbital lacrimal glands, the Harderian glands, and the submandibular glands of five rats were excised after ethanol perfusion under general anesthesia. Indirect immunohistochemistry with antibodies specific to epidermal growth factor (EGF) was performed. EGF-like immunofluorescence (EGF-LI) was shown to be present both in the lacrimal glands (extra- and intraorbital) and in the submaxillary gland. In the lacrimal glands the specific immunoreaction appeared within the lumen of the acini and the cells of the tubular ducts close to the acini. Only faint EGF-LI was observed within the acinar cells. The submandibular glands showed intense EGF-LI only in the cells of the granular convoluted tubules. The Harderian gland did not show any EGF-LI. The results strongly support the idea that the lacrimal gland is a source of EGF in tear fluid (TF). Diseases of the lacrimal gland therefore may lead to decreased concentrations of EGF in tears. This may account in part for the pathophysiology of tear deficiency syndromes and may serve as the basis of a new rationale for the external application of EGF. PMID- 2220370 TI - Scleral dellen in strabismus surgery. AB - This communication highlights scleral dellen as an unusual complication of strabismus surgery in a 55-year-old hypertensive male. The clinical significance, differential diagnosis and management of this condition has been discussed. PMID- 2220371 TI - Workshop on current trends in growth related research. Proceedings of a meeting held in Haifa, Israel 24-27 October, 1989. PMID- 2220367 TI - Retinal nerve fiber layer in multiple sclerosis. AB - To evaluate the usefulness of the retinal nerve fiber layer (RNFL) appearance in estimation of optic nerve damage in MS, we examined 20 patients with definite MS and 20 normal control patients. Photographs of the RNFL in 80 eyes were classified as normal or abnormal by two examiners working independently. The results were very similar, even though the clinical data of which they were informed and their experience with RNFL-evaluation differed. We found RNFL defects in 80% of MS patients and in 73% of MS eyes. In the control group the values were 5% and 2.5%. Subclinical optic neuropathy in eyes without any history of optic neuritis was demonstrated by RNFL defects in 68%. We conclude, that in detecting clinical and subclinical optic neuropathy, RNFL-evaluation is to be recommended as the method of choice. PMID- 2220368 TI - The correction of ptosis with adjustable suture technique. AB - We discuss here the results of a simple technique for the correction of ptosis, performed by us as an alternative to other techniques. The basic principal of this technique is to suspend the ptotic upper eyelid to the frontalis muscle by 3/0 silk sutures passed above the tarsus using a peritoneal needle and to adjust the rima palpebrarum in the post-operative period. This method is simple and easy to perform with few complications. PMID- 2220374 TI - Endocrine basis for growth-promoting therapy. PMID- 2220372 TI - Growth hormone therapy: the ethical angle. PMID- 2220376 TI - The endocrinology of the pubertal growth spurt. PMID- 2220375 TI - The infancy-childhood growth spurt. AB - Early normal human linear growth is unstable and oscillates owing to an increase in growth rate between 6 and 12 months of age. This defines the onset of the infancy-childhood growth spurt (IC spurt). The onset is identical with the onset of the childhood component of the infancy-childhood-puberty growth model. The IC spurt is completed when the infancy component of this model has virtually ceased, at around 3 years of age. Additional observations suggest that its onset represents the age at which growth hormone (GH) begins to regulate growth significantly. The negative impact of late onset of the IC spurt on attained height is illustrated and discussed. A delayed spurt is observed in 30-50% of children with growth-related disorders and of infants living in a poor area of a developing country. The IC spurt is absent in children with GH deficiency who receive no hormonal therapy. PMID- 2220378 TI - Actions of growth hormone on adipose tissue: possible involvement of autocrine or paracrine factors. PMID- 2220379 TI - Cartilage as a target tissue for growth hormone and insulin-like growth factor I. PMID- 2220377 TI - The determinants of catch-up growth. PMID- 2220380 TI - Effects of growth hormone on body composition and metabolism. PMID- 2220381 TI - Growth hormone binding proteins in plasma--an update. PMID- 2220364 TI - Intraocular levels of cefuroxime in uninflamed rabbit eyes. AB - Intraocular levels of cefuroxime following subconjunctival, intravitreal and combined intravitreal and intravenous administration were determined in uninflamed rabbit eyes. Intraocular levels of the antibiotic were assayed by a biological method. Penetration of cefuroxime into the vitreous following subconjunctival administration was poor. Subconjunctival administration produced higher levels of cefuroxime in the aqueous when compared to parenteral administration alone. Higher levels of cefuroxime were achieved both in the aqueous and in the vitreous after an intravitreal injection. Intravitreal injection of 100 and 1000 micrograms cefuroxime produced intravitreal levels close to the minimum inhibitory concentration (MIC) for most ocular pathogens up to 24 h after drug administration. Intravenous supplementation did neither enhance the intraocular levels nor did it delay the clearance of the intravitreally injected antibiotic. Mild histopathological changes were seen with equal frequency both in the control and the test eyes and are attributed to the sampling techniques. Electroretinography (ERG) showed no definite changes suggestive of retinal toxicity up to 55 days after intravitreal administration. PMID- 2220373 TI - Fetal growth in late gestation--a constrained pattern of growth. PMID- 2220382 TI - Regulation of growth hormone receptor turnover by growth hormone. PMID- 2220384 TI - Treatment with human growth hormone: who, how, when and why? PMID- 2220387 TI - Is there an auxological basis for growth-promoting treatment with human growth hormone in short children? PMID- 2220386 TI - Gonadotrophin-releasing hormone agonist treatment of central precocious puberty: an analysis of growth data in a developmental context. AB - Growth and skeletal maturation was assessed in 83 girls with central precocious puberty (CPP) during pituitary-gonadal suppression induced by treatment with a gonadotrophin-releasing hormone agonist (GnRHa). The mean pretreatment chronological age (CA) was 6.3 years and the mean bone age (BA) was 10.6 years. During the suppression of gonadal sex steroid secretion, mean height velocity (HV) decreased from a pretreatment value of 10.8 cm/year to 5.9 (year 1, n = 83), 4.9 (year 2, n = 72), 4.2 (year 3, n = 45), and 4.4 (year 4, n = 23) cm/year. During each interval, there was a negative correlation between HV and the pretreatment BA. In addition, the rate of skeletal maturation was reduced during GnRHa treatment (delta BA/delta CA = 0.6 +/- 0.1 over 3 years, n = 45). The rate of skeletal maturation during therapy was also negatively correlated with pretreatment BA. Predicted adult stature, based upon zeta-scores of height for BA, increased significantly and progressively during therapy but the changes in height SDS for BA varied significantly. Since HV, delta BA/delta CA, and the change in height SDS for BA (delta HT SDS for BA) during pituitary-gonadal suppression all correlated with the initial degree of skeletal maturation, the effect of GnRHa therapy on final adult height in children with CPP will be best understood if growth data are assessed within a developmental framework. PMID- 2220388 TI - Biosynthetic human growth hormone in the treatment of growth hormone deficiency. AB - A total of 309 previously untreated children with growth hormone deficiency (GHD) (219 boys, 90 girls; mean age 8.4 +/- 3.9 years, range 1.5-19 years) were treated for up to 3 years in an ongoing trial designed to examine the long-term efficacy and safety of biosynthetic somatropin (rhGH). The children were treated with rhGH, 0.06 mg/kg (0.16 IU/kg) three times weekly. In the prepubertal children, the mean height velocity increased during the first year from 3.8 +/- 1.8 cm/year to 8.9 +/- 2.2 cm/year (n = 188). During the second and third years, their height velocities were 7.1 +/- 1.1 (n = 147) and 6.3 +/- 1.2 cm/year (n = 64), respectively. The height velocity SDS increased from -2.5 +/- 1.9 before treatment to 3.1 +/- 2.6 during the first year of treatment in the prepubertal children. The mean pretreatment height velocity in those with idiopathic GHD (3.8 +/- 1.6 cm/year) did not differ from that in children with organic GHD (3.8 +/- 2.3 cm/year). In addition, the height velocities during the first year of therapy did not differ significantly with respect to the aetiology of GHD. For the children who entered puberty during the study, the mean height velocity increased from 3.0 +/- 1.7 cm/year before treatment to 8.4 +/- 2.3 cm/year during the first year of rhGH therapy. In the first year, the height velocity of children with a bone age of less than 5 years (9.4 +/- 2.3 cm/year) was significantly greater than that in children with a bone age of 5-10 years (8.4 +/- 1.8 cm/year) or greater than 10 years (7.8 +/- 2.2 cm/year: p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220383 TI - Conclusions: a consensus statement on growth hormone therapy. PMID- 2220369 TI - Central vein thrombosis and topical dipivalyl epinephrine. AB - A report is given on an 83-year-old female who acquired central vein thrombosis in her seeing eye one day after having started topical medication with dipivalyl epinephrine for advanced glaucoma discovered in the other eye. From present knowledge about the effects of adrenergic eye drops on ocular blood circulation, it is difficult to suggest an association between the two events, which may be coincidental only. PMID- 2220385 TI - Neuroactive drugs in growth disorders. PMID- 2220389 TI - Effects of insulin-like growth factor I in man. AB - A 6-day period of subcutaneous infusion with recombinant human insulin-like growth factor I in three healthy male volunteers resulted in an increase in the ratio of insulin to C-peptide levels and significant decreases in triglyceride levels and the ratio of total to high density lipoprotein-cholesterol in serum. Increased renal plasma flow and glomerular filtration rates were also observed. PMID- 2220391 TI - Insulin-like growth factor II effects mediated through insulin-like growth factor II receptors. AB - Insulin-like growth factor II (IGF-II) resembles the homologous peptide insulin like growth factor I (IGF-I) in that it stimulates cellular growth in vitro. This effect is generally believed to be mediated through IGF type 1 receptors; the role of the IGF type 2 receptor remains, as yet, unknown. IGF-II has been shown to stimulate clonal expansion in cells from the human erythroleukaemia cell line K562, which displays binding of IGF-II and insulin but not IGF-I. This IGF-II effect was dose-dependent and correlated to the amount of specific binding; IGF-I did not stimulate growth. A similar effect on clonal growth was observed in the human T-cell line Jurkat. Furthermore, IGF-II was found to stimulate the cytotoxic activity of natural killer cells (as does interleukin 2). This effect was not inhibited by addition of IGF binding protein 1. Thus, it can be concluded that IGF-II, besides demonstrating standard IGF properties, exhibits unique biological effects in certain cells. PMID- 2220393 TI - Growth factors and the developmental neurobiology of the hypothalamus. PMID- 2220392 TI - Growth hormone-releasing hormone: structure, gene expression and molecular heterogeneity. PMID- 2220390 TI - Anabolic and tissue repair functions of recombinant insulin-like growth factor I. AB - Recombinant human insulin-like growth factor I (rhIGF-I) has been produced in yeast and purified using conventional biochemical techniques. It has been shown to have receptor-binding properties and in vitro growth-promoting activities comparable to those of plasma-derived IGF-I. The anabolic actions of IGF-I can be studied using both systemic and local administration in vivo. The growth promoting activity and systemic anabolic actions of recombinant IGF-I were studied in mutant dwarf rats. IGF-I was infused intravenously for 9 days and resulted in a significant gain in body weight and significant bone growth, though the effects were not as great as those observed with human growth hormone (hGH). IGF-I also had selective effects on specific organs which were not observed in hGH-treated animals. The results indicate that the growth-promoting effects of IGF-I show a different pattern compared to hGH. The effects of local administration of recombinant IGF-I on tissue regeneration and maintenance were also studied in hypophysectomized and normal rats. After hypophysectomy, the regeneration processes were impaired when both peripheral nerve regeneration and incision wound healing were considered. The results indicate that local administration could have significant effects on regeneration of, for example, peripheral nerves. PMID- 2220394 TI - Hashimoto's thyroiditis as a risk factor of thyroid lymphoma. AB - Hashimoto's thyroiditis (struma lymphomatosa), first described by Hashimoto in 1912, is an autoimmune inflammation of the thyroid commonly affecting middle-aged women. Histologic features of Hashimoto's thyroiditis (HT) include diffuse infiltration of lymphoid cells usually with formation of lymphoid follicles, varying degrees of fibrosis, oxyphilic change or squamous metaplasia in the epithelial cells. When the presence of focal lymphocytic infiltration is assumed to be an adequate criterion for diagnosis of autoimmune thyroiditis, the incidence appears to be as high as 16-23% in elderly females. An etiologically important role of HT in the development of thyroid lymphoma had been postulated, and recently, this was confirmed by epidemiological studies. In this article, a brief review of HT is given, together with results of our studies on thyroid lymphoma, and a discussion in the light of the pertinent literature. Immunologic and immunohistologic studies revealed that all of the thyroid lymphomas were of the B-cell type. Malignant lymphomas developing in patients with other autoimmune diseases such as Sjogren syndrome and rheumatoid arthritis have also been reported to be B-cell derived. Therefore it is suggested that immune deficiency is a causal factor for B-cell lymphoma. PMID- 2220396 TI - Gastric and intestinal phenotypic expression of human stomach cancers as revealed by pepsinogen immunohistochemistry and mucin histochemistry. AB - Gastric and intestinal phenotypic expression in 223 surgically obtained primary gastric cancers and their histogenetic relationship to intestinal metaplasia in the surrounding gastric mucosa were studied by mucin histochemistry and pepsinogen (Pg) immunohistochemistry. Histochemical differentiation of mucins (paradoxical concanavalin A, the galactose oxidase-Schiff sequence and sialidase galactose oxidase-Schiff) and immunohistochemical staining of Pgs I and II, allowed differentiation of gastric cancer cells from different histological categories into gastric elements including mucous neck cells, pyloric gland cells and surface mucous cells or intestinal elements including goblet cell and intestinal absorptive cell types. Of 122 papillary and tubular adenocarcinomas, 33 (27.1%) consisted mainly of gastric-type cells and 42 (34.4%) predominantly of intestinal-type cells. The remainder (38.5%) consisted of mixtures of gastric- and intestinal-type cells. Of 101 poorly differentiated adenocarcinomas, signet ring cell carcinomas and mucinous adenocarcinomas, 59 (58.4%) consisted mainly of gastric-type cells and 20 (19.8%) mainly of intestinal-type cells. Seven out of 35 papillary and tubular adenocarcinomas consisting mainly of gastric-type cancer cells were surrounded by mucosa with intestinal metaplasia. Conversely, 10 out of 40 papillary and tubular adenocarcinomas consisting mainly of intestinal-type cancer cells were observed in nonmetaplastic gastric mucosa. Thus no relationship as regards intestinal phenotypic expression was found between gastric cancers and surrounding gastric mucosa. PMID- 2220395 TI - Immune complex-induced disseminated intravascular coagulation (DIC). An experimental study. AB - Disseminated intravascular coagulation (DIC) was induced in rabbits by administration of antibody and antigen. The rabbits were sensitized passively by i.v. injection of antiferritin antiserum and challenged simultaneously by an i.p. inoculation of ferritin. After the challenge, circulating white blood cells, platelets and plasma fibrinogen levels showed an early fall, reaching minimum values at 3, 10 and 6 h, respectively. Fibrin thrombi appeared first at 2 h, reached a maximum at 5-7 h, and had mostly disappeared by 24 h. Formation of fibrin thrombi was frequent in the lung, liver, kidney and spleen. Early morphological changes included neutrophilic infiltration and accumulation of platelets in capillaries. Ferritin-antiferritin complexes were noted among fibrin thrombi or phagocytized by reticuloendothelial cells and neutrophils. The capacity of Kupffer cells to remove circulating immune complexes was saturated transiently; at this time fibrin thrombosis in various organs was most widespread and severe. It seems likely that formation of antigen-antibody complexes in the microcirculation initiates activation of platelets and neutrophils with subsequent release of mediators responsible for triggering DIC. Activation of complement was another possible factor inducing the reaction. In addition, blockade of the reticuloendothelial system promotes the progression of DIC. It is considered that the methods described constitute a useful model for further elucidation of immune complex-induced DIC. PMID- 2220397 TI - Immunohistochemical and gross dissection studies of annular pancreas. AB - Three cases of annular pancreas were studied immunohistochemically on an embryological basis in relation to the duct system. Annular pancreatic tissue was characterized by abundant, irregularly shaped islets with a very high proportion of pancreatic polypeptide (PP) cells, similar to those in the postero-inferior part of the pancreatic head of controls. This PP-rich area fused with PP-poor areas in both the anterior and posterior portions, resulting in encirclement of the duodenum except for a few PP-poor areas. The pancreatic duct of the annular tissue passed from the anterior portion to the lateral and posterior portions, finally joining with the main pancreatic duct. No connection was present between the duct of the anterior portion and the main pancreatic duct. Therefore, the annular pancreatic tissue was revealed to arise from the ventral primordium, supporting Lecco's theory that the free end of the ventral anlage is fixed. PMID- 2220398 TI - Expression of blood group antigens and lectin binding in adenocarcinomas of the endometrium. AB - To investigate cytoplasmic alterations in cancers of the endometrium, monoclonal antibodies against H, A and B blood group substances and related lectins such as Ulex europaeus agglutinin 1 (UEA-1), Lotus tetragonolobus agglutinin (LTA), and Griffonia simplicifolia 1 (GS1-A4, -B4) were applied to 42 cases of endometrial adenocarcinoma (EAC) and 11 adenomyoses. The control specimens consisted of normal endometria with leiomyoma or adenomyosis from patients of known blood group type. The brightest and most consistent staining was obtained with GS1-A4, showing 98% positivity in EAC in contrast to 18% in normal endometria. In contrast, expression of A antigen was seen in only 24% of EAC and in 13% of normal endometria, UEA-1 binding was seen in 81% of EAC and in 10% of normal endometria, whereas H antigen was seen in 60% of EAC and 0% of normal endometria. In adenocarcinomas, staining was seen not only along the luminal border of glands but also in the cytoplasm and the lateral or basal cell membranes, whereas in the normal endometrium staining was mostly along the luminal border. Thus, a difference in the positivity and localization of glycoconjugates was observed in neoplastic and non-neoplastic endometrium. PMID- 2220399 TI - Biclonality of composite B- and T-cell lymphomas. A case report. AB - Most composite lymphomas which are composed morphologically of two different tumor cell types are considered to represent different morphological expressions of a single clone. However, in recent years, composite B- and T-cell lymphomas and biclonality of B-cell lymphoma have been reported. We experienced a case of composite lymphoma which initially developed as cutaneous lymphoma composed of lymphoplasmacytes associated with large clear cells. It was confirmed that the tumor cells of these two systems were biclonal on the basis of surface markers and DNA rearrangements, i.e. B cells of the IgG kappa type, showing IgH and kappa chain DNA rearrangement, and T-cells with CD4 surface marker, showing rearrangement of the T-cell receptor beta chain gene. This case showed a predominant B-cell pattern at the initial stage, and terminated in T-cell lymphoma, as revealed at autopsy. Therefore we considered this case to be a unique composite lymphoma showing biclonality of both B- and T-cell systems, providing a number of suggestions for future study of malignant lymphoma. PMID- 2220400 TI - Characterization of myxoid substance of human aortic sarcoma. AB - An autopsy case of aortic sarcoma which was located in the intima of the abdominal aorta and characterized by abundant extracellular myxoid substances was examined. Histological, immunohistochemical and ultrastructural studies revealed no characteristics suggestive of endothelial, leiomyogenic or histiocytic differentiation. Histochemical and biochemical analyses revealed that the myxoid substances were glycosaminoglycans (GAGs) consisting of hyaluronic acid (85% of the total GAG) and chondroitin sulfate proteoglycan (15% of the total GAG). Neither heparan sulfate proteoglycan nor dermatan sulfate proteoglycan was detected. In the aorta, GAGs are synthesized mainly by arterial smooth muscle cells and endothelial cells. Among these cells, the arterial smooth muscle cell is the principal cell type that synthesizes aortic GAGs, predominantly chondroitin sulfate proteoglycan, whereas the endothelial cell synthesizes small amounts of GAGs, predominantly heparan sulfate proteoglycan. Therefore, the results of this study suggest that the tumor cells of the present case have a property similar to arterial smooth muscle cells in terms of GAG synthesis, and that the tumor originated most probably from arterial smooth muscle cells. PMID- 2220401 TI - Giant cell fibroblastoma. A case report. AB - A case of giant cell fibroblastoma occurring in the knee of a 16-month-old girl is reported. The ill-defined subcutaneous tumor measuring 2 x 2 cm was composed of diffusely proliferating spindle-shaped tumor cells with scattered, atypical multinucleated giant cells in a myxoid or collagenous background and irregularly branching sinusoid-like tissue spaces. In addition to floret-type giant cells, a few osteoclast-like giant cells were present in a cellular area where tumor cells were focally arranged in a storiform pattern. Immunohistochemically, the tumor cells gave positive reactions for only vimentin and actin. In spite of the high recurrence rate of this type of tumor, the course of the patient after excision of the tumor has been uneventful. It is important to distinguish this rare, peculiar fibrous tumor from other soft tissue tumors including some sarcomas. PMID- 2220402 TI - Role of fluid volume retention in angiotensin II salt-dependent hypertension. PMID- 2220404 TI - Role of renal nerves in volume homeostasis. PMID- 2220403 TI - Renal function curves and control of body fluids and arterial pressure. AB - The purpose of this paper has been to emphasize the extreme importance of the renal function curve in determining the long-term level of arterial pressure. The reason for this importance is that the renal-body fluid-pressure control system exhibits the phenomenon of "infinite feedback gain". This is, the arterial pressure will stabilize only when the intake and output of water and salt becomes exactly equal, and this occurs at only one very exact pressure level for any given renal function curve and given salt intake level. This renal mechanism for controlling the body fluids and simultaneously controlling the arterial pressure, because of its infinite feedback gain capability for controlling arterial pressure, requires that other pressure control mechanisms must interact with this mechanism either to alter the renal function curve or to make the animal change its intake of salt and water if the other pressure mechanisms are to have any effect on the long-term arterial pressure level. Therefore, in virtually any analysis of long-term arterial pressure regulation, the renal function curve or its mathematical equivalent plays a central role. PMID- 2220407 TI - The natriuretic effects of AVP and dDAVP: a lithium clearance study in conscious rats. PMID- 2220406 TI - Different effects of short and longer-term arginine vasopressin (AVP) administration on sodium excretion in Brattleboro rats. PMID- 2220405 TI - Quantitative aspects of renal actions of vasopressin. PMID- 2220408 TI - Role of blood pressure in the control of renin release. PMID- 2220409 TI - Role of the renin-angiotensin system in control of sodium excretion and arterial pressure. AB - The RAS is part of an extremely powerful feedback system for long-term control of arterial pressure and volume homeostasis as illustrated in Figure 4. Disturbances that tend to lower blood pressure such as heart failure, cirrhosis, and peripheral vasodilation, cause sodium and water retention until blood pressure returns to normal due in large part to the combined actions of ANGII and reduced renal perfusion pressure. In response to disturbances such as high sodium intake, suppression of ANGII greatly amplifies the effectiveness of the basic pressure natriuresis and diuresis mechanism, thereby preventing large increases in body fluid volumes and blood pressure. In circumstances in which the RAS is inappropriately activated, the sodium-water retaining effects of ANGII necessitate increased blood pressure to maintain sodium and water balance via pressure natriuresis. The sodium retaining actions of the RAS are mediated by intrarenal as well as extrarenal mechanisms. The intrarenal actions of ANGII include a direct effect on tubular sodium transport as well as a potent constrictor action on efferent arterioles which increases tubular reabsorption by altering peritubular capillary physical forces. The constrictor action of ANGII on efferent arterioles also plays an important role in stabilizing GFR and therefore in preventing fluctuations in excretion of metabolic waste products that depend upon a high GFR for excretion. ANGII is known to stimulate proximal reabsorption, but the effects on more distal tubular segments have not been completely elucidated. The primary extra-known to stimulate proximal reabsorption, but the effects on more distal tubular segments have not been completely elucidated. The primary extra-renal effect of ANGII which influences sodium excretion is stimulation of aldosterone secretion. Current evidence, however, suggests that the various intrarenal actions of ANGII are quantitatively more important in causing sodium retention than those mediated by changes in aldosterone secretion. However, the combined intrarenal and extrarenal actions of ANGII on sodium reabsorption provide the body with one of its most potent feedback systems for long-term regulation of body fluid volumes and arterial pressure. PMID- 2220410 TI - Contribution of the tubuloglomerular feedback mechanism to sodium homeostasis and interaction with the renin-angiotensin system. PMID- 2220411 TI - Intrarenal control of GFR, with special reference to proximal reabsorption. PMID- 2220412 TI - Psychosocial function before and after gastric banding surgery for morbid obesity. A prospective psychiatric study. AB - The objective of this study was to measure psychosocial functioning in morbid obese patients before and after horizontal gastric banding surgery, and to analyse the relations between the changes in psychosocial functioning and preoperative variables and degree of weight loss. METHODS: One hundred and three patients undergoing horizontal gastric banding surgery from 1982-85 were personally interviewed and rated by the author on DSM-III axis 1, 2 and 5, the CPRS, demographic data and precoded clinical scales. The interviews and ratings were completed in the last week before the operation. In addition the patients completed questionnaires concerning psychic symptoms (SCL-90) and quality of life. Twenty-five patients also completed the questionnaires six months before the operation. The patients were followed up after one and three years. RESULTS: There were 66 women and 24 men with a mean age of 35.4 years. Their mean preoperative weight was 121.8 kg corresponding to a Broca Index of 1.72 and a Body Mass Index of 41.5. They had a mean SCL-90/GSI score of 0.99. Fourty-one percent got a diagnosis on DSM-III axis 1 and 22% a diagnosis on axis 2. Thirty seven percent had made at least one contact with health services before the operation due to psychiatric problems. There were no strong relations between the relative preoperative weight and any other preoperative variable. The follow-up rate was 93%. The patients had a mean weight loss of 34.9 kg after one year and 31.5 kg three years after the operation. On group level the course and outcome of psychosocial functioning was a beneficial one. These changes were highly statistically significant and evident after one year, with only slight differences to the three years follow-up. The degree of weight loss explained a modest but statistically significant part of the variance in most of the psychosocial outcome variables when the preoperative level of the variable and the preoperative weight were controlled for. The degree of psychiatric contact in the follow-up period seemed to reflect another dimension. It was not related to the changes in the other psychosocial outcome variables, nor to the degree of weight loss, but was highly correlated to the degree of preoperative psychiatric contact. A group of patients with negative psychosocial outcome was identified. This group was characterized by a higher frequency of preoperative psychiatric help-seeking, than the rest of the patients. This pattern was most evident in a subgroup of 19% of the patients, who had a negative psychosocial reaction in spite of a sufficient weight loss.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2220413 TI - Whole blood luminol-enhanced chemiluminescence: statistical analysis of the responses of different subjects. AB - Whole blood luminol-enhanced chemiluminescence (CL) was studied using N-formyl methionyl-leucyl-phenylalanine (FMLP) or opsonized zymosan particles as stimuli. The peak and the integral responses of CL were recorded. In the FMLP-induced CL the initial activation (1-minute values) was also studied, because it coincides with the extracellular production of oxy radicals. Correction factors based on neutrophil count and on haemoglobin concentration were found to decrease dispersion and shape the distributions of the CL responses close to normal in a study of 50 healthy adults. One-minute values were significantly lower in women than in men but there were no significant differences for peak or integral values between sexes. Depressed reaction is in accordance with the previous findings that phagocytic oxy radical production is depressed in female plasma. Thus, our results suggest that 1-minute value is a variable more sensitive than peak or integral value of the CL response. PMID- 2220414 TI - Influence of gluten-derived fractions on chemiluminescence production by human neutrophils. AB - The effects of gliadin and glyc-gli on leukocyte chemiluminescence response were assessed in vitro. A dose-dependent increase in chemiluminescence response of neutrophils stimulated by zymosan was observed by using gliadin at concentrations ranging between 1 and 20 micrograms. By increasing glyc-gli concentration, a bimodal response was observed with an enhancement up to 50 micrograms/ml, followed by suppressive effects, which were again dose-dependent. The possible implications of these findings in human pathology are discussed. PMID- 2220415 TI - Chemiluminescence properties of human, canine and rat polymorphonuclear cells. AB - Human as well as canine and rat polymorphonuclear cells (PMN) were separated from whole blood by centrifugation. Two-step discontinuous Percoll gradients with distinct different densities were used. The chemiluminescence properties of the isolated PMN and of phagocytes in small quantities of whole blood were compared in luminol-enhanced assays after stimulation with various agents: non-opsonized zymosan (3.5 g/l), phorbol myristate acetate (PMA, 2.8 x 10(-6) mol/l), calcium ionophore A 23187 (10(-5) mol/l) and N-formyl-methionyl-leucyl-phenylalanine (FMLP, 3.5 x 10(-6) mol/l). The isolated cells of the three species responded to all of the various stimuli. Species-related sensitivity could be ordered: human greater than canine greater than rat. Response to the various agents in the human cells can be ranked: PMA greater than or equal to A 23187 greater than zymosan greater than FMLP; for the dog: A 23187 greater than PMA greater than zymosan greater than FMLP; and for the rat: zymosan greater than or equal to PMA greater than FMLP greater than or equal to A 23187. Time course and peak maximum response were different upon stimulation in the absence and presence of autologous plasma. Distinct soluble stimuli resulted in maximum responses below the baseline in the whole blood assays with canine (FMLP) and rat (FMLP, A 23187) phagocytes. PMID- 2220416 TI - Affinity purification of bacterial luciferase and NAD(P)H:FMN oxidoreductases by FMN-sepharose for analytical applications. AB - A modified purification method for bacterial luciferases and NAD(P)H:FMN oxidoreductases is described which uses FMN-Sepharose alone or coupled to DEAE ion exchange chromatography for the simultaneous purification of luciferase and the various oxidoreductases from Vibrio harveyi, a bright mutant of Vibrio harveyi, Vibrio fischeri, and Photobacterium phosphoreum. This purification method is compared with DEAE-Sepharose Cl 6B fractionations from these organisms. Both methods allow the separation of oxidoreductases specific for either NADH or NADPH. The use of FMN-Sepharose coupled to DEAE-Sepharose fractionation allows the isolation of highly purified enzymes. Lacking interfering factors, these are very suitable for various analytical applications based on bacterial bioluminescence enzymes. The partially purified enzymes from the affinity column have higher specific activities than those obtained using DEAE-Sepharose. PMID- 2220417 TI - Enhanced chemiluminescence in the measurement of proteins and haptens: evaluation of choriogonadotropin (hCG) and free thyroxin. AB - We evaluated the Amerlite system (Amersham, Bucks, UK) for hCG and FT4. The within-run imprecision (CV%) for hCG was 4.05 at 19.6 U/l (n = 10), 6.28 at 43.45 U/l (n = 10) and 4.62 at 298.57 U/l (n = 10). The between-run imprecision (five replicates for ten days) was 4.8%, 15% and 11%, respectively. The system was linear up to 200 U/l. A good correlation between Amerlite hCG and an IRMA assay (Becton Dickinson, r = 0.91), Delfia (Pharmacia, r = 0.91) and an automated ELISA assay on ES 600 (Boehringer, r = 0.92) was observed on 70 samples. Within-run imprecision for FT4 was 3.8% at 0.7 ng/dl (n = 10), 3.3% at 1 ng/dl (n = 10) and 4.32% at 5.15 ng/dl (n = 10), and between-run was 5.95%, 4.4% and 8.2%, respectively. The comparison with a commercial direct RIA (Becton Dickinson) showed good correlation (r = 0.90, n = 100 samples). The diagnostic value of the association of thyrotropin and FT4, in comparison with the traditional thyroid tests (T3, T4, thyrotropin, FT4, FT3) has been assessed in various thyroid diseases. PMID- 2220418 TI - Chemiluminescence (CL) in blood samples reflects leukocyte activation (LA) during anaphylactoid reactions in dogs. AB - Inflammation is accompanied by leukocyte activation (LA). We describe a simple ex vivo technique for studying LA that might help to find new LA inhibitors for the treatment of pathologic events related to LA. Arterial and venous blood samples obtained from six permanently catheterized beagle dogs -60, 0, +15 min and +23 h after i.v. challenge with C 48/80, and also blood samples from six normal beagles, were minimally diluted 1:2.5 with buffer. Total leukocyte counts (LC), and luminol amplified CL, induced by opsonized zymosan (C3-Z), were estimated. Blood samples from dogs elicited CL responses of almost 1/10 the magnitude of erythrocyte-free human leukocytes, whereas blood samples from rats reacted three orders of magnitude less. Obviously quenching of CL by accompanying erythrocytes in blood samples from dogs is not important, for CL correlated almost linearly with the CL in differently diluted samples. In arterial, but not in venous samples from catheterized dogs, absolute CL and LC, both were significantly depressed (p less than or equal to 0.05) 15 min after C 48/80 challenge. CL/10(6) leukocytes was augmented twofold. All leukocyte deviations returned to pre-values 23 h post-challenge. PMID- 2220419 TI - Chemiluminescence of irradiated animal blood plasma. AB - Spontaneous and induced chemiluminescence of rat blood plasma following irradiation of the animals with fast neurons was studied. Dynamics of the luminescence reflected the degree of radiation injury and an oscillatory response of blood chemiluminescent effect was observed. PMID- 2220420 TI - A new fluorescence enhancement solution for europium-based time-resolved fluoroimmunoassays. AB - A cationic detergent is proposed as suitable insulating agent for the preparation of a fluorescence enhancement solution useful for europium-based time-resolved fluoroimmunoassays. Luminescence from europium ions at concentration as low as 0.5 pmol/l can be detected in solution containing 1.6 mmol/l thenoyltrifluoroacetone, 110.5 mumol/l Adogen 464 and 0.1% Tween 20, in the presence of 0.5 mol/l NaCl. A competitive TR-FIA for rabbit IgG is described, showing that the new enhancement solution allows a sensitivity comparable to that of the high performance LKB Wallac DELFIA. PMID- 2220421 TI - Bioluminescence decay kinetics in the reaction of bacterial luciferase with different aldehydes. AB - At 22 degrees C the bioluminescence decay kinetics in the in vitro reaction catalysed by Vibrio harveyi luciferase in the presence of different aldehydes- nonanal, decanal, tridecanal and tetradecanal did not follow the simple exponential pattern and could be fitted to a two-exponential process. One more principal distinction from the first-order kinetics is the dependence of the parameters on aldehyde concentration. The complex bioluminescence decay kinetics are interpreted in terms of a scheme, where bacterial luciferase is able to perform multiple turnovers using different flavin species to produce light. The initial phase of the bioluminescent reaction appears to proceed mainly with fully reduced flavin as the substrate while the final one results from the involvement of flavin semiquinone in the catalytic cycle. PMID- 2220422 TI - [Endoscopic sphincterotomy in choledocholithiasis: analysis of an experience of 530 interventions]. AB - We report the experience of 530 consecutive cases of choledocolithiasis treated through Endoscopic Sphincterotomy (ES) between January 1980 and January 1988 (74% of total patients submitted to ES in the same period). 73% had more than 60 years and 47% more than 70 years. A slight majority (52%) had previous cholecystectomy (1/3 still with T-tube drainage) and the remaining had gallbladders insitu (lithiasic in 82%). Therapeutic goals (achieved drainage and complete stone removal) have been achieved in 95% of patients with a low immediate morbidity (9%) and mortality (1%). Delayed mortality, until 30th day (3%) includes 6 cases of obstructive cholangitis with sepsis, unaltered by emergent ES. Follow-up showed a 3% incidence of reintervention from restenosed ES. Patients with lithiasic gallbladder had a 33% cholecistectomy rate, mostly elective during first month post-ES. Our experience confirms ES as an efficient and safe routine treatment for choledocolithiasis. It should be the first choice in patients with previous cholecystectomy or alithiasic gallbladder and a largely applicable tool in those with associated gallbladder stones. Decision about post-ES cholecystectomy in these patients must be weighed on clinical grounds and according to surgical risk groups. PMID- 2220424 TI - [Treatment of anemia in patients with chronic kidney insufficiency in hemodialysis with erythropoietin]. AB - A group of 50 patients (26 men and 24 women, mean age 50 +/- 19 years and range 21 to 67) on chronic hemodialysis (HD) and with basal levels of hemoglobin (Hb) less than or equal to 8 g/dl was treated with recombinant human erythropoietin (r HuEpo) during 3 months. r-HuEpo was started at 50 U/kg I.V. 3 times a week, immediately after each session of HD, for 4 weeks, and this dose was increased in steps of 25 U/kg until a Hb level of 12 g/dl or a maximum dose of 100 U/kg were reached. Complete blood counts and biochemical profile were performed before the first dose of r-HuEpo and once weekly and monthly respectively during the period of treatment. In 8 patients the red-cell life span was studied with cromium 51 labelled erythrocytes just before and after treatment. One patient had a grand mal seizure and the r-HuEpo was discontinued. In 44 patients the mean hematocrit increased from 21.8% to 32.1% and in the other 5 there were no response because of iron deficiency. There were no changes in leucocytes and platelets counts and consistent decreases in iron and ferritin serum concentrations were observed despite oral supplementation of iron. In the 8 patients studied the shortened erythrocyte survival did not suffer any significant variation with r-HuEpo. Predialysis creatinine, urea and phosphorus blood levels increased significantly at 3th month of treatment but there was no increase in potassium. In 32.6% of previously normotensive and hypertensive patients an increase in blood pressure was founded. Thrombosis of arteriovenous fistulas and other severe clinical side effects were not observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220423 TI - [Preservation of the liver using a new solution of phosphate-buffered saccharose]. AB - The efficacy of the new phosphate-buffered sucrose solution (PBS), was compared with the conventional Euro-Collins (EC) and the lactated Ringer solution (LR), in its capacity to preserve the canine liver in cold storage. Three groups of 6 canine livers, each group in one of those solutions, were put in cold storage for 24 h at 4 degrees centigrade. At the end of this period the effect of warm hepatic reperfusion was studied in relationship with the following parameters: weight of the liver, bile excretion, hepatic biopsy, Na, K, Ca, P and some tests used to evaluate the hepatic function. The results obtained confirm, that PBS has an important impermeant effect over the hepatocyte, simulating that described recently by Lam et al to the kidney. Contrary to the EC and LR, the PBS inhibits hypothermic cell swelling, is more effective in the preservation of the liver histology, and has an opposed effect to the weight gain tendency induced by cold storage. During the period of warm reperfusion, high volumes of bile excretion and lesser levels of K depletion were observed in the PBS model. PBS is easy to prepare, and it is not expensive. For these reasons PBS could be an advantageous substitute of the EC in liver preservation. PMID- 2220425 TI - [Cryptococcosis. A study of 9 strains of Cryptococcus neoformans isolated from immunodeficient patients]. AB - Five strains of Cryptococcus neoformans isolated from the cerebro-spinal fluid and 4 from the blood of AIDS patients, were studied. Although morphologically identical, they differed in the auxanographic pattern. All strains were pathogenic for mice by intracerebral route. Six isolates were sensitive and the other three resistant to 5-fluorocytosine. All strains were sensitive to the other antifungal tested: nystatin, amphotericin B, clotrimazole, miconazole, econazole and ketoconazole. PMID- 2220427 TI - [Affinity constant in radioimmunoassay]. AB - Values for the affinity constant were determined, in three kits, for seric gastrin, following the Scatchard plot and Michaelis-Menten representation. The determination of the affinity constant, K, is of great value for it defines the antigen-antibody complex stability and it gives information about some aspects of the analysis system: sensitivity and antibody saturation. PMID- 2220426 TI - [Idiopathic proctocolitis. Follow-up (1-13 years) of 71 patients]. AB - Follow-up was possible in 71 of 74 patients with idiopathic proctocolitis diagnosed and/or assisted at the Department of Gastroenterology of the Centro Policinico de Almada, between 1973 and 1985. The aim of the present study was to verify the natural history of the disease and if there were statistically significant differences depending on the extension of the disease (proctitis versus colitis). Complications were present in 22 patients (31%): peri-anal (10%), local or intestinal (24%) and extra-intestinal (28%). Fifteen patients (21% of the cases) had hospital admission at least once, and 2 of them (3%) were submitted to surgery. No cases of cancer of the colon and rectum were detected and mortality was nil. Forty-one patients (58%) were assymptomatic at the last observation (45% with colitis and 75% with proctitis). There were statistically significant differences between the group of patients with ulcerative colitis and that of proctitis concerning the total number of complications (p less than 0.001), local complications (p less than 0.01), extra-intestinal complications (p less than 0.05), need for hospital admission (p less than 0.001) and absence of symptoms at the time of last observation (p less than 0.05), thus confirming a better prognosis of the disease when only the rectum is involved. PMID- 2220428 TI - [Evolution of clinical teaching at the Medical School of Lisbon (2)]. AB - Clinical teaching at Lisbon's Faculty of Medicine is analyzed in its two phases: 1. A period of stability and continuity of the institution (from 1911 to 1947) characterized by good rules in the selection of teachers: an impressive group of personalities (F. Gentil, Pulido Valente, Reynaldo dos Santos, Egas Moniz, A. Flores, Sobral Cid, Lopo de Carvalho, Gama Pinto, etc). At the same period a true University Hospital (of Santa Marta) provided clinical investigation (cerebral angiography and leucotomy, aortography and arteriography of the limbs, angiopneumography, endarterectomy) and the creation of new specialities (neurosurgery, vascular surgery, pneumology) (Act. Med. Port. 1990; 2: 109-114). 2. A period of instability due to a deleterious political intervention (from 1947 to the present day) responsible for the destruction of the structure and concept of a new teaching hospital (Hospital de Santa Maria). As a result of the socio political situation conflicting laws and vicious rules lead to an excess of non selected teachers and an alarming increase of students, patients and medical doctors A change from the present situation and a new concept of clinical teaching must be imagined. PMID- 2220429 TI - [Neoplastic hypercoagulability. Apropos of 2 cases with Trousseau syndrome]. AB - The authors describe two cases with venous thromboembolism and neoplasia (ovary and stomach), which also showed evidence of arterial thromboembolic phenomena- cerebrovascular disease in the 1st case and acute myocardial infarction in the 2nd case--favouring the existence of nonbacterial thrombotic endocarditis. This presentation of neoplastic hypercoagulability is frequently underrated in clinical practice. Pathogenesis, clinical manifestations, etiology, and therapeutics of these syndromes are discussed in relation to the presented cases. PMID- 2220431 TI - Placental haemangioma associated with acute fetal anemia in labour. AB - A case of pregnancy complicated by a placental hemangioma is presented. This was unassociated with any of the complications commonly coexistant with this tumor, and presented with fetal anemia due to a fetomaternal transfusion. PMID- 2220430 TI - [Intra-arterial occlusion of renal arteriovenous fistula using a detachable balloon]. AB - Several intra-arterial embolization techniques with polimerization substances, particles, thrombogenic coils and silicone and latex balloons have been used in the endovascular therapy of arteriovenous fistulas in different vascular territories. Using the Seldinger technique by femural route and with a coaxial system including a microcatheter with a latex Debrun type balloon, the authors describe the selective occlusion of an iatrogenic arteriovenous fistula of the left kidney. PMID- 2220432 TI - [Radiotherapy of malignant melanoma]. PMID- 2220433 TI - Function of dog's auditory cortex in tests involving auditory location cues and directional instrumental response. AB - Twenty one dogs, distributed into four groups, were trained pre-operatively in differentiation of auditory location or frequency cues. In each group instrumental responses, reinforced by food consisted in placing by the animal its right paw on the side levers. The first differentiation, go-left, go-right task with two location cues, required the animal to place its paw on the lever opposite to the source of the cue. The second differentiation task with the same location cues required placing the paw on the lever located close to the cue. The third task, involving 700 Hz vs. 1,000 Hz tone, required responding to one lever to the presentation of one tone and responding to the opposite lever to the presentation of the other. The last task was a symmetrically reinforced go, no-go differentiation with, again, auditory location cues: the animals were trained to place the paw on a lever to one location cue and to withhold this response to the other location cue. Bilateral ablation of the primary auditory cortex produced a considerable impairment of the performance of the two go-left, go-right tasks involving location cues. The go-left, go-right task employing frequency cues, and the symmetrically reinforced go, no-go task with location cues, were only slightly disturbed by this lesion. PMID- 2220435 TI - Electrical activity and feeding correlates of intracranial hypothalamic injection of GABA, muscimol and picrotoxin in the rats. AB - Assemblies of electrodes and a cannula were stereotaxically implanted in the ventromedial (VMH), lateral (LHA) and paraventricular (PVH) hypothalamic areas in male albino rats. Electrical activity of these regions was recorded electrographically before and following intracranial injection (ICI) of GABA, muscimol and picrotoxin. In another set of animals, food intake and water intake were also measured. The activity of the ventromedial hypothalamus changed from slow to fast after ICI of GABA and picrotoxin and fast to slow after muscimol. The activity of the lateral hypothalamus changed from slow to fast with ICI of muscimol and picrotoxin and from fast to slow with GABA, while that of the paraventricular hypothalamic nucleus changed from slow to fast with ICI GABA and fast to slow with muscimol and picrotoxin. ICI of GABA into VMH and LHA and muscimol in VMH, LHA and PVH caused a decrease in food intake. Water intake was also decreased after ICI of GABA in PVH and muscimol in LHA and PVH. On the opposite picrotoxin increased food intake in VMA and LHA and water intake in PVH. The possible interaction of GABAergic drugs with the areas of the brain controlling feeding and drinking is being discussed. PMID- 2220434 TI - Post-stress analgesia after lesions to the central nucleus of the amygdala in rats. AB - In two experiments the role of the central nucleus of the amygdala under two modes of foot-shock analgesia was studied in 39 male Moll-Wistar rats. In Experiment I a 4 min continuous foot-shock, dependent on neural mechanism was used as a stressor. Analgesia was produced by regularly intermitted 20 min of foot-shock action in Experiment II which evoke an opioid, humorally mediated mechanism. The results suggested that the central nucleus is involved only in the humoral regulation of the opioid form of analgesia. This finding fits well with the concept of limbic control of the anterior pituitary and the pituitary adrenocortical axis, and points to the role of the amygdaloid complex in processing of stressful stimuli. PMID- 2220436 TI - The perception of figure reversal as a function of contrast reversal exemplified with the Schroder staircase. AB - During spontaneous reversal of a reversible figure (Schroder staircase), subjects spent less time in perceiving line drawings white on black then black on white. Possibly the first stimulus makes a stronger three-dimensional impression. PMID- 2220437 TI - Structure of spinal cord locomotor strip in the cat. AB - The origin of spinal locomotor strip fibers was studied in the cat by means of electrical stimulation combined with horse-radish peroxidase transport technique. It was revealed that a corticospinal tract presumably formed the locomotor strip. Some reticulospinal and trigeminal tract fibers were also found. Descending catecholaminergic fibers do not pass through the investigated regions of dorsolateral funiculus; probably they are not a part of the spinal locomotor strip. PMID- 2220438 TI - [Minor neurological signs in obsessive-compulsive disorders]. AB - Present and classic observations allow us to relate the obsessive-compulsive disorder (OCD) with different structural and functional anomalies, disorders and neurological findings which let us elaborate etiopathogenic and therapeutic hypothesis. From this and from our experience in the study about soft neurologic signs (SNS) in psychiatry, we explored 20 patients with OCD (DSM-III), compared with 28 phobic disorders and 20 healthy controls, following a SNS protocol and picking up demographic and clinical variables. We besides administered intellectual efficiency exams (WAIS) and neuropsychological tests (Benton/Bender), blind to the SNS exploration. The OCD group showed a higher global incidence of SNS, and especially more alterations in movement's coordination in upper extremities and balance with a trend to show more anomalies in dominance-laterality. This higher incidence of SNS didn't correlate with age, familiar or personal psychiatric history, indicators of neuropsychological impairment and pharmacotherapy. Men with OCD showed more SNS than women did, and as men have higher schooling rates, we found a relationship between SNS and schooling. OCD group showed a trend to be more intelligent than healthy controls, reaching significant higher scores in verbal than in manipulative scales. This lower manipulative score could relate with SNS, suggesting a possible concordance or significant relation with neurobiologic hypothesis, but not supporting neuroevolutionary and organic impairment theories as OCD etiopathogenesis. PMID- 2220439 TI - [The distinctive quality of depressed mood. V: Its prevalence in depressive disorders]. AB - A prevalence of the 90% of "distinct quality" in depressed is detected using the Pathological Sadness Index. Its presence is non dependent of the presence or absence of life event and it is more frequent in melancholic subjects. The Pathological Sadness Index show a presence of "distinct quality" in 83% of cases without subjective experience of it. PMID- 2220441 TI - Asymptomatic ischemia: resolved and unresolved issues. PMID- 2220440 TI - [Description of patients diagnosed with "alcohol dependence syndrome" and "alcohol abuse" according to the C.I.E.-9a criteria of the W.H.O. at a psychiatric hospitalization service]. AB - The authors make an introduction where they describe several problems found in the alcoholic diseases researches. The most important of them are related to the "alcoholic case" concept. After this the authors report several epidemiological facts about the alcoholic diseases and disorders in Castilla-Leon and Madrid. Then a retrospective analysis of inpatients psychiatric records from the Psychiatry Department of Valladolid's University Hospital between 1980 to 1984 (N = 1.259) is made. 252 (20.01%) of them suffered an alcoholic disorders, following the I.C.D.-9th criteria psychoses alcoholic were 102 (8.10%) and they were excluded. However "Alcohol dependence" with 128 cases (10.17%) and "Alcohol Abuse Syndromes" with 22 cases (1.75%) were studied deeply, being 150 cases--120 males (80%) and 30 females (20%)--evaluated. Every diagnostic group was analysed in a distinct way through 41 epidemiological, clinical, diagnostic and medical care variables. These two groups and their differences and similarities between them are reported. The main profile is a male patient, 43 years old, married, urban life, blue collar worker, unskilled work, primary studies, bad economic level, marriage and working maladapted, clinical admitted through the Emergency Service, with an alcoholism 24 years old and intake of 234 grs. alcohol/day, with former treatment of minor tranquilizers (B.D.Z.) and at last is readmitted by alcoholic disease of disorder or a different psychiatric disease or disorders (I.C.D.-9.a or D.S.M.-III) in a 37.5% and 16.41% respectively. PMID- 2220442 TI - Ambulatory monitoring of left ventricular function: a new modality for assessing silent myocardial ischemia. PMID- 2220443 TI - The hidden entity of right ventricular ischemia. PMID- 2220444 TI - Significance of experimental models in assessing the link between myocardial ischemia and pain. PMID- 2220445 TI - Pain perception and endogenous pain modulation in angina pectoris. PMID- 2220447 TI - Variability of myocardial ischemia: implications for monitoring strategies. PMID- 2220446 TI - Silent ischemia during PTCA: its relationship with exercise-induced silent ischemia and the possible role for beta-endorphins. PMID- 2220448 TI - The prognosis of individuals with silent myocardial ischemia. PMID- 2220449 TI - Incidence, precursors and prognosis of unrecognized myocardial infarction. PMID- 2220450 TI - Risk stratification in unstable angina: screening for silent myocardial ischemia. PMID- 2220451 TI - Ischemia detected on ambulatory monitoring: has it prognostic implications? PMID- 2220452 TI - Scintigraphic evidence of silent myocardial ischemia in post-infarction patients: prognosis implications. PMID- 2220453 TI - Silent myocardial ischemia after coronary artery bypass graft surgery. PMID- 2220454 TI - Prognostic significance of silent myocardial ischemia by exercise testing. PMID- 2220455 TI - Coronary angioplasty in silent and painful myocardial ischemia. PMID- 2220456 TI - Silent myocardial ischemia after bypass surgery and percutaneous transluminal coronary angioplasty. PMID- 2220457 TI - Diabetes mellitus and silent myocardial ischemia. PMID- 2220458 TI - Silent myocardial ischemia in asymptomatic patients: should we screen? Should we treat? PMID- 2220460 TI - Ischemic preconditioning and myocardial stunning: related consequences of brief coronary occlusion and reperfusion? PMID- 2220459 TI - Significance and management of silent myocardial ischemia. PMID- 2220461 TI - Management strategies for high-risk patients with silent myocardial ischemia. PMID- 2220462 TI - Mechanisms of silent myocardial ischemia: implications for selection of optimal therapy. PMID- 2220463 TI - Silent myocardial ischemia: potential for clinical trial. PMID- 2220464 TI - Myocardial ischemia: pathogenic role of disturbed vasomotion and endothelial dysfunction in coronary atherosclerosis. PMID- 2220465 TI - Silent ischemia during mental stress: scintigraphic evidence and electrocardiographic patterns. PMID- 2220466 TI - Ambulatory monitoring and silent myocardial ischemia: have the basics been done? PMID- 2220467 TI - Myocardial effects of brief periods of ischemia followed by reperfusion. PMID- 2220468 TI - Methodological aspects of detecting patients with symptomatic and silent myocardial ischemia. PMID- 2220469 TI - Real-time digital monitoring: current capabilities and future role. PMID- 2220470 TI - Expression of a plant virus-coded transport function by different viral genomes. PMID- 2220471 TI - Structural and functional properties of plant reovirus genomes. PMID- 2220472 TI - Regulation of tobamovirus gene expression. PMID- 2220473 TI - Adverse drug reactions in neonatal intensive care units. PMID- 2220474 TI - Are pesticides immunotoxic? AB - So far there is little evidence that occupational or environmental exposure to pesticides has led to clinically significant immunosuppression, and hence to an increased risk of developing infection or cancer. In addition, the incidence of hypersensitivity reactions to pesticides is generally low. Experiments have been conducted in experimental models that indicate that certain pesticides are immunosuppressive to animals. The majority of these experiments, however, have used high (frankly toxic) doses of pesticides and immunosuppression has been monitored using in vivo or in vitro immune function tests, the results of which are difficult to interpret in terms of effects on health. One exception is tributyltin oxide which, in the rat, causes immune dysfunction at doses below those that cause general toxicity, and which compromises the ability of the animals to resist bacterial and parasitic infection. Predictive assessment of possible immunotoxicity induced by exposure to a pesticide should be structured within the current framework of acute, subacute and chronic testing procedures used for regulatory purposes. With the exception of predicting some hypersensitivity reactions (respiratory allergy and autoimmunity), which would require the development of novel specialized methods, indications of potential immunotoxicity can be obtained from standard haematological investigations and by evaluation of lymphoid organs and tissues such as the spleen, thymus, lymph nodes, and bone marrow. Pathological and histopathological examination of the lymphoid system is a mandatory requirement of nearly all subchronic testing guidelines for pesticides worldwide. The incorporation of specialized, and in particular in vitro, immune function tests into the routine toxicological assessment of a pesticide is not only time-consuming and potentially wasteful of animals, but is also scientifically unacceptable; the significance of changes in such tests must await further research on the reserve capacity of the immune system. PMID- 2220476 TI - The relation between immunology, nutrition and disease in elderly people. PMID- 2220475 TI - Amino acids and proteins in relation to the nutrition of elderly people. AB - In this short review some aspects of body protein and amino acid metabolism during ageing in human subjects have been explored. The picture that emerges is a progressive diminution of total body protein with ageing, due largely to a decline in the size of the skeletal muscle mass. These changes are accompanied by a shift in the overall pattern of whole body protein synthesis and breakdown, with muscle mass estimated to account for about 30% of whole body protein turnover in the young adult, as compared with a lower value of 20% or less in the elderly subject. The metabolic significance and possible functional implications of this alteration in the quantitative contribution by muscle to whole body amino acid and protein dynamics have been considered. The determination of requirements for individual essential amino acids and for total protein has been discussed, and it is evident that the data are limited and often contradictory. However, elderly individuals are more likely to be influenced by various biological, environmental and social factors, the effects of which would be generally to increase protein needs above those for younger adults. Thus, in practice, the protein needs of elderly people are probably higher than for the young. The decline in energy intake, together with its possible consequences for reduced dietary protein utilization, will also tend to increase the protein need of elderly subjects, compared with that for physically more active young adults. Until more data become available, it is recommended for food planning purposes that an appropriate protein allowance could be 12-14% of the total energy intake, for mixed protein sources characteristic of the diets of industrialized countries or the more affluent sectors of populations in developing countries. Energy intake should be at a level that meets the estimates proposed by FAO/WHO/UNU for older persons. Tentative recommendations are made herein that intakes of specific indispensable (essential) amino acids, per unit of protein need, should be similar to those for the young school-age child and they should be higher than those currently judged by international authorities (i.e. FAO/WHO/UNU) to be sufficient for maintenance of protein nutritional status in the adult. In view of (i) the increasing proportion of older individuals within technically advanced populations together with the need of this group for health care and (ii) the important role played by diet and food habits in health maintenance, and in the aetiology or progression of degenerative disease, it is vitally necessary to improve upon the current state of knowledge concerning protein and amino acid metabolism and nutrition during the later phases of our lives. PMID- 2220477 TI - Nutritional aspects of dementia, especially Alzheimer's disease. PMID- 2220478 TI - Trans-cultural aspects of nutrition in old age. PMID- 2220479 TI - Physiology of ageing: nutritional aspects. PMID- 2220480 TI - Postprandial hypotension in elderly people. PMID- 2220481 TI - Elderly patients' understanding of their drug therapy: the effect of cognitive function. AB - The relationship between cognitive function and knowledge about drug therapy and its risks was examined in 207 elderly patients attending a geriatric outpatient clinic. The patients' reports of their therapy were compared with those of their clinic doctor. Patient-doctor agreement on the number of drugs taken per patient fell with increasing age independently of change in cognitive function. However, knowledge about drugs was related to cognitive function. Many patients taking some of the potentially more dangerous drugs were ignorant of possible side effects of their treatment. Doctors need to be trained more effectively in communicating with elderly patients about their treatment and its risks. PMID- 2220482 TI - Changes in carotid artery compliance with age. AB - Doppler-shifted ultrasound was used to measure arterial compliance non-invasively in the internal and external carotid pathways of 270 male and 388 female asymptomatic volunteers aged 5 to 90 years. There was a significant decrease in the compliance of both arteries from 5 to 50 years of age (p less than 0.001), when it then levelled out. Arteries of women were more compliant than those of men at ages 35 to 60 years. PMID- 2220483 TI - Dementia and abnormal breathing during sleep. AB - We have examined a group of cognitively impaired elderly people who already showed some increase in indices of sleep-disordered breathing and applied standard criteria for dementia to them. This resulted in a subgroup of truly demented subjects who showed significantly more abnormal breathing during sleep than either normal subjects or those whose cognitive impairment may not have been due to a dementing illness. PMID- 2220484 TI - Affective flattening in elderly patients. AB - Forty-eight consecutive patients not taking dopamine antagonists and without Parkinson's disease referred to a psychogeriatric service with a diagnosis of psychiatric disorder were assessed for affective flattening using an objective rating scale. Nearly half (44%) exhibited significant affective flattening, which proved open to reliable assessment. Affective flattening is a useful sign of pathology. PMID- 2220485 TI - Predicting urodynamic dysfunction from clinical features in incontinent elderly women. AB - In a retrospective survey of 296 elderly women referred with urinary incontinence and in whom urodynamic studies were completed, multiple logistic regression was used to determine the optimal set of clinical features to predict the urodynamic dysfunction. Three formulae were obtained expressing the predicted probabilities (p) of the urodynamic dysfunctions as functions of the clinical variables. By choosing the cut-off values of p which gave equal weighting to sensitivity and specificity, we found that clinical features (symptoms, signs, residual volume) are helpful in diagnosing the presence of unstable detrusor and voiding dysfunction, but not incompetent urethra. PMID- 2220486 TI - Hypothesis: temperature recommendations for elderly people: are we wrong? AB - By concentrating housing recommendations purely on temperature, particularly of the living room, the medical profession may be doing a disservice to the elderly and may be causing increased numbers of cold-related deaths through attempting to reduce the far fewer cases of hypothermia. The best advice may be to avoid having one room significantly warmer than the rest of the house, to prewarm the bed and bedroom at night, to wear adequate clothing, eat adequate food, and take some exercise. PMID- 2220487 TI - Fallers, non-fallers and Poisson. PMID- 2220488 TI - [Interaction between corneal invasion of polymorphonuclear leukocytes and corneal epithelium]. AB - The interaction between corneal invasion of polymorphonuclear leukocytes (PMNs) and corneal epithelium was investigated following different types of corneal injury. Histological examination of centrally denuded corneas demonstrated that it took 18-24 hours for PMNs to infiltrate into the center of the denuded stroma, approximately synchronous with the reepithelialization. On the other hand, in the centrally denuded corneas immediately covered by glue to prevent the reepithelialization, the time required for the appearance of PMNs at the central portion of the corneas was more than 96 hours. Chemotactic activities of PMNs in the conditioned media of normal cornea, completely denuded cornea and reepithelializing cornea were examined using a Boyden chamber. The highest chemotactic activity was defected in the conditioned medium of the cornea with reepithelialization. These data suggest the possibility that the corneal epithelium, especially the re-covering epithelium, stimulates infiltration of the stroma by PMNs. PMID- 2220489 TI - [Effects of T cell subsets on mouse herpetic keratitis]. AB - Immune splenocytes were obtained from C3H/He mice, which had been inoculated with herpes simplex virus (HSV) type 1 by the corneal route 6 or 12 days previously, and restimulated by lipopolysaccharide-induced lymphoblasts infected with HSV. These cells were either not treated or treated with anti-L3T4 antibody plus complement/anti-Lyt-2 antibody plus complement, and were transferred to subconjunctiva of mice with HSV corneal infection. Adoptive transfer of non treated cells diminished corneal ulcers, when the splenocytes were transferred from mice inoculated 12 days previously. This effect was reduced by depletion of Lyt-2 bearing cells, but not reduced by depletion of L3T4 bearing cells. Adoptive transfer of splenocytes from mice inoculated 6 days previously did not diminish corneal++ ulcers. These findings demonstrate that HSV specific cytotoxic T lymphocytes (CTL) play an important role in the late phase of recovery from HSV corneal infection. PMID- 2220490 TI - [The ultrastructural changes in the corneal lens stroma of wound healing process following epikeratophakia in rabbits]. AB - We investigated the ultrastructural change of corneal lens+ stroma histologically following epikeratophakia in rabbits. Epikeratophakia was performed on rabbit corneas using cryolathed corneal lens+. At days 10, 16, 45, 63 and 90 after the operation, pachymetry was performed, and corneas were excised and analyzed histologically using an electron microscope. At days 16 to 63, collagen fibril density (CFD) in corneal lens+ stroma decreased 57 to 63% of that in the control cornea, but returned to 78% at day 90. The results of pachymetry revealed that postoperative increase of corneal thickness was greater than the expected value at days 10 and 16. However, after that the corneal thickness decreased gradually and became thinner than the expected value after 45 days postoperatively. At days 45 to 90, many activated keratocytes with dilated and well developed rough endoplasmic reticulum, suggestive of active collagen production, were observed in corneal lens+ stroma. Furthermore, at day 90, keratocytes with extended pseudopoidia that suggested phagocytic activity were also observed, especially in the subepithelial zone. These findings indicated that collagen fibrils in the corneal lens+ stroma were damaged under the influence of the cryolathing process and partially exfoliated postoperatively, however, collagen-producing activity increased gradually and the reconstruction of corneal lens+ stroma continued through day 90 after the operation. PMID- 2220491 TI - [A polyvinyl alcohol (PVA) hydrogel as a soft contact lens material]. AB - A transparent polyvinyl alcohol (PVA) hydrogel was prepared from a PVA solution in a mixed solvent consisting of water and a water miscible organic solvent by cooling. The physical properties were evaluated in comparison with commercially available soft contact lens materials, such as polyhydroxyethyl methacrylate (PHEMA) and copolymers of methyl methacrylate (MMA) and N-vinyl pyrrolidone (VP). The PVA hydrogel showed higher tensile strength and elongation at break than the other materials, while it had high water content and oxygen permeability the latter being comparable to those of PMMA/VP copolymers. The protein adsorption of the PVA hydrogel was much less than those of the other materials. The PVA hydrogel soft contact lenses were applied on rabbit eyes for 12 weeks. The influence on the cornea was studied by biomicroscopy, ultrasonic corneal pachymetry and histopathological examination. These examinations revealed no abnormal findings in the cornea. These results suggest that the PVA hydrogel may be promising as a new soft contact lens material. PMID- 2220492 TI - [Ocular symptoms in mitochondrial myopathy]. AB - The corneal endothelial cells in 6 cases of mitochondrial myopathies were examined by specular microscope, and electron microscopic studies of the cornea were made in one autopsy case. The cornea was clear and the thickness was within the normal range. The endothelial cell mean size was larger in 3 out of 10 eyes than among controls and the variance of endothelial cell size was larger in all of 10 eyes than among controls. The difference was found to be statistically significant. Electron microscopical findings of the cornea revealed mitochondrial abnormalities. Inclusions were observed in the stromal keratocyte. PMID- 2220493 TI - [Intravitreal drug delivery by microspheres of biodegradable polymers]. AB - We evaluated the efficacy of microspheres of biodegradable polymers as a slow releasing drug delivery system in the vitreous body. Microspheres containing 5-FU were prepared with polymers of poly-(lactic acid) or copolymers of glycolic acid and lactic acid. The release of the drug was studied in vitro. Poly-(lactic acid) microspheres released 5-FU for 7 days. The intravitreal kinetics of the microspheres was studied in rabbits in vivo. The microspheres disappeared from the vitreous cavity of normal eyes by 48 +/- 5 days after injection. Disappearance was accelerated from the vitreous cavity of vitrectomized rabbits (14 +/- 2 days, p less than 10(-6)). No abnormality was found on electroretinographic or histological examinations after microspheres injection. These results suggested that microspheres of biodegradable polymers could be useful as a potential drug delivery system for sustained drug release in the vitreous body. PMID- 2220494 TI - [The influence of the intraocular pressure on the visual field of low tension glaucoma]. AB - To study the effect of the intraocular pressure (IOP) on the visual field (VF) damage in low tension glaucoma (LTG), we compared the IOP and the VF damage in both eyes of 46 LTG patients. As an index of the VF damage, we used the mean deviation (MD) value calculated by the Humphry (30-2) STATPAC program, and for the IOP data, the mean of 24 hour IOP measurements (diurnal IOP) and the mean of the IOPs measured at each visit to our outpatient clinics (follow-up IOP). In 13 cases, the diurnal and the follow-up IOPs were 0.3 mmHg higher or more in the more damaged eye than those in the less damaged eye, and in 7 cases they were 0.3 mmHg higher or more in the less damaged eye than those in the more damaged eye. Between these two groups, no significant difference was seen in the value of MD, but the diurnal IOP and the follow-up IOP was significantly higher in the former than in the latter group. By discrimination analysis, the two groups were distinguished at the diurnal IOP of 14.1 mmHg (hit rate 77.6%) and the follow-up IOP of 15.0 mmHg (74.2%). An analysis using the whole 46 LTG cases yielded the following results: when the diurnal or follow-up IOP of the more damaged eye was higher than the above determined level, the IOP in the more damaged eye was significantly higher than that in the contralateral less damaged eye.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220495 TI - [Autoregulation of macular capillary blood flow evaluated by the blue field entoptic phenomenon]. AB - Autoregulation of the macular capillary blood flow was investigated using a blue field entoptoscope and OCVM suction cup system. The perfusion pressure was reduced by elevation of the intraocular pressure with a Langham's suction cup placed on the temporal sclera. The results showed that the autoregulatory response maintains the macular capillary blood flow velocity until the perfusion pressure is reduced to approximately 25 mmHg. The Closed-loop gain of the autoregulatory response functions at a perfusion pressure as low as approximately 10 mmHg, below which it did not work well. PMID- 2220496 TI - [Aging effects on upper and lower half visual fields by VECPs and automated static perimetry]. AB - We studied the aging effects on upper and lower half visual fields using pattern VECPs with half fields stimuli and automated static perimetry. The subjects, consisting of 56 normal volunteers ranging in age from 10 to 69 years old, were divided into three groups (10-29, 30-49, 50-69 years old). Their visual acuities were better than 1.0 and refractive errors were within +/- 2.0 diopters. Perimetry was performed with an automated perimeter (Octopus, program 61). An artificial pupil of 3 mm was used after cycloplegia with 1% tropicamide to eliminate senile miosis effects in recording of VECPs. Subjective light sensitivity decreased with age and there was a noticeable hiatus between the third and fourth decades. However the age-related decrease in sensitivity showed no difference between the upper and lower half fields. However VECPs results showed that with aging the P100 peak latency did not increase for lower half field stimuli, but increased for the upper half field stimuli, especially for smaller check sizes. These results suggested that there were different aging processes a in the upper and lower half fields and higher neural factors participated in the effects. PMID- 2220497 TI - [A case of orbital hemangiopericytoma]. AB - A 38-year old woman presented with severe proptosis in the left eye which had been developing for more than ten years. CT scan revealed a large mass in the left orbit, therefore lateral orbitotomy was performed. The histopathology of this tumor consisted of ovoid to spindle-shaped cells tumor around a sinusoidal vascular component forming staghorn channels. This tumor was diagnosed as a hemangiopericytoma. The prognosis of orbital hemangiopericytoma including clinicopathological aspects are discussed with reference to recent reports. PMID- 2220498 TI - [Cavum vergae, cyst of cavum septi pellucidi, mega cisterna magna, and general fibrosis syndrome]. AB - One family of 17 cases of general fibrosis syndrome was reported. Four out of five patients examined with CT and/or MRI revealed cavum vergae or cyst of the cavum septi pellucidi or mega cisterna magna, which were characterized by existing on the midline of the brain. The patient with cavum vergae had also platybasia. In one patient, surgical correction of vertical deviation and blepharoptosis of both eyes was performed. There was abnormal insertion of the superior and inferior rectus muscles in posterior and nasal direction, and adhesion of the superior oblique muscle to the superior rectus muscle at the point of it's insertion was found in both eyes. Histopathological findings of the extraocular muscles of two patients showed mixture of relatively normal muscle tissues and vast amounts of collagen fibers. Electron microscopically many glycogen granules were found in muscle fibers. From these findings, this syndrome may be based on failure in development and differentiation. PMID- 2220499 TI - [Mammalian pupil constriction to light in the presence of atropine in hamster. Part I. Hamster and visual rays]. AB - Mammalian pupils constrict in reaction to lights. Miosis occurs via afferent and efferent nerves. Therefore, once the pupil is pretreated with atropine, miosis no longer occurs, even when the retina is intact. We found that hamster pupil constricts in reaction to light in the presence of atropine. We examined the relationship with pupillary size, light intensity, wavelength and intervals of darkness. Pupillary constriction was found when the retina was withdrawn, and the miosis was not affected by autonomic blocking agents, capsaicin pretreatment and tetrodotoxin, a nerve blocking agent. Hamster pupil reacts to lights (visible rays-ultraviolet) in the presence of atropine and in the absence of retinal function. PMID- 2220500 TI - [Effect of ultraviolet light on the hamster pupil]. AB - This is the first study on the effects of ultraviolet light (UV) on the hamster pupil in vivo and in vitro. UV caused constriction of the pupil even after the death of the hamster. Both visible light and UV induced myosis of the enucleated hamster eyes. UV-induced miosis occurred very late and continued after the cessation of UV stimuli. The UV-induced miosis was not significantly affected by ascorbic acid, catalase, allopurinol, but it was gradually inhibited by procaine or quinacrine, phospholipase A2 inhibitors. Withdrawal of Ca2+ and Mg2+ with EGTA and/or EDTA strongly inhibited the UV-induced miosis. This study suggests that the UV-induced miosis was not related to oxidative stress, but related to a second messenger via the muscle cell membrane. PMID- 2220501 TI - [Fundus video fluorescein angiography with low steady light]. AB - To decrease both the intensity of the exciting light and the amount of sodium fluorescein, we attached a compact image intensifier incorporating a microchannel plate with a fundus photoscope and tried to record video-fluorescein angiography with low steady light. We preliminarily examined the relationships of exciting and emitted light intensity with various concentrations of sodium fluorescein. The strongest fluorescence was obtained with a concentration of 0.01 mg/ml solution of sodium fluorescein. When the compact image intensifier was attached to the equipment, the exciting light intensity could be decreased to 1/300 with an exciting filter of lambda max of 486 nm. When sodium fluorescein of 0.01 mg/ml solution was injected directly into the heart of Rana catesbeiana, complete video fluorescein angiography with sufficient brightness and resolution was possible. With the same machine, we recorded video-fluorescein angiography in a normal human subject with injection of 5 ml of 10% sodium fluorescein. The ordinary observing light of the machine was strong enough for video-recording. This exciting light intensity caused no trouble and elicited no complaint from the examinee. These results showed that the use of a compact image intensifier incorporated microchannel plate with a fundus photoscope made it possible to record video-fluorescein angiography and to decrease exciting light intensity and the amount of fluorescein dye. This means that light damage to photoreceptors by exciting light and problems induced by allergic reaction with fluorescein dye might be decreased. These aspects might be very important to obtain information about both retinal circulation and disruption of the blood-retinal barrier and also to perform safe fluorescein angiography examination. PMID- 2220502 TI - [Destruction of anionic sites in blood-retinal barrier after retinal photocoagulation]. AB - The retinal pigment epithelial cells (RPE) have "tight junctions" at the apical side of the lateral wall between neighbouring cells and form physiological blood retinal barriers. Recently, in addition to physiological barriers, charged barriers, consisting of anionic sites of cell membrane and its basement membrane, have been discussed. We performed weak retinal photocoagulation in rabbit eyes in order to break their charged barriers, and examined the repair process using a cationic probe, polyethyleneimine (PEI). Two days after photocoagulation, RPE cells were broken down and choriocapillaries were occluded with thrombi, and their anionic sites were lost. At one week after photocoagulation, structural reconstruction started from the edge of the photocoagulation area. In this area, proliferated RPE cells covered Bruch's membrane, but their charged barrier did not recover. Two weeks after photocoagulation, proliferated RPE cells covered Bruch's membrane over the entire photocoagulated area, and they obtained anionic charge. The present study revealed that retinal damage induced by weak laser photocoagulation was repaired within two weeks after photocoagulation with respect to the charged barrier. PMID- 2220503 TI - [Effect of intravitreal gas on the destruction of anionic sites in the outer blood-retinal barrier]. AB - The present work was undertaken to evaluate the effect of sulfur hexafluoride (SF6) injected intravitreously in rabbit eyes. The alterations of the outer blood retinal barrier that was composed of anionic sites, using a cationic probe, polyethyleneimine (PEI). We injected 0.5 ml of 100% SF6 or 0.5 ml of air into the vitreous cavity of rabbit eyes, and the 0.5% PEI-saline solution was given intravenously at 2, 4, 7, or 14 days after the injection. Control eyes demonstrated numerous PEI-positive sites at the basement membrane of the RPE, collagen fiber of Bruch's membrane, and basement membrane of choriocapillaries. Until seven days after SF6 injection, PEI-positive sites decreased, but had increased at 14 days to control levels, while in air-injected eyes, they had recovered at seven days. SF6 in the vitreous was absorbed in seven days and air in three days. While gas was present in the vitreous, the charge barrier of the outer retina and choroid decreased, but when the gas was absorbed, the charge barrier recovered. The result showed that the decrease of charge barrier was a reversible change. PMID- 2220504 TI - [MRI lesions of the optic nerves in optic neuritis]. AB - Magnetic resonance imaging (MRI) was performed in 14 patients with optic neuritis. Three patients suffered from multiple sclerosis but the etiologies of the remaining 11 cases could not be identified. They were bilateral in 6, and unilateral in 8. The MR images were compared with the symptomatic lesions of optic neuritis and pattern reversal VECP. The STIR mode (short time inversion recovery), was employed for the MRI in the orbit and T2-weighted mode in the brain. In 11 eyes with hyperemia of the optic disc, 7 eyes showed a high signal in the optic nerve with the MRI, and 9 eyes showed an abnormal pattern VECP. Seven eyes with normal disc and two eyes with a pale disc showed a high signal in the optic nerve with MRI, those 9 eyes had abnormal pattern VECP. The high signal in the optic nerve was not related to visual acuity or visual field abnormalities of patients. However, the degree of the high signal of the optic nerve lesion in MRI was associated with the clinical course and prognosis of the optic neuritis. The degree of the high signal of the optic nerve lesion decreased with the recovery of visual acuity in optic neuritis. PMID- 2220505 TI - [Spatial frequency characteristics of upper and lower hemiretina with pattern reversal VECPs]. AB - We studied the spatial frequency characteristics in the upper and lower hemiretina using pattern reversal VECPs. The subjects were 56 normal volunteers ranging in age from 14 to 69 years old. The latency of the first major positive component (P100) of VECPs was measured using checker board pattern stimuli under varying conditions of spatial frequency (112', 56', 28', 14', 7'). For the upper hemiretinal stimuli, the P100 peak latency vs spatial frequencies curve reached minimum at 56' approximately 28' and increased at both lower and higher frequencies. For the lower hemiretinal stimuli, this curve shifted towards lower frequencies. The results suggested that the spatial frequency characteristics between the upper and lower hemiretina were different. PMID- 2220506 TI - [DNA diagnosis of Leber's hereditary optic neuropathy]. AB - The point mutation at nt11778 in mitochondrial DNA is highly associated with Leber's hereditary optic neuropathy and eliminates a restriction enzyme SfaNI site in American blacks and Caucasians. DNA diagnosis was applied to a male Japanese patient with this disorder and his mother as a carrier. The mitochondrial DNA fragments (255bp) including this mutation were amplified by polymerase chain reaction. SfaNI digested the DNA fragments of normal Japanese subjects, but did not digest those of the patient or the carrier, The mutation within the SfaNI site is also associated with Japanese suffering from this disorder. PMID- 2220507 TI - [Serum immunosuppressive acidic protein (IAP) in inflammatory ocular disease]. AB - The titer of serum immunosuppressive acidic protein (IAP) was determined by the method of single radial immunodiffusion (Matsuda et al) in Behcet's disease, sarcoidosis, tuberculosis, toxoplasmosis, etiology-unknown anterior uveitis (granulomatous, non-granulomatous), allergic conjunctivitis and scleritis. The titer of IAP in these diseases except allergic conjunctivitis was significantly higher than in normal controls. In all the diseases studied, the titer during the active stage was significantly higher than that during the inactive stage. The titer in Behcet's disease was significantly higher than that in sarcoidosis, particularly during the active stage. In three cases of Behcet's disease, the titer was increased markedly a few days before the ocular attacks. There was no difference in the titer between etiology-unknown granulomatous and non granulomatous anterior uveitis. IAP may be useful as a clinical index in inflammatory ocular diseases. PMID- 2220508 TI - [A case of Rubinstein-Taybi syndrome suspected with goniodysgenetic glaucoma]. AB - We reported a case of Rubinstein-Taybi syndrome suspected in association with goniodysgenetic glaucoma, and studied using light and electron microscopy the anterior chamber angle tissues obtained surgically by trabeculectomy. The patient was 31-year old male, who had a systemic appearance of Rubinstein-Taybi syndrome with dwarfism, mental retardation, antimongoloid slant, flat-broad based thumbs, low set ears, high arched plate except for whorl of dermatographism. In addition to these malformations, goniodysgenetic glaucoma was also present which is characterized by underdevelopment of the angle recess and invisible ciliary body band in gonioscopic examination. The histopathological studies of the specimens revealed the presence of a compact tissue filled with a large amount of collagen fibers with few cells in the juxta-canalicular tissue of Schlemm's canal. There were 3 to 4 layers of trabecular sheets of corneoscleral meshwork at the anterior chamber side of the compact tissue. We conclude that the presence of the compact tissue under Schlemm's canal represents goniodysgenesis, underdevelopment of the trabecular meshwork, which is the primary cause of the glaucoma in this case. PMID- 2220510 TI - How to help your patients stop smoking. AB - Family physicians can effectively help their patients stop smoking by using brief intervention and simple office organizational procedures. Intervention involves asking all patients about smoking, advising smokers to stop, assisting with self help materials, establishing a date for quitting, possibly prescribing nicotine gum and, finally, arranging for follow-up visits. Office procedures include selecting an office coordinator, ensuring a smoke-free office, establishing a mechanism to identify and monitor patients who smoke, and involving the office staff in intervention and follow-up. With this protocol, intervention is possible at every office visit. PMID- 2220509 TI - Inhaler and spacer use in obstructive airway diseases. AB - The role of inhaled aerosols in the treatment of obstructive airway diseases is increasing for both immediate bronchodilation and prophylactic anti-inflammatory effects. Inhaled aerosol agents are available in metered-dose inhaler and nebulizer forms. Maximum therapeutic benefit from metered-dose inhalers is assured when the correct inhaler technique is used. Spacer devices may be helpful in some patients. PMID- 2220511 TI - Puffer fish poisoning. AB - Regarded by many as a delicacy, puffer fish can be the source of lethal food poisoning in humans. The syndrome is caused by tetrodotoxin, one of the most potent poisons known. Intoxication produces a constellation of symptoms, with paresthesias and generalized muscle weakness being common complaints. Treatment is symptomatic and often needs to be aggressive. Life support may be required. In some series, the mortality rate has approached 60 percent. PMID- 2220513 TI - Desmopressin for diabetes insipidus, hemostatic disorders and enuresis. AB - Arginine vasopressin preparations have been used in the treatment of diabetes insipidus for many years. Compared with older antidiuretic agents, the synthetic analog desmopressin is more potent, longer acting and easier to use. It is available for intravenous, subcutaneous and intranasal administration. Desmopressin may be useful in the treatment of hemostatic disorders such as von Willebrand's disease and hemophilia A. It has also been used for nocturnal enuresis. The vasopressor effects of arginine vasopressin preparations have been exploited for use as a temporizing measure in controlling acute gastrointestinal bleeding. Side effects such as hyponatremia and water intoxication are uncommon when these drugs are used with proper precautions. PMID- 2220512 TI - Update on combination oral contraceptives. AB - Oral contraceptives in current use appear to be safe and effective. Studies found that early contraceptive pills, which had a high estrogen content, were associated with a number of serious side effects and long-term sequelae. Studies of the newer low-dose preparations demonstrate a much lower incidence of adverse effects. The beneficial effects of oral contraceptives in disease prevention are now widely recognized. The diversity of available formulations allows the physician to tailor therapy to the individual patient, maintaining contraceptive efficacy while minimizing adverse effects and long-term risks. PMID- 2220514 TI - Abnormal eye movements may be first sign of HIV disease. PMID- 2220516 TI - Recent ACOG bulletin covers management of postpartum hemorrhage. PMID- 2220515 TI - AAFP position statement: ethical 'need to know' considerations in HIV infection. The Committee on Medical Ethics. PMID- 2220518 TI - Series of family doctor CHATS begins with AIDS education. PMID- 2220517 TI - Facing the challenge of laboratory regulation. PMID- 2220519 TI - Value of serum chemistry testing. PMID- 2220520 TI - MRI and claustrophobia. PMID- 2220521 TI - HIV infection: the dilemma of patient confidentiality. PMID- 2220522 TI - The family physician's role in helping older smokers quit. PMID- 2220523 TI - Changing attitudes toward tobacco and its promotion. PMID- 2220524 TI - HIV disease: a review for the family physician. Part I. Evaluation and conventional therapy. AB - Family physicians will be challenged with caring for increasing numbers of patients infected with human immunodeficiency virus. After confirming the presence of the infection, the physician must follow a logical sequence of evaluation, counseling and treatment. The current Centers for Disease Control classification and a series of evaluation and treatment protocols form the basis for prescribing zidovudine to delay or mitigate involvement of T lymphocytes and neuronal cells. PMID- 2220525 TI - Screening for prostate cancer. The U.S. Preventive Services Task Force. PMID- 2220526 TI - Ascariasis. AB - Ascaris lumbricoides is the most common helminth to infect humans. Infection occurs when contaminated soil containing mature eggs is swallowed. Clinically, infection ranges from the asymptomatic carrier state to life-threatening pulmonary disease or intestinal obstruction. Diagnosis is most frequently established by identification of the eggs in stool specimens. Treatment with antiparasitic drugs is effective in preventing serious complications and eradicating the parasite from all members of the household. PMID- 2220527 TI - Pseudoaneurysm of a Shiley composite aortic valve and graft prosthesis. PMID- 2220528 TI - Echocardiographic diagnosis of rheumatic cardiopathy affecting all four cardiac valves. PMID- 2220529 TI - Acute combined aortic and mitral regurgitation during balloon catheter valvuloplasty for a third recurrence of critical aortic stenosis. PMID- 2220530 TI - Assessment of myocardial viability. PMID- 2220531 TI - Time delays in the diagnosis and treatment of acute myocardial infarction: a tale of eight cities. Report from the Pre-hospital Study Group and the Cincinnati Heart Project. AB - To establish the magnitude of prehospital and hospital delays in initiating thrombolytic therapy for acute myocardial infarction, the time from telephone 911 emergency medical system (EMS) activation to treatment and its components were analyzed from eight separate ongoing trials. This included estimates of ambulance response time, prehospital evaluation and treatment time, and time from admission to the hospital to initiation of thrombolytic therapy. The average time from EMS activation to patient arrival at the hospital was prospectively determined to be 46.1 +/- 8.2 minutes in 3715 patients from eight centers. The time from admission to the hospital to initiation of thrombolytic therapy was retrospectively determined to be 83.8 +/- 55.0 minutes in a separate group of 730 patients from six centers. Both the prehospital and hospital time delays were much longer than those perceived by paramedics and emergency department directors. Shorter hospital time delays were observed in patients in whom a prehospital ECG was obtained as part of a protocol-driven prehospital diagnostic strategy and a diagnosis of acute infarction made before arrival at the hospital (36.3 +/- 11.3 minutes in 13 patients). These results show that the magnitude of time required to evaluate, transport, and initiate thrombolytic therapy will preclude initiation of treatment to most patients within the first hour of symptoms. Implementation of a protocol-driven prehospital diagnostic strategy may be associated with a reduction in time to thrombolytic therapy. PMID- 2220532 TI - Assay of serum cardiac myosin heavy chain fragments in patients with acute myocardial infarction: determination of infarct size and long-term follow-up. AB - To evaluate the correlation between myosin heavy chain release and the necrosis mass, serum levels of myosin heavy chain fragments were determined serially in 55 patients with acute myocardial infarction. Eight of these patients were successfully treated with thrombolytic agents: the others were not treated. The same myosin titration was applied to the sera of 25 dogs with an experimental myocardial infarction. Six of the dogs were successfully treated with thrombolytic agents. The time courses of the myosin concentrations are typical and monophasic for all patients with a noncomplex myocardial infarction. The values for the kinetic parameters of myosin release are comparable to those previously reported. We have now determined that cumulative myosin release significantly correlates with cumulative creatine kinase (CK), CK-MB, and lactate dehydrogenase release, as well as with thallium-201 distribution, as determined for different patient groups. Thrombolytic treatment does not seem to qualitatively upset myosin kinetics. The results obtained in dogs with or without thrombolysis conclusively indicate that myosin release is a quantitative index of the necrosis mass. From a practical point of view, a few serial determinations of serum levels of myosin heavy chains are enough to estimate the necrosed mass in patients with acute myocardial infarction. More generally, serum myosin titration could be useful in detecting any cardiac disturbance involving myocardial injury resulting in membrane leakage of cardiac cells. PMID- 2220533 TI - Reduction in infarct size by the phospholipase inhibitor quinacrine in dogs with coronary artery occlusion. AB - It has been suggested that activation of tissue phospholipases may contribute to the development of ischemic cell injury. In the present study we sought to assess whether administration of the phospholipase inhibitor quinacrine would reduce the extent of myocardial necrosis after coronary artery occlusion. In open-chest, anesthetized dogs the left anterior descending coronary artery was ligated, and technetium-99-labeled albumin microspheres were injected into the left atrium to measure the area at risk. The animals were then randomly divided into a control group (n = 8) and a group receiving quinacrine (5 mg/kg intravenous bolus followed by a 40 micrograms/kg/min infusion for 6 hours; n = 9). The animals were killed 6 hours after occlusion, and the infarcted area was delineated by triphenyltetrazolium chloride staining. The extent of the risk region was similar in the two groups (32.3 +/- 2.1% of the left ventricle in control dogs and 34.2 +/- 3.4% in quinacrine-treated dogs). Infarct size was 86.4 +/- 8.8% of the risk region in control animals, whereas in treated dogs it averaged 62.3 +/- 6.4% of the risk region (p = 0.05). No differences were found in heart rate, arterial pressure, and rate-pressure product between the two groups. Thus administration of the phospholipase inhibitor quinacrine reduced the extent of myocardial necrosis in a model of fixed coronary artery occlusion. Preservation of membrane phospholipids, reduced formation of lipoxygenase metabolites, or both may mediate this phenomenon. PMID- 2220534 TI - Intracoronary adenosine administration during reperfusion following 3 hours of ischemia: effects on infarct size, ventricular function, and regional myocardial blood flow. AB - Previous studies have demonstrated that adenosine significantly enhances myocardial salvage after 90 minutes of regional ischemia. To determine its effect after prolonged ischemia, closed-chest dogs underwent 3 hours of left anterior descending artery occlusion followed by 72 hours of reperfusion. Intracoronary adenosine (3.75 mg/min; at 1.5 ml/min:total volume = 90 ml; n = 10) or an equivalent volume of saline (1.5 ml/min: total volume = 90 ml; n = 9) was infused into the left main coronary artery during the first 60 minutes of reperfusion. Regional myocardial blood flow was assessed serially with microspheres and regional ventricular function was assessed by contrast ventriculography. Infarct size was determined histologically. Light and electron microscopy were utilized to assess neutrophil infiltration and microvascular injury. Adenosine failed to reduce infarct size expressed as a percentage of the area at risk (38.0 +/- 4.9% versus 34.8 +/- 4.6%; p = NS) or to improve regional ventricular function as measured by the radial shortening method (3.2 +/- 1.8% versus 2.2 +/- 3.1%; p = NS) at 72 hours after reperfusion. Vasodilatory effects were not observed in the endo- and midmyocardial regions of the ischemic zone during adenosine administration. This was associated with a similar extent of capillary endothelial changes and neutrophil infiltration in both adenosine-treated and saline control groups. These results suggest that severe functional abnormalities are present in the vasculature after 3 hours of ischemia and that adenosine therapy is ineffective in enhancing myocardial salvage. PMID- 2220535 TI - Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia. AB - To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220536 TI - Comparison of coronary angiography and early oral dipyridamole thallium-201 scintigraphy in patients receiving thrombolytic therapy for acute myocardial infarction. AB - We evaluated 50 consecutive patients who received thrombolytic therapy for acute myocardial infarction using thallium-201 single photon emission computed tomography in combination with oral dipyridamole (300 mg) to assess the frequency of residual myocardial ischemia. Thallium studies were performed early after myocardial infarction at a mean of 4.6 days (range 3 to 11) in 50 patients. The time from the onset of chest pain to the administration of thrombolytic therapy was 2.6 hours (range 0.5 to 5.5). Q wave myocardial infarction was evident in 46 patients; four patients had a non-Q wave infarction (anterior infarction in 31 patients and inferior infarction in 19 patients). The serum mean peak creatinine kinase was 1503 IU/L (range 127 to 6500). Coronary angiography was performed in all patients at a mean of 3.1 days (range 2 to 10) and revealed the infarct related vessel to be patent in 36 patients (72%). The ejection fraction was 48% (range 26% to 67%). After dipyridamole administration, 13 patients (26%) developed angina that was easily reversed with the administration of intravenous aminophylline. Systolic blood pressure decreased from 122 to 115 mm Hg (p less than 0.05) and the heart rate increased from 76 to 85 beats/min (p less than 0.05). None of the patients had significant hypotension, arrhythmias, or evidence of infarct extension. Perfusion abnormalities were present on the initial thallium images in 48 patients. Redistribution suggestive of ischemia was present in 36 patients (72%). Ischemia confined to the vascular distribution of the infarct vessel was evident in 22 patients. Seven patients had ischemia in the infarct zone as well as in a remote myocardial segment. Thus 29 patients (58%) had ischemia in the distribution of the infarct vessel. Ischemia in the infarct zone was evident in 19 of 36 patients (53%) with open infarct vessels and in 10 of 14 patients (71%) with occluded infarct vessels. In conclusion, thallium-201 single photon emission computed tomography using oral dipyridamole was safely performed in patients with recent myocardial infarctions who receive thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220537 TI - Similar time course of ST depression during and after exercise in patients with coronary artery disease and syndrome X. AB - To assess whether the time course of ST segment depression differs in patients with coronary artery disease and patients with angina and normal coronary arteries, the exercise tests of 54 patients with documented coronary artery disease and 25 patients with syndrome X (angina, positive exercise test, no evidence of coronary artery spasm, and normal coronary arteries) were compared. All tests were performed with therapy withheld, using the modified Bruce protocol. In each test, time, heart rate and blood pressure were measured at the onset and at 1 mm of ST segment depression, and at peak exercise. Recovery (return of the ST segment to baseline +/- 0.2 mm) time was also assessed. Peak ST segment depression was similar in coronary artery disease and syndrome X patients (1.5 +/- 0.3 versus 1.6 +/- 0.4 mm). In 42 coronary artery disease patients, ST segment depression developed early (less than or equal to 6 minutes) during exercise; this was associated with a short recovery (less than or equal to 3 minutes) in 17 (40%) and with a long recovery (greater than 3 minutes) in 25 (60%) patients. In 17 patients with syndrome X, ST segment depression developed early; it was associated with a short recovery in six (35%) and with a long recovery in 11 (65%) patients. Late (greater than 6 minutes) onset of ST segment depression was observed in 12 coronary artery disease patients; of these, eight (67%) had a short recovery and 4 (33%) had a long recovery. Late onset of ST segment depression occurred in eight patients with syndrome X; six (75%) had a short recovery and two (25%) had a long recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220538 TI - Prolongation of ventricular refractoriness by class Ia antiarrhythmic drugs in the prevention of ventricular tachycardia induction. AB - The effects of class la antiarrhythmic drugs (procainamide, quinidine) on the right ventricular effective refractory period (VERP) and intraventricular conduction time were assessed during serial invasive electrophysiologic studies for sustained monomorphic ventricular tachycardia (VT). In 47 patients with remote myocardial infarction, sustained VT was inducible by up to two extrastimuli after the basic drive at one of two basic cycle lengths at the right ventricular apex. With oral drug administration, sustained VT was no longer inducible (group I) in 27 patients but remained inducible (group II) in 20 with the same protocol. Class la drugs prolonged the VERP in both groups, but there was greater lengthening when drugs were effective (e.g., +32 +/- 14 msec in group I vs +12 +/- 19 msec in group II; p less than 0.005, basic cycle length 600 to 700 msec). Prolongation of the VERP by greater than 30 msec had an 88% positive predictive value for prevention of sustained VT induction. In all except one patient in group I, drugs prolonged the VERP such that the coupling intervals that had resulted in sustained VT induction under control conditions were no longer attainable. In contrast, conduction time through the ventricle (surface QRS duration) in sinus rhythm and during right ventricular pacing was prolonged similarly regardless of efficacy (e.g., +33 +/- 21 msec vs +27 +/- 27 msec at a cycle length of 400 msec). The presence of similar plasma levels of drug did not imply equivalent prolongation of the VERP in the two groups. These results suggest that greater prolongation of the VERP by oral procainamide or quinidine correlates with drug efficacy against VT induction and is a better predictor of drug effect than achievement of a "therapeutic plasma level." PMID- 2220539 TI - Lesions in side branches of arteries having undergone percutaneous transluminal coronary angioplasty: a histopathologic study. AB - Percutaneous transluminal coronary angioplasty (PTCA) may cause occlusion in side branches. No histologic studies, however, have been made on side branches of the arteries in which PTCA has been performed. A histologic study was therefore made to explain the effect of PTCA on side branches. Histologic specimens were prepared by serial step sectioning from 15 side branches of 10 autopsied cases that had undergone PTCA. The results of examination by light microscope were as follows: (1) Stenoses due to PTCA were seen in seven branches (46.7%). (2) The stenoses were classified into three types: (a) stenosis due to blocking of the orifice of a side branch by the disrupted portion of the intima of the main artery (one branch); (b) stenosis due to medial dissection of the main artery or further dissection occurring even in the side branches (three branches); and (c) stenosis due to fragmentation of the internal elastic lamina of the main artery accompanied by proliferation of smooth muscle cells even in the side branch (three branches). It is now clear that stenosis is caused in side branches long after PTCA. Extra care is required when major side branches exist in the portion where this procedure is to be performed. PMID- 2220540 TI - Residual atrial septal perforation after percutaneous transvenous mitral commissurotomy with Inoue balloon catheter. AB - To estimate the incidence of residual atrial septal perforation (ASP) following percutaneous transvenous mitral commissurotomy (PTMC) with the Inoue balloon catheter and to examine the factors contributing to ASP, we studied 46 patients with mitral stenosis undergoing PTMC. Residual ASP was evaluated by Doppler color flow imaging 1 day after PTMC, and was detected in 7 out of 46 patients (15.2%). We examined the relationship between the development of ASP (ASP+) and the age of the patient, the left atrial dimension before PTMC, the mean pressure difference between left and right atrium after PTMC, and the duration of the procedure from atrial septal puncture by the Brockenbrough method to balloon inflation. There was a good correlation between the development of residual ASP and the duration of the procedure (ASP+, 51.0 +/- 34.0 minutes; without ASP, 24.6 +/- 16.2 minutes; p less than 0.01). However, there was no significant correlation between the development of ASP and other factors. In the follow-up study, ASP disappeared in four patients within 3 months. ASP persisted in two patients for 1 year after PTMC. However, the shunt in these two patients was clinically insignificant. These data suggest that residual ASP may depend on the duration of the procedure, and that most cases of ASP disappear within 1 year after PTMC. PMID- 2220541 TI - Results of repeat percutaneous balloon valvuloplasty for pulmonary valvar restenosis. AB - Follow-up cardiac catheterization studies were used to evaluate 105 patients who had undergone percutaneous balloon pulmonary valvuloplasty. Fifteen of those patients who had peak systolic pulmonary valve gradients greater than = 40 mm Hg at follow-up underwent repeat balloon valvuloplasty. For the initial balloon pulmonary valvuloplasty, the mean ratio of the balloon diameter to pulmonary valve annulus diameter was 0.98 +/- 0.2; at repeat valvuloplasty the mean was 1.19 +/- 0.12. The immediate post-repeat balloon valvuloplasty results showed a reduction in the peak systolic gradient from a mean of 70.2 +/- 17.8 to 29.1 +/- 19.0 mm Hg (p less than 0.001). This reduction in the gradient was maintained at a mean of 14.3 +/- 5.0 mm Hg in 8 of the 10 patients who underwent further follow up studies. We conclude that successful repeat balloon pulmonary valvuloplasty with the use of larger sized balloons is feasible in patients who have restenosis after the initial percutaneous balloon valvuloplasty--including partial but not complete dysplasia of the pulmonary valve. PMID- 2220542 TI - Noninvasive discrimination of right atrial ectopic tachycardia from sinus tachycardia in "dilated cardiomyopathy". AB - Right atrial ectopic tachycardia (RAET) with secondary cardiac dysfunction can be difficult to differentiate from primary dilated cardiomyopathy (CMP) with sinus tachycardia. In an attempt to separate RAET from CMP by noninvasive testing, routine surface electrocardiograms (EGGs), 24-hour ambulatory ECGs (Holter monitors), and echocardiograms of patients with RAET (n = 34) and CMP (n = 33) were reviewed. RAET atrial rates were significantly faster than CMP rates on the resting ECG and on Holter monitoring; 12 of 33 patients with RAET had resting ECG rates greater than 150% of predicted normal values for age but none of 32 patients with CMPs had resting ECG rates in this range. Mean P wave axis in the horizontal plane was more posterior in patients with RAET and was less than 0 degrees (negative in lead V2) in 8 of 29 patients with RAET but in 1 of 33 patients with CMP. Second-degree atrioventricular (AV) block was observed in 12 of 33 patients with RAET but in none of 33 with CMP. Shortening fraction less than 10% was found in 13 of 33 individuals with CMP but in only 1 of 27 with RAET. We conclude that noninvasive studies can help identify RAET among patients with poor functioning hearts and right atrial tachycardia. PMID- 2220543 TI - Left ventricular end-systolic stress-volume index ratio in aortic and mitral regurgitation with normal ejection fraction. AB - To evaluate the left ventricular contractile state in regurgitant valvular disease with normal ejection fraction, we analyzed the end-systolic stress-volume index relationship (ESSVR) by means of cineangiography in 15 normal subjects, 11 patients with aortic regurgitation (AR), and 10 patients with mitral regurgitation (MR) whose ejection fraction (EF) was 60% or more. The end-systolic stress-volume index ratio in normal subjects was 5.57 +/- 0.60 kdyne/cm5/m2 (mean +/- standard deviation), and we defined the range including +/- 2 standard deviations of the ratio as the normal ESSVR range. Six patients with AR and five patients with MR placed inside the normal ESSVR range, termed AR IN and MR IN, but the remaining five patients with AR and MR placed to the right of the normal range, termed AR OUT and MR OUT. EF did not differ between patients with AR IN and AR OUT (69.4 +/- 5.4 verus 70.7 +/- 6.1%) and between MR IN and MR OUT (71.6 +/- 3.6 versus 71.1 +/- 7.9%). The EF of the subdivided groups with AR and MR also did not differ from that of normal subjects (70.7 +/- 7.3%). This finding showed that the left ventricular contractile state was depressed in patients with AR OUT and MR OUT despite a normal EF. In AR and MR the end-systolic stress and end-systolic volume index of OUT did not differ from those of IN, but the end diastolic volume index of OUT was larger than that of IN (AR OUT 156.8 +/- 27.9 versus AR IN 110.8 +/- 24.1 ml/m2, MR OUT 160.5 +/- 44.7 versus MR IN 101.0 +/ 16.6 ml/m2; both p less than 0.05), and the regurgitant fraction of OUT was higher than that of IN (AR OUT 52.6 +/- 13.6 versus AR IN 29.7 +/- 13.3%, MR OUT 52.9 +/- 10.2 versus MR IN 30.2 +/- 11.4%; both p less than 0.05). In addition, there was a linear inverse correlation between the end-systolic stress-volume index ratio and the end-diastolic volume index in all subjects (r = -0.82, n = 36). In normal subjects there was a linear inverse correlation between end systolic stress and the EF (r = -0.91, n = 15), but this relationship failed to separate patients with OUT from those with IN. Results of the present study suggest that some patients with AR and MR whose EF was normal had a depressed contractile state, and these patients had a large end-diastolic volume index and a high regurgitant fraction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2220544 TI - Maximal oxygen uptake in severe aortic regurgitation: a different view of left ventricular function. AB - Respiratory gas exchange was used to assess left ventricular (LV) function in 22 patients with severe aortic regurgitation (19 men and three women, aged 18 and 70 years, mean 49 years). Anaerobic threshold and symptom-limited maximal oxygen consumption (VO2 max) were measured during treadmill exercise, and the results were compared with conventional echocardiographic and radionuclide indices of LV systolic function. The results were considered with respect to the patients' New York Heart Association functional class. Both rest and exercise LV ejection fractions were variable, but the mean results were similar in all classes. The echocardiographic indices of LV cavity dimensions, fractional shortening, radius/thickness ratio, and systolic wall stress also showed a wide range but with similar mean results in each class. In contrast, VO2 max and anaerobic threshold showed a relationship to functional class. VO2 max was 32.4 +/- 3.4 ml/kg/min in age-matched control subjects; in the patients it was 27.9 +/- 4.7 in class I, 24.7 +/- 5.7 in class II, and 14.2 +/- 2 in the combined class III/IV. Results in patients in classes I and II were similar, but both groups were significantly different from control subjects (p less than 0.05) and from patients in class III/IV (p less than 0.01). About half of the patients with moderate LV dysfunction (judged by reduced VO2 max) were asymptomatic, and LV function was impaired in 4 of 10 patients in class I. Thus, unlike conventional indices of LV function, VO2 max appeared capable of distinguishing patients with moderate-to-severe LV dysfunction from those with little or no LV dysfunction. Measurement of respiratory gas exchange appears to be a valid and useful supplementary means of assessing LV function in severe aortic regurgitation. Further long-term evaluation is required. PMID- 2220545 TI - Contribution of transesophageal echocardiography to patient diagnosis and treatment: a prospective analysis. AB - The capability of transesophageal (TEE) versus transthoracic (TTE) echocardiography as a diagnostic tool in clinical practice was prospectively examined in 86 consecutive cases. A conclusive diagnosis was possible in 95% with TEE, whereas the same result was achieved in 48% by TTE. Specifically, TEE provided a conclusive diagnosis in 14 of 16 cases of infective endocarditis, while TTE gave this result in 4 of the 16 cases (p less than 0.001). Similarly, TEE allowed a conclusive diagnosis in 11 of 11 instances of aortic dissection, while TTE gave this indication in two cases (p less than 0.001). TEE was similarly effective in eight of eight cases of atrial thrombi, whereas TTE gave the diagnosis in three of eight cases (p less than 0.01). In five subjects with intracardiac masses, TEE gave a conclusive diagnosis in all five, whereas TTE was able to diagnose conclusively in one subject (p less than 0.02). In seven patients with mitral regurgitation, TEE gave the conclusive diagnosis in all seven and TTE was able to provide this information in four (p = NS). TEE was able to provide a conclusive diagnosis in four patients with aortic insufficiency, and TTE gave the same information in two of the four (p = NS). In 14 patients with prosthetic valve dysfunction, TEE gave the diagnosis in 12 and TTE gave it in eight patients (p = NS). Both methods gave a conclusive diagnosis in 13 out of 13 cases of mitral stenosis (p = NS). Also, TEE provided a conclusive diagnosis in eight of eight patients with adult congenital heart disease and TTE gave this information in four (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220546 TI - Spontaneous echocardiographic contrast in the descending aorta. AB - The visualization of echocardiographic spontaneous contrast is a common phenomenon in patients undergoing transesophageal echocardiographic studies. Its pathophysiology is not well understood, but it has been related to the presence of a low flow state in the cardiac chambers. We report the presence of spontaneous contrast in the descending aorta of four patients, a location not previously described in the absence of aortic dissection. In two patients, spontaneous contrast was noted in both the left atrium and the descending aorta. In one patient with moderate left ventricular dysfunction, spontaneous contrast was noted in the descending aorta and in the left ventricle. In the remaining case, no cardiac or aortic abnormalities were observed and this represents the first time that spontaneous contrast has been identified in a patient with an echocardiographically normal heart. The occurrence of spontaneous contrast has been considered an abnormal echocardiographic finding, since it has always been described in patients with clinical symptoms and cardiac abnormalities. The fact that spontaneous contrast can be visualized in patients with very mild structural cardiac abnormalities or none at all, warrants further investigation, especially when therapeutic or prognostic implications are considered. PMID- 2220547 TI - Marfan syndrome in China: a collective review of 564 cases among 98 families. AB - This is a collective review of 564 patients with Marfan syndrome among 98 pedigrees reported from 18 provinces and cities in China over a 37-year period from 1951 to 1987. A positive family history of Marfan syndrome was found in 74.3% of the patients: the mode of inheritance was dominant in 73.8% and recessive in 0.5%. Sporadic cases occurred in 25.7%. A screening of 29,067 children found five children with Marfan syndrome, giving a prevalence of 17.2 per 100,000 of the population, a gene frequency of 8.61 per 100,000 genes, and a penetrance of 71.69%. Pleiotropy was clear in these cases: arachnodactyly in 77%, ectopia lentis in 86.8%, and dilated aortic root in 80.1%. Chromosome examination showed no regular aberrations except in a family of five in whom a giant satellited chromosome 14 was found in three afflicted members but not in the two unaffected relatives. The high prevalence of aortic root dilation in Marfan syndrome makes echocardiography the most useful and practical means of diagnosis. Close follow-up and regular echocardiographic evaluation are indicated not only in patients with Marfan syndrome but also in their families, for both diagnostic and therapeutic purposes. PMID- 2220548 TI - Atrial septal aneurysm: recognition and clinical relevance. PMID- 2220549 TI - Parental history is an independent risk factor for coronary artery disease: the Framingham Study. AB - Family history of CAD, defined as parental death by CAD, was found to be a significant independent predictor of CAD in a logistic regression model controlling for standard risk factors and length of follow-up among the 5209 participants in the Framingham Study. Persons with a positive parental history have a 29% increased risk of CAD, and the strength of the association between parental history and CAD is similar to that found for other standard risk factors such as systolic blood pressure, cholesterol level, and cigarette smoking. No evidence was found that persons with a family history of CAD have a decreased capacity to cope with the deleterious effects of known risk factors; that is, no significant interaction was found between any of the risk factors and parental history of CAD. Among men with low risk for CAD by risk-factor profile (i.e., nonsmoking, thin, nonhypertensive persons), more than two thirds of those who experience CAD have a positive parental history. This study suggests that CAD among persons who are predicted to be at low risk by standard risk factors may have a substantial genetic component and that the risk associated with parental history may not be reduced by modification of these factors. Nevertheless, among persons with a positive family history, those with a favorable risk profile are at substantially less risk for CAD than those with an unfavorable risk profile. PMID- 2220550 TI - Successful coronary angioplasty in two patients with cardiogenic shock using the Nimbus Hemopump support device. PMID- 2220551 TI - Delayed complete heart block complicating percutaneous transluminal coronary angioplasty. PMID- 2220552 TI - Cocaine-induced torsades de pointes in a patient with the idiopathic long QT syndrome. PMID- 2220553 TI - Conduction system disease in a child with long QT syndrome. PMID- 2220554 TI - AV blockade via selective AV nodal artery injection in a patient. PMID- 2220555 TI - Spontaneous echo contrast in the left atrium during paroxysmal atrial fibrillation. PMID- 2220556 TI - Left ventricular pseudoaneurysm: detection and postoperative follow-up by color Doppler echocardiography. PMID- 2220557 TI - Congenital left atrial appendage aneurysm with intact pericardium: diagnosis by transesophageal echocardiography. PMID- 2220559 TI - Persistent left superior vena cava: unusual wave contour of left jugular vein as the presenting feature. PMID- 2220558 TI - Cardiac manifestations of Churg-Strauss syndrome: report of a case and review of the literature. PMID- 2220560 TI - APhA announces national DUR program. PMID- 2220561 TI - Update on quinolone drug interactions. AB - Concurrent administration of both ciprofloxacin and norfloxacin with sucralfate leads to a decrease in quinolone bioavailability. It is unknown whether this decrease is clinically significant because studies have focused primarily on pharmacokinetics and not therapeutic outcomes. A reasonable recommendation may be to avoid using sucralfate and norfloxacin concurrently, or avoid administration of norfloxacin and ciprofloxacin within two hours of sucralfate administration. Magnesium- and aluminum-containing antacids may also interfere with quinolone absorption. Calcium carbonate and H2 receptor antagonists do not appear to interact with quinolones and may be considered as an alternative to sucralfate or magnesium- and aluminum-containing antacids when quinolones are administered. Concurrent administration of ciprofloxacin and theophylline may precipitate theophylline toxicity if not monitored carefully. Some clinicians recommend a 30% empiric reduction in theophylline dosage when ciprofloxacin therapy is initiated. Because the drug interaction is not completely predictable, the patient's theophylline levels should be monitored and signs and symptoms of toxicity noted, adjusting the dose as needed. Decreased theophylline clearance may persist for as long as five days following discontinuation of ciprofloxacin. Some potential for slight increases in serum theophylline concentrations secondary to norfloxacin administration may exist. However, it is unlikely to be clinically significant, based on currently available information. PMID- 2220562 TI - Path through the job jungle: Part 2. The hunt is on. PMID- 2220563 TI - 'Drug' is not a four-letter word. PMID- 2220564 TI - Noise exposure reduction aboard an oceangoing hopper dredge. AB - Reported industrial hygiene surveys aboard seagoing vessels are few, despite the presence of many potentially hazardous chemical and physical agents aboard ships. This investigation focused on crew noise exposure aboard an oceangoing hopper dredge. Noise exposure criteria were adopted based on the 24-hr equivalent continuous sound level (Leq(24)) because of the absence of standards for U.S. shipboard noise exposure. Personal noise dosimeters were used to measure the noise exposure of watchstanders, whose duties were predictable and repetitive. Watchstanders with high noise doses were asked to estimate their duration of exposure in specific areas of the vessel to enable calculation of noise dose per space. Noise sources within spaces associated with high noise dose were identified by sound pressure and surface vibration analysis in octave bands. Almost all accommodation spaces (cabins, recreation rooms, dining rooms, and hospital) were sufficiently quiet (sound pressure levels [SPLs] less than 65 dBA) to permit hearing threshold recovery. Machinery space SPLs ranged from 85 to 108 dBA, and engineering personnel noise exposure exceeded the selected criterion of Leq(24) = 80 dBA. Selective noise abatement and use of an enclosed operating station in the engine room were recommended to control engineering personnel noise exposure. This approach to noise exposure assessment and reduction should be applicable to other oceangoing ships where personnel may be exposed to noise 24 hr per day for weeks at a time. PMID- 2220565 TI - PPG's Safety and Health Index System: a 10-year update of an in-plant Hazardous Materials Identification System and its relationship to finished product labeling, industrial hygiene, and medical programs. AB - The Safety and Health Index System (SHIS) has developed beyond its initial role as an in-plant labeling system. It has evolved into a classification scheme to rank the hazards found in the workplace and is useful in prioritizing industrial hygiene monitoring programs, installation of engineering controls, and implementation of medical monitoring for chronic hazards. In addition to providing objective criteria on which to evaluate physical and acute health hazards, this system addresses chronic health hazards such as carcinogens, mutagens, teratogens, and reproductive toxins. PMID- 2220566 TI - Using noise exposure histories to quantify duration of vibration exposure in tree fallers. AB - A study of tree fallers in the British Columbia forest industry was done to determine if noise histories could be used to monitor the daily duration of exposure to hand-arm vibration from chain saws. Field observations and noise dosimetry showed that chain saw noise was distinguishable from other sound sources in fallers' work environments. Using data from noise dosimetry synchronized with observations of fallers' chain saw use, a model of sound pressure levels predictive of chain saw operating mode was developed. Subsequent workday noise histories of 13 fallers showed that the chain saw was off for an average of 331 +/- 27 min, idling for 91 +/- 11 min, and cutting wood for 96 +/- 7 min. This method could be used to collect data to refine dose-response estimates for vibration syndrome or to monitor administrative controls of vibration exposure time. PMID- 2220567 TI - A predictive model for vapor concentration in a nose-only inhalation chamber. AB - A unique nose-only inhalation chamber was designed and constructed to deliver uniform concentrations of gas, vapor, and aerosol contaminants to mice. This research investigated the fluid dynamics of a vaporous contaminant in the vertical flow chamber. The vapor was introduced by allowing the liquid phase of the contaminant to evaporate freely into the chamber interior. A contaminant mass transfer model was developed to predict concentrations generated by the system. The mathematical model of the system used clean airflow, liquid surface area, thickness of the stagnant air layer covering the liquid, system pressure, contaminant diffusion coefficient, and contaminant vapor pressure to compute the vapor concentration delivered to exposure ports. The equation was verified by placing various containers of methyl isobutyl ketone in the chamber and determining with a photospectrometer the resulting equilibrium concentrations. Vapor pressure, diffusion coefficient, and system pressure were held constant while airflow, surface area, and stagnant air layer thickness were varied systematically within the chamber. The resulting empirical data points were compared to the curves predicted by the theoretical model. Empirical concentrations fell within 0 to 48% of the theoretical values, showing that the equation can be used to choose values for airflow, surface area, and stagnant air layer thickness that will result in chamber concentrations in close proximity to the target concentration. If an exact concentration is essential, parameters may be individually adjusted to converge on the target concentration. PMID- 2220568 TI - Evaluation of methods for destruction of some alkylating agents. AB - Destruction procedures for dimethylsulfate (DMS), diethylsulfate (DES), methyl methanesulfonate (MMS), and ethyl methanesulfonate (EMS) have been investigated using treatment by 1 N NaOH, 1 N NH4OH, 1 M Na2CO3, and 1 M Na2S2O3. During the kinetic study of the destruction process, the determination of remaining concentrations of the alkylating agents was performed by the derivatization of p nitrophenoxide to p-nitroanisole and p-nitrophenetole, which were separated by high performance liquid chromatography. The mutagenic activity of the destruction products was evaluated by the Ames test using Salmonella tester strains TA97, TA98, TA100, and TA102. The kinetics of destruction in every case followed a time dependent exponential relationship. Solutions of 1 M Na2S2O3 showed the highest capacity for destruction of the four alkylating agents, half-lives of DMS, DES, MMS, and EMS being 0.14 min, 1.26 min, 0.60 min, and 5.26 min, respectively. No mutagenic activity was detected following complete destruction in 1 M Na2S2O3. PMID- 2220569 TI - Vibration exposure for selected power hand tools used in automobile assembly. AB - A practical method for assessing vibration exposure for workers operating vibrating hand tools on an automobile assembly line is presented. Vibration exposure is difficult to assess directly using many fast Fourier transform (FFT) spectral analyzers because of long task cycle times. Exposure time cannot be accurately estimated using time standards because of the high variability between operators and work methods. Furthermore, because workers frequently move about and get into inaccessible spaces, it is difficult to record vibration without interfering with the operation. A work sampling method was used for determining vibration exposure time by attaching accelerometers to the tools and suspending a battery-operated digital data logger from the air hose. Vibration acceleration and frequency spectra for each tool were obtained off-line replicating actual working conditions and analyzed together with exposure time data for determining individual worker vibration exposure. Eight pneumatic vibrating power hand tools, representing tools commonly used in an automobile assembly plant, were studied. Spectra for the rotary and reciprocating power tools and had large distinct dominant fundamental frequencies occurring in a narrow frequency range between 35 Hz and 150 Hz. These frequencies corresponded closely to tool free-running speeds, suggesting that major spectral component frequencies may be predicted on the basis of speed for some tools. PMID- 2220570 TI - Occupational intake by dermal exposure to polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in pulp mill industry. AB - The extent of probable intake of polychlorinated dibenzo-p-dioxins (dioxins) and polychlorinated dibenzofurans (furans) from exposure to process liquor, effluent, sludge, and pulp contaminated with dioxins/furans in pulp mills was examined. It is expected that intake of dioxins/furans by skin exposure may exceed their intake by inhalation. Limiting skin exposure to these chemicals should receive similar emphasis as inhalation exposure to volatile chemicals. Because of an inadequate scientific data base, assumptions erring toward safety had to be made in estimating the intake from potential exposures. Therefore, the calculated intakes are likely to be overestimates. PMID- 2220571 TI - Frequency of low-grade residual coronary stenosis after thrombolysis during acute myocardial infarction. AB - The clinical, angiographic and demographic characteristics of 42 patients with low-grade (less than 50%) residual stenosis at the infarct lesion after thrombolysis for acute myocardial infarction (MI) were assessed. The study group (group I) represented 21% of 198 consecutive patients receiving thrombolytic therapy over a 59-month period. Data on the 156 remaining patients were pooled for comparison (group II). Group I patients were predominantly men (86%) who were cigarette smokers (81%). Group II patients were predominantly men (75%, p greater than 0.10) but were significantly older (52 +/- 12 vs 56 +/- 10 years, p = 0.02). Prior acute MI or angina was unusual in group I. Sixty percent had no significant (greater than 50%) residual coronary artery disease while 25% had residual single artery disease. Average significant (greater than 50% diameter stenosis) residual vessel disease was 0.6 +/- 1.0 for group I and 1.9 +/- 0.9 for group II (p less than 0.001). In group I, average residual infarct lesion diameter stenosis was 36 +/- 7% in the right anterior oblique and 34 +/- 8% in the left anterior oblique views. Thirty-nine group I patients were discharged with medical therapy and 100% follow-up was obtained over a mean interval of 18 +/- 17 months. Fifteen patients experienced chest pain after acute MI accounting for 17 discrete events. Fifty nine percent of group I had a benign course on follow-up. Eight events were classified as unstable angina, 4 as acute MI and 5 as atypical angina. Documented coronary vasospasm occurred in 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220572 TI - Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II--DAVIT II) AB - The effect of verapamil on death and major events (i.e., death or reinfarction) after an acute myocardial infarction was studied in a double-blind, randomized, placebo-controlled multicenter trial. Eight hundred seventy-eight patients started treatment with verapamil, 360 mg/day, and 897 patients with placebo. Treatment started in the second week after admission and continued for up to 18 months (mean 16 months). Ninety-five deaths and 146 major events occurred in the verapamil group and 119 deaths and 180 major events in the placebo group. The 18 month mortality rates were 11.1 and 13.8% (p = 0.11, hazard ratio, 0.80; 95% confidence limits, 0.61 to 1.05), and major event rates 18.0 and 21.6% (p = 0.03, hazard ratio, 0.80; 95% confidence limits, 0.64 to 0.99) in the verapamil and placebo groups, respectively. In patients without heart failure in the coronary care unit the mortality rates were 7.7% in the verapamil group and 11.8% in the placebo group (p = 0.02, hazard ratio, 0.64; 95% confidence limits, 0.44 to 0.94), and major event rates 14.6 and 19.7% (p = 0.01, hazard ratio 0.70; 95% confidence limits (0.52 to 0.93). In patients with heart failure the mortality rates were 17.9 and 17.5% (p = 0.79, hazard ratio, 1.05; 95% confidence limits, 0.72 to 1.54), and major event rates 24.9 and 24.9% (p = 1.0, hazard ratio 0.98; 95% confidence limits 0.72 to 1.39). Long-term treatment with verapamil after an acute myocardial infarction caused a significant reduction in major events, and the positive effect was found in patients without heart failure. PMID- 2220573 TI - Impact of field-transmitted electrocardiography on time to in-hospital thrombolytic therapy in acute myocardial infarction. AB - To assess the impact of a field-transmitted electrocardiogram (ECG) on patients with possible acute myocardial infarction, randomized and open trials were performed with a portable electrocardiographic system coupled with a cellular phone programmed to automatically transmit ECGs to the base hospital. Consecutive patients served by the 6 units of the Salt Lake City Emergency Rescue System were studied; 71 patients were randomized to in-field ECG (n = 34) versus no ECG (n = 37). Time on scene was 16.4 +/- 9.7 minutes for the ECG group versus 16.1 +/- 7.0 minutes for the non ECG group (difference not significant). Time of transport averaged 18.2 +/- 9.9 and 17.6 +/- 13.1 minutes, respectively (difference not significant). Six of 34 patients with in-field ECG showed acute myocardial infarction, qualified for and received thrombolytic therapy at 48 +/- 12 minutes after hospital arrival (range 30 to 60) compared with 103 +/- 44 minutes (p less than 0.01) for 51 historical control patients and 68 +/- 29 minutes for 6 concurrent control patients without in-field ECG. Thus, in-field ECG causes negligible delays in paramedic time, leads to significant decreases in time to in hospital thrombolysis and may make in-field therapy feasible. In-field ECG may be an important addition to reperfusion strategies. PMID- 2220574 TI - Sensitivity of a set of myocardial infarction screening criteria in patients with anatomically documented single and multiple infarcts. AB - A subset of 3 screening criteria (Q wave greater than or equal to 30 ms in lead aVF, any Q or R wave less than or equal to 10 ms and less than or equal to 0.1 mV in lead V2, and R wave greater than or equal to 40 ms in V1) has been proposed to identify single nonacute myocardial infarcts. Cumulatively, these 3 criteria achieved 95% specificity, and 84 and 77% sensitivities for inferior and anterior myocardial infarcts, respectively, among patients identified by coronary angiography and left ventriculography. This study establishes the true sensitivities of the set of screening criteria in 71 patients with anatomically proven single myocardial infarcts and 32 patients with multiple myocardial infarcts. In the single inferior infarct group, the aVF criterion was 90% sensitive. The V2 criterion (any Q or R wave less than or equal to 10 ms and less than or equal to 0.1 mV) was 67% sensitive in the single anterior infarct group. No single criterion proved sensitive in identifying a posterolateral infarct. The set of screening criteria performed just as well for multiple infarcts as it did for single infarcts, with a cumulative sensitivity of 72%. The overall sensitivity of the screening set in the 103 patients in all groups was 71%. PMID- 2220575 TI - Two-year outcome after angiographically documented myocardial reperfusion for acute coronary occlusion. Thrombolysis and Angioplasty Study Group. AB - Reperfusion therapy has been clearly shown to decrease the early mortality after acute myocardial infarction, but the impact of this therapy on long-term survival has been less extensively evaluated. This study reports the extended follow-up of a large cohort of 810 patients treated with intravenous thrombolytic therapy combined, when considered necessary to maintain or augment infarct vessel patency, with mechanical reperfusion therapies. Each patient underwent coronary angiography within 2 hours of the initiation of the thrombolytic infusion. Coronary angioplasty was performed in 62% of the patients before hospital discharge and 21% underwent coronary artery bypass graft surgery. Follow-up was obtained in 96% to a mean of 18.8 months (range, 1.5 to 48 months). All-cause mortality over this period was 3.3%; 2.1% died from cardiac causes. Nonfatal reinfarction occurred in 5.1%. Although the low event rate limits the validity of statistical comparisons, the patients who survived the follow-up period tended to be younger (56 +/- 10 vs 65 +/- 7 years), to have better predischarge left ventricular function (left ventricular ejection fraction, 52 +/- 11 vs 46 +/- 13%) and to have a lower prevalence of multivessel coronary artery disease (45 vs 67%). This excellent long-term survival may, in part, reflect the exclusion of high-risk patients from enrollment in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) studies. It may also be attributable, however, to the frequent use of combined thrombolysis and mechanical revascularization in this population. PMID- 2220576 TI - Functional significance of myocardial perfusion defects induced by dipyridamole using thallium-201 single-photon emission computed tomography and two-dimensional echocardiography. AB - The mechanisms responsible for inhomogeneous myocardial blood flow after oral administration of a large dose (300 mg) of dipyridamole were assessed in 27 patients with serial thallium-201 single-photon emission computed tomography (SPECT) and simultaneous 2-dimensional echocardiograms. Myocardial tomographic images were obtained 50 minutes and 3 to 4 hours after administration of dipyridamole. Two-dimensional echocardiograms were recorded at baseline and then every 15 minutes for 60 minutes. Dipyridamole caused only a mild reduction in blood pressure (from 129 +/- 18 to 126 +/- 16 mm Hg) and a mild increase in heart rate (from 69 +/- 15 to 73 +/- 4 beats/min). Sixteen patients had perfusion defects after dipyridamole by SPECT, which underwent partial or total filling-in. Fourteen of these patients (87.5%) had either a new abnormality or further deterioration of a preexisting wall motion abnormality by 2-dimensional echocardiography, and thus were considered to have developed transient ischemia during dipyridamole administration. Ten of 11 patients (91%) with normal perfusion or fixed defects by SPECT had no further deterioration in wall motion after oral dipyridamole, and were thus considered to have no evidence of myocardial ischemia. In conclusion, most patients with transient thallium-201 defects after dipyridamole develop transient worsening of resting wall motion by 2-dimensional echocardiography, suggestive of true myocardial ischemia. Because myocardial oxygen demand, as indicated by the heart rate-blood pressure product, did not change significantly, the mechanism of myocardial ischemia in these patients is likely to be diminished regional blood flow related to a "subendocardial steal" induced by dipyridamole. PMID- 2220577 TI - Left ventricular dilatation and pulmonary thallium uptake after single-photon emission computer tomography using thallium-201 during adenosine-induced coronary hyperemia. AB - This study examined the implications of left ventricular (LV) dilatation and increased pulmonary thallium uptake during adenosine-induced coronary hyperemia. The lung-to-heart thallium ratio in the initial images was significantly higher in patients with coronary artery disease (CAD) than normal subjects; 0.48 +/- 0.16 in 3-vessel disease (n = 16), 0.43 +/- 0.10 in 2-vessel disease (n = 20), 0.43 +/- 0.08 in 1-vessel disease (n = 16) and 0.36 +/- 0.05 in normal subjects (n = 7) (p less than 0.001, 0.09 and 0.06, respectively). There was a significant correlation between the severity and the extent of the perfusion abnormality (determined from the polar maps) and the lung-to-heart thallium ratio (r = 0.51 and 0.52, respectively, p less than 0.0002). There was also a significant correlation between lung thallium washout and lung-to-heart thallium ratio (r = 0.42, p = 0.0009) and peak heart rate (r = -0.49, p less than 0.0001). The LV dilatation was mostly due to an increase in cavity dimension (30% increase) and to a lesser extent (6% increase) due to increase in LV size. (The cavity dimensions were measured from the short-axis slices at the midventricular level in the initial and delayed images). The dilation was seen in patients with CAD but not in the normal subjects. These changes correlated with the extent and severity of the thallium perfusion abnormality. Thus, adenosine-induced coronary hyperemia may cause LV dilation and increased lung thallium uptake on the basis of subendocardial ischemia. PMID- 2220578 TI - Effects of bepridil and diltiazem on ventricular repolarization in angina pectoris. AB - To examine the time-course and potential predictors of prolongation of ventricular repolarization with the calcium antagonist bepridil, the effects of bepridil (300 to 500 mg/day; n = 45) and diltiazem (180 to 300 mg/day; n = 42) on QT and QTc interval duration were analyzed in a randomized double-blind study in patients with angina pectoris. Electrocardiograms were recorded before and 14, 28, 70 and 112 days after treatment was begun. After 14 days, bepridil prolonged QT interval by 26 +/- 35 ms (range, -60 to 120 ms) and QTc (Bazett's formula) by 17 +/- 33 ms (range, -73 to 107 ms) compared to baseline (both p less than 0.05). QT or QTc did not significantly increase thereafter. However, among the 30 patients who had less than 40 ms QTc prolongation at day 14 compared with baseline, 13 (43%) exceeded this limit on at least 1 of the following visits. Diltiazem did not significantly alter QT or QTc intervals. The absolute change in QTc interval from baseline observed after 14 days of bepridil therapy was inversely proportional to the baseline QTc interval (r = -0.68; n = 42; p less than 0.001). The degree of bepridil-induced QTc prolongation on day 14 correlated with pretreatment RR interval (r = 0.36; n = 42; p less than 0.02). In conclusion, chronic administration of bepridil but not of diltiazem prolongs ventricular repolarization in patients with angina pectoris. The overall effects of bepridil therapy on QT and QTc intervals can be assessed by an electrocardiogram recorded after 14 days of treatment but subsequent measurements may be required in individual patients. A short baseline QTc interval and a slow initial heart rate may be potentially useful predictors of a greater QTc prolongation with bepridil. PMID- 2220579 TI - Effects of intravenous verapamil on left ventricular relaxation and filling in stable angina pectoris. AB - Left ventricular (LV) diastolic function is often impaired in coronary artery disease (CAD). To assess whether verapamil could improve LV diastolic properties, 12 patients with CAD undergoing right- and left-sided cardiac catheterization, as well as simultaneous radionuclide angiography, were studied before and during intravenous administration of verapamil (0.1 mg/kg as a bolus followed by 0.007 mg/kg/min). The heart rate was kept constant by atrial pacing in both studies. LV pressure-volume relations were obtained. Verapamil decreased LV systolic pressure (130 +/- 22 to 117 +/- 16 mm Hg, p less than 0.01) and the end-systolic pressure/volume ratio (2.4 +/- 1.3 to 1.6 +/- 0.5 mm Hg/ml, p less than 0.05), and increased LV end-diastolic (13 +/- 4 to 16 +/- 4 mm Hg, p less than 0.02) and pulmonary capillary pressures (10 +/- 5 to 12 +/- 5 mm Hg, p less than 0.005). Despite such negative inotropic effects, cardiac index increased (3.4 +/- 0.7 to 3.9 +/- 0.6 liters/min/m2, p less than 0.02). The time constant of isovolumic relaxation shortened (63 +/- 14 to 47 +/- 9 ms, p less than 0.02); peak filling rate increased (370 +/- 155 to 519 +/- 184 ml/s, p less than 0.001; 2.6 +/- 1.1 to 3.3 +/- 0.9 end-diastolic counts/s, p less than 0.02; and 4.1 +/- 1.6 to 5.5 +/- 1.5 stroke counts/s, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220581 TI - Long-term follow-up in patients with incessant ventricular tachycardia. AB - Seventeen patients with coronary artery disease, idiopathic dilated cardiomyopathy or no organic heart disease who presented with incessant ventricular tachycardia (VT) were studied and followed for a mean period of 51 +/ 35 months. In these patients the incessant VT included greater than or equal to 3 episodes of sustained VT at a rate of greater than or equal to 120 beats/min and frequent episodes of nonsustained VT over a 24-hour period. No patient had electrolyte disorder, prolonged QT interval, drug-induced arrhythmia or myocardial infarction less than 2 weeks old. Six patients died within 27 months of follow-up; 4 from sudden death and 2 from acute myocardial infarction. Three of the 11 surviving patients had remission of their VT within 1 week after the diagnosis of incessant VT. In 3 other patients in whom antiarrhythmic drugs were discontinued during follow-up because of adverse effects of the drugs or other medical reasons, 2 were found in remission. In the remaining 5 alive patients, deliberate attempts were made to discontinue the antiarrhythmic drugs; 4 of these patients were found in remission when the drugs were discontinued. Thus, 9 of these patients (53%) with incessant VT had remission over a mean follow-up of 55 +/- 34 months after discontinuation of the antiarrhythmic drugs. The probability of remission in patients surviving incessant VT warrants trials of discontinuation of antiarrhythmic drugs in these patients. PMID- 2220580 TI - Analysis of programmed stimulation methods in the evaluation of ventricular arrhythmias in patients 20 years old and younger. AB - The purpose of this study was to systematically evaluate programmed ventricular stimulation in patients less than 21 years of age undergoing electrophysiologic testing. A standardized protocol was applied in 55 consecutive patients (mean age 14 years) with the following clinical presentations: sustained ventricular tachycardia (VT) (n = 17); ventricular fibrillation (VF) (n = 7); syncope with heart disease (n = 10); nonsustained VT (n = 6); and syncope with an ostensibly normal heart (n = 15). The stimulation protocol consisted of 1 and 2 ventricular extrastimuli during sinus rhythm, followed by 1 to 4 (S2, S3, S4, S5) extrastimuli during pacing at 2 ventricular sites. Of the 17 patients with sustained VT, 12 had induction of the arrhythmia (sensitivity = 71%). Overall, 18 of 55 patients had inducible sustained VT, with this response significantly enhanced by use of S4 or S5 protocols (p = 0.02). Although no syncope patients with an ostensibly normal heart had inducible sustained VT, 7 had polymorphic nonsustained VT in response to ventricular stimulation. The mean number of extra stimuli preceding the induction of nonsustained or sustained VT or VF did not differ. The induction of VF in 5 cases during this study was preceded in each case by extrastimuli intervals less than or equal to 190 ms. Thus, data indicate that aggressive stimulation protocols appear to be required for induction of sustained VT in most young patients, nonsustained polymorphic VT as a response to aggressive programmed stimulation is of uncertain significance, and that coupling intervals less than or equal to 190 ms may correlate with the induction of VF. PMID- 2220582 TI - The nuclear pacemaker: is renewed interest warranted? AB - From 1973 through 1987, 155 radioisotope-powered "nuclear" pacemakers were implanted in 132 patients at the Newark Beth Israel Medical Center. The longevity of the first 15 devices, all of which were fixed-rate (VOO) pacemakers, was significantly better than that of 15 lithium-chemistry demand (VVI) pacemakers used as control devices (p = 0.0002). Of the entire cohort of 155 nuclear pacemakers, 136 were VVI devices and 19 were VOO units. The patients with VOO pacemakers needed reoperations more often than did those with VVI pacemakers, chiefly for mode change (p less than 0.001). Power-source failure was observed in only 1 case, but 47 nuclear pacemakers were removed for other reasons, including component malfunction (15 units), mode change (12 units), high pacing thresholds (8 units) and lead or connector problems (5 units). The actuarial survival at 15 years was 99% for power sources and 82% for the entire pacing systems (pulse generators plus leads). The frequency of malignancy was similar to that of the population at large and primary tumor sites were randomly distributed. Deaths most commonly were due to cardiac causes (68%). Thus, nuclear pacemakers are safe and reliable and their greater initial cost appears to be offset by their longevity and the resulting decrease in the frequency of reoperations. It is reasonable to suggest that further use be made of long-lasting nuclear power sources for modern pacemakers and other implantable rhythm-management devices. PMID- 2220583 TI - Effects of metoprolol on rest and exercise cardiac function and plasma catecholamines in chronic congestive heart failure secondary to ischemic or idiopathic cardiomyopathy. AB - To define the effects of 2 months of metoprolol therapy on cardiac function, aerobic performance and sympathetic nervous system activity, metoprolol (75 to 100 mg/day) was administered to 10 patients with chronic congestive heart failure (CHF). Metoprolol was discontinued in 2 patients because of worsening CHF. In the remaining 8 patients, peak oxygen uptake increased significantly (14.8 +/- 3.0 to 16.1 +/- 2.5 ml/kg/min, p less than 0.05) as did the oxygen pulse (9.0 +/- 2.2 to 12.6 +/- 1.8 ml/beat, p less than 0.02). Resting heart rate (87 +/- 18 to 62 +/- 9 beats/min, p less than 0.05) and peak exercise heart rate (133 +/- 13 to 105 +/ 30 beats/min, p less than 0.02) were both reduced. Mean resting ejection fraction increased from 0.15 +/- 0.06 to 0.25 +/- 0.11 and peak exercise ejection fraction also tended to increase (0.19 +/- 0.11 to 0.28 +/- 0.15, difference not significant). Both resting plasma norepinephrine (613 +/- 706 to 303 +/- 142 pg/ml, p less than 0.05) and epinephrine (71 +/- 50 to 40 +/- 21 pg/ml, p less than 0.05) were reduced. Circulating lymphocyte beta-adrenergic receptor number was unchanged (1,334 +/- 292 to 1,344 +/- 456 receptors/cell, difference not significant). It is concluded that metoprolol therapy is associated with improvements in rest and exercise ventricular performance and maximal aerobic capacity. These improvements are associated with a decline in resting sympathetic nervous system activity. PMID- 2220584 TI - Digital acoustical analysis of normal and bimodal Bjork-Shiley 60 degrees convexo concave heart valves. AB - Fracture of the outlet strut of the Bjork-Shiley 60 degrees convexo-concave (BS60CC) valve has been attributed to a bimodal closing pattern in certain valves in which the closing disk rotates about the inlet strut, causing upward displacement of the outlet strut and its eventual fracture. This article reports the in vivo studies of the normal BS60CC valve and the in vitro studies of the normal and bimodal BS60CC valves, using a digital acoustical signal processing technique, in which the individual collisions (impact history) of the occluder disk with the components of the valve body are revealed during each closing cycle. In vitro analysis of the closing acoustical signals of normal BS60CC valves showed impact history cluster width (IHCW) means of 2.07 +/- 0.85 ms (standard error), not significantly different from those of 1.86 +/- 0.58 ms (standard error) observed in 38 clinically normal patients with BS60CC valves (p greater than 0.1). The bimodal valves showed IHCW of 6.14 +/- 0.98 ms (standard error), in vitro, which was significantly greater than those observed in the normal in vitro valve group and in the normal patient population (p less than 0.0001). PMID- 2220585 TI - "Cardioprotection"--not all calcium antagonists are created equal. PMID- 2220586 TI - Percutaneous transluminal coronary angioplasty in octogenarians with unstable coronary syndromes. PMID- 2220587 TI - Frequency and causes of failure with contemporary balloon coronary angioplasty and implications for new technologies. PMID- 2220588 TI - Creatine kinase-MB activity after implantation of a cardiac pacemaker. PMID- 2220589 TI - From various kinds of heart rate variability to chronocardiology. PMID- 2220590 TI - Prognosis and predisposing factors for essential malignant hypertension in predominantly black patients. PMID- 2220591 TI - Transesophageal color flow Doppler and echocardiographic features of normal and regurgitant St. Jude Medical prostheses in the mitral valve position. PMID- 2220592 TI - Transesophageal color flow Doppler and echocardiographic features of normal and regurgitant St. Jude Medical prostheses in the aortic valve position. PMID- 2220593 TI - Comparison of clinical features in patients greater than or equal to 60 years of age to those less than or equal to 40 years of age with hypertrophic cardiomyopathy. PMID- 2220594 TI - Obstruction of systemic pulmonary arterial shunts by diagnostic cardiac catheters. PMID- 2220595 TI - Nongeometric Doppler stroke volume determination is limited by aortic size. PMID- 2220596 TI - Quantification of tricuspid regurgitation by Doppler color flow mapping after cardiac transplantation. PMID- 2220597 TI - Ventricular tachycardia and torsades de pointes complicating pentamidine therapy of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. PMID- 2220598 TI - Primary sarcoma of the heart causing mitral stenosis. PMID- 2220599 TI - We think we are one, we act as if we are one, but we are not one. PMID- 2220601 TI - Mechanisms in heart failure and the role of angiotensin-converting enzyme inhibition. AB - The four major diagnostic criteria for the syndrome of congestive heart failure are left ventricular dysfunction, exercise intolerance, pulmonary congestion or edema and ventricular arrhythmias. Activation of norepinephrine, angiotensin II, vasopressin and atrial natriuretic peptide may be a key factor in the vasoconstriction and increased impedance to left ventricular ejection in heart failure. Interventions that interfere with these vasoconstrictor mechanisms should have a salutary effect on left ventricular performance. Treatment with angiotensin-converting enzyme (ACE) inhibitors, alpha-adrenoceptor blockers and vasopressin antagonists has resulted in hemodynamic benefits, but it has been more difficult to demonstrate long-term clinical effectiveness. Reductions in mortality have been demonstrated in patients with heart failure treated with vasodilators and ACE inhibitors. Improvement in the quality of life and prolongation of life are the only two appropriate goals in the management of heart failure. Further understanding of the role of angiotensin II and its interference by ACE inhibition in the tissue processes of heart failure is needed. PMID- 2220600 TI - Renal effects of angiotensin-converting enzyme inhibition in congestive heart failure. AB - Some studies report that inhibition of angiotensin-converting enzyme (ACE) improves renal function in patients with congestive heart failure, whereas others report that renal deterioration is a frequent complication of treatment with ACE inhibitors. This article explores the mechanisms by which antagonism of the renin angiotensin system improves kidney function in some patients while causing harm in others. ACE inhibition may alter renal blood flow, glomerular perfusion pressure, basement membrane activity and renal tubular function both directly and indirectly. In most patients, renal function is maintained as other neurohormonal mechanisms compensate for the negative effects and permit the positive effects (such as improved renal flow) to predominate. However, when physiologic characteristics or iatrogenic interventions (such as volume reduction or prostaglandin inhibition) limit the effectiveness of neurohormonal compensation to maintain renal autoregulation, clinically important deterioration in renal function may occur. An understanding of the renal effects of ACE inhibitors permits their safe and effective use in most patients with congestive heart failure. PMID- 2220602 TI - Potential role of the tissue renin-angiotensin system in the pathophysiology of congestive heart failure. AB - The circulating renin-angiotensin system (RAS) plays an important role in the maintenance of cardiovascular homeostasis. It has recently been demonstrated that endogenous RAS exist in target tissues that are important in cardiovascular regulation. This article reviews the multiple effects of angiotensin II in target tissues, the evidence for the presence of functional tissue RAS and the data that suggest a role for these tissue RAS in the pathophysiology of heart failure. Activation of circulating neurohormones is predictive of worsened survival in heart failure; however, cardiac and renal tissue RAS activities are also increased in the compensated stage of heart failure, when plasma renin angiotensin activity is normal. It is hypothesized that the plasma RAS maintains circulatory homeostasis during acute cardiac decompensation, while changes in tissue RAS contribute to homeostatic responses during chronic sustained cardiac impairment. This concept of different functions of circulating and tissue RAS in the pathophysiology of heart failure may have important pharmacologic implications. PMID- 2220603 TI - Neuroendocrine activity in congestive heart failure. AB - The increased neuroendocrine activity in patients with congestive heart failure appears to be a generalized attempt to maintain blood pressure at the expense of reduced cardiac performance and salt and water retention. It is likely that baroreceptor dysfunction contributes to increased sympathetic nervous system activity in patients with congestive heart failure. The usual tonic inhibitory messages emanating from baro- and mechanoreceptors in the great vessels and heart fail to adjust sympathetic traffic from the brain to the periphery, leading to uninhibited sympathetic tone. Arginine vasopressin and plasma renin activity may be increased secondarily; however, plasma renin activity activation could also be induced by a low-salt diet and diuretic use. Preliminary baseline data indicate that patients with left ventricular dysfunction (ejection fraction less than or equal to 35%) but no or very mild symptoms of heart failure have increased plasma levels of norepinephrine, atrial natriuretic factor and arginine vasopressin, while plasma renin activity is normal, suggesting that neuroendocrine activity contributes to the pathogenesis of congestive heart failure. Neurohormones such as angiotensin II may alter gene expression, leading to changes in the shape and size of the cell. Remodeling of the heart and blood vessels is associated with both heart failure and hypertension. Angiotensin-converting enzyme inhibitors have been demonstrated to retard or reverse the remodeling process under certain experimental conditions. Studies are currently under way to test this possibility in patients. PMID- 2220604 TI - Effects of enalapril and neuroendocrine activation on prognosis in severe congestive heart failure (follow-up of the CONSENSUS trial). CONSENSUS Trial Study Group. AB - This study enrolled 253 patients with severe heart failure (New York Heart Association functional class IV) from 35 centers in Scandinavia, randomly assigned to treatment with placebo or enalapril, in addition to their usual treatment for heart failure. After an initial titration period, the daily doses of enalapril ranged from 2.5 to 40 mg. At the end of the trial, 46% of the placebo-treated patients and 61% of the enalapril-treated patients were alive (p = 0.003); the survival figures at 8 months after completion of the trial were 32 and 48%, respectively (p = 0.001); and 21 and 30%, respectively (p = 0.006) at the 2-year follow-up. In the placebo group, there was a significant positive association between mortality and baseline levels of norepinephrine, epinephrine, angiotensin II, aldosterone and atrial natriuretic peptide; no such association was found in the enalapril-treated patients. The results suggest that the effects of enalapril on mortality are related to a counteraction of the neuroendocrine activation in general and to the renin-angiotensin system in particular. PMID- 2220605 TI - Pharmacology of angiotensin-converting enzyme inhibitors as a guide to their use in congestive heart failure. AB - The pharmacokinetics of the angiotensin-converting enzyme (ACE) inhibitors are difficult to assess for several reasons. First, these compounds exert their influence by inhibiting an intermediary enzyme of a cascade of enzymatic events, whose rate-limiting enzyme (renin) is not directly affected by ACE inhibition. Second, renin and angiotensin I accumulate during ACE inhibition and a change in the dose of an ACE inhibitor could produce sudden shifts of angiotensin I to angiotensin II. Third, components of the circulating renin system require the interaction of several organ systems and effector sites. Fourth, the kinetics of ACE inhibitors can be influenced by the organ systems responsible for drug absorption, metabolism and excretion, and the functional status of these systems can be affected by the heart failure process. Fifth, at least some portion of the cardiovascular effects of ACE inhibitors is influenced by the contributions of other systems whose physiologic effects may be of importance in some patients with congestive heart failure. Sixth, the potential impact of tissue-bound ACE is not yet fully understood. Finally, for appropriate drug dosing, the effects of aging on the heart failure process, the extent of renin system activity, and the disposition of ACE inhibitors need to be considered. Because of their complex pharmacokinetics, treatment with ACE inhibitors has been guided by their pharmacodynamic and clinical characteristics. PMID- 2220606 TI - Clinical and hemodynamic assessment of the hepatojugular reflux. AB - The hepatojugular reflux (HJR) test was studied to assess the ability to clinically predict response during cardiac catheterization and to determine its significance in patients without heart failure and correlate it to their baseline hemodynamic parameters. Sixty-five patients considered to be free of heart failure undergoing routine cardiac catheterization were enrolled. The HJR test, defined as the venous pressure response to sustained abdominal compression, was performed in a standardized manner at the bedside assessing change in internal jugular venous pressure and during right-sided cardiac catheterization measuring change in right atrial pressure. For comparison a sustained increase greater than or equal to 1 cm was considered positive. In 62 of 65 patients the HJR test stabilized by 15 seconds. The results during examination at the bedside agreed with those at catheterization (K = 0.74, p less than 0.001). The HJR test result correlated best with baseline mean right atrial pressure (r = 0.59) and right ventricular end-diastolic pressure (r = 0.51), and in bivariate regression analysis predicted right atrial (F(1,63) = 32.8, R2 = 0.34, p less than 0.0001) and right ventricular end-diastolic (F(1,63) = 22, R2 = 0.26, p less than 0.0001) pressures. A positive test had high sensitivity and specificity for predicting right atrial pressure greater than 9 mm Hg (1.0, 0.85) and right ventricular end diastolic pressure greater than 12 mm Hg (0.90, 0.89). It is concluded that 15 seconds is adequate for interpretation, and bedside observation predicts the response during right-sided cardiac catheterization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220607 TI - Anatomic correlations of the long-axis views in biplane transesophageal echocardiography. AB - The number of views obtainable during transesophageal echocardiography (TE) has been limited by the fixed position of the transducer at the end of the probe. This has confined standard TE studies to short-axis tomography of the heart and aorta. Recently, a biplane TE probe has become available that is capable of both long- and short-axis imaging. This study prospectively assessed the application of the long-axis plane of the biplane probe in providing complementary long-axis views in ambulatory patients. Six standard long-axis views could be obtained and were compared with corresponding anatomic sections to illustrate anatomic relations and facilitate structure identification. The long-axis views provide a better appreciation of the 3-dimensional nature of cardiac anatomy and function, especially in demonstrating the relation of vertically aligned structures. PMID- 2220608 TI - Circadian fluctuations in ventricular response to atrial fibrillation. PMID- 2220609 TI - Comparison of indications for aortic valve replacement in 1978 and in 1988. PMID- 2220611 TI - Assessing left ventricular ejection force. PMID- 2220610 TI - Noninvasive evaluation of left ventricular performance with a new systolic time interval, the Q-V peak, and comparison with established systolic time intervals. PMID- 2220613 TI - Functional status after coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. AB - Two cohorts of consecutive patients of comparable age with similar preprocedure cardiac function who underwent either coronary artery bypass grafting (CABG; n = 106) or percutaneous transluminal coronary angioplasty (PTCA; n = 64) were entered into a prospective comparison study examining functional status and return to work during the first year of recovery. Patients were evaluated using standardized functional status instruments for activities of daily living, work performance, social activity, mental health and quality of social interaction at 1, 6 and 12 months after the procedure. Within the CABG group, statistically significant improvements of functional status on every subscale were noted over the 1-year follow-up. Patients undergoing PTCA demonstrated significant improvement in all dimensions except for the quality of interaction at 1 year as compared with baseline. When the 2 groups were compared, the PTCA group demonstrated greater participation than the CABG group in routine daily physical and social activities at 1 and 6 months, but this apparent advantage disappeared by 1 year. Measures of psychological functioning were better after CABG than after PTCA. A reduction in the number of those with employment occurred in both the CABG and PTCA groups, independent of physical functional status measures, which improved in both groups after the procedures. For those with employment, the CABG group reported the greatest improvement in work performance. PMID- 2220612 TI - Transient left ventricular filling abnormalities (diastolic stunning) after acute myocardial infarction. AB - A variety of experimental studies suggest that diastolic left ventricular (LV) function changes after acute myocardial infarction (AMI), but limited data exist on these changes in humans. To assess diastolic filling after AMI, 60 patients underwent Doppler echocardiographic examination within 24 hours of AMI. Of 54 patients who also underwent catheterization, 45 (83%) were successfully reperfused. A subgroup of 17 patients underwent a follow-up Doppler examination at 7 days after infarction, whereas 15 patients with stable exertional angina served as control subjects. There was no significant difference in age, gender, incidence of systemic hypertension or diabetes mellitus, heart rate, mean arterial pressure or severity of coronary artery disease between the infarct and control groups. The infarct group had a lower velocity time integral total (9.9 +/- 0.4 cm vs 12.0 +/- 0.9 cm, p less than 0.001), a lower velocity time integral E (5.8 +/- 0.3 cm vs 6.8 +/- 0.5 cm, p less than 0.01) and a lower velocity time integral 0.333 (3.5 +/- 0.4 cm vs 6.1 +/- 0.5 cm, p less than 0.01) than the control group. In addition, velocity time integral A/total was significantly greater in the infarction group (0.44 +/- 0.03 vs 0.35 +/- 0.04, p less than 0.01) compared to the control group. The follow-up subgroup showed an increase in velocity time integral total (p less than 0.01), velocity time integral E (p less than 0.05) and velocity time integral 0.333/total (p less than 0.05) over the first 7 days after infarction. The final recovery values at 7 days were not significantly different from those of the coronary artery disease group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220615 TI - Results of percutaneous transluminal coronary angioplasty of high-risk angulated stenoses. AB - Percutaneous transluminal coronary angioplasty (PTCA) of angulated stenoses has been found in studies using older PTCA equipment to be associated with a heightened risk of procedure-related major ischemic events. To better understand the factors associated with procedural risk and to identify means of lessening that risk, 100 patients, treated sequentially from 1986 to 1989, who underwent PTCA of stenoses located at greater than or equal to 45 degrees bends, were characterized for 27 clinical, anatomic and procedural variables. Clinical outcome of angioplasty was related to these variables. In addition, results from 344 consecutive contemporary patients undergoing PTCA of nonangulated lesions were compared to those of the study group. Procedural success was achieved in only 70% of patients with angulated stenoses, compared with 306 of 344 (89%) nonangulated stenoses, and major ischemic complications (death, bypass surgery or myocardial infarction) occurred in 13% of patients with angulated stenoses compared with 12 of 344 (3.5%) with nonangulated stenoses (both p less than 0.001). The presence of associated thrombus, stenosis length greater than 10 mm or age greater than or equal to 65 years led to an even higher risk of major complications (9 of 44 = 20.5%), whereas highly experienced angioplasty operators and the use of polyethylene terephthalate balloons appeared to decrease risk and increase the likelihood of success. PTCA of such stenoses should be undertaken only cautiously and in carefully selected patients. PMID- 2220614 TI - Patient-related variables and restenosis after percutaneous transluminal coronary angioplasty--a report from the M-HEART Group. AB - As part of a randomized prospective study designed to investigate the restenosis process after percutaneous transluminal coronary angioplasty (PTCA), the relation between patient-related variables and restenosis rate was examined. A total of 722 patients had successful PTCA. Angiographic follow-up was scheduled for 6 +/- 2 months after the procedure and achieved in 510 patients (71%), yielding 598 lesions for analysis. The overall restenosis rate was 40%. The rate was higher in patients undergoing early restudy for a clinical event than in those undergoing routinely scheduled follow-up restudy (71 vs 22%, p less than 0.0001). Age, sex, cigarette smoking history, diabetes mellitus and history of previous myocardial infarction were not associated with restenosis rate. Angina duration and severity before PTCA were also unrelated to restenosis rate. In summary, these variables, many of which have been previously implicated in restenosis, were not found to be predictors of restenosis. The decision to perform PTCA in individual patients should not be negatively influenced by the presence of these factors. PMID- 2220616 TI - Quantitative angiographic comparison of the immediate success of coronary angioplasty, coronary atherectomy and endoluminal stenting. AB - Coronary atherectomy and coronary stenting effectively reduce the severity of coronary artery stenoses, but direct comparisons of these interventions with conventional balloon angioplasty have not been performed. To compare the immediate efficacy of these 3 interventions, the angiographic morphology and the severity of the residual coronary stenosis were quantitatively evaluated in 18 patients undergoing coronary atherectomy and in 21 patients treated by endoluminal coronary stenting. Each of these groups of patients was compared with a matched group of coronary angioplasty patients selected from a large, computerized data-base. The variables matched included patient age and sex, lesions site and severity, and lesion complexity. Both coronary atherectomy and coronary stenting more effectively reduced the severity of the coronary stenosis when compared with balloon angioplasty. The luminal diameter stenosis was reduced from 69 +/- 10 to 22 +/- 20% in the atherectomy group compared with a reduction from 74 +/- 11 to 44 +/- 14% in the matched coronary angioplasty population (p = 0.008). Similarly, the luminal diameter stenosis was reduced from 77 +/- 11 to 26 +/- 12% in the stented group compared with a reduction from 81 +/- 10 to 42 +/- 14% in the matched coronary angioplasty group (p = 0.014). In addition, moderate or severe coronary dissections were noted more frequently in the coronary angioplasty groups than in their respective atherectomy and stent groups (0 vs 33%, p = 0.008, and 5 vs 19%, p = 0.15, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220617 TI - Early postoperative balloon coronary angioplasty for failed coronary artery bypass grafting. AB - In a small number of patients, coronary artery bypass grafting (CABG) fails to relieve anginal symptoms. The usefulness of coronary angioplasty for the treatment of early (less than or equal to 90 days) recurrent ischemia after CABG was examined. Forty-five patients were treated from 2 to 90 days after CABG, including 8 patients studied emergently for prolonged ischemic symptoms. One-, 2- and 3-vessel native disease was found in 4, 10 and 31 patients, respectively. At the time of postoperative angiography, the major anatomic mechanism of recurrent ischemia was complete vein graft occlusion in 12 patients (27%), internal mammary artery occlusion in 3 (7%), vein graft stenoses in 13 (29%), internal mammary artery stenoses in 10 (22%), unbypassed disease in 4 (8%) and disease distal to the graft insertion site in 3 (7%). Angioplasty was successful at 91 of 98 sites (93%), including 95% of 41 lesions in native arteries, 89% of 46 lesions in vein grafts and 100% of 11 internal mammary artery lesions attempted. Complete revascularization was achieved in 84% of patients. There were 2 in-hospital deaths and 2 myocardial infarctions. Two additional patients underwent repeat CABG before discharge after uncomplicated but unsuccessful angioplasty. At late follow-up of the 43 survivors (mean 44 months), there were 4 deaths, 2 of which were noncardiac. Repeat CABG was required in only 3 patients and repeat angioplasty was performed in 10. Angina was absent or minimal in 35 patients; 17 patients were employed full time. Thus, percutaneous transluminal coronary angioplasty can relieve myocardial ischemia after unsuccessful CABG in the majority of patients. PMID- 2220619 TI - Circadian rhythmicity of rate-normalized QT interval in hypothyroidism and its significance for development of class III antiarrhythmic agents. AB - Lengthening of repolarization and refractoriness occurs in hypothyroidism; it is associated with a reduced probability of arrhythmias, with the converse occurring in hyperthyroidism. Because the QT interval and its circadian rhythmicity relative to heart rate is poorly defined in man, we used our new computer assisted technique to measure QT interval in our analysis of 24-hour Holter tapes before and after (8 to 12 weeks) thyroxine (T4) replacement in 10 patients with hypothyroidism; the findings were compared to those in 6 normal control subjects. QTc interval was prolonged (p less than 0.02) and heart rate decreased (p less than 0.005) during the hypothyroid state. Data were analyzed for circadian rhythmicity by repeated-measures analysis. Circadian variation in QTc and heart rate was statistically significant during hypothyroid and euthyroid states (p less than 0.001) as well as in control subjects, but the circadian rhythmicity of QTc interval and heart rate were out of phase; the maximum prolongation of QTc occurred between midnight and 6 A.M., at a time when heart was at its lowest. QTc interval remained significantly prolonged after 8 to 12 weeks of T4 replacement, when biochemical indexes of hypothyroidism had returned to normal values. The computer-assisted QTc interval determination technique that we used, and our data on the circadian rhythmicity of QTc and heart rate, have significant implications for the development of new class III antiarrhythmic agents. PMID- 2220618 TI - Role of alcohol in recurrences of atrial fibrillation in persons less than 65 years of age. AB - The role of alcohol in recurrences of atrial fibrillation (AF) was assessed in a consecutive series of 98 patients (75 men) aged less than 65 years. In addition to etiologic assessment using clinical and laboratory methods and echocardiography, the patients' drinking habits were evaluated by recording the amount of alcohol used during the week preceding AF, by responses to the CAGE (Cut, Annoying, Guilt, Eye; see below) questionnaire (a screening test for alcohol abuse) and by selected laboratory tests. Two groups of control subjects were studied: 98 sex- and age-matched patients admitted to the emergency ward for acute illnesses, and 50 subjects selected randomly from the local out-of-hospital population. The mean alcohol consumption among men during the study week was 186 g (median 45 g; range 0 to 2,100 g) among patients, whereas among male hospital and population control subjects it was 86 g (30 g; 0 to 1,050 g) and 94 g (35 g; 0 to 630 g), respectively. When the weekly alcohol consumption was analyzed in 3 categories (0; 1 to 210 g; greater than 210 g), there was a significant difference between AF cases and hospital control patients (p = 0.03), but not between AF cases and population control subjects. Multivariate analysis of data of AF cases and population control subjects showed that alcohol intake and a positive response to 1 or more of the CAGE questions were independently related to AF in men. Other independent risk factors were the presence of heart disease, low serum potassium and lack of sleep or experience of excess psychologic stress, or both.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220620 TI - Chronic transvenous pacemaker lead removal using a unique, sequential transvenous system. AB - Transvenous removal of 43 consecutive chronic pacemaker leads was successful in 28 patients. For leads not removed by traction at the pacemaker connection terminal, a unique locking stylet was advanced through the inner coil lumen and engaged at the tip to allow traction without lead elongation. Leads not extracted with the locking stylet alone had traction maintained on the stylet as sheaths were advanced over the lead to dilate and detach any fibrous tissue adherent to the lead. By applying traction at the pacemaker connection terminal, 2 leads were removed. The locking stylet alone extracted 9 leads. Both the locking stylet and sheaths were necessary to explant 32 leads. There were 15 right atrial and 22 right ventricular leads completely removed. Additionally, 6 right ventricular leads were subtotally removed leaving only the tip in the right ventricular apex. Avulsed myocardium was removed with the lead in 1 patient without sequelae. A subacute hemothorax developed in 1 patient 18 days after discharge requiring drainage, and subclavian vein thrombosis developed in another, which was successfully treated with anticoagulation. Hypotension occurred in 1 patient during final positioning of new leads, which responded to conservative treatment. Chronic pacemaker leads can be reliably removed without thoracotomy. Both a unique locking stylet to allow traction without lead elongation and a sheath to dilate and detach adherent fibrous tissue are needed for consistent success. Recognized complications included myocardial avulsion without sequelae, subacute hemothorax, subclavian vein thrombosis and transient hypotension. PMID- 2220621 TI - Comparison of the antihypertensive efficiency of nitrendipine, metoprolol, mepindolol and enalapril using ambulatory 24-hour blood pressure monitoring. AB - In a randomized 6-month study of 201 patients, the antihypertensive efficiency of the calcium antagonist nitrendipine, the beta 1-selective blocker metoprolol, mepindolol, the beta blocker with intrinsic activity and the angiotensin converting enzyme inhibitor enalapril were compared as monitored by 24-hour ambulatory blood pressure (BP) measurements. The study was designed so that a comparable decrease in casual BP values was obtained with all 4 drugs. If normotension was not achieved with monotherapy, a diuretic also was administered. Pretreatment casual BP and mean 24-hour ambulatory BP values did not differ between the 4 groups. Normotension as assessed by casual BP measurements was observed in all 4 groups after 6 months of therapy, there being no significant differences between the groups. However, significantly more diuretics were required in the mepindolol (n = 14) and in the enalapril (n = 20) groups compared to the nitrendipine (n = 5) and metoprolol (n = 7) groups. Despite comparable casual BP control, the 4 groups differed significantly in their mean 24-hour measurements. The greatest systolic and diastolic BP decreases were seen in the metoprolol group. Metoprolol was also the most effective drug in decreasing the frequency of systolic pressure peaks greater than 180 mm Hg. Both beta blockers and enalapril significantly decreased the morning BP increase compared to the values before treatment, while nitrendipine did not. These data show that casual BP measurement is not a good predictor of 24-hour BP in patients taking hypertensive therapy. Despite an equal degree of "office" BP control, different antihypertensive regimens do not confer the same degree of "nonoffice" BP control. PMID- 2220622 TI - Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. AB - Normal left ventricular systolic performance with impaired left ventricular diastolic filling may be present in a substantial number of patients with congestive heart failure (CHF). To evaluate the effect of oral verapamil in this subset, 20 men (mean age 68 +/- 5 years) with CHF, intact left ventricular function (ejection fraction greater than 45%) and abnormal diastolic filling (peak filling rate less than 2.5 end-diastolic volumes per second [edv/s]) were studied in a placebo-controlled, double-blind 5-week crossover trial. All patients underwent echocardiography to rule out significant valvular disease, and thallium-201 stress scintigraphy to exclude major active ischemia. Compared to baseline values, verapamil significantly improved exercise capacity by 33% (13.9 +/- 4.3 vs 10.7 +/- 3.4 minutes at baseline) and peak filling rate by 30% (2.29 +/- 0.54 vs 1.85 +/- 0.45 edv/s at baseline) (all p less than 0.05). Placebo values were 12.3 +/- 4.0 minutes and 2.16 +/- 0.48 edv/s, respectively (difference not significant for both). Improvement from baseline in an objective clinico-radiographic heart failure score (scale 0 to 13) was significantly greater with verapamil compared to placebo (median improvement in score: 3 vs 1, p less than 0.01). Mean ejection fraction and systolic blood pressure were unchanged from baseline; diastolic blood pressure and heart rate decreased to a small degree. Verapamil may have therapeutic efficacy in patients with CHF, preserved systolic function and impaired diastolic filling. PMID- 2220624 TI - Effects of preload reduction on mitral flow velocity pattern in normal subjects. AB - In the last few years, alterations in transmitral diastolic flow pattern have been used to assess changes in left ventricular diastolic properties. However, since diastolic flow primarily reflects the atrioventricular pressure gradient, loading conditions, as well as intrinsic left ventricular properties, should be able to affect this pattern. This study was selectively designed to decrease preload (a major determinant of the atrioventricular pressure gradient) in normal subjects to observe the effects on the Doppler transmitral flow pattern without pharmacologic interventions that may also affect left ventricular diastolic properties. In 12 normal subjects, preload was reduced by inflation of blood pressure cuffs placed at the level of the root of the 4 limbs. The peak velocity of early mitral flow (E wave) decreased from 62 +/- 8 to 51 +/- 7 cm/s (p less than 0.001), while no changes were found in the maximal velocity after atrial contraction; this caused a significant decrease in the ratio of these 2 velocities (the E to A ratio) from 1.5 +/- 0.3 to 1.1 +/- 0.1 (p less than 0.001). The time-velocity integral of early diastolic inflow decreased from 7.8 +/- 1.3 to 6.1 +/- 1.3 cm (p less than 0.001) with no significant changes of the time-velocity integral of inflow after atrial contraction. Therefore, preload reduction in normal subjects significantly reduces transmitral flow in early diastole with preserved late ventricular filling, producing a pattern that can mimic the changes previously described in left ventricular diastolic dysfunction. PMID- 2220623 TI - Changes in circulating norepinephrine with hemofiltration in advanced congestive heart failure. AB - In congestive heart failure (CHF), hemofiltration is associated with an obvious decrease in circulating norepinephrine. This method was used for investigating the mechanisms whereby plasma norepinephrine is increased in chronic CHF. In 23 cases of advanced CHF, hemofiltration (2,983 +/- 1,228 ml) lowered plasma norepinephrine by 515 +/- 444 pg/ml. This effect was prompt, persisted or became greater in the next 24 hours. It was not associated with significant changes in cardiac output, aortic pressure or systemic vascular resistance. It did not appear to depend on variations in parameters related to the sympathetic activity, such as plasma renin, right atrial, wedge pulmonary artery and renal perfusion pressures, and was independent of duration and amount of hemofiltration. These observations did not support the concept that the norepinephrine decrease was the main consequence of a neural sympathetic inhibition. Hemofiltration increased diuresis by 606 +/- 415 ml; changes were prompt and correlated inversely (r = 0.7; p less than 0.01) with those in plasma norepinephrine. The same unknown mechanism of the increased urinary output might potentiate the norepinephrine removal from the blood by the kidney, or hemofiltration and the augmented diuresis might result in a regression of congestion of lungs and kidneys, leading to an improved extraction of norepinephrine. In CHF, a relation may exist between fluid retention and norepinephrine and in advanced stages, circulating norepinephrine, although strikingly increased, is devoid of important cardiovascular effects. At these stages, plasma norepinephrine is probably unreliable as an index of the sympathetic neural activity. PMID- 2220625 TI - Clinical experience with technetium-99m teboroxime, a neutral, lipophilic myocardial perfusion imaging agent. AB - Technetium-99m (Tc-99m) teboroxime is a new technetium-based myocardial perfusion imaging agent (investigational code = SQ30217 [Cardiotec, Squibb Diagnostics]). A member of a class of neutral, lipophilic, technetium-containing complexes known as boronic acid adducts of technetium dioxime (BATO) complexes, this agent is chemically very different from the cationic tracer thallium-201 (Tl-201) and from the cationic technetium complex Tc-99m sestamibi (Cardiolite, Du Pont Imaging Agents). Tc-99m teboroxime has high myocardial extraction, rapid blood clearance, little lung uptake and rapid myocardial washout. A biexponential pattern of myocardial washout is demonstrated in animals and in man. Effective half-lives of the 2 washout components in man are 5.2 minutes and 3.8 hours and represent approximately 66 and 33% of the myocardial activity, respectively. The first half life for the myocardium is approximately 11 minutes. As the agent washes out of the heart, hepatic uptake occurs, peaking at about 5 minutes after injection. The liver is the major organ of excretion and receives, along with the large bowel, the largest radiation dose. Rapid imaging protocols using standard cameras have achieved good myocardial counts from 3 planar views acquired over a 4- to 5 minute period or for single photon emission computed tomography (SPECT) images acquired over a 10-minute period. An entire stress/rest procedure can be completed in 1 hour. Analysis of data from 155 patients from 4 centers using planar or SPECT imaging showed a sensitivity and specificity for blinded readings of 82 and 91%, respectively, when compared against overall clinical impression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220626 TI - Percutaneous excimer laser coronary angioplasty. AB - To determine the efficacy of percutaneous excimer laser coronary angioplasty as an adjunct or alternative to conventional balloon angioplasty, 55 patients were studied in a multicenter trial. These patients underwent the procedure using a modification of conventional balloon angioplasty technique. A first-generation, 1.6-mm diameter catheter constructed of 12 individual silica fibers concentrically arranged around a guidewire lumen was used. Catheter tip energy density varied from 35 to 50 mJ/mm2. The mean number of pulses delivered at 20 Hz was 1,272 +/- 1,345. Acute success was defined as a greater than or equal to 20% increase in stenotic diameter and a lumen of greater than or equal to 1 mm in diameter after laser treatment. Acute success was achieved in 46 of 55 (84%) patients. Adjunctive balloon angioplasty was performed on 41 patients (75%). The percent diameter stenosis as determined by quantitative angiography decreased from a baseline of 83 +/- 14 to 49 +/- 11% after laser treatment and to 38 +/- 12% in patients undergoing adjunctive balloon angioplasty. The mean minimal stenotic diameter increased from a baseline of 0.5 +/- 0.4 to 1.6 +/- 0.5 mm after laser treatment and to 2.1 +/- 0.5 mm after balloon angioplasty. There were no deaths and no vascular perforations. One patient (1.8%) required emergency coronary bypass surgery. These data suggest that excimer laser energy delivered percutaneously by specially constructed catheters can safely ablate atheroma and reduce coronary stenoses. PMID- 2220627 TI - Results of percutaneous transluminal coronary angioplasty in patients greater than or equal to 65 years of age (from the 1985 to 1986 National Heart, Lung, and Blood Institute's Coronary Angioplasty Registry). AB - The 1985 to 1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry series of 1,801 initial procedures included 486 patients age greater than or equal to 65 years (elderly). In comparison to younger patients, a greater proportion of elderly patients were women and had unstable angina. Elderly patients had more history of hypertension and more history of congestive heart failure. Although the elderly had more extensive vessel disease, the numbers of lesions and vessels attempted with PTCA were similar in the older and younger cohorts. Angiographic success rates were similar for all age groups. Although complication rates in the catheterization laboratory did not differ, patients greater than or equal to 65 years were much more likely to require emergency coronary artery bypass graft surgery (CABG) (5.4 vs 2.8%, p less than 0.05) or elective CABG (3.9 vs 1.6%, p less than 0.01). The in-hospital death rate was considerably higher among the elderly (3.1 vs 0.2%, p less than 0.01). At 2-year follow-up, symptomatic status and cumulative rates of myocardial infarction, CABG and repeat PTCA were similar for elderly and younger patients. The death rate after 2 years was higher among elderly patients (8.8% of patients greater than or equal to 65 years vs 2.9% of patients less than 65 years, p less than 0.01). When the relative risk of death for the elderly was adjusted for factors more prevalent among those greater than or equal to 65 years (history of congestive heart failure, multivessel disease, unstable angina, history of hypertension and female gender), the relative risk remained significant but was substantially reduced (from 3.3 to 2.4). PMID- 2220628 TI - Quantitative angiographic assessment of elastic recoil after percutaneous transluminal coronary angioplasty. AB - Little is known about the elastic behavior of the coronary vessel wall directly after percutaneous transluminal coronary angioplasty (PTCA). Minimal luminal cross-sectional areas of 151 successfully dilated lesions were studied in 136 patients during balloon inflation and directly after withdrawal of the balloon. The circumvent geometric assumptions about the shape of the stenosis after PTCA, a videodensitometric analysis technique was used for the assessment of vascular cross-sectional areas. Elastic recoil was defined as the difference between balloon cross-sectional area of the largest balloon used at the highest pressure and minimal luminal cross-sectional area after PTCA. Mean balloon cross-sectional area was 5.2 +/- 1.6 mm2 with a mean minimal cross-sectional area of 2.8 +/- 1.4 mm2 immediately after inflation. Oversizing of the balloon (balloon artery ratio greater than 1) led to more recoil (0.8 +/- 0.3 vs 0.6 +/- 0.3 mm, p less than 0.001), suggestive of an elastic phenomenon. A difference in recoil of the 3 main coronary branches was observed: left anterior descending artery 2.7 +/- 1.3 mm2, circumflex artery 2.3 +/- 1.2 mm2 and right coronary artery 1.9 +/- 1.5 mm2 (p less than 0.025). The difference was still statistically significant if adjusted for reference area. Thus, nearly 50% of the theoretically achievable cross sectional area (i.e., balloon cross-sectional area) is lost shortly after balloon deflation. PMID- 2220629 TI - Timing and mechanism of in-hospital and late death after primary coronary angioplasty during acute myocardial infarction. AB - The effect of early myocardial reperfusion on patterns of death after acute myocardial infarction (AMI) is unknown. Thus, the mechanism and timing of in hospital and late deaths among a group of 614 patients treated with coronary angioplasty without antecedent thrombolytic therapy for AMI were determined. Death occurred in 49 patients (8%) before hospital discharge. Four patients died in the catheterization laboratory. Death was due to cardiogenic shock in 22 patients, acute vessel reclosure in 5 patients, was sudden in 8 patients and followed elective coronary artery bypass surgery in 8 patients. Cardiac rupture was observed in only 2 patients after failed infarct angioplasty, and did not occur among the 574 patients with successful infarct reperfusion. Intracranial hemorrhage did not occur. Multivariate predictors of in-hospital death included failed infarct angioplasty, cardiogenic shock, 3-vessel coronary artery disease and age greater than or equal to 70 years. During a follow-up period of 32 +/- 21 months (range 1 to 87), 55 patients died. The cause of death was cardiac in 36 patients, including an arrhythmic death in 23 patients and was due to circulatory failure in 13 others. One patient died of reinfarction due to late reclosure of the infarct artery. Actuarial survival curves demonstrated overall survival after hospital discharge of 95 and 87% at 1 and 4 years, respectively. Freedom from cardiac death at 1 and 4 years was 96 and 92%. Multivariate predictors of late death included 3-vessel disease, a baseline ejection fraction of less than or equal to 40%, age greater than 70 years and female gender.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220630 TI - Circadian rhythm of heart rate variability after acute myocardial infarction and its influence on the prognostic value of heart rate variability. AB - This study examined heart rate (HR) variability in patients surviving acute myocardial infarction (AMI) to find the optimum time and duration of recording of the ambulatory electrocardiogram for the prediction of the risk of sudden cardiac death, or serious arrhythmic events, or both. Twenty patients (group I) who initially survived an AMI but later experienced serious events (death or symptomatic sustained ventricular tachycardia) during a 6-month follow-up were compared with 20 patients (group II) who remained free of complications for greater than 6 months after discharge. Groups I and II were matched with regard to age, gender, infarct site, ejection fraction, and beta-blocker treatment. HR variability was assessed in the 24-hour electrocardiograms recorded during the first 2 weeks after an AMI and in various portions of the complete 24-hour recording, with both the beginning and the length of the analyzed portion varied by 20 minutes (a total of 5,113 possibilities). The maximum reduction of HR variability in group I patients was systematically found when assessing HR variability in recordings starting approximately at 6 A.M. and lasting for approximately 8 hours. In the low-risk patient, the diurnal rhythm of HR variability is more marked than in the high-risk patient and the long-term components of HR variability due to the diurnal variation must be included in the measurement of HR variability when using it as a long-term predictor of risk from arrhythmic events after an AMI. PMID- 2220631 TI - Doppler assessment of left ventricular filling pattern in silent ischemia in patients with Prinzmetal's angina. AB - Spontaneous angina is an ideal condition in which to study left ventricular (LV) dysfunction induced by acute myocardial ischemia. In 6 patients with Prinzmetal's angina, LV diastolic function during 16 episodes of spontaneous angina was studied by simultaneous recordings of electrocardiographic (ECG), echocardiographic and hemodynamic parameters. In particular, pulsed Doppler echocardiography measured peak velocity of early (E) and late (A) transmitral flow and E/A ratio, as indexes of relative early versus late LV filling. During the ischemic attacks, the time sequence of pulsed Doppler echocardiographic and ECG changes showed 3 distinct phases: (1) "waxing phase: transmitral flow changes with minimal ECG modifications (E/A = 0.85 +/- 0.1); (2) "steady" phase: maximal ECG changes (E/A = 0.9 +/- 0.1); and (3) "waning" phase: regression of the ECG changes (E/A = 1.26 +/- 0.15). In each phase, E/A ratio showed a significant difference from the baseline value (E/A = 1.17 +/- 0.2) as a result of changes in E, suggesting that myocardial ischemia affects mainly the early phase of diastole. In the waxing phase, LV diastolic dysfunction preceded systolic abnormalities, as documented by a significant reduction of E/A ratio in the absence of alterations in LV ejection fraction, as well as in systemic arterial and pulmonary wedge pressures. Finally, all the recorded parameters were consistent with LV "contractile rebound" occurring in the waning phase and affecting both diastole and systole. PMID- 2220633 TI - Comparison of direct and indirect measures of systemic arterial pressure during weightlifting in coronary artery disease. AB - Based on auscultation measurements after exercise, circuit weight training in cardiac patients has been reported to provoke minimal increases in systolic pressure. Direct (brachial artery catheter) and indirect (sphygmomanometry) measures of blood pressure were compared at rest, during lifting with the legs (approximately the fourth, ninth and fourteenth repetition) and during 2 minutes of recovery after lifting with the arms and legs. Subjects performed 15 repetitions of single-arm curl, single-arm military press and single- and double leg press exercises at 40 and 60% of the maximum load that could be lifted once on a multistation weightlifting apparatus. Indirect measures of systolic pressure at rest were 13% less than those recorded directly (130 +/- 7 vs 149 +/- 8 torr; p less than 0.01); diastolic pressures were similar using either method. This pattern was maintained during lifting with the legs at both intensities, and after exercise with both the legs and the arms. The mean systolic pressure recorded indirectly immediately after exercise was 63 torr (31%) and 76 torr (34%) less than the average peak intraarterial value recorded during leg and arm exercises, respectively. The highest intraarterial pressures were generated during the final repetitions of the set; immediately after the last repetition, both systolic and diastolic pressures rapidly decreased. It is concluded that indirect estimates of systolic pressure are significantly less than true arterial values at rest, and during and after lifting. Moreover, indirect measurements after lifting do not allow accurate conclusions to be drawn about the arterial pressures generated during lifting because of the rapid decrease in pressure that occurs after exercise. PMID- 2220632 TI - Aortic calcified plaques and cardiovascular disease (the Framingham Study). AB - The relation between the presence of calcified plaques in the thoracic aorta, as detected on chest x-rays, and the development of cardiovascular disease is examined during 12 years of follow-up of the Framingham cohort (n = 5,209). The prevalence of aortic calcified plaques approximately doubled with each decade of age, with only a trivial male predominance. Its presence was associated with a twofold increase in risk of cardiovascular death in men and women younger than age 65, even after other risk factors were taken into account. Similar increases in risk were found for coronary artery disease, stroke and intermittent claudication among middle-aged women. In middle-aged men these risks were less marked. The predictive value of aortic calcified plaques generally diminished with age. Risk of sudden coronary death in men with calcified plaques in the thoracic aorta ranged from a sevenfold increase at age 35 to no excess risk at age 70 years. These results support the view that atherosclerosis is a generalized process. The finding of aortic calcified plaques in a relatively young subject on a routine chest x-ray should be regarded as a sign for potential development of clinically manifest atherosclerotic disease in the cardiac, cerebral and peripheral arterial circulation. PMID- 2220634 TI - Response of angiographically normal and atherosclerotic left anterior descending coronary arteries to acetylcholine. AB - Acetylcholine-induced constriction of human coronary arteries in vivo is commonly attributed to endothelial dysfunction. To examine the effects of 2 other important determinants of vascular responses--namely, agonist concentration and the segment of circulation under study--the diameters of proximal, middle and distal segments of the left anterior descending artery (LAD) and coronary sinus oxygen saturation were measured in 10 patients with angiographically normal coronary arteries (group 1) and in 7 patients with coronary atherosclerosis (group 2) after intracoronary acetylcholine was infused at concentrations from 10(-7)M to between 10(-4)M and 10(-2)M. In group 1, acetylcholine caused minor (less than or equal to 6%) but progressive dilatation of the LAD up to 10(-4)M, but constriction, particularly of the distal segments and tertiary branches, occurred at higher concentrations. Over the same concentration range, coronary sinus oxygen saturation rose progressively from a basal level of 36 +/- 3% to a maximum of 72 +/- 3% in the absence of changes in heart rate and blood pressure, suggesting marked progressive dilatation of resistance vessels. Concentrations greater than or equal to 10(-3)M caused intense constriction of distal epicardial vessels and, in some cases, anginal pain and objective signs of ischemia. Conversely, in group 2, acetylcholine (infused only up to 10(-4)M for ethical reasons) failed to cause significant changes in LAD diameter. These data suggest that the local acetylcholine concentration and coronary vascular segment under study may determine the observed response to at least an equivalent extent as does the presence or absence of coronary atherosclerosis, raising the question of whether a constrictor response to intracoronary acetylcholine reliably indicates the presence of coronary atherosclerosis. PMID- 2220635 TI - Clinical and electrophysiologic characteristics of patients with antidromic circus movement tachycardia in the Wolff-Parkinson-White syndrome. AB - Antidromic circus movement tachycardia was documented in 36 of 345 consecutive patients with Wolff-Parkinson-White syndrome undergoing detailed electrophysiologic evaluation. Twenty-six patients were men and 10 were women (mean age +/- standard deviation 26 +/- 12 years [range 12 to 45]). Multiple accessory pathways were identified in 12 of these 36 patients (33%). Ten of the patients (67%) with clinically documented antidromic tachycardia had multiple accessory pathways. Dizziness and syncope occurred in 61 and 50% of patients with antidromic circus movement tachycardia. Six patients had clinical documentation of atrial fibrillation, and 4 patients (11%) were resuscitated from ventricular fibrillation. In the 36 patients, 56 distinct antidromic tachycardias were recorded and several different pathways were observed. Orthodromic tachycardia was the most frequently associated arrhythmia (72%). Dual atrioventricular nodal pathways were present in 12 patients (33%); however, atrioventricular nodal tachycardia could be initiated in only 2 of them. Interruption of the accessory pathway was successfully performed in all 20 patients undergoing surgery. PMID- 2220636 TI - Persistence of arrhythmia exercise response in healthy young men. AB - This study assesses the persistence of arrhythmia at rest or during exercise tests, or both, after a mean follow-up period of 6.7 years in 76 young men (mean age 21.5 years) without evidence of organic heart disease. The exercise test was performed using a near-maximal protocol based on progressively increasing intermittent work loads, each of 5 minutes' duration. The initial work load was 50 W. The electrocardiogram was continuously registered throughout all stages of the examination. Arrhythmia was defined as the occurrence of greater than or equal to 1 supraventricular or 1 ventricular premature beat at any stage of the examination. At the follow-up examination, the rate of persistence of arrhythmia did not differ significantly among the subgroups, irrespective of follow-up interval, type of arrhythmia, or arrhythmia patterns of response to exercise. Two dimensional echocardiography did not show any structural abnormalities and Doppler examination did not demonstrate significant abnormal flow patterns. Our data show that almost all patients continued to present arrhythmia after the follow-up period, without any evidence of development of organic heart disease. Moreover, the arrhythmia pattern of response to exercise remained constant throughout the years. At this time, arrhythmia without underlying heart disease seems to be of a benign natural course in these young men. PMID- 2220637 TI - Electrocardiographic signal-averaging during atrial pacing and effect of cycle length on the terminal QRS in patients with and without inducible ventricular tachycardia. AB - Electrocardiographic signal-averaging during sinus rhythm (61 to 99 beats/min) and atrial pacing (100 to 171 beats/min) were performed to determine the effect of heart rate on late potentials in 15 patients without (group 1) and 7 patients with (group 2) inducible sustained ventricular tachycardia (VT). In sinus rhythm (79 +/- 12 vs 77 +/- 12 beats/min, difference not significant), the duration of the low-amplitude signal less than 40 microV was longer in group 2 than group 1 (43 +/- 21 vs 26 +/- 8 ms, p = 0.034) and more patients had late potentials (57 vs 7%, p = 0.021), but QRS duration (121 +/- 32 vs 98 +/- 19 ms) and terminal voltage (33 +/- 33 vs 50 +/- 26 ms) were not significantly different. With atrial pacing in group 1 (128 +/- 16 beats/min), 3 patients developed a simultaneous decrease in terminal voltage and an increase in terminal QRS duration consistent with a late potential, but mean total and terminal durations were unchanged. Terminal voltage increased (50 +/- 26 to 59 +/- 40) but not significantly. With atrial pacing in group 2 (119 +/- 12 beats/min) all patients either had a late potential or developed a simultaneous decrease in terminal voltage and an increase in terminal QRS duration (p = 0.001 vs group 1). Root mean square (p = 0.001 vs group 1). Root mean square voltage decreased (33 +/- 23 to 22 +/- 23) and became significantly different from group 1 (p = 0.017). Mean QRS duration, root mean square terminal voltage and low-amplitude terminal QRS duration, however, were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220638 TI - Comparison of intravenous amrinone and dobutamine in congestive heart failure due to idiopathic dilated cardiomyopathy. AB - A prospective randomized study was performed in 46 consecutive patients with refractory congestive heart failure (CHF) due to idiopathic dilated cardiomyopathy to compare the hemodynamic responses to 48-hour infusions of amrinone and dobutamine. Both drugs substantially reduced pulmonary arterial wedge pressure, right atrial pressure and systemic vascular resistance and increased cardiac index. Amrinone caused a greater decrease in right atrial pressure than dobutamine (p less than 0.02) and had a positive chronotropic effect not observed with dobutamine (p less than 0.01). The increase in heart rate produced by amrinone correlated inversely with the changes in right atrial and pulmonary arterial wedge pressures, suggesting a baroreceptor response to reduced preload. Dobutamine produced a larger increase in stroke volume index than amrinone (p less than 0.01). Ninety-one percent of patients receiving amrinone and only 65% receiving dobutamine had reduction of greater than or equal to 30% in pulmonary arterial wedge pressure (p less than 0.05). Cardiac index increased greater than or equal to 30% in similar numbers of patients given amrinone (74%) and dobutamine (65%). Negative fluid balance was recorded in all patients receiving amrinone and in 78% of patients receiving dobutamine (p less than 0.05). Target hemodynamic criteria were achieved in 83% of patients receiving 10 micrograms/kg/min of amrinone. The effective maintenance dose of dobutamine was extremely variable. No clinically important adverse effects were observed with either drug regimen. Both amrinone and dobutamine are effective and safe agents for short-term parenteral therapy of patients with dilated cardiomyopathy in severe CHF that is unresponsive to oral medication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220639 TI - Comparison of frequency of late potentials in idiopathic dilated cardiomyopathy and ischemic cardiomyopathy with advanced congestive heart failure and their usefulness in predicting sudden death. AB - Signal-averaged electrocardiograms were obtained in 62 consecutive patients with advanced congestive heart failure (CHF) undergoing evaluation for possible heart transplantation to determine if late potentials: (1) provide unique information compared to assessment of ventricular ectopic activity on ambulatory electrocardiogram, and (2) identify a subgroup of CHF patients with higher sudden death risk. Patients with a history of cardiac arrest or sustained ventricular tachycardia were excluded. CHF was due to old myocardial infarction in 40 patients and idiopathic dilated cardiomyopathy in 22 patients. Late potentials were present in 16 of 40 (40%) patients with old infarction but in only 3 of 22 (14%) patients with nonischemic CHF (p = 0.03). Twenty-four-hour ambulatory electrocardiograms were obtained in 34 patients (55%). Total ventricular ectopic activity and repetitive forms of ectopy were similar in patients with and without late potentials. Nine patients died suddenly, 9 had nonsudden death, 15 underwent heart transplantation and 29 were alive and well after a mean follow-up of 218 +/ 154 days. At 1 year, the actuarial risk of death was 37% and of sudden death was 20%. Sudden death risk was 12% in patients with late potentials versus 21% in those without (p = 0.73). Thus, the incidence of the arrhythmia substrate producing late potentials depends on the CHF etiology. The signal-averaged electrocardiogram and ambulatory electrocardiogram provide independent information for possible risk assessment in CHF. However, late potentials are poor predictors of sudden death risk when CHF is advanced, possibly due to the heterogeneity of causes of sudden death--ventricular tachycardia being only 1 of many possible mechanisms. PMID- 2220640 TI - Improvement in early diastolic filling dynamics after aortic valve replacement. AB - With use of ultrafast computed tomography, 13 patients undergoing aortic valve replacement for aortic stenosis were prospectively followed to evaluate the relation between left ventricular mass and diastolic function. Studies were done before intervention, and then at 4 and 8 months later. Mass decreased from 161 +/ 11 g/m2 (+/- standard error of the mean) at baseline to 106 +/- 5 g/m2, and then to 97 +/- 7 g/m2 at 4 and 8 months, respectively, in 12 patients who demonstrated significant (greater than 20%) mass regression after operation. One patient failed to show significant changes in mass. Diastolic function, as defined by the peak filling rate of early diastole, improved (p less than 0.02) in the group with mass regression, from 2.11 +/- 0.17 s-1 at baseline to 2.12 +/- 0.23 s-1, and then to 2.62 +/- 0.26 s-1 at 4 and 8 months, respectively. Improvement in the time to peak filling rate was also noted. Heart rates were unchanged, whereas end diastolic volumes decreased and ejection fractions increased slightly. Postoperative increase in peak filling rate correlated with regression of ventricular mass to within normal range (+/- 2 standard deviations) and attainment of New York Heart Association class I status by 8 months (p less than 0.02). Thus, improvement in diastolic function can be seen after aortic valve surgery and is associated with improved functional class. Diastolic function improves later than the regression in wall mass and may imply a delayed remodeling of the ventricle. PMID- 2220641 TI - Lipoprotein and hepatic lipase activity and high-density lipoprotein subclasses after cardiac transplantation. AB - Atherosclerosis is the leading obstacle to long-term survival in cardiac transplant patients. Increases in plasma triglycerides and lipoprotein cholesterol levels occur after transplantation that may contribute to transplant atherosclerosis. The etiology of this increase is unclear. We investigated the interaction of immunosuppressive medications with plasma triglycerides, low density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, the HDL subclasses HDL2 and HDL3 cholesterol, and hepatic and lipoprotein lipase activity in 72 consecutive cardiac transplant patients compared to 51 healthy control subjects. In the transplantation group, greater concentrations of plasma triglyceride (80%, p less than 0.001), LDL cholesterol (16%, p less than 0.005) and hepatic lipase activity (100%, p less than 0.001) were noted, whereas lipoprotein lipase activity was noted to be significantly lower (124%, p less than 0.001). No difference was detected in HDL, HDL2, or HDL3 cholesterol. Cyclosporine dose was significantly associated with hepatic lipase activity (r = 0.33, p less than 0.02) and inversely associated with lipoprotein lipase activity (r = -0.28, p less than 0.05). Lipoprotein lipase activity after transplantation correlated inversely with triglycerides (r = -0.36, p less than 0.002) and positively with HDL cholesterol (r = 0.23, p less than 0.05) and HDL2 cholesterol (r = 0.29, p less than 0.05). Hepatic lipase activity correlated inversely with LDL cholesterol (r = -0.21, p less than 0.08). In multiple regression analysis, cyclosporine dose was the major source of variation in hepatic lipase activity. PMID- 2220642 TI - Serial evaluation of lipid profiles and risk factors for development of hyperlipidemia after cardiac transplantation. AB - To determine the prevalence, time course and factors responsible for hyperlipidemia after heart transplantation, 83 consecutive 1-year survivors were studied. By 1 year, 83% of patients had serum total cholesterol levels greater than 5.2 mmol/liter (200 mg/dl) and 28% of the patients had serum total cholesterol higher than the age- and sex-matched ninety-fifth percentile. At the end of 1-year follow-up, serum total cholesterol correlated with the recipient age (p less than 0.0001), the preoperative cholesterol level (p less than 0.001), the actual dose of maintenance prednisone at 1 year (p less than 0.02) and the cumulative 1-year steroid dose (p less than 0.03). Similarly, the serum triglyceride level at 1 year correlated with the pretransplant level of serum triglycerides (p less than 0.0001), recipient age (p less than 0.03) and cumulative 1-year steroid dose (p less than 0.03). Patients with a pretransplant diagnosis of coronary artery disease had a significantly higher level of serum total cholesterol and triglyceride levels at 1 year (p less than 0.02 and p less than 0.03, respectively). Heart transplant recipients with body mass index greater than or equal to 25 kg/m2 also presented with significantly elevated serum total cholesterol and triglyceride levels at 1 year compared with nonobese patients (p less than 0.01 and p less than 0.002, respectively). Hyperlipidemia occurs frequently and is detected within the first month after heart transplantation. Optimal management of this problem requires further study. PMID- 2220643 TI - Electrocardiographic Q-wave inconstancy in inferior wall myocardial infarction. PMID- 2220644 TI - ST elevation in the right chest leads in anterior wall left ventricular acute myocardial infarction. PMID- 2220645 TI - Emergency stenting for refractory acute coronary artery occlusion during coronary angioplasty. PMID- 2220646 TI - Efficacy of acebutolol after acute myocardial infarction (the APSI trial). The APSI Investigators. AB - A randomized, placebo-controlled trial was carried out to determine the effectiveness of acebutolol in preventing late death in high-risk patients surviving an acute myocardial infarction (MI). The average 1-year mortality rate in placebo groups of 9 trials of beta blockers in post-MI patients was 7.2% compared with 17% in a nonselected cohort of patients who had survived at least 7 days after an MI. The mandate for this trial was based on the fact that high-risk patients whose mortality rate exceeds 20% have not been enrolled in significant numbers in previous trials. It remains to be proved whether beta-blocking therapy in this patient population is beneficial. Selection of high-risk patients for inclusion in the trial was based on an algorithm set up from the Essai de Prevention Secondaire de l'Infarctus du Myocarde Registry. At the time of the second interim analysis, the mortality rate in the placebo group was 12%, lower than expected (greater than or equal to 20%). The trial was stopped; at that time, 309 patients had been allocated to placebo and 298 patients to acebutolol therapy. After 318 days, there were 17 deaths in the acebutolol-treated group and 34 in the placebo group, a reduction in total mortality of 48% (p = 0.019). There were 30 vascular deaths in the placebo group and 12 in the acebutolol group. Thus, cardiovascular mortality with acebutolol was reduced by 58% (p = 0.006). The incidence of all cardiovascular-related deaths was lower in the acebutolol treated group. The total reduction in mortality did not appear to be correlated with secondary risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220647 TI - Characteristics of participants at baseline in the Treatment of Mild Hypertension Study (TOMHS). AB - The Treatment of Mild Hypertension Study (TOMHS) is a randomized, double-blind clinical trial currently being conducted to compare the effects of nonpharmacologic therapy alone with those of 1 of 5 active drug regimens combined with nonpharmacologic therapy, for long-term management of patients with mild hypertension. Six classes of drugs were studied: (1) acebutolol (beta blocker), (2) amlodipine (calcium antagonist), (3) chlorthalidone (diuretic), (4) doxazosin (alpha 1 antagonist), (5) enalapril (angiotensin-converting enzyme inhibitor) and (6) placebo. All participants received nutritional-hygienic advice to reduce weight and sodium and alcohol intakes and to increase physical activity. End points include blood pressure change, side effects and quality-of-life indices; incidence of electrocardiographic and echocardiographic abnormalities; and incidence of cardiovascular clinical events, including death, among participants receiving drugs as first-step treatment as well as nonpharmacologic treatment compared with incidence among those participants randomized to nonpharmacologic treatment only as the initial step. PMID- 2220648 TI - Arterial protection: a neglected but crucial therapeutic goal. AB - Hypertension is accompanied by 2 major types of arterial pathologic conditions: smooth muscle hypertrophy of arteriolar resistance vessels and atherosclerosis, primarily involving the larger arteries. Smooth muscle hypertrophy may develop either as a secondary defense against elevated intravascular pressure or as a primary defect responsible for the increased pressure. Insulin and a number of other trophic stimuli may play a pathogenetic role in vascular hypertrophy. Reducing blood pressure and trophic stimuli may cause hypertrophy to be reversed. Because atherosclerosis may be markedly accelerated by hypertension, especially in the presence of concomitant risk factors, such as hypercholesterolemia, cigarette smoking and diabetes mellitus, antihypertensive treatment may attenuate or even reverse the extent of atherosclerosis, but only when the causative factors are also corrected. Some commonly used antihypertensive agents, e.g., diuretics and beta blockers without intrinsic sympathomimetic activity, often aggravate hypercholesterolemia and glucose intolerance, thereby diminishing their potential protective value. Other types of drug therapy, such as alpha blockers, beta blockers with intrinsic sympathomimetic activity or other vasodilator activity, angiotensin-converting enzyme inhibitors and calcium entry blockers that may not induce biochemical changes, should provide better control of multiple risks and thereby better protection against atherosclerosis. With a better understanding of how hypertension induces arterial damage, clinicians will be able to provide more appropriate treatment and, it is hoped, alleviate such damage. PMID- 2220649 TI - Mechanical factors in large artery disease and antihypertensive drugs. AB - Hypertension may induce early alterations in large arteries by 2 mechanical stresses: one related to intravascular pressure, the other to blood flow dynamics. Distending pressure force acts in a circumferential direction, inducing decreased arterial distensibility. Arterial distensibility can be evaluated in humans by measurement of arterial compliance and pulse-wave velocity. It is well established that in chronic hypertension age and elevated pressure act together to increase arterial rigidity. Blood flow dynamics induce frictional forces in the endothelial surfaces of arteries. These forces, expressed by shear stress, are proportional to the viscosity of the blood and to the velocity gradient at the arterial wall. Measurement of blood viscosity and evaluation of velocity profile in the brachial arteries of hypertensive subjects have shown a reduction in wall shear rate and stress despite the elevation in blood viscosity. Several studies have shown that drug therapy that successfully reduces blood pressure does not necessarily improve arterial compliance. In contrast, few data are available on the effects of antihypertensive medication on arterial wall shear in humans. Arterial compliance and wall shear stress are 2 main therapeutic targets of potential importance in the physiopharmacologic approach to the effects of hypertension on atherogenesis. PMID- 2220650 TI - Documentation of the effective length of action of antihypertensive treatment. AB - The technique of automated ambulatory blood pressure (BP) monitoring offers an innovative means for measuring BP throughout the 24-hour period. Recently available compact monitoring instruments have been shown to be accurate and to provide reproducible measurements of the circadian BP pattern. The monitoring procedure is advantageous in that it minimizes or avoids placebo effects during therapeutic trials. Moreover, its power makes it possible to draw statistically valid conclusions regarding efficacy in fewer patients than would be required if conventional methods were used. This procedure also enhances the diagnosis of hypertension by identifying patients with "office" or "white coat" hypertension, and thereby facilitates assessment of treatment effects in those patients who are truly hypertensive. Automated monitoring measures BP at critical times of the day, including the preawakening and early morning hours, and it enables peak and trough antihypertensive drug effects to be carefully quantified. Since patient compliance appears to be enhanced with once- or twice-daily dosing, antihypertensive agents with long durations of action (24 hours) are of considerable interest. This report reviews some recent studies in which the monitoring technique has been used to measure the efficacy and duration of action of differing antihypertensive drugs. PMID- 2220651 TI - Acebutolol effects on lipid profile. AB - The relation between lipid profile and the incidence of coronary artery disease has been confirmed by the results of epidemiologic and intervention studies. Among antihypertensive agents, beta blockers, particularly those without intrinsic sympathomimetic activity (ISA), are generally reported to have negative effects on lipids, which may increase the risk of coronary artery disease. The ongoing Treatment of Mild Hypertension Study, now in its third year, has evaluated 847 patients to date with regard to lipid profile. Additional end points measured in this multicenter, randomized, controlled, double-blind study include blood pressure reduction and target organ deterioration. During the trial, all patients received nutritional and behavioral counselling to modify their diet, exercise habits and alcohol and sodium consumption to control their hypertension by nonpharmacologic means. In addition, some patients were randomized to receive low doses of 1 of the 5 classes of antihypertensive medication: acebutolol, a beta blocker with ISA (n = 124); amlodipine, a calcium channel blocker (n = 122); chlorthalidone, a diuretic (n = 125); doxazosin, an alpha blocker (n = 128); enalapril, an angiotensin-converting enzyme inhibitor (n = 127) or placebo (n = 221). At 1 year, acebutolol showed a statistically significant (p less than 0.001) decrease in total cholesterol (-12.7 mg/dl) compared with placebo (-5.2 mg/dl) and with chlorthalidone (1.0 mg/dl); a significant (p less than 0.001) decrease in low-density lipoprotein cholesterol ( 6.0 mg/dl) compared with placebo (+0.7 mg/dl) and with chlorthalidone (+8.0 mg/dl) and no change in high-density lipoprotein cholesterol (-0.4 mg/dl). PMID- 2220652 TI - Dissociation and displacement: where goes the "ouch?". AB - Hypnosis is widely used to relieve pain. Current theory emphasizes its dissociative features. Multiple personality patients can eliminate pain in the primary personality by displacing it into underlying alters. The Hilgards demonstrated that normal hypnotized subjects can similarly dissociate pain into a covert cognitive structural system which they called the "hidden observer." The Watkins discovered that "hidden observers" appeared to be the same phenomenon as "ego states." "Ego-state theory" assumes that human personality develops through integration and differentiation. At one end of the continuum, "differentiation" is adaptive. Ego states possess relatively permeable boundaries as in normal moods. At the other end ego-state boundaries become less permeable. Normal "differentiation" becomes maladaptive "dissociation" and multiple personalities may be created. In the intermediate range of the differentiation/dissociation continuum, "covert" ego states can be found in many normal subjects who volunteer for hypnotic laboratory experiments. Normal individuals, like multiple personalities and "hidden observer" subjects, can displace (dissociate) pain into "covert" ego states. The pain is not eliminated. This suggests that when we remove pain by hypnosis we may not be getting away "scot-free." PMID- 2220653 TI - Etiology and treatment of dental anxiety and phobia. AB - Dental anxiety and phobia afflict millions of people. Dental patients who are anxious anticipate pain and feel vulnerable and out of control. Hypnotherapy to alleviate dental anxiety and phobias has received clinical and empirical support. Our purpose in this paper is to provide a body of objective data from American Society of Clinical Hypnosis members regarding incidence rates and the relative importance of various etiological and conceptual issues in the development and maintenance of dental anxiety and treatment interventions. From these data, we constructed a model of etiology, maintenance, and treatment of dental anxiety. PMID- 2220654 TI - Characteristics of change in Ericksonian hypnotherapy: a cognitive-psychological perspective. AB - Milton H. Erickson's approach to hypnosis and psychotherapy has established itself as a therapeutic paradigm in recent years. As its popularity grows, however, myths and misconceptions about his approach have also emerged. Some of them claim falsely that Erickson's therapy consists of nothing more than a set of quick, symptom-management formulae. To understand Erickson's hypnotic psychotherapy in a proper context, a systematic review is warranted. In this article I have examined, from a cognitive-psychological perspective, four of the major characteristics of therapeutic change underlying Erickson's work: (a) self efficacy, (b) spontaneous compliance, (c) cognitive/experiential reorganization, and (d) global distribution of information. Drawing on Erickson's original writing, this paper integrates his published cases into an existing theoretical and empirical framework. Clinical implications are also discussed. PMID- 2220655 TI - Hypnotic susceptibility and experimental pain reduction. AB - We exposed 24 subjects high in hypnotic susceptibility and 24 subjects low in hypnotic susceptibility to a cold-pressor pain stimulus under either hypnotic or waking conditions, using each of two pain-reduction strategies (analgesia and distraction) separately. Trance depth level was held constant for hypnotized subjects. We used pain-tolerance levels as measures of pain, and we analyzed them by survival analysis. High susceptibles reported significantly lower pain ratings and kept their hands immersed longer in the cold water than low-susceptible subjects. There were no significant differences between hypnotic and waking condition subjects or between the different strategies. We have discussed the results in terms of a relationship in the literature between choice of experimental design (between-subjects or within-subjects) and the effectiveness of a hypnotic induction for suggested pain reduction. PMID- 2220656 TI - Hypnotic age regression and the autokinetic effect. AB - Based on research with children, we hypothesized that hypnotically age-regressed adult subjects would respond differentially across stimuli conditions on the autokinetic illusion. We assigned 18 highly susceptible subjects, assessed on the Harvard Group Susceptibility Scale, to one of three treatment groups: waking control, standard hypnotic induction, and age regression. Three target shapes, a control stimulus (circle), a representational stimulus (profile of a man), and a symbolic stimulus (cross) were presented. Results failed to show reinstatement of childlike performance on this perceptual illusion. The conceptual and empirical implications for future age-regression studies on memory, perception, and emotion are discussed. PMID- 2220658 TI - Matched group study of preenucleation radiotherapy versus enucleation alone for primary malignant melanoma of the choroid and ciliary body. AB - We report the results of a nonrandomized, matched group survival study comparing 29 patients with a choroidal or ciliary body melanoma managed by enucleation alone to 29 patients managed by enucleation following external beam ocular irradiation (20 Gy in five fractions over 5-7 days just prior to enucleation). Variables on which the patients in the two groups were matched included age at time of enucleation, largest linear tumor dimension, location of the anterior tumor margin relative to the equator and ora serrata, melanoma cell type, and extrascleral tumor extension. The cumulative 5-year survival in the enucleation alone group was 57.9% (SE = 9.9%), whereas that in the preenucleation radiation therapy group was 63.9% (SE = 12.2%). This difference is not statistically significant (p greater than 0.5, Mantel-Haenszel test). The authors discuss the strengths and limitations of their study and the implications of their results. PMID- 2220657 TI - Phase II trial of etoposide, doxorubicin (Adriamycin), and cisplatin (EAP regimen) in advanced gastric cancer. AB - Ten previously untreated patients with gastric cancer were treated with etoposide, 120 mg/m2 intravenously (i.v.) on days 4, 5, and 6, Adriamycin, 20 mg/m2 i.v. on days 1 and 7, and cisplatin, 40 mg/m2 i.v. on days 2 and 8 (EAP). Etoposide, 240 mg/m2 on days 4, 5, and 6, was administered orally instead of intravenously in alternating cycles, and pharmacokinetic studies were performed in those who had previously undergone gastrectomy or who had tumor infiltrating the stomach to determine oral bioavailability. Nine patients had advanced measurable gastric cancer, and one patient had an elevated carcinoembryonic antigen after surgery for synchronous gastric and colon cancer. The median age was 54 years (range 38-69), and the median Eastern Cooperative Oncology Group (ECOG) performance status was 2 (range 0-3). Nine of 10 patients had poorly differentiated adenocarcinoma. Twenty-four cycles were administered to 10 patients, and hematologic data were available for 23 courses. ECOG grade 4 neutropenia and thrombocytopenia developed in 19 (83%) and 8 (53%) courses, respectively. Thirteen courses (54%) were complicated by fever requiring parenteral antibiotics. Two patients (20%) died due to neutropenic sepsis. The profound myelotoxicity observed in our study prompted us to terminate the investigation prior to completing accrual. The oral bioavailability of etoposide was 21% and 36% in the two patients who had had prior gastrectomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220659 TI - Hypercalcemia in head and neck squamous-cell carcinoma. AB - Hypercalcemia was previously considered a terminal phenomenon in advanced head and neck squamous-cell carcinoma. We report on six patients with head and neck carcinoma and hypercalcemia refractory to conventional measures. Three patients had stage IV tumor not amenable to surgery or radiation therapy and three others had carcinoma recurrent after surgery and/or radiation therapy. Five of the six patients had paraneoplastic hypercalcemia and one had extensive bone metastases. One refused chemotherapy and died in 2 months. Five treated with cisplatin 100 mg/m2 i.v. and 5-fluorouracil (5-FU) 960 mg/m2/day x 5, on days 2-7 as a continuous infusion, had prolonged control of hypercalcemia and required no other therapy to maintain eucalcemia. All three patients with no prior therapy, and one of the two patients with recurrent cancer, had a partial response after chemotherapy. The survivals of the patients with recurrent cancer were 1 and 3 months. The survivals in the patients with no prior antitumor therapy were 10, 11+, and 23 months, respectively. In conclusion, hypercalcemia in head and neck carcinoma can be well controlled by cisplatin and 5-FU chemotherapy for a prolonged period. The impact of chemotherapy on survival was minimal in patients with recurrent cancer. In contrast, patients with hypercalcemia at initial presentation of an advanced head and neck cancer have a high likelihood of tumor control and prolongation of survival by chemotherapy. PMID- 2220660 TI - Phase II study of interferon alpha-2a and dacarbazine in advanced melanoma. AB - Based on the report of some activity of combination therapy with dacarbazine (DTIC) and interferon alpha-2a (rIFN alpha-2a) in disseminated melanoma, we conducted a phase II study to determine the feasibility and efficacy in a large series of patients. DTIC was administered in 79 patients at the dose of 800 mg/m2 every 3 weeks and rIFN alpha-2a was given daily at the dose of 9 X 10(6) IU for the first 10 weeks and three times a week thereafter. Among the 75 evaluable patients, 25% achieved an objective response, with 8% complete and 17% partial remissions. The regression occurred within a mean time of 1.9 +/- 1.03 months from starting therapy and the mean duration of response was 8.2 +/- 4.2 months. The major side effects were vomiting, anorexia, fever, fatigue, and myalgia. There was one death related to sepsis after myelosuppression. In the other patients bone marrow and liver toxicities were not remarkable. Our data reveal that a combination regimen of rIFN alpha-2a with a cytotoxic agent has some therapeutic activity in the management of advanced malignant melanoma. PMID- 2220661 TI - A phase II trial of mitomycin in patients with epithelial ovarian carcinoma resistant to cisplatin or carboplatin. AB - Intravenous bolus mitomycin was given at a dose of 10-12 mg/m2 to patients with epithelial ovarian cancer resistant to cisplatin or carboplatin. There were three (12%) partial responses and no complete responses in the 25 patients so treated. PMID- 2220662 TI - Phase II trial of carboplatin in soft-tissue sarcoma. AB - As part of the Eastern Cooperative Oncology Group program for the assessment of new drugs in sarcomas, a Phase II trial of carboplatin was performed in patients who had received no more than one prior chemotherapy regimen. A total of 50 patients received either 400 mg/m2 or 320 mg/m2 depending on whether they had received prior radiotherapy. A response rate of 16% (95% confidence interval 6 32%) occurred in the 37 patients who had received doxorubicin as their only prior systemic therapy. Three of the six responses were complete and persisted for 7 to 34 months. In contrast none of the 13 patients who received carboplatin after initial progression on doxorubicin and subsequent progression on interferon alpha responded. The overall response rate was therefore 12% (95% confidence interval 5 24%). Toxicity was primarily hematologic, with 14 patients having Eastern Cooperative Oncology Group (ECOG) grade 3 toxicity and no grade 4 or 5 toxicities. In view of the number of complete responses, carboplatin should be studied further in untreated patients with advanced soft tissue sarcoma. PMID- 2220663 TI - Solitary brain metastasis: results of an RTOG/SWOG protocol evaluation surgery + RT versus RT alone. AB - From 1983 through 1986, the Southwest Oncology Group and Radiation Therapy Oncology Group conducted an intergroup study designed to evaluate the effectiveness of surgical resection in those patients with solitary central nervous system (CNS) metastases. The study was initially designed as a prospective randomized trial. Because of difficulty accruing patients, the registration format was altered and the patients were placed on study according to physician preference. Ninety-seven patients were registered on study and 80 patients were eventually analyzed. Fifty-five patients underwent radiation therapy alone and 25 patients received surgery and radiation. Fifty-nine percent of those patients undergoing radiation therapy alone improved or stabilized while 79% of those patients undergoing surgery and radiation therapy improved or stabilized. Eventually, 22% of the surgically treated patients failed in the brain while 45% of the patients undergoing radiation therapy exhibited a CNS relapse. Survival was improved when corrected for other prognostic factors in those patients undergoing surgical resection. Although not a prospective randomized trial, this study does suggest an improvement in the survival of a select group of patients able to tolerate neurosurgical resection. PMID- 2220664 TI - Phase II study of oral idarubicin in elderly patients with advanced breast cancer. AB - Thirty-one elderly patients with measurable advanced breast cancer entered this phase II study. A dose of 15 mg/m2/day of Idarubicin (IDA) for 3 consecutive days every 3 weeks was given orally. Mean total cumulative dose of IDA received was 175 mg/m2 (range: 45-475 mg/m2). Mean number of cycles given was four (range: 1 15). Out of 27 evaluable patients, three achieved a complete response (CR), four had a partial response (PR) (CR + PR = 26 +/- 17%), nine showed no change, and 11 had a progressive disease. Median time to progression was 83 days (range: 19-728 days). Out of 26 patients evaluable for toxicity, hematologic toxicity at day 21 was moderate: neutropenia grades 3 and 4 = 16% of cycles: two patients had grade 1 thrombopenia; and three patients, grade 3. No cumulative hematologic toxicity was detected. Nonhematologic toxicities consisted of nausea and vomiting in 72% of patients [World Health Organization (WHO) grades 3 and 4 = 8%)] and alopecia in 76% (WHO grades 2-3 = 38%). Grade 1 stomatitis occurred in 4% of cycles. Chemotherapy was discontinued in one patient because of drop of left ventricular ejection fraction (LVEF) from 0.62 to 0.44 at a cumulative IDA dosage of 322 mg/m2. The results of this study show that IDA is an active drug in elderly patients with advanced breast cancer. Due to its simplicity of administration IDA deserves further investigations in combination with other drugs. PMID- 2220665 TI - Long-term results after chemoradiotherapy for locally confined squamous-cell head and neck cancer. AB - The long-term results after simultaneous chemoradiotherapy in 54 patients with previously untreated or minimally treated, locally confined (M0) squamous-cell carcinoma of the head and neck are presented. Multiple concurrent courses of radiation therapy and chemotherapy with cisplatin and a four-day 5-fluorouracil infusion were given. Twenty-eight patients underwent definitive surgery and 26 were treated without surgical resection. Treatment-associated toxicity was significant, including mucositis, myelosuppression, and a mean 12% loss of initial body weight. Of the 54 patients, 51 were ultimately rendered disease free by this combined modality protocol. With a follow-up ranging from 42-68 months, the projected Kaplan-Meier relapse-free survival for the entire patient cohort is 70%, with all relapses occurring within 17 months of patient entry. The projected Kaplan-Meier relapse-free survival for patients with Stage IV disease is 62%. The durability of these remissions suggests that there is a significant likelihood of cure in all patients with locally confined disease, and justifies comparative trials with standard treatment. PMID- 2220666 TI - A phase I-II trial of continuous-infusion cisplatin, continuous-infusion 5 fluorouracil, and VP-16 in colorectal carcinoma. AB - Twenty-nine evaluable patients with colorectal adenocarcinoma were treated in a phase I-II trial of combination chemotherapy with a 72-h continuous infusion of cisplatin (CDDP) and 5-fluorouracil (5-FU) with an infusion of VP-16 given at 24 and 48 h after the start of therapy. There were five (17 +/- 14%) partial responses lasting 2-6 months (median, 3). Three of these responses occurred among the 10 previously untreated patients. The toxicity of this regimen was pronounced. Four of eight patients with severe neutropenia required hospitalization for infections, two of which were life-threatening; one of six patients with severe thrombocytopenia had a life-threatening hemorrhagic complication; and four patients experienced severe, dose-limiting fatigue. These complications occurred principally with CDDP and VP-16 at doses above 27.5 mg/m2/day and 110 mg/m2/dose, respectively. Mucositis occurred in six patients and limited the dose of 5-FU to 1,300 mg/m2/day. Although the response rate appeared to be high in previously untreated patients, the minimal palliative benefit of treatment and the brief duration of the responses do not compensate for the toxicity observed. PMID- 2220668 TI - Isolation of human immunodeficiency virus (HIV) at autopsy one to six days postmortem. AB - Blood and tissue were studied for potential infectivity at autopsy of ten patients with human immunodeficiency virus (HIV) infection. Special attention was paid to the possibility of detecting HIV in bone at craniotomy. Postmortem intervals were one to six days. Specimens for HIV isolation included skull bone, brain, blood, bone marrow, spleen, and lymph node, and cerebrospinal fluid in one case. HIV grew in culture from at least one specimen from eight autopsies, one of which was performed six days postmortem. HIV was recovered from the blood of five patients and the tissue of five patients, including three with negative blood cultures. Skull bone contained HIV in two cases. HIV also grew from native spleen specimens stored for up to 14 days postmortem at 20 degrees C. Recommended precautions, including those for bone, are indicated at autopsy of HIV-infected patients even after long postmortem intervals. PMID- 2220667 TI - Global and molecular hemostatic markers in acute myeloid leukemia. AB - Patients with acute myeloid leukemia have multiple hemostatic and thrombotic complications, which may or may not result from disseminated intravascular coagulation. Previous studies incorporating routine coagulation analyses failed to detect any clinically useful information in most of these patients. In this study, the first comprehensive evaluation of the various aspects of the hemostatic system in a population of patients with acute myeloid leukemia was performed. Eighteen patients (23-71 years of age) were studied at either diagnosis or relapse. Hemostatic studies were performed at onset and on days 3, 7, and 30 after initiation of therapy. The bone marrow blast counts ranged from 8% to 98%; prothrombin time and activated partial thromboplastin time showed only minor prolongations in a few of these patients. However, in all patients measurement of platelet-associated markers revealed elevated platelet factor 4 and thromboxane B2 and normal 6-keto-prostaglandin F1 alpha levels. Fibrinolytic markers showed an increase in D-dimer and tissue plasminogen activator and a decrease in alpha 2-antiplasmin levels. Plasminogen, plasminogen activator inhibitor, and fibrinogen levels were normal. Coagulation markers demonstrated a decrease in protein C and antithrombin III levels and an elevation of the thrombin-antithrombin complex. The pretreatment values for all hemostatic markers studied were similar to the values obtained on days 3, 7, and 30 during treatment. This investigation demonstrated a subclinical activation of the components of the hemostatic system possibly leading to a hypercoagulable state. Although only six patients (33%) experienced hemorrhagic complications, the risk of bleeding and/or thrombosis was strongly evident in all patients. The significance of finding abnormal levels of specific molecular markers of hemostasis will be established in the future application of such markers in clinical evaluations of leukemic patients known to be at risk for coagulation disorders. PMID- 2220669 TI - Cerebrospinal fluid changes after 48 hours of effective therapy for Hemophilus influenzae type B meningitis. AB - Interval cerebrospinal fluid (CSF) analysis is often performed to assess efficacy of treatment for bacterial meningitis. The authors reviewed 101 cases of pediatric bacterial meningitis resulting from Hemophilus influenzae type b in which analysis of CSF occurred on admission and between 48 and 72 hours after initiation of parenteral antibiotic therapy; of these, only one patient had a positive repeat CSF culture. Of the 100 cases with sterile CSF on repeat culture, there was no instance of recrudescence of infection during hospitalization. The following characterized the interval changes in CSF profile of this group: 100 (100%) with persistence of pleocytosis; 14 (14%) with differential cell count conversion from polymorphonuclear neutrophil leukocyte (PMN) predominance to relative lymphocytosis; 96 of 98 (98%) with initial positive Gram-stained smear with negative results for organisms; 53 of 75 (71%) with normalization of initial hypoglycorrhachia; and 10 of 94 (11%) with normalization of initial abnormally elevated protein levels. The differences in mean values of CSF total white blood cell counts, percentage PMNs, and glucose and protein concentrations on presentation and between 48-72 hours of therapy were highly significant (P less than 0.0001). After 48 hours of effective antibiotic therapy for H. influenzae type b meningitis, CSF pleocytosis and abnormally elevated protein concentration are usually preserved, whereas hypoglycorrhachia usually resolves; it is not uncommon for the differential cell count to convert from a PMN predominance to a relative lymphocytosis. Significant alteration in all CSF parameters associated with H. influenzae type b meningitis can occur after 48 hours of effective parenteral antibiotic therapy. PMID- 2220670 TI - Safety and cost-containment data that advocate abbreviated pretransfusion testing. AB - Abbreviated pretransfusion testing, although permitted by American Association of Blood Banks Standards for unimmunized patients, is not widely practiced. Concerns remain about optimal antibody screening methods, antibodies missed by deleting the antiglobulin crossmatch, and cost-effectiveness. The authors prospectively tested 3,380 serum samples for blood type, antibody screen, and antiglobulin crossmatch. Antibody screens for 2,000 samples, performed with the use of a two cell screen, were compared with 1,380 samples studied with a three-cell screen. Also, all 3,380 sera had major crossmatches performed carried through the antiglobulin phase. Two and three screening cells gave comparable results, with 5.45% of patients tested by two-cell and 5.22% by three-cell screens having a positive antibody screen. Of those with negative screens, 0.5% screened by two cell screens and 0.8% by three-cell screens had a positive major crossmatch. Among these (negative antibody screen, positive crossmatch), only 0.03% (1 of 3.380) had a clinically significant alloantibody (anti-Kpa); 0.27% (9 of 3,380) had antiglobulin crossmatch positive with polyspecific antisera but negative with anti-IgG; and 0.12% (4 of 3,380) had positive crossmatch because of passive anti A. By cost accounting of labor and reagents, 84 per unit would be saved using abbreviated versus complete pretransfusion testing. Blood banks now performing complete pretransfusion testing should reconsider abbreviated crossmatching for unimmunized patients as a safe, efficacious means of cost-containment. PMID- 2220671 TI - The frequency of uterine leiomyomas. AB - As a leading cause of hysterectomy in premenopausal women. uterine leiomyomas are a major public health problem. However, very little work has been done on their epidemiology. Indeed, their true frequency has never been established using systematic and meticulous methods. In this study, gross serial sectioning at 2-mm intervals was applied as an adjunct to routine pathology processing in 100 consecutive total hysterectomy specimens. This tripled the number of leiomyomas noted in routine pathology reports. There were 649 leiomyomas in 77 of 100 uteri, with multiplicity of leiomyomas in 84%. Although leiomyomas were more numerous and larger in women with a clinical diagnosis of myomatous uterus, the incidence was no higher than in uteri removed for other reasons. The postmenopausal incidence of leiomyomas was no lower than the premenopausal incidence, although postmenopausal leiomyomas were smaller and fewer. These findings suggest that epidemiologic studies of leiomyomas may not be valid if they are based only on clinical diagnoses or routine pathology reports. PMID- 2220672 TI - Anaplastic large cell (Ki-1) lymphoma with histiocytic phenotype simulating carcinoma. AB - Histiocytic and epithelial cell types share many cytomorphologic and functional characteristics; it is predictable, therefore, that corresponding malignancies might be difficult to distinguish. Described is the case of a 52-year-old woman in whom disseminated anaplastic large-cell lymphoma simulated carcinomatosis by conventional morphologic criteria. Evidence of histiocytic differentiation was derived from immunocytochemical, fine structural, and genetic probe analyses. The diagnosis of histiocytic neoplasia is discussed in relation to categories previously termed malignant histiocytosis, "Ki-1" lymphoma, and regressing atypical histiocytosis, and comparisons are made with animal tumor models. PMID- 2220673 TI - Primary splenic lymphocyte-depletion Hodgkin's disease. AB - A case of lymphocyte-depletion Hodgkin's disease is described for the purpose of reviewing the criteria currently used to distinguish this disease from other pleomorphic large-cell malignancies. A 76-year-old man with a 3-month history of daily fevers underwent extensive evaluation and exploratory laparotomy, which revealed only two large, separate splenic tumor nodules. Postoperatively, the patient remained asymptomatic. Histologically, the tumor was composed of giant cells, including both typical Reed-Sternberg forms and mononuclear variants with inflammatory stromal response along its borders. Immunoperoxidase showed tumor cells to be strongly reactive for Leu-M1 (CD15), BER-H2 (CD30), Leu-3 (CD4), and T11 (CD2) and weakly reactive for Leu-4 (CD3) but nonreactive for EMA, LCA, lysozyme, Leu-9, Leu-M3, Leu-M5, and immunoglobulin light chains. Southern blot analysis revealed an isolated clonal band for kappa light chain only. Included in the discussion of this case of primary splenic lymphocyte-depletion Hodgkin's disease is a review of clinical, histologic, immunohistochemical, and gene rearrangement characteristics of what can be defined as lymphocyte-depletion Hodgkin's disease. PMID- 2220674 TI - Isolation of measles virus in primary rhesus monkey cells from a child with acute interstitial pneumonia who cytologically had giant-cell pneumonia without a rash. AB - The isolation of measles virus in primary Rhesus monkey kidney cells (PRMK) in patients with documented giant-cell pneumonia who have presented without a rash is limited. The diagnosis usually is made by cytologic examination of nasal or bronchial secretions in which characteristic multinucleated giant cells with intranuclear and intracytoplasmic inclusion bodies are observed. The diagnosis of giant-cell pneumonia has been associated with measles virus but not exclusively. Canine distemper, herpes group viruses, and parainfluenza infections have been associated with these cells. In addition, vitamin A deficiency also has been cytologically associated with multinucleated giant cells. The authors describe the isolation of measles virus from bronchial washing and sputum in PRMK cells at 4 days from an 11-year-old child with acute interstitial pneumonia who was in remission for acute lymphocytic leukemia. Classic cytopathologic effect (CPE) consisting of syncytial and hole formation on the PRMK monolayer was apparent. In addition, a foamy appearance of the monolayer was noted in an otherwise clean lot of monkey cells. Confirmatory testing with measles antibody of the infected areas of the monolayer by indirect immunofluorescence (IFA) was positive for measles antigen and negative for mumps, parainfluenza (types I, II, and III) and influenza A and B virus. Serologic studies for measles antibody revealed an IFA IgG titer of greater than 1:10,240, and an IgM titer of 1:128. Cytologic examination of the same bronchial fluid revealed the typical giant cells with characteristic inclusions associated with measles virus. Because this disease usually is severe, and often fatal, prompt recognition of this virus is essential, not only to the patient, who can be treated with immunoglobulin and/or antiviral therapy, but also to prevent the spread of the virus to other patients and medical personnel. These findings also support direct evidence for the etiologic role of measles virus in giant-cell pneumonia that has been detected either histologically or cytologically and in tissue culture at autopsy. PMID- 2220675 TI - Special report. Immunocytochemistry in diagnostic cytology: a 12-year perspective. AB - In recent years immunocytochemistry has become an important addition to diagnostic cytology. Its routine application in cytology, however, has not yet reached the practical levels it has achieved in diagnostic histopathology. This review examines the values and limitations of immunocytochemistry in diagnostic cytology and addresses some of the most common technical and analytical factors that can affect the outcome of the procedure. PMID- 2220676 TI - Special report. The Second International Anti-cardiolipin Standardization Workshop/the Kingston Anti-Phospholipid Antibody Study (KAPS) group. AB - Forty-three laboratories in 13 countries participated in a workshop to determine the degree of agreement between laboratories performing anticardiolipin tests. Each laboratory received freeze-dried aliquots of three samples labeled G1 (107 GPL units), G2 (20 GPL units), and G3 (6 GPL units) to be used as reference standards in the IgG assay, and three samples labeled M1 (106 MPL units), M2 (21 MPL units), and M3 (5 MPL units) as references for the IgM assay. Participating laboratories were divided into 8 groups and serum samples were exchanged between laboratories in each group. For IgG anticardiolipin, results were reported as: high, IgG positive for samples with optical absorbance readings exceeding G1; medium, IgG positive for samples with readings between G1 and G2; low, IgG positive between G2 and G3, and negative, if less than G3. In like manner, samples were defined as high-, medium-, or low-IgM positive, with reference to standards M1, M2, and M3. An index of agreement was computed to determine the degree of agreement between laboratories in each group. Interlaboratory agreement was excellent in each category assessed. For high positive and negative IgG and IgM results, the index of agreement exceeded 90%, and for medium and low positive results, agreement exceeded 75%. The overall index of agreement between laboratories exceeded 90%. The researchers conclude that the use of these six standards to obtain a semiquantitative measure of anticardiolipin positivity will enable good interlaboratory agreement in reporting anticardiolipin results. PMID- 2220677 TI - HIV and the autopsy. PMID- 2220678 TI - Serum tests for diagnosis of iron deficiency. PMID- 2220679 TI - Ability of whole blood aggregometer to detect platelet hyperaggregability. PMID- 2220680 TI - A diagnostic expert system for colonic lesions. AB - The diagnostic expert system for colonic lesions (DESCL) was designed to discriminate colonic adenoma and adenocarcinoma from normal colonic tissue. Although it was originally developed for use in conjunction with a machine vision analytic system, the DESCL has evolved into a teaching tool and a model for conceptual machine learning. The expert system is table driven and consists of a shell and a knowledge base. The latter comprises a series of architectural and cytologic observations and a quantitative estimate of diagnostic importance relating these observations to diagnostic outcome. In a validation study of 100 colonic lesions, the expert system achieved a success rate of 98%. It has the flexibility to allow individual pathologists to "customize" the knowledge base to suit their diagnostic criteria. PMID- 2220681 TI - ESPRE--expert system for platelet request evaluation. AB - The expert system for platelet request evaluation (ESPRE) is being developed to support independent learning and decision making regarding the use of platelet transfusions while physicians are actively engaged in clinical practice. The knowledge of transfusion medicine incorporated in ESPRE has been largely gathered from blood bank physicians responsible for determining the appropriateness of blood product administration. Knowledge acquisition methods have included structured and unstructured interviews with protocol analysis using real and fabricated transfusion cases and critiques of an expert system prototype's conclusions. For knowledge representation, ESPRE uses frames with embedded production rules to provide processing efficiency and facilitate knowledge base development. ESPRE automatically acquires key laboratory findings from a laboratory information system. Systems such as ESPRE require careful evaluation and, if proven effective and accurate, present to laboratorians a new tool for delivering high-quality and individually adapted health care. PMID- 2220682 TI - Informatics as a separate section within a department of pathology. AB - Departments of pathology should be reorganized to include a separate section of pathology informatics (PI) in addition to the traditional sections of clinical pathology and anatomic pathology. PI is the discipline of medical informatics as practiced within pathology and encompasses a rich mix of activities. The primary role of specialists working in clinical pathology and anatomic pathology would be to create information, whereas that of informaticians in a section of PI would be to add value to the created information by processing it and communicating it to users. The four major benefits associated with a PI section would be as follows: (1) enhanced productivity and efficiency in the development of alignment and impact applications; (2) better management of the information product of pathology and the informaticians themselves; (3) increased political power and influence for pathology; and (4) increased awareness and sophistication on the part of departmental leaders about information processing. Departmental benefits from the proposed organizational change would thus be calibrated in terms of the ability of the revamped department to harness and exploit new information technology. PMID- 2220683 TI - A knowledge-based system for transfusion advice. AB - A knowledge-based system has been designed for evaluating the appropriateness of transfusion of non-red blood cell blood components. The goal of the system is to assist the blood bank physician in quality assurance efforts by automatically identifying cases of inappropriate transfusion before the blood is issued. Evaluation of a working prototype system shows that it is indeed capable of serving this function. The system identifies and summarizes cases, but it leaves consultation, education, and decision making to the blood bank physician. Small "expert systems" such as this may find use in quality assurance activities throughout the laboratory. PMID- 2220685 TI - An interview with Bill Meissner. Interview by Merle A. Legg. PMID- 2220684 TI - Overview of digital imaging in pathology. The fifth wave. AB - During the last decade, pathologists have witnessed dramatic advances in computer hardware and software technology. The major impact of these technologies has been in the management of text information. Significant benefits, however, lie in the manipulation and use of digital images of pathology specimens. Digital images may be analyzed to extract feature information, processed to enhance the visual image, archived to aid diagnostic efforts and education, or transmitted to facilitate communication between pathologists. These components can be integrated with information management systems to form the basis for a work-station for diagnostic pathology. Such technology will likely improve the productivity and diagnostic ability of pathologists in the coming years. PMID- 2220686 TI - Embedding expert systems in laboratory information systems. AB - Expert systems (ESs) may enhance decision making throughout most steps in the clinical laboratory testing process. By embedding ES capabilities in a laboratory information system (LIS), the LIS gains the capability of symbolic reasoning whereas the ES gains use of the LIS database and communications resources. Design considerations include modular integration, performing timely inferences, sparing LIS resources, and providing a syntax that facilitates knowledge base development and verification by laboratorians. The LIS notifies the ES of specimen status changes through an event log. An event scanner finds events that are relevant to prestored knowledge frames and passes this information to an inference processor through instance records. If conditions specified in the knowledge frames are satisfied, an alert processor sends a message to a CRT, printer, file, or report. Examples of applications during order entry, specimen distribution, processing, and results reporting are presented. PMID- 2220688 TI - Has evolution resulted in linear reduction of the jaw? PMID- 2220687 TI - A concern about facial esthetics. PMID- 2220689 TI - An American Board of Orthodontics case report. PMID- 2220690 TI - Trends in sterilization and disinfection procedures in orthodontic offices. AB - The present survey is a repetition of a 1987 survey examining the sterilization/disinfection procedures of Georgia's orthodontists. The purpose of this study is to examine the trends in orthodontic sterilization/disinfection procedures. Orthodontists in Georgia have dramatically changed their sterilization and disinfection procedures. The major changes represented are greater use of protective barrier wear by doctor and staff members; increased heat sterilization methods for instruments, pliers, and handpieces; and increased disinfection of alginate impressions. PMID- 2220691 TI - Coefficients of friction for arch wires in stainless steel and polycrystalline alumina bracket slots. I. The dry state. AB - The surface roughness and the coefficients of friction were measured for sixteen arch wire-bracket combinations. The sample included one rectangular arch wire product from each of the four principal alloy groups and one bracket product from among the stainless steel and polycrystalline alumina inventory. Although subsamples representing both the 0.018-inch and the 0.022-inch slot sizes were evaluated, no differences were observed in their rankings. When tested over a series of eight incident angles, the optical surface roughness of representative stainless steel and alumina brackets averaged 0.148 and 0.193 microns, respectively. After testing at a single angle (82 degree) and referencing a nomogram, the roughness of the stainless steel, cobalt-chromium, beta-titanium, and nickel-titanium arch wire surfaces averaged 0.053, 0.129, 0.137, and 0.247 microns, respectively. When the various arch wire-bracket couples were pressed against an 0.010-inch stainless steel ligature wire at 34 degrees C and otherwise prevailing atmospheric conditions, the coefficients of friction ranged from stainless steel (lowest) to cobalt-chromium, nickel-titanium, and beta-titanium (highest)--regardless of bracket product or slot size. These results corroborated earlier observations in which the same arch wire products were drawn between stainless steel or alumina contact flats. In the current research, the average coefficient of kinetic friction for the stainless steel couple (0.139) was less than that for the stainless steel arch wire against a polycrystalline alumina bracket (0.174). PMID- 2220692 TI - Impact of orthognathic surgery on normal and abnormal personality dimensions: a 2 year follow-up study of 61 patients. AB - The psychological adjustments and self-concepts of 61 orthognathic surgery patients were evaluated before surgery and at 1 month, 6 months, 1 year, and 2 years after surgery. The impact of orthognathic surgery on self-concept and personality adjustment was assessed. Significant improvements in group scores were found with the use of a repeated measures ANOVA in the following subscales of personality disturbances: general maladjustment, psychosis, neurosis, personality disorder, and personality integration. A significantly positive effect was also observed in the following subscales of self-concept: self-esteem, self-satisfaction, self-identity, physical self, family self, social self, and total self-conflict. The improved changes in psychological profile two years after orthognathic surgery are encouraging. PMID- 2220693 TI - Use of cephalometry in diagnosing resonance disorders. AB - A comparative cephalometric study of the oronasopharyngeal dimensions was carried out on 20 patients with normal speech, 20 patients with nasality and 22 patients with cleft palate speech, with the help of cephalometric landmarks given by Proffit and McGlove, Proffit et al., and Ricketts. The data obtained were subjected to statistical analysis, to determine whether there were any significant changes in oronasopharyngeal dimension between the various groups. It was concluded from the obtained data that there was an increase in the width and depth of the nasopharynx, with a consequential increase in the pharyngeal cavity volume in patients with cleft palate speech when compared with patients who had normal speech and those who had nasality. PMID- 2220694 TI - Equilibrium situations in bend force systems. AB - This article provides a simple theoretical approach to the equilibrium situations encountered in biomechanics. Basic differences between the moment of a force and the moment of a couple are described. The concept of the center of resistance is defined and applied to the case of a force system (Rs). Three equilibrium situations are schematically described: the off-center V bend, the centered V bend, and the step bend. Two clinical examples are detailed (one from the Begg technique and one from the Ricketts technique) to demonstrate clinical applications of force in these three situations. PMID- 2220695 TI - Methods used to evaluate growth modification in Class II malocclusion. AB - The methods used to study growth modification in orthodontic patients can have considerable impact on the conclusions that may be drawn. Because of the large "between-patient" variation and small mean changes usually observed, apparent differences in response may sometimes be more attributable to study design than to treatment effectiveness. A systematic review of four major orthodontic journals (1980 to 1987) identified 50 studies reporting treatment of young patients with Class II malocclusion. Variables defined to classify the studies included appliance systems, patient selection, comparison groups, research design, data collection, analysis, and reporting. The appliance systems most frequently investigated were the function regulator and the activator, used with and without headgear. Only 11 (22%) studies were prospective, and random assignment to alternative treatments was never used in this sample. Comparison groups used in 76% of the studies were untreated Class II patients (n = 18) and/or patients with alternate appliance systems (n = 17). In only 24% of the reports were groups tested for pretreatment equivalence. Few studies reported fully how patients had been selected, how decisions had been made to discontinue or change treatment, or whether patients had been lost to study. While most studies reported "p values," in only four were alpha levels adjusted for the number of tests (type I error), and no study included a post beta estimate (type II error). Age, sex, maturation, and duration of treatment were usually reported but seldom adjusted for in the analyses. Given the multiple indices of treatment effect, the generally small sample sizes, weak research designs, and incomplete reporting of important data, we cannot yet conclude whether orthodontic treatment influences the growth of Class II patients. PMID- 2220696 TI - So, how much do orthodontists earn? AB - A review is carried out on available data from the American Dental Association, the Journal of Clinical Orthodontics, and various proprietary publications in an effort to obtain reliable information on orthodontists' income. The results of this study indicate that no definite determination can be made. PMID- 2220697 TI - Appointment in Mostaganem. PMID- 2220698 TI - The American Board of Orthodontics: milestones of progress. PMID- 2220699 TI - Legal aspects of orthodontic practice: risk management concepts. Excellent diagnostic informed consent practice and record keeping make a difference. AB - In this and succeeding issues of the American Journal of Orthodontics and Dentofacial Orthopedics, factual risk management scenarios will be presented. These scenarios are based on composites of actual court cases that have been tried to verdict or decision. Valuable risk management lessons may be learned from careful analysis of the course of the events described. Please be advised that the standard of care determined in any case is specific for that jurisdiction and that set of facts as established by expert testimony for the prevailing party. Readers' comments may be addressed to Dr. Donald E. Machen, 5801 Beacon St., Pittsburgh, PA 15217. PMID- 2220700 TI - Wounding effects of the AK-47 rifle used by Patrick Purdy in the Stockton, California, schoolyard shooting of January 17, 1989. AB - The limited disruption produced in tissue simulant by the rifle and bullets used in the Stockton, California, schoolyard shooting is entirely consistent with the autopsy reports on the five children who died of their wounds. It is also entirely consistent with well-documented battlefield studies and with previous tissue-simulant studies from many laboratories. It is inconsistent with many exaggerated accounts of assault-rifle wounding effects described by the media in the aftermath of this incident. This information should be documented for the historical record. However, the critical reason for correcting the misconceptions produced by media reaction to this incident is to prevent inappropriate gunshot wound treatment. PMID- 2220701 TI - Identification of the driver in two-rider motorcycle accidents. Inguinal contusion-laceration as an indication of the driver. AB - In motorcycle accidents involving two riders, medicolegal identification of the driver is necessary when one or both riders die. It is particularly important in the latter case, because the survivor almost always insists that he or she was not driving. One characteristic injury that distinguishes the driver from the passenger is inguinal contusion-laceration (accompanied internally by pelvic fracture). This injury, caused by collision of the pelvis with the fuel tank, identifies the driver. PMID- 2220702 TI - Atlanto-occipital disarticulation. Accident characteristics. AB - A retrospective study of cases of atlanto-occipital disarticulation was conducted to describe incident characteristics: 24 cases were identified, including nine motor vehicle drivers, two passengers, seven pedestrians, and five motorcyclists; one other person had fallen four stories. The highest rates were found among motorcyclists and pedestrians. Atlanto-occipital disarticulations occur in high energy impacts and collisions and are associated with aortic laceration in 25% and basilar skull fracture in 21% of such cases. Current restraint systems and motorcycle helmets do not appear to prevent this generally rapidly fatal injury. PMID- 2220703 TI - Atherosclerotic cardiovascular disease and sudden deaths among young adults in Wayne County. AB - Based on postmortem records at the Wayne County Medical Examiners' Office from 1982 to 1986, autopsy results indicated that the deaths of 129 persons aged 20-34 resulted from heart disease: 51 of these deaths were attributed to atherosclerotic cardiovascular disease (ASCVD), 29 to hypertensive cardiovascular disease, 28 to cardiomyopathy, and 21 to other cardiac causes. The majority of the deaths due to ASCVD occurred among men, both black and white, followed by black women, and the incidence increased with age. All of these deaths due to ASCVD were sudden and accounted for all deaths due to ischemic heart disease in this age group among Wayne County residents. Diabetes mellitus, left ventricular hypertrophy, a history of seizures, and the recent ingestion of alcohol were all found to be associated with sudden death from ASCVD in this group. Obesity did not seem to be a significant factor. These data suggest that ASCVD is not rare as a cause of death in young adults and some of the risk factors identified in older subjects also operate in this age group. PMID- 2220704 TI - Heart weights of white men 20 to 39 years of age. An analysis of 218 autopsy cases. AB - Review of autopsy data for 218 white men between 20 and 39 years of age who died of injuries or suddenly and unexpectedly indicated a mean heart weight of 371 g. The mean for those dying of external causes was 364 g whereas the mean for those dying of natural causes was 446 g. A coefficient for heart weight expressed as a percentage of body weight was lower in heavy individuals than lightweight individuals; it ranged between 0.38% and 0.55%, with a mean of 0.48%. Heart weight, including epicardial fat, increased with age and body weight. These data may be useful to those who are called upon to investigate sudden and unexpected deaths. PMID- 2220705 TI - Sudden unexpected nocturnal death syndrome in the Mariana Islands. AB - Sudden unexpected nocturnal death syndrome (SUNDS) is a distinct clinical entity in previously healthy, young, Southeast Asian males. It is well known in the Philippines and more recently recognized in the U.S. by nonspecific autopsy findings, with no evidence of underlying disease and absence of toxic drug or alcohol levels. In 1973-89, 14 cases of apparent SUNDS came to coroner's autopsy in the Commonwealth of the Northern Marianas (CNMI) and Guam. All 14 cases, with the exception of one Yapese, were previously healthy, male Filipinos, aged 23 to 55, who were either found dead in bed, or described by their colleagues as having nocturnal seizure activity consisting of gurgling, frothing, and tongue biting immediately prior to death. Autopsy findings showed no anatomic findings to account for death. Comprehensive serum and urine drug analyses were negative. All decedents showed absence of significant atherosclerosis or grossly detectable structural cardiac anomaly, while four showed cardiomegaly. Migrants from Southeast Asia carry with them a pre-disposition to this syndrome, which appears to decline with longer residence in the new country. The mechanism of death in SUNDS is believed to be ventricular fibrillation, possibly precipitated by sudden sympathetic discharge. Studies suggest at least some deaths may be associated with an abnormal cardiac conduction system. Acute pancreatitis has been a finding in some series, but not our cases. Why the condition is virtually limited to males and seemingly sleep-triggered, has not been adequately explained. Stress and depression are believed to be predisposing factors. PMID- 2220706 TI - Fatal big cat attacks. AB - Two cases of fatal attacks by large cats are presented. In the first case, a 30 year-old female zoo worker was attacked by a jaguar that had escaped its cage. In the second case, a 2-year-old girl was fatally injured by her father's pet leopard. The pattern of injuries in these cases is nearly identical to those of these cats' prey in the wild. PMID- 2220707 TI - Cardiac conducting tissue. A simplified technique for examination of the SA and AV nodes. AB - We describe a modified method for examination of the atrioventricular and sinoatrial nodes that displays the major elements of the cardiac conducting system, yet is not time-consuming for the technician. We examined 31 cases in three categories: cases with previous cardiac history, sudden deaths from no known cause, and cases where death was sudden and accidental. All cases showed histologic abnormalities in the cardiac tissue. We contend that our method would permit such examination to be routinely used in the pathology laboratory. PMID- 2220708 TI - Arsenic poisoning: acute or chronic? Suicide or murder? AB - The case of the death by arsenic poisoning of a 62-year-old white man is presented. One year prior to death, he developed intermittent bouts of severe gastroenteritis with vomiting and diarrhea, hyperpigmentation and keratosis of the skin, neutropenia, and Guillain-Barre-like neuropathy for which he was hospitalized several times. Urine test results 6 months prior to death indicating 36 mg/L arsenic were believed to be in error. At the patient's last admission, he appeared in the emergency room with severe gastroenteritis, hypotension, and dehydration. He died 3 days later. Antemortem as well as autopsy specimens revealed elevated arsenic concentrations. Arsenic micrograms/g analysis by neutron activation of hair pulled from the man's head revealed by centimeter segmental analysis proximal to distal: 226, 104, 28, 56, 41, 40, and 74. The wife of the decedent was charged with murder by arsenic poisoning of this, her fifth, husband. The defense alleged that the decedent had committed suicide. The judge awarded a directed verdict of "not guilty." Particulars of the medical, toxicological, and investigative findings are presented. PMID- 2220709 TI - Can dentists recognize their own work? The forensic implications. AB - After 10 months, 71.4% of a group of dental students were able to recognize amalgam restorations that they had placed in the mouths of manikins. After 24 months, 57.1% of the group were able to recognize their work again. In contrast, only 5.5% of a second group of students, who did not have the interim viewing at 10 months, could recognize their work at 24 months. These results suggest that, with time, dental operators lose the ability to recognize their work but that this ability is prolonged by interim observations of the work. This study underscores the need for dentists to chart and record accurately any artifacts introduced into the patient's mouth, as well as any features that would make the patient unique upon forensic examination. PMID- 2220710 TI - Accidental death from a black-powder rifle breech plug. AB - Authentic black-powder muzzle-loader weapons and replicas are used today primarily for hunting game such as deer and hogs. The following is a case presentation of accidental death from cerebral trauma caused by a .45-caliber black-powder-rifle breech plug implanting in the victim's brain. PMID- 2220711 TI - Path of bullet and injuries determined by radiography. AB - Radiography is commonly used to find bullet pathways in forensic pathology. In the case presented here, a man had sustained multiple gunshot wounds and one bullet could not be traced. A radiograph was used to find the bullet and showed an interesting bullet pathway. By observing the bullet pathway on a radiograph, sometimes we can surmise the victim's body posture at the time of an incident. PMID- 2220712 TI - Identification of the driver in an automobile collision. AB - We report on a three-occupant automobile collision in which one of the two survivors claimed that the deceased had operated the vehicle. We attempted to identify the driver. The left face and neck of the deceased appeared to have struck the vehicle's interior. The survivors were slightly injured on the right side of their faces. In Japan, the passenger side is on the left, and in this case, the right side of the vehicle had been damaged. By comparing the injuries of the deceased and the survivors in relation to the vehicle damages, we concluded that the deceased occupant had probably been a passenger, not the driver. PMID- 2220713 TI - Fatal high cervical spinal cord injury in an automobile accident complicating os odontoideum. AB - We report a case where spinal instability from incomplete fusion of the dens of C2 (os odontoideum) allowed anterior displacement of the skull and first cervical vertebra following right frontal impact against the A pillar in an automobile accident. Resultant crushing and laceration of the spinal cord occurred at the level of C1 and C2. Without either radiographic investigation or detailed examination of the spine, the fatal injury might have been overlooked and death attributed to acute alcoholic poisoning because the blood alcohol level was .613%. PMID- 2220714 TI - Thymic hyperplasia. A clue to the diagnosis of hyperthyroidism. AB - The association of simultaneous abnormalities of the thyroid and thymus is well documented, particularly in the case of Graves' disease. We present a case of a natural death following thyroid storm in which marked thymic hyperplasia was present. This finding can be helpful in determining the cause of death. PMID- 2220715 TI - Sudden death due to right ventricular cardiomyopathy. AB - A 21-year-old man died suddenly at a small party. He had had no clinical signs of cardiac disease except for a slightly abnormal electrocardiogram (occasional premature ventricular contractions) since he was 15 years of age. Autopsy examination revealed cardiomegaly (469 g), with right atrial and ventricular dilatation. The right ventricular myocardium was massively replaced with adipose tissue, and there was one isolated fatty lesion in the right side of the ventricular septum. There were no congenital malformations such as a septal defect or valvular deformity. Histologically, muscular fibers remaining in the right ventricular wall showed neither degenerative nor inflammatory changes. An isolated lesion of the ventricular septum consisted of almost complete replacement of the muscle bundles with adipose tissue. Such a pathologic condition has recently been termed right ventricular cardiomyopathy. Postmortem examination is necessary to make a definite diagnosis of the disease, because in most adult cases of the disease, sudden death occurs before there have been any critical signs. PMID- 2220716 TI - Forensic medicine in Hong Kong. A personal view. PMID- 2220717 TI - Medical examiner office management using the personal computer. The Fulton County experience. PMID- 2220718 TI - Sudden death due to delayed rupture of hepatic subcapsular hematoma following blunt abdominal trauma. AB - Blunt abdominal trauma can cause sudden, unexpected death due to injuries to internal organs. Rupture of a hepatic subcapsular hematoma is a relatively rare cause of sudden death following minor blunt abdominal trauma. Death may be delayed several days to weeks. The autopsy is an invaluable diagnostic tool that can be utilized to uncover sudden deaths due to abdominal trauma. The case of an alcoholic who died of a ruptured hepatic subcapsular hematoma is presented. The death investigation revealed that the victim had sustained blunt abdominal trauma during a fall a few days prior to death. PMID- 2220719 TI - Clinical significance of colonic fermentation. AB - Recent evidence of the potential benefits of short chain fatty acids has prompted renewed interest in the area of human colonic fermentation. This paper reviews the clinical and metabolic consequences of colonic fermentation. PMID- 2220720 TI - Is brief arterial oxygen desaturation during endoscopy dangerous? PMID- 2220721 TI - Arterial oxygen desaturation during gastrointestinal endoscopy. AB - This prospective study evaluated the incidence and severity of arterial oxygen desaturation during gastrointestinal endoscopy. Following pulmonary function testing, 115 male patients underwent esophagogastroduodenoscopy (EGD), colonoscopy, or colonoscopy followed by EGD, with continuous recording of arterial oxygen saturation (SaO2). Most patients (80/115, 70%) showed arterial oxygen desaturation (greater than 4% decrease from baseline SaO2); severe arterial oxygen desaturation (SaO2 less than or equal to 85%) reflecting hypoxemia (PaO2 less than or equal to 50 mm Hg) was noted in one-third of patients overall (37/115, 32%). Severe arterial oxygen desaturation occurred in 9/62 EGD patients (15%), 23/46 colonoscopy patients (50%), and 4/7 patients having colonoscopy followed by EGD (57%). Arterial oxygen desaturation occurs frequently during gastrointestinal endoscopy and is often severe. These data support the concept that continuous monitoring of SaO2 should be standard procedure during all gastrointestinal endoscopic procedures. PMID- 2220722 TI - Prospective randomized comparison of Brown-McHardy and microvasive balloon dilators in treatment of achalasia. AB - We report the results of a randomized prospective study comparing a standard bougie rubber balloon dilator [Brown-McHardy (BMH)] and a newer polyethylene dilator passed over a guide wire [Microvasive Rigiflex (MVR)]. Twenty achalasia patients (15M, 5F, mean age 45.4 yr) considered candidates for either dilator were randomized. Symptom assessment, body weight, and upright radionuclide solid esophageal emptying study were measured before and 6 months after pneumatic dilatation. All dilatations were performed by one of three experienced gastroenterologists under fluoroscopic guidance. Overall success occurred with 10/10 BMH and 7/10 MVR. One patient not improved with MVR had myotomy; the other two were successfully treated by BMH. No complications occurred with either dilator. PMID- 2220723 TI - Features distinguishing secondary achalasia from primary achalasia. AB - Eighteen patients with cancer-induced or secondary achalasia (SA) were compared to 421 patients with idiopathic or primary achalasia (PA). The aim of the study was to detect any differences in clinical presentation between the two groups. Mean age of patients with SA was 57.1 (range 15-78) and 47.1 (range 1-90) in patients with PA (p = 0.02). Three patients with SA were 15, 24, and 36 yr old, respectively. Symptom frequency was comparable in SA versus PA. Mean duration of symptoms in SA was 4.5 months, with 15 of the 18 patients experiencing symptoms for six months or less. Weight loss occurred in 88.2% of patients with SA and 57.3% of patients with PA (p less than 0.05). Cancer was at the gastroesophageal junction in 16 patients, duodenum in one, and breast in one. Endoscopy showed tumor in 12 (67%). The esophagram was suspicious for tumor in only 25%. We conclude that patients with SA are older, more likely to lose weight, and have a short duration of symptoms. However, SA may occur in younger patients, and endoscopy with biopsy is necessary in any newly diagnosed case of achalasia. PMID- 2220724 TI - Healing or amelioration of esophagitis does not result in increased lower esophageal sphincter or esophageal contractile pressure. AB - There is conflicting evidence regarding whether lower esophageal sphincter and esophageal contractile pressures are affected by changes in the severity of gastroesophageal reflux disease. We compared the manometric and endoscopic findings from 30 patients before and after treatment for esophagitis. Before treatment, the grade of esophagitis (I-III) was significantly correlated (r = 0.37; p less than 0.05) with lower esophageal sphincter pressure, but not with esophageal contractile pressure. After treatment, the grade of esophagitis did not change or became worse in 15 patients, and became better in 15 patients. Of these, seven healed. The group that showed no endoscopic improvement demonstrated no change in lower esophageal sphincter or esophageal contractile pressures. The group that did show endoscopic improvement also demonstrated no increase in lower esophageal sphincter or esophageal contractile pressures, and this was particularly evident in those whose esophagitis healed. These data suggest that healing of esophagitis does not result in improvement of esophageal motor function. PMID- 2220725 TI - Sucralfate used as adjunctive therapy in patients with severe erosive peptic esophagitis resulting from gastroesophageal reflux. AB - A total of 36 patients with grade 2 or greater erosive esophagitis and an abnormal 24-h pH monitor study, were treated in a randomized, double-blind fashion to assess the efficacy of sucralfate suspension as adjunctive therapy to cimetidine for severe esophagitis secondary to gastroesophageal reflux. Treatment consisted of cimetidine, 300 mg qid and either sucralfate suspension (1 g/10 ml) or an identical placebo suspension, 10 ml after meals and 20 ml hs. Patients were treated for 12 wk unless endoscopic healing occurred earlier. Initial evaluation and monthly follow-up consisted of symptom monitoring, endoscopic evaluation and pre- and post-therapy esophageal manometry, Bernstein test, and 24-h pH monitoring. The combination of cimetidine and sucralfate suspension was superior to cimetidine alone in improving daytime heartburn symptoms (p less than 0.05) but not nighttime heartburn, dysphagia, or regurgitation. Sucralfate plus cimetidine improved the overall endoscopic outcome of esophagitis more than cimetidine alone (p less than 0.05). More patients exhibited endoscopic healing in the adjunctive sucralfate group than in the cimetidine-only group. Endoscopic healing, however, was not statistically different between groups. We conclude that sucralfate used as adjunctive therapy to cimetidine resulted in improvement of some of the symptoms of reflux, and probably increases the likelihood of complete healing of esophagitis, compared with cimetidine alone. PMID- 2220726 TI - Comparison of coffee intake and coffee-induced symptoms in patients with duodenal ulcer, nonulcer dyspepsia, and normal controls. AB - Coffee and decaffeinated coffee stimulate acid secretion. In addition, many patients experience dyspepsia after coffee ingestion. Therefore, coffee is often prohibited by physicians in patients with peptic diseases. However, the association between peptic disease and symptoms remains unclear. This study compares coffee intake and the induction of symptoms by coffee in patients with duodenal ulcer disease, nonulcer dyspepsia, and normal controls. We have studied the coffee drinking habits of 58 duodenal ulcer patients, 55 nonulcer dyspepsia patients, and 55 normal controls. The use of coffee on a daily basis was not significantly different between duodenal ulcer patients (64%) and controls (56%), or between nonulcer dyspepsia patients (55%) and controls. There was also no difference between the three groups in the use of decaffeinated coffee, the number of cups per day, the method of preparation, the length of time of coffee use, or any change in coffee intake in the previous year. The intake of tea, caffeinated carbonated beverages, and aspirin or nonsteroidal anti-inflammatory drugs was also similar in the three groups. The duodenal ulcer patients were more likely to be cigarette smokers (45%) than either the controls (16%) or the nonulcer dyspepsia patients (24%). Daily alcohol intake was not significantly different in the three groups. The prevalence of coffee induction of dyspeptic symptoms was similar in duodenal ulcer patients (29%) and controls (22%), but was much more common in nonulcer dyspepsia patients (53%) than in controls (22%), p = 0.0036. In conclusion, there was no difference in coffee intake between patients with duodenal ulcer, nonulcer dyspepsia, or normal controls. However, patients with nonulcer dyspepsia, but not duodenal ulcer, were more likely to experience dyspeptic symptoms after coffee ingestion. PMID- 2220727 TI - Duodenal ulcer hemorrhage with and without dyspepsia. AB - To clarify the clinical significance of dyspepsia in patients with bleeding duodenal ulcer, we studied 298 patients prospectively. Ages of patients ranged from 16 to 81 yr (mean 45.9). There were 244 (82%) dyspeptic and 54 (18%) nondyspeptic patients. In the dyspeptic group, significantly more patients were taking nonsteroidal anti-inflammatory drugs. In the nondyspeptic group, there was a higher percentage of patients with duodenal bulb deformity (p less than 0.005), which deformity was related to previous peptic ulcer disease. The age, sex, past history of dyspepsia or bleeding, consumption of alcohol and cigarettes, and the hospital course of the two groups of patients did not differ significantly. Our results show that the clinical course of duodenal ulcer hemorrhage is not significantly different in patients with or without dyspepsia, and indicate that bleeding and dyspepsia probably are two independent presentations in the natural course of the disease. The significance of the correlation between dyspepsia and duodenal bulb deformity is discussed. PMID- 2220728 TI - Liver pathology in morbidly obese patients with and without diabetes. AB - The contribution of obesity and/or diabetes to liver pathology in the morbidly obese patient is controversial. We studied the liver biopsies of 100 consecutive patients undergoing gastric bypass surgery for morbid obesity. Multiple morphologic parameters were analyzed and graded independently, without knowledge of the clinical history, liver function tests, and oral glucose tolerance results of the patients. Six percent of the entire group demonstrated no fat, 42% mild fat, 20% moderate fat, and 24% severe fatty metamorphosis of the liver. Twenty three percent of the patients had central vein fibrosis, 23% sinusoidal fibrosis, 19% bridging fibrosis, and 4% cirrhosis. Thirty-six percent of the patients had some degree of steatohepatitis, 66% possessed so-called glycogen nuclei of hepatocytes, 6% had PAS-positive thickening of blood vessels in the portal tracts, and 1% had lipogranulomas. The degree of fatty metamorphosis and fibrosis was analyzed in three separate groups, categorized by the glycemic status of the patient: 46 patients with normal glucose tolerance (NGT), 23 patients with impaired glucose tolerance (IGT), and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM). Increasing severity of fatty metamorphosis from the normoglycemic obese to the diabetic obese patients was found, which was statistically significant by chi 2 analysis. Four of the six patients showing no fatty metamorphosis were normoglycemic. Glycogen nuclei and PAS-positive blood vessels were significantly more prevalent in the diabetic obese than in the normal obese. In conclusion, the distribution of significant liver histopathology in the morbidly obese patient correlates in severity with the degree of impaired glycemic status. PMID- 2220730 TI - Percutaneous transhepatic cholecystostomy for acute complicated cholecystitis in elderly patients. AB - We report our experience with percutaneous transhepatic cholecystostomy in 10 elderly patients with acute cholecystitis, complicated by empyema formation. Most of these patients has severe underlying disease, rendering them at high risk for surgical intervention. In all patients, the percutaneous procedure was followed by a rapid regression of clinical symptoms and of radiologic abnormalities. Six were considered inoperable. Three of these remain free of biliary symptoms, respectively 22, 10, and 7 months after percutaneous cholecystostomy. Three others died of nonbiliary disease 1-4 months after cholecystostomy. Three patients underwent successful elective cholecystostomy 1-5 wk after percutaneous cholecystostomy. In one patient, cholecystectomy had to be performed because of recurrence of hydrops, 1 wk after catheter removal. In our opinion, percutaneous transhepatic cholecystostomy is a safe and effective procedure in the treatment of elderly patients with acute complicated cholecystitis. It can be followed by elective cholecystectomy in good surgical candidates, or by an expectant conservative management in high surgical risk patients. PMID- 2220729 TI - Factors influencing the development of metabolic bone disease in primary biliary cirrhosis. AB - The prevalence, type, and factors that may influence the development of bone disease in primary biliary cirrhosis, have been investigated in 20 consecutive patients, who, in addition to liver function tests and mineral and vitamin D metabolism studies, were submitted to a transiliac bone biopsy after tetracycline double-labeling for quantitative histomorphometric examination. Intestinal calcium absorption was also assessed in 16 patients. Seven patients (35%) had reduced bone volume and were considered osteoporotic. Three also had bone mineralization impairment, but did not have criteria for osteomalacia. Bone formation was depressed in 15 patients, and bone resorption was low or normal in 19 cases. Eroded surfaces were reduced in all osteoporotic patients. Duration of primary biliary cirrhosis was significantly longer in patients with osteoporosis (6.3 +/- 0.6 yr) than in those without osteoporosis (2.6 +/- 0.6, p = 0.004). Moreover, osteoporosis was more prevalent in postmenopausal women, and in those who had intestinal calcium malabsorption, which was present in 80% of osteoporotic patients but in only 18% of nonosteoporotic patients (p = 0.03). Osteoporosis and mineralization bone impairment were unrelated to the severity of cholestasis. 25-Hydroxyvitamin D was significantly lower in those patients with intestinal calcium malabsorption. The results of this study indicate that osteodystrophy in primary biliary cirrhosis is characterized mainly by "low turnover" osteoporosis, which is related to the duration of the liver disease, postmenopausal condition, and calcium malabsorption. PMID- 2220732 TI - Comparison of a new immunoassay for determining serum pancreatic isoamylase with two standard techniques. AB - A method has recently been developed for measuring serum pancreatic (P) isoamylase, using two monoclonal antibodies specific for salivary isoamylase. We performed this test on 67 healthy controls and 133 patients: 15 with acute pancreatitis, 53 with chronic pancreatitis (20 during painful relapse and 33 in clinical remission), 18 with pancreatic cancer, 41 with nonpancreatic disease with abdominal pain, five with macroamylasemia, and one with total pancreatectomy. Results were compared with those of a wheat germ inhibition method and with electrophoresis on cellulose acetate. A close correlation was found between the results of immunoinhibition assay and those of the other two tests. All patients with acute pancreatitis had abnormally high values in all three tests. In the group with chronic pancreatitis studied during painful relapse, 16 had an increase in P-isoamylase, as determined with the immunoinhibition assay, 13 with the wheat germ inhibition test, and 15 with electrophoresis. In the group with chronic pancreatitis in clinical remission, we found low values in one patient, by immunoinhibition assay, but found low values in 17 and 19 patients by wheat germ inhibition and electrophoresis, respectively. Low P-isoamylase values corresponded to a severe exocrine pancreatic insufficiency. In the group with pancreatic cancer, the three tests showed similar results, and the majority of the patients had normal values. In the patients with nonpancreatic diseases, abnormally high levels were found in five, by immunoassay, in four by electrophoresis, and in three by the wheat germ inhibition method. In the five cases with macroamylasemia, both inhibition assays erroneously demonstrated an abnormal P-isoamylase elevation. The results show that the three tests are equally useful for the diagnosis of acute pancreatitis, or chronic pancreatitis during an acute relapse. In these diseases, the immunoinhibition test would be the preferred assay because it is simple and rapidly performed. PMID- 2220731 TI - Comparative studies of DU-PAN-2, carcinoembryonic antigen, and CA19-9 in the serum and bile of patients with pancreatic and biliary tract diseases: evaluation of the influence of obstructive jaundice. AB - The levels of DU-PAN-2 antigen, carcinoembryonic antigen, and CA19-9 in serum and bile of patients with pancreatic and biliary tract diseases were measured. The sensitivities (true positive) of DU-PAN-2 in serum to pancreatic carcinoma (64%) and to biliary tract carcinoma (62%) were similar to those of CA19-9 in serum (69% and 72%, respectively). Nine of 18 (50%) patients with CA19-9-negative pancreatic carcinoma tested positive for DU-PAN-2. The sensitivities of CEA to pancreatic carcinoma (56%) and to biliary tract carcinoma (52%) were lowest. The measurement of these antigens in bile seemed to be of little diagnostic value in differentiating between malignant and benign diseases. False positives of these three assays occurred frequently in patients with benign pancreatic or biliary tract disease coupled with obstructive jaundice. After percutaneous transhepatic biliary drainage, serum DU-PAN-2 and CA19-9 levels returned to normal ranges in patients with benign diseases, but not in patients with carcinoma of the pancreas or of the biliary tract. Serum CA19-9 and DU-PAN-2 antigens are useful tumor markers for pancreatic and biliary tract carcinomas. Longitudinal assays of these antigens may be useful for the differential diagnosis of patients with obstructive jaundice. PMID- 2220733 TI - In vivo evaluation of monopolar versus bipolar electrosurgical polypectomy snares. AB - The energy required and tissue damage in bipolar and monopolar polypectomy snares were compared in a canine model. The bipolar snare required an average of 34 joules of energy, whereas the monopolar snare required 228 joules to cut the same diameter of gastric mucosa tended into a polypoid structure (p = 0.0005). The reduced energy delivered to the tissue from the bipolar procedure resulted in only 32% average depth of damage to the underlying gastric wall, whereas the monopolar procedure caused an average 69% (p = 0.001). Surgically created polyps required 247 joules and 69 joules for corresponding monopolar and bipolar polypectomy (p = 0.001). The decreased energy required and the correspondingly reduced damage caused to the underlying bowel wall by the bipolar snare should reduce the incidence of perforation and post-polypectomy syndrome. The bipolar snare completes a local circuit about the snare, eliminating the return electrode and, consequently, the possibility of any return electrode burns. The bipolar snare thus provides an added safety margin during polypectomy. PMID- 2220734 TI - Endoscopic ultrasonography in staging rectal cancer. AB - Endoscopic ultrasonography (EUS) was used to stage rectal cancer by assessing depth of invasion through bowel wall layers and/or involvement of lymph nodes. EUS findings were correlated with histopathologic findings to discern the usefulness of this modality in predicting which patients could be candidates for sphinctersaving procedures and the avoidance of abdominoperineal resection. The Olympus EU-M3 endoscopic ultrasound system was used to assess depth of penetration through rectal wall layers and to identify lymph nodes. Comparison of EUS findings to histopathologic findings was possible in 13 patients. EUS agreed with histopathology in 9 of 13 cases (69.3%) ( p = 0.07, kappa statistic). EUS agreed with histopathology as the presence or absence of lymph nodes in 9 of 13 cases (69.3%) (p = 0.07). However, the presence of lymph nodes could not necessarily predict metastatic involvement of these nodes. In one patient, invasion of vaginal cuff was correctly predicted. In nine cases, computed tomographic analysis (CT) was available for comparison to EUS in detection of penetration beyond the bowel wall. CT agreed with histopathology in 3 of 9 (33%), whereas EUS agreed with histopathology in 7 of 9 (78%). PMID- 2220736 TI - Protein-losing enteropathy in systemic lupus erythematosus associated with intestinal lymphangiectasia. AB - This case report concerns a young woman with systemic lupus erythematosus who presented with a protein-losing enteropathy. Intestinal biopsy revealed lymphangiectasia. Mesenteric lymph nodes showed paracortical lymphoid depletion and multiple small sinusoids. Elevated cholesterol levels and normal lymphocyte counts characterized the peripheral blood samples. Lymph nodes, though enlarged, showed no evidence of obstructive pathology. No secondary cause of lymphangiectasia could be identified. The patient exhibited antinuclear antibodies and antibodies to dsDNA at the onset, and then, 5 yr later, the classic features of systemic lupus erythematosus (SLE). The lymphocytopenia and hypolipidemia that characterizes lymphangiectasia is not a feature of the SLE cases reported to date. Furthermore, the mechanism for the dilated lymphatics and villous edema is more likely immunological than mechanical disruption of lymphatics. PMID- 2220735 TI - Hyperplastic gastric polyps associated with persistent Helicobacter pylori infection and active gastritis. AB - We report two cases of patients with 3-yr histories of upper gastrointestinal symptoms, hyperplastic gastric polyps, and active chronic gastritis. Biopsies retrospectively stained with Giemsa revealed the persistent presence of Helicobacter pylori (HP) in gastric biopsies of both patients throughout the 3 yr. After treatment with amoxicillin and bismuth subsalicylate, both became asymptomatic, one demonstrating disappearance and recurrence of the gastric polyps in conjunction with the HP. These cases demonstrate 3 yr of hyperplastic gastric polyps associated with HP and active gastritis. PMID- 2220737 TI - Gallbladder carcinoma producing human chorionic gonadotropin. AB - A primary carcinoma of the gallbladder producing human chorionic gonadotropin (HCG) was encountered in an 83-yr-old Japanese woman, with elevation of HCG/beta HCG in urine and serum. Remarkable elevation of serum estradiol was an associated finding, with increased HCG. At autopsy, we found that the primary carcinoma of the gallbladder extensively involved the liver. Histologically, the tumor revealed adenosquamous cell carcinoma in the primary site, and moderately to poorly differentiated adenocarcinoma in metastatic foci. Immunohistochemical staining for beta-HCG showed a positive reaction in adenocarcinoma components. This is an extremely rare case of an HCG-producing gallbladder carcinoma, which leads us to speculate that HCG-positive tumor cells may occur due to dedifferentiation. PMID- 2220738 TI - Isolated ventral pancreatitis in a patient with pancreas divisum. AB - A previously healthy 22-yr-old woman was found to have chronic pancreatitis restricted to the ventral pancreas in association with pancreas divisum. When conservative treatment failed, sphincteroplasty of both papillae was performed with good results. This well-documented case represents a clear exception to the commonly held concept that obstruction of the dorsal duct is the essential pathogenic factor in the development of pancreatitis associated with pancreas divisum. The importance of visualizing both the dorsal and ventral pancreatic ducts to direct therapy for patients with idiopathic pancreatitis is discussed. Theories of the pathogenesis of concomitant pancreatitis and pancreas divisum are reviewed. PMID- 2220739 TI - Hepatic giant cavernous hemangioma with microangiopathic hemolytic anemia and consumption coagulopathy. AB - We describe a case of hepatic giant cavernous hemangioma with both microangiopathic hemolytic anemia (MAHA) and consumption coagulopathy, but without thrombocytopenia, which was completely cured by surgical resection of the tumor. The patient was a 54-yr-old Japanese woman whose chief complaint was right upper abdominal discomfort. Angiography and dynamic computed tomography revealed typical findings of hepatic cavernous hemangioma. The patient also had hematological disorders. At surgery, we performed an atypical right lobectomy to preserve as much normal liver tissue as possible. The patient has been well, with no related complaints or abnormal laboratory findings, 5 yr since her operation. This case indicates that giant cavernous hemangioma of the liver should be considered in the differential diagnosis of MAHA, and if surgical treatment is adequate, hematological abnormalities may be eliminated. PMID- 2220740 TI - Exacerbation of chronic active hepatitis type B after short-term corticosteroid therapy resulting in fatal liver failure. AB - The case of a 36-yr-old male with chronic active type B hepatitis in whom 4-wk prednisone therapy resulted in prolonged and fatal exacerbation of liver disease is described. Thus, short-term corticosteroid therapy may in some patients have disastrous effects on the course of chronic active hepatitis B. PMID- 2220741 TI - Toxoplasmic chorioretinitis and hepatic granulomas. AB - A 71-yr-old male presented with a 2-month history of fever, malaise, and weight loss. Physical exam revealed chorioretinitis. Laboratory studies were notable for elevated levels of alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate transaminase, and alanine transaminase. Immunoglobulin G antibody to Toxoplasma gondii was positive to a dilution of 1:4096, whereas serologic studies for hepatitis A virus, hepatitis B virus, cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus, Brucella, and Tularemia were negative. A percutaneous biopsy of the liver revealed hepatic granulomas. Culture of the biopsy specimen was negative for growth of mycobacteria or fungi. Spontaneous improvement in clinical and laboratory parameters occurred over a 4-month period. PMID- 2220742 TI - Disseminated, nonmeningeal gastrointestinal cryptococcal infection in an HIV negative patient. AB - Gastrointestinal cryptococcosis is extremely rare, especially in patients with no involvement of the central nervous system. We describe a 63-yr-old man undergoing prednisone therapy for chronic hepatitis and cirrhosis who presented with peritonitis, colitis, and skin lesions. Pathological studies revealed necrosis and numerous cryptococcal organisms in the colon, omentum, and skin, and cultures yielded Cryptococcus neoformans. The patient died of multisystem organ failure following emergency exploratory surgery performed when he had onset of symptoms of a bowel perforation after an endoscopic biopsy. Clinicians should be aware that gastrointestinal cryptococcosis can occur in the absence of infection of the central nervous system or lungs, and that it may affect relatively healthy patients who are immunocompromised because of splenectomy, chronic liver disease, or steroid therapy. PMID- 2220743 TI - Prognosis in acute pancreatitis: an alternative to Ranson's criteria. PMID- 2220744 TI - Predictors of variceal bleeding: solving the puzzle. PMID- 2220745 TI - Chronic pancreatic pain: cut for cure? PMID- 2220746 TI - Onions and dyspepsia. PMID- 2220747 TI - Pneumatosis cystoides intestinalis after cardiac transplantation: report of three cases. PMID- 2220748 TI - Gastric carcinoma presented as cardiac tamponade. PMID- 2220749 TI - Endoscopic diagnosis of esophageal tuberculosis. PMID- 2220750 TI - Nocardia brasiliensis peritonitis in a patient with AIDS. PMID- 2220751 TI - Colonoscopic identification of "Crohn's carcinoma" of the ileum. PMID- 2220752 TI - Intravascular hemolysis following endoscopic variceal sclerotherapy. PMID- 2220753 TI - Disaccharidases in duodenal biopsies in Helicobacter pylori-positive patients. PMID- 2220754 TI - Incipient papillary cystic tumor of the pancreas. PMID- 2220755 TI - Acute abdomen in drug addicts: think of blunt trauma. PMID- 2220756 TI - Platelet derived growth factor messenger RNA is increased in bone marrow megakaryocytes in patients with myeloproliferative disorders. AB - Platelet derived growth factor (PDGF) has been suggested to play an important role in the pathogenesis of myelofibrosis, which often occurs in patients with myeloproliferative disorders (MPD). We examined the expression level of PDGF mRNA in bone marrow megakaryocytes from 13 MPD patients by in situ hybridization, using cDNA probes for both human PDGF A chain and B chain (c-sis). The mRNA level for both chains in the patients was significantly higher than that in control patients, and was markedly higher for one patient with essential thrombocythemia and one with polycythemia vera. Transcripts for A chain and B chain were expressed with a positive correlation in the MPD patients. Using the marrow fibroblast proliferation assay, we found PDGF activity in purified megakaryocytes from one of the MPD patients with high mRNA level to be similar to that from one control patient. In addition, PDGF was previously shown to be decreased in circulating platelets from MPD patients. These results may suggest that, in some patients, PDGF is synthesized in megakaryocytes at a high rate, but some fraction is released into the bone marrow environment, if the level of PDGF mRNA is assumed to be linearly related to the protein synthesized. This might be one possible mechanism causing marrow fibrosis in MPD patients. PMID- 2220757 TI - Proliferation and differentiation of erythroid progenitors in liquid culture: analysis of progenitors derived from patients with polycythemia vera. AB - We have recently described a new two-phase liquid culture that supports the development of human erythroid progenitors (Fibach et al., Blood 73:100, 1989). The procedure separates the erythroid burst-forming units (BFUe) from the erythroid colony-forming units (CFUe) stage and enables quantitation of the proliferation and differentiation of BFUe into CFUe. In the present study we have utilized this system to study erythroid progenitors in polycythemia vera (PV). The abnormality of the erythroid series in PV has been shown to be associated with an increased responsiveness of the progenitors to the hormone erythropoietin (Epo). A basic question in this clonal stem cell disorder is at what developmental stage this abnormality of the PV clone is phenotypically expressed. We have studied this question by comparing the development of Epo-dependent and Epo-independent CFUe from peripheral blood BFUe of the PV patient during the BFUe to CFUe transition in the liquid culture. The results indicated that both types of CFUe are generated and that in all cases tested the ratio of Epo-independent progenitors at both the BFUe and CFUe stage was similar indicating no preferential development of Epo-independent CFUe. These results suggest that the abnormality of the PV erythroid progenitors is expressed only at the CFUe level. Moreover, since the liquid culture did not contain Epo, the results also support the conclusion that BFUe do not require Epo for proliferation or differentiation into CFUe. PMID- 2220758 TI - Identification of p70 and p80 associations with class II MHC molecules and Ii. AB - Two proteins, p70 and p80, were found in chemically crosslinked complexes with class II MHC molecules and Ii after 3-12 hr labelings with [35S]methionine. Two dimensional, nonreduced/reduced SDS gel electrophoresis of immunoprecipitated complexes revealed 1) endogenous disulfide linkages between Ii-Ii and Ii-p70 and 2) chemically crosslinked, nearest neighbors of alpha-beta, alpha-Ii, Ii-p70, and alpha-p80. Although such nearest neighbors within multimeric complexes were identified as dimers in nonreduced/reduced 2D gels, stoichiometries could not be determined in the high molecular weight complex(es), which included alpha, beta, Ii, p70, and p80, and were not separated in the first dimension. p80 was not the chondroitin-sulfate form of Ii (Ii-CS) because it was not electrophoretically heterogeneous and was not sensitive to chondroitinase ABC. p70 was not hsp72/74 detected with C92 or N27 mAbs, and p80 was not BiP detected with its respective mAb. While only these two proteins associated prominently with class II MHC antigens and Ii late after synthesis, their functions are unknown. PMID- 2220760 TI - Efficacy of the high molecular weight fraction of plasma for the maintenance of pregnancy associated with thrombotic thrombocytopenic purpura. AB - We have investigated the methods for the maintenance of a pregnancy in a patient with thrombotic thrombocytopenic purpura (TTP), said condition, since 1984, having been controlled by a plasma infusion every 3 to 4 weeks. In a preliminary trial it was confirmed that an infusion of the high molecular weight fraction (HMW-F) of plasma, separated by an Evaflux 2A fractionator, improved the patient's thrombocytopenia as the plasma infusion, and maintained its beneficial effect for about 2 weeks during early pregnancy. Though an occurrence of a toxemia-like syndrome responded to repeated plasma infusion, the dose of plasma required to improve the thrombocytopenia gradually increased and reached 5,040 ml by the 20th week of pregnancy. Thus, instead of periodic infusions of whole plasma, periodic infusions of the HMW-F of plasma were used. Under this regimen the platelet count remained above 10.0 x 10(4)/microliters during late pregnancy, and the total dose (2,600 ml) of HMW-F of plasma that was administered until delivery at full term was less than the dosage of whole plasma that was used during early pregnancy. In this manner we were able to obtain a healthy baby by controlling the patient's TTP during pregnancy. This method of preventing thrombocytopenia appears to be safer with respect to volume loading during pregnancy in the TTP patient. PMID- 2220759 TI - Selective reduction of serotonin storage and ATP release in chronic renal failure patients platelets. AB - Hemorrhagic complications, as monitored by skin bleeding times, occur in a significant number of chronic renal failure (CRF) patients. The etiology of hemostatic defects in these patients is complex and ill defined. Our studies demonstrate, for the first time, that activated platelets, derived from CRF patients, release significantly (P less than .001) less ATP than controls while the percent of releasable serotonin (5HT), assumed to be co-stored with ATP, is unaltered. Analysis of the CRF-derived platelets reflects a selective acquired storage pool defect with significantly (P less than .001) reduced 5HT levels while their dense granule contents of ATP and ADP are normal. The comparison of ATP release from platelets derived from CRF patients whose bleeding times were less than 9 min to those with bleeding times of 9 min or greater was significantly different (P less than .02). This report demonstrates for the first time that there is a statistically significant correlation of ATP release and 5HT content to bleeding times (P less than .001). The perturbation of platelet 5HT uptake, 5HT dense granule content, and ATP release appears to result from newly described altered plasma factors, detected by our in vitro mixing studies. It is proposed that the reduced level of releasable platelet 5HT and ATP contributes to bleeding disorders commonly encountered in CRF patients. PMID- 2220761 TI - Leukocyte depletion filters: a comparison of efficiency. AB - Four commercially available leukocyte depletion filters were evaluated using a flow cytometric technique to determine the efficiency of each type of filter. The Sepacell R-500A and the PALL RC50 were the most efficient in leukocyte depletion having a mean depletion percentage of 99.3% and 99.5%, respectively. The PALL RC100 which is used for two units also had a 99.3% depletion with the first unit but with the second unit the depletion dropped to 94.2%. The imugard IG-500 had a 97.3% depletion. Red cell recovery ranged from 87.4% for the PALL RC50 to 92.2% for the Sepacell R-500A. PMID- 2220762 TI - Diagnosis of pyruvate kinase deficiency in a transfusion-dependent patient with severe hemolytic anemia. AB - In a 2-yr old girl a hemolytic anemia was present since birth requiring multiple blood transfusions. Pyruvate kinase deficiency was suspected on the basis of a marginal enzyme activity, but could not be established due to the presence of massive numbers of donor cells in her peripheral blood. However, by density fractionation we succeeded in the isolation of a small fraction of the patient's own cells, in which a severe pyruvate kinase deficiency could be detected. In contrast hexokinase and glucose-6-phosphate dehydrogenase activities were extremely high, which is indicative that a very immature cell population is present in this fraction. In immunofluorescence studies a clear crossreaction was apparent with anti M2-type pyruvate kinase antibodies, whereas only a faint reaction with anti L-type could be detected. Despite the presence of a slight amount of L-type immunoreactive material, the residual activity in the patient's cell fraction could only be attributed to M2-type pyruvate kinase as was shown by cellulose acetate electrophoresis. PMID- 2220763 TI - New treatment strategies for multiple myeloma. AB - During the past 5 years, several new treatments and strategies have been developed for patients with multiple myeloma. For patients with disease resistant to standard therapies, these include the VAD regimen, dexamethasone alone, high dose melphalan, and intensive chemoradiotherapy with bone marrow transplantation. Alpha interferon appears to have its greatest potential as part of early induction therapy or during remission maintenance. The role of hemopoietic growth factors or blood stem cells in support of high-dose therapy and drugs that may overcome multiple drug resistance continues under study. A sequence of non-cross resistant therapies early in the disease course seems worthy of investigation, especially in patients at high risk for early relapse. PMID- 2220764 TI - Neonatal alloimmune thrombocytopenic purpura associated with sensitization against the platelet-specific antigen Yuk(a). AB - We report a Japanese newborn who developed alloimmune thrombocytopenia by the antibodies to the newly discovered platelet antigen Yuk(a). The infant recovered uneventfully in 10 days without specific treatment. Antiplatelet alloantibodies in the patient were IgG class detected by mixed passive hemagglutination (MPHA). Family study showed that Yuk(a) antigen was inherited as an autosomal dominant trait. Cases with Yuk(a)-associated alloimmune thrombocytopenia are reviewed. PMID- 2220765 TI - Disseminated intravascular coagulation and hemorrhage in hemophilia B following elective surgery. AB - Two patients with hemophilia B are described in whom disseminated intravascular coagulation (DIC) developed following infusion of repeated doses of Factor IX concentrate in the perioperative period. In both cases the surgery was elective, Factor IX survival studies had been done to assure proper dosing, and Factor IX levels were monitored daily. Neither patient had clinically significant liver disease. The DIC manifested itself as excessive blood loss from surgical drains without documented thrombosis and was accompanied by prolonged coagulation times, increased fibrin split products and decreased fibrinogen and platelets. In both patients the process was quickly reversed with administration of fresh frozen plasma, cryoprecipitate, and the addition of heparin to the Factor IX concentrate. These cases highlight the difficulty in managing patients with hemophilia B undergoing surgical procedures due to the potential thrombogenicity of the currently available concentrates, and the importance of differentiating the bleeding associated with DIC from underdosing with Factor IX. Furthermore, the potential complications associated with the presently available Factor IX concentrates stress the need for the development of purer, safer Factor IX concentrates. PMID- 2220766 TI - Congenital factor XIII deficiency associated with von Willebrand disease. AB - A boy with umbilical bleeding and severe hemorrhages after minor trauma, without family bleeding history, was studied. Coagulation tests showed abnormalities in FXIII subunits and FVIII/vWF complex. Both parents presented results compatible with a heterozygote state for FXIII deficiency and the father had abnormalities of FVIII/vWF. The propositus was diagnosed as congenital FXIII deficiency associated with vWD. No severe hemorrhagic complication was observed after a prophylactic regimen with cryoprecipitates. PMID- 2220767 TI - Acute myocardial infarction, non-bacterial thrombotic endocarditis, and disseminated intravascular coagulation in a severe hemophiliac. AB - Thrombosis in hemophilia is very rare and is usually associated with the administration of prothrombin complex concentrates. We describe a severe hemophiliac with P. carinii pneumonia who had clinical and laboratory evidence of acute myocardial infarction and disseminated intravascular coagulation, and at autopsy, nonbacterial thrombotic endocarditis as well. We suggest that prothrombin complex concentrates should be used cautiously in the setting of acute infection, and perhaps be given with appropriate doses of anticoagulants such as heparin. PMID- 2220768 TI - Ph chromosome in a patient with non-leukemic non-Hodgkin B-cell lymphoma. AB - A standard Philadelphia translocation, t(9;22) (q34;q11), was found in lymph node cells from a patient with non-leukemic non-Hodgkin lymphoma at the time of diagnosis. The rearrangement of the breakpoint cluster region (bcr) was not detected with a bcr-3' probe. The neoplastic clone was of monoclonal B-cell character with E-, CD5-, CD10-, CD13-, CD19+, CD20+, CD21+, CD25-, HLA DR+, and positive surface Ig(kappa). The patient showed no evidence of chronic myelogenous leukemia. PMID- 2220769 TI - FAB L3 type of B-cell acute lymphoblastic leukemia (B-ALL) without chromosome abnormalities. AB - Acute lymphocytic leukemias (ALLs) are morphologically classified into L1, L2, and L3. The former two types are phenotypically constituted of quite heterogeneous ALLs. In the present study, phenotypes of cells from five L3 type ALL were analysed in FACS-IV using a panel of monoclonal antibodies (MAbs). The leukemic cells of all these patients coexpressed la (HLA-DR), CD19, CD20, CD21, CD24, CD38, and surface immunoglobulins, whereas a negative reaction with MAbs CD1, CD2, CD3, CD4, CD7, CD8, and Ti (WT31), Ti gamma A, delta TCS 1, and anti TCR-gamma/delta was observed. Neither myeloid-monocyte-erythroid nor megakaryocyte related cell surface antigens were detected in these cases with L3 type ALL. Chromosomal analysis of the ALL cells from two cases revealed a normoploid karyotype with specific translocation t(8;14)(q24;q32), whereas it was normal (46XY or 46XX) for the remaining three cases. Expression of myc oncogene was high in the former group, but low in the later one. Basing from our findings, we conclude that L3 type ALL is heterogeneous with respect to immunophenotypes, cytogenetics and oncogene analysis. PMID- 2220770 TI - Overview: renal physiology and pathophysiology of aging. AB - Cross-sectional studies in humans have suggested that there is a progressive decline of renal function with age after 40 years. The decline in various functions (eg, tubular maximums, concentrating and diluting abilities, and acidification) tend to parallel the decreases in glomerular filtration rate (GFR) and renal blood (plasma) flow (RPF). Recent observations from the Baltimore Longitudinal Study of Aging suggest that not all individuals follow this pattern, and that, indeed, many show no decline and some even an increase in their renal function over time. Whether the observed decreases in renal function with aging are the results of intervening pathologic processes, eg, immunologic, infectious, and toxic injury and ischemia, or can be related to hyperperfusion and hyperfiltration with resultant glomerulosclerosis, or to some other relentless involutional process, remains unclear. The purpose of this report is to review the descriptive studies documenting the changes in renal morphology and physiology with age and to discuss what is known about mechanisms involved in these losses of renal substance and function. PMID- 2220771 TI - Geriatric pharmacokinetics and the kidney. AB - The general population is aging and, as a result, drugs are increasingly prescribed for a variety of medical conditions in a group of patients with multiple physiologic and pharmacokinetic abnormalities. The present report summarizes principles of prescribing for the elderly, especially those related to the decline in renal function that frequently occurs. PMID- 2220772 TI - Nutritional causes of renal impairment in old age. AB - The occurrence of renal insufficiency tends to increase in late adulthood. This common complication of old age is associated with increased physical dependency, morbidity, and mortality, and a lowered quality of life. In this review, the authors will develop the thesis that dietary practices during early and middle adulthood importantly influence the risk of renal insufficiency in the elderly. PMID- 2220773 TI - Hyperkalemia in the elderly. AB - Physiologic and pathologic events that occur in patients as they grow older may result in distal renal tubular dysfunction, as well as decreased levels of plasma renin activity and plasma aldosterone. Such alterations result in a tendency toward hyperkalemia. A syndrome termed hyporeninemic hypoaldosteronism, associated with hyperkalemia, has been frequently described in elderly patients. The common occurrence of hyperkalemia in the elderly may be aggravated by the use of drugs that either further suppress renin and/or aldosterone or interfere with distal tubular potassium excretion. Some patients with hyporeninemic hypoaldosteronism respond to diuretic therapy. The recognition of the possible development of severe hyperkalemia in the elderly patient may avoid serious and even fatal complications of this electrolyte disorder. PMID- 2220774 TI - Renal disease in the elderly: the role of the renal biopsy. AB - The causes of renal disease in the young and the elderly vary in their frequency. There are many indications for renal biopsy in older patients, with the nephrotic syndrome (NS) being the most common, followed by acute renal failure. Biopsy does not carry a greater risk for older patients, but there is a greater risk of complications when there is coexistent renal insufficiency. Interpretation of the renal biopsy in elderly patients may be more complex because of changes associated with aging or intercurrent disease--arteriolar sclerosis and global sclerosis. A prospective study is needed to determine the exact prevalence of renal insufficiency, NS, and other renal diseases in noninstitutionalized elderly individuals and to determine the role of renal biopsy in making these determinations. PMID- 2220775 TI - Treatment of glomerulonephritis in the elderly. AB - Glomerular disease was assessed in persons who had renal biopsies and who were age 60 years and older in retrospective reviews of referral-based cohorts in Europe, the United States, and Japan. From a cumulative total of 514 patients reported from five centers, 337 (66%) patients had primary glomerular diseases and 177 (34%) had various secondary renal diseases. Amyloidosis was the largest histopathologic group among the secondary disorders. Idiopathic membranous nephropathy was the most common primary glomerulopathy (107/337 [32%] patients) and also comprised 46% of nephrotic patients. In our experience covering two consecutive 13-year periods from 1959 to 1984, there was an increase both in total number of patients, and in percentage more than 60 years old, with membranous nephropathy in the more recent study period compared with the earlier period reflecting a trend to more biopsy procedures that included older patients. Non-immune-mediated rapidly progressive glomerulonephritis (RPGN), thought by some to be more common in older adults, has been shown to represent a crescentic glomerulonephritis associated with systemic necrotizing vasculitis. Treatment with corticosteroids had a short-term favorable effect on renal function in this disorder over that achieved in antiglomerular basement membrane-associated or idiopathic RPGN. However, the 5-year patient survival was remarkably lower in older patients irrespective of the disease entity. On the other hand, age was not associated with progressive renal failure in patients with membranous nephropathy. Finally, minimal change glomerulopathy accounted for 35 of 204 (17%) nephrotic subjects, and complete remissions occurred after corticosteroid treatment at the same frequency (80% to 90%) observed in younger patients. PMID- 2220777 TI - Basic evaluation of female urinary incontinence. AB - Urinary incontinence is a common disorder that is frequently underreported because of its social implications. Although several types of urinary incontinence are recognized, they can be generally classified as failure of the bladder to store or failure of the urethral mechanism. A systematic approach for the evaluation of incontinence that includes history, physical examination, basic laboratory tests, and often urodynamic evaluation, offers the most comprehensive assessment of the etiology of incontinence. PMID- 2220776 TI - Geriatric diabetic nephropathy: an analysis of renal referral in patients age 60 or older. AB - We report a series of 33 consecutive hospitalized geriatric diabetic patients who were referred for evaluation of diabetic nephropathy, defined as proteinuria greater than or equal to 1 g/d (1,000 mg/24 h) or a serum creatinine concentration greater than or equal to 177 mumol/d (greater than or equal to 2 mg/dL). The study population was 60 years old or older (mean age, 68 +/- 6 years), was comprised mainly of women (24 of 33, 72.7%), and was predominantly black (25 of 33, 75.8%). All patients had type II diabetes. A family history of diabetes in parent or sibling was elicited in 24 (72.7%) patients. There were eight patients undergoing maintenance hemodialysis and 25 with less severe nephropathy (mean proteinuria, 2.7 g/d [2,700 mg/24 h]; mean creatinine clearance, 0.57 mL-s [34 mL/min]). Cardiac disorders were noted in the majority of patients: congestive failure in 20 (60.6%), myocardial infarction in eight (24.2%), and active angina in five (15.2%). Other comorbid diseases were present in both hemodialysis patients and the subset of nondialyzed azotemic-proteinuric patients, and consisted of peripheral neuropathy in 31 (93.9%), gastroparesis in 16 (48.5%), retinopathy in 28 (84.8%), and legal blindness in 11 (33%). We conclude that geriatric diabetic nephropathy in type II diabetes is similar in presentation and severity of comorbid extrarenal complications to the syndrome described in younger adults. This inference must be tempered by both the small size and the limitation imposed by the demographics of the study population, which is predominantly composed of black patients receiving treatment at inner city hospitals. PMID- 2220778 TI - Bladder dysfunction in the elderly. AB - Bladder dysfunction in the elderly is an enormous public health problem. Laboratory research using animal models has to date not yielded clinically useful new information. Demographic and urodynamic studies in selected elderly patients indicate that neurological disease and bladder outlet obstruction are the primary causes for voiding dysfunction. The effect of aging per se on the urinary bladder is not known. Elderly patients who have bladder dysfunction should be evaluated with a careful history and physical examination combined with a practical urodynamic evaluation rather than simply being labeled as having "bladder dysfunction in the elderly." PMID- 2220779 TI - Genitourinary cancer in the elderly. AB - The subject of genitourinary cancer in the elderly becomes increasingly more important as our population of patients older than 50 years expands. Carcinoma of the kidney, bladder, and prostate all have an increasing incidence over the age of 50 and have a predilection for afflicting men more commonly than women. Etiologic factors, especially with bladder and kidney carcinomas, are well documented and in some cases preventable. Screening the urine for hematuria and careful digital rectal examinations may uncover a higher percentage of these malignancies in earlier, more curable stages. Recent advances in the treatment of all of these malignancies have improved survival and quality of life for these patients. PMID- 2220780 TI - Treatment of renal calculi in the elderly. AB - The management of renal calculi in the geriatric patient population poses some unique problems that include anesthetic risks, underlying medical disease, and general risk/benefit concerns. A variety of relatively noninvasive procedures are available, including extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrostolithotomy (PCNL). A practical management plan is presented that is based primarily on stone size and takes into consideration problems unique to the elderly patient. PMID- 2220781 TI - Systolic hypertension in the elderly: reasons not to treat. AB - Isolated systolic hypertension in the elderly is associated with increased morbidity and mortality. Accurate measurement of blood pressure in older patients is difficult. Therapy can be associated with various complications, and the special problems of the elderly, such as orthostatic hypotension and hyperkalemia, should be carefully considered. Drugs should be used in low doses and changes in dosage should be made infrequently. Patients should be monitored frequently for untoward effects of therapy. The benefits of blood pressure reduction and the optimal degree of blood pressure reduction remain unknown. PMID- 2220782 TI - Peritoneal dialysis in the geriatric patient. AB - Elderly patients on chronic peritoneal dialysis (CPD) from two large chronic peritoneal dialysis programs were compared with younger patients in regard to peritonitis rates, catheter problems, hospital days, transfers to other forms of therapy, and mortality. Peritonitis rates and organisms were similar in younger and older patients. Catheter replacements were less common in the elderly. Differences in hospital days were attributable to hospitalization for vascular disease. The elderly were more likely to have the first episode of peritonitis, to die and to change dialysis modalities at all times after the first year of continuous ambulatory peritoneal dialysis (CAPD) treatment, although other than increased mortality, differences between the two groups were small. CPD appears to be an acceptable form of renal replacement therapy in the elderly. PMID- 2220783 TI - Hemodialysis and the elderly patient: potential advantages as to quality of life, urea generation, serum creatinine, and less interdialytic weight gain. AB - A total of 204 patients treated by maintenance hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) were studied to ascertain how advancing age influences adaptation to uremia therapy. No difference in Karnofsky score was noted among patients over 70 years of age and two groups of patients, 16 to 59, and 60 to 69 years of age, respectively. In a subset of 33 hemodialysis patients studied midweek, it was noted that increasing age is associated with a lower serum creatinine concentration, lower interdialytic weight gain, and a lower urea generation rate. These three findings contribute to a relative ease in treating older uremia patients with hemodialysis or CAPD, as they tend to be stable and compliant relative to younger patients. PMID- 2220784 TI - The elderly on dialysis: some considerations in compliance. AB - Compliance with scheduled treatments, dietary and fluid restrictions, and multiple medications is an important component in the care and well-being of end stage renal disease (ESRD) patients. Given the rigorus and complex demands of dialysis, it is important to examine the issue of compliance, focusing on a large and ever-increasing segment of our patient population, the elderly. The ESRD literature reflects efforts to define and measure levels of compliance, identify factors that influence and predict compliance, and develop intervention strategies to improve adherence to treatment regimens. While limited attention has been focused specifically on the elderly, there are studies suggesting that age may be a factor associated with improved adherence and that social support may be a significant contributor to compliance in this patient group. In an effort to examine the current status and needs of the dialysis elderly, research is in progress at Chromalloy American Kidney Center, Washington University, which replicates a study of 5 years ago. Eighty-four patients age 60 and over, on dialysis for a minimum of 6 months, were identified. Sociodemographic, treatment, compliance, and functional capacity data were collected; additional mental and psychological testing was completed on patients willing and able to participate. Preliminary data suggest the current elderly population is larger and significantly older than that of 5 years ago. Other sociodemographic data indicate the population is increasingly female, black, and more socioeconomically disadvantaged. In regard to compliance, the vast majority of elderly demonstrate good compliance as measured by serum potassium, fair to good compliance with phosphorus, and fair to poor compliance with fluid restrictions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220785 TI - Strategies for enhancing compliance in the dialysis elderly. AB - Noncompliance must be viewed as a symptom of another problem or problems. Treatment plans should be developed based on an individualized assessment of the patient's physiologic functioning and psychosocial situation. It must be determined whether the patient is intentionally or unintentionally not complying. Staff must also be aware of how they impact compliance. While staff have a responsibility to maximize the individual's efforts to comply, it must be realized that the ultimate decision and responsibility rests with the patient. PMID- 2220786 TI - Principles of geriatric care. AB - The increase in the numbers of elderly in the United States, and their projected continued increase to 21% or more of the population by 2030, has provided impetus for the growth of geriatrics. Recognition of change that is age-related rather than disease-related, and the ways in which the elderly differ from their young counterparts is vital in the care of the elderly. A functional approach and appropriate geriatric assessment have been shown to be beneficial to the individual. PMID- 2220787 TI - Prevention of renal disease and conservation of renal function. AB - In summary, we have reviewed some of the most frequently encountered areas of prevention of renal failure in the elderly. They include obstruction, hypertension, drug interaction, and inappropriate use of drugs and the silent killer of the elderly, renal carcinoma. Only by a thorough understanding of the altered physiology of the aging kidney can the physician avoid making the same mistakes when new drugs are developed or new types of diseases are encountered. Proper early diagnosis and understanding the guidelines to therapy in these conditions, can save huge human costs in terms of mortality, morbidity, and money. PMID- 2220788 TI - Ethical issues in geriatric nephrology: overview. AB - Developments in medical care over the past five to six decades have provided remarkable life-sustaining technologies (LST) that have contributed to prolongation of the life span of patients, as well as to a general increase in health and well-being. End-stage renal disease (ESRD) treatment is a prototype of these LST treatments and of the issues surrounding provision of chronic/catastrophic care. This remarkable progress has been accompanied by ethical dilemmas that include allocation of scarce resources, and initiation and termination of care with LST. Consideration of these ethical dilemmas are especially poignant for the elderly, because they raise "hard choices" and there are no easy answers to these ethical dilemmas. PMID- 2220789 TI - Ethical principles in geriatric nephrology. AB - Seven principles are suggested to resolve ethical issues raised by medical developments affecting an aging society. First, there must be clear identification of the goals of medical treatment. Second, treatments must consider the whole person. Third, physiological concerns are more important than chronological age. Fourth, a patient's choice must be respected when choice is the result of an informed decision-making process. Fifth, access has to be equitable while respecting the sixth principle which requires allocation of resources. Finally, society must more clearly identify the appropriate principles to guide the care of the dying person. PMID- 2220790 TI - Ethical and legal issues in geriatric nephrology. AB - Ethical and legal issues affecting geriatric nephrology are conditioned more by individuals' status as elderly, sick people than by the distinctive characteristics of kidney disease or failure. Key ethical issues are the obligation to respect persons, in particular by recognizing competent persons' autonomy of medical choice and affording due protection to dependent or vulnerable individuals, by beneficence or doing good, and by acting with justice, treating like cases alike and avoiding unjust discrimination. The law reinforces ethical obligations through such legal concepts as informed consent and the duty to maintain appropriate confidentiality, which have special applications concerning medication and management of the elderly. Additional legal issues concern advanced care directives and terminal care decisions. PMID- 2220791 TI - High technology health care. AB - High technology medicine often harms more people than it saves. The resources that are spent in too many of our high technology procedures could be far more effectively used to save far more lives in other parts of the system. High technology health care is thus a blessing and a curse. It is a blessing if it is used correctly, but tragically it is too often a curse, stealing resources desperately needed elsewhere. PMID- 2220792 TI - Rationing of health care and the end-stage renal disease program. AB - The potential impact of rationing health care on the end-stage renal disease (ESRD) program is considered. The possible implications of the recommendations emanating from the study being conducted by the Institute of Medicine of the National Academy of Sciences are also mentioned. Particular emphasis is given to the potential consequences of rationing health care on the elderly and on certain socioeconomic groups with ESRD. PMID- 2220793 TI - Looking upon the water: taking in the students. PMID- 2220794 TI - The renal cardiac connection: pieces of the puzzle. A symposium held in conjunction with the annual meeting of the American Society of Nephrology. December 1989, Washington, D.C. Proceedings. PMID- 2220795 TI - Effects of calcium antagonists on renal hemodynamics. AB - Recent attention has been 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 actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do markedly alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment the glomerular filtration rate but produce only a modest improvement in renal perfusion. Studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, have demonstrated that the augmentation of the glomerular filtration rate is attributable to a preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations are not fully delineated, preliminary studies in experimental animal models indicate that calcium antagonists might exert salutary effects on renal function in clinical settings characterized by an acute impairment of renal hemodynamics. It is apparent, however, that the renal hemodynamic effects of calcium antagonists commend their use in the management of essential hypertension. PMID- 2220796 TI - Calcium channel blockers versus angiotensin-converting enzyme inhibitors: renal effects. AB - Angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers are two classes of antihypertensive agents with novel effects on renal function. In both experimental and clinical studies, calcium channel blockers tend to increase renal blood flow, glomerular filtration rate, and urinary sodium excretion in essential hypertension. ACE inhibitors have similar effects on renal blood flow and glomerular filtration rate in essential hypertension, but they tend to cause sodium retention. ACE inhibitors can cause marked reductions in glomerular filtration rate in renovascular hypertension, making them a problematic choice for the treatment of this form of hypertension. In chronic, progressive renal diseases, ACE inhibitors have been shown to decrease protein excretion and morphologic evidence of glomerulosclerosis. The relationship of the decrease in protein excretion to the progression of renal disease has not yet been established. PMID- 2220797 TI - Diabetes mellitus and hypertension. AB - Hypertension and diabetes mellitus are chronic medical conditions that frequently coexist. In the United States, it is estimated that 10 million persons suffer from diabetes mellitus, 60 million from hypertension, and 3 million from the combination of the two. There may be a causal relationship between hypertension and diabetes. Obesity may be a precipitating factor for both hypertension and non insulin-dependent diabetes mellitus. Those with insulin-dependent diabetes mellitus generally become hypertensive only with the onset of nephropathy. Glucose tolerance, insulin resistance, and hyperinsulinemia frequently occur with essential hypertension and may be aggravated by hypertension therapy, especially with diuretics and beta-blockers. Hyperinsulinemia may be an important common factor promoting sodium retention, sympathetic nervous system stimulation, and inhibition of the sodium pump. The Working Group on Hypertension in Diabetes has outlined a flexible modified version of the stepped-care approach to the treatment of hypertension in diabetes. Management is complex because diabetes is associated with autonomic neuropathy, sexual dysfunction, hyperlipidemia, and fluid and electrolyte disorders. All these problems can be exacerbated by antihypertensive treatment. Nonpharmacologic measures, which address weight reduction and sodium restriction, are logical, but aggressive antihypertensive medication is invariably necessary. Diuretics and/or beta-blockers were the mainstay of treatment until the introduction of angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. These newer agents have no deleterious effects on carbohydrate metabolism and are generally better tolerated. Antihypertensive therapy may slow the rate of deterioration in diabetic nephropathy. This was first shown with diuretics, beta-blockers, and hydralazine and more recently with ACE inhibitors, which provide effective blood pressure control and a significant drop in albuminuria without affecting the glomerular filtration rate adversely. ACE inhibition may also lead to increased insulin sensitivity and glucose disposal rate. Long-term trials are needed to assess the effects of these new agents on the treatment of hypertension in the diabetic population. PMID- 2220798 TI - Calcium channel blockers and atherosclerosis. AB - Several chemical classes of calcium channel blockers (CCBs) inhibit atherosclerotic lesion formation in rabbit models by reduction of calcium, lipid, and matrix accumulation in the arterial wall. The mechanisms of these antiatherogenic effects are under investigation. Smooth muscle cells and macrophages, which synthesize matrix products and accumulate intracellular lipids, play a central role in lesion formation. Smooth muscle cell hyperplasia, with intracellular and functional changes, is common to both atherosclerosis and hypertension. The antiatherogenic properties of CCBs may be related in part to the protection of arterial cells from calcium overload through inhibition of calcium flux across voltage-regulated ion channels. CCBs may also inhibit cell migration, influence the uptake and catabolism of lipoproteins, alter smooth muscle matrix synthesis, and promote the depletion of intracellular cholesteryl ester stores. It appears that CCBs may inhibit the development of atherosclerotic lesions by two sets of mechanisms: alteration of lipid metabolism in smooth muscle cells and regulation of calcium-initiated or -accelerated intracellular processes. PMID- 2220799 TI - Hypertension: racial differences. AB - Racial differences in the prevalence, course, and pathophysiologic characteristics of hypertension in black and white populations are reviewed. Accumulated epidemiologic data indicate that the prevalence of hypertension among blacks is greater than that among whites in almost all age- and sex-matched groups. Hypertensive blacks have a higher incidence of left ventricular dysfunction, stroke, and renal damage, but a lower incidence of ischemic heart disease, than do hypertensive whites. A significant pathophysiologic difference between blacks and whites is salt sensitivity; normotensive, as well as hypertensive, blacks tend to be salt sensitive. Blacks also tend to have lower renin levels than do whites, while dopamine response to a salt load is diminished among blacks as compared with whites. These differences and others lead to the recommendation that hypertension among blacks should be managed initially with salt restriction; if dietary control is insufficient, administration of an antihypertensive agent with 24-hour efficacy, which lowers vascular peripheral resistance, promotes sodium excretion, and potentially improves renal hemodynamics, is recommended. A calcium channel blocker may satisfy these requirements. PMID- 2220801 TI - Making history. PMID- 2220800 TI - Diet, smoking, and alcohol: influence on coronary heart disease risk. AB - The Framingham study on coronary heart disease (CHD) has shown that life-style, particularly diet, smoking, and alcohol consumption, has a great impact on the incidence of CHD. Blood lipoproteins, rather than total blood cholesterol, have been found to be more accurate predictors of CHD risk. Blood triglyceride, previously considered to have little bearing on CHD risk, was found to have a negative impact in many cases. A population subgroup with high triglyceride greater than or equal to 1.7 mmol/L (greater than or equal to 150 mg/dL), low high-density lipoprotein less than or equal to 1.04 mmol/L (less than or equal to 40 mg/dL), increased insulin resistance, and a higher incidence of diabetes mellitus has been found to be at increased risk for CHD. Diet intervention trials have shown that a reduction in total cholesterol and saturated fat consumption produced reduction in CHD incidence proportionate to the fall in cholesterol. Cigarette smoking increased CHD risk moderately; those who smoked one pack per day had twice the risk of nonsmokers. Alcohol consumption actually lowered CHD incidence in the Framingham study; however, when alcohol consumption was greater than two drinks per day, a rise in mortality from cancer and stroke was observed. PMID- 2220802 TI - Carrier screening for cystic fibrosis. PMID- 2220803 TI - Cystic fibrosis mutations in North American populations of French ancestry: analysis of Quebec French-Canadian and Louisiana Acadian families. AB - A 3-bp deletion (delta F508) in the cystic fibrosis (CF) gene is the mutation on the majority of CF chromosomes. We studied 112 CF families from North American populations of French ancestry: French-Canadian families referred from hospitals in three cities in Quebec and from the Saguenay-Lac St. Jean region of northeastern Quebec and Acadian families living in Louisiana. delta F508 was present on 71%, 55%, and 70% of the CF chromosomes from the major-urban Quebec, Saguenay-Lac St. Jean, and Louisiana Acadian families, respectively. A weighted estimate of the proportion of delta F508 in the French-Canadian patient population of Quebec was 70%. We found that 95% of the CF chromosomes with delta F508 had D7S23 haplotype B, the most frequent haplotype on CF chromosomes. In the Saguenay-Lac St. Jean families, 86% of the CF chromosomes without delta F508 had the B haplotype, compared with 31% for the major-urban Quebec and Louisiana Acadian families. The incidence of CF in the Saguenay-Lac St. Jean population was 1/895 live-born infants. PMID- 2220805 TI - Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin. AB - One hundred and two benign, mature ovarian teratomas and two immature, malignant teratomas were karyotyped and scored for centromeric heteromorphisms as part of an ongoing project to determine the chromosomal karyotype and the genetic origin of ovarian teratomas and to assess their utility for gene-centromere mapping. Karyotypic analysis of the benign cases revealed 95 46,XX teratomas and 7 chromosomally abnormal teratomas (47,XXX, 47,XX,+8 [two cases], 47,XX,+15, 48,XX,+7,+12 91,XXXX,-13 [mosaic], 47,XX,-15,+21,+mar). Our study reports on the first cases of tetraploidy and structural rearrangement in benign ovarian teratomas. The two immature cases had modal chromosome numbers of 78 and 49. Centromeric heteromorphisms that were heterozygous in the host were homozygous in 65.2% (n = 58) of the benign teratomas and heterozygous in the remaining 34.8% (n = 31). Chromosome 13 heteromorphisms were the most informative, with 72.7% heterozygosity in hosts. The cytogenetic data indicate that 65% of teratomas are derived from a single germ cell after meiosis I and failure of meiosis II (type II) or endoreduplication of a mature ovum (type III); 35% arise by failure of meiosis I (type I) or mitotic division of premeiotic germ cells (type IV). PMID- 2220804 TI - Deletions in patients with classical choroideremia vary in size from 45 kb to several megabases. AB - Making use of the p1bD5 probe (DXS165), we have isolated several markers from the choroideremia locus by chromosomal jumping, preparative field-inversion gel electrophoresis, and cloning of a deletion junction fragment. With these clones we were able to identify and characterize eight deletions in 69 choroideremia patients investigated. The deletions are heterogeneous, in both size and location. The smallest deletion (patient LGL1134) comprises approximately 45 kb of DNA, whereas the largest ones (patients 25.6 and LGL2905) span a DNA segment of at least 5 megabases, which is comparable in size to the smallest deletion detected in a TCD patient (patient XL45) showing a complex phenotype. The TCD deletions encompass variable parts of 150-200-kb DNA segment that is flanked by p1bD5 (DXS165) at the centromeric side and by pZ 11 at the telomeric side. The deletions in patients 33.1, LGL1101, and LGl1134 do not span a translocation breakpoint which was previously mapped on the X chromosome of a female with TCD. The clones isolated from the TCD locus are valuable diagnostic markers for deletion analysis of patients or carrier females. In addition, they should be useful for the isolation of expressed sequences that are part of the TCD gene. PMID- 2220807 TI - Phenotypic heterogeneity in osteogenesis imperfecta: the mildly affected mother of a proband with a lethal variant has the same mutation substituting cysteine for alpha 1-glycine 904 in a type I procollagen gene (COL1A1). AB - A proband with a lethal variant of osteogenesis imperfecta (OI) has been shown to have, in one allele in a gene for type I procollagen (COL1A1), a single base mutation that converted the codon for alpha 1-glycine 904 to a codon for cysteine. The mutation caused the synthesis of type I procollagen that was posttranslationally overmodified, secreted at a decreased rate, and had a decreased thermal stability. The results here demonstrate that the proband's mother had the same single base mutation as the proband. The mother had no fractures and no signs of OI except for short stature, slightly blue sclerae, and mild frontal bossing. As a child, however, she had the triangular facies frequently seen in many patients with OI. On repeated subculturing, the proband's fibroblasts grew more slowly than the mother's, but they continued to synthesize large amounts of the mutated procollagen in passages 7-14. In contrast, the mother's fibroblasts synthesized decreasing amounts of the mutated procollagen after passage 11. Also, the relative amount of the mutated allele in the mother's fibroblasts decreased with passage number. In addition, the ratio of the mutated allele to the normal allele in leukocyte DNA from the mother was half the value in fibroblast DNA from the proband. The simplest interpretation of the data is that the mother was mildly affected because she was a mosaic for the mutation that produced a lethal phenotype in one of her three children. PMID- 2220806 TI - Cytogenetic analysis of 750 spontaneous abortions with the direct-preparation method of chorionic villi and its implications for studying genetic causes of pregnancy wastage. AB - Altogether, 750 cases of spontaneous abortion between the fifth and 25th week of gestation were analyzed cytogenetically by the direct-preparation method using chorionic villi. The majority of cases (68%) were derived from early abortions before the 12th week of gestation. The frequency of abnormal karyotypes was 50.1%; trisomy was predominant (62.1%), followed by triploidy (12.4%), monosomy X (10.5%), tetraploidy (9.2%), and structural chromosome anomalies (4.7%). Among trisomies, chromosomes 16 (21.8%), 22 (17.9%), and 21 (10.0%) were prevalent. The frequency of chromosomally abnormal abortions increased with maternal age but only because of an increase of trisomy. Polyploidy and monosomy X, however, decreased. Mean maternal age was significantly increased for trisomies 16, 21, and 22 and was highest for trisomies 18 and 20. The results obtained are within the range of variability reported earlier from tissue culture-type studies. A consistent feature during our study is the excess of females in chromosomally normal abortions (male:female sex ratio 0.71). According to the methodology applied, maternal cell contamination and undetected 46,XX molar samples cannot have influenced the sex ratio. However, a bias introduced by social status or maternal age cannot be excluded. With the more rapid and convenient direct preparation of chorionic villi, reliable cytogenetic data on causes of spontaneous abortions can be obtained. PMID- 2220808 TI - Assignment of the Charcot-Marie-Tooth neuropathy type 1 (CMT 1a) gene to 17p11.2 p12. AB - Charcot-Marie-Tooth disease type 1a (CMT 1a) is an autosomal dominant peripheral neuropathy linked to the DNA markers D17S58 and D17S71, located in the pericentromeric region of the chromosome 17p arm. We analyzed an extended 5 generation Belgian family, multiply affected with CMT 1a, for linkage with eight chromosome 17 markers. The results indicated that the CMT 1a mutation is localized in the chromosomal region 17p11.2-p12 between the marker D17S71 and the gene for myosin heavy polypeptide 2 of adult skeletal muscle. PMID- 2220809 TI - Frequency of three Hex A mutant alleles among Jewish and non-Jewish carriers identified in a Tay-Sachs screening program. AB - Mutations in the HEX A gene, encoding the alpha-subunit of beta-hexosaminidase A (Hex A), are the cause of Tay-Sachs disease as well as of juvenile, chronic, and adult GM2 gangliosidoses. We have examined the distribution of three mutations--a 4-nucleotide insertion in exon 11, a G----C transversion at a 5' splice site in intron 12, and a 269Gly----Ser amino acid substitution in exon 7--among individuals enzymatically diagnosed as carriers of Hex A deficiency. Mutation analysis included polymerase chain reaction (PCR) amplification of the relevant regions of genomic DNA, followed by allele-specific oligonucleotide hybridization; another test for heterozygosity of the exon 11 insertion was based on the formation of heteroduplex PCR fragments of low electrophoretic mobility. The percentage distribution of the exon 11, intron 12, exon 7, and unidentified mutant alleles was 73:15:4:8 among 156 Jewish carriers of Hex A deficiency and 16:0:3:81 among 51 non-Jewish carriers. Regardless of the mutation, the ancestral origin of the Jewish carriers was primarily eastern and (somewhat less often) central Europe, whereas for the non-Jewish carriers it was western Europe. Because a twelfth of the Jewish carriers and four-fifths of the non-Jewish carriers of Hex A deficiency had mutant alleles other than the three common ones tested, enzyme-based tests cannot be replaced by DNA-based tests at the present time. However, DNA-based tests for two-carrier couples could identify those at risk for the chronic/adult GM2 gangliosidoses rather than for infantile Tay-Sachs disease. PMID- 2220812 TI - Screening for cystic fibrosis carriers. PMID- 2220813 TI - Some issues in the study of birth defects and recurrence risks in live births and "stillbirths". PMID- 2220811 TI - Definitive prenatal diagnosis for type III glycogen storage disease. AB - Prenatal diagnosis for type III glycogen storage disease was performed by using (1) immunoblot analysis with a polyclonal antibody prepared against purified porcine-muscle debranching enzyme and (2) a qualitative assay for debranching enzyme activity. Cultured amniotic fluid cells from three pregnancies (three families in which the proband had absence of debrancher protein) were subjected to immunoblot analysis. Two unaffected and one affected fetus were predicted. In addition, cultured amniotic fluid cells from nine pregnancies (eight families) were screened with a qualitative assay based on the persistence of a polysaccharide that has a structure approaching that of a phosphorylase limit dextrin when the cells were exposed to a glucose-free medium. This qualitative assay predicted six unaffected and three affected fetuses. All predictions by either method were confirmed postnatally except for one spontaneously aborted fetus. Our data indicate that a definitive diagnosis of type III glycogen storage disease can be made prenatally by these methods. PMID- 2220810 TI - DNA haplotype analyses of patients with hyperphenylalaninemia. AB - Linkage analysis of phenylketonurics has shown a strong association between the DNA haplotype at the phenylalanine hydroxylase (PAH) locus and phenylketonuria (PKU). Similarly, a genetic linkage between less severe forms of hyperphenylalaninemia (HPA) and the PAH locus has been suggested. In the present study we analyzed this linkage in more detail. Haplotypes at the PAH locus were determined for 19 individuals with moderately elevated plasma phenylalanine and normal urinary neopterin/biopterin ratios. Fourteen of these individuals had plasma phenylalanine levels of 4-10 mg/dl (mild HPA), and the other five had plasma phenylalanine levels of 10-19 mg/dl (atypical PKU). Thirteen of the 15 HPA families consisted of an affected child and at least one other sibling. Elevated plasma phenylalanine was seen to genetically segregate with specific PAH alleles in each family. Summation of the LOD scores for both categories of moderate plasma phenylalanine elevation gave a maximum value of 3.556 at theta = 0. At theta = 0 this gives a probability of linkage between the PAH locus and the locus for moderate phenylalanine elevations that is approximately 3,600:1. None of the alleles segregating with either mild HPA or atypical PKU were of haplotype 2 or 3, and 13/20 were of types 1 or 4. This is in agreement with the most deleterious mutations being on haplotypes 2 and 3 and with the less severe mutations being on haplotypes 1 and 4. chi 2 Analyses indicated no statistically significant correlation between HPA and a particular haplotype or restriction-enzyme site. PMID- 2220814 TI - Integrating genetics into the medical school curriculum. PMID- 2220815 TI - Physicians and other nongeneticists strongly favor teaching genetics to medical students in the United Kingdom. PMID- 2220816 TI - Innovations in human genetics education. Incorporation of genetics into a problem based medical school curriculum. AB - There has been recent interest in the development of problem-based human genetics curricula in U.S. medical schools. The College of Human Medicine at Michigan State University has had a problem-based curriculum since 1974. The vertical integration of genetics within the problem-based curriculum, called "Track II," has recently been revised. On first inspection, the curriculum appeared to lack a significant genetics component; however, on further analysis it was found that many genetics concepts were covered in the biochemistry, microbiology, pathology, and clinical science components. Both basic science concepts and clinical applications of genetics are covered in the curriculum by providing appropriate references for basic concepts and including inherited conditions within the differential diagnosis in the cases studied. Evaluations consist of a multiple choice content exam and a modified essay exam based on a clinical case, allowing evaluation of both basic concepts and problem-solving ability. This curriculum prepares students to use genetics in a clinical context in their future careers. PMID- 2220817 TI - Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. AB - To clarify its physiologic role, alkaline phosphatase (ALP) was examined in normal skin fibroblasts and was shown to be the tissue-nonspecific (TNS) isoenzyme type (as evidenced by heat and inhibition profiles) and to be active toward millimolar concentrations of the putative natural substrates phosphoethanolamine (PEA) and pyridoxal-5'-phosphate (PLP). Fibroblast ALP has a low-affinity activity, with a distinctly alkaline pH optimum (9.3), toward 4 methylumbelliferyl phosphate (4-MUP), PEA, and PLP but a more physiologic pH optimum (8.3) toward physiologic concentrations (micromolar) of PEA and PLP. Normal fibroblast ALP is linked to the outside of the plasma membrane, since in intact cell monolayers (1) dephosphorylation rates of the membrane-impermeable substrates PEA and PLP in the medium at physiologic pH were similar to those observed with disrupted cell monolayers, (2) brief exposure to acidic medium resulted in greater than 90% inactivation of the total ALP activity, and (3) digestion with phosphatidylinositol-specific phospholipase C (PI-PLC) released about 80% of the ALP activity. Hypophosphatasia fibroblasts were markedly deficient (2%-5% control values) in alkaline and physiologic ALP activity when 4 MUP, PLP, and PEA were used as substrate. The majority of the detectable ALP activity, however, appeared to be properly lipid anchored in ecto-orientation. Thus, our findings of genetic deficiency of PEA- and PLP-phosphatase activity in hypophosphatasia fibroblasts, as well as our biochemical findings, indicate that TNS-ALP acts physiologically as a lipid-anchored PEA and PLP ectophosphatase. PMID- 2220818 TI - Splicing defect at the ornithine aminotransferase (OAT) locus in gyrate atrophy. AB - Gyrate atrophy (GA), a recessive eye disease involving progressive vision loss due to chorioretinal degeneration, is associated with the deficiency of the mitochondrial enzyme ornithine aminotransferase (OAT), with consequent hyperornithinemia. We and others have reported a number of missense mutations at the OAT locus which result in GA. Here we report a GA patient of Danish/Swedish ancestry in whom one OAT allele produces an mRNA that is missing a single 96-bp exon relative to the normal mRNA. Polymerase-chain-reaction amplification and sequencing revealed a 9-bp deletion covering the splice acceptor region of exon 5, resulting in the absence of exon 5 sequences from the mRNA with no disruption to the reading frame. This mutation, which was not present in 15 other independent GA patients, adds to the array of allelic heterogeneity observed in GA and represents the first example of a splicing mutation associated with this disorder. PMID- 2220819 TI - Deletion mapping of Aland Island eye disease to Xp21 between DXS67 (B24) and Duchenne muscular dystrophy. AB - Aland Island Eye Disease (AIED) is an X-linked form of ocular hypopigmentation- also known as Forsius-Eriksson, or type 2, ocular albinism--in which affected males demonstrate subnormal visual acuity, protanomalous red-green colorblindness, axial myopia, astigmatism, hypoplasia of the fovea, and hypopigmentation of the fundus. A patient has previously been described who, in addition to AIED, manifested a contiguous gene syndrome which included congenital adrenal hypoplasia (AHC), glycerol kinase deficiency (GKD), and Duchenne muscular dystrophy (DMD). In the present paper report we report the molecular genetic analysis of his deletion. Initially, multiplex polymerase-chain-reaction amplification was used to screen for a DMD-locus deletion which was then further characterized, using DMD cDNA and genomic probes, via Southern blot analysis. The deletion includes the region encompassed by probes C7 (DXS28) and DMD cDNA 8. Probes B24 (DXS67) and DMD cDNA 5b-7 show normal hybridization patterns and appear to flank the deletion, while the DMD cDNA 8 detects a junction fragment. Molecular genetic techniques have mapped the deletion in this patient to the subbands Xp21.3-21.2, between DXS67 and DMD. PMID- 2220820 TI - Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3. AB - The lysosomal hydrolase alpha-L-iduronidase (IDUA) is one of the enzymes in the metabolic pathway responsible for the degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate. In humans a deficiency of IDUA leads to the accumulation of glycosaminoglycans, resulting in the lysosomal storage disorder mucopolysaccharidosis type I. A genomic subclone and a cDNA clone encoding human IDUA were used to localize IDUA to chromosome 4p16.3 by in situ hybridization and this was confirmed by Southern blot analysis. This localization is different from that of a previous report mapping IDUA to chromosome 22 and places the gene for IDUA in the same region of chromosome 4 as the Huntington disease gene. Measurement of expressed human IDUA activity in human-mouse hybrid cell lines confirmed that IDUA is on chromosome 4. PMID- 2220821 TI - More than one mutant allele causes infantile Tay-Sachs disease in French Canadians. AB - Two Tay-Sachs disease (TSD) patients of French-Canadian origin were shown by Myerowitz and Hogikyan to be homozygous for a 7.6-kb deletion mutation at the 5' end of the hexosaminidase A alpha-subunit gene. In order to determine whether all French-Canadian TSD patients were homozygotes for the deletion allele and to assess the geographic origins of TSD in this population, we ascertained 12 TSD families of French-Canadian origin and screened for occurrence of mutations associated with infantile TSD. DNA samples were obtained from 12 French-Canadian TSD families. Samples were analyzed using polymerase-chain-reaction (PCR) amplification followed by hybridization to allele-specific oligonucleotides (ASO) or by restriction analysis of PCR products. In some cases Southern analysis of genomic DNA was performed. Eighteen of the 22 independently segregating mutant chromosomes in this sample carried the 7.6-kb deletion mutation at the 5' end of the gene. One chromosome carried the 4-nucleotide insertion in exon 11 (a "Jewish" mutation). In this population no individuals were detected who had the substitution at the splice junction of exon 12 previously identified in Ashkenazi Jews. One chromosome carried an undescribed B1 mutation; this allele came from a parent of non-French-Canadian origin. Patients in three families carried TSD alleles different from any of the above mutations. The 5' deletion mutation clusters in persons originating in southeastern Quebec (Gaspe) and adjacent counties of northern New Brunswick. PMID- 2220823 TI - The pattern of factor IX germ-line mutation in Asians is similar to that of Caucasians. AB - To begin documenting the pattern of germ-line mutations in different human races, we have delineated the mutation in nine Korean families with hemophilia B by direct genomic sequencing of the regions of likely functional significance in the factor IX gene. An evaluation of these mutations in combination with previously described point mutations in the factor IX gene of Asians indicates that transitions predominate followed by transversions and microdeletions/insertions. Transitions at the dinucleotide CpG are a dramatic hot spot of mutation. This pattern of mutation is very similar to that observed in Caucasians with hemophilia B, despite the many differences between Asians (mostly Koreans) and Caucasians in diet, environment and cultural life-styles. The similarity may reflect the predominance of endogenous processes or ubiquitous mutagens rather than specific mutagens in the environment. The following additional conclusions emerge: (1) The missense mutations in Asians occur at evolutionarily conserved amino acids. When combined with the previous data this makes it likely that more than two-thirds of the missense mutations which could possibly occur at nonconserved amino acids do not cause hemophilia B. (2) Surprisingly, a change in the sixth base of the intron 2 donor splice-junction sequence is associated with severe disease in HB 74/77. (3) Direct carrier testing of nine Korean families demonstrates that the stability of DNA at ambient temperature in blood with the anticoagulant ACD solution B makes it feasible for a diagnostic laboratory to perform such testing at a distance of 7,000 miles. Carrier testing revealed that the mutation in HB78 arose in his mother's germ-line.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220824 TI - The probabilistic determination of identity-by-descent sharing for pairs of relatives from pedigrees. AB - Methods for detecting genetic linkage are more powerful when they fully use all of the data collected from pedigrees. We first discuss a method for obtaining the probability that a pedigree member has a given genotype, conditional on the phenotypes of his relatives. We then develop a rapid method to obtain the conditional probabilities of identity-by-descent sharing of marker alleles for all related pairs of individuals from extended pedigrees. The method assumes that the individuals are noninbred and that the relationship between genotype and phenotype is known for the marker locus studied. The probabilities of identity-by descent sharing among relative pairs, conditional on marker phenotype information, can then be used in any of the model free tests for linkage between a trait locus and a marker locus. PMID- 2220822 TI - Equal parental origin of chromosome 22 losses in human sporadic meningioma: no evidence for genomic imprinting. AB - Inactivation of tumor suppressor genes can occur either by mutation at the gene locus or by loss of part or all of the chromosome region containing the gene. The latter is most frequently detected by DNA markers as loss of heterozygosity in the tumor tissue. In several reports, the paternal homologue was preferentially retained in embryonal tumors associated with loss of particular chromosomal regions, suggesting genomic imprinting of the corresponding tumor suppressor loci. To explore the generality of these findings and the possible role of genomic imprinting in adult tumors of the nervous system, we have determined the parental origin of chromosome 22 loss in sporadic meningioma. Of nine cases studied, five tumors retained the maternally derived chromosome 22 homologue while four retained the paternally derived chromosome 22. Thus, in contrast to the embryonal tumors, the meningioma locus on chromosome 22 is inactivated by random mutation in sporadic adult meningiomas. PMID- 2220825 TI - Minisatellite allele diversification: the origin of rare alleles at the HRAS1 locus. AB - Three genetic markers within the promoter-exon 1 region of the HRAS1 locus have been employed to investigate lineage relationships among alleles of the highly polymorphic variable tandem repeat (VTR) immediately downstream of the HRAS1 gene. These markers were in absolute linkage disequilibrium with the HRAS1 VTR, allowing the assignment of unique upstream haplotypes to each of the four common VTR alleles. Analysis of 17 rare alleles revealed a stratification of allele fragment size and upstream haplotype in which each rare VTR allele possessed the markers characteristic of the common allele nearest in size. Therefore, hyperallelism emanated from the four common alleles in a defined fashion, the size of a rare allele specifying its origin. As discussed below, this result implies that unequal crossing-over between homologues is unlikely to be the predominant mechanism for generating new VTR alleles at this minisatellite locus. PMID- 2220826 TI - Further mapping of an ataxia-telangiectasia locus to the chromosome 11q23 region. AB - We recently mapped the gene for ataxia-telangiectasia group A (ATA) to chromosome 11q22-23 by linkage analysis, using the genetic markers THY1 and pYNB3.12 (D11S144). The most likely order was cent-AT-S144-THY1. The present paper describes further mapping of the AT locus by means of a panel of 10 markers that span approximately 60 cM in the 11q22-23 region centered around S144 and THY1. Location scores indicate that three contiguous subsegments within the [S144-THY1] segment, as well as three contiguous segments telomeric to THY1, are each unlikely to contain the AT locus, while the more centromeric [STMY-S144] segment is most likely to contain the AT locus. These data, together with recent refinements in the linkage and physical maps of 11q22-23, place the AT locus at 11q23. PMID- 2220828 TI - Preventing respiratory disease in swine confinement workers: intervention through applied epidemiology, education, and consultation. AB - A combined epidemiological and intervention study was conducted on 207 swine confinement farmers with matched comparison subjects. The objectives of the study were to define, in detail, the nature and disease determinants in this exposed group and to explore methods of disease prevention. This 5 year prospective study included three annual medical assessments of workers and complementary work environment assessments. Between the first and second assessment periods, an in depth educational intervention was conducted. An industrial hygiene consultation intervention was conducted between the second and third measurement periods. Outcome measurements included changes in knowledge, attitudes, and behavior following educational intervention. Additionally, the outcomes measured included changes in medical and environmental assessment over the 3 year assessment periods. Results of the baseline respiratory symptoms assessment are reported here. Nearly 20% of swine confinement workers reported chronic cough, and 25% reported phlegm (American Thoracic Society questionnaire). Both symptoms were significantly more prevalent in the confinement workers compared to a blue collar comparison group, but only phlegm production was more prevalent compared to nonconfinement farmers. Work-related symptoms were reported much more frequently than chronic symptoms (e.g., 87% of confinement workers reported work-related cough). Bronchitis as well as airways reactivity were all significantly more prevalent in confinement workers compared to nonconfinement workers. Smoking seemed to have an additive effect with confinement exposure. Bronchitis and chest tightness symptoms were reported to be more severe upon return to work after an absence of 7 days or more. Finally, 34% of workers reported episodes of organic dust toxic syndrome. PMID- 2220827 TI - Diversity of some gene frequencies in European and Asian populations. V. Steep multilocus clines. AB - Regions of abrupt genetic change, which result from either rapid spatial change of selective pressures or limited admixture, were investigated in Europe and Asia on the basis of eight red cell markers typed in 960 samples. Two methods were employed, one based on genetic distances and one on evaluation of the first derivative of the surfaces representing allele-frequency variation. Genetic divergence tends to be maximal between populations that are separated by physical factors (mountain ranges and seas) but also separated by cultural barriers (different language affiliation). This suggests that mating isolation, rather than adaptive response to environmental change, accounts for spatially abrupt genetic change at the loci studied and that cultural differences associated with language contribute to isolating populations. Although selection may have determined two wide allele-frequency gradients, the genetic structure of European and Asian populations seems primarily to reflect isolation by distance when investigated on a small scale and migration patterns (or absence of migration) when investigated on a larger scale. PMID- 2220829 TI - Cohort studies of immunologic lung disease among Wisconsin dairy farmers. AB - Traditionally, hypersensitivity pneumonitis (HP) or farmer's lung disease (FLD) was thought to be the major occupational respiratory problem of farmers. In recent years, other acute conditions, particularly organic dust toxic syndrome (ODTS), have been recognized as significant features of the agricultural respiratory disease picture. The differences between HP and ODTS are discussed in this article. A cohort of workers on 90 dairy farms has been under study since 1975. Prevalence of FLD was calculated at 4.2/1,000. Extensive immunologic testing of this group was conducted. Serum antibody reactivity to farmer's lung antigens was related to chronic symptoms of bronchitis and occupational asthma, but not FLD. Serology may be thought of as a measure of exposure, but not FLD. PMID- 2220830 TI - Work-related respiratory disorders among Finnish farmers. AB - Several research projects on work-related respiratory diseases have been conducted in Finland. One of the largest, "Farmers' Occupational Health Programme," was conducted by the Social Insurance Institution of Finland during 1973-1983 in cooperation with Kuopio Regional Institute of Occupational Health and the National Board of Health. The main objective of the program was to develop a model for occupational health services for farmers. As a part of the program, postal surveys were conducted in 1979 and 1982. The surveys allowed an analysis of both the prevalence and the mean annual incidence of asthma, farmer's lung, and chronic bronchitis as well as of background variables related to the diseases. More than every tenth farmer suffered from these respiratory diseases. The occurrence of chronic bronchitis (the most common disease) was, in general, related to farming types in which grain crops (including animal feeds) were handled. Chronic bronchitis was most prevalent among farmers who worked in piggeries, implying a combined effect of grain dusts, dusts of animal origin, and development of the disease. Atopy predisposed to and had an additive effect with smoking on chronic bronchitis. PMID- 2220831 TI - Practical aspects of sampling for organic dusts and microorganisms. AB - Air sampling for organic dusts and microorganisms was carried out in silos when moldy silage was discarded through the discharge chute. Concentrations of respirable dust and airborne viable microorganisms exceeded 20 mg/m3 and 1 x 10(9)/m3, respectively, when dry silage was removed from silos. Much lower concentrations of dust and microorganisms were present when wet silage was discarded. Impinger and filter cassette samplers were equally effective in collecting the hardy spores present in silage dusts. PMID- 2220832 TI - Presence of endotoxins in different agricultural environments. AB - Gram-negative bacterial endotoxins are contaminants of dusts from agricultural products. They represent a potential health hazard for farmers working in many different processes. However, the occurrence of endotoxins has not been well characterized in the various farming operations. Therefore, two farming activities with potential for generating airborne endotoxins were studied: 1) chopping of baled corn stalks or straw for bedding in New York State, and 2) oat bin unloading in Alabama. Actual airborne endotoxin levels in dusts obtained during bedding chopper operations far exceeded [90 endotoxin units (EU)/m3] the level at which acute pulmonary function decrements occur in cotton dust-exposed individuals. Endotoxin contamination of laboratory-generated dust from an oat sample likewise exceeded these levels. This study documents the presence of potentially hazardous exposures to endotoxins in two common farm processes, which expands the knowledge of airborne endotoxin exposures on the farm. PMID- 2220833 TI - Methodologic issues in exposure assessment for case-control studies of cancer and herbicides. AB - Epidemiologic studies of cancer and exposure to herbicides have shown puzzling inconsistencies. Exposure-response gradients have been reported for non-Hodgkin's lymphoma in Sweden and Kansas, but no significant associations were seen in New Zealand or Washington State. Subjects in these studies were categorized by exposure using information obtained primarily by interview. A number of questions can be raised regarding the reliability and validity of such an exposure assessment. We examined procedures used to assess pesticide exposures in case control studies of cancer to evaluate their limitations and their probable effects on risk estimates. Except for case recall bias, problems of misclassification in these studies would tend to bias risk estimates toward the null and dilute exposure-response gradients. These problems are, therefore, unlikely explanations for the positive associations between cancer and herbicide use noted in some investigations. A tendency for false-negative findings, however, is not reassuring, and improvements in exposure assessment are needed if epidemiologic investigations are to continue to provide reliable information on the relationships of cancer and pesticide exposure. PMID- 2220834 TI - Cancer in Iowa farmers: recent results. AB - Previous analysis of Iowa death certificates from 1971 through 1978 identified several cancers with significantly elevated mortality in farmers. Subsequent ecological studies identified farm practices, including pesticide usage, that might be associated with these mortalities. These results led to several case control studies and a similar analysis of more recent death certificates. 'Usual occupation' has been added to the death certificate tapes for the years 1979 1986. Cancer mortality in Iowa farmers for this period is very similar to that for 1971-1978. Case-control studies for acute lymphocytic leukemia and multiple myeloma indicated that farming in general is not a risk factor for either cancer type. However, exposure to general classes of insecticides and herbicides is associated with an elevated odds ratio in farmers for incidence of multiple myeloma. The odds ratios are not statistically significant at the 5% level, probably due to relatively small numbers of cases and controls exposed to any one class of pesticides. PMID- 2220836 TI - Pesticide illness surveillance: review of the National Pesticide Hazard Assessment Program. AB - Regarding consultations on pesticide exposures by Oregon State University, the following information is summarized: 1) source of queries; 2) locations of exposure; 3) types of chemicals; and 4) nature of the illnesses. The majority of queries involve nonagricultural exposures in the home and workplace. Principal sources of referral are from the National Pesticide Telecommunications Network (toll-free number), state departments of agriculture, and state extension services. In addition to illnesses, the system also responds to press releases such as those that occurred after the withdrawal of chlordane. Previously unsuspected clinical problems have been reported (suggesting new areas of research need), including cases associated with long-acting organophosphates, such as chlorpyrifos, and with the pyrethroids. PMID- 2220835 TI - Environmental epidemiology of non-Hodgkin's lymphoma in eastern Nebraska. AB - The incidence of non-Hodgkin's lymphoma (NHL) is increased in many counties in eastern Nebraska. Histologic analysis has revealed a twofold increase in the clinically aggressive, diffuse large cell subtype of NHL. To investigate the possible association between NHL and agricultural exposures, a population-based case-control study was conducted in eastern Nebraska in 1985. Telephone interviews were conducted with 201 men having histologically confirmed NHL and 725 controls. Among men, the use of the herbicide 2,4-D was associated with a 50% increased risk of NHL (OR 1.5, 95% CI 0.9, 2.4). Personal exposure to 2,4-D more than 20 days per year increased the risk threefold (OR 3.3, 95% CI 0.5, 22.1). Several classes of insecticides were also associated with increased risk: organophosphates (OR 1.9, 95% CI 1.1, 3.1), carbamates (OR 1.8, 95% CI 1.0, 3.2), and chlorinated hydrocarbons (OR 1.4, 95% CI 0.8, 2.3). As a result of intense agrichemical use, extensive contamination of shallow groundwater by nitrate and atrazine has also occurred in eastern Nebraska. A twofold increased incidence of NHL is present in counties with greater than 20% of the wells contaminated by nitrate (greater than 10 ppm) and in counties with intense fertilizer use. These findings suggest that NHL in eastern Nebraska may be related to the use of pesticides and nitrogen fertilizers. PMID- 2220837 TI - Effects of organophosphate insecticide residue variability on reentry intervals. AB - A stochastic simulation program was written to study the importance of residue variability in predicting excessive chronic (seasonal) cholinesterase (AChE) inhibition and acute illness among a cohort of agricultural harvesters grouped into crews exposed to AChE-inhibiting insecticides. It was concluded that residue variability can substantially affect the cohort's AChE level only for daily mean AChE inhibitions below 4% per day, increasing end-of-season mean AChE inhibition but actually decreasing the cohort's end-of-season variability. The incidence of acute individual and group (crew) AChE inhibitions in excess of that potentially producing clinical symptoms (assumed herein to be greater than 50% in a day), exhibits a fairly clear boundary as a function of a combination of the residue's mean and deviation. The predicted acute response accurately parallelled reported rates, thus validating the simulation model. PMID- 2220838 TI - Chronic neuropsychological sequelae of occupational exposure to organophosphate insecticides. AB - The early (immediate and delayed) neurotoxic effects of acute organophosphate intoxication are well documented in the scientific literature; lack of recognition and inappropriate treatment of occupational poisonings continue. Less well understood is the potential development of chronic neuropsychological sequelae from exposures to insecticides. We undertook two cohort studies to assess chronic neuropsychologic effects of insecticide poisoning. Based, in part, on our clinical evaluation of several patients, these studies included: 1) a retrospective cohort study assessing function at least 1 year following moderate to severe poisonings among farm workers; and 2) a prospective cohort study assessing neuropsychological function before and after a season of organophosphate exposures among pesticide applicators. A typical case description, the study design, methodologic problems, and preliminary findings of these ongoing studies are presented. PMID- 2220839 TI - Neurotoxic concerns of human pesticide exposures. AB - While the human effects of acute pesticide poisoning are well known, significant data gaps exist with regard to what is known about some of the chronic effects, particularly neurotoxic and behavioral aspects of organophosphate exposures. The extent of this concern is particularly high in Europe where these issues are being addressed by the World Health Organization and the United Nations Development Programme. These agencies are sponsoring a ten-nation, international study of chronic neurologic and neurotoxic sequelae. In the United States, evidence for chronic neurologic effects have come from case studies, clusters of neurologic disease, or from specific epidemiologic studies. For both toxicologic and epidemiologic reasons, it is essential that the neurobehavioral potential of low-level, prolonged exposure to pesticides and pesticide mixtures be more thoroughly investigated. Workers exposed to pesticides are one of the largest occupational populations at risk in the world. The effects of these occupational exposures on the worker's nervous system and behavior are just beginning to be investigated. PMID- 2220840 TI - Noise-induced hearing loss in randomly selected New York dairy farmers. AB - To understand better the effects of noise levels associated with dairy farming, we randomly selected 49 full-time dairy farmers from an established cohort. Medical and occupational histories were taken and standard audiometric testing was done. Forty-six males (94%) and three females (6%) with a mean age of 43.5 (+/- 13) years and an average of 29.4 (+/- 14) years in farming were tested. Pure Tone Average thresholds (PTA4) at 0.5, 1.0, 2.0, and 3.0 kHz plus High Frequency Average thresholds (HFA3) at 3.0, 4.0, and 6.0 kHz were calculated. Subjects with a loss of greater than or equal to 20 db in either ear were considered abnormal. Eighteen subjects (37%) had abnormal PTA4S and 32 (65%) abnormal HFA3S. The left ear was more severely affected in both groups (p less than or equal to .05, t test). Significant associations were found between hearing loss and years worked (odds ratio 4.1, r = .53) and age (odds ratio 4.1, r = .59). No association could be found between hearing loss and measles; mumps; previous ear infections; or use of power tools, guns, motorcycles, snowmobiles, or stereo headphones. Our data suggest that among farmers, substantial hearing loss occurs especially in the high-frequency ranges. Presbycusis is an important confounding variable. PMID- 2220841 TI - Hip joint arthrosis: an occupational disorder among farmers. AB - Observations among Swedish farmers indicate that coxarthrosis is a common disorder in farming populations. In this case-referent study, we describe relationships between farming and hip joint arthrosis. The case-group consisted of 105 persons who have had surgery because of coxarthrosis and the referents consisted of 222 randomly selected persons. Non-responders totaled 9%. Farming was significantly more common in the case group. The ratio varied between 2.1 and 3.2, varying with the length of time in farming. Longer exposure did not seem to result in greater risk. There was no risk elevation related to forestry or transportation work. Nor was there any over-representation of accidents with injuries to the lower extremities in the case group. Heavy work load did not seem to be related to the genesis of coxarthrosis. Farming is an amalgamation of different types of work. However, we develop the hypothesis from this study that tractor driving may be related to hip arthrosis. Unfavorable angles in the hip joints may occur during tractor driving. Other studies support this hypothesis, as it has been found that unsuitable conditions for the hip joints may be related to arthrosis. PMID- 2220843 TI - Doxorubicin multiple-dose vials. PMID- 2220842 TI - Aztreonam--vancomycin incompatibility. PMID- 2220845 TI - Managed-care pharmacy. PMID- 2220844 TI - Methylprednisolone for acute spinal cord injury. PMID- 2220846 TI - Revisiting "The strengths of pharmacy": the 1953 Remington Medal address. AB - Five reasons for the continued strength of the pharmacy profession, each of which was originally proposed in 1953 by Hugh Muldoon, are explored in this address by 1990 Remington Medalist Joseph A. Oddis. The strengths of pharmacy in the 1990s are based on the same factors that served the profession well in the 1950s. As outlined in Muldoon's 1953 Remington Medal address, these factors are (1) pharmacists' character and motivation, (2) the profession's public trust, (3) the profession's respect for education, (4) pharmacy's willingness to confront its problems, and (5) pharmacy's concern for the future. Today's pharmacists are strongly motivated; they continue to strive to raise the level of services provided in all practice settings and to maximize their value to patients. Pharmacists retain a high degree of public trust; they should take advantage of this position to expand their scope of services in areas such as managed care. During the 1990s pharmacy's concern for education is focused on pharmacy work force needs as a whole, including issues related to technical personnel and specialization as well as the role of the Pharm.D. degree in the overall education program. Pharmacy's willingness to resolve its problems is evident in the growth of such organizations as the Joint Commission of Pharmacy Practitioners, which has allowed the profession to achieve strength through unity. Pharmacy's concern for the future is reflected in the deliberations at recent conferences on Pharmacy in the 21st Century, where participants concurred that pharmacy's highest priority is to demonstrate and communicate to others its value in health care.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220847 TI - Understanding the resources and organization of an industry-based drug information service. PMID- 2220848 TI - Drug information services at Burroughs Wellcome Co. PMID- 2220849 TI - Drug information services at Genentech. PMID- 2220850 TI - Drug information services at Eli Lilly and Company. PMID- 2220851 TI - Drug information services at Pfizer labs. PMID- 2220852 TI - Drug information services at the Upjohn Company. PMID- 2220853 TI - Implementation of product-line management in a hospital pharmacy department. AB - The development and implementation of product-line management (PLM) in a pharmacy department is reviewed. The PLM system of hospital organization shifts the emphasis from function to product. The pharmacy department at a 737-bed nonprofit hospital adopted PLM in an effort to reach more directly the physician and patient markets, enhance the image of pharmacy, and help meet requirements of the Joint Commission on Accreditation of Healthcare Organizations. The department surveyed physicians and administrators to identify their product and service needs and surveyed pharmacy staff members to identify the perceived benefits and risks of a PLM system. A strategic-planning session was held to decide how best to match the pharmacy department's product lines with market needs. The team leaders were renamed clinical supervisors and were no longer responsible for defined physical areas but rather for clinical matters relating to patients in the product line assigned. Pharmacy's chosen product lines were oncology services, neuropsychiatry, maternal and child care, cardiovascular, operating room-anesthesia-pain clinic, and general medical. The transition is being accomplished one product line at a time; interested team leaders transfer into clinical supervisor positions by achieving clinical expertise within the relevant product lines. Despite some initial confusion, PLM contributed to job satisfaction and morale and allowed the pharmacy department to provide increased clinical consultation and intervention services. PLM enhanced the clinical pharmacy program and focused clinical services on the physician and ultimately the patient. PMID- 2220854 TI - Outcome-focused counseling program for quality assurance in ambulatory care. AB - An outcome-focused patient-counseling program designed to enhance quality assurance in ambulatory pharmaceutical care is described. Drugs for which counseling was mandatory because of their potential for association with an adverse outcome were listed. A checklist was created for each drug class to assist pharmacists in providing uniform information and to serve as a follow-up document for quality assurance. The completed forms are used to indicate which patients' charts should be pulled for review against quality assurance criteria for the monitored drug classes; the criteria function as indicators of an adverse outcome. Findings are summarized and presented at the monthly meeting of the departmental quality assurance committee. The program was phased in one drug class at a time. Between October 1988 and January 1989, 18 charts were reviewed for the two drug classes being monitored during that period. There were no patients to whom the indicators of an adverse outcome applied. The outpatient counseling program helped pharmacists to provide consistent information and to focus on those drugs with the highest potential for adverse outcomes. Incorporating the program into quality assurance activities made it easier to measure patient outcomes. PMID- 2220855 TI - Use of time clocks for employees in health-care institutions. AB - The reasons for time clock use in health-care institutions, the categories of workers required to use a time clock and other timekeeping methods, and the incidence of time-clock-related conflicts were studied. A questionnaire was mailed to a random sample of 565 hospitals in October 1989. Usable responses were received from 340 (60.0%) of the institutions. Reasons given for time clock use included payroll tabulation, overtime calculation, and ensuring fair payment. Thirty-four institutions (10.0%) required all employees to clock in, and 179 (52.6%) required some employees to do so. A written time card completed by the employee was the method used most frequently if a time clock was not used. Clinical pharmacists were required to clock in at 51 institutions (15.0%), staff pharmacists at 62 (18.2%), and pharmacy technicians at 144 (42.9%). Clinical nurse specialists and registered nurses clocked in at 88 (25.9%) and 169 (49.7%) hospitals, respectively, and licensed practical nurses and nurse's aides each clocked in at 176 hospitals (51.8%). Less than 6% of the hospitals required salaried pharmacists or nurses to use a time clock. Of the respondents, 152 (44.7%) reported that they were not aware of any conflicts or that no conflicts had been experienced. Inconvenience and inaccurate clocking were the most common sources of conflict cited. Most hospitals use time clocks for nonsalaried employees for bookkeeping purposes; dissatisfaction with this method of tracking hours worked does not appear to be widespread. PMID- 2220856 TI - Using pharmacists' perceptions in planning changes in pharmacy practice. AB - Pharmacists' perceptions of and goals for clinical pharmacy services, as well as the proportion of time devoted to clinical services, were studied at one hospital as part of the process for establishing departmental goals. Three methods were used in evaluating pharmacists' perceptions of clinical pharmacy services. The first was a departmental survey. Second, staff members were asked to generate and prioritize a list of goals for clinical pharmacy services; this was done by means of an interactive, small-group process. Finally, a work-sampling study was performed that indirectly measured use of staff pharmacist and technician time. Staff pharmacists perceived that clinical pharmacy services were being provided to individual patients; however, support for these services from upper management was perceived as inadequate. Staff development had the highest priority for the further development of clinical pharmacy services. Only 19.7% of pharmacists' time was devoted to clinical services. Data from all three studies were incorporated into the development of a strategic plan that set forth long-term departmental goals and objectives. The plan includes a statement of commitment to develop management systems to eliminate deficiencies identified in the study. Among the changes in pharmacy operations introduced as a result of the survey were (1) a career-ladder system, (2) new opportunities for staff development, and (3) improved documentation systems. Surveying staff perceptions of existing services, joint goal setting and prioritization, and work-sampling studies formed the basis for the development and implementation of a new model of integrated pharmacy services at this institution. PMID- 2220857 TI - Promotion of extended-release niacin tablets at a Veterans Affairs medical center. AB - A program to modify the prescribing of antilipemic agents by promoting the use of extended-release niacin tablets is described. Between December 1987 and August 1988, pharmacists at a 1188-bed Veterans Affairs medical center observed a large increase in the number of outpatient prescriptions for antilipemic agents. In an attempt to control costs, a program to promote the use of extended-release niacin tablets for treating hyperlipemia was conducted during August and September 1988. Various educational materials on niacin were distributed to physicians. A display on therapy of hyperlipemia was featured at the monthly drug fair, and articles on niacin were presented during a journal club meeting of ambulatory-care clinicians. Pharmacists succeeded in having extended-release niacin tablets placed on the formulary in September. Data on the number of prescriptions filled for antilipemic agents were collected before and after the niacin promotional program. The number of prescriptions filled for extended-release niacin 500-mg tablets increased steadily during a six-month study period after the program ended; the number of prescriptions filled for regular niacin decreased by 50%. As prescribing of extended-release niacin increased, prescribing of colestipol, gemfibrozil, and probucol declined. The promotional program was well received by most of the medical staff. A program of education and formulary management successfully changed physician prescribing habits for antilipemic agents. PMID- 2220858 TI - Stability of fentanyl citrate and bupivacaine hydrochloride in portable pump reservoirs. AB - The stability of fentanyl citrate and bupivacaine hydrochloride in an admixture with 0.9% sodium chloride injection in portable pump reservoirs with or without overwraps was investigated. Twelve 100-mL samples containing fentanyl 20 micrograms/mL and bupivacaine hydrochloride 1250 micrograms/mL were placed in the plastic drug reservoirs, and 1-mL quantities were withdrawn immediately after preparation and at intervals during 30 days of storage. Six reservoirs were refrigerated (3 degrees C) and six stored at room temperature (23 degrees C); three at each temperature were placed in overwraps. All samples were observed for precipitation and for change in color or pH and were analyzed for drug concentration by high-performance liquid chromatography. No precipitation or change in color or pH was observed during the 30-day storage period. No loss of fentanyl or bupivacaine was detected in either the wrapped or the unwrapped samples. Fentanyl citrate and bupivacaine hydrochloride in 0.9% sodium chloride injection appear to be compatible, and admixtures containing the two drugs at the concentrations studied can be stored without overwraps for up to 30 days at refrigerated or room temperature without any significant loss of potency. PMID- 2220859 TI - Stability of morphine sulfate in Cormed III (Kalex) intravenous bags. AB - The stability of various concentrations of morphine sulfate solution stored in Cormed III (Kalex) i.v. bags at two temperatures was investigated. Solutions of morphine sulfate 0.5, 15, 30, and 60 mg/mL were prepared under a horizontal laminar-airflow hood with 0.9% sodium chloride solution and placed into 100-mL Kalex bags. Two bags were prepared for each concentration; one was stored at 5 degrees C and the other at 37 degrees C. Samples were analyzed in triplicate by high-performance liquid chromatography on days 0, 2, 5, 9, and 14. All morphine sulfate solutions were stable for 14 days at 37 degrees C, and the 0.5-, 15-, and 30-mg/mL solutions were stable for 14 days at 5 degrees C. However, the 60-mg/mL solution stored at 5 degrees C was found to contain 57% of the actual initial concentration on day 9 and 51% on day 14; the decrease coincided with the appearance of a white precipitate. Beginning on day 5, all the solutions displayed a light brown color that darkened as the study proceeded. This qualitative change was not associated with any change in morphine concentration. Solutions of morphine sulfate 0.5 to 60 mg/mL stored at 5 or 37 degrees C were stable for 14 days in Kalex bags, except for 60-mg/mL solutions stored at 5 degrees C for nine days or longer. PMID- 2220860 TI - Stability of ranitidine in intravenous admixtures stored frozen, refrigerated, and at room temperature. AB - The stability of ranitidine in concentrations of 0.5, 1.0, and 2.0 mg/mL in admixtures with commonly used i.v. fluids was studied. The admixture vehicles were 0.9% sodium chloride, 5% dextrose, 10% dextrose, 5% dextrose and 0.45% sodium chloride, and 5% dextrose with lactated Ringer's (DLR) injections in polyvinyl chloride bags. Three bags were prepared for each test solution and stored under each of the following conditions: seven days at room temperature (23 +/- 1 degrees C) in normal laboratory lighting, 30 days at 4 degrees C, and 60 days at -20 degrees C followed by either seven days at room temperature (in light) or 14 days at 4 degrees C. Ranitidine content was determined by high performance liquid chromatography at several intervals. Color, clarity, and pH were also examined. Ranitidine concentrations remained greater than or equal to 90% of initial concentrations under all storage conditions except in the frozen DLR admixtures. Drug loss in the DLR admixtures was greatest at the lower ranitidine concentrations. The only visual changes were yellow color in the thawed DLR admixtures and those containing ranitidine 2.0 mg/mL in 5% dextrose and 0.45% sodium chloride. Slight increases in the pH of some admixtures were noted. Ranitidine is stable for seven days at room temperature and 30 days at 4 degrees C at all concentrations and in all vehicles studied. At the studied concentrations, the drug is stable in admixtures frozen for 60 days and stored for seven days at room temperature or 14 days refrigerated, except in DLR admixtures; these admixtures should not be stored frozen. PMID- 2220861 TI - Managed care: the second generation. AB - The current status of managed health care is described and its impact on hospital and pharmacy operations is summarized. In the 1980s, managed care evolved into a three-segment industry, comprising health maintenance organizations (HMOs), preferred-provider organizations, and fee-for-service plans. Five new trends are emerging as managed care, now an established part of the country's health-care delivery system, enters its second generation: dual- and triple-option plans with financial risk sharing between employers and insurers/HMOs, point-of-service determination of benefits and coverage, consolidation of the number of options offered by employee health plans, creation of exclusive provider organizations, and direct provider contracting. Persons charged with negotiating managed-care contracts will make use of three primary cost-management methods: benefit design, provider reimbursement, and prospective pricing. Employees will take an increasingly active part in purchase decisions. Enrollees will face tradeoffs between their desire for maximum freedom of choice of provider and higher premiums, deductibles, and out-of-pocket expenses. Managed-care plans will continue to have a strong impact on hospitals, especially in the areas of reimbursement and use review. The effect of managed care on pharmacy operations will vary from institution to institution; among the positive results may be increased appreciation of the role of clinical pharmacy services in reducing the incidence of readmissions and the length of hospital stays. The result of these changes in the structure of health-care benefits will be greater price sensitivity, marked by a suppression of unnecessary use of health-care services and an increased tendency to compare and evaluate health-plan costs. PMID- 2220862 TI - Employer management of employee health plans. AB - Current trends in employer management of health-care plans are summarized, and the role of managed care is emphasized. Employers realize that employees perceive health-care plans as an important benefit and that attractive benefit plans will help in recruiting and retaining employees. At the same time, companies are faced with the need to find new ways in which to curtail the rising cost of health benefit plans, which often constitute their largest and most uncontrollable budget item. Such techniques as more effective claims administration, plan design changes, plan financing arrangements, education of employees, and increased employee cost sharing are among the cost-containment actions that employers are implementing. Managed-care networks including health maintenance organizations are often viewed as the ultimate cost-containment model; however, the effectiveness of these evolving arrangements must be rigorously evaluated on the basis of appropriate performance criteria and documentation of achievement. Faced with cost-containment pressures, employers are taking a more assertive and informed role in health-plan purchasing decisions. The future course of health care delivery will depend in large part on the response of corporate management to the challenge of ensuring that their employees receive quality health care at controllable costs. PMID- 2220863 TI - Shared-risk arrangement between employers and insurers. AB - Development of and initial experience with a shared-risk arrangement between an employer, Allied-Signal, Incorporated, and a health insurer, CIGNA Corporation, are discussed. Rapidly rising health-plan costs and projections for even greater increases in the next three years, coupled with other related considerations, spurred Allied-Signal to undertake a major re-evaluation of its employee health plan in 1987. After extensive discussions and consultation, Allied-Signal negotiated a shared-risk contract with CIGNA, a dual-option insurer, under which premium price increases are capped for a period of three years. CIGNA is at risk for any costs that exceed premium revenue; if costs are less than premium revenue, CIGNA will retain the surplus. Price and geographic accessibility to Allied-Signal beneficiaries were the two key factors in the choice of CIGNA Corporation. The company selected a point-of-service delivery model, which grants employees greater freedom of choice in the use of health-care providers; those who use network providers pay a fixed copayment while those who use nonnetwork providers pay a fixed copayment providers pay an annual deductible plus 20% of medical expenses incurred above the deductible. During the first year of the program, 75% of beneficiaries used network providers from 95% to 100% of the time. The actual costs for the first 18 months were less than projected and much less than increases experienced by fee-for-service plans during that same period. The shared-risk contract between Allied-Signal and CIGNA Corporation has been successful thus far.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2220864 TI - Screening discharge prescriptions on a pediatric ward. PMID- 2220865 TI - Trends in advertisements as an indicator of pharmacy work-force demand. PMID- 2220866 TI - Survey of technician use in hospital and community pharmacies in South Carolina. PMID- 2220867 TI - Reducing costs by adjusting dosage intervals for intravenous ranitidine. PMID- 2220868 TI - Impact of computerization on New England hospital pharmacy personnel. PMID- 2220869 TI - Use of premixed frozen small-volume injections in a small community hospital. PMID- 2220870 TI - Stability of famotidine frozen in polypropylene syringes. PMID- 2220872 TI - The pharmacist as an expert witness. PMID- 2220871 TI - Pharmacist's qualifications as an expert witness on a physician's standard of care. PMID- 2220873 TI - Cyclophosphamide: to pulse or not to pulse? PMID- 2220874 TI - Treatment of Wegener's granulomatosis with intermittent high-dose intravenous cyclophosphamide. AB - PURPOSE: Concerns regarding the long-term toxicity of daily cyclophosphamide (CP) therapy for the systemic vasculitides have led us to evaluate alternative approaches to treatment in an attempt to achieve comparable efficacy with less toxicity. This study sought to determine the efficacy, toxicity, and immunologic effects of glucocorticoids (GC) and intermittent high-dose intravenous CP ("pulse" CP) in the treatment of 14 patients with Wegener's granulomatosis (WG). PATIENTS AND METHODS: The diagnosis of active WG was supported by a typical clinical presentation and histopathologic findings of vasculitis, granulomatous inflammation, and tissue necrosis. GC treatment was initially provided on a daily basis and later tapered to an alternate-day schedule if vasculitis remained inactive. Pulse CP treatment was initially administered once a month for 6 months. If after 6 months remission had been attained and GC therapy had been discontinued, then pulse CP treatment was given at less frequent intervals thereafter. Treatment and evaluation were provided for participants as inpatients in a clinical research center (National Institutes of Health). RESULTS: Thirteen of 14 patients (93%) initially experienced unequivocal improvement with pulse CP therapy, and seven of 14 (50%) achieved remission within 4 months. However, treatment was associated with significant toxicity in two patients and later relapses in nine patients, so that a total of 79% either failed to achieve sustained remission or were unable to continue therapy. Three of 14 (21%) patients have achieved sustained remissions with the pulse CP protocol and one additional patient (who had a limited exacerbation of WG) continues to receive that therapy after 14 to 22 months (mean 17 months). CONCLUSIONS: The use of pulse CP and GC therapy in 14 patients with WG was associated with a high initial response rate. However, failure to respond initially to treatment, to sustain improvement, or to tolerate continued treatment was noted in 79% of patients within a period of 1 to 22 months. These observations indicate that this particular pulse CP protocol does not achieve a high degree of lasting efficacy. PMID- 2220875 TI - Digitalis-like activity in human plasma: relation to blood pressure and sodium balance. AB - PURPOSE: On the assumption that renal tubular cells are more important as the target cells for a natriuretic factor than blood cells, we used a well characterized cultured renal tubular cell line, Madin-Darby canine kidney (MDCK), cells to monitor the circulating digitalis-like factor in human plasma and examine its role in the regulation of blood pressure and sodium balance. SUBJECTS AND METHODS: We investigated the effects of plasma on binding of radioactive ouabain to monolayered MDCK cells in order to determine the level of a circulating digitalis-like factor. First, we measured specific 3H-ouabain binding to MDCK cells in the presence of plasma from 71 outpatients (34 normotensive subjects and 37 hypertensive patients) after incubation for 4 hours. Second, we measured specific 3H-ouabain binding after incubation of cells with plasma from 16 hospitalized subjects (eight normotensive subjects and eight hypertensive patients) receiving low and high sodium diets. RESULTS: In Study 1, ouabain binding was lower by 30% with plasma from hypertensive patients than with plasma from normotensive subjects (p less than 0.01). There was a significant negative correlation between individual subject's systolic or mean blood pressure and ouabain binding (r = -0.34, p less than 0.01 or r = -0.29, p less than 0.01). In Study 2, ouabain binding was also significantly reduced by 25% in the presence of plasma from hypertensive subjects as compared with plasma from normotensive subjects irrespective of sodium intake (p less than 0.01). A significant negative correlation was also found for all subjects between either systolic, diastolic, or mean blood pressure and ouabain binding (r = -0.58, p less than 0.01, r = 0.51, p less than 0.01, or r = -0.55, p less than 0.01, respectively). With the changes from low to high sodium intake, there was a corresponding decrease in ouabain binding (p less than 0.01) and an increase in sodium excretion (p less than 0.01). A significant negative correlation was observed between these two parameters (r = -0.47, p less than 0.05). CONCLUSIONS: These findings suggest that a circulating digitalis-like factor, which may act on renal tubular cells as the ouabain-displacing compound, is increased in patients with essential hypertension and also demonstrate that plasma levels may be influenced by changes in dietary sodium intake. PMID- 2220876 TI - Effect of dietary protein restriction on functional renal reserve in diabetic nephropathy. AB - PURPOSE, PATIENTS, AND METHODS: Functional renal reserve in patients with insulin dependent diabetes mellitus, as determined by the glomerular filtration rate (GFR) response test, is a measure of the capacity of the kidney to increase glomerular filtration in response to the stimulus of a protein meal or amino acid infusion. This 12-month study evaluated the changes in functional renal reserve in eight patients with insulin-dependent diabetes mellitus with nephropathy (micro-albuminuria [greater than or equal to 30 micrograms/minute]) who chronically decreased their dietary protein intake to a mean of 0.6 g/kg/day (Group 1) compared with a group of similar patients (n = 7) who maintained their unusual dietary protein intake (1.0 g/kg/day, Group 2). Patients were evaluated and measurements taken at 3-, 6-, and 12-month intervals. Absolute and percent increases in GFR were calculated from three averaged 1-hour measurements after an 80-g protein test meal. RESULTS: Although the initial absolute mean rise (14 +/- 12 versus 18 +/- 13 mL/minute/1.73 m2) in GFR and maximal percent rise (16% +/- 16% versus 32% +/- 27%) after the meal did not differ significantly between the two groups, at 12 months, values in the lower protein group increased (27.8 +/- 9.5 mL/minute/1.73 m2 and 54.7% +/- 48.8%), whereas those in the normal protein intake group declined significantly (3.7 +/- 3.6 mL/min-ute/1.73 m2 and 6.5% +/- 6.5%) (p less than 0.05). Both urine urea and microalbuminuria decreased significantly (p less than 0.05) in the low protein group. Unstimulated GFR at the end of 12 months was significantly less (p less than 0.05) in Group 2 (47 +/- 2 mL/minute/1.73 m2) than in Group 1 (71 +/- 21 mL/minute/1.73 m2). The rate of decline in GFR was significantly greater (p less than 0.05) in the normal protein intake group than in the low protein intake group (0.68 +/- 0.4 versus 0.28 +/- 0.15 mL/minute/1.73 m2/month). CONCLUSIONS: This study indicates that sustained dietary protein restriction can help to preserve renal function, decrease albuminuria, and lower the baseline GFR while maintaining functional renal reserve in patients with insulin-dependent diabetes mellitus. PMID- 2220877 TI - Treatment of the anemia of chronic renal failure with subcutaneous recombinant human erythropoietin. AB - PURPOSE: The purpose of this study was to determine the efficacy of recombinant human erythropoietin (rHuEPO) given subcutaneously three times/week in patients with chronic renal failure and anemia (predialysis). PATIENTS AND METHODS: Eleven patients with predialysis chronic renal failure participated in a double-blind, placebo-controlled study of subcutaneously administered erythropoietin. For 12 weeks, patients received either rHuEPO 100 mu/kg body weight three times/week subcutananeously or a placebo. After 12 weeks of placebo, patients now also received rHuEPO in a dose up to 150 mu/kg three times/week until target hematocrit was achieved. Throughout the study, blood pressure was monitored closely and blood work was obtained regularly for hemoglobin, hematocrit, reticulocyte count, and iron profile determinations. RESULTS: At 12 weeks, the hematocrit of the treated group had risen from 29% +/- 2% to 35% +/- 2% (p less than 0.001). The placebo group baseline hematocrit was 28% +/- 2% and at 12 weeks 26% +/- 2% After 12 weeks of rHuEPO therapy, the hematocrit of the prior placebo group was 32% +/- 2% (p less than 0.001 versus baseline). No significant change in biochemical parameters was noted. Mean blood pressure values were comparable before and after treatment. All protein ultimately required iron supplementation. In two patients, the rate of progression of renal failure appeared to increase as their hematocrit rose and rHuEPO was discontinued. CONCLUSIONS: It is concluded that rHuEPO given subcutaneously is an effective and safe therapy for patients with chronic renal failure who are anemic and who are not receiving dialysis. PMID- 2220878 TI - Pleuritis as a manifestation of reactivation tuberculosis. AB - PURPOSE: The purpose of this study was to determine the frequency with which tuberculous pleuritis is a manifestation of reactivation tuberculosis and to compare the clinical manifestations of reactivation tuberculous pleuritis with "classic" tuberculous pleuritis, in which chest roentgenograms reveal no parenchymal infiltrates. PATIENTS AND METHODS: We evaluated the medical records of 59 patients in whom tuberculous pleuritis was confirmed by histologic findings or mycobacterial culture. Twenty-seven patients (46%) had typical chest roentgenographic findings of reactivation tuberculosis, whereas 32 (54%) had classic tuberculous pleuritis. The clinical and laboratory features of these two groups were compared. RESULTS: Symptoms were more prolonged and pleural fluid glucose and lactate dehydrogenase concentrations were more markedly abnormal in patients with reactivation pleuritis than in those with classic pleuritis, suggesting a more chronic inflammatory process in the former group. Compared with patients with classic tuberculous pleuritis, those with reactivation pleuritis had a lower frequency of reactive tuberculin skin tests (61% versus 88%) and granulomatous pleural inflammation (25% versus 72%), but a higher bacillary burden, manifest by a higher frequency of positive sputum smears for acid-fast bacilli (50% versus 0%) and positive mycobacterial cultures from sputum (60% versus 23%) and pleural fluid (91% versus 66%). CONCLUSIONS: In contrast to previous reports, tuberculous pleuritis was a manifestation of reactivation tuberculosis in 46% (27 of 59) of patients. Tuberculous pleuritis is a more chronic process in patients with reactivation disease than in those with classic pleuritis. The lower frequency of reactive tuberculin skin tests and granuloma formation, combined with the higher bacillary burden in patients with reactivation pleuritis, suggest that these patients mount a less effective immune response to Mycobacterium tuberculosis infection than do patients with the classic form of tuberculous pleuritis. PMID- 2220879 TI - Association of Helicobacter pylori infection with dyspeptic symptoms in patients undergoing gastroduodenoscopy. AB - PURPOSE: To determine the prevalence of Helicobacter pylori in patients with non ulcer dyspepsia and ulcer disease as well as in a control population undergoing endoscopic retrograde cholangiopancreatography (ERCP) for suspected pancreatic or biliary disease. PATIENTS AND METHODS: Forty-six eligible patients undergoing upper endoscopy at Massachusetts General Hospital were studied over a period of 18 months, as well as 24 patients undergoing ERCP for presumed pancreatic or biliary disease. Two biopsy specimens from the fundus and two from the antrum were taken for microbiologic and histopathologic analysis. Sera were examined by enzyme-linked immunoabsorbent assay. All specimens were processed in a blind fashion. Chi-square test with Yates' correction was used for statistical analysis. RESULTS: H. pylori was found in 31 of 46 (67%) study patients and in six of 24 (25%) control patients (by microbiologic or histologic techniques) (p less than 0.01). H. pylori was found in all patients with peptic ulcer disease and in 60% of patients without ulcers. No association between H. pylori and any specific gastrointestinal symptom was observed. H. pylori was identified in the fundus as often as in the antrum, although in the antrum the organism was more often associated with histologic gastritis. Compared with histology, serologic assays for IgG and IgA antibodies to H. pylori had sensitivities of 100% and 94%, and specificities of 86% and 76%, respectively. Reexamination of selected specimens without knowledge of their identity revealed that the specificity of serology exceeded 94% while the sensitivity of histologic and microbiologic studies may have been closer to 80%. CONCLUSIONS: H. pylori was more common in dyspeptic patients than in our control subjects undergoing ERCP. Multiple biopsy sites from fundus and antrum are required to exclude infection. Serologies of IgG and IgA were sensitive and specific for H. pylori, suggesting a possible role for non-endoscopic diagnosis of this infection. The frequent association of H. pylori with active inflammation rather than with quiescent gastritis is consistent with a pathologic role of this organism. PMID- 2220880 TI - Evidence of subclinical blastomycosis in forestry workers in northern Minnesota and northern Wisconsin. AB - PURPOSE: To investigate the incidence of remote subclinical blastomycosis in a high-risk population of forestry workers. PATIENTS AND METHODS: The study consisted of 39 male forestry workers from northern Minnesota and northern Wisconsin, areas endemic for blastomycosis but not for histoplasmosis. All subjects were histoplasmin skin test-negative, and none had ever been diagnosed with blastomycosis or pneumonia. An antigen-specific lymphocyte stimulation assay was performed to determine the presence of blastomycosis. RESULTS: Peripheral blood lymphocytes from 12 of 39 subjects demonstrated specific antigen-induced proliferation when stimulated with a purified alkali- and water-soluble antigen derived from the cell wall of Blastomyces dermatitidis. CONCLUSION: The finding that 30% of these men had evidence of previous blastomycosis suggests that subclinical cases do occur sporadically, and are probably more common than diagnosed symptomatic cases. This is similar to histoplasmosis, in which the majority of infections are subclinical. However, the reservoir of persons with previous undiagnosed blastomycosis is probably small compared to the huge number of persons (perhaps 30 million) with prior histoplasmosis. PMID- 2220881 TI - Cardiorespiratory effects of endoscopic esophageal variceal sclerotherapy. AB - Endoscopic variceal sclerotherapy (EVS) is an effective means of controlling variceal hemorrhage, which develops as a consequence of portal hypertension. While esophageal perforation, ulceration, strictures, and mediastinitis are potential complications associated with this procedure, it is not clear whether isolated pleuropulmonary events such as pleuritis, pneumonitis, and adult respiratory distress syndrome are causally related to the EVS. Endoscopy and sedation with the attendant risk of aspiration, particularly in the background of hepatic encephalopathy, may account for some of these events. Recent controlled studies of respiratory function demonstrate that EVS as such results in minor changes in gas exchange, lung volumes, and pulmonary and systemic hemodynamics. Most pulmonary complications have been reported with the use of sodium morrhuate sclerosant. Comparative studies among different sclerosants are necessary to evaluate relative safety. Finally, there have been rare reports of myocardial ischemia and pericarditis reported in association with EVS, but these are of a transient nature. Chest symptoms, roentgenographic pleuropulmonary changes, pulmonary hemodynamics, and cardiac perturbations are transient and should not preclude offering EVS to patients with variceal hemorrhage. PMID- 2220882 TI - Refractory ventricular arrhythmias and death in a 43-year-old man. PMID- 2220883 TI - Supersensitivity of isolated coronary artery to ergonovine in a patient with variant angina. PMID- 2220884 TI - Congenital methemoglobinemia due to methemoglobin reductase deficiency in two unrelated American black families. PMID- 2220885 TI - Disappearance of muscular calcium deposits during resolution of prolonged rhabdomyolysis-induced hypercalcemia. PMID- 2220886 TI - Acute eosinophilic colitis and hypersensitivity reaction associated with naproxen therapy. PMID- 2220888 TI - Extraneural manifestations of chronic inflammatory demyelinating polyradiculoneuropathy. PMID- 2220887 TI - Successful treatment of gastroparesis with erythromycin in a patient with progressive systemic sclerosis. PMID- 2220891 TI - Primary intracranial meningeal lymphoma. PMID- 2220890 TI - Massive rhabdomyolysis: a rare presentation of primary Vibrio vulnificus septicemia. PMID- 2220889 TI - Lepromatous leprosy and seropositivity for HTLV-I. PMID- 2220892 TI - Stroke in protein C deficiency. PMID- 2220893 TI - Resolution of prosthetic valve stenosis (presumed thrombosis) without thrombolytic therapy or surgical intervention. PMID- 2220894 TI - Trends in the scientific literature on cocaine. PMID- 2220895 TI - Asymptomatic carrier state for cryptosporidium. PMID- 2220896 TI - Pancreatitis and typhoid fever. PMID- 2220897 TI - Pyrrolizidine poisoning. PMID- 2220899 TI - A CPT code for "caring". PMID- 2220898 TI - Autoantibodies to vascular endothelial cell antigens in systemic vasculitis. PMID- 2220900 TI - Midwest jobfocus. The best of all worlds. PMID- 2220902 TI - Chicago jobfocus. Magnetic milieu. PMID- 2220901 TI - Self-confidence: a feeling you can create. PMID- 2220903 TI - Ninety years through nursing's lens. PMID- 2220904 TI - National study on nurses' and physicians' attitudes on AIDS. PMID- 2220905 TI - Resurrection drug. PMID- 2220906 TI - Helping patients recover faster. PMID- 2220907 TI - Critical care. From sentinels to specialists. PMID- 2220908 TI - Pain management. Nurses lead the way to new priorities. PMID- 2220910 TI - Military nurses rally for Operation Desert Shield. PMID- 2220909 TI - Wound care. Trial & error yields to knowledge. PMID- 2220911 TI - Professional status. The struggle for just compensation. PMID- 2220912 TI - Drug therapy. The history of a life affair. PMID- 2220913 TI - The first seventy years. PMID- 2220914 TI - Contraception and ectopic pregnancy risk. AB - Studies of the association of ectopic pregnancy with contraception have generated a conflicting array of results because of methodologic differences between studies. We estimated the absolute incidence rates of ectopic pregnancy for various contraceptives by multiplying the pregnancy rate by the proportion of pregnancies with ectopic implantation for each method. Our results indicated a more than 500-fold difference in ectopic pregnancy incidence, from a low of 0.005 ectopic pregnancies per 1000 women years of oral contraception or vasectomy to a high of 2.6 per 1000 women years of no contraception. These estimated incidence rates should be useful for clinicians and patients seeking to better understand the risks and benefits of contraceptives. PMID- 2220915 TI - Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations. AB - Results are presented of a randomized, double-blinded controlled clinical trial of calcium supplementation (2.0 gm of elemental calcium as calcium carbonate) and a placebo. All participants were 17 years of age or less and clinically healthy. Patients were enrolled by the twenty third week of gestation. The mean duration of calcium supplementation or placebo was approximately 14 weeks. Treatment consisted of 2.8 (+/- 1.5) tablets per day in the placebo group (N = 95) and 3.0 (+/- 1.4) tablets per day in the calcium group (N = 94). Dietary calcium intake was similar in both groups at about 1200 mg/day. The calcium group had a lower incidence of preterm delivery (less than 37 weeks; 7.4% vs 21.1%; p = 0.007); spontaneous labor and preterm delivery (6.4% vs 17.9%; p = 0.01); and low birth weight (9.6% vs 21.1%; p = 0.03). This effect was also present after stratified analysis by level of treatment compliance, urinary tract infection, and chlamydial infection. Life-table analysis demonstrated an overall shift to a higher gestational age in the calcium group compared with the placebo group (log rank test, p = 0.02). As suggested previously, the observed effect could be mediated by a reduction in uterine smooth muscle contractibility. If confirmed by future research, these results could represent an important preventive intervention for prematurity in high-risk populations. PMID- 2220916 TI - The association of intrapartum asphyxia in the mature fetus with newborn behavior. AB - A matched cohort study of mature newborns with biochemically determined intrapartum fetal asphyxia and mature newborns with normal blood gas and acid base assessments at delivery were studied to demonstrate the effect of fetal asphyxia on newborn behavior as expressed by the Brazelton newborn behavioral assessment scale. The newborn behavioral assessment scale was administered 3 days after delivery and again 2 weeks after delivery. The Lester newborn behavioral assessment scale summary scores for the group with asphyxia were of the same order as those in the control group. This was also true of the group of newborns with asphyxia with the more severe metabolic acidosis and those with low Apgar scores. These findings support the contention that many newborns who have undergone an intrapartum asphyxial insult will not have evidence of central nervous system injury and that the threshold of central nervous system injury is at the severe end of the spectrum of asphyxia as expressed by a metabolic acidosis. PMID- 2220917 TI - Sexually transmitted diseases and human immunodeficiency virus infection among women with pelvic inflammatory disease. AB - Both human immunodeficiency virus infections and pelvic inflammatory diseases are sexually acquired illnesses of great consequence to women. This study was undertaken to determine if women hospitalized with pelvic inflammatory disease, in a community endemic for human immunodeficiency virus, were at high risk to be infected with human immunodeficiency virus and if human immunodeficiency virus infections altered their hospital course. One hundred ten women hospitalized with pelvic inflammatory disease in Brooklyn (in a hospital in which 2% of parturients are human immunodeficiency virus seropositive) agreed to human immunodeficiency virus testing; 15 (13.6%) were found to be seropositive. Seropositive women were significantly more likely to have an admission white blood cell count less than 10,000/mm3 (p = 0.001). Human immunodeficiency virus seropositivity was not associated with a higher frequency of other sexually transmitted diseases although there was a trend toward more cases of syphilis among human immunodeficiency virus-infected women. Similarly, although there was no significant difference in rates of operative intervention (26.6% among seropositive and 8.4% among seronegative; p = 0.058), there was a trend toward more surgery among those who were human immunodeficiency virus infected. Women hospitalized with pelvic inflammatory disease, in a community endemic for human immunodeficiency virus, are at high risk for human immunodeficiency virus infection. More research is needed to verify a trend toward more refractory infections among human immunodeficiency virus-infected women. PMID- 2220918 TI - The natural history of thrombocytopenia associated with preeclampsia. AB - Sixty-one of 375 women with hypertension and preeclampsia in a 48-month period had thrombocytopenia. By postpartum day 3, 90% of these women had rising platelet counts, and by day 4, 59 of 61 women had counts greater than 100,000/mm3. The two exceptions had other pathologic conditions in addition to preeclampsia. Thrombocytopenia associated with preeclampsia should resolve by postpartum day 4. PMID- 2220920 TI - Pregnancy-induced hypertension and acute fatty liver of pregnancy: atypical presentations. AB - Severe pregnancy-induced hypertension and markedly elevated levels of serum alkaline phosphatase developed in a 29-year-old-woman in whom one pregnancy resulted in intrauterine death. Acute fatty liver of pregnancy developed with good fetal outcome in the next pregnancy. This case suggests that pregnancy induced hypertension and acute fatty liver of pregnancy are part of a clinical spectrum. Moreover, classic abnormalities of liver function tests need not be present in acute fatty liver of pregnancy. PMID- 2220919 TI - Continuing controversy in alloimmune thrombocytopenia: fetal hyperimmunoglobulinemia fails to prevent thrombocytopenia. AB - Two patients with severe alloimmune thrombocytopenia were managed by weekly intrauterine platelet transfusions at 25 to 36 weeks. In one patient high-dose immunoglobulin was also administered weekly to the mother, and high maternal and fetal immunoglobulin levels were achieved. Fetal platelet counts were similar in both patients. The only variable that affected fetal platelet concentration was the posttransfusion platelet count from the previous transfusion. PMID- 2220921 TI - Vibroacoustic stimulation and fetal behavioral state in normal term human pregnancy. AB - Vibroacoustic stimulation may affect human fetal behavior. Continuous graphic records of simultaneous ultrasonographic observations of fetal activities and electronic fetal heart rate tracings of 30 normal term fetuses were examined visually for the occurrence of behavioral state 30 minutes before and after 3 seconds of vibroacoustic stimulation. After vibroacoustic stimulation, the total time spent in state 1 decreased significantly, that spent in state 4 increased significantly, and times spent in state 2 and indeterminate state (no state established for at least 3 minutes) were unchanged. No fetus exhibited state 3 before or after vibroacoustic stimulation. State 4 occurred in 22 fetuses after vibroacoustic stimulation with a duration of at least 30 minutes in four fetuses, and was noted in all fetuses in pre-vibroacoustic stimulation state 1 and 11 of 16 fetuses in pre-vibroacoustic stimulation state 2. Fetal heart rate accelerations occurred within 10 seconds after vibroacoustic stimulation in 94% of the fetuses studied regardless of their prior behavioral state. The variation in the onset and duration of behavioral state responses in most fetuses after vibroacoustic stimulation may depend on previous behavioral state and could be important for interpretation of antenatal assessment that uses this stimulus. PMID- 2220922 TI - Successful conservative management of primary nonmetastatic cervical choriocarcinoma. AB - Primary cervical choriocarcinoma is a rare disease; since 1915 only about 60 cases have been published. The case presented here can be defined as primary cervical choriocarcinoma since it fulfills all the criteria delineated previously. PMID- 2220924 TI - Spontaneous infarction of placental chorioangioma and associated regression of hydrops fetalis. AB - We report a case of a large chorioangioma diagnosed prenatally with concomitant meconium peritonitis and hydrops fetalis in the second trimester. Spontaneous regression of the tumor occurred, associated with some resolution of the fetal hydrops and delivery near term with good neonatal outcome. PMID- 2220925 TI - Ovarian pregnancy: a report of twenty cases in one institution. AB - A series of 20 cases of primary ovarian pregnancy that were diagnosed and treated in one institution is reported. The prevalence rate of 1:3600 deliveries seems to be increasing in past years and comprises 3.3% of all extrauterine pregnancies. Clinical presentation, possible pathogenesis, diagnostic steps, preferred management, and future fertility are detailed. Inasmuch as all our 18 fertile patients used an intrauterine contraceptive device before the operation, special emphasis is made on the controversial relationship between use of intrauterine contraceptive devices and ovarian pregnancy. PMID- 2220923 TI - Effects of hypertension on pregnancy monitoring and results. AB - The effect of severity of hypertension on fetal heart rate tracing changes and neonatal outcomes was evaluated on all patients with hypertension seen in 1980 and 1981 (666 cases, 10% of the pregnant population) in the Chicago-Lying In Hospital. The patients were grouped according to severity of hypertension, and the fetal heart rate monitoring, drugs administered, mode of delivery, and neonatal outcome were analyzed. Half of the patients (326) had mild hypertension and 13% (87) had severe hypertension; the remainder (253) had moderate hypertension. There were 49% primiparous and 51% multiparous women. The diagnosis of preeclampsia was made in 76% of cases, and chronic hypertension in 19%. Only 12% of the total were premature by dates, but 47% of this group were among the severe group. Oxytocin was given to 50%, whereas delivery was spontaneous in 56% of cases, and by cesarean section in 22%. This was higher among the severe hypertension group (37%), and the prematurity rate was 47%. Nonstress testing was done in one third of cases and only nonreactivity was associated with neonatal death. Neonatal depression (Apgar score less than 6 at 5 minutes) was significantly associated with intrapartum fixed baseline and late decelerations; these were the best predictors of fetal outcome. The administration of magnesium sulfate, hydralazine, meperidine, or morphine did not predictably affect the fetal heart rate pattern. The perinatal mortality was 21% in the mild group and 36% and 138%, respectively, among moderate and severe cases of hypertension. Close antepartum and intrapartum surveillance, including proper fetal monitoring, should help to reduce risks for mother and fetus through timely intervention. PMID- 2220926 TI - Second-trimester ultrasonography: determinants of visualization of fetal anatomic structures. AB - Little information has been published regarding rates of visualization of fetal anatomic structures or factors affecting visualization in unselected patients. We prospectively studied these points by scoring visualization of intracranial, spinal, cardiac, ventral wall, umbilical cord, stomach, bladder, and genital anatomy in 573 consecutive midtrimester scans in which no fetal anomalies were seen. Each feature was scored 0, 1, or 2, corresponding to poor, adequate, or optimal visualization, and these eight numbers were summed for an overall visualization score. Overall visualization fell abruptly beyond maternal weight 165 pounds (p less than 0.001) and rose with advancing gestational age (p less than 0.001). Placental location did not significantly influence visualization. Overall, an adequate screening scan, defined as adequate visualization of central nervous system, heart, stomach, ventral wall, bladder, and cord was obtained in 51% of scans, and optimal visualization of each of these in only 9% of cases. Factors that might improve anatomic visualization and the implications of these results for the use of ultrasonography in screening for congenital anomalies are discussed. PMID- 2220928 TI - Postpartum osteomyelitis caused by group B streptococcus. AB - Postpartum infections caused by group B streptococci are generally limited in scope. We report a case of vaginal colonization with group B streptococcus that progressed in the postpartum period to osteomyelitis that necessitated total hip replacement. The patient had no risk factors predisposing to streptococcal osteomyelitis. An altered immune status in pregnancy and intrapartum bacteremia may be involved in the pathogenesis of this infection. PMID- 2220927 TI - Infertility and eating disorders. AB - Sixty-six consecutive infertility clinic patients were prospectively screened with the 26-item Eating Attitudes Test and a study questionnaire. Women identified as being at high risk for an eating disorder were then interviewed to confirm or refute the diagnosis. A total of 7.6% of infertility clinic women were found to suffer from anorexia nervosa or bulimia nervosa. If eating disorders not otherwise specified were included, a total of 16.7% of infertility patients were found to suffer from an eating disorder. Among infertile women with amenorrhea or oligomenorrhea 58% had eating disorders. Because women often fail to disclose eating disorders to their gynecologists and may appear to be of normal weight, it is recommended that a nutritional and eating disorder history be taken in infertility patients, particularly those with menstrual abnormalities. It has previously been shown that disorder eating and nutrition can affect menstruation, fertility, maternal weight gain, and fetal well-being. PMID- 2220929 TI - Antenatal spontaneous perforation of the extrahepatic biliary tree. AB - Spontaneous perforation of the biliary system is an unusual neonatal phenomenon that is rarely recognized at birth. To date, it has not been reported antenatally. A 16-year-old pregnant adolescent had an ultrasonogram at 25 weeks of pregnancy that revealed ascites in the fetus. After the infant was delivered at 32 weeks, a hepato-iminodiacetic acid scan showed a spontaneous rupture of the common bile duct. The infant was treated with external drainage of the biliary tree and recovered well. This case demonstrates that spontaneous perforations of the bile ducts can occur much earlier than the usually described 2 to 12 weeks after birth, can be diagnosed antenatally, and should be added to the list of causes of fetal ascites. PMID- 2220930 TI - Antenatal diagnosis of molybdenum cofactor deficiency. AB - Analysis of uncultured chorionic villus material from a woman at risk of fetus with sulfite oxidase deficiency revealed a deficiency of sulfite oxidase. This was confirmed on termination of the pregnancy. PMID- 2220931 TI - Preoperative evaluation of serum CA 125, TAG 72, and CA 15-3 in patients with endometrial carcinoma. AB - We evaluated 109 women with endometrial carcinoma to determine the accuracy of preoperative tumor-associated antigen levels (CA 125, CA 72, CA 15-3) for prediction of extrauterine disease and whether TAG 72, CA 15-3, or both would improve the predictive value of CA 125 alone. Eleven (12%) of 80 patients with disease confined to the uterus or positive cytologic findings had CA 125 values greater than 35 U/ml versus 12 (65%) of 20 patients with extrauterine metastasis. Therefore CA 125 values had sensitivity of 65% and specificity of 88%. The TAG 72 level was elevated (greater than 6 U/ml) in 4% of patients with localized disease and 30% with metastasis. CA 15-3 was elevated (greater than 30 U/ml) in 17% and 65% in these categories, respectively. TAG 72 or CA 15-3 levels did not improve the combination of sensitivity and specificity of CA 125 alone. In addition, only one of 10 patients with microscopic metastasis (three cases) or positive peritoneal cytology (seven) had elevation of any of these tumor-associated antigen levels. Failure to detect occult metastasis and a high false-positive rate limit the role of these tumor-associated antigen assays in the preoperative evaluation of patients with endometrial carcinoma. PMID- 2220933 TI - The effect of race on the relationship between fetal death and altered fetal growth. AB - This population study examines racial differences in the relationship between birth weight and fetal death. An earlier report showed that a birth weight that results in a fourfold increased risk of stillbirth is not a constant birth weight percentile (2nd percentile at 25 weeks, 17th percentile at 42 weeks). This analysis was applied to 782,430 white and black births in Illinois from 1980 to 1984. Mean and 10th percentile growth for white and black infants is identical before 34 weeks' gestation and growth diverges by 250 gm at term, with white infants being larger. Race-specific birth weights resulting in quadrupling of the stillbirth rate were determined with an exponential regression analysis of the relationship between birth weight and fetal death rate for each gestational age. The data indicate (1) that the birth weights resulting in quadrupling the stillbirth rate are substantially above the Denver 10th percentile and the previously unpublished race-specific Illinois 10th percentiles and (2) that at term white infants demonstrate this constant risk at the 12th percentile, whereas black infants exhibit the risk at the 18th percentile. From these data we conclude that black fetuses are more sensitive than white fetuses to factors that adversely affect growth and that continued use of "race-neutral" data for clinical management in racially heterogenous populations will not accurately predict the risk of stillbirth. PMID- 2220934 TI - Effects of intravascular fetal blood transfusion on fetal intracardiac Doppler velocity waveforms. AB - In 12 fetuses from pregnancies with red blood cell isoimmunization Doppler velocity waveforms were recorded at the level of atrioventricular valves immediately before and at 15-minute intervals for 2 hours after the intravascular transfusion. The left and right cardiac outputs, the ratio between the peak velocities during early passive ventricular filling and active atrial filling at the level of both ventricles as well as the heart rate were calculated. Before transfusion, the left and right cardiac outputs were significantly higher than reference ranges for gestation that were constructed from the cross-sectional study of 187 normal pregnancies. After transfusion there was a significant temporary fall in right and left outputs associated with increased ratios between the peak velocities during early passive ventricular filling and active atrial filling. Within 2 hours after transfusion both parameters returned toward the normal range. In addition, no significant changes were found for fetal heart rate values before and after transfusion. The fall of cardiac output was significantly related to the amount of expansion of the feto-placental volume. PMID- 2220932 TI - High infectious morbidity in pregnant women with insulin-dependent diabetes: an understated complication. AB - Patients with insulin-dependent diabetes are prone to infection, possibly related to poor metabolic control. Relative immune deficiency exists in pregnancy. We hypothesized that pregnant patients with insulin-dependent diabetes are at an increased risk for infection and that infection is related to poor glycemic control. We matched 65 pregnant women with insulin-dependent diabetes to 65 nondiabetic pregnant controls. At least one episode of infection before delivery occurred in 83% of the women with insulin-dependent diabetes (26% in control group). The rate of postpartum infection was five times higher in the group with insulin-dependent diabetes and they were susceptible to more kinds of infections. Although there was no overall difference among the indices of glycemic control, hemoglobin A1 obtained before the infection was higher than during infection. We conclude that a high rate of infection exists in pregnant women with diabetes; infection and poor glycemic control may be associated, but it is unclear whether improvement in metabolic control will reduce this high infection rate. PMID- 2220935 TI - Human fetal foramen ovale flow velocity waveforms relative to behavioral states in normal term pregnancy. AB - In 16 normal pregnancies the relationship between foramen ovale flow velocity waveforms and fetal behavioral states at 37 to 38 weeks' gestation was studies with Doppler techniques. Foramen ovale flow velocity waveforms are characterized by a typical systolic/diastolic component. Average flow velocity was statistically significantly increased in behavioral state 2F (active sleep) as compared with state 1F (quiet sleep), which was mainly determined by an increase in flow velocity during the end-systolic and passive atrial filling phase. The increase in the average flow velocity at the foramen ovale level during active sleep suggests a redistribution of blood flow at the cardiac level, resulting in an increased right-to-left shunt. PMID- 2220936 TI - Suppression of serum insulin level by diazoxide does not alter serum testosterone or sex hormone-binding globulin levels in healthy, nonobese women. AB - Suppression of serum insulin levels with diazoxide is associated with a decrease in serum testosterone and an increase in serum sex hormone-binding globulin in obese women with the polycystic ovary syndrome. To determine whether physiologic insulin levels play a regulatory role in the androgen status of nonobese women with normal menses, the androgen status of five nonobese normal women was assessed on two occasions: during a control study and after 10 days of oral diazoxide (100 mg, three times daily) administration. Insulin release in response to 100 gm oral glucose administration decreased from 108.0 +/- 28.2 to 49.3 +/- 5.2 nmol.min/L (p = 0.05) after diazoxide administration. However, despite suppression of insulin release, diazoxide administration did not affect serum total testosterone (diazoxide, 0.73 +/- 0.10; control, 0.69 +/- 0.11 nmol/L; p = NS) or sex hormone-binding globulin (diazoxide, 79.7 +/- 16.6; control, 70.2 +/- 12.6 nmol/L; p = NS) concentrations. These observations suggest that physiologic insulin levels in nonobese healthy women do not regulate testosterone metabolism and that diazoxide does not exert a direct or independent effect on serum testosterone or sex hormone-binding globulin levels. PMID- 2220937 TI - Intrapartum uterine rupture and inflammatory bowel disease. AB - The incidence of uterine rupture in pregnant women ranges from 0% to 1.1% in large series. This case report describes a woman with a history of obstetric complications, uterine rupture, and active inflammatory bowel disease that was treated with high-dose prednisone. PMID- 2220938 TI - Pelvimetry by magnetic resonance imaging in breech presentation. AB - Evaluation of the pelvis by pelvimetry plays an important role in selecting patients with term breech presentation for possible vaginal delivery. X-ray pelvimetry involves the disadvantage of fetal exposure to ionizing radiation. Computed tomography reduces the amount of radiation markedly, but there is still a risk. Ten patients with breech presentation at term underwent antepartum pelvimetry with magnetic resonance imaging, following by postpartum magnetic resonance pelvimetry and x-ray pelvimetry. Measurements with magnetic resonance imaging are as reliable as those obtained with x-ray pelvimetry and the contrast of the magnetic resonance images is even better. The advantages of magnetic resonance pelvimetry are clear: no ionizing radiation and reliable pelvimetry results in cases of term breech presentation in which a normal pelvis is a prerequisite for safe vaginal delivery. PMID- 2220939 TI - Intraamniotic infection in the very early phase of the second trimester. AB - A total of 157 consecutive patients were studied in an effort to examine prospectively the incidence of asymptomatic intraamniotic infection in the early phase of the second trimester. All patients were referred for amniotic fluid karyotyping. In addition, the amniotic fluids were examined for Gram stain and were directly cultured on blood agar and MacConkey agar as well as in thioglycollate broth. We found positive amniotic fluid cultures in eight cases (5.09%); however, results of Gram stain examinations were negative in all amniotic fluid samples. The data indicate that there is no correlation between white blood cells in the amniotic fluid and positive amniotic fluid culture results. Only one pregnancy with positive amniotic fluid culture resulted in a septic abortion. Therefore we can suggest that intraamniotic infection can exist early in pregnancy, even with intact membranes, and in most cases without any clinical symptoms. PMID- 2220940 TI - Placental histology in fetuses between 18 and 23 weeks' gestation with abnormal karyotype. AB - Placentas from karyotypically abnormal fetuses (18 to 23 weeks' gestation) were analyzed prospectively at the light microscopic level. Group I consisted of 14 control placentas. Group II consisted of 14 placentas from fetuses with an abnormal karyotype. Secondary and tertiary stem villi counts, small muscular artery counts, and total vessel counts were determined per 100 x field. There were no differences in secondary and tertiary stem villi counts between groups. A significant decrease in small muscular artery counts (p less than 0.01) and total vessel counts (p less than 0.01) was noted in group II. Placental and fetal weights were comparable between groups. This undervascularization may represent placental immaturity as a result of arrested or delayed angiopoiesis. It appears that this abnormality is established before the third trimester and may be enhanced by late vascular obliteration as reported by others. These data substantiate the concept that the structure and function of the placenta is determined to a great degree by fetal karyotype and may help explain the morbidity and mortality seen in these fetuses. PMID- 2220942 TI - Autologous antibodies eluted from membrane fragments in human ovarian epithelial neoplastic effusions. III. Cytotoxic potential in vitro and characterization of antigen(s). AB - Cyst and ascites fluids from patients with ovarian epithelial neoplasms contain immunoglobulins with antitumor activity. Autologous antibodies bound to the cellular membrane fragments obtained from human ovarian neoplastic effusions react with cell-surface antigens on different human ovarian cell lines, surgical specimens of human ovarian adenocarcinoma, and human ovarian tumors grown in athymic Balb/c mice. The antibodies do not react with tissue preparations from normal human ovaries, other nonovarian normal or neoplastic tissues, and nonovarian human cell lines. These studies indicate that these antibodies are capable of complement-mediated lysis of human ovarian tumor cell lines in vitro. Preliminary characterization of the autologous ovarian tumor-associated antigen(s) indicates that it may be composed of three large-molecular-weight proteins of 182,000, 164,000, and 122,000 d. PMID- 2220941 TI - Collagen metabolism in gynecologic patients: changes in the concentration of the aminoterminal propeptide of type III procollagen in serum. AB - We have previously found the serum concentration of the aminoterminal propeptide of type III procollagen, an indicator of collagen metabolism, to be increased in advanced ovarian cancer. In this study we measured the serum aminoterminal propeptide of type III procollagen concentration in healthy women during the menstrual cycle and in patients with salpingo-oophoritis, leiomyomas, endometriosis, and benign ovarian tumors. The concentration was higher in the luteal phase than that in the follicular phase, suggesting an association of collagen metabolism with ovarian steroid hormones. Severe salpingo-oophoritis increased the serum level of the aminoterminal propeptide of type III procollagen with a decrease to normal during recovery. Elevated values were occasionally seen in endometriosis and leiomyomas. These findings indicate that the aminoterminal propeptide of type III procollagen is a relatively unspecific indicator of ovarian carcinoma. PMID- 2220944 TI - A progesterone-induced blocking factor corrects high resorption rates in mice treated with antiprogesterone. AB - Earlier we showed that because of the presence of functional progesterone receptors, lymphocytes of healthy pregnant women produced an immunomodulatory protein in the presence of progesterone, whereas those of nonpregnant persons did not. Progesterone-treated murine pregnancy lymphocytes release a similar factor. The present study reveals the biologic significance of this finding. Treatment of BALB/c mice that were 8 days pregnant with a progesterone receptor blocker (RU 486) resulted in 100% resorption of the fetuses. Simultaneous administration of the supernatant from progesterone-treated murine pregnancy spleen cells restored the resorption rate to the original 6% observed in untreated control animals. These data suggest that functional lymphocytic progesterone binding sites are needed for the maintenance of normal pregnancy. Because of the blockage of progesterone receptors and the consequent inability of the lymphocytes to produce the progesterone-induced blocking factor, abortion is initiated by immune factors. The fact that administration of the preformed blocking factor counteracted the effect of antiprogesterone treatment suggests that progesterone mediated immunosuppression is needed for the maintenance of normal gestation. PMID- 2220943 TI - Hypoxic acidemia, hyperviscosity, and maternal hypertension do not affect the umbilical arterial velocity waveform in fetal sheep. AB - The effect of hypoxic acidemia, hyperviscosity, and maternal hypertension on the umbilical arterial velocity waveform was studied in 23 chronically catheterized fetal sheep. Fetal hypoxic acidemia induced by lowering the maternal inspired oxygen concentration (n = 7) caused no change in the ratio of systolic/diastolic blood velocity even when fetal arterial pH was as low as 6.8. Fetal blood hyperviscosity (n = 7) induced by exchange transfusion with packed maternal blood cells increased placental vascular resistance by greater than or equal to 50% but had no significant effect on the systolic/diastolic ratio. Similarly, maternal hypertension induced by intravenous infusion of angiotensin II to the ewe (n = 9) did not affect the systolic/diastolic ratio despite a 50% increase in maternal arterial blood pressure. We conclude that umbilical arterial velocity waveform abnormalities observed in growth-restricted human fetuses are probably not a direct result of fetal hypoxemia or hyperviscosity or maternal hypertension. PMID- 2220945 TI - Vasodilatory effects of nifedipine, methoxyverapamil, and sodium nitroprusside on contractile responses of the ewe uterine artery at term pregnancy. AB - The differential inhibitory effect of the vasodilators on contractile responses to norepinephrine, serotonin, and potassium on isolated uterine artery ring segments from pregnant ewes within 2 weeks of term was quantified and correlated with the source of Ca++ for the vasoconstrictors producing the smooth muscle contraction. The contraction evoked by the vasoconstrictors was dependent on extracellular Ca++ and in agonist-induced contractions also on an intracellular pool of Ca++. Nifedipine effectively inhibited K(+)-induced (90 mmol/L) contractions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 1.95 +/- 0.9 x 10(-8) mol/L), whereas it was relatively ineffective in blocking norepinephrine-induced (10(-5) mol/L) or serotonin induced (10(-5) mol/L) vasoconstriction (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 1.38 +/- 0.4 x 10(-4) mol/L and 2.04 +/- 0.4 x 10(-5) mol/L, respectively). Methoxyverapamil (D-600) strongly inhibited serotonin-induced contractions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 3.3 +/- 0.3 x 10(-7) mol/L). The phasic rather than the tonic components of the serotonin- and norepinephrine induced contractions were more effectively inhibited by D-600 (p less than 0.05). Sodium nitroprusside preferentially blocked (p less than 0.05) the sustained tonic components of norepinephrine- and serotonin-induced vasoconstrictions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 7.1 +/- 0.4 x 10(-7) mol/L and 8.2 +/- 0.6 x 10(-7) mol/L, respectively). On the basis of these findings it is concluded that D-600 and sodium nitroprusside are more effective than nifedipine in blocking contractile responses due to receptor stimulation, and therefore might be more effective in the treatment of hypertensive emergencies in which these amines might be implicated. PMID- 2220947 TI - Long-term maternal-fetal exposure to high-low insulin concentrations alter liver but not brain insulin receptors. AB - We investigated the effects of long-term (5 to 6 days) in vivo exposure to hyperinsulinemia and hypoinsulinemia on maternal and fetal rat (18 to 20 days' gestation; term approximately 21 days) brain and liver insulin receptors. Further we studied the in vitro effects of long-term insulin exposure on cultured rabbit neuronal cell insulin receptors. Long-term glucose infusions to maternal rats resulted in maternal and fetal hyperglycemia and mild hyperinsulinemia, which decreases the liver insulin receptor abundance of the mother but increased that of the fetus. Streptozotocin-induced maternal diabetes resulted in maternal and fetal hyperglycemia with hypoinsulinemia (or near-normal insulin levels) and increased maternal and fetal liver insulin receptors. The maternal and fetal brain insulin receptor abundance failed to change at high or low insulin concentrations. Similarly long-term insulin (5 micrograms/ml) exposure failed to alter cultured neuronal cell insulin receptors as well. We conclude that perturbations in maternal and fetal circulating insulin concentrations fail to affect the brain insulin receptors. This protective phenomenon may be critical in maintaining the normal neuronal energy balance and functioning during certain disease states such as diabetes mellitus and hyperinsulinism. PMID- 2220946 TI - Fetal and maternal response to intravenous infusion of a thromboxane synthetase inhibitor. AB - Pharmacologic inhibition of thromboxane synthetase activity has reversed the clinical manifestations of toxemia in the ovine model. To investigate placental transfer and fetal effects of a selective thromboxane synthetase inhibitor, CGS13080 (Ciba-Geigy, Summit, N.J.) was intravenously infused into eight singleton- or twin-bearing ewes near term. During CGS 13080 infusion (0.1 mg/kg/hr), maternal steady-state CGS 13080 levels of 102 +/- 18 ng/ml were achieved within 30 minutes and maternal serum thromboxane generation decreased significantly (13 +/- 3 to 4 +/- 1 ng/ml). However, fetal serum levels of CGS 13080 were only 4% of peak maternal concentrations and fetal serum thromboxane generation did not change. There was no evidence of change in uterine blood flow, maternal or fetal blood pressure, heart rate, blood gas values, or fetal or maternal metabolites of prostacyclin or prostaglandin E2 during the study. We speculate that CGS 13080 may be efficacious in the treatment of human pregnancy induced hypertension. PMID- 2220949 TI - Definition of fetal asphyxia. PMID- 2220948 TI - Venous and hepatic vascular responses to indomethacin and prostaglandin E1 in the fetal lamb. AB - Evidence is accumulating that prostaglandins affect the tone of the ductus venosus. Therefore prostaglandins might alter the distribution of umbilical venous return between the ductus venosus and liver. We have examined the effect of indomethacin and prostaglandin E1 on the vascular resistance of the umbilical placental circulation, ductus venosus, and liver in 14 chronically instrumented fetal lambs. We found that indomethacin caused a nearly twofold increase in the vascular resistance of both the ductus venosus and liver. Prostaglandin E1, administered 70 minutes after indomethacin at a dose of 0.41 +/- 0.09 (SEM) micrograms/min per kilogram of fetal weight, decreased umbilical-placental blood flow, increased the vascular resistance of the umbilical arteries and placenta, and reversed the elevation of the vascular resistances of the ductus venosus and liver. Because both indomethacin and prostaglandin E1 affected the resistances of the ductus venosus and liver to the same extent, it is unlikely that prostaglandins of the E series mediate the change in distribution of umbilical venous return between the ductus venosus and liver during fetal stress. PMID- 2220950 TI - Cocaine effects on fetal behavioral state. PMID- 2220951 TI - Possible therapeutic applications of cordocentesis. PMID- 2220952 TI - Serum levels of interleukin-2 and tumor necrosis factor-alpha in women with recurrent abortion. PMID- 2220953 TI - What is birth asphyxia? PMID- 2220954 TI - Embryo migration responsible for ectopic pregnancies. PMID- 2220955 TI - Responsibility expands to extended family members. PMID- 2220956 TI - Does prophylactic amnioinfusion make a difference. PMID- 2220957 TI - Cordocentesis and immune thrombocytopenia--continued. PMID- 2220958 TI - Measures of test performance and predictive values. PMID- 2220959 TI - Toxicity of vancomycin given during pregnancy. PMID- 2220960 TI - Ethics of new reproductive technologies. PMID- 2220961 TI - Twin transfusion syndrome. PMID- 2220962 TI - Oral contraceptives and breast cancer. AB - Among women in general the risk of breast cancer through 59 years of age does not appear to be affected appreciably by the use of oral contraceptives. Nonetheless, concern continues to be expressed about the effects of early age at first use, long-term duration of use, formulation, and a variety of other factors thought to influence breast cancer risk in the presence of oral contraception. A number of recent studies restricted to young women suggest that long-term use may increase the risk of disease occurring very early, but the present lack of consistent findings in well-conducted epidemiologic studies prevents any certain conclusion with regard to cause-and-effect. However, if an increased risk were indeed present, the most plausible interpretation is that long-term oral contraception promotes earlier clinical manifestation of breast cancer in some women while having no net impact on their lifetime risk of the disease. PMID- 2220964 TI - Oral contraceptives and myocardial infarction. AB - The risk of myocardial infarction in contraceptive users is limited to women over 35 years of age who smoke. The cause of myocardial infarction in oral contraceptive users is thrombotic and not atherosclerotic. Minor lipid changes have no clinical relevance to myocardial infarction in contraceptive pill users and do not appear to increase coronary plaques. PMID- 2220965 TI - Clinical acceptability of monophasic gestodene. AB - The monophasic low-dose contraceptive containing 30 micrograms of ethinyl estradiol and 75 micrograms of gestodene has been tested in numerous clinical studies to determine contraceptive reliability, cycle control, and influence on metabolism and to uncover concomitant symptoms. Clinical data have been derived from continuous phase III studies. Now that the preparation has been introduced in several countries, the opportunity to assemble comprehensive experience has been taken by initiating phase IV studies. Documentation on 600,000 therapy cycles with monophasic gestodene among 100,000 women is already available. The drop-out rate was low. A large number of women participated in the clinical studies for a long time--some up to 3 years. Study results showed that contraceptive reliability was high and cycle control was excellent. The gestodene combination was well tolerated. The frequency of concomitant symptoms was low. The monophasic gestodene meets the basic criteria essential for an oral contraceptive. PMID- 2220963 TI - Oral contraceptives, lipoproteins, and atherosclerosis. AB - A nonhuman primate model was developed to study the effects of oral contraceptives on lipoproteins and atherosclerosis. Cynomolgus macaques were selected because of their susceptibility to diet-induced atherosclerosis and because their reproductive physiology, menstrual cycle, and circulating sex hormone patterns are similar to those of human females. The first study compared a vaginal ring containing levonorgestrel and estradiol with an oral contraceptive containing norgestrel and ethinyl estradiol. A second study compared two oral combinations: norgestrel-ethinyl estradiol and ethynodiol diacetate-ethinyl estradiol. As predicted, use of all the contraceptives led to lowering of high density lipoprotein cholesterol levels. However, contrary to what might be expected, use of the ethinyl estradiol-containing oral contraceptives did not lead to an increase in the prevalence or extent of atherosclerosis. We concluded that ethinyl estradiol neutralized the atherogenic influence of the progestin component of oral contraceptives. PMID- 2220966 TI - Pharmacokinetics of gestodene and ethinyl estradiol after oral administration of a monophasic contraceptive. AB - The pharmacokinetic and protein-binding properties of gestodene and ethinyl estradiol have been investigated after single and multiple dosing in several studies in 83 healthy, young women. After oral administration, gestodene is completely absorbed and bioavailable and exhibits dose-linear pharmacokinetics. During long-term pill use, serum levels of gestodene were four to five times higher than after single administration, showing a periodic increase from day 1 to day 10 during each cycle. Ultrafiltration studies revealed that 75.3% of total serum gestodene is bound to sex hormone-binding globulin, 24.1% is bound to albumin, and only 0.6% is not protein bound. Thus gestodene levels during steady state are explained by an increase in sex hormone binding-globulin as a result of concomitant administered ethinyl estradiol and a specific binding of gestodene to this protein. Serum levels of ethinyl estradiol during single and multiple administration were identical and were not different from those observed with another preparation containing 30 micrograms of ethinyl estradiol. PMID- 2220968 TI - Crohn's disease and retinal vascular disease. AB - Patients with Crohn's disease may manifest extraintestinal findings including ocular involvement. We treated two patients with Crohn's disease who manifested retinal vascular disease that may have been related to the immune nature of the underlying disease or possibly to changes in the vasculature or coagulation system. One patient had a central retinal vein occlusion and the other had retinal vasculitis involving retinal arteries and veins with an apparent branch retinal artery occlusion. Both patients were in excellent health except for Crohn's disease, which was confirmed by a biopsy specimen. In one patient, the diagnosis of retinal vasculitis preceded the clinical diagnosis of Crohn's disease, whereas for the second patient the symptomatology of the intestinal disease preceded the ocular manifestations. We suggest that inflammatory bowel disease should be considered in the differential diagnosis of retinal vascular occlusive disease, especially in a young patient. PMID- 2220967 TI - Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome. AB - Two patients, both seropositive for the human immunodeficiency virus, developed rapidly progressive retinal necrosis associated with a systemic herpes zoster infection. The retinitis in these patients was characterized by primary involvement of the outer retina, with sparing of the inner retina and retinal vasculature until late in the disease process; a rapidly progressive course; poor response to intravenous acyclovir; and development of rhegmatogenous retinal detachment. In one of the patients, the retinitis was initially multifocal. Electron microscopy of a retinal biopsy specimen from one of the patients demonstrated virus particles consistent with a herpesvirus, and polymerase chain reaction disclosed herpesvirus in a retinal biopsy specimen of the other patient. This entity may represent a distinct form of acute retinal necrosis that is seen in immunocompromised individuals. PMID- 2220969 TI - Vitrectomy retinotomy aspiration biopsy of choroidal tumors. AB - We used an investigational technique for the biopsy of intraocular tumors to aid in the diagnosis of three choroidal tumors. A three-port trans-pars plana vitrectomy was performed in conjunction with retinotomy, tumor biopsy, endophotocoagulation, and air-fluid exchange. Vitrectomy was used to decrease the amount of traction secondary to retained vitreous after intraocular surgery. Retinotomy sites were chosen under microscopic control to avoid large caliber retinal vessels. Then a modified tumor-aspiration technique, together with endophotocoagulation and aspiration of intraoperative vitreous hemorrhages, provided an opportunity to sample tumor tissue continually at varied depths. We have added standard vitreous surgery concepts, techniques, and instrumentation to produce vitrectomy retinotomy aspiration biopsy of choroidal tumors. PMID- 2220970 TI - Magnetic resonance imaging in the evaluation of vitreoretinal disease in eyes with intraocular silicone oil. AB - Media opacification in eyes filled with silicone oil makes the evaluation of recurrent retinal detachment difficult. Ultrasonography through silicone oil is subject to significant imaging artifacts. We performed magnetic resonance imaging on six patients with unilateral intravitreal silicone oil to determine if the technique would detect detached retina and subretinal oil. All patients had undergone pars plana vitrectomy with silicone oil injection for proliferative vitreoretinopathy; five patients had encircling solid silicone scleral buckles. In five patients the media were clear, and ophthalmoscopic findings were correlated with magnetic resonance findings. Four patients had recurrence of inferior retinal detachment; magnetic resonance imaging demonstrated subretinal oil in three of these patients. One patient had a concentric, shallow, anterior retinal detachment; magnetic resonance scanning demonstrated a globular hyperintensity suggestive of subretinal oil. In the sixth patient, who had an opaque cornea, magnetic resonance imaging suggested that the retina was attached preoperatively; this was confirmed at subsequent surgery. A chemical shift artifact was helpful in defining the contour of retinal detachments and the presence of subretinal oil by outlining the silicone oil within the eye. PMID- 2220971 TI - Histopathologic study of the Molteno glaucoma implant in three patients. AB - Three eyes with the Molteno glaucoma implant (one eye with epithelial downgrowth, one eye with iridocorneal endothelial syndrome, and one eye with aphakia and glaucoma) were enucleated two to six years after implantation. Histopathologic examinations disclosed no evidence of erosion of sclera or conjunctiva of the eye by the glaucoma implant device. In the outer layers of the bleb wall, few and mostly degenerated inflammatory cells were present, which represented a minimal inflammatory reaction. Scanning electron microscopy of the tubes in these three patients showed that the tube was intact, patent, and without signs of degradation. The tube entering into the anterior chamber caused no appreciable inflammation and maintained its patency even when downgrowth epithelial cells lined the anterior chamber. The Molteno plate induced little or no inflammatory reaction. Therefore, the Molteno glaucoma implant is a useful device for patients with high risk for failure after surgery for glaucoma. PMID- 2220972 TI - Correlations of acoustic tissue typing of malignant melanoma and histopathologic features as a predictor of death. AB - Forty-six eyes with uveal melanoma were scanned with a computerized diagnostic ultrasound system before enucleation, and light microscope sections were obtained. Tumors were characterized by ultrasonically measured dimensions and power spectrum analysis, which provided information not available in conventional A- or B-scan ultrasonography. Histopathologic features, including cell clustering pattern, cell type, pigmentation, vascularity, and necrosis, were quantified. Statistically significant correlations were found between parameters derived from the power spectrum and histologic characteristics. Patients were followed up for up to ten years with 14 deaths occurring because of metastases. Using a Cox relative risk model with histopathologic data, a risk model comprising pigmentation and cell type (P less than .0001) was obtained. Using ultrasonic characteristics, a model comprising tumor volume and scatterer concentration (P = .0062) was obtained. The results suggest that ultrasonic tissue characterization and three-dimensional biometry may provide improved in vivo prognostic indicators for uveal melanoma. PMID- 2220973 TI - Magnetic resonance imaging of radiation optic neuropathy. AB - Three patients with delayed radiation optic neuropathy after radiation therapy for parasellar neoplasms underwent magnetic resonance imaging. The affected optic nerves and chiasms showed enlargement and focal gadopentetate dimeglumine enhancement. The magnetic resonance imaging technique effectively detected and defined anterior visual pathway changes of radionecrosis and excluded the clinical possibility of visual loss because of tumor recurrence. PMID- 2220975 TI - Successful treatment of recurrent corneal erosion with Nd:YAG anterior stromal puncture. AB - I used a new technique to create anterior corneal stromal punctures for the treatment of traumatic recurrent corneal erosions that had not responded to conventional therapy. Three patients with such erosions within the visual axis were successfully treated by using multiple applications of the Nd: YAG laser set at energy levels between 1.8 and 2.2 mJ. One of these patients had previous stromal puncture with a bent 25-gauge needle. The erosions of all patients healed without complications and have remained symptom-free for four to six months. Compared with needle puncture, the laser punctures were more reproducible, shallow, and translucent. PMID- 2220974 TI - Successful medical management of Acanthamoeba keratitis. AB - Seven patients with documented Acanthamoeba keratitis were treated with prolonged and intensive triple antiamoebic therapy consisting of topical neomycin-polymyxin B-gramicidin, propamidine isethionate 0.1%, and miconazole nitrate 1%. Additionally, five patients were treated with topical corticosteroids. Six of seven patients were cured of Acanthamoeba keratitis with medical therapy alone, one patient required therapeutic penetrating keratoplasty to eradicate the infection. Two patients underwent penetrating keratoplasty to improve their vision after medical therapy. Our series differs from previous reports in that triple antiamoebic therapy was used in all seven patients and was successful in both early and advanced cases of Acanthamoeba keratitis. Prolonged and intensive topical therapy with these three antiamoebic drugs may be an effective mode of therapy for Acanthamoeba keratitis. PMID- 2220976 TI - Penetrating keratoplasty after ocular trauma. AB - We reviewed the records of 41 patients who underwent penetrating keratoplasty for a corneal opacity caused by trauma between Jan. 1, 1983, and Dec. 31, 1988. Most of the patients were young males whose average age was 35 years. Common tools accounted for many injuries (14 of 41, 34%). Sixteen injuries (39%) were work related. Thirty-six patients (88%) had corneal scars from a perforating injury, four patients (10%) had corneal edema, and one patient (2%) required emergency penetrating keratoplasty for extensive tissue loss. Of the 39 patients with one year of follow-up, 31 (82%) maintained clear corneal grafts. Rejection occurred in nine of 39 patients (23%) and only three (33%) of the rejections resolved. Visual outcome was favorable with 20 patients (51%) attaining best-corrected postoperative visual acuity of 20/20 to 20/40, nine patients (23%) attaining visual acuity of 20/50 to 20/100, and ten patients (26%) attaining visual acuity of 20/200 or worse. Preoperative retinal disease (six of 39, 15%), astigmatic errors (five of 39, 13%), graft failures (four of 39, 10%), and postoperative glaucoma (12 of 39, 31%) adversely influenced the outcome. Although the prevalence of postoperative complications is relatively high, good visual results can be obtained in patients who undergo penetrating keratoplasty after ocular trauma. PMID- 2220977 TI - Limbal autograft reconstruction after conjunctival squamous cell carcinoma. AB - Two patients who had squamous cell carcinoma with extensive limbal and corneal involvement were treated with surgery and cryotherapy. Rarely large areas of the cornea are involved by this tumor. Visual prognosis in such patients is poor. In these two patients, autologous limbal transplants were effective in restoring an excellent corneal surface and good visual function. This technique may be useful in the reconstruction of eyes with extensive neoplastic involvement of the corneoscleral limbus and cornea. PMID- 2220978 TI - Response of Bitot's spots in preschool children to vitamin A treatment. AB - In a double-masked, placebo-controlled, clinical trial in Indonesia, 88 preschool children between the ages of 36 and 72 months with Bitot's spots were randomly assigned to 200,000 IU of oral vitamin A or placebo and followed up for five weeks. Baseline and follow-up serum vitamin A levels were obtained. Of the 45 children receiving vitamin A, 33 (73.3%) showed complete cure and disappearance of Bitot's spots, six (13.3%) had disappearance of some but not all Bitot's spots, and six (13.3%) were unresponsive to treatment. The nonresponsive children were older, all male, and had higher initial mean serum vitamin A levels, 23.0 micrograms/dl, compared to 15.9 micrograms/dl in the cured group (P = .017). These data suggest that normal vitamin A status may be found in approximately 13% of children with Bitot's spots before vitamin A intervention and that one fourth of those who had Bitot's spots originally will not be cured of all Bitot's spots after intervention. These are important factors to consider when using Bitot's spots in prevalence surveys as a clinical sign of vitamin A deficiency. PMID- 2220979 TI - Facial nerve injury and hemifacial spasm. AB - We studied evidence of facial nerve damage in patients with hemifacial spasm. Three types of evidence of nerve damage were analyzed: objectively measured weakness in eyelid protractor strength, clinically evident weakness of muscles innervated by the seventh nerve, and clinically evident aberrant seventh nerve regeneration. Of the 60 patients in the study, 54 (90%) had at least one of these features of seventh nerve damage. Objectively measured eyelid protractor weakness was noted in 27 of 58 patients (47%) who were tested. Clinically apparent weakness of at least one of four facial muscle groups was noted in 42 of 60 patients (70%). Aberrant seventh nerve regeneration was documented in 25 of 60 patients (42%). These findings indicate that facial nerve damage is common in patients with hemifacial spasm. PMID- 2220980 TI - Multifocal intraocular lenses--better or worse? PMID- 2220981 TI - National Registry of Drug-Induced Ocular Side Effects. PMID- 2220982 TI - Nd:YAG treatment of a posterior vitreous cyst. PMID- 2220983 TI - Argon laser photocoagulation for advanced retinopathy of prematurity. PMID- 2220984 TI - Retinoscopy with a bent filament. PMID- 2220985 TI - A simple method for detection of hemianopsia or quadrantanopsia. PMID- 2220986 TI - Demographic patterns and academic choices of graduates of one ophthalmology training program. PMID- 2220987 TI - Congenital myopia in Stickler's hereditary arthro-ophthalmopathy. PMID- 2220988 TI - Systemic neurocristopathy associated with Rieger's syndrome. PMID- 2220989 TI - Sixth nerve palsy as the initial manifestation of sarcoidosis. PMID- 2220990 TI - Unsuspected renal cell carcinoma metastatic to the choroid nine years after nephrectomy. PMID- 2220991 TI - Progressive optic atrophy and the primary antiphospholipid antibody syndrome. PMID- 2220992 TI - Acute dacryocystitis caused by Pasteurella multocida. PMID- 2220993 TI - Keratitis associated with Pseudomonas mesophilica in a patient taking topical corticosteroids. PMID- 2220994 TI - Nocardia scleritis. PMID- 2220995 TI - The effects of education on hand use with industrial workers in repetitive jobs. AB - Eighteen subjects participated in a preliminary study to determine the effects of two types of educational programs on the hand-use patterns of industrial workers at risk for developing cumulative trauma disorder (CTD). The subjects were divided into three groups: Two groups received different educational programs and the third group served as the control. One program used a handout as the only educational tool; the other used the handout as well as a hands-on demonstration of the concepts in the handout. Pretests and posttests of the frequency of movements identified with CTD of the hand and wrist during work were administered to all subjects. Both educational programs were significantly effective in reducing the number of at-risk movements performed by workers tested 1 week after receiving the education. No significant difference was found between the two educational programs. The results of this study show that education can affect hand-use patterns, and a similar study on a larger sample is recommended. PMID- 2220996 TI - The Test of Orientation for Rehabilitation Patients: interrater reliability. AB - The Test of Orientation for Rehabilitation Patients (TORP) (Deitz, Beeman, & Thorn, in press) was developed for use with patients with brain injuries in inpatient rehabilitation settings. It was designed to assess orientation to person and personal situation, place, time, schedule, and temporal continuity. Interrater reliability for the TORP was examined with the use of 34 brain-injured and 35 non-brain-injured patients. Two occupational therapists trained in administering the TORP, as specified in the test manual (Dietz et al., in press), served as the examiners. One therapist administered and scored the test while the second therapist observed and scored the test for the same subject. Intraclass correlation coefficients, used as indexes of reliability for the scoring of the total test and subtests, ranged from .89 to 1.00 for the non-brain-injured group and from .94 to .99 for the brain-injured group. These findings suggest that an occupational therapist can reliably score the TORP for patients both with and without brain injuries. PMID- 2220997 TI - The value of psychosocial Level II fieldwork. AB - The shortage of occupational therapists choosing to practice in mental health and the increase of therapists electing to specialize in other areas led to a pilot study designed to gather information regarding the value of psychosocial Level II fieldwork. A survey was mailed to 152 practicing occupational therapists who had graduated from Colorado State University in Fort Collins between 1983 and 1988; of the surveys returned, 116 were used in this study. The results indicate that the psychosocial Level II fieldwork experience provides therapists with valuable training and experience regardless of their current area of practice or specialization. The results also suggest that to preserve the holistic approach that occupational therapists offer their clients, psychosocial Level II fieldwork must remain a requirement of occupational therapy programs. PMID- 2220998 TI - The use of relaxation training to enhance functional outcomes in adults with traumatic head injuries. AB - Impaired anxiety management and poor emotional control have a negative effect on the adaptive functioning of persons with head injuries who are in the postacute stages of recovery. This paper outlines a relaxation training program administered individually to 4 adults with severe head injuries. Each subject was in the postacute phase of recovery and had reported stress to be a persistent problem in daily living. The relaxation training protocol combined biofeedback, imagery, autogenic training, and deep breathing. Significant improvement in function, measured by scores on a scale of illness-related dysfunction, support the potential benefits of stress management training as part of functional training programs for persons with traumatic head injuries. PMID- 2221000 TI - Occupational therapy in acute inpatient psychiatry: an activities health approach. AB - This article discusses some of the challenges that occupational therapists working in acute psychiatric inpatient settings commonly face. There is often a lack of sufficient time available for treatment as well as limitations inherent in addressing functional problems in the artificiality of a hospital environment. A theoretical framework is introduced from which the role of occupational therapy and realistic objectives for acute short-term care can be identified. This framework for inpatient occupational therapy practice is based on the concept of activities health, which provides a definition of health in functional rather than medical terms. The importance of emphasizing the patient's competence in roles assumed in community living is emphasized. A step-by-step approach to program development with specific examples is also provided. PMID- 2220999 TI - Developing a variable budget for occupational therapy contract work. AB - Contract occupational therapists need to develop a financial plan for improved control of their business. The variable budget allows financial planning according to actual performance volume. This paper describes a step-by-step method for the development of a variable budget through the illustration of a case example. PMID- 2221002 TI - Program evaluation for accreditation. AB - Program evaluation in preparation for accreditation provides opportunities for the identification of program strengths, weaknesses, and improvement potential. In the present study, naturalistic inquiry, an evaluation methodology responsive to the concerns of persons with a stake in the program, was successfully used in preparation for the accreditation of an occupational therapy program. The experiences of undergraduate students who implemented the program evaluation as part of an honors elective course describe the process, outcomes, benefits, and problems associated with the use of naturalistic inquiry as a responsive program evaluation. PMID- 2221001 TI - Creating excellence in patient care. AB - Occupational therapists are working in health care organizations that operate from an efficiency perspective. There is growing criticism that this approach can put quality patient care at risk. This article proposes the excellence perspective as a way to address quality as well as productivity. The excellence perspective is one that occupational therapists can use as a guide to program innovation. It is a perspective that fits with the occupational therapist's concern for quality patient care and the administration's concern for productivity. This article examines the excellence perspective and describes its use in business and its potential for health care. A case study that exemplifies excellence in patient care is presented. PMID- 2221003 TI - Clinical teaching: fieldwork supervisors' attitudes and values. AB - The purpose of this study was to initiate the identification of fieldwork supervisors' educational needs by ascertaining their values and attitudes toward exemplary principles of teaching advocated by adult educators. Each principle was rephrased as an attitude or value associated with Level II fieldwork, matched with a Likert-type 5-point interval scale, and distributed to a convenience sample of 81 fieldwork supervisors. Ninety-two percent of the questionnaires were returned. The statement responses were tallied by frequency and were then summed and ranked. The range of scores indicated that the fieldwork supervisors' values and attitudes were congruent with the identified principles of teaching. The rankings revealed that the supervisors placed the highest value on providing a thorough orientation and the lowest values on individualization of the fieldwork experience and supervisor-student collaboration. The findings indicate a need for further education about ways to individualize learning and involve students in planning, implementing, and evaluating the learning experience. PMID- 2221004 TI - Upper extremity casting: adjunct treatment for a child with cerebral palsy hemiplegia. AB - A common upper extremity deformity with hemiplegia is pronation contracture of the forearm in association with flexion contracture of the elbow. Early management of the child with hemiplegic cerebral palsy is critical in optimizing overall function. The use of inhibitory upper extremity casting can enhance function and improve arm-hand position. The present paper describes the evaluation process before casting, the goals of each phase of the casting program, and the follow-up. PMID- 2221005 TI - Progressive student expectations based on AOTA's fieldwork evaluation. AB - Behavioral statements for each item of the FWE were developed according to a developmental learning hierarchy and then organized into specific categories and time frames. The performance expectations are presented to occupational therapy students in Level II fieldwork in the areas of psychiatry and physical disabilities; a similar process was used to develop performance expectations for the Level II fieldwork of those studying to be occupational therapy assistants. The advantages of this system over the system we had used previously were readily apparent: Supervisor preparation time was considerably reduced, and the content and format of the supervisory meetings changed. Meetings are now spent productively discussing strengths and patterns of behaviors, rather than reviewing endless lists of behavioral statements. PMID- 2221006 TI - Referral for profit (white paper). American Occupational Therapy Association (AOTA). PMID- 2221007 TI - More on the Barthel Index. PMID- 2221008 TI - Protease nexin-1. Localization in the human brain suggests a protective role against extravasated serine proteases. AB - Protease nexin-1 (PN-1) is a potent thrombin inhibitor that is identical to the glia-derived neurite-promoting factor or glia-derived nexin. Here we report immunocytochemical studies of adult human cerebral cortex that revealed the presence of strong immunoreactivity for PN-1 in capillaries and in the smooth muscle cells of arteries and arterioles. Expression of PN-1 was also abundant in astroglial processes in the parenchyma and in perivascular astroglial endfeet of human cerebral cortex. In situ hybridization with an 35S-labeled RNA antisense probe for PN-1 resulted in significant labeling of astrocytes and blood vessels. Because thrombin is known to cause retraction of neurites and modification of astrocytic morphology at low concentrations, PN-1 around blood vessels may play a major protective role against extravasation of thrombin and possibly other serine protease into the human brain. PMID- 2221009 TI - Megakaryocyte synthesis is the source of epidermal growth factor in human platelets. AB - Epidermal growth factor (EGF) is known to be present in the alpha granules of human platelets; however the source of this EGF, ie, whether it is taken up by the platelets from the circulation, or whether it is packaged into the platelets from the megakaryocyte during thrombopoiesis, is unknown. To determine whether EGF is taken up by platelets, platelets for EGF receptors were assayed and it was attempted to detect uptake of EGF by the platelets from culture medium. Platelets were found to lack EGF receptors, and no uptake of EGF from the culture medium was detected. To assess whether EGF is packaged into platelets from the megakaryocyte, megakaryocytes in frozen section bone marrow cores were stained for EGF protein by immunohistochemistry, and it was demonstrated that EGF is present in megakaryocytes. In addition, staining of megakaryocytes by in situ hybridization for EGF mRNA demonstrated its presence in these cells. Therefore it is concluded that the source of EGF in human platelets is the megakaryocyte and that this EGF is synthesized in the megakaryocyte rather than being taken up from its environment. PMID- 2221010 TI - Early proto-oncogene expression in rat aortic smooth muscle cells following endothelial removal. AB - To study the mechanism(s) of vascular smooth muscle cell proliferation in vivo, mRNA levels of c-fos, c-jun, and c-myc were determined by Northern blot analysis following vascular balloon de-endothelialization (BDE). Medial smooth muscle cells (SMC) were separated and studied by enzymatic digestion of the vessel wall. mRNA levels of c-fos and c-jun from aortic smooth muscle cells (SMC) were simultaneously induced within 30 minutes of BDE and declined to baseline by 1.5 hours, c-myc mRNA did not begin to increase until 1 hour after vascular injury. Levels of c-myc peaked at 2 hours and were sustained for an additional 4 hours before gradually declining. Smooth muscle cells derived from enzyme-treated control aortae that did not undergo BDE expressed c-fos and c-jun, but showed no evidence of c-myc message. In contrast, nonenzymatically treated, non-BDE whole aortae (containing both media and adventitia) demonstrated a prominent c-myc signal, but failed to express c-fos and c-jun. Corresponding examination of adventitia derived from enzyme-treated aortae showed this tissue to be a source of all three proto-oncogenes. The results of this study demonstrate the earliest in vivo molecular markers of vascular injury reported to date and implicate SMC proto-oncogene expression in the initiation of SMC proliferation. Furthermore these findings suggest two avenues for proto-oncogene induction, that are due to (1) vessel wall manipulation and (2) humoral stimulation. PMID- 2221011 TI - Immunopathology of diabetes in the RT6-depleted diabetes-resistant BB/Wor rat. AB - Insulin-dependent diabetes mellitus appears to be an autoimmune disease that is characterized morphologically by insulitis, an inflammation of the pancreatic islets of Langerhans that results in the destruction of the insulin-producing beta cells. The RT6-depleted DR rat provides a good model for the in situ study of insulitis. The authors used the anti-RT6.1 monoclonal antibody to selectively deplete RT6 T cells in DR rats and produce a synchronous and rapid development of insulitis that commences 10 days after treatment. The phenotype of cells that infiltrated the islets at different stages of insulitis in the RT6-depleted DR rat was determined by immunocytochemical techniques. A prodromal period of 10 days was present in which the authors could not detect morphologic alterations within the pancreas. This is followed by a second phase of early insulitis in which a few islets are infiltrated by macrophages and T cells. This rapidly progresses by 18 days to the final phase of generalized insulitis in which the islets are massively infiltrated by macrophages and T cells. PMID- 2221012 TI - Reversal of colchicine-induced mitotic arrest in Chinese hamster cells with a colchicine-specific monoclonal antibody. AB - The ability of a high-affinity colchicine-binding monoclonal antibody to reverse the effects of colchicine on Chinese hamster ovary cells was investigated. Using flow cytometry, a complete mitotic blockade was demonstrated after 16 hours with 2.5 x 10(-7) mol/l (molar) colchicine. Colchicine-induced changes were reversible when equimolar antibody was added simultaneously with or up to 6 hours after colchicine. With further delay in addition of antibody, a progressive irreversible increase in mitotic blockade and increase in mean cell size was observed. Prolonged colchicine exposure, without antibody reversal, led to polyploidy and structural chromosome breakage. Early antibody reversal restored cells to the diploid state, whereas delayed reversal resulted in a time-dependent increase in polyploidy. Colchicine-induced polyploidy and chromosomal aberrations may be the basis for both colchicine toxicity and the time-dependent increase in irreversibility of colchicine effects. PMID- 2221013 TI - Immunohistochemical study of fibronectin in experimental myocardial infarction. AB - Light microscopic immunohistochemical studies were performed to evaluate the distribution of fibronectin in paraffin sections of p-formaldehyde-fixed normal rat hearts and the hearts of rats that had undergone ligation of the left coronary artery. A peroxidase-labeled antibody technique was used, together with appropriate immunohistochemical control procedures, for the localization of fibronectin in normal hearts and in the hearts of sham-operated animals. Fibronectin was localized in the interstitial space between myocytes, and beneath arterial, venous, and capillary endothelium. At 4 hours after coronary ligation, fibronectin was localized in a patchy fashion in the cytoplasm and interstitial space of some of the myocytes in the area supplied by the ligated vessel. At 24 hours, there was more intense, homogeneous staining in necrotic myocytes in the infarcted area and in the capillary endothelium in the border zone. At 48 hours, the intensity of staining for fibronectin was maximal in and between the necrotic myocytes in the center of the infarct and in proliferating and migrating capillaries and fibroblasts in the border zone. Similar patterns of localization were observed at 3 and 7 days after coronary ligation, but with progressive decreases in the intensity of staining. Two sources of fibronectin appeared to have contributed to these changes: plasma fibronectin diffusing through damaged blood vessels would account for the early staining observed in necrotic myocytes in the center of the infarct, whereas de novo synthesis of fibronectin by connective tissue cells and endothelial cells in sprouting capillaries would be responsible for the subsequent staining observed in viable capillaries in the border zone of the infarct. Known properties of fibronectin in vitro, combined with these in vivo observations, indicate that fibronectin may influence the thrombotic, inflammatory, angiogenic, and fibrotic processes involved in infarct healing. PMID- 2221014 TI - Lyme borreliosis in the severe combined immunodeficiency (scid) mouse manifests predominantly in the joints, heart, and liver. AB - The authors describe the histopathologic evolution of Lyme disease in severe combined immunodeficiency (scid) and normal C.B-17 and C57BL/6 mice inoculated with Borrelia burgdorferi. Starting on day 7 after inoculation, all scid mice infected subcutaneously in the tail with a low-passage European tick isolate of B. burgdorferi had clinical evidence of arthritis characterized by reddening and swelling of tibiotarsal joints. Later on, other joints, ie, metatarsal and ulnacarpal joints were also affected. The infection of scid mice resulted in a persistent spirochetemia and the development of a multisystem disease with chronic progressive inflammation of joints, heart, and liver. Major histopathologic alterations included 1) severe joint lesions, characterized by the presence of hyperplastic inflamed synovial lining cells associated with the erosion and destruction of cartilage and/or bone; 2) pancarditis with infiltrations of mononuclear cells in the endocardium, myocardium, and pericardium; and 3) hepatitis with mononuclear cell infiltrations confined to the portal field and central vein, granulomatous reactions, and eventually the development of liver fibrosis. In addition, smaller more confined lesions were found in kidneys, lung, brain, and striated muscle. The inflammatory infiltrates in the various organs were associated mostly with Mac-1+ cells, largely monocytes and macrophages, as well as some polymorphonuclear leukocytes, but not B and T lymphocytes. Infective spirochetes could be readily isolated from blood and joints and were found at the site of inoculum and the myocardium. In contrast, subcutaneous inoculation of normal C.B-17 or C57BL/6 mice with spirochetes in general did not result in clinical signs of arthritis. Only 10% to 20% of the C57BL/6 mice, but none of the C.B-17 mice, showed clinical evidence of oligoarthritis, which appeared not before day 36 after inoculation. In general, the infection of normal mice resulted in minimal lesions in various organs, and no spirochetes could be visualized or reisolated from their tissues. The data demonstrate that Lyme borreliosis may develop in mice in the absence of detectable specific B and T cells and thus suggest an immunologic control of the disease in this species. The scid mouse model therefore can be used to define the components of the immune system responsible for the suppression and/or the progression of the disease. PMID- 2221015 TI - Cell density governs the ability of human bronchial epithelial cells to recognize serum and transforming growth factor beta-1 as squamous differentiation-inducing agents. AB - Sparse (75 to 2000 cells/cm2) density cultures of normal human bronchial epithelial cells uniformly undergo terminal squamous differentiation when incubated in medium containing serum (fetal bovine serum [FBS]) or transforming growth factor beta-1 (TGF-beta 1). It was found that the cell density of the culture affects the probability that a cell will respond to these differentiation inducing agents. Thus whereas irreversible inhibition of DNA synthesis occurs in sparse cell-density cultures within 24 hours after exposure, only a transient (less than 36 hours) depression in DNA synthesis was seen in high (more than 10,000 cells/cm2) density cultures. In addition, although phase microscopic image analysis revealed that virtually all of the cells displayed a squamous morphology within 1 hour after exposure to FBS or TGF-beta 1, observations made 48 to 72 hours later showed the presence of clusters of small prolate spheroid-shaped cells surrounded by many involucrin-positive squamous-appearing cells. Only the small cells were capable of DNA synthesis and cell division as determined by autoradiography and time-lapse photomicrographic images. These replicating cells immediately undergo squamous differentiation if they are subcultured and reinoculated at low cell density and incubated in medium supplemented with FBS or TGF-beta 1. Therefore the probability that a human bronchial epithelial cell will be refractive to FBS- or TGF-beta 1 induced terminal squamous differentiation is solely a function of the cell density of the culture. PMID- 2221016 TI - Decreased expression of integrin adhesive protein receptors in adenocarcinoma of the breast. AB - The integrin superfamily represents a major class of receptors mediating cell substrate adhesion. Our recent study of the tissue distribution of the alpha 2 beta 1 integrin, a cell-surface collagen receptor, revealed that high levels of receptor expression were associated with orderly, regulated epithelial cell proliferation. Those observations prompted the present investigation of alpha 2 beta 1 and other integrins in adenocarcinoma of the breast. The alpha 2 beta 1 integrin was highly expressed on the epithelium of the ducts and ductules of normal breast tissue. Normal or nearly normal levels of the receptor were expressed in fibroadenomas. In contrast, markedly decreased or undetectable alpha 2 beta 1 expression was typical of poorly differentiated adenocarcinomas. Well differentiated lesions exhibited intermediate levels of expression. Similar, but less extensive, decreases in expression were observed for the alpha 5 beta 1 (fibronectin receptor) and alpha v beta 3 (vitronectin receptor). Significant expression of the beta 1 subunit on even poorly differentiated tumors suggests that the expression of other undefined members of the beta 1 family is not reduced to the same low level as alpha 2 beta 1 and alpha 5 beta 1. Expression of the alpha 2 beta 1 integrin was highly correlated with estrogen-receptor expression. Decreased expression of alpha 2 beta 1 and other integrin adhesive protein receptors probably contributes to the altered adhesive properties of tumor cells characteristic of the malignant phenotype. PMID- 2221017 TI - Intraluminal fibrosis induced unilaterally by lobar instillation of CdCl2 into the rat lung. AB - Lung injury induced by intratracheal instillation of cadmium chloride (CdCl2) into the rat lung may serve as a model of human interstitial lung disease. In this study, CdCl2 solutions were instilled through a lobar bronchus into the left lung of the rat. Two doses (400 micrograms or 50 micrograms of CdCl2, each in 400 microliters of neutral saline) were used and the morphologic changes occurring during the first 7 days after a single exposure were documented by light and electron microscopy. With the higher dose, inflammatory cells appeared in the alveolar interstitium 1 day after CdCl2 administration. Edema and thickening of the alveolar walls were evident, as were damaged type I epithelial cells and denuded basement membranes. Fibrin was found in the air spaces. Within 2 days, inflammatory cells were seen in large numbers and fibroblasts were observed passing through gaps in the alveolar basement membranes into the air spaces. By 4 and 7 days after CdCl2, various forms of intraluminal fibrosis, including intrabronchiolar budding, mural incorporation, and obliterative changes, were observed. The contralateral lungs had normal-appearing architecture for all the time points investigated. In the lower dose exposure, gradients of alveolar damage were observed in which normal lung, interstitial fibrosis, and/or intraluminal fibrosis were seen within treated lungs. In the mildly damaged regions, interstitial fibrosis predominated, while in the more severely damaged regions, mural incorporation of the convoluted basement membranes was observed. The pulmonary fibrosis that developed appeared to be similar to some human interstitial lung diseases and may offer a system in which to study the regulation of collagen deposition and fibrosis development in these pathologic conditions. PMID- 2221019 TI - Morphometric analysis of follicular center cell lymphomas. AB - The Lukes/Collins classification of non-Hodgkin's lymphomas subdivides follicular center cell (FCC) lymphomas into four categories based on nuclear size, shape, and state of transformation. Because of the well-recognized difficulty in making these subdivisions in routine histologic sections, a morphometric analysis of typical small cleaved (SC), large cleaved (LC), small noncleaved (SNC), and large noncleaved (LNC) FCCs was performed to describe and compare these four categories using objective parameters. The following features, which had been previously tested on normal follicles, were measured and calculated: nuclear area (NA), nuclear contour index of ellipticity (NCIe), nuclear contour index of nuclear irregularity (NCIni), and a relative chromatin dispersal index (CDI). The presence of nucleoli also was recorded. Mean values for the NA, NCIe, NCIni, and CDI were significantly different among all four FCC lymphoma subtypes, except that the CDI, which reflects transformation, was similar for the SC and LC cell groups. Comparison using the proportion of cells with nucleoli in each case revealed significant differences between all but the SNC and LNC groups. The LC group had the highest mean nuclear ellipticity and nuclear irregularity values. Mean nuclear area was smallest for the SC group followed by the LC, SNC, and LNC groups. Despite these many differences, all parameters showed a broad spectrum of values when either mean values for individual cases of each FCC subtype or distribution curves for all cells within a certain subtype were compared. This morphometric data demonstrates that the four histologically recognized types of FCC lymphomas are distinctive using a more analytic technique. This study also provides further insight into the differences among them. Evidence of nuclear transformation (nuclear size, chromatin dispersal, and frequent nucleoli) is a more important criterion than nuclear contours in distinguishing LNC from LC lymphomas. Although LC lymphomas have some features intermediate between SC and the noncleaved FCC lymphomas, they more closely resemble SC lymphomas. Finally morphometric analyses such as these provide an objective morphologic foundation for future prospective investigations of transformation-related phenomena; these studies may facilitate comparison of morphologic data with immunophenotype and genotype in non-Hodgkin's lymphomas and comparison of various other B-cell neoplasms with follicular center cell neoplasms. PMID- 2221018 TI - MaxEPA fish oil enhances cholesterol-induced intimal foam cell formation in rabbits. AB - In this study, the cholesterol-fed rabbit model was used to test the hypothesis that fish oil supplementation can influence the initiation and development of atherosclerotic lesions. Rabbits were fed one of two diets for a period of 30 days: a nonatherogenic diet with corn oil as the sole fat source, or an atherogenic diet containing beef tallow and cholesterol. In addition, animals received a daily supplement of either MaxEPA fish oil or corn oil (0.5 ml/kg body weight). Terminal blood samples were drawn and the cholesterol and triglyceride levels determined for both plasma and very low-density (VLDL), intermediate density (IDL), low-density (LDL), and high-density (HDL) lipoproteins. Thiobarbituric acid-reacting substance (TBARS), an indicator of lipid peroxidation, was measured in the plasma samples. Besides these biochemical parameters of atherogenesis, the number of intimal foam cells in the descending thoracic aorta of each animal was determined by microscopic examination of the vessels en face. In rabbits fed the nonatherogenic diet, fish oil supplementation did not significantly affect any of the biochemical parameters that were measured. In contrast, fish oil supplementation of the atherogenic diet led to a significant increase in the LDL- and HDL-cholesterol as well as the HDL triglyceride levels. Plasma TBARS also increased more than four times. Morphologic analysis of the vessels from rabbits fed the atherogenic diet indicated that fish oil supplementation led to a threefold increase in the number of intimal foam cells, a result that may be linked to increases in both LDL cholesterol and plasma TBARS. The results of these experiments do not support the hypothesis that dietary fish oil will inhibit the initiation or progression of lesion formation in the cholesterol-fed rabbit. PMID- 2221020 TI - Perturbation of differentiated functions during viral infection in vivo. In vivo relationship of host genes and lymphocytic choriomeningitis virus to growth hormone deficiency. AB - Retarded growth and disordered glucose metabolism secondary to growth hormone (GH) deficiency are associated with persistent lymphocytic choriomeningitis virus (LCMV) infection of GH-producing cells in the anterior lobe of the pituitary gland. Infected C3H/ST mice, which are H-2k haplotype, become GH deficient, and LCMV replicates in most (more than 90%) of their GH-producing cells. In contrast, BALB/WEHI and SWR/J mice, which are H-2d and H-2q, respectively, do not develop this GH deficiency, and less than 20% of their GH-producing cells are infected by virus. Yet all three strains infected at birth with LCMV strain Armstrong (ARM) carry equivalent amounts of virus in their blood, brain, heart, kidney, liver, spleen, and thymus throughout life. Of five additional H-2k murine strains tested, C3H/HEJ and CBA/N mice develop this GH-like disorder, whereas neither AKR/J, B10/BR, nor BALB/KAE mice do, indicating that the H-2K haplotype does not control the GH susceptibility. Furthermore C3H/SW mice, which have the H-2b haplotype on the C3H background, develop the disease, again negating any correlation with H-2k but inferring that the C3H background is responsible. One half of the hybrid offspring produced by crossing the C3H/ST GH-deficient strain with BALB/WEHI-resistant mice develop the disease, but the trait is not sex linked. F1 hybrid backcrosses with the susceptible C3H/ST parental strain or resistant BALB/WEHI strain indicate the involvement of more than two genes. Hence the development of a GH deficiency by LCMV-infected C3H/ST mice is not linked to the MHC haplotype, is not sex linked, and is not due to a dominant gene. Multiple genes are involved and these are related to C3H background. PMID- 2221021 TI - Bacterial lipopolysaccharide transforms mesangial into proliferative lupus nephritis without interfering with processing of pathogenic immune complexes in NZB/W mice. AB - Systemic lupus erythematosus is a multifactorial systemic disease in which genetic, immunologic, hormonal, and environmental factors may contribute to disease pathogenesis. Bacterial products (eg, bacterial lipopolysaccharide [LPS]) induce a lupuslike disease in normal mice and trigger an early and accelerated form of lupus nephritis in NZB/W mice. To investigate whether the mechanism by which LPS accelerates nephritis in the NZB/W mice involves interference with processing of immune complexes (IC), we administered LPS to NZB/W mice for 5 weeks and probed the kinetics of removal, liver uptake, and organ localization of a subsaturating dose of radiolabeled IC (2.5 mg of bovine serum albumin antibovine serum albumin). Control NZB/W mice received vehicle (saline) alone. In NZB/W exposed to LPS, features of polyclonal B-cell activation (PBA) were enhanced, anti-DNA antibodies were raised, and a proliferative glomerulonephritis developed that was associated with renal insufficiency and substantial proteinuria. This LPS-accelerated nephritis could not be attributed to altered complement concentration, to altered blood cell carrier function, to delayed removal of pathogenic (large-sized) ICs from the circulation, to impaired liver uptake of ICs, or to enhanced localization of ICs in kidney. The findings indicate that transformation of nephritis is probably the result of LPS-induced PBA, that defective processing of pathogenic IC is not a contributory factor to nephritis, and that mechanisms other than passive renal localization of circulating ICs must be operative. PMID- 2221022 TI - Separate and combined interactions of fibrinogen-gold and latex with surface activated platelets. AB - Glycoprotein (GP)IIb-IIIa receptors on human platelets in suspension and after surface activation bind a variety of specific antibodies and ligands and transport them across the outside of the plasma membrane by processes of clustering, patching and capping, and endocytosis to the platelet interior. The present study evaluated the separate and combined interaction of fibrinogen coupled to colloidal gold (Fgn/Au) and small latex particles with fixed and unfixed, surface-activated platelets. Results demonstrate that populations of GPIIb-IIIa and other mobile receptors on fully spread platelets are not exhausted by binding and transporting a single ligand. Addition of a first ligand followed by a second one results in concentration of the initial wave in the platelet center, surrounded by a halo of second ligand. The margin of the double-labeled cell is cleared of both ligands. However, if the double-labeled platelet is fixed briefly and exposed to a third wave of ligand, that also will bind to the cell and cover the peripheral margin. How many waves of ligand can couple to spread platelets and translocate before the ability of the plasma membrane receptors to bind and clear has been depleted remains to be determined. Yet evidence of the interaction with three waves indicates that the surface-activated platelet has a nearly inexhaustible population of mobile receptors to participate in hemostatic events. PMID- 2221023 TI - Cladistics and the hominid fossil record. AB - Cladistic methodology has become common in phylogenetic analyses of the hominid fossil record. Even though it has correctly placed emphasis on morphology for the primary determination of affinities between groups and on explicit statements regarding traits and methods employed in making phylogenetic assessments, cladistics nonetheless has limitations when applied to the hominid fossil record. These include 1) the uncritical assumption of parsimony, 2) uncertainties in the identification of homoplasies, 3) difficulties in the appropriate delimitation of samples for analysis, 4) failure to account for normal patterns of variation, 5) methodological problems with the appropriate identification of morphological traits involving issues of biological relevance, intercorrelation, primary versus secondary characters, and the use of continuous variables, 6) issues of polarity identification, and 7) problems in hypothesis testing. While cladistics has focused attention on alternative phylogenetic reconstructions in hominid paleontology and on explicit statements regarding their morphological and methodological underpinnings, its biological limitations are too abundant for it to be more than a heuristic device for the preliminary ordering of complex human paleontological and neonatological data. PMID- 2221024 TI - Dermatoglyphic and anthropometric relationships within the Inupiat (Eskimo) hand. AB - On the basis of earlier findings with Easter Islanders suggesting a positive correlation between dermatoglyphic variables and hand anthropometric measurements, the present study was designed to determine if such a relationship could be generalized to another population, namely, Inupiat (Eskimo). Since some dermatoglyphic and anthropometric variables were available for both sides of the body, the extension of this study to explore the question of asymmetry was also possible. The Inupiat sample numbered 142 male and 176 female adult inhabitants of five Alaskan North Slope communities. The major findings of this study included, for males, significant negative correlations between left arm length and digital ridge counts and positive relationships between the palmar variable of axial index and hand length on both hands. For females, the hand breadth/length index was negatively related to most of the digital variables. Very little definitive information regarding the relationship of the asymmetry variables between the two types of measures was ascertained. PMID- 2221025 TI - Size of the sella turcica and its relation to iron deficiency anemia: a prehistoric example. AB - This paper examines the usefulness of volume and area assessments of the sella turcica from radiographs in order to aid in the differential diagnosis of iron deficiency anemia in past populations. Lateral and posterior-anterior radiographs were taken of each cranium in the sample. The length, depth, and width of the sella turcica were then measured directly from the appropriate view, and subsequently the volume and area were calculated for each. The 20-25 year-old cohort was found to yield the most promising results; however, a statistical difference was not found to exist using the volume or area. The width dimension was found to be of far more use than any other in this study. In no instance was any feature of typical porotic hyperostosis, visually or radiographically, found to be statistically correlated with any difference in the dimensions of the sella turcica. A discussion of how the various dimensions of the sella turcica react to changes in size of the hypophysis cerebri is presented. PMID- 2221026 TI - An epidemiologic study of sacroiliac fusion in some human skeletal remains. AB - A case-control study was undertaken to generate some hypotheses concerning the etiology of sacroiliac fusion in a group of skeletons dating from the 18th and 19th centuries. Forty-one skeletons with fusion of the sacroiliac joint were compared with eighty-two adult skeletons without the condition. The sacroiliac joints were most frequently fused with bridging osteophytes and no preference for site or side of fusion could be detected. Except where there were other features in the skeleton suggestive of a sero-negative arthropathy, radiography demonstrated that there was no intra-articular ankylosis. We were able to confirm earlier observations that the condition is more prevalent in males and in older age-groups. The study also showed a significant association between sacroiliac fusion and the presence of diffuse idiopathic skeletal hyperostosis (DISH) and osteoarthritis of the spine but not for osteoarthritis at any other site. There was a highly significant association between sacroiliac fusion and the phenomenon that we refer to as "bone forming." We devised a series of bone-former scores and were able to show a significant excess of cases with high scores compared with the controls. This association persisted when allowance had been made for potential confounding factors such as DISH, osteoarthritis of the spine, and age. PMID- 2221027 TI - Metatarsophalangeal joints of Australopithecus afarensis. AB - Metatarsophalangeal joints from African pongids, modern humans, and Australopithecus afarensis are compared to investigate the anatomical and mechanical changes that accompanied the transition to terrestrial bipedality. Features analyzed include the shape and orientation of the metatarsal heads, excursion of the metatarsophalangeal joints, and orientation of the basal articular surface of the proximal phalanges. These features unequivocally segregate quadrupedal pongids and bipedal hominids and demonstrate a clear adaptation to terrestrial bipedality in the Hadar pedal skeleton. PMID- 2221028 TI - Deconstructing reconstruction: the OH 62 humerofemoral index. AB - The humerus and femur of the fossil hominid OH 62 are badly damaged and their lengths are not directly measurable (Johanson et al., 1987). Nevertheless, using relatively intact reference materials from another early hominid, AL 288-1, Johanson et al. (1987) reconstructed the bones to estimate the humerofemoral index, which falls well above the range for modern Homo, above the estimate for AL 288-1, and within the range for Pan paniscus. The reconstruction of missing bone by the method originally employed for OH 62 is broadly reproducible in a representative modern sample of Homo, making possible the estimation of an associated error term intrinsic to this method. Using the approximate variance of the ratio mean (Kish, 1965), shown here to be a good estimator of the sample variance of the humerofemoral index, the analysis of this modern sample extrapolated to other living hominoids gives quite acceptable results. Applied to OH 62, it suggests an error term associated with the estimated humerofemoral index so substantial that it is only possible to situate the index somewhere between the distributions for Homo and Gorilla, and quite possibly not above the index for AL 288-1. On the other hand, the predicted distribution for the humerofemoral index of AL 288-1 is more securely placed between the distributions for Homo and Pan paniscus. PMID- 2221029 TI - Studies of ancient crania from northern Africa. AB - Historical sources and archaeological data predict significant population variability in mid-Holocene northern Africa. Multivariate analyses of crania demonstrate wide variation but also suggest an indigenous craniometric pattern common to both late dynastic northern Egypt and the coastal Maghreb region. Both tropical African and European metric phenotypes, as well intermediate patterns, are found in mid-Holocene Maghreb sites. Early southern predynastic Egyptian crania show tropical African affinities, displaying craniometric trends that differ notably from the coastal northern African pattern. The various craniofacial patterns discernible in northern Africa are attributable to the agents of microevolution and migration. PMID- 2221030 TI - Three-dimensional computed tomography of the mummy Wenuhotep. AB - Computed tomography allows cross-sectional imaging of anthropological as well as clinical subjects. Recently, technical innovations have made three-dimensional reconstruction of these images feasible. We performed two-dimensional and three dimensional computed tomography of a Late Period Egyptian mummy to reexamine findings seen on previous radiographic studies and to evaluate the usefulness of these techniques in paleopathology. Two-dimensional images provided excellent anatomic detail. There was graphic depiction of the mummification process that corroborated information previously obtained from Egyptological studies. Three dimensional reconstruction provided images of facial features as if the mummy had been unwrapped. Three-dimensional computed tomography is a useful method of nondestructively evaluating paleopathological remains, and it may yield information not obtainable by any other means. PMID- 2221031 TI - Uralic genes in Europe. AB - We have analysed data of three European populations speaking non-Indoeuropean languages: Hungarians, Lapps, and Finns. Principal coordinate analysis shows that Lapps are almost exactly intermediate between people located geographically near the Ural mountains and speaking Uralic languages, and central and northern Europeans. Hungarians and Finns are definitely closer to Europeans. An analysis of genetic admixture between Uralic and European ancestors shows that Lapps are slightly more than 50% European, Hungarians are 87% European, and Finns are 90% European. There is basic agreement between these conclusions and historical data on Hungary. Less is known about Finns and very little about Lapps. PMID- 2221033 TI - Atresia of the external acoustic meatus in prehistoric populations. AB - A case of atresia of the external acoustic meatus is presented from a prehistoric Late Woodland site in Iowa. The affected individual was a female aged 30 to 40 years. The left temporal bone displayed a thin bony plate occluding the external acoustic canal. No evidence of middle ear or inner ear malformation was observed on the axial tomographs, although the external canal was shortened. The individual is diagnosed as having a mild case of congenital atresia. The report extends the geographical and temporal distributions of this archaeologically rare condition. PMID- 2221032 TI - Caries experience in Mediaeval Scots. AB - Dental caries prevalence, distribution, and site of attack was investigated in a Scottish Mediaeval population. The findings supported previous reports, which suggested that caries prevalence in Scotland was lower than in contemporaneous English populations. Attrition of the occlusal surface of the teeth with accompanying alteration of the anatomy of the interproximal space is suggested as the principal reason for the differences in the pattern of distribution of caries between this and modern populations. PMID- 2221034 TI - Paleoepidemiology of a central California prehistoric population from Ca-Ala-329: II. Degenerative disease. AB - Degenerative lesions are scored and frequencies of involvement are computed for a skeletal collection from Ca-Ala-329, a prehistoric site on the southeastern side of San Francisco Bay, dating from 500 A.D. up to European contact. A large earthmound site, excavations conducted there by San Jose State University retrieved close to 300 burials. For this epidemiological analysis, reasonably complete and aged skeletons representing 77 adult females and 90 adult males are available. Degenerative changes are scored macroscopically in an ordinal fashion for the large fibro-cartilagenous joints between adjacent vertebral bodies (vertebral osteophytosis) as well as the small apophyseal articulations of the spine. In addition, in the peripheral skeleton degenerative changes are scored in the temporo-mandibular, shoulder, elbow, hip, and knee joints as well as the small articulations of the hands and feet. The most common degenerative changes in the spine are seen between the vertebral bodies of the lower lumbar region. In the peripheral skeleton the highest involvement of degenerative disease is seen in the hands and feet. Compared to other relevant osteological samples, this group of hunting-gathering California Indians shows more degenerative changes than settled agriculturists (from Pecos Pueblo, New Mexico) but substantially less frequent involvement than in arctic hunters (Alaskan Eskimos). PMID- 2221035 TI - Differences between the hand-wrist and the knee in assigned skeletal ages. AB - Skeletal ages were assessed for 4,902 pairs of hand-wrist and knee radiographs of children aged 2-17 years. The FELS method was used to assess the hand-wrist, and the RWT method was used to assess the knee. These methods have the same conceptual and statistical basis. The mean absolute differences, within age- and sex-specific groups, ranged from 0.34 to 0.87 years. The SD of the differences ranged from 0.31 to 0.68 years and, like the means, tended to increase with age until about 8-11 years. The means and SD were generally larger for the boys than for the girls, except after 14 years. Within age- and sex-specific groups, the maximum absolute differences were from 1.45 to 2.99 years. These maximum differences changed irregularly with age but tended to increase until 11 years in the boys and 9 years in the girls. These large absolute differences between the skeletal ages of the hand-wrist and the knee cannot be explained completely by the effects of observer errors. The means of the relative (signed) differences between the skeletal ages of the hand-wrist and the knee were all close to zero, but there was a wide range within age- and sex-specific groups. These skeletal ages of the hand-wrist and the knee are not interchangeable. The 95th percentiles of the absolute differences show that, in at least 5% of children, the choice of the area for skeletal age assessment will markedly influence the evaluation of individuals. They also demonstrate that descriptions of populations based on distributions of skeletal ages from one part of the skeleton may be misleading. PMID- 2221036 TI - Extracellular magnesium-dependent sodium efflux in squid giant axons. AB - Experiments were designed to determine whether the putative Na(+)-Mg2+ exchanger previously demonstrated to mediate Mg2+ efflux (R. DiPolo and L. Beague. Biochim. Biophys. Acta 946: 424-428, 1988) could also mediate the efflux of Na+ (presumably a Na+ efflux-Mg2+ influx exchange) in squid giant axons. The effects of external Mg2+ (Mg(o)) on 22Na efflux were measured in internally dialyzed, ATP fueled axons in which the contribution to Na+ efflux by other pathways was inhibited. To facilitate measurement of Mg(o)-dependent Na+ efflux, the intracellular concentration of Na+ was increased. To prevent Na(+)-Na+ exchange, external Na+ was replaced by tris(hydroxymethyl)aminomethane. To assess the effect of Mg(o) on Na+ efflux without altering the total divalent cation concentrations, Mg(o) was replaced mole-for-mole by external Ba2+ (Ba(o)). This manipulation produced reversible reductions in Na+ efflux. These reductions were neither due to membrane hyperpolarization nor to a direct effect of Bao but were due instead to the reduction in Mg(o). The Mg(o)-dependent Na+ efflux was inhibited by external amiloride but was spared by bumetanide. In the absence of external Na+, the Mgo-dependent Na+ efflux increased as a function of external Mg2+ with Michaelis-Menten kinetics. These results indicate that the Na(+)-Mg2+ exchange can mediate the efflux of Na+ (operate in Na+ efflux-Mg2+ influx mode of exchange). PMID- 2221037 TI - Regulation of Na-K-Cl cotransport in cultured canine airway epithelia: a [3H]bumetanide binding study. AB - We examined [3H]bumetanide binding to membranes isolated from canine tracheal and bronchial epithelia and to confluent primary cultures of these cells. Crude plasma membranes from trachea and bronchus bind [3H]bumetanide in a saturable manner; tracheal membranes have a higher affinity but lower maximal binding (K1/2 approximately equal to 0.7 microM; Bmax approximately equal to 2.5 pmol/mg protein) than do bronchial membranes (K1/2 approximately equal to 3.5 microM; B(max) approximately equal to 7.5 pmol/mg). In both cases, saturable binding is reduced by greater than 65% when either Na, K, or Cl is removed from the medium. In primary cultures, saturable [3H]bumetanide binding (inhibited by a 30-fold excess of unlabeled bumetanide) occurs when [3H]bumetanide (1.0 microM) is added to the solution bathing the basolateral side of tracheal (1.20 +/- 0.10 pmol bound/mg total cell protein) and bronchial (1.79 +/- 0.52 pmol/mg) cultures; minimal binding is seen with apical [3H]bumetanide. Isoproterenol (10(-5) M; basolateral exposure) produces approximately 100% increase in saturable basolateral [3H]bumetanide binding to tracheal cultures and approximately 30% increase in bronchial cultures. Similar augmentation of binding is seen when apical Cl is reduced from 134 to 4 mM and when both apical and basolateral media are made hypertonic by addition of 100 mM sucrose. Under these latter two conditions, isoproterenol produces little or no additional increase in binding. Our results indicate that the increase in basolateral Cl influx via Na-K-Cl cotransport that must occur during beta-adrenergic stimulation of net salt secretion in canine airway epithelia is related to an actual increase in the number of functioning cotransporters in the basolateral membrane and is not simply due to a change in ion gradients. The increase in cotransport sites, however, may be secondary to initial stimulation of apical Cl channels, with resultant cell shrinkage. PMID- 2221038 TI - Chloride (or bicarbonate)-dependent copper uptake through the anion exchanger in human red blood cells. AB - The initial rate of Cu2+ uptake in human red blood cells was measured by atomic absorption. About 80% of Cu2+ uptake was inhibited by 4,4'-diisothiocyanostilbene 2,2'-disulfonic acid (DIDS) concentrations greater than 5-10 microM. DIDS sensitive Cu2+ uptake required the presence of external HCO3- or external Cl-. Cl strongly stimulated Cu2+ uptake following a Michaelis-like function, with apparent dissociation constant (KCl) of 72 +/- 9.4 (SD) mM (n = 6 experiments). HCO3- stimulated DIDS-sensitive Cu2+ uptake following a Michaelis-like function, with apparent dissociation constant (Kbic) of 10 +/- 1.9 (SD) mM (n = 4 experiments). Maximal rates (of Cl(-)- or HCO3(-)-stimulated Cu2+ uptake) were nonadditive. DIDS-sensitive Cu2+ uptake was not modified by physiological concentrations of phosphate or sulfate. Conversely, it was strongly inhibited by physiological concentrations of L-histidine and cysteine (at a Cu2+ concentration of 100 microM, these physiological ligands exhibited KHis and KCys of 50 and 80 microM, respectively). By using a copper-selective electrode, we found that at pH 7-7.4 copper is associated with OH-, particularly in the form of Cu(OH)2 complexes. In conclusion, the anion exchanger is the major transport mechanism for red blood cell Cu2+ uptake. The translocating species can be the monovalent anion complexes of copper with OH-, Cl-, and/or HCO3-. PMID- 2221039 TI - A factor in serum lowers resistance and opens tight junctions of MDCK cells. AB - During an inflammatory reaction, factors in blood affect the permeability of endothelium and possibly organ epithelium. In this study we partially characterized a factor in human and canine blood that lowered the transepithelial electrical resistance (TER) of canine kidney epithelial cells (MDCK) and examined whether vascular permeability factors [complement component C3a and C5a and platelet-activating factor (PAF)] were responsible for this reaction. C3a and C5a caused a small (10-13%) dose-related decrease in the TER (alpha = 0.05), whereas PAF had no effect. In contrast, the factor found in both serum and plasma caused a large (60-83%) dose-dependent decrease (saturated at 30%) in the TER that was reversible within 60 min. The blood factor, which does not appear to be albumin, was heat stable and has an apparent molecular mass of 67 kDa. It preferentially decreased the TER of the epithelium when it came in contact with its basolateral surface and significantly lowered the resistance within 60 min by opening the zonula occludentes. These findings suggest that C3a, C5a, and a factor in blood can directly modulate the permeability of renal epithelium. PMID- 2221040 TI - Sequence homologies among intestinal and renal Na+/glucose cotransporters. AB - Sodium-dependent glucose transport occurs in the intestine and kidney of most animal species. The cDNA encoding the Na+/glucose cotransporter from rabbit jejunum was used to examine the distribution of homologous mRNA in other rabbit tissues and in the intestines of other species. Northern blots of mRNA extracted from various tissues were probed with radiolabeled cDNA of the cloned rabbit transporter. The probe hybridized with mRNA of approximately 2.2 kb from rabbit jejunum, renal cortex, and renal medulla, indicating that related mRNA of the same size is found in these tissues. With the use of the same cDNA probe, a 1.6 kb partial-length clone encoding 484 amino acids was isolated from a rabbit renal cortex cDNA library. There was greater than 99% identity between the cDNA sequences, and 100% identity between the amino acid sequences, of the renal clone and the rabbit intestinal Na+/glucose cotransporter. The 2.2-kb transcript was seen in mRNA from duodenum, jejunum, and ileum, with a distribution that matched the Na+/glucose transport capacity in these tissues. A faint signal at 2.2 kb was also seen in colon mRNA. There was no detectable hybridization to blots of stomach and heart mRNA. The rabbit probe also hybridized to intestinal mRNA from a number of species from trout to humans. We conclude that a Na+/glucose cotransporter of rabbit renal cortex is very similar to that of the intestine and that the intestinal transporter has been conserved during evolution. PMID- 2221041 TI - Protein kinase C activation and myosin light chain phosphorylation in 32P-labeled arterial smooth muscle. AB - Experiments using 32P-labeled strips of swine carotid artery medial smooth muscle were performed to define the relative contribution of myosin light chain (MLC) phosphorylation as an activation mechanism mediating contractile responses stimulated by phorbol dibutyrate (PDB). Tryptic phosphopeptide mapping of phosphorylated MLC indicated that near-maximal force responses were associated with increases in functional MLC phosphorylation of less than 10% of the total MLC content following tonic (45 min) stimulation by PDB. Significant phosphorylation of MLC residues, consistent with the specificity of protein kinase C, occurred in response to high concentrations of PDB (greater than 0.1 microM). Histamine (10 microM)-induced MLC phosphorylation after 2 min (72.5% of total MLC) or 45 min (61.7%) was restricted to serine residues on peptides thought to contain serine19. Although agonist (histamine)-induced responses were eliminated under conditions of Ca2+ depletion, near-maximal force in response to 10 microM PDB (89.4% of a standard KCl response) was associated with monophosphorylation of less than 9% of the total MLC on peptides interpreted as containing serine19. A substantial fraction of this was localized to threonine residues. The quantitative analysis of the relation between PDB-stimulated force and the residues in MLC phosphorylated supports the concept that PDB stimulation results in activation of arterial smooth muscle cross bridges by MLC phosphorylation-independent mechanisms. PMID- 2221042 TI - Nonmetabolizable glucose analogues and ornithine decarboxylase expression in LLC PK1 cells. AB - This report examines the effect of nonmetabolizable glucose analogues on ornithine decarboxylase (ODC) activity in LLC-PK1 cells. The addition of Na(+) dependent cotransported glucose analogues, 1-O-methyl-alpha-D-glucopyranoside (alpha-MDG) and 1-O-methyl-beta-D-glucopyranoside, to Earle's balanced salt solution minus glucose (EBSS-G) increased ODC activity five- to sevenfold above basal levels. The passive carrier-mediated transported glucose analogue 3-O methyl-D-glucopyranose had very little effect on enzyme activity. alpha-MDG increased ODC activity in quiescent but not growing cells. ODC activity increased as a function of both the incubation time in EBSS-G + alpha-MDG and the concentration of alpha-MDG in EBSS-G. Phlorizin significantly reduced the level of enzyme activity induced by alpha-MDG. ODC expression by alpha-MDG was reduced in cells incubated in hypertonic EBSS-G + alpha-MDG. Enzyme activity, in the absence of extracellular organic substrates, was markedly elevated in cells incubated in hypotonic media. It is suggested that an influx of Na+ and/or an increase in cell volume elevates one or more signal transducers that regulate ODC expression. PMID- 2221043 TI - Hepatic cytochrome P-450 in rats submitted to chronic hypobaric hypoxia. AB - Hepatic cytochrome P-450 content in adaptation to hypobaric hypoxia was studied in three groups of rats and in their respective controls at sea level atmospheric pressure. The experimental groups were as follows: 1) young male and female rats submitted to 4,400 m (simulated altitude) for 6-8 mo, 2) the same animal model of group 1 submitted to 5,500 m (simulated altitude) for a subsequent period of 2-3 mo, and 3) adult males exposed to 5,500 m for 35 days. Hypoxia caused a marked polycythemia in all three groups, body weight loss in males of the three groups and at 5,500 m also in females, whereas liver weight was normal in groups 1 and 2 and slightly decreased in group 3. Cytochrome P-450 content measured in microsomal suspensions of groups 1 and 2 was unchanged. In liver homogenates, cytochrome P-450 content was normal at 4,400 m (group 1) and decreased at 5,500 m (groups 2 and 3). Therefore, endoplasmic reticulum mass, calculated as the ratio of cytochrome P-450 in the homogenates and in the isolated microsomes, was unchanged in group 1 (4,400 m) and decreased in group 2 (5,500 m). The content of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, measured in liver homogenates of group 3, were markedly decreased (by 40, 30, and 35%, respectively). Results do not support the hypothesis that an increase in cytochrome P-450 content plays a role in adaptation to hypoxia. PMID- 2221044 TI - Spatial dynamics of intracellular calcium in agonist-stimulated vascular smooth muscle cells. AB - Vasoconstrictor agonists stimulate smooth muscle contraction by inducing a rise in intracellular free Ca2+. Digital-imaging microscopy of fura-2 fluorescence from single vascular smooth muscle cells cultured from the human internal mammary artery has allowed us to record the subcellular alterations in Ca2+ that occur immediately after stimulation by receptor agonists. The thrombin-induced rise in cytoplasmic free Ca2+ begins in a discrete region typically located close to the end of the cell. Subsequently, this region of elevated Ca2+ expands until Ca2+ is elevated throughout the cell cytoplasm. The rate of spreading in the region of elevated Ca2+ in a linear direction averaged 10.1 microns/s, enabling it to traverse the length of most cells within approximately 5 s, and involved rises in Ca2+ of between 200 and 500 nM. In some cells, the Ca2+ rise began at both ends and collided midway. Similar dynamic changes in the spatial distribution of Ca2+ were recorded in cells stimulated by acetylcholine. The novel observation that vasoconstrictor agonists induce an elevation of Ca2+ in a localized region which subsequently expands throughout the cytoplasm of single smooth muscle cells may provide new insight into the nature of Ca2+ signaling in vascular tissue. PMID- 2221045 TI - Time-varying magnetic fields increase cytosolic free Ca2+ in HL-60 cells. AB - Electromagnetic fields have been reported to cause a variety of biological effects. It has been hypothesized that many of these phenomena are mediated by a primary effect on the concentration of cytosolic free calcium ([Ca2+]i). We investigated the effects of exposure to electromagnetic fields on [Ca2+]i in HL 60 cells using the Ca2(+)-sensitive fluorescent indicator indo-1. Indo-1-loaded cell samples were exposed to a radiofrequency electromagnetic field, a static magnetic field, and a time-varying magnetic field, which were generated by a magnetic resonance imaging (MRI) unit. We found that a 23-min exposure to all three fields, in combination, induced a significant increase in [Ca2+]i of 31 +/- 8 (SE) nM (P less than 0.01, n = 13) from a basal level of 121 +/- 8 nM. Also, cells exposed to only the time-varying magnetic field had a mean [Ca2+]i that was 34 +/- 10 nM (P less than 0.01, n = 11) higher than parallel control samples. Separate exposure to the radio-frequency (6.25 MHz) or static field (0.15 T) had no detectable effects. These results demonstrate that time-varying magnetic fields alter [Ca2+]i and suggest that at least some of the reported biological effects of time-varying magnetic fields may arise from elevation of [Ca2+]i. PMID- 2221046 TI - AVP stimulates adenylyl cyclase and phospholipase C in reciprocal fashion in cultured RIMCT cells. AB - In cultured rat inner medullary collecting tubule (RIMCT) cells, arginine vasopressin (AVP) stimulates adenylyl cyclase (AC) activity in dose-dependent fashion, with no response at concentrations of 10(-10) M or below and with peak activity at 10(-7) M AVP. In contrast, AVP-stimulated phospholipase (PLC) activity is greatest at concentrations at which there is no effect on AC and decreases at higher concentrations of AVP, becoming undetectable at 10(-7) M. Increasing cellular adenosine 3',5'-cyclic monophosphate (cAMP) content with either exogenous ClPheScAMP or forskolin eliminates inositol trisphosphate production in response to 10(-13) M AVP. Conversely, inhibition of AC by 2',5' dideoxyadenosine (DDA) unmasks PLC activity in response to 10(-7) M AVP that is not observed in the absence of DDA. Similarly, DDA prevents inhibition of epidermal growth factor-stimulated PLC by AVP. These findings demonstrate the reciprocal relationship between AVP-stimulated AC and PLC activities in cultured RIMCT cells, which may explain previous divergent results regarding the ability of AVP to stimulate PLC in this tissue. PMID- 2221047 TI - Mechanism of clearance of dipeptides by perfused hindquarters: sarcolemmal hydrolysis of peptides. AB - The objective of the present experiment was to investigate the mechanism of clearance of a load of dipeptides (10 mumols) by perfused hindquarters of rats. The clearance was progressive over 60 min and was significantly (P less than 0.01) greater for glycylleucine than for glycylglycine (99 vs. 58% disappearance from the medium). Insulin had no significant effect on clearance of these dipeptides but stimulated the net uptake of their constituent amino acids. Investigation of the fate of peptides considered resistant to membrane hydrolysis showed a modest (24%) clearance for glycylsarcosine but a substantial one (89%) for glycylproline. Investigation of hydrolysis by sarcolemmal vesicles of skeletal muscle showed hydrolase activity against glycylglycine and glycylleucine but none against glycylsarcosine and glycylproline. Investigation of hydrolysis in the medium previously used to perfuse hindquarters for 60 min showed considerable activity against glycylleucine and glycylproline but none against glycylglycine and glycylsarcosine. These activities were entirely abolished by p hydroxymercuribenzoate, an inhibitor of cytoplasmic peptide hydrolases. In conclusion, our data show that the mechanism of clearance of dipeptides by the perfused hindquarters is largely by hydrolysis, and the site of this hydrolysis differs for different dipeptides; hydrolysis is mediated either by plasma membrane enzymes, cytoplasmic enzymes released into the medium, or a combination of both. PMID- 2221048 TI - Effect of exercise and recovery on muscle protein synthesis in human subjects. AB - Previous studies using indirect means to assess the response of protein metabolism to exercise have led to conflicting conclusions. Therefore, in this study we have measured the rate of muscle protein synthesis in normal volunteers at rest, at the end of 4 h of aerobic exercise (40% maximal O2 consumption), and after 4 h of recovery by determining directly the rate of incorporation of 1,2 [13C]leucine into muscle. The rate of muscle protein breakdown was assessed by 3 methylhistidine (3-MH) excretion, and total urinary nitrogen excretion was also measured. There was an insignificant increase in 3-MH excretion in exercise of 37% and a significant increase (P less than 0.05) of 85% during 4 h of recovery from exercise (0.079 +/- 0.008 vs. 0.147 +/- 0.0338 mumol.kg-1.min-1 for rest and recovery from exercise, respectively). Nonetheless, there was no effect of exercise on total nitrogen excretion. Muscle fractional synthetic rate was not different in the exercise vs. the control group at the end of exercise (0.0417 +/ 0.004 vs. 0.0477 +/- 0.010%/h for exercise vs. control), but there was a significant increase in fractional synthetic rate in the exercise group during the recovery period (0.0821 +/- 0.006 vs. 0.0654 +/- 0.012%/h for exercise vs. control, P less than 0.05). Thus we conclude that although aerobic exercise may stimulate muscle protein breakdown, this does not result in a significant depletion of muscle mass because muscle protein synthesis is stimulated in recovery. PMID- 2221049 TI - Effect of starvation on human muscle protein metabolism and its response to insulin. AB - Although starvation is known to impair insulin-stimulated glucose disposal, whether it also induces resistance to insulin's antiproteolytic action on muscle is unknown. To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using [3H]phenylalanine (Phe) and [14C]leucine (Leu) infused systemically, in eight healthy subjects after 12 (postabsorptive) and 60 h of fasting. After a 150 min basal period, forearm local insulin concentration was selectively raised by approximately 25 muU/ml for 150 min by intra-arterial insulin infusion (0.02 mU.kg-1. min-1). The 60-h fast increased urine nitrogen loss and whole body Leu flux and oxidation (by 50-75%, all P less than 0.02). Post-absorptively, forearm muscle exhibited a net release of Phe and Leu, which increased two- to threefold after the 60-h fast (P less than 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (Ra), with no reduction in rates of disposal (Rd). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P less than 0.01) and completely suppressed the net forearm output of Phe and Leu (P less than 0.02). After the 60 h fast, forearm glucose disposal was depressed basally and showed no response to insulin; in contrast, insulin totally abolished the accelerated net forearm release of Phe and Leu. The action of insulin to reverse the augmented net release of Phe and Leu was mediated exclusively by approximately 40% suppression of Ra (P less than 0.02) rather than a stimulation of Rd. We conclude that in short-term fasted humans 1) muscle amino acid output accelerates due to increased proteolysis rather than reduced protein synthesis, and 2) despite its catabolic state and a marked impairment in insulin-mediated glucose disposal, muscle remains sensitive to insulin's antiproteolytic action. PMID- 2221050 TI - Fetoplacental deamination and decarboxylation of leucine. AB - Fetal and placental metabolism of leucine (Leu) and ketoisocaproic acid (KIC) were studied in seven fetal lambs at 132 +/- 1.3-days gestation. Fetal infusions of [1-13C]Leu, [1-14C]Leu, and antipyrine were carried out for 4 h. Uterine and umbilical blood flows were measured using the antipyrine steady-state diffusion technique. Leu and KIC concentrations, [14C]Leu-specific activities, 14CO2, [13C]Leu, and [13C]KIC enrichment (mole percent enrichment) were measured in the maternal artery, uterine vein, and umbilical artery and vein to calculate net fluxes of tracee and tracer molecules between fetus and placenta and between the uteroplacenta and the maternal circulation. There were net Leu and KIC fluxes into the fetus from the placenta with the KIC flux equal to approximately 19% of the combined Leu plus KIC flux. In addition, there was a net KIC flux into the uterine circulation. The fraction of infused tracer Leu escaping the placenta into the mother was small (approximately 6%). By contrast, there was a rapid exchange of tracer Leu carbon between placenta and fetus resulting in a significant flux of labeled KIC from placenta to fetus. Approximately 20% of the infused tracer carbon was converted to CO2 within the fetus. This rate of conversion was greater than 80% of the total fetoplacental conversion rate and significantly higher than the flux of KIC tracer carbon from placenta to fetus. Fetal KIC decarboxylation rate, calculated from the fetal KIC enrichment data, was 2.83 +/- 0.40 mumol.min-1.kg fetus-1 and approximately 60% of the combined net Leu and KIC flux into the fetus from the placenta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221052 TI - Formation of gluconeogenic precursors in rat skeletal muscle during fasted-refed transition. AB - During the fasted-refed transition, hepatic glycogen repletion from glucose can occur by the direct and indirect pathway. In the indirect pathway, glucose is first metabolized to 3-carbon intermediates that then are converted in the liver to glucose 6-phosphate via the gluconeogenic pathway before conversion to glycogen. The present study evaluated whether skeletal muscle is a major source of 3-carbon intermediates (i.e., lactate, pyruvate, and alanine) during refeeding of 1-day fasted rats. Arteriovenous differences for lactate, pyruvate, and alanine across the anesthetized rat hindlimbs were used to evaluate muscle metabolism in the fed, fasted, and refed state. In the fasted state, liver glycogen was depleted, and muscle released 3-carbon intermediates. One hour after refeeding, hepatic glycogen was 30% repleted, and blood lactate, pyruvate, and alanine increased. Despite this, the release of alanine by muscle diminished at this time and lactate was removed. At 4 h after refeeding, 3-carbon intermediates were all released by hindlimb tissue but in an amount not greater than in the fasted state. Overall, these results suggest that skeletal muscle in the rat is not a major source of 3-carbon precursors for early postprandial hepatic glycogen repletion via the indirect pathway, nor is the rise in 3-carbon intermediates in blood during refeeding caused by their increased output by muscle. PMID- 2221051 TI - Altered hepatic mitochondrial fatty acid oxidation and ketogenesis in endotoxic rats. AB - Rat hepatic mitochondrial function, including oxidative phosphorylation, fatty acid oxidative capacity, kinetic parameters of carnitine palmitoyltransferase I (CPT I), and sensitivity of CPT I to malonyl-CoA inhibition were studied in vitro in isolated mitochondria following Escherichia coli lipopolysaccharide (LPS). The hepatic mitochondrial CPT I in LPS-treated rats showed a lower apparent maximum velocity (Vmax) for palmitoyl-CoA and Ki for malonyl-CoA without changes in apparent Km for palmitoyl-CoA. The rate of oxygen consumption or end-product formation of palmitoyl-L-carnitine and octanoate was not altered, but the rate of CPT I-dependent palmitoyl-CoA (plus L-carnitine) oxidation was reduced by LPS, when acetyl-CoA produced via beta-oxidation was directed toward citrate. When acetyl-CoA was directed to acetoacetate, the oxygen consumption rates of palmitoyl-L-carnitine and palmitoyl-CoA (plus L-carnitine) were decreased by LPS, although mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase activity was not altered. These results indicate that hepatic mitochondria isolated from LPS treated rats show lower ketogenic and long-chain acyl-CoA oxidative capacity than those of fasted controls, and inhibition of ketogenesis is elicited at a site distal to CPT I in addition to reduction in CPT I activity. PMID- 2221053 TI - Insulin binding to individual rat skeletal muscles. AB - Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5 fold range in specific insulin tracer binding, with heart and predominantly slow twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding. PMID- 2221054 TI - Inhibition of intermediary metabolism by amiodarone in dog thyroid slices. AB - Amiodarone, an iodine-containing antiarrhythmic drug, has been reported to interfere with thyroid function and thyroid hormone metabolism. We studied the effects of amiodarone on basal and agonist [thyroid-stimulating hormone (TSH), phorbol ester, or carbachol]-stimulated glucose oxidation, 32PO4 incorporation into phospholipids, and adenosine 3',5'-cyclic monophosphate (cAMP) concentration in dog thyroid slices. Slices were preincubated with amiodarone at 37 degrees C for 1 h before the addition of agonist and the appropriate radioisotope. cAMP stimulation was measured after 20 min, glucose oxidation for 45 min, and 32PO4 incorporation into phospholipids for 2 h. Amiodarone (0.5 mM) had no effect on basal 14CO2 formation or 32PO4 incorporation into phospholipids but significantly inhibited TSH, phorbol ester, and carbachol stimulation of these parameters. It also inhibited cAMP stimulation by TSH. Inhibition of TSH-stimulated [14C]glucose oxidation was also obtained with another iodide-containing compound, iopanoic acid (0.5 mM), but not with iothalamate (up to 10 mM). Inhibition by amiodarone was still present, but to a lesser extent, when it was added at the same time as the agonist. Inhibition of stimulated [14C]glucose oxidation persisted even after the slices were incubated without amiodarone for 6 h. Inhibition by amiodarone, in contrast to that by inorganic iodide, was not prevented by 1 mM methimazole added at the same time as amiodarone. These results indicate that the inhibitory effects of amiodarone on thyroid function are not due to dissociation of iodide from the molecule. PMID- 2221055 TI - Thermogenesis following meal feeding, isoproterenol, and cold in rats with LH lesions. AB - Responses to several thermogenic stimuli were measured in rats maintaining stable but reduced body weights following lateral hypothalamic (LH) lesions. Oxygen consumption was monitored in open-circuit respirometers before and after exposure to cold (16.5 degrees C), intubation of a meal, and isoproterenol injection (40 micrograms/kg 0.75). Observations were made in both warm- (28 degrees C) and cold acclimated (9 degrees C) LH-lesioned rats. Cold exposure, intubation, and drug injection each caused marked increases in heat production in sham- and LH lesioned rats. This thermogenic response was similar in magnitude and form for both groups. Acclimation to 9 degrees C caused increased baseline levels of heat production when measured at 28 degrees C. Subsequent exposure to thermogenic stimuli revealed an exaggerated response to isoproterenol but not intubation in cold-acclimated groups. The LH-lesioned cold-acclimated rats responded in the same manner as sham-lesioned cold-acclimated rats. These findings are in contrast to the immediate postlesion period when rats show enhanced thermogenic activity. At reduced body weights LH-lesioned rats show normal rates of heat production and make normal responses to thermogenic stimuli. Enhanced thermogenesis does not appear to play a role in the maintenance of chronically reduced body mass in LH lesioned rats. PMID- 2221056 TI - Novel effects of insulin secretagogues on capacitation of insulin release and survival of cultured pancreatic islets. AB - Agents that stimulate insulin release from fresh pancreatic islets were tested for their ability to capacitate pancreatic islets to secrete insulin and to support beta-cell survival in tissue culture. Capacitation was defined as the ability to release insulin after 24 h in culture in the presence of an insulinotropic concentration of a secretagogue. Viable islets that lose glucose induced insulin release gradually regain it during culture for 24 h in 20 mM glucose. Survival was defined as the ability to regain glucose-induced insulin release. To measure insulin release after culture, islets were incubated with various secretagogues in Krebs-Ringer buffer for 1 h. Examples of the diverse patterns of responses included the following. Glucose was the only secretagogue that capacitated glucose-induced release. Leucine-, leucine plus glutamine-, and glyceraldehyde-induced release remained capacitated after culture with no secretagogue. Culture at high glucose completely inhibited leucine-induced release. Culture at low glucose (1 mM) or at both high leucine and glutamine abolished glucose-induced release. Only leucine and glutamine capacitated monomethyl succinate-induced release. All agents including subinsulinotropic glucose (1 mM), except D-glyceraldehyde, permitted islet survival. Thus the metabolic pathways for initiation, capacitation, and survival are not identical between and within secretagogues. There is a reciprocal relationship between leucine and glucose with respect to capacitation. Capacitation follows a time course, which suggests that it is regulated by enzyme induction. PMID- 2221058 TI - Acute effects of insulin-like growth factor I and insulin on glucose metabolism in vivo. AB - We have compared the actions of insulin-like growth factor (IGF-I) and insulin on glucose metabolism in vivo, using the glucose clamp technique in rats. Both hormones caused dose-dependent inhibition of hepatic glucose production, stimulation of whole body glucose disposal, and an increase in the glucose metabolic rate of specific muscles. Infusion of IGF-I also decreased the plasma concentration of insulin. An an infusion rate of 0.57 nmol.kg-1.min-1, IGF-I led to stimulation of whole body glucose uptake that was similar to the glucose uptake produced by infusion of 0.01 nmol.kg-1.min-1 insulin. The glucose metabolic rate, as measured by 2-deoxy-D-glucose uptake, was comparable in quadriceps femoris, soleus, and diaphragm muscles during the infusion of 0.57 nmol.kg-1.min-1 IGF-I and 0.01 nmol.kg-1.min-1 insulin. However, at these rates of infusion, IGF-I caused only a 38 +/- 6% inhibition of hepatic glucose output compared with 66 +/- 12% inhibition by insulin (P less than 0.05). Thus, under these conditions, muscle is more responsive than liver to IGF-I, which agrees with the complement of IGF-I receptors in the two tissues. PMID- 2221057 TI - Effects of testosterone on muscle insulin sensitivity and morphology in female rats. AB - Intact or oophorectomized (OVX) female rats were given moderate doses of testosterone for 12 wk. Insulin-stimulated glucose transport with submaximal insulin concentrations was studied with the euglycemic clamp technique. Glycogen synthesis and 2-deoxy-D-glucose uptake were measured during the clamp in the extensor digitorum longus, white and red portions of the gastrocnemius, and in the soleus muscles by tracer technique. Testosterone treatment resulted in elevations of circulating testosterone, increased plasma insulin concentrations, and a marked decrease in insulin-stimulated glucose transport. In control animals, glycogen synthesis and 2-deoxy-D-glucose transport increased with increasing concentrations of type 1 fibers. Testosterone inhibited glycogen synthesis and 2-deoxy-D-glucose transport to approximately 50% in all muscles except 2-deoxy-D-glucose transport in intact rats. Glycogen synthesis in the liver was not affected. Testosterone administration also resulted in changes in muscle morphology. The relative number of type 1 fibers decreased, whereas type 2 fibers increased. This was most pronounced in red muscles. There was also a decrease in capillary density after testosterone treatment. It was concluded that testosterone administered to female rats is followed by marked insulin resistance. This is correlated to alterations in muscle morphology with fewer type 1 fibers and a lower degree of capillarization, which are both known to be characteristics of insulin-insensitive muscles. PMID- 2221060 TI - Oxygen consumption of human adipose tissue. PMID- 2221059 TI - Comparison of in vitro and in vivo 44Ca labeling of bone by scanning ion microprobe. AB - To determine whether Ca incorporation from medium into cultured bone represents normal mineralization, we labeled some neonatal mouse calvariae in vitro and others in vivo with the stable isotope 44Ca and compared surface label localization with a scanning ion microprobe utilizing secondary ion mass spectrometry. To label in vitro, we incubated live calvariae in medium containing 40Ca or 44Ca for 3 h. Compared with a 44Ca/40Ca ratio of 0.020 with 1 mM 40Ca, the ratio with 1 mM 44Ca was 0.135 and with 2 mM 44Ca was 0.556. Erosion revealed a marked decrease in 44Ca/40Ca with depth. To label in vivo, we subcutaneously injected 40Ca or 44Ca into mice equal to a percentage of their total body weight and dissected the calvariae 24 h later. Compared with a 44Ca/40Ca ratio of 0.021 with 2% 40Ca, the ratio with 2% 44Ca was 0.120 and with 6% 44Ca was 0.205. Erosion revealed only a slight decrease in 44Ca/40Ca with depth. Elemental distribution maps of in vivo labeled samples show broad deposition of 44Ca, whereas maps of in vitro labeled bones show 44Ca preferentially localized at the surface in contact with the medium. Thus calvariae can be labeled with 44Ca both in vitro and in vivo. However, the differing patterns of isotope localization under the conditions of this study indicate that in vitro Ca deposition differs from normal in vivo bone mineralization. PMID- 2221061 TI - Validation of tonometric measurement of gut intramural pH during endotoxemia and mesenteric occlusion in pigs. AB - Tonometry is a minimally invasive method for estimating gastrointestinal intramural pH (pHi). Tissue pH is calculated by using the Henderson-Hasselbalch equation and measurements of arterial [HCO-3] and CO2 tension (PCO3) of saline contained in a Silastic balloon within the lumen of the gut. The validity of the method rests on two key assumptions: 1) PCO2 in saline in the tonometer balloon is similar to tissue PCO2 and 2) tissue and arterial [HCO-3] are similar. To validate this method, ileal pHi measured directly with a microelectrode was compared with pHi estimated tonometrically in four groups of anesthetized pigs. Group I (n = 4) were controls. In group II (n = 4), intestinal tissue acidosis was induced by total occlusion of the superior mesenteric artery (SMA). In group III (n = 5), acidosis was induced by partial occlusion of the SMA. In group IV (n = 4), tissue acidosis was induced by endotoxemia. Agreement was excellent between direct and tonometric measurements in groups I and IV and less good in groups II and III. Weighted mean correlation coefficients (rw) for the two measurement methods were 0.743 and 0.9447 in groups II and IV, respectively. Correlation coefficients for the individual animals in group III were more variable than the other groups and ranged from 0.547 to 0.990. The tonometric method for measuring GI pHi is invalid under conditions of zero flow and leads to error under conditions of low flow. However, the method is reliable in the setting of tissue acidosis induced by endotoxemia. PMID- 2221062 TI - Bioavailability of dietary glutathione: effect on plasma concentration. AB - Plasma glutathione (GSH) concentration in rats increased from approximately 15 to 30 microM after administration of GSH either as a liquid bolus (30 mumol) or mixed (2.5-50 mg/g) in AIN-76 semisynthetic diet. GSH concentration was maximal at 90-120 min after GSH administration and remained high for over 3 h. Administration of the amino acid precursors of GSH had little or no effect on plasma GSH values, indicating that GSH catabolism and resynthesis do not account for the increased GSH concentration seen. Inhibition of GSH synthesis and degradation by L-buthionine-[S,R]-sulfoximine and acivicin showed that the increased plasma GSH came mostly from absorption of intact GSH instead of from its metabolism. Plasma protein-bound GSH also increased after GSH administration, with a time course similar to that observed for free plasma GSH. Thus dietary GSH can be absorbed intact and results in a substantial increase in blood plasma GSH. This indicates that oral supplementation may be useful to enhance tissue availability of GSH. PMID- 2221063 TI - Fate of dietary glutathione: disposition in the gastrointestinal tract. AB - Studies were performed in rats that had been fasted 24 h, fed a glutathione (GSH) free semisynthetic diet (AIN-76), and fed the same diet supplemented with GSH. The results from the fasted rats and those fed GSH-free diet showed that the duodenum and jejunum contained 0.2-0.5 mumol of GSH/gram wet wt of luminal contents. The GSH contents of biliary juice was sufficient to maintain this amount of GSH in the intestinal lumen. Other analyses showed that cell sloughing, bacterial GSH content, and GSH secretion by epithelial cells of the jejunum were not sufficient to account for this content. GSH concentrations following consumption of a GSH-supplemented diet (5-50 mg/g AIN-76) showed a rapid increase in all regions of the small intestine and indicated that removal occurred primarily in the jejunum. However, the combined activities of brush-border gamma glutamyltransferase and GSH uptake systems were not sufficient to remove all of the ingested GSH. Results from in situ vascular perfusions of small intestine showed that the upper jejunum is a principal site of GSH absorption. Measurements of the GSH-to-glutathione disulfide (GSSG) ratio in the lumen after ingestion of GSSG (5 mg/g diet) indicated that the upper small intestine also has a mechanism for reducing GSSG to GSH. The results therefore indicate that GSH is present in the lumen of the small intestine of rat under most if not all conditions. Although the physiological importance of luminal GSH remains unclear, it could potentially be used to detoxify reactive electrophiles in the diet or be absorbed for intracellular detoxication reactions. PMID- 2221064 TI - Ontogenetic development of monosaccharide and amino acid transporters in rabbit intestine. AB - We measured brush-border uptakes of seven sugars and amino acids by rabbit intestine as a function of age from the day of birth to adulthood. Gut dimensions, especially those of the colon and cecum, increase more rapidly with body weight than would be true if rabbits maintained identical proportions as they grew. However, nominal small intestinal area increases in approximately direct proportion to the animal's basal metabolic rate. For all solutes except fructose, uptake per milligram of intestinal tissue is maximal at or near birth and declines to a level 2.5-5 times lower in the adult. Because of small intestinal growth, though, the total uptake capacity of the whole length of the small intestine increases in approximately direct proportion to metabolic rate. Fructose uptake per milligram is unique in increasing steeply at the time of weaning, correlated with the post-weaning first appearance of fructose in the natural diet. Age-related changes in uptake ratios among aldohexoses or amino acids suggest developmental sequences of related transporters. Correlated with the very high protein content of rabbit milk, the proline-to-glucose uptake ratio is higher in suckling rabbits than in other sucking mammals. Remarkably, the ratio for adult rabbits is higher than in other monogastric herbivores and is instead similar to values for carnivores. In explanation, although the transport capacity of the small intestine appears to account for proline absorption in rabbits of all ages and for sugar absorption in suckling rabbits, the hindgut may be a major site of carbohydrate digestion in adult rabbits. PMID- 2221065 TI - Dual modulation by adenosine of gastrin release from canine G-cells in primary culture. AB - The effects of adenosine on gastrin release were studied in enzymatically dispersed canine antral cells after 24-36 h in primary culture. We found two contrasting actions for adenosine: inhibition of forskolin-stimulated gastrin release and potentiation of bombesin-stimulated gastrin release. These actions appeared to be mediated by A1 and A2 receptors, respectively. Forskolin stimulated gastrin release was reduced by adenosine and the A1-selective agonist N6-(L-2-phenylisopropyl)adenosine (L-PIA) but not by the A2-selective agonist 2 phenylaminoadenosine (CV 1808). This inhibition by adenosine was reversed by the preferential A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) as well as by the nonselective adenosine receptor antagonist 8-phenyltheophylline (8 PT). Incubation of the cells with pertussis toxin (200 ng, 8 h) reversed the inhibition by adenosine. In contrast, bombesin stimulation of gastrin release was potentiated by adenosine and CV 1808 but not altered by L-PIA. This effect was enhanced by DPCPX and was not altered by treatment of cells with pertussis toxin. In the absence of exogenous adenosine, 8-PT and DPCPX produced a small increase in basal and stimulated gastrin release. These data suggest dual modulation by adenosine of G-cell function. A1 receptors inhibit adenosine 3,5'-cyclic monophosphate (cAMP)-mediated gastrin release via a pertussis toxin-sensitive mechanism, whereas A2 receptors potentiated the response to cAMP-independent stimuli of gastrin release. Enhancement of gastrin release by adenosine antagonists suggests functional restraint by endogenous adenosine. PMID- 2221066 TI - Effect of basolateral acidification on the frog oxynticopeptic cell. AB - The effects of intracellular acidosis induced by acidification of the basolateral (nutrient) perfusate on the structure and function of the oxynticopeptic cell were studied in in vitro frog gastric mucosa. Changing the pH of the unbuffered nutrient perfusate (UNB) from 7.2 to 3.5 acidified the oxynticopeptic cell with no change in potential difference (PD) or resistance (R). Intracellular pH (pHi), PD, and R were 7.05 +/- 0.01, 16 +/- 1 mV, 165 +/- 7 omega.cm2 before and 6.44 +/ 0.01, 16 +/- 2 mV, 170 +/- 9 omega.cm2 after nutrient acidification. Acid secretion (H+) increased from 0.86 +/- 0.07 to 1.88 +/- 0.18 mu eq.cm-2.h-1. Addition of forskolin to tissues perfused with nutrient pH (pHn) 3.5 decreased PD to 2 +/- 2 mV and further increased H+ to 3.07 +/- 0.19 mu eq.cm-2.h-1. By light and electron microscopy oxynticopeptic cells perfused with UNB, pHn 3.5, appeared normal. Oxynticopeptic cells in tissues pretreated with omeprazole and then exposed to UNB, pHn 3.5, had extensive morphological damage. On increasing the pH of the nutrient perfusate from 3.5 to 7.2 there was prompt recovery of pHi in untreated and forskolin-stimulated mucosae (pHi 6.87 +/- 0.06 and 6.85 +/- 0.04) but no recovery of pHi in tissues pretreated with omeprazole or cimetidine (pHi 6.26 +/- 0.04 and 6.44 +/- 0.06, n = 6, 30 min after reexposure to UNB, pHn 7.2). We conclude that in a secreting mucosa intracellular acidification of the oxynticopeptic cell to pHi 6.4 is associated with normal morphology, PD, R, and increased H+, and that intracellular acidosis is not de facto deleterious. PMID- 2221067 TI - Intestinal D-glucose transport and membrane fluidity along crypt-villus axis of streptozocin-induced diabetic rats. AB - Diabetes was induced in male Lewis rats by a single injection of streptozocin (50 mg/kg body wt ip). After 10-14 days, diabetic and age- and sex-matched control animals were killed, and their proximal small intestines were removed. Villus tip, mid-villus, and lower-villus enterocytes were harvested from each group with a method that combined divalent cation chelation with mild mechanical dissociation. These fractions were used as starting material to prepare brush border membrane vesicles. Preparations from each of these fractions were then analyzed and compared with respect to their Na(+)-gradient-dependent and Na(+) independent D-glucose transport, lipid fluidity, and lipid composition. The results of these experiments demonstrated that 1) maximum rates of Na(+)-gradient dependent D-glucose transport (Vmax) were greatest in membrane vesicles prepared from mature cells (villus tip and mid villus) of control rats; 2) the glucose concentration producing half-maximal rates of transport (Km), however, was significantly lower in lower-villus membrane vesicles of control rats, suggesting that a distinct glucose transporter existed in the membranes of these relatively immature enterocytes; 3) Na(+)-gradient-dependent, but not Na(+)-independent, D glucose uptake was greater in diabetic membrane vesicles prepared from mid-villus and lower-villus fractions but not in vesicles prepared from villus-tip cells; and 4) no obvious relationship between alterations in membrane lipid fluidity and enhanced uptake of Na(+)-gradient-dependent D-glucose by these transporter(s) could be established in this experimental model of acute diabetes mellitus. PMID- 2221069 TI - Submucosal plexus alone integrates motor activity and epithelial transport in rat jejunum. AB - It has been well established in several mammalian species, including humans, that contractions of jejunal smooth muscle correlate temporally with increases in mucosal ion transport. Furthermore, this correlation is abolished through local application of neurotoxins, suggesting interaction of enteric neurons. The purpose of this study was to determine whether the myenteric plexus is involved in this correlation. In the rat jejunum in vivo, we simultaneously measured phasic changes in intraluminal pressure and transmural potential difference (PD) as indicators of smooth muscle motor activity and epithelial ion transport, respectively. We compared the temporal association of these parameters in control animals with animals in which either the extrinsic nerves only or the extrinsic nerves and the myenteric plexus of a 5-cm jejunal segment had been ablated 30 days previously. A one-to-one coupling between muscle contractions and transmural PD fluctuations was observed in all animals; ablation of the extrinsic and/or myenteric neurons did not eliminate this correlation. We conclude that, in the rat jejunum, the submucosal plexus alone can integrate the reflex that couples ion secretion to muscle contraction. PMID- 2221068 TI - Ethanol enhances leukocyte-endothelial cell interactions in mesenteric venules. AB - In vivo studies have implicated neutrophils in the gastric mucosal injury produced by intraluminal administration of ethanol. However, in vitro studies indicate that ethanol inhibits various neutrophil functions such as adherence, chemotaxis, and degranulation. The aim of the present study was to assess whether ethanol, at clinically relevant concentrations, is proinflammatory in vivo. Ethanol (0.2, 1.0, 2.0, and 4.0%) was applied to the surface of the cat mesentery, and neutrophil adherence to venules (30 microns diam) and extravasation into the interstitium were quantitated using intravital microscopy. Hemodynamic parameters were also measured (venular diameter, red blood cell velocity, and leukocyte rolling velocity) or calculated (venular blood flow and wall shear stress). In this model ethanol produced a dose-dependent increase in neutrophil adherence and extravasation. The increase in leukocyte-endothelial cell interactions could not be attributed to alterations in hemodynamic factors. Pretreatment of animals with a monoclonal antibody (MoAb IB4) directed to the neutrophil CD11/CD18 adherence complex completely prevented the ethanol-induced neutrophil adherence and extravasation. Pretreatment with a leukotriene B4 (LTB4) receptor antagonist (SC 41930) or a platelet-activating factor (PAF)-receptor antagonist (WEB 2170) did not alter the ethanol-induced neutrophil-endothelial interactions. We conclude that ethanol is proinflammatory at concentrations which may be achieved in the mucosal interstitium during acute alcohol intoxication. The ethanol-induced leukocyte adherence and extravasation is dependent on the expression of adhesive glycoproteins. The inflammatory mediators, PAF and LTB4, do not appear to play an important role in the leukocyte-endothelial cell interactions initiated by ethanol. PMID- 2221070 TI - Hypoxia-induced vasodilation of the feline superior mesenteric artery is not adenosine mediated. AB - The role of adenosine in hypoxia-induced vasodilation was examined in the intestine of pentobarbital sodium-anesthetized cats. A hollow-fiber fetal oxygenator was used to selectively reduce the PO2 of the blood supplying the superior mesenteric artery, thereby inducing hypoxia in the intestines. Decreasing the PO2 from 109 to 38 Torr caused vascular resistance to decrease from 10.2 to 7.5 Torr.kg.min.ml-1, a decrease of 2.7 Torr.kg.min.ml-1 or 24%. During selective adenosine receptor blockade with 8-phenyltheophylline, the same decrease in PO2 (from 109 to 40 Torr) produced a similar decrease in resistance from 5.7 to 3.4 Torr.kg.min.ml-1 or a difference of 2.3 Torr.kg.min.ml-1 (-36%). Thus adenosine is not the mediator of hypoxia-induced vasodilation in the feline intestine because blockade of the vasodilating effects of exogenous and presumably endogenous adenosine did not affect the observed decrease in resistance. PMID- 2221071 TI - Effect of cellular iron concentration on iron uptake by hepatocytes. AB - The effect of intracellular iron content on transferrin and iron uptake by cultured hepatocytes isolated from fetal rat liver was examined with ferric ammonium citrate and the iron chelator desferrioxamine (DFO). Incubation of the cells with ferric ammonium citrate for 24 h significantly increased the cellular nonheme iron level, whereas the number of transferrin binding sites and the uptake of transferrin and iron were reduced. In contrast, when iron-treated cells were incubated with DFO for 24 h, the cellular nonheme iron level was not altered, but the number of transferrin binding sites was increased. Treatment of the cells with exogenous iron and/or DFO did not affect the uptake of transferrin and iron by the nonsaturable processes. These results indicated that, in cultured hepatocytes, transferrin receptor expression and the subsequent uptake of transferrin and iron are regulated by the size of an intracellular, chelatable iron pool, whereas the uptake of iron by the nonsaturable processes is dependent on the extracellular transferrin concentration. PMID- 2221072 TI - Both tissue and serum phospholipases release rat intestinal alkaline phosphatase. AB - Rat intestinal alkaline phosphatase (IAP) is unique among the brush-border membrane enzymes in that it is released bidirectionally (lumen and blood) and exists in either soluble (serum) or particulate (cellular) form. To elucidate the mechanism of membrane release, we examined the effects of phosphatidylinositol specific phospholipase C (PtdIns-PLC) and serum anchor-specific phospholipase D (PLD) on the solubility of the various tissue forms of IAP. The "solubility" of cytosol IAP could be explained in part by intracellular PtdIns-PLC activity, detected by production of acidic IAP isomers, and by ethylene glycol-bis(beta aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)-sensitive PtdIns hydrolysis. Contamination with serum (abundant with anchor-specific PLD) was responsible for the complete or partial solubilization of IAP that was found during processing of light mucosal scrapings. Anchor-specific PLD activity was increased after fat feeding, and the IAP released did not react with antiserum that recognizes the PtdIns-PLC-released phospholipid portion of trypanosomal variable surface glycoprotein. These data are consistent with the hypothesis that, after secretion from the enterocyte bound to a phospholipid-rich membranous particle, IAP release into serum is mediated by serum anchor-specific PLD. The soluble forms of IAP in the lumen and the cytosol fraction appear to be due to a combination of endogenous PtdIns-PLC activity and anchor-specific PLD contamination that occurs during cell fractionation. PMID- 2221073 TI - Role of tyrosine kinases in gastrin induction of ornithine decarboxylase in colonic mucosa. AB - An organ culture system was utilized to evaluate the role of tyrosine kinases (Tyr-k) and tyrosine-specific phosphorylation of proteins in gastrin regulation of ornithine decarboxylase (ODC) activity in colonic mucosa. Exposure of colonic mucosal explants to gastrin (50-100 ng G-17 I/ml) resulted in a profound stimulation of both Tyr-k and ODC activities compared with the corresponding basal levels. Whereas the maximal stimulation (ranging between 70 and 150%) of Tyr-k occurred within 10-15 min of exposure to gastrin, ODC activity was significantly stimulated (180%) 2 h after exposure to the hormone, and at 4 h it was found to be 750% above the corresponding basal level. Difluoromethylornithine (DFMO; 2 mM), an irreversible inhibitor of ODC, completely abolished the gastrin mediated stimulation of ODC but not Tyr-k activity. On the other hand, genistein (100 micrograms/ml), a specific inhibitor of Tyr-k, caused a total suppression of the gastrin-induced stimulation of both Tyr-k and ODC. Gastrin also stimulated tyrosyl phosphorylation of a colonic mucosal membrane protein with molecular mass of 57 kDa, and genistein greatly attenuated this effect. We conclude that gastrin stimulates colonic mucosal ODC in vitro, and Tyr-k may be required for the regulation of this process. PMID- 2221074 TI - Vitamin D-independent intestinal calcium and phosphorus absorption during reproduction. AB - A special metabolic cage system was employed to measure the intestinal, renal, and mammary gland fluxes of Ca, P, and Mg in vitamin D-deficient rats during late pregnancy and lactation. Dietary Ca, P, and Mg levels were 0.78, 0.34, and 0.083%, respectively; this diet minimizes the reduction in milk production observed during vitamin D deficiency. Compared with identically treated virgin rats, lactating rats were slightly hypocalcemic and severely hypophosphatemic. Hypertrophy of the small intestine, as indicated by increased intestinal length and villus height, occurred during lactation. Net fractional intestinal absorption of Ca and P, but not Mg, was elevated twofold during late pregnancy and throughout lactation. Despite this elevated intestinal absorption, lactating rats were in negative Ca and P balance and lost bone mass. The transfer rates of Ca, P, and Mg into milk were approximately 77% of values previously observed in vitamin D-replete rats. Lactating rats conserved P by dramatically reducing renal P excretion. Pup retention of ingested Ca was virtually complete. These results, together with previous observations using everted duodenal gut sacs, indicate that there is a vitamin D-independent stimulation of intestinal Ca and P absorption during pregnancy and lactation. Because fractional Mg absorption was not similarly enhanced, this stimulation shows some specificity. PMID- 2221075 TI - Role of microfilaments in asialoglycoprotein processing in adult and developing liver. AB - To assess the role of microfilaments in receptor-mediated endocytosis of asialoglycoproteins, hepatocytes isolated from adult and 6-day-old rats were treated with the antimicrofilamentous agent cytochalasin D and then incubated with 125I-asialoorosomucoid (ASOR). Cytochalasin D (50 microM) reduced degradation of continuously endocytosed ASOR (7.5 micrograms/ml) equally in adult and neonate to approximately 20% of control. Internalization of surface-bound ASOR suggested at least two discrete sites at which ligand translocation was inhibited by drug at both ages: 1) initial movement of receptor-ligand complex from cell surface to interior and 2) postinternalization ligand transit to lysosomes. Inhibition of plasma membrane translocation was confirmed by calculation of endocytotic rate constant (Ke) values, which were decreased to approximately 20-30% of control after cytochalasin D treatment. In contrast, the antimicrotubular drug colchicine did not reduce Ke values significantly nor did colchicine in combination with cytochalasin D impede lysosome-directed transport more than cytochalasin D alone. These results indicate that internalization of occupied asialoglycoprotein surface receptor is microfilament dependent irrespective of postnatal age and that subsequent participation of microfilaments in asialoglycoprotein trafficking is closely related to that of microtubules. PMID- 2221076 TI - Acidic mucin layer facilitates micelle dissociation and fatty acid diffusion. AB - The presence of a mucin layer on the surface of the intestinal epithelium has been suggested as an important factor in maintaining an acidic microclimate. The presence of such a low-pH compartment has been shown to facilitate fatty acid uptake. The mechanisms leading to the enhancement of fatty acid uptake were investigated in a purified acidic mucin layer. Our results indicate that the presence of a low-pH compartment indeed facilitates the dissociation of mixed micelles made of taurocholate and oleic acid. The released fatty acid formed an emulsion at the mucin layer, and this event could be visualized by the naked eye. When the size of the particles in the micelle solution was examined by photon correlation spectroscopy, it was found that acidification alone can lead to the formation of particles with size substantially greater than that of micelles. With the use of labeled fatty acid, the change in optical density can be correlated to the amount of fatty acid appearing in the mucin layer in an asymptotic fashion, suggesting that using the turbidity as an indicator might underestimate fatty acid diffusion. Despite this limitation, the rate of fatty acid diffusion in the mucin layer was estimated to be 400% of that in the buffer solution. PMID- 2221077 TI - Effect of duodenal amino acid infusion on solid gastric emptying in pigs. AB - The emptying of a 400-g test meal of cubed liver was studied in eight pigs equipped with duodenal cannulas. Gastric effluent was diverted to measure both the rate of emptying and the distribution of particle sizes. The effect of emptying and particle size of infusing normal saline or an isosmolar amino acid solution into the small bowel was studied. Normal saline infusion did not alter the proportion of particles emptied, which were less than 1 mm in diameter. Infusion of the amino acid solution at the same rate significantly decreased the mass of liver emptied from 69.9 to 38.4 g compared with normal saline, and the percentage of particles less than 1 mm in diameter in the gastric effluent increased from 66 to 82%. We conclude that the amino acid solution produced both a reduction in the rate of gastric emptying and an increase in the proportion of small particles in the gastric effluent. We postulate that this may have been due to changes in gastric motility, together with alterations in gastric secretion and digestion, produced by the infusion of the amino acid solution into the small bowel. PMID- 2221078 TI - Lipid binding to gastric mucin: protective effect against oxygen radicals. AB - Gastric mucus forms a viscous gel overlying the gastric mucosa and is thought to protect the underlying mucosa from noxious agents such as acid, proteases, and bile salts. A common property of mucin, the principal glycoprotein in mucous secretions, is its ability to bind lipids. The purpose of this study was to determine if lipids bound to gastric mucin protect the mucin from oxygen radical attack. Pig gastric mucin, partially purified by Sepharose 4B gel chromatography, was found to contain large amounts of free fatty acids and cholesterol as well as lesser amounts of sphingomyelin and phospholipids. Purified mucin obtained by density-gradient ultracentrifugation in a CsCl gradient contained only trace amounts of fatty acids but no other lipids. Exposure to the oxygen radical generating system iron/ascorbate caused a marked reduction in viscosity of purified mucin but did not affect partially purified mucin, suggesting that bound lipids shielded the mucin from attack by oxygen radicals. Using discontinuous sucrose-gradient ultracentrifugation in the presence of liposomes containing [3H]palmitic acid, we demonstrated that mucin is capable of binding fatty acids. We also observed a striking increase in solution viscosity of gastric mucin at low pH, a feature that might contribute to the ability of mucin to form a protective diffusion barrier for the underlying epithelium. PMID- 2221079 TI - Characterization of saturable binding sites for circulating pancreatic polypeptide in rat brain. AB - Pancreatic polypeptide (PP) inhibits pancreatic exocrine secretion by indirect mechanisms that may be centrally mediated. The central site of action of PP that results in inhibition of pancreatic secretion has not been identified. Using autoradiography to identify 125I-PP binding to frozen sections of rat brain, we have identified saturable, high-affinity PP receptors in high concentrations in the interpenduncular nucleus, area postrema (AP), nucleus tractus solitarius, and dorsal motor nucleus of the vagus. The PP receptor differs from neuropeptide Y and peptide YY receptors in its binding specificity and location. Because PP is not produced in the brain, and the blood-brain barrier (BBB) excludes circulating peptides from most areas in the brain, we employed an in vivo radioreceptor assay to determine whether circulating PP binds to areas such as the AP that has both an incomplete BBB and a high concentration of PP receptors. 125I-PP and 131I bovine serum albumin were infused simultaneously into rats through a peripheral vein with or without excess unlabeled PP. After 10 min, rats were killed and the brains were removed and cut into eight regions based on the autoradiographic localization of PP receptors. There was a significant (P less than 0.02) increase in saturable radiolabeled PP accumulation in the region that included the AP, demonstrating that circulating PP can bind to this area of the brain in vivo. PP is released into the circulation after a meal via mechanisms that exhibit vagal and cholinergic dependence. We speculate that PP completes a feedback loop by binding to receptors in the AP and interacting with the adjacent vagal nuclei to inhibit vagal activity. PMID- 2221080 TI - Pathobiology of pulmonary fibrosis. AB - Pulmonary fibrosis is characterized by an increase in lung matrix and alterations in the numbers and spatial relationships of lung parenchymal cells. The increase in matrix results from a proliferation and "activation" of fibroblasts (FB) with increased production and deposition of matrix macromolecules at sites of lung injury. Connective tissue cell activation is associated with increased gene expression of collagens, fibronectin, proteoglycans and other matrix components; cytoskeletal alterations; and probably also with changes in the expression of matrix receptors and matrix-degrading enzymes and inhibitors. The fibroproliferative reaction involves the participation of a variety of cytokines and inflammatory mediators by resident and inflammatory cells at sites of lung injury. Thickening of the alveolar wall can result secondary to matrix deposition within the interstitium and as a result of "mural incorporation" of organized airspace exudate. However, marked structural remodeling of the gas-exchange tissues, with the development of honeycomb lung, involves airspace fibrosis and alveolar collapse. The latter processes lead to areas of airspace obliteration secondary to airspace filling, and to fibrous adhesion of collapsed septa. The extent of airspace obliteration is determined largely by the severity or extent of epithelial injury. Although lung fibrosis is usually irreversible, the activated state is reversible after clearance of exudate and reepithelialization. A continuing and seemingly autonomous fibroproliferative reaction can result in the face of ongoing injury and delayed repair. PMID- 2221081 TI - Strategies for analysis of gene expression: pulmonary surfactant proteins. AB - Gene transcription is regulated by the formation of protein-DNA complexes that influence the rate of specific initiation of transcription by RNA polymerase. Recent experimental advances allowing the identification of cis regulatory sequences that specify the binding of trans acting protein factors have made significant contributions to our understanding of the mechanistic complexities of transcriptional regulation. These methodologies have prompted the use of similar strategies to elucidate transcriptional control mechanisms involved in the tissue specific and developmental regulation of pulmonary surfactant protein gene expression. The purpose of this review is to describe various methodologies by which molecular biologists identify and subsequently assay regions of nucleic acids presumed to be integral in gene regulation at the level of transcription. It is well established that genes encoding surfactant proteins are subject to regulation by hormones, cytokines, and a variety of biologically active reagents. Perhaps future studies utilizing molecular tools outlined in this review will be valuable in identification of DNA sequences and protein factors required for the regulation of lung surfactant genes. PMID- 2221082 TI - Uptake of palmitic acid by rabbit alveolar type II cells. AB - Alveolar type II cells require a source of palmitic acid for synthesis of dipalmitoyl phosphatidylcholine (DPPC), a major constituent of pulmonary surfactant. Previous studies indicated that maximal rates of DPPC synthesis are achieved only if exogenous palmitate is available to the type II cell. Little is known of the mechanisms by which fatty acids enter type II cells. To determine if uptake is mediated by a membrane carrier system, as described in other cell types, we examined the kinetics of palmitate uptake. Using freshly isolated rabbit type II cells, we demonstrated that radiolabeled palmitate uptake was maximal and linear for 45 s; after 1 min the apparent rate of uptake declined. The initial uptake phase was taken as a measure of cellular fatty acid influx because intracellular radiolabeled palmitate remained 80% nonesterified at this time but was 55% esterified by 2 min. Cellular influx of palmitate showed saturation kinetics with increasing concentration of nonalbumin bound palmitate. Michaelis constant was 52.6 nM, and maximum velocity was 152 pmol.10(6) cells 1.min-1. The hypothesis that saturable cellular influx of palmitate is likely linked to the previously identified membrane fatty acid binding protein (MFABP) was supported by Western-blot analysis of rat lung tissue with an antibody to MFABP that demonstrated the presence of this carrier protein in lung tissue. These data suggest that palmitate uptake by type II cells is saturable and may be mediated by a membrane-associated carrier as described in other cell types. PMID- 2221083 TI - Acrolein stimulates eicosanoid release from bovine airway epithelial cells. AB - Injury to the airway mucosa after exposure to environmental irritants is associated with pulmonary inflammation and bronchial hyperresponsiveness. To better understand the relationships between mediator release and airway epithelial cell injury during irritant exposures, we studied the effects of acrolein, a low-molecular-weight aldehyde found in cigarette smoke, on arachidonic acid metabolism in cultured bovine tracheal epithelial cells. Confluent airway epithelial cell monolayers, prelabeled with [3H]arachidonic acid, released significant levels of 3H activity when exposed (20 min) to 100 microM acrolein. [3H]arachidonic acid products were resolved using reverse-phase high-performance liquid chromatography. Under control conditions the released 3H activity coeluted predominantly with the cyclooxygenase product, prostaglandin (PG) E2. After exposure to acrolein, significant "peaks" in 3H activity coeluted with the lipoxygenase products 12-hydroxyeicosatetraenoic acid (HETE) and 15 HETE, as well as with PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. Dose-response relationships for acrolein-induced release of immunoreactive PGF2 alpha and PGE2 from unlabeled epithelial monolayers demonstrated 30 microM acrolein as the threshold dose, with 100 microM acrolein inducing nearly a fivefold increase in both PGF2 alpha and PGE2. Cellular viability after exposure to 100 microM acrolein, determined by released lactate dehydrogenase activity, was not affected until exposure periods were greater than or equal to 2 h. These results implicate the airway epithelial cell as a possible source of eicosanoids after exposure to acrolein. PMID- 2221084 TI - Aldosterone regulation of basolateral potassium channels in alveolar epithelium. AB - To reveal the regulatory mechanism of the mineralocorticoid aldosterone on basolateral K+ channels, the aldosterone-sensitive lung epithelium of Xenopus laevis was investigated in Ussing chambers under voltage-clamp conditions. Transepithelial measurements were supplemented by current fluctuation analysis of short-circuit current noise in nonstimulated and aldosterone-stimulated lung tissues. The addition of 10(-6) M aldosterone stimulated short-circuit current from 11.3 +/- 2.0 to 27.8 +/- 4.8 microA/cm2 (n = 11) within 4-5 h. In the presence of an alveolar-to-pleural K+ gradient, transepithelial K+ currents were induced by permeabilizing the apical membrane with the pore-forming antibiotic amphotericin B. When the local anesthetic lidocaine (25-1,000 microM) was added to the pleural solution, macroscopic K+ current was dose dependently depressed. Lidocaine induced a Lorentzian component in the power density spectra, and the corner frequency increased linearly with blocker concentration. Aldosterone treatment did not affect mean single K+ channel current, which was 1.5 +/- 0.12 pA corresponding to a 15-pS channel conductance, whereas the number of basolateral K+ channels doubled. We conclude that the basolateral K+ channels in alveolar epithelia are a target site of aldosterone action. PMID- 2221085 TI - Uptake of instilled radiolabeled lamellar bodies from alveolar compartment of the rat. AB - Following the instillation of lamellar bodies containing dipalmitoyl phosphatidyl [3H]choline (DPPC) down the trachea of adult rats, we found that the half-life of alveolar [3H]-DPPC was 85 min and the time constant was 120 min. As much as 85% was recycled. When we labeled the DPPC with both [3H]choline and [14C]acetate, the ratio 3H/14C increased in the alveolar compartment and then increased further in the lamellar body fraction of the recipient lungs, suggesting that some deacylation-reacylation was occurring. Further evidence of degradation was an increase in free [3H]choline in the microsomal fraction. Whereas hyperpnea induced by breathing 5% CO2-13% O2-82% N2 increased the reuptake of DPPC, reuptake did not appear to be enhanced in the rest period immediately after hyperpnea induced by swimming, when alveolar DPPC was still markedly elevated. Propranolol did not affect reuptake, suggesting that beta-adrenoreceptors were not essential. We suggest that reuptake is coupled more to release than to the amount of surfactant in the alveolar compartment. PMID- 2221086 TI - Lung fibroblasts from animals breathing 100% oxygen produce growth factors for alveolar type II cells. AB - Type II cells were isolated from rats with a purity of 80-95% with less than 4% macrophages. These cells, after plating for approximately 16 h, were cultured with 50% RPMI 1640 and 50% (vol/vol) conditioned medium obtained from confluent hamster lung fibroblasts, together with 0.1% fetal calf serum (FCS). Conditioned media were obtained from either fibroblasts derived from normal hamsters breathing room air [normoxic-conditioned medium (NCM)] or from hamsters exposed for 4 days to 100% O2 [hyperoxic-conditioned medium (HCM)]. Controls consisted of 100% minimal essential medium (MEM) containing 0.1% FCS. Over a 96-h culture period, NCM stabilized cell populations but was unable to induce proliferation. In contrast, at low cell densities, HCM could cause a two- to threefold increase in type II cell number within 24-48 h after introduction. This effect could not be demonstrated at high cell densities. When tested with FCS concentrations ranging from 0 to 10%, maximum effects were obtained using 0.1-0.2% FCS. We conclude that lung fibroblasts from oxidant-injured hamsters produce growth factors that can stimulate at least one mitotic division in cultured type II cells, which are plated at low density. These factors are absent, or present in much lower concentration, in lung fibroblasts from normal animals. PMID- 2221087 TI - TGF-beta 1 modulation of urokinase and PAI-1 expression in human bronchial epithelial cells. AB - Normal human bronchial epithelial (NHBE) cells respond to signals initiated by the binding of transforming growth factor-beta type 1 (TGF-beta 1) to its surface receptors by activating pathways that result in terminal squamous differentiation. By use of both normal and SV40 T-antigen-immortalized cells, it was found that treatment with TGF-beta 1 transiently increases mRNA levels for urokinase (uPA) and plasminogen activator inhibitor type 1 (PAI-1) approximately 5- and 50-fold, respectively, within 4 h. In NHBE cells, PAI-1 protein is increased by TGF-beta 1 in both extracellular matrix and medium. The net effect of TGF-beta 1 on plasminogen activator activity in the medium was a 50% reduction as measured by a caseinolytic assay. A T-antigen-immortalized bronchial epithelial cell line that does not undergo squamous differentiation in response to TGF-beta 1 but binds this growth factor did not respond to TGF-beta 1 by modulation of either uPA or PAI-1 expression. Comparison of human bronchial epithelial, pleural mesothelial, and lung fibroblastic cell strains indicated that the epithelial cells have a constitutively higher ratio of uPA to PAI-1 mRNA expression. These data suggest that modulation of pericellular proteolysis in bronchial epithelial cells in response to TGF-beta 1 represents a significant biological change in their pericellular environment. The induction of uPA and PAI 1 expression in human bronchial epithelial cells may be related to the ability of the cell to undergo squamous differentiation in response to TGF-beta 1. These observations identify specific changes in gene expression that may serve as markers for the differentiation process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221088 TI - Enzymatic activity is necessary for thrombin-mediated increase in endothelial permeability. AB - alpha-Thrombin causes a dose-dependent increase in endothelial permeability as measured by the clearance rate of 125I-albumin across a monolayer of bovine pulmonary artery endothelial cells. We determined if an active catalytic site is necessary for the thrombin-mediated increase in endothelial permeability. alpha Thrombin was reacted with 10-fold excess D-phenylalanyl-prolyl-arginine chloromethyl ketone (PPACK), an irreversible inhibitor that forms a covalent bond with thrombin's active site, producing an enzymatically inactive thrombin. PPACK completely inhibited the alpha-thrombin-mediated increase in 125I-albumin permeability. Similar results were obtained with gamma-thrombin, an enzymatically active alpha-thrombin form with an altered fibrinogen recognition domain. PPACK alone and the active site-inhibited PPACK-alpha-thrombin had no effect on permeability. Diisopropylphospho (DIP)-alpha-thrombin was effective only in very high concentrations (10(-6)M), and this effect was abolished by the addition of PPACK. These studies demonstrate that binding alone is insufficient for the thrombin-mediated increase in endothelial monolayer permeability. Thrombin's active catalytic site is a requirement for the increase in transendothelial albumin permeability. PMID- 2221089 TI - Epithelium-dependent contraction of airway smooth muscle caused by eosinophil MBP. AB - We have identified two distinct functions of the epithelium of guinea pig airways that modulate airway smooth muscle contractility in the presence of the major basic protein (MBP) of human eosinophilic granules: 1) active force generation resulting less than 1 min after epithelial contact with MBP; and 2) sustained, augmented force generation that does not depend on cytotoxic interference with the synthesis of an epithelial-derived inhibitory factor. To evaluate these influences, an in situ preparation of guinea pig trachea was developed that permitted direct, on-line measurement of isometric force generation in the underlying muscle. Direct application of 10(-8) mol/cm2 MBP to the surface of the epithelium elicited force generation that did not require the presence of a contractile agonist. Force generation began less than 1 min after MBP application and reached maximum active tension (AT) of 0.97 +/- 0.38 g/cm at 30 min (P less than 0.05 vs. baseline). Denatured MBP did not elicit active tension. MBP also caused augmented contraction to intravenous acetylcholine (ACh); 30 min after topical application of MBP, AT generated by 3 x 10(-7) mol/kg iv ACh was 0.85 +/- 0.14 vs. 0.55 +/- 0.08 g/cm in control animals (P less than 0.05). Threshold response to ACh (-8.1 +/- 0.3 log mol/kg) also decreased significantly after MBP (-9.1 +/- 0.4 log mol/kg) vs. baseline (P less than 0.01). Removal of the epithelium (confirmed histologically) abolished both direct contraction and augmented force generation to ACh caused by topical application of MBP to the airway muscle. These data suggest actions of MBP that have not been demonstrated previously: 1) activation of epithelial function that causes direct contraction of airway smooth muscle; and 2) independence of the MBP-induced effects from active tone elicited by other agonists. We also demonstrate that augmented contraction that does not depend on MBP blockade of tonic inhibitory secretion from the epithelium. PMID- 2221091 TI - Glomerular response to hyperglycemia in human diabetic nephropathy. AB - We have studied the effect of acute hyperglycemia on glomerular function in seven insulin-dependent diabetics with overt nephropathy during hyperglycemic or euglycemic clamp. In all patients glomerular filtration rate (GFR) was higher during hyperglycemia than during euglycemia (35.0 +/- 15.5 vs. 21.4 +/- 10.3 ml.min-1.1.73 m-2, P less than 0.01), whereas renal plasma flow did not change significantly. To establish which determinant of GFR is altered by hyperglycemia, fractional clearances of neutral dextrans of graded molecular size were determined in both glycemic states, and data were analyzed by a theoretical model of hindered transport of macromolecules through a porous membrane. Hyperglycemia significantly increased sieving coefficients of small dextran molecules (28-40 A in radius), whereas fractional clearances of large macromolecules (greater than 44 A) did not change. Theoretical analysis suggested that the ultrafiltration coefficient (Kf) and membrane permeability to small dextrans (less than 40 A) increased in hyperglycemia in respect to euglycemia. Because these results have been obtained in patients with severe renal failure and hypertension, our conclusions do not necessarily apply to the early phase of diabetic nephropathy. PMID- 2221090 TI - Endogenous xanthine oxidase-derived O2 metabolites inhibit surfactant metabolism. AB - The ability of xanthine oxidase (XO)-derived, partially reduced O2 species (PROS) to inhibit surfactant production was examined in freshly isolated alveolar type II (ATII) pneumocytes from New Zealand White rabbits. [Methyl-3H]choline chloride and [1-14C]palmitate incorporation into phosphatidylcholine (PC) decreased in a dose-dependent manner, whereas peak media hydrogen peroxide (H2O2) concentration increased, when 1, 5, or 10 mU/ml XO were added to cell suspensions containing 500 microM xanthine. Addition of 100 microM allopurinol inhibited H2O2 production and abolished the decrease in choline and palmitate incorporation into PC. ATII cells incubated with 500 microM xanthine alone incorporated choline and palmitate at 90 and 80% of control levels, respectively. However, 100 microM allopurinol restored precursor incorporation to control values. To identify a possible intracellular source of PROS, ATII cell xanthine dehydrogenase (XDH) and XO activities were measured. Both total activity (XDH + XO; 45 +/- 7 microU/mg protein) and the percentage activity in the oxidase form (%XO; 30 +/- 4%) remained unchanged in ATII cells incubated in media only (control) for 2 h. In contrast, incubation of ATII cells with 500 microM xanthine resulted in a 50% loss of XDH + XO activity and a 21% increase in %XO within 10 min. After 2 h there was no measurable XDH + XO activity in xanthine-treated cells. Total XDH + XO activity in cells incubated with 500 microM xanthine and 100 microM allopurinol was less than 6% of control values throughout the incubation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221092 TI - Segmental distribution of epidermal growth factor binding sites in rabbit nephron. AB - The kidney possesses epidermal growth factor (EGF) receptors and is a major site of synthesis for the EGF precursor, prepro-EGF. To examine the segmental localization of EGF receptors in the rabbit kidney, we characterized 125I-labeled EGF binding to micro-dissected rabbit nephron segments. Specific binding constituted 70-80% of total binding and was saturable with an apparent Kd of 8 nM. Kinetic studies (0 degrees C) revealed an association t1/2 of 20.7 min and a dissociation t1/2 of 27 min. Competition studies revealed that 125I-EGF binding was inhibited by unlabeled EGF or its homologue transforming growth factor-alpha, but not by parathyroid hormone or insulin. Mapping studies showed specific 125I EGF binding (attomoles per centimeter) was highest in proximal straight tubules, followed by proximal convoluted tubules, cortical collecting ducts, inner medullary collecting ducts, outer medullary collecting ducts, and distal convoluted tubules. Specific binding to glomeruli was also observed. Interestingly, no specific binding of 125I-EGF to thick ascending limbs, a site of EGF precursor synthesis, was observed. These studies suggest potential sites of action for EGF in the rabbit kidney. PMID- 2221093 TI - Bilitranslocase localization and function in basolateral plasma membrane of renal proximal tubule in rat. AB - Bilirubin and phthalein dyes are taken up by the liver via a carrier-mediated mechanism operated at least in part by bilitranslocase (BTL). Because they also undergo renal transport, the presence and function of BTL was investigated in rat renal tubular plasma membrane vesicles. Transport of sulfobromophthalein (BSP) was enriched in basolateral domain of plasma membrane and followed the distribution pattern of Na(+)-K(+)-ATPase but not of gamma-glutamyltransferase. BSP uptake was inhibited by addition of monospecific antibodies raised against hepatic BTL. As in liver vesicles, BSP transport was electrogenic, being greatly accelerated by addition of valinomycin in presence of an inwardly directed K+ gradient. Apparent Km of BSP transport was 17 +/- 2 microM (n = 3 expts), one order of magnitude higher than that measured in liver; however, Vmax was similar to that described in liver vesicles (429 +/- 18 nmol BSP.mg protein-1.min-1, n = 3 expts). Competitive inhibition was observed with both unconjugated bilirubin (Ki, 2.9 +/- 0.2 microM) and rifamycin SV (Ki, 76 +/- 10 microM), known competitors for hepatic BTL-mediated transport of BSP. Immunoblotting studies with anti-BTL monospecific antibodies revealed presence of a single positive band only in basolateral-enriched membrane fraction; its apparent molecular mass was 37 kDa, virtually identical to that of hepatic protein. Immunohistochemistry confined presence of BTL to renal proximal tubules (RPT) We conclude that BTL is present in basolateral plasma membrane of RPT cells. Lower affinity of renal, compared with hepatic protein, for substrates might explain the marginal role of kidney in plasma clearance of bilirubin and cholephilic dyes. PMID- 2221094 TI - Restoration of tubuloglomerular feedback in volume-expanded rats by angiotensin II. AB - Experiments were performed in anesthetized rats to examine whether angiotensin II corrects the attenuation of tubuloglomerular feedback (TGF) responses produced by acute extracellular volume expansion. Volume expansion was achieved by an infusion of isotonic saline at a rate of 9 ml/h. When urine flow had stabilized, an increase in loop of Henle flow from 0 to 45 nl/min caused a fall in stop-flow pressure (PSF) by 3.7 +/- 0.3 mmHg and in single-nephron glomerular filtration rate (SNGFR) by 5.1 +/- 1.7 nl/min. During continued saline administration angiotensin II was infused at 16, 48, or 96 ng.kg-1.min-1 while renal arterial pressure was held constant by suprarenal aortic clamping. The mean responses of PSF increased to 5.9 +/- 0.6, 9.8 +/- 0.7, and 14.9 +/- 1.7 mmHg. Angiotensin II infused at 54 ng.kg-1.min-1 increased the SNGFR response to 15.1 +/- 2.1 nl/min, whereas kidney GFR and distal SNGFR fell. Subcapsular pressure was not significantly altered by angiotensin II infusion (16 ng.kg-1.min-1). Plasma angiotensin (y, pg/ml) as a function of angiotensin II infusion rate (x, ng.kg 1.min-1 for approximately 20 min) was found to fit the function y = 2.89 + 3.53x. An infusion of approximately 15 ng.kg-1.min-1 restored plasma angiotensin levels in the volume-expanded rats to hydropenic values. These data confirm that angiotensin II may play a role as a physiological regulator of TGF sensitivity. PMID- 2221095 TI - Renal responses to lower body negative pressure in humans. AB - Renal blood flow, renal sympathetic nerve activity, assessed by the renal overflows of norepinephrine (NE), dopamine (DA), and neuropeptide Y-like immunoreactivity (NPY-LI), as well as plasma renin activity and angiotensin II (ANG II) were evaluated during stepwise increases in lower body negative pressure (LBNP) in 10 healthy volunteers. The fractional extraction of epinephrine (Epi) was used to assess renal catecholamine removal (approximately 50%) from arterial plasma. Renal NE, DA, and NPY-LI overflows at rest were 235 +/- 31, 30 +/- 5, and 0.6 +/- 0.2 pmol/min, respectively. LBNP increased renal vascular resistance (RVR) by 52% and renal NE overflow by 31%. Renin release increased by 330% (from 64 +/- 12 units/min) and arterial ANG II levels by 119%, without altering the renal ANG II extraction (which was approximately 50%). Renal DA and NPY-LI overflows were unaffected. A "vaso-vagal" reaction in one subject was associated with cessation of renal NE overflow and marked elevations of arterial Epi, renal renin release, and arterial ANG II. Selective unloading of cardiopulmonary baroreceptors by low-level LBNP did not affect RVR, whereas higher levels of LBNP caused renal vasoconstriction probably mediated in part by increased renal sympathetic nerve activity and in part by ANG II. PMID- 2221096 TI - Glucose absorption by isolated perfused rat proximal straight tubules. AB - Glucose absorption was investigated in isolated perfused proximal straight tubules from rats by use of a newly developed ultramicrofluorometric assay. This assay takes advantage of the increase in fluorescence associated with the reduction of NAD to NADH while glucose is degraded to 6-phosphogluconate. When tubules were perfused at 6.70 +/- 0.42 nl.mm-1.min-1, the mean rate of glucose absorption was 11.0 +/- 1.0 pmol.mm-1.min-1, and the mean rate of fluid absorption was 0.61 +/- 0.06 nl.mm-1.min-1. Glucose transport is generally due to Na-glucose cotransport in the proximal nephron. In the rat proximal straight tubule, glucose absorption also appeared to be primarily due to Na-glucose cotransport, since 10(-4) M phlorizin inhibited absorption by 100%, as did inhibition of Na(+)-K(+)-ATPase by K removal. To determine the maximum rate of transport, tubules were perfused at rates greater than 20 nl.mm-1.min-1 with a solution containing 5.5 mM glucose. The maximum rate of glucose absorption was approximately 20 pmol.mm-1.min-1 under these conditions. The concentration of glucose that supports 50% of the maximum rate of absorption, Km, was 0.6 mM. When tubules were perfused at flow rates of less than or equal to 2 nl.mm-1.min-1, the luminal glucose concentration reached a limiting value of 0.47 mM with 5.5 mM glucose in the bath. The glucose permeability was 3.1 X 10(-6) cm/s. PMID- 2221097 TI - Pathways for apical and basolateral membrane NH3 and NH4+ movement in rat proximal tubule. AB - To examine the mechanism of preferential luminal ammonia secretion in the proximal tubule the apical and basolateral membrane pathways for NH3 and NH4+ movement were studied in the in vivo microperfused rat proximal tubule. Na and Cl were absent from all perfusates. Changes in pHi in response to rapid addition of NH3-NH4+ to either the luminal or peritubular perfusates were measured microfluorimetrically and expressed as the H(+)-equivalent flux (JeqH in pmol.mm 1.min-1). After ammonia addition ([NH3] 0.3 mM; [NH4+] 14.7 mM) to the luminal or peritubular fluids, pHi increased, and JeqH = 1,713 +/- 181 and 1,040 +/- 132 pmol.mm-1.min-1, respectively. To determine whether the above difference was due to NH3- or NH4(+)-driven fluxes, the effect of a fivefold greater [NH4+] ([NH3] 0.3 mM; [NH4+] 74.5 mM) on JeqH was examined. With luminal addition of a fivefold greater [NH4+], JeqH increased to 3,299 +/- 292 pmol.mm-1.min-1, demonstrating a pathway for NH4(+)-driven H+ efflux. One millimolar luminal amiloride inhibited JeqH in response to luminal NH3-NH4+ addition, suggesting that the amiloride sensitive Na(+)-H+ antiporter mediates the NH4(+)-driven H+ efflux. JeqH was unaffected by addition of a fivefold greater [NH4+] to the peritubular perfusate, demonstrating the absence of an NH4(+)-driven H+ flux on the basolateral membrane. From these data, the calculated NH3 permeabilities were 6.2 +/- 1.3 and 7.0 +/- 0.9 X 10(-2) cm/s for the apical and basolateral membranes, respectively (NS). We conclude that apical and basolateral membrane NH3 permeabilities are similar and large. The apical membrane can also transport NH4+ on the amiloride sensitive Na(+)-H+ antiporter. PMID- 2221098 TI - Relative osmotic effects of raffinose, KCl, and NaCl across basolateral cell membrane. AB - Lumen-collapsed segments of rabbit S2 proximal tubule were bathed in isotonic medium and then exposed acutely to a medium made hypertonic by the addition of raffinose, NaCl, KCl, Na gluconate, K gluconate, or choline Cl. The result was a rapid efflux of water and a shrinking of the tubule, which could be measured by video techniques within the first 0.1 s. After reequilibration in isotonic medium, each tubule was then exposed to a second hypertonic medium to provide a direct comparison between two different solutes, either NaCl vs. KCl or raffinose vs. any one of the other solutes. Because raffinose is impermeant across the basolateral cell membrane, the ratio of its effect to that of another solute is a measure of the reflection coefficient (sigma) of that other solute. The following results were obtained: sigma KCl = 0.70 +/- 0.02, sigma K gluconate = 0.97 +/- 0.07, sigma Na gluconate = 0.84 +/- 0.06, and sigma choline Cl = 0.75 +/- 0.06. We previously have reported sigma NaCl = 0.56 +/- 0.07. If sigma of each salt is considered to be the arithmetic average of its component parts, and if gluconate and choline are considered to be impermeant, we also obtain sigma Na+ = 0.68, sigma K+ = 0.94, and sigma Cl- = 0.50. PMID- 2221099 TI - Effects of nifedipine and enalapril on glomerular injury in rats with deoxycorticosterone-salt hypertension. AB - Male Munich-Wistar rats underwent right nephrectomy and were given weekly injections of deoxycorticosterone acetate (DOCA) and 1% saline (salt) to drink. Two studies were performed. In the first, rats given enalapril (ENP) were compared with controls. In the second, rats ingested either standard chow or chow to which the calcium-entry blocker nifedipine (NIF) had been added. Six to eight weeks after nephrectomy, both control DOCA-salt rats and those given ENP had severe hypertension and significant proteinuria. Rats given NIF excreted less protein, and glomerular lesions were not observed in this group. The effects of NIF on several parameters that have been associated with glomerular injury were examined. Micropuncture studies revealed that glomerular capillary pressure was increased in DOCA-salt rats and was not reduced by NIF. Platelet aggregation was also similar in NIF-treated and control rats. Morphometric studies revealed a tendency toward lower glomerular volume of NIF-treated rats; however, kidney weight and glomerular capillary radius were unaffected by therapy. Thus NIF, but not ENP, prevents DOCA-salt rats from developing hypertension and glomerular injury. This effect does not depend on reduction in glomerular pressure or inhibition of platelet aggregation. PMID- 2221100 TI - Salicylic acid permeability properties of the rabbit cortical collecting duct. AB - To assess the role of nonionic diffusion of salicylic acid (pKa = 3) in the terminal nephron, we measured the passive permeability of [14C]salicylic acid in rabbit cortical collecting ducts isolated and perfused in vitro. This segment can produce and maintain a maximal pH gradient between blood and tubular fluid. When peritubular pH was kept constant at pH 7.4 the apparent permeability of salicylic acid (P', 10(-6) cm/s) was 6.2 +/- 1.1 at a luminal pH of 6.0, 17.2 +/- 5.3 at a luminal pH of 5.5, and 39.0 +/- 4.7 at a luminal pH of 5.0. These permeabilities were in close correlation with the percentage of nonionized salicylic acid present at each pH, indicating that only the nonionized molecule can diffuse across the collecting duct epithelium. By recalculating the permeability, taking into account only the concentration of the nonionized salicylic acid molecules, we obtained the apparent permeability of nonionized salicylic acid, which was no longer pH dependent and averaged 4,345 +/- 460 x 10(-6) cm/s. The apparent activation energy of this diffusion process was 9.3 +/- 1.2 kcal/mol as calculated from an Arrhenius plot. PMID- 2221101 TI - Depressed distal tubule acidification corrects chloride-deplete alkalosis in rats. AB - We investigated the relative contributions made by the proximal and distal tubule to the correction of Cl-deplete metabolic alkalosis induced by systemic administration of NaCl. Free-flow micropuncture was used to examine net bicarbonate reabsorption in superficial proximal and distal tubules of anesthetized Munich-Wistar rats during maintenance and correction of chronic furosemide-induced Cl-deplete metabolic alkalosis. The distal tubule of animals with correcting vs. maintained alkalosis had a lower fractional reabsorption of bicarbonate (38 vs. 75%, P less than 0.001) and a lower slope of the linear regression comparing absorption to delivered load (0.48 vs. 0.99, P less than 0.02). By contrast, proximal tubule of animals with correcting vs. maintained alkalosis had fractional reabsorption (85 vs. 90%, P = 0.07) and slopes of the regression comparing reabsorption to filtered load (1.09 vs. 0.98, P = 0.48) that were not different. The data indicate that correction of Cl-deplete metabolic alkalosis induced by NaCl administration involves a qualitative decreased in bicarbonate reabsorption in distal tubule with maintenance of the same load dependent relationship for bicarbonate reabsorption in proximal tubule. PMID- 2221102 TI - Renal actions of endothelin: interaction with prostacyclin. AB - The renal actions of endothelin were examined by infusing it intrarenally in anesthetized dogs at 4 ng.min-1.kg-1 without affecting arterial blood pressure or cardiac output. Endothelin infusion caused a transient and significant increase in renal blood flow (RBF) by 13 +/- 2%, followed by large decreases in RBF and glomerular filtration rate (GFR; by 26 +/- 2 and 23 +/- 7%, respectively) but did not alter urine flow rate or absolute sodium excretion. After endothelin infusion, renal venous and arterial plasma 6-ketoprostaglandin F1 alpha increased from 250 +/- 58 and 117 +/- 31 to 1,044 +/- 249 and 617 +/- 211 pg/ml, respectively, and its renal output increased from 339 +/- 99 to 963 +/- 202 pg.min-1.g-1 (P less than 0.01 for all). The renal prostacyclin synthesis was augmented by endothelin without stimulating the renal renin release or norepinephrine output. Inhibition of prostaglandin synthesis with indomethacin partially prevented the early renal vasodilation induced by endothelin, which then caused a more pronounced decline in RBF and GFR (by 65 +/- 7 and 54 +/- 8%, respectively). With suppression of prostacyclin synthesis, inhibition of renin release by endothelin was observed. Thus the vasoconstrictive effects of endothelin on renal hemodynamics are significantly modified by its ability to enhance production of vasodilators, including prostacyclin. PMID- 2221104 TI - Recruitment of renin gene-expressing cells in adult rat kidneys. AB - To define whether angiotensin I-converting enzyme (ACE) inhibition affects the distribution of renin gene-expressing cells within the kidney, a control group of adult male Wistar-Kyoto rats (C, n = 7) was compared with a group of rats treated with enalapril (E, n = 6) for 5 days. Renin mRNA distribution was assessed using in situ hybridization to a 35S-labeled 28 mer oligonucleotide complementary to rat renin mRNA. Whereas in control rats renin mRNA was confined to a juxtaglomerular location, in enalapril-treated rats, renin mRNA extended proximally along the length of the afferent arteriole. The percent of visible afferent arteriolar length containing renin mRNA was higher in enalapril-treated (71.7 +/- 2.8%) than in control (49.6 +/- 2.1%) rats (P less than 0.0001). These findings were accompanied by an increase in the percent of juxtaglomerular apparatuses (JGAs) containing renin mRNA (71 +/- 2.2 vs. 49 +/- 2.9%; E vs. C, P less than 0.0001). Also, the intensity of the JGA hybridization signals was higher in enalapril-treated (757 +/- 59 grains/JGA) than in control (167 +/- 11 grains/JGA) rats (P less than 0.00001). We conclude that the increased kidney renin gene expression elicited by ACE inhibition is the result of an increase in renin mRNA content per JGA, an increase in the number of JGAs expressing the renin gene, and a recruitment of renin gene-expressing cells along the afferent arteriole. PMID- 2221103 TI - Modulation of osmolytes in MDCK cells by solutes, inhibitors, and vasopressin. AB - MDCK cells accumulate organic osmolytes in response to hyperosmotic NaCl supplemented medium. We examined time course and inhibitor sensitivity of myo inositol, sorbitol, and glycerophosphorylcholine (GPC) accumulation in MDCK cells exposed to hyperosmotic NaCl-, D-glucose-, or mannitol-supplemented media. In NaCl medium, cells preferentially accumulated inositol and GPC. In comparison, in glucose medium cells preferentially accumulated sorbitol and GPC. Inositol demonstrated a late (72-96 h) accumulation in glucose medium, although less than in NaCl medium. Mannitol medium did not significantly stimulate accumulation of any of these three osmolytes at 24 h, suggesting that hyperosmolality alone is not sufficient stimulus for their accumulation in this time frame. GPC accumulation was very rapid in glucose medium, and fell to the level induced by NaCl medium at 96 h (approximately 50 nmol/mg protein). Inositol and sorbitol accumulated more gradually, each reaching greater than 400 nmol/mg protein after 96 h. Sorbitol was still accumulating at 96 h, whereas inositol plateaued at 72 96 h. Phlorizin or sorbinil blocked accumulation of inositol or sorbitol, respectively. Sorbitol and GPC accumulation in glucose medium were partially inhibited in absence of serum or in presence of 1 microM vasopressin. Thus NaCl and glucose appear to stimulate specific cellular mechanisms responsible for accumulation of inositol, sorbitol, and GPC in MDCK cells. This accumulation is also modulated by constituents of serum. PMID- 2221105 TI - Glucocorticoid receptors mediate mineralocorticoid-like effects in cultured collecting duct cells. AB - To investigate the direct epithelial effects of corticosteroids on renal ion transport, we studied the influence of the pure glucocorticoid agonist RU 28362 and aldosterone on Na+ and K+ transport in primary cultures of immunodissected rabbit cortical collecting duct (CCD) cells. When grown on permeable supports in a steroid-free medium, CCD monolayers exhibited a lumen-negative transepithelial potential difference (PD) of 5.2 +/- 1.07 mV and a short-circuit current (SCC) of 8.54 +/- 2.2 microA/cm2. Transepithelial resistance averaged 660 +/- 49 omega/cm2. The cultures actively reabsorbed Na+ and secreted K+. Both aldosterone and RU 28362 significantly increased PD and SCC; the effects were time and dose dependent. The effect of RU 28362 was completely prevented by the glucocorticoid receptor antagonist RU 486, whereas ZK 91587, a specific mineralocorticoid receptor antagonist, did not block its effect. Both aldosterone and RU 28362 increased the bath-to-lumen concentration ratio of Na+ while lowering that of K+, indicating an increased Na+ reabsorption and K+ secretion. The number of Na(+) K(+)-ATPase units was significantly enhanced (approximately 2-fold) by both RU 28362 and aldosterone. These results demonstrate that, in cultured CCD cells, not only aldosterone but also a pure glucocorticoid is able to exert mineralocorticoid-like effects, and this latter effect is mediated by glucocorticoid receptors. Because all parameters studied responded similarly to aldosterone and RU 28362, we speculate that in CCD cells glucocorticoids and mineralocorticoids might act by regulating the same gene(s). PMID- 2221106 TI - High glucose induces cell hypertrophy and stimulates collagen gene transcription in proximal tubule. AB - Tubulointerstitial changes in the diabetic kidney correlate closely with the decline in glomerular filtration. In this study, we used a cell culture system of mouse proximal tubule epithelial cells to test the effects of glucose on cell growth, size, and matrix biosynthesis. [3H]thymidine incorporation was significantly inhibited in cells grown in 450 mg/dl glucose, compared with cells grown in 100 mg/dl glucose. The cells grown in the higher glucose concentration were slightly larger, their protein content and the total protein synthetic rate were significantly increased, and they secreted approximately twice as much procollagens type IV and type I. Concordantly, steady-state procollagen mRNA levels were also increased: 2.6-fold for the alpha 1(IV) and 2.2-fold for the alpha 2(I) procollagens. Additionally, nuclear run-off studies demonstrated that procollagen gene transcription rate was stimulated approximately 50%; beta-actin transcription rate was not altered. We used chloramphenicol acetyltransferase (CAT) reporter gene constructs to determine whether the increased transcription rate of alpha 2(I) gene was associated with activation of its enhancer sequence. Cells transfected with the enhancer demonstrated more than fivefold increase in CAT activity when cultured in the high-glucose medium. These studies demonstrate a multitude of effects of high ambient glucose concentrations on proximal tubule cell growth and collagen biosynthesis; cell proliferation is decreased although cell hypertrophy occurs. Procollagen gene transcription rate is stimulated and this response contributes to the observed increase in procollagen mRNA content. Activation of an enhancer sequence may be one possible mode through which high glucose levels increase the transcription of procollagen type I, presumably involving trans-acting factor(s). PMID- 2221107 TI - Model of TGF-proximal tubule interactions in renal autoregulation. AB - Previous models, assuming constant reabsorption in the proximal tubule, have shown that tubuloglomerular feedback (TGF) can explain only a fraction of glomerular filtration rate (GFR) and renal blood flow autoregulation. Increased arterial pressure inhibits proximal tubule fluid reabsorption, an effect that should increase the efficacy of TGF because of the resulting increased flow rate in the loop of Henle. Models describing pressure and flow in a glomerulus and a nephron were derived to test this prediction. The models were coupled by a TGF function with tubular flow rate at the end of the proximal tubule (superficial nephron) or at the macula densa (juxtamedullary nephron) as input and with afferent arteriolar resistance as output. In agreement with others, the model predicted that TGF alone could account for about one-half of autoregulation. Pressure-dependent inhibition of proximal reabsorption increased the ability of TGF to account for autoregulation, providing compensation for increases in arterial pressure comparable to published whole kidney values. The inclusion of an approximation of an effect of arterial pressure on TGF marginally improved predicted autoregulation. Although the results suggest that the proximal tubule TGF interaction can provide a quantitatively adequate explanation for autoregulation, they also indicate that the effect of the interaction is spent at arterial pressures greater than 130 mmHg. Additional mechanisms are required to extend this range. PMID- 2221108 TI - Thapsigargin demonstrates calcium-dependent regulation of phosphate uptake in HeLa cells. AB - We used thapsigargin, a sesquiterpene lactone that mobilizes intracellular Ca without increases in inositol phosphates or major activation of protein kinase C (PKC), to test the specific effects of increasing cytosolic Ca on Na-dependent phosphate uptake in HeLa cells. Thapsigargin increased the Vmax for phosphate uptake from 5.40 +/- 0.26 to 7.86 +/- 0.43 nmol.mg protein-1.3 min-1 (n = 7, P less than 0.001) without change in the apparent Km for phosphate, which averaged 0.15 +/- 0.02 mM. The effect of thapsigargin was dependent on concentration and time. Inactivation of PKC by overnight exposure to 16 microM phorbol 12,13 dibutyrate did not eliminate the effect of thapsigargin, although it completely abolished the effects of phorbol ester on phosphate uptake. Thus thapsigargin are not dependent on PKC. As in other cell systems, thapsigargin increased cytosolic Ca concentration. Removal of extracellular Ca diminished the increase in cytosolic Ca and eliminated the effect of thapsigargin on phosphate uptake. Collectively, our data indicate that Na-dependent phosphate uptake in HeLa cells can be regulated by at least three specific signaling pathways: protein kinase A, PKC, and increased cytosolic Ca. PMID- 2221109 TI - Compliance of left atrium with and without left atrium appendage. AB - Compliance of the left atrial chamber was estimated with and without the appendage intact in six isolated canine left atria. Pressure-volume determinations were measured over a range of 5-30 mmHg for the whole left atrium and were repeated with the appendage excluded. The slope of the pressure vs. normalized volume data for the left atrium without the appendage (10.45 +/- 0.87) was significantly greater (P less than 0.01) than with the appendage intact (4.10 +/- 0.72). These data suggest that the left atrial appendage is more compliant than the remaining left atrium. Assuming that this relationship remains in vivo, the left atrial appendage may play an augmented role in maintaining hemodynamic function when filling pressures are elevated. PMID- 2221110 TI - Temporal analysis of myocardial glucose metabolism by 2-[18F]fluoro-2-deoxy-D glucose. AB - To assess kinetic changes of myocardial glucose metabolism after physiological interventions, we perfused isolated working rat hearts with glucose and 2 [18F]fluoro-2-deoxy-D-glucose (2-FDG). Tissue uptake of 2-FDG and the input function were measured on-line by external detection. The fractional rate of 2 FDG phosphorylation was determined by graphical analysis of time-activity curves. The steady-state uptake of 2-FDG was linear with time, and the tracer was retained predominantly in its phosphorylated form. Tissue accumulation of 2-FDG decreased with a reduction in work load and with the addition of competing substrates. Insulin caused a significant increase in 2-FDG accumulation in hearts from fasted but not from fed animals. We conclude that in the isolated working rat heart there is rapid adjustment of exogenous substrate utilization and that most interventions known to alter glucose metabolism induce parallel changes in 2 FDG uptake. Qualitative differences in the in vitro response to insulin may be affected by the presence of either endogenous insulin or glycogen. PMID- 2221111 TI - Loss of vascular responsiveness induced by endotoxin involves L-arginine pathway. AB - The involvement of L-arginine-dependent nitric oxide (NO) production in the vascular failure observed in endotoxemia was investigated in male Wistar rats treated with Escherichia coli lipopolysaccharide (LPS). Contractile responses to norepinephrine (NE) were measured ex vivo in aortas isolated from rats treated with LPS (20 mg/kg ip, 4 h before experiments) and pressor responses to NE were recorded in vivo in rats infused with LPS (5 mg.kg-1.h-1 iv). LPS pretreatment induced a rightward shift of the concentration-response curve to NE and a reduction of the maximal contraction by approximately 43% and 54% (P less than 0.05) in aortic rings with and without functional endothelium, respectively. This was not modified by the presence of indomethacin (10 microM) during the contractile experiments. In contrast, in the presence of NG-monomethyl-L-arginine (L-NMMA, 300 microM) or methylene blue (10 microM), maximal contractions to NE were restored to control values whether functional endothelium was present or not. The effects of L-NMMA were reversed by L- but not by D-arginine. Additionally, the effects of LPS pretreatment on vascular contractility were potentiated by L-arginine. In vivo, LPS infusion produced a reduction in pressor responsiveness to NE (0.1-10 mg/kg), which was also abolished by L-NMMA (30 mg/kg iv). This effect of L-NMMA was reversed by L- but not by D-arginine (100 mg/kg iv). These results demonstrate that activation of the L-arginine pathway has a major role in the production of vascular hyporeactivity in endotoxemia, ex vivo as well as in vivo. Additionally, they suggest that endothelium-independent vascular production of NO may be involved. PMID- 2221112 TI - Identification of major slow blood pressure oscillations in conscious dogs. AB - All physiological feedback systems (e.g., in arterial pressure control) tend to oscillate in a characteristic manner. Mechanoreceptors can effectively buffer resulting fluctuations in arterial blood pressure. In this study arterial and cardiopulmonary receptors were interrupted in eight conscious foxhounds by sectioning the afferent pathways to the central nervous system. In response, three major peaks were detected in the blood pressure power spectrum: in addition to the well-known rhythms reflecting heart rate and respiration, very slow oscillating waves with a cycle length of 20 +/- 4 min and a 10(5)-fold higher power than the other two waves were detected. The amplitude of these oscillations could exceed 100 mmHg. This peak was also identified under control conditions (at a cycle length of 21 +/- 4 min, n = 6); however, the relative power was greater than 10(3)-fold less with mechanoreceptors intact (P less than 0.001). Thus a major slow oscillating component of arterial pressure control has been identified. Normally, mechanoreceptors buffer the resulting waves of this oscillator. These very strong fluctuations may characterize an important feature of blood pressure regulation. PMID- 2221113 TI - Endothelium-dependent, flow-induced dilation of isolated coronary arterioles. AB - Flow-mediated dilation has been documented in large conduit coronary arteries but not in coronary arterioles. The goal of this study was to determine whether this response occurs in coronary arterioles and whether it competes with myogenic constriction. Subepicardial arterioles (40-80 microns) were isolated and cannulated with two glass micropipettes connected to independent reservoir systems. During zero flow, myogenic responses were studied over the range of intraluminal pressure (IP) between 20 and 140 cmH2O. Myogenic constrictions and dilations was observed when IP was increased (greater than 60 cmH2O) and decreased (less than 60 cmH2O), respectively. Flow was initiated by simultaneously moving the reservoirs in equal and opposite directions, thus generating a pressure gradient (delta P) without changing the mean luminal pressure (range delta P = 4-60 cmH2O). Flow-induced responses were studied at low, intermediate, and high myogenic tones by setting IP at 20, 60, and 100 cmH2O, respectively. The threshold for flow-induced dilation was delta P = 4 cmH2O, and maximum dilation was observed at delta P = 20 cmH2O. Red cell velocities in isolated arterioles at delta P of 4 and 60 cmH2O were 1.2 +/- 0.2 and 15.9 +/- 1.3 mm/s, respectively, which are within the range of those reported for coronary microvessels in vivo. The magnitude of the flow-induced dilation was greatest at the intermediate tone (60 cmH2O IP) but was attenuated at lower and higher IP. After mechanical removal of the endothelium, spontaneous tone and myogenic responses were preserved, but flow-induced dilation and bradykinin induced dilation were abolished.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221114 TI - Deformation response of red blood cells in oscillatory shear flow. AB - The characteristics of red cell deformation were studied, focusing on deformation response of the cells subjected to oscillatory shear stress. Red blood cells were fractionated into subpopulations of different densities, i.e., low-density and high-density cells. The deformation response of the fractionated cells was evaluated with a rheoscope varying their intracellular viscosity and oscillation frequency of the applied shear stress, and determinants of the deformation response were compared with those of whole cell deformation under stationary shear stress. When the fractionated cells were exposed to sinusoidally oscillated shear stress, the cells underwent oscillatory deformation. The degree of deformation of the low-density cells correspond to the magnitude of the applied shear stress up to an oscillation frequency of 2.7 Hz. Meanwhile, such an oscillatory deformation as to correspond to the applied shear stress was observed up to 1.7 Hz for the high-density cells. It was suggested that intracellular viscosity was an important factor to determine the deformation response of red cells to oscillatory shear stress. PMID- 2221115 TI - Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts. AB - We have previously shown that high concentrations of fatty acids depress reperfusion recovery of ischemic rat hearts as a result of a fatty acid inhibition of glucose oxidation. In this study, we determined whether dichloroacetate, an activator of pyruvate dehydrogenase, could overcome fatty acid inhibition of glucose oxidation and thereby improve mechanical recovery of hearts reperfused after a period of transient global ischemia. Isolated working rat hearts, perfused with 11 mM glucose, 1.2 mM palmitate, and 500 microU/ml insulin, were subjected to a 30-min period of no flow ischemia, followed by a 30 min period of reperfusion. Under these conditions, control hearts recovered 37% of preischemic function. The addition of 1 mM dichloroacetate to the perfusate at reperfusion resulted in a significant improvement in recovery of mechanical function (to 73% of preischemic function). When dichloroacetate was added before the onset of ischemia, however, this protective effect was lost, and a significant increase in myocardial lactate accumulation during ischemia was observed. The effects of dichloroacetate on glucose oxidation rates in both nonischemic and reperfused ischemic hearts was determined by perfusing hearts with 11 mM [U-14C]glucose and 1.2 mM palmitate and quantitatively collecting 14CO2 produced by the heart. In nonischemic hearts, 1 mM dichloroacetate increased steady-state glucose oxidation rates from 298 +/- 69 to 1,223 +/- 135 nmol.g dry wt-1.min-1. The addition of dichloroacetate to hearts reperfused after a 25-min period of ischemia also increased glucose oxidation rates from (112 +/- 25 to 561 +/- 83 nmol.g dry wt-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221117 TI - Hyaluronan in prenodal lymph from skin: changes with lymph flow. AB - Hyaluronan, an important structural component of the interstitial matrix in skin, is found in lymph to be subsequently degraded in lymph nodes and liver. Hyaluronan concentration and flux were measured in prenodal lymph from the hindpaw in six pentobarbital-anesthetized mongrel dogs at normal and increased transvascular fluid flux. Lymph flow and hyaluronan concentration in control averaged 16.3 +/- 15.0 (SD) microliters/min (range 6.3-46.5) and 6.16 +/- 3.78 micrograms/ml, respectively. Lymph flow was increased stepwise by raising venous pressure, and measurements were performed at each step after three consecutive and identical measurements of lymph flow and protein concentration taken 15 min apart. Hyaluronan concentration was unchanged until venous pressure was raised above 20 mmHg and then gradually fell to an average of 4.8 +/- 2.67 micrograms/ml at venous pressures around 40 mmHg. The lymphatic hyaluronan flux averaged 0.085 +/- 0.034 micrograms/min in control and 0.28 +/- 0.14 micrograms/min at the highest flows (4.3 times control), draining 2% and 10% of the total interstitial hyaluronan in the tissue in 24 h, respectively. The results suggest that at least part of the hyaluronan in skin is loosely bound and easily removed via lymph. PMID- 2221116 TI - Severe myocardial dysfunction induced by ventricular remodeling in aging rat hearts. AB - To determine if aging engenders alterations in the functional properties of the myocardium and ventricular remodeling, the hemodynamic performance and structural characteristics of the left ventricle of male Fischer 344 rats at 4, 12, 20, and 29 mo of age were studied by quantitative physiology and morphology. In vivo assessment of cardiac pump function showed no change up to 20 mo, whereas left ventricular end-diastolic pressure was increased at 29 mo. Moreover, peak rates of pressure rise and decay, stroke volume, ejection fraction, and cardiac output were depressed at the later age interval, demonstrating the presence of ventricular failure at this time. The measurements of chamber size and wall thickness showed that ventricular end-diastolic and end-systolic volumes progressively increased with age with the greatest change occurring at 20-29 mo. Aging was also accompanied by a marked augmentation in the volume fraction of fibrotic areas in the ventricular myocardium that was due to an increase in their number and cross-sectional area with time. These architectural rearrangements, in combination with the abnormalities in ventricular function, resulted in an elevation in the volume of wall stress throughout the cardiac cycle. Wall stress increased by 64, 44, and 50% from 4 to 12, 12 to 20, and 20 to 29 mo of age. In conclusion, aging leads to a continuous rise in wall stress that is not normalized by ventricular remodeling. These two independent processes appear to be responsible for the onset of heart failure in the senescent rat. PMID- 2221118 TI - Role of iron on membrane phospholipid breakdown in ischemic-reperfused rat heart. AB - Oxygen-derived free radicals have been implicated in causing degradation of myocardial membrane phospholipids associated with ischemia and reperfusion. Since iron is known to catalyze the hydroxyl radical formation responsible for cellular injury, this study was designed to relate the role of iron with phospholipid breakdown in ischemic-reperfused heart. Isolated rat heart perfused by the Langendorff technique was subjected to 30 min of normothermic ischemia followed by 30 min of reperfusion. The experimental group received 0.6 mM deferoxamine, an iron chelator, before reperfusion of ischemic myocardium. Deacylation and reacylation of membrane phospholipids were monitored by using [14C]arachidonic acid (AA), whereas the de novo phospholipid synthesis was evaluated by using [3H]glycerol in the perfusate. In the deferoxamine group, the loss of [14C]phosphatidylcholine (PC) and the corresponding accumulation of isotopic lysophosphoglycerides as well as AA was significantly lower compared with the control. The incorporation of radioactivity for [14C]AA and [3H]glycerol into phospholipids was significantly increased in the treated group compared with the untreated group. In addition, decreased malonaldehyde formation and lactate dehydrogenase release, a higher recovery of high-energy phosphate compounds, and myocardial contractility were noticed in the deferoxamine-treated hearts. These results indicated that postischemic administration of an iron chelator such as deferoxamine can preserve membrane phospholipids and reduce myocardial dysfunction associated with reperfusion of ischemic heart. PMID- 2221119 TI - Cardiac effects induced by chemically activated neurons in canine intrathoracic ganglia. AB - Regional or global cardiac responses were elicited when various chemicals were injected into discrete loci within acutely decentralized stellate and middle cervical ganglia. Nicotine (100 micrograms), acetylcholine (100 micrograms), or isoproterenol (1, 2, or 5 micrograms) in 1 microliters of normal saline was administered individually into 30 discrete loci within each stellate ganglion and 25 within each middle cervical ganglion. Cardiac augmentation was elicited when approximately 1 site per ganglion was injected with nicotine or acetylcholine. Similar injections into sites approximately 1-2 mm away from an active site usually failed to elicit cardiac responses. Isoproterenol elicited cardiac augmentations when injected into, on average, 3 different loci per ganglion. The responses elicited by isoproterenol injections were eliminated when the efferent sympathetic nerves arising from an injected ganglion were divided or when timolol maleate (0.1 mg/microliters normal saline) was previously injected into the same locus. These data indicate that the effects elicited by injecting isoproterenol into an intrathoracic ganglion locus were not due to leakage of this agent into the blood in sufficient quantities to directly activate cardiac myocytes. When L glutamic acid (100 microliters of 1 M solution in normal saline) or L-aspartic acid (100 microliters of 1 M solution in normal saline) was injected into a stellate ganglion or middle cervical ganglion, positive chronotropic and/or inotropic responses were elicited. When DL-homocysteic acid (100 microliters of 1 M solution in normal saline) was administered no augmentation occurred. It is concluded that intrathoracic ganglion cardiac neurons can be activated by nicotinic or beta-adrenergic agonists, as well as by specific amino acids. These neurons are located throughout the stellate and middle cervical ganglia, cardiac neurons in one ganglionic locus being capable of activation by more than one of these chemicals. PMID- 2221120 TI - Unloaded shortening velocity of skinned rat myocardium: effects of volatile anesthetics. AB - The slack test method has been adapted for measurement of unloaded velocity of shortening in rat ventricular trabeculae that were skinned with saponin (50 micrograms/ml for 30 min). The method was sensitive enough to detect a 17% reversible change in the unloaded velocity of shortening produced by a 3 degrees C change in temperature. At pCa 5.30 (80-90% activation), halothane, enflurane, and isoflurane each slowed the shortening velocity by 25-30% at dose levels of 8 mM or greater but not at 4 mM or less. At pCa 5.48 (50-60% activation), halothane slowed the shortening velocity by 20-45% at dose levels of 4 mM or greater but not at 2 mM. The slowing effect of anesthetics on shortening velocity showed saturation at 8 mM for halothane, enflurane, and isoflurane when activation was at pCa 5.30. Saturation occurred at 4 mM for halothane when the pCa was 5.48. This result indicates that the dose-response relationship may be narrow, such that it can be demonstrated between 2 and 4 mM halothane for pCa 5.48 and between 4 and 8 mM halothane for pCa 5.30. The anesthetic dose dependence of isometric force and length axis intercept did not generally follow the same relationship as for the shortening velocity. Thus in several instances force did not significantly decrease when the velocity of shortening did. This may be interpreted as lack of simple inhibition by anesthetics on the number of interacting cross-bridges and as direct influence by anesthetics on the cross bridge cycle. PMID- 2221121 TI - Differential effects of hemorrhage on adrenal and renal nerve activity in anesthetized rats. AB - Evidence that sympathetic outflow to organs with different functions reacts nonuniformly to various stimuli has accumulated. To clarify the difference in outflow characteristics of adrenal and renal nerves, the neural and neurochemical mechanisms involved in the response to hemorrhage were examined in anesthetized rats. Hemorrhage (2, 5, and 10 ml/kg) increased adrenal nerve activity (ANA) and decreased renal nerve activity (RNA) in a bleeding volume-dependent manner, accompanied with a decrease in mean arterial blood pressure and heart rate. Bilateral vagotomy attenuated the response in ANA and completely abolished the response in RNA. Sinoaortic denervation (SAD) and vagotomy combined with SAD inversely decreased ANA during hemorrhage. However, SAD appears to have no effect on the response in RNA, which was completely abolished by combined denervation. Our results suggest that the differential effects of hemorrhage on ANA and RNA may be due to different contributions via the afferent neural pathways from the baro- and cardiopulmonary receptors. Because naloxone attenuated the dissociated response to hemorrhage, the endogenous opioid system may be involved. PMID- 2221122 TI - Oxygen consumption is less in rat hearts arrested by low calcium than by high potassium at fixed flow. AB - The purpose of the present study was to determine whether myocardial oxygen consumption (MVO2) differs when the heart is arrested by hyperkalemic arresting solution (ASK) or by hypocalcemic arresting solution (ASCa) when coronary flow is maintained constant. MVO2 was measured in 12 isolated, Langendorff-perfused rat hearts alternately perfused with ASK (20 mM K+ and 1.5 mM Ca2+) and ASCa (5 mM K+ and 0.08 mM Ca2+). Six of the hearts were perfused with ASK for 10 min, ASCa for 5 min, ASK for a second 5 min, and finally ASCa for 5 min; ASCa and ASK were opposite in this sequence for the other six hearts. Measurements of MVO2 during ASK and ASCa arrest, taken at the end of each perfusion period, were analyzed to distinguish the independent influences of time and perfusate composition on MVO2 in the arrested hearts (analysis of covariance). Consistent with previous findings, MVO2 decreased with time after the onset of cardiac arrest with both solutions. The average per minute fall was 0.0003 ml O2.min-1.g-1 (P less than 0.01). However, at any given time after arrest, MVO2 averaged 0.004 ml.min-1.g-1 less during ASCa arrest than during ASK arrest (P less than 0.01), which amounted to a 15% reduction in MVO2. To test whether the increased MVO2 during hyperkalemic arrest was dependent on calcium in the perfusion medium, a third series of six hearts was studied in which MVO2 values measured during ASCa and ASK arrest were compared with those measured during arrest by hyperkalemic hypocalcemic solution (ASK,Ca: 20 mM K+, 0.08 mM Ca2+).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221123 TI - Role of endocardial endothelium in positive inotropic action of vasopressin. AB - We have studied the effects of vasopressin on isolated cat papillary muscle both before and after damaging the endocardium. The experiments were performed in physiological conditions of temperature (35 degrees C) and calcium concentration (1.25 mM Ca2+). Isometric and isotonic twitches as well as maximal unloaded velocity of shortening (Vmax) were measured. In muscles with an intact endocardium (n = 13), vasopressin (10(-12) to 10(-6) M) induced early twitch relaxation with a significant reduction of time to half isometric tension decline and with concomitant significant decrease in peak twitch performance. In a second group of muscles (n = 13) the endocardial endothelial surface was damaged by briefly (1 s) exposing the muscles to a 0.5% Triton X-100 followed by abundant wash with Krebs-Ringer solution, thereby irreversibly decreasing time to half twitch relaxation and peak twitch tension without significantly affecting Vmax. After this intervention, vasopressin had a positive inotropic effect with a significant increase in peak twitch tension and Vmax with no significant changes in twitch duration. Accordingly, in the presence of a functional endocardium, the direct myocardial positive inotropic effect of vasopressin was reversed, with early twitch relaxation and diminished peak twitch performance. At the highest concentrations of vasopressin, vasopressin-induced functional and morphological damage of the endocardium was observed. PMID- 2221124 TI - Diaphragm does not produce ammonia or lactate during high-intensity short-term exercise. AB - To ascertain whether costal diaphragm engages in ammonia and lactate production (like limb muscles) during high-intensity short-term exercise, experiments were carried out on six healthy trained ponies in which phrenic venous catheters had been implanted 5-9 days earlier. Simultaneous anaerobically obtained blood samples from abdominal aorta and the phrenic vein at rest and during 4 min of exertion at 32 km/h and at a 7% grade were analyzed for blood-gas variables as well as lactate and ammonia concentrations using standard procedures. At rest, heart rate was 47 +/- 4 beats/min and the diaphragmatic O2 extraction was 26.5%. With exercise, heart rate rose to 218 +/- 6 beats/min, marked acidosis and hyperventilation occurred, and the diaphragmatic O2 extraction increased threefold (80.9%). Such exercise is known to dramatically increase the work of breathing as respiratory frequency and change in pleural pressure approach 138 +/ 4 breaths/min and 30 +/- 3 cmH2O, respectively. Despite the fact that phrenic venous O2 tension of exercised ponies decreased to 15.5 +/- 0.6 Torr, the phrenic venous lactate and ammonia concentrations did not exceed corresponding arterial values. These data thus revealed that the diaphragm is uniquely unlike limb muscles, which at high workloads readily engage in net ammonia and lactate production, and that the diaphragmatic energy needs during high-intensity short term exercise are primarily met by aerobic metabolism. PMID- 2221125 TI - Myocardial high-energy phosphates in reactive hyperemia. AB - This study used 31P nuclear magnetic resonance (NMR) spectroscopy to determine whether the magnitude and duration of myocardial reactive hyperemia (RH) reflect a commensurate derangement of myocardial high-energy phosphate (HEP) metabolism, or if coronary blood flow (CBF) and HEP metabolism are dissociated during RH. Twelve open-chest anesthetized pigs were studied during and after 24 s occlusion of the anterior descending coronary artery. CBF velocity was measured with a Doppler probe. NMR time resolution (4.8 s) was obtained by summing corresponding short blocks of data from multiple occlusions. During occlusion, phosphocreatine (PCr) declined to 65 +/- 5% (mean +/- SE) of control accompanied by increased spectral intensity of the Pi + phosphomonester region. By 20 s of reflow, HEPs had returned to control levels, but CBF was still elevated at 282 +/- 18% of control and remained elevated for an additional 53 +/- 7 s, during which 44 +/- 6% of total RH flow occurred. Therefore, the control of CBF is not closely coupled to the levels of myocardial HEPs during RH and the duration of RH does not reflect prolonged depletion of myocardial HEPs. PMID- 2221127 TI - Activity of canine in situ left atrial ganglion neurons. AB - The responses of 135 spontaneously active neurons were recorded from ganglionated plexi located in the three epicardial fat pads on the ventral surface of the left atrium of ten dogs. Ganglia, some of which were adjacent to the recording sites, containing varying numbers of neurons were identified throughout these fat pads. Spontaneous activity in 50% of the identified neurons was correlated with specific phases of the cardiac cycle when arterial systolic pressure was between approximately 70 and 180 mmHg and in 28% it was correlated with the respiratory cycle. More neurons displaying cardiovascular-related activity were recorded when systolic pressure was increased after administration of positive inotropic agents or aortic occlusion. However, when systolic pressure increased above approximately 150 mmHg the number of active neurons decreased, and when pressure reached approximately 180 mmHg no activity was recorded. The activity of 36% of identified neurons was altered when discrete regions of the heart, great thoracic vessels, lungs, neck, upper limb, chest wall, or abdominal wall were mechanically distorted by gentle touch. After acute decentralization of the intrathoracic nervous system some neurons still displayed spontaneous cardiovascular- or respiratory-related activity. Single stimuli or trains of stimuli delivered to the vagosympathetic complexes, stellate ganglia, or cardiopulmonary nerves activated neurons in intact or acutely decentralized preparations. It is concluded that ventral left atrial ganglionated plexi neurons display activity related to cardiovascular or respiratory dynamics, and that these neurons are influenced by sympathetic and parasympathetic efferent axons, as well as by cardiac and other mechanoreceptors. PMID- 2221126 TI - Sympathetic activity during graded central hypovolemia in hypoxemic humans. AB - To determine how hypoxemia (Hx) might alter muscle sympathetic nerve activity (MSNA) (microneurography, peroneal nerve), norepinephrine (NE) levels, and vasoconstriction during mild central hypovolemia, we exposed eight men to continuous graded lower body negative pressure (LBNP) (-5, -10, -15, -20, and -25 mmHg, 5 min per level) during both Hx (10 or 12% O2) and normoxia (Nx). Hx significantly augmented MSNA during LBNP. Total MSNA (average amplitude X burst frequency) rose at each level of LBNP by 2, 28, 93, 61, and 123% (Nx) and 32, 110, 127, 179, and 216% (Hx). Only at LBNP -20 and -25 mmHg did Hx significantly augment the increase in forearm venous NE concentration. Arterial pressure was unaffected by LBNP in Nx and Hx. Forearm blood flow (venous occlusion plethysmography) fell, and forearm vascular resistance (FVR) rose 23, 53, 65, 67, and 86% (Nx) vs. 22, 23, 60, 69, and 87% (Hx), but increments in FVR (absolute units) were significantly less in Hx. Correlations among MSNA and other variables were insignificant for pooled data owing to large inter-individual variations in slopes, but correlations were significant for total MSNA (and burst frequency) vs. FVR (Nx) and NE (Hx). Three men released epinephrine during LBNP; this was accompanied by forearm vasodilation and falling pressure, and in two men, decreased MSNA and bradycardia occurred (i.e., vasovagal reaction). Overall, we found no major defect in sympathetic control during graded hypovolemia and Hx as long as epinephrine levels did not rise. PMID- 2221128 TI - Contraction and sarcoplasmic reticulum Ca2+ content in single myocytes of guinea pig heart: effect of ryanodine. AB - The relationship between the ability of sarcoplasmic reticulum (SR) to accumulate and retain Ca2+ and the electrically stimulated contractions (ESCs) of isolated cells from guinea pig ventricular myocardium was investigated. Caffeine contractures or rapid cooling contractures were used as a relative measure of the SR Ca2+ content. Depletion of SR Ca2+ by short exposure to caffeine (15 mM) or by prolonged rest resulted in a reduction of the amplitude of the ESCs by 83 +/- 14 and 65 +/- 11% (means +/- SD), respectively. This result points to SR as a major source of the Ca2+ that activates contraction. However, depriving the SR of the ability to retain Ca2+ by means of prolonged (up to 75 min) exposure to 0.1 microM ryanodine (as shown by the absence of contractile response to caffeine or cooling) did not prevent an ESC of nearly normal amplitude (81 +/- 24% control), albeit with a reduced contraction velocity and a time to peak contraction prolonged by 51 +/- 11%. Additionally, while rest decay of ESCs was present after ryanodine treatment, the time for the ESCs to recover their steady-state amplitude was prolonged at least twofold. Thus, in contrast with the normal guinea pig cells, ESCs of the myocytes exposed to ryanodine are controlled by sarcolemmal processes. This change in the state of excitation-contraction coupling results mainly in modification of the time course of the ESCs and of the time course of the response of the cells to the change in the rate of stimulation. PMID- 2221129 TI - Perinatal aortic growth in lambs: relation to blood flow changes at birth. AB - We have examined aortic growth and aortic hemodynamics in lambs in the perinatal period. Morphometry of histological cross sections indicated that abdominal aortic circumference decreased by 31% between 131 days of gestation and 2-3 wk postpartum. In contrast, the internal circumference of the thoracic aorta increased by 34% over the same time interval; thus size reduction of the abdominal aorta was not part of a generalized arterial response to ex utero life. We also determined medial cross-sectional area as an index of medial tissue mass. In the perinatal period (120 days gestation to 21 days postpartum), this index increased by 144% for the thoracic aorta but only by 69% in the abdominal aorta. Differences in rate of medial tissue accumulation were much greater postpartum than in utero. The relationship between abdominal aortic growth and hemodynamic changes was examined by instrumenting fetal lambs with blood pressure catheters, abdominal aortic blood velocity transducers, and sonomicrometer diameter crystals mounted on the abdominal aorta. Parturition, and the consequent loss of the placental circulation, caused a 73% reduction in abdominal aortic blood velocity. Abdominal aortic external diameter in the period between 4 and 14 days postpartum was reduced significantly compared with in utero values. These data are consistent with the hypothesis that blood flow changes at birth significantly influence arterial growth postpartum. PMID- 2221130 TI - Regional autoregulatory responses during infusion of vasoconstrictor agents in conscious dogs. AB - We investigated pressure-dependent autoregulatory responses in mesenteric, iliac, and renal vascular beds of conscious dogs during intravenous infusion of angiotensin II, phenylephrine, or arginine vasopressin at rates which increased arterial pressure by 20-40 mmHg. The arteries supplying these beds were instrumented with an electromagnetic flow probe, a nonoccluding catheter, and an electromagnetic flow probe, a nonoccluding catheter, and an occluder cuff connected with a servo-amplifier, which enabled us to return perfusion pressure to control levels during infusion of the vasoconstrictor agents. We attempted to differentiate between the increase in vascular resistance due to the direct effect of the vasoconstrictor agent and the increase induced by an autoregulatory response induced by elevations of aortic perfusion pressure. We measured a strong degree of autoregulation in the renal vascular bed with a fractional compensation value close to 1. Moderate autoregulation occurred in the mesenteric vascular bed, where the compensation was 0.4-0.5 with angiotensin II and phenylephrine and between 0.74 and 0.94 with vasopressin. No autoregulatory capacity could be demonstrated in the hindlimb. The findings indicate that, under conditions of increased systemic blood pressure, both the renal and the mesenteric vascular beds contribute to the increase in total peripheral resistance by pressure dependent vasoconstrictor responses. PMID- 2221132 TI - Neutrophil-mediated vascular leakage is not suppressed by leukocyte elastase inhibitors. AB - Application of leukotriene B4 (LTB4) to hamster cheek pouches induces neutrophil dependent vascular leakage of macromolecules as well as leukocyte intravascular adherence and emigration. The effect of inhibitors of neutrophil elastase on these reactions was studied with intravital microscopy. Anesthetized hamsters were pretreated with the elastase inhibitors L 658,758, Eglin C, or dextran sulfate, and LTB4 (10 nM) was superfused over the cheek pouches. Neither Eglin C nor L 658,758 had any effect on the resulting vascular leakage of a macromolecular marker; in contrast, dextran sulfate suppressed this leakage by 85%. None of the compounds affected LTB4-induced leukocyte adherence or neutrophil diapedesis. The inhibitors were able to inhibit both hamster and human neutrophil elastase as estimated in crude neutrophil extracts. These results suggest that neutrophils extravasate and generate vascular leakage without the use of their elastase activity. The inhibitory effect of dextran sulfate on macromolecular leakage may be due to interaction with cationic proteins released from the neutrophils. PMID- 2221131 TI - BBB transport and rapid tissue binding of cyclofoxy: comparison of active and inactive enantiomers. AB - The "rapid-phase" brain distribution of 3H-labeled enantiomers of the opiate receptor antagonist cyclofoxy (CF), receptor active (-) and inert (+) forms, was measured during 20- to 180-s intravenous infusion in rats. [14C]iodoantipyrine was coinfused during these experiments to obtain a simultaneous measure of blood flow. The influx clearance (K1) across the blood-brain barrier (BBB) and the rapid binding equilibrium constant (Keq) were estimated in different brain regions for both enantiomers (2-compartmental model); a possible receptor binding process (k3) was also examined for (-)-CF (3-compartment model). K1 (0.46-0.91 ml.min-1.g-1), the capillary permeability-surface area product (PS; 0.75 approximately 1.4 ml.min-1.g-1) and the tissue extraction fraction (E; 0.6-0.7) were found to be identical for both enantiomers in the nonreceptor binding model; Keq was identical in cerebellum but larger for (-)-CF in other brain structures. The difference in Keq between the enantiomers (2-compartment model) correlated with the rank order of opiate receptor density observed in vitro and in vivo. These results suggest that concomitant use of (-)-CF and (+)-CF will be useful for in vivo receptor binding analyses. PMID- 2221134 TI - A method to estimate the point at which two lines intersect from noisy data. PMID- 2221133 TI - Adenosine and active hyperemia in soleus and gracilis muscle of cats. AB - Exercise-induced increases in tissue adenosine level vary in muscles having different oxidative capacities. These studies were designed to further evaluate the role of this potent vasodilator as a modulator of active hyperemia in muscles having different intrinsic metabolic profiles. Soleus (slow-twitch oxidative) and gracilis (fast-twitch glycolytic) muscles of anesthetized cats were stimulated to contract isometrically in the presence of adenosine deaminase (ADA) or ADA that had been deactivated by boiling (BADA). Stimulation parameters were chosen to provide similar high and low blood flow responses in the two muscle types. ADA did not affect resting blood flow or vascular resistance. In the soleus muscle, ADA attenuated both the increase in blood flow and oxygen consumption and the decrease in vascular resistance at the high level of muscle stimulation. In addition, muscle performance decreased to 60% of its initial level in the presence of ADA, although the same initial performance level was maintained over the stimulation period during BADA infusion. Temporal studies in the soleus muscle demonstrated an ADA-induced decrease in oxygen consumption, which was the product of an attenuated blood flow, followed by reductions in muscle performance. ADA had no effect on active hyperemia in either muscle at the low stimulation level. Additionally, ADA did not attenuate active hyperemia in the gracilis when stimulated at a level that normally produced muscle fatigue. Therefore these data support a role for adenosine in mediating vasodilation in skeletal muscle composed of high-oxidative fibers at high levels of muscle performance but do not support a role for adenosine in skeletal muscle having low oxidative fibers, even at levels of exercise which produce fatigue. PMID- 2221135 TI - A method for continual monitoring of bone resorption in rats: evidence for a diurnal rhythm. AB - A method has been developed to monitor bone resorption (BR) based on the urinary excretion of [3H]tetracycline ([3H]TC) from chronically prelabeled rats. This is possible because the [3H]TC released from bone has been found to be in a form that is not or only poorly bound to apatite and thus not reincorporated into newly formed bone. When BR was increased by means of dietary calcium restriction, parathyroid hormone (PTH) infusion, or retinoid injections, urinary [3H]TC doubled. When BR was inhibited by feeding calcium supplements or administration of dichloromethylenebisphosphonate, [3H]TC excretion dropped by two-thirds. Thyroparathyroidectomy inhibited [3H]TC excretion by one-third. The results obtained with this technique are therefore similar to those obtained with other methods such as 45Ca kinetics. The effect of dietary manipulations on BR was detected within 6 h of changing diet. Furthermore, a strong diet-dependent but PTH- and calcitonin-independent diurnal rhythm in BR was found. By use of this technique, bone resorption can be assessed continuously over long periods, and the acute regulation of bone resorption can be studied for the first time. PMID- 2221136 TI - Fetal endocrine responses to prolonged hypoxemia in sheep. AB - Our aim was to characterize the pattern of release of epinephrine, norepinephrine, arginine vasopressin (AVP), cortisol (hydrocortisone), and prostaglandin E2 (PGE2) into the fetal circulation during prolonged reductions in uterine blood flow (RUBF). In five sheep RUBF was induced for 24 h, whereas in another five sheep (controls) uterine blood flow was not reduced. Fetal arterial oxygen saturation was decreased from 60.5 +/- 3.6 to 20.3 +/- 1.6% after 2 h of RUBF and remained significantly reduced for the entire RUBF period. The incidence of fetal breathing movements (FBM) and fetal arterial pH were reduced from 36.7 +/- 4.5 min/h and 7.36 +/- 0.01 to 4.3 +/- 1.8 min/h and 7.13 +/- 0.02, respectively, after 2 h of RUBF, but both had returned to control levels after 14 h. Fetal plasma AVP and epinephrine concentrations were increased from 4.4 +/- 0.5 pg/ml and 0.19 +/- 0.05 ng/ml to 333.8 +/- 41.5 pg/ml and 1.5 +/- 0.6 ng/ml, respectively, after 2 h and then declined to near control levels after 12 h of RUBF. Fetal plasma norepinephrine and cortisol concentrations were increased from 1.3 +/- 0.4 and 4.0 +/- 2.2 ng/ml to 6.1 +/- 1.8 and 13.5 +/- 4.1 ng/ml, respectively, after 2 h of RUBF, and both remained significantly elevated throughout the remainder of the RUBF period. Fetal plasma PGE2 concentrations progressively increased (from 1.9 +/- 0.4 to 8.8 +/- 1.7 nmol/l at 12 h) as the duration of RUBF increased and were still significantly elevated after 24 h. The time course for the increase in PGE2 during RUBF was very similar to the increases in arterial pH and in the incidence of FBM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221137 TI - Roles of interleukin 1 beta and tumor necrosis factor in lipopolysaccharide fever in rats. AB - The roles of interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF) in lipopolysaccharide (LPS)-induced fever were investigated in the rat. We used antisera against IL-1 beta and TNF to determine whether we could alter the fever by blocking the action of these cytokines. The intravenous injection of antiserum IL-1 beta 3.5 days before the intraperitoneal injection of LPS resulted in a mean fever that was significantly lower than that seen in rats that had been injected with control serum (0.36 +/- 0.11 vs. 0.82 +/- 0.16 degrees C, P = 0.016). The intravenous injection of antiserum against TNF 3.5 days before the intraperitoneal injection of LPS did not block the fever but significantly enhanced it (1.31 +/- 0.16 vs. 0.82 +/- 0.16 degrees C, P = 0.027). These data support the hypotheses that IL-1 beta is responsible for a significant part of LPS fever and that TNF acts as an endogenous antipyretic to limit the magnitude of LPS fever in the rat. PMID- 2221138 TI - Angiotensin and salt appetite of BALB/c mice. AB - The influence of systemic or intracerebroventricular (icv) administration of angiotensin II on the intakes of NaCl solution, water, and food was investigated in BALB/c mice. Systemic administration of angiotensin II had little, if any, influence on these ingestive behaviors. On the other hand, icv infusion of angiotensin II at 70 ng/day increased (P less than 0.05) intakes of NaCl solution and water by the third day of infusion. The amount of NaCl ingested daily during the infusion was two to three times body sodium content. The mean daily water intake increased to 40-60% of body weight. The vast increase in NaCl intake was not secondary to a natriuresis caused by the icv infusion of angiotensin II. The results suggest that angiotensin II has a direct effect on neural systems involved in sodium appetite in this species. PMID- 2221139 TI - Effect of angiotensin-converting enzyme inhibitor on salt appetite and thirst of BALB/c mice. AB - The role of angiotensin II (ANG II) in Na-depletion-induced Na appetite of mice was investigated. Intraperitoneal injection of the angiotensin-converting enzyme inhibitor captopril at 1.7 mg/mouse (high dose) decreased the Na intake of the Na depleted (furosemide-treated) mice by 80-85%. The decrease in Na intake was restored to the initial level by concurrent subcutaneous infusion of ANG II. High dose of captopril also decreased the Na intake of fluid-deprived, Na-depleted mice. High dose of captopril did not alter water intake in any of the four conditions examined, i.e., in fluid-replete, Na-depleted, water-deprived, or fluid-deprived, Na-depleted mice. Low dose of captopril (1.7 microgram/mouse) tended to or significantly enhanced Na intake of Na-depleted mice. Low dose of captopril, however, did not enhance water intake in any of the conditions examined. Both high- and low-dose captopril treatment decreased food intake in water-deprived mice, whether or not the mice were Na depleted as well. The addition of captopril (0.1 or 1.0 mg/ml) to the drinking water did not influence Na or food intake. Water intake was enhanced during treatment with the low but not with the high dose of captopril. The results are consistent with the proposition that ANG II is involved in the Na appetite of Na-depleted mice. ANG II does not appear to have a role in water intake of Na-depleted or water deprived mice, but neural mechanisms in which angiotensin has a role may influence food intake of water-deprived mice. PMID- 2221140 TI - Decreased cerebral sodium concentration and sodium appetite in BALB/c mice. AB - BALB/c mice were allowed free access to water, food, and 0.3 M NaCl. Intracerebroventricular infusion of 0.7 M mannitol in artificial cerebrospinal fluid (CSF) was used to reduce CSF sodium concentration. The infusion was made at 24 microliters/day, which was similar on a body weight basis to the rate that evoked a large increase in sodium appetite in sheep. Reduction of CSF sodium concentration did not increase the voluntary sodium intake of sodium-replete mice or furosemide-treated, sodium-depleted mice. Thus, in contrast to findings in sheep and cattle and similar to the findings in the laboratory rat and wild rabbits, changes in cerebral sodium concentration are apparently not involved in the sodium appetite of mice. PMID- 2221141 TI - Endocrine and fluid-balance responses to amniotic and allantoic fluid loss in sheep. AB - Our aim was to determine fetal and maternal endocrine and fluid-balance responses to prolonged loss of amniotic and allantoic fluids in sheep. In seven sheep, amniotic and allantoic fluids were drained [379.1 +/- 20.1 (SE) ml/day] from 107 to 135.3 +/- 0.6 days of gestation (term: 145 days). The results from these sheep were compared with those from seven control sheep. Maternal water intake, urine production, and urine osmolality were not altered by fluid drainage, nor were fetal and maternal arterial blood gases, pH, or plasma osmolalities. Fluid drainage increased amniotic, but not allantoic, fluid osmolality. Maternal plasma cortisol concentration increased with fluid drainage, but maternal plasma concentrations of prolactin and arginine vasopressin were unchanged. Fluid drainage increased prolactin concentrations in fetal plasma and amniotic fluid, but fetal plasma concentrations of cortisol (hydrocortisone), arginine vasopressin, norepinephrine, and epinephrine were unchanged. Our results show that the fetus is capable of maintaining its plasma osmolality despite prolonged loss of fluid from its amniotic and allantoic sacs and that this is associated with alterations in the production rate and the composition of amniotic fluid. PMID- 2221142 TI - Norepinephrine sensitivity of mesenteric veins in pregnant rats. AB - This study was designed to test the hypothesis that during the course of pregnancy there is a decrease in the venous response to adrenergic stimulation that is characterized by a decrease in venoconstriction to both exogenous norepinephrine (NE) and to transmural electric stimulation of endogenous sympathetic nerves. Capacitance-size mesenteric veins were removed from nonpregnant and early- (7/8 day) and late-pregnant (18/19 and 20/21 day) Sprague Dawley rats and studied in vitro under pressurized conditions. Lumen diameter was measured continuously by a video-electronic method. There was a marked increase in the sensitivity of the veins to exogenous NE stimulation at the end of pregnancy, which was most dramatic at a transmural pressure of 6 compared with 2 mmHg. The increase in exogenous NE sensitivity was associated with a progressive decline in the response to transmural nerve stimulation during pregnancy. Cocaine, an inhibitor of neuronal uptake, resulted in a greater potentiation of the response to transmural nerve stimulation in the pregnant rats compared to controls, suggesting an increased reuptake mechanism during pregnancy. Additional studies in the pseudopregnant, lactating, and nonlactating rat suggested that the conceptus was necessary for the alterations in neural response but not for the increase in exogenous NE sensitivity. In conclusion there is a dramatic change in venous function during pregnancy in the rat that is characterized by a difference between endogenous and exogenous NE sensitivity. The fact that transmural pressure can profoundly affect exogenous NE sensitivity suggests that pregnancy induced changes in venous volume could contribute to changes in venous reactivity. PMID- 2221143 TI - Testosterone influences hibernation in golden-mantled ground squirrels. AB - At different phases of the hibernation season, castrated male golden-mantled ground squirrels were implanted with capsules that either were filled with testosterone (T) or left empty (blank). Blank-treated animals hibernated normally when housed at 5 degrees C. Entry into hibernation was prevented in the majority of squirrels treated with T several days before the initial cold challenge. T concentrations that inhibited torpor (greater than 1.2 ng/ml) were comparable with those of intact males at the end of the hibernation season. In some squirrels, moderate T concentrations were compatible with hibernation, but torpor bout duration was shorter than normal. The inhibitory effect of T on hibernation did not appear to require aromatization of T to estradiol. We suggest that a steroid-independent mechanism triggers arousal from hibernation and that T dependent processes determine whether hibernation is resumed at the end of an arousal period. PMID- 2221144 TI - Effect of outflow pressure on liver lymph flow in unanesthetized sheep. AB - We used lymph flow rate (QL) to lymphatic vessel outflow pressure (Po) relationships to analyze lymphatic flow in five unanesthetized sheep with liver lymphatic cannulas. The olecranon was the zero reference level for pressures. Increases in Po did not change QL until Po exceeded 19 +/- 4 (SD) cmH2O. However, for Po greater than 19 +/- 4 cmH2O, QL decreased linearly with increases in Po. We fit regression lines to the QL vs. Po data for Po greater than 19 cmH2O and estimated the effective lymphatic resistance (RL) as -delta Po/delta QL. The effective pressure driving lymph (PL) was the Po at which QL = 0. At baseline, RL = 0.18 +/- 0.10 cmH2O.min.microliter-1 and PL = 29.6 +/- 3.4 cmH2O. When we increased hepatic vein pressure by 5.7 +/- 1.7 cmH2O, QL increased to 6.2 +/- 3.2 times baseline, RL decreased to 0.050 +/- 0.015 cmH2O.min.microliter-1, and PL increased to 37.1 +/- 3.5 cmH2O (P less than 0.05). Thus 1) liver lymph flow is very sensitive to increases in hepatic vein pressure, 2) there is a substantial QL vs. Po plateau for liver lymphatics, and 3) after hepatic venous pressure elevations, liver lymph flow increases as if it were driven by a higher pressure through a lower resistance. PMID- 2221145 TI - Functional recovery of the gustatory system after sodium deprivation during development: how much sodium and where. AB - Restriction of maternal dietary sodium beginning on or before embryonic day 8 and continued thereafter results in reduced taste responses of the chorda tympani nerve to NaCl in the offspring. The effects of deprivation, however, are reversible. A single ingestive bout of 30 ml isotonic NaCl was sufficient to restore normal sodium taste, and the restorative effects of the single exposure apparently persisted throughout multiple generations of taste receptor cells. Furthermore, the recovery apparently did not depend on direct receptor cell stimulus interactions. Rats permitted to drink 30 ml of isotonic NaCl, but not allowed to retain it, did not recover normal sodium taste responses, suggesting that factors other than taste stimulation are important in the restorative effects of sodium. PMID- 2221146 TI - Baroreflex responses to acute changes in blood volume in humans. AB - To test the hypothesis that acute changes in plasma volume affect the stimulus response relations of high- and low-pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baroreflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus-response relation of the carotid cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationships of the cardiopulmonary baroreflex were studied by measurements of forearm vascular resistance (FVR) and peripheral venous pressure (PVP) during low levels of lower body negative pressure (0 to -20 mmHg). Altered vascular volume had no effect on response relations of the carotid-cardiac baroreflex but did alter the gain of the cardiopulmonary baroreflex (-7.93 +/- 1.73, -4.36 +/- 1.38, and -2.56 +/- 1.59 peripheral resistance units/mmHg for hypovolemic, normovolemic, and hypervolemic, respectively) independent of shifts in baseline FVR and PVP. These results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulmonary baroreflex but may not be an effective countermeasure against potential post-flight impairment of the carotid-cardiac baroreflex. PMID- 2221147 TI - Preoptic area injection of corticotropin-releasing hormone stimulates sympathetic activity. AB - To investigate the sites of action of corticotropin-releasing hormone (CRH) on sympathetic nerve activity to interscapular brown adipose tissue (IBAT), we injected CRH into the third cerebroventricle, medial preoptic area (MPOA), and other hypothalamic areas in anesthetized rats. The multiunit discharges of sympathetic nerves to IBAT were recorded electrophysiologically. The intracerebroventricular injection of CRH increased sympathetic nerve activity in a dose-dependent manner over the range 250-1,000 pmol. The microinjection of CRH (200 pmol) into the unilateral MPOA increased the sympathetic nerve activity to IBAT by +150.6 +/- 25.9% at 30 min after injection. However, the injection of saline (0.15 M NaCl) and glucagon (200 pmol) into the MPOA did not increase sympathetic nerve activity. The microinjection of CRH (200 pmol) into the anterior hypothalamic area, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, and lateral hypothalamic area had no significant effect on nerve activity. We conclude that central administration of CRH increases the sympathetic nerve activity to IBAT and that the MPOA is one of the sites for this action. The result is consistent with the hypothesis that CRH is a neurochemical stimulator of the sympathetic nervous system, which may be involved in control of energy expenditure in rodents. PMID- 2221148 TI - Calorimetric study of the energetics of pregnancy in golden hamsters. AB - The energetics of pregnancy have been assessed in the golden hamster, using continuous whole body indirect calorimetry to determine energy expenditure throughout gestation. Energy intake was unchanged during pregnancy, either on a daily or cumulative basis. The total energy expenditure per animal was, however, significantly higher (14%) in pregnant hamsters than in virgin control animals. The increase in total expenditure was the result of increases in daily energy expenditure over the last one-third of gestation (mean increase 21%), the period during which the energy costs associated with fetal growth are highest. The respiratory quotient (RQ) of the control hamsters was approximately 0.95, but in the pregnant group there was a progressive reduction over the second half of gestation, and by parturition the RQ had fallen to 0.80. The changes in RQ indicate that there is a switch toward the oxidation of fat, away from the oxidation of carbohydrate, in the later stages of pregnancy. Measurements of body lipid suggest that the fall in RQ in the second half of pregnancy is the result of a net utilization of maternal fat reserves; 42% of maternal body lipid was lost during pregnancy, with most of the loss occurring over the final one-third of gestation. Because energy expenditure is increased (relative to virgin controls) without any change in energy intake, it is evident that the efficiency of energy utilization (energy gain per unit of energy intake) is not increased during pregnancy in the golden hamster. PMID- 2221150 TI - Dissociative analysis of ventromedial hypothalamic obesity syndrome. AB - Electrolytic lesions of the ventromedial hypothalamus (VMH) produce an obesity syndrome characterized by hyperphagia, adiposity, and heightened parasympathetic tone. Experiments were conducted to evaluate the possibility that these symptoms arise from damage to distinct and separated loci within the hypothalamus. Rats received either VMH lesions, perifornical hypothalamic (PFH) knife cuts, ventromedial hypothalamic nucleus (VMN) lesions, or sham surgery (Sham). When maintained ad libitum, VMH and PFH rats were hyperphagic, overweight, and became obese. VMN rats were not hyperphagic, nor did they gain excessive weight, but they did develop an obesity reflected as a significantly elevated level of carcass fat. Under restricted feeding conditions, both VMH and VMN rats became obese; PFH rats did not. Also, only VMH lesions and PFH knife cuts increased basal gastric acid secretion. These data demonstrate dissociations between hyperphagia and obesity, as well as between stomach secretion and obesity, in the VMH syndrome. The implications of these findings for a dissociative model of the VMH obesity syndrome are discussed. PMID- 2221149 TI - Insulin modifies flavor aversions and preferences in real- and sham-feeding rats. AB - In separate, parallel experiments, rats were allowed to sham or real feed a flavored sweetened condensed-milk solution after a 17.5-h fast. Coinciding with administration of the milk were injections of insulin or vehicle (saline). Insulin had no effect on intake in the real feeding situation, and flavors paired with insulin (0.8, 2.5, or 5.0 U/rat) were avoided, relative to saline-paired flavors. In sham-feeding rats, insulin (0.8 U/rat) significantly reduced the amount of milk consumed, and flavors paired with insulin injection were preferred, relative to saline-paired ones. Insulin produced a relatively larger hypoglycemia during sham feeding than during real feeding. Thus it appears that insulin-paired flavors of milk may be preferred by animals when they are ingested in sham feeding but not in animals real feeding. Perhaps rapid gastric emptying, as would occur with a liquid diet, accompanied by increased insulin levels, leads to malaise and flavor aversion. PMID- 2221151 TI - Control of ventilation in adult rats hypoxic in the neonatal period. AB - Three groups of 50-day-old (i.e., postpuberty) rats have been studied: controls, rats exposed to 6 days of hypoxia [inspired fraction of O2 (FIo2) = 10% O2] when newborn (Nb-Hypox), and rats exposed to the same level and duration of hypoxia after weaning (Ad-Hypox). Ventilation during normoxic breathing was higher in Nb Hypox than in controls or Ad-Hypox. The ventilatory response to acute hypoxia (10 min of 10% O2) was about one-half in Nb-Hypox than in the other two groups. Additional measurements performed on Nb-Hypox and controls showed minimal or no differences between the two groups in the ventilatory responses to hyperoxia and hypercapnia, heart rate and blood pressure at various FIO2, and blood biochemistry. Analysis of the Hering-Breuer reflexes, during barbiturate anesthesia, suggested a decreased central inhibition on inspiratory activity in Nb-Hypox, which with a lower sensitivity to inputs from the peripheral chemoreceptors may contribute to the normoxic hyperventilation and the blunted response to acute hypoxia. The ventilatory patterns of Nb-Hypox rats bear numerous similarities with those of high-altitude natives and could suggest that the highlander's ventilatory responses are not genetic characteristics but relate to chronic hypoxia early in life. PMID- 2221152 TI - Diminished cardiovascular responsiveness to vagal stimulation in obese rats. AB - Obese rats maintained on a high-fat diet since weaning were studied to determine whether parasympathetic deficiencies contribute to the cardiovascular malfunction in obesity. Elevations in tail-cuff systolic pressures and plasma insulin indicated that obese rats had borderline hypertension and hyperinsulinemia. Reflex bradycardia produced by angiotensin or phenylephrine in conscious obese rats was less than that in age-matched controls. However, reflex responses elicited by phenylephrine or sodium nitroprusside when the same rats were later anesthetized did not differ between groups. Impairment of afferent or central components of the baroreflex arc was considered unlikely, because depressor, bradycardic, and sympathoinhibitory responses to electrical stimulation of aortic depressor afferents were similar in both rat groups. By contrast, efferent parasympathetic mediation was probably reduced, since depressor and bradycardic responses to electrical stimulation of vagal nerve efferents were significantly smaller in obese than in control rats. Collectively our findings suggest that cardiovascular and baroreflex malfunction in obese rats may result from an autonomic imbalance involving diminished parasympathetic activity. PMID- 2221153 TI - Responses of harbor seal and pig heart to progressive and acute hypoxia. AB - Myocardial oxidative and glycolytic reserves were evaluated in four harbor seals, Phoca vitulina richardsi, and six domestic pigs, Sus scrofa (hematocrits: 58 +/- 5 and 34 +/- 1%., respectively). Progressive hypoxia was induced by lowering arterial hemoglobin-oxygen saturation in 10% decrements, each maintained for 10 min periods, until the onset of heart failure. Myocardial oxygen consumption rate (VO2), lactate release/uptake rate (L), and triple product, an index of myocardial energetic demand, were determined at each saturation level. Onset of L began in pigs at Sao2 = 57 +/- 5% and in seals at Sao2 = 35 +/- 4%. Cumulative oxygen consumption (VO2) during hypoxia, determined from the onset of cardiac lactate release, was 435 ml O2/100 g in seals and 172 ml O2/100 g in pigs. Cumulative lactate release during the same period was 14 mM/100 g in seals and 4.6 mM/100 g in pigs. The pigs' left ventricular contractile response (dP/dtmax) was greater than that of seals throughout the time of lactate release. Total myocardial energetic sources were higher in seals than in pigs, and seals were better able to tolerate myocardial hypoxia than were pigs. In a separate experiment, two seals and six pigs were made acutely hypoxic until cessation of cardiac output (seals, 17.5 min; pigs, 7.4 min) and were then reoxygenated. Both seals recovered promptly to control levels of cardiac mechanical function, whereas none of the pigs recovered. Additionally, five pigs were beta-blocked with 0.10 mg/kg of propranolol and were subjected to acute hypoxia. Tolerance to cardiac hypoxia in beta-blocked pigs was significantly increased compared with that of control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221154 TI - DSM-IV: work in progress. AB - The authors present an overview of the work in progress on DSM-IV. After a brief historical review, they discuss the principles and multiple purposes of the DSM IV effort and outline the three stages of its empirical documentation: systematic literature reviews, analysis of unpublished data, and field trials. Next, they discuss several of the basic conceptual issues that are implicit in revising a nomenclature. These include the definition of mental disorder, the balance between multiple diagnosis and differential diagnosis, the use of categorical and dimensional models of classification, and issues involved in the construction of criteria. Finally, they summarize the most important specific questions being reviewed by each of the DSM-IV work groups. PMID- 2221155 TI - A critical review of epidemiological studies of Puerto Rican mental health. AB - Through a review of the epidemiological literature on the mental health of Puerto Ricans and other Hispanics, the authors argue that lack of attention to cultural issues in epidemiological studies leaves many questions unanswered and raises concerns about the validity of studies in this area. The authors point out that the mental health status of Puerto Ricans in New York City is still poorly understood after 30 years of research. The roles of cultural response styles and of culturally meaningful expressions of distress in shaping responses to research interviews should be central concerns in developing research in cross-cultural psychiatry. PMID- 2221156 TI - Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. AB - Recent neuropathologic investigations in schizophrenia report smaller volume of medial temporal lobe structures. These findings are confirmed by preliminary magnetic resonance imaging (MRI) studies. Direct stimulation of lateral temporal lobe structures in the region of the superior temporal gyrus provokes hallucinations. The authors' MRI study of young schizophrenic patients demonstrates smaller volume of the superior temporal gyrus (an auditory association area) and of the left amygdala. Smaller size of the left superior temporal gyrus and left amygdala is not accounted for by smaller size of the overall brain or temporal lobe. Shrinkage of the left superior temporal gyrus is strongly and selectively correlated with severity of auditory hallucinations. PMID- 2221157 TI - Plasma norepinephrine in chronic schizophrenia. AB - Several lines of evidence indicate altered noradrenergic function in schizophrenia. The authors examined resting, standing, and change (standing minus resting) in plasma norepinephrine levels in 14 drug-free patients with chronic schizophrenia or schizoaffective disorder and in 33 age- and sex-matched healthy volunteers. Schizophrenic patients had significantly higher resting and standing plasma norepinephrine levels and significantly greater change. Resting and standing levels were significantly related to positive and negative symptoms. There was a significant positive correlation between resting plasma and CSF norepinephrine levels and a significant negative correlation between CSF homovanillic acid and resting, standing, and change in plasma norepinephrine levels. PMID- 2221158 TI - Influence of patient-related variables on clozapine plasma levels. AB - The authors investigated the clozapine plasma levels of 148 psychiatric inpatients. Multiple regression analysis revealed a linear relationship between dose of clozapine and plasma concentrations. The analysis showed a significant influence of dose, sex, smoking, weight, and age on the plasma concentrations of clozapine under clinical conditions. These results remained significant when clozapine doses below 150 mg/day and above 500 mg/day were excluded from the analysis. PMID- 2221159 TI - Personality differences between patients with remitted melancholic and nonmelancholic depression. AB - Seventy-five patients with remitted depression were categorized as having melancholic-endogenous or non-melancholic-nonendogenous depression according to DSM-III criteria, Research Diagnostic Criteria, and the Newcastle endogeneity scale. The patients' scores on four personality scales--the Eysenck Personality Inventory, the Interpersonal Dependency Inventory, locus of control, and the Interpersonal Sensitivity Measure--were then compared. Patients with nonmelancholic-nonendogenous depression were generally rated as having more vulnerable personality styles, but the differences were dependent on the particular diagnostic system used. A principal components analysis isolated three underlying personality constructs--dependency, introversion, and timidity. Patients with nonmelancholic-nonendogenous depression scored as significantly more dependent. PMID- 2221160 TI - Depression in dementia of the Alzheimer type and in multi-infarct dementia. AB - The authors used the Hamilton Rating Scale for Depression and a rating of depressed mood to investigate the prevalence of depression in 55 patients with Alzheimer's disease, 37 patients with multi-infarct dementia, and 30 nondemented comparison subjects. The prevalence of depressed mood depended on the severity of dementia as measured by the Mini-Mental State examination and was significantly lower among patients in more severe stages of Alzheimer's disease but not among patients with severe multi-infarct dementia. PMID- 2221161 TI - Value of the DST for predicting response of patients with major depression to hospitalization and desipramine. AB - The authors examined the value of the dexamethasone suppression test (DST) for predicting response of patients with unipolar, nonpsychotic major depression to 1 week of hospitalization without antidepressant drugs and to a 4-week trial of desipramine at a fixed plasma level. The rates of response to hospitalization without drug treatment (defined as a score of 12 or less on the Hamilton Rating Scale for Depression) were not significantly different for the patients with a positive DST and those with a negative DST. This finding differs from those of prior studies of the DST and response to placebo. The responses of the DST positive and DST-negative patients to desipramine also did not differ, a finding that replicates those in some prior reports. PMID- 2221162 TI - Antidepressant pharmacotherapy of depression associated with multiple sclerosis. AB - In a double-blind clinical trial involving 28 patients with multiple sclerosis and major depressive disorder, 14 patients were randomly assigned to a 5-week trial of desipramine and individual psychotherapy and 14 to placebo plus psychotherapy. Clinical judgments indicated that patients treated with desipramine improved significantly more than the placebo group. This was confirmed by scores on the Hamilton Rating Scale for Depression but not by Beck Depression Inventory scores. Side effects limited desipramine dosage in half of the treated patients. The authors conclude that desipramine has a modest beneficial effect in serious depression associated with multiple sclerosis but that side effects may be more of a limiting factor than in patients without medical or neurologic disease. PMID- 2221163 TI - Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey. AB - Follow-up studies of psychiatric patients with panic disorder have shown an abnormally high mortality rate in men due to cardiovascular and cerebrovascular events. The authors report that in the New Haven portion of the Epidemiologic Catchment Area program the risk for stroke in persons with lifetime diagnoses of panic disorder was over twice that in persons with other psychiatric disorders or no psychiatric disorder. After adjustments for demographic differences between groups, the risk was even higher. While the results should be interpreted cautiously because of the small sample and absence of medical examinations, these findings are consistent with clinical studies showing an association between panic disorder and cardiovascular/cerebrovascular events. PMID- 2221164 TI - Successful treatment of nonpurging bulimia nervosa with desipramine: a double blind, placebo-controlled study. AB - Twenty-three women with nonpurging bulimia underwent a 12-week, double-blind, placebo-controlled trial of desipramine hydrochloride. Repeated standardized rating scales, mood assessments, and self-reports of dietary habits were used to measure changes in binge frequency and cognitive processes associated with food intake. The women who received desipramine reduced their frequency of binge eating by 63%, but women receiving placebo increased their frequency of binge eating by 16%. Twelve weeks after initiating treatment, 60% of the treatment group but only 15% of the placebo group abstained from binge eating. The women who received desipramine showed significantly more dietary restraint and reported significantly less hunger, suggesting that desipramine acts to suppress appetite. These preliminary findings suggest that the therapeutic effects of desipramine established in the treatment of purging bulimia nervosa extend to patients with nonpurging bulimia. PMID- 2221165 TI - Update on the epidemiology of anorexia nervosa in a defined region of Switzerland. AB - In this follow-up investigation, the authors studied all Swiss women in the canton of Zurich who developed anorexia nervosa between ages 12 and 25 years and who were hospitalized for the first time with this diagnosis between 1983 and 1985. Data were compared with those from an earlier study, which focused on the periods 1956-1958, 1963-1965, and 1973-1975. The incidence of anorexia nervosa did not increase significantly during 1983-1985 compared to 1973-1975, in contrast to the constant increase found between 1956 and 1975. However, the more frequent use of vomiting and abuse of laxatives in 1983-1985 may indicate an increase in cases with mixed features of anorexia nervosa and bulimia. PMID- 2221167 TI - Structured interviews for borderline personality disorder. AB - The authors compared three instruments used to diagnose borderline personality disorder--the Diagnostic Interview for Borderline Patients (DIB), the Schedule for Interviewing Borderlines, and the Structured Interview for DSM-III Personality Disorders--in 56 patients with personality disorders. A borderline diagnosis was made according to the DIB in 30%, the Structured Interview for DSM III Personality Disorders in 48%, and the Schedule for Interviewing Borderlines in 55% of the patients. Diagnostic agreement was only 52%, which has implications for the generalizability of results of validation studies of the borderline diagnosis. Improvement in diagnostic agreement requires modification of current criteria sets and/or the use of dimensional models. PMID- 2221166 TI - Thyroid function and ultrasonically determined thyroid size in patients receiving long-term lithium treatment. AB - Thyroid function was investigated in 100 manic-depressive patients. Goiter was more common in patients treated with lithium for 1-5 years (44%) or more than 10 years (50%) than in patients who never received lithium (16%). Smoking contributed significantly to thyroid size and goiter. In nonsmoking patients, ultrasonically determined thyroid volume was significantly related to treatment duration. The mechanism behind this increased thyroid volume is unclear, as most patients had normal serum thyrotropin levels and no thyroid autoimmunity. Subclinical or overt hypothyroidism was found in 4% and 21% of patients treated for 1-5 and more than 10 years, respectively. Since few hypothyroid patients had autoimmunity or goiter, lithium may affect the thyroid gland directly. PMID- 2221168 TI - Children's PTSD reactions one year after a sniper attack at their school. AB - Fourteen months after a sniper attack at an elementary school, level of exposure to that event remained the primary predictor of ongoing posttraumatic stress reactions in 100 schoolchildren who were followed up. Guilt feelings and knowing the child who was killed were associated with a greater number of symptoms. Grief reactions occurred independent of degree of exposure to the event. The authors discuss the public health implications of these longitudinal findings. PMID- 2221169 TI - Psychiatric status of adolescents who had extreme temperaments at age 7. AB - Two temperamentally extreme (extremely easy and extremely difficult) subgroups of children were selected at the age of 7 years from a large random sample of the general population of Quebec City. The clinical status, family functioning, IQ, and academic performance of these children were reassessed at 12 and 16 years of age. Findings suggest that extreme temperament at age 7 predicts psychiatric status in preadolescence and adolescence only when family functioning is also taken into account. The adolescents who had been temperamentally difficult children and who were living in families with dysfunctional behavior control displayed more clinical disorders. PMID- 2221171 TI - Cocaine/"crack" dependence among psychiatric inpatients. AB - The authors studied 40 cocaine-dependent subjects admitted to psychiatric inpatient wards of a metropolitan hospital because of general psychiatric symptoms. The results indicate that the predominant form of cocaine administration (88%) was freebasing "crack." DSM-III-R cluster B personality disorders (N = 17) and schizophrenia (N = 13) constituted the diagnoses for 75% of the sample. Compared to the schizophrenic patients in this cohort, the patients with cluster B personality disorders used cocaine in greater quantities and more frequently and began abuse of the drug at an earlier age. The escalation in urban areas of psychiatric hospitalizations attributed to use of crack may be largely related to psychiatric symptoms in cocaine-dependent patients with personality disorders as well as cocaine-induced psychopathology in schizophrenic patients. PMID- 2221170 TI - The natural history of alcohol abuse: implications for definitions of alcohol use disorders. AB - Is the DSM-III-R category of alcohol abuse validly differentiated from the DSM III-R category of alcohol dependence, or is abuse primarily a mild, prodromal condition that typically deteriorates into dependence? A 4-year longitudinal epidemiologic study of male drinkers provided data to answer this question. The study used identical questions at baseline and follow-up. At follow-up, 70% of the subjects who were initially classified as alcohol abusers were still abusers or were classified as remitted. This contrasted significantly with outcome in the subjects who initially reported alcohol dependence. Although additional research is needed, these results indicate that alcohol abuse often has a course distinct from that of alcohol dependence. PMID- 2221172 TI - Dissociative experiences in the general population. AB - The Dissociative Experiences Scale was administered to a random sample of 1,055 adults in the city of Winnipeg. Results showed that scale scores did not differ between men and women and were not influenced by income, employment status, education, place of birth, religious affiliation, or number of persons in the respondent's household. Dissociative experiences are common in the general population and decline with age. The findings suggest that dissociative disorders may also be common in the general population. PMID- 2221173 TI - Psychiatry takes to the streets: the New York City initiative for the homeless mentally ill. AB - The authors describe New York City's program to remove seriously mentally ill homeless people from the streets to a public hospital. They report on the 298 patients hospitalized during the first year of this program. Most of the patients were male (66%), single (77%), and from outside of New York City (79%) and claimed a history of previous psychiatric hospitalization (92%) and that they had been homeless for more than 1 year (66%). Most of the patients suffered from schizophrenia (80%) and had additional medical diagnoses (73%). Follow-up contact with the patients 2 years after initiation of the program revealed that 55% of the patients either were living in a community setting or were under institutional care. PMID- 2221174 TI - Antidepressant-induced mania. PMID- 2221175 TI - Transient SIADH associated with fluoxetine. PMID- 2221176 TI - Discussion of fluoxetine and suicidal tendencies. PMID- 2221177 TI - Another case of self-cutting after combat stress. PMID- 2221178 TI - Obsession or worry? PMID- 2221179 TI - Comment on DSM-III-R panic disorder with agoraphobia. PMID- 2221180 TI - Seasonal independence of decreased intraocular pressure dynamics in seasonally depressed women. PMID- 2221181 TI - Initial reaction and subsequent response to antidepressants in panic patients. PMID- 2221182 TI - Manic illness presenting with physical symptoms. PMID- 2221183 TI - Use of unproven and unapproved drugs to treat cocaine addiction. PMID- 2221184 TI - Decisions in psychopharmacologic treatment. PMID- 2221185 TI - Hopelessness as a predictor of suicide. PMID- 2221186 TI - Personality traits and ethnic background. PMID- 2221187 TI - Seasonal variation in bulimic symptoms. PMID- 2221189 TI - More on psychotherapy training during residency. PMID- 2221188 TI - Further discussion of article on prodromal symptoms in panic disorder. PMID- 2221191 TI - The psychiatrist and the juvenile justice system. PMID- 2221190 TI - Comments on review of Male homosexuality. PMID- 2221192 TI - Identification of letters in the predesignated target paradigm: a word superiority effect for the common word the. AB - The size of the perceptual unit used in reading was addressed using the predesignated target paradigm. Sixteen subjects viewed the following stimuli in random order: the words tee, the, tie, and toe; the nonwords eet, eht, eit, and eot; and the letters e, h, i, and o. Subjects fixated on the location of the center letter and identified the letter as e, h, i, or o, alternatives which were known to them at the onset. A word superiority effect was obtained for the common word the but not for the less common words tee, tie, and toe. The word superiority effect was attributable to bias rather than discriminability: Subjects exhibited a bias to perceive the words in this experiment as the (i.e., there was a bias to perceive h in the t e stimulus presentations). These results suggest that the common word the is processed in reading units that are larger than the letter, and that the system is biased to perceive common rather than uncommon words in data-limited conditions. PMID- 2221193 TI - Memory for names and faces: a fair comparison. AB - Comparison between recognition memory for materials drawn from different stimulus classes has been hazardous because of unavoidable variation in the similarity of director sets involved. The present study attempts to make a more equitable comparison between memory for names and faces by employing both distractor-free and conventional recognition tests. University undergraduates viewed slides of names or faces and subsequently attempted to identify those they had seen earlier. The interaction between stimulus class and type of recognition test was significant. It is suggested that the frequently reported superiority of memory for faces as compared with names may be an artifact of the distractors used in these tests. PMID- 2221194 TI - Effect of instructions on elementary cognitive tasks sensitive to individual differences. AB - The effect of instructions on basic cognitive tasks was investigated. In the first study, 60 college students completed both a choice reaction time and a modified match-to-sample task. Students were given either written, non-verbal, or no instructions. Mean level of performance changed across type of instruction for each task. The correlations between the task parameters and a measure of general intelligence also appeared to change across instructional conditions. A second study was conducted with 464 Air Force and National Guard recruits who completed choice reaction time, match-to-sample, tachistoscopic threshold, and probed recall tasks. Approximately half of these subjects received standard written instructions while the others received no instructions. Mean group differences were substantial but decreased with practice. Patterns of individual differences between the instruction and no-instruction conditions varied more with increased task complexity, with greater change occurring in more complex tasks such as probed recall. In sum, instructions have a significant impact on mean performance on basic cognitive tasks and a lesser effect on individual differences. PMID- 2221195 TI - Cultivating openness in the therapeutic relationship. PMID- 2221196 TI - The bipolar causality of regression. PMID- 2221197 TI - Culture and symptomatology--the role of personal meaning in diagnosis and treatment: a case study. PMID- 2221198 TI - The collective past, group psychology and personal narrative: shaping Jewish identity by memoirs of the Holocaust. AB - Through honing its collective memory, especially after the Holocaust, the Jewish community has attempted to sustain its culture, bolster the Jewish identity of its members, and regain a resolute sense that its narrative is again proceeding. To some degree, all these aims are realized by instilling in its members the Jewish modal character structure: a psychological configuration with two contrastable entities. One chronically discomposed self-structure, defining itself as polluted and helpless, trembles with the appalling imagery of historical and imminent community disasters. The other entity believes in its unmatched capacity for reparative, socially beneficial actions. The paradigm of this psychological organization is found in many children of survivors. The memory of a tragic history abides alongside the community's hopes in the Jewish modal personality. The need to set forth and accommodate these two motifs imprints upon the Jewish "national" character many of its distinctive qualities. The designs of the Jewish community for this particularly Jewish twofold personality formation are augmented by the personal revelations of survivors. Therefore, Holocaustic testimonies are invested with a sacred aura. In measure, these recitals of the disaster with their stark images, plus the clashing affects aroused in the reader toward main characters of the narrative, dictate the way Jews define themselves in the world and the way they live. A confluence of being covertly commissioned by the Jewish community joins with the narrators' more idiosyncratic longings. Together they generate a steady stream of Holocaustic accounts. Complementary vectors drive the reader to peruse these records. The results therefrom, intimate knowledge of the disaster, plus the twofold personality motifs stamp many Jews as scions of the Holocaust. PMID- 2221199 TI - Love and fellowship in the doctor-patient relationship in psychiatry. PMID- 2221200 TI - Abusive families and character formation. AB - Family research studies confirm that abusive parents tend to be undifferentiated partners who compete with each other and with their children for attention and nurturance. More or less healthy parents make demands on children to counteract their own injured narcissism, but they do so largely without devaluation and the sadistic use of projective identification. Under sufficient stress abusive parents attack the child who fails to gratify their needs, thereby giving vent to longstanding frustrations and feelings of being threatened by the child's individuation and competency. The emotional atmosphere in such families facilitates ego deficits like those of the borderline personality as it molds the child's efforts to avoid anxiety. Devaluation, loss, and defenses against mourning partially account for depression and paranoid traits in abused youngsters. Early neglect and abuse exposes them to influential models who act out rage and primitive defenses. Some abused individuals project their rage and later become paranoid or antisocial, whereas others fragment or retain infantile defenses. The destructiveness of severe psychological abuse lies in the constriction of the experiencing self and healthy character development, together with the conditioning to repeat abusive relationships and to avoid intimacy. Achieving individuation under these circumstances entails overcoming the internalized abusive relationships and relinquishing the unconscious wish to be transformed from the abused into the abuser. PMID- 2221201 TI - The single parent: power and the integrity of parenting. AB - I have explored some issues of power and the balance of power in the situation of the single parent and the family. The single parent may need the support of a holding environment to achieve psychological integration as exemplified by my treatment with Ms. B. Without a cooperative mate and with societal prejudice, the psychotherapeutic situation may be the only nurturing environment. The therapist empowers the single parent by providing a supportive, nurturing environment. Parenting is receiving bad press in this decade. More examples of child abuse and the extreme of homicide come to public attention. Children do have power and society needs to support a constructive use of child as well as parental power. At this stage in societal/cultural development the legal system is unfortunately more available to punish than provide lines of protection or guidance to parent or child. The psychoanalytic literature hasn't been kind or supportive to the parent. We must keep in mind that the psychotherapist's lot is simpler, less stressful, and more protected from real life stresses than that of the single parent. I suggest a model of parenting with the establishment of ongoing dialogue between parent and child in which each is receptive to the other. While it is the parental task to set limits and teach about the real world, the goal is to establish an exchange in which parent and child are both teacher and student. This creative relationship produces growth and builds esteem for parent and child alike. PMID- 2221202 TI - Was Freud really tone deaf? A brief commentary. PMID- 2221203 TI - Out of despair. PMID- 2221204 TI - The relationship between socioeconomic and sociopolitical forces and individual psychologic behavior in Central and Eastern Europe: a proposed international study. PMID- 2221205 TI - The psychotherapies in the context of new developments in the neurosciences and biological psychiatry. AB - We are in an era when the common denominators accounting for the major favorable effects of the different psychotherapies merit further clarification. At the same time, definite progress has been made in determining those specific psychotherapeutic techniques and methods that produce the desired results most efficiently with particular types of patients with specific types of problems. Continuing psychotherapy research will be required, and such research will need to be linked and co-ordinated with the new scientific progress being made in biological psychiatry and the neurosciences. PMID- 2221206 TI - Relationship between hypochondriasis and obsessive-compulsive personality disorder: close relatives separated by nosological schemes? AB - It has been proposed that the relationship between obsessive-compulsive personality disorder and hypochondriasis can basically be conceptualized along the severity continuum, so that hypochondriasis would be conceived of as a more pervasive and more incapacitating form of the same or closely related underlying psychopathology. Clinically, this relationship is manifested through emergence of hypochondriasis as a complication of the obsessive-compulsive personality disorder. The principal components of the psychopathology common to both disorders, are perception of excessive threat to oneself with the consequent experience of vulnerability and insecurity, mistrust in oneself and others, greatly increased need for control, inordinate search for security, poor tolerance and fear of uncertainty and ambiguity, and specific cognitive style, mainly developed to support a struggle for control. In view of the most striking phenomenological characteristic of both disorders being an excessive need for control, displayed in a repetitious manner, the essence of hypochondriasis and obsessive-compulsive personality disorder could be captured by the term "chronic disorders of the measure of control." The main phenomenological differences between hypochondriasis and obsessive-compulsive personality disorder have been interpreted as expressive of the lower and higher levels of intrapsychic integration respectively. In this regard, the manner in which the bodily self has been formed and the degree to which it has been incorporated into the self as a whole have been considered particularly important. PMID- 2221207 TI - Twelve cognitive errors about multiple personality disorder. AB - Multiple personality disorder (MPD) is often responded to with extreme skepticism by mental health professionals. This skepticism is based in part on twelve cognitive errors about the disorder that can be corrected by argument and research evidence. The errors include the mistaken ideas that MPD patients have more than one personality; that the diagnosis means such patients are not responsible for their actions; that MPD patients are really just borderlines; that MPD is an iatrogenic artifact; that MPD can be created experimentally; that MPD must be rare; that MPD is a therapeutic metaphor; that everyone has different personalities; that MPD will go away if you ignore it; that patients pretend to have MPD in order to please the therapist; that the abuse histories of MPD patients are confabulated; and that one must be a hypnotist to treat MPD. It is important to correct these cognitive errors because MPD is not rare. It can be diagnosed with good reliability and its features are stable and consistent in a number of large published series. Although definitive treatment-outcome studies have not been conducted, clinical experience to date suggests that the disorder can often be cured with psychotherapy. After successful integration, MPD patients function much better than before, and can be released from the mental health system. PMID- 2221208 TI - Covert multiple personality underlying eating disorders. AB - Frequently, MPD patients present themselves to the clinician with a variety of psychophysiological symptoms. Eating-disorder symptoms may be one of these, and may include the following: binge eating, self-induced vomiting, laxative abuse, excessive exercising, body image distortion, self-starvation, fluctuations in body weight, and nausea. Following are five cases in whom the pathological eating behavior was a manifestation of an underlying multiple personality disorder. The pathological eating behavior was so severe that some patients matched DSM-III-R diagnostic criteria for an eating disorder. Clinicians dealing with eating disorders should be aware that some patients may represent a subgroup in whom the underlying cause for the eating disorder may be MPD. These patients seldom respond to conventional treatment modalities used in eating-disorders programs, and only when the underlying multiplicity is identified and treated by a trained clinician, will the patient's eating-disorder symptoms improve. PMID- 2221209 TI - Supervising the therapy of patients with eating disorders. AB - Supervising residents, fellows, and interns conducting psychoanalytic psychotherapy with eating-disorder patients presents special problems and opportunities. The authors explore specific countertransference issues in the long-term therapy of patients with anorexia and bulimia, and describe how these issues in the therapy are often mirrored in the supervisory process. Countertransference phenomena include being secretive, intrusive, shaming, overcontrolling, overindulgent, or overidentified. Experiences associated with countertransference impasses include power struggles, despair, helplessness, and boredom. The wide range of transference and countertransference manifestations represents the difficult domain of long-term therapy with anorexic and bulimic patients, whose relationship with their eating symptom is so complex and ambivalent. Therapists in training benefit from a supervisory attitude of respect and empathy, with specific attention to countertransference difficulties as they arise. While unaddressed countertransference poses the risk of disrupting the supervision and/or the therapy, appropriate recognition and exploration of its meaning in the supervision is an especially valuable training tool in the teaching of psychodynamic psychotherapy, and a source of learning for the therapist in training, the supervisor, and ultimately the patient. PMID- 2221210 TI - Combat-related, chronic posttraumatic stress disorder: implications for group therapy intervention. AB - The patient with combat-related chronic Posttraumatic Stress Disorder suffers from a wide spectrum of maladaptive behaviors. This paper delineates the work that has been done with such a population in group therapy. The plan that is proposed takes into account three interrelated sets of factors: factors important for creating an effective working relation; curative factors; and particular themes. Each of these factors is analyzed in the light of the particularities of group work with such a population. Each of the points discussed is based upon the relevant literature, upon the experience of the therapist, and illustrated with examples. PMID- 2221212 TI - Relaxation and merging in the treatment of personality disorders. AB - A behavioral intervention specifically designed to merge split self representations was found helpful as an adjunct to the psychotherapy of personality-disordered patients. The method, which is introduced only after signs of split self-representation have been identified through exploratory psychotherapy, consists of a series of steps. Patients are first taught a relaxation technique and are asked to practice at home. Once they are able to relax in the session, they are asked for visual images of first one and then another of the conflicting self-representations. After clear images have been elicited and discussed, they are encouraged to merge them. Finally, they are asked "Who's watching" or some similar question designed to elicit a statement about a unified self. Twenty-four of 27 patients meeting criteria for personality disorders in Clusters B and C of DSM-III-R responded with greater compliance, reduced resistance, and improved relationships at work and elsewhere. Comparison is made to the merging intervention commonly used in the treatment of Multiple Personality Disorder. PMID- 2221211 TI - Hypnosis: placebo or nonplacebo? AB - According to Grunbaum's definition of placebo, a therapeutic procedure can be considered a nonplacebo if it can be demonstrated that its effects are produced according to the theory upon which the therapy is based. If the theory is adopted that hypnotic effects depend upon mobilization of the patient's hypnotizability, which is a measurable characteristic, a testable theory is provided. Experimental literature is reviewed that shows that placebo effects are not related to hypnotizability. Clinical outcome studies make it clear that results of hypnotherapy are related to hypnotizability in some disorders such as pain and anxiety, but not in the treatment of addiction or habit disorders. An example of a procedure is given in which hypnosis is nonetheless usefully applied for its placebo value as a method to generate positive expectancies. PMID- 2221213 TI - Splitting and projective identification among healthier individuals. AB - This paper illustrates splitting and projective identification among people with normal and neurotic personality organizations. Adding these concepts to the repertoire of analytically oriented psychotherapists does not replace previous theories but adds to them. This approach can be integrated with drive theory and ego psychology in practice, or can be used to supplement the approaches of cognitive or interpersonal therapists. Not only borderline patients, but all of us, continually need to define and re-define ourselves in relation to others as we grow and change. The concepts of splitting and projective identification can help when that growth process becomes stymied. PMID- 2221214 TI - Treating those who fail to take themselves seriously: pathological aspects of humor. AB - A method of analyzing humor was presented. Patients are first made aware of their "being amused" by bringing their smiling and laughing to their attention. They can be then be led to see that their external life situation has predisposed them to experience an intrapsychic event--the spontaneous emergence of antithetical ideation into consciousness which has, in turn, given rise to three beliefs: (1) the ir-responsibility, (2) the incongruity, and (3) the inconsequentiality of the production and nature of this ideation. Two patients were presented to illustrate how foreknowledge of the three beliefs could aid the therapist in working through what might otherwise have been intractable pathology. The author is, generally, in favor of a more relaxed attitude about the use of humor and nonverbal expressive behavior in general, but urges that this material be integrated within the framework of a structured cognitive approach. PMID- 2221215 TI - Adult agoraphobia and childhood separation anxiety: using children's literature to understand the link. AB - Separation-anxiety stories are frequent in children's literature and have eight characteristic elements. Peter Rabbit is used as an early and very simple example. A case study follows which illustrates the fear of separating from the family in an adult agoraphobic. The Wizard of Oz is presented as a more expanded version of a separation-anxiety story. A case study follows which illustrates a woman's difficulty with maturity and separation. A review of the literature is made in which studies are cited which indicate a history of childhood-separation problems in adult agoraphobics. Studies also show that panic disorder in these patients is often precipitated by losses and separations. Studies also show that agoraphobics may have poor problem-solving skills. Children's stories may serve as a guide to children toward mastery of separation fear. A case study follows of a man who developed a panic disorder while watching E.T. E.T. is presented as a separation-anxiety story for the late 1900s. The paper concludes with a brief review of children's separation-anxiety stories and how they reflect broad cultural changes. PMID- 2221216 TI - Mortality and infertility in adult mosquitoes after the ingestion of blood containing ivermectin. AB - Mosquitoes of 3 species (Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus) were fed on human blood containing various concentrations of ivermectin. Three effects (death, decreased egg production, and reduced egg hatching) were observed in the insects, depending upon the concentration of ivermectin ingested. The LD50 of ivermectin in human blood for the 3 mosquito species was estimated to be 126, 208, and 698 ng/ml, respectively. Mosquitoes dying after ingestion of ivermectin developed signs of acute toxicity including paralysis, lethargy, incoordination, and difficulty in movement. Death usually occurred within 48-72 hr. With sublethal blood concentrations of the chemical, mosquitoes survived, but there was a marked reduction in both the number and viability of their eggs. This infertility was only temporary, however, as subsequent refeeding of the insects on uncontaminated blood resulted in the production of normal numbers of fertile eggs. Blood levels of ivermectin which made 50% of the eggs infertile in Ae. aegypti and Ae. albopictus were calculated 3.4 and 4.3 ng/ml, respectively. These latter concentrations of the chemical are within the range found in blood of humans and domestic animals receiving ivermectin for treatment of parasitic infections. This finding suggests that the widespread use of ivermectin in veterinary and human medicine may have an unrecognized effect on mosquito populations. PMID- 2221217 TI - Humoral and cell-mediated immune responses to the Plasmodium falciparum antigens PF155/RESA and CS protein: seasonal variations in a population recently reexposed to endemic malaria. AB - Resurgence of falciparum malaria occurred in the Central Highlands of Madagascar in the 1980s and the disease is currently hyperendemic. We determined the humoral and cellular responses to synthetic peptides reproducing the repeat sequences of 2 major Plasmodium falciparum antigens: the Pf155/RESA and the circumsporozoite (CS) protein. Blood samples from 83 subjects living in a rural community near Antananarivo were obtained at the beginning and the end of the transmission season. At enrollment, 40 subjects presenting with and 43 without blood parasites had similar T cell proliferative response and antibody level to all antigens tested. However, P. falciparum-infected individuals exhibited a decrease in the absolute number of T lymphocytes, due to a diminished number of CD8+ and natural killer lymphocytes. The number of CD4+ cells was similar in both groups. In the overall population, 45% of subjects had a T cell response to at least 1 RESA peptide (29-35% responding to a given peptide) and 35% to the CS protein peptide. Thirty-two percent of the donors presented with RESA antibodies and 23% had CS protein antibodies. After 20 weeks, at the end of the transmission season, cellular proliferative responses to all antigens markedly decreased as evidenced by a decrease of both the number of responders and mean stimulation indexes. Humoral response to RESA, as detected by erythrocyte membrane immunofluorescence (number of responders and mean antibody titers) markedly increased. Humoral responses to the CS protein and RESA peptides were similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221218 TI - In vitro growth inhibition of Plasmodium falciparum by sera from different regions of the Philippines. AB - Sera from different malaria endemic regions of the Republic of the Philippines were compared for their ability to inhibit growth of Plasmodium falciparum in vitro. Dialyzed serum was added to synchronous cultures containing schizonts for either the total 48 hr test period or only the last 24 hr in order to analyze the effects on erythrocytic invasion and intraerythrocytic growth, respectively. Reduction in 3H-hypoxanthine uptake was used to determine the percent of inhibition compared to nonimmune serum. One hundred seventy sera from Mindanao and Palawan in the South, the centrally located island of Mindoro, and Luzon in the North, were tested against 4 P. falciparum strains from the Philippines and 1 from Africa. Indirect fluorescent antibody titers were not predictive of inhibition. Inhibition of merozoite invasion rather than intraerythrocytic parasite growth is suggested by this study. Generally, sera were more inhibitory to parasite strains from the same geographical area than to those from more remote areas. PMID- 2221219 TI - Endemic Cryptosporidium and Giardia lamblia infections in a Thai orphanage. AB - We conducted a point prevalence survey for enteric protozoa in 205 institutionalized orphans 1-61 months of age in Bangkok, Thailand. Cryptosporidium was identified in 17 children (8%), Giardia lamblia in 42 (20%), and 3 children (1%) had both parasites. At the time of diagnosis, diarrheal symptoms were present in a minority of subjects: 36% of children with Cryptosporidium alone, 10% with G. lamblia alone, and in 20% of those with neither parasite. Although chronic nutritional status (height/age) was similar in all groups, acute nutritional status (weight/height) was lower only in children with Cryptosporidium (Z score = -1.39 +/- 0.13) compared with children with G. lamblia (mean Z score +/- SEM = -0.56 +/- 0.26) or neither parasite (Z score = 0.78 +/- 0.13; P = 0.05). Detectable levels of Cryptosporidium-specific IgG antibodies by ELISA were identified in 15 of 16 Thai children with Cryptosporidium and in 17 of 19 Thai children without Cryptosporidium (mean OD +/ SEM = 1.27 +/- 0.18 vs. 1.06 +/- 0.13, respectively), but in only 1 of 18 sera from toddlers in day-care centers in Denver, CO (OD = 0.128 +/- 0.03). Although neither infection with Cryptosporidium nor G. lamblia was consistently associated with acute diarrheal symptoms, Cryptosporidium was more often associated with depressed acute nutritional status than G. lamblia. The high prevalence of specific antibodies to Cryptosporidium in Thai orphans suggests an association between high rates of exposure with asymptomatic excretion of the parasites. PMID- 2221220 TI - Comparison of active and passive case detection of cutaneous leishmaniasis in Guatemala. AB - To estimate the degree to which passive case detection underestimates the true incidence of cutaneous leishmaniasis in Guatemala, we compared data from the passive surveillance system of the Guatemalan Ministry of Health with a cross sectional population-based survey of cutaneous leishmaniasis in Guatemala. Of the 2,938 persons interviewed, 143 (5%) reported having had cutaneous leishmaniasis at some time in the past, 37 (1.3%) reported the onset of infection in the 12 months before the survey, 31 (1.1%) had active infections, and 16 (0.5%) had parasitologically confirmed infections. Calculated on the basis of these reports and the estimated population of the endemic area, the total number of new cases in the leishmaniasis-endemic area in the 12 months before the survey was approximately 2,574; during the same 12 month period, Ministry of Health data based on passive surveillance listed 64 cases of cutaneous leishmaniasis. In Guatemala, incidence estimates based on passive surveillance may underestimate the occurrence of cutaneous leishmaniasis by as much as a factor of 40. PMID- 2221221 TI - Diffuse cutaneous leishmaniasis acquired in Peru. AB - A case of diffuse cutaneous leishmaniasis (DCL) acquired in Peru is described. The causative agent was Leishmania mexicana amazonensis as determined by isoenzyme analysis and species-specific monoclonal antibody binding characteristics. Histological examination of biopsy material showed a large number of intracellular and extracellular amastigotes and few lymphocytes. Treatment with meglumine antimoniate (Glucantime) administered iv at a dosage of 20 mg antimony/kg body weight/day for 60 days resulted in visible improvement of the lesions, but not in clinical or parasitological cure. PMID- 2221222 TI - Host immunoglobulin on spleen-derived Leishmania donovani amastigotes. AB - Leishmania donovani, an intracellular pathogen in vertebrates, is found as an amastigote within cells of reticuloendothelial origin. The spleens of experimentally infected Syrian hamsters are frequently used as a source of amastigotes for studies of host-parasite interactions, but amastigotes isolated from hamster spleens have been found to have surface-bound host immunoglobulins, which may confound interpretation of such studies. PMID- 2221223 TI - A comparison of host responses of the Mongolian jird to infections of Brugia malayi and B. pahangi. AB - Host responses of jirds receiving a single subcutaneous inoculation of subperiodic Brugia malayi were compared with those of jirds similarly infected with B. pahangi. Parasite burdens, lymphatic lesion severity, granulomatous reactivity, antibody responses to parasite antigens, and complete blood cell counts were assessed at 60 and 150 days post-inoculation. At 60 days post inoculation, percentages of adults recovered at necropsy and lymphatic lesion severity were greater in B. pahangi-infected jirds. At 150 days post-inoculation, lesion severity and percentages of worms recovered were similar in both infections. No significant differences were noted in either infection in reactivity to homologous or heterologous parasite antigens in any parameter measured. Similarities in the kinetics of the inflammatory reactivities of the 2 infections suggest that previous observations made in the jird-B. pahangi model could be utilized in designing studies using B. malayi. Further, the more marked lesion severity observed in B. pahangi-infected jirds and the relative ease of maintaining B. pahangi in the laboratory support the continued use of this system as a conceptual model for the study of lymphatic lesion pathogenesis. PMID- 2221224 TI - Transmission indices of Loa loa in the Chaillu Mountains, Congo. AB - A longitudinal entomological survey of the vectors of loiasis was conducted in the Missama area (Lekoumou region) in the Congo from September 1987 to August 1989. The principal catching site was a palm grove surrounded by forest 3 km from the village. Landing/biting densities of Chrysops were measured by standardized fly catches lasting 11 hr carried out twice a month. Vector landing densities were also assessed in the Bantu and Pygmy villages and in the fields. Populations of Chrysops from the palm grove were examined 6 times a month for infection with the infective stage of Loa loa. Chrysops silacea was the predominate vector except at the beginning of the rainy season, when C. dimidiata was the prevailing species. Chrysops were caught throughout rainy season, from October to June. The host-seeking activity of C. silacea was greatest in the middle of this season (February), but occurred sooner (October) for C. dimidiata. The following variables associated with transmission were calculated from our observations in the palm grove (the first figure corresponds to the first year of the study and the figure in parentheses corresponds to the second year). It was calculated that 2.658 (2.185) C. silacea and 1.412 (1.182) C. dimidiata could bite a person in the palm grove per year, including an average of 14.4 (12.7) infective C. silacea and 9.8 (7.2) infective C. dimidiata. The percentage of all dissected flies with third stage larvae in the head and the mean number of larvae in the head/infective fly were 0.57% and 10.1 +/- 6.8 for C. silacea and 0.66% and 11.2 +/- 6.5 for C. dimidiata, respectively. The estimated annual transmission potentials were 171.1 (102.9) for C. silacea and 116.1 (73.8) for C. dimidiata. In the palm grove, transmission was ensured by 2 effective vectors during the rainy season (October to May). Although the annual biting rate for both species was twice as low in the village as in the forest, our data suggest that effective transmission occurs there also. PMID- 2221225 TI - Variation among strains of Aedes aegypti in susceptibility to oral infection with dengue virus type 2. AB - We compared 18 Aedes aegypti strains for oral susceptibility to dengue virus type 2 (DEN-2) using a feeding protocol in which all parameters remained constant, including the titer of the infectious bloodmeal. For most strains, no significant variation between replicates was observed. Comparisons between pairs of strains showed variation of different degrees, and allowed us to characterize the strains with respect to their oral susceptibility to DEN-2. PMID- 2221227 TI - Head and neck surgery: ruminations. PMID- 2221226 TI - Isolation of Tete serogroup bunyaviruses from Ceratopogonidae collected in Colorado. AB - Two viruses were isolated from ceratopogonid midges collected in northern Colorado. Electron microscopy indicated that both isolates were bunyavirus-like. Indirect fluorescent antibody and serum dilution-plaque reduction neutralization tests showed that these isolates were members of the Tete serogroup, most closely related antigenically to Tete and Batama viruses but distinguishable from both and from each other. We suggest the name Weldona virus for these isolates. Antibody in both waterfowl and passerine birds in northern Colorado indicates the enzootic presence of these viruses in northern Colorado and raises unanswered questions about the introduction and establishment of Tete serogroup viruses in the Americas. PMID- 2221228 TI - Hayes Martin lecture. Reflections of a cancer observer. PMID- 2221229 TI - Initial failure of surgical exploration in patients with primary hyperparathyroidism. AB - To determine the causes of failures of cervical exploration for primary hyperparathyroidism, we reviewed 892 patients operated on by one surgeon from 1953 to 1990. Twenty-seven patients (3%) remained hypercalcemic or developed hypercalcemia within 6 months of surgery. Of these, five patients had one adenoma removed initially; at reoperation, three patients had a second adenoma that was successfully removed, whereas the other two patients had hyperplasia and required subtotal parathyroidectomies. No enlarged parathyroid glands were identified in 22 patients. Eventually, six patients became normocalcemic spontaneously, seven patients underwent re-exploration with a successful outcome in all but one case, two patients had ectopic hyperparathyroidism associated with carcinoma elsewhere, and seven patients refused reoperation and remain hypercalcemic. The failure rate of surgical exploration for primary hyperparathyroidism can be reduced by systematically exploring all four parathyroid glands. All abnormal parathyroids should be removed with histologic verification. When no abnormal glands are found, localization studies should be performed before re-exploration. PMID- 2221230 TI - Results of surgical treatment for hyperparathyroidism associated with renal disease. AB - Recently, the role and timing of surgery for treating secondary and tertiary hyperparathyroidism (HPT) have been questioned. In order to delineate the indications for surgery in these patients, a retrospective analysis of 53 consecutive patients treated with parathyroidectomy was conducted. Subtotal thyroidectomy was done in 37 of 45 patients undergoing their initial operations for HPT. Eight additional patients were referred after failed operations. Of 33 patients with preoperative bone pain, 70% improved. Joint pain improved in 87% of 30 patients, pruritus improved in 81% of 27 patients, and preoperative malaise improved in 73% of 33 patients after parathyroidectomy. Abdominal pain and irritated eyes were unlikely to improve. The best predictors of a successful outcome were a markedly elevated preoperative immunoreactive parathyroid hormone (mid-region) level and an elevated alkaline phosphatase level. There were no perioperative deaths. One patient (1.6%) had a recurrent laryngeal nerve injury, and one patient required reoperation for a neck hematoma. No patient had permanent hypoparathyroidism, but transient hypocalcemia (less than 7 mg/dL) occurred in 22%. Postoperative hypocalcemia correlated with elevated preoperative alkaline phosphatase levels (r2 = 0.247). PMID- 2221231 TI - Lymph node metastasis from papillary-follicular thyroid carcinoma in young patients. AB - A total of 117 patients under 20 years of age with papillary and/or follicular thyroid cancer presented to the M. D. Anderson Cancer Center between 1949 and 1987. The most common presenting symptom was a cervical mass. Twenty percent of the patients had a history of prior irradiation. Sixty percent initially had palpable lymph nodes, while 26% who had clinically negative examinations had pathologically positive lymph nodes. Recurrence was highest in regional lymph nodes at 24%, with only a 4% recurrence rate at the primary site and a 3% recurrence rate at distant sites. There were no deaths due to the thyroid cancer. To maintain a low rate of recurrence, near-total thyroidectomy with neck dissection followed by iodine 131 treatment should be considered in these young patients. PMID- 2221232 TI - Survival discriminants for differentiated thyroid cancer. AB - Since 1975, the American Cancer Society, Illinois Division, has published end results of major cancer sites drawn from patient data contributed voluntarily by hospital cancer registries throughout the state. The current study was undertaken, in part, to apprehend information regarding contested areas in the management of patients having differentiated (papillary/follicular) thyroid cancer. A total of 2,282 patients with either papillary or follicular carcinoma of the thyroid from 76 different Illinois hospitals and providing 10 years of follow-up information (life-table analysis) were retrospectively analyzed for demographic, disease, and treatment-related predictors of survival. Multivariate analysis using the Cox proportional hazards method was made for stage, age, race, sex, morphology, history of radiation exposure, presence of positive lymph nodes, initial surgical treatment, postoperative iodine 131 therapy, and replacement/suppressive thyroid hormone treatment. Statistically significant (p less than or equal to 0.05) predictors of favorable survival after thyroid cancer were low stage (I and II), young age (less than 50 years), white race, female sex, and the administration, postoperatively, of either thyroid hormone or radioactive iodine. Factors that had no influence on survival were lymph node status, choice of initial surgical treatment, and a history of prior irradiation. We suggest that where a prospective clinical trial is impracticable, a retrospective analysis of a large and detailed database, such as that available from cooperating hospital-based tumor registries, may yet provide useful insights to solutions of cancer management problems. PMID- 2221233 TI - Long-term effects of radiotherapy in childhood and adolescence. AB - The records of 50 selected pediatric patients who were treated and followed at M. D. Anderson Cancer Center were reviewed to study the late effects of nonsurgical treatment of cancer in children. There were 26 girls and 24 boys ranging in age between 2 months and 16 years. Patients with head and neck cancer received chemotherapy and radiotherapy for rhabdomyosarcoma (n = 27), retinoblastoma (n = 8), or nasopharynx cancer (n = 2). Median follow-up was 13 years. The most severe side effects were noted in the fields of radiation and included hypoplasia of the jaw, orbit, or hemi-face with varying degrees of atrophy of the overlying soft tissues. A wide range of endocrine, dental, and psychologic abnormalities was also documented. Since 1 in every 1,000 adults older than 20 years today is likely to be a survivor of childhood cancer, recommendations are made for this "new" class of patients whom the head and neck surgeon will be seeing in the future. PMID- 2221234 TI - Complications of the pectoralis major myocutaneous flap in head and neck reconstruction. AB - A retrospective review of the complications in 211 patients undergoing pectoralis major myocutaneous flap reconstruction is presented. The flap was used for mucosal lining of the oral cavity or oropharynx in 109 patients, for pharyngoesophageal reconstruction in 44, for skin coverage in 47, and for other locations in 14 patients. Flap-related complications developed in 63% of the patients. These included flap necrosis, suture line dehiscence, fistula formation, infection, and hematoma. Analysis of risk factors for the development of flap complications showed the following factors to be significant: age over 70; female gender; nomographic overweight; albumin less than 4 g/dL; use of the flap in reconstruction of the oral cavity after major glossectomy; and presence of other systemic diseases. The median length of hospitalization for those developing complications was 33 days compared with 16 days for those who did not develop any complications. Thirty-five (26%) of the 135 patients developing complications required reoperation and only 2 among these required a second flap. Similarly, only 13 of the 61 patients who developed fistulas required surgical closure. PMID- 2221235 TI - Soft tissue sarcomas of the head and neck in adults. AB - We reviewed the clinical records and pathologic material of 176 adults with primary soft tissue sarcomas treated at Memorial Sloan-Kettering Cancer Center between 1950 and 1985. Seventy-two patients (41%) had low-grade sarcomas and 104 (59%) had high-grade sarcomas. All but 18 patients underwent some form of excision as initial therapy. Adjuvant radiotherapy and chemotherapy combined with surgical excision showed no significant effect. A significantly increased risk of treatment failure was associated with large tumor size, positive surgical margins, bone involvement, local recurrence, metastatic spread, and high histologic grade. Except for recurrence, the p value by univariate analysis in the log-rank test for comparison of survival according to these clinical and pathologic characteristics was p less than 0.0001. Although the overall survival was 75% at 2 years, 55% at 5 years, and 46% at 10 years, only 20% of the patients with high-grade sarcomas were alive 10 years after treatment. Most patients with rhabdomyosarcoma, high-grade peripheral nerve tumor, and high-grade fibrous histiocytoma and all patients with high-grade angiosarcoma died of disease less than 5 years after diagnosis. New therapeutic strategies are needed to improve the survival of adult patients with high-grade soft tissue sarcomas of the head and neck. PMID- 2221236 TI - Multimodality preoperative treatment for advanced stage IV (MO) cancer of the head and neck. AB - Sixty-three patients with advanced unresectable squamous cell carcinoma of the head and neck were treated with a combination of chemotherapy, radiation, and surgery. We observed a 75% response to neoadjuvant chemotherapy. The 5-year survival rate for all 63 patients was 20%, and only 3 patients were alive at 8 years. The 5-year survival rate for patients who completed the treatment plan and received chemotherapy, radiation, and surgery was 43% compared with 20% for those who had chemotherapy and radiation but refused surgery. Development of a second primary cancer was the cause of death in 62% of the patients who survived more than 24 months. PMID- 2221237 TI - Needle aspiration biopsy in salivary gland lesions. AB - The value of needle aspiration biopsy in the evaluation and management of salivary gland pathology is controversial. The major reasons for this controversy are the difficulty in cytologic evaluation and the fact that the extent of surgery can be easily defined based on clinical judgement. However, a preoperative diagnosis is helpful in discussions with patients regarding the extent and type of surgery. Apart from the fact that needle biopsy can distinguish benign from malignant conditions, it is also very useful in distinguishing between salivary and other nonsalivary pathology. Over the past 7 1/2 years, we have performed 160 needle aspirations of parotid, submandibular, and submucosal lesions. Adequate specimens for cytologic evaluation were obtained in 155 patients (97%). A total of 84 parotid lesions, 70 submandibular lumps, and 6 submucosal abnormalities were detected. A cytologic diagnosis of benign pathology was made in 120 patients. Twelve patients had lymphoma and the diagnosis was suspected based on needle aspiration. There were 10 patients with tuberculosis and 30 patients with hyperplastic lymph nodes or benign lymphoepithelial disease of the parotid. There were three false-positive and two false-negative reports. No complications such as hematoma, nerve injury, or infection developed. The major difficulty was in distinguishing between malignancy and obstructive sialadenitis in the submandibular region. Needle aspiration was helpful in evaluating lesions in the tail of the parotid and submandibular area. The cytologic distinction between salivary and nonsalivary pathology was useful in planning the appropriate surgery and the extent of surgical resection. From a clinical standpoint, the distinction between benign and malignant salivary and nonsalivary pathology was very helpful. Preoperative diagnosis of Warthin's tumor, lymphoma, or benign lymphoepithelial disease was essential to the correct management of these patients. PMID- 2221238 TI - Early facial reanimation following radical parotid and temporal bone tumor resections. AB - A retrospective study of 35 patients who underwent early facial reanimation following extirpative parotid and temporal bone surgery requiring facial nerve sacrifice was performed. Regional facial reanimation performed immediately or within several days included 16 patients who underwent temporalis muscle transposition and 27 who underwent gold weight or eyespring lid reanimation with lower lid tightening. Simultaneous nerve grafts or nerve crossover procedures were performed in 22 patients. The authors' favored approaches to facial reanimation are discussed, with an emphasis on the value of early reanimation using properly selected techniques. PMID- 2221239 TI - Definitive mandibular replacement using reconstruction plates. AB - Mandibular defects following radical cancer surgery continue to provide challenges to head and neck surgeons. Twenty-seven patients with advanced oral cancer underwent primary mandibular replacement with metal reconstruction plates without the use of bone. Twenty-one patients (78%) had successful reconstruction with primary soft tissue healing. Six patients required removal of the plate in the postoperative period. Two of these patients had their reconstruction plates replaced as a secondary procedure following soft tissue healing. Thus, 23 of 27 patients (85%) had final mandibular reconstruction and were followed for an average of 19 months. Functional and cosmetic results were satisfactory. For patients with advanced disease, this technique compares favorably with microvascular transfer in terms of operating time and donor defect. Despite problems with plate exposure, the initial and overall success rates of 78% and 85%, respectively, make the use of these plates a reasonable choice for immediate reconstructive needs in patients with difficult tumors. PMID- 2221240 TI - Mandibular reconstruction with composite microvascular tissue transfer. AB - Microvascular free tissue transfer has provided a variety of methods of restoring vascularized bone and soft tissue to difficult defects created by tumor resection and trauma. Over 7 years, 26 patients have undergone 28 free flaps for mandibular reconstruction, 15 for primary squamous cell carcinoma of the floor of the mouth or tongue, 7 for recurrent tumor, and 6 for other reasons [lymphangioma (1), infection (1), gunshot wound (1), and osteoradionecrosis (3)]. Primary reconstruction was performed in 19 cases and secondary in 9. All repairs were composite flaps including 12 scapula, 5 radial forearm, 3 fibula, 2 serratus, and 6 deep circumflex iliac artery. Mandibular defects included the symphysis alone (7), symphysis and body (5), symphysis-body-ramus condyle (2), body or ramus (13), and bilateral body (1). Fourteen patients had received prior radiotherapy to adjuvant or curative doses. Eight received postoperative radiotherapy. All patients had initially successful vascularized reconstruction by clinical examination (28) and positive radionuclide scan (22 of 22). Bony stability was achieved in 25 of 26 patients and oral continence in 24 of 26. One complete flap loss occurred at 14 days. Complications of some degree developed in 22 patients including partial skin necrosis (3), orocutaneous fistula (3), plate exposure (1), donor site infection (3), fracture of reconstruction (1), and fracture of the radius (1). Microvascular transfer of bone and soft tissue allows a reliable reconstruction--despite previous radiotherapy, infection, foreign body, or surgery--in almost every situation in which mandible and soft tissue are absent. Bony union, a healed wound, and reasonable function and appearance are likely despite early fistula, skin loss, or metal plate or bone exposure. PMID- 2221241 TI - Reconstruction of mandibular defects in irradiated patients. AB - In this prospective study, mandibular reconstruction using titanium plates was evaluated in 31 patients treated between July 1988 and January 1990. Sixteen patients had prior surgery; 13 had prior radiotherapy. In 11 patients, prior radiation and surgery had failed. Sixteen patients received postoperative radiotherapy either in standard or accelerated fractions. Twelve patients had complications of either intraoral (8), extraoral (5), or combined (1) plate exposure or fistula formation (2). Factors significantly related to complications were poor nutrition, accelerated radiation, and recurrence. Sixty-one percent of all patients healed uneventfully. When patients with complications secondary to recurrence who subsequently died were excluded, the success rate was 73%. Only one patient had an unacceptable result that produced a cosmetic and functional deformity despite secondary repair. PMID- 2221242 TI - Long-term fate of the vascularized iliac crest bone graft for mandibular reconstruction. AB - Vascularized bone grafts, such as the iliac crest, have become a major tool for mandibular reconstruction. Due to the growing trend toward immediate bone replacement followed by implant osseointegration and dental rehabilitation, further understanding of the long-term characteristics of these grafts is essential. Early postoperative bone scans demonstrate increased activity within the vascularized graft relative to surrounding bone. This study addressed the use of bone SPECT (single photon emission computed tomography) scintigraphy as a long term method of evaluating the integrity of vascularized bone grafts. PMID- 2221243 TI - Sequential connection of flaps: a logical approach to customized mandibular reconstruction. AB - Microsurgery has improved the success rate for reconstruction of composite defects in the head and neck. Restoration of mandibular continuity alone is not adequate for reconstruction. Replacement of the oral lining with thin tissue is necessary to improve tongue mobility and to set the stage for later dental restoration. There is currently no ideal osteocutaneous free flap that provides unlimited length of bone, can undergo multiple osteotomies to produce the proper curve to the reconstructed mandible, and provides thin skin for oral lining. Combining free flaps can take advantage of the strengths of the individual donor sites and eliminate some of the problems with current osteocutaneous flaps. In six patients, a fibular osseous free flap was combined with either a radial forearm flap or a lateral arm flap to provide bone and oral lining in reconstruction of mandibular composite defects. In these selected patients, the fibula provided the blood supply for the second free flap, which was placed sequentially. The distal peroneal vessels were used to anastomose to the radial forearm vessels or the lateral arm pedicle. This approach allows the surgeon to customize the defect by improving both the functional and aesthetic aspects of reconstruction and is of use in cases where vascular access is limited, such as following head and neck surgery and radiation. PMID- 2221244 TI - Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. AB - A consecutive series of 1,081 previously untreated patients undergoing 1,119 radical neck dissections (RNDs) for squamous carcinoma of the head and neck was reviewed to study the patterns of nodal metastases. Primary tumors were located in the oral cavity in 501 patients, in the oropharynx in 207 patients, in the hypopharynx in 126 patients, and in the larynx in 247 patients. Lymph node metastases were confirmed histologically in 82% of 776 therapeutic neck dissections, and micrometastases were discovered in 33% of 343 elective RNDs. Lymph node groups in the neck were described by levels (I to V). Predominance of certain levels was seen for each primary site. Levels I, II, and III were at highest risk for metastasis from cancer of the oral cavity, and levels II, III, and IV were at highest risk for metastasis from carcinomas of the oropharynx, hypopharynx, and larynx. Supramohyoid neck dissection (clearing levels I, II, and III) for NO patients with primary squamous cell carcinomas of the oral cavity and anterolateral neck dissection (clearing levels II, III, and IV) for NO patients with primary squamous cell carcinomas of the oropharynx, hypopharynx, and larynx are recommended. PMID- 2221245 TI - Significance of positive margins in oral cavity squamous carcinoma. AB - Three hundred ninety-eight consecutive, previously untreated patients undergoing surgery for epidermoid carcinoma of the oral cavity from 1979 to 1983 were reviewed. One hundred twenty-nine patients were classified as having positive surgical margins. Of these, 83 patients had tumor within 0.5 mm of the surgical margin, 9 had premalignant changes at the margin, 9 had in situ carcinoma at the margin, and 28 had invasive cancer at the margin. The remaining 269 patients had uninvolved margins. The significance of positive margins relating to survival, subsequent clinical course, local recurrence, and patterns of treatment failure was examined, along with the impact of adjuvant postoperative radiotherapy on positive margins. The percentage of patients having positive margins progressively increased with increasing T stage: 21% in T1 versus 55% in T4 primary cancer. The overall 5-year survival for patients with negative margins was 60%. For patients with positive margins, 5-year survival was 52%. This difference was statistically significant. The incidence of local recurrence in patients having positive surgical margins was twice as much as in those with negative margins (36% versus 18%). Metastasis rates in the neck and at distant sites were not significantly influenced by the status of the surgical margin. Of the 129 patients with positive margins, 49 received postoperative radiotherapy. In those patients so treated, a trend toward lower recurrence rates was noted. Differences were not statistically significant. This retrospective review confirms the importance of adequate resection of the primary tumor as well as the relative ineffectiveness of adjuvant postoperative radiotherapy in the improvement of local control in patients with positive surgical margins. PMID- 2221246 TI - Treatment selection for carcinoma of the base of the tongue. AB - Between 1974 and 1984, 173 patients were treated for squamous cell carcinoma of the tongue base. Fifty-four patients had T1 or T2 primaries, while 115 patients had T3 or T4 tumors (4 were not staged). Lymph node metastasis was present in 120 patients. Early primary tumors treated with surgery or radiotherapy had a control rate of 83% (5 of 6 tumors) and 89% (40 of 45 tumors), respectively. For advanced primary tumors, definitive radiotherapy produced a local control rate of 55% (42 of 76 tumors), compared with 79% (23 of 29 tumors) for surgery and postoperative radiotherapy. If primary control was obtained, the regional failure rate was less than 10%. Tumor growth patterns were predictive of the response to radiotherapy. The primary control rate at 2 years for 21 patients with exophytic tumors was 84% as opposed to 58% for 62 patients with ulcerative-infiltrative tumors (p = 0.04). Radiotherapy is effective for early stage or exophytic tumors, whereas for advanced or deeply invasive tumors combined therapy enhances local control. PMID- 2221248 TI - Flow cytometric evaluation of chemosensitive and chemoresistant head and neck tumors. AB - For patients with head and neck squamous carcinoma, a clinical response to induction chemotherapy has correlated with a survival advantage. Similarly, patients with diploid tumors have displayed a survival advantage when compared with patients with aneuploid tumors. This study examined DNA content in 33 patients who had undergone induction chemotherapy as part of two clinical protocols to determine if there was a correlation between the patients with diploid tumors and the patients with a clinical response to chemotherapy. Although patients with stage III tumors had a longer disease-free survival than stage IV patients (p less than 0.0002), the addition of DNA content information did not improve the ability to predict response. Specifically, there was no correlation between DNA content and the response to chemotherapy. In addition, for this group of patients, a diploid DNA content was not correlated with a survival advantage. We conclude that DNA content information did not add significantly to the prediction of clinical outcome in these patients who received induction chemotherapy. PMID- 2221247 TI - Squamous carcinoma of the posterior pharyngeal wall. AB - We have reviewed a 12-year experience with 295 patients treated for squamous carcinoma of the pharynx in order to focus on 78 patients whose lesions arose in the posterior wall. Surgery was the definitive therapy for the primary tumor in 57 (73%), including 3 treatment groups. Thirty-two patients had limited resections that preserved the larynx, involving local excision (7 patients), anterior pharyngotomy (7 patients), lateral pharyngotomy (6 patients), median labiomandibular glossotomy (6 patients), or median mandibulotomy with paralingual extension (6 patients). The second group consisted of 21 patients with more extensive tumors who required a laryngectomy and complex reconstruction, often with postoperative radiotherapy. Finally, there were four patients who developed metachronous second primaries in the pharynx subsequent to a laryngectomy. All required flap reconstruction. Of the 21 patients whose primary treatment was radiotherapy, 5 had lesions that were implanted after access was provided by a mandibulotomy. Cumulative 5-year survival was 32% and ranged from 44% in those with favorable lesions to 15% in those with extensive tumors. Our experience highlights the variety of treatment approaches available in patients with pharyngeal carcinomas confined to the posterior wall. Surgery in this setting carries acceptable morbidity and yields survival rates that compare favorably with those achieved by external radiation therapy alone. Results in patients with extensive lesions still leave much to be desired, despite radical surgery and aggressive radiotherapy. Innovative brachytherapy techniques using surgery for access deserve further investigation. PMID- 2221249 TI - Lateral temporal bone resections. AB - Eighteen consecutive patients underwent a lateral temporal bone resection for the treatment of tumors originating in the auricle, the external auditory canal, the periauricular skin, or the parotid and were retrospectively analyzed. The different lateral temporal bone resections performed have been categorized into four types. The type I resection consists of the removal of the tympanic bone and the external auditory canal lateral to the tympanic membrane. The type II resection consists of the removal of the entire tympanic bone, the tympanic membrane, the incus, and the malleus, preserving the facial nerve and the inner ear. Type III resections remove, in addition to the those structures removed in type II resections, the distal facial nerve and fallopian canal, the mastoid tip, the styloid process, and the stylomastoid foramen. The type IV resection consists of the removal of only the mastoid tip and the inferior portion of the tympanic bone. When the techniques of lateral temporal bone resection are used appropriately, adequate surgical treatment of patients with selected advanced and recurrent malignant tumors of the external ear, the periauricular skin, and the parotid is possible with low morbidity and a high probability of local regional control. PMID- 2221250 TI - Serologic determinants of survival in patients with squamous cell carcinoma of the head and neck. AB - Specific circulating serum proteins may reflect unique properties governing the growth and progression of head and neck cancers. One hundred three previously untreated patients with squamous cell carcinoma of the head and neck were prospectively evaluated for serum IgA, IgG, and IgM and C1q-binding macromolecules. Immunoglobulins were assessed by the immunoturbidimetric technique. C1q-binding macromolecules (C1qBM) were measured utilizing the iodine 125 assay of Zubler et al (J Immunol 1976; 116: 232-5). Neither the level of serum immunoglobulins nor C1qBM values were correlated with the primary site, AJC (American Joint Committee on Cancer) stage of disease, or size of primary lesion. Likewise, comparison of serum IgA with C1qBM values demonstrated that these laboratory parameters were independent variables (r = 0.15 by Pearson linear regression). Univariate statistical analysis, utilizing the Cox proportional hazard model, showed serum IgA and C1qBM values to each contribute significantly to the ability to predict survival in patients with advanced squamous cell carcinoma of the head and neck (p = 0.01 and 0.003, respectively). Furthermore, multivariate analysis reveals that both C1qBM and serum IgA levels contribute significantly to the hazards model beyond staging in predicting survival (p less than 0.001). Predictive results were most apparent in patients with stage IV disease and related to the probability of both regional and distant metastatic recurrences. Conversely, serologic analysis provided no information in patients who were staged early. These results support pretreatment multiparametric serologic analysis of patients with squamous cell carcinoma of the head and neck. PMID- 2221251 TI - Efficacy of radical neck dissection for the control of cervical metastasis after radiotherapy for nasopharyngeal carcinoma. AB - Fifty-one patients who had persistent or recurrent neck disease from nasopharyngeal carcinoma after radiotherapy underwent radical neck dissection. The follow-up period ranged from 0.5 to 9 years (median: 2 years). Multiple cervical lymph node involvement was present in 51% of the patients (26 of 51). Malignant cells were detected in 88% of the resected specimens (45 of 51). The clinical sign of fixation of lymph node is the only factor that affects the successful control of neck disease (p = 0.04). Extracapsular extension of the nodal disease was present, and 35% of the lymph nodes were adherent to surrounding structures at operation (18 of 51). There was one hospital mortality and the overall morbidity was minimal. The actuarial survival at 5 years was 38%, and the probability of control of neck disease was 66%. Radical neck dissection is effective in controlling post-irradiation cervical metastasis from nasopharyngeal carcinoma. PMID- 2221252 TI - Cervical lymph nodes from an unknown primary tumor in 190 patients. AB - Over 10 years, 475 patients with isolated lateral neck masses were evaluated: 190 with lymph nodes from an unknown primary tumor (LNUP), 188 with neck lymphomas, 78 with benign tumors, 10 with sarcomas, and 9 with chemodectomas. This study focused on the patients with LNUP. Only 86 patients were treated with surgery (plus radiotherapy). Other patients were treated with radiotherapy (84) or chemotherapy (13) or had no treatment (7). For the overall population, failures in the neck occurred in 51% of the patients and distant metastases in 27%, while primary tumors appeared in 16%. Survival rates at 3, 5, and 10 years were 27%, 19%, and 7%, respectively, for the overall population and 45%, 35%, and 19%, respectively, for the surgical group. The diagnosis and therapeutic approach had a direct effect on neck control; failure in the neck occurred in 7 of 47 patients (15%) when fine needle aspiration and radical neck dissection with radiotherapy were performed, in 5 of 12 patients (42%) when fine needle aspiration and modified neck dissection with radiotherapy were used, in 5 of 12 patients (42%) when adenectomy diagnosis and radiotherapy treatment were performed, and in 6 of 11 patients (54%) when diagnosis by incisional biopsy was performed prior to admission, despite subsequent radical neck dissection and radiotherapy treatment. In our opinion, panendoscopy and fine needle aspiration should be the first-line diagnostic approach. When cytologic diagnosis proves impossible, the second-line approach must consist of cervical exploration with frozen section examination and excisional biopsy, followed by immediate appropriate treatment. In cases of LNUP, radical neck dissection seems to be preferable. PMID- 2221253 TI - Delayed reconstruction following Mohs' chemosurgery for skin cancers of the head and neck. AB - The case records of 52 patients with 55 cutaneous neoplasms treated by Mohs' chemosurgery and subsequently reconstructed by plastic surgeons were reviewed to determine if delay between resection and reconstruction adversely affected the outcome of reconstruction. Reconstruction was performed from 5 to 61 days after Mohs' chemosurgery for 45 basal cell carcinomas and 10 other cutaneous neoplasms. There were no complications during the interval between resection and reconstruction. Following reconstruction, minor wound complications occurred in 6% of patients; there were no major complications. Microscopic examination of the re-excised wound revealed residual disease in 2 of 45 cases of basal cell carcinoma and 0 of 10 other cutaneous malignancies. Both patients with residual basal cell carcinomas (i.e., false-negative margins after Mohs' surgery) had presented to the Mohs' surgeon with recurrent tumors. During a follow-up period of 3 months to 3 years after complete resection, recurrent tumor developed in 2 of 45 cases of basal cell carcinoma and 3 of 8 cases of squamous cell carcinoma. Delayed reconstruction, usually 5 to 20 days after Mohs' chemosurgery, can be performed without significant morbidity. Re-excision of the Mohs' chemosurgical wound for pathologic examination can detect residual disease and may be especially indicated for large recurrent wounds. PMID- 2221254 TI - Parascapular free flaps for head and neck reconstruction. AB - We report our experience with single-stage, primary reconstruction of the head and neck in 29 consecutive patients using parascapular free flaps. The commonest indications were for craniofacial defects (9), oropharyngeal soft tissue defects (10), and combined mandibular and soft tissue losses (4). Ablative surgery was performed for squamous carcinoma (22), melanoma (2), and malignant fibrous histiocytoma (2). Seven patients died of recurrent disease during a 3 1/2 year follow-up. Seven patients are alive with recurrence. Flap complications included total loss (2) due to unsalvageable microvascular thrombosis, wound breakdown with oropharyngeal fistula (2), mandibular osteomyelitis (1), trismus (2), neck contracture (1), and donor site wound dehiscence (1). The overall success of this reconstruction was 93%. Primary wound healing was the general rule with lower morbidity than with other reconstructive techniques. The flap is thin, pliable, and conforms well to three-dimensional defects. The lateral border of the scapula can be incorporated on the same vascular pedicle for single-stage mandibular reconstruction. No muscle is sacrificed, and the posterior donor defect is an added advantage. The parascapular flap is our first choice for reconstruction of major defects in the head and neck. PMID- 2221255 TI - [Pathogenesis and the principles of prevention and therapy of various types of coagulopathy in obstetrical practice (clinical lecture)]. PMID- 2221256 TI - [Maturation of the pituitary-gonadal system in girls born at term with low birth weight]. AB - Blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone have been assayed in 92 girls of 10 to 17 years of age who were term low birthweights and in 114 girls of matched ages who had normal birthweights. The girls with perinatal complications were found to have an aberrant pituitary-gonadal status: an increased FSH and estradiol level in the pubertal phase, relatively early age of menarche, delayed maturation of steroid and ovulatory ovarian function, significant incidence of menstrual disorders. These abnormalities of reproductive maturation are likely to be associated with adverse factors of the antenatal period of ontogenesis. PMID- 2221257 TI - [Tall stature and its correction in girls]. AB - The paper presents a classification of tall stature and clinical and hormonal findings in 35 girls in the age range of 11 to 18 years with constitutional tall stature. They showed a normal decline in growth hormone (GH) concentrations in the second phase of pubertal maturation. Concentrations of GH clearly correlated with the menstrual status. They were low in regularly menstruating girls, higher in non-menstruating girls and highest in tall girls with irregular menstrual cycles. Estrogen therapy in 7 girls decelerated growth rates and promoted epiphyseal ossification. Regular menstrual cycles established after withdrawal of therapy in all patients. PMID- 2221258 TI - [Comparative analysis of the data of acupuncture electrodiagnosis and hormonal status of women with oligomenorrhea]. AB - This study has compared acupuncture electrodiagnostic and hormonal data of oligomenorrheic women before and after an acupuncture regimen. According to the pretreatment hormonal status the patients were assigned to 3 groups: (1) ovarian hypofunction; (2) ovarian hypofunction with hyperandrogenism; (3) ovarian hypofunction with functional hyperprolactinemia. The treatment normalized the hormonal status in all 3 groups. The hormonal status of oligomenorrheic patients was found to correlate with conductivity of the skin at biologically active sites. PMID- 2221259 TI - [Anatomic and functional characteristics of resistant ovaries]. AB - Resistant ovary syndrome has been confirmed in 42 women using clinical, roentgenologic (craniography, hysterosalpingography, pneumogynecography, electroencephalography), genetic, sonographic, endoscopic and histologic studies. Fibrocystic breast disease was identified in 64% and normal ovarian size in 74% of the patients with resistant ovary syndrome. Progesterone test was positive in 84% of the patients. Resistant ovary syndrome was associated with higher serum estradiol levels as compared with ovarian dystrophy and pure gonadal dysgenesis. Diagnosis confirmation requires ovarian biopsy with a histological examination of ovarian specimen, but its outcome is not always significant. PMID- 2221260 TI - [Precursor diseases of the cervix uteri: pathogenesis, diagnosis and treatment]. PMID- 2221261 TI - [Follicular development during menstrual cycle and the levels of steroid hormones in the follicular fluid of women with infertility of inflammatory origin]. AB - Gonadal hormone levels have been evaluated in the follicular fluid of 67 women with tubal and peritoneal infertility. Follicular fluid concentrations of estradiol, progesterone and testosterone were compared with sonographically ascertained follicle sizes and growth rates. The results indicate a high incidence of peripheral damage of the hypothalamic-pituitary-ovarian axis in women with inflammatory diseases of the internal genitalia. PMID- 2221262 TI - [Mycoplasma infections in marital infertility]. AB - Evaluation of 302 infertile married couples has identified Mycoplasma infection in 106 (35.5%) of women and 96 (31.8%) of men. The infection was associated primarily with cervical and endometrial abnormalities in the women and sperm abnormalities in the men. Tetracycline treatment resulted in clinical improvement both in the women and men. This study suggests Mycoplasma infection to be an etiological factor in infertile marriage. PMID- 2221263 TI - [Clinico-morphological characteristics of internal endometriosis of the uterine body after menopause]. AB - A study in 100 women with postmenopausal bleedings has identified internal endometriosis of the uterine corpus in 50 of them. The diagnosis was made on the basis of past history, hysteroscopy, ultrasound scanning, roentgenotelevision hysterosalpingography, histological examination of resected uterine and adnexal tissues. Thirty patients were operated on and found to have internal endometriosis of different locations and extent as well as nodular adenomyosis. Endometriosis was functionally progressive in 29 patients and regressive in 1 patient, as was confirmed with luminescence histological examination. Ovarian hyperplasia and/or luteinization of the theca interna, stromal hyperplasia, focal thecomatosis and granulosa cell tumour which were present in 56.7% of the patients accounted for active endometriosis. Duration of postmenopause did not influence the functional activity of internal endometriosis. PMID- 2221264 TI - [Ovarian metastatic antigen in the blood serum of patients with ovarian tumors]. AB - Enzyme immunoassays of ovarian metastatic antigen 8 (OMA-8) in sera of patients with ovarian cancer have shown its elevation in 74.5% of samples. OMA-8 levels did not correlate with histology, differentiation, clinical stage of the tumour or the presence of ascites. Increased OMA-8 levels in sera of 70% of patients with stage I-II ovarian cancer suggest that it may be a marker of this disease. PMID- 2221265 TI - [Clinico-hysteroscopic characteristics of chronic endometritis]. AB - Clinical presentations of chronic endometritis have been compared with hysteroscopic findings in 60 women of reproductive age. Clinical and hysteroscopic data were indicative of a close correlation of gross endometrial abnormalities with certain symptoms of chronic endometritis and of severity and pattern of mucosal lesions of the corpus mucosa. Elucidation of clinical and hysteroscopic features of chronic endometritis permits a differential approach to the management of these patients. PMID- 2221266 TI - [Comparative evaluation of various methods of treatment of threatened abortion in patients with uterine myoma]. PMID- 2221267 TI - [The role of middle-weight molecules in the pathogenesis of late pregnancy toxemia]. AB - Serum levels of plasma-derived toxic protein components, the median weight molecules (MWM), have been assayed in 206 women with third-trimester pregnancy and in their newborns. Toxemia of various severity was present in 194 women and had developed in the presence of an extragenital disease in 84.2% (pyelonephritis, glomerulonephritis, essential hypertension, etc.). Concentrations of MWM were found to increase with deterioration of renal function and to correlate with severity of nephropathy. In every second pregnancy with toxemia, interventions included extracorporeal detoxication: ultraviolet irradiated blood autotransfusion (UIBA) and hemosorption. The rates of intra- and postpartum complications or requirement for surgery were 1.5-2-fold lower in these patients, and their newborns has better neonatal progress. Perinatal mortality of these patients was two times as low as that in the rest of the population (31.9:1000 versus 62.6:1000). The use of UIBA is recommended for mild and moderate toxemia and in combination with hemosorption for severe nephropathy. PMID- 2221268 TI - [Effect of preventive use of dexamethasone on various indicators of humoral immunity in mothers and newborn infants]. AB - In order to explore the immunosuppressive effect of glucocorticoids as accelerators of fetal lung maturity, 98 women with imminent premature labor were examined in respect to the effect of dexamethasone on IgG, IgA and IgM levels in mothers and infants. No convincing immunosuppressive effect was found on the production of the above mentioned markers of humoral immunity in the treated groups of pregnant women and their newborns. PMID- 2221269 TI - [Secretory immunity of the vagina in acute nonspecific salpingitis]. PMID- 2221270 TI - [Electroroentgenography in the diagnosis of the causes of female infertility]. PMID- 2221271 TI - [Treatment of excretory male infertility by ultraviolet irradiation of autologous blood]. PMID- 2221272 TI - [Selection of a surgical method in rectovaginal fistula]. PMID- 2221273 TI - [Morphological aspects of acute adnexitis in women of reproductive age]. PMID- 2221274 TI - [Chlamydia infections in gynecology]. PMID- 2221275 TI - Application of the Tridimensional Personality Questionnaire to a population of alcoholics and other substance abusers. AB - To assess its construct validity and application, Cloninger's Tridimensional Personality Questionnaire (TPQ) was administered to 267 inpatient substance abusers. One hundred seventy-two of the patients were alcoholic, 47 abused stimulants, and 48 abused other drugs, primarily benzodiazepines, marijuana, or were polysubstance abusers. Of the sample 33.8% were female. Analyses were conducted to (1) determine whether TPQ scores could be used to classify alcoholics as either Cloninger Type I or Type II; (2) examine the intercorrelations of TPQ scales and identify differences in these patterns due to drug of choice; (3) replicate previously obtained gender differences on the TPQ. The results indicate that (1) TPQ scores did not classify the alcoholics into the expected frequencies for Type I and Type II; (2) the scales were not independent and did not give rise to any differences among drug user groups, but (3) did confirm previously reported gender differences. These results indicate that Cloninger's model and the TPQ must be subjected to careful empirical study prior to their widespread acceptance. PMID- 2221276 TI - Learned tolerance to alcohol: mental rehearsal with imagined consequences. AB - Two experiments tested the hypothesis that the acquisition of a new response is enhanced by mental rehearsal which includes the imagined consequence of mental performance. A total of 48 males participated in the research. Experiment 1 tested drug-free learning of a motor skill task. Experiment 2 used the same task to test the acquisition of a drug-compensatory response (i.e., tolerance) under alcohol. Subjects in each experiment were randomly assigned to one of three treatments: mental rehearsal with imagined consequences (C), mental rehearsal with no imagined consequences (N), and rest (R). Both experiments confirmed the hypothesis. C treatment yielded superior drug-free performance, and a greater tolerance. The effect of N treatment was intermediate, and R treatment was least effective. It was concluded that incorporating an imagined consequence of mental performance enhances the learning of alcohol tolerance and the acquisition of a motor skill. Factors that may have contributed to the marginal efficacy of N treatment were discussed, and research implications were considered. PMID- 2221277 TI - Brain and liver dolichol in chronic alcoholism: a necropsy study. AB - Cerebral gray and white matter and liver dolichol levels were measured in postmortem samples from chronic alcoholics and nonalcoholic controls following recent suggestions that dolichol levels may be used as a marker for alcoholism. No significant differences in brain dolichol were found between the control and alcoholic groups. A significant reduction in the liver dolichol was observed in the alcoholic group. This was most marked in those alcoholics with liver disease. PMID- 2221278 TI - Genotyping of mitochondrial aldehyde dehydrogenase locus of Native American Indians. AB - Using the polymerase chain reaction to amplify genomic DNA from hair roots, we have examined the mitochondrial aldehyde dehydrogenase (ALDH2) genotypes of 28 individuals from the South American Mapuche Indians. We have determined that individuals from this population previously reported to lack (ALDH2) activity do not show the presence of the inactive (ALDH2(2] allele frequently found in Orientals. PMID- 2221279 TI - Isoenzymes of aldehyde dehydrogenase in human lymphocytes. AB - The types of isozymes of aldehyde dehydrogenase (ALDH) present in human lymphocytes has been investigated using isoelectric focusing of polyacrylamide gels followed by substrate-specific staining. Lymphocytes obtained from most individuals were found to contain both types I and II ALDH. This group of 'typical' individuals reported that they did not develop marked facial flushing or rapid heart rate after drinking alcohol nor did they develop an erythema to cutaneously applied ethanol. Lymphocytes obtained from 'atypical' individuals who do suffer from alcohol-induced flushing and rapid heart rate and who developed erythema to cutaneous ethanol displayed type II, but not type I, ALDH. Lymphocytes thus appear to be an easily accessible and suitable tissue for determining type I ALDH phenotype. PMID- 2221280 TI - Maternal genetic effects on ethanol teratogenesis and dominance of relative embryonic resistance to malformations. AB - Maternal genetic factors and/or fetal genetic factors contribute to variations in response to prenatal alcohol exposure. To assess the contribution of maternal genotype to ethanol teratogenesis, a reciprocal cross study was conducted in an animal model using C57BL/6J (B6) and long-sleep (LS) mice. B6 mice are more susceptible than LS mice to prenatal ethanol-induced malformations but both mouse stocks are susceptible to fetal weight deficits following in utero alcohol exposure. B6 and LS dams were reciprocally mated to B6 or LS males producing four embryonic genotype groups: the true-bred B6B6 and LSLS genotypes, and the genetically similar B6LS and LSB6 genotypes (the F1 genotype). Dams were intubated with either 5.8 g/kg ethanol (E) or an isocaloric amount of sucrose (S) on day 9 of pregnancy. Fetuses were removed on gestation day 18, weighed, and assessed for soft tissue or skeletal malformations. Results showed a greater litter weight deficit and increased total malformation rate in ethanol-exposed F1 litters carried by B6 mothers compared to ethanol-exposed F1 litters carried by LS mothers. This result would be expected only if maternal genetic factors contribute significantly towards susceptibility to ethanol teratogenesis. The influence of the LS mother was to decrease susceptibility to ethanol teratogenesis compared to the B6 mother while the influence of the B6 mother was to increase susceptibility to ethanol teratogenesis compared to the LS mother. The average malformation rate for F1 litters was significantly less than the predicted midparental value. This shows that the F1 genotype exhibited dominance towards resistance to prenatal alcohol effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221281 TI - Murine model of ethanol-induced immunosuppression. AB - Alcohol abuse has been associated with an increased susceptibility to infectious diseases and certain tumors. On the basis of these observations, an effect of ethanol on the immune system has been suggested. We have used a mouse model system in which male C57Bl/6 mice were fed either Lieber-DeCarli liquid diet containing ethanol sufficient to supply 37% of the total calories or isocaloric control diet in a pair-feeding design to examine the effect of ethanol on the immune system. The group consuming the ethanol-containing diet maintained relatively stable levels of blood ethanol for the 8 days of feeding. Consumption of ethanol for 8 days resulted in a profound loss of thymus and spleen cells, and the recovery of thymus cellularity was delayed relative to the recovery of spleen cell numbers after ethanol feeding was discontinued. Proliferation of spleen lymphocytes to T-cell stimuli (concanavalin A and alloantigens) was diminished; however, B-cell proliferation to lipopolysaccharide was relatively unchanged in mice fed ethanol-containing diet. Also in ethanol-fed mice a significant decrease in the primary antibody response to sheep red blood cells but not to the T independent antigen trinitrophenol-ficoll occurred. These data establish the murine model system as a means to define further the effect of ethanol on the immune system and host defense mechanisms. PMID- 2221283 TI - The detection of alcoholism in hospitalized schizophrenics: a comparison of the MAST and the MAC. AB - The Michigan Alcoholism Screening Test (MAST) and the MacAndrew Alcoholism Scale (MAC) were administered to forty-one schizophrenic inpatients also meeting DSM III criteria for either alcohol abuse or alcohol dependence and 29 schizophrenic inpatients who did not qualify for an additional substance abuse diagnosis other than marijuana abuse/dependence. The MAC failed to differentiate between the alcoholic and nonalcoholic groups and both groups scored above the recommended cutting score. The MAST significantly differentiated the alcoholic and nonalcoholic schizophrenic patients and was as sensitive to a history of alcohol abuse as to alcohol dependence. Neither the MAST nor MAC was sensitive to recent versus more remote drinking. The overall classificatory accuracy of the MAST was found to be 80% and that of the MAC was 56%. A logistic regression analysis revealed that the use of just four MAST items can yield a group classificatory rate of 83%. It was concluded that the MAST exhibited sufficient sensitivity and specificity to be used as an initial screening instrument for alcoholism in schizophrenic patients. PMID- 2221282 TI - Deranged vitamin D metabolism but normal bone mineral density in Finnish noncirrhotic male alcoholics. AB - To study the effect of prolonged ethanol consumption on calcium metabolism and on the prevalence of osteoporosis we examined 38 Finnish noncirrhotic male alcoholics (30-55 years of age) with dietary interviews and biochemical measurements and by measuring the bone mineral content of the forearm using single photon absorptiometry (SPA) and the bone mineral density of the spine, humerus and proximal femur using nonquantified computer tomography (CT) and dual energy x-ray absorptiometry (DEXA). In comparison two groups of healthy controls were studied. The mean daily dietary intake of calcium was 1.3 g in the patients and 1.2 g in the controls. The dietary intake of vitamin D was equal in the study groups, too. The serum levels of calcium, phosphate and parathyroid hormone did not show any difference between the patients and controls but in the alcoholics the urinary excretion of calcium was reduced by 42% (p less than 0.0001) as compared to the controls. The serum levels of 25-hydroxyvitamin D3, 1,25 dihydroxyvitamin D3, and 24,25-dihydroxyvitamin D3 were reduced in the alcoholics by 40% (p less than 0.0001), 23% (p less than 0.01), and 48% (p less than 0.0001), respectively, as compared to the controls. The alcoholic men had normal levels of serum testosterone and they did not have hypercortisolism. The bone mineral content of the dominant forearm measured by SPA was similar in the study groups as were the bone mineral densities (BMD) of the lumbar and humeral areas measured by CT. The BMD at the lumbar, femoral neck, Ward's triangle and trochanter sites measured by DEXA did not differ, either.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221284 TI - Esophageal motor disorder in alcoholics: result of alcoholism or withdrawal? AB - Both acute and chronic ethanol consumption may cause esophageal dysmotility. In order to systematically evaluate the effect of ethanol on esophageal motility, we studied esophageal motility in 13 healthy subjects before and following acute intravenous administration of 0.8 g/kg ethanol and in chronic alcoholics within 6 hr of their last drink (n = 6) and following 24 to 48 hr of abstinence when signs of withdrawal were present (n = 13). Withdrawing alcoholics were also restudied after intravenous administration of 0.8 g/kg ethanol. Ethanol transiently decreased lower esophageal sphincter pressure (LESP) and inhibited LES relaxation in all control subjects; this inhibitory effect of ethanol on LESP in alcoholics was significantly less, indicating the development of tolerance. Ethanol moderately decreased esophageal contraction amplitude (ECA) in 10 of 13 controls and prolonged duration of contractions in all but had no effect on velocity of esophageal contractions. In contrast, ECA was significantly elevated in both groups of alcoholics, but this was significantly more marked in withdrawing alcoholics. Ethanol infusion returned ECA toward normal values in withdrawing alcoholics. Abnormal motility was noted in three intoxicated alcoholics and 10 (77%) withdrawing alcoholics. This included nutcracker esophagus in five and hypertensive LES in two. These data indicated that (1) esophageal motor dysfunction is common in alcoholics; (2) acute ethanol administration decreases LESP and esophageal contraction amplitude, whereas chronic ethanol consumption and withdrawal from ethanol increases ECA. This suggests development of a compensatory mechanism in chronic alcoholics leading to high pressure esophageal contractions during withdrawal. PMID- 2221285 TI - Alcohol protects the diaphragm during dietary restriction. AB - We recently reported that alcoholic rat diaphragm develops greater contractile force than diaphragm of pair-fed control animals. The present experiment examines whether alcohol or dietary restriction is the more likely cause of this surprising finding. We conditioned 10 rats using a liquid diet containing ethanol as 36% of calories. Ten pair-fed control animals received an equal amount of isocaloric, ethanol-free liquid diet. Ten ad libitum control animals had unrestricted access to lab chow and water. Rats were killed after 30 weeks. Left costal diaphragm strips were studied in vitro at optimal length using direct stimulation at supramaximal voltage. Isometric force was measured and divided by muscle cross-section to compute stress. Maximal tetanic stresses developed by muscle from pair-fed controls were systematically less than alcoholic and ad libitum control values (p less than 0.0001); this did not depend on temperature (25 degrees vs. 37 degrees; p greater than 0.50). Pair-feeding increased twitch half-relaxation times (p less than 0.03) and shifted the tetanic stress stimulation frequency relationship leftward by 10 Hz (p less than 0.01). Diaphragm of pair-fed rats continued to generate lower stresses during the fatigue caused by repeated contractions (p less than 0.01). We conclude that dietary restriction associated with pair-feeding compromises diaphragm performance in rats. Chronic alcohol consumption prevents or reverses these changes, since diaphragm function of alcoholic and ad libitum control animals was not different. PMID- 2221286 TI - Late versus early onset problem drinking in older men. AB - Age at onset of problem drinking was studied in 132 older men (age 60 years and older) admitted to a VA geriatric alcoholism outpatient treatment program. Demographics, alcohol history, self reported psychological status, special treatment, and treatment compliance variables were tested for association with onset age. Late onset (defined as onset of the first alcohol problem at or after age 60) was not uncommon, occurring in 15% of the sample (29% of patients age 65 or older). Compared to earlier onset cases, late onset alcohol problems were milder and more circumscribed, and were associated with less family alcoholism and greater psychological stability. Late onset patients were also more compliant with outpatient treatment requirements; however, treatment program variables were better predictors of compliance than onset age. PMID- 2221287 TI - Inpatient treatment of employed alcoholics: a randomized clinical trial on Hazelden-type and traditional treatment. AB - The first randomized clinical trial on the Hazelden-type of treatment showed that this AA-oriented treatment for alcoholism can result in significant improvement in drinking behavior as compared to a more traditional form of treatment. One hundred forty-one employed alcoholics were randomized to either Hazelden-type treatment (N = 74) or to traditional-type treatment (N = 67). The treatment groups were highly comparable. The bimonthly follow-up lasted one year. According to the COPES-questionnaire (short form), the treatment at the Hazelden-type institute was significantly more involving, supportive, encouraging to spontaneity and oriented to personal problems than at the traditional-type institute. In accordance the treatment drop-out rate was 7.9% at Hazelden-type institute and 25.9% at traditional-type institute (p less than 0.02). The participation in outpatient treatment was significantly better after the Hazelden type treatment. The proportion of those abstinent (admitted ethanol consumption, 0 g/day; gammaglutamyl transferase, and mean cell volume were normal) was higher at Hazelden-type institute during the last (8-12 months) follow-up period (26.3% vs. 9.8%, p = 0.05). Fourteen percent of the Hazeldon-type institute patients and 1.9% of the traditional-type institute patients stayed abstinent during the whole 1-year follow-up period (p less than 0.05). The differences for the corresponding rates for controlled drinking (admitted ethanol consumption less than 40 g/day, GGT, and MCV normal) were in the same direction but did not reach statistical significance. Thus the Hazelden-type treatment obtained better results in 1-year abstinence rate than a more traditional-type treatment. PMID- 2221288 TI - Ethanol-inducible cytochrome P-450: assessment of substrates' specific chemical probes in rat liver microsomes. AB - The capacity of liver microsomes to oxidize various substrates known to be specific of alcohol-inducible cytochrome P-450 was studied in rats treated with different xenobiotics such as 3-methylcholanthrene, phenobarbital, acetone, and ethanol. Analysis of results showed a significantly marked increase following ethanol and acetone treatments of the p-nitrophenol hydroxylation (283 +/- 19% and 304 +/- 21%), N-nitrosodimethylamine (NDMA) demethylation (280 +/- 105% and 228 +/- 95%), benzene hydroxylation (258 +/- 60% and 236 +/- 61%), butanol oxidation (173 +/- 34% and 154 +/- 32%), aniline hydroxylation (147 +/- 22% and 95 +/- 8%), and ether de-ethylation (95 +/- 17% and 83 +/- 17%) and a not significant increase of N-nitrosodiethylamine (NDEA) de-ethylation (34 +/- 11% and 9 +/- 8%) in rat microsomes, respectively, versus control animals (mean +/- SD, values expressed as nmol/min/nmole P-450). All of these activities significantly decreased after 3-MC treatment, except for the p-nitrophenol hydroxylation. PB treatment markedly enhanced NDEA de-ethylation, p-nitrophenol, and benzene hydroxylations (106 +/- 38%, 109 +/- 14%, and 153 +/- 62%, respectively) versus controls. These results suggest that NDMA and especially 1 butanol are the most specific and useful probes of alcohol-inducible cytochrome P 450 in crude liver microsomes. PMID- 2221289 TI - Effects of alcohol on the import of aldehyde dehydrogenase precursor into rat liver mitochondria. AB - We previously showed that incubation of rat liver mitochondria with alcohols resulted in the inhibition of the import of aldehyde dehydrogenase precursor but not that of ornithine transcarbamylase precursor (Wang TTY, Farres J, and Weiner H: Arch Biochem Biophys 272:440-449, 1989). The time required for inhibition of import to occur was now measured with ethanol (200 mM) and butanol (100 mM) at 0 degree and 30 degrees C. It required approximately 30 min to achieve 50% inhibition with butanol and 50 min with ethanol. To further substantiate the membrane perturbing effects of alcohols, we also examined the effect of oleic acid on import. We found that incubation of mitochondria with oleic acid (0-100 microM) resulted in inhibition of aldehyde dehydrogenase precursor import in a dose response fashion. In addition to in vitro effects of alcohols on import, we conducted a preliminary study on import of protein into liver mitochondria isolated from rats fed ethanol. We found that the rate of aldehyde dehydrogenase precursor import into liver mitochondria isolated from ethanol fed rats was identical to that from control. The results are consistent with finding that the activity and amount of aldehyde dehydrogenase was the same in mitochondria isolated from the alcohol-fed or control animals. PMID- 2221290 TI - A comparison of sensitivity to oxotremorine and muscarinic receptors in LS and SS mice. AB - Several studies have suggested that ethanol interacts with muscarinic cholinergic systems in the brain. In order to assess whether muscarinic systems regulate sensitivity to ethanol, the effects of oxotremorine pretreatment on sensitivity to ethanol were determined in the long-sleep (LS) and short-sleep (SS) mice, which were selectively bred for differential sensitivity to ethanol. In addition, the relative sensitivity of these two lines to intraperitoneally (ip) injected oxotremorine and total muscarinic receptors, as measured by quinuclidinyl benzilate (QNB) binding, M1 receptor subtypes, as measured by pirenzepine (PZ) binding, and ratios of high and low agonist affinity were measured in seven brain regions. SS mice were more sensitive to oxotremorine-induced increases in sensitivity to ethanol but the LS mice were more sensitive to the effects elicited by ip oxotremorine injection. Because the effects of oxotremorine were blocked by scopolamine but not by methylscopolamine, it is likely that the effects of oxotremorine that were measured are centrally mediated. QNB binding did not differ between the LS and SS mice except for cortex where the SS mice exhibited slightly larger numbers. The mouse lines did not differ in the number of M1 receptors or in ratio of high to low affinity agonist sites. Therefore, it does not seem likely that differences in receptor numbers are important in regulating the differential sensitivities of the LS and SS mice to oxotremorine or ethanol. Differences in receptor coupling processes may be critically involved. PMID- 2221291 TI - Alterations in splanchnic blood flow following chronic ethanol exposure. AB - The purpose of these experiments was to determine whether or not tolerance develops to the effect of 3.0 g/kg ethanol on total and regional splanchnic blood flow in male Wistar rats. The animals were given the Lieber-DeCarli liquid diet containing ethanol for 10 days; ethanol-fed animals were withdrawn 24 hr prior to experiments. Regional blood flow and cardiac output (CO) were measured by the reference microsphere technique after an intraperitoneal injection of 3.0 g/kg of ethanol. Acute ethanol administration produced early nonsustained increases in portal vein blood flow in animals fed ethanol for 10 days and withdrawn for 24 hr and in control animals. However, after chronic exposure to ethanol, the pattern of increase in blood flow in response to ethanol in the splanchnic organs was different between the ethanol-fed and control groups. Increases in portal vein flow in control groups were due to concomitant increases in small intestinal, colonic, and cecal blood flow while the increase in the ethanol-fed group was due to a rise in small intestinal and stomach blood flow. The increase in stomach blood flow that occurred in the animals treated chronically with ethanol may be viewed as a conditioned response to ethanol, since this was not found in the control group. These results, demonstrate that the pattern of increase in blood flow in the splanchnic organs produced by an acute dose of ethanol depends on the animal's previous exposure to ethanol. PMID- 2221292 TI - Examination of Cloninger's type I and type II alcoholism with a sample of men alcoholics in treatment. AB - Cloninger's clinical method of classifying alcoholics into two groups (Types I and II) was examined with data obtained from 360 VA hospitalized male alcoholic patients. For operational criteria, the Cloninger clinical method of subtyping alcoholics employs age-of-onset of problem drinking and symptom-clusters supposedly associated with each subtype. Marked overlap was found between the symptom-clusters used to define the two subtypes. Ninety-one percent of the entire sample satisfied criteria for both symptom-clusters. Dividing the sample by early-onset (Type II, less than or equal to 25 years) and late-onset (Type I, greater than 26 years) alcoholism did not substantially reduce the overlap between symptom-clusters; i.e., 96% of the early-onset and 83% of the late-onset subgroups were positive for both symptom-clusters. Only 21 men (6%) could be classified when both age-of-onset and the type-appropriate symptom-cluster were used to separate patients. In hospital settings, at least, these findings suggest that the two-group clinical alcoholism typology proposed by Cloninger basically reflects the age-of-onset of problem drinking. PMID- 2221293 TI - Problems in alcoholism treatment: labeling and negative stereotyping. PMID- 2221294 TI - The type 2 primary alcoholic? PMID- 2221295 TI - Beef fat prevents alcoholic liver disease in the rat. PMID- 2221296 TI - Methanol as a marker of alcohol abuse. PMID- 2221297 TI - [Therapy of chronic pain--a task of the anesthetist?]. PMID- 2221298 TI - [Anesthesiologic complications in risk patients during and following upper and lower abdominal interventions]. AB - It was the aim of this study to determine intraoperative and postoperative complications following lower abdominal or upper abdominal surgical interventions both quantitatively and qualitatively using the risk classification of the Mannheim risk check list. The types of surgical interventions in the upper and lower abdomen can be considered as comparable in respect of influence exercised on the homeostasis. The case records of 386 patients were evaluated retrospectively who had been operated on at the biliary tract, stomach (upper abdomen) or sigma, rectum or ileocaecum (lower abdomen). Preceding diseases were noted and recorded, and so were intraoperative and postoperative complications up to the 4th postoperative week. Statistical testing was effected by means of the chi-square test with alpha = 0.05. In accordance with the determined risk classifications, the incidence of preceding diseases increased for both the types of surgery (cardiovascular diseases and pulmonary diseases being the preliminary diseases recorded in this context). If intraoperative and postoperative complications are broken down, there is a dominance of bronchopulmonary complications after upper abdominal surgery postoperatively, and an equal distribution of overall intraoperative complications. The data prove that in assessing the risk according to the Mannheim risk check list, laparotomies of the upper abdomen are underestimated, so that this type of surgery should rank higher in risk check list than large-scale laparotomies at the sigma and rectum. Over and above this, the enhanced pulmonary risk of upper abdominal surgery continuous to be a proven fact. PMID- 2221299 TI - [Unstable blood pressure during anesthesia in diabetic patients with autonomic neuropathy]. AB - Diabetic autonomic neuropathy (AN) as a risk factor of surgical procedures has so far been described in case reports, but no controlled clinical studies are known. Therefore, we intended to study systematically the perioperative relevance of the autonomic dysfunction. 32 ophthalmosurgical patients (20 diabetics, 12 non diabetics) were investigated. Cardiovascular autonomic function was examined preoperatively by a combination of tests (heart rate variations during deep breathing, Valsalva ratio, 30:15 ratio, postural hypotension, sustained hand grip). A scoring system based on these tests provided the staging of the autonomic involvement of the patients (AN score). The anaesthesiological management (thiopentone, N2O, halothane) and the operative procedure (vitrectomy) were uniform. A significant correlation was found between the AN score and the coefficient of variation of the systolic (r = 0.70, p less than 0.001) resp. the diastolic (r = 0.52, p less than 0.01) blood pressure during anaesthesia. No correlation was found between the intraoperative variability of the arterial blood pressure (coefficient of variation) and the age of the patients resp. the preoperative value of the blood pressure. In diabetics with severe autonomic neuropathy (AN score greater than 5) hypotensive reactions were seen very often during the operation. The results demonstrate that the haemodynamic stability in the perioperative period depends on the severity of the autonomic dysfunction. Diabetics with severe autonomic neuropathy have a high risk of blood pressure instability. Non-invasive diagnostic methods allow to identify these patients preoperatively. PMID- 2221301 TI - [Clonidine supplemented analgesia and sedation in prevention of postoperative delirium]. AB - In an open prospective study we investigated the efficacy of the supplementation of analgosedation by clonidine. 40 patients with oesophagus malignancy and definite alcohol abuse were on respiration therapy postoperatively after having been treated with oesophago-gastro anastomoses. With regard to manifestation intensity and development of withdrawal symptoms we found that during basic medication with piritramid-diazepam continuously i.v. administered clonidine can eliminate haemodynamic and psychovegetative symptoms related to alcohol withdrawal. The clonidine group required less analgosedation. The measurement of the urinary catecholamine output showed a normalised endogenous output. As a finding of importance the gastrovolume was reduced, and the haemodynamically firm, stable and less sedated patients of the clonidine group required fewer days of respiration therapy. Hence, the hazard of aspiration pneumonia and insufficienty anastomosis was lower. Risk of bradycardia of high potential danger did not occur with a median daily dosage of 1.09 mg/d clonidine. We consider clonidine to be a potent supplement to analgosedation for the surgical patient who is at high risk of alcohol withdrawal. PMID- 2221300 TI - [Anaphylactoid reaction to a non-ionic roentgen contrast medium in general anesthesia]. AB - The occurrence of adverse reactions is decreasing since the introduction of non ionic contrast media. Anaphylactoid reactions during general anaesthesia are rare and hitherto only documented with the administration of ionic compounds. We report an episode of hypotension, tachycardia, bronchospasm and urticaria following application of a non-ionic contrast medium (Iopamidol) during isoflurane anaesthesia. We conclude that a combinent use of anaesthesia and non ionic contrast media does not guaranty protection from anaphylactoid reactions to iodinated radiopaque compounds. PMID- 2221302 TI - [Analgesia and sedation in neurosurgical intensive care patients]. AB - Different concepts for analgosedation of neurosurgical patients are recommended during postoperative ventilation. In 30 neurosurgical patients (2 groups of 15 patients), we studied a continuous i.v. application of alfentanil (Rapifen) and midazolam (Dormicum) compared to an application of continuously given alfentanil with discontinuously given midazolam. A good analgosedation (i.e. sufficient sedation with good neurological judgement) was more frequently achieved (8/15 patients) by continuous application of both substances (alfentanil 0.023 mg/kg b.w./h, midazolam 0.10 mg/kg b.w./h), compared to discontinuous application of midazolam (4.5/15 patients; alfentanil 0.028 mg/kg b.w./h, midazolam 0.13 mg/kg b.w./h). No differences in extubation times were observed. We conclude from our results that a continuous application of both substances is superior to a discontinuous application of midazolam with continuously given alfentanil. A lower dosage of each substance is necessary to maintain a better state of analgosedation. PMID- 2221303 TI - [Case report: lumen obstruction with a Magill tube]. AB - A case is reported where a reusable red rubber tube was obstructed by a plastic capsule. This capsule was part of a washing machine for cleaning of reusable anaesthetic equipment. As a consequence we recommend the examination for free passage of each endotracheal tube before use. PMID- 2221304 TI - [Lung edema following intestinal irrigation with golytely solution]. AB - A case of pulmonary edema following whole gut lavage with Golytely's solution is reported. The patient did not suffer from gastrointestinal obstruction, renal dysfunction or cardiac congestion. PMID- 2221305 TI - [Comments on the contribution by W. Tolksdorf, H. Bremer and B. Tokic (Anasth. Intensivther. Notfallmed. 24 (1989) 94-99): "Postoperative, opiate-induced respiratory depression is not dependent on arousal"]. PMID- 2221306 TI - [Uvulo-palato-pharyngoplasty, 1-yr follow-up]. AB - Seven patients suffering from obstructive sleeping sickness syndrome and operated on U-P-P-P-., were controlled, one year later, through the polysomnographic test. The tracings showed a clear improvement compared with the preoperative records. Best results are gained in those cases with lesser apneic degree. PMID- 2221307 TI - [Sudden hearing loss and the cranio-cervical junction]. AB - Morphological alterations of the craniocervical junction as basilar impressions, a ponticulus posterior, an atlas assimilation, an intervertebral narrowing and spondylosis deformans, were found radiologically in patients with sudden hearing loss. There were no radiological differences to a healthy population. No relationship could be established between static morphological changes of the craniocervical junction of the upper cervical spine and the sudden hearing loss. However, there was a statistically significant reduction of the mobility in the upper cervical spine in patients suffering from sudden hearing loss. Very high standard deviations in the atlanto-occipital and the atlanto-odontoid joints are interpreted as hyper- as well as hypomobile joints. These results indicate a possible correlation between sudden hearing loss and a functional pathology of the craniocervical junction. PMID- 2221308 TI - [Use of local infiltration for tonsillectomy in adults under general anesthesia]. AB - The paper deals with 60 adults (aged between 13-30) tonsillectomies done under general anesthesia. The collective was alternatively divided in 2 groups, only one of them receiving local infiltration. In the infiltrated group the tonsil dissection was easier, the bleeding sparse and the follow-up less unpleasant. PMID- 2221309 TI - [Dysphonia caused by idiopathic skeletal hyperostosis. Apropos of a case]. AB - The Forestier's disease is an skeletal idiopathy described by this A. and Rotes Querol, in 1950, characterized by the systemic ossification in variable degree of the vertebral column. The neck localization can produce pharyngeal or laryngeal symptoms, due to the compression of the structures of the neighbourhood. So was the case recorded which being symptomless remain untreated. Survey of today's literature on the subject so as diagnosis, pathophysiology and its management. PMID- 2221310 TI - [Otitis externa maligna. Our experience]. AB - The AA. expose the experience gained through a group of 9 cases of malignant external otitis. They review the previous circumstances, assess the results of medical and/or surgical treatment and the evolution of the processes, emphasizing the importance of prognostic factors. Twenty-two per cent was the rate mortality. PMID- 2221311 TI - [The presentation of cleft palate in isolation or as part of a syndrome]. AB - Clefting of the palate may be complete or incomplete (bifid uvula, submucous cleft palate). Cleft palate with or without cleft lip is part of many different syndromes, which are briefly reviewed with highly selected references. PMID- 2221312 TI - [Characteristics of cardiopulmonary resuscitation in pregnant women]. AB - Cardiopulmonary resuscitation (CPR) during pregnancy is a rare event, but due to the increasing number of pregnant women with significant medical disorders it will gain more importance in the near future. Effective CPR with respect to survival of mother and infant can only be accomplished under optimal conditions. We discuss important pathophysiological alterations during pregnancy and, including recommendations in the available literature, we present a standardized protocol for life support for mother and infant. The protocol depends on the progress of the pregnancy. Compared to non-pregnant patients, pregnant women must be placed in a left lateral position immediately. If possible, the decision to perform open-chest CPR has to be made within 15 min of unsuccessful closed-chest CPR. In addition, during late pregnancy there should be no delay in performing an emergency cesarean section, even during CPR. PMID- 2221313 TI - [Anesthesia induction in children: propofol in comparison with thiopental following premedication with midazolam]. AB - Propofol provides smooth and rapid induction of anesthesia in adults and guarantees rapid recovery. The use of propofol in adults is frequently associated with pain on injection, but this can be reduced by: (1) injection into the relatively large veins in the forearm or the antecubital fossa: (2) addition of lignocaine to the propofol; or (3) injection of an opioid (alfentanil) before propofol. Compared with experience in adults, there is very little experience with propofol in pediatric anesthesia. The aim of this random prospective study was to compare the induction characteristics of propofol and thiopentone in pediatric anesthesia. Vigilance and behavior in the postoperative period were also compared. METHOD. A total of 75 healthy children aged 3-12 years who were undergoing elective operations were studied. All the children received premedication with 0.5 mg/kg midazolam with 0.02 mg/kg atropine by the rectal route. The children were divided randomly into 3 groups and received: group A, thiopentone 3-6 mg/kg; group B, propofol 1-3 mg/kg mixed with lignocaine (10/200 mg); group C, propofol 1-3 mg/kg, followed 1 min later by alfentanil 0.01 mg/kg. The induction agent was injected over 30 s, if possible into the vein in the forearm or the antecubital fossa. The immediate reaction on vein puncture and any discomfort during the injection were noted. After intubation the anesthesia was maintained with 1 vol% halothane, nitrous oxide and oxygen (2:1). Arterial pressure was measured on arrival in the induction room, immediately after the induction of anesthesia, immediately after intubation and thereafter at 5-min intervals throughout the anesthesia. Heart rate (ECG) and arterial oxygen saturation (saO2) were measured continuously. The existence of any anterograde amnesia was tested (age over 4 years) by means of one of 6 pictures shown to each before operation. The ability to recall the picture shown was recorded 2-5 h postoperatively. The completeness of recovery was assessed at 10-min intervals up to 1 h, and thereafter at 1-h intervals. In the postoperative period a recovery test (postbox test) was performed. The incidence of side effects during the induction of anesthesia and also during recovery and the postoperative period (for 5 h) was recorded. RESULTS. There was no significant difference between the children in the 3 different groups with regard to age, body weight, type of operation, or duration of anesthesia. Among the total of 75 children, 66.7% accepted the vein puncture very well, and 24% well. In some children in each group we observed obstruction of the respiratory tract (group A, 36%; group B, 48%; group C, 64%). Apnea for 20 s was observed only in groups B and C (2 and 3 children respectively). During spontaneous respiration with room air there was a significant decrease of the arterial oxygen saturation about 1 min after induction in all groups. In children ventilated with oxygen by mask, the SaO2 remained nearly constant... PMID- 2221314 TI - [Hemodynamics and myocardial energy balance in coronary surgery patients during high-dose fentanyl-pancuronium anesthesia and modified neurolept-pancuronium anesthesia]. AB - In 8 patients with coronary artery disease (CAD) classed as NYHA II or III, anesthesia was induced with high-dose fentanyl (0.05 mg/kg) and pancuronium (0.1 mg/kg). The patients were ventilated normally with the aid of a mask (O2: air 1:1, tidal volume 10 ml/kg with a rate of 10/min) for 5 min and then intubated. In 8 further patients with CAD NYHA class II or III, anesthesia was induced with 0.02 mg/kg flunitrazepam, N2O/O2 1:1 and isoflurane 0.5 vol%; they were relaxed with pancuronium (0.1 mg/kg) in combination with a bolus of 0.005 mg/kg fentanyl. These patients were also ventilated normally for 5 min and then intubated. Measurements of cardiovascular dynamics included cardiac output (CO), heart rate (HR), arterial pressure (AP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), myocardial blood flow (MBF), and arterial and coronary sinus oxygen and lactate contents. Cardiac index (CI), stroke volume index (SVI), total peripheral resistance (TPR), myocardial oxygen consumption (MVO2), coronary vascular resistance (CVR), coronary perfusion pressure (CPP), myocardial oxygen content difference (AVDO2cor) and myocardial lactate extraction rate (LE) were calculated from standard formulas. Measurements and an electrocardiogram were taken before anesthesia, after induction of anesthesia and after intubation. The hemodynamic parameters HR, AP, CI, CPP were relatively stable in patients anesthetized with high-dose fentanyl and pancuronium, whereas we found greater decreases in these parameters with the balanced anesthesia technique. Determinants of myocardial oxygen demand were higher in the high-dose fentanyl group; therefore, myocardial blood flow and oxygen consumption did not decrease to the same extent as in the balanced anesthesia group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221315 TI - [Problems of intubation using the flexible LF-1 fiberoptic bronchoscope. Development of an intubation aid]. AB - Fiberoptic endotracheal intubation with an endoscope (external diameter 4 mm) especially designed for anesthesiologists proved to be safe providing small diameter tubes were used. The use of large-diameter tubes (I.D. 7.5-8.5 (mm)) involves a risk of the tip of the tube clinging to the arytenoid cartilages preventing any further advancement. To avoid this complication another special tube has been constructed, which fills the space between the endotracheal tube and the bronchoscope and centers the bronchoscope within the endotracheal tube. When this new tube was used there were no problems either in passing the bronchoscope through this "inner" tube or in withdrawing the inner tube after successful intubation. With the new device it was even possible to pass tubes with wider lumen into the trachea over the fiberscope with minimal difficulty and trauma. PMID- 2221316 TI - [Intraoral dental fixation of an endotracheal tube using a cofferdam clamp]. AB - Extraoral tape fixation of the orotracheal tube for general anesthesia is a major problem in maxillofacial surgery. First of all, surgical access to the perioral and nasal region is handicapped by the tape covering and distracting the skin, especially in those cases where no nasotracheal intubation is possible; furthermore, blood, saliva, and disinfectant fluid interfere with reliable adhesion of the tape. A method of intraoral dental fixation of the orotracheal tube by a rubber dam fixation clamp is presented. The rubber dam isolates teeth against the oral cavity, providing a dry operative field to the dentist. The set of clamps, each designed according to the individual anatomy of the different teeth, is usual in the dental trade. After intubation the selected clamp is placed on the tooth by means of the forceps. The tube is laid on the clamp and tied on by a silk thread (2 x 0), which is inserted through the clamp's holes. We recommend fixation to the teeth in the mandible to avoid tension load, which could strain teeth in the maxilla; as far as possible only teeth without any impairment (e.g. loosening) should be selected. CONCLUSION: The method of intraoral dental fixation of the orotracheal tube by a rubber dam clamp offers the following advantages: (1) the surgeon, especially the maxillofacial surgeon, has a good view of the perioral region and free access for surgery; there is (2) no skin distraction or irritation by tape; there is (3) reliable tube fixation even for patients with allergy to adhesive materials; there is (4) no solution of tape fixation by blood, saliva, or disinfectant fluid; and (5) silk sutures cannot be subjected to strain when solving tape fixation. PMID- 2221317 TI - [Comments on the paper by J. Schou et al. The double mask]. PMID- 2221319 TI - Symposium issue: obstetric anesthesia. Proceedings. PMID- 2221318 TI - The Minnitt Gas/Air Apparatus (Queen Charlotte model). PMID- 2221320 TI - Epidural opioids in obstetrics--a review. AB - Epidural opioids have been used in obstetrics since 1980. Various opioids are reviewed in relation to their pharmacology, their efficacy in labour, during caesarean section and for postoperative analgesia, their side-effects and safety. In this patient population it appears safe to administer epidural opioids on the general ward provided that strict monitoring standards are maintained. Practical considerations of nursing management are discussed. PMID- 2221321 TI - Epidural medication after the initial dose: reflections on current methods of administration during labour. AB - Most women who receive epidural pain relief during labour require additional epidural analgesia following the initial dose. This review examines the relative merits associated with current methods of epidural drug delivery when further analgesia is required. Apart from considerations of patient safety and convenience the review compares the relative flexibility in pain management which can be provided by these different regimens. It is postulated that patient satisfaction is enhanced when the mother has some personal control over the density of neural blockade provided by epidural analgesia. PMID- 2221322 TI - Monitoring epidural analgesia in the parturient. AB - Appropriate monitoring during obstetric epidural analgesia consists of: 1. Indirect BP and pulse monitoring before epidural insertion, frequently after every dose, and intermittently thereafter. 2. The aspiration test before all injections. 3. Frequent clinical monitoring for signs of intravascular injection during administration of small intermittent doses (not more than 3-5 ml at a time). 4. Frequent clinical monitoring for sympathetic, sensory and motor signs indicating upward extension of the block. 5. Frequent monitoring of the fetal heart rate (FHR) and other signs of fetal welfare. In many instances continuous tocogram with fetal heart rate (CTG) monitoring is useful. We do not believe CTG use is mandatory for epidural analgesia in the uncomplicated pregnancy, but we do advocate that it (and other appropriate fetal monitoring techniques) be used when risk factors or complications, either fetal or maternal, are present or suspected. The anaesthetist should be familiar with fetal monitoring techniques, their use and interpretation. He or she should be prepared to recommend their use when it is considered appropriate to do so. PMID- 2221323 TI - The place of caudal anaesthesia in obstetrics. AB - Present day trainee anaesthetists could be forgiven if they finished their anaesthetic training believing that caudal anaesthesia in obstetrics is not only unnecessary, but dangerous and a relic of the past. Many anaesthetic texts teach applications and techniques which are little or no advance on the teachings of Hingson and Edwards in 1942 and reflect nothing of the true value and application of this valuable block. This paper presents a critical review of these texts and of the results of the use of the block in a busy obstetric unit. PMID- 2221324 TI - Epidurals, spinals and bleeding disorders in pregnancy: a review. AB - Paraplegia caused by spinal haemorrhage is a very rare but disastrous complication of spinal or epidural insertion. The risk in uncomplicated surgical and obstetric patients is outlined. Bleeding disorders in pregnant patients may prevent the use of major regional anaesthesia. Factors which influence the choice of anaesthetic technique for patients with pregnancy-induced hypertension, von Willebrand's disease, and anticoagulation therapy, are discussed. PMID- 2221325 TI - Anaesthesia and the sick foetus. AB - The primary cause of foetal illness is placental pathology. The use of diagnostic ultrasound allows for a better understanding of how the foetus may be compromised by inadequate placental function. Anaesthesia affects placental function by changing uteroplacental and umbilical placental perfusion. Regional anaesthesia may have a beneficial effect on these circulations although general anaesthesia may be adapted to produce minimal disturbance of placental circulatory dynamics. The advantages and disadvantages of particular anaesthetic techniques in the delivery of the sick foetus are discussed. PMID- 2221326 TI - Management of failed endotracheal intubation at caesarean section. AB - A review of the history of endotracheal intubation and endotracheal tubes is presented and a plan of management of failed endotracheal intubation at caesarean section is described. The importance of preparation for such an event by incorporation of certain features into anaesthesia training programs is emphasised. PMID- 2221327 TI - Haematological disorders responsible for maternal bleeding in late pregnancy. PMID- 2221328 TI - The Melbourne Chart--a logical guide to neonatal resuscitation. AB - Resuscitation of the asphyxiated infant is one of the great emergencies in medical practice. Properly done, it can save many lives and greatly reduce the morbidity resulting from hypoxic-ischaemic encephalopathy, but if it is ineptly performed, the effects of hypoxic-ischaemic encephalopathy may be accentuated, with resultant increased morbidity and even mortality. Other than paediatricians, few practitioners have regular experience in neonatal resuscitation: indeed many, including obstetricians, anaesthetists, general practitioners and midwives may only rarely face the problem of severe asphyxia. It is therefore essential for the occasional practitioner to have ready reference to a logical guide to resuscitation. We have designed such a guide which is widely distributed in delivery suites and operating theatres in Victoria. Its basic form has been in use for over a decade and it has recently been revised. Use of the chart assists the resuscitator to judge the level of resuscitation required. It is our experience that much unnecessary intervention occurs at resuscitation, and we believe the methods outlined in this schematic chart represent a more conservative but logical approach to neonatal resuscitation. The chart is based on the pathophysiological changes that occur in perinatal asphyxia, directing the user to the appropriate manoeuvres required to correct those changes, depending on the degree of asphyxia which is determined by clinical signs and by use of the Apgar score. PMID- 2221329 TI - Drug dependence and pregnancy: antenatal and intrapartum problems. AB - The last decade has seen an increase in the use of illicit drugs and alcohol in the community including an increase in the use of these agents by women in the reproductive age group. With this in mind, health-care workers need to avoid being complacent in caring for these women--they are a high-risk obstetric population with a significant incidence of medical, obstetric and paediatric complications. This paper concentrates on the antenatal and intrapartum problems, and outlines their management. An overview of the problem is presented as well as an illustrative case report. PMID- 2221330 TI - Management of severe pregnancy-induced hypertension, or gestosis, with sodium nitroprusside. PMID- 2221331 TI - Pulmonary hypertension and pregnancy--a lethal combination. AB - Pulmonary hypertension may be either primary of unknown aetiology or secondary to existing cardio-respiratory disease. As a single entity the prognosis is poor but superimposition of the physiological changes of pregnancy and labour produces a lethal condition. This paper sets out two clinical cases of primary pulmonary hypertension as background for discussion to highlight the issues involved. Whatever this discussion does, let it be clearly spelled out that prevention is better than any proposed cure. PMID- 2221333 TI - Predictors of mortality in children with respiratory failure: possible indications for ECMO. AB - There are many unproven methods of ventilation and oxygenation that have been used in children dying from respiratory failure, including extracorporeal devices and high frequency ventilation. However, no objective predictors of death have been developed that enable clinicians to decide when it is reasonable to use these therapies in children over one month of age with acute respiratory failure. To determine predictors of death, we evaluated the charts of all 42 children aged one month to eighteen years admitted to the intensive care unit who were ventilated for more than twelve hours, received greater than 90% oxygen, received a peak inspiratory pressure greater than 25 cmH2O and had no pre-existing neurodevelopmental handicap. A combination of a variable reflecting ventilation and a variable reflecting oxygenation reliably predicted death: a combination of ventilation index greater than 40 and oxygenation index greater than 0.4 was associated with a 77% chance of mortality (sensitivity 65% and specificity 74%); a combination of peak inspiratory pressure greater than 40 cmH2O and A-aDO2 greater than 580 was associated with an 81% chance of mortality (sensitivity 74% and specificity 79%). These criteria may be useful in predicting death from respiratory failure in children. PMID- 2221332 TI - Role of repeated doses of oral activated charcoal in the treatment of acute intoxications. AB - While single dose activated charcoal is effective in preventing drug absorption, repeated doses not only prevent absorption but also can increase systemic drug clearance. The mechanism for the latter effect may involve interruption of enterohepatic recycling and/or promotion of drug exsorption from the systemic circulation into the gut lumen. A comprehensive review of reported studies in volunteer subjects and overdose patients showed that repeated dose activated charcoal markedly decreased the half-life and/or increased the clearance of a wide range of drugs. Side-effects of the treatment were infrequent, but included aspiration pneumonia, diarrhoea and constipation. The addition of laxatives to repeated dose charcoal treatment did not offer any significant increase in drug clearance and is not recommended. It is suggested that the optimal regimen for the use of repeat dose activated charcoal in acute drug intoxications is an initial dose of 75-100 g, followed by 50 g every 4 hours until the risks of systemic drug toxicity are reduced to an acceptable level. PMID- 2221335 TI - Inadvertent spinal anaesthesia with 0.125% bupivacaine and fentanyl during labour. PMID- 2221334 TI - Halothane reductive metabolism in an adult surgical population. AB - The reductive metabolism of halothane was studied in 34 adult patients undergoing routine surgery. Reductive biotransformation of halothane was more extensive in females than males and was also enhanced in two patients treated preoperatively with phenytoin, an enzyme-inducing drug. Tobacco, ethanol and the patient's age, body weight and previous exposure to halothane did not influence reductive metabolism of halothane. PMID- 2221336 TI - Hyperbaric oxygen for cerebral arterial air embolism occurring during caesarean section. PMID- 2221337 TI - Three cases of anaphylactoid reaction to Haemaccel. PMID- 2221338 TI - Obituary: a man of history-- Douglas Joseph. PMID- 2221339 TI - Malignant hyperpyrexia and oxygen consumption. PMID- 2221340 TI - Respiratory arrest with epidural fentanyl. PMID- 2221341 TI - Avoiding needle-stick injury. PMID- 2221343 TI - Failure of endotracheal tube cuff deflation. PMID- 2221342 TI - Peritoneal dialysis in ICU. PMID- 2221344 TI - Trilene afficionados. PMID- 2221345 TI - Percutaneous dilational tracheostomy--a caution. PMID- 2221346 TI - The use of a multichannel scaling method to detect radioactive species in spread monolayers. AB - This study describes a simple and inexpensive method for monitoring radioactive species spread as monolayers at the air/water interface. The combination of a discriminator and multichannel scalar counter with a personal computer functions to unify all measurements, to simplify the operational process and data acquisition, and to provide a real-time display of the data. Its use is demonstrated by following the hydrolysis of L-alpha-[1-14C]dioleoyl phosphatidylcholine by the enzyme, phospholipase A2, isolated from the porcine pancreas. PMID- 2221347 TI - Electrophoretic detection of ascorbate oxidase activity by photoreduction of nitroblue tetrazolium. AB - A method for the detection of ascorbate oxidase in electrophoretic gels is described. This method relies on the ability of the enzyme to prevent the photoreduction of nitroblue tetrazolium (NBT). The method is based on that described by C. Beauchamp and I. Fridovich (1971, Anal. Biochem. 44, 276-287) for the superoxide dismutase and was made specific for ascorbate oxidase detection by treating the gel with 0.1 M hydrogen peroxide. Ascorbate (25 microM) or riboflavin (500 microM) was used as the electron donor. The possible reaction mechanism in the presence of ascorbate has been investigated. Western and Northern blot analyses confirmed the results obtained from the NBT staining procedure. PMID- 2221348 TI - A radioisotopic assay for polyamine oxidase. AB - A new radioisotopic assay for polyamine oxidase with N1-acetylspermine as substrate is presented. A modified method for the chemical synthesis of radioactive N1-acetylspermine, which gave a good yield, is also described. The reaction mixture, containing N1-[14C]acetylspermine and tissue homogenate, was incubated for the enzyme reaction and applied to a minicolumn of Amberlite CG-50. The reaction product 3-[14C]-acetamidopropanal did not adsorb to the column, but passed through it; thus the eluate could be directly subjected to liquid scintillation counting. The blank levels were low and relatively constant even with crude tissue homogenates. The detection limit obtained was 0.05 nmol per tube. This method is simple, highly sensitive, and highly specific. PMID- 2221349 TI - 2,4-Dinitrophenyl [14C]cysteinyl disulfide allows selective radioactive labeling of protein thiols under spectrophotometric control. AB - 2,4-Dinitrophenyl [1-14C]cysteinyl disulfide readily introduces by disulfide exchange [14C]cysteine as a label into proteins with exposed thiols. The release of an equivalent amount of colored 2,4-dinitrothiophenolate allows the labeling reaction to be followed spectrophotometrically. In reaction with two cysteine residues of rabbit skeletal muscle actin, the thiol selectivity of the reagent corresponded to that of 5,5'-dithiobis(2-nitrobenzoic acid) (Ellman's reagent) and was superior to that of N-[14C]ethylmaleimide. Labeling of single SH groups of actin and papain proceeded faster than titration with Ellman's reagent under the same conditions. The [14C]cysteine label could be removed under mild conditions, e.g., with dithiothreitol, but proved to be stable during cyanogen bromide degradation of the protein and peptide purification. 2,4-Dinitrophenyl cysteinyl disulfide can be easily prepared within a few hours. PMID- 2221350 TI - Application of sodium dodecyl sulfate-gel electrophoresis to low molecular weight polypeptides. AB - Experiments with nine polypeptides with molecular weights between 2000 and 10,760 confirm the value of sodium dodecy sulfate (SDS)-gel electrophoresis for separating polypeptides in this molecular weight range. In one case, electrophoretic blotting and microsequencing were successfully carried out. However, molecular weight determination in the low molecular weight range (less than 10,000) is much less reliable than that in the conventional molecular weight range (greater than 10,000) for SDS gels. Information provided by suppliers of horse heart myoglobin fragment kits is potentially misleading. PMID- 2221351 TI - High-performance liquid chromatographic analysis of radiolabeled inositol phosphates. AB - Separation of inositol phosphates by low-pressure anion-exchange chromatography yields unsatisfactory results, while previously described anion-exchange HPLC methods require such extensive processing times that they preclude efficient sample analysis. Using a low-capacity Vydac nucleotide anion-exchange column, we have developed a method which allows complete separation of myo-inositol, inositol 1-phosphate, inositol 1,4-bisphosphate, inositol 1,4,5-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate in approximately 10 min followed by a 5 min column regeneration time. This method provided exceptional reproducibility and quantitative recovery of each inositol phosphate. One column was used for over 300 separations with no loss in performance or alteration in elution pattern. A modified procedure with a 14-min gradient was developed to separate the 1,3,4- and 1,4,5-isomers of inositol trisphosphate. These separation procedures were used to characterize the kinetics of degradation of inositol phosphates by lysates of erythrocytes and neutrophils. We conclude that these procedures are applicable for rapid and quantitative analysis of radiolabeled inositol phosphates in cellular extracts. PMID- 2221352 TI - Difference between histidine and histamine in the mechanistic pathway of the fluorescence reaction with ortho-phthalaldehyde. AB - Histamine reacts with ortho-phthalaldehyde (OPA) in an alkaline medium to form an unstable fluorescent adduct (Fbase-Hm). Acidification of the solution to pH 2-4 gives a stable and highly fluorescent adduct (Facid-Hm). In contrast, histidine develops a relatively stable fluorescent adduct (Fbase-Hd) with OPA in an alkaline medium. Upon acidification of the solution, however, only trace amounts of the alternative fluorescent adduct (Facid-Hd) are produced although Fbase-Hd disappears similarly to Fbase-Hm. In this paper, the reaction pathway of histidine with OPA was clarified by the kinetic analysis of formation and degradation of Fbase-Hd. In comparing the results of this study with the previous ones for histamine (T. Yoshimura et al., 1987, Anal. Biochem., 164, 132-137), we elucidate the difference between histamine and histidine in the mechanism of fluorescence reaction with OPA. The presence of the carboxyl group in histidine not only stabilizes Fbase-Hd in an alkaline medium but also prevents the formation of a 1:2 adduct of histidine and OPA, the precursor of Facid-Hd. PMID- 2221353 TI - Preparative high-performance liquid chromatography purification of polyunsaturated phospholipids and characterization using ultraviolet derivative spectroscopy. AB - A preparative reversed-phase HPLC system utilizing an isocratic mobile phase to purify up to 10-mg quantities of phospholipids is described. The method was developed to separate oxidation products of polyunsaturated phospholipids from intact, parent lipids. The method is useful for phosphatidylcholine and phosphatidylethanolamine on a preparative scale and for phosphatidylserine and phosphatidic acid on an analytical scale. Both intact phospholipids and oxidized phospholipids were monitored by absorbance at 206 nm. The oxidation products were simultaneously monitored at 234 nm where the intact phospholipids have only a very slight end absorption. Second-derivative uv spectroscopy proved to be extremely useful to identify the presence or to verify the absence of oxidation products in phospholipid samples. For autoxidized docosahexaenoic acid containing phospholipids, the absorbance maximum of diene oxidation products is 237 nm for the trans,trans (t,t) isomer and 246 nm for the cis,trans (c,t) isomers. Similarly, five classes of triene oxidation product stereoisomers have distinct absorbance maxima detected by second-derivative spectroscopy ranging from 269 to 292 nm. PMID- 2221354 TI - Colorimetric determination of N-acetylhexosamine-terminating O-glycosidically linked saccharides in mucins and glycoproteins. AB - A sensitive colorimetric assay for detecting mucins and glycoproteins rich in O glycosidically linked saccharides is reported. The method combines the susceptibility of N-acetylgalactosamine terminating O-glycosidically linked saccharides to beta-elimination with the Morgan-Elson reaction for N acetylhexosamines with free reducing ends. All mucin and mucin-type glycoproteins but none of the serum-type glycoproteins tested resulted in characteristic color production. All mucins tested gave linear responses in the range 5 to 200 micrograms and the assay was also adapted to the microscale involving the use of 96-well microtiter plates. The microassay in which the volumes of samples and reagents are scaled down 2.5-fold was particularly useful in monitoring of mucins, in the presence of other glycoconjugates, in large numbers of samples obtained during fractionation procedures. Cesium chloride, cesium bromide, potassium thiocyanate, and various detergents do not interfere with the colorimetric determination. Guanidine hydrochloride, cesium trifluoroacetate, and beta-mercaptoethanol decreased color by 30 to 45%; however, the interference was not serious to prevent the use of the method for detection of mucins in their presence. The use of the method for the specific detection of mucin during fractionation by gel filtration and density gradient centrifugation of cystic fibrosis sputum samples is demonstrated. PMID- 2221355 TI - Preparation and characterization of monoclonal antibodies to an N-linked oligosaccharide. AB - Two monoclonal antibodies to an N-linked oligosaccharide, MT-5 and MT-9, have been prepared by immunization with a pyridylaminated, asialylated, galactosylated, fucosylated, bisected biantennary sugar. The reactivity of these antibodies was monitored by their reaction with human asialoglycophorin in a solid-phase enzyme-linked immunosorbent assay. Both antibodies reacted with the sugar chains of various human glycoproteins such as immunoglobulin G, transferrin, gamma-glutamyl transpeptidase, alpha 1-acid glycoprotein, and alpha fetoprotein. Treatment of asialoglycophorin with beta-N-acetylhexosaminidase or alpha-mannosidase resulted in reduction of the binding to these antibodies. The reactivity of MT-5 to asialoglycophorin was slightly inhibited by D-mannose and N acetylglucosamine, whereas that of MT-9 was inhibited by D-mannose, N-acetyl-D glucosamine, chitobiose, and L-fucose. The epitope specificity of MT-5 appears to be a sugar chain containing biantennary N-acetyl-D-glucosamine residues, the bisected N-acetyl-D-glucosamine residue, and a trimannosyl core. The epitope to which MT-9 is directed may be a complex made up of beta-mannose, chitobiose, and L-fucose. These studies indicate that immunization with pyridylaminated sugars can produce antibodies that recognize N-linked oligosaccharides. Monoclonal/polyclonal antibodies to the N-linked sugar chains of glycopeptides would be useful in such studies of proteins. PMID- 2221356 TI - Conditions influencing yield and analysis of 8-hydroxy-2'-deoxyguanosine in oxidatively damaged DNA. AB - We have conducted studies to obtain practical knowledge regarding the stability, digestion, and analytical determination of the content of 8-hydroxy-2-deoxy guanosine (8-OHdG) in oxidatively damaged DNA. Utilizing H2O2 plus uv light to form oxidatively damaged DNA, we found that storage of the DNA at -20 degrees C at alkaline pH caused a significant loss of 8-OHdG, whereas storage at -20 degrees C at neutral or acidic pH prevented loss of 8-OHdG. The 8-OHdG within DNA is stable at 100 degrees C for at least 15 min. Formation of 8-OHdG within DNA using uv light and H2O2 as a hydroxyl free radical-generating system yields the highest amounts when low levels of phosphate buffer are used; but the use of Tris or citrate buffers causes a lower yield of 8-OHdG because these buffers act as scavengers for the hydroxyl free radicals. Independent assessment of hydroxyl free radical flux by the use of salicylate trapping allows assessment of competitive radical reactions. Ethanol washing of plastic microfuge tubes prior to DNA enzymatic digestion improved the yield of 8-OHdG and reduced the variability between samples. Digestion of the oxidatively damaged DNA by the use of a method involving DNase I, endonuclease, phosphodiesterase, and alkaline phosphatase produced the highest yield of 8-OHdG. PMID- 2221357 TI - Identification of FAD, FMN, and riboflavin in the retina by microextraction and high-performance liquid chromatography. AB - The presence of flavins in the retina has been known for some time. However, the small size of the tissue has made it difficult to quantify the levels of the individual flavins, riboflavin (RB), FMN, and FAD without pooling large numbers of retinas. A procedure to extract and quantitate RB, FMN, and FAD in retinal tissue from as few as four rat retinas has been developed. The procedure resolves these three classes of flavins and provides a recovery near 100%. For the analysis, HPLC using a reverse-phase column with cyclohexyl functional groups was coupled to a fluorescence detector. The microextraction-HPLC procedure was reproducible for the quantitative analysis of flavins in the retina and equally applicable for analysis of flavins in liver and plasma. PMID- 2221358 TI - Analysis of beta-hydroxy-beta-methyl butyrate in plasma by gas chromatography and mass spectrometry. AB - A method for measuring the branched chain hydroxy acid beta-hydroxy-beta-methyl butyrate (HMB, a product of leucine catabolism) has been described. A [2H6]HMB internal standard was added to plasma and standards, and samples were extracted with diethyl ether, backextracted into neutral phosphate, dried, and derivatized for gas chromatography and mass spectrometry. The natural HMB was monitored at 175 amu and the deuterated HMB was monitored at 181 amu. Standard curves were linear to at least 25 microns and were quantitatively recovered from plasma. Basal concentrations of plasma HMB were from 1 to 2 microM in sheep and increased three- to fourfold when leucine's alpha-ketoacid (alpha-ketoisocaproate, KIC) was fed to lambs. This method can also be adapted to quantitate KIC and other branched chain ketoacids in plasma during the same run. PMID- 2221359 TI - A rapid, high resolution DNA sequencing gel system. AB - We have developed a simple method which significantly increases the efficiency of manual DNA sequencing. This method increases both the ease of gel preparation and the quality of fragment resolution. Our system involves (i) casting of gels horizontally, without sealing around the plates; (ii) the use of a self-forming buffer gradient to stack bands in the lower part of the gel; (iii) separation of the samples on two 0.2-mm-thick acrylamide gels (4.5 and 4%) with overlapping readings; (iv) "nonsmiling" electrophoresis with very simple, self-made electrophoresis stands; and (v) prior to exposure in situ dry fixation of the gel matrix to the glass support without previous covalent binding of the gel. On average, we are able to read from nucleotide position 50 to position 600 without ambiguity. PMID- 2221360 TI - Analysis of mucin-derived oligosaccharides by medium-pressure gel-permeation and amino-plate thin-layer chromatography conducted in conjunction. AB - Oligosaccharides present in mucin were labeled by reduction with NaB3H4 and separated by gel-permeation chromatography with a Toyopearl HW-40S column using 0.1 M pyridine acetate, pH 5.0, as the solvent. Each fraction was further analyzed by thin-layer chromatography (TLC) on a Funagel AMP plate, a glass plate precoated with 3-aminopropyl-bonded silica. Acetonitrile/10 mM triethylamine acetate (3/2, by volume) served as the solvent. The sites of oligosaccharides on the TLC plate could be determined according to size, anionic charge, and sugar composition. They could thus be "mapped" on the plate. In this manner, the distribution of oligosaccharides on bovine submaxillary mucin and rat gastric mucin was determined. Each radiolabeled oligosaccharide in newly synthesized rat gastric mucin, metabolically labeled with [14C]glucosamine or [35S]sulfate, was also identified by this method. PMID- 2221362 TI - Extraction method for preparing pyridylamino sugar derivatives and application to porcine gastric mucus glycoprotein analysis. AB - For the sensitive detection of free sugars and oligosaccharides, the use of their pyridylamino derivatives has now found general acceptance. To remove excess 2 aminopyridine from this derivative in a reaction mixture, gel filtration and ion exchange chromatography were conducted. It was found in the present study that contaminated 2-aminopyridine could be selectively removed from the reaction mixture by adjusting the pH with saturated sodium bicarbonate at above 8.5 followed by extraction with benzene. By using this method, fewer purification steps and less time are required, with minimum loss of pyridylamino sugar derivatives. PMID- 2221361 TI - High-pressure liquid chromatography of sialic acids on a pellicular resin anion exchange column with pulsed amperometric detection: a comparison with six other systems. AB - A wide variety of different sialic acids have been reported in nature. Following their release and purification, detection and quantitation of these molecules is now possible by a number of techniques. We and others have previously reported high-pressure liquid chromatography separation of sialic acids with several different columns, elution methods, and detection techniques. We report here a new method for the separation of sialic acids at neutral pH on a Carbopac PA-1 anion-exchange column of pellicular resin, with pulsed amperometric detection following postcolumn addition of alkali. The major advantages of this system are the separation of a variety of sialic acids, sensitive detection (into the picomole range), and the relative ease of use for preparative purposes. Using a set of defined sialic acid standards, this method is compared and contrasted with six other HPLC methods previously described by us and by others. The advantages and disadvantages of each system are also addressed. In the final analysis, no single method is adequate to completely separate and quantitate all of the known sialic acids. However, used in appropriate combinations, these methods allow exploration of the biology of sialic acids in a manner heretofore not possible. PMID- 2221363 TI - Isolation of proteoglycans using phenol extraction and isopycnic centrifugation in cesium trifluoroacetate. AB - A procedure for the rapid isolation of heparan sulfate proteoglycans from Zwittergent lysates of cultured cells and cetylpyridinium precipitates of culture medium is described. After removal of most nonglycosylated proteins by phenol extraction, the proteoglycans are fractionated and isolated by isopycnic sedimentation in cesium trifluoroacetate gradients. The density-isolated proteoglycans, which are largely free of high molecular weight DNA, RNA, and nonglycosylated proteins, are readily amenable to chemical and enzymatic characterization. These procedures, which are designed for efficient and rapid isolation of lipophilic proteoglycans, also appear applicable to the isolation of other high density proteoglycans. PMID- 2221364 TI - Affinity chromatography of DNA fragments and P-modified oligonucleotides. AB - The wide possibilities for use of affinity chromatography are demonstrated by two examples: (i) isolation of a single-stranded fragment of the tick-borne encephalitis virus DNA (302-mer) and an oligonucleotide (34 bases) from reaction mixtures and (ii) fractionation of mixtures of diastereoisomers of octathymidylates with modified internucleotide phosphates. All affinity sorbents are constructed by the covalent attachment of the oligonucleotides to solid supports and can be used repeatedly. PMID- 2221365 TI - A spectrophotometric method for simultaneous determination of protein-bound hexoses and fucose with a mixture of L-cysteine and phenol. AB - A very suitable spectrophotometric method for simultaneous determination of protein-bound hexoses and fucose is presented. A mixture of L-cysteine and phenol in sulfuric acid was used as reagent, whereas absorption measurements were carried out at two wavelengths, namely at 398 nm for fucose and 490 nm for hexoses determination. Optimum conditions for the application of the method were established, special attention being paid to the possible interference of fucose determination with that of hexoses, and vice versa. The proposed method was applied to the determination of hexoses and fucose in serum glycoproteins and seromucoids. The method was found to be very practical enabling a simultaneous determination of both kinds of carbohydrates; moreover, it was proved to be more sensitive and specific in comparison with methods commonly used for individual determination of fucose with L-cysteine and hexoses with phenol. PMID- 2221366 TI - A modified tetramethylbenzidine method for measuring lipid hydroperoxides. AB - A simple and sensitive spectrophotometric method for measuring lipid peroxides and peroxides in general is described. The method was developed by modifying an existing method based on the peroxidase activity of hemoglobin with tetramethylbenzidine as the electron donor. The modifications resulted in much improved sensitivity and reproducibility. With the modified method lipid peroxides as low as 2 nmol can be measured, a high sensitivity compared with other spectrophotometric methods. The absorbance is linear over a wide range of concentrations. It is suggested that this modified method in combination with the commonly used thiobarbituric acid method will give a better quantitation of lipid peroxidation. PMID- 2221368 TI - Gangliosides noncovalently bound to DEAE-Sephadex: application to purification of anti-ganglioside antibodies. AB - A simple, rapid, effective, and inexpensive method for the purification of ligands having high affinity for gangliosides has been developed. DEAE-Sephadex has a high capacity for binding gangliosides (approx 1/1.6, w/w). The gangliosides, bound to the support by electrostatic and hydrophobic interactions, showed a high resistance, in an aqueous environment, to being detached by eluants commonly employed to desorb ligands (i.e., low or high pH or chaotropic agent solutions) or by nonionic detergent solutions as well as by organic solvents. The DEAE-Sephadex-ganglioside complex was assayed as an immunoadsorbent for purifying anti-GM1 ganglioside antibodies from serum of an immunized rabbit. The specific activity of the purified antibodies was 200- to 400-fold higher, and the recovery of the anti-ganglioside activity was above 50%, with respect to the untreated antiserum. The preparation of the complex and the purification of the antibodies can be done in less than 5 h. The glycolipids from the complex can be recovered by elution with organic solvents containing salt or volatile base solutions, and reused. In principle, this method can be adapted for other anionic amphipathic receptor molecules to purify ligands which bind to them. PMID- 2221367 TI - A methodology for determination of phospholipids. AB - A simple method for the determination of phospholipids in an aqueous dispersion and in amniotic fluid was developed. The procedure is based on the observation that dispersed phospholipids promoted the solubilization of an insoluble dye- detergent complex. The solubilization of the complex between the negatively charged dye, Coomassie brilliant blue (CBB), and a positively charged detergent, cetyltrimethylammonium bromide (CTAB), produced a blue solution having a visible absorbance maximum above 600 nm. A linear increase in absorbance intensity occurs with an increase in phospholipid concentration. An assay using the CBB-CTAB reagent adsorbed on 3-mm glass beads is used to estimate total dispersed phospholipids between 2 and 25 micrograms/ml. Thereby, a two-phase water-methanol chloroform system is formed. The products of zwitterionic phospholipids (such as phosphatidylcholine and phosphatidylethanolamine) partition to the organic phase while the dye complex solubilized in anionic phospholipids (such as phosphatidylglycerol and phosphatidylinositol) partitions to the aqueous phase. This procedure results in a convenient, sensitive, and rapid method for the simultaneous determination of the total phospholipid, zwitterionic phospholipid, and anionic phospholipid concentrations. Application of the new assay for determination of phospholipids in amniotic fluid is described. PMID- 2221369 TI - A kinetic method for determination of free vanadium(IV) and (V) at trace level concentrations. AB - A kinetic method based on alkaline phosphatase has been developed to measure free trace levels of vanadium(IV) and (V). The method involves measuring the rate of the alkaline phosphatase-catalyzed hydrolysis of p-nitrophenyl phosphate with (Vi) and without (Vo) a competitive inhibitor in the assay. Michaelis-Menten kinetics for a competitive inhibitor was used to express the relationship between Vo/Vi and the inhibitor concentration. Measuring both Vo and Vi thus yields a Vo/Vi ratio that allows calculation of the competitive inhibitor concentration. Determination of free vanadium in complex fluids can be accomplished by comparing the ratio of rates of p-nitrophenyl phosphate hydrolysis with and without a sequestering agent to the ratios of rates measured on addition of a known vanadium concentration. Free vanadium(V) can conveniently be measured from 10(-7) to 10(-5) M and free vanadium(IV) can be measured at 10(-8) M and above. The error limits on the vanadium determinations range from +/- 3 to +/- 12% of the concentration under investigation depending on the conditions under which the assay was conducted. PMID- 2221370 TI - Method for rapid separation of liposome-associated doxorubicin from free doxorubicin in plasma. AB - To understand and predict the efficacy and/or toxicity of liposomal drugs in vivo, it is essential to have rapid, reliable methods of separating and quantitating both the free and the liposomal forms of the drug. A method using solid-phase extraction chromatography columns was developed to separate and quantitate unencapsulated doxorubicin and liposome-associated doxorubicin in plasma following the intravenous injection of liposomal doxorubicin. The method facilitated the recovery and quantitation of free and liposomal drug. The separation and recovery of doxorubicin were linear across the entire range of possible mixtures (0 to 100%) of the two forms of the drug in plasma. Free drug and liposomal drug were readily separated for liposomal doxorubicin systems varying in size (0.1-1.0 microns) and lipid composition (egg yolk phosphatidylcholine/cholesterol and distearylphosphatidylcholine/cholesterol). The method is rapid and allows for multiple samples to be processed simultaneously. PMID- 2221371 TI - Optimization of immobilized enzyme hydrolysis combined with high-performance liquid chromatography/thermospray mass spectrometry for the determination of neuropeptides. AB - Peptidases, including chymotrypsin, thermolysin, trypsin, V8 protease, and carboxypeptidases A, B, and Y, were immobilized for use in conjunction with HPLC/thermospray MS for the analysis of neuropeptides. The optimal operating conditions for each immobilized enzyme bioreactor were determined. Optimal hydrolysis usually occurred at the highest percentage of aqueous solution in the mobile phase at pH 7-8 and 40-50 degrees C. Often post-HPLC column addition of aqueous solutions before the bioreactor could improve activity and thermospray sensitivity without changing the HPLC separation. Enzymatic hydrolysis requirements were compatible under conditions for HPLC separation and thermospray MS detection of the selected neuropeptides. Synthetic alpha-, beta-, and gamma endorphins were the primary neuropeptides used to evaluate on-line immobilized enzyme bioreactor/MS. HPLC followed by peptidase hydrolysis produced characteristic hydrolysis products for confirming the peptides' identity using thermospray MS detection. Furthermore, the peptide formed from enzymatic hydrolysis resulted in a MS ion current 10-40 times higher than that of the [M + 2H]2+ ion for unhydrolyzed beta-endorphin. The increased sensitivity achieved for detecting the hydrolysis products permits detection and quantitation of synthetic peptides down to 800 fmol. PMID- 2221372 TI - A solid phase assay for the protease of human immunodeficiency virus. AB - A solid phase assay for human immunodeficiency virus (HIV) protease using an immobilized substrate, Affi Gel 10-Gly-Gly-Gly-Gly-Val-Ser-Gln-Asn-Tyr-Pro-Ile Val-Gln-[3H]Gly-OH has been devised. The Tyr-Pro bond of the substrate was hydrolyzed by the protease, releasing the radiolabeled cleavage product, Pro-Ile Val-Gln-[3H]Gly-OH, into the supernatant. The pH optimum was found to be 6.0, and a high ionic strength was required for maximal activity. The solid phase assay is usable for convenient monitoring of purification procedures, and rapid screening of inhibitors of HIV protease. PMID- 2221373 TI - pH and buffering in the bicinchoninic acid (4,4'-dicarboxy-2,2'-biquinoline) protein assay. AB - The HCO3/CO3(2-) buffer used in the bicinchoninic acid (BCA) protein assay has only weak buffering capacity at the recommended pH (11.25). Consequently the assay is rather sensitive to interference from effectively acid or alkaline samples, particularly in the micro method. Adjustment of pH in these alkaline solutions of high [Na+] is complicated by Na+ errors on the pH electrode. Hence it is recommended to prepare the buffers from known amounts of NaHCO3 and Na2CO3, and to reduce the pH to around 10.7; this offers much better buffering capacity with only a limited reduction in color development. PMID- 2221374 TI - Nonradioactive ligand binding assay for epidermal growth factor receptor. AB - A rapid and sensitive nonradioactive ligand binding assay for identifying the agonists and antagonists of epidermal growth factor receptor is described. The assay is easy to perform, has a within-assay error of less than 15%, and does not use radioactive substances. Nonspecific binding is less than 10% and the assay is sensitive enough to detect epidermal growth factor (EGF) antagonists at as little as 10 nM, if the antagonist has the same affinity as EGF. The assay is carried out in 96-well plates and is particularly suitable for large-scale screening. This report includes description of the methods that we used to assess the validity of the assay system, and the results of that assessment. PMID- 2221375 TI - Deletion mutagenesis in M13 by polymerase chain reaction using universal sequencing primers. AB - A simple procedure is described for the efficient deletion of large DNA sequences. The method involves a combination of oligonucleotide-directed mutagenesis in bacteriophage M13 and amplification of the mutagenized product by polymerase chain reaction. In contrast to other protocols employing polymerase chain reaction, synthesis of only one specific primer is required. The efficiency of heteroduplex formation between mutagenic primers directing large deletions and single-stranded template is discussed. PMID- 2221376 TI - Parameterization of contribution of sugar units to elution volumes in reverse phase HPLC of 2-pyridylaminated oligosaccharides. AB - The reverse-phase high-performance liquid chromatography elution data, expressed in glucose units, of 2-pyridylaminated oligosaccharides (PA-oligosaccharides) originated from N-glycosides of glycoproteins have been analyzed with multiple regression to obtain parameters of contribution ascribable to each monosaccharide unit. For the best results, the known PA-oligosaccharides were classified into M series (the "high mannose" type), X-series (those containing xylose), F-series (those containing L-Fuc alpha (1,6)GlcNAc-PA), and Z-series (all others). Within each series, a variable ("unit contribution") is assigned to every sugar component in the oligosaccharide, and the elution value of a given oligosaccharide was assumed to be the sum total of the unit contributions. The unit contribution obtained from such multiple regression calculations led to a set of elution values for oligosaccharides in each series, which showed very good agreement with the observed elution values. These unit contribution values are useful in predicting the elution value when the exact structure is known, and they also aid in predicting the structure from the known elution value. PMID- 2221377 TI - Detection of lipopolysaccharides blotted to polyvinylidene difluoride membranes. AB - Bacterial lipopolysaccharide (LPS) blotted to polyvinylidene difluoride (PVDF) membranes was detected by a technique adapted from current methodologies used to detect glycoproteins. PVDF-bound LPS was coupled to a hapten and localized on the membrane by Western blotting with an antibody-alkaline phosphatase conjugate specific for the hapten. Immobilon blots could be made reversibly transparent for photography and densitometry. PMID- 2221378 TI - Separation of phycobiliprotein subunits by reverse-phase high-pressure liquid chromatography. AB - Baseline separation of subunits of diverse phycobiliproteins was achieved by a reverse-phase HPLC gradient method with a C4 large-pore column and a solvent system consisting of 0.1% trifluoroacetic acid (TFA) in water and 0.1% TFA in 2:1 (v/v) acetonitrile:isopropanol. The procedure was successfully applied to cyanobacterial allophycocyanin and C-phycocyanins, an unusual phycocyanin from a marine cyanobacterium, red algal B- and R-phycoerythrins, and a cryptomonad phycoerythrin. The subunit sizes in these proteins range from about 7.5 to 30 kDa. Sample recovery was in excess of 85% in all cases. On-line spectroscopic analysis with a multiple diode array detector allowed determination of the type and number of bilins carried by each subunit. PMID- 2221379 TI - Automation of a chloramphenicol acetyltransferase assay. AB - Accurate quantification of chloramphenicol acetyltransferase (CAT) enzyme activity in a large number of samples has been achieved through robotization of a CAT assay on a laboratory workstation (Biomek 1000). The basic principle of this CAT assay relies on the selective diffusion of [3H]acetylchloramphenicol into a water-immiscible liquid scintillation cocktail. This methodology gives unique characteristics to this robotized protocol by allowing complete control over the kinetics of the CAT enzymatic reaction which is a critical parameter in the CAT assay. Thus it has been possible to optimize the CAT assay for every processed sample, through real time monitoring of the enzymatic reaction, and to achieve maximum accuracy in CAT quantification. Moreover the sensitivity of this automated assay is high (detection threshold; 10(-4) CAT unit), and the sample processing is fast (approximately 125 samples per hour). Compared to other CAT assay protocols currently used, our robotized technique offers major advantages in terms of CAT quantification, and sets new standards for CAT assay productivity. PMID- 2221380 TI - Fluorescence assay for per-cell estimation of cytochrome P-450-dependent monooxygenase activities in keratinocyte suspensions and cultures. AB - An assay was characterized that facilitated per-cell estimation of cytochrome P 450-dependent monooxygenase activities in whole-cell suspensions and cultures of murine epidermal keratinocytes (MEKs). 7-Ethoxycoumarin O-deethylase (7-ECD), 7 ethoxyresorufin O-deethylase (7-ERD), and 7-pentoxyresorufin O-deethylase (7-PRD) activities were monitored by fluorescent detection of their products. MEKs were made permeable by a freeze-thaw cycle, and xenobiotic metabolism occurred in situ. Analyses of cultured MEKs were made with the cells attached to the culture dishes. Product formation was proportional with MEK cell number and assay time and was dependent upon a NADPH-generating system. The three monooxygenase activities were inhibited to various degrees, in a dose-dependent manner, by the P-450 inhibitors alpha-naphthoflavone and metyrapone. The number of MEKs obtained from a single mouse was sufficient for multiple analyses. The assay was also used to determine monooxygenase activities in whole-cell suspensions of rat hepatocytes. Constitutive per hepatocyte 7-ECD, 7-PRD, and 7-ERD activities were 357-, 96-, and 1926-fold greater, respectively, than the activities measured in suspensions of dorsal MEKs. PMID- 2221381 TI - Flow injection analysis of serum urea using urease covalently immobilized on 2 fluoro-1-methylpyridinium salt-activated fractogel and fluorescence detection. AB - Serum samples were analyzed for their urea content using fluorescence flow injection analysis incorporating an immobilized urease bioreactor and a gas permeable separator. The urease was immobilized under mild and facile conditions to a hydrophilic 2-fluoro-1-methylpyridinium-activated support. The ammonia released as a result of urease-catalyzed urea hydrolysis diffused through a gas permeable membrane into a constant stream of o-phthaldehyde solution to form a highly fluorescent product with lambda ex at 340 nm and lambda em at 455 nm. Up to 25 serum samples can be analyzed per hour. The within-day coefficient of variation (CV) was 1.12% and the day-to-day CV was 1.25% for serum containing 10.50 mg urea nitrogen dl-1. The bioreactor shows excellent storage (at 4 degrees C) and operational stabilities (at 37 degrees C). PMID- 2221382 TI - Comparison of specific radioactivities of human alpha-lactalbumin iodinated by three different methods. AB - Radioiodination provides an extremely sensitive method for the detection of low levels of proteins. In the development of a sensitive radioimmunoassay for human alpha-lactalbumin (alpha-LA), the protein was labeled to high specific activity (approaching 2000 Ci/mmol) with lactoperoxidase, chloramine-T, and Iodogen. Despite high specific activities of the labeled protein by each method, there was a considerable difference in their binding affinity with monoclonal anti-human alpha-LA antibodies due to varying degrees of protein damage. Iodination of human alpha-LA with Iodogen resulted in labels of the highest specific activity and immunoreactivity with the monoclonal antibodies used. PMID- 2221383 TI - Nonradioactive labeling of probe with digoxigenin by polymerase chain reaction. AB - Probes nonradioactively labeled with the steroid hapten digoxigenin have several intriguing properties, including a high sensitivity equivalent to that of radioactive probes, speed in detection, low hazard potential in handling, and possibility of long-term storage. The use of polymerase chain reaction for labeling probe has been demonstrated to offer various advantages including efficient labeling of fragments as small as 100 bp, direct labeling of genomic DNA, and labeling with subnanogram amounts of input DNA. We therefore investigated whether this technique could be adapted for labeling with a relatively large molecule such as digoxigenin. In this report, we show that the polymerase chain reaction is a very efficient technique for synthesis of digoxigenin-labeled DNA and we present an extremely simple procedure for purification of the non-isotopically labeled fragments. PMID- 2221385 TI - Microscale, filtration-type binding assay for studying myosin-erythrocyte protein 4.1 interactions. AB - In vitro binding of skeletal muscle myosin and the erythrocyte cytoskeleton linker protein, band 4.1, was evaluated in a novel small-volume, filtration-based binding assay. The assay equipment consisted of a plastic grid containing several buffer-filled wells into which were placed small nylon screens. Myosin was covalently tethered to an agarose (Sepharose) support and aliquots of this resin were pipetted onto the surface of the submerged nylon screen. Following addition of radiolabeled protein 4.1, and an appropriate incubation period, the myosin Sepharose beads and bound protein 4.1 were separated by wicking the buffer from beneath the nylon screen with a piece of filter paper. Nylon screens, with adherent resin beads, and the filter paper wicks were then counted to give the amounts of bound and free protein 4.1, respectively. This system proved to be a rapid, simple, and quantitative method for evaluating the behavior of a myosin binding protein under conditions in which free myosin would be prone to assemble into filaments. Moreover, since the assay separates bound and free components within a few seconds, it is well suited for the analysis of low-affinity interactions. PMID- 2221384 TI - Simultaneous isolation of DNA, RNA, and antigenic protein exhibiting kinase activity from small tumor samples using guanidine isothiocyanate. AB - Correlative studies of genes and their expression in human tumors are often hampered by the small sample size and the need to use differing and incompatible techniques to obtain DNA, RNA, and protein. We describe an extension of the established guanidine isothiocyanate method for isolation of DNA and RNA which allows the simultaneous isolation of total cellular protein. The protein obtained by this method (from solid tumors and cell lines) was comparable to protein extracted by a standard detergent solubilization method. Antigenicity was retained as demonstrated by Western blotting for epidermal growth factor receptor and actin and by immunoprecipitation of p53. Kinase activity was similar in proteins extracted by the two methods. It seems probable that most monomeric proteins can be obtained in a form suitable for Western analysis and immunoprecipitation and that these may also retain some functional activity. PMID- 2221386 TI - A procedure for making simultaneous determinations of the relative levels of gene transcripts in tissues or cells. AB - In this paper, we describe a method for making simultaneous determinations of the relative levels of selected resident gene transcripts in biological samples. The procedure consists of immobilizing a battery of cloned genes on a nitrocellulose or nylon filter and hybridizing the filter with radiolabeled cDNA synthesized from mRNA extracted from tissue or cell lines. The intensity of the autoradiographic signals obtained from the various genes on the filter is interpreted to be roughly proportional to the relative numbers of transcripts of the genes present in the original mRNA population. The reliability of the method was established by detecting the expression of c-N-ras and c-myc in human promyelocytic HL-60 cells, which are known to express these two oncogenes. The accuracy of the technique was further established by using a conventional method to hybridize filter-bound, cytoplasmic RNA with labeled probes synthesized from plasmid inserts of genes identified by the screening procedure. The utility of the procedure was demonstrated by our ability to simultaneously examine the relative levels of expression of 21 oncogenes in a radiation-induced canine lung carcinoma. PMID- 2221387 TI - Assay of N-myristoyl transferase by selective adsorption of myristoyl-coenzyme A on acidic alumina. AB - We have developed a simple and rapid method for detecting the enzyme myristoyl CoA:protein N-myristoyl transferase. The enzyme catalyzes the transfer of the myristoyl moiety of myristoyl-CoA to the amino-terminal glycine residue of a peptide (protein). Incorporation of the [14C]myristate into the peptide is quantified after separation of the [14C]myristoyl-peptide from unreacted [14C]myristoyl-CoA by selective adsorption of [14C]myristoyl-CoA on acidic alumina. Optimal assay concentrations were 200 microM synthetic peptide, 1 microM [14C]myristoyl-CoA, 10 mM Tris-HCl/1 mM dithiothreitol/0.1 mM ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid/aprotinin (10 micrograms/ml) buffer, pH 7.4, and 1-10 micrograms protein. PMID- 2221388 TI - Determination of sulfhydryl groups and disulfide bonds in a protein by polyacrylamide gel electrophoresis. AB - A general method by polyacrylamide gel electrophoresis for the determination of sulfhydryls and disulfides in a protein was developed. The method included a two step alkylation procedure: the first step consisted of alkylation of the sulfhydryl groups with iodoacetic acid in the presence and absence of 8 M urea; the second step consisted of alkylation of the disulfide groups with iodoacetamide after reduction with a thiol. By high-pH urea gel electrophoresis, all the half-cystine residues in a protein could be categorized into three states: reactive sulfhydryls, nonreactive sulfhydryls, and disulfide bonded. The particular advantage of the method is that the states of half-cystines in different protein species can be analyzed independently both in isolated protein and in biological translation systems. PMID- 2221389 TI - Quantitative analysis of N-sulfated, N-acetylated, and unsubstituted glucosamine amino groups in heparin and related polysaccharides. AB - A colorimetric procedure for quantitative determination of free and substituted glucosamine amino groups in heparin and related polysaccharides has been developed. The total content of hexosamine amino groups is determined by a modification of the method of Tsuji et al. (1969, Chem. Pharm. Bull. 17, 1505 1510); this method involves acid hydrolysis under conditions effecting complete removal of N-acetyl and N-sulfate groups, deaminative cleavage with nitrous acid, and colorimetric analysis of the resultant anhydromannose residues by reaction with 3-methyl-2-benzothiazolinone hydrazone (MBTH). N-sulfated glucosamine residues are cleaved selectively by treatment with nitrous acid at pH approximately 1.5 (J. E. Shively, and H.E. Conrad, 1976, Biochemistry 15, 3932 3942) and quantitated by the MBTH reaction. Under carefully controlled conditions, deamination at pH approximately 1.5 is highly specific for N-sulfated glucosamine residues, but an excess of reagent causes some cleavage of residues with unsubstituted amino groups as well. Deaminative cleavage at pH approximately 4.5 results in preferential degradation of unsubstituted glucosamine residues, but some cleavage (5-8%) of N-sulfated residues also occurs. However, analysis of the content of N-sulfated residues by the specific pH 1.5 procedure allows appropriate corrections to be made. From the value for total hexosamine content and the sum of N-sulfated and unsubstituted residues, the content of N-acetylated residues is calculated by difference. The modified deamination procedures, in combination with product analysis by the MBTH reaction, have been applied to several problems commonly encountered in the analysis and characterization of heparin. PMID- 2221390 TI - Reversed-phase liquid chromatographic separation of juvenile hormone and its metabolites, and its application for an in vivo juvenile hormone catabolism study in Manduca sexta. AB - A convenient reversed-phase liquid chromatographic method was developed to separate juvenile hormone (JH) and its metabolites. The known metabolites including JH acid, JH diol, and JH acid-diol, as well as an unknown metabolite, were efficiently separated within 25 min on a 50 X 4.6 mm polymer column using a linear gradient of acetonitrile:5 mM Hepes (pH 7.4) buffer. Use of the polymer column diminished tailing observed for the diol metabolite on a C18 silica column, and allowed use of slightly basic buffers without concern of column instability. Use of buffer was essential to give good peak shape and reproducible retention behavior for the acidic metabolites. Using this method, an in vivo JH catabolism study was performed in fifth stadium larvae of Manduca sexta. Injected (10R)-[3H]JH III was rapidly converted to JH acid-diol and to an unknown compound(s) indicating that, in addition to JH esterase, epoxide hydrolase and other reactions play an important role in the catabolism of JH. PMID- 2221391 TI - High-performance liquid chromatographic separation of hyaluronan and four proteoglycans produced by human bone cell cultures. AB - Four proteoglycans and hyaluronan synthesized by cultured human bone cells were isolated using a two-step high-performance liquid chromatography system involving desalting and buffer exchange with a TSK-GEL HW 40(S) column followed by ion exchange separation on a Nucleogen 4000-10 DEAE column. The desalting of 4 M guanidinium HCl extracts by a TSK-GEL HW 40(S) column equilibrated in a formamide:KH2PO4 buffer produces greater than 95% recoveries, enables quantitation of label incorporation and requires only 40 min to complete. The Nucleogen 4000-10 DEAE column utilizes the same buffer system and requires only 100 min for the resolution of four distinct types of proteoglycans. The formamide:KH2PO4 buffer system is compatible with a previously developed polyacrylamide gel system for the electrophoretic profiling of proteoglycans. After separation by charge density, proteoglycans were further resolved by size distribution using a calibrated TSK-GEL HW 75(F) column which also enabled the estimation of the apparent Mr of hyaluronan produced by the bone cells. The same TSK-GEL HW 40(S) resin is used to exchange pooled proteoglycans into buffers for analyzing enzyme digests of glycosaminoglycan chains and core proteins. The technique has been applied to the analysis of biosynthetically labeled proteoglycans produced in culture by fetal and adult human bone cells. A distinct pattern of proteoglycan size and secretion for both cell types could be shown using this method. The method of analysis is useful for high yield and rapid screening of various cell types for both biosynthetic rate studies and analysis of patterns of proteoglycan synthesis. PMID- 2221392 TI - A radiometric assay for HIV-1 protease. AB - A rapid, high-throughput radiometric assay for HIV-1 protease has been developed using ion-exchange chromatography performed in 96-well filtration plates. The assay monitors the activity of the HIV-1 protease on the radiolabeled form of a heptapeptide substrate, [tyrosyl-3,5-3H]Ac-Ser-Gln-Asn-Tyr-Pro-Val-Val-NH2, which is based on the p17-p24 cleavage site found in the viral polyprotein substrate Pr55gag. Specific cleavage of this uncharged heptapeptide substrate by HIV-1 protease releases the anionic product [tyrosyl-3,5-3H]Ac-Ser-Gln-Asn-Tyr, which is retained upon minicolumns of the anion-exchange resin AG1-X8. Protease activity is determined from the recovery of this radiolabeled product following elution with formic acid. This facile and highly sensitive assay may be utilized for steady-state kinetic analysis of the protease, for measurements of enzyme activity during its purification, and as a routine assay for the evaluation of protease inhibitors from natural product or synthetic sources. PMID- 2221393 TI - A gas chromatographic-mass spectrometric technique for studying simultaneous hydrogen-deuteron exchange and para-orthohydrogen conversion in hydrogenases of Desulfovibrio vulgaris Hildenborough. AB - An original gas chromatographic-mass spectrometric technique is described for studying simultaneous dihydrogen-deuteron exchange and para-ortho H2 conversion catalyzed by different Desulfovibrio hydrogenases. Para and orthohydrogens are separated on an alumina column at the temperature of liquid nitrogen, but if both HD and ortho H2 are present, their retention times are too close to each other for total separation and only one peak is observed with a thermal conductivity detector. In order to resolve the peaks from one another, a fraction of the gas released from the gas chromatograph column is admitted to the ion source of a mass spectrometer, where the gases are separated according to their respective masses. Because of a peak-jumping system, the different components involved in the exchange and in the conversion reactions can be scanned so that the spectra corresponding to mass m/e 2 (para and ortho H2), m/e 3 (HD), and m/e 4 (D2) can be obtained simultaneously. This technique has been employed to resolve a controversial problem concerning the occurrence or lack of any para-orthohydrogen conversion in heavy water. Actually both exchange and conversion were demonstrated to occur with a (NiFe) hydrogenase, whereas with a (NiFeSe) hydrogenase, which had an exchange activity equivalent to that of the former, practically no para-ortho conversion could be observed in D2O. These findings are related to the constitutional and catalytic properties of the hydrogenases belonging to the different classes. PMID- 2221394 TI - Analysis of inositol by high-performance liquid chromatography. AB - A high-performance liquid chromatographic (HPLC) method has been developed for identification and quantification of inositol isomers and monosaccharides in inositol-containing glycans. The method, which can determine 10 pmol of inositol, utilizes an Aminex HPX-87C column packed with an 8% crosslinked cation-exchange resin in the calcium form eluted with deionized water at 50 degrees C. NaOH solution is added to the column effluent through a postcolumn tee to increase the pH (pH greater than 11.6) before entering a pulsed amperometric detector which is highly sensitive for polyhydroxylated compounds. Samples in which inositol is linked to sugar through a glycosidic bond are hydrolyzed with 5.5 N trifluoroacetic acid, 100 degrees C, 4 h, and then reduced with NaBH4. Samples in which inositol is linked via a phosphate ester are hydrolyzed with 6 N HCl, 110 degrees C, 24 h. This method has been applied to the analysis of inositol in the hamster prion proteins (PrP) PrP27-30, and PrPSc. PMID- 2221395 TI - Enhanced spectrofluorimetric determination of the pesticide warfarin by means of the inclusion complex with beta-cyclodextrin. AB - The warfarin-beta-cyclodextrin inclusion complex alters the luminescent properties of warfarin. This feature allows the use of a spectrofluorimetric method for its determination that gives improved analytical performance. The spectral changes associated with the inclusion process allowed a value of 160 l mol-1 to be obtained for the complexation constant. Fluorescence intensity is linearly related to warfarin concentration for a quantification limit of from 0.2 to 4 micrograms ml-1. The relative standard deviation at the 1.5 microgram ml-1 level is 3.5%. The method was applied satisfactorily to the determination of warfarin in irrigation water. PMID- 2221396 TI - Determination of salicylic acid and its metabolites in urine by derivative synchronous spectrofluorimetry. AB - The simultaneous determination of salicylic acid in binary and/or ternary mixtures and its two main urinary metabolites is proposed. Mixtures of salicylic, salicyluric and gentisic acids are resolved by synchronous spectrofluorimetry, in combination with first-derivative measurements. The urine is extracted with diethyl ether in acid medium. Salicylic and salicyluric acids are re-extracted into glycine-sodium hydroxide buffer solution of pH 11.6 and determined at that pH, and salicylic and gentisic acids are re-extracted into boric acid-sodium hydroxide buffer solution of pH 8.5 and determined at pH 6. PMID- 2221397 TI - Bioluminescent flow sensor for the determination of L-(+)-lactate. AB - The amount of L-lactate in biological fluids (serum, plasma and cerebrospinal fluid) was determined by monitoring the reduced form of nicotinamide adenine dinucleotide (NADH) produced by immobilised lactate dehydrogenase (LDH), with bacterial bioluminescent enzymes immobilised on a separate nylon coil. The LDH catalysed the reaction of L-lactate with NAD; this reaction took place in a nylon coil that preceded the coil for the bioluminescent detection. The co immobilisation of alanine aminotransferase (ALT) with LDH improved the lactate transformation by 117-183%. The response was linear from 0.1 to 50 micron mol l( 1) at 25 degrees C for the LDH - ALT reactor. The intra- and inter-assay coefficients of variation were less than 5% and the recoveries ranged from 93 to 106%. The results agreed well with those obtained with a spectrophotometric method and with the normal reference values. PMID- 2221398 TI - Influence of bovine immunoglobulin G on faradaic reactions at electrodes. AB - The effect of bovine immunoglobulin G (IgG), adsorbed on different electrode materials, on faradaic reactions of hexacyanoferrate(III)-hexacyanoferrate(II), hydroquinone-benzoquinone, nicotinamide adenine dinucleotide, reduced from (NADH), and phenol is described and discussed. The reactions are partially inhibited by IgG, but the current and peak potentials reach protein-independent values for higher concentrations of IgG. The hydroquinone-benzoquinone couple can be used for detection purposes at IgG-covered electrodes in electrochemical immunoassays. PMID- 2221399 TI - Determination of 2-methylaziridine in workplace atmospheres. AB - A sampling and analytical procedure was developed for the monitoring of airborne 2-methylaziridine (MA). The analyte is collected by drawing air through a solution of 2,4,6-trinitrobenzenesulphonic acid (TNBS). In situ derivatisation of MA with TNBS during sample collection provides stability to the highly reactive analyte and makes it amenable to a sensitive high-performance liquid chromatographic determination with ultraviolet detection. The purified synthetic derivative of MA with TNBS is more suitable as a calibration standard than commercially available MA. PMID- 2221400 TI - Determination of 1,4-dioxane in cosmetic products by high-performance liquid chromatography. AB - A rapid high-performance liquid chromatographic procedure has been developed for the assay of 1,4-dioxane in cosmetic products. After solid-phase extraction, using Bond Elut CN and Bond Elut C18 cartridges, samples were analysed directly on a LiChrospher CH-8 reversed-phase column with spectrophotometric detection at 200 nm and acetonitrile - water as eluent. Recovery of 1,4-dioxane from different cosmetic matrices was between 81.5 and 90.1% in the 30-90 microgram g(-1) range. The minimum quantifiable amount was 6.5 microgram g(-1). The method is simple, reproducible and specific and is suitable for routine analyses of commercial cosmetics. PMID- 2221401 TI - Determination of non-metallic elements by capacitively coupled helium microwave plasma atomic emission spectrometry with capillary gas chromatography. AB - A capacitively coupled microwave helium plasma with a tubular tantalum electrode was evaluated as an element selective detector for gas chromatography (GC). The end of a 10-m bonded fused capillary column was directly inserted into the tubular electrode without any switching system. A heated copper tube was used to house the part of the GC column that protruded from the oven. The optimisation of operating parameters, line selection, background emission and horizontal and vertical observation position is described. Analytical figures of merit including sensitivity, reproducibility, signal to background ratio, selectivity, dynamic range and limit of detection (LOD), were evaluated for carbon, hydrogen, chlorine and bromine emission. Limits of detection in the low ng range (20 pmol) were obtained for halogenated compounds using carbon emission, whereas LODs in the 0.1 micrograms range (2 nmol) were obtained using chlorine or bromine emission lines. PMID- 2221402 TI - Single-sweep polarography of the copper(II)-3-hydroxy-1-p-sulphonatophenyl-3 phenyltriazene complex and its analytical applications. AB - A polarographic investigation of the copper-3-hydroxy-1-p-sulphonatophenyl-3 phenyltriazene (HSPT) complex in 0.05 M sodium tetraborate medium is described and a simple and sensitive single-sweep polarographic method for the determination of trace amounts of copper in biological samples is proposed. The complex was shown to be Cu(HSPT)2 with log beta' = 11.38. The polarographic wave is caused by the reduction of copper(II) in the adsorbed complex to copper amalgam on the surface of a mercury electrode. The current peak is directly proportional to the concentration of copper in the range 8.0 x 10(-9)-4.0 x 10( 6) M and the detection limit is 5.0 x 10(-9) M. PMID- 2221403 TI - Nitriles and isonitriles as interferents in cyanide determination in polluted waters. AB - The interference of nitriles and isonitriles in cyanide determination was studied using the pyridine-barbituric acid direct spectrophotometric method or the same method after distillation of the sample, a microdiffusion-potentiometric (ion selective electrode) also being used. Phenylacetonitrile, benzonitrile, acrylonitrile, iminodiacetonitrile and acetonitrile were tested as nitriles. Benzyl isocyanide butyl isocyanide and 1-[(isocyanomethyl)sulphonyl]-4 methylbenzene were assayed as isonitriles. It can be concluded that both nitriles and isonitriles should be considered as interferents in all the methods of cyanide determination studied. The level of interference generally increases with the ratio of interfering compound to cyanide and is greatest for low cyanide concentrations. PMID- 2221404 TI - Second-derivative spectrofluorometric determination of sulphoxide impurity in phenothiazine drug substances and formulation. AB - A direct second-derivative spectrofluorimetric procedure for determining sulphoxide impurity in phenothiazines and their formulations has been developed. The method, which has been applied to the analysis of chlorpromazine hydrochloride and prochlorperazine mesylate, as examples of typical phenothiazine substances, and to their formulations, is based on the measurement of the amplitude taken from the minimum at ca. 270 nm to the longer wavelength maximum in the second-derivative excitation spectrum of the sulphoxide in pH 8 buffer solution. The method is rapid, accurate and precise, and can be used to measure the concentration of sulphoxide in phenothiazines and their formulations at concentrations down to 0.1% m/m of that of the parent phenothiazine. PMID- 2221405 TI - Human auditory steady-state response during general anesthesia. AB - The 40-Hz auditory steady-state evoked response (ASSR) is a sinusoidal electrical response of the brain to periodically presented auditory stimuli. It was recorded during anesthesia in 10 elective surgical patients to evaluate its usefulness as a measure of the level of consciousness. The anesthetic agents used were thiopental, fentanyl, and isoflurane with or without nitrous oxide. Recordings were carried out during the period before induction and during induction, surgical anesthesia, emergence, and recovery from anesthesia. The level of consciousness was measured with an auditory stimulus detection task. The electroencephalogram (EEG) was also recorded for comparison with the ASSR. The following indices were analyzed: total EEG power, relative power in the beta, alpha, theta, and delta frequency bands, and the median and spectral edge frequency. The amplitude of the ASSR was reduced significantly at the end of the induction period and decreased below noise levels during surgical anesthesia. It increased significantly during emergence and recovery. The amplitude during recovery remained significantly smaller than the preinduction values. The changes of the ASSR paralleled those of the level of consciousness. The EEG measurements were distorted by the presence of muscle artifacts that were prominent during emergence and recovery. The amplitude of the ASSR appears to provide a more reliable indicator of the level of consciousness than the EEG. PMID- 2221406 TI - Does isoflurane lead to a higher incidence of myocardial infarction and perioperative death than enflurane in coronary artery surgery? A clinical study of 1178 patients. AB - To examine if the choice of volatile agents influences cardiac outcome in coronary artery surgery, 1178 patients undergoing elective coronary artery bypass grafting without additional operations received enflurane (608) or isoflurane (570) as their primary anesthetics. The inspired concentration of volatile agent (administered with 50% nitrous oxide) was adjusted depending on the level of blood pressure at the discretion of the anesthesiologist. In addition to the volatile agent assigned, each patient received small doses of fentanyl at induction and before sternotomy (total 0.006-0.008 mg/kg). The groups did not differ in preoperative and surgical characteristics except for a more frequent history of renal dysfunction in patients given isoflurane. The rates of postoperative myocardial infarction, administration of positive inotropic agents at the time of weaning from cardiopulmonary bypass, and in-hospital deaths in the enflurane and isoflurane groups were 1.8% and 4.0% (P less than 0.05), 4.9% and 8.1% (P less than 0.05%), and 0.3% and 2.1% (P less than 0.01), respectively. Although the mechanism of the adverse effects of isoflurane could not be clarified in this study, these results demonstrate that the use of isoflurane could be inappropriate in patients undergoing coronary artery bypass grafting. PMID- 2221408 TI - Contributions of liver perfusion flow rate and enzyme inhibition to altered verapamil clearance with halothane: a study in the isolated perfused rat liver. AB - Verapamil clearance is reduced during halothane administration. This study evaluated relative contributions of reduced hepatic flow rate and hepatic metabolizing enzyme inhibition by halothane as a cause of reduced verapamil clearance. An isolated perfused rat liver model was utilized in which flow rate could be fixed during halothane administration. Perfusions were performed on five to six livers under each of the following conditions: (a) control--40 mL/min flow rate with no anesthetic exposure; (b) 1.5% halothane--40 mL/min; (c) 2.25% halothane--40 mL/min; (d) reduced flow--20 mL/min with no anesthetic exposure; and (e) reduced flow with 1.5% halothane--20 mL/min. Halothane caused dose dependent decreases in both total hepatic and intrinsic clearance rates (P less than 0.05). With no anesthetic exposure, a flow reduction of 50% (20 mL/min) also gave a large reduction (P less than 0.05) in hepatic clearance of verapamil compared with the control condition (40 mL/min). The addition of 1.5% halothane to the reduced flow condition was not associated with further reduction in hepatic clearance rate. Results of this study suggest that although both reduced hepatic perfusion and hepatic enzymatic inhibition by halothane administration are associated with decreased verapamil clearance, a greater proportion of this decrease appears to be due to reductions in hepatic flow. The present results may apply to other drugs used in anesthesia that have high hepatic extraction ratios; thus, clearance of these drugs may be more dependent on hepatic blood flow than on hepatic enzyme activity. PMID- 2221407 TI - Low-dose almitrine bismesylate enhances hypoxic pulmonary vasoconstriction in closed-chest dogs. AB - The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor response was studied in six closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2; the left lung was ventilated either with 100% O2 ("hyperoxia") or with an hypoxic gas mixture ("hypoxia": end-tidal oxygen tension = 60.3 +/- 0.6 mm Hg). On two consecutive days, each dog received either almitrine (Vectarion, Servier Lab) or malic acid. Consecutive almitrine doses of 0.003, 0.03, 0.3, and 3.0 micrograms.kg-1.min-1, or the equivalent volumes of malic acid without almitrine, were administered intravenously as a constant peripheral infusion for 15 min. Percent blood flow to each lung was calculated based on a variation of the traditional shunt equation. The change in percent left lung blood flow (delta %QL VA) increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. The change in arterial oxygen tension (delta PaO2) also increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. It is concluded that in dogs low-dose almitrine enhances hypoxic pulmonary vasoconstriction and that this enhancement is dose related. PMID- 2221409 TI - Hemodynamic effects of diltiazem during vasoconstrictor pulmonary hypertension in sheep. AB - Calcium channel blockers have been effective as pulmonary vasodilators in patients with pulmonary hypertension. The current study therefore compared the effects of prostaglandin E1, an effective pulmonary vasodilator, with the effects of the water-soluble calcium channel blocker diltiazem during pulmonary hypertension in sheep. Pulmonary hypertension was produced by continuous intravenous administration of U46619 to halothane-anesthetized sheep. Prostaglandin E1 decreased pulmonary artery pressure 29%, decreased pulmonary vascular resistance (Rp) 57%, and did not affect the ratio of pulmonary to systemic vascular resistance (Rp/Rs). Diltiazem decreased pulmonary artery pressure 15%, decreased Rp 50%, and did not affect Rp/Rs. When 0.33 mL/kg polyethylene glycol-ethanol vehicle (the vehicle used for nifedipine administration in a prior study) was administered during diltiazem infusion, pulmonary artery pressure increased 19%, Rp increased 72%, and Rp/Rs increased 29%. These results indicate that diltiazem is an effective pulmonary vasodilator and suggest that the previously reported unfavorable results of nifedipine may have been due to the vehicle used for nifedipine administration. PMID- 2221410 TI - Changes in cerebral blood flow velocity after release of intraoperative tourniquets in humans: a transcranial Doppler study. AB - The effect of release of intraoperative thigh tourniquets on velocity of blood flow in the middle cerebral artery was examined in five patients given general anesthesia with controlled ventilation for lower extremity orthopedic procedures using transcranial Doppler sonography. Middle cerebral artery blood flow velocity increased significantly from 52 +/- 6 (SEM) to 82 +/- 24 cm/s (an increase of 58% +/- 13%) within 4 +/- 1 min after tourniquet release and remained significantly elevated for 7 min. A positive linear correlation was found between middle cerebral artery blood flow velocity and PETCO2 on each occasion (0.97 greater than or equal to r greater than or equal to 0.84, 0.001 greater than P greater than 0.0001) after tourniquet deflation. Assuming a linear relationship between flow velocity and flow, these findings suggest that significant increase in cerebral blood flow can occur after intraoperative tourniquet release and that this increase appears to be mostly CO2-dependent. PMID- 2221411 TI - Comparison of propofol and thiopental/halothane for short-duration ENT surgical procedures in children. AB - Experiences with propofol in pediatric anesthesia are limited. We undertook a study to evaluate the quality of induction and recovery from anesthesia with propofol compared to thiopental/halothane. Twenty children received 3 mg.kg-1.min 1 of propofol as a loading dose followed by a maintenance dose of 0.1 mg.kg-1.min 1 (+/- 10%). Twenty children received 5-7 mg/kg of thiopental, and maintenance was provided with halothane (0.5%-1.5%). The interval between the end of the administration of propofol or thiopental/halothane and extubation, as well to discharge to the ward, was significantly shorter with propofol (4.4 versus 13.5 min and 7.22 versus 30.4 min, respectively). Spontaneous movements and pain on injection were seen significantly more frequently with propofol, whereas laryngospasm and hiccup were only observed with thiopental. During the first 6 h after the surgical procedure, analgesics were needed significantly more often in the thiopental group. Nausea and vomiting also were observed more frequently in the thiopental group. In conclusion, propofol used as a single anesthetic is a satisfactory technique for ENT surgery of short duration in children. PMID- 2221412 TI - Preoxygenation in the elderly: a comparison of the four-maximal-breath and three minute techniques. AB - To compare the effectiveness of two routinely used methods of preoxygenation in protecting against hypoxia in the elderly, the arterial O2 saturation was measured using an oximeter. Twenty-four elderly patients (greater than or equal to 65 yr) presenting for elective orthopedic surgery were randomly allocated to receive either 3-min or four-maximal-breaths of 100% O2 via a Bain circuit. After preoxygenation, anesthesia was induced, tracheal intubation performed with patients kept apneic, and the endotracheal tube left open to air. The arterial O2 saturation was measured before preoxygenation and continually recorded during desaturation. Although attaining similar arterial O2 saturation values after preoxygenation, patients in the four-maximal-breath group had significantly shorter times (P less than 0.0001) to all levels of desaturation. We suggest that preoxygenation with 3-min breathing of 100% O2 offers more protection against hypoxia due to prolonged apnea after induction of anesthesia in the elderly than does four maximal breaths of 100% O2. PMID- 2221413 TI - Cardioprotective effects of carnitine in extensive aortocoronary bypass grafting: a double-blind, randomized, placebo-controlled clinical trial. AB - The cardioprotective effects of carnitine were tested in patients undergoing multiple aortocoronary bypass grafting. Intermittent aortic cross-clamping at 28 degrees C was used. Mean total cross-clamping time was 30 +/- 11 min. Patients were randomized into three groups: a control group receiving placebo (group 1), a group pretreated with 3 g carnitine intravenously before cardiopulmonary bypass (CPB) (group 2), and a group pretreated with 6 g carnitine intravenously (group 3). The markers of myocardial ischemia included levels of adenosine triphosphate, its catabolites, and creatine phosphate in transmural left ventricular biopsy specimens taken at the beginning and end of CPB, as well as hemodynamic recovery during weaning from CPB and for the next 24 h. The intravenous infusion of carnitine (3 or 6 g) had no hemodynamic effect. At the end of CPB myocardial tissue levels of adenosine triphosphate and creatine phosphate did not differ significantly among the groups (P greater than 0.05). Recovery of cardiac function during weaning from CPB and for the following 24 h was similar in all three groups (P greater than 0.05). It is concluded that pretreatment with carnitine neither facilitates weaning from cardiopulmonary bypass in patients undergoing aortocoronary bypass surgery nor favorably affects hemodynamic function during the next 24 h. PMID- 2221414 TI - A rabbit model for evaluation of spinal anesthesia: chronic cannulation of the subarachnoid space. AB - A rabbit model for evaluation of spinal anesthesia is presented. Chronic cannulation of the subarachnoid space was performed in 44 rabbits using the translumbar approach. An autopsy was performed 24 h after the operation on four of the animals. Intrathecal injections of methylene blue did not reveal any leakage from the spinal space. X-ray examination performed on the second and 30th days after the implantation indicated free spread of the injected solution in the subarachnoid space without any obstruction. Repeated injections of four identical doses of bupivacaine at 3-day intervals showed reproducible pharmacologic effects. Administration of different doses of the anesthetic produced a clear dose-response relationship. The relative activity of the anesthetic agents was found to be identical to that previously obtained in humans. No significant complications after the implantation have been recorded. We suggest the current model as an additional appropriate tool for the investigation of spinal anesthesia. PMID- 2221415 TI - Is the antiemetic effect of the emulsion formulation of propofol due to the lipid emulsion? AB - The hypothesis that the lipid emulsion of the emulsion formulation of propofol is responsible for the low frequency of nausea, retching, and vomiting after propofol anesthesia was tested. A randomized, prospective, and comparative study was performed to evaluate the antiemetic effect of 10% lipid solution in 60 women, ASA physical status I and II, scheduled for ambulatory laparoscopic procedures. Two groups of patients were studied. Induction of anesthesia (thiopental) and maintenance of anesthesia (enflurane, nitrous oxide) were similar in both groups. At induction the study group received 10% Intralipid (3 mL/min for 20 min). The control group received 5% dextrose in lactated Ringer's solution at the same rate. Other drugs administered during or after anesthesia were similar among the groups. The groups were similar with respect to duration of anesthesia, characteristics of early and intermediate recovery, as well as pain scores in the postanesthesia care unit. There were no differences in the amount of antiemetic medications administered or postoperative nausea, retching, or vomiting when the patients were evaluated objectively by a blinded observer or subjectively by patient self-evaluation. It is concluded that 10% Intralipid, the lipid in the emulsion formulation of propofol, does not possess significant antiemetic effects. PMID- 2221416 TI - A comparison of conductivity-based hematocrit determinations with conventional laboratory methods in autologous blood transfusions. AB - An investigation was made of the accuracy of a portable hematocrit measurement device (Stat-Crit) on the infusate of an autologous blood transfusion system. Baseline hematocrit values were determined by three methods on in vivo blood samples of surgical patients immediately after the start of surgery, and again on the first product of the autologous blood retrieval system. At baseline, there were no significant differences in the values determined by the Stat-Crit (33.4% +/- 6.2%, mean +/- SD) and those determined by the microcentrifuge technique (33.8% +/- 4.7%) or by the Coulter method (33.5% +/- 4.5%) (P = 0.9). In contrast, hematocrit values determined on infusate samples by the Stat-Crit (36.6% +/- 4.8%) were significantly lower than those determined by the microcentrifuge technique (51.2% +/- 5.9%) or by the Coulter method (51.6% +/- 5.8%) (P = 0.0001). This study confirms close agreement of hematocrit values derived by the conductivity of whole blood in normal samples with those determined by conventional laboratory techniques, but indicates that this method will report falsely low readings in situations where plasma has been replaced by crystalloid, as in patients who have received large transfusions of processed autologous blood. PMID- 2221417 TI - Acute progesterone treatment has no effect on bupivacaine-induced conduction blockade in the isolated rabbit vagus nerve. AB - Pregnancy decreases anesthetic requirements during regional anesthesia. Using an in vitro animal model, this study attempts to elucidate the mechanism of hormonal effects on nerve conduction in desheathed rabbit vagus nerve. The acute effects of progesterone administration on neural blockade induced by bupivacaine were investigated in terms of changes in compound action potentials of A, B, and C fibers. No change in baseline compound action potential was found after 30 min of perfusion of the nerve with progesterone. Exposure of the nerve to progesterone before exposure to bupivacaine did not significantly increase the degree of conduction blockade produced by bupivacaine, and a radioactive assay demonstrated that progesterone was taken up acutely by neural tissue over a 45-min measurement period. These results indicate that although progesterone was taken up in significant amounts by neural tissue, an acute exposure does not increase the sensitivity of the nerves to bupivacaine. Hence, the increased sensitivity of nerves to local anesthetics seen with pregnancy or with chronic progesterone treatment requires some period of time to occur. The mechanism is therefore unlikely to be a direct effect of progesterone on the cell membrane but may involve hormonal effects on protein synthesis. PMID- 2221418 TI - Baseline activated coagulation time should be measured after surgical incision. AB - The activated coagulation time (ACT) is widely used to guide heparin and protamine dosing during cardiac surgery. A common protocol involves establishing a baseline ACT before administering heparin, then using this ACT as a target value for assessing the adequacy of heparin neutralization after cardiopulmonary bypass. Results vary in previous comparisons of baseline ACT to postprotamine ACT, with some showing postprotamine ACT significantly below baseline values. The present study examined ACTs at three possible baseline intervals in 68 patients at two institutions: (a) before anesthetic induction; (b) after anesthetic induction; and (c) after sternotomy. Baseline ACT decreased significantly with anesthesia and surgery. The poststernotomy baseline ACT best matched the postprotamine ACT. It appears likely that surgery induces a thromboplastic response that decreases ACT. Establishing baseline ACT before anesthetic induction would predispose to false diagnoses of adequate protamine neutralization after cardiopulmonary bypass, because ACT is relatively insensitive to low concentrations of unneutralized heparin. Baseline ACTs should therefore be measured after surgical incision. PMID- 2221419 TI - Treatment of refractory seizures in massive isoniazid overdose. PMID- 2221420 TI - Anesthetic management of cerebral aneurysm resection in a patient with idiopathic hypertrophic subaortic stenosis. PMID- 2221421 TI - Hearing loss after spinal anesthesia. PMID- 2221422 TI - Bupivacaine-induced cardiac arrest. PMID- 2221423 TI - Missed diagnosis of cuff herniation in a modern nasal endotracheal tube. PMID- 2221424 TI - Mixed venous oximetry may detect critical oxygen delivery. PMID- 2221425 TI - A simple method for reducing backup of blood into intravenous lines caused by inflation of a blood pressure cuff. PMID- 2221426 TI - ASA Award: John D. Michenfelder. PMID- 2221427 TI - Cardiorespiratory interactions in patients with an artificial heart. AB - A retrospective analysis of the influence of respiration was carried out in three patients with artificial hearts. During spontaneous ventilation, large swings in intrathoracic pressure can produce a pattern reminiscent of pulsus paradoxus in the systemic arterial pressure. A decrease in intrathoracic pressure decreased biventricular filling and enhanced biventricular emptying. An increase in intrathoracic pressure increased biventricular filling, but acting as an increased afterload, impeded biventricular emptying. The influence of respiration on the artificial heart can be considered the result of the artificial ventricles' functioning effectively as extrathoracic pumps, such that changes in intrathoracic pressure produce gradients for biventricular filling and ejection relative to atmospheric pressure (which serves as the reference pressure for the artificial ventricles). Respiratory-induced variation in ventricular performance is clearly present with the artificial heart, but the mechanisms producing these changes appear to be markedly different from normal conditions, in which the ventricles are functionally within the thorax and have a compliant common septum allowing ventricular interaction. PMID- 2221428 TI - The air test as a clinically useful indicator of intravenously placed epidural catheters. AB - The authors performed a clinical trial in 313 patients in labor to determine the safety and efficacy of an air test for unintentional intravenous placement of epidural catheters. Following routine aspiration for blood and cerebrospinal fluid, 1 ml of air was injected through each epidural catheter while heart tones were continually monitored with a Doppler ultrasound probe placed over the maternal precordium. In 281 patients, Doppler heart tones did not change following air injection (negative air test). All but eight of these patients developed an adequate level of analgesia following anesthetic administration, and no patients with negative air tests developed signs or symptoms of local anesthetic toxicity (false-negative rate, 0%; 95% confidence limits, 0.0-1.1%). Doppler heart tone changes followed air injection in 22 cases (positive air test). In 16 of these, intravenous catheter position was subsequently shown by aspiration of blood from the catheter or by the use of test doses consisting of local anesthetics with or without epinephrine. In six cases, adequate levels of analgesia developed despite a positive air test (false-positive rate, 2%; 95% confidence limit, 0.7-4.3%). None of the 303 patients receiving the air test developed any complications attributable to the injection of air (95% confidence limits, 0.0-1.0%). The authors conclude that air, with precordial Doppler detection, is a safe and effective test for identifying intravenously located epidural catheters. PMID- 2221429 TI - Quantitation of the interaction between atracurium and succinylcholine using closed-loop feedback control of infusion of atracurium. AB - The authors used closed-loop feedback control of infusion of atracurium to study the effect of prior administration of succinylcholine on neuromuscular blockade induced by atracurium in patients undergoing otolaryngologic surgery. Anesthesia was maintained with nitrous oxide in oxygen, flunitrazepam, and fentanyl. Of 14 patients given atracurium, seven were given prior administration of succinylcholine and seven were not. Interaction between the two drugs was quantified by determining the asymptotic steady-state rate of infusion necessary to produce a constant 90% neuromuscular blockade. This was accomplished by applying nonlinear curve-fitting to data on the cumulative dose requirement during anesthesia. The neuromuscular blocking effect of atracurium was found to be greater after prior administration of succinylcholine. The asymptotic steady state rate of infusion (+/- SD) for atracurium was 0.27 +/- 0.06 mg.kg-1.h-1 for patients given succinylcholine and 0.38 +/- 0.10 mg.kg-1.h-1 for those not given succinylcholine. The clinical implication of this study is that the clinician should be aware of the fact that an induction dose of 1 mg/kg of succinylcholine does reduce atracurium requirement for 90% neuromuscular blockade by approximately 30%. PMID- 2221430 TI - Relationship between anesthetic procedure and contact of anesthesia personnel with patient body fluids. AB - We recorded the frequency with which anesthesia personnel came in contact with patient body fluids in order to provide an empirical basis for the recommendation of relevant precautions. Anesthesia personnel completed a questionnaire when performing a range of standardized procedures. The rate of contact with blood was as follows: catheterization of peripheral vein, 18%; insertion of central venous catheter, 87%; arterial puncture, 38%; lumbar puncture, 23%; catheterization of the extradural space, 34%; tracheal intubation, 4%; tracheal extubation, 9%; suction of oral cavity, pharynx, or trachea, 13%; intramuscular injection of drug, 8%; and establishment or discontinuation of drip for blood transfusion, 43%. By using protective gloves, 98% of contacts with patient blood would have been prevented. Blood contact was more frequent in the emergency ward than in the operating room (P less than 0.05). Health care workers were not able to predict when a specific procedure would imply that contact with patient blood would occur. We recommend that specific precautions be adopted for the various procedures and discuss precautions that could have prevented contact with body fluid. PMID- 2221431 TI - Anterior fontanel pressure and visual evoked potentials in neonates and infants undergoing profound hypothermic circulatory arrest. AB - To determine the effects of cardiopulmonary bypass with profound hypothermic circulatory arrest (PHCA) on anterior fontanel pressure (AFP) and visual evoked potentials (VEPs), 21 neonates and infants undergoing cardiopulmonary bypass (CPB) with PHCA for surgical correction of congenital heart defects were studied. Mean (+/- SD) minimum nasopharyngeal, esophageal, and rectal temperatures of 16.4 +/- 2.2, 11.2 +/- 2.7, and 17.7 +/- 1.9 degrees C, respectively, were achieved for a mean duration of PHCA of 51.6 +/- 18.7 min. AFP increased significantly above pre-CPB values for the first 21.7 +/- 8.1 min of rewarming. The duration of this increase in AFP was related logarithmically and directly to the product of the nasopharyngeal temperature (NPT) at the end of PHCA and the duration of PHCA (r2 = 0.82, P less than 0.0001). Nineteen of these patients had simultaneous monitoring of VEPs. The latency of both the N70 and P100 components of the VEPs increased as temperature decreased. The cerebral perfusion pressure was linearly and inversely related to the AFP (r2 = 0.72, P less than 0.01). The VEPs disappeared as a nasopharyngeal temperature (NPT) of 18.9 +/- 2.8 degrees C and reappeared after 21.9 +/- 8.8 min post-PHCA at an NPT of 32.8 +/- 1.4 degrees C. There was no significant difference between duration of increased AFP (20.9 +/- 8.1 min) and the duration of absence of VEPs during the post-PHCA period. The duration of increased AFP correlated linearly and directly with the duration of absence of VEPs (r2 = 0.84, P less than 0.005). These data demonstrate that transient neurophysiologic dysfunction occurs after PHCA. This dysfunction is related to the duration of elevation of the AFP and cannot be explained solely by a temperature effect. PMID- 2221432 TI - Intraoperative 133Xe cerebral blood flow measurements by intravenous versus intracarotid methods. AB - To document the comparability of cerebral blood flow (CBF) values determined by quantification of 133Xe washout after either intravenous or intracarotid administration, 12 patients undergoing elective carotid endarterectomy anesthetized with N2O/O2 and either isoflurane or halothane were studied. Scintillation counters were placed over the middle cerebral artery territory ipsilateral to the operated carotid artery. CBF was measured by the intravenous method during dissection of the carotid sheath and was calculated as the initial slope index from head washout curves collected for 11 min after injection of 10 20 mCi 133Xe in saline into a large vein. Immediately prior to carotid occlusion, CBF was determined by direct injection of 1 mCi 133Xe in saline into either the internal carotid artery or the common carotid artery with the external carotid artery occluded. For the intracarotid injections, the initial slope was calculated from the 1st min of washout. Data were analyzed by linear regression and analysis of variance. Values are expressed as mean +/- SD. The mean CBF for intravenous and intracarotid methods were both 29 +/- 10 ml.100 g-1.min-1. The correlation between CBF measured by intravenous and intracarotid methods was excellent and was described by the line y = x + 0.6, r = 0.92. We conclude that in the flow range studied, the intravenous technique may be applied to measure CBF in physiologically stable situations in which direct intracarotid injection is not feasible. PMID- 2221433 TI - The "natural history" of segmental wall motion abnormalities in patients undergoing noncardiac surgery. S.P.I. Research Group. AB - Intraoperative segmental wall motion abnormalities (SWMA) detected by transesophageal echocardiography (TEE) are sensitive, but not always specific, markers of myocardial ischemia. To determine their incidence, characteristics, and relation to postoperative cardiac morbidity, we continuously recorded the left ventricular short-axis view and 12-lead ECG in 156 high-risk patients undergoing non-cardiac surgery. Monitoring was clinically blinded. Wall motion was scored at predefined clinical, hemodynamic, and ECG events and at periodic intervals (26 +/- 11 samples per patient). We detected 44 episodes of new or worsened SWMA in 32 patients (20%). The severity of most episodes was limited to severe hypokinesis (24/44, 55%) followed by akinesis (16/44, 36%) and dyskinesis (4/44, 9%). The remaining 124 patients had normal wall motion or only mild hypokinesis (56/156, 36%) or chronic SWMA (68/156, 44%). The incidence of new SWMA did not differ for patients with known coronary artery disease (CAD) and those with cardiac risk factors only (22% vs. 19%, P = not significant), although CAD patients had a significantly greater incidence of chronic SWMA (62% vs. 41%, P = 0.02). The incidence of new or worsened SWMA was significantly greater during aortic vascular surgery (38% vs. 17%, P = 0.05). Approximately 40% of all new TEE changes occurred in the absence of either an apparent clinical event or a significant change in systolic blood pressure or heart rate. Ten patients had new or worsened SWMA persisting until the end of surgery, 8 with new akinesis, only 1 developing myocardial infarction. The distribution of new or worsened SWMA and significant intraoperative ST-T changes (n = 19) in this cohort was discordant: temporal overlap between modalities was present in only 5 patients. Major cardiac complications occurred in 5 patients (3.2%), all of whom underwent peripheral vascularization. All patients with cardiac complications and new or worsened SWMA also had intraoperative or early postoperative ST-T changes. We conclude that: 1) continuous TEE recording with offline analysis in this high-risk group of patients revealed a relatively low incidence of new or worsened SWMA (20%), most episodes of which were characterized by severe hypokinesis (55%); 2) episodes were more common in patients undergoing aortic vascular surgery; 3) approximately 40% of episodes were unaccompanied by clinical events or significant hemodynamic changes; 4) episodes were poorly correlated with postoperative cardiac complications; and 5) the discordant relation between TEE and ECG changes observed here necessitates careful monitoring of the ECG when TEE is used clinically. PMID- 2221434 TI - Thermoregulatory vasoconstriction decreases cutaneous heat loss. AB - To determine the extent to which thermoregulatory vasoconstriction decreases heat loss to the environment, we measured regional heat flux, average skin temperature, and tympanic membrane temperature before and after thermoregulatory vasoconstriction in five minimally clothed volunteers maintained in a 30.8 +/- 0.1 degrees C environment. Thermoregulatory vasoconstriction was induced by central venous infusion of cooled fluid. Peripheral cutaneous blood flow was evaluated with venous-occlusion volume plethysmography and skin-surface temperature gradients. Laser Doppler flowmetry was used to measure vasoconstriction in centrally located skin. This model mimics the common clinical situation in which patients in a warm environment are centrally cooled by administration of cold intravenous fluids or by lavage of internal cavities with cold fluids. Tympanic membrane temperature decreased 1.5 +/- 0.3 degrees C in the first 15 min after the cold fluid infusion was started and remained approximately 1 degrees C below control values during the rest of the study. Average skin surface temperature decreased slowly to approximately 0.7 degrees C below control. Flow in capillaries of centrally distributed skin, determined with laser Doppler flowmetry, decreased only approximately 40%. Total heat flux, and flux from the arms and legs decreased approximately 25% (15.5 +/- 0.3 W). Heat loss from the trunk and head decreased only 17%, whereas, loss from the hands and feet (10.5% of the body surface area) decreased approximately 50%. All measured values decreased significantly following vasoconstriction (P less than 0.01). Therefore, thermoregulatory vasoconstriction in a thermoneutral environment appears to decrease cutaneous loss of metabolic heat approximately 25%. PMID- 2221435 TI - Hormonal-metabolic stress responses in neonates undergoing cardiac surgery. AB - Hormonal and metabolic responses were measured in 15 neonates who underwent repair of complex congenital heart defects during a standardized anesthetic protocol. Four of the 15 neonates died postoperatively in the intensive care unit. Analysis of arterial plasma samples obtained before, during, and 24 h after surgery showed that plasma epinephrine, norepinephrine, cortisol, glucagon, and beta endorphin increased in all patients (P less than 0.05). Insulin levels increased only at the end of surgery but remained elevated for 24 h postoperatively (P less than 0.02). Intraoperative metabolic changes were characterized by hyperglycemia and lactic acidemia that persisted postoperatively. This pattern of neonatal stress responses is distinct from and more extreme than that seen in adult cardiac surgical patients. The four neonates who died postoperatively tended to have higher stress responses intra- and postoperatively despite having been indistinguishable from survivors by the usual clinical and hemodynamic criteria. These preliminary results suggest that neonatal hormonal and metabolic responses to cardiac surgical operations in neonates are extreme and are associated with a high hospital mortality rate. PMID- 2221436 TI - hemofiltration reverses left ventricular dysfunction during sepsis in dogs. AB - Depressed left ventricular (LV) contractility in sepsis has been ascribed to the presence of circulating cardiodepressant substance (filterable cardiodepressant factor in sepsis [FCS]); however, this finding is controversial. The authors hypothesized that if a decrease in LV contractility indeed occurred due to a circulating depressant substance, then removal of this substance by hemofiltration would reverse by dysfunction. In this study, LV mechanics were examined before and after hemofiltration in anesthetized dogs during continuous intravenous infusion of live Escherichia coli. Left ventricular anterior posterior and apex-base dimensions were measured by subendocardial ultrasonic crystal transducers implanted 4 weeks before the experiments. Left ventricular contractility was determined from the end-systolic pressure-dimension relationship. The slope of this relationship (Emax) is an index of contractility. After 4 h of sepsis, Emax was reduced by one half. Hemofiltration resulted in a return of Emax to control values. The FCS activity in the plasma was also assessed by the percent reduction in isometric contraction of electrically stimulated, isolated right ventricular trabeculae obtained from nonseptic dogs. The FCS activity reached a peak 4 h after sepsis and was reduced after 2 h of hemofiltration. The results show that during experimental sepsis, a circulating substance of less than 30,000 d produces a decrease in LV contractility and that this LV dysfunction may be improved by hemofiltration. PMID- 2221437 TI - Nitrous oxide does not alter infarct volume in rats undergoing reversible middle cerebral artery occlusion. AB - This experiment was designed to determine if nitrous oxide alters neurologic and pathologic outcome from temporary focal cerebral ischemia in spontaneously hypertensive rats deeply anesthetized with a barbiturate. Two groups of rats were given intravenous methohexital such that a stable EEG pattern of burst suppression was achieved. In one group of rats (n = 11), the lungs were mechanically ventilated with 70% N2O/30% O2, and in the other group (n = 10), ventilation was done with 70% nitrogen/30% O2. The middle cerebral artery was then occluded for 2 h, during which time mean arterial pressure, blood gases, hematocrit, plasma glucose, and head temperature were held constant between groups. The total doses of methohexital administered were similar in both groups as were the plasma methohexital concentrations immediately prior to onset of ischemia. After reperfusion of the middle cerebral artery, the animals were allowed to awaken. Neurologic evaluations were performed prior to ischemia and at 24 and 96 h postischemia. Cerebral infarct volume was measured at 96 h postischemia using triphenyl tetrazolium chloride staining and computer imaging techniques. There were no neurologic differences between the N2O and nitrogen groups at any experimental interval although both groups exhibited deficits at both 24 and 96 h postischemia relative to preischemic values. The two groups also had nearly identical cerebral infarct volumes (N2O = 231 +/- 97 mm3; nitrogen = 226 +/- 75 mm3; mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221438 TI - Endogenous vasopressin supports blood pressure and prevents severe hypotension during epidural anesthesia in conscious dogs. AB - To evaluate whether, and to what extent, release of endogenous vasopressin supports blood pressure when efferent sympathetic drive is blocked by epidural anesthesia, the authors studied the effects of high epidural anesthesia alone and when vasopressin was prevented from acting at its vascular (V1)-receptor in six awake, trained, unsedated dogs. On different days, the same dose of 0.5% bupivacaine (8-13 ml) was injected epidurally in a randomized fashion either in the presence or absence of (V1)-vasopressin receptor blockade, and the effects were evaluated on cardiovascular (arterial blood pressure, heart rate) and respiratory (blood gases, oxygen consumption) variables, and on plasma concentrations of vasopressin and renin. Results were also contrasted to those obtained after epidural injection of saline alone (placebo) in the same dogs. When endogenous vasopressin was prevented from acting by intravenous pretreatment with a specific V1-receptor antagonist (beta-mercapto-beta, beta-cyclopenta methylene-propionyl-O-Me-Tyr-Arg-Vasopressin), epidural anesthesia resulted in a rapid and sustained 35% decrease in mean arterial blood pressure from 92 mmHg +/- 5 SE to 60 mmHg +/- 4. In contrast, only a 14% decrease in mean blood pressure from 92 mmHg +/- 5 to 79 mm Hg +/- 6 was noted after epidural anesthesia alone. This difference between groups was statistically significant (P = 0.0001). The V1 receptor blockade alone had no detectable effect. Vasopressin plasma concentrations significantly increased from 3.4 +/- 0.3 pg.ml-1 to 16.2 +/- 3.2 pg.ml-1 after epidural anesthesia but did not change after epidural saline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221439 TI - Resistance to d-tubocurarine in lower motor neuron injury is related to increased acetylcholine receptors at the neuromuscular junction. AB - The hypothesis that lower motor neuron injury, with its associated proliferation of acetylcholine receptors (AChR), induces resistance to the neuromuscular effects of d-tubocurarine (dTC) was tested in the rat. The left gastrocnemius was denervated by a 75-80% lesion of the sciatic nerve. The effective dose for 95% twitch depression (ED95) was studied in the denervated gastrocnemius and compared to the contralateral undenervated and sham-injured (control) gastrocnemius muscles approximately 2 weeks after injury. The AChR number was quantitated by the specific ligand 125I-alpha-bungarotoxin (125I-alpha-BT). Plasma dTC concentrations, measured by high-performance liquid chromatography (HPLC), were correlated to twitch tension during spontaneous recovery from neuromuscular blockade in the denervated animal. The ED95 (mean +/- SE) of dTC for the denervated leg was significantly (P less than 0.05) higher (0.26 +/- 0.06 mg.kg 1) than contralateral (0.16 +/- 0.03) and sham-operated left (0.13 +/- 0.03) legs. The twitch tension recovered to 50% of control twitch height at significantly (P less than 0.05) higher plasma dTC concentrations in the denervated (0.78 micrograms.ml-1) compared to contralateral (0.24 micrograms.ml 1) limb. The AChR number was significantly increased in the denervated limb (1041 +/- 96 fmol.mg protein-1) compared to contralateral right (109 +/- 4) and control left limb (113 +/- 11). There was a significant (P less than 0.05) positive correlation (R2 = 0.73) between ED95 and AChR number; that is, 73% of the variability in ED95 could be explained by changes in AChR. This study, therefore, confirms the hypothesis that proliferation of AChR after nerve denervation results in resistance to the neuromuscular effects of dTC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221440 TI - The minimum alveolar concentration (MAC) and hemodynamic effects of halothane, isoflurane, and sevoflurane in newborn swine. AB - To determine the minimum alveolar concentration (MAC) and hemodynamic responses to halothane, isoflurane, and sevoflurane in newborn swine, 36 fasting swine 4-10 days of age were anesthetized with one of the three volatile anesthetics in 100% oxygen. MAC was determined for each swine. Carotid artery and internal jugular catheters were inserted and each swine was allowed to recover for 48 h. After recovery, heart rate (HR), systemic systolic arterial pressure (SAP), and cardiac index (CI) were measured awake and then at 0.5, 1.0, and 1.5 MAC of the designated anesthetic in random sequence. The (mean +/- SD) MAC for halothane was 0.90 +/- 0.12%; the MAC for isoflurane was 1.48 +/- 0.21%; and the MAC for sevoflurane was 2.12 +/- 0.39%. Awake (mean +/- SD) measurements of HR, SAP, and CI did not differ significantly among the three groups. Compared to the awake HR, the mean HR decreased 35% at 1.5 MAC halothane (P less than 0.001), 19% at 1.5 MAC isoflurane (P less than 0.005), and 31% at 1.5 MAC sevoflurane (P less than 0.005). Compared to awake SAP, mean SAP measurements decreased 46% at 1.5 MAC halothane (P less than 0.001), 43% at 1.5 MAC isoflurane (P less than 0.001), and 36% at 1.5 MAC sevoflurane (P less than 0.005). Mean SAP at 1.0 and 1.5 MAC halothane and isoflurane were significantly less than those measured at equipotent concentrations of sevoflurane (P less than 0.005). Compared to awake CI, mean CI measurements decreased 53% at 1.5 MAC halothane (P less than 0.001) and 43% at 1.5 MAC isoflurane (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221441 TI - Halothane decreases the release of neuropeptide Y and 3,4-dihydroxyphenylglycol from superfused segments of dog pulmonary artery. AB - Neuropeptide Y (NPY), norepinephrine (NE), and 3,4-dihydroxyphenylglycol (DOPEG), the metabolite of NE that arises intraneuronally, were measured in superfusates before, during, and after nerve stimulation and in extracts of dog pulmonary artery after superfusion and electrical stimulation (ES) at 12, 6, and 1 Hz. NE and DOPEG were quantified by high-pressure liquid chromatography with electrochemical detection; peptides were quantified by radioimmunoassay. The rate of overflow of NPY, NE, and DOPEG into superfusate was measured over time. The overflow of DOPEG into superfusate during basal conditions was 3.0 times that of NE. Efflux of DOPEG and NPY increased during ES; peak effluxes were not reached, however, until after cessation of stimulation. NE efflux peaked during ES. Effluxes of NE, NPY, and DOPEG were frequency-dependent at 12 and 6 Hz; at 1 Hz efflux of only NE was greater than basal. Halothane decreased significantly the rates of NPY and DOPEG efflux during and after 12 Hz ES; DOPEG efflux evoked by 6 Hz stimulation was also decreased by halothane. The percentage of the total tissue content of NPY that overflowed was decreased by halothane. Halothane did not affect the molar ratios of NE:DOPEG or NE:NPY during basal conditions or ES. These studies provide evidence that halothane slows efflux of NPY that is released along with NE from dog pulmonary artery during high frequencies of stimulation. Halothane also reduces the metabolism of NE to DOPEG. PMID- 2221442 TI - Volatile anesthetic effects on left ventricular relaxation in swine. AB - The effects of halothane (0.5, 1.0, and 1.5%; n = 10), enflurane (1.0, 2.0, and 3.0%; n = 8), and isoflurane (0.75, 1.5, and 2.25%; n = 8) on isovolumic relaxation were studied in open-chest swine. The time constant for isovolumic left ventricular pressure decline, T, was determined at each anesthetic concentration at the intrinsic heart rate and during atrial pacing to 150 beats per min. The effect of increased left ventricular afterload on T was investigated by partial occlusion of the thoracic aorta to raise the left ventricular systolic pressure to baseline in the presence of volatile anesthetics, and 20% above baseline in the absence of volatile anesthetics. Heart rate and left ventricular systolic pressure decreased substantially with all three anesthetics, whereas left ventricular end-diastolic pressure increased (by 3-4 mmHg). Relaxation time constants increased with all three anesthetics at the intrinsic heart rate; when the heart rate was controlled by pacing, T increased in the halothane and enflurane, but not in the isoflurane, experiments. T was significantly prolonged (by 30-100%) by partial aortic occlusion in the presence of anesthetic, but not in the control measurements. T did not change significantly in the isoflurane experiments when atrial pacing was employed with partial aortic occlusion. The volatile anesthetics, particularly halothane, seem to impair the relaxation process of the left ventricle; further investigation of the mechanisms of this interference, such as anesthetic effects on intracellular calcium movement and total left ventricular load, is warranted. PMID- 2221443 TI - Dwarfs: pathophysiology and anesthetic implications. PMID- 2221444 TI - Continued demonstration of qualifications for board-certified anesthesiologists. PMID- 2221445 TI - Guide wire as a cause of complete heart block in patients with preexisting left bundle branch block. PMID- 2221446 TI - Airway compromise from prevertebral soft tissue swelling during placement of halo traction for cervical spine injury. PMID- 2221447 TI - Mallory-Weiss tear complicating intraoperative transesophageal echocardiography in a patient undergoing aortic valve replacement. PMID- 2221448 TI - An unusual presentation of intercostal neuralgia. PMID- 2221449 TI - Acute upper airway obstruction due to arterial puncture during percutaneous central venous cannulation of the subclavian vein. PMID- 2221451 TI - Epidural opioids as a cause of vertical nystagmus. PMID- 2221450 TI - Perioperative diagnosis of subclavian artery stenosis: a contraindication for internal mammary artery-coronary artery bypass graft. PMID- 2221452 TI - Emergency transtracheal jet ventilation system. PMID- 2221453 TI - Transtracheal jet oxygenator from capnographic monitoring components. PMID- 2221454 TI - Propofol during cesarean section. PMID- 2221455 TI - Patient-controlled epidural anesthesia during labor may be hazardous. PMID- 2221457 TI - Effects of epidural saline and epidural fentanyl. PMID- 2221456 TI - Inappropriate use of the t-test. PMID- 2221458 TI - Early reports of pulmonary aspiration during general anesthesia. PMID- 2221459 TI - Linear regression is a poor descriptor of accuracy. PMID- 2221460 TI - Timing of data acquisition determines image quality in femoropopliteal phase sensitive MR angiography. AB - To study the effects of timing of data acquisition on quality of femoropopliteal magnetic resonance (MR) angiograms, the authors studied 16 healthy men, mean age 34.3 +/- 6 years, by color Doppler imaging and by phase-sensitive (PS) MR angiography. PS MR imaging was performed at 1.5T using a flow adjustable gradient (FLAG) pulse sequence. The images were graded in a blinded fashion by two independent observers. Of 16 MR angiograms consisting of 141 angiographic images (AI), 45 (31.9%) were diagnostic. At least 1 diagnostic AI was obtained in each subject, and 38 (84.4%) of the diagnostic images were acquired within the first 120 milli-seconds (ms) of the systolic flow pulse. The highest yield of diagnostic images (90.9%) was obtained in the interval of thirty to sixty ms before the peak flow velocity. In healthy man diagnostic PS MR angiography requires triggering to the femoropopliteal systolic flow pulse. The highest yield of diagnostic images is acquired during the flow pulse acceleration. PMID- 2221461 TI - Optimizing heparin utilization in angiographic flush solutions. AB - Various concentrations of heparin in angiographic flush solutions are employed during angiography. In an effort to determine whether differences in outcome are seen when either high or low concentrations of heparin in angiographic flush solutions are utilized, two groups of patients were evaluated. There was no difference in outcome and a small systemic effect from heparin was seen in both groups. Use of a low concentration of heparin is suggested for routine angiography. PMID- 2221462 TI - Hindbrain ischemia produced by bilateral vertebral artery occlusion and moderate hypotension in spontaneously hypertensive rats. AB - Hindbrain ischemia was induced by bilateral vertebral artery occlusion and moderate hypotension in spontaneously hypertensive rats (SHRs). Mean arterial blood pressure was lowered to 80 mmHg in SHRs and to 50 mmHg in Wistar-Kyoto rats (WKYs) by a controlled hemorrhage, and then the vertebral artery was bilaterally occluded through alar foramina of the first cervical vertebra. Following vertebral occlusion, blood flow of the cerebellum was significantly decreased to 9.4 +/- 2.0 mL/100g/min (+/- SEM) while flow of the cerebrum remained at 32.1 +/- 5.4 in SHRs. In contrast, cerebellar blood flow in WKYs was preserved at 24.2 +/- 2.9 mL/100g/min. Brain lactate, pyruvate, and adenosine triphosphate (ATP) were determined in SHRs after sixty minutes of hypotension with or without vertebral occlusion. Although infratentorial metabolites were actually unaltered in rats with hypotension alone, infratentorial lactate and lactate/pyruvate ratio significantly increased to 14.38 +/- 3.61 mmol/kg and 67.7 +/- 12.1, respectively, with a concomitant decrease in ATP in SHRs with hypotension and vertebral occlusion. Bilateral vertebral artery occlusion, together with moderate hypotension, was shown to produce a marked reduction of cerebellar blood flow and to induce ischemic metabolic changes in the infratentorial brain in SHRs. PMID- 2221463 TI - Clinical evaluation of a novel ambulatory automatic blood pressure monitoring system. AB - Reliability and reproducibility of a new automatic ambulatory blood pressure recorder were tested on 31 subjects (18 normotensives and 13 hypertensives). Of 3688 recordings, 1424 measurements were cross-checked with a sphygmomanometer in standing or sitting position at the beginning and at the end of a twenty-four hour monitoring period. In the normotensive subjects cross-checkings were performed also during a treadmill exercise stress test. Analysis of variance did not indicate statistical differences between the two types of measurement (p greater than 0.09 for systolic and p greater than 0.62 for diastolic), and a significant linear correlation was found at rest (r = 0.99, p less than 0.001 for systolic and r = 0.98, p less than 0.001 for diastolic pressure). During the effort test the device was unable to correctly measure blood pressure values after the first step. During the twenty-four hour monitoring period only 1.1% of the preprogrammed measurements were lost for each subject. The recorder seems to be a suitable and reliable tool for automatic blood pressure monitoring. PMID- 2221464 TI - Effect of high-dose furosemide in refractory congestive heart failure. AB - High-dose firosemide is considered effective in primary renal sodium retention but is not generally recommended in congestive heart failure. In order to evaluate efficacy and safety of high-dose furosemide (greater than 500 mg/day), the authors studied 20 patients (pts) resistant to therapy (including furosemide less than 500 mg/day) selected from 161 pts admitted for chronic heart failure. All refractory pts (15 men and 5 women, mean age sixty +/- 12 years) were in NYHA class IV and showed hyponatremia (130 +/- 5 mEq/L) and impaired renal function (BUN 31 +/- 14 mg/dL, serum creatinine 1.3 +/- 0.3 mg/dL and BUN/creatinine ratio 23 +/- 7). In addition to digitalis, dopamine, angiotensin-converting enzyme inhibitors, or vasodilators, IV high-dose furosemide (775 +/- 419 mg/day, 500 2000) was given for ten +/- five days under daily clinical and laboratory monitoring. Three pts died of low-output syndrome while 16 pts were upgraded to NYHA class III and 1 pt to class II; a mean weight reduction of 7.3 +/- 2.9 kg in ten + five days (0.80 +/- 0.4 kg/day) and a mean diuresis increase of 88 +/- 57% occurred. The maximal dose of furosemide did not correlate with serum creatinine but did correlate with BUN/creatinine ratio (r = 0.78, p less than .001). Pts were discharged on with chronic heart failure, and 43% in the subgroup in NYHA class IV with hyponatremia. High dose furosemide was effective for rapid removal of excess water and salt in "furosemide-resistant" congestive heart failure. The relationship between renal impairment and maximal furosemide doses seems to confirm the role of renal pharmacokinetics in the appearance of furosemide resistance. PMID- 2221465 TI - Comparison of standard one-minute treadmill exercise and strandness test (absolute walking distance) in relation to site of lesion, walking distance, and diastolic blood flow velocity (Doppler curves). AB - In 215 outpatients suffering from occlusive arterial disease of the lower limbs the authors compared the decrease in the ratio of ankle systolic pressure to brachial systolic pressure according to whether the treadmill exercise was limited to one minute or extended until pain forced the patient to stop. After a one-minute walk the pressure index always decreased significantly, especially when walking was restricted. The decrease in the pressure index was generally greater when the exercise was continued until the absolute walking distance, and the recovery time was usually twice as long. The fall in the pressure index was significantly greater for patients with single and multiple iliac stenoses than for those with stenoses at lower levels. In patients having a diastolic blood flow velocity on Doppler curves at rest, not modified by walking, a maximum drop in peripheral pressure was recorded after walking for one minute. In this instance there was no intensification of the decrease in peripheral pressure, unlike in patients without a diastolic blood flow velocity at rest. This one minute test is not a maximal hemodynamic response, but it is sufficient for the appreciation of ischemia during exercise, according to the different parameters measured. PMID- 2221466 TI - Use of Doppler flow velocity waveform analysis in detection of initial diabetic microangiopathy. AB - Doppler flow velocity waveform analysis (FVWFA), recorded from the dorsalis pedis artery (DPA) and the radial artery (RA), was performed on 36 women in attempting to detect an initial diabetic microangiopathy (DM). The study comprised two groups of women affected by non-insulin-dependent diabetes mellitus, 6 patients (pts) of reproductive age (1), 12 pts in menopause (II), and two groups of age matched healthy controls (C) (III and IV). Clinical signs of initial DM were present in group I. All the examined pts were nonsmokers and normotensive and without cardiopathy, signs of diabetic macroangiopathy, collagen vascular disease and/or Raynaud's phenomenon, and renal failure. Four waveform dimensions capable of separating different degrees of peripheral obstructive arteriolar disease were determined on velocity tracing and the results used in a single best discriminant equation. The resultant discriminant score (DS), derived by FVWFA on DPA, showed a highly accurate rate of separating the young pts with DM from both C and the pts in menopause without DM. Furthermore, the resultant DS was statistically not different in groups II, III, and IV. In conclusion, FVWFA on DPA, in this experience, has proved to be an accurate and sensitive method in the detection of initial DM. PMID- 2221467 TI - Coronary artery dissection--a case report. AB - Coronary artery dissection, both spontaneous and catheter-induced, is associated with a significant morbidity and mortality. The authors present a case of a middle-aged woman with spontaneous right coronary artery dissection causing inferior wall myocardial infarction and left coronary artery dissection at the time of coronary arteriography. It is suggested that emergency aortocoronary bypass surgery be performed preceded by insertion of an intra-aortic balloon in acute evolving cases where coronary anatomy is favorable to limit infarction and avert loss of life. PMID- 2221468 TI - A forme fruste of Marfan's syndrome: case history. AB - A thirty nine year old woman presented with multiple aneurysms and dissections of the arterial system secondary to cystic medial necrosis is presented. After assessment of the family history a diagnosis of a forme fruste of Marfan's syndrome was made. Preoperative consideration of this rare diagnosis is important for treatment and surgical management. PMID- 2221469 TI - Underestimation of treatment effect in crossover trials. AB - In crossover trials each subject serves as his own control. For the study of cardiovascular diseases such as hypertension and angina pectoria, properly designed crossover studies are preferred to parallel studies. There is a considerable between-subject variability of symptoms in some of these conditions. Bias due to this is eliminated by the use of a crossover design. However, a problem is the so-called treatment-by-period interaction. The present study analyzes the potential influences of this on the outcome of the trial. Physical carryover effect, defined as a physical effect of the first treatment period carrying on into the second, tends to minimize differences between two consecutive treatment periods. So does the frustrating experience of an inactive agent in the first treatment period. Outside influences such as the change of the seasons may affect lengthy crossover trials in a similar way. The author concludes that the treatment effect in a crossover trial tends to be underestimated. The current concept that reports of clinical trials are generally biased toward an exaggeration of treatment effects does not seem to apply to crossover trials. PMID- 2221470 TI - Electrocardiographic abnormalities in cerebrovascular accidents. AB - The electrocardiographic abnormalities found in 100 patients with acute cerebrovascular disease and previously normal hearts are described. The abnormalities were more often seen in patients with intracerebral and subarachnoid hemorrhages. The most common changes were Q-Tc Prolongation and ST segment and T wave abnormalities. The mechanisms of these electrocardiographic abnormalities appear to be multiple. PMID- 2221472 TI - The effect of local temperature versus sympathetic tone on digital perfusion in Raynaud's phenomenon. AB - Matched groups of 7 to 8 patients with primary Raynaud's phenomenon, systemic sclerosis, and undifferentiated connective tissue disease and cold-tolerant normal control subjects were studied by simultaneous digital strain gauge plethysmography and laser Doppler capillary velocimetry during two controlled cycles of hand warming and cooling with and without addition of central cooling and during clinical maneuvers to evoke sympathetic tone. Transient vasoconstrictor responses of comparable degree could be evoked in all patient groups and in both the arterial and microvascular beds. While the addition of central cooling had little influence on arterial flow, patients with systemic sclerosis manifested a failure to maintain nutritive perfusion at finger temperatures associated with Raynaud's phenomenon. Linear regression and multivariate analysis suggested that finger temperature was the principal determinant of arterial flow in systemic sclerosis and that arterial flow was the principal determinant of microvascular perfusion. The inability of patients with systemic sclerosis to maintain nutritive flow in the face of either reflex or cold-induced proximal arterial constriction is consistent with their clinical propensity to ischemic tissue injury and separates these patients physiologically from other forms of Raynaud's phenomenon. PMID- 2221474 TI - Transient reversal of inverted U waves during Valsalva's test--a case report. PMID- 2221473 TI - Successful direct PTCA on LAD after first episode of acute myocardial infarction: does it improve cardiac function? AB - Patients who received direct percutaneous transluminal coronary angioplasty (PTCA) after acute mycardial infarction and maintained potency but with unimproved cardiac function were studied. In 15 patients, the first episode of acute myocardial infarction was caused by a left anterior descending branch lesion; 11 had an ejection fraction of 50% or more in the left ventriculogram in the follow-up period (improved group), and 4 patients had ejection fraction of less than 50% (unimproved group). There was so significant difference between the groups in the mean time between the onset of infarction and revascularization (improved group, 259.3 +/- 76.9 min; unimproved group, 168.0 +/- 101.6 min) or in the sigma Q. which was the sum of the Q wave depth of V2, V3, and V4 at the time of admission (improved group, 12.1 +/- 15.6 mm; unimproved group 29.8 +/- 13.4 mm). The maximum creatine kinase concentration was significantly higher in the unimproved group (improved group 2670 +/- 893 IU/L; unimproved group, 7243 +/- 1928 IU/L, p less than 0.05), and the time taken from the onset to reach its peak was significantly shorter in the unimproved group (improved group, 13.0 +/- 5.1 hr; unimproved group, 6.8 +/- 1.3 hr, p less than 0.05.) These results suggest the probability of sudden deterioration of myocardium, and factors other than microcirculatory thromboembolism should be considered as the cause of unimproved cardiac function after successful direct PTCA. PMID- 2221471 TI - Does the decrease in heart rate prevent a detrimental decrease of the end systolic volume during central hypovolemia in man? AB - Central hypovolemia occurring with epidural anesthesia was investigated by measurement of hemodynamic and endocrine variables in 10 patients. Responses fell into two categories. Four patients experienced a hypotensive bradycardic episode after seventeen +/- four minutes. In this group epidural anesthesia initially induced a tendency toward an increase in heart rate from 65 +/- 4 to 73 +/- 5 beats/min concomitantly with decreases in end-diastolic (172 +/- 22 to 138 +/- 16 mL), end-systolic (67 +/- 12 to 51 +/- 9 mL), and stroke (105 +/- 10 to 85 +/- 7 mL) volumes (radionuclide cardiography). A subsequent decrease in mean arterial pressure from 76 +/- 3 to 67 +/- 4 mmHg was associated with a decrease in venous return as reflected by the decrease in cardiac output from 6.1 +/- 0.4 to 4.7 +/- 0.7 L/min. In this situation when the venous return was critically reduced, the heart rate was 49 +/- 4 beats/min and no further reduction in end-diastolic and end-systolic volumes was observed. The observed endocrine changes were compatible with a response to central hypovolemia. In the other 6 patients the reaction to epidural anesthesia did not induce statistically significant changes in hemodynamic and endocrine variables. It is concluded (1) that the decrease in heart rate associated with central hypovolemia during epidural anesthesia seems to be elicited when the left ventricular end-systolic volume is decreased by about 25% and (2) that a further decrease in end-systolic volume during progressive central hypovolemia is avoided possibly as a direct consequence of the slowing of the heart. PMID- 2221475 TI - Laser angioplasty: a critical review based on 1849 clinical procedures. PMID- 2221476 TI - Arterial revascularization by laser angioplasty: first Italian experiences. AB - Eighty-seven laser angioplasty procedures were performed on 85 patients (73 men and 12 women). In the first phase (54 patients) a broad selection process included long occlusions (23.9 cm avg) and vessels with heavy calcification; in the second phase (31 patients) the authors treated vessels with shorter occlusions (10 cm avg) and less calcific. The primary success rate, based on number of procedures (73.5% overall) was 69% in the first phase but reached 81.3% in the second phase. There were 14 perforations (16%), 8 dissections (9.4%), and 4 peripheral emboli (4.7%). Six-month follow-up shows that the Winsor index maintained its initial improvement in 76.5% of all patients, or 62% in just the long occlusions. These data and a review of the cases suggest that no more of 10 20% of patients with claudication in lower extremities can be treated by laser angioplasty; the authors consider ideal candidates those patients who noncalcific lesions in the common iliac or superficial femoral arteries at the III medium level with obstructions shorter than 8 cm and good runoff. PMID- 2221477 TI - Effects of a 2.15-micron laser on human atherosclerotic xenografts in vivo. AB - The thulium-holmium-chromium:yttrium-aluminum-garnet (THC:YAG) laser has a tissue effect similar to that of the CO2 laser, with the advantage of transmissibility through flexible fibers. The authors used a human-rabbit xenograft model to evaluate the thrombotic and healing responses of atherosclerotic vessels subjected to laser energy. Occluded atherosclerotic human coronary artery segments were recanalized in vitro by use of the THC:YAG laser. Destruction of plaque by the laser was achieved with minimal collateral thermal damage. These vascular segments were then transplanted into the rabbit abdominal aorta. The authors observed that the luminal surface of the lased vessels was more thrombogenic than that of the nonlased control vessels. However, occlusion of the lased vessels did not occur. Repair of laser-treated tissue progressed until a mature, nonthrombogenic fibrin-platelet aggregate was adherent to the luminal wall. Overall, the lased vessels behaved in a fashion similar to the nonlased control vessels. On the basis of these results, the authors believe that the THC:YAG laser may have use in human angioplasty. PMID- 2221478 TI - Intraoperative coronary excimer laser angioplasty: preliminary clinical experience. AB - Diffuse coronary artery atherosclerosis is generally recognized as a deterrent to successful revascularization if it cannot be adequately treated. Mechanical endarterectomy can be useful, but it is not the optimal solution owing to the associated higher incidences of perioperative infarction and mortality. The use of laser energy as an endarterectomy tool appears promising. To investigate the application of excimer laser radiation to intraoperative coronary artery endarterectomy, 15 stenotic lesions in 13 patients were treated with excimer irradiation during coronary artery bypass grafting. Eleven (73%) of the lesions were enlarged by the excimer probe (6 of the successes were in calcified lesions). The 4 arteries not enlarged by the excimer laser all demonstrated calcified lesions. There were 3 perforations and 2 dissections, all but 1 in heavily calcified arteries. The results of this phase 1 safety and efficacy study indicate that excimer irradiation can recanalize most arteries, including total and subtotal occlusions and some calcified lesions. Further evaluation with better delivery systems is needed to determine whether the perforation rate can be reduced. PMID- 2221479 TI - Intraoperative coronary angioscopy: development of practical techniques. AB - Techniques and equipment for intraoperative coronary angioscopy were studied in the coronary arteries and cardiac veins of excised and in vivo animal hearts. These studies then allowed development of safe, practical techniques for human clinical use. In coronary artery bypass operations, multichannel angioscopes of 2.3 to 2.8 mm diameter gave the best results for examinations of the bypass vein and anastomosis, whereas smaller optical fibers of 1 mm diameter were required for inspection of the native coronary artery. Abnormalities were detected in 11 of 48 (23%) coronary bypass anastomoses, and significant discrepancy in the degree of coronary artery stenosis as compared with the preoperative angiogram was revealed in 2 patients. The authors concluded that a new design of ultrafine, multichannel angioscope would be more suitable to the different requirements for inspection of both the anastomosis and the recipient artery. PMID- 2221480 TI - Intravascular laser therapy of acute myocardial infarction. AB - The efficacy of a new method of treatment, endovascular blood irradiation with He Ne laser, developed by the authors, was studied in 295 patients with primary acute transmural myocardial infarction (MI). Twenty-four-hour Holter monitoring findings before and after laser irradiation suggested the possibility of preventing sudden death in the acute period of MI owing to the high anti arrhythmic efficacy of the method with respect to high-grade ventricular arrhythmias. Precodial ECG mapping and serial determination of blood enzyme activities (CPK and MB-CPK) showed that irradiation performed within the first hours of MI development contributed to effective limitation of the infarction area and restricted the spread of the area of myocardial ischemic damage. PMID- 2221481 TI - Blinding reviewers improves peer review. PMID- 2221482 TI - The hidden tonsils of Waldeyer's ring. AB - The visible and the hidden tonsils of Waldeyer's ring merit attention from specialists in allergy and clinical immunology not only because they are sites of antigen recognition and synthesis of antibody, including IgE, but also because they may produce a wide range of symptoms in the upper airway. Ordinarily, such symptoms may be differentiated from those of classic allergic rhinitis, but allergists commonly see patients with a variety of upper airway complaints that on investigation prove not to have an allergic basis. Use of flexible fiberoptic upper airway endoscopy, a simple office procedure that permits direct inspection of the recessed areas of the upper airway, will result in timely evaluation and treatment of pathology of these upper airway lymphatic structures, and identification of patients requiring referral to another specialist. PMID- 2221483 TI - Adverse reactions to heparin. AB - Heparin is a medication that has gained widespread use in clinical medicine as the therapy of choice for acute anticoagulation in the prevention and treatment of thromboembolic disease. Therapy with heparin is associated with many potential adverse side effects. Heparin-induced skin necrosis is an uncommon complication of heparin therapy that is now believed to be a thrombotic complication of heparin-induced thrombocytopenia. The pathogenesis of this disorder is unknown, but it is presumed to be immunologically mediated. The diagnosis is frequently one of exclusion. Significant morbidity and mortality may arise from failure to recognize this adverse reaction. PMID- 2221484 TI - Bakers' asthma: prevalence and evaluation of immunotherapy with a wheat flour extract. AB - One hundred thirty-nine bakers and pastry cooks were included in a prevalence study of IgE-mediated hypersensitivity to wheat flour demonstrated by skin tests, specific IgE to wheat flour (RAST), and inhalation challenge. From the sensitized workers, we selected 30 asthmatic patients. Twenty patients were treated with a standardized wheat flour extract, and ten with a placebo in a double-blind clinical trial. Before and after immunotherapy we performed tests in vivo (skin tests with wheat flour and methacholine tests), and in vitro (total IgE and specific IgE to wheat flour). We found substantial prevalence of wheat flour allergy (25.17% of workers), and a significant decrease (P less than .001) in hyperresponsiveness to methacholine, skin sensitivity (P = .002), and specific IgE (P less than .005) to wheat flour after 20 months of immunotherapy. There was also significant subjective improvement (P less than .001). The placebo group showed no changes in these variables. PMID- 2221485 TI - Exercise-induced biphasic responses and methacholine reactivity in asthma. AB - Biphasic (early and late) asthmatic responses to exercise occurred in seven of 43 children with reproducible exercise-induced asthma. As biphasic allergen-induced asthma is associated with a prolonged increase in nonspecific bronchial hyperreactivity, this effect was not sought in the 43 asthmatic children. There was no significant change in methacholine PD20 FEV1 before and after exercise challenge, either in children who had early, or early and late, exercise responses. Late reactions after allergen exposure are likely to be of considerable clinical significance in relation to the enhancement of bronchial responsiveness. It is reassuring that this is not the case for exercise challenge, as it would have major implications in relation to the recommendations that asthmatics should participate in normal activities and even in training programs. Furthermore, it suggests that there are differences between the pathophysiology of asthma induced by exercise and that produced by allergens. PMID- 2221486 TI - Oral gold therapy in steroid-dependent asthma, nasal polyposis, and aspirin hypersensitivity. AB - Eight patients are described who fulfill the criteria for the triad of asthma, nasal polyposis, and aspirin hypersensitivity who have been treated with oral chrysotherapy from 7 to 17 months. Patient diary and symptom scores reflect an overall improvement in global symptoms. Monthly pulmonary assessment (spirometry) does not indicate a significant change (improvement or deterioration) but average daily oral prednisone requirements have decreased. One of eight patients experienced a minor side effect of treatment but did not require discontinuation of therapy. Oral gold therapy may prove to be an alternative therapy in a select population of patients and permit a reduction or discontinuation of oral corticosteroid therapy. PMID- 2221487 TI - Dust mite assays in clinical allergy practice: mite antigen exposures among skin test positive patients in Kansas. AB - We have attempted to determine whether sensitive monoclonal antibody assays for Dermatophagoides mite antigens Der p I and Der f I can be carried out in a private clinical allergy practice laboratory, to ascertain incidence of significant home mite exposure in dust samples from patient homes in Kansas, and to consider whether such information impacts on patient management. We analyzed 152 dust samples from 62 patient homes. All patients were skin prick test positive for one or both common mite species available for skin testing, and had potentially relevant histories. Der p I and Der f I antigen levels were added together, and levels above 2 micrograms/g of dust were considered "positive." By this definition, elevated levels were found in at least one sample from 48 of 62 homes tested (77%); however, 61% of mattress samples tested, 41% of carpet samples, and 54.5% of furniture samples had levels below those considered likely to cause symptoms. Only 13 of 152 samples yielded Der p I levels above 2 micrograms/g. We conclude that monoclonal antibody assays for Der p I and Der f I antigens can be performed in a well-equipped office laboratory staffed by trained medical technologists, that Der f I is the predominant mite species in Kansas, and that data derived from mite assays may be important in treatment planning for patients suspected of having mite-related allergy symptoms. PMID- 2221488 TI - A controlled, double-blind study of the effect of quazolast on nasal challenge with ragweed antigen. AB - Quazolast is a potent mediator release inhibitor as determined by in vitro and in vivo testing. A placebo-controlled, double-blind, two-way crossover study compared the safety and efficacy of Quazolast, 400 mg bid orally, with placebo in 23 subjects with ragweed (RW) allergy, out of season. Subjects were assigned to two 7-day treatments in a random sequence with an 8-day washout. Subjects were challenged on days 1 and 7 of each trial with serial dilutions (10, 100, 1000, 1350, and 2700 PNU/0.135 mL) of RW, using metered pump spray bottles, (two sprays delivered 0.135 mL), preceded by saline control. Efficacy evaluation consisted of nasal flow rates measured by rhinomanometry, sneeze counts, nasal itchiness scores, and weight of nasal secretions during challenges. During Quazolast treatment, subjects had significantly lower (P less than .05) mean percent decreases in nasal flow rate at 1350 and 2700 PNU. Nasal itchiness scores were significantly lower (P less than .05) during Quazolast treatment than at placebo at 1000, 1350, and 2700 PNU. Although sneeze counts were lower during treatment with Quazolast than with placebo, the results did not reach statistical significance. No significant improvement was seen in the weight of nasal secretions. Adverse experiences, clinical laboratory results, and physical examinations were unremarkable, posttreatment. Quazolast was superior to placebo in protecting against nasal congestion and nasal itchiness after ragweed nasal challenge. PMID- 2221489 TI - Effect of exercise on complement activity. AB - Complement measurements of C1, C1q, C2, C3, C4, C5; the anaphylatoxins, C3a, C4a, and C5a; and total hemolytic activity of the classical and alternative pathways were made in 26 experienced adult runners before and after shortterm aerobic exercise. The baseline results were compared with those of nonexercising age matched controls. In most subjects tested, running resulted in nanogram increases in C3a and C4a with corresponding decreases in the hemolytic activity of C4 (C4H). Baseline values of C3 and C4H were decreased significantly in runners when compared with nonexercising controls. Preliminary studies measuring the effect of exercise on C3a levels were also done in three asthmatic runners. Mean resting and postexercise levels, and exercise-induced increases in C3a anaphylatoxin in the asthmatic subjects were significantly higher than in the nonasthmatic subjects. The findings indicate that short-term exercise results in the activation of C3 and C4 and subsequent generation of C3a and C4a anaphylatoxins, and suggest that both activation of the classical pathway of complement and a selective downregulation of C3 production may occur in persons regularly engaged in aerobic exercise. The exaggerated generation of C3a by asthmatic subjects during exercise raises the possibility that anaphylatoxins play an etiologic role in exercise-induced asthma. PMID- 2221490 TI - Effect of vitamin C on histamine bronchial responsiveness of patients with allergic rhinitis. AB - The effect of acute oral administration of 2 g vitamin C on bronchial responsiveness to inhaled histamine in 16 patients with allergic rhinitis was compared with placebo on two consecutive days in a double-blind, crossover design. The PC15FEV1 was significantly increased one hour after treatment with vitamin C but not after placebo. PMID- 2221491 TI - Topical capsaicin induces cough in patient receiving ACE inhibitor. PMID- 2221492 TI - Spacers for childhood asthma. PMID- 2221493 TI - [Study of the complement system. General principles and perspectives]. AB - Measurement of complement in clinical medicine is traditionally based on the determination of CH50 and immunochemical and/or functional measurement of complement proteins C1q, factor B, C3 and C4. The interpretation of these measurements, as far as complement activation is concerned, can however be difficult as these tests do not allow to discriminate between consumption due to activation, hereditary deficiency, increased rate of synthesis or even hyposynthesis. This explains why their use as markers of evolutivity in diseases where complement activation is occurring has given variable results. New tests for complement activation have been more recently introduced. These are mainly the measurements of the anaphytotoxins, the degradation products of C3 and the membrane attack complex. As these tests reflect more directly complement activation, they may be more reliable markers. The immunochemical and functional measurements of C1-inhibitor are of special interest as they are the tests which allow definitive diagnosis of the hereditary angio-oedema. General principles for the interpretation of the different tests used to evaluate the complement system are presented and discussed. PMID- 2221494 TI - [Antibody interference in immunoassays with markers]. AB - Antibody interferences in competitive and non-competitive immunoassays are discussed for analyte specific and reagent specific (anti-antibodies) antibodies. The effect on apparent measured concentrations is described and the methods to detect and, when possible, to eliminate these interferences are reported. PMID- 2221495 TI - [Application of the immunoenzyme technic in double determination of antibodies for the study of hyperlipoproteinemia]. AB - Antibodies directed against designed apolipoprotein, were absorbed on microtiter plates, the other apolipoprotein present on the retained particles was evaluated by using corresponding peroxidase labeled antibodies. This differential antibody immunosorbent assay was applied to evaluate lipoprotein particles concentration in familial type IIa, IIb, III, IV, and in the type IV secondary to chronic renal failure. Type IIa and IIb, were characterized by the increasing plasma concentration of lipoprotein particles containing both apo B and apo E (LpE-B). Although type IIa have high level of apo CIII, the plasma concentration of lipoprotein containing both apo B and apo CIII was within the normal range. The high concentration of apo E in type III hyperlipoproteinemia, revealed the accumulation of LpB-CIII-E but mainly lipoproteins containing both apo B and apo E (LpE-B). The latter represents 0.94 +/- 0.51 g/l when compared to normolipidemic subjects: 0.29 +/- 0.06 g/l. The decrease concentration of apo AI affects essentially lipoprotein containing apo AI without apo AII (LpAI) in primary type IV hyperlipoproteinemic patients, while in chronic renal failure, both populations of apo AI (with and without apo AII) were affected. The differential antibody immunosorbent assay may be used in the future as a new approach to classify lipid transport disorders. PMID- 2221496 TI - [Evaluation of ELISA using A60 antigen from Mycobacterium bovis BCG: specific IGG and IGM in mycobacterial infections]. AB - The authors have evaluated an ELISA (A60-Tb, Anda biologicals) allowing the detection of specific IgG and IgM against A60 antigen from Mycobacterium bovis BCG during mycobacterial infections. This study included sera from 110 african subjects and from 71 French subjects distributed in 4 clinical groups: 55 tuberculous patients (I), 41 leprous patients (II), 33 pneumopathies (III) and 52 healthy subjects (IV). Serological results were compared taking as reference for the diagnosis of tuberculosis the positivity of culture and/or that of a direct examination, and for leprosy the positivity of a direct examination associated either with a Mitsuda's reaction or with an histopathological examination. IgG were found to be more discriminative than IgM. Considering together the results of groups I and II, the authors found a sensitivity of 95.8 p. cent and a specificity of 75.3 p. cent with threshold of 200 U/ml for specific IgG. Anti-A60 antigen antibodies obtained for groups I and II were significantly higher (IgG: p less than 0.0001; IgM: p less than 0.001) than those observed in other groups. African subjects presented IgG titers higher than those obtained by French subjects (p less than 0.0001). IgM response was more frequent among group II (97.6 p. cent) than group I (21.8 p. cent). However, IgG (26.9 p. cent) and IgM titers (30.8 p. cent) were detected among group IV. This test would allow a control of therapeutic efficacy with an additional interest for classifying borderline forms of leprosy. PMID- 2221497 TI - [Accuracy in thyroid hormonology: evaluation of free T4 by five immunometric methods using cold markers]. AB - During a comparative multicentric evaluation, five commercially available non isotopic methods for FT4 measurement were tested. As with the radioactive methods the problem with accuracy is again evident. This is true both for setting reference values and standards as well as for the specificity of the methods. The authors demonstrated highly significant correlations as described in recent papers: many of the values may, however, be up to double value in one center compared to another despite the correlation of 0.90. PMID- 2221498 TI - [Study of lymphocytes T chromosome aberrations in painters exposed to genotoxic risk]. AB - Chromosomal aberrations test was applied to 12 chemically exposed painters and 13 occupationally non exposed subjects. The results showed a significant increase of heritable chromosomal aberrations level (chromatid breaks and chromatid gaps) in painters. The authors discussed the applicability of this test of the occupational health. PMID- 2221499 TI - Dry chemistry thin film immunoassay. AB - The authors report the development of a novel thin film multilayer immunoassay technology. The technology is applied to therapeutic drug monitoring and thyroid hormone testing in serum or plasma and can be extended to assays of other low molecular weight analytes. The assay detection range spans five orders of magnitude, from 1 x 10(-3) to 1 x 10(-8) M. The assay element comprises of multilayer coated chip, containing the active reagents in an agarose matrix and a plastic module serving both as a holder and a spreader. The assays are in the fluorescent competitive immunoassay format of the ligand displacement mode and are performed on an automated instrument with random access capability. The assays are fast and reliable and gave very good agreement when compared to reference methods. PMID- 2221500 TI - The "soluble sandwich" approach for immunoassays: methodological and instrumental implications. AB - The simultaneous presence of homogeneous and heterogeneous reactions at different binding sites of a multiepitope antigen makes the description of the kinetic parameters of the so called "one step" solid phase immunometric assays complex. The authors extended the "one step" approach to the concept of the "soluble sandwich" methodology which differs from the former by the delayed solid phase capture of the biotinylated immunocomplex to a streptavidin coated solid support. Using prolactin monoclonal IEMAs as a model, the equilibria involved in the reactions have been studied on a thermodynamic basis through a description of the kinetics of the interactions between biotinylated Mabs and solid phase streptavidin both in presence and/or in absence of the antigen and HRP-conjugated antibody. A comparative evaluation of models in which the biotinylated antibody was previously insolubilized on the streptavidin solid phase has been performed as well. The experimental work was carried out by using 125I labelled McBiot and Prolactin to trace individual interactions and peroxidase/H2O2/TMB systems to develop the enzymatic analytical signals. A new instrument/data reducing system was also optimized to expand the OD reading range provided by conventional, single wavelength colorimeters. The greater flexibility theoretically expected for the "soluble sandwich" approach and the possibility to extend the analyte working range without detrimental effects on the readability of low doses responses have been experimentally confirmed. PMID- 2221501 TI - Amplifiable hybridization probes. AB - Amplifiable hybridization probes enable the development of extremely sensitive clinical assays. These novel molecules consist of a probe sequence embedded within the sequences of a replicatable RNA. The molecules are first hybridized to target sequences in a conventional manner. The probe-target complexes are then isolated and the probes are released from their targets. The released probes are then amplified by incubation with the RNA-directed RNA polymerase, Q-beta replicase. The replicase copies the probes in a geometrically increasing manner: after each round of copying, the number of RNA molecules is twice the previous number. The doubling process is very rapid, resulting in as many as one billion copies of each molecule in 30 minutes. The amount of RNA that is made is large enough to be measured without using radioisotopes. Theoretically, these assays should be extraordinarily sensitive, since only one probe molecule is required to start the amplification process. In practice the sensitivity of the assays is limited by the presence of non hybridized probes that persist, despite extensive washing of the probe-target hybrids. Currently, the limit of detection is about 10,000 molecules of target. However, replicatable probes are now being prepared that include a "molecular switch", which is a region of the RNA that undergoes a conformational change when the probe sequence hybridizes to its target. Protocols are being developed that link signal generation to the state of this switch. The simplicity and speed of the enzymatic steps that are required facilitate automation of the assays. PMID- 2221502 TI - The polymerase chain reaction in the human immunodeficiency virus diagnosis. AB - The PCR technique detects HIV1 and HIV2 DNA and RNA sequences in mononuclear cells with high sensitivity. It allows therefore to analyse the mother to child HIV1 transmission. Moreover, in the near future, the quantification of the PCR products could allow the follow-up of the patients treated for HIV infection. PMID- 2221503 TI - Experience of gas-liquid chromatography in clinical microbiology. AB - In clinical microbiology, gas-liquid chromatography (GLC) is used mainly for the following applications: (1) demonstration of microbial metabolites in cultures: studies of short-chain fatty acids (chain length 2 to 6 carbon atoms) and of the non-volatile lactic and succinic acids are the basis of taxonomy of obligate anaerobes on the genus level. Demonstration of these compounds in spent culture media is also used for identification of anaerobic bacteria in the clinical laboratory. (2) Investigation of long-chain fatty acids of cell membranes and the cell wall: analysis of fatty acids with chain lengths of 9 to 20 carbon atoms are used primarily for taxonomic purposes. A practical application for use in clinical bacteriology is the Microbial Identification System (MIS) based on equipment built by Hewlett-Packard. Although this system is excellently suited for quantitative analysis of long chain fatty acids and gives valuable preliminary or confirmative information, it often requires additional testing for identification of bacteria to species level. (3) Direct rapid diagnosis of infection: demonstration of metabolic products in body fluids can be of value in infections with anaerobes (demonstration of fatty acids) and yeasts (sugars). GLC combined with mass spectrometry or frequency-pulsed electron capture GLC techniques have been applied to studies of sera, fecal specimens, and cerebrospinal fluids. These latter applications are still in an experimental stage. However, the rapid diagnosis of tuberculosis directly from cerebrospinal fluid and sputum is well advanced. The potential of direct diagnosis without the resort to cultures warrants continued research with these techniques. PMID- 2221504 TI - Implants, transplants, and other parts of the medicine of the future. AB - Today, therapies that rely on adding something "more than natural" to the patient are a commonplace of medical practice. Although we may view such therapies as recent developments of biomedical science and engineering, they are actually the culmination of efforts to replicate, replace, and enhance parts of the human anatomy that date from the early days of recorded history. A review of some of those early efforts is an instructive way to begin. It helps us to appreciate that current developments at the forefront of biomedical science and engineering will soon transform the implants and transplants of today into the relatively primitive implants and transplants of the past. A discussion of the present state of implants and transplants follows. It is necessary to allow us to appreciate the great potential offered by current biomedical science and engineering for future developments in the therapies of the "more than natural." And then, finally, we can offer a present view of the implants, transplants, and other parts of the medicine of the future. PMID- 2221505 TI - Parametric analysis of flow in the intramyocardial circulation. AB - A simple mathematical model of the intramyocardial circulation has been utilized to provide a better understanding of coronary blood flow. The model includes three myocardial layers, each characterized by a three-parameter windkessel with one capacitance and two resistances. The effects of the beating heart are taken into account by means of an intramyocardial pump and the possible collapse of the vessels by an elevated backpressure. The three basic parameters that govern the flow are a normalized time constant, tau, the total resistance, Rt, and a parameter, alpha, which specifies the resistance distribution in the intramyocardial circulation. Both the normal beating heart and prolonged diastole have been investigated analytically as well as numerically. It is shown that each of these parameters has its own special significance. Calculated pressure-flow relationships and zero-flow pressures for the case of prolonged diastole show a high sensitivity to tau and alpha. PMID- 2221506 TI - A planar slab bidomain model for cardiac tissue. AB - A fully three-dimensional model of the ventricular or atrial free wall will involve a planar geometry of finite thickness. The governing equations for the interstitial and extracellular potential of a planar slab of cardiac tissue comprised of parallel fibers undergoing uniform plane-wave activation are presented. A comparison with a bidomain of cylindrical geometry with the same half-thickness shows that the potentials in the planar bidomain (as a function of depth) approach core-conductor behavior more quickly. PMID- 2221507 TI - Blood pressure levels and variance assessed by ambulatory monitoring: optimal parameters. AB - We obtained multiple ambulatory blood pressure monitoring (ABPM) records over five years from two trained, normotensive subjects experienced in wearing the apparatus. The resulting time series data on systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were used to suggest optimal parameters for monitoring by two instruments (Colin Medical Instruments ABPM-630 and Del Mar Avionics Pressurometer) and to compare two indirect methods (auscultatory and oscillometric). A 10-min sampling interval day and night provided sufficient density of data to support spectral analysis for ultradian rhythms in the frequency range of one cycle per hour to one cycle per 9 h on a 24 h record. Rhythms with major periods of approximately 3, 6, and 9 h were variously found in 94 normotensive subjects, aged 20 to 95 years, including the two trained subjects. When the monitoring period was extended to 72 h, the circadian (approximately 24 h) rhythm could be more sharply defined, as well as a 12-h harmonic. In some studies the two trained subjects wore two monitors, one on each arm, set to read simultaneously. From the simultaneous measurements on both arms, it was shown that averaging across three points (30 min of record) reduced the coefficient of variation between the two simultaneous records to 6% or less. Auscultatory and oscillometric methods were equally reliable. Echocardiographic data were obtained in five normotensive subjects and compared to their ABPM data. The ABPM records provided additional information about cardiovascular function not merely duplicating that obtained by acute stress tests, such as exercise or cold pressor responses, or echocardiography. Standards for ABPM are suggested. PMID- 2221508 TI - Imbalanced biphasic electrical stimulation: muscle tissue damage. AB - The effects of imbalanced biphasic stimulation were studied on cat skeletal muscle to determine if greater charge densities can be safely used than with balanced or monophasic stimulation. The results of the study indicate that imbalanced biphasic stimulation can be tolerated safely by tissue at or below a net dc current density of 35 microA/mm2 and not safely tolerated at or above a net dc current of 50 microA/mm2. Monophasic stimulation has been shown to be safe at or below net dc current levels of 10 microA/mm2 and in these studies we found it was not safe at or above net dc current levels of 20 microA/mm2. Stimuli were applied to muscles via coiled wire intramuscular electrodes using a regulated current source. Since the safe average current density was higher for imbalanced biphasic stimulation than for monophasic stimulation, this suggests that: (a) pH change is not the primary reaction causing tissue damage and (b) the damaging electrochemical process that takes place during a cathodic stimulation pulse can be reversed by an anodic pulse having substantially less charge than its companion cathodic pulse. We conclude that greater cathodic charge densities can be safely employed with imbalanced biphasic stimulation than with either monophasic stimulation or balanced charge biphasic stimulation. PMID- 2221509 TI - Temporal aggregate size distributions from simulation of platelet aggregation and disaggregation. AB - A modification of the Smoluchowski collision theory for platelet aggregation is proposed with additional kinetic terms to accommodate observed disaggregation behavior. This model, consisting of a set of coupled, nonlinear, first-order differential equations, approximates size distributions with time for normal human platelets in plasma after the addition of a stimulus. Parameters controlling the kinetics of the formation and breakup of aggregates are numerically investigated. The aggregation coefficient, predominant during the aggregation phase, is strongly dependent on both time and aggregating agent doses. For the disaggregation phase, the disaggregation rate constants are a function of aggregate size, with a time-dependent disaggregation coefficient. Numerical results generated by the model are compared with experimental volume size distribution curves from the literature. PMID- 2221510 TI - Analysis and prediction of left ventricular performance under load changes during cardiac catheterization. AB - The applicability of a computer model, which relates the transmural mechanical distribution in the left ventricle (LV) to its global function at different loading conditions, was evaluated in patients with normal to near normal LV function undergoing cardiac catheterization. Left ventriculography and measurements of aortic and LV pressures were performed at baseline conditions and repeated following rapid volume expansion with intravenous infusion of 250 to 300 ml of physiologic saline and also after sublingual isosorbide-dinitrate (ISDN) administration. Twenty patients (18 men and 2 women, average age = 53 years) underwent coronary angiography and left ventriculography. Sixteen patients had coronary artery disease with one- to three-vessel involvement and 4 had normal coronary arteries. The measured input data into the model included the end diastolic LV volume and wall thickness, aortic pressure, heart rate, and the peripheral resistance. The model parameters of myocardial contractility and arterial system capacitance for the control baseline conditions were estimated so that an accurate match was obtained between the predicted and the measured end systolic (ES) volume and pressure. Using these parameters, model predictions for the two load perturbations were compared to the measurements. An excellent correlation was found between the predicted and measured LV ES volumes and peak systolic pressures (PSP) (R2 greater than 0.994). In four patients, who developed ischemic symptoms during saline injection, the prediction of end-systole volumes were lower than the measured values, suggesting an actual reduction in contractility during acute ischemia. Therefore, the model is sensitive to contractility changes. The model predicts global LV performance, under different loading conditions, including stroke work, peak developed wall stress, velocity of fiber shortening, and myocardial oxygen consumption. PMID- 2221511 TI - A comparative trial of three agents in the treatment of acute migraine headache. AB - STUDY OBJECTIVES: A study was conducted to evaluate the relative efficacy of three non-narcotic agents, chloropromazine, lidocaine, and dihydroergotamine, in the treatment of migraine headache in an emergency department setting. DESIGN: The trial was randomized and single blinded. SETTING: The study was conducted in two university-affiliated EDs. TYPE OF PARTICIPANTS: All patients had an isolated diagnosis of common or classic migraine. INTERVENTIONS: Patients were pretreated with 500 mL (IV) normal saline before randomization. Study drugs as administered were dihydroergotamine 1 mg IV repeated after 30 minutes if the initial response was inadequate; lidocaine 50 mg IV at 20-minute intervals to a maximum total dose of 150 mg as required; or chloropromazine 12.5 mg IV repeated at 20-minute intervals to a total maximum dose of 37.5 mg as required. Patients were asked to grade headache severity on a ten-point scale before and one hour after the initiation of therapy. Follow-up by phone was sought the following day. MEASUREMENTS AND MAIN RESULTS: Of 76 patients completing the trial, 24 were randomized to receive chloropromazine, 26 to receive dihydroergotamine, and 26 to receive lidocaine. Reduction in mean headache intensity was significantly better among those treated with chloropromazine (P less than .005). Persistent headache relief was experienced by 16 of the chloropromazine-treated patients (88.9%) contacted at 12 to 24 hours follow-up compared with ten of the dihydroergotamine treated patients (52.6%) and five of the lidocaine-treated group (29.4%). CONCLUSION: The relative effectiveness of these three antimigraine therapies appears to favor chloropromazine in measures of headache relief, incidence of headache rebound, and patient satisfaction with therapy. PMID- 2221512 TI - A prospective, double-blind study of metoclopramide hydrochloride for the control of migraine in the emergency department. AB - STUDY OBJECTIVE: To determine the effectiveness of IV metoclopramide as sole therapy for relieving the pain of acute migraine in the emergency department. DESIGN: Prospective study. Fifty patients were divided randomly into subjects and placebo controls with blinding of the treating physician and the patient. PARTICIPANTS: Patients presenting to the ED with migraine requiring parenteral treatment. INTERVENTIONS: Subjects received 10 mg IV metoclopramide and controls received IV normal saline; patient assessment of relief was followed by means of a numerical scale. MEASUREMENTS AND MAIN RESULTS: Sixty-seven percent of subjects compared with 19% of controls had effective pain relief within one hour (P less than .001). Subjects achieved mean relief scores of 2.46 compared with 1.69 for controls (P less than .02). No significant side effects were observed. CONCLUSION: IV metoclopramide as a single agent is effective and safe therapy for migraine in the ED. PMID- 2221513 TI - An evaluation of cocaine-induced chest pain. AB - STUDY OBJECTIVE: To determine if enzymatic evidence of acute myocardial injury is present in patients complaining of chest pain after cocaine use when the ECG is normal or nondiagnostic. DESIGN: Serial ECG and creatinine kinase (CK) and CK isoenzymes (CK-ISO) determinations were performed at time of emergency department presentation and every six hours over 12 hours on individuals complaining of chest pain within six hours of last cocaine use. SETTING: ED of an urban tertiary care center. TYPE OF PARTICIPANTS: Forty-two individuals with a mean age of 28.5 years. INTERVENTIONS: Patients with positive CK-ISOs were admitted immediately to formally rule out myocardial infarction. Patients developing ECG changes during observation period also were admitted even if CK-ISOs were normal. Patients with unchanged ECGs and normal CK-ISOs were discharged after 12 hours of observation. RESULTS: Eight patients (19%) had elevated CK and CK-ISO values at presentation. Two of these patients had elevated values on three sequential determinations and were believed to have sustained acute myocardial infarction. Six patients had elevated CK and CK-ISOs at presentation only. ECGs remained normal or nondiagnostic in all patients. CONCLUSIONS: Enzymatic evidence of acute myocardial injury may occur in patients who develop chest pain after cocaine use and have normal or nondiagnostic ECGs. This injury may reflect acute infarction or transient ischemia. Single or serial normal or nondiagnostic ECGs do not rule out ischemia or injury in this group of patients. PMID- 2221514 TI - Treatment of moderate-to-severe hypothermia in an urban setting. AB - STUDY OBJECTIVES: To study the treatment of moderate-to-severe hypothermia using a combination of core rewarming techniques. DESIGN: A prospective study. SETTING: The emergency department of an urban, community hospital. TYPE OF PATIENTS: Sixteen patients who presented with accidental hypothermia with a core temperature of less than 32 C. INTERVENTIONS: All patients were treated with warmed IV fluids either through central or peripheral IV lines and heated aerosol masks. MEASUREMENTS AND MAIN RESULTS: The patients had a mean rewarming rate of 1.16 C/hr; all survived. The majority were chronic alcoholic patients who presented with multiple medical conditions that required hospitalization. CONCLUSION: All patients recovered with this method of core rewarming. PMID- 2221515 TI - Emergency department diagnosis of ectopic pregnancy. AB - STUDY OBJECTIVES: To assess the accuracy of the history and physical examination as compared to the addition of serum progesterone screening for ectopic pregnancy in women presenting to the emergency department. DESIGN: Prospective, consecutive case series, N = 2,157. SETTING: ED of the Regional Medical Center at Memphis, a publicly subsidized, 450-bed acute care hospital staffed by residents and faculty of the University of Tennessee, Memphis. TYPE OF PARTICIPANTS: All ED patients with a positive urine pregnancy test treated between January 1 and December 31, 1988. INTERVENTIONS: Screening history, physical examination, and serum progesterone (P) and quantitative human chorionic gonadotropin (hCG) titer. MEASUREMENTS: All discharged patients were given follow-up appointments within two weeks; those found to have a P less than 25 ng/mL were called to return for repeat hCG and transvaginal ultrasound. MAIN RESULTS: One hundred sixty-one of 2,157 patients (7.5%) with a positive urine pregnancy test were found to have an ectopic pregnancy. All but five had a P of less than 25 ng/mL (sensitivity, 97%); four of these were admitted for immediate surgery because of symptoms. Overall, the ED physician detected 89 of 161 ectopics (55.3%) on initial presentation, 53 (60%) of which were ruptured at the time of surgery. Seventy-two patients (44.7%) who were discharged but later found to have an ectopic pregnancy had benign clinical presentations, including 41 with vaginal bleeding. There were no statistically significant differences in the presenting symptoms of patients with unruptured ectopics compared with normal intrauterine pregnancies. All but one of the 72 discharged patients were noted the following day to have a progesterone of less than 25 ng/mL and contacted to return. Eight of these were found to have a ruptured ectopic at the time of surgery. Only 91 of 161 patients (56.5%) with ectopic pregnancy acknowledged one or more clinical risk factors on follow-up questioning. CONCLUSION: The standard history and physical examination, including those performed by gynecologic specialists, are insufficiently sensitive for early detection of unruptured ectopic pregnancy. EDs with a high incidence of ectopic pregnancy should strongly consider implementation of a universal progesterone screening program to decrease unnecessary patient morbidity and the risk of mortality from undiagnosed ectopic pregnancy. PMID- 2221516 TI - Brain water content, brain blood volume, blood chemistry, and pathology in a model of cerebral edema. AB - STUDY OBJECTIVES: The objective was to correlate regional changes during brain water content with alterations in blood chemistry and cerebral pathology during hypo-osmotic edema. PARTICIPANTS: Sprague-Dawley male adult rats were used in these studies. DESIGN: Animals were block-randomized to receive either an intraperitoneal distilled water injection equivalent to 5% or 15% of their body weight or no injection (controls). Rats were sacrificed 15 or 60 minutes after water injection or at an equivalent time for controls. INTERVENTIONS: No interventions were performed. MEASUREMENTS AND MAIN RESULTS: Water content of cerebral cortical gray and white matter was calculated from measurements of tissue specific gravity. Blood plasma osmolality and sodium and potassium concentrations were determined at various times after water injection. An index of blood-brain barrier permeability was obtained by measuring brain red blood cell and plasma volumes. A qualitative assessment of edema was made from light and electron micrographs of the cerebral cortex. We found that water injection produced a dose-dependent decrease in plasma osmolality and sodium concentration within 15 minutes. Cortical water content was unchanged after this period. An influx of water into cerebral gray, and, less readily, into cerebral white matter occurred during the next 15 minutes. Whole blood specific gravity and brain blood content were unchanged and thus did not confound the measurement of cerebral water content. Hematocrit was increased 60 minutes after a 15% water injection. The blood-brain barrier remained intact throughout this period. Microscopy revealed astrocytic swelling with slight extracellular fluid accumulation 60 minutes after the water injection. CONCLUSIONS: Homeostatic mechanisms in the cerebral cortex can maintain constant water content for at least 15 minutes during maintained intravascular hypo-osmolality. Fluid that subsequently moves into the tissue primarily enters an intracellular compartment. This model will be useful in investigating physiological mechanisms of brain water regulation and the pathogenesis of brain edema, a common clinical entity in emergency conditions. PMID- 2221517 TI - Improved survival and reduced myocardial necrosis with cardiopulmonary bypass reperfusion in a canine model of coronary occlusion and cardiac arrest. AB - STUDY QUESTION: Does cardiopulmonary bypass (CPB) improve resuscitation rates and limit infarct size after cardiac arrest and acute myocardial infarction? DESIGN: Controlled randomized trial with all animals undergoing left anterior descending coronary artery occlusion and subsequent ventricular fibrillation and resuscitation. All animals were supported for four hours after resuscitation in an intensive care setting. INTERVENTION: Group 1 (eight) was resuscitated with standard external CPR and advanced life support. Group 2 (eight) was resuscitated with CPB. MEASUREMENTS AND MAIN RESULTS: Group hemodynamic, resuscitation variables, number resuscitated, and number of four-hour survivors were compared. Ischemic and necrotic myocardial weights were determined with histochemical staining techniques in four-hour survivors. Infarct size was measured as the ratio of necrotic weight to ischemic weight. Significantly fewer dogs were resuscitated in group 1 (four of eight) than in group 2 (eight of eight) (P less than .05). Group 2 survivors required significantly less epinephrine and lidocaine than group 1 survivors (P less than .05) and higher aortic diastolic and coronary perfusion pressures after CPB (P less than .001). The ratio of myocardial necrotic weight to ischemic weight at four hours was 0.82 +/- 0.25 in group 1 and 0.22 +/- 0.25 in group 2 (P less than .05). However, collateral blood flow was not measured in this study. CONCLUSION: This pilot study further substantiates the improvement in resuscitation rates obtainable with CPB. CPB may also limit infarct size during the postresuscitation period and requires further study. PMID- 2221518 TI - Interaction between whole-bowel irrigation solution and activated charcoal: implications for the treatment of toxic ingestions. AB - STUDY OBJECTIVES: The purpose of this study was to address the issues of safety and efficacy of combining whole-bowel irrigation and activated charcoal administration for the treatment of toxic ingestions. STUDY DESIGN: Two in-vitro studies were performed. In the first, serial ratios of polyethylene glycol (PEG) and activated charcoal (AC) powders were added to water and the solutions were analyzed for PEG concentration and osmolality. In the second, serial ratios of a pharmaceutical bowel irrigation solution and an AC preparation were combined with a constant amount of salicylic acid. Solution osmolalities, PEG, and salicylic acid concentrations were then quantified. RESULTS: Adsorption of PEG powder by AC was demonstrated; however, changes in solution osmolality were negligible. Thus, concurrent administration of these therapies appears safe. However, combining bowel irrigation solution with AC resulted in decreased salicylic acid adsorption. This was especially so with smaller amounts of AC that would pertain more to the smaller doses of AC used for multiple-dose charcoal therapy. CONCLUSION: If these in-vitro data are applicable to overdose patients, the administration of a routine initial charcoal dose to those who will be treated with whole-bowel irrigation would be appropriate. However, it is unlikely that the addition of multiple-dose charcoal therapy to whole-bowel irrigation would provide additional benefit for the patient. PMID- 2221519 TI - Clinical evaluation of an acetaminophen meter for the rapid diagnosis of acetaminophen intoxication. AB - STUDY OBJECTIVES: To test the accuracy of a newly developed meter that determines serum acetaminophen concentration after a 30-second analysis of one drop of whole blood. DESIGN: Sixty-six blood samples from patients with known or suspected drug overdose were analyzed for the presence of acetaminophen. In all cases determination of serum acetaminophen concentration was performed simultaneously with the meter and by a reference laboratory. SETTING: Eligible patients were those who presented during a nine-month period to the emergency departments of two tertiary care hospitals (including a pediatric hospital). RESULTS: Thirty-one specimens had a laboratory-confirmed detectable acetaminophen concentration. The meter identified these toxic specimens in all cases; there were no false negatives (sensitivity, 100%). Among the 35 specimens not containing acetaminophen, the meter invariably confirmed a nondetectable serum acetaminophen concentration (specificity, 100%). Acetaminophen measurements by the meter correlated strongly with laboratory determinations (r = .985, P less than .001). Repeated testing of one specimen documented the precision and reproducibility of the meter's analysis; mean coefficient of variation was .08 in measuring toxic acetaminophen concentrations. Drug coingestion had no significant effect on the accuracy of the meter. Instrument accuracy was maintained after more than 100 uses without recalibration. CONCLUSIONS: This meter identifies the possibility of rapid and accurate determinations of serum acetaminophen concentration. The instrument is ideally suited for patients with acetaminophen poisoning in whom expeditious and appropriate administration of antidotal therapy is desired. PMID- 2221520 TI - Predicting the severity of cocaine-associated rhabdomyolysis. AB - STUDY OBJECTIVES: The syndrome of rhabdomyolysis associated with cocaine use has been recently described, but the incidence, severity, risk factors, and complications are unknown. This study sought to describe the spectrum of the syndrome and identify clinical features of patients at risk. DESIGN: Retrospective case series with analysis of common clinical features. SETTING: Medical emergency department of an urban teaching hospital serving an indigent population. TYPES OF PARTICIPANTS: ED patients with acute cocaine intoxication and a serum creatine kinase (all MM) of more than 500 U/L (8.3 ukat/L) who were admitted for in-hospital management. MEASUREMENTS AND MAIN RESULTS: Twenty-nine patients, representing 5% of cocaine-related patient visits, were identified over 20 months. Patients were divided into three groups: mild, characterized by anxiety, tachycardia, diaphoresis, dyspnea, or chest pain; moderate, characterized by delirium, agitation, fever, leukocytosis, or an elevated serum creatinine; and severe, characterized by seizure, coma, hypotension, arrhythmia, or cardiac arrest. There was a significant association between the rating system for level of intoxication and the severity of rhabdomyolysis and its complications (P less than .01). Patients at highest risk for complications of rhabdomyolysis were those in the moderate or severe groups. CONCLUSION: This classification system may be useful for the management of patients with acute cocaine intoxication, predicting those patients in whom aggressive therapy should be initiated in the ED to minimize the complications of rhabdomyolysis. PMID- 2221521 TI - The effect of activated charcoal on phenytoin pharmacokinetics. AB - STUDY OBJECTIVES: To examine the effect of administration of oral activated charcoal with or without sorbitol on the elimination of phenytoin. SETTING: Emergency department of a rural teaching institution. TYPE OF PARTICIPANTS: Eight normal volunteers. INTERVENTIONS: Subjects received 15 mg/kg phenytoin as an IV infusion. During the first phase of the study, oral activated charcoal was administered to a total dose of 140 g over a ten-hour period. During the second phase of the study, phenytoin alone was administered. MEASUREMENTS AND MAIN RESULTS: Administration of activated charcoal resulted in a significant decrease in the area under the curve 0-inf (p = .008) and in total body clearance (P = .008). No difference in the effect on phenytoin pharmacokinetic parameters was noted when the charcoal was administered with or without sorbitol, but fewer gastrointestinal adverse effects were noted without sorbitol treatment. CONCLUSION: Oral activated charcoal was shown to affect phenytoin pharmacokinetic parameters. Further pharmacokinetic/pharmacodynamic studies are warranted to determine if activated charcoal results in a faster recovery from phenytoin toxicity. PMID- 2221522 TI - Transcranial Doppler determination of cerebral perfusion in patients undergoing CPR: methodology and preliminary findings. AB - STUDY OBJECTIVES: To correlate cerebral arterial blood velocity measurements as determined by transcranial Doppler ultrasound with various resuscitation maneuvers performed in an uncontrolled manner in a series of cardiac arrest patients undergoing standard resuscitation. TYPE OF PARTICIPANTS: Any patient undergoing resuscitation for a nontraumatic cardiac arrest was eligible for the study. INTERVENTIONS: Resuscitation was carried out while flow velocities were monitored in various intracranial arteries by transcranial Doppler ultrasound. Vessel identification was based on the angle and depth of insonation. MEASUREMENTS AND MAIN RESULTS: The internal carotid artery was located more consistently than either middle cerebral or ophthalmic arteries and provided superior waveforms for analysis. Alterations in flow velocity were noted and correlated to various therapeutic interventions. Flow velocities were 70% of normal during the early phase of resuscitation but deteriorated over time until there was no evidence of net forward flow. Even early in CPR, flow was demonstrated only during systole. CONCLUSION: Transcranial Doppler ultrasound appears to be a potentially promising means of determining cerebral flow in patients undergoing CPR. PMID- 2221523 TI - A model preclinical, clinical, and graduate educational curriculum in emergency medicine for medical students and rotating residents. AB - The Society for Academic Emergency Medicine model curriculum for medical students and rotating residents was developed over a two-year period. The document was created as a complementary work to the undergraduate Core Content to provide appropriate emphasis, structure, and suggestions on the teaching of emergency medicine core curriculum topics at all levels. Consensus on the curriculum contents was reached from a national sample of emergency medicine educators. An educational matrix format was used to enhance flexibility based on the educational level of the learner and the instructional strengths of the teacher, and allowing for incorporation of a problem-based learning format. An outline of document contents and representative samples from each section are included; the entire document is available from SAEM. PMID- 2221524 TI - Methylene iodide poisoning. AB - A 20-month-old girl ingested a maximum of 25 mL of pure methylene iodide. Within two hours, the patient exhibited lethargy and incoordination and vomited. An abdominal radiograph demonstrated the radiopaque material in the gut. In vivo conversion to carbon monoxide was documented with a peak carboxyhemoglobin level of 14.2% reached at 11 hours after ingestion. Two days after ingestion, evidence of hepatotoxicity was apparent, and fulminant hepatic failure quickly ensued. Despite aggressive supportive care and transfer to a liver transplant center, the patient died nine days after ingestion. Methylene iodide ingestion has not been previously reported in human beings. This case verifies that this substance is a potent hepatotoxin, is metabolized to carbon monoxide in vivo, is radiopaque, and may cause bone marrow suppression. PMID- 2221525 TI - Castor bean intoxication. AB - We report the cases of a child who ingested two or more castor beans and two adults who each ingested four beans. All three patients developed severe gastroenteritis and recovered without sequelae after receiving IV fluids. The literature contains reports of 424 cases of castor bean intoxication. Symptoms of intoxication include acute gastroenteritis, fluid and electrolyte depletion, gastrointestinal bleeding, hemolysis, and hypoglycemia. Delayed cytotoxicity has not been reported. Of the 424 patients, 14 died (mortality rates: 8.1% of untreated and 0.4% of treated). Deaths were due to hypovolemic shock. Recommended treatment for asymptomatic patients who have chewed one or more raw beans is emergency department evaluation, gastric decontamination, administration of activated charcoal, observation until four to six hours after ingestion, and discharge instructions to return if symptoms develop. After decontamination and activated charcoal, symptomatic patients require hospitalization for treatment with IV fluids, supportive care, and monitoring for hypoglycemia, hemolysis, and complications of hypovolemia. Monitoring for delayed cytotoxicity is unnecessary. Castor beans and their dust are highly allergenic and may cause anaphylaxis. PMID- 2221527 TI - The strengths & weaknesses of undergraduate education. PMID- 2221526 TI - The role of undergraduate education in emergency medicine. PMID- 2221528 TI - Strong foundations for undergraduate education. PMID- 2221529 TI - Refusal of care: the ethical dilemma. PMID- 2221530 TI - Nurses drive public health: serving the public good is their goal and their focus. PMID- 2221531 TI - Public health nurses at work. PMID- 2221533 TI - Challenges confront public health. PMID- 2221534 TI - Public health nurses speak out. PMID- 2221532 TI - Physician advises RNs to leverage their power. Interview by Patricia McCarty. PMID- 2221535 TI - VA nursing has much to offer RNs. Interview by Patricia McCarty. PMID- 2221537 TI - Regulations address H-1 Visa nurses. PMID- 2221536 TI - ANA's greatest moments remembered. PMID- 2221538 TI - ANA-PAC carries collective clout. PMID- 2221539 TI - HIV counseling--know the risks. PMID- 2221540 TI - D.C. nurses fight for public health. PMID- 2221541 TI - Public health nurses face challenges. PMID- 2221542 TI - In defense of the public health. PMID- 2221543 TI - As I see it. Convention brings profession together. PMID- 2221545 TI - Future of public health brightens. PMID- 2221544 TI - Public health nurses put caring to work. PMID- 2221548 TI - Take charge of your career. PMID- 2221547 TI - Directions. PMID- 2221546 TI - Indian Health Center fills community gap. PMID- 2221549 TI - Nursing students face liability risk, too. PMID- 2221550 TI - Programs help minority nurses earn doctorates. PMID- 2221552 TI - Be proud, caring and involved. Nurses give advice to nursing students. PMID- 2221551 TI - Back to school--what it's like. PMID- 2221553 TI - Collective bargaining benefits staff RNs. Interview by Patricia McCarty. PMID- 2221554 TI - How I became a certified nurse. PMID- 2221555 TI - Career information--get it here: organizations offer lots of information on nursing careers. PMID- 2221556 TI - ANA wins major victories on Hill for nurses, clients. PMID- 2221557 TI - Nursing career campaign attracts 49,000 callers. PMID- 2221558 TI - Board acts on health policy, AIDS statement and more. PMID- 2221559 TI - Brochure alerts RNs to liability risks. PMID- 2221560 TI - You can help shape national health policy. PMID- 2221561 TI - Self care for professionalism. PMID- 2221562 TI - As I see it. How to campaign for an ANA office. PMID- 2221563 TI - Asian-American educational achievements. A phenomenon in search of an explanation. AB - Considerable attention has been paid to the academic achievements of Asian Americans because there is convergent evidence that this population has attained high educational mobility. In trying to explain the achievement patterns, researchers have largely limited their investigations to one of two contrasting hypotheses involving (a) hereditary differences in intelligence between Asians and Whites and (b) Asian cultural values that promote educational endeavors. Research findings have cast serious doubt over the validity of the genetic hypothesis. Yet, there has been a failure to find strong empirical support for alternative hypothesis concerning cultural values. It is proposed, under the concept of relative functionalism, that Asian Americans perceive, and have experienced, restrictions in upward mobility in careers or jobs that are unrelated to education. Consequently, education assumes importance, above and beyond what can be predicted from cultural values. Research and policy implications of this view are noted. PMID- 2221564 TI - Alcohol myopia. Its prized and dangerous effects. AB - This article explains how alcohol makes social responses more extreme, enhances important self-evaluations, and relieves anxiety and depression, effects that underlie both the social destructiveness of alcohol and the reinforcing effects that make it an addictive substance. The theories are based on alcohol's impairment of perception and thought--the myopia it causes--rather than on the ability of alcohol's pharmacology to directly cause specific reactions or on expectations associated with alcohol's use. Three conclusions are offered (a) Alcohol makes social behaviors more extreme by blocking a form of response conflict. (b) The same process can inflate self-evaluations. (c) Alcohol myopia, in combination with distracting activity, can reliably reduce anxiety and depression in all drinkers by making it difficult to allocate attention to the thoughts that provoke these states. These theories are discussed in terms of their significance for the prevention and treatment of alcohol abuse. PMID- 2221565 TI - Coordination. AB - The Russian physiologist Bernstein (1967) defined coordination as a problem of mastering the very many degrees of freedom involved in a particular movement--of reducing the number of independent variables to be controlled. The initial theorizing and experimentation on "Bernstein's problem" was conducted largely in terms of how a device of very many independent variables might be regulated without ascribing excessive responsibility to an executive subsystem. A second round of theory and research on Bernstein's problem is now under way. This second round is motivated by similarities between coordination and physical processes in which multiple components become collectively self-organized; it is directed at an explanation of coordination in terms of very general laws and principles. The major achievements of the first round of efforts to address Bernstein's problem are summarized, and six examples of the theory and research typifying the second round are presented. PMID- 2221566 TI - The old homeless and the new homelessness in historical perspective. AB - In the 1950s and 1960s homelessness declined to the point that researchers were predicting its virtual disappearance in the 1970s. Instead, in the 1980s, homelessness increased rapidly and drastically changed in composition. The "old homeless" of the 1950s were mainly old men living in cheap hotels on skid rows. The new homeless were much younger, more likely to be minority group members, suffering from greater poverty, and with access to poorer sleeping quarters. In addition, homeless women and families appeared in significant numbers. However, there were also points of similarity, especially high levels of mental illness and substance abuse. PMID- 2221567 TI - Mental health services for homeless mentally ill persons. Federal initiatives and current service trends. AB - Recent research suggests that approximately one third of the population of homeless single adults suffer from severe mental illnesses. Despite multiple health, mental health, and social welfare needs, this population is often unable to obtain necessary housing and community-based services. For this reason, since 1982, the National Institute of Mental Health (NIMH) has undertaken a number of federal initiatives to encourage research and assist states and localities in improving services focused on this vulnerable subgroup of the homeless population. This article describes the target population, NIMH research findings, and current mental health service trends--with particular emphasis on two mental health programs established under the Stewart B. McKinney Homeless Assistance Act. Proposed future directions for federal research and evaluation efforts in this area are also discussed. PMID- 2221568 TI - Major mental illness, housing, and supports. The promise of community integration. AB - Providing housing and supports for people with psychiatric disabilities, particularly those who are homeless, is a major public policy challenge. This article summarizes the ways in which the concept of these needs is rapidly shifting in the mental health field. The article is based on research on the effectiveness of non-facility-based community support and rehabilitation approaches, the findings of other disability fields, and the emergence of mental health consumers' own preferences for expanded choices, normal housing, and more responsive services, including consumer-operated services. These new sources of knowledge are facilitating a paradigm shift in which people with psychiatric disabilities are no longer seen as hopeless, or merely as service recipients, but rather as citizens with a capacity for full community participation and integration. PMID- 2221569 TI - Women's health. Review and research agenda as we approach the 21st century. AB - This article reviews past research and projects future research directions regarding women's health. Sex differences in mortality and morbidity, along with evidence that the quality and quantity of these differences are changing, are examined. Over the past decade, concurrent with dramatic changes in lifestyle and social roles for women, mortality rates have shifted, resulting in a decreasing advantage for women. Explaining the consequences of these dynamic changes requires understanding the health effects of such variables as perceived control, the experience of life roles, perceived and actual social support, and redefinition of gender roles. The future portends additional changes that will significantly affect women's health. In establishing an explicit psychological research agenda on women's health, (a) general recommendations for research are provided and (b) important issues that have not yet received a great deal of research attention (e.g., women and AIDS, psychopharmacology, reproductive technologies) are highlighted. This article expands the current discourse in health psychology and raises a number of issues for serious consideration. PMID- 2221570 TI - Gay people and government security clearances. A social science perspective. AB - Lesbian and gay male applicants routinely are denied government security clearances or are subjected to unusually lengthy and intensive investigation. This article reviews social science data relevant to the principal justifications that have been offered for this policy and presents the following conclusions: (a) Lesbians and gay men are no more likely than heterosexuals to suffer from a personality disorder or emotional stress, or to be psychologically unstable; (b) lesbians and gay men are no more likely than heterosexuals to be unduly sensitive to coercion, blackmail, or duress; (c) lesbians and gay men are no more likely than heterosexuals to be unwilling to respect or uphold laws or regulations, or to be unreliable or untrustworthy. Three major flaws are discussed that underlie current government policies toward gay applicants for security clearances: (a) Groups rather than individuals are screened for undesirable characteristics; (b) applicants are rejected on the basis of problems created by government policies themselves; and (c) homosexual applicants are scrutinized according to criteria that are not applied similarly to heterosexual applicants. An alternative hypothesis, that experience with stigma actually may increase a gay applicant's ability to maintain secrecy, is discussed. Finally, some consequences of current policies are noted. PMID- 2221571 TI - Implicit memory. Retention without remembering. AB - Explicit measures of human memory, such as recall or recognition, reflect conscious recollection of the past. Implicit tests of retention measure transfer (or priming) from past experience on tasks that do not require conscious recollection of recent experiences for their performance. The article reviews research on the relation between explicit and implicit memory. The evidence points to substantial differences between standard explicit and implicit tests, because many variables create dissociations between these tests. For example, although pictures are remembered better than words on explicit tests, words produce more priming than do pictures on several implicit tests. These dissociations may implicate different memory systems that subserve distinct memorial functions, but the present argument is that many dissociations can be understood by appealing to general principles that apply to both explicit and implicit tests. Phenomena studied under the rubric of implicit memory may have important implications in many other fields, including social cognition, problem solving, and cognitive development. PMID- 2221572 TI - The hospital. Psychology's challenge in the 1990's. PMID- 2221573 TI - The practice of psychology in hospital settings. PMID- 2221574 TI - Ethical and malpractice issues in hospital practice. AB - Ethical and malpractice issues arising in hospital practice are reviewed. Topics include (a) preparation and authorization to carry out clinical responsibilities, (b) personnel procedures, (c) financial and political forces influencing hospital policies, (d) billing procedures, (e) clinical procedures for responding to patients' needs, (f) confidentiality, (g) discrimination, (h) internship and training issues, (i) sexual abuse of patients, and (j) staff conflicts influencing patient care. PMID- 2221575 TI - The psychologist as admitting clinician. A single case example. AB - An experiential view of significant issues associated with independent hospital practice for psychologists is offered through a case presentation. The example is a model of practice in effect at a 90-bed, free-standing, inpatient facility opened in 1985, that gives psychologists full professional staff privileges. PMID- 2221577 TI - The role of surfactant-associated proteins. PMID- 2221576 TI - Psychological assessment versus psychological testing. Validation from Binet to the school, clinic, and courtroom. AB - Increasingly, psychological assessment is conducted with clients and patients involved in child custody and personal injury litigation. Clinical neuropsychologists are being asked sophisticated questions by attorneys regarding the validity of practitioners' most highly respected tests. Research reviewed here bears on the validity of test-buttressed clinical opinions, including research related to the following psychometric properties of individual test scores: standard errors of measurement, test-retest stability and subtest-to subtest intercorrelations. The highest and the lowest subtest scores used as indices, respectively, of an individual's premorbid level of cognitive functioning and the degree of current impairment from that presumed earlier level is not justified when used in isolation from the life history and current medical findings. Although many practitioners use information from the wider research, courtroom experience suggests that a number do not; contrariwise, the attempt of Faust and Ziskin (1988a) to undermine the courtroom testimony of every psychologist who serves as an expert witness is also criticized. PMID- 2221578 TI - Effects of surfactant protein-A on surfactant function in preterm ventilated rabbits. AB - Surfactant protein-A (SP-A) isolated from cow surfactant was added to organic solvent extracts of natural bovine surfactant or of Survanta (Abbott Laboratories), and dynamic compliances and pressure-volume curves were measured in rabbits with a gestational age of 27 days. Organic solvent extracts of natural surfactant and Survanta significantly improved dynamic compliances and lung volumes compared with those in control rabbits, but the effects were less than for natural surfactant. Adding 1 to 10% by weight SP-A to organic solvent extracts of natural surfactant increased dynamic compliances and maximal lung volumes on pressure-volume curves to values comparable with natural surfactant. Lung volumes at 10 cm H2O on deflation curves increased in a dose-dependent fashion at concentrations of SP-A between 0.5 and 5% by weight with no further improvement at 10% SP-A, although the volumes were significantly lower than for natural surfactant. Five percent by weight SP-A did not improve any measurements for Survanta. These results indicated that SP-A favorably improved organic solvent extracted natural surfactant function in vivo. However, the responses could not be generalized to another surfactant. PMID- 2221579 TI - Inhalation of nitrogen dioxide fails to reduce the activity of human lung alpha-1 proteinase inhibitor. AB - Healthy, nonsmoking human volunteers were exposed to environmentally relevant concentrations of NO2 followed by bronchoalveolar lavage (BAL) to study whether NO2 exposure decreases the functional activity of alpha-1-proteinase inhibitor (alpha 1-PI) in the lung. Two 3-h exposure protocols with intermittent exercise were employed and BAL was performed 3.5 h after exposure. The first exposure protocol with nine subjects involved three 2-ppm "peaks" with a 0.05 ppm background, whereas the second protocol with 15 subjects was a continuous exposure to 1.5 ppm NO2. All subjects were randomly exposed to either air or NO2, with at least a 2-wk interval between treatments, and the BAL fluids obtained after air exposure served as the controls. The BAL fluids were analyzed for alpha 1-PI elastase inhibitory activity, the immunologic concentration of alpha 1-PI, total protein, and albumin. The ratio of alpha 1-PI activity to its immunologic concentration was taken as the functional activity of alpha 1-PI, and possible changes in the amount of alpha 1-PI in the lung were assessed by examining the ratio of the immunologic concentration of alpha 1-PI to total protein. Neither of the NO2 exposure protocols resulted in a decrease in the functional activity of alpha 1-PI, nor were there alterations in the immunologic levels of alpha 1-PI. These data suggest that short-term exposures to low levels of NO2 do not result in a lung-localized deficiency of active alpha 1-PI, which has been hypothesized to be a contributing factor in the pathogenesis of emphysema. PMID- 2221580 TI - Inactivation of chemotactic factor inactivator by cigarette smoke. A potential mechanism of modulating neutrophil recruitment to the lung. AB - Activation of the complement system with generation of the potent neutrophil chemotactic factor C5a has been proposed to play a significant role in the neutrophil accumulation in the lungs of cigarette smokers. Chemotactic factor inactivator (CFI) can inhibit C5a-directed neutrophil chemotaxis by binding to the C5a cochemotaxin GcGlobulin (GcG), a vitamin-D-binding protein, and inhibiting the capacity of GcG to enhance the chemotactic activity of C5a. Because cigarette smoke can inhibit the function of some proteins, a loss of CFI functional activity induced by cigarette smoke would allow an increased capacity of GcG to augment C5a-directed neutrophil chemotaxis. In order to test this hypothesis, cigarette smoke was bubbled through a CFI solution, and the solution was evaluated for its ability to inhibit the chemotactic activity of C5a and GcG. Smoke-treated CFI inhibited only 36% of the C5a-GcG chemotactic activity. In contrast, a CFI solution treated with air inhibited 62% of the chemotactic activity (p less than 0.001). Consistent with these observations, smoke-treated CFI exhibited a decreased capacity to bind to GcG and a decreased capacity to inhibit the binding of C5a des Arg to GcG. CFI contained in the bronchial lavage fluids obtained from patients with chronic obstructive pulmonary disease secondary to cigarette smoking and asymptomatic smokers exhibited a decreased capacity to inhibit C5a-GcG neutrophil chemotaxis and to bind to GcG (p less than 0.05, both comparisons). Furthermore, smoke bubbled through normal bronchial lavage fluid decreased the capacity of CFI to bind to GcG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221581 TI - Functional character and augmentation of lymphocytes in regional lymph nodes of patients with lung cancer. AB - It appears that lymph node metastases are more frequent in lung cancer than in other cancers because of impaired defensive mechanisms in the regional lymph nodes. However, little is known about the immunologic function of regional lymph node lymphocytes (RLNL) in patients with lung cancer. We have studied the immunologic properties of RLNL in comparison with peripheral blood lymphocytes (PBL). We measured the natural killer (NK) cell activity of RLNL and PBL in patients with lung cancer and found that the NK activity was significantly more depressed in the RLNL than in the PBL. In contrast, interleukin-2 (IL-2) production was markedly higher in the RLNL than in the PBL. The cytotoxic effect of RLNL in nonmetastatic lymph nodes on target cells (such as K562 cells) or PC-3 and PC-10 cells (NK-resistant, human lung cancer of adenocarcinoma and epidermoid carcinoma, respectively) was significantly enhanced by in vitro incubation with recombinant IL-2 (rIL-2). Furthermore, we clarified that both rIL-2 and OK-432, which is a biologic response modifier and IL-2 inducer as well, augmented the cytotoxicity of RLNL and that these effector cells were lymphokine-activated killer (LAK) cells. The depletion of lymphocyte subsets by pretreatment with specific monoclonal antibody showed that the LAK activity in RLNL was mediated by CD3+ and CD8+ cells, whereas the lymphocyte subsets contributing the LAK activity in PBL were CD3+ and CD16+ cells. It was concluded that a majority of the effector cells in RLNL were LAK cells of the cytotoxic T cell population. PMID- 2221582 TI - Studies of an antiendotoxin antibody in preventing the physiologic changes of endotoxemia in awake sheep. AB - In sheep, endotoxin (LPS) causes pulmonary hypertension, hypoxemia, leukopenia, exudation of protein-rich lung lymph, reduced dynamic compliance (Cdyn), and increased resistance to airflow (RL), changes similar to those seen in human sepsis and sepsis-induced ARDS. We used well-described methods in the awake sheep endotoxin model to evaluate the effectiveness of a commercially manufactured antibody to prevent the physiologic changes of endotoxemia. In awake sheep with chronic lung lymph fistulas, we used a whole-body plethysmograph to measure Cdyn, RL, and FRC. Pulmonary artery, left atrial, and systemic arterial pressures were recorded continuously. Arterial blood gases (for calculating AaPO2), leukocyte counts, and lymph samples were collected every 30 min. Animals received a 30-min (2 mg/kg) infusion of antiendotoxin antibody 4 h before LPS (0.75 micrograms/kg) challenge (n = 4), or were given a mixture of LPS (0.75 micrograms/kg) and antibody (2 mg/kg) that had been incubated in vitro at 37 degrees C for 30 min before infusion (n = 6). A control group given only 2 mg/kg of antibody (n = 4) showed no change in any measured parameter, whereas control animals receiving LPS alone (n = 6) exhibited a typical endotoxin response. In all animals receiving endotoxin, Cdyn declined by approximately 50% within 30 to 60 min, and RL increased approximately sixfold over a similar time course. Accompanying the abnormalities in lung mechanics were pulmonary hypertension, leukopenia, and widening of the AaPO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221583 TI - Effect of recombinant hirudin, a specific inhibitor of thrombin, on endotoxin induced intravascular coagulation and acute lung injury in pigs. AB - We hypothesized that thrombin activation may play a prominent role in endotoxin induced secondary organ failure, such as acute lung injury. To test this hypothesis, we administered a thrombin-specific inhibitor, recombinant hirudin, in endotoxemic pigs. The pigs were anesthetized, mechanically ventilated, and prepared with Swan-Ganz and extravascular lung water (EVLW) catheters. A total of 18 randomly selected animals received a pretreatment of 1,000 U/kg of hirudin, followed by a continuous infusion over 6 h of 500 U/kg/h given simultaneously with the infusion of 10 micrograms/kg/h of Salmonella abortus equi endotoxin. Another 18 animals received a continuous infusion over 6 h of endotoxin but did not receive hirudin. All animals were fluid resuscitated with 17 ml/kg/h of saline for the duration of the experiment. Data are expressed as the mean (95% confidence interval). Hirudin reduced the endotoxin-induced consumption of plasma fibrinogen from -110 (-138 to -82) mg/100 ml to -39 (-67 to -12) mg/100 ml (p = 0.0001) and endotoxin-induced increases in the soluble fibrin in plasma from 434 (369 to 499) ng/ml to 236 (171 to 300) ng/ml (p = 0.0002). These data suggest an effective inhibition of the endotoxin-generated thrombin by hirudin. Furthermore, hirudin significantly reduced endotoxin-induced increases in pulmonary vascular resistance from 32 (27 to 37) kdyn x s x cm-5 x kg to 20 (15 to 25) kdyn x s x cm 5 x kg (p = 0.0015) and increases in EVLW from 15.4 (13.2 to 17.6) ml/kg to 12.2 (10.0 to 14.4) ml/kg (p = 0.0299).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221584 TI - Doppler assessment of pulmonary hypertension induced by hypoxic breathing in subjects susceptible to high altitude pulmonary edema. AB - To verify the abnormal pulmonary vascular response implicated in the pathogenesis of high altitude pulmonary edema (HAPE), we examined the hemodynamic responses to hypoxia in HAPE-susceptible subjects (HAPE-S) by means of both right heart catheterization and pulsed Doppler echocardiography. The HAPE-S were seven men and one woman with a history of HAPE. Six healthy volunteers who had repeated experiences of mountain climbing without any history of altitude-related problems served as control subjects. The HAPE-S showed much greater increase in pulmonary vascular resistance (PVR) than did the control subjects, resulting in a much higher level of pulmonary arterial pressure (Ppa) under acute hypoxia both of 15% O2 and 10% O2. We then evaluated the usefulness of pulsed Doppler echocardiography in the prediction of pulmonary hypertension. Acceleration time (AcT) and right ventricular ejection time (RVET) were measured from the flow velocity pattern in the right ventricular outflow tract. The ratio of AcT to RVET was correlated to invasively determined mean Ppa (Ppa) and PVR. The results were as follows: (1) AcT/RVET = 0.52 to 0.0047 (Ppa), r = -0.93, SEE = 0.017, p less than 0.001 (HAPE-S); (2) AcT/RVET = 0.55 to 0.0055 (Ppa), r = -0.70, SEE = 0.030, p less than 0.001 (HAPE-S); (4) AcT/RVET = 0.52 to 0.00077 (PVR), r = -0.91, SEE = 0.016, p less than 0.001 (control subjects). We conclude that HAPE-S have a constitutional abnormality in the pulmonary vascular response to hypoxia, which is a possible causative factor of HAPE, and that pulsed Doppler echocardiography may be supportive to assess the pulmonary vascular pressor response in the HAPE S. PMID- 2221585 TI - Role of molecular diffusion in conventional and high frequency ventilation. AB - The influence of molecular diffusion on gas-mixing during conventional mechanical ventilation (CMV) and high frequency ventilation (HFV) was studied by observing the wash-in of six poorly soluble, inert gases in arterial blood. Anesthetized dogs were ventilated either with CMV or HFV. Following a step change in inspired gas composition, the increase in arterial concentrations of hydrogen, helium, methane, ethane, isobutane, and sulfur hexafluoride was determined by gas chromatography. The relative gas diffusivities encompassed a range of almost one order of magnitude. Propane, present in inspired gas during both the control and wash-in phases, served as an internal reference for calculation of blood tracer concentrations. The wash-in of all six inert gases followed a single exponential time course during both CMV and HFV. The rate of wash-in of each gas decreased with increasing molecular weight (MW). The relationship of rate constants to a measure of relative diffusivity (MW-0.5) was significantly different than zero for both types of ventilation. The slope of this relationship was three times larger for CMV than HFV, indicating that molecular diffusion has a greater role in gas mixing during ventilation with large tidal volumes. Diffusion has a minor role in gas mixing during high frequency ventilation with small tidal volumes. Demonstration of the presence of gas separation secondary to molecular diffusion during HFV is enhanced by measuring wash-in, rather than wash-out, of inert gases because gas separation is likely to be obscured as exhaled gases pass through the well-mixed central airways during gas wash-out. PMID- 2221586 TI - Endogenous opioids modulate the increase in ventilatory output and dyspnea during severe acute bronchoconstriction. AB - The aim of this study was to evaluate whether endogenous opioids are involved in the regulation of breathing pattern and respiratory drive during bronchoconstriction induced by methacholine (MCh). We studied six male asymptomatic asthmatics 18 to 35 yr of age. In a preliminary study we determined the concentration of MCh causing a 60% fall in FEV1 (PC60 FEV1). On two subsequent days, we measured breathing pattern, dyspnea sensation (Borg scale), mouth occlusion pressure (P0.1), and FEV1 before and 10 min after an intravenous injection of either naloxone (0.1 mg/kg) or saline according to a randomized double-blind crossover design. A MCh concentration equal to the PC60 FEV1 was then inhaled, and measurements were repeated 5 min later. Neither placebo nor naloxone affected baseline breathing pattern, P0.1, and FEV1. Naloxone pretreatment did not influence airway response to MCh; the mean percent fall in FEV1 was 65.9 +/- 1.3 and 64.7 +/- 1.2% (mean +/- 1 SE) on the placebo day and the naloxone day, respectively. After MCh inhalation no significant changes in VE, VT, and breathing frequency occurred when patients received placebo. However, P0.1 increased from 1.48 +/- 0.17 to 3.43 +/- 0.70 cm H2O (p less than 0.05), and VT/TI fell from 0.66 +/- 0.08 to 0.52 +/- 0.04 L/s (p less than 0.05). Naloxone pretreatment resulted in an increase in breathing frequency (from 18.2 +/- 1.7 to 22.8 +/- 2.6 breaths/min; p less than 0.05) and VT/TI (from 0.58 +/- 0.06 to 0.74 +/- 0.05 L/s; p less than 0.05) after MCh.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221588 TI - Effects of deep inhalation during early and late asthmatic reactions to allergen. AB - Eighteen asthmatic patients with a biphasic asthmatic reaction to house dust mite were studied. The effect of deep inhalation (DI) was quantitated by comparing the maximal expiratory flow at 40% (MEF40) of vital capacity from partial (P) and maximal (M) flow-volume curves, and specific airway conductance (SGaw) before and after DI (SGawDI). At baseline, the ratio MEF40M/P was significantly larger than unity (1.45 +/- 0.26 SD), whereas the ratio SGawDI/SGaw was not significantly different from unity (0.92 +/- 0.24). During early phase reaction, both MEF40M/P and SGawDI/SGaw were significantly increased to 2.66 +/- 0.97 and 1.96 +/- 0.47, respectively. During late phase reaction, when the FEV1 values were similar to those observed during early phase reaction, MEF40M/P and SGawDI/SGaw were 1.86 +/ 0.46 and 1.43 +/- 0.29, respectively, significantly higher than the values at baseline but significantly lower than those during early phase reaction. Similar results were obtained in a subgroup of nine patients when SGaw values during the late phase reaction were similar to those during the early phase reaction. We conclude that DI has a different effect during early and late asthmatic reactions, suggesting a different ratio of airway to parenchymal hysteresis. This may result from an increased parenchymal hysteresis (more peripherally located bronchial obstruction) or a decreased airway hysteresis (prominent airway inflammation) during the late phase reaction. PMID- 2221587 TI - Indomethacin does not inhibit the ozone-induced increase in bronchial responsiveness in human subjects. AB - Exposure of human subjects to sufficiently high levels of ozone can result in reversible changes in lung function (restrictive in nature) and increases in nonspecific airway responsiveness. Several studies have implicated products of cyclooxygenase metabolism in the mediation of these changes. The purpose of this study was to determine if indomethacin (a cyclooxygenase inhibitor) would alter the changes in the ozone-induced increase in responsiveness to methacholine or the ozone-induced decrease in lung function. Thirteen male subjects underwent three randomly assigned 2-h exposure to 0.4 ppm ozone with alternating 15-min periods of rest and exercise on a cycle ergometer (30 L/min/m2, body surface area). For the 4 days before each of the exposures, the subjects received either indomethacin (150 mg/day) or placebo, or no modification. Of the 13 subjects, only seven had both detectable indomethacin serum levels on the indomethacin Study Day and a significant increase in bronchial responsiveness to methacholine on the No Medication Day. For this group of seven subjects, we found that indomethacin did not alter the ozone-induced increase in bronchial responsiveness to methacholine (decrease in PC100SRaw for the different study days: no medication, -78.4 +/- 5.3% [mean +/- SEM]; placebo, -48.9 +/- 12.2%; indomethacin, -64.5 +/- 6.3%; p greater than 0.2), although indomethacin did attenuate the ozone-induced decrease in lung function. The decrease in the FEV1 for the different study days was as follows: no medication, -20.7 +/- 5.0% (mean +/- SEM); placebo, -19.2 +/- 6.3%; indomethacin, -4.8 +/- 3.7% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221589 TI - The effect of repetitive exercise on airway temperatures. AB - To determine if a relationship exists between intra-airway thermal events and the reduction in pulmonary mechanics that occur in asthmatics when they perform repetitive exercise, we recorded intrathoracic airstream temperatures in seven subjects during and after two identical bouts of cycle ergometry performed 30 min apart. From these data, global and regional thermal energy exchanges were calculated. Inspired air conditions, work loads, and minute ventilations were held constant for both trials. Pulmonary mechanics were measured prior to and serially after each challenge. As expected, the second provocation produced a smaller response than did the first. In association with these mechanical changes, the second challenge also produced less airway cooling and slower rewarming in the central airways. Hence, repetitive exercise trials performed over short intervals attenuate the essential thermal gradients necessary to produce obstruction. To the extent that these differences in intra-airway temperature reflect changes in perfusion, our data raise the possibility that the responsivity of the bronchial microcirculation of asthmatics may be altered by repetitive exercise. PMID- 2221590 TI - Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. AB - Several short-term studies have shown that inhaled steroids can reduce airway hyper-responsiveness in asthma. To evaluate whether prolonged treatment can bring about full recovery, this double-blind, randomized, controlled trial examined the effect of budesonide, 400 micrograms daily for 1 yr, on airway hyperresponsiveness. The time course and characteristics of improvements and associated changes in clinical asthma severity were also evaluated. Thirty-two stable adult asthmatics, requiring bronchodilators alone, were selected. Before and monthly throughout the study, airway responsiveness to methacholine was measured and clinical asthma severity assessed by questionnaire, daily bronchodilator use, and number of asthma exacerbations. Patients receiving budesonide showed a fourfold mean improvement in airway responsiveness compared with those receiving placebo (p less than 0.0005), whose responsiveness remained very stable. Fifteen of the 16 budesonide subjects improved and 5 returned to the normal range. Largest improvements occurred during the first 3 months but, in some, were still progressing slowly at 1 yr. Improvements in responsiveness were accompanied by significant improvements in asthma symptoms, bronchodilator use, and number of asthma exacerbations. The results show that regular, prolonged use of inhaled steroid can produce marked improvements in airway hyperresponsiveness, sometimes with full resolution, and these improvements are accompanied by clinically significant improvements in clinical asthma. PMID- 2221592 TI - Selective IgG subclass deficiencies and antibody responses to pneumococcal capsular polysaccharide antigen in adult community-acquired pneumonia. AB - We measured the serum concentrations of IgG subclasses in healthy subjects (n = 26) and in patients with community-acquired pneumonia (CAP) on admission (n = 38), at recovery (n = 21), and 9 months after admission (n = 19). Then, in 8 of the control subjects and 15 of the patients, we measured IgG subclasses and mean serum antibody concentrations of pneumococcal capsular polysaccharides before and 3 wk after immunization with a pneumococcal vaccine. Compared to the control subjects, the serum concentration of the IgG2 subclass was lower at admission in patients with CAP of bacterial or unknown cause (p less than 0.005). Concentrations of IgG subclasses in patients did not differ between admission and recovery, or between admission and 9 months later. After vaccination, in both control subjects and patients, there was an increase in the concentrations of IgG2 subclasses (p = 0.01) and antipneumococcal antibodies (p less than 10(-4)). We show that serum IgG2 concentration in patients with CAP of bacterial or unknown cause is lower than in healthy subjects and remains lower for several months. After immunization with a pneumococcal vaccine, the increase in serum concentrations of IgG subclasses and antipneumococcal antibodies in patients does not differ from those in control subjects. PMID- 2221591 TI - The relationship between respiratory impairment and asbestos-related pleural abnormality in an active work force. AB - With the general improvement in environmental controls in workplaces where asbestos is used, an increasing number of workers are seen who exhibit isolated pleural plaques. The question as to whether these are associated with respiratory impairment independently of parenchymal disease remains unresolved. The question was reinvestigated using quantitative gallium-67 lung scanning to take into account early parenchymal change not evident on the chest radiograph. We carried out a cross-sectional study of 110 construction insulators all currently at work. Overall, 58.2% had pleural abnormality, 52.5% pleural plaques only, and 5.5% diffuse pleural thickening as assessed from the PA chest radiograph. Compared with those without, those with any pleural abnormality had a decrease in FEV1 and FVC on average of 222 and 402 ml (p less than 0.05), and those with isolated pleural plaques, a decrease on average of 200 and 350 ml (p less than 0.05), after taking into account age, height, smoking status, and the presence of parenchymal abnormality as assessed by chest radiography and gallium uptake. The complaint of dyspnea with strenuous activities was also significantly related to the width and extent of chest wall pleural thickening (p less than 0.05), independently of parenchymal disease. This study suggests that the most common radiographic findings in asbestos-exposed, isolated pleural plaques are associated with a significant reduction in FEV1 and FVC, which cannot be attributed to the presence of radiographic and subradiographic pulmonary fibrosis. PMID- 2221593 TI - Epidemiology of infection by nontuberculous mycobacteria IX. Evidence for two DNA homology groups among small plasmids in Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum. AB - A 12.9 kb plasmid, pVT2, from a clinical Mycobacterium avium isolate, MD1, was cloned and radiolabeled for use as a DNA probe to examine the relatedness of plasmids in M. avium complex. That probe hybridized with plasmids isolated from M. avium complex strains from the environment (7 of 16) and from non-acquired immunodeficiency syndrome (AIDS) (10 of 17) and AIDS (5 of 6) clinical isolates. The similarity of plasmids from the environment with those from patients supports the hypothesis that the environment is a source of human M. avium complex infection. More striking was the observation that pVT2 hybridized with every plasmid (13 of 13 clinical and 5 of 5 environmental isolates) of 13.5 kb or smaller. A second probe, consisting of a 15.3 kb plasmid (pLR7) from another clinical isolate of the M. avium complex, hybridized with plasmids of 15.3 to 25 kb from environmental and clinical (AIDS and non-AIDS) isolates. There was no hybridization between pVT2 and pLR7. Thus, these two probes define two different groups of small mycobacterial plasmids. PMID- 2221594 TI - Quantitation of mast cells and eosinophils in the bronchial mucosa of symptomatic atopic asthmatics and healthy control subjects using immunohistochemistry. AB - We have used fiberoptic bronchoscopy to obtain endobronchial biopsies in which mast cells and eosinophils were enumerated using monoclonal antibodies directed against mast cell tryptase (AA1) and the eosinophil cationic protein (EG2). Eleven symptomatic atopic asthmatics treated with beta 2-agonists alone and six normal subjects were studied. Over a period of 2 wk prior to bronchoscopy, patients recorded asthma symptom scores, bronchodilator usage, and twice-daily peak expiratory flow. Five days before bronchoscopy, methacholine responsiveness was assessed. Two biopsies were taken from the subcarinae, one of which was processed into araldite for immunostaining by the streptavidin biotin immunoperoxidase method and the other into Spurr resin for electron microscopy. The number of AA1 staining mast cells present in the bronchial mucosa was not significantly different in the epithelium or submucosa between the asthmatic and the normal subjects. However, in the biopsies from asthmatics, there were significantly greater numbers of EG2-staining eosinophils in the epithelium (median, 1.2/mm versus zero; p less than 0.005) and in the submucosa (median, 50/mm2 versus 1/mm2; p less than 0.001). Electron microscopy showed morphologic features of mast cell and eosinophil degranulation in the asthmatics. No correlation could be established between mast cell or eosinophil numbers and indices of disease activity of PC20 methacholine, which points to the complexity of mechanisms responsible for the symptoms and the airway hyperresponsiveness of asthma. PMID- 2221595 TI - Timing of corticosteroid treatment. Effect of lung lymph dynamics in air injury in awake sheep. AB - In paired experiments, we studied the effects of high-dose methylprednisolone on the acute pulmonary injury caused by 4 h of venous air embolization in 19 chronically instrumented, unanesthetized sheep with lung lymph fistulas. We compared the effect of methylprednisolone (30 mg/kg intravenous bolus) given before embolization, early (1 H) in the course of embolization, late (3 h) in the course of embolization, or after embolization (at the beginning of the recovery period). We measured pulmonary hemodynamics and lymph dynamics. In six sheep we also fixed lung tissue for semiquantitative histology, and in some we measured leukocyte concentrations in blood and in pulmonary lymph. Methylprednisolone did not significantly affect pulmonary hemodynamics but it largely prevented lung injury when it was given before embolization. It also lessened the degree of lung injury when it was given during embolization, although this effect became less marked as treatment was delayed. Methylprednisolone had no effect on lung injury when given after embolization was completed (4 h). We found fewer leukocytes attached to air emboli and fewer endothelial cell gaps in the lungs of sheep given methylprednisolone as prophylaxis. Leukocyte counts were lower in lung lymph and higher in the circulating blood of methylprednisolone-treated sheep. We conclude that methylprednisolone has a preventive effect on air embolism lung injury, such that its effect is greater when given earlier during the development of injury. PMID- 2221596 TI - Sarcoidosis complicated by HIV infection: three case reports and a review of the literature. AB - We report three cases of sarcoidosis complicated by human immunodeficiency virus (HIV) infection and review four other isolated case reports in the literature. There is clinical overlap of both diseases, including symptoms, pulmonary function abnormalities, and lymphocyte function. Bronchoalveolar lavage (BAL) in these patients showed a lymphocytic alveolitis without pathogens. BAL lymphocyte subset analysis showed markedly depressed CD4+/CD8+ ratios in three patients. These data were clinically useful for distinguishing the CD8+ alveolitis associated with HIV infection from the CD4+ alveolitis associated with sarcoidosis. Three patients improved with corticosteroid therapy. Two patients with BAL-documented CD8+ alveolitis tolerated discontinuation of steroids. One patient's sarcoidosis improved without therapy concurrent with the diagnosis of Kaposi's sarcoma. Another patient developed sarcoidosis 1 yr after manifesting HIV positive serology. BAL can be used to distinguish the lymphocytic alveolitis of sarcoidosis from that associated with HIV infection. Patients with active sarcoidosis complicated by HIV infection can be effectively treated with corticosteroid therapy. PMID- 2221597 TI - Ciliary motility in two patients with yellow nail syndrome and recurrent sinopulmonary infections. AB - The yellow nail syndrome (YNS) is described as a combination of yellow nails, chronic lymphedema, pleural effusions, and recurrent sinopulmonary infections, but all these features need not be present for the diagnosis. The mechanism that renders patients with this syndrome susceptible to respiratory infections is not known. To determine whether abnormal ciliary motility is a predisposing factor, in vitro ciliary beat frequency (CBF) was measured in two patients with YNS and recurrent respiratory infections. In each case, the CBF was within normal limits (12 Hz). These data suggest that abnormal ciliary motility is not a pathophysiologic mechanism of recurrent sinopulmonary infections in YNS. PMID- 2221598 TI - Manual ventilation bags as a source for bacterial colonization of intubated patients. AB - A group of 14 intensive care unit (ICU) patients were studied to determine if manual ventilation bags (MVB) could serve as a source of bacterial or fungal pathogens that could colonize the respiratory tract of intubated patients. A total of 51 cultures were simultaneously obtained of patient's sputum, the exterior MVB surface, MVB port, and MVB interior (postexhalation valve). Pathogens colonizing or infecting the respiratory tract of intubated ICU patients were frequently simultaneously present on the exterior surface of the MVB and inside the MVB port used to connect the MVB with the endotracheal tube. In addition, coagulase-negative staphylococci and yeast were frequently present on the exterior surface of the MVB. The interior of the MVB was usually sterile. In three instances pathogens were isolated from the MVB before isolation from the patient's sputum. MVB may serve as a source for colonizing the respiratory tract of intubated ICU patients and/or the hands of medical personnel. The exterior surface and port of MVB should be cleaned of visible debris and disinfected at least once a day. PMID- 2221599 TI - NHLBI Workshop Summary. Effect of physical forces on lung structure, function, and metabolism. PMID- 2221601 TI - Training programs in adult respiratory disease and training programs in pediatric respiratory disease. PMID- 2221600 TI - Environmental Controls and Lung Disease. PMID- 2221602 TI - Relation between tumor necrosis factor-alpha and granulocyte elastase-alpha 1 proteinase inhibitor complexes in the plasma of patients with cystic fibrosis. PMID- 2221604 TI - Management of the acute abdomen complicating oral anticoagulation therapy. AB - Acute abdominal pain in the patient receiving oral anticoagulants poses a difficult diagnostic and therapeutic challenge. We describe two cases of peritonitis requiring laparotomy in anticoagulated patients, and review 49 similar case reports from the world literature. These patients were usually explored for signs of bowel obstruction. At operation, the intestine often appeared infarcted, but pathologic examination commonly revealed intramural hematomata. In contrast, we present microscopic evidence of hemorrhagic cecal infarction complicating oral anticoagulation therapy in one patient. Intramural intestinal hemorrhage is the most common cause of acute abdominal pain in the anticoagulated patient who undergoes laparotomy. In addition to intramural hemorrhage, 14 per cent of patients had coexistent volvulus, appendicitis, intestinal wall disruption or intestinal infarction. We conclude that anticoagulated patients with suspected intramural intestinal hemorrhage may have severe intraabdominal pathology requiring operation. Therefore, operation is mandatory for patients who fail to improve after a short course of expectant management. PMID- 2221603 TI - A prospective assessment of the Garren-Edwards Gastric Bubble and bariatric surgery in the treatment of morbid obesity. AB - Morbid obesity is a serious medical hazard, and effective alternatives to surgery have been unsuccessful. In 1985, the Garren-Edwards Gastric Bubble (GEGB) was offered as an adjunct to dietary and behavioral therapy for weight loss treatment. The safety and efficacy of the GEGB were compared with bariatric surgery, the current standard for the treatment of morbid obesity. Fifty-seven patients received GEGB and 77 underwent bariatric surgery. GEGB patients were divided into two groups: those who attended group therapy and those who did not. This study showed that bariatric surgery was far more effective in reducing excess body weight during a 12-month period compared with the GEGB plus group therapy and the GEGB alone. The morbidity from bariatric surgery was greater than in the GEGB-treated groups, while the cost for uncomplicated cases for a year's treatment was comparable. It is concluded that the GEGB does not offer an effective alternative to bariatric surgery in the treatment of morbid obesity. PMID- 2221605 TI - Nonoperative management of small-bowel obstruction with endoscopic long intestinal tube placement. AB - Intestinal obstruction remains a major cause of morbidity and mortality in surgical patients. We reviewed the records of 77 patients with mechanical small bowel obstruction who were treated with endoscopically and fluoroscopically placed Leonard long intestinal tube decompression. Most patients (59%) had failed a trial of nasogastric tube or Miller-Abbott tube decompression. Overall, 29 per cent of patients were able to resolve their obstruction with Leonard tube decompression alone. Subdivision of patients on the basis of the etiology of their obstruction demonstrated a much higher rate of success for tube decompression in adhesive obstruction (37%) versus malignant obstruction (12%) or inflammatory obstruction (no successes). Patients with radiographic and clinical evidence of complete intestinal obstruction were significantly less likely to respond to long intestinal tube treatment (13%). The long intestinal tube was easily passed in all patients. There were no complications of the intubation procedure in our series, and the incidence of tube-related complications was four per cent. We conclude that an initial period of long intestinal tube decompression allows a significant percentage of patients with mechanical small bowel obstruction to be treated nonoperatively, particularly if a partial obstruction from postoperative adhesions is present. Patients who have failed a trial of nasogastric tube decompression and are poor operative risks should also be considered for long intestinal tube placement. PMID- 2221606 TI - The influence of sclerotherapy on gastric mucosal blood flow distribution. AB - Hemodynamic events and structural vascular changes of the gastric mucosa in cirrhotics have caught the attention of investigators in the recent past, but as yet it is not known whether therapeutic interruption of variceal blood flow at gastroesophageal level alters such portal hypertensive mucosal features. The newly developed endoscopic laser-Doppler technique was used to assess whether variceal eradication by means of endoscopic sclerotherapy influences the gastric mucosal congestion in portal hypertension patients. Gastric mucosal blood flow was determined at ten defined sites of the stomach, before the first session of sclerotherapy and after complete variceal eradication had been achieved in 15 patients. A statistically significant decrease (P less than 0.01 to 0.05) in microcirculation was found at the gastric antrum and corpus, an increase at the pylorus (P less than 0.05), but no change in the fundic area. An important question following these findings is: What are the consequences of such aggravation of gastric congestion on the integrity of the gastric mucosa? PMID- 2221607 TI - A five-year U.S. Army experience with 36,250 abdominal hernia repairs. AB - Thirty-six thousand two hundred fifty abdominal hernia repairs were performed in U.S. Army medical treatment facilities during a five-year period. This study presents data about the type of hernia, incidence of complications by obstruction or strangulation, age, sex, and mortality. Hernias occurring with intestinal obstruction or gangrene (strangulation) are referred to as complicated hernias. Inguinal hernias in children less than two years of age, femoral hernias, and unusual (such as internal or obturator) hernias were found to have an increased incidence of complications. Surgical repair of ventral, umbilical, and femoral hernias was done with a low surgical risk and the presence of complications did not significantly increase this risk. An increased risk of mortality is associated with the repair of complicated unusual hernias and complicated inguinal hernias in patients more than 60 years of age. PMID- 2221608 TI - Spontaneous splenic rupture following infectious mononucleosis. AB - Four cases of spontaneous splenic rupture after infectious mononucleosis (IM) have been treated at this institution since 1978. The condition is rare, occurring in 0.1-0.5 per cent of patients with proven infectious mononucleosis. Splenectomy is considered the treatment of choice for these patients. However, because recent trends in the management of traumatic splenic rupture are moving towards nonoperative treatment with selected patients, a similar approach has been considered for the patient with spontaneous splenic rupture following IM. The major reason for avoiding splenectomy is the increased incidence of sepsis in splenectomized patients. Yet, splenic rupture is accompanied by hemorrhage and the risks associated with blood transfusion for ongoing hemorrhage are of similar magnitude as those of sepsis following splenectomy. In addition, the grossly abnormal spleens seen at operation tend to include large, contained hematomas that may also be prone to rupture. Therefore, operative management still appears to be the preferred treatment for spontaneous splenic rupture following IM. Splenectomy is curative, safe, and obviates the need for transfusion, extended hospitalization, and activity restriction. PMID- 2221609 TI - Comparison of ulcer surgery at a Veterans Administration and University Hospital. AB - We compared the patient populations and outcome of surgery for peptic ulcer disease in 81 patients at a Veterans Administration Hospital (OVAH) and 97 patients at an affiliated University Hospital (UNH). The surgeons and choice of operation were comparable at both facilities. Patients were similar with respect to severity of ulcer disease, percentage of elderly patients and distribution of comorbid conditions. There were significantly more female patients (45% vs 2%, P less than 0.05), patients less than 40 years old (22% vs 6%, P less than 0.05), and patients with gastric ulcers (27% vs 12%, P less than 0.05) at UNH. Alcoholism was more prevalent at OVAH (57% vs 22%, P less than 0.05). Postoperative morbidity and mortality rates were 27 per cent and 14 per cent at OVAH and 25 per cent and 16 per cent at UNH. These data suggest that quality of care for surgical therapy of ulcer disease at a VA Hospital is comparable to its tertiary care affiliate with a similar patient population. PMID- 2221610 TI - Toxic shock syndrome after inguinal hernia repair. Report of a case with patient survival. AB - A 40-year-old man developed fulminant multisystem failure several days after elective repair of an inguinal hernia. Toxic shock syndrome (TSS) was diagnosed. There was, however, no evidence of wound infection at the time of multisystem failure. Only later in his hospital course did the wound drain. Staphylococcus aureus was cultured from the wound and was the presumed etiologic agent in the patient's life-threatening illness. The patient recovered fully with supportive care, antibiotics, and surgical debridement of the inguinal hernia site. This case is discussed in the context of existing literature on the toxic shock syndrome. The site of infection is typically nonsuppurative, but the systemic manifestations are typically life threatening. The responsible organism is commonly believed to be a strain of S. aureus that expresses a toxin (TSS toxin 1) that effects multisystem failure, but which also diminishes the local inflammatory response and explains the benign appearance of the wound. Although this is a rare clinical entity, elective surgical procedures complicated by fatal TSS have been reported. Surgeons should understand this disease and the management necessary to avert mortality. PMID- 2221611 TI - Ceftazidime/clindamycin versus tobramycin/clindamycin in the treatment of intra abdominal infections. AB - In order to assess the efficacy and toxicity of ceftazidime as a substitute for aminoglycosides in the treatment of intra-abdominal sepsis, a prospective randomized trial was conducted. Ninety-four patients (49% trauma) were randomized to receive ceftazidime/clindamycin (CAZ/C) (n = 47) or tobramycin/clindamycin (T/C) (n = 47). CAZ (2.0 gm) and C (0.9 gm) were administered intravenously every 8 hours while T dosage was adjusted to maintain peak (5-8 mg/L) and trough (less than 2 mg/L) concentrations. Age, sex, baseline serum creatinine, and etiology of infection were comparable in the two groups. Clinical cure was similar in culture positive and culture-negative patients who received CAZ/C (94% vs 88%). The clinical cure rate however was significantly lower in the T/C culture positive (73%) than in the culture negative patients (100%) (P = 0.016). Pathogenic organisms were eradicated in 100% (30/30) and 76% (13/17) of CAZ/C and T/C patients, respectively (P = 0.0006). Nephrotoxicity Nephrotoxicity or ototoxicity was observed in none of the CAZ/C patients and in one and two T/C patients, respectively. CAZ/C more effectively eradicated the bacteria isolated from these patients and no significant difference in clinical response was observed in culture-positive patients. These findings plus the lack of toxicity suggest that CAZ/C is an effective alternative for treatment of IAI. PMID- 2221612 TI - A comparison of parallel versus perpendicular placement of retention sutures in abdominal wound closure. AB - A new technique for placement of retention sutures is described. Twenty-five rats underwent midline laparotomy incision. The control group was closed with traditional placement of through-and-through retention sutures placed in a perpendicular direction to the wound. The experimental group was closed with retention sutures placed in a parallel direction to the wound as described below. Wound bursting strength was significantly (P less than 0.001) greater at one to five days in the experimental group compared with the control animals. In addition, inflammatory reaction and pressure necrosis were greater in the control group. It appears that parallel placement of sutures has less of a tendency to cut through tissue when subjected to the distracting forces on a midline wound. PMID- 2221613 TI - Urgent management of a giant scrotal hernia. AB - An unusual case of giant scrotal hernia is presented. Hernias of this magnitude are extremely rare, even in underdeveloped countries, and their repair is challenging to the surgeon and stressful to the patient. Only a few case reports on the use of pneumoperitoneum prior to herniorrhaphy have been published; however, our patient's accompanying complications of diabetes mellitus and gastrointestinal symptoms precluded the use of pneumoperitoneum. The emergency management, including the expansion of the abdominal cavity with prosthesis, the ensuing postoperative complications, and the patient outcome, are discussed. PMID- 2221614 TI - CT diagnosis of acquired small bowel volvulus. AB - Small-bowel volvulus is an uncommon but important cause of small-bowel obstruction and often results in ischemia or infarction. Clinical examination and plain film radiography may be nondiagnostic, leading to delay in surgical intervention with subsequent increase in morbidity and mortality. We present two patients in whom the diagnosis of strangulating small-bowel volvulus was made by computed tomography (CT), allowing rapid surgical correction of this potentially life-threatening condition. PMID- 2221615 TI - Biomechanical performance of cardiovascular needles. AB - Standardized reproducible tests have been developed to determine the biomechanical performance of cardiovascular needles. The parameters used to assess performance were sharpness, resistance to bending, and ductility. Three comparable groups of taper point cardiovascular needles were selected from different manufacturers for these biomechanical studies. The results of this testing demonstrated that needle geometry, needle composition, and the manufacturer were important determinants of needle performance. When needles of comparable size were evaluated, the biomechanical performance of cardiovascular needles manufactured by Ethicon, Inc., were superior to needles produced by other manufacturers. The superior performance characteristics of the cardiovascular needles produced by Ethicon, Inc., were related to their unique stainless steel alloy, American Society for Testing Materials 45500, which has greater yield and tensile strengths than the alloy used by the other manufacturers. Scanning electron microscopic photographs of the Ethicon, Inc., needle revealed a uniform taper point geometry without irregularities. The deformations of the points of cardiovascular needles produced by the other manufacturers could alter their performance. PMID- 2221616 TI - Lung lobe torsion following lobectomy. AB - Three cases of postoperative pulmonary lobe torsion were reported. Two of three showed hemorrhagic infarctions, and as a result underwent rethoracotomies and removal of the affected lobes. From these experiences, we consider that computed tomography (CT) and bronchofiberscopic examinations are useful for the diagnosis of advanced torsion. PMID- 2221617 TI - Metallurgically bonded needle holder jaws. A technique to enhance needle holding security without sutural damage. AB - A new needle holder jaw face has been specifically designed and developed to increase needle holding security without sutural damage. Tungsten carbide particles have been metallurgically bonded into the stainless steel jaw to create a fine granular surface. This bonded jaw enhances needle holding security by limiting either twisting or rotation of the clamped needle. In addition, compression of the monofilament synthetic sutures by the bonded jaws does not reduce suture breaking strength. PMID- 2221618 TI - Effects of method of hemostasis on wound-infection rate. AB - Adequate hemostasis is important in preventing postoperative wound infection. This study compared four methods of hemostasis: specific pinpoint vessel electrocautery (SPC), specific vessel ligation with 4-0 vicryl (SVL), nonspecific electrocautery of vessel plus excessive surrounding tissue (NSC), and nonspecific ligation of vessel and excessive surrounding tissue with 4-0 vicryl (NSL), on the rate of wound infection in rabbits that were contaminated with 10(6) Staphylococcus aureus. There was no statistical significant increase in the rate of wound sepsis when electrocautery was used in a fashion producing minimal nonviable tissue compared to specific vessel ligation. Electrocautery use for specific vessel hemostasis does not result in a higher wound infection rate in contaminated wounds. PMID- 2221619 TI - Penetrating injuries of the abdominal aorta. AB - The charts of 56 consecutive patients with penetrating injuries to the abdominal aorta were reviewed in an attempt to identify prognostic factors. Mechanism of injury was gunshot wound (GSW), 82 per cent (.22 cal: 15.2%; greater than .38 cal: 84.8%); shotgun wound (SGW), 5 per cent; and stab wound (SW), 13 per cent. Overall mortality was 73 per cent, with GSW 78 per cent (.22 cal: 0%; greater than .38 cal: 92%), 67 per cent with SGW, and 43 per cent with SW. Average initial systolic blood pressure (ISBP) was 53 (0-130); 87 (0-120) in survivors; and 40 (0-130) in nonsurvivors (NS). Eighteen patients (32%) had no ISBP, with one survivor. Thirty (54%) patients had ISBP less than 70, with three survivors. Six Emergency Department (ED) thoracotomies were performed, with five patients surviving to reach the operating room (OR), and none surviving long-term. Ten patients died in the ED, 18 during surgical intervention, six within 24 hr, and seven greater than 24 hr postop. Average time from injury to OR was 75 minutes, with 122 minutes in survivors, and 53 minutes in nonsurvivors (P less than 0.05); 49 minutes in those dying in the OR; and 58 minutes in those surviving the OR but dying postop (NS). At surgery, six patients had thoracotomy before celiotomy for control of the thoracic aorta, with three surviving the OR and two surviving long term. Survivors had 2.53 associated injuries; nonsurvivors had 2.89 (NS). No significant difference was noted in number or location of associated injuries between survivors and nonsurvivors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221620 TI - [Antiviral drugs in pediatrics]. PMID- 2221621 TI - [Exercise test in exercise-induced asthma in children: study of delayed response]. AB - In this study we perform the exercise broncho-provocation test according to a protocol and involving 27 children with allergic asthma to study the prevalence and distinctive traits of the late response in exercise-induced asthma (EIA). At the conclusion of the study, 20 patients (74%) were diagnosed of EIA through some of the tests employed (ergometric bicycle, free run). In the cases where both tests were negative, we reproduced in a controlled manner the exercise reported as asthmogenic on the basis of anamnesis; no positivity was observed for the test in any case. Prevalence of late asthmatic response was 40% (8/20); mean beginning time to this response was 4-6 hours, lasting less than 1 hour and with a mean intensity rate of 26.8% (measured as the percentage of PEFR drop according to the preexercise basal value). The results are discussed, comparing them with those of other authors and with the allergen provocation response pattern; in addition the methods used and therapeutic implications in view of the results are dealt with. PMID- 2221623 TI - [The form of crystallization of perspiration in pancreatic cystic fibrosis]. AB - The present study is based on the typical dendritic forms of the sweat crystallization from patients with cystic fibrosis (CF). The phenomenon was analyzed in sweat collected by pilocarpine iontophoresis in 26 affected subjects (Homozygotes), 42 heterozygotes and 100 healthy-control subjects. The positive crystallization pattern (dendritic form), became useful in identifying the affected patients in 100% of cases and in differentiating them from the healthy control subjects (100%, negative crystallization). The positive crystallization pattern was not altered by decreasing the electrolytes concentration in the sweat. This test could be a help to evaluate the diagnosis of cystic fibrosis. PMID- 2221622 TI - [Results of the treatment of gastroesophageal reflux and peptic esophagitis using cisapride]. AB - Cisapride is a new prokinetic agent that acts at gastric emptying, esophagic peristalsis and the pressure of the low esophagic sphincter. In the present study we grave Cisapride for 12 weeks to 34 patients with severe pathologic gastroesophageal reflux and/or peptic esophagitis. The results show an important improvement of the clinic, pH monitoring, endoscopic and histologic alterations. PMID- 2221624 TI - [Importance of childhood accidents. Results of a regional study]. AB - In order to know the importance and epidemiology of childhood accidents, a prospective study was made in a Spanish region, this study was founded in death certificates and 3,344 questionnaires from children under 7 years old, accidented in 1986 and attended in emergency departments in our region. The information was coded and analysed by computer of the Murcia University. Accidents are the main cause of death in children aged over 1 year, as a common cause of assistance in emergency departments. Its characteristic are common to most countries, but the authors find some differences in our region. It is necessary to dedicate bigger effort to study and prevention of childhood accidents. PMID- 2221625 TI - [Standardization of forced spirometry. Analysis of the basal pulmonary function (PEF, FEF2575, FEF50) in a selected group of children]. AB - This is a study of the ventilatory function (FEF2575, FEF50, PEF) by dry spirometer Vitalograph in 1,566 children of both sexes with ages ranging from 7 to 14 years; 1,156 children (73.6%) were selected as reference population. Height was the biometric parameter with the greatest correlation to the functional variables studied in both sexes, except to PEF in females. Significant differences were observed in functional variables between male and female subjects. Multiple and simple linear regression equations and percentiles tables for each sex are presented. PMID- 2221626 TI - [Basal pulmonary function studies (FVC, FEV) in a selected child population]. AB - This is a study of the ventilatory function (FVC, FEV1) by dry spirometer Vitalograph in 1566 children of both sexes with ages ranging from 7 to 14; 1156 children (73.6 per 100) were selected as reference population. Height was the biometric parameter with the greatest correlation to the functional variables studied in both sexes. Significant differences were observed in functional variables between male and female subjects. Multiple and simple linear prediction equations and percentiles tables for each sex are presented. The results of the present study are compared with those of previously published of children. PMID- 2221628 TI - [Staphylococcus coagulase negative infection in neonates caused by intravascular catheters. Prospective study]. AB - We present a prospective study about 100 intravascular catheters inserted into 88 newborns. 35 positive blood cultures were obtained; 19 with clinical signs of sepsis and 16 in asymptomatic newborns. Coagulase-negative Staphylococci were the most common isolated organisms -84.2% in the symptomatic cases, 100% in the asymptomatic ones. A comparative study was realized between cases of catheter related sepsis with positive blood culture of coagulase-negative Staphylococcus (n = 14) versus asymptomatic cases with positive blood culture (n = 16). Risk factors in the appearance of symptoms are: prematurity, newborns old age when catheters are inserted and days of catheter placement. PMID- 2221627 TI - [Anorexia nervosa in adolescents]. AB - We have made a revision of our casuistics, according DSM-III-R, between 1968 and 1988, of 53 cases. The ages go between 10 and 21 years, being the more frequent those from 13 to 15 years old. In the sample 5 males stand out. The most common symptomatology in the course of the disease was in its first phase: "prudent child", irritability or obsessions. In the second phase dominated phobias, obsessions, irritability, agitation and anxiety. And in the third phase we found more often: passiveness, inhibition, phobias and obsessions. As regards the treatment, individual psychotherapy was practised in 42 out of the 53 cases, with an evident improvement of personality. The environmental separation, circumstance we considered essential though not sufficient to cure the disease, was put in practice in 39 of the cases. And the biological treatment, generally through antidepressives, was administered to 44 patients, some of whom took more than one medication during the course of the treatment. The evolution was positive in 35 out of the 53 cases. Fifteen abandoned the treatment; and one suffered from a psychotic depression and the other two did not follow the recommended environmental separation. PMID- 2221629 TI - [Wolff-Parkinson-White syndrome: long-term follow up study in a pediatric population (86 cases)]. AB - Eighty six patients (48 males and 38 females) with W-P-W diagnosed before the age of 15 years had a maximum follow-up of 20 years. The mean age at diagnosis was 3 y and 5 m., most cases being concentrated in the first 6 months of life (37%). Twenty seven (31.4%) had associated heart disease, the more common being: ventricular septal defect (6 cases), Ebstein malformation (5 cases) and transposition of the great arteries (4 cases). Supraventricular tachycardia (SVT) was the commonest form of clinical presentation, followed by examination because heart murmur or heart disease. Fifty patients (58%) had SVT along the follow-up. SVT was more frequent in W-P-W type A than in type B (p less than 0.05). There was a statistically significant correlation (p less than 0.001) between the association of SVT and the absence of heart disease, but the finding must be questioned because the true incidence of W-P-W in normal population is unknown. There also were a significant correlation (p less than 0.05) between the association of W-P-W type B and the presence of heart disease. An electrophysiologic study was performed in 11 patients, 6 of them being concealed W-P-W. Four patients were operated upon because of SVT. We have studied a total of 154 SVT episodes in the 50 patients with SVT. The treatment more frequently used to finish the SVT included: verapamil, DC-Countershock and Digoxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221630 TI - [Neonatal cardiac insufficiency caused by a cerebral arteriovenous fistula. Review of the authors' cases]. AB - Four cases of newborn infants presenting congestive heart failure in the first two weeks of life with the clinical suspicion of cerebral arteriovenous fistula which was subsequently confirmed by cerebral echography or TAC and, after death, by necropsy, are described. Only one patient survived, the one treated surgically. CONCLUSION: It is necessary to carry out urgent diagnosis with an early surgical operation, the only possibility of survival for these children. PMID- 2221631 TI - [Primary pancreatic hydatid cyst and primordial familial dwarfism]. AB - A 10 years and 7 months old male, was studied for a pathologic, primordial hipogrowing disease, probably due to a recessive and autosomic transmission, because he has got a sister with the same illness, and he was diagnostified of a pancreatic cyst, whind was found in an echographical exploration and established by scanner as intraglandular cyst. There are no others cysts found detected in a complete body-check. The chirurgic findings was a solitary hydatidic intrapancreatic cyst whid was extirpated. The patient's and sister's facial characteristics (big nose, long and thin neck, large forehead), the normal hormonal study in this case, the observation of small bone defects (first finger of the foot thicker than usual, cone epifisis in hands), a normal intelligence and the not accordance between them and the usual in literature described kind, suggest to be a different form the congenital autosomic, recessive dwarfism, not according to the usual one. PMID- 2221632 TI - [Are we well informed about the health status of adolescents?]. PMID- 2221633 TI - [Splenic torsion in a patient with prune belly]. PMID- 2221634 TI - [Trans-sphenoidal encephalocele associated with hypopituitarism and arteriovenous malformations]. PMID- 2221635 TI - [Intervertebral calcification syndrome: clinical manifestation nine years after radiologic diagnosis]. PMID- 2221636 TI - [A case of childhood choreoathetosis induced by diphenylhydantoin]. PMID- 2221637 TI - [Ring chromosome 13 (type I) 45,XY,-13/46, XY,r(13)(p11:q34)]. PMID- 2221638 TI - [Population studies on childhood accidents]. PMID- 2221639 TI - [Benign acute myositis associated with respiratory syncytial virus infection]. PMID- 2221640 TI - [Robinia pseudoacacia poisoning]. PMID- 2221641 TI - [Chronic sulmetin papaverin poisoning]. PMID- 2221643 TI - Clinical practice guidelines. PMID- 2221642 TI - [Serological markers in active celiac disease]. PMID- 2221644 TI - Cassandra and the clinician: are clinical prediction rules changing the practice of medicine? PMID- 2221645 TI - Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. A randomized controlled study. AB - OBJECTIVE: To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 (calcitriol) in the treatment of osteoporosis. DESIGN: Two-year, double-blind, randomized clinical trial. SETTING: University medical center. PATIENTS: Fifty postmenopausal women with vertebral fractures recruited by referral. INTERVENTION: Calcium intake was adjusted to 25 mmol/d (1000 mg/d) at baseline. Patients were then randomized to treatment with either calcitriol or placebo. During the study, calcium intake was reduced to 15 mmol/d (600 mg/d) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L (less than 11.0 mg/dL) or urine calcium less than 9.96 mmol/d (less than 400 mg/d). MEASUREMENTS AND MAIN RESULTS: After 2 years, the mean dose of calcitriol in the treated group was 0.62 micrograms/d. Bone mineral density of the spine increased 1.94% with calcitriol therapy and decreased 3.92% with placebo (P = 0.001). Total body calcium increased 0.21% with calcitriol therapy and decreased 1.85% with placebo (P = 0.004). Patients receiving placebo had significant decreases in spine density (P = 0.0007) and total body calcium (P = 0.0004). There were no differences in vertebral fracture rates between the groups. Renal function studies were not statistically different between the groups after 2 years. CONCLUSION: The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium. No adverse effects on renal function were seen after long-term calcitriol therapy. PMID- 2221646 TI - Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. AB - OBJECTIVES: To determine the spectrum of clinical manifestations in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis; to determine renal and patient survival in these patients; to compare survival among patients treated with corticosteroids alone, corticosteroids plus intravenous cyclophosphamide or corticosteroids plus oral cyclophosphamide; and to assess the correlation of disease manifestations and treatment response with ANCA subtypes and serial autoantibody titers. DESIGN: Inception cohort study; mean follow-up of 24 months. SETTING: Collaborative network of 120 university and private practice nephrologists (The Glomerular Disease Collaborative Network). PARTICIPANTS: Seventy patients with ANCA and pauci-immune necrotizing and crescentic glomerulonephritis, of whom 59 were treated with either corticosteroids alone (14 patients), corticosteroids plus oral cyclophosphamide (30 patients), or corticosteroids plus intravenous cyclophosphamide (15 patients). MAIN RESULTS: Of the 70 patients, 18 had renal-limited disease (idiopathic crescentic glomerulonephritis); 15, nonpulmonary extrarenal disease consistent with polyarteritis nodosa; and 37, pulmonary disease consistent with Wegener granulomatosis or alveolar capillaritis. There were overlapping manifestations of disease between patients with autoantibodies producing a cytoplasmic pattern and patients with autoantibodies producing a perinuclear pattern; however, the perinuclear pattern occurred more frequently in patients with renal-limited disease. Renal and patient survival was 75% at 24 months, and no difference in survival was seen between patients with renal-limited disease and those with systemic disease. No differences in survival were seen between patients treated with oral cyclophosphamide and those treated with intravenous cyclophosphamide; however, the comparative data from patients treated with corticosteroids alone were inconclusive. In general, autoantibody titers correlated with response to treatment and disease activity, but there were exceptions. CONCLUSIONS: Patients with ANCA have various forms of necrotizing vascular inflammation, ranging from renal-limited disease to widespread systemic vasculitis, including polyarteritis nodosa and Wegener granulomatosis. Oral corticosteroids with either oral or intravenous cyclophosphamide appear to be equally effective therapy for ANCA associated glomerulonephritis. PMID- 2221647 TI - Clinical prediction rule for pulmonary infiltrates. AB - OBJECTIVE: To derive and validate a clinical rule for predicting pneumonic infiltrates in adult patients with acute respiratory illness. DESIGN: Prevalence studies in three settings. SETTING: Emergency departments of the University of Illinois Hospital at Chicago, the University of Nebraska Medical Center at Omaha, and the Medical College of Virginia at Richmond. PATIENTS: Symptoms, signs, comorbidity data, and chest roentgenogram results were recorded for 1134 patients from Illinois (the derivation set), 150 patients from Nebraska, and 152 patients from Virginia (the validation sets). All patients presented to the emergency department and had a chest roentgenogram to evaluate fever or respiratory complaints. MEASUREMENTS AND MAIN RESULTS: Within the training set, temperature greater than 37.8 degrees C, pulse greater than 100 beats/min, rales, decreased breath sounds, and the absence of asthma were identified as significant predictors of radiographically proved pneumonia in a stepwise logistic regression model (P = 0.001). The logistic rule discriminated patients with and without pneumonia in the training set with a receiver operating characteristic (ROC) area of 0.82. In the validation sets, the rule discriminated pneumonia and nonpneumonia with ROC areas of 0.82 and 0.76 after adjusting for differences in disease prevalence (P greater than 0.2 compared with the training set). The predicted probability of having pneumonia for patients with different clinical findings corresponded closely with the incidence of pneumonia among patients with such findings in the three settings. CONCLUSIONS: Among adults presenting with acute respiratory illness, a prediction rule based on clinical findings accurately discriminated patients with and without radiographic pneumonia, and was used in two other samples of patients without significant decrement in discriminatory ability. This rule can be used by physicians to develop more effective strategies for detecting pneumonia and for helping to determine the need for radiologic study among patients with acute respiratory disease. PMID- 2221648 TI - Regional deposition of aerosolized pentamidine. Effects of body position and breathing pattern. AB - OBJECTIVE: To evaluate the effects of varying body position and breathing pattern on overall lung distribution of aerosolized pentamidine. DESIGN: Nonrandomized control trial with four weekly inhalational treatments. SETTING: The nuclear medicine department of a voluntary hospital. PATIENTS: Sixteen men with the acquired immunodeficiency syndrome (AIDS) or positive serology for the human immunodeficiency virus (HIV). Thirteen patients (81%) completed the study. INTERVENTIONS: Patients inhaled a solution of either saline and technetium-99m bound to diethylenetriamine penta-acetic acid or sterile water, pentamidine (60 mg), and technetium-99m bound to human serum albumin. On weekly visits, the patients inhaled the aerosol solution using four methods: sitting, supine, sitting with an abdominal binder, and sitting and breathing from residual volume with a shallow inspiration. MEASUREMENTS AND MAIN RESULTS: Deposition scans, obtained after each aerosol inhalation, were superimposed on each patient's equilibrium xenon scan, and a frequency distribution histogram was constructed. An asymmetry index was determined from this histogram. The lower the asymmetry index, the more homogeneous the aerosol distribution. Only use of the supine position showed a significant decrease in the asymmetry index (mean, 0.34 +/- 0.02 in the supine position, 0.48 +/- 0.03 in the sitting position; P less than 0.001). CONCLUSIONS: Aerosol distribution in the lungs was more uniform when administered to patients in the supine position. Patients receiving aerosolized pentamidine may benefit from inhalation in the supine position; these results should be verified by clinical study. PMID- 2221650 TI - Efficacy of exercise thallium-201 scintigraphy in the diagnosis and prognosis of coronary artery disease. American College of Physicians. PMID- 2221649 TI - Exercise thallium-201 scintigraphy in the diagnosis and prognosis of coronary artery disease. AB - OBJECTIVE: To determine the discriminant accuracy of exercise thallium-201 myocardial perfusion scintigraphy for the diagnosis and prognosis of patients with known or suspected coronary artery disease. DATA IDENTIFICATION: A survey of the National Library of Medicine MEDLINE database. STUDY SELECTION: The key medical subject headings used were coronary disease, myocardial infarction, radionuclide imaging, and thallium. A total of 122 retrieved studies were considered relevant and were reviewed in depth. DATA EXTRACTION: Only studies reporting both the sensitivity and specificity of thallium scintigraphy were analyzed. RESULTS: Discriminant accuracy for diagnosis and prognosis was summarized in terms of pooled sensitivity and specificity. CONCLUSIONS: Exercise thallium scintigraphy is useful in the noninvasive diagnosis of coronary artery disease, especially in patients with abnormal resting electrocardiograms, restricted exercise tolerance, and intermediate probability of having disease at the time of testing as well as of defining the prognosis of patients with known or suspected coronary artery disease, especially in those with previous myocardial infarction. Because of various shortcomings in the published record, however, the marginal discriminant accuracy and cost effectiveness of thallium scintigraphy compared with conventional clinical assessment and exercise electrocardiography remain controversial. PMID- 2221651 TI - A long run for a short jump: understanding clinical guidelines. AB - Clinical guidelines for application of medical technologies are being advanced as consensus recommendations by consumer groups, professional societies, and health care managers. Although different groups' guidelines for use of a given technology may vary--or even conflict--depending on the methods by which they were formulated, their proponents' interests, and the subjective values attached to potential outcomes, they make it possible to quantify somewhat and predict, on a population basis, clinical gains relative to costs. Clinical guidelines can introduce into patient-physician decision making systematic consideration of a given technology's demonstrated efficacy and its likely advantages compared with its personal and its societal costs. Provided there is flexibility to allow for individual departures from consensus recommendations and for development of new technologies, applying clinical guidelines in health care can serve both individual patients and society and help to balance their respective needs for informed decision making and for resource allocation. PMID- 2221652 TI - Medical practice guidelines: current activities and future directions. AB - OBJECTIVE: To examine the state of the art in the field of medical practice guidelines, to identify limitations, and to suggest future directions. DESIGN: Informal descriptive survey using a questionnaire administered by telephone, supplemented by comments, by opinions, and by examples solicited from the participating organizations. PARTICIPANTS: Eight prominent organizations representing prototypic approaches to guideline development; these organizations included three medical societies, two health care organizations, two insurers, and one private health benefits management company. RESULTS: Improving the quality of medical care was a stated goal of all eight surveyed organizations. However, their objectives have not been stated in operational terms, reflecting the lesser emphasis placed on methods and means for both implementing guidelines and evaluating their impact on health practices and outcomes. In contrast, several systematic methods for developing guidelines exist. They differ in the stress placed on formal literature reviews, reliance on local as opposed to national experts, and formal methods of group judgment, but no evidence exists on which approaches produce sounder and more usable guidelines. CONCLUSIONS: Guidelines are being vigorously promoted as a means to improve the effectiveness of the health care system. Current initiatives show both strengths and weaknesses. In particular, the attention now paid to the development of guidelines needs to be matched by attention to implementation strategies and to the scientific evaluation of their effectiveness in real clinical settings. Also, more agreement is needed on acceptable methods for developing guidelines, assessing their content, and evaluating their impact on professional behavior, patient outcomes, and health care costs. Fortunately, several initiatives to bring greater order and quality to this field are under way. PMID- 2221653 TI - Intestinal infarction after intravenous cocaine administration. PMID- 2221654 TI - Corticosteroids for asthma. PMID- 2221655 TI - Prostatic cryptococcal infection. PMID- 2221657 TI - Clarification of contaminants in L-tryptophan. PMID- 2221656 TI - Erythropoietin for anemia in Jehovah's Witnesses. PMID- 2221658 TI - Loose connections between peer-reviewed clinical journals and clinical practice. AB - Many important advances in medical care are first reported in the biomedical literature, but physicians find the literature overwhelming and, therefore, are often unaware of advances. This article examines the ways in which peer-reviewed clinical journals contribute to this problem and proposes some solutions for both their editors and clinical readers. Peer-reviewed clinical journals impede the dissemination of validated advances to practitioners by mixing a few rigorous studies (communications from scientists to practitioners) with many preliminary investigations (communications from scientists to scientists). Journals wishing to improve communication with practitioners should feature rigorous studies of the nature, cause, prognosis, diagnosis, prevention, and treatment of disease and should feature sound clinical review articles (communications from practitioners to practitioners). Additional strategies for improving communication between medical scientists and practitioners include improving publication standards for clinical journals, proving more informative abstracts for clinical articles, fostering the development of derivative literature services, and enhancing practitioners' skills in critically appraising the medical literature. PMID- 2221659 TI - [The Oedipus complex and organization of the normal personality]. AB - The parents' task is to get the child to move from his absolute and original narcissism to the awareness of and submissiveness to the principle of Reality, without prejudice to his affective life. This entails a tragic triangular situation that we shall qualify as being Oedipean, although differing from Freud's interpretation. It has a structuring psychodynamic effect requiring complex yet precise mechanisms which entirely proceed from this situation and that we have tried to study thoroughly. The child can thus reach the adult status through access to Reality, and the development of his latent faculties. The Oedipean situation is therefore unique in allowing the progressive making of a normal personality. PMID- 2221660 TI - [Denial and coronary disease. A reconsideration of the denial mechanism in psychosomatic diseases and particularly in coronary disease]. AB - Recent research has shown that patients with life-threatening illnesses have improved chances of survival and enhanced abilities to manage situational anxiety and depression if, instead of recognizing the seriousness of their illness, they employ the psychological defense mechanism of denial. Denial as a coping style provides indeed marked benefits for the patient, at least during acute hospital recovery, but seems to be possibly maladaptative in the long run after hospital discharge. The present study is an attempts to review the different findings related to the use of denial by the coronary patient. The concept and its use are re-examined from the very different standpoints of the patient, the cardiologist and the psychologist, in a psychodynamic, a systemic and a psychosomatic perspective. Even if clinically meaningful, denial is also revisited through both the ethical and the epistemological approaches. PMID- 2221661 TI - [Tutelage and management: better knowledge for a better use]. AB - At present, almost half of tutelages pronounced, are management's tutelages. However, legislation and rules of provision's patronage are complex and appear misunderstood with themselves who regularly use them in their practice. A reminder of legal feasibilities but also of their eventual disadvantages is appeared necessary to the authors. Who can do what and how? The roles of each protagonist are related in detail, with pragmatism. PMID- 2221662 TI - [The pre-revolutionary Penal Code. A tribute to the bicentennial of the 1789 French Revolution]. PMID- 2221663 TI - [Pierre Janet. Disintegrating psychological analysis]. PMID- 2221664 TI - [Synthetic activity in Janet's psychology]. PMID- 2221665 TI - [Manic-depression and reversed genetics]. PMID- 2221666 TI - [Shared delusion: results of a survey of psychiatrists in Western France]. PMID- 2221668 TI - Myoblast diversity and the formation of the early limb musculature. PMID- 2221667 TI - Caldesmon: fragments, sequence, and domain mapping. AB - A summary of the available binding site data is shown in Figure 6 and should be compared with the predicted structures in Figure 5. The blocks of amino acid sequence were those known at the time the cDNA sequencing was being done; they now include the entire head region. The phosphorylation site, indicated here, is a potential site, a consensus sequence, -AXYS(T)-, for the multifunctional calmodulin-dependent kinase. It has not been established that this site is utilized, and it is not clearly related to any of the established binding domains. Exactly how caldesmon regulates the actomyosin interaction and whether it contributes to the latch state is unclear. The organization of the molecule suggests, however, that it could function as a bridge between thick and thin filaments. In support of this idea, our recent efforts to map the smaller non muscle form of caldesmon indicate that it retains the myosin and the calmodulin approximately actin binding domains, but is missing the central repeated region, arguing this region may serve to space the N and C terminal-binding domains in smooth muscle. Work from several laboratories has demonstrated that smooth muscle caldesmon is an elongated molecule with a calmodulin, tropomyosin, and actin binding region at the C-terminus and a myosin-binding domain at the N-terminus. Sequence determination has shown that smooth muscle caldesmon is smaller than previously believed, has demonstrated similarities between caldesmon and troponin T, and has suggested possible calmodulin-binding peptides. The available sequence and domain mapping studies on smooth muscle caldesmon are reviewed. PMID- 2221669 TI - Molecular analysis of the c-myc transcription elongation block. Implications for the generation of Burkitt's lymphoma. PMID- 2221670 TI - The arithmetic of skeletal myogenesis in the chick embryo. PMID- 2221671 TI - Cell lineage segregation during neural crest ontogeny. PMID- 2221672 TI - Analysis of frequency of intermingling between labeled clones in Xenopus embryos. AB - These experiments were designed to provide data that would test alternative hypotheses of the basis of clonal intermingling during early development of Xenopus. Clones were initiated by injection of different fluorescent cell lineage tracers into two blastomeres in the same 512-cell embryo. In order to find out how frequently clonal intermingling or clonal separation developed between the progeny of two ancestral cells at different distances apart, the pair of injected cells was either adjacent, separated by one uninjected cell, or separated by two uninjected cells, chosen at random in the animal dorsal region of the embryo. The final positions of the labeled clones were analyzed at tailbud stages. The results closely match the probability of interclonal mingling predicted by a compartment model, in which two clones intermingle or remain separate as a function of the probability of a clonal restriction boundary developing between them, rather than as a continuous function of the distance between the two cells at the time of labeling. PMID- 2221673 TI - Autonomous expression of the differentiation programs of cells in the cardiac and skeletal myogenic lineages. PMID- 2221674 TI - Macromolecular organization of the extracellular matrix of cartilage. PMID- 2221675 TI - Collagen types and chondrogenesis. PMID- 2221677 TI - Covalent cross-bridge regulation in smooth muscle. PMID- 2221676 TI - Hypertrophic chondrocytes. The terminal stage of differentiation in the chondrogenic cell lineage? AB - Chondrocytes emerging in the limb or other locations during embryogenesis are currently considered terminally differentiated cells and thus represent the last stage of differentiation in the chondrogenic cell lineage. Most chondrocytes, however, undergo further major phenotypic changes during late embryogenesis and early postnatal life as they take part in the endochondral ossification process. During this process, "resting" chondrocytes first enter an active, proliferative phase and then develop into large, round hypertrophic chondrocytes with unique phenotypic traits. The question thus arises as to whether hypertrophic chondrocytes actually represent the terminal stage of differentiation in the chondrogenic lineage. To assess the developmental position of these cells along the lineage, we examined the expression of four genes encoding extracellular matrix components in chondrocytes undergoing endochondral ossification in chicken tibial growth cartilage. We found that the steady-state levels of mRNAs coding for proteoglycan core protein increased in regions of cartilage destined for endochondral ossification. Similarly, type II collagen gene expression increased markedly in proliferating chondrocytes and then returned to basal levels in hypertrophic chondrocytes. As revealed by in situ hybridization, type X collagen gene expression was undetectable in resting and early proliferating chondrocytes and was detectable in hypertrophic chondrocytes. Osteonectin synthesis appeared to characterize chondrocytes in the resting, proliferating, and hypertrophic zones of growth cartilage. The protein was scarce, however, and cell-associated in the former zones, although it was very abundant and matrix-associated in the hypertrophic zone. Clearly, the emergence of hypertrophic chondrocytes during endochondral ossification is accompanied by marked quantitative and qualitative changes in gene expression. Interestingly, these changes occur during or immediately after the period of active chondrocyte proliferation. On the premises of the cell lineage definition proposed by Holtzer, the above data suggest that the hypertrophic chondrocytes represent the terminal stage of differentiation in the chondrogenic cell lineage. PMID- 2221678 TI - Caldesmon and the structure of vertebrate smooth muscle thin filaments. A minireview. PMID- 2221679 TI - Regulation of ATP hydrolysis by caldesmon. A novel change in the interaction of myosin with actin. PMID- 2221680 TI - P wave morphology. PMID- 2221681 TI - Electrocardiography--past and future. A conference. September 8-9, 1989, Nice, France. Proceedings. PMID- 2221682 TI - Myocardial perfusion scintigraphy as an aid in understanding electrocardiographic changes of ischemia and infarction. AB - In summary, myocardial perfusion scintigraphy with either thallium or the isonitriles has added substantially to electrocardiographic definition of both myocardial infarction and acute and chronic myocardial ischemia. Using perfusion scintigraphy, one can define infarct zones, risk zones, and the presence of reperfusion following thrombolytic therapy. When perfusion scintigraphy is combined with physiologic or pharmacologic stress, myocardial ischemia can be documented, irrespective of electrocardiographic documentation of the phenomenon. Delayed imaging may be important for defining viability even in the presence of significant Q waves. Myocardial perfusion scintigraphy provides prognostic evaluation of patients with both acute and chronic coronary syndromes. When the current cumulative experience is looked at critically, it is clear that myocardial perfusion scintigraphy has helped in the development of an understanding of the limitations of electrocardiography in the diagnostic and functional categorization of patients with acute and chronic coronary disease. PMID- 2221683 TI - Endocardial monophasic action potentials. Correlations with intracellular electrical activity. PMID- 2221684 TI - Endocardial and epicardial recordings. Correlation of twelve-lead electrocardiograms at the site of origin of ventricular tachycardia. PMID- 2221685 TI - Signal averaging. PMID- 2221686 TI - Spectral estimation of the electrocardiogram. PMID- 2221687 TI - Autonomic interactions in cardiac control. PMID- 2221688 TI - Circadian variations of electrical properties of the heart. AB - Cardiac refractoriness and electrical inducibility of supraventricular tachycardia (SVT) were assessed at intervals of 1 to 2 hours over a period of 22 hours in 38 patients (25 with paroxysmal SVT). Daily variability of effective refractory period (ERP) had a mean range of 35 +/- 14 mseconds for the atria, 79 +/- 65 mseconds for the AV node, 24 +/- 10 m seconds for the ventricles, 51 +/- 27 mseconds for the retrograde Kent bundle, and 35 +/- 17 mseconds for the antegrade Kent bundle. Between 11 PM and 8 AM there was a significant prolongation of the ERP of the atria (ANOVA, p less than 0.001), AV node (p = 0.002), right ventricle (p less than 0.001), and retrograde Kent bundle (p = 0.005), and a reduction in electrical induction of SVT from 75% to 42% (p less than 0.05) with respect to the first electrophysiologic study. This nocturnal prolongation was preceded by ERP shortening of all explored cardiac sites and by increased tachycardia inducibility between 8 and 10 PM. Six patients with dual AV nodal pathways showed a prolongation of the fast pathway ERP at midnight, whereas conduction through the slow pathway followed an unpredictable daily variability. These data indicate a circadian influence on refractoriness of normal cardiac tissues and accessory pathways that exerted a midnight protection against electrical inducibility of reciprocating tachycardia but a transient arrhythmia facilitation at the evening. PMID- 2221689 TI - Clinical exploration of the autonomic nervous system by means of electrocardiography. PMID- 2221690 TI - Autonomic nervous system and arrhythmias. PMID- 2221692 TI - Irregular dynamics of excitation in biologic and mathematical models of cardiac cells. AB - Excitation and impulse propagation in cardiac tissues are dependent on the heart rate and can occur in extremely complex patterns. In this chapter we present the results of Purkinje fiber experiments and of computer simulations using an ionic (Beeler & Reuter) model for the ventricular cell. We have studied the global rate dependent behavior of cardiac cells through a systematic analysis of their response to single as well as repetitive depolarizing stimuli, and determined the role of nonlinearity in the mechanism(s) of their behaviors. To this end, we devised an analytical difference equation model of cardiac cell excitation which could be used to predict simple as well as chaotic behavior of both the Purkinje fiber and the Beeler & Reuter cell, depending on the stimulation rate. Both experimental and modeling results suggest that the presence of supernormal recovery in cell excitability establishes sufficient nonlinearity so that, during repetitive stimulation, the dynamics of cell response may be regular and predictable when the stimulus magnitude is either very small or very large, or they may be chaotic and very unpredictable when the stimulus magnitude is intermediate. The overall results suggest that the application of nonlinear systems theory to electrophysiology may have importance in the understanding of cardiac rhythm and conduction disturbances, and may have clinical implications as well. PMID- 2221691 TI - The cellular basis of cardiac arrhythmias. A matrical perspective. PMID- 2221693 TI - Electrocardiography. Past, present, and future. PMID- 2221694 TI - Multidimensional quantitation of ventricular repolarization. Static and dynamic characteristics. PMID- 2221695 TI - Quantitative electrocardiography. Standardization and performance evaluation. PMID- 2221697 TI - Computer-assisted analysis of Holter recordings. PMID- 2221696 TI - Computerized electrocardiography. A historical perspective. PMID- 2221698 TI - Electrocardiographic characteristics and main causes of pseudoprimary T wave changes. Significance of concordant and discordant T waves in the human and other animal species. PMID- 2221699 TI - The promise of electrocardiography in the 21st century. PMID- 2221700 TI - The reflex effects of tachycardias on autonomic tone. PMID- 2221702 TI - The predictive accuracy of the electrocardiogram in identifying the presence and location of myocardial infarction and coronary artery disease. AB - In summary, the electrocardiogram is limited in its ability to detect a myocardial infarction. Its sensitivity is compromised seriously by a substantial number of patients (table; see text) with non-Q wave infarction or regression of Q waves. Once a Q wave occurs, the predictive accuracy of those changes, in delineating the location of the infarction, is quite high. The ability of Q waves or ST segment elevation to predict or identify the "culprit artery" is less strong, primarily due to the variation in coronary anatomy commonly found. The relationship between anterior or inferior lead changes and anterior or inferior myocardial damage is close. However, lateral lead changes may more accurately represent anterolateral (I, AVL) or apical (V5-V6) infarction. Tall R waves in anterior precordial leads is most often associated with posterolateral infarction. PMID- 2221701 TI - Electrocardiographic diagnosis of transient myocardial ischemia. Sensitivity, specificity, and practical significance. PMID- 2221703 TI - Positron emission tomography as an aid in understanding electrocardiographic changes of ischemia, infarction, and cardiomyopathy. PMID- 2221704 TI - Presynaptic purine receptors. PMID- 2221705 TI - Eye banking: the Minnesota experience. AB - We present a brief report on the activities of the Minnesota Lions Eye Bank. This eye bank receives and supplies tissue to several midwestern states. In addition, it plays a vital role in providing tissue for research and training at the University of Minnesota. In association with the Department of Ophthalmology, the eye bank is also actively involved in the research and development of various corneal preservation systems. Included below is information relative to procedures used in the eye bank for the selection and collection of donor material; the decontamination, preparation, and storage of corneas; cost of eye bank services; and staff coverage. Also included is some data on the number of eyes received and processed and the eventual uses of the tissues, during the last ten years. PMID- 2221706 TI - Spectral electroretinography in thioridazine toxicity. AB - In three patients with thioridazine toxicity, the electroretinogram (ERG) to red light was found to be below the average normal range. A significant increase in its amplitude appeared with cessation of therapy in two cases. A further deterioration of the ERG amplitude to all stimulus conditions (white, blue, and red lights) occurred when the dose of the medication was increased in the third patient. PMID- 2221707 TI - A case of unilateral posterior ischemic optic neuropathy after radical neck dissection. AB - We present a case of unilateral posterior ischemic optic neuropathy after bilateral radical neck dissection. Etiologic factors are discussed. PMID- 2221708 TI - Fluorescein angiography using ultra-high speed film. AB - We used a new ultra-high speed black-and-white film, Kodak T-MAX P3200 (ASA 3200), in routine fluorescein angiography on 51 patients and one normal volunteer. The increased film speed permitted a lower flash intensity than with other available films. Photophobia was improved subjectively in 25% of patients who had undergone prior angiography at a higher flash setting. In addition, patient cooperation was improved as evidenced by a decrease in the frequency of photographic artifacts and uninterpretable photographs compared with prior angiograms done using Kodak TRI-X Pan film (ASA 400). T-MAX yielded excellent resolution, but its grain size was slightly greater than that of TRI-X Pan. The use of ultra-high speed film and reduced light intensity may benefit the patient and improve photographic quality in some individuals with photophobia. PMID- 2221709 TI - Visual disturbances associated with over-the-counter ibuprofen in three patients. PMID- 2221711 TI - [Provoked oto-emissions. Parameters obtained in normal subjects using Kemp's equipment]. AB - Response parameters relating to the stimulus (click or filtrated bursts), the patient's age and audition curve (physiological presbyacusis) were derived from 3158 provoked otoemission (POE) recordings obtained in normal subjects. Current limits imposed by the device used constitute a factor restricting indications for such devices to the screening of loss hearing in the young child, obviously, but also to the investigation of certain paucisymptomatic hearing disorders presenting with normal or subnormal pure tome audiograms. PMID- 2221710 TI - Branch retinal vein occlusion: the pathogenetic role of blood viscosity. AB - The pathogenesis of branch retinal vein occlusion has not been completely clarified. The role of abnormal blood viscosity in the appearance and evolution of the disease has recently been advocated. We studied 54 patients with long standing branch retinal vein occlusion from a hemorrheologic point of view. Depending on the extension of retinal ischemia, two subgroups were identified. Hematocrit, blood and plasma viscosity, whole blood filterability, cell deformability, and fibrinogen levels were investigated. Thirty-five subjects of similar age, sex, and risk factors of diabetes and hypertension served as controls. Our results showed that blood viscosity is higher in patients with occlusion and particularly in those with severe retinal ischemia. Statistical analysis showed a direct correlation between blood viscosity and hematocrit. PMID- 2221712 TI - [Acoustic distorsion products: technic, reproducibility and audiometric value. A new technic for the clinical evaluation of hearing]. AB - Acoustic distorsion products are sounds emitted by the cochlea, in relation with the outer hair cell properties and the micromechanical properties of the Organ of Corti, in response to an acoustic stimulation by two primairies F1 and F2. Acoustic distorsion product 2F1-F2 have been recorded in two populations: 10 normally-hearing subjects and 10 subjects with pure sensorineural hearing losses. Three points are discussed: (i) the test-retest reliability, (ii) the clinical tolerance and (iii) the clinical applications of this test. PMID- 2221713 TI - [Amyloidosis disclosed by ORL manifestations]. AB - Amylosis is characterized by an infiltration of acellular substance into the tissues. This substance is mainly made of protein molecules. This disease is primary or secondary to general disorders. Its anatomical polymorphism can well involve the ENT system. Its clinical pictures are well known by the ENT specialist. About tow amyloid tumors diagnosed because of oropharyngeous signs, the authors remind the main symptoms at the upper airway and ENT tracts; the local, regional and general treatment will be discussed. PMID- 2221714 TI - [Immunohistology of polyps of the nose and paranasal sinuses. Physiopathologic value]. AB - The pathophysiology of nasal polyposis is yet unclear, but chronic disturbances of the inflammatory pathways may be suspected. Immunological investigations were performed in 3 series of patients: 37 with nasal polyps, 22 with chronic sinusitis, and 15 controls with healthy nasal and sinusal mucosa. Patients with nasal polyps had up to ten times more eosinophil density than patients with sinusitis or healthy mucosa. The average of mast cells and IgE or IgA, M, G plasma cells were not different in the various group. Deposited immune complexes were always absent. These results gave us the opportunity to discuss recent pathogenic theories. PMID- 2221715 TI - [Anatomic and endoscopic studies of the anterior ethmoid]. AB - Introduction of present-day sinonasal endoscopy and progress in endonasal surgery under endoscopic guidance of endoscopy provide for anatomical exploration of the anterior part of the ethmoid bone, which is the crosspoint of the facial sinus draining paths. We propose to present here a simple and logical scheme of the topographical anatomy of the ethmoid bone. Classification of the ethmoidal cells allows to define the structures, whereby appropriate nomenclature may be adopted and certain confusions avoided. Thus, each cell within particular cell groups acquires a specific designation based on its draining paths and location in relation to basal lamellae. Endoscopic analysis also deserves being described in some length, since the panoramic view afforded by currently used optics modifies the image ans requires that the observer develop an "endoscopic eye". We draw attention to the endoscopic anatomical fine points in the crucial area of the bullar "circus". These landmarks come in as necessary guides in surgical practice. PMID- 2221716 TI - [The value of endoscopy in recurrent acute laryngotracheitis in children. Apropos of 406 cases]. AB - Acute laryngo-tracheitis in infants represents a common cause of respiratory distress with stridor accompanied with hospital admission. The prognosis is usually favorable in light of the available medical and environmental management. We performed a retrospective analysis of 1739 case reports from 1974 to 1989 with special attention being paid to infants admitted three times or more for recurrent acute laryngo-tracheitis. An ENT consultation was requested in 406 infants which resulted with an endoscopy being performed. Narrowing of the airway was noted in 75% of cases. Dynamics of fluids explains why a silent lesion becomes symptomatic as soon as an inflammatory process is also present. As there are pathologies which are life-threatening, we advocate routine endoscopy as a precautionary method of investigation, followed by close reassessments, in all cases of recurrent acute laryngo-tracheitis with dyspnea. Preferably, this procedure should be performed between dyspneic episodes. PMID- 2221717 TI - [Choice of methods for reconstruction of the cheek after carcinologic excision based on a retrospective study of 32 cases in 8 years from 1980 to 1987 at the Gustave Roussy Institute]. AB - In this article, after reviewing the different possibilities for cheek reconstruction consecutive to carcinologic excision, we specify the choice method for closure, according to the anatomical type of substance loss incurred. In all cases, endobuccal skin covering is needed. --As regards small lesions, there is no such thing as "the" ideal flap. --As far as tegumental cheeks are concerned, the deltopectoral flap is the choice one. --In case of mucous reconstruction, submental flaps afford elegant solutions. --With large lesions, musculocutaneous flaps are best used. Lastly, it seems that the first surgical treatment (excision, curage and plasty) followed or not by radiotherapy, depending on anatomopathological findings, brings acceptable and prompt restoration of function and morphology. PMID- 2221718 TI - [How many peripheral facial paralyses are manifestations of Lyme disease? A French multicenter study]. AB - The diagnosis of Lyme disease is easy on the basis of clinical features only when it combines migrans chronic erythema, severe root pain affecting the limbs and facial paralysis, above all when bilateral. When pain is transient and slight and when erythema and the tick bite are absent facial paralysis may be mistaken for Bell's palsy. The risk is that of failing to recognise Lyme disease which may subsequently manifest itself as severe neurologic complications minimally sensitive to antibiotics. The multicenter study envisaged is designed to determine the incidence of Borrelia burgdorferi seroconversion in all individuals with a non-traumatic peripheral facial paralysis seen between 1.1.90 and 12.31.90. Serology is difficult to interpret on an individual basis. A large series will be necessary in order to be able to draw reliable conclusions. Two control series will be used: one consisting of a sub-group of facial paralyses with herpes zoster vesicles and the other based upon pairing of two control sera for each Borrelia burgdorferi positive serum. This should show whether Lyme disease need really be feared in presence of an apparently isolated FP. PMID- 2221719 TI - [Extensive fibromatosis of the neck muscles]. AB - Extensive fibromatosis, also called desmoid tumor, is a histologically benign tumor, which is nonetheless serious due to its recurrent character and to its potential for infiltration of neighboring tissues. Extensive surgery is the only effective means of treatment, radiation therapy being used only as a complement. The authors describe an elective location of the lesion in the sheaths of the scalenus muscles. This development is usually observed in young women, as is the case in the observation reported here. PMID- 2221720 TI - [Comparative study of the efficacy and tolerance of prednisolone versus niflumic acid in the treatment of acute sinusitis in adults]. PMID- 2221722 TI - [Post-traumatic decompression of the optic nerve. Ophthalmologic and x-ray computed tomographic evaluation. Results in a series of 23 cases]. AB - Post traumatic optic nerve compression gives a Clinic picture of physiological section. CT Scan is consistent with optic canal lesion when considering direct signs (bony fragments compressing the nerve) or indirect (fractures and hematoma of posterior orbital wall, of posterior ethmoid, and sphenoid). 23 patients had a surgical decompression through transethmoidosphenoidal approach. A lesion of optic canal was found in 22 out of 23 cases. Improvement of vision was noted in 12 cases. PMID- 2221721 TI - [Vestibular compensation. Review of the literature and clinical applications]. AB - Vestibular compensation is an excellent model for the study of plasticity of the adult central nervous system. Therefore it has been the subject of several studies in humans and animals, which will be briefly summed up by the authors. Lesions of the labyrinth or vestibular neurectomy are immediately followed of postural and oculomotor disorders, as well as by dynamic deficits of the various vestibular reflexes (vestibulo-ocular and vestibulonucal reflexes). While the former problems always recede in all species, the restoration of the dynamic properties of vestibular reflexes largely depends upon the species considered, in particular for the vestibulo-ocular reflex. However, this function seems to recover the gain and phase it had prior to the lesion in both humans and monkeys. What is the neuronal substrate of these various deficits? Electrophysiological studies have demonstrated at the acute stage a symmetrical activity between the two vestibular nuclei: on the side of the lesion, the nucleus becomes inactive, while the resting discharge of the contralateral vestibular neurons is increased. Following compensation, symmetric activity is restored between both nuclei due to the regeneration of a new basic discharge in the deafferented neurons. The matter of vestibular compensation can therefore be formulated as follows: which mechanisms enable a central neuron inactivated du to the suppression of most of its excitatory afferences to recover a normal spontaneous activity? Several hypotheses, either pre- or postsynaptic, are currently put forward. Presynaptic hypotheses consider the role of the various afferences of the vestibular nuclei, ie. visual, proprioceptive, commissural, cerebellar and other afferences. In fact, the vestibular nuclei are not merely relays between the labyrinthine receptors and the nuclei of the oculomotor nerves, but actually form real sensorimotor integration centers. Besides the afferences from the vestibular nerve, they receive several other sorts of information, including visual and spinal proprioceptive inputs. An increase in the activity of these afferences, a sprouting of their axon collaterals, may favor the return to a normal basic discharge of the central vestibular neurons. The postsynaptic hypotheses involve either a change in the intrinsic membrane properties of the central vestibular neurons following the lesion, or an increase in the number of receptors located on their surface. More specifically, denervation supersensitivity of the glutamatergic receptors has been put forward as the possible origin of vestibular compensation. PMID- 2221723 TI - [The value of pharyngo-esophageal manometry in the study of deglutition disorders]. AB - Pharyngoesophageal manometry is an excellent tool for the study of pharyngeal swallowing disorders, and allows quantifying the various anomalies. The comparison of pre- and postoperative results allows better differentiation of the indications for myotomy or myectomy of the cricopharyngeal muscle. On the basis of a series of 10 cases with sufficient distance in time, the operation can be regarded as even more beneficial as the manometric anomalies are confined to the sole upper esophageal sphincter. PMID- 2221724 TI - [Mouth and pharyngeal hyperalgesic syndromes in AIDS]. AB - In a series of 12 patients suffering from an HIV infection, including 9 with confirmed AIDS, who complained about pharyngeal pain in a fixed site, having a progressive intensity and not relieved by antalgics and the specific treatments that were prescribed empirically, and for whom etiological investigation yielded negative results, Thalidomide proved to be the only effective means of healing the exulcerated, nail-mark lesions or the ulcerated, budding, neoplastic-like lesions, and of completely suppressing pain. PMID- 2221725 TI - [Contribution of immunologic technics to the characterization of lethal midline granuloma of unknown origin]. AB - The lethal midline granuloma is a clinical entity characterized by a relentless ulceration of the upper airway involving the nose, the palate and the face, without any demonstrable etiology. We have applied the cell membrane immunostaining techniques to twelve cases. According to the results, it seems that most of the cases are in fact T-cell lymphomas with membrane staining consistent with either precursor or mature lymphoid T-cells. Some cases, however, exhibit an immunostaining pattern compatible with other origins, the proliferating cells belonging either to the B lymphoid or to the histio-monocytic lineages. We conclude that the lethal midline granuloma is an heterogeneous group of neoplastic diseases, in the most part close to a T cell lymphoma, but with a remarkable clinical unity. PMID- 2221726 TI - [Frontal and ethmoidal mucoceles. Apropos of 17 cases]. AB - We have been studying 17 cases for operated mucoceles over a period of 4 years. Usual predisposing factors are often present, however we found no underlying malignant tumor revealed by a mucocele. Surgical treatment always included exclusion and filling with bone grafts in case of frontal involvement. Small ethmoidal lesions without symptom found on the CT scan are worrying because of their potential deterioration; in such cases, our attitude has been surgical. PMID- 2221727 TI - [Sinusitis during intensive care. Prospective studies]. AB - Two series of ICU patients, the first one with nasal endotracheal intubation, the other one with a tracheostomy, were included in a prospective and comparative study with repeated CT scans of the sinuses. Radiological sinus involvement is seen in both groups almost constantly; purulent sinusitis are often seen in both series. Unexplained fever should make us look for a sinusitis, even in patients with early tracheostomy. Moreover, our results ask for more study about associated causes, apart from nasal endotracheal intubation. PMID- 2221728 TI - [Endocranial complications of chronic otitis in adults]. AB - 47 patients with intracranial abscess were admitted in the neurosurgical department of Professor Fohanno Pitie-Salpetriere Hospital, between 1973 and 1989. Most often central abscesses were found. In 9 cases, the ear was the primary septic focus: 3 chronic otitis with cholesteatoma, 6 chronic otitis without cholesteatoma. In most cases, treatment included: Immediate drainage, Delayed surgery for the primary focus. PMID- 2221729 TI - [Value of the administration of trimetazidine associated with hemodilution in the treatment of sudden deafness. Report of a multicenter study]. AB - Sudden deafness is a medical emergency, for which etiopathology is ill-known and no therapeutic consensus exists. This study is aimed at demonstrating that a greater audiometric gain can be achieved if trimetazidine, a major cellular anti ischemia agent, is associated with hemodilution, than when the treatment is based on hemodilution only. 42 patients suffering from sudden deafness were all treated with hemodilution before their 7th day of deafness, half of them being given 3 tablets of trimetazidine daily in addition and the other half placebo, during one month. The results of this double-blind trial demonstrate an additional audiometric gain of 10% in the trimetazidine group for all frequencies, as well as a higher percentage of total recovery, ie. 63% vs. 47% in the placebo group. No particular sensitivity to treatment was noted according to the shape of the audiometric curve or in the case of initial cophosis, known to be of poor prognosis. The statistic significance was not established due to the small number of cases. The association of trimetazidine and hemodilution therefore seems to be an interesting therapeutic approach for sudden deafness, owing to the clinically appreciable audiometric improvement we have noted. PMID- 2221730 TI - Teflon versus thyroplasty versus nerve transfer: a comparison. AB - Surgical rehabilitation of the paralyzed larynx is currently performed by Teflon injection, thyroplasty, and reinnervation techniques. Proponents of the two newer techniques maintain that they are preferred to Teflon injection because superior phonatory quality is achievable. This paper was written in an attempt to dissect the issues regarding this question. Teflon remains the quickest and least expensive procedure, but further experience with stroboscopic and other voice analyses reveals that the other procedures demonstrate some superiority in phonatory quality over Teflon. In this author's hands, the nerve transfer offers the best opportunity to achieve a normal phonatory voice. In addition, it is the only one of the three procedures that leaves the vocal cord entirely undisturbed- important in the event one of the other two procedures becomes necessary. PMID- 2221731 TI - Endoscopic laser arytenoidectomy revisited. AB - Arytenoidectomy is currently the most reliable method of treating patients with bilateral vocal cord paralysis. Although both endoscopic and external approaches have been described, the endoscopic laser technique is more desirable because it requires no incision and allows for the immediate assessment of airway size. Eleven patients with bilateral vocal cord paralysis treated by endoscopic laser arytenoidectomy were presented in 1984. At that time, 10 of the 11 patients had been successfully decannulated. Follow-up on that group of patients revealed that 7 of the 10 successfully treated patients remain decannulated with a good airway, although 2 of these patients required a revision procedure to excise a granuloma. One patient failed at 15 months and has failed two subsequent revision operations, and 2 patients have been lost to follow-up. Since 1984, 17 additional patients with bilateral vocal cord paralysis have been treated by the authors using the same endoscopic laser arytenoidectomy technique; all have been successfully managed, with a minimum follow-up of 3 years. The technique of this operation will be reviewed. This study demonstrates the clinical usefulness of endoscopic laser arytenoidectomy in the treatment of bilateral vocal cord paralysis. PMID- 2221732 TI - Laryngeal framework reconstruction with miniplates. AB - Defects of the laryngeal framework after trauma, cancer, and thyroplasty have been reconstructed with mini-reconstruction plates. Six patients had miniplates used to repair the thyroid cartilage defect after type I thyroplasty to prevent lateralization of the Silastic implant; three patients had miniplates used after hemilaryngectomy to bridge the thyroid cartilage remnants, resulting in better deglutition after hemilaryngectomy; and three patients had miniplates used to repair laryngeal fractures. The plates were tolerated well by the patients; there were no major complications. Rigid fixation using miniplates for laryngeal reconstruction has unique advantages over the use of wires. It offers the advantages of rigid and immediate stabilization with the ability to bridge large defects. It can be an alternative to existing techniques of laryngeal reconstruction. PMID- 2221733 TI - Combined laryngeal framework medialization and reinnervation for unilateral vocal fold paralysis. AB - The laryngeal framework-Silastic implant technique has become an increasingly attractive alternative to Teflon injection, particularly when there is fixation of the cricoarytenoid joint or the defect to be corrected is larger than usual; but it does not restore ability to change tension in the vocal fold. Unilateral vocal fold reinnervation can overcome this drawback and, when used in conjunction with surgical medialization, may offer return of function very close to normal. Twenty-nine patients with unrecovered unilateral vocal fold paralysis and/or fixation of the cricoarytenoid joint have been managed by use of a Silastic implant combined with unilateral vocal fold reinnervation with no complications. Voice improvement has been assessed on preoperative and postoperative voice recordings. The combined surgical techniques for reinnervation and a modification of Silastic implantation via the laryngeal framework approach are reported. PMID- 2221734 TI - Auditory brain stem implant: effect of tumor size and preoperative hearing level on function. AB - The auditory brain stem implant is an investigational device designed to provide hearing sensations to patients without functioning auditory nerves. We analyzed results from 17 implants in 15 patients to determine if tumor size or preoperative hearing level might be related to proper device function. We found no significant correlation between preoperative hearing level or tumor size and device function. We also found no significant correlation between preoperative hearing level and tumor size in these 15 patients. PMID- 2221735 TI - Cochlear implant flap complications. AB - In a series of 52 patients who received cochlear implants, 4 patients suffered flap complications (7.7%). The problems encountered involved the postauricular flap and were usually minor in nature. None required explantation as a direct result of these complications. Flap ischemia in a patient with Cogan's syndrome and vasculitis, two cases of suture extrusion with one having exposure of the implant, and a case of receiver unit magnet extrusion repaired with a vascularized pericranial flap based upon temporalis muscle are presented. Flap design in patients who have had postauricular incisions demands special consideration. Principles useful for avoiding complications as well as their management are discussed. PMID- 2221736 TI - Percutaneous pedestal in cochlear implantation. AB - Direct electrical connection between an external sound-processing device and intracochlear electrodes is accomplished via a percutaneous pedestal. Patient pedestal complaints and experience have been recorded. Pedestal problems have been classified into six classes, with class 0 indicating no problems and the severity of problem increasing in classes 1 through 4. Class 5 indicates pedestal trauma. No class 5 problems were encountered. At 48 months of experience, 53% of patients were class 0 and 26% were class 1. The pedestal experience is detailed in the paper. The percutaneous pedestal has been found to be a well-tolerated, efficient system for information transfer in cochlear implant patients. PMID- 2221737 TI - Further studies on the effects of magnetic resonance imaging fields on middle ear implants. AB - We investigated the effects of magnetic resonance imaging (MRI) fields on 21 stapedectomy prostheses and other middle ear implants and two different receiver stimulator modules from 22-channel cochlear implants. None of the middle ear implants was displaced by the magnetic field, except for one platinum-stainless steel stapedectomy piston. Magnetism was not induced in any of the middle ear implants subjected to prolonged exposure in the MRI scanner. We conclude that MRI could pose a hazard to patients who have had stapedectomy using certain platinum stainless steel piston prostheses and to patients with cochlear implants. Magnetic resonance imaging should pose no hazard to patients who have had the other middle ear implants reported on in this and our previous investigation. PMID- 2221738 TI - Vestibular recruitment in Meniere's disease. AB - The aim of this study was to search for vestibular recruitment in a sample of patients with Meniere's disease. Recruitment was defined as an abnormal growth of response with increasing stimulus intensity. Twenty-nine patients were tested with sinusoidal rotation of three different magnitudes at four different frequencies. We also searched for auditory recruitment in each patient via tests of auditory brain stem responses, acoustic reflexes, and loudness balance and discomfort level. Analysis of vestibular responses indicated, on average, a linear relationship between stimulus magnitude and response magnitude, ie, doubling the stimulus magnitude resulted in twice the response magnitude. Meniere's patients did not yield results significantly different (although they were more variable) from those of the normal subjects. The vestibular responses of patients with auditory recruitment did not differ systematically from those of patients without auditory recruitment. We conclude that vestibular recruitment, if it exists in patients with Meniere's disease, is not demonstrated by sinusoidal rotational testing. PMID- 2221739 TI - Histopathologic study of otitis media in individuals with head and neck tumors. AB - Five temporal bones, each including the eustachian tube, were obtained from five adults with advanced malignant tumors of the head and neck. The specimens were from the side on which the tumor had occurred. Otitis media had been detected clinically in two cases, and was detected histopathologically in the other three. We discuss the possibility that otitis media might have been caused by tumor invasion of the paratubal area, by postoperative inflammation in the nasopharynx, or by an inflammatory reaction of tubal structures to radiotherapy, or that these conditions may have coexisted. PMID- 2221740 TI - Internal auditory canal enlargement in Paget's disease appearing as bilateral acoustic neuromas. PMID- 2221741 TI - Histopathologic grading of salivary gland neoplasms: I. Mucoepidermoid carcinomas. AB - Histopathologic grading of salivary gland neoplasms has been done with various degrees of success and hence various degrees of acceptance among pathologists and otolaryngologists-head and neck surgeons. Given their histopathologic diversity, three carcinomas--mucoepidermoid, adenoid cystic, and acinic cell--would seem to be suitable candidates for grading. In this, the first of a three-part series, the authors present a three-level grading scheme for mucoepidermoid carcinomas. It combines histocytologic and growth features of the carcinomas that independently or together, in other grading proposals, have shown prognostic value. PMID- 2221742 TI - Laryngotracheal reconstruction with composite nasal septal cartilage grafts. PMID- 2221743 TI - Excessive nasality or hypernasality as twang quality that is made in the nose. PMID- 2221744 TI - [Evaluation of cutaneous risks of the Pill]. AB - Despite the fact that about 150 millions women must have taken hormonal contraceptives all over the world since the 1960s, the risk/benefit ratio of this birth control method has yet not been reliably assessed. The side effects of the pill on the skin do not pertain, in general, to those (like thrombo-embolism or, perhaps, breast cancer) which might be life-threatening, but they are probably more frequent and may have a potential to alter the quality of life of women who use it. The aim of this paper is to review the dermatological effects of hormonal contraceptives from the point of view of everyday prescribing, with the emphasis on the quality of life of patients. The reported side effects of the pill are therefore classified according to their real or probable frequency, not to their severity or the theoretical importance of their mechanisms. As it would be unwise to speak of the risks without consideration for the benefits, an attempt is made to compare the dermatological safety profile of oral contraceptives to that of other birth control methods (barrier contraceptive methods, intrauterine devices, etc.) on the one hand; on the other hand, one insists upon the fact that the pill in itself may have health benefits, general (reduction in the incidence of some cancers) or dermatological (e. g. an effect on acne). PMID- 2221745 TI - [Epithelio-lymphohistiocytic tumor. Apropos of 3 cases]. AB - We report three cases of epithelio-lympho-histiocytic tumour with very original histological features. The patients were young adults presenting with a nodular lesion on the face which had been present for several years. No recurrence was observed after surgical excision. Histologically, the dermal lesion consisted of epithelial pouches edged with a few layers of basal-like cells and filled with lymphocytes and large clear cells. Relations were found between these lobules and hair follicles, and rudiments of piliary differentiation were noted. The stroma was dense and infiltrated by small lymphocytes and large clear cells. An immunohistochemical study showed marking of the large clear cells by the S 100 protein, which suggested that they were Langerhans cells. The lymphocytes were recognized by the common panleucocyte antibody. The KL 1 antibody marked a few isolated cells within the lobules, but not the basal-like cells. These cases seemed to be similar to the 7 cases reported in the literature by Santa-Cruz and Barr who used the term lymphoepithelial tumour of the skin. We felt justified in putting the stress on the histiocytic component of this tumour and calling it epithelio-lympho-histiocytic tumour. We agree with these authors that this is a tumour of the appendages of the skin and in particular the hair. PMID- 2221746 TI - [Unusual complication of liposuction (atypical cutaneous mycobacteriosis?)]. PMID- 2221747 TI - [Cowden's disease. Adenomatous polyps. Periorifichal lentiginosis]. PMID- 2221748 TI - [Bullous pemphigoid-multiple sclerosis association. A case report]. PMID- 2221749 TI - [Propionibacterium acnes septicemia in T lymphoblastic lymphoma]. PMID- 2221750 TI - [What is your diagnosis? Naevus vascularis mixtus]. PMID- 2221751 TI - [Influence of ultraviolet rays on the immune system]. PMID- 2221752 TI - [Cheilitis and lip lesions artificially induced]. PMID- 2221753 TI - [Cutaneous manifestations of infections in newborn infants]. PMID- 2221754 TI - [Proceedings of the 48th yearly meeting of the American Academy of Dermatology in San Francisco, 2-7 December 1989]. PMID- 2221755 TI - Biology of Plasmodium merozoites with special reference to the chemoresistance of Plasmodium falciparum. PMID- 2221756 TI - [Effects of Saccharomyces boulardii yeast on trophozoites of Entamoeba histolytica in vitro and in cecal amebiasis in young rats]. AB - Lyophilized and rehydrated Saccharomyces boulardii yeasts were administered to young rats previously inoculated into the cecum with Entamoeba histolytica. The numbers of diseased young rats and the severity of the infection, assessed from the appearance of the cecum and its content of mucus and amebae, were significantly reduced by the treatment. The lesions observed resembled those seen in the untreated controls, although healing was faster in the treated animals. Saccharomyces boulardii had no intrinsic amebicidal action in vitro. PMID- 2221757 TI - A technique for identification of cercariae of Schistosoma haematobium, S. curassoni, S. bovis and S. intercalatum. AB - The chaetotaxy of 84 samples or isolates of Schistosoma spp. from western or central Africa has been studied. Three indices were calculated for cercariae of each sample; their average value, the skewness and kurtosis of each indice was established. Each species (S. haematobium, S. curassoni, S. bovis and S. intercalatum) was discriminated with nine variables. The present work gives information to assess, specific diagnosis with simple calculations easily achieved on a small computer. PMID- 2221758 TI - Broncho-pulmonary helminths of chamois (Rupicapra rupicapra parva) captured in North-West Spain: assessment from first stage larvae in faeces and lungs. AB - The bronchopulmonary helminths of 66 chamois (49 males and 17 females), captured in various parts of the Cantabrian mountain range (N. W. Spain) in the autumn of 1983, and in the summer and the autumn of 1984, were studied. The animals were adult and aged between 2 and 16 years. The lungs, trachea and faeces from the last section of the intestine were taken from each animal individually. The trachea and pulmonary larval nodules were dissected. First stage larvae (L-I) were obtained from finely cut up pulmonary tissue and from faeces by migration. The number of larvae I per gram varied between 0.08 and 2,662 (mean = 151.5 +/- 59.5 s. e.) in the faecal samples, and between 0.03 and 1,733 (mean = 65.2 +/- 32.4 s. e.) in the pulmonary ones. There was a low correlation between the two sets of data. When taking into account age and sex, no statistically significant differences were observed in relation to the number of larvae/gram found either in faeces or in pulmonary tissue, while there were statistically significant differences when considering the periods of sampling and reserve of origin, in relation to the larvae found in faeces and lungs, respectively. Infections by three nematodes (Neostrongylus, Muellerius and Protostrongylus) were more common than those produced by two or one, in the lungs as well as in the faeces. The most common genus was Neostrongylus, followed by Muellerius, and no Cystocaulus or Dictyocaulus larvae were found. PMID- 2221759 TI - The fate of the filaria Monanema martini in two rodent hosts: recovery rate, migration, and localization. AB - In Meriones unguiculatus, the recovery rate of 80 inoculated larvae was low (about 20%) and irregular. In the natural host Lemniscomys striatus, the recovery rate was about 50% with inoculated doses of 30, 80 or 400 L3, but slightly higher for 400 L3. This rate was constant from day 2 to month 8 post infection (p.i.). When 7-9 reinoculations were performed in one year, the recovery rate of the late inoculation was of only 14%. After subcutaneous inoculations, larvae penetrated into the peripheric lymphatic vessels from hour 6 p.i. and migrated to the lumbar and mesenteric lymph nodes; this first migratory phase was achieved 5 days p.i. Later, the larvae migrated into the digestive tract lymphatic system. Filarial localization did not depend upon the L3 dose: half were found in the caecum and anterior colon (3 cm) wall, and half were distributed in the posterior colon, mesentery and small intestine. A small number (3-5%) of the filariae were found in the pulmonary blood vessels, as a result of accidental migration by the thoracic canal. A similar phenomenon is known in the lymphatic filariae Brugia spp. in rodents and Conispiculum flavescens in a lizard. Several arguments suggest that the genus Monanema is fundamentally lymphatic. Migrations and life of filariae in the lymphatic system seems to be more usual than it is generally admitted. In onchocerciasis, this may at least partially explain the lymphopathology of the inguinal region. PMID- 2221760 TI - The response of general surgeons to HIV in England and Wales. AB - The prevalence of HIV in the UK has been estimated to be 1 in 1000 of the population. Surgeons are at particular risk of occupational transmission from infected blood. To determine the effect of HIV on surgical practice we sent a questionnaire to 681 general surgeons in England and Wales; 450 replied (66%). Of those who replied, 42% were aware of having operated on an HIV-infected patient at least once, and 28 had recognised self-injury in such circumstances; 79% attempted to identify HIV-infected patients preoperatively, though many depended on clinical suspicion alone, which is known to be unreliable. Of those who had operated on a seropositive patient, 90% reported taking special precautions to avoid blood contact and minimise sharps injuries for such cases. The majority wore double gloves, eye protection and fluid-resistant gowns, but only a minority reported changes in surgical technique. Half had made no changes in procedures or technique when operating on patients not identified as being at risk of HIV infection. Among a wide variety of comments made by the surgeons, the commonest was a call for facilitation of HIV testing prior to surgery. This survey indicates that surgery on HIV-infected patients is not restricted to specialist centres. We review the means of identifying HIV-infected patients, the precautions that can be taken to minimise HIV transmission during surgery, and the possible influences of HIV status on surgical decisions. We conclude that the prevalence of HIV among surgical patients is being underestimated at present, that several simple changes in surgical technique should be adopted generally, and that there is limited value in preoperative HIV testing, though this may become more useful in the foreseeable future. PMID- 2221761 TI - Local audit in vascular surgery. AB - A 2-year audit of the Southampton Vascular Unit showed marked discrepancies in workload from nationally accepted figures. All forms of reconstructive surgery except emergency aortic aneurysm grafting were performed more frequently than expected. The vascular population is elderly and at high risk from major surgery. Mortality was appreciable in all major vascular procedures and usually cardiac or renal related. The elderly population and resulting workload is likely to increase in the near future. The role of local audit in vascular surgery is emphasised. PMID- 2221762 TI - Postoperative muscle strength. AB - This study investigates the role of motivation in voluntary strength measurements during the postoperative period. Thirty patients underwent surgery which was deemed minor, intermediate or major in severity. Before operation and on the 4th postoperative day measurement of grip strength, maximal voluntary and maximal tetanic (stimulated) contraction of adductor pollicis and assessment of mood were recorded. These investigations were also repeated on the 7th postoperative day in those who had major surgery. No patient had postoperative complications. Minor surgery had no influence on any of the values. Those who underwent major surgery showed significant reductions in grip strength, maximal voluntary contraction and mood; however, maximal tetanic contraction was unaffected. The results in the intermediate group were similar to the major group, although mood depression was less marked. Real strength of a hand muscle appears to be unaltered even by major surgery, but voluntary muscle force is decreased by intermediate and major surgery, and correlates with the patient's subjective state of well-being. PMID- 2221763 TI - A comparison of danazol and placebo in the treatment of adult idiopathic gynaecomastia: results of a prospective study in 55 patients. AB - In an attempt to define the efficacy of danazol in the treatment of idiopathic gynaecomastia, 55 patients were enrolled into a randomised double-blind comparison of danazol 200 mg twice daily for 3 months against placebo. The results of 52 patients were evaluated, three patients being excluded because of protocol violations. Danazol improved breast tenderness to a significantly greater degree than did placebo (P = 0.022, danazol vs placebo) and was associated with statistically significant improvement in the degree of gynaecomastia and in its measured size (P less than 0.05). The intended management of patients who had received danazol was less likely to be surgery compared to the placebo group when assessed at the end of treatment (27% vs 50%). Minor side effects were common in both groups, but significant weight gain was noted in the danazol group alone. If there is no urgent need for rapid resolution of gynaecomastia, danazol 200 mg twice daily can provide effective control of symptoms and may obviate the need for surgery. PMID- 2221764 TI - A prospective study of bilateral inguinal hernia repair. AB - A prospective study of outcome after inguinal hernia repair in patients undergoing simultaneous repair of bilateral hernias (n = 31), sequential repair of bilateral hernias (n = 5), and unilateral hernia repair (n = 75) is reported. There were no differences in wound complications, post-operative respiratory complications, or other adverse effects in the three groups. Operating time was similar in the unilateral and bilateral simultaneous repairs (median 55 min), but was longer (100 min) for the combination of two sequential repairs. Hospital stay was shortest for patients undergoing unilateral repair (2 days) but was less with bilateral simultaneous repair (4 days) than after two sequential repairs (total of 6 days). There were 12 (11%) wound complications of which five (5%) were infections. There was no difference in complication rate between unilateral and bilateral hernia repair. Postoperative recovery was assessed prospectively and was recorded at 1 month. There was no difference between unilateral and bilateral simultaneous repairs in the number of days before the patient was able to climb stairs easily, drive a car or return to work. The duration of the requirement for analgesia was similar in each group. We conclude that bilateral simultaneous hernia repair can be carried out with no greater morbidity than a unilateral repair, and the return to normal activity is as rapid. Bilateral hernias should be repaired simultaneously rather than sequentially. PMID- 2221765 TI - McBurney's point--fact or fiction? AB - Anthropometric measurements were performed on 51 normal, supine, barium enema examinations to determine the position of the lower pole of the caecum and the base of the appendix relative to palpable bony landmarks (the anterior superior iliac spine and the symphysis pubis). Four quadrants were defined (iliac, umbilical, inguinal and pelvic) by the intersection of the right lateral line and the interspinous line (the line joining the left and right anterior superior iliac spines). The position of the lower pole of the caecum was iliac in 12%, inguinal in 37%, and pelvic in 51%. The appendix or appendix stump was visualised on 53% of the barium examinations. The position of the appendix was iliac in 15%, umbilical in 15%, inguinal in 11%, and pelvic in 59%. The positions of the lower pole of the caecum and base of the appendix are lower and more medial than previously described. 70% of appendices were found to lie inferior to the interspinous line, contrary to established surgical teaching, which assumes McBurney's point to be the surface landmark for the appendix. PMID- 2221766 TI - The role of the high dependency unit in postoperative care: an update. AB - The current experience of a high dependency unit established 5 years ago for the postoperative care of high-risk patients undergoing surgery is reported. The resource implications and contributions to the safety and quality of post operative care, particularly pain relief, are described. PMID- 2221767 TI - A simple technique for successful primary closure after excision of pilonidal sinus disease. AB - Primary closure after excision of postanal pilonidal sinus disease frequently has been complicated by wound break-downs. Healing by second intention takes many weeks and requires supervised wound care. A simple technique has been developed which has resulted in primary healing in 28 of 31 patients treated in a 5-year period. Sepsis and haematoma formation, the causes of wound breakdown after pilonidal sinus excision, have been prevented by preoperative preparation, prophylactic antibiotic administration, wound irrigation with povidone-iodine and simple skin closure over a Redivac suction drain for at least 4 days. This series suggests that primary closure can be successful using the technique described. PMID- 2221768 TI - Smooth muscle tumours of the alimentary tract. AB - Neoplasms arising from smooth muscle of the gastrointestinal (GI) tract are uncommon, comprising only 1% of gastrointestinal tumours. A total of 51 cases of smooth muscle tumour of the GI tract were analysed; 44 leiomyomas and 7 leiomyosarcomas. Lesions occurred in all areas from the oesophagus to the rectum, the stomach being the commonest site. Thirty-six patients had clinical features referable to the tumour. The tumour was detected during investigation or management of an unrelated disease process in 15 patients. The clinical presentation varied depending on tumour location, but abdominal pain and GI bleeding were the commonest presenting symptoms. The lesion was demonstrated preoperatively, mainly by endoscopy and barium studies, in 27 patients. Surgical excision was the treatment of choice, where possible. There was no recurrence in the leiomyoma group but four patients died in the leiomyosarcoma group. Although rare, smooth muscle tumours should be considered in situations where clinical presentation and investigations are not suggestive of any common GI disorder. The preoperative assessment and diagnosis is difficult because of the variability in clinical features and their inaccessibility to routine GI investigation. It is recommended that, where possible, the lesion, whether symptomatic or discovered incidentally, should be excised completely to achieve a cure and prevent future complications. PMID- 2221769 TI - A technique for monitoring evoked potentials during scoliosis and brachial plexus surgery. AB - A total of 40 patients undergoing scoliosis or brachial plexus surgery had bipolar electrodes inserted preoperatively in the cervical epidural space located by the 'hanging drop technique'. The angle of approach to the space was different for each spinal interspace used. Good quality recordings were obtained of SSEPs with no long-term complications and we recommend this as a safe technique. PMID- 2221770 TI - Local analgesia for infant pyloromyotomy. Does wound infiltration with bupivacaine affect postoperative behaviour? AB - A series of 20 infants undergoing general anaesthesia for pyloromyotomy were studied in a randomised, blind and controlled trial to determine the postoperative behavioural and cardiorespiratory effects of wound infiltration of bupivacaine. Ten infants received bupivacaine (0.6 ml/kg, 0.25% = 1.5 mg/kg) injected intradermally into the wound during general anaesthesia and 10 infants received general anaesthesia only. Postoperatively, an independent observer assessed conscious level, crying, posture and facial expression using a simple numerical scoring system, and also recorded heart and respiratory rates over a 2 h period. Infants who had received bupivacaine were observed to have higher respiratory rates and behaviour scores, although these differences were not statistically significant. These results indicate that wound infiltration with bupivacaine offers no obvious advantage to infants following pyloromyotomy. PMID- 2221772 TI - Aortocaval fistulas and the use of transvenous balloon tamponade. AB - Six cases of acute aortocaval fistula are reported, which illustrate the difficulties of diagnosis and management in a rare life-threatening condition. Five cases arose from spontaneous rupture of aortic aneurysms and one from trauma. In four cases the diagnosis was made before surgery. Useful diagnostic features included inappropriate jugular venous distension in five patients, lower abdominal and trunk cyanosis in three patients and a palpable thrill in three patients. Preoperative diagnosis permitted attempts to control venous haemorrhage in three cases, one by balloons through the aortic sac and two by transvenous positioning of balloon catheters in the vena cava before aortic opening. The use of transvenous balloon catheters was found to be helpful in reducing haemorrhage. Four patients left hospital alive. Preoperative recognition of the signs of an acute aortocaval rupture and preliminary balloon tamponade appear to be valuable in the management of acute aortocaval fistulas. PMID- 2221771 TI - Thoracoabdominal total gastrectomy in the management of adenocarcinoma of the cardia. Is it worth it? AB - A series of 47 consecutive patients with adenocarcinoma of the gastric cardia presenting between 1982 and 1987 have been reviewed. Of these, 38 patients were eligible for surgery (operability rate of 80.85%) but only 25 patients underwent potentially curative resection (resection rate of 65.7%). The disease was extensive at the time of operation, with only two patients (8%) having node negative tumours. The mean hospital stay for patients undergoing resection was 21 days. There were 15 major complications in 10 patients undergoing resection, but a zero 30-day mortality rate. The prognosis of those patients undergoing radical resection remains dismal. No patient survived longer than 30 months, 80% were dead within 1 year. Tumour recurrence and metastases were documented in 13 patients (52%). In the unresectable group there were two deaths from intubation (9%). The mean hospital stay for this group of patients was 12 days. The mean duration of survival in the group was 5.4 months, 70% of patients dying within 6 months and 95% dead within 1 year. The value of radical surgery in patients with adenocarcinoma of the gastric cardia is questioned. PMID- 2221773 TI - Clinical and pathological effects on the rabbit's eye of some plant-derived ophthalmic swabs. AB - The stems of corn, millet, sugar cane and the banana leaf frond excite some clinical and pathological effects in the rabbit's eye when implanted either into the anterior chamber (AC) or subconjunctivally. These effects have not been sight threatening. The materials can either be left to be cleared by the body's phagocytes when they produce mild inflammatory reaction or removed surgically if the inflammatory response is moderate when fragments have been left intraocularly. PMID- 2221774 TI - Blood transfusion and surgery: the effect of growth of a syngeneic sarcoma. PMID- 2221775 TI - Optimal operative treatment in acute septic complications of diverticular disease. PMID- 2221776 TI - The incidence of congenitally absent foot pulses. PMID- 2221777 TI - Educating adults: principles for postgraduate education in surgery. PMID- 2221778 TI - [Boerhaave's syndrome]. AB - Spontaneous esophageal perforation (Boerhaave syndrome) is a life-threatening emergency. It usually has misleading clinical manifestations and causes severe complications. In the presence of the clinical manifestations: vomiting, pain, emphysema, this diagnosis must be considered and confirmed by radiological evaluation of the chest and the esophagus. We report two cases and we describe the severity of this syndrome, its cause, its pathogenesis, and its characteristic clinical features and radiological signs. PMID- 2221779 TI - [Agenesis of the right lobe of the liver. Apropos of a case]. AB - The authors describe a recent case of agenesis of the right lobe of the liver. Such cases are rare and can be diagnosed with state of the art imaging modalities, ultrasound and computed tomography, which permit early diagnosis and help avoid liver complications of cirrhosis, cholangiocarcinoma and hepatoma. This type of congenital anomaly can be associated with biliary tract disease, portal hypertension or other congenital anomalies. PMID- 2221781 TI - [Fracture of the base of the first metacarpus]. AB - The authors report a group of 73 cases of fractures of the base of the first metacarpal treated between 1974 and 1989. Fifty-three articular fractures (73%) and 20 non-articular fractures are described. Sixty-eight patients were treated surgically: 49 diverging pin insertions were used, 15 Lars Thoren technique, 5 rigid osteosyntheses with AO miniaturized material. Forty-two patients were seen again after one year or more. We classify the results as follows: very good: 29 (69%), good: 10 (24%), bad: 3 (7%). The relative simplicity, the reliability and the good results of the double diverging pin insertion lead the authors to apply this method in most fractures of the base of the first metacarpal, either articular or extra-articular. PMID- 2221780 TI - [Hemangiopericytoma. Apropos of a case]. AB - Haemangiopericytomas are ubiquitous tumours with an equivocal clinical and radiological expression. They generally have a slow course and the lesions are usually revealed by a non-specific mass effect on adjacent structures. The authors report a case of subcutaneous haemangiopericytoma of the elbow which presented clinically as a vascular malformation. Amongst the various imaging techniques performed, only arteriography defined the vascular nature of the lesion and should have suggested the diagnosis of haemangiopericytoma on the basis of classically described specific signs. Instead of preserving the muscular environment, the surgical resection had to be extensive because of the poorly determined malignant potential of the tumour. PMID- 2221782 TI - [Three-dimensional imaging of the carpus]. AB - Since 1987, the authors have developed three-dimensional (3D) imaging of the carpus. This reconstruction based on 30 CT scans of the carpus is a new approach to imaging and allows spatial visualisation of the complex shapes of the carpal skeleton from all angles. The development of this technique should lead to a better understanding of the intimate physiology of the carpus and should allow the development of a real simulator of the wrist for precise planning of surgical procedures (osteotomy, intracarpal arthrodeses, etc.). It also helps to elucidate complex pathological images which are not always easy to interpret on CT scans. PMID- 2221783 TI - [Radiographic views in hand surgery]. AB - Numerous radiographic views are available for visualisation of the squeleton of the hand. After an analysis of the literature, the authors selected those approaches which are simple and yield the best results. PMID- 2221785 TI - [Current data on iron overload]. PMID- 2221784 TI - [MRI of acute myocardial infarction with injection of Gd-DOTA (15 patients)]. AB - We studied 15 patients 4 to 8 days after myocardial infarction by using ECG gated MR before and after administration of 0.2 mmol/kg Gd-DOTA. The diagnosis in each patient was confirmed by electrocardiographic criteria, elevated levels of fractionated creatine kinase (CK) isoenzyme, thallium scintigraphy, ventriculography and coronarography. T1-weighted, spin-echo images, were obtained before and immediately after injection of Gd-DOTA and were repeated 15 min later. The site of infarction was visualised in 10 patients as an area of high signal intensity after the injection of Gd-DOTA. Contrast between normal and infarcted myocardium was greatest 15 min after injection. Three patients were excluded because of failure to acquire adequate MR studies. In 2 other patients, the infarct were not detected. Before injection of Gd-DOTA, only 2 infarcts were detected. These results suggest that Gd-DOTA can improve MR visualisation and detection of acute myocardial infarction. PMID- 2221787 TI - [Synchronous and resectable hepatic metastases of colorectal cancer: should there be a minimum delay before hepatic resection?]. PMID- 2221786 TI - [Peroperative isotope detection]. PMID- 2221789 TI - [Hepatectomy with total vascular exclusion. Anatomical principles based on 64 dissections]. AB - Intra-operative hemorrhage is the main surgical risk during liver resections. Nowadays hepatectomies for large or posterior liver tumors close to the hepatocaval junction can benefit from total hepatic vascular exclusion (HVE) involving portal triad exclusion and clamping of the inferior vena cava (IVC) below and above the liver. Anatomical aspects of HVE have been studied in 64 subjects by segmental occlusive phlebographies of the IVC, injection of corrosive substances into the hepatocaval network, biometry of the retrohepatic IVC and serial sections of injected livers. A total HVE should exclude the right suprarenal and phrenic veins. Clamping of the suprahepatic IVC depends on the termination of the left inferior phrenic vein. Clamping of the subhepatic IVC must be retrohepatic: the right lobe of the liver has to be mobilized to free the right border of the retrohepatic IVC into which flows the right suprarenal vein 40 +/- 20 mm above the right renal vein and under the superior right hepatic vein. Both suprahepatic and retrohepatic clamps excluding the retrohepatic portion of the IVC (46.6 +/- 13 mm) and the hepatocaval junction should come in contact behind the IVC without overlapping. PMID- 2221788 TI - [Conservative surgery of splenic injuries in adults: trend or progress?]. PMID- 2221790 TI - [Obstruction of the common bile duct by a cystic duct cyst in the recipient after liver transplantation]. AB - Four cases of tension mucocele of the cystic duct of the graft after orthotopic liver transplantation have been described in the English literature. We report the case of a mucocele of the recipient's cystic duct occurring in a patient who underwent liver transplantation for sclerosing cholangitis secondary to histiocytosis X. At variance with the 4 previously reported cases, this complication could be related to progression of the initial disease in the recipient's cystic duct. To avoid such a biliary complication in patients undergoing a liver transplantation for sclerosing cholangitis, resection of the extra-hepatic duct must be as large as possible and choledochojejunostomy seems to be the best procedure for biliary reconstruction. PMID- 2221791 TI - [Early stomach cancer. Do not miss it!]. AB - It may be better to use the term of "superficial carcinoma" than "early gastric carcinoma". Out of 194 patients operated on for gastric carcinoma, 37 had a superficial carcinoma (19%). Seventeen had previously been treated for duodenal (n = 10) or gastric (n = 7) ulcer. Out of 23 barium meal examinations, 3 were normal. The macroscopic appearance at endoscopic examination was normal in 4 patients. In these cases the carcinoma was identified in biopsies. At laparotomy the gastric wall was normal in 16 patients. Gastric resection was subtotal (n = 28), total (n = 6), or partial (n = 1). The tumor was multifocal in 8 cases, and associated with intestinal metaplasia in 24 cases. The five-year actuarial survival rate was 77%. It is important to do not miss superficial carcinoma even in patient treated for peptic ulcer, and to perform biopsies even if endoscopic examination is normal. A subtotal gastrectomy may be performed with excellent results. PMID- 2221792 TI - [Factors influencing survival after resection of cancer of the cardia. Comparison of total esophagogastrectomy and upper pole esophagogastrectomy]. AB - Total oesophagogastrectomy (TOG) is the best surgical technique for carcinoma of the cardia. However, oesophagogastric anastomosis is easier in upper pole oesophagogastrectomy (UPOG). This is a retrospective study excluding post operative deaths and palliative surgery. We studied the factors affecting the survival and then compared TOG (n = 15) and UPOG (n = 26) in carcinomas of the cardia. Bad prognosis was related to several factors: poorly differentiated adenocarcinomas, tumor size, lymph node involvement and residual tumor at the resection margins. The survival rate of resected carcinomas of the cardia was 22 +/- 13%. No difference was noted between extended and limited resections. 5-year survival after UPOG was 20 + 18% and after TOG 11% (0-30) (p = 0.21). In stage 1B, 5-year survival after UPOG 11% and TOG was 50% (19-81) and 33% (0-82) (p = 0.54). In stages II and III A, 3-year survival after UPOG and TOG was 7% (0-20) and 0% (p = 0.16). For a given tumor size, 5-year survival is the same whatever the technique. PMID- 2221793 TI - [Perforation and rupture of the esophagus. Apropos of 35 cases]. AB - A series of 35 oesophageal perforations from the period 1980-1987 is reported. Sixteen perforations followed oesophageal endoscopy, 10 were spontaneous, 8 were due to foreign bodies and one was post-operative. The delay in reaching the right diagnosis was less than 24 hours in 18 cases and more than 24 hours in 17 cases. Oesophageal leak was demonstrated in 86% of our cases by contrast study; in the others by rigid oesophagoscopy. Perforation occurred in the cervical oesophagus in 6 patients, thoracic oesophagus in 28 and abdominal oesophagus in 2 (one had a double perforation). Three patients were managed non operatively and survived. Cervical oesophagostomy and oesophageal diversion were used in 4 patients as primary treatment because of perforation occurring in caustic burn cases (2 cases, both survived) or late severe sepsis (2 cases, both died). Two patients with neoplastic stricture were treated by oesophago-jejunal bypass without resection and partial oesophago-gastrectomy respectively: both survived. Direct suture and closure of the perforation were performed in 26 patients. Two died, one because of oesophageal leak. Post-operative localized leaks developed in 5 other patients without any mortality and 4 healed with conservative management. The overall mortality rate was 11% (4 patients). All had a delayed diagnosis (more than 48 hours). We suggest that even in patients with delayed diagnosis of a non-malignant oesophageal perforation, direct suture and closure should be attempted under protection of functional oesophageal diversion and "contact drainage" to canalize a possible post-operative localized leak. Good oesophageal diversion can be achieved by naso-oesophageal suction and gastric suction through gastrostomy or with oesogastric antireflux procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221794 TI - [What is the value of tracheobronchial fibroscopy in the assessment of esophageal cancer?]. AB - The aim of this study is to evaluate the role of bronchoscopy in the assessment of resectability of esophageal carcinomas. From 1981 to 1986, 125 patients were referred for a carcinoma of the esophagus. Bronchoscopy was performed in 105 cases. Patients were classified into 3 groups: group I: normal bronchoscopy (58 cases: 55.2%); group II: compression, localized inflammation (35 cases: 33.3%); Group III: invasion (12 cases: 11.5%). Tracheo-bronchial abnormalities were found whatever the site of the esophageal carcinoma: 60% of cases for the upper third, 40% for the middle third and 36% for the lower third. They were significantly more frequent when the esophageal tumor was larger than 5 centimeters. Correlation with CT scan was good in 75% of cases. Sensitivity and specificity of these two exams were similar and they appeared to be complementary. In group I, resection was impossible or palliative for bronchial reasons in 10% of cases, while resection was impossible or palliative in 35% of cases in group II. Lastly, resection was curative in 73.5% of cases in group I and in only 39% of cases in group II. Bronchoscopy must be systematically performed in carcinoma of esophagus. It may predict the palliative nature of resection if abnormalities are present, and may contraindicate the resection when invasion of the bronchial tree is discovered. PMID- 2221796 TI - [Pancreatic pseudotumor caused by isolated tuberculous retro-duodenopancreatic adenopathy. Apropos of a case]. AB - The authors report the case of 32 year old woman with tuberculous lymph nodes of the common bile duct which simulated a tumor of the head of the pancreas. Despite modern radiological investigation (US, CT scan, IRM, US with aspiration biopsy), laparotomy was necessary to establish the diagnosis and to perform simple drainage. PMID- 2221795 TI - [Gastric esophagoplasty in the treatment of cancer of the esophagus]. AB - Between March 1982 and December 1987, 112 patients with oesophageal cancer were treated by gastroplasty following oesophagectomy to restore gastrointestinal continuity. This technique was used in all oesophageal cancers regardless of their site, with the exception of paryngo-oesophageal and oesophago-cardio-fundal cancers. The overall mortality of 12.5% fell to below 6% during the last two years. The postoperative course was straightforward in 54.5% of cases. The most frequent complications were respiratory tract complications (19 cases of ARDS out of 112 patients, i.e. 17%) and fistulae at the oesophago-gastric anastomosis (9 cases out of 112, i.e. 8%). The secondary complications were dominated by anastomotic stenoses (19/98, i.e. 19.3%). PMID- 2221797 TI - Differentiated thyroid cancer: outcome of treatment in 80 cases. AB - The author carried out a retrospective analysis, with 6-13 years follow up, of 80 patients with differentiated thyroid cancer. The patients were treated with surgery, radioactive iodine, radiation therapy and suppression hormone therapy. The results, 5 year and 12 year survivals of 97% and 85%, are comparable with the results of much larger series with longer periods of follow up. The most significant prognostic factor was age at presentation. No patient below the age of 45 died from the cancer even if, at presentation, there was very advanced local disease or multiple distant metastases. In addition, sex, extent of local disease and presence of multiple metastases were also important in predicting survival. Cervical node involvement, by itself, did not worsen the prognosis and long survival with lung secondaries is possible. PMID- 2221798 TI - A study of non-toxic goitre. AB - A population study showed a prevalence of 2.8% for nontoxic goitres. The clinical significance of non-toxic goitres were not previously defined. This study examined 64 patients with non-toxic goitres which were classified clinically as diffuse (gp1), lobular (gp2) and nodular (gp3). They were studied in terms of thyroid antibodies, radioisotope scanning, ultrasonography and fine-needle aspiration cytology. The goitres were mainly nodular (69%), the rest were diffuse and lobular in equal numbers. Seventy percent of the nodular goitres had 1 nodule. One case of diffuse goitre and half the lobular goitres had multinodularity demonstrated on imaging. Antithyroid antibodies were detected in 20% of gp2, 7% of gp3 and none in gp1. Malignancy was found in 2% of gp2, 11% of gp3 and nil in gp1. A management strategy for non-toxic goitre was discussed. PMID- 2221799 TI - Humoral immune abnormalities in diabetes mellitus. AB - We previously showed that for Singapore diabetics, a low prevalence of islet cell antibodies (ICA) and insulin autoantibodies (IAA) were observed, unlike the high prevalence rates in Caucasian populations. In this report, we have measured other autoimmune markers (thyroid autoantibodies, thyrotrophin [TSH] receptor antibodies, rheumatoid factor and anti-dsDNA antibodies) to assess the extent of autoimmunity in our newly diagnosed diabetes patients and those with long standing diabetes. Results indicate that there is a raised prevalence of thyroid autoantibodies in diabetics compared to the general population. Thyroid autoantibodies occurred in 24.3% (28/115) of the patients; thyroid microsomal antibodies (16.5%, 19/115) was much higher than for thyroglobulin antibodies (1.7%, 2/115). Prevalence rates of thyroid autoantibodies were lower in diabetics who were newly diagnosed (21.6%, 11/51), compared to those with long-standing disease (25.5%, 14/55). Three patients (3/9) with gestational diabetes were also positive for thyroid autoantibodies. TSH receptor antibodies associated with Graves' disease, were found in two patients. However, they also had thyrotoxicosis. Five patients (4.3%, 5/115) were detected with rheumatoid factor, but were clinically asymptomatic. Anti-dsDNA antibodies were not detected in any of the subjects. The presentation of thyroid autoantibodies or rheumatoid factor with age did not coincide with diabetes-associated ICA and IAA. It may mean that inspite of prevalence of subclinical autoimmunity in diabetes, autoimmunity against beta-cell lesions is not associated with the overall autoimmune tendency in our diabetes. PMID- 2221800 TI - The pattern of diabetes in a primary health care setting in Singapore. AB - This is a study of Diabetes mellitus and its treatment in a single doctor government primary health care clinic in Singapore. Data was collected on the entire 349 patients with diabetes attending this clinic over a three month period in 1987. We found there was an increasing number of diabetics with age and a substantial proportion was above 70 years of age. Only 7% had their diabetes treated with diet alone and 9.6% were treated with insulin. Most (61%) patients were on tolbutamide, with 17.6% on glibenclamide and 5.9% on chlorpropamide. Hypertension was found in 38% of the diabetic patients but was not associated with increase in age of the patient. The duration of diabetes, but not the age of the patient, was positively associated with the number of drugs taken by the patient (chi-squared, p less than 0.05). PMID- 2221801 TI - Oral glucose tolerance test--can the reflectance meter replace laboratory-based methods? AB - Sixteen national servicemen detected to have glycosuria on routine medical examination were subjected to 3 successive oral glucose tolerance tests. Capillary blood glucose was measured by reflectance meter in the first test (oGTT1), venous whole blood glucose by Beckman Synchron CX3 Analyser in the second (oGTT2) and by both methods in the third (oGTT3). In oGTT1, 1 subject was classified as diabetic and 15 as Impaired Glucose Tolerance (IGT). In oGTT3, using capillary blood glucose, 1 was diabetic, 8 IGT and 7 normal. Using venous whole blood, in oGTT2, 1 was diabetic, 3 IGT and 12 normal as compared to 1 diabetic, 4 IGT and 11 normal in oGTT3. There is considerable variation in classification as a result of using capillary blood glucose measured by reflectance meter as compared to the laboratory-based method. Capillary blood glucose measurement for oral glucose tolerance test cannot be recommended. PMID- 2221803 TI - Management and outcome of gestational diabetes in Alexandra Hospital, Singapore. AB - We analysed 216 patients with gestational diabetes over a 3 year period. These patients were managed by a diabetic team under a standardised protocol. Forty percent of these patients required insulin therapy. The incidence of pregnancy hypertension was 14.4%, macrosomia 8.8% and major congenital malformation 3.7%. The Caesarean Section rate was 34% and the overall Perinatal Mortality Rate was 1.9%. However, neonatal morbidity rate remained high--44% of infants have had one neonatal complication and 17.6% had 2 or more complications. Pregnancy outcome was further analysed among patients with different degrees of glucose intolerance at diagnosis. We noted that both macrosomic rate, neonatal morbidity rate, as well as proportion of patients requiring insulin were higher in the group with a higher degree of glucose intolerance. There was, however, no difference in incidence of hypertension or hydramnios in the different subgroups. PMID- 2221802 TI - Effects of low dose guar in non-insulin dependent diabetic patients. AB - Thirteen non-obese, non-insulin-dependent diabetic patients were given guar granulate in an average dose of 7.1 grams daily for 8 weeks. The mean fructosamine fell from 3.3 +/- 0.69 mmol/L (p less than 0.01). Mean glycosylated haemoglobin (HbA1c) fell from 8.17 +/- 2.2% preguar to 7.67 +/- 1.81% (1 = ns) and to 7.39 +/- 1.23% (p = ns) at 8 weeks and 12 weeks postguar respectively. Eight weeks after the discontinuation of guar fructosamine rose to 3.61 +/- 0.95 mmol/L (p less than 0.05) while HbA1c rose to 8.23 +/- 2.08% (p = 0.05). There were no significant changes in fasting blood glucose, lipids, and body weight. Mild gastrointestinal side-effects occurred in 11 patients during the treatment with guar. It is concluded that daily ingestion of low dose guar modestly improves glycaemic control, such improvement dissipating by 8 weeks following cessation of its use. PMID- 2221804 TI - The value of C-peptide level measurements in diabetes mellitus. AB - A prospective study of 27 patients with diabetes mellitus was done to assess their basal and glucagon stimulated C-peptide levels. Based on recommended cut off values for both basal and stimulated C-peptide levels, these patients were subsequently classified as insulin or non-insulin requiring diabetics. As in most other studies, we demonstrated a good correlation between the basal and glucagon stimulated C-peptide levels. Of the 8 patients on insulin therapy prior to this test, we found that only 2 actually required insulin i.e. had poor pancreatic reserve. Of the remaining 19 patients who were on diet and/or oral hypoglycaemic agents, we found that only one newly diagnosed diabetic had a definitive indication for insulin therapy. Among the other diabetics with poor control despite being on oral hypoglycaemic therapy, we found they had good islet cell secretory capacity for insulin. PMID- 2221806 TI - An amperometric measurement--the ExacTech pen meter. AB - A new device based on amperometric measurement is currently available for diabetic patients to perform blood glucose tests for self-monitoring. The meter (Exac TechR) which comes configured as a pen, is extremely simple to use. It takes only 30 seconds for a blood glucose reading to be determined and virtually eliminates user errors commonly associated with colour reagent test-strips. An assessment of the technical aspects--precision and accuracy, was carried out in comparison with a reference analyser. Analysis of 174 venous blood samples (range 26-412mg/dl) indicated that ExacTechR gave acceptable accuracy for values greater than 151mg/dl but less accurate at less than 150mg/dl. Precision, assessed with seven glucose concentrations (52-300mg/dl), gave an average CV of 4.3% (2.6 5.2%). Data obtained from two other ExacTechR meters demonstrated similar precisions. Anticoagulants affected ExacTechR measurements. Compared to plain blood, blood glucose measurements with the ExacTechR using fluoride-oxalate, EDTA and heparinised blood, showed a mean deviation of +22%, -4% and -1.9% respectively. PMID- 2221807 TI - Serum fructosamine concentrations in Singapore pregnant women. AB - Serum fructosamine levels in women at pregnancy (28 weeks' gestation) were determined. The women (n = 99) also participated in an oral glucose tolerance test (OGTT) with a 75g liquid glucose load, to determine their glucose tolerance. At 32 weeks' gestation, seventy-nine of them repeated the oral glucose tolerance test and fructosamine measurement. Results showed that fructosamine levels in pregnant women with normal glucose tolerance (2.20 +/- 0.19 mmol/l, n = 76), were not statistically different from those with glucose intolerance (gestational diabetes: 2.19 +/- 0.22 mmol/l, n = 23) at 28 weeks' and also 32 weeks' gestation. However, serum fructosamine levels in pregnant women were lower than those in non-pregnant subjects. Serum fructosamine measurement is not a sufficiently sensitive test for diagnosis of gestational diabetes. PMID- 2221805 TI - Home glucose monitoring in management of diabetes in pregnancy in Singapore. AB - The incidence for diabetes in pregnancy for 10,941 deliveries in the department over a 3 1/2 year period is 5.04% (551 patients). Of these, 33.2% (183 patients), were recruited for home glucose monitoring programme. The gestational diabetics form 76.3%, while pregestational diabetics form 23.7% of the patients. The total period of hospitalisation was less than 4 weeks in 89.4% of patients. The corrected (excluding those with birthweight of less than 1000 G) perinatal mortality rate was 5.78 per 1000. PMID- 2221808 TI - Diabetic retinopathy--results of a two year screening programme in two medical units in Singapore. AB - Three hundred patients with Diabetes Mellitus from 2 medical units in Singapore were screened for retinopathy over a 24 month period. Prevalence of retinopathy in this population was 38% with sight-threatening retinopathy in 17%. Risk factors associated with retinopathy included a longer duration of disease, the presence of hypertension, nephropathy and poor glycaemic control. Prevalence of retinopathy was higher in females. Malays and Indians had higher prevalence of retinopathy than Chinese. PMID- 2221809 TI - Epidemiology of diabetes mellitus in the Asia-Pacific region. AB - The complex interaction between genetic and environmental factors in the causation of diabetes mellitus is well illustrated by the epidemiology of diabetes in the Asia-Pacific region. Among the Chinese, the prevalence of diabetes is uniformly higher among Chinese living outside China than in the Chinese in The People's Republic of China. Similarly among the Indians, the prevalence of diabetes is universally higher in those who have settled outside India than in Indians in India. In the Pacific populations, diabetes is much commoner among the Nauruans and Fiji Indians. Throughout the Asia-Pacific countries, economic progress and urbanisation have a uniformly deleterious effect on diabetes. A better understanding of the hereditary and environmental factors in the causation of diabetes is required to halt and reverse the rising prevalence of diabetes in the Asia-Pacific region. PMID- 2221810 TI - Pathogenesis of type 1 and type 2 diabetes mellitus. AB - The majority of patients with diabetes mellitus can be classified as suffering from either Type 1 or Type 2 diabetes. The pathogenetic pathways for these two categories of diabetes appear to be distinct and separate. Both forms of diabetes have a genetic as well as environmental component in their pathogenesis. Type 1 diabetes has a weaker genetic link; its association with HLA antigens is well established. Type 2 diabetes has a stronger genetic association but the exact gene or genes responsible is unknown. The environmental trigger in Type 1 diabetes may be a viral infection while urbanisation, obesity, physical inactivity and stress may trigger the development of Type 2 diabetes. Type 1 diabetes is a chronic autoimmune disease where beta cell destruction may occur over a number of years before clinical diabetes is diagnosed. Type 2 diabetes is the result of an interplay of relative insulin deficiency or a defect in insulin release together with insulin resistance. Hyperglycaemia perpetuates the problem of beta cell defect and insulin resistance. The understanding of pathogenesis of diabetes is the key to prevention and treatment of diabetes mellitus. PMID- 2221811 TI - Diabetes education: the Singapore experience. AB - Diabetes Mellitus is one of the world's major health problems in the developed and developing countries. With increasing industrialization and urbanisation, there is an increasing frequency of diabetes in every decade. PMID- 2221812 TI - Diabetes mellitus and its chronic complications in Singapore: an increasing healthcare problem. AB - We studied the prevalence of diabetes mellitus in Singapore and compared it to the study conducted ten years previously. A rise in prevalence rates from 2.0% to 4.7% was demonstrated. Impaired glucose tolerance (IGT) was studied for the first time, and a prevalence rate of 0.9% was found. Findings on chronic complications of diabetes were also reported. A high frequency of coronary heart disease and hypertension were detected in both diabetic and IGT subjects. Obesity and hyperlipidaemia were identified as important risk factors. This study demonstrates the scope and impact of diabetes mellitus as a major healthcare problem in Singapore. Strategies directed at prevention and control of this disease needs to be implemented so as to check its rising trend. PMID- 2221814 TI - The use of luteinising hormone releasing hormone and its analogues for induction of ovulation and ovarian stimulation for in-vitro fertilisation. AB - The use of subcutaneous pulsatile luteinising hormone releasing hormone (LHRH) for induction of ovulation in patients with hypogonadotrophic hypogonadism is efficacious and safer compared to human menopausal gonadotrophin (hMG) because of the lower risk of ovarian hyperstimulation and multiple pregnancy. In clomiphene citrate (CC) nonresponsive cases of polycystic ovarian disease (PCOD), the major advantage of pulsatile LHRH is that when ovulation occurs, it is usually uni follicular. In cases of PCOD, we have found that if pulsatile LHRH alone fails to induce ovulation, addition of clomiphene citrate or a small dose of follicle stimulating hormone (FSH) will augment its action and allow, in the majority of cases, the threshold of stimulation to be reached that would be sufficient to induce ovulation but not produce clinical hyperstimulation or multiple pregnancy. LHRH analogues to desensitise the pituitary prior to ovarian stimulation with hMG have been recently used in in-vitro fertilisation (IVF). We have compared the use of the LHRH analogue, buserelin (Hoechst, UK) + hMG with clomiphene + hMG for ovarian stimulation in IVF in a number of prospective studies. In this review, the role of pituitary desensitisation in IVF is discussed in the light of our results. We have found that although the mean number of oocytes, the implantation rate and pregnancy rate per embryo transfer are higher in patients who receive buserelin + hMG, the differences are not statistically significant. The length of time taken to achieve pituitary desensitisation is increased in patients who have PCOD or who form ovarian cysts in response to the administration of buserelin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221813 TI - The gonadotrophin surge in humans: its mechanism and role in ovulatory function- a review. AB - The presence of the positive feedback by oestrogen resulting in the mid-cycle gonadotrophin surge in women distinguishes the female's feedback control of gonadotrophin secretion from that in males. The gonadotrophin surge is an event crucial for final oocyte maturation, ovulation and subsequently for corpus luteum function. In this article, the roles of oestrogen, progesterone and testosterone in the regulation of the gonadotrophin surge are reviewed. Evidences appear to support the suggestion that an oestradiol pulse of sufficient potency and lasting for an adequately long duration alone is sufficient to trigger off the LH surge. Progesterone has a biphasic effect on LH secretion, and although not required for the initiation of the LH surge, may play a role in maintaining the LH peak. Testosterone, on the other hand, does not modulate the LH surge mechanism in man. Dysfunction of the gonadotrophin surge mechanism may account for some forms of ovulatory disorders: amenorrhoea and in some cases of delayed or precocious puberty. In patients with polycystic ovary syndrome (PCOS), different degrees of dysfunction of the gonadotrophin surge mechanism have been shown. PMID- 2221815 TI - Persistent hypomagnesaemia following parathyroid surgery, hypermagnesuria as a possible cause. AB - A patient who had prolonged hyperparathyroidism with extensive bone involvement developed delayed post-surgical complications of pseudogout and the hungry bone syndrome with persistent hypocalcaemia and hypomagnesaemia. Although urinary calcium excretion was appropriate for the hypocalcaemia, there was severe excessive renal loss of magnesium despite the hypomagnesaemia. Renal magnesium excretion returned to normal only after correction of the hypocalcaemia. Hypermagnesuria may be an important cause of resistant hypomagnesaemia after parathyroid surgery. PMID- 2221816 TI - Non-functioning cyst of the adrenal gland--a case report. AB - Adrenal cysts are a rare entity. Only about 300 cases have been reported throughout the world. A case of an asymptomatic, benign, non-functioning adrenal cyst of the left adrenal gland is presented. Pre-operative diagnosis is usually by incidental imaging findings as the majority of adrenal cysts are asymptomatic. The adrenal cyst in this case was detected on an abdominal ultrasound for the investigation of jaundice, and confirmed by a CT scan examination. Selective biochemical studies are needed to assess adrenal function, and here they were normal. Simple surgical enucleation of the cyst, with preservation of remaining adrenal tissue is the treatment of choice. PMID- 2221817 TI - A Chinese family with Wolfram syndrome presenting with rapidly progressing diabetic retinopathy and renal failure. AB - We describe a Chinese family with three siblings, all females, presenting with the Wolfram Syndrome. All three cases had almost similar clinical presentation of insulin-dependent diabetes mellitus, with rapid development of severe renal and retinal complications. Two siblings died at age thirty and thirty-one years of end-stage renal failure. All three cases had visual symptoms since early childhood progressing rapidly to loss of vision. Two of the three siblings had severe diabetic retinopathy requiring laser photocoagulation. These presentations are in contrast to most reported cases of the Wolfram syndrome where advanced diabetic eye complication is a rare feature. We also present several features present in one of the siblings, viz., microcephaly, microstomia, clinodactylyl, brachydactylyl, empty sella syndrome and severe hypoplasia of the right internal carotid vessels associated with mild narrowing of the left internal carotid artery which have not been previously described. PMID- 2221818 TI - [18-Hydroxycorticosterone, 18-hydroxydesoxycorticosterone. Why, when, how to determine plasma levels in some adrenal pathologies]. AB - The authors review some current ideas concerning the role of 18-hydroxylated corticosteroids as mineralocorticoids themselves and as possible precursors of the principal mineralocorticoid, aldosterone. In particular, the physiological and pharmacological agents affecting their secretion are discussed together with a description of the methods used for their analysis in plasma in the department of Clinical Biochemistry Pitie-Salpetriere. Finally, the value of these assays in the differential diagnosis of mineralocorticoid hypertension and inborn errors of corticosteroid biosynthesis is assessed and the constraints on sampling technique listed. PMID- 2221819 TI - [Stress and immunity. The role of stress in auto-immunity of Basedow's disease]. AB - The possible influence of stress on the immune system, long since suspected by the clinicians in their daily practice, was confirmed by human and animal studies, some of which being recent. Stress generally exert an immunosuppressive effect, but some of its characteristics (nature, duration, intensity, controllability of the stressing situation) can modulate this response, amplifying or reversing it. The concerned mechanisms are complex, involving the autonomic nervous system, the hypothalamo-pituitary complex and its target-glands through hormonal receptors born on immunocompetent cells. The immune system, conversely, is able to inform the brain about the interference of non cognitive stimuli (viruses, bacteria, tumors) through immunologic cell-derived immunohormones active in the central nervous system. Thus, close immune neuroendocrine interactions exist, in order to cope with stress of all kinds. The stress can act in Graves' disease by depressing the T suppressive function via the hypothalamo-pituitary-adrenal axis, by eliciting the secretion of catecholamines capable of initiating an hyperthyroidism, by facilitating through its immunosuppressive action a viral infection that can have a part in initiating the auto-immune process. PMID- 2221820 TI - [Induction of ovulation, with pulsatile GnRH by subcutaneous route in amenorrhea of hypothalamic origin]. AB - Twelve patients affected by secondary amenorrhea of hypothalamic origin, resistant to Clomiphene Citrate treatment, were treated for 2 consecutive cycles with subcutaneous pulsatile administration (s.c.) of Gn-RH by computerized portable pump (Ziklomat-Ferring) at a dose of 20 mcg every 60-90 minutes for a total of 20 cycles. On the average 85% of ovulatory cycles and 30% of pregnancies per cycle were obtained with this therapy. The number of ovulatory cycles and pregnancies obtained in the second cycle of treatment were in percentage higher, with respect to the first cycle of treatment. Only one subject, not responsive to both cycles of s.c. administration, underwent an intravenous therapy with positive results. PMID- 2221821 TI - [Familial primary empty sella turcica. Apropos of a family with 3 cases]. AB - Three members of a family, the father and two children, present a primary empty sella. The only clinical symptom is headache. The ophthalmologic examen, and the pituitary function are quite normal. No other anomaly is associated. This type of cases has never been published. PMID- 2221822 TI - [Dysthyroidism and Parkinson's disease]. AB - Associations between hyperthyroidism and Parkinson disease have been reported. The treatment of the hyperthyroid state seems to improve the extrapyramidal symptomatology. We report a case of a woman suffering from Parkinson disease and hypothyroidism. The treatment with thyroxine increased parkinsonian tremor. Dopamine regulation of TSH circadian and pulsatile release is not clear. These observations stress the possible role of thyroid hormones in regulating dopaminergic metabolism. PMID- 2221823 TI - Use of DNA amplification (PCR) and direct DNA sequencing in the characterization of C4 alleles. AB - A procedure for detailed characterization of individual C4 alleles has been developed. DNA containing the two polymorphic clusters of C4 was amplified in the polymerase chain reaction (PCR). Direct DNA sequencing of amplified DNA was then performed by a modification of previously described techniques. The results were confirmed by M13 sequencing. Single C4A3 and C4B1 allele sequences were in accordance with previous reports. An individual typed C4A3B1 revealed double bands in the autoradiogram in the positions corresponding to the polymorphic nucleotides. We did not find the reported thymine in position 3641 specific for the C4A4 allele in an individual typed C4A4B2. PMID- 2221824 TI - Assignment of the human nicotinic acetylcholine receptor genes: the alpha and delta subunit genes to chromosome 2 and the beta subunit gene to chromosome 17. AB - The chromosomal assignments of the genes coding for the alpha, beta and delta subunits of the human nicotinic acetylcholine receptor have been determined from a panel of somatic cell hybrids and by direct in situ hybridization. The results localize CHRNA to 2q24-2q32. CHRNB to 17p11-17p12, and CHRND to chromosome 2q33 2qter. PMID- 2221825 TI - A cytogenetic and molecular reappraisal of a series of patients with Turner's syndrome. AB - The results of a cytogenetic and molecular reinvestigation of a series of 52 patients with Turner's syndrome are reported. No evidence of Y chromosome material was found among the patients with a 45,X constitution but two patients were found to have a cell line with a r(Y) chromosome which was previously thought to be a r(X). The parental origin of the single X in the 45,X patients was maternal in 69% and paternal in 31%, a similar ratio to that seen among spontaneously aborted 45,X conceptuses. This suggests that X-chromosome imprinting is not responsible for the two grossly different phenotypes associated with a 45,X chromosome constitution. Approximately half of the structurally abnormal X chromosomes were maternal in origin and half paternal. This observation is consistent with either a meiotic or post-zygotic mitotic origin and at variance with the predominantly paternal origin reported for autosome structural abnormalities. PMID- 2221826 TI - Standard maps of chromosome 10. AB - To achieve consensus more exact definitions of genetical maps are required, of which standard, comprehensive and skeletal might be some. A standard genetic map gives distance from pter in centimorgans (cM), uses the international nomenclature for assigned loci, is sex-specific, and allows as well as possible for interference and typing errors. A standard physical map gives distance from pter in megabases (Mb). A standard map is called comprehensive if it aims to include all syntenic loci, and skeletal if it is limited to loci whose order is well supported. Loci with established order are called skeletal, and are used to define regional assignments of other loci. These principles are illustrated using the CEPH data for chromosome 10. Map lengths by multiple 2-point analysis under supported interference are in good agreement with other evidence, but multipoint mapping gives a substantial overestimate. There are currently 21 loci in the skeletal genetic map and 40 loci in the comprehensive genetic map. From these data, cytogenetic assignments, and partial genetic maps the physical location has been estimated for 85 loci. MEN2A is in a region close to the centromere in which male recombination per megabase is much reduced. Order of DNA markers in this densely mapped region has not been determined, and therefore the exact location of MEN2A is uncertain, although it is likely to lie between D10S34 and D10S30 and close to D10S11. PMID- 2221827 TI - The linkage detection problem. AB - Linkage data in man are usually analysed on families lacking a full set of grandparents on the assumption that there is one locus relating to an abnormal phenotype, the test locus. The basic problems of establishing linkage of this locus to another locus, the marker locus, with a defined likelihood and of estimating the recombination fraction were resolved by Morton (1955). However, the likelihood ratio derived after estimating the most likely recombination fraction is widely misunderstood to be a direct measure of the likelihood of linkage while the bias of estimates conditional on some likelihood criterion derived from the same data is usually ignored. Since data are limited this tolerance of excessive confidence in detecting linkages and a consistent tendency to underestimate recombination fractions is justified but the expected errors are not small and they are readily magnified when multiple loci are involved. Multiple markers provide further opportunities for detecting false linkages although the corrections required are known. The problems imposed by multiple loci at which mutations lead to a common phenotype have so far had little consideration. As most proteins are multimers whose units are not necessarily coded for by neighbouring loci, and as disturbances to any of several enzymes acting in series may lead to similar consequences, the assumption of a one-to-one relationship between a locus and a phenotype will usually be wrong. PMID- 2221829 TI - [Autosomal dominant polycystic kidney in adults and transplantation]. AB - Seventy-six patients with polycystic kidneys were followed in the Bicetre renal transplantation unit. Fifty four were transplanted. Fifty two nephrectomies were performed in these patients essentially because of the size of the kidney and for renal infections. Fifty four patients were transplanted at a mean of 44 years. The actuarial survival of the patients at one year and at three years was 92% and 88% and the actuarial survival of the grafts at one year and at five years was 87% and 71%. These results are comparable to those obtained in other patients transplanted in the unit. Pre-transplantation nephrectomy and the patient's age do not aggravate the prognosis. Nephrectomy may be justified in these patients when they must be transplanted as transplantation currently gives very good results. PMID- 2221828 TI - [Autosomal dominant polycystic kidney in adults]. AB - The authors present a general review of autosomal dominant transmission of polycystic kidneys. It represents 10% of all causes for haemodialysis. Its penetrance is close to 100%. The dominant aetiology at the present time is obstruction due to hyperplasia of the tubular epithelium which induces cystic dilatation which extends to involve all of the nephron. The cysts are cortical and medullary. The diagnosis is based on an association of enlarged kidney and a family history. The commonest associated abnormalities are hepatic cysts in 60% of cases, cerebral aneurysms in 10 to 20% of cases and colonic diverticulosis in 80% of cases. At the stage of renal failure, patients must be treated for hypertension and deterioration in nephron function must be prevented by a low protein diet. When the patient reaches the stage of renal failure and must be dialysed, he must be rapidly enrolled in a transplantation programme as the actuarial graft survival is more than 80% at 1 year and more than 70% at 5 years. PMID- 2221830 TI - [Percutaneous nephrostomy in the treatment of pyonephrosis. A comparative study apropos of 36 cases]. AB - This study is a comparison of the treatments used in 36 patients suffering from pyonephrosis. The patients were subdivided in two groups: cases having undergone previous percutaneous drainage; and cases having undergone primary nephrectomy. These latter cases presented a high complication rate. We believe that preliminary drainage by percutaneous nephrostomy, constitutes the procedure of choice, when ever possible, to drain the kidney and prepare the patient for nephrectomy. PMID- 2221831 TI - [Endo-urology in diseases of the upper urinary tract other than tumors and calculi]. AB - Thirty-three patients underwent percutaneous treatment for upper urinary obstructive disease in our Institute. Cold-knife incision of 16 cases of uretero pelvic junction obstruction and 4 cases of infundibular stenosis was performed. Balloon dilatation of the caliceal neck was performed in 1 patient with caliceal diverticulum. In 4 of the patients treatment failed requiring open surgical correction. Thirteen patients presented iatrogenic ureteral obstruction: balloon dilatations or cold-knife incisions were performed. Four of the 9 patients evaluable obtained significant benefit from the endourological treatment. Endopyelotomies for UPJ obstruction seem effective and reduce morbidity and operating times. Ureteral obstructions appear less responsive to the endo urological approach. Definitive conclusions concerning the effectiveness of these procedures requires larger series of patients and longer follow-up. PMID- 2221832 TI - [Current status of urethral stenosis in tropical Africa/ Apropos of 71 cases]. AB - In this study of seventy-one cases, the authors report the characteristics of the clinical course and treatment of urethral stricture in tropical Africa. In this special context, only 38% cases could benefit from a curative procedure on the urethra, whereas in 43.6% of patients, local complications only allowed palliative treatment (periodic dilatation of urethra, perineal uretherostomy or definitive cystostomy). PMID- 2221833 TI - [Obstructive anuria in children. Apropos of 22 cases]. AB - The authors report twenty two cases of obstructive anuria observed in children. Causes are diverse: 6 cases were observed during the course of tumors, 4 cases were secondary to bilateral renal stones (or unilateral in a single kidney), 3 cases were observed before surgical correction of latent or well tolerated congenital uropathy, and 9 cases in the immediate postoperative period (including 8 after antireflux surgery). In the emergency situation, treatment of obstructive anuria is based on urinary diversion ideally by percutaneous nephrostomy under ultrasonic control. But prevention is the best treatment of anuria: treatment of urinary tract infections resulting in renal stones, in case of tumor, ultrasonographic survey of chronic upper tract dilatation: rigorous atraumatic operative technique avoiding any oedema. PMID- 2221835 TI - [Results of the surgical treatment of impotence due to venous leakage by insertion of a prosthetic venous tourniquet. 26 patients reviewed with a 1-year follow-up]. AB - Twenty-six patients have been operated by pericavernoplasty with a band of synthetic material. After 1 year, 61.6% had a good result. Venous leaking is certainly a disease of the corpora cavernosa. PMID- 2221834 TI - [Varicocele in childhood and adolescence. Evaluation apropos of a series of 58 cases]. AB - 5 to 25% of the male adolescents present with a varicocele; only those cases inducing serious discomfort or affecting the development of the testis require surgical treatment. Nevertheless the results of surgery are disappointing with a high recurrence rate. Based on a better knowledge of the testicular venous drainage, it appears that the conventional high ligation of the spermatic vein(s) might not be sufficient to cure the varicocele, fifty-eight patients were operated upon using four different procedures. Only a complete and proximal ligation of all of the visibly dilated veins seems to prevent recurrences with a follow-up of at least one year. However, out of eleven cases treated with this original procedure, one patient, already operated upon twice without success, developed secondary atrophy. PMID- 2221836 TI - [Fracture of the corpus cavernosa. Apropos of 67 cases]. AB - The authors report a series of sixty-seven cases of fracture of the corpus cavernosa, 2 of which were associated with partial rupture of the urethra. Most of the fractures (61 cases) were due to a deliberate manipulation of the erect penis. A coital "faux pas" was only reported in 6 cases. Early surgical treatment, drainage of the haematoma and suture of the corpus cavernosa prevented cicatricial fibrosis, curvature of the penis and distal flaccidity interfering with erection. PMID- 2221837 TI - [Exclusive piezoelectric lithotripsy in the treatment of calculi larger than 30 mm (partial or complete coralliform, pyelic calculi)]. AB - Thirty patients with partial or total staghorn stones or calculi larger than 30 mm were treated by piezoelectric lithotripsy (PEL) monotherapy using an EDAP LT 01 lithotripter with ultrasound guidance. Nineteen of these patients had pelvic stones; the other 11 had partial (9) or total (2) staghorn stones. All patients first underwent an initial lithotripsy session. No anesthesia or IV sedation was required in any case. If stone fragmentation was achieved during this first session, a double-J stent was inserted before the second lithotripsy session. Prior to the first session, 18 of 30 patients had sterile urine cultures; 12 of 30 presented major distension of the excretory tract. Results were analyzed to determine the factors influencing the outcome of this therapy. Three months after the first session, patients were considered cured if their stones had completely disappeared according to plain abdominal films (14 of 30, 46%). In seven patients (23.3%) fragmentation had occurred but residual fragments remained (1 to 3 fragments less than or equal to 4 mm). No fragmentation was obtained after the first session in nine patients (30.7%) (1 total staghorn stone, 8 pelvic stones). The mean number of treatment sessions was five (range, 1 to 15). Complications occurred in only 10% of patients (3 of 30): two steinstrassen and one acute pyelonephritis. Eighty-three percent of patients without major excretory tract distension and 55% of patients whose initial urine culture was sterile achieved a stone-free state. Therefore the best indications for PEL monotherapy for calculi larger than 30 mm are pelvic stones and partial staghorn stones and no major excretory tract dilatation in patients with sterile initial urine cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221838 TI - [Emphysematous pyelonephritis. Apropos of a case]. AB - Emphysematous pyelonephritis is a rare form of pyelonephritis that carries a very poor prognosis. This article reports a review of the literature on this condition and describes the clinical and roentgenographic criteria for diagnosis. Diagnosis rests on the presence of clinical manifestations of pyelonephritis with intrarenal air-filled images on the roentgenograms. Both the author's personal experience and the data from the literature confirm the need for urgent treatment combining antimicrobial agents effective against Escherichia coli, the most common causative agent, and surgery, which usually consists in a nephrectomy. PMID- 2221839 TI - [Treatment using an endo-urologic approach of stenoses following uretero intestinal anastomosis]. AB - Twenty-one strictures following uretero-digestive anastomoses were treated by percutaneous transrenal dilatation. In 20 cases, an Olbert type angioplasty balloon on a guidewire was used. Rigid coaxial dilators were used in one patient after failure of the preceding technique and an electroincision was performed prior to dilatation in the remaining case. Overall, percutaneous transrenal dilatation was successful in nine patients, whereas ten dilatations failed and two patients are undergoing continued modeling with a mean follow-up of 16 months (range 1-42 months). Success rates by type of anastomosis were as follows: Bricker 5/12; Coffey 1/4; enterocystoplasty 2/4 and ureteroileovesical anastomosis 1/1. The date of development of the stricture, duration of modeling, and caliber of the indwelling catheter were apparently without influence on results. Because morbidity is low with percutaneous transrenal dilatation, this technique is advocated as first-line treatment, with surgery being reserved to failures. PMID- 2221840 TI - [Can CT scanner and MRI predict capsular invasion of local cancer of the prostate? A study of 20 radical prostatectomies]. AB - Spread beyond the capsule is a poor prognosis factor in clinically localized carcinomas of the prostate; preoperative diagnosis is difficult and clinical evaluation usually underestimates tumor spread. This prospective study was undertaken to confront results of the conventional workup (rectal examination, transrectal ultrasonography and PSA) and of CT scan and MRI findings with findings upon the pathologic study of operative specimens following radical prostatectomy. Results show that the conventional workup remains the diagnostic gold standard and that CT scan yields no additional information. Technically faultless MRI with sections in the three planes is a good means for analyzing the capsule of the prostate. PMID- 2221841 TI - Cholinergic deficiency and frontal dysfunction in Parkinson's disease. AB - To investigate the influence of central cholinergic deficit on cognitive function in Parkinson's disease (PD), we compared the neuropsychological performance of a group of 20 patients who were treated with anticholinergic drugs (mean daily dose, 10.2 mg) with that of a group of 20 patients who received no anticholinergics. The two groups were matched for all the variables of parkinsonism and levodopa therapy. At the dose used, there was no significant difference between the two groups of patients for intellectual, visuospatial, instrumental, and memory function. In contrast, in the group that received anticholinergics severe impairment was observed on tests believed to assess frontal lobe function. These results suggest that the lesion of the ascending cholinergic neurons, which has been demonstrated post mortem in PD, may play a role in the subcorticofrontal behavioral impairment of this disease. PMID- 2221842 TI - Posthypoxic glucose supplement reduces hypoxic-ischemic brain damage in the neonatal rat. AB - We evaluated the effect of posthypoxic glucose supplement in a neonatal hypoxic ischemic animal model. Seven-day-old rats underwent bilateral ligation of the carotid arteries, followed by exposure to an 8% oxygen atmosphere for 1 hour. The extent of hypoxic-ischemic brain damage was assessed histologically 72 hours later. Glucose load immediately after the end of the hypoxic exposure reduced the volume of neocortical infarction to 37% of the unsupplemented value, and attenuated ischemic damage in the striatum and the dentate gyrus. At the end of the hypoxic exposure, the brain level of glucose was 0.3 mmol/kg and the level of lactate 9 mmol/kg. Glucose supplement produced a rapid rise in brain glucose level to 3 to 5 mmol/kg over the next 2 hours. Lactate in both brain and plasma gradually fell toward the baseline level during the first hour of recovery. Posthypoxic glucose supplement slightly retarded lactate restitution. At any period of this neonatal model, brain lactate levels did not exceed the toxic level, which is postulated to be responsible for cerebral infarction in adult ischemic models. These results illustrate the important role of glucose in the development of neonatal hypoxic-ischemic encephalopathy and the fact that full cortical infarction can develop even if brain lactate levels are low. PMID- 2221844 TI - A computer simulation of conduction block: effects produced by actual block versus interphase cancellation. AB - A reduction in compound muscle action potential (CMAP) amplitude and area following proximal versus distal stimulation is the accepted clinical hallmark of conduction block; however, quantitative criteria for determining conduction block remain ambiguous. In this study, digitized records of individual motor unit action potentials (MUAPs) elicited by incremental stimulation in vivo were arithmetically combined in a computer simulation of CMAP generation. Through simulation of possible phase interaction patterns of individual MUAPs, we have shown that abnormal temporal dispersion alone can produce reductions in CMAP area of up to 50%, values that are commonly thought to represent conduction block. Furthermore, by simulating conduction block without excessive temporal dispersion in defined subpopulations of axons, we have demonstrated the importance of the fastest conducting (largest MUAP) axons in determining CMAP amplitude and area. In conclusion, measurements of CMAP amplitude and area in determining conduction block may be misleading if there is significant abnormal temporal dispersion, and quantitation of the degree of conduction block is difficult without knowledge of which subpopulations of axons are affected. PMID- 2221843 TI - Relation of hyperglycemia early in ischemic brain infarction to cerebral anatomy, metabolism, and clinical outcome. AB - We studied the relation of serum glucose level measured in the first 12 hours of symptoms to the clinical findings, results of computed tomography (CT), and patterns of cerebral metabolism in 39 patients who had acute ischemic cerebral infarction. Structural damage was assessed by CT. Metabolic disruption was assessed using 18F-fluorodeoxyglucose and positron emission tomography (PET). Median initial serum glucose concentration was 155 mg/dl (6.7 mM). Clinical recovery was significantly poorer in patients with initial serum glucose levels higher than the median (p less than 0.05, chi square). PET tended to show normal results or minor abnormalities in patients with initial glucose levels less than the median, as opposed to lobar or multilobe abnormalities in patients with levels that were higher than the median (p less than 0.05, Kendall's Tau b). The severity of hypometabolism in the ischemic region, expressed as the percent asymmetry of local cerebral glucose metabolism between homologous brain regions, was greater in patients with initial glycemia concentrations higher than the median (p less than 0.001, t test). Relationships of serum glucose level with metabolic derangement and structural damage, but not outcome, held true in patients without a history of diabetes mellitus. PMID- 2221845 TI - Soluble interleukin-2 receptors in cerebrospinal fluid from individuals with various neurological disorders. AB - Soluble interleukin-2 (IL-2R) levels in the cerebrospinal fluid (CSF) were studied in infectious, inflammatory, degenerative, and neoplastic disorders to evaluate their usefulness as a marker for the presence of activated T cells, thus indicating an inflammatory process. CSF from control subjects and patients with stationary, progressive, and treated multiple sclerosis (MS); aseptic meningitis; lymphoid and nonlymphoid central nervous system (CNS) tumors; Alzheimer's disease, as well as serum from MS patients and control subjects were studied for levels of soluble IL-2R. A significant increase in CSF IL-2R levels was observed in patients with MS, meningitis, and lymphoid CNS tumors; the MS group showed the highest values. CSF from individuals with Alzheimer's disease and from patients with nonlymphoid tumors did not show significantly elevated values. Serum IL-2R levels were significantly higher in MS patients than in control subjects, but there was no significant correlation between individual serum and CSF IL-2R levels. This study suggests the presence of activated T-lymphocytes in the CNS of patients with MS. PMID- 2221846 TI - Multiple sclerosis is prevalent in the Zoroastrians (Parsis) of India. AB - Using Schumacher's classification, we determined the prevalence rate of clinically definite multiple sclerosis (MS) in the distinct but tiny Zoroastrian (largely Parsi) community in the adjacent cities of Bombay (latitude, 18.55 degrees) and Poona (Pune). On prevalence day, 16 clinically definite cases of MS were counted, 14 in Bombay and 2 in Poona, from a total Zoroastrian population of 50,053 and 3,399, respectively. The crude prevalence ratio was 26 per 100,000 for Bombay and 58 per 100,000 for Poona. The age-adjusted prevalence ratio for Bombay was 24 per 100,000, with 95% confidence limits of 13.1 to 40.3. These are much higher than the low rates believed to be prevalent in India, and are comparable with those found in parts of Europe and the United States. PMID- 2221848 TI - Relapse of infant botulism. AB - We report on 3 infants who had relapse of infant botulism after apparent resolution of clinical symptoms. This group represented 5% of the infants with confirmed infant botulism who were treated at our institution since 1976. The exact cause for these relapses was unclear, but three potential mechanisms are examined. There were no historical, clinical, or electrophysiological predictors of relapse. Although at the time of writing recovery from relapse appeared complete, close follow-up of patients recovering from a bout of infant botulism is necessary. PMID- 2221847 TI - Middle cerebral artery strokes causing homonymous hemianopia: positron emission tomography. AB - Eight patients were evaluated with 18F-fluorodeoxyglucose positron emission tomography between 3 and 30 days after isolated stroke involving the middle cerebral artery territory that caused homonymous hemianopia. Diffuse hypometabolism was present throughout the damaged cerebral hemisphere, even in cortical areas not obviously ischemic by clinical examination or neuro-imaging. Glucose metabolism in primary and association visual cortex of the damaged hemisphere was decreased by more than 47% (p less than 0.01). Metabolism in the undamaged hemisphere was less profoundly affected, but significant decrements were found in calcarine (40%; p less than 0.01) and lateral occipital cortex (35%; p less than 0.05). PMID- 2221849 TI - HLA-DR antigens in Kleine-Levin syndrome. PMID- 2221850 TI - Nicotine and tobacco-induced nystagmus. PMID- 2221851 TI - Capsaicin for the treatment of pain in Guillain-Barre syndrome. PMID- 2221852 TI - 115th annual meeting of the American Neurological Association. October 14-17, 1990, Atlanta, GA. Abstracts. PMID- 2221853 TI - Newer uses of intravenous immunoglobulins as anti-infective agents. PMID- 2221854 TI - In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice. AB - The in vivo effects of antimicrobial agents against Toxoplasma gondii were evaluated in mice that were infected intraperitoneally with 10(4) tachyzoites of the RH strain by determination of survival rates and study of the kinetics of growth of T. gondii in infected mice. At various intervals after infection, subcultures of serial dilutions of blood, lung, and brain homogenates were performed in fibroblast tissue cultures for determination of parasitic loads. Pyrimethamine (18.5 mg/kg per day), sulfadiazine (375 mg/kg per day), and clindamycin (300 mg/kg per day) were administered for 10 days from day 1 or day 4 after infection. Untreated control mice died within 9 days and showed early and predominant lung involvement. All mice treated with sulfadiazine administered from day 1 survived and were apparently healthy; parasitic loads decreased early after treatment, but a relapse was observed 5 days after the cessation of therapy. When pyrimethamine was administered from day 1, 7 of 11 mice died within 25 days; by determination of parasitic loads, the effect of pyrimethamine was only demonstrable from day 6, and a relapse was constantly observed after the cessation of therapy. When pyrimethamine and sulfadiazine were administered in combination, 100% of mice survived; when therapy was started at day 1, parasites remained undetectable; in mice treated from day 4, parasites were eradicated by day 8 but infection relapsed 8 days after the cessation of therapy. All mice treated with clindamycin from day 1 or day 4 died within 10 days, but parasitemia was always undetectable. These results indicate that study of the kinetics of parasitic loads in blood and organs may provide additional information on the effect of antimicrobial agents against T. gondii in regard to the evolution of the infection and may represent a reliable basis for the determination of therapeutic regimens in humans. PMID- 2221855 TI - Problems with current recommendations for susceptibility testing of Haemophilus influenzae. AB - We compared results of MIC and disk susceptibility tests on Haemophilus test medium (HTM) and those on comparative media. Ampicillin MICs were determined with seven ampicillin-resistant, non-beta-lactamase-producing (AmprNBLP) isolates by using HTM and supplemented brain heart infusion (sBHI) agar. Ampicillin and amoxicillin-clavulanate disk tests with 16 AmprNBLP strains, 18 ampicillin susceptible (Amps) isolates, and 17 ampicillin-resistant, beta-lactamase producing (AmprBLP) strains were performed by using five media: laboratory prepared HTM (PHTM), commercial HTM (CHTM), sBHI, enriched chocolate agar, and Mueller-Hinton chocolate agar. We observed that five of seven and three of seven AmprNBLP strains were misclassified as susceptible with PHTM (MIC, less than 2 micrograms/ml) with inocula of 10(3) and 10(5) CFU, respectively, but were resistant with sBHI (MIC, greater than or equal to 2 micrograms/ml). Whereas Mueller-Hinton chocolate agar and enriched chocolate agar plates supported the growth of all 51 strains by the disk tests, 37% (19 of 51) and 8% (4 of 51) of strains did not grow on PHTM and CHTM, respectively. Lack of growth on PHTM was observed for all three phenotypes; 7 of 18 Amps, 4 of 17 AmprBLP, and 8 of 16 AmprNBLP strains did not grow. The four strains that did not grow on CHTM were all AmprNBLP isolates. Zone sizes were significantly larger on PHTM than on the other media. Of the strains that were evaluable by the new National Committee for Clinical Laboratory Standards guidelines with either PHTM or CHTM, all Amps strains were classified as susceptible. Among the AmprBLP strains, CHTM correctly identified all as resistant, whereas PHTM detected two isolates to be intermediate. Among the AmprNBLP strains, CHTM and PHTM misclassified four (33%) and five (62%) isolates, respectively, as susceptible; an additional isolate was identified as intermediate on both media. We conclude that there is strain dependent growth on HTM, that adoption of this medium for routine Haemophilus susceptibility testing is problematic due to this growth variability, and that detection of AmprNBLP isolates would be unreliable. PMID- 2221856 TI - Pharmacokinetics of enoxacin and its oxometabolite following intravenous administration to patients with different degrees of renal impairment. AB - Enoxacin is a fluorinated quinolone with potential clinical use in the treatment of serious infections. Twenty-three patients (age, 19 to 87 years) with different degrees of renal function, including a group undergoing chronic hemodialysis, received enoxacin (400 mg) by intravenous infusion (1 h). Blood samples were collected before infusion; at the end of infusion; and at 5, 10, 20, 30, 45, 60, 90, and 120 min and 3, 4, 6, 12, 18, 24, 48, and 72 h after infusion. Enoxacin and oxoenoxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters (mean +/- standard deviation) were calculated by using a noncompartmental PK model according to creatinine clearances (in milliliters per minute). Total clearance of enoxacin decreased from 4.95 +/- 1.16 ml/min per kg in the group with normal creatinine clearance to 0.76 +/- 0.21 ml/min per kg in the patients with severe renal failure (creatinine clearance, less than 15 ml/min), whereas the elimination half-life increased from 4.5 +/- 1.0 to 20 +/- 5 h, respectively. The elimination of oxoenoxacin (the main metabolite of enoxacin) in urine was markedly decreased when creatinine clearance was less than 15 ml/min. Hemodialysis removed an insignificant amount of enoxacin and oxoenoxacin. These data indicate that as creatinine clearance falls below 30 ml/min, the daily enoxacin dose should be reduced by half. During prolonged administration of enoxacin to patients with creatinine clearances of less than 30 ml/min, the accumulation of oxoenoxacin might lead to unexpected side effects. PMID- 2221857 TI - In vitro cultivation of Cryptosporidium parvum and screening for anticryptosporidial drugs. AB - Sporozoites of Cryptosporidium parvum which were excysted in vitro from oocysts isolated from calves or patients with acquired immune deficiency syndrome underwent development in monolayers of the mouse fibroblast cell line L929. Asexual multiplication occurred, with the maximum numbers of parasites usually being observed between 24 and 48 h after infection. Gametocytes were also found, but their numbers were relatively small compared with those of the asexual stages. A study was made of the effect on parasite development of 20 antimicrobial agents, most of which were anticoccidial or antimalarial agents. The majority of the drugs had a limited inhibitory effect on parasite development, but usually only at high concentrations. The two most active drugs were monensin and halofuginone, which reduced parasite multiplication by more than 90% at high concentrations. In the case of monensin, however, inhibition of parasite development at higher concentrations was due, at least in part, to a toxic effect of the drug on the host cells. PMID- 2221858 TI - Novel beta-lactamase from Capnocytophaga sp. AB - A novel beta-lactamase activity which confers resistance to expanded-spectrum cephalosporins and penicillins has been found in strain IC 5/21 of Capnocytophaga spp. Enzyme activity migrated at a molecular size of 38,000 daltons and at an isoelectric point of 3.6, with a minor band at 4.1. Kinetic studies suggested that it belonged to Richmond and Sykes beta-lactamase class 1c. Isoelectric focusing could be achieved only if a nonionic detergent was added to the gel, suggesting the presence of a hydrophobic enzyme akin to a membrane-bound beta lactamase of gram-positive bacteria. The location of the gene coding for this beta-lactamase is not yet known. PMID- 2221859 TI - Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells. AB - There is no consistently reliable treatment for endocarditis resulting from chronic Coxiella burnetii infection, the causative agent of Q fever. Although certain antibiotics are recommended on the basis of their in vitro bactericidal activities, results of therapy with these antibiotics are often disappointing. To evaluate whether the currently recommended antibiotic susceptibility tests for C. burnetii give misleading results because of continued division of uninfected cells, thereby resulting in the dilution of infected cells and, hence, a false picture of antibiotic efficacy, we blocked cell division during antibiotic susceptibility testing with cycloheximide. Using this new method, we found that the currently recommended antibiotics for the treatment of Q fever, doxycycline, pefloxacin, and rifampin, did not reduce the ratio of infected to noninfected cells (either L929 or P388D1) by 9 days postinfection. To test the hypothesis that this lack of antibacterial activity is due to antibiotic inactivation by the low pH of the phagolysosomes in which C. burnetii is found, we used alkalinizing lysosomotropic agents (chloroquine or amantadine) concurrently with doxycycline. This resulted in the sterilization of C. burnetii infection in P388D1 cells. This finding seems to confirm our suspicion that the acidic conditions of the phagolysosomes in which C. burnetii is located inhibit antibiotic activity. This inhibition can be reversed in vitro when lysosomotropic alkalinizing agents are used. PMID- 2221860 TI - Meropenem pharmacokinetics and penetration into an inflammatory exudate. AB - The pharmacokinetics and penetration into a cantharidine-induced inflammatory exudate of meropenem was studied in six volunteers following a single 1-g intravenous dose. Concentrations in plasma, urine, and the inflammatory exudate were determined by a microbiological assay. The mean elimination half-life of meropenem in plasma was 1.1 h, with the concentration in plasma declining from a mean of 23.6 micrograms/ml at 1 h to 0.7 micrograms/ml at 6 h. The inflammatory fluid penetration was rapid (time to maximum concentration of drug in serum, 0.75 h), and the penetration was 111%. The recovery of meropenem in urine at 24 h was 65.4% of the administered dose. PMID- 2221861 TI - Mode of action of tubulozoles against Plasmodium falciparum in vitro. AB - The mode of action of the tubulozole isomers, recently recognized as a new class of potential antimalarial agents, was investigated. Whereas neither glycolysis, protease activity, or nucleic acid biosynthesis was primarily affected, protein biosynthesis decreased soon after addition of the drug. Inhibitors of protein biosynthesis, however, did not show synergistic activity with tubulozole. Colcemid, on the other hand, had an effect on protein synthesis similar to that seen with the tubulozoles. Furthermore, combinations of the tubulozole isomers with compounds known to interact with tubulin inhibited malaria in a synergistic or antagonistic fashion. Therefore, the inhibition might be elicited by interaction with tubulin or some other component of the microtubules. This is remarkable insofar as only one of the tubulozole isomers affects mammalian cells by binding to tubulin. PMID- 2221862 TI - Branched-chain fatty acids produced by mutants of Streptomyces fradiae, putative precursors of the lactone ring of tylosin. AB - Three branched-chain fatty acids (7-hydroxy-4,6-dimethylnona-2,4-dienoic acid [compound 1], its 7-epimer [compound 2], and 7-keto-4,6-dimethylnona-2,4-dienoic acid [compound 3]) and a ketone (9-hydroxy-6,8-dimethylundeca-4,6-dien-3-one [compound 4]) were isolated from the culture broth of mutants of Streptomyces fradiae which were blocked in the biosynthesis of the macrolide antibiotic tylosin. Two phenotypic classes of mutants of this organism which were blocked in the addition of mycaminose to tylactone (compound 6) accumulated these compounds. These compounds were not produced by mutants which were blocked in lactone synthesis, in steps beyond mycaminose addition, or by the wild-type strain. Synthesis of these compounds, like synthesis of tylosin, was inhibited by the addition of cerulenin. Compounds 1, 2, and 3 were partially interconvertible by these mutants; but they were not produced from the degradation of tylactone and they were not directly incorporated into tylosin by intact cells. The structures of compounds 1 and 2 were equivalent to that of a predicted intermediate (S. Yue, J. S. Duncan, Y. Yamamoto, and C. R. Hutchinson, J. Am. Chem. Soc. 109:1253-1255, 1987) in the biosynthesis of tylactone. The ketone (compound 4) reported previously (N. D. Jones, M. O. Chaney, H. A. Kirst, G. M. Wild, R. H. Baltz, R. L. Hamill, and J. W. Paschal, J. Antibiot. 35:420-425, 1982) appears to be the decarboxylation product of the intermediate following that represented by compound 1. This represents the first report of the isolation of putative precursors of tylactone from tylosin-producing organisms. PMID- 2221863 TI - Effects of incubation temperature, inoculum size, and medium on agreement of macro- and microdilution broth susceptibility test results for yeasts. AB - We examined the effects of temperature and inoculum on the agreement of macro- and microdilution broth MICs of five antifungal agents against six isolates of Candida species or Torulopsis glabrata. Incubation temperature affected results with amphotericin B, flucytosine, fluconazole, and SCH 39304, producing better agreement at 35 degrees C than at 37 degrees C. Agreement between methods was better with an inoculum size of 10(2) than with one of 10(4) yeast cells per ml in testing fluconazole or SCH 39304, and the discrepancies seen with a higher incubation temperature and a larger inoculum appeared to be additive. However, inoculum size did not seem to affect agreement between methods in testing amphotericin B, flucytosine, or ketoconazole. Regardless of test conditions, macrodilution broth MICs of amphotericin B for different isolates were strikingly higher than microdilution test MICs, with mean differences being greater than ninefold under some test conditions. We conclude that for most currently available antifungal agents, an incubation temperature of 35 degrees C and a starting yeast inoculum of less than 10(4) cells per ml improve the agreement between macro- and microdilution broth tests. PMID- 2221864 TI - Beta-lactamase production and susceptibilities to amoxicillin, amoxicillin clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole of 320 non-Bacteroides fragilis Bacteroides isolates and 129 fusobacteria from 28 U.S. centers. AB - beta-Lactamase production (nitrocefin disk method) and agar dilution susceptibility of amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin clavulanate, cefoxitin, imipenem, and metronidazole were determined for 320 Bacteroides species (not Bacteroides fragilis group) and 129 fusobacteria from 28 U.S. centers. Overall, 64.7% of Bacteroides species and 41.1% of fusobacteria were beta-lactamase positive. Among the Bacteroides species, positivity rates were highest for B. bivius (85.0%), followed by B. splanchnicus (83.3%), B. eggerthii (77.8%), and B. oralis (77.1%); 54.5% of black-pigmented Bacteroides species were beta-lactamase positive. Among the fusobacteria, Fusobacterium mortiferum showed the highest rate of beta-lactamase positivity (76.9%). MICs of amoxicillin (128 micrograms/ml) and ticarcillin (64 micrograms/ml) for 90% of all beta-lactamase-positive strains were reduced to 4 and 2 micrograms/ml, respectively, with the addition of clavulanate. MICs of amoxicillin and ticarcillin for 90% of all beta-lactamase-negative strains were 1 and 4 micrograms/ml, respectively, and greater than or equal to 98.4% of the strains were susceptible to the beta-lactams tested. Of the beta-lactamase-producing strains, 45.9% were susceptible to amoxicillin at less than or equal to 4 micrograms/ml and 93.4% were susceptible to ticarcillin at less than or equal to 64 micrograms/ml; the addition of clavulanate raised the rates to 90.4 and 100%, respectively. All strains were susceptible to cefoxitin, imipenem, and metronidazole. The activity of amoxicillin against 29 beta-lactamase-producing strains (10 Bacteroides species and 19 fusobacteria) was not enhanced by the addition of clavulanate; however, 82.7% of these strains were susceptible to amoxicillin, and all were susceptible to ticarcillin. Although beta-lactamase positivity is on the increase in non-B. fragilis group Bacteroides species and fusobacteria, amoxicillin-clavulanate, ticarcillin, cefoxitin, imipenem, and metronidazole should be suitable for the treatment of infections with these strains. The addition of clavulanate does not appreciably improve the efficacy of ticarcillin against these organisms. PMID- 2221865 TI - Effects of timing of food and fluid volume on cefetamet pivoxil absorption in healthy normal volunteers. AB - Cefetamet pivoxil (1,000 mg orally) absorption was evaluated in 16 male subjects (age, 23.4 +/- 1.7 years; weight, 73.9 +/- 7.0 kg) 1 h before (BE), with (WI), and 1 h after (AF) a standard breakfast. The time to peak concentration of cefetamet in plasma (Tmax) was increased from 3.25 +/- 1.44 h in the BE group to 4.31 +/- 1.54 and 4.13 +/- 1.54 h in the WI and AF groups, respectively (P less than 0.05). The maximum cefetamet concentration in plasma (Cmax) and the area under the plasma cefetamet concentration-time profiles (AUC) in the BE, WI, and AF groups were 5.50 +/- 1.06, 5.47 +/- 1.4, and 6.57 +/- 0.93 micrograms/ml and 38.2 +/- 10.1, 35.7 +/- 11.9, and 42.8 +/- 6.8 micrograms.h/ml, respectively. The Cmax and AUC values were not different between the BE and WI groups (P greater than 0.05). However, differences in these values were found between the WI and AF groups (P less than 0.05). The effect of fluid volume intake on cefetamet pivoxil (1,000 mg orally) absorption was evaluated in 12 male subjects (age, 23.8 +/- 2.3 years; weight, 74.9 +/- 9.0 kg) under fasted and WI conditions. Increasing fluid volume intake from 250 to 450 ml under the fasted condition had no effect on the absorption of the prodrug (Tmax, 2.50 +/- 0.52 versus 2.83 +/- 0.94 h; Cmax, 4.89 +/- 1.04 versus 4.84 +/- 0.89 micrograms/ml; AUC, 29.6 +/- 5.1 versus 30.7 +/- 7.1 micrograms.h/ml; P greater than 0.05. Thus, independent of fluid volume intake, cefetamet pivoxil absorption is enhanced when it is given within 1 h of a meal, and it is recommended that the prodrug should be taken during this period of increased bioavailability. PMID- 2221866 TI - SCH-39304 in prevention and treatment of disseminated candidiasis in persistently granulocytopenic rabbits. AB - To investigate the potential use of SCH-39304 for the prevention and treatment of disseminated candidiasis in granulocytopenic patients, we studied its in vivo antifungal activity as preventive, early, and late treatments in three models (acute, subacute, and chronic) of disseminated candidiasis in persistently granulocytopenic rabbits. SCH-39304 was an effective as amphotericin B alone and fluconazole alone for the prevention of disseminated candidiasis. SCH-39304 alone and fluconazole alone were as effective as amphotericin B plus flucytosine for early treatment of subacute disseminated candidiasis. When treatment was delayed for 5 days to establish chronic disseminated candidiasis, SCH-39304 was less effective than amphotericin B plus flucytosine. In comparison with different treatment regimens, SCH-39304 was more effective in early and preventive treatment. Thus, SCH-39304 was comparable to treatment control regimens in prevention and early treatment of subacute disseminated candidiasis. SCH-39304 also was most effective in granulocytopenic rabbits with disseminated candidiasis when used for prevention or early treatment. PMID- 2221867 TI - Cloning of SHV-2, OHIO-1, and OXA-6 beta-lactamases and cloning and sequencing of SHV-1 beta-lactamase. AB - Molecular cloning of DNA fragments permitted the isolation of structural genes coding for SHV-1, SHV-2, OHIO-1, and OXA-6 beta-lactamases. DNA probes were constructed for SHV-1, and under conditions of high stringency, hybridization was observed only between SHV-1 and SHV-2. Oligonucleotide typing with a 15-mer SHV-1 probe was capable of discriminating between SHV-1 and SHV-2 but not OHIO-1. The nucleotide sequence of the SHV-1 beta-lactamase gene from plasmid R974 has been determined. The structural gene encodes a polypeptide product which differs by 9 residues from the p453 (SHV-1) PIT-2 enzyme determined by peptide sequencing. The significance of each mutation was assessed by alignment of amino acid sequences and comparisons with the Staphylococcus aureus PC1 penicillinase crystal structure. Structural similarities between SHV-1 and class A beta-lactamases are extensive, with amino acid identities of 88.9% between SHV-1 and LEN-1, 91.8% between SHV-1 and OHIO-1, and 63.7% between SHV-1 and TEM-1. PMID- 2221868 TI - Enhanced action of amphotericin B on Leishmania mexicana resulting from heat transformation. AB - A comparative study of the effect of the polyene antibiotic amphotericin B (AmB) on the viability of Leishmania mexicana promastigotes before and after their transformation by heat into amastigotelike forms was carried out. The kinetics of cell death were followed by spectrofluorometry with the nucleic acid-binding compound ethidium bromide. It was found that the rapid killing effect that is exerted by AmB on Leishmania promastigotes was even faster after their transformation into amastigotelike forms. Binding studies of AmB to Leishmania membranes by circular dichroism indicated that heat transformation modified it from noncooperative to cooperative binding, decreasing the amount of antibiotic that bound to the membranes. Thus, the increased rate of ethidium bromide incorporation into transformed cells was not related either to the amount of AmB bound or to an increased amount of ergosterol in the membrane (the ergosterol/phospholipid ratio was four times smaller after heat shock). An increase in the Mg2+ content of the external aqueous solution was able to prevent the AmB-induced incorporation of ethidium bromide into Leishmania promastigotes to a greater extent (Ki = 13.8 mM) than it was into heat-transformed cells (Ki = 64 mM), suggesting that there were significant changes at the Leishmania cell surface on heat transformation. The significance of these results for understanding the mechanism of action of AmB on sensitive organisms is discussed. PMID- 2221869 TI - In vitro susceptibility of Ehrlichia sennetsu to antibiotics. AB - Antibiotic efficacies were evaluated by Diff-Quik (Dade, Dudingen, Federal Republic of Germany) staining of Ehrlichia sennetsu in P388D1 murine macrophages grown in 96-well microtiter plates. Sennetsu disease is generally cured with tetracyclines. In vivo, E. sennetsu is susceptible to doxycycline and is resistant to erythromycin, penicillin, and chloramphenicol. Our study confirmed, in vitro, the efficacy of doxycycline, which had an MIC of 0.125 micrograms/ml. E. sennetsu was found to be resistant to erythromycin, chloramphenicol, penicillin, gentamicin, and co-trimoxazole, while it was very susceptible to ciprofloxacin (MIC, 0.125 micrograms/ml) and rifampin (MIC, 0.5 micrograms/ml). PMID- 2221870 TI - Activity of compound G2 isolated from alfalfa roots in experimental dermatophyte infection. AB - Compound G2 isolated from alfalfa roots was applied topically to skin lesions of guinea pigs experimentally infected with the dermatophyte Trichophyton mentagrophytes var. granulare. After 12 to 15 applications, 80% of the infected lesions were cured, as judged by clinical and microbial criteria, compared with 20% of the untreated lesions which healed spontaneously (P less than 0.01). PMID- 2221871 TI - Comparison of ofloxacin, gentamicin, and tobramycin concentrations in tears and in vitro MICs for 90% of test organisms. AB - Concentrations of three anti-infective agents in tear film were monitored after one topical application in rabbits. Ofloxacin concentrations exceeded the MIC for 90% of the organisms tested (MIC90) (gram-negative and gram-positive organisms) for 240 min. Tobramycin concentrations exceeded the MIC90 for 10 min. Gentamicin concentrations exceeded the MIC90 for 20 min for gram-positive organisms and 120 min for gram-negative organisms. PMID- 2221872 TI - In vitro susceptibility of Xanthomonas (Pseudomonas) maltophilia to newer antimicrobial agents. AB - The susceptibilities of 45 clinical and 3 environmental isolates of Xanthomonas maltophilia to 14 antimicrobial agents was determined by broth microdilution. The newer quinolones PD117596, PD117558, PD127391, A-56620, amifloxacin, and fleroxacin were the most active agents tested, with 70 to 99% of isolates being susceptible to these agents. All isolates were resistant to trospectomycin. The new aminoglycosides SCH24120 and SCH22591 were active against 12 and 1% of isolates, respectively. PMID- 2221873 TI - Gene heterogeneity for tetracycline resistance in Staphylococcus spp. AB - Nucleotide sequences related to four tet genes were studied by hybridization in 183 clinical Staphylococcus isolates. tet(K) predominated in strains resistant only to tetracycline, while tet(M) was responsible for combined tetracycline and minocycline resistance. In strains harboring both genes, they contributed additively. tet(L) was detected in only five strains, and no hybridization was observed with tet(O). PMID- 2221874 TI - Blockage of cell wall receptors for yeast killer toxin KT28 with antimannoprotein antibodies. AB - Binding of yeast killer toxin KT28 to its primary cell wall receptor was specifically blocked with polyclonal antimannoprotein antibodies which masked all toxin-binding sites on the surface of sensitive yeast cells. By indirect immunofluorescence, it was shown that KT28 binds to the cell wall mannoprotein and that the toxin resistance of mannoprotein mutants (mnn) of Saccharomyces cerevisiae was due to a lack of killer toxin-binding sites within the yeast cell wall. Structural analysis of acetylated mannoprotein from KT28-resistant mutant strains identified the outer mannotriose side chains as the actual killer toxin binding domains. PMID- 2221877 TI - Assessing ECG rhythms is part of perioperative nursing. PMID- 2221876 TI - The search for common standards and guidelines is a collaborative effort. PMID- 2221875 TI - Comparison of cilofungin and amphotericin B for therapy of murine candidiasis. AB - We compared the efficacies of cilofungin and amphotericin B treatment in a murine model of disseminated candidiasis. Three different dosages of each drug plus controls were evaluated. Statistically improved survival was noted only among mice treated with 1 mg of amphotericin B per kg of body weight (P less than 0.05). While all amphotericin B regimens and the two lower-dosage cilofungin regimens significantly reduced yeast cell counts in kidneys compared with the controls, the amphotericin B-treated mice had a significantly higher percentage of sterile kidneys following therapy compared with those treated with cilofungin (P = 0.0001). PMID- 2221878 TI - Many hospitals ignore AIDS testing guidelines. PMID- 2221879 TI - Hepatic resection. Indications, procedures, patient care. PMID- 2221880 TI - Reduced-size liver transplantation. Hope for pediatric patient with end-stage liver disease. PMID- 2221881 TI - Electrocardiogram monitoring. Interpreting normal cardiac rhythms. PMID- 2221882 TI - Electrocardiogram monitoring. Interpreting abnormal cardiac rhythms. PMID- 2221883 TI - Inguinal hernia repairs. Types, patient care. PMID- 2221884 TI - Thyroid storm. Potential perioperative crisis. PMID- 2221885 TI - OR nurse turnover. Collecting pertinent data to analyze the problem. PMID- 2221886 TI - BSNs for RNs. An off-campus program may be the answer. PMID- 2221887 TI - Preparing for the CNOR exam. An independent study plan that worked. PMID- 2221888 TI - Surgical positions. Their effects on cardiovascular, respiratory systems. PMID- 2221889 TI - AORN recommended practices. A valuable resource, not policy. PMID- 2221890 TI - Proposed recommended practices: electrosurgery. Association of Operating Room Nurses. PMID- 2221891 TI - Agency for the blind receives grant for AIDS project. PMID- 2221892 TI - Proposed recommended practices: surgical tissue banking. Association of Operating Room Nurses. AORN Recommended Practices Coordinating Committee. PMID- 2221893 TI - Issues involving stockless inventory systems. PMID- 2221894 TI - The risk of carpal tunnel syndrome with computer use. PMID- 2221895 TI - Projecting a positive image is important when dealing with patients and other health care professionals. PMID- 2221896 TI - Making choices: the crux of ethical problems in nursing. PMID- 2221897 TI - Beating the heat during pediatric surgery. PMID- 2221898 TI - The challenges of conducting clinical nursing research with elderly populations. PMID- 2221899 TI - Using wall suction for evacuating laser plumes. PMID- 2221900 TI - Signing operative permits in the holding room. PMID- 2221901 TI - An obituary for the nursing care plan. PMID- 2221902 TI - Computerized preference lists. Using computers to integrate and improve patient care. PMID- 2221903 TI - Chemical dependency in nursing. Identifying and helping the troubled nurse. PMID- 2221904 TI - Peripheral vascular angioscopy. Performance, equipment, technique. PMID- 2221905 TI - Patient assessment. Conducting an effective interview. AB - The patient interview is a complex process that requires the interviewer to have a high degree of skill. By improving interviewing skills, nurses can become more adept at obtaining valid information from patients. With the knowledge they obtain from successful interviews, nurses can continue to plan and implement the care each patient requires. PMID- 2221906 TI - Hernia repair with polypropylene mesh. An improved method. PMID- 2221907 TI - Preoperative teaching videotape. The effect on children's behavior. PMID- 2221908 TI - Malignant hyperthermia crisis. Planning a mock demonstration. PMID- 2221909 TI - Pharmacologic actions of commonly used preoperative medications. PMID- 2221910 TI - Ethical issues involved with in vitro fertilization. AB - There are three elements to consider with in vitro fertilization. First, the paramount concern needs to be the well-being and best interests of the child, even though he or she may be an embryo at the time. Second, some people think a child will solve their marital problems. Although couples seeking in vitro fertilization should not be subjected to more scrutiny than couples conceiving in the traditional way, the stresses and uncertainties of in vitro fertilization can further strain a marriage. Clinic staff members should be sensitive to this issue as a way of helping to avoid complications later. Third, how we resolve the status and fate of the frozen embryo and who has disposition over it surely will reflect how we consider abortion rights. For example, if the standards of Roe vs Wade were applied, one could argue that the woman should have total disposition over the frozen embryo. On the other hand, if the father receives a say in the matter, what impact would this have? Given the nature of our society and the tenuous state of marriage, the problem of disposing frozen embryos is a critical one that has no satisfactory solution. Finally, there is the stress factor. Although this is not an issue of direct ethical concern, it is related to the necessity of the couple receiving accurate information. If the couple receives an incorrect impression of a clinic's success rates, they may be exposed unnecessarily to further stress and frustration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221911 TI - Rat renal proximal tubular gluconeogenesis: possible involvement of nonmitochondrial carbonic anhydrase isozymes. AB - The carbonic anhydrase (CA) inhibitor ethoxzolamide decreases the rate of glucose synthesis from 10 mM pyruvate by tubules incubating in 25 mM HCO3- but not in 50 mM HCO3-: this is evidence that rat renal cortical mitochondrial CA (CA V) provides HCO3- for pyruvate carboxylation in renal tubular gluconeogenesis at physiological total CO2 (CO2 + HCO3-). In renal proximal tubules prepared from 48 h-starved rats and incubating in 10 mM pyruvate in 25 mM HCO3- buffered saline (Krebs-Henseleit buffer) the CA inhibitors acetazolamide (AZ) and benzolamide (BZ) decreased the rate of glucose synthesis. Maximal inhibition was reached with 125 microM AZ or with 450 microM BZ. The rate of glucose synthesis increased with increasing pyruvate concentration from 3.33 to 20 mM; including 600 microM BZ or 188 microM AZ results in glucose synthesis becoming independent of increasing pyruvate concentration. Doubling the physiological concentration of bicarbonate restored the dependence of glucose synthesis on pyruvate concentration and partly, but not completely, alleviated the inhibitory effect of AZ and BZ, leading to the conclusion that AZ and BZ influence gluconeogenesis by affecting enzymes in addition to CA V. Tubules were incubated with substrates which do not require pyruvate carboxylation for synthesis of oxaloacetate. When tubules were incubated in 10 mM malate the rate of glucose synthesis was unaffected by less than 100 microM AZ or 400 microM BZ and was decreased maximally by 40 and 20%, respectively, by 125 microM AZ, 450 microM BZ, and higher concentrations of these drugs. Increasing the malate concentration from 3.33 to 20 mM increased the rate of glucose synthesis; 600 microM BZ inhibited the rate of glucose synthesis only when the malate concentration was greater than 10 mM but 188 microM AZ decreased the rate of glucose synthesis at each concentration of malate. Results were similar when tubules were incubated in glutamine with CA inhibitors. The rate of glucose synthesis differed with the substrate metabolized and the substrate concentration except when 600 microM BZ was included.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2221913 TI - Yeast thioltransferase--the active site cysteines display differential reactivity. AB - Thioltransferase, catalyzing thiol-disulfide interchange between reduced glutathione and disulfides, was purified to homogeneity from Saccharomyces cerevisiae. The purification procedure included ammonium sulfate precipitation, Sephadex G-50 gel filtration, CM-Sepharose ion exchange chromatography, and C18 reverse phase high pressure liquid chromatography. Two thioltransferase activity peaks were resolved by CM-Sepharose chromatography. The protein from the major peak had a molecular weight of 12 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis while the minor peak protein migrated slightly faster in this gel system. Both proteins showed similar amino acid compositions and identical N termini. The major peak of thioltransferase was extensively characterized. Plots of thioltransferase activity as a function of S-sulfocysteine or hydroxyethyl disulfide concentration did not show normal Michaelis-Menten kinetics. The enzyme activity had a pH optimum of 9.1. The protein has 106 amino acid residues with two cysteines and no arginine. The active site amino acid sequence of the enzyme was identified as Cys26-Pro-Tyr-Cys29, which is similar to that of mammalian thioltransferase and Escherichia coli glutaredoxin. The two cysteines at the active site displayed different reactivities to iodoacetamide. Cys26 was alkylated by iodoacetamide at pH 3.5 while Cys29 was alkylated at pH 8.0. The enzyme was completely inactivated when the Cys26 was carboxymethylated. A plot of incorporation of iodoacetamide into Cys29 at different pHs was similar to the pH dependence of the enzyme activity. The result suggested that Cys26 could readily initiate nucleophilic attack on disulfide substrates at physiological pH. PMID- 2221912 TI - beta-Glucuronidase is transported slowly to lysosomes in BW5147 mouse lymphoma cells: evidence that the prelysosomal enzyme is not restricted to the endoplasmic reticulum. AB - The post-translational processing of beta-glucuronidase in BW5147 mouse lymphoma cells is slow relative to other newly synthesized lysosomal enzymes. To characterize this slow maturation the acid hydrolase was immunoprecipitated from cells pulse-labeled with [2-3H]mannose. Radiolabeled beta-glucuronidase migrated as the precursor form of the enzyme for up to 4 h of chase, whereas another acid hydrolase, beta-galactosidase, was processed completely to its mature form within this same time period. Both beta-glucuronidase and beta-galactosidase obtained high levels of mannose 6-phosphate (Man 6-P) within 60 min of their biosynthesis. The Man 6-P content of beta-galactosidase declined rapidly during a subsequent chase while that of beta-glucuronidase remained high during the first 4 h of chase and then slowly declined. 3H-Labeled phosphorylated high mannose-type oligosaccharides isolated from beta-glucuronidase after 1 h of chase were composed primarily of species with one or two phosphodiester groups, but oligosaccharides with one and two phosphomonoesters became the predominant phosphorylated species with longer chase times. The phosphorylated oligosaccharides attached to other newly synthesized acid hydrolases, on the other hand, contained primarily phosphodiester species at all chase times. When BW5147 cells were pulsed with [3H]mannose and chased in the presence of monensin to disrupt transport, the number of phosphorylated oligosaccharides recovered from beta-glucuronidase was comparable to the quantity recovered from the enzyme produced by non-drug-treated cells. The number of phosphorylated units recovered from all other newly synthesized acid hydrolases, however, was greater in the presence of the ionophore than in its absence. Nondenaturing gel electrophoresis studies indicated that beta-glucuronidase existed in two forms at steady state within BW5147 cells and, as such, was similar to liver beta-glucuronidase in which a large percentage of the enzyme was present as a complex bound to egasyn. These data suggest that newly synthesized beta-glucuronidase produced by BW5147 cells complexes with an egasyn-like protein within the endoplasmic reticulum. This interaction retards the enzyme's migration through the secretory apparatus but does not prevent its access to Golgi-associated processing enzymes. PMID- 2221914 TI - Structural and functional studies of the rat mitochondrial single strand DNA binding protein P16. AB - The rat mitochondrial single strand DNA binding protein (SSB) P16 was purified to apparent homogeneity by elution from single strand DNA agarose with ethidium bromide. Each monomer of P16 contains two tryptophan residues, and the intrinsic fluorescence from these residues is quenched upon binding to single strand polynucleotides. From fluorescence quench titrations of ligand to fixed amounts of DNA lattice, a binding site size of 8 or 9 nucleotides per P16 monomer was found. Measurement of the affinity of P16 for isolated sites by titration with either oligo(dT)8 or 5'-dephosphorylated oligo(dT)8 indicated values on the order of 10(7) M-1. P16 exhibited a binding preference for single strand DNA, poly(dT), and poly(dC) in comparison to double strand DNA, poly(U), or poly[d(A-T)]. Although it was not possible to show that P16 destabilizes double helical DNA or even poly[d(A-T)], binding of P16 does inhibit the process of renaturation as shown by inhibition of duplex formation between poly(dA) and poly(dT). The binding of saturating amounts of P16 to single strand poly(dT).oligo(dA)50 template-primers enhanced approximately 10-fold the activity of both the homologous mitochondrial DNA polymerase and the Escherichia coli DNA polymerase I Klenow fragment. However, the mitochondrial DNA primase was nearly completely inhibited by the saturation of the poly(dT) template with P16. Amino-terminal sequence analysis of P16 and a protease-insensitive, DNA binding domain (Mr approximately 6000) revealed that the DNA binding domain residues, at least in part, in the amino-terminal third of the P16 molecule. Furthermore, the amino terminal sequence was found to be strikingly similar to that of the Xenopus laevis mtSSB-1 and to a lesser extent similar to E. coli SSB and E. coli F sex factor SSB. PMID- 2221915 TI - Transient expression of type 2 chain in A-active hexaglycosylceramide of rat small intestine at weaning time. Demonstration by affinity chromatography and ceramide glycanase hydrolysis of A-active glycosphingolipids followed by gas chromatography and mass spectrometry of permethylated hexasaccharides. AB - The small intestine of 15- to 23-day-old rats was cut into four segments from the duodenum to the ileum. Neutral glycosphingolipids were purified from each segment and submitted to thin-layer chromatography and immunostaining with the A005 monoclonal anti-A antibody. This antibody detected an hexaglycosylceramide located mainly in the duodenum during the postnatal development. In order to characterize hexaglycosylceramides, blood group A-active glycolipids were purified by affinity chromatography on immobilized Helix pomatia lectin in organic solvent. Hexaglycosylceramides (A-6) were subsequently isolated by preparative thin-layer chromatography and hydrolyzed with ceramide glycanase. The free hexasaccharides were permethylated and analyzed by gas chromatography. Two peaks were detected in varying ratios during development, corresponding to type 1 and type 2 chain A hexasaccharides. Gas chromatography clearly demonstrated that type 2 A-6 occurred in the duodenum of developing rats, and that a shift from type 2 to type 1 A-6 occurred with growing age. The change from type 2 to type 1 chain was also assessed by methylation analysis, and by the variation of the characteristic fragmentations of type 1 and type 2 chain hexasaccharides upon mass spectometry of the permethylated A-6 oligosaccharides from the duodenum of 19-day-old and adult rats. PMID- 2221916 TI - Regional differences in the appearance of adult-type glycosphingolipids in the small intestine of inbred rats at weaning time. AB - The small intestine of 15- to 33-day-old rats was cut into four segments: duodenum, proximal jejunum, distal jejunum, and ileum. Neutral glycosphingolipids and gangliosides were purified from each segment and analyzed by thin-layer chromatography in order to study the developmental appearance of adult-type glycolipids at each level of the small intestine. Type 1 A-6 glycolipid was first detected in the ileum at 15 days and subsequently in the jejunum and duodenum at 19 days of age. N-Glycolylneuraminic acid was expressed first in the ileum at 17 days, then in the proximal jejunum at 21 days, but only after 29 days in the duodenum. In each region, 6-8 days were required between first detection and full expression of N-glycolylneuraminic acid. The presence of 2-hydroxylated fatty acids in glucosylceramide was found first in the ileum at 19 days, 2-3 days before appearing in the duodenum and proximal jejunum. A period of 2-3 days was necessary to reach full adult-type level of 2-hydroxylated fatty acids in glucosylceramide. These results show that adult-type glycolipids appear earlier in the distal than in the proximal region of the rat small intestine, and that different glycolipids appear at different times and at different rates. The finding that the biochemical differentiation of the whole small intestine expands over a period of 3 days to 2 weeks, depending on the region and the glycolipid, before being fully completed indicates that, in addition to the time lag observed between the distal and the proximal region, the new cells arising from the crypt of Lieberkhun after 15 days of age are not at once fully differentiated. PMID- 2221917 TI - Purification and characterization of flavone synthase I, a 2-oxoglutarate dependent desaturase. AB - Soluble flavone synthase I from illuminated parsley cells was purified to near homogeneity by a six-step procedure. A molecular mass of 48 +/- 2 kDa was determined by gel permeation chromatography and denaturing polyacrylamide gel electrophoresis. A single protein with an isoelectric point at pH 4.8 +/- 0.1 was detected on isoelectric focusing gels, which catalyzed the overall conversion of 2S-flavanones into the corresponding flavones in the presence of molecular oxygen, 2-oxoglutarate, ferrous ion, and ascorbate. Apparent Michaelis constants for 2S-naringenin, 2S-eriodictyol, and 2-oxoglutarate were determined as 5, 8, and 16 microM, respectively. (+)-Dihydrokaempferol and 2R-naringenin were not accepted as substrates. The enzyme was strongly inhibited by Cu2+ and Zn2+. Potent competitive inhibition with respect to 2-oxoglutarate was observed with 2,4-pyridinedicarboxylate (Ki = 1.8 microM). With crude extracts as well as with the purified enzyme neither the hypothetical intermediate 2-hydroxyflavanone nor a dehydratase activity capable of converting the chemically synthesized compound to flavone could be observed. Moreover, the introduction of the double bond into the substrate naringenin was not altered by addition of chemically synthesized 2 hydroxynaringenin into the reaction mixture. Therefore, 2-hydroxyflavanones are apparently not freely dissociable intermediates in the biosynthesis of flavones in parsley and are not capable of entering the active site of the enzyme to compete with the flavanone. It is postulated that flavone synthase I catalyzes double-bond formation by direct abstraction of vicinal hydrogen atoms at C-2 and C-3 of the substrate. Thus, flavone synthase I is a member of a novel subgroup within the 2-oxoglutarate-dependent dioxygenases that can be referred to as 2 oxoglutarate-dependent desaturases. PMID- 2221918 TI - Reactivity of ebselen and related selenoorganic compounds with 1,2-dichloroethane radical cations and halogenated peroxyl radicals. AB - The reactivity of ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)one, and structurally related analogues was studied by pulse radiolysis. The rate constant for the reaction of ebselen with trichloromethylperoxyl radicals was determined to be 2.9 X 10(8) M-1 s-1, while its sulfur analogue, 2-phenyl-1,2-benzisothiazol 3(2H)one, was oxidized at much lower rates, k less than or equal to 10(7) M-1 s 1. Among several derivatives studied, the only other compound that exhibited a high rate constant was 2-(methylseleno)-benzoic acid-N-phenylamide. Oxidation of ebselen by other halogenated peroxyl radicals was also carried out and revealed a direct relationship between rate constant and the degree of halogenation of the oxidant. The transient radicals generated during oxidation of ebselen and the analogues were characterized by optical absorption and conductivity measurements and were attributed to one-electron-oxidized radical cations. The oxidation potentials were determined by cyclic voltammetry. Comparative evaluation of the in vitro behavior during microsomal lipid peroxidation revealed ebselen to be the most potent antioxidant of the compounds investigated, 2-(Methylseleno)-benzoic acid-N-phenylamide, despite its high rate constant for oxidation by halogenated peroxyl radicals, was found to be a poor antioxidant. The rate constant of oxidation of ebselen by trichloromethylperoxyl radicals is comparable to that of alpha-tocopherol under similar conditions, underscoring the potential pharmacological interest of ebselen as an antioxidant. PMID- 2221919 TI - Base modifications in plasmid DNA caused by potassium permanganate. AB - KMnO4 is a powerful oxidizing agent which has been used to modify DNA bases. In previous studies, mild KMnO4 treatment has been shown to preferentially modify Thy; Cyt and Gua are modified only under harsher conditions to as yet unidentified products. In the present study, denatured plasmid pCMV beta gal DNA was exposed to 0.015-1.5 mM KMnO4, pH 8.6, at 4 degrees C for 5 min, after which the DNA was hydrolyzed in formic acid, trimethylsilylated, and analyzed for modified base content by gas chromatography-mass spectrometry/selected ion monitoring. KMnO4 treatment, even at concentrations as low as 0.015 mM, caused a concentration-dependent increase in the Thy products Thy glycol and 5-hydroxy-5 methylhydantoin, the Cyt products Cyt glycol, 5,6-dihydroxycytosine, and 5 hydroxyhydantoin, the Ade product 8-hydroxyadenine, and the Gua product 8 hydroxyguanine. The Ade product 4,6-diamino-5-formamidopyrimidine and the Gua product 2,6-diamino-4-hydroxy-5-formamidopyrimidine were minimally (less than or equal to 2-fold) increased by treatment with greater than or equal to 0.8 mM KMnO4. These data demonstrate that, in addition to Thy, Cyt, Gua, and Ade bases in plasmid DNA may be modified by treatment with KMnO4, even under mild conditions. They represent the first identification of Cyt, Gua, and Ade products caused by KMnO4 treatment. Furthermore, these data suggest that previous studies which have used treatment with KMnO4 to study the mutagenicity of Thy glycol specifically or as a Thy-specific probe in DNA structure should be interpreted with caution. PMID- 2221921 TI - Inhibition of phosphoenolpyruvate carboxykinase from Trypanosoma (Schizotrypanum) cruzi epimastigotes by 3-mercaptopicolinic acid: in vitro and in vivo studies. AB - 3-mercaptopicolinic acid (3MP) was shown to be a powerful and specific inhibitor of the phosphoenolpyruvate carboxykinase (PEP-carboxykinase; ATP:oxyloacetate carboxylyase (transphosphorylating), EC 4.1.1.49) isolated and purified to homogeneity from Trypanosoma (Schizotrypanum) cruzi epimastigotes (Urbina, J. A., 1987, Arch. Biochem. Biophys. 258, 186-195). In the presence of saturating concentrations of the cosubstrates the inhibition was purely noncompetitive toward all substrates in the carboxylation reaction. The inhibition was specific to this enzyme, being nonexistent or moderate toward eight other enzymes tested that are involved in glycolysis, hexose monophosphate shunt, Krebs' cycle, and amino acid metabolism. These facts, together with the kinetic constants of the enzyme and the intracellular concentrations of its substrates, predicted a very potent inhibition of the reaction catalyzed by this enzyme in vivo. In accordance of this prediction 200 microM 3MP inhibited 2.2-fold the production of [2,2' 13C]succinate from D-[1-13C]glucose by intact epimastigotes under anaerobic conditions, as shown by 13C NMR and 1H NMR spectroscopy; correspondingly the overall glucose consumption rate decreased by the same factor, while the relative rate of production (per mole of glucose consumed) of the other main product of glucose catabolism, [3-13C]alanine, was increased 3-fold by the drug. Under aerobic conditions the glucose catabolism was faster (negative Pasteur effect) and the drug at the same concentration again blocked succinate production but had negligible effects on glucose consumption. On the other hand, 200 microM 3MP blocked completely the epimastigotes' catabolism of L-[U-14C]proline through the Kreb's cycle via PEP-carboxykinase, as indicated by the disappearance of 14C label present in alanine, pyruvate, citrate, and isocitrate after 1 h of incubation in the presence of the labeled amino acid, while the amount of radioactivity present in alpha-ketoglutarate and malate doubled. The results support the proposition that PEP-carboxykinase has a central role in the energy metabolism of this organism as it is essential for the catabolism of amino acids. PMID- 2221920 TI - Blood antioxidant status and erythrocyte lipid peroxidation following distance running. AB - The relationship between prolonged exercise, oxidative stress, and the protective capacity of the antioxidant defense system has been determined. Venous blood samples were removed from seven trained athletes before and up to 120 h after completion of a half-marathon for measurements of blood antioxidants, antioxidant enzymes, and indices of lipid peroxidation. Plasma creatine kinase (CK) activity, an index of muscle damage, increased (P less than 0.05) to a maximum 24 h after the race but this was not accompanied by changes in conjugated dienes and thiobarbituric acid reactive substances (TBARS), which are indices of lipid peroxidation. An increase (P less than 0.05) in plasma cholesterol concentration (4%) immediately after the race was similar to the change in plasma volume (6%). However, transient increases (P less than 0.05) immediately postrace in the plasma concentrations of uric acid (24%), vitamin A (18%), and vitamin C (34%) were only partly accounted for by the fluid shifts. The immediate postrace increases in alpha- and gamma-tocopherol did not attain statistical significance. Erythrocyte antioxidant enzyme activities were unaffected by the exercise but the alpha- and gamma-tocopherol concentrations progressively increased (P less than 0.001 and P less than 0.05, respectively) up to 48 h postrace. Paradoxically, 24 h after the race erythrocyte susceptibility to in vitro peroxidation was markedly elevated (P less than 0.01). This enhanced susceptibility to peroxidation was maintained even at 120 h postrace and did not correspond to changes in the age of the red cell population. A decrease (P less than 0.001) in total erythrocyte glutathione immediately after the half-marathon was mainly due to a reduction in the reduced form (GSH). The results show that when trained athletes run a comparatively short distance sufficient to result in some degree of muscle damage but which is insufficient to cause elevations in plasma indices of lipid peroxidation, significant alterations in erythrocyte antioxidant status do occur. PMID- 2221922 TI - [Regulation of the multidrug resistance (MDR)1 gene expression]. AB - MDR1 gene encodes a gp-170 membrane protein which acts as a energy-dependent pump to transport anticancer agents out of the cells. In this article, we briefly summarize the MDR gene family, gene amplification, gene expression by differentiation and gene expression in clinical tumors. We also describe the characterization of the promotor and tissue specific enhancer of the MDR1 gene and our recent study of the regulatory mechanism of this gene expression. PMID- 2221923 TI - [Alternating non-cross resistant multi-drug chemotherapy against malignant lymphoma (CAMBO-VIP)--consideration of the dose intensity]. AB - Dose intensity defined as the amount of drug used per unit time, expressed as mg/m2/week, was reported to be a significant determinant of antitumor activity of single or combined drugs in cancer chemotherapy. We formulated a 12 week high dose intensity chemotherapy (CAMBO-VIP) for the treatment of advanced non Hodgkin's lymphoma with aggressive histology. The treatment consists of weekly alternate administration of myelosuppressive and non-myelosuppressive agents. Doxorubicin was administered every other week in combination with either cyclophosphamide, etoposide or ifosfamide. On the weeks in between, non myelosuppressive vincristine was given with either methotrexate with leucovorin rescue or bleomycin. Prednisolone was given for the first and the last 4 weeks. Dose reduction and treatment delay were kept minimal for the purpose not lowering dose intensity. As of February 1990, 32 patients (pts), median age 52, entered the study, 29 of whom completed the treatment. There were 3 incomplete cases, in which 2 were due to interruption of the treatment at 5 and 6 weeks, respectively and 1 due to a half dose given because of the old age. CR was obtained in 29 pts (90.6%). Relapse occurred in 3 (10.4%) with the median follow-up of 12 months. Two year disease-free survival (DFS) was estimated to be 76.0% for all the patients and 83.9% for CR patients. Toxicity of CAMBO-VIP was moderate with no chemotherapeutic death. Myelosuppression was severe but of short duration, requiring virtually no dose reduction. Treatment delay was 3 days, median, and maximally 28 days. The average actual dose intensity calculated from given amount of drugs and treatment duration was as high as 90% of the protocol dose intensity. Dose intensity of CAMBO-VIP protocol is highest, equaling to that of MACOP-B, among representative series of reported lymphoma protocols. A highly significant correlation was observed between 9 drug relative dose intensity and DFS of the patients treated with each protocol. Significance of dose intensity as an independent prognostic factor, however, should be determined, by a prospective carefully designed stratified randomized studies. PMID- 2221924 TI - [Chemotherapy of thymoma]. AB - Thymoma is a low malignant, slow growing tumor and rarely metastasizes hematogenously or lymphogenously. Therefore, the local treatment by surgery or irradiation has been the main therapy for this tumor. In this paper, we reviewed the chemotherapy for thymoma in literature. Cis-platinum, doxorubicin, vincristine, cyclophosphamide and corticosteroid are mainly used by various dosages and various combinations. Papers concerning the chemotherapy for thymoma were reports of a single or a few cases. The chemotherapy is now effective for some kinds of malignant tumor. The chemotherapy for thymoma should be systematically studied. PMID- 2221925 TI - [MTT assay using fresh surgical specimens with reference to the transfer system and reproducibility in "test center" method]. AB - A chemosensitivity test (MTT assay) was conducted using 59 fresh surgical specimens collected from Keio University, Kitasato Institute Hospital and 14 affiliated hospitals, in order to assess the specimen transfer system and the reproducibility of the assay results obtained at Keio University and Kitasato Institute Hospital. Although the optical density yielded by the tumor cells in a number of 5 x 10(4)/well and the number of evaluable cases were significantly reduced through the transfer, the chemosensitivity pattern of the specimen was identical before and after the transfer. Fifty seven of 59 cases were evaluable and the concordant rate of the assay results between the two institutes was 80.6% (108/134) among each case-drug combination. Since the transfer system of the specimen was established and the reproducibility of the assay results in two institutes was confirmed, the "test center" method of the MTT assay appears to be possible by collecting the surgical specimens from the affiliated hospitals. PMID- 2221926 TI - [Antitumor activity of UFT against murine renal cell carcinoma: a study on the suppression tumor metastases]. AB - Experimental chemotherapy with UFT was performed against murine renal cell carcinoma (Renca) of spontaneous origin in BALB/c mice and the antitumor activity of UFT was compared with that of 5-FU. By oral administration started from the day after inoculation of Renca cells under the capsule of a kidney, the growth of tumor and formation of the spontaneous metastases to the lymph nodes, lung, spleen, and abdominal wall were inhibited significantly. The UFT or 5-FU treatment started on the 8th day after tumor inoculation also extended the survival time of the tumor-bearing mice and the anti-tumor effect of UFT was more marked than 5-FU. However, UFT treatment started on the 15th day did not prolong the survival time of Renca-bearing mice. From these results, UFT therapy seems to be beneficial for prevention of metastases after nephrectomy in the patients with renal cell carcinoma. PMID- 2221927 TI - [Investigation of UFT and radiation combination therapy of head and neck cancer- mainly in laryngeal cancer]. AB - We studied the effects of simultaneous combination therapy with UFT and radiation for 69 head and neck cases with the same protocol in 6 universities in Kanagawa. Completed cases (cases in which therapeutic effects could be evaluated) totaled 67 patients who could receive more than 40 Gy as a given radiation dose and more than 8.4 g as a total UFT dose. Responder rate at 90th day after completion of radiation in 67 completed cases (CR 57 cases + PR 6 cases/67 cases) was as favorable as 94%. A comparison between 52 cases of the most frequent laryngeal cancer and historical control 113 cases received single radiation therapy by means of Kaplan-Meier method resulted significantly (P less than 0.05) favorable in UFT combination group as for disease free rate in all cases, disease free rate in Stage IV cases, disease free rate in glottic cancer, and survival rate and disease free rate in supraglottic cancer. No severe adverse reactions were observed in all cases. This combination therapy with radiation and UFT was judged effective for head and neck cancer, especially laryngeal cancer. PMID- 2221928 TI - [Clinical results of UFT enteric-coated granule therapy under cooperative study (phase II study). Tokyo Cancer Chemotherapy Cooperative Study Group]. AB - We have carried out the Phase II study by oral administration of UFT enteric coated granules (UE) against various malignant tumors. Out of 45 patients entered in the study, 40 patients were evaluable: 36 patients among them had measurable lesions. PR (partial response) were obtained in two (11.1%) out of 18 patients with gastric cancer and one (50.0 %) out of 2 patients with lung cancer. Total response rate was 8.3%. Side effects by UE were slight; that is, anorexia (13.3%), nausea and vomiting (8.9%), generalized malaise (8.9%) and so forth. UE, as a long-term therapy, can be considered a useful drug against cancers with less side effects. PMID- 2221929 TI - [A comparative clinical trial of UFT medication and intravesical BCG in the recurrence of superficial bladder cancer. Study Group of UFT and BCG adjuvant therapy for bladder cancer]. AB - In sixty-four patients who had TUR-bt for superficial bladder cancer, the effect of intravesical BCG and UFT medication were compared. Group A (n = 20) were treated with BCG, group B (n = 22) were treated with UFT and group C (n = 22) were treated with both agents. The patients were followed up for more than 12 months by cystoscopy at a interval of 3 months, urinary cytology and bladder cold cup biopsy, if necessary. Thirteen of the 20 patients in group A and 13 of the 22 patients in group B were free of tumors, compared to 5 of the 22 patients in group C. Although the recurrence-free-rate in each group does not differ significantly, the combination therapy of intravesical BCG and UFT medication seems to decrease the rate of tumor recurrence for superficial bladder cancer. Side effects of BCG and UFT were tolerated well. PMID- 2221930 TI - [Septicemia in children with malignant disease]. AB - Severe infection is a major cause of morbidity and mortality in patients with malignancy. In this study, 34 episodes of septicemia occurred in 1,468 childhood patients with malignancy who admitted and were treated at National Sapporo Hospital between 1979 and 1988. The occurrence of septicemia and its mortality rate were higher in malignant hematologic disease than in malignant solid tumor. Most cases of septicemia occurred in relapse. The most frequent organism causing septicemia were Klebsiella pneumoniae (16.3%) and Staphylococcus epidermidis (16.3%). Septicemia due to Gram-negative organism was more frequent than that of Gram-positive organism or fungus. Polymicrobic septicemia occurred 3 times and multiple episodes 6 times. They had a high mortality rate. Neutropenia was strongly associated with episode of septicemia. In our series, absolute neutrophil count under 500 per microliter developed septicemia. Especially, children with less than 100 granulocytes per microliter had a major risk factor for the development of infection and death. No children with granulocyte count greater than 1000 per microliter died in connection with septicemia. PMID- 2221931 TI - [Studies on the mechanism of protective effect of selenium on nephrotoxicity of cis-diamminedichloroplatinum (CDDP) in mice]. AB - The mechanism of protective effect of sodium selenite (Se) on the nephrotoxicity of cis-diamminedichloroplatinum (CDDP) was studied with mice. CDDP and Se concentrations in the plasma, blood cell, kidney and liver were measured in mice given CDDP alone and those given both CDDP and Se. The nephrotoxicity of CDDP was observed in mice fed Se deficient diet (SDD). The activities of glutathione peroxidase (G-Px) in the plasma, blood cells, kidney and liver were measured in mice mentioned above. Co-administration of Se did not influence on the concentration of CDDP in the blood, kidney and liver. In mice fed SDD, the nephrotoxicity of CDDP increased and G-Px activities of the blood and kidney decreased. In mice given Se, G-Px activities was not increased. These results suggest that interaction between CDDP and Se differs from that between mercury and Se, or between cadmium and Se (formation of compound). Intake of Se is related to the appearance of the nephrotoxicity of CDDP. G-Px may be related partially to the protective effect of Se on the nephrotoxicity of CDDP. PMID- 2221932 TI - [A case of effective chemotherapy with CDDP and VDS for metastatic lesions of the lung and spleen and simultaneous resection]. AB - A case of 51-year-old woman, she was suffered from primary parotic cancer and the right parotic gland was resected in 1980, and pulmonary metastatic nodule was also operated in 1982. She was admitted in our institute with complaint of bloody sputum and cough in 1989, and diagnosed as pulmonary and splenic metastasis of parotic cancer. Two courses of combined chemotherapy, with CDDP by administration through bronchial artery, with CDDP and VDS by a systematic intravenous injection, was done. With these therapies, partial responses were obtained in the metastatic lesions, so spleen and left lower lobe of lung were resected. In the histological examination of the resected tumors, tumor cells were nearly disappeared, and we obtained Ef-2 effect according to the general rule for clinical and pathological record of lung cancer. She was discharged after one more chemotherapy and with no sign of recurrence now. We reported this case because of the possibility of the effective adjuvant therapy of the case with multiple lesions of cancer metastasis, and the rare case of splenic metastasis. PMID- 2221933 TI - [Single drug chemotherapy with 5-FU oral administration of bladder cancer]. AB - 58-year-old male with bladder cancer complicated acute myocardial infarction (aMI) were treated by 5-FU 300 mg/day orally for approximately one and a half months as single drug chemotherapy preoperatively. CT studies showed PR in bladder lesion and an improvement of bilateral hydronephrosis also. Biochemical evaluations as Thymidylate synthase inhibition and FdUMP were made on biopsy and operative specimens of urinary bladder. Clinical trials with 5-FU oral administration in bladder cancer were not held widely. Although its effectiveness and safety has been accepted in several fields. It was useful for a conservative operation case as single drug chemotherapy. PMID- 2221935 TI - Histopathologic spectrum of clinically atypical melanocytic nevi. II. Studies of nonfamilial melanoma. AB - We studied the clinically most atypical pigmented lesion removed from each of 142 patients with newly diagnosed sporadic melanoma. The specimens were categorized as to the type of nevus, ie, junctional or compound, presence of congenital features, and degree of nuclear atypicality--presence of nuclear enlargement, nuclear pleomorphism, hyperchromatism, and prominent nucleoli--of intraepidermal nevomelanocytes. The frequency of nuclear abnormality was graded as 1 (rare cells), 2 (10% to 50% of cells), or 3 (greater than 50% of cells) for each nuclear parameter. Among all lesions, 42 (29.6%) were junctional nevi, 74 (52.1%) were compound nevi, and 14 (9.9%) were dermal nevi. Eighteen percent of the total were either dysplastic nevi (23 cases) or malignant melanoma in situ (three cases). Fourteen nevi (9.9%) had congenital features. There were 12 junctional and 39 compound nevi and one dermal nevus that exhibited nuclear abnormality, but only four junctional nevi compared with 19 compound nevi had sufficient atypia for a designation of dysplastic nevus. Only two nevi with congenital features demonstrated any nuclear abnormality, and these were clearly nondysplastic. Thus, among nevi surgically removed as the clinically most atypical lesion in this study, compound nevi were much more likely to demonstrate nuclear atypia (and dysplasia) than were other nevi, ie, junctional or dermal nevi, or nevi with congenital features. PMID- 2221934 TI - Management of chronic photosensitive eczema. PMID- 2221936 TI - Ionizing radiation-induced pemphigus. Case presentations and literature review. AB - Reports of pemphigus following ionizing radiation exposure are rare. We report two cases and review the literature regarding this association. Characteristics common to these cases include a prodromal persistent nonspecific dermatitic eruption that is often interpreted as radiation dermatitis, and latency of variable duration before the onset of a vesiculobullous eruption that begins at the portal of irradiation. Direct immunofluorescence is positive for intercellular IgG, while indirect immunofluorescence is commonly positive only at low titers; HLA correlations have not been studied. Documentation of clinical course and laboratory confirmation of the diagnosis, including hematoxylin-eosin, direct and indirect immunofluorescence, and HLA determinations (if available), should be recorded to enable further clarification of this entity. PMID- 2221937 TI - Transfusion-associated graft-vs-host disease in patients with malignancies. Report of two cases and review of the literature. AB - Graft-vs-host disease can develop in immunosuppressed individuals who receive blood-product transfusions that contain immunocompetent lymphocytes. We report two cases of fatal transfusion-associated graft-vs-host disease that developed in patients with Hodgkin's disease who were undergoing therapy. We review all cases of this entity in patients with malignancies, represented predominantly by patients with hematologic malignancies. The groups at risk for development of transfusion-associated graft-vs-host disease, the clinical presentation and course, and methods of diagnosis are summarized. Prevention of this highly fatal condition is possible by irradiation of blood products given to patients at risk, but problems remain in determining the groups that warrant such measures. Dermatologists need to have heightened awareness of this entity to facilitate more complete diagnosis and allow establishment of effective standards of care. PMID- 2221938 TI - Compound blue nevus: a variant of blue nevus with an additional junctional dendritic component. A clinical, histopathologic, and immunohistochemical study of six cases. AB - We studied six cases of heavily pigmented melanocytic lesions with features of blue nevi within the dermis, but with an additional junctional dendritic component. This compound variant of blue nevus is an uncommon lesion that has not been previously identified as a distinct histologic entity. Immunoperoxidase staining for S100 protein and counterstaining with azure B distinguished the presence of melanocytes among numerous melanophages within the dermis. The compound variant of blue nevus can be distinguished histologically from combined blue nevus, pigmented spindle cell nevus, malignant melanoma, and melanosis due to a regressed malignant melanoma. The six lesions were from three men and three women whose ages ranged from 11 to 51 years (mean, 31 years). Three lesions were located on the trunk, two on the extremities, and one on the head. After a mean follow-up period of 47 months (range, 38 to 58 months), there was no evidence of recurrence. PMID- 2221939 TI - Severe phototoxic burn following celery ingestion. AB - A 65-year-old woman developed a severe, generalized phototoxic reaction following a visit to a suntan parlor. History taking revealed that she had consumed a large quantity of celery root (Apium graveolens) 1 hour earlier. With the use of thin layer chromatography, methoxsalen (8-methoxypsoralen) and 5-methoxypsoralen were identified in the extract from a similar celery root. The biologic activity of this extract, as evaluated with the semiquantitative Candida albicans inhibition technique, indicated a total psoralen dose of approximately 45 mg. Substantial amounts of psoralen may be absorbed from vegetables, such as celery, and under unusual circumstances, this may constitute a health hazard. PMID- 2221940 TI - Autoantibodies from patients with localized and generalized bullous pemphigoid immunoprecipitate the same 230-kd keratinocyte antigen. AB - Two patients demonstrating the typical clinical, histologic, and immunopathologic features of nonscarring localized bullous pemphigoid are described. These patients possess circulating IgG autoantibodies that bind the epidermal side of 1.0-mol/L sodium chloride-split human skin in indirect immunofluorescence microscopy. Immunnoprecipitation studies demonstrate that these patients have circulating autoantibodies that immunoprecipitate the same 230-kd bullous pemphigoid antigen that is precipitated by autoantibodies from patients with generalized bullous pemphigoid. These findings indicate that localized bullous pemphigoid is a true clinical variant of generalized pemphigoid rather than a separate nosologic entity. PMID- 2221942 TI - Vulvar erythema and induration. Extraintestinal Crohn's disease of the vulva. PMID- 2221941 TI - Blood transfusions and graft-vs-host disease. PMID- 2221943 TI - Vulvar erythema. Vulvitis chronica plasmacellularis (Zoon's vulvitis). PMID- 2221944 TI - A gray-brown discoloration of the penis. Malignant melanoma of the penis (MMP). PMID- 2221945 TI - Repeat direct immunofluorescence to discriminate pemphigoid from epidermolysis bullosa acquisita. PMID- 2221946 TI - Hello tricone; good-bye "dog-ear". PMID- 2221947 TI - Anti-single-stranded DNA antibody and muscle involvement in localized scleroderma. PMID- 2221948 TI - Dosage guidelines: extracorporeal photochemotherapy (photopheresis) PMID- 2221949 TI - Fibrous papule and intradermal nevus. PMID- 2221951 TI - Androgenetic alopecia. PMID- 2221950 TI - Granuloma annulare and gold therapy. PMID- 2221952 TI - Acral persistent papular mucinosis: a peculiar variant of the discrete papular form of lichen myxedematosus. PMID- 2221953 TI - The nail fold in pemphigus vulgaris. PMID- 2221954 TI - Urticaria pigmentosa in monozygotic twins. PMID- 2221955 TI - Fournier's gangrene: the human counterpart of the local Shwartzman phenomenon? PMID- 2221956 TI - Examinations in paediatric training. PMID- 2221957 TI - Senior house officer posts in community paediatrics--an introduction to child health. PMID- 2221958 TI - Growth failure secondary to moyamoya syndrome. PMID- 2221959 TI - Management of infantile gastroenteritis. PMID- 2221960 TI - Use of hearing aids in infancy. PMID- 2221961 TI - Phenobarbitone and febrile convulsions. PMID- 2221962 TI - Magnetic resonance imaging in neurological disorders. AB - To investigate the role of magnetic resonance imaging (MRI) in neurological disorders, 115 children were studied in two groups. Group A (78 patients) was studied by paired computed tomography and MRI cranial scans. Group B (37 patients) was studied by paired computed tomography assisted myelography (CTM) and MRI spinal scans. In group A, the scans were generally equivalent for supratentorial tumours and for investigating fits, hydrocephalus, benign intracranial hypertension, and cerebral atrophies, but MRI scanning was superior for posterior fossa tumours and cysts. In group B, MRI scans were superior for intramedullary spinal tumours, spinal dysraphic problems with tethering or syrinx, and were complementary to CTM in diastematomyelia. PMID- 2221963 TI - Slow release carbamazepine in treatment of poorly controlled seizures. AB - Thirty three children with poorly controlled epilepsy, and six new patients, were treated with slow release carbamazepine. Twelve of the former had a reduction in the number of seizures of more than half, and 10 had fewer side effects. Three of the new patients stopped having seizures. Variations in plasma concentrations between doses was significantly less when patients took the slow release preparation (22%) compared with the standard preparation (41%). Slow release carbamazepine may improve the conditions of children whose seizures are poorly controlled. PMID- 2221964 TI - Acute gastroenteritis in infants under 6 months old. AB - Sixty two babies under the age of 6 months who were admitted with gastroenteritis completed a study of gradual refeeding compared with abrupt refeeding after a period of rehydration. There was no difference in the incidence of recurrence of diarrhoea due to lactose intolerance, effect on weight, or duration of hospital stay. Twenty six babies (42%) had recurrence of diarrhoea after refeeding, all of whom settled with the introduction of a lactose free soya based formula. Well nourished babies under 6 months of age with mild to moderately severe gastroenteritis can be fed immediately with full strength milk feeds after rehydration. The introduction of a lactose free soya based preparation may provide an alternative to repeated attempts at regrading with cows' milk feeds in those patients with lactose intolerance. PMID- 2221965 TI - Management of gastroenteritis. AB - Childhood gastroenteritis remains a common reason for admission to British paediatric units, although the severity of the disease appears to be diminishing in recent years. We studied 215 infants and children with gastroenteritis admitted consecutively to four paediatric units in South Wales in order to determine the severity of the disease, the organisms isolated, the frequency of complications, and the adequacy of management before admission. Stool pathogens were isolated in 125 (58%) patients (viruses in 65, bacteria in 30, and protozoa in 19, with multiple infection found in 11). There was a low incidence of morbidity and complications, but prolonged diarrhoea (postenteritis syndrome) was present in 24 (11%) cases and 77 (36%) had received inappropriate treatment before admission. Contemporary gastroenteritis is thus a relatively mild disease in the acute phase, but management before admission to hospital is often inadequate, and prolonged diarrhoea may be a feature in a considerable number of cases. PMID- 2221966 TI - Prognosis of chronic granulomatous disease. AB - The records of 28 patients with chronic granulomatous disease born over a 32 year period were reviewed. The characteristics of the group, and the frequency with which various clinical and laboratory features had been recorded, was assessed. Nine patients were known to have died, in most cases of progressive suppurative infection. Actuarial analysis showed 50% survival through the third decade of life. The long term survival of patients developing symptoms after the end of the first year of life was significantly better than that of patients whose illness started in infancy. Our data confirm that the severity of chronic granulomatous disease is not uniform, and that the prognosis for long term survival is better than that suggested in earlier reports. Early onset may be a poor prognostic sign and invasive aspergillosis is a life threatening complication. In the absence of curative treatment, trials to assess the effectiveness of interferon gamma are necessary and early antenatal diagnosis should be offered to as many affected families as possible. PMID- 2221967 TI - Latent sensitisation to respiratory syncytial virus during acute bronchiolitis and lung function after recovery. AB - To determine whether latent sensitivity to respiratory syncytial virus antigen(s) occurs after infection, 27 infants with acute bronchiolitis were studied and compared with 15 hospital controls. Blood was collected for whole blood challenge, and histamine release was measured by a high performance liquid chromatography technique with fluorometric detection. There was a significantly greater histamine release to respiratory syncytial virus antigen(s) in those with bronchiolitis than in controls, expressed either in amount (median 154 nmol/l compared with 104 nmol/l) or percentage release (median 20% compared with 3%). There was a significant difference between index and control groups in terms of individual histamine responses. These findings strongly suggest that infants develop latent sensitivity to respiratory syncytial virus antigen(s) during the course of acute bronchiolitis. Serial lung function tests were performed in 15 infants. All infants had abnormalities of lung function at some stage, but the small numbers of subjects precluded comparison between 'sensitised' and 'non sensitised' infants. Further study is indicated to define the relation of latent sensitisation and subsequent bronchial hyper-responsiveness after respiratory syncytial virus infection in infants. PMID- 2221968 TI - Recurrent cyanotic episodes with severe arterial hypoxaemia and intrapulmonary shunting: a mechanism for sudden death. AB - The pathophysiology of recurrent cyanotic episodes has been investigated in 51 infants and children. Episodes began at a median age of 7 weeks (range 1 day to 22 months, 39 at less than 4 months). They were characterised by the rapidity of onset and progression of severe hypoxaemia with early loss of consciousness from cerebral hypoxia. The most common precipitating factor was a sudden naturally occurring stimulus from pain, fear, or anger. In uncontrolled trials, cyanotic episodes were reduced in frequency and severity by tetrabenazine (n = 15) and additional inspired oxygen (n = 10). Eight patients died suddenly and unexpectedly (four during cyanotic episodes). Twenty eight patients underwent physiological studies during cyanotic episodes. There was no evidence of seizure activity at the onset and although prolonged absence of inspiratory effort with continued expiratory efforts was common, breathing sometimes continued. Episodes were not caused by upper airway obstruction and sometimes occurred during positive airway pressure ventilation. The rapidity of fall in arterial oxygen pressure and continued breathing suggested a right to left shunt of sudden onset. The results of contrast echocardiography and lung imaging studies confirmed that this was occurring within the lungs. These cyanotic episodes included both intrapulmonary shunting and prolonged expiratory apnoea. They are best explained by interactions between central sympathetic activity, brainstem control of respiration and vasomotor activity, reflexes arising from around and within the respiratory tract, and the matching of ventilation to perfusion in the lungs. They are a cause of sudden unexpected death in infancy and early childhood. PMID- 2221969 TI - Natural and modified history of complete atrioventricular septal defect--a 17 year study. AB - We reviewed 103 cases of isolated complete atrioventricular septal defect. These cases represented 4.4% of the cases of congenital heart disease diagnosed in our hospital by catheterisation and angiography during 1971-88. Most children (n = 76) had Down's syndrome. Banding of the pulmonary artery was performed in seven cases and complete repair in 67 cases. In the period 1971-82 the complete correction was performed at a mean age of 23 months with a surgical mortality of 88.8%. In the period 1983-8 the mean age at complete correction was 13 months, the mortality 43.2%, and the five year actuarial survival was 46.8%. The 22 patients that survived after complete correction were in functional classes I and II of the New York Heart Association classification. After a mean follow up of 10 years only eight (36%) of the 22 who were followed up and treated medically survived; all had developed pulmonary vascular obstructive disease and were in functional classes III or IV. Our findings stress the importance of early complete surgical repair. PMID- 2221970 TI - Pharmacokinetics of paracetamol after cardiac surgery. AB - Plasma concentration was measured after rectal and nasogastric administration of paracetamol 15 mg/kg to 28 febrile children aged between 9 days to 7 years who had undergone cardiac surgery. After equivalent doses, rectal administration in neonates and children on the first postoperative day was found to produce plasma concentrations below the therapeutic range with higher concentrations after nasogastric paracetamol on the second postoperative day. There was less variance in plasma paracetamol concentrations in neonates. Both plasma elimination half life and area under the plasma concentration time curve were significantly increased in neonates after suppository dosing compared with older children. There was no difference in antipyretic effect between the two routes of administration, but this was much lower than that previously reported in febrile children. PMID- 2221972 TI - Social integration of the older thalassaemic patient. AB - Because social policy favours the fullest possible social integration of chronically ill patients, we have evaluated the facilities that are needed to achieve this for patients with beta thalassaemia major in the light of the therapeutic advances that now permit them to survive into adulthood. We have investigated the social integration of adolescent and young adult thalassaemic patients, 171 from Greece and 112 from Ferrara in Italy. Patients in both areas show a good level of social integration and favourable self image, indicating what may be achieved by providing psychosocial support as part of a comprehensive approach to treatment. PMID- 2221971 TI - Plasma prolactin and clinical outcome in preterm infants. AB - Plasma prolactin was measured weekly in 280 preterm infants. The complex gestational age dependent pattern of postnatal prolactin release has been defined and reference standards provided. Plasma prolactin was higher in girls, with increasing divergence between the sexes from the third week onwards, and higher after two weeks, in infants of mothers with pregnancy related hypertension. Diet, assigned randomly, exerted a major effect on plasma prolactin, with significantly higher values in infants fed donor breast milk or standard formula than in those fed a protein, energy, and mineral enriched preterm formula. After adjusting for confounding factors, infants with the lowest plasma prolactin concentrations (less than 1000 mU/l, 32.9 micrograms/l) occurring usually at a nadir between days 5 and 12, showed a 120% increase in the duration of ventilatory assistance required, a 20% increase in the number of days to attain full enteral feeds, and a 30% decrease in length gain. We suggest preterm birth disrupts the normal perinatal pattern of prolactin release and that those infants who develop relatively low plasma concentration have an adverse outcome. Our data add to the broader debate on whether preterm infants require multiple endocrine replacement treatment. PMID- 2221973 TI - The iris in Williams syndrome. AB - Forty three children with Williams syndrome and 124 control subjects had their eyes photographed. The photographs were examined by three ophthalmologists and four geneticists of varying experience. A stellate pattern was noted more often in the irides of patients with Williams syndrome (51%) than in those of the control subjects (12%), and was more difficult to detect, or was absent, in heavily pigmented irides. We conclude that the stellate pattern is of diagnostic importance, particularly if the pattern is carefully defined and the clinician is experienced. PMID- 2221974 TI - Perforated duodenal ulcer: an unusual complication of gastroenteritis. AB - A 7 year old boy was admitted to hospital with gastroenteritis, which was complicated by an acute perforated duodenal ulcer. After oversewing of the perforation he made an uncomplicated recovery. Peptic ulceration is under diagnosed in childhood and this leads to delay in diagnosis and appropriate management. Ulceration is associated with severe illness and viral infections, but perforation is rare. PMID- 2221975 TI - An unusual cause of thoracic mass. AB - A previously well 10 year old boy presented with scoliosis, a mass in the chest wall, and a pleural effusion. Chest radiography showed the triad of chronic consolidation, pleural effusion, and rib periostitis. Investigations confirmed thoracic actinomycosis. Tissue spread was evaluated by computed tomography. It was successfully treated with benzylpenicillin, which was later replaced by clindamycin. PMID- 2221976 TI - Spontaneous resolution of congenital nephrotic syndrome in a neonate. AB - An infant with congenital nephrotic syndrome recovered spontaneously and completely by the age of 11 days and had remained well at the age of 1 year. This reinforces the view that reversible congenital nephrotic syndrome does occur and that it is not a single disease with a universally dismal prognosis. PMID- 2221977 TI - Congenital diaphragmatic hernia: impact of prostanoids in the perioperative period. AB - A prospective study of 10 neonates with congenital diaphragmatic hernia and five controls to determine the importance of prostanoid concentrations perioperatively and the relation with persistent pulmonary hypertension (PPH) is reported. In neonates with congenital diaphragmatic hernia postoperative concentrations of the vasoconstrictor thromboxane B2 rose significantly and were higher during episodes of PPH; this rise may provoke PPH and subsequent right to left shunting. PMID- 2221978 TI - Reflux vomiting. PMID- 2221979 TI - Elastic properties of human skin: relation to age, sex, and anatomical region. AB - Using a recently developed noninvasive, in vivo suction device for measuring skin elasticity, we evaluated age, sex, and regional differences in the viscoelastic properties of skin. A total of 33 volunteers participated in the study consisting of (a) 8 young females, (b) 9 old females, (c) 8 young males and (d) 8 old males. Measurements were performed on 11 anatomical regions; three different loads were applied: 100, 200, and 500 mbar. The parameters used were: immediate distension (Ue); delayed distension (Uv); immediate retraction (Ur); and, final deformation (Uf). To compare between subjects and anatomical regions, relative parameters independent of skin thickness were calculated: Uv/Ue, the ratio between the viscoelastic properties of skin and immediate distension, and Ur/Uf, which measures the ability of the skin to regain its initial position after deformation. Generally, Uv/Ue increased while Ur/Uf decreased with aging. Responses were variable with respect to load applied. Variability within anatomical regions was also noted. However, differences between the sexes were not statistically significant for most regions. These findings are in congruence with earlier studies suggesting the differences are mainly attributable to alterations in the elastic fiber network. This procedure provides a simple, quantitative assessment of elastic properties of the skin. Its application may help in future investigations of other connective tissue disorders. PMID- 2221980 TI - UVA-induced tumours in pigmented hairless mice and the carcinogenic risks of tanning with UVA. AB - An animal experiment is presented in which two groups of pigmented hairless mice were exposed daily to suberythemal doses of UVA to study tumourigenesis. The aim of the study was to estimate the carcinogenic risks of tanning by UVA. The pigmented hairless mice, Skh-hr2, were separated by selective breeding into two groups, the "browns" and the "blacks". Both groups were exposed daily to UVA from fluorescent UVA lamps (Philips TL40W/09) purified by rigorously filtering out the shorter wavelengths. No acute actinic damage was observed after any exposure. However, in most UVA exposed animals, especially in the blacks, a marked scratching preceded the development of tumours. Hyperkeratosis was also observed. All animals developed tumours. Histopathologically at least 60% of the tumours were squamous cell carcinomas. Depositions of melanophages were observed, but no melanomas. It is beyond any doubt that UVA is carcinogenic in laboratory animals. The present state of knowledge justifies no preference for tanning with UVA over tanning with UVB. PMID- 2221981 TI - IgE-positive epidermal Langerhans cells in allergic contact dermatitis lesions provoked in patients with atopic dermatitis. AB - To see whether or not IgE-bearing epidermal Langerhans cells are specific to skin lesions of atopic dermatitis (AD), we performed immunohistochemical and immunoelectron microscopic examinations of dinitro-chlorobenzene (DNCB) contact dermatitis lesions provoked in uninvolved skin of eight patients with AD. In all of the eight examined, IgE-positive epidermal Langerhans cells were observed in the DNCB dermatitis lesions. Typical staining of anti-IgE was absent in the epidermis of normal-appearing skin of five patients with AD. Thus, it is likely that IgE positive epidermal Langerhans cells non-specifically occur in different eczematous diseases provoked in patients with AD. PMID- 2221982 TI - Desmosomes, corneosomes and desquamation. An ultrastructural study of adult pig epidermis. AB - We recently developed a pig skin model to determine the role of corneosomes (modified desmosomes in the stratum corneum) and extracellular lipids in desquamation. The present study provides control morphometric data on the morphological changes in desmosomes and corneosomes leading to desquamation in adult pig epidermis in vivo. The extracellular space within desmosomes gradually widened from the basal to the granular layer, and decreased slightly in the stratum corneum. Mid-dense line broadening, and increased electron density of the distal light layers, coincided with membrane-coating granule extrusion in the outer granular layer. Corneocyte attachment correlated with corneosome distribution. Compactum packing was relatively tight and corneosomes were numerous. Cohesion was mainly peripheral in the disjunctum, and corneosomes were restricted to corneocyte edges. Adhesion had a tongue-and-groove appearance with corneosomes riveting corneocyte peripheries into a lipped groove on adjoining cells. Cells shed by peeling radially towards the lipped groove, and corneosomes decreased from lower to upper disjunctum. Corneosome breakdown commenced with an electron lucent band forming between the plug and lipid envelope. The plug was then unzipped from the lipid envelope and degraded. Corneosomes did not form squamosomes. PMID- 2221984 TI - Lactate dehydrogenase release as an indicator of dithranol-induced membrane injury in cultured human keratinocytes. A time profile study. AB - HaCaT cells, a rapidly multiplying human keratinocyte line, were tested for their sensitivity to antipsoriatic dithranol with regard to classical proliferation parameters and for the drug's action on the plasma membrane integrity by the dose and time-dependent release of cytosolic lactate dehydrogenase (LDH). In the case of 3H thymidine as well as 14C amino acid incorporation the 50% inhibition concentration (IC50) was 0.2 microM dithranol 24 h after initial exposure to the drug. For protein content of attached cells the IC50 proved to be greater than 3.0 microM. Using 0.3, 1.0 and 3.0 microM dithranol, significant (p less than 0.05) dose dependent LDH release of 0.866 +/- 0.387, 1.842 +/- 1.127 and 2.938 +/ 1.635 mU per hour and cm2 confluent culture area was measured between the 5th and the 24th hour, compared to an acetone control of 0.504 +/- 0.299 mU/h x cm2. Between the 2nd and the 4th hour as well as from the 25th to the 48th hour and the 49th to the 72nd hour the LDH release after dithranol treatment did not exceed the control value. In accordance with these findings dose-dependent morphological signs of cell injury were detected by phase contrast microscopy beyond the 4th hour. The data reveal that: HaCaT cells are a very sensitive target for the antiproliferative action of dithranol; the drug causes considerable plasma membrane damage even at concentrations as low as 0.3 microM; and this membrane damage becomes evident after a latency of at least 4 h and for a limited period of up to 24 h. PMID- 2221983 TI - Immunohistological evaluation of basal cell carcinoma immunoinfiltrate during intralesional treatment with alpha 2-interferon. AB - We investigated the peritumoral and intratumoral immune infiltrate in 6 basal cell carcinomas (BCCs) treated with recombinant alpha 2b-interferon. Each BCC was injected intralesionally three times a week for 3 weeks with 1.5 x 10(6) IU of interferon per injection (total dose 13.5 x 10(6) IU). The immunohistological study was done before the start of interferon therapy and 15 days afterwards, using a series of monoclonal antibodies and an immunocytochemical technique. Before therapy the infiltrate consisted mainly of CD3+ (T) cells, with prevalence of CD4+ (helper/inducer) T cells. The percentage of T cells expressing interleukin-2 receptor (CD25+ cells) was higher in the tumor nests than in the peritumoral infiltrate (20% and 11% respectively). CD1+ (Langerhans) cells and CD14b+ cells (monocytes/macrophages) were present in the peritumoral infiltrate in all cases (9% +/- 5% and 14% +/- 7% respectively). Very few CD56+ (natural killer), CD15+ (granulocytes) and CD20+ (B) cells were observed in the peritumoral infiltrate and none at all in tumor nests. After 15 days of interferon therapy, we observed an increase in peritumoral and intratumoral CD4+ cells. There was a decrease in the number of CD25+ cells and of CD1+ cells in the peritumoral infiltrate. The number of intratumoral CD25+ increased. No variations were seen in CD14b, CD15, CD20, and CD56 positive cells. Eight weeks after completion of therapy, two BCCs were cleared and the remaining four showed clinical and histological improvement. These results may indicate a direct effect of interferon against BCC; in addition the immunohistological findings suggest that intralesional interferon enhances T cell mediated immune response, especially in tumor nests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2221985 TI - Growth advantage by overexpression of normal Harvey ras proto-oncogene in cultured rat epidermal keratinocytes. AB - The ras proto-oncogene is frequently amplified and overexpressed in the hyperproliferative conditions of epidermal keratinocytes. To investigate the effects of its overexpression on the growth of keratinocytes in a model system, we constructed expression vectors for normal human Ha-ras and introduced them into FRSK cells, a fetal rat epidermal keratinocyte cell line. Several clones containing the transfected Ha-ras were isolated, and two of them overexpressed this gene. In these clones DNA synthesis and cell growth were greater than in other clones expressing this gene at low levels. Thus we suggest that overexpression of normal ras gene may provide growth advantage to epidermal keratinocytes. PMID- 2221986 TI - Sphingoglycolipids in human cultured keratinocytes. PMID- 2221987 TI - Inflammatory mediators are involved in the Candida albicans killing activity of human epidermal cells. PMID- 2221988 TI - Effects of Sandimmun on T lymphocyte and dendritic cell subpopulations in psoriasis. PMID- 2221989 TI - The effect of fibrin glue and peritoneal grafts in the prevention of intraperitoneal adhesions. AB - We studied the effect of fibrin sealant and peritoneal grafts applied by fibrin glue on adhesion formation in the rat. Sealing and patching of ischaemic lesions of the uterus resulted in a significant increase in adhesion formation. We conclude, that fibrin sealant and peritoneal grafts can not be given general approval for prophylaxis of intraperitoneal adhesions. PMID- 2221990 TI - Plasma and erythrocyte zinc and birth weight in pre-eclamptic pregnancies. AB - Plasma and erythrocyte zinc concentrations in 45 proteinuric pre-eclamptic Chinese women were measured. There was no difference in either the plasma or erythrocyte zinc concentration between pre-eclamptic patients with and without intrauterine growth retardation. There was no correlation between either plasma or erythrocyte zinc concentration with the gestation at delivery, birth weight, mean arterial pressure and plasma albumin concentration. On the other hand, both plasma albumin concentration and mean arterial pressure were significantly correlated to birth weight, and the mean arterial pressure was also significantly higher in patients with intrauterine growth retardation. Plasma and erythrocyte zinc are not useful as indices of severity in pre-eclampsia. PMID- 2221991 TI - Fructosamine in relation to maternofetal glucose and insulin homeostasis in gestational diabetes. AB - The problem in screening for gestational diabetes is recognizing fetuses endangered by hyperinsulinism. 21.8% of patients with gestational diabetes (defined as a glucose peak exceeding 160 mg/dl after an oral glucose load of 1 g per kg body weight) develop fetal hyperinsulinism. Thus, is indicated by an elevated amniotic fluid insulin (AFI) concentration and requires insulin treatment. Since fetal hyperinsulinism can be neither predicted nor ruled out by single parameters of maternal metabolism, every patient with gestational diabetes had to undergo amniocentesis for amniotic fluid analysis. In 110 gestational diabetics and 822 controls, fetal hyperinsulinism was predicted by the combination of the oGTT (greater than or equal to 160 mg/dl) and maternal serum fructosamine (greater than or equal to 2.6 mmol/l) with a sensitivity of 95.8% and a specificity of 91.8%. Thus, 73% of gestational diabetics need not undergo amniocentesis. With a sensitivity of 20.8%, the combination of the oGTT and HbA1c is not useful in identifying hyperinsulinemic fetuses. PMID- 2221992 TI - The grand multipara--still an obstetrical challenge? AB - To study whether grand multiparity (parity of 6 or more) still carries risk, we studied two birth cohorts in northern Finland: the first comprised 12,231 births to 12,068 mothers in 1966 and the second comprised 9478 births to 9362 mothers in 1985/86. The percentage of grand multipara decreased from 7.7 to 4.0. The grand multipara made fewer antenatal visits than the others. The proportion of grand multipara referred to maternity outpatient clinics of hospitals was smaller, but the mean number of visits was higher than of lower parity women. The mean number of admissions to hospital was similar in both groups but grand multipara stayed longer in hospital, smoked less (4.3% vs. 22.7%) and had a higher incidence of essential hypertension than women of lower parity. The grand multipara had fewer caesarean sections (7.5% vs. 14.1%) and vacuum extractions (0.5% vs. 5.1%) but more inductions of labour (33.1% vs. 23.5%) than mothers of lower parity. The number of low birth weight (LBW) infants (less than 2500 grams), stillbirths and neonatal deaths (before 28 days) was significantly lower in 1985/86 than in 1966 in women of lower parity but there was no such change in grand multipara. However, the percentage of LBW infants was smaller among grand multipara than among women of lower parity in both cohorts (2.7% vs. 4.1%, NS). The stillbirth plus neonatal death rate in grand multipara was higher than in women of lower parity (1.9% vs. 0.9%, P less than 0.05) partly because of a higher incidence of major congenital anomalies. PMID- 2221993 TI - Screening for gestational diabetes among women who have previously had a large baby or a stillborn infant. AB - In Baranya county, Hungary oral glucose tolerance tests were done according to WHO recommendations in pregnant women with a history of a previous baby weighing greater than or equal to 4000 g and/or a previous unexplained intrauterine fetal death. The first oral glucose tolerance test was done at 16-20 weeks gestation, and it was repeated monthly if it was normal. Patients with impaired glucose tolerance or gestational diabetes were treated by diet and/or insulin. 152 patients were involved in the screening program. Twenty-six of 81 patients had a "lag" curve blood glucose still above 5.5 mmol/ at 180 min. PMID- 2221994 TI - Androgen receptors, serum androgen levels and survival of breast cancer patients. AB - Steroid receptor levels and serum androgen levels were determined in 61 breast cancer patients and 34 patients with non-malignant breast lesions. Testosterone and dehydroepiandrosterone-sulfate did not and androstenedione did show a difference between the two groups. Androgen levels had no influence on survival rates. Androgen receptor (AR) levels correlated with progesterone receptor levels, but not with estrogen receptor levels or with tumor stage. Patients with positive AR findings had a better survival rate; this was independent of tumor stage. AR findings may therefore be a prognostic index in breast cancer patients. PMID- 2221995 TI - Acute urinary retention caused by a unilateral hematometra. AB - We describe a unilateral hematometra with an associated hematosalpinx causing acute retention of urine in a female adolescent. Normal menstruation had occurred from the uterine cavity on the unaffected side. Treatment was by abdominal metroplasty with complete excision of the uterine septum and a terminal cuff salpingostomy. Urological investigation revealed ipsilateral renal agenesis. PMID- 2221996 TI - Pancytopenia in a patient given pyrimethamine and sulphamethoxidiazine during pregnancy. AB - This is a report of a pregnant woman who became pancytopenic in the second trimester following pyrimethamine administration. The patient recovered on steroid, antibiotics, transfusion, folic acid and folinic acid therapy, and the pregnancy was uneventful afterwards. The patient was delivered of a healthy term infant. PMID- 2221997 TI - [In situ hybridization: principles, methods and applications]. AB - In situ hybridization is used to localize DNA or RNA sequences in tissue sections, single cells or chromosome preparations. The preparation and labeling of probes and the main steps of the technique are described and discussed together with its main applications. PMID- 2221998 TI - [Mucocutaneous leishmaniasis. Histologic classification and anatomoclinical correlations. Apropos of 102 cases]. AB - Two hundred and three skin and mucosal biopsies performed in 162 patients suffering from leishmaniasis, were studied retrospectively. They were classified according to Ridley into 5 histological groups of increasing severity. In cutaneous leishmaniasis, a high proportion of the biopsies belonged to groups III and IV. In mucocutaneous leishmaniasis, the percentage of groups III and VI was lower and group V was present in 20% of cases. In 16 patients, followed by repeated biopsies, we detected some variations of the histological group during the course of the disease. However, there were no positive correlations between clinicopathological features and prognosis. PMID- 2221999 TI - [Thyroid microcarcinoma with a fatal outcome and 34 other unusually aggressive cases reported in the literature]. AB - A follicular thyroid microcarcinoma was revealed by scapular metastases. Despite treatment, other metastases were the cause of death after a course of 14 years. In the medical literature there are at least thirty-four other examples of follicular or papillary carcinoma of less than 15 mm (previously called occult) that have either given rise to blood-born metastases or have been the cause of death. Present data from light and electron microscopy, immunohistochemistry and microspectrophotometry cannot differentiate between small and large carcinomas. Microcarcinomas (particularly papillary ones) are frequent in the general population and are found in 5% of thyroids. They are usually not aggressive. Those which show vascular or capsular invasion, a lack of lymphoid infiltrate and large cervical lymph node metastases are more likely to have an unfavorable course. The discovery of a microcarcinoma in a thyroid cells for an extended follow-up. PMID- 2222000 TI - [Adult type rhabdomyoma of the soft palate: pathology of 2 cases with review of the medical literature]. AB - In this paper, the authors report two cases of adult type rhabdomyomas of the soft palate. This tumor is composed of striated muscle cells containing striations and intracytoplasmic rod-shaped inclusions. In specimens already fixed in aqueous fixators (formalin...), some tumor cells presented a fixation artefact and displayed the morphology of so-called "spiderweb cells". Adult type rhabdomyoma is a real tumor. Total surgical removal is sufficient to cure the patient of this tumor in most cases. PMID- 2222001 TI - Primary vascular bone sarcomas. A clinicopathological and immunohistochemical study of two cases. AB - Two cases of primary vascular bone sarcomas are reported. The first case presented a rather slow clinical course and a non-aggressive histological picture and was classified as hemangioendothelioma. The second was a frankly malignant tumor, already metastatic at the time of diagnosis, which was classified as angiosarcoma. Views concerning the nomenclature and the behavior of primary vascular bone sarcomas are also discussed. PMID- 2222002 TI - Malignant melanoma of the gallbladder. Case report and review of the literature. AB - The authors are presenting a new case of malignant melanoma of the gallbladder to be added to those described in the literature. The tumour appeared as a polypoid mass of the gallbladder and had metastasized to the jejunum and the brain. Review of the literature and analysis of this case require a thorough discussion of the real existence of tumours in this unusual primary site. PMID- 2222003 TI - [Cardiac pathology in human immunodeficiency virus infection]. AB - Clinical cardiac manifestations are rare in the course of acquired immunodeficiency syndrome (AIDS), but cardiac lesions can be found at autopsy in 60% of cases. Myocardium and pericardium are the most frequently involved. Cardiac involvement in opportunistic infections, Kaposi's sarcoma, and non Hodgkin's malignant lymphomas usually reflects systemic dissemination of the disease. Idiopathic myocarditis and hypertrophic cardiomyopathy may also occur and may be related to human immunodeficiency virus. Dysautonomia and drug-induced cardiac lesions have also been reported. Cardiac involvement of acquired immunodeficiency syndrome in children is characterized by possible lesions of conduction tissue. PMID- 2222004 TI - Hydatidosis in Belgium: analysis of larval Echinococcus granulosus by SDS-PAGE and western blotting. AB - Echinococcosis/hydatidosis is characterized by the existence of various strains of the parasite Echinococcus granulosus. In order to study the degree of variability in Belgium, protoscoleces (PS) were isolated from infected intermediate hosts (horse, cattle, pig, goat and man). Homogenate supernatants of these PS were compared by SDS-polyacrylamide gel electrophoresis and western blotting: 15 to 26 predominantly silver staining bands (depending on the source of the parasites), were selected to study existing homologies among these possible strains. Antisera raised against PS homogenates of horse, cattle, pig and goat origin, were used to compare antigenicity by western blotting. The results indicate a closer similarity between E. granulosus of horse, goat and pig origin whereas E. granulosus derived from cattle showed less homology with any of the former. Results are discussed against the background of the occurrence of E. granulosus in Belgium. PMID- 2222005 TI - Characterization of a Trichinella isolate from polar bear. AB - An isolate of Trichinella of polar bear origin was studied by isoenzymatic typing. It was found referable to Trichinella nativa. While the Wistar rats proved nearly refractory to this isolate, the Swiss albino mice were highly susceptible. Ninety-one per cent of the cystic lesions in the diaphragm of the polar bear contained viable larvae after over 20 years of acquisition of the infection by the host which is a case of extreme adaptability of the parasite to its host. The anatomo-pathological aspects of these lesions are studied and the zoonotic significance of this isolate examined. PMID- 2222006 TI - [Evaluation of practice and costs of vector control on a family level in Central Africa. II. Douala City (Cameroon), July 1988]. AB - A Knowledge, Attitude, Practice survey was carried out in July 1988 in Douala city, by cluster sampling and household visits. 98% of these households declared being disturbed by mosquitoes (bites, diseases, noise); 91% of families are using a vector control method; the main methods are: bed-nets (48%), insecticide sprays (39.5%) and mosquito coils (36.7%). The average cumulated expense by households for vector control (116.6 ECU/year) and care for diseases attributed to mosquitoes (147.4 ECU/year) was evaluated at the equivalent of about 3 months of "minimum monthly wages". More than 90% of people interviewed would accept buying and using an insecticide impregnated bed-net provided that the price of such a product be lower than the current habitual price for ordinary bed-nets. The distribution of the impregnation technique must be made at the level of impregnation centres, which should start impregnating the existing bed-nets and take care of informing the public. PMID- 2222007 TI - The effect of intersubspecific hybridization and gamma radiation on the reproductive biology of Glossina palpalis palpalis (Robineau-Desvoidy) and Glossina palpalis gambiensis Vanderplank. AB - The closely related tsetse fly subspecies Glossina palpalis palpalis (Nigeria origin) and Glossina palpalis gambiensis (Burkina Faso origin) hybridize readily in the laboratory. Hybridized G.p.palpalis females produced less offspring than the parental intrasubspecific crosses. Adult emergence was below 70% with at least 78% being females. Most female hybrids were fertile whereas most of the male hybrids were sterile when backcrossed to the G.p.palpalis parental line. All F1 males were capable of transferring a spermatophore but their mates rarely had sperm-impregnated spermathecae. Their testes rarely contained mature sperm; moreover, sperm, when present had low or no motility. During laboratory cage tests with virgin females of both subspecies and either sexually mature male G.p.palpalis or G.p.gambiensis, there was no indication for selective mating. The same was true when gamma irradiated males (120 Gy treatment in air) were used. In the latter case complete sterility was induced causing embryonic arrest in all inseminated female mates. Consequently, in ratio tests with untreated virgin G.p.palpalis females, untreated G.p.palpalis males and an increasing number of irradiated G.p.gambiensis males, there was a gradual decrease in production of viable offspring. The results of the present study are discussed with a view of using a combined hybridization and induced sterility in distinct geographical zones where the two subspecies are present. PMID- 2222008 TI - Bulinus africanus from Ituri (north-east Zaire) as a host for Schistosoma bovis. PMID- 2222009 TI - [Study of cellular immunity in patients with Mediterranean visceral leishmaniasis]. AB - Cellular immunity against Leishmania infantum antigens was studied in visceral leishmaniasis patients and healthy subjects living in a endemic area. Only the healthy subjects were TTL positive with production of gamma interferon, whereas the visceral leishmaniasis patients presented a transitory inhibition of their specific cellular response mechanisms. PMID- 2222010 TI - Impaired myocardial function and oxygen utilization due to protamine sulfate in an isolated rabbit heart preparation. AB - The myocardial effects of protamine, with and without heparin, were documented in this investigation. Isolated rabbit hearts (n = 30) were retrograde perfused with Krebs-Ringers bicarbonate solution aerated with 95% O2/5% CO2 through the aortic root (37 C, 80 mmHg). Developed left ventricular blood pressure, heart rate, coronary artery flow, contractility as reflected by peak +dp/dt, oxygen extraction (a-vO2), and oxygen consumption (VO2) were measured at baseline and continuously throughout the experiment. Protamine (25 micrograms, 50 micrograms, and 250 micrograms per mL of perfusate) was circulated in the Krebs-Ringers buffer to hearts perfused without heparin (groups I, II, and III) or hearts perfused with heparin added to the buffer solution, 0.1 IU/1.0 microgram protamine (groups IV, V, and VI). Blood pressure 4 minutes after protamine was less in groups III (-23 mmHg) and VI (-28 mmHg) than in groups I (-6 mmHg), II ( 18 mmHg), IV (-1 mmHg), and V (-7 mmHg). Heart rate changes (beats/minute) at 4 minutes revealed similar dose-dependent reductions (III and VI: -51, -55; II and V: -36, -36; and I and IV: -20, -16, respectively). Coronary artery flow at 4 minutes was slightly increased in groups III (9 mL/minute) and VI (15 mL/minute), but was relatively unchanged in the other groups. Decreases in contractility were apparent in all groups 4 minutes after protamine was started: group I, -14%; II, 16%; III, -30%; IV, -7%; V, -15%; and VI, -34%. Similarly declines in oxygen extraction and consumption were noted in all groups at the same time period and were greater in groups III (-53%, -44%) and VI (-55%, -49%) than in groups I ( 25%, -26%), II (-15%, -12%), IV (-48%, -49%) and V (-15%, -18%), with p less than or equal to 0.05 or p less than or equal to 0.01 compared to baseline. Three of ten hearts exposed to high-dose protamine stopped beating after 5 minutes. This investigation establishes, for the first time, that protamine has dose- and time specific adverse effects on cardiac contractility. In addition protamine decreases myocardial a-vO2 and VO2. These changes may contribute to certain adverse events accompanying the clinical administration of protamine. PMID- 2222011 TI - Long-term course of patients with persistent hypercalcitoninemia after apparent curative primary surgery for medullary thyroid carcinoma. AB - Thirty-one patients with persistent hypercalcitoninemia after seemingly adequate primary operation for medullary thyroid carcinoma (MTC) were followed for a mean period of 11.9 years after operation. Ten patients had sporadic MTC and the remaining patients were members of families with multiple endocrine neoplasia (MEN)--either MEN 2A (15 patients) or MEN 2B (six patients). Overall 5- and 10 year survival rates were 90% and 86%, respectively. Only four patients died at the completion of the study: two of MTC and two of unrelated causes. Eleven patients (35.5%) underwent surgical re-exploration after demonstration of recurrent disease clinically or radiologically. In no patient did the calcitonin level return to normal after re-exploration. The presence of more than three metastatic nodes at the time of initial operation was a statistically significant (p = 0.003) predictor for disease recurrence. Factors approaching statistical significance were patients younger than age 35 (p = 0.06) and the percentage of cells in the S phase of cell division (0.07). This data supports a conservative surgical philosophy in the management of the patient with persistent hypercalcitoninemia after resection of MTC. PMID- 2222012 TI - Selective evaluation and management of coronary artery disease in patients undergoing repair of abdominal aortic aneurysms. A 16-year experience. AB - Reduction of cardiac mortality associated with abdominal aortic aneurysm (AAA) repair remains an important goal. Five hundred consecutive urgent or elective operations for infrarenal nonruptured AAA were reviewed. Patients were divided into three groups based on preoperative cardiac status: group I (n = 260, 52%), no clinical or electrocardiographic (ECG) evidence of coronary artery disease (CAD); group II (n = 212, 42.2%), clinical or ECG evidence of CAD considered stable after further evaluation with studies such as dipyridamole-thallium scanning, echocardiography, or coronary arteriography; group III (n = 28, 5.6%), clinical or ECG evidence of CAD considered unstable after further evaluation. Group I had no further cardiac evaluation and groups I and II underwent AAA repair without invasive treatment of CAD. Group III underwent repair of cardiac disease before (n = 21) or coincident with (n = 7) AAA repair. In all instances, perioperative fluid volume management was based on left ventricular performance curves constructed before operation. The 30-day operative mortality rate for AAA repair in all 500 patients was 1.6% (n = 8). There was one (0.4%) cardiac-related operative death in group I, which was significantly less than the five (2.4%) in group II (p less than 0.02). Total mortality for the two groups were also significantly different, with one group I death (0.4%) and seven group II deaths (3.3%), (p less than 0.02). These data support the conclusions that (1) the leading cause of perioperative mortality in AAA repair is myocardial infarction, (2) correction of severe or unstable CAD before or coincident with AAA repair is effective in preventing operative mortality, (3) patients with known CAD should be investigated more thoroughly to identify those likely to develop perioperative myocardial ischemia so that their CAD can be corrected before AAA repair, and (4) patients with no clinical or ECG evidence of CAD rarely die of perioperative myocardial infarction, and thus selective evaluation of CAD based on clinical grounds in AAA patients is justified. PMID- 2222013 TI - Experience with cardiopulmonary bypass and deep hypothermic circulatory arrest in the management of retroperitoneal tumors with large vena caval thrombi. AB - From June 1984 to September 1989, 43 patients with large vena caval tumor thrombi from retroperitoneal malignancies underwent surgical treatment with cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). The primary malignancies were renal cell carcinoma (RCC) (n = 39), renal pelvic transitional cell carcinoma (n = 1), adrenal pheochromocytoma (n = 1), and renal (n = 1) or retroperitoneal (n = 1) sarcoma. The level of the caval thrombus was either suprahepatic (n = 27), intrahepatic (n = 14), or subhepatic (n = 2). In all cases the primary tumor and caval thrombus were completely removed. Concomitant procedures included coronary artery bypass grafting (n = 5), pulmonary resection (n = 2), and hepatic lobectomy (n = 1). The time of circulatory arrest ranged from 10 to 44 minutes (mean, 23.5 minutes). There were two operative deaths (4.7%), neither of them due to to the use of DHCA. Major postoperative complications occurred in 13 patients (30.2%). There were no ischemic or neurologic complications and no cases of perioperative tumor embolization. The median postoperative hospital stay was 9 days. Twenty-two patients (51%) are alive and enjoying a good quality of life. The 3-year patient survival rates in patients with localized (n = 24) versus metastatic (n = 15) RCC are 63.9% and 10.9%, respectively (p = 0.02). We conclude that CPB with DHCA facilities excision of retroperitoneal malignancies with large caval thrombi and provides the potential for cure with low morbidity and mortality rates. PMID- 2222014 TI - Urinary tract re-functionalization after long-term diversion. A 20-year experience with 177 patients. AB - From 1969 to 1990, previously diverted urinary tracts were 'undiverted' in 177 patients whose ages ranged from 1 to 31 years. Fifty-six of the patients (32%) had been diverted for 10 years or longer. There were 67 female and 110 male patients. Forty-four patients had only one kidney and in two of those patients it was a previous renal transplant. One patient was anephric at the time of reconstruction, having had two unsuccessful transplants. Most of the diversions had been considered permanent. Types of diversions that were reversed include ileal loop, colon conduit, loop ureterostomy or pyelostomy, end ureterostomy, cystostomy or vesicostomy, long-term nephrostomy, and ureterosigmoidostomy. PMID- 2222016 TI - Tumor necrosis factor-alpha mediates acid aspiration-induced systemic organ injury. AB - Acid aspiration-induced systemic organ injury is mediated by the sequestration of activated neutrophils (PMN). In other settings cytokines have been shown to increase neutrophil-endothelial adhesion, a requisite for injury. This study tests whether the systemic leukosequestration and permeability following localized aspiration is mediated by tumor necrosis factor (TNF)-alpha-induced synthesis of an adhesion protein. Anesthetized rats underwent tracheostomy and insertion of a fine-bore cannula into the anterior segment of the left lung. This was followed by the instillation of either 0.1 mL 0.1 N HCI (n = 18) or 0.1 mL saline in control rats (n = 18). Localized aspiration induced generalized pulmonary leukosequestration with 95 PMN/10 high-power fields (HPF) in the aspirated lung and 46 PMN/10 HPF in the nonaspirated lung, higher than control values of 7 PMN/10 HPF and 5 PMN/10 HPF in saline- and nonsaline-aspirated sides, respectively (p less than 0.05). The leukosequestration was associated with permeability edema shown by increased protein concentrations in bronchoalveolar lavage (BAL) of 3900 micrograms/mL in the aspirated and 2680 micrograms/mL in the nonaspirated side, higher than saline with 482 micrograms/mL and 411 micrograms/mL, respectively (p less than 0.05). There was generalized pulmonary edema following aspiration measured by increase in wet-to-dry weight ratios (w/d) of 6.6 in the aspirated and 5.1 in the nonaspirated lung, higher than control values of 3.5 and 3.4, respectively (p less than 0.05). Localized aspiration led to systemic leukosequestration documented by increases in myeloperoxidase activity (units/g tissue) of 2.2 and 1.7 in heart and kidney, higher than control values of 0.3 and 0.4, respectively (p less than 0.05). This event was associated with edema of these organs with w/d ratios of 4.6 and 4.3, relative to control values of 3.0 and 3.4 (p less than 0.05). Treatment of animals (n = 18) 20 minutes after aspiration with anti-TNF-alpha antiserum (rabbit anti-murine) but not normal rabbit serum (n = 18) reduced lung leukosequestration in the aspirated and nonaspirated segments (61 and 32 PMN/10HPF), BAL protein concentration (1490 and 840 micrograms/mL), and w/d ratio (4.3 and 3.7) (all p less than 0.05). In the heart and kidney there were reductions in myeloperoxidase activity (0.7 and 0.6) and w/d ratio (3.5 and 3.6) (both p less than 0.05). Treatment of rabbits (n = 18) with the protein synthesis inhibitor cycloheximide, 0.2 mg/kg/hr was as effective as TNF-alpha antiserum in modifying aspiration injury.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2222015 TI - The process of microbial translocation. AB - The process of microbial translocation was studied using Candida albicans, Escherichia coli, or endotoxin instilled into Thiry-Vella loops of thermally injured guinea pigs and rats. Translocation of C. albicans occurred by direct penetration of enterocytes by a unique process different from classical phagocytosis. Translocation between enterocytes was not observed. Internalization was associated with a disturbance of the plasma membrane and brush border, but most internalized organisms were not surrounded by a plasma membrane. Passage of the candida into the lamina propria appeared to be associated with disruption of the basal membrane with extrusion of cytoplasm of the cell and candida. Organisms in the lamina propria were commonly phagocytized by macrophages but also were found free in lymphatics and blood vessels. Translocation of E. coli and endotoxin also occurred directly through enterocytes rather than between them, but translocated endotoxin diffused through the lamina propria and muscular wall of the bowel wall by passing between rather than through the myocytes. These descriptive phenomena provide new insight into the role of the enterocyte and intestinal immune cells in the translocation process. PMID- 2222017 TI - Upper GI bleeding in an urban hospital. Etiology, recurrence, and prognosis. AB - Acute upper gastrointestinal bleeding (UGIB) continues to be a common cause of hospital admission and morbidity and mortality. This study reviews 469 patients admitted to a surgical service of an urban hospital. There were 562 total admissions because 53 patients were readmitted 93 times (recurrence rate, 20%). The most common causes of bleeding, all endoscopically diagnosed, included acute gastric mucosal lesion (AGML) (135 patients, 24%), esophageal varices (EV) (121 patients, 22%), gastric ulcer (108 patients, 19%), duodenal ulcer (78 patients, 14%), Mallory-Weiss tear (61 patients, 11%), and esophagitis (15 patients, 3%). Nonoperative therapy was sufficient in 504 cases (89.5%). Endoscopic treatment was used in 144 cases. Operations were performed in 58 cases (10.5%), including 29% of ulcers. Emergency operations to control hemorrhage were required in only 2.5% of all cases. The rate of major surgical complications was 11% and the mortality rate was 5.2%. There were 58 deaths (12.6%), with 36 deaths directly attributable to UGIB. Factors correlating with death include shock at admission (systolic blood pressure less than 80), transfusion requirement of more than five units, and presence of EV (all p less than 0.001). Most cases of UGIB can be treated without operation, including endoscopic treatment, when diagnostic endoscopy establishes the source. Subsequent operation in selected patients can be done with low morbidity and mortality rates. PMID- 2222019 TI - Ionized calcium, parathormone, and mortality in critically ill surgical patients. AB - A prospective study measured ionized calcium and parathormone sequentially at 48- to 72-hour intervals in 25 surgical intensive care unit patients. Twelve patients (48%) died at mean day 40 and median day 26. Levels of ionized calcium, parathormone, blood urea nitrogen, creatinine, albumin, magnesium, and phosphate for patients who lived were compared with levels for patients who died. The incidence of hypotension, renal failure (creatinine greater than or equal to 3.0), and bacteremia, as well as the amount of red cell, crystalloid, and colloid administration for the two groups was compared. Hypotension, bacteremia, red cells, crystalloid, and colloid were no different. On days 1 and 2 ionized calcium levels were significantly lower and parathormone levels significantly higher in nonsurviving patients; this difference persisted through days 3 and 4. Blood urea nitrogen and creatinine levels increased early in nonsurviving patients but renal failure, which occurred in nine nonsurviving patients, did not develop until mean day 14, median day 18. The phosphate level was slightly higher but still within normal range in nonsurviving patients. By days 5 and 6 ionized calcium and parathormone levels were no different in nonsurviving patients, despite there being no improvement in renal function. Magnesium and albumin levels were no different between groups. Ionized calcium levels are lower and parathormone levels higher early in nonsurviving patients. This difference is not readily explained by associated clinical conditions, including renal dysfunction. Although etiology remains unclear, low ionized calcium and elevated parathormone are early predictors of mortality in critically ill surgical patients. PMID- 2222018 TI - Surgical therapy in Barrett's esophagus. AB - Seventy-six patients with Barrett's esophagus were cared for during a 10-year period. Fifty-six patients (74%) presented with complications of the disease. There were 20 strictures, 7 giant ulcers, 11 cases of dysplasia, and 29 patients with carcinoma. In patients with benign disease, 93% had mechanically defective sphincters and 83% had peristaltic failure of the lower esophageal body. Esophageal pH monitoring showed excessive esophageal exposure to pH less than 4 in 93% and excessive exposure to pH more than 7 in 34% of the patients tested. Ninety-three per cent of patients with excessive alkaline exposure had complications, compared to only 44% with normal alkaline exposure (p less than 0.01). Gastric pH monitoring, serum gastrin levels, and gastric acid analysis supported a duodenal source for the alkaline exposure. Antireflux surgery was performed using Nissen fundoplication in 30, Belsey partial fundoplication in 3, and Collis-Belsey gastroplasty in 2. Six required resection with colon interposition. Good symptomatic control was achieved in 77% after antireflux surgery. Four patients had symptoms and signs of duodenogastric reflux; three required a bile diversion procedure. Fifteen patients had an en bloc curative resection with colon interposition. One patient with high-grade dysplasia on biopsy was found to have intramucosal carcinoma after simple esophagectomy. Five tumors were intramucosal, seven were intramural, and four were transmural. Lymph node involvement occurred only in the latter two. Actuarial survival 5 years after curative resection was 53%. Median survival time for patients after palliative resection or no resection was 12 months. Study of en bloc specimens indicated that extent of resection should be adapted to extent of disease: esophagectomy for intramucosal disease, en bloc esophagectomy with splenic preservation for intramural and transmural disease. Serum CEA was useful in detecting recurrent disease after surgery when the primary tumor stained positively for CEA. PMID- 2222020 TI - Surgical aspects of sclerosing cholangitis. Results in 178 patients. AB - Of 178 patients with sclerosing cholangitis treated since 1950, 88 patients had associated inflammatory bowel disease, 72 had no such history, and 18 had iatrogenic injury or stone disease. A total of 233 biliary operations were performed, with a 75% rate of temporary improvement after initial operation. Subsequent operations resulted in a lower success rate and a higher mortality rate. Radiologic findings included predominant extrahepatic, intrahepatic, and diffuse disease in 29%, 28%, and 43% of patients, respectively; no survival differences were noted. Seventy-five of one hundred three deaths (73%) were related to liver failure, bleeding, or sepsis. Of 14 patients undergoing portosystemic shunt, 13 died of surgical complications or related disease. Orthotopic liver transplantation was performed in 16 patients and resulted in eight deaths, mainly in patients who had previously undergone extensive surgical treatment. No survival differences were seen between the patients with inflammatory bowel disease, those without the condition, or those who had colectomy. Surgical treatment in patients with sclerosing cholangitis should be minimized. Orthotopic liver transplantation should be offered as the treatment of choice for patients with portal hypertension, refractory cholangitis, advanced cirrhosis, or progressive liver failure. PMID- 2222021 TI - Depressive effect of a Taenia solium cysticercus factor on cultured human lymphocytes stimulated with phytohaemagglutinin. AB - Cysticercosis caused by Taenia solium is associated with immunodepression of T and B lymphocytes. In order to ascertain if this parasite affects lymphocyte activity, a factor isolated from the parasite was tested on (3H) thymidine uptake by cultured human lymphocytes stimulated by phytohaemagglutinin. This dialysable factor had a molecular weight of less than 3500 Da, and was isolated from an extract of Cysticercus cellulosae. It decreased phytohaemagglutinin-stimulated uptake of (3H) thymidine. After the material was treated with RNase 'A', the suppressive activity was destroyed. It thus appears that the factor could correspond to an RNA fraction. PMID- 2222022 TI - Seroepidemiological studies on human pulmonary dirofilariasis in Spain. AB - Preliminary data are presented on a serological survey of the human population of an area with a high prevalence of Dirofilaria immitis infection in dogs. Five per cent of the sera were positive for IgG. Simultaneous radiological study revealed a pulmonary nodule in one of the positive patients, and in this case the evolution of IgG and IgM levels was followed over a period of three months. None of the positive sera reacted with Toxocara canis antigens. PMID- 2222023 TI - Malaria in refugee camps in eastern Sudan: a sero-epidemiological approach. AB - A study of the endemicity of malaria was carried out in two refugee camps in Sudan, and the advantages and disadvantages of treating either all febrile cases or only confirmed cases of malaria were considered. Based on the information obtained during the survey, guidelines for the treatment of malaria in such refugee camps are proposed. PMID- 2222024 TI - In vivo efficacy of quinine treatment for Plasmodium falciparum malaria in Malawian children. AB - Twenty-five Malwaian children with Plasmodium falciparum infection were studied for response to quinine in an eight-hourly dosage of 10 mg salt kg-1 body weight. The mean parasite clearance time, defined as the time after initiation of treatment when the first of two consecutive 12-hourly smears was negative for P. falciparum parasites, was 67 hours. The mean fever clearance time, defined as the time after initiation of treatment when the axillary temperature first fell below 37.5 degrees C and remained below this level for 48 hours, was 36 hours. Twenty four hours after the first dose of quinine, the geometric mean parasite density among the children studied had decreased by 84%, from 41 357-6586 parasites mm-3, and all children cleared their parasitaemia within 108 hours. Results of this study confirm that quinine remains effective in rapidly controlling P. falciparum parasitaemias in Malawi, where resistance to the 4-aminoquinolines is highly prevalent. PMID- 2222026 TI - A programme to reduce the risk of infection by Echinococcus multilocularis: the use of praziquantel to control the cestode in a village in the hyperendemic region of Alaska. AB - This paper reports the results of a 10-year field trial designed to reduce the risk of infection by Echinococcus multilocularis to residents of a village in a hyperendemic area (Savoonga, St. Lawrence Island). The objective was to prevent dispersal of infective eggs of the cestode within the village by means of monthly treatments of dogs with praziquantel. Northern voles, Microtus oeconomus, present in the village as commensals, served as an index of risk, as the incidence of infection in the voles provides information about the availability of eggs within the confines of the inhabited area. Voles were examined annually during early June before the population of overwintering voles was diluted by the first annual litters. The pretreatment infection-rate within the village was 29% (range 22 35%), and in control areas at some distance from the village for the entire study period it averaged 53% (284 infected voles from a sample of 533). Some fluctuation in incidence of infection in village voles occurred, apparently depending on the extent to which the residents kept their dogs chained and thus available for treatment. The success of the programme was demonstrated by the reduction in prevalence of infection to about 1% of voles in 1985, and an average infection rate during the last five years of the study of 5% (29 infected voles in a sample of 582). This 83% average reduction in the prevalence of the larval cestode within the village reflects a corresponding reduction in the risk of acquiring by the residents of the village. The method would be applicable for the control of E. multilocularis in most hyperendemic regions. Success depends, however, on elimination of unrestrained dogs and a precise schedule of treatment. PMID- 2222025 TI - Treatment of chloroquine-resistant malaria with esters of cephalotaxine: homoharringtonine. AB - The esters of cephalotaxine-harringtonine, homoharringtonine and deoxyharringtonine--have been reported by both Chinese and American oncologists as useful in the treatment of human nonlymphoblastic leukaemias and selected solid tumours of the head and neck. We report our results with homoharringtonine, currently a Phase II clinical trial drug with the National Cancer Institute, in the treatment of malaria. Homoharringtonine, 2.7-3.4 nM, was effective in causing 50% growth inhibition of two strains of chloroquine-resistant Plasmodium falciparum malaria in vitro. In vivo tests in mice infected with P. yoelii showed that this drug was effective in inhibiting parasite growth in this system as well. Histologically, the drug was associated with karyorrhexis. Drug-exposed cells showed decreased levels of putrescine and spermidine and increased spermine levels. Our findings not only demonstrate the potential usefulness of homoharringtonine in the treatment of chloroquine-resistant malaria, but also demonstrate the advantage of applying comparative biochemistry and an understanding of biological mechanisms in a rational approach to the development and treatment of diseases including malaria. PMID- 2222027 TI - Epidemiology of Mansonella perstans filariasis in the forest region of south Congo. AB - A study of Mansonella perstans filariasis conducted in the Chaillu mountains, Southern Congo, showed that 108 of 134 Pygmies (80.6%) and 79 of 302 Bantus (26.2%) presented with microfilaraemia. The mean microfilarial densities were also significantly higher in the Pygmies (1213 ml-1 of blood) than in the Bantus (136 ml-1). Ninety eight per cent of the Culicoides taken which had bitten man in the daytime were C. grahamii, and 0.8% of these were infected with filarial larvae. Two other species of Culicoides (C. kumbaensis and C. rutshuruensis) might also play a role in the transmission of M. perstans. PMID- 2222029 TI - Distribution of metacercariae in freshwater crabs in relation to Paragonimus infection of children in Liberia, West Africa. AB - An explanation was sought for the high prevalence of paragonimiasis in children in Liberia by examining possible modes of human infection from freshwater crabs. The occurrence, frequency of infection, and distribution of metacercariae of Paragonimus uterobilateralis in the freshwater crab Liberonautes latidactylus were studied. The muscles of the cephalothorax and of the legs were found to be the most frequently and most heavily infected parts of the crab. A likely risk of infection of children was considered to be the habit of chewing on, or ingesting in a raw state, the walking legs of infected crabs. Possible contamination of the hands of cooks with metacercariae from the internal organs or haemolymph of infected crabs was thought to be a minor route of infection. PMID- 2222028 TI - Leptospiral infection: a household serosurvey in urban and rural communities in Barbados and Trinidad. AB - A longitudinal study of leptospiral agglutinins in subjects five years of age and over was undertaken in Trinidad and Barbados between 1980 and 1982. Households were sampled randomly from one urban and two rural communities on each island, giving a total of 576 eligible individuals in Barbados and 524 in Trinidad. Participants were examined three times at approximately annual intervals. The prevalence of seropositivity at a titre of 1:50 using the microscopic agglutination test was 18.5% in Barbados and 21.9% in Trinidad. Prevalence increased steeply with age in both sexes and was higher in males than females on both islands. There was a marked difference in predominating serogroups on the two islands--Autumnalis (42% of positive cases) predominated in Barbados while Bataviae (29% of positive cases) predominated in Trinidad. Estimates of incidence rates for seroconversion were 2.9% per annum for Barbados and 3.5% per annum for Trinidad. Occupational risk varied between the islands, but in both cases highest seropositivity rates (greater than 50%) were found in outdoor labourers and lowest were found in indoor non-manual workers and urban homeworkers. In Barbados seroprevalence was higher among persons who cleared drains or who had contact with livestock. Lack of an inside toilet was associated with an increase in seropositivity on both islands. There was little evidence of household clustering of seropositive cases. PMID- 2222030 TI - Amoebic liver abscess: the effect of aspiration on the resolution or healing time. AB - Recent sonographic monitoring of patients treated for amoebic liver abscess has shown the healing or resolution time varying between 10 and 300 days. The effect of percutaneous needle aspiration under or resolution time was studied in 36 patients. Nineteen patients had drugs and needle aspiration under ultrasound guide whilst the 17 patients had drugs--metronidazole, diloxanide, and chloroquine--alone. Both groups were monitored clinically and sonographically. Results showed that the abscess cavities of 18 out of 19 patients (94.7%) of the aspirated group and 10 of 17 patients (58.8%) of the non-aspirated group had resolved at the end of three weeks. The difference in response to treatment was significant (P less than 0.02) more so for lesion size more than 6 cm (P less than 0.01). There was also a more rapid clinical response in the aspirated group than in the non-aspirated group, particularly for patients whose lesion size was more than 6 cm (P less than 0.01). In conclusion, percutaneous needle aspiration is safe, enhances clinical recovery, and accelerates resolution particularly in patients with large abscess cavities. PMID- 2222032 TI - Survival rates of Bulinus globosus during aestivation. PMID- 2222033 TI - How many species are in the Anopheles punctulatus group? PMID- 2222031 TI - Hydatidosis among Iraqi children. AB - Thirty girls and 28 boys (aged from 3.6-18 years old) with hydatid disease were treated surgically. Data were statistically analysed according to age, sex and organs affected. The greater number of cases was in the age group 10-14 years. Liver involvement was more frequent (72.2%) than lung involvement (27.8%). Clinical manifestations of hepatic hydatidosis included fever, hepatomegaly and abdominal pain, while those of pulmonary hydatidosis included cough, haemoptysis and fever. The Casoni, indirect haemagglutination and ultrasound tests were positive in 55, 76 and 100% of cases respectively. PMID- 2222034 TI - Using ICD-9-CM and CPT in the nineties. PMID- 2222035 TI - Assessing the prognosis of thymomas. PMID- 2222036 TI - Traumatic bronchial rupture and other major thoracic injuries. PMID- 2222037 TI - Relief of tracheal compression by aortopexy. AB - We have performed aortopexy in 12 children with tracheal compression. Six infants had compression secondary to a vascular anomaly (group 1), and the other 6 had previous repair of esophageal atresia (group 2). Eleven of the 12 children are alive after a mean follow-up of 36 months. In group 1, 1 patient died and 3 patients (50%) experienced recurrent respiratory distress. Five infants sustained a major postoperative complication, and the average postoperative hospital stay was 25 days. In group 2, however, aortopexy was uniformly successful. There were no deaths, no postoperative complications, and no cases of postoperative respiratory distress, and the mean postoperative hospital stay was only 10 days. For children with reflex apnea after repair of esophageal atresia, aortopexy is lifesaving and can be performed with minimal morbidity and mortality. Great caution is indicated in children with tracheal compression from other causes. PMID- 2222038 TI - Selective monitoring of patients with suspected blunt cardiac injury. AB - Blunt chest trauma can result in cardiac injury with consequent dysrhythmias, valve malfunction, or frank rupture. Typically, patients with blunt chest trauma and suspected cardiac injury have required cardiac monitoring for 48 to 72 hours. Predicting which patients with blunt chest trauma are not at risk for cardiac complications would obviate many patient-hours of monitoring in the intensive care unit. This series examines the sensitivity of two-dimensional surface echocardiography in predicting cardiac complications. Over a 24-month period, 115 patients were admitted with blunt chest trauma and prospectively evaluated for cardiac injury with admission electrocardiograms, serial creatine kinase isoenzyme studies, and two-dimensional echocardiography. Thirty-one patients (27%) had abnormal two-dimensional echocardiograms. In 8 (25.8%) of these patients, cardiac complications requiring treatment developed. Eighty-four patients (73%) had normal two-dimensional echocardiograms, and a cardiac complication requiring treatment developed in only 1 (1.2%) of them. Of the 9 patients who required treatment of cardiac complications, 3 had normal admission electrocardiograms and only 1 had elevated levels of the myocardial-specific isoenzymes of creatine kinase. We believe two-dimensional echocardiography is a sensitive test for evaluating cardiac injury resulting from blunt chest trauma and is helpful in selecting those patients who require monitoring in the intensive care unit. PMID- 2222039 TI - Analysis of prognostic factors and clinicopathological staging of thymoma. AB - The prognostic value of four clinical variables (age and sex of patients, association with myasthenia gravis, and clinical stage) and histological type was analyzed in 83 consecutive patients with thymoma, histologically classified as cortical, medullary, and mixed. Age, sex, and association with myasthenia gravis did not prove to represent significant prognostic factors; clinical stage and histological type, on the contrary, had a highly significant prognostic value (p less than 0.001). A model of clinicopathological staging, based on both clinical stage and histological type, in which three major prognostic groups are considered is proposed. The degree of significance of this model is higher (p less than 0.0001) than that of clinical stage and histological type considered individually; its validity is further supported by the results of multivariate analysis according to the Cox regression model (p = 0.0001). We think it represents a prognostically valuable approach to the problem of management of thymoma. PMID- 2222040 TI - Intraoperative ultrasonic imaging of the ascending aorta in ischemic heart disease. AB - In an attempt to locate any atherosclerotic lesion in the ascending aorta and to prevent embolization, intraoperative B-mode ultrasonography was performed in 100 patients with ischemic heart disease (31 women and 69 men). Ultrasonography was carried out with a 10-MHz probe placed directly on the ascending aorta. Ultrasonic imaging demonstrated an atherosclerotic lesion in the lower half of the aorta in 76 patients (76%), a lesion in the upper half of the aorta in 89 patients (89%), and a lesion at the orifice of the innominate artery in 99 patients (99%). Prospective palpation identified an atherosclerotic lesion in 12 (25%) of 48 patients. Thoracic computed tomography in 79 patients showed calcification in the lower half of the aorta in 6 patients (7.6%) and in the upper half of the aorta in 11 (13.9%). Palpation and thoracic computed tomography underestimated the frequency of atherosclerotic lesions. Intraoperative ultrasonography accurately identified atherosclerotic disease. This technique allows the surgeon to modify cannulation, aortic clamping, and operative technique to reduce the risk of perioperative stroke due to embolization of atherosclerotic debris from the ascending aorta. PMID- 2222041 TI - Prevention of paraplegia during aortic operations. AB - Ischemic spinal cord injury after aortic cross-clamping may be produced by a steal phenomenon. The present study investigates this possibility 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 1) and after occlusion of the abdominal aorta at L-1 (group 2). Exclusion of the thoracic aorta by a second clamp at T-13 restored oxygen tension almost to the original level, whereas segmentation of the abdominal aorta up to S-1 hardly affected oxygen tension in the area of the artery of Adamkiewicz in most of the animals. We conclude that after aortic cross-clamping, blood tends to drain away from the spinal cord rather than supplying it longitudinally. Without knowledge of the position of the Adamkiewicz artery in humans as well as of the competence of the collateral circulation in the excluded segment, it is necessary to develop a new strategy for repair of the aorta. We describe and discuss two surgical techniques for the prevention of paraplegia after aortic cross-clamping: the counterocclusion technique and the bypass fractionated technique. PMID- 2222042 TI - Combined internal mammary artery graft for coronary artery revascularization. AB - Five patients with multiple-vessel coronary artery disease underwent isolated coronary artery bypass grafting with a technique involving both internal mammary arteries and a small piece of interposed saphenous vein. The combined internal mammary artery grafts were used for sequential grafting. A total of 20 anastomoses were performed (average number, 4 anastomoses per patient). There were no operative deaths. Postoperative complications included reoperation for bleeding in 1 patient and diaphragmatic dysfunction in another. Postoperative coronary angiography 2 days before discharge (mean time, 10 days postoperatively) revealed that all the sequential anastomoses with the combined IMA graft were patent. Exercise tolerance tests performed 3 and 11 months postoperatively indicated excellent results and no ischemia. Based on this experience, we conclude that this method appears promising for multivessel coronary artery bypass grafting. PMID- 2222043 TI - Surgical treatment of cardiac myxomas: long-term results. AB - Between 1965 and 1988, 22 patients underwent 24 operations for cardiac myxomas. Two patients had the complex myxoma syndrome. Mitral valve replacement was required at initial operation in 2 patients. One patient died perioperatively, and 5 others died subsequently. The 16 surviving patients recently underwent evaluation at a mean duration of 9 years after operation. Ten are asymptomatic and 6 have New York Heart Association class II symptoms. Nine patients continue to be employed. Eleven are in sinus rhythm, 3 have permanent pacemakers, and 2 have chronic atrial arrhythmias. Echocardiography showed atrioventricular valve insufficiency in 3 patients and reduced contractility in 4, but no new tumor recurrences. The long-term prognosis of this relatively large group of patients with cardiac myxomas has been good. Patients without the complex myxoma syndrome had no recurrence, whereas 2 patients did require reoperation for mitral valve replacement. Long-term disability and chronic arrhythmias have been infrequent, and functional status and employability of these patients have been very good. PMID- 2222044 TI - Cor triatriatum: clinical presentation and surgical results in 12 patients. AB - Twelve patients with cor triatriatum have been seen at our institution since 1979. The clinical presentation, diagnostic evaluation, and surgical results are outlined in this retrospective review. Operation is the treatment of choice for this rare congenital cardiac defect. One patient died 1 day before scheduled operation, and 2 patients died postoperatively, yielding a surgical mortality rate of 17% and an overall mortality rate of 25%. Resection of the obstructing atrial membrane was performed using hypothermic cardiopulmonary bypass in all cases. Left atriotomy was performed in 6 patients, and right atriotomy was performed in 7. The two postoperative deaths occurred in patients who had serious associated cardiac defects. Associated anomalies include atrial septal defect, persistent left superior vena cava, and partial anomalous pulmonary venous return. The postoperative course has been excellent in all 9 surviving patients; all remain asymptomatic. Cor triatriatum is amenable to surgical repair with excellent results when diagnosed early and when not complicated by other severe cardiac anomalies. PMID- 2222045 TI - Tracheal and main bronchial disruptions after blunt chest trauma: presentation and management. AB - Tracheobronchial disruption is one of the less common injuries associated with blunt thoracic trauma. This injury can be life threatening, however, and failure to diagnose it early can lead to disastrous acute or delayed complications. Nine cases of tracheobronchial disruption in the setting of nonpenetrating thoracic trauma were seen at four Los Angeles trauma centers between 1980 and 1987. Mechanism of injury, presentation, diagnosis, and management of these patients were reviewed. Disruptions involved the trachea in 3 patients, the right bronchus in 5 patients, and the left bronchus in 2 patients. Tracheobronchial disruptions occurred in settings of high-energy impact-type injuries and were more likely to have associated injuries than they were to occur alone. Common presenting signs included subcutaneous emphysema, dyspnea, sternal tenderness, and hemoptysis. Radiographic findings were most commonly pneumothorax, pneumomediastinum, and clavicle or rib fractures. Rigid bronchoscopy and fiberoptic bronchoscopy were both highly accurate methods for diagnosis but only in the hands of trained cardiothoracic surgeons. Delay in diagnosis increased the likelihood of postoperative complications. PMID- 2222046 TI - Subaortic obstruction: intraoperative echocardiography as an adjunct to operation. AB - Fourteen patients undergoing operation for subaortic obstruction (membranous obstruction in 11 patients, tunnel obstruction in 2 patients, obstruction due to reduplicated mitral valve tissue in 1 patient) were evaluated by intraoperative epicardial echocardiography. In all 9 patients with "discrete" obstruction who underwent prebypass epicardial echocardiography, the septal and lateral attachments of the lesion were correctly demonstrated. The precise extent of tunnel stenosis was seen in both patients. The lateral attachment of the membrane in 4 patients and multiple extensions in another 2 were identified by the epicardial study (having been missed on precordial echocardiography). The discrete membrane was enucleated in 10 of the 11 patients and was partially resected in 1. One tunnel obstruction was completely relieved; the other was partially relieved. Reduplicated mitral valve tissue in the remaining patient was completely resected. Epicardial imaging after bypass showed remnants of the membrane in 2 patients. Intraoperative Doppler echocardiography and color flow imaging confirmed the absence of clinically significant residual gradients (less than 20 mm Hg) in all but 1 patient with tunnel obstruction. Epicardial imaging provided excellent morphological information about obstructive lesions of the left ventricular outflow tract and enabled immediate assessment of surgical repair. PMID- 2222047 TI - Diagnostic imaging and surgical treatment of dumbbell tumors of the mediastinum. AB - We describe the diagnostic procedures and surgical approaches employed in 5 patients with dumbbell tumors of the mediastinum. Magnetic resonance imaging accurately described the existence and longitudinal extension of the intraspinal component of the tumor and assisted in choosing the appropriate surgical approach. Both the intrathoracic and intraspinal components of the tumor were resected at one time by a thoracic and neurosurgical team. We employed the Grillo technique three times and a separate laminectomy and thoracotomy approach. Magnetic resonance imaging proved the most useful diagnostic technique for suspected dumbbell mediastinal tumors. In our experience, the extended thoracotomy proposed by Grillo and co-workers worked well for small tumors involving only one foramen in which the intraspinal extension was limited to 2 to 3 cm, and when no more than two laminectomies were required. On the other hand, thoracotomy and a longitudinal paravertebral incision are preferable for larger tumors (more than 4 cm) involving more than one foramen in which the intraspinal extension exceeds 2 to 3 cm, for tumors requiring multiple laminectomy, and when bony infiltration is present. PMID- 2222048 TI - Reoperations on heart valve prostheses: an analysis of operative risks and late results. AB - To evaluate risks and complications of reoperations on heart valve prostheses, we reviewed data on 183 patients who underwent reoperation because of prosthetic valve malfunction. The incremental effect of the redo procedure on hospital mortality and morbidity was studied by comparing primary and reoperative procedures and analyzing a series of possible predisposing factors. Late survival after first and second reoperations was computed, and possible determinants of late mortality were examined. Overall operative mortality was 8.7%; emergency operation (p = 0.0001), previous thromboembolism (p = 0.05), and advanced New York Heart Association functional class (p = 0.031) were the independent determinants. In a series of 1,355 patients having primary or secondary isolated valve replacement, the redo procedure was a significant risk factor in the univariate analysis (p = 0.025) but not in the multivariate analysis except for the subset of patients having mitral valve replacement (p = 0.052). The postoperative course was quite complicated, as evidenced by the long mean stay in the intensive care unit (mean stay, 3.8 days; longer than 2 days for 26% of the survivors). Nevertheless, postoperative complications were not significantly greater after a redo procedure than after a primary operation. Actuarial survival at 7 years was 57.3% +/- 8%. A comparison with a nonhomogeneous series from our institution did not demonstrate significant differences. In the subset of 16 patients having a second reoperation, late survival was 37.8% +/- 16% at 2 years. Advanced New York Heart Association class (p = 0.0001), double prosthetic valve dysfunction (p = 0.003), and any indication other than primary tissue failure (p = 0.06) were determinants of late mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222049 TI - Complement activation and lung permeability during cardiopulmonary bypass. AB - Pulmonary dysfunction after cardiopulmonary bypass has been attributed to the damaging effects of complement activation on the lung. To further explore this phenomenon, we measured plasma levels of activated complement components (radioimmunoassay), assessed neutrophil n-formyl-methionyl-leucyl-phenylalanine (FMLP) receptor status (radioligand saturation binding assay), and quantified pulmonary epithelial permeability as radioaerosol lung clearance of technetium 99m-labeled diethylenetriamine pentaacetic acid in a series of 8 patients undergoing cardiopulmonary bypass. Significant elevations of plasma C3adesArg, C4adesArg, and C5adesArg levels were seen just after CPB, indicating activation of both the classic and alternate complement pathways. Neutrophil activation was evident as increased expression of neutrophil FMLP surface receptors after bypass. Despite the presence of complement and neutrophil activation, increased pulmonary epithelial permeability was not seen. These data support the hypothesis that complement and neutrophil activation during cardiopulmonary bypass is not associated with acute lung injury, at least not pulmonary epithelial injury. One can therefore infer that increased pulmonary epithelial permeability in patients at high risk for and experiencing sepsis-induced and trauma-induced adult respiratory distress syndrome may be due to factors other than complement and neutrophil activation. PMID- 2222050 TI - Complications after cardiac operations in patients with severe pulmonary impairment. AB - The postoperative courses of 39 patients with severe lung disease (31 with obstructive disease and 8 restrictive) who underwent a cardiac operation were retrospectively reviewed. The stay in the intensive care unit of the study group was 7.9 +/- 10.3 days (mean +/- standard deviation) compared with 2.4 +/- 3.9 days for the control group (100 patients with less impaired pulmonary function) (p less than 0.001). The study group also had a greater number of valve replacements than did the control group (p less than 0.01). Patients with obstructive disease had more respiratory complications than did patients with restrictive disease (p less than 0.05). There were 21 cases of atelectasis. Effusions were noted in 11 patients. Ten patients had bronchospasm. Bronchial secretions were a major problem in 6 patients. Pneumonia developed in 4 patients, and pneumothorax occurred in 3 others. The two in-hospital deaths were not directly related to pulmonary complications. Our findings indicate that (1) patients with severe lung impairment generally do well after a cardiac operation but have more postoperative pulmonary complications than patients with less impairment; (2) patients with restrictive pulmonary disease appear to fare better than those with obstructive disease; (3) pulmonary function tests can alert the clinician to the possible risk of postoperative complications, but they cannot, by themselves, be used to exclude patients from operation; and (4) patients with severe pulmonary impairment facing valve replacement are at greater risk of pulmonary complications than patients having other types of cardiac surgical intervention. PMID- 2222052 TI - Pharyngoesophageal perforation after blunt neck trauma. AB - Pharyngoesophageal perforation secondary to blunt neck trauma is an uncommon injury that can cause serious morbidity and mortality if not recognized and treated. Pharyngeal perforation secondary to blunt trauma sustained while boxing is reported. Review of the world literature found 10 cases of pharyngoesophageal perforation secondary to blunt neck trauma. Analysis of these cases indicates that perforations less than 2 cm and limited to the pharynx may be treated medically with close observation. Large perforations and those perforations that extend to the esophageal inlet or involve the esophagus exclusively are best treated surgically. PMID- 2222051 TI - Results in 104 patients undergoing bronchoplastic procedures for bronchial lesions. AB - Bronchoplastic procedures were used in 104 patients with various bronchial disorders. Ten had benign lesions and 94, malignant tumors. The principal operative procedures were sleeve lobectomy and sleeve pneumonectomy for bronchogenic carcinoma, but 11 limited bronchial resections were performed in patients with benign lesions, minute bronchogenic carcinomas, and low-grade malignant tumors. Of the 94 patients with malignant tumors, 79 underwent a bronchoplastic procedure without carinal resection (sleeve lobectomy in 75 and limited bronchial resection in 4), and there was one operative death (1.3%). The overall 5-year survival rate for the patients with bronchogenic carcinoma in this group was 45% and that for patients undergoing curative resection, 57% (survival of patients in stages I, II, and IIIA was 79%, 55%, and 30%, respectively). A bronchoplastic procedure with carinal resection was performed in 15 patients. Twelve in this group underwent sleeve pneumonectomy. There were two operative deaths, and 1 patient has survived for longer than 4 years. Two patients with low grade malignant tumors underwent carinal resection without lung resection and are still alive. We believe that bronchoplasty is a safe and valuable procedure and that limited bronchial resection appears to be the procedure of choice for localized bronchial lesions. PMID- 2222053 TI - Use of the variable-length intraluminal sutureless graft. AB - From August 1987 to May 1988 we treated 4 patients with acute ascending aortic dissections with a variable-length intraluminal aortic prosthesis. This operation uses profound hypothermic circulatory arrest and represents a refinement of existing techniques. There was no mortality, and morbidity was minimal. Modifications of this technique can be used in performing proximal aortic root reconstruction with a composite valved conduit. The use of a variable-length intraluminal prosthesis and hypothermic circulatory arrest is illustrated. This is a safe and useful technique in select cases of acute ascending aortic dissection. PMID- 2222054 TI - Intraoperative bronchial aspiration of ruptured pulmonary hydatid cysts. AB - Ruptured pulmonary hydatid cysts are seen clinically and radiologically as persistent cavitary lesions of the lung. Bronchi opening into the pericyst cavity allow for discharge of fluid matter but not the escape of solid remnants of the collapsed parasite. Operative manipulation of the involved lung in the course of surgical management of chronic ruptured pulmonary hydatids can force fragments of the laminated membrane or small daughter cysts into the bronchial tree. Such extruded solid fragments lodge in bronchi of the same or opposite lung with resulting acute obstruction of airways. Intraoperative bronchial aspiration of hydatid material was seen in 7 patients with ruptured hydatid cysts of the lung, either primary or secondary to transdiaphragmatic extension of liver hydatids. The first clinical sign can be unexplained difficulty in ventilation. Effective management consists of prompt exposure of the stem bronchus on the operative side, with bronchotomy for suction retrieval of escaped solid fragments of the parasite. PMID- 2222055 TI - Value of transesophageal echocardiography during repair of congenital heart defects. AB - Two-dimensional transesophageal color Doppler echocardiography was employed intraoperatively in 30 children undergoing repair of a variety of simple and complex cardiac malformations. There were 16 female and 14 male patients, with a mean age of 9 +/- 3 years (range, 4 to 13 years) and a mean weight of 31 +/- 9 kg (range, 16 to 50 kg), 16 children weighing less than 30 kg. A standard, commercially available transesophageal echocardiography probe (5 MHz, 64 elements) was used in all patients without complications. Transesophageal echocardiography proved helpful in selecting the surgical approach, in assessing the adequacy of surgical repair, in detecting residual intracardiac shunts, and in allowing uninterrupted monitoring of ventricular performance throughout the procedure. Our initial experience suggests that transesophageal echocardiography is a valuable tool to be used in children with congenital cardiac malformations, particularly in those requiring complex intracardiac procedures. The amount of information obtained by the surgeon should favor the routine use of transesophageal echocardiography during open heart procedures and stimulate the development of probes to be safely used even in infants and newborns. PMID- 2222056 TI - Swan-Ganz catheter-induced massive hemoptysis and pulmonary artery false aneurysm. AB - Swan-Ganz catheter-induced massive hemoptysis and later pulmonary artery false aneurysm occurred in a patient with prosthetic mitral regurgitation. This patient was successfully managed by double-lumen endotracheal intubation, control of pulmonary hypertension, reversal of anticoagulation, mitral valve re-replacement, and transcatheter embolization. The pertinent literature is reviewed. PMID- 2222057 TI - Coexisting thymic carcinoid tumor and thymoma. AB - Thymic carcinoid tumors are unusual neoplasms that are different from thymomas. We report a case of coexisting thymic carcinoid tumor and thymoma associated with myasthenia gravis. The clinicopathological findings are discussed with a review of the literature. PMID- 2222058 TI - Cystic medionecrosis of the coronary arteries and fatal coronary vasospasm. AB - The histopathological basis of coronary vasospasm is not well defined. We report a patient with directly observed coronary artery spasm in whom cystic medionecrosis of the coronary arteries and great vessels and myxomatous degeneration of the mitral valve were evident. We suggest that myxoid connective tissue lesions of the heart may be linked to coronary vasospasm. PMID- 2222059 TI - Left superior vena cava: a pitfall in computed tomographic diagnosis with surgical implications. AB - We report 2 cases in which computed tomography of the mediastinum demonstrated an abnormality originally misinterpreted as lymphadenopathy but subsequently shown to represent a left superior vena cava. Misinterpretation may result in errors in optimum treatment and may complicate surgical exploration of the mediastinum. These 2 cases are presented to remind radiologists and surgeons of the possibility of this unusual anatomy. PMID- 2222060 TI - Liver transplantation with atrioatrial anastomosis for Budd-Chiari syndrome. AB - We report the case of a young woman with Budd-Chiari syndrome in whom mesentericoval shunt was first performed, followed by transcaval liver resection and hepatoatrial anatomosis 3 years later. Liver transplantation became necessary 5 years later because of deterioarating liver function with portal hypertension and bleeding. Successful transplantation was performed with atrioatrial anastomosis with help of cardiopulmonary bypass, simplifying considerably the technical procedure and reducing dramatically blood loss. PMID- 2222061 TI - Resection of the superior vena cava for primary lung cancer: 5 years' survival. AB - We describe a patient with squamous cell carcinoma of the right lung that required a resection of the superior vena cava combined with a tracheal sleeve pneumonectomy. The superior vena cava was totally replaced with a polytetrafluoroethylene graft with 115 minutes cross-clamping of the superior vena cava. The patient remains healthy and the polytetrafluoroethylene graft remains patent 5 years 4 months after operation. PMID- 2222062 TI - Polytetrafluoroethylene graft for spontaneous coronary dissection: 7-year follow up. AB - Spontaneous coronary artery dissection remains an exceedingly rare cause of myocardial ischemia. The patients are usually young and female, and the dissection is frequently fatal. The use of polytetrafluoroethylene as an aortocoronary conduit is generally followed by early occlusion. We report a case of spontaneous right coronary dissection in which a polytetrafluoroethylene graft was placed that was observed to remain patent by angiography at least 72 months after operation. PMID- 2222063 TI - Modified pericardial closure to protect cardiovascular structures during sternal reentry. AB - A technique is described for covering the anterior surface of the heart and bypass grafts with autologous pericardium after myocardial revascularization. A trapezoidal flap is created that incorporates bilateral relaxing incisions to avoid distortion of grafts or increased risk of pericardial tamponade. PMID- 2222064 TI - Rapid placement of the Hemopump and hemofiltration cannula. AB - Hypervolemia, a potential complication in patients on ventricular assist device support, can be managed by use of continuous arteriovenous hemofiltration. The Hemopump, a new catheter-mounted, transaortic axial-flow ventricular assist device, and the vascular access catheter for the Diafilter-30 Hemofilter system, used in continuous arteriovenous hemofiltration, are both usually inserted by way of the femoral artery. Because placing two large catheters in the femoral artery of a patient with peripheral vascular disease can compromise circulation, a technique for placing them in the abdominal aorta was developed. Two patients have undergone combined Hemopump and hemofiltration treatment, and neither experienced complications. Such techniques may benefit more patients in the future, as the usefulness of the Hemopump is proved. PMID- 2222065 TI - Improved cannulation method for extracorporeal membrane oxygenation. AB - Extracorporeal membrane oxygenation has been shown to be useful for patients in reversible cardiogenic shock. Effective arterial cannulation techniques for infants have been developed that are simple to use and require minimal subsequent vascular repair or reconstruction after removal. Groin cannulation in adults frequently requires bidirectional arterial cannulation to ensure adequate distal perfusion as well as frequent complex arterial repairs after discontinuation. We describe a simple arterial cannulation technique using a single right-angle, high flow arterial cannula. With this technique adequate bidirectional arterial perfusion is maintained with a single arterial cannula while the need for vascular repairs or reconstruction is minimized. PMID- 2222066 TI - Origins of intraaortic balloon pumping. AB - In 1968, the Journal of the American Medical Association published a paper on the "Initial clinical experience with intraaortic balloon pumping in cardiogenic shock," which gave the results of the first clinical use of the procedure developed in our laboratory. For more than 2 years, our group was the only one using intraaortic balloon pumping clinically. Later, intraaortic balloon pumping was used by others, and despite poor clinical salvage, the hemodynamic benefit was demonstrated convincingly. At the present time, approximately 70,000 balloon pump procedures are performed annually. PMID- 2222067 TI - Guidelines for transfusion support in patients undergoing coronary artery bypass grafting. Transfusion Practices Committee of the American Association of Blood Banks. AB - We have reviewed the impact of evolving issues in coronary artery bypass grafting (CABG) on transfusion support for these patients. Issues include increased awareness of transfusion risks, reappraisal of traditional indicators triggering transfusion, and evolving alternatives to homologous blood transfusion such as autologous blood and pharmacologic therapy. These issues have been prompted by programs, such as the National Institutes of Health Consensus Conferences, to provide physicians with guidelines for appropriate use of blood components. However, evidence suggests that transfusion practice in coronary artery bypass grafting procedures remains variable and does not take into account the results of recently published clinical studies. We have therefore developed guidelines and recommendations for transfusion support in patients undergoing coronary artery bypass grafting. In summary, they are the following. 1. Institutions with coronary artery bypass grafting programs should establish a multidisciplinary approach to use a combination of interventions designed to minimize homologous blood exposure. 2. Prophylactic transfusion of plasma and platelets are of no benefit and therefore carry an unnecessary risk to the patient. 3. Special request products such as designated blood donation from first-degree relatives should not be used because of the risk of transfusion-associated graft versus host disease. 4. For support of intravascular volume, crystalloids or colloids should be used because they do not have the potential to transmit infection. PMID- 2222068 TI - Retrotracheal mediastinal goiter with contralateral extension. PMID- 2222069 TI - Postirradiation pericardiectomy. PMID- 2222070 TI - Efficacy of pulmonary artery versus left ventricular venting. PMID- 2222071 TI - Thymectomy for myasthenia gravis. PMID- 2222072 TI - Intraoperative photodynamic therapy for malignant mesothelioma. PMID- 2222073 TI - Respiratory function after thoracic operations. PMID- 2222074 TI - Seminal vesicles: development, secretory products, and fertility. AB - The development of the seminal vesicle from the mesonephric duct is described. Particular attention is given to the recent biochemistry of seminal vesicle proteins. Proteins in the seminal vesicle fluid are few in number, may be insoluble at certain pH, and frequently form large macromolecular aggregates. Although not an absolute requirement for fertility, seminal vesicle fluid assists in a number of ways to insure fertility. A biochemical model is presented that demonstrates that cAMP dependent phosphorylation may be an important interaction between sperm and certain seminal vesicle proteins. PMID- 2222075 TI - Immature spermatogenic cells and leucocytes in normal and abnormal semen. AB - The frequency and ranges of the immature germinal cells (IGC) were established in 286 semen analyses from normozoospermic (group I), oligozoospermic (group II), and azoospermic (group III) subjects. The mean total count of IGC was greater between men from group I than between participants from groups II and III. Scd spermatids were the cells most frequently observed and the spermatogonia the most unfrequently seen. Sab and Scd spermatids were the most common cells observed in group I, whereas Scd and primary spermatocytes were the most common in group II, and Scd and secondary spermatocytes were the most common in group III. Correlation was found between sperm concentration and the IGC total count. Significant differences were not found when epithelial cell and leucocyte concentrations were compared between groups. PMID- 2222077 TI - Effect of pineal indoles on testicular histology of mice. AB - The effect of late afternoon injections of melatonin, 5-methoxytryptamine, 5 methoxytryptophol, and 5-methoxyindole-3-acetic acid on testicular histology in mice were examined. Melatonin and 5-methoxytryptophol injections caused a reduction in the diameters of seminiferous tubules. The tests of melatonin treated animals underwent some detectable regressive changes in the seminiferous tubules, whereas administration of 5-methoxytryptamine or 5-methoxytryptophol appeared to cause atrophy in some tubules. The percentage of aspermic tubules in melatonin-treated and methoxytryptamine-treated mice was significantly higher than that of the control. In involuted testes, some seminiferous tubules contained only Sertoli cells together with spermatogonia and spermatocytes, but no discernible spermatids and spermatozoa. Regressing spermatids and cell debris were frequently observed in the tubules. The tested of mice that received daily injections of 5-hydroxytryptophol and 5-methoxyindole-3-acetic acid were indistinguishable from those of the controls. PMID- 2222076 TI - Antisticking protein factors in buffalo blood serum. AB - Buffalo blood serum is a potent source of antisticking factor (ASF) that inhibits with high affinity adhesion of goat epididymal spermatozoa to the glass surface of hemocytometer counting chamber. The serum is also capable of inhibiting glass sticking of spermatozoa of the buffalo, ram, and bull. The serum ASF activity is nondialyzable and stable to heat treatment at 100 degrees C for two minutes. The activity of the serum ASF was lost completely when treated with trypsin (50 micrograms/ml) at 37 degrees C for thirty minutes indicating the polypeptide nature of the ASF. Serum ASF activity consists of at least two factors (A and B) as shown by concanavalin A-agarose affinity chromatography. ASF-A and -B represent nearly 75% and 25% of the total serum ASF activity. ASF-B is a glycoprotein as it binds with high affinity to concanavalin A. The sera of species such as man, goat, and rat possess ASF activity. PMID- 2222078 TI - Therapeutic intrauterine insemination (TII)--controversial treatment for infertility. AB - The literature on therapeutic intrauterine insemination (TII) is confused because of lack of homogeneity in case selection, differences in executing the procedural steps, and the manner of evaluating and reporting results. This review compares results from Norfolk with those in the English literature. Special emphasis has been placed on separately analyzing each step of the procedure and presenting results of different authors in a comparable fashion. Including all etiologic factors and types of cycles, the term pregnancy rate per cycle was 3% for Norfolk, 2.6% to 6.2% elsewhere. Patients receiving TII in stimulated cycles did significantly better than those receiving TII in natural cycles, in terms of total pregnancy rate per cycle (p = 0.002). In male factor infertility, term pregnancy rate per cycle was 1.1% in Norfolk, 4.7% to 6.2% elsewhere (perhaps because of stricter criteria in Norfolk). In cervical factor infertility, term pregnancy rate per cycle was 4.5% in Norfolk, 2.7% to 11% for others. For unexplained infertility, Norfolk had 5.8% term pregnancy rate per cycle for natural cycles, 8.3% for stimulated cycles. Best published prospective results were 23% for stimulated cycles. TII seems to have a very low efficiency rate judging from term pregnancy rates per cycle. There are clear data indicating the need for redefining the indications. PMID- 2222079 TI - Therapeutic insemination by donor (TDI) achieves high pregnancy rates in infertile couples regardless of male motile sperm density. AB - Therapeutic insemination by donor (TDI) was just as successful in achieving pregnancies in couples in whom the male counterparts had subnormal motile densities as in those with normal levels. All wives in this study had an infertility factor that was corrected and remained so for at least 8 months. Thus, motile density may not be a particularly good predictor of male fertility potential. PMID- 2222080 TI - Artificial insemination with fresh donor semen. AB - A review is given of the use of fresh donor semen for therapeutic artificial insemination. This includes a section on the legal, ethical, and psychological aspects as seen from the point of view of various cultures. Topics covered are the indications for donor insemination, the selection of donors, and the techniques in common use. The success rate is described together with the sex ratio of the neonates. Short mention is made of short-term office semen preservation and the obsolete technique of mixed husband-donor insemination. PMID- 2222081 TI - Cryopreservation of human semen. AB - A review is given of the techniques for the cryopreservation of human semen, including the preparation of cryoprotective media, the use of ampoules, straws, and pellets, and freezing and thawing techniques. The use of cryopreserved semen for therapeutic artificial insemination by donor is described. The advantages of cryopreserved semen over fresh donor semen mostly lie in the ability to exclude infections before use and the extra convenience, in spite of the lower success rate and increased cost. The recovery of sperm motility on thawing is described, as are other methods for assessing the degree of damage to the spermatozoa by the freezing procedure. The success rates reported by large semen banks are summarized. PMID- 2222082 TI - Is electroencephalography necessary in the evaluation of syncope? PMID- 2222083 TI - Medical education in ambulatory settings. PMID- 2222084 TI - Is long-term levothyroxine therapy safe? PMID- 2222085 TI - The present medical database needs reorganization. It's time for a change! PMID- 2222086 TI - The impact of medical therapy on hemorrhagic complications following coronary artery bypass grafting. PMID- 2222088 TI - Electroencephalography should not be routine in the evaluation of syncope in adults. AB - We reviewed the reports of all electroencephalograms obtained at the Nashville (Tenn) Veterans Administration Hospital from September 1987 to August 1989. Seventy-three patients were referred for evaluation of syncope or near syncope. Of these 73 patients, 10 (13.7%) had abnormal findings. Twenty-six patients were referred for other complaints similar to syncope (ie, blackouts, loss of consciousness, falling out, passing out, and fainting). Of these 26 patients, five (19.2%) had abnormal findings. We reviewed the medical records of the patients with abnormal findings and found that the final diagnosis or treatment of the syncope was affected by electroencephalogram in only one patient. These findings suggest that routine electroencephalography is not of significant value in the evaluation of syncope in adults. PMID- 2222087 TI - Risk of gastric cancer after gastric surgery for benign disorders. AB - The objective of this review was to evaluate published evidence for the association between gastric resection for benign disorders and subsequent cancer of the gastric remnant. We searched the literature through Medline (1970 to 1988) and through the references of relevant articles. Fifty-eight studies consisting of case series, uncontrolled surveys, and case control or cohort analyses were identified and critically assessed using defined methodological criteria. There were no consistent differences between the expected and observed number of cancers occurring within 15 years after gastric resection. However, all case control studies and seven of the eight cohort analyses, in which the prevalence of cancer was stratified by time since gastric resection, indicated a twofold to fourfold increase in the risk of gastric cancer in patients who survived 15 or more years after gastric surgery. We conclude that most studies of the association of gastric surgery with subsequent gastric cancer have relatively weak designs. Still, the repetitive demonstration of this association by different investigators using different research designs supports the hypothesis that gastric resection increases the risk of cancer in the gastric remnant. PMID- 2222089 TI - The influence of age vs peak serum concentration on life-threatening events after chronic theophylline intoxication. AB - To identify risk factors for the development of seizures and cardiac arrhythmias after chronic, unintentional theophylline intoxication we monitored the clinical course of 72 consecutive patients referred to a regional poison center with chronic theophylline intoxication (serum theophylline concentration, greater than or equal to 167 mumol/L after protracted use). The median age of the sample was 47.5 years (range, 4 days to 91 years). Median peak theophylline concentration was 239 mumol/L, with a range of 167 to 722 mumol/L. A life-threatening event (LTE) occurred in 28 patients (39%) that included seizures in eight and a major cardiac arrhythmia in 22. The median peak (theophylline) of patients who had an LTE vs those who did not was 235.8 vs 238.7 mumol/L. However, the median age of patients with an LTE compared with those without an LTE was significantly greater (70.5 vs 18.0 years). Stratification of data by chronologic age revealed a stepwise increase in the frequency of LTE with advancing years: patients more than 75 years old had a 16.7-fold greater risk of LTE than patients less than 25 years old (95% confidence interval, 3.56, 77.5) despite comparable intergroup median serum (theophylline). These data suggest the primary determinant of LTEs after chronic theophylline intoxication is chronologic age. Elderly patients have an inordinately greater risk of LTE than younger patients. Peak serum theophylline concentration cannot predict which patients with chronic theophylline intoxication will have an LTE. Finally, these data indicate that theophylline should be used cautiously and with frequent monitoring of serum theophylline concentrations in elderly patients. PMID- 2222090 TI - The prevalence of Helicobacter pylori in nonulcer dyspepsia. Importance of stratification according to age. AB - Helicobacter pylori (formerly Campylobacter pylori) is causally related to active antral gastritis and is highly associated with duodenal and gastric ulcers. However, the relationship of H pylori to nonulcer dyspepsia is less clear. We determined the presence of H pylori in unselected patients who were undergoing upper gastrointestinal tract endoscopy, and we found a prevalence of 37% in 110 patients with nonulcer dyspepsia that was similar to previous data. Patients with nonulcer dyspepsia who had H pylori were found to be significantly older than patients with nonulcer dyspepsia who did not have H pylori. In addition, when stratified according to age, we detected an increased prevalence of H pylori in patients with nonulcer dyspepsia with increasing age, similar to that reported for asymptomatic control populations. This finding casts doubt as to the causal role of H pylori for most patients with nonulcer dyspepsia and stresses the importance of considering epidemiologic factors, such as age, when evaluating the role of H pylori in specific disease states. PMID- 2222091 TI - Treatment of adult chickenpox with oral acyclovir. AB - Thirty-one late adolescents and adults with varicella were studied. Patients identified within 72 hours of varicella exanthem were offered open treatment with acyclovir (4 g/d), and those patients identified after 72 hours of exanthem were followed up but not treated. Twenty-two patients were treated with acyclovir. Nine patients were not treated. No severe complications occurred in any of the 31 patients. Minor complications, including prolonged fever, localized secondary infections, persistent cough, and prolonged fatigue were more frequent in the untreated group. If the acyclovir therapy was begun within the first 24 hours of varicella exanthem, then the rash and clinical illness were dramatically lessened. Treatment with oral acyclovir should be considered for varicella in adults who are identified within the first 24 hours of exanthem. PMID- 2222092 TI - The association of blood pressure levels and change in renal function in hypertensive and nonhypertensive subjects. AB - We compared the changes in serum creatinine levels over time after a mean follow up of 9.8 years in essential hypertensive (EH, n = 56) and control (n = 59) male veteran subjects. All subjects had normal serum creatinine levels (62 to 124 mumol/L) and "normal" urinalysis results on entry into the study. Subjects with comorbid renal diagnoses and diabetes mellitus were eliminated from the analysis. Although not statistically significant, the rate of change in the serum creatinine concentration over time was greater in the EH cohort compared with the control cohort (1.08 +/- 4.8 vs 0.027 +/- 3.5 mumol/L per year). The difference was especially marked in black EH subjects vs black control subjects (1.60 +/- 6.2 mumol/L per year vs -0.21 +/- 3.3 mumol/L per year). When age, race, body mass index, and a diagnosis of EH were entered into a logistic regression analysis, EH subjects had a statistically significantly greater rate of decline in renal function than did control subjects (1.5 +/- 8.3 mumol/L per year). When mean time-averaged systolic blood pressure for each subject was also included in the logistic regression analysis, only systolic time-averaged blood pressure was statistically significant (0.063 +/- 0.029 mumol/L per year). We conclude that in the absence of clinically detected parenchymal renal disease, EH subjects have a greater rate of decline in renal function than do nonhypertensive subjects. Time averaged blood pressure is predictive of the change in serum creatinine concentration not only in EH subjects but also in nonhypertensive subjects. Thus, preservation of renal function may require a blood pressure lower than the currently accepted normotensive range. PMID- 2222093 TI - Morbidity, mortality, and quality of life for patients treated with levothyroxine. AB - In a population study of 1462 middle-aged women initiated in 1968 and 1969 we identified 29 women treated with levothyroxine from 1 to 28 years. In a 12-year follow-up in 1980 and 1981 we investigated the subjects for end-point myocardial infarction, diabetes mellitus, stroke, cancer, and death (the status of 99.7% of the initial participants was established). The women treated with levothyroxine showed no increase in morbidity or mortality. Of the 24 women still receiving levothyroxine in 1980 and 1981, 22 had serum thyrotropin and triiodothyronine concentrations with-in reference limits. These individuals were compared with the 968 women from the population study having no history of thyroid disease, and appeared identical as to laboratory and clinical data, with the exception of a slightly higher body mass, taller stature, and lower serum cholesterol concentration. The treated group did not differ in a life quality estimate based on 19 questions regarding life satisfaction and sensory function. We conclude that the levothyroxine-treated woman suffers no side effects from her life-long therapy. PMID- 2222094 TI - Acute lead poisoning in nursing home and psychiatric patients from the ingestion of lead-based ceramic glazes. AB - To our knowledge, acute inorganic lead poisoning from single ingestions of lead compounds has been only rarely reported. During a 14-month period, we were contacted regarding eight instances of acute ingestions of liquid lead-based ceramic glazes by mentally impaired residents of nursing homes or psychiatric facilities participating in ceramic arts programs. While some ingestions did not cause toxic effects, some patients developed acute lead poisoning characterized by abdominal pain, anemia, and basophilic stippling of red blood cells. In the blood of several patients, lead concentrations were far above normal (4 to 9.5 mumol/L). Urinary lead excretions were tremendously elevated during chelation therapy, with one patient excreting 535.9 mumol/L of lead during a 6-day period, the largest lead excretion ever reported in a patient suffering from acute lead poisoning, to our knowledge. All patients recovered following supportive care and appropriate use of chelating agents. Lead-based glazes are commonly found in nursing homes and psychiatric facilities. We suspect that acute or chronic lead poisoning from the ingestion(s) of lead-based ceramic glazes may be an unrecognized but not uncommon problem among such residents. We urge physicians to take ingestions of lead-based glazes seriously and to consider the diagnosis of lead poisoning in nursing home and psychiatric patients who have participated in ceramic crafts programs. PMID- 2222095 TI - Lipoprotein and apolipoprotein levels in subclinical hypothyroidism. Effect of levothyroxine therapy. AB - To assess whether subclinical hypothyroidism is associated with changes in lipoprotein fractions, 13 patients maintained in a stable state of subclinical hypothyroidism for at least 3 months were studied prior to and 2 and 4 months following restoration of a euthyroid state with incremental levothyroxine sodium therapy. Thyrotropin levels ( +/- SEM) had decreased from 16.6 +/- 3.2 mU/L to 3.1 +/- 0.7 mU/L and 3.2 +/- 0.7 mU/L at 2 months and 4 months. At 2 months, levothyroxine treatment led to a decrease in levels of total cholesterol from 5.5 +/- 0.3 mmol/L (213 +/- 12 mg/dL) to 4.8 +/- 0.3 mmol/L (186 +/- 12 mg/dL), in low-density lipoprotein cholesterol (LDL-C) from 3.7 +/- 0.3 mmol/L (143 +/- 12 mg/dL) to 2.9 +/- 0.3 mmol/L (112 +/- 12 mg/dL), and in apolipoprotein B from 91 +/- 8 mg/dL to 74 +/- 7 mg/dL. At 4 months, levels of LDL-C and apolipoprotein B remained significantly lower than pretreatment values (2.9 +/- 0.2 mmol/L [112 +/ 8 mg/dL] and 75 +/- 6 mg/dL, respectively). While high-density lipoprotein cholesterol (HDL-C), HDL3-C, and apolipoprotein A-I were not significantly affected by levothyroxine therapy, there was a slight trend of increase in HDL2-C during levothyroxine substitution. There was also a tendency for a decrease in triglyceride levels from 1.3 +/- 0.2 mmol/L (115 +/- 18 mg/dL) to 0.9 +/- 0.1 mmol/L (80 +/- 9 mg/dL) at 4 months of levothyroxine therapy. Levels of HDL-C tended to decrease from 4.8 +/- 0.4 mmol/L (186 +/- 15 mg/dL) to 4.5 +/- 0.5 mmol/L (174 +/- 19 mg/dL) at 2 months and to 3.9 +/- 0.4 mmol/L (151 +/- 15 mg/dL) at 4 months. The LDL-C/HDL-C ratio also decreased from 3.3 +/- 0.3 mmol/L (128 +/- 12 mg/dL) to 2.9 +/- 0.5 mmol/L (112 +/- 19 mg/dL) and 2.5 +/- 0.3 mmol/L (97 +/- 12 mg/dL) at 2 months and 4 months, respectively. These results suggest that long-term levothyroxine therapy in patients with subclinical hypothyroidism is associated with a decrease in LDL-C and apolipoprotein B levels that are reflected in a trend of decreases in cholesterol/HDL-C and LDL-C/HDL-C ratios known to have a relationship with coronary artery disease. PMID- 2222096 TI - Mortality following hip fracture before and after implementation of the prospective payment system. AB - Recent studies of patients with hip fractures from two hospitals have suggested that the marked reduction in length of stay that occurred following implementation of the Medicare prospective payment system (PPS) resulted in decreased quality of care for these patients. To assess whether this change influenced mortality, we studied patients with hip fractures aged 65 years or older from a 20% sample of Michigan Medicare enrollees. There were 2130 such patients in the 2 years preceding (October 1981 through September 1983) and 2238 in the 2 years following (October 1984 through September 1986) implementation of PPS. Although the demographic characteristics of patients with hip fractures did not change after PPS, the mean length of stay (95% confidence interval) decreased by 4.4 (4.1 to 4.7) days. However, mortality in the year following the fracture did not change: 23.2% before PPS, 23.7% after PPS; rate difference of 0.5% (-2.0 to 3.0). This finding was consistently present within subgroups defined by patient demographic characteristics. Furthermore, when the analysis was restricted to patients treated in those hospitals with the greatest reduction in average length of stay following PPS (7.5 days, or 35%), there was no significant change in 1-year mortality. For those patients who were enrolled in Medicaid and not in a nursing home at the time of the fracture, there was no increase in the rate of nursing home residence 1 year after the fracture. Thus, the findings of this population-based study suggest that the key outcomes of postfracture mortality and nursing home residence were not affected by the implementation of PPS. PMID- 2222097 TI - Fast and effective treatment of malignant hypercalcemia. Combination of suppositories of calcitonin and a single infusion of 3-amino 1-hydroxypropylidene 1-bisphosphonate. AB - Seventeen patients with malignant hypercalcemia were treated with a combination of a single dose of 3-amino 1-hydroxypropylidene-1-bisphosphonate (APD [also known as AHPrBP or palmidronate disodium]) and salmon calcitonin given as suppositories for 3 days. To assess whether such a combined short treatment has a significant benefit leading to earlier normalization of the plasma calcium level than does APD alone, 17 additional patients matched for the type of tumor, initial plasma calcium level, urinary hydroxyproline level, and the dose of APD served as controls. All patients receiving the combination of calcitonin and APD achieved normalization of the plasma calcium level within 9 days, with a decrease from 3.22 +/- 0.90 mmol/L (mean +/- SEM) to 2.29 +/- 0.03 mmol/L. In the group receiving APD alone, the plasma calcium level normalized in only 14 of 17 patients by day 9. In the group receiving calcitonin and APD, the drop in the plasma calcium level occurred more rapidly, and the plasma calcium values were lower from days 2 to 4. This advantage was explained by the calciuric effect of calcitonin, as reflected by a significant decrease in the notional setting of renal reabsorption of calcium, reaching 2.16 +/- 0.06 mmol/L compared with 2.34 +/- 0.06 mmol/L in the group receiving APD alone. There were no side effects of both treatments, in particular neither flushing nor nausea induced by the suppositories of calcitonin. Clinical Improvement occurred after 2 days in the group receiving the combined treatment. In conclusion, the combined treatment is rapidly effective and safe in the treatment of patients with hypercalcemia, particularly when the notional setting of renal tubular reabsorption of calcium is increased and a rapid correction of the plasma calcium level is needed. PMID- 2222098 TI - Strategies to improve teaching in the ambulatory medicine setting. AB - Expansion of resident training in ambulatory medicine has created new challenges for faculty preceptors. Outpatient teaching is hampered by inadequate time and a reliance on methods of instruction that are more useful for the inpatient setting. Effective outpatient teaching requires an understanding of the objectives of ambulatory medical training and improved facility with teaching methods that accommodate the brief, impromptu nature of ambulatory teaching. In a hypothetical outpatient teaching encounter, the interactions between the patient, resident, and attending physician are dissected to reveal missed opportunities to teach and to explore alternative approaches to the educational process. These approaches include promoting the resident's role as the primary provider, developing a limited teaching agenda for each teaching encounter, focusing on the learner rather than on the diagnostic dilemma posed by the patient, and using questions, role modeling and observation with feedback to promote learning. PMID- 2222099 TI - Pregnancy in women with immune thrombocytopenic purpura. AB - Thirty-six women with immune thrombocytopenic purpura were studied during 37 pregnancies, and maternal characteristics with predictive value for the fetal platelet count were determined. Nine neonates were thrombocytopenic, with a platelet count of less than 50 x 10(9)/L in eight. Four of these nine neonates delivered to a subgroup of 31 mothers were studied prospectively; the frequency of thrombocytopenia in neonates of women with immune thrombocytopenic purpura was thus 13%. Only two of these nine neonates presented with hemorrhagic syndromes (two, petechial purpura; one, intracranial bleeding). The frequency of neonatal thrombocytopenia was higher in mothers with deep thrombocytopenia and in those who had not responded to corticosteroid treatment following diagnosis. No prognostic value could be assigned to the other maternal characteristics studied, such as a history of splenectomy, maternal treatment at the time of delivery, or the presence of platelet autoantibodies evaluated either with the platelet immunofluorescence test or the platelet Western blot immunoassay. PMID- 2222100 TI - Emergence of ciprofloxacin resistance in nosocomial methicillin-resistant Staphylococcus aureus isolates. Resistance during ciprofloxacin plus rifampin therapy for methicillin-resistant S aureus colonization. AB - We initiated a randomized, single-blinded trial of ciprofloxacin plus rifampin vs sulfamethoxazole and trimethoprim plus rifampin in the therapy for patients who underwent colonization with methicillin-resistant Staphylococcus aureus (MRSA). Patients who were colonized with MRSA received 2 weeks of either regimen. The study was terminated after the enrollment of 21 subjects due to the recognition of ciprofloxacin resistance in 10 of 21 new MRSA isolates during the last 2 months of the study. Five of the 10 patients with ciprofloxacin-resistant MRSA isolates had never received ciprofloxacin. Long-term (6-month) eradication had been achieved in only three of 11 ciprofloxacin plus rifampin and four of 10 sulfamethoxazole and trimethoprim plus rifampin recipients. The use of this new fluoroquinolone for the eradication of MRSA colonization is usually not effective and may risk the development of ciprofloxacin resistance in MRSA within the hospital environment. PMID- 2222101 TI - Vision screening in a primary care setting. A missed opportunity? AB - To determine the effectiveness of vision screening in a primary care setting, we administered a questionnaire and a vision test to 458 patients from a general medical clinic. Subjects were referred for complete ophthalmologic evaluation if they failed the vision test or met other "high-risk" criteria based on information contained in the questionnaire. Patient-initiated requests for eye examinations were also honored. A total of 169 patients were scheduled for eye examinations, and 148 actually underwent ophthalmologic evaluation. One hundred one of those examined were referred on the basis of the study criteria. "Serious eye disease" (cataract, glaucoma, diabetic retinopathy, or age-related macular degeneration) was diagnosed in 96 (95%) of these patients. Prompt surgical intervention was recommended in 27 (27%), and medical treatment was begun in 21 (21%). Of those with serious eye disease, 59% met the criteria by failing the vision test, while 69% met the high-risk criteria determined by the questionnaire. Of the 148 subjects who received ophthalmologic evaluations, 47 requested them. Serious eye disease was diagnosed in 23 (50%) of the 47 patients. None of these individuals required immediate surgery, and medical treatment for glaucoma was begun in eight (17%). These data suggest that screening for serious eye disease in a primary care setting is an efficient mechanism to use for the identification of patients with undetected ocular disorders that require follow up or treatment. PMID- 2222102 TI - Spontaneous pneumothorax in patients with acquired immunodeficiency syndrome treated with prophylactic aerosolized pentamidine. AB - Spontaneous pneumothorax is a known complication of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. To evaluate the possible pathogenesis and natural history of pneumothorax in patients receiving aerosolized pentamidine prophylaxis, we retrospectively reviewed 327 outpatients positive for human immunodeficiency virus receiving aerosolized pentamidine. There were 12 spontaneous pneumothoraces in this group of patients. Seventy-five percent of patients with pneumothorax had roentgenographic evidence of fibrocystic lung parenchyma and clinical evidence of active Pneumocystis pneumonia. The majority (83%) required chest tube evacuation. There was a 50% mortality rate associated with this complication. These findings suggest that spontaneous pneumothorax in patients treated with aerosolized pentamidine most commonly represents a prophylaxis failure associated with a high mortality rate. PMID- 2222103 TI - Deaths due to accidents and violence in two recent trials of cholesterol-lowering drugs. AB - The Helsinki Heart Study and the Lipid Research Clinics Coronary Primary Prevention Trial both reported higher rates of deaths due to homicides, suicides, and accidents in the groups receiving cholesterol-lowering agents compared with the groups receiving placebos. We examined these deaths in the active treatment arms of the two trials to determine if there were some readily explainable causes or if the cholesterol-lowering agents might be a factor. Our examination showed that the two homicides were victims, not offenders, and one had stopped treatment because of myocardial infarction 1 year before his death. Five of the eight suicides had dropped out of the trials and had not taken the cholesterol-lowering drugs for periods of months to years prior to committing suicide. Of the 10 deaths due to accidents, two were dropouts from the trials, three others had high blood alcohol concentrations detectable at autopsy, and another three reported a history of psychiatric symptoms and/or treatment prior to entry. When dropouts and known risk factors for these deaths such as alcohol intoxication and psychiatric histories are considered, little evidence remains to support the hypothesis that cholesterol-lowering drugs are causally associated with deaths due to homicides, suicides, and accidents in these trials. PMID- 2222104 TI - Eosinophilia-myalgia syndrome. Recognition of a distinct clinicopathologic entity. AB - The eosinophilia-myalgia syndrome is a newly described disorder related to the ingestion of L-tryptophan-containing products. Its presentation may mimic other disorders characterized by eosinophilia and muscle pain and/or weakness, but can be differentiated by certain characteristic laboratory and pathologic findings. We report two such cases, describe their features, and review similar syndromes. PMID- 2222106 TI - Acute renal failure due to ciprofloxacin. AB - Acute renal failure developed in three patients within a few days of starting ciprofloxacin hydrochloride therapy. An allergic interstitial nephritis was suggested by fever and eosinophiluria in one patient and by erythema multiforme in another. A kidney biopsy specimen confirmed this diagnosis in one patient. Renal function improved shortly after withdrawal of the drug in all three patients. Literature survey revealed an additional three patients with a similar complication. Allergic manifestations, such as fever or rash, were a feature in most reported cases. In view of this potential complication, renal function should be closely monitored in patients receiving ciprofloxacin therapy, especially if other potentially nephrotoxic drugs are prescribed concomitantly. PMID- 2222105 TI - Eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Analysis of four patients and implications for differential diagnosis and pathogenesis. AB - Four patients fulfilling the case definition for eosinophilia-myalgia syndrome are described, including one whose disease began in 1986. Each displayed a variety of symptoms: one suffered principally from myalgia and recovered spontaneously on discontinuation of L-tryptophan therapy; one exhibited progressive sclerodermiform skin changes, neuropathy, and myopathy; a third had prominent neuromuscular disease and sclerodermiform skin changes; and the fourth experienced profound weight loss, an axonal polyneuropathy, and perivascular lymphoid infiltrates simulating a lymphoma. Evidence of T-cell activation was present in peripheral blood and affected tissues during the clinically active progressive phase of disease. Among other manifestations pleural effusion, cutaneous vasculitis, joint contractures, and bloody diarrhea were observed. A history of L-tryptophan ingestion should be sought in patients with myalgia, fatigue, or the above outlined symptoms. PMID- 2222107 TI - Desensitization in the management of vancomycin hypersensitivity. AB - Vancomycin is the preferred antimicrobial agent in the treatment of methicillin resistant staphylococcal infections. One of the well-known hypersensitivity reactions to this agent is the "red-man syndrome," which is believed to involve drug-induced histamine release in certain individuals. Although rate and/or dose reductions may be effective in some cases, some hypersensitivity reactions necessitate the discontinuation of vancomycin. In this article one patient is described who developed vancomycin-associated reactions consistent with the red man syndrome despite having tolerated vancomycin administration previously. This case was managed by sequential increments in vancomycin administration over several days that allowed for therapeutic doses of the drug to be administered. Prior to desensitization, vancomycin administration at a lowered rate and dose was unsuccessfully attempted, despite the presence of combination antihistamine therapy. A loss of skin prick test reactivity to vancomycin was demonstrated after successful desensitization. This desensitization method may be useful in managing certain refractory cases of vancomycin hypersensitivity. PMID- 2222108 TI - Comparative yield of blood culture for fungi and mycobacteria. PMID- 2222109 TI - Liver alterations in acute pneumonia. PMID- 2222110 TI - Seroprevalence of human immunodeficiency virus in a state psychiatric institution. PMID- 2222111 TI - Doppler echocardiography diagnosis of right ventricular outflow tract obstruction. PMID- 2222112 TI - A smoke-free hospital in China. PMID- 2222113 TI - [Sodium diphenylhydantoin changes the concentrations of DNA and proteins in the cerebrum, cerebellum and liver]. AB - Sodium diphenylhydantoin (DFH-Na) is the drug of choice to control convulsive seizure disorders. Beneficial as well as adverse effects of DFH-Na have been reported to occur since 1938. Thus, the present article deals with the effect that 2.5, 5, 10, 15, 20 and 100 mg/kg/day (2.5, 5, 10, 15, 20 and 100) might cause on Cerebrum (C), Cerebellum (Cb) and liver (L) DNA [DNA] and Protein [Pr] concentration. Our results showed that: 1) DNA-C-14 (15, 20 and 100) were found decreased when compared to control (p less than 0.001) and [DNA]-C-30 (15, 20 and 100) as well (p less than 0.001). [Pr]-C-7, 14, 30 (2.5, 5, 10, 15, 20 and 100) showed no statistically important differences. 2) [DNA]-Cb-14 (15 and 20) were found lower than control (p less than 0.05) and [DNA]-Cb-30 (15 and 20) as well (p less than 0.05). [Pr]-Cb-14,30 (100) was found decreased (p less than 0.05). 3) [DNA]-L-14 (10, 15, 20 and 100) was found decreased when compared to control (p less than 0.001) and [DNA]-L-30 (10, 15, 20 and 100) as well (p less than 0.001). [Pr]-L-7, 14 and 30 (2.5, 5, 10, 15, 20 and 100) were found lower than control (p less than 0.05). A bimodal pattern of [DNA] of C. Cb and L was demonstrated to occur with i.p. injected DFH-Na. PMID- 2222114 TI - The distribution of thallous ion between blood cells and plasma at equilibrium. AB - We have investigated the distribution of thallous ions between plasma and blood cells in whole blood both in vitro and in vivo (rabbit whole blood) and in vitro (human whole blood). The means of the percentual distribution are within the range of 61.4 to 64.2 percent for cell packet and 35.8 to 38.6 percent for plasma (n = 50), which is in agreement with previous reports. No significant differences between the two species were found when the direct percentages were compared; however, significant differences appeared (p less than 0.01; dose range 1 to 40 micrograms ml-1) when the comparison was made in terms of the ratio:(formula:see text). As for the effect of dose, there is an an apparent disminution in the thallium retained by the cells as the dose increases. However, when the comparison is made in terms of the normalized values, the dose effect is null within the range 1 to 40 micrograms ml(-1). Finally, the observed ratio cell packet/plasma (between 2 and 3) suggests that in whole blood, at equilibrium, thallous ion is mainly distributed passively between cells and plasma. The biological significance of it is discussed. PMID- 2222115 TI - Mast cells and idiopathic lung fibrosis. AB - Mast cells are usually related with allergic reactions in the lung. This cells has a biochemical repertoire capable of modulate inflammatory reactions in this organ. The relation of this cell with idiopathic pulmonary fibrosis (IPF), has not been studied in depth. There is no agreement in which is the best technique for counting mast cells and what are the normal counts of these cells in the lung. We analyse some of the reported "normal values" and the differences within IPF and patients with nonfibrotic lung diseases. The results of the present study demonstrate that the largest population of mast cells in IPF patients were the interstitium (342 +/- 83 cells) compared with the nonfibrotic patients (31 +/- 8 cells), and almost equal in both groups of patients in the subpleural, peribronchiolar and perivascular areas. However, it is necessary to unify criteria, in order to define what the normal values for mast cells in the lung are. PMID- 2222116 TI - [The biology of the volcano mouse (N. a. alstoni). XXI. Reproductive capacity of wild females in 15 successive matings]. AB - This study comprises an investigation on the reproductive capacity of wild females of the volcano mouse (Neotomodon alstoni alstoni), in 15 successive matings. The neotomodon were captured in the Sierra del Volcan Ajusco (Cerro Pelado, Parres, D.F.). The animals were kept under environmental laboratory conditions, being fed ALBI-LAB pellets and tap water. The matings were performed from may 1985 to August 1988 by pairs and at random, during 12 days. The females were weighed on the day 1 of the mating; the young were sexed on the 7th day of life, and weaned at the 30th day of age. The results were: the mean of the percentages of pregnancy in the 15 matings was 39.6 +/- 3.0, being the highest percentages in Spring-Summer. The size of the litter varied from 1 to 6 young, with a mode of 3 and a global average of 2.7. The means of the percentages of survival at the first week of life and at weaning were 72.9 +/- 3.6 and 70.3 +/- 3.3, respectively. The proportion males-females was 1.2:1. There was not found a significant positive correlation between the weight of the mothers at day 1 of the mating and the size of the litter (r = 0.65, p less than 0.05). These results allow to conclude that in the laboratory the wild volcano mouse exhibits a high reproductive capacity, which demonstrates that this rodent posseses very positive qualities in order to make out of him a new experimental animal. PMID- 2222117 TI - [Modified procedure for screening anticonvulsants. Re-evaluation of sodium diphenylhydantoin and phenobarbital]. AB - A modified antiepileptic screening procedure to test anticonvulsant drugs is shown. Diphenylhydantoin sodium salt (DFH-Na) and phenobarbital (Phb) were tested throughout 8 h, at hourly intervals after a single oral drug intake in rats. Another group was tested at steady stage of DFH-Na during 7 days period. A single dose of DFH-Na was orally administrated to male and female rats (30 mg/kg) and after testing throughout 8 h: 0, 5, 28, 38, 52, 70 and 75% and 10, 18, 50, 35, 62, 50 and 70% protection against MES, was found. Only 20% protection was found in females to METsc test on the 6th and 7th h. However, 80, 60, 60 and 20% males were found protected against METsc test from the 4th to the 8th hour. Maximum blood serum levels were 2 micrograms/ml. Phenobarbital at doses 12 mg/kg in males and females as well showed: 30, 64, 66, 74, 84, 90, 40, 34% and 14, 36, 53, 41, 55, 70, 82 and 82% protection against MES, respectively. On the other hand, 60, 60, 46, 47, 94, 100, 80 and 20% and 80, 80, 46, 70, 60, 40, 80 and 20% of males and females were protected against METsc test, respectively. An average of 8 micrograms/ml and 12 micrograms/ml of Phb serum levels were found since the 1 to the 8th and 5th hours, correspondingly. A 28% protection of both male and female rats to MES test was found following 7 days of treatment with DFH-Na (30 mg/kg) treatment. Also an average of 10% female and males were found protected against METsc test. PMID- 2222118 TI - Influence of previous housing history on the toxicity of amphetamine in aggregate mice. AB - The lethality of d-amphetamine was studied in isolated and aggregated mice with and without previous habituation to the physical or to the physical and social environment of chronically aggregated social condition under which the toxic effects of d-amphetamine were tested. In animals without previous habituation to such environments, d-amphetamine's toxicity was greatly enhanced by social aggregation, as reported by several authors in the literature. It was found that mortality in the dose range from 5 to 90 mg/kg is mainly determined by the stimulation due to aggregation. Above 90 mg/kg, the mortalities in single and aggregated mice vary in parallel. Up from this dose, lethality is independent of the external stimulation. Previous experience with house sharing in aggregated conditions reduces aggregation mortality in proportion to the duration of the previous house sharing period. PMID- 2222119 TI - The sensitivity of rat uterus to serotonin in vitro is a late estrogenic response. AB - This study was designed to further characterize the sensitivity to serotonin of the isolated rat uterus. The contractile response to serotonin induced by the administration of estradiol was increased depending on the duration of estradiol treatment, reaching the maximal contractility when ovariectomized rats were treated for 48 hours. Pretreatment with actinomycin D 1 hour before estrogen administration completely blocked estrogen-induced uterine sensitivity to serotonin. These results indicate that the sensitivity of rat uterus to serotonin in vitro induced by estradiol is a response occurring in the late phase and mediated by genomic activation. Following estradiol-administration uterine sensitivity to serotonin was similar in ovariectomized and ovariectomized hypophysectomized rats, suggesting that in this response a pituitary factor is not required. The contractile responses to acetylcholine and oxytocin were not modified by estradiol; thus, estrogens induced specifically uterine sensitivity to serotonin. The present in vitro studies using pelanserin, a potent S2 antagonist, show that serotonin induced contractions in the rat uterus are mediated by interaction with S2-receptors, since pelanserin inhibited not competitively the contractile response to serotonin. PMID- 2222120 TI - Hemolysin as a marker for Serratia. AB - All Serratia marcescens strains (total of 33) of different sources were hemolytic including clinical strains previously classified as being nonhemolytic. DNA fragments of the two hemolysin genes hybridized with the chromosomal DNA of S. marcescens, S. liquefaciens, S. kiliensis, S. grimesii, S. proteamaculans, S. plymutica, S. rubridaea which were also hemolytic. The restriction pattern of the hemolysin locus differed in each strain. S. ficaria and S. marinorubra expressed a different hemolysin which was much smaller than the S. marcescens hemolysin since it diffused through dialysis membranes. The DNA of the latter strains did not hybridize with the S. marcescens hemolysin DNA probes. Some S. marcescens strains, S. kiliensis and S. liquefaciens also expressed in addition the small hemolysin. No hybridization was found with DNA of Escherichia coli, Salmonella typhimurium, Proteus mirabilis, Proteus vulgaris, Citrobacter freundii, Enterobacter cloacae, Klebsiella arerogenes, Klebsiella pneumoniae, Shigella dysenteriae, Yersinia enterocolitica, Yersinia pseudotuberculosus, Listeria sp., Aeromonas sp., Legionella sp. and a Meninococcus sp., indicating that the hemolysin DNA probes are specific for Serratia, or that the hemolysin genes occur rarely in genera other than Serratia. PMID- 2222121 TI - Stereoselective formation of a K-region dihydrodiol from phenanthrene by Streptomyces flavovirens. AB - The metabolism of phenanthrene, a polycyclic aromatic hydrocarbon (PAH), by Streptomyces flavovirens was investigated. When grown for 72 h in tryptone yeast extract broth saturated with phenanthrene, the actinomycete oxidized 21.3% of the hydrocarbon at the K-region to form trans-9,10-dihydroxy-9,10-dihydrophenanthrene (phenanthrene trans-9,10-dihydrodiol). A trace of 9-phenanthrol was also detected. Metabolites isolated by thin-layer and high performance liquid chromatography were identified by comparing chromatographic, mass spectral, and nuclear magnetic resonance properties with those of authentic compounds. Experiments using [9-14C]phenanthrene showed that the trans-9,10-dihydrodiol had 62.8% of the radioactivity found in the metabolites. Circular dichroism spectra of the phenanthrene trans-9,10-dihydrodiol indicated that the absolute configuration of the predominant enantiomer was (-)-9S,10S, the same as that of the principal enantiomer produced by mammalian enzymes. Incubation of S. flavovirens with phenanthrene is an atmosphere of 18O2, followed by gas chromatographic/mass spectral analysis of the metabolites, indicated that one atom from molecular oxygen was incorporated into each molecule of the phenanthrene trans-9,10-dihydrodiol. Cytochrome P-450 was detected in 105,000 x g supernatants prepared from cell extracts of S. flavovirens. The results show that the oxidation of phenanthrene by S. flavovirens was both regio- and stereospecific. PMID- 2222122 TI - Purification and characterization of a (R)-2,3-butanediol dehydrogenase from Saccharomyces cerevisiae. AB - A NAD-dependent (R)-2,3-butanediol dehydrogenase (EC 1.1.1.4), selectively catalyzing the oxidation at the (R)-center of 2,3-butanediol irrespective of the absolute configuration of the other carbinol center, was isolated from cell extracts of the yeast Saccharomyces cerevisiae. Purification was achieved by means of streptomycin sulfate treatment, Sephadex G-25 filtration, DEAE-Sepharose CL-6B chromatography, affinity chromatography on Matrex Gel Blue A and Superose 6 prep grade chromatography leading to a 70-fold enrichment of the specific activity with 44% yield. Analysis of chiral products was carried out by gas chromatographic methods via pre-chromatographic derivatization and resolution of corresponding diastereomeric derivatives. The enzyme was capable to reduce irreversibly diacetyl (2,3-butanediol) to (R)-acetoin (3-hydroxy-2-butanone) and in a subsequent reaction reversibly to (R,R)-2,3-butanediol using NADH as coenzyme. 1-Hydroxy-2-ketones and C5-acyloins were also accepted as substrates, whereas the enzyme was inactive towards the reduction of acetone and dihydroxyacetone. The relative molecular mass (Mr) of the enzyme was estimated as 140,000 by means of gel filtration. On SDS-polyacrylamide gel the protein decomposed into 4 (identical) subunits of Mr 35,000. Optimum pH was 6.7 for the reduction of acetoin to 2,3-butanediol and 7.2 for the reverse reaction. PMID- 2222123 TI - Characterization of Aeromonas salmonicida variants with altered cell surfaces and their use in studying surface protein assembly. AB - Aeromonas salmonicida variants were characterized for alterations in their cell surface structure and used to examine reconstitution of the surface protein layer (A-layer). Variants lacking outer membrane O-polysaccharide were devoid of A layer and excreted stainable floret-like material of the surface protein (A protein). One variant, showing partial loss of O-polysaccharide, was associated with a disrupted A-layer and excretion of some A-protein. Variants lacking A protein but possessing O-polysaccharide rapidly absorbed and concentrated sufficient excreted A-protein at the cell surface to coat the cells with a single confluent layer. Although differences in electrophoretic mobilities of A-proteins and O-polysaccharides from "typical" and "atypical" strains were evident, the different A-proteins and A-protein-deficient variants were interchangeable for reconstitution of a surface protein layer. No association of A-protein with cell surfaces of unrelated gram-negative bacteria was observed. PMID- 2222124 TI - [Update on the morbidity of psychiatric disorders in patients with AIDS: results of a clinical follow-up]. AB - A follow-up study after one or two years of treatment was carried out on 107 AIDS patients who were seen by the Consultation-Liaison Psychiatry Unit of the Ramon y Cajal Hospital. The sample was reduced to 52 patients (49%) mainly due to the lack of check-ups in 43% and to the death of 8% of the cases. 36% of patients suffered from Delirium or Dementia and these had the greater mortality rate. Grade IV patients and those with a diagnosis of Adjustment Disorders came to the check-ups most frequently. PMID- 2222125 TI - [Psychiatric complications related to AIDS infection: apropos of a case of hypomania]. AB - The psychiatric disorders related with HIV infection can take various and complex forms. One case of Hypomania in a drug abuser patient with HIV + is reported, and it is suggested that this virus may produce symptomatology indistinguishable from the functional disorders. PMID- 2222127 TI - [Effect of cephalic perimeter and temperature on the latency and amplitude of the P100 component of the visual evoked potential]. AB - Pattern reversal evoked potentials were recorded from 40 people (20 males and 20 females) in good health. Latency and amplitude of P100 as well as cephalic perimeter and temperature were measured. Both samples did not differ in age. Males had a greater cephalic perimeter (p less than 0.00001) and females had a greater temperature (p less than 0.05). Amplitude of P100 decreased with age. We did not obtain any relation among cephalic perimeter or temperature with P100 latency or amplitude. We conclude that the consideration of these measurements does not increase the sensibility of VEP. PMID- 2222126 TI - [Rehabilitation in old age: a neuropsychological perspective]. AB - We are revising some programs of cerebral activation in elderly people. The application criteria from a neuropsychological perspective are proposed. A change about the rehabilitation of all types of brain injuries and its prevention is needed in the professional's attitude. PMID- 2222128 TI - [Hemangioblastoma associated with syringomyelia and syringobulbia in a patient with rheumatoid arthritis]. AB - A 80-year-old woman with a 25-year history of seropositive, erosive rheumatoid arthritis (RA) presented with a neurological clinical picture consistent with cervical cord compression, secondary to a hemangioblastoma with medulla, cerebellum and spinal cord involvement, with associated syringomyelia and syringobulbia. We present a review of the literature remarking the low frequency of this tumor (1%-2% of all intracranial tumors) and its exceptional presentation over the age of 70. We have not been able to find no cases of hemangioblastoma associated with rheumatoid arthritis, thus, we think, this association may be casual. Nevertheless, it emphasizes the need for careful evaluation of patients with rheumatoid arthritis and neurological symptoms before ascribing them to complications due to the rheumatoid disease itself. PMID- 2222129 TI - Long-term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation. AB - We compared the effect of abrupt discontinuation of therapeutic doses of short half-life and long half-life benzodiazepines in 57 benzodiazepine-dependent patients (daily use, greater than 1 year). Despite the use of a mean daily dose of 14.1 mg of diazepam equivalents, there were notable residual symptoms of anxiety and depression present at intake (Hamilton Rating Scale for Anxiety score, 17.0; Hamilton Rating Scale for Depression score, 14.0). Benzodiazepine intake was stabilized for 3 weeks before double-blind assignment to placebo (n = 47), or continued benzodiazepine use (n = 10). Clinical assessments were performed daily, including benzodiazepine plasma levels. Depending on the outcome criteria used, anywhere from 58% to 100% of patients were judged to have experienced a withdrawal reaction, with a peak severity at 2 days for short half life and 4 to 7 days for long half-life benzodiazepines. Relapse onto benzodiazepines occurred in 27% of patients who were receiving long half-life benzodiazepines and in 57% of patients who were receiving short half-life benzodiazepines. Baseline predictors of relapse were nonpanic diagnoses, a higher benzodiazepine dose, and a higher Eysenck neuroticism score. A short half-life and higher daily doses were associated with greater withdrawal severity, as were personality traits, such as dependency and neuroticism, less education and higher baseline levels of anxious and depressive symptoms. Patients who were able to remain free of benzodiazepines for at least 5 weeks obtained lower levels of anxiety than before benzodiazepine discontinuation. These results provide a detailed picture of the symptoms, time course, and multidimensional determinants of the benzodiazepine withdrawal syndrome. PMID- 2222130 TI - Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper. AB - We compared the effect on withdrawal severity and acute outcome of a 25% per week taper of short half-life vs long half-life benzodiazepines in 63 benzodiazepine dependent patients. Patients unable to tolerate taper were permitted to slow the taper rate. Ninety percent of patients experienced a withdrawal reaction, but it was rarely more than mild to moderate. Nonetheless, 32% of long half-life and 42% of short half-life benzodiazepine-treated patients were unable to achieve a drug free state. The most difficulty was experienced in the last half of taper. Baseline personality, high Eysenck neuroticism, female sex, and mild-to-moderate alcohol use were found to be more significant predictors of withdrawal severity than the daily benzodiazepine dose or benzodiazepine half-life. These findings suggest that personality factors contribute significantly to the patient's difficulties with gradual benzodiazepine discontinuation of therapeutic doses of benzodiazepines. PMID- 2222131 TI - Controlled comparisons of clomipramine and fluoxetine in the treatment of obsessive-compulsive disorder. Behavioral and biological results. AB - Treatment with fluoxetine hydrochloride was compared with treatment with clomipramine hydrochloride in two groups of patients with obsessive-compulsive disorder using two different experimental designs. In the first group of 11 patients with obsessive-compulsive disorder studied using a randomized, double blind, crossover design, treatment with fluoxetine for 10 weeks was found to produce therapeutic effects similar to treatment with clomipramine for 10 weeks. There were significantly fewer total side effects reported during fluoxetine than clomipramine treatment. Drug tapering and placebo substitution in the 4-week crossover interval phase led to substantial relapses in obsessive-compulsive disorder symptoms and depression. Furthermore, responses to the second drug took as long to occur as responses to the first drug, although both drugs are thought to act by a common mechanism, serotonin uptake inhibition. A second group of 21 patients with obsessive-compulsive disorder that had been previously stabilized on clomipramine treatment with at least partial benefit were crossed over to fluoxetine treatment in a double-blind fashion. After 10 weeks of fluoxetine administration, most patients manifested behavioral rating scores of obsessive compulsive disorder and depressive symptoms that were comparable with precrossover ratings completed during clomipramine treatment. A significant exacerbation in obsessive-compulsive disorder and depression ratings as well as a similar lag in therapeutic efficacy were also noted in this second cohort of patients with obsessive-compulsive disorder. Platelet 5-HT concentrations were reduced 95% during both clomipramine and fluoxetine treatment periods. These results suggest that fluoxetine may represent a viable alternative to clomipramine in the treatment of obsessive-compulsive disorder, although further studies with larger sample sizes are needed. PMID- 2222132 TI - Atypical depression, panic attacks, and response to imipramine and phenelzine. A replication. AB - In an initial study with 120 patients with reactive mood and associated atypical symptoms, phenelzine sulfate was superior to imipramine hydrochloride and placebo. Since their response to phenelzine appears to be unique, this suggests that atypical depression may be a distinct subgroup of unipolar depressive illness. Unexpectedly, the benefit of antidepressants was limited to patients who also had spontaneous panic attacks. To help establish the validity of this syndrome, a new sample of 90 atypical depressives was studied. The clinical and demographic characteristics of the original and replication sample were virtually identical at baseline. In addition, the treatment response with either placebo, imipramine, or phenelzine was also indistinguishable in the two patient groups. The outcome in the replication study supports the hypothesis that this may be a distinct unipolar depressive subgroup. In the replication sample, a history of panic attacks did not appear to be a relevant predictor. We discuss the explanations for this discrepancy in the two patient samples. PMID- 2222133 TI - HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia. AB - Agranulocytosis develops in approximately 1% of patients with chronic schizophrenia treated with the atypical neuroleptic drug clozapine. Previous studies have not identified the mechanism or risk factors for this adverse reaction. Because of an observed association between Jewish ethnic background and the development of agranulocytosis in our patient sample treated with clozapine for refractory symptoms, HLA typing was performed in 31 patients (19.4% of whom had developed agranulocytosis). The HLA-B38 phenotype was found in 83% of patients who developed agranulocytosis and in 20% of clozapine-treated patients who did not develop agranulocytosis. Because B38 is part of a haplotype known to occur frequently in the Ashkenazi Jewish population, the frequencies of the combined alleles HLA-B38, DR4, and DQw3 were examined. The incidence of HLA-B38, DR4, DQw3 was significantly increased in patients with agranulocytosis (five of five patients) compared with control patients of Ashkenazi Jewish ancestry (two of 17 patients). These findings indicate that genetic factors marked by major histocompatibility complex haplotypes may be associated with the susceptibility of Jewish schizophrenic patients treated with clozapine to develop agranulocytosis. We postulate that gene products contained in the haplotype may be involved in mediating drug toxicity. PMID- 2222134 TI - Toward a scientific psychiatric nosology. Strengths and limitations. AB - A consensus is emerging that psychiatric nosology should become more "scientific." The application of the scientific method to psychiatric nosology has a number of important advantages, including (1) providing a clear criterion by which to evaluate nosologic proposals, (2) preventing rapid changes due to nosologic "fashions" not supported by research findings, (3) increasing the prestige and acceptability of our nosologic system to individuals outside of psychiatry, and (4) optimizing the reliability and validity of our diagnostic constructs. However, many critical issues confronting nosologists are fundamentally nonempirical and cannot be addressed by the scientific method. Examples of such issues include (1) disagreements about the proper construct for a psychiatric disorder; (2) the interpretation of results when different validators provide opposing answers; (3) defining how different syndromes must be to be considered subtypes of the same disorder, distinct disorders within the same overall category, or entirely independent disorders; and (4) the proper balance of reliability and validity. The optimal use of the scientific method in our nosologic process requires a recognition of both its strengths and its limitations. PMID- 2222135 TI - Is DSM-IV needed at all? PMID- 2222136 TI - Offspring of twins with schizophrenia. PMID- 2222137 TI - Use of antidepressants in schizophrenia: diagnostic problems. PMID- 2222138 TI - Psychiatric morbidity in research volunteers. PMID- 2222139 TI - National pathology manpower survey. PMID- 2222140 TI - Cutaneous vascular calcification with ulceration in hyperparathyroidism. PMID- 2222141 TI - Financial impact of a rapid CK-MB-specific immunoassay on the diagnosis of myocardial infarction. AB - The purpose of this study was twofold. First, we evaluated the financial impact of a rapid, monoclonal antibody-based CK-MB mass assay (Stratus, Dade Division, Baxter Laboratories, Miami, Fla) for the direct measurement of CK-MB in serum samples from 65 patients admitted to the coronary care unit with the possible diagnosis of acute myocardial infarction. Second, we evaluated retrospectively the Stratus assay and an activity assay (electrophoresis) for CK-MB in the following patient categories: acute myocardial infarction treated with and without thrombolytic therapy, angina, congestive heart failure, skeletal muscle trauma, and the acutely ill without acute myocardial infarction. The advantageous features of the Stratus mass assay were as follows. First, the laboratory was able to perform the assay more frequently because of the short assay time per specimen (less than 10 minutes) without additional personnel. This had a substantial impact on the clinician's ability to diagnose acute myocardial infarction and to move patients out of an intensive care unit at substantial financial savings to the patient, the hospital, or the third-party payer. Second, the Stratus assay was able to detect low levels of CK-MB (1 to 2 micrograms/L) in the presence of low total creatine kinase activity (less than 100 U/L). Third, the Stratus assay showed no interference due to very-high-total creatine kinase activities (greater than 100,000 U/L), CK-BB, macro-creatine kinase, and mitochondrial creatine kinase. PMID- 2222142 TI - The technicon H6000 analyzer discriminates chronic lymphocytic leukemia from other B-cell leukemias through automatic assessment of large unstained cells. AB - The separation of chronic lymphocytic leukemia of B-cell origin from other chronic B-cell leukemias is subjective, being largely based on the morphologic features of the lymphoid cells in the peripheral blood. The percentage of large unstained cells determined with a Technicon H6000 analyzer (an automated blood cell differential analyzer, Technicon Instruments Corp, Tarrytown, NY) was used as a cell volume variable in an investigation of 70 cases of chronic lymphocytic leukemia of B-cell origin and of other chronic B-cell leukemias. The significant degree of correlation between the percentage of large unstained cells and morphoimmunophenotypic diagnosis, although obtained for a relatively small number of cases, suggests that this method of cell volume analysis can be used to improve diagnostic reproducibility in chronic B-cell leukemia. PMID- 2222143 TI - An immunofluorescence study of cerebral malaria. A correlation with histopathology. AB - Histopathologic and immunopathologic features of cerebral malaria have been defined in a study of six autopsy cases with severe Plasmodium falciparum infection. In five cases, immunofluorescent studies demonstrated intense deposition of P falciparum antigen, IgG, and fibrin in cerebral vessels associated with the histopathologic finding of hemorrhage in the white matter of cerebrum and cerebellum regardless of the presence of parasitized erythrocytes in the cerebral vessels. Immunofluorescent study also demonstrated the extravascular deposits of P falciparum granular antigen associated with acute inflammatory lesion in cerebral tissue in one case. These findings suggested that the immunopathogenic mechanism may in some way play a role in the pathogenesis of cerebral malaria. PMID- 2222144 TI - A prospective necropsy study of arthritis in acquired immunodeficiency syndrome. AB - Thirty-two knee and 23 sternoclavicular joints from 35 subjects with acquired immunodeficiency syndrome were examined prospectively at necropsy. There were two instances of opportunistic infectious arthritis: one caused by Staphylococcus aureus, the other by Sporothrix schenckii. In five other subjects, para-articular bone was infiltrated by granulomatous or neoplastic sequelae of the human immunodeficiency virus infection. There was no immunohistochemical (p24 antigen) or other evidence for existence of a specific acquired immunodeficiency syndrome arthritis. PMID- 2222145 TI - Study of preneoplastic changes of liver cells by immunohistochemical and molecular hybridization techniques. AB - The status of hepatitis B virus DNA was investigated by in situ hybridization in multifocal areas of a noncancerous hepatitis B virus-associated cirrhosis. This liver exhibited a marked degree of dysplasia and adenomatous hyperplasia. The results of these studies were correlated with the histopathology and immunohistochemical stains for hepatitis B core and surface antigens. There was clear evidence of a marked reduction to absence of hepatitis B viral DNA by in situ hybridization and absence of HBc and HBsAg in the foci of liver cell dysplasia and adenomatous hyperplasia. These results support the hypothesis that liver cell dysplasia and adenomatous hyperplasia are preneoplastic in nature. PMID- 2222146 TI - Persistence of mucosal gastric carcinomas for 8 and 6 years in two patients. AB - A small gastric carcinoma was detected in a man, but he refused surgery. Eight years later, he was readmitted for a check-up, and a partial gastrectomy was performed. Pathologic examination revealed a well-differentiated adenocarcinoma restricted within the mucosa. In another man, an irregularly shaped, grossly depressed lesion indicating a malignancy was present at the gastric angle, and 6 years later he agreed to a partial gastrectomy. The lesion proved to be a well differentiated adenocarcinoma confined to the mucosa. Retrospective examination of the original biopsy specimen revealed a small area of adenocarcinoma, presumably overlooked at the initial examination. Thus, some gastric carcinomas of the well-differentiated type can grow at an extremely slow rate, without extensive spread or invasion. Findings in these cases contribute to knowledge of the biological behavior of gastric carcinomas. PMID- 2222147 TI - Solid and cystic ultimobranchial body remnants in the thyroid. AB - In this study we determined the incidence rate (89%) and characterized the morphology of ultimobranchial body (UBB) remnants found in 18 serially sectioned neonatal thyroid glands. Although UBB remnants are often referred to as solid cell nests, we found cystic features in 55%. Ciliated columnar cells were seen in 23%. One contained a large pseudo-papilla. The UBB cells had nuclei with features reminiscent of papillary carcinoma nuclei in that they were enlarged, oval, and contained finely dispersed chromatin when compared with follicular cell nuclei. Both papillary carcinomas and UBB remnants are common, occur as tiny, solid, or cystic thyroid entities in patients of all ages, may contain papillary structures, and share some common nuclear features. Therefore, it is important to include UBB remnants in the differential diagnosis of minute thyroid entities and to recognize their morphologic features. PMID- 2222148 TI - Tumor of the atrioventricular nodal region. A clinical and immunohistochemical study. AB - Autopsy specimens of 17 tumors of the atrioventricular nodal region were studied. Sudden death occurred in 14 children and adults; seven of these patients had a history of atrioventricular block or syncope. Three tumors were incidental findings in infants with other congenital anomalies; diaphragmatic agenesis, pulmonary hypoplasia, and Meckel's diverticulum in one patient; mitral atresia in one; and congenital hydrocephalus, ventricular septal defect, patent ductus arteriosus, coarctation of the aorta, and patent omphalovitelline duct in the third. Immunohistochemical stains demonstrated strong positivity for carcinoembryonic antigen in 13 of 13 cases, B72.3 antigen in 5 of 7 cases, and cytokeratin in 11 of 11 cases. Twenty control cases of mesothelioma and mesothelial hyperplasia were all negative for B72.3; one showed focal carcinoembryonic antigen staining. Ultrastructural analysis of one case demonstrated short rudimentary microvilli not characteristic of mesothelial cells. We conclude that so-called mesotheliomas of the atrioventricular nodal region are not of mesothelial origin, because of strong carcinoembryonic antigen positivity and occasional positivity with B72.3, as these antibodies react with glycoproteins found in endodermally derived tissue and generally not with mesothelial tissue. Conduction system tumors are most likely congenital rests of endodermal origin, can be associated with other congenital anomalies, and often cause symptoms of heart block and sudden death. PMID- 2222149 TI - Acalculus lymphoeosinophilic cholecystitis associated with interleukin-2 and lymphokine-activated killer cell therapy. AB - A case of unusual cholecystitis that developed on completion of interleukin-2 and lymphokine-activated killer cell therapy is described. A 62-year-old man was treated with interleukin-2 and lymphokine-activated killer cells for disseminated renal cell carcinoma. During the course of the immunotherapy, his serum alkaline phosphatase level increased, as did the peripheral eosinophil count (0.31). Subsequently, clinical and radiologic evidence of acute cholecystitis was noted. The removed gallbladder showed acalculus cholecystitis with extensive diffuse infiltrates of numerous eosinophils and T lymphocytes, but sparse polymorphonuclear leukocytes. The authors name this unusual cholecystitis acalculus lymphoeosinophilic cholecystitis and believe it to be associated with interleukin-2 and lymphokine-activated killer cell therapy. The pathogenic relationship is discussed. PMID- 2222150 TI - Pulmonary blastoma with malignant melanoma component. AB - Pulmonary blastomas are rare primary tumors that consist of tubular or glandular structures embedded in an undifferentiated mesenchymal stroma. Focal cartilage, bone, and skeletal muscle as well as squamous differentiation have been described in these tumors. We report a unique case of a pulmonary blastoma showing a malignant melanoma component. Immunohistochemical stains for S100 protein and HMB 45 were positive in the areas of melanocytic differentiation. PMID- 2222152 TI - Human genome project. PMID- 2222151 TI - Neonatal intracranial choriocarcinoma. AB - A 1-month-old infant died from extensive intracerebral hemorrhage due to a metastatic choriocarcinoma to the brain that presumably originated in the placenta. The clinical course was characterized by hyperbilirubinemia, repeated episodes of seizures, and intracranial hemorrhage. A computed tomographic scan revealed a large vascular mass in the left parieto-occipital region and a small lesion in the left frontal lobe. The placenta was expelled during the delivery and was not examined. In view of the high level of maternal human chorionic gonadotropic hormone and the autopsy finding of metastasis, we presumed that the mass was a metastatic choriocarcinoma that had originated in the maternal placenta. To our knowledge, only one previous instance of this phenomenon has been reported. PMID- 2222154 TI - Functional assessment scales: a study of persons with multiple sclerosis. AB - The purpose of this study was to investigate disability in persons with multiple sclerosis (MS) by using combinations of functional assessment scales and subscales to predict (1) the burden of care measured in minutes of assistance provided per day by another person in the home, and (2) the subject's level of satisfaction with life in general. The Functional Independence Measure (FIM), Incapacity Status Scale, Environmental Status Scale, and the Barthel Index had high intercorrelations with each other. Although each was predictive of the MS subject's physical care needs, the FIM was the most useful. A change in total FIM score of one point was equivalent to an average of 3.38 minutes of help from another person per day. With the Brief Symptom Inventory and the Environmental Status Scale, the FIM contributed to predicting the patient's general satisfaction as well. We propose that burden of care and subjective satisfaction with life be the standards by which functional assessment instruments are compared to reflect, in pragmatic terms, the impact of disability on the lives of individuals and on the human and economic resources of the community. PMID- 2222153 TI - Physiologic responses to prolonged electrically stimulated leg-cycle exercise in the spinal cord injured. AB - This study determined the physiologic responses to prolonged functional neuromuscular stimulation (FNS) leg-cycle exercise in seven quadriplegic and seven paraplegic subjects. Each subject completed 30 minutes of continuous FNS leg cycling during which open-circuit spirometry, impedance cardiography, auscultation, and fingertip capillary blood sampling were used to assess metabolic and hemodynamic responses. Compared with resting values, oxygen uptake, carbon dioxide production, respiratory exchange ratio (RER), pulmonary ventilation, heart rate (HR), left ventricular stroke volume (SV), cardiac output (Qt), and blood lactate (La) concentration were significantly (p less than .05) elevated, whereas plasma volume, bicarbonate concentration, and pH were significantly decreased in both groups during prolonged FNS leg-cycle exercise. Mean arterial pressure remained unchanged in quadriplegic and paraplegic subjects during the prolonged FNS leg-cycle exercise bout. Persons with quadriplegia elicited significantly lower MAP and tended to have lower SV and Qt responses than persons with paraplegia, probably due to a higher degree of sympathetic dysfunction and circulatory hypokinesis during FNS leg-cycle exercise. All other physiologic variables responded similarly between groups. We speculate that the relative increases observed for HR (33% to 60%), SV (45% to 69%), and Qt (113% to 142%) during prolonged FNS leg-cycle exercise create a sufficient cardiac-volume load to promote central cardiovascular conditioning in persons with both quadriplegia and paraplegia. The La accumulation (4.7 to 5.2 mmol.L-1) in the spinal cord injured during prolonged FNS leg cycling is unusually high for the power output attained (5.2W and 6.1W for quadriplegia and paraplegia, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222155 TI - Rehabilitation of chronic stroke patients: changes in functional performance. AB - Forty stroke patients who were at least one year post-onset completed a one-month intensive rehabilitation program. The month before the program served as a control period. During the program, patients received individual sessions in occupational and physical therapy four days a week, and they participated in group activities on the fifth day. Therapy emphasized instruction in motor planning, balance and weight shift, and the use of adaptive equipment; these motor abilities were then practiced within real life situations. The patients demonstrated significant improvement in the outcome measures of weight shift, balance, and ADL scores after the one-month rehabilitation program (weight shift: F = 16.1, p = .0001; balance: F = 6.26, p = .0007; ADL: F = 13.8, p = .0001). They retained these new skills during a three-month follow-up period. PMID- 2222156 TI - Predicting inpatient rehabilitation length of stay. AB - Using standardized forms and predefined criteria, information was collected on all 1,238 patients admitted to the inpatient rehabilitation facility at our university hospital between August 1, 1980 and December 30, 1986. Data from 96% of these patients were used retrospectively to create a mathematic model, based on multiple linear regression, that predicts the patient's total rehabilitation length of stay (LOS). The model requires only information about the patient's admitting diagnosis, referral source, admission functional status, and date of admission. The model compared favorably with prospective estimates of LOS made independently by attending physicians at admission to rehabilitation. We conclude that such models could be used to facilitate management of rehabilitation units, forecast patient census, schedule unit personnel, set interim goals for LOS, and facilitate discharge planning. The delivery of rehabilitation services, like the delivery of other medical services, can be defined in part by objective, measurable patient characteristics. PMID- 2222157 TI - Manual stretch: effect on finger movement control and force control in stroke subjects with spastic extrinsic finger flexor muscles. AB - This study evaluated the effects of manual stretch of extrinsic finger flexor muscles on finger extension movement control and force control in 16 spastic hemiparetic subjects. These subjects were randomly divided into a control group and an experimental group. A group of able-bodied subjects also participated. A joint-movement tracking test (JMTT) quantified control of active finger extension movement at the metacarpophalangeal joint of the index finger within the available range of active movement, and a force tracking test (FTT) quantified control of isometric finger extension force at the same joint within the subject's available force range. Electromyographic activity was monitored in the extensor digitorum and flexor digitorum superficialis muscles during both tracking tests. Manual stretch was applied to the extrinsic finger flexor muscles of the experimental group between the pretest and posttest tracking tests. The JMTT performances of both control (p less than .025) and experimental (p less than .05) groups were significantly subnormal on the pretest as were FTT performances of controls (p less than .01) and study subjects (p less than .03). The JMTT improvement on posttest was significantly greater (p less than .05) in subjects than in controls. However, the change in FTT performance was not significantly different between the two groups. Manual stretch treatment, properly applied to extrinsic finger flexor muscles, is an effective method of temporarily improving the control of finger extension movement in spastic hemiparetic subjects. PMID- 2222158 TI - Long-term function of persons with atherosclerotic bilateral below-knee amputation living in the inner city. AB - Long-term function of 24 elderly persons with atherosclerotic bilateral below knee amputation living in an inner city for at least six months after the second amputation, was determined. Twenty-one (87.6%) subjects were living at home; three were living in nursing homes. Fourteen (70%) of 20 subjects who received bilateral prostheses were ambulators. At interview, the mean age was 75.2 years; 4.87 years was the mean time since the second amputation. Ten (50%) subjects remained ambulatory. Among the other ten who received prosthesis, loss of ambulation occurred mostly due to medical factors, at an average of 3.47 years after the second amputation. Those no longer ambulatory were older and "sicker," and the interval between amputations was shorter. Fifteen (62.5%) subjects were independent in dressing, 14 (58.4%) in toileting, and only nine (33.3%) in bathing. All but one subject required housekeeping assistance. The anticipated effect on function of environmental and socioeconomic factors could not be demonstrated in this sample. Survival time and retention of ambulatory skills for an average of nine years after the second amputation in eight (33.3%) subjects who died before the end of the study was longer than previously described. The high rate of success in rehabilitation and in maintenance of ambulatory skills fully justifies intensive restorative efforts for this group of amputees. PMID- 2222159 TI - A technique for quantifying and determining the site of isometric muscle fatigue in the clinical setting. AB - We investigated a clinically applicable technique for quantifying and determining the site of fatigue during isometric contraction. We measured torque in the right knee extensors of 17 able-bodied subjects during an isometric contraction for 60sec at 100%, 75%, 50%, and 25% of maximal effort. During contractions, a 0.5 sec train of 50-Hz stimulation was applied at 15, 30, and 45sec. We measured the percent decline in force over 60 sec (fatigue index) and average augmentation in torque during stimulation (AVAUGTORQ). The mean fatigue index at full effort was 25.1%. The mean AVAUGTORQ at 100%, 75%, 50%, and 25% of maximal effort was 12.1%, 26.3%, 40.5%, and 69.7% of values at complete relaxation, respectively. These methods should be clinically useful for quantifying the level of isometric fatigue, determining the site of fatigue, and measuring the level of effort in subjects without neuromuscular disease. The results agree with previous studies reporting a peripheral site of fatigue in healthy, well-motivated subjects. PMID- 2222160 TI - Kinematics of high-heeled gait with consideration for age and experience of wearers. AB - The purpose of this study was to determine whether the biomechanical accommodations to high-heeled shoes varied with age and experience in wearing high-heeled shoes. A t-test analysis was undertaken of the differences between low- and high-heeled gait in angles of rotation of the knee, hip, pelvis, upper trunk, and trunk. Biomechanical accommodations in gait caused by high-heeled shoes varied between younger and older individuals and between experienced and inexperienced wearers of high-heeled shoes. Younger subjects tended to increase lordosis of the trunk at heelstrike during high-heeled gait (1.7 degrees, SD = 0.8 degrees), whereas older subjects tended to flatten the trunk (-3.7 degrees, SD = 4.7 degrees, p less than .05). Experienced wearers had much greater increases in knee flexion during stance phase of high-heeled gait (5.3 degrees, SD = 3.3 degrees) than inexperienced wearers (1.9 degrees, SD = 1.9 degrees, p less than .05). Exaggerated upper trunk rotations were found in older and inexperienced subject groups rather than younger, and experienced groups (p less than .05). PMID- 2222161 TI - Strapless oral-nasal interface for positive-pressure ventilation. AB - A custom-fabricated strapless oral-nasal interface (SONI) is described. It was used in the long-term administration of intermittent positive-pressure ventilation (IPPV) by 18 patients with paralytic or restrictive pulmonary insufficiency. This interface is an acrylic shell which is firmly fixed to an orthodontic bite plate; it is designed to form a seal over the nose and mouth for the entry of IPPV. Eight patients were ventilator dependent 24 hours a day. The ten patients who required only nocturnal aid had improvement in daytime arterial blood gases. Although nine of these patients could manage less than 15 minutes of unassisted breathing (free time) supine, all slept supine on SONI IPPV. The 13 patients who underwent sleep monitoring maintained a mean oxygen saturation of 95.3% +/- 1.7% and acceptable end-tidal pCO2 (30 to 45 mmHg). These 13 patients have used SONI IPPV for an average of 22 months (range = 3 to 63 months). Impediments to successful long-term use of a SONI include the presence of a hyperactive gag reflex or stimulation of excessive oral secretions. When combined with mouth IPPV, glossopharyngeal breathing, the intermittent abdominal pressure ventilator, or the cuirass ventilator for daytime use, SONI IPPV is an option for the patient who prefers total ventilatory support by noninvasive means. PMID- 2222162 TI - Stroke rehabilitation: a geropsychological perspective. AB - Rehabilitation medicine and geriatric medicine are similar in their concern for functional improvement in the face of chronic medical conditions. Although many patients served by rehabilitation medicine fall within the geriatric age range, a knowledge of normal aging does not necessarily inform clinical decision making or research practices in rehabilitation. Using stroke as an example of a disorder affecting primarily geriatric patients and requiring the technology of rehabilitation, ways in which age might affect assessment of outcome are examined. Three areas dealing with conceptual and methodologic issues- depression, neurochemical interventions, and family--are highlighted. The final section outlines recommendations for research on rehabilitation outcome of geriatric stroke patients. PMID- 2222163 TI - Childhood stroke after minor neck trauma: case report. AB - Cerebral infarction after minor trauma to the neck has rarely been reported. A case is presented of a child with trauma to the vertebrobasilar artery resulting in stroke. Computerized tomography scan and angiography results are presented. Despite two subsequent, separate transient episodes of vertigo, the child had good functional recovery with complete restoration of language and cognitive function. After 28 months, residual impairments identified were a mild right sided ataxia and hemiparesis. PMID- 2222164 TI - Accreditation. Procedures and staff support for the Surgery Residency Review Committee. AB - The purpose of this article is to give an overview of the accreditation procedures of the Residency Review Committee for Surgery and provide insight into the nature and functions of staff support for the committee. In the process, a better understanding of how the Residency Review Committee itself carries out its tasks should also emerge. What is described here is specific to the Residency Review Committee for Surgery and should not be generalized to other residency review committees. PMID- 2222165 TI - Forty years of the RRC in Surgery. PMID- 2222166 TI - Humanism and the profession of surgery in the era of medical perestroika. PMID- 2222167 TI - Is arterial proximity a valid indication for arteriography in penetrating extremity trauma? A prospective analysis. AB - Three hundred seventy-three patients with a penetrating extremity injury were studied to assess the yield of arteriography. Patients underwent arteriography if any of the following was present: bruit, history of hemorrhage or hypotension, fracture, hematoma, decreased capillary refill, major soft-tissue injury, or nerve or pulse deficit. In the absence of these findings, arteriography was performed if the injury was in "proximity" to a major neurovascular bundle. In 216 patients, arteriography was performed when an abnormal finding was noted. Sixty-five injuries were identified, 19 requiring intervention. Proximity was the indication for arteriography in 157 patients. Seventeen injuries were identified, of which one required repair. In penetrating extremity trauma, the need for arteriography is based on clinical findings. The use of arteriography to screen for an arterial injury when proximity alone is the indication rarely identifies a significant injury and should be abandoned. PMID- 2222168 TI - Comprehensive management of acute necrotizing pancreatitis and pancreatic abscess. AB - Achieving reduced mortality rates in patients with necrotizing pancreatitis and pancreatic abscess is possible by employing a comprehensive management plan. Components of the plan include (1) rapid evaluation and assessment of the degree of physiologic and anatomic derangement, the latter by the prompt use of vascular enhanced computed tomographic scan; (2) adequate fluid resuscitation determined by early institution of advanced hemodynamic monitoring; (3) attempts to identify and document septic foci via computed tomography-guided percutaneous aspiration; and (4) aggressive surgical debridement. Close adherence to these policies allowed us to keep mortality in this seriously ill group of patients to 14%. Most deaths occurred in patients who were referred to this service late in the course of their disease. The Acute Physiology and Chronic Health Enquiry (APACHE) II severity of illness index applied at the time of admission proved an accurate predictor of mortality. A score of 25 or greater was highly predictive of death, and a lesser score, of survival. PMID- 2222169 TI - Immediate breast reconstruction following mastectomy is as safe as mastectomy alone. AB - We evaluated wound complications and potential risk factors after mastectomy with immediate breast reconstruction and compared them with similar data after modified radical mastectomy. The incidences of infection, seroma, hematoma, and epidermolysis were compared among 395 patients (305 with modified radical mastectomies and 90 with mastectomy with immediate breast reconstruction) from Virginia Mason Medical Center, Seattle, Wash, between 1983 and 1989. Obesity, age (60 years or older), smoking, antibiotics, and wound drainage were examined as possible risk factors. There were more wound complications in the modified radical mastectomy group (48% vs 31%), and specifically, more seromas (30% vs 13%). In the modified radical mastectomy group, age of 60 years or older was associated with seroma and infection, drainage greater than 30 mL per day (at time of drain removal) with seroma, and smoking with epidermolysis. In the mastectomy with immediate breast reconstruction group, obesity was associated with seroma and epidermolysis. We conclude that mastectomy with immediate breast reconstruction appears to be as safe as modified radical mastectomy alone with respect to wound complications. PMID- 2222170 TI - Blunt intestinal injury. Keys to diagnosis and management. AB - Fifty-six patients with blunt intestinal injury seen during 39 months were reviewed for keys to diagnosis and treatment. Motor vehicle accidents were involved in 80% of the cases and seat/lap belts were in use 69% of the time. Blunt intestinal injury was the only abdominal injury in 70% of the cases. There were 42 perforations and 20 devascularizations; multiple injuries were common (27%). Abdominal tenderness was present on admission in 43 of 44 patients in whom a reliable examination was possible. Peritoneal lavage was positive in 13 (93%) of 14 patients. Computed tomography was falsely negative in three of four instances in which it was used. Perforations were most common in the upper and lower ends of the small bowel and in the sigmoid colon; devascularizations were most common in the distal ileum and sigmoid colon. Resection/anastomosis was performed in 38% of small-bowel perforations and in all small-bowel devascularizations. Resection/diversion was required in most colonic perforations (five of six patients) and devascularizations (four of six patients). There were five deaths (9%), none due to intestinal injury. There were seven complications related to intestinal injury. Diagnostic delay occurred in two patients; both had resultant morbidity. Blunt intestinal injury is associated with physical findings in conscious patients. Peritoneal lavage should be used when tenderness cannot be evaluated. Timely operative intervention minimizes morbidity and hospital stay. PMID- 2222171 TI - The operative management of coexisting thyroid and parathyroid disease. AB - Three hundred eight patients who underwent operation for hyperparathyroidism were studied. Fifty-two (17%) were identified who had a concomitant thyroid nodule. All 52 underwent parathyroidectomy and thyroid resection in a single operation. Eleven of these patients (21% of those with a thyroid nodule) had differentiated thyroid cancer. One patient with parathyroid hyperplasia developed permanent hypocalcemia. None had permanent vocal cord paralysis and none required tracheostomy. Thorough visual inspection and palpation of the entire thyroid gland should be performed during operations for hyperparathyroidism. Incidentally discovered thyroid nodules should prompt formal lobectomy with frozen section diagnosis; unanticipated thyroid malignancies should then be treated as independent entities. Treating simultaneous hyperparathyroidism and nodular thyroid disease with a single operation can be done safely; it avoids the expense and risk associated with neck reexploration and can detect unsuspected cancers. PMID- 2222172 TI - The efficacy of central venous and pulmonary artery catheters and therapy based upon them in reducing mortality and morbidity. AB - The purpose of this study was to (1) evaluate the relative cost effectiveness of the central venous pressure and flow-directed pulmonary artery catheters used to maintain normal hemodynamic values as therapeutic goals in the control groups vs supranormal values empirically observed in critically ill postoperative survivors in the protocol groups, and (2) to evaluate tissue perfusion and oxygenation in relationship to organ failure and mortality. In two prospective clinical trials there were no significant differences in outcome between the central venous pressure and pulmonary artery control groups that used normal values as therapeutic goals. However, there were marked and significant reductions in morbidity and mortality of the protocol groups using the supranormal cardiac index, oxygen delivery, and oxygen consumption values as goals. The cumulative oxygen debt was less and organ failures were fewer and less severe in the protocol groups than in the control groups. PMID- 2222173 TI - Popliteal vascular trauma. A community experience. AB - Preventing amputation continues to be a significant challenge when popliteal vascular injuries occur. A retrospective review of cases from the San Diego County (California) Trauma System identified 108 patients with 76 blunt and 32 penetrating arterial injuries. The limb preservation rate was 88%; there were 13 amputations. The fracture-dislocated knee injury and close-range shotgun blasts were particularly limb threatening. In general, the trauma system achieved rapid evaluation of injuries and early operative intervention. All 13 patients who underwent amputations presented with signs of severe ischemia. Concomitant injuries to the popliteal vein, tibial nerves, and soft tissue were significantly more frequent in patients who underwent amputations. The importance of complete fasciotomy for compartment hypertension, early reconstructive management of soft tissue injuries, and expeditious arterial repair, frequently without preoperative roentgenographic suite arteriography, is emphasized. An aggressive, multidisciplinary approach is required to achieve a functional extremity when popliteal vascular trauma occurs. PMID- 2222174 TI - Utility of computed tomography for surveillance of small abdominal aortic aneurysms. Preliminary report. AB - To assess the ability of computed tomography to predict the potential for expansion of small abdominal aortic aneurysms, we analyzed the computed tomographic scans of 30 patients who had two or more abdominal computed tomographic scans at least 6 months apart between 1979 and 1989. Clinical variables and 10 defined objective characteristics of computed tomography were evaluated. Twenty-five men and five women with abdominal aortic aneurysms ranging from 30 to 64 mm (mean, 45 mm) were followed up with serial computed tomographic scans for a mean (+/- SE) of 26 +/- 3 months. In 19 patients, enlargement of aneurysm diameter of 3 mm or more on serial computed tomographic scans was noted, whereas in 11, there was little or no expansion. Of the clinical variables studied, only serum cholesterol correlated with an increased risk of expansion. Thrombus area, measured by computed tomography, was 7.3 +/- 0.9 cm2 in enlarging aneurysms vs 4.3 +/- 0.9 cm2 in stable aneurysms. Based on these preliminary data, we conclude that computed tomography may provide valuable information about the likelihood of future expansion of small abdominal aortic aneurysms. PMID- 2222175 TI - Treatment of traumatic rupture of the thoracic aorta. A 15-year experience. AB - Traumatic rupture of the thoracic aorta is increasing in incidence and remains a highly lethal injury. The morbidity associated with this injury also remains high. We retrospectively reviewed the records of all patients admitted to our emergency department with ruptured thoracic aortas during a 15-year period to determine the reason for this persistently high morbidity and mortality and to identify any factors that might improve the outcome. We found that patients who are in unstable condition on arrival in the emergency department or who become unstable before reaching the operating room are not likely to survive. Patients who are injured in automobile accidents have a greater chance of survival than do those injured in motorcycle accidents or car-pedestrian accidents. Patients who are in hemodynamically stable condition after aortic injury survive only if diagnosis and treatment are prompt. Major complications of repair following thoracic aortic injury relate primarily to the length of cross-clamp time, and every effort should be devoted to keeping the cross-clamp time less than 30 minutes. PMID- 2222176 TI - Angioscopy for intraoperative management of thromboembolectomy. AB - Our experience with angioscopy suggests that direct visualization of the arterial lumen during thromboembolectomy procedures would provide a more reliable method of assessing luminal morphologic characteristics than angiography alone. We inspected 32 grafts (seven aortobifemoral, 18 infrainguinal bypass, and seven dialysis access fistula grafts) in 32 patients. Thirty-one patients had thrombotic events and one patient had an acute embolus. Angioscopy following standard catheter thrombectomy revealed significant amounts of retained thrombus or neointima in all thrombectomies. Angioscopic information from 18 patients with an infrainguinal bypass graft led to graft revision in six cases and placement of a new graft in 10 cases. One graft limb was replaced in seven aortobifemoral grafts, and multiple repeated thrombectomies were employed to extract debris in the remaining six cases. Repeated graft thrombectomy was also beneficial in dialysis access fistulas. Angioscopy allowed us to omit the completion angiogram and led to an improved technical result. We conclude that angioscopy is useful during thromboembolectomy procedures. PMID- 2222177 TI - Massive splenomegaly. Superior results with a combined endovascular and operative approach. AB - Splenectomy for massive splenomegaly (drained splenic weight, greater than 1000 g) has an uncommonly high morbidity and mortality because of technical challenges and problems of hemostasis. In a group of 10 patients with massive splenomegaly due to myeloproliferative disorders (average splenic weight, 4193 g), we developed a management algorithm based on preoperative angiographic embolization of the splenic artery. Average operating time was 1.7 hours (range, 1 to 2.5 hours). Average blood loss was 528 mL; six of the 10 patients had blood loss less than 250 mL. There were four minor complications and one major complication (gastric ulcer requiring reoperation). There were no deaths in the perioperative period, and no patients required reoperation for hemorrhage. PMID- 2222178 TI - The recalcitrant perineal wound after rectal extirpation. Applications of muscle flap closure. AB - Perineal wounds developing after abdominoperineal resection result in chronic purulent drainage and intermittent episodes of sepsis and are generally unresponsive to conservative medical and surgical treatment. Thirteen consecutive patients (aged 27 to 74 years; mean, 48 years) who underwent debridement and immediate muscle flap closure of these wounds were analyzed to identify risk factors for delayed healing and to evaluate the effectiveness of muscle flap coverage. Three risk factors were identified: preoperative or postoperative radiation therapy, resection for recurrent carcinoma, and inflammatory bowel disease. A total of 19 muscle flaps (11 gracilis, five gluteal thigh, two gluteus maximus, and one rectus abdominis) were used to close these wounds. During an average 3.5-year follow-up, four (31%) minor complications and one (8%) recurrence were noted to occur. Muscle flaps provide safe, effective, single stage procedures for the closure of chronic perineal wounds. PMID- 2222179 TI - Selection factors resulting in improved survival after surgical resection of tumors metastatic to the lungs. AB - From 1973 through 1987, a total of 140 patients underwent 184 operations for removal of metastatic tumors to the lungs. The number of lesions removed ranged form one to 30. Of the patients, 44% had solitary lesions. Overall 3-year survival was 62.6%, and 5-year survival was 48.2%. In all primary tumors except melanoma and breast cancer, 3-year survival was greater than 50% and 5-year survival was greater than 40%. With rare exceptions, the operation of choice for unilateral lesions was ipsilateral thoracotomy, and for bilateral lesions it was median sternotomy. Adequate conservative resection was the rule. There were three pneumonectomies, 25 lobectomies, 71 single wedge resections, 38 multiple unilateral wedge resections, and 47 bilateral wedge resections. There were no postoperative hospital deaths. Cox covariate analysis demonstrated improved survival in patients whose largest lesion was less than 1.5 cm in diameter and with disease-free interval longer than 1 year, but survival was not related to number of lesions or age of patient. An aggressive surgical approach is justified in patients with most primary tumors and a limited number of lung metastases less than 1.5 cm in diameter. Resection of metastases from melanoma and breast cancer should be accomplished after other sites of metastatic disease have been ruled out by the most stringent criteria. PMID- 2222180 TI - Heterotopic tissue in lymph nodes. An unrecognized problem. AB - Heterotopic tissue in lymph nodes is both unknown to clinicians and a potential source of confusion with metastatic disease. We reviewed the English literature and found 289 cases of heterotopic tissue in lymph nodes. The majority (84%) of these patients were operated on for malignant neoplasms. The most frequent sites of occurrence was the pelvis (67%), followed by the axilla (14%), neck (14%), groin (3%), abdomen (2%), and mediastinum (less than 1%). The tissue seen is site specific and frequently resembles a neighboring organ. Three cases have been reported in which heterotopic tissue was mistaken for metastatic disease. These cases illustrate the importance of being familiar with heterotopic tissue in lymph nodes and identifying it when it does occur, to avoid inappropriate therapy. PMID- 2222181 TI - Reoperative surgery for the morbidly obese. A university experience. AB - Patients who undergo surgery for morbid obesity are often subjected to reoperation for a wide array of indications. To evaluate outcome following revisional procedures, we reviewed the records of 32 such patients treated at UCLA between April 1986 and May 1989. Twenty-five women (78%) and 7 men (22%) with a mean age of 44 years underwent 76 reoperations (2.4 per patient) for complications of prior obesity surgery. Indications for initial surgical revision consisted primarily of metabolic derangements (12 patients) and weight-related problems (11 patients). In contrast, indications for the patients' final surgical procedure were commonly for bowel obstruction (41%), intra-abdominal sepsis (12%), and gastrointestinal bleeding (6%). Following initial revision, 23 patients (71.8%) required further surgery for major complications and four patients died (12.5%). While initial revisions are frequently indicated for metabolic problems, final reoperations are more frequently undertaken for urgent, life-threatening complications. Revisional procedures for morbid obesity should be carefully considered, and the potential for major complications and/or death should be weighted heavily against proposed benefits. PMID- 2222182 TI - Electron microscopy of mouse thymic virus. AB - Thymuses of mice infected with mouse thymic virus (MTV), a herpesvirus, were examined with the electron microscope. Damage was manifested by distortions of cells, nuclei, and other organelles, with cellular aggregation apparent at advanced stages of necrosis. Infected cells also contained MTV particles and filaments. Negative staining showed that naked MTV capsids were icosahedral in shape with diameters ranging from 95 to 110 nm. Enveloped capsids appeared spherical and ranged in diameter from 125 to 165 nm. Immunogold labeling revealed the presence of antigenic sites around both naked and enveloped capsids, and also on the 10 nm filaments. The use of electron microscopy and immunohistochemical techniques as diagnostic tools to demonstrate MTV infection could prove valuable for the detection of the infection and the study of its pathogenesis. PMID- 2222183 TI - Implication of mitochondria in the replication of Nodamura virus in larvae of the Lepidoptera, Galleria mellonella (L.) and in suckling mice. AB - The replication of Nodamura virus, type species of the family Nodaviridae, takes place principally into the interfibrillar spaces of the sarcoplasm in close association with mitochondria in the infected muscles of both G. mellonella and suckling mice. The most striking event in infection of G. mellonella muscle cells was the aggregation and shape modification of numerous mitochondria (elongation, interdigitation, and vesiculation) at an early stage of infection. These clusters of mitochondria were cemented by a thick electron-dense material at the periphery of which viral particles undergo maturation process. In a later stage, degenerated and dilated mitochondria showed a clear assembling of virus particles on their outer membrane and occasionally on some inner membranes. These facts and the localization of RNA by RNase-gold technique in the assembling sites of viruses around and inside the mitochondria allowed us to postulate a role for the mitochondria as supports and/or energy suppliers for viral RNA synthesis and translation. PMID- 2222184 TI - Replication of two porcine parvovirus isolates at non-permissive temperatures. AB - Previous studies have shown that replication in vitro of the porcine parvovirus (PPV) isolate, KBSH, was restricted at 39 degrees C but not at 37 degrees C. In contrast, replication of the Kresse isolate was restricted at 37 degrees C but not at 39 degrees C. In this study, Kresse and KBSH isolates were passaged up to ten times in swine testicle (ST) cells at non-permissive temperatures, and at subsequent passage viral protein synthesis, viral DNA synthesis, and progeny virus were evaluated. KBSH became adapted for replication at 39 degrees C upon serial passages, displaying an appreciable increase in viral progeny, viral polypeptides, and viral DNA concentration. This finding was also observed with Kresse virus isolate continuously passaged at 37 degrees C. Neither isolate became adapted for replication at 32 degrees C. In an attempt to examine the effect of in vitro passage at non-permissive temperatures on pathogenicity in swine, KBSH passaged 10 times either at 37 degrees C or 39 degrees C was inoculated into swine fetuses. Two of four fetuses inoculated with 39 degrees C passaged KBSH were dead and hemorrhagic or mummified. All four fetuses inoculated with 39 degrees C-KBSH contained viral antigen and viral DNA. In contrast, fetuses inoculated with 37 degrees C-passaged KBSH, or with cell culture fluid were normal in appearance. Viral antigen and viral DNA were not demonstrated in fetuses inoculated with 37 degrees C-KBSH or cell culture fluids. These findings suggest the possibility that the ability to replicate at 39 degrees C is associated with virulence in swine fetuses. PMID- 2222185 TI - Characterisation of an avian influenza virus nucleoprotein expressed in E. coli and in insect cells. AB - The nucleoprotein (NP) gene from influenza virus A/Shearwater/Australia/72 has been expressed intracellularly in both E. coli and insect cells. E. coli-derived NP was identified by Western blot analysis as a 56 kDa protein which co-migrates with virion-derived NP. This protein was purified by immunoaffinity chromatography and a nitrocellulose binding assay showed that NP formed complexes with positive- and negative-sense influenza neuraminidase RNA transcribed in vitro. ELISA and Western blot analysis revealed that recombinant NP of 56 kDa was produced in high yields in insect cells using a baculovirus vector. Immunofluorescence microscopy revealed that NP was localised to the nucleus of infected insect cells. PMID- 2222186 TI - Priming effect of recombinant vaccinia virus coding for the middle hepatitis B surface antigen. AB - Recombinant vaccinia virus expressing the middle hepatitis B virus surface antigen was incapable of inducing marked antibody response against the S and pre S2 antigenic specifities in mice. However, mice immunized with this virus produced antibodies to both these antigens after the following administration of subtreshold doses of plasmatic hepatitis B surface antigen. PMID- 2222188 TI - Antigenic stability of H3 influenza viruses in the domestic duck population of southern China. AB - An antigenic analysis was carried out on 145 duck influenza virus isolates of the H3 haemagglutinin subtype obtained over five years continuous surveillance from the region of southern China, a hypothetical influenza epicentre. This was done using a panel of twelve monoclonal antibodies raised to an early human strain of the H3 subtype. We demonstrate the existence of an extensive range of antigenic profiles, broadly similar but not identical to the human H3 strain, which persisted over the five year period. This variability was as great during discrete twelve month periods as over the whole five years. Hierarchic progression (observed with human strains) was not evident and no correlation of antigenic drift, in either positive or negative direction, was observed with the domestic duck isolates over time. Changing dominant antigenic profiles were, however, observed in faecal isolates with time within a single farm. The much broader range of profiles detected in pond water samples from the same farm suggested the existence of a heterogeneous antigenic reservoir. Local switching of dominant profiles may occur due to changes of cohorts as birds are taken to market. In vitro and in vivo passage experiments revealed a high degree of heterogeneity in antigenic profiles in progeny of uncloned isolates, whereas the profiles of cloned isolates were largely conserved. These results suggested that particular antigenic profiles in primary isolates may result from mixtures of subpopulations of the wild type virus in natural duck infections. Switching between reactivity profiles of different progeny is likely to be largely a result of regrouping of these subpopulations with lesser effects due to mutation. Hypervariability in some of the cloned isolates was observed with a few monoclonal antibodies recognising a region of HA reported to be hypervariable in swine influenza virus. Reactivity with one particular antibody was correlated with passage in chicken eggs. The ability of this enormously varied pool of duck influenza H3 strains to cross the species barrier to man and give rise to viruses with hierarchic capabilities was considered. PMID- 2222187 TI - Immunogenic properties of ISCOM prepared with influenza virus nucleoprotein. AB - After covalent attachment of bacterial lipopolysaccharide to the nucleoprotein of influenza A virus, this water-soluble antigen could be incorporated firmly into ISCOM. This potent "immunostimulating complex" induced the production of high antibody titers in mice and could partially protect the animals from a lethal challenge infection. After immunization with ISCOM preparations NP-specific cytotoxic T cell activity could not be demonstrated. PMID- 2222189 TI - HTLV-I antibody studies in villagers in East Sepik Province, Papua New Guinea. AB - Serum samples collected in 1984 during a malariometric survey of two villages in the East Sepik Province of Papua New Guinea were tested for antibodies to HTLV-I. None of the villagers showed any symptoms suggestive of retrovirus infection. Eighteen of the 186 (9.5%) sera tested at that time were found to be positive. Blood samples were subsequently obtained from fifteen of the eighteen positives and subjected to analysis by enzyme-linked immunosorbent assay (ELISA), radioimmuno assay (RIA), radioimmunoprecipitation assay (RIPA), and Western blot (WB). Fourteen of the fifteen gave a positive ELISA response, but none were unequivocally positive by p 24 RIA. All sera tested were reactive to gag antigens by WB, but gave "indeterminate" results currently accepted criteria. Notably absent from the WB profiles of all of the study subjects was an antibody response to HTLV-I envelope protein gp 46. It is possible that these antibody responses are directed against a variant of HTLV-I or to a novel retrovirus which possesses core antigens similar to those of HTLV-I but has different envelope antigens. Until a virus is isolated, or the viral genome is identified in infected lymphocytes, the possibility remains that the response may be due to factors unrelated to retrovirus infection. PMID- 2222192 TI - Anti IgE-induced asthma in guinea pigs; a new model for asthma. Physiological and pathological studies. AB - We established an experimental animal model for IgE-mediated asthma by the use of intravenous injection of rabbit anti guinea pig IgE in normal guinea pigs. The degree of asthmatic airway obstruction was quantitatively estimated by Mead's apparatus which enabled us to use unanesthetized guinea pigs. With the injection of anti IgE, only an early asthmatic response was observed. Inhalation of anti IgE did not trigger asthma. Histo-pathological changes in the lung obtained immediately after the injection of anti IgE resembled those reported in human asthma. This system may be used for pathological and pharmacological studies of the IgE-dependent early asthmatic response. PMID- 2222190 TI - Localization of nucleocapsid associated polypeptides in measles virus-infected cells by immunogold labelling after resin embedding. AB - The nucleo-, phospho- and matrix protein of measles virus were localized at high resolution within infected cells by use of post-embedding immunogold labelling techniques. In general, labelling with monospecific antibodies as well as with a polyvalent rabbit anti-measles hyperimmune antiserum revealed measles virus polypeptides to be distributed non-randomly within infected cells with the label largely confined to specific sites, namely inclusions of nucleocapsids and assembled virus structures at the plasma membrane. Immunogold double labelling indicated that the phosphoprotein strictly co-localized with the nucleoprotein in cytoplasmic inclusions of nucleocapsids and in budding virions, whereas intranuclear inclusions of nucleocapsids were devoid of phosphoprotein labelling. Antibodies to the matrix protein clearly labelled assembled virus structures at the plasma membrane but exhibited no significant cytoplasmic or intranuclear reaction. The data indicate that the composition of nucleocapsids varies with the cellular compartment with which they are associated, supporting the view of a rapid assembly of paramyxovirus nucleocapsid polypeptides, and emphasize the proposed selective role of the matrix protein in virus assembly and budding at the plasma membrane. PMID- 2222193 TI - [Allergic individuals to Japanese cedar or orchard grass consist of two subgroups based on the sensitization to Dermatophagoides pteronyssinus]. AB - One hundred and twenty-six allergic subjects were divided into three groups based on the RAST results for Dermatophagoides pteronyssinus (D.p) and Japanese cedar (J.C.). We compared sex, age of examination for RAST, serum IgE, family history of allergic diseases, prevalence rate of bronchial asthma (BA) and allergic rhinitis (AR), and onset of AR among three groups. No significant difference in the other variables except serum IgE and prevalence rate of BA was found between the group with D.p-positive and J.C.-positive RAST and the group with D.p positive and J.C.-negative RAST. The group with positive RAST for D.p and J.C. showed lower age of the examination, higher serum IgE, higher incidence of allergic family history, higher prevalence rate of BA, and lower onset age of AR than the group with negative RAST for D.p and positive RAST for J.C. We suggested that in J.C. RAST-positive group there might be two different subgroups distinguished by RAST result for D.p Similar results were obtained from the assessment of RAST for Orchard grass instead of J.C. PMID- 2222191 TI - Characterization of a temperature-sensitive mutant in the RNA polymerase PB2 subunit gene of influenza A/WSN/33 virus. AB - The temperature-sensitive mutant ts-1 of influenza virus A/WSN/33 carries mutations in the gene encoding RNA polymerase PB2 subunit. Effect of temperature on various steps of viral RNA synthesis was examined using disrupted virions of ts-1 mutant. The initiation of RNA synthesis with dinucleotide ApG primer was not affected by elevated temperature, whereas that with primer RNA containing 5' terminal cap-1 structure was temperature-sensitive. The result supports the previous notion deduced from the UV-crosslinking experiments, that PB2 is involved in the cap-1 dependent initiation of RNA synthesis. In addition, the ts 1 mutant showed a defect in RNA chain elongation. Nucleotide sequence analysis of RNA segment 1 of ts-1 mutant revealed that the amino acid number 417 is essential for the recognition of cap-1 structures and/or the interaction with catalytic unit of the RNA polymerase. PMID- 2222194 TI - [The relationship between respiratory threshold to acetylcholine and prognosis for asthma]. AB - Forty nine asthmatic children were studied to clarify the relationship between the respiratory threshold of acetylcholine (RT-Ach) and the prognosis for asthma. In those patients who had asthmatic attacks fewer than 60 days in the last year, there was a statistically significant relationship between RT-Ach and the number of the days of asthmatic attacks over the 6 and 12 month periods following the inhalation test. In the younger group (5-11 years old), there was a statistically significant relationship between RT-Ach and the number of the days of asthmatic attacks over the 6 and 12 month periods following the inhalation test. However, in the elder group (12-15 years old), no such relationship was recognized. In the elder group, the obstructive index, one of the indices of flow-volume curve, had a statistically significant correlation with the number of asthmatic attacks over the 6 and 12 month periods following the inhalation test. However in the younger group, no such relationship was recognized. PMID- 2222195 TI - [The effects of various drugs and immune complexes on the function of alveolar macrophages from patients with collagen-vascular diseases with interstitial pneumonia]. AB - Alveolar macrophages (AM) taken from sixteen patients with collagen-vascular diseases with interstitial pneumonia (CVD-IP+) were cultured with prednisolone (PSL), prostaglandin E2 (PGE2), colchicine (Colch), D-penicillamine or aggregated IgG (agg-IgG). The culture supernatants were tested on the fibroblast proliferation function and the amounts of fibronectin (Fn) and interleukin 1 (IL 1). The fibroblast proliferation was suppressed significantly by the supernatants of AM cultured with PGE2. The Fn production by AM was significantly suppressed by PGE2 and Colch. The IL-1 production by AM was not suppressed by these drugs, but was enhanced by Colch. In five patients with CVD-IP+, the fibroblast proliferation of AM supernatant was enhanced by agg-IgG. In these five patients, Fn and IL-1 production had a tendency to be increased by agg-IgG. The ratio of immune complexes (IC) in broncho alveolar lavage fluids to those in sera was significantly higher in patients with CVD-IP+ than in patients with CVD without IP suggesting a local production of IC in the lung in the patients with CVD-IP+. PMID- 2222196 TI - [A case of mixed connective tissue disease developed into overlap syndrome of progressive systemic sclerosis, systemic lupus erythematosus, polymyositis and Sjogren's syndrome]. AB - We encountered a patient who developed an overlap syndrome of progressive systemic sclerosis (PSS), systemic lupus erythematosus (SLE), polymyositis (PM) and Sjogren's syndrome (SjS) while we were treating her for mixed connective tissue disease (MCTD). This 42-year-old woman had been photosensitive since 18 years of age. In 1986, Raynaud's phenomenon, swollen hands and arthralgia appeared; therefore, we started to treat this patient based on a diagnosis of MCTD. At that time, her anti-RNP antibody titer was 82,920, but she was negative to anti-Sm antibody. In 1988, she was admitted to our hospital with chief complaints of aggravation of polyarthralgia and myalgia. On physical examination, she showed difficulty in opening her mouth, systemic dermal sclerosis, a decrease in muscular strength and rales. In laboratory tests, her myogenic enzyme level was increased, and she was found to be positive to LE cells, antinuclear antibody, anti-DNA antibody, anti-ENA antibody and anti-SSA antibody. Furthermore, histological features clearly corresponding to those of PSS were found by skin biopsy, myogenic changes by electromyography, evidence of chronic inflammation of the salivary glands by lip biopsy, and proliferative changes in the mesangium were detected by renal biopsy. The concept of MCTD, especially the differences from overlap syndrome, is vague. Therefore we need further study about many cases. Since there have been no reports on cases having sufficient evidence of the development of the overlap syndrome of PSS, SLE, PM and SjS during a course of MCTD, our patient would provide very useful data contributing to the study of MCTD. PMID- 2222197 TI - [Antigen-induced biphasic eosinophil infiltration in the airways of actively sensitized guinea pigs and its inhibition by PAF antagonist and cyclosporin A]. AB - Bronchial eosinophilia is a characteristic of asthma. To elucidate the mechanisms of eosinophil accumulation in the airways, the time course of eosinophil infiltration in the airway mucosa after antigen inhalation was examined in actively sensitized and passively sensitized guinea pig models of asthma. The lungs and tracheae were removed at intervals after antigen challenge, fixed and stained. The eosinophil infiltration was quantitated in the tracheal walls by counting the number of cells per square millimeter. Guinea pigs sensitized by intraperitoneal injection of ovalbumin (OA) responded to a single exposure to aerosolized OA with biphasic infiltration of eosinophils in the tracheal walls; a striking early-phase which peaked at 6 hr and a delayed-phase which peaked at 24 hr and persisted for as long as 5 days. These kinetics were different from those observed with passively sensitized animals which showed only early-phase infiltration. Administration of CV-6209, a specific PAF antagonist, before and 12 hrs after antigen challenge significantly (p less than 0.01) inhibited the early phase but not the delayed-phase eosinophil infiltration in actively sensitized animals. In contrast, when guinea pigs were treated with Cyclosporin A, a T lymphocyte-selective immunosuppressive agent, throughout the immunization period, the delayed-phase but not the early-phase infiltration was significantly (p less than 0.01) inhibited. These results suggest that PAF may contribute to early phase and T cell factor(s) may contribute to delayed-phase eosinophil infiltration of the airways. PMID- 2222198 TI - [Platelet-activating factor in Japanese cedar pollinosis]. AB - Japanese cedar pollinosis is a typical allergic disease and has recently become a big social problem. Many population are suffering from this disease every year from the end of February to the beginning of April. In this study, we planned to examine the role of platelet-activating factor (PAF) in this disease, because PAF has been known to be one of the potent chemical mediators in allergic and inflammatory reactions and many evidences indicate that PAF is deeply involved in the pathogenesis of bronchial asthma, a typical allergic disease. We measured the concentrations of the PAF derivative (lyso-PAF) in serum from patients with cedar pollinosis during the pollen season. The level of lyso-PAF in serum from untreated patients with cedar pollinosis (87.8 +/- 8.7 unit.) was significantly higher than that in healthy control (54.9 +/- 7.7 unit.). We also tested the effect of an anti-allergic drug on the level of serum lyso-PAF of cedar pollinosis. Eighteen pairs of serum samples from patients with cedar pollinosis were employed in this study. Lyso-PAF levels after two weeks' therapy with ketotifen (2 mg/day), an anti-allergic drug, decreased the levels significantly (from 82.6 unit to 41.3 unit). These results suggest that PAF could play some important role in cedar pollinosis and that the clinical effect of anti-allergic drug could be partially due to the anti-PAF action. PMID- 2222199 TI - Cloning and sequencing of cDNAs corresponding to mite major allergen Der f II. AB - A cDNA library corresponding to mite protein was screened employing anti-Der f II antibody. Two possible clones were obtained, which contained plasmids, pFL1 and pFL11, respectively. Both plasmids had insertions of about 500 base pairs. The DNA sequences of the two insertions were determined, from which the amino acid sequences were deduced. The amino acid sequence of the purified native Der f II protein could be determined to 45 residues from the N-terminus. As a result of comparison, we concluded that the cDNAs prepared from live mite Dermatophagoides farinae corresponded to the mite allergen, Der f II. PMID- 2222200 TI - [Morphofunctional changes in the hemo- and lymphomicrocirculatory bed of the uterus and its regional lymph nodes in venous congestion during pregnancy]. AB - Interrelations of the blood and lymphatic systems of the uterus have been examined in rats at pregnancy complicated with the ++phlebo-occlusive syndrome. Blood stream impediment in the caudal vena cava results in increasing diameter of the arterioles, capillaries and venules of the endo- and myometrium. Certain disturbances of blood circulation in the uterus at the ++phlebo-cclusive syndrome in the pregnancy animals, as a rule, reflect in the uterine lymph outflow; this is demonstrated as dilatation and deformity of the lymphatic vessels and capillaries, appearance of protrusions of the lymphatic vessels wall. There is a definite co-ordination in the reaction to the caudal vena cava occlusion in the intra-, ++extra-organic uterine lymphatic bed and in its regional lymph nodes, manifested as the following morphological signs: decreasing relative volume, that the lymphoid tissue occupies and increasing relative volume of the cortical and medullary intermediate sinuses. PMID- 2222201 TI - [Structure of lymphatic vessels in the rat thyroid gland]. AB - The lymphatic bed of the thyroid gland has been studied in 24 intact rats. Three techniques facilitating to reveal lymphatic vessels in the organ have been used: preparation of semithin sections, injection of the blood bed with methyl methacrylate with a successive chemical extraction of the preparations, injection of the blood bed with liquid solution of methyl methacrylate with a consecutive study of the preparations in the scanning electron microscope. Methods of electron histochemistry (revealing horseradish peroxidase) and kryofractography have been applied. Construction of the thyroid lymphatic bed, structure of the wall are described, fibroblastic membrane (F-membrane) is revealed and the signs are presented, that allow to differentiate F-membrane from endothelium of the lymphatic capillaries. The pathways of lymph outflow in the rat thyroid gland consist of the following links: interstitial space in the interlobular spaces of the gland, into them the tissue liquor (lymph) is filtered ; plates of the F membrane regulating direction of excessive albumin-containing liquor in the lymphatic capillaries, surrounding groups of 5-11 follicles, embracing the microlobule of the gland and situating in the interlobular spaces, deferent lymphatic vessels. PMID- 2222202 TI - [Transplantation of human embryonal nervous tissue to the spinal cord of mature rats]. AB - Pieces of the wall obtained from the anterior cerebral bladder of human embryos at the age of 8-10 weeks can survive in the spinal cord of mature animals. In the transplant, unlike the normal embryonal histogenesis, neuroepithelial cells make groups of rosellas. The differentiation process of cells of the human nervous tissue transplant can be followed in the rat spinal cord without any immune suppression up to the end of the 2d month of development. During the 3d month the transplant neuroblasts perish as a result of the immune reaction. PMID- 2222203 TI - [Aldehyde dehydrogenase activity in the rat brain during ontogenesis]. AB - By means of the quantitative histochemical method aldehyde dehydrogenase (1.2.1.3; AlDH) activity has been studied in the rat brain and spinal cord structures. AlDH activity (acetaldehyde is used as a substrate) in the barrier structures of the brain (vascular and villous ependymocytes of the cerebral ventricles, endothelium of blood capillaries) makes only 10-30% during the antenatal period and then increases gradually, reaching the activity specific for mature animals by the 20th-40th day after birth. Up to the 10th day of the postnatal development AlDH activity of neurocytes of various types makes 45-70%, and then increases sharply, and by the 20th day is approaches the definitive one. AlDH activity of the spinal cord motoneurons in old rats (2-year-old) essentially surpasses the control. In the white cerebral substance and its gliocytes from the 10th up to the 40th day after birth AlDH activity sharply increases; this coincides with myelinization of the CNS. Dynamics of aldehyde-oxidating ability is probably connected with natural changes in the CNS metabolism during ontogenesis. At the same time, it reflects a low level in stability of the developing brain to the damaging effect of exogenic ethanol and especially to its toxic metabolite--acetaldehyde. PMID- 2222204 TI - [Morphological characteristics of the thymus gland of albino rats after prenatal administration of indomethacin]. AB - By means of histological, histochemical and electron microscopical methods the thymus of white rat fetuses and offspring has been investigated during various age periods after indomethacin++ influence (2.5 mg/kg). In the fetuses retardation in separation of the gland parenchyma into lobules has been revealed. During the first two weeks of life the section area of the medulla decreases. Amount of lymphoid cells decreases; small and degenerating lymphocytes decrease in their number, while the part of lymphoblasts, middle lymphocytes and figures of mitosis increases. Enzymatic activity in the nervous structures of the organ is inhibited. Some essential disturbances of the intracellular structures are revealed; they demonstrate certain destructive changes. The data obtained show a decreasing function of the thymus after the prenatal influence of indomethacin++ during the first month of life, which is especially manifested during the first two weeks. PMID- 2222205 TI - [Classification of erythroblastic islets of the bone marrow and the study of their cellular composition]. AB - Cell composition of erythroblastic islands (EI), normal and at the phase of stimulation and inhibition of erythropoiesis at modelling of heat adaptation has been studied on hemopoietic tissue of 108 rats. In the hemopoietic tissue, together with EI of the 1st, 2nd and 3d classes of maturity, that have in their composition correspondingly up to 8, from 9 up to 16 and above 16 nuclei containing erythroid cells, there are involutive and reconstructing EI. The involutive EI are presented as nuclei-containing erythroid cells, that are not able to divide and are at late stages of differentiation: polychromatophilic and oxyphilic normoblasts, as well as reticulocytes. The reconstructing EI have in their composition both erythroid cells, that are not able to divide, and erythroid cells (pro-, erythroblasts and basophilic normoblasts), that are at early stages of differentiation. Application of the EI classification suggested, takes into account the rate, with which the erythroid cell-predecessors are drawn into erythropoiesis and intensity of erythroid differentiation. Therefore, it is possible to obtain earlier and more exact data on the state of hemopoiesis in comparison with traditional hematological methods. PMID- 2222206 TI - [Cytological structure of splenic white pulp in persons of different age]. AB - Spleens (27) obtained from human corpses (from 1 year up to 85 years) have been investigated. By means of morphometrical grid amount of cells in the periarterial lymphoid muffs (PLM) and in marginal zones (MZ) of the spleen have been counted. In both structures of the white pulp small lymphocytes make the greatest number. Middle lymphocytes in comparison to the small ones are 1.5-4 times less in most of the age groups investigated. Amount of plasma cells is small. The part of reticular cells is 21-46% in MZ and 20-36% in PLM from the total amount of cells. In PLM immediately around the artery tightly packed to each other small lymphocytes are situated. Among small lymphocytes reticular cells are situated. A similar arrangement of cells is kept along the whole thickness of PLM. In MZ distance between cells of the lymphoid line is a little greater than in PLM. To singularly situating reticular cells small and middle lymphocytes are immediate neighbours. Plasma cells, as a rule, occur seldom; either middle lymphocytes, or reticular cells adjoin them. Sometimes, in PLM and MZ macrophages occur; they are situated in the areas free from other cells. PMID- 2222207 TI - [Analysis of the ultrastructure of atrial cardiomyocytes in rats after alimentary dehydration]. AB - By means of water deprivation primary- and secondary-compensated and decompensated degrees of dehydration have been caused in 24 rats. Electron microscopical investigation has demonstrated a more pronounced granularity of cardiomyocytes in the left than in the right cardiac auricles. During the alimentary dehydration granularity of the atrial cardiomyocytes in the right auricles increases at the primary- and secondary-compensated degrees of dehydration, in the stage of decompensated dehydration it decreases, the character of distribution of the secretory granules, however, shows certain processes of exhaustion. Granularity of the atrial cardiomyocytes in the left auricles during alimentary dehydration of the organism does not change. Changes of the endocrine apparatus in the atrial cardiomyocytes occur against the background of microcirculatory disturbances in both auricles of the heart and are combined with dystrophic changes in cardiomyocytes. PMID- 2222208 TI - [Structure and cytophysiology of gastric endocrine gland cells after repeated administration of testosterone propionate]. AB - By means of light, electron microscopy and morphometry methods contents and structural organization of endocrinocytes have been investigated in gastric glands of rats, to whom testosterone propionate has been injected for 5, 10, 15, 20 days. The hormone produces certain stimulating effect on the endocrine apparatus function. During the first stages of the experiment most of the endocrinocytes are at the state of active secretion; this is testified as a decreasing composition of histochemically revealed cells in epithelium and their degranulation. During the following stages the process of synthesis is activated in the cells and their amount increases. Appearance of numerous agranular, poorly differentiated endocrinocytes and exo-endocrine cells demonstrates certain intensification of cytogenesis of endocrinocytes in the gastric epithelium. The changes observed are considered as adaptive, directed to stabilize homeostasis, when the hormonal balance is disturbed. PMID- 2222209 TI - [Reaction of the duodenum, renal parenchyma and their blood microvessels to external bile discharge in turtles]. AB - Morphological characteristics in rearrangement of the structural components of the duodenum, renal parenchyma and their hemomicrocirculatory beds are presented at a chronic experimental external bile discharge in the tortoise. Common reactions of microvessels in response to this experimental action, manifesting as their constriction and dilatation, depend, possibly, on general changes in the organism specific for the acholia state. Specific rearrangements, such as reduction of blood capillaries of the duodenal mucous membrane and appearance of polypous outgrowths in this place with successive ulceration should be considered as a reaction to a decreased level of the functional loading to these parts of the duodenum. PMID- 2222210 TI - [Kinetics of cell population of the jejunal mucosal epithelium in mice after administration of syngeneic lymphocytes]. AB - By means of the radioautographic method the state of cellular restoration of the gastric epithelium has been estimated after administration of syngenic lymphocytes to mice. Under conditions of physiological regeneration T-lymphocytes are able to inhibit proliferation of the epithelial cells and to limit the size of the proliferation zone in crypts. The inhibition degree of the proliferative activity depends on the doze of the T-cells administered. In order to demonstrate their activity, T-cells do not need DNA and RNA synthesis de novo. At the same time, protein synthesis is necessary; it occurs on long-living mRNA lymphocytes. The T-lymphocyte action is reversible at the tissue, but not at the cellular level. The mechanism of decreasing cell reproduction under effect of T lymphocytes is described. In the process of lymphoid regulation of the cellular restoration in the intestinal epithelium changes in the size of the proliferative pool play the main role. PMID- 2222211 TI - [Spermatogenic cycle in seals (Callorhinus ursinus L.)]. AB - In the fur-seal germ cells at various stages of development are situated in the spermatic canaliculi as concentric layers in accordance with the stages of the spermatogenic cycle. By means of PAS-reaction 18 stages have been revealed in spermatogenesis of the fur-seal and basing on the first 15 of them, 15 stages of the spermatogenic cycles have been presented. Transformations of the nucleus during the process of spermatids development proceed similar to other animals studied, formation of acrosomes is accompanied with a specific for the given species development of temporal formation--tubulo-bulbar complexes, reduced at terminal stages of spermiogenesis. PMID- 2222212 TI - [Tasks of the departments of operative surgery and topographic anatomy of medical schools in the light of the reorganization of higher education]. PMID- 2222213 TI - [Department of Histology and Embryology of the Kiev Medical Institute (on the 120th anniversary of its founding)]. PMID- 2222214 TI - [Chronic interstitial lung diseases. The status of the problem]. AB - Literature and original data on etiology, pathogenesis and morphogenesis of chronic nonspecific lung diseases provided the authors with evidence leading to conclusions on common pathogenesis of the above wide spectrum of the diseases characterized by affected intercellular relations in the lungs. Immunologic homeostasis is suggested as an essential factor resultant in the disease progression along the vicious circle in case of its defective functioning. PMID- 2222216 TI - [The pathological anatomy of secondary immunodeficiency]. AB - Secondary immunodeficiency is a polyetiological syndrome resulting mainly from the influence of exogenic factors and manifesting in the lack of immune response and nonspecific defence. Adequate documentation of secondary immunodeficiency revealing its role in the cause-result relationship when analysing the course of disease will improve not only evaluation of events but will create the conditions for the correction of secondary immunodeficiency the feasibility of which is proven experimentally. PMID- 2222215 TI - [Chronic inflammatory processes in the lungs: their intravital pathologicoanatomic diagnosis and prognosis]. AB - Combined morphological study of 714 bronchial biopsies and 363 samples of bronchoalveolar lavage (BAL) from 560 patients with chronic inflammatory diseases of nonspecific and tuberculous etiology was carried out. By light microscopic, electron microscopic and radioautographic investigation it was shown, that more important criteria of the dynamics of pathologic process, the stages of compensatory-adaptive reorganization of the lungs and the prognosis of disease were the structural-metabolic transformation of surface epithelium (metaplasia to stratified squamous epithelium or its atrophy) and the quantitative-qualitative characteristics of alveolar macrophages. A correlation was revealed between metabolic activity of BAL cells and those of bronchial epithelial cells, which determined the structural-functional interaction between the airways and respiratory part of the lungs under chronic inflammatory processes and promoted the right interpretation of clinical and morphological data. Morphological changes mainly of degenerative, but noninflammatory genesis often observed in the last years during chronic inflammatory processes in the lungs, are considered in terms of regenerative-plastic insufficiency of cells and intracellular structures. PMID- 2222217 TI - [Tumor growth and immunodeficiency states]. AB - The paper concerns problems of relations between tumor growth and immune system, complications of the tumor process due to immunodeficiencies and anticancer treatment, risk of metachronous tumors onset. Paraneoplastic phenomena and development of second tumors in patients treated in AUCRC are described. The pathologist should be active in carrying out a detailed clinical and anatomical analysis of malignant diseases. PMID- 2222218 TI - [Congenital immunodeficiency syndromes]. AB - The definition of the congenital immunodeficiency syndrome (CIDS) is given. Structural alterations of the thymus in combination with zonal disturbances and cell composition of the peripheral lymph organs are main morphological manifestations of CIDS. The most reasonable classification of CIDS is that based on etiology and thus making necessary to reconsider the existing terminology with an exclusion of such terms as "primary" and "secondary" immunodeficiency. The crucial point in the CIDS pathogenesis is a time of structural disturbances resulting from the action of an altering factor on the immune system in ontogenesis. A list of diseases of the histiomonocytic system is given which can be used as a basis for developing the classification of CIDS of the above system as the most ancient element in the immune response in the phylo- and ontogenesis. PMID- 2222219 TI - [The pathological anatomy of acute inflammatory lung diseases in adults]. AB - The paper relates the author's concern for diminishing interest of the pathologists to investigations of adult acute pneumonia, though chronic lung diseases and acute childhood pneumonia draw much attention. It is believed invalid to neglect classic methods of histobacterioscopy which are to be advanced. The researchers should insist on introduction of improved techniques of enzyme immunoassays in identification of pulmonary infection of viral and bacterial origin, study new kinds of pneumonias such as legionnaires' disease, Mycoplasma pneumonias, opportunistic infections in primary and secondary immunodeficiencies, e.g. AIDS, etc., presenting a wide field for the prosector's activity. PMID- 2222220 TI - [New data on thymomegaly as a syndrome of congenital (primary) immunodeficiency]. AB - Basing on a combined clinicomorphological investigation of the thymicolymphatic and neuroendocrine systems including measurements of blood thymic hormones and their levels in thymic tissue it is shown that congenital thymomegaly can be considered a dysfunction of the hypothalamo-hypophysial system. The dysfunction manifests with polyglandular endocrinopathy and congenital immunodeficiency related to the group of thymus-dependent immunodeficiencies. Thymomegaly is often coupled with congenital malformations. PMID- 2222222 TI - [The modelling of chronic infection (experimental leprosy) against a background of macrophagal immunodeficiency]. AB - The dynamics of mycobacterial multiplication was followed in mice with intraplantar leprosy infection and preinduced macrophage insufficiency. The characteristics of Shepard's model appeared to be similar to those of the method proposed by the authors including the susceptibility to the main antileprosy drugs. Peritoneal macrophages were cytochemically studied in the process of development of mononuclear phagocyte deficiency and experimental leprosy. It was concluded that the method proposed preserving all the merits of Shepard's model should allow one to shorten significantly the duration of testing potential drugs for their antileprosy activity. PMID- 2222221 TI - [Principles of the morphofunctional classification of granulocyte deficiencies]. AB - On the basis of qualitative and quantitative indexes of the plasmatic-cellular system of neutrophilic leukocyte /NL/ a classification of granulocytic deficiencies /GD/ is developed, 4 forms of GD are distinguished: agranulocytosis, granulocytasthenia, myeloproliferative conditions and inflammatory leukocytosis. As a clinicomorphological criterium of GD a triad is suggested that includes a tissue necrosis, microbism and inflammatory infiltration. Functional failure typical for every form of GD has it sown features. PMID- 2222223 TI - [The tasks of pathological anatomy (pathology) in the medical college and the possible means for their resolution]. AB - The course of pathologic anatomy in medical students' training is unsatisfactory as it doesn't cover many aspects of present-day human pathology. The graduates lack necessary knowledge in general and special pathology. The existing system of pathologist training is deficient, it should last for at least 4 years (subinternship, internship, clinical internship). Coordinated plans of advanced training of both the teachers and the pathologists are necessary. The relationships between chairs and bureaus of pathology should be systematized and creation of educational-scientific-practical complexes validated. PMID- 2222224 TI - [The most important prospects and tasks in improving the postgraduate instruction of pathologists under perestroika]. AB - It is suggested to reorganize the postgraduate training of pathologists by improving the technical basis of pathology chairs in accordance with modern achievements of medicine and state examinations requirements. The postgraduate training should be continuous and be realized by a self-education and pathologist participation in special courses and teaching cycles with subsequent qualification examination for the 2nd, 1st and highest category (after 5, 7 and 10 years, respectively). PMID- 2222225 TI - [Postgraduate instruction and certification in the system of the continuing education of pathologists]. AB - The experience in changing pathology service, postgraduate training and attestation in the system of continuous education of pathologists is presented. The authors analysed different ways of pathologist training: specialization in subinternship, internship and clinical internship, short-term courses, at places of work and outpatient problem seminars, etc. The four-year program of pathologist training is suggested. PMID- 2222226 TI - [The organization of the training of scientific and teaching personnel with high qualifications in connection with the approval by the Council of Ministers of the USSR of the Regulations on the procedure for awarding academic degrees and conferring academic titles of 30 December 1989]. PMID- 2222227 TI - [A case of malignant hemangiopericytoma of the pulmonary trunk valve of the heart]. AB - A description of one case: 62-year-old woman died during an operation for a tumour of the right lung. Malignant haemangiopericytoma of the pulmonary trunk valve was found at the necropsy with an occlusion of pulmonary trunk and metastasis to the right lung. PMID- 2222228 TI - [Apropos the article by G. G. Avtandilov et al. The professional qualification requirements for the clinical pathologist in a general hospital]. PMID- 2222229 TI - Australian midwives--politically active? What implications does this have for more effective policy making in health care? PMID- 2222230 TI - The Australian College of Midwives: a decade in review. PMID- 2222231 TI - The psychosocial-cultural aspects of pregnancy and holistic nursing care. AB - This paper discusses various psychosocial/cultural aspects of pregnancy that may alter the behaviour of the expectant couple. Holistic care plans are more likely to be effective if nurses are cognizant of these influences on the health of the child bearing couple. The quality of life from the moment of conception depends on a vast number of factors not the least being the physical and mental health of the expectant parents. Australian midwives contribute to the quality of maternal and fetal life by providing care throughout the pregnancy. In holistic care the health of the father is also considered therefore the quality of care provided to the growing family in the 1980's is a product of the nurses' knowledge. PMID- 2222232 TI - Women to have more say in births? PMID- 2222233 TI - "The alternative or the norm for the future?". PMID- 2222234 TI - Antihelminthic therapy for neurocysticercosis. PMID- 2222235 TI - No evidence for human T-cell leukemia virus type I or human T-cell leukemia virus type II infection in patients with multiple sclerosis. AB - The involvement of human T-cell leukemia viruses (HTLVs) in the pathogenesis of 18 Hungarian patients with multiple sclerosis was investigated. No antibody to HTLVs could be detected in any of the patients. Furthermore, using polymerase chain reaction under highly sensitive conditions, neither HTLV-I DNA nor HTLV-II DNA could be noted in peripheral blood lymphocytes of the patients. Our data do not support a causal association of HTLV-I or HTLV-II with multiple sclerosis. PMID- 2222236 TI - Failure to detect human T-cell leukemia virus-related sequences in multiple sclerosis blood. AB - We tested 11 patients with multiple sclerosis for the presence of human T-cell leukemia virus type I (HTLV-I)- or type II (HTLV-II)-related sequences. DNA from blood mononuclear cells was analyzed by the polymerase chain reaction utilizing three different oligonucleotide primer pairs. Two of these primer pairs detect sequences shared between HTLV-I and HTLV-II in either p24, gag protein, or in p21, env transmembrane protein. The third primer pair was synthesized based on regions in the pol gene where amino acid sequences are conserved between HTLV-I, HTLV-II, and the related bovine leukemia virus. The multiple sclerosis samples were consistently negative while appropriate control samples were positive. We conclude that viruses related to HTLV-I, HTLV-II, or bovine leukemia virus are not present in the blood of patients with multiple sclerosis and, therefore, that HTLV-bovine leukemia virus-related viruses are not likely to be involved in the pathogenesis of multiple sclerosis. PMID- 2222237 TI - Apneic oxygenation in apnea tests for brain death. A controlled trial. AB - We performed a prospective controlled study of apneic oxygenation on 15 patients undergoing apnea tests for brain death. All patients were preoxygenated with 100% oxygen at existing respirator settings. During the 10-minute apnea tests, nine patients were given continuous apneic oxygenation by tracheal cannula. The other six patients had tracheal tubes open to room air. The patients given apneic oxygenation had little or no hypoxia by the end of the test. The patients given room air during the test became hypoxic. Many neurologists perform apnea tests with no oxygenation or with preoxygenation alone. This is the first prospective controlled study (to our knowledge) of apneic oxygenation; it shows that preoxygenation alone does not prevent hypoxia during apnea tests for brain death. We recommend that all apnea tests be performed with apneic oxygenation. PMID- 2222238 TI - Geographic patterns of parkinsonism-dementia complex on Guam. 1956 through 1985. AB - Average annual age-adjusted incidence rates of parkinsonism-dementia complex were obtained for the 19 election districts of Guam from 1956 through 1985. The highest rates were found in the southern and central districts, and the lowest rates were found in the northern and western districts. Geographic and temporal patterns of incidence were associated with socioeconomic status but not with geochemical factors. The risk of parkinsonism-dementia complex in susceptible sibships was much higher than that in the general population--even in districts with the highest incidence rates, but especially in districts with the lowest incidence rates. Our evidence tends to support the hypothesis that multiple factors linked to cycad use play an important role in the cause of PDC. Hypotheses related to metal exposure and simple genetic factors were unsatisfactory explanations for the epidemiologic patterns observed. PMID- 2222239 TI - Racial differences in the anterior circulation in cerebrovascular disease. How much can be explained by risk factors? AB - The entry characteristics of 1367 patients enrolled into the Extracranial/Intracranial Bypass Study were examined to determine if site differences in intracranial and extracranial arterial lesions among racial groups could be explained by differences in risk factors. Blacks were more often hypertensive, diabetic, or cigarette smokers, while whites had higher systolic blood pressure and hemoglobin values. Orientals had the lowest prevalence of vascular risk factors. Despite these differences in risk factors, multivariate analysis showed race to be an independent and strong predictor of the location of cerebrovascular lesions. To our knowledge, this study is unique in documenting risk factors prospectively and systematically in three racial groups simultaneously. Although generalization is limited by possible biases related to patient selection, the results affirm previous tentative conclusions about the role of race in determining the location of cerebrovascular disease. PMID- 2222240 TI - The large striatocapsular infarct. A clinical and pathophysiological entity. AB - We examined 29 patients with strictly subcortical large striatocapsular infarctions. Eight of them had aphasia or neglect. All patients underwent transcranial Doppler ultrasonography or selective carotid angiography, magnetic resonance imaging, and single photon emission tomography for assessment of cerebral blood flow, blood volume, and cerebral perfusion reserve. The signs were compatible with cortical territorial infarctions rather than lacunes. On both magnetic resonance imaging and computed tomographic scans, the lesions corresponded to the territories of the medial and lateral group of the lenticulostriate arteries, Heubner's artery, or the anterior choroidal artery. The infarctions were either due to cerebral embolization into the M1 segment of the middle cerebral artery or due to stenosis at the same site, ie, lesions that acutely and simultaneously occluded the orifices of the lenticulostriate or neighboring arteries. Persistent occlusion of the middle cerebral arteries and a decrease of cortical regional cerebral blood flow were only found in patients with aphasia or neglect. All patients without aphasia or neglect showed a rapid recanalization of the middle cerebral artery occlusion or a stenosis of the M1 segment and no cortical regional cerebral blood flow decrease. Large striatocapsular infarctions occur due to occlusive disease of the middle cerebral artery (large-vessel disease) and not due to a disseminated in situ occlusion of the long penetrating arteries (small-vessel disease), as in lacunes. Neuropsychological deficits can be explained by decreased cortical blood flow due to a persistent occlusive lesion of the middle cerebral artery. PMID- 2222241 TI - Deep perforators from the carotid system. Template of the vascular territories. AB - Most reports on small infarcts in the territory of the deep perforators that arise from the internal carotid artery and its branches have focused on the anatomical structures. Recently, it has become possible to map the territories of the deep perforators from the carotid system, based on matching previous anatomical studies with recent data from computed tomographic and magnetic resonance imaging studies. The middle cerebral artery gives origin to two main groups of perforators: the medial and lateral lenticulostriate arteries. Rarely, the thalamotuberal artery may take origin from the middle cerebral artery but much more commonly it originates from the posterior communicating artery. The anterior cerebral artery gives origin to the anterior lenticulostriate arteries and the recurrent artery of Heubner. The anterior choroidal artery takes its origin from the internal carotid artery and exceptionally from the middle cerebral artery. In addition, a small group of perforators comes directly from the internal carotid artery. The anatomical structures supplied by these perforators are described, and a map of the territories is proposed. PMID- 2222242 TI - Failure of surgery to improve outcome in hypertensive putaminal hemorrhage. A prospective randomized trial. AB - Hypertensive putaminal hemorrhage remains a major cause of hemorrhagic stroke carrying extremely high morbidity. Considerable controversy remains regarding the optimal form of therapy. Between 1983 and 1989 we conducted a prospective randomized trial with three treatment strategies: best medical management, best medical management plus intracranial pressure monitoring, and surgical evacuation. Only patients with significant deficit harboring a putaminal hematoma at least 3.0 cm in diameter were entered. The study was interrupted after 21 patients had been studied (9, best medical management; 4, intracranial pressure monitoring; and 8, surgical evacuation). No differences were found among groups for age, admission blood pressure, and time interval between onset of symptoms and arrival at hospital. None of the subjects were capable of returning to prestroke activity. Fifteen (71%) died or remained vegetative at 6 months, and only 4 (19%) were capable of independent life at home. Of the 9 patients in the best medical management arm, 7 were dead or vegetative. In the surgical group, 4 patients died and only 2 were capable of independent life. These results suggest that current medical and neurosurgical therapies remain ineffective in preventing the devastating neurologic consequences of hypertensive putaminal hemorrhage. PMID- 2222243 TI - Brain imaging abnormalities in mental disorders of late life. AB - Psychiatric inpatients with dementia (N = 61) or depression (N = 67) in late life were 2.6 times more likely to manifest magnetic resonance imaging abnormalities of the brain than were elderly controls (N = 44). Controlling for the effects of age and gender, demented patients were distinguishable from controls by an increased prevalence of cortical atrophy and infarction, while depressed patients exhibited an increased prevalence of cortical infarctions and leukoencephalopathy. Patients with dementia were distinguishable from those with major depression by an increased prevalence of cortical atrophy. These results indicate that major depression in late life, like dementia, is associated with a remarkable increase in overt pathologic changes in the brain. PMID- 2222245 TI - X-linked spinal muscular atrophy (Kennedy's syndrome). A kindred with hypobetalipoproteinemia. AB - Kennedy's syndrome, X-linked adult-onset bulbospinal muscular atrophy, has been described in over 30 families. The characteristic distribution of weakness creates a recognizable syndrome, augmented by frequent findings of testicular atrophy and gynecomastia. Type IV or type II hyperlipoproteinemia has been found in some families. We have studied another family with Kennedy's syndrome, this one with hypobetalipoproteinemia. The diversity of serum patterns suggests that lipoprotein abnormalities are not causally related to either the endocrinopathy or the spinal muscular atrophy. However, gene linkage studies indicate proximity of the gene for Kennedy's syndrome and the gene encoding the androgen receptor, which could explain the combination of a motor neuron disorder and the endocrine abnormalities. PMID- 2222244 TI - Adjuvant chemotherapy for primary lymphoma of the central nervous system. AB - Ten immunocompetent patients with primary non-Hodgkin's lymphoma of the central nervous system were treated by the neuro-oncology service at the University of California at San Francisco (UCSF). After undergoing surgery for biopsy or removal of their tumors, these patients (group 1) received irradiation with hydroxyurea followed by adjuvant chemotherapy with the combination of procarbazine, lomustine (CCNU), and vincristine. The outcome of treatment in this group was compared with that in three other groups of patients with primary CNS lymphoma: patients treated at the UCSF Cancer Research Institute who underwent surgery and radiation therapy (RT) (group 2); patients described in the literature who had surgery and RT (group 3); or patients described in the literature who had surgery, RT, and chemotherapy (group 4). Median and quartile survival times were greater in patients who received adjuvant chemotherapy (group 1, 30 and 50 months; group 4, 20 and 25 months) than in patients who did not receive chemotherapy after RT (group 2, 13 and 20 months; group 3, 15 and 24 months). These results suggest that adjuvant chemotherapy is useful in the treatment of primary CNS lymphoma. PMID- 2222246 TI - GM-1 treatment of Alzheimer's disease. A pilot study of safety and efficacy. AB - A double-blind, placebo-controlled pilot study was conducted to evaluate the safety and efficacy of treatment of patients with Alzheimer's disease using monosialoganglioside GM-1, a neurotrophic factor. Of 46 patients enrolled, 42 completed all study requirements. Nineteen patients received 100 mg of GM-1 by daily intramuscular injection for 12 weeks. Twenty-three patients received placebo. Case evaluations were done at baseline, week 12, and week 24 and included both cognitive and psychosocial scales. Study results suggested that the treatment was safe, yet offered no overall symptomatic benefit to patients with mild-to-moderate Alzheimer's disease. Whether or not GM-1 therapy may offer protective benefit by slowing or arresting the progression of the disease remains unclear, since the results of the cognitive evaluations suggested that neither the GM-1 group nor the placebo group declined significantly during the 24-week study. PMID- 2222248 TI - Low-grade gliomas: to treat or not to treat? A radiation oncologist's viewpoint. PMID- 2222247 TI - Episodic hyperammonemia in adult siblings with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. AB - A 39-year-old man and his 42-year-old sister, both vegetarians, had episodic confusion for many years, but their mental function was normal between those episodes. They were recently diagnosed with hyperornithinemia, hyperammonemia, and homocitrullinuria syndrome. Hyperammonemia was documented during an episode of confusion in the male sibling but not in his sister. Both had elevated plasma ornithine, glutamine, and alanine levels and persistently low plasma lysine levels. Homocitrulline was present in their urine, and orotic aciduria and orotidinuria developed in the male sibling following ingestion of allopurinol. Studies on their cultured skin fibroblasts showed deficient metabolism of ornithine, indicating a defect in ornithine transport across the mitochondrial membrane. During therapy with citrulline and phenylbutyrate sodium, plasma ornithine levels increased in both patients, while plasma levels of glutamine and alanine decreased to normal. Since therapy started, their clinical conditions have also improved, and no recurrent neurologic dysfunction has occurred during a follow-up period of 20 months. PMID- 2222249 TI - Congenital myopathy and cardiomyopathy with identical ultrastructural changes. AB - A 7-day-old girl with congenital hypotonia and unexplained episodes of bradycardia had a broad spectrum of similar skeletal muscle and myocardial degenerative ultrastructural abnormalities. Ultrastructural studies showed obliteration of cross striations, myofilament disorganization, streaming, smearing, clumping, and zigzag Z-band deformities. A decrease in glycogen, mitochondria, and T-tubular system occurred in the regions showing Z-band abnormalities of both skeletal muscle and myocardium. Concurrent structural cardiomyopathy should be considered in patients with congenital myopathies, particularly with unexplained cardiac conduction abnormalities or contractile insufficiency. Ultrastructural evaluation of skeletal and cardiac muscle may be necessary to define such disorders. PMID- 2222250 TI - Unusual cause of 'piriformis muscle syndrome'. AB - The piriformis muscle syndrome is a controversial "clinical" syndrome primarily characterized by signs and symptoms of sciatic nerve compression at the region of the piriformis muscle as it passes through the greater sciatic notch. The syndrome is often referred to; however, cases are rarely reported, and it is generally an uncommon diagnosis. Of those cases reported, the incidence is six times more frequent in females than in males, and is typically temporally related to minor pelvic or buttock trauma. We describe a case of a 40-year-old woman presenting with signs and symptoms suggestive of piriformis muscle syndrome following a gynecologic procedure performed in the dorsal lithotomy position. Electromyographic findings were consistent with this clinical entity. Operative exploration, however, revealed the source of neural compression to be a pseudoaneurysm of the inferior gluteal artery adjacent to the piriformis muscle. The diagnostic features of this clinical syndrome are discussed. PMID- 2222252 TI - The induction of reparative dentine in the amputated dental pulp of the dog by bone morphogenetic protein. AB - Reparative dentine was formed in the cavity of the amputated pulp when capped with crude allogeneic BMP. This began with a slight cell-mediated immune response and was followed by resorption of BMP and proliferation of migratory spindle shaped mesenchymal cells, together with vascular invasion. Four weeks postoperatively, there were osteodentinoblasts embedded in forming matrix and/or osteodentinocytes trapped within osteodentine in some parts of the cavity. Other parts were filled with pulpal tissue. Eight weeks postoperatively, odontoblasts were forming tubular dentine next to the osteodentine. In albumin-implanted controls, a little osteodentine and no tubular dentine were seen. These findings suggest that dissolved BMP stimulates mitosis of mesenchymal cells and may induce differentiation of osteodentinocytes. The resultant osteodentine may play some role in the differentiation of odontoblasts. PMID- 2222251 TI - A new assessment in vitro of human salivary lubrication using a compliant substrate. AB - The lubrication effect of salivary secretions was assessed in terms of separating a rigid object from a compliant substrate. There was little difference among the various secretions of a single donor. The viscosity of salivas increased as a function of time. Neither the friction testing nor viscometry provided an adequate model of the tissue-coating function ascribed to saliva. PMID- 2222253 TI - A morphometric, electron microscopic analysis of tissue channels shown by ionic tracer in normal and tensioned rat molar apical periodontal ligament. AB - A 1.0 newton continuous, extrusive load was applied to the right maxillary molar for 30 min to determine the presence of channels as shown by the distribution of tracer across the interstitial compartment of normal and tensioned PDL. Sodium ferrocyanide (1% w/v), perfused via the common carotid arteries, was the tracer probe and tris(ethylenediamine) cobalt III chloride (1% w/v) the precipitating ion. Left molar control PDL had an overall mean of 0.43 +/- 0.05/microns2 tissue channels at 0.2 microns from the vascular endothelium, and 0.15 +/- 0.04/microns2 at 7-8 microns. On the experimental side, the overall mean number of tissue channels was 0.65 +/- 0.13/microns2 at 0-2 microns and 0.19 +/- 0.07/microns2 at 7-8 microns. A significant depth effect (P less than 0.01) was present in the control and experimental interstitial tissues for tissue channels adjacent to the endothelium of different categories of vessel. Extrusion increased the tissue channel density adjacent to arterial capillaries (P less than 0.01), venous capillaries (P less than 0.01) and postcapillary-sized venules (P less than 0.01). These findings implicate these three types of vessel as being functionally important in fluid exchange across endothelial boundaries in the PDL. PMID- 2222254 TI - The effects of a liquid diet on initial and sustained, stimulated parotid salivary secretion and on parotid structure in the rat. AB - Adult male rats were maintained on a nutritionally adequate liquid diet, or laboratory chow and water (controls), for 7 days. They were then anaesthetized and parotid flow was recorded after isoprenaline or pilocarpine stimulation, each collected over two, timed sampling periods--an initial 5 min and a subsequent 15 min. The isoprenaline-induced flow rates in liquid diet rats were reduced to 45 and 30% of those in control rats for the first and subsequent samples respectively (p less than 0.02). After pilocarpine stimulation there were no significant differences in the first samples, but in the subsequent samples the flow rate in liquid diet rats was reduced to 54% of that in controls (p less than 0.001). The parotid gland weights were reduced by 35% in liquid diet rats compared to controls (p less than 0.05). On computerized planimetric analysis, parotids (from rats that had not been given secretagogues) had significantly smaller mean acinar areas, mean acinar profile perimeters and mean acinar transection diameters after liquid feeding (p less than 0.001). The findings support the notion that there is a functional reserve capacity available in atrophied glands to support the relatively fast flow that occurs on initial stimulation but which becomes exhausted during sustained stimulation. This exhaustion occurs more severely and more rapidly in the low-volume, protein-rich saliva elicited by sympathomimetic stimulation than in the high-volume, low protein saliva formed in response to parasympathomimetic stimulation. PMID- 2222255 TI - Evaporative water loss from human dentine in vitro. AB - The rate of spontaneous evaporation of water from dentine was measured in extracted human teeth in vitro. Spontaneous water loss was the same with or without a smear layer. When air was blown on the dentine, the rate of evaporation increased significantly. After removal of the smear layer, the air blast-induced evaporative loss was twice as great as before its removal. Thus, with a smear layer present, evaporation is the major route by which fluid is lost from dentine rather than by filtration of dentinal fluid. After smear layer removal, fluid filtration sometimes may exceed the spontaneous rate of fluid evaporation. PMID- 2222256 TI - Gingival crevicular fluid prostaglandins and gingival phospholipids in experimentally-induced periodontitis in the dog. AB - Prostaglandins are known to be mediators of inflammation in many tissues. Their fluctuations in gingival crevicular fluid during experimentally induced periodontitis were investigated, together with the possible role of phospholipids, which were measured in normal gingiva and gingiva associated with the chronic periodontitis. Periodontitis was induced in 5 dogs in the lower premolar quadrant; the opposite quadrant was used as a control. A small amount of inter-radicular bone was removed and then a cotton-wrapped stainless steel ligature was placed around each of 3 premolar teeth below the gingival margin to provide an inflammatory irritant. Pocket depth was measured by periodontal probe; crevicular fluid was collected on absorbent paper points. PGs were analysed by HPLC and the results expressed as ng PG/microliter crevicular fluid. Measurements were taken in both quadrants at 1, 3 and 6 weeks after placement of the ligatures; PGI2, 6 keto-F1 alpha, F2 alpha, E2, E1 and D2 were detected in the crevicular fluid. At 1 week, there was no difference in PG levels between experimental and control sides. During week 3, PGI2 and PGE2 increased in the experimental crevicular fluid [214.1 +/- 49.3 (SEM) vs control 87.0 +/- 39.7; p less than 0.05 and 350.0 +/- 115 vs 162.0 +/- 14.7; p less than 0.05, respectively]. At week 6, only PGE2 was elevated in crevicular fluid (207.7 +/- 68.1 vs 99.2 +/- 45; p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222257 TI - Computer-assisted estimation of lines of action of human masticatory muscles reconstructed in vivo by means of magnetic resonance imaging of parallel sections. AB - The orientation of these lines of action was estimated in 9 healthy subjects, by reconstructing the muscle shape from a series of parallel sections obtained by MRI. In order to gain insight into sources of error, the lines of action of the masseter and medial pterygoid were estimated from two mutually perpendicular series of sectional images. Average results were compared with anatomical data from the literature. The results indicated that the accuracy of the estimate was principally dependent on the reliability of the reconstructions; the average accuracy of the estimated orientations was about 5 degrees. PMID- 2222258 TI - A quantitative method for assessing changes in rat palatal histology under denture-like appliances. PMID- 2222259 TI - Langerhans cells in human chronic gingivitis and phenytoin-induced gingival hyperplasia. AB - Langerhans cell numbers in oral epithelium increase as dental plaque accumulates. The anti-convulsant drug phenytoin predisposes to gingival hyperplasia in certain patients who take this medication for epilepsy and who also have poor oral hygiene. In this study 7 patients with phenytoin-induced gingival hyperplasia were compared with 5 subjects with chronic marginal gingivitis. On initial examination and on completion of the hygiene phase of periodontal therapy (a period ranging from 3.0 to 4.25 months), clinical indices of plaque and gingivitis were recorded and biopsies were taken from the lower anterior labial gingiva. Frozen sections were stained by an immunoperoxidase technique using the monoclonal antibody OKT6, and the number of Langerhans cells in a defined cross sectional area was counted. In phenytoin-induced gingival hyperplasia there was a marked increase in Langerhans cells (13.8 +/- 0.45) when compared with chronic gingivitis (7.7 +/- 0.31; p less than 0.05). Both groups showed marked reductions in their plaque and gingival indices and numbers of Langerhans cells once treatment had been completed. However, levels of Langerhans cells in the drug induced hyperplasia remained significantly higher (3.5 +/- 0.26) than in chronic gingivitis (1.5 +/- 0.22; p less than 0.05). PMID- 2222260 TI - Expression of fibronectin and type I collagen by human dental pulp cells and gingiva fibroblasts grown on fibronectin substrate. AB - Specific antibodies and indirect immunoperoxidase labelling were used to study the intracellular production of collagen and fibronectin by cells grown on fibronectin-coated glass; the same cell populations seeded on uncoated glass were used as controls. Strong intracellular staining for type I collagen was seen in all cases, but immunostaining for fibronectin was very faint or negative in both gingival and pulp cells grown on the fibronectin substrate, in contrast to control cells. Thus, fibronectin substrate inhibited fibronectin synthesis by the cultured cells, but did not seem to influence type I collagen synthesis. PMID- 2222261 TI - Binding of salivary or serum proteins to Candida albicans in vitro. AB - This binding was investigated with a simplified method: whole saliva and mucin bound to C. albicans in significantly greater quantities than other proteins such as whole serum, albumin, lysozyme or fibrinogen; and the enzymatic treatment of C. albicans with chymotrypsin, papain or mannosidase decreased the amounts of these proteins bound. These results, taken together, suggest that salivary proteins or mucin may bind to the mannoprotein of C. albicans. PMID- 2222262 TI - Cryotherapy for retinopathy of prematurity: none, one, or both eyes. PMID- 2222263 TI - The choice of posterior chamber intraocular lens style in patients with diabetic retinopathy. PMID- 2222264 TI - Blindness and visual impairment in an American urban population. PMID- 2222265 TI - Blacks at greater risk for blindness. PMID- 2222266 TI - Teaching ophthalmology in medical schools. PMID- 2222267 TI - Too much eye surgery? PMID- 2222268 TI - A yellow-green posterior limbal ring in a patient who does not have Wilson's disease. PMID- 2222269 TI - Generalized giant-cell arteritis with coronary artery involvement and myocardial infarction. PMID- 2222270 TI - Band keratopathy from emulsified silicone oil. PMID- 2222271 TI - Federal agency to develop cataract management guidelines by January 1991. PMID- 2222272 TI - Do we have a nutritional treatment for age-related cataract or macular degeneration? PMID- 2222273 TI - The molecular genetics of Leber's hereditary optic neuropathy. PMID- 2222274 TI - Multicenter trial of cryotherapy for retinopathy of prematurity. One-year outcome -structure and function. Cryotherapy for Retinopathy of Prematurity Cooperative Group. AB - This study of the safety and efficacy of cryotherapy in treating severe retinopathy of prematurity registered 9751 infants with birth weights less than 1251 g at 23 study centers. Two hundred ninety-one infants developed a defined threshold retinopathy of prematurity, and cryotherapy was performed in approximately half of the eyes through a randomization protocol. Twelve months after randomization, results of masked grading of fundus photographs of the posterior pole were similar to results obtained 3 months after randomization, and indicated an unfavorable outcome in 25.7% of the eyes that received cryotherapy compared with 47.4% of the control eyes (P less than .0001). For the first time, masked Teller Acuity Card assessment of grating acuity was performed in this study group and indicated an unfavorable functional outcome in 35.0% of the treated eyes compared with 56.3% of the control eyes (P less than .0001). These results indicate that cryotherapy reduces the risk of unfavorable retinal and functional outcome from threshold retinopathy of prematurity. PMID- 2222275 TI - Echographic features of the Vogt-Koyanagi-Harada syndrome. AB - Vogt-Koyanagi-Harada (VKH) syndrome represents a spectrum of bilateral panuveitis with associated central nervous system and dermatologic manifestations. The diagnosis is based on clinical and angiographic findings, but some of the characteristic features may be either absent or difficult to visualize in the presence of opaque media. With the use of standardized echography (standardized A scan and contact B-scan echography), we examined nine patients with clear media and clinical evidence of VKH syndrome. Consistent echographic findings included (1) diffuse, low to medium reflective thickening of the choroid posteriorly; (2) serous retinal detachment, located inferiorly or in the posterior pole; (3) mild vitreous opacities with no posterior vitreous detachment; and (4) thickening of the sclera and/or episclera posteriorly. Resolution of these findings occurred with systemic corticosteroid therapy. Standardized echography should be considered an important diagnostic tool in VKH syndrome, especially when visualization of the fundus is poor or when clinical presentation is atypical. PMID- 2222276 TI - Clinical and morphometric results of penetrating keratoplasty with one-piece anterior-chamber or suture-fixated posterior-chamber lenses in the absence of lens capsule. AB - The clinical records and serial corneal endothelial images of 25 acapsular, pseudophakic eyes with Kelman-style, one-piece, anterior-chamber intraocular lenses and 24 acapsular, pseudophakic eyes with suture-fixated, posterior-chamber intraocular lenses following penetrating keratoplasty were reviewed to determine clinical success and endothelial survival after 1 year. Twenty-two (88%) of 25 grafts in the anterior-chamber intraocular lens group and 23 (96%) of 24 grafts in the sutured posterior-chamber intraocular lens group were clear after 1 year; best corrected visual acuity of 20/40 or better was noted in 25% of the eyes in the anterior-chamber intraocular lens group and 29% of the eyes in the sutured posterior-chamber intraocular lens group. The mean intraocular pressure for the anterior-chamber intraocular lens group was significantly lower than for the sutured posterior-chamber intraocular lens group at 3 months (17 +/- 4 vs 21 +/- 7 mm Hg) and at 6 months (17 +/- 3 vs 20 +/- 5 mm Hg); but did not differ at 1 year. The mean percent of endothelial cell loss after 1 year did not differ between the anterior-chamber intraocular lens group (32% +/- 26%) and the sutured posterior-chamber intraocular lens group (27% +/- 26%). No clinical or endothelial morphometric advantages were noted after 1 year for the suture fixated, posterior-chamber intraocular lens over the Kelman-style, one-piece anterior chamber, intraocular lens following pseudophakic penetrating keratoplasty; however, a long-term, prospective, randomized study of these two intraocular lens types is recommended. PMID- 2222277 TI - Botulinum vs adjustable suture surgery in the treatment of horizontal misalignment in adult patients lacking fusion. AB - Thirty patients were treated with either botulinum toxin or adjustable suture surgery in a prospective, randomized clinical trial. All patients had horizontal deviations greater than 10 prism diopters and absent fusion. Seventeen patients were assigned to toxin treatment, and 13 were assigned to surgical treatment. Follow-up at 6 months after either procedure indicated that surgery was superior, with patient alignment showing a 92.7% average net change, compared with a 50.50% net change in the botulinum-treated group. There was no difference in response between those patients with a starting deviation of 20 PD or less and greater than 20 PD in the surgery group. However, in the botulinum-treated group, those patients with a starting deviation of 20 PD or less seemed to show better responses than those patients with greater than 20 PD. Patients with esotropia showed an 88.89% change with surgery and a 51.55% change with toxin treatment. Patients with exotropia had a 95.83% change with surgery but a 50.3% change with toxin treatment. Since we had 20 patients with exotropia and 10 patients with esotropia, a more formal comparison would require larger numbers. PMID- 2222278 TI - Assessment of vitamin A status by a disk applicator for conjunctival impression cytology. AB - Conjunctival impression cytology was performed on 236 Indonesian preschool children, half of whom had mild xerophthalmia and half of whom were age-matched controls. We devised an applicator that applies a paper disk of fixed area to the conjunctiva with even pressure. The disk applicator was used to collect impression cytology specimens from the temporal bulbar conjunctiva of one eye while the original strip technique was used on the other eye. Mean (+/- SD) serum retinol values for children with normal and abnormal discs were 22.0 +/- 8.6 micrograms/dL and 18.0 +/- 7.2 micrograms/dL P less than .0001). Mean serum values for normal and abnormal strips were 21.7 +/- 8.6 micrograms/dL and 19.0 +/ 7.7 micrograms/dL (P less than .03). Specimens obtained with the new disk applicator corresponded more closely with serum vitamin A levels and therefore vitamin A status than those obtained with the traditional strip technique. PMID- 2222279 TI - A comparison of wound healing in sutured and unsutured corneal wounds. AB - We compared corneal wound healing in 25 clear transplants with 26 keratotomy specimens and sutured and unsutured corneal wounds in a monkey model. Monkey wounds healed faster than human wounds, but healing time within the same species varied. Sutured wounds were characterized by subepithelial fibroplasia, recovery of collagen fiber continuity and absence of epithelial plugs. Unsutured wounds had no subepithelial fibroplasia but had fibroblasts and collagen fiber orientation parallel to wounds. Unsutured wounds in corneas containing sutures had subepithelial fibroplasia, and fibroblast orientation and fiber deposition parallel to the wound. Epithelial ingrowth and incarceration of Bowman's layer and/or Descemet's membrane in unsutured wounds appeared to disrupt wound healing. Abnormalities in wound healing in sutured or unsutured wounds are associated with lamellar distortion, a modified inflammatory response, and individual wound healing responses. PMID- 2222280 TI - S-antigen. Identification of human T-cell lymphocyte proliferation sites. AB - Immune responses to normal retinal proteins, including S-antigen, have been demonstrated in patients with a variety of retinal disorders, as well as in those who have received panretinal laser photocoagulation. T-cell lymphocytes (T cells) have been implicated in the pathogenesis of several ocular inflammatory diseases of possible autoimmune etiology. We used synthetic peptides that correspond to the amino acid sequence of S-antigen in lymphocyte proliferation assays to identify specific sites in the molecule recognized by human T cells. Ten patients with type II diabetes were studied before and after initial panretinal laser photocoagulation for proliferative diabetic retinopathy. T-cell responses, expressed as a stimulation index, to S-antigen and peptides were negative in all patients before treatment. Three weeks after panretinal laser photocoagulation, eight of 10 assays were positive (stimulation index greater than 2; P less than .01) when lymphocytes were stimulated with peptide BSA(273-292); six of nine were positive (P less than .01) with peptide BSA(303-332); and six of six were positive (P less than .001) with peptide BSA(343-362). Our study identifies several specific sites in S-antigen that elicit human immune responses. The implications of these findings with regard to the pathogenesis and treatment of autoimmune uveitis are discussed. PMID- 2222281 TI - Recurrent Acanthamoeba keratitis following penetrating keratoplasty. PMID- 2222282 TI - A two-stage technique for intraoperative fluid-gas exchange following pars plana vitrectomy. AB - We describe herein a two-stage technique of intraoperative fluid-gas exchange following pars plana vitrectomy. The first stage is a complete fluid-air exchange using an air pump and intraocular linear suction. The air pump then maintains the intraocular pressure at the desired level during adjunctive procedures, such as laser endophotocoagulation. The second stage is an air-gas mixture exchange in which the desired gas, premixed in air to the desired final intraocular concentration, is manually flushed through the eye. This technique allows the attainment of an accurate concentration of intraocular gas if the air-gas mixture exchange is complete. In vitro and in vivo experiments in aphakic human eyes demonstrated that an effectively complete air-gas mixture exchange occurs with a 25-mL flush volume. This result compares favorably with the theoretical prediction derived from a "pharmacokinetic approximation" equation. PMID- 2222283 TI - [Relationship between years of methamphetamine use and symptoms of methamphetamine psychosis]. AB - The authors researched the demographic characteristics of 233 patients with methamphetamine-associated disorders, and the relation between years of methamphetamine use and symptoms of methamphetamine psychosis. The results were as follows: There were more male users than females. However there were signs that the female users were gradually increasing. Users tended to be older, but users in their 20's and 30's continued to be predominant. Their school careers were usually limited and most of them had left school at a young age. Relations with a particular social group (e.g. organized gangs) has given most of them a chance to use methamphetamine. The symptoms that were seen with high frequency at the first examination were anxiety, fretfulness, auditory hallucination, insomnia, irritability, psychomotor excitement, delusion of persecution, suspicion, delusion of reference, mistake of circumstance, loss of appetite, affective disorder, hypobulia and personality change. With these symptoms, there is a possibility that five years of methamphetamine use is the turning point in terms of the frequency of symptoms occurrence. It was suggested that affective and perceptual disorders depend on the dose of methamphetamine, but abnormalities in thought subject may be deeply influenced by the patient's "feeling of social wrong". Emotional exhilaration and euphoria decreased as the number of years of methamphetamine use increased. These phenomena may be an indication of tolerance. The symptoms that were seen with high frequency at the last examination were hypobulia, affective disorder, personality change, insomnia, anxiety and fretfulness. The symptoms that were highly resistant to treatment were hypobulia, affective disorder, personality change, general malaise, hypochondriasis, insomnia, anxiety and fretfulness. It was suggested that five years of methamphetamine use may be a turning point in the residual rate of symptoms at the last examination after treatment, and also the resistance rate to treatment. Hypobulia and personality change became more evident during treatment. PMID- 2222284 TI - [Study of the antibody to alcohol altered hepatocyte plasma membrane in alcoholic patients]. AB - Significance of the antibody to alcohol altered hepatocyte plasma membrane (AAHM) was studied in various types of alcoholic liver diseases (ALD). AAHM was detected in the sera that were collected within 3 months of alcohol abstinence from patients with various types of ALD, with higher frequency in alcoholic hepatitis and cirrhosis. Serum acetaldehyde, gamma-globulin fraction, immunoglobulin A and G were higher in patients positive for AAHM, though the levels of GOT, GPT, mGOT were indifferent of the existence of AAHM. Histologically, hepatocyte ballooning and pericellular fibrosis were frequently seen in patients positive for AAHM, but close relationship between the extent of necrosis and existence of AAHM was not observed. These findings suggest that the occurrence of AAHM is closely related with the functional and morphological changes of the hepatocyte induced by acetaldehyde but not with hepatocyte necrosis. PMID- 2222286 TI - [The use of Pugh score to evaluate the prognostic and therapeutic influence of drinking in patients with decompensated liver cirrhosis]. AB - The aim of this study is to evaluate the clinical usefulness of Pugh score in the prognosis of the patients (pts.) with decompensated liver cirrhosis (DLC). To determine the influence of heavy drinking with respect to the prognosis of DLC patients, 128 cases of DLC were divided into two groups including the 31 heavy drinker group (Group A) and 97 non-alcoholic group (Group B). At the time of admission, the both groups showed similar Pugh score. However, after initial two hospitalized weeks, Group A started to show significantly lower points of Pugh score than that of in Group B. Fifteen pts. (48%) in Group A and 55 pts. (57%) in Group B had greater than 9 in Pugh score at the time of admission. In Group A, 10 of 15 pts. declined the scores after initial two weeks and 9 of them lived more than one year after admission. In contrast, none of those 55 pts. in Group B declined their Pugh score after admission and 45 of them died within one year. It was concluded that Pugh score was extremely useful to evaluate the prognosis of DLC pts., and DLC pts. who had greater than 9 Pugh score were seemed to be critical. It was suggested that DLC pts. due to heavy drinking tend to improve Pugh score comparing to no alcoholic DLC pts. PMID- 2222285 TI - [Influence of alcohol ingestion on plasma gastrin and CCK levels in human beings]. AB - We investigated the time courses of the plasma ethanol, acetaldehyde, gastrin and cholecystokinin (CCK) levels after the ingestion of ethanol (1g/kg, 21.5%, whisky) in healthy male adult volunteers. The ethanol level reached a peak at 15 to 45 minutes after the ingestion and then decreased almost linearly. The acetaldehyde level of the group who became flushed after drinking (the F group) peaked earlier than that of the other group whose faces became only slightly flushed (the N group). The gastrin level increased significantly and remained elevated for about 3 hours. In three of the nine subjects, the CCK level increased 75 minutes after drinking. As a result, the absorption of the ingested ethanol is more rapid than 15 minutes, followed by a quick catabolism of the absorbed ethanol to acetaldehyde, but the catabolic action of acetaldehyde in the F group is later than that in the N group. The plasma gastrin level is certified to increase after the ingestion of ethanol and this is not mediated by acetaldehyde because the intra-venous infusion of acetaldehyde was not increased the plasma gastrin level in dogs. CCK which stimulate the pancreatic enzymes may be considered to have a possibility relating to the development of alcoholic acute pancreatitis but the ingestion of ethanol showed no increase of the plasma CCK level. But we cannot deny the possibility of the individual differences in the hormonal reaction in these experiments. PMID- 2222287 TI - Frequency specificity of the auditory brainstem response elicited by 1,000-Hz filtered clicks. AB - In normal-hearing subjects and in subjects with a flat cochlear hearing loss, auditory brainstem responses (ABR) were recorded at various levels of a 1,000-Hz filtered click stimulus with and without high-pass filtered masking noise. The difference in latency of the major peak in the ABR for the masked and unmasked condition was zero at the ABR threshold. We regard this as proof of the frequency specificity of the 1,000-Hz filtered click-stimulated ABR threshold. The difference between ABR threshold and the subjective puretone threshold at 1,000 Hz amounted to 19 dB in normal-hearing subjects and to 10 dB in subjects with a flat cochlear hearing loss. This is probably related to loss of temporal integration and an abnormal loudness growth (recruitment). PMID- 2222288 TI - Influence of menopause on the auditory brainstem response. AB - Auditory brainstem response (ABR) wave latency, interpeak interval and amplitude as a function of intensity were measured in 40 subjects divided into equal groups of postmenopausal females, age-matched males and young adults of both sexes. The results illustrate that age and gender play a significant role in ABR wave latency and amplitude. A larger age effect occurred for the female subjects. While this does not dispute an anatomical explanation for the gender effect in ABR, hormonal changes accompanying menopause may also account for some of the gender differences noted in ABR. PMID- 2222289 TI - Evoked-response tone-on-tone masking in the chinchilla: effect of masker frequency. AB - Tone-on-tone masking patterns were measured at 0.5, 1, and 4 kHz using the auditory-evoked response from the inferior colliculus of the chinchilla. Masking profiles obtained with a masking level of 30 dB SPL were relatively symmetrical; however, as masker level increased, masking spread toward the high frequencies, particularly with the 0.5-kHz masker. For masker frequencies of 1 and 4 kHz, a low-threshold notch was observed in the masking profile 2/3 of an octave above the frequency of the masker. The low-threshold notch may represent a response to the distortion tone 2F1-F2. The notch was absent in the 0.5-kHz masking profile. The masking profiles obtained with the evoked response are somewhat wider, but otherwise qualitatively similar to those measured psychophysically in humans. Thus, the evoked-response procedure may provide a convenient way of evaluating the spread of masking and the presence of distortion tones in difficult-to-test subjects. PMID- 2222290 TI - Auditory steady-state responses in the rabbit. AB - The authors have studied auditory brainstem (ABRs), middle latency (MLRs) and steady-state potentials (SSRs) in 15 adult male rabbits weighing between 2.5 and 3 kg in order to verify if SSRs are due to a mere superimposition of ABRs and MLRs or to a resonance phenomenon. Ten of them were awake while 5 were studied under urethane anesthesia. Acoustic stimuli consisted in 0.1-ms square-wave pulses delivered at presentation rates ranging between 1 and 80/s at a stimulus intensity of 80 dB p.e. SPL. Our data show that reliable auditory SSRs can be obtained in the rabbit at a presentation rate of 30 stimuli/s, probably due to the superimposition of ABRs and MLR Pb waves which show an interwave interval of about 35 ms. The nonlinear aspects which can be detected are probably due to the effect of decreasing interstimulus intervals on the duration and amplitude of the Pb wave. It can then be concluded that SSRs in the rabbit are due more to a superimposition of ABR and MLR waves than to a resonance phenomenon. PMID- 2222291 TI - Effect of sound-absorbing treatment on speech discrimination in rooms. AB - Noise and reverberation in a room affect speech discrimination. Sound-absorbing materials are used to shorten reverberation times. To find out the effect of acoustic treatment on speech discrimination, an acoustic refitting was carried out in a classroom and in a multipurpose hall. The normal-hearing test subjects perceived the word material (sentences, words and nonsense words) binaurally from the loudspeaker. The tests were repeated after the acoustic refitting of the rooms. The sound-absorbing treatment improved speech discrimination. In quiet, the improvement in discrimination was minimal or absent, but was well documented in a noisy environment. In rooms where speech communication takes place, attention should be paid to acoustic conditions: acoustic treatment can improve the quality of communication. PMID- 2222292 TI - Procedure learning effects in speech perception tests. AB - The effects of procedure learning were studied using data obtained from normal hearing subjects by presenting words under noise either in isolation or in the context of sentences. The data establish firmly an effect of procedure learning on the performance of subjects during a 1-hour testing session when the subjects have participated in a previous 1-hour testing session during which about 250 test words were presented. The magnitude of the effect is equivalent to a shift in signal-to-noise ratio of the order of 1 dB. PMID- 2222294 TI - Unstable angina pectoris. AB - In recent years, there have been considerable advances in our understanding of the complex pathophysiology of unstable angina. A number of therapeutic options are now available. This article reviews current concepts of pathophysiology and summarises clinical features, natural history and available treatments. PMID- 2222293 TI - Aspirin and thrombolytic therapy in the management of acute myocardial infarction. AB - The use of aspirin and thrombolytic agents in the management of acute myocardial infarction is now accepted as standard clinical practice, but not all patients with heart attack are suitable for such therapy. This article provides practical guidelines for patient management and the background information on which these recommendations are based. PMID- 2222295 TI - Update on percutaneous transluminal coronary angioplasty and CABG. AB - Over the past decade percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) have undergone substantial changes. The growth of PTCA has been phenomenal and it now accounts for about 50 per cent of revascularisation procedures at Royal Perth Hospital. Coronary surgery has undergone less growth, but it is now being successfully used in a much more elderly and high risk group of patients without an increase in mortality. PMID- 2222296 TI - Cardiac rehabilitation. The human face of heart disease. AB - Cardiac patients have a number of physical, psychological and social problems. With adequate rehabilitation, most patients can return to all their normal activities and lead enjoyable, productive lives. PMID- 2222297 TI - Cardiac failure. Current therapeutic concepts. AB - Reflection on basic mechanisms in cardiac failure gives an insight into the modes of therapy available in management. Therapeutic options have in the past two decades expanded markedly with enhanced quality and quantity of life. With end stage disease the option of a heart transplant is providing quality of life to increasing numbers of selected patients. PMID- 2222298 TI - Permanent cardiac pacemakers. Indications and current trends. AB - In Australia, most patients requiring permanent cardiac pacing have either high grade atrioventricular block or sick sinus syndrome. Many receive simple ventricular demand pacemakers, but more 'physiological' systems are now available that allow changes in pacing rate depending on metabolic needs. The indications for pacemakers and the types available are discussed in this article. PMID- 2222300 TI - Simple tests for carpal tunnel syndrome. PMID- 2222299 TI - Valvular heart disease. Part I: Diagnosis. AB - Cardiac murmurs are common. The general practitioner is often the first person to detect a murmur. These are often asymptomatic, yet may be a consequence of haemodynamically significant valve disease. Accurate assessment is important to allow intervention and to improve prognosis. The clinical features of each valve lesion and relevant cardiac investigations are discussed. PMID- 2222301 TI - Perceptions of the FRACGP examination. A study of Victorian candidates. AB - It is proposed that by 1995 Fellowship of the Royal Australian College of General Practitioners will be the only recognised endpoint of vocational training in general practice in Australia. Currently however only one in six eligible general practitioners and one in three college members holds the FRACGP in Victoria. This case-controlled study carried out by survey questionnaire was designed to compare and contrast perceptions of the FRACGP examination of a group of candidates with a group of demographically matched non candidates. The study suggested that those who sat the examination did so to improve their self esteem, and wished their knowledge, competence and skills to be 'peer reviewed'. PMID- 2222302 TI - Acute sore throat. AB - The second common problem to be presented in this series is the acute sore throat. The common causes are viral pharyngitis and tonsillitis due to streptococcus pyogenes. Another important cause that warrants attention is Epstein Barr virus (infectious mononucleosis) so that prescribing of penicillins is carefully considered. The sore throat may be the presentation of serious and hidden systemic diseases, such as blood dyscrasias, AIDS and diabetes (due to moniliasis). PMID- 2222304 TI - Penetrating gun injuries. PMID- 2222303 TI - James Montague Bonwick, OBE. Fifty six years a country doctor. PMID- 2222305 TI - Chest pain of unusual cause. PMID- 2222306 TI - Patient education. Your stuffy, running nose. PMID- 2222307 TI - Do you believe in miracles? PMID- 2222309 TI - Solving the problems of country practice. PMID- 2222308 TI - Cardiovascular risk factors. PMID- 2222311 TI - Panic and phobic disorders. Current cognitive behavioural strategies. AB - The past 5 years have seen the development of a number of treatment strategies suitable for panic and phobic disorders. At this stage, a combined drug and psychological approach is appropriate. Not all patients will accept medication. A number of cognitive-behavioural techniques can be used with hope of success. Sessions must include positive statements such as 'you can do it', 'be persistent', 'look forward to this activity' and 'I am achieving'. PMID- 2222310 TI - Current treatment concepts in depression. AB - Depression is a common disorder. While depressive symptoms are often transient and may be regarded as normal, 10 per cent of the population suffers depressive symptoms of sufficient severity and duration to be diagnosed as suffering a depressive illness. PMID- 2222312 TI - Depression in the elderly. AB - Depression in the elderly is an eminently treatable disease. It may masquerade as a pseudo dementia--a reversible condition with proper treatment. The need for an eclectic approach to management is emphasised and the special needs of the elderly outlined. PMID- 2222313 TI - Depression in children. AB - Unhappiness and transient feelings of depression are common normal experiences for many children. Persistent depressive illness occurs in about 2 per cent of children and seriously affects social, educational and emotional development. Treatment usually requires family therapy and behavioural and psychotherapeutic measures. Antidepressant medication has an occasional role in cases with a biological basis. PMID- 2222314 TI - Hospital and general practice co-operative initiatives in education. AB - All these developments demonstrate what can be achieved by the presence, within the teaching hospital system, of a person who is recognised as being responsible for general practice training. Considerable progress has been made, but it is emphasised that this has been an evolutionary process. Further, almost all the programmes and activities that have evolved have been built on ideas initiated by the Director of Ambulatory Paediatrics or were already in the minds of a number of people but not implemented because of other commitments. The co-ordinator has been in a position to adopt these ideas and put them into practice. PMID- 2222315 TI - The management of ingrown toenails. AB - Ingrown toenail is an unpleasant condition often affecting young people. Surgery is often necessary for its treatment. A simple office procedure is described, with details and special precautions, which results in few complications and generally a good outcome. PMID- 2222316 TI - The painful arm. AB - The painful arm often presents a diagnostic challenge. The cause is often obvious, especially with regional pain syndromes including the carpal tunnel and the tennis elbows. However, pain reference syndromes can be confusing and it is advisable to first examine the cervical spine because it is a common and often overlooked cause of arm pain or paraesthesia. It is common for arm pain to cause sleep disturbances and in such cases it is worth considering cervical causes, carpal tunnel syndrome and the thoracic outlet syndromes. The working rule is: patients with thoracic outlet syndrome cannot fall asleep; a carpal tunnel lesion wakes the patient in the middle of the night; and cervical spondylosis wakes the patient with pain and stiffness that persists well into the day. PMID- 2222317 TI - Diagnosis of patellofemoral pain syndrome. AB - This syndrome, also known as chondromalacia patellae, is characterised by pain and crepitus around the patella during activities that require flexion of the knee under loading, for example, climbing stairs. PMID- 2222318 TI - Patient education. Contraception while breastfeeding. AB - Practising an effective form of contraception while breastfeeding can do much to ease your mind and allow you to enjoy life more. There are many 'old wives' tales' about breastfeeding and contraception. PMID- 2222319 TI - Notable Australian doctors. Dr Cyril Checchi, country doctor. PMID- 2222320 TI - Infectious diseases. Report from ASID, 1990. PMID- 2222322 TI - Spatula sketches for kids. PMID- 2222321 TI - A Yankee bug in Oz. PMID- 2222323 TI - 'Sacked'. PMID- 2222324 TI - Storing polio vaccine. PMID- 2222325 TI - Twin registry. PMID- 2222327 TI - A query on rebates. PMID- 2222326 TI - Any tips for dealing with consulting room flashers? PMID- 2222328 TI - Patients and empowerment. PMID- 2222329 TI - The role of the RACGP. PMID- 2222331 TI - Long-term effects of intense sound on hair cells of Corti's organ and endocochlear DC potential. AB - Cochleograms of guinea pig ears were made 30-40 days after exposure to intense pure tones of 300 Hz, 500 Hz, 2 kHz, or 4 kHz at 130-150 dB SPL for 4-24 h. At 4 kHz, hair cells in the basal turn disappeared totally, in the second turn moderately, and were relatively undamaged in the third and apical turns. At 500 Hz, hair cells in the second and third turns were almost completely injured and at 300 Hz moderately damaged in the third and apical turns although the basal turn remained undamaged. At 2 kHz for 9 h, hair cells were almost completely injured in all turns. Negative endocochlear DC potential (negative EP) induced by furosemide was observed in the basal turn but not in the third turn of animals exposed to 300 Hz. Contrarily, negative EP was observed in the third turn but not in the basal turn of animals exposed to 4 kHz. We conclude that the hair cells of Corti's organ play an essential role in the production of negative EP. PMID- 2222330 TI - Laryngeal epithelial changes on effects of smoking and drinking. AB - The human larynx is essential not only for speech, but also for swallowing and respiration. Its tissues are affected by the presence of alcohol and cigarette smoke. In this report we present our findings on the effects of smoking and drinking on histological changes in laryngeal tissue. The larynges studied were those of autopsy patients: cases with damaged tissue were excluded. We studied the larynges of 84 men (non-smoker and non-drinker, 22 cases; smoker and drinker, 62 cases) and 48 women (non-smoker and non-drinker, 40 cases; smoker and drinker, 8 cases) between the ages of 12 and 88. The squamous metaplasia of laryngeal epithelium was examined using the gross staining method (Pyronin Y) of STELL et al. (J. Laryngeal. Otol. 86: 589-594, 1972). The squamous epithelium is unstained, whereas the respiratory epithelium is a brilliant red. The area of metaplasia in the supraglottic region increased with aging, tobacco and alcohol consumption. Microscopic changes of the laryngeal epithelium were investigated using the hematoxylin-eosin staining method. The thickness of epithelium of the supraglottic region and vocal cord increased with age. There is a significant difference in the thickness of the epithelium of the supraglottic region and vocal cords of smoking and drinking patients, when compared with the same tissues of non-smokers and non-drinkers. Furthermore, there is a significant difference in those tissues of the supraglottic region of heavy smokers, when compared with light smokers, but no significant difference when compared with drinkers. However, there is no significant difference in the thickness of vocal cord tissues when comparing light smokers and drinkers on the one hand, and heavy smokers and drinkers on the other. PMID- 2222332 TI - Autonomic indexes during the vestibular-visual conflict exposure: a squirrel monkey study. AB - To assess the dynamic changes of the autonomic neural responses evoked by vestibular-visual conflict (VVC) in the squirrel monkey, we analyzed the changes of salivary amount and sodium concentration, and the coefficient of variance (CV) of R-R intervals (RRI) along the time course of VVC exposure given in pitch plane. The sodium concentration and the amount of saliva showed clear increases at the first and second 15 min stimulation periods. The CV of RRI was found to increase over the entire periods of stimulation, and there was a significant difference between the rest value and those in stimulated periods. The correlation between the CV of RRI, and amount of salivation was highly positive. These results indicate the existence of a common pattern of autonomic neural response during VVC, and suggest usefulness of these indexes for objectively monitoring the severity of motion sickness. PMID- 2222334 TI - Sinus histiocytosis with massive lymphadenopathy in a Japanese male with symptoms of dyspnea and visual disturbance. AB - A case study of sinus histiocytosis with massive lymphadenopathy is reported. A Japanese male developed lymphadenopathy in the nasal cavity 10 years ago. Biopsy specimens demonstrated massive histiocytosis with phagocytosis of lymphocytes, plasmacytes, and erythrocytes. During the course of his illness, the patient experienced an episode of massive nasal bleeding, and a tracheotomy was performed because of dyspnea. He had also an operation by Killian's approach to relieve a visual disturbance. The patient has been treated with cyclophosphamide and prednisolone for 6 months. PMID- 2222333 TI - Cryosurgery of the inferior nasal turbinates. AB - Forty-seven patients with irreversible nasal obstruction due to inferior turbinate hypertrophy were treated by cryosurgery, the short and medium term results having been clinically evaluated. Permanent good results in nasal breathing were achieved in 83% of the patients. Failures are mostly related to turbinates hypertrophy due to nasal allergy. The combination of cryosurgery and nasal septoplasty, in cases of hypertrophy associated with deformities of nasal septum, gives an excellent result. Cryosurgery of hypertrophic nasal turbinates is a simple, safe, and reliable procedure to improve nasal breathing in cases of nasal turbinate hypertrophy. PMID- 2222335 TI - Maybe the patient has PTA? PMID- 2222336 TI - Dust, flies and my PC. PMID- 2222337 TI - Breast self-examination. A teaching role for nurses. PMID- 2222338 TI - Monitoring life. PMID- 2222339 TI - Member services under review. PMID- 2222340 TI - Towards a national nurse registering authority. PMID- 2222341 TI - Cardiac scare. PMID- 2222342 TI - Healthy alliances. PMID- 2222343 TI - The third age. Sexuality and sensuality. PMID- 2222345 TI - Are the safety limits safe? PMID- 2222344 TI - Drug delivery systems--oral and buccal. PMID- 2222346 TI - Fixing anomalies. PMID- 2222347 TI - Effect of eicosapentaenoic acid on restenosis rate, clinical course and blood lipids in patients after percutaneous transluminal coronary angioplasty. AB - In order to study the effects of eicosapentaenoic acid (Maxepa), Maxepa placebo and aspirin/dipyridamole combination on the clinical course and restenosis rate of atherosclerotic lesions after percutaneous transluminal coronary angioplasty 79 men and 29 women were randomly divided into three treatment groups and restudied angiographically within one year of the procedure. Angina recurred less in the Maxepa group than in the other groups, although not statistically so. Restenosis rate was significantly reduced in the Maxepa group (11%) compared to the placebo group (30%) but, while less, was not significantly lower than in the aspirin/dipyridamole group (17%). Maxepa treatment appears to reduce restenosis rate of coronary artery lesions after percutaneous transluminal coronary angioplasty and may be an acceptable and equally effective alternative therapy to aspirin/dipyridamole. PMID- 2222348 TI - Length of hospital stay after acute myocardial infarction. AB - A number of trials show that long stay in hospital after an acute myocardial infarction (AMI) is not necessary for many patients and that stays of three-ten days may be adequate. All patients aged under 70 years with a diagnosis of AMI admitted to the seven public hospitals in the Lower Hunter Region of New South Wales are monitored as part of the WHO MONICA Study. Between August 1984 and December 1985 of 438 hospitalised patients with a 'definite' AMI according to MONICA criteria and a clinical discharge diagnosis of AMI, 386 (88%) patients were discharged alive from hospital. Four patients had lengths of stay between 46 and 77 days and have been omitted from further analysis. The mean length of hospital stay was 13.6 days (95% confidence intervals 12.9 to 14.3 days); 74% of all patients stayed in hospital for more than ten days. The mean length of stay in the Coronary Care Unit (CCU) was 4.5 days (95% confidence intervals 4.2 to 4.8 days) with 60% staying longer than three days. Mean hospital stay varied from 10.5 to 17.4 days among the seven hospitals, although most of this variation was accounted for by three hospitals with few patients. Restricting analysis to the four hospitals with 90% of all the patients, multiple regression analysis showed that the CK enzyme levels, the evolution of Q waves on ECG, the presence of an anterior AMI and the use of nitrates and digoxin during hospitalisation were all associated with increased length of stay in hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222349 TI - Does the emergency room electrocardiogram identify patients with suspected myocardial infarction who are at low risk of acute complications? AB - To determine the early morbidity of patients admitted to the coronary care unit (CCU) with inconclusive evidence of acute myocardial infarction, the prognostic value of the emergency room electrocardiogram (ECG) was examined prospectively in a blinded fashion in 410 patients presenting with acute chest pain. One hundred and forty one patients (34.4%) had an ECG that was normal, showed ST segment changes less than 1 mm, or was unchanged from a previous recording (group 1). The remaining patients (65.6%, group 2) had ECGs considered abnormal. Thirty-nine patients in group 1 and 226 in group 2 had confirmed infarction. There was one CCU death in group 1 (0.7%) versus 27 (10.0%) in group 2 (p less than 0.001) and the overall hospital mortality for group 1 was 2.1% versus 13.0% in group 2 (p less than 0.001). Twenty-eight patients (19.9%) from group 1 suffered complications in the CCU versus 155 (57.6%) from group 2 (p less than 0.001). No life-threatening arrhythmias occurred in group 1 versus occurrence in 47 patients (17.5%) in group 2 (p less than 0.001). The need for acute intervention was also less for group 1 versus group 2 patients, 14 (9.9%) and 85 (31.6%) respectively (p less than 0.001) with no patient requiring electrical cardioversion in group 1. It is concluded that the emergency room ECG can reliably identify a group of low risk patients presenting with suspected myocardial infarction and so help in establishing priority for admission to the CCU. Furthermore, the risk-benefit of thrombolytic therapy in these low risk patients appears unacceptable. PMID- 2222350 TI - The effect of ageing on autonomic nervous system function. AB - We studied 76 healthy subjects (five-85 years) with a number of invasive and non invasive tests of autonomic function. Age related effects were found with the tests of predominantly vagal cardiovascular function. However, there were no age related effects found with the tests of predominantly sympathetic cardiovascular function. The age of the subject should be taken into consideration when evaluating tests of autonomic function and each laboratory should establish its own control values. PMID- 2222351 TI - Lack of airway response to nasal irritation in normal and asthmatic subjects. AB - Twenty two subjects (10 normals, nine asthmatics and three who had suggestive histories for asthma but normal bronchial histamine challenges) underwent nasal challenges with logarithmic incremental doses of histamine or saline on alternate days. Nasal resistance (measured by posterior rhinometry), and forced expiratory volume in one second (FEV1) were assessed after each dose of nasal histamine or placebo. After each nasal challenge (maximum nasal dose of 250 micrograms of histamine or doubling of nasal resistance) bronchial responsiveness was measured with a bronchial histamine challenge. Despite significant changes in nasal resistance with nasal histamine (p less than 0.01) there was no significant change in the forced expiratory volume in one second, or in bronchial responsiveness. We were unable to demonstrate nasobronchial reflexes initiated by acute irritation of the nasal mucosa with histamine in either normal subjects or in those with mild to moderate asthma. PMID- 2222352 TI - The influence of dialect group on peptic ulcer frequency amongst the Chinese in Singapore. AB - In Singapore, peptic ulcer is more common amongst Chinese than amongst Malays or Indians. Earlier work has suggested that, amongst female Chinese, Cantonese women are more susceptible to ulcer disease when compared to females of other dialect groups. The aim of the present study was to confirm or refute this possibility. The dialect group distribution of 897 Chinese patients with peptic ulcer (duodenal ulcer 601, gastric ulcer 296) was compared with that of non-ulcer dyspepsia patients and 1602 general medical patients attending the same medical units. The proportion of various dialect groups (including Cantonese) was similar in all patient groups. The proportion of ulcer patients presenting with haemorrhage was also similar in the different dialect groups. We conclude that no major dialect differences exist in peptic ulcer frequency amongst the Chinese in Singapore. PMID- 2222353 TI - An unusual case of variegate porphyria with possible homozygous inheritance. AB - We report an unusual case of variegate porphyria in a young girl with epilepsy, mental retardation and premature adrenarche. Symptoms of porphyria commenced about the age of 12 years and death occurred about 18 months later. The patient had very low protoporphyrinogen oxidase activity in her cultured fibroblasts. Both parents had half the normal activity of this enzyme in lymphocytes and are heterozygous for the abnormal gene for variegate porphyria. Therefore, it is possible that the patient was a homozygous variant. Anticonvulsant therapy and low hepatic 5 alpha reductase activity were probably other contributing factors to the severity of the condition in this patient. PMID- 2222354 TI - Pituitary apoplexy presenting as aseptic meningitis without visual loss or ophthalmoplegia. AB - Clinical and spinal fluid evidence of aseptic meningitis were the sole features at presentation in a patient with pituitary apoplexy. Visual impairment and bitemporal field defects developed later. Necrosis within a chromophobe adenoma was found at surgical decompression of the sella. PMID- 2222355 TI - Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin. AB - A forty-year-old female presented with an unsteady gait 13 years after receiving an eight-month course of human pituitary-derived gonadotrophin injections as treatment for infertility. Over the next ten months the patient subsequently developed generalised myoclonic jerks and dementia and finally died. Neuropathological examination revealed changes in the brain consistent with Creutzfeldt-Jakob disease. This is the first reported case of Creutzfeldt-Jakob disease in a recipient of human derived gonadotrophin. PMID- 2222356 TI - Cardiovascular reflexes from cardiac sensory receptors. AB - The mammalian heart, especially its left ventricle, is densely innervated by sensory nerves. One set of these travels to the brainstem in the vagus nerves; the other to the spinal cord in sympathetic nerves. Excitation of vagal cardiac afferents, especially unmyelinated afferents from the left ventricle, cause a reflex bradycardia and fall in blood pressure and, under some conditions, a massive release of AVP. The sympathetic afferents convey the sensation of cardiac pain, but innocuous stimuli may cause a reflex tachycardia and rise in blood pressure. Both sympathetic and vagal cardiac afferents can be excited by mechanical distension of the heart (mechanoreceptors), and by a variety of foreign and endogenous chemical substances (chemosensitive receptors). It is not yet clear whether the effective natural stimulus to these receptors is mechanical, or through the chemical products of myocardial metabolism. Neither is it clear whether information from the heart exerts a minute-to-minute regulatory effect on the circulation, or whether it has a purely defensive role in the face of extreme disturbances of cardiac function. Cardiogenic reflexes are also thought to be the cause of haemodynamic and humoral disturbances that occur in clinical conditions such as myocardial ischaemia or infarction, left ventricular outflow obstruction, and acute reduction in central blood volume as well as during coronary angiography. PMID- 2222357 TI - Electrocardiographic identification of late potentials: a new noninvasive technique for identifying patients with ventricular tachycardia. PMID- 2222358 TI - Disseminated histoplasmosis in an AIDS patient. PMID- 2222359 TI - Neurological features of early and latent HIV. PMID- 2222360 TI - Cardiogenic brain embolism: role of anticoagulants. PMID- 2222361 TI - Permanent infertility in ewes exposed to plant oestrogens. AB - In Australia, more than 1 million ewes have permanently damaged reproductive tracts because they have been grazed on oestrogenic pasture. These effects occur in the absence of classical clinical "clover disease". The lesions result from an "organisational" action of oestrogen, causing a mild sexual transdifferentiation to occur in ewes during adult life, with the main lesion being found in the cervix. Diagnosis of the problem depends primarily on detection of the pathological changes, rather than history or clinical signs. On average, affected flocks have around a 10% increase in non-pregnant ewes, but most farmers can achieve an acceptable lambing rate by increasing their management and feed inputs to produce more twin lambs. Agronomic approaches have been used in the past to combat "clover disease", but further progress with the present problem may depend on the development of animal-based solutions. PMID- 2222362 TI - Streptococcus suis serotypes associated with disease in weaned pigs. AB - Streptococcus suis was recovered from 9 outbreaks of septicaemia and meningitis in weaned pigs between 1979 and 1983. Fifteen isolates from 7 outbreaks were identified as S. suis type 9, and 3 isolates from 2 outbreaks as S. suis type 2. Three further isolates of S. suis type 2 and an isolate of S. suis type 3 were recovered from cases of bronchopneumonia in weaned pigs from 4 other piggeries. PMID- 2222363 TI - Effects of zeranol implants on post-castration response in calves. AB - Suckling and yearling calves were surgically castrated and one half of each group implanted with 36 mg zeranol at time of castration. Both treated and control cattle of each class were maintained as a group and evaluated for swelling of the scrotum, inflammation and healing, plasma prostaglandin levels and weight gain. Swelling and inflammation of the scrotum were less in treated suckling calves than in controls at both 7 and 14 d after castration, though this difference was not statistically significant. In yearlings at 7 d after castration, treated cattle had more swelling than controls; however at 14 d, treated cattle had less swelling and inflammation with only one treated yearling having an open scrotal wound versus 6 (P less than .03) in the control group. Plasma prostaglandin levels as indicated by plasma malondialdehyde increased from d 0 to 14; however no significant treatment differences were observed for either age group. Suckling calves treated with zeranol gained 9.79 kg more (P less than .03) than non treated calves during the 97 d of trial while the yearlings treated with zeranol gained 16.78 kg more (P less than .01) than controls during 102 d. It is concluded from the increased growth and reduced scrotal swelling and inflammation in treated cattle that zeranol implantation could possibly have a beneficial effect in improving the healing process after castration. PMID- 2222364 TI - Yersiniosis in farmed deer. AB - Samples from 77 chital (Axis axis), 42 fallow (Dama dama), 26 red (Cervus elaphus), 7 rusa (Cervus timorensis) and 1 sambar deer (Cervus unicolor) were examined. Yersinia pseudotuberculosis infection was diagnosed as the cause of death in 6 (23%) of the red and 23 (30%) of the chital deer. Yersiniosis was the most common infectious cause of death diagnosed. Affected deer were usually found moribund or dead, often with faecal staining of the perineum. Gross pathology in chital included a fibrinous enterocolitis, enlarged congested mesenteric lymph nodes and multiple pale foci through the liver. Gross changes in red deer were limited to intense congestion of the intestinal mucosa and enlargement and congestion of mesenteric lymph nodes. Microscopic intestinal changes in both species consisted of microabscessation or diffuse suppurative inflammation of the intestinal mucosa with numerous bacterial colonies in the lamina propria. Multifocal suppurative mesenteric lymphadenitis was a common finding. Multifocal suppurative or non-suppurative hepatitis was frequently present in the liver of chital but was uncommon in the red deer. Yersiniosis occurred during the cooler months from June to November, with younger age classes most commonly affected. Y. pseudotuberculosis serotypes I, II and III were isolated in the ratio 17:3:0 in the chital deer and 1:1:2 in red deer. The clinical, epidemiological and bacteriological features are similar to those documented previously by New Zealand workers. The increased susceptibility to disease of red deer and chital compared to fallow deer and perhaps other species has not previously been documented. PMID- 2222365 TI - Thiamine deficiency in sheep exported live by sea. AB - Three shipments of sheep being exported live by sea were examined to determine their thiamine status. Measurements were made of thiamine concentration in liver and ruminal contents, transketolase activity in erythrocytes and thiaminase activity in ruminal liquor. Sheep that died or were clinically ill and euthanased had significantly lower hepatic and ruminal thiamine concentrations than clinically healthy control sheep. A high proportion had thiamine concentrations comparable to those found in sheep that die with polioencephalomalacia. Thiamine concentrations decreased with increasing time that sheep were in pre-embarkation feedlots and on board ship. Destruction of thiamine in the rumen by thiaminase was not a significant factor. Erythrocyte transketolase activities indicated that many of the sheep that arrived in the Middle East without signs of clinical disease were also in a state of thiamine insufficiency. PMID- 2222366 TI - Premature farrowings caused by feeding cottonseed meal. AB - Increasing the level of cottonseed meal (CSM) in sow diets from less than 5% to 10% increased the incidence of premature farrowings (gestation length less than 111 days) from 1.1% to 2.7% (p less than 0.001) and reduced the mean gestation length from 114.07 +/- 1.53 to 113.70 +/- 1.59 days (p less than 0.0001). Survival of piglets born prematurely was poor. After removal of CSM from the diet there was a residual effect lasting several weeks before the gestation length returned to normal. Experimental feeding of diets containing 20% and 40% CSM to small groups of sows caused significant shortening of gestation length and 3 of 26 sows fed 40% CSM farrowed prematurely. The mechanism by which CSM causes this effect has yet to be determined. PMID- 2222368 TI - Kikuyu poisoning in goats and sheep. PMID- 2222367 TI - Cysticercus bovis in cattle in New South Wales. PMID- 2222369 TI - Treating lupin stubbles with alkali is unlikely to prevent lupinosis. PMID- 2222370 TI - Serum agglutinating antibodies to Leptospira interrogans serovar canicola presumed due to serovar robinsoni infection in an Australian dog. PMID- 2222371 TI - Resistance to Toxoplasma abortion in female goats previously exposed to Toxoplasma infection. PMID- 2222372 TI - Triclabendazole in the treatment of Fasciola gigantica infection in swamp buffalo (Bubalus bubalis). PMID- 2222373 TI - The sterility and productivity of young, short scrotum, merino rams. PMID- 2222375 TI - Genital pathology of feral male goats. AB - Genitalia from 1000 feral male goats derived from western Queensland and New South Wales were examined after slaughter at an abattoir and the prevalence of abnormalities determined. Ulcerative balanoposthitis, considered due to caprine herpesvirus infection, was observed in 11 animals (1.1%); acidophilic intranuclear inclusions were found in 7 of these. Other conditions included focal hypoplasia of seminiferous tubules in 2 bucks (0.2%), segmental aplasia of the epididymis (one buck, 0.1%), bulbourethral gland cysts with contained aggregations (33 bucks, 3.3%) and haemangiosarcoma of the bulbourethral gland in one animal. The low prevalence of several conditions such as spermatic granuloma, cryptorchidism, and testicular hypoplasia, was attributed largely to the fact that the bucks examined were horned so that the recognised association between genital abnormalities and polledness did not apply. PMID- 2222374 TI - The reproductive performance of farmed fallow deer (Dama dama) in New South Wales. AB - Observations on the reproductive performance of fallow deer on 47 farms in New South Wales were made over 6 consecutive years. The minimum fawning rate for does varied significantly (p less than 0.001) between years, the corresponding fawning percentages varying from 75.0% to 96.4%, with an overall mean of 88.8%. The weaning rate also varied significantly (p less than 0.001) between years, the corresponding percentages varying from 65.0% to 89.1% with a mean over 6 years of 81.4%. Weaning rates were low given the known high fertility of fallow deer. The ratio of male to female fawns at weaning varied significantly (p less than 0.05) between years, although the ratio was exactly 1:1 for all births recorded over the 6-year period. The mean birthweights for female and male fawns were 4.01 kg +/- 0.61 (n = 330) and 4.23 kg +/- 0.72 (n = 348) respectively. Mean birthweights varied significantly (p less than 0.001) between the sexes and between years. There was a greater difference between birthweights of male and female fawns in years with higher mean fawn birthweight. Fawn birthweights generally approximated 10% of the pre-rut weight of their mother. Handling of newborn fawns for tagging and weighting did not increase the chance of mismothering and rejection. The mean weaning weight for doe fawns and buck fawns over 6 years was 18.7 kg (n = 227) and 21.2 kg (n = 231) respectively, with a mean birth to weaning interval of 108.4 +/- 4.89 (n = 458). Growth rates of male fawns from birth to weaning were significantly higher (p less than 0.01) than for female fawns, and the growth rates of fawns were significantly different (p less than 0.01) between years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222376 TI - Vitamin A concentrations in commercial foods for dogs and cats. AB - The vitamin A concentration was determined in 89 Australian brands of commercial foods for dogs and cats. It was found that 8% of the dog foods and 14% of the cat foods had concentrations of vitamin A below the minimum recommended 1.1 mg/kg dry matter (dm) for dogs and 1.8 mg/kg dm for pregnant or lactating cats. Canned and fish-labelled cat foods were the only varieties with less than the minimum recommended concentration of Vitamin A, of which 71% were the same brand. The minimum recommended concentration of vitamin A was exceeded in all canned dog food tested. Concentrations of vitamin A in dry (ca. 6% moisture) dog and cat foods and semi-moist dog foods (ca. 23% moisture) never exceeded 10 mg vitamin A/kg dm. In contrast, canned pet foods stated to contain liver or kidney showed vitamin A concentrations from 13 to 284 mg/kg dm. PMID- 2222378 TI - Melioidosis in a koala. PMID- 2222377 TI - Evaluation of protection against experimental salmonellosis in sheep immunised with 1 or 2 doses of live aromatic-dependent Salmonella typhimurium. AB - The minimum number of doses of a live aromatic dependent (aro-) Salmonella typhimurium vaccine strain (SL1479), given by the intramuscular, oral or subcutaneous route required to protect sheep from experimentally-induced clinical salmonellosis, was determined. A significant reduction in mortalities and diarrhoea occurred in those sheep immunised with one or 2 intramuscular doses or 2 subcutaneous doses. On the other hand, sheep immunised with one subcutaneous dose were not protected. Immunisation with one or 2 oral doses also resulted in a significant reduction in mortality, although reduction in the prevalence of severe diarrhoea was less consistent. Sheep immunised with a single intramuscular dose of aro- S. typhimurium developed high levels of serum antibodies and significant delayed-type cutaneous hypersensitivity response to homologous Salmonella lipopolysaccharide and flagellin, whereas those with a single oral dose did not. It was concluded that immunisation of sheep with a single oral or intramuscular dose of live aro- S. typhimurium reduced mortalities and the prevalence of diarrhoea in sheep due to infection with virulent S. typhimurium. PMID- 2222379 TI - Use of a dietary supplement in koalas during systemic antibiotic treatment of chlamydial infection. PMID- 2222380 TI - Electrocardiographic values of German shepherd dogs. PMID- 2222381 TI - Mortality in calves associated with the feeding of milk containing bronopol. PMID- 2222383 TI - Parvovirus B19. A workshop organized by the German Association against Virus Diseases. April 1989. PMID- 2222382 TI - Trapping sheep blowflies using bait-bins. PMID- 2222384 TI - Molecular approaches for production of B19 antigen. AB - Owing to the lack of a practical means of production of large quantities of virus in cell culture, present tests to screen for parvovirus antibody rely on the use of virus obtained from the sera of blood donors during the brief, intensely viraemic phase of acute infection (Cohen et al, 1983). Accordingly, antigen is scarce and testing for parvovirus antibody is confined to a few centres. Availability of recombinant antigen would make the test more widely available, and by circumventing the requirement for use of whole virus render the test safer (Cohen et al, 1988). Therefore, constructs of parvovirus DNA encompassing the region of the genome coding for the structural proteins in expression vectors with T7 or trc or tac promoters were made, and proteins produced by the resulting clones tested for their ability to react with B19 antibodies from human sera. Additionally, recombinant B19 DNA was used as a hybridization probe for virus in clinical specimens, and a sensitive polymerase chain reaction assay was investigated as a tool for parvovirus diagnosis. PMID- 2222385 TI - The influence of family support on chronic pain. AB - This study examined the role family support plays in insulating chronic pain patients from maladaptive behaviors associated with their pain. Two hundred and thirty-three patients who described their family as always being supportive and never having any conflicts were compared with 275 chronic pain patients who endorsed having family disharmony and limited support. One year after completing an out-patient pain program a random sample of 181 of these patients were followed to determine the extent to which family support influenced treatment outcome. The patients who reported having non-supportive families tended to have liability and work-related injuries, relied on medication, reported having more pain sites and used more pain descriptors in describing their pain. These patients also tended to show more pain behaviors and more emotional distress compared with pain patients coming from supportive families. On follow-up, patients who described their families as being supportive reported significantly less pain intensity, less reliance on medication and greater activity levels. They tended to be working and not to have gone elsewhere for treatment of their pain compared with patients who described their family as non-supportive. The results of this study demonstrate that perceived support is an important factor in the rehabilitation of chronic pain patients. PMID- 2222386 TI - Types and correlates of blood/injury-related vasovagal syncope. AB - This study investigated by interview, the initial syncopal episode of 103 blood/injury-related vasovagal fainters in order to examine two competing hypotheses concerning their origins. Graham (Circulation, 23, 901-906, 1961) postulated that the faint resulted when sympathetic nervous system (SNS) activity ceased on termination of a threat, leaving parasympathetic nervous system (PNS) activation unopposed. Engel [Fainting (2nd edn), 1962; Annals of Internal Medicine, 89, 901-906, 1978] proposed that when in the face of threat with SNS activation, escape is blocked, the PNS becomes activated as the conservation withdrawal response, leading to syncope. We found cases clearly conforming to each of these formulations as well as some with characteristics of both, and some who fainted in response to blood or injury but with no perception of threat. The Graham and Engel types did not differ in terms of fear or avoidance of blood, injury, or medically-related situations nor did they differ in the frequency with which their parents reported blood/injury-related syncopal episodes. It is proposed that both may be activated by a common psychological mechanism involving cessation of a defensive posture. In contrast, the non-threat fainters showed significantly less medically-related avoidance and had a greater percentage (94%) of parents with positive faint histories. PMID- 2222387 TI - The relationship of appraisal and coping to chronic illness adjustment. AB - There is evidence that adaptation to chronic illness may be affected by psychological factors, especially how patients appraise and cope with the stress of their illness. The purpose of the present study was to examine the relationship of stress appraisal and coping responses to multiple behavioral indices of illness adjustment among patients with diverse chronic medical conditions. One hundred and one patients admitted to a multidisciplinary medicine/psychiatry unit completed measures of functional impairment, depression, symptom severity, and the Ways of Coping Checklist--Revised. Hierarchical regression analyses indicated that emotion-focused coping was positively related to poor psychosocial adjustment and depression after controlling for physician rated disease severity. Appraising chronic illness as holding one back predicted greater emotion-focused coping responses and poorer adjustment to illness. The use of problem-focused coping strategies was generally unrelated to illness adjustment. These findings suggest the presence of an emotion-focused coping triad consisting of wishful thinking, self blame, and avoidance, all of which appear to be maladaptive strategies when coping with chronic medical conditions. Implications for coping skills training and the need for longitudinal research is discussed. PMID- 2222389 TI - The Agoraphobia Scale: an evaluation of its reliability and validity. AB - This article presents the Agoraphobia Scale (AS), and evidence for its reliability, validity, and sensitivity to change after treatment. The scale consists of 20 items depicting various typical agoraphobic situations, which are rated for anxiety/discomfort (0-4) and avoidance (0-2). The results show that AS has high internal consistency. Regarding concurrent validity it correlated significantly with other self-reported measures of agoraphobia (Mobility Inventory and Fear Questionnaire). The scale's predictive validity was shown as it correlated with avoidance behavior and self-rated anxiety during both an individualized and a standardized behavioral test of agoraphobia. The AS also discriminated between an agoraphobic sample and a normal sample, and a sample of simple phobia patients. Finally, it was sensitive to changes after behavioral treatment. The AS is useful both as a state, and as an outcome self-report measure of agoraphobia. PMID- 2222388 TI - Long-term follow-up of migraine treatment: do the effects remain up to six years? AB - Fifty migraine subjects (constituting 79% of the originally treated sample) participated in a follow-up study to 6 yr after the end of treatment. Subjects had been treated with different forms of biofeedback methods (skin temperature, BVP of the temporal artery) and applied relaxation training. The assessment included 4 weeks of continuous self-monitoring of headache activity and medication usage, as well as a retrospective self-rating scale. The main results indicated that, on a group basis, headache reductions achieved at the end of treatment persisted for up to 6 yr, and were indeed enhanced during the follow-up period. PMID- 2222391 TI - Maudsley Obsessional-Compulsive Inventory: obsessions and compulsions in a nonclinical sample. AB - Obsessive-compulsive disorder is increasingly being studied in nonclinical samples. The self-report instruments used to select these samples, however, have not been validated with a diagnostic interview. This study thus investigated the predictive validity of the Maudsley Obsessional-Compulsive Inventory (MOCI) using the Anxiety Disorders Interview Schedule (ADIS), a semi-structured interview created according to DSM-III guidelines. Four sections of the ADIS--generalized anxiety disorder, simple phobia, social phobia and obsessive-compulsive disorder- were administered to 11 individuals who scored in the top 2% and 11 individuals who scored in the normal range of the MOCI 6-7 months prior to the interview. High nonclinical MOCI scorers reported more frequent and severe obsessions and compulsions as well as greater disturbance by these symptoms. In addition, the high MOCI group experienced more general worry and interference from worry, and more frequent and severe physiological symptoms when they worry. However, the two groups did not differ in terms of simple and social phobia symptoms. High MOCI scorers thus did not report a broad range of anxiety symptoms or fears, but specific obsessions and compulsions. These results provide further support for the validity of the MOCI in nonclinical samples over a 6-7 month interval. PMID- 2222390 TI - Behaviorally treated irritable bowel syndrome patients: a four-year follow-up. AB - Nineteen of 27 patients suffering from Irritable Bowel Syndrome (IBS) who had completed a multicomponent treatment involving progressive muscle relaxation, thermal biofeedback, cognitive therapy and IBS education were located and evaluated 4 yr posttreatment. Seventeen of 19 (89.5, or 63% of the total original sample) rated themselves as more than 50% improved. Six of the 12 patients (50%) who submitted symptom monitoring diaries met our criteria for clinical improvement, i.e. achieving at least a 50% reduction in primary IBS symptom scores. The means on all measures at long-term follow-up were lower than those obtained prior to treatment. When follow-up symptom means were compared with pretreatment means, significant (P less than 0.05) reductions were obtained on abdominal pain/tenderness, diarrhea, nausea, and flatulence. PMID- 2222392 TI - Obsessions and compulsions: psychometric properties of the Padua Inventory with an American college population. AB - The psychometric properties of the Padua inventory, a self-report measure of obsessive-compulsive behaviors, were examined in a sample of 678 American college students. Results showed good internal consistency as well as convergent and divergent validity with the subscales of the Symptom Checklist-90 Revised and the Maudsley Obsessional-Compulsive Inventory. A principal components analysis suggested a four factor solution (i.e. 'impaired control of mental activities', 'checking', 'urges and worries of losing control of motor behaviors', and 'being contaminated'). The factor structure was very similar to that found in the original Italian study of the inventory. Suggestions are made for the use of the Padua Inventory in the study of obsessions and compulsions in nonclinical samples. PMID- 2222393 TI - The effectiveness of Dry Bed Training for nocturnal enuresis in adults. AB - Nine enuretic adults were successfully treated by the Dry Bed Training in a fairly short time (means = 15 weeks) including the retraining period for 3 Ss who relapsed after the therapy. There were no differences between primary and secondary (nocturnal) enuretics. The few relapses were neutralized by a short retraining. The study shows that this minimal intervention treatment is effective and efficient. PMID- 2222394 TI - Alcohol and correspondence between self-report and physiological measures of anxiety. AB - The present study was designed to determine the main effects of alcohol intoxication on self-report and physiological measures of anxiety. Second, we aimed to assess the role of the Marlowe-Crowne Social Desirability (MCSD) scale in predicting the relationship between self-report and physiological indices of anxiety irrespective of drink content. A final purpose of the study was to determine whether the MCSD could account for discrepancies in the effects of alcohol on the two anxiety response systems. Subjects were male social drinkers who received an 0.70 g/kg dose of alcohol or placebo. Results indicated that irrespective of drink content, subjects with high MCSD scores reported lower levels of anxiety than did subjects with low MCSD scores. This relationship was not evident for heart rate. These results for measures of anxiety were not influenced by drink content. PMID- 2222395 TI - Relationships between catastrophic cognitions and body sensations in anxiety disordered, mixed diagnosis, and normal subjects. AB - Clark's (Behaviour Research and Therapy, 24, 461-470, 1986) cognitive model proposes that panic attacks result from the catastrophic misinterpretation of certain body sensations. The present study examined correlations between feared body sensations and catastrophic cognitions. It was hypothesized that regardless of diagnostic status meaningful correlations between sensations and cognitions would be obtained. Three groups--anxiety disordered patients (n = 33), nonanxiety disordered patients (n = 57), and normals (n = 60)--completed the Agoraphobic Cognitions Questionnaire and the Body Sensations Questionnaire. Results generally supported the hypothesis and the cognitive model of panic and anxiety. Limitations of the correlational methodology are discussed, and treatment implications are noted. PMID- 2222396 TI - Heterogeneity of biofeedback training effects in spasmodic torticollis: a single case approach. AB - Data from 184 biofeedback sessions are presented, in which 10 subjects with spasmodic torticollis had been trained to reduce pathologic activity in the hypertrophied sternocleidomastoid muscle. Each session was conducted as a single case experiment with nine successive trials. Attempts were made to distinguish motor learning processes which can be elicited independently from the biofeedback condition from the effects of specific biofeedback information. Results showed dramatic decreases of muscle activity under biofeedback. Contrary to expectation, action potentials did not decrease across a course of 14 training sessions. Instead, effects were exhibited in an all-or-none fashion early in the training. Single-case ARIMA intervention analysis has shown that in 59% of the sessions EMG decreases demonstrated under biofeedback could be elicited prior to biofeedback in a condition of instructed control. Case studies revealed complex interactions of instructed control, specific biofeedback effects, unspecific effects of the biofeedback setting, and cognitive processes. Effects obtained within experimental sessions varied highly between subjects. Results are discussed in terms of newer concepts of basal ganglia dysfunction, and conclusions for the use of biofeedback paradigms in torticollis subjects are outlined. PMID- 2222397 TI - Analysis of GFA-protein mRNA expression in developing bovine brain by in situ hybridization and northern blot hybridization. AB - Using bovine brains of adult and developmental stages, the time and place of the appearance of mRNA for glial fibrillary acidic protein (GFA-protein) were studied by in situ- and Northern blot-hybridization. Double-stranded cDNA labeled with [3H]dCTP or [32P]dCTP was used as the probe for this mRNA. To compare the location of GFA-protein mRNA and GFA-protein itself on serial sections. GFA protein immunohistochemistry was used. By in situ hybridization with adult bovine brain. GFA-protein mRNA was detected in astroglia, most of which were in the white matter. The distribution of these astroglia by in situ hybridization was consistent with the findings by GFA-protein immunohistochemistry and Northern blot hybridization, indicating that each techniques were specific. Concerning fetal stages, GFA-protein mRNA could be detected in the brain of a fetal calf with a body length of 28 cm by in situ hybridization using the 32P-labeled probe, and the mRNA was localized in the subpial area and the fornix. These results indicated that glial maturation first became recognizable at least in the subpial area and the fornix in the brain of a fetal calf measuring 28 cm. In this fetal brain, GFA-protein mRNA was almost undetectable by Northern blot hybridization. This suggested that in situ hybridization was more sensitive and useful for the analysis of gene expression than Northern blot hybridization, when the target mRNA is present in only a limited area, such as in the brain. PMID- 2222398 TI - Hinf I restriction endonuclease digestion on human fixed metaphase chromosomes. AB - The authors report on the activity of Hinf I restriction endonuclease on human fixed metaphase chromosomes. Experiments performed by digesting chromosomes just after harvesting or after ageing in methanol-acetic acid displayed a different pattern of digestion on metaphases, since only aged preparations showed gaps on heterochromatic regions of chromosomes 1, 9 and 16 and C-like bands on other chromosomes. In this view, the authors suggest that structural modifications of the DNA, induced by acid fixation, can influence Hinf I activity on fixed metaphase chromosomes. PMID- 2222399 TI - Lectin binding to the egg envelopes in Eyprepocnemis plorans (Charp.) (Orthoptera, Acrididae). AB - The distribution of glycoconjugates in the egg envelopes of Eyprepocnemis plorans was investigated using various FITC-conjugated lectins. In the epichorion, the lectins ConA, SBA and WGA each have particular binding patterns, while TPA binding is confined to its deepest regions only. The glycoconjugates of the micropylar wall present different characteristics from those of the surrounding chorion. The vitelline coat shows a marked binding for WGA and TPA only; below the inner micropylar openings, this binding pattern is uniform over the whole extent of the coat and therefore it is not possible to identify specific binding sites for these two lectins. Contrary to what has been observed in some other insect species, the vitelline coat does not seem to be involved in the structural organization of the mycropyles. PMID- 2222400 TI - Langerhans cells in odontogenic tumours and cysts as detected by S-100 protein immunohistochemistry. AB - Immunohistochemical demonstration of S-100 protein in Langerhans cells (LCs) was made in odontogenic epithelial tumours (71 cases), radicular cysts (40 cases), follicular cysts (28 cases), odontogenic keratocysts (11 cases), primordial cysts (7 cases) and fissual cysts (6 cases). With the use of polyclonal antiserum against S-100 protein, positive LCs, dendrical or irregular in shape were found in tumour or cystic epithelia, and sometimes in stromal connective tissue. Incidence of positive S-100 staining LCs was 11 cases out of 61 ameloblastomas, 22 cases out of 40 radicular cysts, 3 cases of 28 follicular cysts, and other lesions in both odontogenic tumours and cystic diseases lacked LCs. The cases with S-100 protein positive LCs were usually accompanied with a high degree of inflammatory infiltration in their lesions; on the contrary, the negative cases also generally lacked inflammatory responses. PMID- 2222401 TI - Chromogranin A as a marker of neuroendocrine histogenesis of tumours: an immunoelectron microscopic study with considerations about the influence of fixation and embedding media on immunolabelling. AB - The ultrastructural localization of chromogranin A (Chr A) was studied in eleven neoplasias of the diffuse neuroendocrine system (3 pancreatic islet-cell tumours, 1 medullary carcinoma of the thyroid, 1 large bowel and 1 small bowel carcinoid tumours, 2 carcinoid tumours of the lung, 1 adenoma of the parathyroid gland, 2 pheochromocytomas of the adrenal gland). On account of the great influence of the technical treatment of the samples on the immunolocalization of Chr A, the effect of the following variables was studied in a case of pheochromocytoma: fixation in glutaraldehyde versus paraformaldehyde, postfixation in osmium tetroxide versus omission, embedding in epoxy resin versus acrylic resin. The method of choice for the better preservation of the antigenic character of the tissue was found to be fixation in 4% paraformaldehyde, omission of osmium postfixation and embedding in LRWhite acrylic resin; by this procedure we were able to find Chr A in the neurosecretory granules of all the studied cases, using three commercially available antibodies directed against Chr A. These findings further confirm that Chr A is a reliable marker for the study of neuroendocrine neoplasias by electron microscopy. PMID- 2222402 TI - A geometrical construction to assess scanning technique in microphotometry. PMID- 2222404 TI - Synthesis and secretion of active lipoprotein lipase in Chinese-hamster ovary (CHO) cells. AB - Cultured Chinese-hamster ovary cells (CHO cells) were found to produce and secrete a lipase, which was identified as a lipoprotein lipase by the following criteria. Its activity was stimulated by serum and apolipoprotein CII, and was inhibited by high salt concentration. The lipase bound to heparin-agarose and co eluted with 125I-labelled bovine lipoprotein lipase in a salt gradient. A chicken antiserum to bovine lipoprotein lipase inhibited the activity and precipitated a labelled protein of the same apparent size as bovine lipoprotein lipase from media of CHO cells labelled with [35S]methionine. The lipase activity and secretion were similar in growing cells and in cells that had reached confluency. Hence, lipoprotein lipase appears to be expressed constitutively in CHO cells and is not linked to certain growth conditions, as in pre-adipocyte and macrophage cell lines. At 37 degrees C, but not at 4 degrees C, heparin increased the release of lipase to the medium 2-4-fold. This increased release occurred without depletion of cell-associated lipase activity, suggesting that heparin enhanced release of newly synthesized lipase. PMID- 2222403 TI - The role of transferrin in the mechanism of cellular iron uptake. PMID- 2222406 TI - Reversible effects of sphingomyelin degradation on cholesterol distribution and metabolism in fibroblasts and transformed neuroblastoma cells. AB - Plasma-membrane sphingomyelin appears to be one of the major determinants of the preferential allocation of cell cholesterol into the plasma-membrane compartment, since removal of sphingomyelin leads to a dramatic redistribution of cholesterol within the cell [Slotte & Bierman (1988) Biochem. J. 250, 653-658]. In the present study we examined the long-term effects of sphingomyelin degradation on cholesterol redistribution in cells and determined the reversibility of the process. In a human lung fibroblast-cell line, removal of 80% of the sphingomyelin led to a rapid and transient up-regulation (3-fold) of acyl CoA:cholesterol acyltransferase (ACAT) activity, and also, within 30 h, to the translocation of about 50% of the cell non-esterified cholesterol from a cholesterol oxidase-susceptible compartment (i.e. the cell surface) to oxidase resistant compartments. At 49 h after the initial sphingomyelin degradation, the cell sphingomyelin level was back to 45% of the control level, and the direction of cell cholesterol flow was toward the cell surface, although the original distribution was not achieved. In a transformed neuroblastoma cell line (SH SY5Y), the depletion of sphingomyelin led to a similarly rapid and transient up regulation of ACAT activity, and to the translocation of about 25% of cell surface cholesterol into internal membranes (within 3 h). The flow of cholesterol back to the cholesterol oxidase-susceptible pool was rapid, and a pretreatment cholesterol distribution was reached within 20-49 h. Also, the resynthesis of sphingomyelin was faster in SH-SY5Y neuroblastoma cells and reached control levels within 24 h. The findings of the present study show that the cellular redistribution of cholesterol, as induced by sphingomyelin degradation, is reversible and suggest that the normalization of cellular cholesterol distribution is linked to the re-synthesis of sphingomyelin. PMID- 2222405 TI - Phenobarbital induction of cytochromes P-450. High-level long-term responsiveness of primary rat hepatocyte cultures to drug induction, and glucocorticoid dependence of the phenobarbital response. AB - The induction of hepatic cytochromes P-450 by phenobarbital (PB) was studied in rat hepatocytes cultured for up to 5 weeks on Vitrogen-coated plates in serum free modified Chee's medium then exposed to PB (0.75 mM) for an additional 4 days. Immunoblotting analysis indicated that P-450 forms PB4 (IIB1) and PB5 (IIB2) were induced dramatically (greater than 50-fold increase), up to levels nearly as high as those achieved in PB-induced rat liver in vivo. The newly synthesized cytochrome P-450 was enzymically active, as shown by the major induction of the P-450 PB4-dependent steroid 16 beta-hydroxylase and pentoxyresorufin O-dealkylase activities in the PB-induced hepatocyte microsomes (up to 90-fold increase). PB induction of these P-450s was markedly enhanced by the presence of dexamethasone (50 nM-1 microM), which alone was not an affective inducing agent, and was inhibited by greater than 90% by 10% fetal bovine serum. The PB response was also inhibited (greater than 85%) by growth hormone (250 ng/ml), indicating that this hormone probably acts directly on the hepatocyte when it antagonizes the induction of P-450 PB4 in intact rats. In untreated hepatocytes, P-450 RLM2 (IIA2), P-450 3 (IIA1) and NADPH P-450 reductase levels were substantially maintained in the cultures for 10-20 days. The latter two enzymes were also inducible by PB to an extent (3-4 fold elevation) that is comparable with that observed in the liver in vivo. Moreover, P-450c (IA1) and P 450 3 (IIA1) were highly inducible by 3-methylcholanthrene (5 microM; 48 h exposure) even after 3 weeks in culture. In contrast, the male-specific pituitary regulated P-450 form 2c (IIC11) was rapidly lost upon culturing the hepatocytes, suggesting that supplementation of appropriate hormonal factors may be necessary for its expression. The present hepatocyte culture system exhibits a responsiveness to drug inducers that is qualitatively and quantitatively comparable with that observed in vivo, and should prove valuable for more detailed investigations of the molecular and mechanistic basis of the response to PB and its modulation by endogenous hormones. PMID- 2222407 TI - Uptake and metabolism of dipeptides by human red blood cells. AB - A function of the abundant cytoplasmic peptidases in red blood cells could be hydrolysis of oligopeptides circulating in plasma. To investigate whether human red blood cells actively transport dipeptides for this purpose, these cells were incubated with 14C-labelled glycylproline, glycylsarcosine, glycine, proline and alanine. There was uptake of each dipeptide, as indicated by their recovery as dipeptides in the cell cytoplasm. However, after a brief time (1-2 min) uptake of dipeptides abruptly ceased, while that of amino acids continued. As a result, after 30 min red blood cell uptake of amino acids was 5-13-fold greater than that of any dipeptide. Investigation of intracellular contents after 1 min of incubation revealed different metabolism for different dipeptides. The composition of intracellular radioactivity was 19-71% as intact dipeptides, 0-20% as free amino acids and 8-77% as neither dipeptides nor constituent amino acids. Investigation of the mechanism of dipeptide uptake by red blood cells showed: (1) a lack of hydrolysis by the plasma membrane, (2) no non-specific binding to the plasma membrane, and (3) a lack of saturation over a wide range of concentrations (0.05-50 mM). The data suggest that the mechanism of uptake of trace amounts of dipeptides by human red blood cells is either by simple diffusion or by a carrier system which has a very weak affinity for dipeptides. Upon entry, depending on the molecular structure, dipeptides are either hydrolysed or transformed into new compounds. The red blood cell uptake, however, does not appear to play any appreciable role in clearance of dipeptides from the plasma in the human. PMID- 2222408 TI - Identification of a single base change in a new human mutant glucose-6-phosphate dehydrogenase gene by polymerase-chain-reaction amplification of the entire coding region from genomic DNA. AB - We report the characterization at the molecular level of a mutant glucose-6 phosphate dehydrogenase (G6PD) gene in a Greek boy who presented with a chronic non-spherocytic haemolytic anaemia. In order to identify the mutation from a small amount of patient material, we adopted an approach which by-passes the need to construct a library by using the polymerase chain reaction. The entire coding region was amplified in eight sections, with genomic DNA as template. The DNA fragments were then cloned in an M13 vector and sequenced. The only difference from the sequence of normal G6PD was a T----G substitution at nucleotide position 648 in exon 7, which predicts a substitution of leucine for phenylalanine at amino acid position 216. This mutation creates a new recognition site for the restriction nuclease BalI. We confirmed the presence of the mutation in the DNA of the patient's mother, who was found to be heterozygous for the new BalI site. This is the first transversion among the point mutations thus far reported in the human G6PD gene. PMID- 2222409 TI - Inhibition and recognition studies on the glutathione-binding site of equine liver glutathione S-transferase. AB - Equine liver glutathione S-transferase has been shown to consist of two identical subunits of apparent Mr 25,500 and a pl of 8.9. Kinetic data at pH 6.5 with 1 chloro-2,4-dinitrobenzene as a substrate suggests a random rapid-equilibrium mechanism, which is supported by inhibition studies using glutathione analogues. S-(p-Bromobenzyl)glutathione and the corresponding N alpha-, CGlu- and CGly substituted derivatives have been found, at pH 6.5, to be linear competitive inhibitors, with respect to GSH, of glutathione transferase. N-Acetylation of S (p-bromobenzyl)glutathione decreases binding by 100-fold, whereas N-benzoylation and N-benzyloxycarbonylation abolish binding of the derivative to the enzyme. The latter effect has been attributed to a steric constraint in this region of the enzyme. Amidation of the glycine carboxy group of S-(p-bromobenzyl)glutathione decreases binding by 13-fold, whereas methylation decreases binding by 70-fold, indicating a steric constraint and a possible electrostatic interaction in this region of the enzyme. Amidation of both carboxy groups decreases binding significantly by 802-fold, which agrees with electrostatic interaction of the glutamic acid carboxy group with a group located on the enzyme. PMID- 2222410 TI - Synthesis of carboxy-residue-modified coenzyme derivatives as probes to the mechanism of glutathione enzymes. AB - a general procedure for the preparation of the monoglycyl and dimethyl ester and amide derivatives of s-(4-bromobenzyl)glutathione are reported, in addition to purification procedures. PMID- 2222411 TI - Effects of variation in glutathione peroxidase activity on DNA damage and cell survival in human cells exposed to hydrogen peroxide and t-butyl hydroperoxide. AB - The selenium-dependent glutathione peroxidase activities of two human cell lines, the colon carcinoma HT29 and the mesothelioma P31, cultured in medium containing 2% serum, increased from 195 to 541 and from 94 to 361 units/mg of protein respectively after supplementation with 100 nM-selenite. The catalase activity remained unchanged by this treatment. The effects of the obtained variation in glutathione peroxidase activities were investigated by exposing cells to H2O2 and t-butyl hydroperoxide. Selenite supplementation resulted in a decrease in H2O2 induced DNA single-strand breaks in both HT29 and P31 cells. A small, but significant, decrease in the number of DNA single-strand breaks for low doses (10 50 microM) of t-butyl hydroperoxide was found only in P31 cells and not in HT29 cells. We could detect neither induction of double-strand breaks (detection limit approx. 1000 breaks per cell) nor DNA-protein cross-links after exposing the cells to the two peroxides. In spite of the apparent protective effect of increased glutathione peroxidase activity on DNA single-strand break formation, there were no differences between selenite-supplemented and non-supplemented cells in cell survival after exposure to peroxide. PMID- 2222412 TI - Highly purified bile-canalicular vesicles and lateral plasma membranes isolated from rat liver on Nycodenz gradients. Biochemical and immunolocalization studies. AB - 1. A liver canalicular plasma-membrane fraction enriched 115-155-fold in five marker enzymes relative to the tissue homogenate was obtained by sonication of liver plasma membranes followed by fractionation in iso-osmotic Nycodenz gradients. 2. Two lateral-plasma membrane fractions were also collected by this procedure; the lighter-density fraction was still associated with canalicular membranes, as assessed by enzymic and polypeptide analysis. 3. The polypeptide composition of the domain-defined plasma-membrane fractions was evaluated. It was demonstrated by immunoblotting that the 41 kDa alpha-subunit of the inhibitory G protein, associated in high relative amounts with canalicular plasma-membrane fractions, was partially lost in the last stage of purification; however, this subunit was retained by lateral plasma membranes. 4. Antibodies to the proteins of bile-canalicular vesicles were shown to localize to the hepatocyte surface in thin liver sections examined by immunofluorescent and immuno-gold electron microscopy. Two subsets of antigens were identified, one present on both sinusoidal and canalicular plasma-membrane domains and another, by using antisera pre-absorbed with sinusoidal plasma membranes, that was confined to the bile canalicular domain. PMID- 2222413 TI - Differential regulation of the HepG2 and adipocyte/muscle glucose transporters in 3T3L1 adipocytes. Effect of chronic glucose deprivation. AB - Glucose transport in 3T3L1 adipocytes is mediated by two facilitated diffusion transport systems. We examined the effect of chronic glucose deprivation on transport activity and on the expression of the HepG2 (GLUT 1) and adipocyte/muscle (GLUT 4) glucose transporter gene products in this insulin sensitive cell line. Glucose deprivation resulted in a maximal increase in 2 deoxyglucose uptake of 3.6-fold by 24 h. Transport activity declined thereafter but was still 2.4-fold greater than the control by 72 h. GLUT 1 mRNA and protein increased progressively during starvation to values respectively 2.4- and 7.0 fold greater than the control by 72 h. Much of the increase in total immunoreactive GLUT 1 protein observed later in starvation was the result of the accumulation of a non-functional or mistargeted 38 kDa polypeptide. Immunofluorescence microscopy indicated that increases in GLUT 1 protein occurred in presumptive plasma membrane (PM) and Golgi-like compartments during prolonged starvation. The steady-state level of GLUT 4 protein did not change during 72 h of glucose deprivation despite a greater than 10-fold decrease in the mRNA. Subcellular fractionation experiments indicated that the increased transport activity observed after 24 h of starvation was principally the result of an increase in the 45-50 kDa GLUT 1 transporter protein in the PM. The level of the GLUT 1 transporter in the PM and low-density microsomes (LDM) was increased by 3.9- and 1.4-fold respectively, and the GLUT 4 transporter content of the PM and LDM was 1.7- and 0.6-fold respectively greater than that of the control after 24 h of glucose deprivation. These data indicate that newly synthesized GLUT 1 transporters are selectively shuttled to the PM and that GLUT 4 transporters undergo translocation from an intracellular compartment to the PM during 24 h of glucose starvation. Thus glucose starvation results in an increase in glucose transport in 3T3L1 adipocytes via a complex series of events involving increased biosynthesis, decreased turnover and subcellular redistribution of transporter proteins. PMID- 2222414 TI - Determination by photoaffinity labelling of the hydrophobic part of the binding site for acyl-CoA esters on acyl-CoA-binding protein from bovine liver. AB - Acyl-CoA esters containing the photoreactive acids 12-(4'-azido-2' nitrophenoxy)[1-14C]dodecanoic acid ([14C]AND-acid) or N-(4'-azido-2'-nitro-[3' 5'-3H]phenyl)-12-aminododecanoic acid ([3H]NANPA-acid) were synthesized. The photoreactive acyl-CoA esters could be bound to bovine acyl-CoA-binding protein (ACBP) and photocrosslinked to the protein. The photocrosslinked acyl-CoA-ACBP complex was separated from unlabelled ACBP on reverse-phase h.p.l.c. and the purified complex was digested with trypsin, Staphylococcus aureus V8 proteinase or endoproteinase Asp-N. By four independent peptide maps it was shown that the amino acids taking part in forming the hydrophobic binding site for acyl-CoA esters in bovine ACBP are located on the peptide segment from Asp21 to Asp38. Both photoreactive acyl-CoA esters used in this study labelled strongly in the segment from Tyr28 to Ala34. 12-(4'-Azido-2'-nitrophenoxy)[1-14C]-dodecanoyl-CoA ([14C]AND-CoA) also introduced a label at position Asp38, but o labelling was found before Ser29. In contrast, N-(4'-azido-2'-nitro[3',5'-3H]phenyl)-12 aminododecanoyl-CoA [3H]NANPA-CoA) also labelled the segment from Asp21 to Tyr28. The difference in labelling by the two photoreactive ligands is most likely caused by different mobility of the arylazido group when linked to the fatty acid either through a phenolic O- or an anilinic N- bond. PMID- 2222415 TI - There are two major types of skeletal keratan sulphates. AB - High-field 1H-n.m.r.-spectroscopic studies supported by chemical carbohydrate analyses show that skeletal keratan sulphates (KS-II) of bovine origin may be sub classified into two groups. Keratan sulphate chains from articular and intervertebral-disc cartilage (KS-II-A) contain two structural features, namely alpha(1----3)-fucose and alpha(2----6)-linked N-acetyl-neuraminic acid residues, that are absent from keratan sulphates from tracheal or nasal-septum cartilage (KS-II-B). PMID- 2222416 TI - Liberation of tryptic fragments from caseinomacropeptide of bovine kappa-casein involved in platelet function. Kinetic study. AB - Carbohydrate-free caseinomacropeptide (CMP) was purified from rennet-hydrolysed caseinate by trichloroacetic acid precipitation and DEAE-TSK Fractogel-650 ion exchange chromatography. To study the liberation of 106-112, 106-116 and 113-116 fragments from carbohydrate-free CMP involved in platelet function, a quantitative study was made on the rate of hydrolysis of the three peptidic bonds that are susceptible to the action of trypsin. Data were obtained from reverse phase (Ultrabase column) and cationic-exchange (Mono S column) h.p.l.c. On the basis of the disappearance of substrate, kcat. and Km were respectively 3.95 s-1 and 0.2 mM. The two 111-112 and 112-113 bonds were split according to similar kinetic parameters (kcat. = 1.97 s-1, Km = 0.2 mM) and much faster than the 116 117 bond. The difference in susceptibility of the bonds can probably be attributed to the nature of residues flanking the primary proteolytic sites rather than to their accessibility to the proteinase. On the basis of our results the 106-116 fragment cannot be formed. PMID- 2222417 TI - Use of ATP, dATP and their alpha-thio derivatives to study DNA ligase adenylation. AB - Bacteriophage-T4 and human type I DNA ligases were found capable of self adenylating upon exposure to both ribo- and deoxyribo-[alpha-35S]thio-ATP. However, the joining reaction does not take place in the presence of the deoxyribotriphosphates. Enzyme adenylation is reversed in all cases by an excess of PPi, but the rate of reversion is lower with thio derivatives. Therefore thio derivatives can be used to study the adenylation of DNA ligases and to search for specific inhibitors of the first step of the ligation reaction. In addition we show that thio derivatives can be used to detect DNA ligase adenylation activity covalently bound to a solid matrix. PMID- 2222418 TI - Effect of local anaesthetics on mitochondrial membrane potential in living cells. AB - Using the laser dye rhodamine 123, we demonstrated that local anaesthetics can reach mitochondria in cell culture and reversibly decrease, or even collapse, their transmembrane potential. This effect is highly dependent on the lipid solubility of the local anaesthetic and can be facilitated by the presence of a lipophilic anion. PMID- 2222419 TI - Evidence by chemical modification that tryptophan-104 of the cysteine-proteinase inhibitor chicken cystatin is located in or near the proteinase-binding site. AB - The single tryptophan residue Trp-104 of chicken cystatin was modified with a 2 hydroxy-5-nitrobenzyl group. The change of the absorption spectrum of this group on binding of the modified cystatin to papain indicated a decreased environmental polarity of the probe. The modified inhibitor had about a 10(5)-fold lower affinity for papain than had intact cystatin, this being due to a higher dissociation rate constant. These results show that Trp-104 of cystatin is located in or near the proteinase-binding site of the inhibitor, in agreement with a model proposed from computer docking Experiments. PMID- 2222420 TI - Expression and processing of procholecystokinin in a rat medullary thyroid carcinoma cell line. AB - A rat medullary thyroid carcinoma cell line, CA-77, was shown to express the cholecystokinin (CCK) gene. Measurements using a library of sequence-specific radioimmunoassays before and after enzymic treatment of extracts and chromatographic fractions showed that the cells contained 1.0 pmol of alpha carboxyamidated cholecystokinins/10(6) cells, 0.4 pmol of glycine-extended intermediates/10(6) cells and 1.0 pmol of further C-terminal-extended pro CCK/10(6) cells. Gel chromatography and reverse-phase h.p.l.c. revealed both sulphated and nonsulphated CCK-8 in the cells. The growth medium contained in addition alpha-amidated CCK-33, glycine-extended CCK-8 and pro-CCK. Exposure to 0.1 microM-dexamethasone for 6 days increased the cellular content and secretion of all of the described CCK peptides by 2-3-fold. The increase was first noted after 3 days of treatment. Monensin inhibited the synthesis of alpha carboxyamidated CCK and the secretion of all of the CCK forms measured. Colchicine at a low concentration (0.2 mumol/l) apparently increased the synthesis and secretion of alpha-carboxyamidated CCK, whereas higher concentrations inhibited CCK synthesis. Finally, chloroquine inhibited the alpha carboxyamidation of CCK. We conclude that the CA-77 cell line is a useful tool for studies of the expression and post-translational processing of pro-CCK. PMID- 2222421 TI - Lipoamidase is a multiple hydrolase. AB - The substrate specificity of lipoamidase, purified from the pig brain membrane with lipoyl 4-aminobenzoate (LPAB) as a substrate, was extensively studied. This single polypeptide was found to hydrolyse the bonding between amide, ester and peptide compounds. However, stringent structural requirements were found in the substrates, e.g. LPAB was hydrolysed, whereas biotinyl 4-aminobenzoate was not, as stated in our previous paper [Oizmui & Hayakawa (1990) Biochem. J. 266, 427 434]. The enzyme specifically recognized the whole molecular structure of the substrate, whereas it loosely recognized the bond structure of the substrate; e.g. the dipeptide Asp-Phe was not hydrolysed, whereas the methyl ester of Asp Phe (aspartame) was. The exopeptidase activity was demonstrated by lipoamidase; however, longer peptides than the hexamer seemed not to be substrates. Lipoyl esters, which were electrically neutral, exhibited higher specificity with longer acyl groups. Molecular mass and molecular hydrophobicity (hydropathy) seemed to determine the substrate specificity. Lipoyl-lysine, acetylcholine and oligopeptides were hydrolysed at similar Km values; however, acetylcholine was hydrolysed at a velocity 100 times higher. Although many similar specificities were found between electric eel acetylcholinesterase and lipoamidase, distinctly different specificity was demonstrated with lipoyl compounds. The role of lipoamidase, which resides on the brain membrane and possesses higher specificity for hydrophobic molecules, remains to be elucidated. PMID- 2222424 TI - Formation of the lignan, (-) secoisolariciresinol, by cell free extracts of Forsythia intermedia. AB - A crude cell-free extract from Forsythia intermedia catalyses the formation of ( )secoisolariciresinol, and not its (+) enantiomer, when incubated with coniferyl alcohol in the presence of NAD(P)H and H2O2. This is the first report of an enzyme reaction specifically involved in the coupling reaction between two phenylpropanoid monomers to afford an optically pure lignan. PMID- 2222422 TI - Human liver iduronate-2-sulphatase. Purification, characterization and catalytic properties. AB - Human iduronate-2-sulphatase (EC 3.1.6.13), which is involved in the lysosomal degradation of the glycosaminoglycans heparan sulphate and dermatan sulphate, was purified more than 500,000-fold in 5% yield from liver with a six-step column procedure, which consisted of a concanavalin A-Sepharose-Blue A-agarose coupled step, chromatofocusing, gel filtration on TSK HW 50S-Fractogel, hydrophobic separation on phenyl-Sepharose CL-4B and size separation on TSK G3000SW Ultrapac. Two major forms were identified. Form A and form B, with pI values of 4.5 and less than 4.0 respectively, separated at the chromatofocusing step in approximately equal amounts of recovered enzyme activity. By gel-filtration methods form A had a native molecular mass in the range 42-65 kDa. When analysed by SDS/PAGE, dithioerythritol-reduced and non-reduced form A and form B consistently contained polypeptides of molecular masses 42 kDa and 14 kDa. Iduronate-2-sulphatase was purified from human kidney, placenta and lung, and form A was shown to have similar native molecular mass and subunit components to those observed for liver enzyme. Both forms of liver iduronate-2-sulphatase were active towards a variety of substrates derived from heparin and dermatan sulphate. Kinetic parameters (Km and Kcat) of form A were determined with a variety of substrates matching structural aspects of the physiological substrates in vivo, namely heparan sulphate, heparin and dermatan sulphate. Substrate with 6 sulphate esters on the aglycone residue adjacent to the iduronic acid 2-sulphate residue being attack were hydrolysed with catalytic efficiencies up to 200 times above that observed for the simplest disaccharide substrate without a 6-sulphated aglycone residue. The effect of incubation pH on enzyme activity towards the variety of substrates evaluated was complex and dependent on substrate aglycone structure, substrate concentration, buffer type and the presence of other proteins. Sulphate and phosphate ions and a number of substrate and product analogues were potent inhibitor of form A and form B enzyme activities. PMID- 2222423 TI - The endogenous functional turkey erythrocyte and rat liver insulin receptor is an alpha 2 beta 2 heterotetrameric complex. AB - Previous studies have indicated that turkey erythrocyte and rat liver membranes contain endogenous alpha beta heterodimeric insulin receptors in addition to the disulphide-linked alpha 2 beta 2 heterotetrameric complexes characteristic of most cell types. We utilized 125I-insulin affinity cross-linking to examine the structural properties of insulin receptors from rat liver and turkey erythrocyte membranes prepared in the absence and presence of sulphydryl alkylating agents. Rat liver membranes prepared in the absence of sulphydryl alkylating agents displayed specific labelling of Mr 400,000 and 200,000 bands, corresponding to the alpha 2 beta 2 heterotetrameric and alpha beta heterodimeric insulin receptor complexes respectively. In contrast, affinity cross-linking of membranes prepared with iodoacetamide (IAN) or N-ethylmaleimide identified predominantly the alpha 2 beta 2 heterotetrameric insulin receptor complex. Similarly, affinity cross linking and solubilization of intact turkey erythrocytes in the presence of IAN resulted in exclusive labelling of the alpha 2 beta 2 heterotetrameric insulin receptor complex, whereas in the absence of IAN both alpha 2 beta 2 and alpha beta species were observed. Turkey erythrocyte alpha 2 beta 2 heterotetrameric insulin receptors from IAN-protected membranes displayed a 3-4-fold stimulation of beta subunit autophosphorylation and substrate phosphorylation by insulin, equivalent to that observed in intact human placenta insulin receptors. Turkey erythrocyte alpha beta heterodimeric insulin receptors, prepared by defined pH/dithiothreitol treatment of IAN-protected membranes, were also fully competent in insulin-stimulated protein kinase activity compared with alpha beta heterodimeric human placenta receptors. In contrast, endogenous turkey erythrocyte alpha beta heterodimeric insulin receptors displayed basal protein kinase activity which was insulin-insensitive. These data indicate that native turkey erythrocyte and rat liver insulin receptors are structurally and functionally similar to alpha 2 beta 2 heterotetrameric human placenta insulin receptors. The alpha beta heterodimeric insulin receptors previously identified in these tissues most likely resulted from disulphide bond reduction and denaturation of the alpha 2 beta 2 holoreceptor complexes during membrane preparation. PMID- 2222425 TI - Electroporation of rat pituitary (GH) cell lines: optimal parameters and effects on endogenous hormone production. AB - An efficient electroporation procedure was established for the genetic transformation of two clonal strains of hormone producing rat pituitary cells (GH12C1 and GH3). We used the bacterial chloramphenicol acetyltransferase (CAT) gene as reporter gene to determine optimal conditions for electroporation. The conditions found to be optimal, measured as expression of the highest CAT activity, were 240-300 V and a DNA concentration of 30-60 micrograms/ml in sucrose buffer. Cell viability was then about 50 per cent. Maximum CAT activity was seen 24 hours after electroporation. The electroporation procedure, in the presence or absence of DNA, caused a transient decrease in endogenous growth hormone (GH) and prolactin (PRL) production. PMID- 2222427 TI - 1,25(OH)2D3 and calcipotriol (MC903) have similar effects on the induction of osteoclast-like cell formation in human bone marrow cultures. AB - MC903 is a novel analogue of 1,25(OH)2D3 which exhibits similar inhibitory effects on cell proliferation and like, 1,25(OH)2D3, stimulates synthesis of osteoblast specific proteins by osteoblast-like cells in vitro. It is less active than 1,25(OH)2D3 in causing hypercalcemia in vivo. Since 1,25(OH)2D3 is known to stimulate bone resorption and increase the number of osteoclasts in several systems (in vivo and in vitro) we examined the effects of MC903 on the formation of osteoclast-like cells in vitro. As reported previously 1,25(OH)2D3 promoted the formation of multinucleated cells with phenotypic and functional characteristics of osteoclasts from adult human bone-marrow cultures at concentrations between 10(-8)M to 10(-12)M. Higher doses consistently suppressed multinucleated cell formation to values seen in the absence of 1,25(OH)2D3. Cells cultured in the presence of MC903 or for three weeks consistently induced the formation of multinucleated cells at concentrations 10(-8)M to 10(-12)M. As seen with 1,25(OH)2D3, MC903 also inhibited multinucleated cell formation at very high concentrations (10(-6)M). In two separate experiments MC903 appeared to be more potent than 1,25(OH)2D3 at lower concentrations (10(-10)M - 10(-12)M). From this study we conclude that MC903 is at least as potent as 1,25(OH)2D3 in inducing the formation human osteoclast-like cells in vitro. The decreased ability of MC903 to induce hypercalcemia in vivo is not therefore a result of a less marked effect than 1,25(OH)2D3 on the regulation of osteoclast formation. PMID- 2222426 TI - The Ca-MOv18 molecule, a cell-surface marker of human ovarian carcinomas, is anchored to the cell membrane by phosphatidylinositol. AB - The structure of the 38 kD cell surface glycoprotein identified by the monoclonal antibody MOv18 and specifically expressed by human ovarian carcinomas has been investigated at a molecular level. The ovarian carcinoma cell line IGROV-1, which expresses high levels of Ca-MOv18, was treated with the phosphatidylinositol specific phospholipase C from B. thuringiensis. The phospholipase C specifically released most of the Ca-MOv18 molecules as shown by flow cytometric analysis of the treated cells and by radioimmunometric assays of the corresponding supernatants. Consistent with the known structure of other phosphatidylinositol linked molecules, Ca-MOv18 was biosynthetically labeled by [3H]ethanolamine and the labeled molecules were immunoprecipitated from the supernatant fo the phospholipase C treated cells. Evidence that Ca-MOv18 is anchored to the cell membrane via phosphatidylinositol may prove to be relevant in current investigations regarding the biological and clinical significance of this tumor marker. PMID- 2222428 TI - Protein kinase C subspecies in estrogen receptor-positive and -negative human breast cancer cell lines. AB - Estrogen receptor-positive (MCF7) and -negative (BT20) human breast cancer cell lines, which are frequently used for studies on cancer chemotherapy with triphenylethylene (TPE) anti-estrogens, express at least three protein kinase C subspecies. Two of them are identified as type II PKC having the beta-sequence and type III PKC having the alpha-sequence. The other one shows typical characteristics of PKC which responds to Ca2+, phosphatidylserine and diacylglycerol, but shows kinetic properties subtly different from the previously known PKC subspecies. Immunoblot analysis has shown that this enzyme does not correspond to any of the well defined subspecies with known sequence structures. All of these PKC subspecies are similarly susceptible to the TPE antiestrogens. PMID- 2222429 TI - Possible contribution of protein kinase C activation to priming for DNA synthesis induced by epidermal growth factor with insulin and its inhibition by plasma membrane in primary cultured rat hepatocytes. AB - In primary cultured rat hepatocytes, DNA synthesis was markedly induced 48 h after plating by epidermal growth factor (EGF) and insulin added at 24 h, but not by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). When EGF and insulin were added at 6 h, DNA synthesis at 30 h was 7% of DNA synthesis seen at 48 h, but became 27% by pretreatment with TPA. The similar pretreatment effect was also seen with vasopressin. Such induction at 30 h was inhibited by rat liver plasma membrane added at 2 h even in the presence of TPA or vasopressin, and also by 1-(5 isoquinolinyl-sulfonyl)-2-methylpiperazine more extensively than N-(2 guanidinoethyl)-5-isoquinolinesulfonamide. These results suggest that DNA synthesis induction by EGF and insulin may require a priming period related to protein kinase C activation in primary cultured rat hepatocytes, which is inhibited by plasma membrane. PMID- 2222430 TI - Effects of metoclopramide on rat spleen lymphocyte proliferation. AB - The effect of metoclopramide on proliferation of spleen lymphocytes in rats was examined. The rate of [3H]thymidine incorporation into DNA was used as an index of lymphocytes proliferation. It was shown that the incorporation of [3H]thymidine into DNA of spleen lymphocytes in the rats treated with metoclopramide was significantly higher than that in the control group. The effects of various concentrations of prolactin and metoclopramide on [3H]thymidine uptake by DNA of spleen lymphocytes was also studied in vitro. It was shown that: 1, Prolactin, at the concentration of 1 and 0.1 ng/ml significantly increased [3H]thymidine incorporation into DNA of spleen lymphocytes. Metoclopramide in all the examined concentrations also caused a significant proliferogenic effect on lymphocytes. PMID- 2222431 TI - Tauroursodeoxycholic acid inhibits the cytosolic Ca++ increase in human neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine. AB - The effect of the cytoprotective bile acid tauroursodeoxycholic acid (TUDCA) on basal cytosolic free Ca++ (Ca++)i and receptor-mediated (Ca++)i increase was studied in human polymorphonuclear neutrophils using the fluorescent dye quin2. Basal levels of (Ca++)i were 96 +/- 6 nmol/l (mean +/- SEM, n = 48). TUDCA and its cytotoxic epimer taurochenodeoxycholic acid (TCDCA) at 500 mumols/l increased (Ca++)i by 31 +/- 12 and 27 +/- 7 nmol/l, respectively (n = 6, p less than 0.05). Stimulation of neutrophils with the chemotactic tripeptide N-formyl-methionyl leucyl-phenylalanine (FMLP; 10(-7) mol/l) induced a (Ca++)i increase of 200 +/- 32 nmol/l which was inhibited after preincubation with TUDCA (500 mumols/l) or TUDCA + TCDCA (500 mumols/l, each) by 60.1% and 59.5%, respectively, but not with TCDCA (500 mumols/l) alone. The inhibitory effect of TUDCA on FMLP-induced (Ca++)i increase was strongly concentration-dependent and was nearly complete at 1000 mumols/l. Since (Ca++)i is discussed as a mediator of cellular injury we hypothesize that TUDCA may exert its protective effects at least partly via inhibition of (Ca++)i-mediated cytotoxic processes. PMID- 2222432 TI - Translation of hepatitis B virus DNA polymerase from the internal AUG codon, not from the upstream AUG codon for the core protein. AB - Hepatitis B virus DNA replicates via its own polymerase that also acts as reverse transcriptase (Summers and Mason, 1982). This enzyme is encoded by a 3.5 Kb mRNA transcript covering the whole genome. Since the same transcript also codes for the core protein, and since the core open reading frame (ORF) is located upstream of the pol ORF, it has been suggested that the polymerase is first produced as a core-pol fusion protein that subsequently undergoes cleavage. This is already known to be the case with retrovirus reverse transcriptase, for which a gag-pol fusion protein is made first and the latter protein is liberated by proteolytic cleavage. We investigated this problem using mutants that were modified at the translation initiation codon for the core and precore ORF. Our findings suggested that polymerase translation occurred from the internal AUG codon independently of core protein synthesis, and that obligatory production of the core-pol fusion protein is accordingly unlikely. PMID- 2222433 TI - Regulation of ion uptake in membrane vesicles from rat brain by thiamine compounds. AB - We examined the effects of thiamine derivatives on ion uptake in rat brain membrane vesicles. Thiamine triphosphate (1 mM) and pyrithiamine (0.1 mM) increase chloride uptake. Preincubation of crude homogenate with thiamine or pyrithiamine increases chloride uptake while oxythiamine has the reverse effect. Thiamine and oxythiamine also affect 22Na+ and 86Rb+ uptake in the same way as for 36Cl- but to a lesser extent. Thiamine-dependent 36Cl- uptake is activated by sodium bicarbonate (10 mM) and partially inhibited by bumetanide (0.1 mM) and 2,4 dinitrophenol (0.1 mM). Preincubation with thiamine increases the thiamine triphosphate content of the vesicles. The hypothesis that TTP is the activator of a particular chloride uptake mechanism is discussed. PMID- 2222434 TI - Sequence analysis of the promoter region of the glioblastoma derived T cell suppressor factor/transforming growth factor (TGF)-beta 2 gene reveals striking differences to the TGF-beta 1 and -beta 3 genes. AB - Human glioblastoma cells secrete a factor termed glioblastoma derived T cell suppressor factor (G-TsF) or transforming growth factor beta 2 (TGF-beta 2) which inhibits the response of T cells to mitogenic or antigenic stimulation. In the present study we isolated the promoter region of the G-TsF/TGF-beta 2 gene. The promoter region shares no homology to the promoter of the TGF-beta 1 or the 5' region of the TGF-beta 3 gene and harbours several familiar DNA motifs, including the cytokine-1 region, an octamer-like sequence, Sp1- and AP-2-like elements and a putative NF-kappa B site. In contrast to the TGF-beta 1 gene, the G-TsF/TGF beta 2 gene contains three TATA-like sequences but lacks an AP-1 site. To understand the cell type specificity of expression of G-TsF/TGF-beta 2, the individual contribution of the DNA elements detected in the promoter has to be analysed in further studies. PMID- 2222435 TI - A molecular model for the enzyme cytochrome P450(17 alpha), a major target for the chemotherapy of prostatic cancer. AB - The enzyme cytochrome P450(17 alpha) catalyses two key steps in the biosynthesis of the androgens from pregnanes: the 17 alpha hydroxylation step and the subsequent 17-20 lyase reaction. Using a variety of techniques, including sequence alignment, secondary structure prediction, molecular mechanics and molecular dynamics, we have constructed a model for the three-dimensional structure of P450(17 alpha) based on that of P450cam, the only cytochrome P450 enzyme for which the crystal structure is known. The model suggests the possibility of two modes of binding of steroid substrates at the active site, perhaps reflecting the dual functionality of the enzyme. PMID- 2222436 TI - Penicillin binding proteins of Vibrio cholerae. AB - Eleven penicillin binding proteins (PBPs) of Vibrio cholerae have been identified using [125I] labelled p-hydroxybenzyl penicillin (PenX). These proteins are localised in the inner membrane and have molecular weights ranging from 97,000 to 22,000. Neutral hydroxylamine released the labelled PenX from the PBPs and pretreatment with cold benzyl penicillin inhibited labelling completely. The PBP 4 is the most sensitive target for cephaloridine and aztreonam. Cephaloridine also binds to three other high molecular weight PBPs, 1, 2 and 3. Aztreonam, in addition to PBP 4, has affinity for another low molecular weight PBP, PBP 7. Mecillinam has affinity for PBPs 1, 4 and 11. PMID- 2222437 TI - Inhibition of myosin light chain phosphorylation in cultured smooth muscle cells by HA1077, a new type of vasodilator. AB - When cultured smooth muscle cells were stimulated sequentially by concanavalin A and fetal calf serum, the cells rounded up, and there was an accompanying mono- and diphosphorylation of the 20 kDa myosin light chain. HA1077, a new type of vasodilator, inhibited both the cell rounding and the light chain phosphorylation in a concentration dependent manner. Since HA1077 inhibits myosin light chain kinase, in vitro, we propose that this vasodilator presumably inhibits cell rounding by limiting myosin light chain phosphorylation. PMID- 2222438 TI - Activation of GD3 synthase by sex steroid hormones in cultured rat hepatocytes. AB - The influence of sex steroid hormones on the activities of GM3 and GD3 synthases in isolated hepatocytes was studied. Progesterone (0.1 - 2.0 microM), beta estradiol (0.1 - 1 microM), and testosterone (0.1 - 1 microM) activate GD3 but not GM3 synthase when added directly to hepatocytes cultured in modified William's E medium. PMID- 2222439 TI - Conversion of big endothelin-1 by membrane-bound metalloendopeptidase in cultured bovine endothelial cells. AB - We propose a candidate for the "putative" endothelin (ET) converting enzyme in the cultured endothelial cells (ECs) of bovine carotid artery. The enzyme is membrane-bound, soluble in 0.5% Triton X-100, and capable of converting human big ET-1 to ET-1 by a specific cleavage between Trp21 and Val22. The conversion reached 90% after a 5-hr incubation in the presence of DFP, PCMS and pepstatin A, but it was inhibited by EDTA, omicron-phenanthroline or phosphoramidon. The enzyme is very sensitive to pH, and active only between pH 6.6 and pH 7.6. Conversion of big ET-3 by this enzyme was only 1/9 that of big ET-1. From these results, ET-1 converting enzyme in the bovine EC is most likely to be a membrane bound, neutral metalloendopeptidase, which is much less susceptible to big ET-3. PMID- 2222440 TI - Theoretical variation of the H alpha chemical shift in acetyl-glycyl-N methylamide and oligoglycines with molecular conformation and environment. AB - The sum of the magnetic anisotropy and polarization contributions to the magnetic shielding constants of the alpha protons is calculated as a function of the torsion angles about the NC alpha (phi) and C alpha C' (psi) bonds of the dipeptide. The results show that the polarization or electric field effect is several fold larger than the magnetic anisotropy contribution. The calculated variations are large enough to account for the spread of the values measured for these protons in peptides and proteins. The results obtained for polyglycine alpha helices and antiparallel beta sheets are discussed in relation with molecular conformation and environmental effects on the one hand and experimental data on the other. PMID- 2222441 TI - Catalase HPI influences membrane permeability in Escherichia coli following near UV stress. AB - The katG gene in Escherichia coli encodes catalase HPI, which is involved in membrane transport and protects the cell during oxidative stress. Hydrogen peroxide (H2O2) induces synthesis of HPI. We examined the role of HPI in membrane permeability (proline uptake) following exposure to near-ultraviolet radiation (NUV). We found that NUV resulted in the same type of induction as H2O2. KatG::Tn10 cells experienced a large drop in uptake after NUV exposure, and levels remained low following incubation. A strain carrying a katG+ plasmid, however, showed considerably less decrease in uptake after NUV, and uptake quickly resumed upon incubation. Further, in an srd mutant which lacks 4 thiouracil, NUV resulted in only a small drop in proline uptake, which was immediately resumed. PMID- 2222442 TI - The mast cell as an effector of connective tissue degradation: a study of matrix susceptibility to human mast cells. AB - The susceptibility of connective tissue elements to degradation by human mast cells was explored using purified mast cell tryptase and sonicated mast cell preparations. The R-22 strain of smooth muscle cells from rat heart was used for preparation in vitro of a labelled anchored matrix. Digestion of 11.9 +/- 1.2% (n = 5) of this matrix was observed after overnight incubation with the mast cell sonicates. Pretreatment of the sonicate with a tryptase inhibitor TLCK reduced the digestion by 42%. Digestion of 12 +/- 1% (n = 4) of the matrix was observed with purified tryptase. The susceptible substrate within this anchored insoluble matrix resided in the glycoprotein compartment as defined by enzymatic characterization of the residual matrix. Mast cells may play a role in mediating connective tissue degradation through the release of proteases specifically synthesized by this cell. PMID- 2222443 TI - Binding of human sex hormone-binding globulin-androgen complexes to the placental syncytiotrophoblast membrane. AB - We have found that human SHBG complexed with androgens binds specifically to the plasma membrane of human placental syncytiotrophoblast. Apparent equilibrium association constants were 5.3.10(11) M-1 for SHBG-testosterone complex and 1.1.10(11) M-1 for SHBG-5 alpha-dihydrotestosterone. Devoid of steroid, SHBG did not bind to the membrane. This suggests that the specific membrane binding of SHBG-androgen complexes is a step of the mechanism of androgen action on syncytiotrophoblast. PMID- 2222444 TI - Characterization of endothelin converting enzyme in rat lung. AB - An enzyme activity which converts human big endothelin (1-38) to endothelin (1 21) and a C-terminal fragment (CTF, 22-38) was identified in a plasma membrane fraction prepared from rat lung. The conversion activity was optimal at pH 4.0, was inhibited by Pepstatin-A (IC50 = 20 nM), but was not affected by TLCK, Aprotinin, PMSF, E-64, Bestatin, Phosphoramidon or Thiorphan at 40 microM. Metal ions activated the activity by 1.5 - 2.5 fold in the order of Mn+2 greater than Zn+2 = Ca+2 greater than Ba+2. These data suggest that a Pepstatin-A inhibitable, metal ion related aspartic protease may be involved in the conversion of big endothelin to endothelin in rat lung. PMID- 2222445 TI - The complete nucleotide sequence of the gene coding for botulinum type C1 toxin in the C-ST phage genome. AB - Two DNA fragments, 3 kbp and 7.8kbp, which encode the type C1 botulinum neurotoxin gene, were obtained from toxigenic bacteriophage DNA by treatment with a restriction enzyme. They were cloned into the plasmid vectors for nucleotide sequence determination. The nucleotide sequence contained a single open reading frame coding for 1,291 amino acids corresponding to a polypeptide with a molecular weight of 149,000. The amino acid sequence of the C1 toxin has a few regions highly homologous with tetanus toxin. PMID- 2222447 TI - Sequence similarities between tryptophan synthase beta subunit and other pyridoxal-phosphate-dependent enzymes. AB - On the basis of 8 tryptophan synthase beta subunits (EC 4.2.1.20) consensus patterns were constructed comprising two conserved motifs. Screening of the SWISSPROT protein sequence database with these patterns indicates similarities with O-acetylserine sulfhydrolases (EC 4.2.99.8), threonine synthases (EC 4.2.99.2), L- and D-serine dehydratases (EC 4.2.1.13/EC 4.2.1.14) and threonine dehydratases (EC 4.2.1.16). Using multiple alignment procedures the similar regions could be extended. In connection with their pyridoxal-phosphate-binding capacity and their positions in biochemical pathways evolutionary relationships among these enzymes are discussed. PMID- 2222446 TI - Allosteric control of quaternary states in E. coli aspartate transcarbamylase. AB - Changes in the molecular dimensions of ATCase in the unligated T-state are an increase of 0.4 A in the separation of catalytic trimers when ATP binds. When the R-state is produced by binding of phosphonoacetamide and malonate, addition of CTP or CTP + UTP decreases the separation of catalytic trimers by 0.5 A. In the unliganded Glu239----Gln mutant, in which the T-state is destabilized so that the enzyme exists in an intermediate quaternary state, ligation of ATP transforms the mutant enzyme to the R-state, whereas CTP converts this enzyme to the T-state. Thus, this mutant is much more sensitive to heterotropic allosteric control than is the native enzyme. In this communication we propose a preliminary model based on new crystallographic results that heterotropic regulation occurs partly through control of the quaternary structure by these effectors, thus regulating catalysis. PMID- 2222448 TI - Enhanced leukotriene C4 synthase activity in thioglycollate-elicited peritoneal macrophages. AB - The utilization of LTA4 by peritoneal macrophages (MO) obtained from untreated rats (control) as well as by those elicited from rats was investigated at designated intervals (on days 3, 7, and 14) following the intraperitoneal injection of thioglycollate (TG). On day 7 following the injection the elicited MO converted LTA4 to LTC4 at the highest rate while the resident MO showed the lowest rate. The conversion of LTA4 to LTC4 and LTB4 was next examined by using each MO lysate. The apparent LTC4 synthase activity was significantly higher in the MO lysate both on day 3 and day 7, with the latter being the highest value obtained. The GSH S-transferase activity in each lysate using as the substrate, DNCB was significantly lower on day 3 but significantly higher on day 7 as compared to control values. However, this elevated activity was less variable than that observed with LTC4 synthase. The possible implication for these observations is discussed. PMID- 2222449 TI - Inactivation of hepatocyte protein kinase C by carbon tetrachloride: involvement of drug's metabolic activation and prooxidant effect. AB - The involvement of CCl4 biotransformation mechanism in decreasing the Protein Kinase C activity has been analyzed in hepatocytes isolated from phenobarbital pretreated rats. A significant inhibition (55%) and an almost total disappearance (87%) of the enzyme activity were observed at 15 min and at 30 min incubation with CCl4, respectively. Cell preincubation with Trolox or desferrioxamine allowed a marked whilst not complete protection of both cytosolic and particulate Protein Kinase C activity. These results show that the CCl4 reactive metabolites play a primary role in hepatocyte Protein Kinase C impairment and suggest that besides lipid peroxidation other mechanisms -possibly a derangement of Ca2+ homeostasis- may be involved in this process. PMID- 2222450 TI - Stimulation of Mn-superoxide dismutase expression by tumor necrosis factor-alpha: quantitative determination of Mn-SOD protein levels in TNF-resistant and sensitive cells by ELISA. AB - Marked increase in protein levels of Mn-superoxide dismutase (Mn-SOD) was found in TNF-resistant cell lines after treatment with Tumor Necrosis Factor (TNF). No such increase was observed in Cu,Zn-superoxide dismutase (Cu, Zn-SOD) protein in either TNF-resistant or sensitive cells. These results support the data that the Mn-SOD is one of the rescue proteins required for resistance to TNF cytotoxicity in these cell lines (Wong et al., Cell 58, 923-931, 1990). Mn-SOD was also responsive to TNF stimulation in KURAMOCHI, a human ovarian adenocarcinoma cell line. This may explain our previous result that Mn-SOD protein is highly expressed in epithelial ovarian cancer (Ishikawa et al. Cancer Res. 50, 2538 2542, 1990). PMID- 2222451 TI - Polyethylene glycol modification of the monoclonal antibody A7 enhances its tumor localization. AB - The F(ab')2 fragment of murine monoclonal antibody A7 was covalently bonded to polyethylene glycol (PEG, molecular weight: 5000) and the conjugate was compared to the parent F(ab')2 fragment by in vitro and in vivo studies. PEG-conjugated antibody fragment retained its antigen-binding activity in a competitive radioimmunoassay. The conjugate had a longer half-life and showed increased accumulation in tumors. Although the tumor: blood ratio for parent F(ab')2 fragment was higher than that for the conjugate, it showed higher value than whole MAb A7. The tissue: blood ratios were kept low with the conjugate, indicating that the conjugate was uptaken to normal organ with lesser extent, as compared with parent F(ab')2 fragment. Our findings indicate that this PEG conjugated F(ab')2 fragment could be a promising carrier for use in targeting cancer chemotherapy. PMID- 2222452 TI - Altered methylation of versican proteoglycan gene in human colon carcinoma. AB - We show for the first time that DNA isolated from human colon carcinoma tissue exhibits a selective hypomethylation of versican gene, which encodes a large chondroitin sulfate proteoglycan. The degree of methylation of CpG sequences of versican gene locus, as determined by isoschizomeric endonucleases and Southern hybridization, is about three times lower than that found in either normal colon or ulcerative colitis tissues. Hypomethylation can be observed in both benign and malignant colonic neoplasms; however, there is no correlation with increased expression since versican mRNA levels do not significantly vary between normal and neoplastic tissues. We further show that versican gene locus from malignant tissue, but not from normal or ulcerative colitis tissues, contains Hind III hypersensitive sites which also comprise hypomethylated CpG sequences. Analysis of versican methylation status in colon carcinoma cells and benign mesenchymal cells derived from human colon suggests that the changes observed in vivo derive from demethylating events involving host stromal cells rather than tumor cells themselves. These findings demonstrate that changes in versican gene methylation are specific for colonic neoplasms, that these changes may precede malignant transformation, and that inflammation and tissue remodelling alone are not enough to generate these changes in proteoglycan gene methylation and nuclease hypersensitivity. PMID- 2222453 TI - The 108-kDA peptidylglycine alpha-amidating monooxygenase precursor contains two separable enzymatic activities involved in peptide amidation. AB - A 43-kDa protein factor that increases the ability of purified bovine peptidylglycine alpha-amidating monooxygenase (PAM)-A and -B to produce alpha amidated peptides at physiological pH was purified to homogeneity from bovine neurointermediate pituitary. At each step of the purification, the amount of activity correlated with the amount of protein detected on Western blots by antibody to bovine PAM(561-579). In the bovine neurointermediate pituitary the 108-kDa PAM precursor protein is cleaved to form a peptidylglycine alpha hydroxylating monooxygenase and a peptidyl-alpha-hydroxyglycine alpha-amidating lyase, which function sequentially in the 2-step formation of alpha-amidated peptides. PMID- 2222454 TI - Modulation of smooth muscle calponin by protein kinase C and calmodulin. AB - When smooth muscle calponin was incubated with protein kinase C, 1 mole of phosphate was incorporated per mole of calponin. The apparent Km value for calponin of the protein kinase was about 0.4 microM. The phosphorylation of calponin by protein kinase C was inhibited markedly by calmodulin in a calcium dependent manner. Kinetic analysis of calmodulin-induced inhibition of calponin phosphorylation by protein kinase C revealed that calmodulin inhibited the phosphorylation in a noncompetitive fashion with calponin and the determined Ki value was 0.4 microM. These results suggest that interaction of calmodulin with calponin may play a regulatory role in the phosphorylation by protein kinase C and smooth muscle contraction. PMID- 2222455 TI - Antagonistic effect of human alpha-CGRP [8-37] on the in vivo regional haemodynamic actions of human alpha-CGRP. AB - In conscious rats, infusion of human alpha-CGRP [8-37] (30 nmol/kg/min) caused small, reversible reductions in hindquarters flow and vascular conductance only, whereas at a dose of 300 nmol/kg/min there was a tachycardia and an increase in mean arterial blood pressure, together with renal, mesenteric and hindquarters vasoconstrictions. Human alpha-CGRP (0.03 nmol/kg/min) caused tachycardia, hypotension, and transient renal, but sustained hindquarters, vasodilatation; these changes were accompanied by mesenteric vasoconstriction. Infusion of human alpha-CGRP [8-37] (30 nmol/kg/min) during administration of human alpha-CGRP (0.03 nmol/kg/min) abolished the effects of the latter but these re-appeared when the human alpha-CGRP [8-37] infusion was stopped. This dose of human alpha-CGRP [8-37] did not affect cardiovascular responses to isoprenaline. These results indicate that human alpha-CGRP [8-37] is an effective antagonist of the cardiovascular actions of human alpha-CGRP in vivo. PMID- 2222456 TI - Evidence for protein kinase C independent activation of phospholipase D by phorbol esters in lymphocytes. AB - Recently it was reported that tumor-promoting phorbol esters stimulate the production of phosphatidylethanol (PEt) in lymphocytes through the activation of phospholipase D (PLD). However, it remains unclear whether this activation is mediated through protein kinase (PKC). The study reported here shows that tumor promoters 12-0-tetradecanoylphorbol-13-acetate (TPA), phorbol dibutyrate (PDBU), 12-deoxyphorbol-13-phenylacetate (DOPP), 12-deoxyphorbol-13-phenylacetate-20 acetate (DOPPA) and mezerin activated PLD, as measured by the formation of PEt, whereas Concanavalin A (ConA) had no effect. Inhibitors of PKC, sphingosine (2 x 10(-6) M - 5 x 10(-6) M), H-7, HA1004 (5 x 10(-7) - 5 x 10(-6) M) and K252a (1 x 10(-7) - 1 x 10(-6) M) failed to block the PEt synthesis induced by TPA. In fact, sphingosine increased it. Other PKC activators, 1-oleoyl-2-acetylglycerol (OAG) and dioctanoylglycerol (DiC8) had no effect on lymphocyte PLD activity. Analysis of the phospholipid contents after stimulation by TPA showed that only phosphatidylcholine (PC) was significantly decreased. Interestingly, TPA activated PLD in intact cells but not in lysates or subcellular fractions. These observations suggest that stimulation of PLD-catalyzed PEt synthesis by TPA is not solely mediated through PKC activation. PMID- 2222457 TI - Estradiol increases the secretion by MCF7 cells of several lysosomal pro-enzymes. AB - The synthesis and secretion of pro-cathepsin D is increased by estrogens in MCF7 cells. We quantified the effect of estradiol on other lysosomal enzymes in order to investigate the mechanism of this hypersecretion. Precursors of beta hexosaminidase, cathepsin B and beta-galactosidase, which are routed to lysosomes via the mannose-6-phosphate (Man-6-P) receptor, were secreted in much lower amounts than pro-cathepsin D, but their secretion was also increased by estradiol. The activity of acid phosphatase, which is routed to lysosomes via a different transmembrane mechanism, was not altered by estradiol. While estradiol stimulated gene expression of pro-cathepsin D, it had no effect on that of pro cathepsin B. We conclude that estradiol stimulates the secretion of several lysosomal pro-enzymes in MCF7 cells, suggesting that a general mechanism is responsible for this derouting rather than a specific alteration of cathepsin D structure. PMID- 2222458 TI - Isolation and sequencing of mouse angiogenin DNA. AB - The mouse genomic DNA for angiogenin, a potent blood vessel inducing protein, has been isolated from a bacteriophage library using the human angiogenin gene as a probe. The 1129 bp fragment contains 499 bp in the 5' flanking region, 192 bp in the 3' flanking region, and 438 bp coding for the mature protein (121 amino acids) and signal peptide (24 amino acids). Potential TATA box and AATAAA polyadenylation sequences are present, and a consensus sequence for an intron 3' boundary occurs 16 bp upstream of the Met-(24) codon, suggesting the presence of an intron in the 5' region. The protein sequence inferred from the DNA is 76% identical to that of human angiogenin, and matches the sequences obtained previously from tryptic peptides of a serum-derived mouse angiogenin. The critical catalytic residues of human angiogenin are conserved in the mouse protein, as are the six cysteines necessary for disulfide bond formation. PMID- 2222459 TI - Decreased heat shock response upon adipose differentiation of 3T3-L1 cells. AB - In order to gain a better understanding of the regulation of heat shock gene (hsp) expression in terminal cell differentiation, we evaluated the effects of heat shock on the synthesis of HSPs, the abundance of mRNAhsp, and the heat shock transcription factor (HSTF) DNA-binding activity in the 3T3-L1 fibroblasts and adipocytes. We showed that the heat shock (42 degrees C) induction of synthesis of HSPs was significantly greater in the undifferentiated fibroblast than the differentiated adipocyte cultures. In particular, the heat shock induced synthesis of HSP 72 was at least 10 times greater in the fibroblasts than in the adipocytes. Analysis of mRNA of hsp 89 alpha, hsp 89 beta, hsp 70, and hsp 25 by Northern blot hybridization showed that the expression of these mRNAs was very, if not strictly, dependent on heat shock of the cells; the abundance of these heat inducible mRNAs was significantly higher in fibroblasts than in adipocytes. Quantitation of the HSTF DNA-binding activity by gel retardation assay demonstrated a specific decrease in this activity in the differentiated cells. These results provide evidence of a decreased transcriptional activation of heat shock genes upon adipose cell differentiation. PMID- 2222460 TI - Plasma lipoproteins mediate platelet adhesion. AB - Platelet adhesion to VLDL, LDL, HDL, and to a mixture of purified apolipoproteins was examined. Platelets adhered to all the classes of lipoproteins tested. VLDL and the apolipoprotein mixture promoted the greatest degree of adhesion. Platelet adhesion was inhibited by addition of EDTA, RGD-containing peptides and anti GPIIb-IIIa, monoclonal antibodies. Platelets from patients with Glanzmann's Thrombasthenia which lack the GPIIb-IIIa receptor adhered to VLDL less than half as well as did normal platelets. These results demonstrate that the major circulating lipoproteins can mediate in vitro platelet adhesion and that this adhesion occurs via platelet integrin receptors. We postulate that lipoprotein mediated platelet adhesion may play an important role in the progression of atherosclerosis. PMID- 2222461 TI - Heat-induced preferential synthesis and redistribution of HSP 70 and 28 families in Chinese hamster ovary cells. AB - We observed that members of two HSP families (70 and 28 kDa) preferentially redistributed into the nucleus after heating at 45.5 degrees C for 10 min. The rates of synthesis and redistribution of these proteins were different for each member of HSP families during incubation period at 37 degrees C after heat shock. The maximum rates of synthesis of HSP 70 and HSP 28 families, except HSP 28c, were 6-9 hr after heat shock, whereas the maximum rates of redistribution were 3 6 hr after heat shock. These results suggest that the rates of redistribution of these proteins may be dependent on the amount of intracellular proteins as well as the alteration of binding affinity of nucleoproteins following heat shock. PMID- 2222462 TI - Expression of constitutive and inducible HSP70 and HSP47 is enhanced in cells persistently spread on OPN1 or collagen. AB - Cells persistently spread on OPN or collagen survive heat shock better than cells transiently spread on fibronectin or tissue culture plates. Thus, a central question is whether constitutively or inducible stress proteins are enhanced in cells grown on adhesive proteins that maintain a persistent spread cell shape. Levels of Hsp 72,73, and colligin/Hsp47 were determined by Western blot analyses. The inducible Hsp 72 was prominently expressed following heat shock in cells grown on OPN or collagen, but not in cells plated on fibronectin coated substratum or on tissue culture plates. Colligin/Hsp 47 and Hsp 73 manifested a similar pattern of expression indicating that these adhesive attachment proteins accommodate cell function through organization of cell architecture. PMID- 2222463 TI - L-glutamine inhibits the release of endothelium-derived relaxing factor from the rabbit aorta. AB - The present study investigates the effect of the amino acid L-glutamine (L-Gln) on the release of endothelium-derived relaxing factor (EDRF) from the luminally perfused rabbit aorta and on endothelium-dependent relaxations of rabbit aortic strips. L-Gln (200 microM) had no effect on the acetylcholine (Ach)-induced release of EDRF from freshly prepared aortic tissues. The concentration of L arginine (L-Arg) in endothelial cells isolated from these aortae was approximately 4 mM, as determined by HPLC analysis. After an initial equilibration period of 2 h and two consecutive infusions of Ach (55 microM for 15 min) at 2 and 3 h, L-Arg levels fell by 62 +/- 14% (n = 4). Under these conditions, L-Gln (200 microM) but not D-Gln (200 microM) inhibited the release of EDRF by 50 +/- 4% (n = 7). This effect of L-Gln was partially reversed by infusions of L-Arg (500 microM) but not D-Arg (500 microM). L-Gln (200 microM) but not D-Gln (200 microM) potentiated the inhibitory effect of N omega-nitro-L arginine (30 microM), an inhibitor of EDRF biosynthesis, on Ach-induced relaxations of rabbit aortic strips, whereas L-Gln alone had no effect. Thus, L Gln inhibits the release of EDRF from intact blood vessels presumably by interfering with the generation of L-Arg by the endothelium. PMID- 2222464 TI - Human colony stimulating factor-1 receptor activates the C-raf-1 proto-oncogene kinase. AB - The proto-oncogene c-raf-1 encodes a 74 kD serine/threonine kinase. Recently, it has been shown that Raf kinase activity is stimulated by platelet derived growth factor (PDGF) treatment of receptor bearing cells, and that p74 is a direct substrate for PDGF receptor. CSF-1 treatment of BeWo cells, a human choriocarcinoma cell line, and mouse NIH 3T3 cells expressing a transfected human CSF-1 receptor cDNA, was associated with a 3-4 fold increase in phosphorylation of a 74 kD protein immunoprecipitated with affinity purified Raf-1 antibody. The kinase activity of p74 was increased 2-3 fold against two exogenous substrates following CSF-1 treatment of the transfected cells. These observations suggest that Raf-1 protein is a downstream second messenger molecule in CSF-1 mediated signal transduction. PMID- 2222465 TI - N-glycosylated and unglycosylated forms of caprine trophoblast protein-1 are secreted by preimplantation goat conceptuses. AB - Goat conceptuses secrete caprine trophoblast protein-1 (cTP-1) which is related antigenically to the abundant embryonic interferon-alpha II of sheep and cattle. Antiserum to ovine and bovine TP-1s immunoprecipitated three molecular weight classes (23,000, 21,000 and 17,000, each with two isotypes) of cTP-1 from goat conceptus culture medium. Cultures which contained tunicamycin resulted in a shift in the Mr = 23,000 and Mr = 21,000 forms to a Mr of 17,000. The Mr = 23,000 and 21,000 forms, but not the Mr = 17,000 form, bound to Concanaval in A Sepharose and were eluted under conditions selective for glycoproteins bearing complex-type oligosaccharide(s). Thus cTP-1 is a mixture of glycosylated and unglycosylated polypeptides. PMID- 2222466 TI - Chromosomal assignment of the human homologue encoding SGP-2. AB - Although originally characterized as a constitutively expressed gene product in mammalian Sertoli cells, sulfated glycoprotein-2 (SGP-2) has gained widespread attention due to its remarkably rapid and sizable induction in numerous types of mammalian cells undergoing apoptosis, or programmed death. In order to identify the chromosomal assignment for the human homologue of SGP-2, we performed Southern blot analysis of Bgl II restricted genomic DNA extracted from a panel of cloned hamster-human hybrid cell lines and screened for the presence of restriction fragments homologous to SGP-2. The results of this analysis indicate that the human homologue of SGP-2 resides on chromosome 8. PMID- 2222467 TI - Special considerations in the purification of the GM3 ganglioside forming enzyme, CMP-sialic acid:lactosylceramide alpha 2-3 sialyltransferase (SAT-1): solubilization of SAT-1 with lauryldimethylamine oxide. AB - Lauryldimethylamine oxide (LDAO) was employed in the purification of the GM3 ganglioside forming enzyme, CMP-sialic acid:lactosylceramide alpha 2-3 sialyltransferase (SAT-1) (4). This detergent has advantages over the typically employed Triton detergents in the solubilization and stabilization of this sialyltransferase. Crude protein fractions solubilized from rat liver Golgi by several such detergents are very similar in composition as determined by two dimensional gel electrophoresis. However, LDAO appears to activate and stabilize SAT-1 activity. It is possible that SAT-1 activation involves the structurally similar hydrophobic moieties and quaternary amino groups of LDAO and phosphatidylcholine. PMID- 2222468 TI - Interaction between corticosteroid binding globulin and activated leukocytes in vitro. AB - The interaction between human corticosteroid binding globulin and activated leukocytes is restricted to the granulocyte population, and is characterized by specific proteolytic cleavage of corticosteroid binding globulin which markedly reduces its steroid binding activity. A direct interaction between corticosteroid binding globulin and the activated cells appears to enhance this event, and does not involve cellular internalization of corticosteroid binding globulin or its proteolytic degradation products, which resemble those obtained after incubation of corticosteroid binding globulin with neutrophil elastase. These data suggest that corticosteroid binding globulin interacts with elastase on the surface of activated neutrophils, and may promote glucocorticoid delivery to these cells during inflammation. PMID- 2222469 TI - Endogenous digitalis-like factor as a stimulator of endothelin secretion from endothelial cells. AB - Effects of human urine-derived endogenous digitalis-like factor (EDLF) and ouabain on endothelin (ET) secretion were examined in cultured endothelial cells. ET was secreted in a linear fashion over 5 hours from bovine pulmonary artery endothelium into serum-free medium. EDLF stimulated ET secretion in a dose dependent manner. In contrast, ouabain did not affect ET secretion at the concentration of 10(-9)-10(-5) M. These results indicate that human urine-derived EDLF is distinct from plant-derived ouabain and act as a stimulator of ET secretion by endothelial cells. PMID- 2222470 TI - Thylakoid-bound chloroplast DNA from spinach is enriched for replication forks. AB - Chloroplast DNA is bound to the thylakoids of spinach chloroplasts. To examine a possible role for thylakoid-bound DNA in chloroplast DNA replication, vesicles formed by treating chloroplasts in 3.5 mM MgCl2 were used. Chloroplast DNA fragments are bound to the surface of these vesicles. Chloroplast DNA isolated from vesicles that had been first treated with Eco R1 contained 10% of branched fragments whereas chloroplast DNA isolated from intact chloroplasts and treated with Eco R1 contained 2% of branched fragments. This result is consistent with the growing replication fork of chloroplast DNA being associated with the chloroplast internal membrane system. Branched fragments from the chloroplast DNA digested with Eco R1 prior to the isolation from the vesicle contained fragments of unequal length. Membrane binding in chloroplasts may have a similar role in DNA replication as it does in bacteria. PMID- 2222471 TI - Direct visualization of affected collagen molecules synthesized by cultured fibroblasts from an osteogenesis imperfecta patient. AB - Human skin fibroblasts obtained from normal controls and a patient with osteogenesis imperfecta were cultured in the presence of ascorbic acid 2 phosphate, a long-acting vitamin C derivative. Crude collagen samples extracted from the cell layer were made to form lateral aggregates of collagen molecules, segment-long-spacing crystallites. Under the electron microscope, normal and abnormal crystallites of type I collagen were identified with the patient's collagen. While the carboxyl-terminal half of the abnormal crystallite was tightly packed, the amino-terminal half was loose and spreading, indicating the site of abnormality in the amino-terminal half of one of type I collagen alpha chains. The method is simple and useful to detect abnormal collagen and to predict the site of mutation. PMID- 2222472 TI - Message amplification phenotyping of an inherited delta-aminolevulinate dehydratase deficiency in a family with acute hepatic porphyria. AB - The molecular basis of the enzymatic defect responsible for acute hepatic porphyria due to delta-aminolevulinate dehydratase (ALAD) deficiency was investigated in a family including a proband with the acute disease. In order to delineate the mutation in the proband, cDNA for deficient ALAD was synthesized from the proband's cells. The ALAD phenotype was studied by message amplification phenotyping with total RNA extracted from lymphoblastoid cells of the proband and his family members. Two independent mutant alleles of ALAD were identified in the proband's cells. One mutant allele was shown to result in an amino acid substitution at residue 274 (Ala274----Thr). Message amplification phenotyping studies have also permitted us to define the ALAD phenotype of each subject in the family. This is the first mutation to be recognized in the human ALAD gene. PMID- 2222474 TI - Estrous cycle dependent regulation of peptidylarginine deiminase transcripts in female rat pituitary. AB - Northern blot hybridization demonstrated 4.5-5.0 kilobase peptidylarginine deiminase mRNA in poly (A)+ RNA-enriched fractions of both male and female pituitaries. Dot blot analysis of total RNA fractions showed more than 50-fold sex difference in the mRNA content. The female pituitary mRNA content showed at least a 50-fold variation during the estrous cycle characterized by elevation at diestrus and proestrus followed by a rapid decline at estrus. The data were discussed in comparison with the sex difference and estrous cycle dependence of the pituitary enzyme content reported previously. PMID- 2222473 TI - Efflux of bis-carboxyethyl-carboxyfluorescein (BCECF) by a novel ATP-dependent transport mechanism in epithelial cells. AB - The efflux of the intracellular pH fluorochrome 2',7'-bis(2-carboxyethyl)-5(6) carboxyfluorescein (BCECF) was quantified in four cultured epithelial cell lines; HCT-8, T84, HGT-1 and MDCK. BCECF efflux was time-dependent, and after 5 h 45-91% of the initial BCECF loaded was extracellular, efflux being greatest in MDCK cells. Depletion of cellular ATP approximately halved BCECF efflux. BCECF efflux was inhibited by indomethacin, vinblastine and verapamil, but not by nifedipine or reserpine. Certain features of BCECF efflux resemble drug efflux in multidrug resistant cells, but inhibition of efflux displays a distinct pharmacological profile suggesting BCECF is a substrate for a novel ATP-dependent transport system. PMID- 2222475 TI - Electro-permeabilization of cell membranes: effect of the resting membrane potential. AB - Electric field induced permeabilization of cell membranes is an important technique for gene transfection and cell hybridization. Mechanistic studies of this process revealed that the uptake of fluorescent indicator by plant protoplasts occurs predominantly on the hemisphere facing the positive electrode, while in erythrocyte ghosts the probes exit through the hemisphere facing the negative electrode. To reconcile these observations symmetrical pore formation and a mechanism of molecular exchange by electroosmosis has been proposed. In light of these controversial observations, we conducted a systematic study of electroporation of NIH3T3 cells with varying electric field strength, waveform and frequency. Our data revealed that (i) symmetrical permeabilization of the cell membrane occurs only with bipolar a.c. fields. (ii) When a critical membrane breakdown potential, Vc, is applied using either an unipolar a.c. fields or a single d.c. square pulse, the cell membrane becomes permeabilized only at the hemisphere facing the positive electrode. (iii) When the pulse-induced membrane potential, Vm, is approximately equal to or larger than the intrinsic membrane potential (i.e. using d.c. or unipolar a.c. field), asymmetric permeabilization was observed with the hemisphere facing the positive electrode being most permeable. (iv) The rate of fluorescent indicator uptake is dependent on the concentration of the indicator. These results indicate that electro permeabilization of cell membranes is affected by its resting potential and that electroosmosis is not the dominant mechanism for the cellular uptake of foreign molecules in electroporation. PMID- 2222476 TI - Inhibition of human immunodeficiency virus type 1 replication by phosphonoformate esters of 3'-azido-3'-deoxythymidine. AB - The water-soluble ammonium salt of 3'-azido-5'-(O-ethoxycarbonylphosphinyl)-3' deoxythymidine (ECP-AZT), the prototype of a novel class of compounds incorporating two active antiretroviral agents, in this case 3'-azido-3' deoxythymidine (AZT) and phosphonoformic acid (PFA), within the same structure, was synthesized and tested as an inhibitor of the replication of human immunodeficiency virus type 1 (HIV-1) in Jurkat cells, a CD4+ human T-lymphocyte cell line. The corresponding 5'-(O-methoxycarbonylphosphinyl) derivative (MCP AZT) was also prepared. The rationale for the synthesis of ECP-AZT and MCP-AZT was that they may be cleaved intracellularly to AZT and PFA via hydrolysis of the phosphate ester bond or to AZT 5'-monophosphate by oxidative cleavage of the carbon-phosphorus bond. ECP-AZT was found to block viral replication at a 50% inhibitory concentration (IC50) of ca. 10(-6) M as measured by reverse transcriptase (RT) activity in supernatants from cultures of infected cells. Little or no inhibition of cell growth was observed at this concentration, and there was less than 20% inhibition of cell growth at 10(-4) M. AZT itself was a more potent inhibitor of HIV-1 replication than ECP-AZT, but was also more cytotoxic. The antiviral selectivity of ECP-AZT, defined as the ratio IC50 (virus inhibition)/IC50(cell growth inhibition), was in the range considered to be therapeutic for anti-AIDS nucleosides. PMID- 2222477 TI - Metabolic correction of fucosidosis lymphoid cells by galaptin-alpha-L-fucosidase conjugates. AB - To determine if isolated galaptin, an endogenous galactoside-binding lectin, could serve as a transport vehicle of therapeutic agents to cells, galaptin and alpha-L-fucosidase were coupled using glutaraldehyde. The conjugates were incubated with alpha-L-fucosidase-deficient, EBV-immortalized lymphoid cells from a fucosidosis patient. Conjugates were effectively bound and internalized by the cells in a lactose inhibitable manner. Internalization of conjugate resulted in the reduced accumulation of alpha-L-fucosyl-N-acetylglucosaminylasparagine, a glycopeptide that accumulates in cells of fucosidosis patients, to levels found in lymphoid cells from a healthy individual. Thus, galaptin-alpha-L-fucosidase conjugates may be useful for enzyme replacement therapy of fucosidosis. The concept of using galaptin as a transport vehicle may be applied to the delivery of other compounds to cells bearing galaptin receptors. PMID- 2222478 TI - Release of T-antigen, a carcinoma marker from native human cells, by endo-alpha-N acetylgalactosaminidase of Alcaligenes sp. AB - The endo-alpha-N-acetylgalactosaminidase from Alcaligenes sp. could release T antigen (Ga1 beta 1----3GalNAc), a carcinoma-associated marker from asialo glycophorin and human cells. The released T-antigen from human asialo erythrocytes was determined by thin layer chromatography and gas liquid chromatography. The released T-antigen from human gastric carcinoma cell Kato III was identified by high performance liquid chromatographies with a reverse-phase column and a size fractionation column. Released T-antigen could be analyzed quantitatively by a sensitive method including pyridylamino derivatization and following high performance liquid chromatography. This suggests that the enzyme is useful for detection and determination of T-antigen from cells. PMID- 2222479 TI - An active site of growth hormone for eliciting the differentiation of preadipose 3T3-F442A cells to adipose cells. AB - In order to elucidate the active sites of growth hormone for eliciting the differentiation of preadipose 3T3-F442A cells to adipocytes, four artificial mutant variants of human growth hormone (hGH) modified in the loop region of amino acid residues 54-74 were prepared in Escherichia coli by site-directed mutagenesis. Although the P59A (replacement of Pro59 with Ala) variant retained almost the same biological- and receptor binding-activity as hGH, the P61A (replacement of Pro61 with Ala) and the P59A-P61A (replacement of both Pro59 and Pro61 with Ala) both exhibited about half the activity, and the delta (62-67) variant (deletion of the residues 62-67) exhibited only about 0.1% the activity of those of intact hGH. The results suggest that Pro61 may be involved in formation of the active conformation of hGH, but Pro59 may not, and that the amino acid residues around 62-67 may be critical for the specific biological features of hGH. PMID- 2222480 TI - Peroxisomal disorders: complementation analysis using beta-oxidation of very long chain fatty acids. AB - Complementation studies, using fused cell lines from patients with peroxisomal disorders, have shown correction of defective plasmalogen synthesis and phytanic acid oxidation as well as an increase in the number of peroxisomes. At least six complementation groups have been reported. We demonstrate here that complementing cell lines also acquire the ability to oxidize very long chain fatty acids (VLCFA), and that complementation groups defined with this technique are identical to those reported previously when plasmalogen synthesis was used as the criterion for complementation. This VLCFA complementation technique is of particular value in the study of patients in whom defective VLCFA is the only or major enzymatic defect, and we show complementation between cell lines from two patients each with an isolated defect in one of the peroxisomal fatty acid beta oxidation enzymes. PMID- 2222481 TI - Changes in intracellular calcium of porcine sperm during in vitro incubation with seminal plasma and a capacitating medium. AB - The intracellular free Ca2+ concentration in ejaculated, porcine sperm was determined with a fluorescent, Ca2(+)-specific probe, Fura 2. Following suspension of sperm in a medium capable of sustaining capacitation and the acrosome reaction, the intracellular [Ca2+] increased from an initial value of about 75 nM to a peak value of 130 nM, after about 4 to 5 h of incubation. Within this period of time, a peak value of 246 nM was attained when sperm was incubated in seminal plasma. Ca2+ uptake is presumably not associated with membrane potential-dependent channels. The results indicate that a pronounced increase in intracellular free Ca2+ occurs towards the end of the incubation period when rather synchronous acrosome reactions take place in the sperm population, either in capacitating medium or in seminal plasma. PMID- 2222482 TI - Insulin-like growth factor 1 supports embryonic nerve cell survival. AB - Insulin-like growth factor 1 (IGF-1) is shown to support the long term survival of embryonic chicken central nervous system neurons cultured in a defined medium. This trophic activity for IGF-1 was discovered as the result of its presence as a contaminant in bovine serum albumin, a reagent frequently used in primary cultures of neuronal tissue. The observation that IGF-1 has cell survival activity may explain the high level of IGF-1 receptors found in embryonic brain. PMID- 2222483 TI - Extracellular depolymerization of hyaluronic acid in cultured human skin fibroblasts. AB - The chain length of [3H]hyaluronic acid synthesized by cultivating human skin fibroblasts in the presence of [3H]glucosamine was investigated. [3H]Hyaluronic acid obtained from the matrix fraction was excluded from a Sepharose CL-2B column irrespective of the incubation period, whereas that from the medium was depolymerized into a constant chain length (Mr = 40,000). The reducing and non reducing terminals of the depolymerized hyaluronic acid were N-acetylglucosamine and glucuronic acid, respectively. Prolonged incubation produced no oligosaccharides as shown by examination of hyaluronidase digests, suggesting the presence of a novel endo-beta-N-acetylglucosaminidase in cultured human skin fibroblasts. PMID- 2222485 TI - Protein oxidation and myelinolysis occur in brain following rapid correction of hyponatremia. AB - Myelinolysis occurs following rapid correction of hyponatremia in both humans and experimental animals. Although the mechanism of this effect at present is unknown, we have examined the possibility that a rapid rise in serum sodium following hyponatremia potentiates an oxidative stress and results in the oxidation of cellular proteins. In these studies, rats treated with 1 M NaCl following 3 days of vasopressin-induced hyponatremia exhibited myelinolysis in the corpus striatum and thalamus as well as significant increases in soluble oxidized proteins in the brain. These changes did not occur in rats treated with 0.155 M (0.9%) NaCl following 3 days of hyponatremia. PMID- 2222484 TI - The strong hepatocarcinogenicity of the electrophilic and mutagenic metabolite 6 sulfooxymethylbenzo[a]pyrene and its formation of benzylic DNA adducts in the livers of infant male B6C3F1 mice. AB - 6-Hydroxymethylbenzo[a]pyrene was activated to an electrophilic and mutagenic sulfuric acid ester metabolite by rat and mouse liver sulfotransferase activity. The intrinsic mutagenicity of this reactive ester, 6 sulfooxymethylbenzo[a]pyrene, was inhibited by glutathione and glutathione S transferase. A single i.p. dose of 2.5 nmol/g body wt of 6 sulfooxymethylbenzo[a]pyrene in infant male B6C3F1 mice induced liver tumors in 35 of 36 mice at 10 months with an average multiplicity of 4.4. A comparable dose of the parent hydrocarbon, 6-hydroxymethylbenzo[a]pyrene, was only a tenth as active. The electrophilic sulfuric acid ester produced high levels of benzylic DNA adducts in the livers of these mice that accounted for about 80% of the total DNA adducts. These results strongly suggest that this sulfuric acid ester is an important ultimate electrophilic and carcinogenic metabolite in carcinogenesis by 6-hydroxymethylbenzo[a]pyrene and possibly even by 6-methylbenzo[a]pyrene and benzo[a]pyrene in mouse liver. PMID- 2222486 TI - Oxidative C4-demethylation of 24-methylene cycloartanol by a cyanide-sensitive enzymatic system from higher plant microsomes. AB - Microsomes isolated from corn embryos (Zea mays) were shown to catalyse the C-4 monodemethylation of 28-[3H],24-methylene cycloartanol 1, leading to the corresponding 4 alpha-methyl sterol, cycloeucalenol 5. An enzymatic assay has been developed for the 4,4-dimethyl sterol 4-demethylase in higher plants. The demethylation process was shown to involve a 4-methyl, 4-hydroxymethyl derivative 2 which can be considered as the immediate metabolite of 1 by the 4-methyl oxidase. Compound 2 is further metabolized into 5 through a 4-methyl-4-carboxylic acid 3 and a 3-keto-4 alpha-methyl intermediate 4 which were identified. The conversion of 1 into 5 requires NADPH and molecular oxygen. The initial oxidative step was strictly dependent upon molecular oxygen, NADPH or NADH, and strongly inhibited by cyanide, whereas the overall process was completely insensitive to CO and to specific inhibitors of cytochrome P-450. It is concluded that in Zea mays microsomes, the C-4 demethylation of 1 results from a multistep process involving a terminal oxygenation system sensitive to cyanide which is distinct from cytochrome P-450 and in particular from that involved in the 14 alpha demethylation of obtusifoliol. PMID- 2222487 TI - Presence of a plant-like glyoxalase II in Candida albicans. AB - Glyoxalase II from Candida albicans was purified by affinity chromatography on S carbobenzoxyglutathione-Affi Gel 10. The enzyme was characterized and compared with the glyoxalases II from animal and plant sources. The relative molecular mass is 29 kDa, and the isoelectric point (pI) is 6.0. The acidic pI value appears to be typical for plant glyoxalase II, in contrast to the uniformly basic glyoxalase II pI values from animals. S-D-Lactoylglutathione and S acetoacetylglutathione are the best substrates, and S-carbobenzoxyglutathione is the best inhibitor of the yeast enzyme. Glutathione derivatives with a thioether bond are not inhibitory. Glyoxalase II from Candida albicans is compared either with animal and plant enzymes. PMID- 2222488 TI - Relative contribution of glycogenolysis and gluconeogenesis to basal, glucagon- and nerve stimulation-dependent glucose output in the perfused liver from fed and fasted rats. AB - The relative contribution to basal, glucagon- and nerve stimulation-enhanced glucose output of glycogenolysis (glucose output in the presence of the gluconeogenic inhibitor mercaptopicolinate) and gluconeogenesis (difference in glucose output in the absence and presence of the inhibitor) was investigated in perfused livers from fed rats with high and from fasted animals with low levels of glycogen. 1) Basal glucose output in both states was due only to gluconeogenesis. 2) Glucagon-enhanced glucose output was due about equally to glycogenolysis and gluconeogenesis in the fed state, but predominantly to gluconeogenesis (80%) in the fasted state. 3) Nerve stimulation-increased glucose output was due mainly to glycogenolysis (65%) in the fed state and about equally to both processes in the fasted state. The results suggest that under basal conditions of normal demands the liver supplies glucose only via gluconeogenesis and thus spares its glycogen stores, and that in situations of enhanced demands signalled by an increase in glucagon or sympathetic tone the liver liberates glucose mainly via glycogenolysis. PMID- 2222489 TI - Conversion of rat urinary prokallikrein to its active form. AB - A peptide derived from rat urinary prokallikrein by trypsin treatment comprised 7 amino acids, the sequence (Ala-Pro-Pro-Val-Gln-Ser-Arg) of which was identical with that of the N-terminal region in prokallikrein. Thus, with trypsin treatment, rat urinary prokallikrein is converted to the active form with the release of the N-terminal propeptide consisting of 7 amino acids. An Arg-1-Val+1 bond in the prokallikrein was found to be the site of proteolytic cleavage of the propeptide. PMID- 2222491 TI - Kinetic and molecular parameters of human hepatic porphobilinogen deaminase. AB - A basal level of human liver porphobilinogen deaminase of 3.66 units/g wet weight was found in adult tissue. Activity in neonatal liver was at least three fold higher. Physico-chemical studies revealed that the enzyme has the approximate form of a symmetrical molecule and exhibits hyperbolic kinetics with a Km value of 3.6 microM at pH 7.6. Two ionizable groups with pK values of 7.35 and 8.90 are prominent for catalysis. A set of pI (5.8-4.9) were observed under different conditions. Results demonstrate the existence of a single protein differentially charged with multiple molecular forms in adult liver. PMID- 2222490 TI - Isolation of cyclo(His-Pro)-like immunoreactivity from human urine and demonstration of its immunologic, pharmacologic, and physico-chemical identity with the synthetic peptide. AB - Measurements of cyclo(His-Pro) levels in human urine were carried out by specific radioimmunoassay. Cyclo(His-Pro)-like immunoreactivity in Human urine was found to be immunologically, pharmacologically, and physico-chemically identical to that of synthetic cyclo(His-Pro). The concentration of urinary cyclo(His-Pro) in 24-h collection was 1133.8 +/- 122.5 nmol/L, with a range of 606 to 1865 nmol/L. The daily excretion rate of cyclo(His-Pro) was 1812 +/- 248 nmol cyclo(His-Pro)/g creatinine, or 1814 +/- 199 nmol cyclo(His-Pro/day. PMID- 2222492 TI - Transcriptional regulation of messenger RNA for ferritin heavy chain by thyrotropin. AB - Thyrotropin increased the steady state levels of ferritin heavy chain messenger RNA in cultured Fisher rat thyroid (FRTL5) cells by about 2.5-fold. Thyrotropin also stimulated the transcription rate of ferritin H gene determined by "nuclear run-on" assay by roughly the same extent as mRNA levels. Thyrotropin showed no effect on the stability of the ferritin heavy chain mRNA, which was suggested using actinomycin D. The results suggest that thyrotropin increases ferritin heavy chain mRNA expression in FRTL5 cells by affecting the step of transcription. PMID- 2222493 TI - Trypanosoma cruzi histones. Further characterization and comparison with higher eukaryotes. AB - Histones extracted from T. cruzi chromatin were analyzed in three electrophoretic systems. Our results show that a basic protein with some properties similar to those of histone H1 from higher eukaryotes is present in T. cruzi. However this protein presents different electrophoretic mobilities than H1 histone from higher eukaryotes in all three electrophoretic systems tested. Considering the marked differences observed in the electrophoretic mobilities of T. cruzi histones as compared with those from higher eukaryotes, it is proposed that histones are conservative proteins primarily with regard to their function. PMID- 2222494 TI - Partial amino acid sequence of osteocalcin from an extinct species of ratite bird. AB - Osteocalcin the major gamma carboxyglutamic acid containing protein of vertebrate bone has been purified from the bones of a specimen of Pachyornis elephantopus, a species of the extinct class of New Zealand ratite birds, the moas. The sequence of the N-terminal region of moa osteocalcin was determined using gas phase N terminal sequencing. The N-terminal sequences of the ostrich and rhea osteocalcins were also determined. Alignment of the N-terminal sequence of osteocalcin from the extinct moa against the osteocalcins of the extant ostrich, rhea and emu reveals the homology amongst the ratite species is greater than the homology with the chicken osteocalcin. PMID- 2222497 TI - Circadian changes in glycogen content in rat interscapular brown adipose tissue: effect of cold exposure and food deprivation. AB - The effects of food deprivation and cold exposure on brown adipose tissue (BAT) glycogen and lipid levels during the circadian cycle were studied. BAT glycogen levels in control animals followed a definite circadian cycle, showing an increase during the light period. In cold-exposed animals the pattern was different, with minimal values at the beginning of the dark period. Food deprivation caused a decrease in BAT glycogen concentration only after 48-hours. In contrast to the control animals, where BAT and liver showed a different glycogen pattern, in the cold exposed group the observed changes were similar. During cold exposure, lipid stores in BAT were decreased. The results obtained in this work highlight with the important role of glycogen and lipid stores in BAT thermogenesis. PMID- 2222495 TI - Glycogen biogenesis in the adipocyte and mammary adenocarcinoma and the influence of insulin. AB - 3T3 LI P-3 adipocytes and a rat mammary carcinoma each contain a protein (or proteins) of Mr 400 kDa approx. that undergoes glucosylation when incubated with UDPglucose and Mn2+. In each case, the product of glucosylation is a protein bound maltosaccharide containing up to 14 glucose residues, and therefore capable of priming glycogen synthesis. The proteins bear a formal similarity to the self glucosylating protein of Mr 37 kDa that primes muscle glycogen synthesis, but do not cross-react with an antibody that cross-reacts with the muscle protein. The extent of protein glucosylation in the adipocyte is rapidly and markedly stimulated when the cells are bathed in insulin, suggesting that this initial step in glycogen biogenesis, protein glucosylation, is under the influence of the hormone. PMID- 2222496 TI - Stimulation of protein synthesis by a 34 KD DNA-binding protein from human placenta. AB - A 34 KD DNA-binding protein fraction from human placenta stimulated endogenous protein synthesis in rabbit reticulocyte and wheat-germ cell-free systems. Though the synthesis of several proteins were stimulated by the 34 KD protein, a dose dependent increase of two polypeptides of molecular weights 42,000 and 51,000 were distinctly observed in reticulocyte lysates. The synthesis of the major protein (beta-globin) was not affected by the 34 KD protein. In both hemin supplemented and unsupplemented lysates, the ability of 34 KD protein to stimulate the synthesis of high molecular weight (HMW) proteins was drastically reduced by Mg++ and not by dsRNA. PMID- 2222498 TI - Sucralfate protection of gastric mucosa against alcohol-induced injury: a phosphoinositide mediated process. AB - The mechanism of protection by sucralfate against gastric mucosal injury induced by ethanol was investigated. The experiments in vivo were conducted with groups of rats with and without indomethacin pretreatment, and the animals received sucralfate followed by ethanol. In the in vitro experiments, gastric mucosa was cultured in the presence of sucralfate, ethanol, or both. The in vivo experiments revealed that ethanol caused extensive gastric hemorrhagic lesions which were significantly reduced following sucralfate pretreatment and that this effect of sucralfate was not prevented by indomethacin. The data with gastric mucosal culture demonstrated that ethanol caused a 24% decrease in mucin synthesis, while mucin synthesis in the presence of sucralfate increased by 32%. This increase was accompanied by the enhanced metabolism of mucosal phosphoinositides, as reflected by a 22% decrease in PI, 1,2-fold increase in IP1 and 3.4-fold increase in IP3. In contrast, ethanol, caused 1.5-fold increase in IP1 and PIP2, and 35% decrease in PIP, 47% decrease in IP2 and 38% decrease in IP3. However, when the mucosal culture was carried out in the presence of both sucralfate and ethanol, the detrimental changes evoked by ethanol in mucin synthesis were prevented. The results suggest that the mucosal protective action of sucralfate involves the metabolism of phosphoinositide-derived messenger molecules. PMID- 2222499 TI - Proposal of leukotoxin, 9,10-epoxy-12-octadecenoate, as a burn toxin. AB - It is postulated that toxic substances (burn toxin) synthesized in burned skin are transferred into general circulation and cause multiple organ failure. We found a highly cytotoxic substance, leukotoxin, a linoleate epoxide, exists in burned skin. Leukotoxin, as the name indicates, was synthesized by leukocytes from linoleate as a substrate. The aim of this study is to evaluate the possibility of leukotoxin as a burn toxin. We studied plasma leukotoxin level of four patients with extensive burns (over 50% of body surface area) and examined coagulation studies in these patients. We detected considerable amounts of leukotoxin (11.4 nmol/ml-37.0 nmol/ml) in all patients. Leukotoxin was not detected in the control subjects. Pulmonary edema, cardiac failure, and coagulation abnormalities were found in these patients. Exogeneously administered leukotoxin induced similar pathological conditions in experimental animals to those observed in patients with extensive burns. Hence, it is concluded that leukotoxin is a responsible substance as a burn toxin. PMID- 2222500 TI - Actinomycin D suppresses hydrocortisone-induced changes in distribution and sialylation of brush-border enzymes in jejunal villi and crypts. AB - To investigate the regulatory role of hydrocortisone in the postnatal decline of sialylation of intestinal brush-border hydrolases, we applied actinomycin D, the well-known inhibitor of transcription, simultaneously with the hormone to 9-day old rats. On day 12 actinomycin D inhibited hydrocortisone-induced changes in the profile of enzyme activities along the villus-crypt axis and suppressed the appearance of asialylated forms of enzymes manifested precociously in the differentiating crypt cells under the effect of the hormone. These findings were correlative with sialyltransferase activity along the villus-crypt axis. PMID- 2222501 TI - Dopaminergic mechanisms in the locomotor stimulant effects of nicotine. PMID- 2222502 TI - Inhibition of mitochondrial carnitine palmitoyltransferases by adriamycin and adriamycin analogues. AB - Adriamycin (ADR; doxorubicin) and its highly lipophilic, less toxic analogue N benzyl-adriamycin-14-valerate (AD 198) were found to inhibit rat heart and liver carnitine palmitoyltransferases of both mitochondrial outer and inner membranes. The outer membrane enzyme was more sensitive to inhibition by these drugs than the inner membrane enzyme, and AD 198 was a more potent inhibitor of these enzymes than ADR. Other analogues of ADR, N-trifluoroacetyladriamycin-14-valerate (AD 32) and N-trifluoroacetyladriamycin-14-O-hemiadipate (AD 143), which are documented as being noncardiotoxic, were also more potent inhibitors of the mitochondrial carnitine palmitoyltransferases than ADR. Overall, the cardiac mitochondrial carnitine palmitoyltransferases seemed to be slightly more sensitive to the inhibitory effects of ADR and its analogues than the liver enzyme. ADR was an uncompetitive inhibitor with respect to palmitoyl-CoA and a noncompetitive inhibitor with respect to carnitine for both mitochondrial outer and inner membrane enzymes. Our data suggest that mitochondria can take up ADR and concentrate it within the matrix, as is known to happen with other positively charged compounds. More ADR was found associated with the mitochondrial inner membrane than with the outer membrane; this could be due to the greater protein content of the inner membrane rather than drug binding to cardiolipin. Although inhibition of cardiac inner membrane carnitine palmitoyltransferase has been implicated previously as part of the cardiotoxicity mechanism of ADR, the present findings with ADR and its noncardiotoxic analogues do not support this view. PMID- 2222503 TI - Depressive effects of lipid peroxides mediated via a purine receptor. Effect of lipid peroxide on the cortical synaptosomal GTPase activity. AB - A circadian rhythm of lipid peroxides (LPO) in mouse whole brain was observed with a negative correlation between LPO levels in cerebral cortex and the locomotor activity of mice. Intraperitoneal administration of t-butyl hydroperoxide (BPO) to mice decreased spontaneous locomotor activity in a dose dependent manner, and the effect was competitively antagonized by caffeine, suggesting a similar receptor. Cumene peroxide (CPO), BPO and known depressants such as phenobarbital and NaBr all stimulated GTPase activity in rat cerebral cortex synaptosomes. In contrast, stimulants, such as caffeine and amphetamine, inhibited GTPase activity. Using fresh and aged synaptosomes which differed markedly in endogenous LPO levels, it appeared as if the LPO competitively inhibited inosine-induced GTPase activity, suggesting that the receptor of LPO is the same as that of inosine. From these results, it is concluded that LPO in brain act as depressants whose activity can be competitively antagonized by caffeine, and that the effects of LPO are mediated through a purine receptor. PMID- 2222504 TI - Iron release and erythrocyte damage in allyl alcohol intoxication in mice. AB - Allyl alcohol administration in a toxic dose (1.5 mmol/kg) to starved mice causes the development of hemolysis in nearly 50% of the animals. Malonic dialdehyde (MDA) appears in plasma of the animals showing hemolysis. The treatment of mice with desferrioxamine after allyl alcohol intoxication completely prevents lipid peroxidation and hemolysis, suggesting the involvement of iron in the allyl alcohol-induced erythrocyte damage. Erythrocytes obtained from intoxicated mice before the development of hemolysis show, upon incubation, release of iron, lipid peroxidation and lysis. Studies carried out with reconstituted systems of erythrocyte lysates, containing ghosts and different fractions of erythrocyte cytosol and incubated in the presence of acrolein (the major metabolite of allyl alcohol), strongly suggest that iron is released from hemoglobin. This iron appears to promote lipid peroxidation which is accompanied by erythrocyte lysis. Thus, the allyl alcohol-induced hemolysis appears to be a model for iron delocalization from iron stores. PMID- 2222505 TI - Early mitochondrial disfunction in bromobenzene treated mice: a possible factor of liver injury. AB - The membrane potential of liver mitochondria isolated from bromobenzene treated mice was studied. Specifically, the efficiency of the energy-transducing mitochondrial membrane was measured during the phase between the occurrence of a massive loss of hepatic GSH, after 2-3 hr of bromobenzene intoxication, and the appearance of lipid peroxidation and cell death (12-15 hr after treatment). Partial uncoupling of oxidative phosphorylation was observed in mitochondria during the early period of intoxication (3-9 hr). These anomalies in oxidative metabolism did not result in irreversible damage to the mitochondrial inner membrane. The possibility that phenolic metabolites of bromobenzene are responsible for the uncoupling effects was examined. Orto- and especially para bromphenol reproduced the alterations of mitochondrial function when added to normal mitochondria at concentrations comparable to those found in the livers of the intoxicated animals. Since the concentration of the bromophenols (especially p-bromophenol) largely increases after the intoxication times as tested here, mitochondrial uncoupling may represent a mechanism of liver damage acting synergistically with or even independently of other factors such as oxidative stress and lipid peroxidation. PMID- 2222506 TI - Irreversible inhibition of rat S-adenosylmethionine decarboxylase by 5'-([(Z)-4 amino-2-butenyl]methylamino)-5'-deoxyadenosine. AB - 5'-([(Z)-4-Amino-2-butenyl]methylamino)-5'-deoxyadenosine [Z)-AbeAdo) was tested in vitro and in vivo as a potential inhibitor of S-adenosyl-L-methionine decarboxylase (AdoMetDC), a pyruvoyl-containing enzyme, purified from rat liver. In vitro (Z)-AbeAdo produces a time- and dose-dependent irreversible inhibition of the enzyme. Saturation kinetics are observed when the enzyme is preincubated with (Z)-AbeAdo in the presence of 50 microM putrescine, a known activator of AdoMetDC. Under these conditions kinetic constants were measured (Ki = 0.56 +/- 0.04 microM; tau 1/2 = 0.51 +/- 0.03 min). The inhibition is not relieved by prolonged dialysis of the inactivated enzyme. The turnover number for (Z)-AbeAdo, i.e. the number of inactivator molecules required to inactivate one enzyme molecule, is approximately 1.5. The selectivity of (Z)-AbeAdo was explored: the compound is not a substrate of adenosine deaminase, mitochondrial monoamine oxidase and diamine oxidase, but is slowly oxidized by benzylamine oxidase from rat aorta. The (E)-isomer of AbeAdo, is at least 100-fold less active than (Z) AbeAdo as a time-dependent inhibitor of rat liver AdoMetDC. In rats, intraperitoneal administration of (Z)-AbeAdo produces a rapid, long-lasting and dose-dependent decrease of AdoMetDC activity in ventral prostate, testis and brain. PMID- 2222507 TI - Failure of gentamicin to elevate cellular malondialdehyde content or increase generation of intracellular reactive oxygen species in primary cultures of renal cortical epithelial cells. AB - The role of lipid peroxidation in gentamicin cytotoxicity was assessed in primary cultures of renal cortical epithelial cells. The cellular content of malondialdehyde (MDA), one of the end products of lipid peroxidation, was determined, and the intracellular generation of reactive oxygen species, one of the events commonly occurring at the beginning of the process of lipid peroxidation, was estimated. Exposures to gentamicin were chosen that preceded or accompanied overt toxicity. MDA was determined by the thiobarbituric acid reactive substances assay. Intracellular generation of reactive oxygen species was estimated by quantitating the fluorescence of 2',7'-dichlorofluorescein (DCF'), a fluorophore formed by the reaction of the deacetylation product (2',7' dichlorofluorescein, DCF) of the fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFDA) with reactive oxygen species. Neither elevated MDA content nor intracellular generation of reactive oxygen species was observed in primary cultures of renal cortical epithelial cells treated with gentamicin, using exposures which preceded or accompanied overt toxicity. We conclude that lipid peroxidation does not play a role in gentamicin cytotoxicity. PMID- 2222508 TI - An evaluation of the redox cycling potencies of paraquat and nitrofurantoin in microsomal and lung slice systems. AB - The redox cycling abilities of the pulmonary toxins paraquat and nitrofurantoin have been compared with those of the potent redox cyclers, diquat and menadione in lung and liver microsomes by using the oxidation of NADPH and consumption of oxygen. The relative potencies of these compounds to undergo redox cycling were in the order: diquat approximately menadione much greater than paraquat congruent to nitrofurantoin. This was partly attributed to the much lower affinity (Km) of lung and liver microsomes for paraquat and nitrofurantoin than for diquat and menadione. The potential to redox cycle was assessed in an intact cellular system by determining the oxygen consumption of rat lung slices in the presence (10(-6), 10(-5) and 10(-4) M) or absence of each of the four substrates. At concentrations of paraquat (10(-5) M) known to be accumulated by lung slices, a small but significant stimulation of lung slice oxygen uptake was observed. Nitrofurantoin (10(-4)-10(-6) M) did not affect lung slice oxygen uptake in lung slices, an observation consistent with its being a poor redox cycling compound, which is not actively accumulated into lung cells. This data has important implications in assessing the risk of exposure to paraquat. Low levels of paraquat would not be expected to cause lung damage because insufficient compound is present in the lung to exert its toxicity by redox cycling (due to the high Km observed). PMID- 2222509 TI - Common pharmacological and physico-chemical properties of 5-HT3 binding sites in the rat cerebral cortex and NG 108-15 clonal cells. AB - On account of the postulated existence of 5-HT3 receptor subtypes, the respective physico-chemical and pharmacological properties of specific binding sites for the potent 5-HT3 antagonist [3H]zacopride were compared using membranes from the rat posterior cortex or neuroblastoma-glioma NG 108-15 clonal cells. In both membrane preparations, [3H]zacopride bound to a single class of specific sites with a Kd close to 0.5 nM. However, the Bmax value in NG 108-15 cell membranes (970 +/- 194 fmol/mg protein) was approximately 50 times larger than that in cortical membranes (19 +/- 2 fmol/mg protein). The specific binding of [3H]zacopride was equally affected by temperature, pH and molarity of the assay medium, and equally insensitive to thiol- and disulfide-reagents (N-ethylmaleimide, p chloromercuribenzene sulfonic acid, dithiothreitol) and GTP in cortical as well as NG 108-15 cell membranes. Determination of the molecular size of [3H]zacopride specific binding sites by radiation inactivation yielded values close to 35 kDa for both membrane preparations. Finally, a highly significant positive correlation (r = 0.979) was found between the respective pKi values of 34 different drugs for their inhibition of [3H]zacopride specific binding to cortical or NG 108-15 cell membranes. Among them, the most potent was S( )zacopride (pKi = 9.55), followed by BRL 43964, ICS 205-930, quipazine, R(+)zacopride, GR 38032F and MDL 72222. Atypical antidepressants (mianserin, amoxapine) and neuroleptics (clotiapine, loxapine and clozapine) were active in rather low concentrations (pKi less than 6.5), suggesting that recognition of 5 HT3 sites might be relevant to part of the in vivo effects of these drugs. Such identical physico-chemical and pharmacological properties of [3H]zacopride specific binding in cortical and NG 108-15 cell membranes strongly suggest that the same 5-HT3 receptor (subtype?) exists in these two preparations. PMID- 2222510 TI - Stimulation and inhibition of adenylyl cyclase by distinct 5-hydroxytryptamine receptors. AB - 5-Hydroxytryptamine (serotonin, 5-HT) stimulates basal adenylyl cyclase activity in membranes from guinea pig or rat hippocampi, but 5-HT inhibits forskolin stimulated adenylyl cyclase activity in these same membranes. The opposing effects of 5-HT on adenylyl cyclase activity indicate that distinct 5-HT receptors, positively and negatively coupled to adenylyl cyclase, are present in these membranes. Stimulation of adenylyl cyclase activity is mediated by two distinct 5-HT receptors. The receptor with lower affinity for 5-HT, designated as RL, is apparently homologous with a 5-HT receptor present in rat collicular membranes, but it is not homologous with the stimulatory receptor characterized in neuroblastoma hybrid cell (NCB-20) membranes. The receptor with higher affinity for 5-HT is homologous with the 5-HT1A binding site. The magnitude of stimulation by 5-HT1A receptors is variable with respect to stimulation by RL and is sometimes completely absent. Inhibition of forskolin-stimulated adenylyl cyclase activity, in membranes from either rat or guinea pig hippocampus or rat cortex, is a functional correlate of the 5-HT1A binding site. This inhibitory response was used to determine the pharmacological characteristics of drugs that reportedly have high affinity for 5-HT1A binding sites, such as 1-[2-(4 aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (PAPP) and (-)pindolol. PAPP inhibited adenylyl cyclase activity in guinea pig hippocampal membranes with an EC50 value of 27 +/- 3 nM. (-)Pindolol was a partial agonist in inhibiting adenylyl cyclase activity in guinea pig and rat hippocampal membranes. Because of the low intrinsic activity of (-)pindolol, it was tested as an antagonist of the inhibition produced by 5-HT1A receptor agonists in rat hippocampal membranes. The Kb of (-)pindolol was 40 nM as measured by a Schild plot. (-)Propranolol was a simple competitive antagonist at the rat hippocampal receptor with a Kb value of 550 nM. In summary, guinea pig and rat hippocampal membranes possess two distinct populations of 5-HT receptors, a 5-HT receptor that mediates inhibition of adenylyl cyclase activity and is pharmacologically homologous with the 5-HT1A binding site, and a stimulatory receptor that appears to be homologous with the 5 HT receptor first characterized in infant rat collicular membranes. PMID- 2222511 TI - Reversible inhibition of rat hepatic glutathione S-transferase 1-2 by bilirubin. AB - The inhibition of rat hepatic glutathione (GSH) S-transferase 1-2 by bilirubin exhibited pseudo first-order kinetics with k(obs) values of 0.0214 +/- 0.0005 and 0.040 +/- 0.008 sec-1 at 4 and 8 microM bilirubin, when followed to 72 and 84% completion respectively. These correspond to calculated second-order rate constants of 5.3 +/- 0.1 x 10(3) and 5.0 +/- 1.0 x 10(3)/M.sec. The extent of inhibition of the transferase increased with bilirubin concentration, with half maximal inhibition at 4 microM bilirubin. Inhibition was reversed by 10-fold dilution of bilirubin or by increasing the pH from 6.0 to 7.4. Premixing 0.2 to 0.5 microM albumin, hemoglobin or aldolase with bilirubin prevented inhibition of GSH S-transferase 1-2. Protection by these proteins occurred at a selected high concentration (0.2 to 0.4 microM) at which they reduced free bilirubin to concentrations (less than 0.5 microM) that did not inhibit isoenzyme 1-2 significantly. No protection was afforded by a selected low protein concentration (0.001 to 0.01 microM) which did not strikingly reduce bilirubin levels in solution. We conclude that bilirubin inhibition of GSH S-transferase 1-2 appears to be a second-order process; the reaction is clearly first-order with respect to GSH S-transferase and appears also to be first-order with respect to bilirubin. It is proposed that (a) inhibition of GSH S-transferase 1-2 results from slow, reversible bilirubin binding, and (b) added proteins appear to prevent GSH S transferase inhibition by binding high molar ratios of bilirubin. PMID- 2222512 TI - The inhibition of human prostatic aromatase activity by imidazole drugs including ketoconazole and 4-hydroxyandrostenedione. AB - Ketoconazole, an orally active imidazole drug and bifonazole, clotrimazole, econazole, isoconazole, miconazole and tioconazole are known as inhibitors of cytochrome P450 dependent steroidogenic enzymes including human placental aromatase. The aim of the present study was to investigate the effectiveness of these imidazole drugs to inhibit human prostatic aromatase activity compared with the known inhibitor of aromatase 4-hydroxyandrostenedione (4-OHA). The imidazole drugs and 4-OHA inhibited prostatic aromatase activity in a dose-dependent manner. The order of decreasing inhibitory potency determined from IC50 values (mumol/L) was: 4-OHA (1.57) greater than bifonazole (1.6) greater than tioconazole (1.69) greater than clotrimazole (1.73) greater than econazole (1.87) greater than miconazole (2.0) greater than isoconazole (2.2) greater than ketoconazole (4.7). The IC50 values for the inhibition of prostatic homogenate aromatase activity are 3-9-fold higher than that for the inhibition of human placental aromatase activity, previously reported, except that of ketoconazole which was 1.5-fold lower than that for the inhibition of placental microsomal aromatase. PMID- 2222514 TI - Location and characterization of the suramin binding sites of human serum albumin. AB - The objective of the present study was to investigate the location of the high affinity suramin binding sites on the human serum albumin molecule. For this purpose, circular dichroism and equilibrium dialysis experiments were performed on the interaction between suramin and a large peptic and a large tryptic fragment of albumin, the former comprising domains one and two of the albumin structure and the latter domains two and three. The equilibrium dialysis experiments revealed that albumin and the fragments have a comparable total affinity for suramin. Furthermore, all three proteins display a similar pH dependence of the unbound fraction of suramin. The circular dichroism experiments revealed that only the suramin-albumin and the suramin-peptic fragment complexes can undergo the pH dependent neutral-to-base or N-B conformational change, whereas the suramin-tryptic fragment complex lacks this ability. It is likely that the main parts of the high-affinity binding sites for suramin are located in domain two of the albumin molecule. The nature of these binding sites is discussed. The deprotonation of histidine and other positively charged residues taking part in salt bridges between suramin and albumin is, in all probability, the main cause of the decrease in affinity of suramin for albumin as the pH is raised from 6 to 9. PMID- 2222513 TI - The effect of adriamycin on glycerolphosphate acyltransferase and lipid metabolism in rat hepatocytes in monolayer culture. AB - Total and mitochondrial glycerolphosphate acyltransferase activities were measured after 24 hr exposure of rat hepatocytes to Adriamycin. Both activities decreased with increasing concentrations of Adriamycin. The activity of the microsomal glycerolphosphate acyltransferase, which was determined from the difference between the total and mitochondrial enzyme activity, also decreased with increasing drug concentration. The effect on glycerolphosphate acyltransferase was specific as there was no change in lactate dehydrogenase or cytochrome oxidase activity in this time period. Adriamycin did not inhibit mitochondrial glycerolphosphate acyltransferase activity in vitro. After 24 hr exposure of hepatocytes to Adriamycin no change was observed in the biosynthesis of phosphatidylcholine or triacylglycerol. Secretion of lipid into the medium was measured over the subsequent 24 hr. There was a significant reduction in very low density lipoprotein secretion as measured by triacylglycerol secretion from cells incubated with 5 microM Adriamycin. Cells were damaged by the 48 hr exposure to 1 microM and higher concentrations of Adriamycin as evidenced by a fall in lactate dehydrogenase activity in these cells. The secretion of lysophosphatidylcholine, as measured by the incorporation of [3H]glycerol into medium lysophosphatidylcholine, was significantly increased when cells were incubated with 5 microM Adriamycin. The results are discussed in relation to the effect of Adriamycin on hepatic lipid metabolism and the cardiotoxicity of the drug. PMID- 2222515 TI - In vivo evidence for protease-catalysed mechanism providing bioactive tumor necrosis factor alpha. AB - Mice pretreated by intravenous injection of 42 mg/kg of the serine protease inhibitor alpha 1-antitrypsin prior to a hepatotoxic dose of D galactosamine/lipopolysaccharide (GalN/LPS) were fully protected against hepatitis. Pretreatment with alpha 1-antitrypsin with doses up to 300 mg/kg at different times failed to protect galactosamine sensitized animals against tumor necrosis factor alpha (TNF alpha)-induced hepatitis. No bioactive TNF alpha was detectable in serum of mice protected against GalN/LPS-induced hepatitis by pretreatment with alpha 1-antitrypsin. In contrast, abundant amounts of TNF were found in sera of GalN/LPS-treated control animals. It is concluded that a serine protease sensitive to alpha 1-antitrypsin provides bioactive TNF alpha by proteolytic cleavage of a TNF alpha precursor. PMID- 2222516 TI - Inhibition of rat and human glutathione S-transferase isoenzymes by ethacrynic acid and its glutathione conjugate. AB - Ethacrynic acid, a potent inhibitor of glutathione S-transferases (GST), has been shown to enhance the cytotoxicity of chlorambucil in drug resistant cell lines, but a definite mechanism has not been established. Both covalent binding to GST and reversible inhibition of GST have been reported. In the present study no irreversible inhibition was observed: for all rat GST tested, inactivation was complete within 15 sec at 0 degree, and dialysis of GST after incubation with ethacrynic acid gave complete recovery of enzyme activity for all isoenzymes tested. Moreover, the inhibition was competitive towards 1-chloro-2,4 dinitrobenzene and non-competitive towards glutathione for rat isoenzyme 1-1. Strong inhibition of both human and rat GST of the alpha-, mu- and pi-classes was obtained with ethacrynic acid, while conjugation of ethacrynic acid with glutathione did not abolish its inhibiting properties. For the alpha-, mu- and pi class I50 values (microM) were 4.6-6.0, 0.3-1.9 and 3.3-4.8, respectively for ethacrynic acid, and 0.8-2.8, less than 0.1-1.2 and 11.0, respectively for its glutathione conjugate. Of all isoenzymes tested the human isoenzyme mu is most sensitive to the action of both ethacrynic acid and its glutathione conjugate. PMID- 2222517 TI - Enantioselective and diastereoselective aspects of the oxidative metabolism of metoprolol. AB - Enantio- and diastereoselective aspects of oxidative metabolism of metoprolol (1) were examined in the presence of rat liver and human liver microsomes using a pseudoracemate of 1, made up of equal molar (2R)-1-d0 and (2S)-1-d2, as substrate. Both O-demethylation and alpha-hydroxylation showed only slight enantioselectivity, 2R/2S ratios being 1.18 and 0.93 for these pathways in rat liver microsomes and 1.09 and 0.92 in human liver microsomes. In the presence of the rat liver microsomal fraction, alpha-hydroxylation yielded predominantly the 1'R-hydroxy product, 1'R/1'S ratio greater than 12, regardless of the stereochemistry of the side chain. In humans (extensive metabolizers) administered a single 50 mg oral dose of pseudoracemic metoprolol tartrate, urinary alpha-hydroxymetoprolol (2) accounted for 9.3 +/- 2.4% of the dose, 2R/2S ratio 0.85 +/- 0.14, and the carboxylic acid metabolite 4, accounted for 52.7 +/- 6.8% of the dose, 2R/2S ratio 1.15 +/- 0.09. The data suggested that preferential O-demethylation of the (2R)-enantiomer of 1 could contribute to the 2S greater than 2R plasma ratio of metoprolol enantiomers observed in this population. PMID- 2222518 TI - 7-Alkoxyquinolines: new fluorescent substrates for cytochrome P450 monooxygenases. AB - A series of 7-alkoxyquinolines was synthesized and tested as substrates with hepatic microsomes prepared from male Wistar rats. Microsomal O-dealkylation rates and kinetic constants were determined for the 7-alkoxyquinolines with microsomes from control, 3-methylcholanthrene (MC)-pretreated, and phenobarbitone (PB)-pretreated rats. Structure-activity relationship studies indicated that the 7-benzyloxyquinoline was the most rapidly metabolized substrate for control microsomes and those from PB-pretreated rats, whereas the 7-ethoxy- and 7 propoxyquinolines were O-dealkylated more rapidly by microsomes of MC-pretreated animals. Differences in activities occurred in Vmax and apparent Km values; however, there does not appear to be a correlation between these two values for the different quinoline substrates. Apparent Km and Vmax values for the 7 alkoxyquinolines were: control microsomes, Km = 71-773 microM, Vmax = 0.37-8.4 nmol 7-quinolinol/min/mg protein; MC microsomes, Km = 0.5-14 microM, Vmax = 0.29 2.7 nmol 7-quinolinol/min/mg protein; PB microsomes, Km = 2.8-46 microM, Vmax = 0.9-12 nmol 7-quinolinol/min/mg protein. All of the quinoline substrates gave Type I binding spectra with control and MC microsomes. With PB microsomes, Type I. Reverse Type I, and a mixture of the two types of binding spectra were observed. Comparisons of the structure-activity relationships, levels of induction, and kinetic constants were made with 7-alkoxycoumarin and 7 alkoxyphenoxazone analogs. In addition, three new coumarin substrates (7-pentoxy , 7-hexoxy-, and 7-benzyloxycoumarin) are described. PMID- 2222519 TI - Modulation of doxorubicin-induced chromosomal damage by calmodulin inhibitors and its relationship to cytotoxicity in progressively doxorubicin-resistant tumor cells. AB - Modulation of doxorubicin (DOX) cytotoxicity by the calmodulin inhibitor trifluoperazine (TFP) in progressively doxorubicin-resistant L1210 mouse leukemia cells is unrelated to effects on drug accumulation. Based on the clastogenic activity of DOX, the effects of TFP and the selective calmodulin inhibitor 1,3 dihydro-1-[1-[4-methyl-4H,6H-pyrrolo[1,2-a][4,1]- benzoxazepin-4-yl-methyl]-4 piperidinyl]-2H-benzimidazol-2-o ne(1:1) maleate (CGS9343B) on DOX-induced chromosomal damage and its relationship to cytotoxicity were evaluated in sensitive and progressively DOX-resistant L1210 cells. Potentiation of DOX cytotoxicity by CGS9343B (a potent inhibitor of calmodulin which does not inhibit protein kinase C) was related to the level of resistance. Further, for equivalent cytotoxicity, cellular DOX levels in the absence versus the presence of TFP or CGS9343B were markedly higher. Exposure to calmodulin inhibitors following DOX treatment enhanced chromosomal aberrations and cytotoxicity. Maximal effects of calmodulin inhibitors were apparent when used during and after DOX treatment, and potentiation of cytotoxicity was related to modulation of DOX-induced chromosomal aberrations. Results suggest that inhibition of calmodulin-regulated processes is a potential target in the modulation of DNA damage/repair, and could play a pivotal role in the expression of "acquired resistance" to DOX. PMID- 2222520 TI - Effect of normal aging on the activity of human hepatic cytochrome P450IIE1. PMID- 2222522 TI - Interaction of cimetidine with human serum albumin. AB - Ultrafiltration studies have detected the existence of a weak interaction between cimetidine and human serum albumin, a finding supported by corresponding studies with this xenobiotic and bovine serum albumin. Furthermore, the binding characteristics of the interaction with human serum albumin (4 sites, K = 630 M 1) more than suffice to account for the proportion of protein-bound drug in the serum of patients subjected to cimetidine therapy. Thus, although alpha 1-acid glycoprotein is usually regarded as the specific transporter of basic drugs, the present evidence implicates albumin as the likely binding protein for cimetidine in serum. PMID- 2222523 TI - Labeling of rat heart muscarinic receptors using the new M2 selective antagonist [3H]AF-DX 384. PMID- 2222524 TI - [Ligand-exchange chromatography of proteins and enzymes]. AB - Current state of the ligand-exchange chromatography (metal chelate affinity chromatography) of proteins and enzymes is reviewed. This technique is based on the ability of proteins to bind metal ions immobilized on chelate gels. The influence of pH, composition of buffer, type of stationary ligand and nature of metal ions on the chromatographic behaviour of proteins is discussed. PMID- 2222521 TI - Metabolism of ethyl 2-carbamoyloxybenzoate (4003/2), a prodrug of salicylic acid, carsalam and salicylamide. AB - The metabolites of 4003/2 observed in vivo have been produced by incubation in vitro of 4003/2 with liver post-mitochondrial supernatants from rat, rabbit and dog. The metabolites were characterized by UV, i.r., NMR, MS and HPLC. All the metabolites detected have been or are in use as drugs for the relief of pain and inflammation. Hence, the new drug 4003/2 is a pro-drug of salicylic acid, carsalam and salicylamide. PMID- 2222526 TI - [Highly selective labeling of the E. coli RNA-polymerase promoter complex with reactive derivatives of oligonucleotide primers of various specificity]. AB - A technique of highly selective affinity labelling, which includes covalent modification of the enzyme-T7A2 promoter complex with reactive oligonucleotide derivatives and subsequent elongation of the attached oligonucleotide residue with a radioactive substrate was used to study the product-binding site of E. coli RNA polymerase. Different oligonucleotides complementary to the T7A2 promoter (with lengths ranging from 2 to 8 residues) containing 5'-terminal phosphorylating, alkylating or aldehyde groups were used for the labelling. The procedure resulted in labelling DNA and beta-, beta'- or sigma-subunits of the enzyme, which are therefore believed to contact with growing RNA in the course of initiation. Consideration of the labelling patterns as a functions of the oligonucleotide's length as well as of the structure and chemical specificity of the reactive groups led to a tentative topographic scheme of the RNA polymerase product-binding region. PMID- 2222525 TI - [Reconstruction of the synthetic gene for human interleukin-2]. AB - Chemical-enzymatic synthesis and cloning of the DNA fragment coding for the human interleukin-2 signal sequence was accomplished. A hybrid plasmid pSIL-2 containing the gene of the human interleukin-2 with this signal sequence was constructed for effective expression of the gene in eukaryotic systems. A variant permitting the removal of the interleukin-2 stop-codons was obtained, which is suitable for the construction of chimeric genes containing the interleukin-2 gene sequence at the 5'-end. PMID- 2222527 TI - [Complementary addressed alkylation of Escherichia coli 16S rRNA with 2',3'-O-[4 N-methyl-N-(2-chloroethyl)aminobenzylidene]m derivatives of oligodeoxyribonucleotides. IV. Determination of binding sites of 16S rRNA with benzylidene derivatives of d(pACCTTGTT)rA, d(pTTACGACT)rU, d(TTTGCTCCCC)rA]. AB - By site-directed alkylation of 16S rRNA with benzylidene derivatives of d(pACCTTGTT)rA (II), d(pTTACGACT)rU (III), d(pTTTGCTCCCC)rA (IV) (reagents (II)- (IV] followed by the RNase H treatment a number of 16S rRNA fragments have been obtained. Hybridisation of these fragments with restriction fragments of plasmid pKK 3535, containing operon rrnB of E. coli rRNAs, led to the identification of all reagents' binding sites in 16S rRNA. Good correlation is found between estimated stability of non-perfect 16S rRNA.oligodeoxyribonucleotide duplexes and the level of modification of this site with alkylating derivative of the same oligodeoxyribonucleotide. With high concentration of the reagents (II)--(IV) ((2 5) x 10(-5) M) the site-directed alkylation proceeds not only at the desired site but also at other sites corresponding to non-perfect duplexes between 16S rRNA and the reagents. It should be noted that the modification mainly occurs in the non-perfect duplexes, carrying mismatched bases at the termini. Influence of the secondary structure of 16S rRNA on the site-directed modification is discussed. PMID- 2222528 TI - [The structure of carbohydrate chains of hemagglutinin and neuraminidase of influenza virus B/Leningrad/179/86]. AB - The main surface glycoprotein, hemagglutinin (HA), was obtained by treatment of influenza virus B/Leningrad/179/86 with bromelain. Amino acid and monosaccharide compositions of HA and neuraminidase (NA, earlier isolated from the same virus) were determined, thus showing HA and NA to contain 8-10 and 2 carbohydrate chains, respectively. The carbohydrate fragments were cleaved off by the alkaline LiBH4 treatment, the oligosaccharides released were reduced with NaB3H4 and fractionated by two-step HPLC on Ultrasphere-C18 and Zorbax-NH2 columns. Some higher mannose and complex oligosaccharides were identified in both cases by comparison with nonlabelled oligosaccharides of the known structure. The data obtained show that surface glycoproteins of influenza virus A and B are rather similar with regard to structure and heterogeneity of their carbohydrate chains. PMID- 2222529 TI - [Synthesis and mass-spectrometric analysis of N-cycloalkyl derivatives of carminomycin, daunorubicin and their analogs]. AB - Condensation of carminomycin or daunorubicin with glutaric dialdehyde in the presence of NaBH3CN yielded 3'-deamino-3'-piperidinocarminomycin or 3'-deamino-3' piperidinodaunorubicin and corresponding (13-R, S)-dihydroderivatives. To prepare similar derivatives of 14-hydroxycarminomycin or doxorubicin, 13-dimethylketals of 14-bromocarminomycin or 13-bromodaunorubicin were used in the reaction of reductive alkylation with glutaric or glycolic dialdehyde to give 3'-deamino-3' piperidino- or 3'-deamino-3'-morpholino derivatives of 13-dimethylketals of 14 bromocarminomycin or daunorubicin, respectively. After deblocking and subsequent hydrolysis of these compounds 3'-deamino-3'-piperidino- and 3'-deamino-3' morpholino derivatives of 13-hydroxycarminomycin or doxorubicin were prepared. Reduction of the antibiotic derivatives under mass spectrometry conditions was demonstrated. PMID- 2222530 TI - [Analysis of highly tritium-labeled alanine using 3H- and 1H-NMR]. AB - A method has been developed for the analysis of deuterium oxide solutions of tritiated alanine eight-component isotopic mixtures by using high resolution 3H and 1H NMR spectra at frequencies 266.8 and 500.13 MHc, respectively. Approaches have been worked out for the determination of qualitative composition of the mixtures and spectral parameters. PMID- 2222531 TI - Diminished incidence of severe rheumatoid arthritis associated with oral contraceptive use. AB - It has been suggested that the negative association between rheumatoid arthritis (RA) and oral contraceptive (OC) use might be limited to the more severe forms of RA. To investigate this further, we studied 121 consecutive female patients with definite RA, 52 female patients with probable RA, and 378 female controls. All patients had RA symptoms of recent onset. After a mean followup period of 6 years, patients with definite RA were classified as having either a severe disease course (n = 76) or a mild disease course (n = 45). The negative association between OC use prior to the onset of RA symptoms and the development of RA was limited to those patients with definite RA who had a severe disease course. We therefore conclude that OC use prior to the onset of RA symptoms is only associated with a reduction in the incidence of severe RA. This may explain the divergent results of previous studies. PMID- 2222532 TI - Cellular immune response toward human articular chondrocytes. T cell reactivities against chondrocyte and fibroblast membranes in destructive joint diseases. AB - Articular cartilage is one of the major targets in destructive joint diseases in humans. We studied cellular immune reactions against cartilage cell-surface membranes, because it has recently been suggested that these represent possible antigenic structures, based upon the observation of autoantibodies with this specificity in certain joint diseases. A striking T cell reactivity toward chondrocyte membranes was found both in blood and synovial tissue from patients with rheumatoid arthritis. This reactivity was strongly dependent on the presence of monocytes and had all the characteristics of an antigen-driven process. Clonal analysis demonstrated high precursor frequencies in peripheral blood T cells that were reactive against chondrocyte membranes. This response to chondrocyte membranes greatly exceeded the T cell stimulation induced by membranes from other sources such as fibroblasts or epithelial cells. In contrast to patients with rheumatoid arthritis, individuals with osteoarthritis showed a strong peripheral blood and synovial fluid T cell response not only to chondrocyte membranes, but also to fibroblast membrane material. However, there was no reactivity to epithelial cell membranes. Normal donors generally did not show significant responses to any membrane preparation. These data indicate that there is a strong T cell reactivity toward chondrocyte membranes in destructive joint disorders, and this may significantly contribute to the pathogenetic processes that occur in these diseases. PMID- 2222533 TI - Relationship of glucocorticoid dosage to serum bone Gla-protein concentration in patients with rheumatologic disorders. AB - Serum bone Gla-protein (BGP) measurements in 50 rheumatic disease patients receiving long-term prednisone therapy revealed an inverse relationship (r = 0.71, P less than 0.001) between serum BGP levels and prednisone dosage. Multiple regression analysis demonstrated significant relationships (R2 = 0.72, P less than 0.001) between serum BGP1/2 and prednisone dosage, dosage2, serum creatinine, age, and an age-creatinine interaction. This model predicts the suppression of serum BGP with low dosages of steroids and 50% suppression with dosages of 20-25 mg/day. PMID- 2222534 TI - Collagen-collagen versus collagen-proteoglycan interactions in the determination of cartilage strength. AB - For articular cartilage to function as a stress-reducing layer in the joint, it must both deform to an appropriate level to achieve load-spreading as well as remain structurally coherent. Combined micromechanical and enzymatic studies of cartilage have demonstrated that the bulk of the extractable proteoglycans, while essential to the maintenance of compressive stiffness, contribute little to its cohesive strength. The study reported here clarifies fundamental aspects of the relationship between matrix components and the biomechanical function of cartilage. PMID- 2222535 TI - Binding of anti-DNA antibodies and inhibition of glomerulonephritis in MRL lpr/lpr mice by heparin. AB - Heparin was found to inhibit the DNA binding of antibodies eluted from kidneys of both humans and MRL-lpr/lpr mice with systemic lupus erythematosus. Treatment of MRL-lpr/lpr mice with low doses of heparin significantly inhibited renal damage. These results suggest that low-dose heparin might be useful in preventing renal damage in patients with lupus nephritis. PMID- 2222536 TI - Renal disease in chronic arthritis of childhood. A study of urinary N-acetyl-beta glucosaminidase and beta 2-microglobulin excretion. AB - Urinalyses of randomly obtained samples from children with various types of chronic arthritis revealed proteinuria in 2.3% of patients, hemoglobinuria in 3.5%, erythrocyturia in 4.1%, and leukocyturia in 5.3%; these frequencies are within the range found by screening school children. However, raised urinary levels of N-acetyl-beta-glucosaminidase and/or beta 2-microglobulin (both sensitive measures of renal tubular damage) were found more frequently in children with chronic arthritis than in controls (P less than 0.0001). Abnormalities of either N-acetyl-beta-glucosaminidase or beta 2-microglobulin excretion were associated with active arthritis as measured by physician global estimate of disease activity, with a polyarticular onset of juvenile rheumatoid arthritis, and with the use of slow-acting antirheumatic drugs or the concurrent use of more than 1 nonsteroidal antiinflamtory drug. Abnormal renal tubular function appears to be common in chronic arthritis of childhood. The long-term consequences of this abnormality remain to be elucidated. PMID- 2222537 TI - Pseudotumor of the craniocervical junction during long-term hemodialysis. AB - A systematic study of the upper cervical spine was performed using magnetic resonance imaging in 25 patients (15 men and 10 women) who had been undergoing hemodialysis for more than 10 years. Seven pseudotumors of the periodontoid soft tissue were disclosed, which were similar to the pannus recently described in rheumatoid arthritis. Bone cystic radiolucencies were observed in association with these pseudotumors in 5 patients. The radiolucencies were located in the atlas (1 in the lateral mass and 1 in the anterior branch) and in the axis (3 in the odontoid process and 1 in the vertebral body). No horizontal or vertical atlantoaxial subluxation was demonstrated. These features were observed only in patients who had amyloid arthropathy. They could be a frequent, yet thus far little-recognized, feature of beta 2-microglobulin amyloidosis. PMID- 2222538 TI - Human immunodeficiency virus-associated psoriasis, psoriatic arthritis, and Reiter's syndrome: a disease continuum? AB - The presence of peripheral arthritis and HLA-A, B, C, DR, and DQ antigens was evaluated prospectively in 18 Caucasian men with human immunodeficiency virus associated psoriasis. An asymmetric polyarthritis occurred in 32% of the patients and correlated with the presence of HLA-B27. Extensive clinical overlap between psoriatic arthritis, psoriasis, and Reiter's syndrome was noted. No significant excess of the HLA antigens previously found to be associated with psoriasis was seen, which suggests that human immunodeficiency virus-associated psoriasis per se may instead constitute another form of spondylarthropathy that is more closely related to Reiter's syndrome. PMID- 2222539 TI - Intravenous pulse cyclophosphamide therapy in myositis and Sjogren's syndrome. AB - We describe a patient with primary Sjogren's syndrome who developed myositis. The results of muscle pathologic analysis before and after treatment with monthly pulses of cyclophosphamide (intravenously), are presented. PMID- 2222540 TI - D-penicillamine-induced lupus erythematosus. AB - We describe a patient who presented with polyarthritis, pleurisy, rash, and a positive antinuclear antibody result after 5 years of D-penicillamine therapy. D penicillamine-induced antinuclear antibodies were mainly high-titer IgG directed against the (H2A-H2B)-DNA complex. Weak IgM activity with H1 and H2B was also observed. Withdrawal of D-penicillamine therapy resulted in improvement in clinical symptoms and gradual resolution of serologic abnormalities. PMID- 2222541 TI - Amyloidosis in Behcet's syndrome. AB - We investigated the frequency of amyloidosis in 99 consecutive patients (65 men and 34 women) with Behcet's syndrome. Rectal biopsies performed on all patients showed no amyloidosis by polarizing microscopy. The results of urinalyses were normal in all patients. Among 1,130 patients registered in our Behcet's syndrome outpatient clinic, 5 were found to have systemic amyloidosis, all of the AA type. PMID- 2222542 TI - Sulfonamides as antiinflammatory agents in the treatment of Wegener's granulomatosis. PMID- 2222543 TI - Successful use of cyclosporine for the treatment of aggressive pulmonary fibrosis in a patient with rheumatoid arthritis. PMID- 2222544 TI - Comment on the article by Pope et al. PMID- 2222545 TI - Factor B activation in systemic lupus erythematosus. PMID- 2222546 TI - Comment on the article by Calin et al. PMID- 2222547 TI - [Biochemical aspects of the evaluation of fixed drug combinations]. AB - Various disciplines have to contribute to the general problem of the evaluation of fixed dose combination drugs, as for instance (clinical) pharmacology, biometry, scientific drug regulations and public health officials. The EC guideline 75/318/EWG and its eludications as well as the German "Arzneimittelprufrichtlinien" of Dec. 14, 1989 (as referred to in the "Arzneimittelgesetz" of 1986) required that such issues concerning fixed dosage combination drugs must be considered and taken into account. In this framework it is the responsibility of biometry to both to guarantee the use of a valid study design to assure interpretation of the results and to quantify the reliability of pharmacological and clinical considerations. The following paper is concerned with biometrical aspects of the combination drug problem. Basic considerations from a clinical or a pharmacological point of view with respect to the question of whether fixed combination drugs are reasonable or not are not discussed. To support the use of combinations of drugs, a central argument is the improvement of the benefit risk relation compared with that of an adequate monotherapy. Beyond this the fixed combination drugs require additional arguments regarding the enhencement of the safety or the simplicity of the therapy fixing the ratio. It follows that fixed combination drugs have to be supported twice, first with respect to the combination itself, and second with respect to the fixed mixing ratio of its components. The biometrical aspects of the assessment of the gains from (fixed) drug combinations are related to the kind of benefit/risk improvement that is expected. In the first section we discuss some possible types of benefit and risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222549 TI - Studies of antidote therapy for nisoldipine intoxication in experimental animals. AB - In anesthetized rats under artificial respiration, intravenous infusion of nisoldipine (0.1 mg/kg x min) caused significant decreases in blood pressure, heart rate, cardiac output and peripheral resistance. The animals died 54.7 +/- 11.1 min after initiation of the infusion. The electrocardiogram showed sinus bradycardia, increasing AV blockade and displacement of the pacemaker into the AV node or the bundle of His. Survival time under nisoldipine infusion increased more than two-fold with simultaneous infusion of calcium gluconate, isoprenaline (isoproterenol) or dopamine. Norepinephrine (noradrenaline) had no significant effect on survival time; the latter decreased to 19.4 +/- 1.6 min by plasma volume expansion with polygeline. All antidotes prolonging survival time also normalized the cardiac output diminished after nisoldipine. Electrocardiographic changes were antagonized only by isoprenaline. Suitable antidotes for intoxication or over-dosage of nisoldipine are calcium salts as well as beta sympathomimetic drugs; sheer volume substitution and peripheral vascular constriction should not be resorted to. PMID- 2222548 TI - Effects of the new centrally acting muscle relaxant 7-chloro-N,N,3 trimethylbenzo[b]furan-2-carboxamide on motor and central nervous systems in rats. AB - Effects of KW-6629 (7-chloro-N,N,3-trimethylbenzo[b]furan-2-carboxamide) were studied with special reference to the effect on motor and central nervous systems using rats. The drug effectively reduced the motor coordination (rotarod), the anemic decerebrate rigidity, the crossed extensor reflex, and the gamma-activity indirectly recorded from muscle afferent discharges without showing the direct inhibitory effect on muscle spindles. KW-6629 depressed the polysynaptic and dorsal root reflexes without showing marked effect on the monosynaptic reflex in intact spinal cord rats. KW-6629 produced high-amplitude slow wave in the cerebral cortex in electroencephalogram (EEG). KW-6629 did not reduce the EEG after-discharges and behavioral convulsion (amygdaloid kindling). KW-6629 had no effect on the neuromuscular junction. These results suggest that KW-6629 is a centrally acting muscle relaxant which has a site of action in supraspinal structures. PMID- 2222551 TI - In vitro studies on interactions of iron salts and complexes with food-stuffs and medicaments. AB - It has been shown in the present study that food components such as phytic acid, oxalic acid, tannin, sodium alginate, choline and choline salts, vitamins A, D3 and E, soy oil and soy flour, do not undergo any interactions with iron(III) hydroxide polymaltose complex (Ferrum Hausmann). Phytic acid, oxalic acid, tannin and sodium alginate, however, react with iron(II) or iron(III)-salts at pH values of 3.0, 5.5 and 8.0, giving rise to iron complexes. Trimethylamine-N-oxide, which is present in fish meal, reacts with iron(II)-sulphate to produce iron(III) reaction products; it does not react with iron(III)-hydroxide polymaltose complex. Special soybean flours show no irreversible adsorption or precipitation with iron(III)-hydroxyide polymaltose complex over the pH range 3.0-8.0, in contrast to iron(II)-sulphate. Antacids containing aluminium hydroxide, talc, ion exchange resins or other unabsorbable, insoluble components absorb iron(III) hydroxide polymaltose complex in the pH range 3.0-8.0 in a reversible manner, while the strong adsorption or precipitation observed with iron(II)-sulphate at pH 8.0 is irreversible. No interaction was observed between the steroid hormones studied and iron(II)-sulphate or iron(III)-hydroxide polymaltose complex. On the basis of the measured compatibilities, iron(III)-hydroxide polymaltose complex can be administered orally simultaneously with many other drugs, without prejudicing the absorption of iron or of the other drug as is often seen with iron(II) and iron(III) salts. PMID- 2222550 TI - Pharmacokinetic evaluation of conventional and controlled release dosage form of propranolol. AB - A comparative pharmacokinetic study of a new controlled release multiple unit propranolol formulation and a conventional propranolol tablet was carried out in twelve healthy human volunteers in a randomized balanced crossover design. Under a single dosage regimen, subjects were administered either a single capsule containing controlled release propranolol equivalent to 160 mg of the drug or 80 mg of conventional propranolol tablet, twelve hourly. Peak plasma propranolol concentrations were low which occurred later after controlled release administration than after the administration of the conventional tablet. Analysis of the area under the plasma concentration-time curve (AUC) for the two formulations indicate no significant difference of bioavailability despite a prolonged absorption time and maintenance of effective plasma concentration for the controlled release preparation. PMID- 2222552 TI - Effect of gelatin infusions on blood serum lipid pattern. AB - The effect of gelatin infusions in rat on the various serum lipid constituents was studied by measuring the mean values of total lipids, lipoprotein lipase, triglycerides, phospholipids, cholesterol, non-esterified fatty acids, and lipoproteins. These measurements were made immediately following a single intravenous infusion of gelatin solution (1 ml/100 g body wt) and at different time intervals post-infusion. Repeated intravenous infusions of gelatin were also given to another group of rats and the above mentioned lipid constituents were measured 24 h after each dose. The results obtained showed that gelatin infusions have a definite hypolipemic effect. There was a significant reduction in the levels of total lipids, triglycerides, cholesterol, and B + preB/alpha ratios immediately following infusion and at 5, 24 and 48 h postinfusion. This reduction was transient and the values were gradually normalized at the end of the first week postinfusion. In rats receiving repeated i.v. infusions, the results obtained showed a significant decrease in the same lipid constituents during the whole month of gelatin administration. Values of lipoprotein lipase, lipid phosphorous and non-esterified fatty acids showed insignificant changes from baseline values at all time intervals following single and repeated i.v. infusions of gelatin solution. PMID- 2222553 TI - Variations of skin sensitivity to intracutaneous histamine provocations with regard to provocation time. AB - Dermal provocation tests with histamine and other mediators of allergy are widely used as diagnostic tools and as clinical pharmacological models. Diurnal variations of skin reactivity e.g. flare reactions have been postulated earlier. Potential differences in skin reactivity using histamine provoked flare areas as model were investigated by means of five different placebo formulations (i.v. solution; p.o. solution; p.o. solid forms). Flare reactions have been provoked every 3rd hour within a time span of 29 h using a cross-over design with an H1 antagonist positive control. No provocation was provided between 0:00 and 7:00 a.m. There was no statistically significant variation of skin reactivity with respect to provocation times under placebo treatment conditions. No dependence on plasmacortisol levels was observed. Interindividual differences in skin reactivity are more pronounced than the intraindividual variations. PMID- 2222555 TI - Rough sets approach to the analysis of the structure-activity relationship of quaternary imidazolium compounds. AB - The relationship between chemical structure and antimicrobial activity of 201 quaternary imidazolium compounds is analysed using the theory of rough sets. The compounds are described by 8 attributes concerning structure and are divided into 5 classes of activity. The description builds up on information system. Using the rough sets approach, first a minimum set of 4 attributes significant for a high quality of classification has been found. The analysis of distribution of values of significant attributes in the best and worst class led to the definition of typical representatives of best and worst compounds in terms of significant attributes. Finally, a decision algorithm has been driven from information system, showing important relations between structure and activity. It may be helpful in supporting decisions concerning the synthesis of new antimicrobial compounds. PMID- 2222554 TI - Synthesis and antimicrobial activities of some new tetrahydro-2H-1,3,5 thiadiazine-2-thione derivatives of amoxicillin. AB - A number of 6-[2-(dihydro-5-substituted-6-thioxo-2H-1,3,5-thiadiazine-3( 4H)-yl) 2-(4-hydroxyphenyl)acetamido]penicillanic acids has been synthesized as prodrugs by incorporating the amine group of amoxicillin trihydrate into tetrahydro-2H 1,3,5-thiadiazine-2-thione ring. The compounds have been prepared by the reaction of various alkyl or aralkyl amines with potassium hydroxide, carbon disulfide, formaldehyde and amoxicillin trihydrate. The structures of the compounds have been elucidated by UV, IR, 1H-NMR spectra and elementary analysis. The in vitro activity of these compounds against gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis), gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and yeast-like fungi (Candida albicans, C. parapsilosis, C. stellatoidea, C. pseudotropicalis) was investigated by the tube dilution method and compared with the activity of amoxicillin trihydrate. By this way their minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and minimal fungicidal concentration (MFC) values were determined. Compound I and Compound VII were significantly more effective than amoxicillin trihydrate against S. aureus (MBC: 6.25 micrograms/ml). Compound VI and Compound XI were effective against S. faecalis (MBC: 6.25 micrograms/ml) and Compound I and Compound VI were effective against E. coli (MBC: 12.5 micrograms/ml). All of the compounds and amoxicillin trihydrate were ineffective against P. aeruginosa (MIC: greater than 100 micrograms/ml). Compound IX and Compound X were the most active derivatives against yeast-like fungi; the MFC values for these compounds ranged between 6.25 and 37.5 micrograms/ml. PMID- 2222556 TI - Pharmacokinetics of 4-acetylaminophenylacetic acid. 1st communication: absorption, distribution, metabolism and excretion in mice, rats, dogs and monkeys after single administration of 14C-labeled compound. AB - Absorption, distribution, metabolism and excretion of 4-acetylaminophenylacetic acid (MS-932) were studied in mice, rats, dogs and monkeys after intravenous or oral administration of 5 or 10 mg/kg of 14C-MS-932. After the intravenous injection of 14C-MS-932, the radioactivity concentrations in the plasma decreased biexponentially. The half-lives of the elimination phase (t1/2, beta) were 2.58 h for mice, 2.35 h for rats, 1.88 h for dogs and 1.24 h for monkeys. After the oral administration of 14C-MS-932, the radioactivity concentrations in the plasma reached maximums between 0.4 and 1.3 h, thereafter decreasing with half-lives similar to those found for the intravenous injection. The systemic availability of this drug was 72-100% in all the species tested. No clear sex-related difference in radioactivity concentrations was found in rat plasma. After both intravenous and oral administrations, in all the species tested, almost all the radioactivity administered was excreted in the urine. Biliary excretion of radioactivity in bile duct-cannulated rats was only 1.42% of the intravenous dose over a 24-h period. Lymphatic absorption of radioactivity was negligible (0.2% of the dose over a 6-h period). After oral administration of 14C-MS-932, the radioactivity concentrations in the rat tissues tested reached maximums within 1 h, decreasing rapidly thereafter similar to the decrease in the concentration in the plasma. Much higher concentrations were present in the kidney and gastro intestinal tract than in the plasma, whereas the concentrations in the other tissues were lower. Results obtained by whole-body autoradiography were consistent with those obtained for the radioactivity in excised tissues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222558 TI - In vitro studies with the stabilized epoprostenol analogue taprostene. Effect on platelets and erythrocytes. AB - In vitro, the oxacyclic epoprostenol (prostacyclin) analogue taprostene like the native epoprostenol inhibited platelet aggregation and adhesion and induced deaggregation. Antiaggregatory action of taprostene was demonstrated towards arachidonic acid-, ADP-, thrombin- and norepinephrine-induced aggregations of human platelet rich plasma with IC50 values between 17 and 34 nmol/l. ADP-induced aggregations of human, dog or rabbit platelets were inhibited with an equivalent efficacy. Under the present conditions taprostene was about 3fold less active than epoprostenol. The deaggregatory effect, measured in arachidonic acid-induced aggregates of human PRP, could be detected only in concentrations from 1 mumol/l taprostene. The adhesion-inhibiting effect towards glass beads, measured in whole blood, appeared at comparable high concentrations (IC50 value: 2.4 mumol/l) and likewise the antihaemolytic effect on rat erythrocytes, which was exerted with a threshold concentration of 10 mumol/l. Heparin in a concentration range of 0.1 1000 micrograms/ml increased thrombocyte adhesion and this effect was prevented by 1 mumol/l taprostene. PMID- 2222557 TI - Pharmacokinetics of 4-acetylaminophenylacetic acid. 2nd communication: tissue accumulation and enzyme induction in rats after repeated administration, and placental and milk transfer after single dosing. AB - The absorption, distribution, metabolism and excretion of 14C-labeled 4 acetylaminophenylacetic acid (MS-932) were studied in male rats after administration of an oral dose of 10 mg/kg once a day for 21 days. Comparison with the single dosing showed no marked alterations in absorption, distribution, metabolism and excretion. There were no significant differences in the activities of hepatic aniline hydroxylase and aminopyrine N-demethylase between the MS-932 treated group (10 mg/kg for 8 days) and the 0.5% aqueous sodium carboxymethyl cellulose control group (p greater than 0.05). Placental transfer of radioactivity was studied after single oral administration of 10 mg/kg of 14C-MS 932 to pregnant rats on the 12-13th and 19-20th days of gestation. Radioactivity concentrations were highest in the maternal plasma and lowest in the amniotic fluid and fetus for both middle and late pregnancies. The concentrations in the amniotic fluid and fetus decreased more slowly than did the concentration in the maternal plasma. Excretion of radioactivity to milk was studied after single oral administration of 10 mg/kg of 14C-MS-932 to lactating rats on the 10th day after parturition. Radioactivity concentrations in the rat milk were maximal at 1 h after dosing and were lower than in the maternal plasma at all the sampling times. PMID- 2222559 TI - Pharmacokinetics of iopamidol in adults with renal failure. AB - The pharmacokinetics of iopamidol 370 (Iopamiro), a non-ionic water soluble organic iodine compound, were studied in adults with different degrees of chronic renal failure and in healthy volunteers. After 50 ml were administered i.v., plasma and urine levels were determined. The main pharmacokinetic parameters were calculated on the basis of bi-compartimental open model. There were significant differences from healthy volunteers in t1/2 beta, which increased with the degree of renal failure as the clearance values decreased. t1/2 beta was equal to 1.67 h in healthy volunteers, 4.24 h in patients with mild renal failure and 10.03 h in patients with severe renal failure. The clearance decreased as follows: 0.11 (l/h kg) in healthy volunteers, 0.06 (l/h kg) in patients with mild renal failure and 0.02 (l/h kg) in patients with severe renal failure. No significant differences were found in distribution volume values nor in t1/2 alpha. PMID- 2222560 TI - Safety aspects in biotechnology. Classifications and safety precautions for handling of biological agents. AB - The term "biotechnology" is today used much more widely than 10 years ago. According to the modern definition, biotechnology represents the "conveyor belt" which brings advances in the fields of molecular biology, cell biology, molecular genetics, microbiology, biochemistry and process engineering, etc., into the areas of application. It is attempted to indicate the development of safety standards concerning biotechnology. This development is in a state of flux, and the finding that the risks in handling r-DNA organisms are not larger than those arising when handling the known pathogens is becoming more accepted. Accordingly, these r-DNA organisms can also be classified into the known risk groups I-IV and handled under the corresponding safety conditions according to this classification: In the laboratory under the laboratory safety measures L1-L4 described in the BMFT-Guidelines or guidelines for occupational health and hygiene (UVV Biotechnologie) and on a process scale under the process safety measures described in the OECD report. The discussion of aspects on waste disposal, education/training and public perception in the field of biological safety completes the report. PMID- 2222561 TI - Medicare denials: should you appeal? PMID- 2222562 TI - The fragile X syndrome. PMID- 2222563 TI - Sex chromosomal abnormalities. Etiology, phenotypic expression, and the role of lyonization. AB - Individuals with sex chromosomal abnormalities have significantly better chances of leading normal lives than individuals with autosomal abnormalities. This is due, in part, to the role of lyonization in the genetic inactivation of X chromosomes. In contrast to earlier studies contaminated with subject ascertainment bias, prospective studies of individuals with SCA generally indicate a relatively normal profile with respect to overall intellectual capacity and psychopathology. Although some SCAs affect neuromotor, speech, language, cognitive and emotional development to some degree, it is noteworthy that none of the effects necessarily occurs and that some of the deficits are amenable to corrective intervention. Results from prospective studies also indicate significant genotype-environment interactions that can have important implications for intervention. PMID- 2222564 TI - Prevention of chromosomal disorders. Roles for clinicians. PMID- 2222565 TI - Fragile X syndrome. PMID- 2222566 TI - Recommended guidelines for infant hearing screening: analysis. AB - This paper has identified problems with the guidelines and the disadvantages of the ASHA protocol. Some of these are significant. Others are less important but represent issues that should be considered when designing an EID protocol. The problems and disadvantages are summarized below. 1. The guidelines should have estimated and cost and performance of the recommended protocol. 2. The guidelines should have identified the true advantage of ABR screening (lower cost) and the disadvantage (lower hit rate) as compared to other protocols. 3. The guidelines should have evaluated other possible protocols. 4. The guidelines recommended the same protocol for all facilities (with adequate resources) independent of local factors. 5. The guidelines recommended the same screening strategy for the ICN and the WBN when different protocols may be appropriate. 6. The guidelines reject ABR screening of all WBN infants as too expensive without estimates of cost. More importantly, this is a decision that should be made by local institutions or governments. 7. The screening protocol was developed without a detailed description of the diagnostic component of the EID protocol. 8. The guidelines should have provided more information to hospitals that do not have the resources necessary to implement the recommended protocol. 9. The recommended protocol requires significant in-patient testing that can cause problems with reimbursement. 10. Some infants at risk for progressive loss can be lost from follow-up. Apparently, the guidelines were developed using a subjective, experiential approach. Although clinical experience is important, subjective impressions can be subject to bias and error. Some type of quantitative analysis is essential when developing test protocols. Perhaps a more rigorous theoretical foundation is needed to focus research and guide the development of EID protocols. The ASHA protocol is reasonable, but there is little evidence indicating that it is superior to, or even as good as, other possible protocols. Like all protocols, it has advantages and disadvantages. That is not to say that all possible protocols are appropriate. For example, protocols that delay diagnostic testing beyond 6 months should be rejected if the goal is habilitation by 6 months. Protocols that use screening tests with extremely poor hit rates may be undesirable in most situations. There remains one fundamental question. Is it even appropriate to recommend a particular protocol when, by necessity, many important local factors must be ignored? Perhaps it would be better to provide the basic data and techniques that would permit audiologists to design EID protocols that are optimum for their own circumstances. PMID- 2222567 TI - Guidelines for the delivery of speech-language pathology and audiology services in home care. AB - Due to changing demographics, consumer preference, and priorities of the total health care delivery system, home care services are increasingly vital to the safety, well-being, and quality of life of many people. Consequently, the number of persons who need home-based speech-language pathology and audiology services is increasing. These guidelines cover the professional service components and related aspects of the home care model. It is ASHA's position that home-based speech-language pathology and audiology services should be conducted by certified (and licensed where applicable) speech-language pathologists and audiologists, or by individuals who meet the educational requirements for certification and are receiving the supervised experience required for certification (Asha, 1981). These guidelines have been formulated to assist the speech-language pathologist and audiologist providing services in the unique environment of the home. The intent of these guidelines is to facilitate integration of services, cost effectiveness and quality of client care. PMID- 2222568 TI - Endocrine consequences of alcohol abuse. AB - The recognized endocrine consequences of alcohol abuse are reviewed on an organ by organ basis. The organ systems for which the most information is available (liver, heart, brain) are presented first followed by those where the information base is less. PMID- 2222569 TI - Alcohol and bone disease. AB - Alcohol is considered to be an important risk factor for various bone diseases but recent studies have shown that moderate alcohol intake can be beneficial to bone structure. Alcohol decreases osteoblastic activity, leading to decreased bone formation and defective mineralization. The changes reported in calciotropic hormones, mainly vitamin D and parathyroid hormone, are observed due in part to a deficient intestinal absorption of vitamin D and an inadequate synthesis of its hepatic metabolite, although greater emphasis has been given to dietary deficiencies or lack of exposure to sun. The changes in parathyroid hormone are not consistent and since there is no greater incidence of hyperparathyroidism in alcoholic patients, it suggests that alcohol does not have a long-term effect on the parathyroid glands. Alcohol increases calcitonin secretion acutely; calcitonin is an inhibitor of bone resorption and may be the mechanism by which moderate alcohol intake protects bone structure. Alcohol increases urinary calcium, magnesium and zinc excretion. Zinc deficiency has been postulated as a cause of oesteoporisis because it causes hypogonadism. The decrease in the levels of the gonadal hormones and the increase of cortisol, observed in chronic alcoholics, may indirectly cause osteopenia and aseptic necrosis. To these actions must be added the acidosis due to alcohol and the greater tendency of the alcoholic to fall, all of which influence bone changes and increase the incidence of bone fractures. PMID- 2222570 TI - T cell subsets (Tc, Th, Ts, Tsi) and IL2 receptor-bearing cells in peripheral blood of patients in the acute phase of alcoholic hepatitis. AB - The present study was designed to evaluate the proportion of T cell subsets and IL2 receptor positive cells in the peripheral blood of patients with acute alcoholic hepatitis (AAH) using monoclonal antibodies to T cell antigens and Tac in a double immunofluorescent technique. The results indicate that the percentage of the total T cells and the intensity of all the T cell antigens are significantly reduced and the percentage of T helper cells and the ratio between Th/Ts cells are significantly increased in AAH when compared to healthy controls. But, significant differences in values observed in this study were not found for the absolute number of these cells. These altered values returned to normal levels during convalescence. PMID- 2222571 TI - Estimation of the amount of alcohol ingested from a single blood alcohol concentration. AB - Capillary blood alcohol concentrations (BAL) measured in 22 young adult male volunteers each of whom received three different treatments of alcohol (total N = 66) have been related quantitatively to the dose of alcohol ingested. Linear regression with reasonably homogeneous variances have been found when the BAL at 2, 2.5 and 3 hr are divided by the person's body weight and plotted versus the g/kg (D/W) dose. Error analysis indicated that the least error in the predicted dose (D/W) was obtained for BAL measured at 2 hr post dosing. In the latter case the mean absolute error was 6.23%, 59% of the errors were within +/- 5% and 88% of the errors were within +/- 10%. PMID- 2222573 TI - Ethanol-inducible cytochrome P-450 activity and increase in acetaldehyde bound to microsomes after chronic administration of acetaldehyde or ethanol. AB - Chronic ethanol consumption results in acetaldehyde adduct formation with proteins such as haemoglobin and liver proteins in vivo. Our purpose was to study the binding of acetaldehyde to liver microsomal proteins, a site of ethanol oxidation via cytochrome P-450 (especially P-450 II E1), after chronic administration of ethanol or acetaldehyde for 21 days to rats. The liver microsomal oxidation of 1-butanol by the ethanol-inducible P-450 also was examined. Acetaldehyde bound to liver microsomal proteins was higher in ethanol fed rats compared with acetaldehyde-treated rats (0.735 vs 0.413 nmol/mg of protein respectively). The biotransformation of n-butanol to butyraldehyde by liver microsomes was increased (by 136%) in ethanol-fed rats vs controls, whereas in acetaldehyde-treated rats this increase was much lower (only 27%). However, in this last group, a significant negative relationship between the quantity of acetaldehyde bound to microsomal proteins and the monooxygenase-catalyzed transformation of butanol by liver microsomes was demonstrated (r = -0.79, P less than 0.01). These results suggest that proteins of liver microsomes are a target for acetaldehyde binding during ethanol oxidation and such adduct formation could impair the oxidative properties of the alcohol-inducible cytochrome P-450. PMID- 2222572 TI - Studies with cDNA probes on the in vivo effect of ethanol on expression of the genes of alcohol metabolism. AB - Mice (Mus musculus) from three genetic strains with variable responses to ethanol challenge (BALB/c, C57BL/6J and 129/ReJ) were used to evaluate the effect of ethanol feeding on hepatic mRNA specific to the two primary enzymes of ethanol metabolism; alcohol dehydrogenase (ADH; E.C. 1.1.1.1) and aldehyde dehydrogenase (ALDH; E.C. 1.2.1.3). Adh-1 (ADH) and Ahd-2 (ALDH) specific mRNA were evaluated on the livers of ethanol-fed mice and from their age, sex and genotype matched controls (using an isocaloric liquid diet). C57BL/6J (alcohol resistant) mice show a significant (approx. 200%) increase in ADH-1 mRNA levels after ethanol treatment, compared to their matched controls. BALB/c (alcohol sensitive) mice have approximately a 20% increase with ethanol treatment while 129/ReJ (alcohol sensitive) mice show a slight reduction in the ADH-1 specific mRNA following ethanol feeding. A strain-specific pattern is also apparent in the AHD-2 mRNA as a result of ethanol feeding in the experimental animals. C57BL/6J mice have an increase and BALB/c mice show no apparent change in the AHD-2 mRNA. 129/ReJ mice fed an ethanol diet, on the other hand, appear to have a decrease in the level of AHD-2 hepatic mRNA as compared to their matched controls. The relative mRNA levels of the two genes correlate well with the respective enzyme activity levels, but for mice on the control diet only. Ethanol feeding, which causes an apparent reduction in hepatic ADH enzyme activity in BALB/c and 129/ReJ and an apparent increase in ALDH activity in C57BL/6J (under the experimental protocols used) also alters the mRNA levels specific to the two genes. However, changes in the mRNA levels after ethanol feeding cannot be directly related to the changes seen in enzyme activity. The observed steady state level of AHD-2 mRNA and the increase in ALDH activity after ethanol feeding, which is unique to C57BL/6J mice, is expected to offer a faster clearance (metabolism) of acetaldehyde, the toxic metabolite, and may be responsible for, or contribute to, the relative resistance of this strain to ethanol. PMID- 2222575 TI - The effect of maternal ethanol infusion on placental blood flow and fetal glucose metabolism in sheep. AB - Intravenous infusion of 1 g ethanol/min over 1 hr to seven catheterised pregnant ewes decreased blood flow on both sides of the placenta. The reductions in blood flow were maintained for at least 2 hr after the infusion of ethanol had ceased. Although blood flow was reduced, fetal blood gases were unchanged. Plasma glucose concentrations were unchanged by ethanol, but fetal glucose supply and consumption were both decreased following maternal ethanol infusions. If maintained by chronic alcohol consumption these changes could contribute to the growth retardation seen in the Fetal Alcohol Syndrome. PMID- 2222574 TI - The effect of interrupted alcohol supply on spontaneous alcohol consumption by rhesus monkeys. AB - The alcohol supply (a 16% and a 32%, v/v, ethanol-in-water solution) for eight male rhesus monkeys, who already have had free access to water and ethanol solutions concurrently for about one year, was interrupted for 1, 2 or 7 days. The previously acquired ethanol consuming behaviour appeared very resistant to extinction, because ethanol consumption was immediately resumed after renewed access, even at a temporarily increased level. Since physical withdrawal distress was not observed and the increase was higher when interruption lasted longer, the observed behaviour could be attributed to the reinforcing effects of ethanol, leading to specific ethanol-directed behaviour. PMID- 2222576 TI - Attenuation of effects of phenylethylamine on social and individual behaviour in mice by ethanol pretreatment. AB - Beta-phenylethylamine (PEA, 10 mg/kg, intraperitoneally) exerts the following behavioural effects in mice: (1) a decrease in the rate and duration of contacts (sniffings), typical of anxiogens, in albino SHR (bred from Swiss) male mice and a decrease in the duration of contacts in C57l/6 mice; (2) a decrease in the duration of grooming in both strains; (3) an increase in locomotion and rearings in long-sleeping C57Bl/6 mice. Pretreatment with ethanol (100 mg/kg, orally) diminished these effects of PEA. It is suggested that the anxiolytic action of ethanol may be related to its antagonism of PEA. PMID- 2222577 TI - Alcohol use and depressive symptoms among Mexican Americans and non-Hispanic Whites. AB - Alcohol use is associated with depressive symptoms in several studies. Using data from a community survey, this study examined whether this relationship (a) can be accounted for by ethnic or sociodemographic differences among persons who engage in various levels of alcohol use; and (b) differs for Mexican Americans (N = 1244) and non-Hispanic Whites (N = 1149). Using large quantities of alcohol, and, among men, daily drinking, were associated with depressed mood. These associations were similar for Mexican Americans and non-Hispanic Whites, and associations of quantity and frequency with depression were independent of each other. Among women, the cultural and demographic characteristics of high-quantity drinkers and abstainers (both of whom tended to be Mexican Americans) accounted for the association of alcohol use with depression. Among men, there was some suggestion that unemployment and unmarried status mediated the association of alcohol quantity with depression. People who drank greater quantities of alcohol per occasion reported more somatic depressive symptoms, and more frequent male drinkers reported more of most types of depressive symptoms. PMID- 2222579 TI - Trauma prevention: puzzlement or possibility? PMID- 2222578 TI - Is the Lieber-DeCarli liquid ethanol diet adequate in vitamin E? PMID- 2222580 TI - Trauma in the workplace. An overview. AB - To attenuate the incidence of occupational deaths and injuries, which occur at a rate of approximately 25 deaths and 10,000 injuries daily, occupational health nurses must focus on injury control for the entire population of workers. Knowledge of the mechanics of injury and populations at risk for various types and severities of injuries is essential to developing injury prevention programs and appropriately responding to emergent injuries. The lack of a comprehensive and reliable surveillance method has been described as a major obstacle in evaluating the occupational injury problem, as well as measuring progress toward achievement of the 1990 Objectives in Occupational Safety and Health. Variations in the estimates have been attributed to different methodologies used in collecting surveillance data, including diverse definitions, inclusion criteria, and data sources. Lost workdays due to injuries reported for 1983 cost an estimated $33.4 billion in direct and indirect costs. Mining, construction, agriculture, and transportation are the most hazardous industries in terms of both fatalities and injuries. Activities appropriate for the occupational health nurse in preventing injury include retrospective analysis of injury patterns and costs, proactive inspection of the workplace for high risk factors, preplacement screening of workers, ergonomic analysis of jobs, evaluation of the type and use of personal protective equipment, provision of safety training, and collaboration with other agents of the firm in evaluating and designing injury reduction strategies and disaster plans. PMID- 2222582 TI - Traumatic amputation. Mechanisms of injury, treatment, and rehabilitation. AB - Traumatic amputations are one of many injuries that can occur to the body's musculoskeletal systems. Degloving, partial and total amputations are common types of traumatic injuries. Since traumatic amputations are very life threatening, emergency treatment must be initiated quickly and directed toward profuse blood loss and potential hypovolemia. Not only do traumatic amputees undergo extreme physiological changes, but they must also encounter the psychological trauma of an amputation. Due to a loss of body part(s) and alteration in body image, the amputee often experiences the stages of grieving which may take months and years to resolve. Extensive rehabilitation with the use of an interdisciplinary team approach is one of the most successful ways to return the amputee to the work place. A combination of occupational therapy, physical therapy, vocational rehabilitation and psychological support generally promote a sense of well being and return the traumatic amputee to a level of independence. PMID- 2222581 TI - Trauma: the acute response. AB - Moderate to severe trauma is followed by a local response, which involves changes in cell function and an inflammatory reaction, and a systemic response coordinated by the nervous and endocrine systems. Early post-trauma alterations in cells are due primarily to decreased oxygen supply and include 1) the shifting of electrolytes and water, either into or out of cells, and 2) the production or release of various local tissue factors. These tissue factors produce changes in blood flow, increased vascular permeability, and other local manifestations of inflammation. Trauma activates nervous and hormonal pathways which help to restore blood volume and maintain the function of essential organs. The effects of these responses on cellular oxygen consumption and body temperature are described. Examples of respiratory system involvement in response to trauma in the lungs or elsewhere are given. These include increased capillary permeability in the lungs, pulmonary emboli, and damage from smoke and heat inhalation. PMID- 2222583 TI - Eye trauma in the workplace. AB - A baseline visual acuity should be on record for medical and legal purposes. Identifying an eye injury and referring the person for appropriate treatment can save vision. Immediate eye irrigation in the case of chemical burns can substantially decrease the possibility of permanent vision damage. PMID- 2222584 TI - Thermal injuries in the workplace. AB - Regardless of mechanism of injury, stop the burning process, assess the cardiopulmonary function, remove appropriate clothing and jewelry, and cool the burned area with tepid water. With a dry chemical, wipe off as much of a chemical as possible before beginning irrigation. Persons giving first aid must protect their own skin from contact with the chemical. All significant burns should be referred to a physician skilled in burn treatment. Occupational health nurses should join together and create a national tool to report all work related thermal injuries. PMID- 2222585 TI - Head injury in the workplace. AB - Work related head injuries do not occur frequently in comparison to other injuries, but their importance lies in their relative severity, both in terms of work days lost and long term morbidity, making it important for the occupational health nurse to have knowledge of how to deal with the initial injury and residual problems. In head injury, most of the treatment is aimed toward prevention of hypoxia, airway obstruction, hypercapnia, hypotension, and bleeding. The Glasgow Coma Scale is used for the severely head injured person. The residual cognitive impairment, emotional disturbances, and behavioral changes after head injury tend to continue long after the physical disabilities have resolved. Therefore, the occupational health nurse needs to assist recovering individuals and their families and coworkers to learn to cope with physical, cognitive, behavioral, and intellectual deficits. PMID- 2222586 TI - The question and the answer. Part 1: Levels of research questions. PMID- 2222587 TI - Using information to optimize case management. PMID- 2222588 TI - Rapid thawing of fresh frozen plasma in two-liter bags. AB - The authors hypothesized that plasma could be rapidly thawed in two-liter Transfer Pack Units, because of their greater surface area (993 cm2) compared to standard satellite bags (348 cm2) of Blood Pack Units (both from Fenwal, Baxter Healthcare Corp, Deerfield, IL). Five units of FFP were prepared in each bag. The Sterile Connection Device (DuPont, Wilmington, DE) was used to transfer plasma from the satellite to transfer pack units, and these were put in metal canisters before all units were frozen at -65 degrees C. Thawing time was 4.8 +/- 1.3 (SD) minutes and 15 +/- 3.2 (SD) min. for units prepared in modified and standard methods respectively (t = 6.33, P less than .01). The thermal rate constants were calculated as 0.0034 and 0.0033 for the two methods. The finding of similar values substantiate the theory that thawing time is related to the volume to surface area ratio. PMID- 2222590 TI - Bretylium tosylate versus lidocaine in experimental cardiac arrest. AB - Bretylium tosylate has been shown effective in the treatment of ventricular fibrillation and in the prevention of its recurrence. However, lidocaine is generally preferred because bretylium could have adverse hemodynamic effects related to its antiadrenergic action. To explore further the differences between these two antiarrhythmic agents, the authors compared the effects of bretylium, lidocaine, and saline on a standardized dog model of ventricular fibrillation followed by electromechanical dissociation (EMD). The protocol included three successive episodes of cardiac arrest in each animal. Three minutes before each episode of ventricular fibrillation, 5 mg/kg of bretylium tosylate (n = 11), 1 mg/kg of lidocaine (n = 9) or saline (n = 12) were administered blindly. There was no difference in the duration of cardiac arrest (bretylium, 8 min 18 sec; lidocaine, 7 min 54 sec; saline, 8 min 20 sec) or the total doses of epinephrine required to resuscitate the animals. Both bretylium and lidocaine appeared to preserve cardiac function 5 minutes after recovery, as stroke volume increased from 17.8 +/- 6.7 to 18.7 +/- 6.7 mL (NS) after bretylium and from 17.7 +/- 7.7 to 19.0 +/- 7.0 mL (NS) after lidocaine, but decreased from 19.0 +/- 5.3 to 14.6 +/- 6.0 mL (P less than .05) after saline. During the first 10 minutes of EMD, ventricular fibrillation or ventricular tachycardia recurred in 4 dogs treated with lidocaine, 3 dogs treated with saline, but no dog treated with bretylium (P less than .05 between bretylium and saline).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222589 TI - Controlling for the severity of injuries in emergency medicine research. AB - The injury severity score (ISS) and age have been used retrospectively to control for trauma severity. Other control variables such as the revised trauma score (RTS) and the TRISS method (which estimates the probability of survival for each patient) additionally require that values of blood pressure, Glasgow coma scale, and respiratory rate, be recorded in the emergency department. The authors question when the RTS, ISS, the ISS and age, or the probability of survival calculated using the TRISS method should be used to control for severity of injuries in trauma research. Relations between predictor variables and (1) survival to hospital discharge, (2) hospital length of stay for survivors, and (3) length of ICU stay were compared by cause of injury: penetrating, motor vehicle accident, low fall, or other blunt. Data were collected over 12 months for 2,914 consecutive adult patients who died or stayed in five nontrauma and three trauma centers for 48 hours or more. For survival, the false-negative rates of probability of survival calculated using the TRISS method were approximately half that of the ISS and age; no variable adequately explained survival among those with low falls. Combinations of ISS, RTS, and age explained the most variation in lengths of hospital stay among survivors, while ISS explained the most variation in lengths of intensive care unit (ICU) stay. Researchers should consider the ISS with RTS and age to control for severity when lengths of hospital or ICU stay are studied. The TRISS method should be used in studies of survival. In both cases, the RTS which requires data collection in the emergency department must be calculated. PMID- 2222591 TI - Urgent care center pediatric telephone advice. AB - Pediatric telephone advice is sought frequently by members of the community. This study was undertaken to evaluate the quality and accuracy of pediatric telephone advice given by free-standing urgent care centers. One hundred such facilities were telephoned and advice was requested by a research assistant. A case was presented that could have represented a pediatric medical emergency. Overall only 17 centers gave adequate advice. The data suggest that under some circumstances free-standing urgent care center pediatric telephone advice may be inaccurate and inappropriate. Workable policies and protocols for pediatric telephone advice should be instituted by these facilities. PMID- 2222592 TI - Cardiopulmonary resuscitation skills retention in family members of cardiac patients. AB - The purpose of this study was to determine if the use of a retention strategy would maintain cardiopulmonary resuscitation (CPR) skills in family members of cardiac patients. Thirty-one subjects trained in CPR received retention packets 3 and 6 months after CPR training. Sixteen subjects were tested for CPR retention at 7 months after initial training, and 15 at 12 months. Likelihood chi 2 was used to compare the 7- and 12-month groups. There were no differences between the 7- and 12-month groups, because CPR retention overall was poor. Only 19.4% of subjects reported using the retention packet; therefore, subjects were regrouped into practice and no practice groups for purposes of further statistical analysis. There were significant differences in retention in subjects who practiced compared with subjects who did not. These findings underscore the importance of promoting practice/review after initial CPR training for family members of cardiac patients. PMID- 2222593 TI - What is the optimal volume of administration for endobronchial drugs? AB - During general anesthesia, three groups of six patients each received 2 mg/kg lidocaine as a marker substance endobronchially in either 10, 5, or 3 mL distilled water. It was found that the group receiving 10 mL initially exhibited the highest lidocaine plasma concentration with a mean of 2.01 micrograms/mL, in comparison with 1.25 micrograms/mL in the 5 mL group and 0.95 micrograms/mL in the 3 mL group. After about 10 minutes, concentration courses were almost the same in the 10 mL and the 5 mL groups. The PaO2 in the 10 mL group dropped initially by approximately 40 mm Hg on average and remained low over 60 minutes. By this time the PaO2 in the 5 mL group (initial drop 46 mm Hg) had come back to the original value (P less than .05). The 3 mL group exhibited even more favorable courses in the PaO2 (initial drop 16 mm Hg on average). However, the lidocaine plasma concentration was at the lowest at all times in this group and, moreover, under the therapeutic level of 1.5 micrograms/mL with the dosage used. PMID- 2222594 TI - Patients who initially refuse prehospital evaluation and/or therapy. AB - The authors performed a retrospective descriptive and analytical cohort study of prehospital patient initial refusal of care (PIRC) cases to characterize the types of patients encountered and to assess factors associated with their dispositions. During a 6-month period, 169 of 1715 (9.9%) base station calls in an urban emergency medical service (EMS) system were for physician involvement in a PIRC. Patients' dispositions were as follows: left at scene against medical advice (53%); taken by ambulance to the hospital (28%); left with friend (13%); other disposition (5%). While police were called to the scene 41 times, they placed a "legal hold" on only 10 patients. Leaving the patient at the scene against medical advice was associated (logistic regression analysis; P less than .05) with the absence of the following factors: family on the scene and a police hold, and with the presence of the following factors: treated hypoglycemia, alcohol use, orientation, and normal speech. The development of statutes that allow police hold placement under the guidance of the base station physician may be necessary. Such statutes would aid transportation of a patient considered by EMS personnel to have impaired mental capacity that may limit the patient's ability to understand medical care decisions. PMID- 2222595 TI - A controlled trial of nebulized isoetharine in the prehospital treatment of acute asthma. AB - Acute asthma is a potentially life-threatening disorder, recognizable to the prehospital care provider. While therapies are available to the prehospital care provider for treating acute asthma, no previous controlled studies have been performed demonstrating the treatment in the field is efficacious and safe. The authors conducted a controlled trial of the prehospital use of nebulized isoetharine in an urban emergency medical services system. Fifty-two patients with acute asthma were studied. Patients were initially evaluated with a peak flow meter. Half of the patients received isoetharine, while the control group received basic life support only. There was no difference in baseline values. Peak expiratory flow increased from 138 L/min to 148 L/min in the control group, while it increased from 149 L/min to 218 L/min in the treatment group (P less than .001). The authors conclude that paramedic treatment of acute asthma with nebulized isoetharine is effective in improving pulmonary function and clinical status during transport. PMID- 2222596 TI - Ectopic pregnancy: ten common pitfalls in diagnosis. AB - Ectopic pregnancy (EP) is a common, life-threatening complication of pregnancy. Modern technology (ultrasonography and improved pregnancy tests) should facilitate the diagnosis of EP. However, in a retrospective review of 65 cases of confirmed EP managed over 18 months at an urban teaching hospital, only 37 of 65 patients (57%, Cl95 = 44%, 69%) received prompt diagnosis and treatment; delays occurred in 28 patients (43%). In 10 of the 27 delayed cases, the diagnosis of EP was not even considered at the time of the first visit. In patients with a delayed diagnosis, morbidity (transfusions, cardiovascular instability, progression of illness) did occur. Diagnostic pitfalls that resulted in delayed care were reviewed, delays most commonly occurred in patients with a benign examination or "atypical" pain. Risk factors for EP were missed (7 patients, 25%), subtle clues to blood loss were often ignored (10 patients, 36%), and passage of tissue was thought to exclude EP (2 patients). Ultrasound was only helpful for half of the diagnoses and was misinterpreted in 27%. A dry or serous culdocentesis occurred frequently. In five patients, a falling or low quantitative human chorionic gonadotropin level was believed to indicate a completed abortion. The authors conclude that almost half of EPs are still missed on the first physician visit; errors and pitfalls in diagnosis are still common in the 1980s. PMID- 2222597 TI - Whole bowel irrigation and the cocaine body-packer: a new approach to a common problem. AB - Gastrointestinal drug smuggling is a common problem in many major cities. Though the majority of cases never require medical attention, the "body-packer" frequently presents with life-threatening symptoms of intoxication, including seizures and cardiorespiratory collapse, as well as mechanical obstruction from the ingested drug packets. The risk to asymptomatic smugglers may vary with packaging materials, and remains unknown. Lack of controlled studies, and variations in packaging materials and clinical outcomes have prevented formulation of a consistent management strategy. Current recommendations for asymptomatic body-packers vary from immediate surgical removal, to use of laxatives, to observation. The authors present the first reported case of an asymptomatic cocaine body-packer treated with whole bowel irrigation with polyethylene glycol electrolyte lavage solution. This strategy was safe, well tolerated, resulted in the rapid elimination of drug packets from the gastrointestinal tract, and facilitated assessment by contrast radiography. The potential benefits and limitations for the use of whole bowel irrigation in this difficult problem are discussed. PMID- 2222598 TI - The spectrum of emergency care of agricultural trauma in central Wisconsin. AB - Agriculture is among the most dangerous occupations in the United States. When injuries do occur, the emergency department (ED) is the primary source of care. Over a 2-year period, the emergency medicine section of the Marshfield Clinic/St Joseph's Hospital, cared for 913 victims of agricultural trauma. Although 11% were initially admitted and 4% were later treated, the remainder received their care solely in the ED. Unlike most occupational injuries, people of any age may be involved in agricultural injuries; 27% in this series were less than 18 years of age and 5% were 65 years or older. Just over half of all injuries were from mechanical devices, including tractor and farm machinery. The remainder were from animals, falls, or exposure. Although several different types of injuries occurred, the most common diagnoses were soft tissue injuries and fractures and the most common procedure was diagnostic radiography followed by wound and fracture care. An ED in a rural setting should be prepared to deal with agricultural trauma. PMID- 2222599 TI - Atrial fibrillation with cardiac tamponade as the initial manifestation of malignant pericarditis. AB - This article describes the case of a 72-year-old woman with cardiac tamponade and atrial fibrillation as the initial manifestation of a lymphoid malignancy. The pathogenesis of cardiac tamponade, various diagnostic modalities, and therapy of this condition are reviewed. PMID- 2222600 TI - Methylene chloride: report of five exposures and two deaths. AB - Five patients presented to the emergency department (ED) following exposure in an enclosed space to methylene chloride (dichloromethane), used for removing paint. Two workers and three rescuers were involved. Two rescuers complained only of dizziness and mild nausea, and were subsequently discharged from the ED. One rescuer was asymptomatic. Worker no. 1 arrived in cardiac arrest and eventually died in the ED despite resuscitation efforts. Worker no. 2 also presented to the ED in cardiac arrest, and was successfully resuscitated to pulse and blood pressure. However, he never regained consciousness or spontaneous respirations, and died on the fourth day. Of interest is that worker no. 2's carboxyhemoglobin level increased from 2% to 8% over the 9 hours following admission, despite administration of 40% to 50% oxygen by endotracheal tube. Among the conclusions that can be drawn are (1) the cause of death in these patients was not carbon monoxide poisoning, but solvent-induced narcosis; (2) carboxyhemoglobin levels may continue to rise following cessation of exposure, despite administration of high flow oxygen; (3) rescuers can easily become victims if proper protective clothing and respirators are not worn. PMID- 2222601 TI - Epidural hematoma: an unusual presentation. AB - The authors present a patient with a traumatic epidural hematoma who complained only of headache and presented to the emergency department 48 hours after a fall. Mental status and neurological examination were normal. This delayed presentation is more commonly seen when a subdural hematoma is present but may result from epidural bleeding. Delayed formation of a traumatic epidural hematoma may occur when the following are present: elevated intracranial pressure, hypovolemic shock, a concomitant mass lesion, coagulopathy, bleeding from dural or diploic veins, a dural sinus laceration, a traumatic pseudoaneurysm, or an arteriovenous fistula. Although criteria for computed tomography of patients with head injuries remain variable in the literature, delayed presentation of epidural bleeding must be considered in the differential diagnosis of posttraumatic headache irregardless of the time interval or neurological presentation. PMID- 2222602 TI - Buccal cellulitis. AB - Buccal cellulitis (BC) is an innocuous appearing infection of the cheek that is found in children and has a high incidence of concomitant bacteremia. Typically, the child is younger than 12 months and has a 2 to 8 hour prodrome of coryza and fever before developing the cellulitis on the cheek. A purplish hue on the cellulitic region is highly suggestive of Hemophilus influenzae bacteremia. The differential diagnosis is reviewed. A complete blood count, blood culture, and cellulitis aspirate culture, should be obtained on all patients with BC. Meningitis may be present despite the lack of meningeal signs. A lumbar puncture should be performed on all children at risk for bacteremic BC. The vast majority of these children are bacteremic and require parenteral antibiotics. A typical case of BC is presented and its management is reviewed. PMID- 2222603 TI - Near fatal subacute thallium poisoning necessitating prolonged mechanical ventilation. AB - The authors describe a case of severe sensory-motor polyneuropathy caused by subacute thallium-intoxication rapidly progressing to respiratory failure due to complete muscle paralysis. After more than 2 months of mechanical ventilation, weaning from the ventilator was possible. Further intensive physical rehabilitation required an additional 6 months hospital stay, and 18 months later, neurological recovery was complete except for the distal lower limbs muscles. The authors discuss the different forms of thallotoxicosis and the present treatment is reviewed. Maximal prolonged therapeutic support should be offered in severe thallotoxicosis because of possible near complete recovery. PMID- 2222605 TI - Is gut emptying all washed up? PMID- 2222604 TI - Critical care transportation medicine: new concepts in pretransport stabilization of the critically ill patient. AB - Regionalization of health care for trauma has become commonplace, and the same concept for critically ill medical/surgical patients is developing. Recent evidence suggests that current stabilization measures used by transport teams can be inadequate for this critically ill patient population. In trauma, speed has been considered a necessity to get the patient to a facility which cannot be carried out to the field, eg, an operating room. For acute medical illnesses, critical care transport teams can bring intensive care technology to the patient. Accumulating evidence supports the premise that speed of transport is not as important as stabilization before transport, knowledge of hemodynamics during transport, and early use of critical care monitoring systems. Other reports identify the need for initial evaluation and stabilization of critically ill patients by physicians at the critical care level of expertise. Accordingly, critical care transportation teams have evolved, creating new notions of pretransport stabilization not applicable to previous transport systems. PMID- 2222606 TI - Computer-assisted medical charting in the emergency department. PMID- 2222607 TI - Up in smoke: the MAST garment fuels more fires. PMID- 2222608 TI - Anaplastic astrocytoma in association with human immunodeficiency virus type 1 infection. PMID- 2222609 TI - B(n)ite of the iguana. PMID- 2222610 TI - Unilateral pharmacologic mydriasis secondary to crack cocaine. PMID- 2222611 TI - Spontaneous migration of an intraspinal bullet following a gunshot wound. PMID- 2222612 TI - Salt poisoning in a two-year-old child. PMID- 2222613 TI - The demand for emergency medicine residency graduates. PMID- 2222614 TI - Emergency medicine and critical care. PMID- 2222615 TI - Effects of gestational weight gain in morbidly obese women: II: Fetal morbidity. AB - Recommended gestational weight gain is based on supplying adequate nutrition to the conceptus, ensuring normal growth and development. Since morbidly obese women have an overabundance of nutrients for fetal transfer, we examined the effects of weight gain on fetal outcome in women greater than 160% of ideal body weight. Gestational weight gains varied from -18 to +64 pounds, allowing analysis of fetal outcome based on maternal weight gain. No correlation between maternal weight gain and ketonuria, birthweight or length, placental weight, or Apgar scores was noted. Gestational age at delivery was inversely related to weight gain. When grouped by maternal weight gain, fetal outcome was no different if mothers gained less than or greater than 10 pounds. We conclude that limited weight gain in the morbidly obese women does not adversely affect fetal outcome, and prospective trials of limited weight gain diets in morbidly obese women are warranted. PMID- 2222616 TI - Management of varicella pneumonia complicating pregnancy. AB - We report five cases of varicella pneumonia during pregnancy. Prompt diagnosis along with aggressive management, including antiviral chemotherapy and ventilatory support, may improve maternal and neonatal outcome. PMID- 2222617 TI - Home death and hospital follow-up of the dying infant. AB - As technology and medical care have improved, increasing numbers of critically ill neonatal patients are surviving the immediate neonatal period. The hectic environment of the neonatal intensive care unit often makes it difficult for personnel to attend adequately to the needs of the dying infant and his family. Accordingly, the option of home death for such infants has been offered in our neonatal intensive care unit. Experience is described for six infants who were managed in this manner. PMID- 2222618 TI - Intrauterine sound levels: intrapartum assessment with an intrauterine microphone. AB - The complex mechanisms responsible for fetal hearing are in place and functional by 26 weeks of gestation, but little is known about the acoustic milieu of the amniotic cavity. We placed an electrically isolated microphone in the uterus of nine term gravid volunteers after amniorrhexis. Baseline levels of intrauterine sound were 72 to 88 db. Transabdominal vibroacoustic stimulation with an artificial larynx produced peak mixed frequency sound levels of 91 to 111 db. We conclude that the term fetus in labor is exposed to physiologic sound levels higher than we had anticipated; the application of a quantifiable sound stimulus to the maternal abdominal wall results in a small increment in intrauterine sound; and within the limits specified, experimental fetal acoustic stimulation should pose no major risks. PMID- 2222619 TI - Maternal cigarette smoking during pregnancy, adiposity, social class, and perinatal outcome in Cardiff, Wales, 1965-1977. AB - There have been several reports in which maternal nutritional status has been implicated as either a mediating or moderating factor in the relationship between maternal cigarette smoking and birthweight and perinatal survival. Also, there is evidence that the effects of maternal cigarette smoking on both intrauterine growth and fetal viability are more intense among women of lower social status. The well-maintained data set of the Cardiff Births Survey from 1965-1977 afforded an opportunity to review these issues among over 50,000 births in south Wales (the survey took place in Cardiff City through 1973 and subsequently included suburban areas of South Glamorgan). The major findings were: (1) Smoking was much more common with descending maternal social status; (2) among upper status women, smokers had similar or slightly greater mean Quetelet's indices (kg/m2) than nonsmokers. Among lower status women, smokers were considerably thinner than nonsmokers; (3) the greater the adiposity of the mother, the less the association between cigarette smoking and depressed birthweight; (4) perinatal mortality was significantly higher among heavy smokers (10 or more cigarettes a day) than among nonsmokers; and (5) neither the decrease in birthweight nor the excess mortality associated with smoking was greater among those of lower rather than upper social status, except among class I women, among whom smoking was only minimally associated with depressed birthweight. With the inclusion of the South Glamorgan suburban population in the survey after 1974, the excess mortality associated with heavy smoking dropped from 53 to 16%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222620 TI - Logothetopulos pack for the management of uncontrollable postpartum hemorrhage. AB - This is the first reported case in which a Logothetopulos pack was utilized to achieve pelvic hemostasis in a patient requiring a cesarean hysterectomy for placenta accreta with postpartum hemorrhage. The Logothetopulos pack is an easily constructed gauze tamponade method that proved to be life-saving in this case. PMID- 2222622 TI - Use of thiazide diuretics to reduce the hypercalciuria of hypoparathyroidism during pregnancy. AB - A pregnant patient with idiopathic hypoparathyroidism is presented. Her hypomagnesemic hypocalcemia was unresponsive to conventional therapy, or magnesium supplementation. Sodium restriction with thiazide therapy successfully reduced her renal calcium wastage to control her symptoms and raise her serum calcium levels. PMID- 2222623 TI - Sonographic findings in septo-optic dysplasia in the fetus and newborn infant. AB - A 28-year-old primigravida woman was referred for ultrasound studies at 27 weeks' gestation. Sonographic examination found enlarged cerebral ventricles, communicating lateral ventricles, bilateral cleft lip and palate. A 2500 gm male infant was delivered at 36 weeks' gestation, after which the diagnosis of septo optic dysplasia was made. PMID- 2222621 TI - Medication administration via the umbilical arterial catheter: a survey of standard practices and review of the literature. AB - A survey of 100 institutions was conducted regarding the use of medications through the umbilical artery catheter (UAC). Of the 63 institutions that responded, 40 allow medication administration through the UAC. Data were collected on which medications were believed to be safe and those believed not to be safe for administration through the UAC. Responders were also asked to comment on any problems related to particular medications, who administered the medications, the method of administration, and the preferred placement of the tip of the catheter. PMID- 2222624 TI - Doppler umbilical artery velocimetry in fetuses with polyhydramnios. AB - Polyhydramnios is a condition of multiple etiologies, many of a benign nature, but some of which are incompatible with life. To evaluate Doppler velocimetry results as a prognostic parameter in these fetuses, we reviewed all of our cases of polyhydramnios that underwent Doppler analysis in the third trimester. Fifty four fetuses were studied. Eleven (20.4%) had abnormal waveforms and 43 (79.6%) had normal waveforms. An abnormal waveform was associated with a significantly higher incidence of congenital anomalies, perinatal mortality and intrauterine growth retardation. Six of the 11 fetuses had abnormal karyotypes. Macrosomia was present in 37.2% of fetuses with normal waveforms and in no fetus with an abnormal waveform. Doppler analysis may aid in the counseling and management of patients with polyhydramnios. In cases with an abnormal ratio, the physician and patients should be prepared for a poor outcome and third trimester genetic analysis should be strongly considered. PMID- 2222625 TI - Effect of intrauterine growth retardation on renal function on day one of life. AB - We measured inulin clearance per kilogram, fractional sodium excretion per kilogram, osmolality, and urinary prostaglandin concentration in seven growth retarded neonates and six appropriately grown neonates matched for gestational age during the first 24 hours of life to determine the effect of fetal growth retardation on renal function. There was a nonsignificant reduction in inulin clearance per kilogram in the growth-retarded neonates (p = 0.11). Inulin clearance correlated with gestational age in both groups. It was significantly correlated with birthweight in the growth-retarded group (p less than 0.05) but did not reach significance in the control group (p less than 0.06). Fractional sodium excretion was significantly higher in the growth-retarded fetuses (p less than 0.05). This increase was not explainable by differences in mean blood pressure and intravenous fluid intake, although differences in urinary prostaglandin concentrations during the study interval may be involved. In conclusion, we have demonstrated that growth retardation is associated with impaired renal maturation, which during the first 24 hours of life is manifest as decreased glomerular filtration rate and increased sodium excretion. PMID- 2222626 TI - Cervical internal os cerclage: description of a new technique and comparison with Shirodkar operation. AB - Internal os cerclage for cervical incompetence was performed in 90 patients who had previous McDonald procedure failure (70 patients) or had unfavorable cervical anatomy (short or lacerated cervix) for primary McDonald type cerclage (20 patients). Two different techniques were used: the Shirodkar operation (n = 44) with Mersilene band, and a simpler new technique (n = 46). The new technique is characterized by anterior colpotomy for exposure of the internal os, and a 0.6 mm nylon suture encircling the cervix to be tied high in the posterior fornix. The pregnancy outcome for both groups was similar. Late abortions of 8.7 and 11% and premature deliveries of 13 and 18% occurred in the new technique and the Shirodkar groups, respectively. The removal of the suture was generally difficult in the Shirodkar group and in eight patients analgesia and sedation were required. In the new technique group, the removal was easier and in only one patient was sedation required (p less than 0.0001). Severe vaginal discharge was found in 52% of the Shirodkar patients and none in the other group. Apparently the monofilament nylon suture prevented this side effect. It seems that the new technique is simpler to perform, involves fewer side effects, the removal of the suture is easier, and it is as effective as the Shirodkar procedure. PMID- 2222627 TI - Spectrum and natural history of congenital hyperparathyroidism secondary to maternal hypocalcemia. AB - Fourteen cases of congenital hyperparathyroidism secondary to maternal hypocalcemia have been reported. We report two additional cases that highlight the wide spectrum of the disease. We extensively studied the parathyroid function of these infants to test the hypothesis that the biochemical hyperparathyroidism found in these infants would be transient in nature, since the presumed etiology (maternal and subsequent fetal hypocalcemia) should disappear soon after birth with establishment of enteral feedings. Infant 1 was born to a mother with idiopathic hypoparathyroidism with poor compliance to therapy and documented hypocalcemia in pregnancy. Severe congenital demineralization and intrauterine fractures with clinical and radiologic bowing of the long bones were obvious. Bone mineral content and bone mineral content/bone width ratio, measured by photon absorptiometry, were both markedly below normal. Infant 2 was born to a mother with postsurgical hypoparathyroidism with excellent compliance. The mother was normocalcemic. The infant was clinically and radiologically asymptomatic. The bone mineral content was just at the lower limit of normal, but bone mineral content/bone width ratio was below the normal limits. Biochemical features include elevation of cord serum parathyroid hormone (1-84, radioimmunoassay) in both cases, coexisting with serum calcium, phosphorus concentrations within normal limits. Serum parathyroid hormone fell to within normal ranges by 9 days of age in both infants. With no treatment, bone mineral content at 1 month of age was normal in both infants. PMID- 2222628 TI - Alpha-thalassemia: prenatal diagnosis and neonatal implications. AB - Homozygous alpha-thalassemia major, or Bart's hemoglobinopathy, is the most common etiology of nonimmune hydrops in those of Oriental descent. The prenatal diagnosis can now be made utilizing DNA hybridization technique from fetal cells obtained by either amniocentesis or chorionic villus sampling. A case is reviewed documenting the utilization of DNA studies in managing patients known or suspected to have a history of alpha-thalassemia major. PMID- 2222629 TI - Effects of T's and blues abuse on pregnancy outcome and infant health status. AB - T's and blues (pentazocine and tripelennamine) abuse during pregnancy has been reported to be associated with adverse maternal and fetal effects. In this study, conducted at Parkland Memorial Hospital in Dallas, Texas, pregnancy outcome and health status of infants born to 23 T's and blues abusers were compared to a group of 100 unexposed women and their infants. Infants born to T's and blues abusers had significantly reduced birthweight, length, head circumference, and an increased frequency of major congenital anomalies (3 of 23), including two congenital cardiac anomalies. However, one of these cardiac anomalies occurred in the offspring of a woman who also reported moderate to heavy daily alcohol use during pregnancy. The other cardiac anomaly occurred in association with in utero anoxia. We therefore surmise that a known teratogen (alcohol) and perinatal complications caused two of the major anomalies, and not the pentazocine tripelennamine combination per se. PMID- 2222630 TI - Effect of active management on latent phase labor. AB - The effect of active management on latent phase labor was assessed in 197 consecutive nulliparous women. Active management resulted in a significant shortening of the latent phase but had no effect on active phase labor. Patients undergoing induction of labor had latent phases that were almost identical to the accepted norm. The effect of active management may be due to early diagnosis of labor and early intervention in the form of artificial rupture of membranes and selective high-dose oxytocin infusion. PMID- 2222631 TI - Safety and efficacy of combined ritodrine and magnesium sulfate for preterm labor: a method for reduction of complications. AB - Ritodrine hydrochloride and magnesium sulfate used in combination for preterm labor tocolysis have been cited for yielding excessively high complication rates. A retrospective chart review was performed to assess the frequency of these complications and to determine whether tocolysis can be continued despite complications. Of 95 patients managed with dual tocolytics, 61 had side effects sufficiently serious to warrant cessation of tocolytic therapy for an overall complication rate of 64%. After evaluation for objective evidence of pathologic conditions, 41 (67%) patients were restarted on dual tocolytics without further complication. It was deemed inappropriate to restart tocolysis in 20 patients, resulting in a 21% rate of complications. This allowed a significant increase in the number of patients delivering after 36 weeks (19.5% versus 50%, p less than 0.02) and a decrease in neonatal intensive care unit days per infant (3 versus 15.5 days, p less than 0.02). This suggests that aggressive continued tocolysis with multiple agents can be safe and efficacious with appropriate evaluation. PMID- 2222632 TI - Isolated fetal ascites: prenatal diagnosis and management. AB - The perinatal outcomes of four patients with isolated fetal ascites were evaluated. The ascites disappeared prior to delivery in 50% of the cases and was resolved shortly after delivery in the remainder. Excellent neonatal outcomes were observed. Thus, isolated fetal ascites may represent a separate condition that significantly differs from the general category of nonimmune hydrops in both perinatal courses and prognoses. The prenatal diagnosis and management of this condition are discussed. PMID- 2222633 TI - Risk factors for preterm premature rupture of the fetal membranes. AB - Preterm premature rupture of the membranes (PPROM) is a significant cause of prematurity, accounting for approximately one third of preterm births in the United States. PPROM occurs in approximately 0.7-2% of all pregnancies nationally, and has a reported recurrence rate of 21%. The elucidation of potential risk factors for PPROM could contribute to a better understanding of its etiology. To study the contributions of 20 potential risk factors, we undertook a case-control study in our clinic population, which has a 5-6% incidence of PPROM. One hundred and thirty-three patients experiencing PPROM were matched for race, age, parity and gestational age with undelivered patients. Studies performed included ultrasonographic examinations, blood levels of ascorbic acid and zinc, microbiologic assays, patient questionnaires, and chart reviews. After stratification of both groups into subgroups based on matching criteria, summary tests of significance and Mantel-Haenszel tests of odds ratios were performed. On univariate analysis the following factors achieved significance at the p less than 0.05 level with 95% confidence intervals: 1) previous history of PPROM 2) smoking (dose related) 3) fundal location of the placenta in the present pregnancy. 4) a prior history of cerclage. After regression analysis, we concluded that smoking and history of previous PPROM were found to be risk factors for PPROM in our inner city black population. PMID- 2222634 TI - Relationship of maternal to neonatal colonization with coagulase-negative staphylococci. AB - Infections with coagulase-negative staphylococci (C-S) have become problems of major clinical importance among very low birthweight infants in neonatal intensive care units. Colonization with slime-producing strains of C-S may be a risk factor for these infants in the development of invasive infections. The present study evaluated the maternal genital tract as a possible source for neonatal colonization with C-S. Specific objectives were to determine the incidence of vaginal colonization with C-S in pregnant women with special reference to slime-producing strains and whether transmission of C-S occurs from mother to infant during the process of vaginal delivery. Antenatal vaginal cultures were done on 465 women at different gestations of pregnancy. Additionally, 101 women and their newborn infants were cultured after vaginal delivery. Fifty-one percent of women were colonized with C-S during pregnancy, and no significant differences in colonization rates by trimester were found. Slime-positive isolates from pregnant women increased significantly from the first to the third trimester (40 to 68%; chi-square, 11.21, p less than 0.005). However, the proportion of slime-positive strains among the 30 infants who were colonized with C-S at birth was 40% (12 of 30). Although 30 infants were colonized with C-S at birth, only three were shown to have acquired the organism by maternal transmission determined by similarity of species, biotype, antibiotic sensitivity pattern, slime production, phage type, and plasmid pattern profile. Therefore 27 infants (26% of the total) most likely acquired C-S from environmental sources, including nursery attendants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222635 TI - First trimester growth delay in Trisomy 18. PMID- 2222636 TI - Breastfeeding: can it compete in the marketplace? PMID- 2222637 TI - A standardized interview that differentiates pregnancy and postpartum symptoms from perinatal clinical depression. AB - In a prospective longitudinal study, 202 primigravidas were assessed for depression using the National Institute of Mental Health's (NIMH) standardized clinical interview, the Schedule for Affective Disorders and Schizophrenia (SADS), and Research Diagnostic Criteria (RDC) at four periods: 10 to 14 weeks of pregnancy, 30 to 32 weeks of pregnancy, 1 to 2 weeks postpartum, and 14 weeks postpartum. Women's responses did not fit the SADS standardized questions and prescribed ratings because pregnancy and postpartum symptoms often mimicked depression symptoms. This was addressed by adding questions and scoring criteria to separate out pregnancy and postpartum symptoms from depression symptoms. Results showed that, after accounting for pregnancy-postpartum symptoms, women consistently claimed eight symptoms with high frequency and higher mean ratings: dysphoric mood, worrying, somatic and psychic anxiety, insomnia, fatigue, anger, and irritability. The findings suggest that 1) depression in pregnant and newly delivered women may be underdiagnosed if caregivers attribute their complaints or symptoms to time-limited somatic conditions; 2) depression may be overdiagnosed if clinicians use self-report measures solely, or without carefully interviewing women to separate the symptoms of depression from symptoms of pregnancy and postpartum; and 3) women's reactions to perinatal symptoms may have some bearing on the development of depression then or later. Simple clinical and social amelioration of the symptoms of distress might reduce their effect and diminish the rate of mistaken diagnoses of depression. PMID- 2222638 TI - Postpartum depressive disorders: changing trends. AB - For centuries, there has been speculation regarding the etiology of postpartum depression. An improved diagnostic classification has emerged, however, as the universality of the syndrome has been recognized and the role of hormonal, genetic, and obstetric variables considered. In addition, different cultures have different perceptions of the needs of the new mother. The emphasis in investigative work now appears to be in the psychosocial and psychodynamic areas. Our recent research focused on identification of risk factors early in pregnancy, including a history of depression, separation from one or both parents in childhood or adolescence, poor parental emotional support in childhood and adulthood, poor relationship with husband or partner, economic problems, and dissatisfaction with amount of education. We suggest that physicians, nurses, and mental health professionals be aware of the emotional status of their patients, familiarize themselves with the risk factors, and initiate a program of careful postpartum follow-up. These measures will help to improve recognition and management of the woman at risk for postpartum depression. PMID- 2222639 TI - Midwifery in Ontario: a survey of interest in services. AB - Maternity care for women in Ontario is provided almost exclusively by physicians, the majority of whom are obstetricians. Using a self-administered questionnaire, pregnant women in one Ontario city were surveyed about their interest in midwifery care as an alternative to physician care. Although 3 percent of the women surveyed had used a midwife, 60 percent expressed an interest in midwifery care, particularly the counseling and support aspects. Over 11 percent showed an interest in complete primary midwifery care. PMID- 2222640 TI - Vaginal birth after two or more cesarean sections: a five-year experience. AB - Allowing a trial of labor in patients who have had a single low transverse cesarean section has become increasingly accepted and widespread in the United States. Evidence with regard to the safety of this practice in patients with two or more prior cesarean births has, however, been sparse. We performed a retrospective review of the charts of 170 patients who had undergone two or more low transverse cesarean deliveries and subsequently delivered at Wishard Memorial Hospital between January 1, 1983, and December 31, 1987. Of 35 of these women who underwent a trial of labor, 27 (77%) had a successful vaginal delivery. No increase in maternal or fetal morbidity or mortality was associated with labor. The women who underwent trial of labor had fewer postpartum complications and shorter hospital stays. Although the number of patients in this study was small, growing evidence appears to support a trial of labor in patients with two or more prior cesarean sections as a safe and successful alternative to elective repeat cesarean section. PMID- 2222641 TI - Treatment refusal, noncompliance, and substance abuse in pregnancy: legal and ethical issues. AB - Prenatal caregivers often note that the behavior of pregnant patients creates the risk of fetal harm. Three such cases are reviewed, together with care providers' responses and relevant law. Pregnant womens' rights to disregard medical advice are increasingly being overridden in courtrooms and bedside hearings. To preserve the patient-provider relationship, and to avoid coercive actions that may have little legal basis, emphasis should be on helping the woman act in her own best interest and that of her fetus, rather than on the law or the courts as a means of directly or indirectly controlling her behavior. PMID- 2222642 TI - Effects of epidural analgesia: some questions and answers. AB - The effects of epidural analgesia on first labors have been studied by Thorp and colleagues. One study has been published and is the subject of a question-and answer discussion, presented here. In this study 711 consecutive nulliparous women at term, with spontaneous onset of labor and cephalic presentation, were divided into one group (n = 447) who received epidural analgesia in labor and another group (n = 264) who received narcotics or no analgesia. The frequency of cesarean section for dystocia was significantly greater (p less than 0.005) in the epidural group (10.3%) than in the nonepidural group (3.8%), even after selection bias was corrected and the variables of maternal age and race; gestational age; cervical dilatation on admission; use, duration, and maximum infusion rate of oxytocin; labor duration; presence of meconium; and birth weight were controlled. For both groups the frequency of cesarean section for fetal distress was similar (p less than 0.20), and the frequency of low Apgar scores at 5 minutes and cord blood gas values showed no significant differences. The authors concluded that "epidural analgesia in labor may increase the incidence of cesarean section for dystocia in nulliparous women". PMID- 2222643 TI - Lactation outcome. PMID- 2222645 TI - [Resistance and retention as critical factors in silver amalgam restoration of endodontic posterior teeth. A clinical focus]. AB - The root canal therapy does not make sense if it is not going to be restored properly. Even though we must keep in mind all the steps necessary to build up any vital tooth, we should emphasize the retention and resistency due to the fragility of endodontically treated teeth and to the destruction of these teeth. Even though the use o silver amalgam has been often questioned, we still consider amalgam as a proper material of a good half worm life to build up endodontically treated posterior teeth. Resistency and retention were considered as the essential factors to achieve the integrity of final restorations. We have analyzed the remaining tooth structure, periodontal support, biomechanics properties of the most used restorative materials and the variations of the forces. The different opinions on the concepts and technics have been reviewed and the final practical conclusions discussed. PMID- 2222644 TI - [Fissure sealants: clinical study]. AB - A total of 132 sealants are applied to 55 children, over a period of one to five years. The results show a Complete Retention of 76.5%, a Partial Loss of 12.8% and Complete Loss of 10.6%. PMID- 2222646 TI - [Fluoroprophylaxis by the parenteral route]. AB - The author sustains the value parenteral fluoroprophylaxis; this method of administering fluoride is the most appropriate during the period of formation of the enamel and in the pre-eruptive stage of the tooth, and is thus an essential procedure in a fluoroprophylaxis programme, which should be used above all in the case of public health measures. PMID- 2222648 TI - [Metastatic hypernephroma in oral soft tissue]. AB - Oral metastatic tumors are rare. A case of primary affection of oral soft tissues by metastatic hypernefroma, without radiologic evidence of bone involvement, is presented in this paper. Review of the literature reveals that the gingiva is the commonest location of metastatic hypernephroma in the oral soft tissues. The most important clinicopathology and therapeutic features are also reviewed. PMID- 2222647 TI - [Caries prevalence of a school population]. AB - We have made a cross-sectional study about dental caries in 883 children between 6 and 15 years old, belonging to 3 public schools representing the municipal district of Tetuan (Madrid). The studied variables, that were related with presence/absence of caries were: age, sex, school, social class, number of meals per day, tooth brushing and use of fluor. We have also established the indexes DMFT, dmft, DMFM, together with the affection percentage of each tooth and its graphic representation. PMID- 2222649 TI - [Periodontal treatment needs in a Spanish school population]. AB - The aim of this study was to assess the periodontal treatment needs of the population under 20 years of age in Spain. 1469 young people, aged 7, 12 and 15 19 years, and representing the urban (60%) and rural (40%) population from Spain were evaluated using the Community Periodontal Index of Treatment Needs (C.P.I.T.N.). In the first age group (7 years), 12% presented calculus or overhanging restorations, and 45% had bleeding upon probing only. In the age group of 12 years the proportion of individuals with calculus, overthanging restorations or moderate pocket depths was 39%, while 38% had gingivitis as their highest treatment need. In the oldest group (15-19 years) the number of subjects with bleeding upon probing decreased to 17%, while the percentage of individuals having moderate pockets, calculus or overhanging restorations increased to 67%. 1% of this youngsters had pockets of 6 mm. or over. At age 7, only 30% had "acceptable gingival health", and no more than 15% of the 18 year-olds reached this condition. PMID- 2222650 TI - [Periodontal treatment needs in a Spanish school population. 2. Intraoral distribution of different signs]. AB - The aim of this study was to assess the prevalence of the different periodontal disease indicators used in the C.P.I.T.N. per sextant in the Spaniard population under 20 years of age. We have examined a randomly chosen sample of 1450 school aged individuals, 7, 12 and 15 to 19 years old. We have observed a healthy periodontium more frequently in the upper anterior region, calculus predominates in the lower incisors close followed by molars, and periodontal pockets of 4 mm or deeper were commonly found in the molar regions. We could'nt detect important deviations from this distribution pattern in the different age groups or between males and females. PMID- 2222651 TI - [Prevalence of caries in Spanish school children and youth of 7, 12 and 15 to 19 years of age]. AB - The aim of this study was to assess the dental caries prevalence and severity of the population under 20 years of age in Spain. 1469 young people, aged 7, 12 and 15-19 years, and representing the urban (60%) and rural (40%) population from Spain were evaluated, registering the decayed, extracted or filled teeth for primary and permanent dentition. Average D.M.F.T. for 7, 12 and 15-19-years-old were 1.5, 3.5 and 6.6 respectively. A comparison of the results with those of previous studies showed that the average D.M.F.T. scores have decreased since 1984. We have also observed an increment in the number of caries-free children reaching the 57.9% in the age group of 7 years. But this excitement over the increase in the number of caries-free children must be tempered by the recognition that 35% of these individuals had 70% of the caries. We still need educational, preventive and restorative programs, and focus our efforts in detecting and treating the highly susceptible children. PMID- 2222652 TI - [Validity of partial systems of periodontal examination in epidemiological studies]. AB - The purpose of the present study was to determine the representativeness of partial examination in the assessment of the average severity and the prevalence of periodontal disease. 343 subjects aged 7, 12 and 15-19 years were examined for the presence or absence of gingival bleeding after gentle probing, supra or subgingival calculus and pocket depths of 4-5 mm., or 6 mm. and over, of each tooth. Three sets of average severity and prevalence scores were prepared: based on the full mouth examination, on observations made from the index teeth of the P.D.I., and on the six teeth utilized for the C.P.I.T.N. in this age group. Partial indices tended to underestimate the real prevalence of the different signs, and slightly overestimate severity, being these observations statistically significant. Average severity scores were obtained more accurately with the six Ramfjord teeth, while real prevalence rates were better determined with the C.P.I.T.N. teeth. From an epidemiological point of view, the real significance of the differences observed should be further determined. PMID- 2222653 TI - [Caries prevalence and periodontal treatment needs in the same individuals]. AB - The aim of this study was to determine whether dental caries and periodontal disease occur frequently in the same subjects 1469 young people, aged 7, 12 and 15-19 years, and representing the urban (60%) and rural (40%) population from Spain were evaluated. Dental caries and periodontal treatment needs were registered according to the index D.M.F.T. and C.P.I.T.N., following the criteria of WHO. We have found a highly significant relation between both variables, average D.M.F.T. scores increased as periodontal treatment needs were more advanced. Those subjects with lower codes of C.P.I.T.N. presented also lower D.M.F.T. scores, while these individuals with higher D.M.F.T. scores, based on a great number of open carious lesions, were more affected for periodontal disease. It does not support either a directly synergistic or antagonistic correlation in the prevalence of these two diseases in the same subjects. Dental health status is at a certain time an end result of years of varying dental health behaviour. In industrialized countries a variety of factors seems to determine the prevalence of dental caries and/or periodontal disease: dietary habits, access to fluorides, efficacy of oral hygiene measures, utilization of dental health care services. These data and ideas supported the strategy of preventing the dental caries and periodontal disease simultaneously. PMID- 2222654 TI - [Relationship of dental treatment and oral hygiene to caries prevalence and need for periodontal treatment]. AB - The aim of this study was to examine the relationship between differences in dental attendance and oral hygiene patterns and dental caries and periodontal treatment needs. 1469 young people, aged 7, 12 and 15-19 years, and representing the urban (60%) and rural (40%) population from Spain were evaluated. Dental caries and periodontal treatment needs were registered according to the index D.M.F.T. and C.P.I.T.N., following the criteria of W.H.O. Regular dental attendance was observed in 16.6% of subjects examined, and only 9.4 saw a dentist regularly for dental prophylaxis. Statistical analyses showed that while the more frequent the dental visits, the lower the rate of caries, and periodontal treatment needs, the higher, however, the average number of fillings and the D.M.F.T. scores. These individuals had the higher number of functioning teeth, restored or sound, but they also had the disadvantage of having higher levels of disease experience. By the other way the individuals who saw the dentist regularly for dental prophylaxis presented the lower caries rate and periodontal treatment needs, the fewer tooth loss, and also an important reduction in the D.M.F.T. scores. Similar observations had been made in the individuals who brush their teeth frequently or with a correct technique. The results suggested that while frequent dental visits do not apparently help to prevent the onset of further dental disease, we can achieve this goal with regular preventive oriented dental therapy. PMID- 2222655 TI - [Presence of caries and periodontal disease in Spanish students. Overview of results obtained in different localities]. AB - Results of our survey in 11 locations of Spain are assembled in an overview showing percentages of persons according to the highest C.P.I.T.N. code defected for each one, the prevalence of caries-free-children and mean D.M.F.T. scores. We have also studied the differences between urban and rural populations. Rural children presented higher D.M.F.T. an D.T. scores. PMID- 2222656 TI - [Interviews with HIV seropositive subjects identified at the time of blood donation: consequences for pre-donation interviews]. AB - This study is based upon an interview with 31 individuals recently detected human immunodeficiency virus (HIV) seropositive through the systematic screening of blood donations. The location of the blood donation, the type of blood donor, the risk of HIV infection, were established. Questions dealt with the use of blood donation as a diagnosis test and on the notion of an oral or written self exclusion before the blood donation. The majority of the individuals had a classical risk factor of HIV infection and had given blood for serological testing. This data can allow an adaptation of the medical interview preceding the blood donation to the present epidemiological context of HIV infection. PMID- 2222658 TI - [The "polymerase chain reaction" (PCR) in seronegative subjects at high risk for HIV infection (Report of a congress at San Francisco, June, 1990)]. PMID- 2222657 TI - [The medical interview motivated by the discovery of markers of viral hepatitis permits the identification, in blood donors, of behavior at risk for HIV infection]. AB - From December 1988 to September 1989, 973 blood donors, deferred for anti-HBc reactivity, Ag-HBs positivity, elevated ALT, isolated or associated, but negative for anti-HIV, were interviewed in our blood center in the weeks after donation. Among these 973 donors, 53 (5.4%, 46 males, 7 females) were found at risk for HIV infection: intravenous drug abuse: 24 cases; heterosexuality with multiple partners: 17 cases; homosexuality: 8 cases; sexual relations with persons at risk: 4 cases. These 53 donors did not recognize their risk behaviour during the medical talk before donation. 25 out of these 53 donors were seen afterwards and one of them, homosexual man, seroconverted for anti-HIV seven months after the anti HIV negative but anti-HBc positive blood donation. We conclude that, in our experience, director surrogate viral hepatitis markers help to identify donors at risk for HIV infection, and, in one case, earlier in the course of demonstrated HIV infection than the enzyme immunoassays currently licensed. PMID- 2222659 TI - [Attitudes, knowledge and behavior of 3 groups of Spanish dentists on methods of caries prevention]. PMID- 2222660 TI - [Occlusal examination in the diagnosis and treatment of periodontal disease. 2. Examination of signs and symptoms in dental structures. Periodontal, radiographic and clinical evaluation of occlusion]. PMID- 2222661 TI - [Erosive lichen planus with oral and plantar involvement]. AB - We present herein a case of an unusual variant of lichen planus characterized by chronic and painful ulcerations of the feet, erosive oral lesions and nail alterations. We emphasized the importance of the oral lesions in the correct diagnostic of these patients. PMID- 2222662 TI - [Eosinophilic granuloma of the jaws. Presentation of 2 cases]. PMID- 2222663 TI - [Bacteriocins of Streptococcus mutans: mutacins]. AB - A bioliographic survey about the production of a certain bactericidal substance (mutacins) by Streptococcus mutans has been done. The importance of bacteriocins of this micro-organism is due to its utility as a possible anti-caries agent performing as an influential factor in the colonization of the oral cavity, and also for serving for the typing of bacteria as an epidemiological "finger printing", determining the way of transmission of this micro-organism. Besides of stressing its clinical and epidemiological utility, we develop a review of other microbiological aspects. PMID- 2222664 TI - [Dynamic orthodontics]. PMID- 2222665 TI - [Fixed partial denture on implants. Prosthodontic and biomechanical considerations]. AB - In this issue are analyzed the factors that support the selection of the partial edentulous patients, for the construction of partial fixed prosthesis implantosupported, and the biomechanical considerations that we have to consider in relation to: relation implant-bone, the use of natural teeth, part of the jaw, length of the space, opponent jaw and materials. PMID- 2222666 TI - [Retention using grooves in silver amalgam cavities]. PMID- 2222667 TI - [Boxes and pits as retention systems in silver amalgam fillings]. PMID- 2222668 TI - [Practical application in oral health of a health education program for students]. AB - Oral health has been studied in a group of 680 students. E.F.H. program has been integred in the contents of the General teaching. PMID- 2222669 TI - [New aspects of the physiology of dental occlusion. 1. Morphology of the temporomandibular joint]. AB - The present article review, in the recent literature, some anatomical and biomechanical concepts about the temporomandibular joint in order to the better understanding of the physiology and dysfunction of the articulation. We point out the references about the function of the meniscus in the mandibular dynamics and the functional matrix concept and its relationship to temporomandibular joint dysfunction. PMID- 2222670 TI - [Dendritic cells in chronic adult periodontal disease]. AB - At the gingiva there are two cellular populations with mediation capacity in the immunoregulation, whose mechanisms seen to be implicated in the pathogenesis of the periodontal disease. One of these populations is formed by the macrophages and the other one by the Langerhans cells belonging to the epithelia. In this paper wr are demonstrating that both populations keep an inverse proportional relation in the two sides of gingival epithelium. In the oral side, the Langerhans cells are predomiating, while in the periodontal pocket they are in small number, in comparison with the macrophages, which are highly abundant and forming a subepithelial band. PMID- 2222671 TI - [Dens invaginatus]. AB - Dens invaginatus is an abnormal enamel growth first described by Salter in 1855. It has an incidence between 0.4 - 10%, and the tooth most frequently affected is the lateral upper incisor. Its etiology is not explained. There are many asymtomatic cases and others with symptoms derived from periapical lesions. Treatment must be as conservative as possible. A bibliographic review has been made and we demonstrate a radiologic sequence of the many cases observed in our Service in the last two years. PMID- 2222672 TI - [Transverse fracture of the mandibular body. Analysis of a case]. PMID- 2222673 TI - [Class III. Current criteria for diagnosis and treatment 1]. PMID- 2222674 TI - [Pins as a retention system in silver amalgam fillings]. PMID- 2222675 TI - [Current review of local anesthetics and their use in dental practice]. PMID- 2222676 TI - [New aspects of the philosophy of dental occlusion. 2. Biomechanics of the temporomandibular joint]. PMID- 2222677 TI - [Periodontal receptors. Review]. PMID- 2222678 TI - [Anxiety before dental treatment. Its quantification]. PMID- 2222680 TI - What is your diagnosis? Urticaria pigmentosa. PMID- 2222679 TI - [Twins in medicine and dentistry. Review]. PMID- 2222681 TI - Rett syndrome. The Puerto Rican experience. AB - We have diagnosed and followed four Puerto Rican females with Rett Syndrome (RS). Their ages, when first examined, ranged from 10 months to 11 years. The classical symptoms of decreasing head size, onset of hand wringing movements with deterioration of milestones as well as EEG abnormalities were present in all. Case No. 1, considered our index case was evaluated by us and lost to follow-up for many years while residing in the mainland U.S.A. where multiple evaluations failed to give a definite diagnosis. Upon her return to Puerto Rico she was diagnosed by us in retrospect as having RS. These are the first Puerto Rican girls reported with RS and in doing so we hope for a better understanding of the syndrome by our medical community. Because of the devastating effects of RS, early diagnosis and parental counseling will be beneficial for patients and their families. PMID- 2222682 TI - [The future of public health in Puerto Rico]. PMID- 2222683 TI - Fulminant Wilson's disease: a report. AB - A 21 y/o female presented with fulminant hepatic failure and hemolysis. On the basis of the clinical presentation, levels of ceruloplasmin and serum copper a presumptive diagnosis of Wilson's disease was made. In spite of supportive measures and hemodialysis, the patient died one week after admission. Postmortem examination showed cirrhosis and increased copper stores in the liver, corroborating the clinical diagnosis of Wilson's disease. Study of the four siblings revealed that two are carriers, one is healthy and one may have the disease. Wilson's disease is a rare cause of fulminant hepatic failure that must be suspected specially when hemolysis is associated to the clinical picture. This mode of presentation is virtually fatal and early liver transplantation is the best form of therapy. PMID- 2222684 TI - Phaeohyphomycosis--first case in Puerto Rico. AB - A 24 year-old woman with systemic lupus erythematosus developed a subcutaneous nodule on the back which upon histopathological examination was found to be a case of phaeohyphomycosis. To our knowledge, this is the first case of the condition to be reported in Puerto Rico. PMID- 2222686 TI - The role of diet in modulating brain metabolism and behavior. PMID- 2222685 TI - [Aspirin in the prevention and management of coronary artery disease]. PMID- 2222687 TI - [Meniere's disease. An analysis of clinical findings]. AB - During a period of about 25 years 500 patients with Meniere's disease underwent treatment for their disease in the ENT clinic of the Charite Hospital in Berlin. In a long-term follow-up study of the course of the disease, 170 patients (80 female, 90 male) with a minimum duration of illness of 5 years could be registered. The detailed analysis based on differentiation of vertigo attacks, audiological and vestibular findings offered 3 different phases of the natural course of Meniere's disease: 1. Early phase: Vertigo attacks and fluctuating hearing loss mainly in the low-tone frequencies; 2. Chronic phase: Decrease of frequency and duration of attacks; 3. Late chronic phase: Hearing loss of nearly 50-60 dB and loss of vestibular excitability (caloric response, side difference ca. 50%). In consideration of neurological symptoms in the late chronic phase symptoms of Meniere's disease are changing into symptoms of vertebrobasilar insufficiency. The natural course of Meniere's disease and resulting therapeutical and diagnostical aspects require long-term therapeutic planning. An appropriate schedule is suggested. PMID- 2222688 TI - [Temporary threshold shift after nuclear magnetic resonance tomography]. AB - The third-octave band levels of the noises produced in a MR-imager (1.0 Tesla Magneton, Siemens) were measured. Corresponding sounds presented through earphones have been used in simulation experiments to produce in normal-hearing listeners a temporary threshold shift lasting several minutes. These effects could be verified objectively using otoacoustic emissions. The consequences especially for patients with already impaired hearing are discussed: ear protection is strongly recommended. PMID- 2222689 TI - [Improved inner ear diagnosis by controlled use of computerized tomography]. AB - Problems in the examination of the inner ear using conventional CT are described. Intraoperative findings often differ from CT findings. A new development HR-CT is introduced. Findings of middle and inner ear malformations and otosclerosis are demonstrated. It is shown that HR-CT imaging using a new 1024 matrix, enables better spatial resolution. This new CT technique improves inner ear examination, especially in the preparation for cochlear implantation. PMID- 2222690 TI - [Accuracy of measurement and comparability of anterior rhinomanometry and whole body plethysmography in determination of nasal resistance. Studies with a mechanical model]. AB - The degree of accuracy of anterior rhinomanometry and the plethysmographic method in determining nasal resistance was examined in a mechanical model. The plethysmographic method allows a precise estimation of nasal resistance. It was found that the absolute variation of the plethysmographically measured values is not greater than 5%. Anterior rhinomanometry as described by Bachmann (2) allows a valid estimation of the pressure-flow relation. Here, too, inaccuracy remains within a range of 5% if the values are recorded with an X-Y-plotter. With the system developed by EVG, a microprocessor-controlled analysis is also possible. The flow rate is measured at pressure rates of 75, 150, and 300 Pa. Inconstancies in respiratory flow cause deviations from the correct pressure-flow graph. Should these deviations accidentally coincide with the predefined points of evaluation these erroneously achieved results will be assumed to be representative for the whole graph. This analytical fault has meanwhile been corrected by interpolating the points at the predefined pressure rates. Due to the differences in analytic techniques the methods of determining nasal resistance are not comparable in practice. The authors therefore recommend that, in addition to the usual results of analysis, average value of nasal resistance be determined for each measuring procedure. Today, this can be done without any problem by using microprocessors. PMID- 2222691 TI - [Olfactory neuroblastoma--tumor entity or complex clinical picture?]. AB - Clinical and radiological findings in seven cases of olfactory neuroblastoma are reviewed and discussed in the light of the international literature. The report provides further evidence of difficulties related to the predictability of the condition's clinical course, diagnosis, and therapeutic consequences. Moreover, the lack of uniform CCT and NMR features indicates that the discussion about the genesis, the biological action, the terminology, and therapy of these tumors has not yet reached a conclusion. PMID- 2222692 TI - [Principles of therapy with fission neutrons and boron neutron capture therapy for radioresistant head-neck malignancies]. AB - Neutron therapy has proven to be clinically useful in cases of advanced, slow growing radioresistant head and neck carcinoma. Therapeutic effects might be based on direct DNA damaging and thus immediate cell-killing, on the generation of free oxygen radicals and, among others, on the fact that heavy particle radiation is said to be less dependent on the presence of oxygen than gamma rays, i.e. on a lower oxygen enhancement ratio (OER). The smaller difference in reaction between oxygenated and nonoxygenated cells could entail advantages as well as disadvantages, depending on the characteristics of the tumor cell population and of the normal tissue. It is therefore essential to select patients and tumours with an expectedly high therapeutic gain factor. Fission neutrons for tumour therapy: As evaluated by several in vitro and in vivo studies (11/13) the biological efficiency (RBE) of the RENT (Reactor Neutron Therapy) beam in Munich seems to be among the highest of all clinically used neutron beams. For a single dose range between 2 and 8 Gy the RBE for chronic radiation damage is relatively small (2). Consequently, patients with recurrent or metastatic carcinomas of the head and neck are treated with a single dose of 200-250 cGy after previous surgery and/or combined radiochemotherapy. The main limitation of fission neutrons is the small penetration depth. Possibilities of clinical implementation of boron neutron capture therapy (BNCT) in otorhinolaryngology: In near surface tumours it is possible to administer high doses of 10boron not selectively, i.e. no selective tumour-seeking compound is needed. Animal experiments with intratumoural injection of 10boron glycine have shown a strong effect on tumour growth delay (18).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222693 TI - [Experimental studies for photodynamic therapy of malignant tumors of the mouth cavity, larynx and pharynx with the photosensitizer methylene blue]. AB - Squamous-cell carcinomas of the upper aerodigestive tract can be destroyed in vitro through photosensitization with Methylene blue and subsequent radiation with red laser light. It is impossible to obtain the same results with sensitization or light radiation alone. The paper discusses the conditions under which this procedure might develop into a truly selective photodynamic therapy method. PMID- 2222694 TI - [The larynx--another organ manifesting Crohn disease]. AB - A very rare case of Crohn's disease of the larynx in a 66-year-old male is reported. During the rapid development of Crohn's disease there was an involvement of the right vocal cord and the right arytenoid. PMID- 2222695 TI - [A short history of hearing research. I. Antiquity]. AB - This review describes important steps in the history of basic research on the function of the hearing organ. The present, first part revisits the period between Empedocles and Galen, focussing on the ideas of Empedocles and Aristotle. It is unlikely that they knew the cochlea. Based upon a more general theory of interaction, however, Empedocles in the fifth century B.C. compared the hearing organ with a bell and claimed that it is capable of not only receiving, but also generating sound. Using Empedocles's theories of sound and the four elements, Aristotle proposed that sound is sensed by an air-filled resonant cavity in the head located behind the eardrum. The postulated cavity may have been identified with, or at least included, the middle ear. Aristotle's ideas dominated the theory of hearing for two millenniums. PMID- 2222696 TI - [Personal experiences. Photography of the tympanic membrane]. PMID- 2222697 TI - The epidemiology and prevention of child pedestrian injury. AB - Of pedestrian injuries that occur every year, approximately 50,000, including 1300 fatalities, are experienced by children between the ages of 1 and 14 years. Despite the importance of the problem, the pedestrian safety issue is often neglected in reports on vehicular injuries. Children between the ages of five and nine years, boys, and children in lower socioeconomic class are at higher risk of pedestrian injury than other children. Childhood pedestrian injuries take place predominantly in residential locations close to home and frequently occur while the child is at play. The risk of pedestrian injury to children is higher than that of other age groups when adjusted for traffic exposure, and a variety of developmental limitations may account for this fact. In spite of these limitations, children undertake collision avoidance maneuvers far more often than drivers do. Accident analyses have identified 15 different accident types, each reflecting a unique combination of human and environmental factors. Among children, the most frequently observed accident type is the midblock dart-out. Programs to modify pedestrian behavior, driver behavior, and vehicle design have met with modest success. In the United States, the cultural and political environments have not been favorable to the injury prevention effort. Urban designers and traffic engineers in Europe have undertaken a variety of modifications of the physical environment, and some of these have been successful in preventing pedestrian injuries to children. PMID- 2222699 TI - Youth and traffic safety: the effects of driving age, experience, and education. AB - This paper examines the effect of driving age, driving experience, and mandatory driver's education on traffic fatalities of youth. Data are examined for 47 states, nine years and for ages 15-17. It is found that the age of drivers is an important determinant of fatalities, and that the propensity toward fatalities is greater at younger ages. This age effect is not offset to any major degree by the lack of experience of new drivers at later ages. PMID- 2222700 TI - Safety effects of relaxing California's clean-record requirement for driver license renewal by mail. AB - A pilot program was established in California in 1982 authorizing mail renewal of driver licenses for persons under age 70 lacking clean (accident- and conviction free) 4-year driving records, but showing clean 2-year records at selection. Such drivers constitute about 14% of California's renewal population, or about 500,000 renewees per year. Eligible drivers whose licenses expired in 1983 were subjects of the present study. Half of them were randomly assigned to a group whose members were sent offers of renewal by mail and the other half were sent standard renewal notices requiring appearance in a field office and successful completion of vision and traffic law tests. Traffic accidents and convictions following the mailout of these documents were tracked for both groups; results presented here cover a 4-year period subsequent to mailout. During this period (a normal license term in California), no significant overall difference was shown between the groups with respect to subsequent convictions or accidents. However, significant detrimental effects on accidents were noted for a subgroup of drivers who had experienced recent traffic violations or accidents which were not on their records at selection. Implications of these results are discussed. PMID- 2222698 TI - Evaluation of the penetration test for bicyclists' helmets: comparative performance of hard shell and foam helmets. AB - A project was undertaken to evaluate the utility of the penetration test in the Australian Standard devoted to the testing of lightweight helmets for bicycle riders. The project revealed aspects of the protective performance of conventional hard shell helmets and recently developed helmets manufactured entirely from expanded polystyrene foam. Hard shell helmets were found to provide good performance in a range of loading conditions applied to them during testing. In contrast, foam helmets provided very poor resistance to concentrated loads produced during impacts with small, sharp objects but they had greater capacity than hard helmets to withstand distributed loads produced during impacts with flatter objects. The presence of the penetration test in the Australian Standard was determined to have produced the good all round performance of hard helmets which met its requirements. Two tests were proposed as alternatives to the penetration test. They would evaluate foam and hard helmets on equal terms at the cost of abandoning the requirement of helmets to withstand concentrated loads. PMID- 2222701 TI - Limitations of data compiled from police reports on pediatric pedestrian and bicycle motor vehicle events. AB - Police reports were compared to the information provided by a hospital monitoring system for children under 15 years old injured as pedestrians and bicyclists by moving motor vehicles in Orange County, California. The analysis was limited to identifying caveats in the police report database. Underreporting by police was conservatively estimated at 20% for pedestrians and 10% for bicyclists. Comparison of the pedestrian databases suggested underreporting by police of incidents involving 0-4-year-olds, nontraffic incidents, incidents in which the vehicle was backing up, and cases not involving a child crossing a street. Comparison of the bicyclist databases indicated an underreporting by police of nontraffic cases. These caveats, in part, are related to police agency reporting requirements. The police injury severity scale was found to correlate poorly with a scale based on medical diagnoses, and substantial underreporting by police of serious injuries was demonstrated. We suggest that utilization of police injury severity scales be limited to categories of fatal, injured, and not injured (when available). PMID- 2222703 TI - City curfew ordinances and teenage motor vehicle injury. AB - Several U.S. cities have curfew ordinances that limit the late night activities of minor teenagers in public places including highways. Detroit, Cleveland, and Columbus, which have curfew ordinances, were compared to Cincinnati, which does not have such an ordinance. The curfew ordinances were associated with a 23% reduction in motor vehicle related injury for 13- to 17-year-olds as passengers, drivers, pedestrians, or bicyclists during the curfew hours. It was concluded that city curfew ordinances, like the statewide driving curfews studied in other states, can reduce motor vehicle injury to teenagers during the particularly hazardous late night hours. PMID- 2222702 TI - The real number of road traffic accident casualties in The Netherlands: a year long survey. AB - Between August 1986 and July 1987 more than 24,000 households, containing nearly 67,000 persons, were surveyed by telephone about traffic injuries during the past three months. Expressed on an annual basis, approximately 430,000 people, or about 1 in 34 of the Dutch population, had suffered some sort of injury in a road accident. The road traffic morbidity was, therefore, 2,942 per 100,000 inhabitants. Of these, about 135,000 had to be treated in hospital (20,000 as inpatients). More than 100,000 did not need treatment. Cyclists formed by far the largest category of road user, but mopedists had the highest injury rate per kilometer travelled. 210,000 of these casualties fell within the definition for recording by the police. The police recorded only 49,748 traffic casualties, or about 25%, during the same period. The police data were not representative; the completeness declined according to severity of the injuries: inpatients, about 70%; outpatients 26%; extramural about 11%. Cyclists (11%), children (9%), and single vehicle accidents (5%) were very much underrepresented. The largest category of road user is cyclists, not car occupants as indicated by the police data. A number of recommendations are made for supplementing the police data and the existing hospital inpatient data. These include extending the Home Accident Recording System of outpatients and the General Practitioner Panel to include road accident victims. Together a representative sample of 95% of all those receiving medical treatment would thus be obtained. PMID- 2222704 TI - Traffic accidents in Kuwait: an economic dimension. AB - The cost per traffic fatality in Kuwait is assessed, comparing three different studies, and is found to be in excess of US $500,000. The three studies employ somewhat different methods. PMID- 2222705 TI - Formulating accident occurrence as a survival process. AB - A conceptual framework for accident occurrence is developed based on the principle of the driver as an information processor. The framework underlies the development of a modeling approach that is consistent with the definition of exposure to risk as a repeated trial. Survival theory is proposed as a statistical technique that is consistent with the conceptual structure and allows the exploration of a wide range of factors that contribute to highway operating risk. This survival model of accident occurrence is developed at a disaggregate level, allowing safety researchers to broaden the scope of studies which may be limited by the use of traditional aggregate approaches. An application of the approach to motor carrier safety is discussed as are potential applications to a variety of transportation industries. Lastly, a typology of highway safety research methodologies is developed to compare the properties of four safety methodologies: laboratory experiments, on-the-road studies, multidisciplinary accident investigations, and correlational studies. The survival theory formulation has a mathematical structure that is compatible with each safety methodology, so it may facilitate the integration of findings across methodologies. PMID- 2222706 TI - Evaluating marine traffic safety at channels. AB - An approach for measuring effects of policy schemes for improving marine traffic safety at channels is presented. Operational models involving traffic, channel, and ship characteristics are provided, and both collision and channel deviation risks of actual channels are quantified using them. Moreover, traffic control, speed regulation, and center line indication are considered as channel safety policies, and their effects are also measured using the models. The results suggest that the speed regulation scheme is effective in reducing accident risk in channels. It is concluded that methodology demonstrated and knowledge obtained in this study are useful for planning and safe operation of channels. PMID- 2222707 TI - The Hinton train disaster. AB - In February of 1986 a head-on collision occurred between a freight train and a passenger train in western Canada killing 23 people and causing over $30 million of damage. A Commission of Inquiry appointed by the Canadian government concluded that human error was the major reason for the collision. This report discusses the factors contributing to the human error: mainly poor work-rest schedules, the monotonous nature of the train driving task, insufficient information about train movements, and the inadequate backup systems in case of human error. PMID- 2222709 TI - Age-related differences in timing of position and velocity identification. AB - The aim of this investigation was to study age-related differences in timing of position and velocity identification in a laboratory task. The skills required for performing this task are thought to be similar to those needed in real traffic situations. From this perspective, the results of this study may be taken into account in studies on accident analysis and prevention. To control for differences in the conscious experience of time and for simple reaction time to visual stimuli, young (25-34) and old (58-70) adults had to produce timed periods of 20 seconds and to time the arrival of a visible moving object at its goal. In these simple tasks no differences were found between young and old subjects. In the proper, more complex experiment, timing of position and velocity identification of a moving object were assessed with or without feedback on timing and velocity in the same old and young group. The object, moving from left to right at a constant velocity, was shown on a video screen during the first 40% of its trajectory. The moving object could have any of four (fixed) velocities which were presented in blocks with a regular or a mixed order. By pushing a button subjects estimated at which time the object would have reached the marked end of a trajectory. In a condition without feedback on timing of position, the timing error of older adults was higher than that of young adults and particularly with higher object velocities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222708 TI - Pattern of organ injuries in pelvic fracture: impact force implications for survival and death in motor vehicle injuries. AB - The direction of force impact, lateral or frontal crash force, was estimated from the mechanism of pelvic fracture (PF) and related to the pattern of organ injuries, physiologic consequences, and outcomes in 197 motor vehicle accident (MVA) patients who had all sustained a PF. These data showed that injuries due to anterior-posterior compression (APC) (frontal crashes) were associated with injuries of major severity to the bony pelvis with major retroperitoneal bleeding and massive volume loss shock. Death in the APC patient was frequently due to a late complication of the shock: sepsis, adult respiratory distress syndrome (ARDS), or lung infection. However, in lateral compression (LC) injuries (lateral crashes) with fatal outcomes, there was a significant increase in severe brain injuries and a rise in lung and upper abdominal visceral injuries with relatively minor PF. These data suggest the great vulnerability of the MVA patient, driver or passenger, to lateral crash forces and suggest important areas for occupant protection. PMID- 2222710 TI - Safety analysis of manual tasks in automatic production systems--implications for design. AB - A safety procedure for application in the design of automatic production systems is outlined. It involves the specification on safety requirements for a particular system on the basis of general safety requirements and of the results of a safety analysis. During the safety analysis, work tasks inside the danger zone of the system and potential accident scenarios related to these tasks are identified, and safety measures are evaluated. Various checklists have been developed to support each step in the analysis. The method for safety analysis has been tested in field studies of three automatic production systems in operation: two mechanical systems and one process plant. The aim has been to evaluate the method and to collect operational experience concerning accident risks and preventive measures to be considered in design. The main results of the studies are presented, and considerations for the use of the method during the design phases are discussed. It is concluded that the approach that has been selected satisfies the needs of a safety procedure for use in design. PMID- 2222711 TI - A bivariate negative binomial model to explain traffic accident migration. AB - The phenomenon of "regression to the mean" is now widely known in the study of the effectiveness of remedial treatment of traffic accident blackspots. What happens is that the criterion used for selection of sites at which treatment is to be applied gives rise to bias in the estimate of the effectiveness: the conditional expectation of the after frequency is less than the true mean, even if the treatment is totally ineffective. It has been reported in some previous studies that accident "migration" has been observed. This is the phenomenon whereby the accident rate apparently rises at sites that are untreated but that are neighbours to treated sites. If this were a genuine effect, it would have serious implications for the assessment of remedial treatments. This paper aims to explain this migration effect in purely probabilistic terms, without recourse to the concept of physical migration. The model used is a new bivariate negative binomial distribution, incorporating spatial correlation between the true mean site accident rates. As with the regression to mean effect, the migration effect can then be explained in terms of the conditioning implicit in the selection process. PMID- 2222712 TI - Differences in accident characteristics among elderly drivers and between elderly and middle-aged drivers. AB - A total of 5,853 elderly drivers, aged 55 and over, and 8,210 middle-aged drivers 36-50 years old, all of whom were involved in accidents during 1986, were compared using discriminant function and univariate techniques. Substantial differences were found in accident characteristics not only between middle-aged and elderly drivers but also between three different age groups of the elderly. Support was found for the suspicion that, while the elderly have fewer accidents than younger drivers, their safety record, based on driving exposure with noncrash convictions as a surrogate measure of kilometres driven, is worse, and, in addition, they are more often at fault in accident involvements. PMID- 2222714 TI - Cardiac dysrhythmias during nasal surgery--a comparison with lignocaine adrenaline and prilocaine-octapressin during halothane anaesthesia. AB - The incidence of cardiac dysrhythmias and adequacy of haemostasis during nasal surgery under deep halothane anaesthesia were studied following nasal infiltration with 10 ml of either 1.5% lignocaine with adrenaline 1:200,000 or prilocaine 1.5% with octapressin 0.03 IU per ml. There was a significant difference in the incidence of cardiac dysrhythmias between patients given octapressin 2% and patients given adrenaline infiltration (18%) p greater than 0.01. Adequate haemostasis was observed in 84% of patients who received octapressin with no adverse effects compared to 94% of the group which received adrenaline (p greater than 0.01). We suggest for the use of lignocaine-adrenaline during halothane anaesthesia that adequate ventilation is assured, deep halothane anaesthesia given, the infiltration delayed 10 minutes after tracheal intubation, the rate of injection adjusted to 10 ml in a 10-minute period and a total dose of adrenaline does not exceed 0.6 microgram/kg. PMID- 2222713 TI - [Halothane hepatitis in the differential diagnosis of postoperative jaundice]. AB - Based on a case report the necessity of including halothane hepatitis in differential diagnosis of postoperative jaundice is described. Even in this case report, the diagnosis is a synopsis of the case history, clinical and biochemical findings and exclusion of other causes of disease. The detection of antibodies to halothane-altered hepatocyte components is at present only possible in a few special laboratories and does not succeed in all cases. Confirmation of the connection between halothane exposure and liver damage is of vital importance for the patient because a second exposure to halothane may result in fulminant hepatic failure. In choosing the appropriate anaesthetic method, other halothane anaesthesias carried out a short time ago should be considered. PMID- 2222716 TI - [The effect of barbiturates and diphenylhydantoin on the mitotic activity of thymocytes and bone marrow cells in mice and rats]. AB - Phenobarbitone (PB) and diphenylhydantoin (DPH) inhibited the mitotic rate of thymocytes and bone marrow cells (colchicine blocked metaphases) dose- and time dependent (20-80 mg/kg i.p., 12-48 hours) in mice and rats in vivo. The inhibition of proliferation was evident also after repeated administration of the drugs and other barbiturates. Other substances with a depressive effect on the central nervous system (etomidate, ketamine, chlorpromazine and ethanol) did not influence the mitotic rate of the thymocytes. Inhibition of the mitotic rate by PB was also observed in adrenalectomised rats. In vitro PB and DPH inhibited the mitotic rate of thymocytes in therapeutic and toxicologically relevant concentrations (10(-5)-10(-3) mol/l). The investigations indicate a direct effect of PB and DPH on rats. Possible immunosuppressive effects are discussed. PMID- 2222715 TI - [Equipment for respiratory gas conditioning under hygienic conditions]. AB - The significance of respiratory gas conditioning systems as sources of germ colonization and infection of the respiratory tract results from the principle of operation and the temperature. Six respiratory air humidifiers were tested for their hygienic risk in experiments with test germs. Contrary to several reports, some humidifiers were shown to accumulate microorganisms, whereas others do not promote germ population in the respiratory tract even though the water of the humidifier is heavily contaminated. It could be confirmed that basic differences exist between "blow over" and "blow through" humidifiers in the accumulation of microorganisms in respiratory air. Moreover, our investigations revealed that even "blow over" humidifiers should not be considered completely harmless. The "blow over" apparatuses Hydrotrop 200, Aquapor and VH 620 (infant) did not cause any germ propagation in the resuscitation tubes, whereas in the "blow through" apparatuses Bennett Cascade and VH 620 (adult) germ propagation is quite considerable. The mortality kinetics of the germs differ depending on the temperature and the type of apparatus used and should be taken into account when it comes to choosing or developing respiratory gas conditioning devices. Constant heating of the water in the humidifier to a minimum of 50 degrees C provokes a bactericide behaviour of the problem germs. Therefore, it is quite justifiable to do without expensive internationally recommended measures if the humidifier is well chosen. The requirement to replace the humidifier every 24 hours in long term artificial respiration need not be observed for devices classified as harmless if aseptic handling is guaranteed, i.e. if manual germ transmission by the staff is avoided. PMID- 2222717 TI - [The treatment of thoracic injuries from the anesthesiologic viewpoint]. AB - Three quarters of thoracic injuries are combined with other traumas, firstly head injuries, secondly injuries of the extremities and thirdly injuries of the abdomen. Seventy-one such patients who were treated in the interdisciplinary intensive care department over 6 years were analysed. In 13 patients laparotomies because of ruptures or perforations of various organs became necessary. These combined injuries had a particularly bad prognosis. Forty-six patients (64.7%) had to be ventilated for more than 24 hours. The average ventilation period was 10 days. The indication for respiratory treatment is stressed. The lethality of the 71 patients amounted to 32.4% (23 patients). During the first treatment even today simple methods of investigation and therapy are of great importance. A comprehensive rescue chain and good interdisciplinary cooperation are the basis of every therapy. PMID- 2222718 TI - [Bronchologic examination techniques for verifying abnormalities of the respiratory tract in early childhood]. AB - With appropriate technique of endoscopy and contrast radiography adapted to the age and the respective problem, specific bronchological examinations in all age groups are feasible. Of all endoscopic techniques for the diagnosis of abnormalities in the upper respiratory tract, the most suitable method is laryngotracheoscopy only with the optic under halothane insufflation anaesthesia with spontaneous respiration maintained. For combined malformations of the septum that are considered problematic in diagnosis, sounding is suggested to determine the location of the tracheoesophageal fistula and color scanning is recommended to prove patency, as well as simultaneous contrast radiography of the two systems. In bronchography the insertion of contrast medium via the elevated orotracheal tube has proved suitable for documentation and for a differentiated demonstration of the abnormality type. In the case of skeleton malformations of the respiratory tract and vessel abnormalities stenosing the bronchial tree, biplanar radiographs in both respiratory phases are imperative. PMID- 2222720 TI - [Computer-assisted management in emergency medical aid practice]. AB - After a two-year test period, a computer-aided analysis of the Emergency Medical Aid in Wolmirstedt was developed and has become an indispensable feature of the management structures. Using the computer detailed evaluation of speed, accuracy of diagnosis and suitable treatment is possible at short notice for basic medical and emergency needs. This information is available at all times. Twenty-five to 30 computer hours are necessary for recording and processing the results of 1,000 cases of EMA. The computer is not required for retrospective and analytical functions even in the control centre. However, for immediate solving of problems, e.g. the administration of risk patients and emergency regulations, the programme provides a considerable extension of general emergency treatment and is an inherent part of the EMA control centre. PMID- 2222719 TI - [A simple formula for calculating the CO2 flow in controlled hyperventilation of patients with solvent poisoning]. AB - Controlled hyperventilation is a therapeutic measure for the treatment of intoxications with solvents. To avoid the occurrence of respiratory alkalosis, carbon dioxide must be added to the inspiratory gas flow. Up to now the addition of carbon dioxide was performed empirically and was adapted to the needs by repeated blood gas analyses. We developed a formula enabling us to calculate the necessary carbon dioxide flow. A case report explains the procedure. PMID- 2222721 TI - [Preservation of homeostasis following the onset of brain death]. AB - One of the main problems faced by transplantation medicine is the lack of suitable donor organs. The success of organ transplantation depends on the quality of the organ to be transplanted. The initial function of the transplant depends on the quality of preparation. The aim of efforts after brain death is to maintain the morphological and functional integrity of the donor organ in situ. At our clinic, all potential organ donors undergo direct arterial pressure measurement and many receive a Swan-Ganz catheter. Catecholamine administration- varied on the basis of the hemodynamic parameters--is not associated with an impairment of organ function. Electrolyte determinations at 2-hour intervals and close laboratory controls are obligatory. These intensive-care measures are necessary because of the occurrence of severe metabolic and hemodynamic imbalances. A partly transient diabetes insipidus is the most frequent homeostatic disorder. In addition, severe electrolyte imbalances, disturbed glucose utilization and hypotension may be observed. Our investigations on the plasma concentration course of thyroid hormones, ACTH and cortisol after the onset of brain death suggest that the secretion of pituitary hormones is maintained until total necrosis of the pituitary gland occurs 30 to 40 hours later. The detection of circulating ADH up to 24 hours after the onset of brain death, despite the angiographically confirmed cessation of cerebral circulation, suggests that there may be a residual perfusion of hypothalamus and pituitary. The blood levels of epinephrine, norepinephrine and dopamine measured in brain dead patients not receiving catecholamines were in part considerably above the reference level. Our data suggest that vigorous intensive care management increases the number and quality of organs suitable for transplantation and reduces to a minimum the incidence of premature organ losses. PMID- 2222722 TI - Synthesis of 1-O-alkyl-2-O-methyl-glycerophospholipids with potential antitumor activity. AB - Some synthetic alkyl-lysophospholipid analogs have been described as a new class of immunopotentiating and antitumor agents. Among them, 1-O-octadecyl-2-O-methyl rac-glycero-3-phosphocholine has been reported to possess the highest antitumor activity. A new method for the synthesis of this compound and of the ethanolamine and serine-containing analog is reported. 1-Alkyl-2-methyl-rac-glycerol, prepared from 1,2-isopropylidene-glycerol, is phosphorylated and the intermediate is condensed either with N-t-BOC-protected ethanolamine or with N-t-BOC-protected serine benzhydryl ester. The choline-derivative is obtained by methylation with CH3I of the ethanolamine derivative. The same synthetic sequence has been used also for synthesizing compounds unsaturated at the fatty alkyl chain in position 1 of the glycerol moiety. Preliminary observation are reported on the selective cytolytic action of the compounds on a tumor cell line. PMID- 2222723 TI - 3,5-Diphenyl-1H-pyrazole derivatives. VI--Esters and 2-dialkylaminoethyl ethers of 1(2-hydroxy-2-phenylethyl)-3,5-diphenyl-1H-pyrazole and N,N-disubstituted 1-(2 amino-2-phenylethyl)-3,5-diphenyl-1H-pyrazoles with depressant and platelet antiaggregating activities. AB - The syntheses of 1-(2-hydroxy-2-phenylethyl)-3,5-diphenyl-1H-pyrazole 1 by reaction of 2-hydrazino-1-phenylethanol with dibenzoylmethane, of esters 2 and 2 dialkylaminoethyl ethers 3 starting from 1 as sodium salt and acyl chlorides or 2 chloroethyldialkylamines, respectively, as well as of N,N-disubstituted 1-(2 amino-2-phenylethyl)-3,5-diphenyl-1H-pyrazoles 5 by reaction of secondary amines with the tosylate of 1, are described. Some of the above compounds showed a considerable sedative effect in mice and a remarkable platelet antiaggregating activity in vitro, as well as moderate local anesthetic, analgesic and antiinflammatory activities in mice and rats. PMID- 2222724 TI - 3,5-Diphenyl-1H-pyrazole derivatives. VII--Esters, 2-dialkylaminoethyl ethers and N-substituted carbamates of 1-(2-hydroxy-3-phenoxypropyl)-3,5-diphenyl-1H pyrazole with depressant and platelet antiaggregating activities. AB - The syntheses of 1-(2-hydroxy-3-phenoxypropyl)-3,5-diphenyl-1H-pyrazole 2 by reaction of 1-hydrazino-3-phenoxy-2-propranolol with dibenzoylmethane, of esters 3 and 2-dialkylaminoethyl ethers 4 starting from 2 as sodium salt and acyl chlorides or 2-chloroethyldialkylamines, respectively, as well as of N-aryl carbamates 5 by reaction of 2 with aryl isocyanates, are described. Some of the above compounds showed a considerable sedative effect in mice and a remarkable platelet antiaggregating activity in vitro, as well as moderate local anesthetic, analgesic and antiinflammatory activities in mice and rats. PMID- 2222725 TI - Comparative in vitro dermatokinetics of ibuprofen (IBP). AB - IBP, a widely used non-steroidal antiinflammatory analgesic exhibits low solubility in acidic media (gastric environment) and inadequate pharmacokinetics when administered orally. Thus, IBP warrants investigation for better, more effective and faster localized therapeutic effect of the drug as an alternative to oral treatment. The potential of IBP of in vitro percutaneous uptake and dermal absorption was evaluated for possible topical therapy. IBP reservoir systems [IBP + various ointment bases] at various drug loading levels [doses: 200, 400 and 600 mg] were evaluated for drug release rate as well as mechanism of drug release. Additionally, recommendations were generated for rational development of optimally effective dermal products of IBP. IBP reservoir systems were evaluated for in vitro dermal uptake by employing modified franz diffusion cell. A semipermeable membrane was sandwiched between the donor compartment containing the IBP-reservoir system and the receptor compartment containing Sorenson's buffer at pH 7.4. The release rate of IBP was followed for 12 h. Release of IBP from various systems exhibited linear relationship with square root of time dependence indicating adherence to diffusional pathway. The rate of release of IBP increased with increase in drug load [dose]. Cumulative Qmax/Dose as a function of Dose was employed to generate recommendations for development of dermal product(s) for IBP. An oil-in-water system [Acid Mantle Creme (A/M Creme)] exhibited superior drug release characteristics over others in this investigation. This study demonstrated that IBP release characteristics can be effectively manipulated by incorporating changes in the system composition as well as drug loading. PMID- 2222726 TI - Nursing care of the paranoid patient. PMID- 2222727 TI - Legal considerations for psychiatric patients. PMID- 2222728 TI - Potassium replacement. PMID- 2222730 TI - Creative teaching with word puzzles. PMID- 2222729 TI - Learning with video. PMID- 2222732 TI - Ethics and deontology--a Soviet's point of view. PMID- 2222731 TI - Skin cancer--sun worship. PMID- 2222733 TI - Yugoslavian connection. PMID- 2222734 TI - Interviewing the elderly client. AB - Obtaining a health history is an important part of planning care for the elderly patient. Presented are facilitating methods that the nurse may use to make this process accurate and easy. PMID- 2222736 TI - Classes for the diabetic patient. A five day format. AB - This article discusses the material and presentation of a diabetic education program using a five day format. PMID- 2222735 TI - 13 ways to ease the nursing shortage. PMID- 2222738 TI - Nursing's image. A historical focus. PMID- 2222737 TI - Pericarditis. Nursing care makes the difference. AB - Nursing care of the patient with pericarditis, a commonly seen syndrome in the clinical setting, is discussed in this article. Pericarditis is particularly prevalent in the patient following myocardial infarction. Astute nursing assessment is described. Goals of nursing care include management of pain, maintenance of adequate cardiac output, and provision of support to manage anxiety and fear. Interventions to meet the goals, as well as outcome criteria, are identified. PMID- 2222740 TI - Don't believe everything you hear about instructor's reputations. PMID- 2222739 TI - Acute psychosis: a psychiatric emergency on medical surgical units. PMID- 2222741 TI - Neurovascular assessment. AB - This article discusses the process for monitoring a client's neurovascular status. Assessment of neurovascular status is monitoring the 5 P's: pain, pallor, pulse, paresthesia, and paralysis. A brief description of compartment syndrome is presented to emphasize the importance of neurovascular assessments. PMID- 2222742 TI - Culture and space. AB - This article focuses on personal space in a multi-cultural health-care environment by discussing each of the four aspects of spacial behavior from a nursing perspective: proximity to others, objects in the environment, body posture, and movement in the setting. PMID- 2222743 TI - DNA antibody idiotypes. An analysis of their role in health and disease. PMID- 2222744 TI - The characterization of DNA antibody idiotypes--a description. PMID- 2222745 TI - Immunopathology. PMID- 2222747 TI - Future directions in anti-DNA antibody idiotype research. PMID- 2222746 TI - Idiotype-mediated intervention in systemic lupus erythematosus. PMID- 2222748 TI - Comparison of DNA antibody idiotypes in human sera: an international collaborative study of 19 idiotypes from 11 different laboratories. AB - The distribution of and relationships between 18 anti-DNA antibody idiotypes and one anti-acetylcholine receptor antibody idiotype have been tested in an international collaborative study of human sera from 180 individuals. The main finding is that the serum levels of many of these idiotypes, whether of murine or human origin, show a high degree of statistical correlation. The studies in a wide range of autoimmune rheumatic diseases confirm that none of the idiotypes tested is disease specific, but 13 of 15 (87%) whose levels were recorded as OD units or cpm correlated strongly with anti-ssDNA antibody levels and 11 of 15 (73%) with total serum IgM. Expression of several idiotypes was found to fluctuate in parallel with disease activity in SLE; levels of others were also elevated in the healthy relatives of lupus patients whilst a few were also raised in the spouses of these patients. The data support the notion that there may be only a few groups of related DNA antibody idiotypes. The correlations between the idiotypes with regard to their quantities, association with disease activity, and wide distribution in different diseases and healthy individuals suggest at least two explanations. First, all of these idiotypes may be present in normal immunoglobulin repertoires and simply increase in response to poly- or oligoclonal B-cell activation in autoimmune diseases. Secondly, these idiotypes may be structurally linked to each other, so that their behaviour under conditions of specific antigenic stimulation is similar. Genetic and structural studies will be required to distinguish between these possibilities. PMID- 2222749 TI - Comparative study of idiotypes on monoclonal antibodies derived from patients with lupus and leprosy and from normal individuals. AB - A collaborative study was performed to compare the expression of a series of idiotypes defined on human anti-DNA and other autoantibodies. Three panels of human monoclonal antibodies were tested: eight derived from patients with systemic lupus erythematosus (SLE); 13 from an individual with lepromatous leprosy; and 38 from normal subjects. The following rabbit anti-idiotype sera were used: one (RId16/6) raised against the lupus-derived monoclonal anti-DNA antibody 16/6, four (RId8E7, RId4G7, RId4D5 and RIdTH9) against leprosy-derived monoclonal antibodies of various specificities, and one (anti-4.6.3) against a normal-derived anti-DNA monoclonal (KIM 4.6). In addition, two other anti idiotypes were used--one a murine monoclonal (3I), the other a rabbit polyclonal (RIdD)--which had been raised against polyclonal anti-DNA antibodies from lupus serum. Further experiments were performed with immunoabsorbed fractions of RId8E7. Direct-binding and competition assays were used. All of the anti idiotypes produced different patterns of positivity among the three panels of human monoclonal antibodies, with the exception of RId8E7 and RId4G7, which showed considerable concordance. There was a tendency towards anti-idiotypes being disease- or group-specific: thus anti-4.6.3 failed to bind to any of the lupus or leprosy-derived monoclonals, while RId16/6 and RId8E7 bound most strongly to the lupus- and leprosy-derived antibodies respectively. KIM 4.6 itself was bound only weakly by RId16/6, while 16/6 was not recognized by anti 4.6.3; 16/6 was, however, bound by 3I, while KIM 4.6 was not. 3I bound to several other monoclonals but RIdD, which has been shown to be specific for the anti-DNA fraction of lupus serum, did not bind to any of them. These results indicate that the majority of these anti-idiotype preparations recognize largely separate sets of determinants. The monoclonal antibodies which bind to DNA may be only partly representative of anti-DNA antibodies in the serum of lupus patients. PMID- 2222750 TI - Evidence for a role of anti-idiotypic antibodies in the induction of remission in Graves' disease. AB - Serum and Ig samples obtained from a patient with Graves' disease during exacerbation and remission were evaluated in the nu/nu bioassay. Blocking of the exacerbation serum's biological activity was demonstrated by several biological assay parameters after it was mixed with the remission serum. Since this blocking effect can be ascribed to immunoglobulins, anti-idiotypic antibodies in the remission serum and immunoglobulin samples are the most likely cause of this blocking effect. Therefore a role of anti-idiotypic antibodies in the induction of remission in Graves' disease is postulated. PMID- 2222751 TI - Differential regulation and expression of major histocompatibility complex (MHC) and Ly-6 gene products on mouse testicular Leydig and Sertoli cell lines. AB - The expression and regulation of Class I and Class II major histocompatibility complex (MHC) and Ly-6 antigens were examined in BALB/c testicular cells. Studies were performed utilizing differentiated murine Leydig (TM3) and Sertoli (TM4) cell lines. Neither Class I (Dd) nor Class II (IA/Ed) MHC antigens were detectable on untreated TM3 cells. However, concanavalin-A activated spleen cell supernatant (Con-A sup) or interferon-gamma (IFN-gamma) treatment resulted in the marked induction of both Class I and Class II MHC antigens on virtually all of the Leydig cells. MHC Class II mRNA, which was not detected in resting cells, was clearly induced following IFN-gamma incubation. Sertoli cells were found to constitutively express low levels of Class I (Dd) but not Class II (IA/Ed) antigens. However, in contrast to the enhanced MHC expression in TM3 cells, Con-A sup or IFN-gamma treatment of TM4 cells resulted in marked augmentation of Class I, but not Class II, MHC antigens. Northern blot analysis failed to detect Class II mRNA in either the resting or IFN-gamma treated TM4 populations. Neither ethanol nor tumor necrosis factor (TNF) alone, or together with IFN-gamma head significant effects on MHC expression by TM3 and TM4 cells. Ly-6 antigens, predominantly expressed on hematopoietic cells, were found to be present on both TM3 and TM4 cells. Expression of this non-MHC encoded product was also shown to be markedly enhanced by IFN-gamma treatment on both testicular cell lines. In total, these findings demonstrated that cytokines can differentially affect discrete cell populations arising from a particular tissue with respect to the un regulation of MHC and non-MHC gene products. These findings are discussed in the context of autoimmune responses directed against this tissue. PMID- 2222752 TI - Identification of the platelet glycoprotein IIb/IIIa complex as a target antigen in primary biliary cirrhosis-associated autoimmune thrombocytopenia. Evidence that platelet-reactive autoantibodies can also bind to the mitochondrial antigen M2. AB - A 67-year-old woman with a 4-year history of primary biliary cirrhosis (PBC) unexpectedly developed autoimmune thrombocytopenia. The platelet-bound IgG antibody was eluted from the patient's platelets to determine the platelet target antigen. The autoantibodies were found to precipitate the platelet glycoprotein complex IIb/IIIa of autologous and allogeneic platelets. A further precipitate of 70 kDa was detectable under reducing conditions. In addition, platelet-reactive antibodies bound to the 70 kDa mitochondrial antigen M2. No cross-absorption studies were performed to confirm that a single antibody reacted with both antigens. Computer analysis of published peptide sequences of the mitochondrial protein and the platelet GPIIb/IIIa complex showed partial amino acid sequence homology suggesting the possibility of a common antibody binding site. These findings suggest a relationship between the development of autoimmune thrombocytopenia in PBC and the underlying liver disease. PMID- 2222753 TI - [Malocclusion in the primary dentition]. AB - In this paper we analyze the type and frequency of malocclusions in a group of 100 health children with complete primary dentition. Bjork's method for epidemiological registration was taken as a basis. Of the examined children, 78% had some malocclusion type. The most frequent was the increased horizontal overbite. In vertical overbite relation we find anterior open bite, increased overbite, anterior open bite, increased overbite. PMID- 2222754 TI - [Stages of formation and calcification of the third molar (radiographic study of 500 Mexican children and adolescents)]. AB - Five hundred orthopantomograph radiographs of mexican children and adolescent from 7 to 18 tears old were reviewed in order to establish the third molar formation and calcification stages and the most frequent anomalies related to these teeth. We find that tooth bud presence is between 9 and 11 years; Third molar is absent in 32.4% of the population; 7.4% of the molars presented early formation stage malposition; Therefore oligodontia diagnosis and third molar malposition can not be done before 13 years of age. PMID- 2222755 TI - [Panoramic radiograph in the pediatric radiographic examination]. AB - In the present time the high value of panoramic radiography on diagnosis is recognized in all odontology areas. Panoramic radiography shows in one picture upper and lower arches and numerous adjacent structures that is why it has a special value in pediatric patient radiography examination. PMID- 2222756 TI - [Degree of sedation. Incidence of vomiting and time of postoperative sleep with 3 different oral administration schedules of hydroxyzine chlorhydrate and chloral hydrate]. AB - In this paper a comparison of sedation effectiveness, vomiting incidence and postoperative sleeping time with three sedation schemes: Chloral hydrate exclusively, hidroxicine chlorhydrate the night before and 15 minutes before chloral hydrate administration and hidroxicine chlorhydrate 15 minutes before chloral hydrate. We find that there is no significant differences between these three sedation schemes in sedation, degree of postoperative sleeping time and vomiting incidence, therefore we can expect an effective sedation degree using any of these sedation methods. PMID- 2222757 TI - In support of IL-8. PMID- 2222758 TI - Humoral effector mechanisms in the immunity to cancer. PMID- 2222759 TI - Anti-metatype antibody reactivity: a model for T-cell receptor recognition. AB - Anti-metatype (Met) antibodies are anti-immunoglobulins that specifically recognize an antibody-liganded active site but lack specificity for either the ligand or the idiotype. As proposed here by Edward Voss, anti-metatype-metatype immunoglobulin interactions may serve as a model for the interaction of the T cell receptor (TCR) with antigen-MHC (class I/class II) complexes: the anti metatype immunoglobulin reagent simulates the TCR and the liganded antibody mimics the antigen-MHC complex. Such a model addresses the dilemma of two macromolecules interacting with the same antigenic determinant and may represent a rational approach to improve understanding of the initiation and regulation of the immune response. PMID- 2222760 TI - The role of thymic epithelium in the acquisition of tolerance. AB - There are two separate mechanisms of induction of T-cell tolerance in the thymus. First, MHC molecules expressed on bone-marrow-derived cells can cause clonal deletion of autoreactive cells. Second, as discussed here by Elisabeth Houssaint and Martin Flajnik, thymic epithelial cells can generate a form of tolerance that does not eliminate self-reactive clones. This nondeletional mechanism, which is also a feature of the other MHC class-II-bearing epithelia, may contribute to the establishment of tolerance-maintaining regulatory networks. PMID- 2222762 TI - [Dermatitis from contact with perfume]. AB - Contact dermatitis essentially involves those areas to which perfume is applied. The mixture of perfumes in the standard battery of the L.C.D.R.G. detects 70 to 80% of sensitised cases. The allergens that are most often involved are oak moss, isoeugenol and cinnamic aldehyde. Prevention of dermatitis requires, at individual level, use of non-perfumed cosmetics and at the industrial level, good observance of the international rules of I.F.R.A., aimed at limiting the frequency of occurrence. PMID- 2222761 TI - Allelic variations of human TCR V gene products. AB - A central problem confronting the immune system is how to discriminate among vast numbers of antigens. Novel genetic ploys that aid the discriminative process, including complex gene rearrangements (in antibody and T-cell receptor (TCR) genes) and extensive allelic polymorphism (in major histocompatibility complex (MHC) genes), have been described. Recent evidence has suggested a further level of diversity; TCR V gene allelic variation. In this article David Posnett summarizes evidence in favour of this possibility and speculates on the possible functional consequences of TCR allelism. PMID- 2222763 TI - [Diagnosis of dermatitis due to plants]. AB - Contact dermatitis from plants may occur by several mechanisms. It may arise as a result of simple irritation or by allergic mechanism; co-exposure to sunlight can evoke the phenomena of phototoxicity or photoallergy. Etiologic diagnosis require botanical, chemical and immunologic knowledges. Patch testing can be performed with pure allergens (primin, sesquiterpene lactones etc.), plant extracts (balsams, oleoresins etc.) or with the plant itself. The validity of patch test results is often difficult to determine: false positive reactions due to the presence of pesticides or herbicides, active sensitizations, cross-reactions. PMID- 2222764 TI - [Research on Kathon CG in cosmetic and personal hygiene products]. AB - Kathon is an anti-microbial agent that is used as a preservative in cosmetics and bodily hygiene products. At the recommended levels of usage Kathon is innocuous and has a recognised efficacy. Nevertheless, following reappearance of contact allergic eczemas due to cosmetics and bodily hygiene products different authors have reported increase in sensitisation to it. We have met the same problems in the Service de Dermatology++ of the Hospital Sainte Marguerite at Marseille and we wished to make a deeper examination of the question and to ascertain whether the current cosmetics contained Kathon CG. For this we have developed a technique of liquid chromatography and tested 44 creams. Eight contained Kathon CG, of which 2 were responsible for contact eczema in patients. PMID- 2222765 TI - [Importance and limits of assay of TNF in pathology]. PMID- 2222766 TI - [Rhinitis in a child induced by aspirin and by cow's milk]. PMID- 2222767 TI - An assessment of a film enhancement system for use in a radiation therapy department. AB - The clinical uses of a radiotherapy film enhancement system are explored. The primary functions of the system are to improve the quality of poorly exposed simulator and portal films, and to perform comparisons between the two films to determine whether patient or block positioning errors are present. Other features include: the production of inexpensive, high quality hardcopy images of simulation films and initial portal films for chart documentation, the capacity to overlay lateral simulation films with sagittal MRI films to aid in field design, and a mode to zoom in on individual CT or MRI images and enlarge them for video display during chart rounds or instructional sessions. This commercially available system is comprised of a microcomputer, frame grabber, CCD camera with zoom lens, and a high-resolution thermal printer. The user-friendly software is menu driven and utilizes both keyboard and track ball to perform its functions. At the heart of the software is a very fast Adaptive Histogram Equalization (AHE) routine, which enhances and improves the readability of most portal films. The system has been evaluated for several disease sites, and its advantages and limitations will be presented. PMID- 2222769 TI - Blood irradiation: rationale and technique. AB - Upon request by the local American Red Cross, the Savannah Regional Center for Cancer Care irradiates whole blood or blood components to prevent post transfusion graft-versus-host reaction in patients who have severely depressed immune systems. The rationale for blood irradiation, the total absorbed dose, the type of patients who require irradiated blood, and the regulations that apply to irradiated blood are presented. A method of irradiating blood using a linear accelerator is described. PMID- 2222768 TI - Clinical applications of a CT-simulator: precision treatment planning and portal marking in breast cancer. AB - Breast cancer is frequently treated with radiation using opposed tangent portals to the involved breast, including the chest wall. Presented is a method for simulating such treatment fields on a CT simulator. A short series of CT images provides a three dimensional model for treatment planning prior to marking the patient. Gantry and collimator angles, as well as wedges or custom blocks, are determined in the planning stage. Upon receipt of an approved treatment plan, the portals are available for simulation. The cross-hair laser and computerized bed movement in the CT simulator aid in marking the entrance of the radiation fields on the patient's skin. Discussion of the clinical application of the described technique is included. PMID- 2222770 TI - The use of digitized port films in assessing new treatment modalities. AB - An inexpensive computer-based imaging system has been used to compare simulator and portal radiographs. The films were digitized, normalized, and then overlaid for measurement. In a test group of patients, a new treatment protocol for pelvis irradiation was evaluated using this technique. For 90% of the patients, the average error was found to be smaller than 5 mm, and there were no field placement errors greater than 1 cm. PMID- 2222771 TI - Cadmium free lead alloy for reusable radiotherapy shielding. AB - A low melting point cadmium free fusible lead alloy suitable for custom radiotherapy shielding blocks is described. The alloy, referred to here as Alloy 203, differs in composition from the more common Lipowitz's metal (Cerrobend) by being cadmium free, having a slightly higher lead content and a 203 degrees F melting temperature. Attenuation properties have been studied for 4-18 MV X-rays. Alloy-203 has lower transmission than Lipowitz's metal, primarily due to the higher content of lead and bismuth. Daily use for the past 2 years at Mayo Clinic has not indicated any major problems associated with the use of this cadmium free alloy for custom shield fabrication. PMID- 2222772 TI - A unique nasopharynx brachytherapy technique. AB - To deliver a curative dose of radiation therapy to the nasopharynx using either external beam radiotherapy or conventional brachytherapy, it is often necessary to expose a large volume of normal tissue. Tolerance of normal tissue also limits the dose of radiation given for salvage therapy in failed nasopharyngeal carcinoma. A unique brachytherapy technique with associated treatment planning is presented as an alternative method of treatment. This technique combines a single linear cesium-137 source inserted in the nasopharynx via a modified cuffed endotracheal tube, in conjunction with a plaque of iridium-192 ribbons applied in the form of a modified upper denture appliance. This method allows additional treatment to the primary area while neither exposing more normal tissue than necessary nor exceeding tolerance doses to surrounding structures. PMID- 2222773 TI - Implementation of Beam's Eye View into routine treatment planning and delivery. AB - The use of oblique fields in the chest and abdomen is fraught with uncertainty, especially in the location of critical structures on simulator and port films. Targets near these structures may be underdosed because of the physician's uncertainty in shaping the treatment fields. To help alleviate this problem, we have found the Beam's Eye View option of the Theraplan Treatment Planning System to be a useful and effective tool. The Beam's Eye View program uses the external and internal contours we enter into the treatment planning system from CT scans. Once the necessary contours have been entered from the desired CT slices, the software will project the view that the beam would see as it passes through these structures. Using this "Beam's Eye View," we can determine the optimum angle and field shape to treat our target and minimize critical structure dose. PMID- 2222774 TI - Progesterone suppression of pregnancy lymphocytes is not mediated by glucocorticoid effect. AB - This study investigated whether the suppressive effect of progesterone on pregnancy lymphocytes is mediated by specific progesterone receptors. The effects of a competitive progesterone antagonist (RU486) and a specific glucocorticoid receptor blocker (RU43044) were tested on the release of a blocking factor by progesterone-treated pregnancy lymphocytes. RU 486 tested at an equal concentration as progesterone significantly inhibited the production of the blocking factor, while RU 43044 was without effect. These data suggest that in pregnancy, lymphocyte progesterone acts on specific progesterone receptors and glucocorticoid binding sites are not involved. PMID- 2222775 TI - Hydatidiform mole pregnancy trophoblast extracts differentially suppress interleukin-2-induced proliferation of human T-lymphocytes and PHA-blasts. AB - Immunoregulatory factors of trophoblast origin may partially abrogate maternal immune responses to the fetus during pregnancy. We have previously shown that soluble factors extracted from hydatidiform mole trophoblast suppress interleukin 2 (IL-2)-dependent proliferation of a cloned murine cytotoxic T cell line (CTLL 2). To characterize human T cell responses to this trophoblast extract, we measured the effects of molar tissue extracts (HME) on IL-2-stimulated proliferation of human T-lymphocytes and mitogen (PHA) transformed T-cell blasts (PHA-blasts). HME significantly (P less than 0.05) suppressed T-lymphocyte proliferation in response to 5 and 10 units/ml of IL-2 at 500 and 250 micrograms/ml, while no effect was observed at the 100 micrograms/ml concentration. Suppression by HME of IL-2-stimulated T-cell proliferation was partially overcome by the addition of excess IL-2. HME also suppressed (P less than 0.05) IL-2-stimulated proliferation of PHA-blasts at 500 and 250 micrograms/well at both 5 and 10 units/ml of IL-2. As observed with resting T cell responses, no suppression of PHA-blast proliferation was observed using 100 micrograms/ml of HME. In contrast to the response of the resting T-cells to excess IL-2, HME suppression of IL-2-stimulated blast proliferation was not affected by increasing the concentration of IL-2. These results indicate that extracts from hydatidiform mole trophoblast contain immunosuppressive factors that block human T-cell clonal expansion by inhibiting the utilization and/or production of IL-2. Furthermore, the effects of HME are not reversed by excess IL 2 when PHA-blasts are reacted compared to resting T-cell responses, which are partially reversed in the presence of excess IL-2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222776 TI - The detection of antibodies in pregnancy: a comparison of two assay systems. AB - In this study we have compared the ability of two assay systems, erythrocyte antibody rosette inhibition (EAI) and cellular enzyme-linked immunospecific assay (CELISA) to detect maternal alloantibody activity during pregnancy. Antibody activity to antigens on paternal lymphocytes was present in nine of 23 primigravid sera tested by EAI and in seven of 23 by CELISA. In multiparous sera, antibodies directed to paternal lymphocytes were detected in 11 of 15 individuals by EAI and in six of 15 by CELISA. The techniques correlated significantly when assaying the humoral response in sera from multiparous women. The lack of correlation when assaying primigravid sera suggests that both assays encounter difficulty in detecting the low titres of antibodies present. PMID- 2222777 TI - Nidation, tolerance, and immunotrophism. PMID- 2222778 TI - Human seminal plasma suppresses the chemiluminescence of polymorphonuclears without modifying phagocytosis. AB - The suppressive activity of human seminal plasma was confirmed on the luminol amplified chemiluminescent reaction of human polymorphonuclears. This suppression was found to be dose-dependent and noncytotoxic. The responsible factor appeared to be a radical scavenger of low molecular weight, acting selectively on hydrogen peroxide. Correlation with glandular markers of semen indicated this molecule to have a prostatic origin. Neither crude seminal plasma nor this factor were found to suppress intracellular engulfment and killing of bacteria. This molecule seems to cooperate with the other semen antioxidants to protect sperm cells from extracellular oxygen radicals. PMID- 2222779 TI - Multiple effects of tetrahydroaminoacridine on the cholinergic system: biochemical and behavioural aspects. AB - 9-Amino-1,2,3,4-tetrahydroaminoacridine (THA) in combination with lecithin has been reported to improve the memory of Alzheimer's disease patients. We have examined some properties of THA in vitro and in vivo so as to define some of the mechanism(s) by which THA might produce its therapeutic effects. In vitro, THA was more potent at inhibiting human plasma cholinesterase (IC50 = 0.03 microM) than human erythrocyte acetylcholinesterase (IC50 = 0.3 microM) and rat brain acetylcholinesterase (IC50 = 0.32 microM). Radioligand binding studies indicated that THA binds reversibly and competitively to primary M1 and M2 human cortical muscarinic receptors with similar affinities. Moreover, THA showed similar affinity for temporal cortices muscarinic receptors from Alzheimer and non Alzheimer (control) brains. In vivo, subcutaneous administration of THA (1-8 mg/kg body weight) to adult rats (6 months old) produced a dose dependent decrease in general activity compared to saline-treated rats. However, at a concentration of 0.5 mg/kg body weight, the general activity of the rats was increased compared to saline-treated rats. The cognitive function of the THA treated adult rats (subcutaneously 2 mg/kg body weight) was not significantly improved compared to saline-treated rats. It is concluded that the mechanisms of action of THA on the cholinergic system involve reversible inhibition of cholinesterases and reversible and competitive interaction with muscarinic acetylcholine receptors. These effects might be of therapeutic value in the treatment of Alzheimer's disease. PMID- 2222781 TI - Increased platelet 3H-imipramine binding and monoamine oxidase B activity in Alzheimer's disease. AB - Several biochemical abnormalities in peripheral tissues have been reported in Alzheimer's disease (AD). With this in mind we studied platelet monoamine oxidase B (MAO B) activity and 3H-imipramine (IMI) binding in both AD patients and healthy subjects and found a significantly higher level of platelet MAO B activity and 3H-IMI Bmax values in the AD patients. In view of the part that MAO B plays in metabolizing serotonin (5HT) and of the relationship which exists between 3H-IMI binding and 5HT uptake, our results would suggest that with AD there occurs a complex dysfunction in the 5HT system, at least at a peripheral level. PMID- 2222780 TI - 5 HT2 receptors in dementia of Alzheimer type: a quantitative autoradiographic study of frontal cortex and hippocampus. AB - Using both quantitative autoradiography in sections and a homogenate preparation assay, the distribution and density of 3H-ketanserin binding to 5 HT2 receptors was examined in frontal cortex and the hippocampal region from six control subjects and seven subjects who had dementia of the Alzheimer type (DAT). There was no difference between control and DAT subjects in the levels of ketanserin binding in any region of the frontal cortex or hippocampus determined by quantitative autoradiography or in parallel experiments using homogenate preparations (e.g. left frontal cortex, layer III; controls, 34.4 +/- 1.6 pmol/g, DAT, 37.1 +/- 4.6 pmol/g). In all of the DAT brains there were abundant neuritic plaques (e.g. superficial layers of left frontal cortex; 35 +/- 7 plaques/mm2), and a marked reduction of choline acetyltransferase activity, (by 30-60% relative to controls), in both frontal cortex and the hippocampus. Thus, despite the presence of morphological abnormalities and a loss of cholinergic function, two classic features of DAT, 5 HT2 receptor binding was unaltered in this group of DAT brains compared to controls. PMID- 2222782 TI - [Status determination in discussion of benign stenosis of Vater's papilla]. AB - Inflammatory and cicatrical alterations are the morphological basis of papillary stenosis in most cases due to canalicular or lymphatic spreading of bacterial infection in gallstone disease. The consequences of papillary stenosis are elevated pressure in the ducts and reduced bile flow. At surgery you find dilatation of the bile ducts, increase of residual pressure, decrease of outflow, and--in cicatrical stenosis--stop for the probe. Only the inflammatory stenosis is reversible, but permanent alteration is not to determine. Therefore therapy is necessary, at first instrumental dilation to 4-6 mm. Impossibility of dilatation indicates transduodenal sphincterotomy. Recurrencies are best treated by endoscopic sphincterotomy and exceptionally by choledochoduodenostomy. PMID- 2222783 TI - [The 25th anniversary of the East German Society of Gastroenterology. II. Development of the concept of the gastroenterology subdiscipline]. AB - As like as the introduction of the gastric tube inaugurated new possibilities of investigation, the concept of gastroenterology was rounded up by the study of physiology and pathology of gut, liver, bile-ducts, and pancreas. In form of X ray examination, topographic gliding palpation, and endoscopy, gastroenterology gained valuable diagnostic methods. The development confirmed Boas' prediction that specialization in the end is for the benefit of total science. PMID- 2222784 TI - [Pathogenetic factors of hemorrhage from esophageal varices]. AB - Esophageal varices nearly always rupture at or just above the gastro-esophageal junction. Mucosal changes on top of the varices, the so-called red colour sign, are found in the majority of patients with a positive bleeding history. An increase of intraabdominal pressure and consequently a sudden pressure rise in the varices is thought of as a trigger cause. The larger the esophageal varices the higher the intravariceal and the transmural varix pressures. The portal pressure in patients with portal hypertension is subjected to considerable changes. Therefore, hemodynamic measurements at rest may have a prognostic value with regard to predisposition to hemorrhage, but they are less significant than endoscopic parameters. Disturbances of blood hemostasis and ascites indicating an impaired liver function are essential predisponable factors for the onset of bleedings. A peptic lesion caused by acid gastric-esophageal reflux is of less importance for the occurrence of variceal hemorrhage. PMID- 2222786 TI - [Endoscopic treatment of acute biliary pancreatitis]. AB - The authors examined the possibilities of the endoscopic treatment of acute gallstone pancreatitis on the basis of the results of retrospective investigation of 19 middle-european endoscopic centers. There were altogether 11,830 EST in these centers; in 261 out of them the indication of EST was acute gallstone pancreatitis. They consider the exact and early diagnosis very important that can be based on the typical clinical and laboratory signs and ultrasonography. The ERCP reassures the final diagnosis and at the same time the therapeutic solution- EST--can also be realized. This took place within the first 48 hours. The results were favourable, in 90.4%, the complaints decreased significantly within 24 hours. The complication rate was 4.9%, and the mortality rate was 1.9%. These results are better than those of the conservative therapy. PMID- 2222785 TI - [Behavior of postoperative viscosity of bile fluid from T-drainage. A contribution to cholelithogenesis]. AB - The results obtained by the examination of the post-operative bile viscosity behaviour sampled by T-drainages of 29 patients (investigations of the relative viscosity with the help of a modified horizontal capillary viscometer from the day of operation until the 9th postoperative day) confirm the importance of the biorheological classification of bile fluid as a Maxwell fluid (investigations of the absolute dynamic viscosity of 33 bile specimens with a Contraves-Low-Shear Viscometer and representation of flow curves for rheological characterization). The Maxwell flow behaviour is characterized--among other things--by an exponential increase in the case of prestasis. This fact is important in all "low flow-states" of different pathophysiological genesis and offers a concept with respect to a pathogenetically orientated cholelithiasis prophylaxis. PMID- 2222788 TI - [Complications of hepatic coma in liver cirrhosis]. AB - 59 patients with exogenous liver coma in state III-IV were treated from 1980 to 1989 in our clinic. Incidence and complications in these patients were evaluated retrospectively. The most frequent eliciting factors were gastrointestinal bleeding, infections and acute alcohol excess, more than 2/3 of them having severe portal hypertension with ascites and esophageal varices at the time. Altogether 55 of the 59 liver coma patients died. The most important complications were, beside bleeding and infections, disturbances of the renal function and of the coagulation. Severe acute or chronic liver injury is often associated with multiorgan failure. PMID- 2222787 TI - [Prevalence of cholelithiasis in relation to use of hormonal contraceptives]. AB - 400 women in continuous care of a family planning clinic were examined for gallbladder stones by standard ultrasound technique. Gallstones (GS) are found infrequently in nulliparous women (3.1 percent). The prevalence of GS increases with number of births and with age: 11 percent of female under 25 years of age, who have ever born, have GS; women aged 45 years and older who have born two or more children have GS in 35 percent. Duration of use of HC increases with rising age and with number of births. There is no regular relationship between duration of use of HC or total dose respectively and prevalence of gallbladder stones. CONCLUSION: Intake of HC has no or only a marginal influence on prevalence of gallbladder stones. PMID- 2222789 TI - [Effect of an angiogenesis-promoting dipeptide on microcirculation in experimental chronic stomach ulcer in the rat]. AB - The influence of an angiogenesis stimulating dipeptide (Lys-Pro-derivative) on the blood flow rate of the stomach was tested in rats suffering from ulcus ventriculi by microspheres technique. 21 days after operation (acetic acid model by Takagi) the ulcers in the group treated with the dipeptide were healed completely, but not in the control group. The higher blood flow in the ulcer area of the dipeptide group radiometrically gained, was not changed significantly (U test by Man-Whitney). These results demonstrate, that the process of rapid wound healing promoted by the dipeptide cannot entirely be explained by a higher blood flow of the stomach. PMID- 2222790 TI - [Metoclopramide antagonizes dopamine-induced inhibition of lower esophageal sphincter pressure in the awake beagle]. AB - Different contradictory results, even in the same species of the DOP-effect on LESP have been reported. The aim of the present studies was to evaluate the effect of DOP on LES in purebread male beagles and whether in could be antagonised by the DOP-antagonist MCP. The LESP in beagles is sensitive to dopamine (DOP) and its "antagonist", metoclopramide (MCP). MCP raised the inhibited LESP after DOP-infusion in vivo, while it failed to change DOP-induced relaxation of opossum LES in vitro [1]. Data obtained after monotherapie with MCP did not exceed LESP-response to MCP after DOP-pretreatment. DOP applied as background counter-inhibition could be used to correct interdigestive phasic changements of LESP in order to reach a stable starting-point to investigate the action of LESP-stimulating compounds pharmacomanometrically. Due to DOP reflux facilitating side effect via its decrease of LESP, large doses of DOP, as used in the intensiv care unit, should be administered together with sphincter strengthening agents or antacid compounds. PMID- 2222791 TI - [Combination of glandular and foveolar hyperplasia of the gastric mucosa--a rare mixed type]. AB - In a 28 year-old man with epigastric pain endoscopy detected giant gastric folds and multiple superficial erosions. Histologically a mixed form of glandular and foveolar hyper plasia of the gastric mucosa was suggested (Ming's type III). Basal and pentagastrin stimulated secretion volume and acid output were moderately elevated, hypersecretion of protein was not found. Serum levels of calcium and gastrin were normal, also after secretin stimulation. The mucosa of the corpus was extensively infested with Campylobacter pylori. Therapy with cimetidine, antacids, pirenzepine and metronidazol resulted in relief of symptoms but not of histological findings. Bismuth (JatroxR) was successful in eradicating Campylobacter pylori and decreasing inflammation of the mucosa. Cause and prognosis of this mixed hyperplasia are not known. PMID- 2222792 TI - A different kind of clinical evaluation instrument for use in a programme in radiography. AB - Clinical evaluation of radiography students during their performance of non routine radiographic examinations can be quantified if the proper instrument is used. Such an instrument, referred to as the non-routine radiography examination evaluation by radiographic science faculty at Idaho State University, requires the student to perform a variety of atypical radiography examinations including trauma, paediatrics and portables. This particular instrument provides a mean of documentation and evaluation in an area of student competency which can otherwise be difficult to assess and evaluate. PMID- 2222793 TI - Methods for teaching effective patient communication techniques to radiography students. AB - Teaching students to communicate effectively with patients has always been part of the radiography curriculum in the USA. However, developing these skills has become even more important in recent times due to several factors. Patients who have been well versed in what to expect from the examination being conducted are in a better position to co-operate with the radiographer. This increases the chances of producing optimal results from an examination at the first attempt, thus reducing radiation exposure, patient discomfort and the overall cost of conducting the procedure. Also, increased competition among health care providers has resulted in more emphasis being placed on patient, or customer, satisfaction. Radiographers are in the 'front line' of patient care. Patients often have more interaction with radiographers than with physicians or other medical specialists. Radiographers who practise effective communication techniques with their patients can alleviate anxiety and make an important contribution to the overall satisfaction of the patient with respect to the quality of service and care they receive. This article describes instructional methods being used in the USA to help develop effective patient communication techniques, and reports the findings of a study among radiography educators as to which of these methods are thought to be most successful. PMID- 2222794 TI - Ultrasound of the acute abdomen--Part III. PMID- 2222795 TI - Digital spot-film fluorography. AB - Initial assessment of the DSI unit proved the ergonomic advantages of the system compared with a conventional fluoroscopic/fluorographic system. Also, a decrease in radiation dose levels proved encouraging. Savings in respect of hard copy expenditure and higher patient throughout area which the DSI technique can exploit. However, spatial resolution is still not equal to that of conventional film/screen imaging, but the 1024 matrix option and the facility for post processing of the images in terms of contrast, brightness and edge enhancement have produced diagnostically acceptable images for all examinations undertaken (see figures 4 and 5). PMID- 2222796 TI - Amperometric immunoassay. AB - An exciting new analytical technique based on amperometric devices used to measure immunoassays is reviewed in this article. The utility, ease, speed, simplicity, and many other advantages of performing amperometric immunoassays (AIAs) are discussed throughout the review. Limitations are also described, with electrochemical comparisons being made between AIAs and other conventional analytical methods, including potentiometric immunoassays. The review essentially consists of a general AIA overview, followed by sections devoted to amperometric electrode types, assay design, basic principles, automation, application, and future use. Operational features of oxygen gas selective electrodes and oxidoreductase probes are discussed for a better understanding of AIA principles. Characteristics, limits, advantages, and disadvantages of these different devices are presented. A variety of homogeneous and heterogeneous AIAs are described, together with many applications of the different assay formats available. AIAs are classified according to the electrode type employed, enzyme labels required, or electrochemical components involved. Important related AIAs discussed include pulse agglutination reactions and bioaffinity or displacement assays. PMID- 2222798 TI - Muscle growth and exercise. AB - This paper first reviews muscle growth and then considers the influence of exercise in growth. Knowledge about how muscle cells grow and some factors that may influence the growth pattern are discussed first since these effects must be considered before the influence of exercise becomes clear. Growth of muscle can occur in three ways: (1) by an increase in muscle cell numbers, (2) by an increase in muscle fiber diameter, and (3) by an increase in fiber length. All three of these mechanisms are involved in muscle growth. However, growth in cell numbers is limited to the prenatal and immediately postnatal period, with the animals and man being born with or soon reaching their full complement of muscle cells. Thus, growth occurs by either hypertrophy of the existing muscle fibers by adding additional myofibrils to increase the muscle mass or by adding new sarcomeres to the ends of the existing muscle fibers to increase their length. Both of these mechanisms occur during the growth process. Growth in the girth of the muscle fibers appears to take place by splitting of the myofibrils. This may be stimulated by development of stress creating an unequal pressure with splitting at the Z-band and development of additional SR and T-tubule systems. This adds to the diameter or girth of myofibers without any hyperplasia. The growth in length occurs at either end of the fibers and results in addition of new sarcomeres. In both cases, new myofibrillar protein must be synthesized and deposited in the muscle cells. It is suggested that adaptation by adding or removing sarcomeres is physiologically determined by the degree of force a muscle can generate that is in turn dependent on the degree of overlap of the thick and thin filaments. Thus, the amount of tension would control the number of in-series sarcomeres in a single muscle fiber. Nutrition is also known to play an important role in muscle and was discussed from the standpoint of the effects of nutritional adequacy and restriction. Although a nutritionally balanced and calorically adequate diet is required to achieve optimum muscle growth, it may be less efficient in terms of protein deposition than a moderately restricted diet. Muscle and bone deposition, however, can be limited on severely restricting the dietary intake. Although fat deposition is the first tissue to suffer on a severely restricted diet, muscle and bone follow next with the nervous system, brain and eyes being the last systems to be affected.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2222797 TI - Integrity of small data bases in computer analysis of dietary data. AB - The integrity of data bases to support microcomputer-based dietary analysis programs has become increasingly important to developers and users of nutritional analysis software. This paper reviews critical issues in maintaining data integrity during development of small nutritional data bases. Because a limited number of large, source data bases provides the data for smaller, special-purpose data bases, this review initially focuses on factors that affect the quality and precision of methodologies used in establishing large data bases. Issues discussed are accuracy of source data as determined by analytical methodology and imputation procedures, and methods for insuring representativeness of data. The effect of data transfer procedures on small data base integrity are discussed, including use of multiple sources and standardization of naming and coding conventions. Also reviewed are procedures for selecting reduced numbers of foods and nutrients without sacrificing accuracy of analysis, and methods currently in use for validating small data bases. PMID- 2222799 TI - Influence of dietary magnesium on mineral, ascorbic acid and glutathione concentrations in tissues of a freshwater fish, the common carp. AB - Supplementation with dietary Mg at a minimum level of 0.06% seems to be essential to prevent the hypercalcinosis of the kidney and hepatopancreas in a fish, the common carp. Mg deficiency appears to have no effect on the Mg level in kidneys and hepatic tissue, whereas the Fe level in those tissues was significantly diminished by increasing dietary Mg supplementation up to 3.2 g.kg-1. Both hypercalcinosis and accumulation of Fe in soft tissues were more pronounced in fish offered diets high in protein (44%) compared to fish on low dietary protein (25%). The ascorbic acid in the hepatopancreas and kidney was greatly depleted in fish fed the high-protein diets, and this depletion did not correlate with the dietary Mg level nor with a high level of tissue Ca. However, the increased Ca concentration in the kidney coincided with the greatest depletion of ascorbate in fish fed a high-protein diet. The concentration of ascorbate in the brain was much less affected by a low level of vitamin C in the diets than in other tissues. Depletion of ascorbate in soft tissues did not correspond to fish growth but might be rather related to the metabolic rate imposed by the dietary nutrients. It is suggested that the Mg and ascorbic acid requirements in the carp are considerably elevated by the increased dietary protein level. PMID- 2222800 TI - Severe hypermagnesemia without reduction in the anion gap. AB - The serum anion gap (AG) is usually calculated by the equation: AG = Na - (Cl + HCO3), reflecting the difference between the total level of unmeasured anions (all anions other than chloride and bicarbonate) and that of unmeasured cations (all cations other than sodium). Thus, several recent reviews have cited hypermagnesemia as a cause of a reduction in the AG. Whether this might occur depends in part on the nature of the accompanying anion (if the etiology of the hypermagnesemia is an exogenous load of magnesium), as well as on the presence of concomitant changes in endogenous unmeasured anions. In the present paper, we describe an unusual patient whose severe hypermagnesemia was not associated with AG reduction. Although multiple factors, including lactic acidosis, might have countervailed the effect of her hypermagnesemia on the AG, there is no actual substantiation in the literature of an association between increased serum Mg and AG lowering. In conclusion, the finding of a normal AG has no documented negative predictive value, and the finding of a low AG has no documented positive predictive value for the diagnosis of hypermagnesemia. PMID- 2222801 TI - Studies on the relationship between boron and magnesium which possibly affects the formation and maintenance of bones. AB - Recent findings are reviewed indicating that changes in dietary boron and magnesium affect calcium, and thus bone, metabolism in animals and humans. In animals, the need for boron was found to be enhanced when they needed to respond to a nutritional stress which adversely affected calcium metabolism, including magnesium deficiency. A combined deficiency of boron and magnesium caused detrimental changes in the bones of animals. However, boron deprivation did not seem to enhance the requirement for magnesium. In two human studies, boron deprivation caused changes in variables associated with calcium metabolism in a manner that could be construed as being detrimental to bone formation and maintenance; these changes apparently were enhanced by low dietary magnesium. Changes caused by boron deprivation included depressed plasma ionized calcium and calcitonin as well as elevated plasma total calcium and urinary excretion of calcium. In one human study, magnesium deprivation depressed plasma ionized calcium and cholesterol. Because boron and/or magnesium deprivation causes changes similar to those seen in women with postmenopausal osteoporosis, these elements are apparently needed for optimal calcium metabolism and are thus needed to prevent the excessive bone loss which often occurs in postmenopausal women and older men. PMID- 2222802 TI - Effects of vasoactive agents on isolated human umbilical veins in preeclamptic women. AB - Increased peripheral vascular reactivity has been noted in preeclampsia. However, in a recent study we found decreased reactivity to vasoactive agents in umbilical arteries of preeclamptic patients. A similar preliminary study, therefore, was carried out on umbilical veins to determine whether preeclampsia affected umbilical venous reactivity. Helical strips of human umbilical veins from 7 preeclamptic and 8 control patients were set up isometrically in physiological salt solution. The resting tensions did not differ between the groups, but spontaneous rhythmic contractions began much earlier in the preeclamptic group than in the controls (8.29 +/- 4.14 vs. 49.22 +/- 9.71 min). There were no differences in the mean amplitudes of the contractions at their time of onset, but in 5 patients of each group the mean amplitudes progressively rose to a maximum at approximately 90 min after incubation, and this maximum was significantly lower in the preeclamptic group (234.43 +/- 72.95 vs. 751.64 +/- 186.13 mg). The frequencies of the contractions did not vary with time or between groups. Log-dose response curves were made for serotonin and KCl, and there were no differences in threshold doses, ED50, maximal tensions or relaxation times between groups. These results are similar to those reported in human umbilical arteries from preeclamptic patients in that no increase in reactivity to vasoactive agents was noted. In conclusion, the differences in the spontaneous rhythmic contractions between preeclamptic patients and controls may be new evidence of pathological changes in the umbilical venous system in preeclampsia. PMID- 2222803 TI - Extracellular magnesium and potassium concentrations interact to modulate tone and reactivity of isolated canine cerebral vascular muscle. AB - In vitro studies were undertaken to investigate the effects of external potassium [K+]o, 0-7.1 mM, and magnesium [Mg2+]o, 0-4.8 mM, concentration on canine middle cerebral and basilar arterial basal tone and on 5-hydroxytryptamine (5-HT) induced contractions. The lower the [K+]o, the greater the degree of spontaneous contraction upon acute withdrawal of [Mg2+]o. An inverse linear relationship between the concentration of [K+]o and the degree of cerebrovasospasm upon acute withdrawal of [Mg2+]o was observed over the range of 1-6 mM [K+]o. As [K+]o was increased, stepwise, the slow phase of the contractions became attenuated, while the magnitude of the fast phase became progressively smaller. Acute withdrawal of [K+]o produced contraction of middle cerebral and basilar arteries which could be modulated by the concentration of [Mg2+]o. The higher the [Mg2+]o, the less the tension developed upon acute withdrawal of [K+]o. Contractility to 5-HT was depressed when [K+]o was lowered. This attenuation was reversed completely when [Mg2+]o was acutely withdrawn. Sensitivity (EC50) of canine middle cerebral and basilar arteries to 5-HT was inversely related to the [K+]o/[Mg2+]o ratio. These actions took place over pathophysiological ranges of [K+]o and [Mg2+]o. Maintenance of a constant [K+]o/[Mg2+]o ratio, irrespective of the exact [K+]o and [Mg2+]o, produced similar degrees of maximum tension and sensitivity (EC50) to 5-HT. Use of intact ring preparations and helically cut vascular strips produced similar results with varying [K+]o/[Mg2+]o. A variety of pharmacological receptor antagonists (phentolamine, propranolol, atropine, diphenhydramine, cimetidine), as well as a prostaglandin cyclo-oxygenase inhibitor, did not modify the altered contractile responses or basal tone evoked by varying the [K+]o/[Mg2+]o ratios. These experiments suggest: (1) that basal tone and contractility of canine cerebral vascular smooth muscle cells appear to be exquisitely sensitive to alterations in extracellular K+ and Mg2+ and (2) that 5 HT receptor-operated Ca2+ channels, as well as those Ca2+ channels involved in the generation of cerebral arterial basal tone, are modulated and controlled by the precise concentrations of [K+]o and [Mg2+]o. PMID- 2222804 TI - Relationship between diabetes mellitus mortality rates and drinking water magnesium levels in Iowa. AB - A recent ecologic study has suggested a relationship between mortality from diabetes mellitus and levels of magnesium in drinking water. However, diabetes mortality rates were from aggregate data for the entire geographic area under study. The state of Iowa has data resources available to determine diabetes mortality rates for individuals on known water supplies in Iowa and magnesium levels for raw drinking water supplies. To determine the presence of this relationship in the state of Iowa, mortality rates from 1976 through 1985 for diabetes as an underlying cause of death and for major cardiovascular disease with diabetes as an ancillary cause of death were compared for individuals from towns in Iowa with populations of 1,000 to 10,000. At the stratification levels of magnesium in municipal drinking water used in this study, no significant differences were found in diabetes mortality rates. PMID- 2222805 TI - Measurement of ATP synthesis and flocculent matrix densities in mitochondria as a function of 'in vitro' ischemia in the heart and liver of rats. AB - We intended to determine the levels of adenosine triphosphate (ATP) synthesis at the time when mitochondria ultrastructurally show flocculent densities in the matrix space. For this purpose, mitochondria were isolated from rat heart and rat liver after the tissues have been maintained under controlled ischemic conditions in vitro at 37 degrees C for intervals of 15, 30, 45, 60, 120, 180, and 240 (heart) min. The isolated mitochondria were tested for new ATP synthesis by luciferin/luciferase luminescence in the presence of substrate and adenosine 5' diphosphate (ADP). The luminescence peaks were standardized and related to an external measure by measuring absorbance of ATP at 259 nm where the extinction coefficient is 15,400. Mitochondrial yield was monitored by measuring succinate dehydrogenase activity in the first homogenate and in the final mitochondrial pellet. Alternatively, cytochrome oxidase activity was used and the protein in the mitochondrial pellet was also determined. We found that the yield of mitochondria was above 53-54% in both liver and heart at 2 h of ischemia. Longer intervals were accompanied by lower yields. The ability to synthesize new ATP declined at different time intervals in ischemia of the heart compared to the liver. After 30 min ischemia, the synthesis in heart mitochondria is 18% of control, while the synthesis of liver mitochondria reaches 16% of control after 45 min of in vitro ischemia. Flocculent densities in heart mitochondria appeared at 45 min ischemia in vitro and in vivo, and at 60 min in liver mitochondria. We conclude that the decline of ATP synthesis is a significant early change in mitochondria and antedates the appearance of flocculent densities. PMID- 2222806 TI - Postmortem viability and early changes in organ culture of human and rabbit aortic endothelial cells. AB - In order to understand the role of the postmortem interval (PMI) on endothelial cell changes both in human and rabbit aortas, we have examined the ultrastructural cytomorphologic alterations of these cells. Human aorta (HA) and rabbit aorta (RA) were maintained in calcium-free, glucose-supplemented Hank's balanced salt solution (HBSS). Rabbit endothelial cells (REC) on the aorta (organ culture) assayed morphologically survive for at least 12 h in culture solution. The predominant morphological change in the RA was the formation of multiple subendothelial vacuoles (SEV). These vacuoles may form as the results of increased permeability of endothelial cells to ions and fluid or cell contraction. Cell to cell connection remained intact. Individual and dispersed endothelial cells were observed 8 h after removal from the animal when incubated in calcium-free HBSS. These necrotic endothelial cells were scattered among viable endothelial cells. Human aortic endothelial cells were also well preserved in the same media for periods of 6-8 h postmortem. Increased extracellular calcium (1.3 mM) in the incubation media caused accelerated cell death. These findings suggest that aortic endothelial cells can be preserved for longer periods of postmortem time than would be expected and that the use of calcium free HBSS media supplemented with glucose improves endothelial cell viability in vitro. PMID- 2222807 TI - Oncogene activation and hepatocarcinogenesis. AB - Dominant-transforming oncogenes are frequently detected in mouse liver tumors, but are rare or inconsistently detected in rat liver tumors. Most of those that have been identified are members of the ras family. While altered expression of many oncogenes has been reported, an increase in the expression of the c-myc gene is consistently observed in both rat and mouse hepatocellular tumors. Both hepatocytes and liver epithelial cells have been immortalized or transformed with viral or cellular oncogenes. Immortalization of cells occurs without the loss of differentiated functions, while transformation induces the expression of many genes/gene products associated with liver cancer in vivo. Cells transformed with chemical carcinogens or oncogenes display a phenotype of growth factor independence or greatly reduced growth factor requirements. Transformation is frequently associated with a substantial decrease in the expression of the exogenous growth factor receptor in the hepatocellular tumors. PMID- 2222808 TI - Differing roles of protein kinase C on the antiproliferative effects of tumor necrosis factor alpha and beta on LoVo cells. AB - In this study we examined whether the antiproliferative effects of tumor necrosis factor (TNF)-alpha and beta were associated with the activation of protein kinase C (PKC), using the LoVo human colon cancer cell line which is resistant to both TNFs. In combination with 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of PKC, TNF-alpha caused marked growth inhibition of LoVo cells, but TNF-beta had little antiproliferative effect. There was no difference in the effect when TPA was added 1 h before or 4 h after TNF-alpha administration. A PKC inhibitor, H-7, not only decreased the sensitivity of LoVo cells to TNF-alpha but also caused a slight promotion of cell proliferation and dose-dependently blocked the growth inhibition induced by TNF-alpha and TPA. These results suggested a possible regulatory function of PKC within the TNF-alpha-mediated intracellular signalling pathway. PKC may act at a later stage in the transduction pathway. PMID- 2222809 TI - Measurement of homing receptors on the surface of leukemic and nonleukemic cell lines. AB - Selective homing of hemopoietic progenitor cells to hemopoietic organs is the initial event in hemopoiesis. At a molecular level, it is mediated by a membrane receptor on the surface of hemopoietic progenitor cells. The receptor molecule then binds selectively to a glycoconjugate on the surface of bone marrow stromal cells. The molecular nature of this receptor has been shown previously to be a lectin with specificity for an as yet unknown configuration of galactosyl and mannosyl residues of the glycoconjugate. Normal murine progenitor cell lines, FDCP-1 and B6SUT, were found to possess this homing receptor on their cell membrane, and they also bind well to hemopoietic stroma. However, when three human leukemic cell lines, U937, HL60 and K562, were probed for the presence of this receptor, they were found to be deficient in the homing protein. Further, these cells showed little ability to bind the hemopoietic stromal cell line, GB1/6. These findings suggest that leukemic cells experience a loss, or at least alteration, of homing receptor molecule during leukemic transformation. This can result in a diminished ability to bind to marrow stroma. The lack of homing function may be of pathogenetic significance in the lack of differentiation of leukemic cells and may also contribute to the dissemination of leukemic cells in the circulation. PMID- 2222810 TI - Characterization of the cDNA coding for mouse prothrombin and localization of the gene on mouse chromosome 2. AB - A series of overlapping cDNAs coding for mouse prothrombin (coagulation factor II) have been isolated and the composite DNA sequence has been determined. The complete prothrombin cDNA is 1,987 bp in length [excluding the poly(A) tail] and codes for 18 bp of 5' untranslated sequence, an open reading frame coding for 618 amino acids, a stop codon, and a 3' untranslated region of 112 bp followed by a poly(A) tail. The translated amino acid sequence predicts a molecular weight of 66,087, which includes 10 residues of gamma-carboxyglutamic acid. There are five potential N-linked glycosylation sites. Mouse prothrombin is 81.4% and 77.3% identical to the human and bovine proteins, respectively. Comparison of the cDNA coding for mouse prothrombin to the human and bovine cDNAs indicates 79.9% and 76.5% identity, respectively. Amino acid residues important for the structure and function of human prothrombin are conserved in the mouse and bovine proteins. In the adult mouse and rat, prothrombin is primarily synthesized in the liver, where is constitutes 0.07% of total mRNA as determined by solution hybridization analysis. The genetic locus for mouse prothrombin, Cf-2, has been mapped using an interspecies backcross and DNA fragment differences between the two species. The prothrombin locus lies on mouse chromosome 2, 1.8 +/- 1.3 map units proximal to the catalase locus. The gene order in this region is Cen-Acra-Cf-2-Cas-1-A-Tel. This localization extends the proximal boundary of the known region of homology between mouse chromosome 2 and human chromosome 11p from Cas-1 about 2 map units toward the centromere. PMID- 2222811 TI - Molecular cloning of cDNAs encoding bovine and human lactoperoxidase. AB - Peptide sequences obtained from cyanogen bromide fragments of bovine lactoperoxidase (bLPO) were used to design oligonucleotide probes for library screening. These probes were used to screen a cDNA library constructed from bovine mammary tissue. Three overlapping clones were obtained, the longest of which (T3) contained a reading frame of 712 amino acid residues. The encoded amino acid sequence was homologous to those recently reported for myelo-, thyro-, and eosinophil peroxidases. Two possible amino termini of the mature enzyme were identified, and the predicted mature protein matched previous molecular weight estimates of 78,500. Of eight bovine tissues tested, transcription of T3 sequences were detected in mammary tissue only. Using the bLPO cDNA as a probe, a single hybridizing clone was found in a human mammary gland cDNA library. This clone (M1) encoded the carboxy-terminal 324 residues of a peroxidase distinct from the other three known human peroxidases, and was closely related to bLPO. This result confirms the presence of at least one distinct lactoperoxidase in humans. PMID- 2222812 TI - Tissue-specific expression of the rat growth hormone gene is due to the interaction of multiple promoter, not enhancer, elements. AB - Expression of the rat growth hormone (rGH) gene is highly tissue-specific, being limited to a subset of cells in the anterior pituitary. DNA sequences within 237 bp of the transcription start site of the rGH gene play a major role in directing the expression of this gene in the pituitary. Transfection studies in cultured rat pituitary (GC) cells demonstrate that optimal expression of rGH requires the binding of at least two non-tissue-specific factors whose contribution to rGH expression is dependent on the binding of the pituitary-specific factor, Pit-1. Although the segment of DNA containing the elements to which these factors bind can direct pituitary-specific expression of a gene lacking upstream promoter elements, it cannot confer stimulation to either a heterologous or homologous promoter when placed downstream from the coding sequences. These results suggest that expression of the rGH gene exclusively in the pituitary is due to the activity of a tissue-specific promoter element, not an enhancer. PMID- 2222813 TI - Reliable hybridization of oligonucleotides as short as six nucleotides. AB - Although there are many new applications for hybridizing short, synthetic oligonucleotide probes to DNA, such applications have not included determining unknown sequences of DNA. The lack of clear discrimination in hybridization of oligo probes shorter than 11 nucleotides and the lack of a theoretical understanding of factors influencing hybridization of short oligos have hampered the development of their use. We have found conditions for reliable hybridization of oligonucleotides as short as seven nucleotides to cloned DNA or to oligonucleotides attached to filters. Low-temperature hybridization and washing conditions, in contrast to the high stringency conditions currently used in hybridization experiments, have the potential for allowing the simple use of all oligos of six nucleotides or longer in meaningful hybridizations. We also present the hybridization discrimination theory that provides the conceptual framework for understanding these results. PMID- 2222814 TI - Transcription vectors that facilitate the identification and mapping of RNA splice sites in genomic DNA. AB - Two transcription vectors were constructed that can identify the splice sites at exon-intron boundaries of inserted DNA fragments possessing the complementary splice site. One vector contains the 5' splice donor site and flanking exon intron sequences from the 3' end of the adenovirus first late leader. The other vector contains the 3' splice acceptor site and the branch acceptor site, plus the flanking exon-intron sequences from the 5' end of the adenovirus second late leader. Both vectors contain a multiple cloning site for insertion of DNA fragments. DNA fragments supplying the complementary splice site, including the adjacent exon and intron sequences, were inserted into the vectors. The vectors were used as templates for the synthesis of chimeric RNA transcripts that were spliced in in vitro splicing extracts. Chimeric transcripts from the vectors containing complementary splice site boundary regions from the human growth hormone gene were accurately spliced in vitro. A splice site from a human growth hormone intron that is not normally spliced in vitro was spliced when paired with an adenovirus splice site. These vectors can be used to identify splice sites and to determine the lengths of exons and their attached introns within a DNA fragment of unknown coding content. PMID- 2222815 TI - Legal issues in the practice of dental hygiene. PMID- 2222816 TI - Emergency medicine in dentistry. PMID- 2222817 TI - [Migraine. Various current concepts]. AB - Migraine is a common disorder in children with a prevalence of 2.5% under seven years of age, 5% in those between the ages of seven and puberty and in postpuberal females it may be as prevalent as 10%. It is transmitted as an autosomally dominant trait and is frequently caused by precipitating factors. The vascular theory which stated that the aura was due to an intracranial vessel constriction and that the headache was due to an extracranial vasodilation has now be questioned due to new clinical and experimental data. Recently it is believed to be due to an unstable inherited serotonigenic neurotransmission which favors an increase in the frequency of neuronal discharge of the mid-brain raphe. Included is a classification and the diagnostic headache criteria used by the International Headache Society (1988). Treatment for migraine can be: a) abortive and b) preventive. Propranolol at a dosage of 2 mg/kg per day taken divided into three has shown to be the most beneficial in the prevention of migraine headaches. Certain calcium channel blockers, particularly flunarizine seem to have prophylactic value. PMID- 2222818 TI - [Results of the treatment of growth hormone deficiency with methionine somatotropin or recombinant somatotropin]. AB - Sixteen children with hGH deficiency were treated for a year with methionyl somatotropin (Somatonorm) or recombinant-somatotropin (Genotropin). The hormone was administrated subcutaneously 3 time/week, 0.45-0.6 IU/kg/week. After a year of treatment, the mean growth rate in those who received Somatonorm increased from 3.96 +/- 0.8 cm/yr to 9.08 +/- 2.7 cm/yr, and in those who received Genotropin from 3.6 +/- 0.6 cm/yr to 8.58 +/- 1.1 cm/yr with no significant difference. No adverse effects were observed, but four children that received Somatonorm developed antihGH antibodies with a very low binding capacity, of less than 0.1 mg/L. All the children that received Genotropin were negative for antihGH antibodies. PMID- 2222819 TI - [Increase in glutamic-oxaloacetic and glutamic-pyruvic transaminases and lactic dehydrogenase as a diagnostic aid in perinatal asphyxia]. AB - In order to determine the behavior of glutamic oxalacetic (GOT), glutamic-pyruvic (GPT) and lactic dehydrogenase (LDH) transaminases after a period of asphyxia, a study was conducted in 120 newborn children which were placed into two groups: group 1 of the asphyxiated children who were given oxygen at intermittent positive pressure for more than a minute and group 2 of healthy children with an Apgar greater than 7 after the first and five minutes and without any apparent pathology. The results showed a real increase in the quantities of all three transaminases among those in the group of asphyxiated children, which on the other hand did not occur in the healthy group of children where levels remained normal. There was statistical differences (P less than 0.001) by which we can conclude that the quantification of these enzymes can be useful as a diagnostic tool in cases of perinatal asphyxia. PMID- 2222820 TI - [Uncinariasis in younger infants]. AB - In order to determine the main clinical and laboratory manifestations associated with the infestation by an uncinaria during the first year of life, 42 children were studied from a group hospitalized between the years 1980 and 1985 in whom the main diagnosis at their time of leave from the hospital was parasitosis. Over 31 patients (74%) showed some degree of malnutrition, and severe in 24 of them (57% of the total). Clinical manifestations were mainly related to anemia (paleness, lack of air) and active intestinal bleeding (enterorrhagia, melena). Among the laboratory findings, 80% of the patients were shown to have anemia and in 24% of them, their hemoglobin levels were less than 5 g/dL, in more than half the anemia was normocytic normochromic. Also included are particularities concerning uncinariasis in the breast-feeding infant and some differences with the infection in the adult. PMID- 2222821 TI - [Measurement of the choroid plexus of the lateral ventricles in full-term newborns using ultrasonics]. AB - Brain ultrasonography was carried out in 50 full-term, healthy newborns in order to obtain normal measurements of the choroid plexus of the lateral ventricles to have a basis to work with in future studies concerning Central Nervous System infections where the choroid plexus may be affected early on due to the bacterial infection. The parasagittal views demonstrated the anterior-posterior diameter of the left choroid was on the average 0.52 cm and 0.50 cm for the right one. The posterior coronal view showed the length of the left choroid plexus to be on the average 2.29 cm and 2.34 cm for the right. The transverse diameter as seen from a coronal view was 0.55 cm for the left choroid and on the average 0.52 for the right. PMID- 2222822 TI - [Hearing and language sequelae in survivors of a neonatal intensive care unit]. AB - INTRODUCTION: The purpose of this study is to record the hearing and language sequelae in a sample of children from the Intensive Care Unit between the ages of two and three. MATERIALS AND METHODS: Forty-one children were studied after being submitted to neuropsychological, hearing and language tests. Both normal and abnormal parameters for each test allowed the categorization of the children. RESULTS: In the general sample there were 24 full-term children versus 17 preterm children. The neurological testing showed a tendency towards normality. The same was seen in language testing since the proportion of normality corresponded to those children born after a full term. There were practically no differences in those suspected from both groups and a greater percentage of abnormal children were found among the pre-term infants. From an audiological standpoint there was a predominance of normal children; there was only one patient with severe bilateral hypoacusis who needed an electric auxiliary hearing device and two other patients with peripheral ear dysfunction classified as serous middle ear otitis. CONCLUSIONS: The incidence of hypoacusis in this sampling type is similar to that reported in the literature. Those patients with a history of assisted mechanical ventilation have been later found to have, as a sequelae, serous middle ear otitis, which corresponds to that reported by Paradise. The development of language stages were altered more so in preterm children. In some patients, the lack of stimulation associated with a low socioeconomic back group favors the delay in the development of language skills. PMID- 2222823 TI - [Management of primary nocturnal enuresis in school children with slow learning ability: usefulness of imipramine]. AB - A comparative, longitudinal, blind prospective study was carried out in 20 students between the ages of 6 and sixteen with primary nocturnal bedwetting and slow learning abilities from the Fray Antonio Alcalde school, in order to evaluate the use of motivating reinforcement techniques, exercises in order to improve bladder function and treatment with imipramine. All of the patients were given motivation reinforcement and bladder exercises. They were later divided into two groups of 10 children; group A was given a placebo while group B was given imipramine. In group A a significant decrease was seen in the average number of days the children woke wet after the sixth month of treatment (13.2 +/- 9.7 days to 3.7 +/- 7.15 days) with P less than 0.05; and in group B since the fourth month (16.6 +/- 7.8 days to 8.1 +/- 8.3 days) with a P less than 0.05. At the end of the study, seven patients from group A and five patients from group B decreased in over 80% the number of days which they woke up wet. The motivating reinforcement and the exercises used to improve bladder functional capacity are useful in the management of primary nocturnal enuresis. Imipramine, when combined with these other routines can shorten the time towards a favorable response. PMID- 2222824 TI - [Acute trichinosis in children. Intrafamilial epidemic outbreak in Mexico City]. AB - Four cases of trichinosis found in a family living in Iztapalapa, Mexico, D.F. are reported. The family reported to frequently eat raw sausage originally from Villanueva, Zacatecas from which Trichinella spiralis larvae were isolated. Diagnosis was difficult in the first case since no epidemiological history was associated with the patient, besides the fact that the patient showed no signs of eosinophilia and blood tests were negative. The diagnosis in this case was confirmed through muscular biopsy. The predominating symptomatology consisted in the trilogy of fever, eyelid edema and myalgias. PMID- 2222825 TI - [Adrenal abscess in the newborn: a case report and review of the literature]. AB - This is a case report concerning a 22 day newborn referred to us having an abdominal tumor, fever, an irritable nature and feeding refusal, born dystocically due to the retention of the shoulders and having an Apgar score of 5/8. When admitted the presence of the tumor was corroborated in the right flank occupying the right renal fossa and measuring 5 x 8 cm, non-mobile and painless. Studies revealed a diagnosis of calcified right adrenal hemorrhage versus neuroblastoma. During surgery a right adrenal abscess was found which was drained and a biopsy sample was taken for further study. The culture of the pus developed Proteus mirabilis. Pathology reported it to be an abscessed right adrenal hematoma which was partially calcified. The patient's wound became infected but was later sent home under good conditions. Only 15 other cases with this pathology are reported in the literature, this would be the 16th case. An emphasis is placed on including this pathology as part of the differential diagnosis of retroperitoneal tumors in the newborn. PMID- 2222826 TI - [Water-electrolyte and acid-base disorders. VII. Metabolic alkalosis]. AB - Metabolic alkalosis is defined as a primary increase in plasma bicarbonate concentration. As a consequence of this increase, systemic alkalemia and secondary hypercapnia develop. In most instances metabolic alkalosis arises from loss of acid through the kidney or gastrointestinal tract. The causes of metabolic alkalosis can be separated into two groups. Those forms of alkalosis responsive to chloride salt administration (e.g., vomiting), are associated with extracellular fluid volume and chloride depletion. In contrast, alkalosis resistant to administration of chloride salt (e.g., primary aldosteronism), is usually associated with extracellular fluid volume expansion and a urine chloride above 20 mEq/L (mmol/L). Metabolic alkalosis; causes; diagnosis; clinical manifestations. PMID- 2222828 TI - [Treatment of hyperkalemia using salbutamol]. PMID- 2222827 TI - [Infantile-type adrenoleukodystrophy]. PMID- 2222830 TI - Viral vaccines. PMID- 2222829 TI - [Abstracts of papers presented at the XXXV annual meeting of the Medical Association of the Federico Gomez Childrens Hospital of Mexico, November 1989. Morelia, Michoacan]. PMID- 2222831 TI - Serum albumin beads possessing slow-release properties for vaccines. PMID- 2222832 TI - Use of combined viral vaccines. PMID- 2222833 TI - Vaccination against influenza viruses: current status. PMID- 2222834 TI - Cold-adapted influenza viruses for use as live vaccines for man. PMID- 2222835 TI - Vaccines against viruses associated with diseases in human central nervous system. PMID- 2222836 TI - Rabies vaccines from Pasteur's time up to experimental subunit vaccines today. PMID- 2222837 TI - World Health Organization attitude concerning the use of continuous cell lines as substrates for production of human virus vaccines. PMID- 2222838 TI - Subunit vaccines against infection by enveloped viruses. PMID- 2222839 TI - Baculovirus expression vector system for production of viral vaccines. PMID- 2222840 TI - Ethanol effects in an anxiety/defense test battery. AB - Two tests, components of an Anxiety/Defense Test Battery, have been designed to measure risk assessment, inhibition of nondefensive behaviors, and movement arrest, all of which occur in the natural defense patterns of rats to threatening stimuli. In these tests, which used a nonpainful threat stimulus (a cat), ethanol (0.6 and 1.2 g/kg) increased two risk assessment behaviors on an initial test day, and produced a wider pattern of changes in all three patterns on a retest (no cat) day, 5 days later. The pattern of results obtained is compatible with a view that defensive behaviors occur in a fixed sequence with the decreasing intensity of threat an important factor in the transition from one defensive behavior to the next, and with ethanol at these doses producing a mild and relatively nonspecific anxiolytic effect. Comparison of male and female subjects on these tasks also suggested that females are more defensive than males, a finding which agrees with a variety of human anxiety studies but is at variance with previous rodent literature. PMID- 2222841 TI - Interactive effects of ethanol intake and maternal nutritional status on skeletal development of fetal rats. AB - Skeletal development on gestation day 21 was examined in fetuses of alcohol consuming (A), pair-fed (PF) and ad lib-fed (C) Sprague-Dawley females. Ethanol (36% ethanol-derived calories) was administered in liquid diets that were marginal (Diet A1) or optimal (Diet A2) in terms of pregnancy requirements (18% vs. 25% total calories as protein, respectively). For each bone studied, a lengthwise measurement was made of the whole bone and of the ossified portion(s), and percent ossification was calculated. Number of sternebral ossification centers present was also determined. Alcohol-exposed fetuses showed retarded ossification of the tibia and radius, regardless of maternal protein intake. Increasing the protein content of the alcohol diet from 18% (Diet A1) to 25% (Diet A2) significantly increased ossification of the ulna, sternum, humerus and ilium-ischium. For the ulna, A2 fetuses showed greater ossification than A1 fetuses but were still retarded compared to PF and C fetuses. For the sternum, humerus and ilium-ischium, however, ossification in A2 fetuses increased to the levels observed in the PF and C groups. In addition, number of sternebral ossification centers present was significantly increased in A2 compared to A1 fetuses. These data indicate that skeletal development provides a sensitive index of ethanol-induced developmental delay as well as interactive effects of ethanol and nutrition. PMID- 2222842 TI - Methodological aspects of aldehyde dehydrogenase assay by spectrophotometric technique. AB - Aldehyde dehydrogenase (ALDH) activity was assayed spectrophotometrically by measuring the increase in delta A at 340 nm, as a criteria of NAD conversion to NADH in the presence of propionaldehyde. The effect of pH and substrate(s) concentration of nonenzymatic increase in absorbance at 340 nm was studied. Results indicate that the increase in absorbance at 340 nm is not entirely due to NAD conversion to NADH. It was observed that nonenzymatic interaction of NAD and aldehyde could as well result in increase in absorbance at 340 nm. The magnitude of the nonenzymatic contribution towards increase in absorbance at 340 nm is found to be pH, substrate(s) conc., and time dependent. Further, the observed nonenzymatic reaction product was found to be different from that of NADH as confirmed by u.v. spectral characteristics (lambda max. 346 nm) and its inability to activate NADH/NADPH-dependent glutathione reductase. Based on these findings, a final assay method comprising a substrate blank consisting of NAD and aldehyde, and the assay pH of 7.4 is recommended for measuring the ALDH activity. Further, under these experimental conditions the Km value of human RBC ALDH was found to be 0.59 mM for propionaldehyde substrate. PMID- 2222843 TI - Plasma beta-endorphin levels in chronic alcoholics. AB - In order to test the possible relationship between the chronic consumption of alcohol and the opioid system, we have measured the plasma levels of beta endorphin in a group of 31 alcoholic patients and compared the results with those of a control group of 16 subjects. Our results show that chronic consumption of alcohol induces a significant decrease in beta-endorphin (beta-end) plasma levels regardless of either the disease suffered by the alcoholic patient or of the time of abstinence studied (one month maximum). Thus we believe that the beta-end decrease may well be due to the patients' alcoholism and that it might be mediated by the tetrahydroisoquinoline system, or be a cause of alcoholism rather than a consequence. PMID- 2222844 TI - Effect of acute ethanol drinking on alcohol metabolism in subjects with different ADH and ALDH genotypes. AB - The effect of different amounts of orally ingested ethanol on plasma alcohol dehydrogenase (ADH) and erythrocyte aldehyde dehydrogenase (ALDH), as well as on the blood ethanol and acetaldehyde levels, was examined in healthy nonalcoholic subjects. The genotypes at ADH2 and ALDH2 locus were identified in enzymatically amplified blood DNA by hybridization with allele-specific oligonucleotides. While the Japanese subject was found to be genotypically heterozygous for both ADH2 and ALDH2, the Caucasian subjects were genotypically homozygous normal for these alleles. A faster ethanol elimination associated with a higher blood acetaldehyde level was observed in the Japanese subject as compared to Caucasian subjects. However, no significant change in ADH and ALDH enzyme activities was detected as the result of acute ethanol intake. PMID- 2222845 TI - Effect of ethanol on the morphohistogenesis and differentiation of cerebellar granule cells in the chick embryo. AB - In this present study we analyse, with the help of the Golgi method, the effect of ethanol on the morphological differentiation of the cerebellar granule cells in the chick embryo. Ethanol seems to affect the process of cell migration from the early stages of differentiation. Some granule cells appear to differentiate in an inverted position. These observations also confirm, on the basis of their axon morphology, the existence of three types of granule cells in the chick cerebellum. PMID- 2222846 TI - Comparison of sensitivity and alcohol consumption in four outbred strains of rats. AB - Differences in alcohol consumption and in sensitivity to the effects of ethanol were investigated in four outbred rat strains: Fischer 344, Long-Evans, Sprague Dawley and Wistar. Alcohol consumption was measured in all four strains in three separate subgroups for each strain, using three different concentrations of ethanol (5, 10 and 20% v/v). An intermittent forced alternate-day ethanol presentation procedure (ethanol as the sole fluid for one day followed by only water the next day), as well as a two-bottle choice paradigm, were employed for this purpose. Ethanol-induced hypothermia and motor impairment (tilting plane test) were used to assess sensitivity. Significant differences in alcohol consumption were found among these strains. The Long-Evans strain consumed the highest and Fischer 344 the lowest amount of ethanol. Wistar and Sprague-Dawley were intermediate. However, the strains did not differ in sensitivity to ethanol. Similarly, determination of sensitivity to ethanol on day 0 in separate groups of these four strains (same age and weight, and obtained at the same time from the same supplier) did not reveal graded differences in sensitivity (hypothermia and motor impairment) corresponding to differences in alcohol consumption. These results suggest that sensitivity does not correlate with alcohol consumption. PMID- 2222847 TI - In vivo proton magnetic resonance spectroscopy of alcohol in human brain. AB - The covariance between blood and brain alcohol levels and subjective reports of mood were examined in 6 healthy adult men after consumption of 0.7 g/kg of beverage alcohol. There was significant (p less than 0.01) temporal concordance between ascending and peak blood alcohol levels and regional brain alcohol levels as measured by in vivo proton Magnetic Resonance Spectroscopy (MRS) when N-acetyl aspartate (N-AA) concentration was used as an internal standard. The frequency of reports of both euphoria and dysphoria also paralleled the ascending limb of the blood and brain alcohol curve. However, peak blood alcohol levels were higher (125.67 +/- 10.91 mg/dl) and earlier (35 min postdrinking) than peak brain alcohol levels (26.25 +/- 6.38 mg/dl) detected 50 min after alcohol intake. This difference in brain and blood alcohol levels appears to be associated with the echo time (TE) parameters of the MRS. A decrease in TE from 270 msec to 50 msec resulted in a marked increase in brain alcohol detectability. MRS measures will permit analysis of regional differences in brain alcohol concentrations and covariance with behavioral, neurophysiologic and neuroendocrine concomitants of acute alcohol intoxication in man. PMID- 2222848 TI - Anatomical "circuitry" in the brain mediating alcohol drinking revealed by THP reactive sites in the limbic system. AB - The involvement of aldehyde adducts in the etiology of alcoholism continues to be supported by a number of experimental findings. These metabolites are synthesized endogenously from a condensation reaction of a biogenic aldehyde with a catechol- or indole-amine and act in the brain to augment or suppress the drinking of ethyl alcohol. When given by the intracerebroventricular route in an animal which does not prefer alcohol, certain tetrahydro-isoquinolines and beta-carbolines can augment significantly the voluntary intake of alcohol even in aversive concentrations. This paper describes the historical background and current status of the "Multiple Metabolite" theory of alcoholism. The recent identification of anatomical structures in the limbic-midbrain, limbic-forebrain of the Sprague Dawley rat, which mediate changes in the intake of alcohol induced by tetrahydropapaveroline (THP) is also described. When injected in a low dose of 25 ng in a specific site, over a 3-day period, THP induces persistent increases in the intake of alcohol even in aversive concentrations. These THP-reactive sites comprise the substantia nigra, reticular formation, medial lemniscus, zona incerta, medial forebrain bundle, nucleus accumbens, olfactory tubercle, lateral septal nucleus, preoptic area, stria terminalis, and rostral hippocampus. A higher dose of 250 ng THP microinjected at homologous loci tends to inhibit the rat's self-selection of alcohol or exert no effect on drinking. Morphological mapping of histologically identified sites sensitive to THP revealed a distinct "circuitry" of neuronal structures overlapping both dopaminergic and enkephalinergic pathways. This "circuit" extends from the tegmental-nigral area of the midbrain rostrally to structures within the limbic-forebrain. When a THP reactive structure, the N. accumbens, was lesioned by either of two neurotoxins, 6-hydroxydopamine or 5.7-dihydroxytryptamine, the rats' preference for alcohol increased sharply. This suggests that impairment of transmitter release, denervation supersensitivity or other perturbation of receptor function within this and other structures play a part in the aberrant drinking of alcohol. It is envisaged that a dopamine-enkephalin link underlies the mechanism for the onset, maintenance and permanency of alcohol preference generated by an aldehyde adduct. Finally, the "Two-Channel, Brain Metabolite" theory of alcoholism proposes that the transitory presence of an endogenously formed aldehyde adduct within cells of the brain causes a permanent perturbation of normal receptor processes and transmitter activity within synapses of specific structures of the limbic system. This theory thus explains the nature of the rewarding properties of alcohol as well as its complex addictive liability which is physiologically irreversible. PMID- 2222849 TI - EEG alpha activity and personality traits. AB - Comparisons between EEG spectral power in the fast alpha (9-12 Hz) range and scores obtained on the Millon Clinical Personality Inventory (MCMI) were made in two populations of subjects. The first was a group of 60 individuals who reported no personal or family history of alcoholism. The second was a subgroup of 13 sons of alcoholics and 13 matched control subjects. In the first population, 30% of the subjects were classified as "high" alpha based on the criteria that their EEG in the 9-12 Hz range was over 75 microV2/octave in amplitude. Using this same criteria, 69% of the sons of alcoholics and 31% of their matched controls were also classified as "high" alpha. In both populations, subjects with high amplitude fast frequency EEG alpha activity in lead P4-O2 scored significantly higher on the Histrionic-Gregarious scale of the MCMI than subjects with low amplitude activity in this lead. These results are consistent with some previous studies showing a positive relationship between EEG alpha activity and extroverted personality traits. These results suggest that fast frequency alpha activity may be associated with some definable personality traits. PMID- 2222850 TI - Event-related potentials in individuals at risk for alcoholism. AB - Visual event-related potentials (ERPs) were recorded to easy and difficult line orientation discriminations in high risk (HR) and low risk (LR) males between the ages of 19-24. The amplitude of the P3 component was significantly smaller in HR compared to LR males to all target stimuli. This result was more pronounced for the easy target. No differences in the latency of P3 were reported between groups. These results were obtained prior to the administration of alcohol and replicate our own findings and those of other laboratories with a different experimental paradigm. PMID- 2222851 TI - Ethanol-induced alterations in EEG alpha activity and apparent source of the auditory P300 evoked response potential. AB - The relationship among topographic brain electrical activity mapping, auditory evoked response potentials (ERPs), plasma ethanol levels and subjective reports of intoxication was examined in 4 male volunteers. The source of the auditory P300 ERP (a measure of selective attention and memory encoding) was estimated using a recently developed computer program. The effect of ethanol on the P300 wave was studied using a standard oddball paradigm both with and without a concomitant divided attention task. Ethanol (0.7 g/kg) administration produced marked increases in EEG alpha activity during the ascending limb of the blood ethanol curve. Acute ethanol administration caused a delay in the latency and a reduction in the amplitude of the auditory P300 ERP. A similar effect on P300 topography was noted in waves that were affected by the tones while the subjects also listened to a story (divided attention). After ethanol, the source of the P300 wave appeared to have shifted to a position posterior and inferior to its original location. P300 ERP's generated during the divided attention task were also disrupted and shifted to positions inferior to their original. However, the variability of the dipole vector was much greater during the divided attention task than after ethanol administration. These data demonstrate that ethanol's effects on cognitive processing skills may be similar to those produced when individuals experience distractions while concentrating on a task. PMID- 2222852 TI - Model estimates of CSF and skull influences on scalp-recorded ERPs. AB - Dipole source localization promises to enhance knowledge about the structural and functional processes underlying differences in scalp-recorded ERPs observed between normal and patient populations. In this paper the Cuffin and Cohen (1) four-compartment model of volume conduction is used to examine the effects of variations in size of different compartments on scalp-recorded potentials. Using single discrete current dipoles located various distances from the center of the head, the effect of varying the thickness of the superficial extra-sulcal subarachnoid layer of CSF and the thickness of the skull are examined. Changing the thickness of the CSF layer alters amplitude recorded at the scalp and also alters the topographic distribution of the potential; these effects are more pronounced the closer the dipole source is to the surface. Changes in skull thickness have similar, but even greater effects. PMID- 2222853 TI - The complete amino-acid sequence and the phylogenetic origin of phycocyanin-645 from the cryptophytan alga Chroomonas sp. AB - The first complete amino-acid sequence of the cryptomonad phycobiliprotein phycocyanin-645 from Chroomonas sp. is presented. The alpha 1-subunit contains 70 amino-acid residues and the alpha 2-subunit 80 residues. In each of the alpha subunits a green, 697-nm absorbing chromophore is covalently bound to Cys18. Both alpha-subunits contain a high number of charged residues. The phycocyanin-645 beta-subunit consists of 177 amino-acid residues. Two phycocyanobilin chromophores are singly bound to Cys beta 82 and Cys beta 158. A purple cryptoviolin-like chromophore is doubly bound to Cys beta 50 and Cys beta 61. Sequence comparisons revealed that the phycocyanin-645 beta-subunit is closely related to red algal phycoerythrin (73% identical amino-acid residues) and not so close to C-phycocyanin (55% identical amino-acid residues). The phycocyanin-645 alpha-subunits represent a special type of phycobiliprotein and a direct relationship to other phycobiliproteins or any light-harvesting polypeptide pigment complexes could not be derived by sequence comparisons. PMID- 2222855 TI - Brefeldin A prevents uncovering but not phosphorylation of the recognition marker in cathepsin D. AB - Brefeldin A (BFA) has been shown to inhibit transiently the subcellular transport of cathepsin D (Oda & Nishimura (1989) Biochem. Biophys. Res. Commun. 163, 220 225). We studied the effect of this antibiotic on processing of the phosphorylated oligosaccharides in cathepsin D in human promonocytes U937. In the presence of the drug the phosphorylation of cathepsin D precursor continued at a diminished rate. The phosphorylated oligosaccharides in cathepsin D comprised mono- and bis-phosphorylated forms. The relative amounts of the two species were not changed in the presence of BFA. The uncovering of the phosphate groups and the proteolytic processing of the phosphorylated precursor were abolished. In an in vitro assay the uncovering enzyme, N-acetylglucosamine-1-phosphodiester N acetylglucosaminidase was not inhibited by BFA. We suggest that this drug interrupts the traffic between the compartments containing N-acetylglucosaminyl phosphotransferase and N-acetylglucosamine-1-phosphodiester N acetylglucosaminidase. PMID- 2222857 TI - Studies on the extraction of different proteoglycan populations in bovine articular cartilage. AB - Large proteoglycan monomers and small dermatan sulfate proteoglycans were extracted from explants of bovine articular cartilage with increasing (0-4 M) concentrations of guanidinium chloride (GuHCl). The first extractions were followed by a second extraction with 4 M GuHCl. The amount of proteoglycans extracted in the first buffer depended on the GuHCl concentration. At low concentrations of GuHCl, a relatively high amount of small proteoglycans was obtained. Fifty percent of the small proteoglycans was extracted in buffer with 0.85 M GuHCl, while 2.0-2.2 M GuHCl was needed to extract half of the large proteoglycans. Immediately after synthesis, 35S-labeled large proteoglycans were extracted much easier (50% at 1.4 M GuHCl), and those extracted at low concentrations of GuHCl were less capable of aggregation with hyaluronic acid. After 7 days of 'chase' these differences between endogenous and 35S-labeled proteoglycans had disappeared. PMID- 2222854 TI - Hemocyanins in spiders, XXIII. Complete amino-acid sequence of subunit a of Eurypelma californicum hemocyanin. AB - The complete amino-acid sequence of subunit a of the hemocyanin of the tarantula Eurypelma californicum was determined by manual sequencing. By limited chymotrypsinolysis, subunit a is split into two fragments of 25 kDa and 40 kDa, respectively, only one single peptide bond being attacked. The whole chain contains 15 methionine residues, after cyanogen bromide cleavage, 15 peptides were identified indicating that one residue (Met85) was not split by the cyanogen bromide reaction. For subcleavages, trypsin, chymotrypsin, Staphylococcus aureus proteinase, and Astacus fluviatilis proteinase were employed. The total chain length comprises 627 amino-acid residues, carbohydrate side chains were not found. PMID- 2222856 TI - Different forms of human cystatin C. AB - Two isoelectric forms of human cystatin C with pI 9.2 and 7.8 have been isolated from urine of patients with different nephrological disorders. Treatment of both forms with alkaline phosphatase revealed that the difference between them is not due to the phosphorylation of some amino-acid residue. Further purification of cystatin C with pI 9.2 by hydrophobic chromatography and N-terminal sequencing showed that it consists predominantly of the full-length form of cystatin C with the N-terminal sequence SSPG-. Cystatin C with pI 7.8 was separated into two peaks. The first represented a pure form truncated by an octapeptide and beginning with the N-terminal sequence LVGG-. The second was a mixture containing 33% of the first peak and 66% of a truncated form with the N-terminal sequence VGGP-. Inhibitory activity of the full-length cystatin C and the pure truncated form has been measured against cathepsins B, H and L and show no significant differences in Ki values. These results further support the proposed mechanism of interaction of cysteine proteinases with their inhibitors cystatins (Bode, W., Engh, R., Musil, D., Thiele, U., Huber, R., Karshikow, A., Brzin, J., Kos, J. & Turk, V. (1988) EMBO J. 7, 2593-2599). PMID- 2222858 TI - Purification and N-terminal amino-acid sequence analysis of rat polymorphonuclear leukocyte cathepsin G. AB - Cathepsin G was purified by single-step cation-exchange chromatography from rat polymorphonuclear leukocytes, obtained from the peritoneal cavity after induction of a mild peritonitis. The 26 N-terminal amino acids were determined and showed 73% identity to those of human cathepsin G. Total amino-acid composition demonstrated a high degree of basic amino acids in accordance with its high affinity for the cationic-exchange gel medium. The protein was found to be a glycoprotein with a glucosamine content of 7.4% of the calculated Mr28,900. On SDS/polyacrylamide-gel electrophoresis the protein showed a Mr of 28,400. It migrated as two bands in a gradient SDS/polyacrylamide-gel indicating isoforms. The pH optimum for the proteinase was determined to be 8.0-8.5 using Suc-Ala-Ala Pro-Phe-Nan as substrate (Suc = 3-carboxypropionyl; Nan = 4-nitroanilide). Km and Kcat/Km values for Suc-Ala-Ala-Pro-Phe-Nan were 0.86mM and 280M-1S-1 and for Suc Phe-Leu-Phe-Nan 0.24mM and 3600M-1S-1, respectively. PMID- 2222859 TI - Purification and characterization of bovine liver 3-cis-2-trans-enoyl-CoA isomerase. AB - The purification to homogeneity of 3-cis-2-trans-enoyl-CoA isomerase from bovine liver is described. This procedure has also been successfully applied to the isolation of the enzyme from rat liver mitochondria. Its molecular mass was determined to be 30 kDa by several methods. Km of the isomerase for 3-cis dodecanoyl-CoA, the physiological intermediate in the beta-oxidation of oleic acid and of the 3-trans-isomer was determined to be 3.2 x 10(-5) M. The velocity of isomerization of the 3-trans-substrate is reduced 10-15 times. Inhibition experiments and pH-dependency of the reaction kinetics suggest the participation of a histidine residue in the isomerization. Protein analytical studies revealed that the N-terminus is blocked (acetylated). Cyanogen bromide cleavage of the purified enzyme resulted in five fragments. The N-terminus of one fragment is blocked. Partial amino-terminal sequences of two of the fragments were obtained by Edman degradation, a prerequisite for further studies on the structure of this isomerase on the DNA level. PMID- 2222860 TI - Detection of cathepsin B, plasminogen activators and plasminogen activator inhibitor in human non-small lung cancer cell lines. AB - Human non-small lung cancer cell lines HS-24 (established from a primary squamous cell carcinoma) and SB-3 (established from a metastasis of a primary adenocarcinoma of the lung into the adrenal gland) were analysed for the proteinases tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator inhibitor (PAI-1). The proteinases were characterized by activity measurements, inhibition studies, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis. Cell-associated proteinases were determined in cell lysates, secreted proteinases in cell conditioned culture media. Both cell lines were found to secrete uPA and PAI-1, whereas tPA could be detected only in HS-24 conditioned media. No cathepsin B activity could be detected in media of both cell lines. However, activation experiments and western blot analysis showed, that at least HS-24 secrete an inactive precursor. Cell lysates of HS-24 and SB-3 show PA activity, but on a low level. Cathepsin B activity was also found to be low in HS-24 lysates. However, SB-3 lysates show high cathepsin B activity. Further characterization of the proteinases by their sensitivity against several inhibitors suggests that they are similar to the corresponding proteinases of normal, nonmalignant cells. PMID- 2222861 TI - Subcellular distribution of adenine nucleotides in two Ehrlich cell lines metabolizing glucose. AB - Adenine nucleotide compartmentation and cytochrome redox state were studied in two Ehrlich ascites tumor cell lines incubated in the presence of 5mM glucose to show differences between their energy metabolisms. Changes in the subcellular distribution of adenine nucleotides were very different in both cell lines. Glucose seemed to energize the less malignant cell line, as shown by the asymmetry of the ATP/ADP ratios between cytosolic and mitochondrial compartments, but this was not the case for the more malignant cell line. The cytochrome contents were similar in both cell lines, but the degree of cytochrome oxidation was higher in the less malignant cell line; this result is in agreement with a higher oxygen consumption in the less malignant cell line. PMID- 2222862 TI - Nucleotide sequences of Bacillus stearothermophilus ribosomal protein genes: part of the ribosomal S10 operon. AB - Restriction fragments from Bacillus stearothermophilus chromosomal DNA were cross hybridized with the Escherichia coli ribosomal protein L2 gene rplB. A 2-kb EcoRI fragment which showed cross-hybridization was cloned into the M13 phage and sequenced by the dideoxy chain-terminating method. Comparison of the deduced amino-acid sequences with the corresponding sequences of E. coli ribosomal proteins showed that this fragment contains the region encoding the C-terminus of L2, the genes encoding S19, L22, S3 as well as the N-terminus of L16. Thus the organization of this gene cluster is the same as that in the S10 operon of E. coli. The deduced sequences of proteins L22 and S3, which have not been determined so far, were found to have 52% or 55% amino-acid identity, respectively, with those of the corresponding proteins in E. coli. The deduced B. stearothermophilus S19 protein sequence was in accordance with the reinvestigated protein sequence (H. Hirano, personal communication). PMID- 2222864 TI - The complete primary structure of alpha-lactalbumin isolated from pig (Sus scrofa) milk. AB - The complete amino-acid sequence of pig alpha-lactalbumin has been determined. It was obtained by microsequencing of the native protein and the peptides derived after tryptic or cyanogen bromide cleavage. The tryptic peptides were separated by a rapid microbore HPLC method. Pig alpha-lactalbumin is 122 amino acids long and differs from the bovine homologue by 26 exchanged residues. Of the two prolines present in bovine alpha-lactalbumin, one has been deleted in the pig structure. All previously sequenced alpha-lactalbumins have shown glutamic acid at position 49, which is known to be the active site in the homologous lysozyme c structure. This residue is replaced by phenylalanine in pig alpha-lactalbumin indicating that the pig protein is the first alpha-lactalbumin with complete loss of all lysozyme functional residues. PMID- 2222863 TI - Primary structure and oxygen-binding properties of the hemoglobin from guanaco (Lama guanacoe, Tylopoda). AB - The primary structure of the hemoglobin from guanaco (Lama guanacoe, Tylopoda) is presented. It could be separated into the chains by CM-cellulose chromatography. The sequences have been determined by automatic Edman degradation with the film technique or gas phase method, using the native chains and the tryptic peptides of the oxidized chains as well as a fragment obtained by acid hydrolysis. Guanaco hemoglobin has identical alpha-chains with alpaca and identical beta-chains with all Lama species with the exception that one guanaco in this study had alanine and serine in the ratio 1:1 in position beta 135 whereas a second individual had alanine only. Since the data suggest that the domesticated species llama and alpaca originate from the guanaco, it seems likely that beta 135Ala is the common form. Guanaco, llama, and alpaca show a comparable high blood oxygen affinity, caused by the substitution beta 2(NA2)His----Asn, as an adaptation to life at high altitude. PMID- 2222865 TI - Prevention and management of complications occurring during treatment with clomifene. PMID- 2222866 TI - Adverse reactions and interactions with aspirin. Considerations in the treatment of the elderly patient. AB - Aspirin (acetylsalicylic acid) is probably the most frequently used medication, and its use is generally uneventful. However, aspirin is also noted for numerous side effects and drug interactions that can complicate the course of therapy. The elderly, especially those with complicated medical histories, are more prone to the adverse effects of salicylates and may develop gastrointestinal tract bleeding, renal insufficiency, asthma and CNS toxicity. In the clinical situation, important drug interactions can occur with concurrent use of anticoagulants, sulphonylureas, diuretics, methotrexate and antacids. In long term aspirin therapy, enteric-coated or nonacetylated forms of aspirin are associated with fewer side effects and may be better tolerated. Monitoring of therapy (especially in the higher risk patient), with frequent assessments of the clinical state and measurements of serum creatinine, electrolytes and salicylate concentrations, may diminish the likelihood of toxicity. PMID- 2222871 TI - Medico-legal collars--time for a consensus to agree to disagree. PMID- 2222870 TI - Poisoning by thallium. A study of five cases. AB - Thallium poisoning seldom occurs in Spain. This article reports 5 cases of thallium poisoning, of which 4 of the patients belonged to the same family. The cases occurred in or near Granada between 1985 and 1987. The symptoms were initially gastrointestinal (vomiting, abdominal pain, gastrointestinal haemorrhage, etc.) in the case of the family poisoning, and a sensitive-motor polyneuritis in the fifth case. The diagnosis was established by analysis carried out in the authors' laboratory; urinary thallium concentrations were determined by atomic absorption spectrophotometry with graphite furnace and monovalent hollow cathode lamp. Each case was followed up to confirm the efficacy of the treatment; recovery from the poisoning was complete in all cases after 3 to 9 weeks. PMID- 2222868 TI - A risk-benefit assessment of estrogen therapy in postmenopausal women. AB - Estrogen therapy is extremely effective in relieving menopausal symptoms such as hot flushes, night sweats, urogenital atrophy and certain psychological symptoms. The short term side effects from this therapy are usually mild and self-limiting. They are more common in women who commence hormone replacement therapy some years after the menopause than in those who start treatment at about the time of the ovarian failure. Pre-existing gynaecological conditions such as fibroids and endometriosis can be worsened by estrogen therapy. The majority of published studies suggest a beneficial effect of postmenopausal estrogen therapy on cardiovascular and cerebrovascular disease. These effects may be mediated by favourable changes in lipids, but other mechanisms may also be involved. It is uncertain whether the adverse changes in lipids caused by progestogen therapy will reduce any of the benefits of estrogen therapy on the cardiovascular system. Osteoporosis is the major bone disease of the Western world; long term estrogen therapy will prevent its development in most postmenopausal women. The risk of endometrial carcinoma is increased with unopposed estrogen therapy; this increased risk appears to be abolished if a progestogen is added at an adequate dose and duration for each cycle. The risk of ovarian or cervical cancer is not increased with estrogen therapy. There may be an increased risk of breast carcinoma with long term postmenopausal estrogen use, but the studies show inconsistent results. PMID- 2222872 TI - Plasticity in the adult and neonatal central nervous system. AB - The adult nervous system is capable of plastic change; studies have shown that plasticity is part of normal adaptation to daily life as well as being part of the response to trauma. The structural substrates of plastic change are described, and the hypotheses for explaining functional recovery in adults following trauma are reviewed. Events in normal brain development are summarized, and experiments designed to investigate the processes involved are described. The brain of the neonate is a much more plastic structure than that of the adult, both in normal development and in response to trauma. Activity in pathways is an essential component for consolidation of connections, whether normal or compensatory. Experiments which elucidate the mechanisms of axonal/target recognition are described. Recent work on the possible development of therapeutic agents to enhance recovery from trauma, in both adults and neonates, is reviewed. An attempt is made to link the findings from basic research to the clinical field. PMID- 2222867 TI - Problems and pitfalls in the use of benzodiazepines in the elderly. AB - Benzodiazepines are frequently prescribed for elderly patients living in the community and for those in hospitals and institutions. Their use is more prevalent in women. Prolonged use of benzodiazepines is particularly likely in old age for the treatment not only of insomnia and anxiety, but also of a wide range of nonspecific symptoms. Long term users are likely to have multiple concomitant physical and psychological health problems. The distinction between benzodiazepine anxiolytics and hypnotics is difficult and somewhat arbitrary, since the differences between the compounds are less than their similarities, especially in respect of adverse reactions. Despite their wide therapeutic range, elderly patients are particularly prone to adverse reactions to benzodiazepines. The incidence of unwanted effects, predominantly manifestations of central nervous system depression, has been found to be significantly increased in hospitalised elderly patients, particularly in the frail elderly. Studies on unwanted effects during long term use are scarce, but there is some evidence of tolerance to side effects. However, benzodiazepines have been found to be frequently implicated in drug-associated hospital admissions. There is suggestive evidence that benzodiazepines, especially compounds with long half-lives, may contribute to the falls which are a major health problem in old age. The incidence of benzodiazepine dependence in elderly patients is unknown. The features of benzodiazepine withdrawal in the elderly may differ from those seen in young patients; withdrawal symptoms include confusion and disorientation which often does not precipitate milder reactions such as anxiety, insomnia and perceptual changes. Problems due to both adverse reactions and to benzodiazepine withdrawal may easily be overlooked in multimorbid elderly patients, particularly in those suffering from disorders of the central nervous system. There are numerous studies on benzodiazepine pharmacokinetics indicating that alterations, especially in distribution and elimination of certain compounds, occur in old age. Benzodiazepines with oxidative metabolic pathways and longer half-lives are likely to accumulate with regular administration. However, changes in pharmacodynamics may be more important to explain altered responses to benzodiazepines in the elderly. Although information on pharmacodynamics is still limited, there is convincing evidence of increased pharmacodynamic response in the elderly which may be further accentuated by disease factors. Since the variability of pharmacological response increases with age and is not always predictable, there is good reason at least to start therapy at lower doses and to titrate dosages individually. This may also be appropriate for the newer benzodiazepines, irrespective of advantageous pharmacokinetics.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2222873 TI - Brain abscess in the 1980s. AB - Brain abscess was reviewed in 24 patients admitted to University Hospital, Nottingham over a period of 3 years. Chronic ear infection was the most common predisposing factor, but in 11 patients the focus of infection remained unknown. CT scanning, carried out in all patients, was negative in one patient with clinical signs of meningitis. Polymicrobial and anaerobic infections were common. Actinomyces species were isolated in mixed culture from seven patients; in five the abscess was located in the cerebellum. Therapy was most often a combination of surgical drainage and antimicrobial therapy with beta-lactam agents and metronidazole. Evidence suggests that cefotaxime may offer a suitable alternative to chloramphenicol and benzylpenicillin in the treatment of brain abscess. PMID- 2222874 TI - Cranial intradural abscess management of 641 patients during the 35 years from 1952 to 1986. AB - The changes in management of intradural brain abscess at Groote Schuur Hospital for the 35 years 1952-1986 are reviewed. An improvement in mortality was found from 45% for 1952-1965 (period A), to 27% for 1966-1976 (period B); and lastly to 17% for 1977-1986 (period C). The improvement in the results was associated with the use of computed axial tomography (CT) and metronidazole. Abscesses secondary to ear infection were the commonest while those following trauma represented the second most frequent etiological group. Among the 26 cases of pulmonary origin in period C, 12 had pulmonary tuberculosis. Comparison of the outcome for patients presenting with Glasgow coma scale (GCS) 15 showed 39% mortality for period A compared with 3.5% in period C. Those patients who were comatose with GCS 8-3 had mortalities of 70 and 59% in periods A and C, respectively, indicating the importance of early diagnosis which has been facilitated by the advent of CT. PMID- 2222869 TI - An introduction to the clinical toxicology of volatile substances. AB - Acute poisoning with organic solvents and other volatile compounds now usually follows deliberate inhalation (volatile substance abuse) or ingestion of these compounds. Solvents from adhesives, typewriter correction and dry cleaning fluids, cigarette lighter refills (butane) and aerosol propellants are commonly abused. The major risk is that of sudden death. Arrhythmias leading to cardiac arrest are thought to cause most deaths, but anoxia, respiratory depression and vagal stimulation leading to cardiac arrest may also contribute, as may indirect causes such as aspiration of vomit or trauma. In the United Kingdom (UK), 3.5 to 10% of young people have at least experimented with volatile substance abuse and mortality is more than 100 per annum. The products abused are cheap and readily available despite legislation designed to limit supply. Volatile substance abuse is not illegal and only a minority of abusers are known to progress to heavy alcohol or illicit drug use. Prevention of abuse by education, not only of children but also of parents, teachers, retailers and health care workers, is important in limiting the problem. However, volatile substance abuse-related deaths are still increasing in the UK despite many measures aimed at prevention. Clinically, volatile substance abuse is characterised by a rapid onset of intoxication and rapid recovery. Euphoria and disinhibition may be followed by hallucinations, tinnitus, ataxia, confusion, nausea and vomiting. It is important not to further alarm the patient if signs of serious toxicity are present, since a cardiac arrest may be precipitated. Further exposure should be prevented and the patient resuscitated and given supplemental oxygen if necessary. Cardiac arrhythmias should be treated conventionally and respiratory failure managed supportively. Long term exposure to n-hexane is associated with the development of peripheral neuropathy, while prolonged abuse (notably of toluene or chlorinated solvents) can cause permanent damage to the central nervous system, heart, liver, kidney and lungs. Knowledge of the routes of absorption, distribution and excretion of volatile compounds, and of the rates governing these processes, is important in understanding the rate of onset, intensity and duration of intoxication, and rate of recovery after volatile substance abuse. In addition, such knowledge is helpful when the clinician is attempting to interpret the results of toxicological analyses performed on samples (blood, other tissues, urine) from such patients. Many volatile substances are partly metabolised, the metabolites being eliminated in exhaled air or in urine. Although metabolism normally results in detoxification, enhanced toxicity may also result as with carbon tetrachloride, chloroform, dichloromethane, n-hexane, trichloroethylene and possibly halothane.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2222875 TI - Brain abscess: with special reference to infection by pseudomonas. AB - Eighty cases of brain abscess treated in the University Hospital, BHU, Varanasi, India have been reviewed. Chronic suppurative otitis media was the commonest cause, followed by compound injuries. The overall mortality was 15%. In seven cases the causative organism was pseudomonas, resistant to most antibiotics. Prior to the availability of CT the mortality was 23.3%; after the routine use of CT for diagnosis the mortality fell to 10%. A high mortality (57%) was observed in patients who had pseudomonas. The best results were in patients who had been managed by excision of the abscess capsule. PMID- 2222876 TI - The management of patients with an intrinsic supratentorial brain tumour. AB - The management of patients presenting with supratentorial glioma between 1978 and 1986 is reviewed. Complete follow-up in 517 cases was obtained. One hundred and fifty eight patients were not submitted to any form of surgery, 299 patients were biopsied and 60 patients underwent craniotomy and internal decompression. The no surgery group contained a higher proportion of patients with poor prognostic indicators than either the biopsy or craniotomy groups. The craniotomy group consisted of patients with better prognostic indicators than the biopsy group, in particular, younger age and more favourable site, type and grade of tumour. This was reflected in the difference in outcome between the groups. Median survival was 14 months in the craniotomy group, four months in the biopsy group and 2.2 months in the no surgery group. The outcome in patients with histologically proven malignant gliomas was best in those patients who received radiotherapy. The craniotomy group had a median survival of 18.5 months, a two year survival of 48% and a five year survival of 9%. The median survival following radiotherapy of those patients with proven malignant gliomas who had a biopsy was 9.5 months with a two year survival of 16% and a five year survival of 2%. These results compare favourably with studies which have adopted a more aggressive approach, suggesting that outcome is determined as much by patient selection using favourable prognostic indicators as by the treatment itself. The need for prospective trials of the management of unselected consecutive glioma patients randomizing them to conservative and radical treatment groups in order to define the role of both conventional therapy and radical therapy is discussed. PMID- 2222877 TI - Facio-hypoglossal anastomosis for the treatment of facial palsy after acoustic neuroma resection. AB - Despite current micro-neurosurgical techniques the facial nerve may be irrecoverably damaged in up to 40% of operations for large acoustic neuromas. The results of 121 facio-hypoglossal anastomoses performed since 1960 for post operative facial palsy are reported. Patients began to recover facial function after an average of 2.5 months and at final follow-up 91% had good function (grade 2 or 3 according to Lye3). The functional result was dependent on the age of the patient, those over 50 years having a poorer, but still acceptable result. The result was not critically dependent on the delay in performing the procedure; in 10 patients with non-functioning but nevertheless intact nerves, the procedure was delayed for 12-15 months to allow for spontaneous recovery, with little detriment to outcome. There was no operative mortality and only minimal morbidity from hypoglossal loss. PMID- 2222878 TI - Recurrent lumbar disc protrusion. AB - Seventy-six patients who underwent re-operation for recurrent lumbar disc protrusion were analysed to define the pattern of disc recurrence and the outcome following the operation. Whereas recurrence after an L4/5 discectomy occurred at the same level in 66%, recurrence after an L5/S1 discectomy was as likely to occur at L4/5 as at L5/S1. Outcome was inversely related to the number of operations. A satisfactory outcome after the first procedure was usually associated with a satisfactory ultimate outcome. Associated complications were few but of a severe nature. PMID- 2222879 TI - Pain and spinal cysts in paraplegia: treatment by drainage and DREZ operation. AB - About 10% of paraplegics suffer from intractable pain. The onset of pain may be immediate or delayed for months to several years after the injury. The delayed onset of pain is highly suggestive of the development of a spinal cyst. This is a report of 18 paraplegics who developed a delayed onset of intractable pain who were found at the time of surgery to have associated spinal cord cysts. Treatment consisted of the dorsal root entry zone (DREZ) operation in addition to evacuation of the cyst. Burning pain was the most common complaint occurring years after the trauma. In this study we compared the relationship between the onset and character of the pain, the time of the spinal injury, the operative findings, and the results of the DREZ procedure and evacuation of the traumatic spinal cyst. We believe that the combination of paraplegia, pain and spinal cyst has not been emphasized in the neurosurgical literature although it is well known that cystic formation can follow spinal trauma. Two patients developed spinal cysts with nontraumatic lesions of the spinal cord. A single cyst was found in 14 patients while four had two separate cysts. The diagnosis was made on the basis of history and clinical examination with radiographic confirmation using delayed CT scan and myelography and more recently magnetic resonance imaging. Intraoperative ultrasound was employed in the study of some patients. All patients were treated with combined DREZ lesions and evacuation of the cysts with good pain relief in 77.7%. PMID- 2222880 TI - Trephine approach to anterior midline aneurysms--an initial communication. AB - The outcome of two groups of patients wtih midline aneurysms exposed by two different approaches was compared. The initial results support a clinical impression that a trephine approach has the following advantages: (1) adequate exposure with the best possible anatomical orientation and (2) a reduced morbidity. PMID- 2222881 TI - Intracranial ectopic pituitary tumour. AB - Pituitary tumours originating primarily from sites other than the sella turcica are rare. A case of an ectopic pituitary tumour in the region of the lesser wing of the sphenoid is reported. The patient presented with signs and symptoms of a progressive increase in intracranial pressure. CT scan appearances resembled those of a sphenoid wing meningioma. The vascular lesion was partially excised. Histology showed it to be a pituitary tumour. PMID- 2222882 TI - Giant cell tumour of the sphenoid bone with coincidental galactorrhoea--a case report. AB - A case of the rare giant cell tumour involving the sphenoid bone is reported. The usual presentation of these tumours is headache and cranial nerve deficits. This 25-year-old lady presented with oligomenorrhoea and galactorrhoea. Investigations demonstrated an asymptomatic erosive mass lesion in the sphenoid with suprasellar extension and extension into the nasopharynx. The tumour was partially resected via the transphenoidal route. The differential diagnosis and treatment of these lesions are discussed. PMID- 2222883 TI - Pituitary adenoma causing classical migraine. AB - A case of pituitary adenoma associated with classical migraine is described. The resolution of symptoms following removal of the tumour suggests a causal link. PMID- 2222884 TI - Traumatic aneurysm of the superficial temporal artery from fist injury. AB - A case of traumatic aneurysm of the superficial temporal artery (STA) from fist injury during a basketball game is described. The published cases of STA aneurysms secondary to sport trauma and their diagnosis and treatment are reviewed. PMID- 2222886 TI - Preservation of hearing in acoustic nerve tumours. PMID- 2222885 TI - Nimodipine and cerebral ischaemia following subarachnoid haemorrhage. PMID- 2222887 TI - Post-traumatic syringomyelia. PMID- 2222888 TI - Intra-operative brain swelling. PMID- 2222889 TI - Post-traumatic parosmia treated by olfactory nerve section. PMID- 2222890 TI - Distribution of GABA-like immunoreactivity in the central nervous system of the cockroach, Periplaneta americana (L.). AB - Gamma-aminobutyric acid (GABA) is one of the most frequently occurring neurotransmitters in the central nervous system. Using an antiserum against a GABA-protein conjugate, this has also been demonstrated for insects. The distribution of GABA-like immunoreactive neuronal elements within the central nervous system of the insect Periplaneta americana has been investigated by means of immunocytochemistry. An overview of the distribution of neuronal elements with GABA-like immunoreactivity (GLIR) in the brain is given. The ventral nerve cord was extensively investigated. The highest number of neurons with GLIR was estimated in the metathoracic ganglion (ca. 1000). The function of the suboesophageal ganglion as an inhibitory centre for the central nervous system was further confirmed by the high number of GABAergic elements and descending GABAergic pathways within the ventral nerve cord. A GABAergic innervation of skeletal musculature by so-called common inhibitory neurons was revealed for the legs of cockroaches. Nevertheless, GABA mainly seems to be a neurotransmitter in central interneurons. Identical distribution patterns of neuronal elements after immunofluorescence double-staining with anti-GABA antibodies and antibodies against the GABA-synthesizing enzyme glutamic acid decarboxylase demonstrated the high specificity of the anti-GABA serum used in this paper. PMID- 2222891 TI - Neuron-specific monoclonal antibodies raised against the low molecular weight fraction of a brain homogenate of the pond snail Lymnaea stagnalis immunoreact with neurons in the central nervous system of the cockroach, the guppy, the wall lizard, the rat and man. AB - Monoclonal antibodies were raised against the small molecular weight fraction (less than 30 kilodaltons) of an extract from 200 central nervous systems (CNS) of the freshwater snail Lymnaea stagnalis. In a first screening step the supernatants of the 297 emerging hybridomas were immunocytochemically tested on sections of the CNS of L. stagnalis. Sixty-six appeared to produce neuron specific antibodies, five reacted with non-neuronal elements. In a second step the 66 neuron-specific antibodies were tested on sections of the CNS of the guppy. Three reacted positively. In the third step the three antibodies were tested on the CNS of the rat. One antibody (Mab4H5) appeared to give positive results. In the snail brain Mab4H5 stains two identified giant neurons, one in the visceral ganglion (VD1), and one in the right parietal ganglion (RPD2)--these neurons form part of the network controlling the respiratory system--and a small number of cells in the cerebral ganglia (in the anterior and ventral lobes). Ultrastructural observations using immunogold labelling in VD1 showed the antigen to be localized to the secretory vesicles. In the guppy Mab4H5 stains fibres in the tectum and cell bodies in the reticular formation. In rat CNS staining was observed in Purkinje neurons of the cerebellum, in cortical pyramidal neurons and in neurons and fibres in other brain areas. Subsequent Mab4H5 staining of the CNS of the lizard, the cockroach and parts of the human CNS showed that these tissues also contain Mab4H5-positive neurons. In the human cortex and cerebellum the staining pattern appeared to be similar to that of the rat. On the basis of the results it is hypothesized that the antibody reacts with phylogenetically ancient amino acid sequences. PMID- 2222892 TI - Differential expression of protein kinase C isozymes in rat cerebellum. AB - Protein kinase C (PKC) is a family of enzymes found throughout the body, with the greatest diversity and concentration in brain tissue. To understand further the differential role of PKC isozymes in brain, we have raised antibodies against four PKC isoforms--alpha, beta I, beta II and gamma--using specific amino acid sequences predicted from cDNA sequences. On Western blot of rat cerebellar homogenate, these antibodies stained a band of Mr 80,000, a known molecular mass for PKC, except for anti-PKC(beta II), which stained an additional minor Mr 90,000 band. On rat cerebellar sections, specific sets of cells were stained by each antibody. In the molecular layer, stellate and basket cells were stained with anti-PKC(alpha) but not with anti-PKC(beta I), -(beta II), or -(gamma). Anti PKC (alpha) and anti-PKC(beta II) seemed to stain the Bergmann glial fibre. In the Purkinje cell layer, Purkinje cells were stained with anti-PKC[beta I) and (gamma). Anti-PKC (alpha) and -(beta II) were negative. Interestingly, a few Purkinje cells were not stained with anti-PKC(gamma). In the granule cell layer, both granule and Golgi cells were stained with anti-PKC(beta I) and -(beta II) but not with anti-PKC(alpha) or -(gamma). Glial cells were stained with anti PKC(beta II) but not with anti-PKC(alpha), -(beta I), or -(gamma). This study suggests a differential distribution of PKC isoforms in different cells, irrespective of their neurotransmitters. The presence of both positive and negative staining of Purkinje cells with anti-PKC(gamma) raised the possibility of their heterogeneity. PMID- 2222893 TI - Distribution of glutamic acid decarboxylase messenger RNA-containing nerve cell populations of the male rat brain. AB - The distribution of glutamic acid decarboxylase (GAD) mRNA was investigated throughout the rat brain by means of in situ hybridization. Hybridization was carried out with a 35S-radiolabeled cRNA probe transcribed from a cDNA from cat occipital cortex and cloned in a SP6-T7 promoter-containing vector. Fixed tissue sections were hybridized with 35S GAD probe (0.6 kb length). Signal was detected by means of film or emulsion autoradiography. The autoradiograms were semiquantitatively evaluated by means of computer-assisted image analysis. The results obtained with this evaluation were correlated with the results of the semiquantitative analysis of GAD immunoreactivity performed by Mugnaini and Oertel. Specific labeling was only observed in neuronal cell bodies, whereas no labeling was found over neuropil, glial and endothelial cells. The highest labeling was found in the bulbus olfactorius (internal plexiform and granular layers) and in the caudal magnocellular nucleus of the hypothalamus. Strong labeling was observed in the Purkinje layer of the cerebellar cortex, the interpeduncular nucleus, the interstitial nucleus of Cajal, the nucleus of Darkschewitsch and the suprachiasmatic nucleus. Intermediate or low levels of GAD mRNA were present in various brain nuclei, where gamma-aminobutyric acid (GABA) containing cell bodies had been observed with other techniques. Interestingly, a low level of GAD mRNA was found in the caudate-putamen and nucleus accumbens, where the vast majority of nerve cells is known to contain GAD immunoreactivity. Only a poor correlation was found between the present semiquantitative measurements of GAD mRNA content and previous analyses of the number of GAD immunoreactive cell bodies. The present study demonstrates that there exists a differential regional expression of GAD mRNA. The comparison with cell counts performed by immunocytochemistry suggests that some brain areas, such as caudate putamen and nucleus accumbens, contain a large number of GAD-immunoreactive cell bodies which express a low level of GAD mRNA. The opposite seems to be true for other nuclei, such as the globus pallidus, the zona reticulata of the substantia nigra and the inferior collicle, where few GAD-immunoreactive cell bodies contain high levels of GAD mRNA. In conclusion, the present study gives a low magnification map of GAD mRNA levels in the adult male rat brain. Marked biochemical heterogeneities may be present among GABA neuronal populations based on their expression of GAD mRNA. The comparison between the present in situ hybridization and previous immunocytochemical studies suggests that there may exist at least two populations of GABA neurons in the brain, having high and low levels respectively of both GAD mRNA and GAD enzyme. PMID- 2222894 TI - Immunohistochemical mapping of delta sleep-inducing peptide in the cat brain and hypophysis. Relationships with the LHRH system and corticotropes. AB - Using the indirect immunofluorescence method, the distribution of the delta sleep inducing peptide was studied in the cat brain and hypophysis. Delta sleep inducing peptide-like-immunoreactive cell bodies mostly visualized in colchicine pretreated animals were mainly found scattered throughout the diagonal band of Broca, the ventral septum and the anterior hypothalamic areas. A few immunoreactive cell somata were also seen in the ventrolateral hypothalamic area and more occasionally in the triangular septal nucleus. The heaviest concentrations of delta sleep-inducing peptide-like-immunoreactive varicose fibres and terminal-like structures were observed in the septo-preoptic region, in the median eminence and pituitary stalk. Some other brain regions supplied with few delta sleep-inducing peptide-immunoreactive fibres included the fimbria fornix, the dorsal part of the subfornical organ, the medial habenular nucleus and more caudally, the periaqueductal gray. Elution-restaining experiments revealed that delta sleep-inducing peptide-like immunoreactivity frequently occurred in luteinizing hormone-releasing hormone-immunoreactive neurons and vice versa. At the pituitary level, delta sleep-inducing peptide-like immunoreactivity was detected in most, if not all, melanocorticotropes of the pars intermedia and further in a large subpopulation of corticotropes mainly located in the zona tuberalis of the pars distalis. Taken together these anatomical findings support the view that delta sleep-inducing peptide (or a closely related molecular form) could play a modulatory role at various levels of the hypothalamo-pituitary system. PMID- 2222895 TI - Cancer and diabetes: are there similarities? PMID- 2222896 TI - The consumer's risk in clinical trials. AB - In any formal statistical test of the null hypothesis (the statement that a population parameter is equal to a specific value), there are two possible types of error. Type 1 or alpha error has occurred if the investigator rejects the null hypothesis when it is true. For example, an experimental treatment is declared an advance over standard treatment when it is not. Type 2 or beta error has occurred if the null hypothesis is not rejected when it is false. In this case, the investigator concludes that the experimental treatment is no different than the standard when it actually is. The two types of error can be conceptualized, respectively, as the consumer's risk and the producer's risk. In many reports of clinical trial methodology, it is the producer's risk that is emphasized. It is understandable why producer's risk would be of concern to authors of clinical studies. There are, however, numerous potential sources of consumer's risk. It is the latter type of risk that is the primary subject of this report. PMID- 2222897 TI - The phylogeny of oncology. AB - A review of reproductive biology and oncologic immunology reveals striking similarities between the tolerance of neoantigen as demonstrated in pregnancy and cancer. The author discusses the phylogeny of sexual reproduction and the oncologic condition, and suggests that an evolved mechanism of acquired tolerance to HLA-incompatible tissue necessitated by sexual reproduction consequently provides a mechanism for the tolerance of cancer. PMID- 2222898 TI - Subcutaneous interleukin-2 and interferon-alpha 2b in patients with metastatic renal cell cancer: the German outpatient experience. AB - A phase II clinical trial was conducted using subcutaneous recombinant human interleukin-2 (rIL-2, EuroCetus) and subcutaneous interferon-alpha 2b (rIFN-alpha 2b, Essex) in patients with advanced cancer. Safety and tolerance of this outpatient regimen were assessed in 17 patients with progressive metastatic renal carcinoma, 14 of whom were evaluable for clinical response to combined rIL-2 and rIFN-alpha 2b. In this study, rIL-2 was administered every 12 hours, at 1.5 million (Cetus) U/m2 on days 1 and 2, followed by 0.3 million U/m2 5 days per week for 6 consecutive weeks. Concomitantly, rIFN-alpha 2b was given as 5 million U/m2 three times weekly for 6 consecutive weeks. Patients presenting with stable or regressive disease after 6 weeks of rIL-2 and rIFN-alpha 2b (11 of 14) were scheduled to repeat combination therapy. After one treatment cycle, five of 14 patients presented with partial remission; two of these patients achieved complete regression of metastatic lesions. After therapy, six patients have been in stable disease for up to 8 months. toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (World Health Organization criteria) fevers, chills, malaise, nausea and/or vomiting, and anorexia in 70% to 100% of patients treated. After 6 weeks of rIL-2 and rIFN-alpha 2b, laboratory evidence of treatment-related hypothyroidism and hyperthyroidism was obtained in one and four patients, respectively. Immunogenicity of sc rIL-2 was mostly limited to the development of nonneutralizing antibodies that occurred in approximately 40% of patients. None of the patients exhibited antibodies specific to rIFN-alpha 2b. PMID- 2222900 TI - Chronic recurrent aphthous stomatitis: oral treatment with low-dose interferon alpha. AB - Recombinant human interferon alfa-2a (HuIFN alpha) was administered orally once daily in a low concentration (1,200 IU/day) to nine patients with chronic recurrent aphthous stomatitis (RAS), and a placebo solution was given to 10 control chronic RAS patients in a double-blind study. All HuIFN alpha-treated patients had total remission of their aphthae within a 2-week period, while placebo control patients had no change in their condition. The 10 placebo control patients were then treated with HuIFN alpha in a manner identical to that used for the initial principal group. Within a 2-week period, all original placebo patients had complete remission of their aphthae. Eleven of the patients did not have a recurrence of RAS during a subsequent 6-month observation period. Eight patients had recurring aphthae; however, the lesions were resolved by retreating with oral HuIFN alpha for less than 1 week. PMID- 2222899 TI - Phase II study of recombinant interferon alpha-C in patients with metastatic renal cell carcinoma. AB - Recombinant interferon alpha-C is a new strain of the alpha interferon family. It was given to 33 patients with measurable metastatic renal cell carcinoma of whom 31 were evaluable. Protocol consisted of 3 million U/d for 2 weeks, then 3 million U/m2 every other day until progression. No complete response was observed. Three patients (9.7%) had partial response for a mean duration of 5.6 months and eight patients (25.8%) were stabilized for a mean of 4.3 months. Responsive sites were mainly lung, bone, and kidney, while side effects were generally mild. better results were observed in previously nephrectomized patients who had not received chemotherapy or hormonotherapy for recurrent or metastatic disease (p less than 0.05), and also in patients with a brief disease free interval and short delay from presenting symptoms of the primary tumor until interferon treatment (p less than 0.05). Median survival was significantly longer in responders than in progressors (p less than 0.05). We suggest that the efficacy of recombinant interferon alpha-C in a low-dose regime versus other types of interferon as first-line therapy for inoperable, metastatic, or locally recurrent renal cell carcinoma should be investigated in a prospective, controlled, randomized study. PMID- 2222901 TI - Inhibition of SA-1 tumor growth in mice by human leukocyte interferon alpha combined with low-level direct current. AB - A preliminary study of the antitumor effect of partially purified human interferon alpha (IFN-alpha) and low-level direct current (DC) was carried out using a murine subcutaneous SA-1 experimental tumor model. Tumor-bearing animals were treated with 5 x 10(4) IU IFN-alpha peritumorally, or with 0.6 mA DC current for 15 minutes daily, for 6 consecutive days. Antitumor effect was manifested 2 days after the beginning of each treatment modality. Combined treatment with DC current applied immediately after IFN-alpha application was more effective than IFN-alpha treatment alone (P less than 0.005), but not significantly better than DC current treatment (P less than 0.5). The results indicate that the combined treatment with IFN-alpha and DC current can be effective in tumor therapy; however, further work is required to determine optimal scheduling. PMID- 2222902 TI - The effects of cyclophosphamide on the toxicity and immunogenicity of ricin A chain immunotoxin in rats. AB - We conducted a study to determine if treatment with cyclophosphamide (CY) could suppress the formation of anti-murine and anti-ricin A chain antibodies in rats treated with a murine monoclonal antibody-ricin A chain immunotoxin (IT). Female Sprague-Dawley rats received intravenous doses of IT at a dose of 5 mg/kg body weight alone or in combination with CY at a dose level of either 10 or 20 mg/kg body weight. The IT was given as one or two courses consisting of five consecutive daily intravenous injections (days 0 to 4, or days 0 to 4 and days 21 to 25 of the study). Cyclophosphamide was given on days 2, 4, 6, 13, and 17 of the study to the group receiving a single course of IT; additional doses of CY were administered on days 23, 25, and 27 to the group receiving two courses of IT. On days 4, 14, 21, 28, and 35, animals from each group were evaluated for antibodies to murine IgG and ricin A chain, and for clinical laboratory parameters and histopathology. Animals receiving IT alone developed significant titers of both anti-murine and anti-ricin A chain antibodies. Compared with the response in the animals receiving single-course IT, the response to both of the components of the IT was significantly increased on days 28 and 35 in the animals receiving a second course of IT. The groups receiving a combination of either one or two courses of CY and IT demonstrated a significantly decreased antibody response to both the murine IgG and the ricin A chain compared with the group receiving IT alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222903 TI - Application of scattering techniques in the domain of amphiphiles. AB - Light and neutron scattering techniques are discussed in connection with experiments on micellar solutions of gangliosides--amphiphilic molecules of biological origin. Micellar properties, like molecular weight, hydrodynamic radius and shape, are obtained with precise scattering measurements in conditions of negligible intermicellar interactions. It has also been verified that the GM1 ganglioside micelle does not change molecular weight and shape on addition of salt. Scattering techniques are also shown to be useful in studying intermicellar interactions, like the Coulomb repulsion between GM1 micelles, in the regime fo the long-range interactions obtainable at very low ionic strength. PMID- 2222904 TI - Interactions of lipases with lipid monolayers. Facts and questions. AB - Among the proteins, lipolytic enzymes provide a valuable model for studying protein-lipid interactions. Lipases having a catalytic action which is strictly dependent upon the presence of a lipid interface were used in the present study in order to gain better insight into protein-lipid interactions. Most of the data presented here were obtained using the monolayer technique, by recording (either independently or simultaneously) the lipolytic activity, the amount of protein adsorbed to the lipid monolayer, and the surface pressure variations following protein adsorption. Several non-enzymatic proteins were used as controls in order to determine how lipase behaviour differs from that of other proteins. At all initial surface pressures tested, with zwitterionic monolayers, a good correlation was observed between the amount of lipase bound to the monolayer and the surface pressure increase, in agreement with previous studies. Conversely, with neutral lipid monolayers the amount of lipase bound to the monolayer was not found to be surface pressure dependent. This latter behaviour observed with lipases on neutral films is not specific to lipases, since it was also observed with bovine serum albumin and beta-lactoglobulin A. Lipase activity in the presence of various proteins was investigated with monomolecular films of glycerol didecanoate, either at constant surface area or at constant surface pressure. Depending upon the nature of the lipase and the protein, inhibition of lipase activity was either observed or not. Inhibition was correlated with a decrease in lipase surface concentration. The ability of the various proteins to inhibit lipolysis is: (i) a function of their excess versus lipase in the bulk phase, and: (ii) correlated with their penetration capacity (i.e., the initial rate of surface pressure increase of a glycerol didecanoate monolayer having an initial surface pressure of 20 dyn/cm, after the injection-of the protein). Since lipase inhibition was observed with low surface densities of inhibitory proteins, a long-range effect is probably involved in the mechanism of interfacial lipase inhibition. The nature of the ionic charge added to the monolayer by the protein is not critical for determining lipase adsorption or desorption. It is hypothesized that the lack of lipase adsorption to, or desorption from, the lipid monolayer results from a change in the organization of the hydrocarbon moiety of the lipid. PMID- 2222905 TI - CPA/Niccol lecture. Leisure and lifestyle in later life. PMID- 2222907 TI - Leg ulcers. Prevention is better than cure. PMID- 2222906 TI - Pressure area care. How effective are sheepskins? PMID- 2222908 TI - Dental care: the problem of being 'long in the tooth'. PMID- 2222909 TI - Living wills: going gently into the dark night. PMID- 2222910 TI - Understanding confusion. PMID- 2222912 TI - The ACE objectives. PMID- 2222911 TI - Nursing models: team work for personal patient care. PMID- 2222913 TI - Focus on support for those who care. PMID- 2222914 TI - The Alzheimer's Disease Society. PMID- 2222916 TI - "Genetic counseling": a "new" discipline with increasing impact on individuals, families and society. PMID- 2222915 TI - The time is ripe for a takeover. PMID- 2222918 TI - The fetal akinesia deformation sequence. A fetopathological approach. AB - In this paper we review the present knowledge on the etiological factors and pathogenetic mechanisms of the fetal akinesia deformation sequence, based on a fetopathological approach. Special attention is given to two sever, lethal subgroups i.e. the Pena-Shokeir I syndrome and the lethal multiple pterygium syndrome. PMID- 2222917 TI - The lethal multiple pterygium syndrome: a nosological approach. AB - The Lethal Multiple Pterygium Syndrome (LMPS) is characterised by lethality, multiple pterygia and frequently hydrops and/or hygroma colli. In this paper, we review 36 published cases, discuss the clinical features, pathogenesis, differential diagnosis and mode(s) of inheritance. Most cases were diagnosed in the second trimester of pregnancy by hydrops/hygroma colli at ultrasonography and/or stillbirth. Pterygia were present in two or more body areas overlying predominantly the large joints; joint contractures always accompany the pterygia. Facial features are: hypertelorism, antimongoloid slanting of the palpebral fissures, flattened nasal bridge with hyproplastic nasal alae, micrognathia and cleft palate. Lung hypoplasia is the rule. Except for hypoplastic bones there were no consistent radiological findings. Cerebral abnormalities were occasionally found; muscular atrophy was mentioned in a number of cases. Chromosome abnormalities were never reported. Based on clinical presentation we propose an "early type" of LMPS and a "late type" of LMPS. Besides, we consider the cases described by Herva as a separate "Finnish type" LMPS. We found an excess of male cases, especially in young fetuses. LMPS is known as an autosomal recessive inherited trait. X-linked recessive inheritance however cannot be excluded in an isolated male case or in a sibship with males only. The Finnish type of LMPS appears to be an autosomal recessive trait. PMID- 2222919 TI - A retrospective study of pregnancy complications among 828 cases of arthrogryposis. AB - 828 cases with multiple congenital contractures (arthrogryposis) were categorized and histories were reviewed to identify pregnancy complications. 53.0% of cases had a specified diagnosis or known cause and no diagnosis was found for 47.0% of which 27.2% were though to probably have a genetic basis and 19.8% were of unknown etiology. Our data provides no evidence to support the suggestion that arthrogryposis is frequently a result of environmental or structural causes including uterine structural anomaly, intra-uterine infection, etc. Normal frequencies of bleeding, hormone treatment during gestation, amniotic fluid leakage, uterine anomaly, maternal illness, and maternal and paternal age were noted. Apparent, increased frequencies of twinning, severe nausea, polyhydramnios and oligohydramnios were observed. In particular, the frequency of polyhydramnios was dramatically increased among lethal cases (vs survivors) and thus, polyhydramnios appears to be a poor prognostic sign when associated with decreased fetal movement. Large case control studies with complete pregnancy histories are needed to confirm these results and to definitively identify pregnancy complications that are useful "flags" to indicate decreased fetal movement in utero and thus, aid in the identification of primary causes of arthrogryposis. PMID- 2222920 TI - The echographic diagnosis of fetal akinesia. A challenge towards etiological diagnosis and management. PMID- 2222921 TI - The fetal akinesia sequence: pitfalls and difficulties in genetic counseling. AB - In this paper, we review the difficulties of genetic counseling in the fetal akinesia sequence. The ongoing progress in the nosological subclassification, thanks to the increasing number of fetopathological studies, is the basis and a condition sine qua non for accurate genetic counseling. PMID- 2222922 TI - On the nosology of moderate mental retardation with special attention to X-linked mental retardation. A diagnostic genetic survey of 274 institutionalized moderately mentally retarded men. AB - In this paper we report the results of a genetic-diagnostic survey of 274 institutionalized moderately mentally retarded adult males and compare these data with those from our previous studies in the severely mentally retarded and from a comparable population of 262 institutionalized moderately mentally retarded males and females (The Borgenstein experience). Special attention is paid to the nosology of X-linked mental retardation and familial mental retardation in general. PMID- 2222923 TI - Angelman's syndrome and 15q11-q13 deletion. AB - We discuss the results of cytogenetic reinvestigation in 10 patients with Angelman's syndrome reexamined during the last year. A deletion with 15q11-13 could be demonstrated in 6 of them, confirming that with the available cytogenetic techniques a 15q11-13 deletion is visible and detectable in at least half of the patients with this MCA/MR syndrome. On the other hand, the deletion could not be seen in two affected siblings. This indicates that de novo visible 15q11-13 deletions with low recurrence risk and autosomal recessively inherited cases combine to give an overall sib recurrence risk of less than 25%. PMID- 2222924 TI - Craniosynostosis and low middle frequency perceptive deafness in mother and son. A distinct entity? AB - A distinct entity?: In this report we describe the hitherto unreported association of low and middle frequency perceptive deafness and craniosynostosis in mother and son. The occurrence of hearing loss in the craniosynostosis syndromes is briefly reviewed. PMID- 2222925 TI - Anodontia as the sole clinical sign of the ectrodactyly-ectodermal dysplasia cleft lip (EEC) syndrome. AB - In this report we present another family with oligosymptomatic expression of the EEC syndrome. A mother with complete absence of the permanent teeth had two children with split hand/split foot deformity, as typically seen in the EEC syndrome. Cleft lip/cleft palate was also present in one of them. The great variability in expression of this autosomal dominant syndrome is discussed and the difficulties in genetic counseling are emphasized. PMID- 2222926 TI - Hydrops fetalis associated with red cell pyruvate kinase deficiency. AB - A hydrops fetalis and multicystic encephalomalacia were diagnosed in a neonate who was one of twins. The co-twin had died 5 weeks prior to delivery. The most likely explantation for both hydrops and multicystic encephalomalacia was fetal anemia caused by a red cell pyruvate kinase deficiency, and aggravated by an intrauterine disseminated intravascular coagulation. PMID- 2222927 TI - True hermaphroditism: a new case with complex mosaicism. AB - True hermaphroditism is a very rare disorder of human sexual differentiation. In the medical literature, more than 450 cases are described, and about 250 true hermaphrodites have been subjected to chromosome studies. A 21-year-old "man" was examined because of genital and phenotypic abnormalities: clinical, surgical and laboratory investigations showed a true hermaphroditism, with a quadruple mosaicism 45,X/46,XX/46,XY/47,XXY. We believe that this is the first case in which this peculiar type of multiple mosaicism has been documented. PMID- 2222928 TI - A possible negative correlation between the frequency of chromosome lesions induced by folate-deficiency and age in individuals with the fra-Xq27.3 syndrome. PMID- 2222929 TI - In memory of Professor A. Franceschetti (1896-1968). PMID- 2222930 TI - Synthesis and structure of cytosine dichloride cuprate: direct binding of copper to cytosine. AB - Dichlorobis(cytosine)copper(II), [CuCl2-(C4H5N3O)2], Mr = 356.65, monoclinic, P2(1)/n, a = 8.399 (2), b = 13.773 (2), c = 10.775 (2) A, beta = 90.8 (2) degrees, V = 1246.3 (9) A3, Z = 4, Dx = 1.901 Mg m-3, lambda (Mo K alpha) = 0.7107 A, mu = 2.195 mm-1, F(000) = 716, T = 298 K, R = 0.032, wR = 0.037 for 2313 reflections greater than 2 sigma(F). The crystal structure of the title compound consists of two crystallographically independent cytosine molecules attached together through the direct bonding of a Cu2+ ion with two N atoms of the pyrimidine rings. In addition to the N atoms, the Cu ions are coordinated to two Cl atoms forming approximately a square-planar environment. The bond distances of Cu to Cl(1), Cl(2), N(3) and N(3') atoms are 2.299 (1), 2.267 (1), 1.985 (4) and 1.996 (3) A, respectively. Packing of the Cyt(I)-CuCl2-Cyt(II) complex in the crystal is ensured by an extensive extramolecular N--H...Cl and N- H...O network. Hydrogen bonds involving Cl, O and H atoms of the neighboring Cyt(I) and Cyt(II) induce a slight distortion in Cu--Cl, C = O distances but do not significantly affect intramolecular bond lengths and angles in the cytosine rings and their flatness. PMID- 2222931 TI - Structure of the cyclohexapeptide cleromyrine II trihydrate. AB - C29H40N6O7.3H2O, Mr = 638.7, trigonal, P3(1)21, a = 14.190 (2), c = 29.833 (4) A, V = 5202 (1) A3, Z = 6, Dx = 1.22 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 7.8 cm-1, F(000) = 2052, T = 291 K, R = 0.069 for 1942 observed reflections. The new cyclohexapeptide cleromyrine II was isolated from Clerodendrum myricoides. Its structure was established by spectroscopic and X-ray diffraction methods as cyclo(-Gly-Tyr-Gly-Pro-Leu-Pro-). The conformation essentially consists of two beta-turns including the Pro residues and one central very short antiparallel beta-sheet stabilized by two intramolecular hydrogen bonds: N(Tyr2)...O(Leu5) = 2.94 (2) A and N(Leu5)...O(Tyr2) = 3.02 (2) A. PMID- 2222932 TI - Structure of (+)-(7S,SS)-1,2,3,5,6,7-hexahydro-7-methyl-8-(p-tolylsulfinyl)-5 indoli zinone. AB - C16H19NO2S, Mr = 289.39, orthorhombic, P2(1)2(1)2(1), a = 11.467 (5), b = 17.207 (8), c = 7.566 (4) A, V = 1493 (2) A3, Z = 4, Dx = 1.29 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.07 cm-1, F(000) = 616, T = 296 K, R = 0.049, 928 unique observed reflections. The structure determination combined with the known S configuration at the sulfur site discloses the stereochemistry of the title compound to be 7S and SS. PMID- 2222933 TI - Structure of (+/-)-(1R*,4S*,6S*)-1-benzyloxy-4,8,11,11-tetramethyl-6- phenylthio bicyclo[5.3.1]undec-7-en-3-one. AB - C28H34O2S, Mr = 434.64, triclinic, P1, a = 8.9868 (7), b = 11.2933 (11), c = 12.3497 (6) A, alpha = 80.937 (6), beta = 73.108 (5), gamma = 87.405 (7) degrees, V = 1184.32 (15) A3, Z = 2, Dx = 1.22 g cm-3, mu = 1.509 cm-1, Mo K alpha radiation, lambda = 0.7107 A, F(000) = 468, T = 298 K, R = 0.0583 for 6924 reflections [Fo greater than or equal to 4 sigma(Fo)]. The cyclooctane portion of the [5.3.1] ring system is in the boat-chair conformation while the cyclohexene portion assumes the boat conformation. The carbonyl group and the alkene group are nearly parallel in the molecule with a dihedral angle of 14.9 (1) degree between planes through the two groups. Ring strain appears to cause distortion in the alkene functionality. The bond length [C7-C8 1.343 (2) A] is long for an isolated C-C double bond. The torsion angles deviate between 3.7 (2) and 18.39 (14) degrees (absolute values) from ideality. This twist in the alkene group is reflected in the non-planarity of the group [max. deviation -0.177 (2) A for C9] and in the dihedral angle between the nearly planar portions (C6,C7,C8,C11 and C7,C8,C9,C16) which is 12.1 (1) degrees. PMID- 2222935 TI - Structure of 6 alpha-methyl-3,20-oxo-1,4,9(11)-pregnatrien-17 alpha-yl acetate. AB - C24H30O4, Mr = 382.5, orthorhombic, P2(1)2(1)2(1), a = 13.091 (2), b = 19.711 (1), c = 8.242 (1) A, V = 2126.7 (5) A3, Z = 4, Dx = 1.195 Mg m-3, lambda(Cu K alpha) = 1.54184 A, mu(Cu K alpha) = 0.56 mm-1, F(000) = 824, T = 295 K. Final R = 0.045 for 2446 unique reflections. The planar A ring is bent relative to the rest of the steroid skeleton. The B ring has a typical chair conformation and the C and D rings assume 13 beta,14 alpha-half-chair and 13 beta-envelope conformations, respectively. The conformation of the progesterone side chain is similar to the conformation observed in other 17 alpha-ester pregnanes: C16-C17 C20-O20 torsion angle -27.4 (3) degrees. PMID- 2222934 TI - Structure of (+/-)-(1S*,3S*)-3-hydroxy-8,11,11-trimethyl-9-oxobicyclo[5.3.1]undec 7- en-1-yl benzoate. AB - C21H26O4, Mr = 342.43, monoclinic, P2(1)/n, a = 7.211 (2), b = 19.521 (6), c = 12.674 (3) A, beta = 95.04 (2) degrees, V = 1777.2 (8) A3, Z = 4, Dx = 1.28 g cm 3, Mo K alpha radiation, lambda = 0.7107 A, mu = 0.8152 cm-1, F(000) = 736, T = 163 K, R = 0.0632 for 3754 reflections [Fo greater than or equal to 4 sigma(Fo)]. The molecules exist as hydrogen-bonded dimers [O14-H14...O16 (related by -x, 1-y, 1-z), O14...O16 2.775 (2), H14...O16 1.93 (2) A, O14-H14...O16 175 (2) degrees] which stack in columns along b. Distortion at the bridgehead double bond is observed. Deviations from ideal values for the torsion angles around the double bond, C7-C8, are as large as 17.8 (2) degrees. The dihedral angle between planes through C6-C7-C8-C11 and C7-C8-C9-C15, the planar portions of the alkene moiety, is 13.4 (9) degrees. The Csp2--Csp3 bond lengths involving C7 are asymmetric with C7-C6 1.501 (2) and C7-C11 1.538 (2) A. The bond length C7-C8 is elongated [1.352 (3) A] for a C-C double bond. The enone system is also non-planar [max. deviation -0.404 (2) A for C10]. PMID- 2222936 TI - Structure of (+/-)-encecanescin. AB - C24H30O4, Mr = 382.5, orthorhombic, P212121, a = 13.091 (2), b = 19.711 (1), c = 8.242 (1) A, V = 2126.7 (5) A3, Z = 4, Dx = 1.195 Mg m-3, lamba (Cu K alpha) = 1.54184 A, mu(Cu K alpha) = 0.56 mm-1, F(000) = 824, T = 295 K. Final R = 0.045 for 2446 unique reflections. The planar A ring is bent relative to the rest of the steroid skeleton. The B ring has a typical chair conformation and the C and D rings assume 13 beta,14 alpha-half-chair and 13 beta-envelope conformations, respectively. The conformation of the progesterone side chain is similar to the conformation observed in other 17 alpha-ester pregnanes: C16-C17-C20-O20 torsion angle -27.4(3) degrees. PMID- 2222938 TI - Electrostatic properties of cytosine monohydrate from diffraction data. AB - The charge density distribution in deuterated cytosine monohydrate [4-(2H2)-amino 2(1H)-(1-2H)-pyrimidinone], C4H2D3N3O.D2O, Mr = 134.15, monoclinic, P2(1)/c, a = 7.714 (1), b = 9.825 (1), c = 7.506 (2) A, beta = 100.52 (1) degrees, Z = 4, has been determined from 1432 X-ray reflections [sin theta/lambda less than 1.15 A-1, Mo K alpha, lambda = 0.7093 (1) A] collected at 82 (2) K. Least-squares structure refinement assuming Stewart's rigid pseudoatom model gave R(F) = 0.041, with all nuclear positions and H/D anisotropic thermal parameters having fixed values previously determined by neutron diffraction. The cytosine and water molecules are both electrically neutral within experimental error (0.09 e). Molecular dipole moments are mu = 8.0 (1.4) debye for cytosine and 2.3 (3) debye for water. For the doubly hydrogen-bonded cytosine dimer (N1-D1...N3', N4-D4...O2') isolated from the crystal, the electrostatic energy of interaction is estimated to be -96 (27) kJ mol-1. Maps of the electrostatic potential for molecules isolated from the crystal indicate that the electronegativity of the hydrogen-bonding acceptor sites can be ranked with the water O atom, cytosine N(3) and carbonyl O(2) in decreasing order. PMID- 2222937 TI - Structure of 3,4,5-trihydroxybenzoic acid octyl ester (octyl gallate) dihydrate at 123 K. A non-mesogenic amphiphilic molecule. AB - The crystal structure of 3,4,5-trihydroxybenzoic acid octyl ester (octyl gallate) dihydrate, C15H22O5.2H2O, is triclinic, P1, with a = 6.617 (1) [6.648 (1)], b = 9.956 (2) [9.995 (3)], c = 14.088 (4) [14.327 (7)] A, alpha = 79.08 (2) [79.78 (3)], beta = 85.58 (3) [86.59 (4)], gamma = 70.80 (2) [70.99 (3)] degrees, V = 860.5 A3, Z = 2, Dx = 1.229 1.229 [1.183] g cm-3, lambda(Mo K alpha) = 0.7093 A, mu = 0.58 cm-1, F(000) = 344 at 123 K [290 K]. The structure was solved by direct methods and refined to R(F2) = 0.059 for 302 parameters and 3655 observations. The alkyl chain of the molecule is in the fully extended conformation. The molecular packing is head-to-head bilayer with interdigitizing alkyl chains. The gallate head groups are hydrogen bonded with the water molecules to form a strong system of intra- and intermolecular hydrogen bonds consisting of finite and infinite chains. The crystals undergo crystal-to-crystal phase transitions at 365 K on heating and at 333 K on cooling, but despite the molecular packing which is analogous to that of the mesogenic alkyl glycosides, there is no thermotropic liquid crystal phase prior to the formation of the isotropic liquid phases at 376 K. Similary, no lyotropic liquid crystal phases are observed at room temperature in contact with a mixture of water and propanediol in which the crystals are soluble. PMID- 2222939 TI - Alpha,beta-dehydro residues in the design of peptide and protein structures. AB - The results of X-ray studies on 19 structures containing dehydro residues have been analysed. The observed average C alpha = C beta distance in the dehydro residues is 1.331 (2) A. The average values of the C alpha = C beta - C gamma bond angle in dehydro-Phe and dehydro-Leu are 131.2 (2) and 127.3 (1) degrees, respectively. The dehydro residue is essentially planar. A beta-turn of type II is formed if the dehydro residue is placed either at the (i + 1) or at the (i + 2) corner position of the beta-turn. If the dehydro residues occur consecutively in an amino-acid sequence, the backbone folds into an alternating right- and left handed alpha-helix. The peptide bond is planar in all these structures. The beta turn is stabilized by an intramolecular hydrogen bond between CO of the ith and NH of the (i + 3)th residue. PMID- 2222940 TI - The stereochemistry of the water molecules in the hydrates of small biological molecules. AB - An examination of the stereochemistry of the water molecules in the hydrates of amino acids and peptides, carbohydrates, purines and pyrimidines, and nucleosides and nucleotides, reveals a variety of hydrogen-bonded configurations within a radius of 3.0 A from the water oxygen atom. Water molecules which accept one hydrogen bond are more common than those that accept two, by a factor of 1.4. There are nine examples where the water is not a hydrogen-bond acceptor, but only one where it does not donate two hydrogen bonds. Of the 621 OWH...A bonds examined, 15% were three centered and 2% were four centered or three-center bifurcated. The amino-acid and peptide hydrates displayed the greatest variety with 15 different hydrogen-bond configurations. The coordination of the donor and acceptor atoms within 3.0 A of the water oxygen atom ranged from two to seven. PMID- 2222941 TI - The effects of caffeine on blood pressure in the work environment. AB - The ambulatory blood pressure and heart rate of twelve healthy volunteers were monitored on two separate days in the participants' work environment. All subjects were studied in a double-blind crossover design while they consumed caffeinated or decaffeinated coffee. We examined them at rest, during a standardized mental arithmetic task, and for 6 h of ambulatory monitoring in their regular work setting (research facility and hospital). On days of drinking caffeinated coffee, both systolic and diastolic blood pressure were consistently elevated at all time points (P less than .0005). In response to the mental arithmetic task, the increase in systolic blood pressure over the resting value was particularly exaggerated on caffeinated coffee (P = .0003). For heart rate, there were no effects from caffeine. The study demonstrates that the blood pressure-elevating effects of caffeine, well-known from laboratory studies, are sufficiently robust to be evident in patients' uncontrolled work environments. It implies the importance of caffeine restriction for hypertensive patients. It also indicates the utility of ambulatory blood pressure techniques in studying the blood pressure effects of various nutritional factors taken ad lib in the real world. PMID- 2222943 TI - Effect of captopril injection in patients with moderate to severe hypertension. AB - The effect of intravenous captopril was studied in 24 white patients who had moderate to severe hypertension. Patients received incremental doses of 1 to 10 mg delivered at 10 min intervals over 50 to 80 min. Blood pressure (BP) was lowered within 5 to 10 min after the initial dose was administered and continued to decline, reaching a maximum response after 20 min (2 to 4 mg). At this time group mean BP fell from 175 +/- 3/111 +/- 1 to 166 +/- 3/97 +/- 2 mm Hg (P less than 0.01). Additional dose increments to an average cumulative dose of 40 mg did not increase the initial effect. No adverse side effects or symptomatic hypotension occurred in any subject. There was a significant correlation between diastolic BP decreases observed in response to intravenous captopril and subsequent long-term oral captopril therapy. The addition of hydrochlorothiazide increased the proportion of patients reaching normotension. We conclude that small intravenous bolus injections of captopril appear to be effective rapidly and are well tolerated in moderate to severe essential hypertension. Short-term intravenous administration seems to predict the response to chronic oral captopril therapy. PMID- 2222942 TI - Effects of n-3 fatty acids in essential hypertension. AB - We examined the effects on blood pressure, plasma lipoproteins, and platelet function when marine oil supplements (rich in n-3 fatty acids) or vegetable oil supplements (rich in n-6 fatty acids) were added to the usual diets of patients with mild essential hypertension. In a randomized, double-blind, parallel-group study, patients received 50 g of either marine oil (n = 8) or vegetable oil (n = 8) daily for 6 weeks following a baseline observation period. Diastolic blood pressure declined during treatment with fish oil (mean +/- SEM, 96 +/- 2 v 89 +/- 2 mm Hg, P = .02), but did not change with vegetable oil (92 +/- 1 v 94 +/- 1 mm Hg). Systolic blood pressure did not change significantly during either treatment. Serum triglycerides declined (by approximately 30%) in patients receiving only marine oil, but total cholesterol, LDL-, HDL-, HDL2-, and HDL3 cholesterol-subfractions and apolipoproteins A-I and B were unchanged in both treatment groups. Bleeding time increased by 33% during treatment with marine oil but did not change with vegetable oil supplements. Marine oil did not alter in vitro platelet aggregation thresholds. The lack of a significant correlation between blood pressure changes and platelet membrane fluidity, plasma renin activity, aldosterone, norepinephrine, or epinephrine suggests that these variables did not mediate the antihypertensive effect of the marine oil. We conclude that large doses of marine oil reduce diastolic blood pressure, lower triglycerides, and increase bleeding time in patients with mild hypertension. PMID- 2222944 TI - The initial vasodilation and the later vasoconstriction of endothelin-1 are selective to specific vascular beds. AB - The regional hemodynamic effects of endothelin-1 (ET-1) were studied in Wistar Kyoto rats. Endothelin-1 caused a transient increase in blood flow in the carotid and femoral arteries but a decrease in flow in the renal and mesenteric arteries. The resistance in the carotid and femoral beds decreased while it increased in the renal and mesenteric beds. Subsequently there was a variable increase in resistance in all vascular beds with a maximal increase in the renal bed. Thus, ET-1 initially causes a selective vasorelaxation in musculocutaneous beds but not in visceral beds; the cause of this selectivity is unknown. PMID- 2222945 TI - Renal and hemodynamic effects of endothelin in anesthetized dogs. AB - The effects of endothelin on systemic hemodynamics and renal functions were investigated in anesthetized dogs. Infusion of endothelin at a dose of 1 ng/kg/min decreased renal blood flow and increased renal vascular resistance and filtration fraction. Endothelin at doses higher than 10 ng/kg/min significantly decreased cardiac output, glomerular filtration rate, renal plasma flow, urine volume, and urinary sodium excretion. Mean arterial pressure showed a transient decrease at doses higher than 50 ng/kg/min. These results showed that endothelin in systemic administration has effects on renal functions as well as on systemic hemodynamics. PMID- 2222946 TI - What is blood pressure? PMID- 2222947 TI - Randomized trials in the study of antihypertensive drugs. AB - Heterogeneity in response to antihypertensive drugs can be addressed by randomized trials in individual subjects. In such a trial a patient receives pairs of treatment periods (one period of each pair active drug, one matched placebo, in random order); patient and clinician are blinded to allocation, and treatment targets are monitored. These trials can optimize antihypertensive therapy in clinical practice and facilitate the investigation of new drugs and the study of pathophysiology. Such trials also have potential in helping decide whether common, nonspecific symptoms reported by patients are really drug related. PMID- 2222948 TI - From the parallel group design to the crossover design, and from the group approach to the individual approach. AB - The consequences of heterogeneity in response to antihypertensive drugs for the clinical development programs of new antihypertensive drugs and for the care of the individual hypertensive patient have not previously been sufficiently recognized. They play a role in the inappropriate choice of too-high daily doses of some antihypertensive drugs at the end of extensive international development programs. They are also implicated in the insufficient control of blood pressure observed in the long-term multicenter trials in hypertension, where some patients have been treated for several years with drugs that were not the most appropriate for their disease and which did not adequately control their blood pressure. In addition to the parallel group studies, the use of double-blind two-period or multiple period crossover designs can provide valid data for the dose-finding of new antihypertensive drugs and their comparative evaluation. At the end of the trial, these designs also offer each patient the opportunity to be treated with the right dose of the drug most appropriate for his or her disease. PMID- 2222949 TI - Effect of captopril on renal function in hypertensive dogs with unilateral renal artery stenosis, studied with radionuclide dynamic scintigraphy. AB - The kidneys of five hypertensive dogs with experimental unilateral renal artery stenosis were examined by 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 131I-hippuran radionuclide dynamic scintigraphy at 10 and 40 min (respectively) following the administration of intravenous bolus injections of captopril. Doses of 0.2, 0.5, and 1.0 mg/kg captopril reduced mean arterial pressure by 33 +/- 4, 31 +/- 7, and 51 +/- 4 mm Hg and increased plasma renin activity by 40.1 +/- 9.8, 57.6 +/- 3.2, and 34.4 +/- 15.2 ng A1/mL/h, respectively. The time-activity curves of both 99mTc-DTPA and 131I-hippuran indicated that renal excretory function in the stenotic kidney was compromised with all three doses of captopril. However, if nitroprusside was used to reduce the mean arterial pressure to a level comparable to that with captopril, there was no appreciable increase in plasma renin activity and renal excretory function was only partially affected in the stenotic kidney. One hour after the administration of 0.5 mg/kg captopril, the function of the stenotic kidneys was partially restored and, by two hours, the time-activity curves were comparable to control scans. These data demonstrate a reversible, time-limited suppression of stenotic kidney function by captopril in renovascular hypertension and provide support for the use of captopril in the diagnosis of renovascular hypertension by radionuclide dynamic scintigraphy. PMID- 2222950 TI - Nonpeptide angiotensin II receptor antagonists. AB - Although the most direct way to interfere with the renin-angiotensin system (RAS) is at the level of the angiotensin II (AII) receptor, the currently available AII receptor antagonists are peptides still retaining significant agonistic properties with the obvious drawbacks of limited stability and lack of oral activity. We have characterized simple N-benzylimidazoles as weak, but selective AII receptor antagonists with a competitive mode of action. Chemical modification of these early leads led to EXP6155 and EXP6803, which show approximately 10- and 100-fold higher affinity. Oral activity was obtained for EXP7711, and in particular for EXP9654. This class of compounds displaces 3H-AII from its specific binding sites in various tissues. They competitively antagonize AII induced responses in various in vitro and in vivo preparations, but do not influence AII-induced responses to KCl, norepinephrine, and vasopressin, nor do they affect converting enzyme or renin. In high renin models of elevated blood pressure, such as the renal hypertensive rat and sodium-depleted dog, these substances produce a sustained decrease in arterial pressure without changing heart rate after intravenous and oral (EXP7711 and EXP9654) administration. None of these compounds showed agonistic activity in any of the above test systems. In conclusion, the nonpeptide structures described herein are selective and competitive AII receptor antagonists and add another dimension to the arsenal of drugs manipulating the RAS. PMID- 2222951 TI - Humoral factors determining the blood pressure response to converting enzyme inhibition and calcium channel blockade. AB - Renin and catecholamine levels were determined in patients with mild to moderate hypertension before and after treatment with sustained release diltiazem or captopril and were correlated with the blood pressure response to these antihypertensives. Eight weeks of treatment with either agent led to equal decreases in both systolic and diastolic blood pressure. Pretreatment plasma renin activity (PRA) and plasma norepinephrine did not predict the blood pressure response to either agent. Diltiazem significantly increased both PRA and supine norepinephrine levels. However, in the diltiazem treated patients, there was no correlation between the change in plasma norepinephrine and the change in systolic or diastolic blood pressure. In contrast, there was a negative correlation (P less than .05) between the reactive rise in PRA and the decrease in systolic blood pressure. Thus, the antihypertensive response to a calcium channel blocker may be determined, in part, by the reactive response of pressor systems. PMID- 2222952 TI - Effects of felodipine on urinary albumin excretion and metabolic control in hypertensive non-insulin-dependent diabetics. AB - The effect of a blood pressure reduction by 10 mg extended release felodipine once daily on urinary albumin excretion (UAE) as well as the possible diabetogenic effect of felodipine was studied. A 2 X 12 week placebo-controlled double-blind crossover study was performed in 12 hypertensive non-insulin dependent diabetic (NIDDM) patients without nephropathy on concomitant treatment with beta-blocker and/or a diuretic agent. Metabolic control as estimated by fasting plasma glucose, hemoglobin A1c and fasting plasma C-peptide was unaltered after felodipine. Blood pressure was significantly reduced by felodipine: systolic 166 +/- 26 mm Hg (placebo) v 153 +/- 26 mm Hg (felodipine) (P less than .05) and diastolic 95 +/- 7 mm Hg v 90 +/- 8 mm Hg (P less than .05). Heart rate was unchanged. There was no correlation between blood pressure and UAE, but the relative change in UAE expressed as UAE placebo/UAE felodipine was significantly correlated to the fall in systolic blood pressure (r = 0.64, P = .03) and mean blood pressure (r = 0.66, P = .02). Since microalbuminuria predicts proteinuria and reduced survival, early antihypertensive treatment may be beneficial in NIDDM as it is in IDDM. Long-term consequences on kidney function and mortality remains, however, to be elucidated. PMID- 2222953 TI - Platelet norepinephrine and epinephrine concentration in patients with pheochromocytoma. AB - Platelet and plasma catecholamine concentrations were determined in 17 patients with surgically proven pheochromocytoma (mean age 42.3 years); in 31 patients with borderline hypertension (mean age 35.3 years) and in 9 healthy controls (mean age 39.3 years). Both platelet norepinephrine and epinephrine were significantly increased in patients with pheochromocytoma when compared with hypertensive and control groups (P less than .001). No correlation between platelet and plasma catecholamines was detected in all studied groups. The diagnostic accuracy of platelet catecholamine in pheochromocytoma is limited since increased platelet norepinephrine was found in 35.5% and increased platelet epinephrine was found in 19.4% of patients with essential hypertension. PMID- 2222954 TI - Normalization of increased sodium sensitivity by maintenance hemodialysis. AB - Blood pressure (BP) becomes more sodium and body fluid sensitive as renal function deteriorates. Thus, hypertension in chronic renal failure is mostly of the sodium sensitive type. We studied whether the increased sodium sensitivity (SS) can be restored to normal on the maintenance phase of hemodialysis (HD) therapy. Body weight (BW) and BP (specifically, mean arterial pressure [MAP]) were measured after HD and before the next HD, and the body fluid sensitivity (BFS) was calculated as the ratio of changes in these factors on both introduction and maintenance phases in HD patients (n = 56) who were not taking any antihypertensive drugs (BFS = delta MAP/delta BW). In a preliminary study, the amount of interdialytic sodium intake (QNa+) was measured (n = 30), and SS was calculated as the ratio of the change in MAP to QNa+ (SS = delta MAP/QNa+). Interdialytic BW gain (3.1 +/- 0.1 kg) was correlated with the amount of sodium intake (136 +/- 17 mEq), resulting in a positive relationship between BFS and SS (r = 0.79, P less than .0001). Therefore, BFS was used as an index of SS. As a whole, BFS decreased from the introduction to the maintenance phase (6.5 +/- 1.0 to 3.5 +/- 0.6 mm Hg/L, P less than .01). This decrease was marked (6.2 +/- 1.1 to 2.9 +/- 0.6 mm Hg/L, P less than .01) in patients (n = 46) whose BP was normalized in the maintenance phase, while not significant (7.9 +/- 1.9 to 6.3 +/ 1.3 mm Hg/L) in patients (n = 10) whose BP was still high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222956 TI - Chronic effects of synthetic endothelin on blood pressure and sodium excretion in rats. AB - Continuous infusion of endothelin at a rate of 60 micrograms/kg/day into the jugular vein of rats via osmotic minipumps induced a significant increase in systolic blood pressure, but did not induce any significant changes in urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. When 6 mg/kg/day of benidipine, a newly developed calcium channel blocker, was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure of conscious rats rose on Day 1 to only 137.0 +/- 2.4 mm Hg (P less than .05) compared to the rise to 163.8 +/- 4.7 mm Hg when endothelin alone was infused. The antihypertensive effect of benidipine was sustained. The present results suggest that endothelin can act as a circulating hormone. In addition, they clearly demonstrate that the calcium channel blocker attenuates the elevation of blood pressure induced by endothelin. PMID- 2222955 TI - Effects of endothelin on renal hemodynamics and renal function in anesthetized dogs. AB - Porcine endothelin was infused directly into the renal artery of anesthetized dogs to evaluate the renal action of endothelin. Endothelin (0.2 to 5.0 ng/kg/min) elicited a dose-dependent reduction in the renal blood blow with no changes in systemic blood pressure. Endothelin infusion (0.2 ng/kg/min) decreased the renal blood flow by 30% and urinary sodium excretion by 50% without any changes in the glomerular filtration rate. However, higher doses did reduce glomerular filtration rate. These data suggest that endothelin preferentially constricts efferent arterioles and that endothelin may enhance the renal reabsorption of sodium. PMID- 2222957 TI - Alarm reaction and serum K+ in hypertensive patients. AB - The effect of serum K+ of the alarm reaction induced by the participation to an experimental noninvasive study was evaluated in 35 subjects with borderline hypertension and in 18 essential hypertensives. A group of 44 inpatients undergoing routine blood sampling served as a control. Serum K+, blood pressure and heart rate were measured before (casual) and after (baseline) 20 min of rest in the recumbent position. Baseline serum K+ values were significantly higher than casual values in patients participating to the experimental protocol while no change was observed in inpatients undergoing routine blood sampling. The increase in serum K+ induced by relaxation was significantly related to heart rate decrease (r = 0.73). After relaxation 75% of patients had an increase in serum K+ with a change greater than 10% in about 35% of patients. In a subgroup of patients who repeated the same test three times, the alarm reaction was still evident and not reproducible within each patient. These data suggest that when potassium levels are measured in outpatients undergoing diagnostic or experimental procedures falsely reduced levels can be found in a large proportion of subjects. PMID- 2222958 TI - Studies of salt intake in hypertension. What can epidemiology teach us? AB - It has been suggested that small changes in population blood pressure will have a major impact upon the incidence of cardiovascular disease caused by blood pressure elevation. Early reports indicated a close correlation between intercultural differences in salt intake and blood pressure. Before such epidemiological associations can be translated into population advice, certain conditions have to be met. The association has to be validated scientifically, and persuasive evidence has to be produced that the relationship is causal and reversible by changes in salt intake. Further, risk-benefit analysis should indicate that net harm is unlikely. Finally it has to be demonstrated that the population measures being advocated will produce an adequate change in dietary salt intake. The small individual effects upon blood pressure being examined, and the prevailing changes in blood pressure and cardiovascular mortality suggest that data will always fall short of the ideal and therefore that extrapolation will always be necessary. Nevertheless, a review of the present evidence indicates the inadequacies of the available data as a basis for population advice. PMID- 2222959 TI - Risks associated with dietary sodium reduction in the spontaneous hypertensive rat model of hypertension. AB - Sodium balance is maintained by a complex set up of hemodynamic, hormonal and neural mechanisms that affect intake, reabsorption and excretion. The focus of the following research was on the cardiovascular and neuroeffector effects of dietary Na reduction primarily in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) raised from 4 to 15 weeks on a control Na diet (CNa: 12 mmol per 100 g food) or various low Na diets (LNa: 0.5 to 3 mmol per 100 g food). With regards to hemodynamics and volume regulation, the lowest Na diet reduced blood pressure 15% and raised resting heart rate (20%) in SHRs but not WKYs. Blood volume, hematocrit, plasma electrolytes, extracellular volume, and cardiac output were not different between diets or strains. However, both LNa strains were abnormally sensitive to blood loss and showed attenuated pressor responses to both acute and chronic stress situations. Cardiac function was not altered by LNa treatment in either rat strain although structural compensations occurred. LNa treatment significantly attenuated the pressor reduction in mesenteric blood flow during stress which was primarily due to reduction in noradrenergic transmitter release and not due to altered receptor sensitivity, density, or Na/K ATPase activity. Compensatory sympathetic activity was increased as was sodium conservation through humoral mechanisms which maintained homeostasis. However, further neurohumoral compensation was markedly reduced. The data suggests that the hygienic sodium intake in humans should be experimentally defined before generalized measures are taken to reduced dietary sodium use throughout society. PMID- 2222960 TI - Blood pressure response to dietary calcium intervention in humans. AB - Epidemiological and experimental studies have suggested that dietary calcium deficiency may lead to the development of hypertension. This article reviews findings in human trials on calcium intervention with special reference to the responses of blood pressure and biochemical variables. Calcium supplementation consistently resulted in decreased blood pressure in a subset of hypertensive and normotensive subjects, but led to increased blood pressure in some hypertensive patients. The variable blood pressure responses to calcium supplementation could not be predicted on the basis of routine biochemical parameters and appeared to be due to differences in the backgrounds of the subjects and/or the design and size of the trials. It is concluded that further studies are required on the hypotensive effect of calcium supplementation. PMID- 2222961 TI - Sodium-calcium interactions and salt-sensitive hypertension. AB - In humans with essential hypertension, salt-induced increases in blood pressure have been reported to correlate directly with salt-induced increases in intracellular free calcium [( Ca2+]i) in circulating mononuclear cells. These findings are consistent with the hypothesis that salt-induced increases in [Ca2+]i mediate the phenomenon of salt sensitivity. Circumstantial evidence suggests that salt-induced increases in intracellular sodium or in plasma levels of 1,25-dihydroxy vitamin D might mediate salt-induced increases in [Ca2+]i and blood pressure. However, in humans with salt-sensitive hypertension, it remains to be determined: (1) whether salt-induced increases in white blood cell [Ca2+]i reflect corresponding increases in vascular smooth muscle [Ca2+]i; (2) whether salt-induced increases in [Ca2+]i are a cause or consequence of salt-induced increases in blood pressure; and (3) whether salt-induced increases in 1,25 dihydroxy vitamin D or intracellular sodium precede salt-induced increases in [Ca2+]i. PMID- 2222962 TI - Putative mechanism of blood pressure reduction induced by increases in dietary calcium intake. AB - An increase in dietary calcium intake lowers blood pressure in spontaneously hypertensive rats and in some patients with arterial hypertension. The mechanisms by which this decrease come about are not clear. A membrane-stabilizing effect wrought by an increase in extracellular calcium would appear unlikely, since the increases in extracellular calcium concentration with increased dietary intake are minimal. Calcium regulatory hormones may be the mediators, and a cybernetic framework has been suggested. Striking defects have been reported in the calcium handling and hormonal household of the spontaneously hypertensive rat. However, a clear cut relationship in terms of a hormonal "template" has not yet been identified in prospective experiments. Data have been presented to show that increased calcium intake has a direct effect on regulatory areas in the brain. However, the mechanisms by which such a response would be mediated are entirely unknown. Increased calcium intake may induce natriuresis. It has been suggested that increased calcium intake helps the "salt sensitive"; however, prospective studies to this effect have not been presented. Increased calcium intake may induce phosphaturia. However, the evidence that blood pressure lowering effects are mediated by phosphate depletion are unconvincing. Some evidence suggests that increased calcium intake may influence local regulatory processes which in turn influences cell integrity and growth. At this point, a unifying hypothesis is not available. However, the clues to various possibilities are intriguing. PMID- 2222963 TI - Calcium regulating hormones in essential hypertension. Importance of gender. AB - Alterations of calcium metabolism have been described in human essential hypertension and experimental hypertension. We investigated the interrelationship of parathyroid hormone (PTH) and 1,25(OH)2-vitamin D (1,25(OH)2D) in patients with untreated essential hypertension as compared to normotensive controls. The hypertensive subjects (n = 75; 43 men, 32 women) had a mean blood pressure of 138 +/- 8/95 +/- 5 mm Hg as compared with 120 +/- 11/80 +/- 8 in the normotensive group (n = 40; 22 men, 18 women). Serum PTH was measured with an intact molecule immunochemiluminometric assay and 1,25(OH)2D was measured with radioimmunoassay after HPLC separation. Hypertensive men had PTH levels that were 36% higher than normotensive men (5.3 +/- 2.9 v 3.9 +/- 0.8 pmol/L, P = .005). When blood pressure was analyzed as a continuous variable, there was a direct correlation between it and serum PTH in men (r = .31, P = .004). In women, by contrast, there was no difference in serum PTH between hypertensive and normotensive subjects and no relationship between blood pressure and the serum PTH concentration. Blood pressure was inversely correlated with serum phosphorus levels in both sexes (r = -0.20, P = .04). In men, the elevated serum PTH levels and depressed serum phosphorus levels would have predicted that serum 1,25(OH)2D would be higher in the hypertensive subjects. However, that was not observed, as serum 1,25(OH)2D was slightly lower in hypertensive (38.3 +/- 15.2 pg/mL) than normotensive men (42.7 +/- 11.3, P = .21).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222964 TI - Calcium, parathyroid hormone, and vitamin D in the "prehypertensive" Dahl salt sensitive rat. AB - The purpose of this study was to determine if alterations of calcium and calcium regulating hormones precede the onset of NaCl-induced hypertension in the Dahl salt-sensitive (S) rat. After a 5-day balance study, serum ionized calcium, parathyroid hormone (PTH), and 1,25-dihydroxy vitamin D concentrations were measured in Dahl-S and salt-resistant (R) rats that had been maintained on a "normal" (1%) or high (7%) NaCl intake. Blood pressure was higher in Dahl-S than Dahl-R (P less than .01), but was not affected by 5 days of high NaCl. On both NaCl intakes, urine calcium excretion was increased, serum calcium was decreased, and serum PTH and 1,25 dihydroxy vitamin D were increased in Dahl-S compared to Dahl-R (P less than .01). On the high NaCl intake, fecal calcium was greater in Dahl-S than in Dahl-R, and net 5-day calcium balance was less positive in Dahl-S (P less than .05). Thus, alterations of calcium, PTH, and vitamin D precede NaCl induced hypertension in Dahl-S. These alterations may contribute to the development of hypertension in this animal model. PMID- 2222966 TI - Vascular and calcemic effects of plasma of spontaneously hypertensive rats. AB - Circulating substances that increase intracellular calcium, and other circulating substances that increase blood pressure, have been described in hypertensive animals and humans. In this study, we report the existence of a factor of the plasma of spontaneously hypertensive rats that does both. These effects were dose dependent, and the time course for such effects was correlated with the time course for potentiation of pressor agents by the plasma. In addition, the plasma of spontaneously hypertensive rats was found to inhibit the depressor effects of parathyroid hormone. Our results confirm the presence of a circulating hypertensive factor in the plasma of spontaneously hypertensive rats, which may act by increasing calcium uptake in vascular smooth muscle. These findings may also help explain the secondary increase in parathyroid hormone noted in some forms of human and experimental hypertension. PMID- 2222965 TI - Calciotropic hormones in human and experimental hypertension. AB - Although altered cellular calcium handling plays a critical role in the pathophysiology of hypertension, little attention has been focused on the impact of calcium regulating hormones on this process. Recent research provides evidence that parathyroid hormone, calcitonin, 1,25-dihydroxyvitamin D, as well as newly described factors such as calcitonin gene-related peptide (CGRP), exert target organ-specific actions in cardiac and peripheral vascular tissues, are linked to the renin-aldosterone system, and thus to the control of sodium metabolism, and may directly participate in the hypertensive process, especially in low renin and salt sensitive forms of hypertensive disease. The metabolic set-point of these linked renin and calcium hormone systems, which serve to transduce environmental dietary mineral signals at the cellular level, determines the blood pressure consequences of sodium and calcium loading and/or restriction, and helps to explain the heterogeneous and seemingly inconsistent effects of these dietary maneuvers on blood pressure. Measurement of renin and calcium factors in hypertension thus provides a physiological basis for individualized therapeutic recommendations in human hypertension. PMID- 2222968 TI - Possible mechanisms of abnormal norepinephrine sensitivity and reactivity of resistance vessels and the development of hypertension in spontaneously hypertensive rats. A hypothesis. AB - This study examined structural and functional changes of mesenteric resistance vessels in early, developing, and established stages of hypertension development in spontaneously hypertensive rats in an attempt to identify possible mechanisms of the development and maintenance of hypertension. Our results suggest that the development of hypertension in spontaneously hypertensive rats may be caused by genetic structural and functional abnormalities of resistance vessels. Both abnormalities may be caused by hyperreactivity to norepinephrine through an altered signal transduction process, including the regulation of protein kinase C in smooth muscle cells of resistance vessels in spontaneously hypertensive rats. PMID- 2222967 TI - Epithelial abnormalities in intestine and kidney of the spontaneously hypertensive rat. AB - A variety of perturbations of calcium metabolism are reported to occur in the spontaneously hypertensive rat (SHR) compared to its genetic control the Wistar Kyoto rat (WKY), including significant dysfunction of calcium handling by the proximal renal tubule of the SHR, resulting in impaired active calcium transport in the gut and an apparent renal calcium leak. We explored the intestinal and renal epithelia of 12- to 14-week-old SHR and WKY using electron microscopy. Biochemical comparisons of these transport epithelia included measurements of three vitamin D dependent cellular proteins and one structural protein: alkaline phosphatase, intestinal CaBP9K, renal CaBP28K, and villin expression. Electron microscopy demonstrated a patchy loss in microvilli in the SHR, accounting for approximately 10 to 15% of the total microvillar surface. In the kidney, morphological abnormalities were observed only in the proximal renal tubule. Again, there was patchy loss of microvilli from the brush border membrane. In SHR duodenal alkaline phosphatase activity was significantly reduced compared to the WKY (0.145 +/- 0.002 v 0.186 +/- 0.002 integrated extinction/min/micron 3 X 10(3) brush border (P less than .001). Duodenal CaBP9K and renal CaBP28K were significantly reduced in SHR compared to WKY. There were no differences in villin expression. These data are consistent with the previously characterized disturbances of active calcium transport in the intestine and inappropriate renal calcium leak in the SHR. While a possible link between these disturbances and hypertension remains to be determined, this study provides supportive evidence for a primary disturbance in cell calcium handling and transporting epithelia in this form of genetic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222970 TI - Increase of calmodulin activator in hypertension. Modulation by dietary sodium and calcium. AB - The aim of this study was to investigate the effects of dietary calcium and sodium on blood pressure (BP) in normotensive rats (Wistar, WKY), spontaneously hypertensive rats (SHR) and Dahl rats and on calmodulin (CaM) activator, a newly discovered hydrophobic compound that increases CaM activity in SHR and spontaneously hypertensive mice (SHM) tissues (J Clin Invest 82:276, 1988). The CaM activator was assessed by its capacity to stimulate a CaM-dependent phosphodiesterase (CaM-PDE). In Wistar rats, which were fed a high sodium diet (3.5%), BP significantly increased (P less than .01) from 106 +/- 4 to 128 +/- 8 mm Hg in parallel to an elevation of the CaM activator from 1.57 +/- 0.14 to 2.80 +/- 0.18 U. WKY, SHR, and Dahl salt-sensitive (DS/JR) and salt-resistant (DR/JR) rats were given low (0.15%) or high (2.5%) Ca diets, both with 1% sodium. In rats receiving high dietary Ca the progression of hypertension diminished and BP was lower in SHR (156 +/- 4 mm Hg) and young DS/JR rats (125 +/- 3 mm Hg) than in those receiving low dietary Ca (192 +/- 10 and 183 +/- 2 mm Hg). There was a concomitant decrease of CaM activator in these animals to levels indistinguishable from those of WKY or DR/JR rats. The activator was also found in the heart, kidneys and erythrocytes from SHM. In the presence of exogenously added CaM, lipidic extracts from the SHM heart showed augmented CaM-PDE activity relative to normotensive preparations. This difference was eliminated by trifluoperazine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222969 TI - Contribution of calmodulin and protein kinase C to renin release in spontaneously hypertensive rats. AB - This study was designed to evaluate the contribution of calmodulin and protein kinase C to renin release from isolated glomeruli of spontaneously hypertensive rats (SHR, Okamoto and Aoki). Male 7-week-old SHR and age-matched control Wistar Kyoto rats (WKY) were used in this study. Isolated glomeruli were sealed in the superfusion chamber and perfused with Krebs-Ringer solution at a constant flow of 0.3 mL/min. Renin release was increased by calmodulin inhibitor, W-7, and protein kinase C inhibitor, H-7, in both SHR and WKY. SHR showed higher maximal levels of renin release by W-7 and lower maximal levels by H-7 compared to WKY. These results indicate that calmodulin and protein kinase C play inhibitory roles in renin release from juxtaglomerular cells. The calmodulin-mediated suppression mechanism in renin release appears to be augmented in the SHR, whereas the protein kinase C-mediated system is attenuated. PMID- 2222971 TI - Roles of protein kinase C on the mechanical activity of vascular smooth muscles. AB - We investigated the role of protein kinase C in the mechanical responses evoked by high K or by acetylcholine (ACh) in intact vascular smooth muscle tissues, and by Ca in skinned vascular smooth muscle tissues. To activate protein kinase C, the phorbol ester 12-o-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter, or 1,2-diolein, plus phosphatidylserine (PS) was used. TPA enhanced or reduced the amplitude of the contraction evoked by increased concentrations of K below 39 mmol/L or over 90 mmol/L, respectively, but consistently enhanced the resting tension at any given concentration of high K. Similar effects of TPA were observed on the Ca-induced contraction in saponin skinned muscle tissues. The enhancing action of TPA on the K-induced contraction was not related to activation of either the voltage-dependent Ca channel or the sarcoplasmic reticulum, and did not occur in the case of Ca-independent contraction in skinned muscle tissues. During the enhancement of the contraction induced by TPA, the phosphorylation of myosin light chain and the shortening velocity of contraction as measured using the slack test, were enhanced with no remarkable change in the free Ca concentration in the cytosol. TPA consistently inhibited the ACH-induced contraction accompanied by a marked reduction in free Ca due to inhibition of the hydrolysis of phosphatidyl inositol 4,5-bisphosphate. Under the assumption that TPA possesses the same action as DG, activation of protein kinase C increased the Ca sensitivity of contractile proteins in vascular smooth muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222972 TI - Responses of cytosolic free calcium to ADP in platelets of spontaneously hypertensive rats. AB - Abnormalities of Ca2+ handling have been reported in patients with essential hypertension and in spontaneously hypertensive rats (SHR). In this study, responses of cytosolic Ca2+ to ADP in platelets of SHR were examined. Four- and seven-week-old male SHR and age- and sex-matched Wistar-Kyoto rats (WKY) were used. Basal levels of the intracellular Ca2+ concentration in platelets and responses to ADP were estimated using fluorescent indicator fura-2 in the medium containing 1 mmol/L CaCl2 and Ca2(+)-free buffer with 1 mmol/L EGTA. Basal levels of platelet cytosolic Ca2+ of SHR were significantly higher than those of WKY at 4 and 7 weeks of age in the presence of external Ca2+. However, no significant difference was observed in basal levels of platelet cytosolic Ca2+ in the Ca2(+) free EGTA-containing buffer between SHR and WKY. The peak cytosolic Ca2+ concentration evoked by ADP was significantly diminished in SHR compared with WKY in the absence of external Ca2+, whereas the responses of platelet cytosolic Ca2+ to ADP were similar in SHR and WKY in the presence of external Ca2+. These results suggest that release from intracellular Ca2+ store is reduced in SHR and that the regulation of cytosolic Ca2+ in SHR is more dependent on extracellular Ca2+ compared with WKY. PMID- 2222973 TI - The cellular mechanism of action by vasoconstrictor hormones in cultured rat vascular smooth muscle cells. AB - The effects of angiotensin (Ang) II, arginine vasopressin (AVP), and serotonin (5 HT) on inositol trisphosphate (IP3) production, cytosolic Ca2+ concentration [( Ca2+]i), and the phosphorylation of 20 kilodalton myosin light chain (MLC) were examined in cultured rat vascular smooth muscle cells (VSMC). These vasoconstrictors immediately induced dose-dependent and concomitant increases in IP3 production, [Ca2+]i, and phosphorylation of 20 kDa MLC. The agonist-induced increases in IP3 production, [Ca2+]i, and phosphorylation of 20 kDa MLC in VSMC were completely blocked by pretreatment with the receptor antagonists for Ang II, V1, and 5-HT2, respectively. These data suggest that receptor-mediated increases in IP3 production, [Ca2+]i, and phosphorylation of 20 kDa MLC by these vasoconstrictors are closely interrelated. PMID- 2222974 TI - Molecular pharmacology of calcium, calmodulin-dependent myosin phosphorylation in vascular smooth muscle. AB - The Ca2+, calmodulin (CaM)-dependent phosphorylation of the 20 kDa myosin light chain (LC20) is accepted as an important component of the regulatory mechanism in smooth muscle contraction. Since we have originally developed selective inhibitors of each process of the intracellular Ca2+ messenger system, the effect of a newly synthesized compound ML-9, a myosin light chain kinase (MLCK) inhibitor on superprecipitation of actomyosin, isometric tension development and phosphorylation of LC20 in vascular smooth muscle was investigated. Superprecipitation of actomyosin from bovine aorta was inhibited by the addition of ML-9 in a dose-dependent manner. In chemically skinned smooth muscle cells of the rabbit mesenteric artery, ML-9 inhibited both Ca2+ and Ca2+, CaM-independent MLCK-induced contraction. In the intact vascular strips, increase in LC20 phosphorylation reached a maximal value within 10 sec from a resting value, and then declined to near the basal level during the maintained isometric force developed in response to 50 mmol/L KCl. Both the maximal rate and extent of KCl induced contraction and the phosphorylation of LC20 were also inhibited by ML-9. It antagonized the contraction induced by various contractile agonists, such as NE, 5HT, His, and Ang II concomitant with the inhibition of LC20 phosphorylation. These results suggest that ML-9 inhibits the actin-myosin interaction through the modulation of LC20 phosphorylation via the inhibition of MLCK activity. ML-9 will aid in determining pathophysiological functions of MLCK of increased vascular contractility in hypertension. PMID- 2222975 TI - Parathyroid hormone and the vascular response to norepinephrine. AB - Norepinephrine blood pressure reactivity is reduced in uremia, an effect attributed to excess parathyroid hormone (PTH). Most, but not all, animal and human studies support the theory that high PTH levels diminish the pressor response to norepinephrine. In hemodialysis patients in whom norepinephrine infusion tests were performed to determine the effect of parathyroidectomy on vascular responsiveness, the vascular response to norepinephrine (100 ng/kg/min) improved significantly (11.3 +/- 1.3 mm Hg before and 17.5 +/- 2.4 mm Hg after parathyroidectomy; P less than .01). Excess parathyroid hormone appears to play an active role in reduced vascular responsiveness to norepinephrine, although the mechanisms of this effect are unknown. PMID- 2222977 TI - Echocardiographic measurement of left ventricular mass and volume in normotensive and hypertensive rats. Necropsy validation. AB - Although rats are commonly used to study left ventricular (LV) hypertrophy, measurement of LV mass and dimensions has required killing the rat. To determine the accuracy of echocardiography in rats, blinded crossectional area (CSA) and LV mass measurements using either the cube function (LVM) or an elliptical model (LVMel) from high resolution M-mode echocardiograms were compared to necropsy LV weight (0.28 to 1.5 g), in 41 normotensive (body weight 116 to 762 g) and 17 hypertensive rats (350 to 560 g). Postmortem chamber volumes in 28 normal rats (0.02 to 0.19 mL) were also compared to echocardiographic volumes derived from the elliptical model. Correlation with LV weight was r = 0.87 for LVM, 0.90 for CSA and 0.93 for LVMel (all P less than .00001). Comparison of hypertensive and body-weight-matched normotensive rats revealed the upper normal limit for both LVMel and CSA to have 89% sensitivity and 100% specificity for detection of post mortem LV hypertrophy. Necropsy LV volumes were more closely related to systolic echocardiographic volumes than to diastolic volumes (r = 0.78 v 0.71, both P less than .00001), compatible with the effects of post mortem contracture. Stroke volume determined invasively in 5 Wistar rats by thermodilution was similar to that obtained using elliptical model echo volumes in 5 rats of the same body size (0.35 +/- 0.05 v 0.30 +/- 0.06 mL/beat). Echocardiography can be used to evaluate LV structure and function in rats and to detect in vivo LV anatomic differences induced by hypertension. PMID- 2222976 TI - Effects of prostaglandin F2 alpha on the mobilization of cytosolic free calcium in vascular smooth muscle cells and on the tension of aortic strips from rats. AB - The possible mechanism of action of prostaglandin F2 alpha on vascular smooth muscle was investigated. Prostaglandin F2 alpha induced sustained tonic vasoconstriction of rat aortic strips, accompanied by rapid increase in the cytosolic free Ca2+ concentration [( Ca2+]i) in the vascular smooth muscle cells. Prostaglandin F2 alpha also evoked rapid increase in production of inositol 1,4,5,-trisphosphate (Ins-P3). Moreover, it increased release of Ca2+ from nonmitochondrial pools in digitonin-permeabilized vascular smooth muscle cells, although this effect was much weaker than that of Ins-P3. These results suggest that the sustained action of prostaglandin F2 alpha may involve not only a rise in [Ca2+]i mediated by Ins-P3, but also a direct stimulation of Ca2+ from intracellular stores. PMID- 2222978 TI - The reliability of auscultatory measurement of arterial blood pressure. A comparison of the standard and a new methodology. AB - In 48 individuals with a wide range of arm circumferences blood pressure measured indirectly with two different cuffs was compared to direct intraarterial measurements. The two cuffs were a standard size cuff (12 X 35 cm) and a newly developed cuff, containing three rubber bags of different sizes, which automatically selects the appropriately sized bag in relation to arm circumference (Tricuff, Pressure Group AB, Sweden). The Tricuff correctly placed 42 of the 43 patients in the "normotensive" range, ie, diastolic blood pressure less than 90 mm Hg, whereas the standard cuff put only 33 of 44 patients in this range (P less than .005). The discrepancy was not only due to the expected better performance in patients with obese arms, but also in the subgroup of patients with arms in the range 22 to 31 cm, in which group both cuffs would measure blood pressure with a 12 cm wide rubber bag. The number of correctly identified "normotensive" patients was noticeably higher with the Tricuff than with the standard cuff (30/31 v 25/32, P = .053). The better specificity of the new cuff thus offers an improvement over the standard cuff. There are several potential clinical advantages of this, mainly that the risk of erroneously labelling normotensive individuals as hypertensive is reduced. PMID- 2222979 TI - A validation study of the instromedix Baro-Graf QD home blood pressure monitor. AB - The purpose of this study was to assess the accuracy of the Instromedix Baro-Graf QD home blood pressure monitor. Forty subjects were divided among three blood pressure (BP) groups: low (BP less than 110/70, N = 11); medium (BP 110/70 to 140/90, N = 17) and high (BP greater than 140/90, N = 12). Five seated readings were taken per subject. We examined the differences between simultaneous auscultatory and machine readings and assessed the machine's accuracy using ANOVA and correlation analysis. The results show that the device, while highly accurate, tended to become less so as pressure increased. However, its accuracy was superior compared to most other devices we have tested, and because of features, such as a computer memory that stores events and blood pressure over time, this monitor will likely be a useful tool for clinical trials of long term blood pressure change. PMID- 2222980 TI - Post-transplant hypertension. AB - Post-transplant hypertension remains an important risk factor for cardiovascular mortality and graft function. There are multiple mechanisms responsible for post transplant hypertension. The details of these mechanisms are poorly understood. Steroids, acute and chronic rejection, recurrent renal disease, native kidney disease, and renal artery stenosis have all been implicated in causing post transplant hypertension. With the addition of cyclosporine, a known hypertensive agent, to the immunosuppressive armamentarium, the evaluation of post transplantation hypertension has become difficult. Presently, medical therapy is initially directed toward the complications of cyclosporine nephrotoxicity. Empirically, converting enzyme inhibitors are added to the antihypertensive regimen. Further management is aimed at identification of specific causes of post transplant hypertension. Unfortunately, because of the multifactorial etiology of post-transplant hypertension and a lack of detailed information about the mechanisms, medical and surgical therapy are often unrewarding. Further study is needed to clarify the mechanisms involved in post-transplant hypertension, and thus direct therapy. PMID- 2222982 TI - Pain as an addiction (some people simply must have it!) PMID- 2222981 TI - How far should blood pressure be lowered? What is the role of the J-curve? PMID- 2222983 TI - The alien hand sign. Localization, lateralization and recovery. AB - The alien hand sign was first described by Brion and Jedynak as a "feeling of estrangement between the patient and one of his hands." The affected hand frequently shows a grasp reflex and an instinctive grasp reaction as well as elements of what Denny-Brown referred to as a "magnetic apraxia" associated with frontal lobe damage. Most notably, however, the affected hand is observed to perform apparently purposive behaviors that are perceived as being outside the volitional control of the patient. The patients interpret the behavior of their own affected limb as being controlled by an external agent. They do not feel that they are initiating or controlling the behavior of the hand and often express dismay at the hand's "extravolitional" activity. The patients attempt to control behavior of the alien hand with the unimpaired hand by forcibly restraining the affected limb, an act that may be termed "self-restriction." In this paper, we report an additional four cases of alien hand sign in right-handed subjects: two involving the right hand and two involving the left hand. In each case, the clinical findings were associated with extensive unilateral damage of the medial frontal cortex of the hemisphere contralateral to the affected hand. Furthermore, the alien movement gradually disappears over the course of 6-12 months after the stroke. These clinical case studies are presented and discussed in the context of the "dual premotoer systems hypothesis," an anatomicophysiological model that proposes that action is organized by two separate but interactive premotor brain systems corresponding to evolutionarily defined medial and lateral cortical moieties. It is hypothesized that the alien mode behavior results from unconstrained activity of the lateral premotor system in the damaged hemisphere. The residual volitional control in the limb occurs through the activity of the intact medial premotor system of the ipsilateral hemisphere. Recovery may occur through extension of these ipsilateral control mechanisms by compensatory changes in subcortical systems controlling hemispheric activation associated with adaptive behavior. This observation may be important in understanding mechanisms involved in motor recovery after stroke. PMID- 2222984 TI - The effect of local deep microwave hyperthermia on experimental zymosan-induced arthritis in rabbits. AB - The effect of local deep microwave hyperthermia (LDMWH) on normal and Zymosan induced arthritis has been evaluated in 12 rabbits (24 joints). LDMWH, four treatments to each joint (twice weekly for a period of 2 wk), was generated by an antenna operating at 915 MHz for 60 min, reaching an intraarticular temperature of 42.5 +/- 0.5 degrees C. A surface cooling system was used with the microwave apparatus. Two weeks after the last treatment, all animals were sacrificed. The application of LDMWH on normal joints induced a limited proliferation of the synovial lining cells with a minimal perivascular infiltration of mononuclear and neutrophil cells. However, no histologic damage to the skin, muscles, bone, cartilage or bone marrow adjacent to the heated joints could be noted. Induction of Zymosan arthritis (2 wk before LDMWH) was characterized by pannus formation and granulomatous reaction accompanied by fibrinoid deposits and disseminated necrotic foci in the synovial intima. The LDMWH treatment on the examined arthritic joints brought about a reduction in the degree of granulomatous reaction concomitant with the appearance of some fibrocytes and fine collagen fibrils. These findings suggest that LDMWH can be safely applied, even repeatedly, without morphologic evidence of damage to any normal mesenchymal tissue. Moreover, it reduces the inflammatory process in experimentally induced synovitis. PMID- 2222985 TI - Cardiac arrhythmias from a malpositioned Greenfield filter in a traumatic quadriplegic. AB - A case study is presented of premature Greenfield filter discharge with intracardiac migration and resulting life-threatening arrhythmias. These arrhythmias also interfered with the patient's transition from ventilatory support via orotracheal intubation to noninvasive positive airway pressure ventilatory support methods. The patient's arrhythmias were controlled by a demand cardiac pacemaker and cardiac glycoside therapy. No anticoagulants were used. She had no further filter migration nor significant complications for 16 months after hospital discharge. PMID- 2222986 TI - The supraspinal anxiolytic effect of baclofen for spasticity reduction. AB - Recent studies in the psychiatric literature indicate that baclofen has an anxiolytic action in certain psychopathologic conditions. Clinical observation has shown that manifestations of spasticity are increased in anxious individuals, implicating a supraspinal site of mediation for these responses. The purposes of this study were to determine if baclofen reduced anxiety in individuals with traumatic spinal cord lesions and whether that reduction was correlated with decreased spasticity from the baclofen. Five adult males with traumatic spinal cord injury were randomly assigned to the study protocol. A double-blind, repeated measures, multiple base-line, single-case research design was employed. The independent variable was dose of medication with the three levels being placebo, 40 mg/day of baclofen and 80 mg/day of baclofen, in four evenly divided doses. The dependent variable was the score obtained on the Beck Inventory-A anxiety scale (BIA). The subjects were administered the BIA twice per week for a nine-week period of time, during which they received the doses of medication as described. Quantitative measurements of spasticity were also taken at each session. Visual inspection analysis of the data showed that two subjects had no measurable anxiety of the BIA throughout the study. Three subjects had measurable anxiety on the BIA during the base-line/placebo phase. They showed a decreased level of their BIA scores with 40 mg/day of baclofen, and a further level reduction with 80 mg/day of baclofen. The reduction in BIA scores was statistically significant using the standard deviation band test in one of these subjects. These data indicate that BIA probably has an anxiolytic effect for individuals status post-traumatic spinal cord injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2222987 TI - Educational survey. Common questions asked by medical students about physiatry. PMID- 2222988 TI - Research in physical medicine and rehabilitation X. Information resources. AB - Researchers in physical medicine and rehabilitation require access to information regarding possible interventions and programs, available services and technology, research (published, unpublished and in progress), statistics on incidence, prevalence and expected recovery, and funding sources. This paper provides an overview to the most readily available sources of information, including 16 abstracts and indexes, 6 sources of review articles, 9 population statistical databases and 84 journals specifically devoted to rehabilitation. Of these journals, 29 may be accessed through Medline and 32 through other sources. An additional 58 journals indexed in Medline publish more than 16 rehabilitation articles per year. The journals within Medline that publish the most rehabilitation articles are listed by topic area: geriatric rehabilitation, cardiac rehabilitation, pediatric rehabilitation, rehabilitation research, self help devices, sports medicine and rheumatologic rehabilitation. Specific search strategies that may be used for any computer assisted search of Medline are given to locate articles in these topic areas and also the following areas: amputee rehabilitation, spinal cord injury rehabilitation, traumatic brain injury rehabilitation, cerebral palsy rehabilitation, stroke rehabilitation, decubitus care, electrodiagnosis, rehabilitation engineering, pain rehabilitation, pulmonary rehabilitation, sexual rehabilitation and urologic rehabilitation. The user friendly Grateful Med software is introduced for simplified online Medline searching. Exercises are provided for starting a journal club with the retrieved articles. PMID- 2222989 TI - Pentobarbital inhibits extracellular release of dopamine in the ischemic striatum. AB - We examined whether pentobarbital (PB) inhibited the acute extracellular release of dopamine that occurs in the striatum following the onset of ischemic injury in the gerbil model of stroke. The cerebral dialysis technique was employed to monitor striatal extracellular dopamine concentrations before and after carotid artery occlusion while perfusing either a control solution of artificial cerebrospinal fluid (CSF) or a 1 mM solution of pentobarbital in CSF (PB/CSF). During perfusion with CSF, extracellular dopamine increased from a baseline concentration of 0.40 +/- 0.09 (SEM) pmoles/10 minute collection interval to 30.0 +/- 9.0 pmoles/10 minutes after carotid artery occlusion. In contrast, during perfusion with PB/CSF, dopamine levels increased from a baseline of 1.37 +/- 0.3 pmoles/10 minutes to 8.30 +/- 2.6 pmoles/10 minutes; this increase was significantly less than the increase in controls. In animals with established ischemia, repeatedly alternating the perfusion fluid between CSF and PB/CSF demonstrated that dopamine concentrations were significantly increased with CSF alone and decreased with PB/CSF. These findings demonstrate that pentobarbital perfusion either before or following the onset of ischemia inhibits extracellular release of dopamine in the striatum. Inhibition of neurotransmitter release may, in part, be responsible for the protective effect of pentobarbital in ischemic brain injury. PMID- 2222990 TI - Presynaptic effects of gamma-aminobutyric acid on norepinephrine release and uptake in rat pineal gland. AB - The effect of tau-aminobutyric acid (GABA) on pineal norepinephrine (NE) release was examined in vitro in the rat pineal gland. Exposure of pineal explants previously loaded with 3H-NE to 1-100 microM GABA caused a dose-dependent decrease of 3H-NE release triggered by 60 mM K+, with a threshold GABA concentration of 1 microM and IC50 of about 10 microM. The inhibitory effect of GABA was mimicked by the type B GABA agonist baclofen, displaying a similar dose response relationship as GABA. The type A GABA agonist muscimol increased depolarization-induced 3H-NE release, while the co-incubation with GABA and the type A receptor antagonist bicuculline augmented significantly GABA's depressive effect on 3H-NE release. Bicuculline alone brought about a significant decrease of 3H-NE release. Neither GABA, nor baclofen, muscimol or bicuculline, modified the spontaneous pineal 3H-NE efflux. Assessment of 3H-NE uptake at a low NE concentration (0.5 microM) indicated that GABA decreased it in a dose-dependent manner (IC50 = 100 microM) through an effect blocked by bicuculline and mimicked by muscimol but not by baclofen; at a 5 microM-3H-NE concentration a bicuculline sensitive GABA augmentation of uptake was found. A kinetic analysis study of the pineal NE uptake process indicated that GABA augmented both Vmax and Km of transmitter uptake. These results indicate that GABA may be a significant regulatory signal for rat pineal sympathetic synapses. PMID- 2222991 TI - Quantitative analysis of "synaptic" ribbon profiles in the pineal complex of male and female Pirbright-White guinea pigs. AB - Previous studies have pointed in the direction of sex differences as well as regional differences in the pineal gland of guinea pigs. In the present investigation these aspects were studied at the electron-microscopic level by quantitating different types of "synaptic" bodies, intrinsic to pinealocytes. The two major types of "synaptic" organelles, ribbons and spherules, did not exhibit regional or sex differences. "Synaptic" structures intermediate in appearance to ribbons and spherules were significantly larger in number in males in the distal region of the pineal gland, compared to females. As previous studies have shown that ribbon and spherule numbers undergo characteristic changes depending on the functional state of the pineal gland, it is concluded that, as far as the "synaptic" organelles are concerned, no clear-cut sex or regional differences appear to exist in the guinea pig pineal gland. PMID- 2222992 TI - Alterations in neocortical expression of nicotinic acetylcholine receptor mRNAs following unilateral lesions of the rat nucleus basalis magnocellularis. AB - We investigated the effect of a unilateral lesion of the nucleus basalis magnocellularis (nbm) on the expression of nicotinic acetylcholine receptors (nAChRs) in the rat cerebral cortex. Cortical nAChR concentration as determined by [3H]nicotine binding was unaffected by the nbm lesion. Expression levels of nAChR subunit mRNAs were measured using cDNA clones coding for the receptor subunits, alpha-3, alpha-4, and beta-2. At 1 week postlesion, expression levels of alpha-4, and beta-2 were increased by an average of 82% and 19%, respectively. On the other hand, expression levels of these mRNAs on the lesioned side 4 weeks after lesioning did not differ from those on the control side. Expression of alpha-3 was not altered by the nbm lesion. These results imply regulation of nAChR transcripts by cell to cell interactions. Co-increase of alpha-4 and beta-2 transcripts may provide supporting evidence for the occurrence of supersensitivity in deafferentated cholinergic neurons. PMID- 2222995 TI - A stalk-specific wheat germ agglutinin binding protein, wst34, in Dictyostelium discoideum can be detected with antiserum raised against Dictyostelium mucoroides stalk. AB - A new stalk-specific wheat germ agglutinin (WGA) binding protein, wst34, has been identified in Dictyostelium discoideum and purified by the use of preparative sodium dodecyl sulfate - polyacrylamide gel electrophoresis and a WGA-affinity column. In normal development, wst34 appears during culmination and is maintained in stalk cells. It has a molecular mass of 34 kilodaltons and a pI value of 5.5 6.5. A polyclonal antiserum raised against stalk cell proteins of Dictyostelium mucoroides recognizes wst34 in western blots of D. discoideum proteins. PMID- 2222994 TI - Biochemistry of natural freeze tolerance in animals: molecular adaptations and applications to cryopreservation. AB - For a wide variety of animals, winter survival in cold climates includes the ability to tolerate ice formation in extracellular body fluids. Among terrestrially hibernating vertebrates, freeze tolerance has been documented for five amphibian and two reptile species. These species may survive for days or weeks in a frozen state with no breathing and no heart beat, and with up to 65% of total body water as extracellular ice. The biochemical mechanisms involved in natural freeze tolerance include (i) the regulation of extracellular ice formation by proteinaceous ice nucleators in body fluids, (ii) the accumulation of high concentrations of low molecular weight carbohydrates as cryoprotectants to regulate cell volume reduction during freezing and stabilize macromolecular structure, and (iii) a well-developed ischemia tolerance that supports the survival of individual organs while frozen. The present article focuses on recent advances in our understanding of the biochemistry of natural freeze tolerance in lower vertebrates and the application of these studies to the improvement of cryopreservation technology for transplantable mammalian organs. PMID- 2222993 TI - Sensory transduction and the mammalian epidermis. AB - This paper constitutes, in its main intent, an introduction to the mammalian epidermis as a surface for biosensor applications. In particular, the structure and function of the epidermis of the newborn rat are examined as a model for studies of the human state. Data are presented illustrating an anisotropic organization of the dorsal surface of the neonatal rodent with regard to line of tension and thermal gradients. The dependence of the mechanical properties of the epidermis upon calcium is examined by means of an in-vitro assay of epidermal retraction. The potential role of keratin tonofilaments as piezoelectric and pyroelectric elements in the epidermis is introduced and the spatial alignment of these macromolecular arrays is demonstrated to be a function of physiological tensions. These findings are discussed in the context of noninvasive epidermal sensors utilized to understand mechanisms of sensory development and physiological regulation. Optoelectronic (infrared) imaging of the dorsal temperature field and the alteration in this field by treatment with epidermal growth factor are presented as examples of this methodologic approach. It is concluded that a detailed examination of the material and physical properties of mammalian epidermis is a reasonable goal of biosensor development and research. Hypothetically, such studies may reveal important molecular and cellular mechanisms by which sensory data are transmitted or transduced at the organism environmental interface. PMID- 2222996 TI - A possible mechanism for the in vitro activation of L-serine deaminase activity in Escherichia coli K12. AB - L-Serine deaminase is inactive in crude extracts of Escherichia coli K12, but can be activated by incubation with iron and dithiothreitol. This activation requires oxygen, and is inhibited by free radical scavengers and by diethylene triamine pentaacetic acid, which prevents Fe cycling. We suggest that in vitro activation of L-serine deaminase is catalyzed by an oxidant (perhaps hydroxyl radicals). Also, activation may be accompanied by a decrease in molecular weight and involve both a cleavage of the polypeptide chain and a reversible reduction of the molecule. PMID- 2222997 TI - Electroporation-mediated uptake of proteins into mammalian cells. AB - Proteins of up to 230 kilodaltons are taken up by chinese hamster ovary fibroblasts exposed to electroporation under conditions generally similar to those used to mediate DNA transfection. The uptake of catalase, ovalbumin, and histone H1 labelled with fluorescein was visualized by fluorescence microscopy. Under the same conditions, the uptake of colloidal gold particles (20 nm diameter) was visualized by electron microscopy. In optimum conditions, about 25% of the cells remained viable and grew normally and about 25% of these retained labelled proteins during two cycles of further growth. About 6 x 10(4) molecules of catalase were retained per cell. Proteins were taken up when presented to the cells up to 4 h after electroporation, suggesting that mechanisms other than classical electropore formation may operate in these conditions. The proteins were localized in the cytoplasm in a predominantly vesicular pattern and histone H1 entered the nucleus in some cells. PMID- 2222998 TI - Gangliosides and glycophorin inhibit T-lymphocyte activation. AB - Increased levels of gangliosides in the serum have been linked to tumour-induced immunosuppression in vivo. Both bovine brain gangliosides and human erythrocyte glycophorin were potent inhibitors of concanavalin A, periodate, and phorbol ester--ionomycin induced activation of murine T-lymphocytes. Structurally complex gangliosides were more inhibitory, while simpler glycolipids caused less inhibition. Lymphocytes exposed to these molecules for up to 24 h could still proliferate after washing. Substantial inhibition was observed only when gangliosides and glycophorin were present during the first 18 h of activation. Studies using Quin-2 showed that gangliosides did not block the initial rapid rise in cytoplasmic Ca2+ following mitogen stimulation. Interleukin-2 (IL-2) production by ganglioside- and glycophorin-treated lymphocytes was unchanged. After treatment with gangliosides for 24 h, lymphocytes proliferated normally in response to added IL-2. These results suggest that the first round of signal transduction in response to mitogen was unaffected by gangliosides. Addition of gangliosides to activated lymphocytes in the presence of IL-2 resulted in complete inhibition of proliferation. Immunosuppression by gangliosides and glycophorin thus appears to occur at the IL-2-dependent stage of proliferation and may be partially due to IL-2 binding to these molecules. However, high levels of IL-2 failed to reverse inhibition and IL-2-dependent cell lines were much less sensitive to ganglioside inhibition than T-lymphocytes, suggesting that more than one mechanism of inhibition likely exists. PMID- 2222999 TI - The effect of methyl lidocaine on lysophospholipid metabolism in hamster heart. AB - An important feature in the remodelling of fatty acyl chains in cellular phospholipids is the acylation of lysophospholipids. Since lysophospholipids are cytolytic at high concentrations, the acylation reaction may provide an alternate pathway for the removal of cellular lysophospholipids. However, the physiological role of the acylation process in the maintenance of lysophospholipid levels in mammalian tissues has not been clearly defined. In this study, methyl lidocaine was found to inhibit both lysophosphatidylcholine:acyl-CoA and lysophosphatidylethanolamine:acyl-CoA acyltransferase activities in the hamster heart, but the drug had no effect on the other lysophospholipid metabolic enzymes. When the heart was perfused with 0.5 mg methyl lidocaine/mL, acyltransferase activities were attenuated, but there was no change in the activities of phospholipase A or lysophospholipase. The levels of the major lysophospholipids in the heart were not altered by methyl lidocaine perfusion. When the hearts were perfused with labelled lysophospholipid in the presence of methyl lidocaine, there was a reduction in the formation of the phospholipid and an increase in the release of the free fatty acid. However, the labelling of lysophospholipid in the heart was not altered by methyl lidocaine. We postulate that the acylation reaction has no direct contribution to the maintenance of the lysophospholipid levels in the heart. PMID- 2223000 TI - Dual coenzyme activities of high-Km aldehyde dehydrogenase from rat liver mitochondria. AB - Various kinetic approaches were carried out to investigate kinetic attributes for the dual coenzyme activities of mitochondrial aldehyde dehydrogenase from rat liver. The enzyme catalyses NAD(+)- and NADP(+)-dependent oxidations of ethanal by an ordered bi-bi mechanism with NAD(P)+ as the first reactant bound and NAD(P)H as the last product released. The two coenzymes presumably interact with the kinetically identical site. NAD+ forms the dynamic binary complex with the enzyme, while the enzyme-NAD(P)H complex formation is associated with conformation change(s). A stopped-flow burst of NAD(P)H formation, followed by a slower steady-state turnover, suggests that either the deacylation or the release of NAD(P)H is rate limiting. Although NADP+ is reduced by a faster burst rate, NAD+ is slightly favored as the coenzyme by virtue of its marginally faster turnover rate. PMID- 2223001 TI - Esterase activity of high-Km aldehyde dehydrogenase from rat liver mitochondria. AB - Aldehyde dehydrogenase possessing an esterolytic activity has been purified to homogeneity from rat liver mitochondria. Steady-state kinetic studies suggest that the esterolytic reaction follows an ordered uni-bi mechanism. The formation of an acyl enzyme intermediate via nucleophilic catalysis during the esterase reaction is established kinetically using a series of substrates with varying acyl carbon chains and substituted phenyl octanoates with varying electronic effects. The enzyme was reconstituted into phospholipid vesicles. A significant increase in binding capacity is observed when the enzyme is encapsulated into liposomes containing 4% diphosphatidylglycerol. PMID- 2223002 TI - Purification and partial characterization of a mitogenic protein released from preadipocytes of massively obese subjects. AB - A protein released into the culture medium by omental preadipocytes of massively obese persons, which stimulates the replication of rat perirenal preadipocytes, has been purified to a high degree. By gel filtration chromatography, the molecular mass of the mitogenic protein was approximately 66,000 daltons (Da), while on sodium dodecyl sulfate - polyacrylamide gel electrophoresis, two subunits were obtained, relative masses (Mr) of approximately 31,000 and approximately 35,000. The isoelectric point of the approximately 66,000 Da entity was 5.6 +/- 0.2. By specific radioreceptor assay, the purified protein was related to epidermal growth factor and transforming growth factor alpha. It was not related to insulin-like growth factors I and II by radioimmunoassay and radioreceptor assay. We propose that the approximately 66,000 Mr protein, and other mitogenic proteins released by preadipocytes from massively obese persons, act through paracrine-autocrine mechanisms and may play a role in the development of the hyperplasia of enlarged fat cells characteristic of massive corpulence. PMID- 2223003 TI - S-adenosylmethionine and S-adenosylhomocysteine transitions in encysting Physarum flavicomum amoebae. AB - Previous studies from this laboratory suggested that in Physarum flavicomum an S adenosylmethionine (SAM) related metabolic flux is involved in the developmental control of microcyst formation. In the present study, this phenomenon was further analyzed by comparing the metabolic effects of compounds found to favor, stimulate, or inhibit the normal encystment process. The compounds utilized were adenine, cycloleucine, L-ethionine, DL-selenomethionine, cadaverine, cyclohexylammonium sulfate, papaverine, mycophenolic acid, decoyinine, putrescine, spermidine, and spermine. Following incubation with the compounds or combinations of the compounds, the intracellular levels of SAM and SAM metabolites were determined using high performance liquid chromatography. The actual level of the intracellular SAM pool varied considerably (notably after 15 h of incubation), depending on the compound(s) in the incubation solution, but was always highest during inhibition of encystment. SAM was undetectable or barely detectable during stimulation of encystment or under conditions favoring encystment. In cells exposed to L-ethionine, we detected intracellular S adenosylethionine rather than SAM. The intracellular methionine pool in cells encysting normally for 15 h was found to be 1.3 mumol/pg DNA. Both SAM and S adenosylhomocysteine (SAH) were present in growing amoebae at concentrations greater than that of cells undergoing normal encystment. The developmental transition from growing amoebae to dormant cysts in P. flavicomum is metabolically characterized by the adjustment of the intracellular concentration of SAM and SAH to a minimal critical level of 0.31 and 0.70 fmol/pg DNA, respectively. PMID- 2223004 TI - Structural analysis of the specific capsular polysaccharide of Rhodococcus equi serotype 1. AB - The specific capsular polysaccharide produced by Rhodococcus equi serotype 1 was found to be a high molecular weight acidic polymer composed of D-glucose, D mannose, and D-glucuronic acid. Structural analysis of the polysaccharide employed a combination of chemical and nuclear magnetic resonance techniques, from which it was determined that the polysaccharide possessed a linear repeating tetrasaccharide unit containing a single O-acetyl substituent and and acetal linked pyruvic acid moiety: [formula: see text] The 1H and 13C nuclear magnetic resonances of O-deacetylated and pyruvic-free serotype 1 polysaccharides were fully assigned by homo- and hetero-nuclear chemical shift correlation methods. PMID- 2223005 TI - Endogenous heparin-binding lectin activity in human placenta: purification and developmental expression. AB - Human placental extracts contain a herapin-inhibitable lectin activity. The lectin, which closely resembles those from chicken and rat tissues, was purified by heparin-affinity chromatography. It shares many properties with the previously reported lectins, including hapten specificity, molecular weight of monomers, and immunological cross-reactivity. Sections from different stages of placental development, stained by immunohistochemistry procedures using lectin-specific antibody, showed that the lectin was initially present only in cytotrophoblasts of early first trimester villi. Later in the first trimester, both cytotrophoblasts and syncytiotrophoblasts were stained positively for lectin. From second trimester to term, the lectin was seen only in syncytiotrophoblasts. PMID- 2223006 TI - Acidic extracellular environment induces only a subset of heat-shock proteins in primary mouse kidney cell cultures. AB - Exposure of primary mouse kidney cell cultures to acidic medium (pH 5.5) induced the expression of a 70 kilodalton (kDa) protein. This protein was identified as the major inducible heat-shock protein 70 (hsp70) by immunoprecipitation with anti-hsp70 serum and Northern blot analysis with a hsp70 cDNA probe. Maximum induction of the 70-kDa protein at pH 5.5 after 240 min was about 30% of that observed after 60 min of thermal treatment at 43 degrees C. In addition, there was an apparent induction of the glucose-regulated proteins (GRPs) of 76-78 and 98-100 kDa, but not of the other hsps. This subset induction of the heat-shock response by acidic medium suggests that different mechanisms are responsible for the induction of the various families of hsps. PMID- 2223007 TI - Cortisol catabolism by lymphocytes of patients with chronic lymphocytic leukemia. AB - A low rate of catabolism of cortisol by lymphocytes correlates with high sensitivity of the cells to the steroid and causes them to die at a greater rate than control samples. Since lymphocytes of patients with chronic lymphocytic leukemia respond to treatment with glucocorticosteroids and are cortisol sensitive, we attempted to see whether their capability to catabolize cortisol differs from that of normal lymphocytes. No difference was found between the two groups of cells with regard to the pattern of cortisol metabolites. However, the lymphocytes of the chronic lymphocytic leukemia groups showed a total cortisol catabolism per cell that was significantly lower than that of the control group. Patients with low lymphocyte count in peripheral blood showed a relatively higher cortisol metabolism by lymphocytes per cell than those with high counts. PMID- 2223008 TI - Effect of cellular growth state on indices of n - 6 polyunsaturated fatty acid status in human fibroblasts. AB - A 2 x 2 design was employed to examine the effect of cellular growth state and medium serum concentration on potential indices of n - 6 polyunsaturated fatty acid (PUFA) status in human skin fibroblasts. The cells were cultured either as nonmultiplying cell monolayers or as medium-density, log-phase multiplying cells. An interaction of cellular growth state and medium serum concentration influenced the accumulation of 20:3(n - 9), but not 22:3(n - 9), in the cellular phospholipids. The 20:3(n - 9)/20:4(n - 6) ratio was the most sensitive index of n - 6 PUFA status; however, the ratio was significantly affected by cellular growth state. The 22:3(n - 9)/22:4(n - 6) ratio appears to be an index of n - 6 PUFA status in fibroblasts that is not significantly affected by the growth state of cells. PMID- 2223009 TI - Purification and properties of different isoforms of bovine cathepsin B. AB - A rapid purification procedure is described for cathepsin B from bovine liver. After preparation of crude lysosomal extracts, the method only involves DEAE Zeta Prep-Disk chromatography, gel filtration, and fast protein liquid chromatography on Mono-S column. Two active peaks (P1 and P2) of cathepsin B were distinguished. Both presented uncleaved (relative mass (Mr) 30,000) and cleaved (Mr 25,000 + Mr 5000) chains, but different isoforms as revealed by isoelectrofocusing. These two different populations of cathepsin B isoforms nevertheless exhibited similar enzymatic properties. Km and kcat were 114 microM and 52 s-1, and 125 microM and 75 s-1, for hydrolysis of Z-Arg-Arg-NMec by P1 and P2, respectively. Both were rapidly inhibited by low concentrations of E-64 or leupeptin, but were unaffected by cathepsin-L-specific inhibitor Z-Phe-Phe-CHN2. PMID- 2223010 TI - Image analysis of Feulgen-stained c-H-ras-transformed NIH/3T3 cells. AB - Feulgen-DNA content, nuclear phenotypes, and levels of chromatin condensation were evaluated by image analysis in NIH/3T3 cells transformed with the c-H-ras oncogene of T24 cells. Three nuclear phenotypes, differing from those of untransformed control cells and defined in terms of patterns of chromatin condensation, were demonstrated microspectrophotometrically for the tumor cells. Polyploidy could only be observed in nuclei with extensive and deeply stained areas covered with condensed chromatin, i.e., only in a small fraction of the tumor cell nuclear population. The increased chromatin condensation that appeared with cell transformation affected the euchromatin zones. The image analysis provided data that, compared with those obtained in other situations involving cell transformation, could be relevant to the understanding of changes in chromatin supraorganization related to tumorigenesis and to tumor cell diagnosis. PMID- 2223011 TI - Molecular characterization of three mutations in katG affecting the activity of hydroperoxidase I of Escherichia coli. AB - Hydroperoxidase I (HPI) of Escherichia coli is a bifunctional enzyme exhibiting both catalase and peroxidase activities. Mutants lacking appreciable HPI have been generated using nitrosoguanidine and the gene encoding HPI, katG, has been cloned from three of these mutants using either classical probing methods or polymerase chain reaction amplification. The mutant genes were sequenced and the changes from wild-type sequence identified. Two mutants contained G to A changes in the coding strand, resulting in glycine to aspartate changes at residues 119 (katG15) and 314 (katG16) in the deduced amino acid sequence of the protein. A third mutant contained a C to T change resulting in a leucine to phenylalanine change at residue 139 (katG14). The Phe139-, Asp119-, and Asp314-containing mutants exhibited 13, less than 1, and 18%, respectively, of the wild-type catalase specific activity and 43, 4, and 45% of the wild-type peroxidase specific activity. All mutant enzymes bound less protoheme IX than the wild-type enzyme. The sensitivities of the mutant enzymes to the inhibitors hydroxylamine, azide, and cyanide and the activators imidazole and Tris were similar to those of the wild-type enzyme. The mutant enzymes were more sensitive to high temperature and to beta-mercaptoethanol than the wild-type enzyme. The pH profiles of the mutant catalases were unchanged from the wild-type enzyme. PMID- 2223012 TI - A soluble fatty acyl-acyl carrier protein synthetase from the bioluminescent bacterium Vibrio harveyi. AB - An enzyme catalyzing the ligation of long chain fatty acids to bacterial acyl carrier protein (ACP) has been detected and partially characterized in cell extracts of the bioluminescent bacterium Vibrio harveyi. Acyl-ACP synthetase activity (optimal pH 7.5-8.0) required millimolar concentrations of ATP and Mg2+ and was slightly activated by Ca2+, but was inhibited at high ionic strength and by Triton X-100. ACP from either Escherichia coli (apparent Km = 20 microM) or V. harveyi was used as a substrate. Of the [14C]fatty acids tested as substrates (8 18 carbons), a preference for fatty acids less than or equal to 14 carbons in length was observed. Vibrio harveyi acyl-ACP synthetase appears to be a soluble hydrophilic enzyme on the basis of subcellular fractionation and Triton X-114 phase partition assay. The enzyme was not coinduced with luciferase activity or light emission in vivo during the late exponential growth phase in liquid culture. Acyl-ACP synthetase activity was also detected in extracts from the luminescent bacterium Vibrio fischeri, but not Photobacterium phosphoreum. The cytosolic nature and enzymatic properties of V. harveyi acyl-ACP synthetase indicate that it may have a different physiological role than the membrane-bound activity of E. coli, which has been implicated in phosphatidylethanolamine turnover. Acyl-ACP synthetase activity in V. harveyi could be involved in the intracellular activation and elongation of exogenous fatty acids that occurs in this species or in the reactivation of free myristic acid generated by luciferase. PMID- 2223013 TI - 15-Lipoxygenase products affect protein phosphorylation in Friend erythroleukemia cells. AB - Endogenous arachidonic acid metabolism and protein phosphorylation have been examined in Friend erythroleukemia cells in response to the induction of differentiation by dimethyl sulfoxide and hexamethylene bisacetamide. 15 Hydroxyeicosatetraenoic acid levels were elevated in cells differentiated with hexamethylene bisacetamide or dimethyl sulfoxide compared with undifferentiated cells. Protein phosphorylation decreased markedly in differentiated cells compared with undifferentiated cells and the addition of 15 hydroperoxyeicosatetraenoic acid specifically decreased the phosphorylation of a 28-kilodalton protein. These findings indicate that products of 15-lipoxygenase may act as intracellular messengers in Friend erythroleukemia cells by affecting protein phosphorylation. PMID- 2223015 TI - Effect of sulfonates on the esterase activity of carboxypeptidase A. AB - The effects of sulfonates on the carboxypeptidase A catalyzed hydrolysis of the ester substrate benzoylglycyl-L-phenyllactate were determined. The modifiers examined were benzenesulfonate, p-toluenesulfonate, 2-phenylethane-sulfonate, methanesulfonate, ethanesulfonate, propanesulfonate, butanesulfonate, pentanesulfonate, hexanesulfonate, heptanesulfonate, and 2,2-dimethyl-2 silapentane-5-sulfonate. Sulfonate activators of peptide hydrolysis were inhibitors of esterase activity. Of the sulfonates studied, 2,2-dimethyl-2 silapentane-5-sulfonate was the most effective inhibitor. 2 Phenylethanesulfonate, hexanesulfonate, heptanesulfonate, and 2,2-dimethyl-2 silapentane-5-sulfonate exhibited uncompetitive inhibition. The remaining sulfonates either did not inhibit or the inhibition was too weak to properly characterize. PMID- 2223014 TI - Two stress proteins of the endoplasmic reticulum bind denatured collagen. AB - A differentiation-related gelatin-binding 46 kilodalton (kDa) glycoprotein in myoblasts (GP46, colligin) shares several properties with the 78-kDa glucose regulated protein (GRP78), including location in the endoplasmic reticulum and related C-terminal sequences. These similarities extend to stress inducibility, since we find that GP46 is a heat-shock protein; its synthesis is elevated at 42 degrees C, resulting in a two- to three-fold increase in protein level. Further, GRP78 is a gelatin-binding protein; together with GP46 it is retained on gelatin Sepharose beads. GRP78 and GP46 do not interact; each protein can be individually eluted, GP46 at low pH and GRP78 by ATP. These results suggest that the proteins have distinct roles in the synthesis of collagen and point to a simple method for purification. PMID- 2223016 TI - Age-associated changes in the estrogen receptor-active proteases of female rabbit liver. AB - Female rabbit liver cytosol contains a receptor-modifying activity that converts the 250,000 estrogen receptor of liver and uterine cytosol to a 37,000 form. There is an age-dependent increase in this receptor-active protease and in the general protease activity of rabbit liver cytosol, measured with [14C]casein. Sephacryl S-200 chromatography of liver cytosol shows that in the young animal (5 weeks old) the major receptor-modifying activity elutes near the void volume, while in the older animal (13 weeks old) activities having lower molecular weights are present. The general protease activity elution profile is similar to the receptor-active protease profile for the 5-week-old rabbit but not the 13 week-old rabbit. The liver cytosol of the older animal has a high molecular weight protease active toward [14C]casein but not toward the estrogen receptor. The changes in the estrogen receptor forms and the receptor-modifying activity profiles of liver cytosol that occur during development in the rabbit suggest that receptor-modifying activity may initially be associated with the estrogen receptor to form a high molecular weight complex. PMID- 2223018 TI - Heat-stress stimulation of electron flow in a photosystem I submembrane fraction. AB - Oxygen uptake using methyl viologen as the terminal electron acceptor was recorded in digitonin-derived photosystem I submembrane fractions incubated at either 25 or 50 degrees C. A two- to four-fold heat-stress stimulation of electron flow was detected at 50 degrees C when reduced 2,6-dichlorophenol indophenol was used as the primary electron donor. However, no stimulation was seen with N,N,N',N'-tetramethylphenylenediamine as the donor. The stimulation was enhanced by specific cations (Mg2+, Na+, K+), but not by Mn2 or Ca2+. The enhancement obtained with Mg2+ could be eliminated by incubating for a prolonged period. It is proposed that the observed heat-stress stimulation is due to a conformational change at the level of the cytochrome b6-f complex. This change increased the affinity of the protein complex for 2,6-dichlorophenol-indophenol at its oxidation sites. The involvement of a conformational modification is demonstrated by the absence of heat-stress stimulation in submembrane fractions immobilized in an albumin-glutaraldehyde cross-linked matrix. PMID- 2223017 TI - Biochemical aspects of free radicals. AB - Toxic free radicals can be produced by many reactions required for the maintenance of normal metabolism and the production of energy in the cell. The reactivity of both primary and secondary radicals with biomolecules and in whole tissue systems is of interest, not only because of their importance in radiobiology but also because of the role these species play in toxicity and various disorders. Oxidant stress is known to increase the production of free radicals. In the presence of metals, especially iron, these radicals are converted into more damaging species. Trace elements play an important role in many systems that have evolved to deal with free radicals. The dietary status of the cell can affect the preventative antioxidant constituents of the cell. The chain-breaking antioxidant status can clearly be influenced by the dietary content of substances such as vitamins E and C. PMID- 2223019 TI - The mysterious cognitive disorder of Parkinson disease. PMID- 2223020 TI - Subcognitive processing in the frontocaudate "complex loop": the role of the striatum. AB - Anatomical connections between the frontal lobes and basal ganglia have long suggested joint participation in behavioural operations. Early experiments with nonhuman primates and patients are reviewed, followed by current research investigating the specific cognitive routines at risk in Parkinson disease. An hypothesis regarding the functional contribution of the basal ganglia to the frontostriate system is offered. The basal ganglia are considered to set limits on the context within which mental and motor events occur. It is argued that the nature of such processing is subcognitive. PMID- 2223021 TI - Spatial cognition in Parkinson disease. AB - Visuospatial deficits have been found repeatedly in patients with Parkinson disease (PD). However, their precise nature and significance remain controversial. Whereas it is often asserted that primary visuospatial impairments begin early in the disease, others argue that poor performance on visuospatial tasks reflects methodological artifact. This article reviews research on spatial cognition in PD. Five categories of spatial functions are described: visual analysis and synthesis; facial recognition; judgment of direction, orientation, and distance; constructional praxis; and spatial attention. Proposed guidelines for future research include the use of conceptual rather than operational definitions of visual spatial ability, greater attention directed at separating spatial from nonspatial task components, and studies examining basic mechanisms underlying spatial vision. PMID- 2223022 TI - Language and Parkinson disease. AB - Previously published reports of deficits in linguistically oriented tasks were reviewed for both demented and nondemented Parkinson disease (PD) patients in a discussion of the question of whether PD affects language. Additionally, to illustrate the methodological problems inherent in evaluating linguistic competence, the performance on four linguistically oriented tasks of 12 PD patients who scored 8 or better on the Mental Status Questionnaire was compared to that of 32 age- and education-matched control subjects. These tasks, from which a composite variable representing performance was formed, were oral object description, story retelling, the Peabody Picture Vocabulary Test, and the Similarities subtest of the Wechsler Adult Intelligence Scale (WAIS), a test of verbal associative reasoning. After controlling for the effects of disease severity, a significant effect was observed for the presence of PD. However, when the additional effects of performance on the Block Design subtest of the WAIS were controlled, the PD effect was of borderline significance. These results typify those in the literature, that is, whereas nondemented PD patients can be demonstrated to perform significantly more poorly on linguistically oriented tasks, the performance deficit cannot be conclusively demonstrated to result from a language deficit per se. PMID- 2223023 TI - The compassion of distinguishing punishing behavioral treatment from aversive treatment. PMID- 2223024 TI - The ideology and science of punishment in mental retardation. AB - The conflict between those who view aversive therapeutic interventions from an ideological perspective and those who view them from a scientific perspective was examined. Special attention was devoted to the most detailed review of punishment procedures in mental retardation that has been written from an ideological perspective, a monograph published by The Association for Persons With Severe Handicaps (Guess, Helmstetter, Turnbull, & Knowlton, 1986). The monograph was found to suffer from a number of serious conceptual and methodological flaws that militate against accepting its conclusions as bases for research and social policy in mental retardation. The conclusion was drawn that some of those who reject aversive therapeutic interventions do so out of a poor understanding of behavioral science and a primarily ideological frame of reference. PMID- 2223025 TI - Acceptability of behavioral interventions for self-injurious behavior: replication and interinstitutional comparison. AB - Using a case description methodology, Tarnowski, Rasnake, Mulick, and Kelly (1989) examined the effects of behavior problem severity and intervention type on staff ratings of six behavioral interventions used to treat self-injurious behavior (SIB). Results indicated that accelerative interventions were judged more acceptable than reductive treatments, and acceptability of treatments varied as a function of SIB severity. We hypothesized that judgments of treatment acceptability might vary as a function of specific institutional characteristics and conducted a replication of the previous study in a setting where the institutional treatment philosophy was explicitly behavioral. Results indicated that (a) accelerative interventions were preferred to reductive treatments, (b) acceptability ratings were not significantly influenced by SIB severity, and (c) interventions were generally found to be more acceptable by staff working in a behavioral treatment milieu. PMID- 2223026 TI - Teaching self-protection skills to persons with mental retardation. AB - A curriculum for teaching self-protection skills to eight adults with mild mental retardation was evaluated. The curriculum, which was presented in a small-group format across nine 25 to 30 minute sessions, uses instructions, modeling, rehearsal, feedback, and praise to teach skills needed to discriminate and safely respond to abduction and sexual abuse situations. Self-protection skills were assessed in in situ simulations involving solicitations from adults. Results showed that all but one subject learned the criterion skills and maintained them at a 6-month follow-up. Strengths and limitations of the study were discussed and future research directions suggested. PMID- 2223027 TI - Intellectual and adaptive functioning: some tables for interpreting the Vineland in combination with intelligence tests. AB - A set of tables was provided with the differences necessary for statistical significance between the Vineland Adaptive Behavior Scales and the Bayley Scales of Infant Development. McCarthy Scales of Children's Abilities, Stanford-Binet Intelligence Scale (4th ed.), and all current Wechsler intelligence scales. This information may be beneficial in determining whether discrepancies in the Vineland and measures of intelligence can be attributed to chance alone or whether they represent real differences. In light of normative sampling diversity, regression effects, and procedural factors, which result in varying and indeterminate error in the tables, the tables can only augment clinical decision, not replace it. PMID- 2223028 TI - Testing the robustness of the diagnostic overshadowing bias. AB - The robustness of the diagnostic overshadowing bias was examined by (a) testing the relation of overshadowing to level of mental retardation, (b) reexamining the effect of clinical experience in a more sensitive analysis, and (c) extending previous results to rehabilitation counselors. Diagnostic overshadowing was found with individuals with an IQ of 58, but did not generalize to those with IQs 70 or 80. This finding does not support the saliency hypothesis proposed by Reiss and his colleagues. In contrast to earlier studies, experience was related to overshadowing, although results were mixed. Experience measured by number of clients seen was not significant, whereas longevity in the field of mental retardation was associated with increased overshadowing. PMID- 2223029 TI - Musical aptitude and adaptive behavior of people with mental retardation. AB - Musical aptitude was assessed in 16 adults nominated as having special musical interests and/or skills and 16 matched comparison adults. Information pertaining to strengths and weaknesses in adjustment was also obtained. Musical target subjects scored higher on the test of musical aptitude, particularly if they played a musical instrument. Evidence for difficulties in adjustment associated with musical skill or interest was mixed, although, in general, the results suggested no pervasive maladjustment among those with exceptional skill combined with mental retardation. PMID- 2223030 TI - Comment on Hore and Tryon's study of the similar structure hypothesis. PMID- 2223031 TI - EPA releases first interim report to Congress on medical waste management in the U.S. PMID- 2223032 TI - Sources and fates of lead and cadmium in municipal solid waste. AB - Lead and cadmium enter the municipal solid waste stream as components of a variety of consumer products. Average empirical data from several resource recovery plants were analyzed to obtain an estimate of the source and fate of the subject elements. The total amounts of lead and cadmium found in municipal solid waste, determined from empirical data sources, were found to agree closely with those based on materials flow data. It was determined that most of the cadmium enters the waste stream in the combustible fraction and can account for a major share of the cadmium observed in fly ash and in atmospheric particulates. The most likely sources of cadmium are plastics and pigments. The lead emissions appeared to be derived from both combustible and noncombustible discards of batteries, plastics, and pigments. The data suggests that it would be useful to perform mass balance studies to provide primary data for the determination of the most effective methods for managing discards containing lead and cadmium. The purpose of the suggested research is the reduction of lead and cadmium emissions into the environment from resource recovery plants. PMID- 2223033 TI - Indoor nitrogen dioxide exposure and children's pulmonary function. AB - Elevated concentrations of nitrogen dioxide (NO2) are produced in the home by the use of unvented gas appliances. In studies on potential health effects of indoor exposure to NO2, exposure has mostly been estimated from the presence or absence of sources like gas cookers in the home. This leads to misclassification of exposure, as NO2 concentrations in the home depend also on source use, ventilation habits, time budgets, etc. The availability of cheap, passive monitoring devices has made it possible to measure indoor concentrations of NO2 directly in health effects studies, albeit with averaging times of one to several days. So far, it has not been evaluated whether this increases the sensitivity of a study to detect health effects of NO2. In this paper, a comparison is made between NO2 sources and weekly average indoor NO2 measurements, as predictors of pulmonary function in a study among children aged 6-12 years. The relationship between exposure and lung functions was found to be generally non-significant in this study. The results further suggested that in this study, measuring indoor NO2 concentrations with passive monitors offered no advantage over the simple use of source presence as exposure variable. PMID- 2223035 TI - Different types of mucosal adaptation in the ileal reservoir after restorative proctocolectomy. A two-year follow-up study. AB - A histomorphologic study of the pelvic pouch mucosa during the first two years of function was performed in 11 consecutive patients treated for ulcerative colitis. Two types of mucosal adaptation were delineated. Type A response (5 patients) showed stable slight atrophy, normal numbers of goblet cells, and numerous sulphated mucin positive cells. The frequency of mitoses was higher than in the normal ileum. The degree of acute and chronic inflammation was low and decreasing or stable. Dysplasia was never seen. Type B response (5 patients) comprised progressive, finally severe atrophy accompanied by increasing degree of acute inflammation. The number of mitoses was higher than in type A response. In two patients the number of goblet cells was moderately/severely decreased and epithelial atypia or low grade dysplasia occurred repeatedly. The response was regarded as indeterminate in one patient. The determination of the types of mucosal adaptation may help in the planning of the follow-up of these patients. PMID- 2223034 TI - The autopsy and epidemiology--Olmsted County, Minnesota and Malmo, Sweden. AB - The existence of high quality, population-based, medical data facilitates the practice of modern epidemiology with its concomitant benefits for clinical practice and public health policy. Two exceptional examples of such databases are provided by Malmo, Sweden, and Olmsted County, Minnesota. This paper outlines briefly the similarities between these two geographic entities, and focuses, in particular, on the central role of the autopsy in Olmsted County. Changing temporal and spatial patterns of autopsy are reviewed as well as two important related issues: the role of consent and the medico-legal autopsy. The paper concludes with a summary of some of the more noteworthy contributions of autopsy based epidemiological research in Olmsted County, and offers several recommendations for the establishment of a select network of special population based study areas. These epidemiological "laboratories", through the interchange of data and tissue specimens, could make significant contributions to the study of diseases both nationally and internationally. Their interactive efforts and high quality data bases would help to increase the efficiency of the expenditure of scarce societal resources in epidemiology and health care. PMID- 2223036 TI - Quartz-induced production of reactive oxygen metabolites by activated human monocyte-derived macrophages. AB - Quartz but not titanium dioxide (TiO2) induced the production of reactive oxygen metabolites (ROM) by human monocyte-derived macrophages, as measured by lucigenin dependent chemiluminescence. Activation of the macrophages with BCG, bacterial lipopolysaccharide and macrophage-activating factor (MAF) caused a prominent increase of quartz-induced ROM production, MAF having the strongest effect. The activation did not affect the TiO2 responses to the same extent. Assuming that ROM have a role in the pathogenesis of silica-induced disease in man, we suggest that enhancement of quartz-induced production of ROM by activated pulmonary macrophages may at least partly explain the experimental and epidemiological data indicating that activation of the immune system during infection promotes the development of silicosis. PMID- 2223037 TI - Intestinal microbial conversion of cholesterol to coprostanol in man. Influence of antibiotics. AB - The intestinal microbial conversion of cholesterol to coprostanol has been measured in groups of healthy subjects before, during and after they received the antibiotics ampicillin, bacitracin, clindamycin, co-trimoxazole, doxycycline, erythromycin, metronidazole, nalidixic acid, ofloxacin or vancomycin orally for 6 days. Before they received antibiotics, the subjects demonstrated two distinct patterns of cholesterol conversion. One pattern was characterised by extensive conversion of cholesterol, the other by little or no conversion. Intake of bacitracin, clindamycin, erythromycin, metronidazole and vancomycin significantly reduced the conversion to coprostanol. In the groups receiving ampicillin or doxycycline, marked reductions were found in most of the subjects. No alterations were found in the groups receiving co-trimoxazole, nalidixic acid or ofloxacin. In 6 subjects no conversion of cholesterol to coprostanol was found up to 5 weeks after the end of the antibiotic intake. We conclude that orally given antibiotics may cause alterations in the intestinal conversion of cholesterol, reflecting changes in the anaerobic, Gram-positive component of the gut flora. PMID- 2223038 TI - DNA content and nuclear size of megakaryocytes in thrombocythaemia. AB - Total nuclear DNA content and nuclear size of megakaryocytes were studied in biopsies of the iliac bone marrow of individuals with normal or increased platelet counts. The DNA content was determined using Feulgen cytophotometry of bone marrow smears and the nuclear area by morphometric analysis of megakaryocytes of bone marrow sections. The mean DNA content and the mean nuclear area were both significantly larger in megakaryocytes of patients with thrombocytosis as a result of myeloproliferative disease than in patients with secondary thrombocytosis as well as in two control groups of individuals with normal platelets counts, one comprising healthy volunteers, the other with various non-haematological disorders. There was a statistically significant correlation between the DNA content and nuclear area of the megakaryocytes (r = 0.92) in the entire group of bone marrows studied. PMID- 2223039 TI - Effect of astrocyte-derived factors on ischemic brain edema induced by rat MCA occlusion. AB - To clarify whether astrocyte-derived factors may protect cerebral tissue from ischemia, we examined brain edema, demyelination and astrocyte proliferation in brains with focal ischemia and treated with astrocyte-cultured medium. We occluded the left middle cerebral artery of rats and implanted the Osmotic Minipump, which continuously infused the glial-cultured medium or control medium into the left lateral ventricle. Animals were sacrificed at 3 days or 7 days after occlusion. Brains of both groups were compared by several markers, i.e. extravasation of Evans blue, demyelination by Woelcke's staining and glial proliferation by GFAP staining. We found the astrocyte-cultured medium reduced leakage of Evans blue-plasma protein complex from ischemic lesions and reduced the size of demyelinated lesions. However, the degree of astrocyte proliferation was similar in both groups. From these data, we speculate that humoral factors derived from cultured astrocytes lessened the brain edema by modifying the blood brain barrier. These factors might also induce proliferation of the microglia, and may protect the neurons from secondary injury by oxygen-free radicals. PMID- 2223041 TI - Interhemispheric EEG coherence during sleep and wakefulness in left- and right handed subjects. AB - REM sleep is associated with the production of complex imagery sequences. Yet research is divided as to whether different brain regions are more or less coordinated in their functioning at this time. Some research suggests that there may occur a functional disconnection of the left and right cerebral hemispheres during REM sleep which is similar to the disconnection syndrome seen after corpus callosotomy. Other research suggests that an increase in interhemispheric coordination occurs. On the assumption that hemispheric coordination is reflected in the EEG coherence measure, we explored differences in interhemispheric coherence recorded in six left- and six right-handed normal subjects during periods of wakefulness, stage REM, stage 2, and stage 3/4 sleep. Strong evidence was found that mean EEG coherence values are larger during sleep than during waking and that they are approximately equal for the different stages of sleep. Frontal electrode placements demonstrated a slightly different pattern of coherence than central, parietal, or occipital placements. Furthermore, coherence values were larger for left-handed subjects over the occipital region during wakefulness, stage 2, and stage REM sleep, but not during stage 3/4 sleep. Coherence was not different for male and female subjects. These findings oppose the interpretation that a functional disconnection of hemispheres occurs during REM sleep and favor the interpretation that sleep in general is a state of heightened cortical coordination. Moreover, greater interhemispheric coherence over occipital brain regions in left-handed subjects suggests possible differences in the cognitive processes of these subjects during waking and dreaming states. PMID- 2223040 TI - Unawareness of impaired face recognition. AB - We report investigations of the face processing abilities of SP, a right-handed woman who had suffered a subarachnoid haemorrhage from a right middle cerebral artery aneurysm. Although she could correctly assign visual stimuli to the 'face' category without difficulty, SP performed poorly on all other face processing, tasks, including 'closure' (Mooney faces), perception of facial expression, unfamiliar face matching, and identification of familiar faces. Identification of familiar people from nonfacial cues (names) remained relatively well-preserved, but severe impairments were evident on all face recognition tasks. Her errors mostly involved either failures to find a face familiar at all, or misidentification as another familiar person. In face-name learning tasks, there was evidence of 'covert' recognition of faces she failed to recognize overtly. SP's face processing impairment remained stable across a 20-month period of investigation, yet throughout this period she did not think that she had any problems in face recognition, and continued to show lack of insight into this impairment even when directly confronted with its consequences on formal testing. In contrast, SP showed adequate insight into other physical and cognitive impairments produced by her illness, including poor memory, hemiplegia, and hemianopia. We propose that her lack of insight into her face recognition problems involves a deficit-specific anosognosia, resulting from impairment of domain-specific monitoring abilities. PMID- 2223042 TI - Long-term effects of cerebellar pathology on cognitive functions. AB - Twelve patients with circumscribed chronic neocerebellar lesions but without CT evidence of forebrain damage (other than the effects of shunting) were investigated for deficits of cognitive functions. Two different mechanisms were considered as possible causes of cognitive impairment: (1) Damage to the dentato thalamo-cortical projection leading to impairments of cortical functions, and (2) prolonged intracranial pressure resulting in diffuse forebrain damage and subcortical dementia. Patients with lesions in the left neocerebellum showed deficits in cognitive operations in three dimensional space, consistent with the right forebrain dominance for spatial functions. Prolonged intracranial pressure, on the other hand, resulted in a mild overall cognitive impairment. PMID- 2223043 TI - Variations in sex-related cognitive abilities across the menstrual cycle. AB - Sex differences in human cognitive and motor skills may in part be due to organizational or activational effects of sex hormones on the brain. In this study, an extensive battery of cognitive and motor tests was administered to normally cycling women at two phases of the menstrual cycle, in order to detect any hormone-mediated changes in performance. Results confirmed changes across the menstrual cycle on a variety of speeded manual and articulatory measures, and on some nonverbal/spatial tests. The results provide qualified support for the hypothesis that the high levels of gonadal steroids provide qualified support for the hypothesis that the high levels of gonadal steroids present at the luteal phase of the cycle may facilitate skills favoring females, but be detrimental to skills favoring males. The implications of these results for research in the area of human sex differences are discussed. PMID- 2223044 TI - Locus of information in words and the right visual field effect. AB - The right visual field (RVF) advantage found for the identification or classification of words has usually been interpreted as evidence for left hemisphere language functions. It has more recently been explained as the result of the fact that the most informative part of the word, presumably the beginning, is in a region of better visual acuity. It is not clear from existing evidence that the beginnings of words are in fact more informative. The present study assessed the locus of information in words by deleting either the initial or terminal one or two letters. Subjects were required to generate a completion. Regardless of whether subjects were scored as correct for generating the original target word (as would be appropriate in a naming study) or for producing any legitimate word (as would be appropriate for a lexical decision study), the results indicated that most words have more information in the initial letters. Nevertheless, there are exceptions to this rule, and some words have more terminal information. Equal numbers of words with more initial information and with more terminal information were selected for two visual field studies in order to assess the effect of the locus of information on visual laterality. In neither a lexical decision study nor a naming study did locus of information affect the commonly observed right visual field superiority. Thus the distribution of information is not likely to be a major confounding variable in laterality studies employing horizontally presented words. PMID- 2223045 TI - The effects of precocious adrenarche on cognition and hemispheric specialization. AB - Cognitive skills were assessed in 13 females with a history of precocious adrenarche (PA). They were of average intelligence. In terms of lateralized cognitive skills, PA had no effect on verbal fluency. The spatial abilities of females with a history of PA, who had reached gonarche (were fully pubertal), were inferior to those of females tested in the midst of PA and to population controls. The physiologic/hormonal changes associated with normal adrenarche may curtail further specialization of the right hemisphere, resulting in a relative spatial deficit among females in general, who as a group reach adrenarche earlier than males. This spatial performance deficit is exaggerated in females with PA. PMID- 2223046 TI - Hemispheric asymmetries in attentional control: implications for hand preference in sensorimotor tasks. AB - Liepmann (1908) proposed that handedness reflects the greater capacity of one hemisphere to learn the execution of skilled movements. Although asymmetries in motor control are an important basis for hand asymmetries, recent studies have suggested that handedness may be determined by multiple factors. In the present study, we examine how attentional asymmetries may contribute to hand preferences. Right-handed subjects participated in a reaction time task in which they were given preliminary information about where a target stimulus would occur (selective attention) or which hand to use for responding (selective intention). Our findings indicate that these processes influence each other reciprocally and favor a state of optimal attentional and intentional preparation of the right hand. We suggest that these hemispheric asymmetries in attentional control contribute to hand preferences in certain sensorimotor tasks. PMID- 2223047 TI - Selective activation effects of concurrent verbal and spatial memory loads in left-handed and right-handed adults. AB - Thirty-two left-handed subjects, divided into four groups according to sex and familial sinistrality, and 16 right-handed subjects without familial sinistrality (8 male, 8 female) participated in a tachistoscopic unilateral letter identification task with concurrent verbal- and spatial-memory loads. Across groups, a significant right visual field advantage for letter-identification was found. In the majority of both left-handed and right-handed subjects, the concurrent verbal-memory load resulted in a selective activation, with the right visual field performance showing improvement. However, the group of left-handed males with a positive family history of sinistrality gave less evidence of selective left-hemispheric activation as a consequence of the verbal-memory load. The concurrent spatial-memory load did not result in a consistent pattern of selective activation. PMID- 2223048 TI - The lateralization of language comprehension using event-related potentials. AB - Event-Related Potentials were recorded over occipital and parietal scalp from left- and right-handed adults presented with a language and a non-language visual stimulus using a divided field, "oddball" paradigm. The major finding of interest was that the P300 component was larger over the left than the right hemisphere of the right-handers when the language stimulus was presented to the left hemisphere; there were no hemispheric differences for the left-handers, regardless of field of presentation. These results are discussed in the context of developing noninvasive measures to lateralize language function. PMID- 2223049 TI - Neurones in the dorsal motor vagal nucleus of the cat with non-myelinated axons projecting to the heart and lungs. AB - Extracellular recordings were made from ninety-four single motoneurones in the dorsal motor vagal nucleus of chloralose-anaesthetized or decerebrate cats. Fifty five neurones had axons in cardiac vagal branches and thirty-nine had axons in pulmonary vagal branches; the conduction velocities of the axons were in the C fibre range, i.e. the axons were non-myelinated. The neurons exhibited little or no spontaneous activity. Excitatory and inhibitory synaptic inputs were demonstrated by electrical stimulation of the vagus nerve or its branches. Twenty four neurones were tested by carotid sinus distension but only one was excited. Iontophoretic excitation of neurones projecting to cardiac vagal branches had no effect on heart rate. The properties of these neurones and their possible functions are discussed and contrasted with those of cardiac and pulmonary vagal motoneurones in the nucleus ambiguus. PMID- 2223050 TI - 5-Hydroxytryptamine mediates the post-embolic increase in respiratory rate in anaesthetized rabbits. AB - The effect of the neuronal 5-HT3 receptor antagonist MDL 72222 has been investigated on the reflex tachypnoeic response to pulmonary embolism in pentobarbitone-anaesthetized rabbits. Pre-treatment with MDL 72222 (640 micrograms kg-1, 5 min prior to embolization) significantly attenuated the reflex tachypnoeic response associated with the injection of emboli. MDL 72222 had no effect on the bradycardia associated with embolization; however, it significantly reduced the decrease in arterial blood pressure and converted the decrease in tidal volume seen in pulmonary embolism to an increase. Furthermore, MDL 72222 had no effect on the decrease in circulating platelet count associated with embolization. The data suggest that 5-hydroxytryptamine is of primary importance in mediating the post-embolic increase in respiratory rate seen in this model of pulmonary embolism. PMID- 2223052 TI - Lack of interaction between adenosine-induced vasodilatation and carotid baroreflex-induced changes in sympathetic activity in dog hindlimb artery. AB - In anaesthetized dogs, a hindlimb was vascularly isolated and perfused at a constant flow rate of 7.7 +/- 1.9 ml min-1 100 g-1 (mean +/- S.E.M.; n = 5) through the femoral artery. The carotid sinuses were isolated and perfused at high (greater than 145 mmHg) or low (less than 75 mmHg) pressure to enable reflex sympathetic tone on the hindlimb vessels to be controlled. Both vagi were sectioned in the neck and mean aortic blood pressure was held constant by connection of the aorta to a reservoir. The responses to infusion of three doses of adenosine at high and low carotid sinus pressures were not significantly different: infusion of 0.60 +/- 0.16 microM-adenosine reduced femoral arterial perfusion pressure (FAPP) by 11.6 +/- 3.2% (n = 6) at high carotid sinus pressure and by 12.6 +/- 5.1% (n = 4) at low carotid sinus pressure, while 4.71 +/- 0.49 microM-adenosine reduced FAPP by 20.8 +/- 4.8% (n = 6) at high carotid sinus pressure and by 20.7 +/- 4.8% (n = 6) at low carotid sinus pressure; 50.1 +/- 7.3 microM-adenosine reduced FAPP by 36.7 +/- 5.5% (n = 6) at high carotid sinus pressure and by 27.7 +/- 7.8% (n = 5) at low carotid sinus pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223051 TI - The involvement of the midbrain periaqueductal grey in the cardiovascular response to injury in the conscious and anaesthetized rat. AB - Cell bodies within the periaqueductal grey (PAG) of the midbrain of the propofol anaesthetized rat were stimulated using the excitotoxin kainic acid. This resulted in a rise in arterial blood pressure and a tachycardia, together with a reduction in the sensitivity and a rightward resetting of the baroreflex. These changes mimicked the cardiovascular effect of bilateral hindlimb ischaemia in the rat. Further experiments in conscious rats indicated that electrolytic lesions in the PAG prevented the reduction in baroreflex sensitivity induced by limb ischaemia, but did not abolish the rightward resetting of the reflex or the pressor response and tachycardia when compared with sham-lesioned controls. It is postulated that the PAG, a site of importance both in the integration of the defence reaction and the processing of afferent nociceptive information, may form part of a pathway involved in the reduction of the sensitivity of the baroreflex following injury. This pathway is suggested to be separate from a second, as yet undefined, pathway mediating the baroreflex resetting and pressor responses associated with injury. PMID- 2223053 TI - The influence of bicycle exercise, with or without hand immersion in cold water, on forearm sweating in young and middle-aged women. AB - Forearm sweat production rate (SPR) and external auditory meatal temperature (TEAM) were examined in five young and five middle-aged women in response to intermittent exercise, on three separate occasions. The first experiment was a control study, while in the second study the left hand was immersed in cold water at the onset of sweating during each exercise bout, and in the third study this immersion was accompanied by venous occlusion of the upper left arm. TEAM increased by 0.5 degrees C during exercise with no significant differences between the groups on any occasion. The young women displayed a greater peak SPR during exercise in the control than the middle-aged women (52.5 +/- 23.9 vs. 16.7 +/- 6.5 mg cm2 h-1, P less than 0.001). With hand immersion, peak SPR was depressed to 14.0 +/- 4.6 mg cm2 h-1 (P less than 0.001) in the young women and to 13.1 +/- 4.5 mg cm2 h-1 in the middle-aged (P less than 0.05). With hand immersion and venous occlusion the peak SPR in young women increased (43.0 +/- 9.2 mg cm2 h-1). In the older women SPR was 14.9 +/- 6.1 mg cm2 h-1, which was not different from either control or cold-immersed values. Thus, forearm SPR during low-intensity intermittent exercise is greater in young compared with middle-aged women, despite similar changes in TEAM. The response to hand immersion in cold water was more marked in the young subjects. PMID- 2223054 TI - Amylin-amide: a new bone-conserving peptide from the pancreas. AB - Amylin-amide is a new member of the family of peptides encoded by the calcitonin multigene complex. In the present study, we have compared directly, the hypocalcaemic potency and duration of action of human amylin-amide and human calcitonin in an in vivo rat bioassay and an in vitro osteoclast bone resorption assay. Amylin-amide was found to have a potency approximately 40-fold lower than human calcitonin, whilst both peptides followed the same time course. This suggests that amylin-amide is the most potent non-calcitonin hypocalcaemic peptide so far reported. An important physiological implication follows. It would seem that amylin-amide can play a central role in the maintenance of the skeleton by virtue of its inhibitory influence on osteoclastic function. PMID- 2223057 TI - Ammonia absorption from the isolated reticulo-rumen of sheep. AB - In fistulated sheep (50-60 kg live weight) the absorption of ammonia from the reticulo-rumen in vivo was studied applying the technique of the temporarily isolated and washed reticulo-rumen. It was found that, at ammonia concentrations between 3 and 18 mM, ammonia efflux and ammonia net absorption were linearly related to the ammonia concentration in the artificial rumen fluid, whereas influx of ammonia nitrogen from endogenous sources remained almost constant. When the concentration of unionized NH3 was changed at the ratio 1:10:76 by varying the pH from 5.8 to 6.8 and 7.7, ammonia net absorption did not reflect the concentration ratio of unionized NH3, indicating either flux of NH4+ ions or titration of NH4+ to NH3 at the absorptive surface. In the experiments with buffer solutions without ammonium salts and extended over 2 h, ammonia concentrations in the artificial rumen fluid increased due to endogenous nitrogen influx and reached levels far beyond the expected plateau concentration of about 2 mM. Labelling of the N pool in the isolated organ by 15N showed that ammonia efflux had almost ceased in these experiments. It is argued that as yet unidentified changes have taken place in the artificial rumen fluid during the experiment, but there is some reason to believe that volatile fatty acid (VFA) absorption was affecting ammonia absorption. PMID- 2223056 TI - The action of strophanthidin on calcium-activated current and contraction in single guinea-pig ventricular myocytes. AB - Calcium-activated tail current was used as a qualitative indicator of changes in [Ca]i in order to investigate the mechanism of strophanthidin-induced inotropy in single guinea-pig ventricular myocytes. Action potentials were interrupted (by application of a voltage clamp to -40 mV) in order to evoke Ca-activated current. Exposure to 10 microM-strophanthidin for 2 min resulted in an increase in contractions associated with complete action potentials and in an increase in Ca activated current. Strophanthidin appeared not to substantially modify the time course of the envelope of tail currents (recorded by interrupting action potentials at different durations), which is thought to reflect the time course of the systolic [Ca]i transient. Exposure to 1 microM-ryanodine slowed the development of the Ca-activated current envelopes and abolished the above effects of strophanthidin. Exposure to strophanthidin led to reduction in Ca current in a majority of cells (measured by a voltage-clamp step from -40 to 0 mV). These results are consistent with the hypothesis that in single guinea-pig ventricular myocytes strophanthidin causes an increased loading of ryanodine-sensitive intracellular stores of Ca, possibly through reduced extrusion of Ca from the cell by Na-Ca exchange during the action potential plateau. PMID- 2223055 TI - Effects of Ca2+ channel agonist-antagonist enantiomers of dihydropyridine 202791 on insulin release, 45Ca uptake and electrical activity in isolated pancreatic islets. AB - This is the first study using the selective agonist/antagonist stereoisomers of dihydropyridine 202791 to investigate stimulus-secretion coupling in pancreatic islet cells. We studied effects of the (+)(Ca2+ channel agonist) and (-)(Ca2+ channel antagonist) forms of the dihydropyridine, on 45calcium net uptake, insulin secretion, and membrane potential measured in rodent islets. The antagonist partially inhibited glucose-induced insulin secretion and Ca2+ uptake; however, the potassium-induced Ca2+ uptake was completely inhibited. The antagonist did not completely block glucose-evoked spike activity. Addition of the agonist enhanced insulin release and Ca2+ uptake in the presence of 5.6 mM glucose, but did not increase insulin release or Ca2+ uptake in 16.7 mM-glucose. In the presence of tetraethylammonium (TEA), (+)202791 increased and (-)202791 decreased the duration of glucose-induced action potentials. The results again confirm the presence of a dihydropyridine-sensitive Ca2+ channel in pancreatic B cells. In addition these data suggest that in these cells there is activation of a dihydropyridine-insensitive Ca2+ entry in the presence of glucose. PMID- 2223058 TI - Vasoactive intestinal peptide stimulation of adenylate cyclase activity in isolated rabbit renal arterial microvessels. AB - Vasoactive intestinal peptide (VIP) at a concentration of 1 microM stimulates adenylate cyclase (AC) in isolated rabbit renal preglomerular arterial vessels by 3.9 +/- 1.3 fold (n = 6) over basal values. A comparable stimulation of AC was observed with prostaglandin E1. Half-maximal VIP-stimulated activity was observed at 7.2 +/- 3.5 nM (n = 6), which was increased to 17.4 +/- 4.4 nM by 10 microM (4Cl-D-Phe6,Leu17)VIP, a VIP-receptor antagonist. PMID- 2223059 TI - Stimulation of ovine placental transport of calcium and magnesium by mid-molecule fragments of human parathyroid hormone-related protein. AB - Perfusion in situ of the placenta of intact or previously parathyroidectomized fetal lambs has been used to assess the ability of three mid-molecule fragments of the human parathyroid hormone-related protein (PTHrP) molecule to stimulate the placental transport of calcium and magnesium. PTHrP(67-86 amide) was most effective but some activity was also shown by PTHrP(75-86 amide) and by PTHrP (75 84) in decreasing order. This placental action of PTHrP(67-86 amide) was rapid and could be observed using the placenta from an intact fetus, whereas it was necessary to use the placenta from a previously parathyroidectomized fetus to demonstrate stimulation of placental calcium transport by PTHrP(1-84). PTHrP(67 86 amide) may resemble the molecule that activates the placental calcium pump. PMID- 2223060 TI - Abnormal expression of dipeptidylpeptidase IV activity in enterocyte brush-border membranes of children suffering from coeliac disease. AB - Dipeptidylpeptidase IV (DPP IV) activity has been shown cytochemically to decrease significantly in enterocytes of children suffering from coeliac disease. This decrease is due to a halving of the time available for enterocytes to express DPP IV in their brush-border membranes during development. This effect is compared with previous results showing coeliac disease to inhibit disaccharidase activities selectively. PMID- 2223061 TI - IgG subclass deficiency. AB - Although the occurrence of selective deficiencies of serum IgG subclasses has been known for 20 years, the large body of data presently available was collected only recently owing to the use of performing monoclonal antibodies. IgG subclass deficiency is frequent, both as an apparently isolated defect (about one fourth of patients suffering otherwise unexplained repeated infections) and in association with a number of primary and required immunodeficiency states. This paper briefly reviews the methodological problems of serum IgG subclass measurement and data on subclass deficiency in a variety of clinical conditions. PMID- 2223062 TI - Sialophorin (CD43) and the Wiskott-Aldrich syndrome. AB - Wiskott-Aldrich syndrome is an inherited deficiency of T-lymphocyte function and of platelets. The observation in 1981-84 of deficiency and/or defects in Wiskott Aldrich lymphocytes of the surface molecule sialophorin (CD43) spurred intensive study of this molecule. Sialophorin (CD43) is now known to be a prevalent molecule on most circulating blood cells; it is a transmembrane molecule subject to phosphorylation reactions and capable of intracellular signaling. Oligosaccharides constitute 60% of the molecule. The extracellular region resembles acidic mucin molecules with expanded structure and dense negative charge. The sialophorin (CD43) polypeptide is subject to alternative glycosylation pathways that are cell-specific. CD43 functions in vitro as the receptor of an independent pathway of T-lymphocyte and monocyte activation. CD43 is hypothesized to regulate the survival of blood cells in the circulation. This review covers the distribution, chemistry, cDNA cloning, genetic analysis and functional analysis of CD43, and summarizes recent findings of related defects in Wiskott-Aldrich lymphocytes. PMID- 2223063 TI - Pediatric HIV infection: a review. PMID- 2223064 TI - Rapid alkaline transfer of low molecular weight DNA from NuSieve GTG agarose gels. AB - The rapid alkaline transfer of high molecular weight DNA from agarose gels to nylon membranes has greatly decreased the time required for setup of Southern transfers. This technique has been used to resolve genomic DNA greater than 1000 base pairs by conventional electrophoresis on 1% agarose gels followed by alkaline transfer to nylon membrane. Now we report that this rapid alkaline method can be used for the transfer of low molecular weight DNA fragments (10 to 1000 base pairs) from NuSieve GTG agarose gels to nylon membrane. PMID- 2223065 TI - Purification of a thermostable DNA polymerase from Thermus thermophilus HB8, useful in the polymerase chain reaction. AB - A thermostable DNA polymerase, isolated from the thermophilic strain Thermus thermophilus HB 8 was purified by a five-step procedure which provides a high yield and a homogeneous preparation. The molecular weight was estimated to be 67,000 daltons and the extension rate was determined to be 1500 nucleotides per minute. The enzyme works in polymerase chain reaction conditions similar to those used for Taq polymerase from Thermus aquaticus. PMID- 2223066 TI - Expression studies of transfected multigene families by homologous DNA mutagenesis. AB - A valuable approach for multigene family studies where the expression product of at least one gene member of the family is measurable is described. In such cases, the effect on gene expression of nucleotide sequence differences or mutations occurring in other members of the family or at alleles can easily be determined. This is achieved by a strategy called homologous DNA mutagenesis. It consists of the insertion of mutated regions from homologous genes into the context of the gene coding for the assayable product. Here we demonstrate the feasibility of this approach using gene members of the human growth hormone and human placental lactogen (hGH-hPL) multigene family. PMID- 2223067 TI - Thermocycler temperature variation invalidates PCR results. AB - Among the factors which have to be optimized to ensure highest sensitivity and specificity of the polymerase chain reaction (PCR) is the processor which enables the automatic performance of the PCR assay. It has to guarantee temperature homogeneity for all samples of an individual run and run-to-run comparability. The following report illustrates that the present generation of PCR processors does not yet fulfill this requirement to satisfaction. It discusses examples of significant performance variations and their consequences for the outcome of the amplification reaction. PMID- 2223068 TI - A rapid method for the construction of synthetic genes using the polymerase chain reaction. PMID- 2223069 TI - A rapid and inexpensive procedure for desalting synthetic oligonucleotides. PMID- 2223070 TI - Effect of ionic and nonionic detergents on the Taq polymerase. PMID- 2223071 TI - Estimation of quantity of polymerase chain reaction products by ethidium bromide agarose plate assay. PMID- 2223072 TI - A DNA text code. PMID- 2223073 TI - Method for reducing microbial contamination in tissue culture incubators. PMID- 2223074 TI - Electrofused mammalian cells analyzed by free-flow electrophoresis. AB - Somatic cell fusion is a powerful and widely used technique. In recent years, electrofusion has become increasingly popular because it is a gentle process that can be optically controlled and carefully monitored using appropriate fusion chambers and because it permits the efficient fusion of smaller cell numbers. However, damage of the cell membrane and cell lysis occurs during application of the electrical field and is accompanied by changes in surface charge which can be detected by free-flow electrophoresis. In this study, we evaluated free-flow electrophoresis to detect changes in cell viability after application of electric field conditions employed in mammalian cell electrofusion and to separate dead cells and cell debris from intact unfused or fused cells. PMID- 2223075 TI - Selection of invasive and metastatic subpopulations from a heterogeneous human melanoma cell line. AB - The formation and propagation of several subpopulations of human melanoma cells from a heterogeneous parental population was accomplished with the use of the Membrane Invasion Culture System (MICS) in vitro under sterile conditions. Five sequentially selected subpopulations of melanoma cells showed an increasing ability to do the following: a) invade reconstituted basement membranes in vitro; b) form experimental lung metastases in vivo; and c) express steady-state levels of human type IV collagenase, a marker for metastatic potential. In addition, the morphology and expression of 35S-methionine-labeled cell surface proteins changed with sequential selection. The adaptation of the MICS assay for studying tumor cell subpopulations allows the morphological, biochemical and molecular characterization of events associated with tumor progression in an in vitro model. PMID- 2223076 TI - Sphere-linked immunodiagnostic assay (SLIDA): an electron microscopic method for detecting specific antibodies. AB - We have developed a sensitive method, sphere-linked immunodiagnostic assay, using specific antigens covalently bonded to microspheres for the detection of antibodies in serum. In this method, specific antigens, such as the capsid proteins of tobacco mosaic virus and tobacco etch virus, were independently, covalently bonded to plastic micropheres of 0.5 microns or 0.9 microns in diameter. The antigen-linked spheres were then exposed to normal serum or serum containing specific antibody, followed by treatment with gold-labeled secondary antibodies. The binding of the gold-labeled secondary antibodies to the specific primary antibodies on the spheres acted as an indication of the presence of the specific primary antibodies. The spheres were then examined and photographed by transmission electron microscopy. The number of gold particles bound to the spheres was counted manually using the photographs. The gold labeling was found to be specific and sensitive, enabling detection of antibodies present in highly diluted antisera. The efficiency and sensitivity of the technique for detection of antibodies were compared with those of the enzyme-linked immunosorbent assay and found to be highly sensitive. The technique was also used for testing for the presence of antibodies to herpes simplex virus as well as antibodies to Staphylococcus enterotoxin using microspheres coated with the respective antigens. We believe that this technique could be applied clinically when needed for detection of antibodies to other viruses, such as the Human Immunodeficiency Virus. PMID- 2223077 TI - An advanced affinity membrane for covalent binding of amino ligands. AB - We report here an advanced, chemically active and yet hydrolytically stable microporous membrane which allows permanent covalent binding of amino ligands such as proteins. Rapid, single-step immobilizations produce a high density of immobilized ligands. Surface chemistry of the membrane is specifically designed to have extremely low nonspecific binding. Binding characteristics of the UltraBind membrane, various immobilization techniques and optimum immobilization conditions for diagnostic immunoassays are described. PMID- 2223078 TI - Production of plasmid DNA in a simple, inexpensive and reusable fermentor. AB - Performance data for the production of plasmid DNA in bacterial cultures have been obtained using a new concept of simplified fermentor, the Lofstrand Bactolift. The unique design of this fermentor incorporates a standard 500-ml or 1-liter centrifuge bottle as the bacterial growth vessel, thus eliminating the necessity to transfer the cultures for subsequent processing. Bacterial and plasmid yields have been shown to be equal to or greater than those obtained using conventional shake flasks. Twelve 1-liter Bactolift fermentors can be operated in a standard laboratory water bath that occupies less than two square feet of bench space, as compared to a limit of six 2.8-liter Fernbach flasks containing one liter of culture held in an incubator shaker cabinet that occupies nine square feet of laboratory floor space. PMID- 2223079 TI - Mouse zygotes express endogenous lectins. AB - Cell interactions during mouse development have been shown to involve carbohydrate-containing macromolecules (glycoconjugates). We have therefore used a series of fluorescein-labelled synthetic glycoproteins to determine if mouse oocytes and zygotes also express sugar binding molecules (endogenous lectins) which might participate in such interactions. Unfertilized secondary oocytes did not express endogenous lectins at 4 degrees C but a low level of expression of fucose, mannose, and galactose-binding activity could be detected at 37 degrees C. In contrast, the zygote clearly expressed three classes of endogenous lectins, with preferential binding for i) fucose or mannose, ii) glucose or galactose, and iii) lactose. The expression of these lectins was much reduced at 4 degrees C and maximal binding at 37 degrees C was achieved only after 2 h incubation. We therefore conclude that a low level of endogenous lectin expression in the mouse oocyte is greatly enhanced after fertilisation and that, at both stages, expression, or the detection of expression, is markedly temperature dependent. PMID- 2223080 TI - Chymotrypsin-like enzymes are involved in sperm penetration through the vitelline coat of Ciona intestinalis egg. AB - In Ciona intestinalis, sperm penetration through the egg vitelline coat is an essential event of fertilization. We investigated whether trypsin- and chymotrypsin-like enzymes are involved in this event. Inhibitors and peptide substrates for chymotrypsin-like enzymes blocked the overall process of fertilization in a concentration-dependent manner. The inhibitory activity was specifically exerted on the step of sperm penetration. Chymotrypsin-like protease activity was identified in spermatozoa with the fluorogenic synthetic substrate Suc-Ala-Ala-Phe-AMC, which was the most effective substrate in blocking sperm penetration. These data indicate that a chymotrypsin-like protease activity is a sperm lysin of Ciona intestinalis. PMID- 2223081 TI - Maturation-associated changes in the rat zona pellucida. AB - Rat follicular oocytes, arrested at prophase I, cannot be fertilized in vitro. This capacity is acquired following resumption of meiosis and a series of changes involving both the oocyte and the cumulus cells surrounding it. Oocytes exposed to sperm at different hours before ovulation show a gradual increase in the permeability of their zona pellucida (ZP). Our study examined whether the ZP, in response to the physiological stimulus for maturation and concomitant with the other oocyte--cumulus components, undergoes maturational changes. Two ZP characteristics were assessed, sensitivity to proteolysis and sperm binding. ZP surrounding oocytes and eggs were collected from five sources: 1) germinal vesicle (GV)-intact oocytes, 2) preovulatory eggs, 3) ovulated eggs isolated from oviducts of immature females, 4) fertilized eggs, 5) ovulated eggs isolated from oviducts of mature females. All ZP surrounding oocytes/eggs from groups 1-5 were dissolved by trypsin. When solubility by pronase and alpha-chymotrypsin was examined, a large variation between groups was found. All ZP from group 2 were dissolved by 0.001% pronase, compared to 0% solubility in group 4. Only 10% of the ZP surrounding GV-intact oocytes (group 1) were dissolved by this enzyme, compared to 82% in group 3. Solubility in 0.01% alpha-chymotrypsin showed a similar pattern. Capacitated sperm were incubated with eggs from groups 1 and 3. The number of sperm binding to ZP in group 3 was repeatedly higher than that in group 1. In both tests it was found that the ZP surrounding the mature eggs differ in their characteristics from ZP of GV-intact oocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223082 TI - Immunocytochemical studies of hamster oocyte activation. AB - By indirect immunofluorescence, using rabbit anti-heparin-binding placental protein (HBPP) antiserum, we studied HBPP expression by physiologically and non physiologically (microsurgically) activated hamster gametes. Whereas mature gametes (sperm, metaphase II oocytes) were negative, in vivo conceived preimplantation embryos, from pronuclear to two- and four-cell stages, were HBPP positive. No HBPP was demonstrated in the zona pellucida, but HBPP-dependent immunofluorescence was localized in the perivitelline space. Oocytes incubated with hyaluronidase demonstrated variable responses from negative to positive. (Diluent or sperm) microinjected oocytes were all activated and HBPP positive within 4 h after stimulation. Thus neither activation by microinjection nor HBPP expression required paternal gametes. These kinetics suggest that HBPP may be a cortical granule secretogogue which can be applied to monitor oocyte responses during in vitro manipulations. PMID- 2223083 TI - Spermiogenesis in Xenopus laevis: from late spermatids to spermatozoa. AB - Spermatogenesis is a complex morphogenetic process in which microfilaments and microtubules have been shown to play an important role. The last steps of Xenopus spermatogenesis, i.e., the corkscrew shaping of the sperm head, have been followed to study actin and microtubule distribution by conventional and immunoelectron microscopy. During sperm head morphogenesis, actin is absent in the elongating spermatids, but it is present in the Sertoli cells where results localized at the periphery of their cytoplasm that surrounds the developing germ cells. Sertoli cell actin and microtubules may assist the elongation and the shaping of the spermatids and function in maintaining the Sertoli-spermatid association. PMID- 2223084 TI - Injection of isolated centriolar complex to induce mitosis in starfish eggs. AB - When centriolar complex isolated from starfish spermatozoa was injected into starfish immature oocytes (fully grown, germinal vesicle stage) followed by treating the latter with 1-methyladenine, mitotic events such as condensation and division of chromosomes of the female pronucleus and cytokinesis following completion of meiosis were observed. No cortical reaction detected in the oocytes. Essentially the same was noted for mature oocytes (pronuclear stage) into which the centriolar complex had been injected. The oocytes that had received sperm tail fraction or buffer alone did not initiate cleavage. It would thus appear that sperm centriolar complex is significantly essential to the initiation of cleavage. PMID- 2223085 TI - In vitro fertilization of horse follicular oocytes matured in vitro. AB - In vitro fertilizing ability of stallion spermatozoa was assessed using horse follicular oocytes matured in vitro. After collection, stallion spermatozoa were either: 1) washed and incubated in TALP medium with 3 mg/ml bovine serum albumin (BSA) and 10 micrograms/ml heparin for 4h, 2) washed and incubated in TALP with 3 mg/ml BSA for 3 h and cultured for a further 1 h with 1 mM caffeine and 5 mM dbcAMP, 3) washed and incubated in TALP medium with 3 mg/ml BSA at pH 7.9-8.2 for 2-4 h, or 4) diluted and incubated in TALP medium with 10 mg/ml BSA and 7.14 microM calcium ionophore A 23187 for 5-10 min followed by washing. After a given pretreatment, suspensions were diluted into B2 medium to a concentration of 5 x 10(6) sperm/ml and co-incubated with oocytes for 12 h or 24-48 h. In the ionophore-treated group, 18 of 54 oocytes (33%) were fertilized by 12 h, and 11 of 45 (24%) cleaved by 24-48 h. Evidence of fertilization was not found in the oocytes incubated with spermatozoa from other treatment procedures. PMID- 2223086 TI - Changes in calmodulin compartmentalization throughout capacitation and acrosome reaction in guinea pig spermatozoa. AB - Calmodulin has been postulated as a mediator in the calcium-dependent processes that culminate in the acrosome reaction. Changes in calmodulin compartmentalization as a consequence of the increased permeability to extracellular calcium during capacitation and acrosome reaction have been suggested. In the present study the temporal localization of calmodulin in guinea pig spermatozoa was studied during in vitro capacitation and acrosome reaction by indirect immunofluorescence. Capacitation was achieved by incubation in Tyrode medium supplemented with pyruvate, lactate, and glucose in the presence and in the absence of calcium. Acrosome reaction was elicited in three different conditions: 1) by transfer to minimal culture medium containing pyruvate and lactate (MCM-PL) after in vitro capacitation 2) by 0.003% Triton-X 100 treatment, and 3) by A 23187 addition to sperm samples incubated in MCM-PL. During capacitation, calmodulin was observed both in the acrosome and in the flagellum; this localization seemed to be independent of the presence of extracellular calcium and of exogenous substrates. Throughout the acrosome reaction, different stages of calmodulin compartmentalization were observed. It became clustered around the equatorial region just before or a little after the acrosome reaction had occurred. Later, it was observed around the postacrosomal region in the acrosome-reacted sperm. The changes in calmodulin distribution were found to be dependent on the stage in the acrosome reaction. PMID- 2223087 TI - Effect of oviduct cells on the incidence of polyspermy in pig eggs fertilized in vitro. AB - The consequences of interactions between porcine sperm, eggs, and oviduct cells before and during fertilization in vitro (IVF) has been examined with particular reference to the block to polyspermy. The pattern of polypeptides secreted by porcine oviduct epithelial cells has been determined and its effects on sperm both during pre-fertilization co-culture and during fertilization have been examined. In standard IVF procedures with no oviduct cell involvement, high rates of penetration (91%) were accompanied by equally high rates of multiple sperm penetration (91% of penetrated eggs). Fertilization on oviduct cell monolayers or a combination of 1 h co-culture of sperm and oviduct cells before the addition of in vitro matured oocytes did not reduce polyspermy. However, a sperm-oviduct cell co-culture period of 2.5 h followed by IVF on oviduct cells selectively reduced the rate of polyspermy by 40% and 50% in two separate series of trials (United Kingdom and Japan, respectively): Overall fertilization rates after this treatment were high (95% or 84%, respectively). A 3.5 h period of pre fertilization co-culture further reduced polyspermy to only 14% of penetrated eggs, but this treatment was accompanied by a sharp drop in the fertilization rate from an overall mean of 88% for all other groups to 19% after 3.5 h co culture. PMID- 2223088 TI - Stage-specific expression of phosphoprotein p19 during spermatogenesis in the rat. AB - The expression of phosphoprotein p19, a 19-kDa cytosolic substrate for cyclic adenosine monophosphate (cAMP)-dependent protein kinase, occurs abundantly in brain and testis and is developmentally regulated. In the present study we have identified the cell types of adult rat testis that contain p19. Using cryostat sections, which were first incubated with rabbit anti-p19 for immunohistochemistry followed by counterstaining with periodic acid-Schiff (PAS) hematoxylin to reveal nuclear morphology, we demonstrate that immunoreactive p19 is detectable only in germ cells and is restricted to a limited stage of spermatogenesis. Expression first appears after the differentiating gametes have entered the prophase of meiosis, is abundant in spermatocytes until meiosis is completed, and declines to undetectable levels in maturing spermatids. We have ruled out immunocross-reactivity with SCG10, a 22-kDa protein that is closely related in structure to p19, by demonstrating, using Northern blot analysis, that RNA transcripts encoding SCG10 are not detectable in adult rat testis, whereas p19 is abundantly expressed. The transient expression of p19 during spermatogenesis suggests that the protein plays a role during male gamete differentiation. PMID- 2223089 TI - Glycosaminoglycans in porcine follicular fluid promoting viability of oocytes in culture. AB - The viability of oocytes cultured in vitro was determined by the trypan blue exclusion test. Isolated porcine oocytes with or without cumulus cells cultured in modified Krebs-Ringer medium undergo cell death after 48 h. The addition of glycosaminoglycans (GAGs) prepared from porcine follicular fluid (pFF) to the medium delayed or prevented the onset of cell death in vitro. GAGs at concentrations of 0.25 mg/ml or greater prevented cell death in a dose-dependent manner. To identify the active factor, GAGs were purified from pFF by ethanol precipitation, chromatography on Dowex 1-x2, and high performance liquid chromatography (HPLC) on TSK gel DEAE-2 SW column. The fraction with a retention time nearly coincident with that of hyaluronic acid possessed high oocyte viability promoting activity. The present results suggest that the viability of oocytes in vitro is influenced by the presence of specific GAGs separated from follicular fluid. PMID- 2223090 TI - Two proliferative stages of the oligodendrocyte lineage (A2B5+O4- and O4+GalC-) under different mitogenic control. AB - Cell proliferation during successive stages of oligodendrocyte development was delineated in the rat brain and optic nerve. Surface antigens, A2B5, O4, and galactocerebroside (GalC) identified three cell populations emerging in sequence; the incorporation of bromodeoxyuridine into newly synthesized DNA identified the proliferative cells. In vivo, progenitor cells with phenotypes A2B5+O4- and A2B5+O4+GalC- were both proliferative, whereas differentiated GalC+ oligodendrocytes were not. Under basal conditions of culture, the proliferation of both progenitor cell types of the optic nerve was nearly abolished. Activity was restored for A2B5+O4- precursor cells with medium conditioned by either type 1 astrocytes, meningeal cells, or cerebellar interneurons. In contrast, intermediate O4+GalC- cells (proligodendrocytes) were refractory to the astroglial and meningeal signals, but remained as responsive as their precursor cells to the neuronal stimulus. These data further characterize the O4+GalC- proligodendrocyte as a distinct developmental stage, one that specifies a changing response of the cell to environmental mitogens. PMID- 2223091 TI - Antibodies that recognize astrotactin block granule neuron binding to astroglia. AB - To provide a rapid, specific assay for receptor systems involved in the binding of cerebellar granule neurons to astroglia, granule cells, purified from early postnatal mice, or from E15-E16 chicks, were radiolabeled with [35S]methionine and plasma membranes were prepared. The kinetics of binding of radiolabeled material to primary mouse or chick glia or to the mouse G26-24 astrocytoma cell line was measured in the presence or absence of antibodies against astrotactin, neural cell adhesion molecules, cadherins, or integrins. Addition of Fab fragments of astrotactin antibodies reduced the amount of granule cell membrane binding to astroglia by 70%. In contrast, Fab fragments of antibodies against the neural adhesion molecules N-CAM, L1, and N-cadherin and against integrin did not reduce the level of granule cell membrane binding to astroglia. Combinations of antibodies against N-CAM, L1, N-cadherin, and integrin also did not impair neuron binding to glia. PMID- 2223092 TI - A neuronal cell line (PC12) expresses two beta 1-class integrins-alpha 1 beta 1 and alpha 3 beta 1-that recognize different neurite outgrowth-promoting domains in laminin. AB - Integrins mediate neuronal process outgrowth on components of the ECM. Integrin alpha subunit-specific antibodies have been used to examine the roles of individual beta 1 integrins in attachment and neurite outgrowth by the neuronal cell line, PC12, in response to laminin and collagen. alpha 1 beta 1 and alpha 3 beta 1 were identified as the major beta 1 integrins expressed by PC12 cells. In functional assays, both alpha 1 beta 1 and alpha 3 beta 1 mediated PC12 cell interactions with laminin, whereas alpha 1 beta 1 alone mediated responses to collagen types I and IV. alpha 1 beta 1 and alpha 3 beta 1 were shown to recognize two different neurite-promoting sites in laminin: alpha 1 beta 1 interacted with the cross-region of laminin present in proteolytic fragments E1-4 and E1; alpha 3 beta 1 recognized a site in the long arm contained in laminin fragment E8. Thus, PC12 cells express two beta 1 integrins, which together function in attachment and neurite outgrowth on laminin and collagen. These integrins are candidates for mediating neurite outgrowth of sympathetic and other neurons in response to these ECM components. PMID- 2223093 TI - Phosphorylation affects voltage gating of the delayed rectifier K+ channel by electrostatic interactions. AB - The delayed rectifier K+ channel of the squid axon undergoes a series of modifications in its kinetic and conductive parameters when it is phosphorylated as the result of shifts in its voltage-dependent parameters. These effects can be interpreted as due to electrostatic interaction between the voltage sensor of the channel and the transferred phosphate from ATP. Using different concentrations of intracellular Mg2+, we determined the density of surface charges seen by the K+ channel voltage sensor before and after phosphorylation. Values for the surface charge density in the cytoplasmic side of the membrane were between 1/350 and 1/250 e-/A2 in the absence of ATP and between 1/160 and 1/155 e-/A2 under phosphorylating conditions. Incorporation of a surface potential into a kinetic model for the delayed rectifier channel can predict quantitatively phosphorylation-like changes in K+ currents. These results provide evidence for the importance of electrostatic interactions as one of the mechanisms by which phosphorylation modulates the behavior of voltage-dependent channels. PMID- 2223094 TI - A potassium channel gene is expressed at neural induction. AB - Voltage-dependent potassium currents exhibit specific time tables of functional differentiation and regulate the development of action potentials in amphibian spinal neurons. A Xenopus nucleotide sequence (XSha2) encoding a potassium current has been isolated by homology screening with the Drosophila Shaker gene. Functional expression in oocytes identifies it as a delayed rectifier. Southern analysis suggests that XSha2 is a member of a family of highly related genes. XSha2 is expressed in the nervous system but is not detectable in skeletal muscle. Transcripts are apparent at the neural fold stage, and subsequent levels parallel those of the neural marker N-CAM. Thus molecular events required for the establishment of electrical excitability in the vertebrate embryo occur early during neurogenesis. PMID- 2223095 TI - Cytosolic Ca2+, exocytosis, and endocytosis in single melanotrophs of the rat pituitary. AB - We have monitored cytosolic [Ca2+] with fura-2 and exocytosis by measuring the membrane capacitance, and we have studied the influence of cytosolic [Ca2+] on secretion in single endocrine cells. As in neurons, cytosolic Ca2+ is sufficient to trigger exocytosis. The rate of secretion grows with the fourth or fifth power of cytosolic [Ca2+], and paired stimuli reveal facilitation. Ca2+ influx through voltage-sensitive Ca2+ channels can stimulate secretion 1000-fold over the basal levels measured biochemically. Unlike neurons, however, melanotrophs continue to secrete for seconds afer a depolarizing pulse, while they extrude or sequester the Ca2+ that has entered through Ca2+ channels. Following episodes of secretion, pituitary cells can retrieve membrane with half-times around 30 s at 32 degrees C, even in the absence of cytosolic K+. PMID- 2223096 TI - The LEC-CAMs: an emerging family of cell-cell adhesion receptors based upon carbohydrate recognition. AB - Cell surface carbohydrates, because of their demonstrated and potential structural diversity, have long been considered as excellent candidates for determinants of cell-cell recognition. Recently, a gene family has been identified, which encodes a series of three adhesion proteins (pnHR, ELAM-1, and GMP-140), designated as the LEC-CAMs. Each receptor participates in highly specific cell-cell recognition events within the blood vascular compartment. The LEC-CAMs share a high degree of sequence homology and the same organization of protein motifs, which includes a calcium-type lectin domain at the extracellular amino-terminus of each. In the case of the pnHR (peripheral lymph node homing receptor), the lectin domain has been shown to be central to the adhesive function of the receptor, i.e., lymphocyte attachment to high endothelial venules (HEV) of lymph nodes. The cognate ligand for the pnHR on HEV is a sialylated glycoprotein. Sialic acid is required for the adhesive function of this ligand, and preliminary evidence suggests that this requirement may also apply to the ligand for GMP-140. It is not clear as yet whether sialic acid contributes directly to recognition determinants of these ligands or has a modulating effect on their function. Given the extreme diversity of sialyloligosaccharides, the former possibility is very attractive. The LEC-CAM family joins the three families of already identified cell-cell adhesion molecules (integrins, cadherins, and superimmunoglobulins). It remains to be seen whether additional examples of highly specific cell recognition events rely on as yet unidentified LEC-CAMs or related lectin-like receptors. PMID- 2223097 TI - The importance of mouse, rat, and dog mast cell lines. PMID- 2223098 TI - A chemical mismatch cleavage method useful for the detection of point mutations in the p53 gene in lung cancer. AB - Point mutations in genes can be etiologic of pulmonary diseases, as in the case of the inherited disorders alpha-1-antitrypsin deficiency and cystic fibrosis or in the context of dominant and recessive oncogenes in lung cancer. Various methodologies have been developed to screen for single-base mutations. These techniques include direct DNA sequencing, RNase protection, denaturing gradient gel electrophoresis, and chemical mismatch cleavage. The latter method offers the advantages of rapid and efficient analysis of genomic or cDNA and is thus ideally suited to screening applications. Furthermore, all possible single-base changes can theoretically be detected. In the present work, chemical mismatch cleavage was utilized to detect mutations in the p53 gene in small cell and non-small cell lung cancer. This technique was modified by using a two-step, hemi-nested PCR procedure for preparation of target genomic DNAs permitting an expanded target size for analysis. Evaluation by chemical mismatch cleavage of eight p53 cDNAs derived from lung tumors shown to have different mutations by DNA sequencing correctly detected the presence of a point mutation in all instances. Analysis of six additional tumor genomic DNAs with defined mutations in the corresponding p53 cDNAs accurately confirmed the mutation at the level of the genome. The technique also identified codon 72 and intron 6 polymorphisms. Using the intron 6 polymorphism, loss of heterozygosity at the p53 locus in tumor DNA was readily detected by chemical mismatch cleavage. Finally, utilizing this technique for scanning analysis of the p53 gene of uncharacterized lung tumor DNAs, additional mutations were identified in a prospective manner which were confirmed by sequence analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223099 TI - Cyclic biaxial strain of pulmonary artery endothelial cells causes an increase in cell layer-associated fibronectin. AB - Bovine pulmonary artery endothelial (PAE) cells were cultured on an artificial compliant substrate (Mitrathane) and were strained biaxially at a frequency of 1/s for 2, 4, 6, 7, or 24 h. Total protein synthesis, determined by estimating the incorporation of radiolabeled precursors into nondialyzable protein, was increased in cultures that had been biaxially strained for 6, 7, or 24 h, with differences more apparent in the cell layer fraction than in the medium fraction. Medium and cell layer-associated fibronectin were quantitated by enzyme-linked immunosorbent assay and by densitometric analysis of the autoradiograms of electrophoresed protein. Fibronectin levels in the medium of biaxially strained cells were initially depressed in comparison to nonstrained controls but, with time, began to approach control values. Cell layer-associated fibronectin of biaxially strained cultures was significantly elevated at 24 h, whereas DNA synthesis was not altered. Immunohistochemical localization of fibronectin and factor VIII-von Willebrand antigen revealed a more intense staining pattern in strained cultures. Distribution of stress fibers containing fibrous actin was visualized by staining with rhodamine-phalloidin and was altered in strained cultures. These observations indicate that cells respond to cyclic biaxial strain by selectively enhancing structural components associated with cell adhesion. PMID- 2223101 TI - Expression of mucin synthesis and secretion in human tracheobronchial epithelial cells grown in culture. AB - The effects of culture conditions on growth and differentiation of human tracheobronchial epithelial (HTBE) cells have been defined. Epithelial cells were dissociated from tissues by protease treatment and were plated on tissue culture dishes in F12 medium supplemented with insulin, transferrin, epidermal growth factor, hydrocortisone, cholera toxin, bovine hypothalamus extract, and retinol. HTBE cells did not express any mucociliary function (ciliogenesis or mucin secretion) on tissue culture plastic, but they could be passaged 3 to 5 times with a total of 10 to 25 population doublings. Cells from early passages re express both these functions when transplanted to tracheal grafts. When tissue culture plates were coated with collagen film or collagen gel substrata, cell attachment and proliferation were stimulated. However, the expression of mucous cell function in culture occurred only when cells were plated on collagen gel substrata and vitamin A (retinol) was present in the medium. Mucous cell differentiation under optimal conditions was defined by ultrastructural studies, by immunologic studies with mucin-specific monoclonal antibodies, and by carbohydrate and amino acid compositional analyses of mucin-like glycoproteins purified from culture medium. These results demonstrate for the first time that HTBE cells can express mucin synthesis and secretion under appropriate culture conditions. PMID- 2223100 TI - Hypoxic contraction of cultured pulmonary vascular smooth muscle cells. AB - The cellular events involved in generating the hypoxic pulmonary vasoconstriction response are not clearly understood, in part because of the multitude of factors that alter pulmonary vascular tone. The goal of the present studies was to determine if a cell culture preparation containing vascular smooth muscle (VSM) cells could be made to contract when exposed to a hypoxic atmosphere. Cultures containing only fetal bovine pulmonary artery VSM cells were assessed for contractile responses to hypoxic stimuli by two methods. In the first, tension forces generated by cells grown on a flexible growth surface (polymerized polydimethyl siloxane) were manifested as wrinkles and distortions of the surface under the cells. Wrinkling of the surface was noted to progressively increase with time as the culture medium bathing the cells was made hypoxic (PO2 approximately 25 mmHg). The changes were sometimes reversible upon return to normoxic conditions and appeared to be enhanced in cells already exhibiting evidence of some baseline tone. Repeated passage in culture did not diminish the hypoxic response. Evidence for contractile responses to hypoxia was also obtained from measurements of myosin light chain (MLC) phosphorylation. Conversion of MLC to the phosphorylated species is an early step in the activation of smooth muscle contraction. Lowering the PO2 in the culture medium to 59 mmHg caused a 45% increase in the proportion of MLC in the phosphorylated form as determined by two dimensional gel electrophoresis. Similarly, cultures preincubated for 4 h with 32P and then exposed to normoxia or hypoxia for a 5-min experimental period showed more than twice as much of the label in MLCs of the hypoxic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223103 TI - Surfactant apoprotein A (SP-A) is synthesized in airway cells. AB - The pulmonary surfactant apoproteins A, B, and C (SP-A, SP-B, and SP-C, respectively) function in concert with surfactant phospholipids to reduce surface pressure in the alveolus. Surfactant apoproteins also regulate surfactant synthesis, secretion, adsorption, and recycling. SP-A and B have been localized by immunocytochemistry to alveolar epithelial (type II) cells, alveolar macrophages, and nonciliated bronchiolar epithelial (Clara) cells. In contrast, in situ hybridization to SP-A and B mRNA in human lung has shown SP-A and B transcripts in type II cells, but only SP-B message in Clara cells, implying that synthesis of SP-A occurs exclusively in type II cells. In this report, in situ hybridization to SP-A mRNA was performed on adult and developing rabbit lung and on human lung. SP-A transcripts were found in type II cells and bronchiolar epithelium of both species. The distribution of SP-A message-containing cells in the bronchiolar epithelium of rabbits and humans was similar to the distribution of Clara cells in these two species. These data indicate that SP-A is not only synthesized in type II cells but also in Clara cells. PMID- 2223102 TI - Fatty acid supplementation protects pulmonary artery endothelial cells from oxidant injury. AB - Although supplemental fatty acids have been shown to alter the susceptibility of experimental animals to oxidant gases, the relationship between the degree of tissue fatty acyl unsaturation and resistance to oxidant exposure remains undefined. Because vascular endothelial cells have been demonstrated to be sensitive cellular targets in oxidant-induced lung injury, we evaluated the effects of a supplemental fatty acid on the lipid composition and oxidant susceptibility of pulmonary artery endothelial cells (PAEC) in monolayer culture. PAEC were incubated in culture medium supplemented with an ethanolic solution of 0.1 mM cis-vaccenic acid (CVA), an 18-carbon monounsaturated fatty acid, or with the ethanol vehicle alone for 3 h. Cells were then exposed to either control or oxidant (hyperoxia: 95% O2; or hydrogen peroxide: 100 microM) conditions. Oxidant induced cell injury was assessed by phase-contrast microscopy and by measuring the release of intracellular lactate dehydrogenase. Incubation with CVA increased the CVA content of PAEC lipids and protected cells from oxidant-induced injury for up to 72 h after supplementation. CVA had no effect on nonoxidant-induced cell injury. Although the mechanism by which CVA protects cells against oxidant injury remains undefined, evidence is presented that indicates the mechanism does not involve induction of antioxidant enzyme activity, alterations in the physical state of PAEC membranes, or enhancement of PAEC nucleic acid repair mechanisms. These results define a useful model for exploring the relationship between lipid composition and oxidant susceptibility and suggest that fatty acid modifications may constitute an important strategy for protecting cells against oxidant injury. PMID- 2223105 TI - Myofibroblasts and subepithelial fibrosis in bronchial asthma. AB - A thickened bronchial epithelial basement membrane has long been regarded as a histopathologic characteristic of bronchial asthma. As we had previously demonstrated that this phenomenon is due to the deposition of interstitial collagens and fibronectin, we have now sought to determine the nature of the cell responsible for this process by studying endobronchial biopsies from eight normal and seven asthmatic volunteers by immunohistochemistry and electron microscopy. Biopsies were stained with PR 2D3, a monoclonal antibody to myofibroblasts of the pericrypt sheath of the colon and a monoclonal antibody to alpha-smooth muscle actin. The thickness of the subepithelial collagen and the organelle content of the cells therein were determined by electron microscopy. The subepithelial collagen thickness in the normal subjects ranged from 2.16 to 6.26 microns, while that in the asthmatic subjects ranged from 3.75 to 11.1 microns (Mann-Whitney test; P = 0.05). Elongated cells in the collagen layer were identified by staining with PR 2D3. As this antibody also stains smooth muscle, consecutive frozen sections were stained for alpha-smooth muscle actin and the number of positive cells per millimeter of basement membrane was subtracted from the count for PR 2D3. This yielded a count of 4.9 to 9.4 cells/mm in the normal subjects and 11.9 to 20.6 cells/mm in the asthmatics (P = 0.001). There was a highly significant correlation between the depth of subepithelial collagen and the number of PR 2D3-positive, alpha-smooth muscle actin-positive cells (Spearman rank correlation; r = 0.764 and P = 0.006). Electron microscopy confirmed the myofibroblastic nature of these cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223104 TI - Human alveolar macrophage and blood monocyte interleukin-6 production. AB - Interleukin-6 (IL-6) modulates a number of processes relevant to host immunity and inflammation. We investigated the capacity of the human alveolar macrophage to elaborate IL-6 in response to lipopolysaccharide (LPS), recombinant interleukin-1 (rIL-1), and recombinant tumor necrosis factor (rTNF), and compared macrophage IL-6 production to that of blood monocytes and lung fibroblasts. Unstimulated and TNF-stimulated alveolar macrophages and monocytes produced little or no detectable IL-6. In contrast, macrophages and monocytes produced large amounts of IL-6 in response to LPS and monocytes produced lesser but readily detectable amounts in response to rIL-1. Monocytes and alveolar macrophages differed significantly in their capacity to produce IL-6, with macrophages making more IL-6 in response to LPS and less IL-6 in response to rIL 1 than autologous blood monocytes. Monocytes aged in vitro produced little detectable IL-6 in response to LPS or rIL-1, suggesting that differences in cell maturity may account for the diminished capacity of the alveolar macrophage to produce IL-6 in response to IL-1 but not its enhanced capacity to produce IL-6 in response to LPS. Mononuclear phagocytes and lung fibroblasts also differed in their ability to produce IL-6. Lung fibroblasts produced more IL-6 in response to rIL-1 and less IL-6 in response to LPS than monocytes and macrophages. In addition, monocytes and macrophages elaborated electrophoretically identical IL-6 moieties that differed from those produced by lung fibroblasts. These differences could be at least partially attributed to differences in sialylation and/or glycosylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223106 TI - The temporal bone: magnetic resonance imaging. AB - MRI has made a remarkable impact upon diagnostic evaluation of the temporal bone and its diseases. Although high resolution CT is preferable for study of common maladies of the middle ear and optic capsule, MRI is currently the study of choice for evaluation of the internal auditory canal, cerebellopontine angle, and brainstem. MRI is also very useful in evaluations of complications of chronic otitis media. This manuscript is divided into sections on inflammatory disease, internal auditory canal/cerebellopontine angle, vascular compartments, facial nerve, and trauma. In addition, several miscellaneous entities are discussed. PMID- 2223107 TI - Current status of magnetic resonance imaging of the orbit. AB - MR plays an important role in evaluating pathologic conditions that affect the orbit. MR appears to be superior to ultrasound and computed tomography in evaluation of intraocular tumors and fluid collections. In evaluation of noncalcified intraorbital tumors, MR can provide more information regarding orbital apex involvement and intracranial extension. Inflammatory lesions, particularly orbital pseudotumor, can be differentiated from metastatic disease based on differences in signal intensity providing greater specificity than CT. Specific prognostic information may be obtained regarding potentially treatable cases of Graves' disease. Using MR, vascular lesions of the orbit can be assessed for patency or thrombosis without use of intravenous contrast. Demonstration of secondary extension by para-orbital sinus tumors by MR is often helpful in evaluating involvement of the soft tissue structures of the orbit. Potential applications in evaluation of orbital trauma include characterization of orbital hematomas and orbital blow-out fractures. PMID- 2223108 TI - Magnetic resonance imaging of the paranasal sinuses. AB - MRI has been very helpful in evaluating tumors in the paranasal sinuses. MRI can differentiate retained secretions from tumors. The multiplanar capabilities of MRI are also very helpful in identifying tumor margins. Although a specific diagnosis can be suggested in most cases, demonstration of the extent of the disease and specifically the relationship to key surgical landmarks is more important. Structures of thin cortical bone are better seen with CT than MRI. For several reasons, CT is still the examination of choice for evaluation of the osteomeatal complex and inflammatory disease of the sinuses. PMID- 2223109 TI - Magnetic resonance imaging of the nasopharynx. AB - Imaging of the upper aerodigestive tract, mainly the nasopharynx and oropharynx, has always challenged the radiologist. It is clear that MRI has a leading role in the diagnosis and treatment planning of patients with diseases of the head and neck. This is especially true in the nasopharynx. Although improvements have been made in x-ray diagnosis through the years, subtle diagnoses have been difficult to make because of the variations in airway contour and the superimposition of areas of interest. CT allowed the deep soft tissue planes to be evaluated and provides a complement to the physical examination of the nasopharynx, oral pharynx, and skull base. MRI possesses many advantages over other imaging modalities. The ability to differentiate between inflammatory and neoplastic diseases is extremely important for tumor staging and patient management. At the present time it is not possible to predict the histology of a nasopharyngeal tumor, but the ability to differentiate between various histologic types would be of obvious importance. More experience is needed before this bridge can be crossed. PMID- 2223110 TI - Magnetic resonance imaging of the tongue and oropharynx. AB - In general, MRI produces superior soft tissue detail in evaluating the tongue and oropharynx than does CT. MRI is therefore considered the study of choice in this area. Lack of artifact from dental amalgam and beam hardening artifact from the mandible on MRI also eliminates two major shortcomings of CT in the examination of this area. Finally, the ability of MRI to obtain direct coronal and sagittal scan planes is a distinct advantage in recognizing intrinsic tongue musculature and assessing tumor volume and spread for treatment planning. PMID- 2223111 TI - Magnetic resonance imaging of the larynx. AB - The development of appropriate surface coils has resulted in outstanding depiction of the laryngeal anatomy using MRI. The multiplanar capability of MR allows superior definition of anatomy and tumor extent compared with CT scanning. MR appears to be more effective in detecting cartilage invasion. MR is as effective as CT in defining adenopathy and extension into the carotid sheath. MRI is therefore the primary modality in imaging the larynx. PMID- 2223112 TI - Magnetic resonance imaging of metastatic cervical adenopathy. AB - Detecting cervical adenopathy is critical in the management of carcinomas in head and neck. CT scanning remains a very effective modality in defining adenopathy. T1-weighted MRI scans are comparable to CT in detecting lymph nodes. T2-weighted images are less useful as the lymph nodes tend to have long T2 relaxation times similar to the surrounding fat. MR has not proved to be useful in detecting carcinoma in non-enlarged cervical nodes. The morphologic criteria developed for metastatic nodes with CT are appropriate with MRI (size, shape, signal, extracapsular spread). Gadolinium is sometimes useful in defining central necrosis in metastatic squamous cell adenopathy. PMID- 2223113 TI - Interventional magnetic resonance imaging in the head and neck. AB - Interventional MRI is clearly in its early stages of development. While the value of MR-guided aspiration cytology and MR evaluation of deep electrode implantation in the brain has already been confirmed with human clinical studies, the future of MR-guided interstitial laser therapy remains to be proven. Despite this, as we look ahead into the 1990s and the millennium, it is possible to imagine dedicated MR laser therapy units for combined radiological and surgical outpatient approaches in what may become the operating rooms of the 21st century. PMID- 2223114 TI - Congenital cystic adenomatoid malformation of the lung. AB - Twenty cases of cystic adenomatoid malformation of the lung were observed: 2 had died in utero; the diagnosis was made at birth in 13 infants of which 3 were premature. A Bochdalek's hernia had been diagnosed before birth in 2 cases by echo-tomography. The correct antenatal diagnosis had been made in 2 cases. Two infants had no symptoms, 3 were dyspneic, 8 were in respiratory distress and had to be intubated and ventilated. Two had a prune belly syndrome. Eight infants had a thoracotomy during their first week of life. Pulmonary resections concerning those 13 patients comprised 10 lower lobectomies, 1 of which was associated with a lingulectomy, and 2 upper lobectomies, 1 of which was associated with a middle lobe resection. Five patients were diagnosed and operated upon between 10 months and 8 years of age; 4 had recurrent bronchitis and 1 was diagnosed during the treatment of a gastroenteritis. They had 3 lower and 2 upper lobectomies. Recovery was uneventful in all patients except for 1 who was reoperated upon for intestinal obstruction. Antenatal diagnosis of cystic adenomatoid malformation should become standard. The malformation may be mistaken for a pulmonary sequestration or bronchogenic cyst. Differential diagnosis of a congenital hernia is important. PMID- 2223116 TI - Patch-closure of tracheal defects with pericardium/PTFE. A new technique in extended pneumonectomy with carinal resection. AB - Patch closure of a tracheal defect resulting from extended pneumonectomy including the main carina and a limited area of the lower trachea or the opposite bronchus is described in five cases of bronchogenic carcinoma and one case of metastatic melanoma. It was accomplished by the use of a PTFE soft-tissue patch and integrated pericardial flap. Airway continuity was satisfactorily restored in all but one case with a longest survival of 30 months. One patient developed an empyema and died from respiratory failure after 6 weeks. The method is technically easy and can serve as an alternative to resection of the whole bifurcation in selected cases. Intraoperative ventilation using double lumen tubes needs not be altered. PMID- 2223115 TI - Pulmonary complications after lung resection: the effect of continuous extrapleural intercostal nerve block. AB - To assess the efficacy of continuous extrapleural intercostal nerve block (CEINB) with 0.5% bupivacaine on postoperative pain, pulmonary function and pulmonary complications, a prospective, randomised, double blind controlled trial was conducted on comparable patients undergoing lung resections; n = 21 (control), n = 25 (bupivacaine). The bupivacaine group required less papaveretum in the first 24 h (P less than 0.01) and had lower pain scores over 5 postoperative days (P less than 0.01). Pulmonary function recovered earlier in the bupivacaine group. Pulmonary complications occurred in 1 patient with normal lung function and 12 patients with obstructive airways disease (COAD): FEV1/FVC less than 70%. There were no infusion-related complications. CEINB has been shown to be safe and effective in reducing postoperative pain and pulmonary complications. CEINB minimises the loss of lung function after thoracotomy and restores impaired pulmonary mechanics more rapidly. PMID- 2223117 TI - Thoracic injuries sustained by the survivors of the M1 (Kegworth) aircraft accident. The Nottingham, Leicester, Derby, Belfast Study Group. AB - On 8 January 1989, a Boeing 737 carrying 126 passengers and crew crashed onto the M1 motorway killing 39 passengers. Of 87 initial survivors, 74 had major injuries making this an unusual accident as most aircraft crashes result in very few severely injured survivors. This prompted the setting up of a major study group, the Nottingham, Leicester, Derby, Belfast Study Group (NLDB) to examine in detail the accident and its aftermath. This paper is part of that work and is an initial survey of the thoracic injuries sustained by the 87 survivors. Twenty-three passengers sustained major chest trauma and all had major injury to other parts of the body. Five of these patients died within 12 h of admission. Various patterns of chest trauma emerged from this study, including an increasing incidence of rib fractures with age and a distinctive pattern of upper zone pulmonary contusion in younger patients. PMID- 2223118 TI - Risk factors for morbidity and mortality in mitral valve replacement. AB - Risk factors of operative mortality and long term survival were identified in 219 patients who underwent mitral valve replacement (MVR) using Bjork-Shiley mechanical prostheses. Early mortality was 7.3%. The accumulated follow-up time was 1134 patient-years, and the 5-year survival for the total cohort was 78 +/- 3%. Independent prognostic factors of early mortality were poor NYHA class, which carried a relative risk (RR) of 3.2, and ischaemic aetiology, with a RR of 2.2. Ischaemic aetiology was the sole predictor of heart pump failure requiring intra aortic balloon pump support (RR = 2.7). Independent risk factors of total mortality (early and late) were male sex (RR = 2.3), NYHA class III-IV (RR = 2.4), presence of mitral regurgitation (RR = 3.2) and relative heart volume (RR = 1.6 for a 800 ml/m2 size compared to a heart of 550 ml/m2). Our results underline the importance of patient-related factors in MVR, and indicate that care is needed in comparing the quality of MVR from different institutions with respect to mortality and morbidity. The results of MVR are palliative rather than curative except in female patients with NYHA class II function and mitral stenosis, in whom cure was attained. PMID- 2223119 TI - Morphological comparison of primary tissue failure (PTF) in porcine mitral and aortic bioprostheses in the same patient. AB - Clinical and pathological studies have not clearly demonstrated whether primary tissue failure (PTF) in porcine bioprostheses occurs more often in the mitral than in the aortic position. We have studied morphological alterations in both positions in the same individual in 15 patients (14 mitroaortic and 1 mitroaortotricuspid) reoperated upon for PTF. Bioprostheses explanted were photographed, radiographed and observed in transmitted polarizing light. All lesions received a score on the basis of morphological criteria. The creep of the stent was measured. Calcification was slightly heavier and the degree of creep was significantly greater in the mitral position. Tears, infiltration and pannus growth did not differ between the two positions. According to our study, there is no conclusive demonstration that bioprostheses degenerate earlier and more extensively in the mitral than in the aortic position. PMID- 2223121 TI - The effects of low, medium and high dose aspirin on intimal proliferation in autologous vein grafts used for arterial reconstruction. AB - Bilateral femoral vein grafts were implanted in 47 adult mongrel dogs to determine the effects of aspirin on intimal hyperplasia. The animals were fed a commercially-prepared 2% cholesterol diet before and for 6 weeks following operation. Twelve animals served as the controls while the remaining animals were divided into three groups receiving low, medium, and high dose aspirin. Eleven animals received 75 mg of aspirin daily, 11 animals were fed 225 mg of aspirin daily and the remaining 13 animals received 650 mg of aspirin daily. A coagulation profile was carried out before operation and at 2, 4 and 6 weeks following operation. The grafts were harvested at 6 weeks and intimal thickness was measured with a Zeiss computerized interactive image-analyzing system. The prothrombin time, partial thromboplastin time, and platelet count were unchanged in all animals. The bleeding time was prolonged in animals receiving aspirin (P less than 0.02). Intimal thickness measured 4 +/- 0.2 microns before implantation and increased at 6 weeks to 39 +/- 5 microns in the control group. Aspirin failed to reduce intimal hyperplasia. Intimal thickness measured 37 +/- 2 microns in those animals receiving 75 mg of aspirin daily, 35 +/- 3 microns after a daily dose of 225 mg of aspirin and 51 +/- 4 microns in the high dose group receiving 650 mg of aspirin daily. Our data indicates that aspirin fails to reduce intimal proliferation in canine vein grafts which suggests that alternative or combined drug therapy may be necessary to reduce the incidence of late graft failure. PMID- 2223120 TI - Differences in the recovery of right and left ventricular function after ischaemic arrest and cardioplegia. AB - Differential susceptibility of right (RV) and left (LV) ventricles to plain ischaemia and the contribution of cardioplegia in reducing the ischaemic damage was evaluated in a sheep model of cardiopulmonary bypass. Sheep (n = 16) were equally divided for the two protocols of the study. Each sheep served as its own control. RV and LV functions were studied and compared by plotting ventricular function curves (Starling and Sarnoff). The mathematical centre of mass (COM) for each curve was computed by a polynomial regression program. The COM values of the contractility indices [stroke volume (SV), stroke work (SW)] represented ventricular heterometric reserve. RV and LV heterometric reserve was significantly (P less than 0.01) reduced after 1 h plain ischaemia, and quantitatively this change was more for RV than for LV (P less than 0.05). As compared to LV, a significantly greater reduction in RVSW was brought about by a significantly (P less than 0.01) greater reduction in RVSV, because there were no significant differences between the post-ischaemic recovery in the RV and LV afterloads. Cardioplegic protection nearly normalized filling pressure and contractility (SV, SW) of both ventricles, but major differences were observed in the recovery of compliance. Recovery in the RV compliance exceeded the control values, and quantitatively the recovery in RVSW was slightly more than in LVSW. The results of this study indicate that the RV suffers more damage from plain ischaemic arrest and hence benefits more from the cardioplegic protection. PMID- 2223122 TI - Epicardial cryosurgery as used in ablation of accessory atrioventricular pathways: effect on valvular function in the dog. AB - Epicardial cryosurgery for ablation of atrioventricular accessory pathways has surgical advantages. However, it is applied directly to the valve base. To assess the risk of valve impairment, 10 anaesthetized dogs were subjected to standardized epicardial cryosurgery of the right atrioventricular junction. Two of these underwent sham procedure (dissection only). Valve function was assessed by colour Doppler echocardiography preoperatively and at 2 days, 1 week, 2 weeks and 10 weeks postoperatively. Three out of the eight animals subjected to cryosurgery developed moderate (grade 2/4) tricuspid insufficiency, which appeared at 1 week postoperatively, following regression of congestive oedema. Two out of the three cases of TI were associated with leaflet prolapse. No tricuspid insufficiency was seen in the sham-operated animals. At the end of each interval two animals were killed for histological examination. Histological examinations showed that cryolesions extended a maximum of 3 mm into the valve leaflet. The tricuspid insufficiency is attributed to the extensive scarring (including chondroid metaplasia), which causes retraction and restricted motion of the annulus. It is concluded that cryolesions may impair atrioventricular valve function. Patients undergoing cryosurgery should be monitored postoperatively by echocardiography for atrioventricular valve insufficiency. PMID- 2223123 TI - Congenital bronchoesophageal fistula in adults. Report of three cases. AB - Persistence of congenital bronchoesophageal fistulae into adulthood is rare. Three patients, one male and two female, of 52, 27 and 63 years of age, respectively, are reported. All three presented with chronic respiratory symptoms and coughing spells associated with ingestion. The barium swallow confirmed diagnoses. Treatment was surgical and consisted of excision of the fistulous tract, suture of the oesophageal and bronchial orifices and the interposition of a parietal pleura flap in two cases, and of biological glue in one. All three patients recovered and are free of symptoms. PMID- 2223124 TI - Intramural oesophageal cyst as a cause of acute respiratory distress. AB - A case is reported of an intramural oesophageal cyst. Acute dyspnoea, due to compression of the trachea, was an indication for exploratory sternotomy. PMID- 2223125 TI - Anatomically guided surgery to the AV node. AV nodal skeletonization: experience in 46 patients with AV nodal reentrant tachycardia. AB - We report our combined experience with operative therapy for atrioventricular nodal tachycardia using an anatomically guided procedure. The operative rationale was to dissect the AV node with the intent of modifying perinodal tissues (skeletonization). The anterior septal and posterior septal regions were initially approached epicardially to facilitate endocardial dissection. Under normothermic cardiopulmonary bypass, the right atrial septum was mobilized and the intermediate AV node was exposed anterior to the tendon of Todaro. Ablation of concomitant accessory pathways was done prior to AV nodal skeletonization. Forty-six patients aged 9-71 years (mean 36) were operated upon. Five patients had accessory pathways in addition to AV nodal reentry. At electro-physiological study prior to discharge, no patient had an AV block although anterograde and retrograde Wenckebach cycle lengths were significantly prolonged. Ten patients had a retrograde AV block. The 46 patients were free of arrhythmia and not taking antiarrhythmic medication after a follow-up of 1-45 months (mean 17). Three patients had a recurrence of the tachycardia 10 days, 2 months and 7 months post operatively, respectively. All patients had a subsequently successful reoperation. PMID- 2223126 TI - Surgical treatment of chronic aortic dissections. AB - Between January 1976 and March 1987, 78 patients underwent surgery for chronic aortic dissection at our institution. The ascending aorta was involved in 66 cases (Stanford type A) and was not involved in 12 cases (Stanford type B), wherever the initial dissection was suspected. Aortography remains the main preoperative investigation. The surgical technique varies according to the type of dissection. It seems essential to exclude the primary intimal tear and all dilated segments of the aorta must be replaced. The overall operative mortality was 11.5% (7.5% in type A, 33.3% in type B dissection). Sixty-three patients have been followed for a period varying between 6 months and 10 years (mean 5 years). The overall survival at 6 years is 60% +/- 5.6%. Because of the ultimate risk of aneurysmal dilatation of the false channel, these patients must be followed by CT scanning, colour flow Doppler echocardiography, magnetic resonance imaging, and in some cases, aortography. PMID- 2223127 TI - Median sternotomy and multiple lung resections for metastatic sarcomas. AB - In the attempt to apply salvage surgery to the majority of patients with pulmonary tumour relapse, we have adopted a new treatment plan consisting of early bilateral lung exploration and resection through median sternotomy in all cases of sarcoma with resectable lung metastases, including synchronous or previously resected ones. The present paper summarizes the early results achieved with this technique in 56 consecutive patients treated between 1985 and 1988. Perioperative mortality was zero, and morbidity negligible. Occult contralateral metastases were resected in about one third of subjects with monolateral clinical lesions. Overall actuarial survival from first pulmonary resection is 51% at 2 years and 35% at 3 years. A slightly more favourable trend is evident for solitary lesions but the difference is not statistically significant. No difference in survival is observed in relation to the initial disease-free interval or to the histological type. The majority of relapses occurred within 6 months of sternotomy (23/35) and were confined to the lungs (21/35). Ten of these 21 patients with pulmonary relapse have undergone further resection and 5 of them are alive, with a median survival of 28 months. Present results are encouraging as far as resectability and early recurrence rate are concerned. Median sternotomy appears a most valuable therapeutic approach to pulmonary metastases from sarcomas, being safe and effective in local control of disease, and compatible with further surgical management of pulmonary recurrences. PMID- 2223128 TI - Coarctation of the aorta in complex congenital heart disease: simultaneous repair via sternotomy. AB - Coarctation of the aorta (CoA) is often associated with complex congenital heart disease. Patients with such a combination may not benefit from coarctectomy alone. Eight children who presented with complex malformations of the heart underwent simultaneous repair of CoA and intracardiac surgery via sternotomy. After extensive mobilization of the aortic arch, cardiopulmonary bypass was established. During the cooling phase for deep hypothermic circulatory arrest (six cases), a persistent temperature gradient between the upper and lower half of the body confirmed the significance of CoA. One child was operated upon in deep hypothermia with low flow and one underwent valve repair on cardiopulmonary bypass. Mobilization of the descending aorta enabled CoA resection and end-to-end anastomosis with a running absorbable suture. The average descending aortic cross clamping time was 15 min. By this time, the patient had been cooled sufficiently for the intracardiac procedure. There were two operative deaths not related to coarctectomy. The remaining children showed no arm-to-leg pressure gradient. Five were discharged from hospital and one patient died late from septicaemia. In our hands, this technique has served to accomplish simultaneous relief of CoA and repair of the intracardiac lesion thus sparing critically ill infants the hazards of repeated procedures. PMID- 2223129 TI - Paralysed diaphragm after cardiac surgery in children: value of plication. AB - Over a 2-year period (1987-1988), 31 children (3% of 960 operations) were found to have a paralysed diaphragm following cardiac surgery. The median age was 5 months with 65% less than 1 year of age. In the 31 patients, 38 paralysed diaphragms were identified. The phrenic nerve injury was on the right in 8 cases, the left in 16, bilateral in 7 and 40% were related to modified Blalock Taussig shunts. The time to extubation was analysed for each patient in two separate groups: Group A: (greater than 1 year): 11 children of whom 5 were extubated without difficulty, 4 had non-respiratory reasons for prolonged ventilation and only 2 were plicated--both were extubated within 4 days. Group B: (less than 1 year): 20 infants of whom 16 were plicated and 4 were not. Three of the children who were plicated died from cardiac causes. Of the 13 survivors, there were 3 who had other reasons for prolonged ventilation. Thus 10 infants required prolonged ventilation (mean 11 days) because of respiratory difficulties. All underwent plication and were extubated at a mean of 2.4 days postoperatively. The 4 who were not plicated were extubated at a mean of 11 days postoperatively. In infants in whom there is no cardiac cause for failure to wean from ventilation, diaphragmatic paralysis should be suspected and plication performed if not extubated 2 weeks after operation. PMID- 2223130 TI - Age-dependent changes in the tolerance of the rabbit heart to ischemia. AB - Many studies in several species have demonstrated an enhanced ischemic tolerance in the immature myocardium when compared with the adult. Little is known about the rate at which these changes occur. We have compared the extent of post ischemic recovery using isolated working hearts from rabbits of various ages (7 90 days). Hearts (n = 8/group) from rabbits of 7, 14, 21, 28, 31, 40 and 60-90 days of age were perfused aerobically (37 degrees C) for 20 min and control indices of cardiac function were recorded. The hearts were then arrested (2 min infusion) with the St. Thomas' Hospital cardioplegic solution and subjected to global ischemia for 45 min (37 degrees C). The hearts were then reperfused for 15 min in the Langendorff mode and 20 min in the working mode. Leakage of creatine kinase (CK) during Langendorff reperfusion and the recovery of cardiac function during working perfusion were measured. Pre-ischemic cardiac output (CO) was 58.6 +/- 2.6, 80.1 +/- 2.9, 117.5 +/- 4.5, 131.9 +/- 3.2, 134.1 +/- 2.1, 152.0 +/- 1.6 and 165.8 +/- 4.6 ml/min in the 7, 14, 21, 28, 31, 40 and 60-90 day-old groups, respectively. Following ischemia, CO recovered to 82.9 +/- 3.6, 79.2 +/- 3.1, 77.9 +/- 3.4, 72.3 +/- 2.7, 55.3 +/- 2.1, 35.7 +/- 2.9 and 33.1 +/- 6.9%, respectively. CK leakage correlated poorly with recovery and was 31.5 +/- 4.7, 32.0 +/- 8.5, 33.6 +/- 7.9, 35.8 +/- 7.0, 37.3 +/- 4.4, 38.7 +/- 4.8 and 30.4 +/- 5.9 IU/15 min per gram dry weight, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223131 TI - Canine heart-lung transplantation after 24-hour hypothermic preservation. AB - We compared the efficacy of Belzer UW solution (UWS) with modified Collins solution (MCS) in a 24 h canine heterotopic heart-lung transplantation model. Nine pairs of mongrel dogs were divided into 2 groups: MCS group (n = 5) and UWS group (n = 4). The donor heart was arrested with cardioplegia. The heart and lung were flushed with MCS or UWS, excised en bloc and immersed in 4 degrees C MCS or UWS for 24 h. Graft function was adequate in 1 of 5 grafts in the MCS group and in all 4 grafts in the UWS group (P less than 0.05). In the UWS group, the prepreservation and posttransplantation cardiac output was 71.2 +/- 21.6 and 96.4 +/- 44.4 ml/min per kg, the PaO2 was 80.8 +/- 12.9 and 74.1 +/- 2.7 mmHg, and the PaCO2 was 25.6 +/- 5.5 and 35.9 +/- 13.3 mmHg, respectively. No difference was significant. In the UWS group, the pulmonary vascular resistance increased significantly to 13.8 +/- 3.7 from 8.8 +/- 5.2 Wood units (P less than 0.05). Post-transplantation myocardial water content in the UWS group (78.6 +/- 2.0) was less than in the MCS group (81.1 +/- 1.4, P less than 0.05). The wet/dry ratio of the lung increased significantly to 8.3 +/- 1.6 from 4.4 +/- 0.6 in the UWS group (P less than 0.01) and to 10.3 +/- 0.8 from 4.1 +/- 0.1 in the MCS group (P less than 0.01), but was less in the UWS group (P less than 0.05). These results suggest that UWS is more effective than MCS in 24 h heart-lung preservation, but does not prevent pulmonary oedema adequately. PMID- 2223132 TI - Myocardial revascularization without extracorporeal circulation. Seven-year experience in 593 cases. AB - The authors present the results of 593 consecutive and non-selected patients who underwent direct myocardial revascularization without extracorporeal circulation in the period September 1981 to December 1988. The results are compared with 3086 patients who underwent conventional bypass surgery over the same period of time. The ages varied from 33 to 80 years (mean = 56) with 40 patients older than 70. The overall mortality in the group without cardiopulmonary bypass (CPB) was 1.7% (10/593) compared with 3.8% for conventional revascularization. Our mortality in the last 3 years has been 0.5% and 0% in the last 203 patients revascularized without CPB. The number of grafts varied from 1 to 5 (average 1.6). The treated arteries were: anterior descending (557), right (282) marginal (5) and circumflex marginal (4). Immediate postoperative complications were fewer and hospital discharge was earlier in the group treated without CPB. The authors conclude that this tactical alternative has the advantages of: lower morbidity and mortality, lower cost and no need for blood transfusion. Drawbacks are the need for greater technical expertise and it seems to be possible in about 19% of all patients who undergo myocardial revascularization. PMID- 2223133 TI - Coronary surgery without extracorporeal circulation: benefit or additional risk for the patient? PMID- 2223134 TI - Patency of arm vein grafts used in aorto-coronary bypass surgery. AB - Arm veins have been used in myocardial revascularisation procedures as a last resort bypass conduit because of their associated low patency. Nevertheless, leg veins and mammary arteries, which are the most commonly used, are sometimes not sufficient, leaving little choice as to the bypass conduit. To assess the properties of arm veins in bypass surgery, we compared a group of 28 patients that underwent an arm vein graft coronary bypass procedure with a matched group of patients in which leg veins were used. In 28 patients, 40 arm vein grafts with 77 distal anastomoses were used (mean 1.9 +/- 0.9; range 1-5). A cerebrovascular accident was the cause of the sole death (2%) during the study period. The mean follow-up was 4.6 years (Standard deviation, SD: 1.5 years). More antianginal medication was used in the arm vein group (P = 0.017). Additionally, the percentage of the expected maximal frequency during exercise testing was lower in the arm vein group as compared to the leg vein group. Digital subtraction angiography showed that the patency of the arm vein bypass grafts was 47% (70% confidence limits, CL: 32%-62%) while the patency of the leg vein grafts was 77% (CL: 64%-87%), which was statistically significant (P = 0.051). Comparison of these figures with the few published reports on arm veins used as coronary bypass grafts reveals similar results. We conclude that the arm vein as a coronary bypass graft is only to be used when mammary arteries and leg veins are not available. PMID- 2223135 TI - Type 1 aortic dissection with right coronary artery occlusion and fistula to right atrium and right ventricle. AB - A fistula between the aorta and right atrium which communicates with the right ventricle is an extremely rare and rapidly lethal complication of aortic dissection. There are only three previously reported cases of survival after operative repair of aorto-right atrial fistulae in the literature. We describe a patient who experienced acute aortic dissection with fistula formation to the right atrium and to the right ventricle. The patient underwent successful operative repair. PMID- 2223136 TI - False passage in the interventricular septum. Echocardiography in diagnosis and management of a rare complication after closed transventricular valvotomy for critical aortic stenosis. AB - A case of a false passage causing an aneurysm of the interventricular septum is reported. Two-dimensional echocardiography facilitates the correct preoperative diagnosis of critical aortic stenosis and is helpful in the postoperative management to assess the outcome and detect complications. Surgical intervention for a false passage was prevented by serial echocardiographic follow-up studies showing resolution of the aneurysm. PMID- 2223137 TI - The theoretical implications and experimental and clinical results of radiolabeled antiferritin. AB - Ferritin is produced in malignant and normal tissues. It acts both as an immunosuppressant and as an iron storage protein. As a tumor associated protein, it is related to virally induced tumors, and selective tumor targeting by radiolabeled antiferritin antibodies has led to its use in clinical trials. In patients with advanced Hodgkin's disease who have failed conventional therapy, 131I antiferritin produced partial remissions, while 90Y antiferritin led to complete remissions and a demonstrable dose-response relationship. Combining the variable low-dose radiation patterns produced by radiolabeled antibody therapy with chemotherapy in the treatment of hepatocellular cancer has led to enhanced tumor cytotoxicity and, in some cases, the conversion of non-resectable hepatoma to resectable. Further, the potential for clinical and laboratory investigation of radiolabeled antibody therapy is discussed in light of new findings. PMID- 2223138 TI - The role of adjuvant chemotherapy in the treatment of advanced head and neck cancer. AB - The role of chemotherapy in the multidisciplinary treatment of advanced squamous cell carcinoma of the head and neck remains to be defined. Uncontrolled adjuvant studies integrating chemotherapy with local therapies utilizing a 'sequential' or 'simultaneous' strategy have indicated that high response rates to initial chemotherapy and high complete remission rates are achievable. Both these factors appear to predict for improved survival. Unfortunately results of randomized, controlled studies generally have not confirmed any major overall survival advantage. However, these trials clearly failed to utilize optimal therapies: suboptimal trials yield suboptimal results. Encouraging data from large uncontrolled studies have now provided critical information regarding optimal trial design; a) Since primary tumor site has proved a significant predictive factor for response to treatment and survival, future trials must include sufficient numbers of patients for detailed site-by-site analyses, and b) radical surgery may be omitted without compromising survival by using initial chemotherapy followed by radiotherapy for advanced laryngeal cancer. PMID- 2223139 TI - The association between risk of breast cancer and age at first pregnancy and parity in Maribo County, Denmark. AB - The effect of age at first pregnancy and number of pregnancies was examined in a cohort of 14,421 women where reproductive informations were collected as part of a cervical cancer screening program. A total of 352 cases occurred in the cohort. In subgroups of women defined by age at first pregnancy the relative risk of breast cancer was lower among women who were first pregnant before 25 years of age (RR = 0.85 vs 1.20). In subgroups of women defined by parity the relative risk decreased with increasing number of pregnancies from about unity among women with 0-3 pregnancies to 0.7 among women with 6 or more pregnancies. PMID- 2223140 TI - Simple mastectomy with postoperative irradiation versus extended radical mastectomy in breast cancer. A twenty-five-year follow-up of a randomized trial. AB - From November 1951 to December 1957, all patients with untreated breast cancer admitted to the Radium Centre in Copenhagen were randomized before their operability was evaluated into two groups, if the patients were operable, viz. simple mastectomy with postoperative x-ray treatment or extended radical mastectomy. Twenty-five-year results are presented, showing no difference in survival or recurrence-free survival of the operable patients. Histological grading was performed in nearly all cases. Patients with grade 1 tumours had a better survival than grades 2 and 3, but there was no difference in survival between the two treatment groups, when histological grading was taken into account. Histological node positive patients had more grades 2 and 3, tumours, whereas node negative patients had more grade 1 than grades 2 and 3 tumours. Premenopausal women had a significantly better survival than postmenopausal in all stages. PMID- 2223142 TI - Axillary sampling and the risk of erroneous staging of breast cancer. An analysis of 960 consecutive patients. AB - Axillary nodal status was analysed in 960 consecutive cases of primary invasive breast cancer operated in two Danish hospitals. After stratification according to the number of nodes removed, the rate of node positivity in each subgroup was calculated. We found that the probability of finding at least one metastatic node increased continuously up to about 10 removed nodes. In lymph node negative patients, who did not receive any adjuvant treatment, there was a significant association between the recurrence-free survival and the number of nodes removed, provided that less than 8-10 nodes had been collected. The percentage of node positivity in each subgroup seemed to level off above 10 nodes at about 64%, suggesting that this represents the true rate of node positivity at the time of primary surgery. We conclude that about 10 axillary nodes should be removed in order to minimize the risk of erroneous classification of the axilla. PMID- 2223141 TI - Second line hormonal therapy with aminoglutethimide in metastatic breast cancer. AB - One hundred and twenty patients with metastatic breast cancer, whose disease progressed on hormonal therapy with tamoxifen, were treated with aminoglutethimide. The overall response rate was 34% and the median duration of response 9.5 months. Response to aminoglutethimide was achieved in all metastatic sites except lung and brain. Even 25% of patients who had failed to respond to prior tamoxifen did respond objectively to aminoglutethimide. The actuarial survival for all patients at 30 months was 22%. Although initial toxicity was high (70%), side effects of aminoglutethimide were transient, and treatment had to be discontinued in only four patients. The results of this trial confirm that aminoglutethimide is an effective treatment in metastatic breast cancer. PMID- 2223143 TI - Oral versus intravenous melphalan and prednisone treatment in multiple myeloma stage II. A randomized study from the Myeloma Group of Central Sweden. AB - Eighty-one previously untreated patients with multiple myeloma stage II entered a randomized trial comparing oral melphalan (0.25 mg/kg/day; n = 40) with intravenous melphalan (0.125 mg/kg/day; n = 41) in combination with oral prednisone (2 mg/kg/day). The courses were given for 4 days and repeated every sixth week. The treatment groups were well comparable with regard to major prognostic factors. There was no statistically significant difference in the response rates, the response duration times and the survival times. No significant difference in nonhematological and hematological toxicity was noted. Since intravenous administration of melphalan did not result in a substantial increase in response rate or survival, this study supports the use of oral melphalan/prednisone as first-line therapy for patients with multiple myeloma. PMID- 2223144 TI - Non-Hodgkin's lymphoma. A four-drug regimen suitable for elderly patients with advanced disease. AB - Twenty-eight patients with non-Hodgkin's lymphomas considered unsuitable for doxorubicin containing combination chemotherapy were given the four-drug combination chlorambucil, mitoxantrone, procarbazine and prednisolone every 3 weeks. The median age of the patients was 69 years and 15 had received prior treatment. Non-haematological toxicity was WHO grade I or II in all cases. Five patients had grade 4 neutropenia of which 3 were associated with fever and one was fatal. The complete response rate was 32% and the overall response rate 61%. The actuarial survival of the 17 responding patients at 12 months was 68%. This outpatient regimen produced good compliance among elderly patients, and modest toxicity with acceptable response rate and survival for the study population. PMID- 2223145 TI - Carcinoma of the uterine cervix treated by irradiation alone. Results of treatment at the National Cancer Center, Tokyo. AB - Six hundred and twelve patients with previously untreated invasive carcinoma of the uterine cervix were treated by irradiation alone at the National Cancer Hospital from 1972 to 1983. The number of patients was 7, 39, 43, 127, 15, 319, 28 and 34 in stages IA, IB, IIA, IIB, IIIA, IIIB, IVA and IVB respectively. Low dose-rate intracavitary irradiation with or without external irradiation was used in 383 patients, high-dose-rate intracavitary irradiation with or without external irradiation in 130, external irradiation alone in 98, and external irradiation combined with radon-222 seed implantation in one patient. Five-year survival rates were 85, 65, 57, 41, 14 11% for stages IB, IIA, IIB, IIIB, IVA, and IVB respectively. The rate of complications was rather high in the present series, and so we have been investigating whether it is possible to reduce the dose. Low-dose-rate intracavitary irradiation has been replaced by high-dose-rate irradiation by using a remotely controlled afterloading system. PMID- 2223146 TI - Microphotometric DNA analysis in moderate dysplasia of the uterine cervix. Correlation to the progression and regression of the lesion. AB - Nuclear DNA content was determined by microphotometry in 27 cases of moderate dysplasia of the uterine cervix. All these cases were followed from one to ten years to study the biological behavior of moderate dysplasia in relation to cervical carcinogenesis. Ten of them showed progression to carcinoma in situ during a period of one to six years (median 34.8 months) and 17 cases showed regression to inflammation and normalcy during a period of one to ten years (median 44.2 months). DNA analysis was performed both on initial cervical smear and on representative smears collected during follow-up. Amongst ten cases which progressed to malignancy, nine had aneuploid DNA pattern and one had polyploid DNA pattern throughout the follow-up period. Amongst 17 cases which regressed to inflammation, 11 had euploid and six polyploid DNA pattern. The observation that moderate dysplasia with aneuploid DNA value often develops into carcinoma in situ in contrast to dysplasia with euploid or polyploid DNA value strengthens the conception that DNA aneuploidy may be considered as 'high risk indicator' for cervical precancerous lesions. PMID- 2223147 TI - Microscopic and flow cytometric study of micronuclei in iododeoxyuridine labelled cells irradiated with soft x-rays. AB - Iododeoxyuridine labelled (IUdR(+)) and unlabelled (IUdR(-)) CHO cells irradiated with 2 Gy of soft x-rays showed only minor differences in the kinetics of micronuclei formation during the first 20 hours postirradiation period. Between 20 to 40 hours, the IUdR(-) cells showed approximately a constant number # of micronuclei while the number of micronuclei in IUdR(+) cells was still increasing. The frequency of micronuclei was higher in IUdR(+) cells compared to IUdR(-) cells at 24 hours after irradiation with various doses up to 4.0 Gy. Dose modifying factors were found to be 1.3 (microscopic evaluation) and 1.8 (flow cytometric evaluation). Flow cytometry with use of two parameters, fluorescence from propidium iodide and light scattering, seems to be a good tool to estimate the frequency of micronuclei in CHO cells in the dose range up to about 4 Gy. At higher doses perturbation of the cell cycle and the appearance of dying cells will influence the results. PMID- 2223148 TI - The in vivo response of a C3H mammary carcinoma to treatment with misonidazole, cyclophosphamide and radiation. AB - The potential chemosensitizing effect of the nitroaromatic radiosensitizer misonidazole (MISO) on the alkylating agent cyclophosphamide (CTX), and the interactions of these agents with radiation, have been investigated in a C3H mammary carcinoma in CDF1 mice. MISO at 1,000 mg/kg caused a small increase in tumour growth time (TGT; time to reach 3 times treatment volume) from 3.6 days to 4.5 days. CTX (100 mg/kg) increased the TGT to 15.7 days. The combined treatment of MISO and CTX given with intervals of either 15 min or 4 h increased the TGT to 23.3 and 23.8 days respectively. The radiation enhancement ratio (ER) was found to be 2.13 and 1.10 for MISO administered before or after x-rays respectively. The corresponding ERs for CTX were 1.16 and 1.22. The two drugs given in combination resulted in significant radiation ERs of 2.68 (both drugs given within 30 min before x-rays), 3.00 (MISO 30 min before and CTX 3 1/2 h after x rays) and 1.40 (both drugs given after x-rays). In contrast to what has previously been reported, and in contrast to the tumour regrowth delay data, the results of the tumour control experiments were found to reflect no more than an additive action of the two drugs when used together with radiation in vivo. PMID- 2223149 TI - Melatonin and immunity. PMID- 2223150 TI - Prostatic acid phosphatase in cloacogenic carcinoma. PMID- 2223151 TI - Influence of bestatin on production of granulocyte-macrophage colony-stimulating factor from human peripheral blood mononuclear cells in vitro. AB - Bestatin, (25, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine, enhanced proliferation of normal human bone marrow granulocyte-macrophage progenitor cells to form CFU-GM colonies in viscous methylcellulose medium in vitro. To elucidate the mechanisms of this effect, the levels of colony-stimulating factor (CSF) in culture supernatant of 1 x 10(6)/ml peripheral blood mononuclear cells (PBMC) cocultured with various concentrations of bestatin were determined using our newly developed sandwich enzyme-linked immunosorbent assay (ELISA). The level of granulocyte/macrophage-CSF (GM-CSF) in the supernatant in the presence of 0.1 microgram/ml bestatin was 312 pg/ml by this ELISA. The production of GM-CSF increased with increasing amounts of added bestatin. PMID- 2223152 TI - Inhibitory effect of bestatin on the growth of human leukemic cells. AB - We examined the effect of bestatin (Ubenimex) on the growth of human leukemic cells (i.e, HL-60, K562, MT-1, MT-2, Molt-4, and Raji cells). The growth of each cell line was inhibited by the cocultivation with bestatin at higher concentrations than employed for clinical use in Japan. [3H]TdR incorporation was also inhibited in MT-1 and MT-2 cells by treatment with bestatin. Degenerated cell-to-cell adhesion was observed among the treated cells. These findings suggest that the inhibitory effect on some leukemic cells, especially on MT-1 cells, results from the inhibition of DNA synthesis. PMID- 2223153 TI - Bestatin treatment of myelodysplastic syndromes (MDS) and the effects of bestatin on hematopoiesis in MDS. AB - A high remission rate (75%) was achieved in a preliminary study using bestatin in patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-t). One of 2 patients with RAEB-t and 3 of 6 patients with RAEB obtained complete response. Two patients with RAEB achieved good response, but one with refractory anemia failed. Clonogenic marrow cell culture studies in patients with myelodysplastic syndromes have demonstrated intrinsic hematopoietic stem cell abnormalities, in particular defective erythroid colony formation. After bestatin treatment, these abnormalities as well as hematologic findings were markedly improved. The results suggest that bestatin has an enhancing effect on burst promoting activity production of helper (CD4 positive) T lymphocytes and the effect on hematopoiesis of bestatin may be mediated by T lymphocytes. PMID- 2223154 TI - Adjuvant bestatin (Ubenimex) treatment following full-dose local irradiation for bladder carcinoma. AB - The clinical value of adjuvant bestatin (Ubenimex) immunotherapy has been examined in a group of patients with urinary bladder cancer. Patients with non metastatic transitional cell carcinoma of the bladder, scheduled for full-dose local irradiation therapy (64 Gy), were randomly allocated to adjuvant oral bestatin treatment (30 mg daily for at least 1 year), starting at completion of irradiation, or no bestatin. The trial included 194 evaluable patients with a follow-up period of 1.5-9.5 years. The overall survival of the two groups of patients did not differ statistically significantly (97 patients in each). Subgrouping of the patient material gave no evidence that the clinical efficacy of bestatin is related to sex, tumor category or malignancy grade. PMID- 2223155 TI - Effects of bestatin on the host immunity in patients treated for urogenital cancer. AB - To examine effects of bestatin on the host immunity of patients with urogenital cancer, 54 patients were randomized into 2 groups: bestatin treated and controls. In each group, the patients were divided into 2 subgroups: one which received basic treatment expected to greatly affect host immunity ('invasive treatment') while the other one received other types of basic treatment ('non-invasive treatment'). Peripheral lymphocyte, OKT 4/8 ratio and purified protein derivative (PPD) skin reaction were used as immunological markers. There were significant differences in the 'invasive' treatment group between bestatin treated patients and controls concerning lymphocyte counts and PPD skin reactions and in the 'non invasive' group concerning lymphocyte counts and OKT 4/8 ratios. These results suggest that bestatin may potentiate host immunity in patients with urogenital cancer. Further studies on larger materials are, however, needed before more definite conclusions can be drawn. PMID- 2223156 TI - Combination therapy with bestatin in inoperable lung cancer. A randomized trial. AB - A randomized trial of combination therapy with bestatin (30 mg daily, every day) was performed in 238 patients with inoperable primary lung cancer from August, 1981 through April, 1984. Of the 238 patients, 227 were evaluable: 113 treated by bestatin combination therapy and 114 controls. There was no statistically significant difference in response rate or survival between the 2 groups. In squamous cell cancer response was observed in 34.5% of the bestatin group and 17.9% of the control group. The analysis, including Cox's proportional hazard model, revealed that the survival tended to be longer in the bestatin group (median survival 40 weeks) than in the control group (median survival 24 weeks; p = 0.051). This suggests that addition of bestatin might be beneficial in squamous cell cancer of the lung but further, more rigidly controlled, clinical trials are necessary before more definitive conclusions can be drawn. PMID- 2223157 TI - Bestatin in resected lung cancer. A randomized clinical trial. AB - A randomized study with and without bestatin, a new biological response modifier, was conducted in order to evaluate its survival effect on resected lung cancer. A total of 153 patients (72 with squamous cell carcinoma, 66 with adenocarcinoma, and 15 with other types of cancer) were evaluated. Among the patients with squamous cell carcinoma, the bestatin-treated group had significantly prolonged survival compared to the control group. No significant difference between the two groups was seen in adenocarcinoma. PMID- 2223158 TI - [Origin of DNA replication of filamentous coliphages]. PMID- 2223159 TI - Phylogeny and molecular evolution in primates. AB - Statistical methods for estimating the branching order and the branching dates from DNA sequence data, taking into account of the rate variation among lineages, are reviewed. An application of the methods to data from primates suggests that chimpanzee is the closest relative of man, and further suggests that these two species diverged about 4-5 million years ago. PMID- 2223160 TI - Avidin column as a highly efficient and stable alternative for immobilization of ligands for affinity chromatography. AB - The avidin/biotin system was applied as a general mediator in the adsorption/desorption or immobilization of biologically active macromolecules to solid supports. In this context, model biotinylated proteins (lectins and antibodies) were attached to avidin-coupled Sepharose. As examples for affinity chromatography, peanut agglutinin and anti-transferrin antibody were used to isolate asialofetuin and transferrin, respectively. The capacity and product yields were significantly better than those achieved with conventional affinity chromatography on CNBr-activated Sepharose columns containing the same lectin or antibody. Moreover, the columns were characterized by improved stability properties exhibiting remarkably low levels of leakage. PMID- 2223161 TI - Antibody affinity measurements. AB - The use of antibodies in immunoaffinity separations represents one of the most specific methods for purifying substances of biological interest. Since the binding affinity of antibody greatly influences its behavior in such separations, it is often important to know the value of the antibody affinity expressed as an equilibrium constant K. The present review discusses the equations used in the quantitative analysis of antigen/antibody interactions and describes currently used experimental methods for measuring K values. Advantages and shortcomings of the solution phase and solid phase approaches used for measuring antibody affinity are discussed. PMID- 2223162 TI - New developments in affinity chromatography. AB - The design, synthesis and chromatographic operation of a new range of stable and selective immobilized dye affinity adsorbents for potential application in the purification of pharmaceutical proteins is described. Computer aided molecular design has been exploited to design novel dye ligands which show a predictable selectivity for the target protein and which, when coupled to stable perfluoropolymer supports, yield high capacity, low leakage adsorbents for affinity chromatography. It is anticipated that these new materials will withstand the rigorous conditions required for sanitization and cleaning in situ of industrial scale processes. PMID- 2223163 TI - Investigation of dye/protein interaction and its application to enzyme purification. AB - In this review the results of the interaction of the active dyes used in the USSR textile industry with microbial enzymes and blood serum proteins are discussed. The complexity of dye/protein interaction and the dependence of this interaction on different factors is demonstrated. Some practical aspects of the use of dye containing sorbents are presented and discussed. Their suitability for RNA ligase and DNA ligase, acetate kinase, alcohol dehydrogenase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase purification and blood serum protein fractionation is demonstrated. PMID- 2223164 TI - Diagnosis and treatment of impotence. AB - Among the common procedures used in the diagnosis of impotence, neither nocturnal penile tumescence testing nor inhome monitoring devices designed to measure tumescence or rigidity is regarded as reliable for evaluating impotence. Plethysmography as a nonspecific test of vascular competence is increasingly being supplanted by Doppler ultrasound as a safe and effective diagnostic modality. Arteriography, cavernosography, and cavernosometry are established techniques for evaluating penile vasculature. Intracavernosal injection of smooth muscle relaxing drugs, endocrine assays, and electrophysiological testing are widely used for the diagnosis of impotence. Excluding implanted devices, and intracavernosal injections. Aortoiliac reconstruction, endarterectomy, or arterial dilatations are regarded as safe and effective for the treatment of proximal occlusive lesions, and venous leakage surgery is regarded as investigational. Intracavernosal injections are widely employed in clinical environments and for self-injection at home. However, this currently represents the use of FDA-approved drugs for an unlabeled indication. The use of external vacuum devices has achieved widespread use and is regarded as being safe and effective for the treatment of impotence. PMID- 2223165 TI - Dependency, social factors, and the smoking cessation process: the doctors helping smokers study. AB - We analyzed data obtained from a representative sample of the smoking patients (n = 1,338) of 66 family physicians to determine predictors of attempts to stop smoking, desire to quit smoking, and successful smoking cessation. Compared to subjects who made no attempt to quit smoking, subjects who tried to quit smoking tended to be younger, had tried to quit smoking in the year prior to the study, waited longer before smoking their first cigarette of the day, had more desire to quit smoking, and had more social support for quitting. Education and cigarettes smoked per day were not independently related to the subject making a quit attempt. Desire to quit smoking was associated with an attempt to quit in the year prior to the study and social support for smoking cessation (support of spouse, second most important social contact, and physician). Desire to quit smoking was not independently related to age, education, or dependency on cigarettes (measured by the number of cigarettes smoked per day and the length of time a subject waited before smoking the first cigarette of the day). Compared to subjects who tried to quit and failed, subjects who succeeded were older, smoked fewer cigarettes per day, and waited longer to smoke their first cigarette of the day. Spouse support, support of the second most important social contact, and advice of a doctor to quit smoking were not independently related to whether or not a cessation attempt would be successful. These data suggest that successful smoking cessation requires two components: social support to make an attempt to quit and the ability to overcome dependency on cigarettes to make the attempt successful. PMID- 2223166 TI - Ethnicity and smoking: differences in white, black, Hispanic, and Asian medical patients who smoke. AB - To describe differences in the attitudes and behaviors of white, black, Hispanic, and Asian medical patients who smoke, we surveyed 2,835 patients of primary care physicians who participated in a controlled trial on smoking cessation. White smokers smoked more cigarettes per day, were more addicted to cigarettes, had more smoking-related symptoms and illnesses, and were more likely to relate smoking to their symptoms and illnesses. Black smokers found less pleasure in smoking, expressed the least concern about the health risks of smoking, but reported the greatest desire to quit and most confidence that they could quit. Hispanic and Asian smokers more often wanted to quit to keep their children from being exposed to smoking. We conclude that a single approach to helping patients quit smoking is less likely to be effective than one tailored to the ethnic differences among those patients. PMID- 2223167 TI - A smoking cessation incentive program for chemical employees: design and evaluation. AB - Worksite smoking cessation intervention programs have become increasingly popular, although program evaluations are often unavailable. In 1984, the Texas Operations of Dow Chemical USA offered a Smoking Cessation Incentive Program (SCIP) to its employees. SCIP was a highly publicized, upbeat program that had the active support of management and union. Altogether, 7,516 employees (95.4% of all employees) were surveyed about their smoking habits; 28.3% identified themselves as smokers. A total of 1,113 employees voluntarily enrolled in SCIP from March 1, 1984, through March 1, 1985. Smoking cessation methods included a buddy program, nicotine-containing chewing gum, American Lung Association self help material and group clinics, and incentive prizes. SCIP registrants, compared to employees identified as smokers in a pre-program survey who did not participate in SCIP, were significantly (P less than .01) more often females, whites, administrators, professionals, heavier smokers, and smokers who had tried to quit at least two times prior to SCIP. There were 326 (29.3%) SCIP participants who quit smoking for at least one month during SCIP. A total of 265 (23.8%) succeeded at quitting for at least six months and remained ex-smokers at the end of the program. Logistic regression analysis showed administrators had significantly higher six-month or more rates of quitting than did professionals, craftsmen, operators or clerical workers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223168 TI - Effectiveness of methods used to teach breast self-examination. AB - The efficacy of breast self-examination (BSE) is limited by the extent to which women can be taught to perform a frequent and proficient examination. We randomized 783 women from a health maintenance organization into group instruction, individual instruction, individual instruction with a reminder system, or minimal intervention designed to simulate an office encounter where BSE was encouraged but not taught. The percentage of lumps 1 cm and smaller detected in silicone breast models, the number of false-positive detections, the search technique, and the self-reported BSE frequency were measured before and four months after intervention. Multiple tests for comparisons of interventions showed that the interventions containing BSE instruction were comparable in increasing true- and false-positive detection of lumps and in improving search technique, but the minimal intervention resulted in lower scores for all three outcomes (P less than .0001). Women in all four intervention groups increased their BSE frequency over the four-month follow-up period, but the greatest improvement in frequency was reported among women receiving reminders. PMID- 2223170 TI - Health consciousness and health behavior: the application of a new health consciousness scale. AB - Self-consciousness has been an important trait in personality research. It seems logical to investigate whether health consciousness, involving a similar self focusing, might operate in a parallel manner. To this end, I developed the Health Consciousness Scale (HCS), primarily by modifying items of the Self-Consciousness Scale, and also tested it for reliability and validity. My study found the HCS to contain four first-order factors: (1) Health Self-Consciousness, (2) Health Alertness, (3) Health Self-Monitoring, and (4) Health Involvement. I found these four first-order factors, along with the overall HCS second-order factor, to relate to a number of self-reported, health-associated behavioral variables. The study also included comparisons with the Health Locus-of-Control Scale and other measures. PMID- 2223169 TI - Children's frequency of consumption of foods high in fat and sodium. AB - We administered a food frequency instrument to third-fifth grade students (n = 943) in four Texas schools. Comparison of foods reported on the food frequency questionnaire and on 24-hour dietary recalls (n = 7) produced a percent agreement of 83.3. The most frequent 25 foods accounted for 64.0% of food choices across all meals, 93.5% of breakfast choices, 76.4% of lunch choices, 70.5% of supper choices, and 76.0% of snack choices. Breads, milk, hamburger or steak, soda pop, tomato sauce or tomatoes, and cheese were the most frequently consumed foods. Fruits and juices accounted for 6.1% of total selections for boys and 6.6% for girls, while vegetables accounted for 15.7% of total selections for boys and 16.2% for girls. Fruit was more likely to be consumed for snacks than for meals, and vegetables were consumed in about the same frequency at lunch and supper and for snacks. We analyzed the total fat, saturated fat, and sodium content of the most frequently consumed foods. Seventeen of the top 25 foods for the total day and 13-16 for each meal or snack exceeded by at least 50% the recommended levels for fat, saturated fat, or sodium. The pattern of consumption was one of frequent consumption of a relatively small number of foods, many of which are high in fat or sodium. PMID- 2223171 TI - Bowen's disease (squamous cell carcinoma in situ) as a skin marker for internal malignancy: a case-control study. AB - Bowen's disease has been viewed as a skin marker for internal malignancy by dermatologists for decades. If substantiated, it certainly would help in early detection of an occult malignancy. We conducted a matched case-control study to evaluate the significance of this link. Ninety patients with Bowen's disease diagnosed between 1972 and 1986 were selected for study. These patients were matched by age, sex, race, and date of biopsy for diagnosis (or treatment) to 90 other patients chosen as controls. Six patients in the Bowen's disease group and three patients in the control group had internal malignancy during the period after the date of biopsy or treatment (P greater than 0.4). The present study cannot substantiate the claim that Bowen's disease is a skin marker for internal malignancy. PMID- 2223172 TI - High-resolution computed tomography of the pulmonary parenchyma. PMID- 2223173 TI - Computed tomographic scanning of the thorax in workers at risk of or with silicosis. PMID- 2223174 TI - Computed tomography of benign pleural and pulmonary parenchymal abnormalities related to asbestos exposure. PMID- 2223175 TI - Acute radiation-induced pulmonary injury: computed tomography evaluation. PMID- 2223176 TI - High-resolution computed tomography in pulmonary sarcoidosis. PMID- 2223178 TI - [Perinatal brain injuries and subsequent epilepsy: a study on intraventricular hemorrhage in preterm infants and hypoxic-ischemic encephalopathy in full-term infants]. AB - The clinical course of symptomatic epilepsy caused by intraventricular hemorrhage (IVH) in 7 preterm infants and hypoxic-ischemic encephalopathy (HIE) in 9 full term infants were followed up for more than 2 years and 6 months. West syndrome was the first manifestation of epilepsy in 10 cases (IVH: 4, HIE: 6), and all 16 patients had severe neuropsychiatric deficits. Comparing with children without epilepsy, IVH grades III and IV, mechanical ventilation for more than 6 days and neonatal convulsions in the patients with IVH, and mechanical ventilation and neonatal convulsions in the patients with HIE, were significantly related to the risk of subsequent epilepsy. These findings suggest that the degree of brain injuries may be predictive of the development of epilepsy during infancy and early childhood in the patients with IVH or HIE. PMID- 2223177 TI - Computed tomographic assessment of bronchiectasis. PMID- 2223179 TI - [Meningoencephalitis in Kawasaki disease]. AB - Kawasaki disease (KD) is a syndrome characterized by various degrees of vasculitis in small-and medium-sized arteries. We discussed the characteristic manifestations and prognosis of 5 KD patients (male 3, female 2) with meningoencephalitis in the acute stage. The incidence was 3.7% (5 of 138 patients) in our institute. The age of onset was between 3 months and 15 months. The clinical manifestations included disturbance of consciousness and seizures; disturbance of consciousness developed in all patients in the early acute stage. The duration was between 2 and 11 days; seizures developed as status convulsions in two. Electroencephalograms (EEG) demonstrated certain abnormalities in 2 of 4 patients studied. Computed-tomographic scanning (CT scan) revealed fluid collection in the frontal extracerebral space, and monocyte-predominant pleocytosis was observed in the cerebrospinal fluid (CSF) in all 5 patients studied. The age of onset in the 5 KD patients was significantly earlier than that in non-complicated cases (n = 138, P less than 0.01). Blood hemoglobin (P less than 0.05) and hematocrit (P less than 0.05), serum total protein (P less than 0.01), and serum albumin levels (P less than 0.01) were also significantly lower. Moreover the period until CRP values turned negative was significantly longer (P less than 0.05) and erythrocyte sedimentation rate was significantly lower (P less than 0.01) in these 5 patients. It was considered that meningoencephalitis in KD may develop in cases having more severe and prolonged inflammatory changes; the clinical findings revealed a serious form of KD. We suggest that this might because by vasculitis of small arteries, arterioles, capillaries, and venules, which consists of infiltration of lymphocytes and large mononuclear cells, and edema. There was no neurological sequela in 4 of the 5 patients. However, one patient was found to have hearing difficulty 3 years after the onset. Therefore, the prognosis of meningoencephalitis in KD was considered to be generally favorable. PMID- 2223180 TI - [Mental deterioration in childhood epilepsy. I. Neuropsychological and electroencephalographic studies]. AB - To clarify the pathogenesis of mental deterioration in epilepsy, neuropsychological and electroencephalographic studies were performed. Thirty seven children were classified into two groups: group I consisted of 24 children with mental deterioration during the clinical course of their epilepsy, and group II consisted of 13 children without mental deterioration. Mental deterioration was assessed on the basis of the intelligence test scores during follow-up studies. The mean intelligence quotient of 24 children in group I decreased from 91.8 +/- 11.5 to 64.3 +/- 15.4 during a mean period of 4.4 years. Significant differences were found between the two groups in the levels of both representation (association function) and automation (auditory closure, visual recognition and visual-motor function). There were also significant differences between the two groups in the continuation of epileptic discharges on EEG, in the persistence of epileptic attacks at the final visit, and in the numbers of antiepileptic drugs at the neuropsychological examination. The degree of mental deterioration was correlated with the defect in the association function and, eleven children in group I showed mental deterioration even after their attacks had been suppressed. PMID- 2223181 TI - [Paradoxical alpha waves seen in the course of subacute sclerosing panencephalitis]. AB - Serial EEG findings of two cases with subacute sclerosing panencephalitis were compared with concurrent clinical status and CT findings. Case 1, a 16-year-old boy, showed transient abnormal diffuse alpha waves during sleep record. That had been seen for six months after the disappearance of periodic synchronous discharges. Clinically this abnormal EEG finding was observed at the transitional phase from stage II to III, when CT showed severe brain atrophy. Case 2, an 11 year-old boy, showed similar abnormal alpha waves for three months in the same phase as case 1. There have been many reports regarding the EEG findings of SSPE. However, these abnormal EEG findings were not reported. These abnormal alpha waves during sleep are considered to develop at the transitional phase from stage II to III, when pathologically SSPE goes from inflammation to destruction. PMID- 2223182 TI - [Experimental study on pathogenesis of neonatal hypoxic-ischemic encephalopathy. I. Histopathological study]. AB - This experiment was undertaken to study the effect of hypoxic and/or ischemic condition on developing brain and also to investigate the pathogenesis of hypoxic ischemic encephalopathy. A unilateral common carotid artery of 7-day-old Sprague Dawlay rats was ligated and cut under ether inhalation. Three hours after the operation, these rats were exposed to hypoxia (8% oxygen and 92% nitrogen mixture) for two hours. Three days after manipulation, neuronal necrosis on the ligated hemisphere were recognized in 50% in the cortex, 66.7% in the hippocampus, 66.7% in the corpus striatum and 33.3% in the thalamus. Various sizes and degrees of necrotic regions were found in the cerebral cortex. In some cases, cuffs of radially arranged viable neurons alternating with stripes of full depth necrosis of the cortex were noticed. In the hippocampus, neuronal necrosis was found segmentally at the pyramidal cell layer. In the corpus striatum and the thalamus, the damage consisted of small focal or multifocal neuronal necrosis. After four and eight weeks of the manipulation, a large porencephalic cavity in the cerebral cortex of the ligated side was noticed as the severest manifestation in 16% of the cases. In some cases, multiple lobulation similar to poly microgyrus was noticed. Various sizes of gliosis were also numerous in the cerebral cortex, hippocampus, corpus striatum and thalamus of the ligated side hemisphere. Calcified lesions were also occasional in the basal ganglia. PMID- 2223183 TI - [Experimental study on pathogenesis of neonatal hypoxic-ischemic encephalopathy. II. Energy metabolism in the brain]. AB - In a preceding paper, we showed that the exposure to hypoxia after unilateral carotid artery ligation of sucking rat on 7 days of age caused various pathological changes in the ipsilateral forebrain, which had close similarity to human perinatal hypoxic-ischemic encephalopathy. To evaluate the energy metabolism in various regions of the brain during hypoxia after unilateral carotid artery ligation, tissue pH was monitored in the cortex by direct insertion of an electrode. The contents of the lactate, pyruvate, ADP and ATP were also measured during hypoxia. The tissue pH in the cortex of ligated side declined rapidly after initiation of hypoxia as compared to non-ligated side. The contents of pyruvate and ADP showed no particular changes through various regions. Only in the cortex and hippocampus of ligated side, ATP was decreased, and elevation of lactate was more salient than in non-ligated side. In the striatum and thalamus, only elevation of lactate was indicated. However, the levels of lactate, pyruvate, ADP and ATP disclosed no significant difference between the ligated side and non-ligated side, although neuropathological changes were observed only in their ligated side. These results suggest that pathogenesis of the cerebral damage caused by hypoxic-ischemic condition may be different between the cerebral cortex and subcortical structures. PMID- 2223184 TI - [Repetitive rhythmic spikes in epileptic children]. AB - Repetitive rhythmic spikes (RRSs') sometimes appear periodically for 0.2-2.0 seconds at localized in epileptic children. We selected 11 patients (male 6, female 5) with RRSs for this study. Ages were 3-15 years (average 10.7 years). We counted the number of spikes which were recorded on the scalp EEG. The duration of RRSs and the differences of amplitude between large and small spikes on monopolar montages were examined. We also studied the appearance of spikes under different recording conditions; waking and sleep stages, photic stimulation and hyperventilation. Furthermore, we made two dimensional joint-dot plotting for the interval between repetitive spikes. RRSs were classified into two groups. In the first group, joint-dots of RRSs were locally observed between 0.2-0.8 sec. In the second, they were disseminated between 0.2-2.0 sec. In two groups, spikes were mainly observed in the sleep EEG (stage 1). The average number of spikes in the first group was 18.7/min, and that in the second was 25.7/min. The average difference of the amplitude between large and small spikes was 103 microV in the first group, and 88 microV in the second group. The average duration of spikes was 54.2 msec in the first group and 62.4 msec in the second group. From these results, it was assumed that some of spikes in the first group occurred in the surface of the cortex and that some of spikes in the second group were projected from the deep region in the cortex. PMID- 2223185 TI - [Electrophysiological studies on hydranencephaly]. AB - Electrophysiological studies were performed on two children with hydranencephaly that was diagnosed by CT and/or magnetic resonance imaging (MRI). Case 1 was a 4 months-old boy who had no rostral tissue above the midbrain. Case 2 was a 5-years old boy in whom CT showed the presence of the thalamus. Short latency somatosensory evoked potentials (SSEP) in both cases exhibited the absence of cortical activity (N1 and P4) with the preservation of waves of brainstem origin. However, in case 1, the wave component N0 was not observed, while N0 was seen in case 2. Thus, the N0 was component of SSEP on median nerve stimulation in children, which corresponds to N16 in adults, may originate in the thalamus. PMID- 2223186 TI - [Effect of high-dose methotrexate on cerebral metabolic rate of glucose in rats and children with acute lymphoblastic leukemia]. AB - For assessment of high-dose methotrexate (HD-MTX) neurotoxicity, regional cerebral metabolic rates of glucose (rCMRGlu) in rats and children with acute lymphoblastic leukemia were measured. rCMRGlu in rats receiving HD-MTX (300 or 600 mg/kg) was measured using 14C-deoxyglucose and autoradiographic technique. CMRGlu of the whole brain after HD-MTX was reduced by 31% on the average (p less than 0.01). CMRGlu of cerebral cortex was reduced more than that of white matter. Eight children with ALL (mean age 9.6 years) were studied using 18F fluorodeoxyglucose and positron emission tomography before and after HD-MTX (200 mg/kg or 2,000 mg/M2) therapy. Although no patients clinically showed any neurological abnormalities during HD-MTX therapy, CMRGlu of the whole brain after HD-MTX was reduced by 21% on the average (p less than 0.05). Reduction rates of rCMRGlu after HD-MTX therapy were correlated with both total doses of intrathecal MTX (r = 0.717, p less than 0.05) and total doses of systemic HD-MTX (r = 0.784, p less than 0.05). The reduction rate of CMRGlu of cerebral cortex, particularly frontal and occipital cortex, was greater than either that of basal ganglia or white matter. It is suggested that measurement of rCMRGlu after HD-MTX is useful for detecting accumulated neurotoxicity of MTX. PMID- 2223187 TI - [Vestibular function in severely retarded children in relation to their motor disabilities]. AB - We examined vestibular functions of thirty-one severely retarded children with caloric test and rotation nystagmus test, in combination with auditory brainstem response (ABR) recordings and measurement of brainstem width on cranial CT scans. The laterality of vestibular response was over 20% in most of the bedridden cases and was under 20% who could move. Abnormal findings in ABR had no relationship with the degree of motor disabilities, but decreased width of brainstem on CT scan showed some relationship with the degree of motor disabilities. We conclude that vestibular function tests are useful to predict future motor development in severely retarded children. PMID- 2223189 TI - [Visual evoked potential abnormalities in a girl with brain stem encephalitis (Bickerstaff)]. AB - A 16-month-old girl was admitted because of bilateral ophthalmoplegia, left blepharoptosis, and disturbance of consciousness. Her symptoms resolved spontaneously within a week after admission, but mild left abducens palsy remained. The cranial computed tomography showed a mild non-specific brain atrophy. The auditory brain stem response was normal. Visual evoked potentials (VEPs) to flash stimuli were repeated serially after the onset. No significative patterns of VEP were evoked during the acute stage. However, three months after the onset, an asymmetrical pattern, namely left-sided abnormalities (not identified P 100 wave, etc.), was observed. The asymmetrical pattern of VEP diminished six months after. And a bilaterally normal VEP pattern was found twelve months after. PMID- 2223188 TI - [A case of herpes simplex encephalitis with cerebral white matter lesion after acyclovir administration]. AB - Herpes simplex virus (HSV) is regarded as an agent that selectively affects temporal and frontal lobes with necrosis and hemorrhage, and no case of herpes simplex encephalitis (HSE) with white matter lesion in a diffuse fashion has previously been reported. A 2-year-old boy developed high fever, right hemi convulsions and lethargy. Computed tomography (CT) showed wedge-shaped areas of high density in the left frontal region, whereas, cerebral angiography disclosed no vascular abnormality. T1-weighted magnetic resonance imaging (MRI) demonstrated cortical changes which were similar to those illustrated by CT. However, T2-weighted images depicted further spread high intensities of the lesion. The patient's symptoms spontaneously disappeared before an antiviral drug, acyclovir, was administered. After the significant increase of HSV antibody titers in serum and cerebro-spinal fluid (CSF) established a definite diagnosis, acyclovir was intravenously given at a daily dosage of 30 mg/kg for a period of 6 days in order to prevent the recurrence of HSE. Two months later, T2-weighted MRI visualized a diffuse lesion of increased signal intensities involving the white matter of both hemispheres, while both CSF protein and myelin basic protein were significantly elevated. Despite of these changes of the white matter, our patient developed a few symptoms such as mild speech disturbance, slight weakness of the right upper limb and sialorrhea. Although the mechanism of these changes in the white matter remains obscure, it is postulated that a direct invasion of HSV to the white matter, an immunological disorder following HSV infection and a side effect of acyclovir could have triggered a reversible process of demyelination of the cerebral white matter. PMID- 2223191 TI - [A case of hemorrhagic shock and encephalopathy]. PMID- 2223190 TI - [Chronological change of EEG findings in a case of pyridoxine dependency seizures]. AB - A patient of pyridoxine dependent seizures was reported. He was born at 34 weeks' gestation and weighted 2,760 g. Apgar scores were 6 and 9 at 1 and 5 minutes, respectively. He showed the first seizure 2 hours after his birth. Phenobarbital, phenytoin, sodium valproate, diazepam and clonazepam were not effective. Pyridoxal phosphate (50 mg) was given intravenously, resulting in suppression of convulsions. However, muscle tonus was severely depressed. In EEG, a discontinuous pattern was found in quiet and indeterminate sleep on the 2nd day of life. At 5th week multifocal spikes were found, and the discontinuous pattern persisted. Ictal discharges at 13th week showed generalized, continuous, irregular and high voltage slow waves with multifocal spikes. At 27th week of life, high voltage slow waves disappeared and multifocal spike discharges decreased. At 2 years and 10 months of age, the patient was suffering from athetotic cerebral palsy and severe mental retardation. Pyridoxal phosphate at the doses of 35-40 mg/kg/day had been administered. Irritability sometimes occurred and additional 50 mg of pyridoxal phosphate controlled this irritability effectively. PMID- 2223192 TI - [A single case of autosomal recessive muscular dystrophy of childhood- histological and immunocytochemical studies on biopsied muscle]. PMID- 2223193 TI - [Inequality of bioavailability in commercial tablets of valproic acid]. PMID- 2223194 TI - Behavioural change and the stress-coping paradigm: some comments on modelling the European code on avoiding cancer. AB - The Europe Against Cancer Campaign's ten-point code is considered. The difficulties involved in conceptualizing an extremely diverse set of behaviours are highlighted. A framework for modelling the code, based upon the stress-coping paradigm, is presented. PMID- 2223195 TI - Leukaemia incidence, social class and estuaries: an ecological analysis. AB - Leukaemia incidence data for 1984-1986 for 22 counties of England and Wales have been collected by a specialist registry. The present study is an ecological analysis in which incidence in electoral wards has been tested for association with two predefined ward characteristics: socio-economic status and proximity to estuaries. Small but statistically significant associations have been observed with relative risks in the range 1.05-1.50. Adjustments have been made in the analysis for variation in the underlying regional incidence and also for statistical artefacts consequent upon the rarity of the condition. The results for socio-economic status confirm those of other recent studies, with increased incidence linked to higher status. The results for estuaries are new although derived from a prior hypothesis. PMID- 2223196 TI - A study of selected death certificates from three Dublin teaching hospitals. AB - One hundred death certificates were compared over two time periods with the corresponding autopsy reports on the cases to ascertain if the causes of death from the two sources were similar. There was poor concordance between the two and it seems likely that reasons for requesting an autopsy did not extend to using the information to complete the death certificates. There were 55 errors on 45 certificates, and 19 certificates were so inaccurate as to warrant a change in the underlying cause of death. In only 10 cases was the certificate signed before the autopsy report was available; however, should clinicians have wished to add autopsy findings to the certificate later, there is no facility on the Irish death certificate to do so. A revision of the format of the certificate is recommended. An examination of death certificates from varied medical sources would be welcome to see if the serious errors identified in this study are more widespread. PMID- 2223197 TI - Measles/mumps/rubella vaccine (MMR): an audit of Leeds health professionals' knowledge of contraindications and intention to vaccinate assessed by postal questionnaire. AB - An audit of Leeds health professionals' knowledge of valid contraindications to measles/mumps/rubella (MMR) vaccine was undertaken by postal questionnaire, three months after its introduction. The health professional groups were health visitors, clinical medical officers, general practice trainers and general practice vocational trainees. The results indicate that some health professionals would give MMR vaccine to children when it was contraindicated (e.g. to a child receiving chemotherapy or radiotherapy). However, a much greater problem was the number of health professionals stating that they would not vaccinate children with MMR vaccine in clinical situations where there were no valid contraindications to its use. Some health professionals were also applying contraindications to the use of pertussis vaccine to the use of MMR vaccine. The information contained in the Joint Committee on Vaccination and Immunisation handbook Immunisation against infectious disease on contraindications to MMR vaccine use is also reviewed. It is important that false contraindications are not used by health professionals to wrongly deny children the protection provided by MMR vaccine. PMID- 2223198 TI - Possible factors affecting response to postal questionnaires: findings from a study of general practitioner services. AB - Poor response rates affect the validity of results from postal questionnaires. The effect of three controllable factors upon response rates was examined in a recent study of patients' experiences and views of general practitioner services. The factors studied were the institution from which questionnaires were dispatched, the length of the questionnaire and the inclusion of a potentially sensitive question about ethnic origin. Questionnaires sent out by local Family Practitioner Committees were more likely to be returned than those sent out by a London-based independent research unit, but there were no differences in the nature of replies obtained. Neither the length of the questionnaire nor the inclusion of the potentially sensitive question affected response rates. The results of the study indicate that Family Practitioner Committees wishing to carry out postal surveys of users of general practitioner services can obtain satisfactory response rates. PMID- 2223199 TI - Communicable disease report October to December 1989. From the PHLS Communicable Disease Surveillance Centre. PMID- 2223200 TI - Confidence limits for Nottingham Health Profile scores: some empirical results. PMID- 2223201 TI - A lesson from Europe? PMID- 2223202 TI - Blood cholesterol, social class and height. PMID- 2223203 TI - Meningitis Resource Pack (the Meningitis Trust 1989) PMID- 2223204 TI - Quality assurance of medical care. PMID- 2223205 TI - [The use of skeletal muscles for assisting the failing myocardium]. PMID- 2223206 TI - [Surgical treatment of patients with tetralogy of Fallot in combination with a double aortic arch]. AB - A late congenital anomaly--double arch of the aorta (DAA)--was combined with Fallot's tetrad (FT) in 4 patients whose ages ranged from 21 months to 11 years. The diagnosis of DAA and FT was established before the operation in 3 patients, in one patient DAA was discovered during the operation. In three children DAA was manifested clinically by dysphagia and stridor. A palliative operation (FT) was carried out through a left posterolateral approach along the third intercostal space. One-stage separation of the vascular ring by cutting the smaller left arch of the aorta at its junction with the descending aorta and formation of anastomosis between this arch and the left pulmonary artery by the end to side method were conducted. In deficient length of the cut arch of the aorta the left subclavian artery was divided; in equal diameter of both arches the lumen of the arch was reduced to 0.5 cm with stitches before formation of the anastomosis so as to prevent hyperfunction of the shunt. In the case in which DAA was not recognized before the operation, an attempt to dilate the hypoplastic segment of the left arch led to rupture of the thinned wall and the patient died from hemorrhage. The advantages of one- and two-stage radical correction of both developmental anomalies (DAA and FT) are still debatable. PMID- 2223207 TI - [The surgical treatment of an aortic aneurysm following a prior correction of its coarctation]. AB - In a group of 381 patients who were operated on for coarctation of the aorta 34 (8.9%) were found to have an aneurysm of the aorta in the zone of the correction in the late-term postoperative period. The frequency of aneurysm formation was greater in patients with flap plastics. Fifteen patients underwent a second operation for aneurysm of the aorta, 2 (13.3%) of them died. In the group of patients who were not operated on 6 (31.6%) died. PMID- 2223208 TI - [The topographic-anatomical rationale for using the right gastro-epiploic artery for direct revascularization of the myocardium]. AB - The topographic anatomy of the right gastroepiploic artery was studied on anatomical material and a model of an operation was elaborated for direct revascularization of the myocardium with the use of the right gastroepiploic artery as a pedicled shunt. The study showed that the anatomical characteristics of the artery (length, diameter) allow it to be used as an autoarterial shunt to the coronary arteries. The authors discuss two methods for installing the vascular graft by means of which shunting of the coronary arteries of both the anterior and the posterior myocardial wall can be accomplished with a graft of the right gastroepiploic artery. PMID- 2223209 TI - [Experience in hemoconcentration by ultrafiltration in operations using artificial circulation at the All-Union Scientific Center of Surgery of the USSR Academy of Medical Sciences]. AB - The article deals with the results of using ultrafiltration hemoconcentration in 649 operations conducted on the open heart with extracorporeal circulation at the All-Union Scientific Center of Surgery, USSR AMS during 1983-1989. The method allows control of hemodilution and colloid-osmotic pressure of plasma during the indicated interventions, lessens the loss of blood, and reduces the expenditure of donor blood. PMID- 2223210 TI - [Methods of solving the problem of the surgical treatment of post thrombophlebitic disease of the lower extremities]. PMID- 2223211 TI - [Tactics and indications in the surgical treatment of patients with combined extra- and intracranial lesions of the carotid arteries]. AB - The article deals with the results of surgical treatment of 159 patients with concomitant extra-intracranial and bilateral lesions of the carotid arteries; 163 operations were conducted for the formation of an extra-intracranial microanastomosis (EICMA) among which 75 operations comprised reconstruction of extracranial segments with creation of EICMA. In 66 cases EICMA was performed in contralateral stenosis of the internal carotid artery (in 22 with subsequent carotid endarterectomy), in 14 cases as the first stage before reconstruction of the iliofemoral segment, and in 8 cases in occlusion of the middle cerebral artery or in tortuous carotid arteries. Complex examination was conducted, including ultrasonic dopplerography, transcranial dopplerography, study of cerebral blood flow according to Xe-133 clearance, and angiography. The late-term results of surgery were studied in follow-up periods of 6 months to 5 years. It was found that to appraise the indications for surgical treatment it is necessary to take into account the data obtained in studying the regional cerebral blood flow. Surgical treatment is indicated in occlusion of the internal carotid artery (with preliminary reconstruction of extracranial segments when they are involved) in patients with unstable type of cerebral hemodynamics, which is most characteristic in patients with transitory ischemic episodes, dyscirculatory encephalopathy, small apoplexy and predominantly with mild sequelae of ischemic apoplexy. PMID- 2223212 TI - [Disorders in the sequence of regional metastasis and long-term results of the surgical treatment of complicated lung cancer]. AB - To ascertain the frequency of disturbance of the stage character of regional metastasis in lung carcinoma complicated by disintegration or obstructive pneumonitis, and its influence on certain results of surgical treatment, the authors analysed the data on 175 patients who underwent lung resection. The stage character of regional lymphogenous metastasis was found to be disturbed in 61 (34.8%) patients, in 52 (85.2%) of them the main disease was complicated by obstructive pneumonitis. Five-year survival in the group of patients without disturbance of the stage character of metastasis was 28 +/- 4.8%, which was significantly greater than that in the group of patients with a disturbed stage character (15.5 +/- 5.2%). PMID- 2223213 TI - [Lung cancer in women in Moscow (epidemiology, etiology and surgical treatment)]. AB - In the studied period (1973-1987) the lung carcinoma morbidity rate among females of Moscow, in general intensive indices (per 100,000 females), showed a tendency to reduce (18.4 in 1973 and 15.1 in 1987). A reverse tendency is mostly encountered in other countries. More than half of patients with lung carcinoma were over 70 years of age. The ratio of males with lung carcinoma to that of females grew from 3.0:1.0 in 1973-1977 to 3.6:1.0 in 1983-1987. In the period from 1979 to 1988, 380 females suffering from carcinoma of the lung were hospitalized to the thoracic department of the clinic. Operations were performed on 215 of them, 174 of the operations were radical. The ratio of operated on males to females was 7.4:1.0. The frequency of central carcinoma among females was 28.8%, which was half that among males (56%). The number of operations according to volume was as follows: pulmonectomy 37, lob- and bilobectomy 119, wedge resection 18. More than half of the female patients had the glandular form of lung carcinoma and its incidence was 3-5 times that among males who were operated on (10-15%). According to the authors, the principal etiological factors are smoking, a history of another malignant tumor, and the exogenous effect of the consequences of urbanization. PMID- 2223214 TI - [The role of developmental disorders of the respiratory, digestive and vascular systems in pathology of the lungs in children]. AB - The results of diagnosis and treatment of bronchopulmonary pathology in 680 children were analysed. It was found that besides developmental anomalies of the lungs and trachea, those of the esophagus, mediastinal organs, diaphragm, and the aorta and its vessels play an important role in the pathogenesis of pulmonary diseases in infants and young children. Traditional and special methods of examination must be used in the diagnosis of these developmental anomalies. Timely correction of the developmental anomalies makes it possible to arrest the bronchopulmonary complications which are associated with them. PMID- 2223215 TI - [The importance of the compensatory powers of the lungs in determining the indications for surgical treatment of hypoplasia of the lungs]. AB - The author studied the compensatory possibilities of pulmonary respiration, gas exchange and hemodynamics of pulmonary circulation to determine the indications for operative treatment of simple hypoplasia of the lungs. The work is based on the results of examination of 58 patients. Forty-five patients underwent an operation. It was established that simple hypoplasia of the lungs is characterized by mild ventilation disorders and deep disorders of gas exchange leading to manifest and latent hypoxia in 94.6% of cases. Deficiently developed pulmonary-arterial channel, the presence of morphological foundations of pathological blood shunting (up to 24-32% of minute pulmonary circulation volume) were the causes of disturbed hemodynamics of pulmonary circulation and the development of pulmonary hypertension in 30.6% of cases. The indications and contraindications for surgical correction of simple hypoplasia of the lungs are discussed on the basis of study of the functional condition of ventilation, gas exchange, and hemodynamics of pulmonary circulation. PMID- 2223216 TI - [Therapeutic endoscopy in hemorrhages from varicose veins of the esophagus in patients with portal hypertension]. AB - The article discusses 6-year experience in the treatment and prevention of esophageal hemorrhage by endoscopic sclerotherapy using 96% and 70% ethanol as the sclerosant. There were 99 patients under observation whose ages ranged from 27 to 70 years, 74 were admitted to the clinic with profuse hemorrhage. Sclerotherapy arrested the bleeding in 65 (90%) patients. Seven patients died from persisting bleeding, 5 from increasing hepatic insufficiency, and one patient from perforation of the esophagus and purulent mediastinitis. After discharge from the clinic 54 patients were kept under observation for periods of 6 to 20 months; 16 episodes of bleeding occurred in 13 of them. Repeated sclerotherapy proved effective in 10 patients, 3 patients died from continuing bleeding and hepatic insufficiency. PMID- 2223217 TI - [A case of successful conservative treatment of acute purulent mediastinitis following heart surgery in conditions of artificial circulation]. PMID- 2223218 TI - [Angina pectoris developing 9 years after a heart wound not accompanied by injuries of the coronary arteries]. PMID- 2223219 TI - [The use of the deep femoral artery for restoring the blood circulation in the leg in the case of a gunshot wound]. PMID- 2223220 TI - [Bullous disease complicated by bilateral spontaneous pneumothorax in pregnancy]. PMID- 2223221 TI - [A neurofibroma of the esophagus]. PMID- 2223222 TI - [A congenital esophagotracheal fistula in an adult]. PMID- 2223223 TI - [Repeat surgery occasioned by the incompetence of the primary tissue in biological prostheses]. AB - The authors analyse the causes of repeated operations on 42 among a group of 157 patients with implanted biological cardiac valve prostheses and a postoperative follow-up period of 3.5 to 13 years. The main cause of dysfunction of biological prostheses is calcification which develops mostly in xenopericardial valves irrespective of their localization. Detachment of the cusps from the frame and their destruction is characteristic of allogeneic prostheses and those formed from the dura mater. Dysfunction of bioprostheses in the tricuspid position develops much later. PMID- 2223224 TI - [Cardiomyoplasty]. AB - The article analyses the current state of the problem of cardiomyoplasty as a new method for the treatment of patients with myocardial cardiac insufficiency. The authors show the experimental and clinical material on the possibility and efficacy of using skeletal muscles for improving myocardial contractility and raising the cardiac index. Experience gained in our country (6 operations) in cardiomyoplasty in patients with severe form of ischemic heart disease is discussed. The authors used an original Soviet produced cardiosynchronized electroneurostimulator "Stiminak" for stimulation of the muscles. Analysis of personal experimental material allows new ways for the development of the problem to be planned. PMID- 2223225 TI - [The use of skeletal muscles for assisting the failing heart]. PMID- 2223226 TI - [Diagnosis and surgical treatment of traumatic damage to the sinus of Valsalva following penetrating wounds of the heart]. AB - The authors had three patients with traumatic damage of the sinus of Valsalva, caused by penetrating injury of the thorax inflicted with a knife. The patients were brought to the clinic in a grave condition with decompensation of systemic and pulmonary circulation. The anomaly called for emergency surgical correction under conditions of extracorporeal circulation. The diagnosis was based on the complaints, medical history, clinical picture, the results of functional methods of examination including echocardiography and catheterization with angiocardiography. The operations consisted in total correction of the heart anomaly. The immediate and late-term results were good. PMID- 2223227 TI - [A new method of surgical treatment of vasculogenic impotence]. AB - The authors describe a method of surgical management of vasculogenic impotence consisting in the formation of an anastomosis of an autovenous shunt with the dorsal artery of the penis. To prevent revascularization of the cavernous bodies of the penis with the restoration of erection, the dorsal artery of the penis is divided transversely at the root of the penis, the distal end of the autovenous shunt is given the shape of a trapezium with the upper side sutured, after which the autovenous shunt is anastomosed end to end with both the distal and proximal segments of the dorsal artery of the penis at the lateral sides of the trapezium where the angles were not sutured. The method allows incompetence and thrombosis of the vascular anastomosis to be prevented, raises the efficacy of revascularization of the cavernous bodies of the penis by creating favourable hemodynamic conditions through separation of the blood flow into the distal and proximal segments of the dorsal artery of the penis, which provides retrograde supply of blood into the deep artery of the penis sufficient for adequate revascularization of the cavernous bodies. PMID- 2223228 TI - [Criteria for the selection of patients with a single heart ventricle for anatomical correction]. AB - The work deals with study of the functional condition of the myocardium in 34 patients with a solitary ventricle of the heart (SVH). The regional function of the myocardium was disturbed in all patients; the degree of the disturbance was determined by the anatomical variant of the SVH and was characterized by different distribution of the hypofunctioning segments in the ventricular myocardium. In view of that, to solve the problem of the possibility of accomplishing anatomical correction, the regional function in the zones of the future (after septation) ventricles must be evaluated. Radical correction may be performed with the least degree of risk in patients in whom the ejection fraction in each of the new ventricles will be greater than or equal to 55%. In the group of 17 patients only 5 conformed to this criterion. PMID- 2223229 TI - [Surgical aid in chest traumas]. AB - The article analyses the results of surgical treatment of 360 patients with traumatic damages of the thoracic organs in the Crimean Region from 1981 to 1989. The results proved to be best in patients who underwent operation in the Crimean Regional Pulmono-Surgical Center (RPSC). The clinical outcome was positive in 89.8% of patients. The results of treatment were somewhat poorer in patients who were operated on by thoracic surgeons at surgical departments and then transferred to the PRSC. No complications occurred in the postoperative period in 79.9% of cases. The results were poorest in patients who were operated on by general surgeons and transferred subsequently to the RPSC. Postoperative complications developed in 38.6% of cases. All complications in patients who underwent operation at general surgical departments were characteristically connected with inadequate evacuation of the exudate and air and inadequate cleansing of the bronchial tree. In view of this, organization of emergency aid in regional thoracic departments is the optimal variant. General surgical departments must be equipped with the appropriate apparatus. PMID- 2223230 TI - [Surgical tactics in bilateral resections of the lungs]. AB - The article generalizes experience in 118 bilateral resections of the lungs carried out within 4 years at the Chelyabinsk Regional Antituberculosis Hospital, among which 63% (74) were one-stage bilateral operations. A clinical effect was produced in 97.5% of patients. Postoperative mortality was 1.7%. The authors prefer one-stage bilateral resections and resort to stage-by-stage operations only in cases with severe concomitant diseases, marked respiratory insufficiency, in a large volume of the resection, particularly if it is combined with thoracoplasty. A transsternal approach in one-stage bilateral resections is indicated when the upper parts of the lung must be resected in a large volume, in cases in which difficulties in exposure of the lungs are not expected; one-stage opening of both pleural sacs is recommended in this case for adequate inspection of the lungs before their resection. PMID- 2223231 TI - [Experimental evaluation of different methods of intraoperative aerostasis in surgery of the lungs]. AB - The work deals with the results of comparative evaluation of different variants of intraoperative aerostasis by means of glue and bioplastic materials in experiments on 75 animals. The authors give in detail a clinicomorphological characteristics of each method for rendering the lung wound airtight. It is concluded from the obtained data that aerostasis by means of fibrin glue and collagenous film is highly effective. PMID- 2223232 TI - [Injury to the posterior wall of the left ventricle during mitral valve prosthesis]. PMID- 2223233 TI - [Surgical correction of preductal aortic coarctation in combination with hypoplasia of the aortic arch and patent ductus arteriosus]. PMID- 2223234 TI - [Prostaglandins as a means of emergency aid in critical stenosis of the pulmonary artery]. PMID- 2223236 TI - [A hemangioma of the hourglass type]. PMID- 2223235 TI - [Staged surgical treatment of incompetence of the stump of the main bronchus and a bronchial fistula following pulmonectomy on account of lung cancer]. PMID- 2223237 TI - Cytotoxic activity against HIV-infected monocytes by recombinant interleukin 2 activated natural killer cells. AB - Natural killer (NK) cells have long been known to aid in the control of viral infections by killing virus-infected cells, including those infected with human immunodeficiency virus (HIV). Among the possible NK-susceptible target cells in an infected individual, the monocyte/macrophages are of special significance since they may serve as both a reservoir of HIV and aid in dissemination of the virus throughout the body. A new technique for the enrichment and cultivation of large numbers of recombinant interleukin 2 (rIL-2)-stimulated NK cells has been developed which provides cells with high cytotoxic activity. These IL-2-activated NK cells, adherent lymphokine-activated killer cells (A-LAK), can kill monocytes infected with HIV for 24 h to 7 days, with optimal target sensitivity between 3 and 7 days. Recognition and killing of the infected monocytes did not appear to be restricted by the major histocompatibility complex (MHC) antigens and could be cold-target inhibited by tumor cell lines. A-LAK cells may be useful in newer therapeutic approaches to treatment of HIV infection. PMID- 2223238 TI - Macrophage tropism of HIV-1. AB - Both in vivo and in vitro studies clearly demonstrate that cells of the mononuclear phagocyte lineage are major hosts for human immunodeficiency virus type 1 (HIV-1) replication. Presumably these cells play a key role in the pathogenesis of acquired immunodeficiency syndrome (AIDS). To further delineate the interactions between HIV-1 and host cells, the susceptibility and permissivity of normal human peripheral blood-derived monocyte/macrophages (M/M) and T lymphocytes, and neoplastic monocytoid and lymphoid cell lines to various HIV-1 isolates was assessed. The results suggest: (1) "fresh" isolates recovered from patients and propagated only in normal host cells exhibit a dual tropism for both M/M and T cells, regardless of their tissue of origin or the cell type from which they were isolated; (2) the repeated passage of an HIV-1 isolate through normal M/M does not generally result in the loss of the ability to infect normal T cells nor vice versa; (3) the majority of fresh HIV-1 isolates do not infect neoplastic cells of either origin, and those that do show no preference for monocytoid or lymphoid targets, regardless of their cell origin. PMID- 2223239 TI - Extrachromosomal HIV-1 DNA in persistently infected U937 cells. AB - Persistent human immunodeficiency virus type 1 (HIV-1) infection of U937 monocytic cells resulted in the accumulation of novel forms of extrachromosomal viral DNA. These DNA species are larger than the genome size of HIV-1 and persist indefinitely. The extrachromosomal viral DNA species (E-DNA) were shown to be structurally stable by subcloning of infected cell lines and restriction fragment analysis. Similar E-DNA structures were observed in independent infections. Persistently infected monocytic cells had low levels of viral antigens, reflecting the low levels of viral RNA that were detected. These results support a role for E-DNA in persistent HIV-1 infection of monocytic cells. PMID- 2223240 TI - Effects of GLQ223 on HIV replication in human monocyte/macrophages chronically infected in vitro with HIV. AB - GLQ223 is a formulated version of tricosanthin, a single-chain ribosome inactivating protein that was shown in earlier studies to inhibit human immunodeficiency virus (HIV) replication in T-lymphoblastoid cells and to decrease HIV p24 levels in HIV-infected monocyte-derived macrophages as measured by flow cytometry. The current studies were performed to test the selectivity of the observed inhibitory effects on HIV replication in chronically infected macrophages infected in vitro. Peripheral blood-derived monocyte/macrophages were infected in vitro and cultivated in suspension for at least two weeks prior to GLQ223 treatment. Anti-HIV effects were quantitated by measurement of cytoplasmic HIV p24, by both enzyme-linked immunosorbent assay (ELISA) and flow cytometry and HIV RNA levels were measured by slot blot analysis. Incorporation of [3H]leucine into trichloroacetic acid- (TCA) precipitable protein was also evaluated as an index of nonspecific inhibitory effects mediated by the compound in infected and uninfected cultures. Five days after a single 3-h treatment with GLQ223 there was a concentration-dependent decrease in all measurable HIV parameters within infected cultures. The anti-HIV effects persisted at least 28 days without evidence for increasing HIV expression. GLQ223 treatment of parallel uninfected macrophage cultures showed no significant inhibition of tritiated leucine uptake. These experiments demonstrate that a single pulsed exposure with GLQ223 of macrophages infected with HIV in vitro caused a sustained, concentration dependent decrease in both HIV p24 antigen levels as well as HIV RNA without causing measurable toxicity in uninfected cultures. PMID- 2223241 TI - Ability of anti-HIV agents to inhibit HIV replication in monocyte/macrophages or U937 monocytoid cells under conditions of enhancement by GM-CSF or anti-HIV antibody. AB - Monocyte/macrophages (M/M) are an important target cell for human immunodeficiency virus (HIV) infection in the body. The study of HIV infection in these cells, however, is rather complicated because they represent a variable population, and because HIV entry and replication in M/M may be markedly influenced by a number of factors. These must be considered in therapeutic approaches to HIV infection. In the present set of experiments, we studied the interaction between certain agents which increase the infection of monocyte/macrophages (M/M) by HIV and two groups of anti-HIV agents: dideoxynucleosides and specific inhibitors of gp120-CD4 binding. We found that the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which markedly enhances HIV replication in M/M, does not affect the activity of recombinant soluble CD4 (sCD4) or OKT4A, two agents which block gp120-CD4 binding. However, it had varying effects on different dideoxynucleosides: GM-CSF increased the net anti-HIV activity of 3'-azido2',3'-dideoxythymidine (AZT), while at the same time it reduced the activity of 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI). These effects probably represent an interplay between varying effects of GM-CSF on drug entry and phosphorylation. In additional experiments, we showed that very low concentrations of anti-HIV antibodies could enhance HIV infection of the U937 monocytoid cell line. Interestingly, while this effect has been hypothesized to occur through a CD4-independent mechanism, we found that the anti-HIV activities of both sCD4 and OKT4A were unchanged under conditions of enhancement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223242 TI - Role of the monocyte-macrophage in influenza virus infection of lymphocytes: implications for HIV infection. AB - Knowledge of the pathogenesis of viruses which are less virulent than human immunodeficiency virus (HIV) may provide valuable insights into the pathogenesis of HIV infection. Influenza virus, an enveloped RNA virus, infects monocyte macrophages, although the infection is brief and abortive. Isolated purified lymphocytes are completely resistant to infection. In contrast, mixtures of lymphocytes and macrophages can synthesize all virus proteins. Infection requires physical association of monocyte-macrophages and lymphocytes in "clusters." These studies with influenza virus suggest that the pathogenesis of virus infections in mixed cell cultures may be very different from that observed in purified cell populations, and they suggest that similar studies should be performed with HIV. PMID- 2223243 TI - Macrophages as susceptible targets for HIV infection, persistent viral reservoirs in tissue, and key immunoregulatory cells that control levels of virus replication and extent of disease. AB - Although macrophages are major targets for human immunodeficiency virus (HIV) infection in vivo, study of HIV-macrophage interactions in vitro was hindered because many laboratory strains of HIV would not replicate in macrophages, and because survival of macrophages in culture was poor. Addition of purified macrophage colony-stimulating factor (M-CSF) to cultured macrophages markedly improves their survival, but does not induce proliferation. HIV isolates that replicate in macrophages will also replicate in lymphocytes; however, isolates adapted to lymphoid cells (such as HIV-HTLVIIIB) will not replicate in macrophages. The envelope gene appears to be a major determinant of the cell tropism of viral isolates. T-cell grown virus stocks synthesize abundant gp120, while virus grown in macrophages contains relatively much less gp120. Electron microscopy of virions from macrophages shows them to be depleted of gp120 surface "spikes." Recombination studies show that the portion of the genome coding for the envelope glycoprotein appears to determine cell tropism. Lastly, rsCD4 neutralized macrophage-tropic isolates less efficiently than T-cell tropic isolates. HIV replication in macrophages is partially under the control of cellular factors, although these have been less well characterized than they have in lymphocytes. PMID- 2223244 TI - The effect of interleukin 4 (BSF-1) on infection of peripheral blood monocyte derived macrophages with HIV-1. AB - The effects of various cytokines were examined in an in vitro model of human immunodeficiency virus type 1 (HIV-1) infection of human peripheral blood monocyte-derived macrophages (MDM). Monocytes were obtained from blood of normal donors by Ficoll/hypaque gradient centrifugation and adherence. These cells were allowed to mature in the presence of varying concentrations of cytokines. After five days in culture, cells were harvested, counted, and inoculated with S5G7, an HTLV-IIIB subclone. The cells were replated in the presence of the same concentrations of cytokines. Culture supernatants were sampled over 28 days for p24 antigen (Ag) as measured by Ag capture assay. In repeat experiments, the following observations were made: 1. MDM from some donors could be infected only in the presence of tumor necrosis factor-alpha (TNF-alpha), granulocyte/macrophage colony-stimulating factor (GM-CSF) or interleukin 4 (IL 4); 2. The effect of GM-CSF was variable; TNF alpha also enhanced HIV replication above controls; 3. IL-4 was the most potent enhancer of HIV-1 replication in MDM of the cytokines tested, inducing p24 Ag levels 75-230 times those seen in control cultures run simultaneously. This effect was dose dependent. Ag production was not observed until Day 14 postinfection in most experiments. Multinucleated giant cell formation was observed only in the presence of IL-4. PMID- 2223245 TI - Antibody-enhanced infection of monocytes as the pathogenetic mechanism for severe dengue illness. AB - Antibody-dependent enhancement of certain virus infections can occur in cells expressing Fc receptors. This mechanism plays an important pathogenetic role in the development of complications associated with dengue virus infection, including dengue hemorrhagic infection and dengue shock syndrome. The virulence of the virus, characterized by the ability to infect Fc receptor-bearing monocytes also influences the development of these severe illnesses. PMID- 2223247 TI - [Incidence of epidermoid cancer of the esophagus in Asturias (1975-85)]. AB - We present the incidence the esophageal squamous cell carcinoma in Asturias, based on the review of the clinical histories of eleven years (1975-85). Of 356 total cases, 92.4% were male patients and the remaining 7.6% females; the relation M:F was 12.2:1. Mean age at the time of diagnosis was 59.4 +/- 9.6 for males and 70 +/- for females. Total annual incidence was 2.8 +/- 0.8 cases/10(5) + population/year. Maximal annual incidence was registered in 1981: 1.1 cases/10(5) population/year. Asturias has eight health districts; those with highest incidence were mining areas: Mieres, Cangas de Narcea and Riano. Compared to that of some developing countries, the incidence of esophageal cancer in Asturias is low, similar to that in European countries (except France) and white population of the USA; there is an aggregation of cases in males living in mining areas. PMID- 2223248 TI - [Smoking and serum gastrin and pepsinogen I levels in patients with duodenal ulcers]. AB - At present the mechanisms by which the use of tobacco produces a damaging effect on duodenal ulcerous disease are not clearly understood. This paper reports the results of a study of basal and postprandial gastrin and pepsinogen I (PG I) levels of 74 duodenal ulcer (DU) patients and 18 controls in relation to their smoking habits. There was no difference between the UD group and the control group as far as basal gastrin levels were concerned, but there was in the PG I levels (107 +/- 54 ng/ml in UD vs. 69 +/- 30 ng/ml in control) (p less than 0.05). The postprandial gastrin and PG I responses in 34 UD subjects only differed in relation to smoker/non-smoker status; there was no correlation with age less than greater than 35, positive family history or duration of illness. Patients who had had UD less than 10 years showed higher postprandial PG I levels; however, this group included the 83.3% smokers with UD. It was concluded that chronic smoking is clearly related to the existence of hyperpepsinogenemia I, and probably also to postprandial hypergastrinemia in UD sufferers. PMID- 2223249 TI - [Surgical treatment of gastric cancer. Evaluation of results in 313 consecutive cases]. AB - The results of 313 gastric adenocarcinomas, treated by the same surgical team during 10 years have been evaluated retrospectively. The pathological characteristics, operability (88.8%) and resectability (69.8%) rates, surgical technique and morbility and mortality rates are analyzed. The causes of late mortality, total five-year survival, depending on the stage of the tumors, and survival in relation to treatment are reported. PMID- 2223246 TI - FcR-mediated enhancement of HIV-1 infection by antibody. AB - Although CD4 is a major receptor for human immunodeficiency virus (HIV) infection of cells, studied by ourselves and others clearly show that the Fc receptor (FcR) also plays a role in infection, perhaps in conjunction with other surface receptors. IgG antibodies to HIV-1 will enhance infectivity in cells (such as monocyte-macrophages) that have surface Fc receptors; F(ab')2 fragments of antibodies did not enhance, and blocking of FcR inhibited enhancement. The high affinity FcR for IgG (Fc gamma RI) appeared to be functional. Sera from HIV-1 infected patients had neutralizing activity at high concentrations, but enhanced infection at low concentrations (i.e., high dilutions). Our studies show that the CD4 receptor is required for antibody-mediated enhancement of infection, as enhancement can be blocked by recombinant soluble CD4 and by Leu3 antibody. Although enhancement can be demonstrated in vitro, the in vivo importance of enhancing antibodies remains to be defined in HIV-1 infection. PMID- 2223250 TI - [Percutaneous cholecystostomy guided by ultrasonography. A preliminary experience]. AB - Surgical cholecystostomy is a palliative treatment for cholecystitis and distal biliary obstructions when the general condition of the patient does not allow complex techniques. Percutaneous cholecystostomy (PC) guided by ultrasonography is an alternative to that procedure as well as a method of direct access to the biliary tract for diagnostic examinations (bacteriologic study of bile and percutaneous cholangiography). During one year, 9 female patients, mean age 74 (49 to 90) underwent this approach; 5 patients had cholecystitis, 2 were suspicious of biliary sepsis and 2 had angiocholitis. Because of poor general condition, no other approach was possible in any of the cases. There were no relevant complications. All 5 cases of cholecystitis improved after the procedure although 3 patients died within 30 days of causes unrelated to PC. In two cases biliary sepsis was ruled, and the probe was withdrawn, without complications. The two patients with angiocholitis improved significantly; in both cases it was shown that the cause was cholelithiasis: later on, they were treated by different methods (endoscopic sphincterotomy in one case and surgery in the third case). These preliminary results suggest that PC guided by echography should be included as a routine therapeutic and diagnostic method in the management of digestive diseases. PMID- 2223251 TI - [Absence of effect of atropine on exocrine pancreatic secretion stimulated by cerulein]. AB - The effect of atropine, 0.9, 1.8, 7 and 29 nmol/kg-1/h-1, on pancreatic exocrine secretion has been measured in seven dogs with gastric and pancreatic fistula in response to IV administration of increasing doses of cerulein (3.7 to 118 pmol/kg 1/h-1). Secretin was perfused continuously, at a rate of 20.5 pmol/kg-1/h-1, starting one hour before perfusion of cerulein. The administration of atropine, 7 and 29 nmol/kg-1/h-1, significantly (p less than 0.05) decreased the protein response to secretin. Only the injection of 29 nmol/kg-1/h-1 of atropine produced a significant decrease in the secretion of bicarbonate in response to secretin. The administration of 3.7 pmol./kg-1/h-1 and larger doses of cerulein significantly increased the secretion of bicarbonate and protein, compared to the levels obtained with the administration of secretin alone. None of the atropine doses showed a significant effect on the pancreatic response to the administration of cerulein. Only the highest dose of atropine, 29 nmol/kg-1/h-1, modified cardiac rate. These findings are consistent with the hypothesis that cholinergic innervation does not modify the effect of cerulein, a CCK analogue, on the pancreatic secretion of protein and bicarbonate in the dog. PMID- 2223252 TI - [A model of experimental acute pancreatitis in the conscious rat]. AB - We describe an experimental model of acute pancreatitis in conscious rats, based on biliary reflux; sodium deoxycholate was injected while maintaining the common duct (biliary and pancreatic) temporally occluded. A progressive increase of serum amylase, cardiac rate and hematocrit value, as well as a decrease of plasma proteins are characteristic of this experimental model. Blood pressure was maintained until shortly before death, which occurred after 85 minutes. This is a simple model, reliable and reproducible, which requires minimal surgical manipulation. PMID- 2223253 TI - [Morgagni's hernia. A case report]. AB - A case of Morgagni's hiatal hernia is presented. Because of clinical symptoms (dizziness and chest pain) the patient was referred to the Cardiology Department and the diagnosis was a casual finding. The hernia sac contained transverse colon, great omentum and round ligament. We comment on the mechanism, etiologic factors, diagnosis, and surgical treatment. The present case was treated by an abdominal approach. PMID- 2223254 TI - [Intra-arterial infusion with urokinase for embolism of the superior mesenteric artery]. AB - We report the case of a 65 year old male patient in whom an early diagnosis of embolism of the superior mesenteric artery was made and successfully treated by an intraarterial infusion of urokinase. PMID- 2223256 TI - [Hemangiopericytoma of the rectal mesentery]. AB - The authors present a case of hemangiopericytoma of the rectal mesentery, this is an uncommon type of vascular tumor, exceptional in this localization. We analyze the difficulty of a preoperative diagnosis, the lack of specificity of the clinical signs and the importance of the radical resection linked to the biological aggressiveness and the frequency of local recurrences and distant metastases. PMID- 2223255 TI - [Torsion of an ectopic spleen as a cause of acute abdomen]. AB - A case of torsion of an ectopic spleen is presented. Diagnosis was obtained by echography, CAT and arteriography. We review the cases reported in literature and discuss the diagnostic and therapeutic problems raised by this rare condition as the cause of acute abdomen as well as for the differential diagnosis of abdominal masses. PMID- 2223257 TI - [Peroxisomes and neurological disorders]. PMID- 2223258 TI - [Neurophysiological study on hemifacial spasm--the abnormality and origin of the electromyographic response to stimulation of the facial nerve]. AB - Electromyographic responses (MD-OC) of the orbicularis oculi muscle to stimulation of ipsilateral marginal mandibular branch of the facial nerve were recorded in 20 patients with hemifacial spasm, pre-, post-operatively and during operations to relieve it by microvascular decompression, and the abnormal features and origin of the MD-OC were investigated. On the affected side, the MD OC were recorded in pre- and during operative state, and disappeared with disappearance of hemifacial spasm after microvascular decompression, while no response was recorded in pre-, during and post-operative state on the healthy side. In 17 patients, the MD-OC was recorded continuously during operation. In all cases except for one case in whom the MD-OC was recorded even the end of operation, the MD-OC disappeared on several stage of procedure from dural opening through vascular mobilization. The compound nerve action potential (MD-VII) to stimulation of the marginal mandibular branch was recorded from the facial nerve near its root entry zone after exposure of the intracranial portion. There were two patterns in the records, i.e., one group consisting of early component and the other consisting of early and late component. The MD-VII was only consisted of the early component in 12 cases in whom the MD-OC have already disappeared, and was consisted of the early and late component in 5 cases in whom the MD-OC still recorded. And in 2 cases of the later, the late component disappeared simultaneously with disappearance of the MD-OC during vascular mobilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223259 TI - [Resemblance of magnesium and zinc distribution in soft tissues and bone of rats fed unbalanced mineral diets in situ]. AB - Although the role of zinc (Zn) and magnesium (Mg) in situ may be of a critical importance in replication, transcription and repair of DNA, to our knowledge, the relationship between Mg and Zn has been described. This study, therefore, was designed experimentally to investigate the relationship between Mg and Zn in soft tissues and bone of rats after fortification of unbalanced mineral diets, and minerals and metals in soft tissues and bone were determined by inductively coupled plasma emission spectrometry. In the groups fed low calcium (Ca) diet, low Ca-Mg diet and low Ca-Mg plus high Al diet, serum Mg level was lower in the group fed low Ca-Mg diet and low Ca-Mg plus high Al diet than those in the groups fed standard diet and low Ca diet. However, there was no significant difference in Mg content of CNS tissues in rats fed unbalanced and standard diets except for that in the spinal cord of rats fed low Ca-Mg plus high Al diet. Whereas, Zn content of CNS showed lower values in the unbalanced mineral diet groups, especially in all CNS regions of the low Ca-Mg plus high Al diet group, than those in the standard and the low Ca diet group. And Zn contents in heart, kidney and abdominal aorta of rats fed low Ca-Mg diet and low Ca-Mg plus high Al diet were more decreased than those of the standard and the low Ca diet groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223260 TI - [Changes in epidural pulse pressure in brain edema following experimental focal ischemia]. AB - It is well known that epidural pulse pressure (PP) increases with rising intracranial pressure (ICP). However, PP at the same ICP is not always identical in various intracranial pathologies. Many authors have investigated PP at increased states of ICP, but few studies related to brain edema have been done. This study was carried out in order to clarify the changes of PP in brain edema following focal ischemia. ICP and PP were measured in two groups of anesthetized dogs; 1) increased volume of CSF by cisternal saline injection (control, n = 5), 2) brain edema caused by focal ischemia (edema, n = 11). Ischemia was induced by electro-coagulation of the right anterior cerebral artery and by clipping the right middle cerebral artery and right internal carotid artery transorbitaly. The brain was recirculated for 6 hours after 2 hours of ischemia. The ischemic areas were identified by Evans blue, triphenyl tetrazolium chloride (TTC) or histological examination. Water content of the brain was measured by the wet-dry weight method. The canine focal ischemic model showed consistent ischemic damage in the caudate nucleus and produced brain edema successfully. PP increased linearly with rising ICP to 35 mmHg, and PP in the edema group was significantly smaller than that in the control group at the same ICP value. The slopes of the regression equation of ICP and PP were significantly different between the edema and control group (edema: 0.061 +/- 0.030, control: 0.107 +/- 0.015, mean +/- SD, p less than 0.01). These results suggest that PP is easily affected by ischemic brain edema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223261 TI - [A case of syphilitic meningitis presenting the seventh nerve and the eighth nerve palsies]. AB - Here we described a case of syphilitic meningitis presenting the seventh nerve and the eighth nerve palsies. A 56-year-old man was admitted because of left facial palsy and hearing loss of bilateral ears. He had a penile chancre five months before admission. Cerebrospinal fluid examination showed high pressure, pleocytosis predominantly with mononuclear cells and high protein content. STS and TPHA of serum and CSF were positive. High dose penicillin G was effective, and he was discharged with only mild hearing loss in the left. Considering the penetration of penicillin G into the CSF and the minimum fully treponemicidal concentration of penicillin, the administration of large doses of aqueous penicillin G intravenously or intramuscularly was effective in such a case to prevent permanent deafness, though CDC recommends relatively low dose. PMID- 2223262 TI - [Infarction in the territory of the anterior choroidal artery due to embolic occlusion of the internal carotid artery--report of two cases]. AB - A case with infarction in the territory of the anterior choroidal artery (AChA) due to embolic occlusion of the internal carotid artery (ICA) is rare. We described two cases and investigated the mechanism of the territory of the AChA. Case 1 was a 69-year-old man. Case 2 was a 71-year-old woman. The neurological examination in both cases showed left homonymous hemianopsia, left facial palsy, left hemiparesis and left hemisensory disturbance. CT scan in these cases showed infarctions of the right uncus, amygdaloid nucleus, genu and posterior limb of the internal capsule, globus pallidus, lateral geniculate body and tail of the caudate nucleus. The right common carotid angiogram showed a complete occlusion of the ICA at its cervical segment in case 1 and at its carotid siphon in case 2. In both cases, the left carotid injection visualized the right anterior cerebral artery and right middle cerebral artery via the anterior communicating artery well, but the right AChA was not visualized. In case 1, the collateral pathways from the right external carotid artery (ECA) and the right posterior communicating artery (PCoA) to the right ICA were not supplied and the precommunicating segment of the right posterior cerebral artery was hypoplastic. In case 2, the collateral pathway from the right ECA to the right ICA was not supplied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223263 TI - [Effect of dilazep on experimental vasospasm--evaluation of angiographical vasospasm and cerebral blood flow]. AB - The effects of dilazep dihydrochloride on angiographic vasospasm and regional cerebral blood flow after subarachnoid hemorrhage were evaluated in double hemorrhage canine model. Severe angiographic vasospasm of basilar artery (percent reduction of intra-luminal diameter; 52.4%) was shown in untreated dogs. Daily intra-venous administration of dilazep (0.3 mg/kg for one hour) significantly inhibited angiographic vasospasm (percent reduction of intra-luminal diameter; 33.2%, p less than 0.05). Dilazep had a marked vasodilatory effect even in severe vasospasm in untreated dogs, and had a tendency to increase cerebral blood flow of the cerebral cortex in spite of reduced blood pressure. From these characteristics of action, intra-venous administration of dilazep would be useful agent for the treatment of cerebral vasospasm after subarachnoid hemorrhage. PMID- 2223264 TI - [Multiple hemorrhagic cerebral amyloid angiopathy associated with leukoencephalopathy]. AB - The authors present a case of cerebral amyloid angiopathy (CAA) which caused multiple recurrent subcortical hemorrhages and leukoencephalopathy similar to Binswanger's disease. CT scan revealed bilateral hypodensity of the hemispheric white matter in addition to multiple subcortical hemorrhages. The difference between white and gray matter densities was 14 approximately 15 HU. T2-weighted MRI showed the hemispheric white matter as high intensity. These findings on CT and MRI are compatible with those observed in leukoencephalopathy like Binswanger's disease. A biopsy of the cortex was performed and histological examination revealed amyloid deposition in the arterial wall. In addition to amyloid deposition, obliterative intimal proliferation and hyaline degeneration of the vessel were observed. It is thought that the occlusive vascular change due to CAA may induce chronic hypoperfusion of the hemispheric white matter and consequently the leukoencephalopathy may develop. In the aged population, CAA is noteworthy as a cause of both hemorrhagic and ischemic lesions, because the incidence of CAA is increasing with age. PMID- 2223265 TI - [Biochemistry of mitochondrial encephalomyopathy]. PMID- 2223266 TI - [A case of solitary thalamic abscess treated by sterotactic aspiration]. AB - The Solitary thalamic abscess appears to be uncommon, 17 cases have been reported since 1973. We successfully treated a case of thalamic abscess associated with diabetes mellitus by sterotactic aspiration with external drainage. A 55 years old man presented right hemiparesis. A computed tomographic (CT) scan revealed solitary thalamic low density lesion with ringed contrast enhancement. We started the administration of antibiotics, but on the 9th day he became drowsy and his eyes were deviated downward and inward. CT scan on the 10th day showed the edema had been spread to the tectum. We aspirated purulent fluid material with confidence by sterotactic operation. We considered the mid brain tectum to be responsible for the downward and medial deviation of the eyes, because it appeared only when the edema and abscess were spread to that area, and disappeared after aspiration of the abscess with subsidence of the edema. PMID- 2223267 TI - [Effects of unilateral temporal lobectomy on verbal dichotic listening test]. AB - Verbal dichotic listening test was conducted before and after anterior temporal lobectomy on 25 patients who underwent the operation because of their medication resistant epileptic seizures. Their speech dominance by Wada test was all left sided. 1. Preoperatively, patients having the epileptogenic focus in the right temporal lobe (R-TLE) and those having the focus in the left (L-TLE) were, as expected, all right-ear dominant. The mean number of correct responses was fewer in L-TLE than in R-TLE group. 2. Postoperatively, no detrimental effects for recognition of verbal auditory stimuli by the ear contralateral to the focus was observed both in L-TLE and in R-TLE group. 3. Postoperatively, the ear-dominance shifted: to the left in patients with L-TLE, and to the right more conspicuously in patients with R-TLE compared to the preoperative scores. In other words, the recognition ability by the ears ipsilateral to the side of focus, or of resected temporal lobe, was ameliorated. Summarizing, the unilateral anterior temporal lobectomy did not cause "lesion effect" but yielded improvement of verbal auditory recognition by ears ipsilateral to the epileptogenic focus. Diminished epileptic bombardment resulted in by the resection surgery may be a possible explanation. PMID- 2223268 TI - [Disturbances of visual perception and the lesions on spastic diplegia]. AB - In a study of 12 cerebral palsy with spastic diplegia, the relationship between their disturbances of visual perception and their lesions was discussed. All of them were performed Frostig Developmental Test of Visual perception and Tanaka Binet Intelligence Test. Six of them showed disturbances of visual perception on Frostig Test. Subtest II, figure-ground, was the lowest of all subtests. The mean of perceptual quotient was under that of intelligence quotient significantly (p less than 0.05 t-test). MRI examination was performed to all and the lesions were detected at 10 of them. Six who showed disturbances of visual perception had the lesions and two who showed good visual perception had no lesions. The lesions were periventricular white matter and extended to semioval center and subcortical white matter at parietal and occipital lobes. Anatomically, their lesions correspond to superior longitudinal bundle and vertical occipital bundle and their bundles have important functions as the pass way of visual perception. Therefore, it was suggested that the disturbances of visual perception detected at spastic diplegia were based on the lesions and the mechanism was disconnection of higher visual pass way. PMID- 2223269 TI - [Aging effect on frontal lobe function-evaluation by the new modified Wisconsin Card Sorting Test]. AB - New Modified Wisconsin Card Sorting Test (WCST) was administered to ninety-five individuals to assess the effects of age on frontal lobe functions. The correlations between ages and scores were evaluated in the following five subgroups which were classified into whole subjects (TOL, n = 95), normals and patients who were neurologically diagnosed as only having cervical spondylosis (NOR, n = 20), individuals whose age-corrected total intelligence quotients (TIQ) by the Wechsler Adult Intelligence Scale were higher than or equal to 100 (HIQ, n = 30), individuals whose TIQ were less than 100 (LIQ, n = 27), and individuals whose Mini-Mental State Examination scores were full (MMS, n = 28). Scores of the WCST including Categories Achieved, Total Errors, Difficulty of Maintaining Set and Perseveration were significantly correlated to ages in four groups such as TOL, NOR, HIQ, and MMS. The correlation of WCST's scores of the four groups indicated almost the same tendency. Some subcategories of the WCST, indicating perservation which were characteristic signs of the frontal lobe dysfunction correlated with ages in these four groups. The groups indicating NOR, HIQ, and MMS were thought to be regarded as being normal controls. And, the scores of Mini Mental State Examination were not correlated with ages. So, the WCST scores of the MMS group were no thought to be effected by the age-related decline of intelligence. The results might suggest that the age-related decline of the frontal lobe function precedes that of intelligence. PMID- 2223270 TI - [Alteration of prolactin secretion after transsphenoidal adenomectomy for prolactinomas]. AB - The author studied the dynamics of prolactin (PRL) secretion after adenomectomy, and considered the treatment for prolactinomas. The study group comprised a total of 74 patients with prolactinomas who underwent transsphenoidal surgery between 1979 and 1986, and 61 patients out of them were followed up more than one year. Post-operatively, hyperprolactinemia was cured (under 20 ng/ml) in 19 of 36 microadenomas (53%), and 7 of 38 macroadenomas (18%). Pre-operatively, PRL response to TRH was blunt except 3 patients, but it recovered in 16 patients after surgery, and 5 more patients during follow-up. Recurrence of hyperprolactinemia occurred in only one of 19 patients who were followed up more than one year, and she was not a PRL responder to TRH. Bromocriptine was administrated to 46 patients after surgery, and hyperprolactinemia was restored to normal in 40 patients. And in 7 patients whose basal PRL levels were between 23 and 41 ng/ml after surgery, hyperprolactinemia was cured still after withdrawal of bromocriptine. During pregnancy, PRL levels were relatively low in surgically cured patients, but in most of others they became over 200 ng/ml promptly after withdrawal of bromocriptine. Recurrence of hyperprolactinemia was rare, and PRL response to TRH recovered in most of surgically cured patients. Even if it is not cured surgically, lowered PRL levels have a good effect on the additional bromocriptine therapy. I prefer transsphenoidal surgery in respect of curative treatment for prolactinomas. PMID- 2223271 TI - [Thrombus propagation and venous drainage disturbance in cerebral sinus-vein thrombosis--38 autopsied cerebral sinus-vein thrombosis]. AB - 38 autopsied cases of cerebral sinus-vein thrombosis (CSVT) in our institute were studied. In this study, special attention was paid for the evolution and fate of venous thrombus. 18 cases showed hemorrhagic infarction or intracerebral hematoma (group 1; G 1). In contrast, no cerebral parenchymal changes were observed in the other 20 cases (group 2; G 2). In 13 of 18 cases of G 1, superior sagittal sinus (SSS) were thrombosed. 10 of these 13 cases showed thrombosed cerebral cortical veins (CV) or deep cerebral veins (DV). In contrast, none of 16 cases of G 1 with thrombosed SSS showed thrombosed CV or DV. All cases of the solitary thrombosis of CV or DV (each 2 cases) belong to G 1. Venous thrombi were divided into three stages according to its process of organization; recent thrombus (R), hyalinized thrombus (H), organized thrombus (O). In the venous thrombi of G 1, 6 cases were R, 6 were partly H, 6 were partly 0. In addition to O, R and H were also observed in group O. Distribution of various stage of thrombus in same case suggested that gradual thrombus evolution had occurred before or after the clinical onset in CSVT. This study suggested: (1) CV or DV occlusion may play an important role for the advent of cerebral parenchymal changes in CSVT. (2) Gradual thrombus evolution after the onset is one of possible causes of slow clinical deteoration after the onset. Therefore, prevention of these thrombus propagation with anti platelet drugs or fibrinolotic therapy should be recommended for the treatment of CSVT. On the contrary, hyperosmolar agents and diuretics may produce potential risk of dehydration, and as a result, accelerate secondary thrombus extension. PMID- 2223272 TI - Menarcheal age and endemic goitre. AB - A total of 13,566 school girls from 17 districts in Sri Lanka recalled their date of menarche for a study on the prevalence of goitre. Seventy-four percent (10,036) did not have any signs of goitre, and the recalled mean age of menarche for this group was 13.6 years. This figure was significantly lower than the mean age of 13.9 years observed in the goitrous group. The mean age was lowest for thyroid grade 0 and highest for thyroid grades 1b and above. The mean age in high prevalence areas was significantly higher both among goitrous and nongoitrous groups, and in different areas of prevalence the mean age was higher among the goitrous than the nongoitrous. These findings strongly suggest a delay in sexual maturation among girls living in endemic goitre areas and among girls with evidence of goitre. PMID- 2223273 TI - Pattern of medical care services utilization in Fiji. AB - The present study was designed to analyze sociodemographic and health related factors that influence the utilization of medical care services in Fiji by using the method of discriminant function. Some sociodemographic and health related independent variables had significant effects on the two patterns of modern and traditional medical services utilization. Discriminant function coefficients for sex, age and race are large enough to suggest the importance of discriminating between two patterns of medical care utilization. This suggests that traditional medical service is coexistent with modern medicine in Fiji and might play an extremely important role in providing health care for rural communities in the same way as modern medicine. PMID- 2223275 TI - Motorcyclist traffic accidents and risk factors: a Singapore study. AB - Motorcyclist accidents cause significant morbidity and mortality in Singapore. To elucidate personal and environmental factors associated with such accidents, we studied 198 motorcyclists who were hospitalized in Singapore General Hospital between April 1986 and June 1987. The patients were mostly young and almost exclusively male with a high proportion of Malays. Most accidents occurred on Sundays and at night. Ten percent of the victims took alcohol before the accident. Most had low injury severity scores (ISS). Less experienced drivers had a significantly higher ISS than those with one year or longer of driving experience. Vigorous control of drunken driving, through public education and intensive breath testing, should reduce the incidence of traffic accidents. PMID- 2223274 TI - A randomised controlled trial of counseling in a workplace setting for coronary heart disease risk factor modification: effects on blood pressure. AB - This paper reviews a prospective study of occupational factors in coronary heart disease risk incorporated in a randomised controlled trial of a worksite based occupational health nurse counseling program for reducing coronary heart disease risk factors. The aim of the trial was to evaluate the longterm effectiveness of the counseling program in persons with mildly elevated risk factor levels. Of the 2,489 Australian government employees with mildly elevated risk factor levels who entered the intervention trial, 1,937 (78%) attended a followup examination three years later. This paper reports on changes in systolic and diastolic blood pressure. Multiple linear regression models were used with three-year blood pressure reduction as the dependent variable, intervention status as the main determinant, and sex, age, initial risk level and initial blood pressure as covariates. Although systolic and diastolic blood pressure fell in both the intervention and control groups, intervention was significantly associated with systolic blood pressure change only. PMID- 2223276 TI - The leadership challenge of tobacco use in Asia: towards health promotion and health for all. AB - Tobacco use in Asia is sharply on the rise. Present trends in increased smoking behavior will result in epidemics of smoking related diseases and deaths of millions annually in the foreseeable future. Collective leadership for health from several sectors is needed to reverse the trend in increased tobacco use. An agenda for action by leaders is presented, and an intersectoral approach is advocated with a focus on proactive measures to promote positive behaviors for health and to prevent a pandemic of unprecedented proportions. PMID- 2223277 TI - Socioeconomic and health programme effects upon the behavioral management of diarrhoeal disease in northeast Thailand. AB - This study investigates the effects of socioeconomic and health programme factors on preventive and curative health behaviors and assesses the impact of preventive health behaviors on the incidence of diarrhoea among children under five years of age. Methodological approaches included focus groups to uncover local definitions of diarrhoeal disease, a baseline survey which collected data on maternal preventive health behaviors for 1,364 children, and a monitoring system which collected data on the incidence of diarrhoea and on maternal curative behaviors among the same group of children. Results indicate that socioeconomic status and exposure to health programmes showed significant relationships with selected maternal preventive behaviors. Children whose mothers washed their hands before breastfeeding, gave their child food immediately after cooking and warmed foods each time before meals had significantly lower proportions with diarrhoea than children of mothers who did not practice these behaviors, and 70 percent of the children with diarrhoea were exposed to high risk of severe dehydration and related health complications. Implications of these findings for health programmes are discussed. PMID- 2223278 TI - Child survival and beyond. PMID- 2223280 TI - The cultural definition of an infantile diarrhea in Tambon Korat and Koongyang, northeast Thailand: community perceptions in diarrhea control. AB - In Tambon Korat and Koongyang in Northeastern Thailand, 88% (n = 60) of the mothers and significant other careproviders interviewed believe in poh, a mild, self-limiting diarrhea in infants which is considered a normal prerequisite in child development. The local definition of poh as to its nature, symptomatology and home management and implications for diarrhea control activities are presented in this paper. PMID- 2223281 TI - Nutritional problems of Malaysian children and approaches taken to overcome them. AB - Nutritional status of children is an important factor in child survival, especially in developing countries. It is therefore important that nutritional problems are addressed and overcome. This paper reviews the many studies conducted in Malaysia on nutritional problems among children. It also documents the approaches, including intersectoral approaches, that have been taken to overcome these problems. Possible actions that have to be taken in the future to further improve the nutritional status of Malaysian children are discussed. PMID- 2223279 TI - Nutritional intervention: a key to child survival. AB - In a collaborative relationship, researchers from the Cebu Institute of Medicine and from the United States have carried out a series of longitudinal studies of breast feeding and infant growth in a rural Philippine community. On the basis of our findings, we have conducted field experiments designed to have mothers improve their infants' diets using locally available food. Contingent reinforcement strategies were used successfully to get mothers to change their behavior and beliefs about infant feeding practices. The use of reinforcements resulted in improved diets and very high rates of continuation of participation in the field experiments. We believe that this is a highly productive and cost effective way to approach the problem of gaining cooperation and continued involvement in a nutrition intervention effort. PMID- 2223282 TI - Motor vehicle injuries in Taiwan. AB - In Taiwan, motor vehicle fatalities have increased significantly in the past two decades and are now a leading cause of mortality, especially among younger age groups. In this paper, we review vital statistics and hospital morbidity data to provide an overview of the problem of motor vehicle injuries in Taiwan and make several suggestions for improving injury surveillance. PMID- 2223283 TI - The use of the Nabarro Thinness Chart in identifying children for nutrition supplementation in Sri Lanka. AB - This study compares the use of the Nabarro Thinness Chart with other nutritional screening tools among school children in Sri Lanka. It concludes that this method is a simpler, more precise approach to assess students requiring food supplementation in community programmes than others which are commonly utilized. PMID- 2223284 TI - Delivering health care to the Pacific. PMID- 2223285 TI - Reduced funding affects dental schools. PMID- 2223286 TI - 'Surgical emphysema during restorative dentistry'. PMID- 2223287 TI - 'Temporary elective tooth separation as a diagnostic aid in general dental practice'. PMID- 2223288 TI - Intra-oral hair implant: a delayed complication of facial trauma. PMID- 2223289 TI - Working conditions of resident SHOs. PMID- 2223290 TI - 'Supplemental and congenitally absent premolar teeth'. PMID- 2223291 TI - A reappraisal of the value of the bitewing radiograph in the diagnosis of posterior approximal caries. AB - The aim of this paper was to re-assess the available literature examining the value of the bitewing radiograph in the diagnosis of approximal caries and to compare the relative values of radiographic and clinical examinations. To this end, results from 29 research studies have been re-presented and tabulated. These results show that the use of the bitewing radiograph is essential if much approximal caries is not to be missed. It is particularly important in the detection of the small lesion which may be managed preventively rather than operatively. Although there is a proper need to ensure that radiographic exposures are minimised, the evidence suggests that both clinicians and epidemiologists must balance this need with the ethical issues associated with failing to employ an established diagnostic aid. PMID- 2223292 TI - Root caries in older people attending a general dental practice in East Sussex. AB - With increasing numbers of older people retaining their natural dentitions, dentists are becoming increasingly aware of the problem of dental caries occurring on exposed root surfaces--root caries. This study reports the prevalence of root caries in a selected older population, living in the community and attending a general dental practice in Bexhill, East Sussex. A total of 146 non-institutionalised people, aged at least 55 years with at least 12 teeth, were examined. Most of the subjects (88.4%) had evidence of root caries, males and denture wearers having more lesions than females and non-denture wearers, respectively. Active coronal caries was present in only 11.6% of the subjects, whereas active (soft or leathery) root caries lesions were present in 31.5% of the subjects. The teeth and surfaces most commonly affected by root caries were found to be similar to those seen in previous epidemiological surveys. The majority of active root caries lesions were within 1 mm of the gingival margin, while inactive lesions tended to be greater than or equal to 1 mm from the gingival margin. Colour of root caries lesions was not diagnostic of caries activity. A more detailed method of recording root caries lesions is also described. PMID- 2223293 TI - Central neurilemma of the mandible. AB - A rare case of symptomless central neurilemmoma of the mandible is reported. Post operative recovery was uneventful and, in particular, post-surgical paraesthesia was followed by a return to normal sensation. PMID- 2223294 TI - 'The Yankee dodge': some new observations on the discovery of anaesthesia. AB - The discovery of general anaesthesia is arguably the most important advance in the practice of surgery. To whom the credit belongs has, however, remained controversial. A first-hand account has now indicated that this controversy can finally be resolved, and that the credit for the discovery of anaesthesia should be given to Horace Wells. PMID- 2223295 TI - Badges of the dental profession. The International Federation of Dental Anesthesiology Societies. PMID- 2223296 TI - The problems of running a phantom department. PMID- 2223297 TI - Decentralization: problems and approaches. PMID- 2223298 TI - So you think you're different. PMID- 2223299 TI - Endocavitary ablation of atrioventricular conduction. PMID- 2223300 TI - Mitral valve surgery: to repair or replace? PMID- 2223301 TI - Systemic pattern of free radical generation during coronary bypass surgery. AB - Diffuse impairment of ventricular function after cardiac surgery may be related to the generation during reperfusion of the myocardium of free radicals derived from oxygen. Fifteen patients undergoing elective coronary bypass surgery were studied by previously described assays for peroxidised lipids and for isomerised lipids which were used as indices of free radical activity. Serial blood samples were obtained from systemic arterial, mixed venous, and coronary sinus catheters before, during, and after the ischaemic period. The patients underwent coronary artery surgery on cardiopulmonary bypass with a membrane oxygenator, relative hypothermia 30-34 degrees C, and intermittent cross-clamping of the aorta. During the ischaemic periods there were no significant changes in the indices of free radical activity. During the reperfusion phase there was a significant increase in free radical indices in arterial and mixed venous blood. A small rise in free radical indices in coronary venous blood was not statistically significant. These data indicate that free radical activity is increased in patients shortly after the cessation of cardiopulmonary bypass. The pattern of distribution between the different sampling sites suggests that much of the observed increase in isomerised and peroxidised lipids originates from tissues other than the myocardium. PMID- 2223302 TI - Does blood rheology revert to normal after myocardial infarction? AB - After myocardial infarction there is an acute deterioration of the flow properties of blood. The present study was designed to test whether the abnormality persists. Blood and plasma viscosity, red cell aggregation and deformability, haematocrit, erythrocyte sedimentation rate, white cell count, cholesterol, and triglycerides were measured in 51 patients who had had a myocardial infarction 5.4 (mean) years before. Results in patients and controls were compared and matched pairs with identical cardiovascular risk factors were also selected. Blood viscosity and red cell aggregation were increased and red cell deformability was decreased in the 51 patients. The abnormalities were independent of the interval since infarction and persisted for years. The rheological abnormalities present after myocardial infarction are at least partly independent of the acute event and acute phase reactions. They contribute to the reduced perfusion of the microcirculation of the heart. PMID- 2223303 TI - Prospective evaluation of a protocol for induction of sustained ventricular tachycardia in patients referred to a tertiary centre. AB - All eight stages of a stimulation protocol that used one then two extrastimuli from the right ventricular apex in sinus rhythm and three ventricular drive rates (100, 120, and 140 beats/min) were performed in 24 patients with recurrent spontaneous sustained ventricular tachycardia despite drug treatment. Twenty two of the patients had sustained a previous myocardial infarct and 18 were on long term treatment with amiodarone. Sustained (greater than 30 s) ventricular tachycardia was induced in all patients. Two extrastimuli were significantly more likely to induce sustained ventricular tachycardia than one extrastimulus, both overall and individually for the three ventricular drive rates. A ventricular drive rate of 140 beats/min was significantly more likely to induce ventricular tachycardia than ventricular drive rates of 100 and 120 beats/min which were significantly more effective than sinus rhythm. A ventricular drive rate of 140 beats/min with one or two extrastimuli induced ventricular tachycardia in 23/24 (95%) of the patients in this study. The full eight stage protocol was progressive separately for both extrastimuli and ventricular drive rate but the last two stages (ventricular drive rate of 140 beats/min with one or two extrastimuli) were as effective as the entire protocol in inducing ventricular tachycardia. PMID- 2223304 TI - Use of computed tomographic scanning and aortography in the diagnosis of acute dissection of the thoracic aorta. AB - Before the introduction of computed tomographic (CT) scanning, aortography was the investigation of choice for acute aortic dissection. Between 1978 and 1982, 24 patients were referred to the Brompton Hospital with suspected acute thoracic aortic dissection; all had aortography with diagnosis confirmed at surgery (n = 12) or necropsy (n = 2) or supported by clinical outcome (n = 8). One patient in whom aortography was negative had type B dissection at necropsy and another patient was lost to follow up. CT scanning became available in this unit in 1983 and between 1983 and 1987 was used as the only imaging investigation in 32 patients with suspected acute dissection of the thoracic aorta while in a further 22 patients aortography was used alone. Results were confirmed at surgery (n = 18), necropsy (n = 3), or supported by clinical outcome (n = 31). Two patients were lost to follow up. In an additional 16 patients both aortography and CT scanning were performed with concordant findings in 10. In six in whom the results were discordant, aortography was normal in three in whom subsequent CT scanning showed type B dissection and CT scanning was normal in three patients in whom aortography showed type A dissection. Both CT scanning and aortography are reliable techniques for assessment of suspected acute dissection of the thoracic aorta. Both techniques misdiagnose occasionally and the frequency of misdiagnosis will be minimised by performing both investigations in patients where the level of clinical suspicion is high and the initial investigation negative. CT scanning tends to miss type A dissection and in view of the success of surgery in this condition this failing has the more serious clinical consequences. PMID- 2223305 TI - Abnormal diastolic function in patients with type 1 diabetes and early nephropathy. AB - Left ventricular diastolic function was assessed by pulsed Doppler echocardiography in non-diabetic controls (n = 11) and in patients with type 1 diabetes without microvascular disease (n = 16; diabetic controls), with microalbuminuria (n = 9), or with early persistent proteinuria (n = 11). The peak filling velocities during the early and atrial phases of left ventricular diastole and their ratio (E:A ratio) were measured. All patients with diabetes had a normal serum concentration of creatinine and exercise electrocardiogram. The mean E:A ratio was significantly lower in those with proteinuria than in the diabetic controls because of an increase in peak atrial filling velocity; most patients with proteinuria had an abnormal E:A ratio of less than 1.0. Multiple regression analysis showed that systolic blood pressure was the major determinant of both the peak filling velocity during the atrial phase of diastole and also left ventricular mass. Blood pressures were significantly higher in the proteinuria group than in the diabetic controls. Glycaemic control and autonomic function did not influence diastolic filling. The slightly raised blood pressures at the earliest stages of diabetic nephropathy are sufficient to alter left ventricular diastolic compliance--this may reflect early hypertensive heart disease. These data do not preclude a specific heart muscle disease related to diabetes, but suggest that these slightly raised blood pressures contribute significantly to left ventricular dysfunction in these patients, in whom the risk of cardiovascular disease is already greatly increased. PMID- 2223306 TI - Doppler echocardiographic evaluation of pulmonary artery flow after modified Fontan operation: importance of atrial contraction. AB - Doppler echocardiography was used to evaluate blood flow in the pulmonary artery in 14 patients 2 to 42 months (mean (SD) 17 (12) months) after a modified Fontan operation incorporating a direct atriopulmonary anastomosis. Preoperatively six patients had tricuspid atresia, six had a double inlet left ventricle, and two had pulmonary atresia with an intact ventricular septum. The postoperative rhythm was sinus in 11 patients, junctional in one, ventricular pacing in one, and atrioventricular sequential pacing in one. In one patient the Doppler trace was unsatisfactory for analysis. In all patients forward flow in the pulmonary artery had biphasic peaks related to both atrial and ventricular contraction. The mean (SD) peak flow velocity that was synchronous with atrial contraction was 80 (30) cm/s and that synchronous with ventricular contraction was 74 (23) cm/s. The atrial contribution to total pulmonary artery flow, assessed by velocity-time integrals, varied between 22% and 73% (mean (SD) 45 (14)%). In patients with tricuspid atresia the mean (SD) peak flow velocity with atrial contraction was 90 (27) cm/s and that with ventricular contraction was mean (SD) 68 (24) cm/s. In patients with double inlet left ventricle the mean (SD) peak flow velocity was 67 (36) cm/s with atrial contraction and 80 (25) cm/s with ventricular contraction. The atrial contribution to total pulmonary blood flow in patients with tricuspid atresia was significantly higher (53 (11)%) than in those with double inlet left ventricle (37 (14)%). Pulmonary artery flow after modified Fontan operation was biphasic and was related to both atrial and ventricular contraction. The atrial contribution to pulmonary blood flow is greater in patients with tricuspid atresia than in those with a double inlet left ventricle. The mechanism of the second peak related to ventricular contraction is unknown. PMID- 2223307 TI - Primary balloon dilatation of coarctation of the aorta in neonates. AB - Primary balloon dilatation of coarctation of the aorta was attempted in 10 consecutive neonates (age range 2-23 days). The coarctation site was crossed and the balloon inflated in all but one patient. In two patients with associated severe isthmal hypoplasia there was no change in the gradient after dilatation. In the remainder, the residual gradients were trivial and angiography showed complete relief of coarctation. Severe recoarctation developed 5-12 weeks after dilatation in five patients, each considered to have had an excellent initial result. The coarctation was rapidly progressive in three patients in whom Doppler studies within two weeks of the development of recoarctation had shown no significant gradient. In the other two patients progressive restenosis was charted by Doppler examinations over the course of 6-8 weeks. Three patients had a second, initially successful, dilatation procedure. One patient remained well with no residual gradient 18 weeks later. Stenosis recurred within eight weeks in the other two, and both have undergone successful surgical repair. Balloon dilatation of a native coarctation of the aorta gave excellent immediate results in most neonates. Severe isthmal hypoplasia is, however, a contraindication to balloon dilatation and early restenosis is an important problem. These results do not support the continued use of primary balloon dilatation of coarctation of the aorta in neonates. PMID- 2223308 TI - Transoesophageal echocardiography in the longitudinal axis: correlation between anatomy and images and its clinical implications. AB - Transoesophageal echocardiographic imaging in the longitudinal axis is a recent addition to the non-invasive evaluation of congenital and acquired heart disease. The technique provides unique images of intracardiac anatomy but their interpretation remains difficult. A heart specimen was therefore cut according to the echocardiographic imaging planes to elucidate the morphological details. The results suggested that longitudinal transoesophageal imaging complements the transverse axis approach. It gave new imaging information on the right ventricular outflow tract and the pulmonary trunk, the atrioventricular valves, the interventricular septum, the cardiac apex, and the thoracic aorta. In particular, it showed the entire length of the right ventricular outflow tract. When longitudinal imaging was used in combination with transverse imaging almost all the thoracic aorta could be examined. Imaging in the longitudinal axis may also allow better assessment of the mechanisms of atrioventricular valve regurgitation. PMID- 2223310 TI - Trauma. PMID- 2223309 TI - Rash after treatment with anistreplase. AB - A palpable purpura developed on the legs and lower abdomen of a woman of 54 five days after she was treated with anistreplase anisoylated plasminogen streptokinase activator complex (APSAC) for an acute myocardial infarction. Histological examination of a skin biopsy specimen taken 6 days after treatment showed leucocytoclastic vasculitis. The rash resolved within two weeks and there were no other complications. PMID- 2223311 TI - Trauma. PMID- 2223313 TI - The pathophysiology of multi-system organ failure in the trauma patient. AB - Multiple trauma mortality in the critical care setting most often occurs as a result of multi-system organ failure (MSOF). Mortality rates increase exponentially as successive organ systems fail. Although the role of shock in determining patient outcome has been extensively investigated, inflammatory factors and sepsis are becoming increasingly implicated in the development of MSOF. The physiologic effect of these factors on individual organ systems is explained. Signs, symptoms, and key criteria for determining organ system failure also are presented to assist the nurse in recognition and prevention. PMID- 2223314 TI - Clinical management of the pregnant trauma victim. AB - The pregnant trauma victim presents unique challenges to medical care providers because two lives must be treated concurrently. Physiologic changes inherent in the normal pregnancy, modify the assessment and treatment routines. Care directed to the mother impacts the fetus. Management of the pregnant trauma victim requires a high index of suspicion. Accurate assessment and timely interventions will enhance the probability of healthy outcomes for both mother and infant. PMID- 2223312 TI - Air transport of the trauma patient. AB - Flight nursing is a rapidly growing field in critical care nursing. An understanding of the types of trauma patients that warrant helicopter transport is important to any well functioning trauma system. The assessments and interventions necessary in transporting trauma patients are addressed. Safety, environmental, and psychosocial issues that surround the use of air transport are discussed. PMID- 2223315 TI - Caring for trauma victims: the emotional impact. AB - The potential for significant emotional trauma exists for nurses working with trauma victims and their families. There is very little in the nursing literature that addresses the wide range of normal feelings that nurses may experience during or following the care of trauma victims. There is also a scarcity of articles identifying strategies that nurses may employ to assist them through these significant incidents. This article describes the range of feelings that nurses may experience in the course of delivering care and relates these feelings to the traumatic event. Potential aggravating factors are discussed, and strategies are provided that nurses can use to survive the psychologic impact of these incidents and to achieve a higher level of emotional functioning. PMID- 2223316 TI - Physiologic response to traumatic shock. AB - Traumatic injury results in major physiologic alterations that begin at the time of injury and persist until recovery is complete. The response of the body is divided into two phases--the acute phase and the flow phase. The acute phase is characterized by shock with changes in hormone concentration. These hormones, either alone or in combination, result in lipolysis, amino acid release, gluconeogenesis,, and glycolysis. The flow phase of injury is a catabolic process that is characterized by an increased protein metabolism. Hypermetabolism and increased nitrogen losses are seen. The magnitude of these alterations is directly related to the severity of injury. Tissues with the highest oxygen consumption are more susceptible to injury and death. Cellular function does not depend on oxygen alone but also on the ability of the cells to use available oxygen. If the body is unable to compensate through biochemical, hormonal, and metabolic activities, an irreversible state results unless appropriate interventions are instituted promptly. PMID- 2223317 TI - Families experiencing a traumatic accident: implications and nursing management. AB - Families experiencing a traumatic accident experience significant psychosocial disruption. The traumatic event is sudden and unexpected. Families have no opportunity to prepare themselves emotionally, have limited experience with such catastrophic events, and are overwhelmed by the magnitude of the patient's injuries. Critical care nurses have an important role in the psychosocial assessment, support, and management of these families. Many critical care nurses are uncomfortable interacting with families with significant psychosocial/emotional needs due to a lack of understanding of their needs, lack of knowledge of how to manage their needs, lack of confidence in communicating with families, and generalized discomfort and awkwardness when confronted with grief and bereavement issues. This article presents important information for critical care nurses to help them understand and manage families psychosocial needs and to feel more confident interacting with these families. Information presented includes (1) impact of the traumatic event, (2) emotional responses, (3) assessment of psychosocial needs, and (4) nursing interventions for the care and management of these families. Special considerations impacting on families' psychosocial needs, including dysfunctional families, ineffective coping mechanisms, suicide, and the patient's death, are presented. PMID- 2223318 TI - Inhalation injuries. AB - Inhalation injuries comprise three distinct clinical entities that may be classified according to the time of onset of symptoms, etiologic agents, and the anatomic location of injury. These entities are carbon monoxide toxicity, upper airway obstruction, and smoke inhalation or chemical injury. Each has a distinct pathophysiology, clinical manifestations, treatment, and prognosis. The emergency management of inhalation injury is frequently based on the health professional's degree of suspicion despite the availability of sophisticated diagnostic tests. Early aggressive treatment, including maintaining a patent airway, administering humidified oxygen and bronchodilators, and providing pulmonary toilet, is necessary to ensure the best possible outcome. Understanding the pathophysiology, clinical manifestations, diagnosis, medical management, and nursing implications of inhalation injuries can improve patient survival. PMID- 2223319 TI - Wound care. PMID- 2223320 TI - Physiology of wound healing and risk factors that impede the healing process. AB - In the critically ill patient, wound repair can be impeded by processes inherent to the illness, its treatment, and the critical care environment. This vulnerability to wound complications increases patient morbidity and mortality as well as length of stay, resource consumption, and hospital cost. The physiology of wound healing and factors that impede wound repair are discussed. Those factors commonly seen in critical illness include advanced age, diabetes mellitus, compromised immunocompetence, inadequate perfusion, and oxygenation, infection, malnutrition, obesity, and preoperative illness. Knowledge of management of the physiologic factors that affect wound healing enables the nurse to maximize tissue repair and prevent wound complications. PMID- 2223322 TI - Choosing a wound dressing: a systematic approach. AB - Wound care presents a particular challenge in the critical care setting. Decisions about how to cleanse a wound and which dressing to use are often complicated by unexpected changes in the patient's condition, or the sudden occurrence of a wound infection. In this high-risk patient population, timely changes in topical therapy often can mean the difference between a wound that heals, or one that rapidly deteriorates. Much of the confusion over wound care and wound care products can be minimized by using a systematic approach to wound assessment. This chapter describes such an approach and summarizes local treatment options based on wound appearance. PMID- 2223321 TI - Human wound assessment: status report and implications for clinicians. AB - Wound care has long been carried out by professional nurses. Yet, as a result of their increasing qualifications and changes in health care practices, the nurse's role in and responsibility for wound care has expanded. Despite this, there is a paucity of valid and reliable methods by which nurses and physicians alike can evaluate healing status. This chapter provides an overview of the instruments designed to evaluate healing in humans, focusing particular attention on those intended to measure healing noninvasively. Implications for clinical practice and suggestions for research also are offered. Additionally, this article is written to raise clinicians' awareness to the need for concentrated efforts in devising clinically usable, valid, and reliable instruments to evaluate human tissue repair. PMID- 2223323 TI - The influence of tissue oxygen and perfusion on wound healing. AB - The availability of oxygen (O2) to cells in the wound area and the presence of adequate blood flow are important factors to the healing process. Oxygen plays a critical role in the formation of collagen, the growth of new capillaries, and the control of infection. Perfusion and delivery of O2 to tissue are closely related. Although an adequate blood flow does not guarantee a sufficient supply of O2, without it the provision of O2 to healing tissues will be impaired. Basic scientific studies have clarified how O2 and blood flow influence healing. Recent research has focused on clinical populations and begins to provide direction for additional clinical studies and interventions to support the healing process. Based on existing research, clinical interventions aimed to maintain perfusion and supply of O2 include fluid volume assessments, pulmonary hygiene regimens, postoperative position changes, and ambulation. PMID- 2223324 TI - Nutrition: a critical component of wound healing. AB - Nutrients are essential to wound healing and patients in critical care are often at risk for lack of sufficient nutrients that may result in impaired healing. Understanding the role of the various nutrients in healing provides the basis for assessment and therapy. Use of a practical and consistent nutritional assessment technique is an important part of care for critically ill patients with wounds. The health care team must provide care based on current knowledge of the effects of nutrition on wound healing and work collaboratively in doing nutritional assessment and providing nutritional support to optimize wound healing outcomes. PMID- 2223325 TI - Wound healing in the surgical patient: influence of the perioperative stress response on perfusion. AB - The clinical effect of surgical stress created by pain, cutting, cold, fear, and hypovolemia is peripheral vasoconstriction which limits wound perfusion and oxygenation and impairs wound healing. Correction of all factors as simultaneously as possible is the goal. PMID- 2223326 TI - Pressure ulcer prevention in critical care: state of the art. AB - Prevention of pressure ulcers in the critically ill patient is a major responsibility of the critical care nurse. The authors review the causes of pressure ulcer development and the methods of identifying the patient at increased risk. Pressure relief strategies for use in critical care are presented, and currently available pressure reduction and relief devices are discussed. Because few research studies address pressure ulcer prevention in the critical care setting, future research in this area is needed to develop a reliable predictive tool for use with the critically ill patient. Level of risk needs to be linked with intervention to assist the nurse in managing the pressure relief options available in today's market. In the meantime, prevention of pressure ulcers in critical care patients requires vigilance and the best use of available knowledge in the field. PMID- 2223327 TI - Studies on the expression of intracellular and surface polarity in animal pole cells of Xenopus embryos cultured on various substrata. AB - The expression of intracellular and surface polarity in animal pole cells of Xenopus embryos (stage 10) cultured on various substrata was studied by electron microscopy. When animal pole cells of Xenopus embryos were cultured on type I collagen- or gelatin-coated dishes until control embryos reached stage 23, the cells in confluent layers expressed an apical-basal polarity so that the apical surface membrane domain faced the culture medium. However, the cells in confluent layers cultured on naked plastic dishes were suppressed to express intracellular and surface polarity. In addition, single attached cells which were formed by being sparsely plated neither spread on any substrata nor displayed the apical basal polarity perpendicular to the dishes. These results indicate that the expression of intracellular and surface polarity in cultured animal pole cells of Xenopus embryos requires not only cell-cell contact but also an adhesive substrata such as type I collagen or gelatin. PMID- 2223328 TI - The process of new plasmalemma formation in focally injured skeletal muscle fibers. AB - The major ultrastructural events in murine skeletal muscle fibers were examined 3 to 24 hr after segmental injury induced by painting with aldehyde fixative. At 3 hr the viable stump of injured myofibers was separated from the necrotic segment by a zone of supercontracted myofibrils. No demarcating membrane was evident at this time, although occasionally collapsed segments of plasmalemma partially covered the viable stump. By 12 hr after injury myonuclei near the viable stump were centrally placed and numerous whorls of membrane material appeared in the vicinity of the Golgi apparatus. At this stage a convoluted, tortuous membrane exhibiting extensive interdigitations has sealed the structurally normal part of the injured fiber. The myoplasm immediately within this demarcating membrane possessed few myofilaments but numerous vesicles and tubules, several of which were continuous with the demarcating membrane; most degraded sarcoplasmic organelles remained external to the demarcating membrane and leukocytes were observed internalizing the debris. It appears that after segmental injury to skeletal muscle fibers, active production of new sarcoplasmic membranes occurs, which contributes to the formation of the part of the plasmalemma that demarcates the viable portion of the muscle fiber from the injured area. PMID- 2223329 TI - Characteristic views of Escherichia coli RNA polymerase core enzyme in the scanning transmission electron microscope. AB - Eight characteristic views of Escherichia coli RNA polymerase core enzyme are presented which were found using multivariate statistical image processing of about 1000 individual molecular images. The data set was obtained from negatively stained specimens with a scanning transmission electron microscope (STEM) operated in dark field mode. The molecular projections were found to a resolution of around 30 A, thus visualizing new structural details of the core enzyme. An approximate twofold axis seems to relate the beta to the beta' subunit as well as both alpha units to each other. PMID- 2223330 TI - Total i.v. anaesthesia with propofol and alfentanil: dose requirements for propofol and the effect of premedication with clonidine. AB - We determined in 51 healthy patients undergoing body surface surgery the dose requirements for propofol, as part of a total i.v. anaesthesia technique with an alfentanil infusion. After premedication with temazepam, patients received alfentanil 50 micrograms kg-1 followed by an infusion of 50 micrograms kg-1 h-1. Patients were anaesthetized with a loading dose of propofol followed by a three stage infusion designed to reach one of five preselected blood concentrations of propofol. The motor response to the initial surgical incision was noted and probit analysis was used to derive the ED50 (2.94 mg kg-1 h-1; 95% confidence limits: 2.35-3.37 mg kg-1 h-1) and ED95 (4.98 mg kg-1 h-1; 95% limits: 4.13-8.8 mg kg-1 h-1) for the final propotol infusion rate under these conditions. Whole blood concentration!of propofol at the time of the incision was related linearly to the inf!sion rate and the EC50 and EC95 (probit analysis) were derived as !.44 (95% confidence limits 0.62-1.87) and 4.05 (95% confidence lim!ts 2.78-30.5) micrograms ml-1, respectively. Post-operative recovery was!rapid, uncomplicated and uneventful. In a subgroup of eight patients,!the addition of clonidine 0.6 mg to the premedication significantly decreased the requirement for propofol (P less than 0.05) during surgery, but resulted in prolonged recovery times. PMID- 2223331 TI - Analgesic efficacy of i.m. alfentanil. AB - We have studied the analgesic, respiratory, cardiovascular and sedative effects of alfentanil 30 micrograms kg-1 i.m. in two experiments in six healthy volunteers. In the first experiment, recordings were made up to 120 min after injection. Thresholds (sensory and pain) and pain-related evoked potentials (amplitude and latency) to cutaneous argon laser stimulation were used for quantitative assessment of onset, efficacy and duration of analgesia. Pain was significantly reduced from 5 to 60 min after injection. The onset phase of analgesia was faster than the recovery phase. In the second experiment, the alfentanil-induced analgesia was antagonized by naloxone 0.4 mg i.v. The reaction time to pain was prolonged significantly 15 min after injection, whereas the latency of the pain-related potential remained constant. No clinically significant changes were observed in respiratory and cardiovascular measurements. PMID- 2223332 TI - Effect of surgery on sensory threshold and somatosensory evoked potentials after skin stimulation. AB - We have studied the effect of surgical injury on cutaneous sensitivity and somatosensory evoked potentials (SSEP) to dermatomal electrical stimulation in 10 patients undergoing hysterectomy. Forty-eight hours after surgery, sensory threshold increased from 2.2 (SEM 0.3) mA to 4.4 (1.1) mA (P less than 0.01) and SSEP amplitudes in P1, N1, P2 and the peak-to-peak amplitudes decreased (P less than 0.05). Latency was prolonged only in the N3 component (P less than 0.05). No changes were seen in threshold and SSEP in a control group studied over the same interval. The results suggest that surgical injury activates antinociceptive modulatory systems. PMID- 2223333 TI - Pharmacokinetics of propofol infusions in patients with cirrhosis. AB - We have compared the pharmacokinetics of propofol as an infusion in 10 control and 10 patients with cirrhosis. Anaesthesia was induced within 3-4 min during administration of an infusion of propofol 21 mg kg-1 h-1. After 5 min, the infusion was decreased in a stepwise manner to 12 mg kg-1 h-1 and subsequently 6 mg kg-1 h-1. The mean recovery time after discontinuation of the infusion was significantly longer in the cirrhotic group; however, when patients opened their eyes, blood concentrations of propofol were similar in both groups (1 micrograms ml-1). Pharmacokinetic analysis was performed from the beginning of infusion to 8 h after termination. Total body clearance was not reduced significantly in cirrhotic (1.56 (SD 0.48) litre min-1) compared with control (1.75 (0.32) litre min-1) patients. The volume of distribution at steady state was significantly greater in patients with cirrhosis than in control patients (202 (82) litre vs 121 (49) litre). However, this difference did not change terminal elimination half-life. The pharmacokinetics of propofol given by infusion to maintain general anaesthesia were not affected markedly by moderate cirrhosis. PMID- 2223334 TI - Effect of propofol on peripheral vascular resistance during cardiopulmonary bypass. AB - Twenty-eight patients undergoing elective coronary artery bypass surgery were allocated randomly to receive either propofol 2 mg kg-1 or an equivalent volume of its vehicle during cardiopulmonary bypass with constant pump flow. Peripheral vascular resistance (PVR) was calculated from perfusion pressure and pump flow. After propofol, PVR decreased from 1767 (SD 415) dyn s cm-5 to a minimum of 1263 (283) dyn s cm-5 at 2 min, and remained significantly less than the control value until 12.5 min after administration of propofol. In the group given the vehicle, PVR did not change significantly. In a second study in 10 patients, venous blood samples were withdrawn before and 2, 4, 6, 8, 10, 20 and 30 min after injection of propofol 2 mg kg-1 during cardiopulmonary bypass, for measurement of blood concentrations of propofol. Concentrations were greater than predicted by a computer simulation based on published pharmacokinetic data. The decrease in PVR may be an important factor in the hypotension caused by propofol during induction of anaesthesia. PMID- 2223335 TI - Effect of flumazenil on midazolam-induced amnesia. AB - We have studied the effect of i.v. flumazenil 0.01 mg kg-1 on the amnesia and sedation caused by midazolam 2 mg and 5 mg i.v. in volunteers in order to determine the relationship between the actions of the antagonist on these two effects. Midazolam caused dose-dependent central neural depression as assessed by critical flicker fusion frequency, and dose-dependent amnesia for word cards. In subjects given flumazenil 5 min after administration of midazolam, fusion frequency readings and memory were restored to levels comparable to those before midazolam administration. These two effects of flumazenil were similar in time course and extent, suggesting that they share the same mechanism of action. Flumazenil given alone had no effect on memory. The study has demonstrated anterograde amnesia following benzodiazepine administration and antagonism by flumazenil. There was neither retrograde amnesia nor retrograde antagonism of amnesia. PMID- 2223336 TI - Measurement of entrainment ratio during high frequency jet ventilation. AB - We have measured tidal (VT), entrained (Ve) and "blowback" (Vbb) volumes during high frequency jet ventilation (HFJV) through a Mallinckrodt Hi-Lo Jet tracheal tube in anaesthetized patients. The above volumes were calculated by digital integration of the appropriate regions of flow curves derived from a pneumotachograph placed between the bias flow tubing and the tracheal tube. At a driving pressure of 1 bar, lung minute ventilation increased with increasing ventilatory frequency, whilst tidal volumes decreased. The contribution of entrainment to tidal volume (Ve/VT) remained constant, although the volumes entrained were relatively small and varied widely from subject to subject. Blowback volumes were considerable, especially at ventilatory frequencies used clinically (1-2 Hz). We conclude that it is not possible to entrain predictable concentrations of volatile agents from the low pressure bias flow during HFJV. PMID- 2223337 TI - Plasma concentrations of methadone during postoperative patient-controlled extradural analgesia. AB - Plasma concentrations of methadone were measured by gas chromatography in 16 patients receiving extradural methadone by continuous infusion for relief of postoperative pain. Venous blood samples were taken after a loading dose of extradural methadone 2 mg and during infusion of 0.46 mg h-1 plus patient controlled increments of 0.2-1 mg. Mean (SD) plasma concentration of methadone was 9.8 (2.1) ng ml-1 at 15 min; this did not change significantly during the first 2 h, after which it increased gradually to 32.2 (4.6) ng ml-1 (P less than 0.001) at the end of 24 h. The mean quantity of extradural methadone required to produce effective analgesia was 10.3 (1.8) mg during the first 12 h after operation and 6 (1.0) mg for the subsequent 12 h. The mean amount of methadone for effective analgesia on the second day was 7.6 (1.1) mg. No adverse effects were detected during the 2-3 days of methadone therapy. Plasma concentration of methadone increased significantly during patient-controlled infusion of extradural methadone in the first 24 h after operation, suggesting rapid vascular uptake. Systemic activity of the drug contributes to the analgesic effect of extradural methadone. PMID- 2223338 TI - Effects of nitrous oxide on cerebral metabolic rate in rats anaesthetized with isoflurane. AB - It has been demonstrated in several species that a significant increase in cerebral blood flow (CBF) occurs when nitrous oxide is added to a volatile anaesthetic. This blood flow response could result from an increase in cerebral metabolic rate or from a direct effect of nitrous oxide on cerebral vessels. To investigate this, the cerebral metabolic rate for glucose (CMRglu) was determined autoradiographically in rats receiving isoflurane anaesthesia with or without nitrous oxide. An increase in anaesthetic depth from 0.5 to 1.0 MAC achieved with isoflurane alone caused a significant reduction in CMRglu (52 (SD11) mumol/100 g min-1 vs 39 (8)mumol/100 g min-1). In contrast, the addition of 70% nitrous oxide (0.5 MAC) to 0.5 MAC isoflurane anaesthesia (1 MAC total) left CMRglu unchanged (54 (4) mumol/100 g min-1). We conclude that 70% nitrous oxide does not alter cerebral metabolic rate when administered with 0.5 MAC isoflurane. Because CBF increases substantially under very similar conditions, our data indicate that the CBF effects of nitrous oxide, when administered with a volatile agent, were direct and mediated by factors other than changes in cerebral metabolic rate. PMID- 2223339 TI - IV lignocaine fails to attenuate the cardiovascular response to laryngoscopy and tracheal intubation. AB - I.v. lignocaine has been used with varying success to attenuate the cardiovascular responses to laryngoscopy and tracheal intubation. We determined the optimal time of administration in 45 ASA I and II Chinese patients premedicated with morphine and hyoscine, and anaesthetized with thiopentone and suxamethonium. Patients were allocated randomly to a control group or three treatment groups to receive lignocaine 1.5 mg kg-1 i.v. 1, 2, or 3 min before laryngoscopy. Analysis of variance for measured and derived cardiovascular variables failed to show any significant difference between any of the groups. PMID- 2223340 TI - Dose-dependent effect of metoclopramide on cholinesterases and suxamethonium metabolism. AB - In obstetric patients undergoing postpartum tubal ligation, we found that metoclopramide produced dose-dependent prolongation of suxamethonium-induced neuromuscular block. Mean block times after suxamethonium 1 mg kg-1 were 8.0 min, 9.83 min and 12.45 min for control and metoclopramide 10 mg and metoclopramide 20 mg groups, respectively. A laboratory study was therefore conducted on the inhibition of human plasma cholinesterase (PCHE) and erythrocyte acetylcholinesterase (ACHE) activity by varying concentrations of metoclopramide using acetylthiocholine as substrate. PCHE showed a greater sensitivity to inhibition by metoclopramide; the concentration of metoclopramide producing 50% inhibition of activity (I50) was 3.16 x 10(-7) mol litre-1, which is within the therapeutic range. ACHE was less sensitive to inhibition by metoclopramide (I50 2.24 x 10(-5) mol litre-1). Analysis of enzyme kinetics at varying substrate concentrations revealed that metoclopramide produced a potent non-competitive, dose-dependent inhibition of both ACHE and PCHE. The inhibition constant, Ki, was 1.88 x 10(-7) mol litre-1 for PCHE and 9.5 x 10(-8) mol litre-1 for ACHE. As metoclopramide is a potent inhibitor of PCHE, interactions might be expected to occur between metoclopramide and drugs that require PCHE for biotransformation, such as suxamethonium and ester local anaesthetics. PMID- 2223341 TI - Extradural, spinal or combined block for obstetric surgical anaesthesia. PMID- 2223342 TI - Spinal anaesthesia with hypobaric 0.19% or plain 0.5% bupivacaine. AB - Hypobaric 0.19% bupivacaine (plain 0.5% bupivacaine 3 ml + distilled water 5 ml) was compared with 0.5% plain bupivacaine 3 ml for spinal anaesthesia in 29 healthy patients undergoing orthopaedic surgery of the lower extremities. The solutions were injected at the L3-4 interspace in 40 s, and patients were kept sitting for 2 min after injection. The mean maximal cephalad spread of sensory block was to the T1 segment (SD 3.6) and to T8 (4.1) in the hypobaric and plain bupivacaine groups, respectively (P less than 0.0001). The study was interrupted after observing the sensory block of the 29th patient (hypobaric bupivacaine) spread to C2 within 5 min of injection. In most patients, the hypobaric bupivacaine block affected the upper thoracic nerves, and in three patients the cervical nerves also. The high levels of block were accompanied by marked hypotension. The extensive spread of the blocks makes this hypobaric spinal anaesthesia technique unsuitable for routine use. PMID- 2223343 TI - Extradural anaesthesia in patients with previous lumbar spine surgery. AB - We studied prospectively 1381 patients undergoing extradural anaesthesia for total hip or total knee replacement, to determine if extradural anaesthesia can be performed reliably in patients who have had previous lumbar spine surgery. Fifty-two of the 57 patients (91.2%) who had undergone lumbar spine surgery received a successful extradural anaesthetic, and 1307 of 1324 patients without previous back surgery had successful extradural anaesthesia (98.7% success) (P less than 0.0001). No late complications were observed. Causes for failure of extradural anaesthesia in patients who had previously undergone lumbar spine surgery included technical difficulty (three) and inadequate spread (two). PMID- 2223344 TI - Double-blind comparison of topical lignocaine-prilocaine cream (EMLA) and lignocaine infiltration for arterial cannulation in adults. AB - In a double-blind, double-dummy study, the efficacy of topical 5% EMLA cream was compared with that of lignocaine infiltration in alleviating the pain of arterial cannulation. Forty unpremedicated adults were allocated randomly to four groups to receive EMLA cream alone, EMLA and 0.9% saline infiltration, EMLA and 1% lignocaine infiltration or placebo cream and 1% lignocaine infiltration. Following arterial cannulation, pain was assessed by the patient using a visual analogue score and by an independent observer using a four-category verbal rating score. Significantly lower pain scores were observed in all patients receiving EMLA compared with those receiving placebo cream and lignocaine infiltration by both patient (P less than 0.01) and observer (P less than 0.001) assessments. There were no significant differences between the three EMLA groups. PMID- 2223345 TI - Plasma concentrations of bupivacaine after stellate ganglion block using two volumes of 0.25% bupivacaine plain solution. AB - Plasma concentrations of bupivacaine were measured in patients after stellate ganglion block using either 10 or 20 ml of 0.25% plain solution. The mean peak concentrations were greater in the larger volume group, but this was not statistically significant. From 30 min after injection, there was a significantly greater plasma concentration in the larger volume group. The concentrations approached the limit of detection in the smaller volume group at 2 h after block. PMID- 2223346 TI - Comparison of four pulse oximeters: effects of venous occlusion and cold-induced peripheral vasoconstriction. AB - The ability of four pulse oximeters (the Ohmeda 3700, Nellcor N100 and N200 and the Datex Oscar) to detect hypoxaemia was determined in the presence of venous obstruction and cold-induced peripheral vasoconstriction. Significant increases in detection time for hypoxaemia were found in both cases. There were no significant differences in detection time between the instruments, although the Ohmeda 3700 displayed smaller values of SaO2 under certain conditions. Peripheral vasoconstriction was induced using three differing methods which gave differing results, thus emphasizing the importance of methodology in assessments of pulse oximetry. PMID- 2223347 TI - Critical volume for pulmonary acid aspiration: reappraisal in a primate model. AB - We have studied, in the monkey, the critical volume for the production of severe pneumonitis following pulmonary aspiration of gastric contents. Aspiration of 0.4 ml kg-1 and 0.6 ml kg-1 at pH1 produced mild to moderate clinical and radiological changes, but no deaths. Aspiration of 0.8 ml kg-1 and 1.0 ml kg-1 at pH1 was associated with an increasingly severe pneumonitis. At 1.0 ml kg-1, 50% of the animals died--a mortality rate considerably less than that reported previously in animal studies. If these results were to be extrapolated to humans, the critical volume for severe aspiration could be increased from 25 ml to 50 ml (0.8 ml kg-1), considerably reducing the percentage of patients perceived to be "at risk". PMID- 2223348 TI - Site of action of fentanyl in inhibiting the pituitary-adrenal response to surgery in man. AB - To determine the site of action of fentanyl in attenuating the pituitary-adrenal response to surgery, we have measured serum concentrations of cortisol and growth hormone during and after a standardized surgical procedure in two groups of patients. One group received fentanyl 15 micrograms kg-1 i.v. immediately before the start of surgery; a second group received fentanyl 15 micrograms kg-1 i.v. together with corticotrophin releasing factor 100 micrograms i.v., growth hormone releasing hormone 100 micrograms i.v. and arginine vasopressin 10 units i.m. The concomitant administration of the releasing factors with the opioid resulted in a significantly greater serum concentration of cortisol 30, 60, 120 and 240 min after surgery commenced, compared with the group which received fentanyl alone. Similarly, the growth hormone response in the combined group was significantly greater than in the fentanyl-alone group 30 min after the start of surgery. We conclude that the inhibitory effect of fentanyl on surgically-induced secretion of pituitary hormone was mediated directly or indirectly via the hypothalamus. PMID- 2223350 TI - Rapidity and accuracy of tracheal intubation in a mannequin: comparison of the fibreoptic with the Bullard laryngoscope. AB - Successful tracheal intubation with the flexible fibreoptic bronchoscope requires a certain amount of skill which is acquired by practice. It has been suggested that the new Bullard laryngoscope may be mastered more easily. To determine if learning was superior with a flexible fibreoptic or the Bullard device, the ease of tracheal intubation with both devices was compared by first-year anaesthetic residents, using a mannequin modified to make intubation difficult. The Bullard laryngoscope was as easy to master as the flexible fibreoptic device, but passage of the tracheal tube took longer. Both devices require a similar amount of practice. PMID- 2223349 TI - Anaesthetic management of systemic mastocytosis. AB - Systemic mastocytosis is an uncommon disorder of mast cell proliferation in connective tissues. Mast cell degranulation may occur on exposure to various stimuli and drugs. The release of histamine, heparin and vasoactive substances such as prostaglandin D2 may cause severe hypotension and other anaphylactoid manifestations. Anaesthetic management should include perioperative stabilization of mast cells and avoidance of the use of histamine-releasing drugs. Intradermal skin testing is useful in predicting the sensitivity to drugs that may be used during anaesthesia. We present a patient with systemic mastocytosis who underwent uneventful cholecystectomy. PMID- 2223351 TI - Proceedings of the Anaesthetic Research Society. Southhampton, April 6-7, 1990. Abstracts. PMID- 2223352 TI - Subcutaneous flumazenil and recovery from midazolam. PMID- 2223353 TI - Organophosphorus insecticide poisoning. PMID- 2223354 TI - Blind nasal intubation--the only option. PMID- 2223355 TI - Spinal obstetric anesthesia with a 29-gauge needle. PMID- 2223356 TI - EMLA: complications. PMID- 2223357 TI - The Animals (Scientific Procedures) Act 1986 and research into anaesthesia. PMID- 2223358 TI - Quantitative EEG and brainstem auditory evoked potentials: comparison of isoflurane with halothane using the cerebral function analysing monitor. AB - We studied EEG and brainstem auditory evoked potentials (BAEP) during routine surgery at various concentrations of isoflurane (12 patients) or halothane (11 patients) or during prolonged (mean 2.5 h, range 1.9-3.5 h) administration of 1% isoflurane (five patients). Recording and analysis was performed with the cerebral function analysing monitor (CFAM). At equivalent MAC, the two agents exhibited distinctive neurophysiological profiles. Increasing concentrations of isoflurane produced a clear sequence of EEG changes (decreasing fast and increasing slow components) then burst suppression activity suggesting cortical depression. With halothane, changes in EEG amplitude were less pronounced and those in frequency content less systematic, with no periods of suppression. Simultaneous BAEP showed greater latency increase with halothane than with isoflurane. Prolonged administration of 1% isoflurane was associated with a stable EEG (no periods of suppression) and BAEP. PMID- 2223359 TI - Isoflurane prevents EEG depression during trimetaphan-induced hypotension in man. AB - We have studied the EEG analysed with the cerebral function analysing monitor (CFAM) during trimetaphan (TMP)-induced hypotension to a mean arterial pressure (MAP) of 40 mm Hg in 20 normocapnic patients anaesthetized with either 1% end tidal isoflurane or 0.5% halothane. During the acute reduction in MAP, the average reduction in mean EEG amplitude with halothane was 14%, two patients showing short periods of EEG suppression; the decline in EEG amplitude correlated with declining MAP in four patients. In contrast, the average reduction in mean EEG amplitude with isoflurane was only 0.3% and there were neither periods of suppression nor any correlation between EEG amplitude and MAP. No significant changes in EEG frequency occurred in either group. Isoflurane prevented EEG amplitude depression during TMP-induced hypotension. PMID- 2223360 TI - Lower oesophageal contractility and detection of awareness during anaesthesia. AB - We have investigated the value of lower oesophageal contractility (LOC) in detecting awareness during anaesthesia in 20 human volunteer patients. LOC was measured either with subjects awake or after induction with propofol, during induction with propofol, and then as consciousness returned. Statistically significant changes were observed in the frequency of spontaneous contractions, peak and mean amplitude of spontaneous and provoked contractions, and the oesophageal contractility index as subjects lost consciousness and also as it was regained. The differences in LOC which occurred when subjects were conscious and unconscious support the view that LOC is related to the depth of anaesthesia, but its unreliability at the interface between consciousness and unconsciousness prevents selective detection of awareness, although the response in the presence of painful stimuli has not been tested. PMID- 2223361 TI - Extradural methadone and bupivacaine in labour. AB - We performed a double-blind placebo-controlled study of the effects of extradural administration of methadone 5 mg or saline, followed by bupivacaine, in 42 women in early labour. Motor block and pain scores were significantly less in the methadone group. The requirement for bupivacaine also was reduced by methadone, but this was not statistically significant. There were no troublesome side effects attributable to methadone. PMID- 2223362 TI - Plasma concentrations of the stereoisomers of prilocaine after administration of the racemate: implications for toxicity? AB - A chiral high pressure liquid chromatography method was developed to measure the separate isomers of prilocaine in plasma after administration of the racemate. The concentrations of the isomers in six patients were similar (S(+)/R(-) = 1.06 (SD 0.06)) after brachial plexus block with 1.5% (RS)-prilocaine hydrochloride 35 ml, suggesting that a higher systemic safety margin may not be achieved by substituting racemic prilocaine by one of its isomers. Much higher plasma concentrations of the S(+)- than the R(-)-form after oral administration of 300 mg of the racemate (n = 4) indicated a large difference in intrinsic metabolic clearance of the isomers on first pass through gut, liver or both organs. PMID- 2223363 TI - Effect of different rates of infusion of propofol for induction of anaesthesia in elderly patients. AB - The effect of changing the rate of infusion of propofol for induction of anaesthesia was studied in 60 elderly patients. Propofol was administered at 300, 600 or 1200 ml h-1 until loss of consciousness (as judged by loss of verbal contact with the patient) had been achieved. The duration of induction was significantly longer (P less than 0.001) with the slower infusion rates (104, 68 and 51 s), but the total dose used was significantly less (P less than 0.001) in these patients (1.2, 1.6 and 2.5 mg kg-1, respectively). The decrease in systolic and diastolic arterial pressure was significantly less in the 300-ml h-1 group at the end of induction and immediately after induction (P less than 0.01). The incidence of apnoea was also significantly less in the slower infusion group. PMID- 2223364 TI - Cardiovascular effects of propofol and of thiopentone anaesthesia in the sheep. AB - We have examined the effects on the cardiovascular system and on regional blood flow of propofol and thiopentone when administered with IPPV (FIO2 0.4). A longitudinal study design was used in which 16 studies were performed in eight sheep for 30 min before, during the last 30 min of 70 min anaesthesia, and for 6 h after anaesthesia. During anaesthesia with propofol and thiopentone, mean total body oxygen consumption decreased, respectively, by 47% (P less than 0.001) and 24% (P less than 0.01) of pre-anaesthesia baseline values, mean heart rate increased by approximately 50% (P less than 0.05) with both agents, mean arterial pressures increased by approximately 50% (P less than 0.05) with both agents and the mean cardiac output was unaltered with propofol anaesthesia but was decreased by 20% (P less than 0.05) with thiopentone anaesthesia. The changes in arterial pressure and heart rate were unexpected and may have been a result of a species specific effect. Mean hepatic blood flow decreased consistently by a mean of 17% (P less than 0.01) during propofol anaesthesia, and inconsistently during thiopentone anaesthesia so that it was not significantly different from baseline values. Mean renal blood flow decreased during propofol anaesthesia by 7% (P less than 0.05) and by 27% (P less than 0.001) during thiopentone anaesthesia. Whereas most variables returned to baseline values within 2 h after propofol anaesthesia, this took 5 h after thiopentone anaesthesia. PMID- 2223365 TI - Effects of propofol and of thiopentone anaesthesia on the renal clearance of cefoxitin in the sheep. AB - We have examined the renal extraction ratios and clearances of cefoxitin in three groups of adult merino ewes. One group (n = 3) was studied for 12 h without perturbation; these were designated control studies. The other two groups (n = 4 each) were studied before (baseline values), during and after the induction and 70-min maintenance of anaesthesia with propofol or thiopentone. In the control studies, mean renal extraction ratio and clearance for cefoxitin were, respectively, 0.67-0.92 and 0.66-0.91 litre min-1 and were consistent throughout the entire study period in individual animals. Comparable values were obtained as baseline values in the anaesthesia groups. Compared with individual baseline values, blood concentrations of cefoxitin doubled during anaesthesia with each agent. At the same time, renal extraction ratio and clearance for cefoxitin each decreased significantly to about 50-60% of their control values. Recovery to control values of arterial blood concentrations and renal extraction ratio of cefoxitin took at least 5 h, but recovery of renal clearance was more rapid. The results indicate that renal elimination of an organic anion such as cefoxitin may be affected by changes in renal blood flow and in renal function produced by propofol and thiopentone; these effects may last for several hours after recovery of renal blood flow. PMID- 2223366 TI - Effects of propofol and of thiopentone anaesthesia on the regional kinetics of pethidine in the sheep. AB - We have examined the extraction ratios, net fluxes and clearances of pethidine by the liver, kidneys and hindquarters in sheep before, during and after continuous anaesthesia (70 min) with propofol or thiopentone. Before anaesthesia, the overall mean respective regional pethidine extraction ratios were 0.98 (SD 0.01), 0.20 (0.06) and 0.44 (0.13), the corresponding net fluxes were 47 (7), 5 (2) and 20 (10)% dose min-1 and the clearances 1.44 (0.22), 0.17 (0.07) and 0.80 (0.39) litre min-1. During propofol anaesthesia, arterial blood concentrations of pethidine approximately doubled (P less than 0.05), mean pethidine hepatic extraction ratio was unchanged, flux was increased to 145 (20)% and clearance decreased to 79 (10)% (P less than 0.05) of baseline values; mean pethidine renal extraction ratio, flux and clearance were 73 (34), 112 (43) and 69 (31)% of baseline values; mean hindquarter pethidine extraction ratio decreased to 65 (25)% (P less than 0.05) of baseline values. During thiopentone anaesthesia, arterial blood concentrations of pethidine approximately doubled (P less than 0.01), mean pethidine hepatic extraction ratio was 97 (2)% of baseline values and flux and clearance were unchanged, mean pethidine renal extraction ratios, flux and clearance decreased to 37 (21), 54 (18) and 27 (19)% (all P less than 0.05) of baseline values and mean pethidine hindquarter extraction ratio was 81 (20)% of baseline values. In spite of only modest changes in hepatic and renal blood flow during anaesthesia, blood concentrations of pethidine doubled and pethidine kinetics were disturbed for several hours after anaesthesia. Overall, however, the changes were of smaller magnitude and shorter duration than those that have been described for anaesthesia with the volatile anaesthetic agents. PMID- 2223367 TI - Effect of general anaesthesia on whole body protein turnover in patients undergoing elective surgery. AB - To determine if general anaesthesia alone or in conjunction with surgery alters body protein turnover, we studied six healthy, unpremedicated females undergoing elective total abdominal hysterectomy. Changes in protein metabolism, synthesis and breakdown were estimated by an isotope dilution technique using a continuous infusion of the stable isotope tracer, L-[1-13C]leucine, before anaesthesia (4 h), during anaesthesia alone (1 h), during anaesthesia and surgery (1 h) and in the recovery period (2 h). General anaesthesia comprised thiopentone, pancuronium, enflurane (1 MAC) and oxygen-enriched air. An isotopic steady state in plasma 13C-alpha-ketoisocaproate (13C alpha-KIC) and expired 13C-carbon dioxide were obtained during the four periods. Collections of plasma and expired air were made during the steady state periods and plasma alpha-KIC enrichment measured to indicate precursor pool labelling from which leucine flux (equal to protein breakdown in the post-absorptive state) and oxidation were calculated, and whole body protein synthesis was derived. Whole body protein breakdown did not change with anaesthesia, but decreased with both surgery and during the acute recovery period (P less than 0.05). Protein synthesis did not change with anaesthesia and surgery, but decreased significantly after surgery (P less than 0.05). PMID- 2223368 TI - Cerebral effects of sevoflurane in the dog: comparison with isoflurane and enflurane. AB - The cerebral effects of sevoflurane were compared in dogs with those of enflurane and isoflurane. Initially, the minimum alveolar concentrations (MAC) of sevoflurane and enflurane were determined and the electroencephalographic (EEG) responses to increasing doses of sevoflurane (1.5, 2.0 and 2.5 MAC) or enflurane (1.5 and 2.0 MAC) in unparalysed animals were examined. Administration of sevoflurane was not associated with seizure activity at any concentration either during normocapnia (PaCO2 5.3 kPa) or hypocapnia (PaCO2 2.7 kPa), even in the presence of intense auditory stimuli. All dogs anaesthetized with enflurane demonstrated sustained EEG and motor evidence of seizure activity induced by auditory stimuli at concentrations of enflurane greater than 1 MAC, particularly during hypocapnia. In a separate group of dogs, the effects of increasing concentrations of sevoflurane and isoflurane (0.5, 1.5 and 2.15 MAC) were compared directly on arterial pressure, cardiac output and heart rate, cerebral blood flow and the cerebral metabolic rate for oxygen (CMRO2) using the venous outflow technique. Sevoflurane, in common with isoflurane, had minimal effects on cerebral blood flow at the concentrations studied, but significantly reduced the CMRO2 at end-tidal concentrations sufficient to produce a burst suppression pattern on the EEG (approximately 2.15 MAC). Both sevoflurane and isoflurane significantly decreased arterial pressure in a dose-dependent manner, but neither drug significantly altered cardiac output. PMID- 2223369 TI - Failed tracheal intubation. PMID- 2223370 TI - Pupillary effects of alfentanil and morphine. AB - We have measured the onset and extent of the miotic effect of morphine and alfentanil in conscious patients. Forty unpremedicated ASA I and II patients were allocated randomly to four groups to receive either i.v. saline (control group), morphine 0.1 mg kg-1, alfentanil 4.0 micrograms kg-1 or a combination of these doses, and pupil diameters were measured for the next 30 min. There were no significant differences in the control diameters. In the opioid groups, a significant decrease in diameter (about 1 mm), occurred 4 min after administration of the drug and persisted throughout the study. The opioid groups behaved similarly for 25 min. After 10 min the mean diameter of the alfentanil group began to increase, but this did not reach statistical significance until after 25 min. PMID- 2223371 TI - Muscle relaxation rates in individuals susceptible to malignant hyperthermia. AB - Muscle relaxation rate following a tetanic stimulus of adductor pollicis muscle was measured prospectively in 26 patients potentially susceptible to malignant hyperthermia (MH) the day before a muscle biopsy was obtained for MH in vitro screening. Eleven subjects were found to be MH susceptible (MHS) and 15 subjects MH-negative (MHN). In all patients, relaxation rate was recorded at three different temperatures of the skin overlying adductor pollicis (30, 34 and 38 degrees C) achieved by a small surface heating unit placed over the thenar eminence. The MHS group exhibited slightly higher relaxation rate at 34 and 38 degrees C compared with the MHN group and this difference was accentuated with increasing temperature, but was not statistically different. The results of the present study suggest that relaxation rates are normal in MHS individuals under physiological conditions and cannot be used diagnostically for MH screening. PMID- 2223372 TI - Pivoting larynx--an unusual clinical observation at laryngoscopy. AB - Rigid oesophagoscopy was planned in the investigation of a young patient with dysphagia. During laryngoscopy for tracheal intubation an unusual pivoting manoeuvre was required to see the vocal cords. Although the initial diagnostic investigations were unhelpful, follow up directed at explaining the clinical observations led to an eventual diagnosis of anterior tubercles of C6, which explained the observation and accounted for the dysphagia. PMID- 2223373 TI - Prolonged paralysis following suxamethonium and the use of neostigmine. AB - A case of prolonged neuromuscular block following the administration of suxamethonium is reported. Three hours after administration of suxamethonium, a well defined, recovering phase II block was demonstrated with a T4:T1 ratio of 0.25, and neostigmine was administered. Although the T4:T1 ratio was improved to 0.9, T1 remained at 25% of control, and significant paralysis persisted which responded to administration of cholinesterase. It is concluded that neuromuscular monitoring cannot reliably predict reversibility in such cases and that, even after 3 h, antagonism of prolonged suxamethonium block should commence with cholinesterase, followed by neostigmine if necessary. PMID- 2223374 TI - Foam cuffed tracheal tubes: clinical and laboratory assessment. AB - The efficiency of a foam cuffed tracheal tube has been studied in protecting the pulmonary tree from aspiration of oropharyngeal and gastric contents. Following instillation of methylene blue dye above the cuff, subsequent fibreoptic bronchoscopy revealed no instance of dye staining of the tracheal mucosa. A "bench" study was undertaken subsequently to estimate the likely pressure that the cuff would exert on the tracheal mucosa as a result of elastic recoil properties of the foam. The results suggested that, under normal clinical conditions, the pressure is not likely to exceed a value at which impairment of the mucosal blood supply would occur. PMID- 2223375 TI - Axillary brachial plexus block: choice of technique? PMID- 2223376 TI - Body temperature and anaesthesia. PMID- 2223377 TI - Postoperative patient-controlled analgesia. PMID- 2223378 TI - The influence of age on N-isopropyl-p-[123I]iodoamphetamine accumulation in the human heart. AB - Variations in heart intensity in the 30 min and 4 hr chest images of the radiolabelled lipophilic amine, N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) were observed in 130 patients with lung diseases, aged 23 to 85 yrs. The heart intensity had a significant positive linear correlation with age (r = 0.43 at 30 min, 0.66 at 4 hr). The ratio of 4 hr heart intensity to 30 min heart intensity also had a positive linear correlation (r = 0.59), suggesting slower clearance of the radioactivity from the heart in older than in younger patients during this interval. Other parameters including sex, EKG findings, liver function, blood pressure, the presence of diabetes mellitus and smoking history had no relationship to heart intensity. A significant difference between heart intensities in bronchogenic carcinoma and pneumonia patient groups might be probably due to the age difference between the two groups. Therefore heart intensity in the 4 hr 123I-IMP image may reflect certain metabolic and/or myocardial change(s) with aging. PMID- 2223379 TI - Bone scanning in patients with pleural effusion--experience in 76 cases. AB - Seventy-six patients with malignant or benign pleural effusion were studied to determine the incidence of accumulation of 99mTc-MDP in relation to effusion, and reveal the mechanism. Of 76 patients, 46 (61%) were found to have diffuse uptake of 99mTc-MDP in the hemithorax, with almost the same positive rate in malignant and benign effusions, i.e. 62% and 57%, respectively. Of 46 patients, 32 (70%) showed diffuse, slight accumulation in the hemithorax, and the positive rate had a tendency to be higher with the increase in the effusion volume. We are convinced that the major mechanism of unilateral intrathoracic accumulation of 99mTc-MDP in pleural effusion is a passive transudation. PMID- 2223382 TI - Topographic EEG study of visual display terminal (VDT) performance with special reference to frontal midline theta waves. AB - Operators of visual display terminals (VDT) often complain of physical, as well as psychological stress. Under certain circumstances, increased psychological stress among VDT operators is seen to create serious problems in their occupations, yet few studies have dealt directly with this problem. It is not clear how this should be measured and evaluated. We report the results of experiments where psychological stress was induced during VDT tasks such as visual search and computer mouse operations. The relationship between spatio temporal analysis of EEG activity and productivity of VDT work was investigated. The subjects were divided into three age groups: young adults (18-22 years old), middle-aged (38-42 years old) and the elderly (58 years and over). Characteristic EEG changes occurred during VDT tasks. These consisted of frontal midline theta waves with maximum amplitude at Fz. Statistically significant relationships were found between duration of working, EEG electrode location on the head, as well as correlations between work speed and variation of theta waves. It was concluded that some factors relating to the severity of a mental task and the distribution of cortical EEG potentials are closely related. When long lasting theta waves appear in the EEG, a rest period should be considered, before the subjects complain of fatigue. An effective method to optimally determine the duration of work and rest periods can be designed using the EEG. PMID- 2223380 TI - Evaluation of viral myocarditis in children by radionuclide method. AB - Evaluation of viral myocarditis is essential for the clinician to assess the prognosis. In this study, Tl-201 myocardial scintigraphy and Tc-99m gated cardiac blood pool scan were performed in 16 patients with myocarditis diagnosed by clinical symptoms and laboratory findings and these nuclear medicine techniques were followed up for 5 years. Exercise Tl-201 scintigraphy using a bicycle ergometer was performed in 8 patients by SPECT imaging. There were mild to severe persistent defects found in all cases (100%), but pressure rate products showed normal response. The Tl-201 defect ratio improved gradually, but did not change significantly. In the resting Tl-201 image one of 16 patients showed severe multifocal defects. LVEF increased significantly from 1 year to 5 years after onset, while RVEF measured by gated blood pool scans showed slight increases 3 years to 5 years after diagnosis. It was concluded that myocardial perfusion improved only incompletely. Cardiac function (LVEF and RVEF) improved gradually, and pressure rate products were normal. Myocarditis should therefore be followed up in order to assess the prognosis; moreover, the relationship of myocarditis to dilated cardiomyopathy needs to be further studied. PMID- 2223381 TI - Radioimmunoscintigraphy of human pancreatic carcinoma xenografts in nude mice with 131I-labeled monoclonal antibody. AB - Encouraged by reports of radioimmunoimaging of colorectal carcinomas and by examining an immunohistochemical report on resected pancreas cancer tissues, we studied the diagnostic potential of radioimmunoimaging with the radioiodinelabeled monoclonal antibody to the surface antigen of a pancreas cancer cell line. A monoclonal antibody (MoAb; HC-1) to a human pancreas cancer cell line (HGC25)5 was labeled with radioiodine and injected into athymic nude mice implanted with human pancreas cancer cells. Antibody HC-1 was cleared from the circulation and accumulated significantly in the implanted tumor sites. PMID- 2223383 TI - A topographic study of differences in the P300 between introverts and extraverts. AB - This paper presents results of a study to establish a link between neurocognitive psychophysiological and psychological type data through the investigation of differences in topographic auditory event-related potential (AERP) (P300) patterns in strongly introverted (n = 17) and strongly extraverted ( = 16) high school males as identified by the Myers Briggs Type Indicator. Group data files were created for the auditory event related potential task and converted to ASCII form. Amplitude values were evaluated at each scalp site. Kruskal Wallis one way analysis of variance was performed to evaluate group differences. In processing of infrequent, target stimuli, the amplitude of the P300 waveform for introverts was higher than for extraverts. When processing for non-target stimuli was subtracted from target stimuli, statistical differences were found over nine central, parietal, and occipital sites. The findings support and extend theories of biologically-based and bio-psycho-social typology. PMID- 2223384 TI - Spatial patterns underlying population differences in the background EEG. AB - A method is described which can be used to extract common spatial patterns underlying the EEGs from two human populations. These spatial patterns account, in the least-squares sense, maximally for the variance in the EEGs from one population and minimally for the variance in the other population and therefore would seem to be optimal for quantitatively discriminating between the individual EEGs in the two populations. By using this method, it is suggested that the problems associated with the more common approach to discriminating EEGs, significance probability mapping, can be avoided. The method is tested using EEGs from a population of normal subjects and using the EEGs from a population of patients with neurologic disorders. The results in most cases are excellent and the misclassification which occurs in some cases is attributed to the nonhomogeneity of the patient population particularly. The advantages of the method for feature selection, for automatically classifying the clinical EEG, and with respect to the reference-free nature of the selected features are discussed. PMID- 2223385 TI - Comparison of conventional P3 determination with global field power in epilepsy patients. AB - The usefulness of global field power (GFP) determinations in assessing the cognitive event-related potential latency to an auditory "odd-ball" discrimination paradigm was explored in thirty epileptic patients. Relationships to measurements of intellectual and neuropsychologic test parameters were compared between conventional peak determinations and those obtained by GFP. Latencies as determined by GFP showed a greater number and more consistent relationships with neuropsychologic test measures than those obtained by conventional peak determinations. In some instances, GFP gave however also ambiguous results and the method cannot be substituted for conventional peak determinations, but must be used in conjunction in order to avoid spurious results. PMID- 2223386 TI - Advanced workshop on topographic EEG. Valle d'Aosta, Italy, September 7-10, 1989. Abstracts. PMID- 2223387 TI - Transforming collaborations between ras and nuclear oncogenes. AB - Nuclear proteins encoded by both cellular oncogenes and DNA tumor viruses enable activated ras oncogenes to transform a variety of cell types to a tumorigenic state. The interactions are complementary, suggesting that collaborating oncogenes release cells from controls that preclude transformation by ras alone. The nuclear oncoproteins bind both protein and nucleic acid targets and affect processes important in transcription and cell cycle control. Transforming collaborations between oncogenes provide a genetic context to study biochemical interactions involved in normal growth control and to identify mechanisms important in multistep carcinogenesis. PMID- 2223389 TI - Activation of programmed cell death by anticancer agents: cisplatin as a model system. AB - The anticancer drug cisplatin exerts its action as a consequence of interaction with DNA. Cell cycle progression facilitates sensitivity to the drug, but inhibition of DNA synthesis is not necessarily the critical step. Lethally damaged cells can progress to and arrest for several days in the G2 phase of the cell cycle before dying. Certain features of cisplatin-induced cell death, such as chromatin condensation and the activation of a DNA endonuclease, are reminiscent of apoptosis, or programmed cell death. Many other anticancer drugs produce the same phenotypic effects, suggesting that these agents may all interact with the same signal transduction pathway leading to cell death. PMID- 2223388 TI - The pS2 gene, mRNA, and protein: a potential marker for human breast cancer. AB - Approximately 50% of human breast tumors secrete a small cysteine-rich protein called pS2. In the human breast cancer cell line MCF-7, expression of the pS2 protein is strongly induced by estrogen, and cloning and sequence analysis of the pS2 gene has revealed an "estrogen responsive element" in the gene's 5'-flanking region. The results of immunohistochemical assays and radioimmunoassays on breast cancer biopsies indicate that the pS2 protein is a marker for hormone-dependent breast tumors and that its expression is associated with longer overall, and disease-free, survival. The pS2 protein is also expressed in normal stomach mucosa and in regenerative tissues in ulcerative diseases of the gastrointestinal tract. Its physiological function is unknown. PMID- 2223390 TI - Transforming properties of the HTLV-I tax gene. PMID- 2223391 TI - Murine models for human chronic myelogenous leukemia. PMID- 2223392 TI - Antimetabolites. PMID- 2223393 TI - New anticancer agents. PMID- 2223394 TI - Monoclonal antibody therapy of cancer. PMID- 2223395 TI - Adoptive cellular therapy. PMID- 2223396 TI - Alkylating agents. PMID- 2223398 TI - Leukemias and myeloma. PMID- 2223397 TI - Clinical use of differentiating agents in cancer therapy. AB - Conceptually, the use of cytodifferentiation agents to suppress oncogenicity may prove most effective in long-term continuous treatment of patients whose tumors display some inherent expression of differentiated characteristics. This is the case in many pre-malignant lesions. The difficulty in evaluating the therapeutic role for HMBA, the retinoids, and cytosine arabinoside is oftentimes in separating in vivo cytotoxic from cytodifferentiation effects. Only with further studies will it be determined whether these and other cytodifferentiation agents are therapeutically useful and whether they can provide additional understanding of the processes of cellular transformation and differentiation with which they interact. PMID- 2223399 TI - Lymphomas. PMID- 2223400 TI - Treatment of acquired immunodeficiency syndrome. PMID- 2223401 TI - Head and neck cancer. PMID- 2223403 TI - Upper gastrointestinal tumors. PMID- 2223402 TI - Anthracyclines. AB - After twenty years, understanding the mechanisms of tumor cells kill by anthracyclines still remains an active area of research. Of many mechanisms described for this class of drugs, efforts in the last year have focused on defining the role of free radical formation, topoisomerase II-induced DNA breakage, and P-170-dependent cellular accumulation of anthracyclines in tumor cell kill and resistance. First, in a number of tumor cell lines, the formation of free radical species from anthracyclines has been implicated in the cell killing. Modulation of detoxification pathways in a drug-resistant cell line e.g depletion of GSH, a substrate for peroxidase and transferase, enhanced both the formation of oxy-radicals and adriamycin cytotoxicity. It should be noted, however, that these findings are not true for every cell line examined, and free radical-mediated tumor kill may be cell- or tissue-specific. Second, anthracyclines-mediated topo II-dependent DNA cleavage was observed in most cell lines and reduced breaks were found in resistant cells. The decrease in single strand breaks, however, neither correlated with the degree of resistance nor with differences in the relative topo II activity, which was in most cases only two fold less in resistant cells than in sensitive cells. Finally, the reduced accumulation of the drug does not appear to be the only contributing factor in multidrug resistant cells and P-170 is not the only protein overexpressed in certain cells, e.g., an 85,000 Da protein may also be linked to adriamycin resistance. Although GST protein is overexpressed in most adriamycin resistant cells along with mdr1 gene, current evidence suggests that this protein may not be directly involved in adriamycin resistance. Taken together, both the mechanism of action and resistance to this class of drug likely vary among cell lines. Clinical studies in the past year have brought about interesting refinements in anthracycline-containing chemotherapy; ICRF-187 (by itself also cytotoxic) seems to offer protection against cardiac toxicity, while implicating iron in the mediation of cardiac damage. Out of a large number of newer anthracycline derivatives, clinical evidence indicates only a modest increase in therapeutic index with a few analogs, perhaps idarubicin and epirubicin. It is not yet clear that being able to receive more milligrams (or more cycles) of anthracycline eventually translates into a significantly better response rate or in a survival advantage. Much less clear is whether patients refractory to adriamycin may derive any benefit from newer anthracyclines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2223405 TI - Breast cancer. AB - Numerous important issues in breast cancer were debated this past year. Several examples include: the role of screening mammography in women aged 40-49, the management of carcinoma in situ, adjuvant chemotherapy for postmenopausal node positive women, adjuvant therapy for node-negative women, the primary management of elderly women with breast cancer, the use of a composite of prognostic factors for better predictive power and measures to improve the therapeutic index of the anthracyclines. PMID- 2223404 TI - Endocrine tumors. PMID- 2223406 TI - Malignant melanoma. AB - The papers reviewed in this chapter emphasise the continued difficulties in making progress with the management of advanced malignant melanoma. Data is consistently accrued to confirm the relatively favourable prognosis of thin lesions and hence the importance of early detection and educational programmes to help patients to seek medical assistance when early changes appear. The papers on regional perfusion show some encouraging results but for systemic metastases, cytotoxic drugs show very little if any true benefit. Conversely, the increased interest in biological response modifiers does hold out some genuine promise of being able to influence the course of this unpredictable and refractory malignant disease. PMID- 2223407 TI - Soft tissue and bone sarcomas. PMID- 2223408 TI - Brain tumors. PMID- 2223409 TI - Biological effects and clinical applications of human colony-stimulating factors. PMID- 2223410 TI - Podophyllotoxin derivatives. PMID- 2223411 TI - Cisplatin. PMID- 2223412 TI - A graphical presentation of the results of crossover trials. AB - 1. Crossover designs are widely used in clinical trials. A graphical method of describing the data as well as visually indicating the extent of treatment * period interaction and overall treatment effect is presented. This plots the treatment differences between the periods for each individual against the mean of their treatment outcomes. It is recommended that this plot accompany the analysis of crossover trials in order to aid summary and interpretation especially for the non-statistician. PMID- 2223413 TI - Assessment of quality of life in the treatment of hypertension. PMID- 2223414 TI - The measurement of quality of life in hypertensive patients: a practical approach. PMID- 2223415 TI - A comparison of verapamil and nifedipine on quality of life. AB - 1. Aspects of quality of life (symptoms, psychological well-being and activity) were evaluated by self-administered questionnaires in a 4 month randomised double blind trial of titrated doses of verapamil slow release (n = 41) compared with nifedipine retard (n = 40). An untreated diastolic blood pressure of 95-115 mm Hg was required for inclusion in the trial. 2. The mean age in both groups was 55 years. A significant difference between the two drugs was found in the average reporting of symptoms with an increase on nifedipine (P less than 0.01). The reporting of swollen ankles and flushing (P less than 0.05) increased on nifedipine, and nocturia (P less than 0.05) increased on verapamil. Measures of psychiatric morbidity tended to improve on verapamil and deteriorate on nifedipine. Only the change in cognitive function was significant between the drugs, being worse on nifedipine (P = 0.05). 3. There was no difference between the two groups in the fall in diastolic blood pressure (average 18 mm Hg on nifedipine and 17 mm Hg on verapamil). There was a significantly greater fall in systolic blood pressure on nifedipine (23 mm Hg) compared with verapamil (13 mm Hg) (P less than 0.01). 4. The two drugs differed in their effects on measures of quality of life. The improvements in symptomatic complaints and psychological well-being on verapamil may have been due to inclusion in a trial, although we cannot exclude the possibility of a drug effect. Conversely the increase in symptoms and self-assessed cognitive impairment on nifedipine were considered to be side-effects of the drug. PMID- 2223416 TI - Attenuation of the pupillary light reflex in anxious patients. AB - 1. The miotic responses evoked by brief light stimuli were compared between a group of 10 patients suffering from generalized anxiety disorder and 10 age- and sex-matched healthy control subjects. 2. Resting pupil diameter in the dark did not differ significantly between the two groups. 3. In both groups, the amplitude of the light reflex was linearly related to the logarithm of the intensity of the light stimulus; responses in the anxious patient group had consistently lower amplitudes than those in the control group. 4. In both groups, the time taken for 75% recovery of the baseline pupil diameter following a light stimulus was linearly related to the logarithm of the light intensity; the 75% recovery times did not differ significantly between the two groups. 5. It is suggested that these results are consistent with a greater supranuclear inhibition of the parasympathetic oculomotor reflex arc in the anxious patients. PMID- 2223417 TI - The effect of miglitol and acarbose after an oral glucose load: a novel hypoglycaemic mechanism? AB - 1. Alpha-glucosidase inhibitors such as miglitol and acarbose lower blood glucose after a starch load in healthy volunteers and diabetic patients by interfering with the conversion of disaccharide to monosaccharide in the gastrointestinal tract. 2. The effect of placebo, 100 mg miglitol and 100 mg acarbose given 30 min prior to a 75 g oral glucose load was investigated in nine healthy Caucasian volunteers. 3. Miglitol produced a statistically significant fall in post-peak blood glucose levels when compared with placebo and acarbose. Serum insulin did not change significantly. 4. As miglitol is well absorbed and acarbose is not, it is suggested that miglitol has a systemic hypoglycaemic effect, probably related to its close structural similarity to glucose, which warrants further investigation. PMID- 2223419 TI - A correlation between severity of migraine and delayed gastric emptying measured by an epigastric impedance method. AB - 1. This study examined the ability of a bioimpedance method to detect the delay in gastric emptying which occurs during attacks of migraine. 2. In 64 non migraineur control patients and 46 migraine patients outside an attack, gastric emptying rates were within the predicted normal range. 3. In contrast, rates in 14 migraineurs during 20 attacks were delayed during severe or moderate attacks and were significantly correlated with the intensity of headache, nausea and photophobia. 4. The epigastric impedance method was generally well tolerated by patients and appears to merit further investigation as a clinical method of monitoring gastric emptying of liquids. PMID- 2223418 TI - Comparative effects of quinine and quinidine on glucose metabolism in healthy volunteers. AB - 1. To investigate the relative effects of quinine and quinidine on glucose metabolism, 11 healthy males aged 17-32 years were given three separate 1 h intravenous infusions; normal saline alone, quinine dihydrochloride 10 mg base kg 1 body weight (BW) in normal saline, and quinidine dihydrochloride 10 mg base kg 1 BW in normal saline. A constant infusion of 5 mg glucose kg-1 ideal BW min-1 was given for 1 h before and during each study. 2. Assessment of pancreatic beta cell function and tissue insulin sensitivity from plasma glucose and insulin concentrations at the end of the first hour using the Continuous Infusion of Glucose with Model Assessment (CIGMA) technique confirmed normal glucose tolerance for each subject on each test day. 3. Plasma glucose concentrations at 1 h were similar to those at 2 h. There was no significant difference between the plasma glucose profiles during the three infusion regimes (P greater than 0.05). Plasma insulin rose significantly during the second hour (P less than 0.0001); increments after quinine (geometric mean [-1 s.d- +1 s.d.]; 47.0 [27.8-79.4] mu l 1) were significantly greater than those after quinidine (19.8 [6.1-65.2] mu l-1) and saline (7.5 [0-21.5] mu l-1; P less than 0.05). Plasma quinine concentrations at the end of the infusion (6.5 +/- 4.4 mg l-1) correlated with insulin increments during the second hour (r = 0.662, P = 0.028) and were significantly greater than those of quinidine (3.0 +/- 0.8 mg l-1; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223420 TI - Bioactivation of dapsone to a cytotoxic metabolite: in vitro use of a novel two compartment system which contains human tissues. AB - 1. A two compartment system, comprising two adjacent teflon chambers separated by a semi-permeable membrane, has been devised with which to investigate the generation of drug metabolites that are toxic to human cells in vitro. 2. Compartment A contained a drug-metabolising system (human liver microsomes +/- NADPH) and compartment B contained target cells (human mononuclear leucocytes). The semi-permeable membrane retained protein (m.w. greater than 10,000) but allowed equilibration (within 1 h) of drug and drug metabolites, during which time cells remained viable. 3. Incubation of dapsone (100 microM) with human microsomal protein (2 mg ml-1) and NADPH (1 mM) in compartment A caused cell death (8.7 +/- 1.8%) in compartment B, which was reduced significantly (P less than 0.05) by the addition of glutathione (500 microM). Dapsone in the absence of NADPH was not cytotoxic. 4. Chemical analysis showed the presence of dapsone hydroxylamine as the only stable metabolite in both compartment A (5.2 +/- 0.4% incubated drug) and compartment B (3.5 +/- 0.5%). 5. Irreversible binding of dapsone to cells was significantly (P less than 0.05) reduced by omission of NADPH (85 +/- 13 pmol/10(6) cells) or addition of glutathione (103 +/- 9) compared with control values (153 +/- 51). PMID- 2223421 TI - Conjugation pathways in liver disease. AB - 1. The activities of microsomal glucuronyltransferase and thiomethyltransferase, and those of cytosolic sulphotransferase, acetyltransferase, glutathione transferase and thiomethyltransferase were measured in abnormal (cirrhosis and chronic hepatitis) and normal livers. 2. Glucuronyltransferase and sulphotransferase were investigated with 2-naphthol and ethinyloestradiol as substrates. p-Aminobenzoic acid, benzo(a)pyrene-4,5-epoxide and 2-mercaptoethanol were the substrates of acetyltransferase, glutathione transferase and thiomethyltransferase, respectively. 3. Enzyme activities are expressed as nmol min-1 incubation mg-1 protein and the averages (+/- s.d.) are given. With 2 naphthol as substrate, the glucuronyltransferase activity was 6.55 +/- 4.10 (abnormal liver, n = 33) and 7.81 +/- 4.02 (normal liver, n = 26) (NS); whereas sulphotransferase activity was 0.28 +/- 0.18 (abnormal liver, n = 35) and 0.68 +/ 0.43 (normal liver, n = 26) (P less than 0.01). Glucuronyltransferase activity towards ethinyloestradiol was 102.5 +/- 56.9 (abnormal liver, n = 30) and 107 +/- 59.9 (normal liver, n = 26) (NS), whereas sulphotransferase activity was 57.2 +/- 36.0 (abnormal liver, n = 35) and 122 +/- 67.6 (normal liver, n = 28) (P less than 0.01). Acetyltransferase activity was 0.84 +/- 0.83 (abnormal liver, n = 35) and 3.84 +/- 1.65 (normal liver, n = 26) (P less than 0.01). Glutathione transferase activity was 0.83 +/- 0.68 (abnormal liver, n = 35) and 2.90 +/- 1.59 (normal liver, n = 25) (P less than 0.01) and thiomethyltransferase activity was 1.00 +/- 0.69 (abnormal liver, n = 34) and 3.99 +/- 1.49 (normal liver, n = 25) (P less than 0.01). 4. Liver disease lowers the activities towards the substrates studied of sulphotransferase, acetyltransferase, glutathionetransferase and thiomethyltransferase but not that of glucuronyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223422 TI - A comparison of a short half-life marker (low-dose isoniazid), a long half-life pharmacological indicator (low-dose phenobarbitone) and measurements of a controlled release 'therapeutic drug' (metoprolol, Metoros) in reflecting incomplete compliance by volunteers. AB - 1. Although, long half-life compounds appear to be more appropriate pharmacological indicators of compliance with treatment, short half-life markers or measurements of short half-life therapeutic drugs are frequently used. 2. We have compared the usefulness of low-dose phenobarbitone (a long half-life indicator), low dose isoniazid (a short half-life marker) and controlled release metoprolol (Metros) (a controlled release formulation of a short half-life 'therapeutic' drug) in seven volunteers with simulated partial (two thirds) compliance. 3. Detection of isoniazid metabolites in urine had an 83% sensitivity and 94% specificity for detecting ingestion within the previous 24 h and 100% sensitivity and 82% specificity for detecting ingestion within the past 6 h but gave no indication of the longer term pattern of compliance. 4. At 28 days (a time when steady-state would be obtained for all three drugs) phenobarbitone plasma levels were 70% (66-76%)--median and interquartile range--of the expected steady-state level if compliance had been complete. Corresponding figures for metoprolol were 82% (37-100%). 5. Measurement of phenobarbitone was much superior to isoniazid or metoprolol measurements in reflecting partial compliance over the previous 1 to 4 weeks. PMID- 2223423 TI - A prospective study of cyclosporine concentration in relation to its therapeutic effect and toxicity after renal transplantation. AB - 1. Cyclosporine (CsA) concentrations in plasma and whole blood were monitored prospectively in 66 consecutive kidney transplant recipients for 6 months after transplantation or until graft loss. Immunosuppression was based on treatment with CsA and prednisolone in 27 patients and CsA, azathioprine and prednisolone in 39 patients. 2. Whole blood and plasma samples (separated at 37 degrees C) were collected 10-12 h after CsA dosage twice weekly over the first 3 months and thereafter once weekly. CsA concentrations were measured by high pressure liquid chromatography (h.p.l.c.) in plasma, by specific and non-specific monoclonal radioimmunoassays (r.i.a.) in whole blood, and by polyclonal r.i.a. and polyclonal fluorescence polarization immunoassay (f.p.i.a.) in whole blood and plasma. 3. There were no differences between the treatment schedules regarding graft or patient survival, occurrence of acute rejection, nephrotoxicity or infection. 4. CsA concentrations were significantly lower at the time of acute rejection than one week earlier based on all of the analytical methods used except f.p.i.a. 5. The lowest CsA concentration, recorded during the first month after transplantation, was significantly lower in patients with than in patients without experience of acute rejection episodes when the CsA concentrations were measured by polyclonal r.i.a. in whole blood and plasma and by specific and non specific monoclonal r.i.a. in whole blood, but not by h.p.l.c. in plasma or polyclonal f.p.i.a. in whole blood or plasma. 6. The highest CsA concentration recorded during the second post-transplantation month, was higher in patients with acute nephrotoxicity than in those without nephrotoxicity when CsA was measured by specific monoclonal r.i.a. in whole blood (471 +/- 409 ng ml-1 vs 327 +/- 150 ng ml-1, P less than 0.05), but not by the other methods. 7. The mean plasma h.p.l.c. concentration of CsA measured by h.p.l.c. during the first month after transplantation was significantly higher in patients who suffered from systemic infection than in patients who did not (116 +/- 70 ng ml-1 vs 82 +/- 52 ng ml-1; P less than 0.05). 8. Thus, significant relationships between CsA concentrations and clinical events were apparent using assay methods specific for CsA as well as using polyclonal r.i.a., but not using polyclonal f.p.i.a. When h.p.l.c. was used, however, plasma drug concentrations were often below the limit of determination. Our results suggest that specific analysis of CsA in whole blood allows the best distinction between patients who respond favourably and less favourably to treatment with CsA. PMID- 2223424 TI - Actions of zopiclone and carbamazepine, alone and in combination, on human skilled performance in laboratory and clinical tests. AB - 1. Possible interactions of zopiclone and carbamazepine on human skilled performance were studied in a randomized, double-blind, crossover trial with 12 healthy young subjects. 2. Psychomotor performance (coordination, reactions, attention, cognition) and subjective effects (VAS) were measured and venous blood sampled before and 1.5, 3, 4.5 and 6 h after single oral doses of placebo, 7.5 mg of zopiclone and 600 mg of carbamazepine, which were given alone or combined. Clinical test for drunkenness (CTD) was done 2 and 5 h after drug intake. 3. Both zopiclone and carbamazepine, when administered alone, impaired performance on laboratory tests, the decrements being recorded 1.5 to 6 h after intake. In line with the plasma concentrations, the zopiclone effects peaked earlier (at 1.5 h) and lasted for a shorter time than those of carbamazepine. Zopiclone had a more pronounced effect on perceptual and cognitive functions (digit substitution) and it affected extraocular muscle tone (Maddox wing), whereas carbamazepine had stronger effects on attention. Additive pharmacodynamic actions were found in most tests after the combined treatment with zopiclone and carbamazepine. 4. CTD proved to be less sensitive than the laboratory tests in revealing drug-induced decrement of performance after administration of one agent alone. However, it revealed the combined decremental effects of zopiclone and carbamazepine. 5. When the drugs were given together, the absorption of drugs was retarded. Carbamazepine-10,11-epoxide levels were lower after intake of the drug combination than those measured after intake of carbamazepine alone. 6. The results suggest that the clinical tests developed to detect alcohol effects do not necessarily reveal drug-induced impairment of performance. PMID- 2223425 TI - Daytime wakefulness following a bedtime oral dose of zolpidem 20 mg, flunitrazepam 2 mg and placebo. AB - 1. The effects of zolpidem 20 mg, flunitrazepam 2 mg and placebo, administered at bed time, were studied in 12 healthy young male volunteers. 2. The assessments included, at awakening, subjective ratings of overnight sleep, cognitive function, psychomotor performance (digit symbol substitution, choice reaction time, flicker fusion threshold), subjective ratings of alertness, and plasma assay of residual drug concentration. Daytime sleep propensity during the day after dosing was evaluated with the multiple sleep latency test. 3. Compared with placebo, both active drugs improved subjective assessment of the ease of getting to sleep. At awakening, under flunitrazepam treatment, the reduction of performance, on memory and psychomotor tests, paralleled an increased subjective rating of sleepiness, but zolpidem treatment left subjects unimpaired compared with placebo. Similarly, daytime sleep propensity was enhanced throughout the following day under flunitrazepam treatment, but not under zolpidem treatment. Plasma assay for residual drug concentration at awakening found significant amounts of flunitrazepam and marginal amounts of zolpidem. 4. Results indicate that zolpidem 20 mg is devoid of residual effects in a range of tasks that were sensitive enough to demonstrate a prolonged wakefulness impairment following flunitrzepam 2 mg in healthy volunteers. PMID- 2223428 TI - The heart rate-PR interval relationship: a model for evaluating drug actions on SA and AV nodal function. AB - The relationship between heart rate (HR) and PR interval (PR) has been investigated to determine inter-subject variability, within-subject variability and potential reference standards. Eight healthy male volunteers underwent upright graded submaximal treadmill exercise during eight separate study sessions. All subjects exhibited statistically significant negative linear relationships between PR and HR. Although there was considerable inter-subject variability, there was little within-subject variability in the interpolated PR at HR between 80 and 120 beats min-1. The HR-PR regression model has greatest validity within this HR range and for individual subjects rather than pooled or group data. PMID- 2223426 TI - Induction of polymorphic 4'-hydroxylation of S-mephenytoin by rifampicin. AB - Studies were performed in 13 healthy subjects to determine whether treatment with rifampicin results in induction of the metabolism of mephenytoin. Daily dosing with 600 mg rifampicin for 22 days caused a three to eightfold increase in the 0 8 h urinary R/S ratio of mephenytoin following oral administration (100 mg) of racemic drug to extensive metabolizers of the anticonvulsant. This was accompanied by a 40 to 180% increase in the 0-8 h urinary excretion of the 4' hydroxy metabolite. Four weeks after discontinuing rifampicin, both metabolic indices had returned to their baseline values. By contrast, rifampicin had no effect on either measures of metabolism in subjects of the poor metabolizer phenotype. Thus, it appears that the activity of the enzyme (P-450 MP) mediating the genetically determined 4'-hydroxylation of S-mephenytoin can be significantly modulated by enzyme inducing agents such as rifampicin and possibly environmental agents with a similar ability. PMID- 2223427 TI - Single-dose effects of ibopamine hydrochloride on renal function in patients with congestive heart failure. AB - To examine the renal effects of ibopamine HCl we evaluated 15 patients with New York Heart Association Class II-III congestive heart failure and mild renal insufficiency (creatinine clearance [CLcr] = 45-85 ml min-1). Diuretics and vasodilators were withheld and a sodium (Na+)-restricted diet was initiated. All patients exhibited positive Na+ balance at the time of evaluation. Hourly urine volumes, urine chemistries, serum chemistries, PAH and inulin/iothalamate clearances were determined 2 h pre and 4 h post a single 200 mg oral dose of ibopamine. Effective renal plasma flow, creatinine clearance, filtration fraction, and the fractional excretion of sodium and potassium were not significantly altered postdose. A significant increase in urine output and decrease in urine osmolality were seen at all time points postdose. A significant reduction in serum potassium (2 and 3 h) and blood urea nitrogen (1, 3 and 4 h) concentrations occurred. Measurements of glomerular filtration rate by inulin or [125I]-iothalamate produced differing results in the patient groups studied. We conclude that a single dose of ibopamine does not produce significant improvements in renal function in patients with congestive heart failure, mild renal insufficiency and positive sodium balance. PMID- 2223429 TI - Nitrendipine therapy in asthmatic subjects. AB - Nitrendipine was given to eight patients with chronic stable asthma prior to a histamine challenge study and compared in a double-blind cross-over fashion with placebo. There were no significant differences in either the bronchoconstrictor effects of histamine, or in oxygen saturation during the histamine challenges, suggesting that nitrendipine should be safely tolerated if used to treat hypertension in patients with airflow obstruction. PMID- 2223431 TI - Nicardipine does not influence the pharmacokinetics and pharmacodynamics of atenolol. PMID- 2223430 TI - Effect of activated charcoal on frusemide induced diuresis: a human class experiment for medical students. AB - We have introduced to the course in pharmacology for medical students a simple human experiment that demonstrates the efficacy of activated charcoal in gastrointestinal drug binding. Sixty-one students were given 40 mg frusemide with water, water only, or 40 mg frusemide and 8 g activated charcoal with water either immediately or after different time intervals. The diuretic effect of frusemide was totally prevented when taken together with charcoal, but became apparent gradually when charcoal was taken after a lag time. This experiment is simple to carry out and demonstrates vividly the treatment principles of acute intoxications. PMID- 2223432 TI - Calcium antagonists in the management of subarachnoid haemorrhage. AB - The development of delayed cerebral ischaemia and hence neurological deficit remains a serious problem following subarachnoid haemorrhage. Over recent years, attention has focussed on the use of the dihydropyridine class of calcium channel blocking agents ("calcium antagonists"), in particular nimodipine, as drug therapy in the prophylaxis and treatment of this condition. The theoretical basis for this is briefly discussed and then the clinical experience of the use of calcium antagonists following subarachnoid haemorrhage reviewed. In particular, attention is focussed on the randomised controlled trials that have eventually been able to show that such treatment is beneficial, both in terms of reduction of ischaemic deficit attributable to cerebral "vasospasm" and in clinical outcome, when given prophylactically, although not apparently therapeutically once deficit has developed. The evidence of the mode of action of calcium antagonists in this situation is discussed, again with particular reference to clinical data obtained in situ in the course of such trials. Although the mechanism of action remains unclear, it appears likely that it is at least in part due to the selective cerebral vasodilation induced by these compounds. The necessity for large well-controlled, prospective, randomised clinical trials in the assessment of therapeutic efficacy is stressed. PMID- 2223433 TI - Primary malignant bone tumors. PMID- 2223434 TI - Secondary bone tumors, myeloma, cryoglobulinemia, and paraproteinemias. PMID- 2223435 TI - Soft tissue tumors. PMID- 2223436 TI - Clinical disorders of vitamin D, renal osteodystrophy, and hypophosphatasia. PMID- 2223437 TI - Miscellaneous synovial lesions. PMID- 2223438 TI - Iatrogenic bone malignancy and pseudomalignancy. PMID- 2223439 TI - Hip surgery in adults. PMID- 2223440 TI - Surgical treatment of septic arthritis and infected prostheses. PMID- 2223441 TI - Knee surgery. PMID- 2223442 TI - Shoulder surgery. PMID- 2223443 TI - Elbow, wrist, and hand surgery. PMID- 2223444 TI - Surgical management of cervical spine instability. PMID- 2223445 TI - Surgical correction of severe forefoot deformities in rheumatoid arthritis. PMID- 2223446 TI - Scoliosis. PMID- 2223447 TI - Metabolic bone disease. PMID- 2223449 TI - Vasculitic syndromes. PMID- 2223448 TI - Parathyroid gland disease and hypercalcemia. PMID- 2223450 TI - Tumors of bones and joints. PMID- 2223451 TI - Orthopedic conditions and surgery. PMID- 2223452 TI - Avascular necrosis of bone. PMID- 2223453 TI - Collagen disorders and skeletal dysplasias. PMID- 2223454 TI - Osteoporosis. PMID- 2223455 TI - Fluorosis, osteopetrosis, and ectopic calcification. PMID- 2223457 TI - Giant cell arteritis. PMID- 2223456 TI - Wegener's granulomatosis and other systemic granulomatous conditions. PMID- 2223458 TI - Cutaneous vasculitis, hypersensitivity vasculitis, erythema nodosum, and pyoderma gangrenosum. PMID- 2223459 TI - Polychondritis and Behcet's disease. PMID- 2223461 TI - Paget's disease and fibrous dysplasia. PMID- 2223460 TI - Buerger's disease and inflammatory aspects of atherosclerosis. PMID- 2223462 TI - Kawasaki disease. PMID- 2223463 TI - Vasculitic syndromes associated with other rheumatic conditions and unclassified systemic vasculitis. PMID- 2223464 TI - Benign tumors of bone. PMID- 2223465 TI - [Surgical treatment of hydatid cysts of the hepatic dome ruptured into the thoracic cavity]. AB - Two cases of hydatid cyst of the hepatic dome, complicated by rupture in the thoracic cavity, are reported. The Authors stress the frequency of human hydatidosis, still high in Italy, and the severity of the above mentioned complication. Surgical treatment is also discussed. PMID- 2223466 TI - [Autologous dermal graft in the treatment of hernia of the abdominal wall. A clinical contribution]. AB - The A.A. after reporting the different methods of treatment of the abdomen wall herniation relate about the advantages of autologous dermis graft. Pointing out their experience they conclude that dermis for its perfect tolerability and absence of complications gives considerable probabilities of success. PMID- 2223467 TI - [Postoperative hypo-osmolar coma: presentation of a clinical case]. PMID- 2223468 TI - [Villous adenoma of the rectum. Review of the literature and personal experience]. AB - Potential malignancy of rectal villous adenomas is referred as varying from 20 to 30%; an appropriate surgical excision is required in order to insure an effective cancer prophylaxis and to improve the accuracy of the pathologic assessment. The Authors review their series concerning 15 patients with one or more polyps of villous type, located at the lower third of the rectum and with precise indications for transanal excision. In 13 cases histology demonstrated the presence of an adenoma with different grade of dysplasia, which simply entered a follow-up together with a case of an adenoma with carcinoma in situ. The latter, because of the presence of invasive carcinoma, underwent radical surgery. No postoperative morbidity was observed. Recurrence rate was 8%. After an accurate review of the Literature, a radical management of the rectal villous tumour performed on routine basis seems unjustified. The Authors suggest the indication for a modern proceeding. PMID- 2223469 TI - [Angiodysplasia of the colon]. AB - The Authors report their experience with a case of angiodysplasia of the colon. It is outlined how these lesions can be demonstrated by angiography and colonoscopy. The pathophysiology, diagnosis and management are discussed as well. PMID- 2223470 TI - [PTC with percutaneous biliary drainage in obstructive jaundice. Considerations on the diagnostic validity and reducing of surgical morbidity and mortality]. AB - Indications, diagnostic validity, and effective reduction of surgical mortality and morbidity of the PTC with PTBD in obstructive jaundice are evaluated. A brief note on the existing controversy in this particular field introduces to the Author's personal opinion based on a small series of 13 cases treated from April '87 to January '89. PMID- 2223471 TI - [Integrated anastomosis using the Knight and Griffen technique]. AB - The widespread use of mechanical staplers in gastrointestinal surgery has recently resulted in a simpler and faster operative technique. The double-stapled anastomosis (Knight and Griffen, 1980) seems to further simplify the technique of colo-rectal anastomosis, with reduced risks of pelvic contamination. Moreover, this technique can be used to reconstitute bowel continuity following an Hartmann's procedure or to perform an ileo-rectal anastomosis. The results obtained in 21 patients treated by this technique are presently reported. PMID- 2223472 TI - [Use of mechanical staplers in surgical therapy of morbid obesity]. AB - The Author reports the experience of the III Surgical Department of the University of Milan on stapling devices in bariatric surgery. The use of stapling devices is now almost irreplaceable for some surgical interventions like gastroplasty, jejuno-ileal bypass, and intestinal bypass revision because staplers simplify and shorten operating procedures, also reducing surgical risk. PMID- 2223473 TI - [Use of a new compression circular mechanical stapler in surgery of the large intestine]. AB - Clinical application in surgery of the large bowel of a compression anastomotic device developed by the Authors is described. The device consists of three plastic rings carried by an instrument that assembles the rings while the bowel is being joined. The rings remain by the anastomotic site until complete healing of anastomosis, then fall into the intestinal lumen and are evacuated with the feces. Sixty-nine patients underwent large bowel anastomosis using this device in our department from May 1986 through June 1989. Forty percent of the anastomoses were located at less than 8 cm from the anal verge. Five intraoperative diverting colostomies were performed (7.2%). The rings were evacuated in average 11 days after the operation, with no or very little discomfort. Operative mortality was 1.4% (one patient died of myocardial infarction). Anastomotic complications were: two (2.8%) clinical and two (2.8%) subclinical dehiscences. This initial clinical experience shows that the anastomotic device is reliable. PMID- 2223475 TI - [A bladder tube construction using a stapler with absorbable stitches (Poly CS 57)]. AB - A new technique for the construction of a bladder tube, using a Poly CS-57 stapler, has been tested on six pigs. With this procedure the operative time is shortened without complications. In fact, no crystal formation, dehiscence or infection was observed during a 3 month follow-up. PMID- 2223474 TI - [Stapling techniques in exeresis surgery of bronchogenic carcinoma]. AB - From January 1983 to October 1989, 221 bronchogenic carcinomas were surgically treated at our Department. Different stapling techniques were employed in 153 cases: 138 stapled sutures of main and lobar bronchi, 33 stapled parenchymal sutures and 21 stapled sutures of the pulmonary artery. Stapling-related complications were observed in 3 patients: 1 bronchopleural post-pneumonectomy fistula (0.72%); 2 persisting air leakages following stapled parenchymal suture (6%). The use of vascular staplers, though, has never been associated with complications. The advantages related to the use of stapling devices are represented by lower air leakage and bleeding rates, with a reduced operative trauma; on the other hand, disadvantages seem to be more theoretical than realistic. At our Department stapling devices nowadays represent the choice in thoracic surgery either for main and lobar bronchi or parenchymal sutures. PMID- 2223477 TI - [Comparison of manual and mechanical anastomosis in colorectal surgery]. AB - Between 1981 and 1989, 494 patients had anastomosis involving the colon or rectum (233 ileo-colonic, 156 colo-colonic, 96 colo-rectal and 9 ileo-rectal) in our Institute. 383 patients had manual anastomosis (Group 1), 111 patients had stapled anastomosis (Group 2). There was no statistically significant difference when comparing major anastomotic complications, reoperations and operative mortality of stapled and manual anastomoses. In group 1 a significant increase in complication was related to the presence of obstruction (p. less than 0.01), and to emergency surgery (p less than 0.01). In Group 2 malnutrition had a significant effect on anastomotic complications (p less than 0.01). Therefore, colonic obstruction, emergency surgery and malnutrition have a significant role in anastomotic complications, and particular care should be taken when these factors are present. PMID- 2223476 TI - [Digestive reconstruction using mechanical staplers after total gastrectomy]. AB - From 1980 up to nowadays, after total gastrectomy for gastric cancer, the intestinal continuity was assured by oesophago-jejunostomy and oesophago duodenoplasty using stapling devices. Two patients died for causes not related to the technique, and other two patients developed a stenosis of the oesophago jejunostomy, which was easily managed by endoscopic dilatation. In one patient a partial dehiscence of the oesophago-jejuno-anastomosis was treated by total parenteral nutrition. The Authors have systematically adopted mechanical sutures after total gastrectomy. However, possible intraoperative accidents and complications should not be underestimated, although most of them may be due to the operator's inexperience or stapler misuse. PMID- 2223479 TI - [Mechanical duodenopancreatectomy]. AB - Pancreaticoduodenectomy with stapler devices is presented. Three patients affected by pancreatic malignant neoplasm were successfully treated, and the technique used is here reported. PMID- 2223478 TI - [Manual versus mechanical sutures in gastric surgery in cancer]. AB - The Authors, on the basis of their experience in San Camillo Hospital of Rome, compare the results between manual and mechanical sutures in 597 gastric cancers operated in the last 12 years. They confirm that at present staplers are of great reliability. PMID- 2223480 TI - [Mechanical anastomosis without purse-string suture in esophageal surgery]. AB - A new surgical procedure for oesophago-enterostomy using staplers without purse string suture is described. This technique is possible only using the CEEAP stapler, thanks to its new technical features. PMID- 2223481 TI - [Mechanical staplers in resective surgery of the pancreas]. AB - In this study 8 pancreatic resections were performed using the Autosuture stapler. No fistula developed among 5 cases of distal pancreatectomy, conversely 2 pancreatic fistula occurred in 3 cases of pancreaticoduodenectomy; one patient died for fistula. It is concluded that distal pancreatectomy with staplers is a reasonable and safe alternative to pancreaticojejunostomy, and may be preferred because of its facility and rapidity. Staple closure of the transected pancreas in pancreaticoduodenectomy doesn't seem to be so safe and further evaluation is needed. PMID- 2223483 TI - [Mechanical staplers in exeresis surgery of pulmonary cancer]. AB - Surgical stapling devices are widespread in many branches of surgery and are employed with success in thoracic surgery. Our experience is in line with that of other Authors: stapling of the bronchus is faster, does not contaminate the operative field and reduces the incidence of bronchopleural fistulas (4.76% to 1.59%). Parenchymal stapling is indicated for resection of bullae, metastases and peripheral lesions. The mechanical suture is air-tight and faster than manual suture. Pulmonary vessels may also be closed mechanically; however, we do not advocate the use of stapling devices especially in the closure of the pulmonary artery. PMID- 2223482 TI - [100 cases of bronchial mechanical sutures]. AB - The Authors report their experience with stapler model T.A. 30 in lung resections; 100 stapled sutures were carried out in the IV Surgical Department of the University "La Sapienza" of Rome, during the period 1980-88. The use of stapler with two rows of staples allows a secure closure of the bronchial stump. Moreover, it prevents granulomas caused by suture material. The bronchopleural fistulas, serious complications of manual suturing, did not occur. Finally, this method is simpler and rapidly feasible in comparison with classic ones. PMID- 2223484 TI - [In vitro study of Staphylococcus epidermidis adhesiveness to suture materials]. AB - In surgical divisions, where you can find the highest percentage of hospital infections, the surgical wounds are definitively the most frequent localization. The aim of our study was to evaluate whether bacterial-biomaterial interactions could influence the growth of infections in sutured tissues. We prepared a method for in vitro bacterial adhesiveness testing based on turbidimetric analysis. The results obtained show a different grade of bacterial adhesion in relation to physical and chemical characteristics of the material examined. PMID- 2223485 TI - [Influence of suture materials on cell viability: a comparative experimental study]. AB - Among the conditions that a material must satisfy to be considered biocompatible, most important is the non negative influence on the cellular viability of the surrounding tissue (cytocompatibility). The aim of our work was to evaluate in vitro, whether different types of materials (usually used in surgery), alter the viability parameters or the morphological characteristics of the cultured cells in contact with them. PMID- 2223486 TI - [Gastroduodenal surgery using mechanical staplers: our experience]. AB - Results of 71 operations of the gastroduodenal tract performed with stapling devices are reported (51 for malignant diseases and 20 for benign diseases). 20 total gastrectomies, 21 Billroth II gastrectomies, 17 Roux en-Y gastrojejunoplasty, 6 Billroth II to Roux-ex-Y-conversion and 7 palliative gastroenteroanastomosis were performed, using TA, GIA and EEA stapling instruments. The analysis of the reported data brought us to some considerations regarding the safety and versatility of mechanical viscerosynthesis, also in relation to some technical aspects. PMID- 2223487 TI - [J-reservoir in the treatment of ulcero-hemorrhagic rectocolitis]. AB - The Authors report their experience on ileal-anal anastomosis with a J-pouch. A videotape illustrates the surgical technique. At last functional results are shown. PMID- 2223488 TI - [Malfunctioning of linear staplers as a cause of gastro-gastric fistula in vertical gastroplasty]. AB - The Authors reviewed their series of patients submitted to VBG in order to investigate the rate and cause of gastric partition disruption. This complication was found only in patients who had the gastric partition done by means of a double application of TA-90. No gastric partition disruption was found in those patients in which TA-90-B was used. The partition breakdown might be due to occasionally defective closure mechanism in the traditional staplers. PMID- 2223489 TI - [The duodenal "Y" proximal jejunostomy: the reason of a new reconstructive choice after gastric surgery]. AB - The Author reports a new reconstructive technique after gastric surgery pointing out its advantages confirmed by few clinical cases. Some technical improvements are suggested. PMID- 2223490 TI - [Use of fibrin glue in the treatment of entero-cutaneous fistulas]. AB - The Authors present methods and results of the treatment of chronic fistulas complicating abdominal surgery in 5 patients. The use of human fibrin glue is described and its therapeutical usefulness is pointed out. PMID- 2223491 TI - [Automatic sutures in bronchopulmonary surgery]. AB - Efficacy of automatic staplers in broncho-pulmonary surgery was evaluated in a series of 316 consecutive patients. The results confirm that utilization of staplers has drastically reduced the incidence of post-resection bronchial fistulae; moreover on parenchymal tissue such instruments guarantee excellent haemostasis and air tightness. On the contrary, indications for their use on pulmonary vessels seem to be very limited. PMID- 2223492 TI - [Our experience in the use of mechanical staplers in the execution of step-by step subtotal gastrectomy]. AB - The Authors describe their reconstruction technique after a "step" gastric resection for peptic or neoplastic pathology. The use of staplers such as TA 30 or GIA for the duodenum is reported. After skeletonizing the lesser curve up to the cardias by sectioning the left gastric artery at its origin and up to the penultimate short vessel on the greater curve, the stomach is resected distally to this two points using a TA90 staplers. So it is possible to remove the greater part of the acid-secreting area in order to avoid ulcers of the anastomosis or of the gastric stump, and also to achieve a complete lymphadenectomy in case of neoplasm. Then a Roux-en-Y gastro-jejunal anastomosis is performed using an EEA28 circular stapler. The jejunal stump is closed with a TA30. Finally, a manual jejuno-jejunal anastomosis is made at least at 50 cm from the previous one. From November 1987 to January 1989, 13 patients were operated: 9 for peptic ulcer and 4 for antrum neoplasms. There were no complications during and after the operations. Mortality was 0%. The patient, usually starts eating on the 6th or 7th day after operation, and is discharged on the 10th day. After 6 months an EGD scopy is required: the 8 performed till now have demonstrated excellent anastomosis and no peptic lesions. Scintigraphic evaluations and pH monitoring are still in course to define the gastric stump acid secretion and the absence of biliary reflux. PMID- 2223493 TI - [Use of mechanical staplers in gastric resection]. PMID- 2223494 TI - [Mechanical staplers. Our experience]. AB - The Authors report their experience concerning 237 stapled sutures performed during 93 gastro-intestinal operations. Intraoperative technical advantages are described and improved postoperative courses are outlined; in particular earlier recovery of intestinal function, minimal rate of complications and 11-day average post-operative stay are reported. PMID- 2223495 TI - [Definite colostomy using a circular stapler: a technique to be reconsidered]. AB - Personal experience on a particular utilization of circular stapler is reported. At the beginning the fast and easy execution emphasized its use. However, the constant appearance of a late complication was observed, i.e. the progressive stenosis of the stoma. This event occurred even when maximal size of the instrument was used and it reappeared after repeated procedures of instrumental or surgical dilatation. The effective validity of this technique was evaluated by the Authors. On the other hand, the Burk alternative technique, with a second purse-string on the cutaneous ring seems to prevent the stenosis. However, it is slow and difficult as traditional procedure. The causes of the neostoma stenosis performed by circular stapler, reported by the Authors in 100% of cases, are easily explained with the absence of biological barrier of colonic mucosa that normally prevents excessive tissue growth. PMID- 2223496 TI - [Slowly reabsorbable suture threads in arterial microsurgery]. AB - Authors present the results of an experimental research to evaluate the effectiveness of a slow resorbable suture (Polyglactyn 910) in arterial microsurgery. Healing of vascular wall, histologically evaluated, showed good reliability, compared to other suture materials. PMID- 2223497 TI - [Staplers in bladder sutures]. AB - Staplers are still little used for suturing a cystotomy. The basic reason for this reluctance is the inadvisability of using non-absorbable material in the lumen of the urinary tract, as this may be the nucleus for the formation of stones. It must be remembered, however, that a correct suture of a cystotomy should be carried out in two layers: one internal mucous layer, consisting of a continuous suture of absorbable material, and a more superficial suture of the margins of the vesical detrusor. The latter can be performed with a linear stapler, as it is completely outside the mucous layer. More recently, linear staplers with absorbable staples have appeared on the market, by which cystotomy sutures can be performed in a single layer. PMID- 2223498 TI - [Continent pre-peritoneal uretero-ileostomy with a hydraulic valve. A personal technique]. AB - A continent ileal reservoir has been realized. The reservoir is placed outside the peritoneum, in a pre-peritoneal position, in order to allow its fixation by adhesions to the abdominal wall. Furthermore, a Benchekroun's hydraulic valve, adopted as a continent mechanism, is placed distant from the reservoir, by means of a long anti-peristaltic ileal loop, which further prevents the effects of the reservoir enlargement. The reservoir is made up using 40 cm of detubulized ileum; on the afferent loop (10 cm long) the right ureter is implanted according to the Camey-Le Duc technique, on the efferent loop (25 cm long) the left ureter is implanted according to the same technique. The remaining 15 cm of the ileum are used to realize a Benchekroun's hydraulic valve which is exteriorized by means of a skin stoma, placed on the left abdominal wall. With this technique, 18 patients have been operated; the follow-up period is 3 years for the first cases. PMID- 2223499 TI - [Mechanical staplers in our surgical practice]. AB - On the basis of our experience from 1981 to 1989, advantages of staplers in digestive surgery are reported. Complications such as bleeding and stenosis are not clinically important, however, in most cases, they can be avoided if the instruments are properly used. PMID- 2223500 TI - [Personal experience in the area of colorectal anastomoses without protective colostomy]. AB - The Authors report their past 3-year-experience in colorectal anastomosis without protective colostomy. General results in terms of complications and mortality rates are similar if not even better than those referred by the international Literature. PMID- 2223501 TI - [Esophagogastric anastomosis at the inferior cricoid margin]. AB - In esophageal resections, esophagogastric anastomosis can be performed either at cervical or intrathoracic level. A recent paper showed a greater incidence of postoperative leakages in cervical vs. intrathoracic anastomosis (26% vs. 4%). In the present paper we describe 55 cases of esophagectomy with a modified technique of cervical stapled anastomosis, where the incidence of fistula was 5%. PMID- 2223502 TI - [French Association of Viscero-Synthesis: history]. PMID- 2223503 TI - [Realities and prospects of viscero-synthesis]. PMID- 2223504 TI - [Critical considerations on circular staplers]. AB - After a careful review of the literature and a critical evaluation of personal experience on stapling technics in visceral anastomoses, some critical considerations on circular devices are reported. The Authors emphasize the well known qualities of staplers which brought to their routine use in digestive surgery. Some complications exclusively due to an "imperfect" firing of the instrument are then reported. Personal experience on a particular utilization of circular stapler for definitive colostomy is also reported. The Authors finally suggest some simple technical improvements. PMID- 2223505 TI - [Education (university training in mechanical sutures)]. AB - The advances in surgical sciences and their evolution, besides the increasing number of surgical residents and the low availability of the operating-rooms, have made clear the limits of the usual teaching methods and of the integrative theoretical learning instruments. The teaching of viscero-synthesis, particularly mechanical suture training, emphasizes such problems and encourages the development of additional training programmes, including simulation, before the admittance to operative procedures. PMID- 2223506 TI - [Experiences with mechanical staplers: hemorrhoidectomy using a circular stapler]. PMID- 2223507 TI - [Esophagojejunal anastomosis after total gastrectomy]. AB - The Authors discuss the technical criteria of digestive reconstruction after total gastrectomy for gastric cancer. Usually they employ stapling devices which are easy and quick to use and give good technical results. Performing a Roux-en-Y with an end-to-side esophagojejunostomy a circular device is preferred and a linear cutter for a side-to-side jejunojejunal anastomosis is used. Alternatively the jejunojejunal anastomosis may be performed with a circular and a linear stapler. Between 1970 and 1989, out of 160 total gastrectomies for cancer, 2 dehiscences were recorded in 103 mechanical anastomosis and none out of 57 manual anastomosis (p: n.s.); stenosis was observed in 2 cases after mechanical esophagojejunostomy and in none after manual anastomosis. PMID- 2223508 TI - [Experimental microsurgery: the main technical bases for research]. PMID- 2223509 TI - Veno-venous bypass in experimental liver transplantation: portal-jugular versus caval-portal-jugular. AB - This study was undertaken to compare the changes in physiologic variables caused by the use of two different types of pump-assisted veno-venous bypass during experimental liver transplantation. The experiments, performed on female pigs weighing 30 +/- 2 kg, were divided into two groups depending on the bypass used. During the anhepatic phase a pump-assisted portal-jugular (PJ) bypass was used in Group 1 (n = 8) at a flow rate of 15 ml kg-1-min-1, while a pump-assisted caval portal-jugular (CPJ) bypass was used in Group 2 (n = 8) at a flow rate of 20 ml kg-1-min-1. Intraoperative haemodynamics, pulmonary gas exchange, haematological and serum biochemical parameters were evaluated. Postoperative animal survival rate and complications associated with the bypass used were evaluated. Mean pulmonary artery pressure (Ppa) and pulmonary vascular resistance (Pvr) showed significantly different behaviour in the two groups, whereas the remaining parameters all showed the same trend. Thus an earlier and more substantial increase in Ppa and Pvr values was found in Group 1 when compared to Group 2 during the anhepatic phase. The different behaviour shown by Group 1 may depend on the release of circulating vasoactive substances generated following pelvic venous congestion caused by the temporary clamping of the inferior vena cava. In conclusion, this study indicates that the pump-assisted CPJ bypass is more suitable than the pump-assisted PJ bypass. Furthermore, in order to obtain better results it should be used routinely in porcine liver transplantation. PMID- 2223510 TI - [Aneurysms of the abdominal aorta]. AB - The authors report 73 cases of abdominal aortic aneurysms with particular emphasis to early and long-term results as well as postoperative complications: 4 patients died at admission, 16 were treated with medical therapy, and 53 underwent surgery. Surgical patients were stratified in two groups: 18 emergency cases (group 1) and 35 elective cases (group 2). Early results showed the highest mortality in group 1 cases presenting with shock. Late results, at the end of the follow up, (6 months-8 years), showed a 56.6% 5-year survival rate, with overlapping survival rates after the immediate postoperative period. The most frequent postoperative complications were thrombosis of prosthesis and lymphorrhea. Survival rates of emergency cases were influenced by early diagnosis and prompt aorta clamping. Before surgery an haemodynamic evaluation of all vascular districts seems necessary in elective cases to prevent complications of atherosclerotic disease. PMID- 2223511 TI - [Diverticula of the cecum. Our experience]. AB - On the basis of their experience in right colonic emergencies, the Authors report two cases of diverticular disease presenting with acute abdomen. Pointing out the difficulty of a correct pre- and intraoperative diagnosis, different surgical procedures are analysed. PMID- 2223513 TI - [Intra- and postoperative complications in the surgical treatment of cholelithiasis]. AB - The authors report their experience in biliary tract surgery. From 1974 throughout 1988, 1.186 patients underwent surgery and the commonest operation was cholecystectomy. The most significant complications and the causes of death are reported. Mortality rate was 0.82%. PMID- 2223512 TI - [Pancreatic pseudocysts: a rare complication of the Warren distal splenorenal shunt]. AB - The authors report a case of distal splenorenal shunt with splenopancreatic disconnection complicated by a huge pancreatic pseudocyst. This complication has not been described in the literature so far. The etiology and the opportunity of the splenopancreatic disconnection are discussed. PMID- 2223515 TI - Effect of clindamycin on adherence of coagulase-negative Staphylococcus to surgical nets. AB - The authors studied the effect that a subinhibitory concentration of Clindamycin has on adherence of coagulase negative S. epidermidis to surgical nets. Clindamycin, as expected, interferes with the adhesivity to the nets of coagulase negative S. epidermidis slime producing when sub-MICs are used. The documentation obtained by scanning electron microscope, after treatment of the strains with doses of Clindamycin equal to 1/6 of the MIC after 3 and 6 hours, confirms the anti-adherent effect of the antibiotic. PMID- 2223514 TI - [The reliability of the grading assessment of the biopsy samples in malignant colorectal neoplasms]. AB - The authors evaluate the results of preoperative bioptic grading compared with those obtained from postoperative specimens. Altogether, there was nonagreement in 45% of cases; therefore there is the risk of underestimating the biological aggressiveness of the disease. In fact, 68% of patients who were assessed as G1 in preoperative staging were found to have a higher degree of neoplastic dedifferentiation. PMID- 2223517 TI - [I.V. ketorolac in the therapy of postoperative pain]. AB - Forty-one patients suffering from postoperative pain were admitted to an open, noncomparative trial. A dose of 10 mg of Kerotolac was administered i.v. to patients complaining severe pain. The analgesic efficacy of the drug was evaluated at 5, 15, 30 minutes and at 1, 1.5, 2, 3, 4, 6 hours after injection; the patients were asked to score their pain relief on the VRS comparing the pre injection evaluation to each post-injection period. A significant decrease of pain intensity (less than p 0.01) was observed at 45 minutes after injection. No side effects were observed. These results suggest that Ketorolac can be successfully used in the treatment of postoperative pain. PMID- 2223516 TI - [The use of mammary echotomography in the diagnosis and monitoring of the pregnant and puerperal breast. 3 cases of galactocele]. AB - Three cases of galactocele appeared as breast nodule during lactation are reported. From our experience and the recent literature, ultrasound shows a good reliability for the diagnosis of breast diseases during pregnancy and lactation in spite of oedema and breast turgidity, distinctive of these periods. PMID- 2223518 TI - [Tumors of the testicle]. AB - The authors describe, in the light of the current literature, the clinical, diagnostic, and therapeutic characteristic of testicular cancer. They remark the good results of adjuvant therapy in this type of tumor. PMID- 2223519 TI - Temperature limits of growth, TNase and enterotoxin production of Staphylococcus aureus strains isolated from foods. AB - For 77 strains of Staphylococcus aureus freshly isolated from different foods, growth, enterotoxin and TNase production were determined in intervals of 1.5 degrees C +/- 0.5 degrees C by cultivating them in a temperature-gradient incubator between 5 and 50 degrees C for up to 7 days. All the strains were coagulase, DNase and lysostaphin positive but only 58% formed one or two enterotoxins type SEA, SEB or SEE. All strains grew within 7 days in brain heart infusion and had lower and upper temperature limits for growth and TNase production of between 6.5 and 12.5 degrees C, and 39.5 and 48.5 degrees C respectively. The lower and upper temperature limits for production of enterotoxins were between 14 and 38 degrees C, and between 35 and 44 degrees C respectively. Enterotoxin forming isolates either showed narrow (3 to 4 degrees C) or wide (10 to 20 degrees C) ranges of enterotoxin production, irrespective of their temperature range of growth and TNase production. None of the 12 specific physiological attributes used for differentiation could be correlated to toxin type or the temperature requirement of the toxin production. No correlation between the origin and the physiological characters could be detected. PMID- 2223520 TI - Evaluation and interpretation of data obtained with immunoassays and DNA-DNA hybridization techniques. AB - During the last decade several new analytical techniques have been developed for testing food products and clinical samples. One technique uses sensitive immunoassays such as enzyme-linked immunosorbent assay (ELISA) and latex agglutination. The most important step in developing sensitive immunoassays is the evaluation of the assay for specificity, cross-reactivity and sensitivity. False-negative results can easily be detected by adding known quantities of antigen to the sample. The most appropriate way to detect false-positive results is the specific inhibition of the immunological reaction by addition to the test sample of either synthetic epitopes or anti-idiotype antibodies. The progress in recombinant DNA techniques now offers opportunities for application as analytical tools in food and clinical microbiology. Methods are being developed to detect microorganisms by their nucleic acid sequence using the so-called hybridization procedure. With this technique, labelled DNA fragments (probes) are hybridized with a complementary base sequence present in the microorganism. Foodborne pathogens can be detected by using a probe with a complementary base sequence which codes for toxin production. DNA-DNA hybridization techniques may replace the traditional cultural techniques for assaying pathogenic micro-organisms. However, more experience with these techniques is needed before further evaluation can be given. PMID- 2223521 TI - The bacterial flora of non-carbonated, natural mineral water from the springs to reservoir and glass and plastic bottles. AB - Quantitative and qualitative determinations of the bacterial flora of non carbonated natural mineral water at the most important steps during bottling at a large water source yielded the following results: (i) Colony counts (on 1:10 diluted plate count agar, incubated at 20 degrees C for 14 days) for water of the five springs and the mixed water were less than 1 to 4 cfu ml-1. The Gram negative bacterial flora (n = 50 isolates) showed a very different but constant spring specific species distributions with predominance of either eutrophic fluorescent pseudomonads, oligotrophic non-fluorescent pseudomonads or oligotrophic yellow bacteria. (ii) In the reservoir and immediately after bottling the counts were in the range of 10 cfu ml-1. But nearly 30% of the species of the spring water were no longer detectable and there was a significant increase of Gram-positive bacteria. (iii) After 1 week of storage at 20 degrees C colony counts of more than 10(5) cfu ml-1 were found in plastic bottles, but only about 10(4) cfu ml-1 in glass bottles. Besides, a very distinct change of the composition of the microflora occurred. In glass bottles slow-growing oligotrophic non-fluorescent pseudomonads, yellow bacteria and Acinetobacter predominated. In plastic bottles fast-growing eutrophic and mesotrophic fluorescent pseudomonads, Flexibacter and Acinetobacter were dominating. In mineral water, bottled into thoroughly cleaned glass bottles, colony counts of more than 10(5) cfu ml-1 were found within 4 days. In bottles, cleaned mechanically as usual, the increase was significantly slower with a maximum of only 5 x 10(3) cfu ml-1 after 8 days. The results of inoculation experiments in sterile filtered mineral and distilled water led to the suggestion that the difference between the two types of bottles is caused firstly by an inhibition of growth due to residues of cleaning detergents in the glass bottles. Growth promotion by dissolved organic substances in the plastic bottles only played a minor role. After repairing of the pump at a depth of 300 m in a warm mineral water spring, the colony counts at 20, 37 and 42 degrees C on 1:10 diluted and normal plate count agar increased beyond the limits required by the EC directive for mineral water stored a month. Then colony counts decreased slowly and reached the initial level after 1 year, except for the colony counts 1:10 diluted agar at 20 degrees C which stabilized at a relatively high number and a significant alteration of the microflora.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2223522 TI - Occurrence and formation of biologically active amines in foods. AB - Attention is given to the toxicology of biogenic amines and their occurrence and formation in foods, with special emphasis on fermented foods. The role of the associated flora, the starter cultures used and their interaction is discussed. PMID- 2223523 TI - The effects of irradiation and temperature on the immunological activity of staphylococcal enterotoxin A. AB - The effects of irradiation and temperature on purified staphylococcal enterotoxin A were investigated using sensitive ELISA systems. Thermal inactivation of staphylococcal enterotoxin A in phosphate-buffered saline was considerably faster at temperatures of 60, 70, 115 and 121 degrees C than at 90 and 100 degrees C. In gelatin phosphate buffer, staphylococcal enterotoxin A was completely inactivated by irradiation at 8.0 kGy; in a 15% mince slurry, however, 27-37% of staphylococcal enterotoxin A remained at this level of irradiation. Even at a dose of 23.7 kGy, 16-26% residual staphylococcal enterotoxin A could still be detected. Generally, increasing the mince concentration increased the protection against the effect of irradiation on staphylococcal enterotoxin A. However, the protective effect of mince at a concentration of 50% was less than at a mince concentration of 30%. Both irradiation and heat processing of food should only be used in conjunction with good manufacturing practices to prevent proliferation of microorganisms and toxin productions. PMID- 2223525 TI - The presentation of research in clinical practice. PMID- 2223524 TI - Standard plate counts of drinking water: a comparison between incubation temperatures of 20 and 30 degrees C. AB - Standard plate counts of 5085 drinking water samples gathered in the Region of Basle were carried out over a period of 9 years (1977 to 1985). Two conditions of incubation were evaluated: 20 degrees C and 30 degrees C for 72 h. In ground water samples (3048 samples) colony forming units (cfu) at 30 degrees C were found to be higher than counts at 20 degrees C incubation, 45% of the samples contained greater than or equal to 2 cfu/ml at 30 degrees versus 35% at 20 degrees C. The median was 1 cfu/ml at both temperatures. In spring water samples (2036 samples) bacterial counts at 20 degrees C were found to be higher than counts at 30 degrees C incubation, 61% of the samples contained greater than 10 cfu/ml at 20 degrees C versus 51% at 30 degrees C. The median was 19 cfu/ml at 20 degrees C incubation versus 11 cfu/ml at 30 degrees C. These differences were statistically significant with p less than 0.001 (Wilcoxon matched-pairs signed rank test). No correlation was found between bacterial counts at 20 degrees C and bacterial counts at 30 degrees C, nor between bacterial counts and original water temperatures. It appears that incubation temperatures of 20 degrees C and 30 degrees C favor the growth of different populations of bacteria and temperature is not the only factor. However, from a practical point of view the use of only one incubation temperature seems to be justified for the purpose of judging the sanitary quality of drinking water. PMID- 2223526 TI - Displaced boxers' fractures: a simple and effective method of external splintage. AB - Forty patients with fractures of the fifth metacarpal neck (boxers' fractures) having a volar angulation of 30 degrees or more were treated by closed reduction and external immobilisation. A combination of malleable aluminium alloy splint and plaster of Paris cast was used. The results show a significant improvement in fracture angulation after reduction and at follow-up (3/5 weeks) using this form of external splintage. There were no complications. Our results compare favourably with those of other recently published series. We advocate the use of this method of treatment for these fractures with significant volar angulation. PMID- 2223527 TI - Topical anaesthesia with lignocaine-prilocaine cream (EMLA) for carbon dioxide treatment to the cervix--a pilot study. PMID- 2223528 TI - Hypertension in the elderly: a study of a combination of atenolol, hydrochlorothiazide and amiloride hydrochloride. AB - The anti-hypertensive effects of atenolol (Tenormin) 50 mg, a potassium-sparing diuretic (half-strength Moduretic) comprising hydrochlorothiazide 25 mg plus 2.5 mg amiloride hydrochloride, and the 'free' combination of atenolol and diuretic were compared in elderly hypertensive patients aged 60-79 years. After a four week run-in period on placebo, patients were randomly assigned, in a double-blind manner, to atenolol or diuretic treatment, each for four weeks. Thereafter patients were given the 'free' combination for a further four weeks and this treatment was continued for six months. Blood pressure and heart rate were measured after the patient had rested for five minutes supine and after two minutes standing. These blood pressure measurements were made at least 24 hours after the preceding dose using a Random Zero sphygmomanometer. Results from 26 of the 27 patients entered into the study showed an advantage for combination therapy combined with either atenolol or diuretic treatment alone. No significant difference was found between treatments in the frequency of supraventricular and ventricular ectopic beats occurring in six patients who underwent 24-hour ambulatory ECG monitoring. However, ectopic activity was reduced in some patients during beta-blocker treatment. Few adverse effects occurred with any treatment. Three patients withdrew during the placebo period and three withdrew while taking active treatment. This study has shown that the combination of atenolol, hydrochlorothiazide and amiloride hydrochloride is an effective, safe, well tolerated antihypertensive drug regimen when used once daily in elderly hypertensive patients. PMID- 2223529 TI - Medical eponyms updated: 1. Behcet's disease. PMID- 2223530 TI - Colonic bleeding may cause melaena. PMID- 2223531 TI - Pseudo-pyloric tumours. AB - Two infants presenting with vomiting were thought to have palpable pyloric tumours. At operation hypertrophic pyloric stenosis was not present, but other conditions causing duodenal obstruction were, and these required surgical treatment. The cases illustrate that other abnormalities may masquerade as pyloric stenosis. PMID- 2223532 TI - Mycotic aneurysm caused by group B streptococcus: a cautionary tale of management problems and a rare organism. AB - We report a case of mycotic aneurysm of the femoral artery which highlights the diagnostic features and management problems of the condition. Our patient required emergency ligation of the artery for life-threatening haemorrhage and subsequently his leg was not viable. The alternative treatment options of simple ligation and excision versus ligation, excision and immediate bypass grafting of the artery are discussed. The causative organism, beta-haemolytic group B streptococcus (S. Agalactiae), is an extremely rare cause of embolic mycotic aneurysm. This rarity is unexplained and is surprising since this organism is a well-known cause of infective endocarditis, which can be complicated by mycotic aneurysms. Mycotic aneurysms may become more common because of the rise of intravascular drug abuse, which combines the risk factors of vessel trauma, endocarditis and immunosuppression, notably from HIV infection. PMID- 2223533 TI - Apparent relapse of Legionella pneumonia. PMID- 2223534 TI - Acute appendicitis secondary to metastatic carcinoma of the breast. AB - A patient developing acute appendicitis and intestinal obstruction secondary to metastatic breast carcinoma is described. This rare occurrence may become more common with improved survival in cases of advanced breast malignancy. The intrinsic nature of malignant metastases in the appendix, with or without concurrent immunosuppressive chemotherapy, leads to a late presentation of appendicitis with a high incidence of perforation, associated with an increased mortality and morbidity. It is suggested that appendicectomy should be undertaken as a routine in patients with carcinoma of the breast when oophorectomy or laparotomy is to be performed. PMID- 2223535 TI - Polymyositis presenting with dyspnoea, greatly raised muscle enzymes, but no apparent muscular weakness. PMID- 2223536 TI - Thyrotoxicosis in a patient with Addison's disease. AB - We report the case of a patient who suffered recurrent episodes of hypoadrenal crisis, despite conventional replacement therapy for Addison's disease. She was found to have hyperthyroidism and after this was treated, she had no further relapse. Thyrotoxicosis should be considered when patients taking replacement therapy for Addison's disease present in hypoadrenal crisis. PMID- 2223537 TI - Femoral hernia in children. AB - Femoral hernia is rare in children. Unfamiliarity with the occurrence of this condition may lead to incorrect diagnosis and delayed treatment. This mistake can be obviated by careful clinical examination. PMID- 2223539 TI - Selective use of arteriography in the assessment of aortic aneurysm repair. AB - Routine preoperative arteriography is advocated by many vascular surgeons before abdominal aortic aneurysm repair. We have used a selective approach based on the facts that arteriography is expensive, time-consuming, potentially hazardous, and often unwarranted. Based on preoperative indications, arteriography was used selectively in 41 of 100 consecutive patients prior to abdominal aortic aneurysmectomy. Many patients had more than one indication. A total of 82 specific indications were recognized. The most frequent indications were diminished lower extremity pulses (24), claudication (20), severe coronary artery disease (11), cerebrovascular disease (7), prior arterial reconstruction (8), hypertension in patients 60 years of age or less (5), evidence of other aneurysms (4), major renal anomaly (1), blue toe syndrome (1), and thoracic aneurysm (1). The 41 arteriograms produced 125 specific arteriographic abnormalities with an average of three per study. The most arteriographic abnormalities were in those patients with claudication and the least for those with hypertension. The arteriogram revealed information that would not have been obvious at operation, nor would it have led to operative procedure modification in only 10 patients. In the 59 patients not having arteriography, three had intraoperative findings which demanded a modification of the operative procedure. Thus, in only 13 patients was arteriography definitely useful. Presumably it was not indicated in the other 87. By comparing the cases in which the operation was modified with the presence of a specific indication, we have developed a predictability index as a guide for performing arteriography. Multiple indications increased the likelihood of operation modification only if four or more indications were present. PMID- 2223538 TI - Vascular injuries in the urban battleground: experience at a metropolitan trauma center. AB - The increasing frequency and severity of urban violence and vehicular injuries have brought with them a rise in the number of complex vascular injuries. To examine the cause, incidence, management, and outcome of this problem, we created a vascular trauma registry which includes all such cases treated at a Level I metropolitan trauma center over the past nine years. This constitutes a summary report of that registry. During the period 1979-1988, 411 patients (355 men, 56 women) with 478 vascular injuries were treated. There were 18 deaths (4%). Primary diagnosis was grouped by anatomic region: (1) head and neck vessels, 62 (15%); (2) thoracic, 39 (10%); (3) abdominal and pelvic, 63 (15%); (4) upper extremity, 161 (39%); and (5) lower extremity, 86 (21%). Surgery was required in 241 cases (60%). Operative techniques consisted of ligation or resection in 26 (12%) and direct repair in 212 (88%). Associated procedures included: (1) laparotomy (n = 83); (2) craniotomy (n = 4); (3) thoracotomy (n = 49); (4) orthopedic procedures (n = 118); and (5) peripheral neurological repair (n = 70). Mechanisms of injury were: (1) gunshot wounds (32%); (2) stab wounds (45%); (3) motor vehicle accidents (18%); (4) fall (3%); and (5) other mechanisms (2%). We conclude: (1) vascular injuries were found frequently in the severely injured patient; (2) multiple vascular repairs were required in a significant proportion of these patients; and (3) outcome is dependent more upon associated trauma than on the vascular injuries themselves. PMID- 2223540 TI - Endovascular occlusive intervention in the management of trauma. AB - This report summarizes a 10-year experience (1978-1987) in a metropolitan hospital with 102 patients sustaining a variety of complex or inaccessible vascular injuries. Management included the application of occlusive interventional arteriographic techniques. Regional injuries included head and neck (56%), trunk (13%), and extremity (32%). Techniques of vascular occlusion were often performed in conjunction with the initial arteriographic evaluation and were comprised of particulate embolization (42%), placement of mechanical devices (36%), or tissue adhesives (1%), or a combination (21%). There were no deaths in this series and the only complications included four cases of dislodgement of the occlusive agent. We demonstrate that endovascular occlusion is a useful, safe and efficacious procedure in selected patients with complex, inaccessible or life-threatening vascular trauma. PMID- 2223541 TI - Doppler ultrasound in aortic dissections: a study of cephalic and peripheral arteries. AB - We investigated the role of continuous-wave Doppler ultrasound in predicting the presence of an aortic dissection prospectively in 28 patients whose diagnosis was confirmed either by arteriography or surgery (26 cases) or at autopsy (two cases). We hypothesized that dissections, by creating two channels for flow, would produce velocity disturbances detectable in accessible arteries such as the carotid, brachial, and femoral arteries. Of the 28 patients, 20 had Type I, two Type II, and six Type III dissections. Two abnormalities of the Doppler signals were found: in 18 of Type I dissections, notching was found in the systolic upslope of the velocity tracing from those arteries that were either involved in or distal to the dissection sites. Notching was much less frequent for Type II and III dissections: only one patient with Type II and two patients with Type III dissections showed notching. In addition diastolic backflow with marked aortic valvular insufficiency was present. Notching in brachiocephalic artery continuous wave Doppler signals appears to have a high positive predictive value for Type I dissections. PMID- 2223543 TI - Long-term survival in patients undergoing resection of abdominal aortic aneurysm. AB - The long-term survival of patients undergoing abdominal aortic aneurysm surgery is presented. Three-hundred and thirty-eight patients who presented with elective, urgent, or emergency abdominal aortic aneurysms, have been followed retrospectively for five years. We found no statistical difference in the long term survival in these three groups of patients. As expected patients who had successful operation survived better than patients who were not offered surgery because of their poor medical condition. Interestingly, advancing years, history of myocardial infarction or hypertension did not significantly influence long term survival. PMID- 2223542 TI - Functional status of the deep venous system after an episode of deep venous thrombosis. AB - An episode of deep venous thrombosis is often followed by the opening of collaterals, fibrinolysis, recanalization and valvular dysfunction. The effect of these processes on the peak flow velocity in the superficial femoral and popliteal veins after simulated contraction of the calf muscles was tested in a group of normal subjects and three groups of patients who had deep venous thrombosis. There were 12 patients followed less than two years with no skin changes. The second group consisted of 12 patients followed for 8-15 years without ulceration. The third group of 12 patients had active or healed ulcers. The peak flow velocity in the superficial femoral and popliteal veins was assessed by rapidly inflating cuffs about the calf and ankle to 100 mmHg. The velocities generated by cuff compression were lower in patients than in normal subjects. This was particularly true in the superficial femoral vein. This change in velocity may be secondary to incomplete recanalization with resulting stenosis or valvular incompetence in the calf. PMID- 2223544 TI - Accuracy of B-mode ultrasonography in detecting carotid plaque hemorrhage and ulceration. AB - A prospective study comparing the accuracy of B-mode ultrasound with evaluation of gross appearance in detecting plaque hemorrhage and ulceration is reported. Ultrasonography was performed on 78 vessels in 66 patients undergoing carotid endarterectomy. Carotid bifurcation atheroma were classified ultrasonographically as smooth, irregular, or ulcerated. Sonolucent areas were considered to be plaque hemorrhage. Analysis of carotid plaques removed at operation included macroscopic and microscopic findings. Duplex Doppler was only 44% sensitive but 78% specific for plaque hemorrhage. If all irregular atheroma were considered ulcerated, the sensitivity of Duplex Doppler was 81% with specificity only 33%. If only lesions with a clearly visualized crater were considered ulcerated, B-mode ultrasound was 85% specific but only 17% sensitive. False B-mode ultrasound diagnoses of ulceration were mainly due to culs-de-sac or pits in fibrotic plaque that looked like ulcers. Ulceration was not noticed on B-mode when there was a two dimensional problem or calcification with shadowing. False B-mode diagnoses of plaque hemorrhage were due to atheromatous debris, ulcerated plaque hemorrhage, or calcification. Problems still exist in the B-mode ultrasound diagnosis of carotid plaque hemorrhage and ulceration. PMID- 2223545 TI - Renal artery revascularization with polytetrafluoroethylene bypass graft. AB - Between January 1979 and December 1986, a total of 74 renal revascularizations were performed in 68 patients using the reinforced expanded polytetrafluoroethylene prosthetic graft. These 74 revascularizations represent 29% of 251 surgical renal revascularizations performed during the same period of time. Eight patients had a total of nine revascularizations in the emergency setting (group I) for ruptured suprarenal aneurysm or acute thrombosis of the renal arteries. Only one patient survived and six years later, his anatomic and functional results are satisfactory. Sixty-five revascularizations were performed electively in 60 patients (group II). This group consisted of 19 renal revascularizations alone, and 46 combined aortic and renal revascularizations. One patient died of respiratory complications two months after operation after his thoracoabdominal aneurysm was cured. Early repeat postoperative arteriography showed that six reconstructions had occluded (three major renal arteries, three polar arteries). One patient was lost to follow-up. The remaining patients were followed for a mean of 41 months. Follow-up arteriograms obtained during 1987 showed that there were two late occlusions and two distal anastomotic stenoses. Actuarial patency was 85 +/- 10% at 72 months. Polytetrafluoroethylene prosthetic grafts constitute a reliable material for renal revascularization and combined aortic and renal reconstruction in certain anatomic conditions. PMID- 2223546 TI - Routine exercise testing to detect coronary artery disease in patients with atherosclerotic vascular disease. AB - The ability of patients with peripheral vascular disease to perform exercise studies on a conventional treadmill is often hampered by claudication, amputation, ischemic ulceration or rest pain. This study was undertaken to investigate the use of the arm ergometer in these patients. Eighty-three patients admitted with peripheral vascular or carotid artery disease were subjected to electrocardiographic-monitored exercise testing, using both the arm ergometer and conventional treadmill, where possible. Coronary arteriography was performed consecutively on 32 of these patients to establish a control group from which the sensitivity, specificity and predictive accuracy of both methods of exercise testing could be calculated. Nineteen of the 70 arm ergometry tests and 22 of the 48 treadmill tests were positive. Nineteen of the patients with a positive test using either of the methods were asymptomatic for cardiac disease. All five patients who developed cardiac events during surgery had positive exercise tests, preoperatively. The sensitivity of arm ergometry in detecting coronary artery disease was 45.5% and the specificity 100%, while the figures for treadmill testing were 82.4% and 83.3%, respectively. The combined sensitivity for the two tests was 81.8% and the specificity 87.5%. Using a combination of these two tests thus provided a highly specific and adequately sensitive means of detecting the presence of coronary artery disease in patients presenting for peripheral vascular surgery. PMID- 2223547 TI - The silent brain infarct before and after carotid surgery. AB - Routine computed tomography was prospectively performed pre- and postoperatively in 114 consecutive patients undergoing a total of 131 procedures on the carotid artery. Hemispheric cerebral infarction was found preoperatively in three of the 16 hemispheres corresponding to symptomatic lesions (19%), in 18 of 109 hemispheres corresponding to transient ischemic attacks (16.5%), and in one of four hemispheres corresponding to lesions responsible for a fixed cerebral vascular accident (25%). Two surgical procedures (1.5%) were complicated by early cerebral infarctions as detected on postoperative computed tomographic scan. These complications resulted in death in one case, and left the patient with major sequelae in the other. Five procedures (3.8%) were complicated by transient ischemic attacks, three of which were associated with minimal cerebral infarctions visible on computed tomographic scan. Neurologic status was unchanged after 124 (94.6%) procedures, whereas four of these procedures were complicated by silent brain infarctions as visualized on postoperative computed tomographic scans (3.1%). This study confirms that existing pre- and postoperative neurologic classifications are far from perfect and that surgery is rarely responsible for cerebral infarction. Carotid surgery should no longer be performed without obtaining pre- and postoperative computed tomographic scans. PMID- 2223548 TI - Surgical treatment of complete renal artery occlusion in pediatric patients. AB - Two children, 8 and 11 years old, presented with severe hypertension secondary to unilateral and bilateral total occlusion of the renal arteries, respectively. The 11-year-old developed sudden anuria requiring hemodialysis. Successful surgical reconstruction allowed recovery of renal function and normal blood pressure in both patients. Routine blood pressure control in the pediatric patient population, high clinical awareness, and judicious use of arteriography, provide the best chance for early diagnosis of renovascular disease. Surgical revascularization or transluminal angioplasty are the treatment modalities of choice in appropriately selected cases of renal artery stenosis. When total occlusion occurs, retrieval or preservation of renal function can be successfully achieved by direct surgical intervention. PMID- 2223549 TI - The use of internal jugular vein as interposition graft for femoral vein reconstruction following traumatic venous injury: a useful approach in selected cases. AB - Complex venous injuries remain a controversial and interesting challenge to the vascular and trauma surgeon. Data from the Vietnam Vascular Registry, combined with experience from recent civilian series, seem to indicate that the best results are obtained when venous repair is undertaken. This is especially true of combined arterial and venous injury where compromised venous outflow may lead to limb loss in spite of patent arterial reconstruction. The larger size of veins, however, has required the construction of complex and time-consuming panel and spiral-vein grafts. This makes them far from ideal in the trauma treatment setting, where minimization of blood loss and operating room time are high priorities. We present a case of combined injury to both femoral artery and vein, where the femoral vein injury was repaired using autologous internal jugular vein as interposition graft while the arterial injury was repaired with autologous saphenous vein from the opposite limb. The avoidance of prosthetics, ease of harvest, size match, and little associated morbidity all make a strong case for use of the internal jugular vein where speedy reconstruction of large venous conduits is indicated. PMID- 2223551 TI - Acute visceral ischemia secondary to aortic graft occlusion. AB - This report describes a case of acute visceral ischemia precipitated by aortic graft occlusion. The importance of recognizing and treating visceral artery lesions at the time of aortic reconstruction is emphasized. PMID- 2223550 TI - Bilateral congenital aplasia of the deep femoral arteries. AB - A patient with bilateral congenital aplasia of the deep femoral arteries is described. The condition was accompanied by aneurysms of the popliteal arteries. Besides the academic interest of such an anatomical rarity, the abnormality is of clinical importance insofar as acute ischemia of the extremity may occur in the presence of superficial femoral artery occlusion. PMID- 2223552 TI - Rupture of a superior mesenteric artery aneurysm in a child. AB - A 13-year-old child presented with a ruptured aneurysm of the trunk of the superior mesenteric artery most likely due to incipient fibromuscular disease localized in the adventitia. The aneurysm was resected and replaced by an autologous saphenous vein graft. The postoperative course was uneventful. Diagnosis and operative strategy are discussed. PMID- 2223553 TI - Congenital anomalies of the external iliac artery: case report and review of the literature. AB - Routine arteriograms obtained during work-up for occlusive arterial disease of the lower limbs disclosed a rare congenital anomaly in a 47-year-old man. The common femoral artery arose directly from a pelvic artery which followed the normal course of the internal iliac artery. Congenital anomalies involving the external iliac artery can be classified into three groups: (1) anomalies of origin or course which are in fact anatomic curiosities; (2) hypoplasia or atresia coexisting with persistent sciatic artery; and, (3) isolated hypoplasia or atresia which can occasionally cause chronic ischemia of the lower limbs. The anomaly reported herein can be classified either as agenesia or abnormal course of the external iliac artery. PMID- 2223555 TI - Expression of a p55 interleukin-2 receptor-like molecule on corneal epithelial cells. AB - We observed a molecule on the surface of mouse corneal epithelial cells that is similar or identical to the p55 subunit of the high affinity interleukin-2 receptor (p55 IL-2R). The presence of this molecule in normal corneas was demonstrated by immunoperoxidase staining with a monoclonal antibody (mAb) specific for p55 IL-2R (7D4). Staining was observed only in the corneal epithelium. The staining intensity was greatest in the central cornea, becoming weaker toward the corneal scleral limbus, and was very weak or absent in the conjunctival epithelium. Other ocular tissues were not stained. Epithelial cells grown in tissue culture from corneal explants retained expression of the molecule recognized by 7D4 as demonstrated by immunoperoxidase staining. Western Blot analysis of an extract of corneal epithelium demonstrated the presence of a 55 kD protein that reacted with 7D4. Our findings suggest that a molecule similar both antigenically and in molecular size to the p55 IL-2R subunit is constitutively produced by corneal epithelial cells. PMID- 2223554 TI - A novel microwell indirect immunofluorescence assay to detect antibodies against islet cell surface antigens in insulin-dependent diabetes mellitus. AB - End-point titers of islet cell surface antibodies (ICSA) were determined in 144 patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM), 98 siblings to such patients, and 188 controls using a microwell indirect immunofluorescence assay with an insulin-producing cell line of Syrian hamster origin. The prevalence of ICSA of a titer equal to or greater than 1:4 was 33% (p less than 0.001) in IDDM patients and 15% (p less than 0.01) in siblings, compared to 5% among the controls. In patients under 15 years of age at clinical onset, the prevalence of ICSA was 43% (37/77), which was higher than the 30% (20/67) found in patients older than 15 years at onset (p less than 0.05). The ICSA titer at the time of diagnosis varied between 1:4 and 1:32; however, 43% (23/53) of ICSA positive IDDM patients had a titer equal to or greater than 1:8. Although gender did not affect ICSA prevalence, 56% (15/27) of the female IDDM patients had ICSA titers exceeding 1:8 which was higher than 30% (8/26) among male patients (p less than 0.05). These results confirm that IDDM patients have a high prevalence of ICSA and that this convenient, high capacity immunofluorescence assay allows studies of large numbers of serum samples. The cell-specific reaction following absorption should also allow the islet cell surface antigens to be characterized. PMID- 2223556 TI - Mast cells in the murine oral mucosa are of the connective tissue-type. AB - The distribution, histochemistry, and functional properties of oral (cheeks, soft palate, and tongue) mast cells (MC) was compared to those of peritoneal, cutaneous, and intestinal MC. The ultrastructure of oral MC was also studied. Fresh tissue and peritoneal cells were fixed either in absolute ethanol or in periodate lysine 2% paraformaldehyde and embedded in paraffin. For electron microscopy, specimens were fixed in 1% glutaraldehyde in formol and embedded in epon. Serial paraffin sections were stained with Giemsa, toluidine blue (0.5% and 0.005%), astra blue/safranin, alcian blue/safranin, berberine sulfate, safranin alone, and fluorescein-labelled avidin to determine the staining properties, incidence, and distribution of both connective tissue-type MC and mucosal-type MC at these sites. Oral, peritoneal, and cutaneous MC granules stained positively with Giemsa, toluidine blue (0.5 and 0.005%), alcian blue, astra blue, berberine sulfate, safranin used alone, and avidin-FITC, but failed to stain with safranin when used in sequence with alcian blue or astra blue. Intestinal MC stained with the same dyes as oral MC except for 0.005% toluidine blue, berberine sulfate, and safranin. Oral and lingual MC are located in the deep lamina propria, around blood vessels and salivary secretory ducts, in close association with nerve endings, and between muscle fibers. In the cheeks and soft palate, but rarely in the tongue, MC were also found around and between glandular acini. MC constitute a predominant immune component in oral tissues, being more numerous in the soft palate and cheek-labial junction (4800/mm3) and in the tongue (4000/mm3), than in the duodenal mucosa (2650/mm3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223557 TI - Inhibition of DNA synthesis in human peripheral and lamina propria lymphocytes by 5-aminosalicylic acid and hydrocortisone. AB - 5-Aminosalicylic acid (5-ASA) and hydrocortisone (HC) have potent antiinflammatory activity, and are commonly used in the treatment of patients with inflammatory bowel disease. Both agents have been reported to modulate immune function in human and animal models. We investigated the effect of 5-ASA and HC on cell proliferation of normal human peripheral blood lymphocytes (PBL) and normal colonic lamina propria lymphocytes (LPL). Both 5-ASA (0.01-4 mM) and HC (0.01-10 microM) significantly inhibited 3H-thymidine incorporation (Thd) into PBL and LPL in a dose dependent manner. Maximal inhibition occurred with the highest concentration tested of both 5-ASA and HC. We found a significantly greater inhibition of DNA synthesis for 5-ASA (4 mM) upon LPL vs. PBL (94 vs. 32%, p less than 0.001). However, DNA synthesis inhibition by HC was similar in PBL and LPL. The profoundly greater inhibitory effect of 5-ASA upon LPL suggests a specific modulation of the mucosal immune system. PMID- 2223560 TI - Surveillance of tetanus, 1987 and 1988. PMID- 2223558 TI - Compartmentalization and kinetics of lymphoid cells in the lung. PMID- 2223559 TI - Ultrastructural study of liposome uptake by M cells of rat Peyer's patch: an oral vaccine system for delivery of purified antigen. AB - Liposomes (phospholipid artificial membrane vesicles) have been used in targeted drug delivery and recently in the development of oral vaccines using purified soluble antigens for the induction of mucosal immune responses. Although the mechanisms by which liposomes promote the induction of responses to soluble antigens have not been clearly shown, it has been suggested that these vesicles, when given orally, are taken up by M cells for delivery of antigen to underlying lymphoid cells of the Peyer's patch. This study investigated in vivo the uptake of liposomes by cells of Peyer's patch. Following exposure of surgically constricted segments of rat small intestine to small unilamellar liposomes or gold-labelled solid core liposomes, Peyer's patches were removed, fixed, and processed for examination by transmission electron microscopy. Sections of Peyer's patch from experimental animals showed M cells with endocytic vesicles containing liposomes. Vesicles containing liposomes were also observed between M cells and lymphoid cells. These results indicate that intact liposomes are endocytosed by M cells and provide evidence for a possible mechanism by which M cells deliver antigen to lymphoid cells in the Peyer's patch. These findings support the potential usefulness of liposomes in oral vaccine development. PMID- 2223561 TI - Measles. Surveillance in England and Wales, 1960-1989. PMID- 2223562 TI - Expanded programme on immunization. Neonatal tetanus survey. PMID- 2223563 TI - Injury prevention. Cost of injury--a report to Congress, 1989. PMID- 2223564 TI - Acquired immunodeficiency syndrome (AIDS)--data as at 31 August 1990. PMID- 2223565 TI - Meningococcal disease. Situation from 1983 to 1989. PMID- 2223566 TI - Acquired immunodeficiency syndrome (AIDS)--data as at 30 September 1990. PMID- 2223567 TI - Epidemiological surveillance. Development of an international sentinel network of general practitioners (Eurosentinel). PMID- 2223568 TI - Sexually transmitted diseases. Gonorrhoeae. PMID- 2223570 TI - Malnutrition. PMID- 2223569 TI - Surveillance of sexually transmitted diseases, 1989. PMID- 2223571 TI - The Cotswolds report on the investigation and staging of Hodgkin's disease. PMID- 2223572 TI - Modification of the 31P magnetic resonance spectra of a rat tumour using vasodilators and its relationship to hypotension. AB - The effects of different doses of hydralazine and prostacyclin on the 31P magnetic resonance spectra of the LBDS1 fibrosarcoma were investigated and related to their effects on mean arterial blood pressure (MABP) and heart rate. The effect of reducing MABP by bleeding the animals, via the tail artery, was also investigated. Tumour spectral changes following high dose drug treatment (an increase in inorganic phosphate, a reduction in nucleotide triphosphates and a reduction in pH) were consistent with nutrient deprivation. These changes were dose dependent. Changes in MABP and heart rate were consistent with vasodilatation in normal tissues. However, for the same fall in MABP, hydralazine produced a greater rise in tumour inorganic phosphate (Pi) and a greater fall in tumour pH than did prostacyclin. Controlled bleeding was effective in reducing MABP. It also reduced tumour pH but had no significant effect on tumour Pi. The clinical application of the two drugs for reducing tumour blood flow and pH for therapy is likely to be limited by the large degree of hypotension necessary to produce an effect. The differential effect of the two drugs for the same fall in MABP may be related to different degrees of direct tumour vasodilatation or to a direct effect of hydralazine on tumour energy metabolism. The observation that controlled bleeding does not change tumour Pi is further evidence indicating that the degree of arterial hypotension is not the sole factor in determining tumour energy status. PMID- 2223573 TI - The role of colon fibroblasts in malignant large bowel obstruction--an experimental in vitro model. AB - The mechanism of bowel obstruction in colorectal cancer is likely to involve interactions between tumour cells, host fibroblasts and the extracellular matrix. The role of fibroblast-mediated matrix reorganisation in malignant structures of the large bowel was examined in an in vitro collagen matrix model in which tumour cells and fibroblasts were cultured under serum-free conditions. Colon cancer cells secreted a factor(s) which enhanced the ability of colon fibroblasts to contrast a collagen matrix without an associated mitogenic response by the fibroblasts. Within uncontracted collagen gels marked elongation of fibroblast cell processes was observed in the presence of the tumour-derived factor(s). We propose that matrix reorganisation by host fibroblasts in the wall of the human colon is responsible, at least in part, for malignant large bowel obstruction. PMID- 2223574 TI - Radioimmunotargeting of human tumour cells in immunocompetent animals. AB - A tumour model system is reported that for many purposes may be an alternative to xenografted nude mice. The model allows immunotargeting of human tumour cells in immunocompetent animals. The target cells are contained in i.p. diffusion chambers (DC) with micropore membrane walls that are permeable to molecules, including the cell specific monoclonal antibodies (MoAb), but impermeable to cells. Thus, the tumour cells are protected from the host immunocompetent cells. In the work here presented the model was tested in immunocompetent mice and pigs, with tumour cells and antibody preparations that had demonstrated specific targeting in the nude mouse xenograft model. Hence, the DC were filled with cells from the human cell lines Hep-2 (expressing placental alkaline phosphatase, PLALP), or OHS (a sarcoma cell line), and the MoAb preparations injected i.v. were a 125I-labelled Fab fragment of the PLALP specific antibody H7, or a 125I labelled F(ab')2 fragment of the sarcoma specific antibody TP-1. Specific targeting of the human tumour cells was demonstrated in both mice and pigs. The target: blood ratios were comparable in the two species, reaching a maximum of about 15 after 24 h with the Fab preparation, and a ratio of 25 after 72 h with the F(ab')2. The target uptake relative to injected dose was lower in pigs than in mice, but the difference between the two species was smaller than expected, presumably due to a slower antibody clearance in the pigs than in the mice. An artificial cell targeting system like this has several advantages in the search for solutions to many of the fundamental problems experienced in immunotargeting. Firstly, parallel binding experiments can be carried out in vitro with the same target. Because in vitro results are only influenced by the diffusion into the DC and the immunological binding characteristics of the antibodies, targeting differences between antibody preparations due to these factors can then be distinguished from differences due to pharmacokinetical properties. Secondly, the animals can be implanted with any type and number of target cells, or with antigen negative control cells. Thirdly, and perhaps most important, the system opens a possibility for evaluation of the murine MoAb in xenogenic species, and this may predict the clinical targeting potential better than experiments on mice. PMID- 2223575 TI - Production and response of a human prostatic cancer line to transforming growth factor-like molecules. AB - Serum-free media conditioned by the androgen insensitive human prostate cancer cell line DU145 showed immunological transforming growth factor-alpha (TGF alpha) activity, as well as competing activity in epidermal growth factor (EGF) radioreceptor assays (RRA). Furthermore, there were factors in the conditioned media which inhibited and stimulated DNA synthesis by DU145 cells in a dose dependent fashion. Fractionation of the concentrated conditioned media by reverse phase high performance liquid chromatography revealed several peaks containing EGF-like competitive activity only one of which demonstrated TGF alpha activity. However, none of the peaks corresponded to immunoreactive EGF. Measurement of EGF receptors on DU145 cells by competition and saturation analysis revealed high levels of receptors (mean +/- s.d. = 2.5 +/- 1 x 10(5) surface receptors per cell) which were of high affinity (Kd +/- s.d. = 1.0 +/- 0.5 nmol l-1). Although DU145 cells express high levels of EGF receptors, DNA synthesis was only minimally affected by exogenous EGF and TGF alpha. PMID- 2223576 TI - The polyoxyethylene castor oil Cremophor EL modifies multidrug resistance. PMID- 2223577 TI - HAB-1, a new heteromyeloma for continuous production of human monoclonal antibodies. AB - To obtain suitable cell lines for the immortalisation of human lymphocytes, we constructed a heteromyeloma between the murine myeloma Ag8 and human lymphocytes from a highly malignant polymorphic, centroblastic B-cell lymphoma. The thioguanine-resistant and HAT-sensitive heteromyeloma HAB-1 neither secretes nor contains cytoplasmatic immunoglobulins, the cells being EBV negative but positively stained for HLA-BC and the human proliferation marker Ki-67. The karyotype consists of about 50 murine and 20 human chromosomes. The HAB-1 cells grow in suspension and have a doubling rate of about 25-30 h. In fusion experiments with spleen cells from stomach carcinoma patients HAB-1 cells show a 5-7 times higher fusion efficiency than murine Ag8 cells or another heteromyeloma SPM4-0 and give stable antibody producing products. The cell line will be made available to interested scientists. PMID- 2223578 TI - Glutathione S-transferase (placental) as a marker of transformation in the human cervix uteri: an immunohistochemical study. AB - Using an indirect immunohistochemical technique on paraffin sections, employing a polyclonal antibody to the acidic (placental) form of glutathione-S-transferase (GST), we have evaluated cytoplasmic and nuclear staining in a series of 67 cervical biopsies including normal non neoplastic tissue, immature squamous metaplasia, all grades of cervical intraepithelial neoplasia (CIN) and invasive carcinomas of keratinising and non-keratinising types. No differences in cytoplasmic staining between the varied lesions studied were seen. However, there were marked differences in nuclear staining. While normal non-neoplastic stratified squamous epithelium showed weak staining of the lower one-third of the epithelium only, in immature squamous metaplasia and in all grades of CIN there was intense nuclear staining in all layers of the epithelium. Invasive carcinomas showed generally less intense nuclear staining than CIN lesions. Endocervical cell nuclei also showed intense nuclear staining. These findings indicate that GST is of limited use as a marker of transformation in the human cervix uteri. PMID- 2223579 TI - Is group psychotherapy feasible for oncology outpatients attenders selected on the basis of psychological morbidity? AB - Of 120 consecutive attenders at an oncology outpatients department, 108 were screened for psychological symptoms using the Hospital Anxiety and Depression Scale (Zigmond & Snaith, 1983). Thirty-nine patients had significant scores indicating moderate anxiety and/or depression. We felt that this warranted an offer of group psychotherapy in the belief that sharing issues and exploring personal concerns may alleviate some of the experienced psychological distress. Only 10 patients consented to and were able to attend this group, with which five patients persisted. Thus in this group of patients with advanced cancer group psychotherapy was applicable only to a limited number of selected patients. The nature of this study and the size of the population markedly limited our ability to comment on the usefulness of group psychotherapy. Many patients, particularly the most severely psychologically distressed, continued to require other forms of support, particularly domiciliary individual therapy. PMID- 2223580 TI - Sex hormones in women in rural China and in Britain. AB - Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group. PMID- 2223581 TI - Intrathecal administration of 131I radiolabelled monoclonal antibody as a treatment for neoplastic meningitis. AB - Fifteen patients with neoplastic meningitis received a single intrathecal injection of between 11 and 60 mCi of a 131I radiolabelled monoclonal antibody (MoAb), chosen for its immunoreactivity to tumour. Major toxicity was manifest as nausea, vomiting and headache (7/15 patients), reversible bone marrow suppression (3/8 patients) and seizures (2/15 patients). Nine patients were evaluable for either a tumour or clinical response. Six of these demonstrated an event-free response that was maintained for periods of between 7 and 26 months. PMID- 2223583 TI - The first 2 years of the Gambian National Cancer Registry. AB - We describe the creation, and the first 2 years experience, of the Gambian National Cancer Registry. The major problems involved in the creation of such a registry in a developing country are discussed. The data accumulated show a low overall rate of cancer incidence compared to more developed parts of the world and indicate that the prevalent cancers, hepatoma, carcinoma of the cervix and lymphoma, are likely to be due to infectious agents. It is hoped that immunisation of children under one year against hepatitis B will drastically reduce the incidence of hepatocellular carcinoma. PMID- 2223582 TI - Prolactin receptor does not correlate with oestrogen and progesterone receptors in primary breast cancer and lacks prognostic significance. Ten year results of the Naples adjuvant (GUN) study. AB - The correlation between prolactin (PRLR) and oestrogen (ER) or progesterone receptors (PgR) in breast cancer and a possible prognostic significance of PRLR at 10 year follow-up have been investigated in the Naples (GUN) adjuvant trial. A total of 308 pre- and post-menopausal patients with early breast cancer, who entered the trial from 1 February 1978 to 31 December 1983, received randomly Tamoxifen (TM), 30 mg per die for 2 years, or no therapy. PRLR status was known in 229 (74.3%) patients. Values of specific binding less than 1% were considered negative. PRLR was positive in 75/229 (32.8%). ER was assayed in 210/229 (91.7%) patients and PgR in 188/229 (82.1%). No significant correlation, by the Spearman test, was found between PRLR and ER or PgR, while ER status was highly interrelated with PgR status. By the Cox model no evidence of an independent prognostic role of PRLR on disease-free survival (DFS) was observed, nor an interaction between PRLR and adjuvant treatment with TM was found. PMID- 2223584 TI - Vitamin A, vitamin E and the risk of cervical intraepithelial neoplasia. PMID- 2223585 TI - Immunohistochemical analysis of the cerebrospinal fluid for carcinomatous and lymphomatous leptomeningitis. AB - To evaluate the sensitivity and specificity of immunohistochemical analysis in relation to the standard cytological examination of the cerebrospinal fluid (CSF) in patients with either a solid tumour or a haematological malignancy and possible leptomeningeal disease, 68 CSF-samples derived from 68 patients were examined. The sensitivity of immunohistochemical analysis was 0.54 and its specificity 0.98. Only one patient had a positive immunohistochemistry and a negative cytology. The gain of adding immunohistochemistry to cytology is nearly 8%. It is concluded that immunohistochemistry should not be used as a screening test for leptomeningeal disease in patients with cancer. PMID- 2223586 TI - Survival of intravenous chemotherapy infusion sites. AB - Factors associated with the failure of intravenous infusions due to phlebitis and extravasation were studied with 218 infusions delivering cytotoxic drugs. The survival rate of these infusions was not significantly different from that of 56 non-cytotoxic infusions in oncology patients. Although survival analysis indicated that cisplatin was associated with longer survival, this was probably an artifact caused by this drug usually being preceded by 24 h prehydration. Multivariate analysis indicated that etoposide was the only drug associated with decreased infusion survival and that bleomycin, cyclophosphamide, doxorubicin, ifosphamide, methotrexate, treosulphan and 5-fluorouracil had no significant effects. Also age of patient, infusion site and flow rate had no effects but survival was shorter in women. Follow-up indicated that failure of an infusion tended to result in loss of the vein. It is suggested that irritancy of the large volumes of intravenous fluids given to hydrate these patients rather than the cytotoxic drugs was the main factor reducing the survival of these infusions. PMID- 2223587 TI - Thymidine kinase in breast cancer. AB - The enzyme thymidine kinase is associated with DNA synthesis. Thymidine kinase serum levels were studied in normal controls (n = 20), patients with primary breast cancer (n = 60), patients with systemic breast cancer (n = 20) and as a non-cancer disease control group in patients with inflammatory gastrointestinal disorders (n = 20). Comparison of pretreatment values in the cancer patients with the normal controls showed a significant difference between the three groups in relation to stage of disease: mean values 4.22 (+/- 1.08), 6.22 (+/- 2.24) and 9.79 (+/- 7.56) pmol ml-1 h-1 for normal controls, operable breast cancer and systemic breast cancer respectively (P less than 0.005; analysis of variance). Patients with systemic breast cancer had a significantly elevated serum thymidine kinase level compared to controls (P less than 0.01) and patients with primary operable cancer (P less than 0.05). Patients with primary operable cancer had significantly higher serum thymidine kinase levels over normal controls (P less than 0.01). Mean serum TK in patients with inflammatory gastrointestinal diseases was similar to normal controls but significantly less than both patients with primary operable breast cancer and patients with systemic breast cancer. Twenty patients with operable breast cancer were followed up after primary surgery by serial 3-monthly thymidine kinase levels in the disease free interval. Four patients have developed systemic recurrence with a rise in the mean thymidine kinase value to 14.3 pmol ml-1 h-1. Ten patients with advanced breast cancer had serial thymidine kinase levels measured 2-monthly during the first 6 months of primary hormone therapy. The serum values fell in all five responders (mean 9.12 4.78 pmol ml-1 h-1) and rose in all five progressors (mean 8.62-38.5 pmol ml-1 h 1). Serum thymidine kinase reflects stage of disease in breast cancer. Serial thymidine kinase levels in patients with systemic breast cancer reflected response to systemic therapy. PMID- 2223588 TI - Elevated CA125 levels in patients with metastatic breast carcinoma. PMID- 2223589 TI - Using mathematical models to estimate drug resistance and treatment efficacy via CT scan measurements of tumour volume. AB - A previously described mathematical model designed to evaluate resistance and tumour-kill for individual patients, and to predict changing tumour sizes, has been applied to patients with small cell lung cancer. The model requires tumour volume measurements, and these were obtained via computed tomography scans of the chest. The model fitted the data well, and was able to predict later tumour volumes using earlier ones, as well as suggesting times at which to change or abandon treatment for individual patients. The model gave estimates for resistance and tumour-kill which may provide additional useful outcome measures for clinical trials, and help in the design of future studies. PMID- 2223590 TI - Serum CA125 level is a good prognostic indicator in lung cancer. AB - The serum CA125 level was determined by a one-step immunoradiometric assay method in patients with lung cancer. Increased serum CA125 levels were observed in 37.8% of patients with squamous cell cancer, in 30.0% of those with adenocarcinoma and in 60.0% of those with small call cancer. Most patients with increased serum CA125 levels were in stages 3 or 4. Patients with pleural effusions or ascites showed high serum CA125 levels. The survival time was significantly shorter in patients with increased serum CA125 levels than in those within normal limits. Among patients with advanced disease (stages 3 and 4), an increased serum CA125 level was again a poor prognostic factor (P less than 0.01). The existence of a pleural effusion did not correlate with the survival time. We conclude that CA125 is a good indicator of disease extent and serum levels correlate to the length of survival. PMID- 2223591 TI - Recruitment, follow-up and analysis times in clinical trials of cancer treatment: a case study. AB - A study has been made of the way in which the number of events available for analysis in a clinical trial was dependent on the recruitment period, the maximum follow-up time on individual patients and the length of time between the start of the trial and its analysis. The events considered were deaths, local recurrences and late radiation effects on normal tissue in patients treated for cancer of the laryngo-pharynx by two different fractionation regimes. The relationship is demonstrated between the number of events and the 95% confidence intervals that can be placed on differences between results in the two arms of the trial. It was found, in this particular trial, that no significant improvement in precision was gained by following up patients beyond 5 years or carrying out the analysis later than 2 years after the end of recruitment. The results are discussed in the context of the initial design of clinical trials, particularly those in which the aim is to test therapeutic equivalence. PMID- 2223592 TI - Predicting response to chemotherapy for patients with epithelial ovarian cancer using urinary polyamine excretion patterns. AB - Urinary polyamine (UPA) excretion patterns were measured in 39 patients with clinically evaluable epithelial ovarian cancer immediately before they were treated with a cycle of chemotherapy and 24-48 h after chemotherapy to ascertain if changes in UPA excretion patterns correlated with eventual response to treatment. Almost all of the 19 patients who responded to chemotherapy had a rise in the excretion of all UPA fractions after treatment while most patients with chemoresistant cancer showed only an increase in the excretion of the putrescine and spermine fractions. However, a two-fold increase in excretion of the spermidine fractions occurred exclusively in patients who would eventually respond to chemotherapy. This phenomenon was not seen in patients with chemoresistant cancer. If, 48 h after chemotherapy, a patient with epithelial ovarian cancer does not show at least a doubling of the urinary levels of spermidine, acetylspermidine or total polyamine excretion that chemotherapy should be stopped since it is unlikely to be effective. PMID- 2223594 TI - Bifidobacterium gallicum sp. nov. isolated from human feces. AB - A bifidobacterial isolate from human feces was found to have very low genetic relatedness to any previously described species of the genus. This strain, which also contained a unique type of peptidoglycan, L-lysine-L-alanine-L-serine (A3 alpha), is considered to represent a new species, which is designated Bifidobacterium gallicum. Its description is presented. The type strain is strain DSM 20093. gallicum. Its description is presented. The type strain is strain DSM 20093. PMID- 2223593 TI - Can the Spitzer Quality of Life Index help to reduce prognostic uncertainty in terminal care? AB - Data from an on-going trial of co-ordinating care for terminally ill cancer patients are used to investigate whether the Spitzer Quality of Life (QL) Index can be used to reduce prognostic uncertainty in terminal care. Four questions are addressed. First, can doctors and nurses distinguish between patients with a prognosis of more or less than 1 year? Second, do the medical and nursing staff differ in their ability to estimate prognosis? Third, are there differences in the length of life remaining between groups of patients with different QL Index scores? Fourth, how well does the QL Index predict the likelihood of individual patients dying within 6 months of assessment? Doctors and nurses assigned between 17 and 25% of patients to the wrong prognostic group and were as likely to over estimate as to under-estimate life expectancy. Medical and nursing staff did not differ in their ability to make prognostic judgements. Patients with a low QL Index score were more likely to die within 6 months than those with higher scores, but scores on the Index were not strong predictors of 6-month survival in individual patients. The Index is not accurate enough to be used to predict what sort of treatment terminally ill patients will require in the future and for how long. Nevertheless, it may prove valuable for those planning services for terminally ill cancer patients who require information on the levels of need in a population. PMID- 2223595 TI - Actinomadura fibrosa sp. nov. isolated from soil. AB - A new species of the genus Actinomadura which belongs to the Actinomadura madurae group of Goodfellow et al. was isolated from soil collected in Togo, West Africa. Traditional taxonomic methods plus contemporary fatty acid analysis techniques were used to establish the position of this species. Both physiological characteristics and fatty acid composition differentiate this strain from previously described species. This culture produces a new polyether antibiotic. It is characterized by the production of white to pink aerial hyphae on a limited number of media. The aerial hyphae appear asporogenous, forming thick fibers and projections instead of true spores. The reverse side is a distinctive reddish orange. This organism is resistant to 5% NaCl and grows at temperatures between 20 and 45 degrees C. Whole cells contain meso-diaminopimelic acid, galactose, glucose, mannose, madurose, phosphatidylinositol, and diphosphatidylglycerol. The menaquinones detected were MK-9(H6) and minor amounts of MK-9(H8). The name proposed for this new species is Actinomadura fibrosa; the type strain is strain NRRL 18348. PMID- 2223596 TI - Ureaplasma felinum sp. nov. and Ureaplasma cati sp. nov. isolated from the oral cavities of cats. AB - Seven ureaplasma strains isolated from the oral cavities of domestic cats (Felis domestica) were characterized and compared with the type strains of the three previously established species of this genus, Ureaplasma urealyticum (humans), Ureaplasma diversum (cattle), and Ureaplasma gallorale (chickens). The feline strains hydrolyzed urea but not arginine or glucose, were membrane bound, lacked cell walls, passed through 0.45-micron membrane filters, required cholesterol for growth, and formed minute (15- to 140-microns) colonies on agar medium. The seven feline strains fell into two distinct groups based on (i) their antigenic properties (determined by using the metabolism and growth inhibition and indirect immunoperoxidase procedures), (ii) their genomic properties (determined by using DNA-DNA hybridization and DNA cleavage pattern procedures), and (iii) their polypeptide profiles (determined by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses). Based on these properties, the two feline groups were unrelated to each other or to the three previously established species, and each group represents a distinct Ureaplasma species. Thus, we propose that ureaplasmas with these phylogenetic and genomic properties be given taxonomic status as Ureaplasma felinum and Ureaplasma cati, with strain FT2-B (= ATCC 49229 = NCTC 11709) and strain F2 (= ATCC 49228 = NCTC 11710) as the type strains, respectively. PMID- 2223598 TI - Phylogenetic relationships among species of Sterigmatomyces and Fellomyces as determined from partial rRNA sequences. AB - Sequence comparisons of selected regions from small (18S) and large (25S) subunit rRNAs were used to examine species relationships in the anamorphic yeast genera Sterigmatomyces, Fellomyces, Tsuchiyaea, and Kurtzmanomyces. On the basis of sequence similarity, the genus Sterigmatomyces is comprised of Sterigmatomyces halophilus and Sterigmatomyces elviae, while the genus Fellomyces contains three recognized species, Fellomyces fuzhouensis, Fellomyces penicillatus, and Fellomyces polyborus. Tsuchiyaea wingfieldii and Kurtzmanomyces nectairii are well separated from the other species which we examined. Comparison with selected teleomorphs indicated that the genus Fellomyces is closely related to the genus Sterigmatosporidium, whereas the genus Sterigmatomyces exhibited somewhat closer relatedness with the genus Leucosporidium. Impacting on our estimates of relatedness was the finding that nucleotide substitution in the rRNA regions which we examined seems relatively constant only among closely related species. PMID- 2223599 TI - Arylsulfatase activity of Mycobacterium avium, M. intracellulare, and M. scrofulaceum. AB - A rapid (3-h) arylsulfatase assay for cell suspensions of mycobacteria, in which p-nitrophenyl sulfate is used as the substrate, was developed. Arylsulfatase activity was found in cell suspensions of representative strains of Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum grown without the substrate in either Middlebrook 7H9 medium containing 0.2% (wt/vol) glucose and 0.05% (vol/vol) Tween 80 or Dubos broth medium, but was absent in cells grown in a low-pH, minimal medium containing 1% (vol/vol) Tween 80 as the sole carbon source. The levels of arylsulfatase activity of representatives of all three species were equal whether the activity was measured at pH 5.5, 6.5, or 7.5 and whether the cells were suspended in phosphate or Tris buffer. The addition of high levels of sulfate (present in the low-pH, Tween 80-containing medium) to Middlebrook 7H9 medium resulted in significantly lower levels of arylsulfatase activity in strains of M. scrofulaceum, but did not affect the levels in either M. avium or M. intracellulare. The levels of arylsulfatase activity were highest in M. avium, intermediate in M. intracellulare, and lowest in M. scrofulaceum strains. Polyacrylamide gel electrophoresis of crude extracts from late-log-phase cells of representatives of each species produced activity bands of unique mobility (one in M. avium, three in M. intracellulare [82, 5, and 13%], and two in M. scrofulaceum [60 and 40%]). PMID- 2223597 TI - DNA relatedness among established Ureaplasma species and unidentified feline and canine serogroups. AB - The levels of DNA relatedness among two unclassified feline ureaplasma serogroups, four unclassified canine ureaplasma serogroups, and the three previously established Ureaplasma species were examined and compared. The strains examined included five feline strains representing two feline serogroups, four canine strains representing four canine serogroups, and the type strains of the three established species. Each strain representing each species or serogroup exhibited 78% or more actual DNA homology with its homologous DNA, but less than 10% DNA homology with DNAs from the heterologous strains. These findings indicate that each of these human, bovine, avian, feline, and canine strains is genomically distinct. In addition, the three previously recognized species (Ureaplasma urealyticum [human], Ureaplasma diversum [bovine], and Ureaplasma gallorale [avian]), which were established on the basis of phenotypic properties, were also shown to be genomically distinct. The three feline serogroup SI strains were genomically related (from 89 to 100% DNA homology) to each other but were unrelated (less than 10% DNA homology) to the feline serogroup SII strains, indicating that these two feline serogroups are also genomically distinct. Conversely, the two feline serogroup SII strains were genomically very similar (from 83 to 100% DNA homology) to each other but were unrelated (less than 10% DNA homology) to the three feline serogroup SI strains. However, canine serogroup SI strain D1M-C exhibited 73% DNA homology with serologically distinct canine serogroup SII strain D29M, indicating that these strains representing two separate serogroups belong to the same genomic species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223600 TI - Recognition of biovar C of Fusobacterium necrophorum (Flugge) Moore and Holdeman as Fusobacterium pseudonecrophorum sp. nov., nom. rev. (ex Prevot 1940). AB - The cellular morphology, colonial morphology, biochemical properties, DNA base compositions, and DNA-DNA homolgies of three biovars of Fusobacterium necrophorum were examined. Some differences were found among the three biovars in cellular morphology, colonial morphology, and biochemical properties. The guanine-plus cytosine contents of DNAs from biovar C strains Fn521T (T = type strain), Fn522, and Fn520 were 30.4, 29.3, and 28.0 mol%, respectively, and the guanine-plus cytosine contents of DNAs from strains VPI 2891 (biovar A) and VPI 6161 (biovar B) were 31.3 and 32.0 mol%, respectively. Labeled DNA from biovar C strain Fn521T exhibited 96 and 82% relatedness to DNAs from biovar C strains Fn522 and Fn520, respectively; however, it exhibited only about 10% relatedness to DNAs from strains of biovars A and B. Labeled DNAs from strains VPI 2891 and VPI 6161 exhibited more than 70% relatedness to each other, but about 6 to 20% relatedness to DNAs from biovar C strains. Therefore, Fusobacterium pseudonecrophorum sp. nov., nom. rev. (ex Prevot 1940) is proposed for Fusobacterium necrophorum biovar C. The type strain is strain Fn521 (= JCM 3722). PMID- 2223601 TI - Proposal of three subspecies of Fusobacterium nucleatum Knorr 1922: Fusobacterium nucleatum subsp. nucleatum subsp. nov., comb. nov.; Fusobacterium nucleatum subsp. polymorphum subsp. nov., nom. rev., comb. nov.; and Fusobacterium nucleatum subsp. vincentii subsp. nov., nom. rev., comb. nov. AB - Heterogeneity among isolates of Fusobacterium nucleatum has been recognized for many years. The phenotypic properties of 340 strains considered to be F. nucleatum were examined. While these strains were phenotypically similar and fit the description of F. nucleatum, they could be differentiated into three groups on the basis of electrophoretic patterns of whole-cell proteins and DNA homology. Strains in groups I and II showed greater than 80% DNA homology within groups and less than 75% similarity between groups. Strains of group III demonstrated greater than 85% DNA homology to each other and less than 65% similarity to strains in groups I and II. We propose that Fusobacterium nucleatum be divided into the following three subspecies: Fusobacterium nucleatum subsp. nucleatum, with type strain ATCC 25586; Fusobacterium nucleatum subsp. polymorphum, with type strain ATCC 10953; and Fusobacterium nucleatum subsp. vincentii, with type strain ATCC 49256. PMID- 2223602 TI - Taxonomy of alkaliphilic Bacillus strains. AB - The DNA base compositions of 78 alkaliphilic Bacillus strains were determined. These strains were grouped as follows: DNA group A, guanine-plus-cytosine (G+C) content of 34.0 to 37.5 mol% (17 strains); DNA group B, G+C content of 38.2 to 40.8 mol% (33 strains); and DNA group C, G+C content of 42.1 to 43.9 mol% (28 strains). DNA group A includes the type strain of Bacillus alcalophilus Vedder 1934. DNA-DNA hybridization studies with DNA group A strains revealed that only one strain, strain DSM 2526, exhibited a high level of DNA homology with B. alcalophilus DSM 485T (T = type strain). Neither strain DSM 485T nor any other DNA group A strain is homologous to any of the Bacillus type strains with comparable base compositions. Six strains formed a distinct group containing three highly homologous strains and three strains exhibiting greater than 50% DNA homology. PMID- 2223603 TI - Leptospira interrogans serovar unipertama isolated in Malaysia. AB - A leptospiral isolate from a bovine kidney was found to be antigenically different from all previously recognized serovars of Leptospira interrogans based on the cross-agglutinin absorption test. The new serovar belongs to the Sejroe serogroup, and the name Leptospira interrogans serovar unipertama is proposed for it, with strain K2-1 as the reference strain. PMID- 2223604 TI - Description of Bacillus naganoensis sp. nov. AB - A new species, Bacillus naganoensis, is proposed for an obligately aerobic, moderately acidophilic, endospore-forming bacterium that produces a thermostable, aciduric pullulanase (EC 3.2.1.41). The organism was isolated from soil by selection on solid, pullulan-containing medium at pH 4.0 and 30 degrees C. The isolate required a medium pH of less than 6.5 for growth initiation. Fatty acid composition studies revealed that the major fatty acid of cells grown in nutrient broth supplemented with 1% starch was 14-methylpentadecanoic acid (iso-C16) at 45 mol%. The guanine-plus-cytosine content of the DNA of this organism was 45 +/- 2 mol%. A type culture has been deposited with the American Type Culture Collection, Rockville, Md., as strain ATCC 53909. PMID- 2223605 TI - Inter- and intrafamilial similarities of rRNA cistrons of the Pasteurellaceae. AB - We performed hybridizations between labeled rRNAs from seven representative members of the family Pasteurellaceae and from three other taxa on the one hand and DNAs from 53 strains known or presumed to belong to the Pasteurellaceae on the other hand. The members of the Pasteurellaceae are most closely related to members of the Enterobacteriaceae, the Vibrionaceae, the Aeromonadaceae, and the genus Alteromonas. The family Pasteurellaceae is very heterogeneous. There are at least seven rRNA branches. Several organisms with the same genus name are dispersed over the entire dendrogram. The "Histophilus ovis," [Haemophilus] ducreyi, [Actinobacillus] actinomycetemcomitans, and [Haemophilus] aphrophilus rRNA branches are separate and quite remote from the three authentic genera in this family; this might justify eventual later separate generic status. DNA-rRNA hybridization with suitable, labeled rRNA probes is an excellent method to establish whether an organism belongs in the Pasteurellaceae; e.g., some strains of Bisgaard's taxa 7, 13, and 16 and of the gas-producing "SP" group certainly belong in this family, whereas three bovine lymphangitis organisms (strains NCTC 10547, NCTC 10549, and NCTC 10553), [Haemophilus] piscium ATCC 10801T (T = type strain), and [Pasteurella] piscicida ATCC 17911 belong in the Enterobacteriaceae, the Aeromonadaceae, and the Vibrionaceae, respectively. PMID- 2223606 TI - Mycoplasma lactucae sp. nov., a sterol-requiring mollicute from a plant surface. AB - Strain 831-C4T (T = type strain), isolated from the surface of lettuce plants (Lactuca sativa) obtained from a retail food market, was shown to be a sterol requiring mollicute. Morphological examination of this organism by electron and dark-field microscopic techniques showed that it consists of small, nonhelical, nonmotile, pleomorphic coccoid cells, with individual cells surrounded by a single cytoplasmic membrane. No evidence of a cell wall was observed. The organism grew rapidly in all conventional culture medium formulations for mollicutes in either aerobic or anaerobic environments. The optimum temperature for growth was 30 degrees C, but multiplication occurred at 18 to 37 degrees C. Strain 831-C4T catabolized glucose, but hydrolysis of arginine or urea could not be demonstrated. The genome size of strain 831-C4T was determined to be about 569 megadaltons, while the base composition (guanine-plus-cytosine content) of the DNA was 30.0 mol%. Recent studies in which we compared the 16S rRNA sequences of strain 831-C4T with those of more than 40 other mollicutes indicated that this organism is phylogenetically related to the Spiroplasma-Mycoplasma mycoides clade. Strain 831-C4T was serologically unrelated to the type strains of previously described Mycoplasma species and to 18 other unclassified sterol requiring isolates cultivated from various animal, plant, or insect sources. Strain 831-C4T (= ATCC 49193) is the type strain of Mycoplasma lactucae sp. nov. PMID- 2223607 TI - Mycoplasma melaleucae sp. nov., a sterol-requiring mollicute from flowers of several tropical plants. AB - Three sterol-requiring mollicutes from floral surfaces of two tropical plant species (Melaleuca quinquenervia and Melaleuca decora) and a single isolate from a flower of the silk oak (Grevillea robusta) were serologically indistinguishable. Strain M1T (T = type strain), isolated from Melaleuca quinquenervia, was chosen for characterization. Light and electron microscopic observations of strain M1T revealed nonhelical, nonmotile, pleomorphic coccoid cells surrounded by a single cytoplasmic membrane. No evidence of a cell wall was observed. The organism grew well in SP-4 medium, but no sustained growth occurred in conventional mycoplasma media containing horse serum. The optimum temperature for growth was 23 degrees C, but multiplication occurred over a temperature range of 10 to 30 degrees C. Growth was not observed at temperatures above 30 degrees C. Strain M1T and related strains (strains M5, M10, and SO1) catabolized glucose but hydrolyzed neither arginine nor urea. The size of the strain M1T genome was about 561 megadaltons, while the guanine-plus-cytosine content of the DNA was about 27.0 mol%. The organism was serologically unrelated to the type strains of the 80 previously recognized Mycoplasma species or to 18 other unclassified sterol-requiring strains cultivated from animal, plant, or insect sources. Recent sequencing studies of 16S rRNA demonstrated that strain M1T is a member of a clade that contains the type species of the genus Mycoplasma. Strain M1 (= ATCC 49191) is the type strain of Mycoplasma melaleucae sp. nov. PMID- 2223608 TI - Actinobacillus rossii sp. nov., Actinobacillus seminis sp. nov., nom. rev., Pasteurella bettii sp. nov., Pasteurella lymphangitidis sp. nov., Pasteurella mairi sp. nov., and Pasteurella trehalosi sp. nov. AB - Evidence from numerical taxonomic analysis and DNA-DNA hybridization supports the proposal of new species in the genera Actinobacillus and Pasteurella. The following new species are proposed: Actinobacillus rossii sp. nov., from the vaginas of postparturient sows; Actinobacillus seminis sp. nov., nom. rev., associated with epididymitis of sheep; Pasteurella bettii sp. nov., associated with human Bartholin gland abscess and finger infections; Pasteurella lymphangitidis sp. nov. (the BLG group), which causes bovine lymphangitis; Pasteurella mairi sp. nov., which causes abortion in sows; and Pasteurella trehalosi sp. nov., formerly biovar T of Pasteurella haemolytica, which causes septicemia in older lambs. PMID- 2223609 TI - Evidence that Bacteroides nodosus belongs in subgroup gamma of the class Proteobacteria, not in the genus Bacteroides: partial sequence analysis of a B. nodosus 16S rRNA gene. AB - The taxonomic status of the anaerobe Bacteroides nodosus has for some time been uncertain. To resolve this uncertainty, the distal portion of a 16S rRNA gene from this important ovine pathogen was cloned, mapped, and sequenced. A comparison of the sequence with the sequences of 16S rRNA molecules from other bacteria indicated that B. nodosus is more closely related to Escherichia coli and other members of the class Proteobacteria than to Bacteroides fragilis or the bacteroides-flavobacterium-cytophaga phylum. The evidence from the comparison of sequence signatures suggests that B. nodosus is not a member of the genus Bacteroides but that it belongs in subgroup gamma of the class Proteobacteria. PMID- 2223610 TI - Mycoplasma somnilux sp. nov., Mycoplasma luminosum sp. nov., and Mycoplasma lucivorax sp. nov., new sterol-requiring mollicutes from firefly beetles (Coleoptera: Lampyridae). AB - Strain PYAN-1T (T = type strain), which was isolated from a pupal gut of the firefly beetle Pyractonema angulata, and strains PIMN-1T and PIPN-2T, which were isolated from guts of adult Photinus marginalis and Photinus pyralis fireflies, respectively, were demonstrated to be sterol-requiring mollicutes. Cells of the three strains were shown by electron and dark-field microscopy to be small, pleomorphic, nonhelical, nonmotile bodies surrounded by single membranes. No evidence of a cell wall was observed, and the organisms were not susceptible to 500 U of penicillin per ml. The three strains grew rapidly in SP-4 broth medium. Strains PIMN-1T and PIPN-2T grew in medium supplemented with bovine serum fraction, but strain PYAN-1T did not. All three strains grew on solid media when the cultures were incubated aerobically, but only strains PYAN-1T and PIPN-2T formed colonies when anaerobic conditions were employed. The three strains catabolized glucose but hydrolyzed neither arginine nor urea. All of the strains grew at temperatures of 18 to 32 degrees C; strains PYAN-1T and PIMN-1T also grew at 10 degrees C. The optimal temperature for growth for strains PYAN-1T and PIPN 2T was 30 degrees C; strain PIMN-1T grew equally well at 30 or 32 degrees C. None of the three strains grew at 37 degrees C. The genome sizes of strains PYAN-1T, PIMN-1T, and PIPN-2T were about 527 (478 to 589), 570 (480 to 630), and 762 (635 to 871) megadaltons, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223611 TI - Amycolatopsis methanolica sp. nov., a facultatively methylotrophic actinomycete. AB - The generic position of a gram-positive, facultatively methylotrophic actinomycete known as Nocardia sp. strain 239 was determined by comparing reverse transcriptase sequences of 16S rRNA. The assignment of the organism to the genus Amycolatopsis was strongly supported by chemotaxonomic and morphological data. A comparison with the type strains of validly described Amycolatopsis species showed that the organism formed the nucleus of a new species. The name proposed for this new species is Amycolatopsis methanolica. The organism has been deposited in the National Collection of Industrial Bacteria as NCIB 11946. PMID- 2223613 TI - Revised nomenclature of Campylobacter laridis, Enterobacter intermedium, and "Flavobacterium branchiophila". PMID- 2223612 TI - Prevotella, a new genus to include Bacteroides melaninogenicus and related species formerly classified in the genus Bacteroides. AB - It was recently proposed that the genus Bacteroides should be restricted to Bacteroides fragilis (the type species) and closely related organisms (viz., B. caccae, B. distasonis, B. eggerthii, B. merdae, B. ovatus, B. stercoris, B. thetaiotaomicron, B. uniformis, and B. vulgatus). By contrast, the moderately saccharolytic, predominantly oral Bacteroides species, which include B. melaninogenicus, B. oralis, and related species, form a phenotypically and phylogenetically coherent group of species which differ so significantly from the emended description of the genus Bacteroides that they should not be classified in the same genus. Therefore, we formally propose that these species be reclassified in a new genus, Prevotella. The type species is Prevotella melaninogenica. PMID- 2223614 TI - [Bone marrow transplantation in children. Nursing aspects]. PMID- 2223615 TI - [Bone marrow transplantation in childhood]. PMID- 2223617 TI - [Pioneers in pediatrics. Charles West (1816-1898)]. PMID- 2223616 TI - [Modern aspects of insulin treatment of diabetic children and adolescents]. PMID- 2223618 TI - [A look into the past. Infant care at the turn of the century]. PMID- 2223619 TI - [Treatments for children]. PMID- 2223620 TI - [Pathology of the external female genitalia]. PMID- 2223622 TI - [Diseases of the hematologic cell systems. 2. Diseases of the white blood cells]. PMID- 2223621 TI - [Report on experiences in Japan]. PMID- 2223623 TI - [Alternative nutritional possibilities for neonates and infants]. PMID- 2223625 TI - [Cooperation between pediatricians and pediatric nurses in the home]. PMID- 2223624 TI - [Pioneers in pediatrics. Himself a pioneer. Letter to Dr. Johannes Oehme on the occasion of his 75th birthday on 3 September 1990]. PMID- 2223626 TI - [Sickle and pigeon-toed foot]. PMID- 2223627 TI - The use of unrelated marrow donors for transplantation. PMID- 2223629 TI - Reactivity of a human monoclonal antibody against Rh D with the intermediate filament protein vimentin. AB - The human IgM anti-Rh D antibody MAD-2 has previously been shown to react with human and animal tissues and leucocytes. Double labelling immunofluorescence with MAD-2 and a mouse monoclonal antibody against vimentin, the intermediate filament protein of cells of mesenchymal origin, showed coincidental staining which was distinct from that seen with antibodies against other cytoskeletal proteins. Using immunoblotting, both MAD-2 and anti-vimentin reacted with a 55 kDa tissue component, and with purified vimentin. These results show that the major tissue and leucocyte protein recognized by MAD-2 is vimentin. PMID- 2223628 TI - Induction of patching and its reversal on surface-activated human platelets. AB - Fibrinogen coupled to colloidal gold (Fgn/Au) has been used to follow GPIIb-IIIa receptors on surface-activated platelets and to evaluate the effects of the anti actin agent, cytochalasin B (CB), on the movement of receptor-ligand complexes. Fgn/Au binds diffusely to spread platelets, but is translocated rapidly from the peripheral margin to cell centres and to channels of the open canalicular system (OCS). CB added after spreading and incubation with Fgn/Au reverses the centripetal movement of receptor-ligand complexes. Fgn/Au particles move back toward the margins of spread cells and form patches. The patches of receptor ligand complexes overlie segments of the OCS filled with Fgn/Au. Washing out the CB reverses the process and receptor-ligand complexes are again translocated toward platelet centres. PMID- 2223631 TI - Molecular charge heterogeneity of human serum erythropoietin. AB - The charge heterogeneity of human serum erythropoietin (S-Epo) was studied in 89 serum specimens from 78 subjects by zone electrophoresis in 0.17% agarose suspension at pH 8.6. The electrophoretic elution profiles of S-Epo were determined with a radioimmunoassay for Epo. The number of Epo peaks indicated that at least 20-30 different forms of Epo were present in a single serum specimen. The median charge of Epo, estimated as its median electrophoretic mobility, was determined for each serum specimen. This median charge was measured in 10 healthy adults, 46 patients with anaemia, six patients with secondary polycythaemia, one patient with polycythaemia vera treated by phlebotomy, and six healthy newborn infants (cord sera). Forty-four of the patients with anaemia had a median charge of S-Epo within the reference range for healthy adults, while all the patients with polycythaemia and the newborn infants had less negatively charged forms of S-Epo. In nine patients in whom the S-Epo level had a circadian rhythm, the forms of S-Epo in the evening were less negative than those in the morning. The median charge of recombinant preparations was much less negative than that of S-Epo in healthy individuals, while that of the 2nd International Reference Preparation was more negative than in any of the 78 subjects analysed. A significant change to less negatively charged S-Epo forms was observed 24 h after a subcutaneous injection of recombinant Epo in one patient, who before the injection had a normal median charge and concentration of S-Epo. In conclusion, Epo exhibits a considerable charge heterogeneity in individual serum specimens, the forms of S-Epo in the morning may differ from those in the evening, those in adults differ from those in newborn infants, and those in patients with anaemia differ from those in polycythaemia. The results also suggest that the methods used in this study may be useful for detecting the presence of injected recombinant Epo in the blood in persons with a normal endogenous Epo production. PMID- 2223630 TI - Interaction of monocytes and T cells in the regulation of normal human megakaryocytopoiesis in vitro: role of IL-1 and IL-2. AB - Autologous or allogeneic peripheral blood T cells can stimulate the human megakaryocyte progenitor cell (CFU-Meg)-derived colony formation in a dose dependent fashion in agar cultures of nonadherent (NA), T cell-depleted (NT) bone marrow (BM) cells. Low concentrations of monocytes and T cells can collaborate in the stimulation of CFU-Meg colony formation or in the production of megakaryocyte colony stimulating factor (Meg-CSF) by T cells in the presence of mitogens or IL 2. Monocytes alone can produce only negligible Meg-CSF under any conditions. When monocyte conditioned medium (CM) was added to T cell-stimulated NA, NT BM cell cultures, CFU-Meg colony growth was appreciably increased compared with that stimulated by T cells alone. Dose-dependent increase in CFU-Meg colony growth was noted when varying concentrations of IL-1 were added to T cell-stimulated NA, NT cell cultures, although IL-1 itself could support no CFU-Meg colony growth in the absence of T cells. These data suggest that a synergistic interaction between T cells and monocytes during the production of Meg-CSF by T cells could be partly mediated by IL-1. IL-2 was found to stimulate Meg-CSF production by T cells in the presence or absence of mitogens. IL-2-stimulated Meg-CSF production by T cells was augmented by the addition of monocytes. Although IL-2 itself had no stimulatory effect on CFU-Meg colony growth, dramatic augmentation in the CFU-Meg colony number was noted when IL-2 was added to T cell-stimulated NA, NT cell cultures. High concentrations of monocytes and prostaglandin E (PGE) inhibited the CFU-Meg colony formation. These results suggest that IL-1 and IL-2 may play a stimulatory role on the normal human in vitro megakaryocytopoiesis, and may be involved in the development of reactive thrombocytosis and bone marrow megakaryocytic hyperplasia in various inflammatory diseases. PMID- 2223632 TI - Serum erythropoietin changes in autologous and allogeneic bone marrow transplant patients. AB - Sequential changes in serum erythropoietin (sEPO) levels were measured by radioimmunoassay in six patients receiving autologous rescue (AR) and 11 patients receiving an allogeneic bone marrow transplant (BMT) for malignant disease. Longitudinal studies showed an inverse relationship between sEPO and haemoglobin levels in the autologous rescue and allogeneic transplant patients throughout the 130 d post-transplant study period. Early post-conditioning EPO responses were normal for the haemoglobin level in both groups, but after day 14 post transplant, erythropoietin production in response to anaemia became impaired in one autologous rescue patient and eight of the 11 allogeneic transplant patients. There was no clear association between late impairment of sEPO production and conditioning therapy, infection, graft-versus-host disease, immunosuppressive therapy or serum creatinine. Blood transfusion requirements were similar for both groups in the first month after transplantation, but from days 31 to 90 post transplant, BMT patients required an average of 5.5 units per patient compared with 1 unit per patient for the autologous group. Marrow transplant procedures do not affect early EPO responses but may diminish late responses. The potential value of exogenous rHuEPO in hastening engraftment and decreasing transfusion requirements, particularly for those patients who appear to have impaired EPO responses, remains to be shown by clinical trials. PMID- 2223633 TI - A splicing mutation accounts for the lack of p53 gene expression in a CML blast crisis cell line: a novel mechanism of p53 gene inactivation. AB - Alterations of the p53 anti-oncogene have recently been found to occur frequently in the blast crisis of chronic myelocytic leukaemia. The p53 gene may be altered by gross structural alterations or by point mutations in the coding sequence. We now report a novel mechanism of gene inactivation in a blast crisis cell line where a mutation in a splice donor site at the 5' end of the fifth intron of the gene interrupts RNA processing and gene expression. PMID- 2223634 TI - Long-term stable mixed chimaerism following allogeneic marrow transplantation for severe aplastic anaemia. PMID- 2223635 TI - Deferoxamine-induced restoration of haematopoiesis in myelofibrosis secondary to myelodysplasia. PMID- 2223636 TI - Sporadic HTLV-I associated adult T-cell leukaemia (ATL) in the U.K. PMID- 2223637 TI - Regression of diffuse osteosclerosis in hairy cell leukaemia after treatment with interferon. PMID- 2223639 TI - Transient spontaneous remission in a case of adult acute myelogenous leukaemia. PMID- 2223638 TI - The first reported case of hypoglycaemia as the presenting feature of invasive plasmacytoma with a paraprotein band and grossly elevated insulin levels. PMID- 2223640 TI - Lack of reversal with verapamil of drug resistance in multiple myeloma. PMID- 2223641 TI - Translocations involving 5q35 may also be associated with plasma cell leukemia. PMID- 2223642 TI - The distribution of CD45R, CD29 and CD45RO (UCHL1) antigens in mature CD4 positive T-cell leukaemias. PMID- 2223643 TI - Use of leukocyte-poor blood components in acute myeloblastic leukemia does not affect disease-free survival in first complete remission. PMID- 2223645 TI - A study of prognostic factors in blast crisis of Philadelphia chromosome-positive chronic myelogenous leukaemia. AB - In 80 patients with Ph-positive chronic myelogenous leukaemia the main clinical, haematological and cytogenetical data were recorded at diagnosis of blast crisis and evaluated for prognostic significance. At the time of the analysis 73 patients had died, with a median survival of 4-8 months from diagnosis of blast crisis for the whole series. When analysed as a time-dependent variable, the achievement of a favourable response to chemotherapy resulted in a longer patient's survival. On the other hand, the univariate analysis identified six pretreatment characteristics associated with a poorer prognosis: a longer chronic phase, presence of extramedullary blastic involvement, a platelet count below 200 x 10(9)/l, a less marked leucocytosis, a blood blast cell percentage higher than 10%, and presence of trisomy 8. The latter parameters were included in a multiple regression model together with the blast cell phenotype (lymphoid versus non lymphoid), and only four of them (trisomy 8, duration of chronic phase, platelet count, and leucocyte count) retained their prognostic influence. When the therapeutical response was also included in the regression model, it proved to be the most important prognostic variable, followed by trisomy 8, length of chronic phase, extramedullary disease, and platelet count, whereas the leukocyte count lost its predictive value. Thus, in spite of the short overall survival of blast crisis patients, the identification of prognostic factors in such a haematological condition may be of interest, especially in the interpretation of new therapeutical approaches. PMID- 2223644 TI - Different sensitivity of normal and leukaemic progenitor cells to Ara-C and IL-3 combined treatment. AB - In the present study the effects of a combined treatment with cytosine arabinoside (Ara-C) and interleukin-3 (IL-3) on acute myeloblastic leukaemia clonogenic cells and on normal haemopoietic progenitors was investigated, with the aim of improving the tumoricidal effect of cycle specific drugs. Blast cells from 24 acute myeloblastic leukaemia (AML) patients were screened with a short term proliferative assay based on 3H-thymidine (3H-TdR) uptake for their response to IL-3. To evaluate the synergism between the growth factor and Ara-C, the cells were pretreated for 3 d in liquid culture in the presence or absence of IL-3 (10 U/ml) and for the last 24 h with Ara-C (3 micrograms/ml). The cells were then washed and seeded in semisolid media to assess their clonogenic ability. The results showed that, in those cases which were good responders to IL-3 in the 3H TdR uptake assay (19 out of 24), Ara-C exposure eliminated a greater proportion of clonogenic cells if pretreated with IL-3 than if untreated (P less than 0.001), while in cases unresponsive to IL-3 this effect was not significant. Moreover, when the same protocol was applied to bone marrow cells from normal donors, it was found that IL-3 pretreatment did not significantly enhance the toxic effect of Ara-C on day 14 granulocyte-macrophage colony forming units (CFU GM) and erythroid burst forming units (BFU-E). Finally IL-3 pretreatment was also able to increase the cytotoxic effect of Ara-C on leukaemic cells co-cultured, to simulate clinical AML remission, with normal bone marrow cells. The results indicate that IL-3 may improve the therapeutic index of cycle-specific drugs in AML therapy. PMID- 2223646 TI - The role of alternative splicing patterns of BCR/ABL transcripts in the generation of the blast crisis of chronic myeloid leukaemia. AB - Three major types of mRNA can be expressed as a result of the Philadelphia translocation, dependent on the position of the break within the BCR gene on chromosome 22. In addition, alternative splicing of the mRNA transcribed from the BCR/ABL fusion gene has been reported and it has been suggested that this may play a role in the generation of the acute phase of Philadelphia positive chronic myeloid leukaemia (CML). We have examined the fusion RNA present in 24 cases of chronic phase CML and 21 cases of patients with CML in blast crisis using the polymerase chain reaction. In no case was it possible to detect the presence of the e1a2 junction which encodes the p190 hybrid protein product. We conclude that the acquisition of the p190 does not play a significant role in the generation of the blast crisis of CML. Neither could we detect a significant difference in the number of cases which simultaneously express both b2a2 and b3a2 junction products in samples isolated from chronic phase and blast crisis. In the series analysed by ethidium bromide stained gels, there was, however, an increase in the percentage of cases expressing the b3a2 junction in the mononuclear cells of blast crisis patients as compared to the white blood cells of patients in chronic phase. PMID- 2223647 TI - ABL proteins in Philadelphia-positive acute leukaemias and chronic myelogenous leukaemia blast crises. AB - The Philadelphia chromosome (Ph1) is present in 95% of chronic myelogenous leukaemias (CML) and 15% of acute lymphoblastic leukaemias (ALL). This cytogenetic marker is due to a t(9;22) translocation, which causes a rearrangement of the ABL oncogene. In order to better define the relationship between type of genomic rearrangement, variant ABL protein expressed and haematological phenotype, a series of Ph1-positive acute leukaemias, both myeloblastic (AML) and lymphoblastic, and several CML lymphoid blast crises have been analysed at the DNA and protein level. The results confirm the presence of the ABL protein P210 in all cases of CML, ALL and AML positive for rearrangement in the bcr region of chromosome 22, and, surprisingly, in one AML case apparently negative for bcr rearrangement. The ABL protein P190 was found to be present only in cases of ALL negative for bcr rearrangement. Polymerase chain reaction (PCR) analysis of the types of 9/22 junctions present in the mRNA of CML lymphoid blast crises showed no evidence of 'ALL-type' transcripts. PMID- 2223648 TI - Natural history of stage A chronic lymphocytic leukaemia untreated patients. French Cooperative Group on Chronic Lymphocytic Leukaemia. AB - In chronic lymphocytic leukaemia (CLL), stage A was defined in 1979 as the best prognostic group of the three-stage (A, B, C) classification which was thereafter adopted by an International Workshop on CLL. Recently, the question of whether or not all stage A patients should be treated was raised by authors who described potential harmful effects of treatment among stage A patients and heterogeneity of stage A with respect to survival and disease progression. In this work, we studied the natural history of stage A-CLL in order to determine on which grounds a decision to treat should be made. We performed a prognostic study on 309 untreated stage A-CLL patients enrolled in a randomized clinical trial from 1980 to 1985. Our aim was to segregate a subgroup with a low probability of disease progression and death. We used three endpoints: overall survival (50 deaths), disease progression to stage B or C (78 events) and disease progression to stage C (39 events). Multivariate analyses, using Cox's model, selected nine variables as having a prognostic value for at least one endpoint, namely age, sex, general symptoms, involved axillary lymph node, splenomegaly, haemoglobin, platelets, lymphocyte count and bone-marrow infiltration. By considering the three endpoints jointly, we obtained a proposed definition of smouldering CLL based on four variables, namely haemoglobin level, lymphocyte count, the number of enlarged areas and bone-marrow infiltration. However, we did not succeed in better defining smouldering CLL than in a previous proposal, based on haemoglobin level and lymphocyte count. Moreover, whatever the definition used, including other previous works, disease progression within 5 years was still observed for about 10% of patients with smouldering CLL. Future attempts to define smouldering CLL could perhaps benefit from using biological markers. PMID- 2223649 TI - The 14;18 translocation in European cases of follicular lymphoma: comparison of Southern blotting and the polymerase chain reaction. AB - The 14;18 chromosomal translocation is widely recognized as a cytogenetic abnormality associated with follicular lymphomas, but estimates of its frequency in this type of lymphoma vary widely from less than 50% to almost 90%. Furthermore, no extensive data have been published on the frequency of t(14;18) in European cases of follicular lymphoma. Lymph nodes from 51 patients with follicular lymphomas obtained from two European centres (Oxford and Copenhagen) were examined for the presence of this translocation. Southern blotting and the polymerase chain reaction (PCR) were used in 26 cases and the PCR alone in 25 cases (from which only degraded DNA or formalin fixed samples were available). DNA probes capable of detecting rearrangement at both the major and the minor breakpoint regions were employed. We could detect t(14;18) in only 21 out of 51 cases (41%). However, a review of the literature showed that comparable results have been obtained previously using both cytogenetic and molecular biological techniques and our results support the view that the global incidence of t(14;18) in follicular lymphoma is no greater than 70%. Furthermore, this study has indicated that the PCR is a reliable method for identifying t(14;18) when only formalin-fixed paraffin-embedded tissue or degraded DNA is available. PMID- 2223650 TI - Translocation of bcl-2 gene in non-Hodgkin's lymphomas in Hong Kong Chinese. AB - The close association between translocation of the proto-oncogene bcl-2 and follicular lymphomas has been well established in Caucasian patients and the de regulation of bcl-2 has been implicated in follicular lymphomagenesis. Similar molecular structural alterations have also been detected in diffuse lymphomas with a previous history of a follicular pattern as well as in a smaller proportion of de novo diffuse lymphomas. There is a lower incidence of follicular lymphomas in Chinese. In order to investigate further this phenomenon, we used bcl-2 translocation as a genetic marker of follicular lymphomas, to study 31 cases of B cell non-Hodgkin's lymphomas in Chinese patients by Southern blot analysis. Eight out of 16 cases of follicular lymphomas showed bcl-2 translocation with involvement of the major breakpoint region (MBR). Six of these cases utilized breakpoints within the 4.3 kb HindIII fragment, while in two cases the breakpoints were more dispersed, but still within the BamHI fragment. An additional case of follicular lymphoma showed translocation of bcl-2 gene with involvement of the minor cluster region (mcr), making a total of nine out of 16. None of the 15 cases of diffuse lymphomas showed similar molecular structural alterations. These data show that bcl-2 translocation is present in 57% of follicular lymphomas in Chinese patients, and support the notion that bcl-2 translocation is a consistent marker for follicular lymphomas irrespective of ethnic differences. As the translocation is not detected in the diffuse lymphomas, there is no evidence to suggest that the low incidence of follicular lymphomas in Chinese patients is due to a greater tendency for follicular tumours to progress rapidly and present as diffuse lymphomas. PMID- 2223651 TI - Interleukin-4 regulates mRNA accumulation of macrophage-colony stimulating factor by fibroblasts: synergism with interleukin-1 beta. AB - We demonstrate that macrophage-colony stimulating factor (M-CSF) is expressed in human fibroblasts at the mRNA and protein level. Following activation with both interleukin (IL)-1 beta and IL-4, fibroblasts synthesized M-CSF transcripts detectable by Northern blot analysis with peak expression occurring at 8 h and 12 h, respectively. Exposure of fibroblasts to both cytokines resulted in M-CSF protein release at 60 h of c. 500 U/ml (for IL-1 beta) and 1000 U/ml (for IL-4), relative to a control preparation of recombinant human M-CSF in a murine bone marrow colony assay. Both interleukins synergized to enhance M-CSF mRNA accumulation and their ability to induce M-CSF transcripts could be abolished by treatment with specific neutralizing antibodies. These observations provide support for the idea that fibroblasts may control monocyte/macrophage development and function, and that IL-1 beta and IL-4 are involved in the regulation of this process. PMID- 2223652 TI - Antithrombotic potencies of heparins in relation to their antifactor Xa and antithrombin activities: an experimental study in two models of thrombosis in the rabbit. AB - Our purpose was to determine the relative contribution of the antifactor Xa and antithrombin activities of heparin to its antithrombotic potency. The antithrombotic activities of unfractionated heparin (UH), two low molecular weight heparins (LMWH, CY 216 and CY 222) with increasing anti-factor Xa/antithrombin ratio and a synthetic pentasaccharide (PS) with high affinity to antithrombin III and no antithrombin activity were evaluated. In the Wessler thromboplastin model, the most potent antithrombotic agent, on a weight basis, was UH followed by CY 216, CY 222 and the PS which was 40 times less potent than UH. On an antithrombin unit basis, the antithrombotic potencies of UH, CY 216 and of CY 222 were equivalent. Thus, in this model, the antithrombotic effect results from the catalytic action of UH or LMWH on thrombin inhibition. In the Wessler serum model, on a weight basis, the antithrombotic effectiveness of UH was unchanged, those of CY 216 and CY 222 were doubled, and that of the PS was increased 10 times. On an anti-factor Xa unit basis, CY 216 was as effective as UH, and PS as effective as CY 222. On an antithrombin unit basis, CY 216 and CY 222 were equivalent and more potent than UH. Thus, in this model, the antifactor Xa activity of heparin becomes important for its antithrombotic property. After a single subcutaneous injection of 1000 antifactor Xa U/kg, the antithrombotic effects of UH were maintained for more than 14 h in the two models. After injection of the same dose of CY 216 significant antithrombotic effects were observed only for 9 h, in the Wessler-thromboplastin model but for 18 h in the Wessler-serum model. At that time, no detectable antithrombin activity was measurable in the plasma while 0.11 units of antifactor Xa activity/ml was detected. Thus, the relative contribution of the anti-factor Xa and antithrombin activities to the antithrombotic effect of a LMWH differs according to the nature of the thrombogenic stimulus. PMID- 2223654 TI - [The effects of treatment with unpurified milk-based preparations in experimental influenza virus infection in mice]. PMID- 2223653 TI - The continuous decrease in the number of SSPE annual cases ten years after compulsory anti-measles immunization. AB - The record of SSPE cases diagnosed immunochemically and serologically in our laboratory, standing for about 60% of the total new cases reported in our country, shows a significant decrease in the incidence in 1988-89 (from 5.21 new cases per year per million total population in 1987 to 1.82 cases in 1988). In 85% of the patients, SSPE onset occurred at the age of 10 years or more, suggesting the possibility of a primary measles infection before anti-measles immunization became compulsory. High serum and CSF anti-measles antibody titres in recently diagnosed patients show subclinical long-term courses. Further serologic tests for viruses inducing persistent infections (herpes viruses, AgHBs and HIV) do not show any difference when compared to a control group excepting an increased incidence of anti-cytomegalic titres. PMID- 2223655 TI - [The mechanisms of persistent measles virus infection in HEp-2 cells]. AB - Persistent infection with Edmonston strain of measles virus was established in a highly susceptible clone of HEp-2 cells. The morphological and cytogenic aspects of persistent infection are presented. Carriage of measles virus in cells persistently infected is marked by important differences between standard Edmonston strain and virus stocks isolated from time to time from the carrier state. It is especially significant that cell fusion capacity decreased in amount concordant with the drop in the yield of infectious virus. Addition of UV inactivated Sendai virus, trypsin treatment or incubation at suboptimal temperatures precipitate the cytocidal effect of measles virus. Some clinical implications of reactivation of the lytic cycle in the carrier state are suggested. PMID- 2223656 TI - [Inframicrobiological research on cases of insulin-dependent diabetes mellitus]. AB - A group of 55 patients with insulin-dependent diabetes mellitus, aged from 8 to 40 years, was followed and compared to a group of controls, in view of detecting a possible relation between the presence of inframicrobial agents and diabetes pathogenesis. The investigations revealed, in patients, significantly higher positivity rate of antibodies against mumps (27% versus 16.3% in controls), parainfluenza type 1 (45.4% versus 29.1%) and Epstein-Barr (54.5% versus 10.9%) viruses, and Mycoplasma pneumoniae (43.6 versus 18.2%). PMID- 2223657 TI - Evaluation of efficacy of pooled sera in a human immunodeficiency virus antibody prevalence in population surveys. AB - The pooling of five individual serum samples for the detection of human immunodeficiency virus type 1 (HIV-1) antibodies was examined to assess whether testing pooled versus individual sera was technically feasible. Detection of HIV 1 antibodies was performed using a competitive enzyme immunoassay (EIA) Wellcozyme HIV Recombinant commercially available kit. Positive, weak positive and negative sera or HIV-1 antibody from Wellcozyme HIV Recombinant, Du Pont ELISA, SERODIA HIV Mast Diagnostica and from "Stefan S. Nicolau" Institute of Virology (NIV) collection were pooled in various dilutions with control negative sera for HIV-1 antibodies. When positive sera were pooled 1:4 with negative sera, results remained reactive in the same range of positivity and when cut off control sera were pooled 1:4 with negative sera samples remained in the cut off range. For reliability we considered cut of values of pooled sera probes an A 450 absorbance 0.2 units higher than the absorbance of cut-off-control from Wellcozyme HIV Recombinant kit B. Samples of pooled sera that have absorbance A 450 lower, equal or 0.2 units higher than the absorbance of cut off-control of Wellcozyme were considered positive and the five sera were tested as individual probes. The positive probes thus found were retested in duplicate using the original sample source. Negative samples of pooled sera do not have to be retested, this being the main advantage of this technique. Also positive sera (controls of from NIV collection) were pooled with HIV-1 antibody negative sera which were positive for rheumatoid factor (RF).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223658 TI - Pregnant women at work: a study of ethnic minority risk in Leicestershire. AB - Possible reasons for the excess risk of perinatal mortality experienced by Asian women living in Leicestershire who work during pregnancy were investigated. This entailed a detailed examination of the work undertaken locally by a group of pregnant Asian women and comparison with the work undertaken by an occupationally matched group of pregnant non-Asian women. A total of 306 pregnant women were interviewed. The results suggest that the two ethnic groups experienced similar working conditions, and most of the women continued working until the 29th week of pregnancy. The Asian women worked significantly longer hours on average than the non-Asian group, and were more likely to report financial dependence by the family upon their earnings. PMID- 2223659 TI - Mortality of a cohort of tin miners 1941-86. AB - The mortality patterns of United Kingdom tin miners were examined in relation to calendar period and duration of underground work with particular attention to lung cancer and exposure to radon. Subjects were all men who had worked for at least one year between 1941 and 1984 at one of two United Kingdom tin mines and for whom a complete work history could be constructed from mine records. Standardised mortality ratios (SMRs) were calculated using national (England and Wales) rates. The pattern of SMRs in relation to potential explanatory variables was analysed using Poisson regression methods. Mortalities from lung cancer and silicosis (including silicotuberculosis) were significantly raised and showed a significant relation with duration of underground work (mortality from stomach cancer was raised in both underground and surface workers, but not significantly). Excess mortality from silica related disease declined steeply from 35% among workers first exposed before 1920 to 1% among those first exposed after 1950. Thirteen surface workers with known exposure to arsenic had high rates of lung and stomach cancer. The SMR for lung cancer showed a consistent pattern in relation to duration of underground exposure, rising from 83 (observed/expected = 8/9.6) for surface workers (without exposure to arsenic) to 447 (15/3.4) for workers with more than 30 years underground exposure. Examination of the SMR for lung cancer by total underground exposure, age, and time since last exposure gave rise to a model for the expression of risk which depends only on total exposure and time since exposure. The fitted model implies that the effect of exposure to radon in a given year has no effect on risk for 10 years, then rapidly rises to a maximum from which the excess risk then declines, halving every 4.3 years. There were no direct measurements of historic radon levels. A conservative estimate based on measurements taken since 1969 by the National Radiological Protection Board and the Mines and Quarries Inspectorate is that the annual dose to an underground worker was about 10 working level months (WLM). Given this assumption, the risk/exposure slope implied by the present data, and the model fitted to it, was somewhat lower than that given in the fourth Committee on the Biological Effects of Ionisation Radiation (BEIR IV) report (about 40% lower for lifetime exposures). The present data also imply different risks depending on the age at exposure, with relatively higher lifetime risks for exposure at older ages, and relatively lower risks for exposures at younger ages. In conclusion, there was a clear relation between exposure to radon and death from lung cancer. The relative risk of lung cancer due to exposure to radon was not constant in cessation of exposure. The lifetime excess risk of lung cancer implied by these data for 40 years exposure at the current statutory limit of four WLM a year starting at age 20, was about 8% (79 excess deaths per 1000 exposed), assuming average smoking habits among the exposed workers. Control of dust concentrations in the mines has substantially reduced--and may have eliminated--direct mortality from silica related disease. PMID- 2223660 TI - Age, sex, and region adjusted concentrations of chromium and nickel in lung tissue. AB - Chromium (Cr) and nickel (Ni) concentrations were measured in lung tissue from 110 random necropsies by means of atomic absorption spectrometry. The subjects originated from the Ruhr district (Bochum (71 cases) and Dortmund (16 cases) areas), which has been defined as a particular pollution area with locally high Cr and Ni emissions, and from Munster and vicinity (23 cases). The Cr and Ni concentrations in lung tissue of the subjects from the Ruhr district (3.09 (SD 2.99) micrograms Cr/g, 0.65 (SD 0.94) micrograms Ni/g dry weight of lung) were 4.8 and 2.8 times higher than those from Munster (0.66 (SD 0.49) micrograms Cr/g, 0.17 (SD 0.11) micrograms Ni/g dry weight of lung). Concentrations of Cr and Ni in men were twice those in women. All data showed an age dependent increase of Cr and Ni in the lung (about 2.4% a year for Cr and 3% a year for Ni) and Cr and Ni values showed a high correlation (r greater than or equal to 0.9). Thus it was possible to calculate age, sex, and region adjusted expected values of pulmonary Cr and Ni concentrations, and to identify the difference between expected and observed values. This might be helpful to interpret measurements in individual cases and in epidemiological studies. With this procedure the six cases of bronchial carcinoma in the series were shown to have pulmonary Cr and Ni concentrations that were mostly well above the predicted values, and it was possible to give a rough estimate of the degree of deviation. PMID- 2223661 TI - Toxic risks from inhalation of bacterial endotoxin. AB - A potential risk for workers exposed to inhalation of endotoxin, as well as the primary tissue changes, is the possibility of subsequent development of adult respiratory distress syndrome. Accordingly, hamsters were administered one hour aerosols of Enterobacter agglomerans and allowed to rest for six hours to produce maximum microlesions in the lung. One hour before this peak, the animals were injected intravascularly with the same suspension used in the aerosol. After one hour the animals were killed and bronchopulmonary lavages were made for analysis of free lung cells. As anaesthesia alone has been reported to be one of the operative procedures that enhance the effect of previous exposure to endotoxin, controls had to include sham anaesthesia with no intravascular injection. Endotoxin inhalation induced significant increases in total number of pulmonary leucocytes, mostly neutrophils, but with a concomitant relative decrease in number of alveolar macrophages. These polymorphonuclear neutrophils are not seen in morphometric analysis of the alveoli. Of greater interest was the large increase in erythrocytes suggesting pulmonary haemorrhages. Such changes were not due to intravenous bacterial alone, and were only significant when the bacteria were inhaled. Taken together with the other known inflammatory effects of inhaled bacteria or bacteria containing endotoxin, such inhalation in an occupational setting constitutes an increasingly recognised risk for workers. PMID- 2223662 TI - Effect of alkali treatment on physiological activity of cotton condensed tannin. AB - Cotton dusts contain condensed tannins and endotoxins, which are suspected of contributing to the development of acute and chronic biological responses in some cotton textile mill workers. Condensed tannin extracted from cotton dust was coated on to cellulose powder, and the tannin coated powder was treated with an alkali solvent system previously developed to reduce the endotoxin content and pulmonary toxicity of cotton dust. Physiological activities of the dusts and powders were compared by assaying the production of the arachidonic acid metabolites prostaglandin F2 alpha (PGF2 alpha), thromboxane A2 (TxA2) (the precursor to thromboxane B2 (TxB2], leukotriene C4 (LTC4), and prostaglandin E2 (PGE2) by guinea pig pulmonary cells obtained by lung lavage. Cotton dust stimulated the pulmonary cells to produce a total of 29 pg metabolites per 10(6) cells. Production of metabolites by cells stimulated with tannin coated cellulose powder was reduced to 8.3 pg/10(6) cells. Alkali treatment of the tannin coated cellulose powder resulted in a further decrease in its ability to stimulate the cells, producing 3.5 pg metabolites per 10(6) cells. The ability of the dusts and powders to stimulate production of metabolites of arachidonic acid by pulmonary cells from guinea pigs was highly correlated with tannin content of the materials, but not with endotoxin content as measured by the Limulus amoebocyte lysate (LAL) assay. PMID- 2223663 TI - Neuropsychiatric symptoms among welders exposed to neurotoxic metals. AB - Neuropsychiatric symptoms in 65 welders exposed to aluminium and 217 railroad track welders were studied with the aid of a previously validated questionnaire. Semiquantitative data on exposure to the metals aluminium, chromium, lead, manganese, and nickel were also recorded by questionnaire. Logistic regression was employed to study the relation between exposure and the prevalence of symptoms. Welders exposed to aluminium, lead, or manganese for a long period had significantly more neuropsychiatric symptoms than welders not exposed to these metals. The results indicate that detailed psychometric studies should be performed on welders exposed long term to specific metals as such exposures might affect their nervous system. PMID- 2223664 TI - Reduced vibration perception in right hands of normal subjects: an acquired abnormality? PMID- 2223666 TI - [Precious metal onlays]. AB - In prosthetics, various options are available to the orthodontist for repairing dental arches. The basic choice is between full crowns and partial crowns. Full crowns are primarily indicated for aesthetic reasons, in order to correct tooth axes and in cases of recurrent caries. Partial crowns in precious alloys are indicated when the need is not essentially aesthetic. They continue today to offer advantages in restoring posterior teeth. Because of their supragingival limits, they alleviate periodontal problems and preserve tooth structure. PMID- 2223665 TI - Risk assessment of leukaemia and occupational exposure to benzene. PMID- 2223668 TI - [Preparations for anterior composites]. AB - This paper sets forth and discusses the various preparations used in aesthetic restoration of anterior teeth with composite resins. The clinical description of contours involves treatment of class III and IV carious lesions and correction of aesthetic imperfections which justify resorting to direct techniques of cosmetic dentistry. PMID- 2223667 TI - [Bonding of ceramic onlays. The effect on contour form]. AB - Ceramic onlays have come into much wider use and experience has led to gradual modification of preparation contours. The aim was to improve two complementary aspects, aesthetics and mechanical strength. The use of ceramics to rebuild cusps enhances the structures' mimetic effect and mechanical qualities. If an isthmus exists connecting the occlusal and proximal cavities, it must be enlarged; if not, none must be created. The use of bonded ceramic overlays offers an original therapeutic result. They are indicated in order to even out occlusal patterns. PMID- 2223669 TI - [Ceramic bonded veneers. Toward a minimal prosthesis]. AB - For years, odontology for aesthetic purposes meant significant tissue mutilation. Now, with bonded porcelain veneers, it is possible to achieve both an aesthetic result and a veneer preparation while restoring the function of anterior teeth. The clinical forms of such thin bonded restorations may vary considerably, from a simple veneer to a 3/4 crown. Although after five years of experience, prosthetic "enamelling" appears to be totally reliable, only long-term clinical results will determine the fatigue of thinly applied ceramics. PMID- 2223670 TI - [Amalgams. Traditional and modern]. AB - The amalgam continues to be the most widely used material for durable restoration of decayed bicuspids and molars. After a discussion of this material's relative drawbacks, the author describes the restoration possibilities now offered by the advanced high-copper alloys available today. The latest developments involve both "conservative" preparations and extensive pre-prosthetic occlusal restorations. PMID- 2223671 TI - [Marginal adaptation of posterior composites. A complex clinical problem]. AB - In this article, the authors deal with the problem of marginal fit for posterior composites, where direct class-II aesthetic restoration is involved. For different materials, they analyse and discuss the influence of their physicochemical properties, the contour of preparations, and composite handling. Three types of clinical cases are described: preparation using the tunneling technique, adhesive preparation, conventional preparation. PMID- 2223672 TI - [Coronal filling biomaterials. Criteria for selection]. AB - The aim of this paper is to assess filling biomaterials according to specification criteria, the foremost of which is the respective ability of each to form a tight seal along cavity walls. Their direct or indirect (cementing or bonding) adhesive potential is the determining factor in their durability and the biocompatibility of the restoration achieved. Gold inlay alloys and amalgams appear as yet to be the most reliable and well-tolerated biomaterials for posterior restorations. For filling small cavities in the anterior sector, microfilled composites are clearly indicated; bonded porcelain, while not yet validated over time, would seem to be a good alternative for more extensive restorations. PMID- 2223674 TI - Regional Anesthesia. Volumes 1-5. October-December 1976--October-December 1980. Reprinted. PMID- 2223673 TI - [Composite resin inlays. Convincing solution or uncertain compromise?]. AB - This is a report on the authors' clinical experience years of using laboratory composites. They describe the contours of composite resin preparations for inlays, discuss the advantages drawbacks of such restorations and provide limited indications. The illustrations also involve specific clinical cases. PMID- 2223675 TI - Rest in hospital and twin pregnancy. PMID- 2223676 TI - The effects of hospitalization for rest on fetal growth, neonatal morbidity and length of gestation in twin pregnancy. AB - OBJECTIVE: To test whether a policy of hospitalization for bed rest, from 28-30 weeks gestation until delivery, lengthens the duration of gestation, improves fetal growth and decreases neonatal morbidity in twin pregnancy. DESIGN: A randomized controlled trial. SETTING: Harare Maternity Hospital, Zimbabwe. SUBJECTS: 118 women with an uncomplicated twin pregnancy between 28 and 30 weeks gestation. INTERVENTION: Hospitalization for bed rest. Encouraged to rest in bed as much as possible, although voluntary ambulation was allowed. MAIN OUTCOME MEASURES: Gestational age at delivery and number of infants delivered preterm (less than 37 weeks); birthweight and number of small-for-gestational age (SGA) infants; neonatal morbidity was assessed by number of infants requiring admission to the neonatal unit and the length of stay. RESULTS: There was no effect on duration of gestation or the occurrence of preterm delivery. Mean birthweight was greater in the hospitalized group (t = -2.28, df 234, P = 0.02) and there were fewer SGA infants (OR 0.57, 95% CI 0.33-0.96). No differences were found in neonatal morbidity. CONCLUSIONS: Hospitalization for bed rest does not prolong pregnancy but can improve fetal growth, although this was not reflected in improved neonatal morbidity. Whether twin fetal growth can be enhanced similarly in other populations should be investigated. PMID- 2223677 TI - Failure to prevent preterm labour and delivery in twin pregnancy using prophylactic oral salbutamol. AB - A double blind, controlled study was performed to see whether the use of prophylactic oral salbutamol would reduce the incidence of preterm labour in twin pregnancy. Of the 144 women studied, 74 took salbutamol and 70 placebo. No difference was found in the length of gestation, birthweight or fetal outcome, although fewer babies suffered from respiratory distress syndrome in the salbutamol group. Women did not experience troublesome side-effects from salbutamol. PMID- 2223678 TI - The relative risks of caesarean section (intrapartum and elective) and vaginal delivery: a detailed analysis to exclude the effects of medical disorders and other acute pre-existing physiological disturbances. AB - OBJECTIVE: To compare maternal mortalities attributable to vaginal delivery, elective caesarean section (CS) and intrapartum CS. DESIGN: The number of deaths associated with each method of delivery was ascertained among unselected and among low-risk women by detailed retrospective review of the case-notes of women who died after delivery. The frequency of each method of delivery throughout the study period was ascertained from the computer database and enhanced by analysis of the case-notes of unselected groups of women. SETTING: The Peninsula Maternity Services (Cape Town) during the years 1975-1986 inclusive. SUBJECTS: A total of 108 maternal deaths arising from 263,075 maternities provided accurate information. The relative frequency of vaginal and abdominal delivery was determined from the computer database. The ratio of elective CS to emergency prepartum CS to intrapartum CS was obtained by review of the first 200 operations in the years 1975, 1977, 1979, 1982 and 1984. MAIN OUTCOME MEASURES: (i) Mortality rates associated with the different methods of delivery in unselected women and in women who were healthy before surgery; (ii) mortality rates apparently attributable to the method of delivery. RESULTS: The overall relative risk of mortality associated with caesarean section compared with vaginal delivery was 7 decreasing to 5 after the exclusion of women with medical or life threatening antenatal complications (eg, haemorrhage, hypertension). The relative risk associated with intrapartum compared with elective sections was 2.3 decreasing to 1.4 after the exclusion of women with medical disorders or life threatening complications. The relative risk of maternal mortality which was apparently attributable to intrapartum compared with elective sections was 1.7. However, the 95% confidence intervals of these values, even from this large data set, are wide. Nevertheless, these rates are in broad agreement with an approximation derived from the British confidential enquiries into maternal deaths. CONCLUSION: The attributable relative mortalities of caesarean section compared with vaginal delivery and intrapartum compared with elective caesarean section are lower than the overall relative mortalities of these modes of delivery and are approximately 5:1 and 1.5:1 respectively. These data are crucially important in the decision to recommend elective caesarean section compared with trial of labour. PMID- 2223679 TI - Idiopathic thrombocytopenic purpura in pregnancy: a randomized trial on the effect of antenatal low dose corticosteroids on neonatal platelet count. AB - OBJECTIVE: To determine the efficacy of antenatal low dose oral betamethasone in preventing neonatal thrombocytopenia and/or bleeding in infants of mothers with idiopathic thrombocytopenic purpura (ITP). SETTING: Hospital department of obstetrics and gynaecology, referral centre. PATIENTS: 41 pregnancies in 38 women were randomized. The results of 13 pregnancies were considered non-assessable. The final analysis involved 14 in the betamethasone group and 14 in the non treatment group. All fulfilled the criteria for ITP. INTERVENTIONS: The treated group received 1.5 mg betamethasone orally per day, from day 259 till day 273 and 1 mg from day 273 till delivery. MAIN OUTCOME MEASURES: Effects of treatment were assessed in terms of maternal platelet counts after the first trimester and neonatal platelet counts at birth and the first week of life and neonatal bleeding episodes. RESULTS: There were no significant differences in neonatal platelet counts at birth. Two infants in the betamethasone group and one in the untreated group had a severe thrombocytopenia either at birth or during the first week of life (less than 50 x 10(9)/l). Seven infants in the betamethasone group and six in the non-treatment group had a mild thrombocytopenia. The overall frequency of neonatal thrombocytopenia was similar: 64% in the betamethasone group and 57% in the untreated group (95% CI of the true difference: -43.5% to +29.5%). There was also no significant difference in neonatal bleeding episodes. CONCLUSIONS: Low-dose betamethasone in pregnant women with ITP does not prevent thrombocytopenia or bleeding in their newborn infants. PMID- 2223680 TI - Normal early pregnancy: serum hCG levels and vaginal ultrasonography findings. AB - Vaginal sonography and determination of serum hCG levels were carried out in 22 healthy pregnant women every 2 to 4 days after the first positive pregnancy test until a living fetus was observed. Gestational age was calculated from the day of ovulation, assessed by LH surge or hCG administration, plus 14 days. A gestational sac of 1-3 mm was detected at a mean (SEM) of 31.2 (0.2) days of gestation (range 30-33 days). The corresponding mean hCG level was 730 iu/l (30) and the range 467-935 iu/l (International Reference Preparation). The yolk sac was detected at a mean of 36.0 (0.2) days, range 34-38 days, at a mean hCG level of 4130 iu/l (370), range 1120-7280 iu/l. Fetal heart motion was visible at a mean of 41.1 (0.3) days, range 39-43 days and the corresponding mean hCG level was 12,050 iu/l (1240), range 5280-22,950, iu/l. The yolk sac and the fetal heart motion were always seen when the sac exceeded 10 and 18 mm in mean diameter, respectively. PMID- 2223681 TI - Diagnosis of ectopic pregnancy by vaginal ultrasonography in combination with a discriminatory serum hCG level of 1000 IU/l (IRP) AB - The diagnostic value of vaginal sonography in combination with a discriminatory serum hCG level of 1000 iu/l (International Reference Preparation) was tested prospectively in 200 pregnant women suspected of having an ectopic pregnancy. An ectopic pregnancy was diagnosed in 68 women (34%), a miscarriage in 56 (28%) and a normal pregnancy in 76 (38%). On admission, an intrauterine sac was seen in 89% of the intrauterine pregnancies, but in none of the ectopic pregnancies. Detection of an adnexal mass separate from the ovaries was diagnostic of ectopic pregnancy with a sensitivity of 93%, a specificity of 99%, a positive predictive value of 98% and a negative predictive value of 96%. In 19 patients (9%) the initial sonogram was non-diagnostic and the final diagnosis was obtained after a repeated scan within 6 days. Five of these women had an ectopic pregnancy, 12 a miscarriage and two a normal pregnancy. On admission the hCG level exceeded 1000 iu/l in 77% of all patients and in 67% of those with ectopic pregnancies. In patients with an initial level exceeding 100 iu/l, an intrauterine sac was found in all the intrauterine pregnancies but in none of the ectopic pregnancies. The use of this threshold in combination with sonographic detection of an adnexal mass was diagnostic of ectopic pregnancy with a sensitivity of 97%, a specificity of 99%, a positive predictive value of 98% and a negative predictive value of 98%. PMID- 2223682 TI - Randomized comparison of routine vs highly selective use of Doppler ultrasound and biophysical scoring to investigate high risk pregnancies. AB - OBJECTIVE: To compare routine versus highly selective use of Doppler ultrasound and biophysical scoring in higher risk pregnancy. DESIGN: A pragmatic randomized trial. SETTING: St James's University Hospital, Leeds. SUBJECTS: 500 pregnant women at high risk of intrauterine growth retardation or still birth. INTERVENTIONS: Regular monitoring with biophysical profile assessment and Doppler velocity waveform recording in umbilical and uteroplacental arteries. Results immediately available to clinicians. MAIN OUTCOME MEASURES: Gestational age at delivery, obstetric intervention rates and short-term neonatal morbidity. RESULTS: Risk factors were distributed very evenly between the 250 patients in the study and control groups respectively. A total of 902 biophysical profile and Doppler assessments were done in the 250 study group patients and only in 12 patients in the control group. In the study group, absent end-diastolic flow was found in only 2.7% of all 902 measurements. A persistently abnormal biophysical score was always associated with absence of end-diastolic flow. The mean gestational age at induction of labour was statistically and clinically similar in the two groups and there was no overall statistically significant difference in intervention rates between the two groups. There was a statistically significant lower frequency of depressed 5-min Apgar scores in the study group. Serious neonatal morbidity was also statistically significantly more common in the control group than in the study group. CONCLUSIONS: The use of Doppler ultrasound in higher risk pregnancies does not lead to an increase in iatrogenic preterm delivery. The total rate of positive tests on Doppler ultrasound is very low and persistently abnormal biophysical scores are unlikely to be found in patients where umbilical end-diastolic blood flow is present. Surrogate measures for fetal damage seem to be improved when clinicians have access to Doppler ultrasound assessments. PMID- 2223683 TI - Hormone implants and tachyphylaxis. AB - The serum oestradiol levels of 1388 women treated with hormone implants at a menopause clinic were reviewed in 1988. Thirty-eight (3%) were found to be above 1750 pmol/l. Of these 38 women with supraphysiological oestradiol levels 23 had started therapy for menopausal symptoms and 15 for the premenstrual syndrome (PMS). Of the 23 women treated for menopausal symptoms 11 had a history of psychiatric referral for depression and nine had undergone a surgical menopause. Nine of the 15 women with PMS had a history of psychiatric referral for depressive symptoms. We conclude that the women who attain supraphysiological levels of oestradiol on implant therapy have a high frequency of psychopathology or surgical menopause and may require higher oestradiol levels for adequate control of symptoms. PMID- 2223685 TI - Serum CA 125 levels during the menstrual cycle. AB - Serum concentrations of CA 125 were measured in different phases of the menstrual cycle in 16 women with ovulatory and 12 women with anovulatory cycles. CA 125 levels were significantly elevated during menstruation in both groups. In women with anovulatory cycles, but not in those with ovulatory cycles, CA 125 levels were already increased in the premenstrual phase. A negative correlation was found between serum CA 125 and progesterone concentrations in the premenstrual phase of the cycle. We suggest that premenstrual elevation of serum CA 125 in women with anovulatory cycles is related to premature endometrial vascular changes which are the result of the low serum progesterone concentration leading to insufficient endometrial control. Thus the effect of progesterone seems to be indirect rather than a direct effect on CA 125 synthesis. When the CA 125 assay is used for diagnosis of cancer, sampling should not be done immediately before or during menstruation because the physiological elevation of the CA 125 levels may give false positive results. PMID- 2223684 TI - A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. AB - Age, ultrasound score, menopausal status, a clinical impression score and serum CA 125 level were assessed to see how they could best distinguish between patients with benign (n = 101) and malignant (n = 42) pelvic masses. Each criteria used alone provided statistically significant discrimination. The most useful individual criteria were a serum CA 125 level of 30 U/ml (sensitivity 81%, specificity 75%) and an ultrasound score of 2 (sensitivity 71%, specificity 83%). Three criteria could be combined in a risk of malignancy index (RMI) which is simply calculated using the product of the serum CA 125 level (U/ml), the ultrasound scan result (expressed as a score of 0, 1 or 3) and the menopausal status (1 if premenopausal and 3 if postmenopausal). This index was statistically virtually as effective a discriminant between cancer and benign lesions as more formal methods. Using an RMI cut-off level of 200, the sensitivity was 85% and the specificity was 97%. Patients with an RMI score of greater than 200 had, on average, 42 times the background risk of cancer and those with a lower value 0.15 times the background risk. PMID- 2223686 TI - The effect of abdominal surgery on the serum concentration of the tumour associated antigen CA 125. AB - The CA 125 assay is used to monitor the course of disease in women with adenocarcinoma of the genital tract. We measured serum CA 125 levels longitudinally in three different groups of patients who had normal serum CA 125 levels (less than or equal to 16 U/ml) before extensive intraperitoneal abdominal surgery (group 1, second-look laparotomy in 28 women with ovarian cancer; group 2, radical hysterectomy in 42 patients with cervical cancer; group 3, 13 men and one woman who had aortic surgery for atherosclerotic occlusive disease or aneurysm formation). Following surgery, rising serum CA 125 levels were observed in 69 out of the 84 patients (82%), irrespective of the primary diagnosis, type of operation or sex. The highest levels were found during the second week after the operation (range 3-336 U/ml) and decreased gradually thereafter, to become normal at 8 weeks after surgery. It was concluded that abdominal surgery interferes with the specificity of CA 125 as a tumour marker during the early postoperative period. PMID- 2223688 TI - Double survival despite cord entwinement in monoamniotic twins. Case report. PMID- 2223687 TI - Haemostatic changes during continuous oestradiol-progestogen treatment of postmenopausal women. AB - To identify changes in haemostatic balance during continuous oestradiol progestogen treatment, 60 postmenopausal women with climacteric complaints, mean age 55.4 years (range 44-68) were randomly allocated to receive one of four hormone replacement regimens for one year. All four formulations were administered daily and continuously, each contained 2 mg of 17 beta-oestradiol in combination with either norethisterone acetate, 1 mg (group A) or 0.5 mg (group B) or megestrol acetate, 5 mg (group C) or 2.5 mg (group D). No significant changes occurred during treatment within or between the groups in platelet count, fibrinogen and 2-antiplasmin. Activated partial thromboplastin time was shortened (P less than 0.05) in group D and a decline in factor VII activity and antigen (P less than 0.001) and in ATIII activity (P less than 0.05) was noted in group A. Protein C tended to decline in all treatment groups but statistically significant changes were noted only in groups A and C. Two women developed crural thrombosis during the observation period. PMID- 2223689 TI - Mucinous ascites associated with rupture of benign ovarian teratoma. Case report. PMID- 2223690 TI - Non-immune hydrops in trisomy-18. Diagnosis by vaginosonography and chorionic villus sampling in the first trimester. Case report. PMID- 2223691 TI - Fetal macrosomia in potential diabetics with normal oral glucose tolerance: a case control study. PMID- 2223692 TI - Early identification of placenta praevia. PMID- 2223693 TI - Pipelle: a more acceptable technique for outpatient endometrial biopsy. PMID- 2223694 TI - The obstetric forceps--are we using the appropriate tools? PMID- 2223695 TI - Change in ovarian arterial compliance during the human menstrual cycle assessed by Doppler ultrasound. PMID- 2223696 TI - Cesarean section for the birth of the second twin. PMID- 2223697 TI - Fluorosilicone oil for retinal detachment. PMID- 2223699 TI - Intraocular pressure changes and postural changes of intraocular pressure in experimentally induced Hansen's disease of rhesus, mangabey, and African green monkeys. AB - In our long term evaluation of patients with Hansen's disease we have frequently found reduction of their intraocular pressure. Furthermore, we noted changes in their intraocular pressure on change of posture. To determine if these changes have any significance we measured the intraocular pressures of 24 experimentally infected and 39 control monkeys in both sitting and reclining positions. We found significant reduction of intraocular pressure in 66.7% compared with controls in the sitting position, and a significant increase in intraocular pressure in 79% when checked first in the sitting then in the reclining position. We offer a possible pathophysiological explanation as to why the changes occur. PMID- 2223698 TI - Fluorosilicone oil in the treatment of retinal detachment. AB - We evaluated the use of a heavier-than-water fluorinated silicone oil in the treatment of 30 selected cases of complicated retinal detachment from January 1988 to July 1989. Proliferative vitreoretinopathy grade C-2 or greater accounted for 19 cases, proliferative diabetic retinopathy with traction detachment for two cases, giant retinal tears five, ruptured globe with retinal detachment two, massive choroidal effusion with retinal detachment one, and acute retinal necrosis with retinal detachment one. Initial retinal reattachment was achieved in all cases. Complications included redetachment seven (23%), cataract six (75% of phakic patients), raised intraocular pressure four (13%), hypotony four (13%), keratopathy three (10%), uveitis-synechia formation three (10%), phthisis two (3%), choroidal haemorrhage one (3%), and vitreous haemorrhage one (3%). Postoperative visual acuities with at least six months' follow-up range from no light perception to 20/50, with seven patients (23%) 20/400 or better. PMID- 2223700 TI - A survey of the initial referral of children to an ophthalmology department. AB - We report on a survey of the referral of 525 children making their first visit to an ophthalmology department. Information was gathered by interviewing the parents and reviewing the case notes. Parents and relatives initiated the referrals in 223 cases (42%) and health visitors initiated a further 123 cases (23%). General practitioners were rarely the first to notice a condition, though they played a major part in the subsequent referral process. Of 556 reasons for referral squint was the most important (319 cases, 57%), followed by poor vision (106 cases, 19%). There were 44 confirmed cases of amblyopia, of which 15 (34%) were not detected until the child was aged 5 years or over. The overall accuracy of referral was 66% (367 reasons for referral confirmed). In 109 cases (21%) the child was found to be normal. Parents and relatives first noticed 54% of cases of confirmed squint but only 15% of the cases of poor vision. Health professionals, especially health visitors, were of great importance in first detecting poor vision. PMID- 2223702 TI - Aqueous humour and serum zinc and copper concentrations of patients with glaucoma and cataract. AB - Serum and aqueous humour zinc and copper concentrations of 44 patients with glaucoma and cataract were determined. Serum values were found within normal ranges. The highest mean copper concentration was seen in the glaucoma group. In addition there was a significant negative correlation between the aqueous humour levels of zinc and copper in patients with glaucoma. It was concluded that an increased copper value together with a low zinc value might be of importance in patients with glaucoma. PMID- 2223701 TI - Biometry of the crystalline lens in early-onset diabetes. AB - Lenticular biometry on non-cataractous lenses has been studied by means of Scheimpflug photography and digital image analysis in 153 patients with early onset insulin-dependent diabetes and 153 non-diabetic controls. Anteroposterior axial lens thickness, cortical thickness, nuclear thickness, anterior and posterior lenticular curvatures, and anterior chamber depth were assessed. Highly significant differences between the lenses of the diabetic subjects and non diabetic controls were found. After the effect of age had been accounted for within the diabetic subgroup, diabetic duration was found to be a highly significant determinant of lens dimensions, such that age-related dimensional changes for various biometric parameters were accelerated by between 52% and 121% after the onset of diabetes. Because the diabetic duration of the early-onset diabetic subjects studied in this work was accurately known, this report is the first in which a precise assessment of the effect of 'true' diabetic duration on lens biometry has been possible. PMID- 2223703 TI - Topical timolol and serum lipoproteins. AB - Oral timolol taken for the treatment of systemic hypertension has been shown to affect adversely serum lipoprotein levels. In a 15-week study on 19 patients topical timolol therapy for raised intraocular pressure was found to have no significant adverse effect on serum lipoprotein levels. This is reassuring in view of the large number of patients on this form of long term therapy, and selection of the type of beta blocker to use should not be influenced by lipid changes associated with the oral form of the drug. PMID- 2223704 TI - Haemorheological changes in patients with retinal vein occlusion after isovolaemic haemodilution. AB - In 83 patients with central retinal vein occlusion and branch vein occlusion we measured the haematocrit (HCT), plasma viscosity (PV), red cell aggregation (RCA), red cell filterability (RCF) and apparent whole blood viscosity (WBV). A control group (n = 41) was matched for sex, age, and cardiovascular risk factors. Measurements were performed before and after treatment with isovolaemic haemodilution (IHD). We found no significant differences between patients with retinal vein occlusion (RVO) and control subjects in haematocrit, plasma viscosity, red cell aggregation, and red cell filterability and no increased whole blood viscosity in the patient group. Patients with ischaemic retinal vein occlusion and non-ischaemic retinal vein occlusion did not show different haemorheological parameters either. After treatment with haemodilution, only the haematocrit and whole blood viscosity were significantly decreased, and there were no changes in plasma viscosity, red cell aggregation or red cell filterability. PMID- 2223705 TI - Pupillary responses in amblyopia. AB - Relative afferent pupillary defects (RAPD) were detected in 32.3% of patients with amblyopia by a modification of the swinging flashlight test and the synoptophore. After consideration of various clinical investigations the significant factors identified in patients showing a RAPD were: anisometropia, early age of onset where strabismus was present, level of visual acuity following treatment, longer period of occlusion therapy. These points bear similarities to the results of pattern electroretinograms (PERG) in amblyopes, and the possibility of the causative defect being at ganglion cell level is discussed. The effect of occlusion treatment cannot be predicted from the presence or absence of a RAPD. PMID- 2223706 TI - The electroretinogram in minimal diabetic retinopathy. AB - The pattern and diffuse flash electroretinograms were measured in 20 normal subjects and 40 diabetic patients who had either normal fundi or microaneurysms only. The amplitudes of the pattern electroretinogram were found to be similar in both normals and diabetics. In the case of the flash electroretinogram the diabetic patients showed a division into two main groups. One group was not dissimilar to the group of normal subjects, while the second group showed hypernormal amplitudes. No explanation could be given, from the data collected, for this subdivision, though it is suggested it might reflect the degree of metabolic disturbance. PMID- 2223707 TI - Supply of corneal tissue in the United Kingdom. PMID- 2223709 TI - Linear scleroderma associated with ptosis and motility disorders. AB - A case is reported in which an 11-year-old girl developed progressive ptosis and a subsequent motility disorder of the right eye. The diagnosis linear scleroderma en coup de sabre was established. Atrophy of the upper levator palpebral and superior rectus muscle could be shown on CT scan. PMID- 2223708 TI - Multifocal posterior uveitis: clinical and pathological findings. AB - A pathological study was performed on the necropsy eyes of a 59-year old-woman who had suffered for nine years from multifocal posterior uveitis. The disease had been controlled by steroid therapy with good preservation of visual function. Extensive investigation did not reveal the aetiology. On macroscopic examination numerous focal lesions with various degrees of pigmentation were observed scattered across the fundi. These lesions were studied by light and electron microscopy and immunohistochemistry. There was ongoing chorioretinal inflammation in the foci, producing destruction of Bruch's membrane, the retinal pigment epithelium (RPE), and the outer retina. The focal scars showed migration of RPE and glial cells and neovascularisation. Capillary and venule endothelial cells were swollen at the inflammatory sites. Attempts to establish a cause for this condition were unsuccessful. PMID- 2223710 TI - Homocystinuria presenting as central retinal artery occlusion and longstanding thromboembolic disease. AB - A case of central retinal artery occlusion in a patient with a 10-year history of unexplained thromboembolic disease due to a secondary hypercoagulable state is presented. Ophthalmological examination led to the final diagnosis. PMID- 2223711 TI - Chickenpox chorioretinitis. AB - Chickenpox infection in an adult was complicated by peripheral chorioretinitis and treated with oral acyclovir. Similarities of this case to the recently proposed mild type of acute retinal necrosis syndrome are discussed. PMID- 2223713 TI - Lobular pattern of choriocapillaris in pre-eclampsia with aldosteronism. AB - We report a case of geographic or mosaic pattern yellowish opaque foci in the left eye of a 36-year-old woman who suffered from severe pre-eclampsia. Though the geographic lesions resulted in chorioretinal atrophy, the mosaic lesion led to no significant atrophy. These two findings were both diagnosed as manifestations of choroidal ischaemia, the former due to choroidal artery occlusion, the latter to transient insufficiency of choroidal circulation, which reflects the lobular pattern of the choriocapillaris. PMID- 2223712 TI - Choroidal osteoma (osseous choristoma): an atypical case. AB - A case of choroidal osteoma presenting in a 22-year-old girl is reported. The tumour, unilateral and in a juxtapapillary site, appeared markedly elevated on the retinal plane, not flat or slightly elevated as in previous reports. Visual acuity was not affected, and there was a complete absence of subjective symptoms. Echography, fluorangiography, computerised tomography, and visual field tests were performed. Echography is the best method for identifying and differentiating this lesion from a malignant tumour. PMID- 2223715 TI - Diabetes and retinal function. PMID- 2223714 TI - Compact field charts. PMID- 2223716 TI - [The current stage of thoracic surgery]. PMID- 2223718 TI - [The integration of antitubercular treatment into the activities of 3 rural medical dispensaries in the area of the Constanta Phthisiology Office]. PMID- 2223717 TI - [The recovery of work capacity within the framework of short-term antitubercular chemotherapy]. AB - The authors compare the results of chemotherapy reflected in the proportion of recoveries of work capacity and the number of retired persons in two groups of patients--one including 102 cases treated between 1970 and 1971 by a 3/6 regimen, and another one including 91 patients treated in 1986 by a modern intensive 3 + 3 regimen. The data indicate better results with the 1986 lot as compared with the 1970-1971 lot. In the 1986 group there were no fatalities and the persons that recovered their work capacity represented 90.1% of the total. By contrast, in the group treated between 1970 and 1971 there were two fatalities and only 84.3% of all the patients did recover the work capacity. The number of retired persons decrease from 11.7% in the first group to 7.7% in the second. Temporary incapacity decreased from an average of 321 days to an average of 267 days in the second group. All these results were obtained by shortening the treatment from an average of 9 months to an average of 6 months. PMID- 2223719 TI - [The efficacy of the intensive, short-duration chemotherapy of patients with cavitary pulmonary tuberculosis]. AB - This study was carried out on 100 cases of cavitary pulmonary tuberculosis in patients eliminating tuberculosis bacilli, as noted at microscopic study. The treatment included four drugs (RHSZ) in 95 case, and 3 drugs in the remaining patients. All the treatments were tailored to individual needs. The duration of chemotherapy was of 6 months in 62 cases. It was prolonged to 9 months in 33 cases and to 12 months in 5 cases. In 81 patients the drugs were applied regularly. The results have demonstrated that at 6 months negative cultures were obtained in 98 patients although the excavations were closed in only 55 cases. At 9 months all the patients were negative but excavations were closed in only 71. Suppression of elimination of bacilli was achieved in 99 of the cases at 12 months, but the excavations were closed in only 92 of the patients. Ninety-nine patients were investigated after 2.5-3.0 years. Five of them were again positive, 94.5% were negative and the excavations were closed in 91.9%. The importance of the cavitary score is discussed with regard to the risk of renewed positivity, and an association is recommended of surgical collapsing and exeresis at the right time. PMID- 2223720 TI - [The involvement of the respiratory apparatus in leukemias]. AB - In 13 cases of leukemia, different clinical forms showed pleuropulmonary and mediastinal lesions consisting in: mediastinal-hilar adenopathies without the parenchyma involvement (2 cases), with involvement of the pulmonary parenchyma (6 cases) and only one case of pulmonary lesions without adenopathies. In 3 cases leukemia overlapped pulmonary TB, TB sequela (2 cases) or active-evolutive TB (1 case). One case developed to bronchopulmonary neoplasm. While the treatment of parenchymatous complications, appeared by nonspecific infections, and of the single case of active tuberculosis proved adequate, the ganglionic-mediastinal lesions continued their acute or chronic unfavourable evolution. PMID- 2223721 TI - [The evolution of pulmonary ventilation under conditions of occupational exposure to irritant vapors]. PMID- 2223722 TI - [Immunopathogenic processes in infectious pulmonary diseases]. PMID- 2223723 TI - [Toxic pulmonary and neuronal reactions to nitrofurantoin]. PMID- 2223724 TI - [Tuberculosis localized in the skull bones in a child]. AB - A case is presented, of a child aged 2.8 years with tumor-like formations in the parietal and the frontal bones, showing lacunar lesions on the radiography of the skull. This case raised a large number of hypotheses concerning the etiologic diagnosis of the lacuna lesions. Histologic investigations showed that lesions were due to tuberculosis of the skull bones. In this case probability and certitude criteria were present supporting this diagnosis. PMID- 2223725 TI - [Biopsy of the cervical lymph nodes in the diagnosis of sarcoidosis]. PMID- 2223726 TI - [Liver determinations in sarcoidosis]. PMID- 2223727 TI - [Hepatic sarcoidosis with portal hypertension]. PMID- 2223728 TI - [The role of the lymphocytes in sarcoidosis]. PMID- 2223729 TI - [The role of the macrophages in sarcoidosis]. PMID- 2223730 TI - [The involvement of eicosanoids in the pathogenesis of inflammatory granuloma]. PMID- 2223732 TI - [Granulomatous disorders mimicking sarcoidosis]. PMID- 2223731 TI - [The role of oxygen metabolites in sarcoidosis]. PMID- 2223733 TI - [The intradermal tuberculin test and the Kveim-Siltzbach test in sarcoidosis]. PMID- 2223734 TI - [The coagulation and fibrinolysis systems in sarcoidosis]. PMID- 2223735 TI - Dietary recommendations: how do we move forward? PMID- 2223736 TI - Linear programming and pediatric dietetics. AB - The composition of 500 foods has been stored in a computer in order to analyse a child's diet. The methodology of operations research is applied to a very simple problem: a diet with only two foods. The geometrical representation of the 'feasible region' and of the 'objective function' is illustrated. One of the analytical methods employable with many variables (foods) is considered. This method was used in trying to find diets allowing for the preferential use of selected foods while respecting recommended dietary allowances, the tastes of the child and other constraints. The theoretical difficulty of transferring this methodology to pediatric dietetics was examined. We solved a simple case utilizing this procedure. PMID- 2223737 TI - Dietary behaviours and sociocultural demographics in Northern Ireland. AB - Subjects aged 16-64 years (592; 258 men and 334 women), randomly selected from the population of Northern Ireland, kept a 7 d weighed record of all food and drink consumed. Social, personal and anthropometric data were also collected. From the weighed records food consumption was described in terms of forty-one food groups. Using principal components analysis, four distinct dietary patterns were generated which were identified as a traditional diet, a cosmopolitan diet, a convenience diet and a 'meat and two veg' diet. These dietary patterns were then correlated with sociocultural, lifestyle and anthropometric variables. It is clear that dietary behaviour is influenced by a number of inter-related sociocultural demographics and that identifiable population groups in Northern Ireland have different dietary behaviours. PMID- 2223738 TI - Haematological studies on pre-menopausal Indian and Caucasian vegetarians compared with Caucasian omnivores. AB - Full blood counts, serum ferritin, vitamin B12 and folate, erythrocyte folate concentrations and nutrient intakes were estimated in twenty-three Indian vegetarian, twenty-two Caucasian omnivores and eighteen Caucasian vegetarian women aged 25-40 years. Energy and copper intakes were lower in the Indian women than in the Caucasians. Intakes of dietary fibre, vitamin C and folate were greater and the proportion of energy derived from fat was lower in the vegetarians than in the omnivores. Vitamin B12 and protein intakes were lower in both vegetarian groups than in the omnivores. Fe intake was similar in all the groups but haem Fe provided one-quarter of the Fe intake of the omnivores. Haemoglobin concentrations were generally inside the normal range in all groups, but were lower in the Indians as were mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH). Higher MCV, MCH and lower erythrocyte (RBC) counts were observed in Caucasian vegetarians compared with the Caucasian omnivores. In both groups of vegetarians, concentrations of serum vitamin B12 and ferritin were markedly lower than in the omnivores. RBC folate concentrations were lower in the Indians than in either of the Caucasian groups when subjects taking supplements were excluded. It is concluded that vegetarians need to ensure they have adequate intakes of Fe and vitamin B12. PMID- 2223739 TI - The effect of methylxanthines on milk volume and composition, and growth of rat pups. AB - A study was conducted to investigate the effect of differential dose levels of methylxanthines on lactational performance, with respect to milk volume and composition and pup growth. The methylxanthines; caffeine, theophylline and theobromine, were administered via drinking water in the proportions occurring in tea, at a dose of 50, 1 and 2 mg/kg body-weight respectively to Wistar albino rats throughout pregnancy and for up to the 14th day of lactation. A fourth group received a mixture of all three methylxanthines. Maternal food and fluid intake and weight changes, as well as weight gain in the litter were monitored thrice weekly. Milk samples were collected from the dams on days 7 and 14 of lactation, while milk volume was measured on days 12-13 by a method using tritiated water. Results showed that caffeine and theobromine significantly enhanced litter weight (P less than 0.01 and 0.05 respectively). In the caffeine group, enhanced litter growth was due to a significant increase (P less than 0.05) in milk volume, consequent to increased maternal food intake (P less than 0.05). In the theobromine group there was only a weak association between increased litter weight and milk volume. Theophylline had no effect on the volume or composition of milk, or litter weight. The combination of all three methylxanthines also failed to produce any of the positive effects observed with separate drug treatments. PMID- 2223740 TI - Effect of vitamin A supplementation on haemoglobin and vitamin A levels during pregnancy. AB - About 450 pregnant women from a low-income group were recruited to study the effect of vitamin A supplementation on plasma vitamin A levels in the mother and cord and on the birth weights of the neonates. Results showed that supplementation with 1800 micrograms vitamin A/d for more than 12 weeks prevented the decline in plasma vitamin A that otherwise occurs during the last few weeks of pregnancy. This improvement in maternal values for vitamin A at a critical time of development favourably affected availability to the fetus, as reflected by the marked elevation in cord levels. Supplementation for a period of 12 weeks was found to be sufficient, since subsequent discontinuation did not alter the beneficial response. Apart from increasing maternal and cord vitamin A levels, vitamin A supplementation along with iron prevented, in this study, the significant decline in haemoglobin occurring at 26-28 weeks of gestation. The birth weights were not altered by vitamin A supplementation. PMID- 2223741 TI - The effect of the level of dietary protein, carbohydrate and fat on urea kinetics in young children during rapid catch-up weight gain. AB - The kinetics of urea metabolism were measured in children recovering from severe malnutrition. For a period of up to 10 d they received one of four diets which provided 711 kJ (170 kcal)/kg per d. Two groups received a diet with a high protein:energy (P:E) ratio of 10-6% (HP), enriched with either fat (HP/F) or maize starch and sucrose (HP/C). Two groups received a diet with a low P:E ratio of 8.8% (LP), enriched with either fat (LP/F) or maize starch and sucrose (LP/C). The rate of weight gain on the HP diets was significantly greater than on the LP diets. There was no difference in urea production between any of the four diets: HP/F 1.23 (SE 0.12), HP/C 1.37 (SE 0.14), LP/F 1.64 (SE 0.22), LP/C 1.15 (SE 0.15) mmol nitrogen/kg per h. On the HP diets urea excretion was 0.77 (SE 0.07) mmol N/kg per h, 61% of production. There was significantly less urea excreted in the urine on diet LP/C than on LP/F (0.36 (SE 0.05) and 0.64 (SE 0.04) mmol N/kg per h respectively). A significantly greater percentage of the urea production was hydrolysed on the LP diets (61%) compared with the HP diets (39%), with the consequence that 50% of urea-N produced was available for synthetic activity on the LP diets compared with 30% on the HP diets. The increase in the urea hydrolysed on the LP diets was equivalent in magnitude to the decreased intake of N, so that overall intake plus hydrolysis did not differ between the LP and the HP diets. Crude N balance was similar on diets HP/F, HP/C and LP/C, but was significantly reduced on diet LP/F. These results show that there is an accommodation in urea kinetics during rapid catch-up weight gain, which becomes evident when the P:E ratio of the diet falls to 8.8%. It is proposed that, for a P:E ratio of 8.8%, protein is limiting for catch-up growth. When the intake has a P:E ratio of 8.8% the pattern of urea kinetics can be modified by the relative proportions of fat and carbohydrate in the diet. The measurement of urea kinetics provides a useful approach to the definition of the adequacy of the protein in the diet. PMID- 2223742 TI - The effect of dietary nitrate on nitrate and nitrite excretion in man. AB - Dietary nitrate and nitrite may affect colonic pathophysiology. These anions influence fermentation, and nitrite has been shown to augment sodium absorption by the colon and participate in the formation of N-nitroso compounds. There is, however, no general agreement as to how much dietary nitrate and nitrite reaches the colon. To help resolve this question, balance studies were performed on six healthy ileostomy subjects who were given diets that varied in nitrate content from 0.83 to 5.20 mmol/d. Nitrate and nitrite excretion in ileal effluent and urine were measured by anion-exchange chromatography with conductivity detection. There was no significant nitrite in the diets, urine or ileal effluent. Dietary nitrate was largely excreted in urine (1.31-4.25 mmol/d). The urinary excretion findings indicated net synthesis of nitrate at low dietary intakes and net catabolism of nitrate at high intakes. Nitrate losses in ileal effluent were very low (0.03-0.05 mmol/d, 0.03-0.06 mmol/kg) and unrelated to intake for all the diets. It is concluded that dietary nitrate and nitrite do not enter the colon from the small intestine in amounts that would affect fermentation and mucosal metabolism in man. The possibility of significant amounts of nitrate reaching the colon via blood in normal subjects has not been excluded. PMID- 2223743 TI - Tissue and whole-body oxygen uptake in fed and fasted steers. AB - The effect of feeding v. fasting, on tissue blood flow, oxygen uptake and proportional contributions of the portal drained viscera (PDV), liver (Expts 1 and 2) and hindquarters (HQ; Expt 2) to whole-body O2 uptake were studied in beef steers. The combined techniques of indirect calorimetry and net tissue flux, the latter being the product of arterio-venous concentration difference and blood flow, were used in the experiments. In response to fasting, whole-body O2 consumption decreased as did O2 uptake by all measured tissues except the liver (trend only in Expt 1). Blood flow to all measured tissues decreased during fasting and fractional uptake of O2 decreased in PDV and increased in liver and HQ (Expt 2). Proportional contribution of specific tissues to whole-body O2 uptake changed when animals were switched from the fed to the fasted state. The percentage consumed by PDV decreased from 25.4 to 19.9, by liver increased from 20.5 to 26.4 and by HQ was unchanged (9.6 and 10.5) in Expt 2. These significant responses in Expt 2 were observed as trends in Expt 1. The changes in proportional contribution of tissues to whole-animal O2 uptake reflect the changing metabolic role of specific tissues to lack of food supply. These findings emphasize the central role of the liver in metabolism and indicate that fasting (catabolic) measurements may not reflect the previous fed (anabolic) physiological state. PMID- 2223744 TI - The effects of underfeeding for 7 d on the thermogenic and physiological response to glucose and insulin infusion (hyperinsulinaemic euglycaemic clamp). AB - The effect of underfeeding for 7 d (at 60 kJ/kg ideal body-weight) on the thermic and physiological responses to glucose and insulin infusions (hyperinsulinaemic euglycaemic clamp) was studied in six healthy women. Underfeeding had no significant effect on baseline metabolic rate, heart rate, forearm blood flow, diastolic blood pressure, blood intermediary metabolites, plasma insulin or catecholamines, but reduced both respiratory exchange ratio (RER; control (C) 0.86 (SE 0.02), underfed (U) 0.75 (SE 0.01); P less than 0.01) and systolic blood pressure (by approximately 10 mmHg, P less than 0.01). Baseline forearm glucose uptake and oxygen consumption were similar in both states. During the final 30 min of the glucose and insulin infusion, metabolic rate rose by 0.43 (SE 0.05) kJ/min in the C state, but no rise was seen in the U state (P less than 0.01). Glucose disposal rate (C 47.9 (SE 1.8), U 47.3 (SE 4.1) mumol/kg per min) and storage rate (C 27.5 (SE 2.4), U 31.6 (SE 3.6) mumol/kg per min) were similar in both states, but glucose oxidation rate was reduced in the U state (C 20.5 (SE 1.7), U 15.4 (SE 0.7) mumol/kg per min; P less than 0.05). RER rose to a higher value in the C state than in the U state (C 0.97 (SE 0.2), U 0.80 (SE 0.01); P less than 0.01). During hyperinsulinaemia, the forearm glucose uptake and O2 consumption rose in both states. No significant differences were seen in the cardiovascular responses to hyperinsulinaemia in either state. Thus underfeeding abolishes the rise in thermogenesis and reduces glucose oxidation during glucose and insulin infusions in healthy women, but does not affect the glucose disposal or storage rates or the other measured responses. PMID- 2223746 TI - Glucose partitioning in the pregnant ewe: effects of undernutrition and exercise. AB - Maternal whole-body glucose entry rate and uterine and umbilical net uptakes of glucose and oxygen were measured in single-pregnant ewes which were either well fed throughout, or fed at 0.3-0.4 predicted energy requirement for 7-21 d during late pregnancy. All ewes were studied while standing at rest and then while walking on a treadmill at 0.7 m/s on a 10 degrees slope for 60 min. Underfed ewes suffered significant decreases in live weight and had lower fetal, but not placental, weights at 140-144 d gestation. Undernutrition also caused large decreases in maternal glycaemia and glucose entry rate, which were associated with equally large decreases in uterine and umbilical net uptakes and O2 quotients of glucose, and with a decrease in placental glucose transfer capacity. Exercise caused increases in maternal blood concentration, entry rate and uterine net uptake of glucose, the magnitudes of which were not significantly affected by plane of nutrition. Umbilical glucose uptake and placental glucose transfer capacity increased during exercise in underfed but not fed ewes. The fractional distribution of maternal glucose to the pregnant uterus, and of uterine glucose uptake to the fetus, were unaltered by undernutrition; during exercise, a disproportionately small fraction of the increased maternal glucose supply went to the uterus. The results confirm that the ovine conceptus responds to nutritional reduction in maternal glucose availability in a manner similar to non uterine maternal tissues. Major reductions in glucose supply appear to override putative glucose-sparing mechanisms which may operate to favour the conceptus in better-nourished animals. PMID- 2223745 TI - Level of nutrition and visceral organ size and metabolic activity in sheep. AB - Thirty-two crossbred wether lambs (initial live-weight 31 kg) were fed on a diet (metabolizable energy (ME) 12.8 MJ/kg) ad lib. (ADLIB) or restricted to maintain body-weight (MAINT) for a 21 d period. On days 0, 7, 14 and 21, four lambs per treatment were slaughtered, visceral organs weighed and tissues sampled. During the 21 d period, ME intake in ADLIB lambs increased quadratically with an average rate of live-weight gain of 425 g/d. In MAINT lambs, live weight (30 kg) was maintained, and daily ME intake (kJ/kg empty body-weight (EBW)0.75) declined (P less than 0.01) quadratically with time. Weights of liver, stomach and small intestines as a percentage of EBW were increased in ADLIB lambs and decreased by 10-33% in MAINT lambs (treatment x day, P less than 0.01). In vitro liver oxygen consumption was not affected by level of feed intake. Estimates of whole-liver O2 consumption (mmol O2/d per kg EBW) increased in ADLIB lambs and were relatively constant in MAINT lambs. These findings suggest that level of feed intake changes the relative proportion of visceral organs to body mass. In addition, the effect of level of feed intake on changes in the relative contribution of visceral organs to whole-body metabolic rate appears to be primarily a result of differences in organ size rather than tissue-specific metabolic activity. PMID- 2223747 TI - Effects of maternal undernutrition and exercise on glucose kinetics in fetal sheep. AB - Fetal glucose kinetics were measured using a combination of isotope-dilution and Fick-principle methodology in single-pregnant ewes which were either well-fed throughout, or fed at 0.3-0.4 predicted energy requirement for 7-21 d during late pregnancy. All ewes were studied while standing at rest and then while walking on a treadmill at 0.7 m/s on a 10 degree slope for 60 min. Underfed ewes suffered major decreases in fetal total disposal rate, fetal-placental transfer and umbilical net uptake of glucose, each of which were significantly related to declines in maternal and fetal blood glucose concentrations respectively. In well fed ewes, fetal endogenous glucose production was negligible, as indicated by the similarity between fetal utilization rate (total glucose disposal rate minus placental uptake of fetal glucose) and umbilical net uptake of glucose, and by nearly identical fetal and maternal arterial blood specific radioactivities of maternally infused D-[2-3H]glucose. By contrast, in underfed ewes, fetal utilization rate greatly exceeded umbilical net uptake of glucose, and the fetal:maternal [3H]glucose specific activity ratio declined significantly, suggesting induction of a substantial rate of fetal endogenous glucogenesis. Exercise caused increases in fetal total glucose disposal rate and glycaemia in fed and underfed ewes. In underfed ewes only, this was accompanied by increased placental uptake of fetal glucose and umbilical net glucose uptake, unchanged fetal glucose utilization and decreased fetal endogenous glucose production. It is concluded that fetal gluconeogenesis makes a major contribution to fetal glucose requirements in undernourished ewes. Increased maternal supply of fetal glucose during exercise substitutes for rather than adds to fetal endogenous glucogenesis. PMID- 2223748 TI - Dietary animal proteins and cholesterol metabolism in rabbits. AB - The effect in rabbits of giving isonitrogenous purified diets containing casein, ovalbumin, fish protein, milk-whey protein and soya-bean protein were compared. The diets were balanced for cholesterol and for the amount and type of fat. When incorporated into low-cholesterol diets (0.08 g cholesterol/kg), casein, ovalbumin and soya-bean protein produced similar levels of serum cholesterol. With a high background of dietary cholesterol (1.5 g/kg), serum cholesterol concentrations increased with soya-bean protein, whey protein, casein and fish protein, in that order. Thus, the hypercholesterolaemic effect of casein in carefully balanced diets was only seen against a high-cholesterol background. The development of hypercholesterolaemia produced by giving fish protein was different from that produced by casein. First, less cholesterol accumulated in the very-low-density-lipoprotein fractions and more in the lipoproteins of higher density with fish protein than with casein. Second, fish protein, unlike casein, did not increase liver cholesterol. Third, transfer of rabbits from a diet containing soya-bean protein to one containing casein resulted in an immediate marked depression in neutral steroid and bile acid excretion in faeces. However, when rabbits were fed on the diet with fish protein after the diet with soya-bean protein, there was no significant depression in neutral steroid output and the depression in bile acid output was delayed. The present study suggests that different animal proteins cause hypercholesterolaemia by different mechanisms. PMID- 2223749 TI - Lipid absorption and intestinal tumour incidence in rats fed on varying levels of calcium and butterfat. AB - The purpose of the 2 x 2 factorial study was to determine the effect of varying levels of dietary calcium (2.5 and 10 g/kg) and butterfat (50 and 200 g/kg) on lipid utilization and on development of colon tumours in animals initiated with 1,2-dimethylhydrazine dihydrochloride. Among rats fed on 200 g butterfat/kg, the fourfold increase in Ca intake induced more than a sevenfold increase in faecal excretion of total lipids and almost a fortyfold increase in faecal excretion of acid-extractable lipid. Among rats fed on 50 g butterfat/kg, the ingestion of supplemental Ca had a less dramatic effect and induced only a twofold increase in faecal excretion of total lipids and a threefold increase in acid-extractable lipid. The volume of intestinal adenocarcinomas was correlated with the excretion of acid-extractable lipid in faeces (R 0.369, P less than 0.02). Caecal enzymic activity was not correlated with tumour incidence or size or faecal lipid excretion. Overall, the fourfold increase in Ca intakes decreased total lipid absorption significantly but by less than 6%. PMID- 2223750 TI - Iron absorption from typical West African meals containing contaminating Fe. AB - Iron absorption from three typical West African meals was measured in fourteen subjects using the extrinsic-tag technique with 59Fe and 55Fe. All meals consisted of maize as the staple food. Meals were prepared in Benin under realistic conditions from locally grown foods. Of the non-haem-Fe in the meals 39 73% did not exchange with the added inorganic radio-Fe tracer, depending on the degree of Fe contamination of meals. Non-haem-Fe absorption was low in each maize meal, but was even lower for those eaten with a vegetable sauce than for those eaten with a fish sauce. When haem-Fe absorption was included, 70.0-160 micrograms Fe was absorbed. Expressed on an energy basis, the bioavailable nutrient density was 3.2-7.0 micrograms/100 kJ (13.4-29.5 micrograms/100 kcal). These findings suggest that total Fe available in the typical diets of West African countries does not meet the physiological requirements of large proportions of the population. PMID- 2223751 TI - Effect of caffeine on zinc absorption and Zn concentration in rat tissue. AB - The purposes of the present study were to determine whether caffeine has an effect on zinc absorption and tissue levels of Zn. Under anaesthesia, one side of the intestine of female rats was connected to infusion pumps and an infused solution (first caffeine and later Zn solution) was collected from the other side of the intestine using either 300 mm or the whole small intestine to determine Zn absorption. In a further study, different doses of caffeine solution were injected directly into the femoral vein and a saline or Zn solution was infused into the intestine to measure Zn absorption and tissue Zn concentrations. The results consistently showed that the caffeine solution infused into the intestine did not affect intestinal Zn absorption nor was absorption affected by the direct injection of caffeine into the vein. In contrast, injection of different doses of the caffeine solution significantly decreased Zn tissue levels for the heart only. Calcium concentrations in the heart tissue were also decreased, but not magnesium concentrations. Tissue Zn levels recovered immediately on infusion of a Zn solution into the intestine. PMID- 2223752 TI - Large bowel fermentation in rats given diets containing raw peas (Pisum sativum). AB - The digestion of non-starch polysaccharides (NSP) was studied in rats given semi purified diets containing 0-500 g raw peas (Pisum sativum)/kg. NSP were equally well digested at all inclusion levels with digestibilities for individual constituents ranging from 0.58 for xylans to 0.99 for arabinose-containing polymers with a total NSP digestibility of 0.79. Increasing the dietary pea inclusion rate increased the amount of substrate flowing to the large bowel (LB) and this was associated with marked increases in caecal tissue and contents masses, a reduction in caecal transit time from 0.88 to 0.43 d and a threefold increase in faecal bacterial output. Caecal pH fell as did the molar proportions of acetate, isobutyrate, isovalerate and valerate whilst butyrate increased when peas were included in the diet. Possible mechanisms for these fermentation end product changes are discussed. Pea inclusion in the diet was associated with increased volatile fatty acid and 3-hydroxy butyrate concentrations in portal and heart blood. It was concluded that peas are a rich source of fermentable polysaccharides which produce a LB fermentation pattern of potential health benefit. PMID- 2223753 TI - Rhodopsin-stimulated activation-deactivation cycle of transducin: kinetics of the intrinsic fluorescence response of the alpha subunit. AB - The intrinsic tryptophan fluorescence of the alpha subunit of transducin (alpha T) has been shown to be sensitive to the binding of guanine nucleotides, with the fluorescence being enhanced by as much as 2-fold upon the binding of GTP or nonhydrolyzable GTP analogues [cf. Phillips and Cerione (1988) J. Biol. Chem. 263, 15498-15505]. In this work, we have used these fluorescence changes to analyze the kinetics for the activation (GTP binding)-deactivation (GTPase) cycle of transducin in a well-defined reconstituted phospholipid vesicle system containing purified rhodopsin and the alpha T and beta gamma T subunits of the retinal GTP-binding protein. Both the rate and the extent of the GTP-induced fluorescence enhancement are dependent on [rhodopsin], while only the rate (and not the extent) of the GTP gamma S-induced enhancement is dependent on the levels of rhodopsin. Comparisons of the fluorescence enhancements elicited by GTP gamma S and GTP indicate that the GTP gamma S-induced enhancements directly reflect the GTP gamma S-binding event while the GTP-induced enhancements represent a composite of the GTP-binding and GTP hydrolysis events. At high [rhodopsin], the rates for GTP binding and GTPase are sufficiently different such that the GTP induced enhancement essentially reflects GTP binding. A fluorescence decay, which always follows the GTP-induced enhancement, directly reflects the GTP hydrolytic event. The rate of the fluorescence decay matches the rate of [32P]Pi production due to [gamma-32P]GTP hydrolysis, and the decay is immediately reversed by rechallenging with GTP. The GTP-induced fluorescence changes (i.e., the enhancement and ensuing decay) could be fit to a simple model describing the activation-deactivation cycle of transducin. The results of this modeling suggest the following points: (1) the dependency of the activation-deactivation cycle on [rhodopsin] can be described by a simple dose response profile; (2) the rate of the rhodopsin-stimulated activation of multiple alpha T(GDP) molecules is dependent on [rhodopsin] and when [alpha T] greater than [rhodopsin], the activation of the total alpha T pool may be limited by the rate of dissociation of rhodopsin from the activated alpha T(GTP) species; and (3) under conditions of optimal rhodopsin-alpha T coupling (i.e., high [rhodopsin]), the cycle is limited by GTP hydrolysis with the rate of Pi release, or any ensuing conformational change, being at least as fast as the hydrolytic event. PMID- 2223755 TI - Pairwise specificity and sequential binding in enzyme catalysis: thymidylate synthase. AB - The structures of thymidylate synthase (TS) from Escherichia coli, in ternary complexes with substrate and an analogue of the cofactor, are the basis of a stereochemical model for a key reaction intermediate in the catalyzed reaction. This model is used to compare the reaction chemistry and chirality of the transferred methyl group with structures of the components, to identify those residues that participate, and to propose a stereochemical mechanism for catalysis by TS. Effects of chemical modification of specific amino acid residues and site-directed mutations of residues are correlated with structure and effects on enzyme mechanism. The ordered binding sequence of substrate deoxyuridine monophosphate and methylenetetrahydrofolate can be understood from the structure, where each forms a large part of the binding site for the other. The catalytic site serves to orient the reactants, which are sequestered along with many water molecules within a cavernous active center. Conformational changes during the reaction could involve nearby residues in ways that are not obvious in this complex. PMID- 2223754 TI - Structure, multiple site binding, and segmental accommodation in thymidylate synthase on binding dUMP and an anti-folate. AB - The structure of Escherichia coli thymidylate synthase (TS) complexed with the substrate dUMP and an analogue of the cofactor methylenetetrahydrofolate was solved by multiple isomorphous replacement and refined at 1.97-A resolution to a residual of 18% for all data (16% for data greater than 2 sigma) for a highly constrained structure. All residues in the structure are clearly resolved and give a very high confidence in total correctness of the structure. The ternary complex directly suggests how methylation of dUMP takes place. C-6 of dUMP is covalently bound to gamma S of Cys-198(146) during catalysis, and the reactants are surrounded by specific hydrogen bonds and hydrophobic interactions from conserved residues. Comparison with the independently solved structure of unliganded TS reveals a large conformation change in the enzyme, which closes down to sequester the reactants and several highly ordered water molecules within a cavernous active center, away from bulk solvent. A second binding site for the quinazoline ring of the cofactor analogue was discovered by withholding addition of reducing agent during crystal storage. The chemical change in the protein is slight, and from difference density maps modification of sulfhydryls is not directly responsible for blockade of the primary site. The site, only partially overlapping with the primary site, is also surrounded by conserved residues and thus may play a functional role. The ligand-induced conformational change is not a domain shift but involves the segmental accommodation of several helices, beta strands, and loops that move as units against the beta-sheet interface between monomers. PMID- 2223756 TI - Folding and stability of trp aporepressor from Escherichia coli. AB - Equilibrium and kinetic studies of the urea-induced unfolding of trp aporepressor from Escherichia coli were performed to probe the folding mechanism of this intertwined, dimeric protein. The equilibrium unfolding transitions at pH 7.6 and 25 degrees C monitored by difference absorbance, fluorescence, and circular dichroism spectroscopy are coincident within experimental error. All three transitions are well described by a two-state model involving the native dimer and the unfolded monomer; the free energy of folding in the absence of denaturant and under standard-state conditions is estimated to be 23.3 +/- 0.9 kcal/mol of dimer. The midpoint of the equilibrium unfolding transition increases with increasing protein concentration in the manner expected from the law of mass action for the two-state model. We find no evidence for stable folding intermediates. Kinetic studies reveal that unfolding is governed by a single first-order reaction whose relaxation time decreases exponentially with increasing urea concentration and also decreases with increasing protein concentration in the transition zone. Refolding involves at least three phases that depend on both the protein concentration and the final urea concentration in a complex manner. The relaxation time of the slowest of these refolding phases is identical with that for the single phase in unfolding in the transition zone, consistent with the results expected for a reaction that is kinetically reversible. The two faster refolding phases are presumed to arise from slow isomerization reactions in the unfolded form and reflect parallel folding channels. PMID- 2223757 TI - Structure and function of hemoglobin variants at an internal hydrophobic site: consequences of mutations at the beta 27 (B9) position. AB - We have studied the structure-function relationships in newly discovered hemoglobin (Hb) mutants with substitutions occurring at the tight and highly hydrophobic cluster between the B and G helices in the beta chains, namely, Hb Knossos or beta A27S and Hb Grange-Blanche or beta A27V. The beta A27S mutant has a 50% decrease in oxygen affinity relative to native human Hb A, while the beta A27V mutant has an increased oxygen affinity. We have also engineered the artificial beta A27T mutation through site-directed mutagenesis. This new mutant exhibits functional properties similar to those of Hb A. None of these mutants is unstable. X-ray analyses show that the substitution of Val for Ala may reduce the relative stability of the T structure of the molecule through packing effects in the beta chains; for the beta A27S mutant a new hydrogen bond between serine and the carbonyl O at beta 23 (B5) Val is observed and is likely to increase the relative stability of the T structure in the mutant hemoglobin. However, no significant changes in the crystals were observed for these mutants between the quaternary R and T structures relative to native Hb A. We conclude that small tertiary structural changes in the tight hydrophobic B-G helix interface are sufficient to induce functional abnormalities resulting in either low or high intrinsic oxygen affinities. PMID- 2223758 TI - Mechanistic studies of ionizing radiation and oxidative mutagenesis: genetic effects of a single 8-hydroxyguanine (7-hydro-8-oxoguanine) residue inserted at a unique site in a viral genome. AB - T4 RNA ligase was used to construct a deoxypentanucleotide containing a single 8 hydroxyguanine (7-hydro-8-oxoguanine; G8-OH) residue, which is one of the putatively mutagenic DNA adducts produced by oxidants and ionizing radiation. The pentamer d(GCTAG8-OH)p was prepared by the ligation of a chemically synthesized acceptor molecule, d(GCTA), to an adducted donor, 8-hydroxy-2'-deoxyguanosine 5',3'-bisphosphate. The acceptor was efficiently converted to the reaction product (greater than 95%), and the final product yield was 50%. Following 3' dephosphorylation, the pentamer was characterized by UV spectroscopy, by high pressure liquid chromatography, and by gas chromatography-mass spectrometry of the nucleosides released by enzymatic hydrolysis. Both d(GCTAG8-OH) and an unmodified control were 5'-phosphorylated by using [gamma -32P]ATP and incorporated covalently by DNA ligase into a five-base gap at a unique NheI restriction site in the otherwise duplex genome of an M13mp19 derivative. The ligation product contained G8-OH at the 3' residue of an in-frame amber codon (5' TAG-3') (genome position 6276) of the phage lacZ alpha gene. The adduct was part of a nonsense codon in a unique restriction site in order to facilitate the identification and selection of mutants generated by the replication of the modified genome in Escherichia coli. Both control and adducted pentamers ligated into the genome at 50% of the maximum theoretical efficiency, and nearly all (approximately 90%) of the site-specifically adducted products possessed pentanucleotides that were covalently linked at both 5' and 3' termini. The G8-OH lesion in the NheI site inhibited the cleavage of the site by a 200-fold excess of NheI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223759 TI - Differential scanning calorimetry study of mixed-chain phosphatidylcholines with a common molecular weight identical with diheptadecanoylphosphatidylcholine. AB - To examine the thermotropic phase behavior of various mixed-chain phosphatidylcholines in excess water and to compare it with the known behavior of identical-chain phosphatidylcholines, we have carried out high-resolution differential scanning calorimetric (DSC) studies on aqueous dispersions of 10 different mixed-chain phosphatidylcholines. These lipids, C(16):C(18)PC, C(18):C(16)PC, C(15):C(19)PC, C(19):C(15)PC, C(14):C(20)PC, C(20):C(14)PC, C(13):C(21)PC, C(21):C(13)PC, C(12):C(22)PC, and C(22):C(12)PC, have a common molecular weight which is the same as that of C(17):C(17)PC, an identical-chain phosphatidylcholine with a molecular weight of 762.2. When the values of any of the thermodynamic parameters (Tm, delta H, and delta S) of the mixed-chain phosphatidylcholines and C(17):C(17)PC are plotted against the normalized chain length difference (delta C/CL), a linear function with negative slope is obtained provided that the value of delta C/CL is within the range of 0.09-0.4. The linear relationship suggests that these mixed-chain phospholipids are packed in the gel state bilayer similar to the bilayer structure of C(17):C(17)PC at T less than Tm; however, the negative slope suggests that the conformational statistics of the hydrocarbon chain and the lateral lipid-lipid interactions of these phosphatidylcholines in the gel-state bilayer are perturbed proportionally by a progressive increase in the chain-length inequivalence between the two acyl chains within each lipid molecule. When the value of delta C/CL for mixed-chain phosphatidylcholines reaches the range of 0.44-0.55, the thermotropic phase behavior deviates markedly from that of less asymmetric phosphatidylcholines, suggesting that these highly asymmetric lipids are packed into mixed interdigitated bilayers at T less than Tm. The heating and cooling pathways of aqueous dispersions prepared from the 10 mixed-chain phospholipids are also discussed. PMID- 2223760 TI - Differential scanning calorimetric study of a homologous series of fully hydrated saturated mixed-chain C(X):C(X + 6) phosphatidylcholines. AB - The successive high-resolution differential scanning calorimetric (DSC) thermograms for aqueous dispersions of a homologous series of mixed-chain phosphatidylcholines, C(X):C(X + 6)PC, have been recorded and analyzed. In this series of saturated mixed-chain phosphatidylcholines, the total number of carbon atoms in the sn-1 acyl chain increases from 11 to 20, and the sn-2 acyl chain is always 6 methylene units longer than the sn-1 acyl chain. In the initial heating DSC thermograms, two prominent endothermic transitions are detected for all the samples prepared from the various C(X):C(X + 6)PCs except C(12):C(18)PC. In contrast, a single exothermic transition is observed on cooling for all the samples except C(13):C(19)PC. The temperature difference between the two endothermic transitions increases linearly as the acyl chain length of C(X):C(X + 6)PC becomes progressively longer. Interestingly, the main phase transition occurs before the subtransition for C(11):C(17)PC dispersions. Our DSC data further demonstrate that the thermodynamic parameters (Tm, delta H, and delta S) associated with the main phase transition for fully hydrated C(13):C(19)PC and other identical MW phosphatidylcholines are inversely related to the corresponding values of the chain-length inequivalence (delta C/CL) for these lipids. This linear relationship can be employed to map the Tm values for aqueous dispersions prepared from a large number of mixed-chain phosphatidylcholines whose values of delta C/CL are within the range of 0.1-0.4. PMID- 2223761 TI - Ca2+, Mg2+, Li+, Na+, and K+ distributions in the headgroup region of binary membranes of phosphatidylcholine and phosphatidylserine as seen by deuterium NMR. AB - The binding of calcium, magnesium, lithium, potassium, and sodium to membrane bilayers of 5 to 1 (M/M) 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and 1 palmitoyl- 2-oleoylphosphatidylserine (POPS) was investigated by using deuterium nuclear magnetic resonance (2H NMR). Both lipids were deuteriated on their polar headgroups, and spectra were obtained at 25 degrees C in the liquid-crystalline phase as a function of salt concentration. The spectra obtained with calcium were correlated with 45CaCl2 binding studies to determine the effective membrane-bound calcium at low calcium binding, up to 0.78 calcium per POPS. Deuterium quadrupolar splittings of both POPC and POPS headgroups were shown to be very sensitive to calcium binding. The behavior of these two headgroups over a wide range of CaCl2 concentrations suggests that Ca2+ binding occurs in at least two steps, the first step being achieved with 0.5 M CaCl2, with a stoichiometry of 0.5 Ca2+ per POPS. Correlations of the deuterium Ca2+ binding data with related data obtained after incorporation of a cationic integral peptide showed that the effects of these two cationic molecules of the POPS headgroup are qualitatively similar, and provided further support for two-step Ca2+ binding to the POPC/POPS 5:1 membranes. The corresponding data obtained with magnesium, lithium, and potassium indicate that these cations interact with both the choline and serine headgroups. The amplitudes of headgroup perturbations could be partly correlated to the relative affinities of the metallic cations for the lipid membrane. The two-step binding described with Ca2+ appears to be relevant to the Mg2+ data, and in certain limits to the Li+ data. The data were interpreted in terms of conformational changes of the lipid headgroups induced by an electric field due to the charges of the membrane-bound metallic cations. A conformational change of the serine headgroup induced by the membrane-bound charges is proposed. We propose that the metallic cations can be differentiated on the basis of their respective spatial distribution functions relative to the choline and serine headgroups. According to this interpretation, the divalent cations Ca2+ and Mg2+ are more deeply buried in the membrane than monovalent Na+ and K+, the case of Li+ being intermediate of the latter two. This conclusion is discussed in relation to fundamental theories of the spatial distribution of ions near the interface between water and smooth charged solid surfaces. PMID- 2223762 TI - Isolation and characterization of a novel eukaryotic monofunctional NAD(+) dependent 5,10-methylenetetrahydrofolate dehydrogenase. AB - An NAD(+)-dependent 5,10-methylenetetrahydrofolate (THF) dehydrogenase has been purified to homogeneity from the yeast Saccharomyces cerevisiae. The purified enzyme exhibits a final specific activity of 5.4 units mg-1 and is represented by a single protein of apparent Mr = 33,000-38,000 as determined by sodium dodecyl sulfate gel electrophoresis. A native Mr = 64,000 was determined by gel filtration, suggesting a homodimer subunit structure. Cross-linking experiments with dimethyl suberimidate confirmed the dimeric structure. The enzyme is specific for NAD+ and is not dependent on Mg2+ for activity. The forward reaction initial velocity kinetics are consistent with a sequential reaction mechanism. With this model, Km values for NAD+ and (6R,S)-5,10-methylene-THF are 1.6 and 0.06 mM, respectively. In contrast to all other previously described eukaryotic 5,10-methylene-THF dehydrogenases, the purified enzyme is apparently monofunctional, with undetectable 5,10-methenyl-THF cyclohydrolase and 10-formyl THF synthetase activities. Subcellular fractionation of yeast indicates the enzyme is cytoplasmic, with no NAD(+)-dependent 5,10-methylene-THF dehydrogenase detectable in mitochondria. The activity was found in all yeast strains examined, at all stages of growth from the lag phase through the stationary phase. PMID- 2223763 TI - Design and characterization of hirulogs: a novel class of bivalent peptide inhibitors of thrombin. AB - A novel class of synthetic peptides has been designed that inhibit the thrombin catalytic site and exhibit specificity for the anion-binding exosite (ABE) of alpha-thrombin. These peptides, called "hirulogs", consist of (i) an active-site specificity sequence with a restricted Arg-Pro scissile bond, (ii) a polymeric linker of glycyl residues from 6 to 18 A in length, and (iii) an ABE recognition sequence such as that in the hirudin C-terminus. Hirulog-1 ([D-Phe)-Pro-Arg-Pro (Gly)4-Asn-Gly-Asp-Phe-Glu-Glu-Ile- Pro-Glu-Tyr-Leu] inhibits the thrombin catalyzed hydrolysis of a tripeptide p-nitroanilide substrate with Ki = 2.3 nM. In contrast, the synthetic C-terminal hirudin peptide S-Hir53-64, which binds to the thrombin ABE, blocked the fibrinogen clotting activity of the enzyme with Ki = 144 nM but failed to inhibit the hydrolysis of p-nitroanilide substrates at concentrations as high as 1 mM. In addition, the pentapeptide (D-Phe)-Pro-Arg-Pro Gly, which comprises the catalytic-site inhibitor moiety of hirulog-1, was determined to have a Ki for thrombin inhibition greater than 2 microM. Hirulog-1, but not S-Hir53-64, was found to inhibit the incorporation of [14C]diisopropyl fluorophosphate in thrombin. Hirulog-1 appears specific for thrombin as it lacks inhibitory activities toward human factor Xa, human plasmin, and bovine trypsin at inhibitor:enzyme concentrations 3 orders of magnitude higher than those required to inhibit thrombin. The optimal inhibitory activity of hirulog-1 depends upon all three components of its structure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223765 TI - Affinity labeling of bovine liver glutamate dehydrogenase with 8-[(4-bromo-2,3 dioxobutyl)thio]adenosine 5'-diphosphate and 5'-triphosphate. AB - Bovine liver glutamate dehydrogenase reacts with 8-[(4-bromo-2,3 dioxobutyl)thio]adenosine 5'-diphosphate (8-BDB-TA-5'-DP) and 5'-triphosphate (8 BDB-TA-5'-TP) to yield enzyme with about 1 mol of reagent incorporated/mol of enzyme subunit. The modified enzyme is catalytically active but has decreased sensitivity to inhibition by GTP, reduced extent of activation by ADP, and diminished inhibition by high concentrations of NADH. Since modified enzyme, like native glutamate dehydrogenase, reversibly binds more than 1 mol each of ADP and GTP, it is unlikely that 8-BDB-TA-5'-TP reacts directly within either the ADP or GTP regulatory sites. The rate constant for reaction of enzyme exhibits a nonlinear dependence on reagent concentration with KD = 89 microM for 8-BDB-TA-5' TP and 240 microM for 8-BDB-TA-5'-DP. The ligands ADP and GTP alone and NADH alone produce only small decreases in the rate constant for the reaction of enzyme with 8-BDB-TA-5'-TP, but the combined addition of 5 mM NADH + 200 microM GTP reduces the reaction rate constant more than 10-fold and the reagent incorporation to about 0.1 mol/mol of enzyme subunit. These results suggest that 8-BDB-TA-5'-TP reacts as a nucleotide affinity label in the region of the GTP dependent NADH regulatory site of bovine liver glutamate dehydrogenase. PMID- 2223764 TI - Probing the coenzyme specificity of glyceraldehyde-3-phosphate dehydrogenases by site-directed mutagenesis. AB - By combining our knowledge of the crystal structure of the glycolytic NAD dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the sequence of the photosynthetic NADP-dependent GAPDH of the chloroplast, two particular amino acid residues were predicted as the principal determinants of differing coenzyme specificity. By use of site-directed mutagenesis, the amino acids Leu 187 and Pro 188 of GAPDH from Bacillus stearothermophilus have been replaced with Ala 187 and Ser 188, which occur in the sequence from the chloroplast enzyme. The resulting mutant was shown to be catalytically active not only with its natural coenzyme NAD but also with NADP, thus confirming the initial hypothesis. This approach has not only enabled us to alter the coenzyme specificity by minimal amino acid changes but also revealed factors that control the relative affinity of the enzyme for NAD and NADP. PMID- 2223766 TI - Substrate-dependent shift of optimum pH in porcine pancreatic alpha-amylase catalyzed reactions. AB - Porcine pancreatic alpha-amylase (EC 3.2.1.1, abbreviated as PPA) hydrolyzes alpha-D-(1,4) glucosidic bonds in starch and amylose at random, and the optimum pH for the substrates is 6.9. The optimum pH, however, shifted to 5.2 for the hydrolytic reaction of low molecular weight oligosaccharide substrates such as p nitrophenyl alpha-D-maltoside, gamma-cyclodextrin, maltotetaitol, and maltopentaitol. The optimum pH for the oligosaccharides consisting of more than five glucose residues, such as maltopentaose and maltohexaitol, was 6.9. From the analysis of the hydrolysates, it was clear that the shift of the optimum pH occurred only when the fifth subsite of PPA in the productive binding modes was occupied by a glucosyl residue of the substrates. The value of Km was independent of pH between 4 and 10 but that of kcat was dependent on pH. The pH profiles of kcat for the above substrates did not fit a simple bell-shaped curve predicted by a two-catalytic-group mechanism. Instead, they were well analyzed theoretically by three pK values and two intrinsic kcat values. Enthalpy changes for the three pK's (4.90, 5.35, and 8.55 at 30 degrees C) were determined from the temperature dependence of pH profiles for maltopentaitol and maltohexaitol to be 0.0, 2.87, and 7.33 kcal/mol, respectively. These results indicate that productive binding modes of the substrates directly affect the catalytic function of the enzyme. From the present thermodynamic analysis and reported three dimensional structure at the active site of PPA [Buisson, G. (1987) EMBO J. 6, 3909-3916], one can assume that a histidyl residue (101, 201, or 299) acts as a proton donor and two carboxyl groups (Asp 197, Glu 233, or Asp 300) act as proton donors or acceptors, and the productive binding mode covering the fifth subsite changes configurations between the catalytic residues and the glucosidic bond hydrolyzed and modulates kinetic parameters depending on pH. PMID- 2223767 TI - Changing the insulin receptor to possess insulin-like growth factor I ligand specificity. AB - To examine the role of the N-terminal part of the insulin-like growth factor I (IGF-I) receptor and insulin receptor in determining ligand specificity, we prepared an expression vector encoding a hybrid receptor where exon 1 (encoding the signal peptide and seven amino acids of the alpha-subunit), exon 2, and exon 3 of the insulin receptor were replaced with the corresponding IGF-I receptor cDNA (938 nucleotides). To allow direct quantitative comparison of the binding capabilities of this hybrid receptor with those of the human IGF-I receptor and the insulin receptor, all three receptors were expressed in baby hamster kidney (BHK) cells as soluble molecules and partially purified before characterization. The hybrid IGF-I/insulin receptor bound IGF-I with an affinity comparable to that of the wild-type IGF-I receptor. In contrast, the hybrid receptor no longer displayed high-affinity binding of insulin. These results directly demonstrate that it is possible to change the specificity of the insulin receptor to that of the IGF-I receptor and, furthermore, that the binding specificity for IGF-I is encoded within the nucleotide sequence from 135 to 938 of the IGF-I receptor cDNA. Since the hybrid receptor only bound insulin with low affinity, the insulin binding region is likely to be located within exons 2 and 3 of the insulin receptor. PMID- 2223768 TI - Primary structure of the major pepsin inhibitor from the intestinal parasitic nematode Ascaris suum. AB - The major pepsin inhibitor from Ascaris suum was isolated by affinity chromatography and chromatofocusing. Its amino acid sequence was determined by automated Edman degradation of peptide fragments. Peptides were produced by chemical and enzymatic cleavage of pyridylethylated protein and were purified by reverse-phase high-performance liquid chromatography. The inhibitor consists of 149 residues with the following sequence: QFLFSMSTGP10FICTVKDNQV20FVANLPWTML30EGDDIQVGKE40 FAARVEDCTN50VKHDMAPTCT60KPPPFCGPQD70MKMFNFVGCS80VLGNKLFIDQ90KYVRDLTAK D100 HAEVQTFREK110IAAFEEQQEN120QPPSSGMPHG130AVPAGGLSPP140PPPSFCTVQ149. It has a molecular weight of 16,396. All cysteines are engaged as disulfide bonds: Cys(13) Cys(59), Cys(48)-Cys(66), and Cys(79)-Cys(146). The protein is probably composed of two domains connected by a short hydrophobic region. This is the first aspartyl protease inhibitor of animal origin that has been sequenced. The sequence has no significant homology with any other known protein. PMID- 2223769 TI - The cytochrome P-450cam binding surface as defined by site-directed mutagenesis and electrostatic modeling. AB - Cytochrome P-450cam cationic surface charges at Lys 344, Arg 72, and Lys 392 have been altered by site-directed mutagenesis techniques. The residues at Lys 344 and Arg 72 were previously suggested as salt bridge contacts in the cytochrome b5 cytochrome P-450cam association complex and implicated in the physiological putidaredoxin-cytochrome P-450cam complex [Stayton, P. S., Poulos, T. L., & Sligar, S. G. (1989) Biochemistry 28, 8201-8205]. Mutations to neutralize the basic charge at Arg 72 (R72Q) and to both neutralize and reverse the charge at Lys 344 (K344Q, K344E) resulted in alteration of NADH oxidation rates in the reconstituted physiological electron-transfer system, which is rate limited by putidaredoxin-cytochrome P-450cam electron transfer. The steady-state Vmax values were apparently unperturbed, suggesting that the observed rate differences were largely attributable to Km effects. The Km values observed for the K344Q (24 microM) and K344E (32 microM) mutants are in the direction expected for neutralization and reversal of a salt bridge charge interaction. A control mutation at a basic surface charge located away from the proposed site of interaction, Lys 392 (K392Q), resulted in overall activities quantitated by NADH oxidation rates that are similar to that of wild-type cytochrome P-450cam. Calculation of the cytochrome P-450cam electrostatic field revealed a patch of positive potential at the modeled cytochrome b5 interaction site lying directly above the nearest proximal approach to the buried heme prosthetic group. These results provide experimental and theoretical evidence for the modeled cytochrome P-450cam binding site implicated in both cytochrome b5 and putidaredoxin association.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223771 TI - Proton nuclear magnetic resonance assignments and secondary structure determination of the ColE1 rop (rom) protein. AB - The complete resonance assignment of the ColE1 rop (rom) protein at pH 2.3 was obtained by two-dimensional (2D) proton nuclear magnetic resonance spectroscopy (1H NMR) at 500 and 600 MHz using through-bond and through-space connectivities. Sequential assignments and elements of regular secondary structure were deduced by analysis of nuclear Overhauser enhancement spectroscopy (NOESY) experiments and 3JHN alpha coupling constants. One 7.2-kDa monomer of the homodimer consists of two antiparallel helices connected by a hairpin loop at residue 31. The C terminal peptide consisting of amino acids 59-63 shows no stable conformation. The dimer forms a four-helix bundle with opposite polarization of neighboring elements in agreement with the X-ray structure. PMID- 2223770 TI - Analysis of the backbone dynamics of interleukin-1 beta using two-dimensional inverse detected heteronuclear 15N-1H NMR spectroscopy. AB - The backbone dynamics of uniformly 15N-labeled interleukin-1 beta are investigated by using two-dimensional inverse detected heteronuclear 15N-1H NMR spectroscopy. 15N T1, T2, and NOE data at a spectrometer frequency of 600 MHz are obtained for 90% of the backbone amide groups. The data provide evidence for motions on three time scales. All the residues exhibit very fast motions on a time scale of approximately less than 20-50 ps that can be characterized by a single-order parameter with an average value of 0.82 +/- 0.05. For a model comprising free diffusion within a cone, these residue-specific order parameters translate to an average cone semiangle of 20.7 +/- 3.3 degrees. Thirty-two residues also display motions on a time scale of 0.5-4 ns, slightly less than the overall rotational correlation time of the protein (8.3 ns). These additional motions must be invoked to account for the discrepancy between experiment and the simplest theoretical formulation in which the internal motions are described by only two parameters, a generalized order parameter and an effective correlation time [Lipari, G., & Szabo, A. (1982a) J. Am. Chem. Soc. 104, 4546-4559]. In particular, while the simple formulation can account for the 15N T1 and T2 data, it fails to account for the 15N-1H NOE data and yields calculated values for the NOEs that are either too small or negative, whereas the observed NOEs are positive. With the introduction of two internal motions that are faster than the rotational correlation time and differ in time scales by at least 1-2 orders of magnitude [Clore, G. M., Szabo, A., Bax, A., Kay, L. E., Driscoll, P. C., & Gronenborn, A. M. (1990) J. Am. Chem. Soc. 112, 4989-4991], all the relaxation data for these 32 residues can be fitted by two order parameters and an effective correlation time for the slower of the two internal motions. A simple model for these two motions is one in which the very fast motion involves axially symmetric diffusion within a cone, while the slower motion comprises jumps between two different orientations of the NH vector. For such a model the jump angle (excluding the C-terminal residue) ranges from 15 degrees to 69 degrees with a mean value of 28.6 +/- 14.0 degrees. Another 42 residues are characterized by some sort of motion on the 30-ns-10-ms time scale, which results in 15N line broadening due to chemical exchange between different conformational substates with distinct 15N chemical shifts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2223772 TI - Modification of the adipocyte lipid binding protein by sulfhydryl reagents and analysis of the fatty acid binding domain. AB - The adipocyte lipid binding protein (ALBP) is a member of a multigene family of low molecular weight proteins which stoichiometrically and saturably bind hydrophobic ligands and presumably facilitate intracellular lipid metabolism. To probe the structure-function relationship of the binding domain of ALBP, chemical modification has been employed. Modification of the two cysteinyl residues of ALBP (Cys1 and Cys117) with a variety of sulfhydryl reagents decreased the apparent affinity for oleic acid in the following order of effectiveness: methyl methanethiosulfonate much much less than p-(chloromercuri)benzenesulfonic acid less than N-ethylmaleimide (NEM) = 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). Thiol titration of ALBP with DTNB in the presence of bound oleate resulted in the modification of a single cysteinyl residue. The oleate-protected cysteine was identified as Cys117 by modification with a combination of reversible (DTNB) and irreversible (NEM) sulfhydryl reagents in the presence or absence of saturating oleic acid. Cys117-NEM ALBP exhibited a large decrease in binding affinity while Cys1-NEM ALBP exhibited normal binding properties. Neither the modification of ALBP with NEM nor the addition of oleic acid had a significant effect on protein structure, as judged by circular dichroic analysis. These results suggest that Cys117 of ALBP resides in the ligand binding domain and that site-specific modification can be utilized to assess the conformational flexibility of the binding cavity. PMID- 2223773 TI - Nucleotide sequence and expression of a cDNA encoding chick brain actin depolymerizing factor. AB - Chick brain actin depolymerizing factor (ADF) is a 19-kDa protein that severs actin filaments and binds actin monomers. We have obtained a cDNA encoding ADF by screening a chick embryo lambda gt11 cDNA library with both a rabbit anti-ADF antiserum and two oligonucleotide probes. Several non-full-length clones of 636 bases and one full-length clone of 1886 bases were isolated and sequenced. The full-length cDNA encodes a protein of 165 amino acids with a calculated molecular weight of 18,520. The deduced amino acid sequence shows 73% identity with the porcine brain actin binding protein cofilin. The coding region of the ADF cDNA has been placed in an expression vector, and the resulting protein shows immunoreactivity with an anti-ADF antiserum but not with an anti-cofilin antibody. The expressed ADF has been purified and has an actin depolymerizing activity identical with that of brain ADF. Like cofilin, ADF contains a sequence similar to the nuclear transport signal sequence of the SV40 large T antigen and a calcium/calmodulin-dependent protein kinase II phosphorylation consensus sequence. Northern blots of both embryonic chick brain and muscle RNA revealed two ADF mRNAs of length 2.1 and 0.9 kilobases. Southern blots suggest that the ADF gene is present in a single copy within the chicken genome. ADF contains regions of homology with other actin binding proteins including tropomyosin, gelsolin, and depactin. PMID- 2223774 TI - Sequential assignment of the 1H nuclear magnetic resonance spectrum of barnase. AB - Two-dimensional nuclear magnetic resonance spectroscopy has been used to study the bacterial ribonuclease barnase (MW 12,382). Resonance assignments have been made for protons in all of the 110 residues. Analysis of medium- and long-range contacts in NOESY spectra has demonstrated that the major elements of secondary structure in barnase in solution are essentially identical with those found in the crystal structure. PMID- 2223775 TI - Fluorescence and NMR investigations on the ligand binding properties of adenylate kinases. AB - A new system for measurement of affinities of adenylate kinases (AK) for substrates and inhibitors is presented. This system is based on the use of the fluorescent ligand alpha,omega-di[(3' or 2')-O-(N-methylanthraniloyl)adenosine 5'] pentaphosphate (mAP5Am), which is an analogue of the bisubstrate inhibitor diadenosine pentaphosphate (AP5A). It allows the determination of dissociation constants for any ligand in the range of 1 x 10(-9) to 5 x 10(-2) M. Affinities for different bisubstrate inhibitors (AP4A, AP5A, AP6A) and substrates (AMP, ADP, ATP, GTP) were determined in the presence and absence of magnesium. An analysis of the binding of bisubstrate inhibitors is proposed and applied to these data. The techniques are used to describe the properties of a mutant enzyme with Gln-28 ---His (Q28H) prepared by site-directed mutagenesis in comparison to those of wild-type AK from Escherichia coli. This newly introduced histidine is already present in most other adenylate kinases and was regarded to be important or even essential for the catalytic reaction of AK. Temperature denaturation experiments indicate that the mutant enzyme has the same thermal stability as the wild-type enzyme and, as NMR studies indicate, also a very similar structure. However, steady-state catalytic studies and binding experiments showed that the affinities for substrates and inhibitors are elevated from 3-fold (AMP) to 5-fold (ATP) to 15-fold (AP5A) compared to those of the wild-type enzyme. Together with the results obtained by Tian et al. [Tian, G., Sanders, C. R., Kishi, F., Nakazawa, A., & Tsai, M.-D. (1988) Biochemistry 27, 5544-5552] on the effect of replacement of the conserved His-36 in the cytosolic AK (AK1) from chicken by glutamine and asparagine, this shows that residues 28 of AK from E. coli (AKec) and 36 of AK1 are situated in a comparable environment and are not essential for catalytic activity. PMID- 2223776 TI - Structurally and catalytically important residues in the phosphate binding loop of adenylate kinase of Escherichia coli. AB - Amino acids in the phosphate binding loop of adenylate kinase of Escherichia coli were mutated by site-directed mutagenesis. The mutant proteins with a Pro-9--- Gly (P9G) and with a Lys-13----Gln (K13Q) exchange were overexpressed and purified. They were characterized by steady-state kinetics, fluorescence binding, and structural studies, together with the phosphate binding loop mutants P9L and G10V prepared earlier [Reinstein, J., Brune, M., & Wittinghofer, A. (1988) Biochemistry 27, 4712-4720]. The results obtained show that all these mutations change the structure of the protein as evidenced by NMR spectroscopy and temperature-stability studies. All the mutant proteins have increased dissociation constants for substrates and inhibitors, but their catalytic activity, except for K13Q, is not reduced. The results obtained with K13Q suggest that this lysine residue, which is conserved in all guanine and many adenine nucleotide proteins, might have an important role in catalysis. PMID- 2223777 TI - Complexes of Escherichia coli adenylate kinase and nucleotides: 1H NMR studies of the nucleotide sites in solution. AB - One- and two-dimensional nuclear magnetic resonance (NMR) studies, in particular substrate--protein nuclear Overhauser effect (NOESY) measurements, as well as nucleotide and P1,P5-bis-(5'-adenosyl) pentaphosphate (AP5A) titrations and studies of the temperature-dependent unfolding of the tertiary structure of Escherichia coli adenylate kinase (AKEC) were performed. These experiments and comparison with the same type of experiments performed with the porcine enzyme [Rosch, P., Klaus, W., Auer, M., & Goody, R. S. (1989) Biochemistry 28, 4318 4325] led us to the following conclusions: (1) At pH 8 and concentrations of approximately 2.5-3 mM, AKEC is partially unfolded at 318 K. (2) ATP.Mg2+ binds to the ATP site with a dissociation constant of approximately 40 microM under the assumption that ATP binds to one nucleotide site only. (3) AP5A.Mg2+ binds to both nucleotide sites and thus simulates the active complex. (4) The ATP.Mg2+ adenine in the AKEC.AP5A.Mg2+ complex is located close to His134 and Phe19. (5) The AKEC "G-loop" with bound ATP.Mg2+ is structurally highly homologous to the loop region in the oncogene product p21 with bound GTP.Mg2+. PMID- 2223778 TI - Catalytic activity of the serine proteases alpha-chymotrypsin and alpha-lytic protease tagged at the active site with a (terpyridine)platinum(II) chromophore. AB - Incubation of alpha-chymotrypsin and alpha-lytic protease with chloro(2,2':6',2'' terpyridine)platinum(II), [Pt(trpy)Cl]+, results in attachment of Pt(trpy)2+ tags at both His 57 and His 40 in the former and His 57 in the latter. The [Pt(trpy)His]2+ chromophores are readily detected and quantitated owing to their characteristic, strong UV absorption. Although the tagging of His 57 modifies the catalytic triad (Ser 195, His 57, and Asp 102) and disrupts the charge relay, the platinated enzymes retain significant esterase and amidase activity for both specific and nonspecific substrates. Unlike suicide inhibitors, which inactivate the enzymes by filling the active site and imitating the tetrahedral intermediate, [Pt(trpy)Cl]+ reacts with a particular amino acid and permits binding of substrates. The kinetic constants for the following are reported: two esters and two amides with alpha-chymotrypsin and an amide with alpha-lytic protease. The kcat values are between 1 and 25% of, and the Km values are a little higher than, the corresponding values for the native enzymes. The catalytic activity is not due to the native enzymes, trypsin, or some zinc containing protease. Activities of the native and of the platinated alpha chymotrypsin depend similarly on pH although the pKa of His 57 is raised to 9.7 upon platination. The platinated enzymes undergo autodigestion slower than do the native enzymes. Because the Pt(trpy)2+ tags are noninvasive, stable, and yet easily removable by thiourea, [Pt(trpy)Cl]+ may be used to retard autodigestion of stored proteolytic enzymes. PMID- 2223779 TI - Hierarchical binding of DNA fragments derived from scaffold-attached regions: correlation of properties in vitro and function in vivo. AB - On its upstream side, the human interferon-beta gene is flanked by a 7-kb SAR (scaffold-attached region) DNA element. The core of this element is determined and subjected to in vitro reassociations with isolated scaffolds. Binding properties of SAR fragments with decreasing length are quantified and related to consensus sequences like the topoisomerase II box and an ATATTT motif. Characteristics as the stoichiometry, affinity, and cooperativity of the binding process are shown to depend on the length of SAR DNA and suggest a model involving a multiple-site attachment to protein scaffolds. We propose a rational approach for predicting the SAR mediated transcriptional enhancements in vivo from their binding properties in a standardized in vitro assay. The efficiency of this approach is demonstrated for a marker (huIFN-beta) and a selector gene (neor). PMID- 2223780 TI - DNA solution conformation via infrared circular dichroism: experimental and theoretical results for B-family polymers. AB - Infrared (vibrational) circular dichroism (VCD) has been observed for the DNA models d(CG)5, poly(dG-dC).poly(dG-dC), poly(dG).poly(dC), poly(dA-dT).poly(dA dT), and poly(dA).poly(dT) in the B-conformation in buffered, aqueous solution. The observed results are quantitatively interpreted in terms of the exciton model for coupled carbonyl stretching vibrational states. PMID- 2223781 TI - Studies of the mechanism of the delta 5-3-ketosteroid isomerase reaction by substrate, solvent, and combined kinetic deuterium isotope effects on wild-type and mutant enzymes. AB - delta 5-3-Ketosteroid isomerase (EC 5.3.3.1) catalyzes the isomerization of delta 5-3-ketosteroids to delta 4-3-ketosteroids by a conservative tautomeric transfer of the 4 beta-proton to the 6 beta-position using Tyr-14 as a general acid and Asp-38 as a general base [Kuliopulos, A., Mildvan, A. S., Shortle, D., & Talalay, P. (1989) Biochemistry 28, 149]. On deuteration of the 4 beta-position (97.0%) of the substrate, kcat(H)/kcat(4 beta-D) is 6.1 in H2O and 6.3 in D2O. The solvent isotope effect, kcat(H2O)/kcat(D2O), is 1.6 for both the 4 beta-H and 4 beta-D substrates. Mutation of Tyr-55 to Phe lowers kcat 4.3-fold; kcat(H)/kcat/4 beta D) is 5.3 in H2O and 5.9 in D2O, and kcat(H2O)/kcat(D2O) with the 4 beta-H and 4 beta-D substrates is 1.5 and 1.7, respectively, indicating concerted general acid base catalysis in either the enolization or the ketonization step of both the wild-type and the Tyr-55----Phe (Y55F) mutant enzymes. An additional slow step occurs with the Y55F mutant. Smaller isotope effects on Km are used to estimate individual rate constants in the kinetic schemes of both enzymes. On deuteration of the 4 alpha-position (88.6%) of the substrate, the secondary isotope effect on kcat/Km corrected for composition is 1.11 +/- 0.02 with the wild-type enzyme and 1.12 +/- 0.02 with the Y55F mutant. These effects decrease to 1.06 +/- 0.01 and 1.07 +/- 0.01, respectively, when the 4 beta-position is also deuterated, thereby establishing these to be kinetic (rather than equilibrium) secondary isotope effects and to involve a proton-tunneling contribution. Deuteration of the 6 position of the substrate (92.0%) produces no kinetic isotope effects on kcat/Km with either the wild-type (1.00 +/- 0.01) or the Y55F mutant (1.01 +/- 0.01) enzyme. Since a change in hybridization from sp3 to sp2 occurs at C-4 only during enolization of the substrate and a change in hybridization at C-6 from sp2 to sp3 occurs only during reketonization of the dienol intermediate, enolization of the substrate constitutes the concerted rate-limiting step. Concerted enolization is consistent with the right angle or antarafacial orientations of Tyr-14 and Asp-38 with respect to the enzyme-bound substrate and with the additive effects on kcat of mutation of these catalytic residues [Kuliopulos, A., Talalay, P., & Mildvan, A. S. (1990) Biophys. J. 57, 39a]. PMID- 2223782 TI - Effect of central-residue replacements on the helical stability of a monomeric peptide. AB - The peptide acetylYEAAAKEARAKEAAAKAamide exhibits the dichroic features characteristic of a monomeric helix/coil transition in aqueous solution. Nineteen variants of this peptide each containing a different residue at position 9 were prepared by solid-phase peptide synthesis and purified by reversed-phase chromatography. The thermal dependence of the far-ultraviolet dichroic spectrum of each of these peptides except that containing proline is characteristic for an alpha-helix/coil transition. The relative stability of the helical forms of these peptides does not correlate with the preference of the variable amino acid to occupy a middle position in a protein helix. It is likely that the specific interactions of the variable residue with its local environment obscure any inherent preference of the residue to reside in an alpha-helix. PMID- 2223783 TI - Sequence-specific 1H NMR assignments and determination of the secondary structure for the activation domain isolated from pancreatic procarboxypeptidase B. AB - Nearly complete sequence-specific 1H NMR assignments are presented for amino acid residues 3-81 in the 81-residue globular activation domain of porcine pancreatic procarboxypeptidase B isolated after limited tryptic proteolysis of the zymogen. These resonance assignments are consistent with the chemically determined amino acid sequence. Regular secondary structure elements were identified from nuclear Overhauser effects and the sequence locations of slowly exchanging backbone amide protons. The molecule contains two alpha-helices, including residues 20-30 and approximately residues 58-72, and a three-stranded antiparallel beta-sheet with the individual strands extending approximately from 12 to 17, 50 to 55, and 75 to 77. The identification of these secondary structures and a preliminary analysis of additional long-range NOE distance constraints show that isolated activation domain B forms a stable structure with the typical traits of a globular protein. The data presented here are the basis for the determination of the complete three dimensional structure of activation domain B, which is currently in progress. PMID- 2223784 TI - Binding and precipitating activities of Lotus tetragonolobus isolectins with L fucosyl oligosaccharides. Formation of unique homogeneous cross-linked lattices observed by electron microscopy. AB - We have recently observed that certain asparagine-linked oligosaccharides are multivalent and capable of binding and precipitating with the D-mannose-specific lectin concanavalin A [cf. Bhattacharyya, L., & Brewer, C. F. (1989) Eur. J. Biochem. 178, 721-726] and with a variety of D-galactose-specific lectins [Bhattacharyya, L., Haraldsson, M., & Brewer, C. F. (1988) Biochemistry 27, 1034 1041]. In the present study, we have examined the binding and precipitating activities of a variety of mono- and biantennary L-fucosyl oligosaccharides with three L-fucose-specific isolectins from Lotus tetragonolobus, LTL-A, LTL-B, and LTL-C. The results show that certain difucosyl biantennary oligosaccharides are capable of cross-linking and precipitating with tetrameric isolectins, LTL-A and LTL-C, but not with dimeric isolectin, LTL-B. Quantitative precipitation analyses show that biantennary oligosaccharides containing the Lewis(x) antigen (or type 2 chain of Lewis(a)), Gal beta (1-4)[Fuc alpha (1-3)]GlcNAc, at the nonreducing terminus of each arm are bivalent ligands. However, a biantennary oligosaccharide containing a Lewis(x) determinant on one arm and a type 2 chain of blood group H(O) determinant, Fuc alpha (1-2)Gal beta (1-4)GlcNAc, on the other arm and a monoantennary oligosaccharide containing two fucose residues (analogue of the Lewis(y) antigen) bind but do not precipitate with the isolectins, indicating that the positions and linkage of fucose residues are critical for cross linking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223785 TI - Isopentenyldiphosphate:dimethylallyldiphosphate isomerase: construction of a high level heterologous expression system for the gene from Saccharomyces cerevisiae and identification of an active-site nucleophile. AB - Isopentenyldiphosphate:dimethylallyldiphosphate isomerase (IPP isomerase) is an enzyme in isoprene metabolism which catalyzes the interconversion of the fundamental five-carbon homoallylic and allylic diphosphate building blocks for the pathway. The gene encoding IPP isomerase has recently been isolated from Saccharomyces cerevisiae [Anderson, M. S., Muehlbacher, M., Street, I.P., Proffitt, J., & Poulter, C. D. (1989) J. Biol. Chem. 264, 19169-19175]. A heterologous expression system was constructed for the gene and used to overexpress IPP isomerase in Escherichia coli. In transformants carrying the expression vector, IPP isomerase activity was increased by over 100,000-fold relative to that of the untransformed host strain. The overexpressed enzyme constitutes 30-35% of the total soluble cell protein and can be purified to homogeneity in two steps. Recombinant IPP isomerase was indistinguishable from that purified from yeast. 3-(Fluoromethyl)-3-butenyl diphosphate (FIPP) is a specific active-site-directed inhibitor of IPP isomerase from Claviceps purpurea [Muehlbacher, M., & Poulter, C. D. (1988) Biochemistry 27, 7315-7328]. Inactivation of yeast IPP isomerase by FIPP was active-site-directed, and inhibition resulted in formation of a stoichiometric enzyme-inhibitor complex. The site of covalent attachment in the enzyme-inhibitor complex was determined by inactivating IPP isomerase with [4-3H]FIPP, followed by digestion of the labeled enzyme with trypsin and purification of the resulting radioactive peptides by reversed-phase high-performance liquid chromatography. The primary site of attachment was Cys-139. PMID- 2223786 TI - Identification and purification of the carnitine carrier from rat liver mitochondria. AB - The carnitine carrier from rat liver mitochondria, solubilized in Triton X-100 and partially purified on hydroxyapatite, was identified and completely purified by specific elution from celite in the presence of cardiolipin. On SDS-gel electrophoresis, the purified celite fraction consisted of a single band with an apparent Mr of 32,500. When reconstituted into liposomes the carnitine transport protein catalyzed an N-ethylmaleimide-sensitive carnitine/carnitine exchange. It was purified 970-fold with a recovery of 43% and a protein yield of 0.04% with respect to the mitochondrial extract. The properties of the reconstituted carrier, i.e., requirement for a countersubstrate, substrate specificity and inhibitor sensitivity, were similar to those of the carnitine transport system as characterized in intact mitochondria. PMID- 2223787 TI - Temperature dependence of the ripple structure in dimyristoylphosphatidylcholine studied by synchrotron X-ray small-angle diffraction. AB - The ripple structure of 1,2-dimyristoyl-L-phosphatidylcholine (DMPC) multibilayer containing excess water (60 wt%) was studied by synchrotron X-ray small-angle diffraction. The (0,1) spacing which corresponds to the ripple repeat distance depends on temperature: At 13 degrees C the (0,1) spacing is 14.15 nm, the spacing decreases at higher temperatures and reaches 12.1 nm at 23.5 degrees C, just below the main transition temperature. The spacing is in good agreement between heating process and cooling process except for the supercooling region. The result suggests that the rearrangement of the ripple structure takes place during temperature change successively. The Landau-de Gennes free energy equation explains well the temperature dependence of the ripple repeat distance. PMID- 2223788 TI - Insertion of bacteriorhodopsin into polymerized diacetylenic phosphatidylcholine bilayers. AB - We have developed a method to incorporate the membrane protein bacteriorhodopsin into polymerized bilayers composed of a diacetylenic phosphatidylcholine, 1,2 bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) and a non polymerizable phospholipid, dinonanoylphosphatidylcholine (DNPC). The extent of DC8,9PC polymerization in the bilayer was significantly improved when 2:1 mole ratio DNPC-DC8,9PC was used. Octyl glucopyranoside-solubilized bacteriorhodopsin was inserted into the polymerized DNPC-DC8,9PC bilayers by overnight incubation at 4 degrees C followed by dialysis to remove the detergent. The protein was inserted into the membranes after photo-polymerization to avoid inactivation of the protein due to the UV irradiation. The insertion of bacteriorhodopsin into the polymerized DNPC-DC8,9PC membranes was confirmed by density gradient centrifugation, UV/visible spectroscopy, and freeze fracture electron microscopy. The polymerized DNPC-DC8,9PC membranes containing bacteriorhodopsin were about 10% protein by weight. These results suggest that mixed lipid systems such as the DNPC-DC8,9PC can be used to improve both the extent of polymerization and the efficiency of membrane protein incorporation in the polymerized bilayer. PMID- 2223789 TI - Specific electropermeabilization of leucocytes in a blood sample and application to large volumes of cells. AB - Electropermeabilization is obtained when the membrane potential difference reaches a critical threshold. This is performed by submitting cells to an external electric field pulse. The field modulates the endogenous potential difference in a cell-size-dependent way. Computer simulations predict that large cells would be specifically permeabilized in a mixture with smaller cells. This was examined on a mixture of Chinese hamster ovary (CHO) cells and erythrocytes. CHO cells were permeabilized to Trypan blue without any occurrence of haemolysis. A similar 'size' specificity was observed on blood samples. This agreement between prediction and experimental observation indicates that induction of electropermeabilization is mainly under the control of the size of the target cell. Its physiology plays only a minor role, if any. Treating blood with 10 square wave pulses lasting 100 microseconds of an intensity of 1.6 kV/cm induced the permeabilization of 70% of the leucocytes (polymorphs and monocytes) but did not affect erythrocytes. No washing of the sample was needed in a procedure in which cells were pulsed in the plasma. A flow electropulsing process allows the treatment of large blood volumes under conditions where cells are kept viable. These results show that electropermeabilization could be used as an effective way to obtain immunocompatible drug vehicles. PMID- 2223790 TI - Transport overshoot during 2-methyl-4-amino-5-hydroxymethylpyrimidine uptake by Saccharomyces cerevisiae. AB - The transport overshoot during 2-methyl-4-amino-5-hydroxymethylpyrimidine (hydroxymethylpyrimidine) uptake by the thiamin transport system in Saccharomyces cerevisiae was investigated. The overshoot was found to be temperature- and energy-dependent and affected by the growth phase of the yeast. The efflux system for hydroxymethylpyrimidine appeared to be more sensitive to 2,4-dinitrophenol than the influx system, resulting in the loss of the overshoot of the pyrimidine in the presence of the uncoupler. Furthermore, the overshoot did not occur after the preincubation of yeast cells with inhibitors of protein synthesis such as cycloheximide and anisomycin. These results suggest that an active efflux system for hydroxymethylpyrimidine, which is rapidly synthesized, is involved in the overshoot of this pyrimidine during its transport in S. cerevisiae. PMID- 2223791 TI - Influence of amino acid side-chain modification on the uptake system for beta lactam antibiotics and dipeptides from rabbit small intestine. AB - The influence of chemical modification of functional amino acid side-chains in proteins on the H(+)-dependent uptake system for orally active alpha-amino-beta lactam antibiotics and small peptides was investigated in brush-border membrane vesicles from rabbit small intestine. Neither a modification of cysteine residues by HgCl2, NEM, DTNB or PHMB and of vicinal thiol groups by PAO nor a modification of disulfide bonds by DTT showed any inhibition on the uptake of cephalexin, a substrate of the intestinal peptide transporter. In contrast, the Na(+)-dependent uptake systems for D-glucose and L-alanine were greatly inhibited by the thiol modifying agents. With reagents for hydroxyl groups, carboxyl groups or arginine the transport activity for beta-lactam antibiotics also remained unchanged, whereas the uptake of D-glucose and L-alanine was inhibited by the carboxyl specific reagent DCCD. A modification of tyrosine residues with N-acetylimidazole inhibited the peptide transport system and did not affect the uptake systems for D-glucose and L-alanine. The involvement of histidine residues in the transport of orally active alpha-amino-beta-lactam antibiotics and small peptides (Kramer, W. et al. (1988) Biochim. Biophys. Acta 943, 288-296) was further substantiated by photoaffinity labeling studies using a new photoreactive derivative of the orally active cephalosporin cephalexin, 3-[phenyl-4-3H]azidocephalexin, which still carries the alpha-amino group being essential for oral activity. 3 Azidocephalexin competitively inhibited the uptake of cephalexin into brush border membrane vesicles. The photoaffinity labeling of the 127 kDa binding protein for beta-lactam antibiotics with this photoprobe was decreased by the presence of cephalexin, benzylpenicillin or dipeptides. A modification of histidine residues in brush-border membrane vesicles with DEP led to a decreased labeling of the putative peptide transporter of Mr 127,000 compared to controls. This indicates a decrease in the affinity of the peptide transporter for alpha amino-beta-lactam antibiotics by modification of histidine residues. The data presented demonstrate an involvement of tyrosine and histidine residues in the transport of orally active alpha-amino-beta-lactam antibiotics across the enterocyte brush-border membrane. PMID- 2223792 TI - Determination of cell membrane passive electrical properties using frequency domain dielectric spectroscopy technique. A new approach. AB - To take into account the highly irregular surface morphology of cell membranes we have analyzed impedance measurements of biological cell suspensions in general terms using a fractal description of the surface roughness of the cell membrane. This analysis has been applied to human erythrocytes in different solutions of alkaline metal salts and to human lymphocytes, since these cells present a different surface irregularity. The passive electrical properties (dielectric constant and electrical conductivity) deduced from conductivity measurements at radiowave frequencies have been discussed on the basis of the fractal dimension of the membrane surface. PMID- 2223793 TI - Interleukin-2 binds to gangliosides in micelles and lipid bilayers. AB - Gangliosides shed from the surface of tumour cells may be involved in tumour induced immunosuppression. These anionic sialoglycolipids are known to be potent inhibitors of lymphocyte proliferation, and it has been suggested that they interfere with processes mediated by the growth factor interleukin-2 (IL-2). We have thus investigated the interaction of IL-2 with gangliosides in micelles and lipid bilayers. Gel filtration FPLC showed that 125I-IL-2 can bind to micellar gangliosides in aqueous solution, and this interaction was strongly promoted by low concentrations of serum. Binding to ganglioside micelles was specific in that it required a native IL-2 molecule. IL-2 binding remained unchanged in the presence of 40% ethylene glycol, suggesting that it was not due to hydrophobic interactions. Ganglioside oligosaccharides alone were not able to bind to IL-2. Direct binding studies and gel filtration chromatography indicated that both multilamellar liposomes and 100 nm unilamellar vesicles containing gangliosides were able to interact with IL-2. Bilayers of lipid alone showed no binding. The interaction of IL-2 with bilayer gangliosides was highly dependent on the bilayer lipid composition, but appeared independent of lipid phase state. These results suggest that gangliosides may be a physiologically relevant target for IL-2 binding. PMID- 2223794 TI - Ethanol induces interdigitated gel phase (L beta I) between lamellar gel phase (L beta') and ripple phase (P beta') in phosphatidylcholine membranes: a scanning density meter study. AB - Effects of ethanol on dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC) dispersions were investigated with an automated scanning density meter and a differential scanning calorimeter (DSC). The temperature-dependent profile of specific volume measured by the density meter clearly exhibited phase transitions of the DPPC and the DSPC dispersions as drastic changes in the thermal expansion coefficients. On increasing the ethanol concentration in the DPPC dispersions, the pretransition temperature was reduced faster than the main transition temperature was. An interdigitated gel phase (L beta I) appeared as a region of lower specific volume at the pretransition temperature when the ethanol concentration reached 40 mg/ml. The L beta I phase spread both its ends in an ethanol-dependent fashion, and the high-temperature end merged to the main transition at 50 mg/ml of ethanol. The temperature-ethanol phase diagram has been determined for DPPC. The transitions L beta' to L beta I and from L beta I to P beta' were also observed on the thermograms of DSC measurements. In the DSPC dispersions, the L beta I phase was induced between the L beta' and the P beta' phases by a lower ethanol concentration (about 20 mg/ml). PMID- 2223795 TI - Inhibition of autoxidation of egg yolk phosphatidylcholine in homogenous solution and in liposomes by oxidized ubiquinone. AB - The aim of this study was to obtain a quantification of the antioxidant activity of ubiquinone. To this purpose the oxidation of egg yolk phosphatidylcholine both in solvent and in liposomes initiated by an azocompound has been studied either in the absence or in the presence of ubiquinone-3, using alpha-tocopherol as a reference antioxidant. The two experimental systems gave similar results. In the presence of ubiquinone-3 the oxidation rate was reduced with respect to control experiments but was faster than that in the presence of alpha-tocopherol. The amount of ubiquinone required to decrease the autoxidation rate was so high as to prevent detection of the induction period. The stoichiometric factor was greater than 2 and the rate constant of inhibition was two orders of magnitude lower than that of alpha-tocopherol. It is concluded that high concentrations of ubiquinone are required to exhibit significant antioxidant activity. A possible mechanism compatible with the stoichiometric factor larger than 2 for the inhibiting effect of ubiquinone is also suggested. PMID- 2223796 TI - Na(+)-ionophore, monensin-induced rise in cytoplasmic free calcium depends on the presence of extracellular calcium in FRTL-5 rat thyroid cells. AB - Calcium is an important regulator of cell function, and may be influenced by the intracellular sodium content. In the present study, the Na(+)-ionophore, monensin, was used to investigate the interrelationship between changes in intracellular Na+ concentration ([Na+]i) and elevation of cytosolic Ca2+ concentration ([Ca2+]i) in FRTL-5 thyroid cells. Cytoplasmic Ca2+ levels were measured using the fluorescent dye, indo-1. Monensin induced a dose-dependent increase in [Ca2+]i in FRTL-5 cells. Inhibitors of intracellular Ca2+ release, TMB-8 and ryanodine, were unable to prevent the monensin effect on [Ca2+]i. The alpha 1-receptor antagonist, prazosin, did not block the monensin-stimulated increase in [Ca2+]i. In the absence of extracellular calcium there was a marked diminution in the monensin effect on [Ca2+]i, yet calcium channel antagonists (nifedipine, diltiazem and verapamil) did not inhibit the response. Replacement of Na+ by choline chloride in the medium depressed the monensin-evoked rise in [Ca2+]i by up to 84%. Furthermore, addition of the Na(+)-channel agonist, veratridine, elicited an increase in [Ca2+]i, even though less dramatic than that caused by monensin. Ouabain increased the resting cytosolic Ca2+ concentration as well as the magnitude of the monensin effect on [Ca2+]i. The absence of any effect on the Na(+)-ionophore evoked increase in [Ca2+]i upon addition of tetrodotoxin (TTX) excluded a possible involvement of TTX-sensitive Na+ channels. These data show that the rise in [Ca2+]i induced by increasing [Na+]i is largely dependent on both external Na+ and Ca2+. Calcium entry appears not to involve voltage-dependent or alpha 1-receptor sensitive Ca2+ channels, but may result from activation of an Na(+)-Ca2+ exchange system. PMID- 2223797 TI - Two different types of lysis of chromaffin granules characterised by freeze fracture electron microscopy and photon correlation spectroscopy. AB - When bovine chromaffin granules are incubated in hyperosmolar sucrose solutions and subsequently transferred back towards isoosmolarity they undergo lysis ('hyperosmotic relaxation lysis'). This type of lysis was compared with the common effect of hypotonic lysis by means of photon correlation spectroscopy (PCS) and freeze-fracture electron microscopy. Both methods revealed differences regarding mean sizes and size distributions of granules lysing under either hypotonic or hypertonic conditions. However, the results obtained by these two methods were not consistent. In the case of hypotonic lysis, a nonmonotonic behaviour of the mean diameter as a function of the sucrose concentration was observed by PCS, but not in the micrographs. From EM size determinations we obtained a decrease in the mean diameter and an increase of the width of the distribution due to the appearance of small (50-200 nm) vesicles. Probably these vesicles are intragranular vesicles released during lysis. The maximum in photon correlation spectroscopy (PCS) diameter being 140% of the isotonic diameter is shown to be caused by the changing size distribution and geometry of the lysing granules. In the case of hyperosmotic relaxation, micrographs revealed that originally shrunken, nonspherical granules regained their spherical shape and formed small (60 nm) vesicles upon lysis. In contrast, no difference was observed between the sizes of granules prior to and after hyperosmotic relaxation by means of PCS. The paper discusses the validity of intensity-weighted light scattering data of polydisperse particle suspensions with changing size distributions. The mechanism of hyperosmotic relaxation lysis is considered. PMID- 2223798 TI - The effects of the extracellular manganese concentration and variation of the interpulse delay time in the CPMG sequence on water exchange time across erythrocyte membranes. AB - There has been broad disagreement in the literature regarding the dependence of water exchange times (Te) across erythrocyte membranes studied by the 1H-NMR Carr Purcell-Meiboom-Gill (CPMG) pulse sequence on extracellular Mn2+ concentration. While some workers saw no change in Te with Mn2+, others reported a 35-50% decrease in Te with this extracellular paramagnetic relaxation agent. We present 1H-NMR evidence that a 30-50% change in Te can be produced by interdependence of the interpulse delay time of the CPMG pulse sequence and the external Mn2+ concentration. Such a large dependency is interpreted in terms of the diffusional effect as a major source. However, it is shown experimentally that if a large number of refocusing pi pulses are used, the observed transverse relaxation times are unaffected by Mn2+. Under these conditions excellent agreement of Te obtained in our study (13.0 +/- 0.64 ms (N = 36) at 21 degrees C) and that of 12.8 +/- 3.6 ms at 20-23 degrees C reported by the radiotracer method was found. Our findings suggest new and important implications for evaluating the previous reports of the 1H-NMR CPMG method concerning the [Mn2+] effect in the decrease of Te, and provide conditions where studies of water transport across erythrocyte membranes using this magnetic resonance method can be used with confidence. PMID- 2223799 TI - Chromatographic characterization of nitrobenzylthioinosine binding proteins in band 4.5 of human erythrocytes: purification of a 40 kDa truncated nucleoside transporter. AB - DEAE-column-purified band 4.5 polypeptides of human erythrocyte membranes are mostly glucose transporters with nucleoside transporters as a minor component. The purpose of the present work was to differentially identify and isolate the nucleoside transporters in band 4.5 free from glucose transporters. Equilibrium binding studies demonstrated that the band 4.5 preparation binds nibrobenzylthioinosine (NBTI), a potent nucleoside transport inhibitor, at two distinct sites, one with a high affinity (dissociation constant, KD of 1 nM) with a small capacity, BT (0.4 nmol/mg protein), and the other with a low affinity (KD of 15 microM) with a large BT (14-16 nmol/mg protein). The BT of the low-affinity site was equal to that of the cytochalasin B binding site in the preparation. A gel-filtration chromatography of band 4.5 photolabeled with [3H]NBTI and [3H]cytochalasin B identified three polypeptides of apparent Mr 55,000, 50,000 and 40,000. Of these, the 55 kDa polypeptide was specifically labeled by cytochalasin B (p55GT), indicating that it is a glucose transporter. Both the 50 and 40 kDa polypeptides were labeled with NBTI at low ligand concentrations (less than 0.1 microM), which was abolished by an excess (20 microM) of nitrobenzylthioguanosine, indicating that they are two forms (p50NT and p40NT, respectively) of the high affinity NBTI binding protein or nucleoside transporter. At higher (not less than 10 microM) NBTI concentrations, however, p55GT was also labeled with NBTI, indicating that the low-affinity NBTI binding is due to a glucose transporter. Treatment of band 4.5 with trypsin reduced the p50NT labeling with a concomitant and stoichiometric increase in the p40NT NBTI labeling without affecting the high-affinity NBTI binding of the preparation. These findings indicate that the nucleoside transporter is slightly smaller in mass than the glucose transporter and that trypsin digestion produces a truncated nucleoside transporter of apparent Mr 40,000 which retains the high-affinity NBTI binding activity of intact nucleoside transporter. Both p55GT and p50 NT were coeluted in a major protein fraction, P1 in the chromatography, while p40NT was eluted separately as a minor protein fraction, P1a. All three polypeptides formed mixed dimers, which were eluted in a fraction PO. We have purified and partially characterized the truncated nucleoside transporter, p40NT. The purified p40NT may be useful for biochemical characterization of the nucleoside transporter. PMID- 2223800 TI - Characterization of Na(+)-dependent, active nucleoside transport in rat and mouse peritoneal macrophages, a mouse macrophage cell line and normal rat kidney cells. AB - Peritoneal rat macrophages expressed solely an Na(+)-dependent, concentrative nucleoside transporter, which possesses a single Na(+)-binding site and transports purine nucleosides and uridine but not thymidine or deoxycytidine. The Michaelis-Menten constants for formycin B and Na+ were about 6 microns and 14 mM, respectively, and the estimated Na+:formycin B stoichiometry was 1:1. Rat macrophages accumulated 5 microM formycin B to a steady-state level exceeding that in the medium by about 500-fold during 60 min of incubation at 37 degrees C. Concentrative formycin B transport was resistant to inhibition by nitrobenzylthioinosine, lidoflazine, dilazep and nifedipine, but was slightly inhibited by high concentrations of dipyridamole (greater than 10 microM) and probenecid (greater than 100 microM). Mouse peritoneal macrophages and lines of mouse macrophages and normal rat kidney cells expressed Na(+)-dependent, active nucleoside transport but in addition significant Na(+)-independent, facilitated nucleoside transport. Facilitated nucleoside transport in these cells was sensitive to inhibition by nitrobenzylthioinosine, dilazep and dipyridamole. The presence of these inhibitors greatly enhanced the concentrative accumulation of formycin B by these cells by inhibiting the efflux via the facilitated transporter of the formycin B actively transported into the cells. Whereas rat macrophages lacked high-affinity nitrobenzylthioinosine-binding sites, mouse macrophages and normal rat kidney cells possessed about 10,000 such sites/cell. Rat and mouse erythrocytes, rat lymphocytes, and lines of Novikoff rat hepatoma cells, Chinese hamster ovary cells, Mus dunni cells and embryonic monkey kidney cells expressed only facilitated nucleoside transport. PMID- 2223801 TI - Lamellar packing of a chiral N,N-dimethylphosphatidylethanolamine: electron diffraction. Evidence for a lecithin-type headgroup conformation. AB - Lamellar electron diffraction intensity data from epitaxially crystallized 1,2 dipalmitoyl-sn-glycerophospho-N,N-dimethylethanolamine were used to determine the layer packing in order to compare the chiral structure to the crystal structure of a racemic homologue. After finding the chain orientation, the structure was determined by interpretation of the Patterson function, followed by independent crystallographic phase assignments with conventional direct methods (use of three phase structure invariants). The phase determination was verified by a translational search with a molecular model based on a similar lecithin structure. The final R-value is 0.29, and this is lowered to 0.18 after a correction is made for incoherent multiple electron scattering. The layer packing is found to be very much like that of a diacyl phosphatidylcholine with the N,N dimethylethanolamine moiety parallel to the bilayer surface rather than the perpendicular arrangement of headgroups involved in an interdigitated layer, as seen for racemic homolog. PMID- 2223802 TI - Unequal distribution of membrane components between pseudopodia and cell bodies of platelets. AB - Platelet pseudopodia were compared to platelet cell bodies with respect to their lipid composition, fatty acid distribution and protein composition. The methodology for producing pseudopodial preparations of platelets stimulated with thrombin, ADP or calcium ionophore was established. The separation of pseudopodia and cell bodies was verified by electron microscopic examination of the respective platelet components. Lipid analyses demonstrated a preponderance of lysophospholipids and sphingomyelin in pseudopodial preparations and a large increase in mono-, di- and tri-ene fatty acids as compared to cell bodies. Changes were also evident in the protein composition evaluated by one- and two dimensional SDS-polyacrylamide gel electrophoresis and by [32P]ATP labeling of exofacial membrane proteins. A protein of approximately 68 kDa which reacted strongly with antibody to PlA1, was prominantly displayed in platelet pseudopodia. Thus, our studies demonstrate a heterogeneous distribution of lipids and proteins in a mammalian membrane system which may have important implications for the functional behavior of the cell. PMID- 2223803 TI - Effects of divalent cations on lipid flip-flop in the human erythrocyte membrane. AB - Treatment of human erythrocytes with ionophore A23187 (10 mumol.l-1) and Ca2+ (0.05-0.5 mmol.l-1) or Sr2+ (0.2-1 mmol.l-1) in results in a concentration dependent acceleration of the transmembrane reorientation (flip) of the lipid probes lysophosphatidylcholine and palmitoylcarnitine to the inner membrane leaflet after their primary insertion into the outer leaflet. Mg2+, Mn2+, Zn2+ and La3+ do not accelerate flip. Ca2(+)-induced flip acceleration depends also on the ionophore concentration. It is reversed by removal of Ca2+ with EDTA. A causal role of Ca2(+)-induced membrane protein degradation and decrease of the polyphosphoinositide level in flip acceleration could be excluded. Likewise, calmodulin-dependent processes are probably not involved since the calmodulin antagonist calmidazolium (2-10 mumol.l-1) does not suppress but even enhances the Ca2(+)-induced flip acceleration. The same is true for the Ca2+ antagonist flunarizine. These drugs do not alter flip rate in the absence of Ca2+. At high Ca2+ (1-5 mmol.l-1) an initial flip acceleration is followed by flip normalization. High concentrations of Mn2+ and Mg2+ slow down flip rates. The selective acceleration of flip by Ca2+ and Sr2+ is discussed to be due to a local detachment of the membrane skeleton from the bilayer, whereas the unselective slow down of flip by divalent cations might be due to a stabilization of the membrane bilayer by the cations. After loading of cells with Ca2+ (but not with Mn2+) the inner membrane leaflet phospholipid phosphatidylserine becomes rapidly exposed to the outer membrane surface, as detectable by its accessibility to phospholipase A2 (5 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223804 TI - Selectivity of lipid-protein interaction with myelin proteolipids PLP and DM-20. A fluorescence anisotropy study. AB - The two main myelin proteolipids, PLP (30 kDa) and DM-20 (25 kDa), differ by an internal deletion in DM-20. The deleted fragment, of 35 amino acids (116-150), corresponds to the major hydrophilic domain of PLP. Fluorescence anisotropy experiments using diphenylhexatriene as a fluorescent probe were performed to detect the phase separation induced by these two proteolipids in multilamellar vesicles of binary composition. We found that in vesicles composed of 30% L-alpha PS and 70% DPPC, the PLP boundary layer contained about 18 motionally restricted phospholipids, almost exclusively L-alpha-PS. On the contrary, the DM-20 boundary layer contained only 14 to 15 phospholipids, with a composition no different from that of the bulk vesicle. In mixtures of DMPG and DPPC, the selectivity of PLP for the acidic phospholipid DMPG was maintained, but was lower than that observed for L-alpha-PS. We assume that this selectivity of PLP stems mainly from electrostatic interactions between the charged residues of the 116-150 fragment, deleted in DM-20, and the acidic phospholipids. These results suggest that fragment 116-150 may play a specific role in the interaction of PLP with the lipid bilayer of the myelin membrane. PMID- 2223805 TI - A solid-solution theory of anesthetic interaction with lipid membranes: temperature span of the main phase transition. AB - Anesthetics (or any other small additives) depress the temperature of the main phase transition of phospholipid bilayers. Certain anesthetics widen the temperature span of the transition, whereas others do not. The widening in a first-order phase transition is intriguing. In this report, the effects of additive molecules on the temperature and its span were explained by the solid solution theory. By assuming coexistence of the liquid-crystal and solid-gel phases of lipid membranes at phase transition, the phase boundary is determined from the distribution of anesthetic molecules between the liquid-crystal membrane versus water and between the solid-gel membrane versus water. The theory shows that when the lipid concentration is large or when the lipid solubility of the drug is large, the width of the transition temperature increases, and vice versa. Highly lipid-soluble molecules, such as long-chain alkanols and volatile anesthetics, increase the width of the transition temperature when the lipid:water ratio is large, whereas highly water-soluble molecules, such as methanol and ethanol, do not. The aqueous phase serves as the reservoir for anesthetics. Depletion of the additive molecules from the aqueous phase is the cause of the widening. When the reservoir capacity is large, the temperature width does not increase. The theory also predicts asymmetry of the specific heat profile at the transition. PMID- 2223806 TI - Antioxidant activity of probucol and its effects on phase transitions in phosphatidylcholine liposomes. AB - The effect of probucol on the phase behavior of dimyristoylphosphatidylcholine (DMPC) was examined by fluorescence polarization and differential scanning calorimetry (DSC). Probucol broadens and shifts the temperature of the main phase transition of DMPC liposomes as measured by fluorescence polarization with diphenylhexatriene and trimethyl-ammonium-diphenylhexatrine at concentrations as low as 5 mole%. As measured by DSC, probucol reduces the transition temperature of the gel----liquid-crystalline phase transition of DMPC by approx. 2 C degrees at all concentrations above about 5 mole% probucol and eliminates the pretransition at less than 1 mole%. In addition, the phase transition of DMPC is broadened and the enthalpy of the transition reduced by approx. 50%. Even at high concentrations of probucol, the gel----liquid-crystalline phase transition of DMPC is not eliminated. Similar effects are observed with dipalmitoylphosphatidylcholine liposomes. Based on these DSC measurements, measurements of the melting of probucol in dry mixtures with DMPC and observations of probucol mixtures with DMPC under polarizing optics, the maximum solubility of probucol in DMPC is approx. 10 mole%. This concentration exceeds that required (approx. 0.5 mole%) to prevent peroxidation of 10 mole% arachidonic acid in DMPC liposomes for 30 min in the presence of 0.05 mM Fe(NH4)(SO4)2 at 4 degrees C. Thus, probucol has a limited solubility in saturated phosphatidylcholine bilayers, but is an effective antioxidant at concentrations lower than its maximum solubility. PMID- 2223807 TI - Action potential duration and activation of ATP-sensitive potassium current in isolated guinea-pig ventricular myocytes. AB - It is difficult to associate the ATP-sensitive potassium (K-ATP) channel of cardiac muscle with hypoxia/ischemia induced action potential shortening because this occurs before intracellular ATP falls to levels associated in vitro with channel opening. This leaves the cardiac K-ATP channel without any obvious physiological function. We have quantitatively examined the relationship between action potential duration and K-ATP channel activity in enzymatically isolated ventricular myocytes of the guinea-pig. In whole-cell voltage-clamp recording experiments when the K-ATP channel opener SR 44866 (2-10 microM) stimulated an outward membrane current greater than 50 pA at 0 mV membrane potential (the equivalent of 30 open K-ATP channels or 1% of the cell K-ATP channel population) action potential duration was reduced by more than 50%. In the majority of cell attached membrane patch recordings metabolic inhibition stimulated K-ATP channel open probability of 1-2% which continued for long periods (7-25 min) before cell contracture and coincident major K-ATP channel activation (open probability 65%). Our quantitative analysis thus shows that physiologically relevant activity of K ATP channels in cardiac muscle is confined to a very small percentage of the possible cell K-ATP current and thus intracellular ATP would not have to fall very far before the opening of K-ATP channels would influence cardiac excitability. PMID- 2223808 TI - Formation of the antiplanar-antiplanar phosphate conformation of dilauroylphosphatidylcholine bilayers. AB - Infrared spectroscopy was used to investigate lipid conformational changes that occur in dilauroylphosphatidylcholine (diC12PC) bilayers with and without fatty acid-amino-acids as guest molecules in the membrane. Incorporating 2.5 mole% N decanoylglycine (decgly) into diC12PC liposomes caused formation of the antiplanar-antiplanar (ap-ap) phosphodiester conformation which was stable in room temperature IR spectra. Several other fatty-acid-amino-acids incorporated into diC12PC bilayers were found to also elicit the ap-ap phosphodiester conformation. Unlike these diC12PC/fatty-acid-amino-acid mixed bilayers, pure diC12PC bilayers would form the ap-ap phosphodiester conformation only under low temperature incubation conditions. Dry diC12PC films incubated at 5 degrees C for 0.5 h (brief incubation) or 16 h (prolonged incubation), and then rapidly hydrated (i.e., vortexed at 25 degrees C in D2O), caused the ap-ap phosphodiester conformation to persist in the diC12PC liposomes equilibrated to room temperature. Slow hydration for 16 h at 5 degrees C in both buffered and non buffered D2O of diC12PC lipid films also produced the ap-ap phosphodiester conformation. In contrast, slow hydration for 16 h at 5 degrees C in PBS/D2O of diC12PC/decgly mixed films caused the greatest number of ap-ap phosphodiester conformers. Using pure diC12PC bilayers, infrared data indicate that incubation of diC12PC films causes the headgroup phosphodiester conformation to change from gauche-gauche (g-g) conformation to the ap-ap conformation. Under all liposome formation conditions examined, no changes in hydration of either the phosphate group or the carbonyl ester group were detected and in addition, no trans/gauche conformational changes in the acyl chain were observed. PMID- 2223810 TI - Biomembrane-modulated, lysosomal phospholipase A2 contamination of chromaffin granule ghosts. AB - It was reported that subcellular fractionation of bovine adrenal medulla results in the separation of distinct, non-calcium-dependent phospholipases A2--one associated with chromaffin granule ghosts, another with lysosomes. The basis of this distinction is pH optimum: in routine assays utilizing neat liposomal substrates, the chromaffin granule ghost-associated enzyme is alkaline-active whereas the lysosomal enzyme is acid-active (Husebye, E.S. and Flatmark, T. (1987) Biochim. Biophys. Acta 920, 120-130). We now report that biomembranes after liposomal substrates and/or lysosomal phospholipase A2 such that the enzyme now hydrolyzes them (at low cation concentration) with an alkaline pH optimum. In a lysosomal membrane fraction, phospholipase A2 activity at pH 7.5 relative to activity at pH 5.0 increases as increasing amounts of lysosomal membranes are assayed. The pH optimum of chromaffin granule ghost-associated phospholipase A2 toward liposomal substrates is likewise biomembrane-dependent and, when assayed carefully, is indistinguishable on the basis of optimal pH from the lysosomal enzyme. Although chromaffin granule ghost-associated phospholipase A2 is most likely a lysosomal contaminant, its broad, biomembrane-modulated pH range may still allow it to participate in catecholamine secretion. More importantly, however, sensitivity of adrenal medullary lysosomal phospholipase A2 to biomembranes broadens its potential physiologic pH range and may also play a role in the regulation of this potentially deleterious activity. PMID- 2223809 TI - Increased aminophospholipid translocase activity in human platelets during secretion. AB - Fluorescent labeled analogs of phosphatidylcholine (NBD-PC) and phosphatidylserine (NBD-PS) were used to study transport of phospholipids from the outer to the inner leaflet of the plasma membrane of human platelets. Platelets were stimulated with thrombin or Ca2(+)-ionophore at various extracellular [Ca2+]. No significant transport of NBD-PC could be observed either in resting or stimulated platelets. NBD-PS transport in platelets stimulated with thrombin (with or without extracellular Ca2+), or ionophore in the presence of EGTA, was enhanced 4-fold (t1/2 approximately 2 min) compared to unstimulated controls (t1/2 approximately 8 min). Stimulation with ionophore at extracellular [Ca2+] exceeding 8 microM caused a gradual decrease in inward transport of NBD PS. At 100 microM Ca2+, NBD-PS transport becomes as slow as that of NBD-PC. We conclude that platelet activation by agonists that induce secretion without appreciable shedding is accompanied by an increase in translocase activity that maintains asymmetry during fusion which occurs during exocytosis. PMID- 2223811 TI - The influence of general, volatile anesthetics on the dynamic properties of model membranes. AB - The microscopic mechanism of general anesthesia is still not known but it may be located in the membrane region of nerve cells. In the present article microwave experiments on model membrane systems are discussed. At these particular frequencies a significant decrease of the systems' complex dielectric function is measured when it is exposed to volatile anesthetics. This effect is reversible as well as being identical for chemically quite different anesthetics. The corresponding anesthetic concentrations in the samples are relevant for medical anesthesia. The underlying microscopic mechanism is a decrease in the Debye relaxation frequency (and correspondingly an increase in viscosity) of those water molecules which are localized at the membranes' surfaces. General anesthesia might be a consequence of such a viscosity change at hydrophilic surfaces. PMID- 2223812 TI - An electrophysiological technique to measure change in hepatocyte water volume. AB - We have applied an electrophysiologic technique (Reuss, L. (1985) Proc. Natl. Acad. Sci. USA 82, 6014) to measure changes in steady-state hepatocyte volume during osmotic stress. Hepatocytes in mouse liver slices were loaded with tetramethylammonium ion (TMA+) during transient exposure of cells to nystatin. Intracellular TMA+ activity (alpha 1TMA) was measured with TMA(+)-sensitive, double-barrelled microelectrodes. Loading hepatocytes with TMA+ did not change their membrane potential (Vm), and under steady-state conditions alpha iTMA remained constant over 4 min in a single impalement. Hyperosmotic solutions (50, 100 and 150 mM sucrose added to media) and hyposmotic solutions (sucrose in media reduced by 50 and 100 mM) increased and decreased alpha iTMA, respectively, which demonstrated transmembrane water movements. The slope of the plot of change in steady-state cell water volume, [(alpha iTMA)0/(alpha iTMA)4min] -1, on the relative osmolality of media, (experimental mosmol/control mosmol) -1, was less predicted for a perfect osmometer. Corresponding measurements of Vm showed that its magnitude increased with hyposmolality and decreased with hyperosmolality. When Ba2+ (2 mM) was present during hyposmotic stress of 0.66 X 286 mosmol (control), cell water volume increased by a factor of 1.44 +/- 0.02 compared with that of hyposmotic stress alone, which increased cell water volume by a factor of only 1.12 +/- 0.02, P less than 0.001. Ba2+ also decreased the hyperpolarization of hyposmotic stress from a factor of 1.62 +/- 0.04 to 1.24 +/- 0.09, P less than 0.01. We conclude that hepatocytes partially regulate their steady-state volume during hypo- and hyperosmotic stress. However, volume regulation during hyposmotic stress diminished along with hyperpolarization of Vm in the presence of K(+)-channel blocker, Ba2+. This shows that variation in Vm during osmotic stress provides an intercurrent, electromotive force for hepatocyte volume regulation. PMID- 2223813 TI - Solubility properties of the alkylmethylglucamide surfactants. AB - The critical micelle concentration (CMC) and the ability to solubilize and form vesicles from phospholipids are important criteria for the selection of a surfactant for reconstitution protocols. The CMC and its temperature dependence were determined for an homologous series of alkylmethylglucamides (MEGA-8, MEGA 9, MEGA-10). Each detergent was added continuously from a concentrated solution to a saline buffer with the environment-sensitive fluorescent probe ANS, held in a thermojacketed cuvette; ANS fluorescence increases at the CMC. The CMCs at 25 degrees C were 51.3, 16.0 and 4.8 mM for MEGA-8, MEGA-9 and MEGA-10. The free energy change for transfer to a micellar environment per -CH2- was -740 cal/mol, similar to other alkyl series. The CMCs decreased slightly with increasing temperature (T = 5-40 degrees C) for MEGA-9 and MEGA-10 while that of MEGA-8 was virtually insensitive to temperature in this range. MEGA-9 solubilization of egg PC in aqueous solutions was determined as a function of [PC] and temperature. The lamellar-micellar phase boundaries were determined by simultaneous 90 degrees light scattering and the resonance energy transfer using the headgroup labeled lipid probes NBD-PE and Rho-PE. The [MEGA-9] at solubilization was linear with [PC]; the MEGA-9 to egg PC ratio in the structures at optical clarity was 2.3 while the monomeric [MEGA-9] was 14.3 mM or slightly lower than the CMC at 25 degrees C. Solubilization of egg PC by MEGA-9 was somewhat more temperature dependent than the CMC of this detergent. Vesicles formed from MEGA-9 tended to be multilamellar. MEGA-9 is clearly different from octyl glucoside, despite its chemical similarity, in terms of its temperature sensitivity and vesicle forming characteristics. PMID- 2223814 TI - Uptake of fluorescent plasmalogen analogs by cultured human skin fibroblasts deficient in plasmalogen. AB - One of the consequences of hereditary peroxisomal dysfunction in the cerebro hepato-renal (Zellweger) syndrome (CHRS) is a dramatic decrease in the biosynthesis and cellular content of ether lipids. In the present study effects of reduced cellular plasmalogen levels on membrane-membrane interactions were investigated. Cultured CHRS fibroblasts were incubated with unilamellar phospholipid vesicles consisting of 1-O-alkenyl-2-acyl- or 1,2-diacyl-sn glycerophosphocholines and ethanolamines, carrying either the trans-parinaroyl or the 1,6-diphenyl-1,3,5-hexatriene propionyl group in position 2. Transfer of the fluorogenic phospholipids from vesicles to cells was followed by measuring the concomitant increase in fluorescence intensity. Transfer of phospholipids from cells to vesicles was monitored by incubating cells, prelabeled with [3H]oleic acid, in the presence of phospholipid vesicles. Fibroblasts from healthy donors or CHRS fibroblasts supplemented with the plasmalogen precursor 1-O hexadecylglycerol served as controls. Plasmalogen-deficient cells exhibited a significantly increased tendency to take up exogenous choline or ethanolamine plasmalogens. Cellular plasmalogens were transferred from control cells to vesicles at a higher rate if the acceptor vesicles consisted of plasmalogens as compared to diacylglycerophosphocholine. Thus, it appears as if mechanisms existed which preserve cellular plasmalogen levels during interaction with exogenous phospholipid pools. Preliminary experimental evidence suggests that the observed exchange of phospholipids between cultured fibroblasts and vesicles occurs by a protein-catalyzed process. PMID- 2223815 TI - Influence of 2,3-diphosphoglycerate on the deformability of human erythrocytes. AB - Effect of 2,3-diphosphoglycerate (2,3-DPG) on the deformability of human erythrocytes was examined with a rheoscope under shear stress of 8-82 dyn/cm2. With increasing 2,3-DPG in erythrocytes (from 5 to 15 mM/l cells) by incubating with inosine and pyruvate in isotonic 50 mM phosphate-buffered saline, erythrocyte deformability under uniform shear stress was remarkably impaired. But reduction of 2,3-DPG (from 5 to 2.2 mM/l cells) did not affect the deformability. In 2,3-DPG-enriched erythrocytes, increased intracellular hemoglobin concentration (MCHC), decreased intracellular pH, and increased contents of ATP and IMP (and ITP) were observed. (1) When the MCHC (i.e., the internal viscosity) was normalized by suspending in hypotonic medium, the deformability of 2,3-DPG enriched erythrocytes was greatly improved, but still decreased. (2) The change of intracellular pH between 6.5 and 7.5 (as compared adjusting to same MCHC) did not alter the deformability. (3) The changes of purine nucleotides, ATP (0.6-2.1 mM/l cells), IMP (0-0.9 mM/l cells) and ITP (0-0.5 mM/l cells) did not alter the erythrocyte deformability. In conclusion, decreased deformability of erythrocytes induced by augmentation of 2,3-DPG is due mainly to the increased internal viscosity and due partly to the increased membrane viscoelasticity. PMID- 2223816 TI - Liposomes for the sustained drug release in vivo. AB - New lipidic carriers suitable for the sustained drug release in vivo are presented. They consist of middle sized, compact phospholipid vesicles with one or up to few lipid bilayers which are sterically stabilized with a small amount of large-head phospholipids. As an example, phosphatidylcholine (PC) liposomes casted with up to 10 mol% of phosphatidylethanolamine with a covalently attached polyethyleneglycol 5000 headgroup (PE-PEG) are discussed. Such vesicles exhibit a very long circulation time after an i.v. administration in mice; the improvement over pure phosphatidylcholine liposomes within the first 24 h exceeds 8000%, at this point nearly 25% of the applied PE-PEG liposomes being still in the circulation. This advantage is a consequence of reduced phagocytosis of the lipidic carriers, as shown by an in vitro assay with blood monocyte cells in the flow cytometric experiments. For example, after 6 h incubation with THP-1 monocyte cells in human plasma the difference between the uptake of standard distearoylphosphatidylcholine (DSPC) and novel liposomes containing 10% distearoylphosphatidylethanolamine-PEG is by 1000%. Vesicles with 2.5 mol% DSPE PEG are also taken-up via phagocytosis relatively slowly. But the latter vesicles, moreover, retain most of the enclosed model-drug carboxyfluorescein after an incubation in plasma. The rate of permeation of the encapsulated substance from such DSPE-PEG liposomes is below 2.4% per h. This is by approximately a factor of two less than for pure DSPC liposomes; vesicles with a higher PE-PEG content are inferior in this respect. Long circulation time and high retention of the newly developed liposomes open up ways for the future systemic use as such stabilized drug carriers for the therapeutic applications in vivo. PMID- 2223817 TI - Kinetics and specificity of L-alanine transport across the basolateral cell surface in isolated oxyntic glands. AB - The time course, kinetics, specificity and sodium-dependence of alanine uptake by isolated oxyntic glands were studied. The uptake of alanine by the hydrolyzed cells was measured directly, after incubation of the glands with L-[3H]alanine. L Alanine total influx was saturable and apparently mediated by a single entry system (Kt = 7.93 mM and Vmax = 8.0 mumol.mg-1.30s-1). The Kt was comparable to previously reported values for L-alanine transport in other epithelial cells. Kinetic studies performed in the presence and absence of Na+ suggest L-alanine uptake is mainly mediated by a Na(+)-dependent carrier system, but in addition, a minor diffusional component has been detected. Cross inhibition experiments performed over a wide range of concentrations (1 to 100 mM) suggest that the Na(+)-dependent transport system for alanine resembles system A and displays higher affinity for L-serine (Ki = 1.81 mM) than for L-alanine (K't = 4.86 mM); a lower affinity was found for L-cysteine (Ki = 16.30 mM). Results obtained with MeAIB support the hypothesis that system A is present at the basolateral membrane of the gland cells. PMID- 2223818 TI - Biochemical and molecular aspects of the hepatic uptake of organic anions. PMID- 2223819 TI - Membrane electrostatics. AB - In conclusion, charged membrane together with their adjacent electrolyte solution form a thermodynamic and physico-chemical entity. Their surfaces represent an exceptionally complicated interfacial system owing to intrinsic membrane complexity, as well as to the polarity and often large thickness of the interfacial region. Despite this, charged membranes can be described reasonably accurately within the framework of available theoretical models, provided that the latter are chosen on the basis of suitable criteria, which are briefly discussed in Section A. Interion correlations are likely to be important for the regular and/or rigid, thin membrane-solution interfaces. Lateral distribution of the structural membrane charge is seldom and charge distribution perpendicular to the membranes is nearly always electrostatically important. So is the interfacial hydration, which to a large extent determines the properties of the innermost part of the interfacial region, with a thickness of 2-3 nm. Fine structure of the ion double-layer and the interfacial smearing of the structural membrane charge decrease whilst the surface hydration increases the calculated value of the electrostatic membrane potential relative to the result of common Gouy-Chapman approximation. In some cases these effects partly cancel-out; simple electrostatic models are then fairly accurate. Notwithstanding this, it is at present difficult to draw detailed molecular conclusions from a large part of the published data, mainly owing to the lack of really stringent controls or calibrations. Ion binding to the membrane surface is a complicated process which involves charge-charge as well as charge-solvent interactions. Its efficiency normally increases with the ion valency and with the membrane charge density, but it is also strongly dependent on the physico-chemical and thermodynamic state of the membrane. Except in the case of the stereospecific ion binding to a membrane, the relatively easily accessible phosphate and carboxylic groups on lipids and integral membrane proteins are the main cation binding sites. Anions bind preferentially to the amine groups, even on zwitterionic molecules. Membrane structure is apt to change upon ion binding but not always in the same direction: membranes with bound ions can either expand or become more condensed, depending on the final hydrophilicity (polarity) of the membrane surface. The more polar membranes, as a rule, are less tightly packed and more fluid. Diffusive ion flow across a membrane depends on the transmembrane potential and concentration gradients, but also on the coulombic and hydration potentials at the membrane surface.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2223820 TI - Purification and some properties of cyclodextrin-hydrolyzing enzyme from Bacillus sphaericus. AB - An intracellular cyclodextrin-hydrolyzing enzyme from Bacillus sphaericus E-244 isolated from soil was purified to a homogeneous state by means of Triton X-100 extraction, DEAE-Sepharose column chromatography, hydrophobic and molecular-sieve HPLC. The enzyme was estimated to have an Mr of 72,000 by sodium dodecyl sulfate polyacrylamide gel electrophoresis and 144,000 by HPLC gel filtration on TSK gel G 3000 SW. It had a pH optimum of 8.0, and the enzyme, stable at 25 degrees C and pH 5.5-9.5 for 24 h, was inactivated at 50 degrees C for 10 min. The enzyme hydrolyzed beta-cyclodextrin more effectively than linear maltooligosaccharides such as maltopentaose, maltohexaose and maltoheptaose or polysaccharides such as starch, amylopectin, amylose and pullulan. PMID- 2223821 TI - Biosynthesis of GM1b and similar neolactoseries gangliosides by a partially purified chicken skeletal muscle sialyltransferase. Effect of sphingomyelin and acetylcholine. AB - An alpha 2----3 glycolipid galactosyl sialyltransferase (SAT3/4) has been partially purified from embryonic chicken skeletal muscle. It is preserved in 50 mM Hepes buffer (pH 6.8) containing 1% Triton CF-54 and 20% glycerol at -70 degrees C for a period of 6 months without loss of activity. The SAT3+4 preparation transfers sialic acid to nLcOse4Cer, nLcOse6Cer and GgOse4Cer with respective Km values of 1.4, 0.83 and 0.45 mM. The activity is stimulated 2-3 fold at high substrate concentration and 6-8-fold at low substrate concentration; 0.01 and 0.005 mumol for asialo GM1 and 0.025 and 0.01 mumol for other glycolipids in the presence of phosphatidylcholine (PC) and sphingomyelin (SM) at an optimum concentration 0.75%. A higher concentration is inhibitory. SM from chicken muscle is more effective than that from bovine brain and the stimulation is qualitatively proportional to that of the saturated fatty acyl content of SM. Free fatty acids (palmitic and stearic), their sodium salts, other choline compounds including choline chloride, phosphorylcholine and acetylcholine either do not have any effect or are inhibitory. Acetylcholine, even in the presence of SM and PC, is strongly inhibitory (70%). PMID- 2223822 TI - Induction and regulation of cytochrome P450 K-5 (lauric acid hydroxylase) in rat renal microsomes by starvation. AB - The effects of starvation on rat renal cytochrome P-450s were studied. The content of spectrally measured cytochrome P-450 in the renal microsomes of male rats increased 2-fold with 72 h starvation, but cytochrome b5 and NADPH cytochrome P-450 reductase were not induced. 7-Ethoxycoumarin O-dealkylation and aniline hydroxylation activities of the renal microsomes of control male rats were very low but were induced 2.5-3-fold by 72 h starvation. Aminopyrine N demethylation and lauric acid hydroxylation activities were induced 1.5-2-fold by 72 h starvation. The changes in catalytic activities suggested that the contents of individual cytochrome P-450s in the renal microsomes were altered by starvation. The contents of some cytochrome P-450s were measured by Western blotting. P450 DM (P450IIE1), a typical form of cytochrome P-450 induced by starvation in rat liver, was barely detected in rat kidney and was induced 2-fold by 72 h starvation. P450 K-5, a typical renal cytochrome P-450 and lauric acid hydroxylase, accounted for 81% of the spectrally measured cytochrome P-450 in the renal microsomes of control male rats and was induced 2-fold by 72 h starvation. P450 K-5 was not induced in rat kidney by treatment with chemicals such as acetone or clofibrate. The renal microsomes of male rats contained 6-times as much P450 K-5 as those of female rats. These results suggest that P450 K-5 is regulated by an endocrine factor. PMID- 2223823 TI - The formation of oxalate from glycolate in rat and human liver. AB - In this study, we attempted to elucidate the metabolic pathway and enzymes actually involved in oxalate formation from glycolate in rat and human liver. In rat liver, the formation of oxalate from glycolate appeared to take place predominantly via glyoxylate. The oxalate formation from glycolate observed with crude enzyme preparations was almost entirely accounted for by the sequential actions of glycolate oxidase and xanthine oxidase (XOD) or lactate dehydrogenase (LDH). Under the conditions used, no significant activity was attributable to glycolate dehydrogenase, an enzyme reported to catalyze the direct oxidation of glycolate to oxalate. Among the three enzymes known to catalyze the oxidation of glyoxylate to oxalate, glycolate oxidase and XOD showed much lower activities (a higher Km and lower Vmax) toward glyoxylate than those with the respective primary substrates. As to LDH, none of the LDH subunit-deficient patients examined showed profoundly lowered urinary oxalate excretion. Based on the results obtained, the presumed efficacies in vivo of individual enzymes, as catalysts of glyoxylate oxidation, and the in vivo conditions assumed to allow their catalysis of oxalate production are discussed. PMID- 2223824 TI - Purification and properties of an extracellular conidial trehalase from Humicola grisea var. thermoidea. AB - An extracellular trehalase (alpha, alpha-trehalose glucohydrolase, EC 3.2.1.28) was purified from conidia of Humicola grisea var. thermoidea. The purified enzyme is a glycoprotein and migrates as a single polypeptide band during polyacrylamide gel electrophoresis under non-denaturing conditions. The apparent molecular weight of the enzyme was estimated as 580,000 by gel filtration chromatography. The enzyme is separable into three polypeptide bands of 105,000, 98,000 and 84,000 daltons on SDS-PAGE. It is specific for trehalose and its activity is not inhibited by other disaccharides. It has a Km of 2.3 mM, an optimum pH of 5.6 in sodium acetate buffer and a temperature optimum of 60 degrees C. The enzyme is activated by Ca2+, Co2+ and Mn2+ and inhibited by inorganic phosphate, AMP, ADP or ATP. The inhibitory effect of phosphate, AMP and ADP, but not that of ATP, was abolished in the presence of Ca2+. PMID- 2223825 TI - N-linked oligosaccharides of the murine transferrin receptor from a plasmacytoma cell line. Comparison with total cellular N-glycans. AB - The N-linked oligosaccharides synthesised by the murine plasmacytoma cell line NS 1 have been analysed by lectin affinity chromatography on columns of immobilised concanavalin A (Con A), Lens culinaris (lentil), Ricinus communis agglutinin (RCA) and leuko-phytohemagglutinin (L-PHA). The majority of complex N-glycans in this transformed cell line were branched structures with only a low level of biantennary complex chains detected. The analysis showed the major complex N glycan fraction consisted of a minimum sialylated triantennary structure. [3H]Mannose-labelled transferrin receptor was isolated from NS-1 cells by immunoprecipitation followed by electroelution from SDS polyacrylamide gels. The isolated receptor was digested with Pronase and the 3H-labelled glycopeptides analysed by lectin affinity chromatography. Analysis by Con A-Sepharose indicated that approx. 50% of the labelled glycopeptides were branched complex N-glycans (unbound fraction) while the remainder were oligomannose structures (strongly bound). The presence of tri and/or tetraantennary structures in the Con A unbound fraction was further suggested by the interaction of 61% of the fraction with L PHA. The lectin profiles obtained for the complex N-glycans of the transferrin receptor glycopeptides were similar to those for the total cellular glycopeptides of NS-1 cells. Reverse-phase HPLC analysis of tryptic glycopeptides of the isolated [3H]mannose-labelled transferrin receptor gave three 3H-labelled peaks, indicating that all three potential N-glycosylation sites on the receptor are utilised. The Con A-Sepharose profiles of the three fractions indicated the presence of branched complex N-glycans and high mannose chains at each site. The profiles of two of the tryptic glycopeptide fractions were very similar, while the third had a higher content of oligomannose oligosaccharides. PMID- 2223826 TI - Purification and characterization of an NAD(+)-dependent dehydrogenase that catalyzes the oxidation of thromboxane B2 at C-11 from porcine liver. Development and application of 11-dehydro-thromboxane B2 radioimmunoassay to enzyme assay. AB - 11-Dehydro-thromboxane B2 has been identified as a major metabolite of infused as well as endogenous thromboxane B2 in mammalian plasma and urine. This metabolite is derived from thromboxane B2 by enzymatic oxidation at C-11 catalyzed by 11 hydroxythromboxane B2 dehydrogenase. A radioimmunoassay for 11-dehydro thromboxane B2 has been developed and used for enzyme assay, purification and characterization. Antibodies were generated against 11-dehydro-thromboxane B2 conjugated to bovine thyroglobulin. Labeled marker was prepared by radioiodinating 11-dehydro-thromboxane B2-tyrosine methyl ester conjugate. A sensitive radioimmunoassay capable of detecting 10 pg of 11-dehydro-thromboxane B2 per assay tube was developed. The antibodies showed minimal crossreaction with thromboxane B2 (0.03%), prostaglandin D2 (2.76%) and other eicosanoids (less than 0.03%). The enzyme activity was determined by assaying NAD(+)-dependent formation of immunoreactive 11-dehydro-thromboxane B2 from thromboxane B2. The enzyme was found to be enriched in liver although significant activity was also detected in gastrointestinal tract and kidney in pig. The enzyme was purified from porcine liver cytosol to apparent homogeneity using conventional and affinity chromatography. The purified enzyme exhibited coenzyme specificity for NAD+ and used thromboxane B2 as a substrate. The enzyme also catalyzes NADH-dependent reduction of 11-dehydro-thromboxane B2 to thromboxane B2 indicating the reversibility of the enzyme catalyzed reaction. The apparent Km values for thromboxane B2, 11-dehydro-thromboxane B2 and NAD+ are 8.1, 8.0 and 23 microM, respectively. Subunit Mr was shown to be 55,000, whereas the native enzyme Mr was found to be 110,000 indicating that the enzyme is a dimer. The enzyme is sensitive to sulfhydryl inhibitions suggesting cysteine residues are essential to enzyme activity. The availability of a homogeneous enzyme preparation should allow further studies on the substrate specificity and the structure and function of the enzyme. PMID- 2223827 TI - Differential utilization of long chain fatty acids during fasting-induced triacylglycerol depletion. III. Comparison of n-3 and n-6 fatty acids in rat plasma and liver. AB - Previous research has shown that arachidonic acid (20:4(n-6)) is preferentially retained in liver triacylglycerol in fasted compared to fed rats consuming a diet containing n-6 fatty acids. It was hypothesized that eicosapentaenoic (20:5(n-3)) and docosahexaneoic acids (22:6(n-3)) would be similarly retained in liver and plasma triacylglycerol of fasted rats consuming a diet containing n-3 fatty acids. In comparison with fed rats, it was observed that in partially fasted rats consuming diets which contained 5% sunflower oil (78% 18:2(n-6)) or 5% marine fish oil (30% 20:5(n-3) and 22:6(n-3)), both liver and plasma had significantly depleted triacylglycerol levels containing higher proportions of both arachidonic and docosahexaneoic acids but a lower proportion of eicosapentaenoic acid (marine fish oil group only). Separation of liver and plasma triacylglycerol by silicic acid column chromatography and silver nitrate TLC showed that the majority of long chain fatty acids utilized during fasting were derived from the triacylglycerol subclasses containing palmitic acid (16:0), palmitoleic acid (16:1(n-7)) and oleic acid (18:1(n-9)) with retention o both highly saturated and polyunsaturated subclasses. Greater utilization of eicosapentaenoic acid than either arachidonic acid or docosahexaenoic acid during fasting may be due to triacylglycerol speciation of the former with readily oxidized monounsaturated fatty acids. PMID- 2223828 TI - An EXAFS, and preliminary X-ray crystallographic, investigation of an iron containing product from the lichen Cladonia deformis. AB - An iron-containing product in the acetone extract from the lichen Cladonia deformis has been investigated using chemical, spectroscopic and X-ray crystallographic methods. Visible-near UV, EPR and IR spectra indicate that the iron is present as high-spin Fe(III) and coordinates in an oxygen-containing environment arising from graciliformin (or graciliformin-like) ligands. This has been confirmed by an XAS (X-ray absorption) study using synchrotron radiation. Comparison of the EXAFS and XANES results with those obtained from a model, tris(pent-2,4-dionato)Fe(III), and detailed fitting using the single-scattering, curved-wave formalism for the EXAFS strongly supports the presence of a Fe(III) coordinated to five oxygen atoms from the graciliformin. PMID- 2223829 TI - Is adenosine a second metabolic substrate for human red blood cells? AB - Adenosine is present in the micromolar range in human plasma. In this study, metabolism of adenosine, which was maintained between 0.62 +/- 0.03 and 2.92 +/- 0.43 microM by means of a continuous infusion using a Harvard infusion pump, was investigated in human red blood cells. It was found that lactate production increases linearly as the adenosine concentration was raised. Cells infused with an average adenosine concentration of 2 microM produced lactate comparable to that produced by 5 mM glucose. The extent to which ATP concentration is maintained by adenosine also depends on its concentration. After a 4 h infusion with an average adenosine concentration of 0.7 microM, ATP content amounts to 75% of the glucose control. Raising the adenosine infusion concentration to 1.5 microM results in a full maintenance of ATP levels and at concentrations higher than 1.5 microM, adenosine produces a net synthesis of ATP. A net synthesis of ATP also occurs with adenosine concentration below 1.5 microM, if supplemented with glucose. In contrast, inosine infusion provides only a partial support of ATP and fails to produce a net synthesis of ATP in the presence of glucose. In addition, the presence of purine nucleoside and glucose together influence the metabolism of each other, depending on inorganic phosphate content (Pi). At a Pi concentration of 1 mM, the glucose consumption rate is reduced by approx. 25% by purine nucleoside infusion and vice versa. In sharp contrast, glucose consumption at 16 mM Pi is potentiated by adenosine. These findings suggest that plasma adenosine contributes significantly to human red cell energetics, even though it is present at a concentration several orders of magnitude lower than glucose. PMID- 2223830 TI - Comparison of the binding of anthracycline derivatives to purified DNA and to cell nuclei. AB - Fluorescence method was used to study the interactions of anthracyclines with purified DNA and with cell nuclei at 37 degrees C, at pH ranging from 6.8 to 8. Four anthracyclines were used; adriamycin (ADR), 4'-o-tetrahydropyranyladriamycin (THP-ADR), daunorubicin (DNR) and aclacinomycin (ACM). The values of pKa of deprotonation of these four drugs in the pH range 6.5-8.5 are 8.4, 7.7, 8.4 and 7.0 for ADR, THP-ADR, DNR and ACM, respectively. The overall binding constants K* of these four drugs to purified DNA was determined at various pH values. The binding constants K0 and K+ of the respectively neutral form and once protonated form of the drugs to DNA were calculated. Using cell nuclei from K562 cells, the amount of drug intercalated (CN) within the nuclei of K562 cells and the amount of free drug (CE) in the solution were determined at various pH values: measuring at the same pH values, a linear correlation occurred between K* and CN/CE. PMID- 2223831 TI - Identification of non-equilibrium glycolytic reactions in suspension-cultured plant cells. AB - Levels of all enzymes and metabolites involved in glycolysis were determined in suspension-cultured Catharanthus roseus cells. From both the maximum catalytic activities of the enzymes and comparisons of mass-action ratios with the apparent equilibrium constants for the reactions, it is concluded that the reactions catalysed by hexokinase, fructokinase, phosphofructokinase and pyruvate kinase are far from equilibrium, whereas the other reactions including that catalysed by pyrophosphate-fructose-6-phosphate 1-phosphotransferase, are close to equilibrium in vivo. PMID- 2223832 TI - Characterization of ent-kaurene oxidase activity from Gibberella fujikuroi. AB - Cell extracts of wild-type and mutant strains of Gibberella fujikuroi were assayed for kaurene oxidase activity, using ent-[3H]kaurene as the substrate. Extracts from strain SG78 exhibited the highest specific activity, and were used in subsequent experiments. The microsomal enzyme activity was solubilized with buffers or salt solutions at a concentration of 400 mM. Both the soluble and microsomal preparations showed characteristic cytochrome P-450 spectra, ligand binding spectra with the substrate and with the plant growth regulator, paclobutrazol, and inhibition of enzymic activity by carbon monoxide. The addition of 20% glycerol to the extraction buffer stabilized the activity to some extent. Loss of enzymic activity on storage was accompanied by conversion of P 450 to P-420. Michaelis-Menten kinetic parameters for the membrane-bound and soluble enzyme have been estimated, as have constants for the binding of ent kaurene and paclobutrazol to the P-450 and P-420 forms of the protein. PMID- 2223833 TI - Histamine tautomerism and its mode of action. AB - An established combination of quantum mechanical calculations and molecular dynamics simulations (Worth, C.A., King, P.M. and Richards, W.G. (1989) Biochim. Biophys. Acta 993, 134-136; Cieplak, P., Singh, U.C. and Kollman, P.A. (1987) Int. J. Quant. Chem. QBS14, 65-74; Reynolds, C.A., King, P.M. and Richards, W.G. (1988) Nature 334, 80-82) has been used to calculate the tautomer ratios of histamine species in aqueous solution. The results are in good agreement with experiment and provide a bridge between experimental data and earlier theoretical calculations. PMID- 2223834 TI - Isolation and characterization of a new lectin from plasma of fish Channa punctatus. AB - A soluble lectin is purified to apparent homogeneity from plasma of Channa punctatus by affinity chromatography on N-acetyl-D-galactosamine coupled to epoxy activated cellulose. The lectin has 140 kDa native molecular mass and 68 kDa subunit molecular mass, as determined by native and sodium dodecyl sulphate denaturing polyacrylamide gel electrophoresis, respectively. The lectin agglutinates human A and AB blood groups and rat, mice and guinea pig erythrocytes in the presence of Ca2+ and Mg2+ or Mn2+ ions. These divalent cations, but not thiol group, are obligatory requirements for the lectin activity. Gal(beta 1----3)GalNAc (0.09 mM) is the most potent inhibitor of the lectin. PMID- 2223835 TI - Phospholipid hydroperoxide glutathione peroxidase in various mouse organs during selenium deficiency and repletion. AB - An assay for the determination of the newly discovered selenoenzyme, phospholipid hydroperoxide glutathione peroxidase (PH-GPx) in biological material is described. Dietary selenium deficiency and repletion was used as a tool in order to modify this enzyme activity in various mouse organs and to compare it to the activity of the 'classical' selenium-dependent glutathione peroxidase (GPx) (EC 1.11.1.9). A semipurified diet containing less than 12 ppb Se was used for depletion. Controls received this diet supplemented with 500 ppb Se in the form of Na2SeO3. The results showed that a rapid loss of GPx activity occurred in liver, kidney and lungs of selenium-deficient mice which reached undetectable levels within 130 days. In the heart, about 24% of control GPx activity was still present. In contrast, PH-GPx activity was more slowly depleted by Se deficiency and resulted in residual activities ranging from 30 to 70% in the different organs even after 250 days of depletion. In repletion experiments with a single application of 10 or 500 micrograms/kg Se, only the high dose restored either enzyme activity. The data demonstrate that the need for selenium of the two glutathione peroxidases is different. A markedly distinct organ distribution of both enzymes suggests that the heart may be the organ more sensitive to oxidative stress. PMID- 2223836 TI - A physicochemical comparison of the isozymes of creatine kinase from rabbit brain and muscle. AB - A comparison of specific structural features of creatine kinase from rabbit muscle and brain was undertaken to determine if the observed isozyme specific differences in catalytic cooperativity are related to conformational differences, particularly differences in packing density. The intrinsic fluorescence of the brain isozyme is 2-fold higher than the muscle isozyme. In the denatured state, both proteins display the characteristic red shift in emission maximum; however, the emission intensity of the brain isozyme increases only 5% upon denaturation compared to nearly 100% increase for the muscle protein. The fluorescence lifetimes are 2.65 ns (67%) and 0.48 ns for native muscle enzyme and 4.38 ns (65%) and 0.80 ns for brain enzyme. Upon denaturation, the lifetimes are 3.98 ns (77%) and 0.99 ns for muscle protein and 3.82 ns (79%) and 0.86 ns for brain protein. Stern-Volmer plots of quenching by acrylamide are essentially the same for both native isozymes indicating that the differences of the intrinsic fluorescence of the native proteins are not due to differences in solvent accessibility. The spectral and lifetime differences in the isozymes in the native state and changes accompanying denaturation are consistent with the occurrence of energy transfer in native muscle isozyme. The rotational correlation times of 5-[2-(iodoacetyl)aminoethyl]aminonaphthalene-1-sulfonate conjugated proteins, derivatized at the active site reactive thiol, are best described by two term decay laws. The slower rotations, 45.1 ns (75%) and 40.6 ns (71%) reflect overall macromolecular rotation for the muscle and brain isozymes, respectively. The faster motions, 2.4 ns for muscle isozyme and 0.4 ns for the brain isozyme, are attributed to the probe or probe associated segmental motions and indicate these motions are more restricted in the muscle protein. Reactivity of creatine kinase (2.5-10 microM) with the amino-specific reagent trinitrobenzene sulfonate (0.4-2 mM) was analyzed by pseudo-first-order and second order models, neither of which was adequate for the entire range of data. However, in every case, the rate constants were faster for brain creatine kinase but the extent of reaction was greater for muscle creatine kinase. The faster initial reactivity of the brain isozyme is consistent with greater accessibility for lysine derivatization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2223837 TI - A Fourier transform infrared spectroscopic (FTIR) study of porcine and bovine pancreatic phospholipase A2 and their interaction with substrate analogues and a transition-state inhibitor. AB - Fourier transform infrared spectroscopy has been used to investigate the secondary structure of porcine and bovine pancreatic phospholipase A2 (PLA2) and the zymogen of porcine PLA2, prophospholipase A2 (proPLA2), in both H2O and D2O media. Detailed qualitative analysis was made of these proteins using second derivative and deconvolution techniques. Quantitative studies of the proteins in solution made using Factor Analysis gave average values of 54% alpha-helix, 15% beta-sheet and 23% beta-turns. These values agree well with the secondary structures deduced from previous studies of single crystals using X-ray techniques. No significant differences in secondary structure were observed for porcine pancreatic (pro)phospholipase A2 in the presence or absence of Ca2+ ions, or in the temperature range 10-45 degrees C. The binding of the non-degradable phospholipid analogue, n-alkylphosphocholine, in monomeric form produced no significant difference in the secondary structure of either enzyme. Conformational differences were, however, observed between the enzyme lyophilised in a solid film and in aqueous solution. The change is probably due to the formation of beta-sheet upon hydration, coupled with a loss of random structures. Conformational differences in both porcine and bovine pancreatic PLA2 were observed on binding to n-alkylphosphocholine micelles. This change may be due to a small increase in the alpha-helical structure and a decrease in the beta-sheet, and/or possibly beta-turn content. Similar conformational changes were observed for the interaction of porcine and bovine PLA2 with the substrate analogue inhibitor 1-heptanoyl-2-heptanoylamino-2-deoxy-sn-glycero-3-phospho glycol in micellar form. PMID- 2223838 TI - Functional modification of an arginine residue on salicylate hydroxylase. AB - Salicylate hydroxylase from Pseudomonas putida (EC 1.14.13.1, salicylate, NADH:oxygen oxidoreductase) is an FAD-containing monooxygenase, which catalyzes decarboxylative hydroxylation of salicylate to produce catechol in the presence of NADH and O2. By chemical treatment of the enzyme with dicarbonyl reagents, such as glyoxal, the original oxygenase activity was converted to the salicylate dependent NADH-dehydrogenase activity with free FAD as electron acceptor. One of twenty arginine residues of this enzyme is concerned with this alteration of activity, as shown by the result of its modification at pH 6.9. This result is further supported by the isolation of one arginine-modified enzyme by chromatographic methods on DEAE-Sephadex, A-50 columns. It exhibits the dehydrogenase activity predominantly. This modified enzyme is spectrophotometrically and electrophoretically characterized by a minute conformational change around the active site, and kinetically by a 7-fold increase in an apparent Km for NADH and a decrease of more than 5-fold in an apparent Km for FAD as electron acceptor, with an apparent Vmax of 22 s-1 for the dehydrogenase activity. Flow kinetics also showed a marked decrease in the rate for oxygenation of the reduced enzyme-salicylate complex from 21 s-1 (native enzyme) to 3.3 s-1 (modified enzyme). These facts suggest that one arginine residue of the enzyme is responsible for the NADH binding site, and chemical modification of one arginine residue of the enzyme induces some conformational change around the active site to alter the catalytic activity from oxygenation to dehydrogenation. PMID- 2223839 TI - Fluorescence-quenching-resolved spectra of melittin in lipid bilayers. AB - The interaction of bee venom melittin with dimyristoylphosphatidylcholine (DMPC) unilamellar vesicles has been studied by means of fluorescence quenching of the single tryptophan residue of the protein, at lipid-to-peptide ratio, Ri = 50 and at high ionic strength (2 M NaCl). The method of fluorescence-quenching-resolved spectra (FQRS), applied in this study with potassium iodide as a quencher, enabled us to decompose the tryptophan emission spectrum of liposome-bound melittin into components, at temperatures above as well as below the main phase transition temperature (Tt) of DMPC. One of the two resolved spectra exhibits maximum at 342 and 338 nm for experiments above and below Tt, respectively, and is similar to the maximum of tryptophan emission found for tetrameric melittin in solution (340 nm). This spectrum is characterized by the Stern-Volmer quenching constant, Ksv, of about 4 M-1 and it represents the fraction of melittin molecules whose tryptophan residues are exposed to the solvent to a degree comparable with tetrameric species in solution. The other spectrum component, corresponding to the quencher-inaccessible fraction of tryptophan molecules (Ksv = 0 M-1) has its maximum blue-shifted up to 15 nm, indicating a decrease in polarity of the environment. For experiments above Tt, the blue spectrum component revealed the excitation-wavelength dependence, originating probably from the relaxation processes between the excited tryptophan molecules and lipid polar head groups. We conclude that melittin bound to DMPC liposomes exists in two lipid-associated forms; one, with tryptophan residues exposed to the solvent and the other, penetrating the membrane interior, with tryptophan residues located in close proximity to the phospholipid polar head groups of the outer vesicle lipid layer. We also discuss our data with current models of melittin bilayer interactions. PMID- 2223840 TI - Thermodynamic properties of globular proteins and the principle of stabilization of their native structure. AB - A semi-empirical method has been used to estimate the thermodynamic parameters of hydration of buried surface areas of ribonuclease S, lysozyme and myoglobin from the model of complete unfolding according to Ooi et al. ((1987) Proc. Natl. Acad. Sci. USA 84, 3086-3090). The buried surface area of proteins is considered as the difference between the accessible surface area of native protein and the completely extended polypeptide chain according to Lee and Richards ((1971) J. Mol. Biol. 55, 379-400). The contributions of nonpolar and polar protein groups to the general value of Gibbs energy, enthalpy, entropy and heat capacity of hydration have been determined. The obtained results on the thermodynamic behavior of proteins in the process of complete unfolding are in good agreement with the results of microcalorimetric studies of thermal denaturation. PMID- 2223841 TI - Interaction of human leukocyte elastase with soluble and insoluble protein substrates. A practical kinetic approach. AB - A progress-curve kinetic method was developed to investigate the interaction between human leukocyte elastase and macromolecular substrates, such as insoluble elastin and soluble plasma proteins. A fluorogenic, synthetic peptide (reporter substrate) was incubated in the presence of finely powdered elastin and enzyme under continuous stirring. The progress curves, which corresponded to the release of product from the reporter substrate, were very sensitive to the presence of various amounts of the macromolecular substrate. The kinetic parameters for the interaction between elastase and elastin were calculated using a pre-steady-state approach characteristic of slow-binding inhibitors. The interaction of elastase with the soluble protein substrates was studied with similar techniques, but formally treating the substrates as classical, fully competitive inhibitors. The adsorption of elastase on insoluble elastin was a time-dependent process consisting of at least three observable phases: The first step was a rapid formation of an encounter complex followed by a very slow step lasting several minutes, and the third step consisted of a steady-state release of products. On the contrary, elastase very rapidly formed productive complexes with bovine serum albumin and a human monoclonal immunoglobulin G. The progress-curve method was also suitable for analyzing the behavior of inhibitors in the presence of protein substrates. The kinetic parameters which characterize the interaction between elastase and protein substrates represent a practical tool to formulate hypotheses on the efficiency of inhibitors in vivo. PMID- 2223842 TI - Hydrostatic pressure studies of native and synthetic thick filaments: II. Native thick filaments from rabbit skeletal muscle. AB - Native thick filaments isolated from freshly prepared rabbit psoas muscle were found to be resistant to pressure-induced dissociation. With increasing pressure application and release, a bimodal distribution of filament lengths was observed. The shorter filament length is associated with filament breakage at the center of the bare zone, while the longer length is associated with relatively intact filaments. Intact filaments and filament halves decrease in length by no more than 20% after exposure to and release of 14,000 psi. Bimodal distributions were not observed in equivalent experiments performed on filaments isolated from muscle glycerinated and stored at -20 degrees C for 6 months. Instead, filament dissociation proceeds linearly as a function of increasing pressure. Filaments prepared from muscle glycerinated and stored for 2 and 4 months exhibited pressure-induced behavior intermediate between the filaments prepared from fresh muscle and filaments prepared from muscle stored for 6 months. Since there appears to be no difference in the protein profiles of the various muscle samples, it is possible that stabilization of the native thick filament against hydrostatic pressure arises from trapped ions that are leached out over time. PMID- 2223843 TI - The histone H1 globular region. A possible supersecondary structure from spectroscopic and statistical studies. AB - The central region of the basic nuclear protein, histone H1, has a highly conserved amino acid sequence and a globular structure which is still not known at atomic resolution. A possible secondary and supersecondary structure was predicted by combining experimental measurements of circular dichroism and NMR spectroscopy with a statistical method based on the amino acid sequence. Our results showed the protein fragment as being highly structured and having a total alpha-helix content of about 40%. PMID- 2223844 TI - Primary sequence of duck metallothionein. AB - Only one metallothionein appears in domesticated duck upon zinc induction. The complete amino acid sequence has been elucidated. This metallothionein has the same sequence as the chicken metallothionein, as determined by chemical sequencing of overlapping peptides produced by selective proteinase digestion and confirmed by mass spectrometry. The observation that animals of divergent origins share a common gene product presents an example of extreme conservation of a stress-inducible protein. PMID- 2223845 TI - Chloroplast glyceraldehyde-3-phosphate dehydrogenase (NADP): amino acid sequence of the subunits from isoenzyme I and structural relationship with isoenzyme II. AB - The structural relationship between isoenzymes I and II of chloroplast glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate: NADP+ oxidoreductase (phosphorylating) EC 1.2.1.13) has been established at the protein level. The complete primary structure of subunits A and B of glyceraldehyde-3 phosphate dehydrogenase I from Spinacia oleracea has been determined by sequence analysis of the corresponding tryptic peptides, aligned by fragments derived from cyanogen bromide and Staphylococcus proteinase V8 digestions and by partially sequencing each intact subunit. Subunit A has an Mr of 36,225 and consists of 337 amino acid residues, whilst subunit B (Mr 39,355) consists of 368 residues. The amino acid sequence of subunit B, as determined through direct analysis of the protein, is identical to that recently deduced at cDNA level (Brinkmann et al. (1989) Plant Mol. Biol. 13, 81-94). The two subunits share a common portion of amino acid sequence which differs by 66 amino acid residues. Subunit B has an extra C-terminal sequence of 31 amino acid residues. Chloroplast glyceraldehyde-3 phosphate dehydrogenase II was partially characterized by sequencing the N terminal portion of the intact protein and some of its tryptic peptides. The sequences of all the examined fragments fit precisely that of the corresponding regions of subunit A from glyceraldehyde-3-phosphate dehydrogenase I. PMID- 2223846 TI - A kinetic study on the suicide inactivation of peroxidase by hydrogen peroxide. AB - In the absence of reductant substrates, and with excess H2O2, peroxidase (donor: hydrogen-peroxide oxidoreductase, EC 1.11.1.7) shows the kinetic behaviour of a suicide inactivation, H2O2 being the suicide substrate. From the complex (compound I-H2O2), a competition is established between two catalytic pathways (the catalase pathway and the compound III-forming pathway), and the suicide inactivation pathway (formation of inactive enzyme). A kinetic analysis of this system allows us to obtain a value for the inactivation constant, ki = (3.92 +/- 0.06) x 10(-3) x s-1. Two partition ratios (r), defined as the number of turnovers given by one mol of enzyme before its inactivation, can be calculated: (a) one for the catalase pathway, rc = 449 +/- 47; (b) the other for the compound III-forming pathway, rCoIII = 2.00 +/- 0.07. Thus, the catalase activity of the enzyme and, also, the protective role of compound III against an H2O2-dependent peroxidase inactivation are both shown to be important. PMID- 2223848 TI - Proteolytic activity in mouse urine: relationship to the kidney metallo endopeptidase, meprin. AB - Meprin, a brush border kidney metallo-endopeptidase is present as the major endopeptidase in mouse urine. The enzyme is freely soluble and can be detected enzymically or immunologically. Mice can be partitioned into two phenotypes that differ by 10-20-fold in the amount of meprin in kidney membranes; this phenotypic variation is reflected in urinary activities. We propose a role for meprin in the degradation of other urinary proteins. PMID- 2223847 TI - Conditions affecting the activity of glucocerebrosidase purified from spleens of control subjects and patients with type 1 Gaucher disease. AB - Glucocerebrosidase was purified to homogeneity from spleens of control subjects and Type 1 Gaucher disease patients by immunoaffinity chromatography. Activation of the enzyme by taurocholate, phosphatidylserine and sphingolipid activator protein 2 (saposin C; SAP-2) was investigated by titration of combinations of various effectors in the absence and presence of Triton X-100. The specific activity of Type 1 Gaucher glucocerebrosidase was found to be less than 20% of the corresponding control value under most conditions. However, in the presence of optimal amounts of activator protein SAP-2 and phosphatidylserine (and in the absence of Triton X-100 and/or taurocholate), the specific activity of mutant enzyme towards artificial and natural lipid substrates was close to normal when measured at pH 5.0-5.5. At pH values below 5.0, the specific activity of mutant enzyme decreased more rapidly compared to that of control enzyme. The activity of Type 1 Gaucher glucocerebrosidase in the intact cell might, in a comparable manner, be highly dependent on the extent of activation by endogenous activators and on the intralysosomal pH. Values for residual glucocerebrosidase activity, as measured in vitro in extracts of cells and tissues from Type 1 Gaucher disease patients, are indeed highly dependent on the assay conditions employed. Consequently such measurements are of little value in the assessment of the actual capacity for glucosylceramide hydrolysis and for prediction of the clinical severity of the disease. PMID- 2223849 TI - Increased nucleophile reactivity of amino acid beta-naphthylamides in alpha chymotrypsin-catalyzed peptide synthesis. AB - Alpha-chymotrypsin-catalyzed acyl transfer from Boc-L-MetONp, Ac-L-TyrOEt, Bz-L TyrOMe, Mal-L-PheOMe to the C-protected amino acids (L-AlaNH2, L-LeuNH2, L-ArgOMe and beta-naphthylamides of L-Arg, L-Leu, L-Ala and L-Glu) has been studied. Modification of the carboxylic groups with beta-naphthylamide was shown to increase the reactivity of nucleophiles in these reactions by a factor of more than 100 in comparison with amides and esters of the same amino acids. This effect can be accounted for by the effective formation of the nucleophile acylenzyme complex due to hydrophobic interactions of the beta-naphthylamide moiety with the corresponding subsite of alpha-chymotrypsin. The reaction kinetics follows the scheme involving hydrolysis of the nucleophile-acylenzyme intermediate. The contribution of this pathway depends on the structures of both the acyl-group donor and the added nucleophile. The competitive inhibition by amino acid beta-naphthylamides is also observed. The results obtained show that modification of the COOH-group of added nucleophiles by beta-naphthylamide strongly affects the reactivity of these compounds in the alpha-chymotrypsin catalyzed peptide synthesis. PMID- 2223850 TI - Dimensional mapping of the active site of cholesterol esterase with alkylboronic acid inhibitors. AB - The cholesterol esterase-catalyzed hydrolysis of the water-soluble substrate p nitrophenyl butyrate occurs via an acylenzyme mechanism, and is competitively inhibited by boronic acid transition state analog inhibitors. Accordingly, we undertook to dimensionally map the enzyme's active site via synthesis and characterization of a series of n-alkyl boronic acid inhibitors. The most potent of these is n-hexaneboronic acid, with a Ki = 13 +/- 1 microM, since inhibitor potency declines for both longer and shorter boronic acids. No inhibition is observed for methaneboronic acid and n-octaneboronic acid inhibits poorly, with a Ki of 7 mM. These results indicate that the ability of the enzyme to form tight complexes with boron-containing transition state analog inhibitors is sensitive to alkyl chain length. The trend in inhibitor potency is discussed in terms of substrate specificity of and transition state stabilization by cholesterol esterase, and has important implications for the design of optimal reversible inhibitors of the enzyme. PMID- 2223851 TI - Interaction of aromatic donor molecules with manganese(III) reconstituted horseradish peroxidase: proton nuclear magnetic resonance and optical difference spectroscopic studies. AB - The interaction of aromatic donor molecules with manganese(III) protoporphyrin apohorseradish peroxidase complex [Mn(III)HRP] was investigated by optical difference spectroscopy and relaxation rate measurements of 1H resonances of aromatic donor molecules (at 500 MHz). pH dependence of substrate proton resonance line-widths indicated that the binding was facilitated by protonation of an amino acid residue (with a pKa of 6.1), which is presumably distal histidine. Dissociation constants were evaluated from both optical difference spectroscopy and 1H-NMR relaxation measurements (pH 6.1). The dissociation constants of aromatic donor molecules were not affected by the presence of excess of I-, CN- and SCN-. From competitive binding studies it was shown that all these aromatic donor molecules bind to Mn(III)HRP at the same site, which is different from the binding site of I-, CN- and SCN-. Comparison of the dissociation constants between the different substrates suggests that hydrogen bonding of the donors with distal histidyl amino acid and hydrophobic interaction between the donors and active site contribute significantly towards the associating forces. Free energy, entropy and enthalpy changes associated with the Mn(III)HRP substrate equilibrium have been evaluated. These thermodynamic parameters were found to be all negative. Distances of the substrate protons from the paramagnetic manganese ion of Mn(III)HRP were found to be in the range of 7.7 to 9.4 A. The Kd values, the thermodynamic parameters and the distances of the bound aromatic donor protons from metal center in the case of Mn(III)HRP were found to be very similar as in the case of native Fe(III)HRP. PMID- 2223852 TI - Acyl carrier protein interacts with melittin. AB - Acyl carrier protein (ACP) from Escherichia coli has been shown to form complexes with melittin, a cationic peptide from bee venom. ACP is a small (Mr 8847), acidic, Ca2(+)-binding protein, which possesses some characteristics resembling those of regulatory Ca2(+)-binding proteins including interaction with melittin. Complexing between melittin and ACP which occurred both in the presence and absence of Ca2+ was evident by chemical cross-linking the two peptides, fluorescence changes (including anisotropy measurements), and inhibition by melittin of the activity of a nonaggregated fatty acid synthetase from Euglena. Also, anti-Apis mellifera antibodies which contained antibodies against melittin specifically inhibited the same enzyme system activity relative to non-immune IgG. PMID- 2223853 TI - Polar lipids of non-alkaliphilic Halococci. AB - Until recently, only one species of Halococcus has been recognized, namely, H. morrhuae, but a large number of extremely halophilic non-alkaliphilic cocci have now been isolated from hypersaline habitats in Spain and classified into four phenons (A-D); one of the phenon D strains has been classified as a new species, Halococcus saccharolyticus. Examination of the lipids of H. saccharolyticus and four strains of phenons A-C showed the presence in all of them of C20-C20 and C20 C25 diether molecular species of phosphatidylglycerophosphate (PGP), phosphatidylglycerol (PG) and phosphatidic acid (PA); a monounsaturated isoprenoid C20-C20 (phytanyl-phytenyl) species of PGP; a sulfated diglycosyl diphytanylglycerol (S-DGD) with structure 2,3-diphytanyl-1-(6-HSO3-mannosyl-1-2 glucosyl)-glycerol, which is identical to the S-DGD-1 in Haloferax mediterranei; a phosphoglycolipid (P-TGD) tentatively identified as a phytanyl-phytenyl-(H2PO3 galactosyl-mannosyl-glycosyl)-glyce rol, and two unidentified glycolipids present only in traces. No phosphatidylglycerosulfate (PGS) was detected in any of the strains examined. This pattern of lipids appears to be characteristic of the strains of Halococcus from salterns in Spain, but studies of a larger number and variety of Haloccus are necessary to establish this conclusion with certainty. PMID- 2223854 TI - Influence of polyunsaturated and saturated dietary lipids on adipose tissue, brain and mitochondrial membrane fatty acid composition of a mammalian hibernator. AB - Dietary lipid composition profoundly influences the hibernation pattern of the chipmunk Eutamias amoenus. The object of the present study was to investigate whether these physiological changes following feeding of saturated and unsaturated lipids were associated by compositional changes of fatty acids of tissues and membranes. Animals were fed with rodent chow (control diet), rodent chow with 10% sunflower seed oil (unsaturated diet) and rodent chow with 10% sheep fat (saturated diet). Diet-induced changes in the fatty acid composition of depot fat and brain total lipids and of mitochondrial phospholipids were determined. The fatty acid unsaturation index was lower in animals on saturated diet than in animals on unsaturated diet (depot fat 86.1 vs. 145.9; heart mitochondria 207.6 vs. 247.1; liver mitochondria 148.4 vs. 173.5). Pronounced differences between dietary groups were also observed in n-3 or n-6 fatty acids or their ratios of depot fat, brain and liver mitochondria. Generally, the diet induced differences in tissue and membrane fatty acid composition in E. amoenus were more pronounced than those observed previously in non-hibernating species. Selective feeding and incorporation of high amounts of unsaturated fatty acids into tissues and cell membranes may be an important preparation for hibernation of E. amoenus which lowers its body temperature during torpor to about 0 degrees C. PMID- 2223855 TI - Metabolism of 13-hydroxy-9,11-octadecadienoic acid by MOLT-4 lymphocytes. AB - MOLT-4 lymphocytes metabolize 13-hydroxy-9,11-octadecadienoic acid, via the beta oxidation pathway with retention of the omega 6 hydroxyl group and the conjugated diene system. The products which accumulate include 11-hydroxy-7,9 hexadecadienoic acid and 9-hydroxy-5,7-tetradecadienoic acid. In addition, it was possible to isolate two beta-hydroxy acids which were shown to be 3,13-dihydroxy 9,11-octadecadienoic acid and 3,11-dihydroxy-7,9-hexadecadienoic acid. The odd chain aldehyde, 12-hydroxy-8,10-heptadecadien-1-al, also was detected. However, neither the pathway nor the immediate precursor for the synthesis of this compound was established. PMID- 2223856 TI - Differential induction of peroxisomal oxidation of palmitic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid in rat liver. AB - The effect of feeding rats 20% partially hydrogenated marine oil (PHMO), 20% soybean oil, or clofibrate on the conversion of 3 alpha,7 alpha,12 alpha trihydroxy-5 beta-cholestanoic acid to cholic acid was studied in light mitochondrial (L) fractions prepared from liver. 20% PHMO gave a doubling both of the specific and of the total activity of the cholic acid formation compared to those found in the L-fraction from animals given standard pellets. 20% soybean oil induced the specific and the total activity to a lesser extent, 1.4- and 1.2 fold, respectively. The specific and total activity of the peroxisomal beta oxidation of palmitic acid were induced 2.4- and 2.7-fold, respectively, by PHMO feeding. Soybean oil gave a smaller increase, 2-fold, in both specific and total activity. Clofibrate, a known peroxisomal proliferator, induced the specific and total activity of the peroxisomal fatty acid beta-oxidation 5.2- and 5.7-fold, respectively, whereas the specific activity of the cholic acid formation remained unchanged compared to standard pellet feeding. The same pattern was found in the postnuclear supernatants (E-fractions), excluding the possibility that different treatments caused different distributions of organelles between the fractions. This differential induction of two similar peroxisomal reaction sequences suggests that at least two mechanisms for peroxisomal induction exist. PMID- 2223858 TI - Purification and characterization of phospholipase A2 from rat stomach. AB - Phospholipase A2, which is localized in the mucosal part of the corpus of rat stomach (Hirohara et al. (1987) Biochim. Biophys. Acta 919, 231-238), was purified 990-fold from the supernatant of a tissue homogenate by heat treatment at acidic pH, ammonium sulfate fractionation, ion-exchange chromatography, gel filtration and reverse-phase high-performance liquid chromatography (reverse phase HPLC). The purified enzyme gave a single protein band on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis with a molecular mass of approx. 17 kDa. The enzyme had a pH optimum of 8.0 and hydrolyzed the 2-arachidonoyl residue of phosphatidylcholine preferentially to the 2-oleoyl residue, the Vmax and Km values for the two being 227 and 29 mumol/min per mg protein and 0.037 and 0.019 mM, respectively. The activity was calcium-dependent and was markedly increased by SDS and dimethyl sulfoxide (DMSO). The enzyme showed typical product inhibition. Free unsaturated fatty acids (oleic, arachidonic and docosahexaenoic acids), which are supposedly the main enzymatic products in vivo, inhibited the activity. Arachidonic acid caused noncompetitive inhibition and its concentration for its maximal inhibition (50% inhibition) was 5 x 10(-5) M. Lysophosphatidylcholine, free saturated fatty acids (palmitic and stearic acids) and arachidonic acid metabolites (leukotrienes and prostaglandins) had no effect on the activity. PMID- 2223857 TI - Hydrolysis of lipid mixtures by rat hepatic lipase. AB - The hydrolysis of phospholipid mixtures by purified rat hepatic lipase, also known as hepatic triglyceride lipase, was studied in a Triton X-100/lipid mixed micellar system. Column chromatography of the mixed micelles showed elution of Triton X-100 and binary lipid mixtures of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine as a single peak. This indicated that the mixed micelles were homogenous and contained all components in the designated molar ratios. The molar ratio of Triton X-100 to lipid was kept constant at 4 to 1. Labeling one lipid with 3H and the other lipid with 14C enabled us to determine the hydrolysis of both components of these binary lipid mixed micelles. We found that the hydrolysis of phosphatidylcholine was activated by the inclusion of small amounts of phosphatidic acid (2.5-fold), phosphatidylethanolamine (1.5-fold) or phosphatidylserine (1.4-fold). The maximal activation of phosphatidylcholine hydrolysis was observed when 5 mol% of phosphatidylethanolamine, 7.5 mol% phosphatidic acid or 5 mol% phosphatidylserine was added to Triton X-100 mixed micelles. The hydrolysis of phosphatidic acid was activated 30%, and that of phosphatidylserine was inhibited 30% when the molar proportion of phosphatidylcholine was less than 50 mol%. The hydrolysis of phosphatidylethanolamine was slightly activated when the mol% of phosphatidylcholine was below 5. The hydrolysis of phosphatidylserine was inhibited by phosphatidylethanolamine when the mol% of the latter was 50 or less whereas phosphatidylethanolamine hydrolysis was not affected by phosphatidylserine. Under the conditions used sphingomyelin and cholesterol did not have a significant effect on the hydrolysis of the phospholipids studied. In agreement with our previous study (Kucera et al. (1988) J. Biol. Chem. 263, 1920 1928) these studies show that the phospholipid polar head group is an important factor which influences the action of hepatic lipase and that the interfacial properties of the substrate play a role in the expression of the activity of this enzyme. The molar ratios of phosphatidic acid, phosphatidylethanolamine and phosphatidylserine which activated phosphatidylcholine hydrolysis correspond closely to the molar ratios of these lipids found in the surface lipid film of lipoproteins e.g., high density lipoproteins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2223859 TI - Eutectic interactions between saturated and unsaturated chain cholesteryl esters: comparison of calculated and observed phase diagrams. AB - Binary phase behavior of saturated chain with unsaturated chain cholesteryl esters is evaluated by analysis of the phase diagrams in terms of ideal solution theory. Cholesteryl palmitate, which crystallizes in the bilayer structure, forms a eutectic with either cholesteryl oleate or cholesteryl linoleate and, as indicated by low angle X-ray data, the components are nearly totally fractionated in the solid state. The fit of the two experimental liquidus curves by a calculation of freezing point depression for an ideal solution indicates that the molecular interactions are nonspecific in the binary liquid state. Cholesteryl caprylate and cholesteryl oleate, both of which crystallize as the monolayer II form, also form a eutectic. X-ray data again indicate nearly total fractionation. The liquidus curve is reasonably well matched by calculation of ideal freezing point depression. However, dissimilar molecular volumes can cause the melt cholesteric transition line to deviate from an ideal concentration dependence. Possible fractionation mechanisms for cholesteryl esters in arterial lesions are thereby indicated. For example, when the molecules have greatly different volumes, clustering can occur in the liquid crystalline state. Even when the molecular volumes are similar, the saturated component can solidify in regions where it is relatively abundant, because of the incompatibility of two crystal structures with greatly different layer structures. PMID- 2223860 TI - Rates of lipogenesis and plasma insulin concentrations in inbred lines of mice differing in fatness. AB - Rates of lipogenesis de novo and plasma concentrations of insulin were compared during post-natal growth in two inbred lines of mice (VL/fDk (VL) and SWR/fNIMR (SWR] in which differences in growth and fatness are probably due to multiple not single gene effects. Irrespective of sex, the lipogenic rate/g was higher in the fatter VL mice in the liver and all other tissues except the head, where it was lower, and the gonadal fat pad, where it was not different. Adult mice in general had lower lipogenic rates than those measured soon after weaning. In both lines the lipogenic rate/g of tissue was higher in males in the liver and in females in the gonadal fat pad. Plasma insulin concentrations were higher in VL mice and tended to rise with age. These results demonstrate that metabolic differences associated with differences in fatness in inbred lines of mice in which fatness is controlled by more than one gene, are qualitatively but not quantitatively similar to those observed by other workers in lines of mice differing in fatness due to a single gene mutation. PMID- 2223861 TI - Lipid peroxidation in rat liver microsomes. II. Response of hydroperoxide formation to iron concentration. AB - When rat liver microsomes were incubated with NADPH, the major products were hydroperoxides which increased with time indicating that endogenous iron content is able to promote lipid peroxidation. The addition of either 5 microM Fe2+ or Fe3+ ions strongly enhanced the hydroperoxide formation rate. However, due to the hydroperoxide breakdown, hydroperoxide concentration decreased with time in this case. Higher ferrous or ferric iron concentration did not change the situation much, in that both hydroperoxide breakdown and formation were similar to those when NADPH only was present in the incubation medium. After lipid peroxidation, analysis of fatty acids indicated that the highest amount of peroxidized PUFA occurred in the presence of 5 microM of either Fe2+ or Fe3+. This analysis also showed that after 8 min incubation with low iron concentration, PUFA depletion was about 77% of that observed after 20 min, whereas without any iron addition or in the presence of 30 microM of either Fe3+, PUFA decrease was only about 37% of that observed after 20 min. As far as the optimum Fe2+/Fe3+ ratio required to promote the initiation of microsomal lipid peroxidation in rat liver is concerned, the highest hydroperoxide formation was observed with a ratio ranging from 0.5 to 2. These results indicate that microsomal lipid peroxidation induced by endogenous iron is speeded up by the addition of low concentrations of either Fe2+ or Fe3+ ions, probably because free radicals generated by hydroperoxide breakdown catalyze the propagation process. In experimental conditions unfavourable to hydroperoxide breakdown the principal process is that of the initiation of lipid peroxidation. PMID- 2223862 TI - Low fatty acid elongation rate in the presence of NADH in the liver endoplasmic reticulum. Overinhibition by BSA at the beta-ketoreductase level. AB - The rate of NADH-dependent palmitoyl-CoA elongation was only 41% of that of NADH dependent elongation in microsomes from rats fed a fat-free diet, in the absence of BSA. This value was markedly lowered to 5%, when the assay was performed in the presence of BSA. The determination of the intermediate products showed that 93% of the total products accumulated as beta-ketostearate in the presence of BSA and NADH, whereas the accumulated beta-ketostearate was only 25% of the total products in the presence of BSA and NADPH. BSA was shown to be responsible for the low rate of NADH-dependent elongation by inhibiting the beta-ketoreductase in the presence of NADH and, thereby, inducing beta-ketostearate accumulation. These results indicate that NADH is probably not the physiological electron donor to the elongation pathway. PMID- 2223863 TI - Role of bovine pulmonary surfactant-associated proteins in the surface-active property of phospholipid mixtures. AB - The surfactant-associated proteins, SP-A, SP-B and SP-C have been isolated from bovine pulmonary surfactant. The biophysical roles of SP-B and SP-C in reconstituted surfactants, with various phospholipid mixtures subjected to different thermal treatments, have been examined using a pulsating bubble surfactometer. The phospholipid mixtures were: (A) dipalmitoylphosphatidylcholine (DPPC)/egg phosphatidylcholine (PC)/egg phosphatidylglycerol (PG) (6:2:2, w/w); (B) DPPC/PG (9:1); and (C) DPPC/PG (7:3). Thermal treatments involved mixing SP-B or SP-C, at room temperature, with lipids in chloroform/methanol (9:1, v/v) and removing the solvent under N2 by (1) evaporation at room temperature; (2) evaporation at 45 degrees C; or (3) incubation at 45 degrees C overnight prior to evaporation at 45 degrees C. In all cases, 45 degrees C solvent evaporation was the most effective treatment. DPPC/egg PG (7:3) was the most favourable lipid composition. With either a static or a pulsating bubble, SP-C promoted a rapid decrease in surface tension with little change thereafter. This implies that SP-C is effective in enhancing phospholipid adsorption but does not play an important role in the removal of non-DPPC lipid from the monolayer. While SP-B was not as effective in facilitating phospholipid absorption, samples containing this protein could achieve near zero surface tension upon pulsation. A very low surface tension could also be attained during the initial pulsation of DPPC/PG plus SP-B mixtures which had been allowed to adsorb until equilibrium. This observation indicates that SP-B promotes the removal of PG from the monolayer. SP A alone had only a slight effect on the surface activity of the DPPC/PG (7:3) mixture, and did not accelerate adsorption of samples containing SP-C. However, SP-A facilitated phospholipid adsorption and may also enhance the removal of PG from monolayers in the presence of SP-B. PMID- 2223864 TI - Inhibition of phospholipase A2 by heparin. AB - Phospholipase A2 (PLA2) is an important enzyme in the regulation of cell behavior. The hydrolysis of phosphatidylcholine in vitro catalyzed by porcine pancreatic PLA2 was inhibited by heparin. Other glycosaminoglycans inhibited PLA2 activity to a significantly lesser extent, with a pattern of inhibition: heparin much greater than chondroitin sulfate (CS)-C greater than CS-A greater than CS-B greater than keratan sulfate. Hyaluronic acid and heparan sulfate caused no inhibition. Heparin's ability to inhibit PLA2 activity did not depend on substrate concentration, but did depend on ionic strength, with inhibition decreasing with increasing ionic strength. Heparin inhibition also varied with pH, being more effective at pH 5-8 than at pH 10. As a consequence, heparin induced a shift of the pH optimum of PLA2 from 7 to 8. Histone IIA and protamine sulfate, heparin-binding proteins, reversed heparin-induced PLA2 inhibition. The concentration of heparin which inhibited PLA2 activity by 50% increased with increasing enzyme concentration. Furthermore, PLA2 bound to heparin-Affigel. The data indicate that the catalytic potential of PLA2 can be regulated by heparin or heparin-like molecules and that inhibition is contingent on the formation of a heparin-PLA2 complex. PMID- 2223865 TI - Purification and characterization of a phospholipase A2 associated with rabbit lung microsomes: some evidence for its mitochondrial origin. AB - Phospholipase A2 (EC 3.1.1.4) activity appeared to be unevenly distributed among the subcellular fractions of rabbit lung homogenates. The mitochondrial/lysosomal fraction, which possessed the highest specific activity, was the second most abundant source of enzyme, following the 1000 x g pellet. Crude microsomes, which were the poorest source of enzyme, had a specific activity intermediate between that of crude mitochondria and of cytosol. Despite these observations, in view of the putative role of microsomal phospholipase A2 in remodelling phosphatidylcholines for pulmonary surfactant biosynthesis, the purification of phospholipase A2 from microsomal membranes was investigated. The activity was solubilized from rabbit lung microsomes with 1 M KCl and resolved into two distinct peaks by ion-exchange chromatography. The larger peak (95% of the recovered activity) was subjected to a combination of hydroxyapatite and gel filtration chromatography, resulting in a purification factor in excess of 70,000 relative to the microsomal membranes. There was no indication for the removal of endogenous inhibitor(s) during the purification. Application of the same purification protocol to a 1 M KCl extract of lung mitochondria resulted in phospholipase A2 profiles in each of the four columns employed that had exactly the same elution characteristics as those generated by the microsomal extracts. The purified enzyme is specific for the sn-2 ester bond of phosphatidylcholine, requires Ca2+ for activity and has an alkaline pH optimum. It is heat-labile and susceptible to treatment by p-bromophenacyl bromide and by 2-mercaptoethanol but remains unaffected by NaF, diisopropylfluorophosphate and thiol reagents. PMID- 2223866 TI - 1,2-Dimethylhydrazine-induced alterations in lipid peroxidation in preneoplastic and neoplastic colonic tissues. AB - To determine whether alterations in lipid peroxidation existed in the preneoplastic and neoplastic colonic tissues of animals treated with the procarcinogen 1,2-dimethylhydrazine, rats were injected subcutaneously with this agent (20 mg/kg body weight per week) or diluent for 5, 10, 15 and 26 weeks. At each of these time periods, animals from both groups were sacrificed, their distal colonic mucosa and/or tumors harvested, and examined and compared with respect to malondialdehyde and lipofuscin-like pigments levels. Additionally, at 26 weeks, the fatty acid composition of microsomes prepared from control, 'uninvolved' and tumor colonic tissues were analyzed and compared. The results of these experiments demonstrated that: (1) the levels of these products of lipid peroxidation were similar in the distal colons of all animals at 5 and 10 weeks; (2) at 15 weeks, however, lipid peroxidation was decreased in the distal colons of animals treated with dimethylhydrazine; (3) at 26 weeks, the levels of these products of lipid peroxidation remained lower in dimethylhydrazine-treated distal 'uninvolved' colonic mucosa and was, moreover, markedly decreased in colonic tumors; and (4) at this latter time period, differences in the fatty acid composition between tumor, 'uninvolved' and control tissues were found. These differences, however, did not appear to underlie the changes noted in the lipid peroxidation products seen in these tissues. Taken together, these findings suggest that alterations in lipid peroxidation may be involved in the colonic malignant transformation process in this experimental model. PMID- 2223868 TI - The occurrence of soluble and membrane-bound non-specific lipid transfer protein (sterol carrier protein 2) in rat tissues. AB - The occurrence and subcellular distribution of the non-specific lipid transfer protein (nsL-TP; sterol carrier protein 2) in rat tissues was investigated by the immunoblotting technique using the affinity purified antibody against rat liver nsL-TP. Highest levels of the protein were found in the homogenates of liver, lung and adrenals, whereas it could hardly be detected in brain. In other tissues (i.e., testis, kidney, heart and intestine) the protein was present at intermediate concentrations. Analysis of subcellular fractions obtained by differential centrifugation demonstrated that in all tissues except for the liver, nsL-TP was predominantly present in the particulate fractions. In the particulate fractions of all tissues, an immunoreactive 58 kDa-protein was detected. Density centrifugation of a nuclear-free homogenate from liver and testis indicated that the 58 kDa-protein did, and nsL-TP did not, cofractionate with catalase. This suggests that in these tissues the bulk of nsL-TP is extraperoxisomal. Membrane-bound nsL-TP in testis was sensitive to trypsin treatment, suggesting that it is exposed to the cytosol. Release of nsL-TP by washing the membranes with 0.1 M Na2CO3 (pH 11.5), indicated that nsL-TP is a periferal protein. It was shown by chromatofocussing that nsL-TP extracted from membrane fractions was more basic than nsL-TP present in the cytosol fraction from rat liver (isoelectric point of 8.7). PMID- 2223867 TI - Metabolism of fatty acids and their incorporation into phospholipids of the mitochondria and endoplasmic reticulum in isolated hepatocytes determined by isolation of fluorescence derivatives. AB - Isolated hepatocytes were incubated in the presence of [14C]palmitic, [14C]linoleic or [14C]linolenic acid and the time-courses of incorporation of radioactivity into phosphatidylcholine and phosphatidylethanolamine of microsomes and mitochondria were followed. For this purpose a procedure was developed for HPLC separation of 9-diazomethylanthracene (ADAM) derivatives of fatty acids. When [14C]palmitic acid was used, the major product of elongation and desaturation was octadecadienoic acid, which accounted for 35-65% of the total radioactivity. Labeled palmitoleic, stearic and oleic acids could also be isolated. In fatty acids which do not participate to any large extent in deacylation-reacylation reactions, the pattern of incorporation was characteristic: a high rate of incorporation into microsomal and a low rate of incorporation into mitochondrial phospholipids during the first 40 min, followed by a decrease in the former and an increase in mitochondrial labeling. This pattern is consistent with the fact that de novo synthesis of these two phospholipids occurs in the endoplasmic reticulum in vivo. When cells were incubated in the presence of [14C]linoleic acid, 70-90% of the radioactivity recovered in phospholipids was in this same form, whereas the remaining label was mainly in arachidonic acid and, to some extent, in eicosatrienoic acid. When hepatocytes were incubated in the presence of [14C]linolenic acid, 70-85% of the radioactivity in isolated phospholipids was associated with linolenic acid. As much as 20% of the label was recovered in docosahexanoic acid and 5-10% in arachidonic acid. In the case of the two latter labeled substrates the exchange reactions seem to dominate over de novo synthesis. For phospholipids synthesized de novo the transfer from the endoplasmic reticulum to mitochondria requires about 3 h. PMID- 2223869 TI - Cholesterol metabolism in dystrophic mice. II. Altered enzyme activities. AB - In a previous study we found that free cholesterol (FC) and cholesterol ester (CE) concentrations in fast-glycolytic (FG) muscle tissue from dystrophic mice are significantly higher than normal. This increase is not due to an increased capacity for de novo cholesterol biosynthesis. HMG-CoA reductase (HMGR) (the enzyme which catalyzes the rate limiting step) activity is significantly decreased in dystrophic muscle compared to normal. This decrease is paralleled by an increased capacity for both CE production and hydrolysis, i.e., both Acyl CoA:cholesterol acyltransferase (ACAT) activity and the activities of both lysosomal and sarcoplasmic cholesterol ester hydrolases (CEH) are greatly increased. These enzyme changes in dystrophic FG muscle are similar those observed in normal tissues with elevated levels of cholesterol, which suggests that such changes are not the cause of the altered cholesterol concentrations but are rather the response of the tissue to elevated levels of cholesterol. PMID- 2223870 TI - A 31P-NMR study of phosphate transport and compartmentation in Candida utilis. AB - The recovery of Candida utilis from phosphate starvation was studied using 31P NMR. The phosphate analogue methylphosphonate was found to be a useful indicator of cytosol pH. Added orthophosphate was rapidly accumulated by the cells and stored mainly In a stable pool of polyphosphate of mean chain-length at least 200 units. Observed pH changes in the medium and cytosol during uptake of orthophosphate and methylphosphonate are consistent with the transport of these compounds across the plasma membrane by a proton/phosphate symport. However, transport of phosphate across the vacuole membrane occurs by a mechanism for which methylphosphonate is not a substrate. In the cytosol pH changes are strongly correlated with changes in orthophosphate concentration, however, this is not the case in the vacuole. PMID- 2223871 TI - Phosphatic metabolites, intracellular pH and free [Mg2+] in single, intact porcine carotid artery segments studied by 31P-NMR. AB - Superfused porcine carotid artery segments (approximately 7 cm lengths) were analyzed by 31P-NMR spectroscopic methods to characterize the 31P spectrum of arterial smooth muscle and to determine the influence of passive stretch (intraluminal pressurization, 95-100 mmHg) on cellular phosphatic metabolite levels, intracellular pH and free magnesium concentration ([Mg2+free]i). Equilibrated, single, intact arteries were studied under steady-state, constant flow conditions at 37 degrees C. Phosphoethanolamine, phosphocholine, inorganic phosphate (Pi), phosphocreatine (PCr) and nucleoside triphosphates (NTP), primarily ATP, were the principle metabolites detected in the 31P-NMR spectrum of intact arterial smooth muscle. The concentration of these metabolites and intracellular pH, as determined from the referenced chemical shift of Pi, were unaffected by pressurization. The PCr:Pi ratios determined for nonpressurized (flaccid) and pressurized arteries were 1.2 +/- 0.1 and 1.3 +/- 0.3, respectively. Intracellular pH averaged 7.02 +/- 0.02 (mean +/- 1 S.D.) for flaccid arteries vs. 7.03 +/- 0.05 for pressurized arteries. The upfield chemical shift of the beta-ATP peak, which has been described in other types of smooth muscle, was also observed in these experiments. Interestingly, pressurization significantly shifted the resonance position of this peak, which was interpreted to represent a change in [Mg2+free]i. The average [Mg2+free]i of flaccid artery preparations was computed to be 0.54 +/- 0.03 x 10(-3) M, as compared to 0.99 +/- 0.10 x 10(-3) M for pressurized arteries. This change in [Mg2+free]i was evident within the first hour following pressurization and persisted thereafter. These findings suggest that altering the resting length of vascular smooth muscle produces a change in [Mg2+free]i. This shift in free Mg2+ levels may act as a metabolic signal triggering a change in vascular smooth muscle metabolism, an effect which has been reported to occur in smooth muscle in response to stretch. PMID- 2223872 TI - Bilirubin-neural cell interaction: characterization of initial cell surface binding leading to toxicity in the neuroblastoma cell line N-115. AB - The toxicity of bilirubin to the nervous system might be due to its effect on several key enzyme reactions occurring in the intracellular compartment as suggested by in vitro studies. The question of how bilirubin, a molecule with poor solubility in water and organic solvents, interacts with the plasma membrane and reaches intracellular targets is unclear. In an attempt to get some insight into this problem, we have measured the uptake of bilirubin from bilirubin albumin solutions by the murine neuroblastoma cell line N-115. At a constant total concentration of bilirubin, the initial rate, as well as the extent of uptake, increases with increasing bilirubin to albumin molar ratio (B/A). The binding is reversible, at least partially, as indicated by the ability of albumin to extract cell-bound bilirubin. The cellular uptake of bilirubin was found to depend also on the concentration of bilirubin, on temperature and on pH. The results are not consistent with either a carrier-mediated transport or passive diffusion across the plasma membrane. The data, however, seem to fit a multistep binding of bilirubin to the plasma membrane proposed for the interaction of bilirubin with synaptosomal plasma membrane vesicles, erythrocyte ghosts and lipid vesicles. These studies, thus, reveal the complexity of the binding interaction at the level of the plasma membrane and leave open the question of transport across the membrane. PMID- 2223873 TI - Insulin secretagogues induce Ca(2+)-like changes in cytoplasmic Mg2+ in pancreatic beta-cells. AB - The effects of insulin secretagogues on the cytoplasmic Mg2+ concentration ([Mg2+]i) of pancreatic beta-cells were studied in suspensions and in individual beta-cells using dual-wavelength fluorometry and the indicator mag-fura-2. Average [Mg2+]i was in the 800-900 microM range in a medium containing 3 mM glucose. When the sugar concentration was raised to 20 mM, the cells reacted with an initial lowering of [Mg2+]i followed by an increase. The sugar apparently also stimulated leakage of the Mg2+ indicator. Addition of 100 microM tolbutamide or raising the K+ concentration by 25 mM caused relatively rapid increases of [Mg2+]i. Methoxyverapamil prevented the [Mg2+]i-increasing actions of glucose, K+ and tolbutamide. The greatest change in [Mg2+]i was obtained when beta-cells were exposed to 100 microM carbachol. In this case there was a more than 10% lowering, which was reversed upon removal of the agonist. Measurements of [Mg2+]i are important not only for understanding fluctuations of this ion, but may also aid to elucidate the mechanisms involved in the regulation of cytoplasmic Ca2+. PMID- 2223874 TI - The mammalian dihydrofolate reductase locus. PMID- 2223876 TI - The yeast 5S rRNA binding ribosomal protein YL3 is phosphorylated in vivo. AB - The 5S rRNA-ribosomal protein YL3 ribonucleoprotein particle was isolated from yeast cells labeled with [32P]orthophosphate. The protein moiety was purified and found to be radioactive. Labeled phosphoserine was detected after partial hydrolysis of the protein. Up to two phosphate residues are sterified per mole of YL3 ribosomal protein. PMID- 2223875 TI - Evidence for DNA binding activity of numatrin (B23), a cell cycle-regulated nuclear matrix protein. AB - Stimulation of various cell types with growth factors is associated with a rapid induction in the synthesis of a nuclear matrix protein, termed 'numatrin' which was shown to be identical to the nucleolar protein B23. The abundance of numatrin was shown to be correlated with entry and progression through the S-phase. Thus, experiments were undertaken to examine whether numatrin also has DNA binding activity. Using whole nuclear extract, we showed that numatrin binds to both double-stranded (DS) DNA and to single-stranded (SS) DNA cellulose columns. Purified numatrin, which was extracted either under native conditions (in oligomeric form) or under urea conditions (in monomeric form), demonstrated significant binding to either [3H]DS-DNA or [3H]DS-DNA as shown by nitrocellulose filter binding assay. However, numatrin binding to DS-DNA was qualitatively and quantitatively different from its binding to SS-DNA. Thus, the binding of numatrin was several fold higher to DS-DNA as compared to SS-DNA. The binding to DS-DNA was reduced by 77% in the presence of 0.5 M NaCl, while the binding to SS DNA was not affected under this condition. Furthermore, treatment of the native numatrin under conditions which caused monomerization of the protein resulted in a significant enhancement of numatrin binding to SS-DNA but did not affect the binding to DS-DNA. Following heparin-Sepharose chromatography purification (under native conditions), numatrin at picomole amounts showed significant binding to both DS-DNA and SS-DNA. Finally, numatrin was found to copurify with the complex of DNA polymerase alpha primase together with other proteins required for SV-40 in vitro replication activity. These results demonstrate that numatrin has DNA binding activity, and imply a possible role for numatrin/B23 in DNA-associated processes. PMID- 2223877 TI - Genetic engineering, isolation and characterization of a truncated Escherichia coli elongation factor Tu comprising domains 2 and 3. AB - A deletion mutant of a plasmid born Escherichia coli tufA gene, which codes for a truncated elongation factor Tu comprising domains 2 and 3, has been constructed by genetic engineering. This gene was overexpressed in E. coli, and a polypeptide representing the truncated elongation factor Tu was isolated, purified to near homogeneity, crystallized and characterized physico-chemically as well as biochemically. Circular dichroism spectroscopy and limited tryptic digestion demonstrate that the isolated domain pair 2 and 3 behaves like an independent folding unit which adopts a similar secondary and most likely, tertiary, structure to that present in the intact elongation factor Tu. However, the isolated domain pair 2 and 3 does not interact with aminoacyl-tRNA or the antibiotic kirromycin, two ligands which were shown previously by cross-linking experiments to be in contact with amino acid residues located in domains 1 and 2, and domain 3, respectively. The results suggest that the isolated domain pair 2 and 3 by itself forms too few contacts with these ligands to form a stable complex. Furthermore, the data suggest that domain 1 in intact EF-Tu, in a subtle but nevertheless decisive manner, alters the conformation of the other two domains in such a way that all three domains cooperatively create a high affinity binding site for aminoacyl-tRNA and the antibiotic kirromycin. PMID- 2223878 TI - Mammalian drug resistant mutants with multiple gene amplifications: genes encoding the M1 component of ribonucleotide reductase, the M2 component of ribonucleotide reductase, ornithine decarboxylase, p5-8, the H-subunit of ferritin and the L-subunit of ferritin. AB - Hydroxyurea was used to select two very highly drug resistant cell lines, designated HR-15 and HR-30. Both drug resistant lines contained elevated levels of ribonucleotide reductase activity. Northern and Southern blot analysis indicated that the two drug resistant lines contained increased levels of mRNA for the two components, M1 and M2, of ribonucleotide reductase, and M1 and M2 gene amplifications. Alterations in M1 and M2 protein levels were also evident in Western blot analysis. Further studies of HR-15 and HR-30 cells by Northern and Southern blot analysis showed that the drug resistant cell lines had elevated levels of ornithine decarboxylase mRNA and p5-8 mRNA, as well as increased ornithine decarboxylase and p5-8 gene copy numbers, respectively. Furthermore, characterization of HR-15 and HR-30 drug-resistant cell lines revealed increased mRNA levels for both H- and L-ferritin. Both cell lines exhibited by Southern blot analysis, amplification of the H- and L-ferritin genes. Increases in the cellular levels of H- and L-ferritin subunit proteins were also observed in both HR-15 and HR-30 cells, by Western blot analysis. This is the first description of mutant cell lines containing this complex combination of modified gene expressions and gene amplifications. The alterations exhibited by these lines confirm and extend present models of hydroxyurea resistance, are in agreement with and help substantiate models of ribonucleotide reductase regulation and provide interesting links between the expressions of several cellular activities important in proliferation. PMID- 2223879 TI - Cation-dependent solubilization of rat thymocyte chromatin is closely related to decondensation of the nuclei. AB - The cation-dependent solubilization of rat thymocyte chromatin has been compared with decondensation of the nuclei as a function of sodium phosphate-mediated changes in the concentration of Mg2+ and Na+. After digestion of the nuclei with DNase I or Micrococcus nuclease for a time just sufficient to permit extraction of a maximal amount of chromatin (minimum digestion), solubilization of most of the chromatin was found to occur with the same cation dependency as decondensation of untreated nuclei, while further digestion changed the ionic requirements for solubilization. The cation-dependency of the chromatin solubility and of the nuclear decondensation also exhibited the same variations with temperature. The chromatin in the nuclei became up to 4-times more sensitive to DNase I by decondensation, which also induced a shift in the DNase I cleavage mode from a 200 bp to a 100 bp repeat pattern. In contrast, the sensitivity to Micrococcus nuclease appeared to be nearly unchanged. These results suggest that solubilization of chromatin prepared by a mild endonuclease treatment occurs as a direct consequence of structural changes in the chromatin which take place during decondensation of the nuclei. PMID- 2223881 TI - Unique hairpin structures occurring at the replication origin of phage G4 DNA. AB - Recently we reported that a DNA fragment, GCCAAAGC, forms an extraordinarily stable hairpin structure with two G-C pairs at the terminus and A-A-A stacked structure. The sequence is present at the replication origin of bacteriophage G4 ssDNA, and so on. Several kinds of possible hairpin structures, corresponding to the replication origin of phage G4, were synthesized and their secondary structures were examined. It was found that the fragments are able to form interconvertible hairpin structures depending on the length of the base-paired regions. The hairpin structure consisting of GCGAAAGC was not digested by the exonuclease activity of T4 DNA polymerase and it was stable enough to be only minimally bound by a single-stranded DNA binding protein. PMID- 2223880 TI - Structural organization of the human CaMIII calmodulin gene. AB - The complete structural organization of the human calmodulin III gene has been determined. This gene specifies the mRNA represented by the previously reported cDNA ht6. The gene contains six exons spread over a total of approx. 10 kb of DNA. Its exon-intron organization is identical to that of the only known chicken calmodulin gene and to that of two of the three characterized rat calmodulin genes. As in many other genes encoding Ca2+ binding proteins, intron 1 separates the ATG initiation codon from the remainder of the coding region. The major and two minor sites of transcription initiation have been determined by primer extension and ribonuclease protection assays. The DNA sequence in the promoter and 5' untranslated region is extremely GC-rich. No typical TATA and CAAT boxes are present upstream of the major transcriptional start site; however, a consensus CAAT box sequence is found further upstream and may play a role in transcriptional initiation from the minor start sites. Six sequence elements with high similarity to monkey SV40-like Sp1-binding regions are present in the putative promoter region, two of which contain perfect GGGCGG core sequences. The structure of the human calmodulin III gene promoter indicates that this gene belongs to a class of 'house-keeping' genes but that its level of expression may also be specifically regulated. PMID- 2223882 TI - Expression of active human hypoxanthine-guanine phosphoribosyltransferase in Escherichia coli and characterisation of the recombinant enzyme. AB - A plasmid, pRG1, has been constructed by incorporating the coding sequence of human hypoxanthine-guanine phosphoribosyltransferase (HPRT) into the expression vector pT7-7. Expression of human HPRT has been achieved in HPRT- Escherichia coli cells transformed with pRG1 and pGP1-2, as shown by: (1) exclusive labelling with [35S]methionine of a polypeptide with the same mobility as purified human HPRT on SDS-PAGE; and (2) measurement of HPRT activity after cell lysis. Although the majority of the recombinant HPRT was present in the particulate fraction after cell lysis and centrifugation, sufficient HPRT activity was present in the supernatant fraction to allow comparison with the HPRT purified from human erythrocytes and the activity in human haemolysates and lymphoblast lysates. Small differences in electrophoretic mobility on native gels were found between HPRT activity from these sources. The Km values of recombinant HPRT for the substrates 5-phospho-alpha-D-ribosyl-1-pyrophosphate and guanine were compared with those of lymphoblast and erythrocyte HPRT. PMID- 2223883 TI - Partial apolipoprotein E-beta-galactosidase fusion protein expressed in Escherichia coli retains binding activity to the LDL(B/E) receptor. AB - A partial rat apo E-beta-galactosidase fusion protein was produced in Escherichia coli Y1089 infected with recombinant lambda GT11 obtained by immunoscreening of a rat liver cDNA library with an anti-rat LDL antiserum. Partial cDNA overlapped the apo E mRNA sequence coding for apo E binding domain towards the LDL(B/E) receptor up to codon for Arg-139. Fusion protein specifically bound to human fibroblasts. The high-affinity component exhibited a Kd of 5 x 10(-8) M and 4.1 x 10(5) sites per cell. Fusion protein binding to fibroblasts was mediated by their apo E moiety and not by beta-galactosidase since: (1) specific binding of fusion protein was competed out by human LDL; (2) beta-galactosidase did not compete with fusion protein binding; and (3) human fibroblasts from a patient with familial hypercholesterolemia, deficient in LDL(B/E) receptor, bound fusion protein 10-times lower than control fibroblasts. It was demonstrated that partial fusion protein retained the functional activity of the native apo E. However, compared to full-length native or engineered apo E, fusion protein was able to bind fibroblasts without being complexed with phospholipids. Fusion proteins might be a useful tool for studying the functional efficiency of the LDL(B/E) receptor and for mapping residues and domains involved in the binding process. PMID- 2223884 TI - Glutaminyl-tRNA synthetase as a component of the high-molecular weight complex of human aminoacyl-tRNA synthetases. An immunological study. AB - The human glutaminyl-tRNA synthetase is three times larger than the corresponding bacterial and twice as large as the yeast enzyme. It is possible that the additional sequences of the human glutaminyl-tRNA synthetase are required for the formation of the multienzyme complex which is known to include several of aminoacyl-tRNA synthetases in mammalian cells. To address this point we prepared antibodies against three regions of the human glutaminyl-tRNA synthetase, namely against its enzymatically important core region, and against two sections in its large C-terminal extension. In intact multienzyme complexes the core region was accessible to specific antibody binding. However, the C-terminal sections became available to specific antibody binding only when certain components of the multienzyme complex were either absent or degraded. These findings allow first conclusions as to the relative position of some components in the mammalian aminoacyl-tRNA synthetase complex. PMID- 2223885 TI - Islet amyloid polypeptide: structure and upstream sequences of the IAPP gene in rat and man. AB - Islet amyloid polypeptide (IAPP) or amylin is a pancreatic islet hormone which was first found in amyloid in insulinomas and in pancreases of patients with type 2 diabetes. In rat a similar polypeptide occurs; however, pancreatic amyloid in this species has not been described. Here we report the structure of the rat and human IAPP gene. Both consist of three exons and two introns which are very similar. The upstream sequence of the rat IAPP gene contains a TATA-box, a CCAAT sequence and a GT-element, whereas the upstream sequence of the human IAPP gene contains a TATA-box and a rat insulin enhancer-like sequence. This suggests that the rat and human IAPP gene may be controlled differently at the transcriptional level. PMID- 2223886 TI - Nucleotide sequence of cDNA and primary structure for hard tail growth hormone. AB - Full-length cDNA for hard tail growth hormone (htGH) has been cloned, and the nucleotide and deduced amino acid sequences have been analyzed. htGH is composed of 188 amino acid residues, and it shows 79, 74, 72, 59, 56, 37, 33 and 30% identity of amino acid with yellow tail, tuna, sea bream, flounder, salmon, blue shark, bullfrog and human GHs, respectively. PMID- 2223887 TI - A novel creatine kinase cDNA whose transcript shows enhanced testicular expression. AB - A cDNA (TCK1) encoding a creatine kinase (CK) subunit has been isolated from a cDNA library prepared from rainbow trout testis poly(A) + RNA. The predicted amino acid sequence for this CK subunit showed a novel amino-terminal coding region. Northern blot analyses demonstrated preferential expression of this CK subunit in testis relative to other CK containing organs. Southern blot analysis suggested a single copy number for this CK gene. PMID- 2223889 TI - On clinical efficacy: why biofeedback does--and does not--work. AB - Questions of clinical efficacy are becoming more prominent in this era of diminishing funds for research and clinical care, and new treatment procedures, in particular, are being rigorously scrutinized. This presents a challenge for the relatively recent field of biofeedback and applied psychophysiology. This field has a strong scientific orientation and a rapidly expanding research base, which includes many well-controlled clinical outcome studies. The point is raised, and illustrated with data from current clinical outcome studies, that it is time for a shift in emphasis away from simply piling study upon study and toward more thoughtful interpretation of experimental and clinical findings and the development of a clearer conceptual framework for biofeedback therapy and research. PMID- 2223888 TI - Mouse asialoglycoprotein receptor cDNA sequence: conservation of receptor genes during mammalian evolution. AB - The asialoglycoprotein receptor internalizes galactose-terminated glycoproteins into mammalian hepatocytes for degradation in lysosomes. We report the cloning and sequencing of one murine asialoglycoprotein receptor cDNA which exhibits homology with rat and human receptor forms. Conserved regions may correlate with functional domains. The membrane-bound M (mouse) HL polypeptide does not contain a cleavable N-terminal signal sequence and is probably anchored to the membrane via an internal insertion sequence. PMID- 2223890 TI - Biofeedback treatments of essential hypertension. AB - Fifteen years of research in the self-regulatory treatment of hypertension by the author is summarized. A model relating expectations, task performance, home practice, and biochemical variables to the thermal biofeedback treatment of hypertension is presented. PMID- 2223891 TI - Exercise intervention attenuates emotional distress and natural killer cell decrements following notification of positive serologic status for HIV-1. AB - The impact of aerobic exercise training as a buffer of the affective distress and immune decrements which accompany the notification of HIV-1 antibody status in an AIDS risk group was studied. Fifty asymptomatic gay males with a pretraining fitness level of average or below (determined by predicted VO2 max) were randomly assigned to either an aerobic exercise training program or a no-contact control condition. After five weeks of training, at a point 72 hours before serostatus notification, psychometric, fitness and immunologic data were collected on all subjects. Psychometric and immunologic measures were again collected one-week postnotification. Seropositive controls showed significant increases in anxiety and depression, as well as decrements in natural killer cell number following notification whereas, seropositive exercisers showed no similar changes and in fact, resembled both seronegative groups. These findings suggest that concurrent changes in some affective and immunologic measures in response to an acute stressor might be attenuated by an experimentally manipulated aerobic exercise training intervention. PMID- 2223892 TI - Effects of paced respiration on anxiety reduction in a clinical population. AB - The purpose of this study was to examine the effects of paced respiration on autonomic and self-report indices of affect within a clinical population. Thirty six alcohol-dependent inpatients scoring high in trait anxiety were randomly assigned to either a pacing or attention control group. The paced subjects received 10 minutes of slow-breathing training during the first experimental session, while control subjects simply counted the pacing tones. In a second session, paced subjects were asked to breathe at the same lowered rate (10 cycles per minute) on their own, while the remaining subjects were instructed to relax. Prior to and following each session, self-ratings of tension level and state anxiety were collected. As expected, paced subjects evidenced greater reductions in self-rated tension, state anxiety, and skin conductance levels compared to the control subjects. It was concluded that respiratory pacing is an easily learned self-control strategy and potentially may be a useful therapeutic tool. PMID- 2223893 TI - Structural classification of multi-input nonlinear systems. AB - We present new structural classification and parameter estimation results that are applicable to multi-input nonlinear systems. The mathematical relationships between the self- and cross-(Volterra and Wiener) kernels are derived for a basic two-input nonlinear structure. These results are then used to develop classification methods for more complicated two-input structures. Algorithms for estimating the parameters (linear and nonlinear subsystems) of these structures are also presented. PMID- 2223894 TI - Some conjectures on the design of a rod outer segment. AB - Photoreceptor diameter and spacing have been extensively analyzed with respect to diffraction, wave-guiding and other phenomena and have been found to be consistent with optimal design criteria. Photoreceptor length, on the other hand, has received but little attention. It is proposed here that the outer segment length of rods is optimal with respect to the competing demands of maximal photon absorption and minimal noise. This is borne out by our calculations based on the experimental data. PMID- 2223896 TI - [Biochemistry of organometallic compounds]. AB - Recent studies have demonstrated that organometallics can be substrates of enzymes and may undergo biotransformations in the presence of microorganisms. Latest achievements in organometallic biosynthesis, applications of organometallics in biosensor systems and the properties and models of novel enzymes which attack the core of organometallic compounds, i.e., the metal-carbon bond, are discussed. PMID- 2223895 TI - Postural maintenance during movement: simulations of a two joint model. AB - Voluntary movements of the upper body are accompanied by anticipatory postural adjustments to the lower body in a standing subject. The long-standing hypothesis is that these anticipatory adjustments serve to counteract the perturbation to the body's center of gravity caused by the voluntary arm movement. This paper presents model simulations investigating the possible roles of anticipatory postural activity that accompanies a rapid, upward arm swing. The model incorporates two (idealized) antagonistic muscle pairs controlling the movements of a double-joint system, with a "shoulder joint" between the arm and stiff body links, and an "ankle joint" between the stiff body-leg segment and the ground. Each muscle is represented by a nonlinear viscoelastic element and also includes proprioceptive feedback. Four inputs to the model define the motor control signals for muscle force generation in both the arm and the postural muscle pairs. The neurological component of the model describes consequences of alternate strategies for cocontractions, stretch reflex activity, and anticipatory and synchronous postural activities (or combinations thereof). Simulations with this model show that: (1) none of the postural maintenance schemes considered in these simulations (including varying anticipation) could suppress the initial backward thrust on the body link; (2) the more important destabilizing perturbation is a subsequent forward sway that, left uncountered by postural activity, would eventually leave the body to fall flat on its face; and (3) anticipatory silencing of the postural extensor followed by a brief period of extensor activation (descending control) and synchronous reflex activity (feedback control) appears to be the most likely postural stabilizing strategy that inhibits the continuous forward sway and is consistent with the experimental evidence. PMID- 2223897 TI - [The role of hydroxyl groups of tyrosine residues in RNA-ligase]. AB - The stability of the AMP-RNA-ligase complex was studied. The complex was found to be stable for at least two weeks upon storage at 0 degrees. Approximately 50% of the initial radioactivity was retained after storage at 9 degrees for 49 days. The formation of adenosine in the complex decomposition products suggested the possible involvement of the tyrosine hydroxyl group in the formation of AMP-RNA ligase complexes. In order to study the structure of the enzyme active site, the hydroxyl groups of the RNA-ligase tyrosine residues were modified with N-acetyl imidazole. It was found that four out of 25 tyrosine residues are exceptionally susceptible to chemical modification with resultant complete suppression of the enzyme ability to form a complex with ATP. The kinetic parameters (Km, V) of native and modified RNA-ligase were determined and compared. A hypothetical scheme of the tyrosine hydroxyl group participation in RNA-ligase-catalyzed reactions is proposed. PMID- 2223898 TI - [Diazepam metabolism by multiple forms of cytochrome P-450 in rat liver microsomes]. AB - The synthesis of pharmacologically active diazepam metabolites (oxazepam, 4 hydroxydiazepam, N-demethyldiazepam) in liver microsomes of intact and phenobarbital-, 3-methylcholanthrene- and dexamethasone-induced male and female Wistar rats as well as in a reconstituted system with isolated forms of cytochrome P-450 (P-450a, P-450b, P-450c, P-450d and P-450k according to the Ryan nomenclature) was studied. Marked sex-dependent differences in the rates of diazepam metabolism in liver microsomes of intact and induced animals were revealed. The changes in the spectrum of diazepam metabolites in liver microsomes of induced rats (as compared to control animals) were revealed. In a reconstituted system only phenobarbital-induced cytochromes P-450b and P-450k were found to be active participants of diazepam N-demethylation; none of the isoenzymes tested were shown to be involved in diazepam hydroxylation. PMID- 2223899 TI - [The effect of calmodulin inhibitors and the new cardiotonic drug DPI 201-106 on the formation of interprotein bonds in the cardiac troponin complex]. AB - Using the binding of labeled [125I]troponin C (TnC) to troponin I (TnI) and troponin (TnT) immobilized on a polyvinylchloride matrix, the Ca-dependent formation of interprotein bonds in the cardiac troponin complex and the effects of various drugs on the above reaction were studied. It has been found that in the absence of Ca2+ the dissociation constant, Kd, for the TnC-TnI complex in equal to (2.5 +/- 1.03).10(-7) M. In the presence of Ca2+ the number of binding sites increases twofold; the Kd value for the bonds formed thereby is (1.74 +/- 0.18).10(-7) M. The complex is stable to the effect of 5 M urea. TnC binding to immobilized TnT is nonspecific and is completely abolished by an addition of 5 M urea. DPI 201-106 used at concentrations up to 10(-3) M does not affect the Ca dependent binding of TnC to TnI; trifluoperazine inhibits this interaction by 60%, whereas substance 48/80 inhibits the reaction by 50% when used at a concentration of 210 micrograms/ml. It is supposed that the compounds interacting with TnC affect, primarily, the cation-binding properties of troponin. These compounds can also inhibit the formation of interprotein bonds but only when used at much higher concentrations. PMID- 2223900 TI - [Isolation of low molecular weight cytoplasmic regulators from the rat liver inducing the electrophoretic transport of K+ ions and phosphate across the inner mitochondrial membrane]. AB - A water-soluble thermostable factor from rat liver cytoplasm whose activity decreases during starvation, causes the uncoupling of oxidative phosphorylation and stimulates pyruvate oxidation in rat liver mitochondria. The activity of this factor is insensitive to pronase treatment. Gel filtration and ion-exchange chromatography resulted in three low molecular weight water-soluble fractions which bear a negative charge at alkaline values of pH and induce electrophoretic transport of K+ and phosphate across the inner mitochondrial membrane. The effect of this factor on K+ transport is manifested at pH less than or equal to 7.0, that on phosphate transport-at pH 6.5-7.6. PMID- 2223901 TI - [DNA-bound lipids from eukaryotic (loach spermatozoa, pigeon erythrocytes) and prokaryotic (E. coli B, phage T2) cells]. AB - Using thin-layer chromatography, some specific DNA-bound neutral lipids and phospholipids of loach spermatozoa, pigeon erythrocytes, E. coli B and phage T2 cells were studied. These lipids are represented by loosely and firmly bound components. The content of neutral lipids in the above DNAs (per mg of DNA) is 10.6, 4.8, 7.81 and 1.43 micrograms, respectively; that of phospholipids is 4.31, 1.28, 1.14 and 0.54 micrograms, respectively. The eucaryotic DNA-bound lipids are highly deficient of free cholesterol, phosphatidylcholine, phosphatidylinositol and phosphatidylserine but are rich in cardiolipin, phosphatidylethanolamine, cholesterol esters, diglycerides and free fatty acids. The quantitative and qualitative composition of DNA-bound lipids of loach spermatozoa changes during the transition from the superhelical to the relaxed conformation of DNA. Procaryotic DNA-bound neutral lipids are also represented by the free cholesterol, diglyceride and free fatty acid fractions, whereas the DNA-bound phospholipids of procaryotes consist of only two fractions, i.e., cardiolipin and phosphatidylethanolamine. The role of DNA-bound lipids in the structural and functional organization of eucaryotic and procaryotic genomes is discussed. PMID- 2223902 TI - [The effect of translation inhibitor cycloheximide on expression of mammalian genes]. AB - The data concerning the cycloheximide influence on individual mRNA content, transcription rate and chromatin structure in mammalian cells are reviewed. The putative mechanism of cycloheximide effect is explained as being due to the existence of short-living regulatory proteins. It is concluded that cycloheximide is a helpful tool in the study of regulation of gene expression in mammalian cells. PMID- 2223903 TI - [Various physico-chemical and kinetic properties of metalloproteinase from bacteriolytic lysoamidase preparation]. AB - The amino acid composition of metalloproteinase was determined. It was shown that the enzyme is made up of four cysteinyl residues which makes it distinct from other known neutral metalloproteinases from Bacillus brevis, Bacillus subtilis and thermolysine that are devoid of cysteinyl residues. The inhibiting effect of amino acids and some di- and tripeptides on the metalloproteinase activity was studied. The pH-dependence of the Michaelis constant (pKm0) of native and diethylpyrocarbonate-modified metalloproteinase (pKm) suggests that the enzyme active center contains two imidazole groups of histidine with pK alpha 1 = 6.75 +/- 0.1 and pK alpha 2 = 5.4 +/- 0.1. The experimental results are compared to those obtained with other microbial metalloproteinases. PMID- 2223904 TI - [Caldesmon and myosin subfragment-1 act differently on the structural state of 1,5-IAEDANS-modified tropomyosin in ghost muscle fibers]. AB - The effect of caldesmon (CD) and subfragment 1 of myosin (S1) on the structural state of tropomyosin (TM) modified with N-(iodoacetyl)-N-(1-naphthyl-5-sulfo) ethylene-diamine (1.5-IAEDANS) in single myosin-free skeletal muscle fibers was studied using polarized microfluorimetry. S1 was performed from skeletal muscles of rabbits, whereas CD and TM were prepared from the smooth muscle of chicken gizzards. An analysis of experimental data revealed that CD initiates and increases the motility of 1.5-IAEDANS-TM, while S1 decreases it. In the presence of CD S1 binding to actin is accompanied by significant changes in the fluorescent label motility. It is supposed that CD and S1 induce in TM conformational changes which interfere with the protein interaction with F-actin. PMID- 2223906 TI - [A method for producing peptide maps of picomolar quantities of protein labelled with the Bolton-Hunter reagent in polyacrylamide gel]. AB - A method of radioiodination to high specific activity by Bolton Hunter reagent of fixed and stained histones in polyacrylamide gel is described. The comparative peptide maps of the histones H1 and H3, labelled in solution and the gel are presented. PMID- 2223905 TI - [The mechanism of photodamage of eye structures. IV. Changes in the reactivity of crystalline SH-groups during UV irradiation]. AB - The kinetics of individual crystalline SH-group modification by DTNB were studied. According to the rates of their interaction with the modifier, the thiol groups in the native protein molecule can be classified as free, accessible, weakly modified and "masked" ones. Denaturation by the detergent (CTAB) caused an increase in the SH-group modification rate. In this case the SH-groups were modified as free and accessible ones. Illumination with UV-light resulted in a decrease in the number of SH-groups, opening of "masked" SH-groups in almost all crystallines except for alpha-crystalline, and essential changes in the SH-group modification rate. PMID- 2223907 TI - [The effect of acute alcoholic intoxication on the morphofunctional properties of the peripheral blood erythrocytes]. AB - In experiments on rabbits it has been established that the acute alcoholization causes prolonged uncompensated alterations of such physical and chemical properties of erythrocytes as the average volume, the concentration of dry substance and water, the density, the content of endoerythrocytal hemoglobin, as well as the concentration of erythrocytes and hemoglobin in blood. PMID- 2223908 TI - [The evaluation of the age-related characteristics of the structural status of the plasma membrane lipid phase in rat fatty tissue by using the method of inductive-resonance energy transfer]. AB - Using the method of inductance-resonance energy transfer from tryptophanyl residues to fluorescent pyrene probe the structural state of plasmatic membranes from adipose tissue of different age rats has been studied. The structural heterogeneity of membrane lipid phase has been revealed. The differences in physical properties of annular and bilayer lipids don't depend on age. During aging the membrane lipid viscosity including lipids of near protein area decreases, the conformation of membrane protein components alters during aging as well. The data on various effectiveness of energy transfer from tryptophanyls to pyrene probe in young and aged animals with stable polypeptide composition of membrane proteins indicates that. The structure of membrane lipid phase is suggested to be the main factor affecting the conformational state and functional activity of membrane-bound proteins during aging. PMID- 2223909 TI - [The microbiological transformation and degradation of pyridine and alkyl pyridines]. AB - The scientific literary data on the microbiological transformation and degradation of pyridine, methylpyridines (picolines), dimethylpyridines (lutidines) and some ethylpyridines are summarized and analysed in this review. These highly toxic compounds are on the one hand the raw materials for medicinal preparation production with microorganisms, on the other hand they are industrial wastes polluting the environment which may be degraded microbiologically. PMID- 2223910 TI - Neonatal and adult patterns of lectin binding to rat small intestinal microvillus membranes. AB - To investigate postnatal developmental changes of rat small intestinal microvillus membrane (MVM) sugar components, binding studies were done using peanut agglutinin (PNA) and soybean agglutinin (SBA). MVM were prepared from rats of different ages (new-borns to 12 weeks). The Airfuge method was used for separation of unbound material. Characteristics of sugar ligand specificity were different for PNA and SBA, although D(+)galactose was used as an inhibitor for both lectins. Concentration curves and Scatchard plots showed partial saturation of total binding, and at least two groups of MVM ligands. Differences in lectin binding between newborn and adult MVM were opposite for PNA and SBA (newborns bound more PNA, but less SBA). During the first few postnatal weeks in rats, SBA binding changed early, and PNA binding exhibited an intermediate change, not related to weaning. Changes in MVM glycoproteins shown by lectin binding appear to be part of a complex postnatal maturational process in rats, involving different biochemical, functional, and biophysical membrane characteristics. PMID- 2223911 TI - Lactate movements in the term human placenta in situ. AB - Movements of lactate through the human placenta in situ were derived from maternal and fetal blood sampling performed under conditions that approximate as closely as possible the normal fetal metabolic state. It is reported that, at the end of pregnancy, the human fetus produces lactate which is transferred to the placenta. The actuality of this lactate transfer coupled with proton transfer is discussed taking into account the results of multiple linear regression analysis determined between the umbilical arterio-venous lactate differences and fetal and maternal lactate and proton concentrations. It is finally assumed that this lactate is partly metabolized in the placenta, the remaining part being transferred from the placenta to the mother. PMID- 2223912 TI - Implantation and in vivo antagonistic effects of antibiotic-susceptible Escherichia coli strains administered to premature newborns. AB - Two antibiotic-susceptible and non-pathogenic Escherichia coli strains were administered to hospitalized premature infants in order to protect them from intestinal colonization by hospital-acquired antibiotic-resistant enteric organisms (EOs). Three groups of 16 premature newborns received respectively strain ECA, strain EMO and both strains simultaneously. A fourth group was used as a control. Resistant EOs became spontaneously established in the digestive tract of a majority of the unadministered children. Both ECA and EMO were able to colonize the digestive tract of a majority of the subjects, and reached high population numbers (greater than 10(7)/g) in the faeces. Both strains appeared as able to reduce significantly the establishment of antibiotic-resistant EOs. This effect was more prominent with EMO, which also impaired the implantation of ECA when both strains had been administered simultaneously. The use of such innocuous microorganisms could thus constitute an additional means of preventing nosocomial infections of intestinal origin. PMID- 2223913 TI - Dependency of Doppler parameters in the anterior cerebral artery on behavioural states in preterm and term neonates. AB - To investigate changes of intracerebral blood flow velocity correlated to different behavioural states, pulsed Doppler measurements were performed on anterior cerebral artery in 12 preterm and term neonates under polygraphic recordings and in view of the infants' behavioural state. Under very strict definition of the behavioural states there were significant differences in the parameters Vm (+25%), Vd (+75%), and Vs (+11%) in active compared to quiet sleep state. MABP was not significantly different in all examined behavioural states. From our results we conclude that in further Doppler studies the infants' behavioural state at the time of measurement should be assessed carefully. PMID- 2223914 TI - Effects of adenosine and its analogues on isolated internal carotid arteries from newborn and adult pigs. AB - Vasorelaxant effects of adenosine and its analogues, 5'-N-(ethylcarboxamide) adenosine (NECA), N6-(l-phenylisopropyl)-adenosine (l-PIA) and N6 cyclohexyladenosine (CHA), on isolated internal carotid arteries from newborn (1 3 days) and adult (6 months) pigs were compared. The order of vasorelaxant potencies of adenosines was: NECA greater than l-PIA greater than adenosine greater than CHA for the adult arteries and NECA greater than l-PIA greater than adenosine = CHA for the newborn arteries. Sensitivities of vessels from the newborn and mature animals to CHA and l-PIA did not differ. However, carotid arteries from the newborn pigs were less sensitive to NECA and adenosine than the adult arteries (p less than 0.05). Theophylline caused an approximately 3-fold shift to the right of the relaxant concentration-response curves to all the four adenosines on arteries from pigs of both age groups. These data suggest that adenosine is not as effective a vasodilator in the newborn as it is in the adult. PMID- 2223915 TI - Effect of a popular Chinese herb on neonatal bilirubin protein binding. AB - A study on the effects of a popular Chinese herb commonly given to newborn infants was undertaken. 'Chuen-Lin', Coptis chinensus/japonicum, which is consumed by 28-51% of Chinese infants, was found to have a significant effect in displacing bilirubin from its serum protein binding as assessed by the peroxidase oxidation method. Taking this herbal tea may thus increase the risk of brain damage by free bilirubin in jaundiced infants. As neonatal hyperbilirubinaemia is highly prevalent among Southern Chinese, the use of Chuen-Lin in the perinatal period must be strongly discouraged. PMID- 2223916 TI - The side effects of lithium. PMID- 2223917 TI - Autoantibodies against brain septal region antigens specific to unmedicated schizophrenia? AB - Health et al. (1989) reported that serum from 96% of unmedicated schizophrenic patients contained IgG autoantibodies specific for the septal region of rhesus monkey brain, compared with 0% of nonschizophrenic control subjects and 6% of schizophrenic patients who were on neuroleptic medication. Using the same technique of crossed immunoelectrophoresis, we have tried to replicate this finding. In contrast to the original report, we observed "positive" precipitin arcs with IgG concentrates from all 14 serum samples tested. The failure of immunoelectrophoretic methods to provide convincing evidence of pathogenic autoantibodies in schizophrenia in no way detracts from the hypothesis that autoimmune processes are involved in some forms of schizophrenia. Such methods have not proved useful in established autoimmune diseases such as Graves' disease and myasthenia gravis in which the pathogenic autoantibodies against cell-surface receptors can only be detected by assays which measure functional interactions with such receptors. PMID- 2223918 TI - Computerized EEG in schizophrenic patients. AB - We undertook a study of electroencephalograms (EEGs) in 30 right-handed, untreated patients (27.3 +/- 10.0 years; hebephrenic, 16; paranoid, 12; residual, 2) who fulfilled ICD-9 criteria for schizophrenia and compared them with sex- and age-matched controls by using the percentage of power in six EEG frequency bands calculated as a fraction of total power. T-statistic significance probability mapping (t-SPM) showed that, compared with normal controls, schizophrenics had more slow activity (delta, theta, and alpha 1) in the parieto-occipital regions, and more fast activity (beta 1) in the occipital regions. In contrast, alpha 2 activity decreased strikingly in the occipital regions and this decreased activity extended over much of the head. These findings were thought to indicate both cerebral hypofunction and excitability in acute untreated schizophrenia. PMID- 2223919 TI - Increased serum phospholipase A2 activity in schizophrenia: a replication study. AB - Phospholipase A2 (PLA2) is a key enzyme in the metabolism of phospholipids. Because a disordered phospholipid metabolism has frequently been reported in schizophrenia, we investigated the PLA2 activity in serum from 14 drug-free paranoid schizophrenic patients, 20 healthy controls, and 8 nonschizophrenic psychiatric patients. Schizophrenics showed significantly higher PLA2 activity than healthy controls and nonschizophrenic patients. The increment in schizophrenics was not due to increased concentration of pancreatic secretory PLA2, as concerning pancreatic PLA2 no differences were found among the 3 proband groups. The present findings confirm the results of our previous study and suggest that increased serum PLA2 activity might reflect an increment in the intracellular enzyme activity in schizophrenia. In the brain the activation of intracellular PLA2 results in changes in neuronal activity due to alterations in receptor sensitivity and in neurotransmitter metabolism. The possibility that such PLA2-induced mechanisms are involved in the pathogenesis of schizophrenia should be investigated in further experiments. PMID- 2223920 TI - Fluoxetine and neuroleptic malignant syndrome. AB - The authors present a case report of neuroleptic malignant syndrome (NMS) in a patient commencing treatment with fluoxetine alone who had previously been treated with several antipsychotic and antidepressant combinations. On reviewing the literature on the pathogenesis of NMS, the authors hypothesize a facilitative role of the neurotransmitter serotonin (5-HT) in conjunction with central dopaminergic blockade in the precipitation of NMS. PMID- 2223921 TI - Comparison of urinary-free cortisol in depressed and nondepressed patients with malignancy. PMID- 2223922 TI - The plasma tetrahydrobiopterin levels in patients with affective disorders. PMID- 2223923 TI - The influence of cigarette smoking on haloperidol pharmacokinetics. PMID- 2223924 TI - Abnormal plasma catecholamines in hyperkinetic children. PMID- 2223925 TI - EPS, NMS, and AIDS. PMID- 2223926 TI - Importance of treatment follow-up. PMID- 2223927 TI - Getting away with murder. PMID- 2223928 TI - Effects of daily oral m-chlorophenylpiperazine in elderly depressed patients. Initial experience with a serotonin agonist. AB - Six patients (mean age 62.5 +/- 7.6 years) with major depression were treated for 2 weeks with the serotonin agonist m-chlorophenylpiperazine (m-CPP), 80 mg/day in a double-blind, placebo-controlled, crossover-design pilot study. Two patients showed clinically significant improvement in depressive symptoms during active drug treatment, whereas two others showed modest effects. All patients tolerated the drug, with no major side effects and no changes in vital signs or in liver, renal, thyroid, or hematological function. Further studies are needed to determine the characteristics of the possible antidepressant effects of m-CPP; such work may yield greater understanding of the role of serotonin in affective and other psychiatric disorders. PMID- 2223929 TI - Elevated CSF protein in male patients with depression. AB - Elevation of total protein is the most frequent pathologic finding in the cerebrospinal fluid (CSF) examination. It occurs in a variety of situations, such as inflammation or tumors of the central nervous system (CNS), degenerative disorders, and subarachnoid hemorrhage, or as a result of traumatic taps. It has also been reported, for unknown reasons, in patients with psychiatric disease. In a study of hormone changes in depression, 9 of 24 (38%) patients (13 male, 11 female) were found to have elevated CSF protein levels (greater than 45 mg/dl), whereas no elevations were found in healthy controls (8 male, 9 female). Eight of the patients with the elevated CSF protein levels were male (62%) and one was female (9%). Depressed patients had significantly higher CSF protein levels (44.7 +/- 18.0 mg/dl) than controls (31.5 +/- 6.0 mg/dl) (t = 3.32, df = 30.37, p = 0.002). No relationship was found between CSF protein levels and (1) the use of medication (tricyclic antidepressants, lithium carbonate, or monoamine oxidase inhibitors) or (2) post-dexamethasone suppression test cortisol levels. Female controls, however, tended to have lower protein levels than male controls, whereas female patients had significantly lower levels than male patients. Protein electrophoresis was performed on 21 of the 41 subjects (13 patients, 8 controls). Male patients had nonsignificantly higher absolute concentrations of CSF albumin and the globulin fractions when compared to male controls. These differences in CSF protein do not suggest monoclonal CSF protein production, nor are they the result of this elevated peripheral protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2223930 TI - The plasma level of methylphenidate in the single-dose oral methylphenidate test. PMID- 2223931 TI - Platelet serotonin uptake in bulimia nervosa. PMID- 2223932 TI - The impact of increasing blood glucose on psychological functioning. AB - In the first experiment, after taking a drink containing either glucose or a placebo, subjects performed a task that involved watching a screen for 25 min, during which they had to press a space bar when one of four digits appeared. Over the duration of the task the performance of both groups improved, but in those taking the glucose drink the improvement occurred significantly earlier. In a second experiment subjects for 20 min performed a task requiring hand-eye coordination. The taking of a glucose-containing drink was not associated with a change in performance. A review of the relevant literature suggested that glucose is beneficial when performing tasks demanding little mental capacity. PMID- 2223933 TI - Precortical filtering and selective attention: an evoked potential analysis. AB - Attention-related changes in the human auditory brainstem response and the short latency somatosensory evoked potential (SLSEP) were demonstrated in separate experiments. In Experiment 1, ABRs were recorded during conditions in which subjects awaited the presentation of either auditory or somatosensory target stimuli. In Experiment 2, median nerve SLSEPs were recorded in a similar task context. Analyses of ABR and SLSEP component amplitudes and latencies revealed that the auditory nerve (wave II) and rostral brainstem (wave V) components of the ABR, and the cervical component (N12) of the SLSEP, were facilitated when attention was directed toward stimuli that were presented in the same sensory modality and receptive field as the EP-eliciting stimuli. These results suggest that central mechanisms can modulate the transmission of auditory and somatosensory information at an early, precortical stage and that these mechanisms play a role in auditory and somatosensory selective attention. PMID- 2223934 TI - Reflex modification in the electrodermal system: conceptual and methodological issues. AB - Reflex modification (RM) is the inhibition or facilitation of a reflex response by a stimulus (S1) occurring prior to a reflex-eliciting stimulus (S2). The present experiment investigated two issues: (1) whether RM may be confounded by orienting generated by changes in the experimental procedure, or habituation generated by repeated stimulus presentations; (2) whether the strength of RM is influenced by repeated pairing of S1 and S2, that is, classical conditioning. Two groups of subjects were given two series of stimulus presentations. Group A received first 10 S2-alone presentations, before 10 S1-S2 presentations. Group B received the stimuli in reversed order, that is, first 10 S1-S2 presentations, and then 10 S2-alone presentations. This design permits a comparison of unconfounded with confounded RM, as well as assessment of influences of learning. The results showed RM to be influenced by orienting caused by changes in the experimental procedure. The strength of RM tended to be gradually reduced as a function of the number of S1-S2 pairing, indicating that the orienting response to S1 habituated across trials. It is concluded that RM may be useful in the objective investigation of more complex cognitive processes. PMID- 2223935 TI - Effects of conditioned stimulus pre-exposure on human electrodermal conditioning to fear-relevant and fear-irrelevant stimuli. AB - The effects of conditioned stimulus (CS) pre-exposure and fear-relevance of the CS on human Pavlovian electrodermal conditioning were investigated. A differential delayed conditioning paradigm was used with a CS-unconditioned stimulus (US; shock) interval of 8 s. In Experiment 1, 64 subjects were randomized into four groups, two of which received fear-relevant stimuli and the other two fear-irrelevant stimuli. Half of the subjects were pre-exposed to the to-be-CSs and the other half to two not-to-be-CSs, with 15 exposure of each stimulus. During acquisition, subjects received 8 reinforced and 8 nonreinforced CS+ and CS- trials, and during the extinction phase 15 nonreinforced trials of each CS. Pre-exposure to the to-be-CSs retarded conditioning for the first and second interval anticipatory responses (FIRs and SIRs); that is, a latent inhibition effect was demonstrated, although the results for the FIR were inconclusive. The expected effects of fear-relevance were not revealed. Experiment 2 addressed the question whether the long pre-exposure period interfered with the frequently observed "preparedness effect" of higher resistance to extinction to fear-relevant stimuli. The design was similar to that of Experiment 1, but for half of the subjects the acquisition phase was initiated immediately after a short rest period, and for the other half acquisition started after an extended rest period, equal to the duration of the pre-exposure phase in Experiment 1. Twenty extinction trials of each CS were presented. A reliable difference in arousal in terms of spontaneous fluctuations was produced by the rest periods, but although differential conditioning was observed, no effect of fear-relevance was seen during extinction. PMID- 2223936 TI - Behavioral responsiveness in sleeping older adults. AB - The control of behavior by stimuli presented during sleep, and related effects on sleep and daytime sleepiness, were investigated in 17 older (age = 60-74 years) adults. Experimental subjects (N = 8) were trained while awake to terminate tone presentations by taking a deep breath. Tones were then presented following sleep onset for four consecutive nights with a mean intertone interval of 4 min. Control subjects (N = 9) slept in the laboratory but did not receive tones. The daytime sleepiness of both groups was assessed by recording latency to sleep onset in a morning and afternoon nap test. It was found that the experimental subjects responded reliably to the tones. Responding, however, was almost invariably accompanied by disruption of sleep and overall sleep structure was markedly altered. Surprisingly, the daytime sleepiness of experimental subjects was not reliably greater than that of control subjects. PMID- 2223937 TI - ERPs during continuous recognition memory for words. AB - Event-related brain potentials (ERPs) were recorded from 10 young adults during a version of the continuous recognition memory paradigm. Words were presented after lags of either 2, 8 or 32 intervening items (equiprobable) following their first presentation, and subjects were required on each trial to make a choice: new (never presented previously) or old (previously presented) response. To assess the effect of probability of new to old items, words were presented in separate blocks with ratios of new to old of 2:1 and 1:1. Reaction time increased and successful recognition decreased systematically as the lag between first and second presentations of an item increased, supporting the distinction between primary (immediate memory) and secondary memory for verbal material. However, there were no systematic effects of item lag on the ERP components. ERPs to new items were characterized by larger N300 and smaller P300 amplitudes (from about 250 to 700 ms) than those to old items. These amplitude differences between old and new ERPs were interpreted as primarily reflecting repetition as opposed to semantic priming effects. These old/new effects did not interact with probability, suggesting that frequency of occurrence is not a major determinant the ERP old/new difference. Old items elicited a late negativity following the behavioral response that was interpreted as due to the presence of a "positive slow wave," with a frontally oriented distribution to new words that was absent in the ERPs to old words. Similarly, subtraction of ERPs elicited by new items that were subsequently unrecognized from those subsequently recognized, showed that underlying the ERP subsequent "memory effect" was a "frontal positive slow wave," dissociable from P300 on the basis of differences in scalp distribution. Since positive slow wave has been interpreted as reflecting "further processing," the data suggest that such processing, possibly similar to elaboration (Graf & Mandler, 1984), enhanced the probability of subsequent recognition. PMID- 2223938 TI - [Laser spectroscopic assessment of induced hyperoxia--an animal experiment in lambs]. AB - The noninvasive determination of biochemical parameters has become an important aspect of intensive care medicine. The newly developed monitors for laser reflectometry provide the possibility of spectroscopic monitoring. The equipment consists of a near-infrared data collection unit and a personal computer. The four laser diodes emit light at wavelengths of 775, 805, 845 and 904 nm. By analyzing the changes in optical density during laser irradiation of biological tissue, information is obtained about the relative changes in the concentration of hemoglobin and the blood volume. In animal experiments with ten fetal lambs we evaluated the reliability of near infrared laser spectroscopy. Fetal hyperoxia was achieved by means of an extracorporeal circuit with interposition of a membrane oxygenator (0.8 m2, Scimed). During the induced hyperoxia the laser spectroscopic tracings showed a rise in the HbO2 signal with a synchronous decrease in the HbR signal. Additionally, the spectroscopic pattern showed a characteristic initial rise in the intracerebral blood volume, which stabilized after 4 minutes. We found a significant correlation between the intermittently measured PO2 values of the arterial blood samples and the laser spectroscopic HbO2 and HbR signals (r = 0.87, and r = -0.82, respectively; p less than 0.001). Furthermore, hyperoxia was indicated by the laser system with a short lag time. We conclude that laser spectroscopy is a reliable method with a high potential for clinical routine use in intensive care, as it provides noninvasive continuous information at comparatively low costs using portable monitors. PMID- 2223939 TI - Broadband method for measuring the ultrasonic absorption spectrum of biological tissues. AB - An apparatus is described which in the frequency range from about 5 to 500 MHz allows the ultrasonic absorption coefficient of biological tissues to be measured with 1% accuracy. This apparatus is based on a pulse transmission method in which a computer-controlled mode of operation is combined with a RF substitution technique. Superheterodyne detection of the transmitted signal, multiple data recording and signal averaging result in a high sensitivity of the measuring method. The apparatus can be also used to analyze the ultrasonic pulse reflected by the sample. PMID- 2223941 TI - [Determination of standards for hydroxyapatite as bone substitute]. AB - Hydroxyapatite ceramic for surgical implants is a material that meets the ASTM F 1185-88 standard. A standard defines specifications for the manufacturer, in particular in the area of quality control. A standard like this provides the necessary basis for clinical use, but only the approval of the public health department provides a fully adequate basis for broader application. PMID- 2223942 TI - [Lectures of the 15th annual meeting of the Austrian Society for Biomedical Techniques. Innsbruck, June 7-9, 1990. Proceedings]. PMID- 2223940 TI - [Error analysis, biological modification factors and variance of peri-ungual video-capillary microscopy]. AB - Error analysis or the evaluation of the precision of microscopic measurements must distinguish between technical errors inherent in the measuring system, and biological variability. The technical error inherent in the overall system in the case of linear measurements is smaller than the lengths to be measured by 1 or 2 orders of magnitude. Thus, the erythrocyte column lengths can be correctly, reproducibly and linearly quantified over the entire measuring range. The biological influencing factors can largely be taken into account or excluded by suitable standardisation of the measuring process. Despite a considerable individual fluctuation in the erythrocyte velocity, there is, on average, no significant dependence of the measuring parameter within the daily profile or from day to day. Differences in capillary perfusion in the presence of diseases associated with microcirculatory disorders or a therapeutic influence on erythrocyte velocity can thus be reliably demonstrated. PMID- 2223943 TI - [Thin-film electrodes for medical diagnosis]. PMID- 2223944 TI - [pH-ISFETs--technical recording aspects in relation to clinical use]. PMID- 2223945 TI - [Regional resolution power of pulsed Doppler ultrasound as a function of signal amplitude]. PMID- 2223946 TI - [Analysis and modeling of backscattering from ultrasound signals for tissue characterization]. PMID- 2223947 TI - [Doppler ultrasound detection of thrombocyte aggregation]. PMID- 2223948 TI - [Effect of high frequency spin resonance on image production in nuclear magnetic resonance tomography]. PMID- 2223949 TI - [Image communication and image storage in the hospital]. PMID- 2223950 TI - [Visual aspects of the man-machine interface]. PMID- 2223951 TI - [Development of new biosensors in blood analysis]. PMID- 2223952 TI - [Electrochemical glucose sensors with selectively permeable polypyrrole membranes for suppressing artifacts]. PMID- 2223953 TI - [Electrocatalytic glucose sensor for subcutaneous application]. PMID- 2223954 TI - [A new type of magnetic position sensor]. PMID- 2223955 TI - [New optoelectronic sensors for measuring pulse]. PMID- 2223956 TI - [Determination of the force system of fixed orthodontic appliances]. PMID- 2223957 TI - [Treatment of spinal and supraspinal spasticity by intrathecal administration of baclofen using a computer-assisted pump system]. PMID- 2223958 TI - [24-hour pH measurement in ulcer patients]. PMID- 2223959 TI - [Development of a modified galvanic probe for treatment of esophageal varices]. PMID- 2223960 TI - [Implantable neurostimulator with programmable logic]. PMID- 2223961 TI - [The problem area of biological effects of technical electromagnetic energy fields]. PMID- 2223962 TI - [The class E concept as a principle for efficient transcutaneous signal and power transmission]. PMID- 2223963 TI - [Diaphragm-synchronous functional stimulation of the glottis]. PMID- 2223964 TI - [Respiration-synchronous bilateral direct electric posticus stimulation in animal experiments]. PMID- 2223965 TI - [Optimizing high frequency data and energy transmission for electrostimulation implants]. PMID- 2223966 TI - [Chronic electrostimulation: effects on the morphology of the nerve]. PMID- 2223967 TI - [Impulse pattern in the auditory nerve in speech-coded electric stimulation of the cochlea]. PMID- 2223968 TI - [Prototype of an HDO speech processor for the Vienna auditory prosthesis--results of a comparative clinical study with a conventional and HDO speech processor in patients with the Vienna auditory prosthesis]. PMID- 2223969 TI - [CAP--a new cochlear implant system for combined analog and pulsatile electrostimulation of the auditory nerve]. PMID- 2223970 TI - [Value of 3-D reconstruction in CT of the shoulder]. PMID- 2223972 TI - [Use of a personal computer for digital image processing in radiotherapy]. PMID- 2223971 TI - [Functional disorders of cardiac pacemakers caused by irradiation with a linear accelerator and telecobalt equipment]. PMID- 2223973 TI - [Use of 1H-31P magnetic resonance spectroscopy for evaluating growth of tumors in the area of the head]. PMID- 2223974 TI - [Calculation and graphic presentation of the Kaplan-Meier product moment correlation using the personal computer program KAPLGRAPH]. PMID- 2223975 TI - [Electronic axiography of temporomandibular joint fractures for directing physical therapy]. PMID- 2223976 TI - [Effect of static magnetic fields on biosignal processing in humans]. PMID- 2223977 TI - [3-dimensional movement analysis as a clinical method of objective assessment of lameness in the horse]. PMID- 2223978 TI - [Concomitant monitoring of glucose-dependent variables]. PMID- 2223979 TI - [Complex processing of sensor values]. PMID- 2223980 TI - [Autonomous monitoring with the personal computer-assessment]. PMID- 2223982 TI - [Development of a medical information and documentation system for surgery]. PMID- 2223981 TI - [System for documenting and optimizing metabolic control in type I diabetes mellitus]. PMID- 2223983 TI - [Computer-assisted expert evaluation of the motor system]. PMID- 2223984 TI - [Medical image processing using a personal computer; digital bone density measurement with a new non-invasive procedure]. PMID- 2223986 TI - [The TFS system: a system for testing, fitting and speech processing for the Vienna cochlear implants]. PMID- 2223985 TI - [Use of digital signal processing in medical technique exemplified by audiologic measurements]. PMID- 2223987 TI - [Non-invasive determination of the anaerobic threshold]. PMID- 2223988 TI - [Use of simple mathematical models in sports medicine performance diagnosis]. PMID- 2223989 TI - [Eccentric load on leg extensor muscles in exactly defined biomechanical conditions]. PMID- 2223990 TI - [MRT--detection of muscle changes following physical stress]. PMID- 2223991 TI - [Presentation of a mixed local area network with Apple Macintosh computers, MS Dos compatible PC's and/or a Sun workstation]. PMID- 2223992 TI - [Wheelchair ergometry: technical principles and practical applications]. PMID- 2223993 TI - [Measuring plasma membrane viscosity on-line using flow cytometry]. PMID- 2223995 TI - [Digital method for elimination of ECG artefacts in surface EMG]. PMID- 2223994 TI - [Need assessment for medical technical equipment in health facilities]. PMID- 2223996 TI - [Current supply for medical equipment with accumulators]. PMID- 2223997 TI - [Classification of injuries and severity of injuries in collision automobile accidents]. PMID- 2223998 TI - [Monitoring movement in sports medicine using amorphous ferromagnetic sensors]. PMID- 2223999 TI - [A 2-dimensional model of biological joints]. PMID- 2224000 TI - [Use of electronic axiography in diagnosis and therapy]. PMID- 2224001 TI - [Intra-articular pressure measurements of the elbow joint of the dog using a personal computer-assisted system]. PMID- 2224002 TI - [Cervicomotography]. PMID- 2224003 TI - The properties of deposited metal clusters generated by laser evaporation. AB - Metal clusters have been produced using a laser evaporation source. A Nd-YAG laser beam focused onto a solid silver rod was used to evaporate the material, which was then cooled to form clusters with the help of a pulsed high pressure He beam. TOF mass spectra of these clusters reveal a strong occurrence of small and medium sized clusters (n less than 100). Clusters were also deposited onto grid supported thin layers of carbon-films which were investigated by transmission electron microscopy. Very high resolution pictures of these grids were used to analyze the size distribution and the structure of the deposited clusters. The diffraction pattern caused by crystalline structure of the clusters reveal 3- and 5-fold symmetries besides the pattern reflecting the fcc bulk structure. This can be explained in terms of icosahedron and cuboctahedron type clusters deposited on the surface of the carbon layer. There is strong evidence that part of these cluster geometries had already been formed before the deposition process. The non linear dependence of the cluster size and the cluster density on the generating conditions is discussed. PMID- 2224004 TI - [Corrosion behavior of antithrombogenic coating of silicon carbide]. PMID- 2224005 TI - Microfabricated sensors for medical applications. PMID- 2224006 TI - [Biomaterial: cartilage--use in oromandibulofacial surgery]. PMID- 2224007 TI - [Determining vitality parameters of cartilage transplants using magnetic resonance spectroscopy]. PMID- 2224008 TI - [Biocompatible materials in middle ear surgery]. PMID- 2224009 TI - [A high resolution ECG mapping procedure for examinations during coronary dilatation]. PMID- 2224010 TI - Three dimensional localization of the pathological area in cerebro-vascular accidents with multichannel magnetoencephalography. PMID- 2224011 TI - [3-D postprocessing in magnetic resonance tomography]. PMID- 2224012 TI - [A new device for continuous ambulatory 24-h fractionated blood sampling]. PMID- 2224013 TI - [Endoscopic microsurgery--challenge for the surgeon, biomedical specialist and technician]. PMID- 2224014 TI - [Electrode forms for reducing tumor mass using high frequency current]. PMID- 2224015 TI - [Expert systems in medicine: attempt at assessing the consequences]. PMID- 2224016 TI - [Computer simulation of tachycardia in the human heart]. PMID- 2224017 TI - [Electrostimulation--medicine of the third millenium]. PMID- 2224018 TI - [Functional rehabilitation using technical aids--a new strategy for medical technicians]. PMID- 2224019 TI - [Sensors in medicine]. PMID- 2224020 TI - [The importance of microelectronics in implant technology]. PMID- 2224021 TI - [Technique of movement analysis--current aspects and future prospects]. PMID- 2224023 TI - [The future development of medical technique--trends and perspectives]. PMID- 2224022 TI - [New aspects of biomedical technique in sports medicine]. PMID- 2224024 TI - [Measuring microfluctuations of action potential propagation in heart tissue samples]. PMID- 2224025 TI - [Modeling cardiovascular flow with a technical model]. PMID- 2224026 TI - [Cardiomyoplasty--technique and initial animal experiment results]. PMID- 2224027 TI - [Non-invasive continuous monitoring of heart function using miniaturized scintillation detectors and attached computer system]. PMID- 2224028 TI - [Functional heart replacement with the screw-spindle pump--initial results]. PMID- 2224029 TI - [Effect of a static 0.2 Tesla magnetic field on somatosensory evoked potentials and the EEG arousal spectrum in periodic stimulation of the median nerve]. PMID- 2224030 TI - [Clinical experiences with applications of implantable systems for gait correction in patients with hemiparesis]. PMID- 2224031 TI - Correction of scoliosis by implantable electrical stimulator. AB - Intramuscular electrical muscle stimulation has been used to treat spinal curvature. Five single-channel implantable stimulators with two alternating outputs each output supplying electrical stimuli to one reference (+) and two active (-) platinum corkscrew electrodes inserted into the deep paraspinal musculature were implanted. Stimulation is applied daily during rest, and nightly, during sleep, through implanted electrodes, evoking muscle contractions which cause correction of the curvature. Arrest of rapid progression in five patients with single primary curve, treated up to almost four years, (44 months) was observed in 60%. In one case the implantable system was removed after 10 months of treatment. PMID- 2224032 TI - [The course of mobility with the 6-channel surface stimulation belt in rehabilitation of patients with paraplegia]. PMID- 2224033 TI - [Electrostimulation in neurology--what does direct muscle stimulation contribute in flaccid paralysis?]. PMID- 2224034 TI - [Restorative neurology of central nervous system lesions with supraspinal spasticity--results of epidural spinal electrostimulation]. PMID- 2224035 TI - [Analysis of the ECG in diagnosis of graft rejection following heart transplantation]. PMID- 2224037 TI - [Personal computer use in the medical office exemplified by evaluation of echocardiography]. PMID- 2224038 TI - [Programming language for programming an 8-channel FESE stimulator]. PMID- 2224036 TI - [Computer simulation of the cardiovascular system in mechanical heart assistance]. PMID- 2224039 TI - Application of computer techniques for the measurement of efficiency of patients with disfunction of motorial organs. PMID- 2224040 TI - [Microcomputer-assisted 64-channel EEG amplifier (DC-2kHz) with digital filter and 16 bit resolution]. PMID- 2224041 TI - [Simultaneous continuous EEG evoked potential monitoring using a personal computer]. PMID- 2224042 TI - Computer-based sleep monitoring in SIDS-risk infants--preliminary results. AB - A computerized, PC-based system is introduced for sleep monitoring in infants. The system is capable of digitizing and storing 22 physiological variables over a whole-night sleep period. The preprocessed data can be displayed on a single page; further processing can be done on the digitally stored data. PMID- 2224043 TI - [Microminiaturized multiple temperature sensor for measuring blood flow]. PMID- 2224044 TI - [Miniaturized pH sensors]. PMID- 2224045 TI - [Miniaturized electrode for measuring pH of the tooth surface]. PMID- 2224046 TI - Helix-coil stability constants for the naturally occurring amino acids in water. XXIII. Proline parameters from random poly (hydroxybutylglutamine-co-L-proline). AB - Water-soluble random copolymers containing L-proline and N5-(4-hydroxybutyl)-L glutamine were synthesized by copolymerization of the tripeptides H-L-Glu(OBzl)-L Glu(OBzl)-L-Glu(OBzl)-OH and H-L-Glu(OBzl)-L-Pro-L-Glu(OBzl)-OH, using benzotriazolyl-N-oxy-tris(dimethylamino)-phosphonium hexafluorophosphate as condensing reagent, and subsequent aminolysis of the Bzl ester groups with 4 amino-1-butanol. These copolymers were found to contain significant amounts of N5 (4-hydroxybutyl)-D-glutamine, thus requiring the synthesis of a binary copolymer containing only D- and L-N5-(4-hydroxybutyl)glutamine residues in order to evaluate the possible effects of the D-residues on the conformational properties of poly(hydroxybutylglutamine-co-L-proline). The different copolymers were fractionated, and their thermally induced helix-coil transition curves were obtained in water at neutral pH. When proper corrections were applied for the helix-destabilizing properties of N5-(4-hydroxybutyl)-D-glutamine, the Zimm-Bragg parameters sigma and s for L-proline could be deduced from the melting curves of poly(hydroxybutylglutamine-co-L-proline). The results indicate that L-proline acts as a very strong helix breaker over the entire temperature range from 0 to 60 degrees C. PMID- 2224047 TI - Polarized electronic spectra of Z-DNA single crystals. AB - Polarized electronic absorption spectra of the (100) face of single crystals of the Z-form double helical duplex of d(m5CGUAm5CG) have been obtained from Kramers Kronig analysis of reflection data. The c crystallographic axis is parallel to the helix axis and shows but weak absorption. The b axis is perpendicular to the helix axis and shows a structureless absorption band centered at 270 nm with an oscillator strength of 0.26. Calculations of the crystal spectra utilizing available transition moment data for the individual chromophores are carried through using the oriented gas model (no interbase interactions) and, again, employing all base-base interactions (point dipole) in the duplex. The calculated hypochromism of the 270 nm band is much less than the experimental value obtained from the crystal data. The crystal spectra appear to be representative of Z-form double helices of essentially infinite length and not of a collection of twelve base duplexes. No evidence for n pi* transitions polarized parallel to the helix axis is found. PMID- 2224049 TI - Stereochemical behavior of acyclic peptide-cation complexes. AB - The role of the beta-turns in the peptide interaction with several cations was investigated. In this work we report the solution studies of four linear peptides: Z-Aib-Aib-Aib-L-Val-OMe, Boc-D-aIle-L-Ile-D-aIle-L-Ile-OMe, Boc-L-Leu-L Leu-L-Leu-L-Leu-OMe, and Boc-L-Phe-D-Phe-L-Phe-D-Phe-OMe. CD and 1H-nmr spectra reveal the presence of multiple ion-bonding equilibria. The stoichiometry and binding constant of the four peptides in the presence of Ca2+ ions in acetonitrile solution has been determined. Variable-temperature nmr spectra in the absence and in the presence of a large excess of cation have shown that the complexation process is not critically dependent on the conformation of the free peptide. PMID- 2224048 TI - On the multiple-minima problem in the conformational analysis of polypeptides. IV. Application of the electrostatically driven Monte Carlo method to the 20 residue membrane-bound portion of melittin. AB - The conformational space of the membrane-bound portion of melittin has been searched using the electrostatically driven Monte Carlo (EDMC) method with the ECEPP/2 (empirical conformational energy program for peptides) algorithm. The former methodology assumes that a polypeptide or protein molecule is driven toward the native structure by the combined action of electrostatic interactions and stochastic conformational changes associated with thermal movements. The algorithm produces a Monte Carlo search in the conformational hyperspace of the polypeptide using electrostatic predictions and a random sampling technique, combined with local minimization of the energy function, to locate low-energy conformations. As a result of 8 test calculations on the 20-residue membrane bound portion of melittin, starting from six arbitrary and two completely random conformations, the method was able to locate a very low-energy region of the potential with a well-defined structure for the backbone. In all of the cases under study, the method found a cluster of similar low-energy conformations that agree well with the structure deduced from x-ray diffraction experiments and with one computed earlier by the build-up procedure. PMID- 2224050 TI - A new mechanism of mechanochemical coupling: stretch-induced increase in carboxyl pKa as a diagnostic. PMID- 2224051 TI - Phase transitions of concentrated DNA solutions in low concentrations of 1:1 supporting electrolyte. AB - Transitions between isotropic and liquid crystalline phases of concentrated solutions of DNA with an average contour length (500 A) near the persistence length were examined in 0.01 M supporting 1:1 electrolyte (predominantly NaCl). A quantitative phase diagram describing the transitions occurring over a DNA concentration range from 100 to 290 mg/mL and temperatures from 20 to 60 degrees C was constructed from solid-state 31P-nmr data and examination of the morphologies of the mesophases by polarized light microscopy. Three anisotropic phases were observed in solutions with DNA concentrations of 160-290 mg/mL: an unidentified, weakly birefringent phase termed "precholesteric," a true cholesteric phase with pitch approximately 2 microns, and a third, presumably more highly ordered phase. Comparison with previous studies showed that the critical concentration for anisotropic phase formation and the nature of the phases formed by these DNA molecules are not strongly affected by decreasing the supporting electrolyte concentration from approximately 0.2 M to 10 mM. There are, however, profound effects of decreasing the supporting electrolyte concentration on the width of the transition from isotropic to totally anisotropic solutions, and the nature of the transitions between phases. Decreasing the supporting electrolyte concentration significantly increases the concentration range of persistence of the isotrophic phase, and results in the formation of triphasic solutions (isotropic and two liquid crystalline phases). Values of the critical DNA concentrations for anisotropic phase formation from the theory of A. Stroobants et al. [(1986) Macromolecules 19, 2232 to 2238] were found to be significantly lower than the observed values for any reasonable estimate of the effective radius, probably because of the relatively short lengths of DNA fragments examined in the present study. Comparison of the experimentally determined DNA concentrations required for anisotropic phase formation with the values predicted from Flory's lattice statistics theory, which explicitly considers the rod length, permitted estimation of the effective DNA radius. The estimated radius was inconsistent with effective radii calculated from Poisson-Boltzmann (P-B) theory based on a supporting electrolyte concentration of 10 mM, but was in fair agreement with P-B theory assuming that Na+ DNA contributes approximately 0.24 Na+ counterions/nucleotide to the effective free sodium ion concentration. PMID- 2224053 TI - Peptide growth factors and cell cycle control. AB - Research on mammalian cell cycle control focuses on the points discussed below. Peptide growth factors are multifunctional regulators of growth and differentiation that act by autocrine and paracrine mechanisms. Gene transcription changes are key steps in the control of the G0 in equilibrium with G1----S transition of the cell cycle. Both peptide growth factors and classical tropic hormones, are capable of rapidly modulating transcription through the induction of genes (fos/jun) that encode nuclear transregulator proteins. PMID- 2224052 TI - Crystal structure and solution conformation of S,S'-bis(Boc-Cys-Ala-OMe): intramolecular antiparallel beta-sheet conformation of an acyclic cystine peptide. AB - The conformation of the acyclic biscystine peptide S,S'-bis(Boc-Cys-Ala-OMe) has been studied in the solid state by x-ray diffraction, and in solution by 1H- and 13C-nmr, ir, and CD methods. The peptide molecule has a twofold rotation symmetry and adopts an intramolecular antiparallel beta-sheet structure in the solid state. The two antiparallel extended strands are stabilized by two hydrogen bonds between the Boc CO and Ala NH groups [N...O 2.964 (3) A, O...HN 2.11 (3) A, and NH...O angle 162 (3) degrees]. The disulfide bridge has a right-handed conformation with the torsion angle C beta SSC beta = 95.8 (2) degrees. In solution the presence of a twofold rotation symmetry in the molecule is evident from the 1H- and 13C-nmr spectra. 1H-nmr studies, using solvent and temperature dependencies of NH chemical shifts, paramagnetic radical induced line broadening, and rate of deuterium-hydrogen exchange effects on NH resonances, suggest that Ala NH is solvent shielded and intramolecularly hydrogen bonded in CDCl3 and in (CD3)2SO. Nuclear Overhauser effects observed between Cys C alpha H and Ala NH protons and ir studies provide evidence of the occurrence of antiparallel beta sheet structure in these solvents. The CD spectra of the peptide in organic solvents are characteristic of those observed for cystine peptides that have been shown to adopt antiparallel beta-sheet structures. PMID- 2224054 TI - Microexplants of human thymus: how do the thymic epithelial cells react to lymphocyte death? AB - The early steps which follow the seeding in culture of human thymic tissue fragments are characterized by a rapid disappearance of lymphatic cells. Under these experimental conditions thymic epithelial cells (TECs) quickly modify their reticular arrangement, assuming an "islet" organization similar to those of epithelial parenchymatous organs. The cytoplasmic projections of TECs surrounding the few surviving thymocytes are lost. Further, the loss of TECs cytoplasmic organelles parallels the reduction of thymocytes, leading to an ultrastructural picture of "undifferentiated" epithelial cells. These findings favour the hypothesis of "one" thymic epithelial cell type, acting as a dynamic unit which adapts its cytological organization to microenvironmental conditions. Further, these observations contribute towards elucidating the reaction of TECs to a selective T-lymphocyte reduction, such as occurs in some human pathological conditions. PMID- 2224055 TI - Utilization of 2',3'-dideoxyguanosine 5'-triphosphate as an inhibitor and substrate for DNA polymerase alpha. AB - The activity of DNA polymerase alpha was strongly inhibited by low concentrations (less than 1 microM) of 2',3'-dideoxyguanosine 5'-triphosphate (ddGTP) in the presence of Mn2+, although the incorporation of [3H]ddGTP into the product DNA was not detectable under the same reaction conditions. ddGTP competitively inhibited the incorporation of [3H]dGTP into the DNA. The Kis of DNA polymerase alpha for ddGTP were as low as 0.035 microM with activated DNA and 0.044 microM with (dC)n.(dG)12-18 as respective template.primers. By increasing [3H]ddGTP concentration (greater than 1 microM), however, it became an efficient substrate for DNA polymerase alpha. Under the assay conditions with activated DNA as the template.primer and Mg2+ as the divalent cation, the maximum incorporation rate of [3H]ddGTP reached 14.5% when compared to that of the corresponding normal substrate [3H]dGTP. These results indicate that the observed inhibition of DNA polymerase alpha activity by low concentrations of ddGTP in the presence of Mn2+ cannot be explained by the incorporation of ddGTP followed by chain termination of the growing DNA, and the results also support the previously presented hypothesis that the inhibition is caused by competition between the dideoxynucleotide inhibitor and its corresponding deoxynucleotide substrate at the same enzyme binding site. Thus ddGTP acts as an inhibitor or a substrate for DNA polymerase alpha depending on its concentration and the species of divalent cation. Some of the kinetic properties of DNA polymerase alpha connected with ddGTP are also described. PMID- 2224056 TI - The gill lipids of spawning Pacific salmon. AB - The gill phospholipids of 2 Pacific salmon species, Oncorhynchus keta and O gorbuscha, were composed of 38-43% phosphatidylcholine (PC) and 19-22% phosphatidylethanolamine (PE). Ether phosphoglycerides constituted 4-8% of the total PC fraction and 37-51% of the PE fraction. No significant changes in gill phospholipids were observed between those of pre-spawning fish in sea water and those of spawned salmon in the river. Cholesterol, however, was higher in the latter (0.59% vs 0.38%). PMID- 2224057 TI - Colony promoting activity: differences from interleukin-3 and similarities to interleukin-6. AB - The supernatant of long-term bone marrow culture contains colony promoting activity (CPA) which does not have granulocyte-macrophage colony stimulating activity (CSF) but which enhances granulocyte-macrophage (GM) colony formation in the presence of CSF. CPA might consist of IL-3 or IL-3-like activity, since CPA stimulates proliferation and differentiation of more immature cells to CSF responding granulocytes-macrophage progenitors (GM-CFC), and since IL-3 also stimulates immature hemopoietic cells to proliferate and differentiate to functional blood cells. IL-1 and IL-6 are also known to enhance GM colony formation. One or both of these molecules can accordingly be another candidate for CPA. In the present study, GM-CSF activity of IL-3 was dependent on the batch of serum: it was negative in the presence of fetal calf serum, but positive in the presence of horse serum. In contrast, GM-CSF and CPA showed no such dependence on the batch of serum. The addition of IL-3 to GM colony assay system did not enhance but rather suppressed GM colony formation. The supernatant of long-term bone marrow culture which contains substantial levels of CPA did not stimulate proliferation of IL-3 dependent DA-1 cells, but facilitated the proliferation of IL-6 dependent, MH60.BSF2 cells. No detectable level of IL-1 activity was found in the supernatant. These results indicate that CPA is different from IL-1, IL-3 or GM-CSF, but similar to or the same as IL-6. PMID- 2224058 TI - Pathobiology of myelodysplastic syndromes. AB - The myelodysplastic/preleukemic syndromes represent unique clinical situations since patients with initially mild hemopoietic abnormalities can be singled out from those progressing into frank myeloid leukemia. Here we confront data focused on the identification of critical cellular, molecular biological, cytogenetic and physiological defects leading to leukemic progression. An increasing amount of data supports our earlier hypothesis according to which the impairment of an endogenous (intracellular) life-cycle suppressor gene-product, or functionally related regulatory genes, plays the decisive role in the course of disease progression. The identification of systemic as well as clonally transmissible defects have clinical importance since in some cases the therapeutic application of the appropriate physiological substances may result in long lasting hematological remission. PMID- 2224060 TI - Randomized controlled study of chemoimmunotherapy with bestatin of acute nonlymphocytic leukemia in adults. AB - A new immunomodulating agent, bestatin (INN: Ubenimex has low toxicity even after long-term oral administration and has significant modifications in immunological response. A cooperative randomized controlled study of bestatin immunotherapy in combination with remission maintenance chemotherapy for adult acute nonlymphocytic leukemia (ANLL) was performed. After induction of complete remission, patients were randomized to the bestatin group (30 mg/bw per os (po) daily) and the control group. The 101 eligible cases (bestatin: 48, control: 53) were analyzed; the bestatin group achieved longer remission than the control group and a statistically significant longer survival. Though this prolongation of remission was not significant in the bestatin group compared to the control group in the 15-49 yr age group, in the 50-65 yr age group it was significantly longer. Bestatin is shown to be a clinically useful drug for immunotherapy of adult ANLL, since it has prolonged survival and remission especially in elderly patients, with few side-effects. PMID- 2224059 TI - Hematopoietic and hematologic properties of bestatin in normal and cyclophosphamide myelosuppressed mice. AB - Bestatin is a potent inhibitor of aminopeptidase, an enzyme found in abundance in the membrane of monocytes and macrophages. Following binding of bestatin to cells in the histiocytic lineage, the production of colony stimulating activity is upregulated (both in vitro and in vivo) with subsequent increases in hematopoietic and hematologic parameters. We report that the frequency and absolute numbers of CFU-GM as well as entry of CFU-GM into S phase (a measure of progenitor cell activity) is upregulated by treatment of animals with bestatin. This results in an increase in bone marrow cellularity in cyclophosphamide suppressed mice and an increase in the absolute neutrophil count in normal and suppressed mice. The therapeutic application of this hematopoietic modulator has been demonstrated in combination cyclophosphamide and bestatin therapeutic protocols. Because this indication for bestatin has only recently been recognized, few clinical studies have been undertaken utilizing appropriate surrogates of hematopoietic activity. However, preliminary clinical evidence of hematopoietic activity by this non-toxic dipeptide, as reviewed here, suggests that this may be an appropriate strategy for the treatment of myelosuppressed patients. PMID- 2224062 TI - Heparin and atherosclerosis: an investigative report on the treatment of atherosclerosis. AB - Both animal and clinical evidence of the special role of long-term low-dose heparin as a preventative of atherosclerosis is presented. Some of the many beneficial effects of heparin aside from its anticoagulant capability are mentioned. Concern about hemorrhage and osteoporosis which can occur when taken in the usual anticoagulant doses does not apply to long-term administration of low-dose heparin. Taken by the intrapulmonary route using an ultrasonic nebulizer weekly or fortnightly, heparin is safe and assures patient compliance. Further clinical trials are strongly indicated. PMID- 2224061 TI - The biological approach to radioimmunoscintigraphy. AB - The authors have analysed the theoretical and clinical implications of a biological approach to radioimmunoscintigraphy (RIS), a new diagnostic technique based on the in vivo reaction between radiolabelled monoclonal antibodies and tumor-associated antigens expressed by the neoplastic cells. The assumption is that, as in all radioisotopic procedures, the radioimmunoscintigraphic image is the expression of differences in concentration (and not in density) between adjacent tissues. This "biological premise" is analysed to demonstrate a possible role of RIS not only in diagnosis but also in prognosis and therapy. A comparison with other imaging procedures and with histopathology, considered as the "gold standard" of the present-day morphological approach to diagnosis, is also discussed. Finally, biological premises, as well as the initial results and prospects regarding the use of high doses of radiolabelled monoclonal antibodies for therapeutic purposes are presented. PMID- 2224063 TI - Down-regulation of LAK cell-mediated cytotoxicity: cancer and ageing. AB - A comparative study was made of the generation of lymphokine-activated killer (LAK) cells in patients with melanoma and healthy donors of different age groups. Significant reduction of effector cell cytotoxicity in patients following 72 h culture with 1,000 U/ml or recombinant IL-2 (rIL-2) as well as a decreased ability to generate LAK cells in elderly individuals were shown to be correlated with suppressor cell activation in rIL-2 stimulated cell population. Suppressor effect depends on monocytes and T-lymphocytes: partial abolition of suppression in LAK cells was observed following removal of adherent cells or treatment with OKT8 monoclonal antibodies and complement. PMID- 2224064 TI - Effects of membrane lipid and fluidity modifications on HIV-1 infectibility of primate lymphocytes in vitro. AB - Although most non-human primates, except the chimpanzee and the gibbon in vivo are not infectible by HIV-1, lymphocytes of several of these species can be infected by HIV-1 in vitro. In order to investigate whether the in vitro infectibility of primate lymphocytes might be attributed to plasma membrane adaptation processes or to serum factors, we compared HIV-1 infectibility of cultivated peripheral blood lymphocytes of macaques and of baboons on day one and on day ten of cultivation. These data were correlated to plasma membrane lipid composition and membrane fluidity. We found a correlation between increased HIV-1 in vitro infectibility and changes in plasma membrane lipid composition resulting in decreased membrane fluidity of cultured primate lymphocytes. PMID- 2224065 TI - Protein kinase C and casein kinase II activities in two human colon carcinoma cell lines, HT-29 and CaCo-2: possible correlation with differentiation. AB - Protein kinase C (PK-C) and casein kinase II (CK-II) activities were studied in two human colon carcinoma cell lines (HT-29 and CaCO-2) undergoing differentiation in vitro resulting, in small-intestine-like cells. CaCo-2 cells, when grown under standard conditions, appear to undergo spontaneous differentiation. In these cells PK-C and CK-II activities were determined on day 5, 10 and 15. No significant differences in activities were seen either in PK-C or CK-II activity. HT-29 cells, when grown in glucose-free medium can be stimulated to undergo differentiation which is completed within 20 days. PK-C and CK-II activities were determined after 5, 10, 15, 20 and 25 days, respectively. PK-C activity rose from 7.9 +/- 3.5 pmole 32P/mg protein/min at day 5 to 37.5 +/- 14.8 pmole 32P/mg protein/min at day 20. After 25 days the activity was reduced to 20.0 +/- 7.8 pmole 32P/mg protein/min. CK-II activity did not change significantly during day 5 to 20, but on day 25 there was a significant decrease in CK-II activity from 94.9 +/- 6.4 pmole 32P/mg protein/min (day 20) to 62.6 +/- 3.9 pmole 32P/mg protein/min (day 25) p = 0.003. The results in this study indicate a role for PK-C and CK-II in cell growth and differentiation. PMID- 2224066 TI - Mevalonate-derived proteins in liver regeneration. AB - Sixteen hours after partial hepatectomy in the rat, the synthesis of mevalonate (MVA) is not committed to produce cholesterol and only partially utilized for dolichol formation. In order to investigate the fate of MVA in this replicative system, slices of the remaining liver were incubated with 5-3H-MVA. Labeled proteins from whole liver and purified nuclei were analyzed after extensive delipidation and separation by SDS-PAGE. Many MVA-derived proteins were identified at 16 hours, while only two labelled peptides were detectable at 24 hours. The radioactivity was localized in covalently bound lipid moieties. A highly labeled 26 kD peptide was detectable in the nucleus at 16 hours, suggesting its involvement in the cell cycle progression. PMID- 2224067 TI - Consequences for retinal growth when vision occurs in S2 space. AB - We postulate that the process of vision occurs in the S2 space. The retina is endowed with the topology of a part of a two-sphere S2, roughly, the topology of a hemisphere. There is a corresponding topology on the tectal surface, induced by the anatomy of the retino-tectal connections. Our analysis predicts the experimentally observed "near-neighbour" relationships between points in the visual field and their representation in the tectum. Further, in this context, topological arguments are presented to indicate that if the normal developing retinal disc in goldfish undergoes a process of deformation, a discontinuity is generated at the retinal surface. This discontinuity makes the differential patterns of the retinal and tectal tissues more compatible, and also enables the retina (which grows throughout the life of the animal) to conveniently connect to the tectum. PMID- 2224068 TI - Investigation of the conditions for oscillations in two-variable models of biological processes. AB - A procedure is presented for the direct determination of possible limit cycles that might occur in two-coupled differential equations that can arise in the modeling of certain biological phenomena. Mathematical expressions are given so that for a particular pair of differential equations the possible limit cycles, their parameters, and stability properties can be calculated by a purely algebraic process. Several examples are used to illustrate the procedure. PMID- 2224069 TI - Network study of integrated biochemical switching system. I: Connection of basic elements. AB - As a first step to network study, a series of integrated biochemical switching systems (prototype of artificial neuronic device) was assumed based on Rosen's work and on the results of our previous studies. The effects of an excitatory stimulus on the switching properties of the proposed system were examined using computer simulations. The results can be summarized as follows: (i) the number of excited elements in sequentially connected systems is proportionally related to the value of the excitatory stimulus; (ii) when the introduction of the excitatory stimulus is too late, it can no longer be transmitted to any elements; (iii) the excitatory stimulus (signal) is amplified to a certain limit and is attenuated during propagation; (iv) by assuming several excitatory stimuli and varying their frequencies, the so-called long-term potentiation phenomenon can be observed; (v) supposing reversible interactions between two elements, a continuous switching pattern of the output is observed. PMID- 2224070 TI - Sheathed nuclear division in primary spermatocytes of Orgyia antiqua (Lepidoptera, Insecta). AB - The restructuring of spermatocytes during the first meiotic division is examined in the moth Orgyia antiqua (Lymantriidae, Lepidoptera) using transmission electron microscopy. Particular emphasis was placed on the behaviour of the perispindle membrane system. These membranes develop from layers of smooth endoplasmic reticulum wrapped around the prophase I nucleus and are retained until early telophase I. The original nuclear envelope is dissolved in metaphase I. Polar fenestrae in the perispindle membrane stacks are filled with numerous irregular membrane elements. The formation of new nuclear envelopes around the daughter nuclei takes place inside the perispindle membrane system. Finally, the membrane stacks rupture concomitantly with spindle elongation in late telophase I. Thus, division of primary spermatocytes in Orgyia antiqua has a surprising degree of similarity with the so-called closed mitosis. This mode of division is typical for many protozoa, algae and fungi. In the pertinent cells, the original nuclear envelope persists around the spindle area during nuclear division. In order to distinguish the closed mitosis from the situation in Orgyia antiqua spermatocytes, the term 'sheathed nuclear division' is suggested for the latter. PMID- 2224071 TI - Protein phosphorylation: a motive force for adaptive evolution. AB - Spontaneity and diversity are the intrinsic properties of protein phosphorylation. They provide living systems with opportunities for polyvariant transformation of expressed genetic information and alteration of their energy metabolism under change of living conditions. Thus, protein phosphorylation can be regarded as a molecular mechanism for adaptation and selection of mutant proteins useful for the cell, i.e. a motive force for adaptive evolution. PMID- 2224073 TI - Detection of cancer predisposition: laboratory approaches. PMID- 2224072 TI - The geometry of evolution. AB - Some structures are more suitable for self-organization through the Darwin Wallace mechanism of variation and selection than others. Such evolutionary adaptability (or evolvability) can itself evolve through variation and selection, either by virtue of being associated with reliability and stability or by hitchhiking along with the advantageous traits whose appearance it facilitates. In order for a structure to evolve there must be a reasonable probability that genetic variation carries it from one adaptive peak to another; at the same time the structure should not be overly unstable to phenotypic perturbations, as this is incompatible with occupying a peak. Organizations that are complex in terms of numbers of components and interactions are more likely to meet the peak-climbing condition, but less likely to meet the stability condition. Biological structures that are characterized by a high degree of component redundancy and multiple weak interactions satisfy these conflicting pressures. PMID- 2224074 TI - Epidemiologic evidence of genetic susceptibility to cancer. PMID- 2224075 TI - Detection of cancer predisposition by hypervariable region analysis. PMID- 2224076 TI - The use of comparative mapping to identify loci involved in human carcinogenesis. PMID- 2224077 TI - Hereditary polymorphisms of human drug metabolizing enzymes and cancer susceptibility. PMID- 2224078 TI - Legal and ethical issues in the laboratory assessment of genetic susceptibility to cancer. PMID- 2224079 TI - Acetylation. AB - The human acetylation polymorphism has been known for more than three decades since its discovery during the metabolic investigation of the antituberculous hydrazine drug, isoniazid. The trait was originally known as the "isoniazid acetylation polymorphism" but is now usually abbreviated to the "acetylation polymorphism" because the acetylation of numerous hydrazine and arylamine drugs and other chemicals are subject to this trait. A. Individuals phenotype as "slow" acetylators, homozygous for the slow acetylator gene, or "rapid" acetylators either heterozygous or homozygous for the rapid acetylator gene. Differences in individual acetylating capacity are ascribed to differences in the activities of the arylamine acetylating enzymes (isozymic N-acetyltransferase variants) of the liver, intestinal mucosa and certain other tissues. The chromosomal locus of the human gene has not been determined, but linkage analysis in mice indicates that the N-acetyltransferase gene is closely linked to Esterase-1 on mouse chromosome 8. RECOMMENDATION: 1) That the chromosomal locus of the human acetylator gene(s) be determined. B. The acetylator phenotype is a lifelong, stable characteristic of the individual that can be determined by procedures using any of several test agents (eg, caffeine, isoniazid, sulfamethazine, sulfapyridine). All suitable test agents discriminate rapid and slow acetylator phenotypes, whereas caffeine enables homozygous and heterozygous rapid acetylators to be discriminated from each other and from slow acetylators. These procedures can be used with confidence to determine the acetylator status of healthy adults and children but caution is necessary in interpreting this information for infants, in altered physiologic states and in the presence of certain diseases and environmental substances. RECOMMENDATIONs: 1) That investigators should strongly consider the use of the caffeine test for acetylator phenotype determination in human epidemiologic studies of acetylation because of its advantages over other test agents that are available. 2) That efforts to determine the structure of the acetylator genes responsible for the human acetylator polymorphism, and to determine the genes responsible for the hereditary acetylator polymorphisms in animal models for the human trait be continued apace with efforts on the human system. 3) That an improved test to determine the acetylator status utilizing that information and current molecular biology approaches and techniques applied to tissues that are readily available in human subjects (eg, leukocytes) be developed at a high priority. C. The hereditary acetylator status of individuals provides valuable information about their therapeutic, pharmacologic and toxicologic responses and is a prognosticator of unusual susceptibility to toxicity from drugs widely used for the treatment of diverse diseases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2224080 TI - Fragile sites, genomic rearrangements and cancer predisposition. PMID- 2224081 TI - The chromosome-breakage syndromes: rare disorders that provide models for studying somatic mutation. PMID- 2224082 TI - [Electric activity of striated muscles of the cervical part of the rabbit esophagus under conditions of hunger, food intake and satiation]. AB - The experiments of free-moving rabbits have shown that the muscles of the proximal zone in the esophageal cervical part functions as the superior esophageal sphincter. In hunger stage the motor unit activity of the sphincter has regular low-amplitude discharge with monomodal distribution of interspike intervals. The process of food satisfaction leads to the appearance of burst-like unit activity with bimodal distribution of interspike intervals. During the food intake reorganization of the motor unit activity of the esophageal cervical part is manifested in characteristic patterns of interspike interval distribution. PMID- 2224083 TI - [Improvement of the morphometry method and its use in electron microscopic studies]. AB - The paper describes morphometric device for electron microscope. Using this gauge one can get morphometric data from the screen of the electron microscope. Perspectives of morphometric analysis of ultra-structures in the electron microscope are discussed. PMID- 2224084 TI - [Structural organization of the adrenal cortex in rats with different types of autonomic reactivity under standard conditions and after exposure to different altitudes]. AB - The structural organization of adrenal cortex has been studied in intact rats and after short-term hypoxia exposure on different altitudes (2, 6, 8, 11 km). Previously rats have been divided into 3 groups by adrenaline test for determining of vegetative reactivity type. It has been found that some histochemical and morphometric indices of adrenal cortex had peculiarities with respect to type of vegetative reactivity (width of zones, their ratio, nuclear diameter, ascorbic acid content and its distribution and other) in intact rats. Under altitude these differences form individual character of steroidogenesis and determine resistance and reactivity of organism. PMID- 2224085 TI - [Effects of extracts of different parts of the brain of kindled animals on seizure activity of recipient rats]. AB - The peptide-containing fraction was emitted from the hippocampal and ventral mesencephalic region tissue of rats kindled with subconvulsant doses of corazol. Extracts were prepared by the help of hot acetic acid on the stage of generalized clonic-tonic seizure development. The intraventricular injection of VMR-extracts in relatively high dose increased seizure reactions which were induced in intact recipient rats by intraperitoneal corazol injection. The intraventricular injection of the extract in relatively low dose (100 times less) suppressed corazol-induced seizures in recipients. Data are discussed from the point of view of pathological epileptic system formation and the role played by peptides in supporting it's activity during pharmacological kindling. PMID- 2224086 TI - [Impulsive neuron activity of several structures of the brain after administration of benzene and its homologues]. AB - The obtained findings have shown that dominating inter-impulse intervals in the area of 1000 and more ms, and multimodality of their distribution occur in benzene, toluol, xylol injection within time-structure of some neurons activity of sensomotor cortex, hippocampus, thalamus and lateral hypothalamus. The particularities of neuronal activity of the studied structures were revealed by the injection of chemical substances in natural and artificially produced food motivation. The mechanism of neurons activity blockade in benzene and its homologous injection was suggested to be linked with their influence upon mediator process, and perhaps, peptide factors participating in the formation of neuronal activity. PMID- 2224087 TI - [Preliminary administration of perfluorocarbon emulsion: a new method of myocardial protection against ischemia]. AB - The study was conducted to determine if myocardium can be protected against ischemic and reperfusion damage by means of the preliminarily injected perfluorocarbon emulsion. Injection of the emulsion into rabbit 1, 12, 24 h prior to ischemia was found to decrease the extent of ischemic and reperfusion damage to myocardium. The cardiotropic effect of the injected emulsion is shown to be dose- and time dependent. PMID- 2224088 TI - [Oxygen consumption in the lungs of dogs with external hemorrhage and after reinfusion of blood]. AB - In experiments on 10 dogs with external blood loss and reinfusion it was demonstrated, that in hemorrhagic and posthemorrhagic periods oxygen consumption by the organism is determined not only by O2 demands of the large circulation tissues, but to a great extent by demands in O2 in the system of lesser circulation, what is being evidenced by activation of the metabolic function of the lungs. It turned out that in pathogenesis of postinfusion respiratory insufficiency reactions of lipid oxidation in the lungs play a significant role. PMID- 2224089 TI - [Restriction of functional disorders by the use of a regulatory peptide dalargin in burned rats infected with Staphylococcus aureus]. PMID- 2224090 TI - [Index of microcirculatory changes in experimental dehydration in animals]. AB - On the basis of morphokinetic synthesis principles the method of determination of summarizing criterion of microcirculatory system changes was developed. It consists of marked characteristics of changes of a number of the most important morphofunctional phenomena of each of this system compartments -- interstitial, lymphatic, blood and cellular -- with their successive summation to obtain the systemic microcirculation index. The experimental dehydration in rats being a model has shown that systemic microcirculatory index was 2 times as large in 3 days of dehydration, more than 3 times -- in 6 days, and 4, 5 times -- in 12 days. In the initial stage of the experiments maximal changes were found in interstitial compartment of the microcirculatory system. The intermediate period of dehydration differed by predominant changes of vascular compartment when the lymphatic phenomena were more evident than the hemomicrocirculatory ones. In the later stage of dehydration the cellular component changes of tissues and organs were predominant. PMID- 2224091 TI - [Role of bone marrow glycosaminoglycans in the reaction of the hematopoietic tissue to extreme conditions]. AB - The authors studied medullary glucosaminoglycans of rats and mice in extreme effects (hypoxia, hyperbaric oxygenation, inflammation, radiation, cooling, hemorrhage). Four types of reaction were determined which cause different changes of proliferation of hematopoietic cells. Hematopoiesis stimulation is accompanied by regular change of types of reaction of hematopoietic microenvironment. Its disturbance affects the changes of hematopoiesis and blood regeneration rate. It was shown that the increase of neutral glucosaminoglycans concentrations in bone marrow depended on the play ground and proliferative activity of erythroid sprout and that of acid glucosaminoglycans--primarily of granulocytic sprout. PMID- 2224092 TI - [Angiotensin mechanism of auriculo-acupuncture dental analgesia]. AB - In unanaesthetized rabbits auriculo-acupuncture electrostimulation with frequency of 15 Hz decreased the amplitude of somatosensory EP second component in response to the tooth pulp electrostimulation which was blocked by intravenous injection of naloxone but not by intraventricular injection of saralasin. The same effect of auriculo-acupuncture electrostimulation with frequency 100 Hz was blocked by saralasin, was increased by angiotensin II, was diminished by methysergide but wasn't changed by naloxone. It's suggested that there is angiotensinergic antinociceptive mechanism of dental pain which is activated by auriculo acupuncture electrostimulation with frequency 100 Hz. PMID- 2224093 TI - [Possibilities of enteral correction of posthemorrhagic disorders depending on the absorption function of the small intestine]. AB - Physiologic and morphologic research on animals in chronic experiment shows that depression of small intestine absorption function takes place during the first hour after hemorrhage of 30-40 ml/kg for 30-50% of animals and after hemorrhage of 50 ml/kg for 100% animals. This excludes except the possibility of efficient post-hemorrhage hypovolemia enteral correction without additional treatment. Enteral correction appears to be sufficient to preserve animal's life, being applied in 30 minutes after the hemorrhage of 30-40 ml/kg or in 90 minutes after the hemorrhage of 20 ml/kg. PMID- 2224094 TI - [Aggregates of modified low density lipoproteins indicate accumulation of lipids in human aortic intima cells in vitro]. AB - Spontaneous aggregation of glycosylated, desialated, oxidized and malondialdehyde modified low density lipoprotein (LDL) as well as LDL of coronary heart disease patients has been discovered using methods for determination of light transmission fluctuations in suspensions and gel filtration. At the same time; LDL of healthy donors failed to aggregate under conditions of cellular culture. On the other hand, human aortic cells from unaffected intima incubated with modified LDL, but not native LDL of healthy donors, showed a rise in esterified cholesterol levels. There was a strong correlation between the degree of LDL aggregation and intracellular cholesterol ester accumulation (r-0.86, p 0.001, n 21). Removal of aggregates by passing preparations through and 0.1 um filter significantly inhibited the accumulation of cholesterol esters. The obtained data point to the essential, if not decisive, role of LDL aggregation in the processes of lipid accumulation by intimal cells in vitro. PMID- 2224095 TI - [Metabolic pool of purine compounds in erythrocytes of mice during growth of transplanted tumors]. AB - The pattern of purine derivatives was studied in the erythrocytes of C3HA and ICR mice during Hepatoma 22 and Ehrlich ascites tumor cells growth. Host erythrocytes purine nucleotides, nucleosides and bases were affected by the implanted tumors. The results indicated that the host erythrocytes markedly concentrated adenine and guanine nucleotides on the 5th and 11th-12th day of tumor growth. By contrast, content of nucleosides and bases were sharply decreased during the log growth phase (5th day) with the restoring of these precursors within the 11th 12th day (plateau phase). These observations indicate that aspects of the purine compounds metabolism in host erythrocytes are linked with tumor development. PMID- 2224096 TI - [Effects of protamine on blood lipoproteins in the early period of hypercholesterolemia in rabbits]. AB - The content of protein, cholesterol and triglycerides in chylomicrons and different classes of blood serum lipoproteins was studied under protamine action in early (1 month) hypercholesterolemia. Except the low density lipoproteins the amount of triglycerides in the particles studied was practically unchanged. The content of proteins in all classes of lipoproteins was greatly increased and this may indicate that protamine activates the blood lipoprotein system. The enrichment of lipoproteins with cholesterol may be taken as being a result of protamine action in early hypercholesterolemia. The peculiar feature in the effect of protamine on mentioned lipoprotein components was that the protein/cholesterol ratio didn't change in chylomicrons, decreased in very low density lipoproteins and low density lipoproteins and increased in high density lipoproteins as compared with controls. PMID- 2224097 TI - [Heparin-sepharose affinity chromatography and reduction conditions as a method of a selective process for separate isoforms of apolipoprotein A]. AB - Gel permeation chromatography of VLDL apoproteins on Sepharose CL-6B in denaturing conditions and affinity chromatography on heparin-sepharose 4B in the presence of reducing agent dithiothreitol were used for preparative isolation of apolipoprotein E of high purity from human plasma VLDL. Sequential elution of apolipoprotein E from affinity column using increasing ionic strength solutions (0.4 M NaCl and 1.0 M NaCl) permitted to obtain "high affinity" apo E preparation with increased relative apoprotein isoform content with the highest positive charge. PMID- 2224098 TI - [Modeling of damage to cell membranes during photodynamic therapy: photosensitization of planar lipid bilayers by hematoporphyrin dimethyl ether]. AB - The variations of electrical conductance of planar bilayer lipid membranes (BLM) sensitized by hematoporphyrin dimethyl ether under visible light illumination were studied. The conductance of BLM does not change for some period after switching on the light, then an increase in the conductance starts and the membrane breaks. This "induction" time does not depend on addition of azide or ferricyanide to the solution, on addition of BHT to the lipid and on substitution of air for argon in the cell. The induction time for any new BLM, formed in the same cell immediately after the previous membrane was broken, is shorter. The variation of BLM boundary potentials during induction time was not observed. The results obtained suggest that the photodamage of BLM sensitized by HPD leads to accumulation of uncharged reaction products and oxygen does not take part in this process. PMID- 2224099 TI - [Detection of protease specifically splitting actin in revertants of Shigella flexneri L-forms]. AB - Proteolytic activity of cell extracts from revertants of Shigella flexneri L forms as well as biochemical properties of these strains and their sensitivity to antibiotics were studied. The protease found earlier in cells of strain E. coli A2 was shown to be synthesized by one of 8 revertants under study. This protease split actin and did not split some other proteins, its activity was inhibited by inhibitors of metalloproteases. Strain 5a2c which produced the protease was similar to the strain E. coli A2 and differed from other revertants in some biochemical properties, resistance to ampicillin and sensitivity to furazolidone. Thus the protease activity can be a marker of structural and functional transformation of Sh. flexneri under the influence of furazolidone. PMID- 2224101 TI - [Antiradical activity of retinal lipids under illumination]. AB - Antiradical activity (ARA) of lipids from cattle in norm and under strong illumination with and without antioxidants was studied by chemoluminiscence method of initiated ethylbenzol oxidation. Lipids ARA from the retina in norm was established to be sufficiently high-3.0 X 10(6) l/mol. s. alpha-tocopherol was proposed to be the main component influencing lipids ARA. Under strong illumination (15 min:, 0.8 J/s) lipids ARA decreased due to intensification of lipid peroxidation (the content of MDA was increased). The antioxidants (alpha tocopherol, potassium phenozan, ionol) in 0.1 mM concentrations increased the ARA of lipids in spite of light action. Changes in overall inhibitory activity of natural antioxidants and MDA content was antibat. PMID- 2224100 TI - [Comparative characterization of reactions of skeletal muscle arterial and venous vessels to combined adrenergic effects]. AB - In experiments with the constant blood flow perfusion of the cat calf muscle and combined actions of adrenalin and noradrenaline were tested as to the blood flow resistance changes of the arterial and venous blood vessels. Separately applied the catecholamines evoked vascular resistance changes practically similar in value; combined effects of catecholamines realized in greater increase of arterial than venous resistance. In contrast to arterial vessels supramaximal stimuli resulted in much lesser constrictive effect as compared with reaction of intramural veins to separately applied catecholamines. Greater doses of catecholamines being combined, stability of effector system of skeletal muscle veins is decreased as compared to arteries. PMID- 2224102 TI - [Restoration by T-activin and its subfractions of splenocyte membrane structures in thymectomized animals]. AB - It was shown that thymectomy induces the injury of plasma membranes of mouse splenocytes. This membrane disorders completely inhibit T-cell response on Concanavalin. A. The incubation of splenocytes with Tactivin or injection of Tactivin or its subfractions to the animals restore the membrane structure and T cell response. PMID- 2224103 TI - [Effects of desoxycorticosterone on 5-nucleotidase and adenosine deaminase activity in the hypothalamus and hippocampus of the rat brain]. AB - Influence of single (enzyme activities was determined 5h after the preparation) and multiple (for 7 days) DOCA administration on 5'-nucleotidase (EC 3.1.3.5) and adenosine deaminase (ES 3.5.4.4) activities in homogenate and subcellular fractions of the hypothalamus and hippocampus of the rat brain has been studied. It has been shown that DOCA enhances adenosine metabolism in the hypothalamus activating both the enzymes while in the hippocampus 5'-nucleotidase activity increases whereas adenosine deaminase activity decreases. Possible ways of mineralocorticoid effects on adenosine system and the role of this nucleoside in these hormones mechanism of action on CNS functional activity are being discussed. PMID- 2224104 TI - [Molecular-biochemical mechanisms of the effects of nootropic agents]. AB - It is a known fact that prophylactic hypodermic injection of non-typical lithonite tranquillizer in the day's dose of 30 mg/kg during 10 days prevents the exhaustion of antioxidant system of the body, normalizes qualitative and quantitative correlation of separate fractions of phospholipids, stabilizes the permeability of erythrocytic membranes and prevents the development of hypercholesterolemia of the stress. It is concluded that the lithonite's stress protecting effect is the result of its membrane stabilizing influence. PMID- 2224105 TI - [Antihypoxic effects of quinones connected with restoration of electro-transport and function of the respiratory chain of the isolated rat heart]. AB - The effect of hypoxia of middle severity (H50) has been investigated on the contractile activity, oxidative metabolism and bioenergetic function of the myocardium in the isolated rat heart. It has been shown that differences in the functional-metabolic parameters sensitivity in the resistant and non-resistant to hypoxia animals are defined by the primary utilization of different pathways of substrates oxidation--the succinate-oxidative pathway of oxidation or the NADH oxidative pathway, correspondingly. It is possible to correct the early hypoxic injuries of the electron-transfer function of the myocardium respiratory chain at the NADH-CoQ region (the first enzyme complex) with the help of quinones (vitamin K3, hydroquinone). The mechanism of this correction depends on the donor-acceptor properties of these compounds and it is the same both in the myocardium of the isolated heart and in the isolated mitochondria. Vitamin K3 is recommended to be utilized on the early stages of hypoxic injuries in myocardium as an antihypoxant of the energized type. PMID- 2224106 TI - [Molecular mechanisms of the membrane-protective effect of litonit in chronic stress]. AB - It is confirmed that prophylactic use of Pyracetam (500 mg/kg), Pikamilon (10 mg/kg) and new product of GABA B-44 (30 mg/kg) for 10-days in the conditions of chronic stress normalizes the activity of the key enzymes of antiradical defence and the content of lipid peroxides, warns the decrement of phospholipids and the changes in its qualitative ratio, prevents multidirectional changes in the activity of ferments-markers in the membrane of the brain and erythrocytes. It is concluded that nootropic agents give membrane stabilizing effects. PMID- 2224107 TI - [Changes in the level of dopamine and its metabolites in brain structures and immunocompetent organs in the formation of immune response]. AB - By the method of liquid chromatography with electrochemical detection dopamine level increase was shown within 2 min after immunization of rats with sheep red blood cells in n. caudatus. In 20 min after the immune response the acceleration of dopamine metabolism was observed in nuclei A9, A10, A11, accumbens, in amygdala, hypothalamus and hippocampus. In immunocompetent organs dopamine level was changed in 24 h after the immunization. PMID- 2224108 TI - [Axial shift of erythrocytes in arteries supplying blood to the cerebral cortex]. AB - In experiments with rabbits the widths of the axial flows of erythrocytes and of the parietal plasma layers were assessed in pial arterial ramifications supplying the cerebral cortex after their in vivo and in situ fixation under conditions of control and vasodilatation. A strict proportional relationship was revealed between the width of red cell flows and the diameter of pial arteries of 15-200 microns wide. However, the relative plasma volume in the microvessels below 50 microns in diameter was comparatively greater than in the larger vessels. The obtained results prove the feasibility of assessing the microvessels' diameters in tissues where one can see the red cell flow but the vascular walls are invisible. One of the reasons for the lower hematocrit in smaller blood vessels as compared to the larger ones was also elucidated. PMID- 2224109 TI - [Use of plasma clot in the evaluation of fibroblast progenitor cells of human bone marrow]. AB - Cultivation of human bone marrow cells in plasma clot resulted in high efficiency of cloning. It probably results from additional thrombin stimulus on fibroblast cell proliferation. Another cause of high cloning efficiency is independent of adherence to culture flask surface. Plasma clot system permits clearcut morphological examination. Plasma clot system is in superiority to other culture systems. In this culture system several types of stromal-hemopoietic cells interactions were found, which probably correlate to in vivo interaction of these cells. PMID- 2224110 TI - [Effects of trophoblastic beta 1-glycoprotein (TBG) on the functional activity of different cell lines]. AB - The effect of TBG on the functional activity of different cell lines, spontaneous and Con A induced proliferation of PBL was studied. If concentration of TBG is higher than 50 mu kg/ml it suppresses the proliferation in many used cell lines, except choriocarcinoma and cancer of uterus. The reliable increasing of spontaneous proliferation of PBL, Jurkat and K-562 cells may be observed if concentration is more lower (0.5-15 mu kg/ml). However proliferation of other cell lines corresponds to control level, and Con A induced proliferation of PBL is inhibited. The effect was more marked at 48, as compared to 24 hours of cell incubation with TBG. PMID- 2224111 TI - [Polyanions inhibit the binding of autoantibodies with some cellular proteins]. AB - Effect of polyanions on reaction of the Ig from sera of patients with systemic lupus erythematosus and scleroderma with cellular proteins was studied by immunoblotting. It has been shown that dextran sulfate, heparin, denatured DNA and poly I inhibited the binding of autoantibodies with some polypeptides. The molecular weight of these antigens was determined. The molecular mechanism of immunological reactions studied and it's role in pathogenesis of autoimmune diseases is discussed. PMID- 2224112 TI - [Lack of species specificity in the action of immunosuppressive factors of tumor cells and absence of competition between them and recombinant interleukin-2 and phytohemagglutinin for lymphocyte membrane receptors]. AB - We studied some possible mechanisms of action of immunosuppressor factors (ISF) produced by tumor cells on lymphocyte proliferation. ISF of murine tumor cell lines inhibited the mitogen induced proliferation of murine splenocytes as well as human mononuclear blood cells. Normal human mononuclear blood cells or concanavalin A-activated murine spleen cells preincubated with phytohemagglutinin (PHA) or interleukin 2 (IL-2) respectively, were strongly suppressed by ISF in response to these activators. When preincubated with splenocytes or blood cells for 2 h at 4 degrees C following washing, ISF suppressed the lymphocyte proliferation as effectively as when being with cells during all period of cultivation. ISF inhibited mitogen-induced lymphocyte proliferation at low dilutions. There was no competition for lymphocyte membrane receptors between these functionally heterogenic kinds of ISF. Collectively, these results show that ISF acted when being attached to some lymphocyte membrane receptors. PMID- 2224113 TI - [Susceptibility of cells with different stage of malignancy to cytostatic action of resident peritoneal macrophages of Syrian hamsters]. AB - Syrian hamster non-activated resident peritoneal cells (PC) and peritoneal macrophages (Mph) was demonstrated. The in vivo selection of highly tumourigenic and highly metastatic variants of this strain correlated with their resistance to CSA PC and Mph in four cell variants out of five examined. The highly tumourigenic Syrian hamster embryo cells in vitro transformed by Rous sarcoma virus were highly resistant to CSA PC without selection in vivo. The resistance of highly malignant cells to CSA PC appeared to be unrelated to their ability to produce immunosuppressing prostaglandins of E type. PMID- 2224114 TI - [Intensive growth of human melanoma cells in a fibrin clot implanted in immunosuppressed mice]. AB - BRO human melanoma cells encapsulated within a fibrin clot grew rapidly in mice immunosuppressed (IS) by wholebody irradiation (5.5 or 6.5 Gy). After 8 days growth under the sub-renal capsule (SRC) of IS mice, the tumor volume increased 40-fold on the average, and histological and cytological examination showed that the growth consisted almost entirely of viable tumor cells. Marked tumor growth in IS mice also was observed after intraperitoneal implantation of fibrin clots containing BRO cells. SRC implantation of encapsulated BRO cells in pre irradiated mice offers a practical and reproducible method for evaluating the growth of human tumors in vivo. PMID- 2224115 TI - [Study of the effects of amyotrophic leukospongiosis causative agent on neuroglia cells in vitro]. AB - The influence of amyotrophic leukospongiosis (AL) causative agent on the ultrastructure of different types of cells of dissociated rat embryo brain and spinal cord cultures was studied. The AL agent belongs to the unconventional viruses (prions) and causes degenerative changes in the CNS. Large neurons and fibrous astrocytes were shown to be most sensitive. It was noted that the time of development and the degree of the dystrophic changes depend on the agent concentration. The destruction of cell membranes resulted in the pair neuron confluence. The formation of giant mitochondria with intramitochondrial inclusions was detected. It is supposed that the energetic apparatus of sensitive cells is primarily damaged by the infectious agent. PMID- 2224116 TI - [Role of stromal microenvironment in the regulation of bone marrow hemopoiesis after curantyl administration]. AB - Role of the stromal microenvironment in regulation of bone marrow hemopoiesis at the administration of the thrombocyte disaggregant curantyl was studied by the method of heterotopic transplantation of the mice bone marrow. It is shown that the action of curantyl on hemopoiesis is realised through the stem stromal cells of the bone marrow. It is noted that the inhibitory action of the preparation on proliferation of osteogenic precursor-cells is followed by activation of bone resorption processes in regenerating ectopic hemopoietic organ. Under the action of curantyl at low bone marrow cellularity in the focus of heterotopic hemopoiesis and femur an increase of mitotic activity in hemopoietic elements is noted. It is revealed that a phenomenon of ineffective megakaryocytopoiesis with intramedullary destruction of megakaryocytes leads to the local excretion of the thrombocyte released growth factor (TRGF) which has a compensatory character. PMID- 2224117 TI - Acute promyelocytic leukemia: another pseudoleukemia? PMID- 2224118 TI - Bleeding complications associated with cardiopulmonary bypass. AB - Bleeding after CPB has been difficult to characterize and its treatment equally difficult to standardize. The complexity of this problem is related to the hemostatic process, the technical variations in the operative procedures, and the many uncontrolled variables associated with CPB, including the effects of anesthetic or pharmacologic agents, the nature of the priming solution, hemodilution, hypothermia, the type of oxygenator, and the use of transfused blood products. Although there are multiple and generally predictable complex changes in the hemostatic mechanism during CPB, the temporary loss of platelet function is the most common and clinically relevant. This transient platelet dysfunction occurs in all patients undergoing CPB; however, it only causes excessive bleeding in a small percentage of patients. Unfortunately, it has not yet been possible to predict which patients will develop hemorrhagic complications, although prolonged pump times are a contributing risk factor. Over the past decade there has been extensive investigation into the management of bleeding associated with CPB, provoked primarily by the increased awareness of transfusion-transmitted viral diseases and the inappropriately excessive use of homologous blood products. Several approaches to autotransfusion of shed blood and autologus blood donation have been developed to minimize perioperative homologous blood transfusion. Pharmacologic agents such as desmopressin, aprotinin, and topical fibrin glues have also been introduced to improve hemostasis during CPB. The protease inhibitor aprotinin is particularly promising in the reduction of bleeding associated with CPB when given prophylactically. Aprotinin may provide new insights into the mechanism of CPB-induced platelet dysfunction. Desmopressin is indicated only for the treatment of bleeding after CPB. The management of bleeding associated with CPB will undoubtedly PMID- 2224120 TI - All-trans retinoic acid in acute promyelocytic leukemias. II. In vitro studies: structure-function relationship. AB - All-trans retinoic acid induces leukemic cells from patients with acute promyelocytic leukemia (M3) to differentiate in vitro to mature granulocytes which express the CD15 antigen and are capable of respiratory burst function. Of 35 M3 samples, only one failed to respond. In eight cases, we compared the efficacy of two naturally occurring isomers of retinoic acid, all-trans RA and 13 cis RA. Both isomers induce maximal differentiation at 10(-6) mol/L. The maximal response was maintained at 10(-7) mol/L for the all-trans but not for the 13-cis RA. We also observed that the metabolites 4-oxo-all-trans and 4-oxo-13-cis were effective at 10(-6) mol/L. This 1 order of magnitude difference in the in vitro differentiating potencies of all-trans RA and 13-cis RA in the blasts of promyelocytic leukemias predicts a difference in the clinical efficacy of the two drugs. PMID- 2224119 TI - All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. AB - Twenty-two patients with acute promyelocytic leukemia were treated with all-trans retinoic acid (RA, 45 mg/m2 per day) for 90 days. Of the 22, four patients were previously untreated, two were resistant after conventional chemotherapy, and 16 were in first (n = 11), second (n = 4), or third (n = 1) relapse. We observed 14 complete response, four transient responses, one failure, and three early deaths. Length of hospitalization and number of transfusions were notably reduced in complete responders. Correction of coagulation disorders and an increase of WBCs were the first signs of all-trans RA efficacy. Morphologic analysis performed at days 0, 15, 30, 45, 60, and 90 showed that complete remissions were obtained without bone marrow (BM) hypoplasia. Presence of Auer rods in the maturing cells confirmed the differentiation effect of the treatment. At remission, the t(15;17) initially present in 20 patients was not found. The in vitro studies showed a differentiation in the presence of all-trans RA in 16 of the 18 tested cases. The single nonresponder to all trans RA in vitro did not respond in vivo. Adverse effects of RA therapy--skin and mucosa dryness, hypertriglyceridemia, and increase of hepatic transaminases--were frequently noted. We also observed bone pain in 11 patients and hyperleukocytosis in four patients. Whether maintenance treatment consisted of low-dose chemotherapy or all-trans RA, early relapses were observed. Five patients are still in complete remission (CR) at 4 to 13 months. Our study confirms the major efficacy of all-trans RA in M3, even in relapsing patients. Remissions are obtained by a differentiation process. PMID- 2224121 TI - Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers. AB - A double-blind, placebo-controlled study of the pharmacokinetics and safety of multiple doses of recombinant human erythropoietin [rHuEPO 150 or 300 U/kg either by intravenous (IV) bolus or subcutaneously (SC)] in normal male subjects demonstrated that rHuEPO had a dose-related effect on the hematocrit independent of the route of administration and that multiple doses of rHuEPO had no direct pressor effects. When rHuEPO was injected IV, a monoexponential decrease in serum EPO level was evident for 18 to 24 hours postdose. Absorption of SC injected rHuEPO occurred more slowly, with relatively low serum EPO levels being maintained for 48 hours. All rHuEPO antibody titer determinations were negative. With the exception of significant increases in hemoglobin and hematocrit, no clinically significant changes occurred. No hypertensive, convulsive, or thrombotic events were observed. Of the adverse experiences observed in 10 subjects, none was considered clinically significant, and none of the subjects dropped out because of adverse experiences. PMID- 2224123 TI - Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. AB - The low frequency of plasma cells and the lack of specific cell surface markers has been a major obstacle for a detailed characterization of plasma cells in normal human bone marrow. Multiparameter flow cytometry enabled the identification of plasma cells in normal bone marrow aspirates. The plasma cells were located in a unique position in the correlation of forward light scattering, orthogonal light scattering, and immunofluorescent-labeled CD38. The identity of the sorted cell populations was confirmed by microscopic examination of Wright's stained slides and slides stained for cytoplasmic immunoglobulin using polyclonal antibodies reactive with light chains; ie, anti-kappa fluorescein isothiocyanate and anti lambda phycoerythrin (PE). The purity of the sorted plasma cells was greater than 97% (n = 4). The average frequency of plasma cells in normal bone marrow aspirates was low--0.25% of the nucleated cells (n = 7)--but surprisingly consistent between individuals (SD = .05; range 0.14% to 0.30%). A detailed analysis showed two distinct populations of plasma cells: (1) A population relatively smaller by forward light scattering expressed CD22, CD35, and sigE and was identified as early plasma cells (ie, lymphoplasmacytoid), and (2) a population larger by forward light scattering lacked these markers and was identified as mature plasma cells. The antigenic profile of the normal plasma cells was determined in two-color immunofluorescence studies. The expression of cell surface immunoglobulin G (IgG), IgA, IgE, IgD, IgM, and the cell surface antigens CD10, CD11b, CD13, CD11c, CD14, CD15, CD16, CD19, CD22, CD20, CD33, CD35, CD45, and HLA-DR was determined on the plasma cells. A significant heterogeneity in cell surface antigen expression was observed within the plasma cell population. Unexpectedly, myeloid-specific cell surface antigens such as CD33 and CD13 and the early B-cell antigen identified by CD10 were expressed on a proportion of plasma cells. These observations imply that the association of myeloid and early B-cell markers described in multiple myeloma may not be associated with the neoplasia but is a normal phenomenon. PMID- 2224122 TI - Autologous bone marrow transplantation in high-risk remission T-lineage acute lymphoblastic leukemia using immunotoxins plus 4-hydroperoxycyclophosphamide for marrow purging. AB - Fourteen patients with high-risk T-lineage acute lymphoblastic leukemia (ALL) in complete remission underwent autologous bone marrow transplantation (BMT) in an attempt to eradicate their residual disease burden. A combined immunochemotherapy protocol using a cocktail of two immunotoxins directed against CD5/Tp67 and CD7/Tp41 T-lineage differentiation antigens in combination with the in vitro active cyclophosphamide congener 4-hydroperoxy-cyclophosphamide (4-HC) was used to purge autografts. Despite high dose pretransplant radiochemotherapy and effective purging of autografts, 9 of 14 patients relapsed at a median of 2.5 months (range, 1.2 to 16.8 months) post BMT. Two patients remain alive and disease free at 26 and 28 months post BMT. We used a novel quantitative minimal residual disease (MRD) detection assay, which combines fluorescence activated multiparameter flow cytometry and cell sorting with leukemic progenitor cell (LPC) assays, to analyze remission bone marrow (BM) samples from T-lineage ALL patients for the presence of residual LPCs. Notably, high numbers of residual LPC detected in remission BM before BMT constituted a poor prognostic indicator, providing the first evidence for the biologic significance and clinical value of in vitro T-lineage ALL LPC assays. The median value for the residual leukemia burden before BMT, was approximately 8.6 x 10(3) LPC/10(8) mononuclear cells (MNC) (approximately 0.0086% LPC). Patients with a residual leukemia burden less than this median value appeared to have a better outlook for remaining free of relapse after autologous BMT than patients with a greater leukemia burden (53 +/- 25% v 14 +/- 13%, P = .006, Mantel-Cox). By comparison, the log kill efficacy of purging, the remaining numbers of LPC in purged autografts, or the estimated numbers of reinfused LPC, did not correlate with the probability of disease-free survival (DFS). These results indicate that the primary reason for the recurrence of leukemia was inefficient pretransplant radiochemotherapy rather than inefficient purging of autografts. PMID- 2224124 TI - The hematopoietic defect in aplastic anemia assessed by long-term marrow culture. AB - Thirty-two patients with aplastic anemia (AA) have been studied using the long term bone marrow culture (LTBMC) system. Of these patients, 26 had been treated with immunosuppressive therapy including antilymphocyte globulin (ALG) with or without androgens or high-dose methyl prednisolone. The remaining six patients either required no treatment or were studied before therapy was begun. Thirty-one of 32 patients (96%) had defective hematopoiesis in LTBMC with little or no evidence for the generation of primitive progenitor cells. The only exception was a patient with spontaneous recovery of aplasia in whom the defect was less marked. Crossover LTBMC experiments were performed in 23 cases by inoculating (1) patient marrow hematopoietic cells that had been depleted of adherent cells onto preformed, irradiated, normal stromas to assess the proliferative capacity of the hematopoietic cells, and (2) normal marrow hematopoietic cells that were depleted of adherent cells onto preformed, irradiated stromas from patients with AA to assess stromal function. Results of these experiments demonstrated a hematopoietic defect in all patients that was independent of the degree of hematologic recovery after ALG therapy. Only one patient had a probable stromal defect and this coexisted with a defect in the regenerative capacity of hematopoietic cells. We conclude that LTBMC is a sensitive method for detecting and defining the hematopoietic failure in AA. We suggest that the defective hematopoiesis present in all patients studied may be important in the pathogenesis of clonal evolution in AA. PMID- 2224125 TI - Developmental regulation of granulocytic cell binding to hemonectin. AB - Hemonectin (HN), a component of the bone marrow (BM) extracellular matrix which promotes adhesion of cells in the granulocytic lineage, was purified to near homogeneity and tested for its ability to mediate attachment of normal and leukemic cells of granulocytic lineage. Purified HN immobilized on plastic substrates promoted serum-free attachment of normal granulocyte/macrophage progenitor cells (CFC-GM), using an in situ attachment assay in which cell attachment is inhibited by specific polyclonal antisera. When unfractionated BM cells were allowed to attach to purified HN and stained in situ, HN preferentially bound cells at earlier stages of granulocytic differentiation. These observations were confirmed using cells of the HL-60 progranulocytic cell line which mirrored this differentiation-stage specific binding to HN. HN promoted attachment of 60% of uninduced HL-60 cells which were arrested at the progranulocyte stage, whereas only 15% of uninduced HL-60 cells attached to uncoated plastic and 4% to attached plastic coated with equal microgram quantities of bovine serum albumin (BSA). When HL-60 cells were induced to differentiate along the granulocytic pathway by incubation with dimethylsulfoxide (DMSO), attachment to hemonectin was reduced. Thus, both primary BM granulocytic cells and a granulocytic cell line show preferential attachment of those cells at earlier stages of differentiation. This developmentally regulated binding suggests a mechanism for release of maturing BM into the peripheral circulation. PMID- 2224126 TI - Enhanced endogenous leukotriene biosynthesis in patients treated with granulocyte macrophage colony-stimulating factor. AB - The hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM CSF) is being used in clinical trials for its potential in the treatment of hematopoietic insufficiency due to various causes. Involvement of leukotrienes in the effects of GM-CSF is suggested by analytical and pharmacologic evidence obtained in vitro. However, until now no data in support of a role of leukotrienes in GM-CSF action in vivo have been presented. In the present investigation this question was approached by measurement of endogenous cysteinyl leukotriene formation in patients treated with the cytokine for cytopenia induced by cytostatic drugs or for refractory anemia with excess of blasts (RAEB). Endogenous cysteinyl leukotriene formation was assessed by determination of urinary leukotriene metabolites using combined high-performance liquid chromatography and radioimmunoassay analysis. After GM-CSF administration a distinct increase in urinary cysteinyl leukotrienes was found in the cytopenic and the RAEB patients that ranged from 2.3- to 57-fold and 2.4- to 333-fold, respectively. In the cytopenic patients the increase in leukotriene production was correlated to an expansion of peripheral blood leukocytes; RAEB patients responded to GM-CSF with enhanced leukotriene biosynthesis even if the peripheral leukocytes decreased, possibly due to an abnormal number and/or irritability of leukotriene-producing cells. The increase in endogenous leukotriene production during therapy with GM-CSF may indicate that leukotrienes play a role in GM-CSF action in vivo. PMID- 2224127 TI - Isolation of large numbers of enriched human megakaryocytes from liquid cultures of normal peripheral blood progenitor cells. AB - Investigations linking human megakaryocyte development and cell biology have been hindered by an inability to obtain large, relatively pure megakaryocyte cell preparations from in vitro stem cell cultures. We report here that such preparations can be generated from liquid cultures of normal human peripheral blood mononuclear cells stimulated by a serum source of megakaryocyte colony stimulating activity (Meg-CSA, the 0% to 60% ammonium sulfate protein fraction of aplastic canine serum). Adherent-depleted peripheral blood mononuclear cells are suspended at 5 x 10(5) to 10(6) cells/mL in supplemented liquid culture medium, platelet-poor human plasma 20% (vol/vol) and 1 to 2 mg/mL serum Meg-CSA protein. After 12 to 14 days of incubation, megakaryocytes constitute 3.0 +/- 2.9% (mean +/- SD, n = 8) of the unseparated cultured cell population. Megakaryocytes can be enriched by counterflow centrifugal elutriation to a purity of 58 +/- 14% (+/- SD) with a recovery of 13 +/- 7% and a viability of 67 +/- 19%. This algorithm results in the average isolation of approximately 3 x 10(5) enriched megakaryocytes from a 100-mL starting volume of peripheral blood. Cultured megakaryocytes exhibit normal light and ultrastructural morphology by Wright Giemsa staining and electron microscopic analysis. After a 12-day culture interval, enriched megakaryocyte preparations exhibit morphologic stage distributions that are similar to normal human marrow. Stage distributions move rightward with culture duration indicating partial synchrony of megakaryocyte maturation. On cytospin preparations, megakaryocyte diameter averages 30.2 +/- 1.5 microns and increases with maturation stage. Flow cytometric analyses demonstrate the expression of platelet glycoproteins (GP) Ib and IIb/IIIa by the cultured megakaryocytes. The modal ploidy of the enriched cells at day 12 of culture is 16N and most remaining megakaryocytes are 8N or 32N. Liquid culture of serum Meg-CSA-stimulated human peripheral blood mononuclear cells represents a valuable investigative tool that should permit studies of human megakaryocyte biology that have not been possible in the past. PMID- 2224128 TI - Human macrophage colony-stimulating factor induces macrophage colonies after L phenylalanine methylester treatment of human marrow. AB - Macrophage-colony stimulating factor (M-CSF) has well-known effects on murine bone marrow, but its colony stimulating activity for human bone marrow is controversial. After treatment of human bone marrow with L-phenylalanine methylester (PME), macrophage-colonies (CFU-M) were induced by M-CSF in a dose dependent fashion. The optimal concentration of recombinant human-macrophage colony stimulating factor (rhM-CSF) was 1,000 U/mL. Purified human urine M-CSF had colony stimulating activity similar to rhM-CSF. Further studies were performed to determine the factors responsible for the enhanced CFU-M formation from PME treated marrow. Compared with nylon wool and carbonyl iron monocyte depletion methods, PME eliminated significantly more monocytes and myeloid cells. This observation suggested that these cells may release hematopoietic inhibitory factors for CFU-M. Low concentrations (1%) but not normal (10%) concentrations of blood monocytes were inhibitory (mean inhibition, 48%) to CFU-M. High concentrations of monocytes (50%) augmented CFU-M colonies. HL-60 conditioned media was used to simulate secretory products of early myeloid cells. HL-60 conditioned media (1%) inhibited CFU-M formation but not granulocyte macrophage or granulocyte colonies. We conclude that M-CSF has colony stimulating activity for human marrow that can be recognized after removal of inhibitory cells by PME treatment. PMID- 2224129 TI - New type of Bcr/Abl junction in Philadelphia chromosome-positive chronic myelogenous leukemia. AB - A new and rare type of Bcr/Abl junction between exon C3 of the 3' portion of the Bcr gene and Abl exon 2 has been identified in the leukemic cells of two Ph1 positive chronic myelogenous leukemia patients in chronic phase. This is the fourth type of Bcr/Abl junction so far identified in Ph1-positive hematologic malignancies and is a consequence of an unusual breakpoint position on chromosome 22 that falls approximately 20 kb downstream of the major breakpoint cluster region (bcr) of the Bcr gene. The new hybrid mRNA is 540 base pairs (bp) longer than that expressed by the K562 cell line and could codify for a Bcr/Abl protein carrying 180 additional aminoacids with respect to the larger P210 protein so far identified. The hematologic phenotype expressed by the two patients carrying this unusual type of Bcr/Abl rearrangement does not significantly differ from that commonly seen in chronic myelogenous leukemia. PMID- 2224130 TI - Shared idiotype expression by chronic lymphocytic leukemia and B-cell lymphoma. AB - Antiidiotype (Id) antibodies identify unique determinants within the surface immunoglobulin (Ig) that are present on B-cell tumors. Anti-Ids have been used for diagnosis and therapy of B-cell lymphoma and leukemia. A panel of 29 anti-Id monoclonal antibodies (MoAbs) that recognize shared idiotypes (SIds) on B-cell lymphomas was tested for reactivity with both B-cell leukemias and lymphomas. Ten of 40 (25%) cases of chronic lymphocytic leukemia (CLL) reacted with at least one of the 29 anti-SId MoAbs. Three cases reacted with more than one anti-SId MoAb, but there was no repetitive pattern of a single anti-SId MoAb reacting with a large proportion of CLL cases. In contrast, for B-cell lymphoma, in which 11 of 31 (36%) cases reacted, one anti-SId (B4-1) reacted with five of the positive cases; all were diffuse histology. Restricted anti-SId reactivity may lead to important insights into the etiology of certain B-cell lymphomas. In addition, these anti-SIds may obviate the need to develop "tailor-made" antibodies for individual patients. PMID- 2224131 TI - Transcellular biosynthesis of sulfidopeptide leukotrienes during receptor mediated stimulation of human neutrophil/platelet mixtures. AB - The ability of different cell types to cooperate in the metabolism of reactive intermediates of arachidonic acid such as leukotriene A4 (LTA4) is currently receiving considerable attention. Of critical importance is the demonstration that transfer of LTA4 could occur under conditions when relatively low amounts of LTA4 are produced such as would be expected for in vitro receptor-mediated stimulation. Stimulation of human neutrophils with a combination of chemotactic factor (formyl-methionyl-leucyl-phenylalanine, FMLP) and phagocytosable particles (opsonized zymosan) resulted in little production of LTC4 alone, but measurable quantities appeared when platelets were coincubated. When these agonists were added to platelets alone in the absence of neutrophils, no LTC4 was produced. In the presence of stimulated neutrophils, the final synthesis of LTC4 was shown to occur within the platelets (from neutrophil-derived LTA4) by experiments using platelets that had been prelabeled with 35S-cysteine to label intracellular platelet glutathione. Other 35S-labeled sulfidopeptide leukotriene metabolites were also produced in this coincubation of neutrophils and platelets. The observed synergy between FMLP and opsonized zymosan in the production of LTC4 when neutrophils and platelets were coincubated may involve priming the neutrophil for LTA4 production. Activation of platelets or endothelial cells with thrombin did not alter the capacity of either cell to convert exogenously added LTA4 into LTC4. This would support the suggestion that even when platelets are activated they retain their capacity to metabolize LTA4 into LTC4. Finally, previous exposure of the platelets to LTA4 did not affect subsequent metabolism of arachidonic acid by the cyclooxygenase pathway to thromboxane A2 (TXA2) except at very high concentration of LTA4. These results suggest that cell-cell interactions may be critical determinants of the profile of eicosanoids produced in physiologic and pathophysiologic circumstances. In particular, we believe that both endothelial cells and platelets can, together with neutrophils, contribute relatively large amounts of sulfidopeptide leukotrienes to inflammatory and thrombotic events. These cell-cell interactions are aspirin-insensitive; therefore, aspirin-treated platelets are capable of synthesizing the vasoconstrictor LTC4 from neutrophil LTA4 at a time when they can no longer produce thromboxane. PMID- 2224132 TI - In vitro rosetting, cytoadherence, and microagglutination properties of Plasmodium falciparum-infected erythrocytes from Gambian and Tanzanian patients. AB - To understand the molecular mechanisms that lead to sequestration of red blood cells infected with mature stages of Plasmodium falciparum and to examine the relevance of earlier studies on adherence properties of laboratory-derived P falciparum parasites to the natural parasite population, we analyzed Gambian and Tanzanian isolates for in vitro cytoadherence and antibody-mediated microagglutination. Eighteen cryopreserved isolates of ring-stage parasites were cultured for 20 to 30 hours in vitro, in the patients original erythrocytes, to the trophozoite and schizont stage. All parasites were positive in the microagglutination assay with at least one of four African hyperimmune sera. In a rosetting assay, only 2 of the 18 isolates were strongly positive (35% and 41% of parasitized erythrocytes with more than two uninfected cells bound). Thirteen isolates showed either intermediate (5% to 18%) or low (less than 5%) rosetting while three isolates did not form rosettes. Infected cell-binding of the different isolates to immobilized CD36 or thrombospondin, or C32 melanoma cells correlated with the percentage of mature parasites in the blood samples (r = .932 for CD36, r = .946 for thrombospondin, and r = .881 for C32 melanoma cells). There was a high correlation between binding to CD36 and thrombospondin (r = .982). The extent of infected cell rosetting with uninfected cells in these blood samples was not correlated with these other receptor properties. We also observed coexpression of rosetting and cytoadherence receptors on the same parasitized erythrocytes. PMID- 2224133 TI - Autologous bone marrow transplantation in multiple myeloma: identification of prognostic factors. AB - Multiple myeloma remains a universally fatal malignancy with a median survival time not exceeding 3 years. A clinical trial was undertaken to determine feasibility and efficacy of marrow-ablative chemoradiotherapy supported by unpurged autologous bone marrow (ABMT) and to define prognostic variables. Total body irradiation and either melphalan or thiotepa were administered to 55 patients (median age 53 years; range 20 to 66 years). The group of 21 patients with resistance to standard melphalan-prednisone and to continuous infusions of vincristine and Adriamycin with high dose dexamethasone (VAD) included 7 with primary unresponsive disease and 14 with resistant relapse; among the 34 patients achieving remission with the VAD regimen, 14 were in first and 20 in a subsequent remission. Marked cytoreduction by greater than or equal to 75% was observed among all 21 patients with refractory myeloma, whereas further cytoreduction of this magnitude was noted in only 56% of the 34 patients already in remission after VAD. Five of the 6 early deaths among all 55 patients occurred in the 14 patients with resistant relapse, none of whom achieved complete remission and who, as a group, had median durations of relapse-free and overall survival of only 8 and 7 months, respectively. Among the 41 remaining patients, there was only one early death, and 27% achieved complete remission including a 36% incidence among the 14 patients treated in first remission; their projected 4 year survival rate was 82% regardless of their disease status (first or later remission or primary resistance). When information about sensitivity to prior therapy is unavailable, the presence before ABMT of both high beta-2 microglobulin levels (greater than 3 mg/L) and non-IgG isotype helped identify 9 among the 55 patients with a very poor prognosis: all 8 responders relapsed within 9 months, and 8 patients died within 15 months. By contrast, a 4-year projected survival rate of over 70% for the other patients (about 80% of this series) justifies further investigation of this novel treatment approach in comparison with standard dose regimens. Our results indicate that marrow-ablative therapy cannot be recommended for myeloma patients with resistant relapse or those with a combination of risk factors (advanced tumor burden, absence of IgG isotype). The apparent lack of an adverse effect of even marked plasmacytosis in autografts (up to 30%) emphasizes the need for better cytoreduction rather than bone marrow purging. PMID- 2224134 TI - Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. AB - A randomized trial of 12.0 Gy versus 15.75 Gy of total body irradiation (TBI) was performed in patients with acute myeloid leukemia undergoing allogeneic marrow transplantation while in first complete remission. All patients received 120 mg/kg cyclophosphamide followed by TBI and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft versus-host disease (GVHD). Thirty-four patients received 2.0-Gy fractions of irradiation daily for 6 days and 37 received 2.25-Gy fractions daily for 7 days. The 3-year actuarial probabilities for relapse-free survival were 0.58 for the patients who received 12.0 Gy and 0.59 for those who received 15.75 Gy. The 3 year probabilities of relapse were 0.35 for the 12.0 Gy group and 0.12 for the 15.75 Gy group (P = .06). The 3-year probabilities of transplant-related mortality were 0.12 and 0.32, respectively (P = .04). The probability of moderate to severe acute GVHD was 0.21 for the 12.0 Gy group and 0.48 for the 15.75 Gy group (P = .02). Patients exposed to the higher irradiation dose received less immunoprophylaxis against, and had a higher incidence of, acute GVHD. The increased dose of TBI significantly reduced the probability of relapse but did not improve survival because of increased mortality from causes other than relapse. PMID- 2224135 TI - Induction of donor-type chimerism in murine recipients of bone marrow allografts by different radiation regimens currently used in treatment of leukemia patients. AB - Three radiation protocols currently used in treatment of leukemia patients before bone marrow transplantation (BMT) were investigated in a murine model (C57BL/6--- C3H/HeJ) for BM allograft rejection. These include (a) a single dose of total body irradiation (8.5 Gy TBI delivered at a dose rate of 0.2 Gy/min), (b) fractionated TBI (12 Gy administered in six fractions, 2 Gy twice a day in 3 days, delivered at a dose rate of 0.1 Gy/min, and (c) hyperfractionated TBI (14.4 Gy administered in 12 fractions, 1.2 Gy three times a day in 3 days, delivered at a dose rate of 0.1 Gy/min). Donor-type chimerism 6 to 8 weeks after BMT and hematologic reconstitution on day 12 after BMT found in these groups were compared with results obtained in mice conditioned with 8 Gy TBI delivered at a dose rate of 0.67 Gy/min, routinely used in this murine model. The results in both parameters showed a marked advantage for the single dose 8.5 Gy TBI over all the other treatments. This advantage was found to be equivalent to three- to fourfold increment in the BM inoculum when compared with hyperfractionated radiation, which afforded the least favorable conditions for development of donor type chimerism. The fractionated radiation protocol was equivalent in its efficacy to results obtained in mice irradiated by single-dose 8 Gy TBI, both of which afforded a smaller but not significant advantage over the hyperfractionated protocol. This model was also used to test the effect of radiation dose rate on the development of donor-type chimerism. A significant enhancement was found after an increase in dose rate from 0.1 to 0.7 Gy/min. Further enhancement could be achieved when the dose rate was increased to 1.3 Gy/min, but survival at this high dose rate was reduced. These results demonstrated indirectly that dose rate affects the expression of host-type pluripotent stem cells, the progeny of which appear 3 to 6 weeks after treatment with 8 Gy TBI delivered at a dose rate of 0.1 Gy/min, but which are eradicated if radiation is delivered at a dose rate of 1.3 Gy/min. PMID- 2224136 TI - Contamination of peripheral blood stem cell harvests by circulating neuroblastoma cells. AB - Peripheral blood stem cells (PBSC) are being used as one alternative to autologous marrow rescue for patients with neuroblastoma and other solid malignancies. Some physicians prefer use of PBSC because less risk of tumor contamination is believed to exist. This hypothesis was evaluated by immunocytologic analysis of blood samples and concurrently drawn bone marrow (BM) samples and of PBSC harvests obtained from 31 patients with disseminated neuroblastoma. We found circulating neoplastic cells in 75% of specimens analyzed at diagnosis, in 36% during therapy, and in 14% of PBSC harvests. Tumor cells in blood obtained during therapy did not appear until 3 months after the time of diagnosis. Clearance of circulating neuroblastoma cells was documented after two courses of induction chemotherapy. Six of 13 patients with minimal or no BM disease had positive blood specimens. We conclude that substantial risk of tumor contamination of PB harvests exists and recommend that induction chemotherapy be administered before hematopoietic progenitor cells are collected from blood. PMID- 2224138 TI - Involvement of the p53 tumor suppressor gene in Ph1-positive and Ph1-negative myeloid leukemia. PMID- 2224137 TI - Adenine and guanine nucleotide metabolism during platelet storage at 22 degrees C. AB - Adenine and guanine nucleotide metabolism of platelet concentrates (PCs) was studied during storage for transfusion at 22 +/- 2 degrees C over a 7-day period using high-pressure liquid chromatography. There was a steady decrease in platelet adenosine triphosphate (ATP) and adenosine diphosphate (ADP), which was balanced quantitatively by an increase in plasma hypoxanthine. As expected, ammonia accumulated along with hypoxanthine but at a far greater rate. A fall in platelet guanosine triphosphate (GTP) and guanosine diphosphate (GDP) paralleled the fall in ATP + ADP. When adenine was present in the primary anticoagulant, it was carried over into the PC and metabolized. ATP, GTP, total adenine nucleotides, and total guanine nucleotides declined more slowly in the presence of adenine than in its absence. With adenine, the increase in hypoxanthine concentration was more rapid and quantitatively balanced the decrease in adenine and platelet ATP + ADP. Plasma xanthine rose during storage but at a rate that exceeded the decline in GTP + GDP. When platelet ATP + ADP was labeled with 14C adenine at the initiation of storage, half of the radioactivity was transferred to hypoxanthine (45%) and GTP + GDP + xanthine (5%) by the time storage was completed. The isotopic data were consistent with the presence of a radioactive (metabolic) and a nonradioactive (storage) pool of ATP + ADP at the initiation of storage with each pool contributing approximately equally to the decline in ATP + ADP during storage. The results suggested a continuing synthesis of GTP + GDP from ATP + ADP, explaining the slower rate of fall of GTP + GDP relative to the rate of rise of plasma xanthine. Throughout storage, platelets were able to incorporate 14C-hypoxanthine into both adenine and guanine nucleotides but at a rate that was only one fourth the rate of hypoxanthine accumulation. All of these data should be helpful in improving the function and viability of PC as currently stored for 5 days, in devising methods for storage beyond 5 days, and in the development of synthetic media for PC storage. PMID- 2224139 TI - Three-base deletion in exon 3 of the beta-globin gene produced a novel variant (beta gunma) with a thalassemia-like phenotype. PMID- 2224140 TI - The Brazilian type of nondeletional A gamma-fetal hemoglobin has a C----G substitution at nucleotide -195 of the A gamma-globin gene. PMID- 2224141 TI - Treatment of Cooley's anemia: deferoxamine provocation test. PMID- 2224142 TI - HLA 1990. AB - The HLA system encompasses approximately one thousandth of the human genome and contains a series of closely linked loci coding for molecules which provide the context for the recognition of antigens by T lymphocytes. Within the HLA system, several phenotypically expressed and genomic polymorphisms can be distinguished. These polymorphisms are described and the main objectives for the future research are discussed. PMID- 2224144 TI - Patterns of contact phase proteins indicating neuropathy in diabetic patients. AB - In 42 outpatients of the diabetology division, coagulation and fibrinolysis variables were determined in order to detect typical patterns of results with which it was possible to discriminate between three groups with different diabetic complications (17: no complication, 7: angiopathy alone, 18: neuropathy with or without other complications). There was a statistically significant discriminatory function involving C1-inhibitor concentration, high molecular weight kininogen coagulant activity and fibrinogen as the most decisive variables. The neuropathy group was appropriately separated from the others with an 81% correct reclassification. Heparin cofactor II, histidine-rich glycoprotein, alpha 2-macroglobulin, pre-kallikrein and factor XII had no discriminative power. PMID- 2224143 TI - Capillary leak syndrome during low dose granulocyte-macrophage colony-stimulating factor (rh GM-CSF) treatment of a patient in a continuous febrile state. AB - A 20 years old man with peripheral primitive neuroectodermal tumor involving the bone marrow received 12 Gy fractionated total body irradiation, 140 mg/m2 melphalan, 1800 mg/m2 etoposide, and 1500 mg/m2 carboplatin for consolidation of first remission. Thereafter, 250 micrograms/m2/day recombinant human granulocyte macrophage colony-stimulating factor (rh GM-CSF) (Behring Werke) were administered as continuous infusion 4 days after infusion of autologous bone marrow and peripheral stem cells to accelerate granulocyte reconstitution for control of a continued febrile state. The clinical picture of capillary leak syndrome developed with weight gain, pleural effusions and peripheral edema. The patient's condition stabilized after discontinuation of rh GM-CSF. Eight days later he died of invasive aspergillosis. The clinical course of our patient suggests a potentially fatal toxic effect of rh GM-CSF, even in low dose, in the setting of septicemia or fungemia. PMID- 2224146 TI - Transient pancytopenia. A report from the International Agranulocytosis and Aplastic Study. AB - From a population-based study on the incidence of potentially drug-associated blood dyscrasias 28 cases were identified with pancytopenia. Who recovered within 90 days after diagnosis. Early recovery occurred more frequently in patients showing normal or increased cellularity of the bone marrow than in patients with bone marrow hypoplasia. Median recovery times of leukocytes were 14 and 10 days and of platelets 21 and 9 days in patients with and without bone marrow hypoplasia, respectively. Age and sex distribution were similar in both groups. Of 28 patients, 11 reported a period of fever before onset of pancytopenia. Sixteen patients in whom information on drug use was available had taken a median of 4 drugs before the onset of symptoms that were related to pancytopenia. From these results we present the hypothesis that transient pancytopenia with or without marrow hypoplasia can be the expression of the same type of bone marrow injury and that drugs or viral infections should be considered as etiological factors. PMID- 2224145 TI - Sugar receptors of the stromal cell layer in human long-term bone marrow cultures: their presence, modulatory responses to changes in the microenvironment and potential role in cellular adhesion. AB - Intimate cellular contacts and coordinated supply of regulatory factors are required to maintain the still inexplicable dynamic equilibrium of hemopoiesis. To infer the potential participation of protein-carbohydrate interaction in this complex process, human long-term bone marrow cultures were initiated from eleven donors, and the adherent cell layer was characterized enzyme- and immunohistochemically. Utilizing an array of carrier-immobilized carbohydrate ligands and sulfated polysaccharides as probes, specific binding of various constituents of the carbohydrate chains of cellular glycoconjugates to the stromal cells was unmistakably disclosed. Biochemical analysis, employing glycocytologically effective ligands in affinity chromatography, corroborated this result. The extent of binding was markedly lower in the two samples, derived from leukemia patients. Pronounced adaptive responses for this characteristic followed changes in the culture microenvironment that are known to influence qualitative and quantitative aspects of hemopoiesis in vitro, namely omission of hydrocortisone and horse serum or addition of cytokines. Similarly, such adaptive modulation occurred on the level of accessible cell surface receptors, monitored by neoglycoenzymes. These binding sites can be involved in mediation of cellular interactions, as revealed in a model system by the interference of N-acetyl-D galactosamine in cell adhesion. Overall, the results support the idea that glycobiological recognition may contribute to the functional integrity of the stromal cell layer as well as provide the basis for further analysis. PMID- 2224148 TI - Hairy cell leukemia with ring-shaped nuclei. PMID- 2224147 TI - Congenital diserythropoietic anemia type I. Report on monozygotic twins with associated hemochromatosis and short stature. AB - We report the first occurrence of congenital dyserythropoietic anemia type I in monozygotic twins and the seventh familial occurrence to our knowledge. Mild hemochromatosis is present in the two children but has not yet required iron chelation. Moderate growth retardation, which seems to be related to pituitary failure, is also present. PMID- 2224149 TI - Blood transfusion: the impact of new technologies. PMID- 2224150 TI - Automation in blood grouping: impact of microplate technology. PMID- 2224151 TI - Flow cytometry: its applications to immunohaematology. AB - Flow cytometry, using fluorescent probes, has only recently been applied to practical aspects of immunohaematology. It has been used for the detection and quantitation of cell-bound immunoglobulins and complement, minor cell populations, cellular antigens, and platelet and granulocyte antibodies. Practical applications of detecting minor cell populations have been successful in determining the extent of fetal maternal haemorrhage; determining the survival of transfused RBCs (small and large volumes); demonstrating RBC chimaerism (e.g. following bone marrow transplantation) and RBC mosaicism (e.g. demonstration of the McLeod phenotype carrier status). A large variety of cellular antigens have been demonstrated on RBCs, platelets and white cells using flow cytometry. Quantitation of RBC antigens by flow cytometry has been found to be much more objective and accurate than the routinely used serological approaches for establishing zygosity in paternity studies. Flow cytometry has been found to be a sensitive, objective and reproducible method for detecting platelet auto-and alloantibodies, and has also been used to detect granulocyte antibodies. More recently, it has been used to detect antibodies to monocytes and lymphocytes. As flow cytometers become more commonly available, many of these applications may become routine in clinical pathology laboratories. PMID- 2224152 TI - ADCC and other cellular bioassays for predicting the clinical significance of red cell alloantibodies. PMID- 2224153 TI - Microbiological screening of blood donations. PMID- 2224154 TI - Intraoperative blood salvage. AB - Interest in and use of IBS have increased recently. This form of haemotherapy involves the retrieval of blood shed perioperatively. IBS, together with other forms of ABT, has gained a prominent role in transfusion medicine, largely due to an increased awareness of the risks associated with transfusion of homologous blood. In addition to conserving erythrocytes, IBS prevents disease transmission, other adverse transfusion reactions, and alloimmunization to antigens in blood cells and plasma which may result from homologous blood use. An array of IBS devices is presently available, ranging from disposable canisters to complete processing systems. The devices are capable of recovering, filtering, washing and reinfusing shed erythrocytes. They can be divided into slow-flow and rapid-flow systems based on the rapidity of blood processing. Most systems use a dual channel aspiration cannula through which shed blood is aspirated and mixed with anticoagulant solution. The salvage procedure requires operator control at every step, even for the highly automated instruments. Various health care personnel have been trained to operate IBS equipment; a transfusion service nurse with blood bank expertise has proved to be a highly reliable operator in our practice. Extensive clinical observation has shown that salvaged erythrocytes function and survive normally. IBS has been applied in many surgical fields; it has two relative contraindications: its use in areas affected by infection or malignancy. Operative procedures characterized by large blood losses provide a cost-efficient application of IBS, including cardiac surgery, orthopaedic procedures, trauma, vascular surgery, and liver transplantation. New, highly efficient technology is emerging that is capable of recovering other blood components. Consequently, what presently amounts to erythrocyte recovery will be expanded shortly to include platelets and plasma, with its many constituents. PMID- 2224156 TI - Novel intravenous immunoglobulins and their applications. PMID- 2224155 TI - Application of computers in blood transfusion. PMID- 2224157 TI - Genetically engineered and affinity purified plasma proteins. PMID- 2224158 TI - [Agent orange. Passion and reason]. PMID- 2224159 TI - [Proto-oncogenes activation in human solid tumors]. AB - Genetic alterations in solid human tumors occur in several groups of genes, one of which contains the proto-oncogenes. These genes are involved in the control of cell proliferation and become activated in oncogenes by various mechanisms. These activations are reviewed herein. PMID- 2224161 TI - [Incidence of nosocomial infections in an cancer center: clinical and bacteriologic data]. AB - Over a 5 month period, a study of the incidence of nosocomial infections (NI) was carried out in the Leon Berard Oncology Center (Lyons). It comprised 1,551 patients classified in groups according to the site of origin of the underlying malignancy. The respective frequency of the different types of nosocomial infections and the responsible agents was evaluated in each group and the incidence was calculated per day of hospitalization. The overall incidence of NI was 11.29 per 1,000 patient-days, with a maximal value of 20.04 for patients suffering from lymphomas. The most frequently encountered infections were bacteremias (22.7%), followed by urinary tract infections (20.8%) and wound infections (20.5%). The most frequent causative agents of NI were Escherichia coli (25.8%), Pseudomonas aeruginosa (13.9%), Staphylococcus aureus (9.8%) and Staphylococcus epidermidis (9.8%). The latter micro-organism together with Escherichia coli were the most frequent causative agents of bacteremias. Even though cancer patients are particularly prone to developing infections, the incidence of NI could be reduced thanks to a program of control and surveillance of infectious episodes during hospitalization. PMID- 2224160 TI - [Response in patients with melanoma to immunization using melanoma oncolysates of vaccine virus]. AB - Thirty-two patients with high risk melanoma (either primary melanoma of the limbs or trunk, or recurrent melanoma) and clinically disease-free following appropriate surgical treatment were immunized with a vaccinia virus oncolysate made from a pool of 4 human melanoma cell lines. Injections were given id weekly for 3 months, and then bi-monthly for a further 21 months or until relapse. Treated patients have been under study for 11-72 months, and 15 of them for more than 36 months. Twelve patients received a full 24-month treatment: 3 relapsed and 10 are alive (9 of them disease-free) with a survival of 34-72 months. One patient is still under treatment. Nineteen patients relapsed during treatment: among the 13 patients that relapsed early during the course of treatment, 9 patients died after a survival of 5-30 months and 4 are alive with a survival of 30-59 months; among the 6 patients that later relapsed, 2 patients died after a survival of 21 and 29 months and 4 are alive with a survival of 16-69 months. An analysis of the patients' disease-free survival and overall survival was made using the actuarial method, and limited to 5 years: the disease-free survival curve shows a 35% plateau reached after 40 months, and the survival curve shows a 60% plateau reached after 30 months. The patients' responses to the immunization antigens expressed by the oncolysate were studied. Lymphocytes from immunized patients do respond in vitro to the stimulation by oncolysate in the presence of low amounts of IL-2, and this response is greater than that of normal individuals. IgG antibody production to gangliosides with N-glycolyl neuraminic acid is of prognostic significance, the increase in IgG anti-ganglioside antibody in patients after 3 and 6 months of treatment being linked to the absence of relapse in these patients. Finally, preliminary results show, in several patients under treatment, the appearance of antibodies directed against a 31 kD protein of the oncolysate not detectable in the vaccinia virus or in melanoma cell lysates. Such results are in accordance with previously reported ones from similar studies conducted by other investigators and tend to indicate the efficacy of vaccinia virus oncolysate immunization in the treatment of high risk melanoma. PMID- 2224163 TI - [Antihormonal treatments in breast cancer in the woman. Role of estrogen antagonists]. AB - Hormone treatment of breast cancer has been common practice for many years. More recently, findings on the hormonal mechanism of action on the target cells have provided a better approach of hormone-dependency and prognosis. Moreover, new hormonal synthetic molecules are now available. They are effective on specific activities of the endocrine system in well defined conditions. Administration of these drugs requires caution and previous evaluation of the patients' hormonal status conjugated to biological data of the tumor itself in view of obtaining efficient control of tumor growth. PMID- 2224162 TI - [Resection of the thoracic wall in oncology]. AB - Based on our experience with 12 patients who underwent wide anterior chest wall resection in our institute, we attempt to define the indication of the different techniques for reconstruction by musculo-cutaneous flaps according to the extent of resection and location in the chest wall. The pectoralis major flaps are simple and important in the reconstruction of sternal defects; especially when dense retrosternal fibrosis has already developed after radiotherapy. The latissimus dorsi flaps are reliable and thick and suitable for coverage of major tissue loss. A new technique is also described for reconstruction of major anterolateral chest wall defects as well as sternal defects by a latissimus dorsi osteo-muscular flap. The external oblique musculo-cutaneous flaps are used to cover defects in the lateral chest wall below the 5th rib. Pedicled omental flaps are complementary flaps and can be used when muscle flaps are insufficient to replace significant tissue loss. Respiratory problems arising from paradoxical chest wall movement are temporary and may be encountered in the immediate post operative period. Because of the development of fibrosis and of a better adaptation of the patient, this condition is well tolerated during the month following operation. PMID- 2224164 TI - [Conservative treatment of breast cancer (the Lyon experience during 1963-1983)]. AB - Over a 20-year period (1969-1983), 570 infiltrating primary breast carcinomas were conservatively treated in Lyons. Two different protocols were used: a first group of 162 patients with T1 T2 less than 3 cm NO lesions was treated, between 1963 and 1973, by lumpectomy and external beam irradiation with 60cobalt. The 5 and 10 year overall survival rates are 86% and 66% respectively. Local and regional failure rates are 10% and 2.5%. Cosmetic result was good or excellent in 70% of patients with only 5% poor results; a second group of 408 patients with T1 T2 less than 3 cm lesions was treated between 1973 and 1983 by tumorectomy and axillary dissection, followed by cobalt irradiation and 192iridium boost. The 5 year overall survival rate was 90% and, at 5 years, the probability of failure is 5% in the breast and 2% in the axilla. Cosmetic results are comparable in the 2 groups. Comparison of these 2 groups indicates an improvement in local control with Iridium boost. No obvious change in axillary recurrence rate and overall survival rate was observed. Boost modalities are discussed, with regard to cosmetic results. A prospective randomized study was initiated in 1986, in order to assess the value of the boost in the conservative treatment of breast cancer. PMID- 2224165 TI - [Adoptive immunotherapy with interleukin 2 in oncology]. AB - Forty-seven patients with renal carcinoma were included in first line or rescue protocols of immunotherapy including IL2 alone or in association with LAK cells, INF alpha or TNF. The toxicity was mild and the mortality was 2% (1 patient). The response rate was 26%. Nineteen children with neuroblastoma received IL2 either alone or in combination with LAK cells. The morbidity and mortality were higher in patients with end stage disease who had previously received high dose and prolonged chemotherapy. In contrast, the toxicity was mild and transient in patients treated in the months following autologous bone marrow transplantation. The only complete response observed was in 1 child treated with IL2, 4 months after high dose chemotherapy and ABMT. Immunological analysis showed that the immunomodulatory effect of IL2 is very different depending on whether IL2 is used alone or in combination with other cytokines; moreover, the biological effect of IL2 is dependent on the immunological status of the patients prior to IL2 therapy. PMID- 2224166 TI - [Developments in the treatment of osteosarcoma since 1979. Report of the statistics at the Centre Leon-Berard]. AB - Seventy-two patients with a localized osteosarcoma were treated between September 1979 and December 1987 by neoadjuvant chemotherapy, local surgery and post operative chemotherapy. Chemotherapy regimens varied throughout the years but always comprised high dose methotrexate with leucovorin rescue and adriamycin pre operatively for children under the age of 15, and ifosfamid and cis platinum in adults. Post-operative chemotherapy for bad responders (greater than 10% of residual malignant cells), was at first an association of adriamycin and cis platinum, and later of holoxan and cis platinum. Surgery changed from amputation to local conservative surgery (graft or prosthesis) which is now the most frequent surgery--61% of the patients are alive and disease-free at 5 years. Good responders to pre-operative chemotherapy have a much better prognosis (81% at 5 years) than bad responders (45%). There is no significant difference according to age or pre-operative chemotherapy regimen. PMID- 2224167 TI - [Prognostic factors in the response of a first line chemotherapy in advanced breast cancer]. AB - Anthracyclines containing regimen are widely used in advanced breast cancer. The response to first line chemotherapy varies according to many individual factors and the theoretical response to a given protocol cannot predict the response of a patient. A randomized clinical trial (ERASME) was initiated in order to evaluate the more appropriate first line chemotherapy scheme in advanced breast cancer. Prognostic factors were included in a multiple logistic regression to explain the response after the first 3 chemotherapy courses (monthly FEC). Three factors were found to be statistically significant: adjuvant hormonotherapy, loco-regional metastases, adjuvant adriamycin containing regimen (pejorative prognostic factor). By combining these factors, this statistical model enables us to predict a response rate to a first line chemotherapy from 27 to 87%. Such a model can be taken into account in a decision-making procedure of first line chemotherapy in advanced breast cancer. PMID- 2224168 TI - Social connections and risk for cancer: prospective evidence from the Alameda County Study. AB - The association between social connections and cancer incidence, mortality, and prognosis during 17 years of follow-up was examined in a population-based sample of 6,848 adults who lived in Alameda County, California, in 1965. Estimates of relative hazards were derived from Cox regression modeling, adjusting for age, smoking, physical health at baseline, alcohol consumption, and adjusted household income. Women who were socially isolated were at significantly elevated risk of dying of cancer of all sites and of smoking-related cancers. Social connections were not prospectively associated with cancer incidence or mortality among men, but men with few social connections showed significantly poorer cancer survival rates. These patterns of risk are consistent with the biology of different cancer outcomes. They also suggest a different role for social isolation in cancer among men and women. PMID- 2224169 TI - Behavioral differences in the interactions between Type A and B mothers and their children. AB - Fifty-seven women participating in a study of family reorganization following parental separation were grouped as Type A or B on the basis of the Jenkins Activity Survey. They were observed interacting with their children during two tasks, one of which elicited more directive and involved interaction than the other. Type A mothers were particularly directive, especially when interacting with sons and during the task-oriented condition. Although children's behavior was coded and analyzed as a function of mothers' Type A or B status, few differences in children's behavior were found. PMID- 2224170 TI - Manifest hostility may affect habituation of cardiovascular reactivity in blacks. AB - In a study of cardiovascular reactivity to dietary manipulation of sodium and calcium, we pretested 30 young black normotensive males who were equally divided by positive and negative parental histories of hypertension with a 12-item anger questionnaire we devised and the Cook-Medley Hostility, Manifest Hostility, Overcontrolled Hostility, and Inhibited Hostility scales of the Minnesota Multiphasic Personality Inventory. Contrary to expectations, we found no correlation of resting blood pressure or cardiovascular reactivity to repeated mental demands with the two measures of inhibited hostility. We did, however, find resistance to habituation of cardiovascular reactivity in subjects with high Manifest Hostility and positive family histories of essential hypertension. Our findings suggest that vulnerability to hypertension may be revealed by the perseveration of blood pressure reactivity to repeated mental challenge. We propose that the perseveration of blood pressure reactivity is a disinhibitory phenomenon caused by a difficulty in the management of multiple inhibitory demands that disrupts the natural course of habituation and could be an important etiologic factor in essential hypertension. PMID- 2224171 TI - Life stress and social supports in depressed inpatients. AB - The presence of adequate social supports has been associated with a reduced incidence of psychological symptoms. It is unclear, however, whether the protective influence of social supports is because of a direct positive effect on psychological functioning or a stress-buffering effect. Furthermore, most research on life stress and social supports has focused on community-based rather than clinical samples. The present study attempts to clarify the relationship between life stress and social supports related to psychological symptoms in 84 adult, nonpsychotic, depressed inpatients. Subjects were categorized according to their responses on the Life Experiences Survey and the Social Supports Inventory. Subjects were then assessed using both structured interviews and self-report measures of depression and suicide potential, as well as other psychological symptoms. Although both life stress and social supports were significantly related to a variety of psychological symptoms, the interaction between these variables was not significantly related to psychological symptomatology. Life events and social supports were found to exert their effects independently. This argues against the stress-buffering theory in favor of the direct-effects theory of social supports, at least when applied to inpatient samples. PMID- 2224172 TI - Lipids and lipoproteins in a triethnic sample of 5- or 6-year-old Type A or Type B children. AB - The Type A behavior pattern (TABP) has been proposed as a risk factor for coronary heart disease (CHD). Several studies have indicated an association between Type A behavior and serum cholesterol levels. If the effects of TABP are mediated by conventional CHD risk factors, evidence for a causal relationship between TABP and CHD would be strengthened if associations were detected among the young. This paper addresses the following: (1) Do levels of serum lipids and lipoproteins among young children vary by ethnicity, gender, or TABP? (2) Can obtained differences be accounted for by possible confounding factors, such as SES or body composition? ANCOVA revealed no significant ethnic, gender, or TABP effects for total serum cholesterol or HDLc. Analyses of LDLc and triglycerides disclosed significant main effects for gender and for ethnicity. A Competition subscale by ethnicity interaction was the only effect to approach statistical significance for TABP. The strongest findings were a replication of differences in lipid and lipoprotein risk factors by ethnicity. PMID- 2224173 TI - Charity, translation, and the language of medical learning in medieval England. PMID- 2224174 TI - The German model of training physicians in the United States, 1870-1914: how closely was it followed? PMID- 2224175 TI - Rural medical practice in the 1880s: a view from central Wisconsin. PMID- 2224176 TI - American military medicine in the mid-nineteenth century: the experience of Alexander H. Hoff, M.D. PMID- 2224177 TI - The wealth of nineteenth-century American physicians. PMID- 2224178 TI - In memoriam: Thomas Rogers Forbes (1911-1988). PMID- 2224179 TI - Optimization and application of particle beam high-performance liquid chromatography/mass spectrometry to compounds of pharmaceutical interest. AB - Particle beam high-performance liquid chromatography/mass spectrometry (HPLC/MS) parameters were optimized for the sensitive analysis of several drugs in agricultural products such as milk and tissue. Sensitivity of the particle beam interface was greatest for solvents with low heat capacities (methanol greater than acetonitrile greater than isopropanol greater than water). Furthermore, optimal sensitivity was obtained at low solvent flow rates (about 0.4-0.6 ml min 1). Parameters such as desolvation temperature, helium flow rate to the nebulizer and nebulizer position resulted in minimal change in sensitivity. The source temperature was optimized to obtain suitable vaporization with minimal thermal degradation (200-300 degrees C). The determination of a variety of compounds (including beta-lactams, cephapirin, tetracyclines, methylene blue, furosemide, spectinomycin, cytidine, 2-chloro-4-nitrobenzamide and thiamine) was possible using the particle beam interface. Under full-scan conditions, detection limits were in the 100 ng range for most drugs. With selected ion monitoring, particle beam HPLC/MS was demonstrated for the analysis of p.p.m. levels of these drugs in milk and tissue extracts. Precision of the particle beam analysis was usually better than 15% RSD. For the same compounds, HPLC/MS with a thermospray interface often resulted in less structural information (single ion spectra) then obtained by particle beam with thermospray detection limits varying from 10 ng to 1 microgram. PMID- 2224180 TI - Liquid chromatography/mass spectrometry of plasma glucose and secreted glucuronate for metabolic studies in humans. AB - Negative ion thermospray liquid chromatographic/mass spectrometric methods have been developed for the determination of isotopic enrichments for glucose and acetaminophen-uridine diphosphate glucuronate from (1-2H1)glucose, (1 2H1)galactose and (2-13C)acetate in humans. The error of estimate ranged from below 1% to 5%. The advantages of the method include fast analysis (up to 35 per hour), eased sample preparation, good precision, sensitivity comparable with gas chromatography/mass spectrometry and better than with isotope ratio mass spectrometry. PMID- 2224181 TI - Mixtures of porcine and bovine insulin analysed by fast atom bombardment mass spectrometry with selected ion monitoring. AB - Mixtures of bovine and porcine insulin have been analysed by fast atom bombardment mass spectrometry with selected ion monitoring of M + H ions at m/z 5733.9 (bovine) and 5778.0 (porcine). Porcine insulin could be detected in a mixture of 2% porcine and 98% bovine insulin and with bovine insulin as the minor component as little as 1% could be detected. PMID- 2224182 TI - In vitro metabolism of cannabigerol in several mammalian species. AB - Microsomal incubations were prepared from the livers of male mice, rats, cats, guinea-pigs, hamsters and gerbils and both male and female rabbits and were incubated with cannabigerol (CBG), a constituent of marihuana. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and examined as trimethylsilyl (TMS) and (2H9)TMS derivatives by gas chromatography/mass spectrometry. Structural elucidation was aided by hydrogenation of the metabolites to tetrahydro derivatives. Similar metabolites were produced by each of the species but the ratios of the individual compounds differed considerably. Twelve metabolites were identified. The major metabolites were monohydroxy compounds with the hydroxyl group at C-8', C-9', C-4' or at one of any position of the pentyl chain. Reduction of the delta-6' double bond was prominent in the cat to give 8'-hydroxy-6',7'-dihydro-CBG. The other major metabolic route was epoxidation of this double bond and hydrolysis to give 6',7' dihydroxy-6',7'-dihydro-CBG. Although epoxidation of the other double bond was detected, the resulting metabolite was present in low concentration and hydrolysis was not observed. The mass spectral fragmentation of CBG and its metabolites was dominated by formation of the tropylium ion by cleavage of the C 1'--C-2' bond and by ions formed by cleavage of the C-3'--C-4' and C-4'--C-5' bonds. In addition, compounds containing hydroxylation at C-1"--C-4" (pentyl chain) gave rise to the same abundant diagnostic ions that have been observed for corresponding metabolites of other cannabinoids. PMID- 2224183 TI - Measurement of stable isotopic enrichment of underivatized acetate by gas chromatography/mass spectrometry: application to in vivo estimation of acetate production. AB - In order to assess endogenous and colonic production of acetate, we have developed an assay for determining the isotopic enrichment of plasma acetate using gas chromatography/mass spectrometry (GC/MS). Acidified, deproteinized plasma (200 microliters) was extracted into ethyl ether, and the ether phase was then injected into a gas chromatograph/mass spectrometer fitted with a 30 m x 0.252 mm i.d. capillary column (temperature program 50-245 degrees C at 10 degrees C min-1). Using electron impact GC/MS and selected ion monitoring, peak areas of ions with m/z 60 and 61 (M + 1) were determined. Triplicate extractions of enriched plasma samples (mol.% excess 1.38-1.5%) resulted in a coefficient of variation of 1.6-5.9%. Unenriched plasma samples were found to have an enrichment close to theoretical natural abundance, and analysis of our (1-13C)acetate tracer (99 at.% excess) revealed an ion at m/z 61 and no ion at m/z 60. To verify accuracy, we conducted an in vivo isotope dilution study. In a 1-month-old piglet, fasted for 24 h, changing the rate of a 4 h infusion (mmol h-1) of (1 13C)acetate from 0.141 to 0.282 doubled the isotope enrichment (2.08 x) of the second plateau. The rate of appearance of acetate was 26.0 mumols kg-1 min-1, which is comparable to that reported in fasting sheep. PMID- 2224184 TI - In vitro metabolism of cannabidiol in the rabbit: identification of seventeen new metabolites including thirteen dihydroxylated in the isopropenyl chain. AB - The metabolism of cannabidiol (CBD) was studied in liver microsomes from the female New Zealand white rabbit. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and examined as trimethylsilyl (TMS), methyl ester/TMS and (2H9)TMS derivatives by gas chromatography/mass spectrometry. Thirty-nine metabolites, mainly mono-, di- and tri-hydroxy compounds, were identified; 17 of these have not been reported before. New metabolites included 8,9-dihydroxy-8,9-dihydro-CBD (two isomers) and seven monohydroxy derivatives of each of these two compounds. The mass spectra of the TMS derivatives of metabolites not hydroxylated in the isopropenyl group were generally dominated by the ion produced by retro-Diels-Alder cleavage of the terpene ring. Other structurally informative ions included the tropylium ion and fragments diagnostic of hydroxylation at C-1", C-2", C-3", C-4" and C-7. The spectra of the TMS derivatives of metabolites hydroxylated in the isopropenyl group were generally dominated by the ion at m/z 143. This involved loss of CH2OTMS and a retro-Diels-Alder fragmentation analogous to that seen in the other metabolites, but with charge retention by the other (smaller) fragment. Other, related fragment ions also characterized these metabolites. PMID- 2224185 TI - Fast atom bombardment mass spectrometric analysis of haemoglobin variants: use of V-8 protease in the identification of Hb M Hyde Park and Hb San Jose. AB - The characterization of two human haemoglobin variants, Hb M Hyde Park and Hb San Jose, by fast atom bombardment mass spectrometry is reported. The identification of the site and nature of the amino acid substitution was performed by analysis of the peptide mixture generated by proteolytic digestion of the variant beta globin chains with V-8 protease. The use of this protease was instrumental in the unambiguous identification of the replaced residues because the tryptic map alone was unable to unequivocally locate the modification. Spectra obtained were easily interpreted and the characterization of Hb M Hyde Park (beta, 92 Hys leads to Tyr) and Hb San Jose (beta 7 Glu leads to Gly) was accomplished essentially by the same procedure already described for the tryptic map. These results are suggestive of alternative approaches in haemoglobin variants characterization using different proteolytic enzymes when tryptic data alone do not lead to unambiguous results. PMID- 2224186 TI - Identification of cyclic metabolites of isopropylated phenyl phosphates in rabbit bile. AB - Some organophosphorous compounds, especially tri-o-cresylphosphate (TOCP), induce delay neuropathy. The cyclic saligenin phosphate (PSP) has been suggested to be the active metabolite of the protoxicant TOCP. The o-isopropylated triphenyl phosphates have been proven not to be neurotoxic. Studying the metabolism of these compounds we found the following cyclic metabolites: 2-phenyl-4H-4,4 dimethyl-1,1,3,2-benzodioxaphosphoran-2-oxide and 2-(o-isopropylphenyl)-4H-4,4 dimethyl-1,1,3,2-benzodioxaphospho ran-2-oxide. Additionally, monohydroxylated metabolites of the parent esters were detectable. The effect of glucuronidation on the formation of the cyclic metabolites is discussed in this paper. PMID- 2224187 TI - A selected ion monitoring method for quantifying simvastatin and its acid form in human plasma, using the ferroceneboronate derivative. AB - Simvastatin, a pro-drug lactone, forms the open carboxylic acid as a major metabolite that inhibits the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Simvastatin and the acid in plasma were quantified by a gas chromatography/mass spectrometry/selected ion monitoring (GC/MS/SIM) method. These drugs were separated by solid-phase extraction and independently converted into a 1,3-diol-type compound. This compound reacted with ferroceneboronic acid to yield the cyclic boronate that gave satisfactory mass spectra for GC/MS/SIM measurements. The serum was dominated by the molecular ion appearing as the base peak, thereby leading to a sensitive and selective assay. The calibration curves for simvastatin and the acid were linear in their concentration range of 0.1-10 ng ml-1, where the values of coefficient of variation for both drugs were below 8%, except for the value of 11% for simvastatin at a concentration of 0.1 ng ml 1. The quantification limit for both drugs was 0.1 ng ml-1 on the basis of a signal-to-noise ratio of 4:1. PMID- 2224188 TI - Bandits on the run: the oral snuff debate. PMID- 2224189 TI - Oral tobacco: prevalence, health risks, dependence potential and public policy. AB - This paper discusses public health policy with regard to oral tobacco use. It notes that in the UK, oral tobacco use is extremely rare. Concern that it might become prevalent among schoolchildren has proved unfounded. Smokeless tobacco almost certainly carries health risks but these risks are probably less than from smoking. What little evidence exists suggests that smokeless tobacco may be less dependence-inducing than cigarettes. In the light of this, the UK Government's decision to ban oral tobacco products is hard to reconcile with their continuing to permit the sale and advertising of cigarettes. A cynic would view the Government's ban as a 'no cost' measure to placate the public health lobby and ease the pressure for more restrictions on cigarette promotion. The inconsistency in the Government's approach to Skoal Bandits and cigarettes may be used as a focus for pressure to change in the laws governing promotion of cigarettes. PMID- 2224190 TI - Moist snuff in Sweden--tradition and evolution. AB - Snuff-dipping was already widespread in Sweden in the 19th century. After the 1920s snuff sales went down, but Sweden still kept its position as world leader in per capita consumption of moist snuff. Following a major advertising campaign snuff consumption began rising again in the late 1960s. The Swedish Tobacco Company claims that Swedish snuff is a 'less harmful' alternative to cigarettes. Swedish epidemiological studies indicate that there is a cancer risk from snuff dipping, but it is low compared with smoking. Accordingly, the STC claims to "do a good job replacing cigarettes with snuff". However, an analysis of the trends in tobacco usage patterns in Sweden during the last few decades does not support this claim. The marketing of moist snuff has not primarily attracted older smokers who would seek help in order to stop smoking, but young people. The use of snuff is no prerequisite and no guarantee for a decrease of smoking. On the contrary, taking up snuff must be seen as an introduction to the tobacco habit and possibly a first step towards taking up cigarettes. PMID- 2224191 TI - Being positive: drug injectors' experiences of HIV infection. AB - There is a growing concern within Britain, Europe and North America that injecting drug users may pose the greatest risk of transmitting HIV infection to the wider heterosexual non-drug injecting population. However, we know very little about the reactions of injecting drug users to the knowledge of being HIV positive and thus are hampered in our attempts at estimating the actual risks such individuals pose to others. This paper is based upon interviews with 26 seropositive injecting drug users and examines their experiences in relation to the following areas: (1) hearing the news; (2) communicating the diagnosis to others; (3) current drug use and sexual behaviour; and (4) perceptions of the future. It is shown that injecting drug users have a wide range of responses in relation to each of these areas and while the implications for their care and counselling are drawn out it is suggested that the fact of this variability undermines any single approach to patient or client management. PMID- 2224192 TI - AIDS-related risk behaviour, polydrug use and temazepam. AB - In a study of AIDS-related risk behaviour among injecting drug users in the north west of England it was found that 90% were polydrug users, and 28% were using temazepam. A third of all polydrug users had regularly used more than three drugs in addition to their preferred drug in the previous year. Statistical analysis revealed that the use of temazepam and extensive polydrug use were associated with sharing injecting equipment. Significant associations were also found with indices of sexual risk behaviour. It was concluded that multiple drug use and the use of temazepam were associated with behaviour that could increase exposure to HIV infection. PMID- 2224193 TI - Metyrapone-induced withdrawal symptoms. AB - The metyrapone test is widely used in endocrinological testing to assess the integrity of hypothalamic-pituitary-adrenal axis function; we have used it to study the metabolic basis of addictive disease and opioid dependence. In recent studies, we have observed that metyrapone administration in long-term methadone maintained patients and in patients undergoing slow dose reduction to drug-free status following chronic treatment may induce a narcotic withdrawal-like syndrome. Although metyrapone is known to produce mild adverse reactions in non opiate dependent subjects, narcotic withdrawal-like symptoms have not been previously observed or reported. The metyrapone test was administered to 15 former heroin addicts: 10 (8 male, 2 female) in steady-state methadone maintenance therapy (30 to 90 mg/d) and 5 (3 male, 2 female) in the final phase of a slow methadone dose reduction procedure (0 to 10 mg/d). Eight out of 15 methadone maintenance subjects exhibited a narcotic withdrawal-like syndrome ranging from 'moderate' to 'severe' and four additional subjects had 'mild' symptoms, occurring within 1 h after metyrapone administration, and resolving within 2 h of onset. No significant symptoms were seen in 3 methadone maintained subjects nor in any of 9 normal volunteers (7 male, 2 female). The mechanism by which metyrapone induces symptoms resembling narcotic withdrawal in opiate dependent individuals is unknown but physicians performing this test should be aware of this possible response. PMID- 2224194 TI - Familial transmission of alcohol use, III. Impact of imitation/non-imitation of parent alcohol use (1960) on the sensible/problem drinking of their offspring (1977). AB - Imitation/non-imitation by adult offspring of alcohol-related parent behavior was examined in the context of the 'fall-off effect' and of sensible/problem alcohol use, two processes which tend to constrain drinking. Evidence indicates there is more imitation by adult offspring of abstemious parents (both abstainer and low volume) than of high volume parents. Adult offspring drink significantly less, on the average, than their high volume parents, a phenomenon here termed 'fall-off effect' for both men and women with respect to either their fathers or mothers. This fall-off among social drinkers appears when the mother approaches or the father consumes at or more than a typical daily drinking level (greater than or equal to 1 drink per day). More sensible drinking occurs among adult offspring when (1) the parent has no drinking problem-signs than when the parent has drinking problems (this pattern appears at all levels of offspring consumption), and (2) when parents drink at high volume and have no problems for those offspring who do not imitate parent volume. Drinking 'sensibly' appears to be associated directly with the level of parent alcohol use and offsprings' own drinking levels (considered as imitation or non-imitation of parents), and indirectly with offspring recall of problematic intake by parents. Drinking sensibly is a medical, education and public health issue. PMID- 2224195 TI - Communicative competence in sons of alcoholics. AB - Sons of alcoholic (SA), depressive (SD), and social drinking (SN) fathers gave 3 min speeches under low- and high-stress conditions. Trained raters, unaware of group membership, scored each speech on a variety of communicative competence dimensions. The results gave evidence that the SA group, relative to the SN group, showed deficits in all six speech variables. Further results suggested that the SA group was unaffected by level of stress, while the SD group showed a decrease in communicative clarity from speech 1 (low stress) to speech 2 (high stress). The results suggest lower levels of communicative competence among adult sons of alcoholics. The implication of this finding with regard to the psychosocial functioning of children of alcoholics is discussed. PMID- 2224196 TI - Alcohol consumption and unemployment among men: the Scottish Heart Health Study. AB - There is growing concern about the relationship between health-related behaviour and employment status. Data from the Scottish Heart Health Study included information on the self-reported drinking habits of 4170 full-time employed and 479 unemployed men. This enabled the patterns of alcohol consumption in the unemployed to be compared to those of the full-time workers. There were appreciable differences in both frequency and quantity of reported alcohol consumption between the two groups and a higher percentage of the unemployed reported being non-drinkers. Nevertheless, the unemployed drinkers drank more alcohol than those in employment, even after standardization for both age and social class (27.9 units vs 20.7 units per week). Binge drinking was common in both groups, but the proportion was higher among the unemployed (58.8% of the unemployed reported drinking more than eight units in any day in the previous week compared to 33.5% among the full-time workers). In an attempt to validate these findings and to assess the possible health consequences of heavy drinking, serum gamma-glutamyltransferase levels were analysed. Overall, the unemployed were found to have higher levels, this finding being largely influenced by the excess of heavy drinkers. The reasons behind these differences in drinking behaviour between the employed and unemployed need to be identified before any cause and effect hypotheses can be generated, and counselling given where needed. PMID- 2224197 TI - How much alcohol is in a 'standard drink'? An analysis of 125 studies. AB - A group of researchers have undertaken a review of 125 international, published, epidemiological studies that relate various physical harms to different levels of alcohol consumption. For this review it was necessary to be able to compare the data from the different studies directly. The different measures of alcohol quoted in the studies were converted to the standard measure of grammes of alcohol. The present paper discusses the problems involved in doing this, and gives details of the conversion methods used. PMID- 2224198 TI - Assisted natural recovery from alcohol problems: effects of a self-help manual with and without supplementary telephone contact. AB - One hundred and seven problem drinkers responding to a newspaper advertisement were randomly assigned to groups receiving: (1) a general advice and information booklet; (2) a behaviourally-based self-help manual; (3) in addition to the manual, an opportunity to make progress reports to a telephone answering service; and (4) in addition to the manual, an opportunity to make telephoned progress reports to an interviewer. Eighty-seven (81.3%) respondents were successfully followed-up and collateral information was available for 54 (61.1%) of these. Results showed a higher proportion drinking above recommended limits at six months follow-up in the control group (78%) than in the groups receiving the manual (53%). There were no significant differences due to presence or type of telephone contact and poor use was made of the opportunity for telephone contact. Findings justify the widespread promotion of self-help materials as a means of assisting the natural recovery process among problem drinkers. PMID- 2224199 TI - Inebriate institutions in North America, 1840-1920. AB - This paper analyses two contemporaneous types of 19th-century North American inebriate institutions and attempts by their promoters to develop a public treatment system. Inebriate 'homes' or 'retreats' descended from a tradition of therapeutic temperance that originated in the Washingtonian Movement of the 1840s. They were small, urban, private and charitable, dedicated to voluntaristic and Christian principles, and were intimately connected with local temperance groups that provided support after residential treatment. Inebriate asylums took inspiration from insane asylums and were large, public, coercive and isolated in rural areas. Their promoters were steeped in the deterministic, hereditarian neurologism of Victorian psychiatry. Asylum enthusiasts dominated the public treatment movement, but developed a largely disciplinary and custodial vision that undermined their political appeal. As inebriate asylums could not easily be distinguished from insane asylums, almshouses or jails, legislators regarded them as superfluous and very few were established. Prohibition destroyed what public inebriate institutions existed. Inebriate colonies, usually connected with county jails, were the only survivors of the 19th-century treatment movement apart from private sanitaria and a few inebriate wards in city or county hospitals. PMID- 2224201 TI - ICAA Berlin. PMID- 2224202 TI - UK: MRC AIDS research 1990. PMID- 2224200 TI - Dynamics and dilemmas in a DDU. PMID- 2224203 TI - Hypocalcemia in cancer. AB - Hypocalcemia based on total calcium measurement is frequent in certain cancers (especially prostate) in association with osteosclerotic bone metastases. In a majority of these patients hypocalcemia is related to the low serum albumin and/or renal failure. True ionized hypocalcemia may be seen as a toxic effect of certain chemotherapeutic agents or as a consequence of hyperphosphatemia due to rapid tumor lysis. In addition, tumors may produce osteoblast-stimulating factor(s) which cause massive accretion of calcium by the skeleton. Isolation and purification of these factors may provide us with unique osteoblast-stimulating factors which may have therapeutic applications. PMID- 2224204 TI - Collagen synthesis and mineralization in the early phase of distraction bone healing. AB - Corticotomy of the distal radius followed by gradual distraction by external fixation was performed on three sheep. Collagen synthesis and mineral deposition were analysed from sequential biopsies obtained from the center of the distraction area during the first 4 weeks of distraction. The whole distraction area was rapidly filled with organic matrix the amount of which, due to fluctuation in its nonprotein component, initially decreased from 88 to 66% of the level in control bone but gained its initial level in 4 weeks. Total protein in the matrix represented 70% of that in the control bone during the 4-week follow up period while the proportion of collagen of the total protein increased from 53 to 88%, a level comparable with the unoperated bone. Determination of the type of fibrillar collagen by characterization of their cyanogen bromide peptides showed that in the distraction area production of type II collagen does not occur but the heteropolymer type I (alpha 1(I)2 alpha 2(I)1) collagen represents almost totally the collagen synthesized. Deposition of mineral into the distraction gap was detectable already after 2 weeks and increased rapidly after 3 weeks of distraction. The results suggest that unlike in other processes, e.g., direct osteonal and callus-type bone repair, in distraction bone healing gradual distraction of osteotomized bone leads directly to synthesis of mature fibrous organic matrix of bone followed by its rapid mineralization. PMID- 2224205 TI - Histomorphometry of iliac crest bone in 346 normal black and white South African adults. AB - We examined undecalcified transiliac bone samples from 346 normal black and white South African adults (age range 21-83 years) by routine histomorphometry. The results were analysed for race-, age- and sex-dependent characteristics of trabecular microstructure (bone volume, trabecular thickness, trabecular number, trabecular separation) and static bone turnover variables (osteoid surface, osteoid volume, osteoid thickness, erosion surface). Trabecular thickness was greater in blacks than in whites, and bone volume was greater in black males, but not in black females, than in their white counterparts. Values for osteoid surface, volume and thickness, and for erosion surface were greater in blacks than in whites. Age-related changes were: a decline in bone volume in all race/sex groups; a decline in trabecular thickness in all groups except black males; a decline in trabecular number in all groups except black females; and a rise in trabecular separation in all groups except black females. There was an increase with age in osteoid surface in all groups except white males, in osteoid volume in all groups, and in erosion surface in blacks only. When correcting for age there were no sex-dependent differences in microstructure but values of some osteoid variables were greater in males than in females. If the greater osteoid and erosion values in blacks reflect greater bone turnover, then trabecular bone in blacks would be renewed more frequently, be subjected to fewer loading cycles and be less prone to fatigue failure. Blacks may thus have trabecular bone of better quality and sturdier microarchitecture. These features could contribute to the lower spontaneous fracture rate in blacks. PMID- 2224206 TI - Bone mineral content of Gambian and British children aged 0-36 months. AB - The influence of age, sex and body size on the bone mineral content of the radius (BMC) measured by single-photon absorptiometry has been studied in 134 British and 243 rural Gambian children aged 0-36 months. Growth rates and childhood nutrition, including calcium intakes, were markedly different in the two communities. In both groups BMC increased with age and was higher in boys (8%, P less than 0.001). Adjustment for body size (height, weight, bone width), using multiple regression analysis, removed the age effect and reduced the sex difference to 4% (P less than 0.01). Gambian children had significantly lower BMCs than British children of the same age (P less than 0.001), averaging 11% close to birth and diverging to a calculated difference of 31% at 36 months. The differential was reduced after adjustment for body size but remained significant (P less than 0.01) with BMC values diverging from birth to a predicted difference of 12% at 15 kg body weight. The extent to which these results reflect the low calcium intakes of Gambian children requires further study. PMID- 2224207 TI - Stimulation of bone resorption and cell proliferation in vitro by human gingival fibroblasts from patients with periodontal disease. AB - In the present communication we report that fibroblasts, isolated from human gingiva obtained from 13 different patients, secreted soluble product(s) which can promote bone resorption in vitro. Fibroblasts were isolated from explants of human gingiva, subcultured, grown to confluent monolayers, subsequently cultured in growth arrest media for 0-72 h and conditioned media harvested. Bone resorption was assessed in cultured mouse calvarial bone by quantifying the mobilization of minerals and the release of lysosomal enzymes. Human fibroblast conditioned media (HFCM) dose-dependently stimulated the release of 45Ca from prelabelled bones and the mobilization of stable calcium and inorganic phosphate from unlabelled bones. In addition, HFCM increased the release of beta glucuronidase and beta-N-acetylglucosaminidase from the calvaria. No effect of HFCM on the release of 45Ca from dead bones could be seen. HFCM caused a dose dependent increased degradation of bone matrix proteins, as assessed by the release of 3H from [3H]proline-labelled calvaria. The stimulation of 45Ca release could already be seen after 3-12 h of treatment. Treatment of the bones with HFCM for 12 h was sufficient to obtain a prolonged stimulation of 45Ca release. Bones cultured in the presence of HFCM showed an increased number of osteoclasts. Calcitonin, but not indomethacin, inhibited 45Ca release stimulated by HFCM. Ultrafiltration of HFCM did not cause any loss of the 45Ca release response. The amount of bone-resorbing activity produced by the gingival cells was proportional to the number of cells. In addition, HFCM stimulated the proliferation of human fibroblasts and osteoblast-enriched mouse calvarial bone cells. It is concluded that human gingival fibroblasts secrete one or several factors that can stimulate osteoclastic bone resorption in vitro by a prostaglandin-independent pathway. PMID- 2224208 TI - Bone mineral mass associated with postmenopausal vertebral deformities. AB - Vertebral morphometry on thoracic and lumbar spine radiographs and bone mass measurements were carried out on 215 patients investigated for postmenopausal osteoporosis. Bone mineral mass was measured on the central third of the skeleton by neutron activation analysis and the result, normalized for body size, expressed as a calcium bone index (CaBI). The normal CaBI value for females (20 40 years) is 0.97 (0.11) with a lower limit for these young, normal women, of 0.75. Vertebral compression deformity was defined as a mean height more than 15% lower than adjacent normal vertebrae. Thoracic and lumbar anterior wedge deformities and central compression were defined as anterior/posterior (A/P) or mid/posterior (M/P) height ratios of less than 0.75. For the 129 patients without vertebral deformities, the mean CaBI was 0.80 (0.12) (1 SD) and 32% of these patients had CaBI values below the normal young adult range (CaBI less than 0.75). In 20 patients, vertebral deformities were limited to 1 or 2 mid-thoracic vertebrae, and the mean CaBI values for these 20 patients was 0.81 (0.15), equal to that for patients without any vertebral deformity. For the remaining 67 patients, (i.e., patients with one or more vertebral deformities involving at least one distal thoracic or one lumbar vertebra) the mean CaBI value was 0.66 (0.10), 17% below the value for patients without vertebral deformities. Low CaBI values (CaBI less than 0.75) were observed in 87% of these patients, consistent with the diagnosis of osteoporotic fractures. Based on our CaBI results, however, mid-thoracic deformity was not associated with significant osteopenia and is not, therefore, diagnostic of osteoporotic fracture. PMID- 2224209 TI - Abstracts of the 5th Sydney Bone Symposium. Sydney, 23-25 April 1990. PMID- 2224210 TI - Abstracts of the 1st annual scientific meeting of the Australian and New Zealand Bone and Mineral Society. Perth, 26-27 September 1990. PMID- 2224211 TI - Influenza vaccination and the elderly. PMID- 2224212 TI - Vasectomy and the human testis. PMID- 2224213 TI - Hirsutism. PMID- 2224214 TI - The epidemiology of malpractice. PMID- 2224215 TI - Interventions in chronic renal failure. PMID- 2224216 TI - Sodium-lithium countertransport activity in red cells of patients with insulin dependent diabetes and nephropathy and their parents. AB - OBJECTIVE: To determine whether there are familial and genetic aspects of sodium lithium countertransport activity in red cells in diabetic nephropathy. DESIGN: Case-control study. SETTING: Teaching hospital diabetic clinic. SUBJECTS: 40 Patients with insulin dependent diabetes, both of whose parents were alive: 20 with persistent proteinuria and 20 with normal albumin excretion matched for age, duration of diabetes, and body mass index. All 80 parents. MAIN OUTCOME MEASURES: Sodium-lithium countertransport activity in red cells and arterial blood pressure. RESULTS: Sodium-lithium countertransport activity in red cells was higher in the patients with proteinuria than in the patients with normoalbuminuria (mean (95% confidence interval) 0.47 (0.39 to 0.54) v 0.33 (0.28 to 0.38) mmol/l red cells/h respectively, p = 0.0036; mean difference 0.14 (0.04 to 0.22)). The mean countertransport activity for the two parents of each patient was calculated, and from this the mean value for each group of parents was calculated; the value was higher in the parents of the patients with proteinuria than in the parents of the patients with normoalbuminuria (0.40 (0.32 to 0.48) v 0.30 (0.26 to 0.33) mmol/l red cells/h respectively, p = 0.016; 0.10 (0.02 to 0.19)). Twenty-eight of the parents of the patients with proteinuria compared with 12 of the parents of the patients with normoalbuminuria had a countertransport activity that was above the median value in all 80 parents (p less than 0.001). Mean arterial blood pressure in the parents of the patients with proteinuria was related to that of their offspring (r = 0.46; p less than 0.01). There was a positive correlation between the sodium-lithium countertransport activity in red cells in the parents and their offspring when all parents and patients were considered (r = 0.37; p less than 0.001). CONCLUSIONS: Increased sodium-lithium countertransport activity in red cells in the parents of diabetic patients with nephropathy provides further evidence that familial, and possibly genetic, factors related to a predisposition to arterial hypertension have a role in the susceptibility of diabetic renal disease. PMID- 2224217 TI - Prediction of hip fracture in elderly women: a prospective study. AB - OBJECTIVE: To assess the relative importance of osteoporosis of the os calcis, cognisance, and mobility in the risk of subsequent fracture of the hip in elderly women. DESIGN: Prospective study of elderly women in residential care over two years. SETTING: 21 Private or 38 local authority residential homes for the elderly and 4 geriatric hospitals in Doncaster and Hull. SUBJECTS: 1414 Ambulant women aged over 69, in private or local authority residential care or geriatric care. Those who had had bilateral hip surgery were excluded. MAIN OUTCOME MEASURES: Broad band ultrasonic attenuation (BUA) index, Clifton assessment procedures for the elderly test (for cognisance), and mobility on a six point scale, and fracture of the hip in the subsequent two year period. RESULTS: 73 Women fractured their hip during the two years. Their mean age was not significantly different from that of the women who did not have a fracture (85.3 (SD 5.6) v 83.9 (6.3); p = 0.07), but their mean BUA index (40.3 (19.3) v 50.9 (22.2) db/MH2), and score for cognisance (median 19 (interquartile range 10.5 27.0) v 24 (17-30)) were significantly lower (both p less than 0.001). These variables had independent associations with fracture of the hip. Women with fractures had a significantly lower score for the psychomotor component of the cognisance test (4.5 (1-8) v 7 (2-10); p less than 0.0025 and were significantly more mobile (1(1-3) v 3 (1-6); p less than 0.02). Subdividing women according to high, medium, and low scores for BUA index and cognisance testing disclosed a high risk group (118 women) with low BUA index and cognisance score, whose incidence of fracture was 12.8%; in the group at lowest risk (136 women) with high BUA index and cognisance score, the incidence of fracture was only 1.5% (relative risk 8.4 (95% confidence interval -2.0 to 35.5]. Further analysis showed that those most at risk were, additionally, most mobile but that less mobile women with good cognisance had a low incidence of fractures, regardless of the BUA index, (1.2%, high index, v 0.9%, low index). CONCLUSIONS: Elderly women most at risk of sustaining hip fractures were those with low BUA index, low cognisance test score, and high mobility. Improving bone strength and cognisance in elderly women may reduce their incidence of hip fracture. PMID- 2224218 TI - Four and a half year follow up of women with dyskaryotic cervical smears. AB - OBJECTIVE: To determine the proportion of women with mild or moderate dyskaryosis in cervical smears who (a) progress to cervical intraepithelial neoplasia grade III or worse or (b) regress. DESIGN: Four and a half year cytological follow up study of women with mild or moderate dyskaryosis in cervical smears. SETTING: 666 Women (mean age 28 (SD 8) years; range 14-74) found to have borderline, mild, or moderate dyskaryosis on routine screening. RESULTS: 45 Women (6.8%) had a cone biopsy recommended on the basis of an abnormal follow up smear (severe dyskaryosis suggestive of cervical intraepithelial neoplasia grade III or invasive cancer), and in one patient cervical intraepithelial neoplasia grade III was reported in a biopsy specimen after dilatation and curettage. Life table analysis gave a 14% probability of a patient being recommended for a biopsy after four and a half years of follow up (95% confidence interval 12% to 15%). There was a significant excess incidence of invasive cancer of the cervix in the series compared with the general population (five cases observed compared with less than 0.1 expected). 157 Patients (24%) showed reversion to a normal cell pattern sustained in several smears over more than 18 months but a single negative smear was an unreliable indicator of apparent regression. Having two successive smears showing mild dyskaryosis or a smear at any time showing moderate dyskaryosis was a significant predictor of a subsequent severely dyskaryotic smear. CONCLUSIONS: Women found to have mild or moderate dyskaryosis in cervical smears should be kept under regular surveillance. The optimum management of these patients--by cytology or colposcopy--needs to be determined by randomised controlled trials. PMID- 2224219 TI - Why costs of consultations in general practice vary. PMID- 2224220 TI - Effectiveness of eye protection in the metal working industry. PMID- 2224221 TI - Differences in disability between people with mental handicaps who were resettled in the community and those who remained in hospital. PMID- 2224222 TI - Consultation rates among middle aged men in general practice over three years. AB - OBJECTIVE: To provide data on consultation rates in general practice for middle aged men over three years according to their age and social class. DESIGN: Prospective study of men over eight years. Data on consultation rates during years 6-8 were collected retrospectively from practice records. SETTING: Over 1000 general practices in Great Britain by year 8. Initially (in 1978-80) the men had been selected at random from one practice in each of 24 towns. SUBJECTS: 7013 Men aged 46-65 in the sixth year of follow up. MAIN OUTCOME MEASURE: Number of consultations a year over three years. RESULTS: The mean annual consultation rate over the three years rose steadily with age (7.0 at age 46-50 to 9.7 at age 61 65) and with social class (6.4 in class I to 10.0 in class V) but was potentially misleading as the distribution was skew: 10.5% of men (736) did not consult over the three years and 17.2% (1209) consulted only once or twice, whereas 11.4% (798) of men were seen more than 18 times. The percentage of men who did not consult over three years fell only slightly with age and was unrelated to social class, with roughly a tenth of all age and social class groups not consulting. Two thirds of non-consulters in year 6 (1598/2334) consulted in year 7 or 8. CONCLUSIONS: The mean is not an appropriate summary measure of consultation rates and may conceal important differences among practices or other groups. The new general practitioner contract stipulates that all patients aged 16-74 must be provided with information to promote health and prevent illness at least once every three years. Most practices will have to approach a tenth of their men aged 46-65 specially to provide this service even if one consultation in three years is regarded as sufficient to allow a service to be provided. PMID- 2224223 TI - Mucocutaneous leishmaniasis. PMID- 2224224 TI - ABC of major trauma. Transport of injured patients. PMID- 2224225 TI - Crisis in admission beds. PMID- 2224226 TI - Effect of erythropoietin in patients with myeloma. PMID- 2224228 TI - Referral letters and replies from orthopaedic departments. PMID- 2224227 TI - Rectal examination in general practice. PMID- 2224229 TI - Dystonic dysphagia associated with fluspirilene. PMID- 2224230 TI - Captopril and systemic lupus erythematosus syndrome. PMID- 2224232 TI - One hand clapping. PMID- 2224231 TI - Inhibitors of hydroxymethylglutaryl coenzyme A reductase for treating hypercholesterolaemia. PMID- 2224233 TI - What future for the BMA? PMID- 2224234 TI - Medicine's need for kaizen. PMID- 2224235 TI - Looking at the pictures. PMID- 2224236 TI - The population bomb has exploded already. PMID- 2224237 TI - Reflections on the changing times. PMID- 2224238 TI - The movement towards the professionalization of medicine. PMID- 2224239 TI - Medicine as a profession: times of change. PMID- 2224240 TI - The evolution of the NHS. PMID- 2224241 TI - The state and the profession: the politics of the double bed. PMID- 2224242 TI - The new new general practice: the changing philosophies of primary care. PMID- 2224244 TI - 120 years on: voices on child abuse. PMID- 2224243 TI - Ernest Hart and the social thrust of Victorian medicine. PMID- 2224245 TI - Medical men and military matters: the BMJ and the Victorian army. PMID- 2224246 TI - Medicine in the armed services. PMID- 2224247 TI - The rise of the British pharmaceutical industry. PMID- 2224248 TI - Development of a rational practice of therapeutics. PMID- 2224249 TI - The BMJ and poverty. PMID- 2224250 TI - How soon is now? Public health and the BMJ. PMID- 2224251 TI - A toast to the BMJ. PMID- 2224252 TI - Marking times. PMID- 2224254 TI - Hugh Clegg: recollections of a great editor. PMID- 2224253 TI - The "top 50": a perspective on the BMJ drawn from the Science Citation Index. PMID- 2224256 TI - World medicine. A sort of obituary. PMID- 2224255 TI - Journalology--or what editors do. PMID- 2224257 TI - Rediscoveries. PMID- 2224258 TI - Guidelines for the management of asthma in adults. PMID- 2224259 TI - Oxalate, livers, and kidneys. PMID- 2224260 TI - Milk for babies and children. PMID- 2224261 TI - Diagnosing cancer of the pancreas. PMID- 2224263 TI - European meeting on HIV testing. PMID- 2224262 TI - Justice versus equity for haemophiliacs with AIDS. PMID- 2224264 TI - Getting an AIDS vaccine to the developing world. PMID- 2224265 TI - Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation: no causal relation with diabetic autonomic neuropathy. AB - OBJECTIVE: To examine the traditional view that unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation in insulin dependent diabetes mellitus are manifestations of autonomic neuropathy. DESIGN: Perspective assessment of unawareness of hypoglycaemia and detailed assessment of autonomic neuropathy in patients with insulin dependent diabetes according to the adequacy of their hypoglycaemic counterregulation. SETTING: One routine diabetic unit in a university teaching hospital. PATIENTS: 23 Patients aged 21-52 with insulin dependent diabetes mellitus (seven with symptoms suggesting autonomic neuropathy, nine with a serious clinical problem with hypoglycaemia, and seven without symptoms of autonomic neuropathy and without problems with hypoglycaemia) and 10 controls with a similar age distribution, without a personal or family history of diabetes. MAIN OUTCOME MEASURES: Presence of autonomic neuropathy as assessed with a test of the longest sympathetic fibres (acetylcholine sweatspot test), a pupil test, and a battery of seven cardiovascular autonomic function tests; adequacy of hypoglycaemic glucose counterregulation during a 40 mU/kg/h insulin infusion test; history of unawareness of hypoglycaemia; and response of plasma pancreatic polypeptide during hypoglycaemia, which depends on an intact and responding autonomic innervation of the pancreas. RESULTS: There was little evidence of autonomic neuropathy in either the 12 diabetic patients with a history of unawareness of hypoglycaemia or the seven patients with inadequate hypoglycaemic counterregulation. By contrast, in all seven patients with clear evidence of autonomic neuropathy there was no history of unawareness of hypoglycaemia and in six out of seven there was adequate hypoglycaemic counterregulation. Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation were significantly associated (p less than 0.01). The response of plasma pancreatic polypeptide in the diabetic patients with adequate counterregulation but without autonomic neuropathy was not significantly different from that of the controls (change in plasma pancreatic polypeptide 226.8 v 414 pmol/l). The patients with autonomic neuropathy had a negligible plasma pancreatic polypeptide response (3.7 pmol/l), but this response was also blunted in the patients with inadequate hypoglycaemic counterregulation (72.4 pmol/l) compared with that of the controls (p less than 0.05). CONCLUSIONS: Unawareness of hypoglycaemia and inadequate glucose counterregulation during hypoglycaemia are related to each other but are not due to autonomic neuropathy. The blunted plasma pancreatic polypeptide responses of the patients with inadequate hypoglycaemic counterregulation may reflect diminished autonomic activity consequent upon reduced responsiveness of a central glucoregulatory centre, rather than classical autonomic neuropathy. PMID- 2224266 TI - Postoperative analgesic requirements in patients exposed to positive intraoperative suggestions. AB - OBJECTIVE: To establish whether positive suggestions given to a patient under general anaesthesia reduce postoperative pain and analgesic requirements. DESIGN: Prospective double blind randomised study. SETTING: Operating theatre and gynaecology ward of a teaching hospital. PATIENTS: 63 Woman undergoing elective abdominal hysterectomy were randomised to be played either a tape of positive suggestions or a blank tape during the operation through a personal stereo system. INTERVENTIONS: Three women were withdrawn from the study. Anaesthesia was standardised for all of the women. Postoperative analgesia was provided through a patient controlled analgesia system for the first 24 hours. Pain scores were recorded every six hours. MAIN OUTCOME MEASURES: Morphine consumption over the first 24 hours after the operation; pain scores. RESULTS: Mean morphine requirements were 51.0 mg (95% confidence interval 42.1 to 60.0 mg in the women played positive suggestions; and 65.7 mg (55.6 to 75.7 mg) in those played a blank tape. The point estimate (95% confidence interval) for the difference of means was 14.6 mg (22.4%) (1.9 (2.9%) to 27.3 mg (41.6%] (p = 0.028). Pain scores were similar in the two groups. CONCLUSION: Positive intraoperative suggestions seem to have a significant effect in reducing patients' morphine requirements in the early postoperative period. PMID- 2224268 TI - Widespread cerebral ischaemia treated with nimodipine in a patient with eclampsia. PMID- 2224267 TI - Bone mineral loss in young women with amenorrhoea. AB - OBJECTIVE: To examine the impact of amenorrhoea on bone mineral density in women of reproductive age. DESIGN: Cross sectional study of 200 amenorrhoeic women compared with normally menstruating controls. SETTING: Teaching hospital outpatient clinic specialising in reproductive medicine. SUBJECTS: 200 Women aged 16-40 with a past or current history of amenorrhoea from various causes and of a median duration of three years, and a control group of 57 age matched normal volunteers with no history of menstrual disorder. MAIN OUTCOME MEASURE: Bone mineral density in the lumbar spine (L1-L4) as measured by dual energy x ray absorptiometry. RESULTS: The amenorrhoeic group showed a mean reduction in bone mineral density of 15% (95% confidence interval 12% to 18%) as compared with controls (mean bone mineral density 0.89 (SD 0.12) g/cm2 v 1.05 (0.09) g/cm2 in controls). Bone loss was related to the duration of amenorrhoea and the severity of oestrogen deficiency rather than to the underlying diagnosis. Patients with a history of fracture had significantly lower bone density than those without a history of fracture. Ten patients had suffered an apparently atraumatic fracture. CONCLUSIONS: Amenorrhoea in young women should be investigated and treated to prevent bone mineral loss. Menopausal women with a past history of amenorrhoea should be considered to be at high risk of osteoporosis. PMID- 2224269 TI - Should general practitioners call patients by their first names? AB - OBJECTIVE: To assess the acceptability to patients of the use of patients' first names by doctors and doctors' first names by patients in general practice. DESIGN: An administered questionnaire survey. SETTING: 5 General practices in Lothian. PATIENTS: 475 Patients consulting 30 general practitioners. MAIN OUTCOME MEASURE: Response by patients to questionnaire on attitude to use of first names. RESULTS: Most of the patients either liked (223) or did not mind (175) being called by their first names. Only 77 disliked it, most of whom were aged over 65. Most patients (324) did not, however, want to call the doctor by his or her first name. CONCLUSIONS: General practitioners should consider using patients' first names more often, particularly with younger patients. PMID- 2224270 TI - Screening children from overseas for infections: is it justified? AB - OBJECTIVES: To investigate current practice of screening children from abroad for infections after coming to the United Kingdom, and to make recommendations for future practice. DESIGN: A review of literature and a questionnaire sent to all health authorities and boards in the United Kingdom. SETTING: All health authorities and boards in the United Kingdom. SUBJECTS: 167 Health authorities or boards that completed questionnaires (response rate 80%), 59 of which used a screening programme. MAIN OUTCOME MEASURE: Response to questionnaire on policies for screening children for infections on their return from overseas. RESULTS: 12 Of the 59 authorities screened all children and one screened only those from the West Indian subcontinent. 13 Authorities excluded children from school while awaiting results; 58 screened for tuberculosis and four for diphtheria. CONCLUSIONS: There is a wide variation in screening policies around the country with no national consensus. Screening for diphtheria, typhoid, and salmonellosis is hard to justify and is probably not effective. Screening for tuberculosis, however, is supported by many authorities, is widely practised, and probably is effective. There is a strong case for rationalisation of screening. PMID- 2224273 TI - Surely a natural cancer remedy can't be dangerous. PMID- 2224271 TI - Invasive aspergillosis in immunosuppressed patients: potential hazard of hospital building work. PMID- 2224272 TI - ABC of major trauma. Radiological assessment--I. PMID- 2224274 TI - Lowering cholesterol concentrations and mortality. PMID- 2224275 TI - Hereditary (primary) haemochromatosis. PMID- 2224276 TI - Symptoms of low blood pressure. PMID- 2224277 TI - Choice cuts for patients with AIDS? PMID- 2224278 TI - Caseload or workload? PMID- 2224279 TI - How easy is it to contact the duty doctor responsible for admissions? PMID- 2224280 TI - Interpretation and management of PACT (prescribing analysis and cost) data on formularies. PMID- 2224281 TI - Ciprofloxacin and myasthenia gravis. PMID- 2224282 TI - Interaction between fluconazole and rifampicin. PMID- 2224283 TI - Analysis of binary trees when occasional multifurcations can be considered as aggregates of bifurcations. AB - The geometrical properties of neurons are important for the way they function within neural circuits. The arborescent processes of neurons that are necessary for the transmission of the information are formed by branching and elongation of segments. In studies that model the outgrowth the tree structures have generally been considered as binary. However, multifurcations do occur. It will be shown that if the multifurcations can be considered as aggregates of bifurcations they may be included in the topological analysis of neuronal branching patterns. PMID- 2224286 TI - International Collegium of Rehabilitative Audiology. PMID- 2224285 TI - Comparison of isoeffect relationships in radiotherapy. AB - Irradiation affects numerous physiological processes within cells and tissues and can lead to damage or death. If the damage is not too severe, cells have the ability to repair and regenerate. Many small injuries are repaired more easily than ones causing extensive damage and, consequently, tissues typically respond differently to one large dose of radiation than to many small doses, separated in time. In the radiotherapy of tumors, the choice of the fractionation regimen of dose over time is therefore as crucial as the total radiation dose. The interdependence between total dose, fractionation regimen, and radiation effect has been described mathematically with various isoeffect relationships. These relationships appear to be fundamentally distinct and have been considered unrelated; some even claim that one class of isoeffect relationships is appropriate whereas other relationships are rather useless. We examine how alternative isoeffect models relate to each other and test the reliability of estimating parameter values of one model from the other. PMID- 2224284 TI - Starvation survival and body composition in mammals with particular reference to Homo sapiens. AB - A computer model of body mass and composition in relation to gross energy balance is constructed. The model is built using conventional empirical physiological formulae rather than statistical or analytical mathematical techniques. The model is applied to the Minnesota and other experiments and produces as good or better simulations of observed values of changes in body weight than reported for other formulae or models. Alternative physiological mechanisms concerning metabolic adaptions to starvation, changes in time activity budgets and the energy equivalents of weight loss offer equally good simulations of experimental results. The present analysis highlights the survival value of a basal metabolic depression during starvation and indicates an optimal body composition of 10% mobilizable fat for starvation survival for a 70 kg man. Proper quantification of the effects of the physiological mechanisms involved depends on new experimental data, however. Long term continuous monitoring of time activity budgets are a necessary part of such experiments. PMID- 2224287 TI - Transition from pre-linguistic to linguistic communication in hearing-impaired infants. AB - This paper examines the development of the ability to signal intentionality in hearing-impaired infants. Four infants were monitored from the time aids were accepted and worn consistently until an expressive vocabulary of ten words was recorded. The focus of the study was the child's developing ability to coordinate attention to both a person and an object. Longitudinal video-taping allowed analysis of the stages and rate at which these infants achieved this pattern of attention. These infants were found to follow a sequence of steps similar to that reported in studies of hearing children. This finding and its possible implications for early identification of hearing impairment are discussed. PMID- 2224288 TI - Comparison of hearing aids and cochlear implants in profoundly and totally deaf persons. AB - Cochlear implants are increasingly used in the rehabilitation of the profoundly and totally deaf. Usually, insufficient gain of speech discrimination with a powerful conventional hearing aid is considered as a prerequisite for a cochlear prosthesis. With recent improvements of electronic systems, the criterion for this decision may change. To keep pace with the technical progress, a battery of speech sound tests suited for minimal auditory capabilities (MAC-battery) was developed and applied to groups of patients fitted with conventional instruments and with two different types of cochlear implants. Based on the comparison of the MAC-battery results of hearing aid groups, with the average performance of an implanted group, most conventionally fitted regular users of hearing aids should not be considered as candidates for cochlear implantation. The MAC-battery, although not a strictly standardized procedure, is a useful instrument for patient counselling and for the selection of implant candidates. PMID- 2224289 TI - Measures for the assessment of hearing aid provision and rehabilitation. AB - To determine the effectiveness of the provision of a hearing aid, some measure of benefit is desirable. Direct determination of benefit is difficult, not least due to the problems inherent in defining what benefit actually is. An alternative approach is to assess aspects of hearing aid use of performance that relate to benefit. Hours of daily use, satisfaction and self-rated performance are measures that might be expected to relate to benefit. The studies reported in this paper examine the relevance and repeatability of these measures. It is concluded that this three-parameter approach provides a simple, relevant and useful way of assessing benefit from amplification which has application in both individual and group studies. PMID- 2224291 TI - Digital/programmable hearing aids--an eye towards the future. PMID- 2224290 TI - Clinical trials with a programmable hearing aid set for various listening environments. AB - A conventional hearing aid has a frequency response that does not change much at normal listening levels. It is therefore unlikely that optimal speech intelligibility and optimal listening comfort can be obtained simultaneously, or in different listening environments. With a programmable hearing aid with multiple memories the listener can choose between a range of sound pictures, which increases the chance of finding a suitable frequency curve for each listening situation. The programmable hearing aid with eight separate settings stored in eight memories, was compared with personal hearing aids fitted according to the recommendations of the National Acoustic Laboratories (NAL) by 22 experienced hearing aid users. One memory of the programmable hearing aid was initially fitted according to the NAL recommendation. The other memories were programmed to give variations around that recommendation. One aim was to investigate whether the hearing-impaired user took advantage of different frequency responses to achieve listening improvements in acoustically different environments. Another aim was to evaluate the ergonomic and acoustical features of the programmable hearing aid, compared with other well fitted hearing aids. The evaluations were based on comparisons of the test hearing aid to the personal aid for each subject, looking at speech tests, direct paired comparison judgements, sound quality judgements and interviews. A majority of the subjects experienced substantial benefit from being able to use different frequency response curves in different environments. With the test hearing aid the subjects performed better in speech discrimination tests in noise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224292 TI - The reluctance to acknowledge hearing difficulties among hearing-impaired workers. AB - The reluctance to acknowledge hearing difficulties was studied with two groups of hearing-impaired workers and their spouses. One investigation involved a group interview with workers who participated in a pilot rehabilitation programme and who experienced the disclosure of their hearing difficulties to others by being the subject of a newspaper story on occupational deafness. Analysis of the transcript showed that they were strongly stigmatized as being deaf especially by co-workers. In a second investigation, interviews conducted with hearing-impaired workers who have had no previous contact with hearing specialists were analysed. A selection was made of the interviews containing several examples of contradiction in the worker's discourse or between the worker and his wife about the experience of hearing difficulties. The reluctance to acknowledge hearing difficulties was expressed through various forms of denial, minimization of the problem, uneasiness in talking about the problem and in attempts to normalize oneself. All these expressions can be found in the same individual's discourse. It is concluded that reluctance to acknowledge hearing difficulties is part of an adaptive process that should be taken into account in rehabilitative interventions. It also calls for interventions that would prevent hearing people from stigmatizing hearing-impaired people. PMID- 2224293 TI - The active fitting (AF) programme of hearing aids: a psychological perspective. AB - Rehabilitation of the majority of hearing handicapped in Sweden consists of hearing aid fitting, provision of technical devices and information during about four visits to a Hearing Centre. Generally there is no structured guidance of the hearing handicapped on how to proceed with the hearing aid at home between appointments. A programme of active fitting (AF) of hearing aids, with a task oriented diary, 'Try Your Hearing Aid' as a basic part, was therefore developed. We conducted a series of studies from 1985 to 1988 with the aim of investigating the benefit and applicability of the programme. A total of 128 new hearing aid candidates participated in three studies at the Sahlgrens hospital and at four other hearing centres in smaller Swedish towns. In a controlled study the AF group was more positive to their hearing aids and to the fitting period after 10 months. They used their hearing aids more frequently and felt psychologically more secure with them. It was established that the AF programme could well be applied in the clinical routine for a majority of new hearing aid patients. Old age per se was not found to be a relevant exclusion criterion. The positive outcome of the AF programme has stimulated the Swedish Institute of the Handicapped to print 'Try Your Hearing Aid' with a manual, and to introduce it to all hearing centres in Sweden. PMID- 2224294 TI - The international scene in biological and medical libraries. AB - This article introduces the Bulletin's special issue devoted to international health sciences librarianship with a discussion of the formal structures of international cooperation. The International Federation of Library Associations and Institutions' (IFLA) Biological and Medical Sciences Libraries Section conducts activities along four strands: world and regional health sciences library directories, mutually supportive regional groupings, a quarterly newsletter, and the quinquennial International Congress on Medical Librarianship. These activities, as well as those of other organizations, make up the formal international structure of health sciences librarianship. PMID- 2224295 TI - Bibliometric aspects of medical information in Arab countries. AB - This paper discusses the current state and development of health and biomedical literature in Arab countries. The study concentrates on the Arabic sources of medical articles, and surveys and analyzes the size of the literature and its development in the past 100 years. Two aspects of these sources are covered: the Arab medical information sources published within the Arab region, and those published outside the region. This includes the quantity of material available within and outside the Arab region. The size of the Arab medical literature indicates that it is worthy of collection. Treatment of the Arab medical literature, a pressing and urgent issue, is needed to assist in the research and development of an Arab medical infrastructure. PMID- 2224296 TI - Analysis of external and internal interlibrary loan requests: aid in collection management. AB - The analysis of 60,779 external interlibrary loan requests for copies of periodical articles from the collection of Erasmus University Medical Library in 1988 is described. The study was used for planning the length of backruns to be retained due to space limitations that forced the disposal of older volumes. More than 50% of requests were for the most recent two-year period, and 90% of requests could be filled with a twenty-year run of periodicals. In 1989, 4,157 internal requests were received for periodicals not owned; these were analyzed to determine those most commonly requested. Prior to subscribing, new titles were reviewed as to price, bibliometric indicators, number of requests, length of backfile, and the number of requesting departments. The Library Advisory Board decides on cancellation or purchase of periodicals; the elements considered are described. PMID- 2224297 TI - The need for a drug abuse documentation center in India. AB - The problems of alcoholism and drug addiction are major concerns in India. Alcohol and drugs were used in the past to obtain relief from pain and misery and to attain a state of forgetfulness. India is presently facing the problem of increased trafficking in drugs; heroin and hashish are supplied to the west through the subcontinent. Addiction has become a major problem in metropolitan centers. The Ministry of Welfare is responsible for drug abuse prevention programs and the rehabilitation of addicts. The Ministry of Health and Family Welfare is concerned with drug treatment. A deaddiction center, established at the All India Institute of Medical Sciences, became operational in 1988; it is responsible for health manpower training, research, and documentation. India has witnessed an exponential growth in the literature on drug abuse; it is no longer possible for a single library to acquire all of the international literature. There is a clear need to establish a drug abuse information center in India. This paper describes the aims, objectives, and planning for such a center and recommends the establishment of a national center in New Delhi with regional centers in other geographic areas. PMID- 2224298 TI - The use of grey literature in health sciences: a preliminary survey. AB - The paper describes some initiatives in the field of grey literature (GL) and the activities, from 1985, of the Italian Library Association Study Group. The major categories of GL are defined; a survey that evaluates the use of GL by end users in the health sciences is described. References in selected periodicals and databases have been analyzed for the years 1987-1988 to determine the number of articles citing GL, the number of GL citations found in selected periodicals, the various types of GL found, and the number of technical reports cited and their country of origin and intergovernmental issuing organization. Selected databases were also searched to determine the presence of GL during those same years. The paper presents the first results obtained. PMID- 2224299 TI - Regional health library service in northern Ireland. AB - The regional medical library service provided to physicians, hospitals, nurses, social workers, and health care administrators throughout Northern Ireland by the Queen's University of Belfast is described. A brief outline of the National Health Service in the United Kingdom is given, and the library service is described in terms of collections, cataloging, interlibrary loan, and reference. PMID- 2224300 TI - Health sciences libraries and information services in Bangladesh. AB - Basic problems relating to the status of health sciences libraries and information centers in Bangladesh are highlighted and discussed; strategies for improving the country's health sciences information services are suggested. A survey of libraries is reported, the country's national science and technology information policy is defined, and recommendations for action are proposed. PMID- 2224301 TI - National bias: a comparison of citation practices by health professionals. AB - It is hypothesized that health professionals in the United States and the United Kingdom are nationally biased in their citation practices. Articles published in the New England Journal of Medicine and Lancet were used to study citation practices of U.S. and U.K. authors. Percentages of cited references to material published in a specific country were calculated for both the New England Journal of Medicine and Lancet. Using a variation of a citation publication ratio based on Frame and Narin's original ratio, an attempt was made to quantify author bias. To calculate these ratios, values from SERLINE* and the British Library Lending Division were employed to find world journal counts. The results suggest that U.S. authors publishing in the New England Journal of Medicine and U.K. authors publishing in Lancet tend to cite material produced in their own countries more than would be warranted by the amount of material produced by these countries. In addition, these authors cited material produced in non-U.S. and non-U.K. countries far less than the amount of material produced by these countries would indicate. PMID- 2224302 TI - Information needs of academic medical scientists at Chulalongkorn University. AB - The information needs of scientists in English-speaking countries have been studied and reported in the library literature. However, few studies exist on the information-seeking patterns of scientists in developing countries, and no study has examined the information needs of medical scientists in developing Asian countries. This study investigated the information needs of academic medical scientists at Chulalongkorn University in Bangkok, Thailand. The results indicate that medical scientists have three types of information needs: identifying up-to date information, obtaining relevant studies and data, and developing research topics. Thai scientists' information-seeking behavior was different from that of scientists in developed countries. The study shows a high use of libraries as information providers; Thai medical scientists rely heavily on information from abroad. PMID- 2224303 TI - Options for the disposal of unwanted donations. AB - Donations of biomedical books and journals frequently duplicate the holdings of a receiving library. A decision must then be made concerning the distribution of the material to other libraries that may need it. What options are available to the librarian? Are many volumes of valuable material destroyed each year because libraries lack the necessary staff, space, or money to distribute donated materials? Are libraries restricted in choice of methods for distribution or unaware of available options? A survey questionnaire was mailed to 150 health sciences libraries in the spring of 1988 to determine the various methods used to dispose of unwanted gift materials. A total of 113 responses was received (75% return rate). This paper reports the results and discusses some of the creative methods used by receiving libraries to place unneeded materials. Statistical comparisons are included for the methods used by academic, hospital, and other types of health sciences libraries. PMID- 2224304 TI - An evaluation of CD-ROM MEDLINE use in Thailand. AB - An analysis of requests for CD-ROM MEDLINE* searches from June to December 1987 at the Medical Library, Chulalongkorn University, was performed. Requests were received from eighty-two places, in Bangkok and the provinces; 97.8% were from government organizations. MEDLINE on CD-ROM was available from 1982 to date. Most users requested searches covering the previous five or six years. Users were surveyed regarding the service: just over 87% found the service user-friendly. In addition, users suggested that the library conduct search training programs, and more than half of the users noted that a single work station could not meet the search load. PMID- 2224305 TI - Research activities among health sciences librarians: a survey. PMID- 2224306 TI - MLA's international program. PMID- 2224307 TI - Project HOPE archive. PMID- 2224308 TI - The world of health sciences libraries. PMID- 2224310 TI - The information explosion. PMID- 2224309 TI - Government documents. PMID- 2224311 TI - To amputate or not? Information needed PDQ! PMID- 2224312 TI - BIOSIS previews. PMID- 2224313 TI - Influencing our future. PMID- 2224314 TI - [The various uses of in-vitro reconstituted skin]. AB - Skin is one of the most suitable organ to assess reconstruction in vitro. After forming dermis, by incubation of fibroblasts within a network of collagen fibers, a layer of cultured keratinocytes reconstruct the epidermis. This tissue, even though imperfect, represents a valuable tool for the study of cell physiology, the demonstration of interaction between cell and their support and exchange of information between cells of different types. Within the model, cells acquire a state of differentiation close to that observed in vivo. Reconstructed skin may be used for the study of physiopathology of various cutaneous diseases and allows pharmacotoxicological studies. Keratinocytes in culture, as well as the reconstructed skin, have been successfully used for grafting cutaneous defects. PMID- 2224315 TI - [The latissimus dorsi territory: a privileged donor site]. AB - The latissimus dorsi is one of the most used donor areas in various fields of reconstructive surgery. After a short historical review, the main anatomical features, classical as well as new, are outlined in the view of reconstructive procedures. If it now demonstrated that the exceptional reliability of this myocutaneous territory allows to perform operations that belong to the routine like taking part in mammary reconstructions or to more sophisticated techniques, like in head and neck reconstruction. Among future prospects, we will consider the total mammary reconstruction and the cardiomyoplasty. PMID- 2224316 TI - The changing agenda for health care in America: balancing need and commitment. Annual Health Conference, May 9-10, 1989. PMID- 2224317 TI - New initiatives for children's services. PMID- 2224318 TI - New entitlement programs. PMID- 2224319 TI - The nation's health goals: social change, problems and opportunities. PMID- 2224320 TI - The nation's health goals. The new political dynamics: federal and state initiatives. PMID- 2224321 TI - Policy implications of socioeconomics. PMID- 2224322 TI - Physician payment and the resource based relative value scale. PMID- 2224323 TI - Dilemmas in payment, reimbursement and regulation. Achieving a balanced perspective on state regulation. PMID- 2224324 TI - A hospital administrator's perspective on regulation. PMID- 2224325 TI - Dilemmas in payment, reimbursement, and regulation. A practicing physician's experience. PMID- 2224327 TI - Treatment of the asthmatic child. AB - At the end of 1983 the outpatient clinic at the National Children's Hospital in San Jose, Costa Rica, adopted a new program for treating children with asthmatic crises. Use of adrenaline was discontinued, and administration of salbutamol in aerosol and short courses of corticosteroids was introduced; also, a special outpatient room was set aside for treating pediatric asthma cases. Between 1984 and 1986 this program's marked superiority was demonstrated by many developments- including reduction of both initial hospitalizations and readmissions for pediatric asthma by nearly 70%. PMID- 2224326 TI - Physicians and managed care programs. PMID- 2224328 TI - Health and tourism in the Caribbean. AB - Health and tourism impact on each other in the Caribbean, so it is both appropriate and necessary that those concerned with tourism in the region should consider health issues. The health and environment of the Caribbean can have good or bad effects upon the health of visitors, and tourism has health consequences for local residents. Tourism for health purposes also needs to be considered. This article points out the major issues related to these interactions, indicates where more data are needed, and suggests lines of future action. PMID- 2224329 TI - Prevalence of Wuchereria bancrofti in Georgetown, Guyana. AB - A random sample bloodsmear survey was conducted during evening hours in Georgetown, Guyana, to determine the prevalence of Wuchereria bancrofti microfilariae. In all, 182 of 2,818 persons tested (6.5%) yielded positive results--indicating that the overall prevalence of Bancroftian filariasis has not diminished and may be on the rise. Relatively high prevalences found in children and adolescents point to active transmission. It appears likely that certain socioeconomic and environmental factors have been contributing to such transmission, and that similar factors could encourage increased transmission elsewhere in the Americas as well. PMID- 2224330 TI - Field evaluation of Bacillus thuringiensis var. israelensis for control of black flies in the North Littoral Zone of Brazil's Sao Paulo State. AB - The impact of three flowable concentrate formulations of Bacillus thuringiensis var. israelensis (H-14) upon Simulium pertinax larvae was evaluated in 24 coastal streams of Brazil's Sao Paulo State. While no significant differences were found regarding the three formulations' effectiveness, significant correlations were found between the discharge rates of individual streams and the distances over which at least two of the formulations were carried effectively downstream to produce 80% mortality. The relatively short carry distances found for small streams could pose difficulties for control programs that need to treat large numbers of such streams, and suggests a need for research directed at increasing the distances B. thuringiensis (H-14) formulations can be carried. PMID- 2224331 TI - The elderly in Barbados: problems and policies. AB - Empirical data on conditions affecting elderly people in the Caribbean are very limited. To help deal with this lack of information in the specific case of Barbados, in 1982 a survey was conducted of 525 randomly selected people 65 years of age or older. This article summarizes data derived from that survey in order to provide an overview of the social and economic circumstances affecting Barbados' elderly population. While it is true that these circumstances do not necessarily mirror those found elsewhere, they clearly have elements in common; and it seems likely that the survey approach applied in this instance could prove useful elsewhere in obtaining worthwhile information. PMID- 2224332 TI - Aging: a challenge beyond the year 2000. PMID- 2224334 TI - The role of social security in the provision of medical care in the English speaking Caribbean. PMID- 2224333 TI - Combating AIDS in the Caribbean: a coordinated subregional approach. PMID- 2224335 TI - Prevention and control of hospital infections in Latin America and the Caribbean. PMID- 2224336 TI - Safe current limits. PMID- 2224337 TI - Technology management in the health care environment--yesterday, today, and tomorrow: Part 1. PMID- 2224338 TI - Designing and implementing a computerized parts-inventory management system. PMID- 2224339 TI - Surviving and growing in the '90s: managerial methods for the hospital-based BME/CE department. PMID- 2224340 TI - The design of a microcomputer-controlled voice onset time analyzer. AB - In spoken syllables such as "ta," the interval between the release of the tongue constriction for the stop consonant /t/ and the onset of the vowel is called voice onset time, or VOT. Voice onset time is an important determinant of whether the initial consonant will be heard as a /t/(values of 60-90 ms) or as a /d/ (values of 0-30 ms). VOT information, immediately following a spoken syllable, can provide a speaker with feedback for modifying speech production. Such information can help the hearing-impaired learn to speak. It may also help people who learn English as a second language, since they often produce /b,d,g/ and /p,t,k/ with inappropriate VOT values. A prototype portable device measures VOT for initial voiced and voiceless stop consonants (e.g., "da" and "ta"). A dual microphone method is used for acoustic measurement. A microphone in front of the mouth picks up the radiated acoustic signal; another over the larynx transduces vocal vibrations that mark the beginning of a vowel. Analog circuits process the transducer signals and provide gain and filtering. Filters were designed on the basis of the acoustic properties of stop consonants. The output from each analog circuit is fed to a comparator that compares the signal level with a fixed threshold voltage reference. A digital timer starts when the amplitude of the oral signal voltage exceeds a threshold and stops when the laryngeal signal voltage exceeds a threshold. VOT values obtained by the device were compared with those made from digital waveforms of words spoken by five talkers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224341 TI - A pressure-sensitive mat for measuring contact pressure distributions of patients lying on hospital beds. AB - The authors describe a novel system for sensing and displaying the distribution of contact pressure caused by a patient's lying on a hospital bed. The system includes a flexible, pressure-sensitive mat, electronics to activate the mat, a small computer to process data, and a color video display. The present prototypes can sense pressure at 1,536 discrete locations in a rectangular grid of 24 x 64 nodes, each node representing an area of 4 cm2. The computer receives data from each node and displays the results as a false-color map, refreshable every 5 seconds. The pressure-sensitive mat itself includes two orthogonal arrays of ribbon-like conductors, composed of silver-coated nylon fabric, which are separated by insulating open-cell foam rubber. The system monitors the electrical capacitance between selected pairs of horizontal and vertical conductors on opposite sides of the foam. The crossing points form pressure-sensitive nodes. Increased contact pressure compresses the foam, thereby decreasing the distance between the conductors and increasing the capacitance. Node capacitance is determined by measuring the current through it from a voltage source. The outputs of the various nodes are scanned, normalized, and converted to pressures using the known compressive stress-strain relationship for the foam, and the data are then displayed as a false-color image of the pressure distribution. PMID- 2224342 TI - The accuracy of rapid oscillometric blood pressure determination. AB - The Dinamap 1846SX (DIN) offers a "stat mode" (SM) for rapid repetitive blood pressure determinations, but its accuracy has not been reported. Thirty patients who required an intra-arterial catheter (IAC) for management of anesthesia underwent induction with concomitant noninvasive blood pressure measurement provided by a DIN set in SM. Computerized automated data acquisition recorded digital outputs from both monitors at the time of new SM readings. Systolic pressure mean absolute error (MAE) was 13.3 +/- 5.7 mmHg (mean +/- SEM) and the mean error (bias) was -8.7 +/- 9.8 mmHg. Mean pressure MAE was 6.8 +/- 3.4 mmHg and bias was -0.5 +/- 6.3 mmHg. Diastolic pressure MAE was 7.0 +/- 3.3 mmHg and bias was -0.3 +/- 6.5 mmHg. There was a tendency for systolic pressure readings to underestimate IAC pressures at higher pressures. These findings echo results reported previously for DIN operating in its normal mode. Rapid arterial pressure determination by SM does not appear to compromise accuracy. PMID- 2224343 TI - Organizing a study program for BMETs. PMID- 2224344 TI - The venous drainage of nerves; anatomical study and clinical implications. AB - The venous drainage of the peripheral nerves was studied in the upper and lower limbs of two human fresh cadaver subjects after total body perfusion with a radio opaque lead oxide mixture. Four patterns of extraneural drainage were identified in which the venae nervosa drained: directly to the venae comitantes of the neurovascular bundle; indirectly via nearby veins, derived usually from muscles; to the periarterial venous plexus; or, in the case of the cutaneous nerves, to the perivenous plexus. The various patterns of the drainage along the length of the radial, median, ulnar, sciatic, anterior and posterior tibial nerves were identified. A rich longitudinal plexus of veins exists on and within the nerve which appears to be mainly free of valves. The large venae nervosa usually contained valves, whereas the tiny veins draining the nerves were valveless or exhibited a sentinel valve at their entry point into a larger venous channel. The clinical implications of these results are discussed in relation to the mobilisation of nerves, the use of island nerve flaps, possible donor sites for free arteriolised neurovenous flaps and the compressive nerve syndromes. PMID- 2224346 TI - Titanium in reconstructive surgery of the skull and face. AB - Titanium is widely used as an implant material. This report describes its use for cranioplasty and malar defects and the technique used to fashion these prostheses in a centre which does not have the facility for producing computer-generated full-size craniofacial models. The use of these prostheses has produced very satisfactory results with minimal morbidity and no complications. PMID- 2224345 TI - Epidermoid cyst and cholesterol granuloma of the orbit. AB - Epidermoid cyst and cholesterol granuloma have been confused, but these are different lesions. A case of recurrent orbital epidermoid cyst and another case of orbital cholesterol granuloma are presented in order to describe their distinct pathological, clinical and imaging characteristics and their surgical management. Advanced investigation using our custom-designed three-dimensional imaging allowed a better appreciation of the exact location, and optimal planning of the surgical treatment. The same surgical approach was used for both lesions: total resection via a coronal incision and immediate reconstruction of residual defects using skull bone grafts. PMID- 2224347 TI - Three anteromedial fasciocutaneous leg island flaps for covering defects of the lower two-thirds of the leg. AB - Three different fasciocutaneous island flaps based on the medial septocutaneous vessels of the leg have been successfully transferred in eight patients. The flaps are based on three segments of the anteromedial aspect of the leg where their feeding vessels were most frequently identified. These anteromedial fasciocutaneous leg island flaps are thin, reliable and safe. They are relatively easy to elevate and are useful for covering defects of the lower two-thirds of the leg. PMID- 2224348 TI - Distally-based random fasciocutaneous flaps for multi-staged reconstruction of defects in the lower third of the leg, ankle and heel. AB - Distally-based random pattern fasciocutaneous flaps were used to reconstruct defects of the lower third of the leg, the ankle and the heel in eight patients. Though a multi-staged procedure, this simplified fasciocutaneous flap design ensured safe transfer of tissue to defects in which it would otherwise have been very difficult to have obtained cover. This paper discusses the anatomical basis of the distally-based random pattern fasciocutaneous flaps and reviews the design, surgical technique, advantages, limitations and complications of these flaps. PMID- 2224349 TI - Lateral sural cutaneous artery island flap in the treatment of soft tissue defects at the knee. AB - This paper describes a flap for covering defects around the knee. Dissections of 20 legs showed that in the majority the lateral sural cutaneous artery branched from the popliteal artery and descended along the posterolateral aspect of the leg together with two venae comitantes and the lateral sural cutaneous nerve. An island flap was designed, pedicled on these vessels and nerve, and was used in 17 patients with defects around the knee, including acute trauma (three cases), soft tissue tumours (three cases), unstable scar or ulcer (seven cases), and chronic osteomyelitis or infected open fractures with tissue loss (four cases). All the flaps survived entirely and possessed normal sensation. Furthermore, it was not necessary to sacrifice the main vessels of the lower leg. PMID- 2224350 TI - A comparative study of surgical results with rotation-advancement and triangular flap techniques in unilateral cleft lip. AB - This paper presents a randomised comparative study of surgical results of unilateral cleft lip repair with 58 rotation-advancement and 50 triangular flap repairs, the two commonly used types of repair at present, carried out over a period of 6 years. The surgical results following both repairs were assessed on a scoring basis. No significant difference was found in overall postoperative appearance of lip and nose between the two types of repair. As a result, we recommend either technique for unilateral cleft of the lip. PMID- 2224351 TI - Open reverse-U incision technique for secondary correction of unilateral cleft lip nose deformity. AB - A new technique for secondary correction of unilateral cleft lip nose deformity is described. It is a combination of Tajima's reverse-U incision and Rethi's columella-alar rim incision techniques. It gives a markedly increased exposure under better direct vision and enables easier and more accurate handling of the nasal framework in secondary correction of the unilateral cleft lip nose deformity. PMID- 2224352 TI - The redistribution of collagen in expanded pig skin. AB - Silicone tissue expanders were inserted subcutaneously in the buttocks of nine young pigs and gradually inflated to maximum capacity over 5 weeks. On the control side the expanders were left uninflated. Island buttock flaps were then raised, the expanders removed and the flaps spread into the same sites for 10 days. The tissue was harvested. Area measurements and full thickness skin biopsies were taken 10 days after flap inset in order to study the changes in collagen composition and isotypes in the skin layers. Ten days after inset of the flap the expanded skin had a mean 47% increase in surface area, was 9% thinner (from surface to implant), mostly due to thinning of the subcutaneous zone, but was not significantly different in water content, relative to the control skin. The expanded skin had a significant 9.3% increase (p less than 0.01, t test) in collagen content of the dermis. The relative proportions of Types I and III were not significantly changed by skin expansion in either the dermal/epidermal or subcutaneous/capsular zones. It is speculated that tensile factors during expansion stimulate the biosynthetic activity and/or mitotic activity of fibroblasts in the dermis to produce this gain in collagen in the expanded compared with unexpanded tissue. PMID- 2224353 TI - Foetal wound healing in a large animal model: the deposition of collagen is confirmed. AB - Foetal wound healing occurs without scarring. A scar is a collagen-rich repair tissue, and the absence of scarring in the foetus has raised questions concerning the presence and nature of collagen deposition in foetal wounds. Studies of collagen deposition in foetal wounds in small animals, performed late in gestation, have been equivocal. In this study, using a large animal with a long gestational period, the sheep, the deposition of collagen is confirmed. PMID- 2224354 TI - Lymph node transfer for the treatment of obstructive lymphoedema in the canine model. AB - The efficacy of transferring vascularised lymph nodes into lymphoedematous limbs was investigated. Stable below-knee lymphoedema was established in one hind limb of 10 dogs. The superficial inguinal lymph node and perinodal tissue from the normal hind limb was moved to the popliteal region of the lymphoedematous leg as a free vascularised transfer. In five dogs lymphaticolymphatic anastomoses between lymphatics of the node and proximal recipient site lymphatics were also performed. Circumferential measurements of the foot, ankle and midleg were obtained preoperatively and postoperatively at 3 and 6 months. These measurements showed postoperative reduction of the lymphoedematous legs compared to controls, with no added benefit from lymphaticolymphatic anastomoses. Technetium 99 scans and lymphangiography demonstrated re-establishment of lymphatic continuity in all recipient legs at 3 and 6 months post-transfer. Histological examination at 3 and 6 months revealed normal architecture in 9 of 10 nodes, although areas of lymphocyte depletion were common. Vascularised lymph node transfer to a lymphoedematous leg re-established lymphatic continuity and resulted in partial reduction of limb size. The addition of lymphaticolymphatic anastomosis to vascularized node transfer is neither necessary nor beneficial. PMID- 2224355 TI - Can chlorpromazine prevent flap necrosis? AB - The influence of chlorpromazine hydrochloride on failing, cranially-based dorsal flaps of female rats (Uje:WIST) was studied. The drug was injected subcutaneously into the abdomen pre- and postoperatively. The dosage was 1.5 mg/100 g preoperatively and 0.75 mg/100 g body weight every 12 hours following flap replantation for 10 consecutive days. No improvement in the survival rate was achieved by administration of chlorpromazine hydrochloride in this rat strain. PMID- 2224356 TI - A prospective trial of adrenaline infiltration for controlling bleeding during surgery for gynaecomastia. AB - Twenty patients with gynaecomastia undergoing operations on 33 breasts were entered into a prospective randomised controlled clinical study. The breasts were randomised to receive nothing or adrenaline infiltration prior to mastectomy. Blood loss during surgery and drainage afterwards were compared between the two groups. Statistical analysis using the Wilcoxon rank sum test (two-tailed) showed a statistically significant reduction in operative blood loss (p less than 0.01) but no difference in postoperative drainage. There was no adverse effect on the viability of the skin flaps or the nipple-areola complex. PMID- 2224357 TI - A radical approach in the treatment of the deviated nose. AB - Surgical attempts to straighten a deviated nose do not always produce a satisfactory result, partly due to the surgeon's inability to straighten the anterior part of the nasal septum or to maintain it in a correct position postoperatively. In a radical departure from accepted norms we have, in eight cases, excised the deviated part of the anterior nasal septum and replaced it with a bone graft. The background and the need for this procedure are explained, followed by a case report in some detail. Details of the eight cases are given in a table and representative cases are presented with illustrations and comments regarding the problems encountered with the present method. PMID- 2224358 TI - Immediate exposed skin grafting in children's burns. AB - The technique of immediate exposed skin grafting following early tangential excision of burns in children overcomes the difficulties of applying dressings with the attendant risk of graft loss from shearing forces. We report on 36 patients treated by this method. Wound healing was achieved in all patients without the need for further surgery. PMID- 2224359 TI - Malignant melanoma of the external ear. AB - Twelve patients with primary melanoma of the external ear were treated during a 10-year period. Ten patients were males. Median melanoma depth was 2.1 mm and seven patients had lesions deeper than 2 mm. Eight of 12 lesions were either Clark level IV or V. Six patients had wedge excisions of the primary lesion and all developed recurrent disease (local: three). Six patients underwent wide excision and none developed local recurrence. All patients with primary disease less than 2 mm are alive. Only two of seven patients with lesions deeper than 2 mm have survived. The definitive excision for melanoma of the ear should encompass wide margins despite the cosmetic consequences. Lesser procedures inevitably lead to local recurrence. Melanoma deeper than 2 mm penetration on the ear in our series had a poor prognosis. PMID- 2224360 TI - Buccal mucosal flaps in nasal reconstruction. AB - Buccal mucosal flaps provide a simple and effective method of replacing nasal mucosal lining. This technique has been used in 15 patients requiring reconstruction of full thickness defects of the lateral nasal wall and tip of nose, in combination with a variety of local flaps for skin cover. The buccal mucosal flap is of particular value in reconstructing the common defect of the lower lateral nasal wall and alar rim where more bulky reconstructions often distort the airway. PMID- 2224361 TI - Successful replantation of nose by microsurgical technique, and review of literature. AB - We present a case of total amputation of a major portion of the nose of a 10-year old boy, which was successfully replanted by microsurgical technique. A 489-year review of the literature revealed the rarity of successful nasal replacement following amputation. PMID- 2224363 TI - Vascularised reconstruction of the clavicle. AB - A rare malignant tumour presented as a pathological fracture in the clavicle of an 11-year-old girl. This was resected and the defect reconstructed using a pedicled bilobed flap based on the thoracodorsal system with latissimus dorsi and serratus anterior with a rib to replace the clavicle. The innervation of both donor muscles was preserved. The reconstruction was cosmetically acceptable and maintained the function of the thoracohumeral articulation. Although the use of vascularised rib grafts in composite flaps is well documented, this is the first report of clavicular reconstruction using the technique. PMID- 2224362 TI - Immediate reconstruction of the penis with an iliac flap. AB - Immediate reconstruction of the penis can save time and significantly reduce postoperative psychological morbidity. A patient suffered a cancerous lesion in his glans penis. After total amputation, an iliac flap based on the superficial circumflex iliac artery was used to reconstruct the penis. The subcutaneous tissue around the vascular pedicle was carefully preserved for enhancing the venous drainage of the new penis. A self-sculptured silicone implant was inserted later to increase the penile rigidity. The advantages of this technique include ready availability, easy mobilisation, hairlessness, elimination of multi-staged procedures, and saving time. The patient is pleased with the operative results. PMID- 2224364 TI - A simple penile dressing following hypospadias surgery. AB - A single layer of surgical gauze applied with adhesive provides a simple and inexpensive dressing for use following hypospadias repair. It splints the penis to the abdomen, supports the wound and secures the catheter while permitting observation and wound care. PMID- 2224365 TI - A chair for patients with burns of the back. PMID- 2224366 TI - Confusion of the use of the term "septocutaneous". PMID- 2224367 TI - Educating the psychiatrist of the 21st century. AB - Psychiatry is under threat from developments within mental health care. In educating future psychiatrists, more emphasis should be placed upon: collaborative research; integrated teamwork, without interprofessional rivalry; work in primary care; the non-scientific components of psychiatry, centred upon relationships with patients; less dogmatic attitudes for or against psychoanalysis: psychiatry as a branch of medicine; and modern management and audit methods. Younger psychiatrists should be encouraged to take responsibility for shaping the future of the profession. PMID- 2224368 TI - Further investigation of the predictors of outcome following first schizophrenic episodes. AB - The outcome at two years of patients who were eligible for a study of first schizophrenic episodes was assessed in terms of occupation (n = 237) and in terms of number of days spent as an in-patient from the time of first admission (n = 252), and was related to social, behavioural, mental state and neurological measures during the initial admission. Poor outcome was in general associated with more social withdrawal, inactivity and abnormal social presentation and with more 'neurological soft signs'. Good occupational outcome in patients with a relatively short pre-treatment duration of illness was associated with the prescription of placebo medication during the follow-up period. PMID- 2224369 TI - Alcoholism: a follow-up study of participants in an alcohol treatment programme. AB - One hundred and twelve alcoholic patients treated by an intensive one-month residential programme were followed up for one year. As a group, they were socially disadvantaged and highly dependent on alcohol. Outcome of treatment was assessed at six months and one year following discharge by multiple measures which included assessments of drinking behaviour, measurements of social stability, neuroticism and self-esteem, and self-ratings of satisfaction with important aspects of day-to-day living. During the first six months following treatment, 37% were abstinent or drinking in controlled fashion; during the second six months, 53% achieved this status. Improvement in drinking status was positively related to improvements in all other outcome variables. PMID- 2224370 TI - 3H-imipramine binding to previously frozen platelet membranes from depressed patients, before and after treatment. AB - 3H-imipramine binding in 39 drug-free patients with major depression and 44 healthy controls did not differ significantly between the two groups, in male or female subjects or in subgroups of depressed patients divided by endogenicity or dexamethasone suppression test result. 3H-imipramine binding in depressed patients drug-free for less than three weeks did not differ from those drug-free for longer intervals or from controls. A significant seasonal variation of 3H imipramine Bmax was found, with lower values in summer and autumn. Treatment of depressed patients with imipramine or lofepramine for six weeks increased KD and Bmax. Methodological modification (in preparation and storage of platelets) does not explain the major differences in results between this study (using frozen platelets), a previous one (using freshly prepared platelets) and others in general, although it might contribute to the range of values reported. PMID- 2224371 TI - Multimodal imaging in Alzheimer's disease. The relationship between MRI, SPECT, cognitive and pathological changes. AB - Patients with a clinical diagnosis of Alzheimer's disease were studied using MRI, SPECT, and psychometric tests. Significant correlations between focal perfusion deficits and focal cognitive deficits were found. Significant correlations between regional relaxation time of white matter and psychometric tests of diffuse and focal categories were also found. Pathological examination confirmed Alzheimer's disease as the only diagnosis. PMID- 2224372 TI - Daughters of people with dementia. Expressed emotion, strain and coping. AB - Twenty-five women who were the primary carers for a parent with dementia rated for expressed emotion (EE) and then divided into two groups: 11 with low-EE ratings and 14 with high-EE ratings. Although there were no differences between these groups in the levels of their parents' cognitive impairment, when such impairment was taken into account, high-EE subjects were found to report higher levels of strain and distress. More efficient coping strategies were reported by subjects who made fewer critical comments and more positive remarks. High-EE subjects more frequently had no living siblings, and were more likely to have had a respite break from caring. EE status was not associated with continuing care in the community at a nine-month follow-up. PMID- 2224373 TI - Further change in the pattern of mental illness in the elderly. AB - The methods of Roth's 1948-49 Graylingwell study, previously applied to a Crichton cohort of elderly patients of the years 1974-76, were repeated in 1984 86. The results support the continuing validity of Roth's classification of mental illness in the elderly, but changes in the diagnostic distribution of the cohort, previously observed in the 1970s study, are further in evidence in the 1980s one. Admissions of dementia cases continued to increase both relatively and absolutely, while the trend of increasing survival in dementia also continued. PMID- 2224374 TI - A double-blind placebo-controlled study of buspirone in diazepam withdrawal in chronic benzodiazepine users. AB - A double-blind placebo-controlled trial of 23 chronic benzodiazepine users showed that overall, buspirone did not appear to be helpful in alleviating benzodiazepine withdrawal symptoms. Buspirone (5 mg t.d.s.) or placebo was administered for four weeks before, during and after diazepam withdrawal. Patients taking buspirone had a markedly higher dropout rate (seven out of 11) than those taking placebo (one out of 12). Mean daily diazepam dosage at entry was significantly higher in the buspirone group, but overall initial diazepam dosage was not related to outcome. Higher subjectively rated anxiety at the start of withdrawal was significantly related to higher dropout rate, irrespective of treatment, and was greater (although not significantly so) in the buspirone group. PMID- 2224375 TI - Accounting for delusional misidentifications. AB - Accounts of the major DMSs are given using theoretical models of the functional components underlying recognition of familiar people. Thus, Capgras' syndrome is suggested to involve impairment of processes that can support 'covert' recognition of familiar faces in prosopagnosia. It therefore forms a potential 'mirror image' of the impairments underlying prosopagnosia, and earlier attempts to link the two conditions directly are questioned. Fregoli syndrome and intermetamorphosis are explained as defects at different stages of an information processing chain. Not only are these accounts consistent with the association of different DMSs with different brain injuries, but they also offer both suggestions for new inquiries and predictions about possible preserved and impaired abilities. PMID- 2224376 TI - Factors related to self-reporting of the pre-menstrual syndrome. AB - Menstrual health questionnaires were completed by a self-selected sample of the readership of a woman's magazine (n = 5457). Sixty-one per cent of subjects described themselves as suffering from pre-menstrual syndrome (PMS) and this was largely corroborated by ratings of symptoms pre-menstrually, menstrually and post menstrually for the most recent cycle. Mood symptoms were more strongly implicated than physical ones. Self-report of PMS was found to be modestly associated with aspects of parity and oral contraceptive use, but strongly and positively related to the duration of 'natural' menstrual cycles (i.e. uninterrupted by pregnancy or steroidal contraception) and to psychosocial stress. There were interactions among psychosocial factors and between psychosocial load and duration of natural cycles. PMID- 2224377 TI - A controlled study of psychological and social change after surgical gender reassignment in selected male transsexuals. AB - Of two groups of 20 patients accepted for gender reassignment surgery, one was offered early operation and therefore had had surgery by follow-up two years later, while the second was still awaiting operation at two-year follow-up. Although the groups were similar initially, significant differences between them emerged at follow-up in terms of neuroticism and social and sexual activity, with benefits being enjoyed by the operated group. PMID- 2224378 TI - Clinical features of patients attending a gender-identity clinic. AB - Of 106 patients attending a gender-identity clinic, 73% satisfied DSM-III criteria for transsexualism. These DSM-III positives had a significantly younger age of onset and were less likely to experience sexual arousal with cross dressing than those who did not satisfy DSM-III criteria. They were also significantly more likely to fulfil a definition of 'core transsexualism'. 'Core transsexualism' may represent a subgroup within DSM-III criteria for transsexualism and its defining features in this study were an early age of onset, low sexual activity, lack of sexual arousal with cross-dressing and homosexual orientation. Of the whole sample, 23% were referred for gender reassignment surgery, of whom 100% were DSM-III positive and 60% were 'core transsexuals'. PMID- 2224379 TI - Is parental age related to the risk of Alzheimer's disease? AB - Advanced maternal and paternal age were investigated as putative risk factors for AD in 198 clinically diagnosed Alzheimer patients and in 198 randomly selected healthy controls. No significant differences in average age of fathers and of mothers at birth of the subject were observed. The risk of AD was not significantly different across categories of maternal and paternal age. The association with parental age was not different for sporadic and familial AD. These findings do not support the view of a maternal or paternal age effect on AD. PMID- 2224380 TI - Do-Do abuse. AB - Three cases of prolonged abuse of Do-Do tablets, an over-the-counter remedy for "coughs, wheezing and breathlessness", are reported. They have an amphetamine like action and were used as easily obtained amphetamine substitutes, in one case to relieve social anxiety. Withdrawal symptoms similar to those following cessation of amphetamines occurred in two cases. Do-Do tablets are CNS stimulants and their abuse may be accounted for by the fact that they perhaps affect amine neurotransmitters. PMID- 2224381 TI - A psychiatric study of deviant eating behaviour among mentally handicapped adults. AB - A study of deviant eating behaviour among mentally handicapped adults in community placements is reported. Those individuals with a psychiatric disorder showed more deviant eating behaviour. Depressed subjects, in particular, showed an excess of the amount eaten and time spent searching for food, as well as the tendency to eat all sweet food presented to them. Non-food pica was uncommon, even among the autistic subjects. PMID- 2224382 TI - Firesetting in an adolescent boy with Asperger's syndrome. AB - Firesetting in children and adolescents is commonly associated with other antisocial acts that comprise conduct disorders. Asperger's syndrome is a rare pervasive developmental disorder. In the case presented we argue that the firesetting arose from the disabilities inherent in Asperger's syndrome. This also indicates that antisocial acts may be symptoms in other psychiatric syndromes as well as a specific conduct disorder. PMID- 2224383 TI - The validation of the Edinburgh Post-natal Depression Scale on a community sample. AB - The Edinburgh Post-natal Depression Scale (EPDS) was validated on a community sample of 702 women at six weeks post-partum using Research Diagnostic Criteria for depression. The estimates of sensitivity, specificity and positive predictive value, being based on a large random sample, offer improved guidelines for the use of the EPDS by the primary care team. PMID- 2224384 TI - Folie a trois among two Soviet-Jewish immigrant families to Israel. AB - In two cases of folie a trois, affecting two Soviet-Jewish families who emigrated to Israel, both elderly parents in both cases shared the paranoid delusional beliefs of an only child. Severe trauma in the past and social maladjustment in the present may be among the precipitating factors for the development of the shared paranoid disorder. PMID- 2224385 TI - The 'new cross-cultural psychiatry'. PMID- 2224386 TI - Impact of participating in research. PMID- 2224387 TI - Psychiatric sequelae of listeriosis. PMID- 2224388 TI - Limitations of double-blind trials. PMID- 2224389 TI - ROC analysis. PMID- 2224390 TI - The Lomax affair. PMID- 2224391 TI - Brain transplants: myth or monster? PMID- 2224392 TI - First-rank symptoms. PMID- 2224393 TI - Comparing the effects of alcohol and intelligence on text recall and recognition. AB - Forty male subjects were divided into two groups on the basis of their scores on a computerized intelligence test administered in a preliminary session. They then participated in a text recall and recognition experiment in which they received alcohol (1.0 ml/kg body weight) in one session and no alcohol in another session (the order being counterbalanced). Subjects were required to read a short passage, immediately recall as much of it as possible and then select from sets of four sentences the ones that appeared in the original passage (recognition). Although two different passages were used, and subjects knew about the memory tasks in advance, there was nevertheless a significant practice effect: subjects recalled 10.6 per cent more propositions on the second occasion than on the first, but this could be at least partly explained by the fact that they spent 10.0 per cent longer reading the second passage. There was also a significant 7.8 per cent slowing of reading time due to alcohol. Practice did not interact with either intelligence or alcohol on any measure of performance. Alcohol impaired the performance of high intelligence test scorers more than low scorers. The effects of intelligence and alcohol on free recall were quantitatively similar: high intelligence test scorers recalled 8.7 more propositions than low scorers; with alcohol, subjects recalled 8.3 fewer propositions than without alcohol. However, the effects were qualitatively different. The effect of intelligence was primarily on the recall of lower level propositions, whereas alcohol impaired the recall of both higher and lower level propositions. Furthermore, while there was no effect of intelligence on recognition, alcohol impaired performance such that more incorrect sentences were erroneously recognized, particularly those which altered the meaning of the original sentence, rather than merely its surface structure. In terms of Kintsch & van Dijk's (1978) model of text processing, the results are interpreted as suggesting that, while both intelligence and alcohol affect the capacity of the short-term memory buffer, there is an additional impairment with alcohol in the ability to select between higher and lower level propositions prior to filling the buffer. PMID- 2224394 TI - The psychometric properties of the Bortner Type A Scale. AB - Recent evidence indicates that the relationship between Type A behaviour pattern (TABP) and coronary heart disease (CHD) is dependent upon the method of measuring TABP. This suggests that the psychometric properties of TABP measures should be carefully investigated. This article examines one widely used TABP measure, the Bortner Scale, using data from 1320 working adults divided into three random samples. The reliability of the Bortner Scale as an overall TABP index is unacceptably low. However, further analyses indicate that, rather than reflecting a single dimension, the Bortner Scale contains two independent dimensions, one reflecting speed and the other reflecting competitiveness. The speed dimension was negatively related to job satisfaction and, to a lesser extent, positively related to anxiety and somatic symptoms, whereas the competitiveness dimension was positively related to job satisfaction. Implications for the use of the Bortner Scale are discussed. PMID- 2224395 TI - Name recall performance across the adult life-span. AB - Everyday name-recall tests were administered to 1205 adults ranging in age from 18 to 90 years. They were asked to recall sets of four, six, or 14 names of individuals who introduced themselves on videotape. Immediate recall, acquisition, and delayed retention were examined. The results showed consistent age-related declines in name recall. Declines in performance were more evident on sets of 14 names rather than four or six names. Age deficits remained across several acquisition trials within the set of 14 names. The largest declines were evident for the old-old (over 70), although there were also significant performance differences, on some analyses, between the young and middle-aged groups. Changes in performance were less apparent during the middle-aged years (40-60 years). Name recall was related to individual differences factors, reaction time and paired-associate memory for names. The value of assessment and intervention with name recall was stressed. PMID- 2224397 TI - The effects of photic stimulation and private self-consciousness on the complexity of visual imagination imagery. AB - Three levels of photic stimulation (6, 10, 18 Hz) were employed to induce visual imagination imagery in 40 female undergraduates, half of whom had been selected because they had an habitual interest in their own internal states and half because they had no such interest (high and low on a Private Self-conscious (PSC) scale). It was predicted, and found, that more complex images would be reported (1) under the averaged 6 and 10 Hz condition than under the 18 Hz condition, (2) under the 6 than under the 10 Hz condition, and (3) under the high PSC than under the low PSC condition. An interaction effect was also obtained such that the complexity of visual imagination imagery was greatest for the high PSC group, compared with the low PSC group, under the 6 Hz condition and least under the 18 Hz condition. Additional analyses were undertaken on the types of colour, form and movement reported by the high and low PSC groups under combined conditions of photic stimulation. The results of the complexity scores were discussed in terms of West's (1962) 'perceptual release' theory and several suggestions were made for future research. PMID- 2224396 TI - Understanding face recognition with an interactive activation model. AB - In this paper we describe how the microstructure of the Bruce & Young (1986) functional model of face recognition may be explored and extended using an interactive activation implementation. A simulation of the recognition of familiarity of individuals is developed which accounts for a range of published findings on the effects of semantic priming, repetition priming and distinctiveness. Finally, we offer some speculative predictions made by the model, and point to an empirical programme of research which it suggests. PMID- 2224398 TI - Anti-RNP antibodies and their clinical significance. PMID- 2224399 TI - How assiduously should one investigate for occult malignancy in an elderly or middle-aged patient with dermatomyositis or polymyositis? PMID- 2224400 TI - Impaired iron uptake and transferrin binding by erythroblasts in the anaemia of rheumatoid arthritis. AB - Serum and bone marrow from 18 patients with rheumatoid arthritis (RA) and five healthy controls were studied in order to establish a possible role of impaired iron uptake and transferrin binding by erythroblasts in the pathophysiology of anaemia of chronic disease (ACD) in RA. Iron incorporation into erythroblasts was reduced in patients with ACD using a method based on incubation of erythroblasts with radiolabelled 59Fe-125I-transferrin. It correlated negatively with C reactive protein (CRP). In iron deficient RA patients it tended to be reduced as well. These patients had the same level of RA disease activity as in ACD. Transferrin binding by erythroblasts was significantly impaired in ACD compared to controls, although it tended to be reduced in all RA groups. These findings suggest that impaired iron uptake by erythroblasts, probably due to decreased transferrin binding to erythroblasts, might be a pathophysiological factor in ACD in RA. PMID- 2224401 TI - The sulphated glycosaminoglycan levels in synovial fluid aspirates in patients with acute and chronic joint disease. AB - Proteoglycan levels were measured in a series of synovial fluid samples from patients with acute and chronic joint diseases using a modified chemical dye binding method. Levels found in 50 miscellaneous inflammatory arthritis fluids (mean = 173.2 +/- 90.9 micrograms/ml) were higher than found in either 50 with rheumatoid arthritis (96.3 +/- 31.3 micrograms/ml) or 50 with osteoarthritis (83.8 +/- 27.3 micrograms/ml). For comparison, proteoglycan levels were measured in 15 cadaver synovial fluids (98.9 +/- 44.2 micrograms/ml) and 12 synovial fluids from patients with sports injury (163.7 +/- 79.4 micrograms/ml). Patients were recruited into a trial where synovial fluid was aspirated as often as possible over a 6-month period during which the patients were followed using a number of well proven clinical parameters. No correlation was found between the degree of joint destruction as measured by X-ray damage and the concentration or total amount of proteoglycan in the synovial fluid. In addition, there was no correlation between the level or total amount of proteoglycan and any clinical parameter of disease activity. PMID- 2224402 TI - Patients with arthritis and anti-U1-RNP antibodies: a 10-year follow-up. AB - Five hundred and forty patients attending a rheumatology ward were screened for antinuclear antibodies (ANA) by indirect immunofluorescence (IFL). Seventy had a significant titre of ANA. Twenty-three had U1-ribonucleoprotein antibodies (U1 RNP-ab). The clinical findings in U1-RNP-ab-positive patients were consistent with mixed connective tissue disease (MCTD). Disease was more serious in the U1 RNP-ab-positive patients in terms of polyarthritis severity as well as mortality due to rheumatic disease. Thus, in this arthritis patient population, U1-RNP-ab positivity predicted an aggressive disease characterized by an erosive arthritis. PMID- 2224403 TI - Diffuse idiopathic skeletal hyperostosis (DISH) of the shoulder: a cause of shoulder pain? AB - Shoulder pain is a common complaint and shoulder hyperostosis a frequent radiological condition. However, little is known about the association between the clinical and radiological findings. To evaluate the clinical relevance of shoulder hyperostosis we performed a controlled, blind study of 99 hospitalized probands with and without thoracospinal hyperostosis on lateral chest X-rays. The study included grading of the shoulder hyperostosis on the basis of three bilateral standard radiographs, assessing shoulder pain in a standardized way by an interviewer and recording extraskeletal causes of shoulder pain. The prevalence of shoulder hyperostosis was doubled in probands with thoracospinal hyperostosis compared to controls (chi 2 = 5.90, P less than 0.025, n = 99). Shoulder hyperostosis, irrespective of thoracospinal hyperostosis, predisposed to shoulder pain (40% versus 18%, chi 2 = 4.06, P less than 0.05, n = 74). Shoulder hyperostosis in combination with thoracospinal hyperostosis (shoulder DISH) predisposed to shoulder pain to an even greater extent (46% versus 12%, chi 2 = 6.64, P less than 0.01, n = 47). We conclude that shoulder hyperostosis is a radiological finding of potential clinical relevance. PMID- 2224404 TI - The inhibition of NK cell function by azathioprine during the treatment of patients with rheumatoid arthritis. AB - Treatment with azathioprine of patients with rheumatoid arthritis leads to a dramatic reduction in the 4 h NK cytotoxicity against K562 cells. The 24 h cytotoxicity against K562 and U937 cells, however, remains intact. The generation of cell-free supernatant cytotoxic factor(s) after incubating non-adherent mononuclear cells with U937 cells for 24 h is similar in the azathioprine patients and the controls. A large part of this supernatant cytotoxicity is due to tumour necrosis factor alpha which can be inhibited by a specific monoclonal antibody. The mechanism of the reduced 4 h NK cytotoxicity remains unknown but is probably not related to the anti-inflammatory properties of azathioprine. PMID- 2224405 TI - Effect of non-steroidal anti-inflammatory drugs on neutrophil chemotaxis--an in vitro and in vivo study. AB - We have studied the effects of the two non-steroidal anti-inflammatory drugs (NSAIDs), nabumetone and indomethacin, on neutrophil chemotaxis in vitro and in vivo. When used in therapeutic concentrations in vitro, neither agent had any effect on the chemotactic response of neutrophils isolated from healthy volunteers. This was true for the three chemotactic agents studied: FMLP, zymosan activated serum and purulent sputum. Nabumetone and indomethacin decreased neutrophil chemotaxis over a period of 2 weeks in 12 normal subjects in vivo. The average chemotactic response to 10(-8) mol/l FMLP for all 12 during the control period was 42.1 +/- 6.1 cells per high power field and this fell to 26.1 +/- 4.9 (P less than 0.025) after 7 days and to 15.6 +/- 2.5 (P less than 0.005) after 14 days. The results were similar for both drugs analysed independently. The results suggest that NSAIDs have no effect on the chemotactic response of mature cells in vitro, but suppress chemotaxis progressively when given in vivo. This may be explained by an effect of NSAIDs on maturing cells prior to release into the circulation. PMID- 2224407 TI - Racial variation in serum creatine kinase unrelated to lean body mass. AB - In a group of 30 black and 30 white healthy workers, matched for age, sex and body weight, serum creatine kinase was significantly higher in black males than in white males (P less than 0.01). Seventeen blacks but only four whites had levels above the accepted upper limit of normal of 195 IU/l. There was no correlation with lean body mass. Elevation of serum creatine kinase need not signify disease in blacks, for whom a separate reference range should be established. Two cases are reported of physically healthy black men subjected to unnecessary investigation on the basis of persistently elevated serum creatine kinase. PMID- 2224406 TI - Does primary fibromyalgia exist? AB - Twenty-one of 25 consecutive primary fibromyalgia or fibrositis patients, identified during a 5-year period in a tertiary care day-ward for pain syndromes, were re-examined. Fifteen fulfilled criteria for fibromyalgia but unexpectedly, all cases had either psychiatric disturbance or thyroid dysfunction. Of the four patients not seen at follow-up, two had developed neurological diseases, another rheumatoid arthritis and one other hypothyroidism. Thus, after 5 years no patient fulfilled the criteria for primary fibromyalgia. Women occupied as manual workers were over-represented. Most patients reported beneficial effects of physiotherapy. None of the patients has been able to return to full time work. PMID- 2224409 TI - Patients' perceptions of staff in a department of rheumatology. AB - Three groups of 44 rheumatic patients were studied in a Regional Rheumatology Centre, and two out-patient clinics (one conducted by a consultant, the other by a nurse practitioner). A questionnaire determined their perceptions of staff members, their spouses, and the patients with whom they had most contact. In the usual in- and out-patient setting, patients preferred to be told about their condition by the consultant. In the clinic where they saw a nurse practitioner regularly, over half preferred to be told by her. The patients found it easier to discuss their condition with a nurse (particularly of a lower rank than a sister). Much came from spouses and other patients. The consultant and sister had important roles in reassuring the patients, but doctors were not successful in making patients feel useful and needed. Nurses were somewhat better--but not that good (30%). This was a vital role for the spouse, who nevertheless in hospital produced much anxiety, closely followed by visitors, other patients and doctors. Nurses and occupational therapists were very calming and relaxing people. PMID- 2224410 TI - Lesions of the mid-shaft of the humerus presenting as shoulder capsulitis. AB - We describe three patients who presented with pain and restriction of movement at the shoulder suggestive of capsulitis, but proved to have lesions of the mid shaft of the humerus. It is important to be aware of the possibility of this cause of a 'frozen shoulder', since radiographs of the shoulder are usually cropped at the mid-humerus and lesions at this level may easily be missed. A radiograph of the entire humerus, or an isotope bone scan, may be more useful than repeated shoulder radiographs in patients whose shoulder symptoms do not respond to standard treatment. PMID- 2224408 TI - Why is the supraspinatus tendon such a common site for calcification? PMID- 2224411 TI - Review of UK data on the rheumatic diseases--3. Osteoarthritis. PMID- 2224412 TI - Sacral osteitis after sonographically controlled follicular puncture for in vitro fertilization. PMID- 2224413 TI - Photochemotherapy for rheumatoid arthritis. PMID- 2224414 TI - Effects of D-penicillamine treatment on antioxidant enzymes in rheumatoid arthritis. PMID- 2224415 TI - Diagnosis of eosinophilic fasciitis. PMID- 2224416 TI - Age and calendar year of onset in sibling pairs with rheumatoid arthritis. PMID- 2224417 TI - Age and year of onset differences in siblings with rheumatoid arthritis. PMID- 2224418 TI - Primary care--the educational need. PMID- 2224419 TI - Free testosterone and depression in male rheumatoid arthritis (RA) PMID- 2224420 TI - Acute inflammatory polyarthritis following streptokinase. PMID- 2224421 TI - Effects of oral N-acetylcysteine on gold levels in rheumatoid arthritis. PMID- 2224422 TI - Vertebral involvement in tertiary syphilis. PMID- 2224423 TI - Behcet's syndrome and spondyloarthritis. PMID- 2224424 TI - Social facilitation effects in recognition memory. AB - This study investigates the effects of observer presence on recognition memory. The number of learning repetitions, the degree of association of category instance word pairs, and the time interval between acquisition and testing were manipulated. While the basic recognition data conformed well to previous findings in the learning and memory literature, predictions, derived from the drive theory of social facilitation found little support. Instead, study results seem best explained by descriptions of the cognitive processes employed by subjects both during the initial acquisition and later recognition of the category-instance pairs. PMID- 2224425 TI - The influence of permeability of group boundaries and stability of group status on strategies of individual mobility and social change. AB - According to social identity theory, striving of group members for enhancement of their social identity may be resolved through individual mobility (i.e. by dissociation from one's own group in order to gain membership of a higher status group), or by social change (i.e. by upgrading the status position of the in group as a whole). Individual mobility may only be achieved when group boundaries are permeable; social change is only feasible when group status is unstable. This study investigates how these structural characteristics of the intergroup situation affect group members' preference for the individual mobility or social change strategy. In a laboratory setting subjects were given bogus feedback to induce differential levels of individual ability and group status. Additionally, the permeability of group boundaries and the stability of group status were manipulated. The main results are that, generally, members of high status groups show more satisfaction and in-group identification than members of low status groups. Permeable group boundaries apparently induce a tendency to strive for individual mobility, regardless of the in-group's status position. In relation to members of impermeable groups, members of groups with permeable boundaries show decreased in-group identification; there is evidence of (anticipatory) identification with the higher status group instead. A collective attempt at social change seems to be evoked when group status is unstable. In all groups with unstable status, members indicate their readiness to try to improve their group's status position. Moreover, members of low status groups with unstable status positions show relatively strong in-group identification, despite the lack of positive distinctiveness available to the in-group at the time. PMID- 2224428 TI - Calcium oxalate crystallisation kinetics and the effects of calcium and gamma carboxyglutamic acid. AB - gamma-carboxyglutamic acid (GLA) is an amino acid with a high affinity for calcium. It is found in urine both as the free amino acid and incorporated into proteins such as osteocalcin. Free and bound GLA have been reported to be found at higher concentrations in the urine of stone formers than controls. We have investigated the effect of GLA and calcium, at physiological levels, on the crystallisation of calcium oxalate using a mixed suspension mixed product removal continuous crystalliser. GLA caused very significant changes in the crystallisation kinetics, but the effect was dependent on the calcium concentration. At 4 mM calcium, GLA decreased the growth rate and increased the nucleation rate; at 12 mM the reverse occurred. At all concentrations of calcium tested, GLA caused a significantly increased crystal mass to be produced. Our evidence supports the hypothesis that GLA modifies calcium oxalate crystallisation and could be a promoter of stone formation in vivo, particularly at moderately elevated levels of calcium excretion. PMID- 2224426 TI - The clam cystoplasty. PMID- 2224427 TI - Sedoanalgesia in urology: a safe, cost-effective alternative to general anaesthesia. A review of 1020 cases. AB - Sedoanalgesia is a technique developed to provide safe and satisfactory operating conditions for a wide range of patients independent of age and overall level of fitness (although its use in children remains to be established). It is suitable for both endoscopic and open procedures, day-cases and in-patients. When used in day-case surgery it significantly improves overall efficiency. It is recognised that day-case surgery is an important and cost-effective element in surgical care. With increasing restraints being imposed upon hospital finances, patient beds and staffing levels, any strategies designed to improve efficiency in this sphere of surgical activity are to be welcomed. That 93% of patients prefer sedoanalgesia to conventional general anaesthesia attests to its high degree of acceptability. The technique of sedoanalgesia, its applications and potential impact for urology are detailed. PMID- 2224429 TI - Chronic dehydration stone disease. AB - A study was made of 819 patients attending a metabolic stone clinic. A firm diagnosis was made in 708 (86%) and in 132 of these (19%) the diagnosis was thought to be chronic dehydration. The records were available for study for 87 males and 11 females in the chronic dehydration group. The mean age at presentation was 43 years. The causes of chronic dehydration were hot climate (62%), with hot occupation and low water intake almost equal in second place. In patients with a single cause of chronic dehydration, 57% also had a dietary risk factor for urolithiasis and this was most commonly high oxalate intake. Following dietary advice, the mean urinary volume increased from 1720 to 2475 ml/24 h. This was accompanied by a rise in mean urinary calcium from 6.02 to 6.96 mmol/24 h, presumably due to the calcium in the additional water drunk. Urinary oxalate did not change significantly. The mean follow-up time was 4.85 years and the stone recurrence rate was low. It was concluded that chronic dehydration is a common cause of urolithiasis; this can be treated satisfactorily by increasing water intake plus dietary advice in certain cases. PMID- 2224430 TI - The use of internalised ureteric stents in renal transplant recipients. AB - Since 1982, we have used internal indwelling ureteric stents for the management and prevention of ureteric reconstruction complications in 28 renal allograft recipients. A total of 30 stents were placed in 18 patients either diagnostically or therapeutically in the management of allograft ureteric obstruction. In 16 patients internal stents were placed at the time of reconstruction for primary ureteropyelostomy (3), secondary ureteropyelostomy (8), repeat reimplant (3) and repair of ureteric or pelviureteric junction injury (2). Complications included 3 episodes of transplant pyelonephritis, proximal stent migration (1), persistent bacteriuria (1) and prolonged healing of a ureteropyelostomy (1). Internalised ureteric stenting is a safe and effective means of managing or preventing ureteric reconstruction complications in renal transplant recipients. PMID- 2224431 TI - Ureteric substitution with Boari bladder flap. AB - Between 1986 and 1989, 12 patients underwent ureteric substitution with a Boari bladder flap at this Institute. The indications were ureteric injury following hysterectomy, difficult forceps delivery, difficult ureterolithotomy, ureteric strictures caused by a Dormia basket and previous ureteric surgery, tuberculosis, retroperitoneal fibrosis and a post-ureteric reimplantation fistula. There were 2 patients with a solitary kidney and 2 in acute renal failure. Double J stenting was carried out in 11 patients and the stent was removed 3 to 6 weeks post operatively. Good results, with no morbidity or mortality, were achieved in all but 1 patient where a simple Silastic stent had migrated to the pelvis and required open surgery to remove it. We attribute our success to the tension-free anastomosis, a wide based posterior flap with preservation of its vascular supply, the use of a double J stent and vicryl suture material. PMID- 2224432 TI - Initial evaluation and response criteria for patients with superficial bladder cancer. Report of a workshop. PMID- 2224433 TI - Variations in urethral and bladder pressure during stress episodes in healthy women. AB - Pressure variations in the urethra and bladder during stress episodes and their time separations were investigated in 30 healthy female volunteers. The pressure was measured by means of a double microtip transducer catheter with the distal sensor in the bladder and the proximal sensor at the bladder neck, the mid urethra and the distal urethra. In advance of the pressure spike during cough a pressure rise was demonstrated in the bladder and at all 3 sites of measurement in the urethra. The urethral pressure increments preceding and following the pressure spike were statistically significantly higher in the mid-urethra than the corresponding bladder pressures. This active urethral pressure generation in the mid-urethra and distal urethra was initiated 200 ms before the bladder pressure began to rise. The pressure in the urethral high pressure zone was higher than the bladder pressure in all cases. Passive pressure transmission to the urethral high pressure zone can take place only insignificantly due to a continuous higher pressure inside the urethra than in the bladder and due to the location of the high pressure zone in the demarcation of the abdominal cavity. It was concluded that the urethral pressure rise in the high pressure zone during stress episodes is mainly generated actively by intra- and/or peri-urethral structures. PMID- 2224434 TI - Prostatic carcinoma: histological and immunohistological factors affecting prognosis. AB - Neuro-endocrine or paracrine cells of the human prostate and urethra have been identified by various methods, predominantly silver stains and immunocytochemistry. The incidence of neuro-endocrine differentiation in prostatic carcinoma has varied considerably from 10 to 100%, but has not been studied previously as an independent factor affecting prognosis. Nucleolar organiser regions (NORs) are loops of ribosomal RNA occurring in the nucleoli of cells which ultimately process RNA genes. NORs have been demonstrated by silver (Ag) staining techniques and have been studied in numerous malignant tumours. A pilot study from this laboratory has shown a distinct and significant difference in AgNOR staining between prostatic carcinoma and benign prostatic epithelial hyperplasia. A retrospective study was performed with at least 6 years' follow up. This confirmed the presence of neuro-endocrine cells in more than half of the patients under investigation. A significant correlation between survival and the absence of neuro-endocrine cells was demonstrated. AgNOR staining was shown to be of no prognostic value. PMID- 2224435 TI - Distribution of bony metastases in prostatic carcinoma. AB - Fifty-five prostate cancer and 55 breast cancer patients with positive bone scintigrams were studied. The pattern of spread in the axial skeleton and pelvis showed differences between the 2 groups. This difference was not related primarily to bone volume at the site of metastasis. The difference in distribution of bony metastases between breast and prostate is explained by our knowledge of Batson's vertebral venous plexus. PMID- 2224436 TI - Increased survival of patients with massive lymphadenopathy and prostate cancer: evidence of heterogeneous tumour behaviour. AB - The survival of patients with prostate cancer and radiologically detectable lymph node enlargement has been studied prospectively over an 8-year period. Computed tomography in 108 patients presenting with symptoms, signs or biochemical results suggesting lymphatic spread revealed pelvic or abdominal node masses in 60 patients; in 29 (48%), the masses measured more than 4 cm and the maximum node diameter was 15 cm. Two-thirds of patients had advanced (T3/T4) tumour stage. Following treatment, actuarial survival in all 60 patients with nodal enlargement was 40% at 5 years. Within this group, survival in 22 patients with lymphadenopathy but negative bone scans at diagnosis was significantly better than that of 38 patients with both node and bone disease (70% vs 20% at 5 years). This improvement was related both to an apparent inability of certain tumours initially to progress and seed within bone and to a marked sensitivity of the node masses to subsequent hormonal manipulation. Primary tumour grade was proportionally similar in both groups. Unexpectedly, 6 of the 38 patients with combined disease obtained a complete remission after treatment. The reason for this heterogeneous biological behaviour remains unclear; but these observations underscore the importance of vigorous treatment in all patients with advanced lymph node disease. PMID- 2224437 TI - Persistent carcinoma in situ of the testis after chemotherapy for advanced testicular germ cell tumours. AB - The chemosensitivity of testicular carcinoma in situ (CIS) was analysed in 25 testes excised 10 weeks to 4.5 years following platinum-based chemotherapy. CIS was present in 8 of the 23 evaluable cases (35%), in 5 of which the lesion coexisted with invasive germ cell tumour. It is concluded that CIS may persist or recur after chemotherapy. This has implications for occult presentation of metastatic germ cell tumours and also for the management of the contralateral testis in patients with testicular germ cell tumours. PMID- 2224438 TI - The importance of prognostic factors in the individual treatment of patients with disseminated germ cell tumours. AB - Following chemotherapy for disseminated testicular cancer, 55 patients underwent surgery because of residual tumour. The histological findings were viable tumour in 12 patients, mature teratoma in 12 and fibrosis and/or necrosis in 31. Retroperitoneal abdominal masses were evaluated radiographically before and after chemotherapy. The reduction in size of these masses after chemotherapy appeared to have prognostic significance. A decrease of more than 70% was always associated with fibrosis. A residual mass over 50 mm indicated viable tumour or mature teratoma. Seminoma or embryonal carcinoma was more likely to result in fibrosis/necrosis in the resected tissue. Both the Indiana and the EORTC classification models can be used for prognosis. Radiographic measurements before and after chemotherapy are of considerable prognostic significance. These objective indicators help in planning treatment and so diminish the side effects of therapy and maintain or even increase the high cure rate in disseminated testicular cancer. PMID- 2224439 TI - Vesicocutaneous fistula secondary to bladder instability. PMID- 2224440 TI - Thirteen-year survival of patient with recurrent metastatic renal carcinoma. PMID- 2224441 TI - Granulomatous hepatitis following intravesical BCG therapy. PMID- 2224442 TI - Testicular haematoma: a delayed complication of testicular vein ligation. PMID- 2224443 TI - A giant renal stone. PMID- 2224444 TI - Primary amyloidosis of the bladder. PMID- 2224445 TI - Complete prolapse of the urinary bladder. PMID- 2224446 TI - Pelvic irradiation, the ureter and extracorporeal shockwave lithotripsy. PMID- 2224447 TI - Minimisation of stone deflection during extracorporeal shockwave lithotripsy monotherapy for ureteric calculi in situ. PMID- 2224448 TI - Confirmation of position of double J stent inserted at open operation. PMID- 2224449 TI - Multiple transverse taeniamyotomy of the caecum after restorative cystoprostatovesiculectomy for bladder cancer. PMID- 2224450 TI - Re: Circumcision--which dressing? PMID- 2224452 TI - Thrombolytic therapy in peripheral vascular disease. PMID- 2224451 TI - Infection and the burn patient. PMID- 2224453 TI - Bile acids and the increased risk of colorectal tumours after truncal vagotomy. AB - An association between colorectal cancer and previous peptic ulcer surgery is reported. In a prospective screening study, 100 asymptomatic patients (80 men and 20 women) who had undergone truncal vagotomy at least 10 years previously were investigated by barium enema, colonoscopy and gallbladder ultrasonography. Control data were obtained from forensic autopsy subjects. The incidence of neoplasms greater than or equal to 1.0 cm in the vagotomized group was 14 per cent (11 adenomas, 3 carcinomas) and 3 per cent in controls (P = 0.01). Duodenal bile obtained at endoscopy from 21 vagotomized patients with normal gallbladders and from 21 control patients undergoing endoscopy was analysed by high performance liquid chromatography. The mean percentage of cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA) and lithocholic (LCA) acids in the bile of vagotomized patients was 32.3, 45.6, 20.7 and 1.4 per cent respectively compared with 45.3, 36.2, 17.9 and 0.7 per cent respectively in controls. The increased proportions of CDCA and LCA and decreased proportions of CA in the duodenal bile of vagotomized patients were significant (P less than 0.001; P = 0.02; P = 0.007). Abnormalities in bile acid metabolism may help to explain the increased risk of colorectal neoplasia 10 years after truncal vagotomy. PMID- 2224454 TI - Urinary tissue factor activity in colorectal disease. AB - Procoagulant activity (PCA) in normal urine has been recognized for over 50 years. Although tissue factor (TF) is produced by certain tumours, and is increased in both tumour-associated macrophages and blood monocytes, the possibility that it might also be increased in urine has not been studied in patients with cancer. We have measured urinary PCA in hospital controls without inflammatory or neoplastic disease (n = 79), in patients with rheumatoid arthritis (n = 8), inflammatory bowel disease (n = 19), colorectal cancer (n = 70) and in patients undergoing colonoscopy (n = 50). Urinary PCA was higher (P less than 0.001) in patients with colorectal cancer and inflammatory bowel disease than controls or patients with rheumatoid arthritis. Fourteen (88 per cent) out of 16 colonoscopy patients subsequently found to have carcinoma or inflammatory bowel disease had levels above the control upper quartile, compared with 8 (24 per cent) out of 34 with normal colonoscopy (P less than 0.001). TF inhibitors confirmed the nature of the PCA and Western blotting studies indicated a urinary TF molecular weight of approximately 38,000. These studies provide further evidence of abnormal haemostasis in malignancy and suggest that determination of urinary TF may provide a useful screening test in patients undergoing colonoscopy. PMID- 2224456 TI - Intraoperative testing of colorectal anastomosis can be misleading. PMID- 2224455 TI - Malignant left-sided large bowel obstruction managed by subtotal/total colectomy. AB - Of 60 patients presenting with acute obstructing carcinoma of the left colon, 49 underwent immediate resection either by radical subtotal/total colectomy (31 patients, group I) or by radical segmental resection (18 patients, group II) of whom three had immediate anastomosis after on-table bowel irrigation and 15 had a planned staged procedure. The operative mortality rate was 3 per cent in group I and 11 per cent in group II (not a statistically significant difference). However, substantial differences were found for major morbidity (6 versus 44 per cent in groups I and II respectively; P less than 0.01) and mean length of hospital stay (17 days in group I versus 35 days in group II; P less than 0.05). All three patients who had on-table lavage developed anastomotic leaks which necessitated a second operation to form a stoma. Six patients (19 per cent) in group I required antidiarrhoeal medication in the immediate postoperative period. However, subsequent improvement in stool frequency was noted in all patients. It is concluded that subtotal/total colectomy is an acceptable means of managing patients with obstructing carcinoma of the left colon in that it is associated with a low morbidity and mortality rate and good functional results. PMID- 2224457 TI - Blood transfusion and recurrence of colorectal cancer: the role of platelet derived growth factors. AB - Efforts to explain the possible effects of blood transfusion on the recurrence of colorectal cancer have been based entirely on the immunosuppressive effects of blood transfusion. However, the relationship between solid tumour development and the immune system is inconclusive. We have investigated an alternative mechanism involving the potential role of growth factors in this phenomenon. Using a human fibroblast: [125I]deoxyuridine uptake mitogenesis assay, the relative amounts of growth factor in the plasma of stored blood were measured. There was a progressive increase in mitogenesis from day 0 (n = 6) to day 28 (n = 6; P less than 0.001, Mann-Whitney U test). The effect of growth factors on the development of liver and intraperitoneal metastases was studied in Hooded Lister rats. Following an intraportal injection of 10(5) MC28 tumour cells, the experimental group (n = 25) received 2 ml of syngeneic serum intravenously for 4 days. Likewise, colonic anastomoses were performed on omentectomized rats and the peritoneal cavity seeded with 10(3) cells. The experimental groups (n = 20) received either 2 ml serum intravenously repeatedly or 3 ml serum intraperitoneally (n = 19). There was no significant increase in liver metastases or peritoneal disease following intravenous infusion of serum but serum delivered intraperitoneally resulted in a significant increase in tumour from 22 per cent in the controls to 89 per cent in the study group (P less than 0.01). Growth factors released from platelets following blood loss into the peritoneal cavity may be important in enhancing local recurrence of colorectal cancer. PMID- 2224458 TI - Mastalgia refractory to drug treatment. AB - Management of the patient with mastalgia who fails to respond to first line therapy is a difficult problem and there is a group of patients who do not respond to any therapy. A group of 126 patients with mastalgia who failed to respond to first line therapy and completed further treatment options was studied. The response rate of those with cyclical mastalgia fell to 57 and 25 per cent for second and third line therapy respectively. Equivalent figures for non cyclical mastalgia were 24 and 21 per cent. Danazol maintains a high response rate after the failure of other drugs, whereas the second line response to bromocriptine and evening primrose oil is poor. Unresponsive patients were matched to a group of patients who responded to first line therapy, and reproductive and historical factors were compared using the chi 2 test, but failed to identify which patients would respond to therapy. PMID- 2224459 TI - Experimental study of starch-induced intraperitoneal adhesions. AB - The effects of starch on the development of postoperative adhesions were examined in 144 Sprague Dawley rats. Groups of rats were injected intraperitoneally with suspensions of washings from starched gloves, starch-free gloves and starch-poor washed gloves, and after operative manipulation of the bowel. The incidence of adhesions was greatest (78 per cent) after laparotomy and injections of starch rich washings and least when starch-poor (33 per cent) or starch-free glove suspensions (37 per cent) were used, confirming an advantage for washing gloves or switching to starch-free products. PMID- 2224460 TI - Through-knee amputation in high-risk patients with vascular disease: indications, complications and rehabilitation. AB - During a 10-year period 104 patients (mean age 72 years) had 106 through-knee amputations. Indications for surgery were: limb gangrene, 67 (64 per cent); ischaemic ulceration, 22 (21 per cent); rest pain, 9; knee contractures, 6. Thirty patients had had previous unsuccessful vascular reconstructive surgery and five had had a failed femoral embolectomy. The through-knee disarticulation used lateral skin flaps. The mortality was 21 (20 per cent). Of the 83 survivors, 59 (71 per cent) underwent uncomplicated primary wound healing; 36 (43 per cent) of the survivors were unsuitable for rehabilitation on a prosthesis. The remaining 47 (57 per cent) were walking before discharge 30-130 days (mean 68 days) after amputation. Through-knee amputation is a rapid, relatively bloodless, amputation and is a useful debridement procedure. The many surgical and functional advantages, in conjunction with the recent reports of better rehabilitation compared with the above-knee or Gritti-Stokes amputation, suggests that the through-knee amputation deserves greater consideration. PMID- 2224461 TI - Graft stenosis: justification for 1-year surveillance. AB - In all, 412 femorodistal grafts (femoropopliteal and femorocrural), performed between 1984 and 1988, have been prospectively studied at 6 weeks and 3, 6, 9 and 12 months after operation and at intervals of 6 months thereafter by duplex scanning and intravenous digital subtraction angiography. The overall incidence of stenoses was 16 per cent (femorocrural 20 per cent, femoropopliteal 15 per cent). All stenoses were detected in the first year after operation and none occurred after this. Twenty-four non-haemodynamically significant stenoses were not treated but were followed at intervals of 3 months. Forty-two haemodynamically significant stenoses were detected and secondary procedures were performed in 30 grafts at a mean of 8 months after surgery. Thirteen had percutaneous balloon dilatation and six (46 per cent) remain patent at a mean follow-up of 22 months. Two grafts which occluded within 30 days and three which restenosed at a mean of 8 months had tertiary procedures. Seventeen grafts were surgically revised, nine with patch grafts and eight with bypass grafts. Eleven of these remain patent at a mean follow-up of 30 months. One occluded immediately and three occluded late. Two grafts which restenosed at a mean of 19 months had successful tertiary procedures. In total, seven grafts had tertiary procedures (two had balloon dilatation and five had surgery) and six of these remain patent at a mean follow-up of 13.5 months. In conclusion, 37 procedures have been performed on 30 grafts, of which 23 (77 per cent) remain patent at a mean follow up of 12 months. Approximately one-quarter of femorodistal grafts will develop graft-related stenoses and graft surveillance is worthwhile, but only for the first year after operation. PMID- 2224462 TI - Conservative management of asymptomatic popliteal aneurysm. AB - Historical review shows that the treatment of popliteal aneurysm has developed by trial and error and there is disagreement about the proper management of the symptomless patient. In 1981 a policy of conservative management for asymptomatic popliteal aneurysm was adopted in this unit. Since that time we have also managed nine patients with thrombosed popliteal aneurysms by arteriography and low-dose intra-arterial streptokinase. Six patients treated within 72 h of occlusion achieved significant (70-100 per cent) lysis, but streptokinase was ineffective in those treated 10 or more days after the thrombosis. Of the six patients with significant lysis, three were treated by elective reconstruction and two by anticoagulation. One patient who had significant lysis died. Vascular patency of all five successfully treated limbs was maintained and no limb loss occurred in those who presented late and failed to achieve significant lysis. These results reinforce the view that thrombolysis is the treatment of choice for thrombosed popliteal aneurysms. The low complication rate for asymptomatic popliteal aneurysms and the advent of safe, effective thrombolysis indicate that operation for symptomless popliteal aneurysm is no longer required. PMID- 2224463 TI - Acute limb ischaemia: the place of intravenous streptokinase. AB - Intravenous streptokinase infusions (100,000 units/h) have been used to treat 48 patients, with 50 episodes of acute limb ischaemia who were unlikely to benefit from a surgical approach. These included 17 acute thromboses, 14 late or distal emboli and 19 bypass graft occlusions. Overall, 17 (34 per cent) instances had complete lysis with reappearance of distal pulses and a further 28 per cent had clinical improvement without change in pulse status. Final outcome after 30 days was limb salvage in 60 per cent, amputation in 24 per cent and death in 16 per cent, but this was achieved after eight patients without lysis had vascular reconstructive surgery. Serious complications were infrequent, but included a fatal stroke, a haematemesis and two episodes of distal embolization. The outcome was not related to the duration of ischaemia or the site of occlusion. Lysis was more frequent with emboli (50 per cent) and graft occlusions (47 per cent) than arterial thromboses (6 per cent). Limb salvage was more likely in patients with no neurological deficit in the limb (70 per cent) than if a deficit was present (37 per cent). In conclusion, intravenous streptokinase produced a moderate benefit with low morbidity and has a role in acute limb ischaemia if surgery is inappropriate and intra-arterial lysis unavailable. In particular, selected patients with emboli or graft occlusions without a neurological deficit may be most suitable. PMID- 2224464 TI - On-table pancreatography: importance in planning operative strategy. AB - We describe our experience with 124 on-table pancreatograms performed during 117 operative procedures on 112 patients in a wide variety of clinical settings. Endoscopic retrograde cholangiopancreatography (ERCP) was performed on 84 occasions with a 73 per cent success rate for visualization of the main pancreatic duct. On-table pancreatography (OTP) was performed by one of five different techniques: retrograde, prograde or ambigrade ductography, cystography and ascending loopography after pancreaticojejunostomy. OTP provided important information about the main pancreatic duct when endoscopic visualization was unsuccessful (n = 23), incomplete (n = 17) or not performed (n = 33); there was a failure rate of 4 per cent. In 35 patients either the additional information or discrepancies between ERCP and OTP findings resulted in a change of operative plan (19 extra procedures, 16 altered procedures). Complete ductography was especially helpful in the 63 patients with chronic pancreatitis. OTP is technically simple, free from complications and invaluable for planning operative strategy. PMID- 2224465 TI - Stress in surgeons. AB - A sample of 1000 members of the Association of Surgeons of Great Britain and Ireland was circulated with a postal questionnaire relating to their occupational stressors, their type A coronary-prone behaviour and their mental health. Six hundred and seventy-two (67 per cent) useable forms were returned anonymously. The major individual stressors were: (1) the interference of the job with personal life, (2) general administration, and (3) the number of patients in clinics. Type A behaviour was similar to that of other professional groups. Surgeons showed mean scores significantly higher than the general population on two subscales of the mental health index (free-floating anxiety and hysterical anxiety). The findings for the few female surgeons (2 per cent) were similar to those in men but they did not exhibit raised free-floating anxiety levels. PMID- 2224466 TI - Aetiology of pancreatic cancer. AB - Curative surgery is possible in only a small minority of patients with pancreatic cancer and, to date, responses to chemotherapy and radiotherapy have been disappointing. To make any impact on the incidence of the disease a clearer understanding of its aetiology is required. This review explores present knowledge of the aetiology and epidemiology of pancreatic cancer. PMID- 2224467 TI - Parathyroid autotransplantation. AB - This paper reviews the technique, indications and results of parathyroid autotransplantation. Autotransplantation is most commonly indicated following parathyroidectomy for renal osteodystrophy, but can also be used in primary hyperplastic hyperparathyroidism, re-exploration of the neck and radical neck surgery. The success of the technique ranges from 75 to 100 per cent. PMID- 2224469 TI - Premorphological metabolic changes in human breast carcinogenesis. AB - Malignant breast tissue is characterized by morphological and metabolic changes when compared with normal breast tissue. In this study, the cytochemical measurement of glucose-6-phosphate dehydrogenase (G6PD) activity was used to detect abnormal metabolism in breast tissue and to determine whether abnormal metabolic activity precedes morphological change during human breast carcinogenesis. Normal and benign breast tissue, morphologically normal tissue from cancer-containing breasts, and malignant breast tissue were studied. In malignant tissue, mean(s.e.m.) G6PD activity was significantly increased when compared with normal and benign tissue (9.69(2.3) versus 27.02(1.7) mean integrated extinction (MIE) x 100, P less than 0.01). G6PD activity was increased in morphologically normal tissue from cancer-containing breasts when compared with normal and benign breast tissue from breasts with no known cancer (27.02(1.7) versus 18.42(2.6) MIE x 100, P less than 0.05). These findings suggest that metabolic abnormalities precede morphological changes in breast carcinogenesis. Abnormal metabolism can be detected widely within a cancer containing breast. The detection of such abnormality may prove helpful in identifying patients at high risk of developing breast cancer. PMID- 2224468 TI - Surgery in patients on long-term steroid therapy: a tentative model for risk assessment. AB - Increased morbidity after operation has been associated with long-term steroid therapy. To determine the correlation between steroid therapy and such morbidity, the perioperative course of 55 steroid-treated patients was reviewed: 27 had bronchopulmonary disorders (group P) and 28 had non-pulmonary diseases (group NP). There were six (11 per cent) deaths, of which three were steroid related. Among the 13 non-lethal postoperative complications, eight were considered to be steroid related in group P and one in group NP. The duration of steroid therapy was for a median of 24 months (range 1-408 months) in group P and for a median of 6 months (range 1-240 months) in group NP (P less than 0.01). In contrast, the daily dose of hydrocortisone or equivalent before operation was significantly lower in group P, with a median of 0.51 mg kg-1 day-1 (range 0.20-2.56 mg kg-1 day-1) than in group NP, with a median of 1.20 mg kg-1 day-1 (range 0.23-7.38 mg kg-1 day-1) (P less than 0.01). In conclusion, bronchopulmonary disorders requiring a long duration of steroid therapy are associated with a higher risk of steroid-related complications after surgery. A convenient mathematical model is proposed which may allow a preoperative assessment of surgical risk, using steroid dose and duration of treatment. PMID- 2224470 TI - Selection of patients with internal intussusception of the rectum for posterior rectopexy. PMID- 2224471 TI - Treatment for paraphimosis: the 'puncture' technique. PMID- 2224472 TI - Treatment of trans-sphincteric fistulae by full thickness anorectal advancement flaps. PMID- 2224473 TI - Cholecystectomy through a 5 cm subcostal incision. PMID- 2224474 TI - Localization of impalpable breast lesions: a new device. PMID- 2224475 TI - Epidural analgesia in colonic surgery. PMID- 2224476 TI - Usefulness of anorectal myectomy. PMID- 2224477 TI - Diagnosis and management of mesenteric infarction. PMID- 2224478 TI - Early operative fracture management of patients with multiple injuries. PMID- 2224479 TI - Impact of AIDS on surgery. PMID- 2224480 TI - Vacuum drainage of groin wounds after vascular surgery. PMID- 2224481 TI - Potential hazards of mechanized surgical retractors. PMID- 2224482 TI - Transport animals promoted. PMID- 2224483 TI - Exfoliative vaginal cytology during the oestrous cycle of the cow, after ovariectomy, and after exogenous progesterone and oestradiol-17 beta. AB - Vaginal exfoliative cytology was studied in five normal cyclical Friesian cows over 10 oestrous cycles each. Oestrus was assessed by the use of KaMaR heat mount detectors, whilst progesterone concentrations were measured in the peripheral blood using radioimmunoassay. Apart from oestrus, the exfoliative cytology was not consistent in appearance and did not appear to be influenced directly by the changes in endogenous ovarian steroid hormones. Four of the cows were subsequently ovariectomized and the vaginal exfoliative cytology monitored before and after the administration of 2 g of progesterone in a slow release vehicle and, following a rest period, after the administration of 12.5 mg oestradiol benzoate in oil. Peripheral progesterone and oestradiol-17 beta concentrations were measured in the peripheral plasma. Although the total number of epithelial cells increased after both hormone treatments no specific changes were observed. PMID- 2224484 TI - Serum thromboxane generation by platelets in several domestic animal species. AB - Blood collected from calves, sheep, goats, pigs, dogs, horses, ponies and donkeys, was allowed to clot under standard conditions. Thromboxane B2 generated during the clotting process was measured by radioimmunoassay in serum harvested from each sample. Highly significant differences were found between species and also between genera within a species. Highest concentrations of thromboxane B2 were detected in the dog samples (887.7 +/- 123.7 ng/ml) and lowest concentrations in samples from sheep (2.7 +/- 0.2 ng/ml). The amount of thromboxane produced per unit number of circulating platelets or per unit volume of platelets in each species was not the same and it would appear that platelets from each species have different inherent ability to produce thromboxane under the stimulus applied, or that some species generate thromboxane from other sources during the clotting process. PMID- 2224485 TI - Isometamidium in goats: disposition kinetics, mammary excretion and tissue residues. AB - The pharmacokinetics of the antitrypanosomal drug isometamidium were studied in lactating goats after intravenous and intramuscular administration at a dose of 0.5 mg/kg body weight, in a crossover design at an interval of 6 weeks. Following intravenous administration, the half-life of the disappearance of the drug from plasma during the terminal phase was 3.2 h, and the mean residence time was 2.4 h. The apparent volume of distribution averaged 1.52 l/kg, and the mean total body clearance was 0.308 l/kg/h. After intramuscular administration, the absolute bioavailability was low, averaging 27%. This was consistent with a low mean maximum concentration of 24 ng/ml which occurred after 6 h. No drug was detectable (less than 10 ng/ml) in milk samples collected over a period of 14 days following drug administration by either the intravenous or intramuscular route. In tissues analysed when the goats were killed 6 weeks after administration of the second dose, no drug was detectable (less than 0.4 micrograms/g wet tissue) in the liver, kidney and muscle. However, at the injection site, drug concentrations varied from less than 0.4 to 18.8 micrograms/g wet tissue. PMID- 2224486 TI - Changes in liveweight gain, blood constituents and worm egg output in goats infected with a sheep-derived strain of Trichostrongylus colubriformis. AB - Two groups of goats were dosed with 20,000 and 40,000 sheep-derived strain (SDS) larvae of Trichostrongylus colubriformis respectively. Over a period of 42 days, goats dosed with 40,000 larvae lost more weight than goats dosed with 20,000 larvae. Anaemia was not observed in infected goats, but total serum proteins, albumins and phosphorus fell with infection. PMID- 2224487 TI - Effects of age, environmental temperature and relative humidity on the colonization of the nose and trachea of calves by Mycoplasma spp. AB - Nasal and tracheal swabs sequentially collected from three groups of eight calves between the ages of 1 and 98 days indicated that the nose and trachea were colonized by Mycoplasma spp. during the first weeks of life. Over 92% of all calves harboured Mycoplasma spp. in their noses when they were 2 weeks old, the rate of recovery falling gradually thereafter. The peak period of recovering mycoplasmas from the noses and tracheas of calves was at 6 weeks old. M. bovirhinis, M. arginini and Acholeplasma laidlawii predominated in the nose while M. dispar and M. bovirhinis predominated in the trachea. There was no association between rates of isolation and clinical signs of respiratory disease. There were no significant differences between the frequencies of isolation of Mycoplasma spp. from groups of calves kept under different environmental temperatures and relative humidities. PMID- 2224489 TI - In-vitro antimicrobial susceptibility of Bacteroides and Fusobacterium isolated from footrot in goats. AB - The agar dilution method was used to determine the antimicrobial activity of 17 antimicrobial agents against 132 strains belonging to the genus Bacteroides and 25 strains from the genus Fusobacterium, all isolated from 120 clinical cases of caprine footrot between October 1987 and November 1988. Josamycin, chloramphenicol and rifampin proved to be the most effective antibiotics in vitro. Significant resistance was found to the other antimicrobial agents studied. PMID- 2224488 TI - Mast cells in the bovine lower respiratory tract: morphology, density and distribution. AB - The lower respiratory tract of six 8-day-old calves and six adult cows was fixed in either isotonic formal-acetic-acid or neutral buffered formalin in order to study the morphology, density and distribution of mast cells. They were found at all levels of the tract with the highest density in the major bronchi. Tissues from cows had significantly more mast cells than those from calves. There were significantly more mast cells detected in calf airways fixed with isotonic formal acetic-acid compared with those seen in the same tissues fixed with neutral buffered formalin. Regardless of the age and fixation, mast cells were located predominantly in the alveolar septa and in the lamina propria of airways. They were also commonly encountered within the mucosal epithelium of the trachea. Ultrastructurally, mast cells in bovine airways and lung contained two types of intracytoplasmic granules as described in other species. PMID- 2224490 TI - Characteristics of Staphylococcus aureus from subclinical bovine mastitis in Brazil. AB - A total of 127 Staphylococcus aureus strains isolated from milk samples of cows with subclinical bovine mastitis was examined for biotype, phage pattern, in vitro antibiotic susceptibilities and ability to produce enterotoxins. The majority of the strains showed features consistent with bovine rather than human origin. All strains were sensitive to the antibiotics tested, except penicillin and streptomycin. Enterotoxigenicity was observed in 6 (4.7%) strains and only enterotoxins A and C were produced. PMID- 2224491 TI - Thin sow syndrome (TSS): the effect of amperozide. AB - Sixty sows suffering from typical post-weaning TSS were divided into three groups: (1) 20 as negative controls (NC); (2) 20 as positive controls (PC) treated with vitamins, trace elements and antibiotics; and (3) 20 injected with amperozide (2 mg/kg body weight), a new neuroleptic compound with antistress and anxiolytic properties. Amperozide treated sows fully recovered (P less than 0.05) and 80% became pregnant, while figures for the PC and NC groups were only 15% and 10% respectively. Mortality was up to 50% in the NC, 40% in the PC and only 15% in the amperozide treated group (P less than 0.05). These field results warrant further studies in unravelling the aetiology and prevention of this condition. PMID- 2224492 TI - Plasma beta-endorphin increase following electrical stunning in sheep. AB - Plasma concentrations of beta-endorphin were assayed in 10 sheep during the conscious state and in relation to electrical stunning. There was a 2 fold increase after stunning, and a further elevation following recovery. On this basis it is possible that recovery from electrical stunning at slaughter may cause undue distress, and it is suggested that exsanguination must be carried out promptly. PMID- 2224493 TI - Brain responses to semantic incongruity in bilinguals. AB - Event-related potentials were examined in the first and second languages of bilinguals, and in monolinguals. Stimuli were anomalous sentences presented one word at a time on a CRT monitor. The principal dependent measure was the N400 component, and an accompanying frontal negativity, which provided an estimate of the amount of time the nervous system takes to determine the semantic incongruity of a given word. The results indicate that N400 latency is slightly, but significantly, delayed in bilinguals, with monolinguals having the shortest mean N400 latency, the first language of bilinguals next, and the second language of bilinguals longest. The frontal negativity varied in amplitude somewhat independently of the parietal N400. The amplitude of the frontal negativity was sometimes reduced in the second language, tending to be smaller in those subjects who used their second language the least. Neither N400 nor the frontal negativity varied as a function of age of acquisition of the second language. The results are discussed with reference to the relative automaticity of language in bilinguals, and the sensitivity of N400 to variations in the automaticity of language processing. PMID- 2224494 TI - Reading in callosal agenesis. AB - It has been suggested that deficits in explicit phonological processing are causal in developmental dyslexia. Deficits in such skills have been reported in developmental phonological dyslexia, though not in developmental surface dyslexia. The reading performance of two children with callosal agenesis, who have been previously shown to have impairments on rhyming tasks, are reported. Neither child is dyslexic in the traditional sense, since word reading levels are appropriate for age. However, both children have impaired development of the phonological reading route despite normal lexical skills. The pattern of their reading is therefore comparable to developmental phonological dyslexia. Problems in explicit phonological processing may be causal in the failure to establish an efficient phonological reading route but this is insufficient to create difficulty with word recognition itself. The corpus callosum may be essential for the normal development of a phonological reading route. PMID- 2224495 TI - Repetition and verbal STM in transcortical sensory aphasia: a case study. AB - The repetition performance of a patient (S.T.) with transcortical sensory aphasia is examined in four experiments with particular emphasis on the STM capacities underlying her performance. S.T.'s repetition of word strings exceeding her span (two words) is characterized by good recall of the final items and a strong tendency to lose the initial items in the input string. This pattern contrasts with the serial position effects observed in a phonologically based STM impairment, and it is suggested that a lexical-semantic impairment, also evident in S.T.'s naming and lexical comprehension, contributes to her inability to retain the primacy portions of the input string. Lexical effects obtained in her reproduction of words and nonwords, as well as word strings (Experiments 1 and 2), indicate that under conditions of impaired semantics S.T. is relying on lexical phonological information to repeat. Priming by repeated exposure (Experiment 3) failed to improve her repetition performance, indicating that access to lexical information is brief and dependent on recent phonological input. In Experiment 4, the role of syntactic structure in S.T.'s sentence repetition was examined, and it was shown that syntactic structure affects the recall of order information, but not the number of items recalled. The repetition and verbal STM abilities of this patient, in light of her total language profile, are then evaluated in the context of a language-based view of verbal STM. PMID- 2224497 TI - The effects of processing requirements on neurophysiological responses to spoken sentences. AB - Ten English speaking subjects listened to sentences that varied in sentential constraint (i.e., the degree to which the context of a sentence predicts the final word of that sentence) and event-related potentials (ERPs) were recorded during the presentation of the final word of each sentence. In the Control condition subjects merely listened to the sentences. In the Orthographic processing condition subjects merely listened to the sentences. In the Orthographic processing condition subjects decided, following each sentence, whether a given letter had been present in the final word of the preceding sentence. In the Phonological processing condition the subjects judged whether a given speech sound was contained in the terminal word. In the Semantic processing condition subjects determined whether the final word was a member of a given semantic category. A previous finding in the visual modality that the N400 component was larger in amplitude for low constraint sentence terminations than for high was extended to the auditory modality. It was also found that the amplitude of a N200-like response was similarly responsive to contextual constraint. The hypothesis that N400 amplitude would vary significantly with the depth of processing of the terminal word was not supported by the data. The "N200" recorded in this language processing context showed the classic frontocentral distribution of the N200. The N400 to spoken sentences had a central/centroparietal distribution similar to the N400 in visual modality experiments. It is suggested that the N400 obtained in these sentence contexts reflects an automatic semantic processing of words that occurs even when semantic analysis is not required to complete a given task. The cooccurrence and topographical dissimilarity of the "N200" and N400 suggest that the N400 may not be a delayed or a generic N200. PMID- 2224496 TI - MRI evaluation of the size and symmetry of the planum temporale in adolescents with developmental dyslexia. AB - MRI technique was used to examine the size and symmetry of the plana temporale in 19 dyslexic students in grade 8 and in carefully matched control subjects. The results demonstrated a high frequency of planum symmetry among the dyslexics (70%) whereas symmetry was observed in only 30% of the control subjects. It was not possible to demonstrate any clear association between symmetry/asymmetry of planum temporale and handedness. Word-reading strategies among the dyslexics and control subjects were investigated with computerized tasks where accuracy and naming latency were recorded. All subjects with pure phonological deficits in reading had symmetrical plana temporale indicating a possible neuroanatomical basis for a characteristic symptom of linguistic processing deficiency in developmental dyslexia. PMID- 2224498 TI - Asymmetrical transfer of braille acquisition between hands. AB - Two experiments are presented which demonstrate asymmetrical transfer for tactual recognition of individual braille letters in sighted subjects, a task usually associated with right hemisphere specialization. Right-handers were studied in Experiment 1, left- and right-handers in Experiment 2. Poor transfer of training from the right hand to the left hand was observed for right-handed subjects in both experiments. The same was true for one group of left-handers (who wrote with the "inverted" position). For another group (who wrote with the "noninverted" position), no disadvantage was associated with opposite-hand training for either hand. The role of hemispheric specialization of function in determining the direction of greater transfer is discussed, and it is argued that handwriting posture may be an index of the degree of functional "connectedness" of the two hemispheres in left-handers. PMID- 2224499 TI - Evidence for cortical dysfunction in spasmodic dysphonia: regional cerebral blood flow and quantitative electrophysiology. AB - Cortical function was evaluated in 26 subjects with spasmodic dysphonia. Quantitative topographic electrophysiologic mapping (QTE) was employed to provide quantitative analyses of EEG spectra and auditory and visual long-latency evoked potentials. Single-photon emission computed tomography (SPECT) of the cerebral transit of Xenon-133 was used to evaluate regional cerebral blood flow. Left hemispheric abnormalities in cortical function were found by both techniques in 10 subjects and by at least one technique in 18 subjects. Right hemispheric abnormalities were observed by both techniques in 8 subjects and by at least one technique in 18 subjects. Most patients with cortical dysfunction in one hemisphere had cortical dysfunction in the other, while only 4 subjects had unilateral lesions as found by one of the two techniques. Eight subjects were normal by all measurements. Underlying structural abnormalities were detected by magnetic resonance imaging in 5/24 subjects. However, functional abnormalities (SPECT or QTE) were not observed at sites of structural abnormalities. SPECT and QTE were significantly related in identification of left hemispheric dysfunction (p = .037) with a trend in the right hemisphere (p = .070), and a significant congruence of SPECT and QTE findings occurred in the left anterior cortical quadrant (p = .011). These findings indicate that dysfunction of cortical perfusion and/or cortical electrophysiology is associated with spasmodic dysphonia in the majority of subjects studied. PMID- 2224500 TI - Afferent connections of the thalamic paraventricular and parataenial nuclei in the rat--a retrograde tracing study with iontophoretic application of Fluoro Gold. AB - The origin of the afferents of the thalamic anterior paraventricular and parataenial nuclei (PVA-PT) in the rat was studied with fluorescent retrograde tracing method. After iontophoretic application of Fluoro-Gold into PVA-PT, many labeled cells were found in the medial frontal cortex, ventral subiculum, claustrum, septum, ventral pallidum, thalamic reticular nuc., zona incerta, hypothalamus, central gray, dorsal raphe nuc., parabrachial nuc., and the laterodorsal tegmental nuc. A few cells were labeled in the medial amygdaloid nuc., amygdalohippocampal area, median raphe nuc., and the locus coeruleus. Occasional neurons were labeled in the ventral lateral geniculate nuc., pretectal area, and in the solitary nuc. and the lateral reticular nuc. in the medulla. PMID- 2224501 TI - Presence of VIP fibers of sensory origin in the rat trachea. AB - The presence of vasoactive intestinal peptide (VIP) immunoreactive nerve fibers (LI) in the respiratory tract of mammals is well documented. These fibers are known to originate from parasympathetic postganglionic neurons and to be associated with blood vessels, submucosal glands, and with smooth muscle. We found that, in addition to this, the epithelial layer of the rat trachea also contains VIP-LI fibers. Vagotomy or ligation of the cervical portion of the vagus nerve resulted respectively in a decrease of VIP-LI fibers within the epithelium or in the accumulation of VIP in axons proximal to the site of transection or ligation, whereas no changes were seen in other parts of the trachea. On the other hand, capsaicin pretreatment also caused similar changes to the surgical procedures. These findings indicate that VIP-LI fibers in the tracheal epithelium of the rat are supplied by the sensory ganglia of the vagus nerve. PMID- 2224502 TI - Influences of neonatal and adult exposures to testosterone on the levels of the beta-subunit of nerve growth factor in the neural tissues of mice. AB - In our previous report, we have shown the sex difference in the concentration of the beta-subunit of nerve growth factor (beta-NGF) in the neural and paraneural tissues of mice. In this investigation, we examined the effects of castration of adult males, and of neonatal and/or adult treatments with testosterone on levels of beta-NGF in the several tissues of mice. Castration caused a marked reduction in the levels of serum testosterone and of beta-NGF in the brain, spinal cord and submandibular glands, but not in the pancreas and kidneys. Continuous infusion of testosterone for one week into adult males that had been castrated at 2 months of age restored the level of beta-NGF in the three tissues mentioned above. A single injection of testosterone to 5-day-old female pups to masculinize the brain gave no effect on the level of beta-NGF in any tissue dissected after 4 months. A one week infusion of testosterone into adult females slightly increased levels of beta-NGF in the brain and spinal cord, but the same treatment of adult females given in advance a single dose of testosterone at 5 days of age caused a significant increase in its levels over those of untreated females. These results suggest that neonatal and adult exposures to testosterone can influence the endogenous concentration of beta-NGF in the brain and spinal cord. PMID- 2224503 TI - Axotomy affects density but not properties of potassium leak channels, in the leech AP neurons. AB - Leech AP neurons react to axotomy by increasing excitability and resting potential of the cell body membrane. In a previous report we described single potassium channels contributing to the leak conductance in the soma membrane of AP cells. Here we compare both properties and density of single potassium leak channels in cell-free patches from normal and axotomized AP neurons. We show that properties such as single channel conductance, outward rectification, time constants of open and shut interval distributions and absence of inactivation do not significantly differ between normal and axotomized cells. On the other hand, we find that the number of channels per patch progressively increases with time after axotomy. We conclude that changes in density rather than alterations in properties of single channels can account for the increase in the resting potential, observed after axotomy. PMID- 2224504 TI - Clonidine and phenylephrine injected into the lateral hypothalamus inhibits water intake in rats. AB - It has been demonstrated that peripheral or intracerebroventricular (i.c.v.) administration of the alpha 2-adrenoceptor agonist, clonidine, blocks the water intake induced by several dipsogenic stimuli in rats. In the present investigation we studied the effect of the injection of clonidine, phenylephrine, prazosin or yohimbine into the lateral hypothalamic area (LHA) on the water intake induced by water deprivation or central angiotensin II (AII) in rats. Rats with chronic cannulas implanted into the lateral ventricle and LHA were used. Injection of clonidine or phenylephrine into the LHA reduced the water intake produced by both water deprivation and i.c.v. injection of AII. Previous injection of the alpha 1- or alpha 2-adrenoceptor antagonists, prazosin or yohimbine, into the LHA reduced the antidipsogenic effect of clonidine or phenylephrine injected into the same area. These results suggest that the alpha 1 and alpha 2-adrenergic receptors of the hypothalamus are part of the central inhibitory system for the thirst produced by dehydration or central AII. PMID- 2224505 TI - Effects of anesthesia on efferent phrenic activity in neonatal swine. AB - The effects of two levels of Saffan anesthesia (standard recording level: 2-4 mg/kg/min, and 10X recording level) and a single level of pentobarbital (5 mg/kg) on the power spectral density of efferent phrenic discharge were investigated in piglets aged from less than 1 day to 50 days. The phrenic high frequency oscillation (HFO) was present in decerebrate, unanesthetized piglets and in piglets anesthetized with Saffan, albeit reduced at 10 times recording level, but was absent under pentobarbital. The results indicate that Saffan does not have a significantly depressant effect on the phrenic HFO in developing swine. PMID- 2224506 TI - Suprathreshold brain stimulation activates non-corticospinal motor evoked potentials in cats. AB - In the feline model of the motor evoked potential (MEP) test, a multiphasic spinal cord signal can be elicited in response to bipolar or transcranial brain stimulation. Previous studies have shown that signals produced by threshold stimulation travel mostly in the corticospinal tract. However, from this study we show that suprathreshold stimulation produces very large amplitude MEPs which travel in the ventral funiculus and therefore are most likely associated with extrapyramidal tract activation. The data supporting this conclusion are: (1) apparent conduction velocities of the first two large amplitude peaks are at least 80 m/s with transcranial stimulation; (2) latency of the transcranial MEP at L2 in the cord is less than or equal to 3.50 ms; (3) large amplitude, positive monophasic potentials are recorded in the ventral but not dorsal-lateral funiculus for either bipolar or transcranial MEPs; (4) both bipolar and transcranial MEPs are significantly reduced or abolished by selective lesion of the ventral funiculus. The two tracts which we believe are responsible for mediating the suprathreshold MEP in the cat are the reticulospinal and vestibulospinal tracts. This is significant because suprathreshold MEPs can be used to monitor feline ventral cord function. Furthermore, combining the use of threshold and suprathreshold MEPs may provide a differential diagnostic test for pyramidal vs. extrapyramidal motor function. PMID- 2224507 TI - Repeated low doses of morphine do not induce tolerance but increase the opioid antinociceptive effect in rats with a peripheral neuropathy. AB - In rats with a mononeuropathy, repeated low doses of morphine slightly enhanced its own effect in a paw pressure test of the lesioned limb. While the very effectiveness of morphine in neuropathic rats suggests that at least some nociceptive components of neuropathic pain might be sensitive to opioid receptor mechanisms, the absence of a rapid tolerance in this model indicates that tachyphylactic phenomena do not contribute to the reputed clinical ineffectiveness of opioids in neuropathic pain. PMID- 2224508 TI - Cerebellar evoked potential elicited by stimulation of C-fiber in saphenous nerve of cat. AB - Stimulation of the saphenous nerve above C-fiber threshold strength evoked a field potential which consisted of an early component with latency of 11.8 +/- 3.5 ms and a late component with latency of 312.1 +/- 17.5 ms on the cerebellar cortex. After the A-fibers in saphenous nerve were blocked by the polarizing current selectivity, the stimulation at C-fiber suprathreshold elicited a C-fiber cerebellar evoked potential (C-CEP) with latency of 134.2 +/- 18.4 ms. C-CEP had the maximal amplitude on the vermian lobule VI of the contra- and ipsilateral cerebellar cortex and its phases reversed in the deep layer of this area. It was suggested that the selective C-fiber input could reach the cerebellar cortex and elicit a characteristic evoked potential. However, when A- and C-fiber inputs were elicited simultaneously, C-CEP might be inhibited by the A-fiber input. PMID- 2224509 TI - Delay, discriminatory, and modality specific neurons in striatum and pallidum during short-term memory tasks. AB - The function of the striatum and its integrative capacities is addressed. The activity of single neurons in behaving Macaca mulatta is studied. Two new classes of neurons were found. In the striatum, but not in the pallidum, these neurons were visual modality specific. These neurons may represent a conjunction of sensory, mnemonic and motor information, and may be concerned with decisions about the emission or withholding of movements. The frontal dysfunction hypothesis of cognitive deficits in Parkinson's disease is considered. PMID- 2224510 TI - Alterations in brain hexokinase activity associated with streptozotocin-induced diabetes mellitus in the rat. AB - The effects of streptozotocin-induced diabetes mellitus on the activity of discrete regions of the brain were studied with histochemical localization and photodensitometric quantification of the metabolic enzyme, hexokinase. Two weeks after a single injection of streptozotocin (65 mg/kg, i.p.), plasma glucose and osmolarity levels were elevated, and plasma sodium concentrations were depressed. These changes were reversed in diabetic rats treated with insulin. Accompanying these symptoms of diabetes were significant increases in hexokinase activity in the magnocellular division of the paraventricular nucleus of the hypothalamus (mPVH, 12.1%), the medial subdivision of the nucleus of the tractus solitarius (mNTS, 15.5%), and the commissural subdivision of the NTS (cNTS, 10.9%). An increase, though just below the level of significance, was also observed in the supraoptic nucleus of the hypothalamus (SON, 11.5%). The increases in hexokinase activity were completely reversed in the cNTS (and SON) and only partly reversed in the mPVH and mNTS of insulin-treated diabetic rats. No changes in hexokinase activity were seen in the subfornical organ, medial preoptic area, parvocellular division of the PVH, locus coeruleus, or dorsal motor nucleus of the vagus of diabetic rats. These results reinforce the idea that the brain is not exempt from changes associated with diabetes mellitus and suggest that metabolic alterations in the mPVH (and SON) and two divisions of the NTS are likely related to changes in vasopressin production and blood volume, respectively. PMID- 2224511 TI - Retinal direction-sensitive input to the accessory optic system: an in vitro approach with behavioral relevance. AB - Retinal application of gamma-aminobutyric acid (GABA) antagonists block direction sensitive (DS) responses in turtle in two ways: (1) the selectivity of DS retinal ganglion cells in vitro, and (2) the eye's ability to track the direction of full field image motion. The experiments described below demonstrate that an important locus for retinal slip computation by the accessory optic system (AOS) occurs in the retina. Visual responses were measured physiologically and behaviorally from turtles which had their telencephalon removed. Physiological responses to visual field movement were recorded in the AOS using an in vitro brain preparation. DS responses of single cells were blocked by intravitreal application of bicuculline. The behavioral approach was to measure optokinetic nystagmus (OKN) in lesioned animals. OKN occurred in the absence of the telencephalon, yet was disrupted following an intravitreal injection of bicuculline. Thus, both experimental approaches showed that DS processing exists without the telencephalon, yet is disrupted by GABA antagonists applied to the retina. PMID- 2224512 TI - Mn2(+)-activated aspartate aminopeptidase activity, subcellular localization in young and adult rat brain. AB - The levels of soluble and membrane-bound aminopeptidase activities were assayed in subcellular fractions from young (4 weeks old) and adult (20 weeks old) rat brains, using Asp-2-naphthylamide as substrate. The young rats showed the highest soluble and membrane-bound levels of activity in the microsomal fraction but no differences among fractions were found at 20 weeks of age. The membrane-bound activity was significantly higher than the soluble one in all subcellular fractions of young rats. Soluble activity of the homogenate and the mitochondrial fraction was significantly increased in adult animals when compared to that of younger ones. PMID- 2224513 TI - Perinatal exposure to anoxia alone does not alter the susceptibility to amygdaloid-kindled seizures in the adult rabbit. AB - It is suggested that asphyxia on newborns increases the susceptibility to epileptic syndromes. The effect of perinatal and postnatal anoxia on subsequent seizure susceptibility was assessed by amygdaloid kindling in adult rabbits. Rabbits from 1 day pre-term to 53 days were exposed to 100% N2 for an average of 7 min or until the heart rate was reduced by 70%. Non-anoxic littermates served as controls. At 2 months of age, animals were implanted with bilateral amygdalae electrodes. After a postsurgical recovery period, afterdischarge (AD) thresholds were determined for the electrode sites and a kindling paradigm was performed. There were no significant differences in the rate of kindling in all groups studied (control, anoxic at 1 day pre-term or at term, anoxic at 44 and 53 days). These results demonstrate that perinatal anoxia did not alter the seizure susceptibility in the adult rabbit kindling model. PMID- 2224514 TI - Topography of movement-related cortical potentials is abnormal in Parkinson's disease. AB - We studied the scalp-recorded, movement-related cortical potentials occurring immediately before and after the onset of movement in 5 patients with asymmetric Parkinson's disease. The topographic distribution of the initial slope of motor potential (isMP) was diffuse for voluntary finger movements of the more affected hand but normal for movements of the less affected hand. The frontal peak of motor potential (fpMP) was located more posterior in patients than in normal subjects. The peak amplitudes of the potentials were normal in all patients. The topographic abnormalities might reflect inadequate excitatory activity from the basal ganglia to the primary motor cortex and the supplementary motor area. PMID- 2224515 TI - Differential firing patterns of the peptide-containing cholinergic motor neurons B15 and B16 during feeding behavior in Aplysia. AB - During egestive responses neuron B16 fires at 20 Hz, while neuron B15 is not active. During ingestive responses B16 fires for 0.5-1.0 s at 15-20 Hz, then B15 and B16 fire together, with B15 firing at 7.5-12 Hz. The duration of activity during ingestive responses depends on consumption of food: when food is not consumed, bursts are shorter (e.g. 2 vs 4 s). This study establishes a basis for investigating the role of peripheral neuromodulation under physiologically relevant conditions. PMID- 2224516 TI - Partial involvement of monoamines and opiates in the inhibition of rat spinal nociceptive neurons evoked by stimulation in midbrain periaqueductal gray or lateral reticular formation. AB - In rats anesthetized with sodium pentobarbital, we tested the effects of systemic or intrathecal administration of the opiate antagonist naloxone, the serotonergic antagonist methysergide, or the adrenergic antagonist phentolamine, on inhibition produced by electrical stimulation in midbrain periaqueductal gray (PAG) or lateral reticular formation (LRF) of the responses of single lumbar dorsal horn neurons to noxious heating (50-54 degrees C, 10 s) of hindpaw skin. Systemically administered naloxone (1-10 mg/kg i.v.) reduced (greater than 20% below predrug inhibition) inhibition from PAG and/or LRF in 5/12 units and had no effect in the remainder. Systemic methysergide (2-6 mg/kg i.v.) selectively reduced PAG-evoked inhibition in 6 units, while inhibitions from both PAG and LRF stimulation were reduced in one unit and unaffected in 8 units. Systemic phentolamine (2-4 mg/kg) reduced LRF-evoked inhibition in 4 units, while inhibitions from PAG and LRF were reduced in one unit and unaffected in 5. Intrathecally applied methysergide reduced or abolished PAG-evoked inhibition in 8/16 units and reduced or abolished LRF-evoked inhibition in 6/14 units. Reductions in the level of inhibition were reversible in one-half of the cases, whereas they persisted for over 2 h in the remainder. The mixed effects of both systemically and intrathecally administered drugs suggest that monoamines and opiates may be partly involved in spinal inhibitory mechanisms activated from the midbrain. PMID- 2224517 TI - Brown adipose tissue thermogenesis is activated by electrical and chemical (L glutamate) stimulation of the ventromedial hypothalamic nucleus in cold acclimated rats. AB - Experiments were conducted to determine if both electrical and chemical stimulation of the ventromedial hypothalamic nucleus (VMH) could activate brown adipose tissue (BAT) thermogenesis. Age-matched, room-acclimated (21 degrees C) and cold-acclimated (4 degrees C for 3 weeks prior to testing) male Sprague Dawley rats were given unilateral electrical or chemical stimulation to the VMH by way of a 'chemotrode apparatus'. The devised 'chemotrode' allowed both electrical stimulation (insulated piano wire stimulating electrode) and chemical stimulation (23 gauge stainless steel intracranial cannula of equal length) to be performed at the same VMH site using a common 19 gauge stainless steel outer guide tube. The first unilateral VMH electrical stimulation (0.5 ms pulse, 50 Hz and 120 microA for 30 s) caused no significant rise in interscapular brown adipose tissue temperature (TIBAT) colonic (Tc) or tail surface temperatures (Tt), compared to respective prestimulation control values in rats acclimated to 21 degrees C. In the 4 degrees C-acclimated group the first VMH electrical stimulation caused a significant rise in IBAT temperature. L-Glutamate administration to the same VMH site (60 nmol in 600 nl volume) also caused a significant increase in IBAT temperature in the 4 degrees C but not the 21 degrees C-acclimated rats. The rise in IBAT temperature following the L-glutamate injection to the 4 degrees C-acclimated group was similar to that found following the first electrical stimulation to this group. Interestingly, a second unilateral electrical stimulation of the VMH to 4 degrees C-acclimated rats could not evoke a similar increase in IBAT temperature suggesting that overall L glutamate was acting in vivo as an excitotoxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224519 TI - Latex nanosphere delivery system (LNDS): novel nanometer-sized carriers of fluorescent dyes and active agents selectively target neuronal subpopulations via uptake and retrograde transport. AB - A wide range of latex particles are described which are capable of carrying high concentrations of fluorescent dyes, drugs, and photoactive agents selectively to subpopulations of neurons in vitro and in vivo. Particle size, charge, and concentration were all found to influence uptake into cultured neurons or retrograde transport in vivo. Chromophore loadings of greater than 14% (w/w) were obtained. Incorporation of a photoactivated dye (chlorin e6) into the polymer did not compromise the ability of the dye to produce singlet oxygen following light exposure. We refer to this unique family of latex particles as the latex nanosphere delivery system (LNDS). The LNDS will be usefull for studies of neuroanatomy and nervous system development, as well as more general areas of biomedical research where it is desirable to selectively label subpopulations of cells. The LNDS also offers a means of providing targeted delivery of drugs or photoactive agents to selected subpopulations of cells; this will allow experimentation not currently possible using any existent methodology. PMID- 2224518 TI - Antagonism of the gerbil's sweetener and Polycose gustatory responses by copper chloride. AB - Antagonism of the gerbil's whole chorda tympani nerve taste responses by CuCl2 was studied. A 30 min pretreatment of 0.1 mM CuCl2 suppressed responses to single concentrations of the following sweeteners: L-alanine, L-proline, D-tryptophan, 6 chloro-D-tryptophan, L-valine, glycine, sucrose, maltose, lactose, tetrachloro galacto-sucrose, glucose, fructose, methyl alpha-D-glucopyranoside, glycerol, sorbitol, sodium saccharin, L-4'-cyano-3'-(2-2-2-trifluoro acetamido)succinanilic acid, phenethyurea, and stevioside. The responses to L-serine and the starch hydrolysate, Polycose were depressed to a lesser degree. The responses to glycine HCl and NaCl were slightly suppressed by CuCl2. The 0.1 mM CuCl2 had no effect on the shape of the sucrose concentration-response curve or its 1/2 maximal response (CR50), but did suppress the maximum response (Rmax), characteristic of non competitive antagonism. Our work suggests the presence of 2 separate receptor sites on the gerbil's taste receptor cell membrane, one of which interacts with sugar sweeteners and most other non-sugar sweeteners and the other with Polycose. PMID- 2224520 TI - Cardiovascular responses to electrical stimulation of the ventrolateral medulla of the spontaneously hypertensive rat. AB - Cardiovascular responses to electrical microstimulation of the ventrolateral medulla were investigated in both Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) under pentobarbital anesthesia. The threshold intensity required to elicit a change in blood pressure (BP) and the cardiovascular responses in these two groups of rats upon electrical stimulation were compared. It was found that the region with the lowest threshold intensities was located in the rostral ventrolateral medulla (RVL) and the threshold intensities were much lower in SHR than in WKY. Electrical stimulation of this brain region also resulted in a greater increase in BP during stimulation in SHR, compared to control. In SHR, upon termination of stimulation, the BP dropped to a level above the pre-stimulation level and this was followed by a prolonged, sustained elevation in BP before returning to the control level, whereas in WKY, the BP showed an initial drop to below the pre-stimulation level and then returned to the control level. These results suggest an enhanced responsiveness to electrical stimulation in SHR. Although the heart rate (HR) increased to a similar extent during electrical stimulation in both groups of rats, upon termination of stimulation WKY exhibited bradycardia followed by tachycardia before the HR returned to the pre-stimulation level, whereas SHR exhibited tachycardia which was maintained for a substantial period of time before returning to the pre stimulation level. The results suggest a lower baroreceptor sensitivity in SHR. The change in HR/change in BP was smaller in SHR than in WKY, suggesting that the increase in HR may not contribute to the increase in BP during stimulation as much in SHR as in WKY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224521 TI - Evidence for the in vivo polymerization of ependymin: a brain extracellular glycoprotein. AB - Ependymin, a glycoprotein of the brain extracellular fluid, has been implicated in synaptic changes associated with the consolidation process of long-term memory formation and the activity-dependent sharpening of connections of regenerating optic nerve. In vitro experiments have demonstrated that ependymin has the capacity to form fibrous insoluble polymers (FIP) when the solvent Ca2+ concentration is reduced by the addition of EGTA. Such products, once formed, do not dissolve in 2% sodium dodecyl sulfate (SDS) in 5 M urea. This property was used to develop a method for isolating brain FIP. A reproducible quantity of FIP was found in goldfish and mouse brain. This was highly concentrated in the synaptosomal fraction and had identical immunoreactivity properties to FIP obtained by the polymerization of pure ependymin in vitro as well as a cross reactivity to other protein components of the extracellular matrix such as fibronectin and laminin. Labeling studies with [35S]methionine showed that labeled FIP aggregates are synthesized in vivo and become associated with the synaptosomal fraction. A comparison of the amino acid sequence of ependymin with those for proteins of the extracellular matrix indicated that common sequences 5 6 amino acids long exist in the molecules. These homologies may explain why antibodies to fibronectin, laminin and tubulin can recognize the FIP prepared from pure ependymin. These results suggest that ependymin can polymerize in vivo to form FIP aggregates which have similar immunoreactivity properties to major components of the brain extracellular matrix. PMID- 2224522 TI - Effects of lesions of a sexually dimorphic nucleus in the preoptic/anterior hypothalamic area on the expression of androgen- and estrogen-dependent sexual behaviors in male ferrets. AB - The male nucleus of the preoptic/anterior hypothalamic area (MN-POA/AH) is a sexually dimorphic structure present in male, but not in female ferrets. Ovariectomized female ferrets given increasing dosages of estradiol benzoate (EB) normally run faster towards a stud male in an L-maze (i.e. become more proceptive). In two separate experiments, only gonadectomized males with bilateral damage to the MN-POA/AH following large or small electrolytic lesions approached stud males more quickly in response to EB. By contrast, males which received sham lesions, unilateral large POA/AH lesions, or bilateral lesions which missed the MN-POA/AH on at least one side failed to show EB-induced reductions in approach latencies in pre- or post-operative tests. Males with large POA/AH lesions also displayed significant post-operative decrements in masculine sexual behaviors during treatment with a high dose of testosterone propionate (TP). Less severe, but statistically significant deficits in masculine coital performance were also observed in males with small lesions which damaged the MN-POA/AH bilaterally; however, the ability of these males to achieve intromissions appeared normal. Together, these results suggest that the MN-POA/AH of the male ferret exerts an inhibitory influence on estrogen-dependent proceptive responsiveness, but play only a minor role in the control of masculine coital behavior. PMID- 2224523 TI - Cell culture of cryopreserved human fetal cerebral cortical and hippocampal neurons: neuronal development and responses to trophic factors. AB - Past knowledge of the human brain at the cellular and molecular levels has come largely from studies of postmortem fixed tissue or by way of extrapolation from studies of lower mammalian species. The ability to study living human brain neurons would provide a new avenue for further insight into mechanisms operative in human brain development, function, and disease. The present study established procedures for the cryopreservation and culture of human fetal cerebral cortical and hippocampal neurons, and characterized the development of the cells in culture. The predominant cell type in both cortical and hippocampal cultures was pyramidal-like neurons that extended one long axon-like process and a few minor dendrite-like processes. Bipolar and stellate cells, as well as astrocyte-like glia were also present in cultures from both brain regions. Fibroblast growth factor (FGF), but not nerve growth factor (NGF), enhanced long-term neuronal survival in both cerebral cortical and hippocampal cultures. Immunocytochemistry demonstrated the presence of both FGF- and NGF-like immunoreactivities in neurons and glia, from both cerebral cortex and hippocampus, suggesting that these endogenous growth factors may play roles in human fetal brain development. The ability to cryopreserve large numbers of viable dissociated human fetal brain neurons, and subsequently study them in cell cultures, provides new opportunities to understand dynamic aspects of the human brain at the cellular and molecular levels. PMID- 2224524 TI - Characterization of a glucocorticoid-sensitive hippocampal protein. AB - Increased synthesis of a rat hippocampal protein with an apparent molecular weight (Mr) of 35,000 Da occurs in response to elevation of serum corticosterone levels. Subcellular fractionation has localized this protein in the cytosol. Two dimensional gel electrophoresis indicated that this protein has an isoelectric point (IEP) of 6.6. A similar protein in liver has a slightly higher Mr and an IEP of 6.8. Increased synthesis of one additional hippocampal protein with an Mr of 46,000 Da and an IEP of 6.2 and of two other liver proteins, one with an Mr of 53,000 Da and an IEP of 6.2 and the other with an Mr of 45,000 Da and a range of IEPs from 8.7 to 7.8, was also seen after injection of corticosterone into rats. One possible identity of the 35,000 Da protein is glycerol 3-phosphate dehydrogenase (GPDH), based upon the reported Mr and IEP of this enzyme. The 35,000 Da hippocampal protein co-eluted from a gel filtration column with GPDH activity. No alteration of hippocampal GPDH activity was seen in intact rats 4 or 24 h after injection of either corticosterone or the type II receptor-specific agonist RU 28362. However, daily administration of corticosterone to rats beginning 10 days after adrenalectomy returned hippocampal GPDH activity to normal values after 2-3 days. In contrast, synthesis of the 35,000 Da protein was maximally increased 4 h after a single injection of steroid and not elevated at later times. PMID- 2224525 TI - Muscimol injections in the medial septum impair spatial learning. AB - These experiments examined the role of GABAergic systems in modulating septohippocampal cholinergic influences on learning. Microinjections of the GABA(A) agonist muscimol (0.5, 1.0 or 5.0 nmol) or physiological saline were administered (0.5 microliters) into the medial septum of rats via chronically implanted cannulae just prior to daily training in the Morris water maze spatial learning task. The animals received 3 training trials on each of 4 days. The escape latencies of rats trained with a submerged escape platform at a fixed location were significantly shorter than those trained with a randomly located platform. Rate of learning of the fixed location was significantly impaired in rats given pretraining muscimol injections in the medial septum at doses (1.0 and 5.0 nmol) that significantly reduced hippocampal high-affinity choline uptake (HACU). Analyses of responses on a probe trial with no pretraining injections and no platform revealed that, in comparison with controls, animals that had received muscimol prior to each training session were likely to swim in the region where the platform had been located. The finding that muscimol-injected rats were subsequently able to learn the task when trained without muscimol injections indicates that the acquisition impairment was not due to a lasting effect of the drug injections. Our results are consistent with the view that the septal GABAergic modulation of the septohippocampal cholinergic pathway is involved in regulating the acquisition of spatial information. PMID- 2224526 TI - Protocerebral circadian pacemakers in crayfish: evidence for mutually coupled pacemakers. AB - Similar to intact crayfish, animals with an isolated protocerebrum-eyestalk complex, exhibit competent circadian rhythms in the electroretinogram (ERG). The ERG rhythms of the two eyes remain in phase after isolation of the protocerebrum but can be desynchronized after surgical bisection of the protocerebrum. The desynchrony of the two ERG rhythms reveals the existence of at least two circadian pacemakers in the eyestalk-protocerebrum complex. In addition, the fact that desynchrony of the ERG rhythms only occurs in bisected preparations suggests that pathways between the protocerebral lobes normally couple the two pacemakers. PMID- 2224527 TI - Potassium currents recorded in type I carotid body cells from the neonatal rat and their modulation by chemoexcitatory agents. AB - Whole cell patch clamp recordings were made from type I cells of the neonatal rat carotid body, isolated and maintained in primary culture for up to 48 h. Depolarizing voltage steps applied from a holding potential of -70 mV evoked outward currents positive to approximately -30 mV. Currents were strongly blocked by extracellular tetraethylammonium (25 mM), and were therefore attributed to activation of voltage-dependent K+ channels. Currents were also suppressed by 4 aminopyridine, removal of extracellular Ca2+, and replacement of extracellular Ca2+ with Ba2+. These results suggest there are Ca2(+)-dependent and Ca2(+) independent components of the K+ currents. No evidence was found to suggest that ATP-sensitive K+ channels were present. The effects of 3 chemoexcitatory agents (NaCN, almitrine and reduced extracellular pH) on K+ currents in isolated type I cells were investigated. All three agents suppressed K+ currents to similar degrees. The effects of lowered pH and NaCN were reversible, and NaCN-induced reductions occurred regardless of the presence of intracellular ATP. The effect of almitrine was irreversible for up to 30 min of recording. It is concluded that the reduction of K+ currents by chemoexcitants may play a role in the mechanism of chemotransduction in the carotid body. PMID- 2224528 TI - A subtype of cerebellar Golgi cells may be cholinergic. AB - In cerebellar sections of the feline brain processed for choline acetyltransferase-like immunoreactivity, a population of distinctly stained cells was discovered in the granular layer of the cortex in both vermis and hemispheres. Their position and morphology qualify them as Golgi cells, but their density indicated that they comprise less than 5% of all cerebellar Golgi cells. Varicose immunoreactive fiber nets in all cortical layers also contribute to seemingly widespread cholinergic systems in the cerebellar cortex. PMID- 2224529 TI - Distribution of 'non-specific' cholinesterase histochemical staining in the dorsal thalamus: a comparative study in rodents. AB - Histochemical studies in rat dorsal thalamus demonstrate that 'non-specific' cholinesterase (ChE) enzyme activity is characteristic of neurons of the anterior dorsal (AD) and reuniens (Re) nuclei and in a cell group found as part of the central lateral (CL) and lateral dorsal (LD) nuclei. Extra-somatal ChE staining also is seen in the anterior ventral (AV) nucleus. Parallel histochemical studies in other rodents reveal slight ChE activity in neurons of the mouse AD and LD, but not in other thalamic nuclei. The dorsal thalami of hamsters, gerbils and guinea pigs show no detectable cellular staining of ChE, although low levels of extra-somatal ChE appear in AV and the internal medullary lamina. These data indicate that 'non-specific' cholinesterase activity is not found commonly in neurons of the dorsal thalamus and prominent ChE staining may be unique to the laboratory rat. PMID- 2224531 TI - Characterization of oxytocin immunoreactivity in human sympathetic paravertebral ganglia. AB - Immunoreactive oxytocin (IR-OXT) detected in extracts of human lumbar sympathetic paravertebral ganglia was characterized by high-performance liquid chromatography (HPLC). The immunoreactive substance was found to elute at the same position as the reference preparation of oxytocin (OXT). The results revealed the presence of chromatographically identified OXT in human sympathetic ganglia. PMID- 2224532 TI - Precursor of respiratory pattern in the early gestation mammalian fetus. AB - Recordings of respiratory muscle activity in fetal lambs from early in gestation provide insight into the organization of the central pattern generator for respiration in mammals. Evidence presented here is consistent with the recent hypothesis that production of the respiratory pattern involves two separate neural modules: one, the 'rhythm' module, which specifies the respiratory cycle and another, the 'form' module, which creates the characteristic shape of each burst of activity within this cycle. The rhythm module is already functional when gestation is 35% complete while the form module appears to be constructed gradually over the second half of gestation. PMID- 2224530 TI - The interpeduncular nucleus excites the on-cells and inhibits the off-cells of the nucleus raphe magnus. AB - The interpeduncular nucleus (IPN) was stimulated electrically while single-cell activity was recorded in the nucleus raphe magnus (NRM) of rats under pentobarbital anesthesia. Two classes of NRM cell were examined, those inhibited (off-cells) and those excited (on-cells) by noxious mechanical skin stimulation. Off-cells (92%) were found to be inhibited by IPN stimulation, whereas on-cells (50%) were excited. Based on previously suggested roles for the NRM neurons, we argue that both effects are hyperalgetic. PMID- 2224533 TI - Direct projections from the anterior and tuberal regions of the lateral hypothalamus to the rostral part of the pineal complex of the rat. An anterograde neuron-tracing study by using Phaseolus vulgaris leucoagglutinin. AB - The anterograde tracer, Phaseolus vulgaris leucoagglutinin, was injected into the lateral hypothalamic division of the Wistar rat. After 7 days of survival the animals were fixed by perfusion, and cryostat sections processed for visualization of the tracer by immunohistochemistry. Injections into the anterior and tuberal regions of the lateral hypothalamic division labeled neurons which projected caudally to the rostral part of the pineal complex, e.g. the deep pineal gland and the pineal stalk. Labeled fibers were in this study not observed in the superficial pineal gland. Due to the direct innervation of the lateral hypothalamic region from the retina and the involvement of this area in circadian rhythmicity, the projections, demonstrated in this study, from the lateral hypothalamic region to the pineal gland are suggested to transmit impulses which modulate the circadian activity of the rat pineal gland. PMID- 2224535 TI - Retinal ganglion-cell densities and soma sizes are unaffected by long-term monocular deprivation in the cat. AB - Three cats were raised with monocular deprivation for 5.2-7.2 years, and ganglion cell densities and soma sizes were measured in their flat-mounted retinae. The retinae were Nissl-stained so that ganglion cells could be measured whether or not they maintained normal central projections. Measurements were made in the area centralis, peripheral binocular segment, and monocular segment of the retinae. There were no significant differences between the deprived and non deprived retinae in the densities or soma-sizes of alpha cells or other (non alpha) ganglion cells at any of these retinal locations. These results support the view that the most distal effects of monocular deprivation occur at the retino-geniculate contact, and they suggest that even after long-term monocular deprivation, effects in the lateral geniculate nucleus do not produce secondary, retrograde changes in the retina. PMID- 2224534 TI - Cellular localization of proenkephalin mRNA and enkephalin peptide products in cultured astrocytes. AB - To identify the possible cellular sites of opioid gene expression during ontogeny, proenkephalin mRNA and enkephalin peptide expression were examined, respectively, by in situ hybridization and immunocytochemistry in organotypic explants of rat cerebellum and in astrocyte-enriched cultures of murine cerebral hemispheres. High levels of proenkephalin mRNA and enkephalin immunoreactivity were detected in immature cells identified as astrocytes. Double-labeling studies combining in situ hybridization and immunocytochemical localization of the astrocytic marker, glial fibrillary acidic protein, provided direct evidence that proenkephalin mRNA is expressed by astrocytes in culture. Based on previous studies that Met-enkephalin can inhibit astrocyte growth in vitro, the present results suggest that proenkephalin gene expression by astrocytes is important during central nervous system maturation. PMID- 2224536 TI - Vasoactive intestinal peptide affects the GABAergic system in the hypothalamic pituitary axis. AB - The effect of a specific antiserum against vasoactive intestinal peptide (VIP) on GABA in the hypothalamic-pituitary axis was studied. The administration of anti VIP serum (A-VIP) increased anterior pituitary GABA concentration in control rats, but decreased this neurotransmitter in rats with hyperprolactinemia induced by acute or chronic treatments with estrogens, or by the implanting of anterior pituitary glands under the kidney capsule. Besides, the injection of the A-VIP serum in the morning in proestrous rats causes a decrease in anterior pituitary GABA concentration, measured in the afternoon of the same day. The in vitro effect of A-VIP and VIP on endogenous GABA release from hypothalamic fragments and on anterior pituitary GABA concentration was studied. A-VIP increased both basal and high K(+)-evoked GABA effluxes whereas VIP produced a decrease in evoked GABA efflux from hypothalamic fragments. Furthermore, A-VIP inhibited the normal degradation of GABA that occurs in the isolated gland whereas VIP increased it. These results suggest that VIP modifies hypothalamic GABA release and anterior pituitary GABA concentration. PMID- 2224537 TI - Estradiol in the striatum: effects on behavior and dopamine receptors but no evidence for membrane steroid receptors. AB - Estradiol was applied directly to the striatum of ovariectomized female rats by a unilateral intracerebral cannula for three hr or four days. Following four days of estradiol treatment, rats increased the number of rotations in the direction away from the side of the hormone treatment. Cholesterol-treated animals did not change their rotational behavior. Dopamine receptors were assayed in the same animals by autoradiography; D2 receptors increased on the hormone-treated side relative to the untreated side after four days of treatment, only in the lateral striatum. D1 dopamine receptors did not change. The D2:D1 receptor ratio was related to the direction of rotation. Measurements of membrane fluidity with a fluorescent probe revealed no effect of estradiol on striatal membrane fluidity. Membrane proteins were labeled with estrogen agonist and antagonist affinity labels and analyzed by gel electrophoresis, but no saturable membrane binding sites were detected. The results indicate that estradiol acts directly in the striatum to affect behavior and dopamine receptors, but the neurochemical mechanisms remain to be determined. PMID- 2224538 TI - Effects of serotonin on the hypothalamic-pituitary GABAergic system. AB - The effects of serotonin (5-HT) and its precursor, 5-hydroxytryptophan (5-HTP) on the GABAergic system in the mediobasal hypothalamus (MBH) and the anterior pituitary were studied. The IP administration of 5-HTP produced a transient increase (only at 45 min after the injection) in glutamate decarboxylase activity (GAD) of MBH and in GABA concentration in anterior pituitary. Besides, 5-HTP administration increased the in vitro evoked GABA release from MBH. The administration of 5-HTP to hypophysectomized rats partially reversed the inhibitory effects of hypophysectomy on GABA concentration in MBH. We also examined the direct effect of 5-HT on some parameters on the hypothalamic GABAergic system. The presence of 5-HT in the incubation medium increased GAD activity and evoked GABA release from MBH. These observations indicate that the serotoninergic stimulation of the hypothalamic GABAergic system could be a direct effect which may, at least partially, be independent of the feedback mechanism induced by prolactin on the GABAergic neurons. The serotoninergic increase of prolactin secretion could be accomplished through stimulation of the hypothalamic GABAergic transmission. PMID- 2224539 TI - Effect of haloperidol on immunoreactive neuropeptide Y in rat cerebral cortex and basal ganglia. AB - To clarify the dopaminergic regulation of neuropeptide Y (NPY) neurons, the effect of haloperidol on NPY in basal ganglia and the cerebral cortex of the rat brain was investigated by sensitive radioimmunoassay and immunocytochemistry using antiserum against rat NPY. After repeated intraperitoneal injections of haloperidol (5 mg/kg) for 6 days, the content of immunoreactive NPY was significantly decreased in the caudate-putamen, but significantly increased in the lateral prefrontal cortex. After treatment for 21 days, the content of immunoreactive NPY in the caudate-putamen remained significantly low, but the extent of change in the lateral prefrontal cortex diminished. In the medial prefrontal cortex, piriform cortex, parietal cortex and nucleus accumbens, no significant changes were found after treatment for either 6 or 21 days. These findings were compatible with those obtained by immunocytochemistry using the same antiserum: an increase of immunoreactive fibers and terminals in the lateral prefrontal cortex and their decrease in the caudate-putamen. However, in the nucleus accumbens the density of immunoreactive fibers and terminals was decreased in the rostral portion, but not in the caudal portion after haloperidol treatment for 6 and 21 days. These findings suggest that dopaminergic afferents region-specifically regulate dopamine-sensitive NPY neurons in the rat brain. PMID- 2224540 TI - Changes in retention of a visual discrimination task following unilateral and bilateral transections of temporo-entorhinal connections in rats. AB - In a previous study, it was shown that the lateral entorhinal cortex (LEC) in the left hemisphere contains higher concentration of glutamate than in the right hemisphere. The purpose of the present study was to examine potential relationship between this neurochemical asymmetry and behavior. Rats with either left, right, or bilateral transections of the fiber connections between the temporal cortex and LEC were tested for postoperative retention of a visual discrimination task. Because histological verification of lesions was crucial in this study, analyses of neurochemistry had to be omitted. The results showed that both left and bilateral lesions resulted in impaired retention, but the bilateral group was even more impaired than the left group. The rats with lesions in the right hemisphere, however, used fewer trials to reach the learning criterion than the control group, but they did not make fewer errors than the controls. The results are discussed in terms of lateralization of mnemonic processes. PMID- 2224541 TI - Axonal guidance of adenosine deaminase immunoreactive primary afferent fibers in developing mouse spinal cord. AB - This study examined the precision of central fiber growth in a subpopulation of dorsal root ganglion neurons in developing mouse spinal cord. Immunohistochemical techniques using a monospecific, polyclonal antiserum to mouse adenosine deaminase (ADA) were utilized to label a population of primary sensory afferents that have been found to exclusively innervate laminae I and II of the dorsal horn in adult mice. Initial growth of ADA-immunoreactive (ADA-IR) primary afferents occurred very early in development, embryonic day 10 (E10), a time coincident with the earliest settling time of dorsal root ganglion neurons. Adenosine deaminase immunoreactive primary afferents were observed throughout the cross sectional area of the primordial dorsal funiculus (DF) as early as E10. Immunostained fibers remained quiescent in the DF during its growth and separation into the tract of Lissauer and dorsal column pathway. By E15, the two pathways had formed and ADA-IR fibers were observed exclusively in the tract of Lissauer. This segregation of fibers remained throughout development and reflected the adult pattern. Growth was reinitiated at E16 when the fibers advanced into the dorsal horn and proceeded directly to laminae I and II mimicking their adult distribution. Exuberant fiber growth was not detected throughout their development. These results strongly suggest that ADA-IR fibers exhibit precise fiber guidance to a preferred pathway, the tract of Lissauer, and accurate laminar innervation of the dorsal horn. PMID- 2224542 TI - Hippocampal muscarinic supersensitivity after AF64A medial septal lesion excludes M1 receptors. AB - Stereotaxic injection of AF64A, into the medial septum of the rat, resulted in significant loss of presynaptic cholinergic markers in this structure. No significant change was observed for the presynaptic neuronal markers for dopamine and serotonin-containing neurons in either the medial septum or hippocampus. The AF64A lesion also resulted in a significant reduction of muscarinic receptors as demonstrated by a loss of [3H]QNB binding in the medial septum. Subtype analysis showed the decrease of receptor binding in the medial septum to be due to a loss of M1 receptors as well as other muscarinic receptor subtypes. In the hippocampal formation, [3H]hemicholinium-3 binding was significantly reduced in the molecular layer of the dentate gyrus, and in the stratum oriens and stratum radiatum of the hippocampus. AF64A lesion resulted in a significant increase (Bmax) in non-M1 muscarinic receptors in hippocampal stratum oriens, in areas CA2, CA3, and CA4. AF64A lesion of the medial septum did not result in muscarinic receptor alterations in any other region of the hippocampal formation examined. These results indicate that postsynaptic muscarinic receptors in the stratum oriens of the CA2 to CA4 region of the hippocampus mediate primarily the function of the cholinergic cell bodies of the medial septum. These receptors are not of the M1 subtype. PMID- 2224543 TI - Gerbil hippocampal extracellular glutamate and neuronal activity after transient ischemia. AB - In order to elucidate the role of glutamate in the pathogenesis of delayed neuronal death, we analyzed changes in extracellular levels of glutamate induced by transient ischemia in the Mongolian gerbil hippocampus by a new brain microdialysis method combined with an enzymatic cycling technique. We also studied the effect of this change in glutamate on CA1 spontaneous neuronal discharges. The level of glutamate significantly increased during the 5 min of ischemia and during the first 5 min of recirculation. However, neuronal hyperactivity anticipated as a result of the increased extracellular glutamate was not observed. Spike discharges disappeared during and shortly after 5 min of ischemia; CA1 spontaneous spike discharges reappeared about 15 min after the recirculation. The frequency and amplitude of the discharges of CA1 neurons returned to normal by 30 min of the recirculation. However, the pattern of discharges was different from that recorded before the ischemia. CA1 neurons were found dead 4 days after the ischemia. Brief exposure to toxic concentrations of glutamate may cause the delayed neuronal death. PMID- 2224545 TI - An inexpensive guide cannula and collar for microdialysis experiments. AB - Microdialysis experiments often require that a dialysis probe be fixed into position within the brain during a testing trial but that the probe be easily removed and precisely repositioned within the brain site on subsequent tests. The present paper describes an inexpensive guide cannula and locking collar that is easily fabricated for such experiments. PMID- 2224544 TI - Effects of paraventricular hypothalamic microinjections of phenylpropanolamine and d-amphetamine on mash intake in rats. AB - The present experiment compared the effects of unilateral microinjections (40, 80 and 160 nmol/0.5 microliter) of phenylpropanolamine (PPA: d,l-norephedrine) and d amphetamine sulfate within the paraventricular hypothalamus (PVN) on consumption of a palatable sweetened-mash diet in 15-hour food-deprived adult male rats. Intracranial microinjections were administered 5 minutes prior to each 30-minute feeding trial. PPA, at a dose of 160 nmol, suppressed feeding by 42%, whereas a similar dose of amphetamine suppressed feeding by 49%. Amphetamine or PPA doses of 40 and 80 nmol were without significant effect on feeding behavior. A relatively high dose of 160 nmol amphetamine was required to suppress feeding after injection into the PVN whereas much lower amphetamine concentrations are required to suppress feeding after injection into the perifornical hypothalamus. In contrast, PPA has some anorexic activity within the PVN but not within the perifornical hypothalamus. PMID- 2224546 TI - Characterization of the dynamic nature of microglial cells. AB - Dynamic properties of ramified microglia were investigated in tissue cultures of rat brain cells. Microglia were identified in viable cultures based on previously determined aspects of their morphology and location, and this identification was confirmed through immunohistochemical staining for type-three complement receptors. When living microglial cells were monitored using time-lapse video recording, an extremely dynamic nature was revealed. These cells exhibited morphological alteration, surface and cytoplasmic activity, and migration. All of these properties were both constant and rapid, with individual cells being capable of assuming a completely different overall morphology within a period as short as 5-10 min. These dynamic properties were consistently observed in microglia and appeared specific to this cell type. Thus, ramified microglia appear to possess a unique and highly dynamic nature, and this feature is proposed as a potential marker for these cells. Additionally, the significance of microglial cellular dynamics in the functional role of this cell population in vivo is considered. PMID- 2224547 TI - [Internal medicine at the crossroads]. AB - General internal medicine is falling into subspecialities as the scope presented by individual specialities is no longer manageable. With respect to the patient, however, particularly concerning indications for medication and surgical treatment of polymorbid patients, as well as in solving problems of the aged, general internal medicine is a necessary and expedient branch. The training of specialists in this branch requires the presentation of classified information aimed at diagnosis and therapy. To fulfill the tasks expected of a specialist in internal medicine he has to build up a bank of diagnostic and therapeutic data of high quality. PMID- 2224548 TI - [Perioperative myocardial infarct in association with surgical treatment of coronary heart disease]. AB - Perioperative myocardial infarction is a major complication of revascularization surgery of the heart which can negatively affect both the quality and duration of the patient's life. The aim of the paper is to contribute to the understanding of the problem which involves the definition, incidence, pathogenesis, diagnosis, complications, therapy and prognosis of perioperative myocardial infarction. One of the basic factors implicated in the development of perioperative derangement of the cardiac muscle is closely analyzed, namely insufficient protection of the myocardium with subsequent ischemia-reperfusion induced myocardial damage. Pitfalls of electrocardiographic diagnosis are pointed out and the rather complicated interpretation of increased enzyme levels following cardiac surgery is discussed. Complications, management, as well as early and late prognosis of patients with perioperative myocardial infarction are also dealt with. PMID- 2224550 TI - [Laminotomy and reconstruction of the spinal canal in an experiment]. AB - Surgical access into the spinal canal allowing reconstruction of the axis of the body is reported. The technique of laminotomy was first tested on 5 dogs which were to be involved in other experiments. Healing of the spinal column and overall outcome were followed up on further 4 dogs surviving three months after the procedure. The operation, carried out in general anesthesia induced by IV administration of thiopental (SPOFA), proved to be relatively simple in all the 9 dogs, weighing 10-24 kg. Plain radiologic, perimyelographic, as well as histologic examinations performed in 4 dogs after three-month survival showed virtually perfect healing of the reconstructed spinal canal and no stenosis at the site of the procedure. PMID- 2224549 TI - [Changes in circulating catecholamine levels in old rats under basal conditions and during stress]. AB - The aim of the paper was to study the levels of circulating catecholamines in unrestrained cannulated rats under basal resting conditions and after exposure to two stressors. Catecholamines were determined radioenzymatically in 4-, 11-, 12-, 24-, and 28-month-old rats. Immobilization and exposure to ether vapors were used as stress models. The results confirmed a definite trend to increased norepinephrine (NA) levels, concerning partially also epinephrine (ADR) levels in older animals compared to young ones. During immobilization the plasma NA response was markedly increased in 11-month-old rats, whereas in 28-month-old rats the increase was only mild. Plasma ADR concentration was only slightly elevated in 11-month-old rats, whereas in the older animals no changes were recorded compared to 4-month old rats. On comparing the age groups studied after exposure to ether vapors, the oldest age group of 24-month-old rats showed a slower return of the stress-induced higher plasma NA levels to initial values. On balance, the response of circulating catecholamines depends on the age of the animals and on the stressor used. PMID- 2224551 TI - [Experience with postmortem chromosome analysis]. AB - Over the years 1986-1988 necroptic material, collected according to 5 established indication groups, was cultured. A total of 202 samples of necroptic material cultured and 122 of these samples were analyzed cytogenetically. Seventeen pathologic karyotypes were diagnosed in the material, namely 7 cases of Down's syndrome, 2 cases of Klinefelter's syndrome, 2 cases of D/D translocation, 1 case of Turner's syndrome, 1 case of gonosomal mosaicism, and 1 case of Patau's syndrome. PMID- 2224552 TI - [Systolic and diastolic intervals in patients with hypertrophic obstructive cardiomyopathy before and after withdrawal of verapamil]. AB - Mechanocardiographic investigations were carried out in a group of eight patients with hypertrophic obstructive cardiomyopathy (HOCM) who had been implanted a DDD pacemaker which allowed efficient therapy to be administered in the combination of metoprolol in the dose of 300 mg/day and verapamil in doses of 240-480 mg/day. The investigation was repeated one week after temporary withdrawal of verapamil. The control group consisted of six patients with idiopathic third-degree-complete AV block with implanted DDD pacemakers. Over the period of 24 hours before investigation, these patients received 300 mg of metoprolol. All the patients had the same heart rate (70 bpm) and a constant PQ interval (0.18 s). Statistical analysis of the obtained data revealed the following findings: 1. There was no difference between the control group and the group of HOCM patients treated with verapamil. 2. Withdrawal of verapamil in HOCM patients resulted in a significant prolongation of the 2-0 interval and shortening of the O-c interval recorded on apexcardiogram compared to the control group. In conclusion, verapamil affects LV diastolic parameters in patients with HOCM and the changes are compatible with the beneficial effects of verapamil. These changes may however result partly from increased left atrial pressure due to atrial poisoning with verapamil. PMID- 2224553 TI - [Determination of functional "lipid age" on the basis of analysis of serum fatty acids]. AB - The composition of total fatty acids was analyzed in the serum of subjects with normal lipid and glycide metabolism, aged 20 to 89 years. A mathematico-empirical procedure was applied and on using the method of multiple linear regression the formulas of biological function age, designated as lipid age, were established, with individual serum fatty acids and their ratios in relation to characteristic attributes of markers of aging as independent variable parameters. Further correction of lipid age to the chosen level of 60 years was described and the thus corrected lipid age was expressed in percentages. Application of the obtained formulas of lipid age in the series studied showed that the increase rate of lipid age was higher in men by an average of 5.5% compared to women, which represents a difference of 3.8 years. The obtained results demonstrate a significant relationship of fatty acids to the process of aging and their potential use in evaluating processes affecting lipid metabolism. PMID- 2224554 TI - [Functional status of thrombocytes in men of various age groups]. AB - The functional state of thrombocytes was compared in men of three age groups, i.e. below 46 years, within the range of 46 to 59 years, and above 59 years. Thrombocytes of old people were found to be more sensitive to such aggregation inductors as ADP, collagen, arachidonic acid, and adrenaline compared to thrombocytes of subjects from the younger age groups. A further finding was that blood platelets of old men produced significantly greater amount of ATP than recorded in young men and this may account for hyperactivity of thrombocytes in old age. PMID- 2224555 TI - [Present trends in the treatment of occlusive diseases of the peripheral arteries of the lower extremities]. AB - Occlusive diseases of arteries of the lower extremities with underlying atherosclerosis present a serious medical problem. Despite some generally accepted principles, the diagnostic and therapeutic process in this disease keeps constantly developing. The author deals not only with verified therapeutic procedures such as reconstructive surgery of arteries, endarterectomy, profundoplastics, sympathectomy, but also with the diapeutic method of treatment, percutaneous transluminal angioplasty, which is being used ever more frequently. In indicated cases, percutaneous transluminal angioplasty is considered to be the alternative method to arterial reconstructive surgery. The algorithm of treatment applied in the author's department is presented. PMID- 2224556 TI - [Local complications worsening the results of surgical treatment of colorectal carcinoma in older patients]. AB - The authors compare the results of surgical treatment for colorectal carcinoma in 150 patients aged over 69 years, seen over the years 1979-1988, who had developed local complications requiring urgent surgery. Of gerontologic patients with colorectal carcinoma these represented 24.6%. The cause of the complications was late diagnosis mostly due to the patient's neglect who failed to appreciate an even evident symptomatology. These serious complications of colorectal carcinoma did not present an inoperable condition and in 34% the tumor could be radically removed. The advanced age of the patients along with the necessity of urgent surgery are the major risk factors responsible for the high mortality rate compared to patients who underwent elective surgery. PMID- 2224557 TI - [Phospholipids in the human myometrium in various stages of contraction before and during labor]. AB - A detailed analysis of the myometrium showed that the physical state of phospholipids--fluidity--depends on the ratio of their individual components and changes in relation to the state of contractile activity. The results indicate that before term of labor changes in the fluidity of myometrial phospholipids as well as increased availability of arachidonic acid for prostaglandin synthesis can induce preterm onset of contractile activity. Possibilities of affecting these mechanisms, which belong to the many potential factors inducing preterm labor, are discussed. PMID- 2224558 TI - [The effect of sex hormones on calcium ion transport in the myometrial cells in rabbits]. AB - The effect of estradiol, progesterone, and testosterone on calcium ion transport was studied in the rabbit uterus. To investigate the effect of sex hormones on voltage-dependent calcium channels, the isolated uterus was incubated in Ca2(+) free depolarizing K+ solution. In this solution cumulative dose-response curves to CaCl2 were obtained by increasing the Ca2+ concentration (10(-5)-10(-3) mol.l 1). A decrease of the maximal contractile response to CaCl2 was recorded after in vitro pretreatment with estradiol (1.8 x 10(-5) mol l-1), (6.4 x 10(-1) mol) and testosterone (5.8 x 10(-5) mol.l-1). The pD2 values were unchanged. The possibility of affecting calcium ion release from intracellular stores by sex hormones was observed indirectly on using Ca2(+)-free Tyrode's solution with 0.8 nmol EDTA. Contractile responses of the isolated uterus were induced by single application of norepinephrine (NE) in the dose of 2 x 10(-4) mol.l-1. Pretreatment with sex hormones decreased the contractile responses of the uterus to NE. The obtained results suggest an important involvement of calcium ions in the mechanism of action of sex hormones upon the myometrial smooth muscle. PMID- 2224559 TI - [Foot pain in the elderly]. AB - The paper draws attention to the problem of the aging foot characterized by a complex of degenerative changes and other accompanying diseases--multimorbidity. Affections of the foot rank fourth in the examinations carried out in outpatients. A series of 100 randomly selected patients above the age of 60 who presented with affections of the foot for orthopedic examination was analyzed. In order to establish optimal preventive and therapeutic measures, correlation between foot pain and foot deformity was assessed and the most frequent etiologies of the painful foot and the most frequent localizations of maximal pain in the foot were determined. In relation to pain the author emphasizes the necessity to set up the present functional diagnosis and to apply a complex approach considering not only diseases which conventionally fall under the care of the orthopedist. The latter issue is particularly important in the setting of policlinics with narrow specialties where synthesis of the established findings is sometimes lacking. Frequent affections of the foot encountered in orthopedic practice require a complex analysis of the problem. PMID- 2224560 TI - Endocrine--metabolic crises. PMID- 2224561 TI - Endocrine and metabolic issues in critical care: a practitioner's perspective. PMID- 2224562 TI - Pheochromocytoma. PMID- 2224563 TI - Hypertensive crisis. PMID- 2224564 TI - Disorders of calcium, phosphorus, and magnesium. PMID- 2224565 TI - Serum potassium concentration abnormalities. PMID- 2224566 TI - Thyroid disorders. PMID- 2224567 TI - Anterior pituitary disease. PMID- 2224568 TI - Adrenal disorders. PMID- 2224569 TI - Nursing responsibilities in endocrine emergencies. PMID- 2224570 TI - Serum sodium concentration abnormalities. PMID- 2224572 TI - The urea-soluble low molecular weight cuticle proteins from the different developmental stages of Dacus oleae. AB - The cuticle proteins of the insect Dacus oleae have been isolated by extraction with a solution of 7 M urea. The affinity properties of cuticle proteins, isolated from the third instar larvae (L3DCPs 1-7), to chitin have been studied. Purified cuticle antigens were polymerized by glutaraldehyde and used for raising antibodies. The developmental appearance of the cuticle proteins has been studied by two-dimensional electrophoresis. PMID- 2224571 TI - Endochondral mineralization in cartilage organoid culture. AB - In the development of secondary bone, mineralization of the cartilage matrix is the first step in endochondral mineralization. The circumstances of cartilage mineralization are not known. Influences of the periosteal tissue have been mentioned. In order to investigate the role of osteoblastic cells in endochondral mineralization, cartilage organoid cultures were induced to mineralize by the addition of beta-glycerophosphate (beta-GP). In cartilage organoid culture, embryonic mouse limb bud mesenchymal cells were grown at high-density. The cells differentiated into mature chondrocytes and produced hyaline cartilage matrix. When cartilage had formed after 6 days in vitro, 10 mM beta-GP was added. The developed mineralized cartilage was investigated by morphological means. Seven days after the addition of beta-GP, the first mineralized spots were visible mainly in the internodular, noncartilage tissue. After 12 to 14 days, large areas of cartilage were mineralized, and after 21 days, nearly the whole culture had been mineralized. Electron microscopic investigations showed a dramatic alteration of the cartilage matrix followed by a homogeneous mineralization of the cartilage matrix. The chondrocytes in the mineralized area died and faded. Typical rod-like apatite crystals were visible at the border between the mineralized and the unmineralized matrix. This result closely resembles the in vivo situation of cartilage mineralization. Addition of osteoblastic calvarial cells enhanced the mineralization process, as did the addition of conditioned medium of calvarial cell monolayers. Under these treatments, mineralization started after 3 days and reached a maximum after 14 days. On the other hand, addition of mouse skin fibroblast-like cells without a direct contact to the cartilage inhibited cartilage mineralization. These results indicate that osteoblastic cells induce endochondral mineralization, whereas fibroblast-like cells inhibit this mineralization via soluble factors. PMID- 2224573 TI - Lectin binding beneath the epithelium and in smooth muscle cells in the developing bronchial tree. AB - Components of the subepithelial stratum in developing rat lung reacted transiently with Maclura pomifera agglutinin (MPA) and Aleuria aurantia agglutinin (OFA) conjugated to horseradish peroxidase. These lectins possess selective affinity for and serve to localize glycoconjugates (GCs) with terminal Gal/GalNAc and Fuc, respectively. Staining was strongest with both lectins in the proximal bronchial tree and decreased peripherally to growing buds where it was absent. MPA staining of subepithelial structures decreased from the pseudoglandular through the canalicular period and disappeared by the terminal sac stage. Disappearance of this subepithelial reactivity coincided with appearance of apical MPA-positive glycoconjugate in the canalicular period. OFA stained selectively a layer of flattened cells and a thin extracellular stratum under the epithelium of proximal bronchi in the canalicular period. This lectin affinity extended farther peripherally in the pseudoglandular interval and diminished thereafter. The layer of OFA-positive cells underlying the epithelium was identified immunohistochemically as immature smooth muscle. These muscle cells gained contractile protein while losing surface lectin reactivity during fetal development. The high iron diamine method localized sulfated GC in basement membrane of proximal respiratory passages in the fetal lung. The results attest to the involvement of specific GCs in mediating epithelial-mesenchymal cell interaction during critical stages of bronchial morphogenesis. PMID- 2224574 TI - Immunological evidence for the presence in sea urchin embryos of a cell adhesion protein similar to mouse uvomorulin (E-cadherin). AB - A tryptic fragment (88 kDa), obtained from external digestion of sea urchin embryos carried out in the presence of calcium, shows immunological cross reactivity with polyclonal and monoclonal antibodies (DECMA-1) against mouse teratocarcinoma uvomorulin. Fab fragments obtained from anti-mouse terato carcinoma uvomorulin mono- and polyclonal antibodies, and from polyclonal antibodies against the partially purified 88-kDa tryptic fragment, decompact early sea urchin embryos and block reaggregation of dissociated sea urchin blastula cells. These data indicate the presence of an uvomorulin-like protein in sea urchin embryos and suggest an important role for this protein in embryonic development. PMID- 2224575 TI - A morphological study of primordial germ cells at pregastrular stages in the chick embryo. AB - The spatial distribution, germ layer location, number and appearance of primordial germ cells (PGCs) are studied. Blastoderms from stage X (Eyal-Giladi and Kochav, 1976) to stage 2 (Hamburger and Hamilton, 1951) were serially sectioned and distribution patterns of PGCs were reconstructed. The presence of PGCs in clusters was noted at all stages examined. PGCs were found in relation to the epiblast, the primary hypoblast and in the blastocoel, during the whole period under examination. These observations show that PGCs can be directly studied at blastula stages. The results are consistent with observations on an early segregation of chick germ line that begins as early as stage X. PMID- 2224576 TI - Transdifferentiation of quiescent parenchymatous cells into tracheary elements. PMID- 2224577 TI - The current developments and their implication for the health system in the future. PMID- 2224578 TI - Computers and the future practice of medicine: issues and options. PMID- 2224579 TI - Technology assessment of pharmaceuticals. The necessity of user perspective. PMID- 2224581 TI - Re-organizing primary health care in Finland: from growth to quality. PMID- 2224583 TI - The future of "the peoples' home": development and challenges for the Swedish welfare state in the coming decades. PMID- 2224582 TI - Service management: New Zealand's solution to the problems of quality assurance and financial control. PMID- 2224580 TI - Developments in Dutch health care policy: the ideology of market mechanism. PMID- 2224584 TI - [Probable impact of the policy of health service decentralization in Latin America]. PMID- 2224585 TI - Lessons from health care competition in the United States during the 1980s. PMID- 2224586 TI - The viral etiology of Paget's disease of bone: a new perspective. PMID- 2224587 TI - Health and hormonal characteristics of premenopausal women with lower bone mass. AB - A study of clinical renal and endocrinologic status was undertaken to determine whether the lowest maximal bone mass observed in premenopausal women, aged 20-40 years, was a result of undiagnosed disease or represented a continuum of measurement in young adult women. A clinical sample (n = 53) was generated from an epidemiologic cross-sectional study (n = 535) designed to characterized correlates of maximal bone mass. Cases were 28 premenopausal women whose femoral bone mass as in the lowest 5th percentile of the distribution, less than 0.75 g/cm2 at the femoral neck. Controls were 25 randomly selected premenopausal women whose femoral bone mass was within 1 SD of the mean of the femoral bone mass distribution. There was no indication of increased frequency of disease among the cases as compared with the controls. No occult hypogonadism, thyrotoxicosis, hyperparathyroidism, myeloma, or renal insufficiency was observed to explain lower bone mass measurement. However, cases had significantly lower estradiol levels (75 versus 106 pg/ml, P less than 0.05) and higher luteinizing hormone levels (3.8 versus 3.1 mIU/ml, P less than 0.07) than controls. Though preliminary, these findings suggest that lower estradiol levels may contribute to significant differences in bone mass even among healthy women at the time of maximal bone accumulation. PMID- 2224588 TI - Human pharmacokinetics of orally administered strontium. AB - Pharmacokinetics of orally administered SrCl2 (2.5 mmol) were studied in six healthy male volunteers. In the overall plasma concentration time (C-t) curves, two absorption phases were observed due to two dominant intestinal absorption loci. A method was devised to obtain separately the plasma C-t curves associated with each of the two absorption loci (curve 1 and curve 2). These curves and the overall plasma C-t curve were analyzed with a nonlinear estimation program (PCNONLIN). Pharmacokinetic parameters (mean +/- SD, n = 6) calculated from the overall curve were as follows: peak plasma concentration (Cmax) 3.55 +/- 1.22 micrograms/ml and area under the plasma C-t curve (AUC affinity) 9138 +/- 1930 micrograms.min/ml. The pharmacokinetic parameters calculated from curve 1 were as follows: terminal plasma elimination half-life time 47.3 +/- 7.9 hour, the plasma elimination half-life time of the preceding phase 5.2 +/- 3.3 hour, Cmax 1 3.09 +/- 0.95 micrograms/ml, the first-order absorption rate constant for absorption locus 1 (Ka,1) 5.7 +/- 1.2 * 10(-2) minute-1 and the time lag (tlag,1) 11.7 +/- 7.9 minute. In three of the subjects the pharmacokinetic parameters of absorption locus 2 could be evaluated: Ka,2 = 4.6 +/- 0.4 * 10(-2) minute-1, tlag,2 = 77.3 +/- 4.0 minute, tmax,2 = 153 +/- 16 minute, Cmax,2 = 0.9 +/- 0.4 micrograms/ml and AUC 2 affinity = 1204 +/- 565 micrograms. minute/ml. and AUC2 affinity = 0.14, indicating that 14% of the absorbed dose was absorbed via the second locus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224589 TI - Effects of tumor necrosis factor alpha on proliferation and expression of differentiated phenotypes in rabbit costal chondrocytes in culture. AB - Tumor necrosis factor alpha (TNF alpha) decreased the synthesis of glycosaminoglycan (GAG) in rabbit costal chondrocytes in culture, but did not stimulate the release of GAG from cell layers. Like chondrocytes cultured in control medium, chondrocytes cultured in the presence of TNF alpha produced putative "cartilage-specific" proteoglycans identified by density gradient centrifugation under dissociative conditions. Although TNF alpha decreased the synthesis of the proteoglycans, it did not change their monomeric size, which is a marker of cartilage phenotypes. Moreover, TNF alpha did not affect the responsiveness to parathyroid hormone, insulin-like growth factor I, or transforming growth factor beta, which is known to stimulate GAG synthesis in cultured chondrocytes. TNF alpha decreased the alkaline phosphatase activity in the chondrocytes dose dependently. On the other hand, it stimulated their DNA synthesis slightly, but significantly. The stimulatory effect of TNF alpha on DNA synthesis was potentiated by fibroblast growth factor, epidermal growth factor, and fetal bovine serum. These findings suggest that in the presence of hormones and growth factors, TNF alpha promotes the proliferation of chondrocytes while suppressing their further differentiation at the stage of synthesis of cartilage specific proteoglycans. PMID- 2224590 TI - 1,25 Dihydroxyvitamin D3 modifies cyclosporine-induced bone loss. AB - We have previously shown that cyclosporin A (CsA) produces high bone remodeling with resorption exceeding formation and loss of bone volume in the rat. This may have important clinical implications where CsA is widely used in organ transplantation. 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is a bone mineralizing hormone which also has immune modifying properties. Consequently, we studied the effect of combined CsA and 1,25(OH)2D3 administration over 28 days in four groups of rats. Group A received vehicle (n = 10), group B CsA (15 mg/kg) (n = 10) alone, group C 1,25(OH)2D3 plus CsA (n = 15), and group D 1,25(OH)2D3 alone (20 ng/100 g) (n = 15). Rats were bled periodically at day 0, 7, 14, and 28 and Ca, parathyroid hormone (PTH), 1,25(OH)2D, osteocalcin (bone Gla-protein, BGP), BUN, and creatinine were measured. Rats were sacrificed on day 28 and bones were examined histomorphometrically. Compared to controls, CsA resulted in significant elevation of BGP and a transient increase in 1,25(OH)2D with excess bone remodeling and loss of bone volume. 1,25(OH)2D3 administration produced hypercalcemia, a significant rise in BGP, with suppression of PTH and increased osteoid volume. Combined therapy prevented the loss of bone volume probably due to increased osteoid tissue and enhanced osteoblast activity. Renal dysfunction, a side-affect of CsA, was not a factor. In conclusion, 1,25(OH)2D3 combined with CsA restores bone volume which is accompanied by increases in serum calcium and BGP. PMID- 2224591 TI - A model for investigating the local action of bone-acting agents in vivo: effects of hPTH(1-34) on the secondary spongiosa in the rat. AB - Cytokines and other local factors are likely to play an important role in bone remodeling. The purpose of this study was to develop an experimental model for evaluating the local action of various hormones and other agents on rat femur trabecular bone in vivo. Through a 1 mm diameter hole (1 mm deep) on the lateral aspect of the distal cortex of a rat femur (0.9 cm above the joint), a polyethylene tube was inserted and glued onto the bone. This tube was connected to a vascular-access-port which was implanted subcutaneously in the hip area of male Sprague-Dawley rats weighing 190-210 g. To evaluate this model, a single 50 microliters injection of 10(-8), 10(-10), or 10(-12) M hPTH(1-34) was given 1 day after catheter implantation and the number of osteoclasts was estimated 30 hours later. Bones were fixed, embedded, and stained with Masson's Trichrome stain and subjected to histomorphometric analysis. The single local parathyroid hormone (PTH) injection caused a dose-dependent increase in osteoclast number from 1.7 +/ 0.3 for phosphate-buffered saline (PBS) controls to 3.4 +/- 0.5, 5.8 +/- 0.9, and 5.4 +/- 1.0/mm for 10(-12), 10(-10), and 10(-8) M PTH, respectively. There was no increase in osteoclast number in the femurs of PBS-injected control rats, in the femurs of sham-operated rats, or in the untreated contralateral femur of the PTH-injected rat. The local injection of hPTH(1-34) did not change serum calcium, serum phosphate, or the urinary phosphate/creatinine ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224592 TI - Effects of vitamin D-binding protein on bone resorption stimulated by 1,25 dihydroxyvitamin D3. AB - Vitamin D and its metabolites are tightly bound to the serum vitamin D-binding protein (DBP) and only the free hormone is considered to be physiologically active. On the other hand, DBP could interact with cell membranes and even favor its intracellular entry. The present study was undertaken to examine the effects of DBP on bone resorption stimulated by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Forelimb bones from 19-day-old fetal rats were cultured for 5 days in the presence of purified human or rat serum albumin (hSAP or rSAP) and 1,25(OH)2D3, with or without human or rat DBP (hDBP or rDBP). Bone resorption was assessed by measuring the release of previously incorporated 45Ca. We found that the resorptive response to 1,25(OH)2D3 was minimally altered by hDBP (5 microM). The minimal effects of hDBP on 1,25(OH)2D3 activity on rat bones might be explained by a 6-fold lower affinity of hDBP (1.1 x 10(7) M-1) than rDBP (5.9 x 10(7) M-1) for 1,25(OH)2D3 or by species differences in cellular recognition of DBP. In a homologous rat system, however, rDBP at low (0.5 microM) or physiological (5 microM) concentration significantly decreased 1,25(OH)2D3-induced bone resorption. These data therefore support the hypothesis that free rather than DBP bound 1,25(OH)2D3 is physiologically important. PMID- 2224595 TI - Eagles and turkeys. PMID- 2224593 TI - The effect of swimming on bone modeling and composition in young adult rats. AB - The purpose of this study was to investigate the adaptability of long bones of young adult rats to the stress of chronic aquatic exercise. Twenty-eight female Sabra rats (12 weeks old) were randomly assigned to two groups and treatments: exercise (14 rats) and sedentary control (14 rats) matched for age and weight. Exercised animals were trained to swim in a water bath (35 degrees +/- 1 degree C, 1 hour daily 5 times a week) for 12 weeks loaded with lead weights on their tails (2% of their body weight) (BW). At the end of the training period following blood sampling for alkaline phosphatase, all rats were sacrificed and the humeri and tibiae bones were removed for the following measurements: bone morphometry, bone water compartmentalization, bone density (BD), bone mineral content (BMC), and bone ions content (Ca, Pi, Mg, Zn). The results indicate that exercise did not significantly affect the animals' body weight, bone volume, or length and diameters. However, bone hydration properties, BD, bone mass, and mineralization revealed significant differences between swim-trained rats and controls (P less than 0.05). Longitudinal (R1) measurement was higher by 43% for both humerus and tibia, and Transverse (R2) relaxation rates of hydrogen proton were higher by 117 and 76% for humerus and tibia, respectively; fraction of bound water was higher by 36 and 46% for humerus and tibia, respectively. BD, bone weight, and ash were higher by 13%. BMC and bone ions content were higher by 10%, and alkaline phosphatase was higher by 67%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224596 TI - An interview with Gilles Dube, CDA President. Interview by P. Ralph Crawford. PMID- 2224594 TI - Radiation-sterilized insoluble collagenous bone matrix is a functional carrier of osteogenin for bone induction. AB - The influence of gamma radiation on the role of the collagenous substratum as a carrier for proteins which cause bone induction was examined. Osteoinductive demineralized bone matrix was extracted by 4 M guanidinium hydrochloride. The insoluble collagenous bone matrix (ICBM) obtained was not osteoinductive; however, when reconstituted with partially purified osteogenin, bone induction was restored. In order to apply the principle of bone induction to clinical use, methods of sterilization must be optimized to maintain the osteoinductive activity of bone allografts. The inactive substratum was irradiated and reconstituted with an active, partially purified bone extract and bioassayed. Irradiation of the ICBM by a Cobalt 60 source at a dose of 1 and 3 Mrads had no deleterious effect on the functional role of the substratum. PMID- 2224597 TI - 'Scholarly case report'. PMID- 2224598 TI - Unusual dental calculus. PMID- 2224599 TI - What dental phobics say about their dental experiences. AB - Previous surveys have indicated that there is a substantial proportion of dentally anxious individuals in the general population. Many of these individuals avoid contact with dentistry as much as possible, while fearful individuals who present themselves for treatment are probably too uncomfortable or too afraid to make their views known. Consequently, a study of the feelings and attitudes of a group of dental phobics was carried out as part of a larger study of the efficacy of psychological treatments for excessive dental anxiety. The subjects were recruited by means of a newspaper advertisement and asked to complete a questionnaire designed to obtain information regarding their dental experiences and attitudes. Twenty-three individuals provided enough data for analysis. They were distributed widely in terms of age, education, income levels, and general fearfulness. They reported less satisfaction with the level of understanding or acceptance found in the last dentist they had seen than with the dentist's level of technical competence and the diagnostic information they received. Dental phobics who had been to a dentist in the past year were generally more satisfied with their dentist than those who had not. It is suggested that a good dentist patient relationship based on understanding and acceptance is an important factor in overcoming the avoidance of fearful patients. PMID- 2224600 TI - [Oral manifestations of skin diseases]. AB - There exists a multitude of systemic diseases which exhibit consequential oral manifestations. Dermatologic disorders frequently involve intraoral and perioral tissues which dental practitioners should be familiar with. A compilation of disorders including; bullous diseases (such as Pemphigus Vulgaris, Erythema Multiforme, Pemphigoid, Dermatitis Herpetiformis, Epidermolysis Bullosa, and Darier's disease), as well as non bullous diseases (such as Lichen Planus, Psoriasis, Lupus erythematosus, Scleroderma, and Perioral Dermatitis); and their oral manifestations are presented in order to facilitate their early diagnosis and subsequent treatment. PMID- 2224601 TI - Optimal placement of osseointegrated implants. AB - In summary, there is no substitute for thorough diagnosis, treatment planning, and meticulous surgical and prosthetic treatment. Proper utilization of surgical and radiographic correction-stents is one of the important aspects of the presurgical phase. The stents facilitate the accurate placement of implants in optimal positions where sufficient bone is present. In cases with insufficient bone, the stents may help in making a strategic alteration of the chosen implant site. PMID- 2224602 TI - The City of Toronto's geriatric dental program. AB - The past four years have witnessed the development of a comprehensive dental program for the seniors of the City of Toronto. This program is based upon the principles of dental health promotion and prevention. It recognizes the distinct needs of seniors who are institutionalized. It also addresses the needs of those low-income seniors living in the community. The overall result is an integrated program aimed at improving the dental health of all seniors in Toronto. PMID- 2224604 TI - [Subcutaneous sarcoidosis--a case report]. AB - A 35 year-old female patient suffered from several brownishred nodule-plaques over both legs and left knee for two months. General malaise and exertional dyspnea were also noted. Skin biopsy shows multiple epithelioid cell tubercles with asteroid body in multinucleated giant cell located in the deep dermis and subcutis. No fungus, mycobacterium or foreign body could be found by special stains. Chest X-ray reveals bilateral hilar lymphadenopathy. She had neither sensory impairment nor DM history. Based on the above findings, we believed that she is a victim of subcutaneous sarcoidosis. PMID- 2224603 TI - [Evaluation of compensator used in radiation therapy]. AB - A radiation beam incident on an irregular or sloping surface produces skewing of isodose curves and may give rise to unacceptable nonuniformity of the dose distribution within the target volume or cause excessive irradiation of sensitive tissues. The concept of using a compensator, first introduced by Ellis, to circumvent the skewness of isodose curves was elegant. Other workers followed suit elaborating further and extending the procedures. The treatment of chest wall tumors is of special interest and compensators were frequently used in their management. The compensators of aluminum and copper were systematically examined for 6 and 10 MV X-rays. Compensating thickness ratios was determined from equivalent dose measurement at compensating depth by placing compensator at the regular blocking tray for maintaining the skin sparing feature of high energy photon beams. The compensator must compensate not only for the reduction of the primary beam attenuation due to tissue deficit, but also for the loss of scattering by the missing tissues. It was found that the compensating thickness ratios (CTR) was not a constant value and was dependent on the tissue deficit, field size, compensating depth and the material of compensator, but was independent of the energy. As the tissue deficit is increased, the CTR decreases, since the loss of scattering for the deficit volume can be compensated by the lowered attenuation of the compensator. As the field size is increased, the CTR decreases. From the study of central axis depth dose for various deficit thickness, normalized at the median plane of no tissue deficit, it was found that compensator can compensate the dose accurately to one depth only and the compensation to other depth is approximate, and that the compensating error is increased with greater tissue deficit and further depth. The effectiveness of the compensating system with a stair-step polystyrene phantom representative of varying tissue deficits over a small treatment field (20 cm x 20 cm) was also studied with film dosimetry and the error was within 3%. The compensator thickness ratios must be measured in different radiation beams from different treatment machines and in different irradiation conditions because there are major difference between the CTR data obtained directly from experiments and the data besed on calculation from attenuation coefficient mu, physical density rho or electronic density, rho e. The specific CTR reported for aluminum and copper in the literature should only be used as a guideline. PMID- 2224605 TI - [Growth catch-up in the case of congenital hypothyroidism after delayed treatment -a case report]. AB - We report a case of congenital hypothyroidism, presenting with growth and mental retardation since childhood, but in which the diagnosis was not made until he was 17 years old. Because of such an unusually long delay in treatment, we focussed on the growth catch-up. This included the change of skeletal growth, puberty and mentality after a 4-year treatment period. He was 114 cm in height (height age 5.5 years) with the upper segment measuring 60 cm and lower segment 54 cm (U/L ratio 1.1). His bone age was that of a six year old and he had no secondary sexual characteristics. IQ testing showed a full scale IQ of 68, verbal IQ 74 and performance IQ 64. After 4 years of treatment, his height caught up to 152 cm (height age 12.5 years), with the upper segment 77.2 cm, and that of lower segment 74.8 cm (U/L ratio 1.03). The bone age had advanced to that of a 17 year old. His pubic hair emerged after 18 months of therapy (at a chronologic age of 18.5 years), accompanied by a normalization of testosterone and a normal response to a GnRH test. His IQ test was rechecked after 2 years of treatment. His full scale IQ was 78, verbal IQ 77 and performance IQ 83. In the mean time, the patient got a job being more alert, active and self-confident following his growth catch-up. PMID- 2224606 TI - Insulin autoimmune syndrome as a cause of hypoglycemia--report of four cases. AB - Insulin autoimmune syndrome is a syndrome consisting of fasting hypoglycemia, hyperinsulinemia and detectable insulin-binding antibodies in patients who have never been exposed to exogenous insulin. Four cases who developed symptoms of hypoglycemic attack with self-limited duration and spontaneous remission were collected in our hospital from 1984 to 1988. The elevated serum total and free insulin and C-peptide levels, as well as the titer of insulin autoantibodies, decreased gradually; but insulin autoantibodies were still present in the serum for more than six months after the initial episodes of hypoglycemia. Three of four patients had Graves' disease and developed the syndrome after methimazole treatment. The fourth one had a history of hemorrhagic cystitis and denied history of specific drug exposure. The cause or stimulus for insulin autoantibody formation is still unknown, but drugs containing a sulfhydryl group like methimazole may play a role in the development of the syndrome. Extremely high insulin antibodies in patients with fasting hypoglycemia along with elevated serum levels of insulin and C-peptide suggest a diagnosis of insulin autoimmune syndrome and usually exclude the possibility of insulinoma or factitious hypoglycemia. PMID- 2224607 TI - Goodpasture's syndrome--a case report. AB - Goodpasture's syndrome is a disease characterized by diffuse pulmonary hemorrhage and glomerulonephritis with circulating anti-glomerular basement membrane antibody (anti-GBM antibody). Although it is reported in the western world, it is rarely diagnosed in Taiwan. We report a 26-year-old male admitted due to pulmonary hemorrhage and rapid progressive glomerulonephritis. Renal biopsy showed diffuse glomerular proliferation and 90% crescent formation, and immunofluorescence stain showed diffuse linear staining of IgG, C3, IgA, IgM along glomerular basement membranes and tubular basement membranes. He was treated with immunosuppressive agents. Pulmonary hemorrhage improved rapidly, but his renal function was severely impaired and he remained dialysis dependent. PMID- 2224609 TI - [Gastric volvulus in childhood--report of two cases]. AB - Gastric volvulus is a rare acute abdominal condition, especially in the pediatric field. We reported 2 cases of gastric volvulus presenting with acute abdominal pain, abdominal distension and vomiting. Both were found to be mesentero-axial type gastric volvulus on operation; one was associated with gastrosplenic and gastrocolic ligment laxacity, the other with left side diaphragmatic hernia. Both of them recovered uneventfully with no evidence of recurrence on follow up. PMID- 2224608 TI - [Perinatal listeriosis--a case report]. AB - Listeria monocytogenes, an uncommon perinatal infection in human, has been reported to be correlated with abortion, premature labor, intrauterine fetal sepsis, intrauterine fetal death and neonatal infections. Reported here was the first case of perinatal listeriosis complicated with Listeria monocytogenes chorioamnionitis at 33 weeks' gestation in Taiwan. The transabdominal amniocentesis in this particular case confirmed the diagnosis. An live premature male fetus was delivered by emergency cesarean section on the next day of hospitalization due to acute fetal distress. The acute ill baby developed signs of meningitis on the following day. Blood culture of Listeriosis monocytogenes indicated early onset neonatal listeriosis. Brain sonography showed hydrocephalus after a one-month period antibiotic treatment, he was lost to follow-up one month later. A review of the literature is presented to describe the clinical, epidemiological and pathological findings and to highlight their variable presentations and procedures for management. Thus it is of great importance for obstetricians to include listeriosis as a differential diagnosis in cases of fever of unknown origin during pregnancy. Promptly obtaining proper cultures and instituting appropriate antibiotics therapy is emphasized. PMID- 2224610 TI - Post-traumatic fat embolism syndrome--a 10 year retrospective study in Chang Gung Memorial Hospital. AB - Forty patients with post-traumatic fat embolism syndrome (FES) from January 1977 through December 1986 were retrospectively analyzed. Diagnosis was made according to the criteria modified by Guard. All 40 patients had at least two major criteria, namely change in consciousness and hypoxia. Twenty patients (50%) presented with full-blown clinical features. Prompt respiratory support with oxygen mask or nasal prongs was the first line of treatment. Forty per cent of patients responded well, whereas the others had to be advanced to endotracheal intubation and mechanical ventilation with positive end expiratory pressure. Steroids were given to 80% of patients and better results were achieved than in the group not treated with steroids. The mortality rate was low (2.5%) and only four patients suffered prolonged cerebral sequelae. The clinical course and prognosis cannot be predicted from the severity of the fracture. PMID- 2224611 TI - Safety and efficacy of 2% topical minoxidil in the management of male pattern baldness in Chinese. AB - Topic 2% minoxidil solution has been proved to be effective for hair regrowth in 30-40% of male pattern baldness in the United States and Europe. There was no report concerning topical minoxidil in Chinese patients, therefore, we selected 40 patients to investigate the efficacy and safety from December 1988 to January 1989. Those selected patients were consistent with male pattern baldness without systemic disease, and had never used topical hair regrowth agents. Patients applied topical medication 1 ml twice daily and were examined at 1 month intervals. Thirty two patients completed 6 to 12 months (average 9.6 months) of the study, moderate hair growth was found in 22% while minimal growth in 59% of the studied patients. All patients noted their shedding decrease after the application of drugs for 1 to 3 months. Scalp dryness and mild scaling appeared in 2 patients, but were tolerable. Before and after the trial, all patients had a chest roentgenogram, EKG, complete blood counts, urinalysis and blood chemistry studies, and no apparent abnormality was found. The efficacy of 2% minoxidil solution application in our study was less than that in the United States. which might be because some patients did not follow the application order regularly and a more strict evaluation standard was adopted in our series. However, the safety of no systemic adverse effect and the potential of inhibiting progressive shedding of hair were valuable as a topical drug. PMID- 2224612 TI - Atherosclerosis and the lung. PMID- 2224613 TI - Malignant primary cardiac tumour presenting as superior vena cava obstruction syndrome. AB - A 71-year-old male with a malignant primary cardiac lymphoma nearly filling the right atrium presented with symptoms of obstruction of the tricuspid valve and inflow to the right atrium. The tumour was resected as fully as possible; however, a portion of the tumour that had invaded the inferior aspect of the right atrium and the atrioventricular groove could not be excised. Eighteen months after initial presentation, the patient is well and the tumour has not recurred. This is the first case of symptom-free survival of primary cardiac lymphoma for as long as 18 months. PMID- 2224614 TI - Right atrial myxoma with cyanosis due to right-to-left shunting. AB - Primary cardiac tumours are uncommon entities, and myxoma is the most common, comprising about 50% of all these neoplasms. A case of a 43-year-old woman with right atrial myxoma and a shunt through a patent foramen ovale producing severe cyanosis is reported. PMID- 2224615 TI - Near fatal angioedema associated with captopril. AB - Two markedly hypertensive patients in their 70s both had been on captopril for months when they each developed life threatening angioedema. Their families and physicians responded promptly and effectively in saving their lives with one patient receiving tracheotomy and the other 24 h of intensive care with adrenaline, hydrocortisone and antihistamines. Angiotensin converting enzyme inhibitors are not without their significant risks and should not be used when less dangerous but equally efficacious medication is available. PMID- 2224617 TI - The role of coronary angioplasty in patients with associated noncardiac medical and surgical conditions. AB - Percutaneous transluminal coronary angioplasty was performed in 22 patients with associated significant medical or surgical conditions. It was successful in 22 patients. Two had procedure-related complications: one femoral hematoma and one small myocardial infarction. The patients were divided into a 'medical' group (12 patients) and a 'surgical' group (10 patients). In the medical group, mean coronary artery stenosis decreased from 87 +/- 5% to 20 +/- 13% and mean coronary artery stenosis decreased from 57 +/- 2% to 16 +/- 7%. In the surgical group coronary artery stenosis decreased from 83 +/- 9% to 18 +/- 9% and the gradient from 49 +/- 16 to 16 +/- 6 mmHg. Percutaneous transluminal coronary angioplasty allowed the safe management of underlying conditions in all patients so that medical treatment could be continued and noncardiac surgery performed. PMID- 2224616 TI - First coronary heart disease event rates in relation to major risk factors: Quebec cardiovascular study. AB - The incidence of first coronary heart disease (CHD) events was evaluated prospectively in relation to the baseline measurements of systolic and diastolic blood pressure, serum cholesterol, smoking status and education in a cohort of 4576 Quebec men aged 35 to 64 and free from CHD at entry in 1974. From 1974 to 1986, 603 first CHD events were documented. The most frequent first manifestation was angina (6.7/1000 person-years) followed by nonfatal myocardial infarction (4.7/1000) and CHD death 2.2/1000). There was a positive relationship between the first CHD event and systolic (Z = 4.67) and diastolic (Z = 6.50) blood pressure. This relation was observed for angina, nonfatal myocardial infarction and CHD death. Serum cholesterol was also related to all events (Z = 4.99) but more specifically to angina and nonfatal myocardial infarction. Cigarette smoking was significantly related to first CHD manifestations. This relationship for specific CHD events was observed in men who smoked more than 20 cigarettes per day. Men who discontinued smoking one year before the study had a risk not different from those who never smoked. No relationship was observed between years of schooling and CHD events. Blood pressure, cholesterol and smoking constituted nearly two thirds of the attributable risk of first CHD events. PMID- 2224618 TI - Altered antioxidant status in ischemic/reperfused rabbit myocardium: reperfusion time-course study. AB - A progressive impairment in antioxidant status of rabbit hearts was observed when a fixed period (40 mins) of ischemia produced by coronary artery ligation was followed by increasing periods of reperfusion. This was reflected in a reduction in myocardial glutathione levels and an increase in glutathione depletion and production of thiobarbituric acid-reactive substances following in vitro oxidative challenge with t-butylhydroperoxide. Correlation analysis, in which activities of antioxidant enzymes were viewed in relation to biochemical indices of antioxidant status, indicated the functionally relevant suppression of Cu,Zn superoxide dismutase and glutathione reductase activities in ischemic/reperfused tissues. These results and the demonstration of significant decreases in the activity of glutathione-dependent antioxidant enzymes under acidotic conditions suggest that transient impairment in the functioning of antioxidant enzymes may be involved in the triggering of irreversible myocardial ischemia-reperfusion injury. PMID- 2224619 TI - An overview of noninvasive methods of deep vein thrombosis detection. PMID- 2224620 TI - Degenerative lumbar spine disorders in gradient refocused echo axial magnetic resonance images. AB - The axial images of 58 lumbar disks having degenerative disorders imaged by gradient refocused echo (GRE) and spin echo (SE) magnetic resonance imaging (MRI) pulse sequences at high field strength were compared for diagnostic quality. The vacuum phenomenon, calcified disk, and bony hypertrophic changes were better demonstrated by GRE images than by SE images due to magnetic susceptibility effect. Axial GRE images are therefore useful adjuncts to SE images for effective MRI of degenerative lumbar spine disorders at high field strength. PMID- 2224621 TI - MR imaging in hypertrophic neuropathy: a case of hereditary motor and sensory neuropathy, type I (Charcot-Marie-Tooth). AB - We describe findings of Charcot-Marie-Tooth disease in magnetic resonance imaging (MRI). The MRI examination of the lumbar spine with and without gadolinium DTPA showed diffusely enlarged cauda equina, nerve roots, and ganglia. In the setting of appropriate family history and clinical presentation, the findings of diffusely enlarged nerve roots support the diagnosis of hereditary motor and sensory neuropathy, Type I (HMSN I, Charcot-Marie-Tooth). PMID- 2224622 TI - Computed tomography of retroperitoneal perforation after barium enema. AB - A case of retroperitoneal perforation of the rectum complicating a single contrast barium enema is presented. The appearances on computed tomography (CT) allowed accurate depiction of the extent of barium extravasation not appreciated on plain films. Although this is an unusual complication of the barium enema, CT may prove useful when the suspicion of perforation arises. PMID- 2224623 TI - Fibrous dysplasia: magnetic resonance imaging appearance at 1.5 tesla. AB - Fibrous dysplasia has been described in a small number of cases in the literature as showing low signal intensity on T1- and T2-weighted magnetic resonance images. We reviewed magnetic resonance scans of 13 patients with fibrous dysplasia to determine if there might be a characteristic appearance. All lesions had sharply defined borders and were of intermediate signal intensity on T1-weighted images. With T2 weighting, six lesions (46%) showed high signal intensity, four (31%) showed persistent intermediate signal intensity, and three (23%) showed mixed intermediate and high signal intensity. Ten lesions (77%) had inhomogeneous signal intensity and three (23%) had homogeneous signal intensity. We concluded that fibrous dysplasia does not have a characteristic appearance on magnetic resonance imaging. However, magnetic resonance may be helpful in establishing the diagnosis of fibrous dysplasia if low to intermediate signal intensity is seen on both T1- and T2-weighted images. This situation occurred in 54% of our cases, whereas the other 46% had nonspecific signal characteristics indistinguishable from many other bone lesions. PMID- 2224624 TI - Prospective comparison of computed tomography and duplex sonography in the evaluation of recently inserted Kimray-Greenfield filters into the inferior vena cava. AB - A prospective comparison of contrast-enhanced computed tomography (CT) and duplex sonography (DS) was performed to examine the Kimray-Greenfield filter in the inferior vena cava (IVC) in the immediate postoperative period. Fourteen patients were studied for five complications: IVC thrombosis, malpositioning, pericaval hematoma, filter angulation, and prong perforation. Our results found CT to be more efficacious because it was a) able to evaluate more patients with fewer technically inadequate scans and b) more definitive in all categories. However, when visualized, DS was as accurate as CT in the evaluation of thrombosis. PMID- 2224625 TI - Opacification of ascitic fluid on delayed contrast computed tomography scans. AB - Ascitic fluid opacification on delayed intravenous contrast computed tomography scans was observed in eight consecutive patients imaged. This apparently common phenomenon may alter both the sensitivity and the specificity of ascitic fluid detection. It may also serve as a diagnostic aid by making nonascitic intra abdominal fluid collections (ie, pseudocyst and cystic tumor) more apparent. PMID- 2224626 TI - Intra-aortic counterpulsation balloon pumps: CT appearance. AB - Intra-aortic counterpulsation balloon pumps (ICBP) used in the setting of cardiogenic shock or high risk cardiac surgery, have been identified on chest films in the inflated state during diastole (1). We report characteristic computed tomography (CT) findings of an inflated ICBP, discuss its radiographically identified complications, and suggest that the presence of this device should be excluded before suspecting other etiologies for intra-aortic gas. PMID- 2224627 TI - Computed tomography of ruptured aneurysm of the profunda femoris artery. PMID- 2224628 TI - Renal oncocytoma: report of a case with bilateral multifocal oncocytomas. AB - Renal oncocytomas are uncommon, benign tumors that classically are treated by local excision or heminephrectomy. Preoperative differentiation from renal cell carcinoma is invaluable in the planning of treatment. Cases of renal oncocytoma treated conservatively have been reported. This is a case report of bilateral multifocal renal oncocytomas of which only three previous cases have been reported. Diagnosis was made from multiple fine needle biopsies and present treatment consists only of conservative observation. PMID- 2224629 TI - Nonmucosal predominantly serosal eosinophilic enteritis. A case report. AB - A unique case of eosinophilic enteritis with predominant serosal involvement and mucosal sparing, ascites and abdominal adenopathy is reported with computed tomography (CT) and barium study correlation. The clinical presentation may mimic lymphoma or granulomatous disease, (e.g. tuberculosis) but peripheral eosinophilia is a strong differentiating point. PMID- 2224631 TI - Intradural spinal arachnoid cyst. Case report. AB - An intradural spinal arachnoid cyst presenting with spinal cord compression is discussed. This case illustrates the value of magnetic resonance imaging in the diagnosis and follow-up of intradural spinal arachnoid cysts. PMID- 2224630 TI - Right perirenal space. Computed tomography evidence of communication between the bare area of the liver. AB - Computed tomography (CT) images from one cadaver and 11 patients with perirenal fluid collection were reviewed to study whether the right perirenal space communicates with the bare area of the liver. CT of a cadaver obtained after meticulous right perirenal injection of contrast media showed that contrast media extended superiorly into the bare area of the liver. CT of 11 patients with right perirenal hemorrhage or infection showed that fluid collection within the right perirenal space continued upward, crossing the coronary ligament, extending into the bare area of the liver. The inferior vena cava were completely or partially surrounded by fluid. CT of two patients with bleeding hepatocellular carcinoma showed that blood in the bare area continued extending downward into the perirenal space. We conclude that the right perirenal space is open toward the bare area of the liver and fluid collection within one space may communicate with the other space across the coronary ligament. PMID- 2224633 TI - A 58-year-old Vietnamese woman with a 1-month history of an enlarging right infraclavicular mass. PMID- 2224632 TI - Unusual computed tomography findings in hepatic amyloidosis. AB - An unusual pattern of delayed enhancement in a patient with a focal hepatic defect due to amyloidosis is presented. Without the aid of region-of-interest density measurements, the lesion was not appreciated on unenhanced computed tomography scans. PMID- 2224634 TI - Decision support and outcomes of nurses' care planning. AB - One hundred forty-three nurses served as their own controls in planning care for hypothetical patients under three different manipulated conditions of decision support: (A) use of traditional resources; (B) use of a printout of a computerized protocol for care planning (NPC); and (C) use of an NPC protocol and a self study guide. A series of 3 x 5 repeated measures analyses of variance (ANOVAs) were used to evaluate the main effects and interactions of the experimental treatment conditions and the two nurse attribute variables of education and experience (each with five levels). The case problems and conditions were counterbalanced to control for extraneous variables. The repeated measures ANOVA demonstrated significantly higher mean ratings of quality for care planned under both computerized decision support conditions than the traditional condition on all three patient problem situations F(2, 270) = 7.9, p less than .01. Time on task was also significant F(2, 272) = 5.8, p less than .01 with use of the decision support consultants tending to increase time in planning. PMID- 2224635 TI - Creative use of microcomputer software by graduate nursing students. AB - Educating nurses to use computer technology involves complex strategies. As adult students, many are eager to learn uses of computers for nursing education, nursing research, nursing practice, and nursing administration. It is the role of the faculty member to make the computer laboratory experiences meaningful and pragmatic for these 'first time' computer users. This article describes a method that promotes learning by requiring students to solve a nursing problem relevant to their practice using available microcomputer software. PMID- 2224636 TI - RN education flexibility utilizing laptop computers. AB - In a geographic region that is largely rural, baccalaureate faculty teaching RNs needed a program of study that provided flexibility. This article describes a project that incorporates CAI and PCs into RN education. Difficulties and successes of the project are also discussed. PMID- 2224637 TI - The CAREPLAN knowledge base. A prototype expert system for postpartum nursing care. AB - With the growth of scientific knowledge in the health care disciplines, it has become increasingly difficult for practicing health care professionals to store and manipulate the information required to make clinical decisions. Where the decision making process can be defined and validated, expert systems will be able to assist beginning professionals to learn appropriate patterns of decision making. This article discusses the rationale for utilization of expert systems in a nursing environment. A prototype expert system called CAREPLAN, developed for use in an obstetrical environment, was built using Personal Consultant Plus, a software tool based on the LISP language. The project demonstrates that it is feasible to develop and validate an expert system for a specialized clinical environment in a relatively short period of time in comparison to traditional development methods. Graphics were used to enhance textual information and to increase user appeal. Strategies for future implementation and evaluation are outlined. PMID- 2224638 TI - A historical perspective on recent studies of social learning about foods by Norway rats. AB - Early naturalists explained field observations of social influences on animal learning in terms of spoken language, deliberate tuition of one animal by another, or intentional imitation. During the first half of the present century, experimental psychologists analyzed instances of social learning by animals in laboratory tasks as special cases of operant or classical conditioning. Neither of these traditional approaches provided much insight into the complex processes that often support animal social learning. By combining ethological focus on social learning as it occurs in natural habitat with analytical techniques developed in the psychological laboratory, contemporary researchers have made considerable progress in describing the many ways in which social interactions influence behavioural development in animals. The author's investigations of social influences on food selection by Norway rats provide one example of such an ethopsychological approach to the study of animal social learning. PMID- 2224639 TI - Additive latency effects of selective and nonselective restricted priming types. AB - The purpose of this investigation was to examine further the contention of Alain et al. (1988) that a third priming type exists, called nonselective restricted (NSR) and controlled by response probability, which is distinct from those types influenced by foreperiod duration (nonselective general priming) and prediction probability (selective priming). In a four-choice reaction time (RT) task, prediction probability (.5, .7, & .9, indicating the likelihood of a particular response) and response probability (.5, .9, denoting the likelihood that a response would be needed at all) exerted significant but noninteractive effects on RTs for prepared responses (most probable), suggesting that each of these probabilities influence different priming types (Sternberg, 1969; selective and NSR, respectively). This was further indicated by the fact that prediction probability, but not response probability, significantly altered RTs for the unprepared (lesser probable) responses. Finally, the hypothesized nonselective character of NSR priming (i.e., all outputs controlled by response probability are equally affected by its value changes) was supported when responses were equiprobable, and, while the null effect of response probability just mentioned seemingly argued against this property when selective priming took place, the interpretation provided herein negated this opposition. PMID- 2224640 TI - Search behaviour of cats (Felis catus) in an invisible displacement test: cognition and experience. AB - An invisible displacement test was administered to cats in order to test the hypothesis that search behaviour in this species is influenced by their limited capacity for object permanence as well as by their previous experience with the environment. Experiment 1 compared three groups of cats in a five-choice hiding task in which the hiding places could be discriminated by their spatial positions. Two groups received a visible displacement training before the invisible displacement test and one group did not. Experiment 2 compared two groups of trained subjects in the same task, but the hiding places could be discriminated by spatial and visual cues. The results confirmed that cats are unable to solve problems with invisible displacements. The visible displacement training improved their performance, but was not sufficient to make them succeed. Experience with the hiding potential of the covers also gives more persistence to search behaviour. Finally, the distribution of search attempts is not determined by the proximity to the target and is influenced only partially by the subjects' previous experience. Like Stage 5 infants, cats rely mainly on their immediate perception. They search for an object in the last location they have seen it disappear or under the nearest cover from this location. PMID- 2224641 TI - Seeing versus imagining movement in depth. AB - Subjects judged the quality of rigid motion between pairs of three-dimensional drawings that differed by a rotation in depth. The figures were aligned with, and rotated around, either the vertical axis or an axis that was oblique with respect to the XYZ co-ordinate system. Rated quality of motion decreased with increasing angular disparity between the figures and with decreasing stimulus duration, regardless of whether the figures were vertical or oblique. The same subjects then participated in a mental rotation task using the same stimuli and angular disparities. An effect of principal axis emerged, such that subjects took longer to make decisions about obliquely aligned stimuli than about vertically aligned stimuli, especially if they received the oblique stimuli first. These data imply that perceived versus imagined movement through the same trajectory involves different processes. Whereas the apparent motion system performs its computations relatively automatically, the processes involved in mental rotation are more strategic in nature. PMID- 2224642 TI - The object-line effect: is it attributable to intercontext differences or the structural properties of contexts and task demands? AB - Briefly presented target lines are reported more accurately when part of an object-like context than alone (Williams & Weisstein, 1978). Efforts to explain this effect have tended to focus on structural properties that contexts must possess in order to be effective in facilitating target-line discrimination (e.g., Weisstein, Williams, & Harris, 1982). Enns and Prinzmetal (1984) take issue with this approach. They propose that contexts differ more from one another than do target lines presented alone, and it is this fact, and not the general structural properties of contexts, that underlies their effectiveness. Two experiments examined intercontext differences and structural factors as determinants of context effectiveness. Subjects were found to use intercontext differences to narrow the range of possible alternatives, but when this factor was controlled, structural properties determined context effectiveness. The structural interpretation of context effectiveness was found not be as straightforward as generally assumed, however. A third experiment showed context effectiveness to be affected by the character of the discrimination task employed. PMID- 2224643 TI - Auditory grouping based on fundamental frequency and formant peak frequency. AB - The perceptual grouping of a four-tone cycle was studied as a function of differences in fundamental frequencies and the frequencies of spectral peaks. Each tone had a single formant and at least 13 harmonics. In Experiment 1 the formant was created by filtering a flat spectrum and in Experiment 2 by adding harmonics. Fundamental frequency was found to be capable of controlling grouping even when the spectra spanned exactly the same frequency range. Formant peak separation became more effective as the sharpness (amplitude of the peak relative to a spectral pedestal) increased. The effect of each type of acoustic difference depended on the task. Listeners could group the tones by either sort of difference but were also capable of resisting the disruptive effect of the other one. This was taken as evidence for the presence of a schema-based process of perceptual grouping and the relative weakness of primitive segregation. PMID- 2224644 TI - Pathogenicity of Staphylococcus lugdunensis, Staphylococcus schleiferi, and three other coagulase-negative staphylococci in a mouse model and possible virulence factors. AB - Staphylococcus lugdunesis and Staphylococcus schleiferi, two newly described species, have been isolated from numerous types of human infections. We compared the pathogenicity of 30 strains of S. lugdunensis, S. schleiferi, Staphylococcus epidermidis, Staphylococcus warneri, and Staphylococcus hominis, using a mouse model in which a foreign body preadhered with the test strain was implanted subcutaneously, followed by injection of the test strain. All five species of staphylococci produced abscesses. Staphylococcus epidermidis, S. schleiferi, and S. lugdunensis yielded species means of 76-91% abscess formation; 80-100% of the infected foreign bodies and tissues were culture positive. These three species were more virulent than S. warneri or S. hominis, which produced abscesses in 54 and 65% of mice, respectively; only 10-48% of the infected samples were culture positive. Transmission electron microscopy of pure cultures of selected strains showed that all species possessed glycocalyx. All species produced a variety of possible virulence factors, such as alpha and delta hemolysins, as well as the aggressins lipase and esterase. The production of exoenzymes did not always correlate with virulence as demonstrated by abscess formation in mice. PMID- 2224645 TI - Effect of various biophysicochemical conditions on toxigenicity of Vibrio cholerae 01 during survival with a green alga, Rhizoclonium fontanum, in an artificial aquatic environment. AB - Toxigenic and nontoxigenic strains of Vibrio cholerae 01 occur in the natural aquatic environment. It is not clear whether V. cholerae 01 lose toxigenicity and become nontoxigenic during survival in the aquatic environment as a result of the effect of various biophysicochemical conditions (e.g., sunlight, pH, temperature, competition with other bacteria for nutrients, etc.). Five toxigenic strains were exposed to artificial aquatic environments in the presence of a filamentous green alga. Rhizoclonium fontanum, and recovered after different time intervals (0 and 0.5 h, 3, 6, 9, and 15 days). This experimental system was exposed to sunlight and the V. cholerae 01 were in competition for nutrients with resident bacterial flora from R. fontanum. The toxigenicity of Vibrio cholerae 01 that were recovered at different time intervals was assessed by tissue culture assay using Vero cells. The toxigenicity of recovered strains was compared with that of the parent strains. The results demonstrated that toxigenic V. cholerae 01 are unlikely to lose their toxigenicity in aquatic environments as a result of the effects of various biophysicochemical conditions. These results are consistent with the hypothesis of environmental reservoirs of V. cholerae. PMID- 2224646 TI - Induction and repair of DNA strand breaks in Bacteroides fragilis. AB - Alkaline sucrose gradient sedimentation was used to establish whether strand breakage and repair take place in the DNA of UV-irradiated Bacteroides fragilis during the removal of pyrimidine dimers. A B. fragilis wild-type strain and two of its repair mutants, a mitomycin C sensitive mutant (MTC25) having wild-type levels of UV survival, and a UV-sensitive, mitomycin C sensitive mutant (UVS9), were investigated. Under anaerobic conditions, far-UV irradiation induced metabolically regulated strand breakage and resynthesis in the wild-type strain, but this was markedly reduced in both the MTC25 and UVS9 mutants. Approximately half of the strand breaks generated by the various strains were rejoined during further holding in buffer. Under replicating conditions, complete repair of strand breaks in the wild type was observed. Caffeine treatment under anaerobic conditions caused direct DNA strand breakage in B. fragilis cells but did not inhibit UV-induced breakage or repair. PMID- 2224648 TI - Early gastric cancer--making the asymptomatic better. PMID- 2224647 TI - Incidence of bacteriocinogeny among fresh isolates of Streptococcus mutans. AB - Among 139 Streptococcus mutans fresh isolates tested, using the deferred antagonism test and Streptococcus sanguis Ny 101 as the indicator strain, we observed that the frequency of detection of inhibition zones was reduced by 19% (from 53 to 34%) when arginine (1%) was used in the overlay agar. Among pigmented strains, the frequency of mutacin-like production was 70%. The frequency with which inhibition zones were detected varied from 7 to 91%, depending on the indicator strain used. These results indicate that the ability to detect the presence of mutacin-like substances varies widely and is dependent to a great extent on the methodology used. PMID- 2224649 TI - Reproductive conservation. PMID- 2224650 TI - Classification systems for colorectal carcinoma. PMID- 2224651 TI - Bikini appendectomy incision as an alternative to the McBurney approach for appendicitis. PMID- 2224652 TI - Canadian general surgery: alive and well. AB - General surgery in Canada is alive and well because general surgeons remain versatile and adaptable. If this were not the case, the specialty of general surgery would go the way of the dinosaur. The continuing evolution of general surgery can only be maintained by reviewing the following: (a) training; (b) continuing education; (c) maintenance of competence; (d) manpower and economic aspects; and (e) interaction of general surgeons with other surgeons and specialties. The Canadian Association of General Surgeons will continue to play a vital role in maintaining liaison between all types of general surgeons across the country and help, in any way possible, to support the ever-changing face of general surgery. PMID- 2224653 TI - Early gastric cancer: is it a distinct clinical entity? AB - Of 199 patients with gastric cancer seen at The Montreal General Hospital between 1970 and 1981, 104 were considered to have had a curative resection, and 26 of these were early gastric cancers (EGC). The authors compared early gastric cancers with advanced, but resectable, gastric cancers to determine whether EGC is a distinct entity or a stage in the progressive evolution of gastric cancer. They found that depth of invasion was the primary determinant of outcome, but that there was no discrete cut-off point between the depth of invasion associated with early and with advanced gastric cancers. The pathological features normally associated with a favourable prognosis in gastric cancer, such as absence of lymph-node metastases, an expanding growth pattern, intestinal metaplasia, and well-differentiated histologic features correlated highly with depth of invasion but did not appear to change abruptly between EGC and advanced resectable lesions. The authors conclude that EGC is not a distinct pathological or clinical entity but a stage in the progressive growth of gastric cancer. PMID- 2224654 TI - Management of pyogenic liver abscess in the era of computed tomography. AB - The advent of high-resolution imaging has allowed earlier diagnosis of pyogenic liver abscess. Because radiologically guided percutaneous drainage (PCD) of liver abscesses is controversial, the authors studied 40 patients with liver abscess admitted to the Toronto Hospital between 1982 and 1987 to determine the role of PCD versus operative drainage (OD). The diagnosis of pyogenic liver abscess was made at autopsy (4 patients), at laparotomy (6) or by radiologically guided aspiration of pus (30). Ultrasonography and computed tomography were highly sensitive (85% and 96% respectively) in detecting liver abscess. Of the 36 patients treated for liver abscess all received antibiotics intravenously; 31 also underwent a drainage procedure. Treatment with antibiotics alone was associated with a success rate of 80% and a death rate of 20%. The success rate for those who had PCD was 75% with a death rate of 13%; 2 patients in this group of 16 subsequently required OD for cure. In the 15 patients initially treated with OD, success and death rates were 87% and 13% respectively. For solitary abscesses, success rates wer comparable for PCD and OD (86% and 90% respectively). For unilobar multiple abscesses the success rate was 100% for both PCD and OD, but for bilobar multiple abscesses the rates were only 40% and 67% respectively. Complication rates were similar for both methods of drainage. The authors conclude that pyogenic liver abscess can now be safely and efficaciously managed with a combination of antibiotics and PCD. PMID- 2224655 TI - Ex-vivo microvascular reconstruction before renal allograft and autograft transplantation. AB - Microvascular reconstruction was performed ex vivo on 50 kidneys that had vascular anomalies or had sustained vascular injury during procurement before allograft transplantation or autotransplantation. The authors review the various surgical techniques used to facilitate the in-situ vascular anastomoses during transplantation and to salvage otherwise an unusable allograft. The complications associated with the microvascular repair were negligible. The authors conclude from the results of their study that ex-vivo microvascular reconstruction is a valuable adjunct to renal transplantation. PMID- 2224656 TI - Vagotomy and antrectomy revisited. AB - A retrospective review of 185 patients who underwent truncal vagotomy and antrectomy for duodenal ulcer disease was carried out to determine the mortality and morbidity of the procedure. There were no deaths within 30 days of operation and only one patient died while in the hospital (0.54%). Twenty-one patients (11.4%) suffered early morbidity, 3 of them requiring a second operation. Follow up was obtained in 83 patients and averaged 13.5 years. According to Visick's classification 75 patients (90.4%) were in class I or II; 5 patients (6%) were in class III and 3 patients (3.6%) in class IV. A recurrent ulcer developed in 2 of the 83 patients. In contrast, after highly selective vagotomy, the literature supports an unacceptable incidence of recurrent ulcer. Therefore, we must not prematurely cast aside vagotomy and antrectomy; it still remains a safe and acceptable procedure for duodenal ulcer disease. PMID- 2224657 TI - Ductal adenoma of the breast. AB - Ductal adenoma is a recently described benign tumour of the breast that can be mistaken for carcinoma in both frozen and paraffin sections. Such a case is presented. Fortunately a mastectomy was not performed, but the patient did undergo axillary node dissection. Surgeons and pathologists should familiarize themselves with this lesion so that patients do not have to undergo unnecessary mastectomies and axillary node dissections. PMID- 2224658 TI - Antibiotic handbook and pre-printed perioperative order forms for surgical antibiotic prophylaxis: do they work? AB - The authors attempted to compare the value of two strategies--an educational (antibiotic handbook) and a control (perioperative pre-printed physician order form, which contained antibiotic orders)--in modifying physicians' patterns of antibiotic prophylaxis for preventing infection in patients who undergo elective surgery. They reviewed the charts of 240 such patients on five different surgical services in one teaching hospital. Use of the antibiotic handbook (educational strategy) increased overall compliance with the recommended regimens from 11% to 18% (p = 0.06). The control strategy (perioperative pre-printed physician order form) increased compliance from 17% to 78% (p less than 0.01). PMID- 2224659 TI - Factors influencing the effectiveness of extracorporeal shock-wave lithotripsy of biliary duct calculi. AB - The authors examined the effectiveness of extracorporeal shock-wave lithotripsy on patients who had bile-duct stones. Thirty-eight patients were treated with an unmodified HM-3 Dornier lithotripter; 35 (92%) patients either passed the stone fragments spontaneously or had them reduced to a size which allowed removal by percutaneous or endoscopic techniques. As stone size increased so did the number of shocks required for satisfactory fragmentation, the number of treatments and the rate of post-treatment manipulation. The number of stones was not as important a variable as the authors expected. Pre-treatment sphincterotomy was not always necessary and was of no benefit in terms of spontaneous passage of fragments. Complications were minor. Extracorporeal shock-wave lithotripsy of stones throughout the biliary tree is a safe, effective and invaluable adjunct in the management of bile-duct stones. PMID- 2224660 TI - Is tube repair of aortic aneurysm followed by aneurysmal change in the common iliac arteries? AB - To address the concern that tube repair of an abdominal aortic aneurysm might be followed by aneurysmal change in the common iliac arteries, 23 patients who had undergone the operation were re-examined 3 to 5 years later. Although 9 had had minimal ectasia of these arteries preoperatively, in none of the 23 was there symptomatic or radiologic evidence of aneurysmal change on follow-up. Measurements of the maximum intraluminal diameters were made by computed tomography; they indicated no significant differences between the preoperative and follow-up sizes of the common iliac arteries. The variation in time to follow up also showed no significant correlation with change in artery diameter. PMID- 2224661 TI - Spontaneous rupture of splenic artery aneurysm: maternal and fetal survival. AB - Because the diagnosis of ruptured splenic artery aneurysm in pregnancy is seldom made before operation, maternal and fetal mortality continues to be high. The authors describe the case of a 22-year-old woman who had a ruptured splenic artery aneurysm at 32 weeks' gestation. The attending obstetrician considered this condition in the differential diagnosis and it was confirmed by ultrasonography, leading to a successful outcome. PMID- 2224662 TI - Cholesterol granuloma of the peritoneum. AB - Cholesterol granulomas are common in the mastoid region but have rarely been reported in other areas. The authors report the case of a 40-year-old man who had a cholesterol granuloma of the peritoneum. They discuss the morphology of the condition and the difficulties of diagnosis. It is likely that chronic or recurrent inflammation plays a major role in the pathogenesis and that, when dealing with such lesions preoperatively or intraoperatively, a radical approach may not be necessary. PMID- 2224663 TI - Imipenem versus tobramycin--antianaerobe antibiotic therapy in intra-abdominal infections. AB - The authors compared broad-spectrum monotherapy with imipenem to an aminoglycoside-based antibiotic regimen for the management of intra-abdominal infections. One hundred and four patients who had intra-abdominal infection were randomly allocated to receive imipenem (52) or tobramycin plus clindamycin or metronidazole (52). Patients treated with imipenem had fewer febrile episodes and occurrences of breakthrough bacteremia, less antibiotic resistance and need for drug change; their hospital stay was shorter. The death rate from sepsis was 4% in patients who received imipenem and 13% in those who received the combined regimen (p = 0.08). Treatment was successful in 79% of patients on imipenem versus 67% of those receiving an aminoglycoside. Patient stratification by the APACHE II system and probability of death calculation using delayed-type hypersensitivity scores predicted a similar death rate for the two treatment groups. Imipenem appears to be a safe and efficacious alternative broad-spectrum antibiotic for treating patients who are seriously ill with intra-abdominal infection. PMID- 2224664 TI - Small-bowel lipoma: an uncommon cause of obstruction. AB - Small-bowel tumours are an uncommon cause of small-bowel obstruction. The symptoms are unusually nonspecific and intermittent. Contrast studies of the small bowel are the best means of delineating the lesion. The authors present a case in which obstruction was treated with small-bowel resection, and they give a brief account of the occurrence of small-bowel tumours in a major teaching hospital. PMID- 2224665 TI - Preventing alcohol problems: preparing physicians for their roles and responsibilities. PMID- 2224666 TI - Disease transmission and cardiopulmonary resuscitation. Emergency Cardiac Care Committee, Heart and Stroke Foundation of Canada. PMID- 2224667 TI - Effects of patient, physician and hospital characteristics on the likelihood of vaginal birth after previous cesarean section in Quebec. AB - Repeat cesarean section is a major factor contributing to the rising cesarean section rate. Although vaginal birth after a previous cesarean section (VBAC) is advocated in most cases, it has not yet been adopted as widespread policy. In a case-control study we compared 400 women in Quebec who underwent VBAC with 1600 women who had a repeat cesarean section from 1985 to 1987 in an attempt to identify factors that favour vaginal delivery. Using both simple and multiple logistic regression analyses we examined the effect of independent variables linked to the patients (two variables), the attending physicians (seven) and the hospitals (two) on the dependent variable (type of birth) with the use of odds ratios. We found that the physician characteristics related to type of practice and the degree of hospital specialization were significant factors in predicting the type of delivery. Women who gave birth vaginally were more likely than those who had a repeat cesarean section to be attended by a physician with a specialized practice and to give birth in a hospital providing an intermediate or high level of care. This suggests that VBAC is still perceived as a high-risk option and is managed by only a minority of specialized obstetricians. PMID- 2224668 TI - Hospital-based utilization management: a cross-Canada survey. AB - Utilization management attempts to measure, understand and, when appropriate, reduce hospital use. We conducted a telephone survey to determine the status of utilization management in Canadian hospitals. The sample comprised a random selection of 30% of acute-care hospitals with over 100 beds for adults in Ontario and Quebec and all such hospitals in the other provinces. Of the 123 chief executive officers contacted 99 (80%) claimed to have a utilization management program. Of those, 90 (91%) agreed to participate in an in-depth survey or to designate a senior administrator to be interviewed who was most knowledgeable about the program. High occupancy rates and funding issues were the most common environmental triggers for the development of utilization management programs; funding issues were listed more frequently by respondents in Ontario than by those elsewhere (p = 0.0008). Retrospective review alone was used in half of the hospitals, concurrent review or some mixed approach being used in the other half. Ontario and the Atlantic provinces were more reliant than the rest of the country on retrospective review alone (p = 0.0032). Most of the hospitals used peer review and education to stimulate corrective action. Of the respondents 67% indicated that the medical staff supported the utilization management program, and 53% reported that the program had a positive impact on the relationship between administrative and medical staff. Most of the respondents were unsure of the program's impact on the quality of care or the rate of unnecessary hospital admission. However, retrospective review alone was found to be less successful in reducing inappropriate utilization than either concurrent review or combined review (p = 0.0048). PMID- 2224669 TI - Acute interstitial nephritis due to 5-aminosalicylic acid. PMID- 2224670 TI - Endothelial cell growth factors in atherogenesis. PMID- 2224672 TI - The role of medical schools in the prevention of alcohol-related problems. AB - There is agreement that physicians can play a major role in the prevention of alcohol problems among their patients and that medical schools should prepare physicians for this role by teaching three major subject areas: knowledge, attitudes and clinical skills. Despite this agreement and the acknowledged high prevalence of alcohol problems in clinical populations, medical school coverage of these problems is not proportional to their importance. Barriers to adequate coverage of alcohol problems are traditional attitudes, confusion as to whether such problems are "medical" and lack of adequate faculty role models. These problems could be remedied by encouragement and training of interested faculty members, establishment of substance abuse centres in university medical schools, integration of alcohol-related material with relevant topics in all departments and inclusion of alcohol-related questions on medical qualifying exams. PMID- 2224671 TI - The physician's role. AB - Physicians can play an important role in society's response to alcohol problems. In diagnosis, alcohol problems among patients are frequently overlooked. Physicians should routinely ask patients about alcohol intake. In light of evidence on the effectiveness of brief interventions, especially with heavy drinking but nondependent patients, physicians' treatment efforts should be focused in this direction. Patients who are alcohol dependent might best be treated by nonphysicians. Research contributions of physicians should be concentrated on topics for which physician input is needed: longitudinal studies of health consequences, factors contributing to mortality and health service costs, biochemical markers of alcohol use and basic pharmacology. Strong evidence links population alcohol consumption levels to overall harm. Therefore, prevention efforts should be aimed at the population as well as at people who may be at risk. Physicians can contribute to these efforts by influencing public policy and by setting healthy examples in their own alcohol use. PMID- 2224673 TI - Spectrum of drinkers and intervention opportunities. AB - Most adults in North America are either light drinkers or abstainers, so alcohol does not cause them problems. However, a small but often highly visible minority- approximately 5% of the adult population--show major symptoms of alcohol dependence. Between these extremes, there is a sizable group of about 20% of the population, particularly young men, who are drinking at risk levels and have encountered some problems related to their alcohol use. Traditionally, physicians' efforts have focused on diagnosing and treating patients with a substantial history of alcohol dependence, and relatively little attention has been given to early intervention with nondependent problem drinkers, such as identifying patients who present in primary care settings with alcohol-related morbidity or an accidental injury. Recent evidence indicates that early intervention by primary care physicians is an effective strategy for reducing alcohol problems among patients. PMID- 2224675 TI - Brief intervention strategies for harmful drinkers: new directions for medical education. AB - Recent advances in the technology of behavioural interventions for harmful drinkers have created a new role for clinical practice and new challenges for medical education. Several reports from expert committees have recommended new initiatives in the secondary prevention of alcohol problems through physician based interventions at the primary care level. The conceptual and scientific bases for these recommendations are discussed in terms of recent studies of harmful and hazardous drinkers. The behavioural principles thought to account for the effectiveness of brief interventions are explained. Despite these promising developments, difficulties are inherent in the introduction of new technologies, especially behavioural technologies, into medical practice. A major challenge to medical education will be the development of academic programs that not only teach skills and competencies in secondary prevention but also deal with the socialization of physicians as behavioural practitioners. PMID- 2224674 TI - Early identification of alcohol problems. AB - A high proportion of patients seen in clinical practice have an underlying alcohol problem. This is often difficult to detect, but failure to make the diagnosis may result in unnecessary investigations and inappropriate treatment. Furthermore, there is now good evidence of the effectiveness of brief intervention for problem drinking when it is still at an early stage. Several questionnaires and procedures based on clinical examination findings and laboratory tests are available to help in early diagnosis. They can be incorporated into the standard medical assessment and form the basis for screening programs for health risk factors. PMID- 2224676 TI - Preventing alcohol problems: survey of Canadian medical schools. AB - In preparation for a national conference on medical education in the prevention of alcohol problems, a survey of conference participants was conducted. Participants were undergraduate and postgraduate representatives from each Canadian medical school and representatives from 11 provincial and territorial alcohol and other drug agencies. There was agreement that physicians and medical schools have important roles in prevention and treatment of alcohol problems, with "traditional" medical roles seen as the most important. Current training is variable and was seen as inadequate, with more time devoted to treatment than prevention. To correct this situation, renewed priorities and faculty leadership are needed. Respondents felt that there should be uniform standards for assessing undergraduate students' skills in dealing with alcohol problems. Provincial alcohol and other drug agencies are underused in medical education in the prevention and treatment of alcohol problems. PMID- 2224677 TI - The development of medical education on alcohol- and drug-related problems at the University of Toronto. AB - Medical education on alcohol- and drug-related problems at the University of Toronto covers undergraduate, residency and graduate programs, a result of collaboration since 1959 between the university and the Addiction Research Foundation of Ontario. An undergraduate core curriculum, developed in the early 1970s, is offered in year 2; it has been supplemented by electives, selectives and comprehensive clinics. The undergraduate program is rated highly by students; since 1978, 3024 have completed the core program. Residency training started in 1974 and is available through electives lasting from 1 to 12 months in internal medicine, psychiatry, and family and community medicine. To date, 370 residents have completed one of these electives; 129 have completed graduate programs in which their theses concerned alcohol- and drug-related topics, and there have been an additional 13 research and postdoctoral fellows. Despite the progress, there is still a need to improve and expand the undergraduate and residency programs and to develop an effective program of continuing medical education. The goals should be to ensure that, as far as possible, all medical graduates from the University of Toronto have the knowledge, attitudes, skills and behaviours needed to contribute effectively to the prevention and treatment of alcohol- and drug-related problems in their chosen field of practice and to avoid problems from their personal use of alcohol and other drugs. PMID- 2224678 TI - Medical education for alcohol and other drug abuse in the United States. AB - Initiatives by individuals, private foundations and government have led to improvements in the United States in medical education dealing with alcohol and drug-related problems. Progress has been made, particularly in the past 5 years, in developing new medical school curricula and in faculty development. Greater activity by national professional organizations has helped raise the priority of training in alcohol- and drug-related areas for undergraduate and postgraduate medical education. As an example, Project ADEPT (Alcohol and Drug Education for Physician Training in primary care) at Brown University in Providence, Rhode Island, is described. The importance of positive and motivated faculty role models and of skills training is emphasized. PMID- 2224679 TI - An agenda for action. PMID- 2224680 TI - Risk of aerosol inhalers. PMID- 2224682 TI - The Ottawa Heart Institute: it's good, but can we afford it? PMID- 2224681 TI - New drugs for hypertension: should data precede conclusions? PMID- 2224683 TI - Dr. Maude Abbott deserves better. PMID- 2224685 TI - Hypernatremia associated with N-acetylcysteine therapy for meconium ileus in a premature infant. PMID- 2224684 TI - Decoding prescriptions. PMID- 2224687 TI - The fetus as a person. PMID- 2224686 TI - Tryptan: no association with eosinophilia-myalgia syndrome. PMID- 2224689 TI - Computer multitasking with Desqview 386 in a family practice. PMID- 2224688 TI - Alcohol consumption and plasma lipoproteins. PMID- 2224691 TI - Physician attrition and future manpower needs. PMID- 2224690 TI - Medical ethics and women. PMID- 2224693 TI - Nuclear medicine physicians and radiation safety. PMID- 2224692 TI - Women and HIV infection and AIDS in Canada: should we worry? PMID- 2224694 TI - Zidovudine (Retrovir) update. AB - Zidovudine (AZT) is the first antiretroviral agent to be licensed for the treatment of human immunodeficiency virus (HIV) infection. Since the initial placebo-controlled trial showing improved survival among patients with acquired immunodeficiency syndrome (AIDS) or symptomatic HIV infection (AIDS-related complex [ARC]) zidovudine has been evaluated in other stages of HIV infection. This review offers physicians who treat patients with HIV infection a comprehensive analysis of the current data on the clinical efficacy of zidovudine in various stages of HIV infection and on zidovudine's adverse effects. After a search of MEDLINE for pertinent articles published since 1985, controlled studies and studies of long-term zidovudine therapy, of zidovudine therapy for HIV related conditions and of the incidence and management of adverse reactions were evaluated. In addition, abstracts from international meetings were reviewed. No significant difference in clinical outcome was found between high-dose and low dose zidovudine therapy, but there were significantly fewer toxic effects in the low-dose group. In two other studies zidovudine was found to delay disease progression in patients with asymptomatic or mildly symptomatic HIV infection who had an absolute CD4 count of less than 0.5 x 10(9)/L; the low incidence of adverse reactions may have been due to either the early stage of the infection or the low dose used. The demonstration of zidovudine-resistant isolates after at least 6 months of therapy has yet to be correlated with clinical deterioration. When to begin zidovudine therapy among asymptomatic patients with a CD4 count of less than 0.5 x 10(9)/L remains unclear. Zidovudine can be used safely to delay progression to AIDS or ARC in certain patients with asymptomatic or mildly symptomatic HIV infection and can prolong survival in those with more severe infection. Further studies are necessary to identify indicators that could better define when to start treatment and how to alleviate toxic effects. Combination therapy with such agents as interferon alpha may become the preferred choice of therapy to prevent toxic effects and zidovudine resistance. Zidovudine prophylaxis has been used after HIV exposure. Although studies with animal models have had encouraging results infection has occurred despite immediate prophylaxis and thus further investigation is required. PMID- 2224695 TI - An anonymous seroprevalence survey of HIV infection among pregnant women in British Columbia and the Yukon Territory. AB - We performed an anonymous seroprevalence survey of human immunodeficiency virus (HIV) type 1 infection through HIV antibody testing of blood samples from 22,512 women aged 15 to 44 years receiving prenatal care in British Columbia and the Yukon Territory from Mar. 15 to Sept. 30, 1989. Of the samples six were confirmed to be HIV positive; this yielded a crude overall seroprevalence rate of 2.7 per 10,000 pregnant women (95% confidence interval [CI] 1.0 to 5.8). All of the positive samples were from women 20 to 29 years of age; four were from Vancouver, one was from Victoria, and one was from elsewhere. The highest seroprevalence rates were among women aged 15 to 29 years in Vancouver and Victoria (7.2 and 9.4 per 10,000 pregnant women respectively). Thus, 1 in 1300 pregnant women in that age group in the metropolitan areas of British Columbia was HIV positive. Application of seroprevalence rates to the total female population in British Columbia and the Yukon Territory revealed that as many as 401 women had HIV infection in 1989. Our estimates likely represent the minimum. As a subset of women of childbearing age pregnant women are likely at lowest risk of HIV infection, and so the true number of women 15 to 44 years of age with HIV infection is probably several times higher. Our study has provided a baseline assessment and will be repeated annually to analyse trends in HIV seroprevalence among pregnant women in British Columbia and the Yukon Territory. PMID- 2224696 TI - Five-year results of the peer assessment program of the College of Physicians and Surgeons of Ontario. AB - The office practices of 918 physicians selected through stratified random sampling from the College of Physicians and Surgeons of Ontario (CPSO) registry were assessed by peers and the Peer Assessment Committee of the CPSO from 1981 to 1985. The sample comprised 662 general practitioners (GPs) and family physicians (FPs) and 256 specialists in 11 fields. Of the physicians 749 (82%) had neither deficient records nor an unsatisfactory level of patient care. Of the GPs and FPs 97 (15%) had serious deficiencies in one or both areas, as compared with 4 (2%) of the specialists (p2 less than 0.00001). The proportions of certificants of the Royal College of Physicians and Surgeons of Canada and of the College of Family Physicians of Canada (CFPC) with serious deficiencies were low (2% and 3% respectively). Three statistically significant predictors of physician performance were found among the GPs and FPs: age, CFPC membership status and type of practice. Of the 56 physicians who were reassessed 6 to 12 months later 29 (52%) had made the improvements recommended by the committee. Our findings demonstrate the need, feasibility and acceptance of a peer assessment program of office practices in Ontario. PMID- 2224698 TI - Women focus of this year's World AIDS Day. PMID- 2224697 TI - Catatonic reaction to omeprazole and disulfiram in a patient with alcohol dependence. PMID- 2224699 TI - Guides, manuals for dealing with AIDS in workplace now available. PMID- 2224700 TI - Role of physicians key in national AIDS strategy, Ottawa says. PMID- 2224701 TI - Justice minister tries to allay doctors' fears about abortion bill. PMID- 2224703 TI - Cocaine users may not fit MDs' stereotype, FPs warned. PMID- 2224702 TI - Restraint is needed in our use of patient restraints. PMID- 2224704 TI - HIV antibody testing: CMA counselling guidelines. PMID- 2224705 TI - Risk factors for HIV seropositivity among people consulting for HIV antibody testing. PMID- 2224706 TI - Abortion and the DPG ratio. PMID- 2224707 TI - Third World aid. PMID- 2224708 TI - Medical licensure: let's not lose sight of the objective. PMID- 2224710 TI - Continuity of care: its importance in maintaining a teaching family practice. PMID- 2224709 TI - Assisting suicide. PMID- 2224711 TI - Guidelines for the release of laboratory test results, reports and specimens to patients, interested groups and other institutions. Canadian Association of Pathologists. PMID- 2224712 TI - Report of the Expert Advisory Committee on the Use of Drugs in the Treatment of Abuse and Dependence to Narcotic and Controlled Drugs. PMID- 2224713 TI - Periodic health examination, 1990 update: 4. Well-baby care in the first 2 years of life. Canadian Task Force on the Periodic Health Examination. PMID- 2224714 TI - Electrical safety in patient care areas. PMID- 2224716 TI - HIV infection among Quebec women giving birth to live infants. AB - This is the first anonymous unlinked seroprevalence study in Canada to use serum samples from newborns to determine the seroprevalence rate of human immunodeficiency virus (HIV) infection among childbearing women. Of the 68,808 samples tested 42 were confirmed as positive, for an overall crude seroprevalence rate of 6.1 per 10,000 live births (95% confidence interval [CI] 4.4 to 8.3), or 1 woman in 1638. Women who lived on Montreal island had an overall rate of 17.9 per 10,000 live births (95% CI 12.2 to 25.4), or 1 woman in 559. We observed a significant association between revenue index and seroprevalence; the rates were as high as 46.4 per 10,000 live births (95% CI 18.7 to 95.3), or 1 woman in 216, for Montreal island postal code areas with revenue indexes 20% or more below the provincial median. Extrapolation of the data suggested that 56 women with HIV infection gave birth to a live infant during 1989 in Quebec. Even though attempts to generalize the data from childbearing women to women of childbearing age have an inherent conservative bias, the results of our study suggest that 988 women (95% CI 713 to 1336) aged 15 to 44 years in Quebec had HIV infection in 1989. The actual number is likely substantially higher. The need for well-designed, creative interventions to prevent further HIV transmission to women is evident. Planning for the provision of medical and psychosocial services sensitive to specific needs of women who are already infected should start immediately. PMID- 2224718 TI - Trends in Canadian tobacco consumption, 1980-89. PMID- 2224715 TI - Early detection and treatment of hyperlipidemia: physician practices in Canada. AB - We surveyed primary care physicians in Canada to determine their current practices regarding the detection and treatment of hyperlipidemia in asymptomatic adults 20 years of age or more and to determine the role of selected patient characteristics (age, sex and the presence of coronary heart disease [CHD] risk factors) in their management decisions. The self-administered questionnaire was completed by 428 of 804 family physicians and general practitioners. The proportion of physicians who reported having tested at least 50% of their adult patients varied from 29% to 85% and was related to the number of CHD risk factors present and the patient's age. The proportion of respondents who reported starting dietary or drug therapy among patients with a cholesterol level of 6.2 mmol/L or less increased as the number of CHD risk factors increased and was not related to patient age or sex. According to the factors examined our results suggest that primary care physicians in Canada select patients for screening and treatment mainly on the basis of CHD risk factors present and that their approach is more conservative than that recommended by the Canadian and US consensus conferences. PMID- 2224719 TI - Canadian lab to produce HIV immunogen for clinical trials. PMID- 2224721 TI - "Come south, young doctor", Humana tells Canadian MDs. PMID- 2224717 TI - Susceptibility of Haemophilus influenzae to antimicrobial agents used in Canada. Canadian Study Group. AB - We evaluated the incidence of Haemophilus influenzae resistance to selected antimicrobials used in Canada. From 1985 to 1987, 2503 H. influenzae isolates obtained in 14 hospitals across Canada were sent to the Centre hospitalier de l'universite Laval (CHUL) for identification, serotyping, biotyping and testing for beta-lactamase production. Susceptibility tests were done with the use of 12 antibiotics. Of the strains 424 (16.9%) produced beta-lactamase; the proportion varied from 12.8%, in Newfoundland, to 19.6%, in Ontario. Of the strains 18.3% were type b; 19.4% of those produced beta-lactamase. Almost 82% of the strains were not type b. The proportion of beta-lactamase-producing strains varied according to the isolation site, from 15.3% in the respiratory tract to 25.6% in the blood. The overall level of resistance was 19.3% to ampicillin, 24.2% to erythromycin, 3.8% to trimethoprim-sulfamethoxazole, 1.7% to amoxicillin potassium clavulanate, 1.4% to cefaclor, 1.3% to tetracycline, 1.0% to rifampin, 0.7% to cefuroxime and 0.1% to cefamandole. Disc diffusion susceptibility testing revealed 64 strains (2.6%) that did not produce beta-lactamase but were resistant to ampicillin and 9 (0.4%) that produced beta-lactamase but were susceptible to ampicillin. The results of beta-lactamase production tests were identical regardless of whether the tests were done by the CHUL or by the other hospitals, but there was a marked difference in the susceptibility test results between the CHUL and the other centres. Our results suggest that the level of resistance of H. influenzae to antibiotics is increasing in Canada and that the initial choice of drug therapy may have to be modified. PMID- 2224720 TI - The bottom line. PMID- 2224723 TI - Report on UK cancer survival rates raises questions about alternative medicine. PMID- 2224722 TI - Cleveland's physicians say no to Canadian-style health care. PMID- 2224724 TI - Physician remains defiant in bid to withhold defence portion of income tax. PMID- 2224725 TI - The unkindest cut of all. PMID- 2224726 TI - Stand-alone HIV clinic expected to save money, help patients. PMID- 2224728 TI - History and modern concepts. PMID- 2224727 TI - Dr. Ignatz Nascher and the birth of geriatrics. PMID- 2224729 TI - Animal models for amyloidosis. PMID- 2224730 TI - Treatment. PMID- 2224731 TI - Clinical features of cutaneous amyloidoses. PMID- 2224732 TI - Epidemiology of primary cutaneous amyloidoses in southeast Asia. PMID- 2224733 TI - Epidemiology of primary cutaneous amyloidoses in South America. PMID- 2224734 TI - Histopathology of primary cutaneous amyloidoses and systemic amyloidosis. PMID- 2224735 TI - Electron microscopy of primary and secondary cutaneous amyloidoses and systemic amyloidosis. PMID- 2224737 TI - Elastic fiber and cutaneous amyloidoses. PMID- 2224736 TI - Amyloid P-component and the skin. PMID- 2224738 TI - Mucocutaneous manifestations in systemic amyloidosis. PMID- 2224739 TI - Collagen and cutaneous amyloidoses. PMID- 2224740 TI - Tissue culture and cutaneous amyloidoses. PMID- 2224741 TI - Unique aspects of diabetes mellitus in the elderly. AB - Diabetes mellitus is a common condition in the geriatric population. In older subjects it may present in unusual ways and may be associated with unusual conditions. Hyperglycemia produces a variety of effects, including osmotic diuresis and cognitive dysfunction, which seriously impair the quality of life of the older individual. Older diabetics need to have their diabetes well controlled. The approach to diabetic control in older individuals is similar to that in younger individuals, with some notable exceptions. PMID- 2224743 TI - Atypical presentation of diabetes mellitus in the elderly. AB - Diabetes mellitus is a common problem affecting the elderly. Unfortunately, many people learn they have a problem only after late sequelae of the disease are present. Classic symptoms of hyperglycemia may be lacking or confused with other age-prevalent problems or the aging process itself. Any change in condition, whether medical or psychological, deserves a glucose control assessment. Because of problems in diagnosis, glucose screening has been advocated. Only by diagnosing diabetes mellitus early can late complications be prevented and a high quality of life assured. PMID- 2224742 TI - Epidemiology of diabetes mellitus among the elderly in the United States. AB - Diabetes mellitus is one of the most common chronic diseases affecting the elderly in the United States. It has been diagnosed in 9.6% of people 65 years of age and older, and an additional 9.3% meet oral glucose tolerance test criteria for the disease but have not been diagnosed. Taken together, diagnosed and undiagnosed diabetes affects almost one in every five people 65 years of age and older. An additional 23% of the elderly meet diagnostic criteria for impaired glucose tolerance, a condition that conveys excess risk for macrovascular disease. Prevalence of diagnosed diabetes in the elderly is expected to increase 44% in the next 20 years, to an estimated population of 3.9 million people. Elderly people with diabetes make an average of 3.7 visits per year to physicians specifically for care of their diabetes. Over 80% of this care is delivered by general and family physicians and internists. About 30% of diabetics 65 to 74 years of age are hospitalized each year, a rate that is almost twice that of elderly people without diabetes. Cardiovascular and peripheral vascular complications are often twice as prevalent as among people without diabetes. Risk factors for macrovascular disease are also highly prevalent among the elderly, including obesity, hypertension, and hypercholesterolemia. Three fourths of deaths of diabetic patients 65 years of age and older are caused by diseases of the circulatory system, primarily ischemic heart disease and stroke. The death rate from cardiovascular disease among elderly diabetic patients is twice that of people without diabetes in the same age range. PMID- 2224744 TI - Cognitive and affective disorders in elderly diabetics. AB - In non-insulin-dependent diabetes mellitus, performance of complex cognitive tasks requiring the storage and retrieval of new information is poorer than in age-matched controls. By contrast, performance of less demanding tasks such as immediate memory and simple reaction time is essentially equivalent for NIDDM patients and controls. This pattern parallels the cognitive change observed with normal aging, in which age differences are minimal on less demanding immediate memory tasks but older adults perform more poorly than young adults on secondary or long-term memory tasks. Age-related changes in cognitive performance have been attributed to a reduction in processing resources or working memory capacity. Although the explanation for NIDDM-related deficits remains to be identified, reduced glucose control and elevated levels of triglycerides appear to play some role in cognitive impairment. Non-insulin-dependent diabetes is associated not only with elevated levels of depression, but with an increased frequency of self reported memory problems. Moreover, elevated levels of depression are associated with various indicators of neuropathy and with significant reductions in self regulated control of glucose at the time of medical office visits. Diabetic patients may perceive less control over their lives as a result of the many restrictions associated with the disease. When provided with the opportunity to exercise control, however, performance on many cognitive tasks can be improved in NIDDM as well as in age-matched controls. This suggests that by providing NIDDM patients with opportunities to exercise increased control over their lives it may be possible to enhance motivation and to increase the likelihood of the patient's adopting more effective self-regulatory behaviors. PMID- 2224745 TI - Foot ulceration and infections in elderly diabetics. AB - Foot lesions occur commonly among patients with diabetes, particularly the elderly and those with sensory neuropathy. Because of serious or recurrent infections and impaired healing processes, initially trivial lesions may progress to chronic nonhealing wounds, gangrene, or untreatable infections that can lead to limb amputation. Strategies to prevent amputation depend on understanding the multifactorial nature of diabetic foot disease; providing effective ongoing preventive care, including patient education; and prompt and aggressive treatment of foot lesions when they occur. The approach to treatment of infections depends on many factors, including the severity of the soft tissue infection, whether or not underlying bone or joints are involved, the types of infecting organisms, the patient's social situation, and his other medical problems. Proper diagnostic studies followed by appropriate antimicrobial therapy and local wound care can usually lead to resolution of these potentially serious infections. PMID- 2224746 TI - Diabetes-related impotence in the elderly. AB - Because many elderly men with chronic illnesses such as diabetes have multiple causes contributing to their impotence and may still retain an interest in sexual activity, those who still are unable to adequately perform sexually after treatment of their medical problems should be informed of the alternative methods of treatment of their impotence or alternative methods of sexual fulfillment and gratification and, when necessary, should be offered supportive counseling and psychotherapy. PMID- 2224747 TI - The diabetic hyperosmolar state. AB - The diabetic hypersomolar state is defined by a serum glucose greater than 600 mg/dl and a serum osmolarity greater than 320 m Osm/L. Ketoacidosis or lactic acidosis may co-exist with DHS in the same patient. The incidence of this acute complication of diabetes is high enough (17.5 cases per 100,000 person-years) for primary care physicians to encounter a case every year or two. Predisposing factors include older age, female sex, nursing home residence, and infection. A substantial proportion of cases occur in patients with no prior history of diabetes. Common presenting signs include fatigue or weakness, polydipsia, polyuria, nausea, and alteration of consciousness. The mainstay of therapy is intravenous fluid replacement with close monitoring of glucose and electrolytes in a hospital setting. Current mortality figures are high, at 10% to 20%, and the chance of survival is adversely affected by older age, higher osmolarity, and the presence of an associated severe illness. Prevention includes screening for diabetes, educating diabetic patients and their care givers about the symptoms of hyperglycemia, prompt treatment of any infection in a diabetic person, avoidance of drugs that increase carbohydrate intolerance in diabetic people, and encouraging compliance with treatment of diabetes. PMID- 2224748 TI - Renal complications in non-insulin-dependent diabetes mellitus. AB - Renal failure among elderly individuals with diabetes is a substantial clinical and public health problem. These individuals account for the majority of renal failure among people with diabetes mellitus in the United States. Although limited population-based data directly provide evidence regarding the incidence of and risk factors for ESRD, extant data suggest that blacks and Pima Indians have a markedly increased risk of ESRD compared with whites in the United States. Proteinuria and microalbuminuria appear to be extremely common in elderly individuals with NIDDM and are strongly associated with overall survival, cardiovascular morbidity and mortality, and the development of ESRD. Although randomized clinical trials are needed to test intervention strategies to reduce morbidity and mortality associated with renal disease among individuals with NIDDM, extant data suggest that management efforts directed at hypertension control and, possibly, moderate restriction of protein intake may be important therapeutic modalities for prevention of renal disease and its associated sequelae among elderly individuals with diabetes. PMID- 2224749 TI - Ocular problems in older Americans with diabetes. AB - Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy from persons with diabetes of older onset whose average age was 65.4 years indicate that 9.9% of the men and 13.3% of the women had some degree of visual impairment, and 1.4% of men and 1.7% of women were legally blind (with an visual acuity of 20/200 or worse in the better eye). Poorer visual acuity was strongly associated with increasing duration of diabetes, but age was also an important factor, with rates of legal blindness increasing markedly after the seventh decade of life in groups of any duration. Conditions responsible for legal blindness were diabetic retinopathy or maculopathy, cataracts, glaucoma, and macular degeneration. Incidence of blindness 4 years after the initial evaluation was related to insulin use, younger age at examination, longer duration of diabetes, and more severe retinopathy at baseline. Worsening of vision was related to higher levels of glycosylated hemoglobin and the presence of macular edema on diabetic retinopathy at baseline. These data indicate that there is a high prevalence of ocular problems among people with diabetes of older onset. The practitioner should suggest to these patients that, soon after the diagnosis of diabetes, they have an ophthalmologic evaluation to determine whether asymptomatic problems are present. This action may lead to timely intervention to prevent loss of vision in some patients. PMID- 2224750 TI - Screening for non-insulin-dependent diabetes mellitus in the elderly. AB - There are three major obstacles to a recommendation for screening the elderly for NIDDM. The first is the conflicting evidence as to whether early detection and treatment reduce complications. The second is that treatment of hyperglycemia with attainment of euglycemia is difficult to achieve in the elderly. Nondrug therapy often fails because of lifelong eating habits, denture problems, fixed income, and physical handicaps. Drug therapy is fraught with the dangers of hypoglycemia and drug interactions. Compliance with therapy often is poor and leads to conflicts between physician and patient that may be detrimental in the treatment of other diseases in which intervention has proven worthwhile. The third obstacle is the lack of data regarding the adverse effects of labeling and noncompliance issues in the face of a positive screening test. Because obesity is a risk factor for NIDDM and hypertension in conjunction with NIDDM leads to atherosclerosis, screening and treatment for these two conditions are warranted whether or not NIDDM is present concurrently. Medicine is in a dynamic state of flux and, undoubtedly, conflicts over the benefits of early treatment and patient compliance will be resolved. Until then, there is no justification for screening for NIDDM in the elderly. PMID- 2224751 TI - Effect of physical activity on age-related glucose intolerance. AB - Glucose tolerance tends to deteriorate with age, but a major portion of this deterioration can be explained by changes in other age-related variables- obesity, physical inactivity, use of medications, and chronic illness. This review has focused on the role that physical activity can play in preventing the age-associated decline in glucose tolerance. Pathophysiologically, most of the decline in glucose tolerance appears to be caused by a decrease in insulin action with aging. Given that it has been shown that exercise increases insulin action, there is a plausible biologic mechanism explaining the observed association between physical activity and the preservation of insulin sensitivity and glucose tolerance with aging. Finally, it appears from the published data that it is life long maintenance of physical activity, beginning long before individuals reach the geriatric age group, that will be most beneficial to the health of aging Americans. PMID- 2224752 TI - Functional status measurement in elderly diabetic patients. AB - Elderly diabetic subjects are at particularly high risk for a wide range of physical, emotional, cognitive, and social functional impairments. The primary physician therefore is well advised to systematically assess the functional status of such patients, either by traditional informal methods or, preferably, by implementing some systematic approach. One practical three-step approach involves identifying which abilities are particularly important to or endangered in a given patient, listing these on the Diabetes Data Flow Sheet and briefly reviewing them with the patient on a periodic basis, and using a functional problem list as a guide to effective and timely intervention and follow-up. PMID- 2224753 TI - Nutritional status and dietary management of elderly diabetic patients. AB - Dietary treatment of diabetes has long been the cornerstone of management of this common disease. Recent recommendations to increase the proportion of carbohydrate with concomitant reduction of dietary fat appear to be prudent, but scant data are available to support this supposition in the elderly. Modification of the source of carbohydrate as a means of providing better blood glucose control is based on limited data in controlled settings and needs to be tested in community settings before widespread alterations in the dietary composition can be widely recommended. Current recommendations for protein composition of the diet are probably adequate for the elderly diabetic patient who does not have obvious protein depletion. General guidelines for the dietary management of elderly diabetic patients are summarized in Table 5. Management of the elderly diabetic patient presents a strong challenge to the physician. Dietary recommendations for such patients should be highly individualized; patients' food preferences, ethnic background, financial resources, and support system should be taken into consideration. Simple recommendations drafted with the help of the patient are more likely to be successful. The elderly are often at risk for nutritional deficiency, and the presence of chronic disease such as diabetes profoundly affects metabolism, putting these individuals at still higher risk. Unfortunately, our current understanding of this problem is limited and additional research in this area is essential. PMID- 2224754 TI - Use of sulfonylurea agents in older diabetic patients. AB - The elderly patient with type II diabetes should be treated in much the same fashion as a younger person with the same disease, although emphasis needs to be placed on minimizing side effects, drug interactions, and hypoglycemia. Chlorpropamide should not be used in these patients, unless there is no other choice. The remaining agents--tolbutamide, acetohexamide, tolazamide, glyburide, and glipizide--should be started at low doses and gradually increased until optimal diabetic control is reached. The initial treatment goal is a FPG level of less than 180 mg/dl and a final goal is a 1- to 2-hour PPG concentration between 140 and 180 mg/dl. The glycosylated hemoglobin value should be no greater than 1.5% above the upper limit of normal, and should be lower, if possible. It must be kept in mind, however, that the closer diabetic patients are to achieving euglycemia, the more likely is hypoglycemia. Treatment goals therefore may have to be relaxed in someone at increased risk of hypoglycemia (e.g., patients with irregular eating habits or renal insufficiency) or when hypoglycemia may pose a greater hazard (e.g., patients with coronary artery or cerebral vascular disease). Patients on sulfonylurea agents should have blood glucose values measured once a month and glycosylated hemoglobin levels determined once every 3 months to alert the clinician to the possible need to adjust therapy. In this way, potential hypoglycemia can be avoided if blood glucose levels are drifting too low and chronic hyperglycemia can be identified and treated within a short period of time. When a patient's status changes--e.g., he is placed on new medication, becomes depressed and anorexic, or develops another medical problem- care must be taken to re-evaluate his diabetes management. Drugs such as sulfonamide antibiotics can potentiate the action of the sulfonylureas and cause hypoglycemia, renal insufficiency may necessitate changing the type of sulfonylurea agent or decreasing the dose, and malnutrition may obviate any need for therapy with an oral hypoglycemic agent. If these guidelines are kept in mind, the older diabetic patient can be managed on a sulfonylurea agent in conjunction with the appropriate diet. Should these measures prove to be ineffective, then insulin therapy should be instituted. Controlling chronic hyperglycemia will help improve the quality of life for patients with diabetes and decrease the probability of developing some of the devastating complications associated with this disease. PMID- 2224755 TI - Insulin treatment in the elderly diabetic patient. AB - Type II diabetes mellitus may affect as many as 20% of the elderly US population. In the absence of data to support the need to maintain a specific level of glucose beyond that necessary to relieve symptoms, choice of therapy is problematic. Clearly, supervised dietary therapy for the obese type II diabetic patient represents a safe and cost-effective treatment. For those patients who fail dietary therapy because they fail to lose weight or regain lost weight, or because blood glucose levels remain high despite weight loss, further therapy must be individualized. The only rational criteria for drug treatment supportable by currently available data are (1) persistent symptoms associated with hyperglycemia, (2) ketonuria in the unstressed state, and (3) certain cases of hyperlipidemia, especially with triglyceride levels greater than 1000 mg/dl. In these clinical settings, drug therapy is necessary to eliminate symptoms, prevent development of ketoacidosis, and reduce the risk of pancreatitis, respectively. Consideration of drug therapy should also be made in the case of very elevated blood glucose levels, even in the absence of symptoms, when dehydration and risk of severe hyperosmolarity exist. The issues regarding insulin versus sulfonylureas have not been examined specifically in the elderly population. Extrapolating from published studies that generally include patients older than 65 years leads to the following conclusions: Caution regarding adverse side effects of insulin (hypoglycemia, theoretic risk of hyperinsulinemia) and sulfonylureas (hypoglycemia, drug interactions, increased risk of cardiovascular death) must be balanced against the theoretic benefit of treatment in the absence of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224756 TI - Glycemic control in elderly people with diabetes. AB - Hyperglycemia is only one of several metabolic derangements that are prevalent in diabetes mellitus. Of these, hyperlipidemia, obesity, and co-existent hypertension may make more important contributions to complications than persistently elevated blood sugars. The role of hyperglycemia in the genesis of diabetic complications is uncertain and there is little evidence from prospective randomized controlled studies to support rigorous hypoglycemic treatment. Adverse consequences of pharmacologic therapy can be severe, including death, and are most frequent in the elderly. The group of elderly diabetic ambulatory patients is markedly heterogeneous and individualization of therapy is required. Obese persons require dietary therapy, and additional dietary manipulations are needed for patients with the complications of hyperlipidemia, hypertension, and nephropathy. Pharmacologic hypoglycemic therapy may be required to control symptoms, but its use in asymptomatic diabetic persons is for the most part unwarranted. PMID- 2224757 TI - Home care of the elderly diabetic patient. AB - As the anticipated growth of sophisticated diabetic services continues to accelerated in homes across America, physicians must first be educated as to the potentially unlimited spectrum of diabetic home care products and services that will become increasingly available to the patients whom they serve. Second, much research must be completed to critically examine the safety, quality, and cost issues of diabetic home care, to provide the necessary data to assure that home care services will be neither under- or over-utilized and will meet the necessary acute and long-term health care needs of our diabetic patients. Third, physicians must take a leadership role in examining the pitfalls of our existing expensive and often fragmented acute care-oriented health care model, which has not effectively addressed the increasing costs and incidence of chronic diseases, such as diabetes, in our society. With computerization and the explosive mobilization of high-technology health care products and services, we are witnessing an exponential growth in the list of services available in the home setting for diabetic patients. There has never been a time in the history of medicine that we, as physicians, have needed to create new, innovative, high quality approaches to necessary, accessible, and cost-effective alternative health care delivery systems as is the case now. I believe that the renewal of home care, with physician vision, direction, and review, will be a major step toward the highest-quality medical care provided to our diabetic patients at home. PMID- 2224759 TI - A phase I study of a new cisplatin derivative for hematologic malignancies. AB - DWA2114R (DWA) is a new derivative of platin compounds that is currently being used in Phase II studies of solid tumors in Japan. The dose-limiting factor is myelotoxicity with mild extramedullary toxicity. This Phase I study consisted of adult patients with relapsed hematologic malignancies. Eight patients received a total of 15 treatment courses of DWA. The starting dose was 800 mg/m2 over 24 hours by continuous infusion. The dose was first increased to 1200 mg/m2 and then to 1600 mg/m2. Clinical toxicity and urinary excretion studies of DWA suggested that 1200 mg/m2/d for successive days would be the best type of administration. When 1200 mg/m2/d was given for 5 days, Grade 2 to 3 diarrhea and nausea and vomiting were encountered requiring parenteral fluids and nutritional support. This suggested that the dose-limiting factor with this schedule was gastrointestinal toxicity. Myelotoxicity was severe, as expected, but tolerable. One of the five patients with acute nonlymphocytic leukemia (ANLL) entered into complete remission and one patient with chronic myelogenous leukemia (CML) in crisis returned to the chronic phase. A Phase II trial of DWA is warranted for hematologic malignancies, especially in myeloid diseases. PMID- 2224760 TI - Toxicity of high-dose cytosine arabinoside in the treatment of advanced childhood tumors resistant to conventional therapy. A Pediatric Oncology Group study. AB - Experience with high-dose cytosine arabinoside (HDAC) in pediatric solid tumors is limited. Sixteen children with solid tumors resistant to conventional therapies were registered in a pilot Pediatric Oncology Group (POG) study that required the administration of HDAC at 3 g/m2 every 12 hours for four doses. There were four cases of rhabdomyosarcoma, two cases of fibrosarcoma, four cases of neuroblastoma, and one case each of germ cell tumor, Wilm's tumor, retinoblastoma, hepatocellular carcinoma, Ewing's sarcoma, and Burkitt's lymphoma. All eligible patients had advanced diseases and had previously received extensive chemotherapy. Thirteen patients received one course of HDAC and three patients received two courses of HDAC. Due to prior treatments, patients had less than normal marrow reserves. Short-term toxicity included nausea, vomiting, suppression of hemopoiesis, drug fever, and increased blood urea nitrogen (BUN), creatinine, and liver enzymes. All evaluable patients recovered from their toxicities. There were no drug-related deaths. None of the patients had neurologic problems, including the only patient with prior irradiation to the skull. With the above schedule, HDAC appears to have manageable toxicity. PMID- 2224758 TI - Economic impact of diabetes mellitus in the elderly. AB - Diabetes mellitus is a prevalent disease in Americans aged 65 years and older. It leads to significant morbidity, mortality, and utilization of health care services. Using extant data, we estimated that health care services provided to elderly persons with diabetes cost $5.16 billion annually, nearly 80% of which were attributed to hospital costs. Treatment for cardiovascular disease as a complication of diabetes accounted for the largest proportion of these costs. In addition to admissions for uncomplicated diabetes, substantial portions of inpatient costs were attributed to renal and neurologic diseases. Expenditures per capita for medical care were 50% higher in the elderly diabetic population than in an elderly nondiabetic population. The average yearly expenditure per diabetic patient was estimated to be $4265, $900 of which were out-of-pocket expenses. We conclude that increased vigilance to prevent or delay the incidence of morbidity leading to hospital admissions must take priority in caring for patients with DM. Intensifying outpatient care may offer the opportunity to accomplish this goal. PMID- 2224762 TI - A phase I study of 4'-0-tetrahydropyranyladriamycin. Clinical pharmacology and pharmacokinetics. AB - A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks. PMID- 2224761 TI - Primary chemotherapy with or without radiation therapy and/or surgery for children with localized sarcoma of the bladder, prostate, vagina, uterus, and cervix. A comparison of the results in Intergroup Rhabdomyosarcoma Studies I and II. AB - A major objective of the second Intergroup Rhabdomyosarcoma Study (IRS-II) (1978 to 1984) was to preserve the bladder without compromising the survival of children with localized genitourinary sarcomas arising in or near the bladder. After incisional biopsy, 109 patients with localized, gross residual sarcoma of the prostate (43 patients), bladder (43 patients), vagina (20 patients), or cervix/uterine corpus (3 patients) were treated with vincristine, dactinomycin, and cyclophosphamide (VAC). After two to four drug courses, radiation therapy and/or surgery were used to treat patients with residual or recurrent tumor. The 3-year survival rate of patients treated on this primary chemotherapy regimen (70%) was similar to that of the primary surgery regimens of IRS-I (78%; P = 0.46), but the 3-year disease-free survival rate was significantly inferior (52% versus 70%; P = 0.02). Since the IRS-II encouraged bladder preservation at the onset of therapy, the percentage of patients with bladder and prostate tumors who retained the bladder was initially substantially higher in IRS-II (97%) than in IRS-I (58%). However, the percentages of 95 patients with bladder-prostate (BP) tumors in IRS-II who retained the bladder and were alive at 2 and 3 years after starting treatment were only 33% and 22%, respectively, compared with 26% and 23%, respectively, in the 66 patients with BP tumors in IRS-I. Thus, sequential treatment with primary chemotherapy, followed by radiation therapy and/or surgery as given in IRS-II, failed to improve the eventual bladder salvage rate. PMID- 2224763 TI - Testicular relapse in children with acute nonlymphoblastic leukemia. AB - The clinical course and other distinctive features of five children who developed a testicular relapse 4 months to 25 months after the diagnosis of acute nonlymphoblastic leukemia (ANLL) are described. The chief presenting feature at relapse was painless testicular enlargement, as is also seen in children with acute lymphoblastic leukemia who relapse in the testes. By French-American British convention, the malignant cells were classified as M4 (myelomonoblastic) in four cases and M2 (myeloblastic) in one. All children received a course of multiagent reinduction chemotherapy and all but one received local irradiation to the testes. Only one of these children, whose relapse was a late event after elective cessation of therapy, is a long-term survivor. A comparison with six previously published cases shows similar clinical characteristics and outcome. Given the poor responses of such patients to conventional treatment, it seems worthwhile to consider the use of intensive reinduction chemotherapy with concomitant bilateral testicular irradiation followed by remission intensification and an autologous or allogenic marrow transplant. PMID- 2224765 TI - Surgical treatment of brain metastases in malignant melanoma. AB - The authors report the results of a retrospective review of 13 patients who underwent 19 craniotomies for resection of metastatic malignant melanoma at the University of Colorado (Denver, CO) between 1983 and 1989. There was preoperative evidence of extracranial disease in 11 patients. Eight patients had more than one intracranial metastasis at operation. Intraoperative ultrasound was used in 18 of the 19 craniotomies to minimize surgical trauma to the brain. The 30-day mortality was zero. The 30-day morbidity was minimal. No patient acquired a new neurologic deficit as a result of surgery. All patients regained at least their preoperative level of functioning. Six of the patients who were living at the time of review have been followed for 4 to 25 months (median, 7.5 months). The seven patients who were dead at the time of review survived 4 to 18 months (median, 10 months). These results compare favorably with the survival of untreated patients with metastatic melanoma to the brain (median, 1 month), patients treated with radiation therapy alone (median, 2-4 months), and those treated with chemotherapy alone (median, 2-4 months). The excision of metastatic melanoma from the brain, although not curative, may increase survival in patients with this problem with little morbidity and mortality even in the presence of other metastases. PMID- 2224764 TI - Structural and ultrastructural study of the ovary in childhood leukemia after successful treatment. AB - Ovarian biopsy specimens from ten girls (three postmenarcheal) who had undergone antiblastic treatment for acute lymphoblastic leukemia (ALL) and were in complete remission were examined by light microscope. The biopsy specimens from four of these patients (three postmenarcheal) were also observed by electron microscope. The structural and ultrastructural analysis showed a reduction in the number of follicles which were otherwise normal. No follicles were found in the thin sections from two of the three postmenarcheal girls, whereas normal follicles were observed in the third. The cortical stroma showed moderate to severe signs of fibrosis and changes of capillaries. All of these alterations were more evident in patients where ALL was diagnosed at an older age and this finding suggests that they are at a higher risk for low fertility or early menopause. PMID- 2224766 TI - Expression of major histocompatibility complex class II antigens and interleukin 1 by epithelial cells of Warthin's tumor. AB - The immunoreactivity for class II antigens of the major histocompatibility complex and interleukin-1 (IL-1) in Warthin's tumor (WT) cells was studied. In addition to macrophages, dendritic cells, and capillary endothelia, the luminal tumor cells and some keratinocytes in the metaplastic squamous foci exhibited immunoreactivity for both class II antigens and IL-1. The distribution of the class II antigens in the luminal tumor cells was limited to their basolateral membrane. These data, together with previous findings, strongly suggest that the luminal tumor cells of WT introduce the luminal antigen to the underlying lymphoid tissue and, thus, act as an antigen-presenting cell. PMID- 2224767 TI - Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas. AB - Membrane-bound carbohydrates may influence the metastatic behavior of cancer cells. Forty-two squamous cell carcinomas (SCC) of the buccal and maxillary alveolar mucosa were studied retrospectively using a monoclonal antibody (BE2) that reacts with blood group H (type 2 chain) structure and an immunoperoxidase (avidin-biotin peroxidase complex) staining technique. H-antigen staining within the entire tumor did not correlate with the stage of the tumor, i.e., tumor spread. However, loss of staining within the most invasive sites of the tumors correlated significantly with the stage of tumor development and histologic grade of malignancy. These findings support the view that features regarding the cells of deeper parts of the carcinomas are very important for the clinical behavior of the tumors and that loss of H-antigen expression is related to the stage of the tumor and invasion of carcinoma cells. PMID- 2224768 TI - Cell lineage markers in human pancreatic cancer. AB - The normal pancreas consists of three major cell types or lineages that share a common embryologic origin from pluripotent endodermal precursors. The type of cell that undergoes neoplastic transformation to form a pancreatic carcinoma is controversial and may influence the phenotype and biologic behavior of the tumor. In this study, immunohistologic techniques were used to determine the cell lineage differentiation expressed in 29 primary exocrine pancreatic adenocarcinomas, five metastatic exocrine pancreatic adenocarcinomas, and five islet cell neoplasma. Specimens of normal pancreas and chronic pancreatitis were used for comparison. The cell lineage markers consisted of monoclonal and polyclonal antibodies against trypsin and lipase (acinar cells); secretory component, carbonic anhydrase II, and pancreatic cancer mucin SPan-1 (ductal cells); and chromogranin-A and somatostatin (islet cells). The expression of carcinoembryonic antigen (CEA) and lysozyme were also determined. This collection of markers allowed the differentiation between acinar, ductal, and islet cells of normal pancreas and chronic pancreatitis specimens. The expression of cell lineage markers in islet cell tumors was homogeneous and restricted to chromogranin-A. In contrast, the expression of these markers in primary and metastatic exocrine pancreatic adenocarcinomas was variable. Reactivity with monoclonal anti-CEA was absent in normal pancreas, and was present in 83% of chronic pancreatitis specimens as well as 90% of exocrine pancreatic adenocarcinomas. In addition, lysozyme reactivity was absent in normal pancreas; however, lysozyme was expressed in one case of chronic pancreatitis, 17 cases of primary carcinoma, and three cases of metastatic carcinoma. These findings support the concept that the original transformed cell type in many pancreatic exocrine carcinomas resemble endodermal "stem cells" that retain the capability of differentiation along more than one cell lineage pathway. PMID- 2224769 TI - Expression of pancreatic secretory trypsin inhibitor gene in human colorectal tumor. AB - Expression of pancreatic secretory trypsin inhibitor (PSTI) gene was examined by Northern blotting analyses in 31 human colorectal tumors that included two benign adenomas and 26 adenocarcinomas. Among the total of 28 cases which proved to be adequate for mRNA analyses, all but one showed the expression of PSTI at various levels. In contrast, PSTI expression was not detected in two malignant lymphomas of the rectum. The level of PSTI expression was not correlated with the patient's age, sex, tumor location or size, stage of differentiation, lymph node metastasis, or progression stage. Some colorectal adenocarcinomas were also shown to express genes that can hybridize with human trypsinogen cDNA probe. It looks as though in these tumors, a protease(s) and its inhibitor are produced simultaneously as part of a cellular self-defense mechanism. PMID- 2224770 TI - An analysis of abnormalities of the retinoblastoma gene in human ovarian and endometrial carcinoma. AB - The altered expression of the human retinoblastoma (RB) gene has been demonstrated to play an important role in the pathogenesis of RB and other tumors. To determine whether the RB gene might be involved in the pathogenesis of human ovarian and endometrial cancer, DNA from 24 human ovarian tumors, 3 normal ovaries, 3 endometrial carcinomas, and 1 endometrial hyperplasia was examined with an RB complementary DNA probe. Evidence for homozygous deletion of the RB gene was observed in only one specimen. Interestingly, the specimen was an endometrioid tumor of the ovary of low malignant potential (LMP). This patient experienced rapid progression of the tumor and died 8 months after diagnosis. Abnormalities of the RB gene may be involved in the aggressive biologic behavior of certain forms of ovarian carcinoma, particularly those of LMP. PMID- 2224771 TI - Distribution of immunoglobulins and secretory component in gastric cancer of the aged. AB - The secretory immune system plays an important role in the local humoral immunity of the gastrointestinal tract. In order to evaluate humoral immunity in gastric cancer, distribution of immunoglobulins (Ig) and secretory component was immunohistochemically studied in 74 early and 15 advanced primary gastric cancers. In non-cancerous gastric mucosa, IgA and IgM, and secretory component were mainly identified in the cytoplasm of the intestinal metaplasia. In early gastric cancer of well-differentiated type, the localization of IgA and IgM, and secretory component was similar to that of intestinal metaplasia. In advanced gastric cancer, they were faintly observed and showed low positivity. The number of Ig-containing cells infiltrating cancerous stroma was enumerated. Immunoglobulin A-containing cells were dominant in the stroma of early gastric cancer. On the other hand, there were few Ig-containing cells in the stroma of advanced gastric cancer, and the number of IgA-containing and IgM-containing cells was also decreased. These results suggest that local humoral immunity is suppressed in gastric cancer, especially in advanced gastric cancer. PMID- 2224772 TI - DNA analysis of multiple synchronous renal cell carcinomas. AB - The authors used retrospective quantitative DNA analysis to study interrelationships between multiple synchronous renal cell carcinomas in seven patients. DNA content was determined by image analysis on Feulgen-stained nuclear smears prepared from multiple paraffin blocks from each tumor. Tumors were unilateral in four cases and bilateral in three. Ten tumors had homogeneous, and four heterogeneous DNA stemlines. Intertumoral heterogeneity in four cases suggested multifocal origin. Identical DNA aneuploid indices in bilateral tumors in one case suggested metastasis from a solitary origin. Abnormal DNA content and heterogeneous populations began to appear in the size range 2.0 to 5.0 cm. All tumors over 5.0 cm contained nondiploid populations. Although the interrelationships between these multiple synchronous neoplasms are not entirely clear, the DNA analysis suggests that the occurrence of nondiploid stemlines and heterogeneous DNA content may parallel both tumor growth and more aggressive behavior. PMID- 2224774 TI - Hyperthermia alone in the treatment of recurrences of malignant tumors. Experience with 60 lesions. AB - Localized hyperthermia alone has been used for the treatment of cancer recurrences in which previous conventional therapies have failed. Since 1983 and 1988, 57 patients with 60 lesions have been heated by means of a microwave and radiofrequency system. Treatment protocol provided 45 minutes of heating at the intratumor temperature of at least 42 degrees C, twice a week, for a total number of six, eight, or ten heating sessions. Invasive intratumor thermometry was performed for all lesions. Complete response (CR) was obtained in ten cases (16.6%) and partial response (PR) in 14 (23.4%). Higher rates of CR were observed in the chest wall (38.5%) compared with the head and neck area (11.4%), trunk (10%), and limbs (none). Adenocarcinoma was the most responsive histologic type (40%). Squamous cells carcinoma had 7.7% CR. The only case of undifferentiated carcinoma showed CR; there were none on five sarcomas. Long-term local control (24 months) was approximately 7%. The multivariate analysis showed the statistical significance of the histologic variety (adenocarcinoma versus others, P less than 0.0001). Side effects and complications of the treatment were minimal. PMID- 2224773 TI - Giant cell tumor of bone. A clinicopathologic and DNA flow cytometric analysis. AB - Flow cytometric DNA analysis was performed on 60 cases of giant cell tumor of bone and the results were correlated with the clinicopathologic features. Tumors studied were from 31 men and 29 women whose ages ranged from 18 to 62 years (median, 29 years). The most common sites were the distal end of the femur and proximal end of the tibia, accounting for 75% of the lesions. Treatment consisted of resection in 29 patients (48%), curettage with bone chip packing in 15 patients (25%), or curettage with cement packing in 16 patients (27%). Ten patients (17%) had local relapse within 1 to 3 years, and two had lung metastases. Forty-two patients (70%) exhibited tumors with a diploid DNA content, 16 aneuploid (27%), and two tetraploid (3%). Six (37.5%) of the aneuploid patients had relapses: one of those had been treated by resection of the tumor and five by curettage. Of the remaining ten (62.5%) unrelapsed aneuploid patients, nine had been treated by resection of the tumor and one by curettage. Four of the 42 diploid patients (9.5%) had relapses; all had been treated by curettage of the tumor. The two tetraploid tumors were treated by resection and none relapsed. Histologic parameters did not correlate with relapse rate or DNA pattern. Although relapse was more common among aneuploid tumors, our study shows that this appears to be influenced by the treatment modality rather than the ploidy status. Based on this study the DNA analysis of giant cell tumor of bone has a limited utility for predicting the tumor's biologic behavior. PMID- 2224775 TI - Time trends in Hodgkin's disease incidence. The role of diagnostic accuracy. AB - A prior study of Hodgkin's disease (HD) incidence using national cancer survey data (1969-1980) identified unprecedented rate declines among white persons older than 40 years, and rate increases among young adults aged 15 through 39. These trends could be due to improved diagnostic accuracy. To investigate this hypothesis, the authors updated incidence rates in whites by age, sex, and histologic subtype through 1984; quantified diagnostic accuracy in corresponding detail using Repository Center for Lymphoma Clinical Studies data, which include original and expert review diagnoses on lymphoma patients; and recalculated HD incidence rates (1969-1984) corrected for diagnostic error. Updated HD incidence rates through 1984 continued to decline in older adults and showed persistent increases for young adults with the nodular sclerosis (NS) histologic subtype. The percentage of original HD diagnoses confirmed on review (confirmation rate) decreased with age and increased over time; in older adults, these patterns opposed observed incidence trends. However, for young adults, confirmation rates of NS, the most common subtype at these ages, were high and changed little over time. After adjustment for diagnostic error, incidence rates for older adults were lower than previously observed and showed no secular changes. However, young adults with NS had slightly larger rate increases than in uncorrected data. Thus, contemporary changes in HD incidence for whites primarily involve growing risk to persons at the start of adult life. These patterns are compatible with trends in suspected sociodemographic risk factors that suggest an infectious etiology for HD. PMID- 2224776 TI - Nasal lymphoma. A retrospective analysis of 60 cases. AB - Sixty cases of nasal lymphomas were reviewed. There were 42 men and 18 women. The median age was 49 years. The histologic types were low grade in four cases, intermediate grade in 33, high grade in seven, and unclassifiable in 16. Thirteen cases had features of polymorphic reticulosis. The immunophenotype was available in 18 cases and a majority of 67% of them were T-cell. Forty-one of them (68%) had clinically localized (Stage I and II) disease which often spread locally to neighboring tissues and they presented predominantly with nasal symptoms. Nasal lymphoma appeared to carry a poor prognosis. Although our patients with clinically localized disease had significantly better prognosis than those with advanced disease, the 5-year survival of Stage I and II patients was only 55%. Chemotherapy did not appear to be more effective than radiotherapy alone in preventing relapses but the patient number was too small to allow a firm conclusion to be made. Patients with advanced disease had even poorer prognosis with a 5-year survival of only 17%. Innovative therapy has to be developed for these patients. PMID- 2224777 TI - Clear cell adenocarcinoma of the lower genital tract. Correlation of mother's recall of diethylstilbestrol history with obstetrical records. AB - The written obstetric records of maternal exposure to diethylstilbestrol (DES) were used as a criterion standard and compared with the DES exposure history recalled by mothers of women with vaginal, cervical, or indeterminable vaginal/exocervical clear cell adenocarcinoma. Among cervical cases, the sensitivity of maternal recall was 50% (N = 2), and its specificity was 100%. Among vaginal and vaginal/exocervical cases, this sensitivity was 72%; specificity was 60%; and the majority of these mothers who said they did not take DES were DES positive by written records. Thus investigators should avoid using maternal recall alone to measure DES exposure. Among subjects for whom written maternal obstetric records were available, 88% of vaginal cases and 46% of cervical cases were DES positive. The authors conclude that few cases of vaginal clear cell adenocarcinoma should occur in young women as the cohort of women exposed in utero to DES continues to age, whereas cases of cervical origin may continue to occur. PMID- 2224778 TI - Multiple spinal metastases from paraganglioma. AB - Isolated vertebral body metastases from paraganglioma are exceedingly rare. They have been reported to occur in the presence of active primary tumor in the neck, local recurrence, or widespread metastases. A unique case of carotid body tumor (paraganglioma) is reported with the following features: (1) multiple vertebral body metastases (C6, T9, and L3) presenting with spinal cord compression, and no evidence of local recurrence or other metastatic disease; (2) absence of mitoses on the original specimen or the metastatic deposit; and (3) a prolonged interval (9 years) to the development of symptomatic metastases. PMID- 2224779 TI - Genetic diagnosis of Lynch syndrome II in an extended colorectal cancer-prone family. AB - Knowledge of colon cancer genetics, with particular attention to precision in hereditary cancer syndrome diagnosis, can often enable highly targeted surveillance and management strategies for patients at high genetic risk. Unfortunately, the patient's family history of cancer is often given minimal attention, and knowledge of hereditary cancer syndromes is frequently limited. Indeed, many physicians still consider familial adenomatous polyposis (FAP) as the only genetic risk factor for colorectal cancer. This concern with FAP was noted in a colorectal cancer-prone kindred which for decades had been thought to manifest that syndrome. However, after meticulous genetic, medical, and pathologic studies, the cardinal phenotypic characteristics of Lynch syndrome II were observed. The potential for cancer control in current and future generations of families like this one clearly mandates the need for computerized registries which could transmit current information about hereditary colon cancer syndrome diagnosis, surveillance, and management. PMID- 2224780 TI - Cancer in the families of children with soft tissue sarcoma. AB - The cancer experience among 754 first-degree relatives (mothers, fathers, and siblings) of a population-based series of 177 children with soft tissue sarcoma is reported. The current study represents an extension of our earlier work in which the authors found an excess of breast cancer in the mothers of 143 of these children. There were 40 cancers among all first-degree relatives, compared with 24.82 expected (relative risk [RR] 1.61, P = 0.006). There was no excess in fathers, but an excess of borderline significance was seen in mothers (RR 1.67, P = 0.0545), and a significant excess in siblings (RR 4.55, P = 0.0002), mainly due to carcinoma of the breast and pediatric tumors. Results of a step forward Cox multivariate analysis identified three variables in the index child which were independently associated with high cancer risk in relatives, as follows: age younger than 24 months at diagnosis; histologic type, embryonal rhabdomyosarcoma or other and unspecified soft tissue sarcoma; and male sex. It was possible, therefore, to identify a subgroup of children whose relatives are at high risk of early onset cancer (RR in this group 10.14). The pattern of cancers is consistent with the Li-Fraumeni syndrome. The authors conclude that a marked proportion of childhood soft tissue sarcoma has a genetic basis. PMID- 2224781 TI - Cholecystectomy and right colon cancer in Puerto Rico. AB - A case-control study was undertaken to evaluate the possible relationship between cholecystectomy and right colon cancer. Two hundred patients with adenocarcinoma of the cecum or ascending colon (diagnosed between 1984 and 1989) were compared with 200 matched neighborhood controls. Cholecystectomy history was obtained through interviews using structured questionnaires and subsequently validated from hospital records. A statistically significant association (odds ratio = 2.14) was found between right colon cancer and a history of prior cholecystectomy. The altered bile metabolism which occurs after removal of the gallbladder may have a carcinogenic effect on the right colon. Dietary habits of the colon cancer patients in our study were consistent with prior reports in the literature, showing that this group has a lower intake of vegetables and cereal fiber than the control population. PMID- 2224782 TI - Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Long-term results of the Radiation Therapy Oncology Group study 81-17. AB - One hundred twenty-four eligible patients with advanced mucosal squamous cell carcinoma of the head and neck were entered into a pilot study of concomitant cisplatin (100 mg/m2 given every 3 weeks for three doses) and standard irradiation. The initial complete response (CR) was 71% with an additional two cases salvaged by surgery for an overall 73% CR. When no keratin was identified in the histologic specimen (41 patients) the CR was 90%. The nasopharynx showed the best CR (89%) among the sites. At 4 years after treatment, the estimated locoregional tumor control rate was 43% and the survival, 34%. When no keratin was present in the specimen, the estimated locoregional control of tumor was superior (56% versus 38% with keratin identified, P = 0.02) and the estimated survival was also superior (48% versus 26%, P = 0.008). Acute treatment-related toxicities included one death due to renal damage and two patients with life threatening renal damage. The delivery of radiotherapy was not altered. Late toxicity included necrosis -3%, fibrosis -4%, and one fistula. The results of this study justify a randomized trial for the comparison of this combination of cisplatin and radiotherapy versus radiotherapy alone in advanced mucosal carcinomas of the head and neck. PMID- 2224783 TI - Final report of the French multicenter phase II study of the nitrosourea fotemustine in 153 evaluable patients with disseminated malignant melanoma including patients with cerebral metastases. AB - One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma. PMID- 2224784 TI - Treatment of advanced neuroblastoma with emphasis on intensive induction chemotherapy. A report from the Study Group of Japan. AB - One hundred nine newly treated patients with advanced neuroblastoma were entered in this study between January 1985 and May 1989. The eligible patients included infants younger than 12 months of age with Stage IVA disease (bone cortex, distant lymph node, and/or remote organ metastases) and patients aged 12 months or older with Stage III or IV disease (IVA plus IVB with tumor crossing the mid line and with metastases confined to bone marrow, liver, and skin). The patients first received six cyclic course of intensive chemotherapy (regimen A1), consisting of cyclophosphamide (1200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (pyrarubicin; 40 mg/m2), and cisplatin (90 mg/m2). Original tumors and the regional lymph node metastases were removed some time during these first six cycles of chemotherapy. The patients were further divided into three groups. Patients in course 1 received alternating treatment by regimen B (cyclophosphamide and ACNU) and intensified regimen A1, and those in course 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in course 3 were treated with bone marrow transplantation (BMT) preceded by high-dose preconditioning chemotherapy. Survival rates were 77% in Stage III and 54% in Stage IV at 2 years, and 70% in Stage III and 45% in Stage IV at 3 years. The major toxicities encountered were bone marrow suppression with leukocyte counts down to 100/mm3, mild cystitis, and hearing impairment. The 2-year survival rate was 78% in 21 patients who underwent BMT when complete remission was achieved. We concluded that our intensive induction chemotherapy is of significant value in increasing the rate of complete response, and in widening the indications for and achieving improved results of treatment with BMT. PMID- 2224785 TI - Toxic dermatitis induced by 10-ethyl-10-deaza-aminopterin (10-EdAM), a novel antifolate. AB - A new methotrexate analog, 10-ethyl-10-deaza-aminopterin (10-EdAM), was found to induce a particular form of skin toxicity different than the skin rash reported to result from methotrexate. At histologic examination, it was found to be a toxic dermatitis that clinically most often first appears on the lower legs but can occur anywhere in the body, especially if treatment is continued. Nine cases are reported. A specific risk factor could not yet be identified. Discontinuation of 10-EdAM administration leads to complete healing; concomitant corticosteroid treatment also induces healing. PMID- 2224786 TI - Chemotherapy-related hemolytic-uremic syndrome after the treatment of head and neck cancer. A case report. AB - A 62-year-old woman who was being treated for squamous cell carcinoma of the head and neck developed a chemotherapy-related hemolytic-uremic syndrome during the second cycle of neoadjuvant chemotherapy consisting of cisplatin, bleomycin, and methotrexate. Though the syndrome was suspected early, attempts at reversing the hematologic and renal abnormalities were unsuccessful. At postmortem examination, the characteristic microvascular lesions of the hemolytic-uremic syndrome were found in the kidneys. PMID- 2224787 TI - Primary carcinoma of the upper urinary tract. Effect of primary and secondary therapy on survival. AB - The pathologic material and medical records of 76 patients with primary upper urinary tract carcinomas were reviewed to identify the role of grade and stage in predicting survival; to determine any differences in survival between ureteral and renal pelvic carcinoma; to understand the role of local therapy in low grade, low stage tumors; and to establish the usefulness of adjuvant therapies in metastatic disease. Kaplan-Meier survival curves with Cox-Mantel analysis for statistical significance revealed both grade and stage to be excellent predictors of survival. No differences in survival were noted between renal pelvic and ureteral carcinomas for equivalent stage tumors. For low grade, low stage tumors, although there was an increased risk of local recurrence with local therapy, there were no differences in survival between patients treated with local therapy or radical surgery. Finally, cisplatin-based chemotherapy seemed to improve survival in patients with metastatic disease. PMID- 2224788 TI - Osteosarcoma of the maxilla in Hong Kong Chinese postirradiation for nasopharyngeal carcinoma. A report of four cases. AB - Postirradiation osteosarcoma of the maxilla was seen in four Hong Kong Chinese patients treated for nasopharyngeal carcinoma. These cases represent four of 42 (9%) cases of osteosarcoma at all sites in this institution during the period 1979 to 1989, when more than 1000 patients were treated with radiotherapy for nasopharyngeal carcinoma. The latent periods varied from 8 to 11 years from completion of radiotherapy treatment to development of osteosarcoma. The radiation dosage varied from 6000 to 6280 cGy in three of the patients. These cases fit the criteria for diagnosis of postirradiation sarcomas. Maxillary osteosarcomas after irradiation for nasopharyngeal carcinoma do not appear to have been described. The very high incidence of nasopharyngeal carcinoma (for which radiotherapy is the treatment of choice) in Hong Kong Chinese would make the occurrence of such tumors more likely in Hong Kong, although the small risk does not contraindicate the use of radiation in the treatment of nasopharyngeal carcinoma in view of its well-documented efficacy. PMID- 2224789 TI - Perinatal infection of human T-lymphotropic virus type I, the etiologic virus of adult T-cell leukemia/lymphoma. DNA amplification of specific human T lymphotropic virus type I sequences. AB - A gene amplification technique, polymerase chain reaction, was used to detect human T-lymphotropic virus type I (HTLV-I), the etiologic agent of adult T-cell leukemia/lymphoma, in mononuclear cells in peripheral blood and breast milk of ten HTLV-I carrier gravida. The DNA in umbilical cord blood mononuclear cells of the neonates born to the HTLV-I carrier gravida were also amplified and examined for the possibility of HTLV-I infection via placenta during pregnancy. The HTLV-I sequences were detected both in the peripheral blood and milk of all ten carrier gravida by Southern blot analysis of amplified DNA. However, HTLV-I proviral DNA could not be detected in the cord blood of the carriers' neonates, indicating that transplacental infection of HTLV-I should be rare and that postpartum infection via breast milk is a likely major perinatal transmission route. PMID- 2224790 TI - Immune deficiency in family members of patients with Hodgkin's disease. AB - Indirect data supporting a preexisting immunologic impairment in patients with Hodgkin's disease (HD) have been presented in recent years. These immunologic defects are supposed to be related to genetic and/or environmental factors. In this study, 65 first-degree relatives and 12 spouses of 21 consecutive patients with HD were studied immunologically. Furthermore, seven twin pairs in which one partner had HD and four additional nonmatched healthy co-twins were also included in the study. A decreased lymphocyte DNA synthesis induced by Concanavalin A, a high spontaneous DNA synthesis, or a low CD4+/8+ ratio was found in 21 (32%) consanguineous, two (17%) nonconsanguineous relatives, and five (50%) healthy co twins. The corresponding figures for the untreated patients with HD and the control series were 14 of 21 (65%) and 21 of 127 (16%), respectively. Total lymphocyte counts or lymphocyte subpopulations did not differ between HD relatives and controls. The increased frequency of blood lymphocyte defects among consanguineous first-degree relatives favors the existence of a genetically determined immune deficiency in at least a proportion of apparently healthy relatives of patients with HD. However, nongenetic factors such as age and environment may add to the defect. PMID- 2224791 TI - Impaired production of tumor necrosis factor in breast cancer. AB - Spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF) by peripheral blood macrophages was investigated in breast cancer. Whereas spontaneous TNF production by macrophages derived from patients with breast cancer was comparable with the one found in healthy controls (P greater than 0.1), LPS-stimulated macrophages derived from patients in the disease-free interval as well as with metastatic breast cancer were found to produce significantly lower amounts of TNF, as compared with macrophages derived from healthy control individuals (P less than 0.0005). However, the production of TNF did not significantly differ between the two patient populations (P greater than 0.05). The impairment of LPS-induced TNF production did not depend upon such characteristics of the primary tumor as size, axillary lymph node and estrogen receptor status, or upon the fact of administration of adjuvant chemotherapy and, in patients with metastatic disease, hormone treatment. To further investigate cytokine production by macrophages, spontaneous and LPS-induced interleukin-1 (IL 1) production was investigated also. However, no difference was found between patients and controls concerning IL-1 generation. The authors thus conclude that LPS-induced TNF production was impaired in breast cancer independent of the presence of detectable metastatic disease, whereas IL-1 production remained unimpaired. PMID- 2224792 TI - Possible involvement of the retinoblastoma gene in undifferentiated sinonasal carcinoma. AB - Retinoblastoma tumor formation is initiated by the loss of function of both alleles of the RB-1 gene on chromosome 13. Patients with the hereditary form of retinoblastoma carry a germ line mutation at one of the two homologous gene loci in all cells and have an increased risk for nonocular tumors (mainly osteosarcoma and other mesenchymal tumors) in later life. The authors studied a 38-year-old patient with sinonasal undifferentiated carcinoma (SNUC) who had been treated for bilateral retinoblastoma by enucleation (left eye) and irradiation (right eye), respectively. Using molecular probes for the RB-1 gene and other loci on chromosome 13, the authors detected a deletion at the RB-1 locus in metastatic SNUC cells that was not present in normal tissue. These findings indicate that somatic mutations at RB-1 locus may be involved in the formation or progression of ectodermal tumors. PMID- 2224793 TI - Sialosyl-Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients. AB - Colon cancers typically produce mucin. However, it is not known whether tumor mucin plays a biological role in cancer cell behavior. To address this issue, the expression of a mucin-associated antigen, sialosyl-Tn, was examined by immunohistochemical study in 128 primary colorectal carcinoma specimens from 137 patients who underwent curative surgical resection. Antigen expression was correlated with disease-free and overall 5-year survival. Sialosyl-Tn antigen expression occurred in 112 (87.5%) tumors, and was independent of age, gender, tumor location, Dukes' stage, depth of invasion, degree of differentiation, and ploidy status. Survival at 5 years for patients with sialosyl-Tn-negative versus sialosyl-Tn-positive tumors was 100% versus 73% (P less than 0.05) and disease free survival was 94% versus 73%, respectively (P = 0.12). Although more advanced Dukes' stage, deeper invasion, and aneuploidy were all associated with poorer overall 5-year survival, antigen-negative tumors within each of these groups had much better prognoses than antigen-positive tumors. Multivariate regression analysis revealed that tumor ploidy (P less than 0.001) and sialosyl-Tn expression (P less than 0.05) were the two variables of most importance for predicting both disease-free and overall survival. The authors conclude that sialosyl-Tn expression is an independent predictor of poor prognosis in colon cancer, and therefore suggest that qualitative mucin alterations may reflect important differences in the biological behavior of these neoplasms. PMID- 2224794 TI - Characterization of epidermal growth factor receptor in normal and neoplastic human endometrium. AB - Growth factors, including epidermal growth factor (EGF), have been implicated in the growth of several types of cancer. This study compares EGF receptors in normal and neoplastic endometrium. Membrane fractions were isolated from surgical specimens. Radioreceptor assays demonstrated the presence of receptors with a dissociation constant of 0.64 nmol/l in normal endometrium. Affinity cross linking revealed receptor molecular weight of 150 to 170 kiloDaltons (KD). A survey of samples (n = 37) revealed progressive decrease of EGF receptors in cancers of increasing grade: Grade 1-2 adenocarcinoma decreased 34% from control (n = 6, P less than 0.01), whereas Grade 3 adenocarcinoma decreased 90% (n = 7, P less than 0.01) and sarcoma decreased by 72% (n = 3, P less than 0.01). The dissociation constant and molecular weight of the receptor in neoplastic endometrium did not differ significantly from normal. The inverse relationship with grade suggests receptor alteration or down regulation by hormones and/or growth factors. PMID- 2224796 TI - Increased expression of the multidrug-resistance gene in undifferentiated sarcoma. AB - We analyzed multidrug-resistance gene (mdr1 gene) expression in a patient with undifferentiated sarcoma of the liver using the cloned cDNA for the mdr1 gene. Tissue samples were available at the time of initial diagnosis and of two intracranial relapses after chemotherapy with a regimen including doxorubicin and teniposide. The level of mdr1 gene expression was increased sevenfold in the intracranial tumor at the time of first relapse and 11-fold at the second relapse. This case may be an example of acquired multidrug resistance associated with overexpression of the mdr1 gene. PMID- 2224795 TI - Parathyroid hormone-like peptide in normal and neoplastic mesothelial cells. AB - Mesothelioma has not been commonly reported as a cause of hypercalcemia of malignancy. We have studied a patient with malignant mesothelioma and hypercalcemia in association with elevated plasma concentrations of parathyroid hormone-like peptide (PLP). Immunohistochemical analysis of the tumor and seven of eight other mesotheliomas that were not associated with hypercalcemia revealed the presence of PLP cytoplasmic immunopositivity. PLP immunopositivity was also detected in normal and reactive mesothelial cells. The results of these studies suggest that PLP immunoreactivity is common in normal and neoplastic mesothelial cells and raises the possibility that PLP production may play a role in the pathogenesis of hypercalcemia associated with mesothelioma. PMID- 2224797 TI - Non-Hodgkin's lymphoma in the elderly. I. Pathologic features at presentation. AB - The pathologic findings of 118 patients aged 70 years or older with non-Hodgkin's lymphoma (NHL) are reported. These patients formed 27.2% of 433 consecutive cases of NHL seen in a single institution over a 5-year period. Thirty-one of 433 NHL cases were histologically not classified, whereas the remaining 402 could be classified according to the International Working Formulation (WF) of NHL for clinical usage. Immunophenotypic analyses were carried out in 112 NHL cases; of this group 28 were NHL in elderly patients. Of the 95 elderly NHL that could be classified in the histologic categories of the WF 28 cases were in the low-grade, 41 in the intermediate-grade, and 26 in the high-grade categories. Eighty-one cases had diffuse histologic types and 14 had follicular/nodular histologic types. Thirty-five cases were of the G (diffuse large cell) + H (large cell, immunoblastic) categories. No significant differences in the prevalence of the different subtypes were observed among patients younger or older than 70 years. Immunohistologically, most NHL cases in the elderly expressed B-cell phenotype. Sixty-two NHL in the elderly were extranodal at presentation. The results of this study indicate that elderly patients form a relevant proportion of patients developing NHL and thereby present a very difficult management problem. The pathologic features of NHL in the elderly does not differ significantly from those of their younger counterparts, although an increase in diffuse versus follicular histologic patterns, and in extranodal versus nodal disease was observed with advancing age. PMID- 2224798 TI - Diffuse intermediate lymphocytic lymphoma. A clinicopathologic study and comparison with small lymphocytic lymphoma and diffuse small cleaved cell lymphoma. AB - Controversy has recently arisen as to whether diffuse intermediate lymphocytic lymphoma (ILL) should be considered a low-grade or an intermediate-grade non Hodgkin's lymphoma for clinical purposes. Therefore, the authors performed a clinicopathologic study to determine the biologic course of diffuse ILL (40 cases) and compared it with small lymphocytic lymphoma (SLL; 51 cases) and diffuse small cleaved cell lymphoma (DSCCL; 14 cases). They found that patients with diffuse ILL having pseudofollicular proliferation centers (PC) had a significantly longer median survival (84 months) than those without PC (46.5 months; P = 0.03). The median survival of patients with SLL was 72 months, whereas those with DSCCL had a median survival of only 18 months. Based on these findings, the authors conclude that diffuse ILL with PC should be included in the low-grade category of SLL for clinical purposes, whereas diffuse ILL without PC (true diffuse ILL) should be considered an intermediate-grade non-Hodgkin's lymphoma. True diffuse ILL is similar to centrocytic lymphoma in the Kiel classification and should be accorded a similar status in a modified Working Formulation. PMID- 2224799 TI - Cerebral tumor staging in patients with bronchial carcinoma by computed tomography. AB - Computerized tomographic (CT) scans of 271 patients with histologically proven bronchial carcinoma accomplished for initial tumor staging were retrospectively evaluated for signs of cerebral metastasis. The results for the histologic subtypes were quite different. In 13.8% of patients with small cell carcinoma and limited disease the authors found signs of brain metastasis. However, routine cerebral staging in these patients did not seem to be useful because of lack of therapeutic consequences. On the other hand, no patient with non-small cell carcinoma (N-SCC) and tumor Stage I or II had brain metastases. All patients with brain metastasis from N-SCC had been classified as tumor Stage III before cerebral imaging. Among these patients, however, the authors found brain metastasis in 17.5% of those without known distant metastatic disease (III/M0), especially in large cell carcinoma and in adenocarcinoma. Stage III/M0 patients should undergo routine cerebral imaging if their tumor is surgically resectable and thoracotomy is planned. PMID- 2224800 TI - Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer. AB - The infiltration of dendritic cells determined in 210 patients with gastric carcinoma was investigated from the standpoint of tumor invasion, lymph node metastasis, and prognosis. Dendritic cell infiltration was graded as "slight" and "marked." The 39% frequency in the marked infiltration group at the mucosal stage did not change in proportion to invasion into the deeper layers. The 5-year survival rate was 60.4% in patients with marked infiltration and 38.8% in those with slight infiltration, which was statistically different (P less than 0.01). The difference in survival rates was only statistically significant in those with cancer emerging from the serosa (P less than 0.001). There was a similar incidence of lymph node metastasis between the marked and slight infiltration groups in each grade of tumor invasion. However, marked infiltration of dendritic cells prevented widespread nodal involvement beyond the primary node in cases of advanced carcinoma (P less than 0.05). These findings indicate that infiltrating dendritic cells do not prevent the spread of tumor invasion but do prevent nodal involvement; therefore, for patients with a gastric cancer emerging from the serosa, the prognosis will be good. PMID- 2224801 TI - Thromboembolism. A complication of weekly chemotherapy in the treatment of non Hodgkin's lymphoma. AB - In a retrospective survey of 85 patients who received chemotherapy as treatment for non-Hodgkin's lymphomas, the authors found that clinically apparent thromboembolic disorders occurred in four of 11 patients receiving weekly chemotherapy, and in none of 74 patients who were treated on less intensive schedules, suggesting that intensive weekly chemotherapy is thrombogenic. The possible mechanisms of this effect are discussed. PMID- 2224802 TI - Predicting distant metastases in operable breast cancer patients. AB - Risk factors for distant metastases following mastectomy and axillary node dissection for breast cancer were analyzed in a review of 1022 women. From diagnosis until the end of the adjuvant treatment, six stages were identified that corresponded well to patient data acquisition. At each stage, a prognosis study based on the Cox model was carried out using all acquired information from the first stage. The results demonstrated that tumor size, nuclear pleomorphism, mitotic index, and nodal status at the top of axilla were stable independent risk factors in predicting metastasis-free survival (MFS). These analyses also revealed those factors that were significantly related to MFS at one or several stages and losing their significance at a subsequent stage. This was the case with clinical node status, age, and vascular tumor emboli. Other factors such as estrogen, progesterone, histologic grade, and clinical stage were never identified as independent factors at any stage. The four major stable risk factors were used to define a stratification of reference. The results demonstrated that the mere knowledge of clinical information such as tumor size, clinical node status, and age would enable 51% of the patients to be universally well classified according to that stratification. Knowledge of additional factors, such as nuclear pleomorphism and mitotic index, would bring the rate up to 61%, and then to 64% if supplementary information such as vascular tumor emboli were acquired. These percentages did not appear high enough to claim that the physician may make a reliable prognosis of operable breast cancer patients before acquiring information from the axillary node dissection. However, it was proven that there exist some subsets of patients with stable prognosis, i.e., subsets of patients who will belong permanently to the same risk group through the stages. PMID- 2224803 TI - Familial testicular cancer in five members of a cancer-prone kindred. AB - Of a family of 13 siblings, four brothers have developed testicular neoplasms, one embryonal cell carcinoma and three testicular seminomas. A first cousin once removed on their mother's side of the family (fourth-degree relative) has developed an embryonal carcinoma. After treatment they are all alive and well. Their mother is a dizygous twin and one of ten siblings. Multiple other cancers have been diagnosed among her siblings and their offspring including breast carcinoma at age 30 years in monozygous twin nieces. Associated urogenital abnormalities, concordance of age, and discordance of pathology in the five males with testicular cancer is discussed. Further identification and reporting of this risk factor is encouraged. PMID- 2224804 TI - Familial occurrence of gastric cancer in the 2-year experience of a population based registry. AB - The authors studied the familial occurrence of tumors in 154 individuals with gastric cancer by reviewing the clinical data and the genealogical tree of all patients registered in 1986 through 1987 in the Local Health Care District of Modena, Italy, for cancer of the stomach. Crude and age-adjusted (world population) incidence rates of gastric cancer were 34.0 and 21.4 new cases/100,000/year, respectively, in men, and 24.5 and 10.9 in women, respectively. Among first-degree relatives of the registered patients there were 30 cases of gastric carcinoma versus 15 cases in a control group matched for age and sex (Mantel-Haenszel odds ratio [M-H OR] 3.14, P less than 0.01). This excess of gastric neoplasms was observed in siblings (17 versus 7, M-H OR 4.33, P less than 0.02) but not in parents (13 versus 8, not significant). Besides gastric cancer, there was no significant excess of other type of tumors in case families. The familial occurrence of gastric cancer tended to be more frequent in patients with "diffuse" carcinoma (52%) than in subjects with "intestinal" cancer (33%), although the difference was not statistically significant. In conclusion, the current investigation suggests that a "family history" for gastric neoplasms is usually observed in approximately 10% to 15% of the registered cases. As already described for other common malignancies, therefore, the familial occurrence of gastric carcinoma suggests the existence of a genetic susceptibility to cancer of the stomach, at least in a fraction of these patients. PMID- 2224805 TI - Common ground. PMID- 2224807 TI - Self-esteem: a problem for nurses. PMID- 2224806 TI - Excellence. PMID- 2224808 TI - A celebration of love and care. PMID- 2224809 TI - Technology for health care education. PMID- 2224810 TI - Recombinant human erythropoietin. PMID- 2224811 TI - Tough times, are we ready? PMID- 2224812 TI - The special care unit. PMID- 2224813 TI - [Subcutaneous analgesic administration]. AB - In March 1989, Saint Luke's Hospital in Montreal piloted the use of continuous and intermittent subcutaneous injection of analgesics. This practice involved patients whose pain could not be relieved by traditional methods of analgesic administration. The article describes the positive results of the project, and clearly identifies suitable patients. It also outlines the advantages, limiting factors and risks involved with each type of infusion. Procedures for set-up and monitoring are briefly explained. The authors conclude that family members of patients can be easily taught to perform the procedure at home. PMID- 2224815 TI - Forgetting MHAs. PMID- 2224814 TI - [Nursing research and you]. AB - In this article the author shows how important it is for nurses at all levels of the profession to get involved in nursing research. She highlights the advantages of research, in terms of job satisfaction and quality care. The article answers the five most frequently asked questions: What is nursing research? What purpose does it serve? How is it carried out? What role does the health care provider play? What are the benefits? PMID- 2224816 TI - Fighting AIDS abroad. PMID- 2224817 TI - Caring for patients with AIDS. PMID- 2224818 TI - The sleeping giant awakes. PMID- 2224819 TI - Managing decubitus ulcers. PMID- 2224821 TI - When a nurse dies. PMID- 2224820 TI - Values in maternal and newborn care. PMID- 2224822 TI - The daily news. PMID- 2224823 TI - Coordinating a preceptorship program. PMID- 2224824 TI - The road to Aus. PMID- 2224825 TI - [Injections]. AB - This article deals with the injection techniques used for administering medication in the vastus lateralis and the ventral gluteal muscles. Both sites are easy to locate and safe for injection. The vastus lateralis site, in particular, is commonly used for babies, children and adults. PMID- 2224826 TI - [Sexuality in the Cree culture]. AB - This study focuses on the traditional elements of Cree sexuality, and the impact that white society has had on Cree culture. A questionnaire, administered to persons knowledgeable of the Cree, reveals the reasons for marriage, the nature of sexual relations and the importance of fertility. The author points out specific challenges in the areas of sexuality and family planning that face professionals working with the Cree. PMID- 2224827 TI - Taking issue. PMID- 2224829 TI - Neuron imaging with Neurolucida--a PC-based system for image combining microscopy. AB - Neurolucida is a new software package for performing 3-D neuron mapping and tracing to 0.5 micron precision through the oculars of a microscope. It incorporates computer controlled stage movement in three dimensions. Sections are limited in size only by the stage dimensions. An on-line, direct view image editor is provided as are dynamic image rotations in color and morphometric analyses. Neurolucida is written in 'C' and runs on PC ATs, XTs, and PS/2s using DOS and VGA, EGA, or NTSC graphics. Neurolucida has a video mode compatible with frame grabbers, thereby permitting its application to video microscopy. PMID- 2224828 TI - Image analyzers for bioscience applications. AB - Image analysis systems are becoming more sophosticated, less costly, and very common in research laboratories. Therefore, the bioscience researcher is faced with a bewildering array of choices in establishing an image analysis facility. Critical components and characteristics of commercial image analyzers are discussed. State-of-the-art systems feature a graphical user interface, a powerful operating system (e.g., Microsoft OS/2), 1000 line image acquisition, processing and display, true color imaging, and very flexible scanner interfaces. Such systems are best suited to technically difficult applications, such as ratio fluorescence, or to automated analysis of anatomical features, particularly in stained material. Less powerful image analyzers offer medium resolution, and typically work with monochrome data acquired from video cameras. Such systems are suitable for many bioscience applications, including quantitative autoradiography and routine morphometry. PMID- 2224830 TI - CARTOS II semi-automated nerve tracing: three-dimensional reconstruction from serial section micrographs. AB - The paper describes the history of tracing activities in the Levinthal lab from 1965 to the present. It also focuses on the evolution of electron micrograph (EM) tracing from early hand tracing reconstruction to the current, nearly fully automated CARTOS II tracing system. The present hardware systems and tracing algorithms are described in detail. Also presented are the partial tracing results of one EM data set in two and three dimensions. PMID- 2224831 TI - The variation in user drawn outlines on digital images: effects on quantitative autoradiography. AB - Variation in user outlines drawn to delineate neural regions is the only source of error added to autoradiographic images after the images have been digitized. By analyzing data compiled from many outlines drawn by several different investigators, it was demonstrated that this variation constitutes a major source of error affecting quantitative autoradiography. Both the gray level variation and average within a region, as well as the specific pixels included in an outline, were affected. However, using the intersection of multiple outlining attempts surrounding any given region and a consistent set of outlining criteria, it was possible to delineate a region which remained consistent from user to user. A technique for automating the consistent outlining process is discussed. PMID- 2224832 TI - Recognition of regions in brain sections. AB - This paper addresses the problem of region identification in sequential brain sections and presents a recognition system that finds and tracks region boundaries in those sections. The characteristics of the areas of interest are unique in one sense because they are not stationary. Some regions are hardly discernible. In others, parts of the boundary are missing or so completely blurred that parts of the background may be considered as an extension of the region itself. Moreover, outliers are likely to exist in many cases. Due to the unique properties of brain regions, the emphasis is on robustification and efficiency. The region segmentation problem was expressed as a multi-hypothesis test seeking boundaries that maximize a performance criterion which is general in terms of blur and noise. Boundary candidates are restricted to an adaptive search area around a reference boundary which is usually the outcome of the algorithm from the previous section. The search for the maximum criterion uses a fast first order dynamic programing (DP) procedure, reducing the processing time. Outlier rejection techniques are integrated with the multi-hypothesis test to compensate for both outliers and noise. The result is the reference for the next section. Experimental results on boundary detection are presented. The algorithm is successful in tracing boundaries when the contrast is smaller than the noise power, and when parts of the outlines are missing. PMID- 2224833 TI - A PC-based 3D imaging system: algorithms, software, and hardware considerations. AB - Three-dimensional (3D) imaging in medicine is known to produce easily and quickly derivable medically relevant information, especially in complex situations. We intend to demonstrate in this paper, that with an appropriate choice of approaches and a proper design of algorithms and software, it is possible to develop a low-cost 3D imaging system that can provide a level of performance sufficient to meet the daily case load in an individual or even group-practice situation. We describe hardware considerations of a generic system and give an example of a specific system we used for our implementation. Given a 3D image as a stack of slices, we generate a packed binary cubic voxel array, by combining segmentation (density thresholding), interpolation, and packing in an efficient way. Since threshold-based segmentation is very often not perfect, object-like structures and noise clutter the binary scene. We utilize an effective mechanism to isolate the object from this clutter by tracking a specified, connected surface of the object. The surface description thus obtained is rendered to create a depiction of the surface on a 2D display screen. Efficient implementation of hidden-part removal and image-space shading and a simple and fast antialiasing technique provide a level of performance which otherwise would not have been possible in a PC environment. We outline our software emphasizing some design aspects and present some clinical examples. PMID- 2224834 TI - A data exchange format for neuroanatomy workstations. AB - The development of the microprocessor has enabled biomedical researchers to use powerful computers as single user workstations. Many such systems are now in use- some developed for use within individual laboratories, and others purchased commercially. These systems typically mix computer graphics and image processing capabilities. No standard exists that allows users of these workstations to exchange anatomical data in graphical or image form. This paper considers issues involved in designing a flexible format for exchanging digital anatomical data between laboratories. PMID- 2224835 TI - Is there a role for lactobacilli in prevention of urogenital and intestinal infections? AB - This review describes the importance of microbial adhesion in the ecology of the urogenital and intestinal tracts and the influence of host and microbial factors in bacterial interference. In a recent revival of interest in bacterial interference, lactobacillus administration has been studied as a means of treating and preventing disease. Although evidence is conflicting, Lactobacillus acidophilus appears to be involved in beneficial antagonistic and cooperative reactions that interfere with establishment of pathogens in the gastrointestinal tract. The mechanisms of action are believed to involve competitive exclusion and production of inhibitory substances, including bacteriocins. These characteristics, as well as demonstrated adherence abilities in vitro, led to selection of certain Lactobacillus strains for clinical studies of cystitis. Weekly intravaginal Lactobacillus therapy reduced the recurrence rate of uncomplicated lower urinary tract infections in women. Use of Lactobacillus strains resistant to Nonoxynol-9, a spermicide that kills members of the protective normal vaginal flora, may have potential for use in women with recurrent cystitis using this contraceptive agent. In veterinary studies, bacterial interference by administration of probiotics has also been beneficial in disease prevention in animals. Carefully selected bacterial mixtures integrate with the gastrointestinal flora of the animals and can confer disease resistance and improve physiological function. Additional human and animal trials are needed to determine the practical, long-term usefulness of bacterial interference as a protective mechanism against infectious diseases. PMID- 2224838 TI - Unusual reaction to chlorambucil: a case report. AB - In this brief report we describe a case of cutaneous reaction during treatment of chronic lymphatic leukemia (CLL) with chlorambucil. The patient developed a confluent maculopapular erythema and large flaccid bullae of trunk, legs, feet and mucous membranes, with fever up to 38 degrees C. Toxic epidermal necrolisis (TEN) was supposed and the diagnosis was confirmed by a skin patch test followed by cutaneous biopsy. TEN by chlorambucil is a rare syndrome that may be considered in presence of cutaneous reaction to this drug. PMID- 2224839 TI - Persistence of cytogenetic damage induced by alkylating antineoplastic drug phopurinum in human lymphocytes in vivo and in vitro. AB - Sister chromatid exchanges (SCEs) and structural chromosome aberrations (CAs) induced by cytostatic drug phopurinum in vivo and in vitro were studied in human lymphocytes. Phopurinum was found to cause a significant increase of CAs in lymphocytes of patients undergoing cytostatic therapy. Increased CA rates, however, declined rapidly after the cessation of treatment. This decline observed in vivo is in agreement with experimental results obtained in vitro, where it is found that the induction of SCEs and CAs occur only during the 1st cell cycle after pulse-treatment as G1 stage with phopurinum. Thus, phopurinum induced short lived DNA damage both experimentally and in vivo. PMID- 2224840 TI - Synergistic cytotoxic effect of human recombinant tumor necrosis factor alpha combined with dihydroambazone. AB - Dihydroambazone (DHA) is a water-soluble derivative of the experimental anticancer drug ambazone. In vitro, a combination of DHA and human recombinant tumor necrosis factor alpha (TNF) exerted a strong synergism of cytotoxicity against both mouse melanoma B16K cells and the TNF-sensitive mouse fibroblast line L-M (S). Furthermore, in a colony-forming assay with B16K cells a combination of TNF and DHA inhibited colony-formation much more severely than either drug alone. An increased antiproliferative efficiency was also confirmed in vivo against established subcutaneous melanoma B16 tumors of C57BL/6 mice. PMID- 2224841 TI - Increased therapeutic efficacy of intra-arterial carboquone chemotherapy on a limb tumor in rats, by using an acidic vehicle adjusted with lactate. AB - We previously reported that the cytotoxicity of carboquone (CQ) was potentiated in vitro and in vivo under acidic conditions. In this study, an acidic vehicle adjusted with lactate at various low pHs was used for CQ intra-arterial (i.a.) injection, in order to enhance the antitumor effects of i.a. CQ chemotherapy. Treatments were evaluated in Wistar/KA rats bearing a limb tumor 5 days after the inoculation of 3 x 10(6) syngeneic RBT-1 tumor cells into the hind limb. In chemotherapy experiments using an intrafemoral injection of CQ at 1.5 mg/kg in phosphate-buffered saline (PBS, pH 7.4) or in an acidic vehicle at pH 5.0 or 6.0, the antitumor effects seen in rats given CQ in acidic vehicles, evaluated by tumor weight 14 days after treatment, were significantly greater than that seen in rats given CQ in PBS. There were no significant differences either in changes of body weight or in the number of leukocytes after treatment between the groups given CQ in PBS and in an acidic vehicle at pH 6.0. Although in the group given CQ at 2.0 mg/kg in PBS, the antitumor effect was the same as that observed in rats given CQ at 1.5 mg/kg in an acidic vehicle at pH 6.0, the side effects observed in the former group were much severer than in the latter group. These data suggest that the antitumor effect of i.a. CQ chemotherapy can be potentiated by using an acidic vehicle. PMID- 2224842 TI - O6-alkyltransferase activity in normal human gastric mucosa. AB - The spectrum of activity of the DNA repair enzyme O6-alkyltransferase has been studied in a large series of normal stomachs in order to establish the baseline range of values for this enzyme. Sixty-eight patients with histologically normal stomachs were biopsied during the course of upper gastrointestinal endoscopy and the biopsies assayed for O6-alkyl-transferase activity. A wide spectrum of activity was found with values ranging from 38 fmol O6-guanine extracted/mg protein to over 400 fmol/mg. This suggests that there may be wide inter individual differences in susceptibility to alkylating actions in the human gastric mucosa. PMID- 2224843 TI - Induction of N-nitrosodimethylamine metabolism in rat liver and lung by ethanol. AB - The metabolic activation of N-nitrosodimethylamine (NDMA) to an active metabolite is important in the manifestation of its carcinogenic effect. The lung and liver were compared for their responses to the induction of NDMA demethylation by 10% ethanol in the drinking water and by repeated bolus injections. Ethanol in the drinking water increased NDMA metabolism several-fold in both the liver and the lung. Repeated ip injections with 0.6 and 3.0 ml ethanol/kg for 7 days also enhanced this activity in a dose-dependent fashion. These results suggest that in the lung, as in the liver, ethanol may influence the metabolic activation of this nitrosamine. PMID- 2224844 TI - Role of cyclic AMP receptor proteins in growth, differentiation, and suppression of malignancy: new approaches to therapy. AB - Two isoforms of the regulatory subunits of cyclic AMP (cAMP)-dependent protein kinase that bind cAMP are inversely expressed during ontogeny and cell differentiation. These cAMP-binding receptor proteins in harmony may regulate the growth of normal cells and their differentiation into nondividing states. Cancer cells can also be made to differentiate and stop growing when the functional balance of these cAMP receptor proteins is restored by treatment with site selective cAMP analogues or by the use of an antisense oligodeoxynucleotide, suggesting new approaches to cancer treatment. PMID- 2224845 TI - Changes in intratumor pH by two heatings. AB - It is a known fact that pH in rodent tumors decline significantly upon heating most likely due to breakdown of the tumor blood circulation. We recently observed that tumor blood vessels become thermotolerant after being heated with a sublethal thermal dose. The purpose of the present study was to reveal whether heating can reduce intratumor pH when the tumor vessels are thermotolerant. When the SCK tumors of A/J mice were heated at 42.5 degrees C for 1 h, the tumor vessels became most thermotolerant at 18 h postheating, as measured with the 86Rb uptake method. The intratumor pH in the control SCK tumors was 7.05 +/- 0.14 (SD), and it significantly decreased to 6.70 +/- 0.08 (P less than 0.001) after heating at 44.5 degrees C for 1 h. However, when the tumor vessels were thermotolerant, i.e., 18 h after heating at 42.5 degrees C for 1 h, reheating at 44.5 degrees C for 1 h could not reduce the intratumor pH. We concluded that such a failure to increase tumor acidity by a second heating at temperatures as high as 44.5 degrees C was due to vascular thermotolerance developed by the first heating. PMID- 2224846 TI - Patterns of mate drinking in a Brazilian city. AB - Mate drinking, a hot infusion of Ilex paraguayensis commonly drunk in parts of South America, has been associated with increased risks of upper digestive cancers. In a population-based survey, we have studied the patterns of mate drinking in a sample of 1400 adults living in a southern Brazilian city. Approximately one third of the population drank mate less than once a month or not at all; another third drank mate at least once a month, but less than once a day; while the remaining third drank mate daily. Daily drinking was most common among individuals aged under 60, those who migrated from rural areas, and among cigarette smokers. Drinkers ingested on average about 1800 ml/day at a mean temperature of 69.5 degrees C. Individuals who had never attended school tended to ingest larger quantities. The temperature of the drink was higher for males and for drinkers of alcoholic beverages. This information may contribute to the design of preventive interventions, since a large proportion of upper digestive cancer cases in those regions might be due to mate drinking. PMID- 2224837 TI - The dengue viruses. AB - Dengue, a major public health problem throughout subtropical and tropical regions, is an acute infectious disease characterized by biphasic fever, headache, pain in various parts of the body, prostration, rash, lymphadenopathy, and leukopenia. In more severe or complicated dengue, patients present with a severe febrile illness characterized by abnormalities of hemostasis and increased vascular permeability, which in some instances results in a hypovolemic shock. Four distinct serotypes of the dengue virus (dengue-1, dengue-2, dengue-3, and dengue-4) exist, with numerous virus strains found worldwide. Molecular cloning methods have led to a greater understanding of the structure of the RNA genome and definition of virus-specific structural and nonstructural proteins. Progress towards producing safe, effective dengue virus vaccines, a goal for over 45 years, has been made. PMID- 2224848 TI - Effect of tamoxifen on DNA synthesis and proliferation of human malignant glioma lines in vitro. AB - Previous studies in our laboratory have shown that proliferation of human malignant gliomas in vitro depends in part upon the activation of protein kinase C (PKC) and, conversely, can be blocked by inhibitors of PKC. Here, we examined the effect of tamoxifen, a known PKC inhibitor, on DNA synthesis and proliferation of an established human glioma line (U138) and two low passage cultures of explanted human glioblastomas. Tamoxifen produced a profound, dose dependent inhibition of both [3H] thymidine incorporation and cell proliferation, with a 50% effective dose of 20 ng/ml under serum-free conditions and 50 to 200 ng/ml in the presence of 10% serum. These tumors were estrogen receptor negative and showed no mitogenic response to estradiol. Furthermore, concentrations of estradiol as high as 10 micrograms/ml had no effect on the tamoxifen-induced inhibition. This suggests that the mechanism of growth inhibition by tamoxifen in these gliomas did not involve an estrogen receptor-mediated process but may instead result from its inhibition of PKC. In view of the profound effect of tamoxifen on cultured gliomas at concentrations that can safely be achieved therapeutically, further in vitro and in vivo studies of this agent are warranted. PMID- 2224847 TI - Occupations of parents of children with retinoblastoma: a report from the Children's Cancer Study Group. AB - A matched case-control study was conducted by the Children's Cancer Study Group to investigate the role of parental occupation in the etiology of sporadic heritable and nonheritable retinoblastoma. Eligible cases were those patients with retinoblastoma diagnosed in 1982-1985 at any of the Children's Cancer Study Group member hospitals. Telephone interviews of 201 parents of cases and their pair-matched controls selected by random digit dialing were completed. Of the 201 cases, 19 were familial, 67 were sporadic heritable, and 115 were nonheritable. The 19 familial cases were excluded from the analysis. Paternal employment in the military [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.1-8.8, P = 0.04] and in the metal industry (OR infinity, 95% CI 1.4-infinity, P = 0.02) was associated with sporadic heritable retinoblastoma (N = 67). For nonheritable retinoblastoma (N = 115), a significant association was observed for a job cluster consisting mostly of welders and machinists (OR 4.0, 95% CI 1.1-22.1, P = 0.04). Occupations of maternal grandparents were also studied and an association was observed with farming and nonheritable retinoblastoma (OR 10.0, 95% CI 1.4 433, P = 0.02). Many comparisons were made and the number of significant findings did not exceed that expected by chance. Thus, the results need to be interpreted very cautiously. However, the findings related to metal exposure corroborate observations on other childhood cancers. PMID- 2224849 TI - Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture. AB - Dietary lipids may influence breast cancer progression and prognosis. The MDA-MB 231 human breast cancer cell line was used to examine the direct effects of the various classes of free fatty acids (FAs) on growth in serum-free medium and the involvement of eicosanoid biosynthesis. Linoleic acid, an omega 6 FA, stimulated MDA-MB-231 cell growth with an optimal effect at a concentration of 0.75 microgram/ml, whereas oleic acid, an omega 9 FA, produced growth stimulation at 0.25 microgram/ml but was inhibitory at higher concentrations. Docosahexaenoic acid exhibited a dose-related inhibition of cell growth at concentrations ranging from 0.5 to 2.5 micrograms/ml; eicosapentaenoic acid, also an omega 3 FA, was less effective. Similar inhibitory effects occurred with saturated FAs. Indomethacin, which at high concentrations is an inhibitor of both the cyclooxygenase- and lipoxygenase-catalyzed pathways of eicosanoid synthesis, suppressed cell growth stimulation by an otherwise optimal dose of linoleic acid when present at 40 micrograms/ml. Experiments with piroxicam, nordihydroguaiaretic acid, and esculetin, other inhibitors of eicosanoid biosynthesis with varying selectivity for enzymes of the prostaglandin and leukotriene pathways, indicated that MDA-MB-231 cell growth was dependent on leukotriene rather than prostaglandin production. PMID- 2224851 TI - Correlation between seric antitumor activity and concomitant resistance in mice bearing nonimmunogenic tumors. AB - Serum from mice bearing five weakly immunogenic or nonimmunogenic tumors inducing concomitant resistance exhibited a growth-inhibitory activity on in vitro proliferation of the tumor cells. This activity was proportional to the intensity of concomitant resistance and correlated with the capacity to restrain metastatic development. It was not attributable to cytotoxic antibodies, was relatively nonspecific, and operated through a cytostatic and reversible mechanism. All attempts to transfer antitumor resistance in vivo by serum inoculation have failed, but this could be attained by parabiosis. Physical and chemical serum treatments suggest that heat-, acid-, and alkali-resistant peptide(s) with molecular weights ranging from 1000 to 3000 could account for this inhibitory effect. PMID- 2224850 TI - In vitro migration of lymphocytes through collagen matrix: arrested locomotion in tumor-infiltrating lymphocytes. AB - Antitumor immunity requires (a) extravasation of lymphocytes from the blood stream to interstitium, (b) locomotion through extracellular matrix to the site of the tumor, (c) effector cell recognition of the tumor target with cell/cell contact and binding of adhesion receptors, (d) T-cell receptor binding to histocompatibility and tumor antigens, and (e) tumor cell lysis. We hypothesize that the tumor microenvironment inhibits lymphocyte locomotion through extracellular matrix as one mechanism by which tumors may avert host defense. Lymphocyte locomotion was investigated in vitro using a three-dimensional collagen gel model. Fresh tumor-infiltrating lymphocytes (TIL) were obtained by enzymatic digestion of melanomas and renal cell carcinoma, and mononuclear cells were isolated by discontinuous Ficoll-Hypaque gradient. The lymphocytes were analyzed for motility from a point of origin between basal and overlay layers of collagen gel. Results showed that TIL migration was almost completely inhibited, compared with migration of normal and cancer patient peripheral blood leukocytes and lymphocytes from lymph nodes. Short-term (24-h) exposure of lymphocytes to cytokines during the assay in the collagen gel matrix had no effect on locomotor ability. Long-term (19, 30, or 35 days) culture of TIL in 200 units/ml of interleukin 2 reinstated locomotor ability. Short-term exposure of any of the lymphocyte populations to interleukin 1-alpha, interleukin 1-beta, interleukin 2, interleukin 3, interleukin 4, alpha-interferon, or gamma-interferon had no effect on migration. Thus, TIL display a uniquely arrested ability to locomote through collagen gel. Inhibition of the locomotion of infiltrating effector cells is possibly a mechanism by which the tumor evades the host immune system. PMID- 2224836 TI - Some infectious causes of diarrhea in young farm animals. AB - Escherichia coli, rotaviruses, and Cryptosporidium parvum are discussed in this review as they relate to enteric disease in calves, lambs, and pigs. These microorganisms are frequently incriminated as causative agents in diarrheas among neonatal food animals, and in some cases different strains or serotypes of the same organism cause diarrhea in humans. E. coli causes diarrhea by mechanisms that include production of heat-labile or heat-stable enterotoxins and synthesis of potent cytotoxins, and some strains cause diarrhea by yet undetermined mechanisms. Rotaviruses and C. parvum induce various degrees of villous atrophy. Rotaviruses infect and replicate within the cytoplasm of enterocytes, whereas C. parvum resides in an intracellular, extracytoplasmic location. E. coli, rotavirus, and C. parvum infections are of concern to producers, veterinarians, and public health officials. These agents are a major cause of economic loss to the producer because of costs associated with therapy, reduced performance, and high morbidity and mortality rates. Moreover, diarrheic animals may harbor, incubate, and act as a source to healthy animals and humans of some of these agents. PMID- 2224852 TI - Ether-linked phosphoglyceride content of human leukemia cells. AB - The glycerolipids of most cells are characterized by a specific proportion of ether linkages at the sn-1 position of the glycerol backbone. A number of tumors are known to have altered concentrations of ether-linked lipids compared to normal tissues. However, no through examination of the ether-lipid content of human leukemia cells has been reported despite the importance of these lipids in normal leukocyte function. In the present study samples were obtained from adults with acute myelogenous leukemia (AML), chronic granulocytic leukemia in blast crisis, and acute lymphocytic leukemia and from healthy human donors. The cellular lipids were extracted, the individual phospholipid classes were isolated, lipid phosphorus content was determined, and the lipids were converted to diglyceride benzoate derivatives for separation and quantitation of the subclasses by high performance liquid chromatography. The data indicate that all the leukemic cells analyzed have an altered phospholipid composition compared to their respective normal leukocytes. Furthermore, among the AML patients both the percentage of the choline-containing phosphoglyceride fraction (PC) which is alkyl linked and the nmoles alkyl-PC/10(6) cells differ significantly by FAB subtype. A positive correlation between the levels of alkyl-PC and the degree of cellular differentiation is observed. Although no differences are observed between chronic granulocytic leukemia in blast crisis and AML lipids, the leukemic cells contain dramatically lower levels of alkyl-linked PC than do normal polymorphonuclear leukocytes. In contrast, no differences are observed between the alkyl-PC content of normal and leukemic lymphocytes. In light of the relations among ether-lipids, protein kinase C, and cell differentiation, these data suggest the ether-linked lipids are important in myeloid cell function and differentiation. PMID- 2224854 TI - Phase I trial of dipyridamole with 5-fluorouracil and folinic acid. AB - We have performed two Phase I trials of the combination of dipyridamole, 5 fluorouracil (5-FU), and folinic acid in patients with advanced refractory malignancy, based upon in vitro evidence that dipyridamole can modulate the cytotoxicity of 5-FU. In the first trial, patients were treated every 4 wk with dipyridamole (50 mg/m2) p.o. every 6 h on Days 0 to 6, beginning 24 h prior to the i.v. administration of folinic acid (200 mg/m2) and escalating doses of i.v. 5-FU on Days 1 to 5. The maximum tolerated daily dose of 5-FU that could be given with this combination was 375 mg/m2. Because dipyridamole is extensively bound to plasma proteins, it was hypothesized that the concentrations of free dipyridamole achieved with a dose of 50 mg/m2 were inadequate to modulate the cytotoxicity of 5-FU and folinic acid. Therefore, a second Phase I trial of escalating dose of p.o. dipyridamole was performed. Folinic acid (200 mg/m2) and 5-FU (375 mg/m2) were given i.v. on Days 1 to 5 every 4 wk, beginning 24 h after the start of therapy with dipyridamole; dipyridamole was administered p.o. on Days 0 to 6 at doses of 75, 100, 125, 150, 175, or 200 mg/m2/dose to successive cohorts of patients. Dose-limiting neutropenia, mucositis, and nausea were produced at a dose of 200 mg/m2/dose; the recommended dose of dipyridamole for use in Phase II studies is 175 mg/m2 p.o. every 6 h, or 700 mg/m2/day. At this dose, a mean peak plasma concentration of total dipyridamole of 16.32 mumol and a mean peak plasma concentration of free dipyridamole of 38.30 nmol were observed. Trough concentrations of free dipyridamole averaged 60% of the peak concentrations. Objective antitumor responses were seen in a number of tumor types; five of 13 patients with breast cancer treated with high-dose p.o. dipyridamole, 5-FU, and folinic acid responded. High-dose p.o. dipyridamole can produce plasma concentrations of free dipyridamole within the range shown to modulate the cytotoxicity of 5-FU and other agents. Phase II trials of this combination are justified. PMID- 2224853 TI - Role of insulin-like growth factor-related peptides in the estradiol-, prolactin , and progesterone-stimulated growth of N-nitrosomethylurea-induced rat mammary tumors in soft agar. AB - The present experiments were designed to test the role of insulin-like growth factor-related peptides (IGF-RPs) in hormonally stimulated N-nitrosomethylurea (NMU)-induced mammary tumor colony formation in soft agar. To evaluate production of IGF-RP by NMU cells, we tested the abilities of a monoclonal antibody directed against insulin-like growth factor I (alpha sm 1.20B) and of a polyclonal antibody raised against the insulin-like growth factor I (Ab 134) to inhibit the colony-stimulating effects of conditioned media (CM) obtained from estradiol (E2) , prolactin (PRL)-, and progesterone (Pg)-treated NMU-induced rat mammary tumors. Both Abs abolished the colony-stimulating action of genuine insulin-like growth factor I while having no effect when added alone or with control CM. The addition of either alpha sm 1.20B or Ab 134 (but not that of an irrelevant Ab) consistently blocked the colony-stimulating action of E2-CM, PRL-CM, and Pg-CM, suggesting that IGF-RPs are produced by NMU mammary tumor cells exposed to these hormones. Next, we directly tested the role of IGF-RPs as mediators of hormonally stimulated growth. We indeed observed that the addition of alpha sm 1.20B markedly inhibited the colony-stimulating actions of E2, PRL, and Pg added to NMU mammary tumor cells in soft agar in the absence of serum. We conclude that, in our experimental system, IGF-RPs not only are produced upon exposure to E2, PRL, and Pg, but also are important mediators of hormonally stimulated growth. PMID- 2224855 TI - Inhibitory effects of estrogen on the growth of a human esophageal carcinoma cell line. AB - In order to accurately determine sex hormone dependency and hormone responsiveness in human esophageal carcinoma, the effects of sex hormones on the growth of esophageal carcinoma cell lines, KSE-1 and KSE-2 cells, were examined in vitro and in vivo. Cell proliferation of cultured KSE-1 cells was inhibited by treatment of estradiol and enhanced by dihydrotestosterone (DHT), whereas KSE-2 cells were unaffected by these sex hormones. The heterotransplanted tumors of KSE 1 cells in nude mice possessed estrogen receptor (ER) and androgen receptor (AR), while the tumors of the KSE-2 cells had neither ER nor AR. When the tumor growth rates and serum hormone levels were monitored during the continuous administration of either estradiol or DHT, no significant differences were observed in either the serum hormone levels or tumor growth rates between male and female mice. The administration of estradiol significantly inhibited the growth of ER-positive and AR-positive KSE-1 tumors in both males and females in conjunction with an increase in the estradiol levels and a decrease in the DHT levels in the serum. However, the growth of ER-negative and AR-negative KSE-2 tumors was not influenced by either estradiol or DHT administration. These results suggest that the in vivo growth of human esophageal carcinoma cells with sex hormone receptor is influenced by circulating hormone levels and can be manipulated by systemic estradiol administration. PMID- 2224856 TI - Phorbol ester-induced macrophage-like differentiation of human promyelocytic leukemia (HL-60) cells occurs independently of transferrin availability. AB - Human promyelocytic leukemia (HL-60) cells can be induced to differentiate into macrophage-like cells by the tumor-promoting phorbol ester, 12-O tetradecanoylphorbol-13-acetate (TPA). Addition of this agent to HL-60 cells causes a rapid internalization of surface transferrin receptor, followed by long term receptor down-regulation at the level of gene expression. These effects precede the inhibition of proliferation and the acquisition of differentiation markers, and it has been suggested that transferrin receptor down-regulation may play a mediating role in these later events. Here we show that HL-60 cells will grow indefinitely in serum-free medium supplemented with either 5 micrograms ml-1 transferrin or 300 microM ferric citrate and that TPA inhibits cell proliferation (assayed by cell density and rate of thymidine incorporation) and induces macrophage-like differentiation (assayed by induction of cell adhesion and increased nonspecific esterase activity) with identical dose curves in both media. Furthermore, a neutralizing anti-transferrin antibody completely inhibits transferrin-dependent cell proliferation but has no effect on differentiation in the presence or absence of transferrin. We conclude that TPA-induced down regulation of transferrin binding and internalization does not mediate the subsequent growth arrest and differentiation of HL-60 cells. PMID- 2224857 TI - Radiolocalization of human pancreatic tumors in athymic mice by monoclonal antibody DU-PAN 1. AB - Monoclonal antibodies that selectively bind to pancreatic tumors may be useful in the therapy and diagnosis of pancreatic carcinoma. In this study we have examined the tumor localization of radioiodinated DU-PAN 1, a mouse monoclonal antibody that is selective for a human pancreatic cancer-associated antigen. After radiolabeling, both DU-PAN 1 intact monoclonal antibody and F(ab')2 fragments retained immunoreactivity and showed high affinity for the pancreatic tumor cell line CA13 in vitro. Paired-label biodistribution studies in nude mice bearing CA13 s.c. xenografts were performed. Mice received both 131I-labeled DU-PAN 1 immunoglobulin G2a or F(ab')2 fragment and 125I-labeled mouse myeloma immunoglobulin G2a or F(ab')2 fragment. Tumor uptake for 5-micrograms doses of DU PAN 1 immunoglobulin ranged from 4.8 to 11.83% injected dose/g. Tumor uptake values for mice given 5-micrograms doses of DU-PAN 1 F(ab')2 ranged from 3.9 to 6.9% injected dose/g. Tumor uptakes of the respective myeloma controls were lower in all cases when compared with the DU-PAN 1 preparations. Tumor localization indices for 5-micrograms doses of DU-PAN 1 immunoglobulin were 3.0 and 24 h and 2.9 at 48 h. For 5-micrograms doses of DU-PAN 1 F(ab')2, tumor localization indices were 29.9 at 24 h and 90.0 at 48 h. In most cases, tumor:normal tissue ratios were greater than 3 at all time points, indicative of tumor selectivity for both DU-PAN 1 preparations, but the ratios were considerably higher using the DU-PAN 1 F(ab')2. The F(ab')2 fragment thus displays better tumor localization characteristics when compared with the intact immunoglobulin. Protein doses of DU PAN 1 F(ab')2 of between 5 and 10 micrograms gave the best localization, although protein doses of up to 100 micrograms could be administered before apparent tumor saturation was seen. PMID- 2224858 TI - Pharmacokinetics in patients of an anti-carcinoembryonic antigen antibody radiolabeled with indium-111 using a novel diethylenetriamine pentaacetic acid chelator. AB - The pharmacokinetics of the C110 anti-carcinoembryonic antigen antibody radiolabeled with 111In via a novel benzylisothiocyanate derivative of diethylenetriamine pentaacetic acid have been determined in 12 patients. The chelator was attached to the protein via a thiourea bond and in such a way that all 5 carboxymethyl arms were presumably able to participate in chelation. Patients with known or suspected colorectal carcinoma received between 5 and 20 mg of the IgG antibody labeled with 5 mCi of 111In. Individual organ radioactivity levels were quantitated, and serum and urine samples were analyzed, principally by size exclusion high-performance liquid chromatography (HPLC). Total urinary excretion averaged 0.18% of the injected dose/h with large patient to patient variation. At early times postadministration (less than 8 h) the predominant radiolabeled species in urine was free diethylenetriamine pentaacetic acid most probably administered as a small radiocontaminant in the injectate. Thereafter, radioactivity in urine was primarily present as a low molecular weight catabolic product. Analysis of serum by size exclusion HPLC occasionally showed 3 radioactivity peaks, 2 of which are due to circulating immune complexes and labeled antibody. The third peak is of low molecular weight and is due to one or more products of antibody catabolism. Transchelation of 111In to circulating transferrin was observed but at modest levels. Quantitation of organ radioactivity showed that 18 +/- 4 (SD)% of the injected dose was in the liver at 1 day postadministration and 1.4 +/- 1.1 and 1.2 +/- 0.9% was in the spleen and in both kidneys, respectively, at this time. The mean half-life for clearance of total injected radioactivity was fitted to a single exponential and was found to be 34 h (SD, 14 h; N = 13) and that for antibody alone, assessed by size exclusion HPLC analysis of serum samples, was calculated to be 22 h (SD, 8 h; N = 10). Neither of these values nor organ radioactivity levels were affected by antibody-loading dose. PMID- 2224860 TI - Inhibition of in vivo tumor growth by a monoclonal IgM antibody recognizing tumor cell surface carbohydrates. AB - We have shown previously that IgM from Ehrlich tumor (ET)-immunized mice, recognizing ET cell surface carbohydrates, protects control mice to a subsequent tumor challenge. The factors involved in such IgM-mediated protection were unknown, since it was independent of complement activation. Here, we have extended these in vivo studies by means of monoclonal IgM antibodies. Two of them (A10 and E1), strongly recognizing ET cells and with specificity to ET cell surface carbohydrates, were selected. The results show that A10 (but not E1 or unrelated IgM antibodies) is able to protect nonimmunized mice against ET growth. Protection by A10 was also seen by reducing 800-fold the initial dose; however, E1 was unsuccessful whatever the dose used. A10-mediated protection was observed in C3-defective mice (cobra venom factor treated) or in C5-deficient DBA/2, but not in silica-treated animals. Endotoxin removal did not affect the protection afforded by A10 while specific IgM depletion prevented any protective effect. In addition, the relationship between natural antibodies of IgM isotype recognizing ET cell surface carbohydrates and mouse strain resistance to this tumor is established. Similarly, this natural resistance seems to be complement independent but macrophage mediated. Therefore, these results indicate that some IgM molecules recognizing cell surface carbohydrates may participate in in vivo tumor suppression by a macrophage-dependent mechanism. PMID- 2224859 TI - Characterization of a receptor-negative, hormone-nonresponsive clone derived from a T47D human breast cancer cell line kept under estrogen-free conditions. AB - We have established an estrogen receptor- and progesterone receptor-negative, hormone-nonresponsive breast cancer cell line from a receptor-positive, hormone responsive line grown under estrogen-free conditions. T47D breast cancer cells were cultured under estrogenized conditions (in phenol red-containing medium supplemented with whole fetal bovine serum) and cloned to produce line T47D:A18. The parental T47D line was also estrogen deprived (in phenol red-free medium supplemented with dextran-coated charcoal-treated fetal bovine serum) for more than 1 year and subsequently clone T47D:C4 was established. T47D:A18 was estrogen receptor and progesterone receptor positive as determined by both ligand binding assay analysis and enzyme immunoassay analysis. T47D:C4 cells were estrogen receptor and progesterone receptor negative and mRNA for these receptors was not detected. Incubation of hormone-responsive T47D:A18 cells with 17 beta-estradiol caused a 3-fold increase in cell growth over 8 days when compared to control. This stimulation of growth was completely inhibited by the anti-estrogens 4 hydroxytamoxifen (0.1 microM) and ICI 164,384 (1.0 microM). Receptor-negative T47D:C4 cells were refractory to the effects of both 17 beta-estradiol and the antiestrogens. T47D:A18 cells grown under both estrogen-containing and estrogen free conditions expressed low levels of transforming growth factor (TGF)-alpha and epidermal growth factor receptor mRNA. In the presence of estrogen, high levels of TGF-beta 1 mRNA were detected in T47D:A18 cells. These levels decreased when T47D:A18 cells were grown in estrogen-free media. Conversely, TGF-beta 2 mRNA was not detected in T47D:A18 cells cultured under estrogenic conditions; however, message was detected after the cells were cultured under estrogen-free conditions. T47D:C4 cells expressed low levels of TGF-alpha, epidermal growth factor receptor, TGF-beta 1, and TGF-beta 2 mRNA. These studies characterize a novel hormone-nonresponsive cell line which has been established from a hormone responsive cell line grown under estrogen-free and drug-free conditions. Further analysis of these lines should provide valuable information concerning the development of antiestrogen-resistant breast cancer. PMID- 2224861 TI - Characterization and distribution in human tissues of a glycoproteic antigen defined by monoclonal antibody 1BE12 raised against the human breast cancer cell line T47D. AB - Spleen cells from inbred Biozzi mice, immunized against the human breast cancer cell line T47D, were fused with murine myeloma SP2O cells to generate monoclonal antibodies. One of these, 1BE12, of IgM isotype, reacted with five of six human breast tumor cell lines, while no binding was detectable with normal lymphocytes, RBC, or fibroblasts. The antigen recognized by monoclonal antibody 1BE12 was localized on the surface of T47D and MCF7 cells and was detected in cell-free supernatants of cultures. The antigen was found also on the surface of milk secretory cells. Immunohistochemical staining of frozen and paraffin-embedded sections of human tissues showed apical polarized reactivity in normal breast glands, while in all breast cancers staining was either cytoplasmic or membranous and heterogeneously distributed. Immunostaining was also observed in some other normal epithelia, including salivary gland, gastroduodenal mucosa, exocrine pancreas, and cervix. The antigen was not detectable in secretory endometrium, whereas proliferative endometrium was strongly stained. Colon carcinoma, and cancers of the bladder and endometrium were strongly reactive. No staining was detected in melanoma, lymphoma, mesothelioma, non-small cell lung carcinoma, and thyroid, renal, and ovarian carcinomas. Lectin absorption of MCF7 membrane extracts reduced 1BE12 binding. A large reduction in 1BE12 reactivity was observed after digestion of T47D and MCF7 membrane extracts with proteases. Treatment with sodium periodate resulted in complete loss of antigenicity, while neuraminidase treatment did not affect 1BE12 binding. These findings suggest that the 1BE12 epitope is expressed on the carbohydrate moiety of a glycoprotein and does not contain sialic acid. Immunoblotting of the perchloric acid-soluble fraction of MCF7 membrane extracts after electrophoresis in 1% agarose detected the antigen as a high molecular weight species (Mr greater than 900,000). The antigen was purified by perchloric acid extraction of MCF7 membrane preparations followed by affinity chromatography on 1BE12 antibody coupled to Sepharose-4B and gel exclusion fast protein liquid chromatography. No reactivity of the purified material was found with monoclonal antibodies directed against human milk fat globule membrane-associated mucins HMFG1 and DF3. PMID- 2224862 TI - Interleukin 2 and lymphokine-activated killer cell therapy: analysis of a bolus interleukin 2 and a continuous infusion interleukin 2 regimen. AB - Several groups have described the efficacy of interleukin 2 (IL-2) plus lymphokine-activated killer (LAK) cells in the treatment of cancer patients with significant response rates noted in patients with renal cell cancer and malignant melanoma; however, the optimum regimen remains undefined. The Biological Response Modifiers Program of the National Cancer Institute conducted two consecutive Phase I/II studies evaluating the toxicity and clinical efficacy of different methods of IL-2 and LAK cell therapy. In the first trial, we modified the standard Rosenberg regimen by decreasing the duration of priming in an attempt to reduce the toxicity related to this phase of the therapy and thereby administer more IL-2 doses with the LAK cells. In the second trial, we used a continuous i.v. infusion IL-2 regimen and altered both the leukapheresis procedure and the LAK cell culture techniques based on our in vitro and preclinical studies suggesting that 2-day LAK cells were superior. Thirty cancer patients received i.v. bolus IL-2 at 100,000 units/kg every 8 h for 3 days during priming and for 5 days during LAK cell administration. A second group of 22 cancer patients received IL-2 by continuous i.v. infusion at 3 x 10(6) units/m2 for 5 days during priming and an additional 5 days of IL-2 with the LAK cell phase of the treatment. The timing of the start of the leukapheresis procedures, their duration and number, and the LAK cell culture techniques differed in the two trials. Overall, 52 patients with various cancers were treated. The toxicities associated with each regimen were similar to those seen in other IL-2 plus LAK cell trials. Four patients (one each with melanoma and diffuse large cell lymphoma and two with renal cell cancer) exhibited partial responses lasting 2, 4, 10, and 15+ mo. Serial tumor biopsies from treated patients demonstrated that therapy can produce a marked mononuclear cell infiltrate and an increase in HLA DR expression on tumor cells. There was no difference in the overall response rate between the two regimens, but toxicity was less with continuous i.v. infusion IL-2. The 5-day continuous i.v. infusion regimen resulted in significantly higher rebound lymphocytosis, cell yield from leukapheresis, and number of LAK cells harvested from culture. PMID- 2224863 TI - In vivo invasion assay of low passage cultured cells derived from human lung cancer using deepithelialized rat tracheas xenotransplanted into nude mice. AB - Human lung tumor-derived cell lines with low passage generation were transplanted into nude mice to determine their growth behavior and invasive potential. Six cell lines (HKT-2, HKT-3, HKT-5, HKT-6, HKT-7, HKT-8) were inoculated into deepithelialized rat trachea (5 x 10(5) cells/trachea). After cell inoculation, the tracheas were sealed and transplanted into the subcutis of nude mice. In a parallel experiment, these cell lines (1 x 10(6) cells) were injected s.c. In the subcutis, the tumor take rate of HKT-3, the lowest of all, was only 13% with a long latency period of 18 weeks, and 3 cell lines (HKT-2, HKT-3, HKT-7) did not show any invasive growth to the surrounding tissue. In rat tracheas, all cell lines proliferated within 3 weeks, and 4 of them (HKT-2, HKT-5, HKT-6, HKT-8) showed invasive growth to the tracheal wall within 1-2 weeks. Cells growing in the tracheal wall showed higher [3H]thymidine labeling indexes and greater atypia, such as larger nuclei and prominent nucleoli, than those in the tracheal lumen. The s.c. tumor take rate correlated with the incidence of invasive growth to the tracheal wall. The survival of the patients originally bearing the six tumors also correlated closely with the invasive potential of this system. These results indicate that the system using low passage cell lines can evaluate the invasive potential shortly after the inoculation of a relatively small number of cells and can be used as a clinically reliable biological invasion assay. PMID- 2224864 TI - Down-regulated c-myb expression inhibits DNA synthesis of T-leukemia cells in most patients. AB - We have investigated the functional relevance of c-myb expression for DNA synthesis in patients' T-leukemia cells. [3H]Thymidine incorporation assays of 32 patients' leukemia cells exposed in vitro to c-myb sense or antisense oligodeoxynucleotides served to define two groups of patients: a responder group whose leukemia cells showed 2- to 16-fold lower levels of [3H]thymidine incorporation in c-myb antisense-treated cultures than in c-myb sense-treated cultures (20 patients) and a nonresponder group whose cells showed comparable [3H]thymidine incorporation levels in either c-myb sense- or antisense-treated cultures (12 patients). Down-regulation of c-myb mRNA levels in cells exposed to c-myb antisense oligodeoxynucleotides was comparable in both groups of patients, indicating that differential sensitivity to c-myb antisense oligodeoxynucleotides was not due to differential uptake of these oligodeoxynucleotides. DNA polymerase alpha mRNA levels were down-regulated in cells from the responders but were unaffected in the nonresponder group. These results suggest that c-myb is required for DNA synthesis in cells of many but not all T-leukemia patients and that leukemia cells in which DNA synthesis is not inhibited despite down regulation of c-myb expression may have undergone some genetic change(s) that obviate(s) the requirement for myb protein. PMID- 2224865 TI - Contrast-enhanced magnetic resonance imaging of tumor-bearing mice treated with human recombinant tumor necrosis factor alpha. AB - Pharmacological effects of recombinant human tumor necrosis factor alpha (TNF) were studied in a mouse fibrosarcoma model using magnetic resonance imaging enhanced with a macromolecular contrast agent, albumin(gadolinium diethylenetriamine pentaacetic acid)35. TNF was administered i.v. in a dose of 150 micrograms/kg, 60 to 80 min prior to imaging. Contrast-enhanced and nonenhanced magnetic resonance images of TNF-treated (n = 10) and untreated (n = 8) Meth A fibrosarcomas were obtained at 2.0 Tesla using T1-weighted spin-echo pulse sequences. Serial images spanning an interval of 60 to 120 min after TNF administration showed that the TNF-treated tumors enhanced significantly more overall than did untreated tumors (43% versus 31%). The most marked differential tumor enhancement was observed in the tumor rim (59% versus 40%). Nontumorous tissue, including muscle and brain, revealed no significant enhancement differences between TNF-treated animals and controls. The observed tumor enhancement corresponded strongly with Evans blue staining; the TNF-treated tumors stained deep blue, while untreated tumors and normal tissues observed did not stain. The different enhancement and Evans blue staining patterns between TNF treated tumors and untreated tumors are attributed to TNF-induced changes in tumor capillary integrity. The data indicate that TNF effects on tumors include an increased capillary permeability for macromolecules at early times after administration. The ability to detect changes in capillary permeability in vivo using contrast-enhanced magnetic resonance imaging may prove to be clinically useful to monitor tumor response to TNF. PMID- 2224867 TI - Cancer Research. Index to Volume 50. PMID- 2224866 TI - Pharmacokinetic analysis of immunotoxin uptake in solid tumors: role of plasma kinetics, capillary permeability, and binding. AB - The delivery of cell-specific protein toxins to the interstitium of solid tumors was examined in athymic mice bearing s.c. human rhabdomyosarcoma (TE671) tumors. The toxins are diphtheria toxin (DT), Mr = 60,000, and an immunotoxin, Mr = 210,000. The immunotoxin is a chemical conjugate of a mutant DT defective in binding and a monoclonal antibody specific for the human transferrin receptor. The plasma, tumor, and muscle concentrations of DT, immunotoxin, and closely related nonbinding controls were measured 2, 6, and 24 h after i.v. injection into tumor-bearing mice. Both DT and immunotoxin are specific for the human xenograft in the mouse because DT is very toxic to human cells but not to murine cells and immunotoxin is directed against a human cell receptor. A compartmental pharmacokinetic model was developed for the analysis of the in vivo data to provide plasma-to-tissue transport constants (capillary permeability-area products), binding parameters (products of the association constant and the initial binding site concentration), and the interstitial fluid flow rate. The model also provides a simple mathematical framework for understanding the effect of these variables on the localization of macromolecules in tumors. The plasma-to tissue transport constant of immunotoxin in TE671 tumor was 0.13 microliters/min/g, compared to 0.29 microliters/min/g for DT. However, despite the lower capillary permeability of the larger molecular weight toxin, the cumulative tumor exposure to immunotoxin was 80% higher than that to DT after 24 h. A longer plasma half-life and higher apparent in vivo binding parameter of immunotoxin compared to DT contributed to the higher tumor exposure. Plasma-to tissue transport constants for tumor were 60 to 100% higher than those for muscle. This finding is consistent with observations by others that tumor vasculature is more permeable than are normal muscle capillaries. Also, the interstitial fluid flow of the tumor, 0.80 microliters/min/g, was higher than that of muscle, 0.58 microliters/min/g. The product of the binding affinity and binding site concentration for immunotoxin in vivo was 530 times lower than that predicted based on in vitro measurements. Lower expression of antigen binding sites, inaccessibility of binding sites in vivo, and degradation of the toxin are several possible factors that may account for the in vitro-in vivo differences in binding. This study illustrates the interrelationship of plasma kinetics, capillary permeability, and binding and their effects on toxin concentrations that are achieved in the tissue interstitium. PMID- 2224869 TI - The pattern of metastases in human breast cancer: methodological aspects and influence of prognostic factors. PMID- 2224868 TI - Long-term adjuvant tamoxifen therapy for breast cancer: the prelude to prevention. PMID- 2224870 TI - Chemotherapy for brain metastases: recent developments and clinical considerations. PMID- 2224871 TI - Radiation therapy for squamous cell carcinomas of the oral cavity and oropharynx: a review of recent techniques. PMID- 2224872 TI - Trying to bridge a gap. PMID- 2224873 TI - Intracranial hemorrhage in hypothermic low-birth-weight neonates. AB - We studied periventricular/intraventricular type intracranial hemorrhage (ICH) by cranial ultrasonography in 82 low-birth-weight (LBW) newborn infants with admission hypothermia against the gestational-age-matched 82 normothermic neonates. The incidence of ICH was higher in the hypothermic infants during the 1st week of life (34/82 vs 20/82, P less than 0.02). Although the distribution of individual grades of ICH was not significantly different between the groups, the first ultrasound scan showed higher incidence of major ICH (grades 3 and 4) in the hypothermic infants. Most of the minor ICH (grades 1 and 2) after the first ultrasound appeared in infants who were small for their gestational age. Our data do not support the contention that admission hypothermia can precipitate the development of IVH in LBW infants. However, the detection of admission hypothermia in a LBW neonate should make one suspect the possibility of ICH and regard it as a manifestation of the severity of ICH rather than the cause. Most likely, this close relationship between hypothermia and neonatal ICH originates from perinatal asphyxia and the cumulative adverse effects of asphyxia-related events. PMID- 2224874 TI - Cerebral blood-flow velocity patterns in post-hemorrhagic ventricular dilation. AB - To evaluate the effect of ventricular dilation (VD) on cerebral hemodynamics, serial cerebral bloodflow velocity patterns from the anterior and middle cerebral, and circle of Willis arteries were examined by range-gated, pulsed Doppler sonography in premature infants developing post-hemorrhagic VD. Nine infants (25 to 30 weeks gestation) without a patent ductus arteriosus were studied until resolution of VD. Forty-nine cranial sonograms from all nine infants were reviewed independently and grouped cross-sectionally into mild, moderate and severe VD prior to shunt. The corresponding pulsatility index (PI) showed a consistent trend of increase with VD in all three studied vessels. In six infants, absent or reversed diastolic flow was observed at the height of VD. Four of these infants required V-P shunt. Immediate fall in PI occurred in all three vessels. Serial measurement of PI during VD reflects global changes in cerebrovascular resistance. Results confirmed PI could be a useful index in monitoring cerebral hemodynamic changes. PMID- 2224875 TI - The risk of convulsions: a longitudinal study of normal babies and infants with neonatal damage in the first 6 years of life. AB - After carefully reviewing the epidemiological literature on this subject, we assessed the risk of febrile, isolated or epileptic convulsions in normal babies and infants with neonatal damage. We considered 417 term or preterm infants with birth injury and compared them with 400 healthy full-term newborns, all born between 1978 and 1980, studying each one individually until at least the age of 6 using the chi 2 test, the risk factors in relation to the convulsive outcome in all the groups were processed. We also calculated the relative risk of outcome of both febrile convulsions and epilepsy. Our results show that as far as the onset of seizure disorders in the term infant is concerned, the predisposing factors are asphyxia, neurological syndrome, and previous barbiturate intake. In contrast with this, for premature infants the risk factors are severe apnea and severe prematurity. PMID- 2224876 TI - Tethered cord syndrome versus low-placed conus medullaris in an over-distended spinal cord following initial repair for myelodysplasia. AB - We present findings obtained from a total of 100 patients who had previously undergone surgery for spina bifida and whose progress had been monitored by magnetic resonance imaging (MRI) in our meningomyelocele clinic. Fourteen of these patients (14.0%) developed delayed symptom(s) of progressive spinal neurologic dysfunction. In those with myeloschisis, increase of motor deficit was the most common clinical manifestation during infancy and early childhood (mean age: 6.8 years), whereas pain on back flexion was seen in patients who were over 15 years of age (mean age: 17.3 years). MRI carried out in myeloschisis patients invariably demonstrated that the conus medullaris was in an abnormally low position, suggesting over-distension of the spinal cord. This was irrespective of whether symptom(s) developed or not and did not correlate with the initial surgical procedure (reconstructive or otherwise) used. Patients with symptom(s) were revealed by MRI to have an extremely low conus set at the spinal level of S 1 or below; neurological examinations showed that the motor deficit occurred at high levels in the spine. Results from lipomeningocele patients were more erratic in terms of conus position and delayed development of neurological defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224878 TI - A case of "accessory falx cerebri". AB - We report on a 12-year-old boy who underwent a right frontotemporoparietal craniotomy for complete extirpation of three cavernous hemangiomas of the temporal lobe. On this occasion, an accessory dural septum was observed that spanned, in the direction of the corona, the temporo-occipital base upward to the lower parietal area. It produced a deep notch in the cortex, was supplied by a small leptomeningeal artery, and probably contained small venous sinus. Embryological considerations and clinical relevance are discussed. PMID- 2224879 TI - XVIII annual meeting of the International Society for Pediatric Neurosurgery. Paris, 17-20 September 1990. Abstracts. PMID- 2224877 TI - Clinical experience with a pressure-adjustable valve SOPHY in the management of hydrocephalus. AB - Seventy-four patients with hydrocephalus due to a variety of causes were treated with a cerebrospinal fluid (CSF) shunt, incorporating a recently developed pressure-adjustable valve SOPHY (PAVS). The PAVS may be changed percutaneously with the help of an externally applied magnet in order to select a high-, medium- or low-valve opening pressure, whenever the need for a change in pressure characteristics seems necessary to the neurosurgeon. The percutaneous pressure adjustment obviated up- or downgrading of a medium pressure position by surgical means in half of our patients during the follow-up time (up to 39 months; mean follow-up 16.7 months). In 66 patients (89%) decreased ventricle volume and improvement of the clinical sign of increased intracranial pressure were established. In 11 patients a valve or a catheter infection occurred; in 6 of these patients the valve had to be removed. Half of this group consisted of patients under 2 years of age. Significant technical complications related to the PAVS did not occur in our series but until a somewhat smaller PAVS is available, we cannot recommend its use in neonates or in small infants. In all other patients the PAVS is a very valuable instrument in the surgical management of hydrocephalus because it makes shunt revisions for inadequate valve pressure obsolete in individual patients. PMID- 2224880 TI - X-ray and conformational investigations of a 4:1 mixture of 6-(N-benzyl-N-tert butoxycarbonylamino)-2,3,6,7-tetradeoxy-alpha- DL-ery thro- and -beta-DL-threo hept-2-enopyranos-4-uloses. AB - The crystals of a 4:1 mixture of 6-(N-benzyl-N-tert-butoxycarbonylamino)-2,3,6,7 tetradeoxy-a-DL-er ythro- and -beta-DL-threo-hept-2-enopyranos-4-ulose were monoclinic, space group P2(1)/c, with cell dimensions: a = 9.490(2), b = 21.516(5), c = 10.279(2) A, beta = 115.31(1) degrees, Z = 4. The ulose ring had a half-chair conformation deformed towards the sofa (envelope) form. PMID- 2224881 TI - Semisynthetic epsilon-isorhodomycins: their synthesis using glycals and their structure-activity relationship. AB - Syntheses and structure-activity relationships of 7-O-(3-amino-2,3,6-trideoxy-a-L lyxo- (18), -L-arabino- (20) and -L-ribo- hexopyranosyl)-epsilon-isorhodomycins (25) and their 3'-dimethylamino derivatives 22, 23 and 26 are described. Condensation (trimethylsilyl triflate, molecular sieves 4 A, 10:1 dichloromethane acetone, -15 degrees) of epsilon-isorhodomycinone (epsilon-isoRMN, 6) with 1,5 anhydro-4-O-p-nitrobenzoyl-3-trifluoroacetamido-L-lyxo- (5) -L-arabino- (9) or -L ribo-hex-l-enitols (10) afforded mainly the 7-O-a-glycosyl-epsilon-isoRMNs 7, 11, and 12. Similar glycosylation of 6 with 1,5-anhydro-3-azido-4-O-p-nitrobenzoyl 2,3,6-trideoxy-L-arabino-hex-1-++ +enitol (15) yielded a-glycoside 16. Removal (M NaOH) of the p-nitrobenzoyl and trifluoroacetyl groups from 7, 11, and 12 gave the 7-O-(3-amino-2,3,6-trideoxy-a-L-hexopyranosyl)-epsilon-isoRMNs 18, 20, and 25. Reductive alkylation (CH2O, NaCNBH3) of these products afforded the 3'-N,N dimethyl analogues 22, 23, and 26. The cytotoxic effect (IC50) of the semisynthetic epsilon-isorhodomycins was tested in vitro in leukemia cell line L1210. PMID- 2224882 TI - Synthesis of O-alpha-D-glucopyranosyl-(1----4)-O-alpha -D-xylopyranosyl-(1----4) O-alpha -D-xylopyranosyl-(1----4)-D-glucopyranose as a substrate analogue of alpha amylase. AB - The tetrasaccharide a-D-Glcp-(1----4)-a-D-Xylp-(1----4)-a-D-Xylp-(1----4)-D- Glcp (1) has been synthesized, as a substrate analogue of alpha amylase, by silver perchlorate-catalyzed glycosylation of benzyl 2,3,6-tri-O-benzyl-4-O-(2,3-di-O benzyl-a-D-xylopyranosyl)-beta-D- glucopyranoside (30) with 2,3-di-O-benzyl-4-O (2,3,4,6-tetra-O-benzyl-a-D- glucopyranosyl)-a-D-xylopyranosyl chloride or by methyl triflate-promoted condensation of 30 with methyl 2,3-di-O-benzyl-4-O (2,3,4,6-tetra-O-benzyl-a-D-glucopyranosyl)-1-thio- beta-D-xylopyranoside, followed by removal of protecting groups of the resulting tetrasaccharide derivative 40. PMID- 2224883 TI - Structure of the type 5 capsular polysaccharide of Staphylococcus aureus. AB - The Staphylococcus aureus type 5 capsular polysaccharide is composed of 2 acetamido-2-deoxy-L-fucose (1 part), 2-acetamido-2-deoxy-D-fucose (1 part), and 2 acetamido-2-deoxy-D-mannuronic acid (1 part). On the basis of methylation analysis, optical rotation, high-field one- and two-dimensional 1H- and 13C n.m.r. experiments, and selective cleavage with 70% aqueous hydrogen fluoride, the polysaccharide was found to be a partially O-acetylated (50%) polymer of the repeating trisaccharide unit, [----4)-3-O-Ac-beta-D-ManpNAcA-(1----4)-a-L-FucpNAc (1----3) -beta-D-FucpNAc-(1----]n. PMID- 2224884 TI - An asymmetric approach to 2-deoxynucleosides via organosulfur building blocks as chemical chameleons. AB - An asymmetric synthesis of 6-N-benzoyl-5'-O-benzyl-2'-deoxyadenosine and its a anomer from non-carbohydrate building blocks is achieved in 7 steps. The sequence builds the basic structures using bis(methylthio)methane and methylthiomethyl phenyl sulfone as both nucleophilic and electrophilic building blocks, a feature that suggests their behavior as chemical chameleons. The asymmetric induction is achieved utilizing a kinetic resolution based upon catalytic asymmetric epoxidation. PMID- 2224885 TI - Effect on human liver glycosidases and short syntheses of 1 alpha,2 alpha,6 alpha,7 alpha,7a beta-1,2,6,7-tetrahydroxypyrrolizidine from D-glycero-D-gulo heptono-1,4-lactone. AB - The synthesis of 1 alpha,2 alpha,6 alpha,7 alpha,7a beta-1,2,6,7 tetrahydroxypyrrolizidine (1) from D-glycero-D-gulo-heptono-1,4-lactone (6) by two different routes is reported. The effects of 1 on the inhibition of 15 human liver glycosidases are described. PMID- 2224886 TI - Synthesis of 1-deoxy-6-epicastanospermine and 1-deoxy-6,8a-diepicastanospermine. AB - Extension of the carbon spine of 2,3;4,5-di-O-isopropylidene-beta-D fructopyranoside by oxidation at C-1 followed by a Wittig reaction using the phosphorane Ph3P = CHCO2Et gave an oct-4-ulose derivative, which was then transformed into the key intermediate 1-azido-1,2,3-trideoxy-D-arabino-oct-4 ulose. Catalytic hydrogenolysis of this azide, followed by reductive amination between the resulting 1-amino substituent and the 4-keto-group then gave a mixture of pyrrolidines. After sulphonylation at the terminal 8-position, the pyrrolidines were then cyclised further between the nitrogen and C-8 to give 1 deoxy-6-epicastanospermine and 1-deoxy-6,8a-diepicastanospermine. PMID- 2224887 TI - De novo synthesis of carbohydrates by stereoselective aldol reaction: L cladinose. AB - Aldol reactions of methyl 2-methoxypropanoate (4), the corresponding ester of 2 methoxypropanoic acid with 4-methyl-2,6-di-(tert-butyl)phenol (13), and silylketene acetals 14 and 15 with (S)-2-(phenyl-methoxy)propanal (17) have been investigated. The lithium enolate of 4 reacts with 17 to give primarily beta hydroxy ester 18a. If the reaction is carried out with the bis-silylketene acetal 14 under the influence of stannic chloride, beta-hydroxy acid 20c is produced. Compound 20c is cleanly inverted, via the beta-lactone 26, to provide beta hydroxy acid 19c. Compound 18a has been converted into L-cladinose by the sequence of steps: 18a----35----39----40----41----42----1. PMID- 2224888 TI - The use of N-alkoxycarbonyl derivatives of 2-amino-2-deoxy-D-glucose as donors in glycosylation reactions. AB - 1,3,4,6-Tetra-O-acetyl-2-alkoxycarbonylamino-2-deoxy-beta-D-glu copyranoses and 3,4,6-tri-O-acetyl-2-alkoxycarbonylamino-2-deoxy-alpha-D-glucopyra nosyl bromides have been used as donors in glycosylation reactions with model alcohols. beta Glycosides were obtained in good yields and with a high degree of 1,2-trans stereoselectivity. An oxazolidinone was formed as the main product from the reaction of some of the glucopyranosyl bromides with alcohols of low reactivity, but the formation of all products could be interpreted by a strong participation of the alkoxycarbonylamino group. PMID- 2224889 TI - Total synthesis of globotriaosylceramide (Gb3) and lysoglobotriaosylceramide (lysoGb3). AB - We have recently reported a highly efficient and stereocontrolled synthesis of globotriaosylceramide (Gb3, 1) in optically pure form. Key to our synthetic strategy was the implementation of the two-stage activation of thioglycosides for formation of the glycosidic bonds and the utilization of (2S, 3S, 4E)-2-azido-3-O (tert-butyldimethylsilyl)-4-octadecen-1,3-di ol (9) as a sphingosine equivalent. The syntheses of Gb3 (1) and lysoGb3 (2) were achieved by stereocontrolled coupling of 2,3,4,6-tetra-O-benzyl-alpha-D-galactosyl fluoride (15) with phenyl O (6-O-benzoyl-2,3-di-O-pivaloyl-beta-D-galactopyranosyl)- (1----4)-2,3,6-tri-O pivaloyl-1-thio-beta-D-glucopyranoside (14) to form the P kappa antigen trisaccharide masked as a phenyl 1-thioglycoside at the reducing end. Thioglycoside 16 was converted into glycosyl fluoride 19, which was coupled to 9 in high yield. The coupled product 20 was converted into the title compounds 1 and 2 in four and three steps, respectively. This article presents the total synthesis of 1 and 2 in full experimental detail. PMID- 2224890 TI - Muramic acid derivatives as glycosyl donors for the synthesis of muramyl containing glycosphingolipids and fatty acids. AB - 2-Azido-2-deoxy-4,6-O-isopropylidene-3-O-[(1R)-(methoxycarbonyl)ethyl]- alpha-D glucopyranosyl trichloroacetimidate (3 alpha) has been used as the glycosyl donor in the synthesis of glycosphingolipids 14 and 27. Reaction of 3 alpha with (2S, 3R, 4E)-2-azido-3-benzoyloxy-4-octadecen-1-ol (6) gave (2S, 3R, 4E)-2-azido-1-(2 azido-2-deoxy-4,6-O-isopropylidene-3-O-[(1R)-1-(m ethoxycarbonyl)ethyl]-beta-D glucopyranosyloxyl)-3-benzoyloxy-4- octadecene (7), which was converted into (2S, 3R, 4E)-1-(2-deoxy-2-hexadecanoylamino-3-O-[(2R)-propanoyl-(L-alanyl-D isoglutamine benzyl ester)-2-yl]-beta-D-glucopyranosyloxy)-2-hexadecanoylamino-4 oc tadecen-ol (14). Reaction of 3 alpha with tert-butyldimethylsilyl 2-azido-3,6 di-O-benzyl-2-deoxy-beta-D-glucopyranoside (15) gave tert-butyldimethylsilyl 2 azido-4-O-(2-azido-2-deoxy-4,6-O-isopropylidene-3-O-[(1R)-1-(methox ycarbonyl)ethyl]-beta-D-glucopyranosyl)-3,6-di-O-benzyl-2-deoxy-be ta- D-gluc opyranoside (16 beta), which was converted into 1,3,6-tri-O-acetyl-2-deoxy-4-O (4,6-di-O-acetyl-2-deoxy-2-hexadecanoy lam ino-3-O-[2R)-propanoyl-(L-alanyl-D isoglutamine methyl ester)-2-yl]-beta-D-glucopyranosyl)-2-hexadecanoylamino-D glucopyranose (27). PMID- 2224891 TI - Synthesis of glycopeptides with the TN and T antigen structures, and their coupling to bovine serum albumin. AB - Glycopeptides with TN and T antigen structures that represent the N-terminal tripeptide of asialoglycophorin with blood-group M specificity have been synthesized using fluorenylmethoxycarbonyl (Fmoc) and 2-pyridylethoxycarbonyl (Pyoc) groups for amino protection and the benzyl ester as the carboxyl-blocking function. The Fmoc and the Pyoc groups could be removed by treatment with the weak base morpholine under conditions where the base-sensitive O-glycosyl-serine and -threonine linkages were stable. Ester groups were removed from the carbohydrate moieties with methanolic hydrazine, to give the TN and T antigen glycopeptides which were coupled to bovine serum albumin (BSA) via a carbodi imide procedure and without any spacer groups. The resulting conjugates contained an average of greater than 20 glycopeptides per protein molecule. They are not microheterogeneous in the carbohydrate part as is commonly found for glycoproteins isolated from biological sources. PMID- 2224893 TI - Syntheses of trisaccharide C-D-E and tetrasaccharide B-C-D-E fragments found in orthosomycins. AB - 1,5-Anhydro-3-O-benzyl-2,6-dideoxy-4-O-(3,4-di-O-benzyl-2,6-dideoxy-beta -D- arabino-hexopyranosyl)-D-arabino-hex-1-enitol (17), which corresponds to the B-C fragment of various orthosomycins, was prepared from phenyl 2,3-di-O-benzyl-6 deoxy-4-O-(3,4-di-O-benzyl-2,6-dideoxy- beta-D-arabino-hexopyranosyl)-1-thio-beta D-glucopyranoside (16) by reductive lithiation. The synthesis of 16 involved a stereoselective coupling of phenyl 2,3-di-O-benzyl-6-deoxy-1-thio-beta-D glucopyranoside (9) and 1,2-di-O-acetyl-3,4-di-O-benzyl-6-deoxy-beta-D glucopyranose (14) followed by deoxygenation at C-2'. Glycosylation of methyl 2-O benzyl-6- deoxy-4-O-methyl-beta-D-galactopyranoside (25) with 3,4,6-tri-O-acetyl 2-deoxy- 2-phthalimido-beta-D-glucopyranosyl trichloroacetimidate, followed by deamination at C-2', led stereospecifically to methyl 2-O-benzyl-6-deoxy-4-O methyl-3-O-(3,4,6-tri-O-acetyl-2-deoxy-beta-D-ara bino- hexopyranosyl)-beta-D galactopyranoside (26). The 2-deoxy unit of 26 was then modified by consecutive axial introduction of a C-Me group at position 3', protection of HO-3', and deoxygenation at C-6', in order to obtain methyl 3-O-(3-O-benzoyl-2,6-dideoxy-3-C methyl-beta-D-arabino-hexopyranosyl)-2- O- benzyl-6-deoxy-4-O-methyl-beta-D galactopyranoside (39), which corresponds to the D-E fragment of orthosomycins. A glycosyloxyselenation-oxidation-elimination sequence was performed on 39 and either 1,5-anhydro-3,4-di-O-benzyl-2,6- dideoxy-D-arabino-hex-1-enitol (40) or 1,5-anhydro-3-O-benzyl-2,6-dideoxy-4-O-(3,4-di-O-benzyl-2,6- dideoxy-beta-D arabino-hexopyranosyl)-D-arabino-hex-1-enitol (17) to give the C-D-E tri-and B-C D-E tetrasaccharide fragments, respectively. Each fragment contained the spiro ortholactone junction with an (R) configuration at the anomeric carbon atom of the C-unit. PMID- 2224892 TI - 1,3,4,6-Tetra-O-acetyl-2-chloroacetamido-2-deoxy-beta-D-glucopyranose as a glycosyl donor in syntheses of oligosaccharides. AB - 1,3,4,6-Tetra-O-acetyl-2-chloroacetamido-2-deoxy-beta-D-glucopyran ose was tested as a glycosyl donor for oligosaccharide synthesis via a ferric chloride-catalyzed coupling reaction. Glycosyl acceptors tried (6 in all) were O-benzyl-protected D galactosides having free OH groups at positions 3 and 4, respectively, and similarly protected glycosides of D-glucose and 2-acetamido-2-deoxy-D-glucose unsubstituted on O-4. Existing syntheses of all the acceptors were improved, in four instances by exploitation of Garegg and Hultberg's cyanoborohydride procedure for the conversion 4,6-O-benzylidene----6- O-benzyl [Carbohydr. Res., 93 (1981) c10-c11; 108 (1982) 97-101]. Good to excellent yields of beta-linked disaccharides were obtained from the galactoside and glucoside acceptors, but with allyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranoside, stereoselectivity was lost (alpha:beta-ratio 1:2). Allyl and benzyl 2-acetamido 3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranosides gave, respectively, the allyl and benzyl beta-glycosides of the donor as major products. A mechanism is proposed for this transglycosidation reaction. The N-chloroacetyl groups in the disaccharide products were readily converted into N-acetyl by reduction with zinc acetic acid. PMID- 2224894 TI - Synthesis of L-gulose, L-galactose, and their acetylated aldehydo forms from 6-S phenyl-6-thio-D-hexoses. AB - Methyl 6-S-phenyl-6-thio-a-D-glucopyranoside, prepared in high yield from methyl a-D-glucopyranoside by the action of diphenyl disulfide and tributylphosphine in pyridine, was converted into 6-S-phenyl-6-thio-D-glucitol pentaacetate (7) by sequential hydrolysis, borohydride reduction, and acetylation. Oxidation of 7 with 3-chloroperoxybenzoic acid gave the corresponding S-epimeric sulfoxides, which underwent Pummerer rearrangement to 1-epimeric L-gulose S-phenyl monothiohemiacetal hexaacetates. Boron trifluoride-catalyzed reaction of the latter with thiophenol gave the analogous diphenyl dithioacetal, whereas base catalyzed methanolysis led to free L-gulose. Treatment of 7 with N chlorosuccinimide afforded 1-epimeric 1-chloro-1-S-phenyl-1-thio-L-gulitol pentaacetates, which were hydrolyzed to provide aldehydo-L-gulose pentaacetate. The same reaction sequences were performed with 6-S-phenyl-6-thio-D-galactose, synthesized in two steps from 1,2:3,4-di-O-isopropylidene-a-D-galactopyranose, furnishing ultimately L-galactose, its diphenyl dithioacetal pentaacetate, and aldehydo-L-galactose pentaacetate. Similar reaction sequences for the chain terminal interchange of oxidation state in other omega-S-phenyl-omega-thioaldoses may prove useful for the preparation of less-common sugar derivatives. PMID- 2224895 TI - Multiple and long-range participation of benzyl groups in intramolecular C arylation reactions of benzylated glycosides. AB - The intrinsic reactivity of furanosides bearing activated O-benzyl substituents (3-methoxybenzyl), in the presence of bidentate Lewis acids such as tin(IV) chloride, was explored. These glycosides were found to exhibit extremely interesting chemical properties. Thus, with three reactive substituents (at O 2,3,5), the corresponding glycosides (1 and 7) underwent a novel internal bis-C arylation process, which involved successive alkylations of the benzyl groups at O-2 and O-3 ("multiple participation"), leading to the formal replacement of the two C-O bonds at the anomeric center of the glycoside by two C-C bonds. The bis-C arylated constitution of the resulting polycyclic compounds 4 and 8, and the cis configuration of their fused ring system (a tetrahydro-[2]benzopyrano[3,4 d][2]benzoxepin derivative), were determined on the basis of their n.m.r. spectral parameters. With two 3-methoxybenzyl substituents (at O-3 and O-5, compound 6), intramolecular alkylation of the benzyl group at O-3 or O-5 occurred when glycoside 6 was reacted with titanium(IV) chloride or tin(IV) chloride, respectively, thereby leading to novel bicyclic internal aryl C-glycosides (9 and 12) as major products ("long-range participation"). The constitution of compounds 9 and 12 was unambiguously established by the reactions of analogs of 6 bearing only one 3-methoxybenzyl substituent at a specific position (at O-3: 15; at O-5: 20). The unexpected divergent behavior of 6 in the presence of titanium(IV) and tin(IV) chloride remains to be explained. The availability of compound 9 made it possible to independently prepare the bis-C-arylated derivative 8 (by way of the reverse sequence of internal C-arylation reactions) and thereby to definitively demonstrate its constitution. These unprecedented reactions extend the scope of the intramolecular C-glycosidation of substituted sugars and provide novel methodologies in synthetic carbohydrate chemistry. PMID- 2224896 TI - Synthesis of methyl 3-O-alpha-D-galactopyranosyl-6-O-alpha-D-mannopyranosyl- alpha-D-mannopyranoside, methyl 3-O-alpha-D-glucopyranosyl-6-O-alpha-D- mannopyranosyl-alpha-D-mannopyranoside, methyl 6-O-alpha-D-galactopyranosyl-3- O alpha-D-mannopyranosyl-alpha-D-mannopyranoside, and methyl 6-O-alpha-D glucopyranosyl-3-O-alpha-D-mannopyranosyl-alpha-D- mannopyranoside. PMID- 2224897 TI - Separation of yeast asparagine-linked oligosaccharides by high-performance anion exchange chromatography. AB - Oligosaccharides obtained from Saccharomyces cerevisiae mannoproteins by digestion with endo-N-acetyl-beta-D-glucosaminidase H were fractionated by anion exchange chromatography, by elution with 50-100mM NaOH without or with a sodium acetate gradient, and detected with a pulsed amperometric detector (PAD). The elution times of homologous oligosaccharides fell on a straight line having a slope characteristic of the structural type. The response of the PAD detector per mole of oligosaccharide increased about 2-fold going from Man3GlcNAc to Man13GlcNAc, and appeared to depend primarily on the oxidation of the reducing end N-acetylglucosamine unit common to all the oligosaccharides. The digestion of a Man10GlcNAc with jack-bean alpha-mannosidase was monitored by injecting portions of the crude reaction mixture, and the intermediates were characterized by their elution positions and n.m.r. spectra in the anomeric proton region. One commercial jack-bean alpha-mannosidase preparation contained a novel endolytic activity that released N-acetylglucosamine from the reducing ends of the oligosaccharides and was shown to convert P----6 alpha Man----6 alpha Man----6 beta Man----4 alpha beta GlcNAc to P----6 alpha Man----6 alpha Man----6 alpha beta Man plus free N-acetylglucosamine. Another commercial jack-bean alpha mannosidase converted the Man10GlcNAc to a Man3GlcNAc having the structure alpha Man----6 beta Man----4 alpha beta GlcNAc, [formula: see text] whereas the Oerskovia sp. alpha-mannosidase converted the same oligosaccharide to a Man4GlcNAc having the structure alpha Man----6 alpha Man----6 beta Man----4 alpha beta GlcNAc. [formula: see text] PMID- 2224898 TI - Structure of an exocellular beta-D-glucan from Pediococcus sp., a wine lactic bacteria. AB - Pediococcus sp. produces an exocellular slime containing exclusively D-glucose. The structure of the polysaccharide was determined by methylation analysis, Smith degradation, enzymic hydrolysis, and 13C-n.m.r. spectroscopy as having a trisaccharide repeating unit, ----3)-beta-D-Glcp-(1---- 3)-[beta-D-Glcp-(1----2)] beta-D-Glcp-(1----. PMID- 2224899 TI - Alteration of the properties of Aspergillus sp. K-27 glucoamylase on limited proteolysis with subtilisin. AB - An active derivative (mol. wt. 48,000) of Aspergillus sp. K-27 glucoamylase (mol. wt. 76,000) was obtained by limited proteolysis with subtilisin. The amino acid sequences of native and modified enzymes at the N-termini were Ala-Gly-Gly-Thr Leu-Asp and Ala-Val-Leu, respectively. The proteolysis greatly decreased the affinity of the enzyme for amylopectin and glycogen, but not for oligosaccharides. It also reduced the ability of the enzyme to degrade raw starch, abolished the ability of the enzyme to adsorb onto starch granules, and eliminated the synergistic action of the enzyme in the hydrolysis of starch granules with alpha-amylase. These findings imply that the enzyme has a specific affinity site for polysaccharide substrates besides the catalytic site, i.e., a starch-binding site, and that the former is removed by proteolysis. The extent of the reduction in the activity for raw starches caused by the modification varied with the starch source, as the modified enzyme digested raw potato starch better than either raw corn or sweet potato starches. A new method for evaluation of the raw starch-digesting activity of glucoamylase is described. PMID- 2224900 TI - Uncertainties in structural determinations of oligosaccharide conformation, using measurements of nuclear Overhauser effects. AB - A fundamental problem in the determination of molecular structure by n.m.r. spectroscopy is insufficient experimental constraints. This problem is particularly marked for oligosaccharides, where few constraints are available across glycosidic linkages. By calculating distances as a function of dihedral angle, it is shown that, in general, two n.O.e. constraints result in two possible conformations for each glycosidic linkage, one of which can usually be discarded on the basis of model building or energy calculations. Using these calculations, an estimate of the uncertainty in the structure can be obtained. PMID- 2224901 TI - Synthesis of methyl O-(2-O-methyl-beta-D-galactopyranosyl)-(1----4)-O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-beta-D- galactopyranoside and 4 nitrophenyl O-beta-D-galactopyranosyl-(1----4)-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----3)-beta-D-galactopyranoside. PMID- 2224902 TI - Synthesis of benzyl O-(2-O-methyl-beta-D-galactopyranosyl)-(1----3)-2- acetamido 2-deoxy-beta-D-glucopyranoside [benzyl 2'-O-methyllacto-N-bioside I], and its higher saccharide containing an O-(2-O-methyl-beta-D- galactopyranosyl)-(1----3) 2-acetamido-2-deoxy-beta-D-glucopyranosyl group as a potential substrate for (1-- 4)-alpha-L-fucosyltransferase. AB - Treatment of benzyl O-beta-D-galactopyranosyl-(1----3)-2-acetamido-2- deoxy-4,6-O isopropylidene-beta-D-glucopyranoside with tert-butylchlorodiphenylsilane afforded the 6'-O-tert-butyldiphenylsilyl ether, which was converted into the 3',4'-O-isopropylidene derivative. Methylation and subsequent removal of protecting groups afforded benzyl O-(2-O-methyl-beta-D-galactopyranosyl)- (1--- 3)-2-acetamido-2-deoxy-beta-D-glucopyranoside (7). The trisaccharide methyl O-(2 O-methyl-beta-D-galactopyranosyl)-(1----3)-O-(2- acetamido-2-deoxy-beta-D glucopyranosyl)-(1----3)-beta-D-galactopyranosi de (17) and the tetrasaccharide O (2-O-methyl-beta-D-galactopyranosyl)-(1----3)-O-(2-acetamido-2-deoxy-b eta-D- glucopyranosyl)-(1----3)-O-beta-D-galactopyranosyl-(1----4)-D-glucopyran ose (32), both containing the 2'-O-methyllacto-N-biose I unit at the nonreducing end, were synthesized, and the structures of 7, 17, and 32 were confirmed by 13C n.m.r. spectroscopy. PMID- 2224903 TI - High-pressure glycosylations of unreactive alcohols and the formation of N glycosyl collidinium salts. AB - The yields of disaccharide glycosylation products in tetramethylammonium bromide or silver triflate-collidine activated reactions between hindered alcohols and glycosyl halides were not greatly ++affected when a pressure of 15 kbar was applied. The formation of orthoester products was greatly increased under pressure. When orthoester formation was not possible both disaccharides and the related N-glycosyl collidinium salts were found. PMID- 2224904 TI - Enzymic synthesis of useful chito-oligosaccharides utilizing transglycosylation by chitinolytic enzymes in a buffer containing ammonium sulfate. AB - A chitinase purified from culture filtrates of Trichoderma resei KDR-11 efficiently catalyzed a transglycosylation reaction on tetra-N acetylchitotetraoside in a buffer medium containing ammonium sulfate, converting the tetrasaccharide into hexa-N-acetylchitohexaose (39.6%) and di-N acetylchitobiose (55.7%) as the major products. Sugar-chain elongation from di-N acetylchitobiose as the initial substrate to hexa-N-acetyl-chitohexaose and hepta N-acetylchitoheptaose was also efficiently induced through lysozyme catalysis in the presence of ammonium sulfate at high (30%) concentration. In this case, the addition of ammonium sulfate to the reaction system resulted in a remarkable increase of the hexamer and heptamer productions, which are desirable as biologically active oligosaccharides. PMID- 2224905 TI - Isolation and analysis by the reductive-cleavage method of linkage positions and ring forms in the Mycobacterium smegmatis cell-wall arabinogalactan. AB - The Mycobacterium smegmatis arabinogalactan polysaccharide has been isolated from the cell wall by saponification and extraction to remove lipids and subsequent solubilization by treatment with lysozyme. Analysis for neutral sugars demonstrated the presence of D-arabinose and D-galactose in a ratio of 3:1, respectively. Reductive cleavage of the fully methylated polysaccharide in the presence of triethylsilane and trimethylsilyl trifluoromethanesulfonate and subsequent acetylation in situ gave six partially methylated 1,4-anhydroalditol acetates as the major products and three partially methylated 1,5-anhydroalditol acetates as minor products. Partially methylated 1,5-anhydroalditol acetates were not formed when reductive cleavage was accomplished with triethylsilane and a mixture of trimethylsilyl methanesulfonate and boron trifluoride etherate as the catalyst, demonstrating that the polysaccharide is exclusively comprised of furanosyl residues. The partially methylated anhydroalditols so produced were identified by comparison to authentic standards. Their identifies are consistent with the presence in the M. smegmatis arabinogalactan of an octasaccharide repeating unit comprised of a nonreducing terminal D-arabinofuranosyl group, a 2 O-linked D-arabinofuranosyl residue, three 5-O-linked D-arabinofuranosyl residues, a 3,5-di-O-linked D-arabinofuranosyl residue, a 5-O-linked D galactofuranosyl residue, and a 6-O-linked D-galactofuranosyl residue. PMID- 2224906 TI - Lymphoproliferative diseases in disorders of the immune system. AB - Severe immunodeficiency diseases are complicated by the development of malignancies of the immune system itself, mainly non-Hodgkin's lymphoma (NHLs). These occur in immunosuppressed organ allograft recipients; in cancer chemotherapy patients; in patients with primary immunodeficiency diseases; in chronic dialysis patients; in victims of the Acquired Immunodeficiency Syndrome (AIDS); and in persons with various autoimmune diseases either untreated or given immunosuppressive therapy. Most of these NHLs are reticulum cell sarcomas or immunoblastic sarcomas. Immunologically, most are of B-cell origin. Most tumors are extranodal in distribution. They show a remarkable predilection for the brain. Possible causes of the NHLs include oncogenic viruses; disturbed immune surveillance; chronic antigenic stimulation; impaired immunoregulation; carcinogenic effects of immunosuppressive, cytotoxic or other drugs; and genetic susceptibility to lymphomagenesis. PMID- 2224907 TI - Pathoepidemiological features of adult T-cell lymphoma/leukemia in an endemic area: Kagoshima, Japan. AB - In order to elucidate the pathological and epidemiological features of malignant lymphoma (ML), particularly of adult T-cell lymphoma/leukemia (ATLL) in the Kagoshima district, age-adjusted and age-specific incidence rates of malignant lymphomas were estimated on 3239 histologically confirmed cases between the years 1963 and 1987. There was a marked increase in the incidence rate from 1976 (4.9) to 1982 (8.5) due to the increase of T-cell lymphomas. The increase was not conspicuous after 1982. Immunohistochemically, all of the 429 MLs found in 1985 and 1986 were examined on paraffin sections and 70 ATLL cases on fresh frozen sections. T-cell ML comprised 65.3%, B-cell ML 30.5%, Hodgkin disease 2.6%, and histiocytic ML 1.2%. Most of ATLL cells were phenotypically CD4+ CD8-, 14% of ATLL cases showed CD4+ CD8+, 6% were CD4- CD8+, and 7% were CD4- CD8-. The simulataneous expression of IL 2 and IL 2R was seen in 8 (16%) out of 56 patients examined. Therefore, a proliferation by autocrine mechanism does not seem to be a major course of ATLL progression. PMID- 2224908 TI - Detection of preleukemic state of adult T-cell leukemia (pre-ATL) in HTLV-1 carriers. AB - The prevalence of the preleukemic state of adult T-cell leukemia (pre-ATL) was studied in Nagasaki prefecture, one of the endemic human T-lymphotropic virus type 1 (HTLV-1) areas in Japan. Pre-ATL cases have the monoclonal proliferation of abnormal lymphocytes, without signs of malignant proliferation or clinical signs and symptoms related to leukemia. HTLV-1 carriers who have monoclonal integration of HTLV-1 proviral DNA may be at high risk of developing ATL. Abnormal lymphocytes with either bilobular or large and chromatin-rich nuclei were found in 63/356 (17.7%) of HTLV-1 carriers among inhabitants. We analyzed DNA of peripheral lymphocytes from 108 carries with abnormal lymphocytes by Southern blot technique. Monoclonal integration of HTLV-1 has been detected in 12 cases (11.1%). These results lead to the conclusion that the prevalence rate of pre-ATL among all HTLV-1 carriers is about 2%. Pre-ATL is presumed to be the clinical stage which precedes ATL, although the possibility remains that the HTLV 1 carrier may develop symptoms of ATL directly, without going through the pre-ATL stage. PMID- 2224909 TI - Viral oncogenesis and the immune system. AB - Oncogenic transformation of normal cells and the establishment of transformed cells to form malignant tumors is a complex, multistep process influenced by viruses in multiple ways. The relationship between viruses and the immune system manifests itself, in part, through various roles of viruses in transformation of host cells, including cells of the immune system. A large number of viruses participate in oncogenic transformation of cells in many animal species. Candidates for oncogenic transformation in man are human T lymphotropic viruses I and II, certain human papillomavirus types, hepatitis B virus, and Epstein-Barr virus. Various mechanisms, which may overlap with one another, have been proposed to account for viral oncogenesis. These include introduction of a directly transforming viral gene, retroviral transduction of protooncogenes, mutagenesis, uncoupling of cellular protooncogene expression from normal regulatory controls, overexpression of normal cellular genes resulting from effects of viral cis- or trans-acting factors, and inactivation of tumor suppressor genes. A second critical area of interaction between viruses and the immune system is in the selection of transformed cells. When cell transformation is accompanied by expression of tumor antigens, the immune system may influence tumor cell establishment and selection of transformed cells for metastatic outgrowth. Finally, host well-being may be severely compromised when viruses infect cells of the immune system, leading to an inability to mount immunological responses specific for opportunistic microorganisms and for cells transformed by viruses or nonviral agents. Human immunodeficiency virus infection exemplifies this phenomenon, although other viruses also negatively affect the immune system. The role of normal immune responses in limiting tumor cell growth is evident from the increased incidence of malignancies in immunocompromised hosts. PMID- 2224911 TI - Immunogenicity of the tumor determines the outcome of immunotherapy with interleukin-2, ABPP, and cyclophosphamide of micro- and macrometastatic intraperitoneal tumor. AB - We have shown previously that interleukin-2 (IL-2) and the interferon inducer ABPP can induce lymphokine activated killer (LAK) cell activity in vivo after intraperitoneal (i.p.) administration. The antitumor effects of various immunotherapy regimens with IL-2, LAK cells, ABPP, and cyclophosphamide (CY) on microscopic (day 3) and on macroscopic (day 8) i.p. tumors, differing in histology and immunogenicity, were studied in C57BL6 mice. The immunogenic sarcomas MCA-105, -106, and the colon adenocarcinoma MCA-38, and the nonimmunogenic sarcomas MCA-101, -102 were used. After i.p. inoculation of 1 X 10(5) tumor cells i.p. on day 0, therapy with IL-2 +/- LAK cells consisted of 1 X 10(8) LAK cells, i.p., on day 3 and IL-2, 10k to 25k U, i.p., b.i.d., on days 3 to 7. Treatment with ABPP +/- CY consisted of CY, 50 mg/kg, i.p., on day 3 and/or 8 ABPP, 250 mg/kg on days 3, 4 and/or 8, 9. In the treatment of micrometastases, IL-2 + LAK cell therapy was effective against all tumors. Therapy with low dose IL-2 alone was effective only against immunogenic tumors. Combined therapy with CY was very effective against the immunogenic tumors and prolonged survival significantly. Only marginal antitumor effects were seen against nonimmunogenic tumors. In the setting of advanced tumor, chemoimmunotherapy was only successful against immunogenic tumors. These observations demonstrate that the immunogenicity of the tumor is of major importance in the outcome of immunotherapy, especially in the setting of advanced disease. This indicates that, apart from LAK cells, the in vivo activation of other cytotoxic effector cells is important in the rejection of immunogenic tumors. PMID- 2224910 TI - Tumor-cytolytic human macrophages cultured as nonadherent cells: potential for the adoptive immunotherapy of cancer. AB - Tumor-cytolytic lymphokine (e.g., interleukin-2; IL-2)-activated killer cells are currently being evaluated in IL-2/LAK cell adoptive immunotherapy regimens for the treatment of cancer. Monocyte-derived macrophages (M phi) are also known to be efficient tumor killer cells; accordingly, M phi that have been activated in vitro may also be of therapeutic merit. However, attempts to cultivate M phi for morphological and functional studies have often been compromised because M phi adhere rapidly and tenaciously to cultureware. Studies that we have conducted to address this problem have proven successful in developing procedures for the long term cultivation of non-adherent immunocompetent M phi in serum-free medium using petri dishes containing a thin Teflon liner. The utility of this technology is documented by the results of studies presented herein in which light and scanning electron microscopy was used to analyze tumor-cytolytic human M phi. In these experiments, we demonstrated that nonadherent immunocompetent human M phi can be prepared for detailed examinations of their pleomorphic membrane architecture. Moreover, nonadherent human M phi could readily be collected for preparing conjugates of M phi and tumor cells. It is anticipated that this technology should prove useful for future structure-function studies defining the topographical location and spatial distribution of antigens and receptors on M phi membrane ultrastructures, particularly the microvilli-like projections that bridge together an immunocompetent effector M phi and target cell (e.g., tumor cells and microbial pathogens) and which provide the physical interaction required for the initial phases of a cellular immune response that includes antigen recognition and cell-to-cell adhesion. PMID- 2224912 TI - Clinical evaluation of liposomal tumor antigen vaccines in patients with stage III melanoma. AB - In this study, we report the results of an active-specific immunotherapy phase I study using autologous tumor-associated antigens (TAA) incorporated within liposomal carriers in patients with metastatic malignant melanoma. A group of 13 patients were entered into the study and given subcutaneous (s.c.) injections of liposome-TAA preparations at 2- to 4-week intervals. Clinical and laboratory monitoring did not reveal any short- or long-term systemic or local toxicity. Three patients had a complete response, and two patients had a partial response (50% or greater size reduction in one or more tumor sites). The remaining eight patients showed no response with disease progression. Two of these eight patients are still undergoing treatment. The TAA preparations stimulated peripheral blood lymphocyte proliferation (PBL) in vitro in those patients exhibiting a clinical response: no such responses were observed in the nonresponder patients. NK cell activity did not correlate with PBL proliferation or clinical response status, whereas PBL cytostatic activity against heterologous melanoma tumor cells correlated with clinical responsiveness. This form of immunotherapy appears to be a safe and feasible candidate for a much larger phase I/II study. PMID- 2224913 TI - The impact of passive smoking: cancer deaths among nonsmoking women. AB - In order to obtain an estimate of the impact of passive smoking on cancer mortality, a retrospective study was conducted examining the cancer mortality of nonsmoking wives with no known or minimal exposure in contrast to nonsmoking wives with moderate to life-time exposure to tobacco smoke. The study was based on the data from 906 deceased nonsmoking women who resided in Erie County, Pennsylvania, who were divided into the following three categories: 1. No known exposure. 2. Exposed nonemployed. 3. Employed (assumed to be exposed to environmental tobacco smoke in the workplace). The data were analyzed by the retrospective case-control method using cancer deaths as the cases and non-cancer related deaths as the controls. Also, the data from 401 smoking women were used for comparative purposes of the total percentage of cancer deaths among three groups: 1. Nonsmoking, nonexposed women. 2. Combined nonsmoking unemployed and employed exposed women. 3. Smoking women. The major findings from the study are: 1. Only (2.2%) of the total deaths reported among the nonsmoking women with no known or minimal exposure to tobacco smoke were due to cancer of any site. 2. No cases of lung cancer deaths were reported for the nonexposed, nonsmoking women, and eight lung cancer deaths were reported among the nonsmoking women who were exposed to passive smoking. Also, for this small group of 170 nonsmoking nonexposed women, there were no reported cases of breast cancer, genitourinary or lymphatic cancer. 3. Employed nonsmoking women experienced proportionately more cancer deaths (34.3%) than both nonexposed (2.2%) and exposed nonemployed wives (18.9%). The combined groups of exposed nonsmoking wives (nonemployed and employed) contracted 25.5% cancer deaths. 4. Age-adjusted data showed similar trends. 5. Cancer death rates for women smokers was 35.5% of the total deaths of women smokers. Public health officials should consider requiring that the workplace be free from tobacco smoke since these data imply that passive smoking has a very detrimental effect upon nonsmokers. Also, smokers should be made aware of the potential damage they inflict on others in their home as well as the workplace. PMID- 2224914 TI - Theoretical and experimentally quantifiable determinants of tobacco smoking behavior for the development of successful smoking cessation strategies. AB - Death rates from a number of diseases linked epidemiologically to tobacco use continue to rise despite major reductions in per capita tobacco consumption, despite reductions in the total number of smokers, and despite very significant reductions in "tar", in other tumorigens and in essentially all classes of potential toxins in smoke delivered to the consumer. One concern is that smokers consume low delivery cigarettes differently and in a potentially more hazardous way than higher delivery cigarettes. The effect of nicotine reduction in cigarettes on human smoking behavior was studied in 102 human subjects by quantifiable determinants of tobacco-smoking behavior. This study indicates that reduction in nicotine delivery results in some accommodation in smoking behavior to titrate nicotine needs. In addition, smokers appear to adjust their smoking behavior as a function of taste preference, and this adjustment is as strong as the accommodation for nicotine. The theoretical application of these observations to the development of successful smoking cessation strategies is reviewed. PMID- 2224915 TI - "Tar", nicotine, and carbon monoxide content of Thai cigarettes, and implications for cancer prevention in Thailand. AB - This report presents new findings on the very high contents of nicotine (i.e., 1.64 to 5.77 mg) and "tar" (i.e., 21.3 to 28.1 mg) in major brands of commercially produced Thai cigarettes and local tobacco used for rolled cigarettes. These nicotine levels are relevant to the addictive properties of Thai cigarettes, while the "tar" levels are related to risk of cancer of the lung and other sites. Consumption of tobacco products nearly tripled over the last 2 decades (1966 to 1987). The relative frequency of lung cancer in Thailand in 1982 was high in both urban and rural areas, with geographic differences particularly for females, and increased from 1975 to 1982 in both males and females. The important implications of cigarette contents and consumption are presented in relation to future cancer patterns and cancer prevention in Thailand. Labeling of cigarettes, in terms of "tar" and nicotine contents is needed along with educational programs dealing with the harmful and addictive effects of these substances. PMID- 2224916 TI - Chemoprevention for lung cancer--evidence for a high degree of compliance. AB - Studies of treatment efficacy are important for the development of cancer chemoprevention strategies. Recruitment aims for motivated, compliant subjects. The Concerned Smoker Study targets smokers with at least a 15-pack-year history and bronchial atypia on sputum sampling. Subjects receive etretinate 25 mg daily or identical placebo and are followed for 6 months. Compliance was monitored by assessing timely return for follow-up visits, return of monthly sputum samples, pill counts, and serum etretinate levels. Contamination, in the control group, was assessed by measuring etretinate levels. With half of the subjects having completed the study, this report assesses compliance: 88% follow-up visits occurred on schedule with only 9 missed visits of a possible total of 380; 443 (97.1%) of 456 possible sputum samples were returned. Pill counts indicated a high degree of compliance which was supported by the serum etretinate levels. Contamination was insignificant. The results suggest a very high degree of compliance. Only minor protocol changes will be required. PMID- 2224917 TI - Chromosome abnormalities in cancer. AB - Karyotypic abnormalities have been described in more than 10,000 human neoplasms analyzed by means of chromosome banding. These aberrations are of three different kinds: primary abnormalities, which are essential in establishing the tumor; secondary abnormalities, which develop only after the neoplasm is established but which nevertheless may be important in tumor progression; and cytogenetic noise, which is the background level of nonconsequential aberrations. These latter changes are, in contrast to the primary and secondary aberrations, randomly distributed throughout the genome. The primary abnormalities, of which more than 100 have been identified, are strictly correlated with particular neoplastic disorders and even with histopathological subgroups within a given tumor type. To these purely cytogenetic data implicating specific genetic changes in carcinogenesis may now be added the growing evidence of molecular specificity emerging from recombinant DNA studies. It appears that both currently known classes of directly cancer-relevant genes, the dominant oncogenes and the recessive anti-oncogenes, are located at precisely those genomic sites that are visibly involved in neoplasia-associated chromosomal rearrangements. The molecular genetic data thus support the cytogenetic conclusion that the distribution of consistently cancer-associated breakpoints reflects the genomic position of genes that, either directly or through the control function they exert, are essential in the proliferation and differentiation of human cells. PMID- 2224918 TI - Cancer genetics and cancer suppression. AB - Identification of normal growth and differentiation-inducing proteins and how they interact in normal development has made it possible to identify the molecular basis of normal development and the mechanisms that uncouple growth and differentiation so as to produce malignant cells. When normal cells have been changed into cancer cells, the malignant phenotype can again be suppressed. Results on the molecular control of growth and differentiation in normal myeloid hematopoietic cells, changes in the normal developmental program in myeloid leukemia, and the suppression of malignancy in myeloid leukemia and sarcomas have shown that (1) malignancy can be suppressed either with or without genetic changes in the malignant cells, (2) suppression of malignancy by inducing differentiation does not have to restore all the normal controls, and (3) genetic abnormalities which give rise to malignancy can be bypassed and their effects nullified by inducing differentiation which stops cells from multiplying. PMID- 2224919 TI - Cancer incidence in young offspring of Jewish immigrants to Israel. A methodological study. I. Nasopharyngeal malignancies and Ewing sarcoma. AB - Differences in cancer incidence among various immigrant groups in Israel raised the question of persistence in their descendants. The methodological problems of identification of both parents and their origins, the choice of the denominator, and the long period of observation necessary for the rare childhood tumors have been examined. From 22-years data of the Israel Cancer Registry (ICR), three malignancies were chosen as examples: epithelial carcinoma of nasopharynx (31 cases), non-Hodgkin's lymphoma of nasopharynx (14 cases), and Ewing sarcoma (55 cases). The actual number of cases, in spite of the long period of incidence, is small and the computed significance must be accepted with reservation. There are two outstanding findings: the higher incidence in males as well as in females for nasopharynx carcinoma corresponds to that of their African-born parents; an increasing trend in the second 11-years period for Ewing sarcoma. Similar studies on leukemias, lymphomas, and others with a greater number of cases can be expected to have more reliable results. This survey relied on the majority of patients with immigrant parents, mostly of the same origin. In the following years, second and later generations of Israel-born and an increasing part of intermarriages will severely impede similar studies. PMID- 2224920 TI - Dietary, total body, and intracellular potassium-to-sodium ratios and their influence on cancer. AB - One of the greatest changes in the human diet, a change that has occurred only within the past few thousand years, is the immense increase in the intake of sodium (Na) caused by use of table salt in the preparation and preservation of food. At the same time, man's intake of potassium (K) has decreased. The result is that from Paleolithic times to modern times the dietary K/Na ratio has been reduced by a factor of about 20. Based on a comparison of modern people in civilized areas with the primitive Yanomamo Indians in South America (who do not eat salt but who do grow and eat potassium-rich cooking bananas), this factor may even be on the order of 100 to 200. Humans, who initially had to adapt to retain sodium from a sodium-poor diet and to excrete potassium from a potassium-rich diet, have not yet evolutionarily adapted to today's high-sodium, low-potassium diet. This failure has caused increased rates of a number of diseases in civilized man, among them cancer. The influence of the K/Na ratio on cancer development--first discovered by epidemiologic studies--has been confirmed by various means, such as dietary studies, gerontological studies, studies of relationships between hyper- and hypokalemic diseases and cancer, and review of the cellular changes of this ratio induced by carcinogenic and anticarcinogenic agents. Recently, animal experiments have also confirmed the results. The recommended dietary K/Na ratio should be well above 1, preferably 5 or higher, and the cellular K/Na ratio should be above 10. PMID- 2224921 TI - Nutrition and lifestyle factors in fibrocystic disease and cancer of the breast. AB - Within a study on diet as a risk factor for fibrocystic disease and breast cancer, 68 patients with breast cancer, aged from 40 to 59, participating in the National Breast Screening Study in Montreal, were compared to 340 patients with fibrocystic disease and to 343 controls. The personal and family history was collected from medical records and completed by an interview. The nutritional assessment was done by a food frequency questionnaire with a special attention to the quantity and quality of fat, vitamins A, C, E, as well as life style habits. The cancer patients were significantly heavier (64.9 vs. 60.8 kg), had higher body mass index (24.9 vs. 23.4), menstrual cycle more often irregular, later menopause (47.5 vs. 44.5 years), and shorter school attendance (10.3 vs. 12.6 years). No significant differences were found in the use of contraceptives, menopausal hormones, analgesics and tobacco, marital status, number of pregnancies and children, age at menarche, duration of menstrual cycle, and the age at the first pregnancy. The cancer patients consumed significantly more poultry, fish, pastry, margarine, and alcohol and less milk, raw vegetables, pastas, sugar, butter, and coffee. PMID- 2224922 TI - Breast screening compliance following a statewide low-cost mammography project. AB - Public health educational campaigns can attract large numbers of one-time participants, but the impact on subsequent behavior remains unstudied. The American Cancer Society Texas Division, Inc. sponsored a statewide $50.00 mammography screening project in early 1987. More than 64,000 mammograms were completed at 306 centers; 37,000 screenees answered a 31-item questionnaire. Attitudes toward screening were assessed, and screening history was recorded. Eighteen months after the project, a follow-up questionnaire was sent to 1000 screenees; 411 women returned the questionnaires. In the year following the project, 51% of the women 50 years and older reported having a subsequent mammogram. Among the women in this group who had never had a mammogram prior to 1987, 42% had screening mammography repeated in the following year. These data show that media-based public education projects can be effective mechanisms for improving and maintaining compliance with mammography screening recommendations. PMID- 2224923 TI - The effect of mild stress on DMH-induced colorectal cancer. AB - Epidemiologic studies suggest that certain psychosocial factors increase the risk of cancer. Yet, animal studies suggest that psychosocial stress inhibits the development of chemically induced tumorigenesis. The purpose of this study was to examine the effect of three different chronic mild stressors on the development of dimethylhydrazine (DMH)-induced colorectal carcinoma in rats. Results of this study show that the development of DMH-induced colorectal carcinoma was not significantly inhibited or altered by each individual stress treatment. Additionally, results indicate that mild stressors can induce neurochemical changes commonly associated with stress, without the confounding effects of more aversive stressors that are likely to compromise the nutritional and physiological status of the animal and thereby alter tumor formation. PMID- 2224924 TI - In vitro ultrastructural localization of the catalytic activity of adenosine deaminase in murine C-1300 neuroblastoma. AB - Adenosine deaminase (ADA) activity was localized at the surface membrane of the mouse C-1300 neuroblastoma by incubation of a confluent tissue culture monolayer grown on Lux-Permanox cultureware with 6-chloropurine ribonucleoside (CPR). This substrate is dechlorinated by ADA to form Cl-. At loci of ADA activity, Cl- is precipitated with added silver ion (Ag+), and electron dense metallic silver (Ag degree) is formed upon exposure to light. The incubation was conducted in 0.2 M HEPES buffer (277 mOs) at 37 degrees C, pH 7.4, which contained 1 mM CPR, for 5 min (in this buffer, this is four times the Km); the control lacked the substrate. After completion of the incubation, the monolayer was briefly rinsed with 0.2 M HEPES and 2.5% glutaraldehyde in 0.2 M HEPES containing AgNO3 at a final concentration of 2 mM. Dehydration was accomplished in a graded series of ethanol followed by embedment in the L. R. White resin at 60 degrees C overnight. Thin sections (80 to 100 mm), cut parallel to the monolayer, showed ADA activity at the cells' surface membrane with a smaller amount of activity evenly distributed in the subadjacent ectoplasmic zone. The control lacked any silver grain localization. Since in preliminary studies of neuronal tissue the ADA activity was minimal, these findings may contribute to developing a diagnostic cancer screening test. PMID- 2224925 TI - Cardiovascular response to exercise. PMID- 2224926 TI - Intracoronary adenosine causes angina pectoris like pain--an inquiry into the nature of visceral pain. AB - STUDY OBJECTIVE: The aim was to study the tentative role of adenosine as a messenger between myocardial ischaemia and angina pectoris. DESIGN: Adenosine was administered in serial doses of 0.1-20 mg either as an intravenous bolus, or intra-arterially over 10 s into the left coronary artery, the aorta and the iliac artery. Coronary sinus flow was determined by thermodilution. ECG was monitored continuously. The patient was not aware of which site or dose was used. After each injection, the start of, maximum, end, magnitude, and location of pain were noted. PATIENTS: Six patients with angina pectoris referred for coronary angiography entered the study. MEASUREMENTS AND RESULTS: After intracoronary adenosine injection in the absence of ischaemic ECG changes, a dose dependent degree of chest pain was experienced not different in quality or location from the patients' habitual angina pectoris. Adenosine into the aorta provoked pain in lower chest and upper abdomen, whereas injection into the iliac artery provoked pain in the ipsilateral leg. On intravenous injection equipotent doses of adenosine caused chest pain of the same degree and quality as after intracoronary injection. Immediately after intracoronary injection the coronary sinus blood flow started to increase, but the onset of chest pain was delayed. Onset of pain was earlier the higher the dose, the maximum dose resulting in onset after 18(SEM 2) s. Coronary sinus blood flow increased dose dependently after left coronary artery injection but following intravenous injection no further increase was seen beyond that induced by the lowest dose. CONCLUSIONS: We suggest that adenosine is an important messenger for the sensation of angina pectoris and the effect is not due to coronary steal leading to myocardial ischaemia. PMID- 2224927 TI - Different histamine actions in proximal and distal human coronary arteries in vitro. AB - STUDY OBJECTIVE: The aim was to investigate the receptor mechanisms for different histamine actions in proximal and distal human coronary arteries. DESIGN: Postmortem human coronary rings precontracted by 50 mM KCl were exposed to histamine (10(-8)-10(-4) M) in control and after treatment with 10(-5) M pyrilamine (an H1 receptor antagonist), or 10(-4) M cimetidine (an H2 receptor antagonist), and/or endothelial removal. Tension changes at the point of maximum relaxation (at 10(-5) M in most rings) were obtained. MEASUREMENTS AND RESULTS: Endothelium dependent relaxations to histamine were clearly distinguished from endothelium independent relaxations by their transient nature and their inhibition by pyrilamine, but not by cimetidine. While most distal rings (group I, n = 42/58) and only some of the proximal rings (group II, n = 10/83) showed greater than 50% relaxation with histamine, nearly half the proximal rings (group III, n = 40/83) showed only contraction. Significant differences were found between group I and III, but not II, in control [-66(SD 15.2)% v +25(20.4)%, p less than 0.001] and after pyrilamine treatment [-66(9.2)% v -25(12.0)%, p less than 0.001], cimetidine treatment [-30(25.5)% v +42(20.9)%, p less than 0.001] and endothelial removal [-24(37.1)% v +36(20.2)%, p less than 0.01]. However, a combination of cimetidine and endothelial removal resulted in a contraction to histamine which was similar among the three groups. CONCLUSIONS: These results suggest that hypercontractility to histamine was found in proximal human coronary arteries, but not in distal ones, probably due to the reduction of both direct and endothelial mediated relaxations rather than to an increase in the contraction itself. PMID- 2224928 TI - Non-invasive evaluation of segmental pressure drop and resistance in large arteries in humans based on a Poiseuille model of intra-arterial velocity distribution. AB - STUDY OBJECTIVE: The aim of the study was to evaluate in hypertensive subjects the longitudinal pressure drop and segmental resistance in a large artery in relation to shearing forces of the circulating blood column at the arterial wall. DESIGN: Arterial diameter, blood velocity, and flow were measured in the brachial artery using pulsed Doppler apparatus. Blood viscosity was measured at 96 s-1 with a low shear viscometer. Segmental resistance per unit arterial length was calculated using the basic Poiseuille resistance expression from the ratio between blood viscosity and the fourth power of arterial diameter. Longitudinal pressure drop was deduced as the product between segmental resistance and blood flow. The Poiseuille model of velocity distribution also enabled wall shear rate and stress to be calculated from the ratio between blood velocity and arterial diameter and from the product between shear rate and blood viscosity respectively. PATIENTS: 19 ambulatory male patients with mild to moderate hypertension and 11 normotensive male controls of similar age were studied. RESULTS: Compared to controls, hypertensive patients had higher arterial diameter (p less than 0.001) lower blood velocity (p less than 0.05), higher blood viscosity (p less than 0.01), lower segmental resistance and pressure drop (p less than 0.001, p less than 0.01) and lower shear rate and stress (p less than 0.01, p less than 0.05). A negative correlation existed in the overall normotensive and hypertensive population between pressure drop and mean blood pressure (r = -0.55, p less than 0.01). CONCLUSION: The hypertensive state is associated with a clear reduction in large artery segmental resistance and longitudinal pressure drop concomitantly with a decrease in shear conditions at the arterial wall. The mechanisms of reduced resistance and pressure drop are related to decreased wall shear and increased diameter of the artery, both of which reduce the frictional forces at the blood-arterial wall interface. PMID- 2224929 TI - Cardiac baroreflex function during postural change assessed using non-invasive spontaneous sequence analysis in young men. AB - STUDY OBJECTIVE: The aim was to assess the value of baroreflex sensitivity estimates calculated from analyses of spontaneous systolic blood pressure and pulse interval sequences derived from continuous non-invasive finger blood pressure recordings during sitting and active standing. DESIGN: Continuous recordings of digital systolic blood pressure and pulse interval were obtained non-invasively using a Finapres FD5 during 5 min trials of sitting and standing. SUBJECTS: Subjects were healthy males aged 19-28, divided into those with "high" normal (n = 18) and "low" normal (n = 17) blood pressure. MEASUREMENTS AND MAIN RESULTS: Recordings were scanned for spontaneous sequences of three or more cardiac cycles over which systolic blood pressure increased progressively in conjunction with prolonged pulse interval, or decreased while pulse interval became shorter. Regressions between blood pressure and pulse interval (r greater than 0.80) provided estimates of cardiac baroreceptor reflex control. Computations were carried out with concurrent blood pressure and pulse interval measurements, and with a delay or lag of one and two cycles between the two variables. Pulse interval was reduced from an average 870.3 ms sitting to 571.3 ms on standing. Mean baroreflex sensitivity while sitting averaged 17.5 ms.mm Hg 1 at a delay of one cycle, failing to 7.65 ms.mm Hg-1 with standing. The decrease in sensitivity was correlated with the change in pulse interval between trials. The number of sequences was also significantly reduced with standing as opposed to sitting. Three cycle sequences were most frequent, with a lesser number of sequences involving 4, 5, and 6 or more cycles. No significant differences between "high" and "low" normal blood pressure groups were observed. CONCLUSIONS: The analysis of spontaneous sequences from non-invasive recordings may provide useful information concerning cardiac baroreflex control in different postural and behavioural states. A lag of one cycle between systolic blood pressure and pulse interval may provide the most representative estimates of baroreflex sensitivity. PMID- 2224930 TI - Effect of acute cardiac tamponade on left ventricular pressure-volume relations in anaesthetised dogs. AB - STUDY OBJECTIVE: The aim was to determine whether depressed myocardial contractility is responsible for the decline in stroke volume that occurs with cardiac tamponade. DESIGN: Left ventricular contractile performance was assessed before and after beta adrenergic blockade using the end systolic pressure-volume relation, the left ventricular dP/dtmax-end diastolic volume relation, and the left ventricular stroke work-end diastolic volume relation during acute cardiac tamponade in dogs. EXPERIMENTAL MATERIAL: In eight pentobarbitone anaesthetised dogs (15.7-24.8 kg), transducer tipped and volume impedance catheters were positioned in the left ventricle. Through a median sternotomy incision, a pericardial catheter was inserted to produce varying stages of cardiac tamponade. By the use of transient bicaval occlusions, variably loaded pressure-volume loops were recorded. MEASUREMENTS AND RESULTS: Incremental tamponade reduced mean arterial pressure from 105(SEM 3) to 89(2) mm Hg (mild tamponade), 75(2) mm Hg (moderate tamponade), and 59(10) mm Hg (severe tamponade). The slope of the end systolic pressure-volume relation was 6.3(1.2) mm Hg.ml-1 at baseline and increased slightly to 7.7(1.8), 8.5(1.3), and 9.2(1.5) mm Hg.ml-1 with the progressive levels of tamponade (NS). The role of autonomic reflexes was assessed by repeating the tamponade sequence after beta adrenergic blockade with 10 mg of metoprolol intravenously. The slope of the end systolic pressure-volume relation was reduced by metoprolol, at 4.9(1.0) mm Hg.ml-1 (p less than 0.01), but was not significantly altered by the sequence of tamponade following beta blockade [5.6(0.9), 6.0(1.0), and 5.5(7.0) mm Hg.ml-1, respectively (NS)]. Neither were changes found indicative of depressed contractile function with progressive tamponade in the slopes of the left ventricular dP/dtmax-end diastolic volume and stroke work-end diastolic volume relations. CONCLUSIONS: Left ventricular contractility was not altered during acute cardiac tamponade in an anaesthetised, closed chest canine model. Depressed left ventricular contractile function was not responsible for the observed haemodynamic deterioration. PMID- 2224931 TI - Cardiac muscle function following chronic dietary potassium depletion in the rabbit. AB - STUDY OBJECTIVE: The aim was to investigate a possible defect in cardiac muscle contractile performance following chronic K+ depletion. DESIGN: Cardiac muscle force development, membrane potential, and action potential configuration were measured in isolated superfused right ventricular papillary muscles or trabeculae from control or K+ depleted NZW rabbits. The effects of adrenaline, strophanthidin, and changes in external [Ca2+] and [K+] were investigated. EXPERIMENTAL MATERIALS: Experiments were performed on 50 adult NZW rabbits, average weight 2.3 kg, which were fed either a control diet (n = 25), or a K+ deficient diet (n = 25) for 25 d. MEASUREMENTS AND MAIN RESULTS: There was a significant reduction in contractile force in preparations from the K+ depleted group compared to those from control animals. This was associated with an increased positive inotropic response to low [K+], but an apparent reduction in response to adrenaline. There was no significant difference between groups as to the effect of strophanthidin. CONCLUSIONS: It is suggested that the reduction in response to adrenaline reflects a down regulation in beta receptor density, due to an increased level of circulating catecholamines, and that the defect in myocardial function is a result of adaptive changes to Ca2+ handling mechanisms within the cell. PMID- 2224932 TI - Antiarrhythmic effect of amiodarone on doxorubicin acute toxicity in working rat hearts. AB - STUDY OBJECTIVE: The clinical application of doxorubicin, a potent cytotoxic agent, is limited by a dose dependent cardiotoxicity and by the acquired resistance of the neoplastic cells. Recently, the sensitivity of resistant cancer cells to doxorubicin has been enhanced by the acute administration of amiodarone. The aim of this study was to investigate whether or not this potentiates the cardiotoxicity of doxorubicin. DESIGN: Hearts from rats pretreated or not with amiodarone 50 mg.kg-1.d-1 for 5 d were perfused via the left atrium with a Krebs Henseleit solution containing, or not, doxorubicin 6 mg.litre-1. After 40 min of perfusion, the left main coronary artery was ligated and the ligature was maintained for 10 min. It was then cut and reperfusion continued for 10 min. The cardiac output, heart rate, and mean fibrillation duration induced by the reperfusion were measured by timed collections and ECG recordings. SUBJECTS: 32 adult male Sprague-Dawley rats (250-300 g) were used throughout the study. MEASUREMENTS AND RESULTS: After 40 min of perfusion, the cardiac output in the control and amiodarone groups was constant, but significant decreases of 25.5 and 30.4% were noted in both doxorubicin groups. The mean fibrillation durations observed during reperfusion were 331(73), 66(22), 444(86), and 22(9) s for the control, amiodarone, doxorubicin and amiodarone-doxorubicin groups respectively. CONCLUSION: Amiodarone, while maintaining its antiarrhythmic effect, did not potentiate the negative inotropic effect of doxorubicin. These results suggest that the cardiotoxicity produced by the clinically acute administration of amiodarone with doxorubicin is not greater than that caused by doxorubicin given alone. PMID- 2224933 TI - Effect of activation sequence on ventricular refractoriness as determined by extrastimuli. AB - STUDY OBJECTIVE: The aim was to determine by the extrastimulus method the effect on the right and left ventricular effective refractory periods of moving the site of the pacing train away from the site of the extrastimulus. DESIGN: The ventricular effective refractory period was measured at the right and left ventricular apices using pacing trains at two heart rates, delivered to the ipsilateral ventricle, the contralateral ventricle, and the right atrium. SUBJECTS: Seven patients (six male), mean age 52 years (range 26-75 years), with either documented (six) or suspected (one) ventricular tachycardia were studied. Four had ischaemic heart disease and the remaining three had morphologically normal hearts. MEASUREMENTS AND MAIN RESULTS: The pacing train and extrastimulus delivered in the right ventricle produced the shortest effective refractory period at both heart rates: 220.8(SD 19) ms and 207.9(16) ms respectively. As the pacing train was moved to the right atrium, the effective refractory period lengthened to 246.4(22) ms and 219.3(20) ms at the two heart rates. There was further lengthening as the site of the pacing train was moved to the left ventricle, to 269.2(20) ms and 240.7(35) ms respectively. The same pattern was observed in the left ventricular effective refractory periods as the pacing train was moved from left ventricle to right ventricle and to right atrium. CONCLUSIONS: The ventricular effective refractory period lengthens as the site of the pacing train is moved away from the site of the extrastimulus. This may be explained by the effects of the distribution of the pacing energy within the myocardium and by intercellular electrotonic interactions. This has important clinical implications for the arrhythmogenic mechanisms of ventricular tachyarrhythmias. PMID- 2224934 TI - Loss of blood platelet adhesion after heating native and cultured human subendothelium to 100 degrees Celcius. AB - STUDY OBJECTIVE: Balloon angioplasty produces mechanical vessel wall injury that leads to substantial blood platelet deposition at the angioplasty site. The aim of the study was to determine whether thermal angioplasty might, by contrast, reduce platelet adhesion by denaturation of subendothelial adhesive proteins. DESIGN: Native and cultured human subendothelium was briefly heated to greater than or equal to 100 degrees C by laser irradiation or to 50-100 degrees C by immersion in preheated phosphate buffered saline (PBS). Subsequently, the subendothelium was exposed for 5 min to flowing human blood at a shear rate of 1300 s-1. Blood platelet adhesion to the subendothelium was determined quantitatively. EXPERIMENTAL MATERIAL: Human umbilical arteries were used and the subendothelial matrix derived from cultured umbilical vein endothelial cells. MEASUREMENTS AND RESULTS: After heating arterial subendothelium by laser irradiation to greater than or equal to 100 degrees C, zero platelet adhesion was found v 36(SD 2)% adhesion to the non-heated surface (p less than 0.001). After laser heating of the subendothelial matrix to greater than or equal to 100 degrees C, platelet adhesion was absent in 10/10 experiments (p less than 0.01). After heating the matrix to 100 degrees C by immersion in PBS, platelet adhesion was reduced to 5(5)% v 31(7)% at 37 degrees C (p less than 0.001). CONCLUSIONS: These in vitro results, if extrapolated to catheter interventions, suggest that thermal injury to the vessel wall by laser angioplasty or other thermal angioplasty methods may provide a basic and clinically relevant advantage over mechanical angioplasty modalities, because of a potentially reduced risk of complications related to platelet adhesion. PMID- 2224935 TI - Effects of the free radical generating system FeCl3/ADP on reperfusion arrhythmias of rat hearts and electrical activity of canine Purkinje fibres. AB - STUDY OBJECTIVE: The aim was to evaluate the arrhythmogenic effect of a free radical generating system, FeCl3/ADP using two different approaches. DESIGN: Ventricular arrhythmias were studied in isolated rat hearts subjected to regional ischaemia and reperfusion without or with simultaneous treatment with nicergoline (0.4 mg.litre-1). In the second part of this study the electrophysiological effects of FeCl3/ADP (0.1/1.0 microM) were investigated in normal Purkinje fibres and in Purkinje fibres from dog surviving infarction, by using conventional microelectrode method. EXPERIMENTAL MATERIALS: Hearts were obtained from male Sprague-Dawley rats, weight 250-300 g. Purkinje fibres were dissected from hearts of mongrel dogs of either sex (10-15 kg) with or without prior myocardial infarction. MEASUREMENTS AND RESULTS: FeCl3/ADP (0.1/1.0 microM and 1.0/1.0 microM respectively) weakly changed the incidence of reperfusion induced arrhythmias. In nicergoline pretreated hearts, in which the incidence of reperfusion arrhythmias was reduced, FeCl3/ADP (0.1/1.0 microM and 1.0/1.0 microM) did not change the incidence and the duration of reperfusion arrhythmias. In normal Purkinje fibres, FeCl3/ADP (0.1/1.0 microM) induced a decrease in action potential duration without any pronounced effect on Vmax, diastolic potential, and activation potential. In Purkinje fibres from post infarct myocardium, FeCl3/ADP decreased action potential duration, diastolic potential, and activation potential. CONCLUSIONS: Free radical generation did not antagonise the antiarrhythmic activity of alpha adrenergic blockade. Free radical generation induced slow and minor changes in electrophysiological activity of Purkinje fibres both from normal and ischaemic hearts. Our data suggest that free radical generation may not be the only mechanism involved in the genesis of reperfusion arrhythmias. PMID- 2224936 TI - Photoactivation of porphyrins: studies of reactive oxygen intermediates and arrhythmogenesis in the aerobic rat heart. AB - STUDY OBJECTIVE: In situ production of reactive oxygen intermediates (singlet oxygen and superoxide) during the photoactivation of rose bengal can induce arrhythmias in the aerobically perfused rat heart. The present study was undertaken (1) to assess whether these effects occur with other photosensitizers; (2) to identify the injurious intermediates; (3) to probe the site of action of these phenomena. DESIGN - The study involved the use of meso-tetra-(4 sulphonatophenyl)-porphine (TPPS), a porphyrin which, in contrast to rose bengal, promotes the production of singlet oxygen alone when illuminated. After 10 min of TPPS free perfusion, rat hearts (n = 6 per group) were perfused aerobically with TPPS (1, 5, 10 or 50 mumol.litre-1) for 25 min; during the last 20 min, the hearts were illuminated (3600 lux). In additional studies, TPPS (50 mumol.litre 1) was washed out before illumination. EXPERIMENTAL MATERIAL: Hearts from 30 male Wistar rats, weighing 220-280 g, were excised and perfused retrogradely. MEASUREMENTS AND MAIN RESULTS: Cardiac function was unaffected with TPPS alone. Upon illumination, electrocardiographic changes (increase in QT interval and/or T wave changes) and arrhythmias developed in a dose dependent manner. At the highest dose, electrocardiographic changes occurred within 7.0(SEM 0.4) s; all hearts exhibited ventricular premature beats and complete atrioventricular block; 67% developed ventricular tachycardia and 17% ventricular fibrillation. During illumination, hearts also exhibited a dose and time dependent decrease in coronary flow. In additional studies, despite the absence of TPPS in the perfusate, all hearts exhibited complete atrioventricular block, 67% developed ventricular premature beats and 33% ventricular tachycardia; none exhibited ventricular fibrillation. CONCLUSIONS: The results suggest that singlet oxygen, as opposed to superoxide, is responsible for the injury which occurs at tissue surfaces to which photosensitizer is bound. PMID- 2224937 TI - Nisoldipine inhibits lipid peroxidation induced by coronary occlusion in pig myocardium. AB - STUDY OBJECTIVE: The aim was to investigate the effect of the Ca++ channel blocker nisoldipine on the content of lipid peroxidation products in pig myocardium after acute coronary occlusion. DESIGN: Open chest pigs were subjected to the occlusion of the left anterior coronary artery (LAD) with or without nisoldipine. After 30 min ischaemia, myocardial samples were taken from the ischaemic area and from the non-ischaemic posterior wall of the left ventricle for determination of lipid peroxidation products. SUBJECTS: Subjects were farm pigs of either sex. In 10 pigs, the LAD was occluded without drug pretreatment; 11 pigs were infused with nisoldipine (10 micrograms.kg-1) 30 min before the LAD occlusion. Sham operated controls received no drug (n = 7) or nisoldipine (n = 9). MEASUREMENTS AND MAIN RESULTS: Myocardial samples were assayed for the content of lipid peroxidation products: malondialdehyde, conjugated double bonds, and fluorescent end products. Plasma nisoldipine concentration was measured in some experiments. Following the LAD occlusion, the content of lipid peroxidation products increased in both ischaemic and non-ischaemic myocardial regions as compared to the hearts of sham operated pigs. Pretreatment with nisoldipine completely prevented these increases. At a time of the coronary occlusion, plasma nisoldipine concentrations were within the therapeutic range. CONCLUSION: Ca++ antagonist prevents the excessive peroxidation of myocardial membrane lipids which affects the whole myocardium when there is acute local ischaemia. Prevention of myocardial damage in the non-ischaemic region may determine survival of the infarcted heart. PMID- 2224938 TI - Occlusion time dependency of regional noradrenaline release and cardiac arrhythmias during reperfusion of acutely ischaemic heart in the dog in vivo. AB - STUDY OBJECTIVE: The aim was to study the occlusion time dependency of reperfusion induced increases in regional cardiac noradrenaline release from the ischaemic area in relation to the incidence of ventricular arrhythmias. DESIGN: The left anterior descending coronary artery was ligated for 15, 30 and 60 min in three separate groups of dogs (n = 10 per group). Each occlusion period was followed by a 30 min reperfusion period. The coronary sinus and the epicardial vein running in parallel with the left anterior descending coronary artery were cannulated for measurement of noradrenaline and lactate. EXPERIMENTAL MATERIAL: 30 adult mongrel dogs, 22.5(SEM 1.1) kg, were used for the study. The animals were anaesthetised with sodium pentobarbitone. MEASUREMENTS AND MAIN RESULTS: During occlusion, epicardial venous blood noradrenaline concentrations remained unchanged up to 30 min, but increased from 0.133(0.027) ng.ml-1 to 0.289(0.069) ng.ml-1 after 60 min of occlusion (p less than 0.05). However, epicardial venous blood lactate concentrations increased immediately upon occlusion, and remained elevated (p less than 0.05) during the whole period of occlusion in all groups. Neither noradrenaline nor lactate concentrations in coronary sinus blood increased during occlusion. During reperfusion, nine dogs showed early ventricular fibrillation. The highest incidence of fibrillation (n = 5/10) was found in the 15 min occlusion group, but the difference was not significant between groups. Epicardial venous blood noradrenaline concentrations increased to 0.371(0.076) ng.ml-1, 0.470(0.178) ng.ml-1, and 1.824(0.713) ng.ml-1 upon reperfusion following 15, 30 and 60 min occlusion, respectively (each p less than 0.05). Maximum increases in epicardial venous blood noradrenaline concentrations during reperfusion were correlated with duration of preceding occlusion (r = 0.60, n = 21, p less than 0.01). Maximum increases in mean arrhythmic ratios observed during the first 10 min of reperfusion were proportionally related to mean epicardial venous blood noradrenaline concentrations. The increases in epicardial venous blood noradrenaline concentrations and the incidence of ventricular arrhythmias in the 60 min occlusion group were greater (p less than 0.05) than in the other two groups. CONCLUSIONS: This study shows that noradrenaline is released progressively from the ischaemic area during occlusion for 60 min. The amount of noradrenaline washed out upon reperfusion and the incidence of reperfusion ventricular arrhythmias both appear to be dependent upon duration of preceding occlusion. The results suggest that cardiac noradrenaline released locally from the ischaemic region may contribute to the genesis of reperfusion ventricular arrhythmias, but not to that of reperfusion ventricular fibrillation. PMID- 2224939 TI - Effects of nifedipine on systemic hydraulic vascular load in patients with hypertension. AB - STUDY OBJECTIVE: The aim of the study was (1) to determine the difference in aortic input impedance and derived parameters between hypertensives and normotensives; and (2) to assess the acute effects of nifedipine on the aortic impedance, compliance, and resistance in patients with hypertension. DESIGN: A high fidelity multisensor catheter (Millar) was used to obtain the aortic pressure and flow signals for impedance analysis. The acute effects of nifedipine on the impedance parameters were evaluated at steady state before and after (10 30 min) a sublingual dose of 10 mg. PATIENTS: The patients included seven normotensive (mean blood pressure, 97 mm Hg) and nine hypertensive (mean blood pressure, 135 mm Hg), age matched, ethnic Chinese. Patients with clinical evidence of heart failure and valvular or congenital heart diseases were excluded. MEASUREMENTS AND MAIN RESULTS: Pulsatile aortic flow and pressure were measured by Millar catheter inserted into the ascending aorta. Cross sectional area of aorta was estimated by echocardiograms. Cardiac output was determined by Fick principle with an oximeter. These data were subjected to Fourier analysis for impedance spectra. In comparison with normotensives, hypertensives had increased peripheral vascular resistance R, at 2751(705) v 1651(363) dyne.s.cm-5; increased characteristic impedance Zc, at 193(64) v 122(27) dyne.s.cm-5; and increased first zero crossing frequency of impedance phase angle fo, at 4.8(0.9) v 3.4(0.7) Hz. Arterial compliances corresponding to peak systolic pressure Cs were lower, at 0.32(0.19) v 0.90(0.32) ml.mm Hg-1, as was mean pressure Cm, at 0.55(0.25) v 1.24(0.38) ml.mm Hg-1, and end diastolic pressure Cd, at 0.83(0.29) v 1.65(0.44) ml.mm Hg-1. Although the values of external ventricular hydraulic power were higher in hypertensive subjects, the difference was not statistically significant. Nifedipine administration in 7/9 hypertensives significantly reduced R, from 2806(721) to 2433(664) dyne.s.cm-5; mean aortic pressure Pm, from 138(22) to 112(12) mm Hg; total external ventricular power Wt, from 1452(306) to 1121(135) mW; and steady external power Ws, from 1251(310) to 939(119) mW; but did not reduce Zc, fo, Cs, Cm, Cd, and oscillatory external power Wo. CONCLUSIONS: The results indicate that (1) the stiffness of proximal aorta and vascular tone of peripheral arterioles are higher in hypertensives than in normotensives; (2) in hypertensive subjects, sublingual administration of nifedipine reduces the arterial pressure and peripheral arteriolar tone, but not the stiffness of proximal aorta; (3) the decrease in total external ventricular power in hypertensives treated with nifedipine results from a reduction in the steady, but not the oscillatory, component of hydraulic external ventricular power. PMID- 2224940 TI - Indomethacin suppresses the coronary flow response to hypoxia in exercise trained and sedentary rats. AB - STUDY OBJECTIVE: The aim was to determine if prostaglandin like activity might be involved in changes due to exercise training in the coronary flow responses to hypoxia. DESIGN: The coronary flow response to hypoxia was measured under constant perfusion pressure in isolated perfused hearts from 12 endurance exercise trained rats and 12 control rats. Eight hearts were perfused with a solution containing indomethacin, a cyclo-oxygenase inhibitor, to determine its effect on any training induced changes in the coronary flow response to hypoxic stress. EXPERIMENTAL MATERIAL: 24 male Sprague-Dawley rats, 517 (SD 51) g, were used for this study. The animals were anesthetised and the hearts rapidly excised and perfused with a modified Langendorff perfusion system. MEASUREMENTS AND MAIN RESULTS: Under constant perfusion pressure, the hearts of endurance exercise trained rats had a greater increase in coronary flow during hypoxia relative to normoxia than did hearts of untrained rats, at 13.52(2.15) v 9.56(1.05) ml.min 1.g-1 dry heart weight. Indomethacin treatment abolished this difference and lowered coronary flow: exercise -3.81(3.75) ml.min-1.g-1; control 0.38(2.44) ml.min-1.g-1. CONCLUSIONS: The inhibition by indomethacin of the endurance exercise training induced potentiation of the coronary fluid flow response to hypoxia suggests that prostacyclin or a related compound may be involved in this adaptation to exercise. PMID- 2224941 TI - Capillary permeability of 131I-albumin in the resting human forearm. AB - STUDY OBJECTIVE: The aim was to examine capillary permeability of 131I-albumin in the normal, resting human forearm. DESIGN: A bolus injection of 131I-albumin was injected into the brachial artery, and the residue function was measured by external registration over the forearm tissues. The results were analysed by indicator kinetic "black box" theory using the single injection, residue detection method which is based on indicator diffusion principles. SUBJECTS: Seven normal volunteers participated in the study. MEASUREMENTS AND MAIN RESULTS: The mean capillary extraction fraction of 131I-albumin was 0.023 (SD 0.0056), n = 7, at a mean plasma flow rate of 2.1 (0.34) ml.100 g-1.min-1. At an estimated capillary surface area of 70 cm.g-1 the permeability coefficient was 11.10(-8) cm.s-1. CONCLUSIONS: According to the theories of restricted diffusion and equivalent pores the results are compatible with an equivalent pore radius estimate of 113 A using additional previously published results from experiments with 51Cr-EDTA. PMID- 2224942 TI - Influence of electrogenic Na/Ca exchange on the action potential in human heart muscle. AB - STUDY OBJECTIVE: The plateau of the action potential in heart muscle is largely due to the inward Ca2+ current, ica; however, Ca2+ extrusion via Na+/Ca2+ exchange may also generate a significant current, ina/ca. The aim was to assess the influence of ina/ca on the action potential in isolated human heart muscle. DESIGN: Action potentials and force of isometric contractions were recorded in ventricular trabeculae. The muscle was subjected to various stimulus patterns, Ca2+ antagonists, and variations in the ionic composition of the extracellular medium. PATIENTS: From 49 patients, aged 0.5 to 14 years, small right ventricular trabeculae were obtained during open heart surgery. The operations concerned corrections of ventricular septal defects. Data presented in this paper were from nine preparations in which action potentials were recorded during several hours. MEASUREMENTS AND MAIN RESULTS: The results confirmed that: (1) the amplitude of the early part of the plateau was depressed by low [Ca2+] and by Ca2+ antagonists, showing that ica dominates this early part; and (2) that low [Na2+] and post-extrasystolic potentiation also depressed the early component of the plateau of the action potential, which can be explained by inactivation of ica due to increased levels of intracellular Ca2+. A novel observation was that post extrasystolic potentiation led to an increase in action potential duration (APD). An explanation is that the potentiated contraction follows from an increased amount of intracellular Ca2+ which also activates an inward current, possibly ina/ca. This assumption is strengthened by the finding that lengthening of APD after extrasystoles was abolished: (a) at low [Ca2+], ie, when force was small and there was little Ca2+ to be extruded; and (b) at low [Na+], ie, when force was large but the driving force of the Na+ gradient for extrusion of Ca2+ was small. CONCLUSIONS: The early part of the plateau is dominated by ica, whereas ina/ca is relatively more important during the later part, and tends to lengthen the action potential. PMID- 2224944 TI - Dexamethasone and nonsteroidal anti-inflammatory agents in the treatment of bacterial meningitis. AB - It has been shown in experimental models of bacterial meningitis that bacterial cell-wall components produce an inflammatory response in the subarachnoid space, probably by stimulating the release of inflammatory cytokines, such as tumor necrosis factor, interleukin-1, and prostaglandins. Interleukin-1 increases the concentration of prostaglandin E2 and leukotriene B4, metabolites of arachidonic acid, which are potent mediators of inflammation. Steroidal and nonsteroidal anti inflammatory agents decrease formation of these metabolites and minimize the damage to the blood-brain barrier. There is also evidence that anti-inflammatory agents decrease cerebral edema in bacterial meningitis. The results of clinical trials in patients with bacterial meningitis demonstrate that dexamethasone can prevent sensorineural hearing loss and reduce mortality, without interfering with the antimicrobial action of antibiotics. PMID- 2224943 TI - Effects of increased pericardial pressure on the coupling between the ventricles. AB - STUDY OBJECTIVE: The mechanical coupling between the ventricles occurs directly through the myocardium (ventricular-ventricular coupling) and indirectly through the pericardium (ventricular-pericardial-ventricular coupling). We postulated that the magnitude of ventricular-pericardial-ventricular coupling would increase at high pericardial pressures, while ventricular-ventricular coupling would be unaltered. DESIGN: Canine hearts were removed and placed in cold cardioplegic solution. Balloons were inserted into each ventricle and the left and right ventricular pressure (dP1, dPr) and volume (dV1, dVr) changes caused by increasing the pressure and volume of the other ventricle and by increasing pericardial pressure (dPp) were measured. EXPERIMENTAL MATERIALS: Hearts from 10 random source dogs, weight 12.5-18 kg, were used. MEASUREMENT AND MAIN RESULTS: At control pericardial pressure levels, the magnitude of the pericardial ventricular interactions was greater than the ventricular-ventricular interactions: dP1/dPp was significantly greater than dP1/dPr, at 0.71 (SEM 0.04), n = 6, v 0.18 (0.03), p less than 0.01, and dV1/dPp was significantly greater than dV1/dPr, at -0.83 (0.09) v -0.24 (0.06), p less than 0.05. Raising the pericardial pressure increased the mechanical coupling between the ventricles: dP1/dPr approximately, dV1/dPr approximately, dPr/dP1 approximately, and dVr/dP1 approximately increased significantly (p less than 0.05) by 0.48 (0.03), 0.67 (0.13), 0.38 (0.05), and 0.61 (0.09) respectively. This increased coupling occurred through pericardial pressure changes. If pericardial pressure was maintained constant, the coupling between the ventricles was unaltered. This same pattern was observed in four in situ experiments. For these experiments, at the raised pericardial pressure levels, dP1/dPr increased, from 0.51 (0.03) to 0.79 (0.01), p less than 0.05, if pericardial pressure was allowed to vary, but was unaltered with a constant pericardial pressure, at 0.42 (0.03) v 0.44 (0.04), p greater than 0.5. CONCLUSIONS: Ventricular interdependence was increased with raised pericardial pressure and this increased coupling was due primarily to an increased ventricular-pericardial-ventricular coupling. This increased coupling may help to explain the paradoxical pulse observed in cardiac tamponade. PMID- 2224945 TI - Choosing a target for cognitive enhancers. AB - The development of drugs to improve cognitive functions (cognitive enhancers) has been hampered by the failure to define pharmacologic targets. The justifications for the development of cognitive enhancers for medicine, the pharmaceutical industry, and society are outlined. The procedures required for the development of these drugs and their therapeutic objectives are discussed. It is concluded that a better definition of the direct targets of cognitive enhancers can guarantee cost and time savings for the industry and produce a therapeutically effective agent. PMID- 2224946 TI - Inhibitory effects of ulinastatin on the production of cytokines: implications for the prevention of septicemic shock. AB - The study was designed to determine whether ulinastatin can be used as a biological response modifier for the prevention of septicemic shock. Monocytes from heparinized blood of three healthy volunteers were incubated with 0.125 or 1.25 U/ml of ulinastatin, and then endotoxin (Escherichia coli lipopolysaccharide) was added at concentrations of 0.1, 1.0, and 10.0 micrograms/ml. A dose-dependent increase in the production of tumor necrosis factor alpha, interleukin-1 alpha, and interleukin-1 beta was noted after endotoxin stimulation. Production of these cytokines was inhibited by the addition of ulinastatin in a dose-dependent manner. The results indicate that ulinastatin could be useful in the prevention of septicemic shock. PMID- 2224947 TI - Effects of a new calcium channel blocker, TA 3090, on serum lipoprotein levels in mild to moderate essential hypertension. AB - The 25 hypertensive patients received 20 to 40 mg of TA 3090 daily for 12 weeks. Blood pressures declined significantly during treatment, from a mean of 162/98 to 145/88 mmHg. There were no significant changes in levels of total or very low density lipoprotein cholesterol or triglyceride, in levels of low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, or in levels of apolipoprotein (apo) B, C-II, C III, or E. Apo A-I and A-II levels increased significantly from 130 and 29.2 mg/dl before treatment to 152 and 31.4 mg/dl at 12 weeks. Mean serum creatinine levels decreased significantly from 0.92 to 0.80 mg/dl. No other drug-related changes in laboratory test results or side effects were noted. It is concluded that TA 3090 is a safe and effective treatment for mild to moderate hypertension. PMID- 2224948 TI - Nicardipine in the prevention of cerebral infarction. AB - Two hundred and sixty-four patients were included in an open, randomized, multicenter trial, with the aim of determining whether nicardipine can be useful in the prevention of cerebral infarction. The patients had experienced one or more transient ischemic attacks, reversible ischemic neurologic defect, or stroke with minor permanent neurological deficit in the 12 months before enrolling in the study. Each patient was randomly assigned to received 250 mg of aspirin once daily plus 20 mg of nicardipine thrice daily (n = 170) or 250 mg of aspirin once daily (n = 94) for 12 months. During the 12-month treatment period, 12% of the aspirin-plus-nicardipine group and 19% of the aspirin-only group experienced an ischemic cerebrovascular event; at six months, the cumulative incidence of events was significantly lower in the aspirin-plus-nicardipine group than in the aspirin only group. One patient in each group died of a recurrent stroke. Aspirin-related side effects were dyspepsia (reported by four patients), heartburn (by seven), nausea and vomiting (by four), and melena (by five); nicardipine-related side effects were transient hypotension (by two), headache (by four), ankle edema (by three), and constipation (by four). Results indicate that the addition of nicardipine to antiplatelet treatment may safely prevent the recurrence of ischemic cerebrovascular events. PMID- 2224949 TI - Evaluation of IPM/CS in gram-negative bacillus infections: use of an endotoxin specific assay. AB - The subjects were 26 patients hospitalized with severe trauma or burns. Twice daily for seven to 14 days, 1 gm of IPM/CS (a 1:1 combination of imipenem and cilastatin sodium) was administered by intravenous drip infusion to each patient. Clinical outcome was rated excellent in nine patients, good in 12, and fair in five. Bacteria, isolated in 21 of the 26 patients, were eliminated in 18 and decreased in three. Mean endotoxin levels, assessed by the Endospecy method, were reduced from 167.8 pg/ml before treatment to 5.1 pg/ml after treatment. No treatment side effects were noted. PMID- 2224950 TI - Desmopressin acetate in children with severe primary nocturnal enuresis. AB - Desmopressin acetate, a synthetic antidiuretic drug, was evaluated in two US multicenter studies involving a total of 176 children with severe primary nocturnal enuresis. Patients who qualified during the screening period, entered a double-blind treatment phase during which they received 20 micrograms or 40 micrograms of desmopressin acetate or placebo at bedtime for four weeks. This phase was followed by a four-week open-label period, during which all patients received 20 or 40 micrograms of desmopressin acetate. In both studies, children given desmopressin acetate had significantly fewer wet nights after two and four weeks of therapy than did children given placebo. During the open-label period, patients crossed over from placebo to desmopressin acetate showed similar reductions in enuresis. Global evaluations by the patients, their parents, or the investigators further confirmed the good results with desmopressin acetate. No serious adverse experiences were reported. Thus the results of these studies corroborate previously published reports of the efficacy and safety of desmopressin acetate in the treatment of primary nocturnal enuresis. PMID- 2224951 TI - Milestones in clinical pharmacology. Tuberculosis. PMID- 2224952 TI - A quantitative histochemical study of the microvasculature of irradiated skin. AB - Short-term X-ray damage to the microvasculature of the skin of newborn rats has been quantitated using Horseradish Peroxidase as a tracer. Image analysis of thick sections on which peroxidase was demonstrated histochemically revealed a radioinduced increase in vascular volume coupled with a decrease in vascular length and an altered frequency distribution of blood vessel calibers which resulted in early telangiectasia. The results afforded by direct counting of peroxidase positive macrophagic cells and microphotometric evaluation of peroxidase present in the connective tissue indicate a progressive increase in capillary permeability as a function of dose and time post-irradiation. The accuracy with which the affected region of blood vessels coincided with the area exposed to the beam favours the hypothesis of direct damage to the vessel wall as a major cause of radioinduced lesion. PMID- 2224953 TI - Phosphorylation of ornithine decarboxylase by casein kinase II from RAW264 cells. AB - Casein kinase II and ornithine decarboxylase were purified from a virally transformed macrophage-like cell line, RAW264. The addition of casein kinase II to a reaction mixture containing [tau-32P]GTP, Mg++, and ornithine decarboxylase led to the phosphorylation of a 55,000 dalton protein band in the purified preparation of ornithine decarboxylase. Stoichiometric estimates indicated that casein kinase II incorporated 0.15 mole of phosphate per mole of ornithine decarboxylase, which was increased to 0.3 mole/per mole in the presence of spermine. The apparent Km and Vmax values for the casein kinase II-mediated phosphorylation of ornithine decarboxylase were 0.36 microM and 62.5 nmol/min./mg kinase. The addition of spermine to the reaction did not alter the Km but increased the Vmax to 100 nmol/min./mg kinase. The phosphorylation of ornithine decarboxylase by casein kinase II affected neither the rate of maximal ornithine decarboxylase activity nor the affinity of the enzyme for ornithine. PMID- 2224954 TI - Effect of a luteinizing-hormone-releasing-hormone (LHRH)-analogue on the histochemistry of the secondary alcohol-dehydrogenase in the Leydig cells of the cat testis. AB - The histochemical activities of the enzymes alcohol dehydrogenase with propanol (A-D I) and isopropanol (A-D II) as substrates, 3- beta-hydroxysteroid dehydrogenase (3 beta .OHST-D), nicotinamideadenine dinucleotide phosphate (reduced form)-tetrazolium reductase (NADPH2-TR) and glucose-6-phosphate dehydrogenase (G6P-D) were studied in the testis of 6 cats daily injected with 20 micrograms/kg of the LHRH-analogue DTRP6-DGLY-10, LHRH-ethylamide (LHRH-A Group) and 3 cats injected with saline during 67 days. A morphometric analysis was done to evaluate the activity of the enzymes, its distribution and volume fractions of the Leydig cells with every activity. A-D II displayed a significant inhibition in the Leydig cells of the LHRH-A Group. There were no changes in the activities of G6P-D, 3 beta .OHST-D and NADPH2-TR, but it was possible to disclose some reduction of the volume fraction of the Leydig cells when the first two enzymes were used as its marker. This study corroborates that A-D II is a reaction in the pathway of steroidogenesis but does not explain whether it corresponds actually to 20-22 desmolase as proposed in the work by Hardonk (1965) or to another reaction linked to the activities of the cytochromes P450. PMID- 2224955 TI - Effects of human recombinant IL-1 beta on rheumatoid and non rheumatoid human synovial cell growth. AB - The growth of adherent synovial cells passaged once was studied in response to human recombinant interleukin 1 (hr IL-1) beta. Human synovial cell cultures were established from tissues obtained during therapeutic joint surgery for patients with rheumatoid arthritis (rheumatoid synovial cells, RSC) or non inflammatory rheumatic diseases (non rheumatoid synovial cells, NRSC). The effect of IL-1 beta (0.1 to 10 ng/ml) on the time course of proliferation showed that values for DNA synthesis and cell numbers in RSC cultures were higher than in NRSC cultures. Similarly, untreated control RSC cultures grew more quickly than NRSC. These results demonstrate that RSC, which are continuously stimulated by IL-1 beta produced in the rheumatoid pannus in vivo, have a higher capacity for proliferation than NRSC but are less responsive to IL-1 beta. A dose-response curve of proliferation was established 72 hrs. after the addition of IL-1 to the medium. The stimulating effect of IL-1 beta (0.001 to 10 ng/ml) was dose dependent in both RSC and NRSC and reached a plateau at 10 ng/ml; the response of NRSC was stronger than that of RCS. PMID- 2224956 TI - Effects of lectins on cytoskeleton and morphology or cultured chick embryo fibroblasts. AB - The microfilaments and microtubules of cultured chick embryo skin fibroblasts were studied in the presence of exogenous lectins by an indirect immunofluorescence technique. Lectin treatment induced modifications in the arrangement of myosin, actin and tubulin, determined depolymerization of the proteins and caused changes in cell shape and size. The results suggest that the interaction between lectins and their specific membrane receptors triggers a series of changes in the cytoskeletal pattern via transmembrana as yet unknown mechanisms and that these are responsible for the alterations in cell shape and size. PMID- 2224957 TI - Messenger-dependent action of guanylylimidodiphosphate and translation inhibitors on rat brain polypeptide synthesis. AB - The effects of the Guanosine 5'-triphosphate analog guanylylimidodiphosphate and several antibiotics on protein synthesis in a cell-free system from rat brain were investigated as a function of the template used. Polypeptide chain elongation was promoted by the analog only in the system coded by the endogenous template but not when coded by polyuridylic acid. The effects of the antibiotics were also dependent on the template used. This suggest that the template conditioned the ribosomal conformation which determine the inhibitory effect of the antibiotics. PMID- 2224958 TI - Influence of the structure of alkanols on their inhibition of protein synthesis in Saccharomyces cerevisiae var. ellipsoideus. AB - The effects of several short chain alcohols on protein synthesis by intact Saccharomyces cerevisiae var. ellipsoideus cells were studied. The results show that the relative inhibitory potencies correlate well with the size of the carbon backbone, thus suggesting that a hydrophobicity-related effect is involved in the inhibitory action of these alcohols. Additionally, the branching nature of the carbon backbone contributes to determining the action of the alcohol, as proved by the relative potencies of the four-carbon alcohol series. PMID- 2224960 TI - [Academician Vilem Laufberger and the Czechoslovak Academy of Sciences]. AB - Academician Vilem Laufberger participated in a significant way in the work of the Czechoslovak Academy of Sciences. He was one of its founders as a member of the preparatory commission for its establishment, an important official in its presidium, founder and director of one of its institutes and a permanent long term critical observer and commentator of its activities. He greatly appreciated the steep rise of biomedical research at the beginnings of the Academy as a worthy development of the traditions of world reknown physiologists J. E. Purkyne and I. P. Pavlov. He evaluated favourably also its subsequent development. At the very beginning he drew attention to some shortcomings which during subsequent development influenced the activities of the Academy in an adverse way. Their elimination is a task for the present time. PMID- 2224959 TI - Coupling of Na+ with the spermidine transporter protein in NIH BALB/c 3T3 cells. AB - This study demonstrates that polyamine spermidine (Spd) transporter protein is directly coupled with the Na+ in a ternary complex form, Na(+)-Spd-carrier. The Spd is transported with Na+ in a 1:1 stoichiometry relationship. Interestingly, addition of 2-deoxyglucose in the assay medium did not influence significantly the Spd uptake demonstrating the ATP independency of Spd transport. PMID- 2224961 TI - [Metamorphosis today]. AB - In conjunction with the 100th anniversary of birth of the Czech physiologist V. Laufberger who discovered in 1913 the possibility to induce metamorphosis in neotenous larvae of axolotls by feeding them with thyroid gland, the author gives an account on the development of knowledge regarding metamorphosis in amphibia. He analyzes the participation of endocrine glands, in particular thyroid hormones and prolactin. Special attention is devoted to mechanisms leading to resorption of the tail in tadpoles, i. e. the activation of lysosomal enzymes due to the action of thyroid hormones. Prolactin has an inhibitory effect on metamorphosis. An important part is obviously played by deiodination of the prohormone thyroxine in target tissues to active triiodothyronine. Recently it was demonstrated that during metamorphosis a significant role is played by apoptosis (controlled non inflammatory absorption of superfluous cells). PMID- 2224962 TI - [Laufberger's excitation theory]. AB - The author gives an account of V. Laufberger's Excitation theory at the occasion of the 100th anniversary of his birthday. This work was published as a monograph in 1947 and contains many data which foresee the further development of neuro sciences and other scientific disciplines. From a certain aspect it is more cybernetic than Wiener's "Cybernetics" published one year later. It applies in a genial way the principle of logical elements made up of binary functional elements, backfeeds, parallel organization of neuron networks, and memories based on so-called spinning excitations. It is the first modern model of cerebral activity. It combines within one system the neuron and psychic level of organization of the brain. PMID- 2224963 TI - [The electrocardiologic period of scientific work of academician Vilem Laufberger]. AB - Laufberger contributed in a fundamental way to the solution of practically all basic problems of the electric field theory of the heart (EPS). He defined the centre of EPS and elaborated the procedure of its determination by means of mirror image ECG and derived the mathematical relationship by means of which it is possible to assess the distance of the surface electrode from the given point inside the chest (1952, 1953) and to correct thus the magnitude of the ECG. On these findings he based his individually corrected vector cardiographic system of leads. By the term cardiale (1961, 1963)--the spatial curve of tension maxima which develop in the EPS during the electric systole of the heart--Laufberger resolved the problem of the physical basis of electrocardiography. Its correlate is the spatioelectrocardiogram (1953)--a spatial curve which developed by "synthesis" of orthogonal ECG of the vector cardiographic system of axes. In orbital spatiocardiography (1961, 1963) he expressed synthetically the topography of shapes of the set of surface ECG, the amplitudes of which correspond to the global area, equidistant in relation to the centre of EPS (orbit). He foresaw by many years the inverse problem solution (i.e., assessment of properties of the EPS source from properties of the body surface potential distribution) by orthogonal transformations, in particular in the shape of the multipole theory. Laufberger generalized the mentioned findings in a mathematical model of EPS (1970-1980) which made it possible to study all laws he revealed and their mutual action on the formation of the set of surface ECG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224964 TI - [The development of theories on the mechanisms of insulin action]. AB - In 1924 Laufberger formulated his block theory on the action of insulin. Its basic thesis that insulin prevents the new formation of glucose and its supply into the blood stream is still valid, although knowledge on the multiple action of insulin expanded substantially. The theory put forward in 1955 by Levine and Goldstein which ascribed all insulin actions to the influence on the cellular membrane permeability for glucose, could, however, not explain all data associated with insulin, the knowledge of which was expanded steadily. At present the mechanism of insulin action is explained most comprehensively by the concept based on the bond of insulin to its membrane receptor which by activation of tyrosine kinase it contains induces either cascade phosphorylation of intracellular protein kinases or (and) leads to the release of the "second messenger" from the cell membrane, i.e. of glycosyl-phosphatidyl inositol. In both instances activation of the glucose and amino acids transmitter from the medium into the cells results, as well as activation of enzymes catalyzing in the cell various degrees of carbohydrate, fat and protein metabolism. PMID- 2224965 TI - [Survival and differentiation of pyramidal cells of the hippocampus after transplantation]. AB - Pyramidal neurons of the CA3 hippocampal area were eliminated by means of the kainic acid. Subsequent transplantation of the embryonal hippocampal tissue suspension brought about an increase of the number of neurons. Groups of nerve cells were located at the tips of the implantation tracts. Neurons formed dendritic trees of various complexity. Most of them had an irregular dendritic branching pattern. Only those located within the pyramidal layer, had the typical arrangement of several basal and one apical dendrite. PMID- 2224966 TI - [Vilem Laufberger--scientist, teacher and physician]. PMID- 2224967 TI - [Health care and the church]. AB - The article is devoted to some basic problems of the relationship of the health services and Church which may appear under the present new circumstances. After a long period of repression of the church to the periphery of society it is necessary to attempt to answer with new courage and mutual confidence what the health services may expect and demand from the church and what the church may expect and what the health services can offer the church. The author deals in more detail with several areas where collaboration between churches and health services seems promising: psychiatry and clinical psychology, nursing, thanatology, prevention. The author mentions the necessity of mutual meeting and enrichment in theoretical areas. PMID- 2224968 TI - [Immunocomplex vasculitis]. AB - The clinician suspects immunocomplex vasculitis when he cannot find a common denominator for the concurrent affection of various neighbouring organs and tissues. These affections result from the inflammatory response of the organism to the deposition of non-phagocytized circulating immunocomplex into the vascular wall. Despite the delicacy of attempts to classify them, the author tried to differentiate them into non-progressing immunocomplexes vasculitis, which recedes, and progressing immunocomplex vasculitis which may be either primary or secondary. Among primary ones he includes nodose polyarteritis and its granulomatous variant, Churg-Strauss' disease, Henoch-Schonlein anaphylactoid purpura and granulomatous vasculitis of the Wegener granulomatosis type, Horton's temporal arteritis, Takayasu's pulseless disease and Winiwarter-Buerger's obliterating thromboangiitis, which may be of the peripheral or more rarely the visceral type. Secondary progressing vasculitis is encountered in so-called "collagenoses" (e.g. systemic lupus erythematodes), where the clinical picture is to a considerable extent conditioned by vasculitis. The clinical picture is due to the generalized affection of the microcirculation. Symptoms of ischaemic affection of all organs and tissues may be encountered. A typical feature are different types of damage of the same adjoining system, e.g. a combination of asymmetric central and peripheral pareses in affections of the nervous system. The author discusses the most frequent clinical pictures, the importance of different examination procedures and therapeutic possibilities. Assessment of the diagnosis of immunocomplex or autoaggressive systemic disease is very difficult, as a typical picture corresponding clearly to a defined nosological unit is encountered rarely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2224969 TI - [Analgesia in extracorporeal shock wave lithotripsy. Experience with a lithotripsy apparatus made in Czechoslovakia]. AB - The authors describe their experience with the use of analgesia during lithotripsy by an extracorporeal impulse wave (LERV). They made a total of 253 lithotripsies in various indications in a total of 150 patients. Most frequently ataracoanalgesia was administered (a combination of diazepam and phentanyl), however, administration of midazolam (Dormicum) is also adequate. This is due among others to the favourable physical properties of the impulse waves generated by the apparatus used. In the discussion the authors give a brief account of the causes of painfulness of LERV, based on contemporary ideas and experience. PMID- 2224970 TI - [Contribution of automatic sphygmomanometers for one-time measurement of blood pressure]. AB - Due to high intra-individual variability of arterial blood pressure, single measurements provide only estimates of true actual values. Two or three recordings made in sequence in one or a few minutes' intervals are recommended in some clinical studies of antihypertensive therapy, with the aim of decreasing the variability. In order to examine the value of repeated measurements made on one occasion, four sequential resting recordings of blood pressure and heart rate made in one minute intervals with the automatic oscillometric Nippon Colin BP 103N sphygmomanometer were evaluated in 66 subjects, using the analysis of variance methods. Means of three recordings showed a significantly lower variability than single measurements (almost by one half), while the difference between three and four readings was not significant. The Page's rank test revealed that the first measurements are not uniformly the highest ones, and therefore the medians of three readings made in sequence are recommended as characteristics of resting blood pressure. An advantage of the oscillometric method is the possibility of measuring mean arterial pressure. The recorded values were significantly higher than those calculated from the systolic and diastolic pressures according to the current formula, being situated between one third and one half of the pulse pressure. The intra-individual coefficient of variation of the recorded mean arterial pressure was comparable with that of systolic and significantly lower than that of diastolic pressure. PMID- 2224972 TI - [Confession, reflection and profession]. PMID- 2224971 TI - [Larval stages of the filaria Mansonella (Dipetalonema) perstans in a student from Africa]. AB - Microfilariae were found in blood samples of a 32 year-old-student from Guinea Bissau (Africa). Based on parasite morphology as well as some other features the microfilariae were identified as Mansonella perstans. The course of infection was asymptomatic (except for slight urticarial skin lesions). The microfilariae disappeared from peripheral blood after mebendazole treatment (200 mg daily for 1 month). PMID- 2224973 TI - [Salutogenesis and behavioral medicine]. AB - As the opposite number of the classical biomedical model the author presents the bio-psycho-social model which attempts to supplement relatively omitted subjects of health and disease. Against the emphasis on pathogenesis he puts salutogenesis -problems leading to "firm health", a good health status despite unfavourable and risk factors, and health promotion. Behavioural medicine associates with this concept the problem of social influences on the development of diseases and their prevention and treatment. At the same time he pays attention to lifestyle, living pattern, habits, attitudes, behaviour and action which influence the health status. The author gives an account of theoretical concepts, subjects and emphasizes aspects of this approach. PMID- 2224974 TI - [Lyme borreliosis in the West Bohemian Region. 2 years' experience]. AB - During the period between 1988-1989 529 cases of Lyme borreliosis were reported to the hygiene service of the West Bohemian region. Of these 164 (31.0%) were confirmed by indirect immunofluorescence. 342 (64.6%) patients reported contact with a tick, another 108 patients reported contact with other arthropods. Among the affected systems the skin and nervous system predominated. From the total number of 443 cases of erythema chronicum migrans the aetiology was confirmed serologically in 84 (19.0%). Comparison of skin diseases confirmed and not confirmed by laboratory tests, classified by age, sex, monthly incidence and contact with arthropods revealed that the clinical diagnosis of skin symptoms of Lyme borreliosis in the West Bohemian region is of a high standard. PMID- 2224975 TI - [An epidemic of type B influenza in the geriatric psychiatry department of a psychiatric hospital]. AB - The authors submit an epidemiological and aetiological analysis of a local epidemic of influenza type B which occurred in April 1989 in a mental hospital at the geronto-psychiatric department. In the course of two weeks 26 patients and 5 health workers from a total of 72 exposed subjects contracted influenza. 50% of the patients who contracted influenza died. The authors emphasize the necessity of early preventive epidemiological provisions in institutions of this type. PMID- 2224976 TI - [External lumbar cerebrospinal fluid drainage with controlled flow-- its use in pediatric neurosurgery]. AB - The authors describe cases of external lumbar CSF drainage with a regulated flow inserted lumbally or in the pseudomeningocele in children. During flow regulation during operation they were guided by the finding in the surgical field, during therapeutic use (in the course of 1-8 days) by setting the CSF output at 15 ml/hour. Drainage was used in extradural approach to the orbit, for treatment of liquorrhoea in surgical wounds of the posterior fossa, frontal and temporal drainage to clear the CSF in meningitis and to make inner drainage possible. CSF fistulae healed even after major craniectomies and infections due to the resistance of allogenic and xenogenic dural transplants. For external CSF drainage the authors used lumbar needles, intravenous Portex kits or original Cordis kits. The latter proved to be the best. PMID- 2224977 TI - [Serum levels and urinary excretion of amino acids during high intensity physical exertion in healthy men]. AB - The authors investigated the effect of a physical load on a bicycle ergometer on serum concentrations and urinary excretion of 19 amino acids. The initial load of 1 W/kg was increased after 5-minute intervals by 10-20 W to achieve the maximum after 50 minutes exercise. During the last 2-3 minutes of the maximal load a spiroergometric examination was made. The serum alanine concentration increased under these conditions significantly from 474 +/- 133 to 739 +/- 171 mumol/l (p less than 0.001), while the serum threonine concentration declined significantly from 155 +/- 39 to 143 +/- 37 mumol/l (p less than 0.05). Urinary excretion and renal clearance of amino acids declined significantly (p less than 0.05-0.001). The authors found a significant correlation between the drop of the urinary excretion and the rise of serum concentration of alanine (p less than 0.05). The drop of the urinary alanine excretion can contribute to its elevated serum concentration. The fractional amino acid excretions did not decline and the decline of amino acid and creatinine clearances was more or less proportional. The authors conclude that the decline of amino acid excretion is directly associated with a drop of glomerular filtration. The revealed, correlations between the drop of gin, lys, pala, thr and Na excretion suggest that the sodium transport through the nephron can influence the transport of these amino acids. PMID- 2224978 TI - [UNICEF report for 1990]. PMID- 2224979 TI - [Chelating agents]. AB - The problem of chelating agents used as antidotes in intoxications with metals is intensively studied during the past 20 years. Due to the complex nature of the action of these substances in the organism their investigation is a typically interdisciplinary problem. The submitted review gives the theoretical background of the formation of chelate in the organism, the strategy of research of new substances is discussed and findings on the main groups of chelating agents used in human medicine are summarized. PMID- 2224980 TI - [Relation of diabetic polyneuropathy to vascular and organ complications in type I diabetes mellitus]. AB - The authors investigated in 194 type I diabetics the incidence and severity of diabetic polyneuropathy in relation to other organ and vascular complications, incl. autonomous neuropathy. It was revealed that the increasing severity of polyneuropathy was significantly v seru (Cr equal to or less than 130-200 mumol/l); 4--Cr greater than 200 mumol/l; associated with severe stages of nephropathy and proliferative retinopathy with amaurosis. The concurrent presence of hypertension and polyneuropathy was surprising and striking--even in patients with the mildest grade 1 polyneuropathy hypertension was present in 10% and the incidence increased significantly with the increasing severity of polyneuropathy. Ischaemic heart disease and ischaemia of the lower extremities was significantly more frequent only in patients with grade 5 polyneuropathy. In patients with grade 4 and 5 neuropathy there was a 100% incidence of autonomous neuropathy in the cardiovascular sphere. The authors did not reveal significant differences between men and women as regards the relationship between the incidence of polyneuropathy and organ and vascular complications. PMID- 2224981 TI - [Therapeutic effectiveness of thrombocyte concentrates in relation to the results of the lymphocytotoxicity test]. AB - The authors analyze the effect of transfusions of 211 thrombocyte concentrates to polytransfused patients in relation to the results of the crossover test between donor and recipient, using the lymphocytotoxic test (LCT). In negative LCT tests the adequate and inadequate effect was 50%. After elimination of non-immune influences (splenomegaly, febrile temperature) the percentage of adequate effects rose to 70%. In LCT positive results the effect of administration of thrombocyte concentrates declined to 30%. The authors discuss practical possibilities and ways to select suitable donors to achieve an optimal therapeutic effect of substitution therapy. PMID- 2224982 TI - [The President-Liberator in the memories of his physician]. PMID- 2224983 TI - [Thomas Garrigue Masaryk and Eduard Albert]. PMID- 2224984 TI - [Sleep in old age and its disorders]. AB - Ageing is associated with deterioration of the quality of nocturnal sleep, more frequent siestas in the afternoon, a forward shift of sleep in the 24-hour cycle. In old age sleep disorders are more frequent such as sleep apnoea, the restless feet syndrome, periodic movements of the lower extremities and others. The authors present an account of changes of sleep and vigilance and the most frequent sleep disorders in old age. PMID- 2224985 TI - [The practicum in physiology: from Laufberger to today]. AB - An outline of Prof. Laufberger's concept of practical exercises in physiology, proposed just after the Second World War, is given. Especially, his new pedagogical approach is emphasized, here. Further, the development of the organization of practical courses in the Institute of Physiology in Prague is described: e.g. the modernization of the methods used, and of the educational process in early 70 s'. Today, the importance of biocybernetics is growing. PMID- 2224986 TI - [Comparative histomorphometric study of acromegalic spongy bone. Formative static parameters]. AB - The authors used static histomorphometric parameters obtained by processing of bioptic bone specimens for comparison of normal and acromegalic spongious bone. Parameters of the bone volume (V), osteoid volume (Vos), the extent of osteoid bone surfaces (Sf) in the two groups do not differ statistically. The two groups do not differ as to age distribution. The width of bone trabeculae is greater in acromegalic bone; the difference as compared with normal bone specimens is statistically significant (p less than 0.05). The authors conclude that STH in acromegalics subjects does not stimulate osteoid production in trabecular bone to shift the balance between bone resorption and formation significantly in favour of formation. Only restructuring of trabecular acromegalic bone occurs. PMID- 2224987 TI - [Possibilities of measurement of obstruction in status asthmaticus]. AB - Basic treatment of status asthmaticus comprises among others the use of artificial pulmonary ventilation with all advantages and risks. The authors tried to express objectively the extent of obstruction of the airways from the relationship of ventilation parameters obtained from a display unit of Siemens Elema 900C ventilator and the period of intubation. Based on the investigated parameters, the inspiration pressure, the median intrathoracic pressure and pulmonary compliance, they assessed the correlation coefficient, using a computer. The value of the coefficient is postulated as the extent of obstruction. It can be also used for evaluation of the therapeutic effect and as a prognostic factor. PMID- 2224988 TI - [The effect of controlled hypotension on kidney function in spinal surgery]. AB - The authors investigated the influence of controlled hypotension on renal function in patients operated on account of idiopathic scoliosis of the spine. The deformity was corrected by posterior fusion with Harrington instrumentation under general anaesthesia during controlled hypotension induced by sodium nitroprusside (n = 20). The control group was formed by 20 patients with the same deformity and the same surgical procedure without hypotension. The renal function was assessed before operation, during operation and continuously for 102 hours after operation. In the group of patients with controlled hypotension (median arterial pressure 8.0 kPa) during operation a significant decline of the creatinine clearance occurred (0.7 ml/s), as compared with the control group (1.3 ml/s), as well as compared with the value before operation (1.7 ml/s). After terminated hypotension the mean value of creatinine clearance rose to 2.0-2.2 ml/s for a period of 42 hours. In the control group the creatinine clearance persisted at a slightly reduced level, recorded during operation, for another 30 hours. Sodium retention as a manifestation of hyperaldosteronism was less marked in patients with controlled hypotension. During the investigation period no biochemical signs of retention of nitrogenous substances were recorded. PMID- 2224989 TI - [Vulvoplethysmographic reaction in homosexually-oriented women]. AB - The author examined, using an electrocapacitance VPG apparatus, 50 women reporting homosexual orientation. The results were compared with a control group of 50 women volunteers who reported a defined heterosexual orientation and had no marked complaints and problems in their sexual life. The general vasomotor reactivity in response to erotic stimuli did not differ in the two groups of women (the number of recorded vasomotor reactions differed only insignificantly). During evaluation of the total number of positive reactions to heterosexual and homosexual categories of stimuli the difference between the two groups was highly significant (similarly as during evaluation of the number of positive reactions which were described as major reactions). Women of the homosexually oriented group responded as expected, significantly more frequently and more markedly to homosexual stimuli. As compared with the control group of heterosexually oriented women, they had a generally poorer capacity to differentiate between different categories of erotic stimuli and a lower reactivity during projection of slides of homosexual partnership activities than during projection of slides of homosexual objects (nudes). In all examined women of the control group an unequivocal heterosexual orientation was recorded, in the group of homosexual women a more or less defined homosexual orientation was confirmed. In both groups was a high correlation between the subjectively reported sexual orientation and the results of the VPG examination. The authors confirmed that it is possible to use electrocapacitance vulvoplethysmography as evidence of the homosexual orientation in women and that this psychophysiological examination method is relatively reliable in the diagnosis of female homosexuality. PMID- 2224992 TI - [Comments on heart transplantation in Czechoslovakia]. PMID- 2224990 TI - [HLA antigens on erythrocytes. III. Detection using the absorption and bromelin test]. AB - HLA antigens on erythrocytes were assessed concurrently by three tests--the indirect antiglobulin, two-stage bromelin and absorption test--using polyspecific and monospecific sera against HLA antigens A1, A2, B7, B8 and B12. Evidence obtained by the bromelin test was successful only in rare instances. The positivity of the absorption test increased with the number of saturations: after triple saturation of the HLA serum with erythrocytes of the same subject readings were obtained twice to three times more frequently than after single absorption. As compared with the indirect antiglobulin test, the positive erythrocyte reactions in the absorption test were less frequent: with polyspecific HLA sera in 36.97% as compared with 78.15%, with monospecific HLA sera in 63.64% as compared with 100%. The absorption test is a suitable method for detection of HLA antigens on erythrocytes, supplementing the indirect antiglobulin test. PMID- 2224991 TI - [25 years since the death of Dr. Albert Schweitzer]. PMID- 2224993 TI - [Adverse trends in the development of mortality in lung cancer in the Czech Republic]. AB - The mortality from malignant tumours of the respiratory system in men in the Czech Republik increased steeply during 1950-1967 from the initial value of 22.3 per 100,000 men to more than triple, while in women the values persisted during this period with minor accidental deviations at a level of cca 5.7 per 100,000 women (with standardization for the world population). During the subsequent 20 year period there was a rising trend in both sexes; in 1987 the value for men was 77.4 per 100,000, for women 9.1 per 100,000. The age-specific mortality from malignant tumours of the respiratory system had in none of the evaluated age groups of men and women a declining trend, while in the USA and in Great Britain in younger men and in the group of youngest women a decline is recorded. The cigarette consumption in the Czech Republic after the Second World War increased steeply to the end of the sixties; in 1971-1987 it did not rise further and varied mostly within the range of 19 and 20 billion cigarettes per year, i. e. 2500 cigarettes per inhabitant above 15 years of age, regardless whether he smoked or not. To change the hitherto adverse development of mortality from malignant tumours of the respiratory system it is essential to reduce in the first place the intoxication of the population with carcinogens of tobacco smoke, by influencing smoking habits and by reducing carcinogenic substances in cigarettes and by some modifications of the working and living environment, by provision of an optimal content of probably protective substances in foods and some other measures. PMID- 2224994 TI - [Risk factors in persons with early manifestations of ischemic heart disease and in their offspring. I. Hyperlipoproteinemia]. AB - In a group of 70 probands affected with ischaemic heart disease before the age of 55 years and in their 126 grade I and 8 grade II offspring the ratio of risk factors of the disease was assessed. In the first part of the investigation attention was focused on the frequency of hyperlipoproteinaemias. Elevated total cholesterol and/or triacylglycerols were found in 41% of the probands and 6.4% of the grade I offspring. The most frequently diagnosed type of hyperlipoproteinaemia in probands as well as their offspring was hypertriacylglycerolaemia. Twenty-five per cent of the hyperlipoproteinaemic probands had also a hyperlipoproteinaemic grade I offspring. The author emphasizes that early active screening of offspring of subjects suffering from ischaemic heart disease in young age is essential, in particular those where one of the risk factors is hyperlipoproteinaemia. PMID- 2224995 TI - [Risk factors in persons with early manifestations of ischemic heart disease and in their offspring. II. Additional risk factors]. AB - In a group of 70 probands treated on account of ischaemic heart disease manifested before the age of 55 years and in the grade I and II offspring the presence of other risk factors of the disease was assessed--smoking, arterial hypertension, obesity and diabetes mellitus. This part II is a continuation of the previous paper where the ratio of hyperlipoproteinaemias in the group was assessed. The probands comprised 62.9% smokers, 25.7% hypertonic subjects, 68.6% obese subjects and 20% diabetics. Risk factors were found only in grade I offspring--29.4% smokers, 2.4% hypertonic subjects and 16.7% obese subjects. The author emphasizes the fact that almost 40% of the offspring under 35 years of age with a family-history of early ischaemic heart disease have at least one risk factor of the disease. PMID- 2224996 TI - [Comparison of plasmatic and renal clearance of lithium]. AB - The authors elaborated a method for assessment of the renal lithium clearance, CLr, the results of which correlate well with the plasmatic clearance (CLp] (r = 0.785, p less than 0.05). This correlation improved substantially after correction of CLr to the clearance of endogenous creatinine, CLcr (r = 0.945; p less than 0.05). The mean values of CLr of the investigated group--26.4 ml/min are in agreement with the results published by other authors. A significant correlation between CLr and CLcr (r = 0.826, p less than 0.05) along with comparison of the intraindividual variability of assessed results indicates that it is better to use as a parameter of sodium absorption from the proximal tubule the fractional lithium clearance rather than absolute values of CLr. PMID- 2224998 TI - [Physician-martyrs of the Czech resistance during World War II. I]. PMID- 2224997 TI - [How can the Williams-Beuren syndrome be recognized?]. AB - In a girl with Williams-Beuren's syndrome psychological examination revealed mental retardation with a special mental profile, angiography revealed peripheral pulmonary stenoses, echocardiography a slight stenosis in the supravalvular aortal area and anthropometry typical facial signs. Indirect signs of hypercalcaemia were clinical signs of poor progress during infancy. The authors emphasize that accurate analysis of basic clinical signs and the natural development of the disease are the key to its diagnosis. PMID- 2224999 TI - [The use of Bayes' theorem in controlling the coming epidemic peak of epidemic meningitis in the 1980s]. AB - To control the coming epidemic peak of epidemic cerebrospinal meningitis (ECM) in the 1980s in the regions with 100 million population in China, the mathematical models based upon Bayes' theorem (BT) were established and used respectively in provincial, regional and county's level. Reports of ECM from each ten-day's period or each month during the meningitis season were analysed to create forecast models. Records of ECM vaccinating rate in previous years were fully taken into account to modify the theoretical values. Calibration, split-sample, random-sample selection, as well as actual forecast tests, were used to check the efficiency of the models. The distribution of meningitis vaccine was planned according to the final predictive results. The incidence rates of ECM of above regions decreased obviously faster than other areas in China. Attributing the application of BT forecast research, it was estimated only in Henan province 79795 ECM cases; 4388 deaths and 21 million Yuan economic damage were avoided during the 4 years period, from 1985 to 1988. PMID- 2225000 TI - [An outbreak of epidemic bronchiolitis]. AB - During January to March in 1986, there was an outbreak of epidemic bronchiolitis in Yunchen, Shanxi province. Thirteen counties and cities were involved in Yunchen. On the basis of a survey in 7 counties, there were 6070 cases, with the attack rate of 13.77%. Most patients were infants and young children. The highest attack rate was in 0-age-group (89.06%), next was in 1-age-group (55.71%). The attack rate decreased with the increase of age. The lowest attack rate was in the 10-age-group (0.53%). The attack rate in males was higher than that in females (chi 2 = 101.09, P less than 0.01), and the sex ratio (males to females) was 1.4:1. The clinical symptoms of most patients were serious. Most patients (75.7%) had symptoms of obstructive asthma. In this outbreak, the fatality rate was one percent. Family aggregation of this outbreak of epidemic bronchiolitis was found by binominal distribution method (chi 2 = 9.51 P less than 0.05). Both etiologic and serologic studies showed that the major pathogen causes this epidemic bronchiolitis was RSV. The risk factors in this outbreak were studied. It appeared that the outbreak of epidemic bronchiolitis was related to the variation of temperature: the bigger variation of daily temperature, the more the cases were found (rs = 0.4799, P less than 0.05). The occurrence of the disease was also related average space in the house each person had. The smaller the house, the higher attack rate it showed (trend chi 2 = 5.58, P less than 0.05). PMID- 2225001 TI - [The seroepidemiological observation on hepatitis delta virus infection]. AB - To assess the relationship between hepatitis delta virus (HDV) infection and HBV and reveal the distribution of HDV infection and the feature of epidemic, we collected 271 cases of HBV infected people in Shijiazhuang area and tested anti HD with EIA from April 1987 to October 1988. This study found the prevalence of HDV infection was as high as 12.92% (35/271), and male prevalence of anti-HD was 14.06% (27/192) and female 10.13% (8/79), but there was no significance difference (P greater than 0.05). This suggested that the area of Shijiazhuan was a spot where HDV infection was high. Among these people, the positive rate of anti-HD in chronic active hepatitis, chronic persistent hepatitis and cirrhosis was much higher than that in HBsAg carriers. These finding indicated that HDV infection (coinfection and superinfection) was important in pathogenesis of chronic hepatitis B and in exacerbating liver disease to cirrhosis. This study confirmed that there was no significant difference between HDV infection and age, sex and occupation among HBV infected people. PMID- 2225002 TI - [Quantitative epidemiological investigation on social, economic and geographic factors contributing to falciparum malaria in southern Henan province]. AB - A case-control study was conducted at Xinyang prefecture, Henan province in 1988 to investigate social, economic and geographic factors believed to be associated with the occurrence of residual falciparum malaria cases. Data were obtained from 65 residual cases and 195 matched control samples from neighbours, residents in the same village and extravillage. The questionnaire contained a total of 27 relevant items. The results of analysis of conditional logistic multi-regression model with IBM PC/XT microcomputer showed that six important risk factors related to residual falciparum malaria cases, i.e., the type of breeding places, yellow brown soil, the knowledge of malaria transmission, open-sleep habit, family's malaria history and number of livestock. The epidemiological significance of these findings was discussed briefly. PMID- 2225003 TI - [Conditional logistic regression analysis and path analysis of risk factors of cervical cancer]. AB - A case-control study of 125 pairs was carried out in Jinan during 1987-1988. 39 variables were analysed with the single factor analysis, 14 factors were confirmed as the suspicious risk factors. Conditional Logistic regression analysis of the above 14 factors was used. Results showed that the following five risk factors were associated with cervical cancer, i.e., cervical erosion, low family income, poor personal hygiene during menstrual period, sexual factors and early age at marriage. The causal model with 9 risk factors of cervical cancer was set up and studied with path analysis. The result indicated that 4 risk factors had direct and indirect influence on the occurrence of cervical cancer respectively. PMID- 2225004 TI - [Research into risk factors of bladder cancer in Heilongjiang]. AB - This article reports a 1:2 matched case-control study on 80 cases of bladder cancer in Heilongjiang province. Multiple logistic regression analysis for risk state suggested that three factors, i.e., cigarette smoking, use of saccharin and reduced intake of vegetables are closely associated with development of bladder cancer. Giving up smoking, using no saccharin and eating more fresh vegetables are main ways to reduce the incidence of bladder cancer. PMID- 2225005 TI - [Isolation and identification of the W-88 strain of spotted fever group rickettsiae from a human case in Tongliao City, Inner Mongolia]. AB - One strain of spotted fever group (SFG) rickettsiae was isolated from a patient with febrile and headache who was missdiagnosed as common cold. The rickettsia was isolated by inoculation of yolk sacs of embryonated hen eggs with the patient's blood. The isolate was named as W-88 following the initial letter of the patient's name. It is the first time to report the isolation of SFG rickettsiae from human being who lived in city in China. In this study we compared the antigens of W-88 strain with seven prototype strains of SFG rickettsiae and six Chinese strains of SFG rickettsiae with one species-specific monoclonal antibody and one group reactive monoclonal antibody by indirect immunofluorescence assay. The results demonstrated that W-88 strain and other Chinese strains JH-74, An-84, FT-84, MT-84, Se-85, To-85 of SFG rickettsiae were found identical to Rickettsia sibirica (strains 232 and 246) and differ from other prototypes of SFG rickettsiae. PMID- 2225006 TI - [Study of factors associated with preterm delivery]. AB - A case-control study of preterm delivery was undertaken at the district of Qiaokou in Wuhan during October, 1987 to May, 1988. The study population consisted of 130 mothers of singleton preterm infants and 260 mothers of singleton term infants. The result of logistic regression analysis showed that significant factors of preterm delivery included low maternal stature, the young age of menarche, a previous induced abortion, a history of infertility problems, vaginal bleeding during the pregnancy, low weight gain during the pregnancy, premature rupture of membranes, hyperemesis gravidarum, and lack of antenatal care. The result also showed that psychosocial stress in pregnancy might be related to preterm delivery. PMID- 2225007 TI - [1:2 matched case-control study of congenital deficiency of newborn]. AB - Among 5959 perinatal newborn, 135 cases of congenital deficiency were detected. The frequency was 22.66 per 1,000 newborns. In order to explore possible factors related to congenital deficiency, for 103 cases a 1:2 matched case-control study was performed. Mantel-Haentel chi 2 test and conditional logistic regression model was used to identify factors which associated with the disease significantly in statistics. It was found that six factors, i.e. common cold and fever in the early stage of pregnancy, illiteracy of mother, family history of congenital disease, haemorrhage of genital tract, alcohol drinking and marriage within blood relatives, are risk factors related to congenital deficiency of newborn. PMID- 2225008 TI - [Plasmid DNA transformation of Yersinia pseudotuberculosis by electroporation]. AB - Rendering cells permeable to DNA molecules, electroporation involves the application of high intensity electric fields of short duration to reversibly change the biomembranes, which has been used successfully in some species of both gram negative and positive bacteria. We first reported the electro-transformation technics of Yersinia pseudotuberculosis. The plasmid pJGX20 was constructed by cloning the 9.5 kb plasmid encoding pesticin into Pst I site of pBR328. Transformation efficiency of 103 transformants/micrograms DNA was obtained at voltage of 1300V or 1400V, capacity of 25 microF, time constant of 48-52 msec, with 10% glycerol as electroporation buffer. The pesticin gene of pJGX20 was expressed well in Y. pseudotuberculosis. PMID- 2225009 TI - [Establishment and application of serologic diagnosis method in human immunodeficiency virus]. AB - Using immunoenzymatic method (IE) for human immunodeficiency virus type 1 (HIV-1) serologic detection, and comparing with indirect immunofluorescence method (IIF). This method had same specificity and reproducibility but more sensitivity than IIF. Because it is simple, practical and suitable, IE method can replace IIF as the HIV serologic screening method suited to base application. Using HIV-1 immunoenzymatic reagent kit in Ivory Coast obtained good results. PMID- 2225010 TI - [Passive hemagglutination assay (PHA) in detection of antibodies against measles]. AB - By using passive hemagglutination test and hemagglutination inhibition test, 1771 specimens of sera from healthy people were simultaneously tested. The titers of antibodies against measles GMT were respectively 52.54 and 25.22. The related coefficient was 0.71. P less than 0.001. When the two methods were used to 77 children, the rate of active conversion was 97.40%. When the two methods were used to 28 patients suffering from measles, they gave out same results. PMID- 2225011 TI - [Advances in the research of pathogenicity of Campylobacter pylori and epidemiology of its infection]. PMID- 2225012 TI - The role of fiberoptic transbronchial lung biopsy in diagnosis of chronic infiltrative pulmonary disease in Nigeria. AB - Over a three-year period, fibreoptic transbronchial lung biopsy (FTLB) was performed in 28 adult Nigerian patients with chronic infiltrative lung disease after sputum examination, haematological, biochemical and serological tests failed to provide a definite diagnosis. Definitive histological diagnosis was obtained in 11 patients (39.3 per cent) while another seven (25 per cent) had distinct histological abnormalities but no specific diagnosis. Tuberculosis and sarcoidosis were the commonest findings. No patient had haemorrhage of more than 50mls while only one had asymptomatic mild pneumothorax. FTLB is very safe and spares a substantial proportion of patients with chronic diffuse lung infiltrates more invasive and expensive diagnostic procedures. This is especially very relevant in developing countries where there is a shortage of surgeons, theatre space and other relevant facilities. PMID- 2225013 TI - An approach to the management of volvulus of the sigmoid colon. AB - The colon involved with the sigmoid volvulus is much thicker than the normal colon. It is easy to handle and holds sutures well. Patients who have sigmoid colon volvulus do not have much faecal loading. Most of the distension is gaseous. In the hands of experienced surgeons primary anastomosis can be done after sigmoid colectomy with safety and excellent results. PMID- 2225015 TI - The system of health services planning in Zimbabwe. PMID- 2225014 TI - Carcinoma of the thyroid at Harare histopathology laboratory (Zimbabwe). AB - The carcinoma of the thyroid gland seen at Harare Histopathology Laboratory (Zimbabwe) has been reviewed and analysed. There was a male to female ratio of 1:4. The commonest histological type of tumour was follicular carcinoma (70%). There were equal numbers of papillary and anaplastic types (14% each). Only two cases of medullary carcinoma were found, one of these being in a twelve-year-old female patient. The finding of a high occurance of follicular carcinoma is consistent with Zimbabwe being a country where endemic goitre is common. PMID- 2225016 TI - Neuro anaesthesia--a review of the basic principles and current practices. AB - The changes in intracranial pressure which occur following a change in one of the constituent volumes within the skull are governed by the Monro-Kellie doctrine, stated in the late 18th century and describes how an increase in one of the constituent volumes must be reflected by a reciprocal decrease in another volume to avoid any change in pressure and that if this does not occur, there is a rapid rise in intracranial pressure. Cerebral blood flow is affected by many physiological and pharmacological factors, and is relevant as a change in cerebral blood flow results in a similar alteration in cerebral arterial volume which will affect intracranial dynamics. Another important concept to be understood is cerebral perfusion pressure, how it is related to intracranial and arterial pressures and its relevance during the conduct of any neuroanaesthetic. Both carbon dioxide and the volatile agents are potent vasodilating agents and will cause a catastrophic rise in intracranial pressure and fall in cerebral perfusion pressure if hypercapnia develops in the presence of more than one MAC of a volatile agent. The volatile agents are reviewed and it is stressed that while isoflurane may have advantages over the older volatile agents it is not without complication and nitrous oxide which has always been regarded as an innocuous agent may also have some significant intracranial affects. The use of propofol, as an infusion and the neuromuscular blocking agents and narcotics are described. Recently the use of induced hypotension during clipping of cerebral aneurysms has been questioned and this view and the treatment of vasospasm is discussed in some detail.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225017 TI - The "string-sign" in sonographic diagnosis of diamniotic twin pregnancy. AB - A consistent echogenic line, the "String-sign" resulting from opposed amniotic membranes in diamniotic twin pregnancy as seen at sonography is reported. The string sign is especially useful in the detection of unsuspected twinning in late pregnancy and it should be taken as a definite pointer to multiple pregnancy whenever its presence is established at any stage in pregnancy. PMID- 2225018 TI - Acute suppurative thyroiditis in a malignant thyroid gland. AB - A case of acute suppurative thyroiditis in a malignant thyroid gland is presented. The patient was an elderly woman with several years' history of pre existing goitre. A diagnosis of acute suppurative thyroiditis was not difficult to make because clinical features of an infected thyroid swelling appeared obvious. With the help of intravenous antibiotics and early incision and drainage the patient did well and is now receiving radiotherapy. PMID- 2225019 TI - Gall bladder disease as seen in a Harare referral hospital centre. AB - A five-year study of patients treated for gall bladder disease in Harare was done from 1984-1988. The aim of the study was to highlight the importance of the disease and its unusual presentation as compared to the typical European pattern. The disease is relatively uncommon since only 54 patients were treated while the total hospital admission for the period was 41,891. The disease affected mainly middle-aged housewives. The patients tend to present as semi surgical emergencies. Diagnosis was made most often by Ultrasound scan (U/S) and oral cholangiogram. A few patients had radio opaque gall stones. The majority of the patients, 33, had straightforward cholecystectomy. Ten needed exploration of common bile duct (ECBD) and four were difficult enough to need ECBD, Duodenotomy and sphincterotomy. Operative complications were few considering the mode of presentation. Two patients died, a mortality rate of 3.7 percent. PMID- 2225020 TI - Incidence and parametric determinants of post-operative wound infections in a university teaching hospital. AB - The incidence and determinants of post-operative wound infections in the University of Nigeria Teaching Hospital, Enugu was studied. During the period of study (July 1983-June 1984) 218 surgical operations from adult males and females were investigated. The overall infection rate was found to be 27.98 percent. The incidence rate in clean wounds was 14 percent; in clean-contaminated 50 percent; in contaminated 66.66 percent and in dirty wounds 80 percent. Factors such as age, sex, nature of surgery, and antibiotic prophylactic cover which were found to have influenced the infection are discussed. The study underlines the need for a policy that will promote a more rational use of antibiotics, strict observance of ward aseptic routines and the establishment of effective Infection Control Programme where non exists. PMID- 2225021 TI - Ceftriaxone in the treatment of septicaemia due to multiple drug resistant bacteria. AB - Ceftriaxone, a highly effective, B-Lactamase resistant broad spectrum parenteral cephalosporin was used in the treatment of 26 consecutive patients with clinically and/or bacteriologically resistant infections at the Addis Ababa University Tikur Anbessa and Ethio-Swedish Paediatric Teaching Hospitals. The patients who had failed to respond to a combination of two or more previously appropriate antibiotics were treated with ceftriaxone administered in two divided doses (daily 50-100 mg/kg) in children and a single dose of 2-3 gm in adults for an average duration of 9.9 days. Of the 21 evaluable cases 16 (76%) were cured, three died and two developed superinfection with Pseudomonas and Staphylococcus species. Primary pathogenic bacteria were eradicated from all the 21 bacteraemic patients on the third day of therapy. Twelve of the 21 patients had serious underlying conditions. Except for the two superinfections, the results of the trial confirm that ceftriaxone is a very potent and effective agent in the treatment of resistant bacteraemic infections. No significant adverse effect of the drug was encountered during the therapy. PMID- 2225022 TI - Therapeutic review: antibiotic prophylaxis for bacterial endocarditis. AB - A recent survey of antibiotic prophylaxis found that local practice often differed from that recommended by authoritative bodies such as the British Society for Antimicrobial Chemotherapy (BSAC) and the American Heart Association (AHA). Practitioners found the subject confusing and requested guidance. For these reasons we present current recommendations. Unfortunately all recommendations are based on animal studies and an understanding of the pathogenesis of bacterial endocarditis in humans. There are no controlled trials in humans on which to base guidelines, so rigidity is inappropriate. It is also important to realise that optimal prophylaxis will not eliminate bacterial endocarditis. In developed countries it has been estimated that only 10% of cases of endocarditis are theoretically preventable. PMID- 2225023 TI - Essentials of open heart surgery. AB - As Parirenyatwa continues its successful OPEN-HEART SURGERY PROGRAMME, it becomes important to emphasize that the essential determinants for cardiac surgical success include a comprehensive preoperative assessment of the patient; accurate definition of the fundamental lesion; ameliorative treatment of secondary effects such as cardiac failure, electrolyte imbalance and arrhythmia. In addition to the application of technical expertise in the performance of the operation, an optimal outcome depends on good intraoperative anesthetic management, the collaboration of pump technicians, and dedicated intensive care management in the postoperative period. PMID- 2225024 TI - Fracture of bone with an aneurysmal bone cyst during lactation. AB - A case is presented of a 28-year-old lactating Nigerian mother who developed a pathological fracture of the left humerus following inapparent physical stress. There was radiographical and histological evidence of aneurysmal bone cyst disease involving both humerus. A possible pathogenetic role of bone-calcium dyshomeostasis during pregnancy and, indeed, lactation is entertained. A strong case is made for calcium supplementation in the pregnant and/or lactating mother, especially in the developing countries with an increased probability of marginal nutrition status. PMID- 2225026 TI - Beware the scorpion parabuthus. PMID- 2225025 TI - Effects of two pulmonary tuberculosis drug treatments and acetylator status on liver function in a Zimbabwean population. AB - In Zimbabwe patients with pulmonary tuberculosis who are acid-fast bacilli (AFB) negative in the sputum are treated in the two month intensive phase with isoniazid, thiacetazone pyrazinamide and streptomycin (regimen A). Sputum positive patients receive regimen A plus rifampicin (regimen B). Both groups continue treatment with isoniazid and thiacetazone. 21 patients on regimen A and 19 on regimen B had clinical assessment and liver function tests performed at weeks 0, 2, 4, 8, and 12 weeks of treatment (during and four weeks after, the intensive phase of 8 weeks). Acetylator status was also assessed, no significant difference was found between patients on regimen A or B (41 per cent and 45 per cent fast acetylators respectively). Liver function tests results (alanine aminotransferase and alkaline phosphatase) showed a persisting rise during the intensive phase on both regimens, and further rise after four weeks in the continuation phase, this further rise reaching statistical significance in regimen B. These results are unexpected when compared to other studies but the regimens under investigation are not used elsewhere. The significant rise after stopping intensive therapy in regimen B suggests some protective effect of rifampicin against the hepatotoxicity of the regimen, possibly the isoniazid/thiacetazone component. Acetylator status did not influence the degree of hepatotoxicity. PMID- 2225027 TI - Seasonality of births in the North West Province, Cameroon: implications for family planning programme. AB - This article presents an analysis of the seasonal variation of births between 1978 and 1987 (10 years) in the North West Province. A total of 157,316 births were recorded during the 10 years in question. Highest delivery peaks noticed in the second half of the year for 8/10 years. This gives conception peaks between October and March. Minimum for all the 10 years taken together occurs in July while maximum occurs in September. Considering 40 weeks as normal gestation period, conception peak for the 10 years taken together occurs in December. This peak is related to the festivities that take place within this month. The findings have important implications for family planning. Family planning education needs to be intensified during the period of highest conception or that which leads up to it. PMID- 2225028 TI - Onchocerciasis prevalence in Tanzania. AB - Prevalence of human onchocerciasis in Tanzania is described. The prevalence is high in Bwakira (63.6 per cent), Mahenge (58.6 per cent) and Ruvuma (31.9 per cent); and low in Amani (22.4 per cent) foci when compared to that reported in 1970. The increase and decrease on the prevalence indicate that the disease transmission has been increasing and decreasing in the respective foci. It is speculated that bush clearing and deforestation in general, has positive effects on the transmission of onchocerciasis where Simulium damnosum complex is a vector and negative effects where Simulium neavei complex exists. PMID- 2225029 TI - Mandibular fractures, analysis of 541 cases. AB - A retrospective analysis of 541 patients with mandibular fractures seen at Harare Central Hospital, Harare, Zimbabwe, was undertaken. The aetiology, sex incidence and anatomical sites of fractures are different from those in other series; with 89.8 per cent of the fractures due to assaults, 5.6 per cent due to road traffic accidents; 90.9 per cent of the patients were males, the body of the mandible being most commonly fractured, 42.3 per cent. PMID- 2225030 TI - Catheterization of coronary artery bypass graft from the descending aorta. AB - The increasing frequency of reoperation for coronary artery disease has led to the use of a variety of grafts. This report describes the catheter technique for selective opacification of a saphenous vein graft from the descending thoracic aorta to the posterior coronary circulation. PMID- 2225031 TI - Coronary angioplasty of anomalous coronary arteries: notes on technical aspects. AB - Five patients with significant atherosclerotic lesions of anomalous coronary arteries underwent coronary angioplasty of the anomalous vessel. Four patients had anomalous circumflex artery and 1 had an anomalous right coronary artery. Angiographic and clinical success was achieved in all 5 patients. To ensure adequate equipment selection special consideration should be given to angiographic characteristics of these vessels, such as the orifice configuration, exit angulation, the route the artery traverses and the location of the stenotic lesions. Major determinants for successful angioplasty in these patients are guiding catheter selection and advancement of the balloon catheter to the very proximal portion of the anomalous vessel to subsequently facilitate guide wire advancement. This data indicates that balloon angioplasty can be successfully utilized in patients with significant atherosclerotic disease of anomalous coronary arteries. PMID- 2225033 TI - Angioplasty of occluded coronary arteries: use of thin shaft balloon over-the wire system without pre-dilatation. AB - A retrospective review was done on 13 consecutive patients who underwent PTCA of totally occluded coronary arteries using a recently released thin shaft balloon over-the-wire angioplasty system. Balloon size was determined by the closest fit to the arterial size and used without predilatation techniques. This technique was initially successful in 12 patients with only 2 clinically insignificant episodes of distal embolization and one probable early reclosure. Using thin shaft angioplasty systems, balloon dilatation of totally occluded coronary arteries can be done safely with a single balloon in many cases resulting in simplified procedures and economic benefits. PMID- 2225032 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: I. The stenotic aortic valve. PMID- 2225034 TI - Probe angioplasty of total coronary occlusion using the Probing Catheter technique. AB - Coronary angioplasty (PTCA) of total coronary occlusion is limited by the inability of guidewires and conventional dilating catheters to cross all such lesions. A new technique was therefore prospectively evaluated for PTCA of these lesions using the ultra-low-profile Probe "balloon on a wire" device. An intracoronary Probing Catheter was used to facilitate crossing the stenosis with a guidewire and then to deliver a Probe into the obstruction for balloon dilatation. This technique was utilized in 64 consecutive patients with "absolute" coronary occlusions demonstrating no angiographically detectable antegrade coronary flow. Successful dilatation was achieved in 47 (73%). Among 33 occlusions of less than 3 mo duration 31 (94%) were successfully dilated whereas only 16 of 31 more chronic occlusions were dilated (P less than .01). Chronic occlusions with a tapered morphology and those located more than 1 cm from a branch point were more frequently dilatable. There were no serious complications including no vessel perforations with this technique. The Probing Catheter technique offers a safe and effective method for the dilatation of recent coronary occlusions by using balloon on a wire technology. PMID- 2225035 TI - Anomalous aortic origin of the left anterior descending coronary artery with dilated cardiomyopathy. PMID- 2225037 TI - Angiographic quantitation of the results of coronary angioplasty: where do we stand? PMID- 2225036 TI - Hydrogen test for the detection of left-to-right shunting. PMID- 2225038 TI - Influence of catheter technology and adjuvant medication on acute complications in percutaneous coronary angioplasty. AB - We report on the complication rates in 660 consecutive coronary angioplasties (725 lesions) performed using four procedures that differed with respect to catheter technology and adjuvant medication. After the PTCA regimen in our laboratory had been changed from conventional steerable systems to the monorail technique, we observed a significant increase in the incidence of transient vessel occlusions from 2.6% to 7.7%, of permanent occlusions from 3.6% to 8.8%, and of intracoronary thrombus-formation from 2.6% to 5.5%. This was associated with the frequent observation of thrombotic material on the partially Teflon coated guidewires. Coronary perfusion with urokinase (1,670-6,670 U/min) lead to a further increase in the complication rates (10.4%/10.3%/6.5%). Our present percutaneous transluminal coronary angioplasty (PTCA)-regimen (monorail technique with P.E.T. balloons, fully silicon-coated guidewires, no urokinase) shows an incidence of 3.8% for intermittent and recurrent coronary occlusions and 1.9% for permanent occlusions. Urokinase did not prevent intracoronary thrombus formation with the monorail technique. Furthermore, we suspect that in the case of PTCA induced regional intimal dissection, fibrinolysis can prevent reestablishment of intima adherence to the vessel wall. Because five procedural deaths were observed in the 212 patients treated with i.c. urokinase as opposed to three deaths in the 448 procedures without urokinase, we feel that i.c. urokinase in PTCA is a potentially harmful regimen. We suggest that the monorail technique should be performed with fully silicon-coated guidewires and without urokinase. PMID- 2225039 TI - Regression of infundibular pulmonary stenosis after successful balloon pulmonary valvuloplasty in adults. AB - Between July 1985 and March 1988, 22 adult patients with congenital pulmonary stenosis underwent balloon pulmonary valvuloplasty. There were 10 males and 12 females aged 16-45 (average 25 +/- 9.9) years. All patients had additional mild to severe infundibular stenosis; 16 were restudied 6-36 (mean 12.6) months later by repeat catheterization. Student's t-test was used for comparison of data. Right ventricular (RV) systolic pressure before dilatation was 84-196 (mean 129 +/- 32.3) mm Hg, and the peak pulmonary gradient (PPG) was 60-176 (mean 111 +/- 33.2) mm Hg immediately after dilatation. The RV systolic pressure dropped to 32 140 (mean 59.2 +/- 27) (P less than 0.001); and PPG dropped to 10-113 (mean 37.8 +/- 26.4) (P less than 0.001), and the infundibular gradient ranged from 8 to 113 (mean 35.1 +/- 25.8) mm Hg. The infundibular diameter, before dilatation, ranged from 2 to 15 (mean 9.5 +/- 4) mm Hg. At repeat catheterization, the RV systolic pressure dropped further to 33-66 (mean 42.8 +/- 9.7) mm Hg and the PPG was reduced to 0-48 (mean 18.4 +/- 10.9) mm Hg (P less than 0.001). The infundibular gradient regressed to 0-34 (mean 15 +/- 8.8) mm Hg (P less than 0.001). The infundibular diameter increased to 8-25 (mean 15.8 +/- 5.4) (P less than 0.001). It is concluded that moderate to severe infundibular stenosis, in adults, can regress after successful pulmonary valvuloplasty. PMID- 2225041 TI - Balloon rupture due to lesion morphology during coronary angioplasty. AB - We report a case of coronary angioplasty of a left anterior descending artery lesion that was complicated by the rupture of three successive balloon catheters. Each rupture occurred as a pinhole jet of contrast into a diagonal side branch, causing subintimal staining. This case demonstrates that balloon rupture may result from lesion morphology. PMID- 2225040 TI - Method of measurement of the cardio-thoracic ratio. AB - The authors describe the use of a table for rapid measurement of the cardio thoracic ratio on a standard PA chest film. The method is free of calculations. PMID- 2225042 TI - Death at cardiac catheterization: coronary artery embolization of calcium debris from Ionescu-Shiley bioprosthesis. AB - The case described is a death due to embolization of calcium debris from a bioprosthesis, dislodged at cardiac catheterization. As more bioprosthetic valves are implanted, and more of them fail long-term with calcification, such complications of the invasive study of these valves may be expected. PMID- 2225043 TI - Unusual case of pacemaker lead migration. AB - Pulmonary artery migration of pacemaker lead is rare and may result in pulmonary emboli originating from the thrombus around the infected catheter and causing multiple pulmonary infarcts. We report an unusual case of pacemaker lead migration to the right pulmonary artery with septic pulmonary embolism. While being treated with intravenous Cefuroxamine, the patient had spontaneous migration of the lead to the left pulmonary artery with subsequent left pulmonary embolism. PMID- 2225044 TI - Percutaneous aspiration of thrombus occluding a saphenous vein graft. PMID- 2225045 TI - Severe mitral insufficiency post-balloon valvuloplasty: the late changes found in a disrupted mitral valve. AB - The case of a 45-yr-old woman who had balloon valvuloplasty for rheumatic mitral stenosis is presented. An anterior mitral leaflet tear occurred as a complication of the procedure. Both partial healing of the anterior mitral leaflet and gradual dilatation of the left atrium occurred which allowed the damaged valve to remain in situ for several months. Some of the late changes which occur after such a complicated valvuloplasty are illustrated here, as this patient eventually required surgery and valve excision for definitive repair. PMID- 2225046 TI - Guidelines for balloon valvuloplasty: credentials and training. PMID- 2225047 TI - Physical examination and echo Doppler study in the assessment of femoral arterial complications following cardiac catheterization. AB - Femoral arterial complications following cardiac catheterization have been well recognized. The development of an inguinal mass in these patients can represent a simple hematoma, a pseudoaneurysm, or an arteriovenous fistula. The utility of the physical examination in diagnosing these complications was assessed by using the echo Doppler study for comparison. This study shows that any single clinical sign should not be used in isolation, but a constellation of physical findings can suggest the correct diagnosis. PMID- 2225048 TI - Inflation pressure requirements during coronary angioplasty. AB - To examine the balloon inflation pressures required for successful percutaneous transluminal coronary angioplasty (PTCA), the maximal inflation pressure required for 477 coronary lesions in 200 consecutive patients was determined retrospectively. When graded balloon inflations just sufficient to achieve full expansion were used, the maximal inflation pressure used was less than or equal to 8 atm in 412 stenoses (86%) and was less than or equal to 10 atm in 463 stenoses (97%). Successful PTCA was achieved in 98% of lesions with a 3.5% major procedural complication rate. In a second group of 100 patients studied prospectively, the inflation pressure required to achieve full balloon expansion was less than or equal to 8 atm in 214 of 232 stenoses (92%) and less than or equal to 10 atm in 228 stenoses (98%). Thus, PTCA of coronary stenoses can be achieved with high success rates and low complication rates when graded inflations to pressures just sufficient to achieve full balloon expansion are performed. Most coronary stenoses will respond to pressures less than or equal to 8-10 atm. PMID- 2225049 TI - Evaluation of catheters and metallic catheter markers as calibration standard for measurement of coronary dimension. AB - Measurement of coronary dimension requires an accurate and reproducible dimensional reference. Angiographic catheters are frequently used for this purpose. We measured the angiographic diameters of a broad range of diagnostic and angioplasty guiding catheters by using two commonly used edge-detection algorithms. Angiographic diameters are significantly less than true catheter outer diameter. Therefore the use of contrast-filled catheters as a dimensional reference may lead to considerable error in vessel measurement with overestimation of absolute dimension. Tables of reference values for multiple catheter as calibration standard, tested under a variety of angiographic conditions. The metallic-tipped marker was found to have a better degree of reproducibility than catheters. These findings have implications for studies employing serial measurements of coronary artery dimension and for the clinical practice of estimating vessel diameter for choice of balloon size during angioplasty. PMID- 2225050 TI - Standby percutaneous transluminal coronary angioplasty for coronary artery bypass surgery. PMID- 2225051 TI - Percutaneous puncture of a nondeflatable coronary artery angioplasty balloon. AB - We report a case in which a balloon catheter became permanently inflated in a coronary artery saphenous vein bypass graft. While still inflated, the balloon was forcibly withdrawn from the graft into the external iliac artery and successfully deflated via percutaneous puncture using a CHIBA needle. PMID- 2225052 TI - Treatment of ventricular tachycardia induced cardiogenic shock by percoronary chemical ablation. AB - Incessant ventricular arrhythmias pose an especially challenging therapeutic dilemma. We describe the successful treatment and follow-up of a patient with refractory ventricular tachycardia-induced cardiogenic shock with percoronary chemical ablation. After endocardial mapping was used to identify the "tachycardia-related" coronary artery, temporary termination of the arrhythmia with balloon occlusion and subselective intracoronary installation of iced saline as previously advocated was unsuccessful. This was probably due to a dual arterial blood supply to the arrhythmogenic focus. However, infusion of 2 cc ethanol (99%) permanently terminated the arrhythmia. Contrary to previous experience, ethanol-induced arrhythmia termination did not result in arterial occlusion, further supporting a direct toxic effect on the myocardium as its mode of action. Use of standard angioplasty balloon inflation prevents "backwash" of distally infused ethanol and more generalized cell death. The only complication of this procedure was temporary third-degree AV block, requiring permanent pacemaker implantation. PMID- 2225053 TI - Percutaneous transluminal coronary angioplasty of gastroepiploic artery graft. AB - The right gastroepiploic artery is being used as a third arterial conduit for coronary artery bypass surgery. Presented here is a case demonstrating successful percutaneous transluminal coronary angioplasty of the gastroepiploic artery graft. This successful accomplishment may avoid repeat surgical revascularization in case of failure of the gastroepiploic artery graft, hence may encourage people to use it more often. PMID- 2225054 TI - Angioplasty of a recently occluded coronary artery bypass graft. PMID- 2225055 TI - Usefulness of digital angiography in the assessment of left ventricular ejection fraction. AB - With modern digital cardiac systems the image data are digitized on-line and in real-time, allowing the replay and subsequent interpretation and analysis during or directly after the cardiac catheterization procedure. In this study we have evaluated the advantages and limitations of a manual tracing technique for left ventricular digital angiograms on the Phillips DCI system. Thirty-three patients who were catheterized for suspected coronary artery disease were studied. The manual tracings were performed by a senior cardiologist and an experienced function-analyst. It was found that the short- and long-term intraobserver variabilities in the assessment of the global ejection fraction were very small; short-term mean difference +/- standard deviation (correlation coefficient): 0.5 +/- 2.7 (r = 0.97) global EF%-units; long term; 0.7 +/- 2.7 (r = 0.96) EF%-units. The interobserver variabilities (5.1 +/- 4.8 (r = 0.93) EF%-units) were slightly higher than the intraobserver variabilities. A decrease by 25% in the amount of contrast medium administered did not significantly influence the variabilities in the contour tracings, which would suggest the use of smaller doses. At the average, the cardiologist and the function-analyst required 6 and 11 min of analysis time for a left ventricular study, respectively, emphasizing the need for further developments towards automated contour detection. Finally, an excellent correlation was found with a standard off-line cinefilm analysis procedure. Thus, it may be concluded that quantitative digital left ventricular angiography based on manual tracing of the outlines performed immediately following the cardiac catheterization (post-processing) is feasible as a routine procedure for the assessment of left ventricular function. PMID- 2225056 TI - Temporary cardiac pacing using a new, steerable, balloon-tipped pacing catheter. AB - A new balloon-tipped, flow-directed, steerable pacing catheter for unipolar temporary ventricular pacing is presented. It was successfully and uneventfully tested in 25 patients with acute myocardial infarction in the coronary care unit. The main advantage of the new catheter is the ease with which a stable contact may be achieved between the pacing electrode and the endocardium. PMID- 2225057 TI - Guidelines for professional staff privileges in the cardiac catheterization laboratory. Laboratory Performance Standards Committee. PMID- 2225058 TI - Exit block or reentry? PMID- 2225059 TI - How do polypeptides cross the mitochondrial membranes? PMID- 2225060 TI - The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? PMID- 2225061 TI - Recent insights in phosphatidylinositol signaling. AB - Studies of phosphatidylinositol signaling pathways are entering a new phase in which molecular genetic techniques are providing powerful tools to dissect the functions of various metabolites and pathways. Studies with phospholipase C are most advanced and clearly indicate that phosphatidylinositol turnover is critical for vision in Drosophila and cell proliferation in various cultured cells. Expression of cDNA constructs and microinjection of PLC or antibodies against it clearly establish a role for PtdIns signaling distinct from its role in calcium mobilization and protein kinase C activation. The importance of inositol cyclic phosphates is also beginning to be realized from the study of cyclic hydrolase using similar techniques. Elucidation of the function of the 3-phosphate inositol phospholipid pathway awaits similar studies. The recent cDNA cloning of inositol monophosphatase (Diehl et al., 1990), Ins(1,4,5)P3 3-kinase (Choi et al., 1990), and inositol polyphosphate 1-phosphatase (York and Majerus, 1991) should provide tools to define further the cell biology of the phosphatidylinositol signaling pathway. PMID- 2225062 TI - Activins are expressed early in Xenopus embryogenesis and can induce axial mesoderm and anterior structures. AB - We show that mammalian and Xenopus activins induce dorsal axial mesoderm and anterior structures in explants of Xenopus blastula cells that would otherwise form epidermis. The induced explants of animal cap cells can form notochord, muscle, neural tissue, and eyes all arranged in a rudimentary axial pattern. Activin A shares inductive properties and antigenic determinants with PIF, an inducing factor recently isolated from mouse macrophage culture supernatants. Genes encoding Xenopus activin beta A and beta B chains were cloned. Activin beta B transcripts are first detected in Xenopus blastula, whereas activin beta A transcripts do not appear until the late gastrula stage. Recombinant Xenopus activin beta B protein induces mesodermal and neural tissues similar to those induced by mammalian activin A and PIF. Furthermore, ectopic expression of Xenopus activin beta B produces a second body axis in embryos injected with synthetic mRNA. Our results suggest that early induction and axial patterning are accomplished by endogenous activin B, not activin A, in Xenopus. PMID- 2225064 TI - Colocalized transmembrane determinants for ER degradation and subunit assembly explain the intracellular fate of TCR chains. AB - The intracellular fate of T cell antigen receptor (TCR) subunits (alpha beta gamma delta epsilon zeta 2) is determined by their assembly in the endoplasmic reticulum (ER). To study the structural bases for this tight correlation between assembly and intracellular fate, we sought to define the nature of determinants for both ER degradation and subunit assembly within the TCR-alpha chain. We found that a 9 amino acid transmembrane sequence of the TCR-alpha chain, containing 2 critical charged residues, was sufficient to cause ER degradation when placed in the context of the Tac antigen, used here as a reporter protein. CD3-delta assembled with chimeric proteins containing this short transmembrane sequence, and this assembly resulted in abrogation of targeting for ER degradation. Thus, the colocalization of determinants for ER degradation and sites of subunit interactions explains how the fate of some newly synthesized TCR chains can be decided on the basis of their assembly status. PMID- 2225063 TI - Activin can induce the formation of axial structures and is expressed in the hypoblast of the chick. AB - We show that PIF/activin can induce the formation of axial structures including a full-length notochord, segmented somites, and a neural tube in isolated epiblasts from chick blastulae. Using degenerate PCR primers, we have cloned a fragment of the activin beta B chain from chick hypoblast cDNA, and a fragment of the activin beta A chain from chick genomic DNA. Furthermore, we show that in the chick, activin is transcribed precisely when axial mesoderm is being induced. Since exogenous PIF/activin can induce the formation of axial structures and since activin beta B is transcribed at the time and place where the mesodermal axial structures are being induced, we propose that in the chick, activin B is the endogenous inducer of the body axis. PMID- 2225065 TI - A role for integrin in the formation of sarcomeric cytoarchitecture. AB - We propose that integrins help to coordinate the differentiation of the internal, sarcomeric cytoarchitecture of a muscle fiber with its immediate environment and are essential for correct integration of muscle cells into tissue. We found that integrin alpha PS2 beta PS accumulated at contact regions of Drosophila embryo cells cultured in D-22 medium on Drosophila laminin. Myotubes formed, but subsequent addition of serum or fibronectin was needed for sarcomere formation: integrin and actin became concentrated at Z-bands; myosin and actin occurred between the Z-bands. This change failed to occur in the multinucleate myotubes derived from integrin beta PS null myospheroid mutants. In normal embryos/early larvae, integrin was located at Z-bands and at muscle insertions. Myogenesis and Z-bands were defective in myospheroid embryos. Attachment, spreading, and growth of myoblasts and neurons on the laminin substrate utilized different binding proteins and were independent of integrin. PMID- 2225066 TI - Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless. AB - armadillo (arm) is one of a group of Drosophila segment polarity genes that are required for normal patterning within the embryonic segment. Although arm RNA is uniformly distributed in embryos, arm protein accumulates at higher levels in regions that contain wingless, another segment polarity gene which encodes a secreted protein that regulates patterning via cell-cell communication. These local increases in arm protein require wingless activity, and mutations that alter wingless distribution produce corresponding changes in the arm protein pattern. These results suggest that wingless regulates accumulation of arm protein by a posttranscriptional mechanism. Two other segment polarity genes, porcupine and dishevelled, are required for this effect. We also show that arm protein is closely associated with the plasma membrane in virtually all cell types and often colocalizes with F-actin. PMID- 2225067 TI - Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. AB - Overexpression of TAR-containing sequences (TAR decoys) was used to render cells resistant to HIV replication. A chimeric tRNA(meti)-TAR transcription unit contained in a double copy murine retroviral vector was used to express high levels of HIV-1 TAR-containing transcripts in CEM SS cells. Replication of HIV-1 was inhibited over 99% in cells expressing chimeric tRNA-TAR transcripts, but an amphotropic murine retrovirus replicated normally in these cells. Expression of TAR sequences in CEM SS cells had no adverse effects on cell viability, indicating that essential cellular factors are not being sequestered in these cells. TAR decoy RNA-mediated HIV inhibition may also be effective against natural HIV isolates in spite of their hypervariable nature, as suggested by the fact that replication of SIVmac was also inhibited in cells expressing HIV-1 TAR decoys. PMID- 2225068 TI - Exon mutations uncouple 5' splice site selection from U1 snRNA pairing. AB - It has previously been shown that a mutation of yeast 5' splice junctions at position 5 (GUAUGU) causes aberrant pre-mRNA cleavages near the correct 5' splice site. We show here that the addition of exon mutations to an aberrant cleavage site region transforms it into a functional 5' splice site both in vivo and in vitro. The aberrant mRNAs are translated in vivo. The results suggest that the highly conserved G at the 5' end of introns is necessary for the second step of splicing. Further analyses indicate that the location of the U1 snRNA-pre-mRNA pairing is not affected by the exon mutations and that the precise 5' splice site is selected independent of this pairing. PMID- 2225069 TI - The HIV-1 Tat protein: an RNA sequence-specific processivity factor? PMID- 2225070 TI - Self superantigens? PMID- 2225071 TI - Globin gene regulation and switching: circa 1990. AB - Suggestions that the field of hemoglobin regulation and erythroid cell molecular biology was undergoing a tortuous and slow death, awash in the scientific community several years ago, were dispelled by the findings presented at the Seventh Conference on Hemoglobin Switching. After a phase in which neither the cis-elements nor trans-factors important for globin and erythroid gene expression were evident, recent progress has been rapid. Once again, studies in this area are providing fundamental insights into eukaryotic biology. The long-distance influence of LCR elements on chromatin structure and gene expression is remarkable and likely to be encountered in the analysis of other developmentally regulated, multigene loci. How LCR elements influence chromatin structure and maintain an open configuration is a problem at the core of gene regulation. We can be optimistic that further dissection of LCRs will delineate DNA sequences critical for these effects and associated proteins. The interaction of LCRs with individual genes must depend on specific protein-protein interactions, most likely involving a small, but elite, group of regulators. At least one critical transcriptional regulator of erythroid-expressed genes, GATA-1, is firmly established. Others are being pursued. The mechanisms by which they collaborate with each other should provide the missing pieces to the puzzle of cell-specific gene expression in the erythroid lineage. As the phenomenology of Hb switching is mimicked in transgenic mice, the elements mediating competitive and non competitive (or autonomous) modes of regulation will be systematically delineated. Whether knowledge of the cis- and trans- components involved in switching will lead to the development of therapeutic approaches aimed at altering their complex interactions is uncertain. Fortunately, recent progress in hematopoietic stem cell biology once again raises hopes that gene transfer strategies for management of hemoglobin disorders may be more than a distant, impractical goal. PMID- 2225072 TI - The hepatitis B virus-encoded transcriptional trans-activator hbx appears to be a novel protein serine/threonine kinase. AB - To study the functional mechanism of the hepatitis B virus (HBV) X (hbx) gene product, we have expressed the hbx protein in E. coli and purified it by HPLC. The purified hbx protein was shown to be active in transactivating transcription directed by the LTR sequence of HIV-1. The hbx protein was found to have an intrinsic serine/threonine protein kinase activity. The hbx protein was detected in hepatitis B virions, and tryptic phosphopeptide maps of the hbx protein phosphorylated in the virion and of the in vitro phosphorylated bacterially expressed hbx protein were similar. Inactivation of the hbx protein by heat, protein-denaturing agents, or an ATP affinity analog, p-fluorosulfonylbenzoyl 5' adenosine, resulted in loss of both protein kinase activity and trans-activation activity. These results suggest that the HBV-encoded trans-activator hbx is a novel protein kinase. PMID- 2225073 TI - V beta 17 gene polymorphism in wild-derived mouse strains: two amino acid substitutions in the V beta 17 region greatly alter T cell receptor specificity. AB - Of 41 wild-derived mouse strains analyzed, 14 contained T cells bearing V beta 17 receptors in spite of the concomitant expression of I-E antigens. Reciprocal F1 and F2 hybrids of one of these strains, PWK, with laboratory strains revealed different patterns of V beta 17 T cell deletions from those observed with V beta 17 T cells from SJL, implying that the two V beta 17 regions are associated with recognition of distinct superantigens. The structures of the V beta 17 alleles differ by two amino acid substitutions, which lie together in an area distant from the predicted site of T cell receptor interaction with peptide-MHC complexes but overlapping with that implicated in V beta 8.2 recognition of Mls-1 superantigen. This demonstrates that the self-superantigen leading to V beta 17 T cell deletion varies with the allele of the receptor gene and confirms that T cell deletions by such ligands involve interactions with a region of the V beta domain that is distinct from the conventional combining site. PMID- 2225074 TI - RAP1 protein interacts with yeast telomeres in vivo: overproduction alters telomere structure and decreases chromosome stability. AB - The protein encoded by the RAP1 gene of S. cerevisiae binds in vitro to a consensus sequence occurring at a number of sites in the yeast genome, including the repeated sequence C2-3A(CA)1-6 found at yeast telomeres. We present two lines of evidence for the in vivo binding of RAP1 protein at telomeres: first, RAP1 is present in telomeric chromatin and second, alterations in the level of RAP1 protein affect telomere length. The length changes seen with under- and overexpression of RAP1 are consistent with the interpretation that RAP1 binding to telomeres protects them from degradation. Unexpectedly, overproduction of the RAP1 protein was also shown to decrease greatly chromosome stability, suggesting that RAP1 mediates interactions that have a more global effect on chromosome behavior than simply protecting telomeres from degradation. Such interactions may involve telomere associations both with other telomeres and/or with structural elements of the nucleus. PMID- 2225075 TI - Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. AB - S. cerevisiae chromosomes end with the telomeric repeat (TG1-3)n. When any of four Pol II genes was placed immediately adjacent to the telomeric repeats, expression of the gene was reversibly repressed as demonstrated by phenotype and mRNA analyses. For example, cells bearing a telomere-linked copy of ADE2 produced predominantly red colonies (a phenotype characteristic of ade2- cells) containing white sectors (characteristic of ADE2+ cells). Repression was due to proximity to the telomere itself since an 81 bp tract of (TG1-3)n positioned downstream of URA3 when URA3 was approximately 20 kb from the end of chromosome VII did not alter expression of the gene. However, this internal tract of (TG1-3)n could spontaneously become telomeric, in which case expression of the URA3 gene was repressed. These data demonstrate that yeast telomeres exert a position effect on the transcription of nearby genes, an effect that is under epigenetic control. PMID- 2225076 TI - The controlling sequence for site-specific chromosome breakage in Tetrahymena. AB - Site-specific chromosome breakage occurs in many ciliated protozoa during nuclear differentiation. We have determined the cis-acting sequence that controls this process in Tetrahymena thermophila. The Tetrahymena ribosomal RNA gene is bounded by two breakage sites. Injection of this gene into developing macronuclei leads to breakage at these sites. Deletion analysis has localized the sequences essential for breakage to a 28 bp region that includes a 15 bp sequence (Cbs) known to be present in other breakage sites. Insertions of Cbs allow breakage to occur at new sites, which is accompanied by elimination of surrounding DNAs and formation of telomeric sequences, as it is at natural sites. Thus, Cbs is the necessary and sufficient sequence signal for chromosome breakage in Tetrahymena. PMID- 2225077 TI - HIV-1 Tat protein trans-activates transcription in vitro. AB - Tat protein of human immunodeficiency virus 1 is a potent trans-activator of viral gene expression. We show that purified Tat protein stimulates transcription from viral promoters greater than 10-fold in vitro. A Tat protein mutant that does not trans-activate in vivo did not stimulate transcription in vitro. Tat trans-activation required a functional TAR RNA sequence; trans-activation was competed by the addition of in vitro synthesized wild-type TAR RNA but not by mutant TAR RNAs. That Tat protein directly interacts with the TAR RNA during trans-activation in vitro was suggested by competition with Tat peptides. Preliminary evidence suggests the involvement of a cellular factor in recognition of TAR RNA during Tat trans-activation. Analysis of Tat trans-activation in vitro will provide new mechanistic insights into this process and allow a more detailed study of the relationship between Tat protein structure and function. PMID- 2225078 TI - The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF kappa B function. AB - Studies of NF-kappa B suggest that this enhancer binding activity corresponds to a family of at least four proteins (p50, p55, p75, and p85) differentially induced with biphasic kinetics during T cell activation. While p55 and p50 are closely related to the 50 kd DNA binding subunit of NF-kappa B, p75 and p85 exhibit DNA binding properties that distinguish them from this 50 kd polypeptide and its regulatory subunits I kappa B and p65. All four members of this kappa B specific protein family are structurally related to the v-Rel oncoprotein and one, p85, appears identical to human c-Rel. v-Rel, but not nontransforming v-Rel mutants, binds to the kappa B enhancer and inhibits NF-kappa B-activated transcription from the IL-2 receptor alpha promoter and HIV-1 LTR. These findings suggest a Rel-related family of kappa B enhancer binding proteins and raise the possibility that the transforming activity of v-Rel is linked to its inhibitory action on cellular genes under NF-kappa B control. PMID- 2225079 TI - T lymphocyte stress response. II. Protection of translation and DNA replication against some forms of stress by prior hyperthermic stress. AB - We have compared the effects of a mild heat shock and febrile temperatures on heat-shock protein (hsp) synthesis and development of stress tolerance in T lymphocytes. Our previous studies demonstrated that febrile temperatures (less than or equal to 41 degrees C) induced the synthesis of hsp110, hsp90, and the constitutive or cognate form of hsp70 (hscp70; a weak induction of the strongly stress-induced hsp70 was also observed. In the studies reported herein, we demonstrate that a mild heat shock (42.5 degrees C) reverses this ratio; that is, hsp70 and not hscp70 is the predominate member of this family synthesized at this temperature. Modest heat shock also enhanced the synthesis of hsp110 and hsp90. In order to assess the relationship between hsp synthesis and the acquisition of thermotolerance, purified T cells were first incubated at 42.5 degrees C (induction temperature) and then subsequently subjected to a severe heat-shock challenge (45 degrees C, 30 min). T cells first incubated at a mild heat-shock temperature were capable of total protein synthesis at a more rapid rate following a severe heat shock than control cells (induction temperature 37 degrees C). This phenomenon, which has been previously termed translational tolerance, did not develop in cells incubated at the febrile temperature (induction temperature 41 degrees C). Protection of translation also extended to immunologically relevant proteins such as interleukin-2 and the interleukin-2 receptor. Because clonal expansion is a critical event during an immune response, the effects of hyperthermic stress on DNA replication (mitogen-induced T cell proliferation) was also evaluated in thermotolerant T cells. DNA synthesis in control cells (induction temperature 37 degrees C) was severely inhibited following heat-shock challenge at 44 degrees C or 45 degrees C; in contrast, T cells preincubated at 42.5 degrees C rapidly recovered their DNA synthetic capacity. T cells preincubated at a febrile temperature were moderately protected against hyperthermic stress. The acquisition of thermotolerance was also associated with enhanced resistance to chemical (ethanol)-induced stress but not to heavy metal toxicity (cadmium) or dexamethasone-induced immunosuppression. These studies suggest that prior hsp synthesis may protect immune function against some forms of stress (e.g., febrile episode) but would be ineffective against others such as elevated glucocorticoid levels which normally occur during an immune response. PMID- 2225082 TI - The nucleolar chromatin and the secondary constriction. AB - We have traced the nucleolar chromatin from early prophase to the metaphase stage. In prophase this chromatin begins to condense and in metaphase it is fully condensed. In mitotic chromosomes, this chromatin remains surrounded by achromatic materials resembling the fibrillar centre. As such this region of the chromosomes appears as a gap or constriction at the light microscope level. The possible role of this achromatic material in relation to nucleologenesis and satellite association has been discussed. PMID- 2225080 TI - Thymic hormone modulation of age-induced changes in the induction of graft-versus host disease by DBA/2J lymphocytes. AB - Aging induces a number of changes in the immune system, including the involution of the thymus which results in the loss of thymic hormone production and alteration in T cell function. One age-dependent change in immune response is the increasing risk of developing acute or chronic form of graft-versus-host disease (GVHD) following bone marrow transplantation as the age of the recipient increases. A murine model of GVHD that has been extensively studied is one in which injection of C57BL/6 spleen cells into unirradiated B6D2F1 mice results in an acute form of GVHD characterized by cytolytic T lymphocytes (CTL), suppressor cells, runting, and occasionally death. In contrast, injection of DBA/2J spleen cells results in a chronic form of GVHD characterized by a lack of CTL and hyperproduction of immunoglobulin and autoantibodies. This study shows that the GVHD response of DBA/2J spleen cells is dependent on the age of the donor DBA/2J mice. If spleen cells from DBA/2J mice older than 3 months are injected into B6D2F1 recipients, CTL and lack of immunoglobulin production indicative of acute GVHD result. Administration of thymosin fraction 5, a collection of thymic hormones, to DBA/2J mice older than 3 months caused spleen cells from these treated mice to give a GVHD response characteristic of the chronic form of GVHD in B6D2F1 recipients. Thus, thymic hormones were able to modulate the changes in GVHD responses of DBA/2 lymphocytes that occur as the mice age. Preliminary fractionation of TF5 has indicated that there are at least two active thymic peptides present in TF5. PMID- 2225081 TI - Mechanisms of pertussis toxin inhibition of lymphocyte-HEV interactions. I. Analysis of lymphocyte homing receptor-mediated binding mechanisms. AB - The molecular mechanisms by which pertussis toxin (PTX) inhibits lymphocyte homing to peripheral lymph nodes (PLN) remain poorly understood. PTX-treated lymphocytes express homing receptors, yet cannot extravasate into PLN in vivo. Methylation of PTX, a procedure known to inactivate the B-oligomer of the toxin, restored high endothelial venule (HEV) binding capacity. In vitro studies established that toxin exposure inhibited the accessory role of LFA-1 in HEV binding. In contrast, PTX-exposed lymphocytes exhibited normal MEL-14-mediated HEV binding. Analysis of membrane fluidity revealed a 20% decrease in fluorescence polarization in PTX-exposed lymphocytes. On the basis of the current experiments, we propose a "zipper" model of lymphocyte-HEV interaction, in which lateral mobility of adhesion receptors in the cell membrane toward a site of endothelial contact is necessary to maintain adhesion against the shear force due to blood flow. PTX inhibits these processes by decreasing membrane fluidity, and by altering accessory adhesion molecule function. PMID- 2225083 TI - The fluorescent probe BCECF has a heterogeneous distribution in sea urchin eggs. AB - Sea urchin eggs were loaded with the pH-sensitive fluorescent probe BCECF. Homogenization of these eggs, followed by centrifugation, resulted in 25% of the total homogenate fluorescence remaining with the pellet. Fluorescence microscopy revealed brightly fluorescing punctate organelles whose fluorescence was not quenched by acidification. The excitation spectrum of intracellular BCECF was markedly red-shifted compared to probe calibrated in buffer. Model excitation spectra based on a two compartment model mimicked the intracellular BCECF spectrum, therefore, supporting the possibility that organelles in sea urchin eggs accumulate large amounts of BCECF in a relatively pH-insensitive form. PMID- 2225084 TI - Study of fibronectin expression in tumour cells by dot-blot and in situ hybridization: quantitative evaluation by image analysis. AB - An Image Analysis program was used for the quantitative evaluation and comparison of the fibronectin (FN) mRNA detected by dot-blot and in situ hybridization in different cell lines. These techniques were applied for the evaluation of FN mRNA synthesized by human normal fibroblasts (Flow 7000) and by four tumour-derived cell lines (HeLa, epithelioid carcinoma; 8387, fibrosarcoma; RD, rhabdomyosarcoma; SK Hep-1, hepatocarcinoma). Dot-blot analysis showed that the cell types analysed synthesize different levels of FN mRNA. Flow 7000 are the highest producers while HeLa the lowest. In situ hybridization confirmed these results and furthermore showed that while Flow 7000, 8387 and HeLa cells synthesized homogeneous levels of FN mRNA, RD and SK Hep-1 could be subdivided into two populations expressing high or low levels of FN mRNA. The combined analysis of dot-blot, in situ hybridization and Image Analysis allowed the quantitation of the number of FN mRNA molecules expressed by single cells. This approach is therefore an invaluable tool when evaluating mRNA expression in heterogeneous cell populations like tumour-derived cell lines, during cell cycle or in histological tissue sections. PMID- 2225085 TI - Location of nuclear antigen(s) recognized by DSB389 MAb, a monoclonal antibody against desmin, observed by confocal laser scanning fluorescence microscopy. AB - The location of antigen(s) of DSB389 MAb, a monoclonal antibody which was raised against an intermediate filament protein, desmin, was investigated in HeLa S3 cells by indirect immuno-electron microscopy and by confocal laser scanning fluorescence microscopy. At interphase, the antigen(s) locates mainly in the intra-nuclear space adjacent to chromatin and sometimes near the nuclear periphery. At mitosis, they locate at the periphery of the chromosomes -first at each chromosome, then around the mass of chromosomes. The antigen(s) are thought to be a component of one type of nuclear matrix which is present outside both chromatin and chromosomes and which has some structural role(s) in organizing them in the nucleus or in the nuclear region. PMID- 2225086 TI - Immunocytochemical identification of cytoskeletal linkages to smooth muscle cell nuclei and mitochondria. AB - In avian smooth muscle cells, desmin-containing intermediate filaments (IFs) are a prominent component of the cytoskeleton and are readily seen in several domains, including the axial intermediate filament bundle (IFB). Both the nucleus and some of the mitochondria are partly surrounded by elements of the IFB. By using anti-desmin and protein-A-colloidal gold labeling, we have identified intermediate filaments that form linkages with the nuclear envelope and with mitochondria. These linkage regions seem to occupy a proportionately greater part of the mitochondrial surface than of the nuclear envelope. The existence of these linkages in smooth muscle cells is consistent with results that support similar linkages to mitochondria and other cellular structures in various cells that contain either vimentin or keratin IFs. These linkages could functionally restrain or assist in homeostatically restoring organelles to their normal position after the rearrangement that accompanies the substantial shortening of smooth muscle cells. PMID- 2225087 TI - Identification and characterization of a novel mammalian intermediate filament associated protein. AB - A novel monoclonal antibody, designated M1.4, recognizes the high molecular weight microtubule-associated protein MAP1A (ca. Mr 380 kD) in both bovine and rat brain. In HeLa cells, however, M1.4 binds to a 240 kD polypeptide on immunoblots and co-localizes with both vimentin and cytokeratin filaments using double-label immunofluorescence microscopy. Immunoelectron microscopy indicates that the 240 kD polypeptide localizes along bundled intermediate filaments in a periodic manner. Two-dimensional electrophoretic analysis indicates that the 240 kD polypeptide has a basic pI of 7.7. When HeLa cell intermediate filaments are isolated using standard non-ionic detergent/high-salt conditions the 240 kD polypeptide does not sediment with the intermediate filaments, unlike the established intermediate filament-associated protein plectin. Immunoblot analysis with M1.4 shows the 240 kD polypeptide is expressed in a number of mammalian cell lines. Additionally, double-label immunofluorescence shows the 240 kD polypeptide to associate with vimentin filaments in African Green Monkey kidney (CV-1) and JC neuroblastoma cells. Due to its unique biochemical and biological characteristics, the 240 kD polypeptide is clearly a novel intermediate filament associated protein for which we have proposed the designation gyronemin (Gr. gyros: around; nemin: filament). PMID- 2225088 TI - Effects of trypsin and low Ca2+ on zonulae adhaerentes between chick retinal pigment epithelial cells in organ culture. AB - The junctional complexes in chick retinal pigment epithelial (RPE) cells in situ contain unusually large zonulae adhaerentes (ZAs) composed of subunits termed zonula adhaerens complexes (ZACs). To determine whether the properties of the ZAs differ between RPE cells which contain ZACs, and MDCK cells which lack ZACs, we investigated the effects of treatment with trypsin and/or low Ca2+ by transmission electron microscopy and staining for F-actin. Treatment of RPE cells for 1 h with trypsin alone has no apparent effect on the morphology of the ZA in either MDCK or RPE cells. In contrast to the ZAs in MDCK cells, which split after 3 min in low Ca2+, the ZAs in chick RPE cells stay intact even after 2 h, although the intermembrane discs, i.e., the extracellular components of the ZACs, are no longer visible. After 30 min of treatment with trypsin and low Ca2+, the ZAs split in both cell types. The CMBs start to contract, translocate toward the cell interior, and eventually disappear. This process continues even when the RPE cells are returned to normal medium. New ZAs, composed of ZACs, form between RPE cells 3 h after return to normal medium. These findings suggest that the ZACs in the ZAs of RPE cells are not directly responsible for the increase in resistance to low Ca2+. They also show that the ZA-junctions in RPE cells are not only structurally different from those previously examined, but also behave differently in response to experimental manipulation. PMID- 2225089 TI - Behavior of C-shaped microtubule endings in the cell. AB - The association of incomplete microtubule assemblies with either another incomplete structure or complete microtubules was studied in two organisms, the phytoflagellate Polytoma papillatum and the phorid fly Megaselia scalaris, using transmission electron microscopy. In the alga, hook-shaped appendages on cytoplasmic and spindle microtubules were detected. These resulted from the lateral association of a curved ribbon of protofilaments with the surface of a complete microtubular wall. In the fly, an S-shaped protofilament sheet was found embedded in the kinetochore plate of a prometaphase I spermatocyte. Tracing of the S-shaped element towards the spindle pole revealed that it was formed by the lateral junction of two curved protofilament sheets. In all cases, the C-shaped protofilament sheets represented the endings of complete microtubules. Incomplete microtubules are generally considered as representing intermediates of microtubule assembly and disassembly. Since high molecular weight proteins are believed to be responsible for maintaining microtubule-microtubule spacing, it is hypothesized that the endings of growing and shrinking microtubules are sparsely studded with these proteins; their depletion allows lateral microtubule contacts. In addition, the microtubule-microtubule contacts may be rendered possible by the flexibility of the slender elongated microtubule-associated molecules. Relatively long C-shaped protofilament appendages (0.6-1.4 microns) were detected in this study. Therefore, it is plausible to assume that the protofilament sheets are stabilized by contact with one another or with an intact tubule wall. PMID- 2225090 TI - Tension as a regulator and integrator of axonal growth. PMID- 2225091 TI - Opioid peptides and stress. PMID- 2225092 TI - The role of endogenous opioid peptides in the regulation of pain. PMID- 2225093 TI - Central stimulation-induced analgesia in humans--modulation by endogenous opioid peptides. AB - Stimulation of the endogenous opiate system produced relief of somatosensory induced pain states. Stimulation of the nonopiate system can control pain from somatosensory causes as well as damage to the nervous system. Neither of these systems in themselves are rewarding or produce self-stimulation in humans, who have free choice of whether to use stimulation or not, except to reduce discomfort. Lack of pain in general produces lack of use of the stimulation system. Apparently, the descending opiate system for somatosensory pain control involves descending norepinephrine and serotonin pathways at an intermediate step through the dorsolateral funiculus of the cord. Enhancement of the opiate system can be produced by administration of L-Tryptophan and L-Dopa due to precursor loading of serotonin and norepinephrine. The endogenous opiate system, when activated by electrical stimulation, usually produces excellent control of somatosensory induced pain, but often is not effective for centrally produced pain. Stimulation of areas that produce analgesia that are nonopiate-dependent are usually more effective in reducing pain from damage to the nervous system itself than the opiate-dependent system, but this is sometimes the converse. While cross tolerance to morphine from electrical stimulation of the endogenous opiate system exists in animals, it does not seem to be a problem clinically as the abstinence syndrome and tolerance have not been a problem in humans. PMID- 2225094 TI - Effects of opioid peptides on peripheral stimulation and "stress"-induced analgesia in animals. AB - This review has established the basis for an opiate pain-inhibitory system as well as pharmacological and physiological evidence suggesting alternative nonopiate systems. The concept of multiple forms of pain inhibition became apparent through the study of stress-induced analgesia and the classification of effects across opioid/nonopioid and neural/neurohormonal dimensions. These effects were compared with traditional pathways identified for opiate pain inhibition, and the use of other environmental forms of analgesia (cervical probing, defeat) were explored similarly. To conceptualize how these multiple analgesic systems might interact, a collateral inhibition model was described for opioid and nonopioid systems, while a synergy model examined two responses from the same class. The existence and further characterization of these multiple systems have obvious clinical and therapeutic importance, and systematic approaches to the mechanisms involved have been identified for further empirical investigation. PMID- 2225095 TI - Cerebral vasospasm. AB - Cerebral vasospasm (specifically, intracranial arterial spasm) is variously defined as: (1) an arteriographically evident narrowing of the lumen of one or more of the major intracranial arteries at the base of the brain due to contraction of the smooth muscle within the arterial wall, or due to the morphological changes in the arterial wall and along its endothelial surface that occur in response to vessel injury; (2) the delayed onset of a neurological deficit following subarachnoid hemorrhage, thought to be due to ischemia or infarction of a portion of the brain; or (3) the combination of these two features (symptomatic vasospasm). The arterial contraction of intracranial arterial spasm typically develops a few days after the rupture of an intracranial aneurysm and lasts 2 to 3 weeks. Such arterial spasm can also occur in other conditions such as head trauma. If it is severe enough it can lead to cerebral infarction. The pathogenesis of this condition is still unclear. Many ingenious attempts have been made to prevent or treat cerebral vasospasm, but most have failed. The best current approach is to ensure adequate blood volume, and to elevate the patient's blood pressure (especially if the aneurysm has been secured by an early operation). The continuing investigation of drugs such as calcium channel blocking agents to improve the cerebral circulation has begun to provide additional help. PMID- 2225096 TI - [Determination of gestational age by ultrasound]. AB - The authors elaborated a procedure for correction of the gestation age by ultrasonic examination in pregnant women in the second and third trimester of gestation. The method was tested in a group of 500 pregnant women who were examined within the framework of a special ultrasound screening. In 5% of the group the gestation age calculated according to the last menstrual bleeding was not consistent with the results of the ultrasound examination. In these instances a correction was made in case the difference between the ultrasonic finding and the gestation age according to menstruation was two weeks or more, in the first as well as second trimester. In these instances the correction was made with regard to the difference in the first trimester. In the group of women where the correction was made there was in 44% a case-history of irregular menstrual cycles, as compared with 13% in the group where the ultrasonic finding was consistent with the gestation age according to the date of menstruation. In the majority of women (73%) with a shift of the conceiving ovulation the difference of the ultrasonic finding, as compared with the gestation age according to the last menstruation was three weeks or more. PMID- 2225097 TI - [The effect of chronic exposure to lead on lysosomal levels in amniotic fluid in an experimental model]. AB - Groups of female rats were exposed for prolonged periods to different lead concentrations in drinking water; in one group was also added to the drinking water, in the amniotic fluid of exposed females greatly reduced lysozyme values were found, as compared with controls. Concurrent Zn administration considerably reduced the effect of lead. Long-term exposure to low concentrations of lead caused a greater drop of lysozyme levels in amniotic fluid than that found in previous experiments after short-term exposure to higher lead concentration. PMID- 2225098 TI - [Clinical problems in postpartum psychoses]. AB - The authors analyzed post-partum psychoses treated at the Psychiatric Clinic of the Faculty Hospital in 1985-1986. The group comprised 41 patients. Post-partum psychoses are not considered a separate nosological unit nor symptomatic mental disorders but are classified as endogenous psychoses, provoked by childbirth. As to endogenous psychoses, most frequently manic depression is involved, as suggested by the clinical picture and course. Schizophrenia is found less frequently, as compared with manic depression, the cca 1:10. In rare instances post-partum symptomatic psychosis may develop. PMID- 2225099 TI - [Fertility in gonadal dysgenesis]. AB - At the Second Gynaecological and Obstetric Clinic in Prague there are at present 78 phenotypic women with dysgenetic gonads in dispensary care. In 61.5% the main reason for examination in a specialized department was infertility. Based on a comprehensive examination, the authors demonstrate the relationship between chromosomal complement and histology of the gonads on one side and fertility on the other. 31% of women with dysgenetic sclerocystic gonads became pregnant after surgical and hormonal treatment. In 27% of the dispensarized group genital and extragenital tumours were detected. PMID- 2225100 TI - [The first 10 pregnancies in the in vitro fertilization and embryo transfer program of the Institute for Maternal and Child Care using transvaginal follicular puncture]. PMID- 2225101 TI - [Changes in cholinergic innervation of the fallopian tube in women during the menstrual cycle]. PMID- 2225102 TI - [Initial experience with early amniocentesis]. PMID- 2225103 TI - [SP1 levels in maternal serum in the second half of pregnancy with a genetically stigmatized fetus]. PMID- 2225104 TI - [Childbirth in women in the care of a single obstetrician]. PMID- 2225105 TI - [Negative HCG in extrauterine pregnancy]. PMID- 2225106 TI - [The Wissler-Fanconi syndrome after hysterectomy]. PMID- 2225107 TI - [Aphrodisiacs in gynecology]. PMID- 2225108 TI - [Developmental morphology of the human corpus luteum]. PMID- 2225109 TI - [History of the cesarean section]. PMID- 2225110 TI - [Comments on the work of L. Barnet et.al. "Our experience with monitoring drug prescriptions in pregnancy"]. PMID- 2225111 TI - [Trends in the frequency of cesarean section and its indications in Czechoslovakia]. PMID- 2225112 TI - [Regional differences in the number of abortions on demand in the Czech Republic]. PMID- 2225115 TI - [Contraception and risk factors for the development of diseases of the uterine cervix]. AB - In a group of 350 women operated on account of diseases of the uterine cervix in 1986-1988 risk factors associated with cancerogenesis were evaluated. The author provided evidence of a significant rise of CIN in conjunction with contraception. The rise of number of CIN cannot be differentiated from social factors and sexual behaviour of women which are directly related to the increased risk of cancer of the uterine cervix. PMID- 2225114 TI - [Morphologic basis of hemorrhage during hormonal therapy in the climacteric syndrome]. AB - In a group of 133 postmenopausal women in the course of nine years the relationship between two types of hormonal treatment and one of the side-effects- metrorrhagia--was investigated. This symptom was found in 37 patients. The authors followed two aims. To evaluate the relationship between treatment of the climacteric syndrome and the morphological state of the uterine mucosa and to assess the optimal therapeutic pattern under local conditions. The insignificant frequency of proliferating endometrial changes supports some data in the literature which draw attention also to other causes of haemorrhage. With regard to therapeutic regimes, the authors consider continual administration of conjugated oestrogens--0.625 mg and medroxyprogesterone acetate 5 mg per day as suitable. They emphasize the necessity to follow up the patients in a special clinic with the opportunity to make hormonal examinations and to ensure interdisciplinary collaboration. PMID- 2225113 TI - [Spontaneous and induced fetal movement activity in the 2d trimester of pregnancy]. AB - During routine screening in the first half of pregnancy the authors evaluated in 3446 foetuses the incidence of spontaneous movements and movements after their attempted induction by movement of the uterus, when no spontaneous movements were recorded during examination. The examinations were made by means of a rotation probe 3.5 MHz of a Sonoline 2 apparatus (Siemens) always between 7.30 and 11.30 a.m. It was revealed that: 1. Spontaneous motor activity of the foetus depends significantly ot the foetal age; during the period between the 12th and 16th week it was recorded in 94.4%, in the 17th to 21st week it declines to 87.4% and during the 22nd-25th week it rises again to 94.7%. 2. The number of foetuses where movements were recorded after the first movement of the uterus depends also significantly on foetal age: in the 12th-16th week it is 57.5% of the number of foetuses without spontaneous movement, in the 17th to 21st week 66.3% and in the 22nd to 25th week 66.7%. 3. On the basis of preliminary work it is not possible to decide whether the movements observed after movement of the uterus are spontaneous or induced, however, if attempts to induce movements would imply only prolonged examination and recording of spontaneous activity, it is justified. 4. In one foetus where we did not observe spontaneous activity nor movements after movement of the uterus we revealed during a check-up examination rapidly developing polycystic kidneys. 5. Observation of foetal movements during screening is not time consuming and should become a matter of routine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225116 TI - [Endomitoses and squamous pearls in cervix dysplasia]. AB - The authors describe the cytological and histological picture of intraplasmic inclusions in dysplasias of the cervix, apparent under the microscope. Their development may be due to cellular cannibalism or incomplete cell separation after abnormal nuclear division. The latter mode of cell division is probably associated with the development of squamous pearls observed in advanced dysplasias. Squamous pearls in cervical dysplasias do not attain the dimensions and degree of keratinization as pearls in squamous carcinoma, their similarity is, however, striking. PMID- 2225117 TI - [Clinical study of morbidity in children in relation to the method of guiding the 2d stage of labor]. PMID- 2225118 TI - [Therapy of mycotic colpitis with terconazole (Gyno-Terazol)]. PMID- 2225120 TI - [The occurrence of Chlamydia, Mycoplasma and Ureaplasma in sterile married couples]. PMID- 2225119 TI - [Personal experience with SolcoTrichovac]. PMID- 2225121 TI - [Screening for endometrial carcinoma using our special aspiration cannula]. PMID- 2225122 TI - [Concurrent acute leukemia and pregnancy]. PMID- 2225123 TI - [Combination of intrauterine and extrauterine pregnancy]. PMID- 2225124 TI - [Giant subserous pendulous liquefied uterine myoma]. PMID- 2225126 TI - [Methods of assisted reproduction]. PMID- 2225125 TI - [Current opinion on the pathogenesis of prolonged pregnancy]. PMID- 2225127 TI - [Barrier contraception increases the risk of pre-eclampsia]. PMID- 2225128 TI - [Obstetrical surgery at the Brno Clinic during the 1st Czechoslovak Republic]. PMID- 2225129 TI - [Problems in artificial insemination and the activity of sperm banks]. PMID- 2225130 TI - [Screening for precancerous conditions and preclinical carcinoma of the uterine cervix in the Western Bohemian Region]. PMID- 2225131 TI - [100 years since the birth of Vilem Laufberger]. PMID- 2225132 TI - [V. Laufberger on metamorphosis in the axolotl]. PMID- 2225133 TI - [Physiological aspects of electrical fields of the heart]. PMID- 2225134 TI - [Development of modern electrocardiography--100th anniversary of the birth of Academician Vilem Laufberger]. PMID- 2225135 TI - [Electrocardiology problems in orthotopic heart transplantation]. PMID- 2225136 TI - [From the breaking up of cells to molecular physiology]. PMID- 2225137 TI - [Transferrin, transferrin receptors and incorporation of iron into cells]. PMID- 2225138 TI - [Laufberger's "excitation theory" today]. PMID- 2225139 TI - [Laufberger's Practical Physiology (1946)]. PMID- 2225140 TI - [A remembrance of academician Vilem Laufberger]. PMID- 2225141 TI - [A list of the works of Academician V. Laufberger 1975-1984 (part 3)]. PMID- 2225142 TI - The RAD50 gene, a member of the double strand break repair epistasis group, is not required for spontaneous mitotic recombination in yeast. AB - Mutations in the RAD50 gene of Saccharomyces cerevisiae have been shown to reduce double strand break repair, meiotic recombination, and radiation-inducible mitotic recombination. Several different point mutations (including ochre and amber alleles) have been previously examined for effects on spontaneous mitotic recombination and did not reduce the frequency of recombination. Instead, the rad50 mutations conferred a moderate hyper-rec phenotype. This paper examines a deletion/interruption allele of RAD50 that removes 998 of 1312 amino acids and adds 1.1 kb of foreign DNA. The results clearly indicate that spontaneous mitotic recombination can occur in the absence of RAD50; in fact, the frequency of recombination is elevated over the wild-type cell. One possible interpretation of these observations is that the initiating lesion in spontaneous recombination events in mitosis might not be a double strand break. PMID- 2225143 TI - The mitochondrial nad5 gene of sugar beet (Beta vulgaris) encoding a subunit of the respiratory NADH dehydrogenase. AB - We have isolated the nad5 gene from the N-cytoplasm of Beta vulgaris, by heterologous hybridization with a nad5 probe from Chlamydomonas reinhardtii, and have determined the DNA sequence. The gene has a length of 3082 bp and consists of three exons and two introns, 459, 1269, 270, 848 and 357 bp in length, respectively. It has a similarity of 95.1% at the DNA level to the nad5 gene of Oenothera and the two respective proteins show an overall level of amino acid identity of 88.7%. Compared to Oenothera the reading frame of the first exon is extended in the 5' direction and in the third exon there is a frameshift shortening the reading frame by 96 bp and changing the last 48 codons. The nad5 gene is a single copy gene in the N- and S-cytoplasm of Beta vulgaris and the organisation of the gene shows no apparent differences in the two cytoplasms. The gene is actively expressed; three major transcripts are detectable. The transcript patterns have been compared between the two cytoplasms and between different plant tissues. PMID- 2225144 TI - Translational accuracy and sexual differentiation in Chlamydomonas reinhardtii. AB - A renewal of ribosomes has been previously reported to occur during gametogenesis in C. reinhardtii. In order to further characterize these new ribosomes, we performed pulse-labelling experiments on whole cells of C. reinhardtii, during gametogenesis and in the presence of various aminoglycosides known to alter translational accuracy: Hygromycin and Paromomycin are assumed to increase the rate of translational errors at the level of 80S and 70S ribosomes whereas Kasugamycin is assumed to induce the opposite effect. Three lines of evidence support an increased inaccuracy in protein translation during gametogenesis: (1) gamete cells displayed a higher sensitivity than vegetative cells to Hygromycin and Paromomycin; 4 micrograms/ml Hygromycin cancelled cytoplasmic protein synthesis in gametes but not in vegetative cells; Paromomycin induced the synthesis of new polypeptides of high molecular weight and of nuclear origin in gametes but not in vegetative cells. In addition, chloroplast protein synthesis was more sensitive to Hygromycin and Paromomycin in gametes than in vegetative cells. (2) Kasugamycin-sensitive alterations of thylakoid membranes were detected during gametogenesis. (3) 35S-misincorporation in the OEE3 polypeptide, of nuclear origin and normally devoid of sulphur containing amino acids, was more than three times higher in gametes than in vegetative cells. This increase was prevented by Kasugamycin, suggesting that 80S translation in gametes was more inaccurate than in vegetative cells. The possible significance of these changes occurring during gametogenic differentiation is discussed in light of the importance of a modulation of translational accuracy at particular stages of the life cycle in other lower eukaryotes. PMID- 2225145 TI - Cloning and expression of a second Aspergillus niger pectin lyase gene (pelA): indications of a pectin lyase gene family in A. niger. AB - Using the previously cloned Aspergillus niger N756 pectin lyase D gene as a probe, the corresponding pelD gene has been isolated from a genomic library of the laboratory strain A. niger N400. This gene encodes PLD, previously described as PLI, which is one of the two major pectin lyases isolated from the commercial pectinase preparation Ultrazym. Heterologous hybridization of the A. niger N400 genomic library with the pelD gene led to the isolation of another five genes: pelA, B, C, E, and F. These genes differ in their hybridization patterns with probes containing either the entire pelD gene, or 5' or 3' parts thereof. By partial sequencing, and expression in an A. niger transformant containing multiple copies of the pelA gene, we show that this gene, which hybridizes strongest with the pelD gene, encodes the other major pectin lyase from Ultrazym, PLII. PMID- 2225147 TI - [Clinico-genetic problems in retinoblastoma. Retinoblastoma and heredity (review)]. PMID- 2225146 TI - The influence of GAP promoter variants on hirudin production, average plasmid copy number and cell growth in Saccharomyces cerevisiae. AB - The yeast Saccharomyces cerevisiae has been engineered to synthesize and secrete desulfato-hirudin (hirudin), a thrombin inhibitor from the leech Hirudo medicinalis. The synthetic gene coding for hirudin was expressed constitutively under the control of four size-variants of the yeast glyceraldehyde-3-phosphate dehydrogenase promoter (GAP) and cloned into a 2 mu based multicopy yeast vector. The constitutive action of the four promoter variants was confirmed by demonstrating that the expression and secretion of hirudin is growth-related. The different efficiencies of the promoter variants not only affected hirudin expression but also led to changes in several cellular parameters, such as cell growth, average plasmid copy number and plasmid stability. The observed changes show that yeast cells establish a specific equilibrium for each promoter variant. We conclude, that the adjustment of cellular parameters in response to the expression levels of a heterologous protein is regulated by two counteracting selective forces: (1) the need for complementation of the auxotrophic host marker by the plasmid-encoded selection gene which, in the case of dLEU2, requires several plasmid copies; and (2) a selective advantage of cells with a lower copy number enabling them to escape the burden of heterologous protein production. PMID- 2225148 TI - [Clinical analysis of 35 patients with retinoblastoma followed-up for 25 years]. AB - The author presents a comprehensive analysis of a group of 35 patients with retinoblastoma followed up for 20 years at the Ophthalmological Clinic of the Faculty Hospital in Bratislava, focused on the aetiology, diagnosis, treatment and prognosis of the disease. Special emphasis is laid on the investigation of indicators which differentiate hereditary and non-hereditary retinoblastoma and on the application of these indicators for the evaluation of the clinical picture and for genetic consultations. PMID- 2225149 TI - [Surgery in sequelae of chemical and thermal burns of the eye]. AB - The treatment of sequelae of chemical and thermal burns of the eye is sometimes very difficult. Previous to a event, keratoplasty all symblephara have to be removed. If there is no conjunctiva, transplantation from the second eye or from a donor is necessary. A method of transplantation of donor conjunctiva with a corneal lamella has been worked out as preparation for keratoplasty. Epithelium than can migrate to the transplant. In quantitative or qualitative alterations of the tears, the condition can be improved by soft contact lenses. In about one third of serious burns longtermed good results can be gained. PMID- 2225150 TI - [Prostanoids and leukotrienes in ophthalmology. I. Basic biochemistry and physiology of prostanoids and leukotrienes]. AB - The authors give a brief account of hitherto assembled knowledge on the biochemistry and physiology of prostanoids and leucotrienes. They describe the history of investigations of these substances, their properties and patterns of synthesis. The authors evaluate possibilities of the pharmacotherapeutic use of inhibitors of prostanoid and leucotriene synthesis. PMID- 2225151 TI - [Prostanoids and leukotrienes in ophthalmology. II. Role of prostanoids and leukotrienes in the physiology and pathophysiology of the eye]. AB - The authors give an account on the development and contemporary knowledge regarding the participation of prostanoids and leukotrienes in physiological and pathophysiological processes of the eye. According to many data in the literature of all intraocular tissues of the human eye the greatest prostaglandin production was found in the anterior segment of the choroid. The authors describe the role played by these substances in the pathogenesis of inflammations, their importance in the regulation of intraocular pressure and in the development of cystoid macular oedema. PMID- 2225152 TI - [Prostanoids and leukotrienes in ophthalmology. III. Results of a clinical study of local administration of indomethacin in preoperative and postoperative care]. AB - The authors submit results of the clinical investigation involving indomethacin administration during preoperative and postoperative care of patients with primary glaucoma who were submitted to trabeculectomy. The investigation was made by the method of a double blind trial. Indomethacin 0.5% eye drops or placebo were administered on the day prior to operation to the 10th day after operation, three times a day. During the final comparison of the two groups after indomethacin a reduction of the number of postoperative complications was observed, as well as a shorter hospitalization period, and the result of the filtering operation was not affected. PMID- 2225153 TI - [Risk factors for diabetic retinopathy in children and adolescents with type I diabetes mellitus]. AB - Based on repeated fluoroangiographic examinations in a group of 28 children with type I diabetes mellitus the authors observed progressing diabetic retinal changes. At the end of the three-year observation period they found progress in 32% of the children. They investigated influence of risk factors such as age, duration of the basic disease, its metabolic compensation, sex and HLA typing on the development of diabetic retinopathy. PMID- 2225154 TI - [Microsurgery knives with crystalline blades]. AB - In collaboration with the national enterprise Monokrystaly Turnov and the workshops of the Medical Faculty, Charles University, Hradec Kralove the authors designed and produced microsurgical knives with an exchangeable inserted blade made from leucosapphire. They describe their experience with the manufacture and clinical use of these new local instruments. PMID- 2225155 TI - [Use of soft contact lenses in the treatment of corneal erosions]. AB - The author gives an account of favourable experience with gel contact lenses, produced locally, in the treatment of traumatic corneal erosions. Patients treated by means of therapeutic contact lenses recovered more rapidly (by 1.2 days, as compared with a control group treated by covering the eye). The great advantage of the contact lens method is that the patients could use the injured eye during treatment. In some instances even work incapacity was not necessary. Contact lenses can be resterilized and the cost of treatment is relatively small. Daily check-ups are, however, necessary and contact lenses should be inserted by an experienced ophthalmologist. PMID- 2225157 TI - [Information on Fresnel prisms and hyperopic spectacles]. PMID- 2225156 TI - [The research work of Dr. Jiri Franta in the shadow of his death sentence]. AB - A report on three manuscripts written in German by Doc. Dr. J. Franta (1899-1945) in prison after his death verdict (May 7, 1943) for his activity in the resistance movement. The first manuscript--a contribution on the genesis and medicamentous treatment of cataract--was a conspectus (16 pp.). After a positive review by prof. Dr. H. Rieger it served as the basis for five chapters which formed the second manuscript (52 pp.). The working hypothesis on the influence of infrared radiation on the intraocular metabolism and the suggested detailed local and general, clinical and experimental examination of subjects with a transparent and opaque lens was important. In the third manuscript (12 pp.) the author outlined his plan of biochemical examinations in keratoplastic operations, in particular as regards material from donors. Even after reading Franta's letters from prison addressed to his family, the circumstances under which the manuscripts were written are not quite clear--permission to do research given to a person sentenced to death is quite exceptional. PMID- 2225159 TI - [Personal experience with adjuvant chemotherapy of malignant tumors in otorhinolaryngology]. AB - The authors give an account on the therapeutic results of adjuvant polychemotherapy in advanced squamous-cell carcinomas in the ENT region. Based on their conclusions they recommend in these malignities (stage III, IV) comprehensive treatment comprising neo-adjuvant polychemotherapy, surgery supplemented by simultaneous radiopolychemotherapy along with cyclic adjuvant chemotherapy and hyperthermia. PMID- 2225158 TI - [Personal experience with antibiotic prophylaxis in extensive otorhinolaryngologic procedures]. AB - The authors compare the effectiveness of three types of antibiotic prophylaxis (1. cephazoline, 2. combination ampicillin + oxacillin, 3. clindamycin) in a group of 32 patients with resection of oropharyngeal carcinomas and in a group of 47 laryngectomies with cervical block resection. The criterium is the incidence of postoperative infections, which called for a change of antibiotic treatment. The authors evaluates favourably prophylaxis with cephazoline and clindamycin; the incidence of complications is within the range of 17-30%. In ampicillin + oxacillin therapy unsatisfactory results with a 46% incidence of inflammatory complications were recorded. A gram-negative flora causes 45% infectious complications; the author also draws attention to the danger of anaerobic infections. In a primarily contaminated oropharyngeal area there is an incidence of postoperative infections by 30% higher in all types of evaluated prophylaxis, as compared with the laryngocervical area. PMID- 2225160 TI - [Surgical treatment of patients with carcinoma of the larynx at the Otorhinolaryngology Clinic in Martin]. AB - In 1973-1985 at the ENT Clinic of the Faculty Hospital with policlinic in Martin 559 patients with carcinoma of the larynx were treated: 23 women and 529 men. Thirteen women and 286 men were operated. Partial resection was performed in 137 patients. The best results were recorded after chordectomy, the poorest results after horizontal partial resection of the larynx. The author discusses the effectiveness of laryngectomy after previous partial surgical operation of the larynx, early diagnosis and corrected indication for surgical operation. PMID- 2225161 TI - [Present trends in endoscopy in otorhinolaryngology]. AB - The author emphasizes new endoscopic trends in otorhinolaryngology, in particular rhinoscopy with microsurgery of the lateral nasal wall, sinuscopy and the use of lasers in microlaryngoscopy. Attention is also drawn to the specific position of endoscopy in otorhinolaryngology, using not only flexible and rigid technique but also possibilities of concurrent examination of the respiratory and deglutition pathways--i. e. so-called double endoscopy. The possibility of a comprehensive endoscopic examination of the deglutition and respiratory pathways led also to the formulation of the principle of panendoscopy the importance of which for oncological diagnosis is already generally accepted. PMID- 2225162 TI - [Importance of laryngomicroscopy and fibrolaryngostroboscopy in the early diagnosis and surgical treatment of laryngeal cancer]. PMID- 2225163 TI - [Rhinogenous phlegmons of the orbit]. AB - During the past 15 years we treated at the ENT department and ophthalmological department of the hospital with policlinic type III in Nitra 10 patients with orbital phlegmons or an abscess of the eyelid after an eye injury treated and cured by antibiotic treatment and external drainage. Twelve patients had a rhinogenic phlegmon or abscess in the orbit (one patient had a dentogenic aetiology of the inflammation). This group of 12 patients were treated in addition to antibiotics in different combinations also surgically (in one case also by drainage of the abscess from a lateral quadrant of the orbit). In five instances the authors found in addition to the phlegmon of the periorbital tissue also an abscess in the depth of the orbit and six times an abscess of the eyelid. Despite the radical approach to the inflammation of the paranasal sinuses and inflammation of the orbit, two patients developed blindness of the damaged eye and one patient died from rhinogenic suppurative meningitis. PMID- 2225164 TI - [The significance of the supratubal recess in the surgical treatment of chronic otitis]. AB - The processus supratubalis is a complicated space from the topographical aspect. The author emphasizes the need of careful peroperative examination of the area which may be the site of a residual cholesteatoma. The pathological process at this site may, due to topographic relations with important structures, cause serious functional disorders. PMID- 2225165 TI - [Saturation of middle ear reflexes in occupational hearing loss]. AB - In the ENT department of the Factory Institute of National Health of the uranium industry in Pribram a group of 196 men (392 ears) was examined who worked exposed to the risk of noise in different occupations, mostly as miners in the uranium mines. The noise exposure was 17.5 +/- 6.5 years, age 60.2 +/- 11.7 years, the total percentage hearing loss (calculated according to Fowler) 54.7 +/- 21.1%. The group was formed by 144 men who were examined during a preventive follow-up examination, 52 men where hypacusia was evaluated as an occupational disease. The examination of all patients was supplemented by a record of middle-ear reflexes induced by contralateral stimulation at frequencies of 0.5 kHz, 1 kHz, 2 kHz and 4 kHz and by white noise (WN). The regression equation y = 50.54-0.044X (y = percentage hearing loss per ear, x = noise exposure in years) was calculated from data of the group subjected to the preventive follow up examination and made it possible to divide the group into sub-groups, sensitive and resistant to noise. The group of occupational hypacusia comprised only sensitive subjects. The authors tested the frequency and thresholds of middle ear reflexes at different frequencies and WN, the frequency and thresholds of saturation of reflexes separately in groups sensitive and resistant to noise. It was not possible to draw conclusions from the results which would permit a forecast of the individual development of occupational hypacusia as regards early evaluation of sensitivity or resistance to noise. PMID- 2225166 TI - [Etiology of congenital hearing disorders in children]. AB - The author analyzes factors which may play a part in the aetiology of severe congenital bilateral perception deafness--practically complete deafness--in children. The group of patients comprises 177 deaf children, 135 siblings with normal hearing and 70 deaf parents and other relatives. Pathological factors during pregnancy were detected in 20, perinatal and neonatal pathology in 32 instances. If the anamnestically detected risk factors in the aetiology of the hearing deficit played a part, theoretically by their elimination a considerable proportion of the congenital hearing affections in children could be prevented. The author emphasizes the necessity of collaboration with a geneticist in the prevention of inborn hereditary deafness. PMID- 2225167 TI - [Spatial positional orientation in deaf-mute individuals with bilateral vestibular areflexia]. AB - Ten deaf-mute subjects with total vestibular areflexia were subjected to positional tests, i.e. assessment of the postural subjective vertical and horizontal plane by deviations in the frontal and sagittal plane. The tests were performed in the author's modification of a Grahe table. Comparison with the results of 10 healthy subjects revealed that extinction of vestibular activity increases the inaccuracy of assessment of the body position in space. The conclusion is: the vestibular (otolith) apparatus supplements and makes the activity of all other gravireceptors more accurate but not hold a dominant place among them. PMID- 2225168 TI - [Personal experience with sialography]. AB - The author emphasizes the importance of sialography in the diagnosis of diseases of the salivary glands. By using an intravenous polyethylene cannula it is possible to combine functional examination of the salivary glands (sialometry and sialochemistry) with X-ray examination after filling the glands with contrast substance. In a group of 34 patients sialography contributed to a correct diagnosis in 26 patients, i.e. 76.5%. False positive results were recorded in 1 case (2.9%), false negative results in three (8.8%). From a total of eight tumours of the salivary glands the examination in two cases (25%) did not lead to a correct diagnosis. In 16 instances (47%) the conclusion of the sialographic examination was compared with results of the histological and cytological examination. PMID- 2225169 TI - [Hemangiomas of the larynx in children--results of surgical treatment]. AB - Surgical treatment of six cases of haemangiomas of the larynx. Surgery was used only after all conservative means were exhausted. After complete removal of the tumour after a two-year interval no relapse was recorded. The function of the larynx was not impaired. PMID- 2225171 TI - [An unusual early complication of tonsillectomy]. AB - The authors describe the observation of a localized tissue emphysema of the right cheek, which developed in an eight-year-old child as the early complication of tonsillectomy performed under local anaesthesia. In addition to reflections on the possible pathways of the gas from the tonsillar bed into interstitial spaces of the cheek, the authors draw attention also to possible concurrent penetration into the soft tissues of the neck and mediastinum. PMID- 2225170 TI - [Iatrogenic injuries of the facial nerve in the mastoid region]. AB - During the past ten years nine patients were referred to our hospital with lesions of the VIIth nerve. These lesions were inflicted during operation on account of chronic otitis media. One patient recovered after conservative treatment. Based on the EMG examination and clinical picture, eight patients were operated. In one who had an extensive lesion it did not prove possible to find the proximal stump and the patient improved after Normann-Dott's operation. In the remaining seven subjects also severe damage was involved: five times complete severing of the nerve occurred, twice partial severing and contusion, always in the mastoid portion of the VIIth nerve. The authors achieved as a rule a 50-75% restoration of function of the VIIth nerve Ballance-Duel's operation, using a graft of the n. suralis with microsuture of the epineurium and gluing of the nerve by plasma. Evaluation of late functional results was made 1-8 years after Ballance-Duel's operation. The authors recommend to reduce the risk of iatrogenic lesions of the VIIth nerve in beginners by assistance of experienced surgeons at several operations. PMID- 2225172 TI - [Malignant neurofibroma of the cervical portion of the vagus nerve]. AB - The authors give an account of a malignant neurofibroma of the cervical portion of the vagus in Recklinghausen's disease in a 29 year-old man. The tumour was removed with part of the nerve. Relatively shortly after operation a local relapse of the tumour developed, with propagation into the posterior cranial fossa, which proved fatal. The authors discuss diagnostic difficulties, possibilities of treatment and the prognosis of malignant neurogenic tumours. PMID- 2225173 TI - [Diabetic neuropathy. Diagnosis and classification]. PMID- 2225174 TI - "Pseudodementia" and "pseudodepression": a short review on the coexistence of cognitive and affective impairment in the elderly. PMID- 2225175 TI - [Psychological aspects of pain]. PMID- 2225176 TI - [Vascular epilepsy]. PMID- 2225177 TI - [Cerebral circulation using transcranial and extracranial doppler ultrasonography in a patient with vertigo and ischemia in the area of the brain stem]. AB - The authors examined 32 patients with vertigo, 17 patients with focal ischaemia of the brain stem and 24 patients without signs of affections of the central nervous system by transcranial and extracranial Doppler ultrasonography. They measured the flow velocity in the basilar artery (BA), in the intracranial portion of the vertebral artery (VA) and in the extracranial portion of the internal carotid artery (ICA). In patients with vertigo they investigated functional and organic changes in the area of the cervical spine. They found significant differences in the flow velocities between groups as well as in different indices calculated from the assessed values. The lowest flow velocities were recorded in patients with focal ischaemia of the brain stem. The authors evaluate the influence of haemodynamics and disease of the cervical spine on the development of vertigo. PMID- 2225178 TI - [Trigeminal evoked potentials. Normal values]. AB - The author describes the examination technique of trigeminal evoked potential (TEP) by electric stimulation with paired skin electrodes separately for each side of the maxillary and mandibular branch of the trigeminal nerve. The obtained evoked response contains two negative and two positive deflections N11, P19, N27, P39, whereby wave P39 could not be evaluated in 47.8%; therefore it was not processed by statistical method. The other latency values are stable against a major variability of amplitudes. Evaluation by linear regression displayed only a minor correlation of latencies of the trigeminal evoked potential with advancing age. The author present normal latency and amplitude values for every side of maxillary and mandibular part of the Vth nerve as well as maximal lateral differences. With regard to the hypothetical possibility to influence results of the trigeminal potential by afferentiations of the VIIth nerve in patients with idiopathic paresis of the fascial nerve, this method in not a suitable model for testing the selectivity of examinations of TEP. The submitted method of trigeminal evoked potential is reliable and simple and can be used as a diagnostic aid in examinations of the functional state of the pathway of the Vth nerve, e.g. in multiple sclerosis, neuralgia of the Vth nerve, tumours of the Vth nerve and in conditions after operation of the Vth nerve. PMID- 2225179 TI - Electrophysiological characterization of central sensory and motor pathway function in patients with moderate hemiparesis. I. Methodical approach. AB - The central sensory and motor pathway function in healthy persons and patients with several neurological disorders was selectively characterized by evaluation of latencies of short (R1) and long (R2) latency EMG responses as well as simultaneously recorded somatosensory potentials (N19, N26) evoked by electrical stimulation of N.medianus and N.peroneus. On the basis of these latencies the peripheral and central sensory/motor conduction times were calculated. By using this investigation procedure a selective quantification of central pathway functions is possible. PMID- 2225181 TI - [Laryngeal voice production: neurological aspects. Possibilities of laryngeal voice production analysis]. PMID- 2225180 TI - Electrophysiological characterization of central sensory and motor pathway function in patients with moderate hemiparesis. II. Clinical results. AB - The central sensory and motor pathway function in patients with moderate hemiparesis and in healthy persons was selectively characterized by evaluation of latencies of short (R1) and long (R2) latency EMG responses as well as simultaneously recorded sensorimotor potentials (N19, N26) evoked by electrical stimulation of median and peroneal nerve (additionally, calculation of peripheral and central sensory/motor conduction times). This investigation procedure permits a noninvasive quantification of disturbed central sensory and motor pathway function in hemiparetic patients. The results found are in agreement to clinical, CT and other examination findings. PMID- 2225182 TI - [The basilar artery terminal branch syndrome. Paramedian meso-thalamic infarct]. AB - The author describes two cases of paramedian mesothalamic infarction as part of multiple infarctions in occlusions of the top of the basilar and peduncular segment of the posterior cerebral artery. Based on published work and the author's own observations, the clinical syndrome of this infarction was defined and comprises five symptoms: impaired consciousness, amnestic syndrome and paralysis of vertical views due damage of formations in the area of paramedian thalamo-subthalamic (thalamoperforate) arteries by neuropsychic abnormalities and contralateral hemidefects due to damage of structures in the neighbouring thalamic and parathalamic areas. PMID- 2225183 TI - [Spectrophotometry of native cerebrospinal fluid: artificial "bilirubin" xanthochromia]. PMID- 2225185 TI - [Initial experience with elements of the clinical psychology information system]. AB - The authors report on their initial experience with the evaluation of standard records of psychological examinations in a mental asylum. These evaluations are limited by the assembled indicators, but despite these limitations they help to give an idea on the usefulness of psychological examinations. The author discusses also other possibilities how to develop the clinical psychological information system. PMID- 2225186 TI - [Jellinek's developmental stages and their reality under our sociocultural conditions]. AB - In a group of 250 hospitalized male patients with the diagnosis 303 the author tested the aptness of Jellinek's developmental stages of alcoholism which are widely used in Czechoslovak alcohology. It was demonstrated that the developmental stages are not integrated developmental stages, that they lack the necessary compactness in the chronological sequence and in the frequency of individual phenomena. Loss of control (8) in the reported form is closer to the onset of development and the frequency of palimpsests (7) develops later, usually is overlaps with prolonged drunkedness (31). At the onset of development dominates "non-adaptive" drinking evaluated frequently as loss of control and in the more advanced stage the constant incidence of palimpsests causes frequent intoxication and declining tolerance. Among individual phenomena the following are important: in stage I regular contact with the drug (04) and increased tolerance (05), in stage II secret drinking (2) and frequency of palimpsests (7), in stage III signs derived mostly from rationalization and alcohol-centered behaviour and finally in stage IV impaired thinking (33), reduced tolerance (37) and possible ethic degradation (32). As to different developmental stages the chronic stage sounds most convincing. PMID- 2225184 TI - [Results of treatment of schizophrenic and schizoaffective patients with sulpiride (Eglonyl Alkaloid) in comparison with perphenazine (Perfenazin Spofa)]. AB - In a three-week crossover controlled the authors administered alternately sulpiride and perphenazine with an intermittent placebo interval, to 40 hospitalized patients with acute exacerbation of schizophrenic and schizoaffective psychosis. According to evaluation recommended by Serejsky significantly more complete remissions type AB were achieved especially in schizodepressive patients given sulpiride. The global score of BPRS and FKP scales after administration of the two tested neuroleptic drugs differed: sulpiride had a more favourable effect on depression, emotional withdrawal, reduced affectivity, slower motor activity, worry about the somatic state and hallucinations, while perphenazine gave better results in patients with reduced compliance, lack of cooperation, hostility and excitation. Sulpiride is well tolerated by the patients. Pharmacological parkinsonoid was observed only in cca half the patients, as compared with perphenazine and therefore also the need of correction by antiparkinsonian drugs was significantly smalled. The low incidence of extrapyramidal, hypnosedative and autonomous undesirable effects gave sulpiride the optimal position in our classification of 16 tested neuroleptic drugs. In one third of the patients no undesirable side--effects were observed. PMID- 2225187 TI - [Sulpiride (Eglonyl Alkaloid) in the treatment of functional disorders of the digestive tract]. AB - Sulpirid was administered in an open clinical trial--150 mg/day for 4 weeks--to 31 patients (15 man and 16 women, mean age 31.5 years, mean duration of complaints 1 month to 6 years) suffering from functional disorders of the digestive system. Their health status was evaluated by a specialist in internal medicine, by a psychiatrist and a self-administered SCL-90 questionnaire before the onset of treatment and after four weeks. In 29 patients the complaints disappeared or improved markedly and this improvement persisted also after discontinuation of the drugs. In the entire group a significant drop of the mean initial intensity of psychopathological feature in all dimensions of the questionnaire occurred; the improvement was more marked in men where the mean baseline values of psychopathology were higher. There was also a significant decline of the mean numbers of positively evaluated items in 9 of 10 dimensions of the questionnaire. The drug was well tolerated by the patients with the exception of one transient allergic skin reaction. So far the exact ratio of improvement of psychopathology as a therapeutic response to sulpirid administration and the placebo effect on the patient's complaints cannot be exactly evaluated. Sulpirid has some advantages, as compared with other psychopharmaceutic preparations used in this indication (e.g. amitriptyline, dosulepine). PMID- 2225188 TI - [Psychoreactive disorders: clinical description of pathologic reactions, pathologic reactive states and reactive psychoses]. AB - After the introduction to the problem presented in the first part, the author submits a description of clinical units. The aim is to provide documentation of his concept and to unify the understanding of these conditions into a uniform system; conditions which, although adequately described, are included among different disorders and their classification and description is not uniform. The need of this description is urgent not only because the new generation of psychiatrists does not know the original classification but also because knowledge of these conditions has expended and this calls for new evaluation and description. PMID- 2225190 TI - [Relation between the effect of therapy and the course of neuroses in a day care sanatorium]. AB - In 152 patients who in 1979-1986 had a complete seven-week course of stationary treatment with daily group psychotherapy and who returned catamnestic questionnaires six months after termination of treatment, the relationship between the course of treatment and its effect was investigated. The effect of treatment was evaluated by the paired t-test. Ninety-eight patients improved significantly and 54 improved but not significantly. In these two groups the authors compared also the graphic presentation of the course of treatment as regards the grade of neurotic complaints, severity of the problem, activity at sessions and position in the group. The results indicate a favourable prognosis of treatment in patients with a subjectively conceived/higher position in the group and a rising activity at sessions. From what has been said ensues the importance to create an emphatic atmosphere in the group and to stimulate the activity of group members during treatment. PMID- 2225189 TI - [Psychiatric rehabilitation from the viewpoint of a large psychiatric facility]. AB - The paper makes the reader familiar with the results of activities of the central rehabilitation department in the Psychiatric Sanatorium in Kromeriz. It postulates views regarding the technique of work with patients and pays special attention to the rehabilitation of patients with schizophrenic psychosis. In these patients the results of rehabilitation care at different rating levels were evaluated. In the field of ergotherapy the schizophrenic patients were evaluated by the therapists and instructors of occupational therapy on entry of and departure from the workshop or class, using the Engelsman--Hajek scale. Based on the results the hypothesis was confirmed of a lower working performance of patients with schizophrenic psychosis, as compared with other diagnostic groups. In the field of remedial exercise and special forms of psychiatric rehabilitation, such as educational and recreational activities, patients with schizophrenic psychosis were evaluated by a doctor and psychologist of the rehabilitation department of the psychiatric sanatorium for after--treatment of psychoses. The patients were evaluated by Wing's scale for chronic schizophrenia and by means of the Scale for Evaluation of Working Performance and Behaviour. According to the results of both scales no significant differences were found between the experimental groups where different forms of rehabilitation were accentuated, as compared with the control group engaged only in occupational therapy. Both scales revealed in both experimental groups highly significant improvement as regards resocialization within a very short period during which the patients were subjected to intense rehabilitation. Based on these results the author recommends further rehabilitation provisions. PMID- 2225191 TI - [Canadian geriatric psychiatry and psychopharmacology 1987-1988]. AB - The paper offers a brief outline of the current state of geriatric psychiatry and psychopharmacology in Canada and partially in the USA. Major trends are described in clinical care, in organization and education, along with some basic historical comments. The important role of self-help groups is sketched. The contents of recent major scientific meetings illustrate the increasing emphasis in research in ageing, geriatric psychiatry and geriatric psychopharmacology. The developments are characterized by intimate connections between basic and applied research, and between clinical observations and experimental neurobiology. The analysis of developments in the current practice and research offers some insight into upcoming treatment strategies. The next decade in geriatric psychiatry will probably belong in particular to molecular biology, genetic, psycho-immunology and psychopharmacology. PMID- 2225192 TI - [80 years of social medicine in Prague]. PMID- 2225193 TI - [80 years of the Institute of Social Medicine, Organization and Health Care Administration of the School of General Medicine of Charles University]. PMID- 2225194 TI - [80 years of social medicine as an academic discipline]. PMID- 2225195 TI - [The profile of the physician-specialist in the field of social medicine and health care administration]. AB - The contributions to the discussion on the profile of medical specialists in social medicine and the organization of the health services were discussed by the Advisory Board of the main specialist of the Ministry of Health and Social Affairs CSR for the discipline of social medicine and organization of the health services on April 17, 1989. They are also in the already published first version published n Ceskoslovenske zdravotnctvi 37, 1989, No. 4, p. 145-150. PMID- 2225196 TI - [The status of implementation of the 38 goals of the WHO document "Health for All by the Year 2000" which were accepted by European member nations of WHO]. AB - The author gives an account of 38 targets adopted by 33 member countries of the European Region of WHO to implement the global world strategy "Health for All by 2000". Some required approaches for monitoring of the implementation of these targets are mentioned, as well as research trends outlined by WHO to promote these targets. The present position is evaluated, as well as prerequisites for the further implementation of WHO targets and relations with targets of the health policy in Czechoslovakia. In 1990 the European Regional Office of WHO will evaluate the regional targets in cooperation with member countries to simplify the monitoring. PMID- 2225197 TI - [Pharmacotherapy at the Ostrava area 1 pediatric first aid station]. AB - The author investigated the prescription of the most frequently recommended drugs at the medical first aid station in Ostrava 1 during the period 1985-1988, when a total of 53,212 children were treated. Most frequently antibiotics were prescribed--on average 33.8% with a maximum of prescription in the winter months. The second place was held by antipyretics, most frequently Acylpyrin, during the summer months--20.4%. PMID- 2225198 TI - [Teaching of medical ethics and law at a medical school]. AB - Medical practice calls for a highly ethical approach and responsibility codified also by law. Doctors should be trained in this respect also during undergraduate studies. At the Medical Faculty, Comenius University Bratislava there is relatively enough space for training in ethics and law which begins already in the introduction to medical studies and proceeds in the 5th, 9th and 10th semester in several medical and sociological disciplines. Knowledge evaluated by an investigation among sixth year students was only general, not adequate as regards medical law and even less adequate as regards medical ethics. Evaluation of the assembled knowledge by the students themselves slightly overestimates the legal responsibility and legal regulations and rated adequately their training in the sphere of ethics. PMID- 2225199 TI - [Present problems in health services and health care]. AB - In order to deal with and resolve contemporary problems of the health services and health care it is important to outline their concept, contents and definition as well as those of their fundamental constituents--the material, technical basis, workers and their activities, which determine the state health policy. The author analyzes from this aspect the hitherto accomplished development with regard to all basic constituents and discusses the problem of the relationship of the intensity and extensity of activities of the health services and health care. A foremost part is played by medical is played by medical science--medicine, its state, knowledge assembled by students during their undergraduate studies and medical graduates during their postgraduate training. A substantial and decisive component of the health services as regards therapeutic and preventive care is formed by health workers and the quality of their work which depends on objective as well as subjective factors which are analyzed. Health services do not comprise only practical activities but social medicine and the organization of health services are very important scientific disciplines which participate in the quality of activities. This scientific discipline was founded by prominent personalities. It must be stated that in practical medical work leading authorities do not always respect the scientific character of the discipline and thus very complicated problems arise as regards scientific control. All these problems from the aspect of the department of social medicine and organization of health services as well as subjective and scientific control must be resolved from the aspect of reconstruction of society. PMID- 2225200 TI - [The medical school and its training center at the District Institute of National Health in Nove Zamky from the viewpoint of medical students engaged in professional and social medicine summer practice]. AB - Within the framework of professional and social practice of medical students in the district institute of national health in Nove Zamky a questionnaire survey was made concerned with the attitudes and views of students as regards training at the medical faculties and as regards summer practice. The authors consider the information obtained from 37 students of different medical faculties in the SSR and CSR, ensuing from their first empirical experience in the field, a valuable feedback as regards the standard of training and shaping of the profile of the qualified doctor for practice. On the whole the students are satisfied with the conditions of practical work in Nove Zamky but have also some concrete concructive comments and suggestions for optimation and intensification of undergraduate training and therapeutic and preventive care. The participation of medical students in the above activities is a significant factor shaping their professional identity. PMID- 2225201 TI - [The creation and implementation of a information system for the health services]. AB - The author gives an account of the present state and near future as regards the use of computer technique in the health services, in particular the establishment of information systems. The author mentions the results achieved so far, comments on the preparation of a new orientation of Czechoslovak research in this sphere in 1990-1993. Finally he describes experience with the implementation of results of research into practice of Czechoslovak health facilities. PMID- 2225202 TI - [Relation of morbidity from gastric and duodenal ulcers with work disability and dispensarization]. AB - A retrospective investigation of the morbidity from peptic ulceration of the stomach and duodenum associated with work incapacity in 1985-1987 in workers of a large engineering factory provided evidence that personal data on this morbidity processed on a computer are along with the medical documentation of individuals a useful source of information for the selection and enlistment of patients into dispensary care and for its evaluation. The investigation revealed at the same time some methodological aspects of dispensarization. PMID- 2225204 TI - [Reform of the health services in West Germany and its economic impact]. AB - As a result of rationalization of labour, innovations in economy and the state administration, within the framework of scientific and technical development the FRG has greatly increased its investments and great social changes were implemented. The system of health services in the FRG is considered very efficient. The services are built on the principle on the patient's completely free selection of doctors. Specialists, research and technical facilities have a high standard. In 1988 a fundamental structural reform of the health services was implemented, due to the fact that the cost of health insurance has increased since 1960 three times faster than wages, whereby 13% of the insurance money has to be met by various additional payments. A further increase is not possible and therefore the entire reform of the structure of the health services was conditioned and governed by economic reasons. PMID- 2225203 TI - [Social determinants of health in the Czechoslovak population]. AB - The purpose of the submitted paper is to attempt to detect fundamental social factors which shaped the health status of the Czechoslovak population during the period since the Second World War. First attention is paid to the development of the health status. Subsequently the author characterizes briefly the basic spheres which influence health, i.e. the lifestyle, living and working environment and the activities of the health services. In the conclusion the author presents a characteristic of the socio-economic structure of Czechoslovak society as regards social relations. The author emphasizes the need of rapid transition to a truly democratic set-up of society and the implementation of fundamental economic reforms as the prerequisite for gradual improvement of the health status of the Czechoslovak population. Part of the contemplated social changes and at the same time an essential prerequisite of success is the implementation of the strategy of restoration and promotion of national health. PMID- 2225206 TI - [Methodical approaches to surveys of general morbidity in the population of other countries]. AB - General morbidity surveys of the population in western countries are based on interviews, while in socialist countries general morbidity surveys are usually done by direct medical examination or by assessment of the attended morbidity, most frequently, however, a combination of both approaches is used. Neither in interviews nor in the method based on direct or indirect medical examination so far sufficient unification of methodological approaches has been achieved to compare, based on these results, the health status of the population in different countries. PMID- 2225205 TI - [Methodical approach to a survey of general morbidity in Czechoslovakia]. AB - The author analyzes the method of general morbidity surveys conducted in Czechoslovakia between 1951 and 1985. The method of direct medical examinations was used as well as the method of "attended morbidity", but as a rule a combination of both these methods. During the mentioned period the procedure was not unified to make comparison of results possible. PMID- 2225207 TI - [Ambulatory care of diseases in children in selected areas of the Czech Republic]. AB - The author submits the results of a five-year investigation of ambulatory treatment of children in selected areas of the CSR. The original idea was to assess the morbidity of children in oecologically threatened areas. However, during the first two years it was revealed that the results do not meet the expectations of hygienists. The baseline material was the "Daily working record of the community paediatrician". The sample comprised 3% of the child population aged 0-14 years from all Czech regions except the South Bohemian one. PMID- 2225208 TI - [Prognosis in the mentally retarded child under the present conditions of institutional care]. AB - The environment of mentally retarded children suffers from fluctuations of staff in institutes for social care. The reasons are subjective and in the organization of work. As compared with other countries, there are differences in the categories of workers of these institutions as well as in their numbers and training. The concept of care of mentally retarded children has not been fully elaborated in this country so far. This has adverse repercussions on the working results in social care institutes and on the health status of mentally retarded children. PMID- 2225209 TI - [Possibilities of prevention of congenital developmental defects]. AB - One of the still open questions of teratology is the relationship between experimental teratological investigations and their validity in human medicine. The aetiology of the development of inborn developmental defects comprises factors the ratio of which is the subject of discussions. The category of still unknown factors is the largest one. This means that in 70% of inborn developmental defects there is nothing to go by. The influence of the deteriorated living or working environment need not be manifested by a higher incidence of seriously damaged foetuses. Comprehensive preconception care is a way which may lead to improvement in the sphere of prevention, although its application is not unequivocal. An essential prerequisite of effective prevention of inborn developmental errors is recognition of the causes of and laws governing their development. PMID- 2225210 TI - [Problems in home visit services in pediatrics]. PMID- 2225211 TI - [Registration of patients with chronic diseases]. AB - The authors describe registers of chronic diseases, provisions regarding their contents and organizational aspects. They make the reader familiar with the collection, storage and evaluation of data and some problems with their safeguarding. They report their experience with recommended questionnaires and the structure of forms. They describe the activities of the doctor completing the forms as well as the activities associated with recording in the centre. The authors demonstrate possible types of outputs and whom they serve. They illustrate the results of their work on the example of data from the register for diabetes mellitus of the juvenile type I and rheumatic fever. They discuss the role of registers in the health services, their role in ensuring the health status of the population, planning and management of the health services. In the conclusion they mention new technical possibilities. PMID- 2225212 TI - [Problems in our health services]. AB - The author draws attention to some problems of the contemporary health services which must be resolved in the near future. They comprise in particular the better use of the existing number of available beds and ambulatory diagnostic services. Among reasons for inadequate numbers of doctors the author mentions in particular superfluous consulting, examinations in conjunction with assessment of the work capacity, and administrative work done by many doctors. The author also mentions training of doctors, in particular for general practice. Among the causes of the low attractiveness of this discipline he mentions among others that examinations by the GP are, without any sound reason, not considered specialized examinations. Demands for a family doctor imply the patients' call for a more human approach. In the subsequent part the author pays attention to complaints and asks for the creation of a social climate in favour of new life as well as adequate terminal care of moribund patients. Finally he talks about a reform of our health services which will seek ways stimulating initiative, moral and material interest. PMID- 2225213 TI - [Socio-psychological, ethical and socio-hygienic aspects of preparation for the medical profession]. PMID- 2225215 TI - [Health status of the economically active population and drug consumption. II. Analysis of drug consumption]. AB - The authors pay attention to one of the indicators of the health status of the economically active population--to the consumption of drugs. The analysis was based on outpatient records on health and disease in a selected group of 2,080 patients (25.9% of the basic group) in relation to sex, age and work capacity. The drug consumption of persons unable to work was cca 40% of the total drug consumption, whereby a higher consumption was recorded in women. With advancing age the drug consumption in diseases not associated with work incapacity rises markedly. Age practically does not influence the drug consumption on account of diseases causing work incapacity. PMID- 2225214 TI - [The present status of tuberculosis in the Slovak Republic]. AB - In 1988 the incidence of newly detected cases of TB in the Slovak Republic was 31.6/100,000 population. As compared with 1987, a decline of the disease by 9.8% was recorded. Its incidence in the SR shifts to higher age groups. The prevalence of active tuberculosis reached in 1988 34.4 and the mortality 0.4/100,000 population. Despite these relatively favourable indicators, TB remains in the SR a public health issue which will require also in future systematic attention and care. PMID- 2225216 TI - [Personal experience with examination of the small intestine using the enteroclysis method]. AB - Enteroclysis is rightly included to modern diagnostic methods for detecting damage to alimentary canal. It enables to visualize even small morphological changes on the mucous membrane of intestine, to prove fistulas if present and to evaluate functional changes if correctly applied. It significantly contributes to establishing early diagnosis in affections of the intestine and consequent use of adequate therapy. The authors in their communication summarized their experience, obtained in the examination of one hundred patients. They selected a modified procedure of examination according to Herlinger with the use of Prontobarium suspension and methyl cellulose. The application was made with a controlled duodenal probe from the Nicholas Company, introduced by nose. The average duration of one examination was 44 minutes. PMID- 2225217 TI - [Computer tomography in the diagnosis of hyperparathyroidism]. AB - The paper presents long-term experience in the diagnosis of hyperparathyroidism by means of computer tomography. A large number of examinations (164) of parathyroid glands, the possibility of verification and comparison with sonography or with other diagnostic methods of visualization make it possible to define the role of computer tomography in hyperparathyroidism and to show advantages and limitations of the method. For the high diagnostic precision the CT examination may be considered to be the reliable method in the demonstration of enlarged parathyroid glands. PMID- 2225218 TI - [The picture of focal liver disease in ultrasound, computer tomography and angiography]. AB - In a group of 25 patients examined by sonography, computer tomography and angiography with diagnoses confirmed during operation and by histology, the author compared the efficiency of the individual methods and a complex examination. Computer tomography proved to be the most efficient method which enabled, in addition to precise localization, appreciation of size and relation of the pathological focus to adjacent structures, to determine their nature in some. The complex examination in indicated cases significantly increased the diagnostic efficiency. PMID- 2225219 TI - [Tracheobronchography in neonates and infants with obstruction of the upper respiratory tract]. AB - In the period of 1980 to 1989 the authors performed contrast examinations of tracheobronchial tree in 38 children up to one year of age, three of them being newborns. In 29 examined children (74.4%) there was an anatomical defect causing the obstruction of upper respiratory pathways. In 15 of them the trachea compression was caused by pressure of hyperplastic thymus on the brachiocephalic arterial truncus crossing trachea. For visualization of upper respiratory pathways Hexabrix 320 (Byk Gulden) was used in 30 children, administered in 10 cases by jet ventilation. The filling was recorded by radiocinematographic method. PMID- 2225220 TI - [Thermography findings in the hands in relation to the age of the examined individual]. AB - The authors compared thermographic findings of hands in two groups of apprentices (average age 15 and 16 years) with a group of students (average age 21 years) and a group of young workers (average age 29 years). There was a highly significant difference in the number of cold hands before and after vibration test in the apprentices and adults (29 years). The authors arrive at the conclusion that 1) thermoregulation reaches its final shape only after 20 years of age, 2) in the apprensitive thermographic finding must be verified by regular thermographic control examinations. PMID- 2225221 TI - [Pseudotumor of the left epigastrium]. AB - The authors describe the case of a patient with an accessory spleen located between the spleen and upper pole of the left kidney. A repeated sonographic examination suggested a suspicion for a kidney tumour, shape anomaly of the spleen, accessory spleen or kidney, but did not exclude even benign tumour in retroperitoneum. Computer tomography proved a formation between the upper pole of the kidney and the spleen, whose density characteristic after a rapid intravenous injection of 60% Verografin at the amount of 1 ml per kg body weight was the same as that of the spleen. Only angiographic examination revealed that the case is an accessory spleen and not a tumour. PMID- 2225222 TI - [Anomalous branching of the inferior thyroid artery from the left vertebral artery]. AB - In a 53 years old woman hospitalized for a suddenly developed picture of vascular insufficiency in the verterobrobasillary vascular bed the authors detected an anomalous division of the left vertebral artery from aortic arch. Moreover, at the level of thyroid gland there was the division of inferior thyroid artery from the vertebral artery. We express the opinion that the finding did not participate in the clinical symptomatology. PMID- 2225223 TI - [Occlusion of a pseudoaneurysm of the internal carotid using a catheterization technic]. AB - The authors describe a successful therapeutic occlusion of the left internal carotid artery in a five years old boy by the catheterization technique. The intervention treated a pseudoaneurysm originating after incision of a peritonsillar abscess. PMID- 2225224 TI - [Amiodarone pulmonary toxicity]. AB - The authors describe their observation of the amiodarone toxic lung not having been published in this country before. Data in its occurrence in literature with an outline of differential diagnostic possibilities in a successful establishment of diagnosis in this female patient are presented. PMID- 2225225 TI - [Results of transabdominal chemical sympathectomy of the lower extremities directed by computer tomography]. AB - The authors evaluated 47 transabdominal lumbar sympatectomies by ethyl alcohol with a control by computer tomography in surgically unsolved disorders in the passage through lower extremity arteries. In four fifths of the patients there was an increase in ischaemia manifestations, in one fifth there was no improvement. No substantial difference was found between the results of sympatectomy in diabetic and nondiabetic patients. The method should be applied sooner than a cutaneous ischaemic defect develops. PMID- 2225226 TI - [Microdosimetry characteristics of ionizing radiation in the nanometer range]. AB - A calculation method of microdosimetrical quantities epsilon D and yD using the proximity function t(x) of the delta rays of an incidental radiation is introduced. In comparison with classical Monte-Carlo calculation, the presented method is simpler and faster. Therefore there is the possibility to calculate effectively the microdosimetrical quantities in a large scale of the dimension of the volumes from 10(-9) to 10(-6) m and for various energy spectra of ionizing particles of a different kind. The presented method was verified low energy electrons and X-ray. Our results are in good agreement with published data. PMID- 2225227 TI - Oxygen radicals in intestinal ischemia and reperfusion. AB - Intestinal ischemia, however, caused, is still a serious and growing clinical problem with an unacceptable mortality rate of over 60%. This high mortality rate is mainly due to the fact that the patients are not admitted to the hospital or not treated early enough. Even if the patients are operated on within 24 h, their mortality rate is still over 50%, and those surviving the initial treatment suffer from postischemic complications. These damages have been accounted until now to tissue ischemia. It has been proven experimentally that also reperfusion or revascularization after time-limited ischemia add to the tissue damages observed, due to the formation of O2-radicals. Thereby the prerequisites for the production of these radicals (the conversion of xanthine dehydrogenase to xanthine oxidase and the increase of hypoxanthine concentrations in the tissue and plasma) are generated during tissue ischemia. These radicals damage directly or initiate several vicious circles leading to mucosal lesions, impaired intestinal function and an enhanced absorption of bacteria and endotoxin. Various substances (SOD, catalase, DMSO, allopurinol, deferoxamine etc.) detoxify oxygen radicals or inhibit the pathomechanisms leading to the enhanced radical generation. Hopefully, the combination of early revascularization with these already available scavengers will improve the high mortality and morbidity of patients suffering from intestinal ischemia. PMID- 2225228 TI - Effects of 1-ethynylpyrene and related inhibitors of P450 isozymes upon benzo[a]pyrene metabolism by liver microsomes. AB - The effects of three aryl acetylenes, 1-ethynylpyrene (EP), 2-ethynylnaphthalene (EN) and 3-ethynylperylene (EPE), upon the metabolism of benzo[a]pyrene (BaP) by microsomes isolated from rat liver were investigated. These aryl acetylenes all inhibited the total metabolism of BaP. Formation of BaP 7,8-dihydrodiol and BaP tetrol products by microsomal preparations from rats that had been pretreated with 3-methylcholanthrene (3MC) were preferentially inhibited. The effects of EP upon the metabolism of BaP 7,8-dihydrodiol by microsomes from rat liver were also studied. This aryl acetylene strongly inhibited the formation of BaP tetrols from BaP 7,8-dihydrodiol by liver microsomes both from untreated rats and from rats pretreated with 3MC, but enhanced the conversion of the BaP dihydrodiol into other metabolites. PMID- 2225229 TI - The oxidation of the highly tumorigenic benz[a]anthracene 3,4-dihydrodiol by rat liver dihydrodiol dehydrogenase. AB - Rat liver dihydrodiol dehydrogenase (DDH, EC 1.3.1.20) has been shown to reduce the mutagenicity of benz[a]anthracene (BA) in the bacterial Ames test. BA-3,4 dihydrodiol is a highly mutagenic and tumorigenic metabolite of BA. In order to test the hypothesis that this dihydrodiol may be a substrate of DDH, we established two novel assay systems for the NADP(+)-dependent oxidation of BA-3,4 dihydrodiol by rat liver DDH, an HPLC-based assay procedure and a radiometric assay with specifically labelled [3,4-3H]-BA-3,4-dihydrodiol as substrate. With the HPLC-based assay, the kinetic constants of the enzymatic catalysis were as follows: Km(app) = 21 microM for BA-3,4-dihydrodiol and Vmax = 20.0 nmol/min.mg enzyme. The reaction product was identified by cochromatography, fluorimetry and mass spectroscopy as BA-3,4-catechol, but interconversions between the catechol and the corresponding o-quinone during the analytical procedures were detected. With the radiolabelled substrate, a linear relationship between substrate concentration and reaction velocity was found. The V/K value for labelled substrate was 0.155 ml/min.mg enzyme and a (V/K)H/(V/K)T kinetic isotope effect of 6.7 was observed. The non-labelled substrate acted as a competitive inhibitor of the enzymatic oxidation of tritiated BA-3,4-dihydrodiol with a Ki value of 56.4 microM. The reaction rates determined in this study suggest an important role of DDH activity in the metabolism of BA. PMID- 2225230 TI - Quinone imine-induced Ca2+ release from isolated rat liver mitochondria. AB - Incubation of Ca2(+)-loaded rat liver mitochondria with N-acetyl-p-benzoquinone imine (NAPQI) or its two dimethylated analogues resulted in a concentration dependent Ca2+ release, with the following order of potency: 2,6-(Me)2-NAPQI greater than NAPQI greater than 3,5-(Me)2-NAPQI. The quinone imine-induced Ca2+ release was associated with NAD(P)H oxidation and was prevented when NAD(P)+ reduction was stimulated by the addition of 3-hydroxybutyrate. Mitochondrial glutathione was completely depleted within 0.5 min by all three quinone imines, even at low concentrations that did not result in Ca2+ release. Depletion of mitochondrial GSH by pretreatment with 1-chloro-2,4-dinitrobenzene enhanced quinone imine-induced NAD(P)H oxidation and Ca2+ release. However, 3 hydroxybutyrate protected from quinone imine-induced Ca2+ release in GSH-depleted mitochondria. Mitochondrial membrane potential was lost after the addition of quinone imines at concentrations that caused rapid Ca2+ release; however, subsequent addition of EGTA led to the complete recovery of the transmembrane potential. In the absence of Ca2+, the quinone imines caused only a small and transient loss of the transmembrane potential. Taken together, our results suggests that the quinone imine-induced Ca2+ release from mitochondria is a consequence of NAD(P)H oxidation rather than GSH depletion, GSSG formation, or mitochondrial inner membrane damage. PMID- 2225231 TI - Differences in sequence selectivity of DNA alkylation by isomeric intercalating aniline mustards. AB - Two DNA-targeted mustard derivatives, N,N-bis(2-chloroethyl)-4-(5-[9 acridinylamino]-pentamido)aniline and 4-(9-[acridinylamino]butyl 4-(N,N-bis[2 chloroethyl]-aminobenzamide, which are isomeric compounds where the mustard is linked to the DNA-binding 9-aminoacridine moiety by either a -CONH- or a -NHCO- group, show significant differences in the sequence selectivity of their alkylation of DNA. The CONH isomer is a more efficient alxylating agent than the NHCO compound by an order of magnitude, consistent with the larger electron release of the CONH group to the aniline ring. However, the pattern of alkylation by the two compounds is also very different, with the CONH isomer preferring alkylation of guanines adjacent to 3'- or 5'-adenines and cytosines (for example those in sequences 5'-CGC, 5'-AGC, 5'-CGG and 5'-AGA) while the isomeric NHCO compound shows preference for guanines in runs of Gs. In addition, both isomers alkylate 3'-adenines in runs of adenines. Both compounds also show completely different patterns of alkylation to their untargeted mustard counterparts, since 4-MeCONH-aniline mustard alkylates all guanines and adenines in runs of adenines, while 4-Me2NCO-aniline mustard fails to alkylate DNA at all. These differences in alkylation patterns between the CONH- and its isomeric NHCO- compounds and their relationships between the alkylation patterns of the isomers and their biological activities are discussed. PMID- 2225232 TI - Renal proximal tubular cells in suspension or in primary culture as in vitro models to study nephrotoxicity. AB - The kidney forms a frequent target for xenobiotic toxicity. The complex biochemical mechanisms underlying nephrotoxicity are best studied in vitro provided that reliable and relevant in vitro models are available. Since most nephrotoxicants affect primarily the cells of the proximal tubules (PTC), much effort has been directed towards the development of in vitro models of PTC. This review focuses on the preparation of PTC and the use of these cells. Discussed are important criteria such as the viability (survival time) of the cells and the parameters to assess toxicity. Recent studies have shown that isolated PTC in suspension are especially suitable for studies on the biochemical mechanisms of 'acute' nephrotoxicity, whereas PTC in primary culture may be used to investigate mechanisms of nephrotoxic damage at very low concentrations, upon prolonged exposure. PTC cultured on porous filter membranes provide new possibilities to study toxicity in relation to cell and transport polarity. Primary cell cultures of human PTC have been set up. Although a further characterization of these systems is needed, recent data indicate their usefulness. PMID- 2225233 TI - Thiol antidotes effect on lipid peroxidation in mercury-poisoned rats. AB - The effect of thiol antidotes 2,3-dimercapto-1-propanesulfonic acid (DMPS) and D penicillamine (PA) on lipid peroxidation and on activities of some protecting enzymes in blood, liver and kidneys of mercury-poisoned rats has been studied. It has been found that Hg-poisoning is associated with increased lipid peroxidation in the liver and in the kidneys and with inactivation of superoxide dismutase (SOD) and catalase. Inhibition of SOD is caused by thiols treatment too, but in this case acceleration of lipid peroxidation has not been observed. Evidence is presented that in the liver, protection against mercury-induced lipid peroxidation is afforded by both thiols, while in the kidneys only PA has protective effect. In in vitro experiments it has been demonstrated that both antidotes can act as O2- scavengers and lipid peroxidation inhibitors, but PA is significantly more effective. On the basis of the obtained results a conclusion is drawn that in addition to the metal-removing ability, the antioxidant properties of the chelating agents may play an important role in manifestation of their beneficial effect in metal intoxications. PMID- 2225234 TI - Schedule dependence of buthionine sulfoximine in reversing resistance to cisplatin. AB - We have found that the potentiation of antiproliferative effects by buthionine sulfoximine (BSO) of cell growth inhibition induced by cisplatin are highly schedule dependent in resistant BE colon carcinoma cells. Maintenance of low GSH levels during the 12-h interval after cisplatin (cis-DDP) treatment is critical. A schedule of BSO exposure that results in low GSH levels for 12 h after cisplatin exposure is associated with a marked increase in DNA interstrand cross link formation as analyzed by alkaline elution. These findings are consistent with a central role of GSH in interfering with the conversion of cis-DDP DNA monoadducts to DNA interstrand cross-links and may prove relevant to the design of clinical trials of BSO with cisplatin. PMID- 2225235 TI - Acute and long-term effects of carbon tetrachloride on DNA modifications (I compounds) in male mouse liver. AB - I-compounds are recently discovered species and tissue dependent covalent DNA modifications which are detectable by the 32P-postlabeling assay for DNA adducts and tend to increase with the animal's age. The effects of the hepatocarcinogen carbon tetrachloride (CCl4) on hepatic I-compounds were studied in 10-12-month old male ICR mice using the 32P-postlabeling assay. CCl4 was dissolved in corn oil (20%, v/v) and intraperitoneally (i.p.) injected in doses of 0.75 ml/kg (0.375 ml/100 g body weight, 20% CCl4 in corn oil) while control mice received corn oil only (0.375 ml/100 g body wt). Twenty-four h after a single injection of CCl4, the intensity of non-polar I-spots in liver DNA was significantly increased as compared with corn oil treated controls, while the level of one polar I compound was reduced at 24 h. DNA synthesis (as indicated by [3H]thymidine incorporation) was not significantly affected at 24 h after a single dose of CCl4. To study the long-term effects of CCl4, five groups of mice were given two consecutive weekly injections of 0.75 ml/kg CCl4 (as above) and were sacrificed 1, 4, 8, 12 and 22 weeks after the second treatment. In these groups the total liver I-compound levels were reduced to 17.3-49.0% compared with corresponding controls. The maximum decline was observed at 4 weeks (17.3% of control). Comparison of thymidine incorporation showed no significant increase between control and treated liver DNAs at 1, 4 and 8 weeks after CCl4, suggesting that the decrease in I-compound levels was probably not a secondary effect of increased DNA synthesis during postnecrotic proliferation. Even though there was a trend of recovery between 8 and 22 weeks, I-compound levels still remained significantly lower at 22 weeks (49.0%). Since I-compounds appear to be normal DNA modifications, the results suggest that persistent reduction of I-compound levels contributes to the hepatocarcinogenic effect of CCl4. PMID- 2225236 TI - Magnetic alignment and orientational order of dipalmitoylphosphatidylcholine bilayers containing palmitoyllysophosphatidylcholine. AB - Mixed bilayers of 1-palmitoyl-sn-glycero-3-phosphocholine (palmitoyllysophosphatidylcholine; PaLPC) and 1,2-dipalmitoyl-sn-glycero-3 phosphocholine (dipalmitoyl phosphatidylcholine; DPPC) have been investigated by 2H-NMR and 31P-NMR spectroscopy. Binary phospholipid mixtures were studied in which the acyl chains of one or the other component were perdeuterated. At temperatures below the main order-disorder phase transition, the mixed PaLPC/DPPC bilayers appear to coexist with PaLPC micelles. The micelles disappear at temperatures above the phase transition, where mixed bilayers in the liquid crystalline state are formed. The orientational order of the alkyl chains of the PaLPC component is essentially identical to that of the DPPC component in the mixed bilayers, both in the low temperature and liquid-crystalline phases. However, the presence of PaLPC perturbs the segmental ordering of DPPC as compared to the pure system. The order is increased in the low-temperature phase, where effective diffusion of the chains about their long axes occurs, but is decreased in the liquid-crystalline phase compared to pure DPPC bilayers. The mixed liquid-crystalline bilayers orient preferentially with their director axes perpendicular to the magnetic field. This alignment is easily observed in 31P- and 2H-NMR spectra, where the intensity of the perpendicular edges of the lineshapes is pronounced. One possible explanation of the magnetic alignment involves alteration of the curvature free energy of the DPPC bilayer due to incorporation of PaLPC in the mixed membranes. PMID- 2225237 TI - Mass spectrometric analysis of O-peracetylated derivatives of 1 monomycoloylglycerol isolated from Corynebacterium pseudotuberculosis, Rhodococcus rhodochrous and R. lentifragmentus. AB - 1-Monomycoloylglycerols from Corynebacterium pseudotuberculosis, Rhodococcus rhodochrous and R. lentifragmentus were reacted with acetic acid ahydride in the presence of pyridine. On infrared spectra the reaction products showed a sharp characteristic absorption of the acetyl ester group at 1235 cm-1; the hydroxyl group absorption (3400 cm-1) was absent. O-Peracetylated monomycoloylglycerols were analyzed by mass spectrometry under electron impact mode. The most common and representative peaks were associated to the following remarkable fragments: (a) peak at m/z 159 represented the backbone of the glycerol unit of peracetylated monomycoloylglycerols; it constituted the diagnostic and base peak of that group of compounds; (b) peak representing the glycerol moiety together with the alpha-subunit of the mycolic acid moiety; it gave the size of the chain length of the hydrocarbon side chain of that mycolic acid; and (c) a series of peaks of acylium ions minus 60 mass units (acetic acid) indicated the size of the chain length of the esterified mycolic acid. Therefore, acetylation of monomycoloylglycerol becomes the derivatized compound suitable for mass spectrometry. Moreover, the derivatives are more thermostable and resistant to pyrolysis. By associating these properties, separation and identification of homologs of monomycoloylglycerols are further expected. PMID- 2225239 TI - Nursing research is not progressing. PMID- 2225240 TI - The health needs of the black elderly population in certain areas of rural and urban Kwazulu. AB - The health needs of Black elderly in rural and urban KwaZulu was investigated through a survey. Interviews with 240 elderly was done, looking at the first and second level of the health facilities plan, as well as social support and health indicators. It was found that urban elderly are generally better off than rural elderly and a profile of need is described. PMID- 2225238 TI - Influence of alkali metal cations on the transport of calcium by phosphatidate in multi-phase systems. AB - The effects of alkali metal cations on the rates at which Ca2+ and phosphatidic acid were cotransported from aqueous to hydrocarbon medium were examined. The alkali metal cations remained in the aqueous phase yet specifically influenced the transport of Ca2+ into the hydrocarbon solvent. For the physiological cations, Na+ and K+, there were critical concentration ranges in which small changes in concentration effected sharp changes in transport rates. The maximal rate observed with Na+ was an order of magnitude greater than that with K+; however, unlike Na+, K+ promoted low levels of transport below the critical concentration range. Li+ effected only low levels of transport even at high concentrations, whereas Rb+ and Cs+ induced transport at rates proportional to their concentrations. These results are discussed in terms of a classical ionophore model for the complex composed of a neutral phosphatidic acid dimer bridged by Ca2+. PMID- 2225241 TI - Standards for the nursing care of the frail aged. AB - In this project standards for the nursing care of the institutional care of the frail aged were formulated and then validated by groups of nurses. An instrument was then designed to measure to what extent these standards are reached. The instrument was then tested for reliability and validity in a sample of 12 institutions in the Eastern Cape and Natal. PMID- 2225243 TI - The quality of nursing care of the frail aged in selected institutions in eastern Cape and Natal. AB - An investigation was undertaken to establish standards for the care of the frail aged and to develop an instrument to measure this care. In this process the care in 12 institutions was monitored. In general, the care was found to be of good quality, with an average of 74.3%, but there are residences where the percentage is up to 10% lower. The influence of some internal and external factors on the quality of care were investigated. PMID- 2225242 TI - The combating of tuberculosis: health perceptions, intentions and vaccination of children. AB - This study was part of a comprehensive research project undertaken at the request of the SANTA Health Education Committee to evaluate the tuberculosis guidance programme. The aim of the research was to examine factors influencing black people's health perceptions and intentions concerning the combating of tuberculosis as well as vaccination of their children. Data were collected by means of a questionnaire based on the Health Belief Model. The research was conducted in selected areas of the OFS, the Transvaal and Natal (N = 1,198). It was found that factors indicating a greater degree of development of the individual (e.g. literacy) were positively associated with positive health perceptions such as that medical treatment can cure TB completely. Some positive associations were also found between perceptions/modifying factors and intentions/vaccination. Indications were also found of an inability on the part of health personnel to influence the public positively. PMID- 2225244 TI - The role of the nursing staff in promoting the development of preterm infants through their contribution to mother-infant interaction. AB - Preterm birth constitutes a potential risk factor for infant development. There is evidence that parental sensitivity and responsivity can compensate for biological risk. Since the birth of a preterm infant often constitutes a crisis for parents, they may be impaired in their ability to relate appropriately to their infants. The nursing staff can play a vital role in enhancing the interaction between parents (in particular mothers) and their preterm infants, thereby indirectly promoting optimal infant development. This paper describes the psychological tasks faced by mothers of preterm infants, parents' experiences of preterm birth and suggestions as to what the nursing staff can do to facilitate healthy relationships between parents and their preterm infants, thereby preventing possible pathological development. PMID- 2225245 TI - [A study of job satisfaction of nurses of the RSA (South Africa Nurses' Association)]. AB - The purpose of this study was to determine whether changes had occurred in the work satisfaction of nursing services after the establishment of private initiative in health care due to the deregulation program currently conducted by the government. In a survey conducted in the latter part of 1988 700 questionnaires were sent out of which 213 were returned which gives a response of 30.43 percent. The analysis was based on this data. The attitudes of the members of the nursing services ranged from antipathy to lively enthusiasm. It was, however, clear from the response that there exists a strong negative view amongst the nursing profession regarding remuneration, communication, training and promotion. These are tendencies that can harm the profession as a whole on the long run and should therefore receive special managerial attention. Recommendations include market related remuneration, continued nursing training, and planned career paths, as well as an appeal that only minimum admission requirements should be accepted as preconditions to training in order to cope with the growing Third World demands on health care services. PMID- 2225246 TI - The experience of black parents/caretakers with the births and care of a child with profound congenital defects. AB - The reaction of Black families to the birth and care of a baby with profound congenital defects was researched using twenty case studies. It was found that the families went through stages of the grieving process, that they shifted from the Western/Christian viewpoint to the traditional viewpoint in their struggle to cope and that they find the existing services grossly inadequate. PMID- 2225247 TI - Dealing with a patient with a profound congenital defect. PMID- 2225248 TI - Teaching caring in nursing: a needs assessment. AB - Despite the fact that caring is the heart of nursing, there is growing evidence that nurses are not as effective as they ought to be in their caring role. This signifies that more attention needs to be given to the teaching of caring. The aim of this study was to pave the way to initiate the process of research on teaching caring, by suggesting priority areas. The needs assessment design was used for the study. Five steps were involved to achieve the aims. The first was to explore the nature and meaning of caring as presented in the literature. The second was to review completed research on aspects of caring within the nursing context. The third was to investigate the position of caring in the present nursing education system. The fourth was to investigate ways of promoting the teaching of caring as advocated in the literature and the final step based on inferences made from the first four steps was to suggest priority areas for research on teaching caring in nursing. PMID- 2225249 TI - [Standards of patient education for nursing practice in general hospitals]. AB - A lack of patient education standards was identified and the researchers attempted in this study to develop standards for patient education. An instrument for the evaluation of patient knowledge was also developed. PMID- 2225250 TI - [Standards for making a community diagnosis]. AB - Standards for the making of a community diagnosis were formulated and validated on a national basis. These standards can be utilised by the community health nurse to improve the quality of community diagnoses. The quality of community diagnosis by community health nurses, was analysed by means of a retrospective audit. Incomplete diagnosis were observed in the compilation of a community profile and data resources were inadequately utilised. Important health indicators were not taken into account during the interpretation of data and planning strategies were incomplete. It appears as if the community health nurse tends to pay more attention to data that is readily available or can be utilised for quick results in his/her community planning. PMID- 2225251 TI - [Our experience with Yag laser in the treatment of secondary cataract]. AB - The authors report 168 cases of opacification of posterior capsule treated by Yag laser capsulotomy. They describe the operating technique, the results, the complications and the indications. PMID- 2225252 TI - [Retinal detachment in patients with pseudophakia]. AB - 49 eyes with pseudophakic retinal detachments are operated with 44 good anatomic results (90% success). These detachments are characterised by the high frequency of anterior proliferative vitreoretinopathy. PMID- 2225253 TI - [MALT conjunctival lymphoma: how to treat?]. AB - A case of conjunctival lymphoma belonging to the MALT tissue is reported hereby. It is very uncommon in the literature, but special tools are needed to recognize this conjunctival involvement: Frozen sections of tissue to perform immunocytochemical studies. Investigations of the other lymphoid tissue, to assess the localized feature of the conjunctival disease. PMID- 2225254 TI - [Neonatal dacryocystitis. A case report]. AB - The authors report one case of neonatal dacryocystitis. They consider the diagnostic and therapeutic problems. One surgical intervention, with a large orifice of the lacrimal meatus, upon the catheter, with rhinoscopy, seems them the best solution, in this precise case. PMID- 2225255 TI - [Poisoning of retinal pigment epithelium by deferoxamine. A case report]. AB - A patient undergoing hemodialysis was treated intravenously with desferrioxamine (3 g) for an aluminum encephalopathy. He presented a sudden xanthopsia with visual loss. Fundus examination showed diffuse macular irregular pigmentary disturbances. We discuss current knowledge and possible pathogenesis of these observations published since 1983. Awareness of the side effects of desferrioxamine implies an ophthalmologic follow up similar as chloroquine. PMID- 2225256 TI - [Uncommon site of retinal periphlebitis in a case of multiple sclerosis]. AB - The authors study an observation of unusual localisation, near the optic disc, of periphlebitis associated to multilocular sclerosis. There are some cicatricial periphlebitis and active others, which are more peripheral, alone without any uveitis. These ones resolved in two months with cortisone treatment. PMID- 2225257 TI - [Intravitreous hemorrhage caused by retinal tear with a bridge vessel. Discussion on management of 4 cases]. AB - The authors report 4 cases of recurrent vitreous hemorrhage related to retinal breaks without detachment, bridged by a retinal vessel. Clinical and evolutive features of this type of breaks are emphasized according to a review of available literature. Fluoroscopic evaluation of vascular permeability appears as a promising prognostic tool. Management should be directed to the prevention of both retinal detachment and vitreous hemorrhage recurrence. Cryoapplication and scleral buckling is far more effective than photocoagulation. PMID- 2225258 TI - [Corneal transplantation and histocompatibility of the HLA system]. AB - The HLA antigens appear to be involved in the rejection of corneal allografts. A relationship exist between HLA compatibility and the corneal rejection-free transplant survival. Eleven corneal transplants are performed on the basis of the best available HLA A and B match. Rejection-free transplant in this group is compared to a control group. The estimate rejection-free survival is 82%. PMID- 2225259 TI - [Oculorespiratory reflex]. AB - The lack of interest about oculorespiratory reflex (ORR) in surgery and experimental studies is obvious. However the authors insist on the importance of its clinical traduction. The purpose of this study is to determinate an experimental model with titration of stimulus (pressure or traction) and therapeutic test. Our first Results prove the clinic entity of O.R.R. In first conclusion, we can insist on the importance of ventilatory assistance during squint surgery and on the monitoring of PE CO2 and Sa O2. PMID- 2225260 TI - [Epidemiologic aspects of acute anterior optic neuropathies]. AB - The authors report 34 cases of anterior ischemic optic neuropathy, in 31 patients with one complete etiological examination. The modes of revelation, the symptoms and the results of the etiological inquest are related. PMID- 2225262 TI - [A new anesthetic protocol in experimental ocular surgery in rabbits]. AB - The authors describe a new anaesthetic protocol for laboratory rabbits. The surgery consists in an extracapsular lens extraction with intraocular lens implantation in the bag. The anaesthetic protocol requires: an intravenous induction with ketamine (20.2 mg/kg +/- 5) and midazolam (0.65 mg/kg +/- 0.3) and after an oral endotracheal intubation with a simple method, and at last maintaining halothane anaesthesia with a concentration between 3 and 4%. 45 anaesthesia were performed: the average time of the anaesthesia was 77 min +/- 16. No rabbit died because of this anaesthesia. The anaesthesia was a success for the surgeon who could operate in the best working conditions. PMID- 2225261 TI - [Intraocular penetration of topical norfloxacin in humans. Preliminary study]. AB - The aim of this bicentric study was to assess the intraocular penetration of topical Norfloxacin. Herein, are only reported the results from one center. Topically applied Norfloxacin 0.3% was given to patients who underwent cataract surgery. The first group received 5 drops between 7.55 A.M. to 8 A.M. and after each hour until cataract surgery. The second one received one drop each quarter from 7 A.M. until the surgery. Aqueous and sera samples were dosed using HPLC. In the first group, the aqueous average was 0.066 mg/l and 0.112 mg/l in the second group. Using a T test and Mann Whitney test, we could not find a significant difference between the two groups. PMID- 2225263 TI - [Chorioretinal coloboma and neovascular membrane]. AB - Retinochoroidal coloboma results from an incomplete closure of the ocular embryonic fissure. Uni or bilateral, the coloboma can be associated with cataract, microphthalmia, retinal detachment... but rarely with neovascularization. This association is comparable with subretinal neovascularization in high myopia, angioid streaks, choroiditis and choroidal ruptures. The disruption of the normal anatomy of the Bruch's membrane is a possible entry site of choroidal blood vessels. But the reason why only rare cases are reported is unknown. PMID- 2225264 TI - [Pyocyanic corneal abscess]. AB - The authors report 3 different cases of pseudomonas abscess of the corneal layers: these occurred; one on a soft lens; the second one apparently without any reason; the last one 2 days after a corneal traumatism. In spite of rapidly administrated antibiotherapy, the abscess spread very rapidly and left a residual corneal macula. PMID- 2225265 TI - [Bacteriologic examination of the conjunctiva immediately prior to surgery]. PMID- 2225266 TI - [Iatrogenic pigmentary glaucoma after implantation (Iogel)]. PMID- 2225267 TI - [Functional outcome of advanced chronic glaucoma after trabeculectomy]. AB - We studied the risk of sudden loss of visual fields after trabeculectomy on 17 eyes with primary open angle glaucoma and small residual visual fields. We think that it is possible to try to these patients filtering procedures with precautions before and during surgery. PMID- 2225268 TI - [Preoperative biometry. Statistics and conclusions. Report of 330 artificial lens implantations]. PMID- 2225270 TI - [Keratoscopy in cataract surgery]. AB - The peroperative keratoscopy is a subjective method with approximates results (error of 30% on medium power of astigmatisme postoperative). Its advantages with regard to peroperative keratometry are its simplicity, quickness, non-expansivity and efficiency. PMID- 2225269 TI - [Uselessness of electroretinogram for detecting retinal poisoning by synthetic antimalarials]. AB - Authors present two cases of typical macular "bull's eyes" other APS treatment with subnormal electric answer. They evocate the poor sensibility of the different methods used to detect and follow these patients and propose a more sensible, easier and test accepted test: static perimetry within the 12 central degrees, once or twice a year. PMID- 2225272 TI - [Subretinal neovessels in diffuse retinal epitheliopathy]. PMID- 2225271 TI - [Macular manifestations of acute lymphoblastic leukemia. A case report]. AB - The authors report a case of ocular involvement by acute lymphoblastic leukemia, in a young woman. The initial symptom was a bilateral diminution of visual acuity. The examination revealed a bilateral aspect of serous detachment of neuro epithelium. A literature review of macular manifestations of leukosis is envisaged. PMID- 2225273 TI - [Contrast sensitivity]. PMID- 2225274 TI - [Basedow's neuropathy]. AB - A case report of grave's neuropathy. The symptoms appeared in a treated patient when there was a biologic hypothyroidy. A total remission was observed after corticotherapy. Nevertheless, a recurrence of disease happened for reduced doses, so an orbital radiotherapy was requisited. Student of differents treatments for dysthyroid neuropathy. PMID- 2225275 TI - [Optic disk drusen and intracranial tumor]. AB - A fifty-one year old woman with a Lindau sickness presented bilateral optic disc swelling and peripapillary haemorrhage. Intracranial hypertension was suspected. Perimetry, echography and fluorescein fundus angiography revealed optic disc drusen. PMID- 2225276 TI - [Pachymetry in radial keratotomy]. PMID- 2225277 TI - [Automatic perimetry. The myth and reality]. PMID- 2225278 TI - [Visual aids using hypernegative artificial lens in age-related macular degeneration]. PMID- 2225280 TI - [10 years' evaluation of systematic refraction under cycloplegia in children from 6 months to 3 years of age]. PMID- 2225279 TI - [Use of collagen lenses]. PMID- 2225281 TI - DNA analysis of periampullary cancers. AB - The nuclear DNA content in 71 cases of periampullary cancer (27, cancer of the head of the pancreas (Ph); 24, cancer of the ampulla of Vater (A); and 20, cancer of the inferior common bile duct (Bi] was measured cytofluorometrically using the archival paraffin-embedded specimens of the primary lesions. They were analyzed in relation to prognosis, tumor size, histological differentiation, lymph node metastasis, lymphatic invasion, venous invasion, perineural invasion, and growth pattern. The results show that "Ph" has more unfavorable prognosis compared with the other two and it has more DNA content under the same conditions such as tumor from 2.1 to 4 cm in its greatest dimension, well differentiated adenocarcinoma, with or without lymph node metastasis, with or without venous invasion, with lymphatic invasion, with perineural invasion, and in the intermediate growth pattern between expansive and infiltrative. In conclusion, this study demonstrates a close correlation between the DNA content and prognosis and the significant clinical value of DNA analysis for predicting the prognosis in patients of periampullary cancer. PMID- 2225282 TI - Comparison of arteriosclerosis obliterans of lower limbs between China and Japan. AB - Clinical data on 50 patients with arteriosclerosis obliterans (ASO) in China (Group A) and Japan (Group B) respectively were studied for better understanding of these changing trends. The results showed that the incidence of ASO peaked in Group A in the 50 to 69 age range (88%) and in Group B in the 55 to 74 age range (78%). Group A had a lower ratio of smokers and cases of diabetes mellitus than Group B but a higher ratio of hypertension and a higher total cholesterol level. Angiography showed that the prevalence of atherosclerotic lesions in the lower extremities as a whole was similar for both groups. They were different in location, extent and severity of the arteries involved between the two groups. We believe that this study has shown various differences between the two groups but that the causes are probably multifactorial. PMID- 2225283 TI - Squamous cell carcinoma antigen in oral squamous cell carcinomas. AB - Squamous cell carcinoma (SCC) antigen is a tumor-associated antigen isolated from the squamous cell carcinoma of the uterine cervix. In order to estimate the usefulness of the SCC antigen in monitoring the clinical behaviors of oral squamous cell carcinomas, we analyzed clinicopathologically and immunohistochemically 54 cases of squamous cell carcinoma of the oral cavity. Elevated serum SCC antigen levels were detected in 23 (42.6%) out of 54 oral squamous cell carcinomas. The positive rate of serum SCC antigen levels was significantly higher in the patients with advanced clinical stages and poorly differentiated carcinoma. The serum levels declined rapidly after the surgical operation. It is considered that the serum SCC antigen levels could be useful in monitoring the extension, effectiveness of therapy, recurrence and metastases of the oral squamous cell carcinomas. Immunohistochemically, strong staining was seen in the cytoplasm of the well-differentiated carcinoma cells. PMID- 2225284 TI - Ultrastructural study on effects of cisplatin on VX2 carcinoma cells. AB - The effects of intraarterial chemotherapy with cisplatin on rabbit VX2 carcinoma transplanted to the hind legs of animals were studied. Following intraarterial (IA) or intravenous (IV) administration of cisplatin (2.5 mg/kg), changes in the tumor cells were examined electron microscopically. The treated cells showed enlargement with decrease in the amount of nuclear chromatin and prominent nucleolar segregation. In many cells, the cytoplasmic organelles had migrated to the paranuclear area. The most striking change was the appearance of numerous microvilli-like cytoplasmic projections. Multinucleated giant cells were also observed. The changes were more prominent following IA cisplatin. The author concludes that significant ultrastructural changes can be demonstrated by the regional administration of cisplatin in rabbit VX2 carcinoma and that these promising results should be followed by clinical trials. PMID- 2225285 TI - Autologous blood transfusion in orthopedic and oral surgical patients. AB - The procedure for autologous blood transfusion in the orthopedic and oral surgical patients in our university hospital is described. The collection of blood was begun from 3 weeks prior to the scheduled surgery. Each time 200 or 400 ml were collected, making three collections possible. The collected blood was stored in liquid form up to the day of the operation and returned to the same patient. Without any difficulty, 600-1200 ml of blood were collected from many patients. All patients were prescribed an oral iron supplement (200 mg/day). No significant decrease in the serum iron and ferritin levels after two or three collections was observed. Eighty-nine percent of the orthopedic patients and 87% of the oral surgical patients were transfused only with autologous blood during the operation. Homologous blood transfusion was performed in the patients with more than 2,200 ml of blood loss. The autologous blood collection of 800 ml may be sufficient enough in at least 80% of these patients. PMID- 2225286 TI - Patient-controlled analgesia--does it provide more than comfort? PMID- 2225287 TI - Ropivacaine--a worthy replacement for bupivacaine? PMID- 2225288 TI - Reduction of postoperative morbidity following patient-controlled morphine. AB - The present study examined the impact of two methods of pain management on recovery in 38 women undergoing hysterectomy. One group received IV morphine in the recovery room and IM morphine on the ward on a PRN basis (PRN group). In the other group, a loading dose of morphine 8 mg IV was given when the patient first complained of pain and patient-controlled IV morphine (PCA) was initiated and continued for 48 h (PCA group). Both groups received similar amounts of morphine overall, differently distributed over time. The PCA patients received 8 mg.h-1 in the recovery room (approximately 2.5 hrs) and less thereafter. The PRN patients received approximately 2 mg.h-1 for the entire 48-hr period. Pain control was better throughout convalescence and less variable across time with PCA management. Minute ventilation also recovered faster and by day four was 25 per cent above the preoperative baseline in the PCA group. In addition, oral temperature became normal one day earlier, ambulation recovered more rapidly and patients were discharged from hospital earlier. The data suggest that early treatment with relatively high, self-titrated morphine doses may alter the course of the metabolic response to surgery. PMID- 2225289 TI - Brachial plexus block with a new local anaesthetic: 0.5 per cent ropivacaine. AB - A new local anaesthetic, ropivacaine hydrochloride, was used in a concentration of 0.5 per cent in 32 patients receiving a subclavian perivascular block for upper extremity surgery. One group (n = 15) received 0.5 per cent ropivacaine without epinephrine and a second group (n = 17) received 0.5 per cent ropivacaine with epinephrine in a concentration of 1:200,000. Anaesthesia was achieved in 87 per cent of the patients in both groups in all of the C5 through T1 brachial plexus dermatomes. Motor block was profound with 100 per cent of patients in both groups developing paresis at both the shoulder and hand and 100 per cent developing paralysis at the shoulder. There was a rapid initial onset of sensory block (a mean of less than four minutes for analgesia) with a prolonged duration (a mean of greater than 13 hr of analgesia). The addition of epinephrine did not significantly affect the quality or onset of sensory or motor block. The duration of sensory block was reduced by epinephrine at T1 for analgesia and at C7, C8, and T1 for anaesthesia. The duration of sensory block in the remaining brachial plexus dermatomes as well as the duration of motor block was not effected by epinephrine. There was no evidence of cardiovascular or central nervous system toxicity in either group with a mean dose of 2.5-2.6 mg.kg-1 ropivacaine. PMID- 2225290 TI - Neurological phenomena during emergence from enflurane or isoflurane anaesthesia. AB - During emergence from anaesthesia, transient neurological signs that would usually be considered pathological may appear. The objective of this randomized, patient (n = 30) and observer-blinded study was to compare prospectively the incidence and duration of post-anaesthetic neurological abnormalities in healthy patients undergoing minor elective procedures following thiopentone and succinylcholine induction, and enflurane-N2O or isoflurane-N2O anaesthesia. Patients were studied for 60 min after anaesthesia. Arousal state, muscle tone, deep tendon reflexes, plantar reflex, sustained clonus, shivering, intense muscular spasticity and temperature were assessed. Results of neurological examination were correlated with the patient's state of arousal. Transient emergent neurological abnormalities occurred more frequently following enflurane N2O anaesthesia than isoflurane N2O anaesthesia. This was statistically significant (P less than 0.05) for quadriceps hyperreflexia, upgoing toes (positive Babinski reflex) and intense muscular spasticity. Neurological abnormalities occurred most commonly 5-20 min after anaesthesia and all abnormalities resolved within 60 min. Following enflurane anaesthesia, as patients became more alert the incidence of abnormalities declined, while the arousal state did not affect the incidence of abnormalities after isoflurane. There was no significant difference between axillary temperatures of those patients who shivered and those who did not. In conclusion, temporary emergent neurological abnormalities occurred more often following enflurane-N2O than after isoflurane-N2O anaesthesia. PMID- 2225291 TI - Hyperkalaemia during rapid blood transfusion and hypovolaemic cardiac arrest in children. AB - A morbidity and mortality review documented a high occurrence of hyperkalaemia in cardiac arrests associated with rapid blood transfusion, which resulted in further study. In order to stimulate events during rapid blood transfusion and cardiac arrest, the central circulation was modeled as a linear one compartment, and used to stimulate a child who suffered a hypovolaemic cardiac arrest and was resuscitated with rapid blood transfusion (RBT). The simulation suggested that the combination of RBT and a low cardiac output state could be associated with hyperkalaemia, if the potassium concentration in the plasma fraction of the transfused blood was greater than or equal to 10 mmol.L-1. In an associated clinical study the plasma potassium concentration during cardiac arrest was documented from a retrospective review of 138 cardiac arrests in a paediatric population. Patients were divided into two groups. The RBT-group received a rapid blood transfusion during resuscitation. The non-RBT group did not receive blood during resuscitation. During cardiac arrest the plasma [K] in the non-RBT group was 5.63 +/- 2.39 mmol.L-1 compared with 8.23 +/- 1.99 mmol.L-1 in the RBT-group (P less than 0.05). The hyperkalaemia during cardiac arrest in the RBT-group could be explained as a consequence of RBT to a hypovolaemic child with a low cardiac output. PMID- 2225292 TI - Alfentanil controls the haemodynamic response during rapid-sequence induction of anaesthesia. AB - Laryngoscopy and tracheal intubation often cause hypertension and tachycardia, which may be exaggerated during rapid-sequence induction of anaesthesia. A placebo-controlled, double-blind study was conducted in 60 patients to determine dose-response and effects on myocardial performance of alfentanil when used to attenuate this cardiovascular response. Patients were divided into four groups to receive a pre-induction bolus from a coded syringe, which contained either normal saline (PLAC), alfentanil 30 micrograms.kg-1 (ALF 30), alfentanil 45 micrograms.kg-1 (ALF 45) or alfentanil 60 micrograms.kg-1 (ALF 60). Anaesthesia was induced in rapid sequence with thiopentone 4.0 mg.kg-1 and succinylcholine 1.5 mg.kg-1, and the trachea was intubated 60 sec later. Increases in heart rate (21 +/- 10 bpm), mean arterial pressure (28 +/- 13 mmHg), and systemic vascular resistance index (1420 +/- 780 dynes.sec-1.cm-5) were observed in response to intubation with PLAC but in none of the 3 ALF groups (P less than 0.05). However, heart rate and mean arterial pressure decreased significantly in both the ALF 45 and ALF 60 groups (P less than 0.05), whereas ALF 30 resulted in no change in these variables over time. Cardiac index, stroke volume index, and ejection fraction tended to decrease in all four groups, but none of these variables was different at corresponding time when comparing the ALF groups with PLAC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225295 TI - Continuous suprascapular nerve block for analgesia of scapular fracture. AB - Fracture of the scapular is uncommon but painful. A case is described in which a comminuted scapular fracture was treated with a continuous suprascapular nerve block. With the patient lying supine an epidural needle was directed towards the scapular notch via a superior approach and an epidural catheter was placed when the notch was believed to have been identified. Repeat injections of 10 ml bupivacaine 0.25 per cent with 1/200,000 epinephrine provided analgesia within minutes and a duration of 8-10 hr. Injection of 10 ml radio-opaque dye demonstrated the catheter to be lateral to the scapular notch. However, dye dispersed throughout the supraspinous fossa including the scapular notch thus blocking the suprascapular nerve. This case demonstrates that continuous suprascapular nerve block can be performed for five days and that location of the scapular notch is less important than previously thought. PMID- 2225293 TI - Brain protection: physiological and pharmacological considerations. Part II: The pharmacology of brain protection. AB - Neuroprotective agents may exert their effect by reducing cerebral oxygen demand (CMRO2), increasing cerebral oxygen delivery, or by altering ongoing pathological processes. Barbiturates provide neuroprotection by reducing the CMRO2 necessary for synaptic transmission while leaving the component necessary for cellular metabolism intact. Isoflurane may exert a neuroprotective effect by a similar mechanism but its efficacy is likely less than that of barbiturates due to adverse effects on cerebral blood flow. Lidocaine reduces CMRO2 by affecting both cellular metabolic processes and synaptic transmission and thus resembles hypothermia in its mechanism of action. Benzodiazepines reduce CMRO2 by reducing synaptic transmission and their use as neuroprotectants produces less haemodynamic compromise than barbiturates. The mechanism of protection by calcium entry blocking agents appears to be due to improved blood flow as opposed to altering abnormal Ca++ fluxes. In contrast, agents such as ketamine and MK-801 may prevent abnormal Ca++ fluxes through their competitive interaction with N methyl-D-aspartate receptors. Phenytoin prevents K(+)-mediated ischaemic events from progressing. Agents worthy of further investigation include corticosteroids, free radical scavengers, prostaglandin inhibitors and iron chelators. PMID- 2225296 TI - Epidural catheter migration during labour: an hypothesis for inadequate analgesia. AB - The purpose of this study was to determine the incidence and factors associated with poor analgesia during epidural block for labour pain. Emphasis was placed on determining the incidence, magnitude and factors associated with epidural catheter migration as well as any relationship between catheter migration and the quality of analgesia. Catheter movement was assessed, prospectively, in 211 consecutive parturients who had an epidural catheter placed for labour analgesia. The magnitude and direction of catheter movement was assessed by measurement of the length of the catheter at the skin at the time of epidural placement, and immediately before removal of the catheter, after delivery. Fifty-four per cent of the catheters migrated during labour and 70 per cent of these migrated out of the epidural space. The quality of analgesia provided by the epidural block was assessed by the caseroom nurse caring for the patient. Seventeen per cent of the patients had unsatisfactory analgesia. There was an increase in poor analgesia in those patients whose catheters migrated compared with those in whom the catheters were stable (P less than 0.05). We conclude that catheter migration during labour results in a greater incidence of inadequate block and unsatisfactory analgesia. PMID- 2225294 TI - Anaesthesia for renal transplantation in sickle cell disease. AB - Sickle cell disease (SCD) is associated with many pathological and functional abnormalities affecting all organ systems. Renal manifestations of SCD may result in end-stage renal disease (ESRD), which can be treated by chronic haemodialysis or renal transplantation. Renal transplantation was successfully performed in a 25-yr-old male with sickle cell beta-thalassaemia and nephrotic syndrome. We present a case report of this patient, a discussion of the renal complications associated with SCD and the perioperative management of a patient with SCD undergoing renal transplantation. PMID- 2225297 TI - Side effects of nalbuphine while reversing opioid-induced respiratory depression: report of four cases. AB - Nalbuphine hydrochloride, an agonist-antagonist opioid, is reported to reverse the respiratory depression of moderate doses of fentanyl (20 micrograms.kg-1) and still provide good analgesia. We report four patients having abdominal aortic aneurysm repair in which we attempted to reverse the respiratory depression of large doses of fentanyl (50-75 micrograms.kg-1) with nalbuphine (0.3 mg.kg-1, 0.1 mg.kg-1 or 0.05 mg.kg-1). Nalbuphine reversed respiratory depression in all four patients and the respiratory rate increased from 10 to 23 breaths per minute, end tidal CO2 decreased from 7.0 +/- 0.3 per cent to 5.6 +/- 0.7 per cent, and peak inspiratory pressure after 0.1 seconds increased from 4 +/- 1.4 to 13 +/- 2.6 mmHg. However, hypertension, increased heart rate, and significant increase in analogue pain scores accompanied reversal of respiratory depression. Agitation, nausea, vomiting, and cardiac dysrhythmias also were observed frequently. We do not recommend the use of nalbuphine to facilitate early extubation of the trachea after large doses of fentanyl for abdominal aortic surgery. PMID- 2225298 TI - The prophylactic use of octreotide in a patient with ovarian carcinoid and valvular heart disease. AB - This case report describes the use of octreotide, a long-acting somatostatin analogue, in the management of a patient with an ovarian carcinoid tumour and severe cardiac valvular disease. This patient underwent laparotomy and tumour resection without complication. Anaesthesia was induced with midazolam, fentanyl, and vecuronium, and maintained with isoflurane as well as additional fentanyl and vecuronium. However, we feel that it was the use of octreotide that prevented a life-threatening crisis intraoperatively, and recommend its use in patients with carcinoid syndrome undergoing anaesthesia and surgery. PMID- 2225300 TI - Vertigo after epidural morphine. AB - Severe complications from the use of epidural morphine for analgesia after Caesarean section are rare. A case is reported of extreme prostrating vertigo several hours after epidural morphine injection, where the time of onset of the symptom coincided with the expected time of arrival of the morphine within intra cerebral cerebro-spinal fluid. PMID- 2225299 TI - Elevated serum bromide concentrations following repeated halothane anaesthesia in a child. AB - A 20-month-old child received 25 brief halothane general anaesthetics over a five week period to allow cranial irradiation treatments for a posterior fossa ependymoma. Personality change during the last week of the treatment protocol raised the question of possible bromide intoxication. Serum bromide concentrations, using a gold chloride assay technique, were monitored at that time, and at four- and six-week intervals thereafter. Serum bromide concentrations demonstrated a four-fold change during this period ranging from peak levels of 2.2 mEq.L-1 (176 micrograms.kg-1) during the fifth week of treatment decreasing to less than 0.5 mEq.L-1 (less than 40 micrograms.ml-1) six weeks following the end of treatments. This demonstrates the possibility for repetitive, short halothane exposures to result in elevations of serum bromide and the potential of bromide intoxication in paediatric neuro-oncology patients. PMID- 2225301 TI - Anaesthetic management of the brain dead for organ donation. AB - An increasing number of anaesthetists is being called upon to manage organ donors during organ retrieval procedures. We briefly describe the technical aspects of the surgical procedure together with a guide to the anaesthetic management. The aims of the latter may be summarized as the "Rule of 100": systolic blood pressure greater than 100 mmHg, urine output greater than 100 ml.hr-1, PaO2 greater than 100 mmHg, haemoglobin concentration greater than 100 g.L-1. Common management problems (hypotension, arrhythmias, diabetes insipidus, oliguria, and coagulopathy) are discussed in detail. The intraoperative management of the brain dead organ donor provides the anaesthetist with the challenge of a major surgical procedure in a subject with important physiological derangements. PMID- 2225302 TI - Thoracic epidural anaesthesia combined with enflurane anaesthesia reduces atrioventricular conduction in dogs. AB - Cardiac electrophysiological variables during thoracic epidural lidocaine (TEL) were compared with those during continuous intravenous lidocaine (IVL) infusion in 14 mongrel dogs anaesthetized with enflurane in order to investigate the combined effects of thoracic epidural anaesthesia (TEA) and enflurane anaesthesia on intracardiac conduction. Thoracic epidural lidocaine suppressed intracardiac conduction. Sinus cycle length (SCL) and Atrium-His (AH) interval increased by 9 and 11 per cent respectively (P less than 0.05), 30 min after TEL. Intravenous lidocaine did not increase either SCL or AH. The functional refractory period of the atrioventricular node increased five per cent above the control value 15 min after TEL (P less than 0.05), while it was unchanged in the IVL group. The mean plasma concentrations of lidocaine ranged from 0.48 +/- 0.07 to 1.00 +/- 0.14 micrograms.ml-1 in the TEL group and from 0.98 +/- 0.13) to 1.21 +/- 0.15 micrograms.ml-1 in the IVL group. There were no significant differences in plasma concentrations of lidocaine in both groups during the observation period. Therefore, it is concluded that the depressant effects of TEA on intracardiac conduction were caused by blocking of the sympathetic efferent activity. Caution may be advised in administering TEA when cardiac conduction is already compromised. PMID- 2225303 TI - Bupivacaine-induced slow-inward current inhibition: a voltage clamp study on frog atrial fibres. AB - The effects of various concentrations of bupivacaine on the characteristics of the slow-inward current (isi) were studied over a ten-minute period on isolated frog atria. At a concentration of 10(-7) M, bupivacaine did not modify isi. At 10(-6) M, the maximal amplitude of the slow-inward current (i max) was depressed by 11 per cent. At 10(-5) M, i max was depressed by 24.5 per cent, the time-to peak current value (tpeak) was increased by 13.4 per cent and the inactivation time constant (tau in) by 29.8 per cent. At 10(-4) M, i max was depressed by 32.9 per cent, tpeak increased by 30.4 per cent and tau in by 58.7 per cent. In conclusion, bupivacaine produced only moderate inhibition of the slow-inward current. The findings might explain the decline in sinus impulse formation with sinus bradycardia, and the slowing of atrio-ventricular node conduction produced by bupivacaine. However, the decrease in contractility previously reported does not seem to be due only to inhibition of the slow-inward current. PMID- 2225304 TI - A simple technique for topical anaesthesia of the airway. PMID- 2225306 TI - Obstruction of a preformed armoured tracheostomy tube. PMID- 2225305 TI - Venous tolerance to etomidate in lipid emulsion or propylene glycol (hypnomidate) PMID- 2225309 TI - A new syringe holder. PMID- 2225308 TI - Acute pulmonary oedema after tourniquet release. PMID- 2225307 TI - Fatal air embolism. PMID- 2225312 TI - Comparison of acute effects of anthracyclines on cardiac electrophysiological parameters of isolated guinea-pig hearts. AB - This study was performed to evaluate the acute effects of two anthracycline derivatives, doxorubicin and 4'O-tetrahydropyranyl-doxorubicin [(THP) doxorubicin], on the conduction intervals, heart rate and refractoriness of isolated spontaneously beating guinea-pig hearts using a high-resolution ECG recording technique (SST-ECG). Doxorubicin as well as (THP)-doxorubicin were added to the perfusate in increasing concentrations of 0.1, 1 and 10 microM. Doxorubicin did not significantly alter the heart rate or conduction intervals. Only the rate-dependent QT interval was significantly shortened under the influence of 10 microM doxorubicin. In contrast, 10 microM (THP)-doxorubicin led to a significant reduction in the heart rate (-13% +/- 3%; P less than 0.01, n = 7) and to a prolongation of atrioventricular conduction time (24% +/- 10%; P less than 0.05, n = 7). The rate-dependent repolarization period (QT interval) was only insignificantly shortened in the presence of 10 microM (THP)-doxorubicin. The maximal following frequencies of each part of the conduction system were not changed by 10 microM doxorubicin. In the presence of (THP)-doxorubicin, the maximal following frequency of the ventricular myocardium was increased by as much as 36% +/- 8% (P less than 0.01, n = 7), indicating a shortening of the effective refractory period of the ventricular myocardium (V-ERP). These results show that the activation of (THP)-doxorubicin resembles the effects of Ca antagonistic compounds on the heart (i.e. decrease in the spontaneous sinus rate and prolongation of the AV-nodal conduction interval). Changes in the QT interval exerted by doxorubicin and the shortening of the ventricular effective refractory period by (THP)-doxorubicin may indicate an alteration of the K(+)-conductance of the membrane. As the acute electrophysiological effects of doxorubicin and (THP) doxorubicin are modest and occur only at excessive concentrations (10 microM), a direct influence on the generation of arrhythmias in healthy hearts is unlikely. PMID- 2225313 TI - Clinical pharmacokinetics of intravenously injected tritiated vinzolidine. AB - Vinzolidine (VZL), a novel, semi-synthetic vinca alkaloid showing evidence of oncolytic activity in phase I/II clinical trials, was studied in six patients for its pharmacokinetic and metabolic behavior. Following i.v. administration of [3H] VZL at doses of 5, 6.7, and 9 mg/m2, blood and urine samples were collected and analyzed by sample oxidation and HPLC. Following a single i.v. dose, decay of total tritium in plasma was tetraphasic, with a rapid initial t1/2 alpha of 0.044 +/- 0.013 h, followed by a t1/2 beta of 0.54 +/- 0.22 h and a t1/2 gamma of 9.48 +/- 4.89 h; the terminal t1/2 gamma was 219 +/- 57 h. The mean plasma clearance of total tritium was 0.054 +/- 0.044 l.kg/h, and the mean volume of distribution was 14.3 +/- 5.4 l/kg; mean urinary excretion was 13.6% +/- 4.3% of the delivered radioactivity. Qualitative analysis of plasma and urine revealed the predominance of unchanged VZL plus two unidentified metabolites with different elution times. In comparison with oral VZL, as previously reported, i.v. injected VZL showed comparable values with respect to the volume of the central compartment (VC), plasma clearance (Clp), and terminal t1/2 for total tritium. Qualitatively, the metabolites observed in plasma and urine were comparable in number and quantity with values obtained in analyses after oral administration. PMID- 2225310 TI - Cellular glutathione as a protective agent against 4-hydroperoxycyclophosphamide cytotoxicity in K-562 cells. AB - Exposure of cells of the K-562 erythroleukemia cell line to 4 hydroperoxycyclophosphamide (4-HC), an analog of activated cyclophosphamide, causes a concentration-dependent inhibition of in vitro colony formation by these cells. For investigation of the role of glutathione (GSH) in the metabolism of 4 HC, GSH levels of K-562 cells were modulated by exposing the cells to buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, and/or to GSH ethyl esters. Both the mono- and diethyl esters of GSH were synthesized in our laboratories and their identities were determined by chromatographic methods and fast-atom-bombardment mass spectrometry. An HPLC method including electrochemical detection used for thiol determination was applied for the measurement of GSH esters. Incubation of the cells with BSO depleted GSH levels to approximately 11% of control values and potentiated the cytotoxicity of 4-HC. By contrast, exposure to GSH esters approximately doubled GSH levels and protected the cells against the toxicity of 4-HC. Moreover, when cellular GSH levels were first depleted by BSO exposure and then replenished by incubation with GSH esters, the BSO associated potentiation of 4-HC cytotoxicity was abolished. The work described herein extends the application of an HPLC method used for thiol determination to the measurement of GSH ethyl esters. In addition, it established that GSH acts as a competitive protecting agent against the in vitro toxicity of 4-HC in the K-562 cell line. PMID- 2225311 TI - Pharmacokinetics of the recombinant fusion protein DAB486IL-2 in animal models. AB - The kinetics of the in vitro cytotoxicity of DAB486IL-2, a genetically engineered fusion protein containing a portion of diphtheria toxin and human interleukin-2, were examined in the C91/PL cell line, which constitutively expresses IL-2 receptors. Maximal inhibition of protein synthesis was observed by 4-6 h after DAB486IL-2 addition at a concentration of 300 ng/ml. The tissue distribution, urinary excretion, and plasma pharmacokinetics of DAB486IL-2 in the rat and its plasma pharmacokinetics in the monkey were also examined. In rats the primary site of distribution of [35S]-DAB486IL-2 outside the vasculature appears to be the liver, followed by the kidney, spleen, and lung. Persistence of radioactive material in the liver and urinary excretion of metabolic degradation products suggest that labeled protein is metabolized by hepatic tissue. Following i.v. bolus administration of DAB486IL-2, the initial serum half-life for both the rat and the monkey was approximately 5 min. The overall clearance rate of drug for the two species differed, with DAB486IL-2 being cleared from circulation 2-3 times more rapidly in the monkey. Presence of high levels of neutralizing antibodies to diphtheria toxin in the rat significantly influenced the clearance of bioactive DAB486IL-2. However, the question as to whether the presence of in vitro biological activity for the molecule is masked by the presence of antibodies cannot be clearly answered. PMID- 2225314 TI - Characterisation of urinary metabolites of temozolomide in humans and mice and evaluation of their cytotoxicity. AB - The experimental antineoplastic agent temozolomide was not metabolised in vitro at a measurable rate by mouse liver fractions. In contrast, the temozolomide analogue 3-methylbenzotriazinone was metabolically N-demethylated by hepatic microsomes to yield benzotriazinone. The major route of excretion of [14C] labelled temozolomide in mice was via the kidneys. An acidic metabolite of temozolomide, probably a conjugate, was found in the urine of mice, but its identity could not be established unambiguously. Spectroscopic analysis and chemical tests revealed that it possesses an intact NNN-linkage. Another metabolite was found in the urine of patients but not of mice. This metabolite was identified as the 8-carboxylic acid derivative of temozolomide. Unlike the unknown species, this metabolite was cytotoxic against TLX5 lymphoma cells in vitro. PMID- 2225315 TI - Cross-resistance pattern of cell lines selected for resistance towards different cytotoxic drugs to membrane-toxic phospholipids in vitro. AB - The synthetic ether lipids ET-18-OCH3 and BM41.440 and a derivative, hexadecylphosphocholine, were tested for inhibition of [3H]-thymidine uptake into a Chinese hamster ovarian cell line (AUXBl) and its multidrug-resistant subline selected for colchicine resistance (CHRC5). The activity of all three compounds against the multidrug-resistant subline was equal to or higher than that against the parent line. The same result was found for their activity against a human leukemic lymphoblastic cell line (CEM/O) and its methotrexate-resistant subline (CEM/MTX). In contrast, two multidrug-resistant cell lines selected for resistance to Adriamycin, the mouse leukemia cell line P388/ADR and the murine sarcoma cell line S180/ADR, expressed modest cross-resistance to the lipids as measured by thymidine uptake. Experiments performed using the trypan-blue dye exclusion assay yielded comparable results, although this system revealed a slightly different sensitivity in showing the cytotoxicity of the drugs. By this assay, modest cross-resistance for ET-18-OCH3 and BM41.440 to Adriamycin was found only after 24 h incubation and decreased after 48 h incubation, with almost equal sensitivity to both drugs being shown by the parental (P388/W) and resistant lines (P388/ADR). Furthermore, findings from a human tumor-cloning assay were in accordance with these data, although they did not indicate cross resistance for the P388/ADR cell line. These results suggest that certain ether lipids and derivatives might represent valuable anticancer drugs warranting further study in the setting of resistant disease. PMID- 2225316 TI - The influence of partial hepatectomy on the pharmacokinetics of preoperatively injected 4'-epidoxorubicin in rats. AB - Preoperative administration of 4'-epidoxorubicin (Epi-A) has been suggested as adjuvant therapy in patients undergoing liver resection for hepatocarcinoma. To assess the influence of partial hepatectomy on the pharmacokinetics of Epi-A, an experimental study in rats was undertaken in which 5 mg/kg Epi-A was given i.v. 10 min prior to a 2/3 hepatic resection or sham operation. Epi-A levels in liver tissue and plasma were determined using a sensitive and specific HPLC method. A marked uptake of Epi-A in liver tissue was found at 10 min after injection. The partially hepatectomized rats showed a 2-fold increase in AUC between 4 and 72 h as compared with the sham-operated controls. The terminal half-life from 24 to 72 h was not significantly changed by the partial hepatectomy. The plasma binding of Epi-A was measured at 4 h post-surgery. The fraction of unbound Epi-A was 0.16 in partially hepatectomized animals and 0.20 in sham-operated rats. The results indicate that when Epi-A is given prior to liver resection, a dose reduction might be necessary to avoid increased side effects due to the rise in AUC. PMID- 2225317 TI - Weekly fluorouracil and high-dose leucovorin: efficacy and treatment of cutaneous toxicity. AB - Intensive therapy with 5-fluorouracil (FU) and leucovorin (LV) has proved to be effective in the treatment of advanced colorectal cancer. The toxicity of this regimen has not been systematically evaluated. In the present study, 52 patients with advanced colorectal and refractory cancers received sequential 2-month cycles of weekly FU and high-dose LV and were monitored for toxicity as well as response in 103 cycles. Of 24 evaluable patients with colorectal cancer, 1 complete and 9 partial responses were seen (42%); 4 of 10 patients who had been refractory to conventional FU treatment responded to the FU/LV regimen. One partial response was observed among six patients with gastric carcinoma, and three minor responses were seen in five women with refractory breast cancer. A total of 24 patients (46%) completed the first cycle on schedule, although 7 subjects required a reduction in the dose of FU. The majority of patients required treatment breaks because of toxicity. Gastrointestinal toxicity proved to be dose-limiting on this schedule, necessitating FU dose modification and treatment of both diarrhea in 15 subjects and acute abdominal pain in 7 cases. No patient required a further treatment delay of FU dose adjustment. Myelosuppression was an uncommon complication on this regimen. Cutaneous toxicity was also prominent in this series of patients, with the hand-foot syndrome developing in 14 cases (27%); 11 subjects who developed this complication were treated with pyridoxine (150 mg daily), and all experienced improvement in their symptoms within 1 week. Partial and complete responses were observed in 41% of evaluable patients with colorectal cancer and in one of six evaluable patients with gastric carcinoma. We conclude that FU and high-dose LV can safely be given on a weekly basis, although acute gastrointestinal and cutaneous toxicity are common. PMID- 2225319 TI - Renal effects of S10036 in man. AB - The renal hemodynamic and tubular effects of S10036 (fotemustine) were evaluated in seven patients with advanced malignancy. Initial evaluation carried out prior to treatment and repeated 1 day after the first fotemustine infusion and 7 days after the second included clinical, haematological parameters, liver-function tests, and determination of the glomerular filtration rate, renal blood flow and enzymuria. The glomerular filtration rate was 108 +/- 3.7 ml/min before treatment and remained stable after the first (117 +/- 5 ml/min) and second (124 +/- 6 ml/min) fotemustine infusions. Renal blood flow and urinary beta 2-microglobulin and N'-acetylglucosaminidase excretion were also not modified by fotemustine administration. We conclude that fotemustine does not acutely alter renal haemodynamics, nor does it have direct tubular toxicity. PMID- 2225318 TI - Phase II trial of carboplatin and vinblastine in advanced squamous-cell carcinoma of the head and neck. AB - A chemotherapy regimen consisting of carboplatin and vinblastine was given to 30 patients with recurrent or previously untreated, locally advanced squamous carcinoma of the head and neck region. The main aim of the study was to assess the toxicity of this regimen, the feasibility of its outpatient administration and the tumour response. A total of ten patients (33%) achieved an objective response, including two who achieved a complete response. The combination offered useful palliation for patients with recurrent disease; it was well tolerated and can be given on an outpatient basis. This regimen could be combined with other active agents such as methotrexate or bleomycin. PMID- 2225320 TI - Peroxisome proliferation and modulation of rat liver carcinogenesis by 2,4 dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, perfluorooctanoic acid and nafenopin. AB - Using an initiation--selection--promotion protocol for induction of liver tumors in Wistar rats, the modulating action of various peroxisome proliferators on neoplasia as well as on selected biochemical parameters was studied. After treatment with diethylnitrosamine (DEN), the animals were subsequently subjected to a selection procedure involving feeding of 2-acetylaminofluorene (2-AAF), and in the middle of the 2-AAF treatment, a single necrogenic dose of carbon tetrachloride. Following a recovery period, the rats were fed a diet containing 0.1% nafenopin (NAF), 0.015% perfluorooctanoic acid (PFOA), 0.05% 2,4 dichlorophenoxyacetic acid (2,4-D), 0.05% 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) or 0.05% phenobarbital (PB) as a positive control. When the animals were killed, 7 months after initiation, the incidence of hepatocellular carcinoma was 83, 33 and 16% in the animals treated with NAF, PFOA or 2,4,5-T respectively. No cancers were observed in controls, or in the 2,4,-D groups. In comparison with controls, NAF and PFOA caused a 60-and 24-fold increase inthe peroxisomal beta oxidation of fatty acids respectively, but only about a 2-fold increase in the catalase activity, 2,4-D and/or 2,4,5-T were much less active in this respect, giving approximately a doubling in the rate of fatty acid oxidation. The specific activity of D-amino acid and glycolate oxidases were significantly depressed, whereas the urate oxidase levels were apparently unaffected by the NAF and PFOA treatment. The results suggest that the selective induction of peroxisomal fatty acid oxidation is consistent with the hypothesis that imbalance between H2O2 overproduction and its destruction could play a role in the modulation of hepatocarcinogenesis by peroxisome proliferators. PMID- 2225321 TI - Serological characterization of polycyclic aromatic hydrocarbon diolepoxide-DNA adducts using monoclonal antibodies. AB - Polycyclic aromatic hydrocarbons (PAHs) are a group of structurally related compounds that are present in the environment in complex mixtures as common pollutants. These compounds have been studied extensively because of their carcinogenic and toxic properties to humans. We reported previously that humans exposed to certain PAHs produce antibodies that bind to different PAH diolepoxide DNA (PAH-DNA) adducts. The ability to detect and measure antibodies to PAH-DNA adducts in human blood samples could prove useful as a biological dosimeter for identifying persons that have been exposed to high levels of PAHs, i.e. persons who may be at high cancer risk. In our initial studies we found that it was common for persons who were exposed to PAH to produce antibodies against PAH-DNA adducts. However, we were unable to identify the actual chemical types of PAH-DNA adducts that were recognized by the serum antibodies because many serum samples contained antibody activity to more than one adduct. These data indicate that different PAH-DNA adducts may be serologically similar or that humans actually produce immune responses against more than a single PAH-DNA adduct. We have used monoclonal antibody technology to determine the extent to which different PAH-DNA adducts share serologically recognized epitopes. Monoclonal antibodies were produced against two different PAH-DNA adducts, benzo[a]pyrene diolepoxide-DNA (BPDE-DNA) and benz[a]anthracene diolepoxide-DNA (BADE-DNA). The binding of these antibodies to five PAH-DNA adduct preparations and to soluble PAHs was assessed. We found that most monoclonal antibodies bound to more than a single type of PAH DNA adduct, documenting the serological relatedness of different PAH-DNA adducts. However, two monoclonal antibodies were produced that bound only to BPDE-DNA. Soluble non-metabolized PAHs and PAH tetraols were not recognized by these antibodies, thus demonstrating their specificity for PAH-DNA adducts and not the PAHs alone. Monoclonal antibodies produced against BADE-DNA also bound to chrysene diolepoxide-DNA but not to BPDE-DNA or to two other PAH-DNA adducts. These data demonstrate that significant serological cross-reactivity exists between different PAH-DNA adducts and support our contention that human antibodies to PAH-DNA can often bind to more than a single type of PAH-DNA adduct. However, our ability to produce monoclonal antibodies with restricted specificity suggest that the production of highly monoclonal antibody reagents for use in assays designed to measure PAH-DNA adducts in biological samples is feasible. PMID- 2225322 TI - Sex differences in the dietary modulation of pancreatic cancer in Syrian hamsters treated continuously with N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine. AB - The effect of continuous week-long administration of N-nitroso(2-hydroxypropyl)(2 oxopropyl)amine (HPOP) by s.c. implanted osmotic pumps was examined in male and female Syrian hamsters given access to three isocaloric synthetic diets containing 10 (LP), 20 (MP) and 30% (HP) casein respectively. At a total dose of 210 mg/kg, toxicity of HPOP, expressed as acute liver injury, was greater in male than in female hamsters. Such toxicity increased with protein intake in male, but not in female animals. Twenty-five weeks after initiation, female and male hamsters developed pancreatic ductal adenocarcinomas and to a lesser degree liver cholangiocellular and hepatocellular carcinomas. The highest incidence of pancreatic cancer was observed under HP diet regimens and was 75 and 67% in female and male hamsters respectively. Decrease of protein intake resulted in the reduction of the incidence of pancreatic cancer, which was more striking in males than in females. In males fed the MP and LP diets respectively, such an incidence declined to 33 and 6%. Although significant differences in the incidence of pancreatic cancer were not observed among female groups fed the above three diets, the multiplicity and the number of such tumors were significantly greater at the HP than the LP level. Differences in the incidence of pancreatic tumors between males and females were statistically significant only at the LP level. However, such differences were also significant at the MP level when comparisons were based on tumor number and multiplicity. Since the incidence, tumor multiplicity and size were generally greater in female than male hamsters, estrogenic hormones may play a role in the development of pancreatic ductal adenocarcinomas in this species. PMID- 2225323 TI - The initiator tRNA acceptance assay as a short-term test for carcinogens. 6. Results with 78 polycyclic aromatic compounds. AB - A total of 78 polycyclic aromatic compounds (PAH), including pure hydrocarbons, PAH metabolites, aromatic amines and nitroarenes, were tested in the initiator tRNA acceptance assay (tR assay) for carcinogens. Among the pure hydrocarbons, all strong carcinogens were highly active in the tR assay. Some weak carcinogens showed moderate positive responses, others as well as all possible non carcinogens were inactive. Various PAH metabolites, including phenols, dihydrodiols, arene oxides, dihydrodiol epoxides, quinones and benzylic sulfate esters, were positive as well. Strikingly, however, their effects rarely reached the levels observed with the strong carcinogens among the pure hydrocarbons. Moreover, the correlation with carcinogenicity was less clear, partially due to limitations in the available carcinogenicity data. The activities in the tR assay were also compared with the mutagenicity in Salmonella typhimurium. No appreciable correlation was observed. For example, trans-9,10-dihydroxy-9,10 dihydrobenzo[c]chrysene, in the absence of a mammalian metabolic system, was highly active in the tR assay, but non-mutagenic. Upon addition of rat liver enzymes, the reverse result was obtained. syn-Benzo[c]chrysene-9,10-dihydrodiol 11,12-oxide, on the other hand, was a potent direct mutagen, but required the presence of liver microsomes for a positive response in the tR assay. Thus, the metabolic basis for these two activities is different, and not yet understood for the tR assay. The partial correlations in the tR assay and in the Salmonella mutagenicity assay with carcinogenicity, and the pronounced discrepancies between these in vitro tests, may suggest that they detect different mechanisms involved in carcinogenicity. However, the tR assay was less predictive for the carcinogenicity of PAHs as compared to the previously investigated N-nitroso compounds and mycotoxins. PMID- 2225324 TI - Effects of steroids on the synthesis and metabolism of phosphatidylethanol in phorbol ester-activated lymphocytes. AB - The phorbol ester 12-O-tetradecanoylphorbol-13-acetate activates the phospholipase D pathway in bovine lymphocytes, leading to a synthesis of phosphatidylethanol (PEt) from exogenous alcohol. Concomitant treatment of the cells with 10(-8) M etiocholanolone, dehydroepiandrosterone or 16 alpha-bromo epiandrosterone results in the production of phosphatidylethanols that carry metabolically altered forms of arachidonic acid at position 2. The observed steroid response appears to be mediated by a receptor mechanism in that it depends on the synthesis of new RNA and protein. The spectrum of steroids producing the response suggests that the postulated receptor system may be distinct from the well-studied glucocorticoid, progesterone, estrogen and androgen specific receptors. The possible relevance of these new metabolites of ethanol to the problem of alcoholism in humans and to the field of carcinogenesis in general is discussed. PMID- 2225326 TI - Uptake and biological transformation of beta NiS and alpha Ni3S2 by human embryonic pulmonary epithelial cells (L132) in culture. AB - The cytotoxicity, biological transformation and interaction with plasma membranes of alpha Ni3S2 and beta NiS were studied on human embryonic pulmonary epithelial cells (L132 cell line) in culture. By establishing growth curves and survival curves, it was found that at equal molarity beta NiS has a higher inhibitory effect on cell growth than alpha Ni3S2 but a lower cytotoxic effect: the CL50 being 60 and 40 mumols/l respectively. As to their uptake, beta NiS crystals are preferentially phagocytized in their original form and then probably dissolved in the vacuoles, whereas alpha Ni3S2 is transformed in the extracellular space and in the phagocytic vacuoles into minute particles (10 nm) that are recovered bound to the cell membrane, phagocytic vacuoles and lysosomal membranes respectively. Energy dispersive spectrometry revealed that the particles bound to cell membranes no longer contain sulfur but only phosphorus and nickel as inorganic compounds. This observation suggests the formation of a Ni/P complex with the phosphate groups of membranous phospholipids and/or phosphotransferring proteins. The steady-state fluorescence polarization analysis, however, revealed a significant increase of membrane fluidity either induced by desaturation of aliphatic chains or directly by the cleavage of the fatty acid chains. These results clearly show a difference between beta NiS and alpha Ni3S2 concerning their cytotoxic effects, uptake, biological transformation and interaction with cell membranes. PMID- 2225325 TI - Differential effects on cell killing in metallothionein overexpressing CHO mutant cell lines. AB - An increased level of metallothionein (MT) within the cytosol has been associated with the development of resistance to the cytotoxic effects of alkylating agents, but the mechanism of this effect is unclear. To verify the possible role of MT as a direct scavenger of alkylating agents we transfected two alkylating agent sensitive CHO mutant cell lines, methyl methanesulphate-1 and -2 (MMS-1 and MMS 2), with the human metallothionein II-A (hMTII-A) gene. From each mutant two transfected cell clones were isolated which were found to bear episomally 50 to 70 copies of the plasmid pMTII-BPV coding for the hMTII-A gene. The transfected cell lines contained between 1.4 and 4.9 micrograms of MT per 10(7) cells. This could be increased 2- to 9-fold by heavy metal induction. Transfectants derived from mutant MMS-1 were equally sensitive as the parental cells to a set of alkylating agents. However, transfectants derived from mutant cell line MMS-2 gained significant resistance to both N-methyl-N'-nitro-N-nitrosoguanidine and N nitroso-N-methylurea, whilst retaining sensitivity to MMS. The degree of resistance was not increased by MT induction after heavy metal ion exposure. These results indicate that although resistance to alkylating agents may be mediated by a process which involves MT expression, this is not due to simple scavenging of the cytotoxic agent by the MT protein. PMID- 2225327 TI - The biochemical basis for the species difference in hepatic microsomal 4 vinylcyclohexene epoxidation between female mice and rats. AB - Mice but not rats are susceptible to 4-vinylcyclohexene (VCH)-induced ovarian toxicity and carcinogenicity. This is due in part to a 4- to 6-fold greater rate of hepatic microsomal bioactivation of VCH to the ovotoxicant VCH-1,2-epoxide. The biochemical basis for this difference was investigated in microsomes using enzyme induction, enzyme inhibition with chloramphenicol or specific inhibitory antibodies, and correlation with marker steroid hydroxylase activities to associate VCH epoxidation with particular cytochrome P450 forms. Testosterone 6 beta- and 15 alpha-hydroxylase activities and VCH epoxidation were decreased in microsomes from chloramphenicol-treated mice, initially suggesting the possible involvement of P450IIIA and P450IIA forms in VCH metabolism. Although both testosterone 6 beta-hydroxylase and VCH epoxidase activities were increased by dexamethasone treatment (P450IIIA inducer), anti-rat P450IIIA IgG inhibited testosterone 6 beta-hydroxylase (68%) but not VCH epoxidase activity. These latter results do not support the involvement of mouse P450IIIA forms in VCH epoxidation. However, results were obtained which indicated that mouse P450IIA forms are involved in VCH epoxidation. In microsomes from untreated female mice VCH epoxidase activity was inhibited 48% by antibodies to mouse P45015 alpha (P450IIA3) at a concentration that inhibited testosterone 15 alpha-hydroxylase activity by 86%. No protein immunochemically related to mouse P45015 alpha was detected in female rat hepatic microsomes. VCH epoxidation by hepatic microsomes was increased in female mice and rats by phenobarbital treatment and was inhibited by approximately one-third by anti-rat-P450IIB1 IgG in microsomes from untreated animals of both species. Furthermore, microsomal VCH epoxidase and testosterone 16 alpha-hydroxylase activities were lower (34%) in female 129/J mice (deficient in constitutive expression of P450IIB forms) than in B6C3F1 mice. These results suggested partial involvement of P450IIB forms in the microsomal epoxidation of VCH. Therefore, P450 forms IIA and IIB account for the majority of VCH bioactivation in female mouse liver, which explains in part the susceptibility of mice to VCH-induced ovarian toxicity and carcinogenicity. PMID- 2225328 TI - Fluorine probes for investigating the mechanism of activation of indeno[1,2,3 cd]pyrene to a tumorigenic agent. AB - Indeno[1,2,3-cd]pyrene (IP) is a non-alternant polycyclic aromatic hydrocarbon that has tumor-initiating activity on mouse skin and is carcinogenic in newborn mice and in rat lungs. Previous studies have shown that 8- and 9-hydroxyIP and IP 1,2-diol are major metabolites formed in vivo in mouse skin. 8-HydroxyIP-1,2-diol and 9-hydroxyIP-1,2-diol are also observed as in vivo metabolites of IP. Although 8-hydroxyIP had marginal tumor-initiating activity on mouse skin, IP-1,2-diol and its epoxide precursor, IP-1,2-oxide, had similar tumorigenic activity as IP. In the present study fluorine probes have been employed to investigate the contribution of metabolic activation at the 1,2 and 7-10 positions of IP. At a total initiating dose of 4.0 mumol, 2-fluoroIP induced skin tumors in 76% of the treated animals with an average of 3.9 tumors/mouse. At the same dose, IP induced a 72% incidence of tumor-bearing mice with 2.1 tumors/mouse. In contrast, 8,9 difluoroIP elicited a tumorigenic response in 40% of the treated animals with 0.6 tumors/animal. Five mice from each experimental group were killed at the conclusion of the initiation phase of the bioassay and DNA was isolated from the treated areas of skin. 32P-Postlabeling analysis of the hydrolyzed DNA indicated that IP forms one major detectable DNA adduct that migrates close to the origin. This adduct is absent in mice treated with 8,9-difluoroIP. In contrast, 2 fluoroIP forms one major adduct spot with different retention behavior as compared with the adduct formed from IP. DNA from mice treated topically with IP 1,2-diol and IP-1,2-oxide was subjected to 32P-postlabeling analysis. IP-1,2-diol forms one major DNA adduct spot with mobility similar to that observed for the IP DNA adduct. IP-1,2-oxide displayed an intense pattern of DNA adducts centered around the location of the IP-DNA adduct. No adducts were detected which had mobility similar to that formed from 2-fluoroIP. These results are consistent with IP undergoing metabolic activation at positions 7-10 either alone or in conjunction with dihydrodiol formation at the 1,2 position. PMID- 2225329 TI - Enhancing effects of various gastric carcinogens on development of pepsinogen altered pyloric glands in rats. AB - To assess the possibility of establishing an in vivo, medium-term bioassay system for gastric carcinogens and promoters, a total of 220 male WKY rats were divided into two groups. Group 1 animals were treated first with a single dose of N methyl-N'-nitro-N-nitrosoguanidine (MNNG) (160 mg/kg body wt) and starting 2 weeks later administrated one of five gastric carcinogens, a gastric promoter, one of five non-gastric carcinogens or no treatment, as a control, for 14 weeks. Saturated sodium chloride solution (1 ml) treatments were given by gastric intubation at weeks 4, 6, 8 and 10. Group 2 rats received 1 ml of DMSO instead of MNNG and were then treated in the same way as group 1. Analysis of pyloric mucosa sections for pepsinogen altered pyloric glands (PAPG) detected immunohistochemically after the animals were killed at week 16 revealed increased lesion numbers in group 1, with all gastric carcinogens and promoters examined. However, none of the five non-gastric carcinogens exerted any significant modification of PAPG development. The results strongly suggest that the experimental protocol consisting of the following four components: (i) adoption of PAPG as the end-point marker lesion; (ii) single dose of MNNG as initiator; (iii) test chemical administration for 14 weeks; and (iv) administration of saturated sodium chloride solution during the test chemical exposure, could be used effectively for the detection of gastric carcinogens as well as promoters of gastric carcinogenesis in a relatively short time period. PMID- 2225330 TI - Initiating activity of 3-tert-butyl-4-hydroxyanisole (3-BHA) and its metabolites in two-stage transformation of BALB/3T3 cells. AB - 3-tert-Butyl-4-hydroxyanisole (3-BHA) and its metabolites, tert-butyl-1,4 benzoquinone (BQ) and 3-tert-butyl-5-methoxy-1,2-benzoquinone (BHAoQ), were tested for initiating activity in a two-stage transformation assay using BALB/3T3 cells. Cells were treated first with a test chemical and then with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). In the absence of TPA the test chemicals did not induce cell transformation. With the promoting treatment, 3-BHA and BQ induced dose-dependent cell transformation. There were statistically significant increases in the proportion of dishes with transformed foci in the cultures treated with 30 micrograms/ml 3-BHA plus TPA (15 of 24 dishes, P less than 0.005) and with 0.4 microgram/ml BQ plus TPA (12 of 22 dishes, P less than 0.02) as compared to the cultures treated with DMSO plus TPA (5 of 24 dishes). BHAoQ caused a non-significant increase in transformation frequency in the presence of TPA. In conclusion, 3-BHA and BQ had an initiating activity in the cell transformation system and the potency of BQ was approximately 100 times higher than that of 3-BHA. PMID- 2225331 TI - Copper phthalocyanine labelled magnetic microcapsules: preparation, and binding properties in vitro and in vivo for mutagens having planar molecular structure. AB - Copper phthalocyanine tetrasulphonic acid (CPTS) functions were introduced into magnetic semi-permeable polyethyleneimine (PEI) microcapsules in order to create a recoverable scavenging system for trapping and biomonitoring, within the gastrointestinal cavity, of mutagens having a planar molecular structure. Stable ionic CPTS and covalent (thionylated CPTS, TCPTS) adducts to the microcapsule PEI were produced and shown to trap benzo[a]pyrene (B[a]P) in vitro in relation to the porphyrin/B[a]P ratio employed. 3-hydroxy B[a]P and B[a]P 3,6-dione from a crude B[a]P metabolite mixture, and a set of planar mutagens from crude opium/morphine pyrolysate mixtures could also be recovered in 7-86% yields after shaking with modified microcapsules followed by methanol/ammonia (50:1) desorption. Tetraols derived from B[a]P 7,8-diol-9,10 epoxide could also be recovered. Modified microcapsules were recovered magnetically from faeces of rats treated with [14C]B[a]P, and 45-51% of trapped radioactivity could be directly desorbed for HPLC assay compared with 30% for unmodified microscapsules. The relative extent of trapping by unmodified or CPTS- or TCPTS-modified microcapsules was different for various substrates, and it appears that the copper phthalocyanine tetrasulphonic acid moiety competes with another unidentified absorption/desorption structure in the microcapsules. These results show that selective and reversible trapping of carcinogens/mutagens having planar molecular structure can be achieved within the gastrointestinal tract. PMID- 2225332 TI - Complexes involving quercetin, DNA and Cu(II). AB - The genotoxic flavonoid, quercetin, was shown to bind to both double-stranded and single-stranded DNA with concomitant changes in absorption spectrum and fluorescence emission spectrum of quercetin. Quercetin and Cu(II) were shown to form a charge transfer complex that decayed in oxygen-dependent reaction(s) and this decay was accelerated by DNA. Analysis of the three component system, DNA- querectin--Cu(II), led to a discussion of the complexes likely to be involved in the initial reactions that lead, ultimately, to strand scission of DNA. PMID- 2225333 TI - Characterization and genotoxicity of DNA adducts caused by 2-naphthyl isocyanate. AB - Calf thymus DNA and M13mp9 RF DNA were modified with [ring-3H]2-naphthyl isocyanate (NIC) and analyzed by reverse-phase HPLC following enzymatic hydrolysis. In each case, essentially, a single radioactive component, which co chromatographed with authentic N4-2-naphthyl-carbamoyl-2'-deoxycytidine (NCdC), was detected. In order to explore the biological potential of this adduct, mp9 RF DNA modified with NIC was introduced into Escherichia coli strains using a calcium chloride technique. The plaque-forming efficiencies of DNA decreased with increasing adduct level, and the decreases were more pronounced in Uvr endonuclease-deficient strains (i.e. AB1886, uvrA; AB1885, uvrB; AB1884, uvrC) as compared to JM103 (Uvr endonuclease proficient) and JM101 RH03 (recA). These results suggest that these lesions, NCdC adducts, can be removed by the Uvr endonuclease repair system. Mutations were detected as the loss of ability of the bacteriophage to complement the defective beta-galactosidase of the host cells. Induction of SOS functions in the host cells enhanced the mutation frequency to 0.089%, i.e. greater than or equal to 4-fold greater than in non-SOS-induced cells, in transfections with RF DNA that contained 100 adducts/molecule. The mutagenic potency of this cytidine lesion is lower than that of the guanine-C8 adducts of 2-aminofluorene and 2-acetylaminofluorene as reported previously for this mutagenesis system. PMID- 2225334 TI - Specific inhibitory effect of dietary eicosapentaenoic acid on N-nitroso-N methylurea-induced mammary carcinogenesis in female Sprague-Dawley rats. AB - We have investigated the effects of two qualitatively different types of unsaturated fatty acids on N-nitroso-N-methylurea (NMU)-induced mammary carcinogenesis in female Sprague-Dawley rats. Semipurified diets containing 4.7% eicosapentaenoic acid (EPA) plus 0.3% linoleic acid or 5% linoleic acid were prepared. Animals maintained on these diets were given an i.v. injection of NMU (50 mg/kg body wt) at 50 days of age and killed 20 weeks later. Both tumor incidence and tumor number per rat were significantly lower in the EPA diet group (60.0% and 2.3 +/- 2.5 versus 93.3% and 5.1 +/- 4.5 respectively) for the 5% linoleic acid diet. Furthermore, the average weight of tumor material (total) per rat was significantly lower in the EPA as compared to linoleic acid diet group (2.9 +/- 4.2 g and 11.4 +/- 12.2 g respectively). Analysis of phospholipid fatty acids in the mammary tumors in the EPA diet group showed a higher proportion of C16:0, C18:2, omega-3 fatty acids C20:5 and C22:6 and a lower proportion of C20:4. Furthermore, mammary tumors in rats fed the EPA diet demonstrated significant reduction in prostaglandins. The results thus suggest that inhibition by EPA of NMU-induced mammary carcinogenesis may be mediated via the modulation of lipid metabolism and associated reduction in prostaglandin synthesis. PMID- 2225335 TI - Formation of 5-hydroxymethyl-2'-deoxyuridine in hepatic DNA of rats treated with gamma-irradiation, diethylnitrosamine, 2-acetylaminofluorene or the peroxisome proliferator ciprofibrate. AB - The peroxisome proliferator ciprofibrate was tested for its ability to induce DNA damage in the form of 5-hydroxymethyl-2'-deoxyuridine (HMdU), an adduct that results from the reaction of thymine in DNA with hydroxyl radicals. In order to quantify HMdU, DNA containing [3H]thymidine of high specific activity had to be obtained. Since hepatocytes normally have a very low rate of DNA synthesis, rats were subjected to partial hepatectomy to stimulate DNA synthesis and then were administered [methyl-3H]thymidine by three p.o., i.p. or i.v. injections 20, 22 and 24 h after partial hepatectomy; or by slow infusion through the portal vein, starting 20 h after partial hepatectomy for 4 h. The specific activity of DNA in rats receiving [3H]thymidine through the portal vein was considerably higher than in rats receiving p.o., i.p. or i.v. injections. Rats were then exposed to various doses of gamma-irradiation after partial hepatectomy and infusion of [6 3H]thymidine through the portal vein. DNA from the liver was extracted, enzymatically hydrolyzed and analyzed by HPLC. The percentage of HMdU in DNA increased in a dose-dependent manner. Rats were then treated with the carcinogens 2-acetylaminofluorene (AAF) or diethylnitrosamine (DEN) in conjunction with partial hepatectomy and infusion of [methyl-3H]thymidine. There was an increase in HMdU formation after a single administration of DEN or AAF. Another group of rats was fed a diet containing the peroxisome proliferator ciprofibrate for 3 weeks. After partial hepatectomy and infusion of [6-3H]thymidine, these rats were fed the same ciprofibrate-containing diet for 2-4 more weeks. HMdU was detected in DNA at 2-4 weeks after [6-3H]thymidine infusion, but the level at 4 weeks was nearly 50% less than at 2 weeks. This study shows that oxidative DNA damage in the form of HMdU is induced in the liver by gamma-irradiation, DEN, AAF and peroxisome proliferation. PMID- 2225336 TI - Analysis of the polycyclic aromatic hydrocarbon content of petrol and diesel engine lubricating oils and determination of DNA adducts in topically treated mice by 32P-postlabelling. AB - Engine lubricating oils are known to accumulate carcinogenic polycyclic aromatic hydrocarbons (PAHs) during engine running. Oils from nine petrol-powered and 11 diesel-powered vehicles, in addition to samples of unused oil, were analysed for PAH content and ability to form DNA adducts when applied topically to mouse skin. The levels of 19 PAHs, determined by GC, were in total, approximately 22 times higher in used oils from petrol engines than in oils from diesel engines. Male Parkes mice were treated with 50 microliters of oil daily for 4 days before they were killed and DNA isolated from skin and lung tissue. DNA samples were analysed by nuclease P1-enhanced 32P-postlabelling. Used oils from both diesel and petrol engines showed several adduct spots on PEI-cellulose plates at total adduct levels of up to 0.57 fmol/microgram DNA [approximately 60 times greater than in experiments with samples of unused oil in which adduct levels (0.01-0.02 fmol adducts/microgram DNA) were close to the limit of detection]. Higher adduct levels were generally formed by petrol engine oils than by diesel engine oils. Lung DNA contained similar total adduct levels to those in skin although the adduct maps were less complex. Total adduct levels correlated with extent of oil use in the engine, the total PAH concentration in oils and with the concentrations of certain individual PAHs present in the oils. An adduct spot that co-eluted with that of the major benzo[a]pyrene-DNA adduct accounted for 9 26% of the total adducts in skin DNA, and approximately 8% of the adducts in lung DNA, of mice treated with petrol engine oils. A major, and as yet unidentified, adduct spot comprised up to 30% of the total adducts in skin DNA, and up to 89% of the total adducts in lung DNA, of these animals. PMID- 2225337 TI - Distribution and metabolism of the natural anticarcinogen phenethyl isothiocyanate in A/J mice. AB - The distribution and metabolism of phenethyl isothiocyanate (PEITC), a naturally occurring anticarcinogen, was investigated in A/J mice. Mice were administered 5 mumol of [14C]PEITC (2 microCi/mouse) by gavage and killed at 1, 2, 4, 8, 24, 48 or 72 h after dosing. Radioactivity present in the spleen, heart, liver, lung, kidney, brain, urine and feces was measured. Lung, the target tissue of PEITC inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) lung tumorigenesis, showed maximum radioactivity between 4 and 8 h after dosing, suggesting this time period would be optimal for maximal inhibition by PEITC in A/J mice. Approximately 50% of the total radioactivity was excreted within 24 h after dosing with nearly 80% of radioactivity found in urine and feces at 72 h. Two metabolites were isolated by reverse-phase HPLC from urine of mice treated with PEITC. The identities of these metabolites were determined by comparison with synthetic standards and by NMR and MS. The major metabolite was a cyclic mercaptopyruvic acid conjugate, whereas the minor metabolite was an N acetylcysteine conjugate. Approximately 25% of the administered dose of PEITC was excreted as the cyclic mercaptopyruvic acid conjugate and 10% as the N acetylcysteine conjugate. These results suggest that urinary metabolites of PEITC may provide potentially useful dosimeters for this natural anticarcinogen. PMID- 2225338 TI - Metabolism of 2S-hydroxy-3-methylcholanthrene by rat liver microsomes. AB - Products formed in the metabolism of 2S-hydroxy-3-methylcholanthrene (2S-OH-3MC) by liver microsomes prepared from phenobarbital-treated rats were isolated by sequential use of reversed-phase and normal-phase HPLC. Metabolites of 2S-OH-3MC were characterized by UV-visible absorption, mass and circular dichroic spectra, and chiral stationary phase HPLC analyses. The metabolites that had been identified were 2S-hydroxy-3-hydroxymethylcholanthrene (2S-OH-3-OHMC), 3MC-2-one, 3MC-2-one 9,10-dihydrodiol, 8-hydroxy-2S-OH-3MC, a pair of stereoisomers 3MC (trans)-1R,2R-diol and (cis)-1S,2R-diol in a ratio of approximately 11:89, a pair of diastereomers 2S-OH-3MC 9R,10R-dihydrodiol and 2S-OH-3MC 9S,10S-dihydrodiol in a ratio of approximately 9:1, and a pair of diastereomers 2S-OH-3MC 11R,12R dihydrodiol and 2S-OH-3MC 11S,12S-dihydrodiol in a ratio of approximately 77:23. A few tentatively identified minor metabolites were 3-OHMC trans-1R,2R-diol, 10 hydroxy-2S-OH-3MC, a 9,10-dihydrodiol derived from 3MC cis-1S,2R-diol, and a 11,12-dihydrodiol and two diastereomeric 9,10-dihydrodiols derived from 2S-OH-3 OHMC. Since the racemic 2-OH-3MC is a known potent carcinogen and 2S-OH-3MC is the most abundant metabolite of 3MC, some of the 2S-OH-3MC metabolites identified in this study may be further converted to proximate and ultimate carcinogens which may contribute to the overall carcinogenicity exhibited by 3MC. PMID- 2225339 TI - Conjugated diene and trans fatty acids in a choline-devoid diet hepatocarcinogenic in the rat. AB - It has been postulated that the hepatocarcinogenicity of a choline-devoid diet in rats stems from peroxidation of liver lipids. We have investigated whether the diet contains conjugated dienes that could account directly for those detected in liver lipids of rats fed a choline-devoid diet. Analyses were performed on samples of corn oil and of a partially hydrogenated fat used to prepare semipurified choline-devoid and choline-supplemented diets, and on fat extracted from two pairs of diets, one set containing 5% corn oil and 10% partially hydrogenated fat, and the other only corn oil (15%). The analyses consisted of quantitation of conjugated dienes by UV spectrophotometry, separation of fatty acids with conjugated dienes by HPLC, and quantitation of trans fatty acids by IR spectrophotometry. Small levels of conjugated diene and trans fatty acids were present in the corn oil, but much higher amounts were found in the partially hydrogenated fat. HPLC analysis yielded distinct elution profiles for the fatty acids with conjugated dienes present in the two fats, and similar results were obtained with fat extracted from the diets. However, no differences were observed between choline-devoid and control choline-supplemented diets. The results indicate that caution must be exercised in interpreting data from UV analysis of tissue lipids of rats fed diets containing a partially hydrogenated fat. PMID- 2225340 TI - Conjugated diene and trans fatty acids in tissue lipids of rats fed an hepatocarcinogenic choline-devoid diet. AB - Groups of male Fischer-344 rats were fed two pairs of semi-purified choline devoid and choline-supplemented diets, one set containing 5% corn oil and 10% partially hydrogenated fat, and the other only corn oil (15%). Analyses were performed on lipids extracted from whole liver, liver nuclei and adipose tissue of the rats. The analyses consisted of quantitation of conjugated dienes by UV spectrophotometry, separation of fatty acids with conjugated dienes by HPLC and quantitation of trans fatty acids by IR spectrophotometry. Conjugated dienes and conjugated diene and trans fatty acids were observed in adipose tissue total lipids, at concentrations that reflected those in the diets fed. The same was true of trans fatty acids in liver lipids. However, no conjugated dienes, or fatty acids with conjugated dienes, were detected in liver lipids of rats fed the diets formulated with only corn oil. In contrast, conjugated dienes were detected in total and neutral lipids, but not in phospholipids, of whole liver and liver nuclei of rats fed the diets formulated with partially hydrogenated fat. The neutral lipids contained fatty acids with conjugated dienes that eluted with the retention time of conjugated diene fatty acids, present in the dietary partially hydrogenated fat. It is concluded that a choline-devoid diet, which is hepatocarcinogenic in the rat, does not induce a peroxidation of liver cell membrane lipids, and that not only trans fatty acids, but also fatty acids with conjugated dienes present in a partially hydrogenated fat, are absorbed and assimilated in rat tissue lipids. PMID- 2225342 TI - Distribution of phorbol ester TPA-induced structural chromosomal aberrations in HeLa cells. AB - In order to gain further insight into the mechanism of clastogenic action of the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), the localization and distribution of structural chromosomal aberrations on HeLa chromosomes was investigated. We have shown by the G-banding technique that TPA-induced chromosomal aberrations in HeLa cells have practically the same distribution as that occurring spontaneously in control cultures. About two-thirds of the breakpoints are located in areas of known fragile sites; about one-third is located in regions near known oncogenes. The tumor promoter TPA thus appears to enhance pre-existing mechanisms of an 'endogeneous' clastogenesis. PMID- 2225341 TI - Formation of cyclic deoxyguanosine adducts in Chinese hamster ovary cells by acrolein and crotonaldehyde. AB - Acrolein and crotonaldehyde are alpha,beta-unsaturated carbonyl compounds that form 1,N2-propanodeoxyguanosine adducts when reacted with DNA in vitro. These compounds are mutagenic in Salmonella, and crotonaldehyde is tumorigenic in rats. This study used immunoassay and 32P-postlabeling methods to determine if acrolein and crotonaldehyde form these adducts in cultured mammalian cells. Adduct levels were highest in Chinese hamster ovary cells exposed to acrolein (1 mM) with 162 mumol adduct/mol deoxyguanosine. Crotonaldehyde (10 mM) formed adduct at a level of 75 mumol/mol deoxyguanosine. 32P-Postlabeling analysis confirmed the presence of adducts in crotonaldehyde-treated cells. Persistence studies showed that adduct levels were unchanged if the cells were cultured for 6 h before DNA isolation. Mutagenicity studies were performed to determine the biological consequences of these adducts. Mutations were not observed due to the toxicity of the compounds. PMID- 2225343 TI - DNA sequencing of a mouse liver protein that binds selenium: implications for selenium's mechanism of action in cancer prevention. AB - Complementary DNA clones for liver protein 56K (SLP-56) were isolated by screening a lambda Zap mouse liver library. The cloned cDNAs represented the complete message. The correct reading frame was verified by alignment of the deduced amino acid sequence with that of peptides sequenced from the purified protein. The primary sequence has not been reported previously since homologous DNA sequences were not found in GenBank. Most importantly, the DNA sequence did not contain an in-frame TGA codon that would code for seleno-cysteine, as occurs in the prototypic selenoprotein, glutathione peroxidase. Hydropathy analysis suggested the protein was not a membrane-spanning protein. SLP-56 was previously localized as a cytosolic-soluble protein on the basis of cell fractionation experiments. The results suggest that SLP-56 is different from proteins whose synthesis and concentration are dependent upon selenium and require TGA to encode for selenocysteine. In this respect, SLP-56 appears to be similar to liver fatty acid binding protein (SLP-14) for which selenium is a ligand. Our working hypothesis is that selenium exerts its inhibitory effects on cell growth by modulating the properties of existing growth regulatory proteins. The two proteins that are readily labeled by selenium in many rodent tissues, SLP-56 and SLP-14, would fit into this category. PMID- 2225344 TI - Educational and occupational outcome in Prader-Willi syndrome. AB - An educational and occupational history was obtained for affected members of the Prader-Willi Syndrome Association (UK). Of 32 females and 29 males over 16 years of age (mean 23 years), over 45% attended mainstream infant schools, but by the time they reached junior and secondary schools the majority were in schools for children with learning disabilities. On reaching adulthood, 31% were attending adult training centres or day centres. Nearly one in six were in employment, usually of a sheltered type. The majority had no formal educational qualifications, but over 10% had at least one Certificate of Secondary Education and one person had three O levels. Nearly three-quarters of those with known intelligence quotients had IQs in the 70 to 100 range. The physical and behavioural characteristics of the study population closely resembled those reported in Prader-Willi syndrome by other authors, although it is possible that some members of the Prader-Willi Syndrome Association (UK) may not have Prader Willi syndrome. The findings highlight the heterogeneity in educational achievements associated with Prader-Willi syndrome, and illustrate the importance of assessing individual educational strengths and needs. PMID- 2225346 TI - Scene schemata and scripts in children's understanding of hospital. AB - In a first study, 90 children (aged 3-5 years) were shown a photograph of a hospital scene, and then asked to identify which of 12 separate items were present in the original scene. Children made more plausible than implausible errors, suggesting that they had well-organized schemata for hospital scenes. In a second study, we investigated children's knowledge of hospital-related routines and activities. A total of 152 children (aged 3-5, 6-8 and 9-10 years) were shown five photographs of hospital and five photographs of school, and asked to arrange each set to 'tell a story'. Children in different age groups showed relatively high agreement in their orderings, and also in selecting the 'most important photograph'. The data suggest that children's knowledge of hospital is organized around rudimentary schemata and scripts, which enable them to make very plausible inferences about hospital scenes and activities. PMID- 2225345 TI - Night waking in 1-year-old children in England. AB - A national sample of 1500 mothers of 1-year-old children received a postal questionnaire concerned with the sleeping patterns of their children. The response rate was 69%. Seventeen per cent of mothers reported that their 1-year old presented a moderate or severe sleep problem and 26% said their child woke at night on at least five nights a week. While these two measures correlated, 10% of those who reported their infant woke on at least five nights a week did not consider this to be a problem. Neither sex of infant, social class, method of infant feeding or numbers of house moves were associated with sleep problems. The pattern of results strongly suggest an association between night waking and other sleeping difficulties and stress for mothers. This was indicated by the association we found with complaints about housing, overcrowding, more negative attitudes toward motherhood, lower assessments of maternal well-being, lack of practical support from partners, the use of more negative adjectives to describe their baby and more frequent feelings of being dominated by their baby. While these associations may be explained by the stresses of living with a night-waking baby, it is also likely that a mother who is feeling somewhat depressed and negative toward her baby is more likely to see night waking as significant and as a problem. There were class differences in how parents coped with a shortage of space. Middle-class parents were more likely to put a baby in with a sibling while working class parents more often had the baby in their own room. Middle class parents were more likely to leave a night-waking baby to cry. PMID- 2225347 TI - Mutual support for families of children with eye cancer. AB - For parents to be told that their child has been diagnosed as having retinoblastoma is totally devastating. Retinoblastoma is a cancerous condition of the eye which occurs mostly in children, usually before the age of 3 years. To be confronted with the problem of sight loss and cancer is a tremendous shock. In appreciation of this, the staff of Moorfields Eye Hospital in London were well aware of the need and desire of parents to form a self-help group for mutual support during this traumatic period in parents' lives. The purpose of this article is to discuss the importance of forming a self-help group for families with children affected by retinoblastoma and to describe how the Retinoblastoma Society was established. PMID- 2225348 TI - Electrotonic influences on action potentials from isolated ventricular cells. AB - This work combines a theoretical study of electrical interactions between two excitable heart cells, using a variable coupling resistance, with experimental studies on isolated rabbit ventricular cells coupled with a variable coupling resistance to a passive resistance and capacitance circuit. The theoretical results show that the response of an isolated cell to an increased frequency of stimulation is strongly altered by the presence of a coupling resistance to another cell. As the coupling resistance gradually is decreased, the stimulated cell becomes able to respond successfully to more rapid stimulation, and then, at levels of coupling resistance that allow conduction between the two cells, the coupled pair of cells exhibits arrhythmic interactions not predicted by the intrinsic properties of either cell. The experimental results show that the isolated rabbit ventricular cell is extremely sensitive to even a very small electrical load, with shortening of the action potential by 50% with electrical coupling to a model cell (of similar input resistance and capacitance to the ventricular cell) as high as 1,000 M omega, even though the action potential amplitude and current threshold are very insensitive to the electrical load. PMID- 2225350 TI - Lymphatic pumping in response to changes in transmural pressure is modulated by erythrolysate/hemoglobin. AB - Red blood cells and lysate products (erythrolysate) are observed consistently in lymph draining acute and chronic inflammatory reactions and from tissues subjected to trauma or surgical procedures. Using hemoglobin as a marker for erythrolysate, we have measured hemoglobin in lymph up to the 10(-6) M range in a number of pathophysiological states. Data demonstrate that erythrolysate alters the pumping characteristics of lymphatic vessels. To test the effects of erythrolysate on lymphatic pumping, bovine lymphatics were suspended in an organ bath preparation with the vessels cannulated at both inflow and outflow ends. By raising the heights of the Krebs reservoir and the outflow catheters appropriately, a transmural pressure that stimulated pumping activity could be applied to the vessels. With a fixed transmural pressure of 6 cm H2O applied to the ducts, sheep erythrolysate depressed pumping activity between 40% and 100%, with dilutions containing between 10(-8) and 10(-5) M hemoglobin. Although the active principle in the red blood cells has not been characterized, evidence from precipitation purification experiments suggests that hemoglobin is an important component. Once suppressed, pumping could be restored in many but not all vessels (often to control levels) by elevating the distending pressure above 6 cm H2O. The relation between transmural pressure and fluid pumping is expressed as a bell shaped curve, with pumping increasing up to a peak pressure (usually 8 cm H2O) and declining at pressures above this level. By comparing pressure/flow curves, we were able to ascertain that hemoglobin shifted the lymphatic function curve to the right and, on average, reduced the maximum pumping capability of the vessels. We speculate that the presence of erythrolysate/hemoglobin in lymph may modulate the ability of lymphatic vessels to drain liquid and protein from the tissue spaces. PMID- 2225349 TI - Energy demand, supply, and utilization in hypoxia, and force recovery after reoxygenation in rabbit heart muscle. AB - In rabbit papillary muscle contracting at 20 degrees C in nitrogen at 0.2 Hz, glycolytic ATP formation is just enough to support the diminished contractile activity. Basal metabolism, important to maintain cellular function and integrity, is strongly inhibited. In the present study, we address the question of whether the inhibition of basal processes in hypoxia determines redevelopment of force in reoxygenation. By not stimulating the muscle during hypoxia, we try to make more ATP available for basal processes. Isometric force of papillary muscles (0.2-Hz stimulation) is measured before, during, and after 40 minutes of hypoxia. ATP formation and utilization in hypoxia are estimated from lactate production and changes in nucleotides and creatine compounds. After reoxygenation, muscles stimulated during hypoxia produce a steady-state force of 78% of the aerobic control; resting muscles recover to 94%. In contrast to expectation, lactate production in hypoxic resting muscles is only 30% of that in contracting ones. The findings indicate that basal metabolic rate of hypoxic muscles at rest is 14% of that of quiescent, well-oxygenated myocardium. We conclude that in hypoxic myocardium little ATP is available for basal metabolism, irrespective of the energy demand of the contractile system. It is therefore unlikely that the lower force found after reoxygenation in muscles stimulated during hypoxia is related to the degree of inhibition of basal processes. PMID- 2225351 TI - Nonuniform regional deformation of the pericardium during the cardiac cycle in dogs. AB - We hypothesized that local contact forces between the pericardium and the heart cause regional variation in pericardial deformation during the cardiac cycle, reflecting volume changes of the underlying cardiac chambers. To test this, we measured regional pericardial area over the right atrium (RA) and right ventricle (RV) with orthogonal pairs of sonomicrometers in six open-chest dogs. At a left ventricular end-diastolic pressure of 5 mm Hg, RV pericardial area paralleled RV volume, that is, shrinkage during ejection by 10 +/- 8% and expansion during filling. RA pericardial area was reciprocally related to RV pericardial area, with average expansion during ventricular ejection of 2 +/- 2%, thus paralleling RA volume during RV ejection. With volume loading, RV pericardial shrinkage during ejection increased to 14 +/- 6%, but the RA pericardial area change was no longer reciprocal (0 +/- 3% change during RV ejection). Elimination of contact forces by cardiac tamponade resulted in both marked attenuation of RV pericardial area changes and synchronization of the RV and RA pericardial area pattern; that is, both shrank during RV ejection. In two additional dogs, measurement of pericardial area over left ventricle and atrium showed similar results. We conclude that dynamic pericardial contact forces cause regional variation in pericardial deformation, which reflects volume changes of the underlying chambers. These findings imply that the influence of the pericardium on filling and ejection may be more complex than previously recognized, varying both by chamber and dynamically over the course of the cardiac cycle. PMID- 2225352 TI - Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes. AB - The patch-clamp technique was used to study the relation between pinacidil and intracellular ATP concentration [( ATP]i) on the activation of the outward K+ current in guinea pig ventricular myocytes. Pinacidil shortened the action potential duration, exhibiting stronger effect at 2 mM [ATP]i than at 5 mM [ATP]i. Pinacidil at 5 microM or higher concentrations activated the time independent outward current at potentials positive to -80 mV, and the pinacidil activated current was suppressed by increasing [ATP]i from 2 to 5 mM. The dose response curve of pinacidil at different [ATP]i showed a shift to the right and a depression of the maximum response at increased [ATP]i. The pinacidil-induced shortening of the action potential duration and outward current were inhibited by application of 0.3-1.0 microM glibenclamide. In single-channel current recordings, pinacidil activated the intracellular ATP-sensitive K+ channel current without changing the unitary amplitude, and increased open probability of the channel, an effect dependent on [ATP]i. The pinacidil-activated single channel current was blocked by glibenclamide. These results prove the notion that pinacidil activates the ATP-sensitive K+ channel current, which explains the action potential shortening in cardiac cells after application of pinacidil. PMID- 2225354 TI - Evidence for decreased coronary flow reserve in viable postischemic myocardium. AB - To try to unravel the complexity and heterogeneity of the "no-reflow" phenomenon and its underlying mechanisms, we studied tissue perfusion in reperfused heart muscle by using tracer microspheres in an anesthetized dog model of 90-minute coronary occlusion followed by reperfusion for 2 1/2 hours, 24 hours, or 1 week. Regional myocardial blood flow was determined both in basal flow conditions and during reactive hyperemia. The effect of intracoronary adenosine administration was examined, and the ultrastructure of postischemic myocardium was analyzed. In viable reperfused tissue (as delineated by triphenyltetrazolium chloride staining), reflow in basal conditions is unimpaired. Coronary flow reserve (as approximated by peak reactive hyperemic flow) is intact at the start of reperfusion, decreases by more than half after 2 1/2 hours, and recovers completely within 1 week. This impairment of coronary reserve can be relieved by intracoronary adenosine administration. On ultrastructural examination, the capillaries are patent. On the other hand, in irreversibly damaged myocardium, both the basal reflow impairment and the decrease in coronary flow reserve are severe and permanent. Coronary flow reserve is already decreased at the start of reperfusion, and the pharmacological intervention has no beneficial effect. Ultrastructurally, extracellular and intracellular edema invariably are present, whereas the vascular endothelium is damaged and the capillaries are packed with red blood cells. We conclude that the no-reflow phenomenon (i.e., mechanical obstruction to blood flow) is limited to infarcted tissue. In viable myocardium, however, coronary flow reserve is transiently diminished, probably because of washout and subsequent insufficient availability of the chemical mediator adenosine after breakdown and slow recovery of the precursor ATP pool. PMID- 2225353 TI - Neuropeptide Y modulates vasoconstriction in coronary microvessels in the beating canine heart. AB - The purpose of this study was to determine whether neuropeptide Y has a direct vasoconstrictor effect at low doses, mimicking the physiological plasma concentration on the specific site(s) of coronary arterial microvessels in in situ beating canine left ventricles. Coronary microvessels were directly observed by means of an intravital microscope and video system equipped with a floating objective. Epi-illuminated fluorescence coronary microangiography was performed in open-chest anesthetized dogs (n = 14) to examine the changes in internal diameter of epimyocardial arterial microvessels. Flow velocity of fluorescently labeled microshperes in capillaries was also measured (n = 6). To eliminate secondary effects of neuropeptide Y on coronary microvessels via autonomic nervous modulation, experiments were conducted under pharmacological blockade of the regional autonomic nervous system by intracoronary injection of propranolol, 50 micrograms/kg; phentolamine, 100 micrograms/kg; and atropine, 5 micrograms/kg. Aortic pressure and heart rate were kept constant during the experiments. Intracoronary infusion of three different doses of neuropeptide Y (1, 10, and 100 pmol/kg/min) for 5 minutes significantly constricted small microvessels (less than 100 microns in diameter) (-5.2 +/- 1.4%, -8.5 +/- 1.5%, and -14.0 +/- 1.7%; p less than 0.05 versus before neuropeptide Y at each dose), medium microvessels (100-200 microns in diameter) (-5.5 +/- 1.6%, -10.6 +/- 1.8%, and -16.8 +/- 2.1%, p less than 0.05 versus before neuropeptide Y at each dose), and large microvessels (greater than 200 microns in diameter) (-3.6 +/- 0.6%, -5.8 +/- 0.8%, and -10.0 +/- 1.1%; p less than 0.05 versus before neuropeptide Y at each dose) in a dose-dependent manner. Capillary flow velocity was reduced by 17.2 +/- 3.1% by an intracoronary dose of 100 pmol/kg/min of neuropeptide Y (p less than 0.05). The present study indicates that low doses of neuropeptide Y exert a homogeneous direct vasoconstrictor effect on various sizes of coronary arterial microvessels and reduce capillary flow velocity. These results suggest that neuropeptide Y may play a physiological role in modulating coronary microvascular tone. PMID- 2225355 TI - Reperfusion and readmission of oxygen. Pathophysiological relevance of oxygen derived free radicals to arrhythmogenesis. AB - We have examined the pathophysiological role of readmission of oxygen (and hence production of oxygen-derived free radicals) in the initiation of reperfusion induced arrhythmias by separating, on a temporal basis, readmission flow from readmission of oxygen. Isolated rat hearts (n = 12/group) were subjected to 10 minutes of regional ischemia and 10 minutes of reperfusion. In controls reperfused with oxygenated solution (Po2 greater than 600 mm Hg), 92% of hearts developed ventricular fibrillation (VF) during the first 20 seconds of reperfusion, whereas in hearts reperfused with hypoxic solution (Po2 9.3-12.2 mm Hg), the incidence of VF was only 17% (p less than 0.05). Subsequent readmission of control solution (Po2 greater than 600 mm Hg) to the latter group led, within 20 seconds, to the appearance of VF in seven of the 10 hearts (70%) that had not previously fibrillated. To examine whether hypoxic reperfusion had prevented VF or merely delayed its onset, the studies were repeated in separate groups of hearts with the duration of hypoxic reperfusion extended to 5 minutes. In addition, to examine the partial pressure dependence of the relation, the Po2 in the reperfusion solution was set at one of five different levels: greater than 600, 150-192.7, 69-85.6, 9.2-14.8, or 0.0 mm Hg. It was found that hypoxia merely delayed VF onset by 20-40 seconds and did not significantly reduce the incidence of VF, which was 83%, 92%, 67%, 58%, and 58%, respectively. This indicated that readmission of oxygen is unnecessary for the initiation of VF during reperfusion. The hearts that reverted to sinus rhythm during the ensuing 5 minutes (n = 8, 4, 5, 9, and 8, respectively) were used to assess the arrhythmogenic consequences of readmission of oxygen. When control solution (Po2 greater than 600 mm Hg) was readmitted, new episodes of VF were elicited within 20 seconds in a manner that was inversely proportional to the preceding Po2 (p less than 0.05), the incidence of new episodes of VF being 0%, 0%, 40%, 67%, and 86%, respectively. The arrhythmogenic effect of readmission of oxygen was not the result of a sudden increase in heart rate, because a similar arrhythmogenic effect of readmission of oxygen was seen in separate groups of hearts that were paced (350 beats/min) throughout hypoxia and readmission of oxygen. In conclusion, readmission of flow and readmission of oxygen are independent determinants of reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2225356 TI - Pulmonary model to predict the effects of series ventricular interaction. AB - To fully describe the mechanisms of diastolic interaction between the right ventricle and left ventricle, it is necessary to understand how a change in right ventricular output (Qrvo) is transmitted across the pulmonary circulation. This series ventricular interaction is manifest as the temporal response in left ventricular filling (Qlvf) to a change in Qrvo. To quantify series interaction we used a three-element, two-parameter model of the pulmonary circulation. The parameters represented the pulmonary arterial and venous resistance and pulmonary vascular compliance. Using beat-to-beat values of mean pressure and flow measured at the input and output of the pulmonary circulation during the transient response to caval or pulmonary artery occlusion, we estimated the parameters for this model in eight open-chest dogs under control conditions, after autonomic blockade, and after fully opening the pericardium. From 110 separate data episodes, the average values of the pulmonary arterial and venous resistance and pulmonary vascular compliance were 0.14 +/- 0.08 mm Hg.sec/ml and 4.81 +/- 3.17 ml/mm Hg (+/- SD). These estimates were insensitive to the simultaneous effects of autonomic reflexes and direct ventricular interaction, so they uniquely measure the bulk transport properties of the pulmonary circulation. The time constant, which measures the response of Qlvf to a change in Qrvo, averaged 0.26 +/- 0.15 second, which implies that effects of series interaction on Qlvf are manifest within one beat. The model was also able to predict the dynamic response of Qlvf to changes in Qrvo and thus can be used to measure and predict the effects of series interaction in the intact cardiopulmonary system. PMID- 2225357 TI - Time course of cellular enzyme release in dog heart injury. AB - The transport time of enzyme from heart to plasma was studied in two experimental models. First, the enzyme alanine aminotransferase was slowly infused into the left ventricular wall in open-chest dogs. The half-life for the washout of alanine aminotransferase activity into plasma was 20 +/- 4 minutes (mean +/- SEM, n = 8) and was not different in ischemic and normally perfused tissue. From measurements of arteriovenous differences in alanine aminotransferase activity and left ventricular blood flow, it was concluded that 77 +/- 14% of total enzyme washout from ischemic tissue occurred by direct entry into the bloodstream. The corresponding value for the vascular permeability-surface area product was 264 +/ 55 ml.kg-1.hr-1. For a second model, we studied myocardial enzyme release into plasma after abrupt heart injury induced by 10 minutes of calcium-free coronary perfusion followed by reintroduction of calcium (calcium-paradox mechanism). The half-life for the release into plasma was 1.9 +/- 0.2 hours (mean +/- SEM, n = 6) and was again not influenced by sustained ischemia. Slower washout, as observed for this second model, is consistent with increased interstitial protein space and corresponds to a permeability--surface area product between 135 and 285 ml.kg 1.hr-1. These results were used to calculate the time course of cellular enzyme leakage from the rate of enzyme release into plasma in various forms of heart injury. Significant shifts between the time curves of evolving cellular injury and enzyme release into plasma are observed after 2 hours of ischemia followed by coronary reperfusion, but not after permanent ischemia. PMID- 2225358 TI - Stimulation of serotonin2 receptors in the ventrolateral medulla of the cat results in nonuniform increases in sympathetic outflow. AB - Topical application of the serotonin2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane or DOI, in a dose of 30 micrograms/side to the intermediate area of the ventrolateral surface of the medulla produced a significant increase in mean arterial pressure with no significant change in heart rate both in intact animals (n = 8) and in cervically vagotomized animals (n = 3). The pressor response of DOI was blocked by pretreatment of the intermediate area with ketanserin, a serotonin2 antagonist (n = 7). Pretreatment with intravenous phentolamine did not block the pressor response of DOI (n = 3). However, this pressor response could be counteracted by intravenous propranolol (n = 5) or by bilateral stellate ganglionectomy (n = 3). These data suggest that sympathoexcitation by centrally applied DOI selectively increased cardiac inotropy but not chronotropy. Further studies indicate that DOI increased contractile force without increasing heart rate and that the positive inotropic effect of DOI could be counteracted by bilateral stellate ganglionectomy. Bilateral microinjections of DOI into the subretrofacial nucleus in a dose of 100 ng (n = 3) and a dose of 300 ng (n = 3) increased mean arterial blood pressure by 23 +/- 2 and 44 +/- 6 mm Hg, respectively, without producing any changes in heart rate. These data suggest that DOI has a central site of action in the ventrolateral medulla, presumably at the subretrofacial nucleus, which leads to selective sympathoexcitation of the cardiac ventricles. PMID- 2225359 TI - Studies of recombinant plasminogen activator inhibitor-1 in rabbits. Pharmacokinetics and evidence for reactivation of latent plasminogen activator inhibitor-1 in vivo. AB - The pharmacokinetics of human recombinant plasminogen activator inhibitor-1 (rPAI 1) was studied in rabbits. Latent rPAI-1 (0-2 units of tissue-type plasminogen activator neutralizing activity per microgram protein); reactivated rPAI-1 (approximately 150 units/micrograms); and chloramine T-oxidized, nonreactivatable rPAI-1 (approximately 0.7 units/microgram) were studied. The pharmacokinetic parameters for the disposition of rPAI-1 antigen after an intravenous bolus injection of 1.0 or 2.5 mg/kg rPAI-1 were very similar for all three forms: the initial volume of distribution was approximately 60 ml/kg, the initial half-life in plasma was 6 minutes, and the plasma clearance was approximately 4 ml/kg/min. The disposition of PAI activity after injection of reactivated rPAI-1 was similar to that of rPAI-1 antigen. Injection of latent rPAI-1 was associated with a nearly threefold increase in the specific activity of circulating PAI-1 from 2 units/micrograms to 5.0 +/- 1.1 units/micrograms (p less than 0.01) within 1 minute, followed by a cumulative 25-fold increase in specific activity over 1 hour (p = 0.01). In contrast, the specific activity of oxidized or reactivated preparations of rPAI-1 did not increase in the first several minutes after injection. These findings support the existence of a fast-acting but low-capacity mechanism for the reactivation of rPAI-1 in vivo. PMID- 2225360 TI - Differences in transient outward currents of feline endocardial and epicardial myocytes. AB - Whole-cell voltage-clamp experiments were performed on enzymatically dissociated single ventricular myocytes harvested from feline endocardial and epicardial surfaces. The studies were designed to test the hypothesis that the differences in the amplitude of transient outward current (Ito) contribute to the difference in action potential configuration between endocardial and epicardial myocytes. In the control state, action potentials recorded from epicardial cells demonstrated a prominent notch between phases 1 and 2, and membrane current recordings displayed a prominent Ito, whereas in endocardial cells the notch in action potentials and Ito were small. External application of 4-aminopyridine (2 mM) reduced the amplitudes of notch and Ito in epicardial cells but not in endocardial cells. After application of 4-aminopyridine (2 mM) and caffeine (5 mM), the notch and Ito were abolished completely in both endocardial and epicardial cells. The first component of Ito (Ito1) was present in all epicardial cells studied (n = 20); it was absent in 12 of the 20 endocardial cells, and a small Ito1 was present in the remaining eight endocardial cells. The mean amplitude of Ito1 was significantly greater in epicardial than in endocardial cells. At a test voltage of +80 mV, the amplitude of Ito1 was 102.0 +/- 47.7 pA/pF in epicardial cells and 3.3 +/- 3.3 pA/pF in endocardial cells (p less than 0.01). The second component of Ito (Ito2) was present in all endocardial (n = 30) and epicardial (n = 30) cells studied. The amplitude of Ito2 was significantly greater in epicardial than in endocardial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225361 TI - Beta-adrenergic regulation of the muscarinic-gated K+ channel via cyclic AMP dependent protein kinase in atrial cells. AB - Cholinergic and beta-adrenergic stimulations of ionic currents are major physiological mechanisms in the regulation of heart rate and contractility. Muscarinic receptor stimulation is known to reduce beta-adrenergic effects on calcium current via reduction of cyclic AMP. Whether the beta-adrenergic stimulation affects the muscarinic response is not known. I report here that the beta-adrenergic agonist isoproterenol enhanced the muscarinic-activated K+ channel activity in rat atrial cells. Application of cyclic AMP-dependent protein kinase or its catalytic subunit to the cytoplasmic side of the membrane augmented the acetylcholine-activated K+ channel activity twofold to threefold. Increases in channel activity produced by isoproterenol or cyclic AMP-dependent protein kinase were associated with fourfold to fivefold and approximately twofold increases in the mean open and closed time durations, respectively. Alkaline phosphatase treatment reversed these effects. These results suggest that cyclic AMP-dependent phosphorylation of the K+ channel or associated regulatory proteins modulates the gating kinetics of the channel. This mechanism may be important in the regulation of pacemaker activity and, thus, the heart rate during beta adrenergic stimulation. PMID- 2225362 TI - Comments on "Effect of cellular uncoupling by heptanol on conduction in infarcted myocardium". PMID- 2225363 TI - Clinical spectrum of ventricular tachycardia. PMID- 2225364 TI - Effects of adenosine on human coronary arterial circulation. AB - Adenosine is a potent vasodilator used extensively to study the coronary circulation of animals. Its use in humans, however, has been hampered by lack of knowledge about its effects on the human coronary circulation and by concern about its safety. We investigated in humans the effects of adenosine, administered by intracoronary bolus (2-16 micrograms), intracoronary infusion (10 240 micrograms/min), or intravenous infusion (35-140 micrograms/kg/min) on coronary and systemic hemodynamics and the electrocardiogram. Coronary blood flow velocity (CBFV) was measured with a 3F coronary Doppler catheter. The maximal CBFV was determined with intracoronary papaverine (4.5 +/- 0.2.resting CBFV). In normal left coronary arteries (n = 20), 16-micrograms boluses of adenosine caused coronary hyperemia similar to that caused by papaverine (4.6 +/- 0.7.resting CBFV). In the right coronary artery (n = 5), 12-micrograms boluses caused maximal hyperemia (4.4 +/- 1.0.resting CBFV). Intracoronary boluses caused a small, brief decrease in arterial pressure (similar to that caused by papaverine) and no changes in heart rate or in the electrocardiogram. The duration of hyperemia was much shorter after adenosine than after papaverine administration. Intracoronary infusions of 80 micrograms/min or more into the left coronary artery (n = 6) also caused maximal hyperemia (4.4 +/- 0.1.resting CBFV), and doses up to 240 micrograms/min caused a minimal decrease in arterial pressure (-6 +/- 2 mm Hg) and no significant change in heart rate or in electrocardiographic variables. Intravenous infusions in normal patients (n = 25) at 140 micrograms/kg/min caused coronary vasodilation similar to that caused by papaverine in 84% of patients (4.4 +/- 0.9.resting CBFV). At submaximal infusion rates, however, CBFV often fluctuated widely. During the 140-micrograms/kg/min infusion, arterial pressure decreased 6 +/- 7 mm Hg, and heart rate increased 24 +/- 14 beats/min. One patient developed 1 cycle of 2:1 atrioventricular block, but otherwise, the electrocardiogram did not change. In eight patients with microvascular vasodilator dysfunction (delta CBFV, less than 3.5 peak/resting velocity after a maximally vasodilating dose of intracoronary papaverine), the dose-response characteristics to intracoronary boluses and intravenous infusions of adenosine were similar to those found in normal patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2225365 TI - Sex differences in control of cutaneous blood flow. AB - Women are far more likely than men to suffer from Raynaud's disease. The purpose of this study was to determine whether there are gender differences in local or central control of cutaneous blood flow that could account for the increased incidence of Raynaud's disease in women. To assess cutaneous blood flow, hand blood flow (HBF), finger blood flow (FBF), or skin perfusion (SP) was measured by fluid plethysmography, mercury strain-gauge plethysmography, or laser Doppler spectroscopy, respectively, in 47 volunteers. Basal HBF in men exceeded that of women (12.1 +/- 2.0 versus 6.2 +/- 1.5 ml/100 ml/min). Likewise, FBF in men surpassed that of women (19.5 +/- 4.1 versus 7.7 +/- 1.8 ml/100 ml/min). Similarly, SP in men was greater than that of women (270 +/- 42 versus 81 +/- 16 perfusion units). However, after total body warming (to induce a thermal sympatholysis), HBF in women exceeded that of men, suggesting that the lower basal HBF in women was due to increased sympathetic outflow to the extremities. Mental stress and deep inspiration reduced HBF and SP in men. Paradoxically, both of these maneuvers increased HBF and SP in women. To determine whether these paradoxical responses in women were due to the women's elevated basal sympathetic tone, these experiments were repeated after total body cooling in men to increase sympathetic tone and after total body warming in women to reduce sympathetic tone. Total body cooling reduced HBF and SP in men. Under these conditions, mental stress and deep inspiration induced vasodilation. In women, total body warming for 10 minutes increased HBF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225366 TI - Mortality after 10 1/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial. AB - The Multiple Risk Factor Intervention Trial (MRFIT) is a randomized primary prevention trial that tested the effect of a multifactor intervention program on coronary heart disease (CHD) mortality in 12,866 high-risk men aged 35-57 years. Men were randomly assigned to either a special intervention (SI) program, which consisted of dietary advice for lowering blood cholesterol levels, counseling aimed at cessation for cigarette smokers, and stepped-care treatment for hypertension for those with elevated blood pressure, or to their usual sources of health care within the community (UC). Among the 12,866 randomized men, 8,012 (62%) were hypertensive at baseline. For this subgroup, mortality rates with 10.5 years of follow-up were lower for the SI than for the UC group by 15% (p = 0.19) for CHD and 11% (p = 0.13) for all causes. These results reflected more favorable outcomes for SI compared with UC hypertensive men during the 3.8 posttrial years (March 1982 through December 1985) than during the preceding 6-8 years (through February 1982). During the posttrial years, death rates were lower for SI than for UC men by 26% (p = 0.09) for CHD and 23% (p = 0.02) for all causes. For those with diastolic blood pressure equal to or more than 100 mm Hg, this posttrial trend was a continuation of a trend during the trial; therefore, with 10.5 years of follow-up, death rates were markedly lower for SI than for UC by 36% (p = 0.07) for CHD and 50% (p = 0.0001) for all causes. Similarly, for those without baseline resting electrocardiographic abnormalities, the favorable posttrial outcome for the SI group was a continuation of a trend during the trial. In contrast, for those with baseline diastolic blood pressure of 90-99 mm Hg and for those with baseline resting electrocardiographic abnormalities, the favorable posttrial mortality findings for the SI group were a reversal of unfavorable trends recorded during the trial. Two factors appear to have contributed to this more favorable mortality trend for the SI group: 1) a change in the diuretic treatment protocol for SI men about 5 years after randomization, which involved replacement of hydrochlorothiazide with chlorthalidone at a daily maximum dose of 50 mg; and 2) a favorable effect of intervention on nonfatal cardiovascular events during the trial years. In addition, delay until the full impact of beneficial effects on mortality end points from smoking cessation and cholesterol lowering could have contributed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2225367 TI - Ten-year follow-up of survival and myocardial infarction in the randomized Coronary Artery Surgery Study. AB - The Coronary Artery Surgery Study (CASS) randomized 780 patients to an initial strategy of coronary surgery or medical therapy. Of medically randomized patients, 6% had surgery within 6 months and a total of 40% had surgery by 10 years. At 10 years, there was no difference in cumulative survival (medical, 79% vs. surgical, 82%; NS) and no difference in percentage free of death and nonfatal myocardial infarction (medical, 69% vs. surgical, 66%; NS). Patients with an ejection fraction of less than 0.50 exhibited a better survival with initial surgery treatment (medical, 61% vs. surgical, 79%; p = 0.01). Conversely, patients with an ejection fraction greater than or equal to 0.50 exhibited a higher proportion free of death and myocardial infarction with initial medical therapy (medical, 75% vs. surgical, 68%; p = 0.04) although long-term survival remained unaffected (medical, 84% vs. surgical, 83%; p = 0.75). There were no significant differences either in survival and freedom from nonfatal myocardial infarction, whether stratified on presence of heart failure, age, hypertension, or number of vessels diseased. Thus, 10-year follow-up results confirm earlier reports from CASS that patients with left ventricular dysfunction exhibit long term benefit from an initial strategy of surgical treatment. Patients with mild stable angina and normal left ventricular function randomized to initial medical treatment (with an option for later surgery if symptoms progress) have survival equivalent to those patients randomized to initial surgery. PMID- 2225369 TI - Blood pressure level, trend, and variability in Dunedin children. An 8-year study of a single birth cohort. AB - In a birth cohort of children in the Dunedin Multidisciplinary Health and Development Study in New Zealand, resting blood pressures were recorded biennially five times from age 7 to 15 years. Using previously described methods, we examined the level, trend, and variability of blood pressures in those children with at least three readings. The level, trend, and variability of height, weight, and body mass index were compared among six separate groups of children. Two groups were categorized on the basis of high systolic pressure levels, one with low variability and the other with high variability, which was thought to resemble adult labile hypertension. Two additional groups were categorized on the basis of increasing and decreasing blood pressure trends; the fifth group had consistently low blood pressures, and the sixth group consisted of the remaining children. There were significant differences among the groups for the level of all the physical measurements and for the trend of body mass index. No significant differences were found among the groups for gender or socioeconomic status. A parental history of high blood pressure, stroke, or heart attack was significantly more common in the first two groups. PMID- 2225368 TI - Change of left atrial systolic pressure waveform in relation to left ventricular end-diastolic pressure. AB - The relation between the left atrial systolic pressure waveform and left ventricular end-diastolic pressure was observed in 17 patients who underwent diagnostic cardiac catheterization. Left atrial pressure and left ventricular pressure were simultaneously recorded from a multisensor catheter before and during angiotensin infusion. Left ventricular systolic pressure and left ventricular end-diastolic pressure were 133 +/- 17 and 12.3 +/- 3.2 mm Hg, respectively, before angiotensin infusion and increased to 168 +/- 18 (p less than 0.01) and 19.4 +/- 4.5 mm Hg (p less than 0.01), respectively, during infusion. The left atrial systolic pressure curve consisted of two positive waves -a first wave (A) and a second wave (A'). The A and A' wave pressures were 11.6 +/- 2.3 and 10.2 +/- 3.9 mm Hg, respectively, before angiotensin infusion and 16.5 +/- 2.9 (p less than 0.01) and 18.1 +/- 4.7 mm Hg (p less than 0.01), respectively, during infusion. The ratio of A'/A of left atrial systolic pressure was 0.81 +/- 0.27 before angiotensin infusion and 1.08 +/- 0.14 (p less than 0.01) during infusion. The ratio of A' to A of left atrial systolic pressure was linearly related to left ventricular end-diastolic pressure before and during (p less than 0.01) angiotensin infusion. The amplitude of the A wave exceeded that of the A' wave at normal left ventricular end-diastolic pressures. However, as the left ventricular end-diastolic pressure increased either at rest or during angiotensin infusion, the amplitude of the A' wave increased and often exceeded that of the A wave. These results suggest that the second (A') wave might be attributed to the increased reflection associated with increased left ventricular end-diastolic pressure. PMID- 2225371 TI - Late potentials and inducible ventricular tachycardia in surgically repaired congenital heart disease. AB - We compared signal-averaged electrocardiography with invasive electrophysiological study in patients after surgical repair of congenital heart disease to determine if potentially useful correlations exist between the two methods for assessment of risk for ventricular tachycardia. Thirty-one patients (age, 1-49 years; mean, 10.6 years) with congenital heart disease repaired with right ventriculotomy or postrepair right bundle branch block (77% postoperative tetralogy of Fallot) who had electrophysiological study were studied with signal averaged electrocardiography. Patients were classified by electrophysiological study results as having no inducible ventricular tachycardia, nonsustained ventricular tachycardia, or sustained ventricular tachycardia. Signal-averaged electrocardiograms were examined for the duration of low-amplitude (less than or equal to 40 microV) QRS signal, duration of total QRS, and root-mean-square voltage of the terminal 40 msec of the QRS. Low-amplitude terminal root-mean square voltage of 100 microV or less had 91% sensitivity and 70% specificity for ventricular tachycardia inducible by electrophysiological study. Similar sensitivity but less specificity were seen using the criterion of 20 msec or more total low-amplitude QRS signal (initial plus terminal) or using total QRS duration of 128 msec or more. There was a weaker association between terminal low amplitude QRS signal of 15 msec or more and inducible ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225370 TI - Baffle fenestration with subsequent transcatheter closure. Modification of the Fontan operation for patients at increased risk. AB - Ventricular dysfunction, elevated pulmonary vascular resistance, and residual distal pulmonary artery distortion contribute to early mortality after a Fontan operation; they may be transient or reversible. A baffle fenestration, allowing right-to-left shunting, maintains cardiac output and limits right atrial pressure. A baffle fenestration was surgically created at the time of a modified Fontan repair in 20 consecutive patients. Risk factors included pulmonary artery pressure of 18 mm Hg or more, end-diastolic pressure of 12 mm Hg or more, valvar regurgitation, pulmonary artery distortion, pulmonary vascular resistance of 2 Woods' units or more, ventricular outflow obstruction, and complex anatomy. Nineteen of 20 patients survived. After the operation, mean arterial oxygen saturation was 86%, mean right atrial pressure was 15 mm Hg, and mean duration of pleural effusions was 6 days. Twelve of 19 survivors tolerated early test occlusion and had permanent transcatheter umbrella closure. Four patients failed early test occlusion, with a significant decrease in venous O2 saturation and a rise in central venous pressure, due to ventricular dysfunction, pulmonary artery distortion, or aortopulmonary collaterals. Three of four had successful late closure of the fenestration after correction of these abnormalities. PMID- 2225373 TI - Prognostic value of electrophysiology testing in asymptomatic patients with Wolff Parkinson-White pattern. AB - The prognostic value of electrophysiology testing was studied in 75 asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern. All patients underwent electrophysiology testing at entry to the study and were followed up annually for a total of 348 patient-years (median, 4.3 years). There were 44 male and 31 female patients, and age at enrollment ranged from 7 to 77 years (mean, 34 +/- 14 years). The median effective refractory period of the accessory pathway was 293 msec (interquartile range, 280-310 msec), and the median shortest RR interval between preexcited beats during atrial fibrillation (SRR) [corrected] was 274 msec (240-320 msec). Twenty-three patients had an SRR of 250 msec or less and eight patients had a median shortest SRR interval of 200 msec or less. Twelve patients had inducible sustained reciprocating tachycardia, 10 patients had inducible nonsustained reciprocating tachycardia, and 23 patients had inducible sustained atrial fibrillation. Twenty patients (27%) lacked retrograde conduction over the accessory pathway. No patient died suddenly during a median follow-up of 4.3 years. Six patients (8%) became symptomatic with documented supraventricular tachycardia, of whom two underwent operative ablation of their accessory pathways. No patient with absent retrograde accessory pathway conduction during the electrophysiology study became symptomatic. Inducible sustained or nonsustained reciprocating tachycardia at electrophysiology study did not predict the development of subsequent symptomatic supraventricular tachycardia. Nine patients lost preexcitation during follow-up. Age at enrollment (relative risk/decade, 1.4; 95% confidence interval, 1.0-1.8) and anterograde accessory pathway refractory period (relative risk, 1.06/10 msec; 95% confidence interval, 1.0-1.12) were independent predictors of loss of preexcitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225372 TI - Prognostic value of radionuclide angiography in medically treated patients with coronary artery disease. A comparison with clinical and catheterization variables. AB - To evaluate the usefulness of multiple measures from rest and exercise radionuclide angiography (RNA) in predicting cardiovascular death and cardiovascular events (death or nonfatal myocardial infarction) and to assess the prognostic usefulness of the RNA relative to clinical and catheterization data, we studied 571 stable patients with symptomatic coronary artery disease who had upright rest/exercise first-pass RNA within 3 months of catheterization and were medically treated. With a median follow-up of 5.4 years, 90 patients have died from cardiovascular causes, and 147 patients have either died or suffered a nonfatal myocardial infarction. Using the Cox regression model and a preselected group of RNA variables, the most important RNA predictor of mortality was exercise ejection fraction (chi 2 = 81, p less than 0.00001). Neither rest ejection fraction nor the change in ejection fraction from rest to exercise contributed additional predictive information. Two other RNA study variables, the change in heart rate from rest to exercise and rest end-diastolic volume index, did contribute additional prognostic information to the exercise ejection fraction (chi 2 = 23, p less than 0.0001). Compared with noninvasive clinical data (history, physical examination, electrocardiogram, and chest radiograph), RNA variables were considerably more predictive of mortality (chi 2 = 71 [clinical variables] versus chi 2 = 104 [RNA]). Remarkably, the strength of the relation of RNA variables with mortality was equivalent to that of the set of catheterization variables previously demonstrated in our large angiographic population to be prognostically important (chi 2 = 104 [RNA] versus chi 2 = 102 [catheterization variables]). The RNA contained 84% of the information provided by clinical and catheterization descriptors combined. Furthermore, the RNA contributed significant additional prognostic information to the clinical and catheterization data (chi 2 = 13.6, p = 0.0035). For cardiovascular events, the relative prognostic usefulness of the RNA was similar, although relations with this outcome were generally weaker. Descriptors from the rest/exercise RNA exhibit a powerful relation with long-term outcomes and can be useful in defining risk, even when clinical and catheterization data are available. PMID- 2225374 TI - Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. AB - There is a varying hormonal activation in heart failure. To be able to evaluate this activation and relate it to prognosis, we took blood samples at baseline and after 6 weeks from 239 patients with severe heart failure (all in New York Heart Association class IV) randomized to additional treatment with enalapril or placebo. In this study (CONSENSUS), which has previously been reported, there was a significant reduction in mortality among patients treated with enalapril. The present data show in the placebo group a significant positive relation between mortality and levels of angiotensin II (p less than 0.05), aldosterone (p = 0.003), noradrenaline (p less than 0.001), adrenaline (p = 0.001), and atrial natriuretic factor (p = 0.003). A similar relation was not observed among the patients treated with enalapril. Significant reductions in mortality in the groups of patients treated with enalapril were consistently found among patients with baseline hormone levels above median values. There were significant reductions in hormone levels from baseline to 6 weeks in the group of patients treated with enalapril for all hormones except adrenaline. There were no correlations between these changes in hormone levels. Summarily, there is a pronounced but variable neurohormonal activation in heart failure even in patients with similar clinical findings. This activation is reduced by enalapril therapy. The results suggest that the effect of enalapril on mortality is related to hormonal activation in general and the renin-angiotensin system in particular. PMID- 2225375 TI - Excretion of thromboxane A2 and prostacyclin metabolites before and after exercise testing in patients with and without signs of ischemic heart disease. AB - We addressed the hypothesis that platelets are not activated in association with effort-induced myocardial ischemia in stable coronary disease. Seventy-two patients undergoing a diagnostic bicycle exercise test were stratified according to the development of chest pain (yes/no, 33/39) and of exercise-induced ST segment depression of at least 200 microV in the electrocardiogram (yes/no, 12/60). Noninvasive indexes of platelet activation and of platelet/vessel wall interaction (urinary excretion of the 2,3-dinor-metabolites of thromboxane A2 [Tx M] and prostacyclin [PGI-M], respectively) were analyzed in samples collected in the basal state and after the test. Basal Tx-M and PGI-M did not differ in patients with (236 +/- 35 and 131 +/- 22 pg/mg creatinine, respectively) and without (185 +/- 16 and 101 +/- 13 pg/mg creatinine, respectively) chest pain, or in those with (178 +/- 45 and 162 +/- 41 pg/mg, respectively) and without (216 +/ 22 and 104 +/- 11 pg/mg, respectively) ST-segment depression during the test. Patients without chest pain or without ST-segment depression moderately increased (p less than 0.05) their urinary Tx-M (by 21% and 13%, respectively) and PGI-M (by 28% and 23%, respectively) after exercise. No significant increases were observed in those developing chest pain or ST depression during exercise. These data indicate that effort-induced myocardial ischemia is not associated with an increase in platelet activation or platelet/vessel wall interaction in patients with stable coronary disease. PMID- 2225376 TI - Effect of long-term exercise on regional myocardial function and coronary collateral development after gradual coronary artery occlusion in pigs. AB - The effect of myocardial ischemia, induced by long-term exercise, on regional myocardial function and coronary collateral development was examined in pigs after gradual occlusion of the left circumflex coronary artery (LCx) with an ameroid occluder. Thirty days after surgery, regional myocardial function and blood flow were assessed during exercise in 22 pigs separated into exercise (n = 12) and sedentary groups (n = 10). The exercise group trained on a treadmill for 25 +/- 1 days, 30-50 min/day, at heart rates of 210-220 beats/min. After 5 weeks, another exercise test was performed. In the exercise group, after training, we observed an improvement in systolic wall thickening, expressed as a percentage of rest, in the collateral-dependent LCx region from 64 +/- 8% to 87 +/- 6% (p less than 0.01) at moderate exercise levels (220 beats/min) and from 45 +/- 7% to 73 +/- 7% (p less than 0.01) at severe exercise levels (265 beats/min). Transmural myocardial blood flow in the LCx region expressed as a ratio of flow in the nonoccluded region of the left ventricle also increased significantly (p less than 0.01) during severe exercise after 5 weeks. The sedentary group showed an improvement in systolic wall thickening in the LCx region during moderate exercise compared with the initial exercise test (p less than 0.05) but no significant change in systolic wall thickening or myocardial blood flow ratios during severe exercise after 5 weeks. We conclude that long-term exercise after gradual LCx coronary artery occlusion in pigs improves myocardial function and coronary collateral reserve in collateral-dependent myocardium during exercise. PMID- 2225377 TI - Are the kinetics of technetium-99m methoxyisobutyl isonitrile affected by cell metabolism and viability? AB - To investigate the role of cell viability and metabolism on the myocardial kinetics of a new tracer, technetium-99m-methoxyisobutyl isonitrile (Tc-99m MIBI), 250 microCi/l Tc-99m-MIBI was infused in isolated rat hearts under constant flow conditions. The hearts were studied after inducing irreversible damage by cytochrome c oxidase inhibitor sodium cyanide (n = 8) or sarcolemmal membrane detergent Triton X-100 (n = 8). The control hearts (n = 6) received no toxins. Mean Tc-99m-MIBI peak accumulation activity was significantly reduced after cyanide (51.1 +/- 44.2% of control, p less than 0.01) and Triton (13.8 +/- 2.7% of control, p less than 0.001) administration. Kinetic studies also showed marked reduction in accumulation rates and marked increase in clearance rates for cyanide (p less than 0.01) and Triton (p less than 0.01) groups compared with controls. Potential changes in regional flow distribution were assessed using microspheres. When peak accumulation activity was corrected for these changes, there remained significant differences between the groups. In the cyanide and Triton groups, irreversible cell injury was confirmed by creatine kinase and lactate dehydrogenase release, triphenyl tetrazolium chloride staining, and electron microscopy. All the cells were viable in the control group. We conclude that the accumulation and clearance kinetics of Tc-99m-MIBI are significantly affected by cell viability. Tc-99m-MIBI kinetics appear to be dependent on sarcolemmal integrity and to a lesser extent on aerobic metabolism. PMID- 2225378 TI - Effect of tachycardia on regional function and transmural myocardial perfusion during graded coronary pressure reduction in conscious dogs. AB - The purpose of the present study was to examine subendocardial flow and function during graded coronary pressure reduction to determine the effect of tachycardia on the lower autoregulatory pressure limit (critical coronary pressure) in unanesthetized dogs. During atrial pacing at a rate of 200 beats/min, subendocardial flow measured by radioactive microspheres averaged 1.55 +/- 0.34 ml/min/g and remained unchanged as pressure was reduced over the autoregulatory plateau from 84 +/- 10 to 59 +/- 7 mm Hg. Further reductions in coronary pressure to below a critical coronary pressure of approximately 60 mm Hg were associated with concomitant reductions in subendocardial flow and the endocardial-epicardial flow ratio during tachycardia. Although regional function remained constant over the autoregulatory plateau, there was a rightward shift of the coronary pressure function relation during ischemia in response to a steady-state increase in rate from 100 to 200 beats/min. Reductions in regional wall thickening began when coronary pressures reached 38 +/- 7 mm Hg at a heart rate of 100 beats/min and 61 +/- 6 mm Hg at a heart rate of 200 beats/min (p less than 0.005). Similar critical coronary pressure values were obtained for subendocardial segment shortening. Relations between subendocardial flow and myocardial function measured by both transmural wall thickening and subendocardial segment shortening were linear during pacing at a heart rate of 200 beats/min with relative reductions in wall thickening related to reductions in subendocardial flow on a nearly one-to-one basis. The results of this study demonstrate that there is a shift in the lower limit of subendocardial autoregulation during tachycardia as manifest by the onset of subendocardial ischemia at a higher distal coronary artery pressure. The shift in critical coronary pressure relates to an increase in resting flow requirements due to increased demand and diminished subendocardial vasodilator reserve at any given coronary pressure secondary to a reduction in the time available for diastolic subendocardial perfusion during tachycardia. PMID- 2225379 TI - Uptake and retention of hexakis (2-methoxyisobutyl isonitrile) technetium(I) in cultured chick myocardial cells. Mitochondrial and plasma membrane potential dependence. AB - The fundamental myocellular uptake and retention mechanisms of hexakis (2 methoxyisobutyl isonitrile) technetium(I) (Tc-MIBI), a technetium-99m-based myocardial perfusion imaging agent, are unresolved. Because of the lipophilic cationic nature of Tc-MIBI, it may be distributed across biological membranes in response to transmembrane potential. To test this hypothesis, net uptake and retention of Tc-MIBI in cultured chick embryo ventricular myocytes were determined under conditions known to alter mitochondrial and plasma membrane potentials. Isovolumic depolarization of plasma membrane potentials in 130 mM extracellular K (Ko) 20 mM extracellular Cl buffer reduced net accumulation of Tc MIBI from 171 +/- 16 (control) to 29 +/- 3.3 fmol intracellular Tc-MIBI/mg protein.nM extracellular Tc-MIBI. Unidirectional influx of Tc-MIBI in cells depolarized in 30 mM Ko buffer was also reduced; a resting plasma membrane potential of -87 +/- 6 mV was calculated from the Goldman flux equation using normal Ko/high Ko Tc-MIBI influx ratios. Addition of the potassium ionophore valinomycin to cells incubated in 130 mM Ko buffer to additionally depolarize mitochondrial membrane potentials further reduced net uptake of Tc-MIBI to levels comparable to that found in nonviable freeze-thawed preparations ([Tc-MIBI]i/[Tc MIBI]o = 1). By depolarizing mitochondrial (and in part plasma membrane) potentials with the protonophores 2,4-dinitrophenol and carbonyl cyanide m chlorophenylhydrazone (CCCP) Tc-MIBI was rapidly depleted from 181 +/- 16 (control) to 16 +/- 2.6 and 31 +/- 4.2 fmol/mg protein.nMo, respectively, with kinetics that did not correlate with loss of cellular ATP content. CCCP alone inhibited 90 +/- 3% of net accumulation or 66 +/- 3% of unidirectional influx of Tc-MIBI in a concentration-dependent manner. By hyperpolarizing mitochondrial membrane potentials with the K+/H+ ionophore nigericin or the ATP synthase inhibitor oligomycin, net uptake and retention of Tc-MIBI were increased by 60 +/ 9% and 375 +/- 20%, respectively. Caffeine, as well as the respiratory chain electron transport inhibitor rotenone, did not significantly alter net cell uptake (p greater than 0.2). These data indicate that the fundamental myocellular uptake mechanism of Tc-MIBI involves passive distribution across plasma and mitochondrial membranes and that at equilibrium Tc-MIBI is sequestered within mitochondria by the large negative transmembrane potentials. PMID- 2225380 TI - Optimizing the exercise test for pharmacological investigations. AB - Exercise trials in cardiology are often hindered by inconsistent approaches to exercise testing. These inconsistencies include the choice of exercise protocol, exercise end points, points of analysis, and absence or misuse of gas exchange data. Gas exchange techniques greatly enhance the accuracy with which cardiopulmonary function is assessed by exercise. Commonly used protocols are not always appropriate for all patients or all studies. Both cardiovascular disease and the exercise protocol can have an important impact on the relation between changes in work rate and oxygen uptake. Ramp protocols appear to offer the greatest promise for assessing cardiopulmonary function. Analyzing hemodynamic and gas exchange responses at several points submaximally, in addition to those at peak exercise, can add important information concerning the efficacy of a drug. A great deal of confusion continues to hinder the application of the gas exchange anaerobic threshold, and many of the commonly used testing end points are not reliable. PMID- 2225381 TI - Left ventricular ejection fraction may not be useful as an end point of thrombolytic therapy comparative trials. AB - In the era of comparative and adjunctive trials in reperfusion therapy, the need to develop alternative end points for mortality reduction is clear. Left ventricular ejection fraction, which has been commonly used as a surrogate, is problematic due to missing values, technically inadequate studies, and lack of correlation with mortality results in controlled reperfusion trials performed to date. In this paper, we present a composite clinical end point that includes, in order, severity of adverse outcome death, hemorrhagic stroke, nonhemorrhagic stroke, poor ejection fraction (less than 30%), reinfarction, heart failure, and pulmonary edema. Such a composite index may be useful to detect true therapeutic benefit in reperfusion trials without necessitating greater than 20-30,000 patient enrollment. PMID- 2225382 TI - Adenosine. Renewed interest in an old drug. PMID- 2225383 TI - Extension of clinical trials. 10 1/2 year follow-up of the Multiple Risk Factor Intervention Trial. PMID- 2225384 TI - Coronary artery surgery study revisited. Limitation of the intent-to-treat principle. PMID- 2225385 TI - Level, trend, and variability of blood pressure in childhood and adolescence. PMID- 2225386 TI - The partial Fontan procedure. A new concept and its clinical application. PMID- 2225387 TI - Arterial complications of interventional cardiac catheterization in patients with congenital heart disease. PMID- 2225388 TI - Clinical electrophysiological studies and the Wolff-Parkinson-White pattern. PMID- 2225389 TI - Autoregulation and heart rate. PMID- 2225390 TI - Coarctation of the aorta in infants. PMID- 2225391 TI - Reversible segmental cardiac dysfunction. PMID- 2225392 TI - Clinical competence in exercise testing. A statement for physicians from the ACP/ACC/AHA Task Force on Clinical Privileges in Cardiology. PMID- 2225393 TI - Cardiovascular surgery 1989. Council on Cardiovascular Surgery, American Heart Association scientific sessions. New Orleans, Louisiana, November 13-16, 1989. Proceedings. PMID- 2225394 TI - Splenic septic emboli in endocarditis. AB - The significance of septic emboli to the spleen is inferred by the frequency of septic emboli in general seen in patients with left-sided infective endocarditis who are referred for valve replacement. To determine the proper management of splenic infarcts and abscess due to septic emboli, we retrospectively reviewed the records of 108 patients with left-sided endocarditis who underwent valvular surgery at the University of Illinois Hospital from 1980 through 1988. Intravenous drug abuse was the etiology in 68% (n = 73). The incidence of splenic infarcts and abscess was 19% (n = 20), but an incidental finding of splenic infarcts was found in 38% (n = 11) of 29 asymptomatic patients who had computed tomograms. Streptococci and staphylococci were the causative organisms in 85% (n = 17). Localized findings were absent in 90% of splenic infarcts and abscesses. Abdominal computed tomograms were diagnostic of the sequelae of splenic septic emboli in 100%. No patient had intra-abdominal bleeding complications associated with cardiopulmonary bypass. Splenectomy was performed in 50% (n = 10) of patients 3-24 days (mean, 11.2 days) after valve replacement. Indications for splenectomy included persistent sepsis in 60% (n = 6), large (greater than 2 cm) and peripheral lesions in 30% (n = 3), and splenic rupture in 10% (n = 1). Perioperative mortality of patients who underwent splenectomy was 30% (n = 3). The following conclusions can be drawn: 1) Splenic septic embolus is common in endocarditis. 2) Abdominal computed tomography should be performed for all patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225395 TI - Clinical and Doppler echocardiographic evaluation of bioprosthetic valve failure after 10 years. AB - Four hundred thirteen consecutive patients underwent valve replacement with a bioprosthesis between 1976 and 1982. Aortic valve replacement was performed in 240 patients, mitral valve replacement in 132 patients, and multiple valve replacement in 41. The Carpentier-Edwards porcine (n = 336), Angell-Shiley porcine (n = 23), Hancock porcine (n = 11), and the Ionescu-Shiley pericardial valves (n = 43) were inserted. Follow-up between 5 and 12 years postoperatively was 98% complete. Freedom from structural valve deterioration was 72 +/- 7%, 59 +/- 9%, and 59 +/- 9%, respectively, after aortic, mitral, and double valve replacement. The risk of structural valve deterioration and reoperation for valve related complications was significantly increased with the Ionescu-Shiley pericardial prosthesis. The risk for reoperation was inversely related to patient age. Postoperative Doppler echocardiographic studies in 87% of available patients revealed a subgroup of asymptomatic patients with evidence of structural valve deterioration. These patients (n = 61) had significantly reduced prosthetic valve areas (aortic less than 1 cm2, mitral less than 1.7 cm2), elevated resting transvalvular gradients (aortic greater than 40 mm Hg), or moderate-to-severe regurgitation. In summary, postoperative Doppler echocardiographic examination identified asymptomatic patients with structural valve dysfunction. These patients must be followed up carefully to determine the optimal timing of reoperation. PMID- 2225396 TI - Differences in Hancock and Carpentier-Edwards porcine xenograft aortic valve hemodynamics. Effect of valve size. AB - We prospectively compared the hemodynamic performance of Hancock and Carpentier Edwards bioprosthetic aortic valves in a randomized study of 100 patients. A total of 47 patients received the Hancock valve, and 53 received the Carpentier Edwards valve. Mean pressure gradients were measured using micromanometer catheters and cardiac outputs by thermodilution. Multiple measurements were made in each patient with atrial pacing, volume infusion, and inotropic drugs for a total of 319 observations. The pressure gradients and Gorlin valve areas showed significant scatter caused by both flow-dependent and patient-dependent variability. Mean transvalvular pressure gradients were therefore compared after adjustment for flow rate and for random interpatient differences using analysis of variance and covariance. Pressure gradients were lower and Gorlin valve areas larger for the Hancock valve than for the Carpentier-Edwards valve, but the differences were significant only for the smaller valve sizes. Compared with the Carpentier-Edwards valve, the mean pressure gradients were significantly lower for the Hancock 19-mm modified orifice (MO) valves (16.9 versus 31.7 mm Hg, p = 0.04), for the 21-mm valves (15.2 versus 22.4 mm Hg, p = 0.003), and for the 23 mm MO valve (9.2 versus 13.8 mm Hg, p = 0.04). The Gorlin areas were also significantly larger for the Hancock 19-mm MO valve (0.85 versus 0.77 cm2, p = 0.004) and the 21-mm MO valve (1.11 versus 0.89 cm2, p = 0.0009) but not for the 23-mm MO valve (1.59 versus 1.14, p = 0.08). Mean gradients and valve areas were not different for any of the larger valve sizes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225397 TI - Chordal replacement in mitral valve repair. AB - Chordal replacement greatly extends the possibility of repair of atrioventricular valves. Both glutaraldehyde-tanned xenograft pericardial chordae (GTXP) and extruded polytetrafluorethylene chordae (ePTFE) heal to papillary muscles and cusps. Neither type elongates or shrinks. GTXP may thicken and stiffen with time. ePTFE is covered by a normal fibrosa and intima (a new chorda is grown around the ePTFE suture) experimentally and in small sizes (e.g., CV 5), retains flexibility. The results of late follow-up (5-10 years) with GTXP chordae and early follow-up (6-58 months) with ePTFE chordae are encouraging. PMID- 2225398 TI - Coronary artery pattern and outcome of arterial switch operation for transposition of the great arteries. AB - A successful outcome of an arterial switch operation (ASO) for dextro transposition of the great arteries (D-TGA) depends in large part on the transfer of the coronary arteries to the neoaorta without distortion or narrowing. However, the origins and distribution of the coronary arteries are quite variable in D-TGA; therefore, the entire experience with ASO at the Children's Hospital in Boston was reviewed. From 1983 through November 1989, 314 patients underwent surgery for D-TGA with the intent to perform an ASO. An ASO was actually performed in 290 patients, and 20 patients died, with 12 deaths (4.2%) clearly related to problems with the coronary arteries (CA deaths). The ASO was aborted to a Senning operation in 24 patients (7.6%), primarily due to coronary anatomy. Eight coronary patterns were identified and related to the outcome of the ASO. In 182 patients with the "usual" coronary pattern for D-TGA (i.e., anterior descending and circumflex arteries from the left sinus and right coronary artery from the right sinus), five CA deaths occurred, and two patients had Senning operations. Sixty-seven patients had right coronary and circumflex arteries from the right sinus and anterior descending arteries from the left sinus. Three CA deaths occurred, and one patient had a Senning operation. Single right coronary artery was found in 14; 12 had ASOs with three CA deaths (25%); and two had Senning operations. One late death was due to diffuse narrowing of the single right coronary artery. Single left coronary artery occurred in 11 patients, and seven had ASO with no early but one late "sudden" death, whereas four had Senning operations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225399 TI - Midterm surgical results of arterial switch operation for transposition of the great arteries with intact septum. AB - Between April 4, 1984, and December 31, 1987, 156 consecutive neonates with simple transposition of the great arteries underwent an arterial switch operation (ASO) at our institution. Surgery was performed before the age of 15 days in 96%, and patient weight was less than 3 kg in 28%. Seventeen patients (10.9%) died after surgery. One patient was lost to follow-up. Of the 138 survivors, two died of myocardial infarction 35 and 40 days, respectively, after surgery. They were the only late deaths, and actuarial survival rates were 87% (70% confidence level [CL], 83-89%) at 45 days and 87% (70% CL, 68-95%) at 52 months. Another patient had a myocardial infarction 50 days after surgery and is well 50 months later. Pulmonary stenosis was observed in 14 patients (10.3%) during the first year after surgery; two patients were reoperated on 10 and 12 months, respectively, after ASO. Aortic regurgitation was observed in 17 patients: two had grades II and III, respectively, aortic regurgitation on aortography; in 15 patients, it was detected only by Doppler examination. At the last follow-up (2-52 months after ASO; mean, 27.3 +/- 11.3 months), all patients were asymptomatic and taking no medication. On bidimensional echocardiography, left ventricular fractional shortening was normal at rest in all survivors but one. One patient had junctional rhythm, and one had Wenckebach periods; the remainder were in sinus rhythm. For as long as 5 years after ASO, late death and reintervention were rare; 99% of the survivors were asymptomatic and had sinus rhythm and good systemic ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225400 TI - Right ventricular growth after transventricular pulmonary valvotomy and central aortopulmonary shunt for pulmonary atresia and intact ventricular septum. AB - We performed transventricular pulmonary valvotomy as initial surgery in 22 consecutive patients with pulmonary atresia and intact ventricular septum who had a patent infundibulum. Nineteen patients also had placement of a central aortopulmonary shunt. All patients survived surgery, and 16 patients have had preoperative and later postoperative catheterizations. The purpose of this study was to determine the response of the right ventricle to transventricular pulmonary valvotomy with regard to relief of right ventricular hypertension and growth of the entire right ventricle, including tricuspid valve, right ventricular volume, and right ventricular outflow tract. Right ventricular systolic pressure decreased from 111.3 +/- 31.7 mm Hg before initial surgery to 65.6 +/- 26.2 mm Hg. Right ventricular end-diastolic volume increased from 59.1 +/- 39.3% of predicted normal before initial surgery to 114.6 +/- 63.2% at late follow-up catheterization. Tricuspid valve anulus circumference also increased in size from 73.2 +/- 21.3% of predicted normal before initial surgery to 90.4 +/- 22.8% at late follow-up catheterization. Only one patient (6%) required a transanular right ventricular outflow tract patch at the time of biventricular repair. Twenty of 22 patients (91%) either have had or are awaiting biventricular repair. We conclude that transventricular pulmonary valvotomy and central aortopulmonary shunt can be performed safely in newborn infants with pulmonary atresia and intact ventricular septum who have a patent infundibulum. Effective valvotomy relieves right ventricular hypertension, allows for excellent right ventricular and tricuspid valve growth, and optimizes potential for biventricular repair. PMID- 2225402 TI - Early diagnosis and surgical intervention of acute aortic dissection by transesophageal color flow mapping. AB - To determine whether transesophageal color Doppler echocardiography (TEE) is useful for the early diagnosis and surgical intervention in acute aortic dissection, 57 serial patients with acute aortic dissection were examined. These patients were evaluated by TEE with either the single-plane probe (39 patients) or the biplanar probe (18 patients) just after admission. The intimal flap was detected in all patients, and there were 18 patients with type A dissection and 39 patients with type B dissection. The entry was visualized in 83% of type A dissection cases and in 90% of type B dissection cases. In two of 18 patients examined with the biplanar probe technique, the entry was detected in the longitudinal view only. Emergency operations were performed in 18 patients with type A dissection and in 10 patients with ruptured type B dissection. Twenty-nine of 39 patients with type B dissection were treated conservatively. The operative mortality rate of patients with type A dissection was 22%, and that of patients with ruptured type B dissection was 60%. The major advantage of TEE is its ease of application at the bedside or in the operating room, which allows immediate and accurate diagnosis of acute aortic dissection for emergency surgical intervention. Biplanar TEE provides additional acoustic windows, ease of spatial orientation, and more accurate visualization of entry. TEE is a useful and powerful diagnostic tool for acute aortic dissection, and by using this method, one may achieve a more rapid and aggressive surgical approach for patients with acute aortic dissection. PMID- 2225401 TI - Atrial cardiomyoplasty after Fontan-type procedures. AB - The purpose of right atrial cardiomyoplasty is to increase atrial-pulmonary flow in patients undergoing Fontan-type procedures. We developed two surgical techniques to bypass the right ventricle, followed by right atrial cardiomyoplasty with a stimulated latissimus dorsi muscle flap (LDMF). In 10 goats, the left LDMF was transferred into the chest by removal of the second rib. After sternotomy, the right atrial appendages of five goats (group 1) were connected to the distal main pulmonary artery with polytetrafluoroethylene tubing and the proximal pulmonary trunks were ligated. In the other five goats (group 2), under cardiopulmonary bypass, bioprosthetic valves were implanted into the inferior venae cavae. The tricuspid orifice was closed, and the atriopulmonary connection was performed. The left LDMF was sutured over the right atrium and stimulated using synchronous 30-Hz bursts of impulses delivered by a Medtronic Cardiomyostimulator. Hemodynamic studies were performed in the acute phase. Right atrial, pulmonary arterial, and aortic pressures were assessed. Cardiac output was measured using ultrasonic flow studies. LDMF stimulation restored pulsatile pressure patterns in the pulmonary artery and increased the cardiac output. These observations were more evident in the model with caval valvular implant. This functional "ventricularization" of the right atrium could improve long-term results after Fontan-type procedures and extend operative indications. Chronic experimental studies are necessary to evaluate the diastolic and systolic functions of the neo-right ventricle. PMID- 2225403 TI - Perioperative arrhythmias after Fontan repair. AB - Arrhythmias are well-recognized sequelae of the Fontan repair. A prospective analysis of perioperative arrhythmias after Fontan repair was performed. Thirty three patients had 24-hour ambulatory monitoring on the day before surgery and for 24 hours immediately after surgery; the 27 surviving patients had an additional 24-hour study on the seventh postoperative day. The most common preoperative rhythm was normal sinus, which was present in 79%. Hemodynamically significant preoperative arrhythmias were present in only two patients-atrial flutter (n = 1) and complete heart block (n = 1). Other asymptomatic preoperative arrhythmias included ectopic atrial rhythm (n = 2), supraventricular tachycardia (n = 1), accelerated junctional rhythm (n = 1), and frequent ventricular premature beats (n = 1). On the first postoperative day, the most common rhythm was accelerated junctional rhythm, which was present in 48%. Hemodynamically significant arrhythmias were present in nine patients (27%) -rapid accelerated junctional rhythm (rate, greater than 190 beats/min) (n = 3), complete heart block (n = 2), atrial flutter (n = 2), supraventricular tachycardia (n = 1), and ventricular tachycardia (n = 1). Three of six deaths occurring between postoperative days 2 and 7 were in patients with rapid accelerated junctional rhythm and associated low cardiac output. On the seventh postoperative day, the most common rhythm was normal sinus, which was present in 41%. Nine of the 27 surviving patients had complete resolution of their arrhythmias between postoperative days 2 and 7. On postoperative day 7, hemodynamically significant arrhythmias were present in four patients-atrial flutter (n = 2) and complete heart block (n = 2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225404 TI - Partial anomalous pulmonary venous return. AB - Anomalous pulmonary venous return from the left lung is an extremely rare condition that is reported sporadically and in general in case reports. From 1964 through 1988, we identified 13 patients with this condition, all of whom underwent surgical correction. This represents the single largest reported institutional experience with this anomaly. The patients ranged in age from 15 months to 40 years. Seven were asymptomatic, and six had symptoms ranging from recurrent pulmonary infection to moderate congestive heart failure. Six had anomalous venous return from the entire left lung, and seven had anomalous return from the upper lobe only. Eight of the patients had associated cardiovascular anomalies. Four of the patients underwent surgical correction via a sternotomy approach with cardiopulmonary bypass to allow correction of coexisting intracardiac anomalies. The remaining patients underwent surgical repair through a left thoracotomy. The technique included high ligation and division of a persistent left superior vena cava with anastomosis to the left atrium at the site of partial excision of the atrial appendage. There were no deaths and only one complication in our series. PMID- 2225405 TI - Hypoplastic left heart syndrome. Outcome after initial reconstruction and before modified Fontan procedure. AB - The outcome and clinical course before modified Fontan procedure were reviewed for 200 patients with hypoplastic left heart syndrome who underwent initial reconstructive surgery between August 1985 and March 1989. The median age at the time of initial reconstruction was 6 days (range, 1 day to 7.2 months). In 28 patients, a right modified Blalock-Taussig shunt was used; in 172 patients, a central shunt was placed. Additional procedures (n = 41) performed in 38 patients (median age, 5 months; range, 6 days to 17.5 months) were revision of systemic-to pulmonary shunt (n = 15), arch reconstruction (n = 8), balloon angioplasty of arch obstruction (n = 7), atrial septectomy (n = 4), pulmonary artery angioplasty (n = 2), tricuspid valve annuloplasty or replacement (n = 4), and modified Glenn shunt (n = 1). There was no significant difference in the frequency of additional procedures performed more than 30 postoperative days in the survivors compared with the nonsurvivors. Actuarial survival rates were 0.66 (1 month), 0.48 (12 months), and 0.44 (18 months). Seventy percent of all deaths occurred during the initial admission, with 32% resulting from acute cardiovascular collapse during the first postoperative day. There was no statistical difference in actuarial survival when assessed by the type of shunt used or by anatomical subtype or when the influence of additional interventions was considered. Substantial improvement in outcome may be possible if immediate perioperative mortality can be reduced. We speculate that some of the intermediate mortality (30 days to 1 year) may be related to the effects of chronic exposure of the right ventricle to volume overload at systemic pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225406 TI - Resource use and cost of initial coronary revascularization. Coronary angioplasty versus coronary bypass surgery. AB - Although there is intense interest in the cost-saving potential of therapeutic alternatives, most studies have analyzed hospital charges rather than actual economic costs. To analyze cost differences rigorously, we studied 115 patients undergoing initial elective angioplasty (percutaneous transluminal coronary angioplasty, PTCA) and 274 patients undergoing initial elective surgery (coronary artery bypass graft surgery, CABG). Detailed resource consumption profiles were constructed and used to estimate the cost savings from switching a patient from CABG to PTCA. Four cost-accounting methods were used in the analysis; each method made different assumptions about the costs that would vary and the costs that would be fixed according to the number of procedures performed. The variable costs in the four methods were the 1) cost of supplies, 2) cost of personnel and supplies, 3) average direct costs, and 4) average direct costs plus allocated hospital overhead. The mean hospital charges for CABG patients were $19,644 versus $9,556 for PTCA patients (p less than 0.0001). The estimated cost difference between CABG and PTCA was substantially less than the $10,088 difference in charges, however, with net savings of 19%, 46%, 53%, and 78% of charges using cost-accounting methods 1-4, respectively. Thus, although the initial hospital charges for PTCA are significantly less than for CABG, the actual economic cost savings may be significantly overestimated by the use of hospital charge data. PMID- 2225407 TI - Clinical evaluation of single versus multiple mammary artery bypass. AB - The superior patency and clinical advantages of internal mammary artery (IMA) grafting are well established. However, the relative benefits of routine multiple IMA grafting remain uncertain. To determine whether routine multiple compared with single IMA utilization improved survival of patients undergoing coronary bypass procedures, 1,063 patients were prospectively allocated, beginning in 1984, to divergent management strategies of single (group 1, n = 420) versus multiple IMA grafting (group 2, n = 643). Subsequent analysis of anatomical extent of disease and preoperative baseline risk factors showed no differences (p = NS) between the two groups. All variables reflecting operative technique were similar (p = NS) for the two groups, except 74% of group 1 patients with multivessel disease received a single IMA graft, whereas 71% of group 2 patients with multivessel disease received multiple IMAs (p less than 0.05). By multivariate analysis, impairment of left ventricular ejection fraction, acute evolving myocardial infarction, advanced age, and unstable angina were incremental risk factors for mortality (all p less than 0.03), but group assignment (p = 0.4) and ultimate therapy were not (p = 0.6). Survival probabilities (expressed as 30-day group 1/group 2; 4-year group 1/group 2) were overall (0.97/0.98; 0.93/0.90), elective (0.98/0.99; 0.97/0.92), acute (0.95/0.97; 0.89/0.88), age of less than 65 years (0.98/0.99; 0.97/0.93), age of 65 years or older (0.93/0.97; 0.84/0.89), ejection fraction of 0.40 or more (0.97/0.99; 0.95/0.94), ejection fraction of less than 0.40 (0.95/0.96; 0.87/0.82), nondiabetic (0.98/0.98; 0.94/0.91), and diabetic (0.92/0.97; 0.88/0.87). No differences in survival were significant (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225408 TI - Use of single internal mammary artery grafts in older patients. AB - The indications for use of the internal mammary artery as a coronary bypass conduit in older patients are not clearly established. Between January 1985 and December 1988, 786 patients received single internal mammary artery grafts alone (717) or in conjunction with other procedures (69). Of these patients, 341 were 65 years of age or older (mean, 69.3 years). This group was compared with those patients less than 65 years of age (mean, 56.2 years). There were no significant differences between the two groups in the incidence of diabetes mellitus; the number of distal coronary anastomoses; left ventricular wall motion score; the frequency of isolated bypass procedures, reoperations, or emergent operations; or the durations of aortic clamping and cardiopulmonary bypass. The older group contained more women (34.9% versus 20.7%) and more patients with left main coronary artery disease (15.5% versus 9.4%) (p less than 0.01). No significant differences in the frequency of reoperation for hemorrhage, perioperative infarction, neurological deficits, requirements for intra-aortic balloon pumping, sternal wound infections, necessity for prolonged ventilatory support, or 30-day mortality (2.7% versus 3.2%) were observed. The length of postoperative hospitalization was greater in the older group (11.8 versus 10.2 days) (p = 0.02). Blinded histological examination of biopsies from 61 internal mammary artery grafts (34 patients less than 65 years, 27 patients greater than or equal to 65 years) showed no significant differences in luminal area or wall thickness. No significant degenerative changes were observed in either group. We conclude that the use of the internal mammary artery for bypass grafting in older patients is safe and may provide long-term benefit. PMID- 2225409 TI - Early and late results after isolated coronary artery bypass surgery in 159 patients aged 80 years and older. AB - We have studied 159 patients 80 years of age or older who have had isolated coronary artery bypass grafting (CABG) since 1977. Eighty-seven percent have had surgery since 1984. Two thirds of the patients were male, and the mean age was 82 years. Most patients (97%) were in New York Heart Association (NYHA) functional class III or IV, 89% had unstable/postinfarction angina pectoris, and 67% had rest pain. Almost half (47%) required preoperative admission to the coronary care unit, 6% required preoperative use of an intra-aortic balloon pump, and 20% were operated on emergently. Significant left main coronary artery disease (greater than or equal to 50% stenosis) was present in 41%. Ten patients (6.3%) died within 30 days of surgery, with seven more patients dying during the same hospital admission or soon after transfer to another institution. This resulted in an overall hospital mortality of 10.7%. The median hospital stay was 10 days. On univariate analysis, the significant predictors of hospital mortality were NYHA IV, angina at rest, preoperative admission to the coronary care unit, emergency operation, ejection fraction less than 0.50, and the presence of mitral regurgitation. On multivariate analysis, ejection fraction less than 0.50 was the only significant risk factor (p less than 0.01). Of hospital survivors, 98% have been followed for a mean of 29 months. The estimated 5-year survival (+/- SEM) of all patients was 71 +/- 4.5%, and for hospital survivors, 80 +/- 4.5%. The most important predictor of adverse survival was an ejection fraction less than 0.50. Seventy-nine percent are angina-free, and 89% are in NYHA classes I and II. The majority of patients felt that they were improved by surgery. We conclude that CABG in patients 80 years or older, although associated with increased operative risk, gives excellent relief of symptoms and good 5-year survival. Patients should not be denied CABG because of age alone. PMID- 2225410 TI - Internal mammary artery and saphenous vein graft patency. Effects of aspirin. AB - As part of two Department of Veterans Affairs Cooperative Trials, we obtained angiographic patency data for internal mammary artery (IMA) and saphenous vein grafts to the left anterior descending (LAD) coronary artery at 1 year after coronary artery bypass surgery. Patients received either aspirin 325 mg q.d., aspirin 325 mg t.i.d., aspirin 325 mg and dipyridamole 75 mg t.i.d., or placebo. Aspirin was initiated either 12 hours before or 6 hours after operation. Patients were stratified preoperatively for extent of disease and randomized to the therapies outlined above. There was no randomization to IMA versus saphenous vein grafts to the LAD. When the patients taking placebo were compared with those taking aspirin, there were no differences in the IMA (100.0% versus 92.1%, p = 0.385) or vein graft (88.8% versus 90.4%, p = 0.675) patency rates. The patency rate, irrespective of treatment, for all IMA grafts was 92.8% (220 of 237) versus 90.1% (345 of 383) for all vein grafts to the LAD (p = 0.309). Thus, both the IMA and vein grafts had excellent patency rates at 1 year. Aspirin did not alter this at 1 year, and there were no differences between IMA and vein graft patency to the LAD. PMID- 2225411 TI - Dissection of the aorta and dissecting aortic aneurysms. Improving early and long term surgical results. AB - We report the improving surgical results in a consecutive series of 690 patients referred to one of us (E.S.C.) for aortic dissection between December 1956 and September 1989, a substantial portion of whom had dissection as a complication of either previous aortic (n = 113, 16) or previous cardiac (n = 54, 8%) operation. Our initial operation of choice in patients requiring multiple operations in this group of 690 patients was based on the most life-threatening or symptomatic aortic segment involved, which was ascending aorta and/or aortic arch (Asc/Arch) in 301 (44%) patients, descending thoracic aorta (Desc) in 195 (28%) patients, and thoracoabdominal aorta (TaA) in 194 (28%) patients. As detailed below, considerable improvement occurred in the 30-day survival rates over time, particularly for acute dissection: [table; see text] The independent determinants of both early and long-term mortality were identified. Independent determinants of late fatal rupture, reoperation, and neuromuscular dysfunction for distal dissectors were also identified. In our experience, continued aggressive surgical intervention for aortic dissection with modern operative techniques has resulted in markedly improved 30-day operative survival (approaching 95% including those patients with acute dissection) and significant improvement in late results. PMID- 2225412 TI - Relative risks of left ventricular aneurysmectomy in patients with akinetic scars versus true dyskinetic aneurysms. AB - From 1971 to 1988, 303 patients underwent left ventricular aneurysm resection. We analyzed preoperative and procedure-related variables to ascertain risk factors for surgery. A distinction was made between akinetic and dyskinetic aneurysms to assess potential relation with postoperative outcome. Indications for surgery were arrhythmia in 20 patients, congestive heart failure in 81, angina in 133, congestive heart failure and angina in 42, and other combinations in the remaining 27 patients. The left ventricular aneurysm was dyskinetic in 180 patients and akinetic in 121. Risk factors and surgical procedures were similar in both groups. Left ventricular ejection fraction was less than or equal to 30% in 98 patients. Coronary bypass grafting was performed in 269 patients, with an average of 2.3 grafts per patient. Mitral valve replacement, the most common concomitant procedure, was performed in 16 patients. Intra-aortic balloon assist was required postoperatively in 47 patients. Overall operative mortality was 13% (38 patients) and was due to low cardiac output in 23 patients and arrhythmia in 12 patients. Univariate and multivariate analyses related early mortality to New York Heart Association functional classification of heart failure, the predominant indications of arrhythmia or congestive heart failure, left ventricular ejection fraction less than or equal to 30%, the need for intra aortic balloon support, and the excision of an akinetic (18%) rather than dyskinetic (8%) left ventricular aneurysm. Over a follow-up period averaging nearly 5 years, the actuarial survival at 5 years was 63% in the dyskinetic group and 51% in the akinetic group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225413 TI - Latissimus dorsi cardiomyoplasty in the treatment of patients with dilated cardiomyopathy. AB - Stimulated skeletal muscle grafts have been proposed as a means to reinforce ventricular wall in the treatment of severe myocardial failure. Latissimus dorsi cardiomyoplasty was performed in 11 patients with advanced heart failure due to cardiomyopathy who were in New York Heart Association (NYHA) class III or IV despite maximal medical therapy. There were no operative deaths. Eight patients were followed for a mean of 10.8 months. Two patients remain in muscle conditioning protocol. One patient died with latissimus dorsi ischemia and congestive heart failure. Four of the eight patients in long-term follow-up are in NYHA class I, three in class II, and one in class III. At 3 months of follow up, rest radioisotopic left ventricular ejection fraction increased from 20.5 +/- 3.6% to 26.8 +/- 8.1% (p less than 0.01). Doppler-echocardiography demonstrated that left ventricular segmental wall shortening improved from 11.3 +/- 2.5% to 16.5 +/- 3.9% (p less than 0.01) and left ventricular stroke volume from 22.9 +/- 4.6 to 33.1 +/- 10 ml (p less than 0.01). Cardiopulmonary exercise test showed that maximal oxygen consumption during treadmill test increased from 14.8 +/- 3.7 to 18.2 +/- 3.3 ml/kg.min (p less than 0.05). At 6 months of follow-up, all the above values remained essentially unchanged. Furthermore, nonsustained ventricular tachycardia was abolished without specific medical therapy in four patients. Thus, cardiomyoplasty improves left ventricular function, reverses congestive heart failure, and may improve long-term survival in severe cardiomyopathies. PMID- 2225414 TI - Long-term preservation of baboon hearts. Effects of hypothermic ischemic and cardioplegic arrest on high-energy phosphate content. AB - Baboon hearts were preserved ex vivo after hypothermic ischemic or cardioplegic arrest and were stored cold (0.5 degrees C) for 24 hours. Ischemic arrest was induced on cardiopulmonary bypass after general cooling to 25 degrees C. Cardioplegic arrest was induced using either a hyperkalemic standard cardioplegic solution National Institutes of Health [( NIH] solution) or the recently developed University of Wisconsin (UW) organ preservation solution. ATP and catabolites were assessed in serial transmural biopsies. Cardioplegia significantly delayed the breakdown of ATP during storage. After infusion of the adenosine-supplemented UW solution, myocardial content of adenosine was high as compared with that in NIH-arrested hearts (9.12 versus 0.01 mumol.g-1 dry wt). During cold storage, however, adenosine converted to inosine in spite of profound hypothermia. This renders unlikely the potential of fast resynthesis of ATP out of the supplemented nucleoside pool after reoxygenation. PMID- 2225415 TI - Progressive coronary luminal narrowing after cardiac transplantation. AB - Accelerated coronary disease is a major factor limiting long-term survival in cardiac transplant recipients. Coronary angiography was obtained a mean of 5.1 weeks posttransplantation and annually thereafter. Replicate projections recorded after nitroglycerine administration were quantitated using computer-assisted edge detection. Five hundred and fifteen coronary segments in 25 patients having 1 year follow-up and 353 segments in 18 patients reaching 2-year follow-up were compared with baseline angiograms. Significant change was defined as +/- 0.10 mm, equal to 3.8% change in diameter based on three standard deviations obtained from estimation of measurement error. Mean coronary diameter fell from 2.44 +/- 0.26 mm at baseline to 2.21 +/- 0.34 mm (p less than 0.001) at 1-year follow-up. This rate of diameter decline was 20-fold more rapid during the initial posttransplantation year than the rate of change of visually normal segments in nontransplant patients with coronary atherosclerosis elsewhere. There was no significant drop in mean diameter between the first and second year in those patients who had second-year studies. Decrease in absolute diameter for vessels greater than 2.9 mm significantly exceeded diameter reduction for smaller vessels but did not differ when considered as a ratio of vessel diameter. In 21 of 25 patients, mean coronary diameter reduction exceeded the three-standard deviation threshold at their last angiogram, but only two of these patients had visually detectable transplant coronary disease. PMID- 2225416 TI - Five-year experience with triple-drug immunosuppressive therapy in cardiac transplantation. AB - Although triple-drug immunosuppression with a combination of cyclosporine, prednisone, and azathioprine has been shown to improve short-term survival after cardiac transplantation, its long-term effects still are unknown. From December 1983 through December 1988, all patients (N = 139) who underwent orthotopic cardiac transplant at our institution received triple-drug immunosuppressant therapy. Follow-up averaged 32.2 +/- 15.8 months. Twenty-one patients died; 134 survived more than 30 days. Actuarial survival was 92% at 1 year, 85% at 3 years, and 78% at 5 years. Twenty-five episodes of acute graft rejection were diagnosed in 21 of the 139 recipients (0.18 episode per patient). In patients, the incidence of infection was 0.82 episode; 72% of infections were viral, with 10% due to cytomegalovirus. The incidence of coronary artery disease was 10% at 1 year, 25% at 3 years, and 36% at 5 years. Coronary artery disease was responsible for 60% of late deaths. Arterial hypertension developed in 81% of patients, despite relatively well-maintained renal function (serum creatinine, 1.7 +/- 0.3 mg/dl). Skeletal complications occurred in 15.8% and lymphoma in 1.4% of recipients. Complete long-term rehabilitation was achieved in all but two of the surviving patients. These data support the short- and long-term effectiveness of triple-drug therapy. This regimen reduces the incidence of rejection, infection, and lymphoma, as well as the degree of renal failure. However, the incidence of posttransplant coronary artery disease has not been reduced, and graft atherosclerosis represents the major cause of late graft failure and death. PMID- 2225417 TI - Low-dose lovastatin safely lowers cholesterol after cardiac transplantation. AB - Hypercholesterolemia occurs in many cardiac transplant patients and may aggravate graft coronary arteriopathy as well as contributing to peripheral vascular disease. Lovastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase, in doses of 40-80 mg/day effectively lowers cholesterol in the general cardiac population but has been associated with rhabdomyolysis in cardiac transplant recipients. To determine whether lower doses of lovastatin would be effective and safe for lowering cholesterol after cardiac transplantation, 44 patients with blood cholesterol greater than 200 mg/dl at least 6 months after cardiac transplantation received 10-20 mg lovastatin daily. In addition, lovastatin enzyme inhibitor level was assayed in six patients to determine whether metabolism of the drug was abnormal. Lovastatin decreased total cholesterol by 28% from 282 +/- 54 to 208 +/- 62 mg/dl (p less than 0.005), primarily because of reduction in the low-density lipoprotein fractions, and was well-tolerated without any symptoms or abnormal creatine phosphokinase levels in 43 of 44 patients. One patient developed rhabdomyolysis and reversible renal failure when lovastatin was increased to 40 mg daily. Enzyme inhibitor levels in the six transplant patients were 4.2-7.8 times higher than those measured in normal volunteers. Low-dose lovastatin effectively lowers cholesterol in patients after transplantation, but metabolism is altered, perhaps by cyclosporine. Monitoring of enzyme inhibitor levels may be required to allow safe administration of this drug to cardiac transplant recipients. PMID- 2225418 TI - Mechanical myocardial actuation during ventricular fibrillation improves tolerance to ischemia compared with cardiopulmonary bypass. AB - Direct mechanical ventricular actuation (DMVA) is a unique non-blood-contacting biventricular assist device that provides circulatory support during ventricular fibrillation without demonstrating adverse effects on the myocardium. The purpose of this study was to assess the preservation of myocardial energy stores and myocardial responses to ischemia after circulatory support during ventricular fibrillation with direct mechanical ventricular actuation versus cardiopulmonary bypass. Twenty adult mongrel dogs were randomized to receive circulatory support with either cardiopulmonary bypass or direct mechanical ventricular actuation. After 4 hours of ventricular fibrillation, hearts were defibrillated and left ventricular transmural biopsies were obtained. Hearts were then excised and subjected to 90 minutes of normothermic total ischemia. Serial biopsies were obtained at 15-minute intervals to determine regional depletion of high energy phosphates. The time-to-peak ischemic contracture was recorded by using needle tipped Millar catheters placed in the left ventricular endocardium, epicardium, septum, and right ventricle. Time-to-peak ischemic contracture of the endocardium (62.6 +/- 1.4 vs. 58.8 +/- 1.0 minutes, p less than 0.05) and septum (61.1 +/- 6.9 vs. 46.9 +/- 6.2 minutes, p less than 0.004) were significantly prolonged after direct mechanical ventricular actuation versus cardiopulmonary bypass, respectively. Similar trends were noted in the epicardium and right ventricular regions; however, these differences were not statistically significant. Left ventricular adenosine triphosphate (ATP) levels were better preserved after direct mechanical ventricular actuation (22 +/- 1.5 mumols/g dry wt) compared with cardiopulmonary bypass (17 +/- 1.9 mumols/g dry wt). The depletion of left ventricular endocardium ATP during normothermic ischemia was significantly delayed after direct mechanical ventricular actuation compared with cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225419 TI - Late complications in pediatric cardiac transplant recipients. AB - Late complications occurring more than 3 months after cardiac transplantation were analyzed in 29 pediatric patients in whom 31 cardiac transplantations were performed. Age at transplantation ranged from 3 months to 18 years (mean, 11.3 years) with follow-up ranging from 3.5 to 54 months (mean, 21.6 months). There were seven late deaths and two patients with retransplantations. Of nine grafts lost, eight were due to acute rejection, and one was due to coronary disease. Four of the grafts lost were secondary to patient noncompliance with prescribed immunosuppression. The mean rejection frequency more than 1 year after cardiac transplantation was significantly higher in those patients who eventually lost their grafts; however, these patients could not be distinguished by their rejection frequency in the first year. Eight patients had coronary disease, with five diagnosed at autopsy, two at cardiac retransplantation, and one by angiography. All eight patients were on double immunosuppression; none of the 19 patients on triple therapy had coronary disease with similar follow-up. There were 12 serious infections in eight patients (four associated with OKT3) with no deaths. Five patients had arrhythmias requiring treatment including two pacemakers; four of the five were associated with rejection episodes. Twelve of 29 patients developed early hypertension, and five developed late hypertension (greater than 1 year). There were two malignancies; one patient with Hodgkin's lymphoma was cured with chemotherapy, and one patient with histiocytic lymphoma was discovered at autopsy. Two patients had cholecystectomies, and five patients required laser gingivectomies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225421 TI - High-risk reparative surgery. A neglected alternative to heart transplantation. AB - The selection of patients for either high-risk reparative operations on the heart or for transplantation has become increasingly difficult as a result of improved results with both modalities. A retrospective review was done of patients referred for heart transplantation who were not considered candidates for conventional cardiac surgery, yet instead underwent reparative procedures rather than transplantation. Of 23 adult patients referred during a 7-year period, 18 had coronary artery disease, and five had valvular heart disease. All had New York Heart Association class IV symptoms. Preoperative left ventricular ejection fractions were in the range 0.08-0.63 (mean, 0.28). Ten of 18 patients with coronary artery disease required insertion of an intra-aortic balloon pump for hemodynamic support perioperatively. Seven patients had primary coronary artery bypass grafts, and 10 had reoperative coronary bypass procedures. One patient had a left ventricular aneurysmectomy, and one had endocardial stripping in addition to myocardial revascularization procedures. Of the patients with valvular disease, three had aortic valve replacement, of which two were reoperations, and two others had mitral valve replacements with tricuspid annuloplasties. With a mean follow-up of 25 months, 1-, 3-, 12-, and 24-month actuarial survival rates were 91%, 87%, 82%, and 76%, respectively. One patient who underwent aortic valve replacement in this study successfully received heart transplantation 19 months postoperatively. These results compare favorably with the current results for patients undergoing first-graft heart transplantation. All survivors enjoy New York Heart Association class I or II functional capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225420 TI - The changing clinical spectrum of thromboangiitis obliterans (Buerger's disease). AB - Between 1970 and 1987, 112 patients were diagnosed as having thromboangiitis obliterans (TAO). The age was 42 +/- 11 years (mean +/- SD; range, 20-75 years); 23% were women, and 7% were more than 60 years old when they were first diagnosed. Ischemic ulcerations were present in 85 (76%) patients: 24 (28%) patients with upper-extremity, 39 (46%) patients with lower-extremity, and 22 (26%) patients with both upper- and lower-extremity lesions. Ninety-one (81%) patients had rest pain, 49 (44%) patients had Raynaud's phenomenon, and 43 (38%) patients had superficial thrombophlebitis. We were able to follow up 89 of the 112 (79%) patients for 1-460 months (mean follow-up time, 91.6 +/- 84 months). Sixty-five (73%) patients had no amputations, while 24 (27%) had one or more of the following amputations: finger, six (15%) patients; toe, 13 (33%) patients; transmetatarsal, four (10%) patients; below knee, 14 (36%) patients; and above knee, two (5%) patients. Forty-three (48%) patients stopped smoking for a mean of 80 +/- 105 months (median, 46.5 months; range, 1-420 months), and only two (5%) patients had amputations after they stopped smoking, while 22 (42%) patients had amputations while continuing to smoke (p less than 0.0001). The spectrum of patients with TAO is changing in that the male-to-female ratio is decreasing (3:1), more older patients are being diagnosed, and upper-extremity involvement is commonly present. In the 48% of patients who stopped smoking, amputations and continued disease activity were uncommon. PMID- 2225422 TI - Optimal temperature for preservation of donor myocardium. AB - The ideal method for the preservation of donor hearts for transplantation is unclear. To assess the optimal temperature for donor myocardium preservation, the recovery of isolated canine hearts (n = 20) exposed to 4 hours of either standard ice-chest hypothermia (0-4 degrees C) or constant moderate hypothermia (12 degrees C) were compared. Functional and metabolic data were acquired before hypothermia and every 30 minutes during 3 hours of reperfusion with oxygenated blood. Mean end-systolic pressure-volume slopes were 2.11 +/- 0.06 and 2.09 +/- 0.06 mm Hg/ml for ice-chest hypothermia and constant moderate hypothermia, respectively (p = NS), which were unchanged from control. All y intercepts during reperfusion were decreased compared with control (p = 0.002) without any differences between groups. End-diastolic pressures were greater than control throughout the reperfusion period for both groups (p = 0.02), but there was a difference in change of end-diastolic pressures with time between groups (p = 0.04). Dry/wet ratios were similar after preservation and reperfusion in both groups. ATP recovered to control levels during reperfusion for both groups although energy charge ratios were greater for hearts exposed to constant moderate hypothermia (p = 0.007). These data indicate that intracellular energy stores are well maintained by preservation using either technique. Changes in function appear to be related to altered compliance irrespective of preservation temperature. These data suggest that a wide range of temperatures may be acceptable for donor heart preservation. PMID- 2225423 TI - Bradyarrhythmia after heart transplantation. Incidence, time course, and outcome. AB - From June 1980 to April 1989, 72 of 401 (18%) adult recipients of orthotopic heart transplantation developed prolonged (greater than 24 hours) bradyarrhythmias (less than 60 beats/min) within 5 days after transplantation. Junctional bradycardia occurred in 50 (69%) recipients, sinus bradycardia in 18 (25%), and slow ventricular response during atrial fibrillation in four (6%). Fifty-five of 72 (76%) patients had bradyarrhythmias of less than 20 days' duration (less than 7 days, 50 patients; 7-20 days, five patients). Fifty patients returned to sinus rhythm (greater than 60 beats/min) by the time of discharge. Five patients expired within 20 days. Seventeen of 72 (24%) patients had bradyarrhythmia for more than 20 days, which was symptomatic in 11. All 17 patients (junctional bradycardia, 13 patients; sinus bradycardia, four patients) received a permanent pacemaker within 40 days after transplantation. Between 1 and 12 months (mean, 4 +/- 3 months) after pacemaker implantation, 12 patients recovered sinus rhythm (greater than 70 beats/min). The other five patients had intrinsic rates of 32-57 beats/min (mean, 48 +/- 10 beats/min) during 1-9 months (mean, 4 +/- 3 months) of follow-up. The donor ischemic time in bradyarrhythmia patients was 202 +/- 34 minutes, which was significantly longer (p less than 0.01) than the 173 +/- 43 minutes for those patients without bradyarrhythmia. Conclusively, the incidence of posttransplantation bradyarrhythmia is relatively high. It is usually temporary, however, even in patients with a prolonged duration of bradyarrhythmia. A relation appears to exist between donor ischemic time and the incidence of bradyarrhythmia. PMID- 2225424 TI - Factors affecting survival in total artificial heart recipients before transplantation. AB - To identify factors affecting the successful bridge to transplantation, experience with 32 recipients of the Jarvik-7 artificial heart was reviewed. Between patients with and without a successful bridge, there were no significant differences in preoperative hepatorenal function or postoperative hemodynamics, but there were significant differences in body size. When recipients were divided according to body surface areas of less than or greater than 1.8 m2, the smaller patients more frequently developed respirator dependence (73% vs. 18%, p less than 0.01), renal failure (53% vs. 18%, p less than 0.05), and hepatic failure and sepsis, resulting in less frequent qualification for transplantation (20% vs. 65%, p less than 0.05). There were no successful bridge operations in seven patients with body surface areas of less than 1.7 m2, and only one success in nine patients who were less than 170 cm in height, despite use of a smaller stroke volume model. The smaller patients had poorer ventricular filling, which was largely compensated for by the drive controls set for significantly longer diastole and higher vacuum, resulting in similar hemodynamics between the groups. The results suggest that device fitting as manifested by body size is an important factor affecting major organ recovery and subsequent transplantation in recipients of the Jarvik-7 artificial heart. A paracorporeal device may be advisable for patients with body surface areas of less than 1.8 m2 or who were less than 175 cm in height until an even smaller model with a better fit in the thorax becomes available. PMID- 2225425 TI - Right ventricular function and metabolism. AB - Right ventricular protection may be limited with current methods of cardioplegic delivery. Sensitive measurements of right and left ventricular function and metabolism were made in 30 patients undergoing elective coronary artery bypass surgery with cold cardioplegic arrest. Myocardial adenine nucleotide concentrations decreased with cardioplegia and reperfusion in both the right and left ventricles despite adequate levels of precursors, suggesting perioperative mitochondrial dysfunction. Postoperatively, right and left ventricular pressures were measured with micromanometer catheters and volumes were measured by nuclear ventriculography. Right and left ventricular systolic elastance was calculated by the isochronic method and by the end-systolic method. Both methods provided sensitive indexes of end-systolic elastance. This study demonstrated that right ventricular function and metabolism can be evaluated by methods analogous to methods used in the left ventricle. These results suggest that right ventricular functional and metabolic recovery are delayed despite apparently adequate myocardial protection. Sensitive measurements may permit improved assessment of alternative methods of right ventricular protection. PMID- 2225426 TI - Is adenosine 5'-triphosphate derangement or free-radical-mediated injury the major cause of ventricular dysfunction during reperfusion? Role of adenine nucleoside transport in myocardial reperfusion injury. AB - The aim of this study was to determine the dual role of ATP as an energy substrate and as a major source of oxygen-derived free-radical-mediated reperfusion injury by using adenine nucleoside blocker, p-nitrobenzylthioinosine (NBMPR), and adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA). In a randomized study, 16 dogs were instrumented with minor-axis LTZ piezoelectric crystals and intraventricular pressure transducers to monitor, off bypass, left ventricular performance by using a sensitive and load-independent index of contractility (slope of the stroke work-end-diastolic length relation). Hearts were subjected to 60 minutes of normothermic global ischemia and 120 minutes of reperfusion. Normal saline without (Group 1, n = 8) or with (Group 2, n = 8) NBMPR and EHNA was infused in three boluses into the cardiopulmonary bypass reservoir before ischemia and reperfusion. Transmural serial biopsies were obtained before and during ischemia and reperfusion and analyzed for myocardial adenine nucleotide pool intermediates by using high-performance liquid chromatography. In the control group, three hearts developed ischemic contracture and another three hearts exhibited cardiogenic shock during reperfusion. In the EHNA/NBMPR-treated group, left ventricular performance recovered within 30 minutes of reperfusion (p less than 0.05 vs. control). Myocardial ATP was depleted to 20% of normal in both groups by the end of ischemia (p less than 0.05). Intramyocardial adenosine in the EHNA/NBMPR-treated group was 12-fold greater (15.09 +/- 1.6 nmol/mg protein) than the control group at the end of the ischemic period (p less than 0.05). Inosine was about fourfold higher in the control group (19.07 +/- 1.50 nmol/mg protein) compared with the drug-treated group (p less than 0.05). During reperfusion, myocardial ATP levels increased to approximately 50% of normal in the EHNA/NBMPR group while remaining depressed (20% of normal) in the control group. Thus, despite the dramatic loss of myocardial ATP during ischemia, complete recovery of ventricular performance and significant repletion of ATP during reperfusion were observed when adenosine transport and deamination were modulated during ischemia and reperfusion. These results suggest that 1) the myocardium may have more ATP than is needed for basic cardiac functions and 2) washout of ATP diffusible catabolites is detrimental to ventricular performance during reperfusion. Specific blockade of nucleoside transport resulted in complete functional recovery despite low but critical ATP levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2225427 TI - Prolonged cardiac preservation. Evaluation of the University of Wisconsin preservation solution by comparison with the St. Thomas' Hospital cardioplegic solutions in the rat. AB - The University of Wisconsin solution differs from other types of solutions used for organ preservation because it contains high-energy phosphate precursors (adenosine and phosphate), impermeants (lactobionate and raffinose), an oncotic agent (pentafraction), and antioxidants (allopurinol and glutathione). These components have the potential to enhance the preservation of ATP, reduce intracellular and extracellular edema, and attenuate free-radical-mediated injury. The University of Wisconsin solution has been demonstrated to enhance and extend the preservation of the liver, pancreas, and kidney, but its potential role in the heart remains unproven. We have evaluated the University of Wisconsin solution (Du Pont) by comparing it with the St. Thomas' Hospital cardioplegic solutions No. 1 and No. 2 (Plegisol), which are used in Europe and the United States for routine cardiac surgery and transplantation. For each solution, 10 isolated working rat hearts were arrested by 10 ml of the solution (at 4 degrees C) and then maintained immersed in the same solution for 4 hours at 4 degrees C. Mean recovery of functional indexes (expressed as a percentage of their preischemic control values) after use of the University of Wisconsin solution were as follows: peak aortic pressure, 90.6 +/- 1.0; dP/dt, 71.5 +/- 5.5; aortic flow, 81.6 +/- 4.7; coronary flow, 87.5 +/- 3.5; and cardiac output, 82.6 +/- 3.5. In contrast, the mean recoveries after St. Thomas' Hospital solution No. 1 were as follows: peak aortic pressure, 82.8 +/- 1.3; dP/dt, 49.7 +/- 3.0; aortic flow, 58.4 +/- 5.3; coronary flow, 79.6 +/- 5.9; and cardiac output, 63.0 +/- 4.9. In contrast still, mean recoveries after St. Thomas' Hospital solution No. 2 were as follows: peak aortic pressure, 83.1 +/- 1.2; dP/dt, 40.7 +/- 6.1; aortic flow, 37.0 +/- 5.1; coronary flow, 65.8 +/- 3.6; and cardiac output, 43.1 +/- 5.6. The recovery of all indexes were significantly superior (p less than 0.005) after preservation with University of Wisconsin solution compared with either of the St. Thomas' Hospital solutions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225429 TI - Identification of patients at greatest risk for developing major complications at cardiac surgery. AB - As part of a prospective program to use risk-adjusted outcome (operative mortality and morbidity) as a measure of quality of care, we have analyzed perioperative complication data in 10,634 patients representing 73% of all patients undergoing cardiac surgery requiring cardiopulmonary bypass at Veterans Administration medical centers between April 1, 1987, and March 31, 1989. One or more complications occurred in 15% of patients undergoing coronary artery bypass grafting, and in 24% of patients undergoing valve and other cardiac surgery. Patients experiencing one or more complications had an eightfold to 10-fold increase in operative mortality compared with patients with no perioperative complications. The most frequent complication was requirement for mechanical ventilation for at least 48 hours occurring in 8% of patients undergoing coronary artery bypass and in 15% of patients undergoing valve and other cardiac surgery; 24-25% of these patients died within 30 days of surgery or as a direct result of a surgical complication. Previous heart surgery was a strong predictor of development of one or more complications in both groups of patients, being associated with an adjusted relative risk of 1.6-2.0. Other important predictors in both surgical groups were surgical priority, older age, peripheral vascular disease, and higher serum creatinine. Although a number of preoperative risk factors could be identified for the development of renal failure, low cardiac output, and requirement for prolonged mechanical support, few risk factors could be identified for the development of mediastinitis and reoperation for bleeding. This observation suggests that mediastinitis and reoperation for bleeding are more likely the result of technical factors rather than patient-related risk factors. PMID- 2225428 TI - Efficacy of recombinant-derived human superoxide dismutase on porcine left ventricular contractility after normothermic global myocardial ischemia and hypothermic cardioplegic arrest. AB - A porcine model of normothermic global ischemia (40 minutes) followed by systemic cooling to 25 degrees C with 4 degrees C crystalloid cardioplegic arrest (90 minutes) was used to assess the efficacy of recombinant-derived human superoxide dismutase (r-HSOD) on postreperfusion left ventricular function while on cardiopulmonary bypass. Isovolumic hemodynamic function was monitored, and adenine nucleotide pool was measured in myocardial biopsy specimens and coronary sinus effluent. The treatment group of pigs (n = 7) received 15 mg/kg r-HSOD immediately before warm reperfusion, both left ventricular peak systolic pressure and developed pressure were significantly better in the r-HSOD group of pigs (p less than 0.05 vs. placebo). This improvement persisted at 60 minutes of reperfusion (p less than 0.05 vs. placebo). Myocardial ATP and total adenine nucleotides did not differ, nor did adenine nucleotide catabolites in the coronary sinus effluent differ between treatment groups of pigs. The exception to this was the nucleotide catabolite inosine, which was significantly elevated in coronary sinus effluent of pigs treated with r-HSOD at 30 minutes of reperfusion (p less than 0.05 vs. placebo). In this model of global ischemia and reperfusion, a recombinant-derived human free-radical scavenger provides significant protection of systolic but not diastolic function. Values for myocardial ATP and total adenine nucleotide content suggest that the improvement in mechanical function during reperfusion is not due to enhanced preservation of myocardial bioenergetics. PMID- 2225430 TI - Iron chelation by deferoxamine inhibits lipid peroxidation during cardiopulmonary bypass in humans. AB - Iron catalysis is involved in oxygen-derived free radical generation and subsequent lipid peroxidation, which have been reported to occur during cardiopulmonary bypass in humans. We assessed the effects of the iron chelator deferoxamine on the susceptibility of circulating low density lipoproteins (LDLs) to induced peroxidation in 20 adult patients (10 controls and 10 treated) undergoing cardiopulmonary bypass for coronary or valve procedures. Deferoxamine was given both intravenously (30 mg/kg body wt, starting 30 minutes before bypass and extending for the next 4 hours) and as an additive to the cardioplegic solution (250 mg/l). Blood samples were taken from both atria before and immediately after the end of cardiopulmonary bypass. Plasma lipid peroxidation was assessed by measuring spectrophotometrically the thiobarbituric acid reactive substances (TBARS) content of selectively isolated LDLs after their exposure to a peroxidizing agent. Before cardiopulmonary bypass, the right and left atrial blood values of LDL-TBARS were not significantly different between the two groups. Cardiopulmonary bypass resulted in a lipid peroxidation of significantly greater magnitude in control than in treated patients. Postbypass right atrial values for LDL-TBARS (expressed in mumol/mmol LDL-phospholipids) were 45.7 +/- 17.2 (mean +/- SEM) in control patients and 6.9 +/- 2.9 in treated patients (p less than 0.02), whereas in the left atrial blood, LDL-TBARS yielded values of 62.7 +/- 20.5 and 10.3 +/- 3.9, respectively (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225431 TI - Adverse hemodynamic effects and echocardiographic consequences of pericardial closure soon after sternotomy and pericardiotomy. AB - The acute hemodynamic and echocardiographic effects of pericardial closure on cardiac function were studied in 11 pigs during steady-state anesthesia and ventilation. Observations were made after sternotomy, both while the pericardium was open and after it had been closed, and then after closure of the chest, after the pericardium had been reopened by removing the pericardial suture through the chest wall. In five pigs, further observations were made when a suture was tightened to close the pericardium while the chest remained closed. Closure of the pericardium when the chest was open reduced cardiac output by 14% and mean stroke volume by 19% (both p less than 0.05). Systemic vascular resistance increased by 15% when the pericardium was closed while the chest was open (NS), and increased by 19% when it was closed while the chest was closed (p less than 0.05). Heart rate did not change significantly, and the systemic blood pressure was maintained (-8%, NS). All these effects were reversed by opening the pericardium. Intrathoracic epicardial echocardiographic monitoring of the left ventricle showed that its end-diastolic dimension increased (by 11%, p less than 0.05) when the pericardium was opened. After chest closure, paradoxical motion of the interventricular septum was consistently demonstrated only during ventilation, and it was not related to whether or not the pericardium was open. This study suggests that cardiac function may be impaired by pericardial closure after cardiac surgery because of some degree of constriction of the heart chambers, although acute circulatory responses compensate for the mild decrease in stroke volume. Monitoring of blood pressure alone cannot document the subtle circulatory changes induced by pericardial closure, and therefore it is not a reliable guide to decisions of whether to close the pericardium or leave it open in individual patients. PMID- 2225432 TI - Diabetic patients have abnormal cerebral autoregulation during cardiopulmonary bypass. AB - We tested the hypothesis that insulin-dependent diabetic patients with coronary artery bypass graft surgery experience altered coupling of cerebral blood flow and oxygen consumption. In a study of 23 patients (11 diabetics and 12 age matched controls), cerebral blood flow was measured using 133Xe clearance during nonpulsatile, alpha-stat blood gas managed cardiopulmonary bypass at the conditions of hypothermia and normothermia. In diabetic patients, the cerebral blood flow at 26.6 +/- 2.42 degrees C was 25.3 +/- 14.34 ml/100 g/min and at 36.9 +/- 0.58 degrees C it was 27.3 +/- 7.40 ml/100 g/min (p = NS). The control patients increased cerebral blood flow from 20.7 +/- 6.78 ml/100 g/min at 28.4 +/ 2.81 degrees C to 37.6 +/- 8.81 ml/100 g/min at 36.5 +/- 0.45 degrees C (p less than or equal to 0.005). The oxygen consumption was calculated from jugular bulb effluent and increased from hypothermic values of 0.52 +/- 0.20 ml/100 g/min in diabetics to 1.26 +/- 0.28 ml/100 g/min (p = 0.001) at normothermia and rose from 0.60 +/- 0.27 to 1.49 +/- 0.35 ml/100 g/min (p = 0.0005) in the controls. Thus, despite temperature-mediated changes in oxygen consumption, diabetic patients did not increase cerebral blood flow as metabolism increased. Arteriovenous oxygen saturation gradients and oxygen extraction across the brain were calculated from arterial and jugular bulb blood samples. The increase in arteriovenous oxygen difference between temperature conditions in diabetic patients and controls was significantly different (p = 0.01). These data reveal that diabetic patients lose cerebral autoregulation during cardiopulmonary bypass and compensate for an imbalance in adequate oxygen delivery by increasing oxygen extraction. PMID- 2225433 TI - Treatment with desmopressin acetate in routine coronary artery bypass surgery to improve postoperative hemostasis. AB - Desmopressin acetate (DDAVP) has been shown to decrease blood loss and transfusions in complex cardiac operations with long extracorporeal times. Its use in routine cardiac valve operations has been shown not to be beneficial, but its role in routine coronary artery bypass grafting operations has not been defined. We examined the effect of DDAVP in a prospective study of 60 patients undergoing uncomplicated primary coronary artery bypass grafting operations. Thirty consecutive patients received DDAVP (0.3 micrograms/kg) after cardiopulmonary bypass and were compared with 30 consecutive patients who did not receive DDAVP. No significant differences were seen in 12-hour mediastinal blood loss (465 +/- 207 ml with DDAVP versus 511 +/- 221 ml without DDAVP) or 12-24 hour mediastinal blood loss (236 +/- 127 ml with DDAVP versus 260 +/- 112 ml without DDAVP). Transfusion of blood products were similar for both groups. Platelet aggregometry at intraoperative and postoperative time points using ADP, collagen, and ristocetin was not significantly different from baseline values in either group. In a subgroup of patients with poor initial ristocetin-induced platelet aggregometry, a significant increase (p less than 0.05) in ristocetin induced platelet aggregometry was seen postoperatively only in those patients who had received DDAVP. A decrease in blood loss and transfusions, however, was not demonstrable. In those patients who had been on aspirin or nonsteroidal anti inflammatory drugs preoperatively, DDAVP did not improve mediastinal blood loss or transfusion needs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225434 TI - Neurological and ophthalmological phenomena after aortic conduit surgery. AB - Transient neurological and visual signs have been observed in some patients after valved conduit replacement of the aortic valve and ascending aorta. Twenty-seven patients having valved conduit replacement between February 1982 and October 1988 were compared with 21 patients having combined aortic valve replacement (AVR) and ascending aorta (AA) graft replacement. Follow-up in 100% of both groups was obtained for 0.3-6.6 years (mean, 2.6 +/- 0.3 years). Among 20 surviving valved conduit patients, 10 (50.0%) experienced repetitive neurological and visual signs, including scotomata (seven), transient motor ischemic attacks (two), amaurosis fugax (four), and recurring attention lapses suggesting petit mal seizures (one). No patient with AVR + AA graft experienced any events (p = 0.004). All valved conduit and seven (53.8%) of AVR + AA graft patients were on warfarin (p = 0.0016). These events retained the same pattern although they diminished in frequency after 12 months in seven patients (70.0%) and after initiation of dipyridamole in two patients. Rehabilitation was similar in both groups: 18 of 20 (90.0%) valved conduit and 12 of 16 (75.0%) AVR + AA graft patients (p = NS). Transient, repetitive, nonprogressive neurological and ophthalmological phenomena are frequent after valved conduit replacement. The pathophysiological mechanism is unclear, but antiplatelet therapy may provide symptomatic control. PMID- 2225435 TI - Reappraisal of the mechanism for cerebrospinal fluid hypertension during aortic surgery. AB - Cerebrospinal fluid (CSF) hypertension during aortic surgery is a poorly understood, multifactorial event that may increase the risk of spinal cord injury. To assess the factors that may contribute to changes in CSF pressure during aortic surgery, measurements of ascending arterial and CSF pressures were made in 17 anesthetized mongrel dogs. Changes in CSF patterns were monitored under several conditions tested in random sequence. These included systemic hypertension produced by an infusion of phenylephrine, cross-clamping of the descending thoracic aorta, and manual, superior displacement of the transverse aortic arch (arch elevation), either alone or in conjunction with the cross clamp. Hypertension, cross-clamping, and cross-clamping combined with arch elevation all produced significant increases in ascending mean arterial pressure (204 +/- 20, 170 +/- 8, and 158 +/- 11 mm Hg, respectively, vs. 117 +/- 8 mm Hg [control]; (p less than 0.01). Small, nonsignificant increases in CSF pressure were detected in the cross-clamp group, but none were detected with hypertension alone, despite significant increases in ascending arterial blood pressure in both groups. Thus, neither arterial hypertension nor cross-clamping alone could be demonstrated directly to cause significant CSF hypertension. However, when aortic elevation (displacement) was combined with cross-clamping, the rise in CSF pressure increased to significant levels, even though the ascending arterial hypertension was least severe in this group. In contrast, arch elevation alone did not produce any significant increase in ascending arterial pressure but did produce an approximately 114% increase in CSF pressure (15.2 +/- mm Hg vs. 7.7 +/ 1 mm Hg [control]; p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225436 TI - Comparison of rigid and flexible rings for annuloplasty of the porcine mitral valve. AB - Seven rigid (Carpentier) and six flexible (Duran) annuloplasty rings were implanted in healthy pigs. First, in the intact pig, cinefluoroscopy was used to record movements of the anulus. Results were compared with data from three pigs instrumented with a continuous radiopaque marker on the anulus. Pump function of all hearts with annuloplasty rings and function of the mitral valve were studied 4-6 weeks after the operation, first in the exposed heart and then subsequently in the isolated heart in a perfusion chamber at maximal filling pressure and normal or low arterial pressure. Separation of the blood-perfused coronary circulation from the crystalline solution pumped by the left heart allowed videoendoscopy of the working valve. Flexible rings interfered less with normal movements of the mitral anulus than rigid rings and caused less impairment of filling of the basal part of the ventricle, and the unloaded stroke volume was 16% larger. For normal arterial pressures, the differences were smaller and will be difficult to detect in clinical situations. A stiff anulus was seen to be pushed underneath the aortic valve during systole, which caused a mild subvalvular obstruction. The mean diastolic pressure gradient across rigid annuloplasty rings was slightly larger than across flexible rings of the same or slightly smaller diastolic size. Rigid rings change the pattern of movement of the leaflets; the mural leaflet remains immobile throughout diastole. Although Duran rings interfere less with valvular function and filling of the basal part of the ventricle than do Carpentier rings, the differences are small and probably only of limited clinical importance. PMID- 2225437 TI - Late results with Carpentier-Edwards porcine bioprosthesis. AB - From 1977 to 1984, 429 patients underwent aortic valve replacement (AVR), and 339 underwent mitral valve replacement (MVR) with a Carpentier-Edwards bioprosthesis. Early mortality for AVR was 4.6% (isolated AVR, 1.9%) and for MVR was 5.3% (isolated MVR, 4.1%). Follow-up was 99.3% complete at a mean of 5.9 years. Actuarial event-free rates at 10 years for AVR and MVR were, respectively, 1) for structural valve deterioration, 91.4 +/- 3.2% versus 75.1 +/- 4.0% (p less than 0.01); 2) for nonstructural dysfunction, 100% versus 97.8 +/- 1.6% (p = NS); 3) for thromboembolism, 90.6 +/- 2.3% versus 87.3 +/- 2.6% (p = NS); 4) for anticoagulant-related bleeding, 95.3 +/- 1.1% versus 88.6 +/- 2.4% (p = 0.05); 5) for endocarditis, 87.8 +/- 5.7% versus 90.6 +/- 2.4% (p = NS); 6) for reoperation, 91.0 +/- 2.5% versus 74.4 +/- 3.7% (p less than 0.01); 7) for valve related mortality, 76.1 +/- 6.9% versus 71.4 +/- 5.2% (p = 0.01); 8) for permanent physical impairment, 85.0 +/- 3.0% versus 71.5 +/- 3.6% (p less than 0.01); and 9) for combined operative mortality, valve-related mortality, and reoperation, 68.7 +/- 6.4% versus 51.5 +/- 4.9% (p = 0.01). No structural valve dysfunction was observed in any AVR patient whose valve was inserted after age 70. Age at operation was the only factor that predicted structural valve deterioration (p less than 0.01). PMID- 2225438 TI - Hemodynamic comparison of Hancock and Carpentier-Edwards mitral bioprosthetic valves. AB - Although it is known that pressure gradients and calculated valve areas in bioprosthetic valves are highly flow dependent, no studies have compared bioprosthetic valve performances while adjusting for differences in flow rate. We therefore studied 75 patients undergoing mitral valve replacement who were randomized to receive either Hancock (n = 35) or Carpentier-Edwards (n = 40) bioprosthetic valves. Pressure gradients were measured using transducer-tipped catheters to record left ventricular and left atrial pressures and cardiac outputs by thermodilution. Repeated measurements were made in each patient after either pacing, fluid infusion, or pharmacological intervention to vary flow rates for a total of 239 measurements (mean, 3.2 measurements per patient). Using analyses of variance and covariance, mean valve gradients and the calculated Gorlin area were adjusted for flow rate, valve size, valve type, and interpatient differences to compare hemodynamics. Without flow and interpatient adjustment, the univariate analysis suggested higher mean gradients in the Carpentier-Edwards 29-mm valves (p = 0.038), with a trend toward higher gradients and smaller areas in the Hancock 33-mm valves (p = 0.057 and 0.059, respectively). After adjustment for flow rate and interpatient differences, however, there was no difference at any valve size in the mean pressure gradients (p = 0.13-0.89) or Gorlin valve areas (p = 0.34-0.96). Although measurements within a given patient were consistent, marked interpatient variabilities in gradients and areas were observed for identical valve types and sizes, which were as significant as flow dependent or size-dependent changes. We conclude that comparisons of valve performance should adjust for variations in flow rate and for interpatient differences with the use of repeated-measures designs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225439 TI - Importance of the mitral subvalvular apparatus for left ventricular segmental systolic mechanics. AB - The relative importance of the anterolateral (ANTLAT) and posteromedial (POSTMED) papillary muscle (PM) chordae tendineae for left ventricular (LV) segmental wall function was assessed in 12 in situ ejecting canine hearts. Pairs of piezoelectric crystals were placed in the regions subtending PM insertions and the ANTLAT LV free wall to measure wall thickness. After mitral valve replacement with complete preservation of the subvalvular apparatus, chordal attachments to either the ANTLAT PM or POSTMED PM were randomly severed using exteriorized snares, followed by subsequent division of the remaining chordae tendineae. Segmental wall function in each region was determined at each stage by segmental preload recruitable stroke work (sPRSW, slope of the segmental stroke work-end diastolic wall thickness relation). The order in which the chordae were severed was unimportant (p greater than 0.530 in all regions). When the ANTLAT PM chordae were severed first, there were significant declines in sPRSW without a change in the wall thickness intercept in both the ANTLAT (-71.0 +/- 18.3 vs. -57.7 +/- 16.8 mmHg, p less than 0.05) and POSTMED (-81.8 +/- 23.1 vs. -65.4 +/- 17.3 mmHg, p less than 0.05) PM insertion sites. No further significant reductions in sPRSW in either region were detected after severing the remaining chordal attachments to the POSTMED PM. sPRSW in the ANTLAT LV free wall decreased progressively, reaching statistical significance when both sets of chordae tendineae were divided (-88.3 +/- 14.3 vs. -74.0 +/- 15.2 mm Hg, p less than 0.05). When the POSTMED PM chordae were severed first, no significant changes in sPRSW or the wall thickness intercept in either region of PM insertion were detected. Subsequent division of the ANTLAT PM chordal attachments reduced sPRSW significantly in both the ANTLAT PM (-65.9 +/- 21.1 vs. -56.1 +/- 22.1 mm Hg, p less than 0.05) and POSTMED PM (-78.8 +/- 24.7 vs. -67.2 +/- 24.0 mm Hg, p less than 0.05) insertion sites, without a shift in the wall thickness intercept. In the ANTLAT LV free wall, sPRSW again fell progressively, achieving statistical significance only when both chordal attachments were severed (-78.6 +/- 14.8 vs. 62.2 +/- 13.7 mm Hg, p less than 0.05). In conclusion, division of the chordae tendineae resulted in a decline in segmental LV function not only in the areas subtending PM insertions but also in remote LV regions. Furthermore, the influence of the ANTLAT PM chordae predominated local LV systolic function at both PM insertion sites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2225441 TI - Recognition and treatment of cocaine abuse. PMID- 2225440 TI - The reversibility of canine vein-graft arterialization. AB - We assessed the reversibility of functional and morphological changes of arterialized vein segments by returning them to the venous circulation. Thirteen dogs underwent right carotid and femoral veno-arterial grafting. After 12 weeks, veno-arterial grafts were removed for contractility (norepinephrine [NE] and 5 hydroxytryptamine [5-HT]), luminal prostacyclin (PGI2), and morphometric analyses; the remaining segments were used as left jugular and femoral veno venous grafts. After another 12 weeks, the veno-venous grafts were harvested. To NE, veno-arterial grafts (ED50, 5.4 +/- 0.1 [-log M]) were less sensitive than control veins (ED50, 6.0 +/- 0.2) or veno-venous grafts (ED50, 6.4 +/- 0.2) but were more sensitive than control arteries (ED50, 4.0 +/- 0.1); the maximum tension of veno-arterial grafts (6.2 +/- 0.6 g) was greater than that of veins, less than that of arteries (9.8 +/- 1.0 g), and comparable with that of veno venous grafts (5.1 +/- 1.1 g). To 5-HT, veno-arterial (ED50, 7.5 +/- 0.1) and veno-venous (ED50, 7.3 +/- 0.2) grafts were more sensitive than arteries (ED50, 6.0 +/- 0.3), while the vein was unresponsive; the maximum tension of veno arterial grafts (5.0 +/- 0.7 g) was less than that of arteries (6.9 +/- 0.9 g) and greater than that of veno-venous grafts (1.4 +/- 0.3 g). PGI2 production in veins (3.6 +/- 0.8 ng/ml), veno-arterial grafts (3.9 +/- 0.8 ng/ml), and veno venous grafts (3.3 +/- 0.9 ng/ml) was comparable and less than that of arteries (6.4 +/- 0.9 ng/ml). Veno-arterial graft intimal thickness (127 +/- 8 microns) and intimal area (15.6 +/- 1.8 x 10(3) microns 2) tended to be greater than that in the veno-venous graft (113 +/- 9 microns and 12.4 +/- 1.8 x 10(3) microns 2); also, the veno-arterial graft medial area (103.0 +/- 7.3 x 10(3) microns 2) was greater than that of the veno-venous graft (80.3 +/- 6.9 x 10(3) microns 2), thereby resulting in a similar relative intimal area (13 +/- 1%). Therefore, some changes associated with arterialization, for example, adrenergic sensitivity, maximum tension to 5-HT, medial thickening, and perhaps intimal hyperplasia, reverted toward venous values when replaced in the venous environment, possibly due to variations in pressure, flow, shear stress, and/or graft preparation techniques. Luminal PGI2 was unchanged in the grafts, implying that graft contractility was not modulated by luminal PGI2. PMID- 2225442 TI - Key steps in evaluating the dizzy patient. PMID- 2225443 TI - Lipoprotein abnormalities in the progression of renal disease. AB - Chronic renal disease is a progressive process. Implicated factors include abnormalities of the clotting cascade, altered prostaglandin metabolism, increased dietary protein intake, and abnormalities of lipoprotein metabolism. Several animal models have associated increased serum concentrations of cholesterol and triglycerides with progressive decline in renal function. The mechanism(s) of lipid-associated renal injury are unknown but may relate to lipid uptake by glomerular mesangial cells, hyperviscosity secondary to the hyperlipidemia, and a direct effect of the lipids on the glomerular basement membrane. Patients with chronic renal disease have well recognized increases in serum lipid concentrations. Whether lowering these concentrations will delay or prevent progressive renal failure or renal histologic abnormalities is unknown, but studies are underway to evaluate the effect of lipid-lowering agents in patients at risk for chronic progressive renal disease. PMID- 2225444 TI - Visual compromise in the diabetic patient. PMID- 2225445 TI - Managing diabetic retinopathy. AB - Diabetic retinopathy is a leading cause of visual impairment and blindness. The disease is more likely in patients with insulin-dependent diabetes mellitus, and the incidence is higher in diabetes of long duration. In background diabetic retinopathy, the vascular changes are confined to the retina; in proliferative retinopathy, vessels grow onto the posterior vitreous surface or wedge between the retina and the vitreous. Diagnostic accuracy is more likely with an ophthalmologic consultation. A team approach between the ophthalmologist and the primary care physician is recommended for effective overall management of these patients. PMID- 2225446 TI - Electrocardiographic criteria for anterior myocardial infarction. AB - In a two-stage review, electrocardiographic patterns associated with anterior infarction were determined in 135 patients whose diagnoses were established by contrast ventriculography. The five most common findings were tested in 1,324 consecutive patients to assess sensitivity, specificity, and predictive accuracies for anterior myocardial infarction. The criteria were shown to have high positive predictive accuracy and specificity levels, and confirmed the value of the standard 12-lead electrocardiogram for detecting anterior myocardial injury. PMID- 2225447 TI - Serial electrophysiologic testing of drug therapy in supraventricular tachycardia related to accessory pathways. AB - Data are limited on the use of serial electrophysiologic testing of drug therapy in patients with supraventricular tachycardia associated with accessory pathways, including the Wolff-Parkinson-White syndrome. Twenty-four highly symptomatic patients (aged 36 +/- 11 years) with SVT related to accessory pathways underwent electrophysiologic studies to select an effective chronic oral treatment. Conventional (verapamil, propranolol, quinidine, disopyramide) and investigational (amiodarone, aprindine, propafenone) drugs were used alone and in combination if necessary. It was determined that serial electrophysiologic studies could identify potentially effective treatments in 66% of patients with reentrant SVT involving accessory pathways, and the findings were highly predictive of long-term clinical outcome. PMID- 2225448 TI - Pharmacology and use of headache medications. AB - Treatment of headache disorders is most likely to be successful when the pathophysiology of the disease is correlated with the pharmacologic actions of the available drugs. Beta blockers generally are considered first-line therapy for migraine prophylaxis, but calcium blockers also are appropriate for some patients. Antidepressants are the primary modality for treatment of tension type headaches, although they are also used for migraine prophylaxis. Mixed headache, which has features of both migraine and tension-type headache, usually requires treatment with more than one drug. Habituation to analgesics is common among patients with mixed headache. PMID- 2225449 TI - Metastatic carcinoma of the prostate with hypercalcemia. AB - A patient presented with advanced cancer of the prostate and underwent bilateral orchiectomy. After 2 years, hypercalcemia developed and was managed successfully with saline diuresis, furosemide, and oral glucocorticoid therapy. It is believed that the patient's hypercalcemia was caused by a metabolic complication of progressive, advanced disease. PMID- 2225450 TI - Parenteral nitrogen mustard for inflammatory arthritis. AB - A patient with progressive psoriatic arthritis refractory to methotrexate therapy was treated empirically with intravenous nitrogen mustard, or HN2. His response to therapy was compared with the responses of five rheumatoid arthritis patients treated with the same regimen. At 14 days after therapy was begun the patient with psoriatic arthritis showed significant improvement, at least comparable to that observed in the rheumatoid arthritis group. Intravenous HN2 therapy may be an alternative to methotrexate for progressive psoriatic arthritis. PMID- 2225451 TI - The effects of steroid therapy on pulmonary hypertension secondary to fibrosing mediastinitis. AB - Mediastinal fibrosis, a rare cause of pulmonary hypertension, may produce cough, dyspnea, and hemoptysis. Steroid therapy has been suggested for individuals with progressive symptoms, but data demonstrating the efficacy of such therapy are lacking. We present a case of pulmonary hypertension secondary to fibrosing mediastinitis. Hemodynamic and scintigraphic studies performed before and after a trial of corticosteroid therapy were unable to demonstrate any therapeutic benefit from the corticosteroids. In order to achieve better use of steroids for the treatment of this disease, we suggest that similar determinations be made on other patients with mediastinal fibrosis who receive such treatment. PMID- 2225452 TI - The electrocardiogram in remote myocardial infarction: reassessment of criteria. PMID- 2225453 TI - NACB 13th annual symposium: diagnostic applications of nucleic acid probes in the clinical laboratory. Toronto, Canada, June 2-3, 1989. Proceedings. PMID- 2225454 TI - Current concepts in quantitative molecular hybridization. AB - Knowledge of the molecular biology of cancer and other diseases has grown enormously in the past decade. The role certain genes play in disease states is clearer, creating new opportunities for diagnostic applications of molecular biological techniques in clinical medicine. The measurement of an abundance of certain nucleic acids could be valuable as a diagnostic or prognostic test. For example, aberrant expression of growth-promoting genes has correlated with the type and severity of certain neoplasias. Also, the determination of an abundance of exogenous sequences, arising from viruses or other pathogens, can be useful for evaluating virus load and activity during infection. Changes in the levels of these sequences could provide a means to determine the efficacy of therapy. Nucleic acid sequences can be measured by molecular hybridization using complementary nucleic acids as probes. Strategies for performing quantitative molecular hybridization, and their application in the clinic, are discussed. PMID- 2225455 TI - Nucleic acid hybridization in viral diagnosis. AB - Since 1982, numerous studies have been published utilizing a variety of hybridization techniques to detect viral nucleic acid directly in clinical specimens and in tissue sections. However, hybridization techniques are still not widely used in the clinical laboratory. Other recent advances, such as the development of monoclonal antibodies for virus identification and ELISA kits for virus detection, and the introduction of centrifugation cultures for rapid diagnosis, have postponed the clinical application of hybridization techniques. Furthermore, the use of hybridization for diagnosis has been limited by its insensitivity when compared to cell culture, the need for radioisotopes to increase sensitivity, and the difficulties inherent in transferring a basic research tool to the clinical laboratory. Nevertheless, with recently developed amplification techniques and further advances in nonradioactive labelling of probes, it can be expected that nucleic acid hybridization will be an established technique in diagnostic laboratories in the near future. PMID- 2225456 TI - Aspartate aminotransferase isoenzymes. AB - Aspartate aminotransferase (AST, EC 2.6.1.1) exists in human tissues as two distinct isoenzymes, one located in the cytoplasm (c-AST), and the other in mitochondria (m-AST). Striated muscle, myocardium, and liver tissues are the main sources of AST. A growing body of information suggests that determination of AST isoenzymes in human serum is useful in evaluating damage to some of these organs. In hepatic disease, the test is used to assess liver necrosis and for determining prognosis. It may also assist in identifying patients with active alcoholic liver disease. In patients with acute myocardial infarction, measurement of AST isoenzymes provides diagnostic information that differs from that obtained by determination of total creatine kinase and lactate dehydrogenase enzymes, and their isoenzymes. PMID- 2225457 TI - Comparison of tartrate resistant acid phosphatase in a giant cell bone tumor and a spleen infiltrated with hairy cells. AB - Acid phosphatase (E.C.3.1.3.2) in a giant cell bone tumor and a spleen infiltrated with hairy cells was extracted by citrate buffer and then by 0.3 mol/L NaCl. The cationic acid phosphatase in the crude extract was isolated by CM cellulose chromatography, and further separated by high pressure liquid chromatography. The majority of the tartrate resistant acid phosphatase in the hairy cell spleen was unabsorbed on CM-cellulose and was insensitive to iron. A much larger portion of the acid phosphatase in the bone tumor, than in the spleen, was cationic and was eluted from the column by 0.8 mol/L NaCl. The cationic acid phosphatase was further separated into consecutive peaks of acid phosphatases with different sensitivity to iron. A major portion of acid phosphatase in the giant cell bone tumor was enhanced by iron, while the amounts of iron-enhanced and iron-insensitive acid phosphatase were about the same in the spleen. The differences of the phosphatases in these two types of pathologic specimens indicate the occurrence of two types of enzymes with different biological significance. PMID- 2225458 TI - A time-resolved fluoroimmunoassay for the determination of prostaglandin F2 alpha. AB - We describe a solid-phase immunoassay based on fluorescence detection for Prostaglandin F2 alpha (PGF2 alpha). Europium was used as the fluorescence marker. Prostaglandin F2 alpha was covalently bound to poly-L-lysine (PL) and labelled by coupling Eu3+ via the complexonate diethylenetriaminepentaacetic acid (DTPA). The labelled PGF2 alpha was tested in a competitive immunoassay. The detection limit for PGF2 alpha was about 2.2 pg per microtiter well. The intraassay-variation was 17.2% at 1.1 pg, 4.1% at 10 pg and 7.6% at 90 pg. The precision was determined by measuring various amounts of unlabelled PGF2 alpha (2.5 to 2,400 pg) in the assay buffer. The regression line for these studies resulted in a good correlation (y = 1.01x +/- 0.03; r = 0.996; n = 21). The results of a radioimmunoassay and of the fluoroimmunoassay were similar (y = 0.983 +/- 0.04; r = 0.988; n = 15). The new method enables PGF2 alpha analyses at concentrations in the fmolar range. PMID- 2225459 TI - Immunochemical detection of human blood in feces. AB - We have developed a new immunochemical test for fecal occult blood utilizing enzyme-linked immunosorbent assay (ELISA) of human hemoglobin (HbAo) and transferrin (Tf) simultaneously. The ELISA had a sensitivity of about 15 ng/ml Hb, and the measurable range was 1.5-750 micrograms Hb per g feces. The stability of Tf in feces was greater than that of Hb. In 17 out of 18 patients with colon cancer, 8 out of 15 patients with colon polyps, and 11 out of 20 patients with upper-gastrointestinal disorders. The Hb and Tf values were more than 10 micrograms/g feces, in terms of Hb concentration. The ELISA for human fecal HbAo and Tf might be useful for the diagnosis of gastrointestinal disorders. PMID- 2225460 TI - Apolipoprotein B-48 analysis by high-performance liquid chromatography in VLDL: a sensitive and rapid method. AB - Apolipoprotein (apo) B subspecies were separated by high-performance liquid chromatography (HPLC) to analyze Apo B-48 contents in very-low-density lipoproteins (VLDL) more easily. Apo B-100 and B-48 were eluted through two connected column of Shim-pack Diol-300 at a retention time of 24 min and 32.3 min, respectively. The molecular masses estimated by this method were approximately 600 kDa in apo B-100, 220 kDa in apo B-48. % apo B-48 in total apo B (% B-48) determined by measuring peak area of HPLC-separated apo B in a healthy subject was 76% in chylomicrons, 13% in fasting VLDL, and 20% in 2 h-postprandial VLDL. No peak of apo B-48 was detected in LDL. Recovery of Apo B determined by re chromatography of HPLC-separated sample was 91 +/- 4.0% and 95 +/- 3.6% in Apo B 100 and apo B-48, respectively. 125I-labeled apo B in VLDL were also analyzed by both HPLC and SDS-PAGE. Percent radioactivity of apo B-48 fraction in the total apo B determined by the HPLC (17.3%) was similar to the value obtained through the measurement of radioactivity separated by the SDS-PAGE (17.6%). Coefficient of variation in % B-48 determined by the peak area was 2.5%. Percent B-48 determined by the HPLC method was significantly correlated with % B-48 by SDS PAGE, but 6-8 times higher, which might be accounted for in part by the reported difference of chromogenicity between apo B-100 and apo B-48. % B-48 in VLDL separated from fasting plasma were 17.1 +/- 5.6% in 14 healthy subjects, and positively related to VLDL triglyceride and cholesterol concentrations. Apo B isoprotein analysis by the HPLC method is reliable and easy to perform for studying apo B metabolism in triglyceride-rich lipoproteins in physiological as well as pathological conditions. PMID- 2225461 TI - Enzymatic diagnosis of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency with high performance liquid chromatography. AB - A new non-radiochemical method for determination of 3-hydroxy-3-methyl-glutaryl CoA (HMG-CoA) lyase is described. Acetyl-CoA, the product of the enzymatic reaction, is separated from the substrate by high-performance liquid chromatography and is quantified. The mean 3-hydroxy-3-methylglutaryl-CoA lyase activity in control fibroblasts was 7.8 +/- 2.1 (SD) nmol/min per mg protein, and its apparent Km value was 77.8 +/- 14.3 microM (R/S mixture) with a calculated Vmax of 12.4 +/- 2.2 nmol/min per mg protein. Using this method, we could easily differentiate a patient with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency from control subjects. PMID- 2225462 TI - Lipoamidase activity in human serum is due to biotinidase. AB - Lipoamidase, as determined by lipoyl-p-aminobenzoic acid (L-pABA) hydrolyzing activity, and biotinidase in human serum have similar pH profiles, molecular weights, thermostabilities, and are similarly inhibited by p hydroxymercuribenzoate and not inhibited by phenylmethylsulfonylfluoride. A monospecific polyclonal antibody prepared against biotinidase immunoprecipitated greater than 95% of serum L-pABA hydrolyzing activity and an identical proportion of biotinidase activity. In addition, children with profound biotinidase deficiency (less than 10% normal serum activity) have greatly reduced levels of L pABA hydrolyzing activity in serum (less than 15% of mean normal activity) and obligate heterozygotes have activities intermediate between that of normal and profoundly deficient individuals. These results indicate that most, if not all, of the L-pABA hydrolyzing activity in human serum is due to biotinidase. Moreover, since the Km of L-pABA hydrolysis by serum is high, it is unlikely that lipoic acid is recycled in the serum by biotinidase. PMID- 2225463 TI - Rapid diagnosis of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency via enzyme activity measurements in leukocytes or platelets using a simple spectrophotometric method. AB - Patients with 3-hydroxy-3-methylglutaric aciduria due to a deficiency of 3 hydroxy-3-methylglutaryl Coenzyme A lyase usually present with a life-threatening crisis of hypoglycemia, metabolic acidosis and hyperammonemia. Diagnosis of this inborn error of leucine degradation is usually based upon gas-chromatographic analysis of organic acids in a patient's urine. In this paper we describe a simple spectrophotometric method allowing the activity of HMG-CoA lyase to be measured in leukocytes or platelets within a few hours, thus contributing to a rapid, unequivocal diagnosis and subsequent treatment. The validity of the method was established by demonstrating a deficient activity of HMG-CoA lyase in two patients with 3-hydroxy-3-methylglutaric aciduria. Furthermore, using this method, heterozygote detection can be done with great reliability. PMID- 2225464 TI - Evidence of acid hydrolysis as responsible for 2-(2-furoyl)-4(5)-(2-furanyl)-1H imidazole (FFI) production. PMID- 2225465 TI - The Gibbs' Boston years: early developments in epilepsy research and electroencephalography at Harvard. Interview by James L. Stone and John R. Hughes. PMID- 2225466 TI - The Gibbs' Chicago years: from Harvard in the past to Illinois in the present. Interview by John R. Hughes and James L. Stone. PMID- 2225467 TI - Intermediate and long latency SEPs in relation to clinical disability in traumatic brain injury patients. AB - Intermediate (0-60 ms) and long latency (0-500 ms) somatosensory evoked potential (SEP) patterns were compared in terms of their relationship to degree of clinical disability in severe traumatic brain injury patients. Long latency (LL) SEP patterns correlated significantly with clinical disability as measured by the Disability Rating scale while intermediate latency (IL) SEP patterns did not. Evoked potential abnormality (EPA) scores based upon LL SEP patterns appear better able to reflect extent and severity of brain dysfunction and overall clinical condition than do IL SEP patterns for severe traumatic brain injury patients. PMID- 2225468 TI - Auditory evoked potentials in narcolepsy and sleep terrors. AB - Dysfunction of brainstem reticular activating centers has been suggested in some sleep disorders, including narcolepsy and sleep terrors. Previous studies have suggested normal brainstem auditory evoked potentials (BAEPs) in narcolepsy and enhancement of long-latency auditory event-related potentials (ERPs) in sleep deprivation and conditions of pathological somnolence. Sleep terrors have not to date been studied neurophysiologically. We recorded early latency BAEPs and long latency auditory ERPs in 8 patients with narcolepsy and 5 individuals with sleep terrors, and compared them to 10 normal controls. Narcolepsy patients and controls did not differ significantly in absolute or interpeak latency of BAEPs. Sleep terror patients had significant prolongation relative to controls of III-V and I-V interpeak latencies. The N1, N2, and P3 AEP components were prolonged in latency in narcoleptic patients as compared to controls, while sleep terror patients did not differ from controls. No significant differences in amplitude were found. These findings suggest that a disturbance of integration of brainstem centers subserving wakefulness and sleep may play a role in the disordered arousal of sleep terrors, but suggest no specific abnormality in brainstem function in narcolepsy. The AEP changes in narcolepsy may be a manifestation of pathological sleepiness. PMID- 2225469 TI - Psychiatric correlates of repetitive rhythmic blinking on a routine EEG. AB - Our findings suggest that EEG tracings dominated by repetitive rhythmic blinking (RRB) may be indicative of a functional rather than an organic brain disorder. Evaluation of organicity in psychiatric patients is the most common reason for obtaining an EEG. As a normal EEG does not totally rule out organic involvement, such findings as the presence of RRB on the record may strengthen the value of EEG in such evaluations. More research is necessary to further delineate the relation between increased blinking and functional psychiatric disorders. PMID- 2225470 TI - Brain mapping in a case of multiple personality. AB - Brain maps were recorded on a patient with a multiple personality disorder (10 alternate personalities). Maps were recorded with eyes open and eyes closed during 2 different sessions, 2 months apart. Maps from each alternate personality were compared to those of the basic personality "S", some maps were similar and some were different, especially with eyes open. Findings that were replicated in the second session showed differences from 4 personalities, especially in theta and beta 2 frequencies on the left temporal and right posterior regions. A rank ordering of the differences in the brain maps of the alternate personalities from S were similar to the rank ordering of the differences in personality characteristics, as judged by the psychiatrist dealing with this patient. Maps from S acting like some of her personalities or from a professional actress portraying the different personalities did not reveal significant differences. Some of these findings are consistent with those in the literature, and the importance of detecting artifact in the raw EEG recording is emphasized. PMID- 2225471 TI - Alpha-like rhythmical activity of the temporal lobe. AB - In addition to the classical posterior alpha rhythm and Rolandic mu rhythm, a third type of rhythmical activity in alpha- (or sub-alpha-) frequency can be recorded over the temporal lobe and especially over the midtemporal region. This rhythm usually escapes detection in the scalp EEG but is commonly seen over bone defects ("breach rhythm"). With the use of epidural electrodes, however, this rhythm becomes quite prominent and dominates the activity of the temporal lobe unless there is excessive local EEG abnormality and/or pathology. This temporal rhythm lies in the range of 6-11/sec and thus often extends into the theta frequency range. There is no proven blocking effect; this mere fact sets it apart from posterior alpha and Rolandic mu rhythm. It is essentially a rhythm of the waking state but may linger into drowsiness and even into light NREM sleep. It is also separable from the highly controversial frontotemporal "kappa rhythm" of bygone times. EEG recordings from the depth of the temporal lobe (limbic structures) do not demonstrate such a rhythm that is likely to originate from the neocortical portion. Its neurophysiological and psychophysiological significance is enigmatic. PMID- 2225472 TI - Temporal minor slow and sharp activity in psychiatric patients. AB - TMSSA was found in 51 (4.7%) of 1091 psychiatric patients, with a higher incidence found in the older group (40 years of age or over). Although TMSSA was found in various disorders, a close association with cerebrovascular dementia was suggested. It was uncommon in patients with primary degenerative dementia. No increase of TMSSA was noted in cerebrovascular disorders without dementia. TMSSA was found fairly often in patients with affective disorders, neurosis, and other functional disorders, suggesting underlying mild cerebral dysfunction in some. TMSA, a variant of TMSSA, was very similar to TMSSA except for its greater frequency in cerebrovascular disorders without dementia. PMID- 2225473 TI - Pattern-reversal visual evoked potentials recorded in children with generalized epilepsy. AB - Visual potentials evoked by pattern reversal (PRVEPs) were studied in 64 normal subjects (age range 7 to 15 years) and in 15 patients with primary generalized epilepsy (age range 8 to 13 years), 10 of whom were without anticonvulsant medication. Most of them were studied during sodium valproate (VPR) therapy and some during carbamazepine (CBZ) medication. A Quadristim set (Alvar) was used to present checkerboard patterns on a TV monitor, to amplify the EEG signals and to average and plot the evoked potentials. The potentials were elicited by binocular full-field 2/s checkerboard reversals, recorded from an electrode 4 cm above the inion, and analyzed for latency, amplitude and waveform. Our PRVEP measurements examined peak latency of positive P2 (or P100) component and trough-to-peak amplitude on N1P2 wave complex. The degree of similarity between pairs of PRVEP plots were determined by Pearson correlation coefficient r for an analysis time of 150 ms. In most of our patients, no pronounced influence of the disease itself on the parameters and waveform of the normal PRVEP pattern was demonstrated if anticonvulsant drugs were not taken. In patients who were under complete seizure control, the anticonvulsant did not change the PRVEP morphology as well. The PRVEP abnormality was most pronounced in patients who were taking anticonvulsant medication, but whose seizures were poorly controlled. This pattern distortion can be revealed by the correlation coefficient, but not by other PRVEP parameters. Therefore, this coefficient may be useful as a sensitive and objective measure both of PRVEP distortion and PRVEP improvement. Our results give further evidence that nondemyelinating disorders, but with synaptic transmission defects, can produce measurable changes in PRVEP morphology. PMID- 2225474 TI - Bone mineral density and thyroid hormone therapy. AB - The purpose of this study was to evaluate prospectively the evolution of femoral and vertebral bone mineral density (BMD) in hypothyroid subjects treated with replacement doses (mean +/- SD dose of L-thyroxine = 135 +/- 32 micrograms/day) as compared to an untreated group. Vertebral bone density was also measured in other patients who had been treated for at least 2 years with either suppressive (mean dose = 154 +/- 36 micrograms/day, n = 28) or replacement doses (mean dose = 104 +/- 52 micrograms/day, n = 21) according to the thyrotrophin response (TSH) to the thyrotrophin releasing hormone (TRH) administration. In primary hypothyroid patients, a mean decrease of 5.4% (P less than 0.01) for vertebral BMD, 7.3% (P less than 0.01) for trochanter and 7% (P less than 0.001) for femoral neck was observed after 1 year of treatment. This loss was unrelated either to age or to menopausal status (ANOVA). A clinical and hormonal state of euthyroidism was reached since the 3rd month of treatment. Fasting urinary calcium/creatinine excretion was increased significantly (P less than 0.05) at the 3rd month, and plasma osteocalcin (OC) increased significantly from the 3rd month onwards (P less than 0.05) up to the 12th month (P less than 0.025). In the cross-sectional study, vertebral BMD was not significantly different from age matched normal values in patients receiving either substitutive or suppressive doses of LT4. These results suggest that in the case of primary hypothyroidism even appropriate thyroid replacement therapy could lead during the first year of treatment to a significant reduction in vertebral and femoral BMD. However, the fact that an increased fracture rate has not been documented in long-term treated patients, and the results of our cross-sectional study, suggest that this bone mass reduction could be transient and reversible due to new bone formation at the end of the resorptive sequence. PMID- 2225475 TI - Rapid and long-lasting suppression of prolactin secretion and shrinkage of prolactinomas after injection of long-acting repeatable form of bromocriptine (Parlodel LAR). AB - Five patients with PRL-secreting macroadenoma and nine patients with PRL secreting microadenoma or idiopathic hyperprolactinaemia were treated with monthly administrations of long-acting bromocriptine suitable for repeatable injections (Parlodel LAR) for 1-12 cycles of treatment. A significant shrinkage of tumour mass and the recovery of visual field defects were observed in patients with macroprolactinoma. Plasma PRL levels decreased to 16.8 and 18.1% of pretreatment values, in macroprolactinoma and idiopathic or microadenomatous hyperprolactinaemic subjects, respectively, during the first cycle of treatment, reaching the normal range in three patients of each group. During the following cycles of treatment, two patients with macroprolactinoma and one patient with idiopathic or microadenomatous hyperprolactinaemia became normoprolactinaemic. Adverse reactions generally did not last beyond the first days of administration and decreased with the progression of the treatment. In conclusion, its effectiveness and the fact that it is well tolerated, may suggest that this form of bromocriptine may be used as a first therapeutic approach for patients with PRL-secreting adenomas, particularly when shrinkage of a macroadenoma is urgently required. PMID- 2225476 TI - Role of cholinergic muscarinic pathways on the free fatty acid inhibition of GH responses to GHRH in normal men. AB - In order to explore the mechanisms by which free fatty acids (FFA) inhibit GH secretion, we studied the effect of the acetylcholinesterase inhibitor pyridostigmine (120 mg p.o.) on the FFA blockade of GH responses to the administration of GHRH (100 micrograms i.v.) in seven normal subjects. GHRH induced GH secretion was significantly reduced following elevation of circulating FFA levels by lipid-heparin infusion and significantly potentiated by previous pyridostigmine treatment. Peak GH levels following combined administration of pyridostigmine plus lipid-heparin plus GHRH were significantly higher (P less than 0.01) than after GHRH alone and significantly lower than after pyridostigmine plus GHRH (P less than 0.01). In conclusion, central cholinergic activation by pyridostigmine, with the presumed reduction in somatostatin discharge, reversed the blocking effect of FFA on GHRH-stimulated GH release. Conversely, FFA were able to reduce even a maximal GH stimulation by pyridostigmine plus GHRH. PMID- 2225477 TI - Baroreflex-governed sympathetic outflow to muscle vasculature is increased in hypothyroidism. AB - Microelectrode recording of muscle nerve sympathetic activity (MSA), which is baroreflex-governed and involved in cardiovascular homeostasis, was made in five patients with hypothyroidism and in seven patients with hyperthyroidism prior to treatment and after recovery to euthyroidism. Patients with hypothyroidism had a higher level of MSA when hypothyroid than after recovery (mean +/- SEM 39.3 +/- 7.1 and 26.8 +/- 7.9 bursts/min, respectively, P less than 0.05), whereas hyperthyroidism was not accompanied by a change in the number of sympathetic bursts/min. The response of MSA to manouvres known to influence the neural outflow via baroreceptors and other receptor inputs was not changed with altered thyroid function. The findings provide direct evidence of an increased sympathetic activity in hypothyroidism, but suggest that other physiological properties of MSA are intact in thyroid disease. PMID- 2225478 TI - The effect of amiodarone on the control of hyperthyroidism by propylthiouracil. AB - We studied the efficacy of amiodarone (800, 600, 400 and 200 mg orally daily during weeks 1, 2, 3 and 4, respectively) plus propylthiouracil (PTU, 100 mg orally every 8 h) in comparison to PTU alone in the early treatment (28 days) of Graves' disease patients. Circulating T3 and T4 decreased earlier and more markedly in the amiodarone plus PTU-treated group. An initial rise of circulating rT3 above the base-line value followed by a gradual decline was observed in the former group while only a decline below the base-line values was observed in the latter group. The resting pulse rate decreased and body weight increased significantly in the amiodarone plus PTU-treated group. In the PTU-treated group, significant weight gain was observed later in the course of treatment while no significant reduction in pulse rate was observed. No major side-effects of amiodarone were observed during the course of treatment. This study suggested that the combination of amiodarone and PTU was more efficacious than PTU alone in reducing circulating T3, T4 and clinical hyperthyroidism early in the course of treatment of patients with Graves' disease. This regimen has an additional potential advantage because of the antiarrhythmic property of amiodarone, especially in situations when a beta-blocker is contraindicated. PMID- 2225479 TI - Overnight urinary growth hormone measurement in the diagnosis of acromegaly. AB - Several studies report higher urinary GH excretion in acromegalic patients compared to control subjects. We investigated the diagnostic potential of overnight urinary GH excretion in acromegaly, using a recently developed enzyme linked immunosorbent assay. Overnight urine samples were obtained from 117 control subjects and nine patients with untreated acromegaly. GH excretion was higher in acromegalic patients compared to control subjects, with geometric mean total overnight values of 46.35 and 5.73 microU respectively. The range for total overnight urinary GH in control subjects was 0.75-21.75 microU and two of the nine patients with untreated acromegaly had GH measurements within this range. Urinary GH measurements were corrected using predictive clinical variables but this resulted in minimal improvement in discrimination between control subjects and acromegalic patients. Lack of complete discrimination between control subjects and acromegalic patients limits the usefulness of a single overnight urinary GH measurement as a screening test for acromegaly. PMID- 2225480 TI - Thyroid function in choriocarcinoma: demonstration of a thyroid stimulating activity in serum using FRTL-5 and human thyroid cells. AB - Hyperthyroidism is a well recognized complication of gestational trophoblastic tumours (GTT) and may be due to high circulating concentrations of human chorionic gonadotrophin (hCG) or its variants. We have studied 24 clinically euthyroid women with GTT. Eight were biochemically hyperthyroid with low or undetectable serum thyrotrophin (TSH) and had a mean serum hCG of 361.2 x 10(3) IU/l compared to 76.2 x 10(3) IU/l in the other patients (P less than 0.01). Purified hCG stimulated iodide uptake into FRTL-5 cells with 25 x 10(3) IU/l being equivalent in potency to 1 mU/l of thyrotrophin (TSH). Sixteen out of the 24 sera (67%) stimulated iodide uptake when applied to the cells at a 1:10 dilution. Sera from all eight hyperthyroid patients contained thyroid stimulating activity. The mean hCG concentration in the 16 stimulatory sera was 238.2 x 10(3) IU/l compared to 37.1 x 10(3) IU/l in the other eight sera (P less than 0.01). Six men with hCG-secreting testicular tumours were biochemically euthyroid although three of their sera stimulated iodide uptake into FRTL-5 cells. In human thyroid cells the mean cAMP production over 4 h with sera from five healthy controls was 54.2 +/- 1.81 pmol/mg cell protein compared to 67.0 +/- 3.8 pmol/mg protein with sera from five choriocarcinoma patients (P less than 0.02). Serum from patients with gestational trophoblastic tumours contains a thyroid stimulating activity which may be hCG and whose presence correlates with hyperthyroidism. PMID- 2225481 TI - Subcutaneous growth hormone-releasing hormone augments pulsatile nocturnal GH release in GH-insufficient children, but may also raise basal GH secretion. AB - Growth hormone-releasing hormone (GHRH) when given s.c. to GH-insufficient children either as pulses, or once or twice daily, promotes linear growth. These treatment regimens, however, are not ideal as they require frequent drug administration and a significant proportion of patients do not show improved growth. We have now investigated the GH response to a nocturnal s.c. infusion of GHRH (1-29)NH2, at two dosages, 5 and 10 micrograms/kg/h, in a group of five GH insufficient children. The s.c. infusion of GHRH between 2100 h and 0600 h augmented nocturnal pulsatile GH release in all five children. There was a dose dependent response for the GH area under the curve (AUC), and mean total GH concentration. The AUC for GH was significantly greater after the 10 than 5 micrograms/kg/h GHRH which in turn was greater than that after placebo; mean (SD) AUC: 14816 (3978), 8125 (1931), 3032 (1582) mU min/l respectively (P less than 0.01 and P less than 0.05). There was no significant change in the number of GH pulses during the 9-h infusions when the subjects were infused with GHRH 10 or 5 micrograms/kg/h compared to placebo, and they occurred at similar times although the number of pulses tended to be greater after GHRH; the mean (SD) numbers of GH pulses were 5.0 (0.7), 3.8 (0.8), 3.2 (0.8), respectively. There was however a significant rise in the mean baseline GH concentration in all patients during the infusion of GHRH 10 micrograms/kg/h compared to placebo, but not with 5 micrograms/kg/h. Thus, GHRH(1-29)NH2 given s.c. augmented nocturnal pulsatile GH release in GH-insufficient children but it also increased baseline GH secretion. These results suggest that a sustained release preparation of GHRH could be a potential treatment for GH-insufficient children, and that a dose of 5 micrograms/kg/h would promote pulsatile GH release, but that at higher dosage it may also raise basal GH secretion. PMID- 2225482 TI - The epidemiology of thyrotoxicosis in New Zealand: incidence and geographical distribution in north Canterbury, 1983-1985. AB - In a 3-year (1983-1985) epidemiological study of thyrotoxicosis in North Canterbury, New Zealand, the annual incidence was 25.8 per 100,000 (female 40.7, male 10.5). Thyroid scintiscanning showed that 64% had diffuse hyperplasia (DH), 27% toxic multinodular goitre (TMG), 7% toxic uninodular goitre (TUG), and 2% zero uptake. The calculated annual incidence of toxic diffuse goitre (DH) was 15 per 100,000, and for toxic nodular goitre (TMG and TUG combined) was 8 per 100,000. The age-related incidence for toxic diffuse goitre peaked in middle life whereas toxic nodular goitre showed an increasing incidence with age. There was no significant seasonal variation or rural/urban difference in incidence. Analysis of geocoded addresses did not identify areas of high incidence. The variable duration of symptoms prior to diagnosis limits the search for possible environmental trigger factors. North Canterbury was an endemic goitre area prior to the introduction of iodized salt 50 years ago, and the incidence of toxic nodular goitre is likely to fall in future. PMID- 2225483 TI - Diurnal salivary cortisol patterns during pregnancy and after delivery: relationship to plasma corticotrophin-releasing-hormone. AB - The circadian rhythm of salivary cortisol was studied in 10 healthy women every 4 weeks throughout pregnancy. In addition, in 12 women the diurnal patterns of salivary cortisol, serum cortisol, plasma ACTH, plasma CRH and serum progesterone were analysed in late third trimester pregnancy and again 3-5 days after delivery. Salivary cortisol profiles exhibited a clear circadian rhythm during pregnancy with an increase in mean salivary cortisol from the 25th to 28th week onwards reaching concentrations in late pregnancy more than twice as high as in non-pregnant controls, rapidly returning to normal concentrations after delivery. The coefficient of variation of salivary cortisol profiles decreased in third trimester pregnancy due to a parallel upward shift of cortisol concentrations (40.2 +/- 3.4% vs 77.6 +/- 6.6% after delivery, P less than 0.01). A diurnal pattern was also found for plasma ACTH and serum cortisol before and after delivery with lower concentrations post-partum (P less than 0.01). In late pregnancy, progesterone concentrations were significantly higher in the evening (930 +/- 85 nmol/l vs 813 +/- 74 nmol/l at 0900 h, P less than 0.01) but showed no diurnal variation post-partum. Plasma CRH was significantly elevated in late third trimester pregnancy (1.22 +/- 0.23 micrograms/l at 0900 h) but showed no diurnal change (1.30 +/- 0.28 micrograms/l at 1900 h). Moreover, no correlation between the free cortisol increase in late pregnancy and plasma CRH was noted despite a wide range of CRH levels (0.13-3.60 micrograms/l). In contrast, a significant correlation was observed between the serum progesterone increase and the salivary cortisol increase in late pregnancy (r = 0.70, P less than 0.05). These findings demonstrate that placental CRH is not the only regulator of maternal ACTH and cortisol release. Instead, our study suggests that placental CRH has little influence on baseline maternal adrenocortical function in pregnancy. The elevated salivary cortisol levels in pregnancy may be explained by glucocorticoid resistance owing to the antiglucocorticoid action of high progesterone concentrations. PMID- 2225484 TI - Effect of enhancement of endogenous cholinergic tone with pyridostigmine on growth hormone (GH) responses to GH-releasing hormone in patients with Cushing's syndrome. AB - Growth hormone (GH) secretion in patients with Cushing's syndrome is diminished to all the stimuli tested so far but the precise mechanisms through which this occurs are unknown. In order to investigate whether increased somatostatinergic tone might be responsible for this alteration, we studied the effect of pyridostigmine (120 mg p.o. at -60 min), which activates cholinergic synapses and thus suppresses hypothalamic somatostatin release on GH responses to GHRH (100 micrograms, i.v. at 0 min), in six patients with Cushing's syndrome. We found that while pyridostigmine markedly potentiated GH responses to GHRH, in all the normal subjects tested (n = 12), neither GHRH alone nor GHRH plus pyridostigmine elicited any increase in GH secretion in any of the patients with Cushing's syndrome. This suggests that chronic glucocorticoid excess induces marked alterations in the hypothalamic control of GH secretion. PMID- 2225485 TI - The influence of octreotide treatment on pulsatile growth hormone release in acromegaly. AB - The pulsatile release of GH was investigated in eight active acromegalic patients before and during a subcutaneous infusion of 300 micrograms octreotide/24 h for 4 weeks. The number of GH pulses increased from a basal value of 14.4/24h to 16.3/24h during octreotide therapy. At the same time the mean GH concentration, valley concentration, peak height and amplitude decreased significantly. The inhibitory effect of octreotide on pulse characteristics did not depend on the time of day. IGF-I levels also decreased significantly; in five patients normal levels were reached. IGF-I levels correlated significantly with the mean GH level (r = 0.714, P less than 0.001), mean valley concentration (r = 0.697, P less than 0.001) and, to a lesser extent, area under the curve (r = 0.436, P = 0.033), but not the number of pulses. Plasma octreotide levels did not correlate with pulse parameters. In all but one patient a circadian rhythm was present during both the basal study and octreotide therapy. Compared with surgically treated acromegalics, the number of GH pulses was higher in untreated and octreotide treated patients. This study demonstrates the pulsatile release of GH in active acromegaly both before and during octreotide therapy. This result suggests that endogenous GHRH is important for the generation of GH pulses in this disease. PMID- 2225486 TI - A role for epidermal growth factor in the follicular paracrine system? PMID- 2225487 TI - Familial benign hypercalcaemia: hypercalciuria and hypocalciuria in affected members of a small kindred. AB - Familial benign hypercalcaemia has also been termed familial hypocalciuric hypercalcaemia because a major feature of this condition has been a relative hypocalciuria in relation to the hypercalcaemia, such that the calcium to creatinine clearance ratio is less than 0.016. The following is a report of a small kindred of patients with familial benign hypercalcaemia in which two of the affected members have frank hypercalciuria. PMID- 2225488 TI - Factors influencing urinary 6-sulphatoxymelatonin, a major melatonin metabolite, in normal human subjects. AB - 6-Sulphatoxymelatonin (aMT6s) has been measured, by a direct radioimmunoassay, in urine from 130 normal volunteers aged 2-80 years. Its relationship to a number of physiological parameters has been assessed. Total urinary excretion of aMT6s did not vary in a group of 40 children aged 2-20 years (24 boys and 16 girls) except when expressed as a function of body weight. In this case, total aMT6s excretion over 24 h decreased as a function of age. In 90 adult volunteers (44 men and 46 women) aged 20-80 years, there was an age-related decline in total 24 h aMT6s excretion with significantly lower values in elderly subjects. In this same adult group no relationships were found between total aMT6s excretion and body weight or height. No sex differences were found either in the 2-20 years or the 20-80 years groups. Pineal calcification was assessed by lateral skull X-ray in 26 adult volunteers (17 men and 9 women) aged 20-50 years. No significant differences in aMT6s excretion were found as a function of pineal calcification. In 16 of these subjects plasma melatonin and aMT6s also showed no relationship to pineal calcification. These studies confirm the usefulness of aMT6s as an index of melatonin secretion in normal volunteers. PMID- 2225489 TI - Long-term follow-up of low-dose external pituitary irradiation for Cushing's disease. AB - Twenty-four patients (three male) with Cushing's disease, aged between 11 and 67 years, were treated with low-dose external pituitary irradiation (20 Gy in eight fractions over 10-12 days) and followed for between 13 and 171 months (median 93 months). Eleven patients (46%) went into remission 4-36 months after irradiation, but five subsequently relapsed. Two of these received no further active treatment, one underwent successful pituitary surgery, one underwent a second course of low-dose external irradiation (as yet unsuccessful) and one has been treated with metyrapone for a total of 75 months. One of the 13 patients who did not respond received a further course of low-dose pituitary irradiation with prompt remission and two have received metyrapone for 41 months and 15 years without ill effect. One patient died from cerebrovascular disease. The remaining nine patients underwent bilateral adrenalectomy (one after unsuccessful pituitary surgery) with rapid resolution of hypercortisolism. Five of these patients have developed hyperpigmentation and elevated ACTH levels (range 505-1150 ng/l). A pituitary microadenoma has been demonstrated on CT scan in three and successfully removed by microadenomectomy. In the present series, the low incidence of radiation-induced hypopituitarism and absence of other complications attributable to radiotherapy suggest that low-dose pituitary irradiation may be a useful treatment option in selected patients. However, long-term follow-up has demonstrated a high relapse rate and failure to prevent Nelson's syndrome in adrenalectomized patients, indicating that it should not be used as primary treatment in preference to selective adenomectomy. PMID- 2225490 TI - Insulin secretion, insulin sensitivity and glucose-mediated glucose disposal in thyrotoxicosis: a minimal model analysis. AB - In order to evaluate simultaneously in thyrotoxic subjects the relative contributions of insulin secretion, insulin-sensitivity (SI) and glucose-mediated (SG) glucose disposal to overall glucose tolerance, seven non-obese patients with thyrotoxicosis were studied by the minimal model analysis of the frequently sampled intravenous glucose tolerance test, before and greater than 1 month after being rendered euthyroid, and compared with eight healthy control subjects. Basal glucose, C-peptide and glucagon levels were similar in all groups but, in the toxic and euthyroid states, basal insulin levels were significantly elevated compared to the control group (11.2 +/- 2.0 and 7.9 +/- 1.1 vs 5.1 +/- 0.6 microU/ml, mean +/- SE, P less than 0.02). FFA levels were raised in the thyrotoxic subjects prior to treatment (0.95 +/- 0.11 vs 0.68 +/- 0.08 and 0.54 +/- 0.08 mmol/l, P less than 0.02). Glucose tolerance (Kg) was reduced in the thyrotoxic subjects compared to the euthyroid state (1.16 +/- 0.12 vs 1.44 +/- 0.13 per min, P less than 0.025) and control group (1.44 +/- 1.0 per min, 0.05 less than P less than 0.1). First phase (phi 1) and second phase (phi 2) insulin release were both significantly elevated in the thyrotoxic and euthyroid states compared to the control group (phi 1 7.10 +/- 1.88 and 5.29 +/- 1.03 vs 1.72 +/- 0.17 microU/mg/min X 10(-2), P less than 0.01; phi 2 18.64 +/- 3.14 and 16.74 +/- 4.48 vs 9.23 +/- 0.74 microU/mg/min X 10(-2) respectively, P less than 0.02). SG was similar in all groups but SI was significantly reduced in the thyrotoxic subjects compared to the control group (2.24 +/- 0.62 vs 5.92 +/- 1.50/min/microU/ml X 10(4), P less than 0.02) and rose post-treatment in the euthyroid subjects (4.23 +/- 1.75/min/microU/ml X 10(4)). In the thyrotoxic subjects before and after treatment, log SI correlated negatively with basal FFA levels (r = -0.57, P less than 0.05) and with phi 2 (r = -0.58, P less than 0.05). The fractional clearance rate of insulin was unaltered by the thyrotoxic state. It is concluded that in thyrotoxicosis the impairment of Kg is due to reduced insulin sensitivity in the presence of enhanced insulin secretion, but glucose-mediated glucose disposal is unaltered by the toxic state. PMID- 2225491 TI - The influence of growth hormone on sleep in adults with growth hormone deficiency. AB - Eight patients with isolated growth hormone deficiency (IGHD), 20-30 years old were studied with polysomnography before and after 6 months of treatment with growth hormone (GH). During GH treatment total sleep time decreased and REM sleep time increased significantly. Delta sleep time (stage 3 + 4) did not change significantly. All patients reported improved well-being and none wished to discontinue the treatment with growth hormone. These findings suggest that GH has an effect on sleep. The effect of increased REM sleep in humans is incompletely understood, but sleep recordings may be one way of directly monitoring the effect of GH on the central nervous system. PMID- 2225492 TI - The prevalence of polycystic ovaries in patients with congenital adrenal hyperplasia and their close relatives. AB - Seventy-seven female patients (36 adults and 41 children aged under 16 years) with congenital adrenal hyperplasia (CAH) were assessed using pelvic ultrasound, as well as with standard endocrine tests and HLA typing. Forty-six close female relatives were also tested for ovarian morphology using ultrasound after assessment of their heterozygous state using HLA typing. The association of CAH with ultrasonically detected polycystic ovaries (PCO) was confirmed in 30/36 (83%) adult patients, 4/10 (40%) postpubertal girls and 1/31 (3%) pre and peripubertal girls: in all, 35/46 (76%) postmenarcheal patients. Six out of nine (67%) pre-menopausal mothers of patients with PCO, and 8/10 (80%) sisters of patients with PCO also had PCO. The proportions of both CAH patients and heterozygote subjects with PCO were significantly greater than that found in a normal population (P less than 0.0001). The finding, however, of two homozygous non-CAH-affected adult sisters with PCO and, conversely, of 10 heterozygous adult relatives and of 12 postmenarcheal CAH patients with normal ovaries, indicates that the ovarian morphological change may be independent of the adrenal lesion. PMID- 2225493 TI - The management of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. PMID- 2225495 TI - Informed consent in head and neck surgery. AB - Informed consent is the fastest growing problem in the medical negligence debate. It was highlighted recently in the United Kingdom in the Sidaway case. Informed consent comprises the advice you would give the patient, the consequences of not taking your advice, the specific risks of the surgery or treatment you have in mind, and the risks of surgery in general. In an attempt to identify what the present practice in otolaryngology was, a postal survey was carried out of the members of the Scottish and North of England Otolaryngological Societies. PMID- 2225494 TI - Neurodegeneration and the nose. PMID- 2225496 TI - Repair of salivary fistulae after laryngectomy. AB - A new surgical technique is described for the repair of salivary fistulae. It has been used in three patients. The fistulae occurred after laryngectomy and had been unsuccessfully treated with local and regional flaps. The principle of the technique is to use a bipedicled jejunal patch as a free microvascular transfer. One patch is used for reconstruction of the pharynx and after excising the mucosa the skin defect is closed with the other patch. The mucosa is excised to expose the muscle and to create a recipient site for a split skin graft. PMID- 2225497 TI - The influence of calcium alginate haemostatic swabs upon operative blood loss in adenotonsillectomy. AB - Although adenotonsillectomy is regarded as a minor procedure, it has been shown that 18% of patients may experience an operative blood loss of 10-20% of the total blood volume. The aim of this study was to determine whether calcium alginate haemostatic swabs reduce operative blood loss in adenotonsillectomy. Seventy-two patients (ages 2-12 years) entered a prospective trial in which the operation was performed either with normal gauze swabs or calcium alginate swabs. Thirty-six children were randomized to each group. The mean blood loss was found to be 34.9 ml (2.07% of total blood volume) and 47.8 ml (2.97% of total blood volume) respectively. Although there was no significant reduction in operative blood loss using calcium alginate, in both groups the blood loss was much smaller than that stated by the majority of previous workers. PMID- 2225498 TI - Obstructive sleep apnoea in children undergoing routine tonsillectomy and adenoidectomy. AB - Sleep screening was used to discover the incidence of sleep apnoea in 50 children undergoing routine adenotonsillectomy for recurrent upper respiratory tract infections, randomly selected from the waiting list. Preoperative assessment included a detailed parental history, physical examination, and lateral cephalometry, in order to identify factors that might alert the clinician to a diagnosis of obstructive sleep apnoea. There were 2 equal groups of snorers and non-snorers (grade 0); 1 patient was found to have the sleep apnoea syndrome (IV), 9 patients had obstructive snoring with apnoeic episodes (III), 3 patients had snoring with a disrupted sleep pattern (II), and 12 patients snored with no disruption of sleep (I). In identifying patients with apnoea, a history of snoring was unhelpful, whereas one of breathing irregularities was found to be highly specific. Nasal obstruction correlated poorly; however, there was a significant relationship between tonsillar position and size and sleep grade (Chi squared P less than 0.01). Stepwise regression analysis showed a large contribution to the grading was made by the size of the oropharyngeal airway measured by lateral cephalometry. The children in grade II-IV were re-studied 3 months post-operatively and all reverted to grades 0 or I. PMID- 2225499 TI - Ear drops and grommets. AB - The relative ease with which different ear drops pass through grommets of different designs has been investigated using a laboratory model. The viscosities of the various ear drop preparations tested have also been determined. There is a considerable variation in the volume of ear drops required to penetrate ventilation tubes. Their ease of passage is determined by the size of the tube and is probably also related to the ease with which a preparation wets the surface of the grommet. There is no relationship between ease of penetration and viscosity. The penetration of ear drops through grommets during episodes of aural discharge was studied in vivo. Penetration into the middle ear was observed only when the drops were introduced using the displacement technique. It was more readily achieved when the grommet lumen was free of discharge. PMID- 2225500 TI - Hearing aids for high-frequency hearing loss. AB - This cross-over study compares the relative benefits of a standard NHS contracted hearing aid with a high-frequency emphasis commercial aid in subjects with high frequency hearing loss. Disability questionnaires and free-field speech-in-noise (FAAF II) tests were used to assess subjects unaided and after 6 weeks of wearing each aid. Total FAAF II test scores showed no significant difference with either aid, but analysis of frequency-specific subscores demonstrated less use of low frequency information when using the high-frequency emphasis aid. Overall questionnaire responses relating to conversation showed more benefit with the high-frequency emphasis aid. Subjects generally preferred this aid, possibly due to less low-tone gain than the standard NHS aid. PMID- 2225501 TI - Peak flow nasal patency indices and self-assessment in septoplasty. AB - The present study evaluates the results of septoplasty monitored by the objective peak flow nasal patency indices and the subjective patient self-assessment scores of nasal obstruction. Mini-Wright peak flow meters were used. The peak flow nasal patency index was defined as the ratio between nasal and oral peak flow rates. Uni and bi-lateral, as well as ex and in-spiratory, indices were calculated. Both peak ex and in-spiratory flow nasal patency indices were significantly increased 1 and 6 months post-operatively, indicating improved nasal patency. The most marked post-operative increase of the nasal patency indices was seen for the preoperatively worst airway and the total airway. A weak significant positive correlation was found between the peak flow nasal patency indices and the patient mean self-assessment scores of the uni and bi-lateral nasal obstruction. The change of the peak flow nasal patency indices measured 6 months post-operatively correlated well with the patient overall assessment of the operative changes of the total nasal patency. The method was found quick and easy to handle in monitoring the effect of functional septoplasty and is recommended as an alternative to rhinomanometry. PMID- 2225502 TI - Advice to candidates sitting the Final Fellowship Examination. AB - This paper is intended to provide guidance to candidates sitting the Final Fellowship Examination in Otolaryngology of the Royal College of Surgeons of Edinburgh. Although some of the advice given is specific to the Fellowship in Otolaryngology of that College, much of it is of relevance to any examination. PMID- 2225503 TI - Analgesia and removal of nasal packing. AB - We present a prospective controlled trial, comparing methods of analgesia for the relief of discomfort on removing nasal packing, including a general discussion on the considerations for, and methods of, nasal tamponade. On the basis that nasal packing is likely to continue to be used frequently, nitrous oxide (as Entonox) is advocated as a safe and relatively cheap means of pain relief with a statistically significant advantage over papaveretum. PMID- 2225504 TI - A randomized comparison of manipulation of the fractured nose under local and general anaesthesia. AB - Reduction of simple nasal fractures may be performed under local or general anaesthesia: the latter is by far the most popular method in Britain, though why is hard to define. We have attempted to compare the 2 approaches by means of a randomized, prospective trial. Fifty consecutive, adult patients with radiologically proved fractures of the nasal bones were randomized to a local or general anaesthesia group and underwent manipulation with Asch's and Walsham's forceps between 7 and 15 days post-injury. Analysis of results at 4 h and 8 weeks post-operatively showed no significant benefit conferred by fracture reduction under general anaesthesia as opposed to local anaesthesia with respect to post operative airway patency or cosmesis. It is suggested that significant benefits can be obtained in terms of patient convenience and cost effectiveness if nasal fractures are reduced under local anaesthesia as an outpatient procedure. PMID- 2225505 TI - Trimming of the inferior turbinates: a prospective long-term study. AB - The aim of this study was to determine whether the initial benefits of radical trimming and anterior trimming of the inferior turbinates on nasal airflow persisted in the long term. Radical trimming significantly reduced nasal resistance at 2 months following operation (n = 12) (P less than 0.005). There was no significant change in nasal resistance over the next 20 months. Symptom scores for nasal obstruction also showed a significant reduction (n = 16) (P less than 0.005), at 2 months, and did not change significantly over the next 20 months. Radical trimming of the inferior turbinates is a highly effective operation in patients with hypertrophy of the inferior turbinates with few initial complications. However, further analysis of the data revealed that up to 20% of patients lose the initial subjective benefit of relief of nasal obstruction within 2 years of follow-up. Late onset crusting occurs in some patients though this is not directly attributable to an increase in nasal airflow. This study also concludes that anterior trimming of the inferior turbinates cannot be recommended as a form of treatment. PMID- 2225506 TI - Sensorineural hearing loss in bullous myringitis. A prospective study of eighteen patients. AB - Eighteen patients were seen over a period of 3 years. Twenty of their ears were diagnosed as having bullous myringitis. Pure tone audiograms and stapedial reflexes were performed within 48 h of referral. Six ears demonstrated sensorineural hearing loss, 7 ears mixed loss and 4 conductive loss. Recovery of sensorineural hearing loss complete in 8 out of 13 ears. Stapedial reflexes were elicited in 5 patients and all showed recruitment. The findings of this study confirms the fact that sensorineural hearing loss is more common in bullous myringitis than previously thought and that it is temporary in many cases. The stapedial reflex results suggest that the site of the lesion is in the cochlea. PMID- 2225507 TI - Vitreous carbon: a new material for middle ear ventilation tubes. AB - Synthetic allotropic carbons have been used for nearly 20 years as biomedical implants. Vitreous carbons in particular appear to possess very favourable biocompatibility characteristics. The middle ear compatibility of Sigradur has been tested in the mastoid bulla of gerbils. The period of implantation varied from 1 to 13 months. Light and electron-microscopic examination revealed good middle ear tolerance of the material, especially when the surface had not been modelled. Our animal experiments suggest that this material could be suitable for ventilation tubes, but was less ideal for ossicular replacement prostheses, particularly because of the specific surface properties. Consequently, we have used such carbon ventilation tubes in 38 patients. The results obtained using this material were excellent thanks to the favourable biocompatibility, advantageous surface properties, and low weight. PMID- 2225509 TI - The Netherlands ENT Society. 168th meeting. Maastricht, 4-5 November 1988. Proceedings. PMID- 2225508 TI - Chest infection following head and neck surgery: a pilot study. AB - This paper reports the results of a pilot study which examined factors associated with chest infection following head and neck surgery. The overall rate of chest infection was 11%, but was 20% in those patients having a tracheotomy. No infection developed in patients with an intact airway. Other factors which emerged as possibly important were the duration of surgery and heavy regular alcohol intake. We recommend that prophylactic antibiotics be continued for at least 48 h in patients requiring a tracheotomy as part of their head and neck surgery. This is against the trend of shorter antibiotic regimens recommended for prevention of wound infections. PMID- 2225510 TI - A model for instruction in myringotomy and grommet insertion. PMID- 2225511 TI - Wegener's granulomatosis: otorhinolaryngological manifestations. PMID- 2225512 TI - Long-term intragastric pH measurement in man. Selected papers from an international workshop. London, September 14, 1987. Proceedings. PMID- 2225513 TI - Royal Free Hospital protocol for 24-hour intragastric acidity and plasma gastrin concentration. AB - The Royal Free Hospital protocol for simultaneous measurement of 24-hour intragastric acidity and plasma gastrin concentration is described in detail. The methods of analysing such data are discussed, with recommendations for a standard four-way analysis: median hourly 24-hour intragastric acidity or pH, or plasma gastrin concentration; integrated 24-hour intragastric acidity, or plasma gastrin concentration; analysis of integrated values according to meal-related intervals; and quantification of the percentage of time in a 24-hour period that intragastric pH is greater than 3. PMID- 2225514 TI - Electrochemical aspects of pH electrodes. AB - When a pH electrode is applied intragastrically for long-term pH metry, problems may occur which are related to the specific conditions of gastric juice and to the possible difference between the temperature of buffer solutions and the body temperature. The fact that pH electrodes measure the activity of the hydrogen ion instead of its concentration may, in concentrated solutions (i.e. pH less than 2), lead to an error that is even compounded if other ions are present in high concentrations. This error normally does not influence comparisons between measurements obtained under the same conditions. It is, however, important to check which correction procedures are provided for the particular devices being used when comparing results obtained by different research groups. Calibration of the electrode at a temperature differing from body temperature may result in an important error. Complete correction for this error may be achieved for glass electrodes by a modified version of the Nernst equation; for monocrystalline antimony electrodes an empirically derived formula is available allowing for partial correction. In general, all types of electrodes should be calibrated using two different buffer solutions (one with a pH value between 6 and 8 and another with a pH of 2 or less) and the double-point interpolation method. PMID- 2225515 TI - Comparison of gastric aspiration and continuous pH monitoring with antimony electrode: methodological remarks. AB - In an attempt to eliminate the noise affecting continuous 24-hour intragastric pH metry curves in order to obtain a more appropriate identification of hourly intraluminal pH values to which the corresponding aspirate ones were compared, the raw data of one of our previous experiments were treated using a smoothing technique (removal of noise peaks was followed by moving averages on three adjacent points, 1 min apart, which were applied both singly and combined with Fourier's filtration employing the first 32 harmonics) A gradual improvement of all parameters of regression analysis from original data to those achieved with the two above-mentioned methods was found. In particular, the regression coefficient r increased from 0.83 to 0.88 with the singly moving averages technique and even to 0.95 when Fourier's filtration was combined. Both techniques provided also similar improvement as far as slope and elevation values were concerned: the slope was almost equal to 1 and the elevation was very low, so that paired data might be assumed to be proportional. It can be concluded that hourly pH values of continuous intraluminal monitoring and those of simultaneous gastric aspiration appear better correlated if the elimination of noise disturbing the in vivo pH metry curves is obtained. With regard to this, the use of a combined smoothing-filtering technique, such as moving averages plus Fourier's filtration after removal of the noise peaks, seems a very advantageous modality. PMID- 2225516 TI - Gastric aspiration technique for pH recording: a critical evaluation of this method. AB - The most often used methods for the measurement of intragastric acidity are repeated mostly hourly aspirations of gastric contents or continuous pH measuring with an electrode. Intragastric pH, volume of aspirated gastric juice and total acid secretion have been tested over relatively short periods of time (2-12 h) and through an entire 24-hour period. Nearly every clinical antiulcer drug which neutralizes acidity or inhibits acid secretion has been investigated with this method. pH monitoring with the gastric aspiration procedure is a reliable and reproducible method. There is a remarkable global agreement in the results. While pH electrodes provide an alternative means of measuring pH, they have the disadvantage of not allowing measurement of volume and/or acid secretion. PMID- 2225517 TI - Do hourly averaged pH readings correlate with those from point readings of aspiration? Comparison of two different electrode positions with simultaneous aspiration. AB - Hourly averaged data from continuous intraluminal pH recording were compared with the point aspiration in five 24-hour studies performed on healthy volunteers. Two different electrode positions were compared simultaneously with aspiration. The correlation was performed using the median from the whole hour's recording of the electrode against the aspiration point. There was a significant correlation between both electrodes and aspiration (p less than 0.001), although both electrodes read consistently lower than aspiration: electrode A (gastric antrum), median pH = 1.4; electrode B (gastric body), pH = 1.9; aspiration, pH = 2.3. These findings show that data reported in clinical trials using different recording techniques are not directly comparable and must be interpreted appropriately. The position of the electrode may also be important. PMID- 2225518 TI - Simultaneous comparison of 24-hour intragastric pH recording using glass and antimony electrodes in man. AB - Based upon the results of in vitro studies, antimony electrodes are generally considered to have inferior electrochemical properties when compared with glass electrodes. Since a direct comparison in man is lacking, a 24-hour ambulatory intragastric pH recording was performed in 10 healthy male subjects simultaneously using glass and antimony electrodes. In the first set of experiments (when both electrodes were calibrated in buffers of pH 7 and 1 at 37 degrees C: beaker calibration) significantly lower pH recordings during fasting periods were registered with the antimony electrode. This difference could be corrected by a modified calibration, using the external skin reference electrode of the antimony electrode (finger calibration). In the second series of experiments (performed after finger calibration) comparable recordings of 24-hour intragastric pH could be obtained with antimony and glass electrodes in the same subjects. The reason for statistically insignificant differences of pH recordings with both electrodes in the early hours of the morning remains uncertain. The drift of glass and antimony electrodes did not differ. It is concluded from these data that, after adequate calibration, inferior electrochemical properties of antimony electrodes do not influence intragastric pH recordings in man. PMID- 2225519 TI - Standardization of electrode positioning and composition of meals for long-term intragastric pH metry in man. AB - In these prospective studies the influence of two different intragastric positions of electrodes and of four different compositions of standardized meals on 24-hour ambulatory pH recording were compared intraindividually in healthy male subjects. Simultaneous pH monitoring in 12 subjects demonstrated a more pronounced postprandial pH elevation in the fundus body compared to the antral area. The intraindividual comparison of an identical diet given on two different days to 10 subjects revealed nearly identical pH profiles. Variations of carbohydrate, protein and fat content of isocaloric meals given in a randomized order did not significantly alter 24-hour intragastric pH profiles. It is concluded from these data that positioning of the pH electrode in the fundus body area is superior to an antral position. 24-hour ambulatory intragastric pH monitoring in man is well reproducible. A strict standardization of the composition of meals is mandatory only for scientific investigations. PMID- 2225520 TI - Intragastric pH pattern analysis in patients with duodenogastric reflux. AB - The intention of the present study was to apply 24-hour intragastric pH monitoring as a diagnostic tool for the detection of pathologic duodenogastric reflux. Therefore, an evaluation system was developed which is able to recognize and quantify specific intraluminal gastric pH patterns regarding their specificity for the disease. pH parameters, stored during 24 h and processed, according to the evaluation system, were obtained for a healthy control population (n = 30) and for patients with pathologic duodenogastric reflux (n = 11). These data were subjected to computerized discriminant analysis to identify pH changes with a high probability of resulting from pathologic duodenogastric reflux. The computer analysis identified 16 discriminating pH parameters to separate a physiologic pH pattern from a 24-hour intragastric pH pattern with a high probability of being associated with pathologic duodenogastric reflux. PMID- 2225521 TI - Simultaneous measurement and recording of gastric potential difference and intragastric pH in man. AB - Gastric potential difference (GPD) is used increasingly as an index of mucosal integrity. The technique for GPD measurement currently employed is however laborious due to the preparation and check of KCl-agarose bridges prior to each experiment. In addition, calculations - usually handmade - are time-consuming and inaccurate. Therefore, a new apparatus allowing continuous recording of basal and drug-induced changes in GPD values was developed. A commercially available 24 hour pH monitor (Proxima Light, Synectics Medical) was modified in order to allow GPD measurement and recording with subsequent elaboration of data. Furthermore, simultaneous measurement of GPD and intragastric pH through the use of a single stomach probe was made possible. The new method was checked towards the classical PD measuring system employing KCl-agarose bridges. The readings obtained with both systems, either in basal conditions or after aspirin, correlated in a highly significant way. Readings proved to be quite stable with a variation, for 150 consecutive values, of less than 2 mV. With this system the effect of pH modifications, obtained through H2 receptor stimulation and inhibition, on the behaviour of GPD values was investigated in healthy volunteers. Analysis of paired data obtained from these experiments showed an inverse relationship between these two parameters. This suggests that GPD and pH should be measured together, especially during experiments aiming to study drug effects on gastric mucosa. Although the apparatus described was developed for PD measurement and recording in the stomach, it can be used easily for PD measurement across the mucosa of the entire digestive tract, for example in the esophagus, colon or rectum. PMID- 2225522 TI - Relationship between fluctuations of pH and pressure in the human stomach and duodenum. AB - The normal patterns of pressure activity in the antrum, pylorus and duodenum and associated pH changes were monitored in 9 healthy volunteers under fasted conditions and after ingestion of 300 ml of chocolate milk. The manometric assembly incorporated three side holes in the antrum, four side holes in the duodenum, a sleeve sensor positioned across the pylorus, and pH electrodes situated in the terminal antrum and proximal duodenum. The most common motor pattern recorded under fasting conditions consisted of regular co-ordinated contractions, most of which involved the antrum and duodenum, showed evidence of propagation and was associated with transient decreases in duodenal pH and transient increases in antral pH. Ingestion of milk changes the motor pattern to one that was composed of pressure waves which were confined to the pylorus with few or no pressure waves in the terminal antrum or proximal duodenum. Isolated pyloric pressure waves were gradually replaced by propagated antropyloroduodenal contractions which were associated with transient decreases in duodenal pH. Isolated pyloric pressure waves were not associated with episodes of duodenal acidification under fed conditions. PMID- 2225523 TI - Graphical display and statistical evaluation of data gained by long-term ambulatory intragastric pH monitoring. AB - The graphical display of data gained by long-term ambulatory intragastric pH monitoring requires different methods to present (1) the circadian time course of each individual, (2) data from all individuals belonging to the same group, and (3) data from two or more groups in a summary plot. Data reduction is normally required in all three cases; for this purpose, it is advisable to use median values from consecutive time periods, e.g. of 10-20 min each. All data from a total group of comparable individuals may be displayed using a pseudo-3D-graph allowing for easy recognition of interindividual variability. Summary curves from all data of one group may be gained by calculating medians from time-equivalent pH values and plotted together in one graph. The study design should take into consideration that intraindividual reproducibility of intragastric pH metry is excellent, while large variations may occur between individuals. Therefore, repeated measurements in the same individual under the different conditions to be tested are highly recommended. If two measurements are performed in each individual, the data are statistically evaluated using Wilcoxon paired rank test; Friedman rank test and subsequent multiple comparison according to Wilcoxon Wilcox are proposed in the case of more than two groups. Alternatively, multiple single tests may be used; this procedure, however, requires appropriate correction of the alpha-error which is best done using the exact versions of the test. PMID- 2225524 TI - Analysis and statistical evaluation of continuous pH recordings. PMID- 2225525 TI - Friedreich's ataxia: a descriptive epidemiological study in an Italian population. AB - All the cases of Friedreich's ataxia (FA) diagnosed between 1945 through 1984 among residents of a defined area of northwestern Italy were ascertained (N = 59). Cases were diagnosed according to the criteria of the "Quebec Cooperative Study on Friedreich's Ataxia (QCSFA)" with minor modifications. We identified 39 families with 47 probands and 12 secondary cases. Therefore ascertainment probability was 80%. Male to female ratio was 1:1. Pedigrees were compatible with autosomal recessive inheritance. Segregation ratio was 0.28 with both Weinberg's method and the "singles" method (under incomplete ascertainment). Point prevalence ratio was 1.2/100,000 population. Birth incidence rate was 1/36,000 live births. Gene frequency was estimated to be 1/191. The ratio of first-cousin marriages observed among parents of FA patients (3%) was lower than expected from Dahlberg's formula (8%). This finding is not compatible with the hypothesis of genetic heterogeneity for FA. PMID- 2225526 TI - Familial caudal dysgenesis: evidence for a major dominant gene. AB - Four sibs with varying degrees of caudal dysgenesis are described. Case 1 showed aberrant umbilical cord vasculature with a single umbilical artery near the placental insertion. Cases 2 and 3 showed full sirenomelia, one with a complex congenital heart defect. Case 4 had an imperforate anus and an excessively long umbilical cord. The father's half-sib had an imperforate anus, rectovaginal fistula and genitourinary anomalies. A dominant gene with reduced penetrance is likely. PMID- 2225527 TI - Phenotypic variability in Meckel-Gruber syndrome. AB - Five Bedouin sibs are described with Meckel-Gruber syndrome (MGS), an autosomal recessive disorder with multiple abnormalities. Each affected sib manifested only two of the three cardinal signs of MGS: occipital encephalocele and polycystic kidneys, lacking polydactyly. The phenotypic variability of the MGS pleiotropic gene is briefly discussed. PMID- 2225528 TI - Congenital cardiovascular malformations (CCVM) and structural chromosome abnormalities: a report of 9 cases and literature review. AB - Nine cases of congenital cardiovascular malformations (CCVM) with associated unbalanced structural chromosomal abnormalities were ascertained in a population based study of heart defects, constituting 0.4% of the 2,103 cases of CCVM in the Baltimore-Washington Infant Study (BWIS). This represents a four-fold increase over the general population rate. In an effort to determine possible phenotype/karyotype correlations, the literature was searched for cases with similar karyotypic abnormalities. This comparison of 223 literature cases of karyotypic abnormalities with nine similar cases ascertained by heart malformation has provided the opportunity to review cardiac defects reported in cases of structural abnormalities of chromosomes 1, 3, 7, 8, 9, 10, 11, 15, and 18. The most common cardiac malformation present in the chromosomal cases was ventricular septal defect (VSD) (39%); similarly VSD is the most common CCVM among children with heart defects, although it is the primary defect in only 20% of the BWIS cases. Among all heart defects in the BWIS, atrial septal defect (ASD) represents 5.5% of all cases, but in cases of 8p duplication, ASD is present in 41%. In addition, 40% of cases of 9p duplication had an ASD. Similarly, 35% of cases of 11q duplication had an ASD. While the suggestion of specific karyotype/phenotype association is premature, information on additional cases might clarify the possibility that genetic determinants related to septum formation may reside on chromosome 8, 9, and/or 11. The variety of chromosomal abnormalities in cases with ventricular septal defect indicates one type of genetic heterogeneity that may be involved in this very common heart defect. PMID- 2225529 TI - An evaluation of 75 terminations of pregnancy based on abnormal laboratory findings at first trimester CVS. AB - Seventy-five selective terminations, based on abnormal laboratory findings at first-trimester CVS, were performed in 1581 consecutive pregnancies. In all cases a (semi-) direct method of cytogenetic analysis was used. The 75 abortions were analysed in number of ways. Confirmatory studies showed that three cases had to be considered as false-positive findings, and in one other case the results were inconclusive. Based on literature data, it was estimated that 41 of the 75 pregnancies would have resulted in seriously handicapped children, surviving beyond the age of 1 year, if no termination of pregnancy had taken place. Negative side-effects of the procedure include: spontaneous abortion of chromosomally normal fetuses due to the CVS procedure itself and the need for a number of secondary amniocenteses (5.1%). The advantage of DNA diagnosis in X linked diseases is illustrated by comparing the CVS results with a previously published amniocentesis study. PMID- 2225530 TI - Activity of glucocerebrosidase in extracts of different cell types from type 1 Gaucher disease patients. AB - Glucocerebrosidase activity in extracts of leukocytes, Epstein-Barr virus transformed lymphocytes and fibroblasts from Portuguese Type 1 Gaucher disease patients was studied. The residual glucocerebrosidase activity in all extracts from patients was less than 25% if measured in the presence of bile salt taurocholate. However, if measured in the absence of bile salt the residual enzyme activity in extracts from patients was cell type specific: it was severely reduced in the case of fibroblasts, mildly reduced in the case of lymphoblasts and not significantly reduced in the case of leukocytes. The glucocerebrosidase activity in extracts from all control cell types was stimulated by taurocholate. In the patients the enzyme activity in fibroblasts extracts was also stimulated but that in lymphoblasts and leukocytes was inhibited by the bile salt. The differences in glucocerebrosidase activity (in the absence of taurocholate) in extracts from different cell types from Gaucher disease patients are attributable to differences in the proportion of glucocerebrosidase present as a monomer with low activity (form I) and as a highly active aggregate (form II) that may also contain sphingolipid activator protein 2 (SAP-2). In extracts from leukocytes and lymphocytes from Type 1 Gaucher disease patients, but not in those from fibroblasts, a relatively high proportion of enzyme is present in aggregated form with near normal specific activity. PMID- 2225531 TI - Lacrimo-auriculo-dento-digital (LADD) syndrome with renal and foot anomalies. AB - A patient who presented with most features of lacrimo-auriculo-dento-digital (LADD) syndrome, an autosomal dominant trait, is described. There was no deafness, and anomalies of the external ear and the upper limbs were discrete. Renal anomalies, consisting of progressive caliectasis with stone formation, were revealed by macroscopic hematuria. There were also skeletal anomalies of both feet, a feature not previously described. Renal and distal limb anomalies are probably features of LADD syndrome. PMID- 2225532 TI - Frontonasal dysplasia or craniofrontonasal dysplasia and the Poland anomaly? AB - We describe a 10-year-old girl with features of a frontonasal dysplasia and a right-sided Poland anomaly. As there has been one previous case report of pectoral muscle hypoplasia in association with craniofrontonasal dysplasia, the relationship between these two conditions is discussed. PMID- 2225533 TI - The second family with Spahr-type metaphyseal chondrodysplasia: autosomal recessive inheritance confirmed. PMID- 2225534 TI - Childhood sexual abuse--a dermatological perspective. PMID- 2225535 TI - Lichen planus in children--a review of six cases. AB - We present the features of six children who have been seen amongst 154 consecutive new patients with lichen planus in our outpatients clinic. All but one of the children had unusual forms of the disease and there was a family history of lichen planus in three. Lichen planus is rare in childhood and often assumes atypical clinical patterns. PMID- 2225536 TI - Ranking of the antipsoriatic effect of various topical corticosteroids applied under a hydrocolloid dressing--skin-thickness, blood-flow and colour measurements compared to clinical assessments. AB - In 10 patients with chronic plaque type psoriasis one or two plaques affected equally with psoriasis were chosen for study. Five punched out rings of a hydrocolloid dressing were applied to the psoriasis plaque(s). In each circular test area 20 mg of one of the following creams was applied: base, 1% hydrocortisone (DAK), 0.1% triamcinolone acetonide (Kenalogue), 0.1% betamethasone-17-valerate cream (Betnovate), and 0.05% clobetasol proprionate cream (Dermovate). The areas were occluded with a thin film of transparent hydrocolloid dressing (Comfeel Transparent Dressing), for 1 week. Non-invasive measurements (ultrasound skin thickness, laser-Doppler flowmetry, colorimetry) were performed before and after treatment. Therapeutic response was evaluated blindly by clinical score. The measurements showed a decline in blood flow, a decrease in skin thickness, and normalization of colour approaching that of normal skin, the more potent the corticosteroid used. The clinical scores showed the same: the more potent a corticosteroid used, the closer to the score of normal skin. Data on variability and applications of the methods are presented. The study concludes that potent corticosteroids occluded with a hydrocolloid dressing can clear psoriasis in 1 week. Short-course corticosteroid therapy appears harmless and relevant for clinical dermatology. PMID- 2225537 TI - Unilateral naevoid basal-cell-carcinoma syndrome--an individually controlled study of fibroblast sensitivity to radiation. AB - A patient with unilateral naevoid basal-cell-carcinoma syndrome (NBCCS, Gorlin's syndrome) provided a unique opportunity to compare the radiation sensitivity of fibroblasts from the affected and unaffected sides of the same individual. Although the growth rate of the fibroblast strain established from the affected side was faster than that from the unaffected side there was no difference in X ray, UV-B or UV-C radiation sensitivity between fibroblasts from the two sides. These results are discussed in the context of previous studies of radiation sensitivity in NBCCS. PMID- 2225538 TI - Introital adenosis associated with the Stevens-Johnson syndrome. AB - A young woman presented with erosive lesions of the labia minora, which appeared 3 years ago after Stevens-Johnson syndrome. Pathological examination showed 'vulval adenosis'. A similar case has been previously reported. Vaporization by carbon-dioxide laser gave satisfactory results, and after 2 years the patient remains totally cured. We discuss several embryological theories which may explain the mechanism of the vulval adenosis in this patient. PMID- 2225539 TI - Methotrexate and trimethoprim-sulphamethoxazole--a potentially hazardous combination. AB - A 74-year-old woman had been treated with methotrexate over 2 years for rheumatoid arthritis. She was admitted to the hospital because of non-healing leg ulcers. After being treated with trimethoprim-sulphamethoxazole for a urinary tract infection, she developed severe pancytopenia, followed by pneumonia and septic shock. The patient died shortly after. Concomitant treatment with methotrexate and sulphonamides should be strongly discouraged. PMID- 2225540 TI - Mosaic acral keratosis. AB - We describe two patients with acral keratosis with a striking mosaic or jigsaw puzzle pattern of keratotic papules on the dorsal aspects of the feet and adjacent parts of the legs. Both patients also showed mild diffuse palmoplantar keratosis and clavus-like lesions over the interphalangeal joints of the toes; one patient also had keratotic papules on the hands and hyperkeratotic plaques over the knees. The differential diagnosis of acral keratoses, including several recently described forms, is briefly discussed. PMID- 2225541 TI - UV-B-induced bullous pemphigoid restricted to mycosis fungoides plaques. AB - We describe a 77-year-old female patient with plaque-stage mycosis fungoides (MF) who developed bullous lesions in lesional skin only, while receiving short-wave ultraviolet radiation (UV-B) therapy. Histopathological and immunohistochemical examination resulted in a diagnosis of bullous pemphigoid (BP). Withdrawal of the UV-B treatment and application of a high-potency topical corticosteroid cream resulted in a rapid regression of the BP. As the bullous lesions were strictly confined to the MF plaques, the cutaneous infiltrate was probably involved also in the development of the BP. To our knowledge, this is the second case report of the coexistence of MF and BP and the first one in which the BP might be UV-B induced. PMID- 2225542 TI - Chronic bullous disease of childhood in three patients of Polynesian extraction. AB - Chronic bullous disease of childhood is an acquired subepidermal bullous disease. Its true incidence is unknown and to our knowledge there have been no reported cases in Polynesians. We report three cases who presented within 1 year to the Dermatology Department, Auckland Public Hospital, New Zealand. PMID- 2225543 TI - Adult xanthogranulomatosis associated with abnormal plasma apolipoprotein levels. AB - A case of adult xanthogranulomatosis was investigated in depth for lipid abnormalities. The xanthogranulomatous lesion was shown to be composed primarily of cholesterol esters and triglycerides. Fasting plasma lipid levels and lipoprotein concentrations were within normal limits. Plasma lipoprotein electrophoresis and immunoelectrophoresis demonstrated normal high-density lipoprotein (HDL) and low-density lipoprotein mobilities. Polyacrylamide-gel isoelectric-focusing electrophoresis revealed increased levels of very-low density apolipoprotein (apo) E, especially apo E-III. In the HDL fraction, apo-C III and apo-E levels were both found to be slightly elevated. These findings might imply a causal relationship between the abnormal plasma apolipoprotein levels and the xanthogranulomatous disease. PMID- 2225544 TI - Arthro-osteitis with palmoplantar pustulosis. PMID- 2225545 TI - Rippled hyperpigmentation resembling macular amyloidosis--a feature of atopic eczema. AB - We present a patient with long-standing refractory atopic eczema who developed a pattern of lichenification and hyperpigmentation resembling macular amyloidosis. Histology showed changes of chronic lichenification only. We suggest that this appearance is a feature of her eczema rather than amyloidosis. PMID- 2225546 TI - Orofacial granulomatosis associated with delayed hypersensitivity to cobalt. AB - Orofacial granulomatosis is a distinct clinical and pathological entity characterized by swelling of the lips and lower half of the face. Ulceration of the oral mucosa may also occur. Granulomas are seen histologically. Orofacial granulomatosis may occur in the Melkersson-Rosenthal syndrome, granulomatous cheilitis of Miescher, oral Crohn's disease, sarcoidosis and focal dental sepsis. The increased prevalence of atopy in patients with orofacial granulomatosis and the association with food intolerance suggests the possibility of a role for allergy in at least some cases. PMID- 2225547 TI - Pulsed 2.94-microns erbium-YAG laser skin ablation--experimental results and first clinical application. AB - In the present study we compared skin-ablative effects produced by 2.94-microns pulsed erbium-YAG radiation on pig skin with those of the pulsed 308-nm UV excimer laser, continuous-wave CO2 laser, electrocautery and cold-knife surgery. Pulsed 2.94-microns radiation led to clean ablation craters and precise cuts with only minimal adjacent tissue damage followed by excellent healing without apparent scarring. These experimental results are consistent with those obtained from first clinical applications in the treatment of epidermal naevi and tattoos. However, since coagulation was insufficient to prevent bleeding and because of low repetition rates provided, the Er-YAG lasers currently available seem as yet of limited value for effective removal of deeper or larger lesions. PMID- 2225548 TI - Erythema elevatum diutinum--a solitary lesion in a patient with rheumatoid arthritis. AB - Erythema elevatum diutinum is a rare disease of unknown aetiology. It is usually symmetrical with multiple lesions. An association with rheumatoid has previously been reported. We report a case of atypical erythema elevatum diutinum affecting the right elbow of a female patient with seropositive rheumatoid arthritis. PMID- 2225549 TI - Localized scleroderma--response to 1,25-dihydroxyvitamin D3. AB - 1,25-Dihydroxyvitamin D3 [1,25(OH)2 D3] may be an immunomodulatory drug which could have a role in controlling collagen deposition, and inducing reversal of fibrosis in some tissues. These observations prompted a study of the possible use of this hormone for the treatment of scleroderma. A 35-year-old woman, who had been suffering from localized scleroderma for 2 years, was given oral 1,25(OH)2 D3 for 6 months. The effects of the treatment were evaluated using clinical and physical measurements (skin thickness, extensibility properties of the skin). The evolution of the patient's condition during the 6-month therapy suggests that 1,25(OH)2 D3 is beneficial in localized scleroderma. The mechanisms of action are discussed in relation to the literature, which suggests both immunoregulatory and inhibitory effects on fibroblast growth. PMID- 2225551 TI - Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists. 24th annual scientific meeting, 10-12 December 1990, Victoria. Abstracts. PMID- 2225550 TI - Oxygen consumption in psoriasis. PMID- 2225552 TI - Comparison of pathological lesions on repeated renal biopsies in 73 patients with primary IgA glomerulonephritis: value of quantitative scoring and approach to final prognosis. AB - In order to improve our possibility of establishing a long-term prognosis in IgA nephritis, 73 patients out of a cohort of 282, followed over a mean period of 12 years at the same institution for an IgA nephritis, had a prospective second renal biopsy 5 years later. For all biopsies (RB1 and RB2), we developed a quantitative scoring for all elementary lesions with a glomerular, an interstitial, a tubular and a vascular index. The sum of these 4 indexes gave a global optical score (GOS). Pathological improvement on light microscopy (delta GOS less than or equal to -2) was noticed only in 3 patients (4%), stability (-2 less than delta GOS less than +2) in 30 patients (41%), mild deterioration (+2 less than or equal to GOS less than 5) in 23 patients (32%) and major progression (delta GOS greater than or equal to 5) in 17 patients (23%). We observed no pathological remission, even in the 14 patients with complete clinical remission. The pathological progression was characterized by an increase in all elementary lesions, mainly the tubulo-interstitial and vascular ones. By immunofluorescence mesangial IgA deposits remained stable with no disappearance; however, the number and intensity of vascular C3 deposits were significantly greater on RB2. Chronic renal failure (serum creatinine greater than 1.5 mg/dl) correlated best with major pathological progression and mainly with the progression of extraglomerular lesions. IgA nephritis is a slowly progressive disease with no pathological remission, and its evolution is characterized by progression of extraglomerular lesions, mainly vascular, which might play a major role in the ultimate development of chronic renal failure. PMID- 2225553 TI - IgA nephritis in Behcet's disease: case report and review of the literature. AB - We describe a 13-year-old girl with the incomplete type of Behcet's disease who had recurrent oral and genital ulcers, folliculitis, proteinuria and hematuria. Renal biopsy specimens revealed diffuse proliferative glomerulonephritis with strongly positive IgA deposits in the glomerular mesangial area, which is histologically indistinguishable from primary IgA nephritis. Further studies of the IgA subclasses showed that IgA1 deposits were predominant in the glomerular mesangium. Primary IgA nephritis is thought to be associated with polymeric IgA1. So it appears that there may be a common underlying disease or mechanism involved in both primary IgA nephritis and the IgA nephritis in Behcet's disease. PMID- 2225554 TI - Glomerular IgA deposits in patients with celiac disease. AB - Glomerular immunopathology was studied in 25 patients with newly diagnosed celiac disease. None had clinical signs of renal disease. Glomeruli were obtained by fine-needle aspiration biopsy. The specimens were processed and studied by indirect immunofluorescence for immunoglobulins and complement. Mesangial IgA was found in 8 of the patients. It occurred occasionally together with slight IgG or IgM, but C3 was not seen in these patients. IgA-class circulating immune complexes (CIC), antireticulin antibodies (ARA), antigliadin antibodies (AGA), and rheumatoid factor (RF) occurred significantly more often in the patients with mesangial IgA than in the 17 patients having no mesangial IgA. The patients with mesangial IgA also had significantly higher mean levels of serum IgA, IgA-ARA and IgA-AGA than those without. The results suggest that glomerular mesangial deposits of IgA occur frequently in untreated celiac disease and that they are in some way associated with circulating IgA-class antibodies and immune complexes. In this situation IgA seems to be deposited without being able to induce clinically overt glomerulonephritis, a circumstance that may be related to the lack of complement in the deposits. PMID- 2225555 TI - Diffuse proliferative lupus nephritis: long-term observations in patients treated with ancrod. AB - Twenty-two patients with histologically demonstrated diffuse proliferative lupus nephritis (DPLN) and glomerular thrombosis received a 14-day course of ancrod, followed in most by nitrogen mustard (mechlorethamine hydrochloride) 0.4 mg/kg. Many were referred when renal function was deteriorating despite large doses of prednisone. The patients had severe disease; there was a high degree of glomerular sclerosis; the median serum creatinine was 137 mumol/l, the diastolic blood pressure 101 mm Hg. Reported previously was a short-term improvement in renal function, blood pressure, and renal histology. Reported here is the long term follow-up on all 22 patients for an average of 58 months. Three died of causes other than renal failure. Eleven developed end-stage renal disease an average of 27 months after ancrod treatment. The other 8 are alive with no deterioration of renal function after an average of 70 months. This outcome seems satisfactory when disease severity is taken into consideration. Factors present at treatment start that might be associated with subsequent renal function deterioration were: prior prolonged prednisone treatment, extensive glomerular sclerosis, high plasma alpha 2-antiplasmin and possibly triglycerides. During the follow-up period after completion of treatment, later relapses of SLE and DPLN appeared to be an important predictor of deterioration of renal function. PMID- 2225556 TI - Disappearance of renin-induced proteinuria by an ACE-inhibitor: a case report. AB - A 55-year-old man developed renovascular hypertension that was characterized by high plasma renin activity. This was accompanied by nephrotic range proteinuria. Treatment with nifedipine and furosemide lowered the blood pressure to normal values, but proteinuria persisted. However, treatment with an ACE-inhibitor brought resolution of the proteinuria, suggesting a role for angiotensin II in urinary protein loss. PMID- 2225557 TI - Post-traumatic acute renal failure, 1956-1988. AB - Eighty patients with acute renal failure secondary to trauma treated between 1956 and 1988 are reviewed. The overall mortality was 46.3%. Factors associated with increased mortality were age, high Injury Severity Score, and injury to the abdomen and pelvic contents. The number of injuries, the delay between injury and the institution of dialysis, and the level of urea on starting dialysis did not affect mortality. The declining incidence of traumatic acute renal failure highlights the importance of prompt effective resuscitation of injured patients. PMID- 2225558 TI - Changes in intact parathyroid hormone levels during hemodialysis following exposure to either differing dialyzate calcium concentrations or calcium-free dialysis with varying calcium infusion rates. AB - To determine the optimal infusion rate for calcium, when using a dialyzate which was calcium free, six patients were treated sequentially, in random order, with six different dialyzates. Three were calcium free and they were infused with replacement calcium at either 10, 15 or 20 ml/hour using 10% CaCl2. The other three used standard bicarbonate dialyzate with either 1.25, 1.5 or 1.75 mmol/l calcium. Ionized calcium and intact parathyroid hormone (Nichols IRMA PTH) were measured at the start and end of each dialysis. Ionized calcium rose slightly with 15 ml/hour calcium infusion and PTH fell 137 +/- 111 pg/ml. These changes were similar to those of 1.5 mmol/l calcium in standard bicarbonate. More PTH suppression and higher end dialysis calcium resulted from 20 ml/hour infusion or 1.75 mmol/l dialyzate calcium. It was concluded that 15 ml/hour is a suitable calcium infusion rate under normal conditions when using calcium-free dialyzate. PMID- 2225559 TI - Lack of effect of captopril in cystinuria. PMID- 2225560 TI - The treatment of mesangial IgA nephropathy with cyclophosphamide, dipyridamole and warfarin: a two-year prospective trial. AB - Of 52 patients with mesangial IgA nephropathy, 25 were allocated to treatment with cyclophosphamide (6 months), and dipyridamole and warfarin (2 years) and 27 to no treatment in a randomized prospective 2-year study. At entry, the treated and untreated groups of patients did not differ in mean serum creatinines, urinary protein excretions, quantitative urinary erythrocyte counts or blood pressure readings. At the end of the trial mean (+/- SEM) serum creatinine values had gone from 0.12 +/- 0.01 to 0.13 +/- 0.01 mmol/l (p less than 0.05) in untreated patients and from 0.10 +/- 0.01 to 0.12 +/- 0.01 mmol/l (p less than 0.05) in treated patients. Mean (+/- SEM) log values of urinary erythrocyte (rbc) counts had not changed significantly from 5.47 +/- 0.09 to 5.21 +/- 0.14 log rbc/ml in untreated patients, from 5.45 +/- 0.11 to 5.49 +/- 0.19 log rbc/ml in treated patients. However, in treated patients, mean (+/- SEM) urinary protein excretions decreased from 1.67 +/- 0.35 to 1.15 +/- 0.31 g/24 h (p less than 0.01) whereas in untreated patients urinary protein was unchanged between initial values of 1.76 +/- 0.34 and follow-up at 1.89 +/- 0.45 g/24 h. No significant changes in blood pressure occurred in either group. This study supports the observation that treatment of IgA nephropathy with cyclophosphamide, dipyridamole and warfarin is associated with a reduction of urinary protein excretion but a significant effect on preservation of renal function, at least as determined by serum creatinine values, could not be confirmed over this two-year study. PMID- 2225561 TI - Membranous glomerulonephritis induced by 2-mercaptopropionylglycine (2-MPG). AB - Thirty-two patients suffering from cystinuria were treated with 2 mercaptopropionylglycine (2-MPG) for 0.5-10 years (average 6.3 years). After 4-14 months of treatment at daily doses ranging from 500 to 2500 mg, three patients developed slight to moderate proteinuria. Two patients were subjected to renal biopsy which showed membranous glomerulonephritis. In one biopsy signs of progressive glomerular lesions were observed. In seven patients (22%) antinuclear antibodies were demonstrated. In one patient with biopsy-proven membranous glomerulonephritis, the antinuclear antibodies consisted of antihistone antibodies. The observations presented in this report indicate that 2-MPG, like D penicillamine, could induce autoimmune reactions, in some cases leading to membranous glomerulonephritis. The prognosis seemed to be favorable. However, the occurrence of irreversible glomerular lesions as reported by us should be borne in mind when considering long-term treatment with 2-MPG. A continuous, close follow-up of patients on 2-MPG treatment is recommended. PMID- 2225562 TI - Acute deterioration of renal function associated with enteric hyperoxaluria. AB - Enteric hyperoxaluria due to malabsorption syndromes has been well documented to cause renal calculi and chronic tubulointerstitial renal damage. Rarely, in the setting of intestinal bypass operations for morbid obesity, enteric hyperoxaluria has produced acute renal failure. We report two patients who suffered acute deterioration of renal function associated with increased intestinal absorption and renal excretion of oxalate associated with steatorrhea. One patient had a large portion of his small bowel resected many years prior to the onset of the renal failure and the second patient had chronic pancreatitis causing steatorrhea. Both patients had renal biopsy documentation of the acute nature of the tubular damage produced by oxalate deposition. The mechanisms of their deterioration of renal function may relate to sudden increases in steatorrhea in association with episodes of volume depletion. Enteric hyperoxaluria may be an easily overlooked and potentially preventable etiology of acute renal dysfunction. PMID- 2225563 TI - Is preliminary binephrectomy necessary in patients with autosomal dominant polycystic kidney disease undergoing renal transplantation? AB - Patients with end-stage chronic renal failure due to autosomal dominant polycystic kidney disease who underwent renal transplantation with or without preliminary binephrectomy were retrospectively studied to determine the effect of binephrectomy on outcome. Nineteen patients were identified. Thirteen patients had no surgery prior to transplantation and six underwent preliminary binephrectomy. One patient died as a result of the nephrectomy. Twenty-one renal allografts were performed on 18 patients of whom seven have died of sepsis; 10 have functioning grafts and one has returned to dialysis. Patients not undergoing preliminary binephrectomy had a statistically significant (p less than 0.05) increase in mortality and morbidity due to septic complications related to polycystic kidney disease. Indications for bilateral nephrectomy should be reconsidered. PMID- 2225564 TI - Hypophosphatemia in infants on continuous ambulatory peritoneal dialysis. AB - Three infants with irreversible renal failure and treated with continuous ambulatory peritoneal dialysis (CAPD) developed hypophosphatemia. In one of them rachitic lesions were observed on X-ray and bone biopsy showed osteomalacic osteodystrophy. Different mechanisms may have been at the origin of the hypophosphatemia: high doses of phosphate binders, low phosphorus intake, phosphate loss with the dialysate and possibly nutritional repletion. Dietary phosphorus restriction and use of phosphate binders should be applied with caution and serum phosphate should be monitored regularly in infants treated with CAPD. PMID- 2225565 TI - SLE nephritis: an ultrastructural immunogold study to evaluate the relationship between immune complexes and the basement membrane components type IV collagen, fibronectin and heparan sulphate proteoglycans. AB - The nature of immune complexes and their relationship to the normal glomerular basement membrane (GBM) components type IV collagen, fibronectin, and heparan sulphate proteoglycans (HSPG) have been examined in the glomeruli of 7 cases of systemic lupus erythematosus (SLE) glomerulonephritis using an ultrastructural immunogold technique. In paraformaldehyde-fixed, Lowicryl resin-embedded tissue, the electron-dense deposits contained IgG, IgM, IgA, and C3 whether they were subepithelial, intramembranous, subendothelial, or mesangial and there was no particular relationship between the class of immunoglobulin and site of immune complex localization within the glomerulus. The normal GBM components type IV collagen, fibronectin, and HSPG were found within all the glomeruli, but did not have the same distribution. Type IV collagen and fibronectin were found predominantly on the inner aspect of the GBM and diffusely throughout the more central regions of the mesangial matrix. By contrast the HSPG was seen mainly on the outer aspect of the GBM and at the periphery of the mesangial matrix. In none of the cases were GBM antigens localized within the electron-dense deposits, results which suggest that autoantibodies to these GBM components may not play a role in the development of the glomerulonephritis. PMID- 2225566 TI - In vitro effects of bone- and platelet-derived transforming growth factor-beta on the growth of Walker 256 carcinosarcoma cells. AB - Conditioned media from fetal rat calvarial cultures has previously been shown to stimulate the growth of the bone-metastasizing Walker 256 carcinosarcoma cell line. In the current investigation we looked at the possibility that transforming growth factor-beta (TGF-beta), present in conditioned media, and positively correlated with resorption in vitro, may be responsible for the enhanced proliferation of Walker cells cultured in these conditioned media. Purified platelet-derived TGF-beta produced a dose-dependent growth response in Walker cells with an ED50 equal to 0.05 ng/ml. Bone-derived TGF-beta activity in conditioned media, measured by NRK fibroblast colony formation, correlated well with percentage resorption in bone cultures, and growth activity in Walker cell culture. In addition to this, the growth response normally seen with conditioned media cultures of Walker cells was significantly inhibited by the addition of anti-TGF-beta 1 neutralizing antibody. We conclude that TGF-beta is an important growth stimulatory component from fetal rat calvaria. PMID- 2225567 TI - Immunotherapy of the rat 13762SC mammary adenocarcinoma by vaccinia virus augmentation of tumor immunity. AB - We studied whether vaccinia virus (VV) functioned as an immunogenic carrier in augmenting anti-tumor immunity in rats bearing a syngeneic metastatic tumor. The primary tumor was induced by injecting 10(6) 13762SC mammary adenocarcinoma cells subcutaneously into the right hind footpad of Fischer 344 rats. A concomitant anti-tumor response is induced by the tumor as demonstrated by the inhibited growth of a second tumor challenge given in the contralateral footpad 3-15 days later. Attempts were made to increase the concomitant immunity by injecting tumor bearing animals intramuscularly with irradiated, VV-infected or uninfected 13762SC cells without adjuvant. Provided the immunotherapy was done within 5 days of the tumor challenge, administration of 10(6)-10(7) irradiated, VV-infected 13762SC cells resulted in significantly slower tumor growth, or led to complete tumor regression, compared to control animals given no treatment. In contrast, tumor growth in animals given only VV or given irradiated, uninfected 13762SC cells, alone or mixed with VV, was the same as that in control animals. Kinetics of early primary tumor growth were predictive of a longer-term anti-tumor effect. Rechallenge of 13762SC tumor-cured animals with either the homologous or with a heterologous syngeneic mammary adenocarcinoma showed the animals to be specifically 13762SC tumor-resistant, since only rats challenged with the heterologous mammary adenocarcinoma developed progressive tumors. We interpret these results to mean that early immunotherapy with irradiated, VV-infected 13762SC cells enhances an on-going anti-tumor immune response sufficiently to cause rejection of the primary tumor and any metastases that have occurred. We also believe that later immunotherapy with irradiated, VV-infected cells has no effect due to tumor-induced immunosuppression becoming paramount. PMID- 2225570 TI - Annual meeting of the Canadian Cardiovascular Society. October 17-20, 1990, Halifax, Nova Scotia. Program and Abstracts. PMID- 2225571 TI - Obstetric emergencies. PMID- 2225568 TI - Tumor progression- and metastasis-associated proteins identified using a model of locally recurrent rat mammary adenocarcinomas. AB - A recently established model for local breast cancer recurrence using the 13762NF rat mammary adenocarcinoma was used to evaluate biologic and biochemical properties related to clinical outcome for this class of tumors. Sublines isolated from local tumor regrowths following surgical resection differed from each other and from the 'parental' cell lines for multiple phenotypes, including metastatic propensity. Local recurrence- and primary tumor-derived sublines were examined by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), lectin binding to electrophoretically separated proteins, and lactoperoxidase-catalyzed cell surface iodination; and differential protein patterns were compared to tumor progression and metastatic potential. 2D-PAGE revealed several quantitatively different spots which correlated with lung colonization potential. In particular, quantities of an apparently unique, non-cell-surface protein, P50.9 (Mr approximately 50,900, pI approximately 7.3) correlated inversely with metastatic propensity, suggesting that it may be associated with, among other possibilities, the negative regulation of the metastatic phenotype. P50.9 was unrelated to four similarly sized metastasis-associated proteins--tumor autocrine motility factor; the rat analog of tumor suppressor, p53; rat cytokeratin 14 or procathepsin D--as determined by amino acid analysis. A major wheat germ agglutinin binding sialoglycoprotein, gp93 (Mr approximately 93,000), was present in smaller amounts as cells were passaged in vivo and re-established as in vitro cultures [MTF7 greater than 'primary' tumor-derived lines (sc1, sc3) much greater than local recurrence-derived lines (LR1, LR1a, LR3, LR4, LR5, LR6)]. Besides cell surface glycoprotein losses, two of six local recurrence-derived sublines expressed a wheat germ agglutinin-binding sialoglycoprotein, gp110 (Mr approximately 110,000), previously undetected on any of the other cell lines including the parental populations. gp110 was found in LR3 and LR6 which were relatively highly metastatic; however, correlation with metastatic potential failed because gp110 was not present on the metastatic parental cell line, MTF7. These results demonstrate specific quantitative and qualitative protein differences associated with the selection of locally recurrent mammary tumors. PMID- 2225569 TI - Measurement of DNA content and nuclear pleomorphism in metastatic variants of the B16 murine melanoma and hamster lymphoma and its liver metastasis using image analysis techniques. AB - The DNA content and nuclear pleomorphism (NPM), which are two cellular features consistently employed in the assessment of tumour malignancy, have been measured in B16 murine melanoma metastatic variants and in hamster primary lymphoma and its liver metastasis as tumour models using image analysis techniques. The three melanoma variants studied were the low metastasis variant F1, the BL6 variant selected for high lung metastasis and invasive ability, and ML8, a line isolated from pulmonary metastasis of the BL6 tumour. The cellularity of the melanomas bore no relationship to metastatic ability. The cell cycle distribution of nuclei based on integrated nuclear density (IND) was studied. The ML8 tumour showed higher DNA ploidy. Also, in this tumour the S-phase fraction was approximately 2.0-fold larger than that of the BL6 tumour. Flow cytometry of nuclei isolated from paraffin-embedded tumour tissue showed all three melanomas were aneuploid. In both F1 and BL6, two distinct subpopulations (p2 and p3) of nuclei, based on the degree of their pleomorphism, could be discerned. A significantly higher proportion of the more pleomorphic subpopulation (p2) occurred in BL6 than in F1. In the ML8 alone, a third subpopulation (p1), which was more pleomorphic than p2, was found. The hamster lymphomas (HALY-malignant and N-HALY-non-malignant) were less cellular than the metastatic tumour (HALY-met) in liver. The lymphomas N HALY and HALY-met had a higher DNA ploidy as compared with its primary tumour HALY. However, the non-malignant lymphoma N-HALY and the moderately malignant hamster fibrosarcoma were also found to be hyperdiploid. The metastatic lymphoma (HALY-met) showed a more pleomorphic nuclear subpopulation as compared with the primary. No differences were found in the size of the S-phase fractions of the hamster tumours. The present work shows that image analysis techniques enable one to make objective measurements of DNA content and nuclear pleomorphism of tumour cells, and suggests that in the tumour models investigated there is increased nuclear pleomorphism and DNA ploidy associated with tumour progression. PMID- 2225572 TI - Placenta previa. AB - A placenta previa, whether found fortuitously by ultrasound or with the clinical emergency of maternal hemorrhage, carries significant maternal and fetal risk. Accurate diagnosis, judicious expectant management with transfusion as required, and delivery at the time of fetal lung maturation can lead to the most favorable outcome. Anticipation of the clinical complication of placenta accreta may avoid some serious consequences. Clinical judgement and skill in the performance of cesarean sections, dilatation and curettage, and other forms of uterine invasive techniques may help to keep subsequent incidence of placenta previa at a reasonably low rate. PMID- 2225573 TI - Postpartum hemorrhage: placenta accreta, uterine inversion, and puerperal hematomas. AB - Puerperal hematomas, although rare, can be potentially morbid or life-threatening events. Early surgical management, including clot evacuation, layered closure, drainage, antibiotics, and fluid replacement (including blood), usually result in satisfactory outcome. Prevention is clearly preferable and often achievable with careful initial repair of episiotomies and lacerations. PMID- 2225574 TI - Uterine rupture. AB - Uterine rupture is a sudden, unforeseeable event that carries a high rate of maternal and perinatal mortality. When the diagnosis of uterine rupture is suspected, prompt surgical intervention with an experienced pelvic surgeon and blood product replacement should be considered. At the time of uterine rupture, the patient should be evaluated for possible repair or hysterectomy. It appears, based on the aforementioned information, that repair is a reasonable consideration. In those patients who have undergone a repair, early delivery by elective cesarean after assessment of fetal lung maturity at or around 36 weeks gestation would appear prudent. In those patients with a prior cesarean, continuous electronic fetal monitoring to detect intrapartum fetal distress would appear prudent. In these patients fetal distress is the most common sign or symptom of uterine rupture and frequently precedes any other clinical manifestations of this complication. PMID- 2225575 TI - Emergent management of abdominal pregnancy. PMID- 2225576 TI - Ectopic pregnancy: a look at changing concepts and problems. PMID- 2225577 TI - Hypovolemia due to hemorrhage. PMID- 2225579 TI - Cerebrovascular emergencies in pregnancy. PMID- 2225578 TI - Eclampsia. AB - Early detection and hospitalization in women with mild preeclampsia may prevent eclampsia. In the event of severe preeclampsia or eclampsia, delivery is indicated for the benefit of both mother and fetus. Thereafter, pathologic changes of preeclampsia and eclampsia, including major multiple organ system dysfunction, undergo complete reversal. PMID- 2225580 TI - Amniotic and thromboembolism. AB - Embolic phenomena in pregnancy demand rapid investigation and treatment. Regardless, some patients will not survive due to the enormity of the insult. Optimally, such patients should be treated in tertiary care centers, but this is not always possible. PMID- 2225581 TI - Obstetric septic shock: a pathophysiologic basis for management. PMID- 2225582 TI - Acute respiratory failure. AB - Pregnancy entails many unique physiologic changes that make the management of ARDS both challenging and unique. Most of these women are young and in excellent health before their acute injury, and their survival should exceed that of the general population who develop ARDS. We advocate aggressive management of the suspected lung injury including early intubation and the institution of invasive hemodynamic monitoring. This approach ensures the most thorough assessment of the extent of the initial injury and allows rapid assessment of therapeutic maneuvers and their subsequent adjustment. Our goal is to reverse the initial insult early while avoiding further iatrogenic injury. Optimal management of the maternal fetal pair requires the cooperation of an obstetrician well versed in cardiopulmonary physiology and physicians skilled in intensive care medicine. PMID- 2225583 TI - Preterm labor. PMID- 2225584 TI - Intrapartum assessment of fetal well-being. PMID- 2225585 TI - Shoulder dystocia. PMID- 2225586 TI - Reproductive endocrinology update. PMID- 2225587 TI - The ovarian follicle: life cycle of a pelvic clock. PMID- 2225588 TI - Reproductive steroid hormones: generation, degradation, reception, and action. PMID- 2225589 TI - Hormonal assay methodology: present and future prospects. PMID- 2225590 TI - Hyperprolactinemic disorders. PMID- 2225591 TI - Hyperandrogenic disorders. PMID- 2225592 TI - Polycystic ovary syndrome. PMID- 2225594 TI - Interhemispheric cysts in association with agenesis of the corpus callosum. AB - Two cases of complete agenesis of the corpus callosum each with large interhemispheric cysts are presented. The first case is an adult patient with chronic renal failure secondary to adult polycystic renal disease who was neurologically asymptomatic until she had a seizure during hemodialysis. The second case is an infant, who was diagnosed in utero as hydrocephalic, with severe mental and motor retardation and intractable seizures. The clinicopathologic findings in the two cases are presented, along with a discussion of the possible etiologies and clinical significance. PMID- 2225593 TI - Infantile inflammatory multisystem disease: clinicopathological findings and review of the literature. PMID- 2225596 TI - Medical induction of abortion. PMID- 2225597 TI - Termination of pregnancy--a global view. PMID- 2225595 TI - Aqueductal atresia as a feature of arhinencephalic syndromes. AB - Two cases are presented of aqueductal atresia associated with arhinencephalic syndromes. The first case was one of semilobar holoprosencephaly with occipital encephalocele, the second one of lobar holoprosencephaly (callosal agenesis with interhemispheric cyst). Only the second case was associated with obstructive hydrocephalus. The absence of hydrocephalus in the first case may be ascribed either to the greater distensibility of the encephalocele, or to the displacement of the choroid plexuses from the intracranial portion of the common ventricle into the hernial sac. PMID- 2225598 TI - Uterine contractility during pregnancy and the effect of abortifacient drugs. AB - There are a number of compounds in clinical use for termination of pregnancy. Treatment with all of them will result in increased uterine contractility. PGF2 alpha and PGE2 as well as different prostaglandin analogues all have a direct stimulatory effect on the myometrium, while other compounds such as hypertonic saline and Rivanol seem to act mainly through a stimulation of the endogenous production of PGF2 alpha. Treatment with antiprogestins which compete with progesterone at the receptor level or which inhibit progesterone biosynthesis results in an increased uterine contractility probably through a release from progesterone inhibition. If the withdrawal of progesterone also induces an increased endogenous prostaglandin production is unclear. The medical method to induce abortion which best resembles the physiological events during a spontaneous abortion is probably treatment with antiprogestins (receptor blockers or progesterone biosynthesis inhibitors) followed by prostaglandin. PMID- 2225599 TI - The physiology of cervical ripening and cervical dilatation and the effect of abortifacient drugs. AB - The mechanical properties of the human uterine cervix are determined mainly by the connective tissue component, whereas it is doubtful whether the scanty smooth muscle component is of any physiological importance. Histological and biochemical analyses reveal a fibrous connective tissue similar to that found in skin and tendon. Degradation of the collagen and an increase in some special dermatan sulphate proteoglycans can at least partly explain the pregnancy-associated softening of this connective tissue. Relatively high oestrogen levels seem to be an absolute condition for the process, even when it is induced pharmacologically. Treatment with progesterone-receptor blockers, PGE2, PGF2 alpha or relaxin in pregnancy induce cervical softening as well as histological and biochemical changes which cannot be distinguished from the physiological cervical softening which takes place in late pregnancy. Prostaglandins and relaxin might interact and could include cytokines such as interleukin-1 during the process. The effect of cervical tents cannot be explained only by the radial pressures they exert. Most probably stimulation of local prostaglandin synthesis is also involved. PMID- 2225600 TI - Post-ovulatory contraception. AB - It is possible to prevent pregnancy after unprotected intercourse by suppressing ovulation, inhibiting fertilization or interfering with tubal transport and/or implantation of the early embryo. IUCDs probably prevent implantation by stimulating the release of prostaglandins from the endometrium but are not acceptable to many women. Post-coital contraceptive steroids, e.g. high-dose oestrogens, are associated with a relatively high incidence of side-effects and must be taken within 72 hours of coitus. As these agents are effective by creating a uterine environment unfavourable for implantation, it may be possible to use antigestagens or antioestrogens in this way. It is already known that an antigestagen in combination with a prostaglandin is a highly effective method of inducing abortion in very early pregnancy. The corpus luteum is essential for the maintenance of pregnancy and its destruction by a luteolytic agent should dislodge the implanting embryo. If an effective method of preventing implantation could be developed which was relatively free from side-effects, it should be possible to use it as a regular form of contraception to be taken only when the risk of pregnancy had occurred. PMID- 2225601 TI - Medical methods to terminate early pregnancy. PMID- 2225602 TI - Pretreatment of the cervix prior to surgical evacuation of the uterus in the late first and early second trimester of pregnancy. PMID- 2225603 TI - Intrauterine administration of drugs for termination of pregnancy in the second trimester. AB - Medical methods have been used for many years to terminate mid-trimester pregnancy, ranging from irritant chemicals and traditional plants to ecbolic agents and solutions instilled locally into the uterus. These methods had serious limitations, with relatively high rates of maternal mortality and morbidity. Surgical evacuation requires special skills not available to all practitioners and many doctors consider second trimester dilatation and evacuation as a surgical taboo. In recent years several approaches evolved and reached the clinics, presenting safer and more effective options. Intra-amniotic instillation of hypertonic solutions, particularly saline or urea, proved in many hands to be a good method for pregnancies beyond 15 weeks of gestation. Due to a long latency period after instillation, these agents are often supplemented by an intravenous oxytocin infusion. Extraovular hypertonic saline or ethacridine (Rivanol) have their advocates, particularly in the grey-zone of pregnancy range from 13-15 weeks. In the last two decades, intrauterine prostaglandins were added to the methods in current use. Extra-amniotic prostaglandins (E2, F2 alpha or 15-methyl F2 alpha) were originally given in repeated doses or as a continuous local drip, but later a single instillation was used, usually mixing the drug with a viscous solution or gel. Intra-amniotic prostaglandins, in much higher doses, particularly the 15-methyl analogue, proved highly effective and relatively safe, especially when combined with laminaria tent insertion in the cervix. Various combinations of methods have provided a wide spectrum of data which is difficult to evaluate at present. Studies comparing different methods were mainly attempted in the mid-seventies. The outcome raised many pertinent questions and left many major issues unresolved. Most of the comparisons were not randomized or well controlled and only referred to the natural prostaglandin compounds. The analogues, however, seem to offer several advantages and the role of additional methods such as laminaria or antiprogestins remains to be further evaluated. PMID- 2225604 TI - Non-invasive methods for termination of second trimester pregnancy. PMID- 2225605 TI - Medical management of abnormal pregnancy. PMID- 2225606 TI - Acceptability of abortion methods. AB - This chapter has reported the findings of acceptability of prostaglandin pessaries compared with vacuum aspiration as methods for inducing abortion in a very early stage of pregnancy. Acceptability has been defined by the WHO as the degree with which a treatment method has attributes that make it perceived by a user or potential user to be consonant with his or her own sense of well-being and therefore will be used or preferred. The acceptability of the medical and surgical procedures for inducing abortion was studied in Swedish abortion patients using a pre- and post-abortion design for obtaining observations. Methods used included interview schedules, questionnaires, rating scales and attitude measuring techniques. Patients consenting to take part in the acceptability study had agreed to be randomly assigned to prostaglandin treatment, given at the clinic or self-administered by the patient at home, or to vacuum aspiration. A high degree of acceptability for the prostaglandin treatment was obtained in this group of patients who had applied for an abortion very soon after one missed menstrual period. This was indicated from the finding that the very high preference for this procedure remained unchanged in the group randomly assigned to it. Other measures of attitudes to prostaglandin treatment also indicated the unchanged positive attitude. There was a significant change in the attitude to vacuum aspiration among those assigned to this treatment, indicating that post-abortion it was more acceptable to these patients. However, 30% of them would still prefer the prostaglandin treatment, especially self-administered, in the event of another abortion. There were consistent and significant relationships found between the degree of negative emotional arousal before and after abortion and preference for the medical or surgical procedure and also the amount of complaints after abortion. Those patients who pre-abortion had preferred the self-administered procedure were, regardless of which treatment they had been assigned to, those who were least emotionally upset both before and after the treatment and also complained the least. This chapter also reported on findings of how acceptable the medical and surgical procedures can be inferred to be from comparisons of preferences and attitude measures obtained from abortion patients before treatment and from women in the same age group (who would not exclude an abortion if pregnant) in samples from outside the clinical setting. In the non-patient groups about half the subjects would prefer the medical alternative.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2225607 TI - The effect of pregnancy termination on future reproduction. AB - A variety of conditions have been anecdotally ascribed to induced abortion, including subsequent reproductive complications. Since most women obtaining induced abortions are at the beginning of their reproductive life, the effect of induced abortion on subsequent reproduction becomes a very significant one. Our review of the literature confirms findings reported previously. First, except in the case where an infection complicates induced abortion, there is no evidence of an association between induced abortion and secondary infertility or ectopic pregnancy. Second, the risk of midtrimester abortion, premature delivery and low birthweight in women whose first pregnancy is terminated by vacuum aspiration is not higher than that in women in their first pregnancy or women in their second pregnancy whose first pregnancy was carried to term. However, the risk of having a premature delivery or a low birthweight baby tends to be higher (but not significantly) among women whose first pregnancy is terminated by induced abortion when compared with women in their second pregnancy than when compared with women in their first pregnancy. This suggests that an induced abortion does not protect a women against the known risk of low birthweight for first-born offspring. Finally, women whose pregnancy is terminated by dilatation and evacuation may have an increased risk of subsequent premature delivery and a low birthweight baby. Very little has been published and no conclusions can be made regarding the effects of instillation procedures and repeat abortions on future reproduction. In conclusion, except for the association between pregnancies following dilatation and evacuation procedures and premature delivery and low birthweight, no significantly increased risk of adverse reproductive health has been observed following induced abortion. PMID- 2225608 TI - Future direction of abortion technology. AB - Reliable statistical data indicate that even today abortion is widely used in the regulation of human reproduction, irrespective of whether it is well or badly tolerated. Medical responsibility therefore dictates that abortions should be made as safe as possible in order to safeguard the health of women who cannot avoid abortion. The most advanced development in abortion technology is medical abortion. At present, the best available method is the combination of an antiprogesterone (RU-486) and a low dose of prostaglandin, either in an injection (sulprostone) or in a vaginal pessary (gemeprost). The currently employed treatment schedules are still not optimal. The treatment lasts for at least 48 or 72 hours and close follow-up is needed to assess whether the treatment has been successful or not. The side-effects, however, are negligible, and the medical method is free from the complications of the surgical methods and those of anaesthesia. The high efficacy (95% complete abortion rate at a gestational age up to eight weeks) restricts the risk of surgery and anaesthesia to the 5% failures. Further research is required to develop a more appropriate treatment schedule, preferably a single-shot treatment. At the same time, the prevention of misuse of the medical methods must be guaranteed to achieve a better acceptance of these safe abortion methods by society. For the time being, medical supervision and follow-up seems to be mandatory, and a 'do-it-yourself' home method providing complete privacy must be regarded as unsafe and medically unacceptable. PMID- 2225609 TI - 1990 proceedings of the Knee Society. A symposium. PMID- 2225610 TI - Scintigraphic determination of patellar viability after excision of infrapatellar fat pad and/or lateral retinacular release in total knee arthroplasty. AB - A prospective study ascertained the effect of lateral retinacular release and/or excision of the infrapatellar fat pad on patellar vascularity after total knee arthroplasty. Fifty patients (70 knees) had postoperative technetium bone scans, which revealed a higher incidence of vascular compromise of the patella after lateral release than without lateral release. Excision of the infrapatellar fat pad, commonly performed to enhance exposure and simplify access to the proximal tibia, did not compromise patellar vascularity. PMID- 2225611 TI - Treatment of juxtaarticular nonunion fractures at the knee with long-stem total knee arthroplasty. AB - A retrospective study of ten patients with juxtaarticular nonunions at the knee treated with long stem total knee arthroplasty was performed. The average age of the patients was 76 years old, with an average follow-up of 36 months. The nonunions were present for an average of 36 months. There were six patients in the series with prior total knee arthroplasty. Clinical union was achieved in all ten patients. All patients improved their ambulatory status. Range of motion improved from an average preoperative range of 40 degrees to an average postoperative range of 85 degrees. Complications occurred in three of ten patients, with one being a postoperative infection. Surgical techniques are described to aid in treatment of difficult juxtaarticular nonunion fragments. PMID- 2225612 TI - Patellar resurfacing in total knee arthroplasty. AB - Technical errors in patellar resurfacing at the time of total knee arthroplasty (TKA) are responsible for many of the complications that affect the patellofemoral joint. Instability, patellar fracture, and wear of metal-backed patellar implants are significantly affected by errors of patellar resurfacing. A review of 50 TKAs using a condylar prosthesis and a standardized technique for patellar resurfacing was performed to evaluate the accuracy of the technique. The patients were evaluated at a mean of 2.5 years (range, two to five years) after surgery. The Hospital for Special Surgery Knee Score improved from a preoperative mean of 56 to 92 at the last evaluation. The Hospital for Special Surgery Knee Scores were excellent in 92% and good in 8%. The Knee Society Knee Score improved from a preoperative mean of 28 for pain and 49 for function to a last evaluation mean of 96 for pain and 85 for function. None of the patients had symptoms referable to the patellofemoral joint. There were no patellar fractures, dislocations, or instances of implant loosening of the patella. Roentgenograms revealed nine asymmetrically resurfaced patellae and five tilted patellae. There were no patellar subluxations. Patellar thickness was maintained at the preoperative level of 21 mm. Joint-line height was elevated 1 mm. The patellar height was decreased 2 mm from the preoperative height. Using a standard technique, satisfactory clinical results can be achieved, but minor errors in resurfacing and alignment will still occur. PMID- 2225613 TI - Radionuclide imaging of asymptomatic versus symptomatic total knee arthroplasties. AB - Ninety-eight total knee prostheses were evaluated by roentgenograms and bone scans. Fifty-three were asymptomatic, and 45 were symptomatic. Thirteen prostheses required revision surgery. At a mean of 54 months, asymptomatic knee replacements generally showed only mild uptake in one or more zones. Only one knee had uptake equal to surrounding bone. However, symptomatic knee replacements showed significantly greater uptake in the patella, femur, and medial and lateral tibial plateau regions (Mann-Whitney two-sample rank test). Bone scans in the symptomatic group were obtained at a mean of 44 months. Excluding those patients who had revision surgery, the differences remained significant. Furthermore, symptomatic knee replacements with normal roentgenograms also had significantly greater uptake. Radiolucent lines were noted in 30% of asymptomatic patients, whereas 29% of symptomatic knees had radiolucencies. Radiolucencies were not generally associated with significantly greater uptake. Lateral release had no effect on the patellar score. PMID- 2225614 TI - Cemented total knee arthroplasty for gonarthrosis in patients 55 years old or younger. AB - The results of 68 cemented total knee arthroplasties (TKAs) in 50 patients with gonarthrosis who were 55 years old or younger at the time of surgery were reviewed. These patients were operated on between 1979 and 1987 and were followed for an average of 6.2 years. The average age of the patients was 50 years. Patients were evaluated by the Hospital for Special Surgery knee score. The average preoperative score was 53, and the average follow-up score was 90. Overall, 55 TKAs were rated as excellent and 13 as good. Using the knee rating score advocated by the Knee Society, the average postoperative score was 92 for pain and 84 for function. There were four successful reoperations for patellar component loosening, all in metal-backed patellae. The femoral and tibial components in these patients were intact, and at the follow-up period, two knees were rated as excellent and two as good. Detailed roentgenographic evaluation demonstrated that 20% of tibial components had radiolucencies in at least one zone on the anteroposterior roentgenogram and in 11% on the lateral roentgenogram. Femoral radiolucencies occurred in only 2% of knees. Patellar radiolucencies in one or more zones occurred in 20% of knees that had not had patellar revision. No complete or progressive radiolucencies at the bone-cement interface were noted for any component, and no components were considered to be roentgenographically loose. Cemented TKAs can achieve excellent long-term results in patients younger than 55 years old with gonarthrosis of the knee. These results compare with those obtained in published reports on older age groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225615 TI - Total knee arthroplasty in diabetes mellitus. AB - A retrospective study was done of 59 total knee arthroplasties (TKAs) in 40 patients diagnosed with diabetes mellitus. The overall infection rate was 7%, with an overall revision rate of 10% and an average follow-up period of 4.3 years. Wound complications were present in 12% of the TKAs. The rate of deep joint infections in diabetic patients was statistically higher than the reported incidence of sepsis in nondiabetic patients. Therefore, maximum precautions should be taken for diabetic patients having TKA to minimize both wound complications and joint sepsis. PMID- 2225616 TI - Bone loss in the distal anterior femur after total knee arthroplasty. AB - Bone loss in the distal anterior femur in asymptomatic total knee arthroplasty (TKA) patients has been noted roentgenographically and during revision surgery. A retrospective roentgenographic review of 147 TKA cases was carried out to document bone loss. The influence that the mode of fixation (porous coated and cemented) and the implant design have on bone loss was examined. The time of onset and the progression of bone loss were studied. Bone loss occurred in the distal anterior femur in the majority of cases reviewed (68%). The prevalence of bone loss was independent of the mode of fixation and the implant design. By qualitative observation, roentgenographically detectable bone loss occurred within the first postoperative year and did not progress further. Previously three-dimensional finite element analysis demonstrated that the replacement of the bearing surface of the femur with a stiff metallic implant reduces the stress in the distal anterior femur by at least one order of magnitude. It is therefore speculated that the observed bone loss results from stress shielding. The apparent lack of progression may reflect the development of a new remodeling equilibrium under the altered stress conditions. The bone loss in the distal anterior femur described has not been implicated as a source of failure. However, since the bone strength in the femoral region is compromised as it becomes osteopenic, bone failure may occur with longer periods of cyclic loading. Furthermore, as a result of bone loss, revision arthroplasty may be more difficult. PMID- 2225617 TI - Massive allografts in salvage revisions of failed total knee arthroplasties. AB - Ten patients with failed total knee arthroplasties and severe bone loss were treated with massive whole distal femur and proximal tibial allografts in combination with prosthetic implants. Fourteen allografts were inserted either as invaginated or segmental grafts and were rigidly fixed to the host bone. Clinically and roentgenographically, 12 of 14 grafts (86%) seemed to have united to the host bone. The average range of motion was 92 degrees. Five patients developed complications; two of these involved the allograft (nonunion and fracture) and two were caused by inadequate healing at the ligament-allograft junction. One patient had a late infection. With careful planning and improved surgical techniques, these complications can be avoided. The massive allograft prosthesis composite techniques is a viable reconstructive alternative worthy of further clinical trials. PMID- 2225618 TI - Reconstruction of patellar tendon rupture after total knee arthroplasty with an extensor mechanism allograft. AB - Although patellar tendon rupture after total knee arthroplasty (TKA) is a rare complication, the consistently poor outcome of conventional tendon repair has convinced some to abandon such reconstruction in favor of a prospective protocol using an allograft distal extensor mechanism. The graft consists of a quadriceps tendon, a patella with a cemented prosthesis, a patellar tendon, and a tibial tubercle. Since December 1985, 13 knees in 12 patients were reconstructed using this method. Ten knees were followed for six to 51 months; five of these knees were followed for more than 24 months. Knee extension power and improved function were ultimately attained in all cases, although minimal extensor lags were present in three cases. Preoperative motion returned in all but one knee. Healing of the allograft to the host tissue was attained primarily at all of the tibial junctions. Two graft complications occurred, both in the first three months after surgery: one quadriceps junction treated by resuture failed at the one-month mark, and the other graft had to be revised for extensor weakness from rupture of the graft at the patella-patellar tendon junction, which was attributed to surgical damage to the tendon. After completion of healing to the host and rehabilitation of the knee joint, no grafts in the series failed during the course of normal daily activities. One patient fractured the allograft patella in a severe fall. The long-term durability of this construct needs to be studied further. PMID- 2225619 TI - Long-term survivorship analysis of cruciate-sparing versus cruciate-sacrificing knee prostheses using meniscal bearings. AB - A comprehensive, interchangeable, low-contact-stress, mobile-bearing knee prosthesis system was developed and used over a 12-year period with both cemented and cementless fixation. Individual components of the system included a bicruciate-retaining meniscal bearing, a posterior cruciate-retaining meniscal bearing, and a cruciate-sacrificing, rotating-platform tibial component mated to the same femoral and rotating patellar components. Survivorship analysis of each implant type was performed to identify specific failure modes and trends for long term survival of the implants in a wide variety of primary knee arthroplasties. Clinically, there were 46 prostheses of the bicruciate type followed for up to 12 years, 57 prostheses of the posterior-cruciate type followed for up to six years, and 108 prostheses of the rotating-platform type followed for up to ten years. All knees in this study had rotating-bearing patellar prostheses. Cumulative survivorship analysis using an end point of implant revision or a poor knee score revealed a small early failure rate of each implant in the first three years, associated with technical positioning or undersizing errors. This study indicates a predictable long-term survival of both cruciate-retaining and cruciate sacrificing mobile-bearing knee prostheses as well as rotating-bearing patellar prostheses when used in primary knee arthroplasties that minimized technical errors of insertion. PMID- 2225620 TI - A sequential three-step lateral release for correcting fixed valgus knee deformities during total knee arthroplasty. AB - An approach to mild, moderate, and severe fixed valgus deformities of the knee is described. The sequential approach to soft-tissue releases in the fixed valgus knee allows the surgeon to regain a neutral alignment in valgus deformities of up to 90 degrees. An additional benefit of the approach is spontaneous correction of fixed external tibial rotation deformities. Using this approach, early and late stability allows the use of unconstrained knee implants, including those with mobile-bearing elements. PMID- 2225622 TI - Anaphylactic shock associated with chymopapain skin test. A case report and review of the literature. AB - The allergic response to chymopapain intradiscal therapy has been well documented. The most serious of these reactions is anaphylactic shock, which may result in death. Various screening methods, including skin tests, have been proposed to identify susceptible patients. Anaphylactic shock occurred in a 40 year-old woman from application of the screening skin test. Appropriate therapeutic intervention should be readily accessible when this test is performed. PMID- 2225621 TI - Magnetic resonance imaging and computer tomography of acute spinal cord trauma. AB - Spinal cord lesions are not detectable on roentgenograms and computed tomography (CT) scans. Magnetic resonance images (MRIs) are able to make soft-tissue lesions visible. Interpretations of MRIs, CT scans, and roentgenograms were compared in 25 patients and three postmortem specimens with spinal cord injuries. In 14 patients and one specimen with normal roentgenograms and CT scans, the MRI demonstrated ten soft-tissue injuries as minimal displacement of the vertebral bodies or as a high signal intensity in the disc space, indicating a hematoma. Seven of the ten patients demonstrating soft-tissue injuries also had an intramedullary lesion, while in five of the 15 patients with normal CT scans, only a medullary lesion was present on MRI. In 11 patients and two postmortem specimens, fractures were seen on roentgenograms and CT scans. In these patients, the CT was superior to the MRI in detecting small bony fragments, but the medullary lesions were visible only on the MRIs. An intramedullary low signal intensity corresponded to macroscopically visible hemorrhages in the three postmortem specimens. The MRI provided important information in patients with neurologic deficits. No obvious pathologic changes were evident on the roentgenograms and CT scans. The MRI also demonstrated intramedullary and extramedullary soft-tissue lesions and was useful in establishing a diagnosis and in choosing appropriate therapy. CT, on the other hand, was superior in detecting small bony fragments and fracture lines. PMID- 2225623 TI - HTLV-I viral-associated myelopathy after blood transfusion in a multiple trauma patient. AB - This may be the first documented case in the United States and in the orthopedic literature of transfusion-transmitted human T-cell leukemia virus Type I (HTLV-I) associated myelopathy (HAM). Progressive myelopathy occurred in a 58-year-old white man with serologic and molecular evidence of HTLV-I infection after multiple trauma and subsequent transfusion with multiple units of banked blood products. Symptoms of myelopathy occurred 15 months after the transfusions. Myelopathy from HTLV-I infection simulates a disorder of orthopedic interest. Physicians should be aware of the symptoms of HAM and unexplained myelopathy. PMID- 2225624 TI - Anterior acromioplasty for treatment of the shoulder impingement syndrome. AB - Between 1975 and 1979, anterior acromioplasty was performed in 65 patients with 66 involved shoulders. The procedure appears to be safe and reasonably effective. Of the 65 patients in this study, 50 had chronic tendon inflammation with fibrosis, and 16 also had a small supraspinatus tendon tear. These 16 had rotator cuff repairs. Twenty-six patients were also treated with distal clavicle excision, and seven had tenodesis of the long head of the biceps brachii. The average age of the patients was 50 years (range, 23-75 years). All patients were followed for an average of eight years (range, three to 13 years). At final evaluation, no or slight pain was present in 77% of the shoulders: 39 of 50 without tendon tearing and 12 of 16 with tendon tearing and repair. Active shoulder abduction averaged 167 degrees. Ninety-two percent returned to employment, including 18% with some job modification. Eighty-six percent returned to recreational athletics, 20% with some modification of activities. Seven patients had additional surgical treatment. The progression of rotator cuff disease is not always prevented, but the need for subsequent shoulder treatment generally decreases. PMID- 2225625 TI - Humeral head retroversion in patients with unstable humeroscapular joints. AB - Humeral head retroversion and shoulder rotation in both the frontal and scapular plane were studied in 34 patients with anterior glenohumeral instability. Twenty two patients had traumatic anterior shoulder dislocations and another 12 patients had nontraumatic dislocations with generalized joint laxity. Patients with traumatic recurrent dislocations had a smaller than normal retroversion angle in the unstable shoulder. The angles were 26 degrees on the dominant side and 23 degrees on the nondominant side compared with 33 degrees and 29 degrees, respectively, in normal shoulders. The stable contralateral shoulder joint was clinically and roentgenographically similar to the normal shoulder. The patients with nontraumatic dislocations had increased rotation and smaller retroversion angles, irrespective of stability in the shoulder joint. The retroversion angles were 18 degrees for unstable shoulders on the dominant side and 15 degrees on the nondominant side. The retroversion angle of the stable contralateral joint in these patients was less in five of eight shoulders. PMID- 2225626 TI - Chondrosarcoma complicating total hip arthroplasty in Maffucci's syndrome. AB - A 70-year-old woman who was followed for 60 years for Maffucci's syndrome required a total hip arthroplasty (THA) of the right hip for degenerative arthritis. This did not relieve pain. Three years later, chondrosarcoma of the femur developed around the femoral component and was fatal. The roentgenographic changes after the THA were incorrectly interpreted as being caused by infection. PMID- 2225627 TI - Total hip arthroplasties in patients younger than 45 years. A nine- to ten-year follow-up study. AB - Eighty-one cemented total hip arthroplasties in patients younger than 45 years were reviewed with an average 9.2-year follow-up interval. The results were compared with the same group previously reported at an average follow-up time of 4.5 years. Clinically satisfactory results were 58% compared with 78% at 4.5 years. The revision rate almost tripled to 33%. Impending failure was present in 56% of those hips not yet revised. In the first study, technique was a primary determinant of success. In this report there was no influence of technique on the incidence of revision. Age did not influence revision rates either, with 35% in patients younger than 30 years and 32% in patients aged 30-45 years. Patients younger than 30 years had fewer satisfactory clinical results and a higher rate of impending failure. As in the first study, the best results were obtained in patients with inflammatory collagen disease aged from 30 to 45 years. PMID- 2225628 TI - Femoral neck fractures in patients receiving long-term dialysis. AB - The morbidity and mortality of 11 femoral neck fractures were analyzed to compare operative and conservative management of femoral neck fractures in dialysis patients. All fractures occurred in older men with severe cardiac, pulmonary, gastro-intestinal, and neurologic conditions and with advanced renal osteodystrophy. Six of the seven operated patients survived the surgery and achieved varying degrees of ambulation. Stability of the operated hip was excellent in each case. Post-operative complications included transient confusional state related to narcotics, pneumonia, decubitus ulcers, and severe hypoalbuminemia. All four patients who were managed conservatively died from complications of the fracture. Progressive deterioration was noted in each nonoperated patient, with confusion caused by narcotics and analgesics, pneumonia, hepatic coma, decubitus ulcers, severe depression, and severe hypoalbuminemia. Therefore, operative management was superior to conservative management for femoral neck fractures of patients receiving chronic dialysis with multiple medical problems and advanced renal osteodystrophy. Narcotics must be used with great caution, and efforts should be directed toward prevention of malnutrition and decubitus ulcers. PMID- 2225630 TI - Complications associated with limb salvage for extremity sarcomas and their management. AB - A retrospective clinical review of 100 consecutive patients with extremity sarcomas managed by limb salvage operations was performed to evaluate local tumor control and morbidity. The mean follow-up period was 45.1 months. Overall survival was 86%. There were local recurrences in 3% of patients, and 26 complications in 22 patients. Wound necrosis was the most frequent complication. Failure of allogeneic bone graft operations occurred in 25 patients. Most of the complications were salvageable without loss of limb. Limb salvage is an acceptable surgical treatment of extremity sarcomas based on adequate local control and minimal morbidity. PMID- 2225629 TI - Mechanical measures in the prophylaxis of postoperative thromboembolism in total knee arthroplasty. AB - Total knee arthroplasty patients are at high risk for deep venous thrombosis and pulmonary embolism. Prophylaxis against deep venous thrombosis and pulmonary embolism in these patients seems mandatory. Pharmacologic agents such as dextran 40, aspirin, and warfarin are effective but may be associated with significant complications such as drug reaction, bleeding, hematoma, and hemarthrosis. Heparin was not effective and was associated with significant bleeding complications. Mechanical methods such as continuous passive motion and sequential pneumatic compression stockings were without complications and seemed equal to or more effective than pharmacologic agents. Adding warfarin to mechanical methods did not seem to augment the antithromboembolic effect of the mechanical methods. PMID- 2225631 TI - Giant-cell reparative granuloma of the hand and foot bones. AB - Giant-cell reparative granuloma (GCRG) is an uncommon benign reactive intraosseous lesion. It occurs in the skull, jaw, hand, foot, and facial bones and rarely in other skeletal sites. It is a solitary, lytic, expanded lesion and infrequently may extend into the surrounding soft tissue. Histologically, it is composed of fibrous stroma with spindle-shaped fibroblasts, multinucleated giant cells, and inflammatory mononuclear cells. Areas of hemorrhage are uniformly present. It may be difficult to distinguish this entity from an aneurysmal bone cyst, giant-cell tumor, or brown tumor of hyperparathyroidism because of roentgenographic and histologic similarities. Accurate diagnosis is essential for appropriate treatment; serum calcium, phosphorus, and parathyroid hormone levels should be measured. Curettage and bone graft are effective treatments for both primary lesions and recurrences. Second recurrences are rare. PMID- 2225632 TI - Leiomyoma of a digital artery. AB - Benign, soft-tissue masses of the hand are common. A vascular leiomyoma is an unusual tumor of smooth-muscle origin. In a 62-year-old man, the tumor arose from within a digital artery. Persistent symptoms prompted an excisional biopsy, requiring resection of a portion of the artery. Adequate collateral circulation preempted the need for a vascular graft. Vascular repair or grafting may be necessary if collateral circulation is not adequate. PMID- 2225633 TI - Immune responses to allogeneic and xenogeneic implants of collagen and collagen derivatives. AB - Whereas xenogeneic collagen has provided a safe and effective biomaterial for numerous medical applications, there are few instances in which data permit the correlation of the immunologic profile of well-defined devices with their clinical sequelae. A major exception is the use of injectable bovine dermal collagen for soft-tissue contour correction. The low incidence of hypersensitivity has been studied in the context of clinical efficacy and safety with several devices. The findings indicate that such immunity usually results in the manifestation of local symptoms of dermal inflammation at sites of treatment that resolve as the implant is resorbed by the host. In contrast, more immunogenic hemostatic agents may elicit a more frequent or vigorous immune response that is not clinically visible or relevant in that application. Recent experiences with collagen-based devices for the repair and regeneration of bone have also demonstrated that the presence of immunity to their collagenous or non collagenous components does not necessarily predict adverse clinical sequelae. Indeed, numerous specific data indicate that this immunity can exist as an epiphenomenon with no effect on osteogenesis. To get a true composite picture of biocompatibility, significant steps must be taken to characterize biomaterials properly and to ensure that immunologic, clinical, histologic, and other pertinent laboratory data are viewed in relation to one another and not in isolation. PMID- 2225634 TI - Primary inflammatory reaction in synovial fluid and tissue in rabbit immobilization osteoarthritis. AB - The kinetics and composition of the primary cellular inflammatory process were studied in the synovial fluid (SF) and synovial tissue (ST) compartments of a rabbit knee immobilization osteoarthritis model. Immobilization induced rapid migration of neutrophils (59% +/- 26% of all cells) into SF in three days, which was accompanied by nonspecific esterase-positive monocytes (71% +/- 8% of all mononuclear cells). This finding suggests that non-specific inflammation mediated by phagocytic leukocytes predominates the cellular response in the SF compartment. In contrast, morphometric analysis of ST proper showed an inflammatory mononuclear cell response, the intensity of which diminished over time during the study period from Day 3 (416 +/- 59 cells per 0.049 mm2 ST tissue) through Day 10 (305 +/- 32 cells) to Day 35 (174 +/- 36 cells). A dotlike T-pattern alpha-naphthyl acetate esterase (ANAE) was found in the T-cell dependent areas of secondary lymphatic tissue in the spleen, enabling immunocytologic ANAE marker studies. The ST response in situ was predominated by tissue macrophage, though infiltrates rich in T lymphocytes were present in the immediate sublining stroma. There was a significant correlation between the intensity of the SF cell response (total recovery) and the percentage of neutrophils, but there was no correlation between the intensity of the ST response and the proportion of T lymphocytes. These T-cell accumulations together with the local proliferation of fibroblastlike lining cells and stromal fibroblasts suggest that the primary inflammatory cell response is not caused by either wear and tear or mechanically by cartilage fragments. PMID- 2225635 TI - Long-term morphology of spastic or flaccid muscles in spinal cord-transected rabbits. AB - Despite difficulty in long-term maintenance of spinalized rabbits, muscular pathologic changes in chronic spinalized rabbits could be observed for a period of four weeks. Rabbits were prepared by spinal cord transection at T10 (spastic paralysis) or by spinal cord removal below L7 (flaccid paralysis). Spastic preparations showed hind-limb spasticity and reflex incontinence one to two days after operation. Hypertrophic fibers began to appear in spastic muscles after two weeks. This hypertrophy, thought to be caused by phasic repetitive contraction, was verified by electron microscopy to be different from normal exercise hypertrophy. Flaccid preparations maintained hind-limb flaccidity and overflow incontinence. In flaccid muscle, marked muscle fiber necrosis indicated rapid atrophy. Spinal deformity and joint contracture inactivate spinalized rabbits, and cause pressure sores. However, feeding assistance and avoidance of complications make long-term maintenance possible. PMID- 2225636 TI - A double-blind study on the effects of a capacitively coupled electrical field on bone ingrowth into porous-surfaced canine total hip prostheses. AB - The effect of a capacitively coupled electrical field on bone ingrowth into titanium fiber mesh porous-surfaced canine total hip arthroplasties (THAs) was investigated in a double-blind experiment. The electrical field was induced by an external source delivering a 60-kHz 5-6-V peak-to-peak sinusoid voltage through skin electrodes. No significant increase in the ingrowth of bone into the porous coating occurred at the end of six weeks of electrical stimulation. The amount of bone that grew into the porous surface, the areal density of bone within the available pore space, and the extent of the prosthesis surface area with bone ingrowth or apposition were not significantly different in the control and stimulated groups. This particular form of electrical stimulation does not improve bone ingrowth into porous-surfaced canine THAs by six weeks. PMID- 2225637 TI - An operation for displaced semilunar cartilage. 1885. PMID- 2225638 TI - Important modality available in the diagnostic armamentarium of septic arthritis of the hip is ultrasonography. PMID- 2225639 TI - High tibial osteotomy (HTO) is an effective procedure for medial and patellofemoral disease. PMID- 2225641 TI - The effect of femoral component position on patellar tracking after total knee arthroplasty. AB - In a laboratory study, seven fresh anatomic knee specimens were evaluated to define the three-dimensional motions of the patella before and after total knee arthroplasty (TKA) with the AMK knee. The patella was displaced medially by an average of 4 mm and tilted medially by an average of 4 degrees after standard TKA. Medial translation or internal rotation of the femoral component further displaced and tilted the patella medially, but lateral translation or external rotation of the femoral component produced less predictable changes in patellar tracking. The patterns of patellar tracking after external rotation of the femoral component came closer to reproducing those of the intact knee than any other femoral component position. The high lateral ridge on the femoral component effectively prevents patellar dislocation but may produce abnormally high stresses on the patellar implant, especially if the implant is medially displaced or internally rotated. This could lead to accelerated wear or loosening of the patellar component. PMID- 2225640 TI - Comparison of patellar resurfacing versus nonresurfacing in bilateral total knee arthroplasty. AB - Twenty-five patients who received bilateral total knee prostheses were studied to evaluate the advantages and disadvantages of patellar resurfacing. Only patients with advanced patellofemoral disease were included in the study. In all patients, patellar resurfacing had been done in the right knee but not in the left knee. The DePuy porous-coated implant was used in all cases. Subjective criteria were compared with objective criteria, which included range of motion, knee flexion and extension, and roentgenographic evaluation. The findings in this study suggest that patellar resurfacing can offer the patient a superior knee with regard to pain relief and strength. PMID- 2225642 TI - The use of metal-backed patellar prostheses in total knee arthroplasty. AB - Metal backing of polyethylene prosthesis components decreases deformity of the overlying polyethylene and enhances fixation to the underlying bone. Previous metal-backed patellar designs have often failed, primarily because of implant design and implantation technique. In 451 total knee arthroplasties using metal backed patellar prostheses, there were no implant failures. The implants were dome shaped and did not have a metal endoskeleton. The component was inset into the patellar bone so that the base plate was below the superficial surface of the bone. These factors maximized polyethylene thickness and prevented wearing through to the metal base plate. The advantage of metal backing is that it strengthens the component and allows for possible biologic ingrowth. In this series, the combination of implant design and implantation technique may have eliminated serious problems seen with other metal-backed patellar implants. PMID- 2225643 TI - The inwardly pointing knee. An unrecognized problem of external rotational malalignment. AB - Twelve patients with inwardly pointing knees had chronic knee pain and disability suggestive of patellofemoral subluxation. None had responded well to conservative measures or surgical correction at the level of the soft tissues. Their pattern of limb alignment was studied roentgenographically and was found to differ significantly from the control group of 49 healthy young adults. The deformities primarily related to the tibia were external tibial torsion, excess varus angulation of the tibial plateau, and varus knees. Angulation of the femoral condyles was normal and femoral anteversion did not appear to contribute significantly to the deformity. Surgery in seven cases (nine knees) was by derotation valgus Maquet osteotomy of the tibia and lateral release realignment of the patellae. Outcome assessments after a three-year follow-up period (five knees) were excellent. Early results on the remaining cases were satisfactory. PMID- 2225644 TI - Tibial tubercle osteotomy for exposure of the difficult total knee arthroplasty. AB - Tibial tubercle osteotomy provides a safe and reliable means of extensile exposure of the knee. A technique was developed using a long osteoperiosteal segment including the tibial tubercle and upper tibial crest leaving lateral muscular attachments intact to this bone fragment. The bone fragment was reattached to its bed with two cobalt-chromium wires passed through the fragment and through the medial tibial cortex. The procedure was used in 71 knees to expose the joint for total knee arthroplasty, and the follow-up period was one to five years. All healed uneventfully, and no significant complications occurred. Mean postoperative flexion was 97 degrees. No extension lag occurred, and mean flexion contracture was 2.5 degrees. Excellent exposure can be achieved by means of a viable bone flap below the knee. Early rehabilitation and weight bearing can be done with low potential for complications. PMID- 2225645 TI - Late recurrence of varus deformity after proximal tibial osteotomy. AB - One hundred thirteen knees with medial gonarthrosis in 95 patients were treated by valgus-producing proximal tibial osteotomy and followed clinically and roentgenographically for a minimum of five years (mean, 6.3 years). Sixty-four knees (57%) were pain free or had only mild discomfort when walking. The standing femorotibial angle decreased from a postoperative average of 9.3 degrees valgus to 7.8 degrees valgus at the final follow-up examination. The tendency for varus recurrence greater than 5 degrees and for medial- or lateral-compartment arthritic progression was evaluated using the Kaplan-Meier survival method. Varus recurred in 18%, lateral-compartment arthritic progression in 60%, and medial compartment arthritic progression in 83% by nine years after surgery. The probability of arthritic progression is much higher than the probability of significant varus recurrence in long-term roentgenographic follow-up studies of patients with valgus-producing proximal tibial osteotomies. PMID- 2225646 TI - Total knee arthroplasty fixation. Comparison of the early results of paired cemented versus uncemented porous coated anatomic knee prostheses. AB - The results of 18 matched pairs of Porous Coated Anatomic knee prostheses were studied to compare the early clinical and functional performance of cemented versus uncemented fixation with an average five-year follow-up period for both. The knee score improved from a preoperative average of 35 points to a postoperative average of 90 points in the cemented group, and from 38 points to 93 points in the uncemented group. In particular, the individual pain scores and the range-of-motion values were well matched at the three-, six-, and 12-month follow-up visits and showed a steady improvement. Subjectively, all patients were pleased with the results of surgery; one-third preferred the cemented side, one third preferred the uncemented side, and one-third found no difference in the performance of either knee. The clinical and functional performance of knee prostheses in patients who had one cemented knee and one uncemented knee were comparable and possibly unrelated to the type of fixation method. PMID- 2225647 TI - Cemented and ingrowth fixation of the Miller-Galante prosthesis. Clinical and roentgenographic comparison after three- to six-year follow-up studies. AB - One hundred thirty-nine cemented and 132 cementless Miller-Galante total knee prostheses were followed between three and six years (average, 43-44 months). The fixation technique was based on patient age, bone quality, and ability to delay full-weight bearing. Clinical follow-up studies were possible on 116 cemented knees. Fifteen knees were lost because of death before the three-year follow-up study, and eight knees required component removal. One hundred twenty-three cementless knees were available for clinical follow-up studies; there were three deaths, and six failures required component removal. No cemented failure was due to fixation, and three cementless failures were due to lack of tibial ingrowth in two and pain of undetermined etiology in one. Preoperative knee scores were slightly significant with cemented knees averaging 48 points and cementless knees averaging 52 points. A similar significant difference was maintained at the final follow-up study. No significant differences were noted for pain, limp, or support scores. Average range of motion was similar in the two groups. Radiolucent lines about the femoral component were rare. Cementless tibial radiolucencies were partial in up to 20% of examined zones, and complete tibial tray radiolucency was seen in only three patients. No correlation between radiolucency and knee scores was seen. PMID- 2225648 TI - Two- to four-year results of posterior cruciate-sparing condylar total knee arthroplasty with an uncemented femoral component. AB - One hundred fourteen hybrid Press-Fit Condylar total knee arthroplasties (TKAs) were reviewed an average of 2.8 years after surgery to determine if this method of implantation provided satisfactory results compared with conventional cemented TKAs. Ninety-three percent of the knees had good or excellent results, and 94% of the knees had at most only mild or occasional pain. One knee with a metal-backed patella was revised for mechanical failure of the patellar button. Roentgenographic analysis of the femoral component interface showed that 30% of knees had a radiolucent line in at least one zone. However, none of the lines was wider than 1 mm, and none was about the central stem. There were no signs of loosening about any of the components. It was concluded that hybrid TKA provides a good and predictable result that is comparable to cemented TKA. PMID- 2225649 TI - Review of the all-polyethylene tibial component in total knee arthroplasty. A minimum seven-year follow-up period. AB - A retrospective analysis of 144 total knee arthroplasties was performed between 1975 and 1981 with a minimum follow-up period of seven years. A posterior cruciate condylar prosthesis was used in each procedure. Patients were followed clinically and roentgenographically, and a set of statistical variables was established based on elevation in joint line, tibial component angular alignment, overall limb alignment, and position of the tibial component on anteroposterior and lateral roentgenograms. Review of the study group found that the Hospital for Special Surgery knee scores improved from a preoperative score of 55 to a postoperative score of 88, with 94.5% having good or excellent results. The mean postoperative range of motion was 106 degrees with a mean extension of -0.3 degrees. Radiolucencies developed in 41% of the knees with 5% of the knees having progressive radiolucencies. Eight knees were considered failures based on clinical and roentgenographic evaluations. Factors found to significantly affect the formation of radiolucent lines included a shift of the tibial component medially by greater than 4 mm, a varus tilt of the tibial component greater than 2 degrees, and the diagnosis of rheumatoid arthritis. The only variable associated with aseptic loosening was an elevation of the joint line by greater than 8 mm. PMID- 2225650 TI - An all-polyethylene cementless tibial component. A five- to nine-year follow-up study. AB - An all-polyethylene cementless tibial component was used in 221 total knee arthroplasties. With one exception, failures did not occur before three years. Failure was characterized by medial subsidence of the tibial component. There was abrasion of the polyethylene on the undersurface of all components that failed. Survivorship was seven to nine years (87.1%). This study demonstrated that a flexible cementless component can function well when used with any type of bone. However, abrasion of the polyethylene that occurs from shearing forces is a concern. Polyethylene components need adequate provisions to prevent shearing or need surface treatment to prevent abrasion. PMID- 2225651 TI - A correlative study of the geometry and anatomy of the distal femur. AB - Sixteen knees were examined roentgenographically in the lateral plane. Ten knees were examined from autopsy subjects. The distal articular femur may be represented by three circular surfaces: (1) the floor of the patellar groove (articulating with the patella from 10 degrees to 100 degrees), (2) the posterior femoral condyles (articulating with the tibia from 10 degrees to 150 degrees), and (3) the distal condyles (articulating with the tibia from 0 degrees to 10 degrees). The radii of these surfaces, their angular arcs, and the distances between their centers varied with the size of the femur but fell within a narrow range. The radii of the patellar groove and the posterior femoral condyles averaged 24 mm and 21 mm, and the average angle subtended by these arcs was 90 degrees and 140 degrees, respectively. The average distance between the centers of these two circles was 20 mm. The femoral attachment of the synovial and patellar retinacular reflections was found in the area of the center of the patellar groove circle. The femoral attachments of the medial collateral and posterior cruciate ligaments and of the lateral collateral and anterior cruciate ligaments were found to be in the area of the center of the circle of the medial and lateral posterior femoral condylar circles, respectively. PMID- 2225652 TI - [Short-latency somatosensory evoked potentials and magnetic resonance imaging in the medial medullary syndrome]. AB - A 57-year-old woman was admitted to Kakeyu Hospital complaining of paresis of the left upper and lower extremities which suddenly developed three years ago. Neurological examination revealed spastic paresis of the left upper and lower limbs without facial and lingual paresis. The reflexes were abnormally brisk on both sides but they were more remarkable on the left side, which also showed Babinski's sign. Sensitivity to light touch and vibration was moderately decreased and sensitivity to pinprick and joint position was minimally decreased in the left upper and lower extremities. No cerebellar sign was observed. Needle EMG disclosed large motor units with an amplitude of 4-5 mV and a duration of 8 msec in the light half of the tongue during weak contraction. MRI using a 0.5-T superconducting magnetic resonance unit detected a small, wedge-shaped infarction in the anterior medial portion of the medulla just below the pontomedullary junction. Somatosensory evoked potentials (SEPs) after median nerve stimulation with a non-cephalic reference were recorded. After stimulation of the left side, the scalp-recorded P13 was recognized at the normal latency, but the later components, N16 and N18, were apparently absent. On the other hand, SEPs in another case with thalamic hemorrhage revealed normal N16 potential with absence of N18 on the affected side. From these SEP findings and the reports on SEPs in lesions of the brain stem or thalamus, it was suggested that P13 is abnormal in lower medullary lesions and is preserved in upper medullary lesions, and that N16 is abnormal in brain stem lesions and is preserved or changed a little in thalamic lesions. PMID- 2225653 TI - [An MRI study of hereditary spinocerebellar degenerations]. AB - We evaluated magnetic resonance image (MRI) in 21 cases of hereditary spinocerebellar degenerations (SCD) of autosomal dominant trait. By the discriminant formula based on size of the cerebellar vermis and ventral pons, which was reported in our previous study, the patients were classified into three types. Group 1 included the cases with atrophies in the vermis and pons; OPCA type. Group 2 showed vermian atrophy and less significant atrophy in pons; LCCA type. And Group 3 was no significant atrophies both in vermis and pons. Cases in Group 1 were furthermore divided into two groups according to width of the midbrain tegmentum. Group 1A, with normal midbrain tegmentum, was consisted of five cases. Four cases were diagnosed as Menzel type OPCA. Another case showed various clinical symptoms and relatively mild atrophies for his duration of illness. His family members were classified to Group 3. Seven cases in Group 1B showed reduced midbrain tegmentum. Four cases showed ataxia, spasticity, ocular symptoms, bladder dysfunction and amyotrophy with or without fasciculation, and they seemed to be a special type of SCD mimicking Joseph disease. One case showed bulging eyes, ocular movement palsy and dystonia. However, his sister manifested only ataxia with very mild ocular movement disorder. Their MRI demonstrated severe atrophies in the cerebellum, pons and afferent cerebellar peduncli, and this pedigree was thought to be Menzel type OPCA with various associated disorders. Another case was clinically diagnosed as dentate-rubro-pallido-luysian atrophy. Group 2 was consisted of 6 cases who were clinically diagnosed as Holmes type LCCA. MRI demonstrated medial dominant cerebellar atrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225654 TI - [Biochemical study on different situations of type 2C fiber in rats]. AB - Type 2C fibers from the soleus, gastrocnemius and extensor digitorum longus muscles of the rats were histochemically and biochemically examined in three different conditions; muscles in the neonatal stage, after neonatal denervation and on regenerating process after bupivacaine induced injury. On histochemical examination, neonatal muscles contained 100% of type 2C muscle fibers in all muscles examined, denervated muscles 94% in soleus, 42% in gastrocnemius and 57% in extensor digitorum longus and bupivacaine treated muscles 90%, 61% and 73% of type 2C fibers, respectively. On biochemical analyses, the triglyceride was the smallest and glycogen the largest in amount in all neonatal muscles, triglyceride was the largest and glycogen low in amount in neonatally denervated muscles, both triglyceride and glycogen were low in amount in bupivacaine treated regenerating muscles. And the fatty acid compositions of triglyceride were also different in different type 2C fibers. These results suggested that though histochemical characteristics are the same, significant differences in biochemical properties are present between type 2C fibers of these three conditions in that there are the smallest amount of triglyceride and the largest amount of glycogen in denervated muscles, are both low amount of triglyceride and glycogen in regenerating fibers. PMID- 2225656 TI - [A case of flexion myelopathy presenting juvenile segmental muscular atrophy of upper extremities--a successful treatment by cervical spine immobilization]. AB - A 24-year-old man was well until 1982, when he noticed weakness and atrophy of right arm especially those of biceps muscles. These symptoms did not progress until 1988. In 1988 weakness of left elbow flexion appeared and he was admitted to our hospital. On examination, he had weakness and atrophy of both upper extremities. Fasciculation was noticed in the proximal part of right arm. When his head was bent forward, dysesthesia appeared around radial side of his arm. There were no long tract sign or objective sensory loss. EMG showed neurogenic change over both his upper extremities. In plain cervical roentgenogram there existed abnormal kyphosis of cervical vertebrae. In MRI imaged with his neck flexed, cervical cord was compressed by the posterior surface of 4th cervical vertebral body, which corresponded to the top of cervical kyphosis. Based on these signs and examinations, a diagnosis of flexion myelopathy was made. Spinal immobilization by wiring and bone graft implantation ranging from C2 to C6 was performed to limit the range of anterior nuchal flexion. After this operation, improvement of muscle strength along with the disappearance of dysesthesia on neck flexion was observed. Clinically, this case closely resembles to juvenile type of distal and segmental muscular atrophy of upper extremities (Hirayama type). From our study, pathomechanism of this case seems to be a flexion myelopathy at C4 level. This view is supported also by the good recovery after the operation. This case suggests that nonprogressive atrophy of upper extremities due to flexion myelopathy can be successfully treated by cervical spine immobilization. PMID- 2225655 TI - [Calf impedance plethysmographic evaluation of peripheral sympathetic nerve activity--comparison with microneurographic analysis]. AB - Although the method of impedance plethysmography made it possible to evaluate the vascular resistance of lower extremities, the actual correlation to the sympathetic nerve activity is not known. We performed examinations of microneurography and impedance plethysmography of the lower extremities, in six healthy volunteers, placed on a tilting table. Blood pressure, heart rate, muscle nerve sympathetic activity to calf muscles (microneurography), calf vascular resistance (impedance plethysmography) were simultaneously recorded with increasing angles of the head-up tilting (0, 30, 60 degrees). With the increase of tilting angles, sympathetic nerve activity and the calf vascular resistance significantly increased and these values were statistically correlated to the increase of tilting angles (expressed as sine function). Moreover, a statistically significant positive correlation was observed between the sympathetic nerve activity and vascular resistance. We concluded that the impedance plethysmographic method for measurement of calf vascular resistance is a good indicator for evaluating the peripheral sympathetic nerve activity. PMID- 2225657 TI - [A case of acute mountain sickness with bilateral lesion of pallidum]. AB - The patient was 56-year-old female, who suffered from ataxia and then fell into coma on the next day after she had moved from the sea level to an altitude of 4,200 m. After she was brought to lower altitude, consciousness recovered within several hours. For about 2 days thereafter, disorientation was observed, and she was diagnosed as AMS (acute mountain sickness). Only insomnia continued in chronic stage. The results of X-ray computed tomography (CT) on 25th day after the onset of the disease revealed no abnormal finding except the slightly increasing uptake of contrast material. Symmetrical low density regions were seen in bilateral basal ganglia after one year, and the globus pallidus lesions were confirmed by magnetic resonance imaging. In the past, cerebral edema has been reported in most cases of AMS, and the neurotic symptoms of AMS have been attributed to cerebral edema, while the essential condition of this disease is not yet elucidated. In the present case, the globus pallidus lesions could be identified through the following-up of the central nervous system by X-ray CT and MRI as the first attempt for the case of AMS. There has been no report of globus pallidus lesions in the cases of AMS. Whereas low oxygen partial pressure is the primary cause of AMS, and it is highly probable that the disorders in globus pallidus as reported in the cases of carbon monoxide poisoning, anesthetic accident, etc. are related to the occurrence of AMS. PMID- 2225658 TI - [A case of idiopathic hypoparathyroidism with extrapyramidal signs and insulin dependent diabetes mellitus]. AB - A case of a 29-year-old woman with idiopathic hypoparathyroidism was reported. There were neither endocrine nor neurological disorders among her family, except for her mother's hearing loss. She had been suffering from insulin-dependent diabetes mellitus since 21 years of age, and was noticed to be hard of hearing for several years, but never been examined. At the age of 27, choreic movement on her left upper limb and gait disturbance appeared. A year before admission, gait disturbance gradually developed and she could not walk any more. On admission, her height was 137.2 cm and her weight 36.5 kg. She had a round face, uneven teeth and borderline metacarpal sign on her right hand. On neurological examination, Parkinsonism, bucco-lingo-masticatory dyskinesia and bilateral extensor planter reflex were present, but tetany was not observed anywhere. Serum calcium was 3.9 mEq/l, and serum phosphorus 5.3 mEq/l. A CT scan of brain revealed calcifications in the bilateral basal ganglia and thalami, low density area in the left putamen, and atrophy of both caudate nuclei. Serum PTH was less than 100 pg/ml. Ellsworth-Howard's test showed hyperresponsiveness in the secretion of urinary phosphorus and cyclic-AMP. Other endocrinological studies showed no abnormality except for hyporesponsiveness in the secretion of insulin on glucose tolerance test. On the basis of these results, a diagnosis of idiopathic hypoparathyroidism with insulin-dependent diabetes mellitus was made. Administration of alfacalcidol returned serum calcium and phosphorus to normal with considerable clinical benefit. Parkinsonism was gradually improved and she became to be able to walk with a cane after one year of treatment. But buco-lingo masticatory dyskinesia were not reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225659 TI - [A case of Cogan's syndrome associated with multiple cranial neuropathy]. AB - A 52-year-old woman was admitted to our hospital because of disturbance of right visual acuity and double vision. At 38-year-old she became deaf bilaterally and experienced many vertigo attacks. She was diagnosed as Meniere disease. At 45 year-old vertigo attacks disappeared. At 47-year-old right peripheral facial nerve palsy developed transiently with interstitial keratitis and episcleritis of the both eyes. Oral adrenocorticosteroid therapy produced an improvement of interstitial keratitis and episcleritis. On admission, ophthalmological examination revealed bilateral interstitial keratitis and episcleritis, right retrobulbar optic neuritis and she was proven to have bilateral sensorineural deafness by otologist. Neurological examination revealed right abducens nerve paresis. Laboratory examinations revealed slightly increased erythrocyte sedimentation rate. CRP was positive. Serological tests for syphilis were negative. CSF showed mildly elevated protein level. Orbital CT scans revealed the swelling of right optic nerve. Cerebral MRI showed multiple high spotty areas in left thalamus, bilateral basal ganglia and deep white matter in T2 weighted images. After treatment with adrenocorticosteroid, right optic neuritis and abducens nerve paresis improved together with bilateral interstitial keratitis and episcleritis. Multiple cranial neuropathy may develop with Cogan's syndrome. PMID- 2225660 TI - [Duchenne muscular dystrophy carrier presenting with mosaic X chromosome constitution and muscular symptoms--with analysis of the barr bodies in the muscle]. AB - A 53-year-old female with muscular symptoms and incomplete Turner's syndrome was presented. She had two sons with Duchenne type muscular dystrophy (DMD). Her muscular symptoms became apparent at age 52 years, and her elevated serum CK, EMG and pathological findings of the biopsied muscle were consistent with muscular dystrophy. Her cytogenetic analysis from the cultured lymphocytes and fibroblasts showed a 45XO/46XX/47XXX chromosome constitution. Analysis of number of Barr bodies in the muscle specimen revealed that the total number of the bodies were significantly decreased in this case than in the control muscles. The result indicated that nuclei of 45XO karyotype were evidently present in her muscle and contributed to the process of muscle fiber breakdown as a major pathogenetic factor. However, inactivation of normal X chromosome also concerned the pathologic process because there were nuclei with Barr bodies in the damaged fibers as well. Only seven cases with X chromosome mosaicism and muscular symptoms attributable to DMD gene were seen in the literature. Four of them showed rather typical clinical features of DMD, but the muscular symptoms were much milder in the remainder, and patients were still able to walk in their middle lives. It was presumed that the severity of the clinical symptoms was parallel to the ratio of 45XO karyotype in the total number of muscular nuclei. PMID- 2225661 TI - [A case of juvenile Alzheimer's disease with various neurological features such as myoclonus, showing grumose degeneration in the dentate nucleus]. AB - A case of juvenile Alzheimer's disease with various neurological features such as myoclonus, also showing grumose degeneration in the dentate nucleus was reported. In a 35 year old woman, at first myoclonus, and 5 years later, progressive dementia were found. She, then, fell into apallic syndrome 9 years later, and died of pneumonia at the age of 53. She had no particular family history. Neurological examination disclosed cerebellar ataxia, left hemiparesis, convulsion in addition to myoclonus. Neuropathologically, there were a lot of senile plaques and neurofibrillary tangles in the cerebral cortex. A marked myelin loss in the white matter and a neuronal loss in the basal ganglia were also found. And grumose degeneration in the cerebellar dentate nucleus distinctively characterize the present case. The myoclonus and cerebellar ataxia could be attributed to the grumose degeneration. Two similar cases had been previously reported. Juvenile Alzheimer's disease with grumose degeneration like the present case was considered to be one of the subgroups of Alzheimer's disease. PMID- 2225662 TI - [A case of narcolepsy with increased cataplectic attacks after suffering from cerebrovascular disease]. AB - It is well known that narcoleptic patients have DR2 and DQw-1 on HLA typing. The development of narcolepsy is considered to depend on the two factors; genetic predispositions and exogenous factors such as head trauma, encephalitis, etc., mainly affecting the brainstem or diencephalon. We reported a 46-year-old man who had occasional sleep attacks after suffering from left thalamic hemorrhage and pontine vascular disorders. Rehabilitation was markedly disturbed due to frequent episodes of cataplectic attacks which was triggered by emotional lability such as laughing, anxiety, and excitement. HLA type examination showed both DR-2 and DQw 1 loci in the proband and his four other siblings. His elder brother also suffered from mild excessive daytime sleepiness during his younger age, but it subsided gradually. Analysis of overnight polysomnography in the patient revealed remarkable paradoxical alpha-blocking and frequent sleep onset REM stages as typically observed in narcoleptic patients. MRI examination showed multiple small hemorrhages and infarctions in the pontine tegmentum, in addition to the left thalamic hemorrhage and multiple subcortical ischemic lesions. Concerning the mechanism of frequent cataplexy in this patient, it is postulated that increased emotional incontinence might have stimulated the descending reticular system in the brainstem which in turn may inhibit anterior horn motor cell activities. Methylphenidate was initially given to the patient, resulting in some relief of attacks, and addition of imipramine dramatically suppressed cataplectic attacks. Imipramine is considered to inhibit the excitatory afferent pathway to the brainstem suppressing the hyperactivity of descending motor inhibitory system due to its anti-muscarinergic action. PMID- 2225663 TI - [MRI findings of the tongue in neurodegenerative diseases with bulbar sign]. AB - We examined the magnetic resonance image (MRI) of the tongue in cases of amyotrophic lateral sclerosis (ALS), bulbo-spinal muscular atrophy (SBMA) and Shy Drager syndrome (SDS) with sleep apnea. ALS case with severe bulbar disorder showed atrophic, irregularly margin tongue with increased signal intensity in T1 weighted MRI. ALS with less severe bulbar disorder demonstrated mixed hyperintensity and normointensity areas in the tongue. ALS without lingual symptoms showed increased intensity of tongue which suggested subclinical involvement of lingual muscle. BSMA case also showed atrophic tongue with diffusely increased signal intensity. SDS case with sleep apnea was revealed to have round shaped tongue without increased signal intensity, but his tongue fell into the posterior oral cavity, indicating hypotonus of genioglossus muscle. We concluded that MRI of the tongue is useful to determine the bulbar symptoms due to lower neuron disorder or not. PMID- 2225664 TI - [A microneurographic analysis of minor reflex sympathetic dystrophy with increased skin sympathetic activity--report of a case]. AB - A 48-year-old man developed swelling, redness, and allodynia in his left palm. Routine physical and neurological examinations revealed no abnormal findings except for left palmar hyperhidrosis. A clinical diagnosis of minor reflex sympathetic dystrophy with causalgia was made. Skin sympathetic activity (SSA), dominating palm sweating and skin vasoconstriction, and discharges of single afferent fiber from the rapidly adapting-type I (RA-I) unit were recorded microneurography from the median nerve at the cubital fossa. SSA obtained from the affected side was significantly increased compared with that from the normal (right) side. The receptive field of RA-I unit in this case was larger than those of normal controls. Enlargement of the receptive field might suggest presence of collateral sprouting in the injured nerve fibers. Allodynia in the left palm was suspected to be resulted from misdirect sprouting between A alpha . beta to A delta . C fibers. Excessive sympathetic out flow to the skin is considered to be the cause of palmar hyperhidrosis, swelling with redness, and lowered pain threshold, since pain threshold is under regulation of SSA. It is concluded that these sensory and autonomic symptoms were resulted from increased sympathetic out flow to the skin and collateral sproutings in the peripheral nerve fibers. PMID- 2225665 TI - [Vasopressin effect and pathophysiological analysis on postprandial hypotension]. AB - In order to clarify the effect of arginine vasopressin (AVP) on postprandial hypotension (PPH) in patients with multiple system atrophy, a loading test of 75 g glucose in 225 ml water was performed during infusion of AVP (0.3 U/min). AVP (0.3 U/min) infusion prior to the loading was significantly effective for PPH in all patients: PPH following to oral intake of glucose was completely prevented. We conclude that infusion of AVP maintained circulating systemic blood volumes by reduced portal venous flow (after a reduction of portal venous inflow) as a result of vasoconstrictive effect of AVP on the splanchnic vessels in patients with PPH. PMID- 2225666 TI - Incidental demonstration of cerebral infarction on bone scintigraphy in sickle cell disease. PMID- 2225667 TI - Hepatic infarction detected on Tc-99m sulfur colloid imaging. AB - Hepatic infarctions are rarely encountered, and scintigraphic findings are reported even less frequently in this entity. A patient who developed a left hepatic lobe infarct after surgical resection of a celiac axis aneurysm is described and a brief review of hepatic infarction is presented. PMID- 2225668 TI - Fractionated doses of radioiodine for ablation of postsurgical thyroid tissue remnants. AB - Patients who have differentiated thyroid carcinoma and have undergone total thyroidectomy are treated with radioiodine for ablation of functional thyroid remnants. Administration of a single therapeutic dose in excess of 30 mCi of l 131 requires hospitalization. In an attempt to obviate the necessity for hospitalization, the prospective ablative dose was divided into two or three fractions given at weekly intervals on an ambulatory basis. To assess the effectiveness of this approach, this group of patients was compared to a cohort of hospitalized patients treated with a single dose. Ablation was achieved in 9 out of 12 patients treated in a fractionated manner (a 75% success rate), whereas in 16 out of 20 patients given a single dose the thyroid remnants were completely eradicated (an 80% success rate). That the use of split, smaller doses administered at weekly intervals on an ambulatory basis presents a reasonable alternative for ablation of postsurgical, residual-functioning thyroid tissue. PMID- 2225669 TI - The incidence of serious hemodynamic changes in physically-limited patients following oral dipyridamole challenge before thallium-201 scintigraphy. AB - Dipyridamole has liberalized referrals for stress TI-201 chloride (thallium) studies at the Iowa City Veterans Administration Medical Center. Seventy-five percent of referrals now receive dipyridamole and, unlike patients who tolerate conventional exercise testing, these patients are often quite debilitated. Therefore, the hemodynamic consequences of dipyridamole were reviewed in 120 consecutive, physically-limited patients referred for thallium scintigraphy following an average oral dose of 5.4 mg/kg. Each patient's blood pressure was measured every 5 minutes for 1 hour after dipyridamole and compared with several clinical factors to determine if blood pressure change was predictable. In all patients, blood pressure changed from 136 +/- 21/83 +/- 15 (mean +/- 1 SD) to 117 +/- 25/72 +/- 15 following dipyridamole administration. One hundred nine of the 120 patients had a blood pressure decline from 137 +/- 21/82 +/- 12 to 113 +/- 21/70 +/- 13. Of the 109, 43% (N = 47) had a systolic blood pressure decline greater than 20 mmHg, 16% (n = 18) greater than 40 mmHg, and 13% (n = 14) greater than 50 mmHg. Thirteen percent (n = 14) required emergent reversal of the dipyridamole with aminophylline. Significant hypotension is relatively common but generally unpredictable after oral dipyridamole. Therefore, patient eligibility criteria should be carefully considered; strict hemodynamic monitoring must be routine in the usual patient undergoing thallium scintigraphy after oral dipyridamole challenge. PMID- 2225670 TI - Ventilation-perfusion scintigraphy in an adult with congenital unilateral hyperlucent lung. AB - A variety of congenital and acquired etiologies can give rise to the radiographic finding of a unilateral hyperlucent lung. An unusual case of congenital lobar emphysema diagnosed in a young adult following the initial discovery of a hyperexpanded, hyperlucent lung is reported. Although subsequent bronchoscopy and radiologic studies detailed extensive anatomic abnormalities, functional imaging also played an important role in arriving at this rare diagnosis. In particular, ventilation-perfusion scintigraphy identified the small contralateral lung as the functional lung and helped narrow the differential diagnosis to etiologies involving obstructive airway disorders. PMID- 2225671 TI - Effect of proximal vagotomy and Roux-en-Y diversion on gastric emptying kinetics in asymptomatic patients. AB - The role of the distal stomach in gastric emptying was studied. Ten patients with proximal gastric vagotomy (PV) and 10 age-matched patients with Roux-en-Y gastro jejunostomy (R-Y) were compared with 10 healthy controls. Gastric emptying of solids and liquids was determined by the use of Tc-99m SC scrambled eggs and In 111 DTPA. In PV, gastric emptying of both solids and liquids was delayed; the prolongation with solids was mainly accounted for by an abnormal lag phase. In R Y patients, no lag phase was observed, and the solid emptying curve pattern was characterized by early rapid emptying followed by very slow emptying. Both the solid and liquid phases were prolonged. The lag phase is affected by proximal vagotomy and is mainly determined by the distal stomach, which appears to be essential for normal emptying. PMID- 2225672 TI - Metastatic calcification in a patient with malignant parathyroid carcinoma. Correlation of clinical, surgical, radiographic, and scintigraphic findings. AB - A patient whose bone scan showed features typical of a "superscan," having extensive pulmonary, cardiac, and renal calcifications is described. Metastatic parathyroid carcinoma with renal insufficiency and phosphate retention are cited as the cause. Early diagnosis and surgical extirpation offer the best chance for cure or palliation. Pitfalls of plain film radiography in identifying metastases and pathologic soft tissue calcifications in the setting of severe hyperparathyroidism are discussed, and the advantages of functional radionuclide imaging assessments are emphasized. PMID- 2225673 TI - Heterotopic ossification. Effect on dual-photon absorptiometry of the hip. AB - Dual-photon absorptiometry (DPA) is now widely used to determine bone mineral density of the lumbar spine and hips. Because the resulting images are often not of sufficient resolution to identify many bone or soft tissue abnormalities that may influence results, clinical and radiographic correlation is necessary. Presented are two cases in which results of DPA of the hips were elevated because of the presence of heterotopic ossification. PMID- 2225674 TI - A porcelain gallbladder affecting the assessment of bone mineral content. AB - Dual-photon absorptiometry is a reliable method for the assessment of bone mineral content (BMC). The presence of focal bone disease, degenerative joint disease, or aortic calcifications may complicate the evaluation of BMC and may lead to erroneous findings. The misleading effect of a porcelain gallbladder is described. PMID- 2225675 TI - Deposition of radioaerosol throughout the major airways in tracheobronchitis. PMID- 2225676 TI - Breast uptake of gallium-67 citrate in disseminated Mycobacterium chelonei. PMID- 2225677 TI - Intravenous dipyridamole thallium-201 SPECT imaging methodology, applications, and interpretations. AB - Dipyridamole TI-201 imaging is an ideal alternative to exercise TI-201 scintigraphy in patients who are unwilling or unable to perform maximum exercise stress. The use of intravenous dipyridamole, alone or in combination with exercise, has not been approved for clinical practice by the Food and Drug Administration. Once approval is granted, the test will become a widely used and important component of the cardiac work-up. The indications, methodology, side effects, and utility of dipyridamole cardiac imaging in the clinical setting are discussed and a variety of examples presented. PMID- 2225678 TI - Intravenous dipyridamole. Reflections while waiting for FDA approval. PMID- 2225679 TI - Bone scan abnormalities in a child with Lyme disease. PMID- 2225680 TI - Insufficiency fractures of the upper femurs. Five-year lapse between occurrence on opposite sides. PMID- 2225681 TI - Rapid detection of a giant aneurysm of right sinus of Valsalva by radioisotopic angiography. PMID- 2225682 TI - Intense Tl-201 uptake in a "cold" bone lesion due to metastatic thyroid carcinoma. PMID- 2225683 TI - Tc-99m MDP accumulation in lymphoma. PMID- 2225684 TI - Bone scan in inferior vena cava obstruction. PMID- 2225685 TI - Renal uptake of Tc-99m sulfur colloid in disseminated intravascular coagulation. PMID- 2225686 TI - Clinical approach to prenatal detection of human structural defects. AB - Tremendous advances in prenatal diagnosis have allowed clinicians to recognize a variety of structural defects in the developing fetus. Guidelines for fetal ultrasonography and an approach to fetal evaluation are outlined. The developmental morphologic approach is emphasized as a way of categorizing congenital anomalies whether they are detected during prenatal or postnatal life. The use of this approach for diagnosing and managing fetal malformation syndromes is illustrated. PMID- 2225687 TI - Teratogenically induced fetal anomalies. AB - A variety of infectious and physical agents, maternal diseases and altered metabolic states, and drugs and chemicals have been shown to cause postnatal structural or functional disabilities when embryonic or fetal exposure occurs during human pregnancy. These disabilities are potentially preventable through public education and awareness. Health-care providers must be equipped to collect relevant data regarding exposures of concern from their pregnant patients, locate and evaluate pertinent current teratology information resources, and sensitively counsel these women regarding the associated potential teratogenic risks. Comprehensive care of the patient exposed to a human teratogen may also include discussion of prenatal diagnostic procedures and other pregnancy management options. PMID- 2225688 TI - Aberrant morphogenesis of the central nervous system. AB - This overview of congenital defects of the CNS has emphasized pathogenesis. As developmental pathways continue to be elucidated, this approach remains to an extent hypothetical. When, however, an understanding of the features of morphogenesis and dysmorphogenesis helps to indicate time of onset or to elucidate causal factors, important steps toward the prevention of birth defects are taken. PMID- 2225690 TI - Posterior nuchal cystic hygroma. AB - When cystic hygroma is detected antenatally, the prognosis is usually poor, and intrauterine or neonatal death are common. This seems especially true for Turner syndrome (the largest etiologic group associated with cystic hygroma) and the lethal multiple pterygium syndromes. However, some fetuses with Turner syndrome, and also with certain other diagnoses, had a good outcome, and further study of these conditions is required before more definite prognostic indicators and risk figures will be available. Increasing numbers of syndromes are being reported in association with fetal cystic hygroma, and lymphedema may be a common element in their pathogenesis. Mild, short-lived, or otherwise uncomplicated jugular lymphatic obstruction may be a cause of the neck webbing seen in the Noonan, familial pterygium colli, and distichiasis-lymphedema syndromes. With earlier and more widespread fetal ultrasonography, and more sensitive techniques, a greater number of resolving fetal cases may be reported. This may clarify the natural history and provide prospective criteria for the conditions that have better prognoses. The associated conditions include autosomal dominant and recessive genetic traits. Careful ultrasound study for other malformations, polyhydramnios and fetal growth parameters, a fetal karyotype, and, if appropriate, pathologic examination are required to determine the etiology and recurrence risk. The parents should be asked about exposure to alcohol or other agents and should be examined for signs of pterygium colli or Noonan syndrome. If the decision is made to continue the pregnancy, and there is doubt about the natural history and prognosis, multi-disciplinary supervision should include social services, neonatology, pediatric surgery, cardiology, and genetics specialties when indicated. PMID- 2225689 TI - Ultrasound imaging of the cranium and spine. AB - A general description and discussion of the normal head and spine, and major fetal anomalies has been presented. It is important to remember that there can be wide variability in the structural findings noted in the fetus with ventricular dilatation or abnormal cerebellar development. If an abnormality of the fetal head and spine is seen, it is important to carefully assess other areas of fetal anatomy because of the increased likelihood of coexisting anomalies. Because of the increased incidence of chromosomal abnormalities, evaluation by percutaneous umbilical blood sampling, amniocentesis or placental biopsy is recommended for all structural abnormalities of the fetal head and spine. The best clinical approach for the ultrasonologist is to accurately describe and quantify the abnormalities for geneticist, pediatrician and or neurosurgeon to discuss the prognosis. Accurate evaluation of the type, location and extent of a neural tube defect is important to enable the family to understand possible outcomes of the pregnancy. PMID- 2225691 TI - Congenital heart defects in malformation syndromes. AB - This article presents a comprehensive review of the type and frequency of congenital heart defects found in malformation syndromes which have been categorized by etiology. Certain cardiac phenotypes can be as helpful in identifying certain syndromes as can be seen with the more familiar facial, body, and behavioral phenotypes. An awareness of syndromes with a higher risk of congenital heart defect, and knowledge concerning heart defects which are distinctive for certain syndromes, focuses prenatal diagnosis efforts and fetal echocardiography. By using a mechanistic classification in which congenital heart defects are regarded as families of related defects rather than individual lesions, patterns can be recognized among different syndromes. PMID- 2225692 TI - Fetal abdominal abnormalities associated with genetic syndromes. AB - Sonographic technology has given the prenatal diagnostician the ability to accurately visualize fetal malformations. This article demonstrates the currently available capability of applying sonographically derived information concerning fetal dysmorphology to our knowledge of genetic disorders and syndromes. As a result, there can be a significant improvement in the management and counseling of these patients. After an initial discussion of normal embryology, principles of abdominal ultrasonography are discussed and applied to the following anomalies: omphalocele, gastroschisis, diaphragmatic hernia, duodenal atresia, other intestinal atresias and stenoses, renal anomalies, and obstructive uropathies. PMID- 2225693 TI - Fetal imaging in the skeletal dysplasias. AB - Second-trimester diagnosis of fetal skeletal dysplasia is becoming increasingly common. By careful examination of the fetus for skeletal mineralization, shape and size of long bones and cranium, and abnormalities of other organ systems, a definitive diagnosis can often be achieved by ultrasound. Fetal radiography is very helpful in giving more information about bone shape and mineralization as well as in confirming the diagnosis. Subsequent obstetric management should be dictated by the natural history of the disease, the parents' wishes, and the gestational age at diagnosis. Because many of these disorders have a high recurrence risk, genetic counseling and follow-up are an important part of the management of these patients. PMID- 2225695 TI - How to interpret studies of adverse drug reactions. PMID- 2225694 TI - A protocol for the investigation of pregnancy loss. AB - A protocol for the evaluation of pregnancy loss should include a maternal history, dysmorphic examination of the fetus or abortus, photographs, autopsy, chromosome studies (in most cases), and radiographic or xeroradiographic studies. Selected cases with suspected ascending or transplacental infection may require microbiologic investigation. Increasing specialized laboratory techniques may help in the diagnosis of inborn errors of metabolism or storage disorders. Coordination of studies requires the interaction of OB/GYN, pathology, genetics, cytogenetics, and nursing in order to assure delivery of this clinical service. Knowledge of the causes of pregnancy loss and their typical time and mode of presentation can facilitate a focused evaluation, with a high chance of achieving an accurate diagnosis. The goal of all investigations is to provide families with recurrence risk data on which to base future childbearing decisions, as well as information on potential prenatal monitoring. PMID- 2225696 TI - Kinetic effects of multiple oral doses of acetaminophen on a single oral dose of lamotrigine. AB - In this double-blind, randomized, crossover, placebo-controlled study, the effect of multiple oral doses of acetaminophen on lamotrigine disposition was examined in healthy volunteers. Eight volunteers received two single 300 mg oral doses of lamotrigine, administered 20 days apart. Acetaminophen (2.7 gm/day) or placebo was taken for 24 hours before and continued for 10 days after each lamotrigine dose. Area under the plasma concentration-time curve for lamotrigine [AUC(O infinity)] and lamotrigine half-life were statistically decreased by 20% (229.0 +/- 62.5 micrograms.hr/ml versus 191.2 +/- 42.1 micrograms.hr/ml, p less than 0.01) and 15% (35.7 +/- 9.3 hours versus 30.2 +/- 7.3 hours, p less than 0.01), respectively, when concurrently administered with acetaminophen. There was no significant difference in the peak plasma concentration or the time to reach peak plasma concentration. The percentage of the dose of lamotrigine recovered in the urine (total) was significantly higher during the acetaminophen treatment (65.9% +/- 12.3% versus 72.5% +/- 5.7%, p = 0.048). Acetaminophen seems to facilitate lamotrigine removal through a yet to be determined mechanism(s). PMID- 2225697 TI - Exercise hemodynamics and catecholamine metabolism after catechol-O methyltransferase inhibition with nitecapone. AB - The effect of catechol-O-methyltransferase inhibition with nitecapone (OR-462) on the hemodynamic responses to exercise and catecholamine metabolism was studied in 10 healthy male volunteers (aged 19 to 26 years). Nitecapone, a new specific and selective catechol-O-methyltransferase inhibitor, was given at increasing single oral doses up to 100 mg. Nitecapone did not influence resting or exercise heart rate, blood pressure, systolic time intervals, or plasma catecholamine levels. It altered the metabolic profile of catecholamines as shown by (1) an increase of 140% in the plasma concentration of the monoamine oxidase-dependent metabolite 3,4-dihydroxyphenylethyleneglycol (p less than 0.001), (2) a decrease of 27% in the plasma concentration of its methylation product 3-methoxy-4 hydroxyphenylethyleneglycol (p less than 0.05), and (3) a 25% reduction in the urinary excretion of the methylated metabolites 3-methoxy-4-hydroxymandelic acid and homovanillic acid (p less than 0.05). Nitecapone was well tolerated and seemed to be hemodynamically safe in humans. PMID- 2225698 TI - Human liver catechol-O-methyltransferase pharmacogenetics. AB - Catechol-O-methyltransferase activity and thermal stability in the human red blood cell are controlled by a common genetic polymorphism. Approximately 25% to 30% of a randomly selected population sample is homozygous for the traits of low catechol-O-methyltransferase activity and thermolabile enzyme in the red blood cell. We tested the hypothesis that the catechol-O-methyltransferase genetic polymorphism might also control those same characteristics of the enzyme in an important human drug-metabolizing organ, the liver. Catechol-O-methyltransferase enzyme activity and thermal stability were measured in 99 hepatic biopsy samples obtained during clinically indicated surgery. The frequency distribution of heated/control ratios, a measure of enzyme thermal stability, was bimodal, with 28% of samples included in a subgroup with thermolabile enzyme. There were no sex related differences in hepatic catechol-O-methyltransferase thermal stability. However, catechol-O-methyltransferase enzyme activity in hepatic tissue from male subjects was significantly higher than that in samples from female subjects: 61.3 +/- 20.2 units/mg protein (mean +/- SD; n = 50) versus 46.6 +/- 22.2 units/mg protein (n = 49; p = 0.0002). There was a significant correlation of hepatic catechol-O-methyltransferase activity and thermal stability in samples from both female (rs = 0.698; p = 0.0001) and male subjects (rs = 0.429; p = 0.002). Finally, when both red blood cell catechol-O-methyltransferase activity and thermal stability were measured in blood samples from 34 of these patients, there was a significant correlation between catechol-O-methyltransferase heated/control ratios and levels of enzyme activity in hepatic tissue and in red blood cell lysates. These findings indicate that the genetic polymorphism that controls catechol-O-methyltransferase activity level and thermal stability in red blood cells also controls those same properties of the enzyme in the human liver. PMID- 2225699 TI - Monitoring glucocorticoid therapy: a pharmacokinetic approach. AB - Although glucocorticoid therapy is essential for the treatment of severe inflammatory disorders, there is no systematic approach to patient variables that may affect availability of a steroid dose. After the development of a data base of pharmacokinetic parameters, we examined glucocorticoid pharmacokinetics in 54 patients between 2 and 70 years of age using 70 pharmacokinetic studies after administration of intravenous methylprednisolone (n = 25), oral methylprednisolone (n = 15), intravenous prednisolone (n = 18), and oral prednisone (n = 12). Eleven patients had unusually rapid methylprednisolone elimination (clearance, 565 to 837 ml/min/1.73 m2; population mean, [+/- SD] 380 +/- 100 ml/min/1.73 m2) without an identifiable cause. Incomplete absorption of methylprednisolone and prednisone was observed in three patients and one patient, respectively. Evaluation of glucocorticoid pharmacokinetics in children aged 1 year 8 months to 18 years demonstrated a significant inverse correlation (r = 0.88; p less than 0.001) between prednisolone clearance and age. It is therefore important to consider age in the interpretation of pharmacokinetic data. To simplify measurement of prednisolone clearance, a single-dose single-point method was developed. This was based on a highly significant relationship between the 6 hour postdose prednisolone concentration and prednisolone clearance (log prednisolone clearance = 2.66 + [6-hour postdose concentration] [-0.00167]; r2 = 0.96; p less than 0.0001). Evaluation of glucocorticoid pharmacokinetics in the clinical setting can be used to identify abnormalities in absorption, elimination, and patient compliance. This technique can be used to individualize glucocorticoid dosing regimens. PMID- 2225700 TI - Mefloquine kinetics in cured and recrudescent patients with acute falciparum malaria and in healthy volunteers. AB - Mefloquine pharmacokinetics were compared in a randomized clinical trial in Thailand among patients with malaria and healthy volunteers. A single oral dose of 1500 mg mefloquine hydrochloride was administered to 11 patients and 5 volunteers and 750 mg was given to 16 patients and 5 volunteers. Efficacy was 82% for 1500 mg and 63% for 750 mg. In cured patients taking 750 mg mefloquine, peak plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) were significantly greater than in the patients for whom treatment failed (p less than 0.0005 and p less than 0.01, respectively), and plasma mefloquine levels were significantly higher from 8 hours to 18 days after treatment. Mefloquine AUC was reduced and variable in the presence of diarrhea. Compared with noninfected volunteers, clinically ill patients displayed a delayed time to reach peak concentration (p less than 0.01) and significantly higher mefloquine plasma levels in the first 2 days after administration of either the 750 mg or the 1500 mg dose. Mefloquine AUC was similar in patients with malaria and healthy volunteers. Because plasma levels increased in temporal relationship with clinical illness, mefloquine volume of distribution or clearance (or both) was reduced during the acute phase of illness. PMID- 2225701 TI - Caffeine and theophylline attenuate adenosine-induced vasodilation in humans. AB - In this study the local vasoactive effects of adenosine were explored in the human forearm. Adenosine (15 micrograms/100 ml forearm/min) infused into the brachial artery (n = 6) increased forearm blood flow by 572% +/- 140%, versus - 0.5% +/- 5.8% during placebo infusion (p less than 0.01). Lower adenosine infusion rates (5 micrograms/100 ml forearm/min, three times) induced forearm blood flow increments to 330% +/- 94%, 339% +/- 67% and 330% +/- 79%, respectively (n = 8). These forearm blood flow responses were reduced (p = 0.02) during concomitant intra-arterial infusion of two doses of caffeine (30 and 90 micrograms/100 ml forearm/min) to 150% +/- 45% and 98% +/- 28%, respectively. Theophylline (30 micrograms/100 ml forearm/min; n = 6) also significantly attenuated the adenosine-induced increase in forearm blood flow. Enprofylline (30 micrograms/100 ml forearm/min), a related xanthine with a low affinity to adenosine receptors in vitro, did not change the response to adenosine. Nonspecific vasodilation by sodium nitroprusside infusion (50 ng/100 ml forearm/min) was not inhibited by caffeine compared with placebo (forearm blood flow responses were 202% +/- 21% versus 216% +/- 40%; n = 6). This study demonstrated that caffeine and theophylline specifically reduce adenosine-induced vasodilation in humans, supporting the existence of functional human vascular adenosine receptors. PMID- 2225702 TI - The antihypertensive efficacy of hydrochlorothiazide is not prostacyclin dependent. AB - We tested the hypothesis that vascular prostacyclin synthesis is stimulated by hydrochlorothiazide and could account for some of the drug's antihypertensive effect. We studied 13 patients with mild essential hypertension in a randomized, double-blind design to assess the effects of indomethacin on hydrochlorothiazide's ability to lower blood pressure, alter body weight, stimulate plasma renin activity, and modulate vascular prostacyclin biosynthesis as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha), measured by GC/MS. Administration of hydrochlorothiazide, 50 mg daily for 2 weeks, was associated with a significant decrease in both systolic and diastolic blood pressure in both supine (systolic, 148 +/- 3 to 136 +/- 3 mm Hg; diastolic, 97 +/- 2 to 94 +/- 3 mm Hg) and upright (systolic, 151 +/- 4 to 131 +/- 2 mm Hg; diastolic, 103 +/- 2 to 97 +/- 3 mm Hg) positions. Hydrochlorothiazide administration resulted in a 1 kg weight loss and stimulation of plasma renin activity from 1.7 +/- 0.4 to 5.3 +/- 1.1 ng angiotensin I/ml/hr. However, the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha was unchanged after administration of hydrochlorothiazide (86 +/- 13/ng/gm creatinine during placebo, 74 +/- 13 ng/gm during week 1 of hydrochlorothiazide, and 70 +/- 9 ng/gm during week 2 of the drug). Administration of indomethacin, 50 mg twice a day, resulted in greater than 60% inhibition of 2,3-dinor-6-keto-PGF1 alpha excretion but did not affect the antihypertensive response to hydrochlorothiazide. Indomethacin did not oppose the diuretic effect of hydrochlorothiazide as assessed by weight loss but did attenuate the rise in plasma renin activity. Our data demonstrate that the blood pressure-lowering effect of a thiazide diuretic does not require enhanced prostacyclin synthesis and the cyclooxygenase inhibitor indomethacin does not antagonize the antihypertensive efficacy of hydrochlorothiazide. PMID- 2225703 TI - Pharmacodynamics of propranolol on left ventricular function: assessment by Doppler echocardiography. AB - The relationship of left ventricular systolic function and heart rate to serum l propranolol concentrations was determined in 10 healthy male volunteers during maximal exercise treadmill testing. Peak aortic blood flow acceleration (ACL), measured by Doppler ultrasonography, was used to evaluate left ventricular systolic function. Repeated exercise testing was performed on two separate days after long-term oral administration of 40 mg propranolol or placebo every 6 hours in a randomized, double-blind, crossover fashion. Pharmacodynamic relationships were determined by fitting percent change in ACL and heart rate at maximal exertion with 1-propranolol with the Emax model (maximal effect) and nonlinear regression. Reductions in systolic function and heart rate during exercise were related directly to 1-propranolol. Propranolol was significantly (p less than 0.05) more potent in reducing heart rate (EC50, 10.6 +/- 9.2 ng/ml) compared with ACL (EC50, 19.2 +/- 8.9 ng/ml). However, Emax of propranolol for reducing ACL was significantly greater than that for reducing heart rate (-46.7% +/- 6.9% versus 29.5% +/- 15.9%; p less than 0.05). These data indicate that the concentration effect relationship for 1-propranolol and its negative inotropic effect differ from its negative chronotropic effect. PMID- 2225704 TI - Suppression of deferoxamine mesylate treatment-induced side effects by coadministration of isoniazid in a patient with Alzheimer's disease subject to aluminum removal by ionspecific chelation. AB - Deferoxamine treatment may produce serious side effects that can be eliminated by modification of treatment and by control of deferoxamine metabolism. A patient suffering from dementia of the Alzheimer type with normal liver and kidney function who was treated with deferoxamine initially tolerated a dose of 7 mg/kg deferoxamine mesylate injected intramuscularly twice a day for a total of 5 days a week. After several months nausea and weight loss gradually developed in the patient that could be controlled initially by dose reduction, leading to levels inappropriate for aluminum chelation. HPLC analysis of blood and urine revealed several metabolites including, as a major component, a plasma monoamine oxidase (MAO) catalyzed end product MFO1. Coadministration of isoniazid, a plasma MAO inhibitor, with deferoxamine resulted in reduction of MFO1 from 81% to 8% accompanied by increases in the amounts of metabolite 2 (MFO2) from 2% to 24% and unmetabolized deferoxamine from 17% to 68% after 6 months of treatment. The side effects subsided, the patient regained weight, and treatment could be continued. PMID- 2225705 TI - Quality of life among hypertensive patients with a diuretic background who are taking atenolol and enalapril. AB - The cardioselective beta-blocker atenolol and the angiotensin-converting enzyme inhibitor enalapril were compared for efficacy, safety, and quality-of-life factors in 30 patients with hypertension whose hypertension was inadequately controlled with diuretic alone. Atenolol (50 to 100 mg once a day) and enalapril (2.5 to 40 mg once a day), combined with hydrochlorothiazide (25 mg once a day), had similar levels of efficacy and safety. A comprehensive battery of psychologic assessments for quality of life was administered, including measures of anxiety, depression, psychiatric symptoms, memory, and psychomotor function. These five conceptually based clusters were first analyzed by multivariate analysis of variance procedures, followed by univariate analyses of the individual variables composing each domain. In general, neither atenolol nor enalapril was associated with major changes in psychologic functioning. The only data cluster with a statistically significant change was memory function, primarily as a result of lower scores of the digit span (backward) test, for atenolol relative to enalapril. These preliminary findings suggest that atenolol and enalapril have comparable degrees of efficacy and safety, with no major disparities in quality of-life effects, for hypertensive patients with a history of taking diuretics and this sort of quality-of-life assessment can be performed during trials of antihypertensive drugs. PMID- 2225706 TI - Does alternate-day cloprednol therapy prevent bone loss? A longitudinal double blind, controlled clinical study. AB - Osteoporosis is a serious side effect of systemic treatment with steroids. Cloprednol, a synthetic glucocorticoid with an anti-inflammatory potency twice that of prednisone, causes less calcium and nitrogen excretion than does prednisone in equipotent doses. Therefore a double-blind study was undertaken comparing the effects of alternate-day cloprednol and prednisone therapy on bone mineral density in 39 patients (cloprendol: 13 men and 8 women aged 48.5 +/- 2.8 years; prednisone: 9 men and 9 women aged 49.7 +/- 1.7 years) with lung diseases. Ten patients with asthma (9 men and 1 woman aged 37.8 +/- 3.7 years) inhaling daily beclomethasone served as control subjects. Trabecular and total bone density of the distal tibia and radius was determined quarterly during 1 year with a special-purpose computed tomographic system. Initial mean trabecular bone density of the patients receiving cloprednol and prednisone was 17% below normal. After a treatment period of 1 year, we found a loss of radial trabecular bone density (mean +/- SEM) of 1.33% +/- 0.49% in the cloprednol group and 2.38% +/- 0.69% in the prednisone group. In postmenopausal women, prednisone but not cloprednol therapy caused significant (p less than 0.01) trabecular bone loss (5.29% +/- 0.99% versus 0.70% +/- 0.65%). The control group lost 0.91% +/- 0.79%. Loss of cortical bone was insignificant in all three groups. In post-menopausal women, 1 year of alternate-day cloprednol therapy was associated with significantly less bone loss than was prednisone therapy in equipotent dosages. PMID- 2225707 TI - Effects of lovastatin in diabetic patients treated with chlorpropamide. AB - Patients with non-insulin dependent diabetes mellitus (NIDDM) have a higher risk of atherosclerotic cardiovascular disease than nondiabetic subjects. In seven patients with both hypercholesterolemia and NIDDM controlled by chlorpropamide, lovastatin (20 mg b.i.d. for 6 weeks) lowered low-density lipoprotein cholesterol by 28%, total cholesterol by 24%, and apolipoprotein B by 24%. Lovastatin levels for a 4-hour period (measured as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitory activity) were similar to those measured previously in nondiabetic patients. Lovastatin did not alter chlorpropamide kinetics or glycemic profiles. No patient had an elevation in serum transaminases or creatinine phosphokinase, and no patient had any other laboratory or clinical drug-related adverse experience during the study. Lovastatin was as effective in reducing low-density lipoprotein cholesterol in patients with NIDDM as in nondiabetic subjects. Diabetic control was unaltered, and no evidence of alteration in lovastatin or chlorpropamide blood levels was noted. PMID- 2225708 TI - Nicotine metabolism in nonsmokers. PMID- 2225709 TI - Diazepam metabolism in native Chinese poor and extensive hydroxylators of S mephenytoin: interethnic differences in comparison with white subjects. AB - A single oral 5 mg dose of diazepam was given to 16 healthy native Chinese Han volunteers. Eight volunteers were extensive metabolizers of S-mephenytoin, and eight were poor metabolizers of S-mephenytoin. Plasma levels of diazepam and its demethyl metabolite were determined by HPLC in blood samples drawn during 4 weeks. There was no difference in diazepam disposition between the two phenotypes. However, the plasma half-life of demethyldiazepam was longer in poor metabolizers than in extensive metabolizers of mephenytoin (mean +/- SD: 161 +/- 37 and 116 +/- 29 hours, respectively; p less than 0.02). The plasma concentrations of demethyldiazepam at 7, 14, and 21 days after intake of diazepam were significantly higher in poor metabolizers than in extensive metabolizers. We compared the pharmacokinetic parameters of diazepam in Chinese subjects with our previously reported data from white subjects. The mean plasma half-life values of diazepam in Chinese extensive metabolizers (85.1 hours) and poor metabolizers (88.3 hours) were very similar to those in white subjects who were poor metabolizers (88.3 hours), and more than twice those in white subjects who were extensive metabolizers (40.8 hours). In parallel, the mean clearance of diazepam in Chinese subjects (independent of phenotype) was similar to that in white subjects who were poor metabolizers, but half that in white subjects who were extensive metabolizers. Chinese subjects had a slightly larger volume of distribution of diazepam than white subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2225710 TI - Validity of creatinine clearance estimates in the assessment of renal function. AB - In clinical practice, estimations of renal function are commonly used to calculate the appropriate dose for drugs that are renally cleared. Continuous infusion inulin clearance (CLIN), 4-hour creatinine clearance (CLCR,m), and 24 hour creatinine clearance (CLCR,a) were measured in 109 subjects (86 men and 23 women) with varying degrees of stable renal function (CLIN, 6 to 209 ml/min) and compared with CLCR values as predicted by five equations on the basis of plasma creatinine concentrations, age, weight, and/or height. The CLCR,m was positively correlated with CLIN (r = 0.92; p less than 0.0001) but exceeded CLIN by 15% between the range of 30 and 209 ml/min (CLIN). Similarly, CLCR,a correlated well with both CLCR,m (r = 0.84; p less than 0.0005) and CLIN (r = 0.84; p less than 0.0001). The relative role of tubular secretion in the overall clearance of creatinine increased with declining CLIN and exceeded 40% when CLIN was below 30 ml/min. CLCR estimated by the Cockcroft-Gault and Mawer methods did not significantly differ from either CLCR,m or CLCR,m, whereas the other equations generally underestimated CLCR. Among the numerous mathematical equations, CLCR as estimated by the method proposed either by Mawer or Cockcroft and Gault was the best predictor of CLIN (CLIN = 1.05CLRCR - 18.38 or CLIN = 1.12CLCR - 20.60, respectively; r = 0.81; p less than 0.0001). The present data support the use of estimator equations proposed by Cockcroft and Gault or Mawer for rapid estimation of renal function in the clinical setting. PMID- 2225711 TI - Labetalol pharmacokinetics and pharmacodynamics: evidence of stereoselective disposition. AB - Labetalol pharmacokinetics and pharmacodynamics were evaluated in nine subjects before and during enzyme inhibition with cimetidine. Pharmacologic response was assessed by use of standardized treadmill tests during 24 hours after administration of oral labetalol. Oral clearance of labetalol decreased with cimetidine administration (58.7 +/- 23.3 to 32.9 +/- 13.2 ml/min/kg; p less than 0.05), thereby causing a 79% increase in area under the curve. Labetalol systemic clearance also decreased (23.2 +/- 5.3 to 17.7 +/- 3.7 ml/min/kg; p less than 0.05), but the volume of distribution was unchanged. Labetalol caused significant beta-blockade for 8 hours after the last oral dose, but cimetidine did not alter pharmacologic response. The Emax model provided a good description of the concentration-effect relationship. At peak labetalol concentrations after oral administration, (R,R)-labetalol concentrations were significantly lower than those of the other three stereoisomers (p less than 0.05). Cimetidine caused an increase in the concentrations of each stereoisomer, but the difference was significant (p less than 0.05) for only the (S,R)-, (S,S)-, and (R,S)-isomers. This first evidence of labetalol stereoselective disposition is consistent with the findings of previous (R,R)-labetalol pharmacokinetic studies and with previous pharmacodynamic investigations of labetalol and (R,R)-labetalol. PMID- 2225712 TI - Influence of the menstrual cycle on the absorption and elimination of D-xylose. AB - Thirteen healthy female volunteers with regular menstrual cycles (28 +/- 2 days) received 25 gm oral and 5 gm intravenous doses of D-xylose on 2 successive days during the follicular, ovulatory, and luteal phases of two consecutive menstrual cycles. The ovulation time was characterized by luteinizing hormone levels, body basal temperatures, and progesterone and estradiol serum levels. D-Xylose was assayed in plasma and urine with a phloroglucinol-based colorimetric method. The findings of this study indicated that menstrual cycle did not significantly affect D-xylose absorption. After oral administration, the total clearance was significantly increased in cycle 2 during the luteal phase (p = 0.004). After intravenous administration in both cycles, D-xylose total clearance was also significantly faster during the luteal phase (p = 0.038 and p = 0.041, respectively). After oral administration, the renal clearance tended to be higher during the luteal phase in both cycles studied. After intravenous administration, this parameter was increased during the luteal phase by 24% and 25% in cycle 1 and by 8% and 12% in cycle 2. These findings are consistent with those of others showing an increase in glomerular filtration rate (GFR) during the luteal phase of the menstrual cycle. The findings of this study seem to be explained by the hormonal changes occurring during the menstrual cycle. Further investigations are warranted with use of specific probes of renal processes (GFR, renal reabsorption and tubular secretion) to confirm our findings and to elucidate the underlying mechanisms. PMID- 2225713 TI - Electroencephalographic effects of benzodiazepines. I. Choosing an electroencephalographic parameter to measure the effect of midazolam on the central nervous system. AB - The goal of this investigation was to determine a numerical electroencephalographic parameter that best indicated the degree of the effect of midazolam, administered in hypnotic doses, on the central nervous system. This electroencephalographic parameter could then be used to relate midazolam plasma concentrations and electroencephalographic drug effect (pharmacodynamic modeling). Intravenous doses of midazolam (3.75 to 25 mg) were given to five men at an infusion rate of 5 mg/min. A cortical electroencephalogram was continuously recorded. Two waveform analysis approaches were examined: fast Fourier transformation and aperiodic analysis. From fast Fourier transformation and aperiodic analysis a set of parameters were examined as measures of drug effect. We conclude that the voltage per second from aperiodic analysis provided the electroencephalographic parameter that optimally measured the effect of midazolam on the central nervous system. PMID- 2225714 TI - Electroencephalographic effects of benzodiazepines. II. Pharmacodynamic modeling of the electroencephalographic effects of midazolam and diazepam. AB - The comparative pharmacodynamics of midazolam and diazepam were examined by use of the electroencephalogram as a measure of drug effect on the central nervous system. Intravenous doses of 7.5, 15, and 25 mg midazolam and 15, 30, and 50 mg diazepam were given on repeated occasions to three volunteers. Arterial plasma concentration and electroencephalogram voltage were related with nonparameteric and parametric pharmacodynamic models. The peak increases in voltage (maximal effect) and the slopes of the plasma concentration versus effect curve were similar for both drugs. The half-time of blood:brain equilibration was significantly longer for midazolam than diazepam (4.8 minutes versus 1.6 minutes). Midazolam was found to have an intrinsic steady-state potency that was approximately five times greater than that of diazepam (152 ng/ml versus 958 ng/ml). PMID- 2225715 TI - Effects of caffeine on baroreflex activity in humans. AB - The effects of caffeine or placebo on blood pressure, heart rate, and baroreflex activation (elicited by phenylephrine) were studied on young normotensive volunteers after a 7-day caffeine-free period. Subjects received oral doses of either 250 mg caffeine (n = 6) or placebo (n = 4), and hemodynamic changes were studied at 0, 30, 60, 120, and 180 minutes after drug administration. Thirty minutes after the caffeine dose, blood pressure had risen from 127 +/- 8/57 +/- 4 mm Hg to 136 +/- 3/68 +/- 5 mm Hg, heart rate was unchanged, and the baroreflex slope had decreased from 31 +/- 7 msec/mm Hg to 11.6 +/- 2 msec/mm Hg. Baroreflex sensitivity remained inhibited for the rest of the single-dose experimental period. In contrast, no significant changes were observed after either long-term caffeine ingestion in the same group or in the placebo group during the single- or multiple-dose study. These findings indicate that single but not multiple caffeine administration inhibits baroreflex activation in normotensive volunteers and this could contribute to the acute hemodynamic effects of caffeine. PMID- 2225717 TI - Extrathyroidal physiology of monoiodotyrosine in humans. AB - Normal serum monoiodotyrosine (MIT) levels (n = 152) were 0.69 +/- 0.20 nmol/l. There was wide variation of MIT levels in a 24-hour period without diurnal pattern, and there was no change throughout the menstrual cycle. MIT levels declined upon aging, but levels in hypo- and hyperthyroidism were not significantly different. MIT levels were detected in athyrotic patients (0.32 +/- 0.08 nmol/l). Desiccated thyroid raised the athyrotic MIT levels to the normal range, while levothyroxine did not. Diiodotyrosine (DIT) infusion caused an MIT rise which paralleled but lagged 1 h behind the DIT rise. These data suggest thyroidal as well as nonthyroidal sources of MIT, one of which is deiodination of DIT. Ingestion of 1 g MIT increased serum MIT to 10.6 +/- 1.7 mumol/l in women, and 7.1 +/- 2.3 mumol/l in men 30 min after ingestion; the serum half-life was 45 min. PMID- 2225716 TI - Effect of indecainide in patients with left ventricular dysfunction. AB - Indecainide, a new antiarrhythmic agent classified as type Ic was evaluated in 11 patients with heart disease who had greater than or equal to 30 ventricular premature complexes/hour, moderate-to-marked left ventricular dysfunction, and mean ejection fraction 34% +/- 8%. Patients received indecainide, 50 mg by mouth, every 6 hours and the dose was increased until greater than or equal to 80% suppression was noted, adverse effects occurred, or a maximum dose of 100 mg indecainide was given every 6 hours. Ventricular premature complexes were suppressed greater than or equal to 80% in nine patients (p less than 0.05) and ventricular tachycardia episodes were completely suppressed in five of eight patients. The effective or maximal mean daily indecainide dose was 191 +/- 32 mg; half of the responders achieved achieved efficacy at serum drug concentration greater than or equal to 600 ng/ml. Serum drug concentration was directly related to gender (r = 0.78, p less than 0.04) and inversely related to creatinine clearance (r = 0.74, p less than 0.05) and ejection fraction (r = 0.71, p less than 0.02). Indecainide prolonged mean PR and QRS intervals (p less than 0.05) but not QT or QTc. There was a linear relation between percent change in PR (r = 0.80, p less than 0.001) and QRS (r = 0.66, p less than 0.001) intervals and serum drug concentration. After starting or increasing the dose, careful observation of patients with decreased renal function or reduced ejection fraction should be exercised because they attain higher drug concentration than normal subjects. PMID- 2225718 TI - Changes in muscle proteins following different neural lesions. AB - The influence of various nerve lesions on the relative concentrations of proteins in the extensor digitorum longus (EDL), plantaris (PLN), and soleus (SOL) muscles from adult female rats was examined by electrophoresis on polyacrylamide gels. After cordotomy, levels of myosin light chains Lcs1 and -2 decreased with concomitant increases in Lcf1, -2, and -3 in SOL but not in EDL and PLN. The relative levels of several other proteins in all three muscle types were changed also. Following section of the sciatic nerve, corticospinal tract and removal of the motor cortex, the relative levels of distinct sets of protein bands in all three muscle types were altered. Only a 14,000-dalton protein band appeared to be affected by all four types of lesions. This experimental evidence supports the view that neural influences upon muscle properties are exceedingly complex. Some of these influences may be exerted via separate, central pathways to the motor neurons. PMID- 2225719 TI - Different effects of human and porcine insulin on hypoglycemia-induced abnormalities of brainstem sensory function. AB - Following a switch from porcine insulin (PI) to human insulin (HI), a subgroup of diabetic patients complained of unawareness of hypoglycemia. In the present study, a glucose clamp technique was used to assess changes in auditory evoked brainstem responses (ABR) during infusion of HI and PI (0.015 IU/kg/min) under conditions of euglycemia (about 5.00 mM) and of hypoglycemia (3.40 and 2.60 mM) in 9 healthy volunteers. Serum insulin and plasma glucose did not differ between HI and PI conditions. ABR components remained unchanged during the euglycemic clamp, but increased in latency during hypoglycemia in all subjects. At mean glucose levels of 2.60 mM, the increase in latency of ABR wave V ranged between 50 and 400 microseconds during PI infusion, and between 100 and 2,460 microseconds during HI infusion. Thus, compared to the PI condition, changes during HI infusion were significantly more variable (p less than 0.01) due to some subjects displaying extremely prolonged ABR latencies. These findings suggest that hypoglycemia induced by HI can be more detrimental to early sensory processing in humans as compared to PI. PMID- 2225720 TI - Potential mediation of prostaglandin E2 release from isolated human parietal cells by protein kinase C. AB - Parietal cells are a major source of gastric mucosal prostaglandins in various species. We examined cholinergic stimulation of prostaglandin E2 (PGE2) release from human parietal cells; using activators of the protein kinase C we attempted to get an indirect insight into cellular mechanisms which control PGE2 release. Gastric mucosal specimens were obtained at surgery and the cells were dispersed by collagenase and pronase E. Parietal cells were enriched to 65-80% by a Percoll gradient, and were incubated for 30 min. PGE2 release into the medium (radioimmunoassay) was 74-126 pg/10(6) cells/30 min under basal conditions and was 2.6-fold increased by carbachol (10(-5) and 10(-4) M). Similarly, PGE2 release was stimulated by phospholipase C (20-200 mU/ml, 364% above basal), 1 oleoyl-2-acetyl-sn-glycerol (10(-9)-10(-5) M, 229%), 12-O-tetradecanoylphorbol-13 acetate (TPA; 10(-9)-10(-5) M, 283%) and calcium ionophore A23187 (10(-7)-10(-5) M, 219%). Simultaneous presence of A23187 and TPA synergistically induced stimulation which was slightly higher than the sum of the individual responses. N (6-aminohexyl)-5-chloro-1-naphthalene sulfonamide W-7, a putative calmodulin antagonist, inhibited TPA-induced PGE2 release at concentrations regarded specific for blocking calmodulin (IC50 = 1.5 X 0(-6) M). We conclude that in human parietal cells PGE2 is released upon cholinergic stimulation and that phospholipase C and protein kinase C are involved in the control of PGE2 release. We speculate that calmodulin might interact with a protein phosphorylated by protein kinase C to cause PGE2 release. PMID- 2225721 TI - Effect of vitamin E on the oxidative state of glutathione in plasma. AB - Reduced and oxidized glutathione levels in red blood cells and plasma from humans were determined after oral vitamin E treatment. The experiments confirmed that vitamin E enhances reduced glutathione levels in red blood cells. Moreover, vitamin E supplement resulted in a significant reduction of the plasma oxidized glutathione content. Thus, it seems that the effect of vitamin E on the reduced glutathione content is not exerted via direct modulation of the glutathione synthesizing enzymes, but rather by a more general mechanism of preserving reduced glutathione consumption by reducing the burden of the glutathione system. PMID- 2225722 TI - Role of glucagon in the splanchnic and systemic hemodynamic changes induced by portal-systemic blood shunting. AB - Portal-systemic blood shunting is often accompanied by hyperglucagonemia and hemodynamic changes. To determine this causal relation, splanchnic and systemic hemodynamics (radioactive microspheres) and plasma glucagon levels (radioimmunoassay) were assessed in conditions of total portal-systemic shunting in portacaval-shunted (PCS) rats and in sham-operated (SO) normal rats. To compare these results, another hemodynamic study was undertaken basally and during glucagon infusion in nonoperated normal rats. PCS rats showed a threefold greater plasma glucagon concentration than SO animals (924 +/- 134 vs. 309 +/- 18 pg/ml, p less than 0.01), and they developed a hyperdynamic splanchnic circulation with higher portal venous inflow than SO rats (8.29 +/- 1.1 vs. 5.09 +/- 0.4 ml/min/100 g, p less than 0.05). Infusion of a pharmacological dose of glucagon in normal rats increased portal venous inflow (from 4.92 +/- 0.33 to 6.24 +/- 0.48 ml/min/100 g, p less than 0.05) so as to imply this hormone in the development of the hyperdynamic splanchnic circulation in conditions of portal systemic shunting. However, the discrepancies in systemic hemodynamics between PCS and glucagon-infused rats may be a result of the different plasma glucagon levels reached in the two groups. PMID- 2225723 TI - Is the endogenous digitalis-like factor the link between hypertension and metabolic disorders as diabetes mellitus, obesity and acromegaly? AB - Endogenous factors cross-reacting with antidigoxin antibodies have been found in several tissues and body fluids of animals and humans, using commercially available digoxin radioimmunoassay or enzyme immunoassay methods. The chemical characteristics of these endogenous factors are, at present, unknown, although it has been suggested that they could be substances with low molecular weight. Experimental studies and theoretical considerations indicate that endogenous digitalis-like factors (DDLFs), in addition to the ability to react with antibodies, might also bind to the specific cellular receptor of the cardiac glycosides and thus inhibit the membrane Na+/K(+)-ATPase (sodium pump). Therefore, EDLF can be an endogenous modulator of the membrane sodium-potassium pump and several authors have suggested that EDLF could play a role in the regulation of fluids and electrolytes, muscular tone of myocardial and also in the pathogenesis of arterial hypertension. In this review, the authors discuss the hypothesis that, in metabolic diseases such as diabetes mellitus, obesity and acromegaly, the sodium retention and volume expansion, possibly due to exaggerated sodium intake, and/or exogenously induced peripheral hyperinsulinemia and high levels of growth hormone, could trigger a sustained release of EDLF, which in turn increases the blood pressure. PMID- 2225724 TI - Diagnostic radiologists and nuclear medicine. PMID- 2225725 TI - General practice radiology--the poor relation. PMID- 2225726 TI - CT in renal and perirenal lymphoma: a further look. AB - The CT appearances of renal and perirenal lymphoma detected in 26 patients are presented. Twenty-four patients had non-Hodgkin's lymphoma and two patients Hodgkin's disease. This represented 3% of all patients scanned for routine staging of known lymphoma. Eleven patients had involvement at the time of relapse only, having had no previous evidence of renal involvement. Forty-three per-cent of all patients with renal lymphoma had no retroperitoneal lymph node involvement. Most patients had other extranodal disease at the time of presentation, most commonly bone. PMID- 2225727 TI - High resolution computed tomography of Pneumocystis carinii pneumonia in AIDS. AB - High resolution computed tomography (CT) was performed on 11 homosexual men with the Acquired Immune Deficiency Syndrome (AIDS). All had bronchoscopically proven Pneumocystis carinii pneumonia (PCP). Six patients were re-scanned following treatment and symptomatic recovery. All the scans were abnormal, most showing fine diffuse bilateral alveolar consolidation with bronchial wall thickening, despite having a normal or near-normal chest radiograph in three cases. A variety of unexpected changes such as peripheral consolidation only, upper or lower zone predominance, unilaterality, bronchial dilatation, cystic air spaces and sub pleural sparing were also seen. Following therapy, resolution of CT changes was shown to be incomplete despite clinical recovery, and whilst all the cases showed a reduction in alveolar consolidation, other findings such as new interstitial shadowing, peripheral predominance, and persistent cystic changes were observed, suggesting the healing process to be complex. Whilst the changes of PCP and its progression following treatment are well described on the plain chest radiograph, this is the first specific documentation of its appearances on narrow section CT, and its response to therapy. The usefulness of high resolution CT scanning to show early infection with PCP in the face of a normal chest radiograph is discussed, and the wide variety of CT changes occurring once the disease is established is emphasized. PMID- 2225728 TI - Chest radiographs after permanent pacing. Are they really necessary? AB - The chest radiographs of 600 consecutive patients undergoing insertion of a permanent cardiac pacemaker were reviewed to determine the incidence and nature of abnormalities present. Abnormalities were detected on the chest radiographs of 131 patients (21.8%). Unsatisfactory electrode tip position and other features related to the electrode wire were commonest (14.4%). Complications related to the lungs and pleura were present in 5.5%, and those related to the generator and pouch least frequent (1.9%). Complications occurred more frequently following installation of a replacement system (48.3%) compared to new systems (17.2%). Important complications not initially detected included pneumothorax (8/15) and poor electrode loop (26/27). Chest radiographs following permanent cardiac pacing frequently demonstrate significant abnormalities whose detection is improved by awareness of their incidence and nature. PMID- 2225729 TI - Atraumatic sternal fractures secondary to osteoporosis. AB - We describe two cases of spontaneous sternal fracture with no underlying pathology other than a severe dorsal kyphosis resulting from osteoporosis. Both patients complained of chest pain. Sternal fractures are particularly likely to occur in the elderly when the costal cartilages become ossified and there is an associated thoracic kyphosis. In elderly patients with a kyphosis the lateral thoracic radiograph should include the sternum to ensure recognition of this complication. PMID- 2225731 TI - Erosive osteoarthritis: is it a separate disease entity? AB - Erosive osteoarthritis (EOA) characteristically involves the hands of middle-aged women. The diagnosis is essentially radiological and depends upon the presence of articular surface erosions. This study investigates whether this radiological feature is a marker of a specific clinical entity. From a series of 500 consecutive patients attending a rheumatology clinic with symptomatic limb joint osteoarthritis, 24 were identified by radiological criteria to have EOA. These were age-sex matched with 24 patients from the same series who presented with osteoarthritis of the hand. Those with EOA had nearly twice as many radiographically abnormal joints in the hands as the controls (274: 144). This was almost entirely due to an increase in distal (134: 68) and proximal (79: 24) interphalangeal joint involvement, 71% of which were erosive. Erosions were found apart from the hands in both elbows of one patient with EOA. Otherwise only minor differences were present between the two groups in terms of distribution and incidence of osteoarthritic changes. There were no distinguishing serological or other clinical differences. This study has demonstrated that erosions in EOA are associated with more severe hand disease but are not apparently a marker of a separate disease entity. EOA appears to be an aggressive acute form of hand osteoarthritis and may represent the hand equivalent of similar forms of osteoarthritis in the shoulder, hip and knee. PMID- 2225730 TI - The role of discography in lumbar disc disease: a comparative study of magnetic resonance imaging and discography. AB - This study reviews prospectively a series of 29 patients who were examined by magnetic resonance imaging (MRI) and discography for degenerative disc disease. All had persistent low-back pain and non-diagnostic initial investigations, including plain films, myelography and/or computed tomography (CT). The imaging characteristics for degenerative disc disease correlated in 65 out of 73 intervertebral levels. All symptomatic discs were degenerate on both MRI and discography. Features of degenerative disc disease on MRI were assessed retrospectively, with a view to identifying the symptomatic level as defined by discography. MRI could not reliably detect this level, particularly in those with multi-level degenerative disc disease. Positive reproduction of symptoms at discography was the criteria used for surgery. All 12 patients in this group had posterior spinal fusion performed. Nine improved and three were unchanged. Of the ancillary features associated with disc degeneration, only a bulging annulus fibrosis proved to be of any value on MRI. Nonetheless, MRI should be used as the primary investigation in this patient group as it can lead to a marked reduction in the number of disc levels requiring injection. PMID- 2225732 TI - Magnetic resonance imaging in extranodal pelvic lymphoma. AB - A practical MRI strategy for the investigation of pelvic pain in patients with suspected recurrent lymphoma is described and illustrated in five patients. A T1 weighted sagittal examination of the lumbo-sacral spine is used to examine the vertebral bone marrow, spinal canal, exit foraminae and para-aortic lymph nodes. T2-weighted and balanced images are obtained in the axial plane through the pelvis. The balanced images give an excellent demonstration of pelvic lymph nodes and the T2-weighted images are sensitive to the presence of abnormal soft tissue masses and marrow disease. PMID- 2225733 TI - Fibrinolytic therapy for infra-inguinal synthetic graft occlusions. AB - The results of infra-inguinal graft fibrinolysis are variable, and the true success rates are frequently disguised by the inclusion of patients receiving adjunctive surgery, such as surgical thrombectomy, anastomosis revision and graft extension. Follow-up is sparse. As part of a larger prospective study, we have offered fibrinolysis using streptokinase to 10 patients with occluded infra inguinal synthetic grafts. In one patient the graft could not be entered with a catheter. The remaining nine patients received local low-dose intra-arterial streptokinase. Six patients experienced complete lysis and were discharged with functioning grafts. Significant stenoses were dilated by transluminal angioplasty. The median graft patency duration was 7 months. Two patients have since required above-knee amputations. Our results using transluminal angioplasty are comparable to those results where adjunctive surgery has been used to treat underlying anastomotic stenoses. Further research into graft anastomotic stenosis management is indicated. PMID- 2225734 TI - Oesophageal stenosis distal to oesophageal atresia. AB - Oesophageal atresia with or without tracheo-oesophageal fistula is often associated with a functionally abnormal distal oesophagus. The association of oesophageal atresia and a distal oesophageal stenosis is less well recognized and is usually regarded as a rarity. We describe four cases of oesophageal stenosis distal to oesophageal atresia and review the literature relating to this condition. PMID- 2225735 TI - The complications of high brachial artery puncture. AB - Fifty-two angiograms via a high brachial puncture were performed in Sheffield from 1986 to 1988 in patients in whom femoral artery catheterization was not possible or was contraindicated. Follow-up was obtained in 49 procedures. The procedure was initially successful in 43 cases. Twelve patients developed haematomas, graded large in 5, but no intervention for haematoma was required. The radial pulse was diminished or absent at the end of examination in four patients; three of these patients had no associated ischaemia, the pulse returning spontaneously within 24 hours, although remaining chronically reduced in one patient. One patient developed ischaemia due to acute occlusion of the brachial artery--this was successfully treated with immediate angioplasty. Paraesthesiae in the median nerve distribution were noted in two patients. These resolved spontaneously and no permanent neurological problem was seen. We conclude that high brachial artery puncture is a useful alternative when femoral artery puncture is not possible. PMID- 2225736 TI - Cholesterol embolization following angiography. AB - A case of cholesterol embolism following mesenteric angiography is reported. Although usually associated with a difficult study in atheromatous vessels this lethal complication occurred in an otherwise uncomplicated examination. This serves as a reminder of the attendant hazards of vascular studies in such patients and emphasizes the need for a careful technique to minimize any vessel wall trauma. PMID- 2225737 TI - Subcutaneous herniation of gall-bladder with spontaneous cholecystocutaneous fistula. AB - Spontaneous cholecystocutaneous fistula is now a clinical rarity due to improvements in the treatment of biliary tract diseases. This case report describes a 67-year-old woman in whom subcutaneous herniation of a pathologically dilated gall-bladder was followed by spontaneous discharge of pus and mucus with formation of a cholecystocutaneous fistula. The use of serial computed tomography examinations enabled this unusual diagnosis to be made. PMID- 2225738 TI - Uterine metastasis from stomach cancer: radiological findings. AB - The uterus is an unusual site for metastasis from an extrapelvic neoplasm. We report a case of uterine metastasis with extensive calcification. Plain radiography, ultrasonography and CT showed diffuse calcification within the uterine wall and T2-weighted MR images showed abnormally high signal intensity of the entire myometrium. PMID- 2225739 TI - Tuberculous dactylitis in childhood. The need for continued vigilance. AB - A case of tuberculous dactylitis in a 3-year-old Chinese boy is presented and the radiographic findings and differential diagnosis discussed. Although this is a rare condition, the diagnosis should be considered when a member of the immigrant community presents with an unusual bony lesion. PMID- 2225740 TI - Solitary plasmacytoma of the frontal bone. AB - We report a case of a solitary, painless, lytic lesion in the frontal bone in an otherwise asymptomatic patient. This was investigated with plain radiographs, computed tomography (CT), angiography and finally biopsy. Histology showed it to be a plasmacytoma. The radiological features of this lesion are discussed. Solitary plasmacytoma of bone has an uncertain relationship to multiple myeloma; it has only rarely been described in the skull and very rarely in the frontal bone. PMID- 2225741 TI - Delayed cardiac tamponade following NDA. PMID- 2225742 TI - The basic radiology system. PMID- 2225743 TI - Children with urinary tract infection. PMID- 2225744 TI - The telephone: servant or tyrant? You decide. PMID- 2225745 TI - Spinal cord injuries cost Colorado $8 million per year. PMID- 2225747 TI - Panel reviews therapy for early breast cancer; explicit advice on adjuvant therapy lacking. PMID- 2225748 TI - Levamisole approved for use in adjuvant regimen for colon cancer. PMID- 2225749 TI - New class I antiarrhythmic, moricizine, approved by FDA. PMID- 2225750 TI - Red-neck syndrome associated with intraperitoneal vancomycin. PMID- 2225751 TI - Comparison of two microcomputer Bayesian pharmacokinetic programs for predicting serum gentamicin concentrations. PMID- 2225752 TI - Vancomycin pharmacokinetics in infants undergoing extracorporeal membrane oxygenation. PMID- 2225753 TI - Discovery of the gene defect in cystic fibrosis: implications for diagnosis and treatment. PMID- 2225754 TI - Criteria for use of intravenous vancomycin for treatment of infections. PMID- 2225755 TI - Processing distinctions between stems and affixes: evidence from a non-fluent aphasic patient. AB - In this paper, we study the ability of a non-fluent aphasic patient, BN, to comprehend morphologically complex words when they appear in utterance contexts. We first establish that he is insensitive to the contextual appropriateness of both derived and inflected words. In a further experiment we show that he has no difficulty processing the stems of complex words and conclude that his problem is with the bound morphemes themselves. We then ask whether this problem is due to his inability to access either the phonological form of a morphologically complex word or its semantic and/or syntactic content. We find that only the access of semantic and syntactic content is impaired. We conclude from these six studies that: (a) BN presents a counter-example to the claim that non-fluent patients have particular difficulty with those aspects of morphology which have a syntactic function; (b) BN processes both derived and inflected words by mapping the sensory input onto the entire full-form of a complex word, but the semantic and syntactic content of the stem alone is accessed and integrated into the context. The semantic and syntactic implications of the suffix are never evaluated. This implies separate representation of the stems and suffixes of some types of morphologically complex words. PMID- 2225756 TI - Children's understanding of counting. AB - This study examines the abstractness of children's mental representation of counting, and their understanding that the last number word used in a count tells how many items there are (the cardinal word principle). In the first experiment, twenty-four 2- and 3-year-olds counted objects, actions, and sounds. Children counted objects best, but most showed some ability to generalize their counting to actions and sounds, suggesting that at a very young age, children begin to develop an abstract, generalizable mental representation of the counting routine. However, when asked "how many" following counting, only older children (mean age 3.6) gave the last number word used in the count a majority of the time, suggesting that the younger children did not understand the cardinal word principle. In the second experiment (the "give-a-number" task), the same children were asked to give a puppet one, two, three, five, and six items from a pile. The older children counted the items, showing a clear understanding of the cardinal word principle. The younger children succeeded only at giving one and sometimes two items, and never used counting to solve the task. A comparison of individual children's performance across the "how-many" and "give-a-number" tasks shows strong within-child consistency, indicating that children learn the cardinal word principle at roughly 3 1/2 years of age. In the third experiment, 18 2- and 3 year-olds were asked several times for one, two, three, five, and six items, to determine the largest numerosity at which each child could succeed consistently. Results indicate that children learn the meanings of smaller number words before larger ones within their counting range, up to the number three or four. They then learn the cardinal word principle at roughly 3 1/2 years of age, and perform a general induction over this knowledge to acquire the meanings of all the number words within their counting range. PMID- 2225757 TI - Numerical abstraction by human infants. AB - Across several experiments, 6- to 8-month-old human infants were found to detect numerical correspondences between sets of entities presented in different sensory modalities and bearing no natural relation to one another. At the basis of this ability, we argue, is a sensitivity to numerosity, an abstract property of collections of objects and events. Our findings provide evidence that the emergence of the earliest numerical abilities does not depend upon the development of language or complex actions, or upon cultural experience with number. PMID- 2225759 TI - Acoustic signaling in the black rat (Rattus rattus). AB - This study surveyed the vocalization repertoire of descendants of wild-trapped Rattus rattus. Sound recordings synchronized with behavioral observations were conducted in an animal colony living undisturbed under seminatural conditions. Analyses of sound recordings revealed 10 distinct acoustic signals, 5 of which were in the ultrasonic frequency range. The time course and the frequency pattern of the analyzed sounds were similar to those described for R. norvegicus, and they occurred in comparable situations. A species-specific difference may be the intensity of the emitted sounds. The possible communicative function of the acoustic signals is discussed. PMID- 2225758 TI - Inferences about guessing and knowing by chimpanzees (Pan troglodytes). AB - The visual perspective-taking ability of 4 chimpanzees (Pan troglodytes) was investigated. The subjects chose between information about the location of hidden food provided by 2 experimenters who randomly alternated between two roles (the guesser and the knower). The knower baited 1 of 4 obscured cups so that the subjects could watch the process but could not see which of the cups contained the reward. The guesser waited outside the room until the food was hidden. Finally, the knower pointed to the correct cup while the guesser pointed to an incorrect one. The chimpanzees quickly learned to respond to the knower. They also showed transfer to a novel variation of the task, in which the guesser remained inside the room and covered his head while the knower stood next to him and watched a third experimenter bait the cups. The results are consistent with the hypothesis that chimpanzees are capable of modeling the visual perspectives of others. PMID- 2225760 TI - Social transmission of food preferences in Japanese monkeys (Macaca fuscata) after mere exposure or aversion training. AB - In Experiment 1, 3 mother-child pairs of Japanese monkeys (Macaca fuscata) were given simultaneous choice tests between raisins and popcorn. The mothers and offspring showed different choice patterns. Cofeeding opportunities were then alternated with individual choice tests. In Experiment 2,2 other pairs were added. Each animal was again offered simultaneous choice tests between marshmallows and almonds. Food aversion conditioning was used to create different choice patterns for mothers and offspring. After cofeeding and choice tests, the differences in choice patterns disappeared in both experiments. The changes after contact with the other's eating pattern during cofeeding was as follows: foods consumed by either came to be eaten by both; foods consumed by both continued to be eaten by both; and foods consumed by neither continued to be ignored. The results provide evidence for social transmission of food preferences in this species. PMID- 2225761 TI - Number-related discrimination and summation by squirrel monkeys (Saimiri sciureus sciureus and S. boliviensus boliviensus) on the basis of the number of sides of polygons. AB - In Experiment 1, with the number of sides or angles of irregular polygons as cues, programmed training, and a 90% correct criterion (36 of 40), 2 squirrel monkeys' (Saimiri sciureus sciureus and S. boliviensus boliviensus) best performances were to discriminate heptagons from octagons, a 3rd's best was hexagons from heptagons, and a 4th's best was pentagons from heptagons. In Experiment 2, on most trials 2 polygons on one or both discriminanda had to be summed to determine which discrimination had the total fewer sides. Only 1 monkey met criterion (27 of 30) on the 2 tasks, 6 vs. 8 and 7 vs. 8 sides, but the other 3 performed better than chance on the 6 vs. 8 task. We conclude that previous studies of animals' discrimination of polygons in terms of complexity were minimally relevant to this work, and counting and subitizing were rejected in favor of a prototype-matching process to explain our monkeys' performances. PMID- 2225762 TI - Geometric modules in animals' spatial representations: a test with chicks (Gallus gallus domesticus). AB - Recent work has shown that in place-finding tasks rats rely on the geometric relations between the goal object and the shape of the environment. We tested young chickens (Gallus gallus domesticus) on similar tasks in a reference memory paradigm to determine whether differences exist between species in the ability to use geometric and nongeometric spatial information. The main findings were that chicks: (a) encoded and used both geometric and nongeometric (featural) information; (b) did not use the overall spatial arrangement of the features; (c) relied primarily on nongeometric cues when faced with contradictory information. Two mechanisms are evident in chicks' spatial representations: a metric frame for encoding the spatial arrangement of surfaces as surfaces and a cue-guidance system for encoding conspicuous landmarks near the target. The possibility of hierarchical organization and species differences in these two mechanisms are discussed. PMID- 2225763 TI - Changes in mating vocalizations over the ejaculatory series in rats (Rattus norvegicus). AB - Rats (Rattus norvegicus) produce ultrasonic calls during mating. We examined changes in the structure and pattern of such vocalizations over the ejaculatory series. In Experiment 1, vocalizations were recorded from 11 pairs of rats through 3 ejaculatory series and analyzed spectrographically. We classified 4 categories of call by spectral frequency and duration. Calls of low frequency, long duration, and high intensity occurred more often shortly before the ejaculation and were associated with mounting without intromission, a behavior that often occurs shortly before ejaculation. The high-frequency calls did not vary in number across the series. In Experiment 2, vocalizations were recorded from males paired with devocalized females. Males produced all vocalization patterns produced by pairs in Experiment 1. Results suggest that most pre ejaculatory calls are produced by males and may potentially affect female sexual behavior. PMID- 2225765 TI - Differences in affiliative behavior, pair bonding, and vaginal cytology in two species of vole (Microtus ochrogaster and M. montanus). AB - Prairie voles (Microtus ochrogaster) and montane voles (M. montanus) display marked differences in social organization in the field. Trios of 1 male and 2 females were studied in a large enclosure for a 10-day period. Prairie voles spent 59% of the observation time in side-by-side contact, whereas montane voles spent only 7% of the time in contact. Vaginal smears indicated female-female suppression of estrus in prairie voles; female montane voles appeared to cycle in the presence of males. Male prairie voles preferentially paired and nested with 1 of the females, and vaginal estrus generally followed pair formation by 2 days. Male montane voles did not spend time preferentially with either female, even after mating. These results suggest that the contrasting mating systems of these species result from differences in the propensity for affiliative behavior and social bonding rather than from mate availability or female receptivity. PMID- 2225764 TI - An unusual pattern of copulatory behavior in a South American cricetid rodent: Akodon molinae. AB - We describe the copulatory behavior and the morphology of the male genital tract of a member of a tribe (Akodontini) for which no information on copulatory behavior has been available. Copulation in Akodon molinae is characterized by multiple intromissions with no intravaginal thrusting, a single ejaculation, and a brief lock with the deposit of a plug. This pattern is unusual because of the combination of locking with both multiple intromissions and plugs. The latter combination, and similar standard measures of copulatory behavior, have been reported for Acomys cahirinus, a murid that frequently shows more than 1 ejaculation. Also, the standard measures of copulation in A. molinae resemble those of Calomys callosus, another South American cricetid, which shows intravaginal thrusting and infrequent locks. The functional significance and the anatomical correlates of locking and plug deposition in this species are discussed. PMID- 2225766 TI - Hand preference and performance on unimanual and bimanual tasks in capuchin monkeys (Cebus apella). AB - Patterns of manual preference and the extent to which preference provided a benefit in performance (movement time) were evaluated in 7 young adult capuchin monkeys (Cebus apella). Directions of preference were inconsistent within individual animals across home-cage activities, unimanual, and bimanual experimental tasks. Preferences were more strongly expressed in the experimental tasks than in the home cage. A left bias in the population for prehension, predicted by recent theories, was not evident in any setting. Movement time was moderately negatively correlated with degree of preference within experimental tasks. The benefit to performance conferred by lateral preference was not dependent on whether the right or left hand was preferred. Lateralization of prehension appears to be a flexible process in these monkeys, which can result in quickly realized benefits in some conditions. PMID- 2225767 TI - Light-dark variation and changes across the lactational period in the behaviors of undisturbed mother and infant guinea pigs (Cavia porcellus). AB - Lactating guinea pigs (Cavia porcellus) and their litters were observed by videophotography across the light/dark cycle at 1, 11, 21, and 31 days postpartum. The highest level of behavioral activity was seen in the dark, particularly in the hour after light offset. This circadian pattern was evident from Day 1 in mothers and from Day 11 in pups. Contact between mothers and pups was inversely related to activity, occurring more frequently during light. Maternal grooming of pups occurred on Day 1 and then declined: self-grooming by pups increased across days. Intake of solid food and water by pups occurred on Day 1 and increased thereafter. A nearly complete transition from nursing to independent ingestion was observed between 21-31 days of age. Overall, we document several ontogenetic changes in young guinea pigs and demonstrate that under laboratory conditions mother and infant guinea pigs exhibit a nocturnal activity pattern. PMID- 2225769 TI - Paramyosin and the catch mechanism. AB - 1. Catch is a mechanism found in many molluscan smooth muscles in which tension is maintained at relatively low energy cost. 2. Paramyosin forms the core of thick filaments. In catch muscle paramyosin concentrations are high and the thick filaments are relatively long. 3. The mechanism of catch is not understood, but the consensus is that tension during catch is borne by slowly-cycling cross bridge attachments to actin. 4. Stimulation by acetylcholine increases intracellular Ca2+ and initiates a contraction characterized by a relatively rapid cross-bridge cycling. Reduction of Ca2+ can lead to relaxation or catch. Relaxation occurs only when a second neurotransmitter, serotonin, is present. 5. The catch state is released by serotonin, via activation of adenylate cyclase, increased levels of cAMP and phosphorylation of one or more contractile proteins, possibly paramyosin. Other targets for phosphorylation are discussed. 6. The contractile cycle of catch muscles, therefore, is controlled by both Ca2+ and cAMP. PMID- 2225768 TI - The HSP70 multigene family of Caenorhabditis elegans. AB - 1. The heat shock response of the nematode Caenorhabditis elegans has been characterized. 2. There are at least nine genes in the hsp70 multigene family of C. elegans. 3. Five of the hsp70 genes have been characterized and assigned to one of at least three hsp70 gene subfamilies. One of the subfamilies consists of an hsp70 protein that has the potential to be translocated into the endoplasmic reticulum and another subfamily consists of a protein that has the potential to be translocated into the mitochondria. 4. The C. elegans hsp70 multigene family has several unique characteristics including introns in the heat inducible hsp70 genes, at least one trans-spliced hsp70 mRNA and two grp78 related genes, one of which is highly heat inducible. 5. The identification and characterization of C. elegans hsp70 multigene family is the basis for a genetic characterization of the regulation and function of a gene family during the development of a multicellular eukaryote. PMID- 2225770 TI - Phosphorus nuclear magnetic resonance of diverse phosvitin species. AB - 1. High resolution 31P nuclear magnetic resonance (NMR) spectra, with and without proton decoupling, of the principal egg phosphoproteins--phosvitins--of a bird (Gallus gallus), an amphibian (Xenopus laevis) and a fish (Salmo gairdneri) were obtained. 2. The spectra were evaluated with special reference to available amino acid sequences and the major NMR resonance in all three spectra was assigned to phosphoserine clusters. 3. The resolution of numerous additional phosphorus resonances provides the basis for further investigation of the particular molecular environments of phosvitin-bound phosphoryl groups and their involvement in the diverse binding modes for metal complex formation by phosvitins. PMID- 2225771 TI - Hepatic alcohol dehydrogenase activity in chick hepatocytes towards the major alcohols present in commercial alcoholic beverages: comparison with activities in rat and human liver. AB - We have compared hepatic alcohol dehydrogenase activities in chick, rat and human liver with the major alcohols in commercial alcoholic beverages. 1. Chick and rat hepatic alcohol dehydrogenase was greater when assayed at a physiological pH in buffer containing chloride ions, as compared with the activity in pyrophosphate buffer at alkaline pH. 2. In contrast to reports of instability of ADH to freezing, we found the enzyme from all three species stable to freezing in 0.25 M sucrose. 3. Rat liver enzymatic activity was unstable in the presence of substrate, where as that of chick and human was not. 4. For all three species, the Km of hepatic ADH for substrate decreased with increasing chain length of alcohols. In both chick and human samples, the Vmax values for the higher chain alcohols were similar to that with ethanol, while in rat samples, ADH activity was dramatically lower with the higher chain alcohols compared to ethanol. PMID- 2225773 TI - Comparison of delta-aminolaevulinic acid dehydratase activity in chick liver during sex steroid hormone dependent primary and secondary stimulation. AB - 1. Comparative study on primary and secondary stimulation of hepatic delta aminolaevulinic acid dehydratase (ALAD) (EC 4.2.1.24) was carried out after oestradiol-17 beta and/or testosterone administration in immature female chicken. 2. When 2 mg/day oestradiol was administered to birds for 15 days successively, hepatic total ALAD activity increased to 170% by day 15 of primary stimulation, whereas a more rapid increased rate was observed within day 3 of secondary stimulation and thereafter the hepatic ALAD activity maintained the same high level from day 3 to day 15. 3. Testosterone (2 mg/day) alone decreased hepatic total ALAD activity during both primary and secondary stimulation. 4. When testosterone (0.25-10 mg/day) was injected into birds in combination with 2 mg oestradiol for 15 days during primary and secondary stimulation, only an antagonistic effect of testosterone on oestradiol-stimulated total ALAD activity in liver was observed independently of the testosterone amount administered. However, the extent of suppression of hepatic ALAD activity by testosterone during primary stimulation was markedly different from that of secondary stimulation. PMID- 2225772 TI - Comparative study of lens proteins of gray squirrel and human. AB - 1. The four crystallins of the gray squirrel lens have been characterized using gel filtration chromatography, polyacrylamide gel electrophoresis, and immunoblotting. Alpha, beta-heavy, beta-light, and gamma crystallins of squirrel lenses have been identified immunologically, and they cross-react strongly with rabbit polyclonal antibodies. The gamma-24 crystallin of the squirrel lens also reacts strongly with monoclonal anti-human lens gamma-24, as shown by its inhibition of the ELISA reaction by 85%. 2. The water-insoluble urea soluble proteins represent non-covalently associated species of soluble crystallins and the lens cytoskeletal proteins. The membrane intrinsic protein in the urea insoluble pellet has a mol. wt of 27,000 but other lower and higher mol. wt components are also present, which were removed by washing with 0.1 NaOH. The N terminal 30 amino acid of squirrel lens gamma crystallin was found to be identical to that of the bovine (and human) lens. 3. Measurements of the distribution and state of SH and SS compounds in the squirrel lens have shown greater similarities to those of primates than those of rodents. The findings show that on the basis of both protein and sulfur chemistry the squirrel lens is a representative model for studies of oxidative lens changes in diurnal animals, including man. PMID- 2225774 TI - Mouse mammary carcinoma delta-aminolevulinate dehydratase. AB - 1. Aminolevulinate dehydratase (ALA-D) was studied in crude extract from mouse mammary carcinoma, normal mouse liver and tumour bearing mouse liver. 2. A Michaelis-Menten behaviour and Km values between 0.24 and 0.31 mM were obtained for the enzyme in either source. 3. In all three tissues there was a linear relationship between porphobilinogen formation and incubation time, up to 120 min, ALA-D was thermostable and optimum pH was at 6.8. 4. There seems to be no structural alterations in tumoural ALA-D as compared with the enzyme from liver of both normal and tumour bearing mice. PMID- 2225775 TI - A comparative study of alkaline phosphatases among human placenta, bovine milk, hepatopancreases of shrimp Penaeus monodon (Crustacea: Decapoda) and clam Meretrix lusoria (Bivalvia: Veneidae): to obtain an alkaline phosphatase with improved characteristics as a reporter. AB - 1. Alkaline phosphatases were purified from human placenta, bovine milk, shrimp and clam with a final spec. act. of 67,000, 32,000, 22,000 and 15,000 U/mg of protein respectively. 2. The alkaline phosphatase from Meretrix lusoria is unique with its thermostability at 65 degrees C for 30 min; whereas the remaining enzymes studied, including the human placental alkaline phosphatase, are inactivated and have negligible activities. 3. The alkaline phosphatase from Penaeus monodon can be differentiated by its pH optimum at 9.0; the remaining enzymes studied have their optimal pH at 10.0. 4. The alkaline phosphatases from shrimp and clam are proposed to be applied as "reporters" in the study of mammalian cells. PMID- 2225776 TI - Sterols in the plasma and digestive gland-gonad complex of Biomphalaria glabrata snails, fed lettuce versus hen's egg yolk, as determined by GLC. AB - 1. Gas-liquid chromatography studies were done on sterols in plasma and the digestive gland-gonad (DGG) complex of Biomphalaria glabrata snails fed lettuce vs hen's egg yolk. 2. The major sterols present in the DGG of both populations were cholesterol, stigmasterol, beta-sitosterol, campesterol, and desmosterol. 3. The percentage composition of cholesterol in the DGG of yolk vs lettuce fed snails was 82 and 51, respectively. 4. The elution profiles of sterols in the plasma of yolk vs lettuce fed snails were similar; both contained desmosterol, campesterol, and stigmasterol, negligible amounts of cholesterol, and unidentified sterols. 5. The high lipid diet increased the level of cholesterol in the DGG but not in the plasma. PMID- 2225777 TI - A comparative study of glycosylated haemoglobin level in the Arabian camel (Camelus dromedarius) during different seasons. AB - 1. The extent of haemoglobin glycosylation from 60 camels has been determined (4.39%) in blood samples drawn during winter. 2. Phosphate (9.45 mg/dl), DPG (2.9 mumol/ml) and glucose (138 mg/dl) levels were also recorded. 3. In addition the P50 at pH 7.4 was measured (22.8 Torrs). 4. The data obtained compared with human blood levels and with levels reported for camels during summer sampling. 5. Despite the fact that camels have higher blood glucose levels than humans, the extent of glycosylation is much less in camel blood than in human blood. PMID- 2225778 TI - A CPU benchmark for protein crystallographic refinement. AB - The CPU time required to complete a cycle of restrained least-squares refinement of a protein structure from X-ray crystallographic data using the FORTRAN codes PROTIN and PROLSQ are reported for 48 different processors, ranging from single user workstations to supercomputers. Sequential, vector, VLIW, multiprocessor, and RISC hardware architectures are compared using both a small and a large protein structure. Representative compile times for each hardware type are also given, and the improvement in run-time when coding for a specific hardware architecture considered. The benchmarks involve scalar integer and vector floating point arithmetic and are representative of the calculations performed in many scientific disciplines. PMID- 2225779 TI - A computer program in BASIC for calculating gradients used in chromatography, electrophoresis and centrifugation. AB - Concentration gradients are often used in separations based on chromatographic, electrophoretic and centrifugal methods. In this report, a BASIC computer program for calculating and graphically representing gradients is described. This GRADIENT program is intended to be run on IBM-compatible computers. PMID- 2225780 TI - An algorithm for the computer calculation of the coefficients of a polynomial that allows determination of isoelectric points of proteins and other macromolecules. AB - The isoelectric point (pI) of a macromolecule containing any number of acid-base residues can be expressed as a polynomial whose coefficients are related to both the number of acid-base residues present in the molecule and their K values. Polynomials of degree higher than 5 are too complicated to be solved manually. An algorithm is here presented which allows, with few sentences written in BASIC, the calculation of the polynomial coefficients. With this knowledge and using standard polynomial solving programs, the isoelectric point of the macromolecule can be calculated. PMID- 2225781 TI - Automatic chart reader--an example of computer systems for patients' data interpretation. AB - A new approach to the processing of circular medical charts based on "odd symmetry digital subtraction" is presented. The technique allows automatic digitisation of these charts using an image processing system based on a flat bed scanner. This approach is simple, fast, and reliable; and provides a system in which the digitised image is processed by a microcomputer to extract and quantify the plotted information. The main features and the potential applications of this approach in medical and nonmedical fields are discussed. PMID- 2225782 TI - A computerized bioelectrical cardiac monitor. AB - The use of a micro-computer improves the performance of an impedance cardiograph. The impedance signals and the ECG are real-time processed and four analog signals are displayed on the screen. A beat-to-beat estimation of cardiac output and several indexes are computed and displayed. User's interface is by interactive screen menus. Some facilities permit data identification, storage and post processing. The software has been designed in such a way as to be adaptable to each specific application and to enable the development of new routines for cardiac signal processing. The signals recorded in healthy patients are in agreement with the results of other similar studies. PMID- 2225783 TI - A provider-interactive medical record system can favorably influence costs and quality of medical care. AB - The Geriatric Record and Multidisciplinary Planning System (GRAMPS) is a provider interactive computerized medical record system designed to support outpatient geriatric practice in Department of Veterans Affairs (DVA) clinics. In a controlled prospective study, physician use of the system was demonstrated to be associated with a reduction of the costs, and improvement in the quality and outcomes of patient care. The system was well-accepted by users, and provided a practical approach to physician data-entry. The system's text-handling and narrative generation capabilities support an extensive clinical content domain, contributing to overall performance. These features will be described in detail. PMID- 2225784 TI - Design of the diagnostic encyclopedia workstation (DEW). AB - The Diagnostic Encyclopedia Workstation (DEW) contains reference knowledge for diagnostic support in pathology. Illustrations are accessible via a video disc device. DEW can hold more knowledge, pictures and case histories than books, and its information is accessible via several entries. Software for data entry has been written in MUMPS with use of the relational database toolkit AIDA, which is particularly suited for manipulation of free text. The graphical mouse-driven user interface is written in C using MetaWindows. The DEW contains 85 diagnoses in ovarian pathology, covering all frequent cases and many rarities, illustrated by approximately 3000 pictures, divided among 158 cases. PMID- 2225785 TI - Comments on "Respiratory waveform pattern recognition using digital techniques". PMID- 2225787 TI - SAPHIRE--an information retrieval system featuring concept matching, automatic indexing, probabilistic retrieval, and hierarchical relationships. AB - SAPHIRE (Semantic and Probabilistic Heuristic Information Retrieval Environment) is an experimental computer program designed to test new techniques in automated information retrieval in the biomedical domain. A main feature of the program is a concept-finding algorithm that processes free text to find canonical concepts. The algorithm is designed to handle a wide variety of synonyms and convert them to canonical form. This allows natural language to be used for query input and also serves as the basis for a new approach to automatic indexing based on a combination of probabilistic and linguistic methods. PMID- 2225786 TI - Automatic geometrical registration of fluorescein retinal angiograms. AB - Changes in retinal microvascular perfusion revealed by fluorescein angiography have been reported in patients undergoing coronary artery surgery. Quantification of these changes is important and current techniques depend on careful visual inspection of the angiograms by humans. Computer image processing methods can be used to identify and highlight differences, but geometrical registration of the images is a prerequisite to the comparisons. Automatic methods for locating and matching reference points have therefore been developed. In combination with an iterative process which used least-squares error to calculate the transformation coefficients, subsets of reference points were selected and used to register successfully 20 image pairs. PMID- 2225788 TI - A programming language and a system for automated time- and laboratory test level dependent decision-making during patient monitoring. AB - A programming language specifically designed for automated time-dependent decision-making during patient monitoring (obtaining test requests, scheduling of test requests, cancelling of test requests, the issuing of messages to clinician or laboratory) has been developed. The output from a program written in this language is a set of decision rules in tabular form (a patient type), intended to solve a specific problem related to patient monitoring. A system for automated decision-making based on this language utilizes a file of patient types and a patient file. Whenever a new patient record is created, the patient's type is defined and the corresponding patient type is copied from the patient type file and linked to the patient's record. The system is activated, i.e., the decision rules are implemented and the tables of the patient's type updated, when laboratory results are available, when a clinician wants to order tests, and at regular user-defined intervals. PMID- 2225789 TI - A method for conforming the pH dependence of the michaelis parameters of nonallosteric enzymes to four kinetic schemes. AB - A nonlinear regression program for the analysis of the effect of pH on enzyme activity has been developed for the IBM micro range and compatible machines. The program conforms the V and Km pH profiles to one of four commonly occurring kinetic schemes. By using multiple linear regression the program computes initial estimates for the nonlinear search which are thus not required from the user. Two nonlinear optimization methods are included in order to effectively handle the nonnegativity constraints on the parameters. The program is user-friendly and provides plots of the fit and residual plots to help the user decide on the goodness of fit obtained. The program was coded in Turbo Pascal version 4.0 and runs on IBM micros or close compatibles with four types of graphics cards. PMID- 2225790 TI - Conducting a matched-pairs historical cohort study with a computer-based ambulatory medical record system. AB - We describe techniques for using the Computer-Stored Ambulatory Record (COSTAR) at the Massachusetts General Hospital to conduct a historical cohort study of the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on blood pressure control. A query language was used to identify patients satisfying clinical and data-availability criteria, to match these patients with clinically similar patients not exposed to NSAIDs, and to collect data from the COSTAR records of both groups of patients to determine any differences in outcome. We analyzed over 30,000 patient records to select 90 pairs of patients used in the study. This approach to clinical research uses data collected for purpose of patient care and so does not require the separate recording of patient data for clinical research. Using computer-based medical record systems with a query language allows selection and matching of patients using detailed demographic and clinical criteria. The ability to conduct such studies is an advantage of computer-based medical record systems over the paper record system. PMID- 2225791 TI - Frequency-domain digital filtering techniques for the removal of powerline noise with application to the electrocardiogram. AB - This paper presents two new local processing frequency-domain methods for the removal of powerline noise from electrophysiological signals. The first is based on an iterative division or a multiplication of a set of frequencies centered at 60 Hz. The second users a basic property of the natural logarithm to smooth the 60-Hz noise. Both methods are intended to reduce powerline noise without affecting the frequency spectrum of the signal in the regions surrounding 60 Hz. For illustration, these local processing methods are applied to artificial and real electrocardiographic (ECG) data and are compared to a fixed IIR notch digital filter which is designed by pole-zero placements on the unit circle. The performance of each method is measured by the error squared, which is the square of the difference between the original noise-free signal and the filtered noisy ECG. Finally, since the two methods are iterative processes, comparison of their rate of convergence to a predefined noise reduction level is considered. PMID- 2225792 TI - Determination of first and second derivatives of progress curves in the case of unknown experimental error. AB - The first and second derivatives of progress curves are obtained from the cubic spline function. The new approach is based on a development of the splining quality test which was used for estimating the precision of the splining. The proposed method is used on a computer with a FORTRAN 77 program. The method may also be applied for an approximate estimation of experimental error. PMID- 2225793 TI - Two BF*F subtypes found by isoelectric focusing have restricted distributions in the Finnish MHC haplotypes. AB - The factor B (BF) polymorphism revealed by immunofixation of plasma samples is made up of more than 20 variants, of which 2 variants are common, S and F, 2 less common, F1 and S07, and the rest of the variants are very rare. In this work we have adapted a rapid method to subdivide the BF*F allele into *FA and *FB by IEF in nontoxic agarose gel. The FA subtype manifested as two major bands and FB as one band both in native and desialylated samples. *F1, *S and *S07 were shown as monomorphic proteins, but differ in their sensitivities to degradation caused by neuraminidase treatment. *FA and *FB showed restricted distributions among the HLA haplotypes of the homogenous Caucasoid Finnish population. *FA was positively associated with the haplotypes Cw3,Bw62,C4A3BQ0 (or A3B1) and *FB with the haplotypes A3,Cw4,B35,DR1,C4A3BQ0 (or A2BQ0, A3,2BQ0). PMID- 2225794 TI - Elutable factors from latex-containing materials activate complement and inhibit cell proliferation. An in vitro biocompatibility study of medical devices. AB - Eluates from one all-silicone and two different combined silicone-latex catheters and one latex and one vinyl procedure glove were mixed with normal human serum and tested in a C3 complement activation assay. Simultaneously the eluates were tested in a cellular assay to measure inhibition of cellular proliferation. The combined silicone-latex catheters and the latex procedure glove caused a pronounced complement activation and inhibited cell proliferation. However, the response ranging was opposite in the two assays, suggesting that different soluble factors were responsible for the observed reactions. No complement activation or inhibition of cellular proliferation was observed for the all silicone catheter and the vinyl procedure glove. Our results demonstrate that different assays should be taken into account when biocompatibility is evaluated. PMID- 2225795 TI - Study of genetic polymorphism of seventh complement component in two families with hereditary deficit. AB - The results of an allelic segregation of C6 and C7 were studied in two Spanish families that have members with C7 deficiency. Absence of C7 in the affected siblings and half of the normal values in their parents were found in both families. The variant responsible for the deficiency (C7Q*0) follows a codominant autosomic inheritance pattern. Establishing allotypes of C6 and C7 by isoelectrofocusing followed by electrophoretic immunoblotting allowed haplotype assignments. In both families the haplotype form responsible for the deficiency seemed to be related to the C6B allotype. PMID- 2225796 TI - A novel immunoassay for the quantitation of human C4 gene products. AB - Utilizing mouse monoclonal antibodies which recognize Rodgers 1 and Chido 1 epitopes carried on the C4A and C4B molecules, and heat-aggregated IgG to activate C1, an immunoassay was developed for the quantitation of total C4 as well as C4A and C4B. Interassay variation was 12.4, 11.5 and 10.8%, respectively. The immunoassay was compared to the quantitation of total C4 by radial immunodiffusion by testing 103 random white controls and gave a Pearson's product moment correlation coefficient of 0.81. Three genetic total-C4-deficient individuals were nonreactive in all three assays. This activated assay is specific, reproducible, and superior to existing methods for the quantitation of C4A and C4B and detection of the heterozygous C4 null state. PMID- 2225797 TI - On defining delusions. AB - The DSM-III-R definition of delusions bears inconsistencies and does not account for the way delusions are detected clinically. It can be traced back to Karl Jaspers who was the first to mention the three criteria of delusions, which are to be found in the textbooks ever since: (1) certainty, (2) incorrigibility, and (3) impossibility or falsity of content. Psychiatrists always felt uncomfortable with the third criterion, and Kurt Schneider pursued the most thorough attempt to dispose of this criterion by his definition of delusional perception. It can be shown that while his definition is wrong, the phenomena he had in mind do, in fact, have some distinctive features. Proceeding from the first two criteria of Jaspers, a new definition is proposed that emphasizes the way certain contents are stated and disregards the issue of right or wrong. Advantages of this definition are discussed and a distinction between delusions (about external reality) and certain actual experiences (happening in the patient's mind) is proposed. PMID- 2225798 TI - Care strategies for schizophrenic patients in a transcultural comparison. AB - This study was conducted in order to test the hypothesis derived from the International Pilot Study of Schizophrenia (IPSS) that the existence of extended families in developing countries contributes to the more favorable course and outcome of schizophrenia in these countries in comparison with industrial countries. For this purpose, we compared data from the 5- and 10-year follow-up obtained within the IPSS at Cali, Colombia with data from two 5- to 8-year follow up studies of former schizophrenic inpatients of the Max Planck Institute of Psychiatry (MPIP) in Munich, FRG. Although, in Cali, schizophrenics are hospitalized and treated with drugs only during acute episodes of the psychosis and no facilities exist for long-term treatment, the psychopathological outcome was, on the whole, not worse than in Munich. Furthermore, the duration of hospitalization during the follow-up period was much lower at Cali and a significantly lower number of Colombian than of German patients was not separated from their families. However, contrary to the hypothesis, family size did not predict course and outcome at both centers. PMID- 2225799 TI - Delimitation of generalized anxiety disorder: clinical comparisons with panic and major depressive disorders. AB - We compared 40 outpatients with "pure" generalized anxiety disorder (GAD) with 152 panic disordered patients with varying degrees of phobic avoidance, and 241 primary major depressives with single and recurrent episodic patterns. Despite sociodemographic and symptomatologic overlaps with these comparison groups, GAD emerged as a relatively distinct disorder, characterized by chronic low-grade symptomatology with observed anxiety at interview, as well as nausea, headache, tension, and insomnia. These anxious "traits," which appear to be part of the habitual self of the patient, are subject to fluctuation over time, and may form the temperamental substrate or precursor of panic and other anxiety and depressive disorders. PMID- 2225800 TI - A clinical and demographic profile of a sample of adults with attention deficit hyperactivity disorder, residual state. AB - It is becoming increasingly recognized that one third to one half of children diagnosed as having attention deficit/hyperactivity disorder (ADHD) continue to exhibit symptoms of the disorder into adulthood. The nature of the clinical picture is not well understood by a substantial number of clinicians. The purpose of this study is to report on the demographic and clinical profile of 56 adults, age 19 to 65 years (48 men, eight women) who present with adult ADHD and meet DSM III-R criteria for the disorder. Patients underwent a diagnostic work-up consisting of medical and psychiatric evaluation, a structured interview Schedule for Affective Disorders and Schizophrenia-Lifetime Version [SADS-L]), the Symptoms Checklist Revised (SCL-9OR), Conners Attention Deficit Disorder With Hyperactivity (ADDH) scale, structured interview of ADDH, the Global Assessment of Functioning Scale (GAF), and, when available, information from parents was obtained. Ninety-one percent of our sample met the Utah Criteria for adult ADHD. The majority of the sample had additional DSM-III-R diagnoses and only seven had ADHD diagnosis alone. Fifty-three percent of the sample met the criteria for generalized anxiety disorder, 34% alcohol abuse or dependence, 30% drug abuse, 25% dysthymic disorder, and 25% cyclothymic disorder. These findings were similar to those reported in the literature. PMID- 2225801 TI - Psychological mindedness as a predictor of psychotherapy outcome: a preliminary report. AB - This study investigated the properties of a new measure of psychological mindness (PM). A 45-item self-report questionnaire was administered to consecutive admissions to a large outpatient clinic that provides primarily psychodynamically oriented individual psychotherapy. The PM scores of a sample of 44 of these patients who attended a median of 15 sessions were correlated with several outcome measures obtained from retrospective chart reviews. These measures consisted of the number of sessions attended, discharge ratings, and change scores on a Global Assessment Scale (GAS) and on a symptom checklist. Coefficient alpha for the Psychological Mindedness (PM) Scale indicated high reliability. Total PM score correlated significantly with three of the outcome measures. Twenty of the 45-items were good predictors of one or more outcome measures. PMID- 2225802 TI - DSM-III personality disorders in obsessive-compulsive disorder: changes with treatment. AB - Twenty-seven patients meeting DSM-III diagnostic criteria for obsessive compulsive disorder (OCD) completed the Personality Diagnostic Questionnaire (PDQ; a self-rating scale designed to assess the axis II personality disorders [PDs] from the DSM-III) before and after 12 weeks of treatment with clomipramine. Treatment was accompanied with reduction on several personality variables, including the number of personality diagnoses assigned, the distribution of traits in the sample, and the number of items endorsed in each personality category. The data also showed that improvement in personality functioning was significantly greater in responders compared with nonresponders or partial responders. Further investigation of the relationship between personality and treatment outcome did not provide strong support for the notion that personality factors may have prognostic significance in the treatment of OCD. These findings suggest similarities and differences with panic/agoraphobia which are briefly discussed. PMID- 2225803 TI - Andre G. Ombredane and the psychiatry of multiple sclerosis: a conceptual and statistical history. AB - By means of conceptual history and statistical analysis of historical data, this report shows that studies into the psychiatry of multiple sclerosis (MS) underwent a qualitative improvement between the Great War and the publication of A.G. Ombredane's great work. Analysis of his database, collected 60 years ago, shows that some of his conclusions (later to be influential) were unwarranted, but that, on the other hand, it enshrined hidden information showing a relative independence between euphoria (and other affective changes) and chronicity and illness duration. An earlier knowledge of this point might have had a corrective effect on later claims about the neuropsychiatry of MS. PMID- 2225804 TI - Capgras' delusion: an example of coalescent psychodynamic and organic factors. AB - The case of a 33-year-old woman with a right hemisphere lesion after subarachnoid bleed is reported. She developed the false belief that her husband, her mother, her children, and herself had been replaced by doubles after the birth of her fourth daughter. The multifactorial etiology of the Capgras delusion is discussed with a brief review of the literature. PMID- 2225806 TI - The symptom pattern variations of unipolar depression during life span: a cross sectional study. AB - The psychopathological syndromes are analyzed for 436 patients suffering from a unipolar affective psychosis, depressed type, without any further psychiatric or somatic diagnosis, separately for the second to eighth decade of life. The intensity of the depressive syndrome, as well as the apathy syndrome according to the Manual for the Assessment and Documentation of Psychopathology (AMDP) system, does not decrease. The autonomic syndrome increases for the group in the involutional age, and the psycho-organic syndrome for the group in the old age. The analysis of special symptom patterns, as for the agitated behavior or symptoms of the psycho-organic syndrome, is presented. PMID- 2225805 TI - A self-report measure of violence risk, II. AB - A brief self-report scale designed to measure the risk of violence was developed. Scale scores were found to be significantly related to a history of violence, or violence as a reason for admission, in psychiatric inpatients. Internal reliability was found to be high. A group of psychiatric inpatients could be significantly discriminated from a normal group of individuals, both on total scale score as well as on each individual item. Sensitivity and specificity were also determined. The value of the scale is in its brevity, in its focus on overt behavior as well as feelings, and in the fact that it defines a profile of characteristics that have been found to be associated with violent behavior. It thus represents a useful tool for future research on human aggression. PMID- 2225807 TI - Toward a new nosology of obsessive compulsive disorder. AB - Obsessive compulsive disorder (OCD) is receiving increasing attention in the clinical research literature. This review briefly summarizes data concerning diagnosis, phenomenology, and epidemiology of OCD and examines other disorders that closely resemble OCD. In addition, the nosological and treatment implications of these data are discussed. We find that OCD is characterized by a focal anxiety point(s) reflected in obsessions and by behavioral or cognitive compulsions. The appearance of these characteristics in other disorders suggests some relation between them and, consequently, the treatment of these disorders may be enhanced by conceptualizing them as OCD "variants". PMID- 2225808 TI - Heart-lung transplantation: initial experience in New England. AB - Between May 1988 and June 1989, five combined heart-lung transplants were performed. There were two males, age 16 and 19 years, and three females age 33, 34, and 19 years. Three patients had primary pulmonary hypertension, one had cystic fibrosis, and the fifth had doxorubicin-induced cardiomyopathy with associated pulmonary hypertension. All patients were severely restricted in functional capacity and were oxygen-dependent. Four grafts were distantly procured (ischemic times 1:15, 2:35, 2:45, 3:45); one was procured on-site (ischemic time 0:58). Four of five grafts functioned well (PO2 on FIO2 30% postoperatively: 102, 120, 180, and 129 torr). One graft (distantly procured with an ischemic time of 1:15) showed total failure of oxygenation secondary to fluid overload during donor surgery; the recipient could not be weaned from cardiopulmonary bypass. All patients were extubated 24 to 30 hours postoperatively. Rejection episodes have been infrequent and all have been successfully treated with pulse steroids. Four of the five patients are alive and well with normal cardiopulmonary function and normal functional capacity 15, 12, 8, and 6 months after surgery. Heart-lung transplantation is an effective therapy for properly selected patients with end-stage cardiopulmonary disease resulting from a variety of primary disorders. PMID- 2225809 TI - Babesiosis in a Connecticut resident. AB - Fewer than 200 confirmed cases of babesiosis have been reported in the last decade. Most cases in the United States have occurred on Cape Cod, Nantucket Island, and Long Island. Babesia microti, a malaria-like protozoan that parasitizes erythrocytes, is responsible for this illness in the United States. Infection is often subclinical but may be fulminant, especially in infants, the elderly, and in asplenic patients. Symptoms are nonspecific, usually consisting of fever and myalgias. Common laboratory abnormalities include evidence of hemolysis and thrombocytopenia. We report a case of babesiosis in an elderly male manifested by high fevers, confusion, hemolytic anemia, and thrombocytopenia. PMID- 2225810 TI - Fluconazole. PMID- 2225811 TI - Surgery for epilepsy. National Institutes of Health. PMID- 2225812 TI - Dam the blood. PMID- 2225813 TI - Confidentiality and the courts. PMID- 2225815 TI - Role of MRI in meningiomas: with and without gadopentetate. AB - Seventeen patients (15 newly diagnosed and two recurrent) with meningiomas were studied by magnetic resonance imaging (MRI) operating with 0.3, 0.5, and 1.5 Tesla magnets. In four patients gadopentetate dimeglumine was administered, following a noncontrast scan. In all the patients the tumors were isointense with the cortex at short relaxation and echo times (TR and TE) and became hyperintense with the increase in TR and TE on 0.3, 0.5, and 1.5 Tesla magnet systems. MRI correlated well with angiography in the detection of sagittal sinus thrombosis, and delineated tumor from edema as in computed tomography. Elimination of bony artifacts made detection of posterior fossa tumors easier with MR scanning. Gadopentetate dimeglumine shortened the scan time, displaying small tumors as well as sagittal sinus involvement to advantage. In these respects, we believe MRI is more effective than computed tomography in the diagnosis and management of meningiomas. PMID- 2225816 TI - Colocolic intussusception in a three-year-old child caused by a colonic polyp. AB - Colocolic intussusception is an uncommon cause of pediatric intestinal obstruction in North America; 95% of cases are ileocolic in location, with an equal percentage in which no pathologic lead point is evident on barium enema or laparotomy. In the last 20 years less than 3% of approximately 32,500 reported cases of intussusception originated in the colon. In a significant number of these cases juvenile polyps were identified as leading points. The majority of juvenile polyps occur in the rectosigmoid colon within the reach of a standard pediatric sigmoidoscope. These tumors most often cause painless hematochezia. Occasionally, juvenile polyps may grow large and serve as lead points for colocolic intussusception when located in the proximal colon. Pediatric patients presenting with documented colocolic intussusception should suggest the possibility of a colonic polyp or other mass lesion. Careful physical examination and barium studies should provide important diagnostic clues. Treatment is aimed at removing the lead point in patients presenting with intestinal obstruction. Colonoscopic polypectomy performed by an experienced endoscopist may serve as an alternative to surgical removal of the polyp. We report a case in a three-old child of colocolic intussusception caused by a colonic polyp, and review some of the salient features of this clinical entity. PMID- 2225814 TI - Connecticut's new abortion statute. PMID- 2225817 TI - Creosote: a short history of its medicinal uses. PMID- 2225818 TI - Variations in coding practices among Connecticut urologists for the Medicare population. AB - As health care costs continue to rise, alternatives to the traditional fee for service system of physician reimbursement are being explored. Recently a resource based relative-value system was enacted by Congress to correct some of the perceived inequities of Medicare reimbursement. Since reimbursement for evaluation and management services, also known as cognitive services, are based on Current Procedural Terminology (CPT-4) codes, we reviewed Medicare claims data for fiscal year 1986-87 to identify the coding habits of Connecticut urologists. We found that Connecticut urologist file 99% of their claims for cognitive services in one of six categories. Furthermore, we found that within these broad categories an average of 82% of the claims were filed under one primary practice specific code. The particular code selected, however, varied markedly between practices. Our data suggest that Connecticut urologists have adopted different standards for using CPT-4 codes and have adjusted for these differences through their fee schedules. These findings highlight the need for increased precision in CPT code definitions for cognitive services before they can be adapted to a reimbursement system based upon relative-value scales. PMID- 2225819 TI - Consensus conference. The treatment of sleep disorders of older people. National Institutes of Health. PMID- 2225820 TI - National Practitioner Data Bank begins. American Medical News. PMID- 2225821 TI - The National Practitioner Data Bank and credentialing. PMID- 2225822 TI - Insurance companies intrude in doctor-patient relationships. PMID- 2225823 TI - Love and service. PMID- 2225824 TI - Exasperating the ways of death. PMID- 2225825 TI - The abortion czar. PMID- 2225827 TI - Terminal renal failure: therapeutic problems, possibilities, and potentials. International symposium of renal failure: past, present, and future. Malmo/Lund, Sweden, June 9-11, 1989. Proceedings. PMID- 2225826 TI - Historical overview of renal failure therapy--a homage to Nils Alwall. PMID- 2225828 TI - Protein metabolism and nutrition in hemodialysis patients. PMID- 2225829 TI - Membranes for blood purification: state of the art and new developments. PMID- 2225830 TI - Possibilities of selective and unselective adsorbent development in blood purification. PMID- 2225832 TI - The clinical practitioner and expert systems. PMID- 2225831 TI - A bioartificial pancreas to prevent diabetic microangiopathy? PMID- 2225833 TI - Treatment of terminal renal failure in the western European countries. PMID- 2225834 TI - Present status of ESRD treatment in Japan. Report from the Patient Registries of Dialysis and Kidney Transplantation. PMID- 2225835 TI - Quantity and quality of ESRD treatment in the United States of America. PMID- 2225836 TI - Treatment of ESRD in eastern Europe. PMID- 2225837 TI - Dialysis hypotension. PMID- 2225838 TI - Pathophysiologic aspects of plasma volume preservation during dialysis and ultrafiltration. PMID- 2225839 TI - Cardiovascular problems in end-stage renal failure: haemofiltration. PMID- 2225840 TI - Towards new therapeutic strategies in renal disease. PMID- 2225841 TI - The anemia of chronic renal failure: pathophysiology and effects of recombinant erythropoietin. PMID- 2225842 TI - Renal osteodystrophy: past and future. PMID- 2225843 TI - Dialysis amyloidosis: current disease concepts and new perspectives for its treatment. PMID- 2225844 TI - Hypertension and glomerular sclerosis: where, when and how? PMID- 2225846 TI - Angiotensin, ACE inhibition, and the renal circulation: pathogenesis of nonmodulation in essential hypertension. PMID- 2225847 TI - Radionuclides in nephro-urology. 7th international symposium. Williamsburg, Va., May 7-10, 1989. Proceedings. PMID- 2225845 TI - Preventing or postponing renal disease in insulin-dependent diabetes by glycemic and nonglycemic intervention. PMID- 2225848 TI - The uses and interpretation of modified diuresis renography. PMID- 2225849 TI - Prospective evaluation of radionuclide monitoring in renal transplantation. PMID- 2225850 TI - The intrarenal kinetics of hippuran in acute rejection of renal allograft. PMID- 2225851 TI - The effects of increased dialysate sodium concentration on skeletal muscle and subcutaneous blood flow during hemodialysis. Dialysate sodium and regional blood flow. PMID- 2225852 TI - Assessment of renal volume in vivo using SPECT. PMID- 2225853 TI - Long-term follow-up of separate glomerular filtration rate in partially obstructed kidneys. PMID- 2225854 TI - Comparison of conventional furosemide diuresis renography with direct intrapelvic infusion renography. PMID- 2225855 TI - Serial furosemide renography in asymptomatic hydronephrosis diagnosed by ultrasound in utero and neonatally. PMID- 2225856 TI - Paradoxical increased glucoheptonate uptake in experimental renovascular hypertension. PMID- 2225857 TI - Captopril-stimulated renography versus renal vein renins in two-kidney, two-clip hypertension. PMID- 2225858 TI - Detection of renal artery stenosis by means of captopril renography with 99mTc DTPA. PMID- 2225859 TI - Captopril renography and duplex sonography: comparison of two noninvasive methods for the diagnosis and follow-up in renovascular hypertension. PMID- 2225860 TI - Results of quantification of frusemide response in 123I-hippuran renal studies of unilateral renal artery stenosis. PMID- 2225861 TI - Usefulness of renal sequential scintigraphy for the evaluation of antihypertensive drugs. PMID- 2225862 TI - Captopril radionuclide test in renovascular hypertension. A European multicenter study. PMID- 2225863 TI - Captopril scintirenography: a protocol to assess efficacy and methodology. A collaborative study. PMID- 2225864 TI - Lasix captopril renography in the diagnosis of renovascular hypertension. PMID- 2225865 TI - Renal imaging of thallium-201 during cardiac evaluation. PMID- 2225866 TI - The permeability of the human bladder to water assessed using tritiated water. PMID- 2225867 TI - Prolonged constant dual-isotope infusion for determination of renal function after water loading in hypertensive diabetic men. PMID- 2225868 TI - Simultaneous measurement of glomerular filtration rate and effective renal plasma flow reveals increased glomerular capillary pressure among teenage diabetic subjects. PMID- 2225869 TI - Clinical evaluation of the filtration fraction: multivariate statistical analysis. PMID- 2225870 TI - Renal tubular reabsorption of calcium in primary hyperparathyroidism. PMID- 2225871 TI - The impact of different urinary flow rates on renoscintigraphy. PMID- 2225872 TI - Renal function, urinary flow rates and diuresis renography. PMID- 2225873 TI - Validation of a new method for quantifying renal function. PMID- 2225874 TI - The radionuclide renal scan: past, present and future. PMID- 2225875 TI - Abnormal renal mobility: radionuclide features and clinical relevance. PMID- 2225876 TI - Acute effect of urapidil on peripheral serotonin metabolism. AB - In a cross-over study, the effect of 25 mg urapidil infusion (U, Ebrantil 25, Byk Gulden, FRG) on serotonin (5HT) metabolism and platelet aggregation (PA) was compared with the effect of placebo (P) in 7 patients with essential hypertension. No changes in 5HT and 5-hydroxyindolacetic acid (5HIAA) plasma levels and platelet 5HT content were observed. PA induced ex vivo by ADP decreased significantly. 5HIAA urinary excretion and fractional excretion (FE) increased, while 5HT renal metabolism changed only moderately. No changes in adrenaline and noradrenaline excretion were observed. In in vitro studies, U in therapeutic levels decreased ADP-induced PA and completely inhibited 5HT-induced PA (platelets of healthy volunteers). It is suggested that U has a direct antiaggregatory effect through 5HT2 receptors of platelets. PMID- 2225877 TI - New methods of diagnosing receptor metabolism disturbances of low density lipoproteins. AB - The authors present new approaches to assessment of various aspects of receptor metabolism for low density lipoproteins in patients with atherosclerosis: the ability of lipoproteins to interact with cell receptors in culture in the presence of nonfractionated serum; analysis of the genetically determined number of LDL receptors on culture cells, and the in vivo lipoprotein uptake in the liver. The ability of apo B-containing lipoproteins in patients with atherosclerosis to interact effectively with cell receptors was confirmed, the activity of LDL receptors on cells in cultures from patients with hypercholesterolaemia was analysed, and a decrease in 99mTc-labelled LDL uptake in the liver of patients with the heterozygous form of familial hypercholesterolaemia was demonstrated. The above approaches could be useful in the choice of individual treatment of clinically manifest atherosclerosis and evaluation of therapeutic efficacy. PMID- 2225878 TI - Significant X-ray patterns in cardiomyopathy--an approach improving noninvasive diagnosis. AB - To identify their characteristic patterns, the X-ray dorso-ventral chest images of 118 patients with cardiomyopathy (63--dilated cardiomyopathy, 25--hypertrophic obstructive cardiomyopathy, 30--hypertrophic nonobstructive cardiomyopathy) were analyzed and compared with those of 22 patients without cardiac abnormalities. All 140 patients underwent comprehensive invasive cardiac examinations. In dilated and hypertrophic nonobstructive cardiomyopathy transvasal endomyocardial biopsy was performed. Irrespective of the type and the aetiology of cardiomyopathy, 4 characteristic patterns of X-ray findings could be identified: a class of left heart abnormality (class L) and 3 types of bilateral cardiac abnormalities with various stages of left heart failure (class L + R). An association between the image patterns and haemodynamic parameters (left ventricular end-diastolic pressure, wall mass index, pulmonary mean pressure) was demonstrated which was most obvious in dilated and less evident in hypertrophic obstructive cardiomyopathy. Mitral insufficiency in all types and classes frequently corresponded with the X-ray findings of left atrial enlargement. The X ray classification method proved to be an efficient approach and superior to the heart-to-lung ratio. PMID- 2225879 TI - Cardioprotective conditioning with glucose and insulin prior to cardiac surgery involving ischaemic cold arrest. AB - The study describes cardioprotective conditioning by means of high doses of glucose together with insulin and potassium. Eighteen hours before cardiac surgery, nine patients received continuous infusion of 1000 ml of 40% glucose solution along with 112 U of insulin and 60 mmol of potassium. Before and after ischaemic cold arrest, the myocardial a--v differences of lactate, pyruvate, glucose, Na, K, Cl, Ca, P, free fatty acids and triglycerides were analysed in all patients. Blood collections were performed in parallel with ultramicroscopy of biopsy specimens from the right atrium. The results were compared with those obtained in a control group of 22 patients without cardioprotective conditioning with glucose, insulin and potassium. Neither the analysis of the myocardial a--v differences of metabolites, nor the finding on the mitochondria and myofibrils documented statistically significant differences between the control and conditioned groups. Following termination of ischaemic cold arrest, patients in the conditioned group exhibited more glycogen grains in myocardial cells than those in the control group. While 34% of patients in the control group were defibrillated after revascularization, it was not necessary in any of the conditioned patients. PMID- 2225880 TI - Different levels of cardiovascular risk factors in type-2 diabetic patients with lower limb proximal and distal vessel macroangiopathy. AB - The levels of some cardiovascular risk factors (lipids, apolipoproteins and fibrinogen) were measured in groups of Type-2 diabetic patients with lower limb proximal (ileofemoral) and distal (trifurcational) artery macroangiopathy, diagnosed by Doppler ultrasound, and in a group of diabetics without macroangiopathy. The highest mean levels of total and LDL-cholesterol, apolipoprotein B and triacylglycerols were observed in patients with proximal vessel involvement. Significant correlations were found between the thigh/arm index and total cholesterol, LDL-cholesterol, apolipoprotein B and stroke prevalence. On the other hand, a significant correlation was found between ankle/thigh index and fibrinogen. The results of the study suggest that different pathogenetic mechanisms may play a role in the development of ileofemoral and trifurcational vessel disease. PMID- 2225881 TI - The amputation level: noninvasive methods and clinical criteria. AB - Before undergoing amputation of a lower limb, one hundred and forty-six patients suffering from arteriosclerosis were studied with the purpose of finding prognostic indicators of success at the most distal level. The best results were obtained when skin perfusion pressure was above 60 mmHg in diabetics and above 40 mmHg in non-diabetics. Lower limb systolic blood pressure and skin thermometry also proved to be useful. The method proposed might be helpful to the surgeon in choosing the best treatment for the patient. It is a nonivasive procedure which can be easily performed and does not require sophisticated or expensive equipment. PMID- 2225882 TI - The number and some other characteristics of isolated human ventricular cardiomyocytes under pathological conditions. AB - Using a modified method for alkalic dissociation, isolated ventricular cardiomyocytes were obtained from eight patients who had died of different diseases. The absolute number of cardiomyocytes, counted in the Fuchs-Rosenthal chamber, ranged between 1.10 x 10(9) and 3.25 x 10(9) in the left ventricle, and between 0.58 x 10(9) and 1.42 x 10(9) in the right ventricle depending on myocardial mass. Mean volume of cells ranged between 75 x 10(3) and 344 x 10(3) microns3, and the content of polynuclear, predominantly binucleated, cardiomyocytes amounted to 14 to 49%. An increase in ventricular myocardium mass was associated with an increase in cardiomyocyte volume. A negative correlation was demonstrated between the absolute number of cardiomyocytes on the one hand, and their mean volume and proportion of polynuclear cells on the other. PMID- 2225883 TI - Romano-Ward syndrome: case report, family study and signal averaged electrocardiogram. AB - A family with the Romano-Ward syndrome is described. A 28-year-old woman had episodes of syncope due to self-terminating ventricular tachycardia torsades de pointes. During lidocaine treatment she developed a sustained ventricular tachycardia and cardiopulmonary resuscitation was necessary. Propranolol reduced ventricular ectopic activity, but the QTc interval remained prolonged. A "threshold" in QT duration for the generation of complex ventricular arrhythmias was observed in the patient. There were no late ventricular potentials noted in the signal averaged ECG in the patient and in members of her family. PMID- 2225884 TI - Use of myocardial skinned fibres for the study of mitochondrial oxidative phosphorylation during ischaemia. AB - The authors studied mitochondrial oxidative phosphorylation in the skinned myocardial fibres of the rat and the rabbit during ischaemia. Saponin action on tissue was used to remove the sarcolemma while leaving the interior of intracellular structures intact. Mitochondrial oxidative phosphorylation was measured by polarography using Clark's oxygen electrode in the presence of NAD- and FAD-substrates. The skinned fibre method is rapid and very simple. The fact no more than 5-10 mg of tissue is needed to perform it makes it suitable for the study of metabolic processes in experimental and clinical cardiology, under physiologic conditions as well as during ischaemia. PMID- 2225885 TI - Depression and recovery of right ventricular function after cardiopulmonary bypass. AB - Transient left ventricular dysfunction is commonly described in association with cardiopulmonary bypass (CPB). We evaluated changes in right ventricular (RV) function after elective cardiac surgery in 24 patients with normal preoperative cardiac function. In all, irrespective of distribution of coronary artery disease or use of pharmacologic support, a transient depression of RV systolic function with respect to both preinduction and initial postoperative (Postop) values occurred 262 +/- 116 min post-CPB as represented by a decrease in RV stroke volume index (25.0 +/- 1.7 vs. 33.4 +/- 1.9 ml/m2 Postop) and RV ejection fraction (31.0 +/- 2.2 vs. 45.6 +/- 2.5% Postop), and an increase in RV end systolic and end-diastolic volume indices. This depression responded readily to pharmacologic therapy within 2 h, resolved within 24 h, and had no adverse consequences in these otherwise healthy patients. Further studies are needed to identify the cause of this phenomenon and its importance in patients with preexisting cardiac dysfunction. PMID- 2225886 TI - Community-acquired pneumonia: evidence of functional inactivation of alpha 1 proteinase inhibitor. AB - Quantitative and qualitative elastase inhibitory capacity (EIC) alpha 1 proteinase inhibitor (alpha 1 PI) was measured in pulmonary arterial and systemic arterial blood of patients with community-acquired pneumonia (CAP). Eleven patients with uncomplicated CAP were compared with 16 patients with fulminating pneumonia requiring intensive care management. An appropriate increase in quantitative alpha 1 PI was demonstrated in all patients. A significant functional inactivation of alpha 1 PI was demonstrated in the ICU-treated patients that was not apparent in the uncomplicated CAP patients (p less than .01). This low EIC returned to normal 4 wk after hospital discharge in all survivors. A significant (p less than .02) difference in EIC between the pulmonary arterial and systemic arterial blood was found in the nonsurvivors on admission, which suggests that alpha 1 PI is inactivated in the lungs of patients with fulminating CAP. The present data demonstrate that alpha 1 PI is functionally inactivated in patients with fulminating CAP. This low serum functional alpha 1 PI may result in proteolytic lung damage and an unfavorable outcome. PMID- 2225887 TI - Hypophosphatemia--incidence, etiology, and prevention in the trauma patient. AB - Hypophosphatemia is associated with a number of undesirable physiologic consequences and has been reported to occur frequently in trauma patients. We studied patients in the immediate posttraumatic period to document a) the decrease in serum P, b) renal P excretion, and c) the response to prophylactic PO4 administration. In both group 1 (n = 12) and group 2 (n = 10) patients, we measured serum P, creatinine, ionized Ca, urinary P excretion, and creatinine clearance daily for the first 3 to 4 days postinjury. Patients in group 2 also received 0.5 mmol/kg.day of PO4 for the first 48 h after admission. Group 1 patients exhibited a significant (p less than .05) decrease in serum P over the first 24 h (1.00 +/- 0.30 to 0.75 +/- 0.23 mmol/L). In contrast, group 2 patients did not demonstrate a decrease in serum P. Urinary P excretion in group 1 accounts for the observed decrease in serum P. The results of our study show that the immediate posttraumatic period is associated with a decrease in serum P and massive urinary P excretion. We also showed that prophylactic administration of 0.5 mmol PO4/kg.day prevents serum P decrease. PMID- 2225888 TI - Hypocalcemia and hypercalcitoninemia in critically ill children. AB - To study Ca metabolism in critically ill children, we measured ionized Ca (Ca2+), parathyroid hormone (PTH), calcitonin, 25 hydroxycholecalciferol (25[OH] D3), 1 25 dihydroxycholecalciferol (1-25[OH]2D3, and gastrin levels in critically ill children and in healthy controls. Patients were considered hypocalcemic if Ca2+ was less than 1.1 mmol/L. Six (14%) of 45 patients were hypocalcemic. Five hypocalcemic patients were studied and were found to have higher calcitonin levels than normocalcemic patients and healthy controls and higher PTH levels than healthy controls. 25(OH)D3 and 1-25(OH)2D3 were not significantly different in the three groups of patients. Gastrin levels were low in critically ill patients, whether or not they were hypocalcemic. We conclude that hypocalcemia occurs frequently in critically ill children. It is associated with raised levels of calcitonin and PTH. The mechanism for the increase in calcitonin is unknown. PMID- 2225889 TI - Jugular bulb catheterization: experience with 123 patients. AB - Jugular bulb catheterization (JBC) provides cerebral venous access for titration of brain-specific therapy. Little has been written about the catheterization procedure. We prospectively studied the time, number of punctures, success rate, and complications during JBC for a 24-month period in our ICUs. One hundred twenty-three patients (mean age 6.7 yr, range 12 hours to 21 yr) underwent JBC. Procedure time was 15.6 +/- 5.0 (SD) min. Median number of skin punctures was two. All but four were successful on first attempt. Three of the remaining were catheterized on second attempt. Inadvertent carotid puncture occurred in 3%. No other significant complications were noted. Radiography confirmed proper position in 97%. Duration of indwelling venous catheters was 2.5 +/- 1.6 days. All catheters functioned well until removal. We conclude that our technique of JBC is safe and highly successful. It compares favorably with previous, smaller series and with standard anterograde internal jugular catheterization in both children and adults. PMID- 2225890 TI - Assessment of creatinine clearance in intensive care patients. AB - Assessment of creatinine clearance (CC) in ICU patients was compared using three methods. The reference method (CC 24 h) used measurements of serum creatinine and urinary creatinine after collection of urine over a 24-h period. The other two methods were predictive methods: the Kampmann nomogram and the formula developed by Gault and Cockcroft. The two predictive methods correlated well with one another. Correlation between the predictive and the reference methods was poor or absent. A discriminant analysis revealed that measurement of urinary creatinine was a major factor in CC estimation. In conclusion, the reference method of CC assessment is preferred to obtain a reliable estimation of glomerular filtration rate in ICU patients. PMID- 2225891 TI - Timing of intensive care unit admission in relation to ICU outcome. AB - This study assessed the relationship between admission time (from hospital admission to ICU admission) and mortality predicted by the Mortality Prediction Model (MPM), actual mortality, and resource use. All admissions, except elective surgery patients, to the general medical/surgical ICU of a tertiary care hospital during a 24-month period were studied (n = 1,889). Patients admitted to the ICU within 1 day of hospital admission had lower predicted and actual mortality, and used fewer resources than patients admitted later. Predicted mortality was higher than actual mortality for patients admitted to the ICU early and was lower than actual mortality for later ICU admissions. Transfers had higher predicted and actual mortality, and used more resources than nontransfer patients. Time from hospital admission to ICU admission can be a potentially useful variable in models of ICU outcome. PMID- 2225892 TI - Tracheostomy in children with Guillain Barre syndrome. AB - During the 10-yr period beginning January 1979, 59 infants and children with Guillain Barre syndrome (GBS) were admitted to our hospital. Tracheostomies were performed in 15 patients and their records were reviewed. Fourteen patients were recalled for assessment of pulmonary function and respiratory muscle strength (RMS). The median duration of assisted ventilation (including endotracheal [ET] intubation) was 21 days and the median duration of tracheostomy was 39 days. Only two patients were discharged with the tracheostomy in situ. All patients were successfully decannulated at the first attempt. No tracheostomy-related complications or symptoms were reported apart from croup in two patients. On review, lung volumes and maximal inspiratory and expiratory flows were normal. There was no evidence of tracheal stenosis or significant tracheomalacia. RMS tests were normal. In this hospital, tracheostomy is a safe, well-tolerated procedure in the management of infants and children with GBS who need long-term ventilation. There were no deaths and all patients returned to their normal school or were gainfully employed after their illness, although 12 patients had mild persistent weakness of at least foot dorsiflexion. PMID- 2225893 TI - Prevention of nosocomial lung infection in ventilated patients: use of an antimicrobial pharyngeal nonabsorbable paste. AB - A comparative, prospective study was made of the incidence of infection in the lower airway (purulent tracheobronchitis and pneumonia) in long-term patients who were mechanically ventilated due to respiratory failure of noninfectious origin. Twenty-eight patients were randomly allocated into a study group (A, n = 13) in which a nonabsorbable paste containing 2% tobramycin, 2% amphotericin B, and 2% polymyxin E was administered locally to decontaminate the oropharynx, and a control group (B, n = 15) in which a paste without antibiotics was also applied to the oropharynx. We studied the effectiveness of the prophylactic technique in decontaminating the oropharynx and trachea of organisms potentially pathogenic for the respiratory system. Decontamination was successful in ten of 13 patients in group A vs. one of 15 patients in group B (p less than .001). The results demonstrated a lower rate of infection in the lower respiratory tract in the study group (three patients with tracheobronchitis and no pneumonias) than in the control group (three patients with tracheobronchitis and 11 with pneumonia), the difference between both being highly significant (p less than .001). Two (15%) patients in group B developed sepsis of pulmonary origin. None of the patients on prophylactic treatment developed this complication. Although the overall mortality was similar in both groups (group A, 30% vs. group B, 33%), we believe that infection contributed to a great extent to the death of two of five patients in group B. We conclude that nosocomial pneumonia, which is a frequent complication in critically ill patients on mechanical ventilation, could be prevented by local application of nonabsorbable antibiotics to the oropharynx. PMID- 2225894 TI - Iatrogenic illness in pediatric critical care. AB - Iatrogenic illness may be an important determinant of the need for pediatric intensive care. We prospectively evaluated consecutive admissions to a pediatric ICU (PICU) over two time periods totaling 6 months. Twenty-five (4.6%) admissions were necessitated by iatrogenic illnesses. Drug-induced conditions accounted for eight (32%) of the iatrogenic patients, and complications of medical-surgical acts accounted for 17 (68%). Diagnoses included six respiratory failures due to seizure medications, six chronic upper airway complications of neonatal intensive care, four posttonsillectomy and postadenoidectomy complications, two chronic postcardiac surgery complications, two cardiac catheterization complications, and five miscellaneous conditions. One (3.7%) patient with iatrogenic illness died. As a group, patients with iatrogenic illness were at a risk of dying similar to other patients. We conclude that iatrogenic illness is a significant cause of PICU admission. PMID- 2225895 TI - Effects of intravenous immunoglobulin on hemorrhage-induced alterations in plasma cell repertoires. AB - Hemorrhage produces decreases in serum immunoglobulin (Ig) levels and alterations in the number and frequency of B cells producing antibodies against bacterial antigens. These abnormalities in immune response may contribute to the increased susceptibility to infection after injury and hemorrhage. To examine the relationship between serum Ig levels and bacterial antigen-specific plasma cell numbers and frequencies after blood loss, we treated hemorrhaged mice with intravenous Ig (IVIG). Hemorrhaged mice given IVIG had increased total numbers of splenic plasma cells compared with normal or hemorrhaged, untreated mice. Immunization with the bacterial polysaccharide antigen levan immediately after hemorrhage resulted in approximately 60% fewer levan-specific splenic plasma cells than those seen in normal unhemorrhaged mice. Treatment of hemorrhaged mice with IVIG did not correct the decrease in levan-specific plasma cells. These results demonstrate that hemorrhage-induced alterations in the numbers and frequencies of bacterial antigen-specific B cells are not related to changes in serum Ig levels and cannot be corrected through administration of IVIG. PMID- 2225896 TI - High-frequency oscillation during simulated altitude exposure. AB - Ventilatory requirements using high-frequency oscillation (HFO) during simulated altitude exposure were investigated in control dogs and animals with oleic acid induced lung injury. FIO2 values of 0.21 and 1.0 were supplied by bias flow to the normal and injured dogs, respectively. After a control period, animals were exposed to a simulated altitude of 8,000 ft (barometric pressure 564 torr), followed by a second control period at ground level. Both experimental groups had similar values of PaCO2 at ground level and during exposure to reduced barometric pressure. The tidal volume necessary to maintain eucapnia was higher in oleic acid-injured animals compared with the control group; cardiac output and functional residual capacity were lower. The alveolar-arterial oxygen difference was substantially larger in the oleic acid group. Adequate gas exchange can be maintained with HFO during exposure to altitude provided that ventilation and inspired PO2 are not reduced below normobaric levels. PMID- 2225897 TI - Effects of clinical maneuvers on sonographically determined internal jugular vein size during venous cannulation. AB - We sought to define variations in internal jugular vein (IJV) anatomy and the effect of recommended cannulation maneuvers on a population of ICU patients. Maneuvers that decreased IJV lumen cross-sectional area were carotid artery palpation (1.48 to 0.82 cm2, p less than .05) and advancement of the needle (1.57 to 0.75 cm2, p less than .001). The head-down (modified Trendelenburg) position increased IJV lumen cross-sectional area (1.18 to 1.62 cm2, p less than .05). There was wide variability in IJV anatomic features, although most patients had patent veins. PMID- 2225898 TI - Stroke volume measurements by electrical bioimpedance and echocardiography in healthy volunteers. AB - To evaluate the validity of three equations for estimation of thoracic electrical field size in a new bioimpedance algorithm, stroke volume (SV) as calculated by these equations was compared with that calculated by Doppler echocardiography in 48 healthy volunteers, both lean and obese. When the volume of electrically participating tissue was estimated from body height (modified Sramek) or body height corrected for body habitus (Sramek-Bernstein), there was considerable variation between bioimpedance and Doppler stroke volumes. When the volume of electrically participating tissue was estimated from the actual measurement of the height of the thorax and the circumference at the base of the thorax, the variation in SV differences decreased substantially (Sramek equation), although still considerable for clinical use, and there was no relationship between SV thus obtained and body habitus. Analysis of calculated stroke indices derived by our Doppler echocardiographic standard, as compared with values in the literature, revealed a systematic underestimation. We conclude that the original Sramek equation systematically underestimates SV by 15% to 20%, and the modified Sramek and Sramek-Bernstein equations systematically underestimates SV by 15% to 20%, and the modified Sramek and Sramek-Bernstein equations systematically overestimate SV in females by about 15%, but provide SV values in males in the predicted range. Further studies on the current assumption that the electrical field size is a truncated cone may improve precision of the bioimpedance method. PMID- 2225899 TI - Use of a palatal stabilizing device in prevention of palatal grooves in premature infants. AB - A prospective, randomized study using an acrylic palatal stabilizing device (PSD) was conducted to evaluate the effectiveness of this device in preventing disruptions in palatal architecture. A total of 26 premature infants with birth weights of 540 to 1740 g, and intubated orally for a period varying from 7 to 109 days were randomized to control and experimental groups. All neonates in the control group developed palatal grooving ranging from 2 to 5 mm in depth, whereas those in the experimental group (with a PSD) showed no evidence of palatal grooving. We conclude that a PSD is an effective preventive device in premature orally intubated infants. PMID- 2225900 TI - National estimates of intensive care utilization and costs: Canada and the United States. AB - Although ICUs generate attention as consumers of resources, no national data on utilization and costs were available in Canada. U.S. estimates are too old for current comparison. Based on national hospital survey data from Statistics Canada, we calculated the utilization of ICUs in all Canadian general hospitals from 1969 to 1986 and estimated costs for 1986. Using the American Hospital Association's Annual Survey, we estimated comparable trend data from U.S. hospitals for the period of 1979 to 1986, and national ICU costs for 1986. The results demonstrated steady growth in Canadian utilization from 1969 to 1986, with increased ICU patient days (17 to 42 days/1000 population). National costs for 1986 were estimated at $1.03 billion (Canadian), which was roughly 8% of total inpatient costs and 0.2% of Canada's gross national product (GNP). Utilization trend data for the United States showed a rapid increase from 1979 through 1982 with slower growth after that. In the United States, ICU utilization in 1986 was estimated at 108 patient days/1000 population. Total ICU costs were estimated at $33.9 billion (U.S.), which is 20% of all inpatient hospital costs and accounts for 0.8% of the GNP. ICU utilization in the United States is 2.5 times that of Canada. PMID- 2225901 TI - Pneumocephalus caused by a nasopharyngeal oxygen catheter. PMID- 2225902 TI - Chemoreceptor injury as probable cause of respiratory depression after a simultaneous, bilateral carotid endarterectomy. PMID- 2225903 TI - Use and abuse of the balloon tip pulmonary artery (Swan-Ganz) catheter: are patients getting their money's worth? PMID- 2225905 TI - Is the timing of intensive care unit admission important? PMID- 2225904 TI - Acquired immunodeficiency syndrome and critical care. PMID- 2225906 TI - Critically ill polyneuropathy and weaning failure. PMID- 2225907 TI - Use of survivors' cardiorespiratory values as therapeutic goals in septic shock. PMID- 2225908 TI - Comparison of two impedance cardiographic techniques for measuring cardiac output in critically ill patients. PMID- 2225909 TI - Succinylcholine and atropine for premedication of the newborn infant before nasotracheal intubation: randomized, controlled trial. PMID- 2225910 TI - Cold denaturation of proteins. AB - This article summarizes all experimental facts concerning the cold denaturation of single-domain, multi-domain, and multimeric globular proteins in aqueous solutions with and without urea and guanidine hydrochloride. The facts obtained by various experimental techniques are analyzed thermodynamically and it is shown that the cold denaturation is a general phenomenon caused by the very specific and strongly temperature-dependent interaction of protein nonpolar groups with water. Hydration of these groups, in contrast to expectations, is favorable thermodynamically, i.e., the Gibbs energy of hydration is negative and increases in magnitude at a temperature decrease. As a result, the polypeptide chain, tightly packed in a compact native structure, unfolds at a sufficiently low temperature, exposing internal nonpolar groups to water. The reevaluation of the hydration effect on the base of direct calorimetric studies of protein denaturation and of transfer of non-polar compounds into water leads to revision of the conventional conception on the mechanism of hydrophobic interaction. The last appears to be a complex effect in which the positive contributor is van der Waals interactions between the nonpolar groups and not the hydration of these groups as it was usually supposed. PMID- 2225911 TI - RATG: implications for nursing care in organ transplantation. AB - Proper immunosuppression is a key element determining the survival of patients undergoing organ transplantation. RATG is one of several immunosuppressive agents available for use. Nurses need to recognize the unique challenges that RATG poses for patient and dosage preparation, along with those affecting its administration and post administration. Doing so can effectively aid the transplanted patient in achieving optimal immunosuppression with the least amount of unpleasant effects. The hospital stay for a transplant patient can be very frustrating and exhausting. Nursing interventions that limit these effects can foster a more desirable patient experience. PMID- 2225912 TI - Insulinoma: diagnosis and treatment. AB - A patient with an insulinoma, although rare, can be an interesting challenge to the critical care nurse. Recognition of signs and symptoms pointing to possible insulinoma is vital to prevent delays in appropriate treatment. Intensive nursing care is necessary in the preoperative, intraoperative, and postoperative stages of this condition. PMID- 2225913 TI - Effect of lead selection on atrial-paced rhythm. PMID- 2225914 TI - ANA policies regarding HIV disease. PMID- 2225915 TI - Care plan for the patient undergoing intracardiac myxoma excision. PMID- 2225916 TI - Acute esophageal bleeding and endoscopic injection sclerotherapy. AB - Endoscopic injection sclerotherapy in the critical care setting is a recently developed method for controlling bleeding from esophageal varices. Since this therapy is often employed as an emergency measure, nurses in ERs and ICUs should be familiar with the procedure. The enclosed outline can be modified to fit the needs of individual physicians, units, and institutions. PMID- 2225917 TI - Postoperative care of the renal transplant patient. PMID- 2225918 TI - Critical care nursing in the 21st century. AB - This paper has explored some of the major trends that we can anticipate encountering as we enter the 21st century. Critical care nurses who wish to participate proactively in shaping their professional destiny will listen closely to what futurists have to say about life in the decades ahead. The more we know about what to anticipate, the more informed our decisions will be, and the more likely we will make our desired future a reality. PMID- 2225919 TI - Dual-chamber update. PMID- 2225920 TI - People and environment protected from medical sharps with new disposal system. PMID- 2225921 TI - Bladder cancer. AB - Bladder cancer is largely a preventable disease; epidemiologic studies indicate that the majority of cases occur as a result of cigarette smoking or occupational exposures. The impact of screening high-risk populations is uncertain, but prompt and early diagnosis is essential for optimal therapeutic results. The management of different stages of disease varies greatly and is currently in a state of evolution. The majority of cancers are superficial, of low malignant potential, and can generally be treated cystoscopically. Few studies have addressed whether intravesical therapy will prevent high-risk patients with superficial disease from developing muscle invasion or distant metastases. Controversy exists as to optimal management of patients with invasive cancers. Improvements in technique and methodologies of urinary diversion have made cystectomy more tolerable for patients. Although cystectomy remains the "gold standard," probably not all patients require it. The careful selection of those patients whose bladders can be preserved is currently being evaluated. Combination chemotherapy for patients with metastatic bladder cancer is very active, appears to prolong survival, and may offer durable remissions to some patients. Whether chemotherapy will permit greater numbers of patients with invasive bladder cancer to be cured and bladders preserved remains to be determined. PMID- 2225922 TI - Neurologic conditions affecting the cardiovascular system. PMID- 2225923 TI - Sexual abuse of children. PMID- 2225924 TI - Inaugural address. PMID- 2225925 TI - A dermatologic diary. Portrait of a practice. PMID- 2225926 TI - The management of eyelid dermatitis in patients with "status cosmeticus": the cosmetic intolerance syndrome. PMID- 2225927 TI - Recent developments in sexually transmitted diseases: is heterosexual transmission of human immunodeficiency virus a major epidemiologic factor in the spread of acquired immunodeficiency syndrome? III: AIDS in Sub-Saharan Africa. PMID- 2225929 TI - Epilation. AB - An ancient manual technique of epilation still in common usage, and modern electrical epilating devices, are compared. Folliculitis may occasionally be produced by either type of procedure. PMID- 2225928 TI - Swimmer's itch: a cercarial dermatitis. PMID- 2225930 TI - Lobomycosis (keloidal blastomycosis): case reports and overview. AB - Lobomycosis is a deep fungal disease of the skin without involvement of internal organs or mucous membranes. The disease is characterized by skin nodules and plaques resembling keloid involving the earlobes, distal parts of the upper and lower extremities, and buttocks. In severe cases, large skin areas can be covered by disseminated or grouped and confluent nodules. Most cases are reported from South and Central America. The fungus Paracoccidioides (Glenosporella) loboi is abundant in lesions but is extremely difficult to culture. Lobomycosis is resistant to chemotherapy, but in some cases it can successfully be treated by excision. Although the diagnosis is easily established by its typical clinical, histologic, and microbiological features, it is often misdiagnosed by physicians not familiar with the disease. We describe here five patients and present an overview of this rare disease. PMID- 2225931 TI - Incarceration for excoriation. AB - A thirty-six-year-old man experienced acute, severe, generalized pruritus. His scratching was erroneously interpreted as lewd and indecent behavior. He was arrested. Results of the history and physical examination led to the diagnosis of fiberglass dermatitis, which prompted a dismissal of the charges. Although many societies have looked askance at persons with certain skin diseases (such as leprosy) and at scratching in public since at least biblical times, we are not aware of any prior reports of incarceration for excoriation. PMID- 2225932 TI - Noonan's syndrome with extensive verrucae. AB - We report the case of a patient with multiple findings characteristic of Noonan's syndrome, including a severe lymphedema present since early infancy, hypertelorism, low-set and prominent ears, broad facies, low posterior hairline, high arched palate, broad short neck, slightly short stature, and moderate dental malocclusion. In addition, extensive verrucae planae, verrucae vulgares, and condylomata acuminata occurred and were refractory to conventional therapy. To our knowledge, this is the first report of an association of Noonan's syndrome with extensive verrucae. We speculate that it is related to immunodeficiency as a consequence of loss of immunoglobulins and lymphocytes from intestinal lymphangiectasia. Cutaneous findings and other physical anomalies reported in patients with Noonan's syndrome are reviewed. PMID- 2225933 TI - Tumefactive amyloidosis: a plantar pedal presentation. AB - Tumefactive or nodular amyloidosis represents an uncommon variant of the disease. Localized tumorous masses, which are lardaceous in appearance, rubbery in texture, and approaching several centimeters in diameter, typify the presentation. Such lesions pose unique problems when situated on the weight bearing regions of the plantar foot. The author discusses the use of accommodative weight-dispersing insoles as an alternative to surgical excision for the treatment of such lesions. PMID- 2225934 TI - Vitiligo and pernicious anemia presenting as congestive heart failure. AB - The skin often provides diagnostic clues to systemic disorders. Vitiligo is an acquired disease characterized by depigmentation of the skin due to destruction of melanocytes. Vitiligo may be an autoimmune disease and is associated with other disorders that may also arise due to autoimmune mechanisms. We present the unusual case of vitiligo associated with pernicious anemia in a patient who presented to the hospital because of hyperdynamic congestive heart failure. PMID- 2225935 TI - Impact of pretreatment (imprinting) with insulin on insulin-induced mitotic activity in Chang and CHO cell lines. AB - Primary interaction with insulin increased the mitotic activity of Chang liver and Chinese hamster ovary (CHO) cells. Re-exposure to insulin accounted for a significant increase of mitoses over the control, but for a considerable decrease thereof relative to the effect of primary exposure. The hormone had a more pronounced effect on its direct target cells (Chang liver cells) than on the CHO cells. PMID- 2225936 TI - A further study on the regulation of microbial proteases. AB - Various agents were tested for their effects on microbial proteases, which activity was monitored by the analysis of cleaved peptide bands in SDS polyacrylamide gel electrophoresis. Using casein as a substrate, fungal protease (type XIX) was inhibited by the phenyl methyl sulphonyl fluoride, chymostatin, antipain and leupeptin, while bacterial protease (type XXVI) was inhibited by phosphatidyl glycerol, phosphatidyl inositol and sphingosine. MS2 RNA exerted minor inhibition on the bacterial proteolysis of regulatory subunits of cyclic AMP-dependent protein kinase (A-PK). The cleavage of DNA binding protein by both proteases was inhibited, in the presence of MS2 RNA and lambda DNA. In comparison, phosphatidyl serine slightly stimulated the fungal protease on the cleavage of ribonuclease T1. RNA polymerase is a good substrate of the bacterial protease as indicated by the generation of multiple cleaved peptide fragments, whereas alkaline phosphatase is not susceptible to proteolysis. PMID- 2225937 TI - Percutaneous tracheostomy. A cautionary note. PMID- 2225938 TI - Take a doctor to dinner. PMID- 2225939 TI - Tuberculosis in the time of AIDS. The facts and the message. PMID- 2225940 TI - Angiotensin-converting enzyme inhibitors and cough. PMID- 2225941 TI - Hepatopulmonary syndrome. PMID- 2225942 TI - Thermodilution right ventricular ejection fraction. Remaining questions. PMID- 2225943 TI - Undiagnosed tuberculosis in patients with human immunodeficiency virus infection. AB - We describe the clinical features of 11 patients with human immunodeficiency virus infection in whom tuberculosis was undiagnosed and untreated prior to death. Most patients (9 of 11) had pulmonary complaints and 8 of 11 had roentgenographic findings suggestive of tuberculosis (hilar or mediastinal adenopathy, pleural effusion, apical infiltrate or miliary pattern). Despite these findings, tuberculin skin tests were not performed in any of the patients. Acid-fast smears of sputum were obtained in three cases and bronchoscopy performed in only four, reflecting the low index of suspicion for tuberculosis. Pneumocystis carinii pneumonia was the presumptive diagnosis in nine cases but was confirmed in only one case. Autopsy revealed tuberculosis as the cause of death in four patients. Of the seven patients who did not undergo autopsy, disseminated tuberculosis, manifest by mycobacteremia, was the only life threatening illness identified and probably contributed to death. Increased awareness of the clinical and roentgenographic features of tuberculosis in HIV infected patients, combined with more intensive use of acid-fast smears and tuberculin skin testing, are necessary in order to decrease mortality from this treatable complication of HIV-infection. PMID- 2225944 TI - Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS. AB - Forty-eight patients with disseminated cryptococcosis and AIDS were retrospectively studied to define the pulmonary manifestations. Cryptococcus neoformans (CN) was first isolated from a pulmonary site in 12 patients. Disseminated disease was subsequently documented in all these patients. Symptoms and roentgenographic manifestations (normal, nodular/circumscribed infiltrates, pleural effusions, lobar consolidation) were diverse. Interstitial infiltrates predicted the presence of another opportunistic lung infection besides cryptococcosis in five patients (three untreated and two treated patients). Infectious causes other than cryptococcosis were established by culture and clinical course in five of the ten patients who developed chest roentgenographic abnormalities during amphotericin B therapy. Endobronchial abnormalities were identified in four patients at bronchoscopy. Bronchoalveolar lavage (9/9) and pleural fluid (3/3) cultures were sensitive tests for detection of pulmonary involvement with CN. PMID- 2225945 TI - Mortality from pulmonary embolism in the United States: 1962 to 1984. AB - To examine the effect of advances in the prevention of and therapy for PE, we reviewed mortality for PE in the United States from 1962 to 1984. Age-adjusted PE mortality increased by 67 to 100 percent between 1962 and 1974 for white and non white men and women. From 1975 to 1984, these rates declined by 20 to 28 percent. Non-white PE mortality was greater than white PE mortality; men had a greater risk of PE death than women. Age-specific patterns (more than 40 years of age) of PE mortality followed those of the age-adjusted death rates, with increases noted in all groups between 1962 and 1974 and declines during the 1975-1984 period. These patterns might reflect improved ascertainment of cases and better prevention of disease. The magnitude of the rates suggests that the list of indications for prophylactic anticoagulation should be re-examined for possible expansion. PMID- 2225946 TI - Exercise performance of polycythemic chronic obstructive pulmonary disease patients. Effect of phlebotomies. AB - The purpose of this study was to determine the effects of phlebotomy on the exercise tolerance and right and left ventricular ejection fraction of polycythemic patients with chronic obstructive pulmonary disease. Ten patients with COPD (mean FEV1 = 1.32 +/- 0.55 L) and polycythemia (mean Hct = 62 +/- 3 percent) were studied before and after their hematocrits had been reduced to approximately 50 percent. Post-phlebotomy the maximal oxygen consumption increased from 1.09 +/- 0.34 L/min to 1.26 +/- 0.43 L/min (p less than 0.05) and the maximum workload increased from 56.5 +/- 32.6 watts to 74.5 +/- 23.4 watts (p less than 0.05). The increase in the exercise tolerance appeared to be primarily due to an increased cardiac output at Emax. There was no relationship between the increases in the upright exercise capacity and changes in the supine ejection fractions of the right or left ventricular either at rest or during exercise. PMID- 2225947 TI - Computed tomography in patients with esophageal perforation. AB - Contrast esophagram is the diagnostic procedure of choice in patients with clinically suspected perforation of the esophagus. In patients in whom the usual clinical signs or symptoms are unrecognized and in whom the diagnosis is obscure, the diagnosis of a perforated esophagus may be suggested by the finding of mediastinal fluid and air on CT. Three patients are reviewed. The perforations included one spontaneous, one from erosion of an esophageal carcinoma, and one iatrogenic. In two of the three patients, the diagnosis of perforated esophagus had not been made initially and in one patient the initial esophagram was interpreted as normal. Computed tomography of the chest in each patient led to the suspected diagnosis of perforated esophagus. Prompt appropriate surgical intervention followed. The findings of mediastinal fluid and more importantly mediastinal air on CT of the chest are strongly suggestive of esophageal perforation. PMID- 2225948 TI - Quality of well-being before and after antibiotic treatment of pulmonary exacerbation in patients with cystic fibrosis. AB - General quality of life has only recently been measured with an objective tool in patients with cystic fibrosis (CF), and there have been no reported attempts to document changes in patients' overall well-being over time, as patients deteriorate or respond to intervention. We applied the Quality of Well-Being scale (QWB) in 28 patients with CF before and after a two-week course of oral ciprofloxacin used to treat pulmonary exacerbations. There were significant correlations between changes in QWB and various pulmonary function test results; QWB vs FEV1: r = 0.4, p less than 0.03; QWB vs FVC: r = 0.5, p less than 0.01; and QWB vs SaO2: r = 0.4, p less than 0.05. Thus, the QWB can track changes in general well-being in CF patients over a brief time and detect changes associated with pulmonary exacerbation and its treatment. PMID- 2225949 TI - Bronchial hyperreactivity in patients with mitral valve disease. AB - To elicit the mechanism of bronchial hyperreactivity (BHR) in chronic heart failure (CHF), a methacholine inhalation test, pulmonary function test, and cardiac catheterization were performed in 19 patients with mitral valve disease (MVD), and the change of severity of BHR before and after mitral valve replacement (MVR) was also examined in seven of 19 patients with MVD. Sixteen of 19 patients with MVD showed significant increase in respiratory resistance in methacholine inhalation test, while all normal subjects did not. The maximal expiratory flow at 25 percent of vital capacity (Vmax25), a parameter of small airway disease, correlated significantly with log cumulative dose producing a 35 percent decrease in respiratory conductance (PD35Grs) (r = 0.536) and the duration of symptoms (r = -0.682). There was a significant correlation between log PD35Grs and mean pulmonary artery wedge pressure (r = -0.466). After MVR, log PD35Grs was significantly improved in all seven operated-on patients, although six patients retained BHR. We conclude that patients with long-term MVD have marked BHR and that BHR in long-term MVD is related to peripheral airway narrowing with organic remodeling, which was not ameliorated with MVR procedure, in addition to pulmonary congestion. PMID- 2225950 TI - Respiratory muscle strength in congestive heart failure. AB - In experimental animals, conditions which drastically decrease cardiac output may reduce the strength and endurance of respiratory muscles leading to hypercapnic respiratory failure. Because patients with chronic CHF have reduced cardiac output and vital capacity (FVC), we measured PImax and PEmax and maximal handgrip force in 16 patients with CHF and 18 AMNs. The patients with CHF had a mean left ventricular ejection fraction of 26 +/- 7 percent. Maximal respiratory pressures were significantly reduced; group mean values (+/- SD) for PImax at FRC were 41.4 +/- 5.6 cm H2O (CHF) and 102.1 +/- 27.4 cm H2O (AMN) (p less than 0.001), with PImax values in five patients with CHF as low as 20 to 30 cm H2O. In most patients, PEmax was comparably reduced. Handgrip force was less dramatically reduced, suggesting selective respiratory muscle weakness. Possible explanations include reduction in respiratory muscle blood flow or generalized muscular atrophy and weakness related to cardiac cachexia. PMID- 2225951 TI - Comparison of aerosolized glycopyrrolate and metaproterenol in acute asthma. AB - The efficacy of nebulized glycopyrrolate compared with metaproterenol was evaluated in 46 patients with acute asthma. In a double-blinded, randomized fashion, patients received, as sole therapy, either 2 mg of glycopyrrolate or 15 mg of metaproterenol every 2 h over a 6-h study period. Of the 35 patients completing the study, analysis of variance demonstrated no difference in percentage of change in FEV1 between glycopyrrolate and metaproterenol. Two hours after the initial dose, there was a 30 percent increase in FEV1 for glycopyrrolate compared with a 25 percent increase for metaproterenol (p greater than 0.05, NS). In contrast to the comparable bronchodilator activity, the side effects profile of the two agents were markedly dissimilar. Not only were subjective complaints of tremor, palpitations, and paresthesias increased for metaproterenol, but the heart rate response was significantly elevated (p less than 0.05) compared with glycopyrrolate. Based on these data, administration of the aerosolized anticholinergic agent, glycopyrrolate, is a reasonable therapeutic alternative for acute asthma. PMID- 2225952 TI - Myocardial revascularization for the third time. Clinical characteristics and follow-up. AB - Twenty-five patients presenting for a third revascularization procedure were retrospectively reviewed at Loyola University Medical Center, Maywood, IL. This represents 0.5 percent of the total revascularization cases over a five-year period extending from 1985 through 1989. Perioperative mortality was none, and seven complications occurred in six patients. Internal mammary arteries were used for revascularization in 60 percent of this group. Follow-up reveals that only one patient has died secondary to an arrhythmia. All patients except one are symptomatically improved, and 18 patients remain angina free at a mean follow-up of 22.3 months. It is therefore concluded that patients are clinically improved with a third revascularization, and this procedure should be offered as an effective means of treatment. PMID- 2225953 TI - The effects of phenylephrine on right ventricular performance in patients with pulmonary hypertension. AB - Pulmonary hypertension causes right ventricular ischemia and failure as a result of increased afterload combined with reduced coronary blood flow. Increasing coronary driving pressure by raising aortic pressure with phenylephrine has been shown to reverse right ventricular ischemia from pulmonary hypertension in animals. Since vasodilators often fail to reduce afterload, we tested whether raising the coronary driving pressure would improve right ventricular function in man. Ten patients with pulmonary hypertension had hemodynamics and right ventricular coronary driving pressure measured before and 10 minutes after a steady state was reached with a phenylephrine infusion titrated to raise aortic pressure by 25 percent. Phenylephrine caused a significant (p less than .01) increase in mean aortic pressure (84 to 108 mm Hg) and right ventricular coronary driving pressure (46 to 69 mm Hg). In response, there was a significant (p less than .01) rise in mean pulmonary artery pressure (58 to 67 mm Hg), right ventricular end-diastolic pressure (10 to 16 mm Hg) and wedge pressure (5 to 9 mm Hg), and an insignificant fall in cardiac output (3.26 to 3.09 L/min) and pulmonary artery O2 saturation (57 to 49 percent). Although phenylephrine increased right ventricular coronary driving pressure, it worsened right ventricular function as manifest by a rise in end-diastolic pressure and fall in cardiac output. Any benefit of raising right ventricular coronary driving pressure may have been offset by alpha vasoconstriction of right ventricular coronary blood flow and/or pulmonary arterial vasoconstriction. Phenylephrine does not appear to be a useful therapy of right ventricular failure from pulmonary hypertension in patients who fail vasodilators. PMID- 2225954 TI - Single lung transplantation for primary pulmonary hypertension. AB - Single lung transplantation has become a therapeutic option for end-stage interstitial lung disease and obstructive lung disease. Our group recently extended this treatment to three patients with primary pulmonary hypertension. All patients had marked decreases in pulmonary artery pressures and pulmonary vascular resistance and increases in cardiac output following single lung transplantation. Spirometry, lung volumes, and diffusion capacity were not different in comparison to preoperative studies. Quantitative ventilation perfusion scans revealed the majority of perfusion distributed to the transplanted lung, with ventilation approximately equally divided between the native and the transplanted lung. Despite ventilation-perfusion imbalance, there was no resting hypoxemia and there was no arterial oxygen desaturation with exercise. One patient expired on the 30th postoperative day due to cytomegalovirus infection of the lungs. In the remaining two patients, maximum exercise capacity following transplantation was near normal in one recipient and reduced in the second recipient. Of note, there was no evidence of ventilatory limitation or impaired oxygenation during exercise in these two recipients. Although an exaggerated exercise ventilatory response was present, this did not limit exercise performance. This report supports the use of single lung transplantation for the treatment of primary pulmonary hypertension. PMID- 2225955 TI - Subpleural mononuclear cell infiltration. Significance in the differential diagnosis of pleuritis showing nonspecific histologic findings. AB - To determine if patients who had lymphocyte-rich pleural effusion and a pleural biopsy without any specific findings could be histopathologically differentiated between those with tuberculous and nontuberculous pleuritis, we histologically re evaluated the pleural biopsies of all patients whose pleural effusion was predominant with lymphocytes and contained no malignant cells. A total of 40 patients with a nonspecific histologic findings of pleural biopsy specimen were categorized based on their ultimate diagnosis as having tuberculous (n = 15), carcinomatous (n = 10) or nontuberculous, benign pleuritis (n = 15). The pleural biopsy specimen of patients with nontuberculous, benign pleuritis frequently showed a band-like infiltration of mononuclear cells in the subpleural adipose tissue with minimal pleural inflammatory infiltrate (10 out of 15 patients), while the same finding was infrequent in those with tuberculous pleuritis (0 out of 15, p = 0.0001) and pleuritis associated with carcinoma (three out of 10, p = 0.082). Based on these results, the presence of band-like infiltration of mononuclear cells in the subpleural adipose tissue with minimal pleural inflammatory infiltrate in pleural biopsy specimens of patients with lymphocyte rich pleural effusion suggests that the pleuritis is nontuberculous in its nature. PMID- 2225956 TI - Bronchial cartilage alterations in lung transplantation. AB - Changes in the hyaline cartilage of the proximal bronchial tree were investigated in a group of combined heart-lung and double-lung recipients with and without OB. Ossification, calcification and fibrovascular ingrowth into the normally avascular hyaline bronchial cartilage were observed in almost all patients and were independent of small or large airway inflammation. Alterations in the integrity of hyaline cartilage have been produced by others in animals by ligation of the blood supply. Finding similar changes in airway cartilage of all transplanted lungs argues that there is relatively poor perfusion to the proximal air-conducting passage. Such a mechanism may contribute to the development of OB, bronchiectasis and a predilection for infections following pulmonary transplantation. PMID- 2225957 TI - Hyperresponsiveness of the extrathoracic airway in patients with captopril induced cough. AB - It has been suggested that cough from captopril may originate from an increased sensitivity of receptors in the extrathoracic airway (EA). To explore this hypothesis, we assessed the responsiveness of EA and bronchi and the cough sensitivity to inhaled histamine in nine hypertensive patients with captopril induced cough (group 1) during treatment and one month after withdrawal of the drug treatment. Nine patients who were asymptomatic while receiving captopril (group 2) and nine patients receiving no current treatment (group 3) served as controls. The EA responsiveness was assessed by using the maximal midinspiratory flow (MIF50) as an arbitrary index of EA constriction and was expressed as the histamine concentration causing a 25 percent decrease in MIF50 (PC25MIF50). PC15FEV1 was the index of bronchial responsiveness and PCcough (dose causing five or more coughs) was that of cough sensitivity. Airway hyperresponsiveness (EA-HR or BHR) was diagnosed when PC25MIF50 or PC15FEV1 were 8 mg/ml or lower. Patients with captopril-cough, as compared with controls, had significantly lower values of PC25MIF50, PC15FEV1, and PCcough; EA-HR and BHR were found, respectively, in seven and three of these patients and in none of the control subjects. In all the patients of group 1, cough and EA-HR resolved after withdrawal of captopril treatment, while BHR persisted in one. PC25MIF50, PC15FEV1, and PCcough were all significantly improved. Our findings suggest that cough during captopril therapy may originate from receptors in the EA. PMID- 2225958 TI - Cardiopulmonary assessment in beta-thalassemia major. AB - Thalassemia patients succumb at a young age to congestive heart failure. Hitherto, attention has been focused on left ventricular function. This report emphasizes right ventricular dysfunction and abnormal pulmonary function. We performed cardiopulmonary evaluation, including echo-Doppler, spirometry, CO diffusion (DCO), and blood gas analyses in 35 patients with homozygous beta thalassemia maintained by multiple blood transfusions. Six autopsy lung specimens were studied. Thalassemia patients exhibited pulmonary dysfunction, characterized by hypoxemia (85 percent of the patients were outside the 95 percent confidence limits), reduced lung volumes (51 percent), flow rates (63 percent) and DCO (50 percent). Right ventricular dysfunction was more prevalent than left ventricular dysfunction. Furthermore, 75 percent of the patients had evidence of pulmonary hypertension consistent with more frequent right ventricular rather than left ventricular dysfunction. Our findings suggest that in thalassemia patients, complex cardiopulmonary abnormalities precede the final outcome of congestive heart failure. PMID- 2225959 TI - The entrainment of low frequency breathing periodicity. AB - It has been predicted by mathematical models of the respiratory control system that the delay between the lung and the respiratory controller may determine the cycle time found in periodic breathing. We examined cycle time of periodic breathing and circulation time in 11 patients known to have circulation delay due to heart failure. We did not find a significant relationship between the amount of periodic breathing and circulation delay, but found a very high correlation between circulation delay and the cycle time of periodic breathing (r2 = 0.825; p = 0.0001). PMID- 2225960 TI - Feasibility of intraoperative cytodiagnosis of lung cancer. AB - Of 354 thoracotomies, 114 cases involved intraoperative cytopathologic evaluation. The study included 86 men and 28 women, and 184 specimens were examined. Smears were taken from the lung lesion or lymph node and the chest wall or bronchial stump by imprint or needle aspiration. Intraoperative evaluations were compared with histologic findings. In 85 cases not diagnosed as malignant preoperatively, malignancy was confirmed in 97.6 percent of cases and histologic type in 71.8 percent. In the 28 cases diagnosed as malignant preoperatively, there was only one false-negative. The most important finding during thoracotomy is whether a lesion is malignant or not. The time required to obtain a pathologic diagnosis also is important. We are able to obtain the results of a cytologic diagnosis within 10 min. Cytologic diagnosis of malignancy during thoractomy may be a feasible and convenient method of diagnosis, especially where malignancy is suspected. PMID- 2225961 TI - Concentration of tumor-associated trypsin inhibitor (TATI) in pleural effusions. AB - We measured the concentration of tumor-associated trypsin inhibitor (TATI) in plasma and pleural fluid of 84 patients with pleural effusions of various causes. We observed elevated (greater than 30 micrograms/L) TATI levels in pleural fluid in 45 percent of patients with pleural effusion associated with malignant disease and in 15 percent of patients with benign disease. Similar results were obtained for TATI in plasma. The concentration of TATI in pleural fluid closely parallelled that in plasma. In patients with renal insufficiency and in patients with biliary obstruction, the TATI levels were elevated both in plasma and pleural fluid. A positive correlation was seen between the concentration of TATI and the activity of alkaline phosphatase in plasma. The results show that simultaneous determination of TATI in plasma and pleural fluid improves the diagnosis of cancer only marginally. Our results also support the hypothesis that elevated TATI levels may reflect an acute phase reaction caused by inflammatory disease or tissue destruction associated with cancer not only in inflammatory conditions, but also in malignant disease where the tumor itself is not producing TATI. PMID- 2225962 TI - Progressive functional deterioration of bioprostheses assessed by Doppler ultrasonography. AB - Doppler echocardiography was used to study the function of bioprosthetic heart valves by noninvasive means in 32 patients aged 29 to 72 years at various postoperative intervals. There were 24 Ionescu-Shiley, four Hancock, and four Carpentier-Edwards prostheses, 19 in the aortic and 13 in the mitral position. Initial studies were performed at a mean of 2.3 years after implantation and were repeated one, two, and three years thereafter. Flow velocities in the mitral orifice, left ventricular outflow tract, and ascending aorta, as well as mitral pressure half-time, were measured from pulsed-wave or continuous-wave Doppler recordings. Mitral and aortic valve areas and aortic pressure gradients were calculated. In aortic prostheses the valve area decreased and pressure gradient increased progressively in relation to the time from implantation. The mean value (+/- SD) of the aortic valve area was 67 +/- 17 percent of the manufacturer's nominal value at the first examination and 57 +/- 20 percent one year later, 51 +/- 14 percent two years later, and 46 +/- 11 percent three years later (overall differences, p less than 0.01). In mitral prostheses, reduction of the valve area was not related to the time from implantation. The mean mitral valve area was 45 +/- 12 percent of the nominal value at rest and increased to 68 +/- 18 percent during exercise at a mean of 45 months after implantation. There was no change in these values at the one-year repeat study. It is concluded that in a population with predominantly pericardial bioprostheses, (1) aortic tissue prostheses showed a progressive functional deterioration demonstrable by Doppler echocardiography, most probably due to degenerative changes; and (2) in mitral tissue prostheses, there was no significant reduction of orifice area in relation to time from implantation. Reduction of mitral valve areas may, to some extent, reflect a less than full opening at rest. PMID- 2225963 TI - Abnormal hemodynamic response to Valsalva maneuver in patients with atrial septal defect evaluated by Doppler echocardiography. AB - Hemodynamic responses to the Valsalva maneuver were studied in eight healthy subjects (group 1) and eight patients with ASD (group 2) using Doppler echocardiography. The acute changes of aortic blood flow profiles during the Valsalva maneuver were investigated on a basis of beat-to-beat estimation. During the active strain phase (phase 2), group 1 showed a significant decrease in systolic blood pressure, SV and CO with reflex tachycardia; in group 2, there was a significant decrease in SV and CO with reflex tachycardia, but not systolic blood pressure. The percentage decreases in SV and CO in group 2 were significantly less than those in group 1 (23 +/- 16 percent vs 48 +/- 10 percent for SV, p less than 0.01; 17 +/- 12 percent vs 40 +/- 13 percent for CO, p less than 0.05). After release of strain phase (phase 4), group 1 showed significant reversed changes in systolic blood pressure, SV and heart rate, indicating an overshoot effect which was, however, not observed in group 2. Thus, patients with ASD presented abnormal Valsalva response which was characterized by the absence of phase 4 overshoot and a less marked phase 2 change. The findings suggest that the decremental effect of impaired venous return on stroke output during active strain may be attenuated by the increased pulmonary blood volume due to left-to right shunt. In patients with ASD, the lesser decrement of CO during phase 2 may not provoke sufficient sympathetic activity to induce overshoot response in phase 4. PMID- 2225964 TI - Neural respiratory drive and neuromuscular coupling in patients with chronic obstructive pulmonary disease (COPD). AB - In 15 spontaneously breathing patients with chronic obstructive pulmonary disease (COPD) divided into two groups, one with normocapnia (A) and one with chronic hypercapnia (B), we evaluated the maximal voluntary inspiratory muscle strength (MIP), the pattern of breathing, the mouth occlusion pressure (Po.1), the neural respiratory drive (NRD), assessed by surface electromyographic (EMG) activity of the diaphragm (EMGd) and EMG activity of intercostal muscles (EMGint), and the chest wall neuromuscular coupling, assessed in terms of Po.1/EMGd ratio. Compared with an age-matched normal control group, both A and B groups exhibited lower MIP, significantly greater EMGd and EMGint, and lower Po.1/EMGd ratio. However, a similar pattern, along with a rapid and shallow breathing, differentiated group B from group A. In group B we found a significant direct relationship between Po.1/EMGd ratio and MIP, and an inverse relationship between PaCO2 and Po.1/EMGd ratio. These data seem to indicate the following: (1) EMG is a more precise method than Po.1 in assessing the magnitude of the NRD; (2) NRD is increased in these patients; and (3) clinical manifestations probably associated with inspiratory muscle fatigue (marked decrease in muscle strength, rapid and shallow breathing, and alveolar hypoventilation) may be accompanied by a greater NRD and a more marked derangement in chest wall neuromuscular coupling in COPD. PMID- 2225965 TI - Real and pseudo late asthmatic reactions after submaximal exercise challenge in patients with bronchial asthma. A new definition for late asthmatic responses after exercise challenge. AB - The late asthmatic reaction after exercise challenge remains a controversial issue. In this study, 21 patients recorded peak expiratory flow rate (PEFR) on two control days without performing exercise. There was no difference between both control days when PEFR at 1 h was compared with baseline PEFR and when PEFR at 4 to 13 hours was compared with baseline PEFR. After analyzing variation coefficients of baseline PEFR on a control day and exercise day, PEFR was not allowed to differ more than 15.3 percent in the same patient when comparing exercise day and control day for the late fall in PEFR in the study. In 17 of 81 patients, a late asthmatic reaction after exercise challenge was present when PEFR fall was greater than or equal to 20 percent compared with baseline PEFR value. In eight of the 17 patients, a real late asthmatic reaction to exercise challenge was present with a PEFR fall greater than or equal to 20 percent on at least three successive time points and who had a PEFR fall greater than or equal to 20 percent compared with corresponding clocktime on a control day. The late asthmatic reaction to exercise challenge is characterized not as a nonspecific epiphenomenon, but as a fall in PEFR of greater than or equal to 20 percent compared with baseline PEFR value and with corresponding clocktime on a control day on at least three successive time points. Graphic illustration of airway responses following exercises may facilitate the detection of a late asthmatic response. PMID- 2225966 TI - Hemodynamic status in critically ill patients with and without acute heart disease. AB - Physicians have been urged to reduce the use of the pulmonary artery catheter. However, there are no guidelines to help the clinician make the decision to use or withhold invasive monitoring in the individual patient. This study was designed to examine the accuracy of physician estimates of cardiac function in a spectrum of patients with hemodynamic instability to determine whether differences in accuracy among subgroups would suggest subgroups of patients who could be managed without invasive measurements. Physician estimates of cardiac index were found to be sufficiently accurate in patients without acute heart disease that initial management without invasive monitoring may be appropriate in selected cases. However, due to the general inaccuracy of physician estimates, efforts to improve the accuracy of clinical judgments of cardiac function and hemodynamic status should be pursued with vigor in patients both with and without acute cardiac dysfunction. PMID- 2225967 TI - The impact of right ventricular infarction on the prevalence of ventricular arrhythmias during acute inferior myocardial infarction. AB - To determine the impact of RV infarction on the prevalence and complexity of ventricular arrhythmias during inferior AMI, 57 patients with no prior MI were studied by 24-hour Holter monitoring on the first and tenth days of AMI. Based on radionuclear studies, patients were allocated into two groups: (1) group A, 21 patients (37 percent) with normal RVEF (greater than or equal to 40 percent); and (2) group B, 36 patients (63 percent) with depressed RVEF (less than 40 percent). There were no significant differences between the groups regarding age and LVEF. Values of RVEF were 47 +/- 6 percent and 31 +/- 6 percent, respectively (p less than 0.05). The RVEF had no influence on the prevalence and complexity of early and late arrhythmias. Stratification of patients in group B into two subgroups based on the extent of RV dysfunction did not reveal any differences in the occurrence of all forms of ectopy (when both groups were matched to group A). Therefore, patients with inferior AMI, with or without RV infarction, have a similar prevalence of arrhythmias. Ventricular ectopic beats may be related to the severity and spread of LV involvement, rather than to RV dysfunction. PMID- 2225968 TI - Systemic hemodynamic and cardiac function changes in patients undergoing orthotopic liver transplantation. AB - The objective of this study was to determine the changes in systemic hemodynamics (systemic vascular resistance [SVR], cardiac output [CO], systemic blood pressure [SBP]) and cardiac function (pulmonary artery pressure [PAP] and pulmonary wedge pressure [PWP]) during the 96 hours following orthotopic liver transplantation (OLT) and correlate these with changes in hepatic and renal function and patient outcome. The study took place in a 12-bed medical respiratory intensive care unit in a large teaching hospital. Twenty-one patients had OLT performed over a 21.5 month period (January 1988 to October 15, 1989) for end stage liver disease (ESLD) from a variety of causes. A flow-directed right heart catheter and an indwelling arterial cannula were inserted for hemodynamic monitoring over a 96 hour postoperative period. Liver and renal function studies, total serum calcium, serum albumin, and fluid balance were determined daily. The SVR increased significantly to 12.8 +/- 0.6 U at 48 hours compared with immediate (less than 8 hours) postoperative levels (p less than 0.05) and remained elevated for 96 hours. The CO fell progressively and was significantly lower than baseline values from 64 to 96 hours. There was significant inverse correlation between the increase in SVR and the fall in CO (r = .85, p less than 0.01). The SBP was stable except for a small, but significant fall at 16 and 24 hours postoperatively. The PWP increased significantly from a baseline value of 12.5 +/ 0.9 mm Hg to 15 +/- 0.9 mm Hg at 32 hours and remained elevated through 96 hours (p less than 0.05). The serum bilirubin level fell progressively postoperatively and the prothrombin time and partial thromboplastin time (PTT) shortened significantly. Bile flow increased progressively from 107 +/- 120 ml/24 hours at the end of the first 24 hours to 188 +/- 125 ml/24 hours by 96 hours postoperatively. Five patients died from nine to 43 days postoperatively. These patients' hemodynamic parameters were not significantly different from the patients who survived. Successful OLT is associated with a rapid increase in SVR and a fall in CO without changes in SBP. These findings tend to parallel the improvement found in results of liver function tests. However, there is no correlation between the improvement in the hemodynamic state and long-term survival. PMID- 2225969 TI - Permeability pulmonary edema following lung resection. AB - The etiology of edema associated with pulmonary resection was investigated in five patients during the immediate postoperative period. Three patients received pneumonectomy while two patients had one lobe resected. All patients suffered from severe respiratory distress and had x-ray evidence of diffuse interstitial pulmonary edema within 12 hours of surgery. Hemodynamic data were obtained with radial and pulmonary artery catheters. Edema fluid was obtained along with blood samples for simultaneous determination of protein and albumin content. All patients studied had normal or high cardiac output, normal cardiac filling pressures, and edema fluid protein to serum protein ratio of 0.6 or greater suggestive of permeability changes contributing to edema fluid accumulation. Calculated shunt fraction exceeded 25 percent in all patients. Pulmonary edema has been noted in patients following pulmonary resection in the early postoperative period. In patients reviewed here, two factors appeared to be significant. First is an increase in pulmonary capillary pressure associated with passage of a normal to high cardiac output in a reduced volume pulmonary vascular bed. The second factor, as demonstrated by protein content in the edema fluid, is injury to the alveolar capillary membrane. PMID- 2225970 TI - Diagnosis of tracheal injury in mechanically ventilated premature infants by flexible bronchoscopy. A pilot study. AB - Flexible bronchoscopy (FB) is uniquely suited for the study of large airway lesions in the ventilated premature infant. However, no standardized clinical scoring system of distal tracheal injury exists and the adverse consequences of FB in ventilated premature infants are not well described. Using a prototype Olympus fiberoptic ultrathin bronchoscope with a directable tip and an outer diameter of 2.2 mm, we serially scored distal tracheal injury in conventionally ventilated premature infants on the basis of mucosal and obstructive changes observed at bronchoscopy. In addition, we prospectively evaluated the incidence of adverse cardiovascular and pulmonary effects during, immediately after, and within 1 h of FB. We performed 21 FBs in eight conventionally ventilated premature infants with birth weight of 1,239 +/- 438 g and gestational age of 30 +/- 3 weeks. The carina and mainstem bronchi were easily visualized in all infants using the prototype bronchoscope. During the first several days of life, moderate-to-severe distal tracheal mucosal injury occurred frequently, while moderate-to-severe obstructive injury occurred infrequently. Distal mucosal injury appeared to improve during the fourth week of life. Mild distal obstructive injury began to appear during the second week of life. Adverse consequences of FB observed in our patient population included transient hypoxemia and bradycardia during FB, changes in systolic blood pressure immediately and within 1 h after FB, and emesis immediately after FB. Serious adverse cardiovascular or pulmonary effects were not observed. We conclude that FB can be performed safely with appropriate monitoring and is a useful tool in the clinical assessment and serial evaluation of distal tracheal injury in ventilated premature infants. We speculate that moderate-to-severe distal tracheal mucosal injury may be associated with the development of later obstructive injury. On the basis of this preliminary study, further prospective investigations of tracheal injury in ventilated premature infants appear to be warranted. PMID- 2225971 TI - Pulmonary complications of leukemia. PMID- 2225972 TI - Measuring crackles. AB - Crackles heard on auscultation can be represented graphically as a time-amplitude plot of the associated waveform. To assess the relative merits of several measures which might be considered for machine implementation in diagnostic instruments, we compared the reproducibility of those based on the initial voltage deflection which begins a crackle with those based on the largest deflection. The latter group showed less interobserver and less intraobserver variability when the same crackles were measured twice by each of two observers. Crackles from a teaching tape, categorized as fine and coarse, were used in this study. The ability of the various measures tested to distinguish between fine and coarse crackles on an individual basis was assessed and found to favor the measures based on the largest deflection. They showed an average of 9.96 percent incorrectly classified crackles, as opposed to 19.53 percent for the two measures based on the initial deflection. PMID- 2225973 TI - Pulse oximetry. Uses and abuses. AB - Pulse oximetry has made a significant contribution to noninvasive monitoring in a wide variety of clinical situations. It allows for continuous reliable measurements of oxygen saturation while avoiding the discomfort and risks of arterial puncture. As the extent of hypoxic episodes during various procedures and clinical settings is better appreciated, the role of continuous noninvasive monitoring will undoubtedly expand. An understanding of the principles and technology of pulse oximetry will allow physicians to obtain maximal clinical benefit from its use. PMID- 2225974 TI - Diagnostic thoracentesis. PMID- 2225975 TI - Gravity-dependent infiltrates in a patient with lipoid pneumonia. PMID- 2225976 TI - Anti-Kveim monoclonal antibody. New monoclonal antibody reacting to epithelioid cells in sarcoid granulomas. AB - A monoclonal antibody to the sarcoid granulomagenic agent contained in Kveim suspension was prepared by immunizing mice with Kveim suspension. One monoclonal antibody (IHY-1) that reacted with the epithelioid cells in sarcoid granulomas on immunoperoxidase technique was selected. The immunoperoxidase technique was used to compare this monoclonal antibody's binding to sarcoidosis- or tuberculosis affected lymph nodes. IHY-1 is a monoclonal antibody of IgM class. This antibody did not react to erythrocytes, lymphocytes, monocytes, alveolar macrophages, or the macrophage-derived cell lines such as U-973 and KG-1. It reacted to granuloma epithelioid cells of sarcoidosis-affected lymph nodes. The monoclonal antibody also reacted positively to epithelioid cells in tuberculous granulomas although the reaction was not as strong. Since IHY-1 was found to bind to both types of granulomas, this suggests that the epithelioid cells in sarcoidosis have antigenicity common to the epithelioid cells in tuberculosis. PMID- 2225977 TI - Thermodilution right ventricular ejection fraction. Catheter positioning effects. AB - Right ventricular (RV) ejection fractions have been difficult to estimate clinically. It has been demonstrated recently that RV ejection fractions can be calculated by thermodilution techniques using a rapid response thermistor and computer. This method critically depends on adequate mixing of the thermal bolus and sensing of the rapid response thermistor. This study examined the effects of the thermistor position within the pulmonary artery and injectate site within the right atrium on RV thermodilution ejection fraction measurements. Ten pigs were instrumented with a RV thermodilution catheter in the pulmonary artery, an injectate catheter in the right atrium, an atrial-pacing electrode, and a systemic arterial catheter. The RV ejection fractions were determined using thermodilution in two ways: (1) with incremental increases in pulmonic valve to thermistor distance, and (2) with incremental increases in injectate port to tricuspid valve. These measurements were obtained at a paced rate of 107 +/- 1 beats per minute (bpm) and then repeated with pacing-induced tachycardia (140 bpm). The highest RV ejection fraction with the lowest coefficient of variation was with the thermistor 2 cm from the pulmonic valve (50 +/- 2 percent), with a significant decline from this value at 10 cm (42 +/- 4 percent, p less than 0.05). This reduction in RV ejection fraction values with increased pulmonic valve to thermistor distance became more pronounced with tachycardia where a significant decline in RV ejection fraction occurred at 4 cm from the valve when compared with 0 cm (38 +/- 6 percent vs 47 +/- 3 percent, respectively, p less than 0.05). There was no significant change in RV ejection fraction at any injectate port to tricuspid valve distance at the lower heart rate. With tachycardia, however, a significant decline in RV ejection fraction occurred with the injectate port located 7 cm from the tricuspid valve (p less than 0.05). These results demonstrate that RV ejection fractions can be reliably obtained using thermodilution. Positioning of the thermodilution catheter is an important consideration for obtaining optimal RV ejection fraction measurements. Care should be taken to position the catheter with the thermistor a minimal distance from the pulmonic valve and the injectate port within the central body of the right atrium. PMID- 2225978 TI - Rapid percutaneous tracheostomy. AB - We describe a new method of performing percutaneous tracheostomy rapidly and safely using a specialized instrument kit. The technique permits the safe insertion of a full-sized 7.0 (ID) or 7.5 mm (ID) cuffed cannula into the trachea within 1-2 min, through the membranous second intercartilagenous space. Animal studies have demonstrated a superior healing process compared to that seen after conventional tracheostomy techniques. PMID- 2225979 TI - Pseudoinfarction pattern on electrocardiogram after coronary artery bypass. PMID- 2225980 TI - Hemoptysis in a 49-year-old man. An unusual presentation of a sporadic disease. AB - Although amebiasis is prevalent in tropical and subtropical areas, it occurs sporadically in the United States. Pleuropulmonary involvement is seen in about 20 percent of the patients with amebic liver abscesses. We describe a patient with pleuropulmonary amebiasis who complained of hemoptysis but had no gastrointestinal symptoms. This rather unusual presentation caused a considerable delay in securing the diagnosis. PMID- 2225981 TI - Mechanism of intermittent preexcitation in the Wolff-Parkinson-White syndrome. The concept of electronically mediated conduction across an inexcitable gap. AB - A man with intermittent preexcitation in the Wolff-Parkinson-White syndrome is reported. Once a sinus impulse was blocked in the accessory pathway, the block (ie, loss of preexcitation) was continued for a while until a PP interval reached or exceeded a critical period inducing sudden reappearance of preexcitation. This critical period was considerably longer than the effective refractory period of the accessory pathway. These findings are explained by the use of the concept of electronically mediated conduction across an inexcitable gap in the accessory pathway. It seems that when loss of protection was maintained, the sinus impulse was blocked at the site proximal to the gap, but the impulse passing through the atrioventricular node always reached retrogradely the site distal to the gap, and therefore, the next sinus impulse was blocked again. PMID- 2225982 TI - Axillosubclavian vein thrombosis produced by retrosternal thyroid. AB - Several causes of axillosubclavian vein thrombosis have been described. Trauma to the subclavian vein by pacemaker wires or central venous lines as well as the so called effort thrombosis have been recognized as frequently diagnosed precipitating factors. A patient is herein presented with thrombosis of the subclavian vein caused by a giant substernal thyroid compressing the innominate vein. PMID- 2225983 TI - Rounded atelectasis complicated by obstructive pneumonia and pulmonary arterial thrombosis. AB - A patient with a history of asbestos exposure developed rounded atelectasis. The mass was associated with local bronchial obstruction, obstructive pneumonia and arterial thrombosis. Autopsy demonstrated marked pleural thickening and radiographically inapparent asbestosis. This is the first reported case in which seemingly benign rounded atelectasis not only increased morbidity, but also contributed to mortality through airway obstruction and local arterial thrombosis. PMID- 2225984 TI - Dialysis-induced respiratory acidosis. AB - The inability to increase alveolar ventilation can lead to CO2 retention and acute respiratory acidosis in patients with ventilatory limitation. In this case, a young woman receiving maximum ventilatory support was unable to excrete excess CO2, associated with increasing dianeal concentrations of peritoneal dialysis. Since the patient's lung disease had necessitated a large amount of ventilatory support, the patient was unable to increase VE appropriately to handle excess CO2. Peritoneal dialysate was an additional source of carbohydrates. Peritoneal dialysate is an additional carbohydrate source that may result in hypercapnia and respiratory acidosis in patients with respiratory compromise. To our knowledge, this is the first case report in an adult which demonstrates that peritoneal dialysis with high glucose loads produced an acute respiratory acidosis that was reversed by decreasing the glucose concentrations in the dialysate. Excess CO2 production should be considered with respiratory disorders associated with dialysis. PMID- 2225985 TI - Occult fatal pulmonary embolism with disseminated intravascular coagulation. An unusual case masquerading as miliary tuberculosis. AB - We report a fatal case of occult pulmonary embolism complicating bronchogenic carcinoma which presented with rapidly progressive pulmonary miliary shadows and respiratory failure. A clotting profile abnormality compatible with disseminated intravascular coagulation was noted. Postmortem examination showed extensive clots occluding the major pulmonary vessels and areas of pulmonary infarcts. Histologic examination revealed fibrin deposition in the microvasculature compatible with DIC. Cases of pulmonary embolism with DIC have previously been reported, but this is the first case with pathologic confirmation. Thus, unusual presentation with diffuse lung shadow and DIC should not deter the clinician from correct diagnosis so that appropriate treatment can be promptly started. PMID- 2225986 TI - Labetalol and MRI as initial medical and diagnostic modalities in a marfanoid patient with expanding ascending aortic aneurysm. AB - Marfan syndrome is a hereditable disorder of connective tissue that causes several distinct cardiovascular abnormalities, including aortic regurgitation, dissection, and aneurysm. These cardiac manifestations can be identified with echocardiography, computer tomography, and angiography. Standard treatment of an acute hypertensive crisis in Marfan syndrome uses propranolol and sodium nitroprusside. This patient with Marfan syndrome whose case is reported herein presented with chest pain, hypertensive crisis, and aortic insufficiency; labetalol was used successfully to treat the acute hypertensive crisis and magnetic resonance imaging (MRI) was used to differentiate between aortic dissection and an expanding aortic aneurysm. This report is unique in that labetalol was used to control the hypertensive crisis in Marfan syndrome and MRI was used as the initial diagnostic modality in an emergency setting. PMID- 2225987 TI - Pulmonary malignant angioendotheliomatosis. Presentation with fever and syndrome of inappropriate antidiuretic hormone. AB - A 64-year-old man presented with protracted fever, hyponatremia, and mononeuritis multiplex. Inappropriate antidiuretic hormone secretion was established. The absence of pulmonary infiltrates precluded any lung biopsy. Autopsy revealed malignant angioendotheliomatosis involving multiple organs including the alveolar septa and pulmonary vasculature. An early diagnosis of MAE in the setting of fever and SIADH may be possible via transbronchial biopsy. PMID- 2225988 TI - Electrocardiographic J waves after resuscitation from cardiac arrest. AB - A patient was monitored prior to, during, and after cardiac arrest with a Holter monitor and an electrocardiograph. The arrest occurred without any premonitory signs on the ECG. At the onset of the arrest, torsades de pointes ventricular tachycardia occurred, which quickly degenerated into ventricular fibrillation. After a successful second defibrillation, the patient developed Osborn waves, which subsided within a few minutes. PMID- 2225989 TI - Utility of angiograms in patients with catamenial hemoptysis. AB - Pulmonary endometriosis is the likely cause in patients with hemoptysis during menses. While we describe two cases of catamenial hemoptysis, which were localized with chest CT scanning, angiograms revealed normal appearance. We suggest that angiograms may have little value in the evaluation of patients with pulmonary endometriosis. PMID- 2225990 TI - Kyphoscoliosis and respiratory failure. A patient treated with assisted ventilation for 27 years. AB - A 62-year-old woman had had kyphoscoliosis since age 12 years. Respiratory failure developed at age 35 years following a respiratory infection. A tracheostomy was done and she required assisted ventilation using a respiratory (Bird). Many attempts at weaning her from the ventilator were unsuccessful. She has remained dependent on assisted ventilation for more than 27 years but has had a relatively comfortable and meaningful life. In 1983, a left pleuroscopy was done related to recurrent pneumothorax and numerous small bullae were seen on the lung surface. Recent investigation using computed tomographic scanning has shown patchy areas of emphysema in both lungs. Emphysema is not a feature of kyphoscoliosis and it is suggested that intermittent positive pressure applied to the lung over long duration may cause the lung destruction of emphysema. PMID- 2225991 TI - Use of Nd:YAG laser in endobronchial Kaposi's sarcoma. AB - An unusual case of endobronchial Kaposi's sarcoma causing right middle and lower lobe atelectasis is reported. The lesion was successfully removed with Nd-YAG laser photoresection. PMID- 2225992 TI - The malignancy-sarcoidosis syndrome. AB - In a retrospective review of six patients with malignancy preceding sarcoidosis, we found four cases of malignant lymphoproliferative disease (LD) and one case each of ovarian cancer and breast cancer. The median interval from onset or relapse of malignancy to sarcoidosis was nine months. Of the four patients with LD, sarcoidosis appeared within six months of termination of chemotherapy for three of the patients and 15 months after allogeneic bone marrow transplantation for the fourth patient. At the time of diagnosis of sarcoidosis, there was no clinical or pathologic evidence of malignancy in the chest. We conclude that in contradistinction to the previously described syndrome of sarcoidosis preceding LD, there exists a syndrome of sarcoidosis following malignancy with or without chemotherapy. PMID- 2225993 TI - Septic pulmonary emboli. A rare cause of bilateral pneumothorax in drug abusers. AB - An intravenous drug abuser presented with bilateral pneumothorax. This is a previously unreported (to our knowledge) complication of septic pulmonary emboli secondary to right-sided endocarditis. This possibility must be considered in the differential diagnosis of pneumothorax in drug addicts. PMID- 2225994 TI - A case of massive true thymic hyperplasia with non-Hodgkin's lymphoma. AB - A case of massive true thymic hyperplasia with non-Hodgkin's lymphoma of the mediastinum is reported in a 14-year-old boy. Computed tomographic scan of the chest showed a mass of the anterior mediastinum and conspicuous swelling of the lymph nodes in the upper and lower mediastinum. They were grossly resected. The tumor of the anterior mediastinum was histologically diagnosed as true thymic hyperplasia. All of the mediastinal lymph nodes were diagnosed as non-Hodgkin's lymphoma, diffuse, mixed small and large cell type. PMID- 2225995 TI - Confirmation of endotracheal tube positioning. PMID- 2225996 TI - Allergies and asthma. PMID- 2225997 TI - Sources of endobronchial metastases. PMID- 2225998 TI - Advertising and clinical investigation. PMID- 2225999 TI - Choosing tidal volume for ventilation. PMID- 2226000 TI - Cardiac fossa. PMID- 2226002 TI - Occupational asthma. PMID- 2226001 TI - Environmental and occupational asthma. PMID- 2226003 TI - Role of the physician in environmental and occupational asthma. PMID- 2226004 TI - Epidemiology and surveillance. PMID- 2226005 TI - Surveillance of occupational asthma under the SENSOR model. PMID- 2226006 TI - Asthma surveillance in the United States. A review of current trends and knowledge gaps. PMID- 2226007 TI - Epidemiologic studies of asthma epidemics in Barcelona. PMID- 2226008 TI - Asthma and persistent wheeze in the Harvard Six Cities Study. PMID- 2226009 TI - Clinical surveillance and management of occupational asthma. Tertiary prevention by the primary practitioner. PMID- 2226010 TI - Clinical assessment of bronchial hyperresponsiveness due to nonspecific and specific agents. PMID- 2226011 TI - Use of immunologic technology in the diagnosis of environmental and occupational immunologic lung disease. PMID- 2226012 TI - Environmental and occupational asthma. Exposure assessment. PMID- 2226013 TI - Evaluation of a proposed NIOSH surveillance. Case definition for occupational asthma. PMID- 2226014 TI - Clinical management when the environment can be changed. PMID- 2226015 TI - A framework for assessing impairment from asthma. PMID- 2226016 TI - Assessing disability from occupational asthma. A perspective on the AMA guides. PMID- 2226017 TI - Environmental and occupational asthma. Reports of the Working Groups. PMID- 2226018 TI - [Use of conscious sedation by inhalation in dental practice and oral surgery]. PMID- 2226019 TI - ["Master surgeons" and "privileged surgeons"]. PMID- 2226020 TI - [Essentials of the biochemical profile]. PMID- 2226022 TI - [Giving meaning to work. Comments on the occupational structure of medical careers]. PMID- 2226021 TI - [Use of Kevlar fibers in semi-permanent periodontal splinting]. PMID- 2226023 TI - [The physician must present newspaper articles, of possible advertising value for his services, for approval before their publication]. PMID- 2226024 TI - [Diagnosis and prognostic assessment of bronchial cancer]. PMID- 2226025 TI - [Surgical therapy of bronchial carcinoma]. PMID- 2226026 TI - [Long-term results after surgical treatment of lung metastases]. PMID- 2226027 TI - [Surgical therapy of lung complications of long-term ventilation for severe adult respiratory distress syndrome]. AB - Long-term respiratory therapy with high pressure levels in case of ARDS can lead to several symptoms requiring surgical treatment. Various forms of manifesting barotrauma predominate (bronchopleural fistula, pneumothorax, pneumatocele and soft tissue emphysema), while hematothorax, infected necrosis of parenchyma or esophagotracheal fistula are rare. Most of the operations became necessary because of bronchopleural fistula resp. pneumothorax, and with this indication the number of reoperations was especially high. Of 21 patients 13 (62%) survived. PMID- 2226028 TI - [Preoperative assessment of perirectal lymph nodes by ultrasound]. AB - Endorectal ultrasound is a new technique which is having an increasing impact on the surgical community. Beyond the assessment of tumor penetration depth two kinds of lymph nodes are to be differentiated by ultrasound in the perirectal fat. 1) Inflammatory enlarged lymph nodes which appear hyperechoic, unsharply limited to the surrounding tissue and 2) lymph node metastases which are hypoechoic having the same density as the tumor. Sensitivity and specificity of endorectal ultrasound in the detection of lymph node metastases in 97 patients was 80%, the positive predictive value was 78%, the negative 82%. In an in vitro study we examined 27 lymph nodes of patients with either inflammatory or cancerous colon diseases by computerized B-scan texture analysis. An HP-77020 A realtime electronic sector-scanner was connected with HP-1000 microcomputer which permitted the selection and texture-analysis of a region of interest (ROI). Afterwards the lymph nodes were examined histologically. Independent of size and surrounding fat tissue there was a highly significant difference between inflammatory and cancerous enlarged lymph nodes concerning mean grey level and mean gradient. Tumor infiltrated lymph nodes are hypoechoic with poor contrast within the node whereas inflammatory enlarged nodes are more hyperechoic and show more contrast. Thus, we can state that it is possible by consideration of echogenity and contrast to distinguish sonographically between tumor infiltrated and inflammatory enlarged lymph nodes. PMID- 2226029 TI - [Is liver biopsy in gallbladder operations still indicated?]. AB - Biopsy of the liver with the Tru-cut needle was done as a routine diagnostic procedure during gallbladder surgery in 166 cases. The data of history, ultrasonography and laboratory were compared with the microscopic liver findings. Preoperatively in 89% of the cases there was an indication for liver biopsy. In 11% of the cases, where there was no indication for preoperative biopsy, we found severe changes in liver histology. Therefore we recommend liver biopsy during gallbladder surgery as a routine procedure. PMID- 2226030 TI - [Primary therapy of polytraumatized patients and reasons for early transfer to a specialty hospital]. AB - 200 polytraumatized patients were treated at our institution between 1.1.1987 to 28.2.1989. 58 patients had been submitted from other hospitals. Reasons for submissions were complex cranio-facial-trauma in 27 patients, thoracic trauma in 9 patients and complex abdominal injury in 8. In 13 of 44 patients (29.5%), submitted in between the first 24 h after trauma, severe and partially life threatening injuries had not been diagnosed at the first hospital. Failures in decision making burden especially patients with cranio-facial injuries, in whom intraabdominal and thoracical injuries are often overseen. Patients with abdominal trauma were often submitted after an operative attempt demonstrating complex traumatisation which was underestimated at primary diagnosis. Polytraumatized patients need to have a multidisciplinary management performed by a specified crew with all diagnostic facilities available to avoid overestimation or neglection of additive injuries. Direct submission into a specified medical center is therefore recommended and seems preferable to submission after failed or insufficient primary therapy in inadequately equipped smaller hospitals. PMID- 2226031 TI - [Managing bile duct defects by pedicled ligamentum teres hepatis]. PMID- 2226032 TI - [Invagination of the left colon in adults]. PMID- 2226033 TI - [First fully implantable intramedullary system for callus distraction- intramedullary nail with programmable drive for leg lengthening and segment displacement. Principles and initial clinical results]. PMID- 2226034 TI - [Comment on the contribution by D. Kistler et al.: Combined surgical-radiologic procedure in closure of a hemodialysis shunt]. PMID- 2226035 TI - [Spiroid fractures of the thoracic and lumbar spine]. AB - The review of our observations of fractures of the thoracic and lumbar spine (588 files could be used from 1969 to 1989) allowed us to demonstrate fractures not included in the usual classification. In our opinion, the fracture line is spiral. The mechanism therefore includes a very likely axial rotation. The fracture line may be confined to the vertebral body (this is the type called S1) or extends to the posterior arch as well (S2 type). The fractures often cause nerve root lesions. However, no complications involving the cord were noted in our series, even in the few cases showing considerable displacement. Note the tendency to axial telescoping of the focus, which requires specific modalities of treatment. PMID- 2226036 TI - [Do peroperative blood transfusions have a negative effect on the developmental prognosis of colorectal cancers]. PMID- 2226037 TI - [Experience in hepatic transplantation. Report of 118 cases]. AB - From February 1978 to November 1989, 118 orthotopic liver transplantations were performed in 106 patients, including 100 adults and 6 children; 11 of these grafts were performed before 1984. The study of this series emphasizes the casuistical peculiarities, with high incidence of alcoholic cirrhosis, 24/106 (22.6%) and of fulminating hepatitis, 17/106 (16%). The study of the results yields a real survival rate of 61% in the total series, 78% for the recent period including the past 3 years, and 86% if excluding the emergent cases. The comments also deal with the changes in the procedure and in postoperative complications, with some immunological issues and with the peculiar features connected with the insertion of this operation into a combined medical and surgical program of multi organ transplantation. PMID- 2226038 TI - [Crohn's disease of the small intestine]. AB - Any symptomatic manifestation of Crohn's disease results not from the disease itself but from some complication. The first complication is stenosis, which precedes and favors the appearance of abscesses, fistulae, perforations and sometimes hemorrhages. The ideal treatment consists in identifying and treating the disease as early as the appearance of stenosis and before the other complications occur. In our series, mortality most often was caused by an infection that was not or poorly managed, even when the primary cause of death was embolism or sometimes a massive hemorrhage. In many patients, the risks of septic complications are all the higher as the subject's immunological defense is weakened by immunodepressive corticosteroid treatments and by malnutrition. All septic foci must therefore be located and drained before any extensive surgical operation. Malnutrition can be improved by parenteral nutrition, and often by enteral feeding as well. After severe surgical complications, the next operation should not be performed until 12 weeks have elapsed, in order to reduce both technical difficulties and risks. PMID- 2226039 TI - [Pulmonary metastases of colorectal origin]. AB - From January 1979 to December 1988, 18 patients with pulmonary metastases from colorectal cancers were operated in our division. This series included 11 men and 7 women (average age 57 years). The primary cancer was colic in 6 cases and rectal in 12. In 3 cases, the metastases were synchronous and discovered during the initial assessment. In 15 cases, they were metachronous, without symptoms in 12 cases and symptomatic in 3. These metastases were single in 14 cases, multiple in 3, bilateral in 1. They were peripheral in 15 cases. The histological diagnosis was obtained preoperatively in 5 cases (27.7%). The procedures uses were lobectomy for 11 patients, segmentectomy for 1, wedge resection for 10. Postoperative chemotherapy was given to 7 patients. Benign complications occurred in 2 cases during the postoperative period. No perioperative death was noted. One patient was lost to follow-up without recurrence after 1 year, 6 patients died from neoplastic evolution 4, 8, 15, 17, 22 and 28 months after being operated. In May 1989, 11 patients were still living: -2 scheduled for the excision of a contralateral lesion, -2 with pulmonary recurrence. 7 patients were alive without recurrence 12, 14, 17, 46, 52, 68 and 108 months after being operated. The probability of occurrence of pulmonary metastases in the evolution of colorectal cancer is estimated between 20 and 50%. Only 1% of the patients can be treated surgically. When screening these lesions, one must bear in mind that their appearance is sometimes quite delayed, and often asymptomatic. The repeated use of tracers is necessary but not sufficient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226040 TI - [Lightning injuries in high mountain areas. Report of 29 cases]. AB - Lightning, usually scarce, is a frequent phenomenon in high mountains. Due to our location at the foot of the Mont-Blanc, we have been able to examine twenty nine cases of people struck by lightning in the Chamonix Hospital. Lightning that has interested people since old times is the result of complex meteorological phenomenons, able to deliver a huge instant power. Several types of lightning have been described. They give different sorts of injuries; the most frequent affect the brain, the heart and the skin. The analysis of the results of seventeen victims admitted at the hospital does not allow to conclude to a clinical and biological specificity of the lightning stricken in high mountains. It makes it however possible to determine precisely the clinical disorders and the features of the injured and to emphasize the part due to the high mountains and consider the non specific therapeutic to set to work as soon as possible. PMID- 2226042 TI - [Pericystic pathology and surgery of hepatic hydatidosis. Studies and personal experiences]. AB - In the general study of the consequences of hydatid cysts on the parenchyma of the organ involved, particular interest was given to the conditions of the pericyst. Thus a genuine pericystic pathology was systematized for most evolved pericysts. The signs vary according to the various conditions, sometimes including simple fibrosis, sometimes calcifications with specific and different appearances, almost always chronic inflammation. Fissuration was rare and, more importantly, exogenous vesiculation, a frequent cause of recurrence, was more often noted. The treatment is chosen on these bases, and determined by the local situation, hepatobiliary complications and the general condition of the patient. The author demonstrates the surgical evolution he followed in relation with the progress made in liver surgery, from plain drainage methods to radical pericystectomy and hepatic resection procedures. The conclusions he has drawn as a Symposium moderator during the World Congress of Hydatology held in Madrid in 1985, which will be summed up in the report, still seem to be perfectly valid. PMID- 2226041 TI - [Emergency surgery of complicated diverticular disease of the colon]. AB - Emergency surgery is aimed at achieving the same results as elective surgery, but still has specific limitations in the case of CDDC, in spite of significant progress. We describe the physiopathological bases of the emergent treatment of the septic, occlusive and hemorrhagic complications of the CDDC, as well as the experience acquired in the Emergency Unit and Department 3 Hospital San Jose with 54 cases operated since 1981. The modern means of intensive care and preparation, including powerful antibiotics, make primary resection (1) as a principle possible, but do not allow yielding to the temptation of immediately creating an anastomosis as long as the local conditions have not improved. On the other hand, we emphasize the advantages of performing primary resection-anastomosis surgery in elective operations for non-emergent cases. PMID- 2226043 TI - [Pharyngoesophageal reconstruction using a vascularized free jejunal graft. Indications--technique and surveillance. Report of 90 cases]. AB - Several procedures have been proposed for pharyngoesophageal reconstruction. The use of a revascularized free jejunal graft currently appears to be a method of choice for anatomical, physiological and technical reasons. The authors currently look back on a series of 90 patients having received a revascularized free jejunal graft between 1978 and 1989 inclusive. The indications predominantly include cancer of the pharynx invading the posterior wall and preserving the cervical esophagus, requiring total circular pharyngolaryngectomy (77 cases). Some benign lesions involve reoperated patients (13 cases). The technique for obtaining the jejunal graft is accurately codified: use of the 3rd jejunal loop in isoperistaltic conditions, refrigeration during the period of ischemia, revascularization by the cervical vessels. If a salvage operation is needed, it is necessary to prepare a saphenous venous graft at the beginning of the operation (3 cases). These grafts must be observed daily. Early negative signs include unexplained epistaxis, blood in the saliva, cervical skin suffering. Emergency fiberscopy must be performed with a bronchoscope or a rhinofiberscope. In case of suffering or necrosis of the graft, the patient must be reoperated immediately and a second free jejunal graft must be placed. The absence of postoperative mortality, low morbidity and good functional results obtained in the series are convincing reasons for using this procedure. PMID- 2226044 TI - [Cancer of the anus. Current role of surgery]. AB - 70 cases of carcinoma of the anus are described in a retrospective study. All patients had been operated, since surgical treatment was regarded as the method of choice at that time. Our work therefore consists in assessing the role of surgery in the treatment of such carcinomas. In the initial forms, extended sphincter saving exeresis allowed excellent results (100% survival over a 1- to 10-year follow-up). In more advanced lesions, treated with abdominoperineal resection, the survival rate was 50% after 5 years. The same figure was obtained in case of extension to the female genital organs (the invasion of which is not a pejorative sign), while the prognosis was considerably worsened for the patients who had had lymph node resection due to invasion of inguinal nodes (20% survived after 5 years). Local surgical exeresis currently is as valuable as radiation therapy, but the latter is clearly indicated for advanced carcinomas, for which mutilating surgery has not demonstrated its superiority. PMID- 2226045 TI - [Supraselective or proximal gastric vagotomy. Report of 1,250 surgical cases. 777 special cases with objective follow-up for over 10 years]. AB - From August, 1970 to February, 1989, we performed 1,105 elective and 145 emergency PGVs (proximal gastric vagotomy). The emergent cases included 118 perforations and 27 bleeding lesions. Since September, 1973, we have been able to measure the pH of the mucosa using a GR282C transesophageal electrode. Two cases of exitus (0.2%) were noted. With an intraoperative test (pH) or the systematic section of the gastroepiploic nerve (n.ge) (randomized with 269 cases followed up over 57 months) the rate of recurrence does not exceed 2%. Without these "tools", it is as high as 10%. Since this rate is still a cause of confusion in this 20th year of PGV, we analyse 684 "stabilized" (excluding the first 10 patients of each surgeon). PGVs followed up (88% of 777 PGVs) over 10 to 17 years. The study was clinical and radiological in 100% of cases, based on acid secretion in 2/3, and fiberscopic in 47%. Between 5 and 17 years, 318 patients had a fiberscopic study and 325 an analysis of the basal and stimulated acid secretion (76% were already evaluated preoperatively). Two types of recurrence were defined: those due to failure of the surgeon or technique (gastroepiploic nerve in 1/5 of cases) involving acidity--this being the "persistent" ulcer (3/4 of cases during the first years); and disorders in gastric evacuation (?) with a very low acidity level, also causing more delayed gastric ulcers. The non-cumulative probability of R in successive years stays around 0.2 to 0.1% after the 3rd or 4th year following the PGV, and the total rate after 10 years or more is about 10%. If performed by experienced surgeons and with the intraoperative test (or systematic section of the n.ge), PGV should have only a low rate of failure, these cases being more amenable to treatment than an anastomotic mouth ulcer following resection, for instance. PMID- 2226046 TI - Ultradian rhythms in the EEG and task performance. AB - The purpose of this work was to investigate the presence of ultradian rhythms in: 1. levels of electroencephalographic activation; 2. interhemispheric correlation and 3. the performance of two cognitive tasks, and the correlation between these variables. Eight volunteers, aged 20 to 30, participated in the experiment. Two sessions were carried out: one from 0800 to 1400 on one day and the other from 1400 to 2000 another day. Samples of EEG activity were taken every 15 min at rest with eyes open in left and right temporal, central, parietal and occipital derivations referred to the ipsilateral earlobe the performance on two tasks, one logico-analytical (left hemisphere functions) and one spatial test (right hemisphere functions) was assessed. As control, body and environmental temperature were recorded. To test for the presence of ultradian rhythms, the data were subjected to a Fourier analysis. Different EEG variables showed rhythmicity throughout the sessions, principally with slow oscillation periods (3 and 6h); ultradian rhythms with 3h periods were also found in body temperature, while task performance showed no significant rhythmic patterns during sessions. Finally, no significant correlations were found between physiological variables evaluated and task performance. PMID- 2226047 TI - A chronobiological study on the relation between heart rate and QT interval duration in newborn infants. AB - The relation between heart rate and QT interval is the result of the autonomic nervous system control on cardiac function in healthy adults; accordingly, chronobiological studies have shown that adult subjects have circadian rhythms of heart rate (expressed as R-R interval) and QT interval in phase. We have employed chronobiological methods to study heart rate and QT interval relation in 10 newborn infants, who are known to have an immature cardiac control. Findings from this study indicate that not all the newborns show circadian rhythms of heart rate and QT interval and that when both rhythms are present they do not correlate like in the adults. Likely, this lack of relationship between heart rate and QT interval in newborns is due to different maturational stages of the newborns studied. As a practical implication, in newborn infants, mathematical correction of QT interval by heart rate is not a reliable method. PMID- 2226048 TI - Lunar phase influence on the glycemia of worker honeybees. AB - The variations of the concentrations of trehalose and glucose, the major components of the haemolymph of emerging worker honeybees, have been examined with respect to the lunar phase. Two series of experiments were performed independently, from April to June and from July to September respectively. The results revealed significant peakings for both carbohydrates at full moon and at new moon, and also a minor peak at last quarter. The data obtained for trehalose in the July-September period are consistent with the existence of a circaseptan subcomponent of period tau congruent to 132h. PMID- 2226049 TI - [Etiological and influential factors of involutional osteoporosis in old Chinese]. AB - A comprehensive analysis is reported in 376 healthy middle and old-age persons, including measurements of bone mineral content (BMC) of the mid-radias, pituitary sex hormones (RIA), serum calcium, phosphate, albumin, alkaline phosphatase, urinary calcium, phosphate, hydroxyproline (BCA), daily intake of protein and calcium, physical exercise and activity, body weight, amenorrhea etc. Results showed that the preponderance of bone resorption over bone formation is the essential pathophysiological change of involutional osteoporosis. For females, bone loss is regulated mainly by estrogen in presenile group, co-regulated by estrogen and androgen in senile group. For males, urinary hydroxyproline excretion is also regulated by estrogen A remarkable correlation was observed between BMC and the following factors: serum calcium, urinary calcium, hydroxyproline, body weight, physical exercise, amenorrhea, intake of protein and calcium. Our data indicated that the intake of calcium daily in old chinese should not be lower than 700 mg (male) and 900 mg (female), protein should not be lower than 60-70 g. The age of onset, prevalence rate and BMC average reduction rate of osteoporosis in chinese were also observed in the studies. PMID- 2226050 TI - [Factors affecting parameters of left ventricular diastolic function derived from Doppler echocardiography]. AB - According to the data from left ventricular catheterization as well as M-mode and two-dimensional echocardiography in 36 patients, the influence of left ventricular diameter, systolic function, systolic and diastolic filling pressures on the parameters of left ventricular diastolic function derived from Doppler echocardiography was analysed. The results indicate: (1) the left ventricular end diastolic pressure, rapid filling wave pressure and the ratio of the both significantly affect the Doppler diastolic function parameters; (2) the decrease of the ratio of early-to-late diastolic mitral flow velocities (E/A) is only a manifestation of early stage of left ventricular diastolic dysfunction and the E/A ratio returns to normal (false improving) at advanced stage of left ventricular diastolic dysfunction. PMID- 2226051 TI - [Sulfur dioxide-induced bronchial constriction in asthmatics and its prophylaxis by salbutamol]. AB - Patients with bronchial asthma often develop acute attack in kitchen while burning honeycomb briquet which is widely used for cooking in southern China. Burning of a honeycomb briquet produces 0.6-4.3 ppm sulphur dioxide (SO2) in the kitchen air. To assess whether the above concentration of SO2 can induce bronchial constriction, we performed SO2 bronchial provocation test on 21 asthmatics (male 11, female 10, average age 28.8 +/- 2.0 years), 10 patients with allergic rhinitis (male 3, female 7.28 +/- 1.6 years) and 20 healthy non-smokers (male 13, female 7, 28.1 +/- 1.5 years). FEV1 showed no significant change in both healthy and rhinitis group even a maximal amount of SO2 (10 ppm) was given. The calculated PC20 FEV1 and PC35 SGaW in asthmatics were 3.7 +/- 0.22 ppm and 2.5 +/- 0.18 ppm respectively, which fell into the SO2 range yielded by a burning honeycomb briquet. Orally administered slow release salbutamol created protective effect in 5 out of 8 patients. Salbutamol inhalation, however, completely blocked SO2 induced bronchial constriction. We suggest that patient with bronchial asthma should receive salbutamol aerosol inhalation before cooking with burning honeycomb briquet. PMID- 2226053 TI - [Endogenous creatinine clearance rate and normal values in healthy young subjects]. AB - Serum creatinine (Scr) and creatinine clearance rate (Ccr) were measured for their normal values in young and youngster. The subjects included 251 health individuals between the age of 15 and 29.251 of them were tested actually. The datum had been treated by a computer. The Scr normal values are 72.49 and 50.39 mumol/L respectively in the males and females. Their means showed significance differences between the males and females. The upper limit of 95% of normal values were 94.59 and 66.3 mumol/L respectively. The Ccr means of the males and females were 136.89 and 132.13 ml/min/1.73 m2 respectively. Their means showed no significance difference between them. A common lower limit of 95% of normal values was 75.03 ml/min/1.73 m2. It is expected that the information above provide a scientific base and important reference in the future. PMID- 2226052 TI - [Detection and clinical significance of anti-histone antibody in systemic lupus erythematosus and rheumatoid arthritis]. AB - Determinations of anti-histone antibodies (AHA) by ELISA were carried out in 109 cases of SLE, 117 of RA, the positive rate being 50.5%, 23.1% respectively, with titres in SLE patients higher than in RA. AHA was 90.2% positive in active cases of SLE patients. SLE patients with AHA showed a higher incidence of pericarditis and arthritis, but a lower rate of malar rash than SLE patients without AHA. In RA, there is a higher incidence of extraarticular manifestations in AHA positive patients IgM-AHA was this predominant AHA in RA while in SLE patients it was the IgG-AHA. For SLE, IgG-AHA which was more closely associated with anti-ds DNA was more significant than IgM-AHA. PMID- 2226054 TI - [Androgen treatment of hematologic diseases]. PMID- 2226056 TI - Functional assessment of the anorectum in faecal incontinence. AB - The functional ability of the anorectum to maintain continence is best assessed by a provocative assessment of continence to a standard load of rectally infused saline. Faecal incontinence is not caused by one condition. The combination of multiport anorectal manometry, electrophysiology and rectal sensory testing can identify several causes, which logically require different treatments. Only time and carefully conducted trials will establish whether such functional testing will be useful. PMID- 2226055 TI - Neurobiology of incontinence. A symposium. London, 11-13 October 1989. Proceedings. PMID- 2226057 TI - Functional assessment of the bladder. AB - The urinary bladder has two functions: to store and to empty. A frequency-volume chart completed by the patient provides useful information about voiding intervals, possible factors provocative for incontinence, functional bladder capacity and daily urine volume. Filling cystometry is used primarily to evaluate reflex function in the storage phase, giving information about the presence or absence of detrusor instability and (in combination with urethral EMG) about detrusor-sphincter coordination. Information is also obtained about bladder sensation, bladder capacity and bladder compliance. Detrusor function during emptying is closely related to outflow conditions and therefore demands simultaneous registration of detrusor pressure and urinary flow rate. An inverse relation exists between detrusor pressure and flow rate, which means that reduced flow rate causes increased detrusor pressure for the same detrusor power. Underactive detrusor function will result in low detrusor pressure and low flow rate. The finding of a non-contractile detrusor may indicate psychogenic inhibition or a neurogenic lesion. Sacral evoked potentials and denervation supersensitivity tests may help to distinguish between these conditions. PMID- 2226058 TI - The neurogenic hypothesis of stress incontinence. AB - There are a number of causes of incontinence. The common forms of urinary incontinence, faecal incontinence or double incontinence, are stress related, in that voiding of urine or faeces occurs in response to a sudden increase in pressure in the bladder or anorectum that is not opposed by an adequate pressure increase in the sphincteric region. This weakness of the sphincter mechanism is due to chronic partial denervation of the striated sphincter muscles of the pelvic floor, comprising the external and sphincter muscle and puborectalis (puboanalis) components of the voluntary anal sphincter musculature, and the periurethral and intramural components of the urinary striated sphincter musculature. Denervation of these muscles occurs progressively following injury initiated during childbirth and then sustained by repeated stretch-induced injury during straining behaviour at stool. Age-related changes to this innervation may also be important. Weakness of the pelvic floor, and perineal descent during straining, lead to secondary changes in the anatomy of the bladder neck, of the anorectal angle, and of the smooth muscle of the internal urinary and anal sphincters. The cystometric and anal manometric changes found in patients with stress incontinence are secondary to this neurogenic weakness of the pelvic floor. PMID- 2226059 TI - Stress urinary incontinence. AB - Stress urinary incontinence due to urethral sphincter incompetence (genuine stress incontinence) afflicts some 5-15% of women. The mechanism of continence is imperfectly understood, as is the precise mode of its cure, whether conservative or surgical. The pathophysiology is a reduction in urethral resistance in the absence of detrusor activity. Aetiological factors include congenital malformation of the bladder neck, denervation of the pelvic floor and sphincter mechanism following childbirth, trauma causing disruption of the urethral sphincter mechanism, fibrosis associated with bladder neck surgery for prolapse, oestrogen deprivation at the menopause, and urethral relaxation or instability. Conventional investigations include urethral pressure measurement, urethral electric conductance, electrophysiological tests, and cystometry or videocystourethrography (the latter procedures diagnose by exclusion). A more precise evaluation of the role of urethral resistance is hampered by lack of suitable techniques for measuring urethral and sphincteric function. Treatments include pelvic floor exercise, drugs to increase urethral resistance, and surgery, either to evaluate the bladder neck or to increase urethral resistance. PMID- 2226060 TI - Detrusor-external sphincter dyssynergia. AB - Detrusor-external sphincter dyssynergia (DESD) is characterized by involuntary contractions of the external urethral sphincter during an involuntary detrusor contraction. It is caused by neurological lesions between the brainstem (pontine micturition centre) and the sacral spinal cord (sacral micturition centre). These include traumatic spinal cord injury, multiple sclerosis, myelodysplasia and other forms of transverse myelitis. There are three main types of DESD. In Type 1 there is a concomitant increase in both detrusor pressure and sphincter EMG activity. At the peak of the detrusor contraction the sphincter suddenly relaxes and unobstructed voiding occurs. Type 2 DESD is characterized by sporadic contractions of the external urethral sphincter throughout the detrusor contraction. In Type 3 DESD there is a crescendo-decrescendo pattern of sphincter contraction which results in urethral obstruction throughout the entire detrusor contraction. In patients with sufficient manual dexterity the most reasonable treatment option is to abolish the involuntary detrusor contractions (to ensure continence) and then to institute intermittent self-catheterization (in order to empty the bladder). The bladder may be paralysed pharmacologically or may be surgically converted to a low pressure urinary reservoir by the technique of augmentation enterocystoplasty. In quadriplegic men, transurethral external sphincterotomy may be performed and the incontinence managed with an external urinary appliance. Without proper treatment over 50% of men with DESD develop serious urological complications within about five years. In women these complications are much less common. PMID- 2226061 TI - The physiological evaluation of operative repair for incontinence and prolapse. AB - Women with incontinence were divided into 30 with anorectal incontinence and 63 with complete rectal prolapse. The former group comprised 14 with a sphincter disruption and the remainder with intact sphincters. After anterior sphincter repair 70% were restored to acceptable continence. Success was associated with a rise in resting and voluntary contraction pressures and improved anal sensation. Patients with prolapse underwent either anterior and posterior rectopexy, or resection rectopexy. Continence was improved in both groups. Postoperatively, 90% following resection rectopexy and 80% following anterior and posterior rectopexy were restored to acceptable continence. Postoperative defaecatory straining and incomplete evacuation were reduced, with no significant differences between the two procedures. Restoration of continence was not associated with any change in sphincter pressures. However, rectal sensory threshold and anal sensation were both improved. PMID- 2226062 TI - Surgical approaches to anal incontinence. AB - Primary repair of acute anal sphincter injuries by direct apposition of the severed external sphincter without tension is advisable whenever feasible. However, the majority of patients who are candidates for surgical treatment of anal incontinence will undergo a secondary repair, the type of which will depend on the underlying aetiology and the surgeon's preference and experience. The most successful of these procedures is sphincter reconstruction with or without levatoroplasty for a disrupted anal sphincter (due to surgical, obstetrical or other trauma) in the absence of underlying neurological damage. Success rates are reported at 80-90%. Post-anal repair is advocated for patients with a poorly functioning sphincter with an obtuse anorectal angle, most of whom have a neurogenic basis for their incontinence. Success rates vary from 60 to 75% of cases but long-term results have been less satisfactory. Rectal procidentia is associated with faecal incontinence in 65-75% of cases. Abdominal repair (we favour suture rectopexy with sigmoid resection) restores continence in 50-80% of such patients. Patients with persisting incontinence are candidates for post-anal repair. Anal encirclement with an elastic, Dacron-impregnated Silastic sleeve has a limited role in selected patients. For more severe incontinence, muscle transfers (gracilis, gluteus maximus, etc.) can achieve some success but continence is less than perfect. We are currently assessing the use of an artificial anal sphincter (a modification of the AMS 800 urinary sphincter). For patients who fail all therapeutic options, a stoma will provide a better lifestyle than coping with the consequences of faecal incontinence. PMID- 2226063 TI - Treatment of urinary and faecal incontinence by surgically implanted devices. AB - Three kinds of implant to treat incontinence are considered. The sacral anterior root stimulator (with sacral posterior rhizotomy) is already effective in urinary incontinence due to spinal cord injury, and will have wider application. The conditional pudendal nerve stimulator and the conditional gracilis nerve stimulator are, respectively, almost untried and entirely untried devices; but they show promise, and if successful may help very many patients. PMID- 2226064 TI - Central neural control of the lower urinary tract. AB - The lower urinary tract has two main functions, the storage and periodic elimination of urine, which are regulated by a complex neural control system in the brain and spinal cord. This neural system exhibits switch-like patterns of activity that are generated by visceral reflex circuits, some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination centre (the pontine micturition centre) located in the rostral brainstem. This reflex pathway is, in turn, modulated by higher centres in the cerebral cortex which are presumably involved in the voluntary control of micturition. Several neurotransmitters (including GABA, opioid peptides and glutamic acid) appear to have a role in the central pathways controlling micturition. Since pharmacological manipulation of putative inhibitory transmitter mechanisms increases bladder activity and decreases bladder capacity it is possible that similar changes induced by pathological conditions may underlie bladder dysfunctions occurring in patients with neurogenic urinary incontinence. Further study of these neurotransmitter systems may yield new therapeutic approaches for the treatment of hyperactive bladder disorders. PMID- 2226065 TI - Urinary incontinence: classification and pharmacological therapy. AB - Pharmacological therapy has been developed which can have significant impact in the management of many forms of urinary incontinence and voiding dysfunction. In general the clinical laboratory studies which have supported or challenged the efficacy of many of the commonly prescribed drugs for voiding dysfunction are often difficult to interpret and contradictory. The available clinical studies often do not demonstrate a lack of bias. Nor do they include an adequate number of subjects, use appropriate and sensitive methods of evaluation, employ double blind placebo-controlled design, or appear statistically valid. Although the contribution of laboratory research has been of unquestionable value in the development of our current knowledge of lower urinary tract pharmacology it is difficult to interpret the results of in vitro pharmacological studies because of the array of experimental models used and the need to extrapolate to in vivo activity. This paper utilizes a functional scheme which classifies agents by their effects on urinary storage and emptying. The purpose of this review is to promote discussion of the application of uropharmacological investigation to the development of newer, more efficacious forms of drug therapy. PMID- 2226066 TI - Functional anatomy of the female lower urinary tract and pelvic floor. AB - Stress continence depends upon three factors: proximal urethral support, vesical neck closure, and urethral contractility. The position of the vesical neck is not static but mobile and under voluntary control. Its support depends upon connections of the urethrovaginal endopelvic fascia to the medial aspect of the levator ani. In addition, these fasciae are attached to the arcus tendineus fasciae pelvis which supports the urethra during levator relaxation, and probably during stress. Levator contraction supports the proximal urethra and also pulls the vesical neck anteriorly against a band of endopelvic fascia which is suspended between the arcus tendinei, compressing it closed. Relaxation of the muscles allows the vesical neck to descend, and facilitates its opening. The connective tissue and smooth muscle of the trigonal ring encircles the vesical neck's lumen, and may contribute to closure of this area. The striated urogenital sphincter muscle can contract to assist in maintaining continence in continent women whose vesical neck is not competent. It has a circular sphincteric portion from 20 to 60% of urethral length. From 60 to 80% it has a considerable bulk of muscle which forms an arch at the perineal membrane that would compress the urethra from above. PMID- 2226067 TI - The dual function of capsaicin-sensitive sensory nerves in the bladder and urethra. AB - The sensory innervation of the urinary bladder and urethra plays a key role in a variety of reflexes involved in urine storage and voiding. Dysfunction of these systems is a possible cause of many disturbances related to urine continence but basic knowledge in this field has been hampered by the lack of tools for studying sensory nerves. The use of capsaicin, the pungent ingredient of red peppers, allowed us to investigate the anatomical and functional properties of a specific subset of sensory neurons in the lower urinary tract. These 'capsaicin-sensitive' neurons play a dual sensory and 'efferent' function, determined by transmitter release from their central and peripheral nerve endings. Tachykinins, including substance P, and other neuropeptides such as calcitonin gene-related peptide, mediate the functions of these sensory neurons. The 'sensory' function includes regulation of micturition threshold, activation of cardiovascular reflexes and perception of pain from the urinary bladder. The 'efferent' function includes local regulation of muscle cell activity, nerve excitability, blood flow and plasma protein extravasation. Recent data suggest that capsaicin-sensitive sensory nerves could be present in the human bladder. PMID- 2226068 TI - Introduction, spread and subsequent disappearance of the brown ear-tick, Rhipicephalus appendiculatus, from the southern lowveld of Zimbabwe. AB - According to the climate-matching model CLIMEX the hot, dry lowveld of Zimbabwe is unsuitable for the survival of the brown ear-tick Rhipicephalus appendiculatus. There is evidence that the tick was absent from the lowveld in the 1960s but was introduced in 1973 and spread over a large area before disappearing in 1983. It was introduced at the start of a wet cycle when, according to CLIMEX predictions, conditions were suitable for its survival, and it disappeared at the end of a dry cycle when conditions were unsuitable. The most important factor in the disappearance of the tick appeared to be heat stress. The study has provided an illustration of the dynamic distribution of R. appendiculatus and field validation of the CLIMEX model. PMID- 2226069 TI - House-dust mite (Pyroglyphidae) populations in mattresses, and their control by electric blankets. AB - A reduction in house-dust-mite populations of 19-84% in beds in regular use could be achieved by heating the mattresses with electric blankets, when the beds were not being slept on. The effect of the heating treatment on the temperature and relative humidity inside the mattress is discussed. House-dust mites in the heated portions of the mattress migrated deeper inside the mattress to a depth of 3.5-5.0 cm. Evidence was also found that house-dust mites in non-heated mattresses do not only live near the surface, but that they are also present deep inside the mattress. PMID- 2226070 TI - Effects of five insect growth regulators on laboratory populations of the North American house-dust mite, Dermatophagoides farinae. AB - The potential of insect growth regulators (methoprene, hydroprene, fenoxycarb, diflubenzuron and triflumuron) to control populations of the North American house dust mite Dermatophagoides farinae (Hughes) was assessed in laboratory bioassays. Methoprene was most effective at suppressing population growth, especially at concentrations of 1.0% (10,000 ppm) and 5.0% (5000 ppm) active ingredient. Hydroprene, structurally related to methoprene, also suppressed house-dust mite populations but not as consistently as methoprene. Fenoxycarb may be effective at controlling house-dust mites but at greater concentrations than were tested. Diflubenzuron and triflumuron, two chitin-synthesis inhibitors, failed to suppress mite numbers and may, in fact, stimulate reproduction in some cases. Almost all concentration of the insect growth regulators were shown to be ineffective when assayed 90 days after treatment. PMID- 2226071 TI - Effect of heat treatments on the house-dust mites Dermatophagoides pteronyssinus and D. farinae (Acari: Pyroglyphidae) in a mattress-like polyurethane foam block. AB - The behaviour and survival of the house-dust mites Dermatophagoides pteronyssinus and D. farinae were studied under laboratory conditions in a mattress-like polyurethane foam block that was heated by an electric blanket. Mites obtained from a laboratory culture were introduced into the foam block which was sliced into seven horizontal layers and covered with an electric blanket. Measurements of temperature and relative humidity were taken between the layers and the number of living mites was established using the heat-escape method. PMID- 2226072 TI - Ultrastructure and distribution of intracellular rickettsia-like microorganisms in various organs of the laboratory-reared adult tick Argas (Persicargas) arboreus (Ixodoidea: Argasidae). AB - Rod (RS) and coccoid (CS) rickettsia-like microorganisms were found in single and group forms in organs of the laboratory-reared adult ticks Argas (Persicarges) arboreus. RS are distributed in most organs but are mainly concentrated in the salivary glands, mid-gut, and testes. CS single forms were concentrated in the rectal sac, while the group forms were limited to Malpighian tubules and haemocytes of both sexes. The primary oocytes were heavily infected with both forms of CS. No RS or CS were detected in the muscles. Despite the structural differences between RS and CS, they are suggested to be different morphotypes of the same organism. PMID- 2226073 TI - Organ culture of ixodid-tick salivary glands. AB - This work describes an organ-culture method for isolated salivary glands of the ixodid tick Amblyomma hebraeum Koch. The support medium is a TC 199-1% agarose gel with no hormonal or undefined supplements. I used a fluid-transport assay for measuring viability of salivary glands. When cultured at 26 degrees C, female glands secreted fluid at 65% on day 2, 59% on day 4 and 42% on day 6 post-culture compared to glands tested on day 0. Fluid secretory rates in culture were higher than rates of glands from partially fed ticks (about 180-250 mg) on days 2, 4 or 6 post-removal from the host. Salivary glands from fed males cultured for 4 days lost only 5% of their fluid secretory competence, whereas glands dissected from males 4 days post-removal lost 63% of their fluid secretory competence. PMID- 2226074 TI - Effect of 20-hydroxyecdysone on the salivary glands of the male tick, Amblyomma hebraeum. AB - Female ticks (Acari: Ixodidae) feed only once in the adult stage, dying after laying a large batch of eggs. During the early post-engorgement stage, haemolymph ecdysteroid titre rises, which is probably responsible for autolysis of the salivary glands that takes place at this time. Males, on the other hand, can re attach and feed numerous times during the adult stage. Males were fed on rabbits for either 7 or 14 days. Haemolymph was collected either the day of removal from the host or 4 days later, and ecdysteroid titre was measured by radioimmunoassay. The approximate titre in all 4 groups was 20 ng of 20-hydroxyecdysone (20-OHE) equivalents/ml haemolymph. Fluid secretory competence in vitro can be used as an index of salivary-gland degeneration. The glands dissected from fed males which had been left off the host for 4 days lost 62% of their fluid secretory competence compared to glands dissected shortly after the males were removed. This loss in fluid secretory competence was reversed by allowing ticks left off the host of 4 days to resume feeding. Male salivary glands lost fluid secretory competence when exposed for 4 days in organ culture to 20-OHE; the effect was maximal at the lowest concentration tested (20 ng/ml). Thus, although male salivary glands were highly sensitive to 20-OHE, it is still not clear whether this hormone causes the tissue to degenerate. PMID- 2226075 TI - Vital signs. PMID- 2226076 TI - Urogenital dysfunction after abdominoperineal resection for carcinoma of the rectum. AB - The long-term urogenital dysfunctions in 46 of 104 surviving patients submitted to abdominoperineal resection for rectal carcinoma between 1972 and 1986 were collected and assessed. Urinary retention was present in 41 percent of the men and 35 percent of women, while incontinence was present in 10 percent of men and 29 percent of women. Impotence was reported by 59 percent of the males, all sexually active before surgery. Dyspareunia was present in 50 percent of the women in the study. The possibility of treating prostatic hypertrophy concurrently with abdominoperineal resection in selected cases to avoid urinary retention is discussed. The limited number of responders to the survey may interfere with the global statistical significance. PMID- 2226077 TI - A critical review of chemical lymph node clearance and staging of colon and rectal cancer at Ferguson Hospital, 1977 to 1982. AB - A unique opportunity to evaluate the method of chemical lymph node clearance for colorectal cancer exists at Ferguson Hospital. Lymph node clearance has been used at the institution since 1977, and this retrospective analysis was undertaken to ascertain its validity there. Furthermore, the node positive group was evaluated to ascertain if the current staging system (Turnbull, 1967) is prognostically accurate for the Dukes' C group. Specifically evaluated for possible prognostic variance was the survival of those patients whose tumors demonstrated partial bowel wall penetration and only one to four positive nodes, a "C1 subset," previously reported to have favorable prognosis. Eight hundred sixty-four cases of colon and rectal cancer treated surgically from 1977 to 1982 were analyzed. There was a mean of 27 lymph nodes retrieved per specimen and a mean of 4.5 positive nodes per Dukes' C specimen. There were 43 C1 and 201 C2 cases with five year survival rates of 73 and 38 percent, respectively. The results of chemical clearance at Ferguson Hospital were found to be comparable with that of other centers using chemical clearance and superior to hand dissection. The C1 subset clearly is noted to have prognostic advantage and should occupy a separate designation in any staging system. PMID- 2226078 TI - Colonoscopic screening of asymptomatic patients with a family history of colon cancer. AB - The records of 201 asymptomatic patients who underwent colonoscopy based solely on a family history of colon cancer were reviewed. Eighty-five patients (42 percent) had a total of 166 lesions. Fifty-four (27 percent) patients of the screened population had neoplastic lesions, while 31 (15 percent) patients had nonneoplastic polyps. Four carcinomas were found. Twenty-five of the patients with polyps (29 percent) had no polyps distal to the splenic flexure; these proximal polyps (and two carcinomas) would have been missed on screening with fiberoptic sigmoidoscopy. Nineteen of these 25 patients had polyps smaller than 0.5 cm, which likely would have been missed with contrast enemas. Almost one half (47 percent) of all polyps discovered at screening colonoscopy were proximal to the descending colon. Only one patient younger than 40 years old had adenomas. The yield of polyps and cancer in patients with familial risk indicates screening colonoscopy should be considered after age 40. PMID- 2226079 TI - A randomized trial comparing direct current therapy and bipolar diathermy in the outpatient treatment of third-degree hemorrhoids. AB - Fifty patients with third-degree hemorrhoids were randomized to receive outpatient treatment with either bipolar diathermy or direct current therapy. Direct current therapy was used to treat 26 patients and bipolar diathermy was used to treat 24 patients. Twenty patients in each group were successfully treated as judged by resolution of symptoms and shrinkage of hemorrhoidal tissue. Both treatments are effective in the outpatient management of large, prolapsing hemorrhoids. Bipolar diathermy is less time consuming and better tolerated. PMID- 2226080 TI - Perirectal abscess in Crohn's disease. Drainage and outcome. AB - The role of surgical intervention in the treatment of patients with anorectal Crohn's disease is controversial. To clarify the success of aggressive drainage and the subsequent clinical course of patients with Crohn's disease and perirectal abscesses, the authors reviewed the records of 38 patients who presented with this condition during an eight-year period. Twenty-two male and 16 female patients (median age, 32 years; range, 17 to 61 years) with clinically or pathologically confirmed Crohn's disease of the bowel underwent operation for perirectal abscesses. Thirty-two percent of patients had no previous history of anorectal Crohn's disease. Thirty simple abscesses and 8 complex horseshoe abscesses were treated. At operation, 53 percent of patients underwent incision and drainage whereas 26 percent received loop indwelling drains and 21 percent had mushroom catheters placed. After resolution of the index abscess, recurrent abscesses occurred in 45 percent of the patients who underwent catheter drainage and 56 percent of the patients who underwent incision and drainage. More importantly, 44 percent of the incision and drainage group and only 31 percent of the catheter drainage group required subsequent proctectomy to control perineal sepsis. The healing time of the perineal wound was longer than six months in 83 percent of patients requiring rectal excision. We concluded that long-term catheter drainage may offer substantial benefit in the overall outcome of the treatment of patients with Crohn's disease and perirectal abscess. PMID- 2226081 TI - Survival in patients with large-bowel cancer. A population-based investigation from the Melbourne Colorectal Cancer Study. AB - Five-year survival data were obtained in 97 percent or 1105 of 1140 new patients with histologically confirmed colorectal adenocarcinoma during a 12-month period in 1981 and 1982, as part of a large comprehensive population-based study of colorectal cancer incidence, etiology, and survival, The Melbourne Colorectal Cancer Study. Fifteen percent of patients were Dukes' A stage, 32 percent were Dukes' B, 25 percent were Dukes' C, and 29 percent were Dukes' D. At five years after diagnosis, the observed survival rate was 36 percent and the adjusted rate was 42 percent. Dukes' staging was a highly discriminating factor in survival (P less than 0.001). Survival rates were better in women than in men and better for patients with colon cancer than for patients with rectal cancer. Survival by Dukes' staging was not affected by colon subsite or by the tumor being the first and single tumor, metachronous tumor, or synchronous tumor. The survival of younger patients was better for Dukes' stages A, B, and C, and worse for Dukes' D. Survival was worse in the presence of bowel perforation in Dukes' C and D stages. Within Dukes' D (incurable cases), survival was best in the absence of hepatic metastases, slightly worse when only hepatic metastases were present, and poorest in the presence of both hepatic and extrahepatic metastases. Statistical modeling of survival determinants other than staging indicated that cell differentiation had the largest effect (survival decreasing with poor cell differentiation), followed by site (survival worse for rectal cancer than colon cancer), then age (survival better for younger patients), while bowel perforation had the smallest effect on survival. PMID- 2226082 TI - The surgical management of children with ulcerative colitis. The old vs. the new. AB - The authors' experience with children who have chronic ulcerative colitis was reviewed to compare their current surgical approach (ileoanal anastomosis) with earlier methods of management. Between 1960 and 1984, 137 children with chronic ulcerative colitis underwent surgery (mean duration of follow-up, 7.1 years). In 91 patients, the procedures were a total proctocolectomy with ileostomy or Kock pouch (66) or a lesser colectomy with either an ileostomy (16) or an ileorectal anastomosis (9) (group I). Forty-six patients underwent an ileoanal anastomosis procedure (group II). Children in group I were more likely to have significant preoperative loss of weight, a debilitated condition, and malnutrition. Urgent or emergency surgical intervention was required in 25 percent of patients in group I but in only 4 percent of patients in group II. Trends included 1) a younger age at operation in group II, 2) a higher mortality in group I (7.7 percent) than group II (0 percent), and 3) a higher perioperative mortality with emergency operations (23 percent) than elective procedures (1.6 percent). In group I, 98 percent of patients had an abdominal ostomy, but no patients in group II had an abdominal ostomy. The children with an ileoanal anastomosis had an average of 4.8 stools during waking hours and 1.3 stools each night. On the basis of this experience, the authors recommend use of the ileoanal anastomosis procedure in the surgical treatment of chronic ulcerative colitis in children. PMID- 2226083 TI - Accumulation and pepsin solubility of collagens in the bowel of patients with Crohn's disease. AB - The collagen content of resected strictured intestine, with and without fistulas, from patients with Crohn's disease has been compared with that in macroscopically normal intestine removed from the same patients and from others without inflammatory bowel disease. Collagen content per unit wet or dry weight of tissue was significantly increased in all grossly diseased tissue whether fistulated or not. Although there was a significant increase in collagen types I, III, and V in diseased tissue, the relative proportions of major collagen types extracted by limited pepsin digestion were similar for both Crohn's and non-Crohn's intestine (type I, 65 to 70 percent; type III, 25 to 30 percent; type IV, 2 to 3 percent; and type V, 2.5 to 3 percent). CNBr digestion of pepsin insoluble material showed a similar relative abundance of types I and III, indicating no major change in collagen type distribution between older (insoluble) and more newly synthesized collagen. There was no evidence of the presence of type I trimer collagen. Type VI collagen, although not quantitated, was observed in 70 percent of intestinal specimens. The proportion of total collagen solubilized by pepsin treatment was significantly greater in both grossly diseased and macroscopically normal Crohn's bowel compared with non-inflammatory bowel disease bowel. These findings suggest that there are disturbances of collagen metabolism in Crohn's intestine, which account for the stricturing process and which may predate gross pathologic changes. PMID- 2226084 TI - Endometrioma. An intra-abdominal troublemaker. AB - A ten-year review of intestinal and abdominal wall endometriomas is reported. Seven cases of intestinal and two cases of abdominal wall endometriomas are presented. Symptoms were varied but a majority had some gynecologic complaint. In this select group of patients, preoperative investigations did not assist in establishing the diagnosis. All patients underwent surgery and coexisting inflammatory bowel disease was present in two patients. This review suggests that endometrioma of the intestine requires a high index of suspicion for diagnosis and that danazol does not appear to be effective treatment for these patients. PMID- 2226085 TI - Enteroglucagon and peptide Y-Y response after construction of a pelvic reservoir in humans. AB - The results of an investigation of plasma levels of gastrointestinal hormones in patients after the construction of a pelvic reservoir are reported. Enteroglucagon (EG) and peptide tyrosine-tyrosine (PYY), two hormones believed to play a relevant role in the adaptive response to bowel resection, were investigated using a specific radioimmunoassay in basal conditions and after a standard meal. Pouch patients showed a statistically significant increase in basal levels of both enteroglucagon and PYY compared with control subjects (P less than 0.02 and P less than 0.001, respectively). The response of enteroglucagon to food ingestion, evaluated by means of the total integrated response, was similar in patients and controls. Conversely, the response of PYY was significantly increased in pouch patients compared with control cases (P less than 0.02). Results of this investigation suggest that gut hormones may be involved in mediating the adaptive response of the intestine to pouch construction. Changes of gut peptides may explain, at least in part, the functional results observed after pouch construction. PMID- 2226086 TI - Retroperitoneal air after routine hemorrhoidectomy. Report of a case. AB - Retroperitoneal air as a complication after routine hemorrhoidectomy has not been reported in the literature. This occurred recently after hemorrhoidectomy in a 34 year-old patient receiving glucocorticoid therapy for rheumatoid arthritis. Adverse steroidal effects of wound healing have been well documented. It is believed that steroid-induced tissue changes contributed to the development of this unique complication. PMID- 2226087 TI - Association of anterior ectopic anus and partial absence of levator musculature in a woman with impaired defecation. Report of a case. AB - A 25-year-old nulliparous woman with adult onset constipation and slight anterior displacement of the anus underwent pelvic magnetic resonance imaging and was diagnosed with congenital hemiabsence of the levator ani sling. Impaired defecation was confirmed by anorectal function studies and defecography demonstrated an anterior rectocele, perineal descent at the upper limit of normal, and partial obstruction of defecation, which appeared related to the levator sling abnormality. To our knowledge, this combination of findings has not been previously described as a cause of adult onset constipation. PMID- 2226088 TI - Colonic lipoma as a source of massive hemorrhage. Report of a case. AB - Colonic lipomas are a rare source of massive lower gastrointestinal bleeding requiring operative intervention. A case of massive hemorrhage from cecal lipomatosis is presented. The methods of preoperative diagnosis and treatment are discussed. PMID- 2226089 TI - Malignant potential of juvenile polyposis coli. Report of a case and review of the literature. AB - Juvenile polyps of the colon and rectum traditionally have been viewed as being benign inflammatory or harmartomatous lesions without potential for malignant change. The authors report a case of adenocarcinoma developing in a patient with sporadic juvenile polyposis. Juvenile polyposis was diagnosed in the patient at age 4 years. He underwent subtotal colectomy at age 6 years. At age 12, he underwent a proctectomy and a Swenson pull-through because of adenomatous changes in the rectal stump. At age 19 surveillance endoscopy revealed invasive cancer in a juvenile polyp. PMID- 2226090 TI - Yersinia enterocolitica abscess of the transverse colon. Report of a case. AB - Yersinia enterocolitica abscess of the bowel is a rare entity. Only five cases have previously been reported--none in the surgical literature. A unique presentation for Yersinia infection, abscess of the transverse colon, is described, and the literature of Y. enterocolitica intestinal perforation and abscess is reviewed. PMID- 2226091 TI - Ileocolic nipple valve anastomosis for preventing recurrence of surgically treated Crohn's disease. Long-term follow-up of six patients. AB - To prevent coloileal reflux after ileocecal resection, an ileocolic nipple valve anastomosis was constructed in six patients with Crohn's disease. The patients were observed for more than 7 years and were compared with 21 Crohn patients in whom conventional end-to-end ileocolic anastomosis was performed during the same period. The outcome was more favorable in the group with nipple valve anastomosis, i.e., longer interval between surgery and symptomatic relapse, and tendency to less frequent recurrence and re-resection. An association was found between radiologically preserved nipple valve and remission, and two patients with intact valve at long-term follow-up remained symptom-free. The observations implied that protection of the terminal ileum from coloileal reflux after ileocecal resection for Crohn's disease may favorably influence the prognosis. PMID- 2226093 TI - Gastric contents retained in rat stomach following mild irritant exposure contribute to adaptive cytoprotection. AB - Fluid retained in the gastric lumen immediately preceding the administration of a damaging product will dilute that product and decrease its injurious capacity. In an attempt to explain the phenomenon of adaptive cytoprotection, we studied the effect of mild irritant exposure on the volume of fluid retained in the gastric lumen. Rats treated with 0.2 N-0.4 N HCl had a larger volume of gastric fluid retained as compared to animals treated with 0.4 N NaCl. Additionally, a mixture of gastric juice derived from rats exposed to 0.4 N HCl with 2 ml ethanol was significantly less damaging to the gastric mucosa than a similar mixture containing an equal volume of gastric juice derived from 0.4 N NaCl-exposed rats. We conclude from our observations that in mild irritant-exposed stomachs, the gastric juice is a main contributor to the protection against ethanol injury. PMID- 2226092 TI - Putative mechanisms of cytoprotective effect of certain antacids and sucralfate. AB - An investigation of cytoprotective activity of certain antacids and inert particles was carried out by treating ethanol-induced gastric mucosal damage in rats in order to clarify possible mechanisms by which aluminum-containing antacids act. Al(OH)3 inhibited gastric mucosal damage in a dose-related and time dependent manner. Neither aluminum ions themselves nor the particle size of the Al(OH)3 complex were responsible for the observed cytoprotection, since neither AlCl3, chemically inert Al2O3*C, nor sea sand showed protective effects. Hyperosmolality in the gastric lumen was not a deciding factor in inducing cytoprotection. Silicic acid and titanium dioxide, with superficial charge similar to Al(OH)3 proved to be effective in inhibiting gastric hemorrhagic lesions and releasing PGE2, suggesting that the surface charge of Al(OH)3 may be important in its cytoprotective properties. The same may also be valid for sucralfate. Since antacid-induced cytoprotection was only partly reduced by pretreatment with indomethacin, it is likely that additional mechanisms and mediators other than prostaglandins, such as nonprotein sulfhydryls, also are involved in gastric cytoprotection arising from aluminum-containing antacids. PMID- 2226094 TI - Modulatory action of adenosine on gastric function and ethanol-induced mucosal damage in rats. AB - This study examines the gastric effects of adenosine and its antagonist, theophylline, on secretory function, mucosal blood flow, and on ethanol-induced glandular mucosal damage in rats that were fasted for 24 hr before experimentation. The animals were anesthetized with sodium pentobarbitone (50 mg/kg intraperitoneal) and their tracheae cannulated. An ex vivo stomach chamber then was prepared. The luminal bathing solution was collected every 15 min and the concentrations of H+ and Na+ were determined by a pH autotitrator and an ionmeter, respectively. The glandular mucosal blood flow was measured by a laser Doppler flowmeter and the severity of lesions was determined by measuring the hemorrhagic areas. Adenosine administration (2.5 or 7.5 mg/kg, subcutaneous) markedly lowered the H+ and Na+ output but increased the secretory volume and mucosal blood flow in a dose-dependent manner. The same doses of the nucleoside also prevented ethanol-induced mucosal damage. These effects were prevented by pretreatment with theophylline (30 or 60 mg/kg, subcutaneous). Ethanol given alone significantly depressed the H+ and Na+ secretion. Both effects were not modified by adenosine treatment. However, the depressive action of ethanol on mucosal blood flow was prevented by adenosine. These findings indicate that adenosine modulates the physiological function of the stomach. It also directly activates the defensive mechanism of the stomach, which is partially mediated by the improvement of the gastric mucosal blood flow and an increase in the nonacid component of gastric secretion. PMID- 2226095 TI - Early gastric cancer. Endoscopic diagnosis of depth of invasion. AB - In order to decide on a treatment strategy against gastric cancers, an accurate preoperative evaluation of the depth of cancer invasion is essential. Preoperative endoscopic diagnosis of the depth of invasion was compared with pathological results of the resected specimen in 206 early gastric cancers and 32 early-like advanced gastric cancers. The endoscopic distinction between early and early-like advanced cancers was correctly made in 83.6% of the cases. Among the early gastric cancers, mucosal and submucosal invasion was correctly presumed in 71.9% of the cases. When the tumor was an elevated type, or located in the antrum, the endoscopic diagnosis tended to be deeper than the true depth. The size of tumor contributed little to the depth diagnosis. Pathomorphological changes on the tips of converging folds were the important clue for diagnosing depth. PMID- 2226096 TI - Measurement of gastric emptying rate in humans. Simplified scanning method. AB - Simultaneous measurements of the gastric emptying rate of the solid and liquid phase of a dual-isotope-labeled test meal were made using a gamma camera and a simple scintillation detector, similar to that used in a hand-held probe. A simple scanning apparatus, similar to that used in a hand-held scintillation probe, was compared with simultaneous measurements made by a gamma camera in 16 healthy males. A dual-labeled test meal was utilized to measure liquid and solid emptying simultaneously. Anterior and posterior scans were taken at intervals up to 120 min using both a gamma camera and the scintillation probe. Good relative agreement between the methods was obtained both for solid-phase (correlation range 0.92-0.99, mean 0.97) and for liquid-phase data (correlation range 0.93 0.99, mean 0.97). For solid emptying data regression line slopes varied from 0.75 to 1.03 (mean 0.84). Liquid emptying data indicated that slopes ranged from 0.71 to 1.06 (mean 0.87). These results suggested that an estimate of the gamma measurement could be obtained by multiplying the scintillation measurement by a factor of 0.84 for the solid phase and 0.87 for the liquid phase. Correlation between repeat studies was 0.97 and 0.96 for solids and liquids, respectively. The application of a hand-held probe technique provides a noninvasive and inexpensive method for accurately assessing solid- and liquid-phase gastric emptying from the human stomach that correlates well with the use of a gamma camera, within the range of gastric emptying rate in the normal individuals in this study. PMID- 2226097 TI - Evaluation of antral mast cells in nonulcer dyspepsia. AB - Two hundred twenty-five patients with the symptoms of nonulcer dyspepsia underwent clinical and endoscopic evaluation including histologic assessment of endoscopic biopsies. Mast cells were counted after special staining with low pH Alcian blue. Of 225 patients, 31 (13%) were found to have 11 or greater mast cells per high-power field. Endoscopic and routine histologic findings were similar between the subset of 31 patients with 11 or more mast cells and the entire group of 225. The 31 patients with increased antral mast cells had failed treatment with standard drug used for peptic ulcer disease. H1-antagonists improved symptoms in the majority of patients (79%) in whom we had adequate follow-up. Patients with increased mast cells on antral biopsy appear to be subset of patients with nonulcer dyspepsia amenable specific treatment with H1 antagonists. PMID- 2226098 TI - Cholecystokinin stimulates growth of human pancreatic adenocarcinoma SW-1990. AB - The effect of a synthetic analogue of CCK (Thr4,Nle7CCK-9) on growth of SW-1990 human pancreatic cancer was examined in two experimental models. Nude mice bearing SW-1990 pancreatic cancer xenografts were injected with CCK (5, 15, or 25 micrograms/kg) or vehicle twice daily for 20 days. Animals were then sacrificed and tumor volume, weight, protein, and deoxyribonucleic acid (DNA) content were evaluated. SW-1990 cells were grown in vitro and the effects of CCK, secretin, vasoactive intestinal peptide (VIP), and proglumide (a CCK-receptor antagonist) on cell number and DNA synthesis were determined. The highest dose of CCK, 25 micrograms/kg, significantly increased tumor weight, protein content, and DNA content (P less than 0.005). In vitro, CCK caused significant increases in cell counts of up to 47% at six days and 66% at 12 days compared to control. Graded concentrations of CCK had a biphasic effect on DNA synthesis with significant increases of up to 65% (P less than 0.005). CCK-induced cell proliferation was inhibited by proglumide. Secretin slightly increased cancer cell growth, although not as potently as CCK, VIP or secretin in combination with CCK did not show potentiation. These results indicate that growth of some human pancreatic cancers may be influenced by gastrointestinal peptides, of which CCK is the most potent. PMID- 2226099 TI - Improved scintigraphic assessment of severe cholestasis with the hepatic extraction fraction. AB - In previous studies, we found that biliary scintigraphy with technetium-99m labeled iminodiacetic acid ([99mTc]IDA) provided excellent discrimination between intrahepatic and extrahepatic cholestasis, except in patients with profound cholestasis who had poor visualization of the biliary tree. In this study, we have used deconvolution analysis to determine the hepatic extraction fraction (HEF) of a hypothetical single circulatory pass of [99mTc]IDA. Our hypothesis was that extraction of radionuclide from the blood would be normal in patients with extrahepatic obstruction alone, but would be impaired in patients with intrahepatic disease (IHD). The purpose of this study was to compare the HEF in patients with profound cholestasis (bilirubin greater than or equal to 3.0 mg/dl) due to either IHD or common bile duct obstruction (CBDO). Normal subjects (N = 13) had an HEF of 100%. Patients with CBDO (N = 13) had slightly reduced HEF values (92.8 +/- 3.2%) despite profound hyperbilirubinemia (6.1 +/- 1.0 mg/dl). Patients with IHD (N = 23) had a markedly reduced HEF (43.1 +/- 4.1%) which was significantly lower than patients with CBDO and normal subjects (P less than 0.001). We conclude that the determination of the HEF during biliary scintigraphy is helpful in distinguishing between intrahepatic and extrahepatic disease in patients with hyperbilirubinemia (bilirubin greater than or equal to 3.0 mg/dl). PMID- 2226100 TI - Effect of race upon organ donation and recipient survival in liver transplantation. AB - The effect of the race of the donor on organ donation and on the outcome of clinical liver transplantation has not been addressed previously. The aims of this study were to determine: (1) the number of organs donated by each of the major racial groups of the United States, (2) the outcome of transplantation of these organs across racial groups, and (3) the pattern of liver disease that required transplantation in each of these racial groups. A significantly higher proportion of organs were donated by white non-Hispanic Americans than either black or Hispanic Americans. There was no significant difference in survival when an organ was transplanted between black and white Americans and vice versa. Postnecrotic cirrhosis from a variety of causes was the most common indicator affecting black and white recipients, while primary biliary cirrhosis and primary sclerosing cholangitis were uncommon in the black population. While the number of organs donated by blacks was low, it was, however, proportional to the number of black recipients in this study. Reasons for the low rate of donation by the black and white Hispanic population are discussed. It is concluded that race is not a criteria to be used in selection of donors for liver transplantation. Educational programs addressing issues of organ donation and transplantation directed towards the black and Hispanic populations are recommended. PMID- 2226101 TI - Short-term effect of hepatic arterial versus portal venous reperfusion on energy levels of liver tissue. AB - The hepatic artery and the portal vein blood vary in flow, oxygenation, and hormonal content. It was uncertain which blood supply has a greater effect on the recuperative process of the hepatocytes in the ischemic liver during the initial reperfusion. The ability of the liver cells to restore its energy phosphates is related to the viability of the liver. This study was designed to determine the differences of the high energy phosphate in the liver predicated upon whether reflow was first provided by either the hepatic artery or the portal vein followed by subsequent reperfusion from both vessels. The recovery of ATP upon 10 min of only hepatic arterial reperfusion after 15 min of total ischemia was much slower compared to the portal venous reperfusion only. It may be undesirable, therefore, to reperfuse the liver with hepatic arterial blood first immediately after warm liver ischemia. PMID- 2226102 TI - Cirrhosis of the liver. A risk factor for development of cholelithiasis in males. AB - An ultrasonographic study about the prevalence of cholelithiasis was performed in 410 cirrhotic patients and in 414 controls matched for age and sex. Gallstone disease was found more often in cirrhotic patients (31.9%) than in controls (20.7%) (P less than 0.001). The female-to-male ratio of gallstones prevalence in cirrhotic patients approached to 1:1. Gallstone disease in cirrhotic patients vs controls was significantly higher (30.2% vs 16.5%) (P less than 0.001) in males only. No difference was found, for gallstone disease prevalence in cirrhosis of different etiology. The prevalence of cholelithiasis increased from Child's A to Child's C with a significant trend (P less than 0.001); this difference was significant in males (12.3% vs 40.5%) (P less than 0.001) but not in females. This study shows that cirrhosis represents a risk factor for the development of cholelithiasis in males. We suggest that high levels of estrogens could play a role in these patients, by an impairment of gallbladder emptying similar to that observed in pregnant women. PMID- 2226104 TI - Diagnosis of metastatic lesions to the stomach by salvage cytology. A report of three cases. AB - Secondary neoplasms of the stomach are rare and are often clinical and diagnostic problems. Three patients with bleeding "volcano-like" ulcers were diagnosed by combined endoscopic "salvage" cytology and surgical biopsy as having metastatic submucosal lesions from hematologic spread. The combination of endoscopic appearance, clinical findings, and tissue and cytologic examination can lead to the correct diagnosis. The results from these cases support the utility of this cytologic technique in combination with biopsy in this clinical setting. PMID- 2226103 TI - Prospective study of alcohol intake and large bowel cancer. AB - The alcohol intake of a cohort of Japanese men in Hawaii is directly and significantly related to the risk of developing rectal cancer, whether assessed on the basis of amount consumed or as a percent of total calories. Wine and whiskey are directly related to rectal cancer, but beer is the only alcoholic beverage that displays a statistically significant dose-response (P = 0.008). Colon cancer risk also is related directly to alcohol intake, but the association is statistically significant only when measured as a percent of energy intake. This suggests that alcohol might displace cancer inhibitors from the diet. Calcium, vitamin C, and dietary fiber are inversely related to colon cancer risk in this cohort, and each of these micronutrients displays statistically significant negative correlation with alcohol intake. A possible positive association between alcohol and lung cancer was ruled out after adjusting for cigarette smoking. Cancers of the prostate and stomach were unrelated to alcohol intake, but the risk of acquiring cancer at all other sites combined was strongly related to alcohol intake. PMID- 2226105 TI - Primary non-Hodgkin's T-cell lymphoma of the esophagus. A case with peculiar endoscopic ultrasonographic pattern. AB - We report a case of primary esophageal non-Hodgkin's T-cell lymphoma in a young white female. At admission, endoscopy revealed large, irregularly shaped, esophageal ulcerations with super imposed candidiasis. Endoscopic ultrasonography to assess submucosal alterations and periesophageal involvement revealed a diffuse hypoechogenic thickening (up to 5 mm) of the esophageal wall, a pattern consistent with lymphomatous infiltration. Definitive diagnosis was made with the aid of histology and immunohistochemistry. PMID- 2226106 TI - Small bowel phytobezoar mimicking presentation of Crohn's disease. AB - A case of small bowel phytobezoar formed from unusual ingested vegetation is described. The patient presented with recurrent subacute obstruction and a right iliac fossa mass mimicking the presentation of Crohn's disease. None of the usual gastrointestinal disorders that predispose to bezoar formation were present. The phytobezoar passed spontaneously following small bowel enema and colonoscopy. It is possible that relaxation of the gut secondary to the antispasmodics administered at investigation or the physical disturbance during these procedures enabled migration through the ileocecal valve. Antispasmodics may be of use in the conservative management of bezoars obstructing otherwise normal bowel. PMID- 2226107 TI - Sulfhydryls protect patients against complications of erosive gastritis. PMID- 2226108 TI - Insulin use in NIDDM. Rationale based on pathophysiology of disease. AB - Because basal hyperglycemia is a major feature in non-insulin-dependent diabetes mellitus, diabetes control can be monitored by the fasting blood glucose concentration. A hierarchical sequence of therapies is proposed in which the major aim is to maintain near-normal fasting blood glucose concentrations, in the expectation that this will help prevent development of long-term complications. When diet and tablet therapy are no longer effective in keeping the fasting blood glucose level less than 6 mM, a basal insulin supplement from a long-acting insulin such as ultralente can be added. When monitored by fasting blood glucose concentration, there is little risk of hypoglycemia, and the patient can continue a normal life-style without restrictions concerning exercise or the size of individual meals. A basal insulin supplement does not induce marked weight gain. The dose of insulin required can be predicted from the level of the fasting blood glucose and the degree of obesity, which provides an index of the accompanying insulin resistance. Based on current evidence, insulin therapy is equally appropriate in patients with insulin deficiency and insulin resistance, because the benefit from maintaining near-normal glucose concentrations probably outweighs a putative risk of hyperinsulinemia. In more severely affected patients, additional regular insulin to cover meals is needed. Lowering fasting blood glucose to normal with a basal insulin supplement reduces endogenous insulin production, and this may be advantageous if accompanying production of islet amyloid polypeptide and islet amyloid formation are also reduced. PMID- 2226109 TI - Insulin administration via liposomes. AB - Liposomes have been used in insulin therapy as a means to selectively target insulin to the liver, enhance oral absorption of insulin, and prolong insulin action. Liposomes are an effective means of delivering insulin specifically to hepatocytes. The usefulness of hepatically targeted liposomes in the treatment of diabetes is restricted due to the requirement that they be given intravenously, the dilute concentration of insulin present in liposomal preparations, and the cost associated with liposome production. Encapsulating insulin in liposomes results in enhanced oral absorption of insulin. The high doses of liposome entrapped insulin required perorally, coupled with extreme variability in the glycemic response to peroral liposomes, limits the value of peroral liposomal insulin as a viable diabetic therapy. Insulin action can be sustained via encapsulation of insulin in liposomes given subcutaneously. Most insulin appears to remain at the injection site, and the presence of a lipid matrix for subcutaneous insulin delivery raises concerns over enhanced antigenicity of liposomal insulin given subcutaneously. Viewed in the light of the limitations outlined above, the contribution of liposomal insulin to understanding and treatment of diabetes mellitus will probably be via use of hepatically targeted liposomes as a pharmacological probe to decipher the role of the liver in the metabolic complications associated with diabetes mellitus. PMID- 2226110 TI - Monomeric insulins and their experimental and clinical implications. AB - Due to the inherent pharmacokinetic properties of available insulins, normoglycemia is rarely, if ever, achieved in insulin-dependent diabetic patients without compromising their quality of life. Subcutaneous insulin absorption is influenced by many factors, among which the associated state of insulin (hexameric) in pharmaceutical formulation may be of importance. This review describes the development of a series of human insulin analogues with reduced tendency to self-association that, because of more rapid absorption, are better suited to meal-related therapy. DNA technology has made it possible to prepare insulins that remain dimeric or even monomeric at high concentration by introducing one or a few amino acid substitutions into human insulin. These analogues were characterized and used for elucidating the mechanisms involved in subcutaneous absorption and were investigated in preliminary clinical studies. Their relative receptor binding and in vitro potency (free-fat cell assay), ranging from 0.05 to 600% relative to human insulin, were strongly correlated (r = 0.97). In vivo, most of the analogues exhibited approximately 100% activity, explainable by a dominating receptor-mediated clearance. This was confirmed by clamp studies in which correlation between receptor binding and clearance was observed. Thus, an analogue with reduced binding and clearance gives higher circulating concentrations, counterbalancing the reduced potency at the cellular level. Absorption studies in pigs revealed a strong inverse correlation (r = 0.96) between the rate of subcutaneous absorption and the mean association state of the insulin analogues. These studies also demonstrated that monomeric insulins were absorbed three times faster than human insulin. In healthy subjects, rates of disappearance from subcutis were two to three times faster for dimeric and monomeric analogues than for human insulin. Concomitantly, a more rapid rise in plasma insulin concentration and an earlier hypoglycemic response with the analogues were observed. The monomeric insulin had no lag phase and followed a monoexponential course throughout the absorption process. In contrast, two phases in rate of absorption were identified for the dimer and three for the normal hexameric human insulin. The initial lag phase and the subsequent accelerated absorption of soluble insulin can now be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process. In the light of these results, the effects of insulin concentration, injected volume, temperature, and massage on the absorption process are now also understood.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2226111 TI - Devices for insulin administration. AB - There is a significant need for revised, safe, and more effective insulin delivery methods than subcutaneous injections in the treatment of both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes. The aim of this review is to describe the rationale and methods for better use of injection and infusion devices for intensive insulin therapy and to describe results of animal and human research that will lead to an implantable artificial pancreas. Injection devices, e.g., jet injectors, insulin pens, and access ports, cannot be considered as a major breakthrough in the quest for improved control, although they may improve the patient's comfort. External pumps have benefits over multiple injections and conventional insulin therapy only in specific subgroups of patients, e.g., those with recurrent severe hypoglycemia, but only when used by experienced personnel. The external artificial pancreas (Biostator) is also to be used by experienced personnel for limited clinical and research applications, e.g., surgery of the diabetic patient. The development of an implantable version of the artificial pancreas is linked to progress in the field of reliable long duration glucose sensors. Finally, programmable implantable insulin pumps, used as an open-loop delivery system, are the most promising alternative to intensive subcutaneous insulin strategies in the short term, although clear evidence of improved safety and efficacy remains to be documented. PMID- 2226112 TI - Role of insulin in management of surgical patients with diabetes mellitus. AB - Because surgery is a likely event during the lifetime of patients with diabetes, health-care team members need to be aware of the metabolic problems that may occur during the perioperative period. Surgery, especially in the presence of general anesthesia, will produce a diabetogenic response. This is generally due to an elevation of counterregulatory hormones, although endogenous insulin is also suppressed. The excessive lipolysis and ketogenesis that can occur during surgery can have particularly deleterious effects for patients with diabetes. Thus, sufficient insulin must be provided during this period to suppress these catabolic processes. The major controversy regarding surgery and diabetes concerns the route of insulin administration. This article reviews the various treatment options for patients with insulin-dependent and non-insulin-dependent diabetes mellitus, with particular emphasis on the role of insulin. Special situations, e.g., outpatient surgery, coronary artery bypass, and emergency surgery, are also discussed. PMID- 2226113 TI - Natural history of beta-cell dysfunction in NIDDM. AB - Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and beta-cell dysfunction. This review focuses on the beta-cell, what defects occur when and why. Two major anatomic observations have been made in NIDDM. The beta-cell mass is mildly reduced, especially when obesity is taken into account. Also, amyloid deposits are frequently observed in the islets. It is unclear whether these changes are genetically mediated or result secondary to the loss of glucose homeostasis. Many studies have looked at some aspect of insulin secretion in NIDDM, and two types of distinct abnormalities have been described. Early on, there is a marked disruption in pulsatile insulin delivery, which is potentially an important contributor to the insulin resistance. It is unclear whether the loss of pulsatile delivery is acquired or genetically induced. Later, after glucose intolerance has started, several other secretory abnormalities develop coincident with loss of beta-cell glucorecognition. The net result is further deterioration in timing of insulin delivery and postprandial hyperglycemia. A second important consequence of the glucose blindness is that the inherent compensatory beta-cell mechanisms that guard against hyperglycemia are bypassed. We propose that the loss of glucose responsiveness is a direct result of an elevated glucose concentration (so-called glucotoxicity) and have generated substantial data in rat models that support this idea. The logical conclusion is that beta-cell function in NIDDM can be maximized by achieving the best metabolic control possible. PMID- 2226114 TI - TCI left ventricular assist device: nursing implications. AB - The use of left ventricular devices as a bridge to transplantation has gained considerable acceptance in transplant centers nationwide. A new, innovative assist device that allows for greater patient mobility with a decreased incidence of patient complications is now being used at St. Luke's Episcopal Hospital to support the potential transplant recipient while waiting for a donor heart. The authors discuss the pathophysiology related to this type of assist device, along with two case studies and the nursing diagnoses indicated for patients using this unique device as a bridge to transplant. PMID- 2226115 TI - Intravenous amrinone therapy: nursing implications. AB - Intravenous amrinone (Inocor) is the latest in a line of cardiotonic agents approved for the treatment of heart failure. A thorough knowledge of the pharmacology of this agent is essential in the development of a plan of care for this critically ill patient. PMID- 2226116 TI - Needs of parents of critically ill children. AB - When a child becomes critically ill, stable patterns of parental routines are changed. Although the resulting stress on parents has long been recognized by clinicians, only recently has research addressed parental needs during a child's illness. PMID- 2226117 TI - Attitudes of critical care nurses toward organ donation. AB - In October, 1987, federal legislation requiring hospitals to develop protocols to encourage organ and tissue donation went into effect. Despite required request legislation, a lack of donors still exists. The attitudes of the critical care nurses caring for potential organ donors may have an effect on the actual donation of organs. This author describes how knowledge level and experience with organ donors and recipients affected the attitudes of two groups of critical care nurses towards organ donation. PMID- 2226118 TI - Critical care RN student elective: a recruitment approach. AB - Recruiting experienced RNs into critical care is a valuable goal. In this article, the authors describe a senior year critical care nursing elective for registered nurse students in a BSN completion program entirely developed and presented by nursing service personnel. This program increases the exposure of RNs to critical care as a specialty which they might want to continue after graduation. PMID- 2226119 TI - Peripheral sympathetic neuropathy evaluated by recording the evoked electrodermal response using an impedance reactometer. AB - Autonomic nervous dysfunction was indirectly evaluated on the basis of the skin electrical resistance relative variation (SERV), recorded by our recently developed system, with two pairs of surface electrodes placed on the palm and on the sole of the foot, after the application to the subject of a sensory stimulus (sound 60 dB, 860 Hz, 0.5 s duration) or in the course of a Valsalva manoeuvre. The results were digitally measured and recorded on thermosensitive millimetric paper analysing the following parameters: latency (LT), i.e. the time interval(s) between application of the stimulus and onset of SERV, both at palm (LTh) and foot (LTf); amplitude of the response (mm) recorded and evaluated in the form of SERV; velocity of the response as rate of time change (Vr) and autonomic conduction velocity, -ACV (m/s), calculated by the height/LT ratio. The present study refers to a group of 60 diabetic patients: 32 F/28 M; mean age +/- SD 46.8 +/- 11.8 years; 29 insulin-dependent, 21 non-insulin-dependent; duration of diabetes 8.6 +/- 4.6 years. The data were compared to those recorded in a group of 50 nondiabetics (22 F/28 M; mean age 47.5 +/- 14.1 years) who were apparently healthy. A significant statistical difference (P less than 0.001) was found between diabetic patients and controls for all studied parameters: LTh (s) 2.65 +/- 1.2 vs. 1.91 +/- 0.6; LTf(s) 3.6 +/- 1.4 vs. 2.6 +/- 0.7; SERV (mm) 7.5 +/- 4.8 vs. 18.5 +/- 6.6; Vr (mm) 4.4 +/- 2.1 vs. 13.5 +/- 5.3; ACT (m/s) 0.41 +/- 0.23 vs. 0.97 +/- 0.18.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226120 TI - Comparison of islet cell antibodies, islet cell surface antibodies and anti bovine serum albumin antibodies in type 1 diabetes. AB - The present study was undertaken to compare the changes in islet cell antibodies (ICA), islet cell surface antibodies using rat insulinoma cells (RINr-ICSA), and anti-bovine serum albumin antibodies (BSA-Ab) in the clinical course of type 1 (insulin-dependent) diabetes. Sera were obtained from 57 patients with type 1 diabetes and 47 normal controls. ICA, RINr-ICSA and BSA-Ab were detected by an enzymatic immunohistochemical method, an indirect immunofluorescence method and an enzyme-linked immunosorbent assay, respectively. The incidence of ICA significantly decreased with the duration of diabetes: less than 1 year: 5/6 (83%); 1-2 years: 3/6 (50%); 2-3 years; 2/6 (33%); greater than 3 years 6/39 (15%). There was a significant positive correlation between RINr-ICSA and BSA-Ab (P less than 0.05). These findings suggest that RINr-ICSA or BSA-Ab may be produced by some similar immune mechanism which is, however, different from ICA, and that they have no direct relation to the clinical course of diabetes. PMID- 2226121 TI - Islet cell antibodies are not specifically associated with insulin-dependent diabetes in Tanzanian Africans. AB - The prevalence of islet cell antibodies (ICA and CF-ICA) together with other organ-specific auto-antibodies was investigated in 122 newly presenting black Tanzanian diabetic patients in Dar es Salaam. ICA were found in three (8.6%) IDDM patients and five (6.8%) insulin-requiring NIDDM patients; six of the eight were also CF-ICA positive. Altogether 22% of patients showed one or more positive autoantibody result but there was no clustering of response, and no association of ICA with other antibodies except for two NIDDM subjects who showed one other positive result. There were no differences between insulin-requiring (IDDM) and NIDDM subjects or between younger (less than 30 years) and older patients. We conclude that there is no major association between diabetes and islet cell antibodies in black Tanzanians. PMID- 2226122 TI - Effect of acute hyperglycemia on plasma triglyceride concentration and triglyceride secretion rate in non-fasted rats. AB - The effect of an intravenous infusion of glucose on plasma triglyceride (TG) concentration in fed rats was determined in order to partially elucidate the mechanism of diabetes-induced hypertriglyceridemia. Glucose infused at 8 mg/kg per min caused the plasma TG concentration to be elevated significantly when compared to controls infused with saline alone. In rats which were euglycemic (clamped, insulin infused at 2.5 mU/kg per min), plasma TG concentration remained constant throughout the glucose infusion period (8 mg/kg per min). Hyperglycemic rats infused with insulin (2.5 mU/kg per min) as well as with glucose (16 mg/kg per min) were also hypertriglyceridemic. Infusion of insulin alone did not change the concentration of plasma TG over a 150 min period. Glucose was also infused (8 mg/kg per min) with somatostatin (1 micrograms/kg per min) to block endogenous production of insulin. Somatostatin infusion did not suppress glucose-induced hypertriglyceridemia. For all treatments, the net change in TG concentration was found to positively correlate with the net change in plasma glucose concentration at 150 min after the infusions (r = 0.83, P less than 0.001). The higher TG concentration in the glucose infused, hyperglycemic clamp and glucose plus somatostatin groups reflected an increased rate of TG secretion, in the presence of a lower concentration of plasma free fatty acids. These results suggest that in a non-fasted state, acute hyperglycemia increases plasma TG by stimulating hepatic TG secretion, in a manner which is independent of either plasma insulin or free fatty acids levels. PMID- 2226123 TI - Abnormalities of ascorbic acid metabolism and diabetic control: differences between diabetic patients and diabetic rats. AB - Ascorbic acid is required in the synthesis of collagen and is also an important anti-oxidant. In a previous study, plasma ascorbic acid concentration was found to be decreased in diabetic patients but there was no relationship with blood glucose level. In the current study of diabetic patients, both plasma ascorbic acid and its urinary excretion correlated inversely with glycosylated hemoglobin level. Plasma ascorbic acid was also lower in diabetic rats but urinary ascorbic acid was elevated. The divergent trend in urinary ascorbic acid excretion observed in diabetic patients and diabetic rats may be due to difference in the ability of these two species to synthesize ascorbic acid. Difference in renal reabsorption of ascorbic acid may also be a relevant factor. The lower plasma and urinary ascorbic acid levels in diabetic patients with more severe hyperglycaemia indicates that this group of patients is particularly at risk of developing deficiency of this vitamin. As ascorbic acid has many important functions in the body, it may be necessary to supplement this vitamin in patients with chronically poorly controlled diabetes. PMID- 2226124 TI - Beta-endorphin levels of children in acute stress. AB - In this study aiming to clarify the relationships between beta-endorphin and glucose levels, beta-endorphin levels were determined in children in acute stress. The study was carried out on 32 critically ill children between 5 days and 12 years presenting with clinical symptoms of acute infectious conditions. 11 healthy children were taken as controls. The results showed that although beta endorphin levels were elevated in all critically ill patients, these levels were significantly higher than control values in hyperglycaemic cases. The insulin levels were also elevated. A follow-up of nine of the hyperglycaemic cases showed a significant decline in beta-endorphin and insulin levels with recovery. Glucose tolerance was also normal. These results confirm the reports of many other studies on the role of beta-endorphin as a stress hormone. PMID- 2226125 TI - Human insulin dosage and distribution at the onset of type 1 diabetes mellitus. AB - The total insulin dosage and its distribution throughout the day were evaluated in newly diagnosed Spanish IDDM patients treated with semisynthetic human insulin. We assessed the insulin dosage and its distribution modifications related to an inpatient versus outpatient setting. We compared our results with classical theoretical algorithms based on patients treated with animal insulin and with alimentary habits which differ from our geographical area. The initial total daily dose (0.68 +/- 0.27 U/kg per day) did not substantially differ from the usual recommended dose (0.70-0.80 U/kg per day). A substantial decrease in total insulin dose was observed in ambulatory patients (0.55 U/kg per day). The reduction in dosage when we substituted regular insulin for intermediate acting insulin was smaller than what is commonly advised. A very low proportion of patients needed to add extra regular insulin to the pre-dinner intermediate insulin dose to achieve acceptable glucose control. Moreover, in these cases regular insulin comprised only 10% of total daily dosage, a proportion clearly inferior to that recommended. The majority of this group of patients needing regular insulin plus intermediate insulin at pre-dinner were treated with human zinc insulin. Most of our patients were acceptably controlled with a regular insulin dose before breakfast and lunch and an intermediate dose before dinner. Finally, human insulin pharmacokinetics plus our Mediterranean alimentary habits might be the explanation to our findings. PMID- 2226126 TI - In vivo metabolic activity of des-(B26-B30)-insulin-B25-amide and related analogues in the rat. AB - Metabolic potency of des-(B26-B30)-insulin-B25-amide, [TyrB25]des- (B26-B30) insulin-B25-amide and [HisB25]des-(B26-B30)-insulin-B25-amide was studied in anaesthetized rats. Compared to insulin, full potency for des-(B26-B30)-insulin B25-amide and an enhanced potency for both substituted analogues has been described previously on rat adipocytes in vitro. Hypoglycaemic effects following i.v. injection of all of these analogues were almost identical to those of native insulin with a half-maximal effective dose of approximately 3 nmol.kg-1. Stimulation of glucose metabolism during euglycaemic hyperinsulin-/analogueaemic clamp studies was indistinguishable from that of the native hormone with a maximal stimulation of approximately 19 mg.kg-1.min-1 and half-maximal effective hormone concentrations of approximately 1 pmol.ml-1. Analogue action on individual peripheral tissues estimated by the uptake of 2-deoxyglucose as well as stimulation of lipogenesis in epididymal fat was not different to that of insulin. These data demonstrate that C-terminal amidation of des-(B26-B30) insulin results in a shortened molecule with full in vivo metabolic potency. When substituting phenylalanine in position B25 by tyrosine or histidine, the insulin identical potency is preserved. PMID- 2226127 TI - The influence of dietary education in diabetic children. AB - The aim of our study was to evaluate the efficacy of dietary education in inducing modification of the diet and to measure biochemical parameters in 36 children and adolescents with IDDM. At the beginning of the study, each patient was evaluated as follows: food intake (by the method of the 24-h recall for 3 days), auxological parameters, biochemical parameters. Thereafter a program of nutritional guidelines was provided. Subsequent meetings took place at 1-month intervals. The study ended 3 months later, when all the parameters were completely revalued. We observed improved nutrition in our patients both in terms of total caloric intake and calorie distribution. In particular there was an increase in carbohydrates and a reduction in lipids, reaching the percentage levels recently recommended. With a reduction in lipid intake a significant decrease in LDL cholesterol and a significant increase in HDL cholesterol were noticed in our patients. These modifications are very important for the prevention of arteriosclerosis and thus macrovascular disease. We maintain that dietary education plays an important role in helping children and adolescents with IDDM to follow a suitable diet. PMID- 2226129 TI - [Regeneration of the skeletal muscle of young and old rats after total cross cutting]. PMID- 2226128 TI - Effects of glucose and insulin on cultured human microvascular endothelial cells. AB - The prolonged effects of glucose and insulin on cultured human microvascular endothelial cells from omental tissue (HOMEC) were observed to identify the contribution of sustained hyperglycemia and/or hyperinsulinemia to the pathogenesis of diabetic microangiopathy. When the cells were cultured for 10 days in Medium 199 with 100 or 500 mg/dl glucose, the number of cells was reduced to 78% in the culture of 500 mg/dl glucose as opposed to that of 100 mg/dl glucose. The difference in the number of cells between these two groups became obvious between the 5th and the 7th culture days. The replacement of D-glucose with L-glucose did not show any reduction in the number of cells, indicating the impertinence of high osmolarity, induced by high glucose (305 mOsm/kg) to the number of cells. This reduction resulted from the cellular damage during the culture period rather than the retardation of growth, according to the experiments of [3H]thymidine uptake and the 51Cr release assay. Since the uptake of glucose, measured as the uptake of 3-O-methyl-alpha-D-glucose, was higher and the Na+/K+ pump activity decreased in high glucose condition, it is suggested that the excessive intracellular accumulation of glucose caused the damage of cells through the disturbance of ion exchange. Insulin augmented the reduction in the number of cells induced by high glucose when supplemented together for 10 days at concentrations of 10(-6)-10(-12)M. The uptake of glucose increased further to 154% by the addition of insulin to high glucose as compared to that of high glucose alone, however, the decreased Na+/K+ pump activity by high glucose was restored to the control level by insulin. The aggravating effect of insulin to the cellular damage induced by high glucose seems to be mediation via the mechanism other than the decreased Na+/K+ pump activity. In conclusion, HOMEC were gradually damaged by high glucose and by insulin, and hyperglycemia and hyperinsulinemia would be of pathogenetic importance for diabetic microangiopathy. PMID- 2226130 TI - [Cloning and primary sequence of the gene coding for major heat shock protein (HSP70) in the silkworm]. PMID- 2226131 TI - [UV-photolysis of amino acids and peptides. Cleavage of peptide bond during laser irradiation]. PMID- 2226133 TI - [The effect of elevated functional load on the activation of satellite cells in skeletal muscles of adult rats]. PMID- 2226132 TI - [Immunogenicity and protective activity of water-soluble polymer-metal complexes of protein antigens]. PMID- 2226134 TI - [A drop in oxygen tension along the capillary in skeletal muscle: experimental study]. PMID- 2226135 TI - [Phenomenon of non-random large-scale fragmentation of DNA in cell nuclei]. PMID- 2226136 TI - [The mechanism of potentiating effect of glutamate on gastric secretion]. PMID- 2226137 TI - [Latent excitation after termination of long-term potentiation in the hippocampus]. PMID- 2226138 TI - [Organization of transcriptionally inactive regions of interphase chromosomes]. PMID- 2226139 TI - [A fragment of human DNA lacking hybridization with chimpanzee DNA]. PMID- 2226140 TI - [ATP synthesis in mitochondria: interaction of redox-chains in outer and inner membranes]. PMID- 2226141 TI - [C-terminal polyarginine tract of hepatitis B core antigen is located on the outer capsid surface]. PMID- 2226142 TI - [Metabolism of phosphorus-containing compounds in the liver of the ground squirrel (Citellus undulatus) during various physiological states]. PMID- 2226143 TI - [Phorbol ester (TPA) modulation of the responses of the snail neuronal membrane to the rapid application of acetylcholine]. PMID- 2226144 TI - [Changes in the respiration and intracellular pH in a cell culture under the action of oligomycin]. PMID- 2226145 TI - [Inhibition of the reproduction of the human immunodeficiency virus in a cell culture with antisense oligonucleotide derivatives]. PMID- 2226146 TI - [A new positively charged nonhistone protein participates in the condensation of inactive chromatin at the terminal stage of the differentiation of chick erythrocytes]. PMID- 2226147 TI - [The effect of unilateral homotopic neural transplantation on the recovery of the motor function of the hindlimbs in rats with bilateral removal of the sensorimotor area of the cortex]. PMID- 2226148 TI - [The role of rhythmic activity in the processes of information fixation and reproduction in a model network made up of nerve-like elements]. PMID- 2226149 TI - [Discrete levels of cell activation]. PMID- 2226150 TI - [The specialized contact of an astrocyte containing a vesicle aggregation with the dendritic spine in the cerebral cortex of the cat]. PMID- 2226151 TI - [The formation of specific sebaceous skin glands in the early postnatal ontogeny]. PMID- 2226152 TI - [The retransplantation of embryonic nerve tissue into the mammalian brain]. PMID- 2226153 TI - [The differential expression of crystallins and concanavalin A-binding proteins in different cellular "compartments" of the amphibian crystalline lens]. PMID- 2226154 TI - [The characteristics of the progeny of irradiated males from 2 lines of Drosophila virilis differing by the level of genetic instability]. PMID- 2226155 TI - [Lessons from reoperations in 55 patients with primary hyperparathyroidism]. AB - On the basis of 70 re-operations in 55 patients (34 women, 21 men, median age 58 [43-83] years) suffering from primary hyperparathyroidism the reasons for failure of the first operations were analysed. The main reasons were inadequate exploration of the neck (failure to identify all four glands), failure to recognize multiple gland involvement, or inadequate resection in cases where more than one gland was affected. An abnormally situated gland was a less common cause, as shown by the fact that 41 out of the 73 glands removed at the last re operation were situated in the normal position or in its immediate vicinity; in 20 cases the surgeon had failed to recognise multiple gland disease. Next in order of importance were anatomical variations in the location (32 out of 73 tumours) or the number of the glands (9 patients with hyperplasia of 5 glands). At the re-operations 89% of the parathyroid tumours were found in the neck region or would have been accessible from the neck at the time of the first operation. Overall, the hypercalcaemia was permanently rectified in 96.6% of the patients. During the last 10 years 94% of patients have been normocalcaemic postoperatively, thanks mainly to the re-implantation of autologous parathyroid tissue, preserved by low-temperature storage. The incidence of permanent unilateral recurrent nerve paresis attributable to the re-operations was 6%. PMID- 2226156 TI - [Paroxysmal non-hereditary angioedema]. AB - Recurrent hypovolaemic shock had been occurring over the last five and four years, respectively, in a 53-year-old woman and a 46-year-old man who had previously been healthy. The attacks were characterized by a tension feeling and sometimes oedema in the limbs, as well as increased thirst. Within a few hours sweating, tachycardia, orthostatic complaints and shock would occur. The woman's systolic blood pressure would fall to 70 mm Hg and the pulse rate rise to 150/min. The man's blood pressure was not measurable by sphygmomanometer during his first attack. Haematocrit rose to 61 and 71.5%, haemoglobin concentration to 20.7 and 21.3 g/dl, respectively. On administration of plasma expanders all abnormal clinical and biochemical changes quickly disappeared, only to recur within weeks or months. The cause of the condition is an increased permeability of the tissue capillaries, while renal, pulmonary and cerebral vessels apparently are unaffected. During ketotifen and tebonin (gingko biloba extract) administration to the man, he required no further hospitalization for nine months, after which he had three severe attacks. The woman had a severe attack of hypovolaemic shock one month on this treatment. The prognosis of capillary leak syndrome is bad. PMID- 2226157 TI - [Atypical joint symptoms as initial symptoms of varicella infection in chronic myeloid leukemia]. AB - A 25-year-old man, known to have chronic myeloid leukaemia for four years, acutely developed a fever of 39.5 degrees and severe pain in the shoulder and hip joints. There was no evidence of joint disease. Treatment with indomethacin briefly improved the symptoms, but within 72 hours the patient developed a fulminant illness with high fever and clinical as well as biochemical signs of a severe consumption coagulopathy. Herpetiform efflorescences appeared over the head and trunk shortly before death. At autopsy there was histological and immunohistochemical evidence of a varicella infection with hepatitis, oesophageal involvement and severe internal organ bleedings. In immune-compromised patients with atypical prodromal symptoms a varicella infection must be considered so that causal treatment with acyclovir and hyperimmune-globulin can be begun in time. PMID- 2226158 TI - [Acute emphysematous cholecystitis as a cause of pneumoperitoneum]. AB - A 48-year-old man developed progressively more severe epigastric pain, pain on pressure in the right upper abdomen and fever up to 38.6 degrees C so that acute cholecystitis was suspected. Ultrasound did not demonstrate a gall-bladder but a sickle shaped, dense echo with a distal adjoining echo-free zone. Computed tomography revealed air in the gall-bladder lumen as well as intramural and pericholecystic air pockets, findings pathognomonic for emphysematous cholecystitis. In addition pneumoperitoneum was diagnosed. Subsequent cholecystectomy intraoperatively revealed a gangrenous, nonperforating gall bladder in which E. coli was demonstrated. During the first postoperative week, there were no complications under transitory antibiotic treatment with tobramycin and ticarcillin with clavulanic acid. Then, an abscess developed in the residual gall bladder bed; this abscess was cured after drainage, local irrigation and re initiation of antibiotic treatment. The patient was finally discharged well. PMID- 2226159 TI - [Extracorporeal shockwave lithotripsy: what system and for what purpose?]. PMID- 2226160 TI - [Therapy of sickle cell crisis]. PMID- 2226161 TI - [Autotransplantation of splenic tissue]. PMID- 2226162 TI - [Balloon catheter recanalization and local thrombolysis in pulmonary embolism]. PMID- 2226164 TI - [Cardiac pacemaker implantation in unrecognized obstructive sleep apnea syndrome]. AB - A cardiac pacemaker was implanted because of nocturnal sinus arrhythmia into a 53 year-old man with hypersomnia. After other patients had reported loud snoring and breathing pauses, which appeared to be dangerously long, polysomnography was performed. It indicated a marked obstructive sleep apnoea syndrome with an apnoea index of 55 and an average apnoea duration of 35 seconds. The nocturnal cardiac arrhythmias disappeared under continuous nasal raised pressure ventilation. PMID- 2226163 TI - [Pneumocystis carinii pneumonia in HIV infection: better prognosis because of early diagnosis]. AB - The clinical presentation of 60 consecutive Pneumocystis carinii pneumonias in 58 HIV-infected patients (48 men, 10 women, mean age 34 [22-53] years) was prospectively evaluated from April to August 1989 and compared with 60 consecutive P. carinii pneumonias in 59 HIV-infected patients (55 men, 4 women, mean age 37.5 [22-60] years) between 1981-88. Mortality rates within 14 days after diagnosis of P. carinii pneumonia were 50% (8 of 16 patients) until 1985, 20.5% (9 of 44) between 1986 and August 1988, and 1.7% (one of 60) in 1989. The degree of severity of the pneumonias at time of diagnosis was markedly lower in 1989, as shown by following parameters (averages of 1989, compared with averages of 1981-88): lactate dehydrogenase 540 (250-1419) U/l versus 680 (235-1920) U/l (not significant); alveolo-arterial difference of partial oxygen tension (pA-aO2) 22.9 (0.5-73.5) mmHg versus 39.7 (19-70) mmHg (P less than 0.001); score of radiological findings 1.4 (0-3) versus 2.7 (0-4) (P less than 0.001). In 1989, mainly clinical symptoms (dry cough: 57 of 60 cases, dyspnea: 44 of 60 cases, fever: 43 of 60 cases) initiated the diagnostic procedure: chest radiographs, lactate dehydrogenase and pA-aO2 were normal in 13, 25 and 33 episodes, respectively. The lower mortality rate of P. carinii pneumonia could not primarily be explained by therapeutical progress since the treatment of choice did not change fundamentally since 1981. Above all, early diagnosis fundamentally determined the probability of survival. PMID- 2226165 TI - [Misdiagnosis of psychic symptoms of hyperthyroidism in affective psychosis]. AB - A 71-year-old woman known to have suffered from a depressive illness for fifty years developed further psychological and somatic symptoms 18 months ago (agitation, increased impulsiveness, depressive mood, decreased appetite, diarrhoea and weight loss). Within five days there occurred nocturnal confusion with disordered word finding and counting. Biochemical tests indicated hyperthyroidism and scintigraphy showed multifocal activity increase. The psychological and somatic symptoms responded to thyrostatic treatment with carbimazole, 30 mg daily. This case demonstrates that added somatic causes of psychological symptoms should be thought of in previously known psychiatric illness. PMID- 2226166 TI - [Diagnosis of Barrett esophagus]. PMID- 2226167 TI - [Therapy of Barrett esophagus]. PMID- 2226168 TI - [Pathogenesis and therapy of listeriosis]. PMID- 2226169 TI - [Glycosylated hemoglobin or fructosamine: what must one measure?]. PMID- 2226170 TI - [Transfer factor]. PMID- 2226171 TI - [Hydrostatic pressure in esophageal varices and the risk of an esophageal variceal hemorrhage]. PMID- 2226172 TI - [Modern methods for the regulation of type 1 diabetes?]. PMID- 2226173 TI - [Proglottids of Taenia solium]. PMID- 2226174 TI - [Crohn's disease: disease activity and recurrence following surgery]. AB - The data from 238 patients (108 men, 130 women, mean age 29 [15-71] years), who had undergone operations for Crohn's disease between 1968 and 1988, were analysed retrospectively with the purpose of ascertaining the significance of an endoscopically demonstrated "early recurrence". In 170 patients postoperative colonoscopy had been performed at least once. In 130 patients the activity of the disease in the years before and after operation was compared in terms of such parameters as haemoglobin, erythrocyte sedimentation rate, serum albumin, body weight and the frequency of acute flare-ups of the disease and admissions to hospital. The probability of an endoscopically demonstrable recurrence was 90% after 5 years, while the corresponding figure for a symptomatic recurrence was 40%. This indicates that the routine performance of postoperative colonoscopies is of no value in assessing the prognosis. The probability of a reoperation was 21% after 5 years; in cases where both the ileum and colon were involved the probability was three times as high as in those with isolated involvement of either the small or the large intestine. Post-operatively, a substantial reduction in disease activity of several years' duration was achieved in the overall majority of cases. PMID- 2226175 TI - [The implantation of hip joint endoprostheses: with or without cement?]. PMID- 2226176 TI - [The duties of the employer in continuing medical education. The judgement of the Federal Labor Court of 22 February 1990]. PMID- 2226177 TI - [Coffee and serum cholesterol]. PMID- 2226178 TI - [The nephrotoxic effect of therapy with fumaric acid esters in psoriasis]. AB - Two sisters, aged 25 and 29 years, with generalized psoriasis guttata since childhood, developed nausea, upper-abdominal pain, loss of appetite, palpitations and flushes in the course of local and oral administration of fumaric acid esters. Because of these side effects the treatment was discontinued after about two weeks, and the symptoms disappeared. But proteinuria and haematuria were subsequently noted, creatinine concentration rose to 2.2 and 2.5 mg/dl, respectively, while creatinine clearance fell to 44 and 27 ml/min, respectively. Examination of urinary sediments and analysis of urinary proteins gave results compatible with tubular-interstitial renal damage. The abnormal renal functions and urinary findings proved reversible within three weeks. PMID- 2226179 TI - [Extraintestinal strongyloidiasis in the acquired immunodeficiency syndrome]. AB - A 41-year old man of Brazilian origin, suffering from AIDS for one year, fell ill with pyrexia of over 39 degrees C, dyspnoea, chest pain and deterioration in his general condition. At the same time he noted a discrete skin eruption, mainly on the upper limbs. Diarrhoea began later. A chest radiograph revealed bilateral infiltrates. The blood showed leucocytosis (11,000/microliters) with pronounced increase of eosinophil granulocytes (47.5%). Alkaline phosphatase was raised to 170 U/l. Suspicion of strongyloidiasis was confirmed by the discovery of numerous Strongyloides stercoralis larvae in the faeces. A few days after starting treatment with mebendazole, 400 mg daily, he felt better and the diarrhoea stopped. However, as the lung infiltrates remained unchanged and hilar lymph node enlargement now appeared, the dose of mebendazole was raised to 2500 mg daily. The abnormal findings then cleared up: Strongyloides stercoralis larvae ceased to be demonstrable and the patient gained 10 kg in weight. PMID- 2226180 TI - [The differential diagnosis of Alzheimer's dementia from the neurological viewpoint]. PMID- 2226181 TI - [The "tuberculin intoxication" of 1890]. PMID- 2226182 TI - [Gout without hyperuricemia?]. PMID- 2226183 TI - [Pacemaker aftercare: malfunction in magnetic exposure]. PMID- 2226184 TI - [The growth hormone as a geriatric agent?]. PMID- 2226185 TI - [Epidemiology of hypercalcemia. Significance of the determination of intact parathyroid hormone for differential diagnosis]. AB - Serum-calcium levels were determined in 9666 hospital inpatients during one year. Hypercalcaemia was present in 101 patients (51 women, 50 men, mean age 57 years). In 46 patients, hypercalcaemia was caused by malignancy. The second commonest cause was primary hyperparathyroidism (pHPT) in 35 cases. In the other 20 patients, hypercalcaemia was related to thiazid medication (8 patients), elevated 25-hydroxy-vitamin-D3-levels (six patients) or immobilisation (two patients). In four patients, no cause was found. Intact parathyroid hormone levels reliably distinguished patients with pHPT (values greater than 60 ng/l) from patients with hypercalcaemia of other causes (values less than 40 ng/l). Other laboratory tests were less useful. Serum-calcium levels greater than 2.9 mmol/l were found only in pHPT and hypercalcaemia of malignancy. In pHPT, the medical history frequently revealed nephrolithiasis (12 patients) and gastrointestinal ulcers (8 patients), whereas weight loss was far more common in hypercalcaemia of malignancy (28 patients). PMID- 2226186 TI - [Penile plication for the treatment of severe penile deviations]. AB - Penile plication procedure was performed on 27 patients (median age 24 years) to correct marked penile deviation (mean deviation angle 50 degrees). On average 4 (2-10) sutures were necessary. Normal intercourse and potency was restored in all. 26 patients were fully satisfied with the result, while in three there were suture problems (fistula, granuloma). There was one recurrence, three weeks postoperatively, in a patient who failed to follow the recommended six-week period of sexual abstinence. But this recurrence was lastingly corrected by a second penile plication procedure. No lasting complications were noted a mean of 48 months postoperatively. This type of operation is the treatment of choice for significant penile curvature. PMID- 2226187 TI - [Acute segmental hemorrhagic penicillin-associated colitis]. AB - Four days after beginning a perioperative antibiotic prophylaxis with amoxicillin and clavulanic acid a 33-year-old patient developed an acute haemorrhagic diarrhoea with cramp-like lower abdominal pain. Coloscopy revealed diffuse mucosal oedema with map-like ulcerations, increased susceptibility to trauma and submucous haemorrhages extending from the middle of the ascending to the middle of the descending colon. Granulocytic inflammation with cryptal atrophy was seen histologically. Stool cultures, including tests for Clostridium difficile toxin, were normal. All symptoms disappeared within three days of discontinuing the medication. Coloscopy after one week revealed marked improvement, after three months nothing abnormal. Acute segmental haemorrhagic penicillin-associated colitis is rare and must be distinguished from antibiotic-associated pseudomembranous colitis. PMID- 2226188 TI - [Floating right atrial thrombus as the cause of recurring pulmonary embolisms]. AB - After an attack of pleuropneumonia a 25-year-old woman developed persistent dyspnoea due to pulmonary emboli, as demonstrated by scintigraphy. There was no clinical or phlebographic evidence of the peripheral venous system as the source. Two-dimensional echocardiography demonstrated a floating spherical tumour in the right atrium, attached to the interatrial septum and prolapsing into the right ventricle during ventricular diastole. Because of the risk of further thromboembolic episodes the tumour was removed operatively without any complication. It proved to be myxoma-like, 3 x 3 cm in diameter. Histologically it was a thrombus without evidence of myxoma. No further thromboemboli occurred under phenprocoumon anticoagulation. PMID- 2226189 TI - [Diagnosis and therapy of adrenal cortex insufficiency]. PMID- 2226191 TI - [Early detection of type I diabetes]. PMID- 2226190 TI - [Amylin, islet amyloid and diabetes mellitus type II]. PMID- 2226192 TI - [Long-term success of coronary angioplasty after repeated treatment]. AB - To ascertain the long-term results after second and third angioplasties for coronary stenosis the coronary angiograms from 1504 consecutive patients with coronary heart disease (1211 men, 293 women, mean age 57 [27-82] years) were retrospectively surveyed. A good initial response (at least 20% reduction in stenosis) was achieved in 295 out of 306 second angioplasties (95.5%), and in all 36 third angioplasties. Viewed overall, these results are significantly better (P less than 0.005) than those achieved at the initial angioplasty (1386 out of 1504 patients; 92.2%). The reduction in the severity of the stenosis achieved at the second angioplasty (from 86 to 24%) and at the third angioplasty (from 86 to 26%) was the same as at the first angioplasty (from 88 to 28%). Serious complications after the first angioplasty were infrequent (death in 0.2%, emergency bypass in 0.4%, myocardial infarction in 0.5%), and no complications were noted after second and third angioplasties. A good long-term outcome (at least 20% reduction in stenosis at 3-4 months) was slightly more frequent after the second and third angioplasties (103 out of 170 [60.6%] and 14 out of 17 patients, respectively) than after the first intervention (532 out of 926 patients; 57.5%). In keeping with these results, the degree of stenosis found at follow-up angiography was significantly lower (first intervention 54.8%, second intervention 50.3%, third intervention 36.9%). There were only 57 patients (3.8%) who ultimately required operative treatment. These figures indicate that the probability of a good long term outcome from coronary angioplasty increases each time the stretching operation is repeated. Only a very small proportion of patients will require bypass surgery. PMID- 2226193 TI - [Results of therapy in Hodgkin's disease]. AB - The results of therapy in 239 patients (161 men, 78 women, median age 33 [13-80] years) who had been treated for Hodgkin's disease between 1972 and 1986 were evaluated retrospectively. The proportion of complete remissions depended on the stage of the disease and was 90% (35 out of 39 patients) for stage IA, 90% (9 out of 10) for stage IB, 84% (40 out of 48) for stage IIA, 88% (22 out of 25) for stage IIB and 86% (37 out of 43) for stage IIIA. At five and ten years, survival rates among patients in stages IA to IIB were 76 and 69%, respectively, and for patients in stage IIIA 81 and 52%, respectively. For patients who enjoyed complete remissions the probability of surviving for 5 or 10 years without recurrence was 62% or 54%, respectively, for stages IA to IIB, and 75 or 43%, respectively, for stage IIIA. There were no statistically significant differences between stages I, II and IIIA as regards remission rate, survival time or recurrence-free survival time. During these stages the patient's age proved to be the only prognostic factor of any statistical significance. For stages IIIB and for IVA and IVB the proportion of complete remissions achieved by combined chemotherapy with COPP was 62%. At 5 and 10 years the proportion of these patients in permanent remission was 63 and 53%, respectively, while survival rates in the entire series were 46% and 40%, respectively. A genuine cure--in the sense of at least 10 years' survival without recurrence after the first complete remission--can be expected in one third of patients in stages IIIB to IVB. PMID- 2226194 TI - [Computed tomographic detection of liver hemangiomas]. AB - A 67-year old woman had noticed increasing growth of hair on the face and extremities for eight months. The testosterone level was raised at 2.6 micrograms/l and 24-hour urinary cortisol excretion was 160 micrograms. Ultrasound scanning showed a tumour measuring 14 x 10 x 10 cm in the left suprarenal, as well as several irregular space-occupying lesions in the liver, some of which were echo-rich. By computed tomography these structures were hypodense and did not concentrate any contrast medium. A provisional diagnosis of suprarenal carcinoma with hepatic metastases was accordingly made. After surgical removal of the suprarenal carcinoma the hormonal parameters unexpectedly returned to normal. Repetition of the computed tomography failed to elucidate the nature of the liver lesions. However, superselective hepatic angiography revealed the typical picture of haemangiomas of the liver. The existing computed tomograms were therefore reviewed. The diagnostic error was found to be due to incorrect timing of the interval between injection of contrast medium and performance of computed tomography. PMID- 2226195 TI - [Therapy of tuberculosis]. PMID- 2226196 TI - ["Functional" gastrointestinal pain]. PMID- 2226197 TI - [Fatal lung embolism during ultrahigh-dose streptokinase treatment]. PMID- 2226198 TI - A widely distributed antigen developmentally regulated in the nervous system. AB - We have identified a glycoprotein (BEN) of 95-100 x 10(3) Mr using a monoclonal antibody. This protein is transiently expressed at the cell surface of the peripherally projecting neurons, i.e. motoneurons of the spinal cord and cranial nuclei, sensory neurons of the dorsal root and cranial sensory ganglia and sympathetic, parasympathetic and enteric neurons. In vitro cultures of dorsal root and sympathetic ganglia have shown that BEN is expressed on neurons but not on glial cells. On motor and sensory neurons, BEN first appears at the level of the cell body just after withdrawal from the cell cycle. Soon afterwards, expression of the antigen extends to the elongating axon. After a few days, BEN is no longer expressed by the motor and sensory neurons, disappearing first from the cell body and then progressively from the fibres. The loss of expression is concomitant with the onset of intense proliferation of satellite and Schwann cells. This modulated expression within the nervous system is unlike that of any surface glycoprotein so far described in vertebrates. Preliminary biochemical analysis indicates that, although it bears the adhesion-associated epitope HNK-1, BEN does not share characteristics with any previously described axonal glycoprotein. Consequently, we speculate that this glycoprotein might be a novel molecule implicated in selective adhesion phenomena, such as axonal fasciculation. PMID- 2226199 TI - The induction of anterior and posterior neural genes in Xenopus laevis. AB - We have investigated the interactions between mesoderm and ectoderm that result in the formation of a regionally differentiated nervous system in Xenopus embryos. We have used genes expressed at different positions along the neural tube as regional markers of neural induction in both whole, and in experimentally manipulated embryos. By comparing transcription from the anterior marker, XIF3, with that from the posterior marker, X1Hbox6, and the general neural marker XIF6, we have shown that the normal induction process requires interactions between ectoderm and mesoderm that persist through gastrulation into the late neurula stages. We have found that competence of the ectoderm to respond to induction is lost at the same early neurula stage for all three marker genes. Using rhodamine dextran-labelled mesoderm, we have established that the duration of contact between ectoderm and mesoderm required for gene activation in conjugates is the same for each of the markers. We have, however, identified regions of the mesoderm that can induce different combinations of neural marker gene expression. The anterior mesoderm induces expression of the anterior marker, XIF3, and the later migrating posterior mesoderm induces the ectoderm overlying it to express the posterior marker X1Hbox6. It has been proposed that neural inducing signals reach the ectoderm by two different routes: from mesoderm lying directly beneath the ectoderm or along the plane of the ectoderm. We have assessed the contribution of each route in respect of our three neural markers and find that a signal passing directly from mesoderm to ectoderm fully accounts for neural gene expression. We were unable to detect an inducing signal that passes along the plane of the ectoderm. PMID- 2226200 TI - Autonomous determination of anterior structures in the early Drosophila embryo by the bicoid morphogen. AB - A small number of maternal effect genes determine anterior-posterior pattern in the Drosophila embryo. Embryos from females mutant for the maternal gene bicoid lack head and thorax. bcd mRNA becomes localized to the anterior tip of the egg during oogenesis and is the source for the morphogen gradient of bcd protein. Here we show that in vitro transcribed bicoid mRNA that has its own leader sequences substituted by the Xenopus beta-globin 5' untranslated sequences is translated more efficiently than bicoid mRNA with the natural 5' mRNA leader when tested in vitro and in Drosophila Schneider cells. When injected into bicoid mutant embryos, only the bcd mRNA with the beta-globin leader sequence, substituted for the natural leader, is able to induce anterior development. We used P-transformation to show that sequences in the 5' leader are neither necessary for localization of the transcript nor for the translational block of the bcd mRNA during oogenesis. For our injection experiments, we used only one of the identified splicing forms of bcd mRNA. The bcd protein species derived from this mRNA is able to induce anterior development at any position along the anterior-posterior axis. Thus bicoid protein can induce development of head and thorax independent of any other specifically localized morphogenetic factor. Our findings further support the notion that the concentration gradient of bcd protein, and not the existence of different forms of bcd protein, is responsible for specifying subregions of the embryo. PMID- 2226201 TI - Single cell transplantation reveals interspecific cell communication in Drosophila chimeras. AB - Cell-cell communication is not only a common strategy for cell fate specification in vertebrates, but plays important roles in invertebrate development as well. We report here on experiments testing the compatibility of mechanisms specifying cell fate among six different Drosophila species. Following interspecific transplantation, the development of single ectodermal cells was traced in order to test their abilities to proliferate and differentiate in a heterologous environment. Despite considerable differences in cell size and length of cell cycle among some of the species, the transplants gave rise to fully differentiated clones that were integrated into the host tissue. Clones comprised cells of epidermal and/or neural histotypes, indicating that mechanisms mediating the epidermal/neural dichotomy in the ectoderm are conserved between the species. Cells of the neural lineages differentiated into neurones, glia, or both. Moreover, heterologous neurones sent out axons that followed major pathways along nerves and within the neuropile, demonstrating their ability to recognize positional cues in the heterologous CNS of the host. PMID- 2226202 TI - Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP-2A). AB - Bone morphogenetic protein-2A (BMP-2A) is a member of the transforming growth factor beta (TGF beta) gene family that has been implicated in cartilage and bone formation. Here we use in situ hybridization to show that BMP-2A RNA is expressed in a variety of embryonic epithelial and mesenchymal tissues outside of the developing skeletal system, including cell populations known to play important roles in morphogenesis. Thus, high levels of transcripts are found in developing limb buds (ventral ectoderm and apical ectodermal ridge), heart (myocardium of the atrioventricular canal), whisker follicles (ectodermal placodes, hair matrix and precortex cells), tooth buds (epithelial buds, dental papilla and odontoblasts), and craniofacial mesenchyme, as well as a number of other sites. The expression patterns of BMP-2A are different from those of TGF beta-1, -2 and 3, and this is illustrated in detail in the developing whisker follicles. These results suggest that BMP-2A plays multiple roles in morphogenesis and pattern formation in the vertebrate embryo. PMID- 2226203 TI - Localization of the DER/flb protein in embryos: implications on the faint little ball lethal phenotype. AB - Antibodies were raised against the Drosophila EGF receptor homolog (DER) and used for immunohistochemical analyses of Drosophila embryos. We found that DER is localized in a wide array of embryonic tissues, displaying a dynamic pattern of expression. DER appears to be expressed in all cells at the cellular blastoderm and gastrula stages. In extended-germ-band embryos, it is found predominantly in the mesoderm and the head. Finally, in retracted-germ-band embryos, DER immunoreactivity is most pronounced at sites of somatic muscle attachments and along the ventral midline of the CNS. We have thus observed that DER is expressed in the diverse tissues which are affected in the DER faint little ball (flb) embryonic lethal phenotype. The different pattern and extent of expression in each tissue suggests that the disparate aspects of the flb phenotype may result from different mechanisms of DER function. To understand the basis for the CNS phenotype of DER/flb mutants, we have closely followed the collapse of the CNS in mutant embryos. Our observations on the evolution of the final CNS phenotype, in combination with the temporo-spatial pattern of appearance of DER in the ventral neuroepithelium, suggest that this receptor participates in the second phase of neuron-glia interactions, namely in stabilization of the ladder-like CNS scaffolding formed by outgrowth of pioneer axonal processes along the glial pre pattern. PMID- 2226204 TI - The Notch locus of Drosophila is required in epidermal cells for epidermal development. AB - The Notch locus of Drosophila plays an important role in cell fate decisions within the neurogenic ectoderm, a role thought to involve interactions at the cell surface. We have assayed the requirement for Notch gene expression in epidermal cells by two kinds of genetic mosaics. First, with gynandromorphs, we removed the wild-type gene long before the critical developmental events to produce large mutant clones. The genotype of cells in large clones was scored by means of an antibody to the Notch protein. Second, using mitotic recombination, we removed the gene at successively later times after completion of the mitotically active early cleavage stages, to produce small clones. These clones were detected by means of a linked mutation of cuticle pattern, armadillo. The results of both experiments demonstrate a requirement for Notch expression by epidermal cells, and thus argue against the model that the Notch product acts as a signal required only in the neuroblast to influence neighboring epidermal cells. The mitotic recombination experiment revealed that Notch product is required by epidermal cells subsequent to neuroblast delamination. This result implies that the Notch gene functions to maintain the determined state of epidermal cells, possibly by mediating cell surface interactions within the epidermis. PMID- 2226205 TI - Identification of a novel growth factor with transforming activity secreted by individual chick embryos. AB - Previously we have developed a microassay for anchorage independent growth (AIG) of fibroblasts in soft agar, which can detect very small quantities of transforming growth factors (TGFs). Using this assay, we have shown that small pieces of dissected chick embryo tissue will stimulate AIG of both NR6 and NRK 49f cells, and that this property can be used to map production of growth factors with transforming activity in individual early embryos. We now show that this activity can be transferred to conditioned medium (CM) prepared using chick embryo tissue. Using two cell lines with differential responsiveness to TGFs, and by coincubating normal and heat-treated CM with trypsin, Con-A and neutralising antibodies, we show that CM contains at least two different growth factors with transforming activity. One of these is heat-stable, and stimulates colony formation in NRK 49f cells in the presence of EGF, but not in its absence. This activity corresponds to a TGF beta-like molecule. The other component is a heat labile glycoprotein, which has TGF alpha-like properties, but does not appear to behave like known TGFs with these properties. It therefore appears to be a novel growth factor. Both activities are present from the intermediate primitive streak stage of development. PMID- 2226206 TI - The effects of embryonic retinal neurons on neural crest cell differentiation into Schwann cells. AB - Amongst the many cell types that differentiate from migratory neural crest cells are the Schwann cells of the peripheral nervous system. While it has been demonstrated that Schwann cells will not fully differentiate unless in contact with neurons, the factors that cause neural crest cells to enter the differentiative pathway that leads to Schwann cells are unknown. In a previous paper (Development 105: 251, 1989), we have demonstrated that a proportion of morphologically undifferentiated neural crest cells express the Schwann cell markers 217c and NGF receptor, and later, as they acquire the bipolar morphology typical of Schwann cells in culture, express S-100 and laminin. In the present study, we have grown axons from embryonic retina on neural crest cultures to see whether this has an effect on the differentiation of neural crest cells into Schwann cells. After 4 to 6 days of co-culture, many more cells had acquired bipolar morphology and S-100 staining than in controls with no retinal explant, and most of these cells were within 200 microns of an axon, though not necessarily in contact with axons. However, the number of cells expressing the earliest Schwann cell markers 217c and NGF receptor was not affected by the presence of axons. We conclude that axons produce a factor, which is probably diffusible, and which makes immature Schwann cells differentiate. The factor does not, however, influence the entry of neural crest cells into the earliest stages of the Schwann cell differentiative pathway. PMID- 2226207 TI - Interaction between satellite cells and skeletal muscle fibers. AB - Single myofibers with attached satellite cells isolated from adult rats were used to study the influence of the mature myofiber on the proliferation of satellite cells. The satellite cells remain quiescent when cultured in serum containing medium but proliferate when exposed to mitogen from an extract of crushed adult muscle. The response of satellite cells to mitogen was measured under three situations with respect to cell contact: (1) in contact with a viable myofiber and its basal lamina, (2) detached from the myofiber by centrifugal force and deposited on the substratum and (3) beneath the basal lamina of a Marcaine killed myofiber. The results show that satellite cells in contact with the plasmalemma of a viable myofiber have reduced mitogenic response. Since inhibiting growth may induce differentiation, I tested whether satellite cells proliferating on the surface of a myofiber would fuse. Although the satellite cell progeny were fusion competent, they did not fuse with the myofiber. To determine whether fusion competence of the myofiber changes with time in culture, embryonic myoblasts were challenged to fuse with myofibers that had been stripped of satellite cells and cultured for several days. The myoblasts fused with pseudopodial sprouts growing from the ends of the myofiber, but did not fuse with the original myofiber surface. These results indicate that contact with the surface of a mature myofiber suppresses proliferation of myogenic cells but the cells do not fuse with the myofiber. PMID- 2226208 TI - Differentiation of tropomyosin-containing myofibrils in cleavage-arrested ascidian zygotes expressing acetylcholinesterase. AB - Two muscle differentiation programs, acetylcholinesterase and tropomyosin containing filaments and fibrils, occur together in the same cleavage-arrested zygotes (1-celled) of the ascidian Ciona intestinalis. Coexpression in such undivided but developing 'embryos' is consistent with the idea that separate elements of muscle differentiation are related at some regulatory level, perhaps through a single multi-gene regulatory factor. Fertilized Ciona eggs were exposed to cytochalasin B for 20 h and then briefly reacted histochemically for acetylcholinesterase activity. Strongly reacting specimens were selected and processed for transmission electron microscopy to reveal regions of muscle ultrastructure. Every acetylcholinesterase-reactive zygote tested contained muscle contractile elements; no example lacking acetylcholinesterase was found with myofilaments and myofibrils. As demonstrated by immunogold labelling, a polyclonal antibody to tropomyosin from Ciona adult body wall reacted differentially with the presumed ultrastructural muscle elements in cleavage arrested zygotes. Site-specific reactions were also observed in larval tail muscle and the siphon muscles of postmetamorphic zooids. PMID- 2226209 TI - Double anterior chick limb buds and models for cartilage rudiment specification. AB - Most models for the specification of the skeletal elements in the developing limb bud are based on a chemical specification well before overt cartilage differentiation. By contrast, a physico-mechanical model proposes that the process of condensation--an early feature of cartilage differentiation--is itself the basis for patterning the elements. The models thus make quite different predictions as to when the rudiments are specified. Double anterior limb buds have been constructed at stages earlier than condensation, with the expectation that, if specification of the humerus occurs before cartilage condensation, then limbs containing two humeri should develop, since the presumptive humerus lies largely in the anterior region. The development of anterior and posterior parts, on their own, was in general, consistent with the fate map; both developed a humerus that was thinner than normal. Double anterior limbs developed two humeri in 28% of cases and a much thicker humerus in 39%. These results strongly support models based on an early specification of limb rudiments and cannot be accounted for by the physical model. Double anterior limbs in which the two parts were from different stages, developed such that a digit 3 could lie adjacent to the radius, giving further striking evidence for early specification and local autonomy of development. PMID- 2226210 TI - Identification in Xenopus of a structural homologue of the Drosophila gene snail. AB - We have cloned a Xenopus cDNA that is related to snail, a gene that is required for mesoderm formation in Drosophila. The cDNA encodes a protein that contains five zinc-fingers that closely resemble those of snail. In the non-canonical parts of the DNA-binding loop, there is almost 90% homology between snail and xsna. The corresponding mRNA (xsna) is expressed strongly at the start of zygotic transcription simultaneously with the transcription factor EF1 alpha. In early gastrulae, xsna is equally distributed between the dorsal and ventral halves of the equatorial zone. The possibility that the capacity to synthesise xsna is more localised before the start of zygotic transcription has been investigated by culturing fragments of stage 8 embryos until xsna is synthesised. The capacity to synthesise xsna at stage 8 is located principally in the dorsal half of the equatorial zone. A small amount of maternal xsna is localised in the vegetal hemisphere before zygotic transcription starts. xsna is not present in isolated animal caps but can be induced by the mesoderm-inducing factors XTC-MIF and bFGF. Synthesis of xsna does not occur autonomously in dispersed cells but is restored when cells reaggregate in the presence of calcium and magnesium. PMID- 2226211 TI - Centrally acting sympatholytic agents in the treatment of congestive heart failure. A review of the literature. PMID- 2226213 TI - Management of menopause when estrogen cannot be used. AB - Estrogen deficiency, whether surgically induced or as a consequence of natural ovarian failure, has destructive effects on many organ systems. With current levels of life expectancy, untreated women may expect to spend a third of their lifetime in this state. Appropriate estrogen replacement therapy (ERT) can avert (if started promptly) or ameliorate these devastating consequences, some of which (osteoporotic fractures, increased cardiovascular morbidity) can be lethal. Nevertheless, from 10 to 20% of postmenopausal women may have significant contraindications to ERT. Treatment of symptoms and improving the quality of life is imperative, yet many physicians abjure intervention, for reasons which are not entirely clear. Recent studies of conventional intervention with sedatives or tranquilisers show results equivalent to placebo therapy. On the other hand, specific agents with demonstrated effectiveness are available for management of the major estrogen-deficiency effects, although none of them are truly adequate replacement for the effect of estrogen itself. PMID- 2226214 TI - Current concepts in the management of sarcoidosis. AB - Sarcoidosis can affect almost every organ. It has diverse clinical presentations and a variable natural history. Lungs and intrathoracic lymph nodes are the most commonly involved tissues. A major challenge to clinicians is the early identification of those patients with aggressive disease in whom therapy might arrest progression. Although lung uptake of 67Ga citrate, elevated serum angiotensin converting enzyme (ACE) levels and elevated T lymphocyte count in bronchoalveolar lavage fluid are all thought to reflect disease activity, they are by no means reliable markers. Because recent studies have shown that corticosteroid treatment does not avert pulmonary fibrosis and permanent impairment of pulmonary function, the use of these agents is restricted to the palliative treatment of disabling symptoms and physiological derangements. Corticosteroids are effective in reducing ocular inflammation, correcting hypercalcaemia, improving pulmonary function and alleviating symptoms related to hepatic, splenic, articular, myocardial, neural and cutaneous involvement. In the small proportion of patients who do not respond to moderate tolerable doses of steroids, alternative drug therapy such as immunosuppressives or immune modulators must be considered. PMID- 2226215 TI - Ticlopidine. An updated review of its pharmacology and therapeutic use in platelet-dependent disorders. AB - Ticlopidine inhibits platelet aggregation induced by adenosine diphosphate (ADP) and most other platelet agonists in ex vivo studies of human platelets. The drug also improves other abnormalities of platelet function seen in patients with cerebrovascular disease, peripheral arterial disease, ischaemic heart disease or other conditions involving platelet hyperaggregation. Abnormal platelet activity has been implicated in a variety of clinical conditions in which patients are at high risk of thromboembolic events, and thus the effectiveness of ticlopidine has been investigated in such patients. Since the initial review of the drug appeared in the Journal, data from several large multicentre studies have shown that ticlopidine has a substantial benefit to offer patients who have experienced transient ischaemic attacks or stroke, and in those with peripheral arterial disease or ischaemic heart disease. Ticlopidine reduces the incidence of further stroke, myocardial infarction or vascular death, and is superior to placebo and aspirin in this regard in studies of patients with recent stroke or transient ischaemic attacks, or intermittent claudication. Ticlopidine is equally effective in both men and women and also improves symptoms of claudication in patients with peripheral arterial disease, and appears to reduce anginal pain. Patients with subarachnoid haemorrhage and sickle cell disease have shown some improvement with ticlopidine administration. The drug reduces thromboembolic events and re stenosis in patients undergoing haemodialysis and cardiac surgery, and appears to prevent the progression of nonproliferative diabetic retinopathy. Ticlopidine in large clinical trials is associated with a higher incidence of adverse effects than placebo and an overall incidence similar to aspirin. Most adverse effects do not require withdrawal of treatment. Gastrointestinal symptoms (particularly diarrhoea) are most common, occurring almost twice as frequently with ticlopidine as with aspirin. Other adverse effects associated with ticlopidine include skin rash, haemorrhagic disorders, and haematological effects; these latter effects require careful monitoring of patients during the initial weeks of therapy. In conclusion, ticlopidine is a valuable addition to the prophylactic treatments available for the management of patients with cerebrovascular disease, peripheral arterial disease or ischaemic heart disease, who present a high risk of thromboembolic events. Although tolerability may be a problem for some patients, the overall benefit conferred by the drug would appear to outweigh this potential disadvantage. Because of its antiplatelet activity, ticlopidine has a promising role in other disorders mediated by platelet dysfunction. However, the precise role of the drug in these additional therapeutic indications awaits clarification with wider clinical experience. PMID- 2226212 TI - Effects of drugs on glucose tolerance in non-insulin-dependent diabetics (Part II). PMID- 2226217 TI - Zolpidem. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential. AB - Zolpidem is an imidazopyridine, a chemically novel nonbenzodiazepine hypnotic agent which acts at the benzodiazepine omega 1-receptor subtype in the brain. With a rapid onset of action and short elimination half-life, it reduces the latency to and prolongs the duration of sleep in patients with insomnia, yet has no major effects on sleep stages when given in dosages of 5 to 20 mg nightly. Rebound effects on withdrawal of the drug have not been observed. Unlike benzodiazepines, zolpidem has no myorelaxant or anticonvulsant effects and its effects on anxiety appear to be minor. While zolpidem aids sedation, and may reduce memory or psychomotor function within the first 2 hours after administration of single oral doses, its use as a surgical premedicant remains to be established. Adverse effects are predominantly CNS and gastrointestinal in nature. Altered pharmacokinetics may lead to an increase in dose-proportionate adverse effects in the elderly and in patients with renal dysfunction. Limited evidence to date suggests that the dependence liability of zolpidem is minimal. Thus, zolpidem is an interesting alternative to benzodiazepines in the treatment of insomnia, with properties that potentially offer worthwhile advantages in this therapeutic area if they are confirmed with wider clinical experience. PMID- 2226216 TI - Fenofibrate. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in dyslipidaemia. AB - Fenofibrate is a lipid-regulating drug which is structurally related to other fibric acid derivatives, such as clofibrate. At the recommended dosage of 200 to 400 mg daily, it produces substantial reductions in plasma triglyceride levels in hypertriglyceridaemic patients and in plasma total cholesterol levels in hypercholesterolaemic patients. High density lipoprotein (HDL)-cholesterol levels are generally increased in patients with low pretreatment values. Fenofibrate appears to be equally effective in diabetic patients with hyperlipoproteinaemia without adversely affecting glycaemic control. The influence of fenofibrate on the plasma lipid profile is sustained during long term (2 to 7 years) treatment. Comparative studies conducted to date have involved only small groups of patients -in overall terms fenofibrate was at least as effective as other fibrates, but larger comparative studies are needed before valid conclusions on its relative efficacy compared with nonfibrate lipid-lowering drugs can be drawn. The influence of fenofibrate on morbidity and mortality from cardiovascular disease has not been studied. Clinical adverse reactions to fenofibrate have mainly consisted of gastrointestinal disturbances, headache and muscle cramps. Transient elevations in transaminase and creatine phosphokinase levels commonly occur. Isolated cases of hepatitis with substantially elevated transaminase levels have been reported. Fenofibrate induces hepatomegaly, peroxisome proliferation and hepatic carcinomas in rodents, but this type of hepatotoxicity has not been observed in humans. The biliary lithogenic index is increased by fenofibrate, but this has not been shown to have increased the incidence of gallstones in treated patients. Thus, fenofibrate offers an effective and well tolerated alternative to clofibrate or other fibric acid derivatives, but its relative efficacy and tolerability compared with other types of lipid-lowering drugs, and its effect on cardiovascular morbidity and mortality, remain to be clarified. PMID- 2226218 TI - Emerging indications for the use of cyclosporin in organ transplantation and autoimmunity. PMID- 2226220 TI - Current treatment recommendations for topical burn therapy. AB - Infections in burn patients continue to be the primary source of morbidity and mortality. Topical antimicrobial therapy remains the single most important component of wound care in hospitalised burn patients. The goal of prophylactic topical antimicrobial therapy is to control microbial colonisation and prevent burn wound infection. In selected clinical circumstances topical agents may be used to treat incipient or early burn wound infections. At the present time silver sulfadiazine is the most frequently used topical prophylactic agent; it is relatively inexpensive, easy to apply, well tolerated by patients, and has good activity against most burn pathogens. In patients with large burns the addition of cerium nitrate to silver sulfadiazine may improve bacterial control. Mafenide acetate has superior eschar-penetrating characteristics, making it the agent of choice for early treatment of burn wound sepsis. However, the duration and area of mafenide application must be limited because of systemic toxicity associated with prolonged or extensive use. Other agents, such as nitrofurazone or chlorhexidine preparations, may be useful in isolated clinical situations. The undesirable side effects of silver nitrate solution limit its use by most clinicians at the present time. PMID- 2226223 TI - Sexually transmitted diseases and HIV-1: interactions in transmission and role in control programs. PMID- 2226219 TI - Angiotensin converting enzyme inhibitors and moderate hypertension. AB - Recently there has been extensive development of orally active angiotensin converting enzyme (ACE) inhibitors in addition to those already marketed, for example, captopril, enalapril, lisinopril and ramipril. It was initially thought that ACE inhibitors were likely to be most useful as antihypertensive agents in conditions in which circulating renin and angiotensin II were elevated. However, it is now clear that they can also lower arterial pressure when plasma renin is not high. In addition, they have beneficial effects in cardiac failure. Thus, captopril, enalapril, lisinopril and ramipril can be used in the treatment of mild to moderate hypertension either alone or in conjunction with diuretics or calcium antagonists. Broadly speaking, efficacy appears to be similar to that of beta-blockers or diuretics. Unfortunately, however, there are no long term studies comparing one ACE inhibitor with another or with other classes of antihypertensive agents. Furthermore, there are no prognostic studies which show that use of ACE inhibitors reduces morbidity or mortality in hypertension. Many new ACE inhibitors are undergoing clinical assessment, including alacepril, cilazapril, fosenopril, perindopril, quinapril and ramipril. The drugs vary, in that some exist in the active form whereas others are prodrugs which are converted to the active agent following absorption. In addition they each possess one of several ligands, for example, carboxyl, phosphinyl or sulfhydryl groups, and so vary in their affinity for ACE. Although many of these agents are renally excreted, a small number are metabolised via the liver (e.g. quinapril and spirapril) and this may prove advantageous in the presence of renal impairment. In common with captopril and enalapril, the new ACE inhibitors inhibit the renin angiotensin system and initial results suggest that they are effective in lowering blood pressure in essential hypertension. Furthermore, they reduce systemic vascular resistance in the absence of a reflex tachycardia. There are a number of adverse effects which are attributable to the pharmacological mechanism of the ACE inhibitors as a group; these include hypotension, particularly in patients with high renin levels, prior diuretic use, renal impairment or in the elderly. Additional adverse effects may relate to chemical structure. The high incidence of adverse effects noted in early studies related to excess dosage and to the presence of a sulfhydryl group, which the more recently developed ACE inhibitors lack. The adverse effects most commonly reported with established and new ACE inhibitors include headache and fatigue, cough, skin rashes, hypotension and diarrhoea. As a group, ACE inhibitors have an acceptable but not negligible adverse effect burden.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2226224 TI - Prevalence of antibodies to human T-lymphotropic virus type 1 (HTLV-1) in an HIV endemic region of Africa. AB - Serum samples from 267 healthy subjects and patients either infected or not infected with HIV-1 in Dar es Salaam, Tanzania, were examined by enzyme-linked immunosorbent assay and western blot techniques for evidence of HTLV-1 infection. Specific antibodies were detected in only 1% of the sera. Positive sera were likely to be from individuals infected with HIV-1. Tanzania and probably the other East African countries are non-endemic for HTLV-1. Prevalences are too low to provide justification for screening of blood donations. However, screening of donor blood for HIV-1 will limit transmission of HTLV-1 by this route as well. PMID- 2226221 TI - Mexiletine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias. AB - As a member of the class Ib antiarrhythmic drugs mexiletine's primary mechanism of action is blocking fast sodium channels, reducing the phase 0 maximal upstroke velocity of the action potential. It increases the ratio of effective refractory period to action potential duration, but has little effect on conductivity. Unlike quinidine it does not prolong QRS and QT (QTc) intervals. In the dosage range 600 to 900 mg daily mexiletine effectively suppresses premature ventricular contractions (PVCs) in 25% to 79% of patients, with or without underlying cardiac disease. In comparative studies the response rate was comparable to that with quinidine or disopyramide. However, the use of antiarrhythmic therapy in patients with asymptomatic arrhythmias is controversial. More importantly, mexiletine abolishes spontaneous or inducible ventricular tachycardia or fibrillation in the short term in 20% to 50% of patients with refractory arrhythmias. Arrhythmia suppression is maintained in 57% to over 80% of these early therapeutic successes in the long term, with mexiletine alone or in combination with another antiarrhythmic drug. As with other antiarrhythmic drugs, there is no substantial evidence that administration of mexiletine after acute myocardial infarction improves long term prognosis. Although the incidence of adverse effects associated with mexiletine is high, the majority are minor gastrointestinal or neurological effects which can be adequately controlled through dosage adjustment. Furthermore, mexiletine has minimal effects on haemodynamic variables, or on cardiac function in patients with or without pre-existing deterioration of left ventricular function, and it appears to have a low proarrhythmic potential. Thus, while the therapeutic efficacy of mexiletine for the prevention or suppression of symptomatic ventricular arrhythmias may be no greater than that of other antiarrhythmic drugs, and less than that of some (e.g. amiodarone), it is effective in a significant proportion of patients refractory to other treatments and can be administered without causing adverse haemodynamic effects to patients with complicating factors such as acute myocardial infarction or congestive heart failure. PMID- 2226222 TI - Ketotifen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in asthma and allergic disorders. AB - Ketotifen is an orally active prophylactic agent for the management of bronchial asthma and allergic disorders. Accumulated evidence indicates that after 6 to 12 weeks of administration, ketotifen significantly reduces respiratory symptoms and the need for concomitant antiasthmatic drugs in about 70% and 50%, respectively, of patients with mild to moderate bronchial asthma. However, absolute improvement in lung function is generally slight. Ketotifen also has pronounced antihistaminic and antianaphylactic properties which result in moderate to marked symptom improvement in the majority of patients with atopic dermatitis, seasonal or perennial rhinitis, allergic conjunctivitis, chronic or acute urticaria or food allergy. Comparative trials with established agents--notably sodium cromoglycate (cromolyn sodium) in asthma and histamine H1-antagonists in allergic disorders--indicate that ketotifen has comparable clinical utility. Unlike inhaled sodium cromoglycate, ketotifen ameliorates the symptoms of asthma, rhinitis and dermatitis when present together in atopic patients. Patient acceptance of ketotifen is good, although sedation can be troublesome in older children and adults for the initial 2 weeks of treatment. Weight gain is another notable effect in a small percentage of patients. Thus, ketotifen appears to be a useful agent for the management of allergic disorders and bronchial asthma, particularly in patients for whom oral therapy is preferred. Although a lengthy run-in period is needed in the treatment of asthma, in those patients who respond, continued reduction in the frequency and severity of symptoms and in the use of additional antiasthmatic drugs can be anticipated. PMID- 2226225 TI - HIV infection surveillance in Mogadishu, Somalia. AB - A group of 89 prostitutes and 45 patients attending sexually transmitted disease clinics in Mogadishu, Somalia were examined for evidence of HIV infection. Both groups reported more than 1 sexual partner routinely and had sexual contacts with prostitutes. There was a significant amount of sexually transmitted diseases (STDs) in these two groups, with 11.2% and 6.7% respectively being culture positive for N. gonorrhoea. Among the prostitutes, 28.1% were positive for antibodies to T. pallidum while only 4.4% of the STD patients were positive. One isolate of N. gonorrhoea was resistant to penicillin. All study participants were negative for antibodies to HIV suggesting an extremely low prevalence of HIV in high risk behaviour groups in the capital city of Somalia. PMID- 2226227 TI - Prevalence of concurrent Chlamydia trachomatis infections among men with gonococcal urethritis in Lusaka. AB - The prevalence of Chlamydia trachomatis infections among male patients with gonococcal urethritis in the sexually transmitted diseases (STDs) clinic at UTH, Lusaka, was determined by two methods to be around 4.7%. Methods used were specific for C. trachomatis (Syva Microtrak), and second isolation of C. trachomatis. The results indicate that with a prevalence rate of 4-7% for concurrent gonococcal and chlamydial infection, it is not financially or medically practical to treat all cases of gonorrhoea in Zambia for possible chlamydial infection, as is advocated in some countries. The findings further suggest that the commercially available Syva Microtrak test should probably be considered positive when one or two monoclonal-stained elementary bodies are seen, rather than ten, to avoid false-negative results. PMID- 2226228 TI - Stroke at Kenyatta National Hospital. AB - Seventy two patients presenting with stroke to Kenyatta National Hospital were studied between January 1986 and January 1987. The majority were from the rural areas. There were about equal numbers between left and right sided hemipareses. The majority of the patients were in their 6th and 7th decades. 22 of the patients were hypertensive. Diabetes mellitus, cigarette smoking, alcohol consumption, and valvular heart disease were some of the other factors associated with strokes. 46% of the patients died while the remainder had residual neurological deficits. PMID- 2226226 TI - Prevalence of gonorrhoea, syphilis and trichomoniasis in prostitutes in Burkina Faso. AB - Prevalence of syphilis, gonorrhoea and trichomoniasis among 127 prostitutes in Ougadougou, Burkina Faso, was investigated. 22% were positive of syphilis, 20% for intracellular gram negative diplococci, and 17% for Trichomonas vaginalis infection. Demographic data revealed that the prostitutes were a young group, with 69% between 15 and 25 years old. 14% of the women were from Burkina Faso; the majority (73%) were of Ghanaian origin. Our data highlight alarming rates of STDs in prostitutes working in Ouagadougou. Education campaigns which consider sociodemographic and cultural characteristics of the prostitutes should be established to reduce these rates. Upgrading of diagnostic capabilities and focal mass drug administration among prostitutes should also be considered. Data for this study were collected at Yalgado Ouedraogo Hospital, Ouagudougou, Burkina Faso, and analyzed at Columbia University School of Public Health and at Montefiore Medical Center/Albert Einstein College of Medicine, New York, USA. PMID- 2226229 TI - Megaloblastic anaemia in Zimbabwe: the pernicious anaemias. AB - This study of 16 patients with pernicious anaemia (PA) (9 males and 7 females); serves as further evidence that the disease is not as infrequent in Africans as the literature stressing its rarity in the past appears to have suggested. The age-old preconceptions about racial incidence; age of onset; and absence of adequate laboratory facilities particularly in the African setting have hitherto greatly contributed to under-diagnosis of this disorder in Africans. PMID- 2226230 TI - Foam slipper in place of the walking heel for lower limb plaster of Paris casts. AB - Avoidable delays in the application of weight-bearing lower limb plaster of Paris casts on our patients caused by shortages of the standard walking heels (rockers) made us try the common and always--available foam slippers in their place. Their use in the treatment of 450 patients is reported here. The slippers performed all the usual functions of the rockers well and there were no complications due to their use. The patients felt very steady and comfortable on them and particularly appreciated the cushioning effect of their soft soles and the fact that they could use the other slipper on the uninjured leg comfortably. On the basis of the excellent results obtained in this study and in view of their cheapness and ready availability, the author recommends a wider use of slippers in place of the conventional rockers. PMID- 2226231 TI - Inter-relationships between HIV infection and other sexually transmitted diseases. AB - The HIV is a typical sexually transmitted disease (STD) agent which depends for its transmission through sex on contact between raw body tissues of infected and uninfected individuals independent of sexual inclination. The dynamics of HIV transmission and its control in a community can be inferred from studying the socio-cultural and epidemiological aspects of acute STD. There is strong evidence to suggest that the main cause of rampant heterosexual transmission of the HIV in sub-Saharan Africa in contrast to the rarer heterosexual HIV transmission in Europe and the USA is the high prevalence of ulcerative STD in Africa. Studying the trend and response to treatment of conventional acute STD are quick and indirect ways of assessing the impact of control measures against AIDS and HIV infection in an HIV endemic area. Further research is needed to determine the extent and detailed mechanism of interaction between HIV infection and other STDs as well as studying the efficacy of AIDS control through control of other STDs. PMID- 2226233 TI - Herpes Zoster Ophthalmicus in a child with acquired immune deficiency syndrome. AB - A case is described of an 8 year old child who presented with Herpes Zoster Ophthalmicus involving the left eye. He had a positive history of pulmonary tuberculosis, repeated hospital admissions and blood transfusion. He was confirmed to have Acquired Immune Deficiency Syndrome. During the course of his followup, he developed cotton-wool spots and perivasculitis in the right eye. The mother was found to be seropositive while the father was seronegative. PMID- 2226232 TI - Conjunctival Kaposi's sarcoma in a patient with acquired immune deficiency syndrome. AB - A patient with confirmed acquired immune deficiency syndrome (AIDS) and disseminated Kaposi's sarcoma was seen in the Eye Clinic, Kenyatta National Hospital, and was found to have involvement of the conjunctiva and lids, confirmed by biopsy. He also had retinal haemorrhages and cotton-wool spots. Kaposi's sarcoma of the conjunctiva may be confused with a subconjunctival haemorrhage. PMID- 2226234 TI - The history of interferon and its use in animal therapy. AB - The history of the discovery and development of knowledge on interferon is reviewed in some depth. Although interferons have been considered a very exciting group of proteins for many years during which they were initially shown to have antiviral effects and lately immunomodulatory and immunoregulatory effects, attempts to use them in the therapy of animal and human disease have been disappointing. The initial problem was to obtain sufficient quantities of purified interferons for use in clinical trials. This was overcome in the 1980's by the use of biotechnological techniques which resulted in the synthesis of adequate amounts of interferons. While beneficial aspects of interferon therapy have been shown in a variety of experiments, both in animals and humans, the great potential for interferon treatment has yet to be achieved. In the body, interferon is produced in such small quantities as compared to the large quantities which have been normally used in therapy and it is well recognized that these proteins, the interferons, are particularly potent. A small group of scientists working from biological principles, originating from U.S.A. and are now being developed in Kenya, have found powerful beneficial effects when relatively low dose of IFN-alpha is applied orally to animals and humans, particularly for the treatment of AIDS and East Coast fever. It is now known that interferons are only a part of the cytokine network and indirect and direct effects of interferon can occur on cells to change their behaviour. Many of these effects are non-specific and have a general effect on the course of diseases which, hopefully, can be translated into effective broad spectrum therapy, for man and animals. PMID- 2226235 TI - Efficacy of Kemron (low dose oral natural human interferon alpha) in the management of HIV-1 infection and acquired immune deficiency syndrome (AIDS). AB - One hundred and ninety nine symptomatic and 5 asymptomatic patients seropositive for the human immunodeficiency virus type 1 (HIV-1) were treated with KEMRON, a natural human interferon alpha (nHIF alpha) stabilized in a complex polysacchariche carrier. Treatment was given for at least 10 weeks at a daily oral dose of approximately 2.0 IU of nHIF alpha per kg body weight. Karnofsky performance score increased from an average of 60.5 on entry into the study to 100 by the 10th week after treatment. Similarly, common clinical complaints associated with HIV-1 infection rapidly reduced per patient from an average of 3.8 to 0.05 and 0 by week 8 and 10 of treatment. Eighteen of the patients serodeconverted by both ELISA and western blot assays during the study period. These observations suggest that KEMRON used as recommended is beneficial in HIV-1 seropositive individuals. PMID- 2226237 TI - Kemron. Low dose natural human interferon alpha for oral administration (general information and technical details). PMID- 2226236 TI - Treatment of HIV infections and AIDS: new horizons. AB - Treatment of HIV infections has involved the use of antiviral drugs as well as those drugs that act against opportunistic infections. Immune modulators have also been used. A review of these drugs is reported emphasizing on those which have great promise in the clinical management of HIV infections in the light of our present knowledge on immunopathology of the disease. PMID- 2226238 TI - Response of Pleurotus ostreatus to cadmium exposure. AB - The possibility of utilizing agroindustrial wastes in the production of edible, high-quality products (e.g., mushrooms) implies the risk of bringing toxic substances, such as heavy metals, into the human food chain. Thus, growth in the presence of cadmium and cadmium accumulation limits have been studied in the industrially cultivated fungus P. ostreatus. Fruit body production is substantially unaffected in the presence of 25, 139, and 285 mg Cd/kg of dried substrate. Cadmium concentration in fruit bodies is related to cadmium substrate level, the metal being present at higher levels in caps (22-56 mg/kg dry wt) than in stems (13-36 mg/kg dry wt). Concentration factor (CF), very low in the controls (about 2), further decreases in treated specimens. The presence of a cadmium control mechanism in this fungi species is suggested. Fruit body cadmium levels could, however, represent a risk for P. ostreatus consumers, according to FAO/WHO limits related to weekly cadmium intake. PMID- 2226239 TI - Metabolic effects of kraft mill effluents on the eel Anguilla anguilla L. AB - Yellow eels (Anguilla anguilla L.) with an average weight of 60 g were used in this experiment. The fish were caught in June/July at the Aveiro Lagoon on the Portuguese West Coast, transported to the Department of Biology, Aveiro University, and kept in aerated aquaria for 1 week before the experiment started. The eels were then exposed for 1 and 3 weeks to 75 and 50% of the kraft pulp mill effluent. The eels exposed to the kraft pulp mill effluent developed an increase in red blood cell number per cubic millimeter and several biochemical changes, such as an increase in plasma lactate and sodium and a decrease in plasma pyruvate and potassium. Histological examination of the experimental eels exposed to the 50% kraft pulp mill effluent revealed deep alteration of the tissue structure, such as disruption of the skin and edematous hypertrophy of covering epithelial cells in secondary gill lamellae. The kidney had damage of the renal tubules. The liver developed necrosis supported by a significant decrease in GOT and GPT activity. The spleen had an increase in blood content as well as in pigment centers. Previous results indicated the kraft pulp mill effluent causes tissue damage and consequent metabolic changes in the eel Anguilla anguilla L. PMID- 2226240 TI - In vivo recovery of glycogen metabolism in hemolymph and tissues of a freshwater field crab Barytelphusa guerini on exposure to hexavalent chromium. AB - The in vivo toxic effects of hexavalent chromium (20 mg/liter) on hemolymph glucose, tissue glycogen, total free sugars, and active and total phosphorylases of an edible, freshwater crab Barytelphusa guerini were studied. In a 15-day exposure span followed by a 15-day postexposure recovery, the time-course alterations in these constituent segments of the glycogen metabolism indicate an inconsistent depletion in metabolite levels and elevated enzyme activities during exposure period as well as hyperglycemia. An insignificant recovery was observed in these parameters on the 15th day of the postexposure phase. PMID- 2226241 TI - Effect of copper sulfate on hematology, blood chemistry, and hepato-somatic index of an Indian catfish, Heteropneustes fossilis (Bloch), and its recovery. AB - The present communication deals with the effect of copper sulfate (0.25 ppm) on hematology, blood chemistry, and hepato-somatic indices of an Indian catfish, Heteropneustes fossilis (Bloch) and its recovery from intoxication. Analysis of various parameters was made after 24 hr, and 5, 10, 20, and 30 days of CuSO4 exposure. Subsequently, the fish were allowed recovery periods of 24 hr and 5 days in normal water. Changes in various parameters from normal values during exposure and recovery were recorded and probable reasons for alterations have been discussed in detail. PMID- 2226242 TI - Fish embryos as teratogenicity screens: a comparison of embryotoxicity between fish and birds. AB - Early life stage (ELS) toxicity experiments were carried out with zebra fish (Brachydanio rerio) and rainbow trout (Salmo gairdneri) and 10 chemicals used in the rubber industry. Several of these chemicals appeared to be teratogenic. A good correlation (r = 0.95) was found between the 7-day EC50 for zebra fish and the 60-day EC50 for rainbow trout for total embryotoxicity (embryolethality and malformations). The S. gairdneri test appeared to be slightly more sensitive than the test with B. rerio. It is therefore concluded that this short-term test is a good alternative for the long-term test with S. gairdneri. A remarkably good correlation (r = 0.90) was found between the ED50 for chicken embryotoxicity reported in the literature and the EC50 for embryotoxicity for both zebra fish and rainbow trout. This may, among other things, be explained by similarities in embryonic development and the absence of maternal and placental metabolism of the toxicants in tests with eggs of both fish and birds. It may therefore be concluded that both the short-term ELS test with B. rerio and the chicken egg test have the same predictive power for mammalian teratogenicity; i.e., both are suitable screening tests for direct-acting teratogens. PMID- 2226243 TI - Effect of 3,4-dichloroaniline and metavanadate on Daphnia populations. AB - Fourteen continuously fed populations of Daphnia magna were exposed to 3,4 dichloroaniline (3,4-DCA) or metavanadate and monitored for 20 (two controls), 14 (six with metavanadate), and 8 (six with 3,4-DCA) weeks. The controls showed a damped oscillation. Low concentrations of either 3,4-DCA or metavanadate stimulated the first population peak. High concentrations of metavanadate rendered population peaks less regular, and at the highest metavanadate concentration, one population perished. High concentrations of 3,4-DCA slightly reduced population size. Four periodically fed populations of D. magna were also monitored. The more they were fed, the larger they grew. In the continuously fed populations, ephippia were formed at and just after the population peaks. No ephippia were noted in the periodically fed populations. Metavanadate promoted the formation of ephippia (NOEC 0.56 mg/liter), and 3,4-DCA depressed sexual reproduction at all concentrations tested (6, 12, and 24 micrograms/liter). The population dynamics of the controls were compared with those predicted by Kooijman's model (1986a, in The Dynamics of Physiologically Structured Populations (J.A.J. Metz and O. Diekmann, Eds.), pp. 266-297, Springer Lecture Notes in Biomathematics; 1986b, J. Math. Biol. 23, 163-185) for growth and reproduction of individual daphnids. In general, there is reasonable agreement between model predictions and observations, but some adjustments to the model may be necessary. PMID- 2226244 TI - Influence of inorganic lead on the biochemical blood composition of the eel, Anguilla anguilla L. AB - Yellow eels (Anguilla anguilla L.) with an average weight of 50 g were caught in September in the Aveiro Lagoon on the Portuguese West Coast and kept in aerated aquaria for 1 week before the experiment started. The eels were exposed to an inorganic lead concentration of 300 micrograms Pb/liter for 30 days. Differential white blood cell count showed an increase in the number of lymphocytes in exposed fish. Blood hemoglobin and number of red blood cells per cubic millimeter showed no differences between the control and the exposed fish. Biochemical analyses of blood composition, such as plasma glucose, total plasma protein, total plasma cholesterol, and sodium and potassium plasma, showed no differences between treated and control animals. Plasma lactate levels increased in treated animals compared with those in controls. PMID- 2226245 TI - Retention of cadmium in cadmium-naive normal and iron-deficient rats as well as in cadmium-induced iron-deficient animals. AB - The retention of cadmium was investigated in cadmium-naive normal and iron deficient rats in comparison to rats with cadmium-induced iron deficiency. Rats subchronically (4 weeks) exposed to dietary cadmium (28, 56, 112 ppm Cd and 28 ppm Fe) received a radioactively labeled dose of 2 mumol Cd/kg body wt; acutely (no cadmium exposure with diet) treated rats received doses between 1 and 8 mumol Cd/kg body wt. Two animals of each group received iron (1 mumol/kg as 59FeSO4 in order to monitor iron absorption in parallel. After a period of 4 weeks of feeding a cadmium-fortified diet, the test dose was administered and after a 2 weeks period 109Cd and of 59Fe retention was determined. The results showed in part an unexpected pattern of cadmium retention: subchronic feeding of cadmium induced iron deficiency. This implies an immediate interaction between the two metals with regard to intestinal transfer of iron. The retention of iron was increased in the Cd-induced anemia to the same extent as that in iron deficiency induced by iron restriction. Cadmium retention in iron deficiency induced by iron withdrawal also showed a marked increase, which implies that iron deficiency stimulates the intestinal transfer system for both metals in a similar way. Contrary to this effect, the cadmium retention in cadmium-induced iron deficiency was reduced to about 30% of control values. A self-induced aggravation of the body cadmium burden, as a consequence of the iron deficiency which is known to result from subchronic exposure to feeding of dietary cadmium, was thus excluded. PMID- 2226246 TI - Incorporation of a subacute test with zebra fish into a hierarchical system for evaluating the effect of toxicants in the aquatic environment. AB - Single-species laboratory tests were used to assess the acute toxicity of halogenated phenolic compounds. No single test system was most sensitive to all of the compounds examined, substantial variations in the sensitivity of the various organisms were noted, and there was no correlation between the toxicities assayed with different test systems. The zebra fish (Brachydanio rerio) embryo/larvae system was used to examine subacute effects using two of the compounds, and a protocol was developed with 6 weeks preexposure to the toxicant. Preexposure decreased the lowest observable effect concentration by a factor of about 4, and the effect was completely reversible during a 6-week postexposure period in the absence of the toxicant. An enclosed system for carrying out the zebra fish embryo/larvae test was developed and evaluated with three neutral volatile compounds: the median survival time and the frequency of occurrence of deformation were examined as end points. The effect of pH on toxicity was evaluated in buffered media for four of the test systems: toxicity increased markedly at the lower pH values, and it could be shown that the ionized forms of the phenols were not the only contributors to toxicity. It is proposed that the zebra fish system incorporating preexposure could be incorporated into a hierarchical system using a range of organisms for assessing acute toxicity in single species under laboratory conditions and multicomponent systems simulating natural ecosystems. PMID- 2226247 TI - Evaluation of the isobologram method for the assessment of mixtures of chemicals. Combination effect studies with pesticides in algal biotests. AB - The aim of this paper is an evaluation of isobolograms, a method proposed for the assessment of combined effects of chemicals. In order to examine potentials and shortcomings of this approach for ecotoxicological purposes, algal biotests with selected pesticidal compounds were performed. Additivity, as defined by the model, is demonstrated for the combination of atrazine and metribuzin for different combination ratios, response levels, and parameters. Subadditivity is shown for amitrole and glufosinate-ammonium. The results and inherent biometrical features are discussed in terms of criteria considered suitable for comparative evaluation of biometrical models for the assessment of mixtures of chemicals. PMID- 2226248 TI - [Biosocial orientation of education and health in society]. PMID- 2226249 TI - [Local health systems and the medical job market: results of a study on preferences as to geographic location]. PMID- 2226250 TI - [The process of work and permanent education of health personnel: reorientation and trends in Latin America]. PMID- 2226251 TI - [Variables related to the academic success of the medical students at the Universidad Autonoma de Nuevo Leon, Mexico]. PMID- 2226252 TI - [Changes in the epidermal growth factor receptors in the liver cells of rats in N nitrosodiethylamine-induced hepatic carcinogenesis]. AB - A sharp decrease in the number of epidermal growth factor receptors (EGF-R) in the rat liver plasma membranes had been found at different stages of diethylnitrosamine-induced carcinogenesis. The complete loss of high-affinity binding sites for EGF did not prevent EGF-dependent autophosphorylation of EGF-R. Hepatocytes from the rat liver tumors in the primary culture had two classes of EGF-R: high and low affinity ones, though their number had been twice less than in the normal hepatocytes. The dynamics of internalization and down-regulation of EGF-R was very similar in the primary culture of transformed and normal hepatocytes. It testifies that there are some factors of microenvironment in the liver during carcinogenesis which cause the loss of EGF-R (down-regulation) and a decrease of their affinity (activation of protein kinase C). A possible autocrine or paracrine nature of these factors is discussed. PMID- 2226253 TI - [The modifying effect of ortho-cresol on benzo(a)pyrene-induced carcinogenesis in mice]. AB - A modifying influence of ortho-cresol (o-cresol) on the carcinogenic effect of benzo(a)pyrene (B(a)P) in their combined peroral administration to CC57Br mice has been revealed. During the simultaneous administration of the o-cresol (1 mg) and B(a)P (1 mg) the rate of tumours, their multiplicity index, the degree of malignancy increased and the latent period shortened. In case of o-cresol administration before or after B(a)P (in the same doses) the decrease of carcinogenic effect has been revealed. In case of simultaneous administration of 10 mg of the o-cresol and 5 mg of the B(a)P the tumor incidence did not change in comparison with the animals of the control group which received only B(a)P. But their progression was hampered which was confirmed by a decrease of the malignancy rate, frequent occurrence and prolongation of the period of the malignization beginning. PMID- 2226255 TI - [The rate of macrophage inclusion in the elimination of tumor cells when administered to syngeneic animals]. AB - A degree of destruction of tumour cells after their inoculation to a syngenic recipient correlates positively with sensitivity to the lytic effect of macrophages. A clear-cut participation of macrophages in elimination of tumours cells can be detected 8 h after their inoculation. PMID- 2226254 TI - [The role of nitrites in carcinogenesis]. AB - Data from literature as well as the results of the author's investigations on the genotoxic and carcinogenic effects of sodium nitrite (SN) are presented. Carcinogenicity of SN detected in animal experiments proved to be connected with the formation of nitroso compounds from endogenous nitrosable precursors. Sodium nitrite possessed the transforming and promoting effects in the cell cultures as well as the mutagenic effects in the bacterial systems where predominant effect of SN as compared with N-nitrosodimethylamine (NDMA) was registered. The prolonged pretreatment with SN amplified the liver DNA damage in rats in case of NDMA endogenous synthesis. PMID- 2226256 TI - [The effect of biocarbazine on the indices of humoral and cellular immunity in mice]. AB - Biocarbazin (5-3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide) when administered in different doses and schedules depressed the primary immune response of mice to erythrocytes (SE). A dose-dependent effect on the immunosuppression degree is revealed. Both the inductive and productive stages of antibody formation are sensitive to the immunosuppressive action of the agent. Under certain conditions biocarbazin induced a sharp suppression of humoral immune response. At the same time, it enhanced significantly the delayed-type hypersensitivity (DTH) response to SE. PMID- 2226257 TI - [The expression of an antigen interacting with monoclonal antibody IB4 on the surface membranes of normal human leukocytes and in lymphoproliferative diseases]. AB - Monoclonal antibody (MAb) 1B4 of IgG3 isotype reacting with 55 +/- 10% peripheral blood lymphocytes was obtained. MAb 1B4 is bound with 100% of B and NK cells and 50-70% of T cells in blood. The most part of CD8+ cells (60-100%) and approximately 50% of CD4+ cells belong to 1B4+ population. T-ALL cells do not express 1B4 antigen. Analysis of reactivity of MAb 1B4 with transformed malignant cells has shown that 1B4 antigen appeared in the process of differentiation of B lymphocytes at the state of pre-B cells and disappeared with activation of B lymphocytes and transition to plasma cells. PMID- 2226259 TI - [The effect of the bone marrow fibroblasts from patients with malignant diseases of the blood system on the colony-forming capacity of granulomonocytic precursor cells]. AB - The inhibiting activity of bone marrow fibroblasts and their ability to sustain survival of granulocytic cell precursors have been studied in patients with chronic myelocytic leukemia, chronic lymphoproliferative disorders, acute leukemia, myelodysplastic syndrome. Fibroblast conditioned medium inhibits proliferation of granulomonocytic precursors stimulated by leucocyte feeder layer or leucocyte conditioned medium. The effect depends both on the presence of monocytes and the specificity of the disease. The inhibitory effect is related with long-ranged factors. Bone marrow fibroblasts are able to sustain survival of hemopoietic precursors via humoral and cell-cell mechanisms. The regulatory role of bone marrow fibroblasts in hemopoietic disorders is discussed. PMID- 2226258 TI - [Lymphocyte proliferation and differentiation in chronic lympholeukemia]. AB - Proliferative activity and differentiation levels of lymphocytes of lymph nodes and peripheral blood of practically healthy people and patients with chronic lymphocytic leukemia have been studied using the present physicochemical methods (autoradiography with labelled DNA and RNA precursors, microspectrocytometry, NMR spectroscopy, kinetic formaldehyde method, etc.). The following points have been stated: stage character of changes in normal and leukemic cells, differences in synthesis of nucleic acids in different periods of the cell cycle in norm and under chronic lymphocytic leukemia, proliferation peculiarities of lymphocytes in lymph nodes and in blood, presence of DNA defects in the process development, changes in lipids of lymphocytes and blood plasma at early stages of the disease and in the process of its development. PMID- 2226260 TI - [Tumor-induced immunosuppression in breast cancer patients]. AB - A comparative study of immunological reactivity of healthy volunteers and cancer patients with different stages of the disease was carried out. The study of 8 types of suppressor cells, chemoreceptor sensitivity and blast transformation of lymphocytes, natural killer cells, the level of immunoglobulins, regulatory subpopulation of lymphocytes, etc., has revealed several alterations in regulatory and effector links of immunity in the patients with late stages of the disease. The detailed immunological monitoring in the course of varying schemes of treatment is emphasized. PMID- 2226261 TI - [The induction of tolerance in mice for a human melanoma graft]. AB - Mouse skin allografts and intramuscular BRO human melanoma xenografts were successfully established in phenotypically normal mice after inducing immunological tolerance in the recipients. Tolerance was achieved by inoculating allogenic embryonic liver cells after the whole-body irradiation. No immunological rejection was evident in BRO xenografts for 34 days after transplantation. During this period the BRO cells invaded neighboring tissues and formed distant micrometastases in the lungs. PMID- 2226262 TI - [The hormonal sensitivity of a transplantable adenocarcinoma of the large intestine]. AB - It was found that repeated transplantation of ACATOL strain cells resulted in a loss of their sensitivity to growth-stimulating effect of pentagastrin. The effect of gastrin receptor antagonist proglumide, on ACATOL cells growth was inconstant. ACATOL tumor was sensitive to VIP and glucagon in vitro (as shown by adenylate cyclase activity assay), that makes the model promising for selecting potent hormone drugs against colorectal cancer. PMID- 2226264 TI - [The characteristics of the incorporation of the 14C-glucose label into the total lipids of the organs and tissues of Wistar rats with Guerin's carcinoma under differing nutritional conditions]. AB - Peculiarities of 14C-glucose label incorporation into total lipids (TL) of organs, tissues, blood serum and tumors in rats with the Guerin carcinoma under different nutrition conditions have been studied. It is determined that after recycling 14C-glucose is used in TL synthesis of organs, tissues, tumor which may be again involved in the process of metabolism, that evidences for the function of the synthesis mechanism and mobilization of TL. With an increase of tumor mass the specific activity of label in TL of organs and tissues decreases. In contrast to organs and tissues, the tumor involves 14C-glucose into synthesis of own TL independent of nutrition conditions, their level does not decrease in starvation. PMID- 2226263 TI - [The proliferative kinetics and acid-soluble proteins of the nuclear chromatin in tumor cells with a modified polyamine level]. AB - The inhibition of polyamine synthesis by DFMO (2.7 x 10(-3) M) resulted in a decrease of proliferation rate of L and OH-1 cells. The patterns of acid-soluble nuclear proteins were studied by the SDS electrophoresis. The content of protein fraction with molecular weight 25 kD was shown to correlate with the rate of proliferation of cell cultures. PMID- 2226265 TI - [The mutagenicity of animal carcinogenic agents of natural origin]. AB - The current data from literature on the mutagenicity of carcinogens of natural origin are reviewed. A high correlation between carcinogenicity and mutagenicity of this group of agents is established. PMID- 2226266 TI - [Dextran-ferrite distribution in the body of animals in a nonuniform permanent magnetic field]. AB - Dextran-ferrite (DF) was injected via the femoral artery to the dogs and followed by local magnetization (induction 0.3 T, grade 0.024 T/cm). It has been shown that the local retention of the iron in some tissues of the leg was 3-5 times as high as the control. The magnetization did not increase the local retention of the iron after intravenous injection of DF to mice and rabbits. PMID- 2226267 TI - [A chronobiological analysis of the lymphocyte dehydrogenase activity in the peripheral blood of rats with Walker 256 carcinosarcoma]. AB - In a series of experiments the alpha-glycerophosphate dehydrogenase and succinate dehydrogenase (SDH) activities were daily determined simultaneously by the cytochemical method in peripheral blood lymphocytes of normal rats and those with the Walker carcinosarcoma. Using an original algorithm a hierarchy of biorhythms was singled out by a computer according to individual changes in the dehydrogenase activity for each rat. The mean level of succinate dehydrogenase activity was higher than that of alpha-glycerophosphate dehydrogenase. A set of discovered biorhythms and their representation were identical in the both enzymes. The tumor transplantation caused changes in the phase coordination of investigated dehydrogenases in all rhythms and promoted an increase of the succinate dehydrogenase amplitude as compared with the alpha-glycerophosphate dehydrogenase amplitude in certain rhythms. It is concluded that biorhythmological parameters of these enzymes may be used for characterization of the tumor-bearing host. PMID- 2226268 TI - [The enhancement under the action of a limited diet of the antimetastatic effect due to macrophage activation in mice with Lewis carcinoma]. AB - An antimetastatic effect associated with macrophage activation by liposome encapsulated glucosaminylmuramyldipeptide was found to enhance in malnourished mice with the Lewis lung carcinoma. These changes were not matched by further increase in the functional activity of macrophages. It has been suggested that enhancement of the antimetastatic effect in malnourished animals is due to the inhibition of neovascularization necessary for the beginning of metastatic exponential growth. The induction of neovascularization may be caused by the tumor necrosis factor, main product of activated macrophages. PMID- 2226269 TI - Post-contraction variations in motor pool excitability. AB - Previous evidence has shown a marked increase in motoneuronal excitability during muscle contraction and decreased post-contraction excitability. This post contraction inhibition has been shown to persist up to 800 msec following the end of contraction (Gottlieb and Agarwal, 1973) and apparently continues with gradual recovery up to one minute (Enoka, Hutton and Eldred, 1980). These effects have been attributed in part to influences of muscle receptors on the homonymous motor pool. The purpose of the present study was to observe the time course of short term post-contraction effects, following a maximum isometric contraction, on excitability of the homonymous motoneuronal pool as measured by the Hoffmann reflex. Each of five subjects lay supine on a table with shoulder blocks to prevent movement during resisted plantar flexion. The subject's preferred foot was placed in a stirrup attached to a force gauge which measured tension. Recording electrodes were applied over the soleus muscle, and M- and H-responses were evoked by percutaneous electrical stimulation of the tibial nerve at the popliteal fossa. The stimulus strength was set to elicit a control H-reflex at rest of half the magnitude of the maximum H-reflex value. For each trial the subject performed a 6 s maximum contraction of the triceps surae muscle group, beginning on one visual signal and ending on a second visual signal. The H-reflex was elicited at semi-random intervals prior to and after the visual signal to relax. Increased H-reflex excitability was observed during muscle contraction followed by a marked decrease in evoked amplitudes with gradual recovery following the end of contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226270 TI - Electrophysiologic signs of sensory fiber lesion in spinal amyotrophies and the role of physiologic variations of sensory finger innervation pattern. AB - In 33 patients, 30 to 64 years old, with spinal amyotrophy and brachial paresis, the sensory symptoms and electrophysiologic signs were analyzed. The paresthesias were felt most often in the ulnar nerve innervation region. The motor conduction velocities, terminal latency quotient, sensory conduction on direct nerve stimulation were within the limits of normal in both median and ulnar nerve. On percutaneous stimulation normal values were obtained for median nerve, and significantly slower for ulnar nerve innervation region. In four cases no nerve potential was obtained over the ulnar nerve with stimulation of the fifth finger. The nerve potential over the ulnar nerve was elicited mostly by stimulation of median nerve innervated fingers. Congenital variations of sensory innervation pattern were considered, which may increase the liability to destruction. PMID- 2226271 TI - Radiation-induced brachial plexopathy: clinical and electromyographical (EMG) considerations in 13 cases. AB - The purpose of this study was to determine the clinical and electromyographical characteristics of the initial picture, and the subsequent course of the radiation-induced brachial plexopathy. The AA. studied 13 females affected by infiltrating carcinoma of the breast, who underwent a radical mastectomy with removal of the axillary cavity, followed by radiotherapy (total dose was 50 Gy per cycle). The symptom-free interval between the end of radiotherapy and the appearance of symptoms varied considerably (from one month to 15 years). The initial clinical picture presented pain (5 cases), paresthesia (6 cases) and motor deficit (8 cases). EMG examination showed a pluriradicular denervation in 10 cases (with a very frequent damage of the lower roots of the plexus) and a monoradicular denervation in 3 cases. In 6 cases it was possible to carry out a follow-up with repeated tests for 3-17 years after radiotherapy. The role of the EMG in the diagnosis and prognosis of this plexopathy is then discussed. PMID- 2226272 TI - Surface EMG and motor unit activity of partially denervated human muscle during fatiguing submaximal isometric contraction. AB - The extent to which the normal fatigue compensatory mechanisms are disturbed in partially denervated muscles was investigated in human patients. Surface EMG, as well as motor unit electrical and mechanical activity, were analyzed from the partially denervated first interosseous muscle, during fatiguing isometric submaximal contraction. The EMG power and frequency changes which reveal the local fatigue process of healthy muscle have not been systematically found. Motor unit firing rate changes were rather normal and twitch contraction time did not increase during the fatiguing exercise. Differences between normal and partially denervated muscles could be explain by the occurrence of a central fatigue process more or less important in neurogenic lesions. PMID- 2226273 TI - Aging and quantitative sensory thresholds. AB - Cutaneous thresholds for vibration and thermal sensitivity were quantitated at the index finger and great toe in 54 subjects without obvious neurological disease. Twelve patients over sixty years of age also consented to standard nerve conduction studies which proved normal. Vibration thresholds progressively increased with age to a significant degree at the finger (p less than 0.05), and especially at the toe (p less than 0.001). Thermal sensitivity thresholds showed no significant relationship with age. These findings confirm the clinical notion that vibration discrimination decreases with normal aging, especially in the toes. PMID- 2226274 TI - Forearm median nerve conduction velocity in carpal tunnel syndrome. AB - Reduced velocity of median nerve conduction in the forearm of patients with carpal tunnel syndrome (CTS) has been attributed to an artifact of the electrodiagnostic method rather than pathophysiologic changes in the forearm segment. Standard nerve conduction velocity (NCV) tests measure the forearm segment in combination with the distal latency and this may not represent an accurate assessment of conduction in the proximal portion of the nerve. A new technique of direct evaluation of the forearm median nerve was developed by the stimulation and recording of the forearm nerve action potential (FNAP) proximal to the wrist. The FNAP measurement was compared to the usual NCV in persons with CTS and control subjects. Forearm median nerve conduction velocities in the CTS group were significantly slower (p less than 0.05) than normal subjects using both FNAP and standard NCV techniques. The finding of decreased conduction speeds by the direct measurement of the forearm segment confirms that the reduced speeds derived from NCV are valid and suggests that retrograde degeneration of the nerve axons may result from entrapment in the carpal tunnel. PMID- 2226275 TI - Transmission of acoustic or vibratory signals from a contracting muscle to relatively distant tissues. AB - In 20 normal subjects, acoustic or vibratory signals generated during sustained voluntary isometric contraction of the biceps brachii muscle were recorded directly over the muscle belly. The signals were also recorded simultaneously at a distance from the contracting biceps muscle over the posterior upper arm near the triceps muscle. Frequency amplitude spectra (FAS) of the recordings were determined. The amount of transmission of the most dominant vibratory signal from the biceps muscle to the posterior arm was estimated from the amplitude ratio of similar frequency peaks in the FAS obtained from recordings in these two separate regions. The mean amplitude ratio was 0.46. This finding suggests that when several groups of muscles are contracting simultaneously, there may be significant transmissions of acoustic signals from one muscle to the other. These transmissions could potentially interfere with the selective recording of sounds produced by a specific muscle. PMID- 2226276 TI - Refractory studies in early detection of carpal tunnel syndrome. AB - We studied refractory periods of the median sensory nerves in 10 patients with mild carpal tunnel syndrome (CTS), and compared them with the median sensory refractory studies on normal subjects. Our data showed that relative refractory period (RRP) studies are useful in diagnosing early CTS. PMID- 2226277 TI - Technical approaches to hemisphere-selective transcranial magnetic brain stimulation. AB - Clinical application of transcranial magnetic brain stimulation is mainly used to determine central motor conduction times. With the stimulation coil (Magstim 200, Novametrix) centered conventionally over the midline of the skull convexity and using high stimulus intensities, which are often required in pathological states, the motor cortices of both hemispheres are usually activated simultaneously. Under this condition it is not possible to determine from which hemisphere the descending excitatory volleys to a particular motoneurone pool originate and how the input to the lower motoneurons is organized (uni-/bilateral, ipsi /contralateral). This limitation can be overcome by two different techniques for selective stimulation of the motor cortex of one hemisphere without coactivation of the other even when using maximal stimulus intensities: 1. A large 12 cm (outer diameter) stimulation coil could be used for selective stimulation when a) the magnetic field radiated over the non-stimulated hemisphere is modified by using a prototype coil shield covering the half of the coil over the nonstimulated hemisphere in combination with b) placing the coil away from the midline towards the preferentially excited hemisphere. The coil shield consists of a sheet of a nickel iron alloy which alters the time course of the induced currents by reducing the initial rate of current intensity change (dI/dt). 2. The use of a smaller 6.5 cm (outer diameter) coil also provided a useful tool for selective stimulation of one hemisphere but was restricted to subjects with low excitation thresholds. In subjects with high excitation thresholds the described use of the large stimulation coil is advisable. PMID- 2226278 TI - Effect of corticosterone and dexamethasone on glucocorticoid receptor in lactating rat mammary gland. AB - The effects of either a single dose or long-term administration of corticosterone or dexamethasone 21-acetate (Dex Ac) on glucocorticoid receptor concentration in mammary gland cytosol of lactating adrenalectomized rats were investigated. Adrenalectomy on lactation day 7 failed to affect the glucocorticoid receptors significantly. Both the natural and synthetic steroid caused a rapid decrease of receptor binding in the cytosol but the time course of glucocorticoid receptor depletion was different. Complete depletion of cytosol receptor was observed after both a single s.c. Dex Ac dose (20 micrograms/100 g) and after long-term oral treatment (10 micrograms/ml saline as drinking solution for 6 days) immediately after the last steroid dose. In the first case the depletion was still observable at 24 h after the injection without any change in Kd. In contrast, prolonged administration of Dex Ac maintained the receptor binding low even for 48 h after steroid withdrawal and resulted in an increased Kd. Even after an additional day the binding did not exceed the level of 50% of controls. By that time, however, Kd has returned to normal values. On the other hand, a single dose of corticosterone (100 micrograms/100 g) as well as long-term corticosterone treatment (100 micrograms/ml saline as drinking solution for 6 days) reduced the glucocorticoid receptor concentration only to 60% and 25%, respectively. Twenty four hours after the hormone administration the receptor binding returned to control level, no change in Kd being observed. It was concluded that Dex Ac, but not corticosterone, down-regulates the glucocorticoid receptors in mammary gland cytosol of lactating rats. PMID- 2226279 TI - Influence of melatonin on thyroid secretion in pinealectomized rats. AB - The influence of a single dose of melatonin administered to pinealectomized and sham operated rats at different times of day on serum T3, T4 concentrations was investigated. It was found that such melatonin influence depends upon a time of day. Both pinealectomy and exogenous melatonin did not influence the thyroid activity in the morning. The most remarkable pineal effect on the thyroid appeared during the night. PMID- 2226280 TI - Effect of pinealectomy on mitotic activity of adrenal cortex in rats subjected to unilateral adrenalectomy. AB - The effect of pinealectomy on the adrenal growth in unilaterally adrenalectomized rats was studied by evaluation of the mitotic activity of adrenocortical cells on the fifth and tenth day after operation. It was found that pinealectomy resulted in an about double increase of mitotic index on the 5th day after unilateral adrenalectomy, and on the 10th day the stimulatory effect of pinealectomy became less significant. PMID- 2226281 TI - Thyrotropin receptors, thyroid hormones and thyroglobulin in patients with Hashimoto's thyroiditis. AB - TSH receptors in plasma membranes of thyroid nodular and perinodular tissue and the concentration of thyroid hormones and thyroglobulin in serum were estimated in patients with Hashimoto's thyroiditis (HT) and in six persons with scintigraphically cold thyroid nodules (AFN). In perinodular tissue of HT patients specific binding of 125I-bTSH was found to be significantly decreased (1.50 +/- 0.13%; mean +/- S.E.) as compared with AFN patients (2.79 +/- 0.53%), whereas any significant difference in hormone binding to nodular tissues between both examined groups was not detected. Scatchard analysis of TSH binding revealed two kinds of binding sites for both thyroid tissues of all examined patients. The capacity of high affinity binding sites in both thyroid tissues of HT patients was found to be decreased (3.92 +/- 0.86 fmol/mg protein in nodular tissue and 5.93 +/- 1.16 fmol/mg protein in perinodular tissue) in comparison with these tissues of AFN patients (18.80 +/- 18.36 and 32.24 +/- 33.38, respectively). Any differences in dissociation constant and capacity of low affinity binding sites between analysed groups were not observed. Serum TSH levels of HT patients were higher than these in AFN patients and were not significantly changed after surgical treatment. Any difference in triiodothyronine (T3) levels between analysed groups was not detected, while the concentration of thyroxine (T4) was lower in HT than in AFN and significantly decreased after the excision of thyroid gland. Thyroglobulin levels were significantly changed after surgical treatment in both analysed groups. PMID- 2226282 TI - Failure to demonstrate the effect of glucose on insulin removal by perfused rat liver. AB - The effect of glucose on insulin removal by perfused liver of fed and fasted rats has been studied. The perfusion medium contained glucose at a concentration of 300 mg/dl or no glucose. It has been found that glucose has no effect on insulin removal in either group and that fasting had no effect on this process. It is concluded that blood glucose concentration does no influence insulin removal by the liver. PMID- 2226283 TI - Emergency aspects of alcoholism. PMID- 2226284 TI - Alcoholic ketoacidosis. AB - Alcoholic ketoacidosis is characterized by a metabolic acidosis with an elevated anion gap. It generally is seen in the chronic alcoholic patient who has recently gone on a "binge" that was terminated because of complaints such as nausea, vomiting or abdominal pain. Caloric intake is diminished. Treatment includes volume repletion and glucose administration. Morbidity and mortality usually result from intercurrent illness. PMID- 2226285 TI - Electrolyte abnormalities in the alcoholic patient. AB - The acute effect of ethyl alcohol ingestion is to induce diuresis with excretion of free water and preservation of electrolytes. This occurs as the blood alcohol concentration is increasing and is due to the suppression by alcohol of the endogenous release of ADH. During a steady blood alcohol concentration, alcohol acts as an antidiuretic, causing retention of water and electrolytes. While at steady state, additional doses of alcohol will produce progressively smaller and eventually absent diuretic responses. The chronic effect of alcohol is to promote isosmotic retention of water and electrolytes due to increased ADH levels. Excess water and electrolytes are acutely excreted in response to additional alcohol ingestion. With the cessation of alcohol intake, this excess will be excreted over several days. Routine parenteral fluid administration to chronic and withdrawing alcoholics should be avoided. The role of potassium and magnesium in the genesis of specific manifestations of the alcohol withdrawal syndrome is not clear. Alcoholic patients may have electrolyte abnormalities due to alcohol induced diseases, poor nutrition, or vomiting and diarrhea. Each case must be individually evaluated. PMID- 2226286 TI - Cardiac disease in the alcoholic patient. AB - Ethanol in acute low doses is believed to be relatively nontoxic to the normal myocardium, despite data indicating low-level contractility impairment. In patients with myocardial disease, or as the serum ethanol concentration is increased to high levels, angina, myocardial infarction, and arrhythmia may be potentiated. Chronic ethanol use, at moderate doses, may be protective against coronary artery disease, despite increased rates of hypertension. Alcohol consumption at high doses may result in dilated cardiomyopathy and a dismal prognosis. Alcohol abuse is associated with increased mortality. PMID- 2226287 TI - Infections in alcoholic patients. AB - Alcoholic patients have an increased susceptibility to certain bacterial infections. Among the more important of these infections are pneumonia, tuberculosis, spontaneous peritonitis, and bacteremia. This susceptibility is caused by alteration of immune function and mechanical defenses and are the sequel of chronic alcoholism, most notably cirrhosis. In many infections, morbidity is increased in alcoholics, with the course of the illness being more severe and complications more frequent. Assessment of the alcoholic patient with suspected infection should, therefore, be thorough and treatment prompt. PMID- 2226288 TI - Alcohol withdrawal syndromes. AB - Current studies have begun to elucidate the pathophysiology of alcoholism and its withdrawal syndrome. Newer benzodiazepines, beta-blockers, alpha-agonists, butyrophenones and calcium channel blocking agents, alone and in combination, have been studied recently in alcohol withdrawal. This article discusses evaluation and therapy for delirium tremens, major alcohol withdrawal, mild alcohol withdrawal, adjunct therapy, and admission criteria. PMID- 2226289 TI - Seizures in the alcoholic patient. AB - The First International Symposium on Alcohol and Seizures (September 1988, Washington, DC) convened experts from North America and Europe to discuss the basic and clinical research findings in this field. Most of the observations communicated at this symposium are included in this article. Emergency physicians are familiar with the alcoholic patient who presents during or after a seizure(s). This familiarity must not obscure the fact that a significant minority of these patients will have an underlying process that can cause morbidity or mortality if the unsuspecting physician does not have an organized and methodic approach to the evaluation and management of the seizing alcoholic patient. Status epilepticus should be evaluated and treated in a similar fashion, whether or not the patient is an alcoholic. Otherwise, almost without exception, there are nuances and controversies with respect to the evaluation and management of the alcoholic patient with a seizure(s), from the indications for CT scan, to the proper role of sedatives and anticonvulsants, and the need for admission. The emergency physician must remain a patient advocate. The great majority of alcoholic patients with seizures who require admission can be treated satisfactorily at the hospital of presentation. PMID- 2226290 TI - Neurologic complications of alcoholism. AB - Neurologic and myopathic complications of alcoholism are multiple and diverse, affecting both the central and peripheral nervous systems. In the ED, initial concern is for diagnosing readily reversible causes and ruling out possible life- or limb-threatening etiologies. A rapid assessment of the ABCs, a fingerstick blood glucose determination, and, in cases of AMS, the administration of intravenous naloxone is indicated. In almost every instance of a potential neurologic complication, intravenous thiamine replacement is indicated initially, along with the parenteral administration of folic acid and the other B vitamins, including nicotinic acid and pyridoxine. Metabolic screening with electrolytes, glucose, blood urea nitrogen, creatinine, calcium, magnesium, liver enzymes (AST, alkaline phosphatase), bilirubin, arterial blood gases with carboxyhemoglobin determination, and a complete blood count are often warranted. Special tests such as CT scan, CK, ammonia, or toxicologic screens are indicated in specific instances. In terms of physical examination, attention to the presence of focal neurologic findings is paramount because of the possibility of a subdural or epidural hematoma. It is important not to miss meningitis and a low threshold for treatment or lumbar puncture should be maintained. Specialized consultation and referral are needed only after stabilization and appropriate tests are performed. If an organized approach to the evaluation of an alcoholic with neurologic symptoms is undertaken, occult disease will not be missed and outcomes will be improved. PMID- 2226291 TI - Alcohol and gastrointestinal bleeding. AB - Ethanol has experimentally been shown to be "ulcerogenic," independent of gastric intraluminal pH. Ethanol remains ulcerogenic despite antisecretory doses of H2 receptor antagonists. Low-dose alcohol stimulates acid secretion in man, an effect possibly mediated by histamine or gastrin. High-dose alcohol reduces intraluminal acid by damaging mucosa, thereby enhancing back diffusion of hydrogen ion, and also by direct damage to oxyntic (parietal) cells. Ethanol is capable of increasing gastric mucosal permeability as evidenced by the increase in back diffusion (increases intraluminal pH) and by the characteristic fall in transmucosal potential difference which reflects surface cell layer exfoliation. This exfoliation may offer an explanation for the potentiating effect of alcohol on gastric mucosal injury when it is ingested simultaneously with other gastric irritants. Ethanol of greater than 20% concentration can rapidly destroy the gastric mucus-bicarbonate layer, which may be a defense layer for both the inhibition of back diffusion and bicarbonate neutralization of existing acid. Ethanol depletes sulfhydryl compounds in gastric mucosa. These sulfhydryls may be necessary for stabilization of cell membranes as well as for binding free radicals. Ethanol is damaging to the mucosal microcirculation. The rapidity of ethanol-induced damage makes it unlikely that the process is purely ischemic. The cytoprotective phenomenon, as this brief literature review suggests, is a multifactorial, dynamic process. The complex interplay of mucosal defense factors, endogenous and exogenous stimuli, induction of humoral responses, and ultimately the success or failure of cellular repair, is unlikely to be solely mediated by endogenous prostaglandins. Although prostaglandins are unquestionably significant to cytoprotection, the supporting and, perhaps, major roles of leukotrienes, sulfhydryls, histamines, and like substances cannot be ignored. Several innovative therapeutic agents directly derived from these research efforts have already entered the clinician's formulary. The significance of the concept of cytoprotection is only now being realized in clinical applications. Alcoholic hemorrhagic gastritis, although a significant clinical entity, remains a rather elusive diagnosis for the emergency physician. As a diagnosis of suspicion, therapeutic trials of antacids, sucralfate, or perhaps synthetic prostaglandin analogues are acceptable, pending endoscopic verification or short term resolution of symptoms. All patients presenting with true hemorrhage or with persistent symptoms should undergo gastroenterologic referral and endoscopic evaluation. The Mallory-Weiss syndrome has long been associated with acute and chronic alcohol abuse.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2226292 TI - Pancreatitis. AB - Pancreatitis is a common but rather poorly understood entity most often associated with alcohol abuse or biliary tract disease. Despite the availability of a variety of diagnostic tests and imaging techniques, the diagnosis of pancreatitis continues to be primarily a clinical one. Of major concern to the emergency physician is distinguishing pancreatitis from other, potentially lethal, causes of abdominal pain, and identifying those patients with severe pancreatitis who are at risk for a complicated course secondary to the remote systemic effects of the disease. PMID- 2226293 TI - Alcoholic liver disease. AB - Alcoholic liver disease presents a wide spectrum of clinical manifestations ranging from mild asymptomatic fatty liver to alcoholic hepatitis and severe life threatening liver failure with ascites, hemorrhaging esophageal varices, and encephalopathy. Although still poorly understood, the mechanism of this injury is probably the result of numerous direct toxic and metabolic effects of alcohol on the hepatocyte. Therapy consists primarily of abstinence and supportive care. However, several newer treatments are actively being studied. These include prednisolone, anabolic steroids, glucagon and insulin, propylthiouracil, and cyanidanol. Colchicine is promising as an agent to inhibit fibrosis. Complications of cirrhosis, including ascites and variceal hemorrhage, are the result of end stage disease. A return to old techniques of ascitic fluid management suggests that therapeutic large-volume paracentesis with albumin infusion is a safe and effective form of therapy. Variceal hemorrhage is best treated with sclerotherapy, vasoconstrictors, and balloon tamponade. Little has been done to alter the ultimately dismal prognosis and long-term survival of alcoholic liver disease. PMID- 2226294 TI - Alcoholism and society. AB - The problems of alcohol abuse are rampant in society and permeate the Emergency Department experience. The cost to society as measured by social, medical, occupational, and legal effects is exceedingly high and probably underestimated. Emergency physicians have the opportunity to intervene in this vicious cycle and must learn their role in the process. PMID- 2226295 TI - The other alcohols. Methanol, ethylene glycol, and isopropanol. AB - The alcoholic patient, in an attempt to maintain an altered mental status, may ingest ethanol substitutes containing methanol, ethylene glycol, or isopropanol. The subsequent clinical presentation in the Emergency Department is highly variable and depends on the ethanol substitute ingested, the time since ingestion, and concomitant ethanol abuse. This article describes the clinical features of intoxication by the ethanol substitutes. Early diagnosis and therapeutic intervention may prevent irreversible sequelae. The rationale for treatment interventions is discussed. PMID- 2226296 TI - Alcohol and trauma. AB - Countermeasures to alcohol-related trauma are essential. The public perception that there is low risk of detection and punishment for alcohol-precipitated violence is being addressed. Current legislation is aimed at decreasing the availability of alcohol (e.g., adjusting legal drinking age, decreasing the serum alcohol intoxication limit, restricting the sale of alcoholic beverages at public events), increasing detection (e.g., greater driver surveillance, increased number of dedicated personnel), strengthening legal penalties for alcohol-related offenses, and mandating rehabilitative therapy. Physicians can intervene in the alcohol-trauma cycle. Unfortunately, they are notably poor in detecting the patient with alcohol-related injury. Moreover, physicians infrequently refer these patients to facilities and personnel that are expert in alcohol detoxification and rehabilitation. Recidivism can be positively impacted by physicians who are sensitive to and versed in the medical and social patterns of alcohol abuse. PMID- 2226297 TI - RU486 and the early nineties. PMID- 2226298 TI - Sources of cholesterol for testosterone biosynthesis in murine Leydig cells. AB - The sources of cholesterol for testosterone production were investigated in freshly isolated murine Leydig cells. In vitro stimulation with human CG (hCG) (0.2 IU/ml) caused a 75-fold increase in testosterone production. Leydig cells contained approximately equal amounts of free and esterified cholesterol (7.8 vs. 8.7 micrograms/mg protein). The total cholesterol content of cells stimulated for 4 h with hCG was significantly decreased compared with unstimulated cells (8.4 vs. 17.6 micrograms/mg protein); both free and esterified cholesterol decreased by about 50%. In unstimulated Leydig cells incubated with [14C]acetate for 12 h, the majority of incorporated [14C] was found in free and esterified cholesterol, whereas, in the hCG-stimulated cells, 80% of incorporated 14C was in testosterone. The activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase after 4 h in hCG-stimulated cells was 20% higher than in unstimulated cells (115.5 vs. 84.4 pmol/mg protein.min). However, by 6 h, HMG-CoA reductase activity doubled in the hCG-stimulated compared with unstimulated cells. By 12 h, HMG-CoA reductase activity in hCG-stimulated cells was 4 times the preincubation level and 8 times the 12-h level in unstimulated cells. HMG-CoA reductase activity induced by hCG was blocked by aminoglutethimide, an inhibitor of the cholesterol side-chain cleavage enzyme. Lovastatin, a potent inhibitor of HMG-CoA reductase, had no effect on unstimulated or hCG-stimulated testosterone production during a 12-h incubation. Murine high density lipoproteins (mHDL) increased HMG-CoA reductase activity in both unstimulated (29%) and hCG stimulated (20%) cells. During a 6 h incubation, mHDL increased hCG-stimulated testosterone production by 20%, but had no effect on unstimulated testosterone production. These results suggest that murine Leydig cells store enough cholesterol and cholesteryl esters to support testosterone production for at least 12 h in vitro. Although mHDL does not have a major stimulatory effect on testosterone biosynthesis, it may be involved in the regulation of de novo cholesterol synthesis. PMID- 2226299 TI - Anionic complex-carbohydrate units of human thyroglobulin. AB - Human thyroglobulin (hTG) contains sulfate in chondroitin 6-sulfate chains and in complex carbohydrates. In this study the sulfate-containing complex carbohydrates were characterized by the number of sulfate and sialic acid residues that they contain. Samples of normal and nodular thyroid tissue were incubated for 16 h in [35S]sulfate-containing medium, and hTG was purified from the tissues and the media. Complex carbohydrates were enzymatically removed from hTG. Subsequent analysis on an HPLC anion exchange column at pH 2.2 separated the carbohydrate units according to their number of negative charges. Sulfate-containing peaks were monitored by radioactivity, and sialic acid-containing peaks were identified by their shift to lower charge after treatment with neuraminidase. Peaks corresponding to sialic acid-free carbohydrate units with one to four sulfates were identified. Also, carbohydrate units with two and three negative charges containing both sulfate and sialic acid were present. In the nodular tissue of one patient there were more sulfated units with higher charge, especially units containing sialic acid. In this patient the proportion of sulfated polyvalent units with sialic acid was 22.4% for normal and 64.6% for nodular tissue. No difference in the composition of the charged units between the tissues and their corresponding media was seen, making it unlikely that the sulfate-containing carbohydrates play a role in hTG release. It is concluded that hTG contains complex carbohydrate units with up to four sulfate groups and units with both sulfate and sialic acid. In some patients, the sulfate-containing anionic carbohydrate units of hTG from normal and nodular thyroid tissue are different. PMID- 2226300 TI - Insulin-like growth factor II is a potent inhibitor of the aromatase activity of human placental cytotrophoblasts. AB - The placenta is the primary source of estrogens and progesterone during pregnancy. Because pregnant diabetic women are reported to have lower serum estrogen and higher progesterone levels than nondiabetic pregnant women, and placental insulin-like growth factor II (IGF-II) production may be elevated during diabetic pregnancy, the role of IGF-II in the regulation of human cytotrophoblastic aromatase, 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), and P450 cholesterol side-chain cleavage (P450scc) enzyme activities was studied. Incubation of cytotrophoblasts with IGF-II for 24 h significantly diminished the ability of these cells to convert androstenedione to estrogens by 92.3 +/- 6.6 (SE)%. IGF-II could suppress aromatase activity at a concentration as low as 2.0 ng/ml. Preincubation of cells with either insulin, IGF-I, or a monoclonal anti IGF-I receptor antibody did not alter IGF-II's potent inhibitory effect. Treatment with mannose 6-phosphate alone also resulted in significant suppression of aromatase activity, and concurrent treatment with both mannose 6-phosphate and IGF-II resulted in greater inhibition than with either agent alone. These observations suggest that IGF-II suppresses aromatase activity by activation of its own specific receptor. In contrast, incubation of cytotrophoblasts with IGF II for 24 h significantly increased the 3 beta HSD activity (as determined by the conversion of pregnenolone to progesterone) and P450scc activity (as determined by the conversion of 25-hydroxycholesterol to progesterone) of these cells. IGF II's ability to stimulate these enzymatic processes was found to be comparable in magnitude to that of IGF-I. IGF-II-stimulated 3 beta HSD activity was completely inhibited by concurrent treatment with either actinomycin D or cycloheximide, suggesting that new mRNA and protein synthesis are required for IGF-II to exert its stimulatory effect. These studies indicate that IGF-II is a potent inhibitor of human cytotrophoblastic aromatase activity in vitro. In addition, IGF-II can stimulate cytotrophoblastic 3 beta HSD and P450scc activities. Since placental IGF-II production in pregnant diabetic women may be augmented, these observations may help explain the lower serum estrogen and higher progesterone levels associated with pregnancy in the diabetic patient. PMID- 2226301 TI - Suckling increases the proportions of mammotropes responsive to various prolactin releasing stimuli. AB - It is well established that the suckling stimulus sensitizes or primes the anterior pituitary to PRL-releasing stimuli. It is also recognized that PRL secreting cells from a given animal are not all alike but instead exhibit a considerable degree of functional heterogeneity. The goal of the present study was to determine whether the suckling-induced priming phenomenon is manifest at the cellular level by shifts in the relative abundance of various mammotrope subpopulations. This was accomplished by using reverse hemolytic plaque assays to evaluate the secretory characteristics of individual PRL secretors derived from lactating rats either before or after the transient application of a suckling stimulus. Groups of day 10 lactating rats separated from their litters for 4 h were either killed immediately or were reunited briefly (10 min) with their pups before death. Adenohypophyseal cells obtained after trypsin dispersion were then subjected to plaque assays for PRL. Mammotropes derived from suckled rats were, on average, considerably more responsive to the stimulatory actions of TRH and angiotensin II and less susceptible to inhibition by dopamine. Mammotropes from nonsuckled rats exhibited a bimodal frequency distribution in which plaques from the second mode were roughly 6-8 times larger (released considerably more PRL) than those from the first. Superimposition of suckling (or in vitro treatment with dopamine) caused the second mode to disappear. Suckling also enhanced greatly the fraction of PRL cells that shifted from the first to the second mode (i.e. released more hormone) after treatment with TRH or angiotensin II. Taken together, our results demonstrate that the suckling-induced sensitization of pituitary tissue to PRL-releasing stimuli is manifest at the cellular level as proportional shifts toward those cells most responsive to stimulatory secretagogues and away from those most susceptible to inhibition by dopamine. PMID- 2226302 TI - Arginine vasopressin and corticotropin releasing factor: binding to ovine anterior pituitary membranes. AB - In the sheep, in contrast to the rat, arginine vasopressin (AVP) is a more potent stimulus to ACTH secretion from the anterior pituitary (AP) than CRF. To further explore this difference, we have compared [3H]AVP and [125I]-[Nle21 Tyr32]ovine CRF binding in membranes prepared from rat and sheep AP. Between species, no difference in affinity of binding was found for either ligand. In contrast, the concentration of AVP receptors in sheep AP was twice that in rat, whereas that of CRF receptors was only one tenth. AVP receptor concentration in sheep AP was not altered by chronic (10 day) dexamethasone administration, but fell to 60% of control after chronic (60 day) hypothalamo-pituitary-disconnection. The increased level of AVP receptors and the much lower level of CRF receptors in sheep compared with rat may thus provide an explanation for our previous findings of increased sensitivity to AVP and a very poor response to CRF in stimulating ACTH release from the sheep AP. In addition the finding that AVP receptor numbers are reduced in the hypothalamo-pituitary-disconnected sheep suggests that hypothalamic factors may play a role in regulating AVP receptor concentration in the ovine AP gland. PMID- 2226303 TI - Monoclonal antibodies against luteinizing hormone receptor. Immunochemical characterization of the receptor. AB - Human CG (hCG)-receptor complexes were solubilized from porcine testicular membranes. They were chromatographed on an immunomatrix of Affi-Gel 10-D1E8 anti beta-hCG monoclonal antibody (this antibody has been shown not to interfere with hCG binding to receptor). Elution was performed at alkaline pH, a condition in which hCG-receptor complexes are relatively stable. Immunization of a mouse with these partially (approximately 15%) purified hormone-receptor complexes allowed the preparation of 20 different hybridomas, each secreting antireceptor antibodies. The latter were used for receptor characterization. Immunoblot of testicular membrane extracts or of purified receptor preparations showed the presence of a major band at approximately 85,000 mol wt and minor bands at approximately 68,000 mol wt and approximately 48-45,000 mol wt. The width of all these bands suggested some microheterogeneity possibly due to glycosylation. The same approximately 85,000 mol wt receptor was seen in ovarian membranes, but no detectable antigen was observed in liver, muscle, and kidney membranes. An immunoaffinity method (using antibody LHR 38) was devised to purify the receptor in a single step. This demonstrated that the purified receptor preparation did not contain any protein component other than those detected by immunoblot. Comparison of receptors purified by immunoaffinity chromatography using either antireceptor or antihormone monoclonal antibodies showed in both cases the presence of the 85,000 mol wt and 48-45,000 mol wt species, but the absence, in the latter case, of the 68,000 mol wt species. This suggests that the 68,000 mol wt receptor cannot bind hormone and does not form oligomers with other receptor species. PMID- 2226304 TI - Intercellular propagation of individually programmed growth bursts in FRTL-5 cells. Implications for interpreting growth factor actions. AB - Five methods are commonly used to quantify FRTL-5 cells' and other thyrocytes' growth in vitro and the impact of growth inhibiting or stimulating maneuvers: Total cell count, mitotic index, DNA measurement, total [3H]thymidine incorporation, and the fraction of [3H]thymidine labeled cells. All of them assess cell growth as though all cells were homogeneous with an identical response to growth factors. We demonstrate here that this assumption is not valid. Rather, some intrinsically growth-prone cells appear to pass a growth signal to neighboring cells so that variably sized colonies of synchronized cells within each cluster growing from monodispersed cells are formed. This is true for FRTL-5 cells growing in vitro in monolayers and in three-dimensional, collagen embedded spheroids. The pattern is the same when cell suspensions or collagen embedded spheroids are implanted onto nude mice. Patches with alternating high and low growth become particularly prominent in the large tumor-like organoids grown from monodispersed cells in nude mice. The pattern much reminds of similar observations in growing intact thyroids. Since there is no significant correlation between the fraction of [3H]thymidine labeled cells and the size of two- or three-dimensional clusters in any experiment, growth of signal-spreading cells is assumed to occur in leaps and bounds. Growth velocity in each subclone of a cell population depends on the mean interval between bursts of replications and on the number of cells synchronized by cell-to-cell diffusion of the growth signal emanating from one dividing cell. Thus, growth-promoting and growth inhibiting factors may not only act on the mean interval between successive growth bursts, but they may also change cell-to-cell spreading of growth signals. PMID- 2226305 TI - Expression of the pregnancy-specific beta 1-glycoprotein gene in cultured human trophoblasts. AB - Human pregnancy-specific beta 1-glycoprotein (PS beta G), the major placental glycoprotein, shares strong sequence similarity with carcinoembryonic antigen and is a member of the immunoglobulin superfamily. To understand the role of PS beta G in placental ontogeny during pregnancy, we examined its synthesis and regulation in primary cultures of trophoblast cells. Freshly plated (12 h) cytotrophoblasts expressed little PS beta G transcripts; however, within 24 h of culture, PS beta G mRNAs became detectable. PS beta G synthesis and mRNA expression increased with time in culture, and maximal synthesis was achieved at 4 days, indicating that primary trophoblasts continue differentiating in vitro. Molecular cloning revealed that PS beta G is an extremely polymorphic protein. Most PS beta G cDNAs identified to date, including the three cDNAs (PSG16, PSG93, and PSG95) isolated in this laboratory, share strong sequence similarity in the 5' (designated PSG-5') and coding regions, but differ in sequences at the 3' region. The PSG-5', PSG93-specific, PSG16/PSG93-3', and PSG95-3' probes, which identify the majority of PS beta G mRNAs, hybridized with three mRNAs of 2.3, 2.2, and 1.7 kilobases in primary trophoblasts and human term placental tissue. Ribonuclease protection analysis demonstrated that primary trophoblasts expressed most of the placental PS beta G transcripts. However, culturing in vitro altered PS beta G gene expression, and the level of PS beta G transcripts containing a PSG95-3' sequence was preferentially increased in primary trophoblasts. Moreover, primary trophoblasts synthesized a 64K PS beta G polypeptide in variable amounts and three PS beta Gs of 72K, 62K, and 54K in roughly equal amounts, whereas purified human term placental PS beta G consists of a major polypeptide of 72K and two minor ones of 64K and 54K. PS beta G gene expression in primary trophoblasts was slightly reduced by 8-bromo-cAMP, but was markedly inhibited by sodium butyrate. PMID- 2226306 TI - Changes in 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase messenger ribonucleic acid, activity and protein levels during the estrous cycle in the bovine ovary. AB - A 1169 base pair fragment of bovine 3 beta-hydroxysteroid dehydrogenase/delta 5 delta 4 isomerase (3 beta-HSD) cDNA was used to quantitate 3 beta-HSD messenger RNA (mRNA) levels in the bovine ovary during the estrous cycle. The content of 3 beta-HSD protein was measured by immunoblot analysis using an antiserum developed in rabbits against human 3 beta-HSD, whereas 3 beta-HSD activity was measured using [3H]pregnenolone, [3H] dehydroepiandrosterone, and [3H]androst-5-ene-3 beta,17 beta-diol as substrates. There was a parallel increase in 3 beta-HSD mRNA, protein content, and enzymatic activity levels from days 1-3 after estrus to maximal values at 50-100% above control on days 8-11 after estrus. Thereafter, all values decreased progressively until days 16-17 before a dramatic fall to 5% or less than maximal values on days 18-20 after estrus. Almost superimposable results of enzymatic activity were obtained with the three substrates, thus suggesting a unique 3 beta-HSD or parallel changes in the activity of multiple 3 beta-HSDs. The above-described changes observed during the luteal phase are almost exclusively due to variations in corpora lutea. In fact, 3 beta-HSD activity in ovarian follicles was approximately 10,000 lower than that measured in corpora lutea. The close correlation observed over a wide range of 3 beta-HSD mRNA, protein content, and activity levels suggests that changes of ovarian 3 beta-HSD activity are controlled at the level of 3 beta-HSD gene expression and/or 3 beta-HSD mRNA stability. PMID- 2226307 TI - Tissue distribution and molecular heterogeneity of human growth hormone-releasing factor in the transgenic mouse. AB - Transgenic mice expressing the human growth hormone-releasing factor (hGRF) gene linked to the metallothionein promoter exhibit high circulating levels of hGRF and GH and increased growth. We have described the distribution of GRF immunoreactivity (GRF-IR) in various tissues and characterized its molecular heterogeneity using gel filtration and high performance liquid chromatography (HPLC) and two separate RIAs that recognized mid-molecule and carboxyl-terminal epitopes of hGRF. The highest levels of GRF-IR were in the pituitary, followed by the pancreas. Intermediate levels were present in hypothalamus and liver, and lower levels in visceral organs, heart, and gonads. The pituitary and brain revealed evidence of the two mature hormone forms [hGRF(1-44)-NH2 and hGRF(1-40) OH and in addition a more hydrophobic form that is believed to represent the hGRF precursor (proGRF) on the basis of its estimated molecular size (approximately 9,000) and selective recognition by the mid-molecule RIA. The profiles of GRF in pancreas and gut were similar except that only minimal amounts of hGRF(1-40)-OH were detected. In contrast, neither mature hormonal form was present in the liver and plasma contained primarily hGRF(3-44)-NH2, the major circulating metabolite of hGRF. The results provide evidence for variable processing of the hGRF precursor that is tissue specific and indicate that several extrahypothalamic tissues possess the necessary complement of enzymes to generate the mature hormonal forms. PMID- 2226308 TI - Inhibitory effects of a tumor-promoting phorbol ester on luteinizing hormone stimulated renin and prorenin production by cultured bovine theca cells. AB - In this report, we have described a serum free culture method for culturing bovine theca cells in vitro. These cultured cells could be stimulated with LH to produce renin and prorenin. Though intracellular prorenin as well as renin was increased by LH, no renin was found to be released into the extracellular medium. The extracellular medium contained prorenin exclusively. The stimulatory effect of LH could be mimicked by 8-bromo-cAMP (8-Br-cAMP) and forskolin, suggesting cAMP to be the second messenger involved. Induction of renin and prorenin production by LH in cultured theca cells was dependent upon de novo protein synthesis, since the action of LH could be completely blocked by the protein synthesis inhibitor, cycloheximide. The stimulatory effects of LH, 8-Br-cAMP, or forskolin were also blocked by 4 beta-phorbol 12-myristate 13-acetate (PMA), via putative activation of protein kinase C. However, to completely block the stimulatory effect of LH or 8-Br-cAMP, it was necessary to add PMA either before LH/8-Br-cAMP was added or simultaneously with the agonists. With progressive delay in addition of PMA after LH/8-Br-cAMP was added, the extent of inhibition decreased gradually and if PMA was added anytime after 4 h of LH/8-Br-cAMP addition, no inhibitory effect could be observed. Thus we have shown that renin/prorenin production by theca cells in vitro can be directly regulated by LH in a cAMP-dependent manner. Prorenin is preferentially released from the cells. Activation of protein kinase C appears to inhibit some very early steps in the induction of prorenin/renin production which however is distal to cAMP formation. PMID- 2226309 TI - Progesterone action in normal mouse mammary gland. AB - Previously it has been shown that progesterone, as well as estrogen, plays an important role in the growth of the mammary gland. Eighty percent of mammary progesterone receptors (PgR) are estrogen-inducible and are localized in the epithelium; the remaining 20% of PgR are estrogen-independent and appear to be localized in the mammary stroma. The purpose of the present study was to investigate how progestins promote mammary growth in relation to their interactions with epithelial and stromal components of the gland and to assess the role of estrogen in these interactions. Progestins [progesterone, [17 beta methyl-3H]promogestone (R5020), and medroxy progesterone acetate] alone or in combination with estrogen were combined with Elvax 40P and implanted directly into mammary glands. The effect of hormones on cell proliferation was determined by observing changes in mammary gland morphology and by quantitating DNA synthesis in both epithelial and stromal cells by DNA histoautoradiography. The results demonstrate that in mammary epithelial cells the effects of progestins on mammary gland morphology and DNA synthesis are locally mediated such that proliferative changes in the hormone-implanted glands were greater than in contralateral control glands. Dose-response studies with estrogen and R5020 revealed that the extent of progestin activity was only partially dependent upon the R5020 dose with the major determining factor being the dose of estrogen. Analysis of the effect of estrogen on mammary PgR concentration indicates that the degree and pattern of the morphological response of ductal sidebranching and increases in DNA synthesis are largely due to the increase in estrogen-dependent PgR. The antiprogestin, 11 beta-(4-dimethylamino-phenyl)1-17 beta-hydroxy-17 alpha-(prop-1ynyl)-estra-4,9-diene-3-one (RU486), blocks the proliferation in the epithelium that is mediated through estrogen-dependent PgR. In contrast, in stromal cells progestin activity is not estrogen-dependent, and stimulation of DNA synthesis was not confined to the hormone-implanted glands. Furthermore, RU486 stimulates stromal cell DNA synthesis, and this response is augmented by estrogen. While progestin effects in epithelial cells appear to be mediated by estrogen-dependent PgR, the mechanism operative in stromal cells appears to be different and remains to be elucidated. PMID- 2226310 TI - Developmental and tissue-specific regulation of proglucagon gene expression. AB - The pattern of glucagon gene expression and the posttranslational processing of proglucagon was studied in the fetal and neonatal rat. Pancreatic immunoreactive glucagon (IRG) and glucagon-like immunoreactivity (GLI) were low in both fetal pancreas and intestine, respectively. Immediately after birth, pancreatic IRG rose markedly and reached a peak concentration at postnatal day 7, followed by a gradual return to its adult level. Intestinal GLI was low until postnatal day 7 and rose steadily thereafter to adult levels. The levels of GLI in the hypothalamus were much lower than in intestine, yet the developmental accumulation of hypothalamic GLI resembled the pattern observed in intestine. In contrast, the levels of GLI and IRG in the brain stem were higher in the fetus and neonate, and decreased to adult levels. Proglucagon mRNA transcripts, uniform in size, were detected in RNA isolated from fetal or adult brainstem, pancreas, and intestine. However, fetal proglucagon mRNA transcripts were larger than adult proglucagon mRNA transcripts in pancreas and intestine, but not brainstem. The results of RNAse mapping studies, including analysis of both the 5'- and 3'-ends of the mRNA transcripts, demonstrated that the larger fetal mRNA transcripts could be accounted for by an increase in the length of the polyadenylate tail in the fetal tissues. These observations demonstrate that the developing rat exhibits tissue-specific differences in both proglucagon gene expression and the pattern of posttranslational processing of the prohormone. PMID- 2226311 TI - Altered glucagon- and catecholamine hormone-sensitive adenylyl cyclase responsiveness in rat liver membranes induced by manipulation of dietary fatty acid intake. AB - Glucagon-stimulated adenylyl cyclase activity has been shown to change in liver membranes manipulated to alter either their fatty acid composition or fluidity. We examined whether membrane alterations induced by dietary manipulation affected receptor function. Glucagon- and beta-adrenergic-stimulated receptor-adenylyl cyclase systems were examined in liver membranes of rats fed diets containing 10% corn oil, 10% coconut oil (essential FFA deficient), or 8.5% coconut oil with 1.5% corn oil (essential FFA repleat). Basal and maximal nonreceptor-mediated adenylyl cyclase activity (stimulated by NaF, guanylylimidodiphosphate, and forskolin) was the same in membranes of each of the dietary groups, suggesting that Gs-protein and the catalytic unit activity per se were unaltered by the manipulations. Glucagon-stimulated adenylyl cyclase activity increased with increasing unsaturation of dietary fatty acids; activity in coconut oil-fed rats was 527 +/- 30 (mean +/- SEM) pmol/mg.10 min, that in coconut/corn oil-fed rats was 752 +/- 74 pmol/mg.10 min, and that in corn oil-fed rats was 981 +/- 94 pmol cAMP/mg.10 min. [125I]Monoiodoglucagon binding did not increase in parallel to the adenylyl cyclase alterations; coconut oil-fed animals (614 fmol/mg) differed from the other groups (450 and 430 fmol/mg). Isoproterenol (beta-adrenergic) stimulated adenylyl cyclase activity was also highest in the corn oil-fed animals, but was similar in the other dietary groups, with no difference in other characteristics of [125I]iodopindolol binding between the groups. The results demonstrate that alterations in the glucagon-stimulated adenylyl cyclase response are different from those in the beta-adrenergic adenylyl cyclase response. Further, they suggest that although direct activations of the catalytic unit or its interaction with the guanine nucleotide-sensitive protein are apparently not affected, hormone receptor-mediated adenylyl cyclase activity may be altered by these dietary manipulations. PMID- 2226312 TI - Localization of the thyroxine binding sites in apolipoprotein B-100 of human low density lipoproteins. AB - By photoaffinity labeling human low density lipoproteins (LDL) with [125I]T4 we confirmed our previous observation that of the three T4 binding sites of apolipoprotein B-100 (apoB-100) one is in its 26% NH2-terminal portion [apoB-26, the 140 kDa fragment, residues 1-1297] and two in the remaining 74% COOH portion (apoB-74, 410 kDa, residues 1298-4536). We now show that of these two sites one is in the NH2 portion of apoB-74 (apoB-44, 240 kDa, residues 1298-3249) and the other in the nonoverlapping COOH portion (apoB-30, 170 kDa, residues 3250-4536). ApoB-100 contains 13 binding sites for heparin, a known inhibitor of T4 binding to the major T4 carrier plasma proteins; however, heparin failed to inhibit T4 binding to apoB-100 and fragments thereof. The same failure was seen with three monoclonal antibodies (MAbs), 4G3, 5E11, and 43 that block totally or partially LDL binding to the LDL receptor [respective epitopes at residues 2980-3084 (apoB 44), 3441-3569, and 4027-4081 (apoB-30)]. Of the other 3 MAbs, all without effect on LDL binding to the LDL receptor, [1D1, 2D8, and 16, respective epitopes at residues 474-539 (apoB-26), 1438-1481 (apoB-44), and 4154-4189 (apoB-30)], only two (MAbs 1D1 and 2D8) inhibited T4 binding (21 to 39%). We conclude that the three T4-binding sites of apoB-100 are outside the LDL receptor binding domain, distant from the heparin binding sites and, assuming no allosteric effects, in the vicinity of residues 474-539 (T4 site of apoB-26), 1438-1481 (T4 site of apoB 44), and in the C terminal quarter of apoB-30. PMID- 2226313 TI - Small intestinal fatty acid synthesis is increased in diabetic rats. AB - Several studies have demonstrated that intestinal triglyceride production and secretion are increased in diabetic animals and may contribute to the hypertriglyceridemia that accompanies diabetes. There are three potential sources of fatty acids for intestinally derived triglycerides; de novo fatty acid synthesis, circulating free fatty acids, or dietarily derived fatty acids. Prior data have demonstrated that de novo cholesterol synthesis is increased in the small intestine of diabetic animals. The primary aim of the present study was to determine the effect of diabetes on small intestinal de novo fatty acid synthesis. We found that de novo fatty acid synthesis in the small intestine is increased approximately 2-fold in streptozotocin-induced diabetic rats. In contrast, hepatic fatty acid synthesis is decreased in the diabetic animals. The increase in intestinal fatty acid synthesis is observed in both the fed and fasting states. Limiting food intake by pair feeding prevents the diabetic induced increase in small intestinal fatty acid synthesis, a finding similar to previous data on cholesterol synthesis. Thus, the increase in both small intestinal cholesterol and fatty acid synthesis is dependent on the increased food intake that accompanies poorly controlled diabetes. The present study indicates that increases in small intestinal de novo fatty acid synthesis in diabetic animals could play an important role in providing fatty acids for increased small intestinal triglyceride synthesis and secretion. PMID- 2226314 TI - Nongenomic activation of the calcium message system by vitamin D metabolites in osteoblast-like cells. AB - 1,25-dihydroxycholecalciferol (1,25(OH)2D3) rapidly affects calcium (Ca2+) transport in several cell systems, suggesting physiological actions independent of genomic activation. To test this hypothesis, we studied immediate to early effects (0.5-300 sec) of 1,25(OH)2D3 on cytosolic Ca2+ [Ca2+]i in single osteogenic sarcoma ROS 17/2.8 cells loaded with fura-2. An acute rise in [Ca2+]i was observed in 40% of the cells following addition of 1,25(OH)2D3, with a threshold concentration of 10(-11) M. In most cases, the [Ca2+]i rise was transient, with return to baseline within 1 min; less frequently a more prolonged effect was observed, with variable recovery times. 25-hydroxycholecalciferol (25(OH)D3) reproduced the effect of 1,25(OH)2D3 on [Ca2+]i, with equal potency and similar responses, whereas 24,25-dihydroxycholecalciferol, 1 alpha hydroxycholecalciferol, and 22 oxa-1,25(OH)2D3 were not effective. 1,25(OH)2D3 also increased [Ca2+]i in ROS 24/1 cells, which are defective of receptors for the vitamin D metabolites. At high doses (10(-8)-10(-7) M) of 1,25(OH)2D3 the [Ca2+]i rise in ROS 17/2.8 cells was due to both influx of extracellular Ca2+ and release of Ca2+ from intracellular stores, as the effect was only partially inhibited by Ca2(+)-channel blockade by nifedipine. At low doses (10(-9)-10(-10) M), the effect was entirely dependent on extracellular Ca2+. 1,25(OH)2D3 also increased the production of inositol 1,4,5 trisphosphate (Ins(1, 4, 5)P3) and diacylglycerol, at a threshold dose of 10(-9) M, indicating activation of phospholipase C (PLC). In two thirds of the cells studied, a second addition of 1,25(OH)2D3 within 5 min to cells prestimulated with equimolar doses of the vitamin D metabolite resulted in a [Ca2+]i transient of higher amplitude than the first, a phenomenon occurring at all doses of the hormone, and associated with production of Ins(1, 4, 5)P3. This response amplification was not produced by 25(OH)D3, and pretreatment with 1 alpha(OH)D3 did not significantly enhance 1,25(OH)2D3-induced production of Ins(1, 4, 5)P3. In conclusion, activation of the Ca2+ message system by vitamin D metabolites is a rapid, nongenomic effect; 1,25(OH)2D3 specifically activates both PLC and dihydropyridine-sensitive Ca2+ channels, and "primes" the cells to respond with an enhanced [Ca2+]i rise to a subsequent homologous stimulation; the presence of both the 1 alpha and 25 hydroxyl groups is necessary to express the full hormonal action of vitamin D on [Ca2+]i. PMID- 2226316 TI - Functional heterogeneity in neuropeptide-Y-producing cells in the rat brain as revealed by testosterone action. AB - Despite the widespread distribution of neuropeptide-Y (NPY) in various hypothalamic sites, castration reduced and testosterone (T) replacement restored NPY levels selectively in the median eminence (ME), arcuate nucleus (ARC), and ventromedial nucleus (VMN). Since androgen-concentrating cells and NPY-producing cells display overlapping distribution in the ARC and brain stem (BS), we assessed the participation of BS NPY cells in the steroid-dependent site-specific effects on NPY levels. The BS projections to the hypothalamus were severed by bilateral neural transection (BNT) with a knife lowered on either side of the sagittal sinus to the depth of the dorsal tegmentum in the mesencephalon in intact, castrated, or castrated rats that additionally received sc T implants to maintain physiological T levels. Two weeks later, NPY concentrations in microdissected hypothalamic sites and serum LH and T levels were quantitated by RIA. Castration decreased and T replacement increased NPY concentrations in only three sites, such as the VMN, ARC, and ME. In response to BNT in gonadally intact rats, a different site-specific response of NPY levels was observed; NPY levels decreased in the ME, as seen after castration, and, additionally, decreased in the medial preoptic area, paraventricular nucleus, and dorsomedial nucleus, suggesting that BS NPY neurons innervate these four sites. When castration and BNT were performed simultaneously, a combined regional response was evident. NPY levels decreased in six sites, including two sites (ARC and VMN) that normally respond to castration alone, three sites (medial preoptic area, paraventricular nucleus, and dorsomedial nucleus) that normally respond to BNT alone, and the ME, the only site that showed reduction of NPY levels of similar magnitude after either castration or BNT, but the response of combined surgery was not additive. This observation suggested that gonadal steroids act outside the hypothalamus to raise ME NPY levels, and therefore, BNT in intact rats impaired the effectiveness of steroids. To test this hypothesis, the effects of physiological T replacement in the castrate plus BNT group were studied. We observed that whereas T replacement readily raised NPY levels in the VMN and ARC, it was completely ineffective in the third T-dependent site, the ME. Collectively, these findings revealed a functional heterogeneity among NPY-producing cells in response to T. Apparently, there are two distinct neural sites in the rat brain where T acts to exert a site-specific stimulatory effect on NPY in the hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2226315 TI - Effect of thyroxine administration on the expression of epidermal growth factor in the kidney and submandibular gland of neonatal mice. An immunocytochemical and in situ hybridization study. AB - The effect of T4 administration on epidermal growth factor (EGF) expression in kidney and submandibular glands (SMG) was studied in newborn mice. EGF messenger RNA (mRNA) abundance and EGF immunoreactivity were assessed by in situ hybridization and immunohistochemical techniques, respectively. T4 treatment on days 0-6 augmented both the in situ hybridization and immunocytochemical signals in kidney but not in SMG on day 7. By contrast, T4 injections on days 7-14 did not alter the in situ hybridization or immunocytochemical signals in kidney but increased both signals in SMG on day 15. Thus, neonatal T4 treatment augments the levels of EGF mRNA as well as EGF immunoreactivity in both kidney and SMG. The T4 effect is manifested during the first week in kidney whereas the SMG responds to T4 treatment only during the second week of life. PMID- 2226317 TI - Cell surface vitamin D-binding protein (GC-globulin) is acquired from plasma. AB - Vitamin D-binding protein (DBP) is an abundant plasma protein. The observation of immunodetectable, cell-associated DBP on peripheral blood mononuclear cells and placental cytotrophoblasts had presented the question of the origin, function, and precise subcellular localization of cell-associated DBP. Using anti-human DBP F(ab')2 with fluorescence-activated cytometric analysis and immunogold electron microscopy, we detected DBP on the plasmalemma of U937 cells, a monoblastic, histiocytic cell line grown in media supplemented with fetal calf serum (FCS). DBP was then removed from FCS by actin affinity chromatography followed by anti DBP immunoaffinity chromatography. U937 cells in this DBP-free medium exhibited nearly identical growth rates to cells grown in medium containing native FCS. However, in contrast to cells grown with native FCS, those grown for seven to eight generations with DBP-free FCS exhibited less cell-surface DBP as quantified by fluorescence-activated cytometric analysis (73% decrease) and immunoelectron microscopy (88% decrease). DBP mRNA could not be detected in U937 cells, placental tissues, freshly prepared resting and stimulated B and T lymphocytes, or lymphocyte-derived cell lines by Northern analysis. In addition, using the sensitive reverse transcriptase/polymerase chain reaction assay no DBP fragments were detectable in U937 cells. We conclude that U937 cell-associated DBP is exogenously derived from plasma and is located on the plasmalemma. Based upon this conclusion, we postulate that specific binding sites for DBP may exist on the plasma membranes of certain cell types. PMID- 2226318 TI - Prolonged effects of recombinant human interleukin-1 alpha on mouse thyroid function. AB - Rapid and prolonged effects of recombinant human interleukin-1 alpha (IL-1 alpha) on mouse thyroid were studied. After daily administration of 15 micrograms or 1 microgram IL-1 for 7 consecutive days, serum T4 concentrations rapidly fell to undetectable levels but returned to near control level after the cessation of IL 1. On the 31st day, 3 weeks after the drug cessation, a significant depression of serum T4 was observed again. In addition, the IL-1-treated mouse thyroid showed an in vitro unresponsiveness to TSH, with an increase of pituitary TSH (2.24-fold by 15 micrograms IL-1). To understand underlying mechanisms further, serial observations were performed. Thyroidal T4 contents increased initially, decreased to a low level at day 14, and returned to approximately the control level. IL-1 administration induced an increase in the basal thyroidal cAMP level for a prolonged period. Its response to TSH showed a gradual decline to a level approximately 30% of the control by the 31st day. Pituitary TSH contents on the 22nd and 31st days showed significant elevations. Slight decreases in thyroidal TSH binding and T4 contents also were seen concomitantly. These studies indicate that an administration of a large dose of IL-1 results in a dramatic decrease in serum T4 primarily through the inhibition of T4 release from the thyroid. The results also indicate the induction of a prolonged hypothyroid state due to the unresponsiveness to TSH via a postreceptor mechanism. PMID- 2226319 TI - Effect of bilateral splanchnic nerve section on adrenal function in the ovine fetus. AB - The effect of bilateral splanchnic nerve (SPLX) section in fetal sheep [116-121 days gestational age (dGA)] on subsequent adrenocortical function was investigated. Fetal cortisol release was stimulated by 1) ACTH-(1-24) administration (100 ng/min for 15 min) at 126-129 and at 132-135 dGA, and 2) nitroprusside-induced hypotension (50% reduction in fetal arterial blood pressure for 10 min) at 129-132 and 136-139 dGA. No differences were observed between SPLX and control fetuses (CONT) in basal arterial plasma concentrations of cortisol from 126-141 dGA. A significant effect of fetal age on basal cortisol was observed in both SPLX and CONT fetuses from 126-141 dGA. A significant (P less than or equal to 0.05) increase in fetal arterial concentrations of cortisol was achieved by ACTH-(1-24) infusion in SPLX and CONT and did not differ between groups at either 126-129 or 132-135 dGA. Hypotension induced a significant increase in fetal plasma cortisol concentrations in SPLX and CONT fetuses (P less than or equal to 0.05). SPLX fetuses secreted significantly less cortisol in response to hypotension than CONT fetuses at both 129-132 and 136-139 dGA (P less than 0.05). Fetal arterial plasma concentrations of immunoreactive ACTH in response to hypotension were not different between CONT and SPLX fetuses. We estimated the half-life of endogenous fetal plasma cortisol after both hypotension and infusion of ACTH-(1-24). There were no differences between either method of inducing cortisol release on the endogenous cortisol half-life, nor were any differences in cortisol half-life observed between SPLX and CONT. At 136 139 dGA the adrenomedullary response to hypotension was abolished in SPLX, confirming completeness of denervation. In conclusion, the splanchnic nerves do not appear to be involved in the normal increase in basal fetal plasma cortisol observed in late gestation in fetal sheep. However, splanchnic nerve modulation of secretion of cortisol in response to stress may be involved in the increased fetal adrenal sensitivity to stress observed late in gestation. PMID- 2226320 TI - Localization and growth hormone (GH)-releasing activity of rat testicular GH releasing hormone-like peptide. AB - The testis contains many peptides originally described as originating in the central nervous system. The physiological function of these factors in the testis is generally unknown. We previously reported that the rat testis contains both a peptide with GH-releasing hormone-like immunoactivity (tGHRH-LI) and a mRNA species that cross-hybridizes with a hypothalamic cDNA for rat GHRH (rGHRH). The current study was designed to further characterize tGHRH-LI by determining its location within rat testis, and to evaluate whether tGHRH-LI and hypothalamic GHRH share similar biological and electrophoretic properties. Partially purified tGHRH is capable of stimulating GH secretion from cultured anterior pituitary cells in a dose-dependent manner. Testicular GHRH and rGHRH have different HPLC retention times and significantly different electrophoretic properties by Western gel analysis. The estimated size of tGHRH-LI is approximately 3.7 times that of synthetic rGHRH. Using immunohistochemistry, tGHRH-LI is localized to mature sperm forms in rat testis. We conclude that rat tGHRH-LI and rGHRH share some structural and functional properties and are probably related peptides. However, the difference in electrophoretic mobility and HPLC retention time indicates that they are not identical. The presence of tGHRH-LI in rat sperm, within the confines of the blood-testis barrier, which is generally impermeable to peptides, leads us to speculate that tGHRH serves a paracrine or autocrine role in testicular physiology. PMID- 2226321 TI - Expression of gonadotropin-releasing hormone and prothymosin-alpha messenger ribonucleic acid in the ovary. AB - GnRH exerts paradoxical effects on ovarian cells through specific receptors. Based on observed direct effects of GnRH and its antagonists on ovarian functions, the presence of endogenous ovarian GnRH-like peptide(s) has been postulated. In an attempt to detect the ovarian expression of GnRH or related genes at the RNA level, we used the reverse transcription-polymerase chain reaction (RT-PCR) to amplify GnRH mRNA levels. Total RNA from rat ovaries was converted to first strand cDNA using reverse transcriptase and amplified in PCR using a pair of primers complementary to the rat GnRH cDNA. The DNA products obtained were subcloned into plasmid vectors, and their sequences were determined. The most prominent PCR product of 462 basepairs (bp) was unexpectedly identified as a fragment of prothymosin-alpha cDNA previously found in the spleen. This cDNA was obtained because of an identical 10 bp match with the 3' end of one of the GnRH primers. Northern blot analyses using the cloned prothymosin-alpha cDNA as probe revealed the presence of mRNA for this factor in ovary, thymus, testis, placenta, and hypothalamus. RT-PCR amplification of hypothalamus and granulosa cell messages indicated the presence of a 244-bp product with a sequence identical to that of GnRH. To further confirm the presence of GnRH messages in the ovary, a second set of GnRH primers was used. PCR amplification of cDNA from hypothalamus, granulosa cells, and whole ovary yielded a 241-bp product identical to the authentic GnRH sequence based on analysis on both strands. In contrast, no PCR product was evident after amplification of thyroid cDNA. Our data demonstrated the expression of mRNA for GnRH and prothymosin-alpha in the ovary. Although the exact ovarian role of the immune hormone awaits further study, the detection of GnRH transcript in the ovary suggests potential intragonadal roles of this decapeptide. PMID- 2226322 TI - The production of transforming growth factor-beta in the porcine ovary and its secretion in vitro. AB - Porcine granulosa cells isolated from small (1-3 mm in diameter) follicles proliferate rapidly in culture in response to 10% fetal bovine serum (FBS) and epidermal growth factor (EGF) (10 ng/ml). Transforming growth factor-beta (TGF beta) inhibits FBS/EGF-stimulated proliferation in a dose-dependent manner. We have used this proliferation inhibitory property of TGF beta to assay qualitatively, the presence of this growth factor in conditioned medium from cultured follicle cells as well as in partially purified preparations from porcine ovarian compartments. In addition, the concentration of TGF beta in the theca cell conditioned medium was quantitatively estimated by generating a TGF beta-dose-response curve (inhibition of FBS/EGF-stimulated proliferation of granulosa cells in monolayer culture) using authentic human TGF beta-1. Ovarian thecal cells isolated from small and large size follicles in the pig ovary secrete TGF beta-like activity in vitro. Medium conditioned by thecal cells in primary monolayer culture contains a latent form of TGF beta which can be activated by heat or acid treatment. In contrast, and unlike rat granulosa cells, porcine granulosa cells in primary monolayer culture do not secrete detectable levels of TGF beta-like activity in the medium. Incubation of heat-activated thecal cell conditioned medium with a TGF beta-neutralizing antibody (which recognizes TGF beta-1 and 2) but not nonimmune serum attenuated the TGF beta-like activity in thecal cell conditioned medium suggesting that this activity is due to authentic TGF beta. Since many cell types secrete latent TGF beta in the medium when cultured in vitro, we next investigated whether thecal cell secretion of latent TGF beta was a function of cell culture or whether the ovarian thecal compartment actually contained detectable levels of TGF beta-like activity. To this end, we used an acid-ethanol extraction procedure to isolate thecal proteins from fresh-frozen tissue. The acid-ethanol extracted protein fraction was mixed with trace amounts of 125I-TGF beta for detection and chromatographed on Bio-Gel P-60 column under acidic conditions. Elution of TGF beta bioactivity from the Bio Gel P-60 column as measured by inhibition of granulosa cell proliferation correlated with the elution of radioiodinated authentic TGF beta. Preincubation of TGF beta-like activity-containing fractions with TGF beta-neutralizing antibody attenuated the proliferation-inhibitory activity in these fractions. TGF beta activity was also observed in fractions extracted from porcine corpora lutea.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2226323 TI - Endogenous opioid peptides mediate the interleukin-1-induced inhibition of the release of luteinizing hormone (LH)-releasing hormone and LH. AB - We have reported recently that central administration of both the alpha- and beta subtypes of the cytokine interleukin-1 (IL-1) inhibited the estrogen-progesterone induced LH surge in ovariectomized (ovx) rats. This inhibition was probably due to a central effect, since IL-1 alpha and IL-1 beta also suppressed the in vitro LHRH output from the hypothalami of steroid-primed ovx rats. Whether IL-1 inhibits LHRH release by a direct action or via some other neuronal system is not known. Since IL-1 reportedly stimulates the release of POMC peptides, which are known to be inhibitory to the LHRH-LH axis, we have tested the hypothesis that the inhibitory influence of IL-1 may be mediated via activation of hypothalamic opioid peptides. Ovx rats, preimplanted with cannulae in the third ventricle of the brain, were injected with 30 micrograms estradiol benzoate, followed by 2 mg progesterone 48 h later. Three hours after P injection, IL-1 alpha, IL-1 beta, or saline (SAL) was injected intracerebroventricularly (30 ng/3 microliters) at 1300 h, followed immediately by iv infusion of SAL or the opiate antagonist naloxone hydrochloride (NAL; 2 mg/0.6 ml.h) for 2 h. Plasma LH levels were measured in blood samples withdrawn hourly until 1800 h. Both IL-1 alpha and IL-1 beta blocked the afternoon LH surge. NAL infusion into control SAL-injected rats did not alter the LH surge; however, it reversed the IL-1 alpha- and IL-1 beta induced suppression of the LH surge. To determine whether this reversal of IL-1 suppression of the LH surge was due to NAL action at the hypothalamic level, the preoptic area-medial basal hypothalamus of similarly primed ovx rats was obtained at 1300 h and incubated in vitro in the presence of 10 nM IL-1 alpha or IL-1 beta with or without 100 micrograms/ml NAL. Both subtypes of IL-1 suppressed LHRH output significantly. NAL alone did not affect LHRH release, but it completely reversed the inhibitory effects of the cytokine on LHRH release. These results suggest that IL-1 alpha and IL-1 beta inhibit LHRH-LH release by stimulating the activity of hypothalamic endogenous opioid peptide systems. PMID- 2226324 TI - Influence of the fetus and estrogen on serum concentrations and placental formation of insulin-like growth factor I during baboon pregnancy. AB - In the present study, we used an in vivo approach to determine whether the fetus and estrogen have direct effects on placental production and serum concentrations of insulin-like growth factor I (IGF-I) in baboons. On day 100 of gestation, fetuses were removed and placentas left in situ (fetectomy). On days 100-155 of gestation after fetectomy, baboons received 50 mg androstenedione pellets sc in increasing numbers (1-3 every 10 days, n = 8), were injected sc with estradiol (E2) benzoate (0.50-2.5 mg/day, n = 8), or were not further treated (n = 6). Placentas were obtained on day 160, and cells were dispersed in 0.1% collagenase, isolated on 50% Percoll, then incubated for 24 h at 37 C in medium 199. Mean (+/- SE) peripheral serum E2 (nanograms per ml) in untreated baboons (n = 5) was 1.33 +/- 0.06 on days 101-160. Fetectomy decreased (P less than 0.001) E2 to 0.28 +/- 0.04, and androstenedione and E2 after fetectomy increased serum E2 to 0.75 +/- 0.08 and 2.51 +/- 0.23, respectively. Serum IGF-I (nanograms per ml) determined by RIA was 182 +/- 6 on days 101-160 in controls. Serum IGF-I increased (P less than 0.001) rapidly after fetectomy to 403 +/- 22 on days 101-160 and fell precipitously to 185 +/- 8 after placental delivery. Androstenedione and E2 treatment after fetectomy decreased IGF-I to 291 +/- 16 and 239 +/- 6, respectively, values similar to those before fetectomy. Uterine vein concentrations of IGF-I were similar to those in peripheral maternal serum, and the same relative treatment effects were observed. IGF-I secretion (picograms per ml/24 h) by placental trophoblasts of fetectomized baboons (80.1 +/- 9.8) was 242% greater (P less than 0.001) than controls (23.4 +/- 4.7) and decreased after fetectomy by androstenedione (56.7 +/- 15.1) and E2 (62.3 +/- 12.8). Thus, removal of the fetus decreased serum E2 and markedly elevated placental production and maternal serum levels of IGF-I, and these effects were largely reversed by androstenedione or E2. We suggest that the fetus, via secretion of estrogen precursors, regulates placental IGF-I production and consequently maternal serum concentrations of IGF-I during primate pregnancy. PMID- 2226325 TI - Hypoglycemic potency and metabolic clearance rate of intravenously administered human proinsulin and metabolites. AB - Since circulating proinsulin has been suggested to be important in the pathogenesis of noninsulin-dependent diabetes, and biosynthetic human proinsulin (HPI) may have a therapeutic role in patients with diabetes mellitus, the biological activity of proinsulin metabolites is of potential significance. Moreover, recent studies have suggested that the majority of circulating proinsulin immunoreactivity consists of metabolites. We, therefore, compared the blood glucose-lowering ability and MCR of the two proinsulin metabolites des (31,32)HPI and des-(64,65)HPI with intact HPI in seven anesthetized dogs after an overnight fast. Intravenous bolus injections of 12.5 micrograms HPI/kg BW and equimolar amounts of des-(31,32)HPI and des-(64,65)HPI were given on three separate occasions. In addition to blood glucose, des-(31,33)HPI, des-(64,65)HPI, and HPI were measured using an insulin RIA and peptide-specific standard curves. Kinetic parameters were derived by fitting two exponentials to the respective decay curves. The MCR of HPI (3.3 +/- 0.1 ml/kg.min) was significantly lower (P less than 0.05) than that of des-(64,65)HPI (6.4 +/- 0.6 ml/kg.min), but was not significantly different from that of des-(31,32)HPI (3.8 +/- 0.4 ml/kg.min). The MCR of biosynthetic insulin (17.2 +/- 1.8 ml/kg.min), as measured in three of the dogs, was higher than that of HPI or the two metabolites. The blood glucose lowering ability (defined as nadir glucose/fasting glucose, expressed as a percentage) of des-(64,65)HPI (49.3 +/- 5.0%) was significantly greater (P less than 0.05) than that of intact HPI (87 +/- 2.2%), and the glucose-lowering ability of des-(31,32)HPI (75.2 +/- 3.8%) was intermediate. In conclusion, HPI metabolites are more biologically active than intact HPI. The extent of in vivo conversion of proinsulin to metabolites may enhance the biological activity of proinsulin and, thus, have physiological, pathophysiological, and therapeutic significance. PMID- 2226326 TI - Third-ventricular infusion of neuropeptide Y suppresses luteinizing hormone secretion in ovariectomized rhesus macaques. AB - Neuropeptide Y (NPY) has been shown to modulate gonadotropin secretion in an estrogen-dependent manner in the rat and rabbit, and to act centrally in these species to alter GnRH release. The present study examined the ability of centrally administered NPY to affect LH secretion in the primate. Human NPY (hNPY) was administered into the third cerebroventricle of unanesthetized, freely moving, ovariectomized (OVX), or estradiol (E2)-treated OVX rhesus monkeys. LH was measured in blood samples collected remotely at 10-min intervals throughout the experiments. An extensive range of NPY doses was tested in a preliminary study in which OVX monkeys received a 3-h control infusion of Krebs Ringer phosphate buffer (KRP) followed immediately by a 3-h infusion of hNPY (0.1-50 micrograms/h). Only doses greater than or equal to 5 micrograms/h produced a consistent and marked suppression of LH (5 micrograms/h; 35.1 +/- 7.2% reduction, P less than 0.05, n = 4). A longer duration study was performed to better characterize changes in LH pulse frequency and amplitude produced by hNPY treatment. We administered 5 micrograms/h and 15 micrograms/h to OVX (n = 5) and E2-treated OVX (n = 4) monkeys according to the following protocol: 8 h control KRP/8-h hNPY/6-h recovery KRP. In OVX monkeys, LH was suppressed after 2 to 3 h of peptide infusion (P less than 0.01); LH secretion returned to normal after treatment. Both doses of hNPY suppressed mean LH by approximately 55% (P less than 0.05) and LH pulse frequency by approximately 69% (P less than 0.025). LH pulse amplitude was unaffected. In E2-treated OVX monkeys, neither dose of hNPY affected mean LH or LH pulse amplitude. LH pulse frequency was suppressed by approximately 65% (P less than 0.05) during 15-micrograms/h treatment. Because centrally administered hNPY reduced LH pulse frequency and thereby mean LH levels, our results support a central, neural action of NPY to affect the GnRH/LH secretory system. The ability of estrogen feedback to alter the response to NPY treatment supports a physiological role for NPY in controlling reproduction in the primate. PMID- 2226327 TI - Alterations in phospholipase A2 activity during luteal regression in pseudopregnant and pregnant rats. AB - The activity of phospholipase A2 was measured in microsomes prepared from ovaries of superovulated pseudopregnant rats during spontaneous and prostaglandin F2 alpha-induced regression and during regression in pregnant rats. Microsome samples were incubated at 40 C for 90 min in Tris buffer (pH 8.3) with 1.0 mM CaCl2 added. The substrate, radiolabeled phosphatidylcholine, was incorporated into liposomes. During spontaneous regression, there was a significant 2- to 4 fold increase in phospholipase A2 activity, when compared with levels at mid pseudopregnancy (days 8-9). This elevation was correlated with a significant decrease in plasma progesterone concentration. On day 6 or 7 of pseudopregnancy, treatment of rats with luteolytic doses of prostaglandin F2 alpha also caused a significant increase in phospholipase A2 activity, which remained elevated throughout the 72-h sampling period. In pregnant rats there was a small but significant rise in phospholipase A2 activity after parturition. These results indicate that the activity of phospholipase A2 increases during luteal regression in pregnant and pseudopregnant rats and that it could be involved in the mechanism that causes the loss in progesterone secretion. PMID- 2226328 TI - Differential response of luteinizing hormone receptor and steroidogenic enzyme gene expression to human chorionic gonadotropin stimulation in the neonatal and adult rat testis. AB - To study further the functional differences of the fetal-neonatal and adult growth phases of Leydig cells, neonatal (5-day-old) and adult (60-day-old) male rats were challenged with a 600 IU/kg injection of human CG (hCG). Certain Leydig cell responses were monitored 1, 2, and 3 days after the hCG injection. The down regulation of LH receptors and blockage of the 17-hydroxylase/C17-20 lyase step in adult testis, and the absence of these responses in neonatal testis were confirmed. Novel data were obtained on concomitant responses of LH receptor and steroidogenic enzyme messenger RNAs (mRNAs). The LH receptor mRNA was increased 4 5-fold by 2 days after hCG injection in the neonatal testis (P less than 0.05), but in the adult was decreased during all 3 days by 50% (P less than 0.05). The mRNA level of the cytochrome P450 for cholesterol side chain cleavage responded similarly at both ages, with a 180-260% increase during 2 and 3 days (P less than 0.05-0.01). In contrast, the 17-hydroxylase/17,20-lyase cytochrome P450 mRNAs displayed opposite responses, increasing 4.5-fold in 2 days (P less than 0.01) in the neonates, but decreasing by 80% in 1 day in the adults (P less than 0.01). No response of the aromatase cytochrome P450 mRNA to hCG stimulation was found at either age studied. These results demonstrate that the functional differences of the neonatal and adult Leydig cells to high gonadotropic stimulation occur at the level of expression of specific genes, including those of the LH receptor and the 17-hydroxylase/17,20-lyase cytochrome P450. Although aromatization of testicular androgens has been suggested to mediate the blockade of the 17-hydroxylase/C17-20 lyase step in adult testes, altered steady state levels of aromatase mRNA are not involved in this response. LH receptor mRNA decreases in adult rat testis in response to treatment with high levels of hCG. Thus, this phenomenon of down regulation of membrane receptors includes a decreased LH receptor mRNA as well as cellular internalization of the existing receptors. PMID- 2226330 TI - Parathyroid hormone messenger ribonucleic acid in the rat hypothalamus. AB - Polyadenylated RNA, extracted from rat hypothalami, cross-hybridized with a RNA probe complementary in sequence to rat PTH (rPTH) messenger RNA (mRNA). Amplification of complementary DNA (cDNA) by the polymerase chain reaction also demonstrated the presence of rPTH mRNA in the rat hypothalamus and parathyroid gland. rPTH mRNA was localized by in situ hybridization in the paraventricular and supraoptic nuclei of the rat hypothalamus. These results demonstrate the expression of the PTH gene in the central nervous system of the rat in areas which suggest roles for PTH in neuroendocrine function. PMID- 2226329 TI - Insulin-like growth factor type I increases concentrations of messenger ribonucleic acid encoding cytochrome P450 cholesterol side-chain cleavage enzyme in primary cultures of porcine granulosa cells. AB - Insulin-like growth factor type I (IGF-I) is an important intraovarian peptide that stimulates granulosa cell steroidogenesis during follicular development. The cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) that converts cholesterol to pregnenolone is the rate-limiting step in progesterone biosynthesis. Since treatment of primary cultures of immature porcine granulosa cells with IGF-I will increase progesterone production as well as the synthesis of immunoprecipitable P450scc enzyme, we examined possible molecular mechanisms subserving these inductive effects of IGF-I. To this end, cultures of porcine granulosa cells were maintained in serum-free medium with or without IGF-I under various treatment paradigms. Cellular concentrations of specific P450scc mRNA were measured by Northern blot hybridization using a 32P-labeled 1-kilobase porcine cDNA clone. Northern blot autoradiogram densitometry data were normalized with a constitutively expressed 1.2-kilobase chicken glyceraldehyde-3-phosphate dehydrogenase cDNA clone. Steroidogenesis was monitored by measuring concomitant progesterone accumulation in the culture medium. Treatment with pure recombinant human IGF-I (100 ng/ml) significantly increased P450scc mRNA concentrations after 18 h, and maximal stimulation (10- to 20-fold) occurred by 48 h for both P450scc mRNA and progesterone accumulation. The IGF-I dose-response curve studied at 48 h showed a significant increase in P450scc mRNA levels at a minimal IGF-I concentration of 1 ng/ml (although progesterone production was not increased). Treatment with equimolar concentrations of epidermal growth factor, IGF-I, or insulin significantly increased P450scc mRNA concentrations, whereas fibroblast growth factor did not. To examine possible mechanisms underlying stimulation of P450scc by IGF-I, immature granulosa cells were treated with aminoglutethimide (a P450scc enzyme inhibitor), low density lipoprotein (to increase cholesterol delivery to granulosa cells), or estradiol in the presence or absence of IGF-I. Aminoglutethimide had no effect, alone or with IGF-I, on P450scc mRNA concentrations, but suppressed progesterone production. Low density lipoprotein alone also did not stimulate P450scc mRNA levels and only slightly increased progesterone accumulation, but acted synergistically with IGF-I to augment P450scc mRNA concentrations and progesterone accumulation. Estradiol alone did not stimulate P450scc mRNA concentrations, but did significantly increase progesterone production. Estradiol cotreatment with IGF-I synergistically enhanced progesterone production, but did not alter IGF-I-stimulated P450scc mRNA concentrations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2226331 TI - Gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists do not alter endogenous GnRH secretion in short-term castrated rams. AB - The administration of GnRH agonists and antagonists suppresses pituitary LH secretion. However little is known about their effects on endogenous GnRH secretion. To determine if GnRH analogs act on GnRH secretion through a short or ultrashort loop feedback mechanism, experiments were performed to analyze GnRH secretion in hypophyseal portal blood of conscious short-term castrated rams under both agonist or antagonist treatment. In Study 1, six rams were castrated and surgically prepared for portal blood collection on day -7. Portal and peripheral blood were collected simultaneously every 10 min for 14-15 h on day 0. Five hours after the beginning of the portal blood collection, animals were injected im with 5 mg potent GnRH antagonist (Nal-Glu). In Study 2, six rams were treated daily from day -11 to day 0 with the GnRH agonist D-Trp6 GnRH (0.5 mg im). Castration and surgical preparation for portal blood collection were performed on day -7. On day 0 portal and peripheral blood were collected simultaneously every 10 min for 10-11 h. In both studies, to determine whether an increase in GnRH concentration in hypophyseal portal blood can overcome the inhibitory effect of the GnRH analogs, between 5 and 5.5 h after the injection of the analogs, endogenous GnRH secretion was stimulated by Naloxone administration (3 x 100 mg, iv, at 30-min intervals) followed by a bolus of exogenous GnRH (2 x 10 micrograms, iv at 30-min intervals). In Study 1, Nal-Glu administration led to a rapid cessation of pulsatile LH secretion for the duration of blood collection while GnRH pulse frequency and amplitude were not affected. GnRH and LH pulse frequency before and after Nal-Glu administration were, 6.2 +/- 0.6 vs. 5.7 +/- 0.8 (NS) and 5.3 +/- 0.3 vs. 0.3 +/- 0.2 pulses/6 h (P less than 0.001) respectively. In Study 2, peripheral LH secretion was completely suppressed while GnRH secretion (portal blood) remained pulsatile. GnRH pulses frequency and pulse amplitude were 4.3 +/- 0.3 pulses/6 h and 43.0 +/- 4.7 pg/ml, respectively. In both experiments, neither stimulation of endogenous GnRH secretion by naloxone nor administration of exogenous GnRH allowed reinitiation of LH secretion. However, additional studies in two animals of each treatment group (study-III) showed that this was clearly a dose related effect in antagonist treated but not in agonist-treated animals since higher doses of exogenous GnRH (i.e. 100 micrograms or 1000 micrograms) can increase significantly LH levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2226332 TI - Localization of the vicinal dithiols involved in steroid binding to the rat glucocorticoid receptor. AB - Our previous studies with the thiol-specific reagent methyl methanethiolsulfonate (MMTS) and the vicinal dithiol-specific reagent sodium arsenite have established that 2 spatially close thiols (i.e. vicinal dithiols) are involved in steroid binding to the intact 98 K rat glucocorticoid receptor. These 2 thiols form an intramolecular disulfide after treatment with low concentrations of MMTS. One of these thiols was proposed to by Cys-656. In an effort to identify both thiols, we have examined the effects of MMTS and arsenite on proteolytic fragments of the receptor, which contain progressively fewer cysteines. MMTS and arsenite are now found to cause the same dithiothreitol-reversible inhibition of steroid binding and affinity labeling of both the 42 K chymotrypsin fragment and the 16 K steroid binding core fragment of the receptor as was seen for the intact receptor. Characteristic responses include a bimodal inhibition curve for steroid binding after preincubation with MMTS and an inhibition of binding by very low concentrations of arsenite. Low concentrations of MMTS could block steroid binding by forming a disulfide bond between the receptor and a tightly associated, nonreceptor protein. However, no evidence for such cross-linking was observed when intact 98 K receptors, 42 K chymotrypsin fragments, or 16 K trypsin fragments were treated with various concentrations of MMTS, separated on nonreducing sodium dodecyl sulfate-polyacrylamide gels, and visualized by Western blotting with antiheat shock protein 90 or antireceptor antibodies. One of the antireceptor antibodies (aP1) that had been raised against the rat receptor sequence 440-795 was now found to recognize at least 1 epitope in the 16 K core fragment. We conclude that the vicinal dithiols involved in steroid binding are 2 of the 3 cysteines in the sequence of Thr537-Arg673. PMID- 2226333 TI - Further studies on the involvement of protein kinase C in human sperm flagellar motility. AB - Addition of the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) or the membrane-permeable diacylglycerol analog, 1-oleoyl-2-acetylglycerol to human sperm resulted in increased motility. The biologically inactive 4 alpha-phorbol 12,13 didecanoate had no effect on flagellar motility. Basal motility was markedly reduced in the absence of Ca2+ in the incubation medium, but TPA-induced sperm motility persisted even in the absence of Ca2+. Sperm motility was also enhanced by the Ca2+ ionophore ionomycin in a Ca2(+)-dependent, protein kinase c (PKC)-independent fashion. Although all stimulants examined here reached maximal response at about 15 min of incubation, nevertheless whereas the effect of TPA and 1-oleoyl-2-acetylglycerol declined at 60 min of incubation, that of ionomycin still persisted. Human sperm PKC activity is extremely low and represents only about 20% and 25% of the specific activity recovered from PC-12 and rat pituitary cells, respectively. Immunohistochemical analysis using various type-specific PKC antibodies revealed staining only in the equatorial segment and the principal piece of the tail. Thus, PKC is present in human ejaculated sperm and is involved in flagellar motility. PMID- 2226334 TI - Opposing effects of ethanol on pig ovarian adenylyl cyclase desensitized by human choriogonadotropin or isoproterenol. AB - Pig ovarian follicular membranes contain a gonadotropin-responsive adenylyl cyclase, which becomes partially desensitized (approximately 40%) upon a 40-min incubation with a saturating concentration of human (h) CG. This in vitro desensitization is time and hormone dependent and also requires the presence of micromolar concentrations of GTP. In this report we show that 10% ethanol present during the desensitization phase of the incubation increases the extent of hCG induced desensitization of adenylyl cyclase by 2-fold. Ethanol shortened the time necessary to reach maximal hCG-induced desensitization from 20 to 10 min, but had no effect on the dose dependency for GTP. In addition, ethanol had no effect on the affinity of the LH/hCG receptor for 125I-hCG but did cause an increase in the ED50 of hCG for inducing desensitization from 0.25 to 0.75 nM. Interestingly, ethanol decreased the apparent number of LH/hCG-receptor sites by 55%, yet the control hCG-sensitive adenylyl cyclase activity was not reduced. The "hyperdesensitized" state achieved in the presence of ethanol could not be reversed by washing the membranes and incubating them in ethanol-free medium. NaF sensitive adenylyl cyclase was also not impaired in hCG-desensitized membranes from control or ethanol-treated samples. Thus, hCG-induced desensitization was not due to a defect in the functioning of the stimulatory guanine nucleotide binding regulatory protein (G8) or catalytic subunits, but rather was caused by an impairment of the coupling of the lutropin (LH)/hCG receptor with G8, which was exacerbated further by ethanol. In spite of the effect of ethanol on hCG induced desensitization, this agent had an inhibitory effect on isoproterenol induced desensitization of isoproterenol-responsive luteal adenylyl cyclase. These results indicate that membrane fluidity is important in modulating the structure and functional interaction of the LH/hCG receptor with G8 because ethanol is a well known lipid-fluidizing agent. The resistance to ethanol potentiation of desensitization of the isoproterenol-sensitive adenylyl cyclase suggests that there are differences between the LH/hCG- and beta-adrenergic receptors in factors controlling their structures and or interactions with G proteins, and that there is a fundamental difference in their mechanisms of desensitization. PMID- 2226335 TI - Identification of prolactin-like proteins synthesized by normal murine lymphocytes. AB - Cultured murine lymphoid cells release a PRL-like immunoreactive (IR) protein which may be important in immunity, as anti-PRL antisera inhibit lymphocyte proliferation in vitro. We examined culture supernatants (SNs) and cell lysates from concanavalin A (Con A) activated murine thymocytes to identify these proteins. Western blot analysis of cell lysates revealed three specifically stained PRL-IRs. A doublet of bands at 35.6 and 33.6 kDa was associated with the particulate fraction of the cell. These PRL-IRs were present in lymphocytes independently of mitogen stimulation. In contrast, a 22 kDa PRL-IR was only produced in mitogen stimulated cells, and was specifically immunoprecipitated with anti-PRL antiserum. In addition, all three PRL-like IRs incorporated 35S methionine in vitro, indicating that they are synthesized by these cells. Only the 22 kDa PRL-like protein was present in culture medium from stimulated cells, suggesting that this may be the PRL bioactivity previously demonstrated in SNs from murine lymphocytes. PMID- 2226336 TI - Triphasic AVP secretion in encephalopathy. AB - A patient with encephalopathy developed triphasic changes in the clinical course, starting with diabetes insipidus (DI), then the syndrome of inappropriate ADH secretion (SIADH), and followed by the final phase of DI. The clinical course of encephalopathy was very rapid. The patient lost consciousness completely within only one day after the onset. During the early phase, he lapsed into a condition of "brain death". We could not identify the etiology of the encephalopathy. The triphasic change referred to above is similar to previous reports of cats model after stereotactic destruction of the supraopticohypophyseal tract. We speculate that our case may have been associated with neurohypophyseal dysfunction caused by supraopticohypophyseal tract damage. PMID- 2226337 TI - Epidermal growth factor stimulate cell proliferation and inhibits prolactin secretion of the human decidual cells in culture. AB - Epidermal growth factor (EGF) has been found to be mitogenic in a variety of tissues. We investigated the biological effect of EGF on early pregnant human decidua and the non-pregnant decidualized human endometrium in the primary cell culture. EGF had a stimulatory action on cell proliferation in the early pregnant decidual cells and an inhibitory effect on prolactin (PRL) secretion from the decidual cells. The addition of progesterone into culture medium suppressed cell proliferation of decidual cells, whereas it enhanced PRL secretion from decidua. The analysis of the specific receptor for EGF in the early pregnant decidua and non-pregnant decidualized endometrium revealed that both tissues had a single component EGF receptor with a dissociation constant of nM order. These results suggest that EGF may play a role in the growth and function of endometrial stromal cells. PMID- 2226338 TI - DNA replication in uterine cells of adult and prepubertal mice under normal and hormonally stimulated conditions detected by bromodeoxyuridine labeling method. AB - To confirm the utility of the bromodeoxyuridine (BrdU) labeling method in the study of cell proliferation in mouse uterine tissues, changes in the labeling index in the luminal and glandular epithelia, the periluminal, periglandular and deep stromal regions and the myometrium were surveyed in normal adult mice during the estrous cycle and early pregnancy, in prepubertal mice and in ovariectomized adult and young animals treated with estrogen and/or progesterone. All results obtained were consistent with those obtained in previous histometric and autoradiographic studies and proved the effectiveness of the BrdU labeling method in the study of the uterus as well as many other organs. A marked rise in the labeling index was found in the luminal epithelium at metestrus, as well as on the proestrous morning, indicating the occurrence of extensive cell proliferation in the absence of estrogen stimulation. The change in the labeling index in adult mice was much more evident in the luminal epithelium than in the glandular epithelium in all conditions examined. On the other hand, the change in the stroma was more eminent in the periglandular region than in the periluminal and deep regions in most conditions. In immature mice, a great increase in labeling incidence occurred not only in luminal epithelium but also in muscle layers along with the process of puberty and at the time of estrogen stimulation. A moderate increase in the incidence also occurred in all other areas of the uterus including the perimetrium. Again, the increase was more prominent in the periglandular area than in other stromal regions. PMID- 2226340 TI - Hypothalamic luteinizing hormone-releasing hormone (LHRH) and LH secretion in aging female rats. AB - Age-related changes in hypothalamic luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH) secretion were studied in young (6 months), middle aged (12 months) and old (18 months) female rats. The LHRH levels in the mid hypothalamic area were higher in intact middle-aged and old females than in young ones. Additionally, there was no age difference in the hypothalamic LHRH levels in male rats. In order to clarify the significance of this age-related increase in female rats, we examined the effects of progesterone treatment in estrogen primed ovariectomized young and old rats on the LHRH levels in the median eminence (ME) and on plasma LH levels. We found phasic changes in ME-LHRH and plasma LH levels in estrogen-primed rats following progesterone treatment in rats of both ages, but the progesterone-induced change in ME-LHRH levels tended to be delayed in old rats compared with young females. This delay may correspond to the delayed onset, slow and low magnitude of plasma LH increase in old females. The ME-LHRH levels were generally higher in old rats than in young rats. Nevertheless, we found that the increase in plasma LH in response to progesterone treatment in estrogen-primed ovariectomized females was smaller in old rats than young rats. These results suggest that the LHRH secretory mechanism changes with age in female rats. Such alterations may result in the accumulation of LHRH in the mid-hypothalamic area and an increase in ME-LHRH. PMID- 2226339 TI - In vivo regulation of hepatic insulin-like growth factor-1 messenger ribonucleic acids with thyroid hormone. AB - Insulin-like growth factor-1 (IGF-1) is synthesized primarily by the liver in response to growth hormone (GH). Thyroid hormone plays a major role in mediating pituitary GH secretion. In order to clarify the effect of thyroid hormone on IGF 1 gene expression, we measured hepatic IGF-1 mRNA levels in rats with thyroid dysfunction. Female Wistar rats were rendered hypothyroid by surgical thyroidectomy or hyperthyroid by daily injections of thyroxine (12 micrograms/day) for 2 weeks. Northern gel analysis of hepatic poly (A) RNA revealed the multiple sizes of the RNA transcripts ranging from 1.6 to 9.0 kb. After 4 weeks, hepatic IGF-1 mRNA levels were suppressed in hypothyroid rats, to less than 20% of control euthyroid animals. These suppressed mRNA levels were restored to euthyroid levels by thyroid hormone replacement for 2 weeks. Hyperthyroid rats, however, did not contain altered levels of hepatic IGF-1 mRNA as compared to euthyroid rats. The gamma-actin mRNA hybridization signal was not altered in hypothyroid or hyperthyroid rats. These results suggest that thyroid hormone regulates the in vivo expression of hepatic IGF-1 mRNA, probably through the mechanism of GH regulation. PMID- 2226341 TI - cDNA cloning of androgen-stimulated mRNAs in rat seminal vesicles: partial characterization of newly isolated cDNA clones, pSv-1 and pSv-2. AB - As the first step in surveying the molecular mechanism of androgen-responsive gene expression in rat seminal vesicles, the effect of androgen on the mRNAs was examined by in vitro translation assay. When the in vitro translation products of mRNAs from castrated animals (48 h) were compared with those from castrated and testosterone-treated animals (48 h) by SDS-PAGE, several discrete bands which were stimulated or repressed in response to androgen were observed in addition to major peptide bands of SVS IV and SVS V. From these findings, we constructed a partial cDNA library from the seminal vesicle poly(A +)RNAs of androgen-treated rats and screened by differential colony hybridization. Two distinct cDNA clones, pSv-1 and pSv-2, whose mRNAs were differentially stimulated in response to androgen and seemed to be expressed specifically in the seminal vesicles, were isolated. pSv-1 and pSv-2 hybridized to mRNAs of 1,600 and 3,500 nucleotides in length, respectively. These cDNA sequences, newly isolated in the present study, may provide useful probes for the study of molecular mechanism of androgen responsive gene expression. PMID- 2226342 TI - cDNA cloning of androgen-repressed mRNA in rat seminal vesicles: partial characterization of a cDNA clone, pSvr-1. AB - When the in vitro translation products of mRNAs from castrated animals (48 h) were compared with those from androgen-treated animals (48 h) to survey the molecular mechanism of androgen-responsive gene expressions in the rat seminal vesicles, some peptide bands which were repressed in response to androgen were observed. From these findings, we constructed a partial cDNA library of poly(A+)RNAs which had been isolated from the seminal vesicles of castrated rats (48 h) and modestly enriched with respect to the concentration of androgen repressed mRNAs by sucrose density gradient centrifugation, and screened by differential colony hybridization. One cDNA clone, pSvr-1, whose mRNA is markedly induced within 24 h after castration of the animal in the seminal vesicles as well as in the ventral prostate, was isolated. pSvr-1 hybridized to a mRNA of 1,700 nucleotides in length. Partial sequence analysis showed that this clone had highly homologous but not identical sequences to those reported for rat sulfated glycoprotein-2. This cDNA clone may provide a useful probe for the study of the negative regulation mechanism of gene expression by androgens. PMID- 2226343 TI - Change in the growth hormone (GH) response to GH-releasing factor (GRF) caused by exogenous GH in short children. AB - To determine whether exogenous GH induces feedback of GH release in children, growth hormone-releasing factor (GRP) tests were performed before and after 10 day GH administration. Sixteen non-obese short boys, aged 5-14 yr, with normal GH response to pharmacological tests were studied. Mean basal and peak serum GH levels in GRF tests before and after exogenous GH were not significantly different. The subjects were divided into two groups, A and B, according to the percent change in integrated areas under the GH curves in GRF tests (GH AUC) before and after 10-day GH administration. Group A consisted of 6 boys with decreased GH AUC and group B consisted of 10 boys with increased GH AUC. Mean peak GH in GRF tests and mean GH AUC were significantly higher before exogenous GH in group A than in group B. The boys in group A were all prepubertal, while 4 boys in group B had begun their early pubertal change. The mean age in group A (7.8 +/- 1.8 yr) was significantly lower than that of group B (11.9 +/- 2.4 yr). GH AUC before exogenous GH showed a significant correlation with the percent change in AUC (= -0.742, p less than 0.01). These data demonstrated that the exogenous GH suppressed the GH response to GRF in prepubertal children with good response to GRF before exogenous GH, while it exaggerated the GH response to GRF in older children with relatively poor response before GH. PMID- 2226344 TI - Hyperparathyroidism associated with Cushing's syndrome due to an adrenal cortical adenoma. AB - Two patients with the rare association of Cushing's syndrome and primary hyperparathyroidism are reported. Initially, both patients suffered from Cushing's syndrome due to adrenal cortical adenomas with typical features and laboratory findings. Five years after treatment of the Cushing's syndrome by removal of the tumor, asymptomatic mild hypercalcemia was incidentally noticed in both patients, which suggested the occurrence of primary hyperparathyroidism. An enlarged parathyroid gland was removed surgically in both cases and was histologically shown to be a parathyroid adenoma. The levels of serum calcium returned to normal after parathyroidectomy. Papillary adenocarcinoma of the thyroid in one patient and adenomatous goiter in the other were also incidentally detected at operation. These findings suggest that Cushing's syndrome resulting from an adrenal cortical adenoma may be another presentation of multiple endocrine neoplasia type I. PMID- 2226345 TI - Plasma growth hormone, insulin-like growth factor-I, and milk production responses to exogenous human growth hormone-releasing factor analogs in dairy cows. AB - Responses of plasma growth hormone (GH) and insulin-like growth factor-I (IGF-I), and milk production to subcutaneous (sc) injection(s) of two synthetic human growth hormone-releasing factor (hGRF) analogs were studied in dairy cows. Two mg of each hGRF analog dissolved in 5 ml saline per cow were injected into the shoulder area of each experimental animal, and jugular venous blood samples were collected via an indwelling catheter or by venipuncture. Plasma GH and IGF-I concentrations were measured by radioimmunoassay methods. In dry cows, the mean concentration of plasma GH after a single sc injection of hGRF analogs rose to 22.0-28.3 ng/ml at about 5 h from 1.4-1.7 ng/ml at 0 h (just before injection), and returned to the level before injection after 10-12 h. On the other hand, the plasma IGF-I began to increase after a lag of 4-6 h following a single injection of hGRF analogs, and reached maximum values of 71.1-89.4 ng/ml at 20 h from 43.7 46.4 ng/ml at 0 h. The IGF-I concentration at 24 h after a single injection of hGRF analogs was still higher than the value for the dry cows given saline. In lactating cows, the plasma concentration of GH at 2 h after daily sc injections of hGRF analogs during 14 consecutive days (an injection period) was higher than those for the lactating cows which received saline. Also, during the injection period, the concentration of IGF-I was higher in the lactating cows which received hGRF analog injections than in the cows which received saline injections. During the last 7 days of the injection period, the administration of hGRF analogs increased the mean milk yield by 11-19% in comparison with those for the saline injected cows. A positive correlation was observed between the mean plasma IGF-I concentration and the mean milk yield in the lactating cows treated with hGRF analogs throughout the injection and a postinjection (11 consecutive days after cessation of hGRF analog injection) periods. The results demonstrate that a single sc injection of hGRF analogs stimulates both GH release and the circulating level of IGF-I in dry cows, and that daily sc injections of hGRF analogs over 14 days enhance milk production, and plasma GH and IGF-I levels in lactating cows. PMID- 2226346 TI - The participation of sterol carrier protein2 in cholesterol esterification in rat adrenal microsomes. AB - The effect of sterol carrier protein2 (SCP2) purified from rat liver on the formation of cholesterol esters by acyl-CoA: cholesterol acyl-transferase (ACAT: EC 2.3.1.26) in rat adrenal microsomes was studied. The rate of incorporation of [1-14C]oleoyl-CoA into cholesteryl oleate was determined in the presence or absence of exogenously added cholesterol or SCP2, or both. The addition of SCP2 had no effect on the formation of cholesterol esters from endogenous cholesterol by ACAT in rat adrenal microsomes. In contrast, the formation of cholesterol esters from exogenous cholesterol by ACAT was dose-dependently increased by the addition of SCP2. These experiments showed that SCP2 had an enhancing effect on cholesterol esterification by ACAT in rat adrenal microsomes most likely by modulating the availability of exogenous cholesterol and that SCP2 may participate in the formation of cholesterol esters in the rat adrenal gland. PMID- 2226347 TI - Effects of sc administration of recombinant human insulin-like growth factor I (IGF-I) on normal human subjects. AB - Recombinant human insulin-like growth factor I (IGF-I) was administered subcutaneously to each of 5 normal human subjects at doses of 0 mg/kg (control), 0.06 mg/kg, or 0.12 mg/kg successively at one week intervals. After 0.06 mg/kg or 0.12 mg/kg IGF-I injections, plasma IGF-I levels increased from 185 +/- 17 ng/ml (mean +/- SEM) to maximal levels of 396 +/- 21 ng/ml at 3 hours and from 169 +/- 14 ng/ml to 480 +/- 27 ng/ml at 4 hours, respectively. These two peak values were statistically different (p less than 0.05). After 0.06 mg/kg and 0.12 mg/kg IGF-I administration, blood glucose levels decreased from 85 +/- 2 mg/dl to minimal levels of 73 +/- 3 mg/dl at 3 hours and from 83 +/- 1 mg/dl to 50 +/- 4 mg/dl at 2 hours, respectively. These two minimal values were statistically different (p less than 0.001). Serum insulin and C-peptide levels were decreased in a dose dependent manner after IGF-I administration. There were no changes between blood urea nitrogen levels before and 4 hours after IGF-I administration. The urinary GH concentration decreased after 0.06 mg/kg IGF-I administration, but increased and maintained normal values after 0.12 mg/kg IGF-I administration. PMID- 2226348 TI - The tissue matrix: cell dynamics and hormone action. PMID- 2226349 TI - Metabolism and effects of epidermal growth factor and related growth factors in mammals. AB - The initial observations of Stanley Cohen in the 1960s established that EGF induced in vivo effects such as precocious eyelid opening and tooth eruption. Subsequently the actions of EGF have been extensively explored in cell culture systems. The receptor for EGF was characterized as a prototype model for other growth factors and the now extensive in vitro data indicate multiple functions for EGF. Moreover, EGF and EGF receptors have been characterized in many tissues, and EGF has been identified in most body fluids of several mammalian species. Interestingly, neither EGF antibody administration to newborn animals nor passive immunization of pregnant rodents against EGF has caused major deleterious effects (except the delay in epidermal maturation events), as might be expected from the in vitro studies. This is in contrast to the effects of nerve growth factor antiserum in developing rodents. Also, to date, no pathological EGF deficiency disorder has been characterized. However, the EGF family of growth factors appears to be important in mammalian development and function, although the precise roles and significance are not yet clear. Members of the family may have a role in embryogenesis and fetal growth since receptors have been identified in fetal tissues. Available evidence suggests that TGF alpha subserves the growth factor family roles in fetal development. In the developing postnatal animal pro EGF mRNA, immunoreactive EGF, immunoreactive TGF alpha, and EGF receptors are present in many tissues. EGF also is produced and secreted by the maternal mammary gland, and mammary derived EGF appears to be important in gut development in the neonatal rodent. There is now extensive data to indicate important hormone EGF interactions. In the postnatal period, thyroid and steroid hormones including retinoic acid have been shown to modulate EGF and/or EGF receptors in several tissues. GH increases EGF binding in liver and increases urine EGF concentrations. Moreover, EGF stimulates secretion of several hypothalamic and pituitary hormones, increases placental production of hCG and human chorionic somatomammotropin, increases adrenal cortisol production, and inhibits testicular, ovarian, and thyroid hormone secretions. As summarized in this review EGF has been implicated in a number of developmental events including palate and skin differentiation, growth of hair follicles, eye opening and tooth eruption, lung maturation, gut and liver growth, and differentiation of neurons. These EGF actions probably are mediated via autocrine, paracrine, and endocrine routes. A role for salivary and urine EGF in the maintenance of adult stomal, gut, and urinary epithelial surface integrity seems likely, although not yet proven.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2226350 TI - Uterine insulin-like growth factor-1: regulation of expression and its role in estrogen-induced uterine proliferation. PMID- 2226351 TI - The potential relevance of cytokines to ovarian physiology: the emerging role of resident ovarian cells of the white blood cell series. PMID- 2226352 TI - Effect of transforming growth factor beta on synthesis of glycosaminoglycans by human lung fibroblasts. AB - The processes of lung growth, injury, and repair are characterized by alterations in fibroblast synthesis and interstitial distribution of extracellular matrix components. Transforming growth factor beta (TGF-beta), which is postulated to play a role in modulating lung repair, alters the distribution of several matrix components such as collagen and fibronectin. We studied the effect of TGF-beta on the synthesis and distribution of the various glycosaminoglycans (GAGs) and whether these effects may explain its role in lung repair. Human diploid lung fibroblasts (IMR-90) were exposed to various concentrations of TGF-beta (0-5 nM) for variable periods of time (0-18 h). Newly synthesized GAGs were labeled with either [3H]glucosamine or [35S]sulfate. Individual GAGs were separated by size exclusion chromatography after serial enzymatic and chemical digestions and quantitated using scintillation counting. There was a dose-dependent increase in total GAG synthesis with maximal levels detected after 6 h of exposure. This increase was noted in all individual GAG types measured and was observed in both the cell associated GAGs (cell-matrix fraction) as well as the GAGs released into the medium (medium fraction). In the cell-matrix fraction, TGF-beta increased the proportion of heparan sulfate that was membrane bound as well as the proportion of dermatan sulfate in the intracellular compartment. In the medium fraction, TGF beta increased the proportion of hyaluronic acid, chondroitin sulfate and dermatan sulfate released. We conclude that the role of TGF-beta in lung growth and repair may be related to increased synthesis of GAGs by human lung fibroblasts as well as alterations in the distribution of individual GAGs. PMID- 2226353 TI - Conditioned medium from irradiated bovine pulmonary artery endothelial cells stimulates increased protein synthesis by irradiated bovine lung fibroblasts in vitro. AB - Pulmonary fibrosis, a potentially fatal consequence of radiation exposure, occurs by unknown mechanisms. The hypothesis that endothelial cells, injured by radiation, could alter the biochemical function of lung fibroblasts, was tested by exposing cultures of bovine pulmonary artery endothelial cells to 0 or 5 Gy radiation and then incubating them in fresh medium for 48 h. This endothelial cell conditioned medium (ECCM) was then applied to irradiated or nonirradiated cultures of bovine lung fibroblasts. Forty-eight hours later the fibroblasts were analyzed for their ability to synthesize DNA and protein. The ECCM from injured cells stimulated fibroblast protein synthesis twofold to threefold in irradiated fibroblasts without increasing DNA synthesis. It also stimulated a significant but less marked increase in protein synthesis in nonirradiated fibroblasts. Two dimensional gel electrophoresis revealed this increased synthesis to be expressed in less than 10% of the 1100 separable fibroblast proteins. This study shows that endothelial cells injured by radiation produce factors that stimulate injured fibroblasts to markedly increase their synthesis of certain intracellular proteins, while not stimulating fibroblast replication. PMID- 2226354 TI - Body temperature alters the lipid composition of pulmonary surfactant in the lizard Ctenophorus nuchalis. AB - In any 24-h period the body temperature (Tb) of the central Australian agamid lizard, Ctenophorus nuchalis, may vary from 13 to 45 degrees C; the mean preferred Tb is 37 degrees C. We have analyzed surfactant-type lipids in lizards that underwent rapid changes in Tb from 37 degrees C to 14, 19, 27, or 44 degrees C. Lipids were extracted from lung lavage and lamellar body fractions, and phospholipids and cholesterol components were measured. There was no change in either the total amount or relative proportions of the different classes of phospholipids, but cooling increased the cholesterol content of lavage. An increase in the cholesterol: phospholipid ratio was evident within 2 h of cooling to 19 degrees C and was maintained for at least 48 h. The ratio increased from 8% at 37 degrees C, to 15% after 4 h at 19 degrees C, and 18% after 4 h at 14 degrees C. Possibly the increase in cholesterol promotes fluidity and absorption of surfactant within the alveoli of lizards with low Tb. Cold lizards collapse their lungs during prolonged periods of apnea and the surfactant may prevent the epithelial walls from adhering. PMID- 2226356 TI - Gestational variation of glycerophosphate acyltransferase activity in maternal guinea pig lung and possible role of thyroid hormone in its de novo synthesis. AB - We have observed earlier that the pattern of gestational variation of microsomal glycerophosphate acyltransferase (GAT) activity is similar in maternal and fetal guinea pig lung. Furthermore, there is a close resemblance between these patterns and that of the gestational variation of fetal plasma thyroid hormone. It is known that triiodothyronine (T3) injected to pregnant rats can cross the placenta to some extent and cause an increase in phosphatidylcholine synthesis in fetal lung. It is possible, therefore, that the gestational increase of GAT activity in maternal and fetal lung is associated with an increase in maternal plasma thyroid hormone. The objective of this study was to investigate whether intramuscular injection of T3 to adult guinea pig causes any change in the activity of GAT in lung and, if so, to determine the mechanistic basis. The results indicated that T3 significantly increased the GAT activity in the microsomes but not in the mitochondria. Actinomycin D or cycloheximide abolished the hormone-mediated stimulation of the enzyme in the microsomes, suggesting that T3 is involved in both transcriptional and translational pathways of GAT synthesis. We also confirmed our previous preliminary finding that there is a gestational variation of GAT activity in maternal guinea pig lung and furthermore the increase in GAT activity during pregnancy is predominantly in the microsomes. PMID- 2226355 TI - Migratory behaviors of alveolar macrophages during the alveolar clearance of light to heavy burdens of particles. AB - We investigated the unstimulated and stimulated migratory activities of lavaged alveolar macrophages (AMs) in vitro over the course of alveolar clearance of three different mass lung burdens of microspheres. Our intent was to uncover potentially important relationships between the migratory behaviors of the AM and the retention kinetics of particles. Groups of adult, male Fischer-344 rats were intratracheally instilled with approximately 86 micrograms (low burden, LB), approximately 1 mg (medium burden, MB), or approximately 3.7 mg (high burden, HB) of polystyrene microspheres (2.13 microns diameter), or with carrier vehicle (phosphate buffered saline, PBS) alone. The lung retention kinetics of the particles were determined over an approximately 170 day period. On days 14, approximately 57, and approximately 85, lavaged AMs were assessed for their abilities to migrate through 5-microns pore membranes in response to inactivated rat serum (unstimulated condition) and yeast-activated rat serum (stimulated condition). The retention characteristics of the three burdens could be satisfactorily described by two-component, negative exponential equations. The kinetics of retention of the LB and MB were similar, although some evidence indicated the MB slightly retarded the lung clearance process. Deposition of the HB resulted in more marked prolongations of both the early, more rapid, and the slower, longer term components of alveolar clearance. The unstimulated migration indices of AMs from the particle-instilled lungs were generally not significantly different from those of AMs from PBS-instilled lungs except for a significant increase in the migration indices of LB AMs at the last assay time. The stimulated migration indices of MB and HB AMs were significantly decreased on assay days 14 and approximately 57. On day approximately 85, however, the migration indices of LB, MB, and HB AMs were all increased above the PBS AMs. Comparisons of the frequency distributions of particles in the unstimulated and stimulated AM that migrated to those in corresponding parent AM populations consistently indicated a preferential migration of particle-free AMs and of AMs with lesser loads of microspheres. The overall results of this study suggest that the unstimulated and stimulated migratory activities of particle-laden AMs are depressed in vitro. Our results also suggest that the migratory activities of generally particle-free AMs may be enhanced over a prolonged period of time following the deposition of particles in the lung. PMID- 2226357 TI - Fluorescence polarization changes with gestational age in amniotic fluid of rabbit and guinea pig. AB - The variation of amniotic fluid microviscosity with gestational age was measured in rat, rabbit, and guinea pig. In rat, the changes followed the same pattern as known for women, microviscosity being high during early and mid-gestation and markedly lowering 12 h before delivery. Surprisingly, an opposite trend was observed in rabbit and guinea pig amniotic fluid. Moreover, the lecithin to sphingomyelin ratio markedly rose in late gestation in all species considered. Qualitative and quantitative analysis of lipids and phospholipids were performed in woman and rabbit amniotic fluids at early and late gestational ages. Among all the parameters measured, the most important differences that can influence the amniotic fluid microviscosity are the presence of very high levels of lysophosphatidylcholine both in early and late gestation in rabbit (much higher than in woman) and the cholesterol to total phospholipid ratio which decreased with gestational age in woman but remained stable in rabbit. The Arrhenius plot of the logarithm of microviscosity against the reciprocal of absolute temperature of mature and immature amniotic fluids from woman and rabbit was also determined. The temperature profiles confirmed the differences in lipid profile between woman and rabbit in early and late gestation which could be quantified on a physicochemical basis by determining the activation energy (delta E) at 25 degrees and 37 degrees C for each curve. This confirmed the opposite patterns in woman and rabbit and showed that amniotic fluid from the immature rabbit was the most fluid. PMID- 2226358 TI - Uptake and metabolism of endothelin in the isolated perfused rat lung. AB - The uptake and metabolism of endothelin was studied in the isolated perfused rat lung. 125I-Labeled endothelin (4 x 10(-12) M) was rapidly removed from the lung perfusate. More than 90% of the label was removed by 5 min, and only 4-5% remained in the perfusate after 30 min. In the presence of 10(-9) or 5 x 10(-9) M unlabeled endothelin added 6 min before 125I-labeled endothelin, the radiolabel was more slowly removed, so that after 30 min 19 or 73% of the label, respectively, remained in the perfusate. Although a high level of unlabeled endothelin in the perfusate reduced the uptake of 125I-labeled endothelin, it did not displace radiolabel previously taken up by the lung. Analysis of radiolabel composition showed that endothelin metabolism was less than 15% in both the lung and the perfusate after 30 min of lung perfusion. Autoradiography of the lung indicated that the radiolabel was located primarily within the alveolar wall. These results suggest that circulating endothelin is readily but finitely taken up in the pulmonary microvasculature where it is avidly bound but slowly metabolized. PMID- 2226359 TI - Inhibition of porcine pancreatic elastase-induced emphysema by eglin-c. AB - Eglin-c, a compound that inhibits rat elastase but has little effect on porcine pancreatic elastase (PPE), was employed to examine the role of endogenous elastase in PPE-induced emphysema. Twenty-four female Long-Evans rats were divided into three groups: control (n = 8), PPE (n = 9), and PPE + eglin-c (n = 7). Eglin-c (9 mg/rat) was intratracheally instilled 3 days after PPE treatment, twice weekly, until 3 days before pulmonary function testing. Function tests and lung fixation for morphometric analysis were carried out 15-34 days after PPE treatment. Intratracheal instillation of PPE (400 IU/kg) produced significant increases in functional residual capacity, dynamic and quasi-static compliances, total lung capacity (TLC), and mean linear intercept (MLI), as well as a significant decrease in carbon monoxide diffusion coefficient. However, no significant alterations in quasi-static compliance, TLC, or MLI were found in animals treated with PPE and eglin-c. Three additional groups were used to examine the effects of intratracheal instillation of saline or eglin-c: control (n = 9), saline (n = 8), and eglin-c (n = 10). No significant change in any respiratory parameter was found in either the saline or the eglin-c group, indicating no detectable alteration in pulmonary function caused by either the intratracheal procedure or eglin-c. These data suggest that endogenous elastase is an important contributing factor in the development of PPE-induced emphysema in the rat. PMID- 2226361 TI - Vagus nerve stimulation for the control of epilepsy. Proceedings of a symposium held in conjunction with the American Epilepsy Society annual meeting. Boston, Massachusetts, December 2, 1989. PMID- 2226360 TI - Anatomical, physiological, and theoretical basis for the antiepileptic effect of vagus nerve stimulation. AB - The vagus is a mixed nerve carrying somatic and visceral afferents and efferents. The majority of vagal nerve fibers are visceral afferents and have a wide distribution throughout the central nervous system (CNS) either monosynaptically or via the nucleus of the solitary tract. Besides activation of well-defined reflexes, vagal stimulation produces evoked potentials recorded from the cerebral cortex, the hippocampus, the thalamus, and the cerebellum. Activation of vagal afferents can depress monosynaptic reflexes, decrease the activity of spinothalamic neurons, and increase pain threshold. Depending on the stimulation parameters, vagal afferent stimulation in experimental animals can produce electroencephalographic (EEG) synchronization or desynchronization and has been shown to affect sleep states. The desychronization of the EEG appears to depend on activation of afferent fibers that have conduction velocities of less than or equal to 15 m/s. Vagal afferent stimulation can also influence the activity of interictal cortical spikes produced by topical strychnine application, and either attenuate or stop seizures produced by pentylenetetrazol, 3-mercaptoproprionic acid, maximal electroshock, and topical alumina gel. The mechanisms for the antiepileptic effects of vagal stimulation are not fully understood but probably relate to effects on the reticular activating system. The vagus provides an easily accessible, peripheral route to modulate CNS function. PMID- 2226362 TI - Feasibility and safety of vagal stimulation in monkey model. AB - The feasibility, safety, and preliminary effects of chronic vagal stimulation were studied in an aluminagel monkey model. Pilot studies to perfect the equipment, determine stimulation thresholds, and insure the comfort and safety of the animals preceded this study. Four monkeys were equipped with an indwelling, 2 electrode cuff (titanium bands spaced 7 mm apart; silicone encased; 1.5 cm total length) in contact around the right vagus nerve; avoidance of the cardiac branch was confirmed by electrocardiograms. After postsurgical recovery, the intact and awake animals received constant-current stimulation (5 mA; 83 Hz, 143 Hz, or 50 250 Hz randomly; 0.5-ms pulse width) at the onset of every spontaneous seizure for the duration of the seizure or every 3 h for 40 s if stimulation had not occurred in the preceding hour. Stimulation periods of 2-6 weeks, with differing levels of stimulation, were preceded and followed by at least a 2-week baseline period of no stimulation. During the stimulation periods, the seizure rate decreased to zero in two monkeys and the interseizure intervals became invariable in the remaining two monkeys. These effects carried over temporarily into the poststimulation baseline periods. Vagal stimulation had no consistent effects on seizure severity or EEG interictal spikes. Histological studies of six vagus nerves were unable to separate electrode cuff damage from any direct effects stimulation may have had on the nerves. Although it appears that chronic vagal stimulation is feasible and that epileptogenic processes are influenced, the safety and efficacy of the procedure are still in question. PMID- 2226363 TI - Considerations for safety with chronically implanted nerve electrodes. AB - Electrical stimulation of cranial and peripheral nerves has been used to ameliorate a variety of neurologic disease states and neural injuries over the past 20 years. In this review, clinical applications and the histopathologic results of chronic implants in animals and humans are discussed, and the results of neural damage models developed at Huntington Medical Research Institutes are summarized. Chronically implanted electrode arrays may produce neural injury by either mechanical factors or by continuous, high-frequency electrical stimulation. The margin of safety to avoid electrically induced injury may be increased by minimizing the frequency or total stimulation time, and by the use of an intermittent duty cycle. The protocols presently being used for the stimulation of the vagus nerve to effect inhibition of seizures appear to have an adequate margin of safety. PMID- 2226364 TI - An implantable neurocybernetic prosthesis system. AB - The neurocybernetic prosthesis (Cyberonics, Inc.) is an implantable, multiprogrammable pulse generator that delivers constant current electrical signals to the vagus nerve for the purpose of reducing the frequency and/or severity of epileptic seizures. The device is implanted in a subcutaneous chest pocket just below the clavicle, similar to cardiac pacemaker placement. The stimulation signal is transmitted from the prosthesis to the vagus nerve through a stimulation lead. The prosthesis can be programmed using any IBM-compatible personal computer with programming software and a programming wand. The electrodes used in the first group of patients were found to break at an unacceptable rate. Design modifications appear to have resolved this problem. PMID- 2226365 TI - Surgical technique for implantation of the neurocybernetic prosthesis. AB - The surgical technique for the implantation of the neurocybernetic prosthesis is described in detail. This procedure is straightforward and is easily carried out by surgeons familiar with carotid surgery. PMID- 2226366 TI - Efficacy and safety of vagus nerve stimulation in patients with complex partial seizures. AB - A clinical trial of chronic intermittent vagal stimulation in five patients suggests that the procedure may be safe and effective as adjunctive treatment of medically intractable seizures of partial onset. Patients tolerated well the implantation of the neurocybernetic prosthesis and the vagal stimulation without serious physiological or lifestyle changes. Stimulation of the vagus nerve either reduced the seizure frequency or decreased the duration or intensity of seizures. Adverse side effects were limited to a tingling sensation in the throat and hoarseness during stimulation. A major complication was mechanical interruption of the wire-electrode circuitry, with consequent cessation of stimulation. The small number of patients and the relatively short follow-up period make this a pilot study, but the results are promising. PMID- 2226367 TI - Vagus nerve stimulation in humans: neurophysiological studies and electrophysiological monitoring. AB - Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters behavioral and electrographic seizure activity. We report on effects of electrical stimulation of the vagus nerve in five patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and it is hoped that analysis of electrophysiological effects of vagal nerve stimulation will help elucidate which brain areas are affected. Stimulation of the left vagus nerve in the neck was accomplished with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus-nerve-evoked potential showed some unusual properties: a scalp negative component occurred with latency of 12 ms, very high amplitude (up to 60 microV), and widespread scalp distribution. Field distribution studies indicate that this potential is generated in the neck, in the region of the stimulating electrodes. Muscle paralysis confirms this observation. Stimulation at various frequencies had no noticeable effect on electroencephalographic (EEG) activity regardless of whether the patient was under general anesthesia, awake, or asleep. PMID- 2226368 TI - Effects of vagal stimulation on experimentally induced seizures in rats. AB - Repetitive stimulation of the vagus nerve inhibits chemically induced seizures in dogs. We report here the results and conclusions from studies designed to answer some of the immediate questions raised by this finding. (1) Maximal stimulation of vagal C fibers at frequencies greater than 4 Hz prevents or reduces chemically and electrically induced seizures in young male rats. (2) Antiepileptic potency is directly related to the fraction of vagal C fibers stimulated. (3) Vagal stimulation shortens but does not shut down a chemical seizure once it has begun. (4) In rats, optimal stimulus frequency is approximately 10-20 Hz; duration of stimulus, 0.5-1 ms; and stimulus strength, 0.2-0.5 mA/mm2 of nerve cross-section. These results, when taken together with similar results obtained from dogs, monkeys, and humans, strongly suggest that periodic stimulation of the vagus nerve using appropriate stimulation parameters is a powerful method for preventing seizures. The data from the literature suggest that the antiepileptic actions of vagal stimulation are largely mediated by widespread release of GABA and glycine in the brainstem and cerebral cortex. The probable pathway is via projections from the nucleus of the solitary tract to the reticular formation and thence by diffuse projections to the cortex and other areas. Intermittent vagal stimulation has the potentiality of reducing the number and/or the intensity of seizures in patients with intractable epilepsy. These results indicate that feasibility studies in humans should be continued and expanded. PMID- 2226369 TI - Epileptic syndromes: genetic, diagnostic, and therapeutic aspects. Ninth annual Merritt-Putnam Symposium. December 7, 1989, Boston, Massachusetts. Proceedings. PMID- 2226370 TI - The epilepsies: clinical implications of the international classification. AB - From the earliest days of neurology, the classification of epileptic seizures into those generalized from the beginning and those with a definable localization in the cortex from the onset has added to knowledge about the function of the nervous system. Further elaboration of the classification of seizures into those localized to the six-layered isocortex and those whose elaboration involves regions of the brain involved with consciousness and memory has provided the basic focus for the burgeoning subspecialty of epilepsy surgery. It is increasingly apparent that the etiology of a seizure disorder is of at least equal or of greater significance than the nature of the seizures it spawns and is the product not only of localization in the nervous system but also of causative factors with implications reaching into areas of genetics, higher cortical function, and intelligence. The prognosis concerning the outcome of the epilepsy under consideration is based on all of these facets. This pathophysiological substratum, of which the seizure is only the presenting symptom, constitutes the epilepsy or epileptic syndrome on which the formulation of a rational treatment plan is based. PMID- 2226371 TI - Experimental models of temporal lobe epilepsy: new insights from the study of kindling and synaptic reorganization. AB - Temporal lobe epilepsy is a common localization-related epileptic syndrome characterized by complex partial seizures, ictal and interictal epileptic discharges arising from limbic structures of the temporal lobe, and association with hippocampal sclerosis. Temporal lobe epilepsy may follow perinatal injury and febrile convulsions, may be progressive, and frequently becomes refractory to standard antiepileptic therapy. The neurobiology that underlies these features of temporal lobe epilepsy is not known. Recent studies in experimental models have provided new insights that may help clarify the relationship of seizures, hippocampal sclerosis, and temporal lobe epilepsy. Observations from the study of the hippocampus with kainic acid-induced lesions, the kindling model, and other experimental models of epilepsy have demonstrated that seizures induce structural and electrophysiologic alterations in hippocampal pathways that may lead to increased excitability and could play a role in the development and progression of temporal lobe epilepsy. These alterations include mossy fiber synaptic reorganization, induction of NMDA-mediated synaptic transmission, and progressive hippocampal neuronal loss induced by brief kindled seizures. Some of the structural alterations induced by kindling have also been observed in the human epileptic temporal lobe, raising the possibility that mechanisms operative in kindling may play a role in the pathogenesis of hippocampal sclerosis and in the syndrome of human temporal lobe epilepsy. PMID- 2226372 TI - Mesial temporal sclerosis: pathogenesis, diagnosis, and management. AB - Mesial temporal sclerosis (MTS) is probably the most common symptomatic pathologic entity--alone or mixed with other pathologic features--for seizures of temporal lobe origin. The pathophysiology of MTS, including any genetic influence, needs clarification. A characteristic ictal expression for seizures of MTS origin appears not to exist. The majority of patients (78%) with postresection MTS who are seizure-free have tightly localized interictal abnormalities restricted to F7/F8, Sp1/Sp2, T3/T4, and T5/T6 more than 96% of the time. MRI abnormalities may be seen in 55% of patients with MTS if both "hard" and "soft" criteria are used or in 20% when only "hard" criteria are used. The neuropsychologic evaluation of patients with MTS, which includes intracarotid amobarbital test (IAT), may prove to be increasingly useful in identifying patterns of cognitive deficit that correlate with enhancement of both lateralizing and localizing preoperative information. PMID- 2226373 TI - Post-traumatic epilepsy: cellular mechanisms and implications for treatment. AB - Epilepsy complicates severe head trauma. Development of persistent seizures appears to correlate with the extent of trauma. Although early reports suggested that prophylactic administration of antiepileptic drugs would prevent epileptogenesis, controlled studies have failed to corroborate this assumption. Head trauma initiates a sequence of responses that includes altered blood flow and vasoregulation, disruption of the blood-brain barrier, increases in intracranial pressure, focal or diffuse ischemia, hemorrhage, inflammation, necrosis, and disruption of fiber tracts. The presence of an intracranial hematoma has a robust association with the development of post-traumatic epilepsy. Extravasation of blood is followed by hemolysis and deposition of heme containing compounds into the neuropil, initiating a sequence of univalent redox reactions and generating various free radical species, including superoxides, hydroxyl radicals, peroxides, and perferryl ions. Free radicals initiate peroxidation reactions by hydrogen abstraction from methylene groups adjacent to double bonds of fatty acids and lipids within cellular membranes. Intrinsic enzymatic mechanisms for control of free radical reactions include activation of catalase, peroxidase, and superoxide dismutase. Steroids, proteins, and tocopherol also terminate peroxidative reactions. Tocopherol and selenium are effective in preventing tissue injury initiated by ferrous chloride and heme compounds. Treatment strategies for prevention or prophylaxis of post-traumatic epilepsy must await absolute knowledge of mechanisms. Antioxidants and chelators may be useful, given the speculation that peroxidative reactions may be an important component of brain injury responses. However, potential treatment strategies involving gamma-aminobutyric acid (GABA) agonists, NMDA receptor antagonists, and barbiturates need further scientific assessment. PMID- 2226374 TI - The case for a National Association of Physicians for the Environment. PMID- 2226375 TI - In memoriam Norton Nelson. PMID- 2226376 TI - Basic mechanisms leading to focal emphysema in coal workers' pneumoconiosis. AB - Coal miners develop focal emphysema characterized by dilatation of second- and third-order respiratory bronchioles with coal mine dust-laden macrophages infiltrating the wall. A reticulin network with small amounts of collagen and atrophy of smooth muscle occurs. To evaluate the mechanisms of lung injury associated with this lesion, 17 long-term non- or ex-smoking West Virginia underground coal miners underwent bronchoalveolar lavage (BAL) and were compared to healthy nonsmoker and smoker controls. The coal miners had evidence of an alveolar macrophage-neutrophil alveolitis with a significant increase in neutrophils/microliter of epithelial lining fluid and an increased gallium lung scan index (206 +/- 26 units). Alveolar macrophages lavaged from coal miners spontaneously released exaggerated amounts of superoxide anion and hydrogen peroxide in vitro compared to nonsmoking controls. Coal workers had significantly elevated levels of neutrophil elastase in BAL fluid complexed with alpha 1 antitrypsin (P less than 0.01) and normal levels of alpha 1-antitrypsin. An accumulation of activated, dust-laden inflammatory cells with increased release of oxidants and elastase may contribute to the development of focal emphysema identified at postmortem in miners with coal workers' pneumoconiosis. PMID- 2226377 TI - Pathways of human exposure to arsenic in a community surrounding a copper smelter. AB - Several studies have found elevated levels of urinary arsenic among residents living near a copper smelter in Tacoma, Washington. To assess pathways of exposure to arsenic from the smelter, biological and environmental samples were collected longitudinally from 121 households up to 8 miles from the smelter. The concentration of inorganic and methylated arsenic compounds in spot urine samples was used as the primary measure of exposure to environmental arsenic. Urinary concentration of arsenic dropped off to a constant background level within one half mile of the smelter in contrast to environmental concentrations, which decreased more steadily with increasing distance. Among all age-sex-specific groups in all areas, only children ages 0-6 living within one-half mile of the smelter had elevated levels of arsenic in urine. A separate analysis of data for these children suggests that hand-to-mouth activity was the primary source of exposure. Inhalation of ambient air and resuspension of contaminated soil were not important sources of exposure for children or adults. PMID- 2226378 TI - Retention of lead and cadmium in prehistoric and modern human teeth. AB - In 5000-year-old premolars from Nubia and in 500-year-old teeth from Greenland, the lead concentrations were very low; modern teeth contained 10-100 times more lead. In contrast, cadmium concentrations varied by 30-fold in the two prehistorical populations; modern-day cadmium levels were in the lower range of this interval. These data suggest that, when compared to preindustrial exposures, the impact of current environmental lead pollution is considerable, while that of cadmium pollution is much less. PMID- 2226379 TI - Effects of the organophosphorus pesticide fenitrothion on behavior and reproduction in zebra finches. AB - Activity was significantly altered in zebra finch pairs orally dosed with fenitrothion insecticide at rates of 1.04 and 3.80 mg/kg. Both the level and the dirunal pattern of activity were affected. Recovery of normal activity required 1 2 days, depending on the dosage administered. Fenitrothion had only a slight effect on reproduction when parents were dosed at the egg-laying stage of the breeding cycle. The implications of these results for the interpretation of field monitoring studies are discussed. PMID- 2226380 TI - Tetrachloroethene air pollution originating from coin-operated dry cleaning establishments. AB - In 15 coin-operated dry cleaning establishments (CODC), in one building where a CODC had been run and in a private car transporting a dry-cleaned down jacket tetrachloroethene (TCE) indoor concentrations were investigated by air sampling with activated carbon tubes, elution of the carbon with toluene, and subsequent gas chromatographic analysis of the eluate. TCE concentrations in the car transporting the garment were up to 24.8 mg/m3. Within CODC air concentrations between 3.1 and 331 mg/m3 were measured. In the building where a CODC had once been run the TCE concentrations were slowly decreasing after removal of dry cleaning machines. In the basement below the CODC the TCE air concentration was 155 mg/m3 immediately after removal of the machines and 4.5 mg/m3 7.5 months later. TCE migrated from the basement via the staircase to the flats of the second floor where TCE air concentrations were about 1% of the concentrations in the basement. TCE-contaminated building material is shown to be a reservoir causing increased TCE air concentrations for a long time, which is serious considering the carcinogenic and reproductive risks from TCE exposure. PMID- 2226381 TI - Environmental stress and blood glucose change in insulin-dependent diabetes mellitus. AB - Blood glucose (BG) response to psychological stress in insulin-dependent diabetes mellitus (IDDM) patients has not been firmly established. We report a study designed to address the gaps and methodological difficulties reviewed. Subjects with IDDM were exposed to two sessions (12 weeks apart) of two 20-min standardized stressors (active and passive) and a control condition administered in counterbalanced order. To measure BG response, subjects were connected to a glucose/insulin infusion system providing continuous BG measurement. Mood checklist measures were obtained at prestressor, poststressor, and recovery periods. During the first session of testing, the active stressor was associated with significantly more absolute change in BG response than the passive stressor. Results also indicate that IDDM subjects' BG response to this active stressor was idiosyncratic but significantly reliable over time. PMID- 2226382 TI - Psychological stress and blood glucose regulation in type I diabetic patients. AB - Fifteen Type I diabetic patients self-monitored daily mean blood glucose levels (BGL), psychological stress, diet, exercise, and insulin injections for a period of 8 weeks. Separate multiple-regression analyses were conducted for each subject to assess the predictability of BGL from stress reports, independent of the effects of diet, exercise, and insulin self-administration. Considerable individual variability in findings was evident, with stress predicting BGL in a statistically significant manner in 7 of the 15 subjects. Stress had a significant effect on BGL independent of diet, exercise, and insulin administration for each of these 7 subjects. Discussion focused on the problems of measuring the key self-management behaviors influencing BGL and on the possibility that a subgroup of diabetic patients may be BGL stress responders. PMID- 2226383 TI - Impact of stress on objectively recorded menopausal hot flushes and on flush report bias. AB - The hot flush (or flash) is the most widely reported menopausal symptom. Anecdotal reports suggest that women experience more hot flushes when stressed. Although stress may actually trigger hot flushes, another possibility is that women under stress may be more aware of the physiological changes associated with flushes and, therefore, more likely to report them. The goal of this study was to test these hypotheses by investigating the association between stress and both objective (i.e., physiologically recorded) and subjective hot flushes. Twenty-one postmenopausal women who reported having frequent hot flushes each underwent psychophysiological monitoring during stressful and nonstressful laboratory sessions. Significantly more objective flushes were recorded during the stress session than during the nonstress session. The stress manipulation, however, did not affect subjects' propensity to report flushes. These results suggest that the observed association between reported hot flushes and stress is not due to changes in report bias. The physiological mechanisms through which stress may stimulate hot flushes are discussed. PMID- 2226384 TI - Dentists' voice control: effects on children's disruptive and affective behavior. AB - Voice control, a punishment technique based on loud commands, has been used widely in pediatric dentistry. This study examined whether (a) loudness is a necessary component of the technique, (b) voice control actually reduces children's disruptive behavior, and (c) after treatment, children's negative affect increases. Subjects were forty 3 1/2- to 7-year-olds who posed potential behavior problems and who were scheduled for cavity restoration. Children were assigned randomly to either loud- or normal-voice groups. Children who were assigned to either group but who were not disruptive formed a nonexperimental control group. Prior to and after treatment, children reported their feelings using the Self-Assessment Mannequin. Disruptive behavior was scored using the Behavior Profile Rating Scale. Results indicated that, following loud, but not normal voice commands, children reduced their disruptive behavior (p less than .004) and self-reported lower arousal (p less than .09) and greater pleasure (p less than .10). Theoretical and practical implications of these findings are discussed. PMID- 2226385 TI - Analysis of child and parent behavior during painful medical procedures. AB - Examined (a) the impact of demographic, medical, and psychological factors on overall child distress during an invasive medical procedure required for pediatric cancer treatment and (b) the relationship of individual parent behaviors to child distress across phases of the procedure. Seventy 3- to 10-year old pediatric cancer patients receiving outpatient venipuncture and their parents participated. Overall distress was greater in younger children who had fewer previous venipunctures and poorer venous access and whose parents rated them prior to the procedure as less likely to be cooperative. Providing explanations regarding the procedure was the parent behavior most clearly associated with child distress. The impact of parent explanation depended on when the explanation was given and on the child's level of distress at the time. PMID- 2226386 TI - Differential effects of avoidant and attentional coping strategies on adaptation to chronic and recent-onset pain. AB - Examined the effectiveness of attentional and avoidant coping strategies for somatic, behavioral, and psychological adaptation to clinical pain. Subjects were 30 chronic and 30 recent-onset pain patients who used either attentional or avoidant coping strategies in response to their pain. Based on a review of the coping literature, it was hypothesized that subjects with recent-onset pain would demonstrate greater adaptation (lower anxiety, depression, lower pain severity and somatization ratings, and higher levels of social activity) when employing avoidant rather than attentional strategies. Chronic pain subjects using attentional strategies were predicted to demonstrate greater adaptation than chronic pain subjects using avoidant strategies. The results supported this "time x strategy" hypothesis. Implications for pain treatment programs are discussed, and suggestions are made for matching pain duration with patient coping style. PMID- 2226387 TI - Correspondence programs for smoking cessation and weight control: a comparison of two strategies in the Minnesota Heart Health Program. AB - Mailed invitations to participate in weight loss and/or smoking cessation correspondence programs to 31,400 households in a suburban community. Two programs were offered to randomized subsets of households, a 6-month correspondence program costing +5 and the same program for free but requiring a +60 deposit to be refunded based on success in weight loss or smoking cessation. Overall, sign-up included 1,304 people for weight loss and 142 for smoking cessation. The +5 program was about 5 times as popular as the incentive program. Validated weight change after 6 months averaged about 4 lb for the +5 program and 8 lb for the incentive program. Corresponding rates of smoking cessation were about 9% and 20%, respectively. We conclude that correspondence programs for the promotion of weight control and smoking cessation are potentially cost-effective methods for reaching individuals in the community at large, many of whom would not be interested in clinic-based programs. Issues meriting further research include recruitment, especially of smokers, and evaluation of the relative trade offs in recruitment success versus efficacy of differing treatment approaches. PMID- 2226388 TI - Effects of weight cycling on metabolic control in male outpatients with non insulin-dependent diabetes mellitus. AB - Examined the effects of weight cycling (i.e., losing and regaining or gaining and relosing body weight) versus weight maintenance on metabolic control in 327 adult, male, outpatient veterans with non-insulin-dependent diabetes mellitus (NIDDM) who were followed over an average of 3.4 years. When compared with weight maintenance, weight cycling, whether defined as a categorical or as a continuous variable, was not found to be associated with deficits in metabolic control or increased need for hypoglycemic medication. Patients who weight cycled had fasting serum glucose and hemoglobin A1c levels comparable to those who remained within 10% of their initial body weights, and these levels of metabolic control were obtained with similar classes and dosages of hypoglycemic medication. PMID- 2226389 TI - Adherence-health status relationships in childhood diabetes. AB - Used 24-hr recall interviews to assess adherence in a sample of seventy-eight 6- to 19-year-olds with insulin-dependent diabetes mellitus over a 3-month period. Thirteen adherence measures were quantified and grouped into six adherence factors (Injection, Exercise, Diet Type, Testing/Eating Frequency, Calories Consumed, and Concentrated Sweets). Prevailing glucose levels over a 2- to 3 month interval were indexed by glycosylated hemoglobin A1c (HA1c) and glycosylated serum protein (GSP) assays. Fasting triglycerides (TRIG) and total cholesterol (CHOL) assays were used to estimate lipid metabolism. Adolescents were generally less adherent than their young counterparts. Using hierarchical multiple-regression techniques, HA1c and GSP were not reliably predicted by most of the adherence factors; only Calories Consumed showed any predictive power. No significant regression equations emerged for CHOL. In contrast, TRIG was significantly associated with five of the six adherence factors; in all cases, adherence interacted with the patients' metabolic status (as defined by HA1c) at study entry, suggesting that adherence had different effects for youngsters in good versus poor diabetes control. PMID- 2226390 TI - Personal models of diabetes and their relations to self-care activities. AB - Investigated the personal models of diabetes held by 46 female outpatients with non-insulin-dependent diabetes mellitus. The subjects' mean age was 64 years (range = 46 to 79 years), and 24 subjects were taking insulin. Their personal models were explored by using a comprehensive interview including questions on beliefs and emotions about cause, symptoms, course, treatment, and consequences of their diabetes. Two weeks after their interview, patients provided information about their levels of self-care activities, including exercise, diet, and glucose testing. The interview provided multiple indicators of the personal-model constructs from which four composites were formed assessing cause, symptoms, treatment, and seriousness (a combination of course and consequences). In hierarchical multiple-regression analyses, these dimensions significantly improved the prediction of diet level and marginally improved the prediction of exercise after accounting for the effects of age and insulin taking. The results are discussed in terms of variations in personal models across different patient groups and diseases and the role of personal models in determining self-care behaviors. PMID- 2226391 TI - Effects of 24-hour ambulatory blood pressure monitoring on daily activities. AB - Compared the self-monitored activities, locations, and postural positions of 28 hypertensives while they wore an alarm watch and then while they wore a 24-hr ambulatory blood pressure monitor (ABPM) to see if wearing the ABPM led to alterations in behavior. Within the limitations of the study (no counterbalancing of order and twice as many ABPM measures as watch measures), we found significant differences in frequency of being at home or in miscellaneous settings, in standing and reclining positions, and in mental, physical and miscellaneous activities between the two occasions. PMID- 2226392 TI - The equine stress response to anaesthesia. PMID- 2226393 TI - The human stress response to surgical trauma and anaesthesia. PMID- 2226394 TI - New insights into the equine respiratory tract. PMID- 2226395 TI - Atelectasis causes gas exchange impairment in the anaesthetised horse. AB - The anatomical basis of gas exchange impairment in the anaesthetised horse was studied by computerised tomography (CT; three shetland ponies) and morphological analysis (one pony and three horses). By means of CT, densities were seen in dependent lung regions early during anaesthesia, both with spontaneous breathing and with mechanical ventilation. The densities remained for some time where they had initially been created when the animal was turned from dorsal to sternal recumbency. Deep insufflation of the lungs reduced the dense area. Gas exchange was impaired roughly in proportion to the dense area. On histological analysis, the densities were atelectatic and congested with blood. Gravimetry showed no more extravascular water per unit lung tissue in the atelectatic than in the 'normal' regions, and the blood content was increased only slightly. It is concluded that the horse develops atelectasis in dependent lung regions early during anaesthesia in dorsal recumbency, and that atelectasis is the most likely explanation for the large shunt and impaired arterial oxygenation regularly seen during anaesthesia. PMID- 2226396 TI - Agenesis of the corpus callosum with cerebellar vermian hypoplasia in a foal resembling the Dandy-Walker syndrome: pre-mortem diagnosis by clinical evaluation and CT scanning. PMID- 2226397 TI - A scanning electron microscopic study of the equine upper respiratory tract. AB - The surface features of the upper respiratory tract of 20 clinically normal horses of various ages and types were studied with scanning electron microscopy. In the rostral part of the nasal cavity, there was a wide zone of non-ciliated epithelium whereas, caudally, the surface was well ciliated. This latter type of epithelium extended into the nasopharynx and guttural pouches although scattered areas of non-ciliated microvillous cells were also found. PMID- 2226398 TI - An ultrastructural study of the equine lower respiratory tract. AB - The surface features of the lower respiratory tract of 20 clinically normal horses of different ages and types were studied with scanning electron microscopy. Parallel light microscopical and transmission electron microscopical studies were also carried out. The ciliary carpet was virtually complete from the trachea to the lobar bronchi. In small bronchi, ciliation was less complete allowing numerous non-ciliated mucous cells to become obvious. The terminal bronchioles, populated mainly by non-ciliated bronchiolar epithelial cells, had an abrupt junction with alveolar ducts. Interalveolar pores were common particularly in older horses. PMID- 2226399 TI - Ultrastructural findings in horses with chronic obstructive pulmonary disease (COPD). I: Alterations of the larger conducting airways. AB - Extensive light and electron microscope studies of the conducting airways were carried out in 28 horses with varying degrees of clinically manifested chronic obstructive pulmonary disease (COPD) and in 8 horses with normal lungs. The principal ultrastructural changes were found in the ciliated cells. There was focal loss of ciliated cells, which were replaced by undifferentiated cells in a largely hyperplastic epithelium, and some horses, independent of the degree of severity of the disease, showed various types of ciliary malformation. The finding of dilated intercellular clefts and accumulations of mast cells was interpreted as morphological evidence of non-specific mucosal hyperreactivity. Interstitial cells with intracytoplasmal crystal inclusions, the cause of which is not clear, were seen in many horses. Comparison between the clinical diagnosis and the morphological findings showed partial correlation. The ciliary loss, the appearance of peribronchial inflammatory processes and the occurrence of intracytoplasmic crystalline inclusions showed a positive correlation. In 12 of 28 cases, the severity of clinical diagnosis agreed with the degree of the morphological findings. The changes in the conducting airways were interpreted pathogenetically as reactive processes to changes in the small airways in the course of equine COPD. PMID- 2226400 TI - Ultrastructural findings in horses with chronic obstructive pulmonary disease (COPD). II: Pathomorphological changes of the terminal airways and the alveolar region. AB - Extensive light and electron microscope studies (transmission and scanning electron microscopy) of the bronchioles and alveolar region, in 28 horses suffering chronic obstructive pulmonary disease (COPD) and eight control horses, revealed good correlation between clinical severity and morphological changes. In the bronchiolar epithelium the non-ciliated bronchiolar epithelial (Clara) cells, in particular, showed ultrastructural alterations and, even in the mild stages of disease, these presented degenerative changes and lack of differentiation. Together with loss of granulation in the Clara cells and metaplasia of the goblet cells, cells were seen with unusual intracytoplasmic lamellar inclusion, the number of which increased sharply with clinical severity. The focal changes in the alveolar region were necrosis of type I epithelial cells, alveolar fibrosis of varying degrees with type II epithelial transformation and emphysema or hyperinflation, with an increase in Kohn's pores. Some horse also showed morphological signs of interference with the surfactant system, in the form of marked cysts with lamellar structure. The alveolar changes were mostly in the peribronchiolar region and were, therefore, interpreted as reactive processes. No conclusions as to the aetiology of equine COPD can be derived from these morphological investigations. PMID- 2226401 TI - The influence of photoperiod on gonadotrophin-releasing hormone stimulated luteinising hormone release in the anoestrous mare. AB - The transition from anoestrus to oestrus in mares is controlled by photoperiod. The present study examined whether additional daylength would accelerate the mares' response to gonadotrophin-releasing-hormone (GnRH). Nine anoestrous mares were placed under ambient or artificial long lighting on 7th January. The four month experimental period was divided into a three-day sequence which was repeated at 21 day intervals. Ovaries were palpated rectally on Day 1; saline was injected (1 ml intravenously [iv]) on Day 2; GnRH was administered (0.59 microgram/kg bodyweight iv) on Day 3. Blood was taken at -60, 0, 15, 30, 60 and 120 mins relative to saline or GnRH treatment. Serum luteinising hormone (LH) was determined by a homologous equine radioimmunoassay (RIA). Several criteria were employed to define a positive response to GnRH and the results were analysed by Fisher's exact probability test. Treatment with artificial light allowed a response to GnRH within six weeks whereas the mares in ambient lighting took 12 weeks to respond to GnRH. The advancement in the time of response to GnRH under the long photoperiod could be related to changes in pituitary LH content, accelerated follicular activity or alterations in other brain-pituitary hormone levels. PMID- 2226402 TI - Peritoneal fluid values from healthy foals. AB - Peritoneal fluid was analysed from 17 foals, aged 13 to 134 days with a mean age of 68 days. Cytologically, the peritoneal fluid was characterised by a mean total cell count of 0.45 x 10(9)/litre (range 0.06 to 1.42 x 10(9)/litre), rare eosinophils, rare cytophagia and variable percentages of neutrophils and mononuclear cells. These data indicate that peritoneal fluid nucleated cell counts over 1.50 x 10(9)/litre in the foal should be interpreted as elevated. Biochemical evaluation revealed a mean biuret protein level of 12 g/litre, mean refractive index protein level of 16 g/litre and urea nitrogen concentration of 1.96 mmol/litre. There was no correlation between the foals' white blood cell and peritoneal fluid nucleated cell counts. Results of this study indicate that adult horse reference values for evaluation of peritoneal fluid are of questionable validity for foals. Diagnostically, the most important observation was that maximum peritoneal fluid nucleated cell counts in healthy foals were much lower than reported maximal reference values for adult horses (1.5 x 10(9)/litre versus 5.0 x 10(9)/litre or 10.0 x 10(9)/litre). PMID- 2226403 TI - Plasma histamine levels during exploratory laparotomies in suspected equine grass sickness cases. PMID- 2226404 TI - The crystalline composition of normal equine urine deposits. PMID- 2226405 TI - An autoradiographic study of equine hoof growth. PMID- 2226406 TI - Soft palate cysts as a cause of pharyngeal dysfunction in two horses. PMID- 2226407 TI - Serum protein changes in four horses with monoclonal gammopathy. PMID- 2226408 TI - Sequence analysis of proteins separated by polyacrylamide gel electrophoresis: towards an integrated protein database. AB - Improved technologies or the synergistic use of complementary methods enhance the efficiency of research and permit the exploration of new approaches for the investigation of complex problems. High sensitivity protein sequence analysis and polyacrylamide gel electrophoresis are such complementary methods. Here we summarize the current status of high sensitivity sequence analysis of proteins separated in polyacrylamide gels and discuss strategies by which this technology can enhance biological research by generating new approaches for the solution of complex, multifacetted problems. Finally, we outline imminent technological advances in the area of high sensitivity protein sequence analysis and argue that further technological developments will ultimately lead to the generation of an integrated protein database (containing structural and functional as well as physiological information in an easily accessible form) of all the proteins separated by high resolution two-dimensional gel electrophoresis. PMID- 2226409 TI - Internal sequence analysis of proteins separated on polyacrylamide gels at the submicrogram level: improved methods, applications and gene cloning strategies. AB - The fields of protein chemistry and molecular biology are currently merging for study of biologically relevant events and conditions. To obtain partial sequences of microamounts of protein, efficient integration of high resolution separation and sequencing technologies is required. We report here on improved methods that allow extensive internal sequencing of 10 to 20 picomoles protein recovered from one- or two-dimensional gels. Each step of the standard protocol of Aebersold et al. (Proc. Natl. Acad. Sci. USA 1987, 84, 6970-6974) and the required instrumentation were examined and specifically adapted for use with submicrogram amounts of protein. Optimizations of in situ microdigests and liquid chromatography were needed for improved peptide recovery. Subsequent automated sequencing required subpicomole analysis. New methods for S-alkylation of gel separated proteins and accurate identification of tryptophan-containing peptides were introduced to insure overall higher efficiencies. The acquired internal sequences facilitated cloning of the genes and several strategies are discussed. Applying our method, several proteins of unknown structure were sequenced and successfully identified or cloned. Internal sequences of submicrogram protein amounts, recovered from a single two-dimensional gel of Escherichia coli total protein (120 micrograms), allowed unambiguous identification of the spots but pre gel enrichment will be required for analysis of most (90-95%) other spots. Integration of comprehensive two-dimensional gel protein databases with methods and strategies outlined here could potentially be an abundant source of DNA probes and markers useful for guidance of the human genome sequencing project and for analysis of the emerging vast amounts of data. PMID- 2226410 TI - Combination of two-dimensional gel electrophoresis with microsequencing and amino acid composition analysis: improvement of speed and sensitivity in protein characterization. AB - High-resolution two-dimensional polyacrylamide electrophoresis (2-DE) is commonly used as an analytical approach to resolve and detect most of the numerous protein species of an organism. However, the isolation of microgram amounts of protein in a 2-DE spot in a form suitable for microsequence analysis and amino acid composition analysis is a key step in the chemical characterization of these proteins. With the development of chemically inert membranes it is now possible to retain proteins present in low quantities from the polyacrylamide matrix with high yields. The immobilized proteins are suitable for direct sequence analysis and amino acid composition analysis. The combination of protein chemical and electrophoretic techniques makes it possible to obtain chemical information from subpicomole quantities of protein, resulting in the availability of a new set of biologically important proteins for structural analysis. This paper summarizes the methods and strategies for the chemical protein analysis of 2-DE spots in our laboratory. PMID- 2226411 TI - Protein blotting followed by microsequencing. AB - The use of new membranes such as activated or derivatized glass fibers as well as synthetic membranes, which are compatible with the hazardous sequencing reagents, are described. Precautions to be taken in order to prevent N-terminal blockage of the proteins during electrophoresis and blotting are described, as well as the conditions for protein detection after blotting and protein treatment for in situ amino acid analysis, fragmentation and microsequencing. For a number of standard proteins and bacterial ribosomal proteins microsequence analysis is reported for two commercially available sequencers (Applied Biosystems and Knauer). PMID- 2226412 TI - Electroblotting of polypeptides onto glass fiber filters for direct sequence analysis after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AB - The technique of electroblotting polypeptides onto Polybrene-treated glass fiber filter discs after protein detection with potassium chloride is evaluated further with different proteins in separate applications. The number of proteins analyzed with this method is now more than double that previously reported. Reproducible results in good yield are obtained. Average overall yield--including the electrophoretic step before blotting--is 26%, with maximal recoveries through all steps up to 60%. High sensitivity radiosequence analysis is also applicable. Recent modifications of the previously described procedure include use of Whatman glass fiber filters, removal of air in the Polybrene-impregnated filters by buffer penetration under reduced pressure, and use of widely different times for electrotransfer. Special advantages with this method are low extent of protein alpha-amino group destruction, direct use of the entire filter in the sequencer, and insensitivity to variations in electroblotting time. Gas-phase hydrolysis in situ of blotted proteins followed by amino acid analysis is known to give a low yield of polar amino acids, and often artifacts, but can still give an estimate of the amount of polypeptide immobilized on the filter. A wash with n-butyl chloride is now shown to reduce the Polybrene-associated artifacts, and an addition of sodium chloride to increase the recovery of polar amino acids. These two steps therefore appear interesting in schemes for compositional analyses of electroblotted proteins. PMID- 2226413 TI - Microsequencing of proteins electrotransferred onto immobilizing matrices from polyacrylamide gel electrophoresis: application to an insoluble protein. AB - Semidry electroblotting is convenient and allows a rapid and efficient protein transfer from one- or two-dimensional polyacrylamide gels onto sequencer stable supports for protein microsequence analysis in a gas-phase sequencer. Using this technique, we determined the amino acid sequences of the basic 7S globulin (Bg), an insoluble protein present in soybean seeds. Based on sequence determination, the cDNA-encoding Bg could be easily cloned and characterized. PMID- 2226414 TI - Blotting efficiency investigated by using two-dimensional electrophoresis, hydrophobic membranes and proteins from different sources. AB - Purification and chemical characterization of proteins may be achieved by combining two-dimensional electrophoresis (2-DE) and microsequencing or amino acid analysis. To enable this combination, the protein has to be transferred as completely as possible from the gel into the sequencer. In this study hydrophobic membranes were used as support for the transfer and proteins were transferred from the gels onto the membranes by semidry blotting. Blotting conditions were optimized to obtain high blotting efficiencies for as many proteins of a complex 2-DE pattern as possible. Under optimized conditions, blotting efficiencies between 60% and 100% were obtained for five marker proteins; the mean values from four regions of a 2-DE pattern from 29 unknown proteins of a complex protein mixture from mouse brain were between 60% and 79%. The four commercially available hydrophobic membranes that were compared showed only slight differences in protein amount on the membranes after blotting for whole protein patterns, whereas single proteins occurred with higher amounts on either one or the other membrane. The results of the blotting optimization allowed us to suggest a blotting mechanism with which systematic improvement of the blotting conditions is possible for problematic proteins. PMID- 2226415 TI - Identification of rat liver glutathione S-transferase Yb subunits by partial N terminal sequencing after electroblotting of proteins onto a polyvinylidene difluoride membrane from an analytical isoelectric focusing gel. AB - Rat liver glutathione S-transferases were partially purified using S-hexyl glutathione affinity chromatography, followed by native isoelectric focusing employing a pH 7-11 or pH 3-10 gradient. Proteins were excised and eluted from the gel for determination of subunit composition using sodium dodecyl sulfate polyacrylamide gel electrophoresis. In separate experiments, isoelectric focusing gels were equilibrated with a sodium dodecyl sulfate-containing buffer at high pH, and proteins on the gel were electroblotted onto a polyvinylidene difluoride membrane, utilizing graphite plates as electrodes. The membrane-bound proteins were visualized by Coomassie Brilliant Blue staining. The protein bands were then excised from the membrane and inserted into a gas phase sequenator for direct sequencing. N-Terminal sequences thus determined were compared with published cDNA sequences. The isoelectric points (pIs) and positions on the isoelectric focusing gel of Yb1Yb1, Yb1Yb2 and Yb2Yb2 subunits were determined. We have also located on the pH 3-10 focusing gel an N-terminal blocked glutathione S transferase which has a molecular weight similar to Yb subunits. PMID- 2226416 TI - Ergonomic aspects of the health and safety of VDT work in Japan: a review. PMID- 2226417 TI - New electronic media and the human interface. AB - Discussion is focused on the relationship between the new media and the human visual system. First, the process of information transmission in the human visual system is shown as a hierarchically structured model. Second, examples of the human interface in the development of a Japanese teletext system are shown, such as desired luminance and contrast, or favourable colour combination, or how to make superimposed sentences on screen easy to read. Third, examples of the human interface in the development of Hi-Vision, or High Definition Television (HDTV), are discussed, namely the conditions required for Hi-Vision from the standpoint of visual characteristics, the visual effects of Hi-Vision, and an objective evaluation of psychological effects of Hi-Vision. PMID- 2226418 TI - CRT display visibility in automobiles. AB - Three experiments were carried out into aspects of CRT display in the context of driving automobiles. The first focused on the combination of colours which renders information 'easy-to-read', and determined the relationship between luminance contrast and chromaticity difference. In the second a background luminance which was not dazzling at night was expressed in a chromaticity diagram. In the third the amount of information which can be read 'at-a-glance' was investigated. PMID- 2226419 TI - The ergonomic evaluation of eye movement and mental workload in aircraft pilots. AB - This paper presents an experiment which examines characteristics of pilots' scanning behaviour when using integrated CRT displays, and the changes in characteristics when pilots face abnormal situations. The subjects were five experienced pilots. They performed two modes of flight tasks, under normal and abnormal situations, in flight simulators with standard settings. The flight simulators were for a Boeing 747-300 (B747), which made use of electromechanical displays, and for a Boeing 767 (B767), equipped with integrated CRT displays. The results showed that the B767 pilots tended to gaze at the attitude director indicator which was displayed in the integrated CRT display. It was assumed that 'gaze-type scanning' might be one of the characteristics of pilots' scanning behaviour in cockpits which use the integrated display. By employing subjective ratings and heart rate variability to measure mental workload, no differences in mental workload between the B767 pilots and the B747 pilots were observed. However, in abnormal situations, the changes in scanning pattern for B767 pilots were found to be smaller than those of the B747 pilots. It is concluded that the application of integrated displays helps pilots to obtain sufficient information more easily than electromechanical displays do, even under abnormal situations. PMID- 2226420 TI - Examination of the near triad in VDU operators. AB - It has recently been demonstrated that the tonic level of accommodation is related to the loading of accommodative work. The aim of the present study was to investigate the effect of a sustained accommodative stimulus on the tonic level of accommodation, pupil, and convergence, i.e., the near triad, in three different groups of young (20-39 years) subjects, viz., 1. 19 professional visual display unit (VDU) workers; 2. 12 ordinary hard copy (non-VDU) workers; and 3. 19 control subjects doing different jobs from the two former groups. All had worked 25-30 h per week for over two years. Only Groups 1 and 2 had eyestrain after office work. Except for mild myopia, subjects had no eye or systemic disease upon routine examination. Accommodation was measured with an objective infrared optometer, the pupil was measured by an infrared video pupillography, and convergence was measured from the contralateral eye by photoelectronic oculography. In order to elicit tonic responses, the velocity of the target stimulus was 0.2 D (diopters) per second. Based on the data obtained from the controls, the near triad was analysed. Asymmetric response of the near triad in the right and the left eye and the existence of a hysteresis curve, especially in the pupil and in convergence, were the major findings. No abnormality was found in the control group. In the VDU group, 34.6% showed an abnormal near triad, but this also occurred in 18.5% of the non-VDU group. Even with the same complaint of eyestrain, it was concluded that VDU work produced abnormalities 1.8 times higher in the near triad produced by tonic stimulus. PMID- 2226421 TI - Study of the relationship between lacrimation and blink in VDT work. AB - VDT (Visual Display Terminal) work generates various symptoms in operators' eyes such as strain, a sensation of dryness, the presence of a foreign body, and so on. Research suggests that lacrimal abnormality may be related causally to such symptoms. In this paper, the relationship between lacrimation (the secretion of tears) and the frequency of blink due to VDT work in health subjects and VDT workers with such symptoms, and consequent therapeutic methods, were studied. When lacrimation, BUT (Break-UP Time), and the frequency of blink before and after VDT work compared in the control subjects and VDT-operators, an essential difference was noted in experiment 1 the frequency of blink decreased only during VDT operation, and a decreasing tendency of lacrimation was also noted while lacrimation before operation was already less in the VDT group; no large variation was noted before or after VDT operation. The frequency of blink was relatively high during operation, and a decreasing tendency of BUT was noted, compared with that for control subjects. In experiment 2, lacrimation increased remarkably in four eyes (of two operators), and relief from the subjective symptoms was noted. However, BUT intactly reduced similarly before the use of a gelatin rod during the whole process. The insertion of a gelatin rod was consecutively carried out every two weeks for approximately eight months; the development of complications such as dacryosolenitis, etc., was not noted. From these results, it is considered that the insertion of a gelatin rod is clinically useful for VDT operators with decreasing lacrimation. PMID- 2226422 TI - An ergonomic evaluation of lens accommodation related to visual circumstances. AB - This study is intended to make clear the relationships between a number of external conditions (target luminance, size, etc.), dynamic responsiveness of the lens accommodation, and microfluctuation. Further, the effects of ageing and the difference between monocular and binocular observations are examined. These studies established that age factors have a large bearing on the ability of the lens to focus on an object, as well as affecting such abilities as the responsiveness of the lens accommodation, amplitude of lens accommodation response, microfluctuation, and contraction and relaxation time. Of these accommodation functions, such factors as contraction and relaxation time clearly reflect the ease of seeing an object. Clear relationships between the amount of diopter and the ease of seeing an object were also observed. Further, it was established that a binocular observation is more responsive (velocity of contraction) than a monocular one. As to the microfluctuation, on the other hand, clear effects of age on its spectrum distribution were recognized but no definite correlations concerning the ease of seeing an object were observed. PMID- 2226424 TI - The acceptable load while marching at a speed of 5 km h-1 for young Chinese males. AB - Ninety-three young Chinese men selected at random were involved in the load carrying experiments. They marched at 5 km h-1 carrying loads of 0, 15, 20, 25 and 31 kg for 7 h per day. At this speed the acceptable load to be carried was 20 kg. Under this load 95% of the men had heart rates below 120 bt min-1 while marching and energy metabolism was in balance. Nevertheless, 10-15% of the men were fatigued and felt tired. PMID- 2226423 TI - Maximum acceptable repetitive lifting workload by Chinese subjects. AB - This study used psychophysical methods to determine the acceptable mean maximum lifting workload for eight Chinese young male subjects, and examined the effects of lifting technique (including freestyle, stoop and squat), lifting frequency (including 2, 3, 4, 5 and 6 lifts/min) and physical characteristics on the maximum acceptable workload. The results are described as follows: (1) The maximum acceptable weights selected by subjects varied from 11.34 to 18.33 kg with changes in lifting technique and frequency. These data were lower than those previously obtained; (2) The upper limit of physiological tolerance over an 8 h workday was also generally lower than previously suggested. However, this upper limit varied with changes in lifting technique and frequency, and in some circumstances it was the same as or even higher than previous limit; (3) Lifting efficiency was affected significantly by technique and frequency. The rank order of efficiency for three lifting techniques were freestyle, stoop and squat. Efficiency was greatest when lifting frequency was between 5 and 6 lifts/min; and (4) The correlations between the maximum acceptable workloads selected by subjects and anthropometric sizes were significant, but those between maximum acceptable workload and isometric strength were not. PMID- 2226425 TI - The effects of VDT data entry work on operators. AB - The before/after study of physiological and biochemical parameters was used to delineate the effects of VDT data entry work on operators. Twenty-nine healthy Chinese students were chosen and divided at random into the simple and the complicated data entry group. The subjects were instructed to work as quickly and correctly as possible according to the 'Data Entry Work Programme' for 150 min. Work performance (correct entry) was automatically recorded once every 10 min. The before/after parameters were tested respectively. The results showed that performance fluctuated over time. It decreased obviously after 50-60 min of work, followed by a rebound, and there was a terminal motivation phenomenon at the end of the test, which was associated with the auto-arousal and cerebral compensatory effort. Changes in physiological parameters revealed that operators were fatigued after data entry work. The adrenaline excretion in urine showed a tendency to increase after simple data entry work. The noradrenaline excretion showed a tendency to decrease after complicated data entry work. The differences in performance, diastolic blood pressure in a standing position and neurobehaviour between two groups indicated that much stress was experienced when performing complicated data entry work. PMID- 2226426 TI - A three-dimensional ultrasonic system for posture measurement. AB - A time-efficient, cost-effective, and accurate system has been developed for measuring static three-dimensional joint coordinates in the laboratory. This system uses a personal computer interface to determine the distance between transmitters positioned at body joints and receivers positioned near the subject by measuring the travel time of ultrasound. Distance data are then converted to spatial coordinates and joint angles. The system can determine the location of 14 joints at one time. An experiment using three distances and five orientations between a transmitter and a receiver was performed to investigate the significance of measurement errors for the new system. The results showed that the standard deviation of the distance measurement was about 0.2 cm for single orientation conditions and was about 1 cm for all conditions tested. A second experiment using 11 transmitters and four receivers was performed to investigate the significance of measurement errors when determining three-dimensional coordinates. The results showed no significant difference between actual and measured coordinates. The system was then used to study the posture of a subject's upper extremity. Eight postures representing a variety of typical reaching tasks were examined. The results showed that the system was suitable for three-dimensional posture measurement. PMID- 2226427 TI - Physical work and strain involved in manual sorting of postal parcels. AB - A field study was conducted to assess cardiorespiratory and musculoskeletal stress and strain and work output during manual sorting of postal parcels, and to detect the effects of parcel sorting on the maximal muscle strength and endurance. The volunteer subjects comprised 32 healthy male sorters with mean (+/ s.d.) age of 34 +/- 7 years at five different sorting sites. Each subject was studied during one evening work shift. During the shift of 391 +/- 46 min the subjects manually sorted 1173 +/- 630 parcels and walked 4.7 +/- 2.3 km with and without the load. While sorting, heart rate was 101 +/- 18 beats min-1. In the heaviest tasks the oxygen consumption was 1.2 +/- 0.41 min-1, and no elevated blood lactate concentrations were found. Work postures in which the back was bent forward averaged 24% of the time for sorting. The overall cardiorespiratory rating and local ratings of perceived exertion for arms, back, and legs did not exceed the 'somewhat strong' level during the work shift. The maximal static strength both for the right and left hand-grip muscles was, on average, 3% lower (p less than 0.05) after the work shift than before the shift. No significant differences were found in the static or dynamic endurance times for the hand-grip muscles when the results obtained after the work shift were compared to the baseline values. At sorting centres the stress and strain on the cardiorespiratory and musculoskeletal system was evaluated to remain within acceptable limits for healthy male sorters. PMID- 2226428 TI - Influence of simultaneous bilateral exertion on muscle strength during voluntary submaximal isometric contraction. AB - The influence of simultaneous bilateral exertion on muscle strength was tested under the conditions in which the same or different levels of strength were exerted by the right and left arm (or hand). Isometric muscle strength of elbow flexion, elbow extension and hand grip was studied. Subjects voluntarily exerted 25%, 50%, and 75% of maximal strength based on their subjective judgement without the feedback of the strength actually exerted. Involuntary decrements of muscle strength were caused by the bilateral exertion. Muscle strength of both sides decreased under the condition where the same level of strength was exerted by the right and the left arm (or hand). When different levels of strength were exerted by each arm (or hand), the strength of the weaker side considerably decreased, while the strength of the stronger side did not decrease. PMID- 2226429 TI - Musculo-skeletal symptoms and signs and isometric strength among fishermen. AB - Previous studies have shown that subjective symptoms from the musculo-skeletal system are common among fishermen. In the present study, physical signs of malfunction were also found to be common in this profession. The co-existence of physical signs and subjective symptoms differed greatly between different joint systems, and the correlation was in some locations very low. The prevalence of physical health problems other than orthopaedic problems was low. Isometric lifting strength was high compared to results reported on other vocational groups. PMID- 2226430 TI - A multinuclear magnetic resonance study of a cls11 mutant showing the Pet- phenotype of Saccharomyces cerevisiae. AB - Energetic and intermediary metabolism was studied in a Pet- mutant of Saccharomyces cerevisiae with a calcium-sensitive phenotype that shows an inability to grow when cultured in a medium containing non-fermentable substrates. The perchloric acid extracts were prepared from suspensions of cls11 mutant and wild-type cells incubated with [1,3-13C]glycerol or [2-13]acetate, and analyzed by 31P, 13C and 1H NMR. 31P- and 1H-NMR spectra showed significant differences between cls11 and wild-type cells at the level of amino acids, the storage carbohydrate trehalose (higher in mutant cells), and sugar phosphates (higher in wild-type cells). 13C-NMR spectra revealed major differences in the steady-state labelling of glutamate carbons. For incubations with [1,3 13C]glycerol, we estimated from the relative 13C enrichment of glutamate carbons that acetyl-CoA C2 is 43% C13 labelled in wild-type and 10% 13C labelled in mutant cells, respectively. For incubations with [2-13C]acetate, we calculated that the ratio of the relative flux through the glyoxylate shunt versus oxidative reactions is 58% in wild-type cells and 44% in the cls11 mutant cells. Again, a dilution of the relative enrichment of C2 of acetyl-CoA was observed in the mutant cells (89%) compared to the wild-type cells (97%). These results are discussed in terms of pleiotropic defects in non-fermentable carbon metabolism in mutant cells. PMID- 2226431 TI - A natural-abundance 13C-NMR study of Dictyostelium discoideum metabolism. Monitoring of the spore germination process. AB - Amoebae and spores of the cellular slime mold Dictyostelium discoideum have been investigated by natural-abundance proton-decoupled 13C-NMR spectroscopy. Axenically grown vegetative amoebae have been found to contain, as prominent metabolites, the polyamines 1,3-diaminopropane (3.2 mM), putrescine (9.4 mM) and spermidine (1.7 mM). We also detected lactic acid (4.4 mM) and the following amino acids as free metabolites in concentrations ranging over 1-3 mM: glycine, alanine, glutamine and glutamate. The glycogen level is highly dependent upon growth state, being below the level of NMR detection in early-exponential cells and reaching about 110 mM glucose equivalents in plateau-phase cells. Dormant spores contained high amounts of trehalose (50 mM), glutamine (73 mM) and glutamate (20 mM). The latter two compounds were not reported previously to be present in such high concentrations in Dictyostelium spores. Germination induced by heat-shock activation was monitored by 13C NMR. No change in the major components occurred during the activation step. The progressive disappearance of trehalose during germination correlated with the decrease of glutamine and glutamate. In general, the data suggest that germinated spores contain a composition of free metabolites very similar to that of starved vegetative amoebae. PMID- 2226432 TI - Muscle-specific response to thyroid hormone of myosin isoform transitions during rat postnatal development. AB - Transitions from embryonic and neonatal to adult-type-II isomyosins are known to be related to the increase in the thyroid hormone plasma concentration during postnatal development. These transitions have been shown, however, to occur at different times, depending on the muscle, suggesting that each muscle responds differently to the thyroid hormone. We have investigated quantitatively the effects of experimental hypothyroidism and hyperthyroidism on isomyosin transitions from birth until the 45th postnatal day in eight rat muscles: diaphragm, intercostals, gastrocnemius medialis, soleus, plantar muscles of the foot, tongue muscle, levator ani and bulbocavernosus complex, and masseter. Hypothyroidism delayed the isomyosin transitions in all the muscles examined, particularly in the sexually dimorphic muscles (levator ani and bulbocavernosus complex and masseter). However, it did not eventually inhibit isomyosin transitions, indicating that the thyroid hormone was not an absolute requirement for these to occur. Hyperthyroidism had only a slight effect on isomyosin transition in the diaphragm, and accelerated such transitions in the other muscles. The transition curves of all the muscles investigated, except those of the sexually dimorphic muscles, became similar to that of the diaphragm, demonstrating that the various muscles did not display the same sensitivity to the thyroid hormone but were regulated by it in the same way. The isomyosin transitions in the sexually dimorphic muscles remained late in comparison to that in the diaphragm, which suggests a more complex regulation. The effect of hyperthyroidism was not permanent and could be reversed, by interruption of the treatment, to a greater or lesser extent depending on the muscle. In all muscles containing slow-type-I isomyosin, hypothyroidism had no effect on this isomyosin synthesis, whereas hyperthyroidism inhibited it. This inhibition ceased rapidly after the interruption of the treatment. PMID- 2226433 TI - Hormone binding to natural mutants of human serum albumin. AB - High-affinity binding of progesterone, testosterone, prostaglandin F2 alpha and L thyroxine to five genetic variants of human serum albumin with defined point mutations was investigated by equilibrium dialysis (pH 7.4). Endogenous albumin A (Alb A) from each individual and commercial human serum albumin were used as controls in each case. The association constant for binding of progesterone to Alb Canterbury (Lys313----Asn) was 1.5 times that calculated for binding to the corresponding, endogenous Alb A. In contrast, the variants Alb Niigata (Asp269--- Gly), Alb Roma (Glu321----Lys), Alb Parklands (Asp365----His) and Alb Verona (Glu570----Lys) all had normal progesterone binding properties. Specificity with respect to the type of mutation was also found for the binding of testosterone and prostaglandin F 2 alpha. Testosterone binding to Alb Roma was only 0.7 of that determined for endogenous Alb A, whereas prostaglandin F 2 alpha binding to Alb Niigata was increased by a factor 2.4. In the case of L-thyroxine normal binding properties were found for all the variants. Steric effects and/or conformational changes of the protein, introduced by the amino acid substitutions, probably account for the altered hormone binding. However, in the case of the increased binding of prostaglandin F2 alpha to Alb Niigata electrostatic effects could also be involved. The experimental findings suggest different high-affinity sites for the four hormones. Progesterone, testosterone and prostaglandin F2 alpha are apparently bound within the middle third (domain II) of the protein molecule. The possible position of the primary L-thyroxine site is discussed. PMID- 2226435 TI - A glycoprotein inhibitor of pectin methylesterase in kiwi fruit (Actinidia chinensis). AB - The finding of a powerful inhibitor of pectin methylesterase in ripe kiwi fruit is reported. The inhibitor was revealed to be a glycoprotein. It was purified to homogeneity and found to have a molecular mass of about 28 kDa, as estimated by gel filtration chromatography, SDS/PAGE and analytical ultracentrifugation. The sugar portion is composed of galactose, arabinose and rhamnose, the latter being much less represented. The amino acid composition showed a very high content of acidic residues compared to basic ones, which is the reason for the very low isoelectric point of the protein (less than 3.5). The kind of inhibition on kiwi pectin methylesterase was found to be competitive with an apparent Ki of 0.22 microM, using citrus pectin as a substrate. Moreover, the inhibitor is effective in inhibiting pectin methylesterase in the pH range 3.5-7.5. Kiwi inhibitor appears to be specific for pectin methylesterase, inasmuch as it was found to be ineffective against other polysaccharide-degrading enzymes, such as polygalacturonase and amylase. Conversely, it appears to be completely aspecific as far as the pectin methylesterase source is concerned. In fact, it was found to inhibit this enzyme effectively from all the sources we assayed, i.e. orange, tomato, apple, banana, potato. PMID- 2226434 TI - Geometry of binding of the benzamidine- and arginine-based inhibitors N alpha-(2 naphthyl-sulphonyl-glycyl)-DL-p-amidinophenylalanyl-pipe ridine (NAPAP) and (2R,4R)-4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulphonyl)-L arginyl]-2-piperidine carboxylic acid (MQPA) to human alpha-thrombin. X-ray crystallographic determination of the NAPAP-trypsin complex and modeling of NAPAP thrombin and MQPA-thrombin. AB - The X-ray crystal structure of the trypsin complex formed with N alpha-(2 naphthyl-sulphonyl-glycyl)-DL-p-amidinophenylalanyl-piper idine (NAPAP) was determined with X-ray data to 0.18-nm resolution and crystallographically refined. NAPAP binds into the active site of trypsin in a quite compact form: the p-amidinophenylalanine moiety of the D-stereoisomer binds into the specificity pocket; the glycyl group is hydrogen bonded with Gly216; the naphthyl group stands perpendicular to the indole moiety of Trp215; the piperidine ring is tightly packed between this naphthyl moiety and His57; in consequence the carboxy terminal amido bond of NAPAP is located in such a way that it is not susceptible to the active-site Ser195. NAPAP and (2R,4R)-4-methyl-1-[N alpha-(3-methyl 1,2,3,4-tetrahydro-8- quinolinesulphonyl)-L-arginyl]-2-piperidine carboxylic acid (MQPA) [Matzusaki, T., Sasaki, C., Okumura, C. & Umeyama (1989) J. Biochem. (Tokyo) 105, 949-952] were transferred in their trypsin-binding conformations to human alpha-thrombin [Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S. R. & Hofsteenge, J. (1989) EMBO J. 8. 3467 - 3475] and energy minimized. Both synthetic inhibitors fit perfectly into the much more restricted active site of thrombin. The accommodation of the S-aryl moieties in the 'aryl-binding site' and of the piperidine rings in the S2 subsite of thrombin are particularly favorable. The preference of thrombin for distinctly substituted piperidine derivatives and its generally higher (compared with trypsin) affinity for benzamidine and arginine-based inhibitors can be accounted for by these thrombin inhibitor models. PMID- 2226436 TI - Casein kinase II phosphorylates DNA-polymerase-alpha--DNA-primase without affecting its basic enzymic properties. AB - Immunoaffinity-purified DNA-polymerase-alpha--DNA-primase complex from calf thymus was phosphorylated in vitro by highly purified casein kinase II from the same tissue. Specific phosphorylation of the DNA-polymerizing alpha subunit and the primase-associated gamma subunit was observed. About 1 mol phosphate/mol polymerase--primase was incorporated. Despite this effect, neither the DNA polymerase nor the DNA primase activity were changed after phosphorylation by casein kinase II. Furthermore, dephosphorylation of polymerase--primase with alkaline phosphatase did not change the polymerase or the primase activity to a significant extent. Moreover, both alkaline phosphatase and casein kinase II had no effect on the processivity of DNA synthesis and on the lengths and amounts of primers formed by the DNA primase. Because DNA polymerase alpha maintained all its basic properties even after extensive treatment with alkaline phosphatase, it is unlikely that phosphorylation has a direct influence on the activities of the DNA-polymerase-alpha--DNA-primase complex. The possible influence of post translational phosphorylation on the formation of a complex of polymerase alpha and its accessory proteins is discussed. PMID- 2226437 TI - Coamplification of mu class glutathione S-transferase genes and an adenylate deaminase gene in coformycin-resistant Chinese hamster fibroblasts. AB - In Chinese hamster fibroblasts, we previously detected an expressed gene located near the AMP deaminase gene. This gene was named Y1. Upon selection for resistance to coformycin, an inhibitor of AMP deaminase activity, both genes were amplified in several mutants. We have determined the complete nucleotide sequence of Y1 cDNA and identified the Y1 gene as a mu class glutathione S-transferase gene by comparison with sequences present in a data bank. Accordingly, Y1 amplified mutants express an increased glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene; this activity, as well as the abundance of the corresponding RNA, appears, however, to reach a limit despite further increase in the Y1 gene copy number during successive amplification steps. Southern blot experiments showed that Y1 belongs to a multigene family, all or part of which has been amplified in mutant lines. These data provide a method to amplify and to overexpress the mu class of the glutathione S-transferase gene family on the basis of its linkage with the AMP deaminase gene. PMID- 2226438 TI - Two glyceraldehyde-3-phosphate dehydrogenase isozymes from the koningic acid (heptelidic acid) producer Trichoderma koningii. AB - The sesquiterpene lactone koningic acid (heptelidic acid) irreversibly inactivated glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde 3 phosphate: NAD+ oxidoreductase (phosphorylating)] (EC 1.2.1.12) (GAPDH) and thus inhibits glycolysis. The koningic-acid-producing strain of Trichoderma koningii M3947 was shown to contain the koningic-acid-resistant GAPDH isozyme (GAPDH I) under conditions of koningic acid production. In peptone-rich medium, however, no koningic acid production was observed, and the koningic-acid-sensitive GAPDH isozyme (GAPDH II), in addition to the resistant enzyme, was produced. Both enzymes were tetramer with a molecular mass of 152 kDa (4 x 38 kDa) and lost enzyme activity when two of the four cysteine residues reacted with koningic acid. The apparent Km values of GAPDH I and II for glyceraldehyde 3-phosphate were 0.54 mM and 0.33 mM, respectively. The former isozyme was inhibited 50% by 1 mM koningic acid but not affected at 0.1 mM, while the latter isozyme was inhibited 50% at 0.01 mM. The immunochemical properties and partial amino acid sequences suggested that the two isozymes have different molecular structures. These results suggest that GAPDH I is responsible for the glycolysis in T. koningii when koningic acid is produced. PMID- 2226439 TI - Purification and characterization of a cysteine proteinase from silkworm eggs. AB - Eggs of the silkworm, Bombyx mori, contain a high level of a proteinase which is most active in acidic pH region. The proteinase was purified from an extract of eggs by a six-step procedure which included conventional chromatographic fractionations. The molecular mass of the proteinase was estimated to be 350 kDa by gel filtration and 47 kDa by electrophoresis on sodium dodecyl sulfate/polyacrylamide gels, suggesting an octameric structure. The amino acid composition was found to resemble that of mammalian lysosomal cysteine proteinases, in particular cathepsin L. The NH2-terminal 10-residue sequence is Val-Gln-Phe-Phe-Asp-Leu-Val-Lys-Glu-Glu-. The enzyme appears to be a member of the class of cysteine proteinases since it was strongly inhibited by sulfhydryl reactive compounds and N-[N-(1,3-trans-carboxyoxiran-2-carbonyl)-L-leucyl] agmatine (E-64). The enzyme hydrolyzed various protein substrates, such as hemoglobin, vitellogenin, vitellin, and lipophorin, with maximal activity around pH 3-3.5. The specificity of the cleavage sites in the oxidized B chain of insulin was rather well defined and there was high affinity for hydrophobic residues at the P2 and P3 positions. The cysteine proteinase is thought to be involved in protein degradation during embryonic development of silkworm eggs. PMID- 2226440 TI - Cooperative homotropic interaction of L-noradrenaline with the catalytic site of phenylalanine 4-monooxygenase. AB - Catecholamines (adrenaline, noradrenaline and dopamine) are potent inhibitors of phenylalanine 4-monooxygenase (phenylalanine hydroxylase, EC 1.14.16.1). The amines bind to the enzyme by a direct coordination to the high-spin (S = 5/2) Fe(III) at the active site (charge transfer interaction), as seen by resonance Raman and EPR spectroscopy. Experimental evidence is presented that a group with an apparent pKa value of about 5.1 (20 degrees C) is involved in the interaction between the catecholamine and the enzyme. The high-affinity binding of L noradrenaline to phenylalanine hydroxylase, as studied by equilibrium microdialysis (anaerobically) and ultrafiltration (aerobically), shows positive cooperativity (h = 1.9); at pH 7.2 and 20 degrees C the rat enzyme binds about 0.5 mol L-noradrenaline/mol subunit with a half-maximal binding (S50) at 0.25 microM L-noradrenaline. No binding to the ferrous form of the enzyme was observed. The affinity decreases with decreasing pH, by phosphorylation and by preincubation of the enzyme with the substrate L-phenylalanine, while it increases after alkylation of the enzyme with the activator N-ethylmaleimide. Preincubation of the enzyme with L-phenylalanine also leads to a complete loss of the cooperativity of L-noradrenaline binding (h = 1.0). The many similarities in binding properties of the inhibitor L-noradrenaline and the activator/substrate L phenylalanine makes it likely that the cooperative interactions of these effectors are due to their binding to the same site. The high-affinity of catecholamines to phenylalanine hydroxylase is a valuable probe to study the active site of this enzyme and is also relevant for the homologous enzyme tyrosine hydroxylase, which is purified as a stable catecholamine-Fe(III) complex. PMID- 2226441 TI - Ornithine/phosphate antiport in rat kidney mitochondria. Some characteristics of the process. AB - [14C]Ornithine uptake by rat kidney mitochondria has been investigated according to the stop inhibitor method by using praseodimium chloride as an inhibitor. The existence of an ornithine/Pi exchange was found occurring with 1:1 stoichiometry. Both uptake and efflux follow first-order kinetics with a k of 2.4 min-1. Uptake increases with increasing pH. The activation energy for the process is 58.6 kJ/mol and Q10 is 2.6. Ornithine/Pi exchange is electrical and energy-dependent, as suggested by the sensitivity of the process to the ionophores valinomycin and nigericin. Measurements both of proton movement across the mitochondrial membrane and of membrane potential strongly suggest that ornithine uptake into mitochondria is driven by the electrochemical proton gradient via the dependent ornithine/Pi translocator and delta pH-dependent Pi carrier. PMID- 2226443 TI - Two of the three genetic variants of goat alpha s1-casein which are synthesized at a reduced level have an internal deletion possibly due to altered RNA splicing. AB - This paper describes the elucidation of the primary structure of the three genetic variants of goat alpha s1-casein, alpha s1-Cn D, E and F, which have been found to be associated with reduced amounts of alpha s1-casein in milk. Variant E has the same electrophoretic mobility as variant B, but differs from the latter by the substitutions of Arg for Lys and of Thr for Ala at positions 100 and 195. A genetically controlled event which does not affect the amino acid sequence of this variant might be responsible for its lower rate of synthesis compared to that of alpha s1-casein B. The deletion of 11 amino acids at positions 59-69 and of 37 amino acids at positions 59-95 in variant B leads to variants D and F. In both cases the deletions, which start at the same position of the polypeptide chain, include the major phosphorylation site of the protein. On the basis of sequence data for casein genes and cDNAs, it was concluded that the deletions occurring in the D and F variants are due to the exclusion of one and several exons, respectively. The observed deletions in the proteins could thus be the consequence of splice site mutations which would induce altered RNA processing and hence reduce the rate of synthesis of the casein. PMID- 2226442 TI - Developmental regulation of metallothionein mRNA, zinc and copper levels in rainbow trout, Salmo gairdneri. AB - The metallothionein (MT) gene expression profile was followed in rainbow trout during early embryo development and in liver and gonads during the period of sexual maturation. The hepatic MT mRNA levels increase at the end of sexual maturation in both male and female rainbow trout. Although both isoforms of MT mRNA accumulate in the liver, there is a preferential increase in MT-A in the female liver. Concomitantly with this increase in MT there is a redistribution of zinc and copper to MT. In the juvenile female there is an abundance of MT mRNA in the ovaries. This is correlated to high levels of zinc in the MT fraction upon Sephadex G-75 chromatography. During ovary development the MT mRNA levels and the MT-bound zinc levels drop, with an increase in zinc being bound to high-molecular mass proteins. At ovulation most of the zinc is found in the membrane portion upon centrifugation. In contrast to the ovaries, there are no apparent changes in either trace metal distribution or MT mRNA levels during testis development. In the developing embryo there is an increase in MT-bound copper at gastrulation. This is accompanied by an increase in both isoforms of MT mRNA. At hatch both the copper and zinc levels increase in the MT fraction, with a concomitant increase in mainly MT-A mRNA. These findings indicate that the variations in MT mRNA levels during development are closely associated with metal regulation. PMID- 2226444 TI - Lipases catalyse hydrolysis of fatty acid anhydrides. AB - Regio-specific and non-regio-specific lipases from mammals and microorganisms catalyse the hydrolysis of short, medium and long-chain fatty acid anhydrides. All the lipases tested in the present study can catalyse the hydrolysis of pure fatty acid anhydrides more efficiently than that of glycerol tributyrate. Molecular turnovers more than four times higher than that measured using glycerol tributyrate were calculated. The presence of 0.5% (by mass) anhydride in a triacylglyceride can double the initial rate of proton release during enzymatic hydrolysis. This should be taken into account when testing the chain specificity of a lipase for various synthetic substrates. Lipase inhibition was found to be associated very often with anhydride hydrolysis. The inhibition rates depended on the anhydride and the origin of the lipase. Inhibition of lipase activity is probably due to the formation of a poorly reversible acyl-lipase complex which differs from the classical fully reversible acyl-lipase complex at the catalytic centre. PMID- 2226445 TI - In vivo 13C-NMR studies on the metabolism of the lugworm Arenicola marina. AB - 13C-NMR natural-abundance spectra of specimens of Arenicola marina obtained, showed seasonal changes in the concentration of some metabolites, with the osmolite alanine as well as triacylglyceride storage compounds present at high concentrations. Glycogen was sometimes only barely detectable due to the low natural abundance level of 13C. Glycogenic metabolism of the lugworm A. marina was studied in vivo by 13C-NMR spectroscopy using 13C-labelled glucose. During recovery from a hypoxic period [1-13C]glucose was incorporated into glycogen. [1 13C]Glucose was injected 5 h after the end of hypoxia to guarantee sufficient and reliable 13C labelling of glycogen. An earlier injection of [1-13C]glucose led to considerably diminished incorporation of 13C-labelled glucosyl units into glycogen, probably due to the consumption of the available glucose as fuel for ATP production. No scrambling of 13C into the C6 position of glycogen was observed, indicating a lack of gluconeogenic activity. 13C was also incorporated into the C3 positions of alanine and alanopine. To assign correctly this last 13C NMR resonance, the compound was synthesized biochemically. No labelling of glycogen was observed when [3-13C]alanine was injected into the coelomic cavity with similar incubation conditions being used. The 13C of [1-13C]glucose, incorporated into glycogen, showed a very low turnover rate in normoxic lugworms as shown by two 13C(1H)-NMR spectra, one obtained 48 h after the other. On the other hand, in hypoxia lugworms the signal due to 13C-labelled glycogen decreased very rapidly proving a high turnover rate. The disappearance of 13C from glycogen during the first 24 h of hypoxia indicates that the last glycosyl units to be synthesized are the first to be utilized. Lugworms were quite sensitive to the 1H decoupling field used for obtaining the 13C(1H)-NMR spectra, especially at 11.7 T. Using bi-level composite-pulse decoupling and long relaxation delays, no tissue damage or stress-dependent phosphagen mobilization, as judged by 31P-NMR spectroscopy, was observed. PMID- 2226447 TI - Amino acid sequence and disulfide bridges of an antifungal protein isolated from Aspergillus giganteus. AB - A very basic secreted protein which displays antifungal activity was isolated from the medium of the mold Aspergillus giganteus. The protein consists of 51 amino acid residues whose sequence was determined as Ala-Thr-Tyr-Asn-Gly-Lys-Cys Tyr-Lys-Lys-Asp-Asn- Ile-Cys-Lys-Tyr-Lys-Ala-Gln-Ser-Gly-Lys-Thr-Ala-Ile-Cys-Lys Cys-Tyr-Val- Lys- Lys-Cys-Pro-Arg-Asp-Gly-Ala-Lys-Cys-Glu-Phe-Asp-Ser-Tyr-Lys-Gly Lys-Cys- Tyr-Cys . Disulfide bonds were formed between Cys7-Cys33, Cys14-Cys40, Cys26-Cys28 and Cys49-Cys51. These results suggest that the antifungal protein forms a loop structure and is similar to phospholipase A2. PMID- 2226446 TI - A 31P-NMR study of bovine adrenocortical mitochondrial metabolic activities. AB - High-field 31P-NMR spectroscopy has been used to study the metabolic activities of coupled bovine adrenocortical mitochondria in vitro. These differentiated organelles use oxygen as a substrate to support both oxidative phosphorylation and specific steroid hydroxylation reactions. The NMR technique allowed the resolution of two inorganic phosphate signals, attributed to the matrix and external medium phosphate pools, at low and high field, respectively. These signals were used to calculate the respective Pi concentrations and to obtain the pH of the two corresponding compartments. In addition, the NMR spectra displayed resonance signals corresponding to ADP added to the medium and to ATP synthesized during oxidative phosphorylation. NMR analysis of the mitochondrial perchloric acid extracts identified the major phosphate-containing metabolites, namely NADP+, NAD+, phosphocholine, phosphoethanolamine, sn-glycero-(3)phosphocholine, AMP, ADP, ATP and Pi. Upon addition of ADP and malate to the oxygenated suspension, the kinetics of mitochondrial external Pi consumption and of ATP synthesis, along with the intra- and extraorganelle pH variations could be monitored over time periods of approximately 30 min, in the absence and presence of different steroid hydroxylation substrates. A major observation was that oxidative phosphorylation, which takes place in the absence of steroid, was markedly inhibited as soon as steroid hydroxylation was operating. These observations show the potential of 31P-NMR spectroscopy in the study of metabolic activities of isolated intact mitochondrial organelles. Such an approach appears promising for further determination of the underlying mechanisms in the balance between vital oxidative phosphorylation and differentiated steroid hydroxylation which are under hormonal control in adrenocortical mitochondria as well as in other steroidogenic cell systems. PMID- 2226448 TI - Protozoan myoglobin from Paramecium caudatum. Its autoxidation reaction and hemichrome formation. AB - Native oxymyoglobin (MbO2) was isolated directly from the cells of Paramecium caudatum with complete separation from metmyoglobin (metMb) on a DEAE-cellulose column. It was examined for its spectral and stability properties. When compared with sperm whale MbO2 used as a reference, Paramecium MbO2 was found to be much more susceptible to autoxidation over a wide range of pH (4-11) in 0.1 M buffer at 25 degrees C. Kinetic analysis has revealed that a proton-catalyzed displacement of O2- from MbO2 by an entering water molecule can play a dominant role in the autoxidation reaction of Paramecium MbO2 to metMb, as in the case of sperm whale MbO2 involving the distal histidine as its catalytic residue. At pH values higher than 9.5, however, Paramecium MbO2 was found to be oxidized to yield a hemichrome. The spontaneous formation of hemichromes is at variance with the other known myoglobins and is therefore discussed in relation to the unusual amino acid sequence of Paramecium myoglobin having a large number of deletion. PMID- 2226449 TI - Carbonyl reductases from rat testis and vas deferens. Purification, properties and localization. AB - Three enzyme forms (T1, T2, T3) from rat testis and two from rat vas deferens (V1, V2) of carbonyl reductase have been highly purified to apparent homogeneity. These carbonyl reductases from rat reproductive organs have several similarities in terms of molecular mass (32-33 kDa), isoelectric point (pI 5.9-6.4), immunochemical properties, cofactor requirement (NADPH dependency) and sensitivity to sulfhydryl reagents. The isoenzymes from the vas deferens (V1, V2) have similar catalytic activities, whereas those from the testis (T1, T2, T3) showed different catalytic activities from each other. All enzymes, however, reduced quinones, aromatic aldehydes and ketones, while T3, V1 and V2 were characterized as possessing high affinity towards prostaglandins. An immunoinhibition study using a specific antibody indicated that these enzymes were solely responsible for the overall catalytic activities of 13, 14-dihydro-15 oxo-prostaglandin F2 alpha, 4-benzoylpyridine, and 4-nitroacetophenone reduction and prostaglandin F2 alpha oxidation in both testis and vas deferens cytosol. The immunohistochemical staining revealed a positive immunoreactivity to antibody only in the Leydig cells of the testis, but neither the germ cells nor Sertoli cells in the seminiferous tubule. The staining also showed that the enzymes in the vas deferens were primarily localized in mucosal epithelium cells. PMID- 2226450 TI - Kinetic analysis of the human erythrocyte glyoxalase system using 1H NMR and a computer model. AB - 1H NMR was used with methylglyoxal, purified by an HPLC technique, to study the kinetics of the human erythrocyte glyoxalase system. 1H NMR enabled the direct measurement of the time-dependent changes in concentrations of the two hydrates of methylglyoxal, which have not previously been directly measurable, as well as measurement of substrates and products of the glyoxalase enzyme system in the human red blood cell. A computer model of the reaction scheme was developed and NMR data numerically analyzed, thus allowing a complete kinetic description of the reactions. The rate constants describing the chemical equilibria between the hydrated species of methylglyoxal were determined by this numerical analysis or by a saturation-transfer technique, and found to be much slower (by several orders of magnitude) than previously determined by other methods. The kinetic parameters describing the enzyme-catalyzed reactions were also determined from experiments using a dilute haemolysate that was added to solutions of methylglyoxal and reduced glutathione (GSH). The maximal velocity of glyoxalase 1 is threefold greater (Vmax = 70.4 +/- 4.7 mmol.min-1.1 packed cells-1) than glyoxalase 2(Vmax = 24 +/- 5 mmol.min-1.1 packed cells-1) and it exhibits threefold-greater affinity for its substrate (Km = 0.46 +/- 0.04 mM) than the second enzyme (Km = 1.5 +/- 0.4 mM). Both enzymes are subject to competitive inhibition; glyoxalase 1 by reduced glutathione (KiGSH = 7.88 +/- 0.16 mM) and glyoxalase 2 by the hemithioacetal (HTA) of methylglyoxal and GSH (KiHTA = 0.29 +/- 0.04 mM). PMID- 2226451 TI - Subcellular localisation of dihydrolipoamide dehydrogenase and detection of lipoic acid in bloodstream forms of Trypanosoma brucei. AB - In the long-slender bloodstream form of Trypanosoma brucei, the enzyme dihydrolipoamide dehydrogenase exists in the absence of the 2-oxo-acid dehydrogenase complexes of which it is normally a component, and appears to be associated with the plasma membrane of the organism [Danson, M. J., Conroy, K., McQuattie, A. & Stevenson, K. J. (1987) Biochem. J. 243, 661-665]. In the present paper, a complete subcellular fractionation of T. brucei has been carried out and, by comparison with marker enzymes, it is confirmed that the dihydrolipoamide dehydrogenase is indeed associated with the plasma membrane. In addition, we now provide evidence that the distribution of the enzyme is over the whole surface of the membrane, including the flagellar pocket region, and that the enzyme is not found in any other cellular fraction. A study of the latency of the enzyme suggests that it is located on the cytoplasmic surface of the plasma membrane. The discovery of the presumed substrate of dihydrolipoamide dehydrogenase, lipoic acid, is reported for T. brucei. Using a biological assay involving a strain of Escherichia coli that requires lipoic acid for growth, we have found that acid hydrolysed extracts of T. brucei contain 1.7 (+/- 0.2) ng of the cofactor/mg protein. The chemical nature of the lipoic acid was confirmed by gas chromatography/mass spectrometry. PMID- 2226453 TI - Comparison of three classes of human liver alcohol dehydrogenase. Emphasis on different substrate binding pockets. AB - Conformational models of the three characterized classes of mammalian liver alcohol dehydrogenase were constructed using computer graphics based on the known three-dimensional structure of the E subunit of the horse enzyme (class I) and the primary structures of the three human enzyme classes. This correlates the substrate-binding pockets of the class I subunits (alpha, beta and gamma in the human enzyme) with those of the class II and III subunits (pi and chi, respectively) for three enzymes that differ in substrate specificity, inhibition pattern and many other properties. The substrate-binding sites exhibit pronounced differences in both shape and properties. Comparing human class I subunits with those of class II and III subunits there are no less than 8 and 10 replacements, respectively, out of 11 residues in the substrate pocket, while in the human class I isozyme variants, only 1-3 of these 11 positions differ. A single residue, Val294, is conserved throughout. The liver alcohol dehydrogenases, with different substrate-specificity pockets, resemble the patterns of other enzyme families such as the pancreatic serine proteases. The inner part of the substrate cleft in the class II and III enzymes is smaller than in the horse class I enzyme, because both Ser48 and Phe93 are replaced by larger residues, Thr and Tyr, respectively. In class II, the residues in the substrate pocket are larger in about half of the positions. It is rich in aromatic residues, four Phe and one Tyr, making the substrate site distinctly smaller than in the class I subunits. In class III, the inner part of the substrate cleft is narrow but the outer part considerably wider and more polar than in the class I and II enzymes. In addition, Ser (or Thr) and Tyr in class II and III instead of His51 may influence proton abstraction/donation at the active site. PMID- 2226452 TI - The three cysteine residues of cytoplasmic aspartyl-tRNA synthetase from Saccharomyces cerevisiae are not essential for its activity. AB - Cytoplasmic aspartyl-tRNA synthetase from Saccharomyces cerevisiae is a dimer made up of identical subunits (Mr 63,000) each of these containing three cysteines (residues 255, 512 and 519 in the amino acid sequence). Thiol-specific probes were used to label these cysteines and study the resulting effect of the modification on the kinetic parameters of both the ATP/PPi exchange and tRNA aminoacylation reactions. Using the classical techniques of protein chemistry it was shown that none of the three cysteines was labelled with iodoacetic acid, whilst N-ethylmaleimide and 5,5'-dithiobis(2-nitrobenzoate) reacted with Cys512 and Cys255, respectively. Only the latter modification was accompanied by a decrease in the rates of both enzyme activities whilst the Km values for the various substrates remained unaffected. Site-directed mutagenesis was also used to replace each of the three cysteines by other residues, either individually or simultaneously. For these experiments the enzyme was expressed in Escherichia coli using an expression vector bearing the structural gene in which the first 13 codons were replaced by the first 14 of the CII lambda gene. The resulting substitution in the amino-terminal part of the expressed enzyme had no effect on the kinetic parameters, compared to those of the enzyme purified from S. cerevisiae. Taking into account the consequences of such substitutions, as well as those of chemical modifications on the two reactions catalysed by the enzyme. ATP/PPi exchange and tRNA aminoacylation, it could be concluded that none of these three cysteines plays any essential role in either substrate binding or catalysis. PMID- 2226454 TI - The tissue-specific expression of the thyroglobulin gene requires interaction between thyroid-specific and ubiquitous factors. AB - Thyroid-specific expression of the rat thyroglobulin gene is mediated by transcriptional control. Sufficient DNA sequence information to confer thyroid specific expression to a heterologous gene is contained between positions -168 and +39. DNA-binding studies have demonstrated that this region interacts with two thyroid-specific factors (TTF-1 and TTF-2), and a ubiquitous factor (UFA). Here we have characterized three elements within the promoter, A, K, and C, which are important for promoter activity in thyroid cells. We have shown by mutational analysis that the interaction of TTF-1 with the A and C regions. UFA with the A region, and TTF-2 with the K region are required for full promoter activity. The complex interactions in the A region can be replaced by the substitution of the UFA/TTF-1-binding site with a high-affinity TTF-1 binding site. There is a correlation between the presence of TTF-1 and TTF-2 DNA-binding activities and the expression of thyroglobulin, which implies that the mechanism restricting thyroglobulin expression to thyroid cells is mediated through the control of the expression, or the activity, of TTF-1 and TTF-2. PMID- 2226455 TI - Export and purification of a cytoplasmic dimeric protein by fusion to the maltose binding protein of Escherichia coli. AB - A hybrid between the maltose-binding protein (MalE) of Escherichia coli and the gene 5 protein (G5P) of phage M13 was constructed at the genetic level. MalE is a monomeric and periplasmic protein while G5P is dimeric and cytoplasmic. The hybrid (MalE-G5P) was synthesized in large amounts from a multicopy plasmid and efficiently exported into the periplasmic space of E. coli. The export was dependent on the integrity of the signal peptide. MalE-G5P was purified from a periplasmic extract by affinity chromatography on cross-linked amylose, with a yield larger than 50,000 molecules/E. coli cell. The hybrid specifically bound denatured but not double-stranded DNA cellulose, as native G5P. Sedimentation velocity and gel-filtration experiments showed that MalE-G5P exists as a dimer. Thus, it was possible to efficiently translocate through the membrane a normally cytoplasmic and dimeric protein, by fusion to MalE. Moreover, the passenger protein kept its activity, specificity and quaternary structure in the purified hybrid. MalE-G5P will enable the study of mutant G5P that no longer binds single stranded DNA and therefore cannot be purified by DNA-cellulose chromatography. PMID- 2226456 TI - Bovine hemoglobin pseudo-crosslinked with mono(3,5-dibromosalicyl)-fumarate. AB - Under oxygenated conditions bovine hemoglobin reacts with mono(3,5 dibromosalicyl)-fumarate which specifically acylates the EF5 lysines in the beta cleft of the protein. The chemical modification introduces in the molecule a pseudo-crosslink which hinders the dissociation of the hemoglobin molecule into dimers. Retention time in circulation of the chemically modified bovine hemoglobin, measured in the rat, is increased fivefold with respect to untreated bovine hemoglobin. The oxygen affinity at 37 degrees C and at pH 7.4, has a P50 = 5.4 kPa and a value of n = 1.9. Under the same experimental conditions the oxygen affinity is not sensitive to anions and polyanions whereas it is sensitive to CO2. The Bohr effect is shifted toward the alkaline pH range by 0.5-1: the maximum number of protons released is 1.5/tetramer, similar to normal bovine hemoglobin (1.8 protons/tetramer). Analysis of the binding isotherms, using the two-state Monod-Wyman-Changeux model and fixing the value of the allosteric constant L = 10(5), shows that the oxygen affinity of the T structure is not modified, and that the low oxygen affinity of the system is due to a decrease of the oxygen affinity of the R structure. Analysis using the sequential Adair model shows a modification of the overall binding constants and suggests a redistribution of the intermediate species of oxygenation. PMID- 2226458 TI - Distribution of the early light-inducible protein in the thylakoids of developing pea chloroplasts. AB - The distribution of the early light-inducible protein (ELIP) of pea (Pisum sativum) between grana and stroma thylakoids was studied. An antibody raised against a bacterial-expressed fusion protein containing ELIP sequences was used. Illumination of dark-grown pea seedlings causes an accumulation of the ELIP in the thylakoid membranes with a maximum level at 16 h. During continuous illumination exceeding 16 h the level decreases again. The fractionation of thylakoid membranes of 48-h-illuminated pea seedlings in grana and stroma thylakoids reveals that there is no uniform distribution of ELIP in the thylakoids. Rather 60-70% of ELIP was found in the stroma thylakoids and 30-40% in the grana thylakoids. This distribution is in accordance with that of photosystem I but not with that of photosystem II. After Triton-X-100 solubilization almost all ELIP is found in the photosystem-I-containing fraction. This also supports an association of ELIP with photosystem I. PMID- 2226457 TI - Physicochemical studies of human O6-methylguanine-DNA methyltransferase. AB - O6-Methylguanine-DNA methyltransferase, present in most organisms, removes mutagenic and carcinogenic O6-alkylguanine from DNA by accepting the alkyl group in a stoichiometric reaction. The protein has been partially purified from human placenta. It reacts with second-order rate constants of 2.20 x 10(8) and 0.067 x 10(8) lmol-1 min-1 at 37 degrees C for duplex and single-stranded DNA substrates, respectively. The corresponding value for the alkylated base in synthetic poly(dC, dG, m6dG) is 0.02 x 10(8) l mol-1 min-1. The native protein is monomeric with a molecular mass of 22-24 kDa. Methylation of the protein does not lead to a gross change in its conformation but causes a slight reduction in its isoelectric point of 6.2. Although DNA protects the protein from heat inactivation, both duplex and single-stranded DNAs inhibit its activity in a concentration-dependent manner. The transferase reaction rate is also strongly inhibited by salt with about 20% of the maximum rate observed in physiological ionic strength. This inhibition is nonspecific with respect to the ions of univalent salts. PMID- 2226459 TI - Effect of the tyrosine 96 hydrogen bond on the inactivation of cytochrome P 450cam induced by hydrostatic pressure. AB - The effects of removal of the tyrosine 96 hydrogen bond on the stability and conformational events of cytochrome P-450cam are presented in this communication. Hydrostatic pressure has been used as a tool to perturbe the structure leading to the formation of cytochrome P-420, an inactivated but soluble and undenatured form of the enzyme. We show that the spin transition of cytochrome P-450cam, which is known to be influenced by hydrostatic pressure, is affected by this single mutation. The free energy of stabilisation of native substrate-free cytochrome P-450cam is not affected by the removal of the tyrosine 96 hydrogen bond via mutagenesis to phenylalanine, whereas the substrate-bound protein shows a difference of 21 kJ/mol. These results, as well as an observed 110 ml/mol difference for the volume of the inactivation reaction between substrate-bound native and mutant proteins, have been interpreted in terms of a more hydrated heme pocket for the site-directed mutant at position 96 compared to the wild-type protein where camphor is tightly bound via the tyrosine 96 hydrogen bond and water excluded from the active site. PMID- 2226460 TI - Dual effects of the ricin A chain on protein synthesis in rabbit reticulocyte lysate. Inhibition of initiation and translocation. AB - Ricin A chain caused inhibition of protein synthesis by reticulocyte lysate with concomitant depurination of 28S rRNA. The partial reaction(s) of protein synthesis inhibited was investigated by following the appearance of [35S]methionine from initiator [35S]Met-tRNA into 40S ribosomal subunits, 80S monosomes and polysomes. Ricin A chain caused an accumulation of [35S]Met in monosomes which did not enter polysomes. In these respects the effects of the ricin A chain resembled those of diphtheria toxin, an inhibitor of elongation factor-2-catalyzed translocation. This is consistent with the previously proposed site of action of ricin as an inhibitor of elongation. However, the inhibitory effects of the ricin A chain and diphtheria toxin are not equivalent because we observed that the rate of formation of the 80S initiation complex was reduced approximately sixfold with the ricin A chain relative to diphtheria toxin. Analysis of methionine-containing peptides bound to 80S monosomes in ricin-A chain-inhibited and diphtheria-toxin-inhibited lysates, programmed with globin mRNA, revealed a predominance of Met-Val, suggesting that the elongation cycle is inhibited at the translocation step. Translocation was also implicated as the step blocked in both the ricin-A-chain-inhibited and diphtheria-toxin-inhibited lysates, by the finding that nascent peptide chains were unreactive towards puromycin. It is concluded that ricin-A-chain-modified ribosomes are deficient in two protein synthesis partial reactions: the formation of the 80S initiation complex during initiation and the translocation step of the elongation cycle. PMID- 2226461 TI - Secondary structure and dosage of soluble and membrane proteins by attenuated total reflection Fourier-transform infrared spectroscopy on hydrated films. AB - Attenuated total reflection Fourier-transform infrared spectroscopy of thin hydrated films of soluble and membrane protein included in a phospholipid bilayer is shown to provide useful information as to the secondary structure of the protein. The analysis of the amide I band of deuterated samples by Fourier self deconvolution followed by a curve fitting was performed by a new procedure in which all the input parameters are generated by the computer rather than by the investigator. The results of this analysis provide a correct estimation of the alpha-helix and beta-sheet structure content with a standard deviation of 8.6% when X-ray structures are taken as a reference. We also show that the orientation of the different secondary structures resolved by the Fourier self deconvolution/curve-fitting procedure and of the phospholipid acyl chains can be simultaneously evaluated for membrane proteins reconstituted in a lipid bilayer. Of special interest for reconstitution of membrane proteins, the lipid/protein ratio can be accurately and quickly determined from the infrared spectrum. PMID- 2226462 TI - myo-inositol oxygenase from rat kidneys. Substrate-dependent oligomerization. AB - myo-Inositol from rat kidneys, an oligomeric protein with apparent molecular mass of about 270 kDa can be dissociated under mild conditions to structured 16.8-kDa monomers. This dissociation can be reversed at high protein concentrations at room temperature. The corresponding apparent dimerization constant K2app = 1.38 x 10(5) M-1, the corresponding rate constant k2 = 350 s-1.M-1, and the apparent constant for the association of dimers, K4app = 2.7 x 10(6) M-1. Reassociation is significantly enhanced in the presence of the substrate and iron(II) (K2app = 9.8 x 10(5) M-1; K4app = 3.75 x 10(6) M-1, k2 = 1750 s-1.M-1, at 20 mM myo-inositol and 0.5 mM FeSO4). Under these conditions almost 100% of the original enzymatic activity was reconstituted. Monomers, with or without bound ligands, lack catalytic activity, whereas the dimer is likely to be the elementary active enzyme-building unit. The effects of myo-inositol on the dimerization lead to the conclusion that this step is both mediated and facilitated by the substrate. PMID- 2226463 TI - A novel testis-specific 105-kDa protein related to the 90-kDa heat-shock protein. AB - Brain 90- and 100-kDa heat-shock proteins (HSP90 and HSP100) were purified and antibodies against them prepared. The two antibodies were very specific and did not cross-react with each other. In rat, immunoblotting with the anti-HSP90 antibody showed the most abundant presence of HSP90 in testis as well as brain, compared with lung, liver, spleen, kidney, cardiac muscle, ovarium and uterus. The anti-HSP90 antibody showed the presence of a new 105-kDa protein in rat testis. This novel 105-kDa protein was also detected in brain at a very low concentration but not in HeLa cells or other organs including the uterus and ovarium. The testis 105-kDa protein was purified from rat testis; although it was clearly separable from HSP90 by two-dimensional gel electrophoresis, Q-Sepharose and hydroxyapatite column chromatographies, the properties of this protein were very similar to HSP90. The similarity was higher than 60% on peptide mapping with trypsin digestion, the 105-kDa protein cross-reacted with anti-HSP90 antibody, both were bound similarly to heparin-Sepharose gel and both are located in the cytosol fraction. When the 105-kDa protein was fractionated by HPLC, a molecular mass of 195 kDa was calculated, indicating that it is composed of two identical subunits, similarly to HSP90. The 105-kDa protein did not react with the anti HSP100 antibody. There was a slight similarity between the 105-kDa protein and HSP100 on the peptide mapping. HSP100 was present in the microsomal fraction as well as in the cytosol. It is concluded that the 105-kDa protein is a testis specific and HSP90-related protein. PMID- 2226464 TI - Analysis of the binding of glyceraldehyde-3-phosphate dehydrogenase to microtubules, the mechanism of bundle formation and the linkage effect. AB - The binding of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to microtubules was analysed by the determination of the concentration of the free enzyme in equilibrium with the complex. At low ionic strength (0.03 M) the binding data are best described by a sum of high (Kd = 0.28 microM) and low affinity (Kd = 7.14 microM) sites, showing positive cooperativity. Addition of 1 mM adenosine 5' [beta,gamma-imido]triphosphate (p[NH]ppA) or increasing the ionic strength to 0.1 M reduces the binding constant of the high-affinity sites considerably. Adding microtubule-associated proteins (at I = 0.1 M) does not appreciably influence the affinities. Total stoichiometries vary over 2.1-1.2 tubulin dimers involved in a binding site for GAPDH. Bundling is reduced concomitantly with the reduction of the affinities and the increase of the stoichiometry to close to 1 mol GAPDH/mol tubulin dimer. The critical concentration of tubulin is practically not influenced by the binding of the enzyme. This behaviour is discussed in terms of the concept of linked functions. p[NH]ppA dissociates the bundles very rapidly. Analytical sedimentation studies showed that the dissociation of the bundles by p[NH]ppA is not due to the dissociation of the tetrameric enzyme. Bundling slows down association and dissociation of microtubules. The rate of bundle formation, after addition of GAPDH to preformed microtubules, is not dependent on the GAPDH concentration. PMID- 2226465 TI - Binding of a photoaffinity analogue of pyridoxal to pyridoxal kinase. AB - The binding of pyridoxal analogues to the structural domains of pyridoxal kinase was studied by fluorescence spectroscopy and chromatographic techniques. Two fragments of 24 and 16 kDa, arising from limited proteolysis of the native enzyme, were separated by ion-exchange chromatography and used for binding studies with pyridoxal oxime. Fluorometric titrations yielded dissociation constants of 6 and 12.4 MicroM for pyridoxal oxime bound to the native enzyme and 24-kDa fragment, respectively. 4-(4-Azido-2-nitrophenyl)-pyridoxamine, a new photolabeling reagent, binds irreversibly to the kinase with concomitant loss of catalytic activity. The modified kinase (2.1 mol label/mol dimer) yields two fragments upon limited proteolysis with chymotrypsin. The two fragments were separated by reverse-phase HPLC and SDS/polyacrylamide gel electrophoresis. Radiolabeled ligand was detected only in the 24-kDa fragment. It is postulated that the pyridoxal binding site is located in the 24-kDa structural domain. PMID- 2226466 TI - Inhibition of factor X and factor V activation by dermatan sulfate and a pentasaccharide with high affinity for antithrombin III in human plasma. AB - There is evidence that by catalyzing thrombin inhibition, several glycosaminoglycans can inhibit the thrombin-mediated amplification reactions of coagulation and thereby delay prothrombin activation. The two amplification reactions can apparently be catalysed by endogenously generated factor Xa and thrombin. This study provides evidence which suggests that on a molar basis, an agent which can only catalyse thrombin inhibition is approximately 10 times more effective than an agent which can only catalyse factor Xa inhibition in their ability to inhibit intrinsic prothrombin activation. We determined the concentrations of each of heparin, dermatan sulfate and a pentasaccharide with high affinity for antithrombin III, to delay intrinsic prothrombin activation for at least 15s. Heparin catalyses both thrombin and factor Xa inhibition; dermatan sulfate catalyses only thrombin inhibition, while the pentasaccharide only catalyses factor Xa inhibition. Efficient prothrombin activation, which coincided with both factor X activation and factor V proteolysis, was first observed 45s after CaC12 was added to contact-activated plasma. Heparin (approximately 0.1 microM) prolonged by at least 30 s the time required for the activation of the three clotting factors to begin. The minimum concentrations of the pentasaccharide and dermatan sulfate to delay the activation of prothrombin, factors X and V were approximately 50 microM and approximately 5 microM, respectively. Thus, each anticoagulant could inhibit intrinsic prothrombin activation only when it inhibited activation of both factors X and V. A combination of approximately 5 microM pentasaccharide and approximately 0.05 microM dermatan sulfate similarly delayed the activation of all three clotting factors. Thus, while catalysis of thrombin inhibition is a more effective pathway than catalysis of factor Xa inhibition for delaying prothrombin activation, the simultaneous catalysis of thrombin and factor Xa inhibition can synergistically improve the ability of a sulfated polysaccharide to delay prothrombin activation. PMID- 2226467 TI - The inositol-phospholipid-accelerated activation of prekallikrein by activated factor XII at physiological ionic strength requires zinc ions and high-Mr kininogen. AB - In a system consisting of purified proteins inositol-phospholipid-accelerated activation of prekallikrein by alpha-factor XIIa was determined by measuring the appearance of kallikrein amidolytic activity towards the chromogenic substrate, H D-Pro-Phe-Arg-NH-PhNO2 (PhNO2, 4-nitrophenyl). The activation reaction was ionic strength dependent. In the absence of high-Mr kininogen optimal activity was recorded at I = 50 mM. Searching for conditions, which could change this optimum towards physiological values, high-Mr kininogen was added. This resulted in an inhibition of the activity, with no change in ionic strength optimum. If, however, Zn2+ were added concomitant with high-Mr kininogen, the inhibition was abolished and optimal activity recorded at physiological ionic strength. The optimal Zn2+ concentration was found to be 0.1 mM. Kinetic analysis of the reaction demonstrated that the kcat/Km was 1.2 x 10(5) M-1 s-1 in the absence and 1.1 x 10(6) M-1 s-1 in the presence of Zn2+. Zn2+ were also required for inositol phospholipid-accelerated initiation of the contact activation in whole plasma. PMID- 2226468 TI - Activation of a serine/threonine kinase that phosphorylates microtubule associated protein 1B in vitro by growth factors and phorbol esters in quiescent rat fibroblastic cells. AB - We have previously found and characterized a mitogen-activated, serine/threonine specific protein kinase that specifically phosphorylates microtubule-associated protein 2 (MAP2) in vitro, which we call here MAP2 kinase [Hoshi, M., Nishida, E. & Sakai, H. (1988) J. Biol. Chem. 263, 5396-5401; Hoshi, M., Nishida, E. & Sakai, H. (1989) Eur. J. Biochem. 184, 477-486]. In this study, we have found another serine/threonine-specific protein kinase that is activated by various mitogens. The activated kinase utilized microtubule-associated protein 1B (MAP1B) as the major substrate in vitro, so we tentatively call it MAP1B kinase (M1BK). M1BK was maximally activated 20-30 min after treatment of quiescent rat fibroblastic 3Y1 cells with epidermal growth factor (EGF), while MAP2 kinase was maximally activated within 5-10 min of EGF treatment. The EGF-activated M1BK was eluted at about 0.15 M NaCl on a DEAE-cellulose column, while the activated MAP2 kinase was eluted at about 0.1 M NaCl under the conditions used. The EGF-activated M1BK was eluted as a single peak just after the activated MAP2 kinase on an HPLC gel filtration column. Histone, casein and ribosomal protein S6 were very poor substrates for the M1BK, while MAP2 and myelin basic protein were moderate substrates. The M1BK activity in cell extracts was inhibited by Ca2+, glycerol 2 phosphate and Zn2+, and slightly enhanced by heparin. These data suggested that M1BK is distinct from previously described mitogen-activated kinases such as MAP2 kinase, casein kinase II and S6 kinase. Pretreatment with cycloheximide or puromycin did not block the M1BK activation by EGF. Furthermore, incubation of the EGF-activated M1BK with acid phosphatase inactivated the kinase activity. Therefore, M1BK may be activated by phosphorylation in EGF-treated cells. In addition to EGF, 12-O-tetradecanoylphorbol 13-acetate, platelet-derived growth factor and insulin-like growth factor-I also induced the activation of M1BK in quiescent cells. PMID- 2226469 TI - M-phase-specific cdc2 protein kinase phosphorylates the beta subunit of casein kinase II and increases casein kinase II activity. AB - The M-phase-specific cdc2 (cell division control) protein kinase (a component of the M-phase-promoting factor) was found to activate casein kinase II in vitro. The increase in casein kinase II activity ranged over 1.5-5-fold. Increase in activity was prevented if ATP was replaced during the activation reaction by a non-hydrolysable analogue. Alkaline phosphatase treatment of the activated enzyme decreased the activity to the basal level. The beta subunit of casein kinase II was phosphorylated by cdc2 protein kinase at site(s) different from the autophosphorylation sites of the enzyme. Phosphoamino acid analysis showed that the beta subunit was phosphorylated by cdc2 protein kinase at threonine residues while autophosphorylation involved serine residues. Casein kinase II may be part of the cascade which leads to increased phosphorylation of many proteins at M phase and therefore be involved in the pleiotropic effects of M-phase-promoting factor. PMID- 2226470 TI - The role of an invariant tryptophan residue in alpha-bungarotoxin and cobrotoxin. Investigation of active derivatives with the invariant tryptophan replaced by kynurenine. AB - Ozone oxidation converted the single, invariant, tryptophan residue to N2 formylkynurenine in alpha-bungarotoxin and cobrotoxin. Upon this modification, the lethal toxicity was significantly reduced in cobrotoxin but mostly retained in alpha-bungarotoxin. Each neurotoxin containing kynurenine instead of tryptophan retained the same antigenicity as the native toxin. Fluorescence and CD spectroscopy revealed that, although the environment and state of the kynurenine residue were similar, [Kyn29]cobrotoxin was much more sensitive to pH change than alpha-[Kyn28]bungarotoxin. In terms of lethal toxicity and conformational stability, the invariant tryptophan residue appears to play a more important role in cobrotoxin, imparting a higher lethal toxicity than that in alpha-bungarotoxin, which has a disulfide bond at Cys29-Cys33. PMID- 2226471 TI - Nuclear-magnetic-resonance investigations of the biliverdin-apomyoglobin complex. AB - The recently described biliverdin-apomyoglobin complex has been investigated by two-dimensional NMR methods and molecular modeling with respect to the geometry of the chromophore and its position within the myoglobin pocket. Nuclear Overhauser effect correlations between the ligand and apoprotein amino acid residues prove that the bile pigment assumes a cyclic helical conformation and a position similar to heme in native myoglobin. PMID- 2226472 TI - Screening of natural products for antimicrobial agents. AB - Antimicrobial research is geared toward the discovery and development of novel chemical structures such as therapeutic antimicrobial agents. The continuing problem of development of resistance to existing antibacterial agents and the dearth of good antifungal agents motivates this effort toward innovation. Selection of possible new enzyme targets for antibiotic inhibition may be made on theoretical grounds, but it appears premature to select any single, previously unvalidated target for the intensive study required for rational drug design. Instead, a broad screen of chemical entities can be undertaken, dedicated to the discovery of novel antimicrobial inhibitors. A number of target areas are under investigation, including fungal mRNA splicing and bacterial DNA synthesis. A major part of the endeavor is in the historically productive area of natural product screening. To make the best use of natural product resources for the discovery of novel antibiotics, a balance is struct between screening for inhibitors of rationally chosen targets for which clinically useful inhibitors are not yet available, and screening more broadly to ensure that rare activities of unanticipated mode-of-action are not missed. PMID- 2226473 TI - Remarks on the screening of antibiotics for antibacterial activity. AB - The general principles of screening antibiotics for antimicrobial activity are similar to those for screening for other pharmacological effects. The system should be adapted to the specific character of the test substance and the objectives of the program. In the screening of beta-lactams, standard tests, such as determination of the MICs, effects of inoculum size or activity against systemic infection in mice, should be supplemented by less conventional studies on for instance activity against dormant bacteria or, in the case of penems or carbapenems, stability in the presence of kidney and lung dehydropeptidases. PMID- 2226474 TI - Screening for new agents. AB - Screening for new antiviral drugs is concentrated on a search for inhibitors of the human immunodeficiency virus, herpesviruses, influenza virus, hepatitis B virus and rhinovirus. The first step in the process is usually the screening of virus-infected cell cultures followed by secondary screening in infected animals. The relevance of the different screening methods for predicting clinical efficacy is at present uncertain due to the low number of compounds evaluated in double blind placebo-controlled clinical trials. As a consequence of the con-siderable activity in ongoing research on antiviral drugs the predictive value of the screening systems is expected to improve. PMID- 2226475 TI - Animal models as predictors of the safety and efficacy of antibiotics. AB - As opposed to the testing of safety, the testing of the efficacy of antibiotics in animals is not specified in any directives or guidelines and not explicitly required by regulatory authorities. There exists, however, no doubt that in the evaluation of new compounds testing of both safety and efficacy forms an essential link between in vitro tests and clinical trials. It is inconceivable that clinicians would be prepared to conduct a trial in patients without evidence of the efficacy of the antibiotic in question in an appropriate animal model of infection. Both the models for testing safety and those for testing efficacy suffer from a number of shortcomings. If investigators are aware of these deficiencies and take them into account when interpreting the results, the predictive value of the models can be significantly enhanced. PMID- 2226476 TI - Correlation between pharmacokinetics, pharmacodynamics and efficacy of antibacterial agents in animal models. AB - On the basis of a review of published literature it is demonstrated that pharmacokinetic parameters of antibacterial agents correlate well with therapeutic efficacy in animal models, provided pharmacodynamic parameters are taken into account. The time that serum levels exceed the MIC is the most significant parameter determining efficacy of beta-lactams, whereas the efficacy of aminoglycosides is dependent on serum concentrations and the area under the curve. The efficacy of quinolones tends to be correlated to the doses administered or drug levels achieved. However, specific pharmacodynamic properties contribute significantly to the therapeutic efficacy of a few quinolones only whereas other quinolones lack these specific pharmacodynamic attributes. Thus, the correlation of pharmacokinetic parameters with therapeutic efficacy provides important basic concepts for the design of preclinical and clinical studies in the course of which additional pharmacodynamic properties will become apparent. PMID- 2226477 TI - Basic requirements for the toxicity testing of antimicrobial agents. AB - The regulations in different countries on the toxicological testing of antimicrobial agents are similar and harmonized on an international basis. Existing requirements cover both the standard investigations performed with any other new class of therapeutic drug and investigations necessary due to the specific features of anti-infective agents. Such features are the therapeutic target (the microorganisms), the need to provide adequate treatment of patients even during clinical trials, and the potential of the drug to induce certain adverse reactions. The combination of toxicity tests used will be determined by the drug, its class and current knowledge. PMID- 2226478 TI - European standards for antibiotic susceptibility testing: towards a theoretical consensus. AB - Six different systems for antimicrobial susceptibility testing are used in Europe (BSAC, DIN, SFM, SIR, NCCLS and WRG). Breakpoints defining susceptibility or resistance of bacteria to antimicrobial agents remain the subject of discussion. Nevertheless, it is possible to establish a theoretical consensus standard list of breakpoints such that more than 95% of the breakpoints proposed by the different systems differ from the consensus standard by no more than one dilution. In general, the BSAC and DIN systems recommend lower breakpoints, and the SFM and NCCLS systems higher breakpoints than the consensus standard. Two thirds of the discrepancies are related to the breakpoints defining susceptibility. The breakpoint for susceptibility should reflect the intrinsic susceptibility of the isolate (absence of mechanisms of resistance), and the breakpoint for resistance the pharmacological potential of the drug. The scientific validation of breakpoints requires clinical verification. PMID- 2226479 TI - Prospects for standardisation of methods and guidelines for disc susceptibility testing. AB - The disc diffusion method of susceptibility testing is widely used in diagnostic laboratories throughout the world. It is simple to perform and very suited to the clinical laboratory where a single isolate can be tested with a series of antibiotics in one experiment. For these two reasons the test is by far the commonest type of susceptibility method used. Other methods such as determination of the minimum inhibitory concentration or "breakpoint" methods are used in only a small number of laboratories. If standardisation of methods is to be achieved in order to agree on uniform reporting and guidelines, methods using disc tests are of the highest priority. PMID- 2226480 TI - The regulation of biological products. AB - The purpose of regulations for biological products is the same as that for any other medicinal or related products: the protection of recipients of the products. The entry into the age of molecular biology with its attendant development and manufacturing technology has placed new demands on regulatory agencies and related industry personnel. While the general goals of regulations remain the same, the scientific bases by which biological products must be reviewed and registered vary from those traditionally used for drugs or even older vaccines produced by conventional methods of growth, harvesting and purification. New regulations must be developed which take into account the new science involved in molecular biology and recombinant technology; new definitions must be provided and widely understood. The regulation of biologic products on an international basis is complicated by issues such as national interests superceding individual patient needs, bureaucracies being driven primarily by regulation and secondarily by science, industry expecting priority treatment for innovative products while having to absorb costs related to lost regulatory review time, and agencies or industry relying upon outdated regulations and/or archaic tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226481 TI - Requirements for the documentation of pharmacokinetic properties of antimicrobial agents. AB - Proper documentation of new antimicrobial drugs for governmental registration authorities includes extensive pharmacokinetic studies. Pharmacokinetics represents the bridge between the in vitro and in vivo phases of drug development. Both healthy human volunteers and patients must be studied, the former during the initial stages of the pharmacokinetic studies. The documentation should give information on the following: absorption from the gastrointestinal tract, bioavailability, pharmacokinetic model, impact of increasing doses (oral and intravenous), metabolism, routes and degree of elimination, interaction with food and other drugs, impact of the steady state, and serum protein binding. Basic pharmacokinetic parameters used are the serum half-life, clearance, distribution volume and dose dependence. The bioavailability of oral doses must be determined using the same dose sizes and subjects. Data on extravascular penetration should also be included in complete documentation. Key diseases in which the pharmacokinetics should be studied are reduced renal and liver function, heart failure, pregnancy, cystic fibrosis and intestinal diseases. The consequences of low age (e.g. newborns) and old age also require some attention. PMID- 2226483 TI - Studies on the ecological impact of antibiotics. AB - The presence of an antibiotic in the intestinal tract as a result of oral administration or intestinal excretion can have a pronounced impact of the microflora. Studies of the effect on the intestinal microflora and faecal excretion should therefore be carried out in volunteers and patients when new antibacterial agents are evaluated. These two analyses should be combined in the evaluation. PMID- 2226482 TI - Significance of tissue levels for prediction of antibiotic efficacy and determination of dosage. AB - Determination of tissue levels is widely thought to provide useful information in the investigation of a new antibiotic, however this assumption is not fully justified. In this paper the following questions are covered. Firstly, the methodological problems encountered in the measurement of antibiotic levels in solid tissues and extravascular fluids are described. Secondly, the difficulties encountered in interpreting tissue concentrations are discussed, given the heterogeneity of distribution of drugs, potential intracellular penetration, binding to tissue proteins and local factors reducing antibacterial activity. Thirdly, the respective importance of animal and human data on tissue levels for prediction of efficacy is analysed. In some animal models it is possible to study the conditions affecting antibacterial activity and to obtain data relevant to the clinical situation. However, the inoculum effect, the metabolism of bacteria, the mechanism of the bactericidal action of drugs and the type of infected tissue are important factors to be taken into account. In humans, data obtained from infected tissue is sparse and contributes little to knowledge. Knowledge of tissue levels may be important for establishing whether data obtained in animals can be applied to humans or not. Fourthly, the importance of tissue levels in determining antibiotic dosages is evaluated. In humans, tissue levels are of limited value in the determination of unitary dose and dosage intervals in relation to the clinical response. Trough serum levels of free drug, half-life at the beta-phase and rate of in vitro killing are the most important parameters to be considered. Their relative importance depends mainly on the mode of action of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226484 TI - Good clinical practice. AB - Good Clinical Practice (GCP) is a quality assurance system dealing with all stages of clinical trials which is progressively being adopted by European countries. European GCP guidelines are in preparation and will be issued soon. However, implementation of the guidelines poses major and costly problems. The training of investigators, the proper functioning of research ethics committees, the practice of obtaining written informed consent, source data verification, and quality control with internal audit and official inspections are among the most difficult issues. The obvious benefits of GCP are the improved quality of clinical trials and of data generated by such trials, as well as mutual recognition of studies conducted abroad. PMID- 2226485 TI - The design of clinical trials with antibiotics. AB - Clinical trials to test antibiotics are normally of a less than satisfactory quality. Examples of common errors in the design and execution of trials with antibiotics are inclusion of too few patients to allow conclusions to be drawn, open uncontrolled design leading to a risk of considerable investigator bias, and inclusion of heterogeneous patient samples. This article suggests minimum requirements for antibiotic studies. Guidelines for such trials are needed and should have the widest possible international application in order to permit studies involving centres in various countries and to reduce the costs for development of new drugs. PMID- 2226487 TI - Evaluation of methods for recording adverse drug reactions in clinical trials. AB - Four methods used for obtaining information from patients on adverse drug reactions are reviewed on the basis of personal experience. In the development of new therapeutic drugs the method which records all events experienced by a patient during drug treatment is to be preferred as it increases the possibility of detecting unanticipated or previously unreported adverse reactions. Disadvantage of this method is that a high number of events not related to drug treatment may be recorded, causing problems in analysis of the data. PMID- 2226486 TI - Evaluation of safety and tolerance in clinical trials with antimicrobial agents. AB - In this review the general and specific difficulties encountered in the evaluation of safety and tolerance of antimicrobial agents in clinical trials are discussed. In addition to the usual pharmacological and toxicological effects (adverse drug reactions) occurring in individual patients, microbiologically induced side-effects also have to be considered. The different methods for registration of side-effects and their limitations are discussed. A system is proposed for evaluation of the cause/effect relationships of adverse drug reactions. A system is also discussed for the evaluation of the severity of adverse drug reactions, and different classifications are presented. PMID- 2226488 TI - Regulatory requirements for clinical evaluation of antimicrobial agents. AB - Evaluation of antimicrobial agents in governed mainly by interaction between the pharmaceutical industry and regulatory authorities. The 1977 FDA guidelines have been setting the standards for more than a decade now. Basic principles of the 1977 guidelines remain valid, however changes in the definition of end-points of response, as measured by both clinical and microbiological criteria, have occurred. The new (draft) FDA guidelines and the 1989 guidelines of the British Society of Antimicrobial Chemotherapy are more consistent with contemporary concepts of treatment. In general, the differences in the requirements are minimal with a few exceptions, namely the requirements concerning blinding and assessment of clinical efficacy by site of infection and by organism in the FDA guidelines. PMID- 2226489 TI - The clinical evaluation of antibacterial drugs: guidelines of the British Society for Antimicrobial Chemotherapy. AB - Anti-infective agents differ in several respects from other classes of therapeutic drugs. They are aimed at the treatment or prevention of infection which can occur at several body sites and be caused by a wide range of microorganisms. The infectious process frequently modifies metabolic behaviour which in turn may affect the pharmacology of an agent. In addition, the issue of drug resistance raises concerns in individual patients, hospital units and the broader community. The difficulties in scientifically validating the clinical efficacy and safety of anti-infective drugs led to the Report on the Clinical Evaluation of Antibacterial Drugs of the British Society for Antimicrobial Chemotherapy. The report identifies general principles relevant to the study of these drugs in man and identifies the major microbiological and clinical considerations. Detailed comments on the conduct of pharmacokinetic studies and therapeutic trials are provided with particular emphasis on design, definitions, execution and analysis. Adverse event monitoring, assessment of severity and determination of causality are also reviewed. Pharmaco-economic considerations are identified as a significant issue for the future. The revision of the 1977 FDA guidelines on anti-infective drug development provides the opportunity to harmonise these issues, particularly within the major markets of North America, Europe and Japan. PMID- 2226490 TI - Guidelines of the World Health Organization for clinical trials with antimicrobial agents. AB - The WHO Consensus Documents Series on Clinical Investigation covers many different therapeutic drug groups including the antibacterial drugs. The documents have been produced by the WHO Regional Office for Europe in collaboration with a wide group of clinicians and other experts in order to define and promote agreement on current and emerging standards for the clinical investigation of drugs. PMID- 2226491 TI - The implications for Europe of revised FDA guidelines for clinical trials with anti-infective agents. AB - This article summarizes the current collaborative effort between the US Food und Drug Administration and the Infectious Diseases Society of America for the purpose of generating new General and Disease/Organism Specific Guidelines for the evaluation of anti-infective agents. Examples of proposed changes from draft documents are presented. The final documents may assist European colleagues in their efforts to establish a standardized new drug registration process by 1992. An area of mutual interest is the acceptability of safety and efficacy data from international clinical trials. In the interest of human and financial economies, both US and European Guidelines need to clarify the conditions, or criteria, for the conduct of valid 'off-shore' clinical trials. PMID- 2226492 TI - Use of a ribosomal RNA gene probe for the epidemiological study of methicillin and ciprofloxacin resistant Staphylococcus aureus. AB - Conventional bacteriophage typing was combined with ribotyping in the analysis of methicillin and ciprofloxacin resistant Staphylococcus aureus strains isolated in increasing frequency since the introduction of the new 4-quinolones as therapeutic agents in the Tel-Aviv Medical Center. Whole-cell DNA was digested with EcoRI and HindIII restriction endonucleases. Agarose gel electrophoresis, Southern blotting, and hybridization by biotinylated probe DNA coding for ribosomal RNA revealed 7 to 14 bands. Analysis of the patterns established a single DNA type in EcoRI as well as in HindIII digests for all strains except one. Control strains from other sources differed in their band patterns. Bacteriophage typing confirmed the results of DNA typing. Thus, the frequent occurrence of staphylococcal isolates resistant to 4-quinolones in the hospital was not due to mutational development of resistance in many strains, but to the spread of a resistant strain. PMID- 2226493 TI - Blood culture techniques for the diagnosis of melioidosis. AB - The effects of variations in laboratory technique on the speed and sensitivity of isolation of Pseudomonas pseudomallei from blood were evaluated prospectively. Pseudomonas pseudomallei was isolated from 154 of 546 cultures from 325 patients with suspected or confirmed melioidosis. Subcultures after 12 to 24 and 36 to 48 hours of incubation were positive in 52.3% and 80.8% respectively. The yields from 20 ml (blood to broth ratio 1:4) and 50 ml (blood to broth ratio 1:10) brain heart infusion broth bottles were equivalent in patients not receiving treatment for melioidosis. During therapy, the 50 ml bottles grew Pseudomonas pseudomallei significantly faster than the 20 ml bottles (p less than 0.01), and gave a higher overall yield for cultures processed in antimicrobial removal devices (p less than 0.05). These devices themselves increased the speed of isolation of the organism from treated patients (p less than 0.01). In most cases, all bottles collected from a patient before treatment were positive, and a single 20 ml bottle had an estimated relative sensitivity of 85.7% (95% confidence interval 77.1-94.3%). Early subculture should be employed routinely for the laboratory diagnosis of septicaemic melioidosis. However, blood culture techniques do not need to be sophisticated. Culture of 5 ml blood in 20 ml broth is a simple and sensitive procedure suitable for regions where melioidosis is currently under diagnosed. PMID- 2226494 TI - Histopathological method for diagnosis of cryptosporidiosis using monoclonal antibodies. AB - A monoclonal antibody directed against the oocyst wall of Cryptosporidium parvum was produced which strongly reacted with 25 strains of the parasite. This antibody was assessed for use in a diagnostic immunoperoxidase assay performed on tissue sections. It permitted an intense and specific staining of the parasite in five biopsies positive for Cryptosporidium parvum fixed with routine techniques. The procedure described may be useful in screening mucosal biopsies from immunosuppressed patients. PMID- 2226495 TI - Evaluation of two media for antibiotic susceptibility testing of anaerobic bacteria using the receiver operating characteristic procedure. AB - Wilkins-Chalgren agar and Meat-Yeast agar were evaluated as media for antibiotic susceptibility testing using 112 anaerobic bacterial strains. The results obtained with the two media using the diffusion method were compared with those obtained by the dilution method as reference method. The results were analyzed by the receiver operating characteristic (ROC) procedure allowing a graphic representation of sensitivity and specificity of the technique for each cut-off value. The area under the ROC curves was calculated to compare the accuracy of the two methods. Six antibiotics were tested including amoxicillin, cefoxitin, piperacillin, doxycycline and clindamycin. For amoxicillin and clindamycin, the two methods showed a high and identical discriminative power for distinguishing susceptible bacteria from the others. Diffusion in Wilkins-Chalgren agar appeared better than diffusion in Meat-Yeast agar for separating resistant bacteria from bacteria of intermediate susceptibility (amoxicillin p less than 0.005; clindamycin p less than 0.04). For other drugs, diffusion in Wilkins-Chalgren agar always had a discriminative power higher than that obtained with diffusion in Meat-Yeast agar for separating susceptible bacteria from the others (cefoxitin p less than 0.0005; piperacillin p less than 0.02; doxycycline p less than 0.05). The Wilkins-Chalgren agar medium thus appeared superior to the Meat-Yeast agar medium using the ROC evaluation method, which would deserve wider utilization in the field of microbiology. PMID- 2226496 TI - Onset of ocular complications in congenital toxoplasmosis associated with immunoglobulin M antibodies to Toxoplasma gondii. AB - Four patients with congenital toxoplasmosis serologically diagnosed by the Sabin Feldman test (SFT) and the IgM-indirect fluorescent antibody test (IgM-IFAT) in the first year of life presented with eye disease between the age of 21 months and ten years. Repeated serological testing revealed increasing levels of specific antibodies as measured by the SFT. IgM antibodies to Toxoplasma gondii were detected in all four patients by the immunosorbent agglutination assay, in two by the IgM-IFAT and in three by the IgM-indirect haemagglutination test. Findings suggest that specific IgM antibodies reappear at the time of reactivation of congenital toxoplasmosis later in life, or possibly persist for an extraordinary long period (up to ten years). PMID- 2226497 TI - Evaluation of a line immunoassay for the differential detection of antibodies to human immunodeficiency virus. AB - A newly introduced single strip line immunoassay was evaluated as a possible alternative to Western blot for the differential detection of antibodies to multiple HIV-1 and HIV-2 antigens in human serum. In a panel of 153 sera found to be positive twice in currently used screening tests, the line immunoassay and the Western blot detected 44 true positive results. Using Western blot as reference method, the line immunoassay gave 100% specificity and sensitivity. These results suggest that the line immunoassay may be a viable alternative to Western blot. PMID- 2226498 TI - Comparative in vitro activity of cefpirome and cefepime, two new cephalosporins. AB - In in vitro tests the broad-spectrum cephalosporins cefpirome and cefepime were highly active against Enterobacteriaceae, although often less so against strains resistant to amoxicillin-clavulanate and ticarcillin-clavulanate, and against most strains of Acinetobacter spp. and Aeromonas hydrophila. They were also active against Pseudomonas aeruginosa, although strains with non-plasmid mediated beta-lactam resistance were sometimes less sensitive. Other Pseudomonas spp. varied in their sensitivity. Both agents were highly active against Haemophilus influenzae, but beta-lactamase-producing Branhamella catarrhalis were somewhat less sensitive. Neisseria gonorrhoeae were susceptible, although non-beta lactamase producing penicillin-resistant strains had higher MICs. Gardnerella vaginalis was also susceptible and Campylobacter coli/jejuni usually susceptible. Both antibiotics had good activity against Staphylococcus aureus and coagulase negative staphylococci except for methicillin-resistant strains and Staphylococcus haemolyticus which were of borderline sensitivity. All streptococci were sensitive, with the exception of highly penicillin-resistant pneumococci and enterococci against which cefpirome had greater activity than cefepime. Both antibiotics had little useful activity against the Bacteroides fragilis group or Bacteroides oralis group but were active against most other anaerobes. Clostridium difficile and some other Clostridium species were resistant. PMID- 2226500 TI - In vitro susceptibility of Helicobacter pylori to the new oral cephalosporins cefpodoxime, ceftibuten and cefixime. AB - The in vitro activity against 30 Helicobacter pylori strains of three new third generation cephalosporins, cefpodoxime, ceftibuten and cefixime, which can be administered orally, was determined using an agar dilution technique under microaerophilic conditions. The MIC50 and MIC90 of cefpodoxime was 0.5 and 4.0 micrograms/ml respectively, of ceftibuten 2.0 and 8.0 micrograms/ml, and of cefixime 0.06 and 0.5 microgram/ml. All antibiotics showed good activity against Helicobacter pylori, cefixime having the highest activity of the three agents. PMID- 2226499 TI - In vitro activity and beta-lactamase stability of the new oral cephalosporin Bay v 3522. AB - The activity of the new oral cephalosporin Bay v 3522 was compared to that of six other beta-lactam agents. Bay v 3522 inhibited methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis at less than or equal to 2 micrograms/ml, compared to MICs of greater than or equal to 8 micrograms/ml for the other cephalosporins tested. It was more active against Streptococcus pyogenes (MIC less than or equal to 0.06 microgram/ml) than cefuroxime, cefixime, cephalexin and cefaclor. Groups B, C and G streptococci were inhibited at less than or equal to 0.12 microgram/ml, while the MI"90 for Streptococcus bovis and viridans streptococci was 0.5 and 2 micrograms/ml, respectively. The MIC90 for enterococci and Listeria monocytogenes was 8 micrograms/ml. Clostridium perfringens was inhibited by 0.12 microgram/ml, but most Bacteroides spp. were resistant. The MIC90 for beta-lactamase positive Escherichia coli (producing primarily TEM-1) was greater than 64 micrograms/ml and for beta-lactamase negative strains 16 micrograms/ml. The MIC90 for high-level beta-lactamase producing Klebsiella pneumoniae was greater than 64 micrograms/ml versus 4 micrograms/ml for other isolates. The MIC90 for Moraxella catarrhalis was 2 micrograms/ml, for Haemophilus influenzae 1 micrograms/ml, and for Neisseria gonorrhoeae 4 micrograms/ml. Enterobacter cloacae, Citrobacter freundii, Proteus mirabilis, Providencia spp. and Pseudomonas aeruginosa were resistant. Bay v 3522 was destroyed by TEM-1, SHV-1, TEM-3 and P99 beta-lactamases. PMID- 2226501 TI - In vitro activity of the new semi-synthetic polypeptide cilofungin (LY121019) against Aspergillus and Candida species. AB - The in vitro activity of cilofungin (LY121019), a new semi-synthetic antifungal agent was evaluated. Potent activity was seen against Candida albicans and Candida tropicalis, with almost identical MIC and MFC results, whereas no activity was seen against any isolates of Candida parapsilosis or three Aspergillus spp. However, MICs were dependent on medium and test conditions chosen. It is concluded that cilofungin has good activity against some medically important yeasts in vitro, and that its in vitro activity depends on the method used. PMID- 2226502 TI - Peritonitis caused by Actinomadura madurae in a patient on CAPD. PMID- 2226503 TI - Reactivation of hepatitis B virus in a previously immune patient with human immunodeficiency virus infection. PMID- 2226504 TI - Reentry revisited. PMID- 2226505 TI - Early appearance of 2,3-butanediol in acute myocardial infarction. A new marker for ischaemia? AB - In 28 patients with acute myocardial infarction, the release pattern of 2,3 butanediol (BD), a product of intermediary metabolism, and creatine kinase activity (CK) in blood were compared. Whereas CK at entry was low in all patients, the BD level was elevated in 18 (64%). However, BD returned to normal levels during the next 24 h whereas CK increased. The BD level at entry did not allow differentiation between patients with transmural or non-transmural infarction; it was independent of clinical findings and biochemical parameters. We suggest that, in patients with acute myocardial infarction, elevated levels of BD originates from myocardial metabolism. Whether it reflects ongoing ischaemia or reperfusion of the infarcted area remains unresolved. PMID- 2226506 TI - Polymorphonuclear leucocytes as potential source of free radicals in the ischaemic-reperfused myocardium. AB - The feasibility of polymorphonuclear leucocytes as a potential source of free radicals during reperfusion of ischaemic myocardium was evaluated. Isolated rat heart was perfused in the presence of f-Met-Leu-Phe-activated and normal polymorphonuclear leucocytes for 30 min. To judge the degree of cellular injury which might result from activated polymorphonuclear leucocytes during perfusion, isolated hearts were also perfused with superoxide anions, hydroxyl radicals, and hypochlorous acid-generating systems in the absence or presence of their corresponding scavengers, superoxide dismutase plus catalase, dimethylthiourea, and allopurinol, respectively. Activated polymorphonuclear leucocytes stimulated the release of lactate dehydrogenase, a biological marker of cellular injury, and malondialdehyde, a presumptive marker for lipid peroxidation; increased tissue injury, as evidenced by morphologic examinations using light and electron microscopy; decreased dry/wet ratios of heart, signifying oedema formation; and reduced myocardial adenosine triphosphate and creatine phosphate content as well as coronary flow, indicating decreased myocardial performance. These biological, physiological, and morphologic parameters were reversed significantly, but not completely, by treating the heart with scavengers, superoxide dismutase plus catalase or allopurinol, but were reversed completely by simultaneous treatment with superoxide dismutase, catalase, and allopurinol. Comparable results were obtained when the hearts were treated with each of these free radical-generating systems and their corresponding scavengers. Generation of free radicals was confirmed either by cytochrome c reduction or by examining the chemiluminescence response using a luminometer. These results indicate that activated polymorphonuclear leucocytes can cause myocardial cellular injury equivalent to the damage caused by free radicals and oxidants which are present in an ischaemic reperfused heart, suggesting that polymorphonuclear leucocytes may be a potential source of free radicals in the reperfused heart. PMID- 2226507 TI - Increased neutrophil aggregability in coronary artery disease. AB - The purpose of this investigation was to study neutrophil (PMN) aggregation in the aorta and coronary sinus of 20 patients with angiographically documented coronary artery disease (group I) compared with eight patients with normal coronary arteries (group II). PMNs were separated from the other blood components and their aggregation response to Ca2+ ionophore A 23187 l x 10(-5) M (final concentration) was measured. Group I patients had higher aggregating activity in the coronary sinus than in the aorta (24.9 +/- 3.7 vs 18.7 +/- 3.4 average maximum delta T, P less than 0.01), while no difference was found in group II (coronary sinus 16.7 +/- 3.5; aorta 16.3 +/- 2.4 average maximum delta T P = NS). Among group I patients, smokers had a significantly higher aggregating activity than non-smokers, whereas no correlation was found between aggregation response and blood cholesterol values. These data suggest that the presence of atherosclerotic plaques in coronary vessels may prime PMNs so that they show greater aggregating response to subsequent stimulation. PMID- 2226508 TI - Factors predicting mortality in idiopathic dilated cardiomyopathy. AB - A study of factors predicting mortality was performed in 201 patients with dilated cardiomyopathy (163 men, 38 women, mean age: 48 +/- 11 years) by multivariate analysis (Cox Model) of 51 clinical, electrocardiographic, echocardiographic and haemodynamic parameters, 56 patients died during follow-up (mean follow-up: 57.1 +/- 29.9 months). 5 year survival was 77 +/- 3%. The following parameters were independent predictors of mortality: first symptom: pulmonary oedema, peripheral oedema, syncope; duration of symptoms at the time of inclusion; end systolic left ventricular volume; end diastolic left ventricular diameter; pulmonary artery systolic pressure; and their combination had the most accurate predictive value for death. A quantitative score (s) was calculated and used to define three subgroups: A:s less than or equal to 4.5; B: 4.5 less than s less than 6; C:s greater than or equal to 6. Five-year survival was 90 +/- 5% in group A; 84 +/- 4% in B and only 53 +/- 7% in C. In conclusion, overall survival was good in this population of all stage dilated cardiomyopathy; factors related to clinical severity, left ventricular dilation, systolic pulmonary artery pressure and duration of symptoms defined a subgroup of patients with poor prognosis. PMID- 2226509 TI - Cardiac evaluation of candidates for kidney transplantation: value of exercise radionuclide angiocardiography. AB - In view of the high incidence and mortality of coronary artery disease (CAD) in patients with kidney transplantation, a systematic cardiac evaluation was prospectively performed in 103 uraemic patients eligible for transplantation. After clinical examination, 28 patients with symptoms of CAD or diabetes mellitus were referred directly for coronary angiography, whereas the remaining 75 patients had rest and exercise radionuclide angiocardiography for evaluation of possible asymptomatic CAD. Among them, left ventricular ejection fraction was below 40% at rest or fell during exercise by at least 5 EF% in 12 patients; coronary angiography in nine showed CAD in four and hypertensive heart disease in five. In the remaining 63 (of 75) patients without severe resting left ventricular dysfunction or exercise ischaemia, the follow-up of 28 +/- 7 months revealed no clinical manifestation of CAD. Overall incidence of CAD in symptomatic and asymptomatic patients during a follow-up of 27 months after cardiac evaluation was 20 and 25% in nondiabetic and diabetic candidates for kidney transplantation, respectively (P = n.s.). Thus, clinical examination combined with exercise radionuclide angiocardiography in patients without signs or symptoms of heart disease had a high predictive accuracy for presence or absence of late manifestations of CAD. Exercise radionuclide angiocardiography is therefore a useful method for screening kidney transplantation candidates for asymptomatic CAD. PMID- 2226510 TI - Doppler evaluation of left ventricular filling: effect of verapamil on non obstructive hypertrophic cardiomyopathy. AB - Impaired left ventricular (LV) filling is known to be a major determinant of non obstructive hypertrophic cardiomyopathy (HCM). Seventeen patients with non obstructive HCM (mean age 71 years) were investigated by Doppler echocardiography, before and after oral treatment with verapamil (mean daily doses: 335 mg). Diagnosis was based on clinical and echocardiographic data. Mitral regurgitation was absent or mild. Heart rate, PQ interval and mitral regurgitation did not change after treatment. All calculated values of Doppler LV filling improved significantly: corrected relaxation time, ratio of atrial to early velocity, EF slope and pressure half-time (P less than 0.005) showed more significant differences than more sophisticated indices using time-velocity integrals of Doppler LV filling flow (P less than 0.005). Results appear to reflect an effect of verapamil on LV relaxation; a slight effect of a modified load was nevertheless not excluded. We conclude that all parameters of Doppler LV filling show marked improvement in this elderly group with non-obstructive HCM, after oral verapamil. Doppler echocardiography is an easy and useful clinical method to assess the effect of a drug on ventricular relaxation of non obstructive HCM. PMID- 2226511 TI - Hepatic venous connection to a persistent inferior caval vein in left isomerism. AB - In 22 cases of left atrial isomerism studied at the Brompton Hospital, four cases were found to have an unusual arrangement of the abdominal vessels. There was persistence of an inferior caval vein, partially anomalous hepatic venous connection and additional continuation of part of the venous return from the lower body through the azygos venous system. This venous pattern had surgical implications in our index case, since redirection of the inferior caval venous return was necessary. PMID- 2226512 TI - Giant intrapericardial aneurysm of the left atrial appendage. AB - A young patient is reported with an aneurysm of the left atrial appendage having supraventricular arrhythmias and a period of chest pain accompanied by a rise in cardiac enzymes. Compression of the left anterior descending coronary artery by the aneurysm was felt to be responsible for the myocardial injury. PMID- 2226513 TI - Malignant thymoma causing tricuspid valve obstruction. AB - A 57-year-old man presenting with a retrosternal mass was found to have a malignant thymoma. This was treated with surgery and radiotherapy. It recurred 5 years later as an intra-cardiac mass causing tricuspid valve obstruction. PMID- 2226514 TI - AV nodal reentrant tachycardia using three different AV nodal pathways. AB - In a patient with frequent paroxysmal supraventricular tachycardia, an electrophysiologic study was performed. Although by programmed atrial stimulation only double AV nodal pathways could be documented, three distinct forms of AV nodal reentrant tachycardia could be induced. By programmed atrial stimulation a typical AV nodal reentrant tachycardia was initiated, by programmed ventricular stimulation, an AV nodal reentrant tachycardia was induced with an antegrade conduction time of 215 ms and a retrograde conduction time of 160 ms. Furthermore, a third form of tachycardia was induced with alternating cycle length due to two different antegrade conduction times, whereas retrograde conduction time was almost identical, irrespective of the antegrade conduction time. The patient received betaxolol (20 mg day-1); during a second electrophysiologic study, the tachycardia could not be induced, and it did not occur spontaneously during a follow-up period of 14 months. PMID- 2226515 TI - Transthoracic and transoesophageal echocardiographic documentation of disappearance of massive right atrial and pulmonary artery thromboemboli after fibrinolytic therapy and normalization of left ventricular dimensions and function. AB - In this paper, we report a case of dilated cardiomyopathy with right atrial thrombi and pulmonary artery thromboemboli, in which regression of thromboemboli followed fibrinolytic therapy, and normalization of left ventricular dimensions and function were documented at echocardiographic follow-up. The important role of transoesophageal echocardiography in diagnosis and follow-up of right intracavitary masses and thromboemboli in the main pulmonary arteries is discussed, as is the role of echocardiography in follow-up of cardiomyopathy. PMID- 2226516 TI - Lipoproteins and the pathobiology of the arterial intima. The ninth Paavo Nurmi symposium. 7-9 September 1989, Porvoo, Finland. Proceedings. PMID- 2226517 TI - Malondialdehyde, modified lipoproteins, and atherosclerosis. PMID- 2226518 TI - Macrophage uptake of cholesterol-containing particles derived from LDL and isolated from atherosclerotic lesions. AB - A variety of different cholesterol-rich particles with different physical and chemical structures can be isolated from human atherosclerotic lesions. Many of these particles are internalized in an unregulated fashion by macrophages in culture, leading to lipid loading of these cells. However, the in vivo relevance of this uptake is still uncertain. In this overview, we have summarized data obtained primarily in our laboratory on low density lipoprotein (LDL)-like particles (A-LDL) and large cholesterol-rich droplets isolated from human atherosclerotic lesions. Based on our studies, we propose a variety of different mechanisms of uptake. A-LDL can be internalized by the LDL receptor or the scavenger receptor on macrophages in culture; the latter uptake mechanism can lead to lipid loading. In addition, at high concentrations A-LDL can undergo aggregation, possibly due to intermolecular cross-bridging by aldehydes released during oxidation of these particles. The aggregates are subsequently internalized by macrophages by phagocytosis, a process which appears to be independent of the LDL or scavenger receptor. By contrast, arterial smooth muscle cells do not take up these aggregates. Large cholesteryl ester-rich particles isolated from human lesions, and derived from LDL that had been degraded by hydrolytic enzymes in the extracellular space of the arterial wall, or from inclusions released from lysed foam cells, are also internalized via phagocytosis by macrophages in culture. Since some of these particles contain apoliproteins and/or proteins that are ligands for receptors on macrophages, initial receptor-mediated binding may precede and facilitate subsequent phagocytosis in some cases. Uptake of the diverse group of cholesteryl ester-rich particles in plaques can induce lipid loading of macrophages and therefore may lead to further growth of the atherosclerotic plaque. PMID- 2226519 TI - Macrophages and ceroid in human atherosclerosis. AB - It is proposed that atherosclerosis is a chronic inflammatory disease in which monocyte-derived macrophages are doing harm and smooth muscle cells are essentially reparative. Activities of macrophages that might be contributory to the development of atherosclerosis are tabulated. Observations and experiments are described that suggest macrophages may be contributing to lipoprotein oxidation within the plaque and that individual humans vary in their macrophage oxidative capacity. The possibility of intervention with antioxidants is discussed. PMID- 2226520 TI - The role of oxidized low density lipoprotein in the pathogenesis of atherosclerosis. AB - Recently, it has been suggested that oxidized low density lipoprotein (LDL) plays an important role in atherogenesis by facilitating the accumulation of lipids in macrophages. In vitro studies from our laboratory have shown that oxidized LDL is recognized not only by a specific receptor, but also by a receptor which recognizes both oxidized LDL and acetyl LDL. Probucol, originally developed as an antioxidant, prevents the oxidative modification of LDL in vitro. Our recent studies show that probucol prevents the progression of atherosclerosis in homozygous WHHL rabbits in vivo without any changes in plasma LDL cholesterol levels. These results strongly suggest that oxidative modification of LDL could occur in vivo and probucol could slow the progression of atherosclerosis, especially the foam cell-rich fatty streak lesions, without changing plasma cholesterol levels. PMID- 2226521 TI - Lipoprotein metabolism of human and rabbit arterial cells in primary culture. AB - The early atherosclerotic lesion, the fatty streak, consists of cholesteryl ester containing foam cells originating mainly from monocyte-macrophages and to a lesser extent from smooth muscle cells. In this study, we describe lipoprotein uptake and cholesterol accumulation into enzyme-dispersed primary cell cultures from cholesterol-fed rabbit aortas and human aortic fatty streaks. Uptake of fluorescently labelled acetylated low density lipoprotein (acetyl-LDL) was demonstrable in macrophage-derived foam cells and in many smooth muscle cells in early primary cultures. The uptake of acetyl-LDL led to significantly enhanced cellular esterification of cholesterol. Fluorescent beta-migrating very low density lipoprotein (beta-VLDL) was internalized by a considerable number of lesion macrophages and also by smooth muscle cells. Also beta-VLDL uptake stimulated cholesterol esterification, although the effect was milder than that of acetyl-LDL. These findings lend support to the assumption that, during atherogenesis, arterial macrophages are capable of accumulating cholesteryl esters by receptor-mediated uptake of beta-VLDL and modified LDL. The internalization of modified LDL by smooth muscle cells represents a mechanism potentially contributing to the formation of foam cells in the atherosclerotic lesion. PMID- 2226522 TI - The metabolism of low density lipoproteins by rat serosal mast cells. AB - Rat serosal mast cells contain secretory granules composed of a heparin proteoglycan matrix in which neutral proteases are embedded. Stimulation of the mast cells leads to granule exocytosis and formation of two pools of granules located extracellularly, firstly, granules expelled into the 'free' extracellular space and ultimately phagocytosed by the scavenging cells in the vicinity of mast cells and, secondly, granules which remain associated with their parent mast cells, and become internalized by them during recovery from stimulation. If mast cells are stimulated in the presence of macrophages in a low density lipoprotein (LDL)-containing medium, LDL is bound to the heparin proteoglycan component of the exocytosed granules whether they are expelled into the 'free' extracellular space or remain associated with the mast cells. The granules located in the 'free' extracellular space degrade, by the action of their neutral proteases, the apolipoprotein B component of the bound LDL. The proteolytic degradation of the granule-bound LDL results in its modification such that large fused LDL particles are formed on the granule surface. Phagocytosis, by macrophages, of the granules containing fused LDL particles leads to lysosomal degradation of LDL and cholesterol accumulation in macrophages as non-membrane-bound cholesteryl ester droplets, typical of foam cells. In contrast, the rapid internalization of the LDL-bearing, mast-cell-associated granules by recovering mast cells is not followed by lysosomal processing of LDL. Instead, it leads to cholesterol accumulation in mast cells, in the form of large, partially degraded, modified LDL particles, in the granule compartment. PMID- 2226523 TI - Arterial wall proteoglycans--biological properties related to pathogenesis of atherosclerosis. AB - The arterial wall is a complex organ system with respect to carbohydrate-protein macromolecules, particularly proteoglycans. Proteoglycans in the arterial wall display polydispersity and heterogeneity even in the same family. At least two major types are known: chondroitin sulphate-dermatan sulphate type and heparan sulphate type. These proteoglycans have varied biological properties, and some of these properties are implicated in the development of atherosclerosis. The chondroitin sulphate-dermatan sulphate proteoglycans are capable of forming complexes with serum low-density lipoproteins, a process conductive to lipid accumulation in the extracellular space of the arterial wall. Also, such reactions render low-density lipoprotein particles electronegative aggregates. These altered low-density lipoproteins are taken up by macrophages (and possibly by proliferative smooth muscle cells) through a high-affinity receptor pathway devoid of feedback regulation, which results in intracellular lipid accumulation and foam-cell formation, a hallmark of atherosclerosis. On the other hand, heparan sulphate proteoglycan located on the cell surface and internal elastic lamina is antithrombogenic, and facilitates binding of the lipid-clearing enzyme, lipoprotein lipase, to endothelium. Thus, chondroitin sulphate and heparan sulphate proteoglycans with divergent biological properties play a crucial role in the pathogenesis of atherosclerosis. PMID- 2226524 TI - Transfer of lipoproteins from plasma to the cell populations of the normal and atherosclerotic arterial tissue. AB - It appears that retention of lipoproteins rather than increased influx is the basis for lipoprotein deposition in arterial tissue during atherogenesis. Binding of lipoproteins to arterial proteoglycans is mediated by a peptide sequence considered to be involved in the interaction between the lipoproteins and the lipoprotein receptor. Consequently, in the presence of an excess of arterial proteoglycan, receptor-mediated cellular uptake of LDL is inhibited. However, LDL which has been precipitated by proteoglycan and subsequently resolubilized is taken up more avidly than native LDL, both in macrophages and in smooth muscle cells. This appears to be due to selection by the proteoglycans of a more reactive fraction of LDL. This fraction has a smaller molecular size and less surface phospholipids. As smaller LDL particles also have a higher transfer rate into the arterial tissue they may be particularly atherogenic. Low density lipoproteins appear to be taken up with higher affinity by arterial macrophages than by smooth muscle cells. The selective transfer of the LDL to macrophages can be inhibited by alpha-tocopherol, suggesting that oxidative modification may be involved in this process. The role of foam cells in atherogenesis is discussed in the context of the energy requirements of the arterial wall. PMID- 2226525 TI - Molecular basis of the association of arterial proteoglycans with low density lipoproteins: its effect on the structure of the lipoprotein particle. AB - Modifications of low density lipoproteins (LDL) that enter the arterial intima appear to be responsible for their eventual extracellular and intracellular accumulation during atherogenesis. Some of these modifications seem to be the result of LDL association with intimal chondroitin sulphate-rich proteoglycans (CSPG). We have used frontal elution affinity chromatography, binding and competition experiments with synthetic segments of apoB-100 to better define the ligand regions for the LDL-CSPG complexes. The minimum structural requirement for recognition by the CSPG appears to be a hydrophilic nine-residue amino-acid segment with five lysine and arginine residues. Analysis of other similar regions in apoB-100 and other glycosaminoglycan-binding proteins suggest that besides a cluster of positively charged amino-acids, the presence of hydroxyl-containing residues favours the association with sulphated proteoglycans. With controlled proteolytic hydrolysis, we found that the interaction of LDL with CSPG modifies the surface accessibility of a apoB-100 segments containing arginine and lysine. Because these apoB-100 domains may also be involved in cell-receptor binding, the CSPG-induced modifications could be the structural explanation for the observed increase in cellular uptake of proteoglycan-modified LDL. PMID- 2226527 TI - Extracellular lipid deposition in atherosclerosis. AB - Atherosclerotic lipid deposits found in the core region of fibrous plaques are almost entirely extracellular, but it is not known whether they are derived from necrosis of cells containing accumulated lipid or from direct extracellular lipid accumulation. New evidence pertaining to this question has been obtained through the use of recently developed techniques for preserving and staining lipids in electron microscopy, and through a detailed morphologic and chemical examination of human aortic fibrolipid lesions, which are progenitor lesions for fibrous plaques. The evidence favours a substantial role, perhaps a dominant role, for extracellular lipid accumulation in the formation of the fibrous plaque core region. PMID- 2226526 TI - The role of HDL in reverse cholesterol transport and its disturbances in Tangier disease and HDL deficiency with xanthomas. PMID- 2226528 TI - Initial steps in reverse cholesterol transport: the role of short-lived cholesterol acceptors. AB - The early metabolism of cell-derived cholesterol was followed during the interaction of normolipaemic native plasma with cultured cell monolayers labelled to high specific activity with 3H-cholesterol. Kinetic analysis indicated that initial processing involved several prebeta-migrating high-density lipoprotein (HDL) species. A small prebeta species, the initial acceptor, was first converted to a lipoprotein whose composition predicts a discoidal structure. The free cholesterol content of this was then esterified by lecithin: cholesterol acyltransferase, and its cholesterol converted to the alpha mobility of spheroidal mature HDL the binding of apolipoprotein A-II. These studies follow the genesis of HDL in plasma from peripheral cell membrane cholesterol. PMID- 2226529 TI - Lipoproteins in interstitial fluid of dogs: implications for a role in reverse cholesterol transport. PMID- 2226530 TI - Lipoproteins of human peripheral lymph. AB - The concentration of cholesterol in peripheral lymph is roughly one tenth of that in the blood plasma of the same subject. In lymph, there is virtually no very low density lipoprotein (VLDL), probably due to low permeability of the vascular endothelium for particles of this size. More than 95% of apo B-containing lipoproteins of lymph have the density of plasma low density lipoproteins (LDL). The concentration of apo A-I and apo A-II in lymph is about 15% of that in plasma; yet about 50% of the total mass of both these main HDL apoproteins is present extravascularly. High density lipoproteins (HDL) of lymph appear square packing, and the presence of such large HDL particles is the most conspicuous difference between lipoproteins in plasma and in the extravascular fluids. It remains to be seen whether raising plasma apo A-I concentration per se will increase the initial stages of reverse cholesterol transport and also be clinically beneficial. PMID- 2226531 TI - Atheroma formation: defective control in the intimal round-trip of cholesterol. AB - This article is based on the concluding remarks by the author at the Ninth Paavo Nurmi Symposium on 'Lipoproteins and the Pathobiology of the Arterial Intima'. . . . Circulating cholesterol is carried into the arterial intima, the site of atherogenesis, in low-density lipoprotein (LDL) particles, and from the intima back into the circulation in high-density lipoprotein (HDL) particles. At affected sites in the intima, cholesterol accumulates in deposits known as atheromas. These local accumulations are due to disturbances in the cholesterol flow through the intima, resulting in imbalance between inflow and outflow of cholesterol. The rate of cholesterol accumulation depends ultimately on the severity of the imbalance. The factor primarily responsible for this cholesterol imbalance appears to be local modification of LDL particles. Hence, to prevent accumulation of cholesterol in the intima, the production of modified LDL particles must be prevented. This can best be achieved by reducing the inflow of LDL particles into the intima. This, in turn, can be achieved by lowering the concentration of circulating LDL particles. In addition, increasing the concentration of circulating HDL particles should accelerate the rate of removal of cholesterol from the intima, so further improving the disturbed cholesterol balance at the atheromatous sites. PMID- 2226532 TI - Mapping of proteoglycans in atherosclerotic lesions. AB - The involvement of sulphated glycosaminoglycans in atherosclerotic changes have been studied in human and rat arteries, and biochemical experiments have revealed that a significant increase in the contents of chondroitin sulphate/dermatan sulphate and cholesterol, but loss of heparan sulphate, occurs in human atherosclerotic arterial tissues. Electron micrographs have revealed that extracellular deposits of lipid are predominantly present in areas rich in chondroitin sulphate proteoglycans but not in areas rich in collagen bundles and dermatan sulphate proteoglycans. The different types of proteoglycans have been distinguished in situ by the cuprolinic blue staining method and enzymatic degradation experiments, and their topohistochemical distribution patterns analysed by morphometry of proteoglycan/cuprolinic blue precipitates. The ultracytochemical investigations indicate changes in size and pattern of chondroitin sulphate-rich proteoglycan-cuprolinic blue precipitates in human atherosclerosis. In plaque tissue, these precipitates are significantly enlarged. In addition, they accumulate around smooth muscle cells in the medial tissue. An increase in the size of proteoglycan-cuprolinic blue precipitates has also been observed in balloon catheter-induced lesions in rat carotid arteries. The large chondroitin sulphate as well as the small dermatan sulphate proteoglycan cuprolinic blue precipitates show this alteration 2 weeks after balloon injury. We suggest that quantitative and qualitative alterations in the arterial proteoglycans occur in the pathogenesis of atherosclerosis in addition to the cell proliferation and lipid accumulation. PMID- 2226533 TI - Pathobiology of human familial hypercholesterolaemia and a related animal model, the Watanabe heritable hyperlipidaemic rabbit. AB - Defective expression of low density lipoprotein (LDL) receptors is the basic genetic defect in human familial hypercholesterolaemia (FH) and its animal counterpart, the Watanabe heritable hyperlipidaemic (WHHL) rabbit. The pathologic manifestations of human FH were evaluated based on the study of material from six subjects with homozygous FH and a review of the literature. This analysis indicated that homozygous FH is characterized by accelerated atherosclerosis and prominent lipid accumulation in macrophages and other stromal cells of the aortic and mitral valves, skin, tendon, and, variably, in other extravascular sites. Disease progression was studied in the WHHL rabbit. From birth to 1 year, WHHL rabbits show evidence of progressive disease of the aorta with accumulation of birefringent lipid in intimal lesions, including fatty streaks, raised foam cell lesions, and plaques (atheromas), as well as in the media. At 1-2 years, WHHL rabbits develop coronary atherosclerosis and focal extravascular lipid deposits, including subcutaneous and tendinous xanthomas. Vascular lesion development is associated with adhesion of monocytes and other leucocytes to the endothelium. The cells of the intimal lesions are lipid-containing macrophages, smooth muscle cells and foam cells. Most of the intracellular lipid is in the form of non membrane-bound neutral lipid droplets indicating that the cytoplasm is the major site of lipid storage. Similar ultrastructural features are shown by human FH lesions. Observations are reviewed regarding therapeutic approaches aimed at altering the pathologic expression of familial hypercholesterolaemia, including the negative results of treatment of WHHL rabbits with the calcium-channel antagonist, verapamil, and omega-3 fatty acids. PMID- 2226534 TI - Intimal thickening in the coronary arteries of infants and children as an indicator of risk factors for coronary heart disease. AB - Narrowings of the coronary arteries were measured in 94 infants aged less than 1 year who died in hospital and 102 1- to 16-year-old children who died accidentally. The arteries were transformed mathematically to circles. The degree of narrowing caused by intimal thickening was determined as the ratio of intimal area to the original luminal area. This ratio was further transformed to percentage. The degree of narrowing varied between 0 and 58% (mean 20%). The mean degree of narrowing in the left coronary artery during the first year of life was 17% and, between 12 and 15 years, 34%. Narrowing was greater in males (P = 0.02), when all the 333 coronary samples were included in the analysis. The birthplaces of the subjects' grandparents were traced from population registers and it was found that narrowing in the left coronary artery of infants was greater in those descended from grandparents from eastern Finland, an area of high mortality from coronary heart disease (CHD). Intimal thickening in infants and children seems to be a morphological manifestation of hereditary predisposition to CHD. PMID- 2226535 TI - Transport of low density lipoproteins across endothelial monolayers. PMID- 2226536 TI - Transport, interactions and retention of plasma proteins in the intima: the barrier function of the internal elastic lamina. AB - This paper presents a brief overview of our current understanding of the relation between plasma macromolecules and atherogenesis. Plasma proteins enter normal intima by vesicular transport across normal endothelium, and convective transport within the intima; accumulation depends mainly on molecular size and the molecular sieve properties of the internal elastic lamina. Within the intima the proteins may be modified; particularly striking changes occur in high density lipoprotein (HDL) and in fibrinogen. Fibrinogen appears to be converted to fibrin which is then lysed, providing a continuing source of fibrin degradation products (FDP). Fibrin also seems to be associated with a tightly bound, plasmin releasable apo-B-containing lipoprotein; work in progress suggests that much of this fraction is accounted for by lipoprotein(a). PMID- 2226537 TI - Lipoproteins in normal and atherosclerotic aorta. AB - Each method used for the extraction and isolation of intimal lipoproteins has advantages and disadvantages. Gentle extraction methods are needed to characterize subtle modifications in the structure and biologic properties of the lipoproteins, whereas more aggressive methods are needed if the goal is to maximize the yield of lipoproteins from atherosclerotic arteries. The present paper evaluates different methods used for the isolation of intimal lipoproteins. Normal intima contains remnant-like and low density lipoprotein (LDL)-like particles that more strongly stimulate cholesterol esterification in macrophages than do control plasma LDL. Both fractions contain apolipoprotein (apo) E but neither shows clear signs of oxidative modification. LDL-like particles from atherosclerotic lesions, on the other hand, contain malondialdehyde- and 4 hydroxynonenal-lysine adducts in apo B, are chemotactic for monocytes and show increased degradation in macrophages, a process that oxidized LDL prepared in vitro can compete with. The findings support the conclusion that at least a portion of the LDL isolated from atherosclerotic lesions is similar, if not identical, to oxidatively modified LDL. PMID- 2226538 TI - Controversial indications. Rationale for thrombolysis: later than 4-6 h from symptom onset, and in patients with smaller myocardial infarctions. The ISAM Study Group. AB - To evaluate the effect of late reperfusion of an infarct-related coronary artery on left ventricular (LV) function in the month after myocardial infarction (MI), findings from 386 patients in the Intravenous Streptokinase in Acute Myocardial Infarction (ISAM) trial were studied. All patients had a late peaking in the creatine kinase-MB serum time-activity curve, suggesting absence of early reperfusion. Significantly better LV function associated with patency of the infarct artery at angiography 1 month after the acute event confirmed the beneficial effect of reperfusion even if achieved beyond the time window for myocardial salvage. Thrombolysis commenced later than 4-6 h after symptom onset will be of benefit as long at it reopens infarct arteries more often and earlier than occurs spontaneously or from anticoagulation. The value of the size of the sum of ST-segment elevation (sigma ST increases) on admission ECG was evaluated from the total ISAM study population. The relation between sigma ST increases and final infarct size as well as mortality risk was highly significant. However, weak correlations largely limit the value of sigma ST increases to predict the outcome in an individual patient. Thus, whatever the relative beneficial effect in patients with smaller or larger MI may be, it would be unwarranted to withhold thrombolytic therapy from patients with smaller sigma ST increases on admission ECG. PMID- 2226539 TI - Thrombolysis: adjuvant therapy and the role of complement. AB - A possible role for adjuvant therapy following thrombolysis exists in the context of reperfusion injury and post-ischaemic dysfunction, or so-called 'stunned myocardium'. The question that arises is whether the extent of myocardial stunning, or the ultimate extent of necrosis, can be reduced by preventing reperfusion injury and the impairment of reflow. Essential to any attempted intervention is an understanding of the mechanisms underlying myocardial damage following ischaemia and reperfusion. Certain mediators responsible for injury and repair have been identified, and their effects modified in experimental preparations; the role of complement, in particular, is central to these phenomena. Lysis of coronary artery thrombus is only the initiator of a sequence of events involving vascular endothelium and an intravascular response to tissue injury. The challenge is whether reperfusion injury may be modified and whether such intervention will favourably alter clinical outcome. PMID- 2226540 TI - Pre-hospital thrombolysis, is it useful? AB - Thrombolytic treatment efficacy is greater when the delay between onset of pain and treatment is short. One way to shorten this delay is to give treatment at home, but one cannot recommend this technique if it has not been demonstrated first, that pre-hospital thrombolysis is feasible and safe, and second, that it is useful. We have been able to demonstrate that pre-hospital thrombolysis with APSAC is feasible and safe. Our findings are similar to those of other teams using other drugs. Whether pre-hospital thrombolysis is useful has not been adequately assessed; and we consider that first, the benefit of pre-hospital vs in-hospital thrombolysis must be determined, and second, the results of a study involving many centres, with various levels of training, practicing pre-hospital thrombolysis must be examined. Two large scale studies are currently being performed. One in Seattle, uses left ventricular ejection fraction as the major end-point, whereas the other, the European Myocardial Infarction Project, (EMIP) is using total mortality. Data currently available indicate that pre-hospital thrombolysis with APSAC is feasible, easy and safe. We hope that we will very soon be able to answer the last question: is it useful? PMID- 2226542 TI - Time as a factor in thrombolytic therapy. AB - There is abundant evidence from angiographic studies that reperfusion and/or patency rates are greater when thrombolysis is initiated earlier. Evidence of a reduction in infarct size has been provided by a number of studies, which have also suggested that earlier therapy preserves left ventricular function. The major intravenous thrombolytic mortality trials appear to confirm the importance of delivering therapy soon after the onset of symptoms e.g. GISSI and ISIS-2. However, the benefit reported in the first hour in GISSI may be questioned. Furthermore, it seems probable that those coming in late to trials are patients who did not have a sudden onset of symptoms, but whose symptoms persisted, perhaps with recurrent pain, or with heart failure symptoms. This may account for the fact that the benefit seen relatively late, particularly in ISIS-2, does not seem to accord with reperfusion, infarct size and LVEF findings. The true benefits of earlier therapy will be established only when patients are randomized to active therapy or placebo at one point in time and then switched to alternative therapy at a specified later time. This has been done in a small trial with alteplase in Belfast. The findings were suggestive but not conclusive of an improvement in LVEF in those treated earlier. The European Myocardial Infarction Project (EMIP) should go far towards answering the question. In most European cities the time between onset of symptoms and the initiation of skilled treatment for myocardial infarction is of the order of 5-6 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226541 TI - Reduction in hospital time to thrombolytic therapy by audit of policy guidelines. AB - Despite the importance of early thrombolysis in the treatment of acute myocardial infarction, unacceptable delays in drug administration still occur in hospital. From March 1989 we decided to monitor our performance, and thereby to reduce avoidable in-hospital delay to a minimum. Potential candidates for thrombolytic therapy were identified by paramedic ambulancemen whenever this was feasible. Rapid check-lists were used for inclusion and exclusion criteria in the Accident and Emergency Department. A target of 15 min was set for time to treatment, and reasons for any gross deviation (greater than 30 min) were explored in each instance. As a result of these strategies, we achieved a median time from admission to initiation of thrombolysis in 50 consecutive patients of 17 min. The 39 patients treated with injections of APSAC as opposed to infusions of streptokinase had a median in-hospital delay to treatment of only 13 min. PMID- 2226543 TI - The role of intervention following thrombolysis for acute myocardial infarction. PMID- 2226545 TI - Birth weight of children with congenital heart disease. AB - Birth weights of 843 children with congenital heart disease (CHD) were compared to the respective data of a normal West German population. On average, the CHD group had significantly lower birth weights, but the weight deficit was far less pronounced than in previous studies. The decrease in birth weight was distinct only in children with tetralogy of Fallot and atrial septal defect. Compared to normal newborns, patients with CHD were more often small for gestational age (15.0%) or had a low (less than 2500 g) birth weight (8.6%). The prevalence of prematurity was not increased. Extracardiac malformations were not significantly more common in CHD patients, who were small for gestational age, than in CHD patients with normal birth weight. PMID- 2226546 TI - Diagnosis, therapy, and outcome of ventricular septal defects in the 1st year of life: a two-dimensional colour-Doppler echocardiography study. AB - Between January 1987 and July 1989 a ventricular septal defect (VSD) as a single cardiac lesion was detected in 269 small infants aged less than 1 year. The diagnosis was achieved by two-dimensional echocardiography and Doppler colour flow mapping using subcostal, parasternal, apical, and suprasternal views. VSDs were divided into perimembraneous, muscular, malalignment, and subpulmonary defects. Septal defects in complex lesions and atrioventricular defects were excluded. In group 1 (174 infants up to 4 weeks of age, mean 10 days) 125 muscular (71.8%), 35 (20.1%) perimembraneous, 12 (6.9%) malalignment, and 2 (1.1%) subpulmonary defects were diagnosed. One baby had a combined perimembraneous and muscular defect. In another baby a malalignment defect was associated with an av-canal. In group 2 (95 infants aged 4 weeks to 1 year, mean 4.0 months), 57 (60%) muscular, 32 (33.6%) perimembraneous and 6 (6.3%) malalignment defects were found. Within the maximum observation period of 13 months, spontaneous closure occurred in 72 (42.6%) of 169 infants who had a sufficient follow up. Sixty-four had a muscular (88.9%) and 8 (11.1%) a perimembraneous defect. Surgical intervention was required in 11 patients: five perimembraneous defects were closed, one was palliated. Five infants with a malalignment defect were palliated. The malalignment defect frequently needed surgical intervention even in newborns; it never closed spontaneously. About 10% of patients with perimembraneous septal defect required surgery. Spontaneous closure rarely occurred in early infancy. Muscular VSDs were most frequent but virtually never required therapy. Spontaneous closure rate was about 50% during the 1st year of life. PMID- 2226544 TI - Cystic fibrosis, pathophysiological and clinical aspects. AB - Cystic fibrosis is a lethal, hereditary, until recently little understood disease, which leads to progressive functional disturbances in various organs, including the lungs, liver and pancreas. Knowledge of the genetic and cellular abnormalities is rapidly progressing, but therapy is still symptomatic and based on insufficiently controlled and short-term studies. At present the therapeutic approach aims to combat respiratory infections by optimal antibiotic therapy, combined with techniques to promote sputum evacuation. Additional measures attempt to optimise both nutritional state and physical condition. Median survival has improved from approximately 1 year to about 25 years during the past 3 decades. This article summarises present information on disease mechanisms and treatment. PMID- 2226547 TI - A new device to measure short-term growth of head circumference in newborn infants. AB - We have developed and tested a new instrument to measure the occipitofrontal head circumference of newborn infants more accurately. The intra- and interobserver variability was determined. The results indicate that the head circumference of newborn infants can be measured with an accuracy of 1 mm. PMID- 2226548 TI - Maximal steady state blood lactate levels in 11-year-old boys. AB - To evaluate whether anaerobic threshold criteria evaluated in adults are pertinent to children, ten boys with a mean age of 11.2 years were investigated during treadmill running. Maximal running velocity was determined at stepwise increasing load, with determination of blood lactate following exercise. On the following days four runs each lasting 16 min were performed at a constant speed starting with a speed corresponding to about 70% of the maximal speed and increasing it during the next run in order to determine maximal steady state levels of blood lactate. Blood lactate was measured at the end of every 4 min period. From this date the anaerobic threshold was calculated. The correlation between anaerobic threshold values and maximal steady state levels of blood lactate was poor, however, a steady state of blood lactate was present at 4.6 mmol/l, whereas the mean anaerobic threshold value was determined at 2.6 mmol/l. In view of our results, the anaerobic threshold during increasing work does not correspond to the true anaerobic threshold, which can be assumed to occur at much higher lactate values. The meaning of the term anaerobic threshold is therefore to be questioned. PMID- 2226549 TI - Protein C activity and antigen levels in childhood. AB - Hereditary protein C deficiency is an important risk factor for thrombosis. To enable its diagnosis shortly after birth, we determined reference values of protein C antigen and activity levels for the first 3 months of life. To establish an age-related range of protein C levels we also determined median values for individuals up to 18 years of age. A good correlation between the two levels was seen from the 3rd/4th month of life onwards, whereas in the first 2 months the activity levels were significantly lower than the antigen levels. This was not due to interference by the increased plasma citrate concentration at high haematocrit values, and may suggest a dysfunctional protein C molecule in the neonatal period. We found a rapid rise in protein C activity and antigen levels until the age of 7-9 months, followed by a slower progression toward adolescence. In contrast to previous reports, our results indicate that adult values are probably not achieved until sometime during the 2nd decade of life. PMID- 2226550 TI - Intravenous immunoglobulin in Diamond-Blackfan anaemia. AB - Since immunological disorders have been demonstrated in patients with Diamond Blackfan anaemia (DBA), intravenous immunoglobulins (IVIG) were administered to a 14-year-old girl with DBA and congenital malformations, previously treated with corticosteroids and blood transfusions. No therapeutic effect was observed. PMID- 2226551 TI - Simultaneous palsy of facial and vestibular nerve in a child with Lyme borreliosis. AB - We describe a boy with borreliosis characterized by lymphocytic meningitis and simultaneous palsy of facial and vestibular nerves on the left side. A mild sensoneural affection was also confirmed by brainstem evoked response audiometry. While symptoms of vestibular dysfunction quickly decreased during antibiotic treatment, facial palsy improved only slowly. PMID- 2226552 TI - A patient with features of both Bardet-Biedl and Alstrom syndromes. AB - We describe a 30-year-old patient with acanthosis nigricans, diabetes mellitus with insulin resistance, hypogonadotropic hypogonadism, pigmentary degeneration of the retina and cerebellar, pyramidal and posterior columnar involvement. He had normal mental function, normal hearing and no hexadactyly. The patient had symptoms of both Bardet-Biedl and Alstrom syndromes, but did not manifest all the main features of either syndrome. This suggests either that the Bardet-Biedl, Alstrom, Laurence-Moon syndromes (including the variant described by Edwards) have a highly variable expression or that our case is a new variant within this group of syndromes. PMID- 2226553 TI - Thoraco-abdominal enteric duplication with meningocele, skeletal anomalies and dextrocardia. AB - We describe an infant with an enteric thoraco-abdominal duplication arising in the proximal jejunum and associated with a dorsal meningocele, dextrocardia, agenesis of ribs and hypoplasia of the left arm. Diagnosis was reached post operatively and the infant died of cytomegalovirus pneumonitis. Results of the postmortem examination are presented. Awareness of this rare malformation is required in order to reach a timely diagnosis and to plan a suitable operative approach. PMID- 2226554 TI - Variation of alpha 1-antitrypsin glycoprotein microheterogeneity in hepatic postresuscitation disease. AB - Microheterogeneity of the glycoprotein alpha 1-antitrypsin has been investigated sequentially by high resolution isoelectric focusing in a child with the proteinase inhibitor MS phenotype after near-drowning. A band-splitting with additional cathodal fractions exhibited migration from the most cathodic to the anodic positions of the glycoprotein isoforms in the course of post-resuscitation disease. The pattern may reflect the time- and stage-dependent hypoxic and post hypoxic effects on hepatocellular metabolic zonation. PMID- 2226555 TI - The use of metronidazole in management of methylmalonic and propionic acidaemias. AB - Gut bacteria have been implicated as an important source of propionate in children with inborn errors of propionate metabolism. We have investigated the value of oral metronidazole (10-20 mg/kg per day) in five children with methylmalonic acidaemia (MMA) and four with propionic acidaemia (PA). Urinary excretion of propionate metabolites fell significantly during the treatment in all subjects, the mean decrease being 41% (range 12-76, P less than 0.01), while mean plasma propionate was reduced from 45.0 mumol/l to 25.1 mumol/l (P less than 0.05). Substantial reduction of the gut bacterial population was confirmed by lactulose breath hydrogen tests and by stool culture, and stool propionate concentration was reduced in most subjects. Clinical improvement was noted in three children. These results suggest that long-term antimicrobial therapy may offer significant clinical benefit to children with inborn errors of propionate metabolism. PMID- 2226556 TI - Routine lumbar punctures in the newborn--are they justified? AB - The records of 62,107 neonates cared for at three neonatal referral units between 1979 and 1985 were analysed with regard to the number of lumbar punctures (LP) performed and the results obtained. The mean perinatal mortality rate was 9.3/1000 live births and the neonatal mortality rate was 5.9/1000. The units were comparible in this respect. Two hundred and sixty three (0.4%) babies weighed less than 1.0 kg at birth and 510 (0.8%) babies weighed 1.0-1.5 kg. A total of 1554 LPs were performed on 1084 babies, 1.7% of the whole population. Seventeen babies were diagnosed as having meningitis following CSF examination; 5 weighed less than 1.5 kg (VLBW) (incidence of meningitis 6.5/1000 births) and 12 weighed more than 1.5 kg (incidence 0.2/1000 live births). An LP was performed on 44% of VLBW babies and 1.2% of babies weighing more than 1.5 kg. In both groups approximately 1.5% of CSF samples were positive. Eight of the 17 positive results were obtained during the first 3 postnatal days. Only one VLBW baby had meningitis on the 1st day of life (1.3/1000). In view of the low incidence of meningitis and the risk factors associated with an LP it is questionable whether this procedure should be a routine investigation in the VLBW newborn. PMID- 2226557 TI - Relationship between mode of delivery and neonatal calcium homeostasis. AB - Serum levels of calcium (Ca), calcitonin (CT) and parathyroid hormone (PTH) were determined in cord blood of 229 newborns. In 136 newborns the tests were repeated 24 h later. The probands were divided into four groups according to mode of delivery: (1) spontaneous; (2) elective caesarean section without labour; (3) elective caesarean section in labour; (4) emergency caesarean section with fetal distress. Newborns in group 2 had significantly lower Ca and CT levels and significantly higher PTH concentrations in cord blood than the other three groups. In all groups Ca and PTH concentrations were negatively correlated. At 24 h, mean Ca levels had decreased and mean CT and PTH concentrations had increased in all four groups. Newborns in group 2 still had lower Ca levels but higher CT and PTH concentrations. At that time there were negative correlations between Ca and CT levels in groups 1 and 2 and between Ca and PTH concentrations in group 1. These data demonstrate that without labour, cord blood Ca and CT levels are lower and PTH concentrations are higher. The low 24 h calcium in newborns delivered without labour is explained by the lower Ca levels at birth and a tremendous increase of CT. The PTH secretion in full-term newborns is very substantial and negatively correlated with Ca levels. PMID- 2226558 TI - Neonatal hepatic haemangioendothelioma: presentation with jaundice and microangiopathic haemolytic anaemia. AB - A neonate with multicentric hepatic haemangioendothelioma complicated by jaundice and microangiopathic haemolytic anaemia is presented. To our knowledge such a constellation has not been previously reported. PMID- 2226560 TI - VACTERL-association: an unusual case of fetus detected by ultrasound screening at 19 weeks of gestation. PMID- 2226559 TI - Biochemical evidence for the need of long-term mineral supplementation in an extremely low birth weight infant fed own mother's milk exclusively during the first 6 months of life. AB - In an extremely low birth weight infant fed expressed own mother's milk exclusively during the first 6 months of life, introduction of a human milk fortifier resulted in improvement of biochemical alterations consistent with metabolic bone disease of prematurity. Attempts to discontinue fortification at 9 weeks (discharge) and 21 weeks of age induced deterioration of biochemical parameters, demonstrating a persistent need for mineral supplementation during the whole period of breast-feeding. The effects of long-term human milk fortification are discussed. PMID- 2226561 TI - Transfontanellar ultrasonography in HIV-positive children. PMID- 2226562 TI - Varicella-associated pancytopenia. PMID- 2226563 TI - Immunization against cow's milk in infants with cleft lip and/or palate. PMID- 2226565 TI - Thoughts of a reviewer. PMID- 2226564 TI - Childhood Lyme borreliosis in Europe. AB - Lyme borreliosis is a multisystem disorder common in childhood. It is an acute and persistent anthropozoonotic infection caused by the spirochete Borrelia burgdorferi (Bb) which is transmitted by Ixodes ticks. After the tick bite in summer, erythema migrans, meningoradiculoneuritis, or carditis may develop within the same season. Later manifestations may be oligo-arthritis, progressive encephalomyelitis, or acrodermatitis chronica atrophicans. The most common course is probably asymptomatic. Connatal infection is possible. Diagnosis is established mainly by history and clinical manifestations. The antibody response to Bb can be measured in serum and cerebrospinal fluid. Tests may be false negative early in the course of the disease or after early treatment. False positive results may be caused by cross-reactions. Interpretation of test results must also consider unrelated anamnestic titres or asymptomatic infection. Treatment with appropriate antibiotics cures the disease in most patients, however some patients may not respond. The optimal drug has not yet been found. Best prophylaxis is by early removal of the tick from the skin. PMID- 2226566 TI - Growth and endocrine disorders in optic glioma. AB - Hypothalamo-pituitary function in children with optic glioma may be impaired by the tumour itself and by the high cranial radiation doses used in treatment. This study evaluates the effect of optic glioma and its treatment on patient growth and pubertal development. Twenty-one patients (13 boys, 8 girls), treated for optic glioma by cranial irradiation (45-55 Grays) at a mean age of 5.4 years, were evaluated before (n = 10) and/or after (n = 21) irradiation. Growth hormone (GH) deficiency was present in only 1 patient tested before irradiation and in all patients after irradiation. Precocious puberty occurred in 7/21 cases, before irradiation in 5 patients and after irradiation in 2 patients. The cumulative height loss during the 2 years after irradiation was 0.2 +/- 0.2 SD (m +/- SEM) in 7 patients with precocious puberty and 1.1 +/- 0.2 SD in 14 prepubertal patients (P less than 0.01). The corresponding bone age advance over chronological age, evaluated 1-3 years after irradiation, was 1.1 +/- 0.5 and 0.7 +/- 0.3 year in the two groups (P less than 0.01). The mean height loss between time of irradiation and the final height was 2.3 +/- 0.6 SD (n = 6). Primary amenorrhoea, associated with low oestradiol levels, occurred in two of the three girls of pubertal age. These data indicate that the high dose of cranial radiation used to treat optic glioma invariably results in GH deficiency within 2 years and that hGH therapy is required when GH deficiency is documented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226567 TI - Cellular cytotoxicity against autologous hepatocytes in children with different forms of chronic hepatitis B. AB - Cell-mediated immune reactions play the most important role in the pathogenesis of chronic viral and auto-immune hepatitis. Cellular cytotoxicity (CC) of peripheral blood lymphocytes against autologous hepatocytes isolated from liver biopsies was studied in 29 children with different types of hepatitis B surface antigen (HBsAg)-positive hepatitis. Children with chronic hepatitis B showed higher cytotoxicity than control patients. However, a correlation of cytotoxicity to serum amino-transferases, HBeAg-/Anti-HBe-status, and hepatitis B virus DNA in serum could not be found. Children with a higher percentage of hepatitis B core antigen (HBcAg) expression in their liver tissue presented lower CC values, and vice versa. This supports the hypothesis that virus elimination occurs via T-cell attack against HBcAg expressing hepatocytes. Furthermore, children with a longer duration of chronic hepatitis B had considerably higher cytotoxicity values. Possibly, CC plays a role in perpetuating liver damage after infection with hepatitis B virus. PMID- 2226568 TI - Neurological outcome in high risk weight appropriate for gestational age preterm children at early school age. AB - Neurological development in preterm children with birth weight appropriate for gestational age is reported in two separate groups: a longitudinal study of 97 preterm children and 93 term children as a control group and a cross-sectional study of 249 preterm children. Both preterm groups were regarded as high risk with respect to number of outborns, distribution of gestational age and perinatal risk factors. Neurological outcome at 5-6 years of age in the majority of the preterm children was comparable to that of the term children. However, 15% of boys and 9% of girls in the preterm group were diagnosed as having cerebral palsy. Mild diplegia was most frequently observed; 4% of the children were severely impaired. Fourteen percent of the preterm vs 2% of the term boys and 6 9% of the preterm vs none of the term girls received motor therapy during early school age. There was a small but consistent sex difference in neurological outcome in favour of the term and preterm girls. Effects of drop out rate and of incompleteness of ascertainment are reported in detail. PMID- 2226569 TI - Intellectual outcome, speech and school performance in high risk preterm children with birth weight appropriate for gestational age. AB - Intellectual development, speech and school performance of preterm infants with birth weight appropriate for gestational age are reported in two separate investigations: a longitudinal study of 97 preterm children and 93 term children as a control group, and a cross-sectional study of 249 preterm children. Both preterm groups were regarded as high risk groups with respect to number of outborns, distribution of gestational age and perinatal risk factors. Intellectual outcome at 5 and 7 years of age in the majority of the preterm children was comparable to that of the term children. However, 8% of the preterm boys and 2% of the preterm girls achieved lower IQ scores than any of the term children. Between 15% and 17% of the preterm boys and 9%-12% of the preterm girls did not attend school at grade level, compared to 4% and 2% in the term group, respectively. Intellectual and neurological development and school performance were higher interrelated in the preterm than in the term children. Articulation defects, stuttering and dysgrammatism occurred more frequently in the preterm than in the term children and in boys more so than in girls. PMID- 2226570 TI - Pulse oximetry used for documenting oxygen saturation and right-to-left shunting immediately after birth. AB - The objective of this study was to investigate the clinical applicability of pulse oximetry to measure haemoglobin oxygen saturation and heart rate in the first 20 min of life and to analyse the effect of pre- or post-ductal (hand, respectively, foot) fixation of sensors on oxygen saturation. Measurements were carried out on 53 newborn infants selected at random after delivery by caesarean section. Signal detection occurred significantly faster from the hand (50% after 1.3 min, 90% after 4 min) than from the foot (50% after 3.1 min, 90% after 9 min). Both fixation sites showed equally great sensitivity to motion. The heart rates from pulse oximetry recordings were up to 30% lower than those from ECG recordings. Saturation values from the hand were nearly always higher than those from the foot (median difference in the 5th min was 10%; between the 5th and 10th min it was 7%; no significant difference occurred after the 17th min). We conclude that pulse oximetry can be used for documenting oxygenation and right-to left shunting in newborn infants during the first minutes of life in spite of limitations due to incomplete pulse wave detection and artifacts. PMID- 2226571 TI - Cardiomyopathy and multicore myopathy with accumulation of intermediate filaments. AB - A girl affected by a restrictive cardiomyopathy with neuromuscular involvement is described. Morphological examination showed a pattern of multicore myopathy and with electron microscopy a sarcoplasmic accumulation of electron dense granular and filamentous material was demonstrated both in skeletal muscle and heart. This peculiar electron dense material corresponded to increased desmin in muscle and cardiac fibres and was demonstrated immunohistochemically. PMID- 2226572 TI - Fluctuation in the concentrations of vanillylmandelic acid and homovanillic acid in mass screening for neuroblastoma. AB - Fluctuations in the amount of vanillylmandelic acid (VMA) and homovanillic acid (HVA) were studied in random urine samples from 13 infants with neuroblastoma. In patients with a small tumour, many samples contained amounts below the cut off values, suggesting that detection of a patient with neuroblastoma depended on mathematical probability. Using high performance liquid chromatography a patient with a tumour of about 10 g may well be overlooked, whereas a patient whose tumour weighs over 30 g would probably be detected. With qualitative screening, although more likely to miss a patient with low VMA excretion, a patient with a tumour weighing over 50 g would be detected. In a thorough hospital examination care should be exercised in interpreting borderline values of VMA and HVA; excretion information suggesting the existence of a tumour may aid localization by radiological imaging procedures. PMID- 2226573 TI - Lung volumes following resection of pulmonary metastases in paediatric patients- a retrospective study. AB - Pulmonary function was evaluated before and after 15 operations for resection of pulmonary metastases from osteogenic sarcoma. In the whole study group (ten patients, aged 13-18 years) preoperative vital capacity (VC) ranged from 62% to 122% (mean 83%) of predicted normal values for height. The operations were performed via median sternotomy. One-28 metastases were removed per session. Six months after the operations VC averaged nearly 95% of the preoperative values. Signs of bronchial obstruction or persistent pulmonary hyperinflation were only present in one patient with repeated operations. We conclude that resection of pulmonary metastases with limited loss of parenchyma leads to an almost complete recovery of preoperative pulmonary function parameters. PMID- 2226574 TI - Pelvic lipomatosis in the Proteus syndrome: a further diagnostic sign. PMID- 2226575 TI - Clinical implications of cartilage metabolism in arthritis. AB - The ability of articular cartilage to withstand repeated mechanical loading with relatively little wear over a lifetime results from the properties of the extracellular matrix (ECM) and the optimal function of the chondrocytes which are responsible for the synthesis and presumably maintenance of this ECM. The properties of the ECM are accounted for by the relationship of the major aggregating, polyanionic, negatively charged proteoglycans with their potent viscoelastic properties to the network of collagens and several noncollagenous proteins. The major collagen (type II) interacts with type IX collagen in a highly specific manner. Type IX collagen has a chondroitin sulfate side chain and can also bind to the aggregating proteoglycans through a basic amino terminal domain. In inflammation, injury and probably repeated wear, function of the chondrocytes is disturbed, mediated by the action of potent cytokines, which results in release of degradative enzymes and alterations in the pattern of synthesis of the ECM. Identification of the critical cytokines and the sequence of events that result from their action should provide the basis for rational prophylaxis and therapy of disorders such as osteoarthritis and rheumatoid arthritis. Articular cartilage has unique mechanical properties which permit repeated mechanical loading with relatively little wear over a lifetime. These properties result from the special character of the extracellular matrix (ECM) and optimal functioning of the component cells (chondrocytes) which are responsible for the synthesis and presumably, maintenance of this matrix. Articular chondrocytes survive and perform these critical functions in an anaerobic environment remote from the vasculature and must derive their nutrition from the synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226577 TI - Symposium on cell movement. Belgian and Dutch Societies for Cell Biology. Antwerpen, 22-23, November 1990. Abstracts. PMID- 2226576 TI - Annual meeting of the Dutch Society for Cell Biology, Nijmegen. 29-30 January 1990. Abstracts. PMID- 2226578 TI - 'Solitary' Ta-T1 G1 bladder tumour--history and long-term prognosis. AB - Natural history of 'solitary', histological grade 1, stage Ta-T1 transitional cell carcinoma of the bladder was studied in 198 patients retrospectively over a period from 1975 to 1987. Three patterns of tumour behaviour were evident. In 56% of patients the tumour did not recur following the initial resection. Twenty-one percent developed recurrences localised to the site of the original tumour. This group became tumour-free by 5 years and remained so thereafter. The remaining 23% continued to produce recurrent tumours up to 10 years at different sites in the bladder. The actuarial percentage of patients who remained continuously free of tumour after the initial resection was 53% at 5 years and 51% at 10 years. The results of this study suggest that cytoscopic follow-up may be discontinued in patients who remain continuously tumour-free for 5 years. PMID- 2226579 TI - External-beam radiation for carcinoma of the prostate. AB - Over 14 years 111 patients with prostatic cancer underwent attempted curative radiotherapy; full data was obtained on 105 patients. The 5-year actuarial survival rate was 62%, with 54 patients still alive at the time of review. The toxicity rate was 94%, and serious late complications occurred in 4%. 40% of the patients developed symptomatic recurrence, and only 4% of the patients had local recurrence. PMID- 2226580 TI - Maximal electrical stimulation in the treatment of unstable detrusor and urge incontinence. AB - Ninety-one patients with unstable detrusor and urge incontinence were treated with maximal electrical stimulation. There were 17 dropouts. From the remaining 74 patients 51 were subjectively cured or significantly improved, this effect lasted for more than 6 weeks in 40. Objectively a significant decrease in frequency was found, also a significant increase in bladder volume. No effect on detrusor pressure at bladder contraction was noted. PMID- 2226581 TI - The role of abdominal and transrectal ultrasound and cytology in the detection of recurrent bladder tumours. AB - Transrectal and transabdominal ultrasound combined with cytology were compared with conventional cystoscopy as a mean of detecting recurrences of bladder tumours. One hundred and twenty-five patients underwent combination ultrasound in the outpatient department 1 week before cystoscopy. Combination ultrasound identified 90% of recurrent tumours and tumour identification with the results of ultrasound and cytology combined was 93%. The false positive rate was 2%. The ultrasonographer would have referred 97% of patients with recurrent tumour for cystoscopy. Combination ultrasound and cytology may be a satisfactory alternative to check cystoscopy in certain categories of bladder tumours. PMID- 2226582 TI - Comparison of the incidence of Ureaplasma urealyticum in infertile men and in donors of semen. AB - 569 infertile patients and 75 fertile men (donors of semen) were included in our study from 1985 to 1987. We compared the frequency of Ureaplasma urealyticum in semen specimens in these two groups: 40 infertile men (7%) and 4 donors of semen (5.3%) had U. urealyticum in semen cultures. This difference was not statistically significant. We concluded that U. urealyticum was not more frequent in infertile than in fertile men. We also report the results of semen cultures for other bacteria and the parameters of routine semen analysis in these two groups. All infertile patients infected by U. urealyticum were treated with doxycycline: the infection was eradicated in 77.5% of them. PMID- 2226583 TI - Quantitative analysis of trace elements in human clear cell carcinoma of the kidney by energy-dispersive X-ray fluorescence. AB - In a case-control study, 20 cases of renal cell carcinoma (RCC) were analyzed by energy-dispersive X-ray fluorescence in order to establish the concentration of Fe, Cu, Zn and Cd. Patients with RCC were examined and compared with 7 controls from selected autopsies. A significant decrease in Cd and Zn concentration was found in the neoplastic tissue in all cases. In contrast, no significant decrease in Cu concentration was detected in our cases. PMID- 2226584 TI - Flow cytometry analysis of urothelial cell DNA content according to pathological and clinical data on 100 bladder tumors. AB - DNA content of 100 bladder tumors (34 grade I, 42 grade II and 24 grade III, WHO classification) were studied by flow cytometry. Ten normal bladder samples were used as control. The 100 bladder tumors could then be separated into two groups. A first group of 60 tumors (60%) had a unimodal distribution with a diploid peak and a DNA index close to 1.0, 32 grade I, 22 grade II and 6 grade III tumors displayed this pattern as did the 10 normal bladders. The second group (40%) had a bimodal distribution with two peaks, the first one (diploid peak) with a DNA index of 1.0, the second (aneuploid peak) with a DNA index greater than 1.0. Two grade I, 20 grade II and 18 grade III tumors belonged to this group. Frequency of the aneuploid peak increased with tumor grade and infiltration progression. Hence 6% of grade I, 48% of grade II and 75% of grade III tumors showed an aneuploid peak as well as 8% of Pa, 46% of P1, 73% of P2 and 87.5% of P3 stage tumors. This study showed that a good correlation exists between flow-cytometric, pathological and clinical data. PMID- 2226585 TI - Leiomyosarcoma of the renal vein: a report of two cases. AB - We report 2 cases of leiomyosarcoma of the renal vein. The diagnosis, assessment, treatment and prognosis of this uncommon tumour are discussed with reference to 15 other cases reported in the literature. PMID- 2226586 TI - Carcinoma of the penis in lichen sclerosus atrophicus. A case report. AB - Three cases of glans penis epidermoid carcinoma after lichen sclerosus et atrophicus (LSA) or balanitis xerotica obliterans are discussed. Relationships between both diseases are analyzed but remain unclear. Balanitis xerotica obliterans causes foreskin and urethral meatus stenosis that requires circumcision. Glans penis carcinoma can be observed many years later even after circumcision. The knowledge of LSA is important to do circumcision at the beginning of the disease with a long-term follow-up of these patients to realize a glans penis biopsy if necessary. Most cases of LSA are not recognized, and the frequency is higher than reported. PMID- 2226587 TI - Early 'invasive' malignant melanoma of the glans penis and the male urethra. Report of a case and review of the literature. AB - A 40-year-old male with early 'invasive' malignant melanoma of the glans penis and meatus urethrae externus is presented. Early stages of primary melanoma of the glans penis and the male urethra are distinctly rare and are often clinically indistinguishable from penile lentigo, melanosis and melanocytic nevus on the genitalia. In order to avoid large and useless surgery on such a delicate location we propose a punch biopsy with subsequent histological examination prior to definitive surgical procedure. Whereas malignant melanoma of the penis with a thick Breslow index is treated with extended surgical management, only local excision of the tumor without groin dissection was performed in our patient. PMID- 2226588 TI - Use of Biopty gun for corpus cavernosum biopsies. AB - Needle biopsy of the corpus cavernosum with the Biopty gun system has been performed in impotent patients. This technique is cost-effective, rapid, safe, relatively harmless and effective in obtaining erectile tissue to identify the presence of intracavernous structures (smooth muscle cells, collagen, arteries and nerves). It can certainly replace the open method, but we have to determine its place in the assessment of impotent patients. PMID- 2226589 TI - Results after organ-preserving surgery for renal cell carcinoma. An Austrian multicenter study. AB - Data from 120 patients diagnosed as having renal cell carcinoma (RCC), and treated in an organ-preserving surgical manner were analyzed from 11 participating Austrian urological centers. The male to female ratio was 66:54. The subjects age ranged from 27 to 75 years with mean age of 59 years. The indication for conservative tissue-saving surgery was a solitary kidney in 48 instances, a bilateral RCC in 18 cases and, in 2 patients, a horseshoe kidney tumor. In 52 cases the indication for conservative surgery was a peripheral, easily resectable, low-stage tumor (elective indication). Results were comparable to radical nephrectomy of low-stage tumors especially relating to survival rates. Ninety-nine patients survived and were tumor free at the point of check up (December 1988). Thirteen patients had either local tumor recurrence and/or metastases and 5 patients died from the disease. The operative mortality and the morbidity rate was very low. PMID- 2226590 TI - Regional lymph node metastasis in renal cell carcinoma: incidence, distribution and its relation to other pathological findings. AB - Extended ipsilateral lymphadenectomy performed on 102 patients with renal cell carcinoma revealed 21 patients (21%) having regional lymph node metastasis. Of the 21 patients, 6 (6%) had single-node metastasis and 15 (15%) multiple-node metastasis. PT, pV, pM, cell type and grade were all correlated with regional node metastasis. The metastatic lymph node foci were distributed along the pathways of normal lymphatic drainage. The recurrence of the disease was correlated with lymph node metastasis, indicating that metastasis is one of the prognostic factors. The very close correlation of node metastasis with vein invasion suggests that removal at least of the ipsilateral lymph node might be necessary when removal of a thrombus in the renal vein or vena cava is indicated. PMID- 2226591 TI - Incidental detection of renal tumours by abdominal ultrasonography. AB - One hundred and twenty-six patients with renal cell carcinoma were treated by nephrectomy between 1985 and 1988. They were classified into three groups: group A: 47 patients in whom ultrasonography revealed the renal cancer in the absence of any suggestive clinical signs of tumour; group B: 63 patients who presented with clinical urological signs suggestive of the tumour; group C: 16 patients who presented with general signs leading to the diagnosis. In group A, 50% of the tumours measured between 5 and 10 cm, 51% were located at the lower pole of the kidney and 83% were stage T2. Sixty-six percent of cancers in this group were situated on the right side, indicating that left renal cancers are missed in 16% of cases. In group B, 60% of the tumours measured between 5 and 10 cm, 44% were located at the lower pole and 56% were stage T2. In group C, 60% of the tumours measured between 5 and 10 cm, 50% were located at the upper pole of the kidney and only 38% of the tumours were still stage T2. We can conclude that incidental detection reveals renal tumours at a relatively limited stage (83% of T2), with dimensions smaller than those of the other groups. It is therefore essential for radiologists, ultrasonographists and urologists to investigate the left lumbar fossa and the upper pole of both kidneys very carefully during abdominal or vesico-prostatic ultrasound examinations. PMID- 2226593 TI - The operable renal cell carcinoma. Progress in basic research, diagnosis, surgical and medical therapy. 3rd symposium. Hamburg, November 3-4, 1989. Proceedings. PMID- 2226592 TI - Influence of blood group type on prognosis of transitional cell carcinoma of the urinary bladder. AB - The correlation of blood group to grade, stage and tumor markers at diagnosis and to the subsequent clinical course was investigated in a consecutive retrospective series of 230 patients with primary transitional cell carcinoma of the urinary bladder. The follow-up period was 5-9 years. There were no significant differences in grade, stage or DNA ploidy between patients of blood groups A and O. However, the deletion of ABH blood group isoantigen was found more frequently in tumors from patients of blood group O. Concerning progression of superficial bladder tumors, this was found earlier among patients of blood group O, and in a multivariate analysis this emerged as an independent prognostic factor. The crude and corrected mortality was not significantly higher among patients of group O than among those of other blood groups. PMID- 2226594 TI - Monoclonal antibodies to renal cancer antigens. PMID- 2226595 TI - Implications of insulin-like growth factors in renal cell carcinoma. PMID- 2226596 TI - Immunohistology of renal carcinomas. PMID- 2226597 TI - Renal oncocytoma: prognosis and treatment. PMID- 2226598 TI - Clinically unrecognized renal cell carcinoma. Diagnostic and pathological aspects. PMID- 2226599 TI - Pros and cons of retroperitoneal lymphadenectomy in operable renal cell carcinoma. PMID- 2226600 TI - The role of nephron-sparing surgery for renal cell carcinoma. PMID- 2226601 TI - Operative management of renal cell carcinoma with suprahepatic intracaval neoplastic extension. PMID- 2226602 TI - DNA content in renal cell carcinoma and its clinical significance. PMID- 2226603 TI - Value of DNA analysis for treatment of renal cell carcinoma. PMID- 2226605 TI - Prognostic parameters of renal cell carcinoma. PMID- 2226604 TI - New approaches to the evaluation of the metastatic ability of renal cancer and new approaches to chemotherapy. PMID- 2226606 TI - Tumor heterogeneity of renal cell carcinoma. PMID- 2226607 TI - Antigen expression in renal cell carcinoma. Correlation with histological grade, pathological stage and development of distant metastasis. PMID- 2226608 TI - The biology of renal cancer: the influence of nephrectomy. PMID- 2226609 TI - Immunotherapy for advanced renal cell cancer: the role of radical nephrectomy. PMID- 2226610 TI - Immunotherapy of advanced renal cancer. PMID- 2226611 TI - The operable renal cell carcinoma: summary and conclusions. PMID- 2226612 TI - The Heinrich Warner Prize 1989: the use of differential hybridization analysis to identify markers for diagnosis of urogenital cancer. PMID- 2226613 TI - Cytomorphological typing of renal cell carcinoma--a new approach. PMID- 2226614 TI - Story composition skills of middle-grade students with learning disabilities. AB - This study examined the story composition abilities of learning disabled (LD) and normally achieving young adolescents as indicated by measures of writing category, cohesion, and fluency. Findings suggest that although adolescents with learning disabilities have a rudimentary knowledge of story form, this knowledge is less well developed than that of their nondisabled peers. Students with learning disabilities also had greater coherence problems in their writing and were less fluent writers. Several important age trends were noted when results of this investigation were compared with outcomes from a similar investigation involving younger students. PMID- 2226616 TI - Prediction is not the only measure of a plan: a response to Marston. PMID- 2226615 TI - Nonaversive treatment of high-rate disruption: child and provider effects. AB - A multiple baseline across three providers showed that each provider, using only differential reinforcement of incompatible behavior (DRI), substantially reduced high-rate out-of-seat behavior in a highly disruptive 4-year-old boy with severe disabilities. During the experiment, duration of the boy's in-seat behavior expanded from less than 1 min to 20 min. Furthermore, during the intervention, the providers' use of physical restraint decreased to near-zero levels, even though restraint and DRI could be used together. Although not specifically targeted, the boy's appropriate toy play also increased during DRI. PMID- 2226617 TI - Effects of corticotropin-releasing factor on central respiratory activity. AB - Effects of corticotropin-releasing factor (CRF) on central regulation of respiration were studied in urethane-anaesthetized, vagotomized, paralyzed and artificially ventilated rabbits. Injections of CRF into the IVth cerebral ventrile (i.c.v.) resulted in an increase of the neuronal tidal volume (nVt), but had only minor effects on the duration of respiratory phases. Microinjection of CRF into the ventral parabrachial region of the pons (pneumotaxic center) resulted in a reduction of nVt and of the respiration rate. Respiratory effects of CRF administered i.c.v. or into the pontine parabrachial region were antagonized by alpha-helical-CRF, indicating a receptor-mediated action of CRF. Respiratory effects of CRF were not significantly affected after blocking ganglionic transmission with chlorisondamine. Neither mean arterial blood pressure nor heart rate were significantly affected by the injection of CRF into the IVth ventricle or the rostral pons. Results suggest an involvement of CRF in the central regulation of respiratory movements. CRF may be involved in the adaptation of respiration to stress. PMID- 2226618 TI - High-affinity binding of mequitamium iodide (LG 30435) to muscarinic and histamine H1 receptors. AB - Mequitamium iodide (LG 30435) is a novel quaternary ammonium phenothiazine with potential as an anti-asthmatic agent. In vitro binding experiments were performed in order to clarify the molecular mechanisms underlying its biological activity. Mequitamium iodide was found to bind with high affinity only to histamine H1 receptors in rat brain membranes (Ki = 9 nM) and to muscarinic acetylcholine receptors in various tissues homogenates (Ki = 12-77 nM) with no clearcut selectivity for any of the known subtypes. The interaction with muscarinic receptors in rat cerebral cortex and lung parenchyma was competitive, as showed by saturation studies. Lower affinity values (Ki = 1-10 microM) were found for serotonin 5-HT2, platelet-activating factor (PAF), verapamil and beta-adrenergic agents. These results indicate that both the potent antimuscarinic and antihistamine and the relatively weak anti-PAF pharmacological effects of mequitamium iodide may be explained by the direct interaction of the substance with the respective receptors. PMID- 2226619 TI - Pharmacological and functional analysis of a novel serotonin receptor in the rat hippocampus. AB - Administration of serotonin (5-hydroxytryptamine, 5-HT) to pyramidal cells of the CA1 region of the hippocampus results in a hyperpolarizing response which is followed by a rebound depolarization and a decrease in the calcium-activated afterhyperpolarization (AHP). While the hyperpolarizing response has been previously shown to be mediated by receptors of the 5-HT1A subtype, the identity of the receptor(s) involved in the depolarizing response and decrease of the AHP have not been identified. In the present study the effectiveness of a series of 5 HT receptor antagonists in blocking the membrane depolarization and reduction of the AHP was assessed. While a variety of 5-HT1 and 5-HT2 antagonists were found to be ineffective, the substituted benzamide BRL 24924 was found to be a potent and selective antagonist of the 5-HT-induced depolarization and decrease in the AHP in this region. This effect however appeared unrelated to the ability of this compound to block 5-HT3 receptors, as ICS 205-930 and MDL 72222 were markedly less efficacious in blocking these effects of 5-HT. Upon blockade of 5-HT1A receptors, 5-HT elicits a depolarization which is accompanied by a marked increase in excitability. These effects were also dose-dependently antagonized by BRL 24924. The present results thus suggest the presence in the CA1 region of the hippocampus of a novel 5-HT receptor at which BRL 24924 functions as a selective antagonist and which is capable of mediating slow excitatory responses in central neurons. PMID- 2226620 TI - Identification and pharmacological properties of binding sites for the atypical thiazide diuretic, indapamide. AB - [3H]Indapamide bound to a single class of binding sites in pig renal cortex membranes with a dissociation constant Kd = 35 +/- 13 nM and a binding site density Bmax = 40 +/- 9 pmol/mg of protein. [3H]Indapamide binding was inhibited by the carbonic anhydrase inhibitor, acetazolamide, and by thiazide diuretics with the following rank order of potency: chlorothiazide greater than hydrochlorothiazide approximately metolazone greater than hydroflumethiazide. The effect of the latter drugs to inhibit [3H]indapamide binding was not related to their activity as thiazide diuretics, but was significantly correlated with their inhibitory effect on carbonic anhydrase II. These results suggest that the major renal binding site of [3H]indapamide is a membrane form of carbonic anhydrase. Inhibition of carbonic anhydrase may play a role in the antihypertensive effect of indapamide. PMID- 2226621 TI - Beneficial hemodynamic effects of two weeks' milrinone treatment in conscious rats with heart failure. AB - Milrinone is a phosphodiesterase inhibitor which combines vasodilating effects with inotropic effects. Hemodynamic improvement after acute administration and increased survival with chronic milrinone therapy in rats with heart failure have been reported before, and suggest long-term hemodynamic improvement. However, no detailed hemodynamic studies are available on prolonged milrinone therapy in rats with heart failure. Therefore, the hemodynamic effects of 2 weeks' milrinone therapy were now investigated in conscious rats with heart failure due to myocardial infarction. The effects were compared to hemodynamic changes after acute administration. Acute milrinone increased the baseline cardiac output in infarcted rats by increasing heart rate rather than stroke volume. However, the maximal cardiac output achieved when the heart was stimulated through a volume load was improved due to increased stroke volume as well as increased heart rate. The increase in maximally stimulated cardiac output after acute milrinone was found to be related to infarct size. Two weeks' milrinone therapy in chronically infarcted rats dose dependently restored the hemodynamic changes which were caused by infarction. In contrast to acute administration, two weeks' milrinone restored cardiac function without an increase in heart rate. The effects were achieved at a rate of administration which presumably has no acute inotropic effects. The data indicate that acute milrinone in infarcted rats has vasodilating effects. Positive inotropic effects, possibly masked by concomitant venodilatation at baseline conditions, became overt after stimulation by volume loading. Long-term milrinone dose dependently restored cardiac function in infarcted rats without effects on heart rate or mean arterial pressure, suggesting that different mechanisms may be involved. PMID- 2226622 TI - The hypotensive and negative chronotropic effects of dehydroevodiamine. AB - The cardiovascular effects of dehydroevodiamine, an alkaloid isolated from Evodia rutaecarpa Jussieu, were studied in both in vivo and in vitro experiments. The in vivo experiments revealed that i.v. administration of dehydroevodiamine elicited a slight but significant reduction in blood pressure and a marked decrease in heart rate which was confirmed by an increased cycle length of the electrocardiogram. However, a hemodynamic experiment with microspheres showed that the total peripheral resistance was not altered by dehydroevodiamine. The blood flows of various organs were not significantly changed except those of kidney and skin, in which blood flow was decreased. In vitro, the spontaneously beating atria were significantly suppressed by dehydroevodiamine in a dose dependent manner. These findings suggested an important effect of dehydroevodiamine in suppressing the heart, which may largely contribute to the hypotensive effect of this alkaloid. However, its vasodilator effect on hindquarter muscles cannot be neglected. PMID- 2226624 TI - Cultured endothelial cells maintain their L-arginine level despite the continuous release of EDRF. AB - Endothelial cells cultured from bovine aorta and grown on microcarrier beads contain 107 +/- 9 microM L-arginine (Arg; n = 11). When packed into a jacketed chromatography column and perfused with Krebs solution, the cells showed a substantial and sustained release of endothelium-derived relaxing factor (EDRF) for up to 2 h, which was further enhanced by infusions of adenosine diphosphate (4 microM). In contrast to other amino acids, such as L-alanine, L-aspartate, L glutamine, L-glutamate or L-serine, which showed a time-dependent decrease to less than 30% of their original level within 2 h, Arg remained at control levels for 30 min and decreased only by 25% after 2 h. Thus endothelial cells can generate Arg from an intracellular source to maintain their Arg level despite the continuous formation of EDRF. PMID- 2226623 TI - Content and contractile effect of arginine vasopressin in rat urinary bladder. AB - The contractile response of normal male rat urinary bladders to exogenous arginine vasopressin (AVP) and the AVP content of normal and denervated bladders were investigated. In isolated detrusor strips, the maximal response to AVP was about 12% of the contraction elicited by KCl (124 mM), and the EC50 value was 1.03 +/- 0.13 x 10(-8) M. The response to transmural nerve stimulation was not affected by the presence of AVP. Addition of an AVP receptor antagonist strongly reduced the response to exogenous AVP, but did not affect contractions in response to nerve stimulation. In normal bladders, the concentration of immunoreactive (ir) AVP was 29 +/- 6.0 x 10(-15) mol/g. Three days after denervation the bladders had increased 2.4-fold in weight. At this time, the concentration of irAVP was not different from the control value, but the total content had increased significantly. Characterization of bladder irAVP by reverse phase HPLC revealed that 66.5% of the total immunoreactivity eluted in the position of synthetic AVP. The results suggest a non-neuronal localization of bladder irAVP. PMID- 2226625 TI - Stereospecific inhibition of non-opioid defeat analgesia in male mice by MDL 72832, a selective 5-HT1A receptor agonist. AB - The effects of MDL 72832, a potent and stereoselective ligand for 5-HT1A sites, on basal nociception and non-opioid defeat analgesia in male mice were examined. Neither (+)- nor (-)-MDL 72832 significantly altered basal tail-flick latencies. In contrast, (-)-MDL 72832 potently inhibited defeat analgesia (0.1-0.5 mg/kg i.p.), with similar effects produced by (+)-MDL 72832 only at substantially higher doses (3.0-5.0 mg/kg i.p.). These data clearly demonstrate a stereoselective action of this 5-HT1A ligand on non-opioid defeat analgesia. PMID- 2226626 TI - Inhibition of nitric oxide synthesis reduces the hypotension induced by bacterial lipopolysaccharides in the rat in vivo. AB - E. coli lipopolysaccharide (LPS; 15 mg kg-1 i.v.) produced a long-lasting reduction in mean arterial blood pressure (MAP) in the anaesthetized rat. Inhibition of nitric oxide endothelium-derived relaxing factor (EDRF) synthesis with NG-monomethyl-L-arginine (MeArg, 1 mg kg-1 min-1 i.v. for 30 min) produced an increase in MAP and largely attenuated the LPS-induced hypotension; both effects were significantly reversed with L-arginine (6 mg kg-1 min-1 i.v.). When compared to MeArg, phenylephrine (300 mg kg-1 h-1 i.v.) produced a similar pressor response, but much less attenuation of the hypotensive response to LPS. Thus, a stimulation of EDRF release contributes to the LPS-induced hypotension in the anaesthetized rat. PMID- 2226627 TI - Opposite effects of endothelin-1 and Big-endothelin-(1-39) on renal function in rats. AB - Bolus injections of Big-endothelin-(1-39) (Big-ET; 0.1-3.0 nmol/kg) induced a dose-dependent diuretic and natriuretic response in conscious Sprague-Dawley rats. Endothelin-1-(1-21) (ET-1; 1 nmol/kg) induced an opposite effect with almost complete renal shut down. Renal blood flow did not change with Big-ET but was reduced by half with ET-1. Although the maximal pressor responses of the two peptides were comparable the renal resistance did not change with Big-ET but increased 4-fold with ET-1. These data suggest that Big-ET may have a different mechanism of action than ET-1. PMID- 2226628 TI - The polyamine synthesis inhibitor alpha-difluoromethylornithine blocks NMDA induced neurotoxicity. PMID- 2226629 TI - Phosphoramidon, a metalloproteinase inhibitor, suppresses the hypertensive effect of big endothelin-1. AB - Intravenous (i.v.) injection of big endothelin-1 (1-39, 0.05-1.0 nmol/kg) to anaesthetized rats produced a dose-dependent and long-lasting hypertensive effect, the magnitude of which was similar to that evoked by ET-1 (1-21). In animals given phosphoramidon (0.25 mg/kg per min i.v.), a metalloproteinase inhibitor, the hypertensive effect of big endothelin-1 was markedly attenuated. The same dose of phosphoramidon did not influence the endothelin-1-induced hypertensive effect. The possibility that big endothelin-1 is converted to endothelin-1 by a phosphoramidon-sensitive metalloproteinase in vivo warrants further attention. PMID- 2226630 TI - Temperature dependence of angiotensin II-mediated depolarisation of the rat isolated nodose ganglion. AB - The ability of angiotensin II (A II) and 5-hydroxytryptamine (5-HT) to depolarise the rat isolated nodose ganglion preparation was examined. 5-HT depolarised the nodose ganglion, both at room temperature (20-24 degrees C) and at 35-37 degrees C. However, A II depolarised the nodose ganglion only under the latter condition, and these responses were blocked by the A II receptor antagonist saralasin. This study extends previous findings which have demonstrated A II binding sites on the nodose ganglion and axon, and identifies the rat nodose ganglion as a sensitive preparation in which to study the interactions between neuronal A II receptor activation and its blockade by A II receptor antagonists. PMID- 2226631 TI - Modulatory role of endogenous nitric oxide in pulmonary circulation in vivo. PMID- 2226632 TI - Neuroprotective effect of memantine demonstrated in vivo and in vitro. AB - The purpose of the present study was to test whether the anticonvulsant, memantine (1-amino-3,5-dimethyladamantane), can protect neurons against hypoxic or ischemic damage. To this end, we used a rat model of transient forebrain ischemia and cultured neurons from chick embryo cerebral hemispheres. Ischemia was induced for 10 min by clamping both carotid arteries and lowering the mean arterial blood pressure to 40 mm Hg; the rats were allowed to recover for 7 days. Cultured neurons were made hypoxic with 1 mmol/l NaCN added to the incubation medium for 30 min followed by a recovery period of 3 days. The possible effects of memantine were compared with those produced by a typical non-competitive NMDA antagonist, dizocilpine. Similar effects were obtained with both drugs. The drugs reduced the damage caused by transient ischemia to neurons of the hippocampal CA1 subfield. Memantine (10 and 20 mg/kg) had a dose-dependent effect when administered intraperitoneally to the rats 1 h before ischemia. Dizocilpine was active in this model at a dosage of 1 mg/kg. When administered after ischemia, 10 mg/kg memantine significantly protected CA1 neurons against ischemic damage. Furthermore, the drugs protected cultured neurons against hypoxic damage. The lowest effective concentration was 0.1 mumol/l for dizocilpine and 1 mumol/l for memantine. Thus, memantine possesses neuroprotective activity but is less potent than dizocilpine. PMID- 2226633 TI - A comparison of the haemodynamic profiles of Ro 31-6930, cromakalim and nifedipine in anaesthetised normotensive rats. AB - The regional haemodynamic profiles of Ro 31-6930, cromakalim and nifedipine were compared using pulsed Doppler flowmetry in the anaesthetised rat. In order of potency, Ro 31-6930 (0.1-300 micrograms/kg), cromakalim (1-300 micrograms/kg) and nifedipine (1-1000 micrograms/kg) produced dose related falls in mean arterial pressure. The hypotensive effects of Ro 31-6930 and cromakalim were accompanied by reflex tachycardia. All three agents reduced renal vascular resistance by 30 50%. Cromakalim exerted a selective action on this vascular bed. Similar maximal reductions in mesenteric vascular resistance (37-50%) were observed; however, cromakalim was the least potent on this vascular bed. Maximal reductions in iliac vascular resistance (65-78%) were observed, with an order of potency as observed on mean arterial pressure. Qualitative differences in the regional haemodynamic profiles of Ro 31-6930, cromakalim and nifedipine are evident from this study. The different profiles of Ro 31-6930 and cromakalim may reflect structural differences between the pharmacophores of these compounds. PMID- 2226634 TI - Distinct stimulatory effect of platelet-activating factor on prostaglandin I2 and thromboxane A2 biosynthesis by rat dental pulp. AB - Platelet-activating factor (PAF-acether), but not lyso PAF, stimulated the production of both PGI2 and TXA2 by rat dental pulp tissue in vitro. However, there were differences in the dose- and time-dependence of the stimulatory effects. PAF-acether antagonists, Bn 52021, CV 3988 and kadsurenone, dose dependently inhibited PAF-acether-induced PG production. BN 52021, CV 3988 also dose dependently inhibited TX production, but kadsurenone was almost without effect on TX production. Pretreatment of the tissues with PAF-acether or phorbol 12-myristate 13-acetate completely abolished the effect of the second challenge with PAF-acether. The stimulatory effects of PAF-acether and the calcium ionophore A23187 on PGI2 production were completely blocked by removal of extracellular calcium, whereas the effects on TXA2 production were not. TMB-8, an intracellular calcium antagonist, completely inhibited PAF-acether-induced PG production, whereas it slightly inhibited TX production. H-7, a protein kinase C inhibitor, and neomycin, a phospholipase C inhibitor, completely inhibited PAF acether-induced PG and TX production, whereas W-7, a calmodulin inhibitor, did not. These results suggest that PAF-acether stimulates PGI2 and TXA2 production in rat dental pulp by interacting with distinct PAF-acether receptors, and that these receptors are coupled to independent signal transduction pathways which have a different dependence on extra- and intracellular calcium. PMID- 2226635 TI - Inositol hexakisphosphate stimulates 45Ca2+ uptake in anterior pituitary cells in culture. AB - Inositol hexakisphosphate (InsP6) is thought to act as an intracellular signal molecule in the central nervous system. We report that InsP6 stimulates 45Ca2+ uptake in cultured anterior pituitary cells. This effect is concentration dependent, is mimicked by inositol-pentakis phosphate (InsP5) but not by inositol tetrakis phosphate (InsP4), is present after 2 min of incubation, is independent of extracellular Na+ and insensitive to nifedipine and verapamil. These results suggest that InsP6, a putative metabolite of the inositol cycle, may regulate transmembrane mechanism in the pituitary. PMID- 2226636 TI - Inhibitory effects of a novel antiatheromatous agent, E5050, on aortic smooth muscle cell proliferation, in vitro. AB - The effect of a novel antiatheromatous agent, N-(3-[4'-(2'',6'' dimethylheptyl)phenyl]butanoyl)ethanolamin e (E5050), on the proliferation of porcine aortic smooth muscle cells was studied in vitro. E5050 dose-dependently inhibited DNA synthesis as well as proliferation of cells stimulated with 10% fetal calf serum with no cytotoxic effects. An inhibitory effect of E5050 on DNA synthesis was also confirmed in cells stimulated with human platelet extract and with a combination of platelet-derived growth factor and human plasma-derived serum. DNA synthesis in smooth muscle cells stimulated with other mitogens, such as fibroblast growth factor and insulin, was inhibited by E5050 and this inhibitory effect was positively correlated with the E5050 uptake into smooth muscle cells. These results indicate that E5050 inhibits smooth muscle cell proliferation stimulated by various mitogenic factors. It is suggested that E5050 prevents atherogenesis and inhibits the progression of fibromuscular lesions by interfering with the proliferation of arterial smooth muscle cells. PMID- 2226637 TI - P2 purinoceptor-mediated inositol phosphate formation in relation to cytoplasmic calcium in DDT1 MF-2 smooth muscle cells. AB - The effect of P2 purinoceptor stimulation on inositol phosphate (InsP) formation in relation to the intracellular Ca2+ concentration was measured in vas deferens DDT1 MF-2 smooth muscle cells. The different [3H]myo-inositol-labelled InsP fractions were analyzed by high performance liquid chromatography and intracellular Ca2+ was determined by measuring fluorescence using Indo-1 as indicator. Stimulation with ATP (10(-4) M) resulted in an enhanced formation of inositol mono-, bis-, tris- and tetrakisphosphate (InsP1, InsP2, InsP3 and InsP4), but no changes occurred in the formation of inositol pentakis- and hexakisphosphate (InsP5 and InsP6). The putative second messenger Ins(1,3,4,5)P4 rapidly increased after addition of the agonist, reaching a maximum after about 2 min. The isomer Ins(1,4,5)P3 showed a delayed rise starting after about 2 min. The formation of Ins(1,3,4,5)P4 in the presence of ATP (2 min) was concentration dependent, reaching a half maximal value at about 50 microM of the agonist. The intracellular Ca2+ concentration showed an initial increase after P2 purinoceptor stimulation, reaching a plateau after 2 min. Both the top of the initial phase and the plateau value of the response reached a half maximal value at an ATP concentration of about 7 microM. This Ca2+ response could be evoked repeatedly by ATP and was not affected by diltiazem (10(-5) M). In the absence of external Ca2+, the internal Ca2+ concentration increased transiently in the presence of ATP without showing the plateau phase. This response could be evoked only once under Ca2(+)-free conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226638 TI - Identification and initial characterization of high-affinity [3H]dextrorphan binding sites in rat brain. AB - We have identified specific high-affinity [3H]dextrorphan binding sites in rat forebrain. [3H]Dextrorphan binds saturably and reversibly to an apparently homogenous class of sites characterized by a Bmax of 2.62 +/- 0.06 pmol/mg protein and KD of 60 +/- 4 nM. Glycine and glutamate independently increase [3H]dextrorphan binding in a concentration-dependent manner. The pharmacological profiles of [3H]dextrorphan binding characterized by equilibrium competition experiments together with these data suggest that [3H]dextrorphan labels a site at or near the N-methyl-D-aspartate receptor. PMID- 2226639 TI - GTP modulates [125I]iodomelatonin binding to a picomolar-affinity site in the Syrian hamster hypothalamus. AB - Saturation binding experiments conducted with [125I]iodomelatonin at 0-4 degrees C in the Syrian hamster hypothalamus, revealed a single nanomolar-affinity site which was not affected by GTP. In contrast, incubation at 30 degrees C revealed two distinct binding sites with picomolar and nanomolar affinities, respectively. GTP caused a significant decrease in the affinity of only the picomolar site but did not alter its density; control: Kd = 43 +/- 6 pM, Bmax = 1.7 +/- 0.3 fmol/mg protein; GTP (1 mM): Kd = 250 +/- 52, Bmax = 3.9 +/- 2.6 fmol/mg protein. The foregoing indicates that the affinity of the putative melatonin receptor in the hamster hypothalamus is modulated by a regulatory G protein. PMID- 2226640 TI - Immortalization of primary cells by DNA tumor viruses. AB - Cellular senescence is characterized by a decline in sensitivity to growth factors resulting in cessation of cellular growth. The expression of cellular or viral oncogenes may result in the establishment of cell lines with unlimited proliferative potential ("immortalization"). A variety of viral and cellular oncogenes have been reported to immortalize cells, suggesting that multiple mechanisms may lead to an escape from senescence. Immortalization has been reported to occur as a result of an interaction of viral proteins with cellular suppressor gene products or may result from the elevated expression of "transforming" oncoproteins (such as the polyomavirus middle-t antigen). Here we speculate that a selection for cells with a further decreased probability of cell cycle withdrawal can occur during the growth of cells expressing viral early genes, resulting in a process of tumor progression. Explaining immortalization in terms of mitogenic stimulation due to the expression of viral oncogenes followed by genetic/epigenetic changes may help to explain why lytic DNA viruses have a biological activity which may not be necessary for their life cycle. PMID- 2226641 TI - Interleukin-1-induced suppression of type II collagen gene transcription involves DNA regulatory elements. AB - Interleukin-1 is a proinflammatory polypeptide that influences cartilage macromolecular degradation and synthesis. Since previous studies have suggested that interleukin-1 may inhibit type II collagen synthesis, we have studied the mechanism of inhibition of type II collagen synthesis by interleukin-1. When rabbit articular chondrocytes were treated with purified recombinant interleukin 1 beta or macrophage-conditioned medium, the synthesis and assembly of type II collagen into the extracellular matrix were greatly reduced. The inhibition was concentration-dependent and occurred within 10 h of treatment with interleukin-1, with greater inhibition occurring at 30 h. The reduced level of collagen synthesis correlated with a reduction in the steady-state mRNA levels coding for type II collagen, as measured by a Northern blot analysis. This further correlated with a reduction in the transcription of type II collagen gene, as determined by nuclear run-on experiments. Finally, transfection studies using plasmid constructs containing DNA regulatory sequences from the type II gene, coupled to a reporter gene (CAT), revealed that in comparison to control chondrocytes, interleukin-1 treated cells showed a reduced level of CAT activity. These studies demonstrate that the inhibition of collagen type II synthesis by interleukin-1 is due to a reduction in the transcription of the type II collagen gene and that the reduction in gene transcription involves DNA regulatory sequences that determine type II collagen gene expression. PMID- 2226642 TI - Growth inhibition of mitogen-stimulated fibroblasts induced by double-stranded RNA depends on cell density. AB - Polyinosinic-polycytidylic acid [poly(I:C)], a synthetic double-stranded RNA, is an inhibitor of mitogen-induced proliferation of normal fibroblasts. We show that this inhibition depends strongly on cell density. While cultures with densities at or above confluence are completely inhibited by poly(I:C) in their proliferative response to epidermal growth factor (EGF), the proliferation of sparse (subconfluent) cultures is only delayed. Conditioned medium from dense fibroblasts exposed to poly(I:C) inhibits EGF stimulation of sparse cells, indicating that the inhibition is, at least in part, mediated by a factor released from the cells. Preincubation of quiescent cultures with poly(I:C) renders the cells refractory to the inhibitory effects of poly(I:C). This desensitization correlates with a decreased production of the inhibitor. Since the inhibition of mitogenic stimulation by poly(I:C) is completely overcome by antisera recognizing interferon-beta (IFN-beta) and interleukin-6 (IL-6), we tested the effect of IL-6 and IFN-beta on EGF mitogenicity. None of the available IL-6 preparations had any effect on cell cycle entry. IFN-beta caused a dose dependent delay of cell division but did not affect the density-dependent proportion of cells entering the cell cycle in response to EGF. Thus, IFN-beta cannot be the sole mediator of the poly(I:C)-induced inhibition. In the presence of dexamethasone, poly(I:C) did not inhibit EGF mitogenis. Indeed, the combined presence of poly(I:C) and dexamethasone did more than just restore the density dependent control levels of EGF stimulation; most cells entered the cell cycle even at extremely high cell densities. Thus, poly(I:C) in combination with dexamethasone could deactivate the cell density-dependent negative control of proliferation. PMID- 2226643 TI - Different effects of TPA on two skin-derived cell lines: murine (HEL-30) and human (NCTC) epidermal cells. AB - 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a rapid activation of protein kinase C in a murine (HEL-30) and in a human (NCTC) epidermal cell line. In HEL 30 cells, protein kinase C activation is followed by ornithine decarboxylase stimulation and cell proliferation, events inhibited by H-7, a specific inhibitor of protein kinase C. TPA in NCTC cells inhibited the basal ornithine decarboxylase activity and cell growth, whereas H-7 did not modify TPA effect. The response of NCTC cells was not due to direct toxicity of TPA. These data confirm that in murine epidermal cells, the proliferation induced by TPA is mediated by protein kinase C, whereas in a human skin-derived cell line these events are not or inversely associated. PMID- 2226644 TI - Differentiation of newborn rat preadipocytes in culture: effects of insulin and dexamethasone. AB - A preadipocyte cell population isolated from the inguinal tissue of 3-day-old rats converts at confluence into mature adipocytes when cultured with insulin (10(-9) M). Insulin is necessary only from Day 4 postplating. If the addition of insulin is further delayed, the proportion of cells which will undergo adipose conversion decreases. A loss of the differentiation competence is also observed when the cells are allowed to proliferate (seeding at a low density in a serum containing medium). A preexposure of the primary cells to dexamethasone during the insulin-insensitive period (Days 0-4) accelerates the subsequent "insulin dependent" adipose conversion. In order to produce its effect, dexamethasone needs only to be present for 4 h on Day 2 postplating. The effect of dexamethasone is probably due neither to inhibition of cell proliferation nor to induction of the cell content of insulin receptors. The evolution of G3PDH enzyme activity as well as of G3PDH protein and mRNA was used as an indicator of the differentiation process. The enzyme accumulates to a low extent during culture in the absence of insulin. When insulin is present, the enzyme level is dramatically increased (maximum on Day 11). Dexamethasone pretreatment (Days 0-4, or 4 h on Day 2) accelerated the G3PDH enzyme activity increase as well as protein and mRNA accumulation. This was also true in cells maintained in insulin-free medium; however, in this case, the increase in the enzyme activity was limited to the first 8 days of culture and full differentiation did not take place. We conclude that: (1) the rat preadipocytes are committed to differentiate, requiring insulin as a sufficient physiological stimulus; (2) the differentiation program is progressively lost after greater than 4 days of culture without insulin and more rapidly if the cells are allowed to undergo divisions; and (3) dexamethasone accelerates the insulin-dependent adipose conversion but alone does not ensure the complete differentiation process. PMID- 2226645 TI - Membrane fatty acid changes during the cell cycle of CV-1 cells. AB - Monolayers of CV-1 cells were synchronized at the G1/S boundary of the cell cycle by a 24-h 2 mM thymidine blockade. Uptake of tritiated thymidine indicated that the peak DNA synthesis occurred 6-8 h after release from the block and that cell cycle time was 18-20 h. The fatty acid composition of phospholipids extracted from cells at 0, 7, and 18 h postblockade was measured by gas chromatography. The results indicate cyclic changes in membrane fatty acids with a significant increase in long-chain polyunsaturated fatty acids during the DNA synthesis phase (S phase) of the cell cycle. PMID- 2226646 TI - Effect of TGF-beta 1, TGF-beta 2, and bFGF on chick cartilage and muscle cell differentiation. AB - In insulin containing defined medium TGF-beta 1, TGF-beta 2, and bFGF all stimulate chondrogenic differentiation in high-density micromass cultures of distal limb bud mesenchyme cells of chick embryos. In addition bFGF inhibits myogenic differentiation, while TGF-beta 1 and TGF-beta 2 appear to have no effect. TGF-beta 1 and bFGF together act additively to enhance chondrogenesis, while TGF-beta blocks the bFGF inhibitory action on myoblasts, thus allowing them to differentiate. In the absence of insulin, the inhibitory effect of bFGF on muscle cell differentiation is reduced; cartilage differentiation in the presence of the above growth factors is also slightly reduced. PMID- 2226647 TI - Nucleolar transcriptional activity in mouse Sertoli cells is dependent on centromere arrangement. AB - Experimental evidence suggests that centromere arrangement is relevant to the expression of ribosomal genes in murine Sertoli cells. Nuclei endowed with a nucleolus inactive in rRNA synthesis presented several clusters, each containing a bunch of individual centromeres. RNA polymerase I was not cytochemically detected in the nucleolar structure, which contained only small amounts of fibrillarin. In the course of nucleolar activation, the centromeres within the separate clusters became fused into larger centromeric bodies. Synthesis of precursor rRNAs and their processing were visualized by strong nucleolar fluorescence signals using antibodies to RNA polymerase I and fibrillarin. PMID- 2226648 TI - Serum-induced cytosolic calcium movements and mitogenesis in cultured preosseous chondrocytes. AB - The differentiation of preosseous chondrocytes begins with the proliferation of resting cells and results in the expression of the hypertrophic phenotype. The effect of fetal calf serum on chondrocyte mitogenesis and intracellular Ca2+ concentration was studied in resting and hypertrophic cells in primary culture. Resting chondrocytes respond to the growth stimulus with immediate release of Ca2+ from intracellular stores and with opening of the plasma membrane Ca2+ channels. These events may be related to the elevated [3H]thymidine incorporation observed after serum exposure. In contrast, in hypertrophic chondrocytes the lower rate of DNA synthesis seems to be coupled with a lower activity of the Ca2+ signaling mechanism and, probably, with reduced intracellular calcium stores. It is proposed that expression of the Ca2+ signaling mechanism may be modulated during the differentiation of preosseous chondrocytes. PMID- 2226649 TI - Effect of long-term hypoxia on cultured aortic and pulmonary arterial endothelial cells. AB - In a previous study, we found a marked difference in the release of a cytokine, neutrophil chemoattractant activity (NCA), from cultured endothelial cells exposed to acute decreases in ambient oxygen, depending on the vascular bed of origin. In the current study, we used this cytokine to evaluate the effect of long-term exposure to decreased oxygen on endothelial cell function. We found that, in aortic and pulmonary arterial endothelial cells maintained for months in decreased ambient oxygen (10 or 3% oxygen), exposure to acute decreases in ambient oxygen caused a change in the pattern of NCA release; however, the differential response between the two cell types persisted. Aortic endothelial cells release NCA when exposed acutely to a level of oxygen below that in which they have been chronically maintained. In contrast, pulmonary arterial endothelial cells release NCA only when exposed to 0% oxygen acutely, but only if grown chronically in 10% oxygen; otherwise there was no release of NCA. As another indicator of endothelial cell function, we evaluated the effects of acute hypoxic exposure on prostacyclin production by endothelial cells maintained in 21 or 3% oxygen. If grown in 21% oxygen, both cell types decreased prostacyclin production upon exposure to 0% oxygen. However, when grown in 3% oxygen, only aortic endothelial cells decreased prostacyclin production when exposed acutely to 0% oxygen; pulmonary arterial endothelial cell prostacyclin production did not change. This study demonstrating the persistence of a differential pattern of NCA release and the appearance of a differential pattern of prostacyclin production after a long-term decrease in environmental oxygen suggests that the capacity of certain vascular endothelial cells to respond to decreases in oxygen concentration is carried by the cell throughout its existence. Thus, in certain situations, vascular endothelial cells may be important in sensing acute decreases in ambient oxygen. PMID- 2226650 TI - Changes in the DNA polymerase beta gene expression during development of lung, brain, and testis suggest an involvement of the enzyme in DNA recombination. AB - Changes in the expression pattern of DNA polymerase beta gene during rat lung, brain, and testis development have been investigated. A decrease in the level of beta-pol mRNA was observed during postnatal development of lung and brain. By contrast, an almost 20-fold increase in the level of beta-pol mRNA was observed during spermatogenesis. For most adult rat tissues the abundance of beta-pol mRNA was low compared with that of beta-actin mRNA. Northern blot analysis revealed four distinct transcripts hybridizing to beta-pol probes. At least two of them, 1.4 kb and 4.0 kb, were products of a beta-polymerase gene. The changes in the expression pattern during lung and brain development, and during spermatogenesis, suggest involvement of DNA polymerase beta in gap-filling DNA synthesis during recombination. PMID- 2226651 TI - Correlation between chemotactic peptide-induced changes in chlorotetracycline fluorescence and F-actin content in human neutrophils: a role for membrane associated calcium in the regulation of actin polymerization? AB - Several observations indicate that the triggering event for receptor-mediated actin polymerization takes place in or close to the plasma membrane. Stimulation of human neutrophils with the chemotactic peptide formylmethionyl-leucyl phenylalanine (fMet-Leu-Phe) causes rapid and transient changes in both chlorotetracycline (CTC) fluorescence and the cellular content of filamentous actin (F-actin), thus suggesting a regulatory role for membrane-bound calcium in actin polymerization. In the present study, tetracaine, a proposed antagonist to membrane-bound calcium, totally inhibited the rebinding of the membrane calcium released by fMet-Leu-Phe. This was accompanied by a magnified and sustained increase in the cellular content of F-actin. In agreement, N-ethylmaleimide, an inhibitor of motile functions, completely abolished the fMet-Leu-Phe-triggered changes in both CTC fluorescence and F-actin content and rapidly reversed the responses when added after the peptide. The tumor promoter phorbol-12-myristate 13-acetate, caused only small changes in CTC fluorescence and F-actin content, and reduced a subsequent fMet-Leu-Phe-induced CTC response and actin polymerization. Inhibition of the breakdown of phosphatidylinositol 4,5 bisphosphate, by calcium depletion, had no significant effects on the fMet-Leu Phe-induced CTC response and alterations in F-actin content, whereas pretreatment with pertussis toxin totally inhibited both these responses. Consequently, the strong correlation between changes in CTC fluorescence and F-actin content, found in this study, suggests a triggering or modulating role of membrane-associated calcium on actin polymerization in human neutrophils. PMID- 2226652 TI - Expression of human chromosomal proteins HMG-14 and HMG-17 in Saccharomyces cerevisiae. AB - The cDNAs coding for human chromosomal proteins HMG-14 and HMG-17 were cloned into yeast expression vector pBM150, under the control of the Gal10 promoter. Northern analysis of transformed yeast cells revealed that both cDNAs were efficiently transcribed. Western analysis indicated that the mRNAs were translated into authentic proteins. Expression of human HMG proteins in yeast cell did not produce detectable phenotypic changes, as measured by the growth rate of the yeast cells under a variety of conditions. The antibiotic resistance of the transfected cells was similar to that of control cells, suggesting that the presence of HMG did not affect the expression of actively transcribed genes. However, examination of the protein profile on two-dimensional polyacrylamide gel electrophoresis revealed differences between control and HMG-transfected cells. PMID- 2226653 TI - Fibronectin and collagen gene expression during in vitro ageing of pig skin fibroblasts. AB - The fibronectin, collagen type I, and collagen type III genes code for three major proteins of the cell matrix. The age-related alterations in their expression were measured during the in vitro lifespan of pig skin fibroblasts. We observed changes in the transcription rate of these specific genes during ageing. The levels of fibronectin and type III collagen mRNA rose markedly during the senescence phase. The level of collagen type I mRNA decreased during cell ageing, while that of beta-actin did not change. As regards proteins, we observed a sharp increase in the secreted noncollagenous proteins and in the total proteins of the cell layer during senescence. On the contrary, the secretion of the collagenous proteins decreased during senescence. Moreover, most of the newly synthesized molecules of collagen were immediately degraded in the cells, before their extracellular secretion. The terminal phenotype of pig senescent cells was therefore characterized by overexpression of fibronectin and type III collagen genes and reduced expression of the type I collagen gene. Surprisingly, for fibronectin and type III collagen, that terminal phenotype resembled the one normally found in the fibroblasts during the processes of tissue repair, cicatrization, and development. PMID- 2226654 TI - Agents which modify colonial morphology of tumor cells also affect acid vesicle function and fibronectin deposition in the extracellular matrix. AB - The tumor cell line U937A is motile, weakly plastic-adherent and forms large, loosely packed colonies in vitro and is invasive and metastatic in vivo. U937A/R, a mutant selected for resistance to killing by tumor necrosis factor (TNF), is less motile, more adherent and forms small, tightly packed colonies and is not invasive or metastatic. U937A and U937A/R also have differing cytoplasmic distributions of acid vesicles, and unlike U937A, U937A/R fails to deposit fibronectin into its extracellular matrix. In this study we have sought reagents that could convert "loose" U937A cells into the nonmetastatic, "tight" colonial phenotype. Six effective reagents were found: wheat germ agglutinin, phytohemagglutinin-L, dexamethasone, chloroquine, promethazine, and monensin. All 6 reagents caused swelling and/or redistribution of acid vesicles but phytohemagglutinin-L, dexamethasone, and monensin also reduced fibronectin deposition in the extracellular matrix. Therefore, these agents probably reduce motility by interference with recycling of cell surface receptors through acid vesicles and also in some cases by altering the extracellular matrix. PMID- 2226655 TI - Fibroblast behavior on gels of type I, III, and IV human placental collagens. AB - Various collagens were extracted and purified from human placenta after partial pepsin digestion. We prepared type III + I (57:43), enriched type I, type III, and type IV collagens on an industrial level, and studied their biological properties with MRC5 fibroblast cells. Using the process of contraction of a hydrated collagen lattice described by Bell, we found tha the contraction rate was dependent on collagen type composition. The contraction was faster and more pronounced with pepsinized type I collagen than with pepsinized type III + I (57:43) collagen; the lowest rate was obtained with the pepsinized type III collagen. Using a new technique of collagen cross-linking, a gel was made with type IV collagen. This cross-linking procedure, based on partial oxidation of sugar residues and hydroxylysine by periodic acid, followed by neutralization, resulted in an increased number of natural cross-link bridges between oxidized and nonoxidized collagen molecules, without internal toxic residues. The fibroblasts were unable to contract type IV/IVox collagen gels. The type IV/IVox collagen gel was transparent and its amorphous ultrastructure lacked any visible striated fibrils. Fibroblast cells exhibited atypical behavior in these type IV/IVox collagen gels as evidenced by optical and electron microscopy. The penetration of fibroblasts could be measured. Fibroblasts penetrated faster in type IV/IVox collagen gels than in untreated type III + I collagen gels. The lowest rate of penetration was obtained with cross-linked type III + I gels. Fibroblast proliferation was similar on untreated or cross-linked type III + I collagen gels and slightly increased on type IV/IVox collagen gels, suggesting that this cross-linking procedure was not toxic. PMID- 2226656 TI - Nathan Shock 1906-1989. PMID- 2226657 TI - Cellular activity, matrix proteins, and aging bone. AB - The extracellular matrix of bone is composed of proteins from both local and exogenous sources. Many of these are known growth factors (e.g., transforming growth factors-beta; insulin-like growth factors; and fibroblast growth factors) which concentrate in mineralized bone and probably contribute to the ability of bone to regenerate itself on injury. With advancing age, human osteoblasts have reduced bone formative properties and in vitro, osteoblasts from fetuses generally have greatly increased proliferative and biosynthetic capacities compared to cells from adult donors. Aside from type I collagen, many noncollagen components are synthesized by osteoblasts and secreted to the bone matrix space. Several of these are cell attachment proteins (e.g., fibronectin, thrombospondin, osteopontin) which greatly influence cytodevelopment and differentiation. They are degraded to lower molecular weight fragments with advancing age, probably deactivating their true bioactivities. It is not know whether the age-related degradation of these proteins affects bone cell function in aged individuals. Several of the bone matrix proteins are also found in platelets and have been implicated in the wound-repair process. One of these, osteonectin, is found in a wide variety of nonbone cell systems, but only in periods of rapid growth and proliferation. Osteonectin production is the highest and is maintained the longest in bone compared to all other tissues of the body. Thus, reduced osteonectin production in aged bone cells may be an important parameter for further study. PMID- 2226658 TI - 1,25-Dihydroxyvitamin D3 increases the toxicity of hydrogen peroxide: the role of calcium and heat shock. AB - 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] increases synthesis of heat shock proteins in monocytes and U937 cells and protects these cells from thermal injury. We therefore examined whether 1,25-(OH)2D3 would also modulate the susceptibility to H2O2-induced oxidative stress. Prior incubation for 24 h with 1,25-(OH)2D3 (25 pM or higher) produced unexpected increased H2O2 toxicity. Since cellular Ca2+ may be a mediator of cell injury, we investigated the effects of altering extracellular Ca2+ ([Ca2+]e) on 1,25-(OH)2D3-enhanced H2O2 toxicity, as well as the effects of 1,25-(OH)2D3 and H2O2 on cytosolic-free Ca2+ concentration ([Ca2+]f). Basal [Ca2+]f in medium containing 1.5 mM Ca2+ as determined by fura-2 fluorescence was higher in 1,25-(OH)2D3-pretreated cells than control cells (137 versus 112 nM, p less than 0.005). H2O2 induced a rapid increase in [Ca2+]f (to greater than 300 nM) in both 1,25-(OH)2D3-treated and control cells, which was prevented by a reduction in [Ca2+]e to less than basal [Ca2+]f. The 1,25-(OH)2D3 induced increase in H2O2 toxicity was also prevented by preincubation with 1,25 (OH)2D3 in Ca2(+)-free medium or by exposing the cells to H2O2 in the presence of EGTA. Preexposure of cells to 45 degrees C for 20 min, 4 h earlier, partially prevented the toxic effects of H2O2 particularly in 1,25-(OH)2D3-treated cells, even in the presence of physiological levels of [Ca2+]e. Thus, 1,25-(OH)2D3 potentiates H2O2-induced injury probably by increasing cellular Ca2+ stores. The protective effects of heat shock are probably exerted at a site distal to the toxic effects of Ca2+. The 1,25-(OH)2D3-induced amplification of the heat shock response likely represents a mechanism for counteracting the Ca2(+)-associated enhanced susceptibility of oxidative injury due to 1,25-(OH)2D3. PMID- 2226659 TI - Calcium antagonists and intimal cell proliferation in atherogenesis. AB - Smooth muscle cell (SMC) migration and intimal proliferation are major events in the formation of the atherosclerotic lesions. Among other processes, calcium may participate in atherogenesis by affecting SMC proliferation. Calcium antagonists, which possess antiatherosclerotic properties in animal models, are effective in inhibiting SMC proliferation. This effect has been demonstrated both in vitro in cell culture and in vivo in balloon-catheterised rats and rabbits. Such an effect, indicates a possible mechanism involved in the antiatherosclerotic activity elicited by this category of drugs. PMID- 2226660 TI - Cardiac aging, calcium overload, and arrhythmias. AB - The effect of aging was tested on experimental ventricular arrhythmias in isolated heart preparations from normal Wistar rats (NWR), Wistar Kyoto rats (WKY), and spontaneously hypertensive rats (SHR). Delayed afterdepolarizations and triggered activity induced by high-calcium perfusion (16 mM) in isolated papillary muscles were more frequent in the 24-month-old than in 6-month-old NWR. Reperfusion-VA were more severe in 14-month-old SHR than in WKY. The authors have previously shown that: (1) reperfusion- and reoxygenation-induced VA, in the isolated Langendorff perfused heart, were significantly more severe and frequent in 24-month-old than in 6-month-old NWR; (2) no age-related difference in the incidence of programmed electrical stimulation (PES, train of stimuli + 1 or 2 extrastimuli)-induced VA was observed in isolated NWR hearts during control perfusion, after coronary artery ligation or during hypoxia; (3) on the contrary, the incidence of PES-induced VA was significantly higher in isolated hearts from 14-month-old SHR than from 3-month-old SHR, and 3-month-old and 14-month-old WKY. It was concluded that "physiological" aging is associated with a higher propensity to calcium-related VA, while "pathological" aging characterized by hypertension of long duration increases the incidence of PES-induced VA, probably caused by myocardial fibrosis, which could facilitate reentry. PMID- 2226661 TI - Parathyroid origin of a new hypertensive factor. AB - Many physiological abnormalities have been described in essential hypertension, yet the cause of this condition remains unknown. Included among the reported abnormalities are alterations in serum and tissue calcium levels, abnormalities in calcium regulating hormones, and the involvement of the parathyroid gland in some forms of hypertension. In the current study, the authors review evidence suggesting that a newly described hypertensive factor may explain a number of these abnormalities. This factor was first described in spontaneously hypertensive rat (SHR) plasma and is characterized by its ability to raise blood pressure in a delayed manner in normotensive rats, as well as by its ability to increase calcium uptake in vascular smooth muscle. The factor seems to be produced by the parathyroid gland, yet it is distinct from parathyroid hormone. Histological studies suggest that the factor may be produced by a specific cell type in the parathyroid glands. Given the parathyroid gland dependency of this factor, the authors have tentatively named it "parathyroid hypertensive factor," or "PHF." PMID- 2226662 TI - Red cell aging and active calcium transport. AB - The authors have investigated the relationships between the active calcium transport across the human red blood cell (RBC) membrane and the RBC aging processes in vivo and in vitro. For the study of this biological system, the authors have determined the active calcium uptake by inside-out membrane vesicles obtained from selected RBC populations. This model provided an optimal way to assess the biochemical and functional responses of the human cell to the oxidative stimulus triggered by the cellular aging processes. The activity of the calcium pump is indeed strictly correlated to the oxidative damage suffered by the RBC, being higher in the aged RBC. It appears that the main controller of the active calcium transport is the age-dependent protein inhibitor of the calcium pump. PMID- 2226663 TI - Bone loss and age-related fractures. AB - The aging of the skeleton represents an important cause of both morbidity and mortality in the Western World. A great deal is known about the epidemiology, pathogenesis, and structural alterations which occur during the osteoporotic process to increase the risk of fracture with age. Whereas osteoporosis is associated with a decrease in bone mass, factors other than bone mass are clearly important. These include the turnover of bone and the destruction of trabecular elements, the repair of fatigue damage, as well as extraskeletal factors. An improved understanding of the aging of bones will form a basis for improved strategies for its prevention and treatment. PMID- 2226664 TI - Non-invasive methods for quantitating bone loss of aging. AB - The clinical utility of bone mass measurements has been the subject of considerable debate. The determination of whether a measurement has utility in clinical practice is difficult, but several elements must be present. First, the measurement must be predictive of clinical outcomes. Two recent studies have shown that bone mass measurements predict the incidence of both nonspine and vertebral body fractures. A second necessary element is the availability of therapeutic options which would be based on these measurements. The effectiveness of estrogen replacement therapy in preventing bone loss and subsequent fractures is well documented. It is also possible that alterations in glucocorticoid therapy or treatment of hyperparathyroidism might be based on bone measurements. Finally, it should be clear that the information available through bone mass measurements would not be otherwise obtainable. Researchers have yet to demonstrate that other risk fractures are adequate substitutes either in the prediction of bone mass or in the estimations of fracture risk. Although it is not yet clear that bone mass measurements should be used in screening, their clinical utility in specific circumstances is becoming established. PMID- 2226665 TI - Vertebral bone loss in menopause. AB - A direct correlation between loss of ovarian function and reduction of bone mass is well established. The incidence of fractures sharply increases with age starting from the menopause. Therefore, it is very important to know the rate of bone loss occurring after menopause, at both trabecular and cortical levels. Several factors may contribute to the reduction of bone mass in menopause. Reduced estrogen secretion results in reduced intestinal calcium absorption, increased bone resorption, and probably a deficient production of calcitonin. Furthermore, in vivo and in vitro experimental data confirm that estrogen failure is associated with histologic changes, mirroring the biochemical changes described in postmenopausal osteoporosis. PMID- 2226666 TI - The role of interleukin-1 in postmenopausal bone loss. AB - Interleukin-1 (IL-1), a cytokine best known for its ability to stimulate lymphocyte proliferation, has recently been shown to stimulate bone resorption and modulate bone formation in vivo. Consequently, the authors have devised a series of studies to investigate the relationship between bone remodeling, menopause, and monocyte IL-1-secretion. In a first study, monocytes from osteoporotic patients were found to produce more IL-1 than monocytes from control subjects. IL-1 activity was also found to reflect histomorphometric indices of bone formation, but not of bone resorption. In a second study, devised to assess the effect of menopause on the relationship between IL-1 and bone turnover, a significant correlation was found between IL-1 and BGP in premenopausal osteoporotic women and osteoporotic men, but not in both postmenopausal osteoporotic subjects and normal subjects of either sex. In a third study, IL-1 from untreated postmenopausal women was found to be higher than in either untreated premenopausal or estrogen/progesterone-treated postmenopausal women. A significant negative correlation was found between IL-1 and years since menopause in both the healthy and osteoporotic postmenopausal women. Premenopausal IL-1 levels were achieved within eight years of menopause in the healthy but not in the osteoporotic subjects. In osteoporotic women, high IL-1 levels were evident as long as 15 years after menopause. IL-1 also correlated inversely with mineral density as measured by quantitative computer tomography. In prospective study, treatment with estrogen/progesterone caused a significant increase in IL-1 activity. This data indicates that monocyte IL-1 production mirrors the rate of bone turnover in both the healthy and osteoporotic patient, and that alteration in IL-1 production may underlie the postmenopausal acceleration of bone loss and its inhibition by ovarian steroids. PMID- 2226667 TI - Biological effects of aging on bone and the central nervous system. AB - The skeletal and nervous systems express conspicuous signs of aging in humans in the form of osteoporosis and senile dementia, the most common diseases affecting the elderly population. Although the prevalence of these diseases progressively rises with advancing age, especially in females, the interrelationship between the degenerative changes of the skeletal and nervous systems has not been studied in detail. Defective 1,25(OH)2D synthesis in chronic renal failure is known to cause renal osteodystrophy and is also associated with the appearance of dialysis encephalopathy and a decrease of the conduction velocity of peripheral nerves. Calcium content of the nervous system is increased in this condition, suggesting the existence of generalized abnormalities of calcium metabolism, which affect both the skeletal and nervous system. The mild, chronic renal failure of aging, and the consequent secondary hyperparathyroidism, might therefore contribute to the development of nervous degenerative diseases. PMID- 2226668 TI - Calciotropic hormones and the aging bone. AB - The aging of bone is conditioned by intrinsic and extrinsic factors. The decrease of bone density, of cortical and of trabecular bone volume with age goes along with an increase of interstitial trabecular bone (Courpron, 1981), in addition to other intrinsic structural changes. Interstitial bone has a lower cellularity and a lower metabolic activity than the bone tissue which is closer to the trabecular surface. This increase of interstitial bone serves as an example for the supposed decrease of bone cellularity, cellular activity, and hormonal receptors with age in bone. Therefore, the "playground" for calciotropic hormones is reduced in advanced age, independently from the hormonal changes which will be discussed thereafter. The relative role of this decrease of the target organ with age is not yet fully understood. The process of aging can interfere with each step of calcium metabolism from calcium intake and absorption, vitamin D intake and absorption to vitamin D production, hydrolysation and action, as well as to secretion and action of calciotropic hormones such as PTH, calcitonine, and gonadal steroids. PMID- 2226669 TI - Biological activity of calcitonin and its assessment. AB - Radioimmunoassay has been the method of choice for the routine determination of calcitonin (CT) in biological fluids, mainly due to its precision, sensitivity, and ability to handle large numbers of samples. However, spuriously high results are often obtained due to undefined cross-reactivities of polyclonal antisera to precursors, polymers, metabolites, or fragments of CT, or to other physiological and pathological variants of the hormone. In routine practice, radioimmunoassays of CT are being replaced by immunometric two-site 'sandwich' assays utilizing monoclonal antibodies against defined antigenic epitopes. Hormone activity is, however, accurately quantifiable by biological assays based on the exquisite hormonal sensitivity of isolated osteoclasts. The assays are highly specific and remarkably sensitive. Their use in routine laboratories is nevertheless limited only to specific situations. PMID- 2226670 TI - Calcitonin and postmenopausal bone loss. AB - In order to establish the role of calcitonin (CT) in postmenopausal bone loss, we studied CT metabolism in 25 pre- and postmenopausal women. Postmenopausal women presented a highly significant reduction of CT basal levels compared to premenopausal females (p less than 0.01). Also, production rates of CT in osteoporotics were significantly lower than in either young premenopausal (18-25 years old), older premenopausal (35-40 years old), or postmenopausal healthy subjects. In a study in rabbits, we found that injection of CT, along with equimolar amounts of anti-SCT antibodies extracted from serum of pagetic patients, did not inhibit the hypocalcemic response to the hormone, thus demonstrating that resistance to CT treatment cannot be accounted for by antibody production. In a subsequent clinical study in patients with Paget's disease of bone, we found that 200 IU/day of salmon CT (SCT), given by nasal spray, improved both clinically and biochemically the activity of the disease, as demonstrated by 37 +/- 4% decrease of serum alkaline phosphatase and 35 +/- 5% fall of urinary excretion of hydroxyproline after six months of therapy. The effectiveness of CT as nasal spray was further tested in healthy women at an early stage of menopause. A 12-month course of intranasal SCT counteracted early postmenopausal bone loss, presumably by inhibiting bone resorption. In conclusion, intranasal CT seems to be a very attractive alternative to be considered for the prevention of postmenopausal osteoporosis. PMID- 2226671 TI - The concept and treatment of osteoporosis. AB - Osteoporosis is a dynamic process, thought to be caused by an uncoupling between osteoblast and osteoclast activity. Altered pulsatile secretion of growth hormone and parathyroid hormone (PTH) have been proposed as pathogenetic factors for this unbalanced coupling. The anatomical lesions are believed to be reversible until trabecular perforations develop, if fractures already occurred the anatomical defect is permanent. It is helpful to classify osteoporosis in stages of increasing severity depending on bone density and the presence of fractures. Theoretically, if the bone density is above the fracture threshold, then the only therapeutic goal is to maintain the bone mass. If instead the mineral density is below the threshold, an active therapy is needed with drugs that can possibly increase the skeletal mass. Osteoporosis with multiple fractures cannot be reversed. The authors propose a promising pharmacologic treatment for osteoporosis, based on the combination of human PTH-(1-38) and intranasal salmon calcitonin. If started in the early stages of the osteoporotic process, this regimen may restore the initial bone mass. In more advanced stages, only a correction of the metabolic defect is possible, but the irreversible vertebral deformities are not affected. On the basis of the results, cyclic therapy with human PTH-(1-38) and salmon calcitonin represents a good treatment choice for osteoporosis. PMID- 2226672 TI - Receptor sites involved in the action of calcium blocking agents. AB - The affinities of calcium blocking agents (CBAs) for membrane binding sites and for calmodulin were compared to their potencies at inhibiting contraction of various isolated arteries. Two allosterically linked binding sites, the dihydropyridine (DHPS) and benzothiazepine-phenylakylamine (BS) one, were characterized. In spite of a correlation between the affinities of a number of hydrophobic CBAs and calmodulin antagonists for DHPS and for calmodulin, these drugs displayed higher affinities for BS. Furthermore, their potency at inhibiting calcium-induced contraction in depolarized rat aorta rings was correlated to their affinity for the latter site. These results suggest that binding to membrane sites was the basis of the inhibition of depolarization elicited contraction by all CBAs, including calmodulin antagonists. Differences in sensitivity to CBAs depending on the artery and whether they were depolarized or stimulated by noradrenaline were shown in further experiments on rat cerebral artery and resistance arterioles. These differences in sensitivity did not correspond to differences in the apparent affinity of the drugs. This suggests that the receptors of CBAs (and therefore the associated calcium channels) involved in the responses to depolarization and to the agonist were identical. PMID- 2226673 TI - Factors influencing the responses to calcium antagonists in elderly patients with hypertension and ischaemic heart disease. AB - The results of a variety of studies that have investigated the effect of age on the pharmacokinetics and pharmacodynamics of calcium antagonist drugs have produced the following conclusions. Primarily, as a result of an age-dependent decline in plasma drug clearance, there is a tendency for elderly patients to have higher plasma drug concentrations than young patients. In terms of pharmacological response, there is good evidence of therapeutic efficacy in both hypertension and ischaemic heart disease, but there is no convincing evidence of any preferential age-related effect, particularly in relation to blood pressure reduction. Similarly and conversely, there is no convincing evidence that the elderly are at greater risk from the adverse effects of calcium antagonist drugs, particularly those which reflect the negative effects on cardiac conduction. An integrated mathematical method for describing antihypertensive response, which incorporates both pharmacokinetic and pharmacodynamic information, has been used to investigate the variability in antihypertensive effect with nifedipine and verapamil. There was no relationship between responsiveness (in mmHg/ng/mL) and patient age and plasma renin activity; however, responsiveness during chronic treatment was directly correlated with the height of the starting blood pressure and the response to the first dose. PMID- 2226674 TI - Adenosine system and cell calcium translocation: interference of calcium channel blockers. AB - Adenosine is able to inhibit in vitro neutrophil functions induced by formyl methionyl-leucyl-phenylalanine (FMLP) and A23187, but not phorbol 12-myristate 13 acetate (PMA). The inhibiting activity on A23187 is reversed by increasing extracellular Ca2++ concentration. The calcium entry blocker flunarizine shows an activity very similar to that of adenosine. Both adenosine and flunarizine prevent Ca++ influx into activated neutrophils as detected by the fluorescent Ca++ chelator Quin-2. Finally, flunarizine binds to the neutrophil membrane and adenosine competitively inhibits flunarizine binding as assessed by 1H-Nuclear Magnetic Resonance (1H-NMR) technique, thus indicating that the two agents share a common binding site on the cell membrane. PMID- 2226675 TI - Smoking, calcium, calcium antagonists, and aging. AB - Aging is characterized, besides other changes, by a progressive increase in calcium content in the arterial wall, which is enhanced by diabetes mellitus, osteoporosis, arterial hypertension, and tabagism. As to tabagism, experiments in animals have shown that nicotine can increase calcium content of the arterial wall, and clinical studies have demonstrated that cigarette smoking induces peripheral vasoconstriction, with consequent increase in blood pressure levels. In order to study the role of calcium ions in the pathogenesis of the vasoconstrictive lesions caused by "acute" smoking, the author has studied the peripheral vascular effects of the calcium-channel antagonist nifedipine, a dihydropyridine derivative, and calcitonin, a hypocalcemizing hormone which possess vasoactive actions on 12 elderly regular smokers (mean age 65.8 years). The results demonstrated that both nifedipine (10 mg sublingually 20 min before smoking) and salmon calcitonin (100 MRC U/daily intramuscularly for three days) are able to prevent peripheral vasoconstriction evaluated by Doppler velocimetry, as well as the increase of blood pressure induced by smoking. On the basis of our results, the author proposes that cigarette smoking-induced vasoconstriction is a calcium-mediated process, which can be hindered by drugs with calcium antagonist action. PMID- 2226676 TI - 1,25-Dihydroxyvitamin D3 enhances cytosolic free calcium in HL-60 cells. AB - 1,25-Dihydroxyvitamin D3 (1,25[OH]2D3) caused a rise in the concentration of intracellular free calcium ions ([Ca2+]i) in HL-60 cells. This effect of 1,25(OH)2D3 parallels its suppression of cell proliferation and its induction of cell differentiation into monocyte-like cells. The changes in [Ca2+]i are dose and time dependent. The concentration of 1,25(OH)2D3 (10(-7) M) that induced maximal differentiation also caused the maximal increase in intracellular Ca2+. The rise in cytoplasmic free Ca2+ concentration was not immediate and reached statistical significance only after 24 h. The [Ca2+]i reached its peak at 48 h (134 +/- 4 nM vs 101 +/- 3 nM in controls) and remained stable at this level. The increase in intracellular Ca2+ was found to be related to new protein synthesis, because it was inhibited in the presence of specific RNA and protein synthesis inhibitors. The rise in [Ca2+]i was not observed during incubation of HL-60 cells with 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), a vitamin D metabolite that does not induce the differentiation of HL-60 cells. In contrast, 25-hydroxyvitamin D3 (25-OH-D3) and phorbol 12-myristate 13-acetate (TPA), both of which induce differentiation in this cell line, also increase [Ca2+]i. In conclusion, the present study emphasizes that a significant increase in intracellular free Ca2+ occurs in the effect of 1,25(OH)2D3 on HL-60 cells. PMID- 2226677 TI - Evidence for the existence of circulating monoclonal B-lymphocytes in multiple myeloma patients. AB - Multiple myeloma is characterized by the proliferation of a single clone of plasma cells producing a homogeneous immunoglobulin fraction. In this disease, plasma cells home essentially in the bone marrow. However, controversy exists whether peripheral blood B-lymphocytes in patients with multiple myeloma (MM) are part of the malignant clone. We investigated clonal immunoglobulin gene rearrangement (IgGR) in T-cell-depleted peripheral blood mononuclear cells as well as in bone marrow of these patients. Seven out of 17 MM patients demonstrated an identical IgGR in bone marrow and peripheral mononuclear cells, these patients were in an active stage of the disease. In nine patients in plateau phase, clonal IgGR could not be detected in peripheral blood. Peripheral mononuclear cells from ten patients with monoclonal gammopathies of undetermined significance (MGUS) were also examined and no IgGR was detected. The existence of monoclonal B-lymphocytes in the circulation of patients with MM suggests a mechanism whereby the malignant clone homes in the bone marrow through peripheral blood. These findings may also be used for the evaluation of patients with active myeloma and the determination of plateau phase. PMID- 2226678 TI - Effects of mixed chimeric bone marrow repopulation on platelet storage pool associated bleeding defects in mouse mutants. AB - We have previously shown mouse platelet storage pool deficiency (SPD) to be associated with lesions at eight different genetic loci, each of which is sufficient to produce murine SPD. We have also shown that normal bleeding times and normal platelet functions are restored when mice with SPD are transplanted with marrow from normal mice. Conversely, when normal mice are transplanted with mutant marrow, they present symptoms of SPD. In order to determine the amount of normal platelets needed to prevent the prolonged bleeding times associated with SPD, we established stable mixed chimeric mice by transplanting various ratios of normal and mutant marrow into lethally irradiated host animals. The proportion of normal input marrow correlated well with the proportion of normal peripheral red blood cells and platelets determined in chimerae 100 days after transplantation using direct morphology and electrophoretic variants of glucose phosphate isomerase to identify normal and mutant cell populations. The proportions of normal input marrow were also reflected in the proportions of platelets with normal and mutant platelet morphology in the chimerae. This confirms that the platelet abnormality in SPD is intrinsic to the stem cell population from which the platelets are derived. When bleeding times were determined in the mixed chimeric mice, a surprisingly high percentage of normal platelets (greater than 50% and sometimes greater than 75%) were needed to stop bleeding. These results suggest that the mutant platelets in the mixed chimeric mice may interfere with normal platelet aggregation patterns. They also raise some important considerations in devising treatment for SPD. Bleeding episodes in human SPD are normally treated by platelet transfusion. The results suggest that, at least in some cases, transfusions may not be effective. Also, in future gene therapy of this disease, it is like that a functional gene will have to be present in greater than 50% of stem cells for therapy to be effective. PMID- 2226679 TI - Modulation of etoposide (VP-16) cytotoxicity by verapamil or cyclosporine in multidrug-resistant human leukemic cell lines and normal bone marrow. AB - We studied the effects of two modulators of multidrug resistance (MDR), cyclosporine and verapamil, on the cytotoxicity of etoposide (VP-16) in normal human bone marrow; two human leukemia cell lines, K562 and CEM; their MDR variants, K562/DOX and CEM/VLB; and mixtures of normal marrow and leukemic cells. VP-16 was selectivity toxic to the parental leukemic cells, with IC-50 values of 2 microM for CEM cells, 1.5 microM for K562 cells, and 12 microM for normal marrow CFU-GM. This selectivity was lost in the MDR variant leukemia cells, with IC-50s of 20 microM in K562/DOX and 8 microMs in CEM/VLB. Cyclosporine, 6 microMs, and verapamil, 20 microM, alone were nontoxic to bone marrow CFU-GM, and did not significantly increase the toxicity of VP-16 to normal marrow cells or to the two drug-sensitive leukemic cell lines. However, cyclosporine specifically enhanced the cytotoxicity of VP-16 in the MDR leukemia cells, reducing the IC-50 to the same level as the parental sensitive cells. Verapamil was considerably less effective. In a mixing experiment that included K562/DOX cells and normal bone marrow, cyclosporine increased the toxicity of VP-16 to the resistant leukemic cells by nearly 20-fold. Because the cytotoxic effect of cyclosporine is additive for resistant tumor cells, its combination with VP-16 may be useful in the purging of contaminating tumor cells prior to autologous bone marrow transplantation. PMID- 2226680 TI - High-dose recombinant human erythropoietin for treatment of anemia in myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria: a pilot study. AB - In a dose escalation study we tested the feasibility and tolerance of high-dose recombinant human erythropoietin (r-HuEPO) therapy in four patients with ineffective erythropoiesis due to myelodysplastic syndromes (MDS) or paroxysmal nocturnal hemoglobinuria (PNH). Recombinant human EPO was administered i.v. with an initial dose of 50 U/kg body weight (BW) three times per week. The dose was increased by steps of 25 or 50 U/kg bW with intervals of 1-4 weeks up to a maximum dose of 500 U/kg BW three times per week. All patients were treated as outpatients. Pre-study treatment with cyclosporin A and/or Danazol was continued in three patients. In one patient r-HuEPO was discontinued after 20 weeks because of relapse of severe aplastic anemia. No major side effects were observed even at the maximum dose. One patient with PNH showed an increase of hemoglobin from 89 to 139 g/liter that permitted monthly phlebotomies to reduce his iron overload. In one patient with MDS the reticulocyte count increased from 2.5 to 50 x 10(9)/liter, and the transfusion requirement decreased to 2 U every 3-4 weeks instead of every 2 weeks. Two patients did not complete the whole treatment period and showed no rise in reticulocyte count. We conclude that high dose r HuEPO therapy is feasible in patients with anemia due to MDS or PNH. High-dose r HuEPO appears to have some effect on anemia due to ineffective erythropoiesis in a subgroup of patients. Further studies are needed to identify potential responders and to define the optimal administration of r-HuEPO. PMID- 2226681 TI - Integration in descending motor pathways controlling the forelimb in the cat. 17. Axonal projection and termination of C3-C4 propriospinal neurones in the C6-Th1 segments. AB - Collateralization and termination of single C3-C4 propriospinal neurones (PNs) have been studied in the C6-Th1 segments of the cat using two methods: threshold mapping for antidromic activation of C3-C4 PNs and intra-axonal injection of horseradish peroxidase. Low threshold points for antidromic activation of C3-C4 PNs were found in the region of different motor nuclei in lamina IX both at one level and at different segmental levels, in all parts of lamina VII, in the lateral part of lamina VI and in the dorsal and ventral parts of lamina VIII. Collaterals were found from C6 to Th1. A marked decrease of conduction velocity of the stem axon occurred in the caudal region of termination, while it was almost constant in the rostral region of termination. HRP was injected iontophoretically in C6-Th1 into stem axons of neurones, which were activated antidromically from the ventral part of the lateral funiculus in C5/C6, from the lateral reticular nucleus (LRN) and monosynaptically from the corticospinal fibres (stimulated in the contralateral pyramid) which were transected in C5/C6. Reconstruction of successfully stained stem axons, revealed collaterals with terminals on presumed motoneurones in different parts of lamina IX and on interneurones in laminae IV-VIII. These findings confirm previous results which showed monosynaptic projections from C3-C4 PNs to forelimb motoneurones and Ia inhibitory interneurones. With respect to termination in the region of the motoneurones in lamina IX and in the region of Ia inhibitory interneurones in lamina VII, three patterns were found: 1) termination mainly in lamina IX (n = 1) 2) termination in laminae IX and VII (n = 15) and 3) termination mainly in lamina VII (n = 2). However, in some cases the same stem axon gave off collaterals which terminated either on motoneurones in lamina IX or on presumed Ia inhibitory interneurones in lamina VII. Furthermore, when the stem axons had collaterals which terminated in different motor nuclei only some of these collaterals had additional terminations on presumed Ia inhibitory interneurones. This result suggest that C3-C4 PNs do not follow a strict Ia pattern of reciprocal innervation. It is tentatively proposed that the difference of innervation may be related to the type of multi-joint movement, such as target-reaching with the forelimb, which has been shown to be controlled by the C3-C4 PNs. Termination in laminae VI, VIII and different parts of lamina VII indicates that C3-C4 PNs also project to other types of neurones than motoneurones and Ia inhibitory interneurones.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2226683 TI - The human horizontal vestibulo-ocular reflex in response to high-acceleration stimulation before and after unilateral vestibular neurectomy. AB - The normal horizontal vestibulo-ocular reflex (HVOR) is largely generated by simultaneous stimulation of the two horizontal semicircular canals (HSCCs). To determine the dynamics of the HVOR when it is generated by only one HSCC, compensatory eye movements in response to a novel vestibular stimulus were measured using magnetic search coils. The vestibular stimulus consisted of low amplitude, high-acceleration, passive, unpredictable, horizontal rotations of the head with respect to the trunk. While these so called head "impuses" had amplitudes of only 15-20 degrees with peak velocities up to 250 deg/s, they had peak accelerations up to 3000 deg/s/s. Fourteen humans were studied in this way before and after therapeutic unilateral vestibular neurectomy; 10 were studied 1 week or 1 year afterwards; 4 were studied 1 week and 1 year afterwards. The results from these 14 patients were compared with the results from 30 normal control subjects and with the results from one subject with absent vestibular function following bilateral vestibular neurectomy. Compensatory eye rotation in normal subjects closely mirrored head rotation. In contrast there was no compensatory eye rotation in the first 170 ms after the onset of head rotation in the subject without vestibular function. Before unilateral vestibular neurectomy all the patients' eye movement responses were within the normal control range. One week after unilateral vestibular neurectomy however there was a asymmetrical bilateral HVOR deficit. The asymmetry was much more profound than has been shown in any previous studies. The HVOR generated in response to head impulses directed away from the intact side largely by ampullofugal disfacilitation from the single intact HSCC (ignoring for the moment the small contribution to the HVOR from stimulation of the vertical SCCs), was severely deficient with an average gain (eye velocity/head velocity) of 0.25 at 122.5 deg/sec head velocity (normal gain = 0.94 +/- 0.08). In contrast the HVOR generated in response to head impulses directed toward the intact side, largely by ampullopetal excitation from the single intact HSCC, was only mildly (but nonetheless significantly) deficient, with an average gain of 0.80 at 122.5 deg/sec head velocity. At these accelerations there was no significant improvement in the average HVOR velocity gain in either direction over the following year. These results indicate that ampullopetal excitation from one HSCC can, even in the absence of ampullofugal disfacilitation from the opposite HSCC, generate a near normal HVOR in response to high-acceleration stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2226682 TI - Spatial properties of second-order vestibulo-ocular relay neurons in the alert cat. AB - Second-order vestibular nucleus neurons which were antidromically activated from the region of the oculomotor nucleus (second-order vestibuloocular relay neurons) were studied in alert cats during whole-body rotations in many horizontal and vertical planes. Sinusoidal rotation elicited sinusoidal modulation of firing rates except during rotation in a clearly defined null plane. Response gain (spike/s/deg/s) varied as a cosine function of the orientation of the cat with respect to a horizontal rotation axis, and phases were near that of head velocity, suggesting linear summation of canal inputs. A maximum activation direction (MAD) was calculated for each cell to represent the axis of rotation in three-dimensional space for which the cell responded maximally. Second-order vestibuloocular neurons divided into 3 non-overlapping populations of MADs, indicating primary canal input from either anterior, posterior or horizontal semicircular canal (AC, PC, HC cells). 80/84 neurons received primary canal input from ipsilateral vertical canals. Of these, at least 6 received input from more than one vertical canal, suggested by MAD azimuths which were sufficiently misaligned with their primary canal. In addition, 21/80 received convergent input from a horizontal canal, with about equal number of type I and type II yaw responses. 4/84 neurons were HC cells; all of them received convergent input from at least one vertical canal. Activity of many vertical second-order vestibuloocular neurons was also related to vertical and/or horizontal eye position. All AC and PC cells that had vertical eye position sensitivity had upward and downward on-directions, respectively. A number of PC cells had MADs centered around the MAD of the superior oblique muscle, and 2/3 AC cells recorded in the superior vestibular nucleus had MADs near that of the inferior oblique. Thus, signals with spatial properties appropriate to activate oblique eye muscles are present at the second-order vestibular neuron level. In contrast, none of the second-order vestibuloocular neurons had MADs near those of the superior or inferior rectus muscles. Signals appropriate to activate these eye muscles might be produced by combining signals from ipsilateral and contralateral AC neurons (for superior rectus) or PC neurons (for inferior rectus). Alternatively, less direct pathways such as those involving third or higher order vestibular or interstitial nucleus of Cajal neurons might play a crucial role in the spatial transformations between semicircular canals and vertical rectus eye muscles. PMID- 2226684 TI - New method to identify nociceptor units innervating glabrous skin of the human hand. AB - A new technique is described for detecting nociceptor activity in microelectrode recordings from cutaneous fascicles of the human median nerve. The search strategy involves combined intraneural microstimulation and microneurographic recording in intrafascicular sites, where a critically low electrical stimulus amplitude evokes a threshold sensation of pain. From the subject's projection of pain to a small area of skin, the experimenter is guided to receptive fields of recordable nociceptor units. This technique has allowed, for the first time, to identify and study receptive properties of very high threshold nociceptors with A and C fibers in the glabrous skin of the human hand. PMID- 2226685 TI - GABAergic mechanisms in the cat red nucleus: effects of intracerebral microinjections of muscimol or bicuculline on a conditioned motor task. AB - Interneurons in the Red Nucleus (RN) are known to be under cortical control and to exert an inhibitory action, mediated by GABAergic mechanisms, on the main output towards the spinal cord. The effects of discrete injections of a GABA receptor agonist (muscimol) or an antagonist (bicuculline) in the Red Nucleus were tested on a motor task performed by seven cats. The subjects were trained to release a lever with a flexion movement of the forelimb controlled by a reaction time (RT) paradigm. Muscimol as well as bicuculline increased RTs in a dose dependent manner at doses below 100 ng. However the parameters of the force exerted on the lever were differentially altered by the two drugs. Muscimol increased RTs by slowing down the force change preceding movement as well as slightly delaying its latency. While bicuculline increased drastically the force change latency. It could also speed up the force change velocity for low doses. At higher doses (up to 500 ng) both drugs produced an arrest of the performance either associated with anxiety signs (bicuculline) or dystonic movements of the head followed by body rotations (muscimol). The strong motor impairments as well as the disruption of the conditioned performances following muscimol or bicuculline microinjection in the RN suggest an important functional role for GABAergic interneurons. Under the control of cortical afferences they can modulate rubrospinal activity and participate in the triggering of a conditioned movement. PMID- 2226686 TI - Brainstem genesis of reserpine-induced ponto-geniculo-occipital waves: an electrophysiological and morphological investigation. AB - Several experimental results indicate that the peribrachial (PB) cholinergic area of the pedunculopontine nucleus is the final relay for the transfer of brainstem generated pontogeniculo-occipital (PGO) waves to the thalamus. However, the mechanisms underlying the PGO-related activity of PB neurons remain unknown. In order to study these mechanisms, single unit recordings in the PB area were performed in reserpinized cats. Because PGO waves are closely related to rapid eye movements, our microelectrode explorations were also aimed to some structures of the preoculomotor network, namely, the superior colliculus (SC) and parts of the central tegmental field (FTC). We have found several classes of PGO-on cells in the PB area, most of them descharging 80 ms or less before the peak of PGO waves. These cell-classes comprised high-frequency bursting cells, slow-frequency bursting cells, and neurons discharging single spikes or doublets. Intracellular recordings showed that PGO-on single spikes arise from conventional excitatory postsynaptic potentials. Among PGO-related cells in structures outside the PB limits, it was found that most SC cells discharge during or after the PGO, whereas FTC cells increase their discharge rate several hundreds of ms before PGO waves, thus indicating that PGO waves are elaborated long before the activation of PB neurons. Massive retrograde labeling was found in FTC following horseradish peroxidase injections into the PB area. We suggest that long-lead FTC neurons provide an excitatory input to PGO-on PB neurons. PMID- 2226687 TI - Axotomized, adult basal forebrain neurons can innervate fetal frontal cortex grafts: a double fluorescent tracer study in the rat. AB - The ability of axonal regeneration of identified adult basal forebrain (BFB) neurons was examined after homotopic grafting of fetal neocortical tissue to a lesion cavity in the frontal neocortex. Using a four step experimental procedure, adult rats first received an injection of the fluorescent dye Fluoro-Gold (FG) into the sensorimotor cortex in order to label those neurons with projections to the area by retrograde axonal transport. After one week the injection area was removed by aspiration, leaving a cavity in the neocortex. One week later a block of fetal (E14) frontal cortical tissue was placed in the cavity. The animals were then allowed to survive for 6 weeks before a second fluorescent tracer, Nuclear Yellow (NY), was injected into the transplant. The animals were sacrificed 24 h later and analyzed by fluorescence microscopy. Both single labeled, FG and NY containing neurons and double labeled neurons containing both tracers were found in the BFB. The results demonstrate that adult BFB neurons can reestablish cortical projections into fetal cortical grafts (double labeled neurons), and they suggest that other BFB neurons, not initially innervating the lesioned cortical area, have sprouted into the transplant (NY labeled neurons). PMID- 2226689 TI - Differences in coordination of elbow flexor muscles in force tasks and in movement tasks. AB - Motor-unit activity in m. biceps brachii, m. brachialis and m. brachioradialis during isometric contractions has been compared with motor-unit activity during slow voluntary (extension and flexion) movements made against external loads. During these slow movements the recruitment threshold of m. biceps motor units is considerably lower than it is during isometric contractions but the recruitment threshold of both m. brachialis and m. brachioradialis motor units is considerably higher. For all three elbow flexor muscles the motor-unit firing frequency seems to depend on the direction of movement: the firing frequency is higher during flexion movements (3 deg/s) and lower during extension movements ( 3 deg/s) than during isometric contractions. The relative contribution of the biceps to the total exerted flexion torque during slow voluntary movements is estimated to increase from 36% to about 48% and that of the brachialis/brachioradialis is estimated to decrease from 57% to about 45% compared to the relative contribution of these muscles during isometric contractions. This difference in the relative contribution of the three major elbow flexor muscles is shown to be caused by differences in the central activation in force tasks and movement tasks. PMID- 2226688 TI - Stimulation of cranial vessels excites nociceptive neurones in several thalamic nuclei of the cat. AB - Extracellular recordings were made in the thalamus of cats anaesthetized with chloralose and urethane following electrical, mechanical and chemical stimulation of the superior sagittal sinus or middle meningeal artery. Facial receptive fields were looked for using electrical and mechanical stimuli. The locations of fifty-six cells were verified histologically. Twenty six cells were located in the ventroposteromedial nucleus (VPM) and six in its ventral periphery (VPMvp). All units in VPM had facial receptive fields, usually involving the first trigeminal division. Cells with nociceptive receptive fields or responding to the craniovascular application of bradykinin were often found in the periphery or "shell" region of VPM. Other craniovascular nociceptive cells were found in VPMvp, in the posterior group and in the intralaminar complex. This study shows that craniovascular afferents in the cat project to several thalamic nuclei and implicate VPM especially in craniovascular nociception. PMID- 2226690 TI - The effect of agonist/antagonist muscle vibration on human position sense. AB - During voluntary movement, muscle spindles of both the agonist and antagonist muscles potentially can supply information about position of the limb. Muscle vibration is known to increase muscle spindle discharge and cause systematic distortions of limb position sense in humans. The following two experiments attempted to examine these contributions by separately vibrating over the triceps and biceps muscles during forearm positioning. In the first experiment, subjects performed a horizontal flexion or extension of the right arm to a mechanical stop randomly positioned at 20, 40 or 60 degrees. Vision was occluded and vibration was applied to the right arm. The perceived position of the right limb was assessed by instructing subjects to simultaneously match the right arm position with the left limb. Vibration of the shortening, agonist muscle had no effect on limb matching accuracy. However, antagonist muscle vibration resulted in a significant overestimation of the vibrated limb position by 6-13 degrees. The procedures for the second experiment were similar to the first, except that movements of the right limb were self-terminated and only flexion movements were performed. A screen was mounted over the arms and subjects were instructed to move the right arm until it was positioned beneath a marker on the screen. Vibration of the shortening agonist muscle had no effect on either the positioning accuracy of the right limb or matching accuracy of the left limb. However, antagonist muscle vibration resulted in significantly shorter movements (6-10 degrees) by the right limb and an overestimation of right limb position by the left, matching limb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226691 TI - Representation of braille characters in human nerve fibres. AB - We have used microneurographic techniques in human subjects to record mechanoreceptive afferent responses to standard Braille characters scanned across the finger pads. Responses from all four mechanoreceptor classes (FA I, FA II, SA I and SA II) have been reconstructed to form two-dimensional Spatial Event Plots (raster plots) of the Braille alphabet. Both the SA I and FA I responses resolve the dot patterns of Braille characters with sufficient fidelity that the representations of the individual characters can be recognized visually. Responses from SA II and FA II afferents do not resolve the Braille characters. We believe that the Spatial Event Plots derived from SA I and FA I responses closely approximate the images that are transmitted within a human nerve during Braille reading. PMID- 2226692 TI - Relations between identified tendon organs and motor units in the medial gastrocnemius muscle of the cat. AB - In one medial gastrocnemius muscle of each of several cats, the response was recorded of a single tendon organ to the contraction of a single motor unit which strongly excited the receptor. The motor unit was depleted of its glycogen and the depleted muscle fibres identified in PAS-stained transverse sections. The site of maximum tendon organ sensitivity was marked and the tendon organ identified in the same sections. Five pairs of tendon organs and motor units were studied completely. Each tendon organ was found to have one or two (mean 1.6) depleted muscle fibres attached to it, included in the bundle of fibres attached to the end (mean no. 14.4) and side (mean no. 5.6) of the tendon organ. A correlation was found between tendon organ discharge rate and the tension calculated from cross-sectional area measurements of the depleted muscle fibres attached to the tendon organ, with variation between individual pairs of tendon organs and motor units. One estimate of the average sensitivity of the sample was 28 imp/s/mN. A nearly linear discharge rate vs. tension relation was found for single tendon organ and motor unit pairs when tension was graded during a series of fatiguing contractions. Under these conditions the sensitivity, measured as the slope of the relation between discharge rate and motor unit tension recorded at the common tendon, varied between 0.11 and 0.30 imp/s/mN for 6 pairs. PMID- 2226693 TI - Vomeronasal activation by urine in the primate Microcebus murinus: a 2 DG study. AB - The vomeronasal system (VNS) seems to be functional in some primates and involved in the detection of urinary signals. Anterograde tracing (WGA-HRP) and evoked metabolic activity (2-DG method) were used in order to clarify the conditions under which the VNS is activated in the prosimian mouse lemur. After WGA-HRP deposition at one of the oral entries of the nasopalatine duct, reaction product was observed within the accessory bulb (AOB). 2-DG experiments show that urine in the volatile phase stimulates the main but not the accessory bulb (AOB). Liquid urine produced bilateral or unilateral activation of AOB depending on whether the stimulation was exclusively unilateral or not; under the same conditions distilled water could not produce 2-DG labelling. It is concluded that VNS is activated by urine in the liquid but not the volatile phase. The biological implications of these results are discussed. PMID- 2226694 TI - Output pathways from the rat superior colliculus mediating approach and avoidance have different sensory properties. AB - Neuroanatomical studies have demonstrated that the two major descending pathways from the superior colliculus arise from regionally segregated, distinct, cells of origin. Stimulation and lesion studies have implicated the crossed descending tecto-reticulo-spinal projection in approach movements towards novel stimuli whereas the ipsilateral pathway appears to be involved in the control of avoidance and escape-like behaviours. The present electrophysiological study attempted to characterise the sensory properties of antidromically identified cells of origin of these pathways in anaesthetised rats. We found that the contralaterally projecting predorsal bundle (PDB) efferents were primarily somatosensory while the ipsilateral cuneiform (CNF) projection was primarily visual. PDB cells, mainly found in the intermediate layers, responded principally to vibrissal stimulation with their overlying visual fields optimally stimulated by small dark moving objects in the lower rostral and lateral field. In contrast, most CNF cells were located rostromedially, with the greatest contribution from visual cells responsive to stimuli in the upper rostral field. A significant proportion of these showed no response to small moving dark discs but fired vigorously to 'looming' stimuli. Ethological considerations suggest that these are appropriate stimulus characteristics for a system controlling approach and avoidance behaviour in an animal such as the rat where predators generally appear from above and prey is found on the ground. PMID- 2226695 TI - Extensive monosynaptic inhibition of ventral respiratory group neurons by augmenting neurons in the Botzinger complex in the cat. AB - Axonal projections and synaptic connectivity of expiratory Botzinger neurons with an augmenting firing pattern (Bot-Aug neurons) to neurons in the ipsilateral ventral respiratory group (VRG) were studied in anaesthetized cats. Antidromic mapping revealed extensive axonal arborizations of Bot-Aug neurons (24 of 45) to the rostral or caudal VRG, with some having arbors in both regions. Of 234 pairs of neurons studied with intracellular recording and spike-triggered averaging, monosynaptic inhibitory postsynaptic potentials (IPSPs) were evoked in 49/221 VRG neurons by 38/98 Bot-Aug neurons. The highest incidence of monosynaptic inhibition was found in inspiratory bulbospinal neurons (10 of 23 tested). Evidence was also found for monosynaptic inhibition, by a separate group of Bot Aug neurons, of expiratory bulbospinal neurons (12/58), while excitatory postsynaptic potentials (EPSPs) were identified in another two of these neurons. In addition, monosynaptic IPSPs were recorded from 13 of 53 identified laryngeal motoneurons, and from 14 of 100 respiratory propriobulbar neurons. Presumptive disynaptic IPSPs were recorded from 11 of the 221 VRG neurons. We conclude that Bot-Aug neurons exert widespread inhibition on all major neuron categories in the ipsilateral VRG, and should be regarded as an important element in shaping the spatiotemporal output pattern of both respiratory motoneurons and premotor neurons. PMID- 2226696 TI - Topography of the facial musculature within the facial (VII) motor nucleus of the neonatal rat. AB - WGA-HRP, HRP and fluorescent tracers were used to determine the representation of the facial muscles in the facial motor nuclear complex (FMNC) of the newborn rat. Tracer injections of the superficial cervical and anterior mandibular portions of platysma, the orbicularis oculi muscle, the nasolabial musculature and the posterior auricular musculature revealed an adult-like topographic organization across FMNC subnuclei. Tracer delivery to individual vibrissa follicle loci of the whiskerpad also demonstrated an adult-like musculotopic organization within the lateral subnucleus. PMID- 2226697 TI - Direction-selective saccadic-burst neurons in the fastigial oculomotor region of the macaque. AB - Discharges of 68 neurons, recorded from the oculomotor region of the fastigial nucleus (FN) of the macaque, were characterized by a burst which started approximately 20 msec prior to the onset of a saccade in a direction contralateral to the recording site. These fastigial neurons also paused before saccades in their nonpreferred direction and then discharged with a subsequent burst. All units were spontaneously active but the tonic level of activity did not reflect eye position. They aggregated within the oculomotor region and the firing of 57 units (83.8%) was suppressed by stimulation of vermal lobule VII. Tonic discharges of six other units were closely related to eye position and located rostral to the burst units. Discharges of 16 units increased during the ipsilateral phase of sinusoidal head rotation and those of 50 units increased during contralateral head rotation. These neurons did not show saccade-related activity. They were widely scattered in the rostral and central portions of the FN. None of these units was inhibited by stimulation of vermal lobule VII. PMID- 2226698 TI - Methodology of microdialysis of neostriatum in hemiparkinsonian nonhuman primates. AB - In vivo biochemical microdialysis in primate brain would greatly expand our understanding of functional neuronal systems. This work describes our efforts to establish a microdialysis system in primate brain. Seven anesthetized rhesus monkeys underwent magnetic resonance imaging (MRI) with the head fixed in a compatible stereotaxic frame. This allowed stereotaxic localization of the caudate nucleus and putamen. Guide cannulae were implanted and fixed to the skull. Microdialysis probes made from polyethylene and fused silica were inserted into the caudate and putamen through the guide cannulae and perfused at the rate of 1.3 microliters/min. The putamens were approached horizontally, while the caudate nuclei were reached via a 30 degrees-45 degrees angle from the vertical. Postdialysis MRI and histologic evaluation proved that all probes accurately arrived at the predetermined region. Our data show that MRI guided stereotaxis allows accurate placement of dialysis probes and that implantation of guide cannulae is a reliable and convenient way to perform repeated brain microdialysis procedures. PMID- 2226700 TI - Delayed visual feedback and movement control in Parkinson's disease. AB - The dependence of movement on visual information was compared for healthy individuals and Stage II-III patients with Parkinson's disease (PD). A time delay (0-1400 ms) was introduced into a visually guided motor tracking task which required the subject to maintain constant index finger position relative to a stationary baseline on an oscilloscope. For healthy individuals, delayed visual feedback induced complex oscillations in finger displacement. Similar results were obtained for four of eight patients with PD. However, oscillations were not induced in four of eight patients with PD because of reduced gain and/or a higher tremor amplitude at zero delay which obscured the tracking error. These results suggest that some patients with PD are able to utilize visual information for controlling tracking in this motor task in the same manner as healthy individuals. PMID- 2226699 TI - Chronic levodopa impairs morphological development of grafted embryonic dopamine neurons. AB - Degeneration and plasticity of dopamine (DA) neurons may be influenced by their own neurotransmitter and/or metabolic by-products. Substances with known neurotoxic properties, such as hydrogen peroxide and 6-hydroxydopamine, are produced during oxidation of DA. Additionally, DA can directly regulate neurite outgrowth in both invertebrate and vertebrate species. We have begun to investigate the influence of increased local transmitter concentrations on the morphological plasticity of neurons by examining the effect of chronic levodopa, a drug that increases DA synthesis, on grafted embryonic nigral DA neurons in a rat model of experimental parkinsonism and in monolayer cell cultures. Results from our in vivo investigation show that although chronic levodopa does not significantly affect the number of surviving grafted cells, morphological development of these embryonic DA neurons appears impaired. Levodopa administered chronically to fetal DA neurons in culture results in a decreased number of surviving neurons as well as a reduction in neurite outgrowth with increasing concentration of levodopa ranging from 10(-8) to 10(-4) M. This information provides further evidence to support the hypothesis that excess DA or its metabolites can influence the survival and growth of DA neurons. These results may be important in the design of pharmacotherapy for Parkinson's disease and the combination of drug and neural grafting therapies in this disorder. PMID- 2226701 TI - Brugia pahangi: effects of duration of infection and parasite burden on lymphatic lesion severity, granulomatous hypersensitivity, and immune responses in jirds (Meriones unguiculatus). AB - The effects of Brugia pahangi infection duration and parasite burden on parasite associated inflammatory and immune responses were determined over a 181-day period in jirds receiving from one to eight inoculations of infective larvae. Multiple infections did not produce a protective resistance to reinfection as determined by adult worm recovery at necropsy. Intralymphatic granulomatous lesions, lymph thrombi, were first seen at 48 days post initial inoculation (DPI). The numbers of lymph thrombi reached peak levels in singly inoculated jirds at 90 DPI and significantly decreased to low levels by 160 DPI. The ratio of lymph thrombi to adult worms recovered from the spermatic cord lymphatics followed a similar pattern. Sizes of renal lymph nodes, which drain lymphatics containing parasites, followed a temporal pattern of increase and decrease similar to that of lymph thrombi numbers. Peak granuloma areas around antigen coated beads embolized in lungs were seen at 27 DPI. Granuloma areas around antigen-coated beads began to decrease after 69 DPI and reached sizes not significantly different from uninfected controls by 118 DPI. Multiple inoculations of infective larvae and increasing worm burdens did not affect the pattern of granulomatous response to antigen-coated beads. Eosinophilia of singly and multiply infected jirds peaked at 26 DPI. Eosinophilia of singly infected jirds returned to normal levels by 103 DPI but those of multiply infected jirds remained elevated until 160 DPI. Lymph node cell blastogenic responses to antigen were greater than those of splenocytes at all time intervals measured. However, significant differences in stimulation indexes between groups with different infection durations were not seen with either cell type. Antibody responses to somatic adult worm antigen as measured by ELISA reached near peak levels by 48 DPI and remained elevated for the course of the study in all infected jirds. The decrease in lymphatic lesion severity seen in chronically infected jirds temporally corresponds to the decrease in granulomatous reactivity measured around antigen-coated beads embolized in the lungs. This observation suggests that host and/or parasite factors associated with these two phenomena may be similar. Although these decreases may be the result of down-regulated immune responses, corresponding decreases in antibody levels and blastogenesis of lymphocytes stimulated by crude worm extracts were not observed in chronic infections. PMID- 2226702 TI - Dirofilaria immitis: effect on hemolymph polypeptide synthesis in Aedes aegypti during melanotic encapsulation reactions against microfilariae. AB - [35S]Methionine-labeled hemolymph polypeptides from adult, female Aedes aegypti Liverpool strain mosquitoes inoculated with the microfilariae of the filarial nematode Dirofilaria immitis were compared with those from saline-inoculated and uninoculated controls by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by fluorography. SDS-PAGE analysis of cell free hemolymph collected via perfusion at 6, 12, 24, 48, 72, and 96 hr postinoculation (PI) detected the enhanced expression of an 84-kDa polypeptide. This polypeptide, expressed constitutively in the hemolymph of all three groups of mosquitoes, increased considerably in inoculated mosquitoes as time progressed as compared with uninoculated controls. Moreover, the 84-kDa polypeptide was expressed at higher levels in D. immitis-inoculated mosquitoes than in saline inoculated controls. This stimulation of de novo biosynthesis of the 84-kDa polypeptide in inoculated mosquitoes may play a role in the immune response of mosquitoes. Since it is likely that the wound healing response in insects involves many of the same chemical processes as occur in melanotic encapsulation reactions of mosquitoes against filarial worms, the preferential expression of the 84-kDa polypeptide in saline-inoculated mosquitoes seen in this study may reflect a wound healing response. The greater increase in synthesis of this protein in D. immitis-inoculated mosquitoes may reflect production of melanotic material required for parasite destruction as well as for wound healing. PMID- 2226703 TI - Opisthorchis viverrini: finding and recognition of the fish host by the cercariae. AB - The cercaria of Opisthorchis viverrini finds and recognizes its fish host by using at least four steps of behavioral patterns. (1) Dispersal and selection of plant-free water microhabitat are achieved by intermittent swimming behavior with positive phototactic orientation. (2) Attachment to the host is stimulated by water currents and a hydrophilic component of fish skin surface which has a molecular weight of more than 30,000. This component is sensitive to digestion with hyaluronidase and seems to be a glycosaminoglycan other than hyaluronic acid and chondroitin sulfate. (3) Remaining on the host's surface is induced by an unknown chemical component of fish skin surface mucus. (4) Penetration into the host is triggered by a hydrophilic component of fish skin surface of a molecular weight of more than 30,000. This host signal has a proteinaceus character as it is sensitive to proteinase digestion but not to hyaluronidase and glycosidases. The requirement of O. viverrini cercariae for complete glycosaminoglycans and proteins as signals in host identification may have the advantage that the numerous small molecules in mud and decaying materials in the water cannot interfere with host-finding. PMID- 2226704 TI - Trypanosoma brucei: calcium-dependent endoribonuclease is associated with inhibitor protein. AB - T. brucei cytoplasmic calcium-dependent alkaline ribonuclease activity from DEAE cellulose fractionation was separated into endoribonuclease and exoribonuclease activities by hydroxyapatite chromatography. T. brucei cytoplasmic extract markedly decreased the endoribonuclease activity, but slightly potentiated the activities of the exoribonuclease and bovine ribonuclease A. While the endoribonuclease was activated by trypsin, the exoribonuclease and bovine ribonuclease A were partially inactivated by trypsin. The endoribonuclease was activated by p-chloromercuribenzoate or N-ethylmaleimide; the exoribonuclease was not affected by these sulfhydryl group reagents. Free ribonuclease was separated from the latent endoribonuclease by 1 M NaCl-Sephadex G-100 gel filtration. The results demonstrate that T. brucei cytoplasm contains a latent endoribonuclease consisting of ribonuclease and inhibitor protein. PMID- 2226705 TI - Toxoplasma gondii: immunocytochemistry of four immunodominant antigens with monoclonal antibodies. AB - Four monoclonal antibodies in which diagnostic usefulness has been observed, concerning congenital, acquired, and reactivated toxoplasmosis, were raised against Toxoplasma gondii tachyzoites in order to localize immunodominant antigens. On immunoblots, it appears that McAb IV47, McAB GII9, McAb II38, and McAb IE10 identify families of proteins with estimated molecular weights of 28-30 kDa, 30 kDa, 45-50 kDa, and 66-70 kDa, respectively. By immunogold preembedding techniques one can observe an homogeneous labeling of the outer pellicle of the tachyzoites with the McAb GII9 and IV47 and a light labeling with the McAb II38 and IE10. The three-dimensional observation of cell surface antigens is performed by applying a modified metal extraction replica method, i.e., A plasma polymerization method of glow discharge by Tanaka (1979). By immunogold preembedding techniques [with saponin permeabilization (0.1%)], and by immunogold postembedding techniques, a labeling of the rhoptries is observed with McAb GII9 and McAb IV47 but essentially all label is found with McAb II38 and IE10. With McAb GII9 a uniform labeling is observed on the cell surface. By immunoenzymatic techniques (peroxidase) a cell surface labeling is observed with the four McAb. Intracellular Toxoplasma, the outer pellicle, and the vesicles of the network (elaborated by Toxoplasma in parasitophorous vacuole) are also labeled with McAb IE10. These results indicate that McAb GII9 recognizes antigens of the antigen family (P 30) located on the cell surface and in the rhoptries. The antigen recognized by McAb IV47 is essentially located on and beneath the Toxoplasma cell surface membrane, and McAb II38 and IE10 identify preferentially rhoptry proteins. PMID- 2226706 TI - Plasmodium falciparum: ATP/ADP transport across the parasitophorous vacuolar and plasma membranes. AB - Previous studies have shown that ATP is required for the growth of the intracellular parasite, Plasmodium, outside its host cell, the erythrocyte, and that bongkrekic acid, an inhibitor of mitochondrial ATP/ADP transporter, inhibits intraerythrocytic Plasmodium maturation. We have characterized ATP/ADP transport of Plasmodium falciparum, isolated by either immune lysis or N2-cavitation. [3H]ATP uptake was due to ATP/ADP exchange since ADP efflux was dependent on exogenous ATP in an approximate 1:1 stoichiometry and both ATP influx and ADP efflux were equally inhibited by atractyloside (Ki = 100 nM). ATP uptake was not inhibited by the nucleoside transport inhibitor, nitrobenzylthioinosine. Conversely, adenosine and hypoxanthine transport were insensitive to atractyloside. ATP influx was characterized by a Km = 0.14 mM and Vmax = 1.2 nmol ATP/min/10(6) cells. Substrate specificity studies for nucleotide-induced ADP efflux indicated a preference for an adenosine ring and triphosphate, but transport did not require a hydrolyzable phosphate bond. Protein synthesis was measured with free parasites starved of glucose. Addition of 1.0 mM ATP resulted in a 40% recovery of total protein synthetic capacity in a process inhibited by 500 nM atractyloside, suggesting that uptake of erythrocyte-derived ATP by P. falciparum may be essential for maintaining maximal rates of protein synthesis during specific stages of intra-erythrocytic parasite maturation. PMID- 2226707 TI - Giardia sp.: comparison of electrophoretic karyotypes. AB - Species in the genus Giardia have been named on the basis of host specificity, cell dimensions, and median body morphology. Despite these criteria, the species taxonomy of Giardia is still in question. To investigate Giardia taxonomy on a molecular level, Giardia chromosomal DNA was analyzed by orthogonal-field alternation gel electrophoresis (OFAGE) and transverse alternating field electrophoresis (TAFE). Chromosomal DNA of G. duodenalis isolates (human, muskrat, sheep, dog, beaver), G. muris (mouse), and G. ardeae (great blue heron) were subjected to OFAGE and TAFE analyses. Comparable DNA patterns were obtained by both electrophoretic methods, but OFAGE required 8 days while TAFE required only 3 days. DNA patterns among all G. duodenalis isolates, although quite similar to each other, were distinctly different from those of G. muris and G. ardeae; G. muris and G. ardeae DNA patterns were distinctly different from each other. A G. duodenalis (Portland 1) total DNA probe hybridized to the DNA of all G. duodenalis isolates on Southern blots, but not detectably to G. muris and G. ardeae DNA. Similarly, G. muris and G. ardeae total DNA probes only hybridized detectably to their respective DNA. One probe that appears to hybridize to the DNA of all G. duodenalis and to G. ardeae DNA rather than G. muris DNA has been developed. Another probe that hybridizes only to G. muris and G. ardeae DNA has been developed. These data suggest that the differentiation of Giardia isolated from host and environmental samples may eventually be accomplished by DNA probes. Additionally, these techniques perhaps combined with other criteria may lead to the establishment of a sound taxonomic scheme for this genus. PMID- 2226708 TI - Panagrellus redivivus and Caenorhabditis elegans: evidence for the absence of sialic acids. AB - Complementary experiments were performed to indicate the presence or absence of sialic acids in axenically cultured Panagrellus redivivus and Caenorhabditis elegans. Competitive displacement experiments with radiolabeled Limax flavus agglutinin demonstrated the presence of sialic acid in nematodes grown in medium which contained liver extract as a growth factor but the absence of sialic acid when heme was substituted for liver extract. This finding suggested that sialic acid present in the liver medium was responsible for conflicting results of other studies. Transmission electron microscopy of thin sections from nematodes labeled with an LFA-ferritin conjugate revealed no label to the surface area of the cephalic chemosensilla. Fluorometric analysis with a modification of the thiobarbituric acid assay was negative for sialic acid. Analyses by gas chromatography-mass spectrometry, sensitive to the high picomole range, were also negative for sialic acid. Taken together the results provide evidence for the absence of sialic acid in P. redivivus and C. elegans using the most sensitive and diagnostic technique currently available. PMID- 2226709 TI - Onchocerca volvulus: biochemical and morphological characteristics of the surface of third- and fourth-stage larvae. AB - The annulated cuticles of third- and fourth-stage larvae of Onchocerca volvulus have the typical structure of other nematodes but the cuticle of fourth-stage larvae was thinner. The surface of the third-stage larva was wrinkled and fuzzy, while that of the fourth-stage was smooth. Intermediate stages in the formation of the new cuticle and epicuticle beneath the old basal layer and of the separation of the cuticles are shown. Monoclonal antibodies specific to the surface of third-stage larvae did not react with the surface of the fourth-stage larvae. Binding of the monoclonal antibodies to the third-stage larvae was abrogated by treatment of the worms with trypsin and proteinase K, but was unaffected by treatment with periodate or the detergents sodium deoxycholate and SDS. The lectins RCA120 and WGA, but not any of the other lectins tested, bound only to the surface of fourth-stage larvae, and not to that of third-stage larvae. The surfaces of third- and fourth-stage larvae were shown to be different and contained stage-specific surface epitopes. PMID- 2226710 TI - Arachidonic acid metabolism in filarial parasites. PMID- 2226711 TI - Intercellular dye-coupling in intestinal smooth muscle. Are gap junctions required for intercellular coupling? AB - The dye Lucifer Yellow was injected into single smooth muscle cells in the guinea pig small intestine in order to study intercellular coupling. Dye-coupling was observed in both the circular and longitudinal muscle layers and was markedly reduced when the intercellular pH was lowered. These results suggest the presence of gap junctions among intestinal muscle cells, but are inconsistent with previous ultrastructural studies that failed to demonstrate such junctions in the longitudinal muscle. PMID- 2226712 TI - Aging and endothelin-1 induced vascular contractions. AB - Contractions produced by endothelin-1 (0.3-30 nM) have been investigated in aorta, renal arteries and mesenteric arteries from 2- and 24-month-old Sprague Dawley rats. In senescent rats the EC50 values of endothelin-1 for aorta and renal artery were significantly increased (aorta: from 6.2 to 12 nM; renal artery: from 5.2 to 7.8 nM). For mesenteric artery the EC50 value (4.3 nM) was unchanged by aging, whereas the maximal contractile response to endothelin-1 was enhanced (from 8.3 to 11.7 mN). In contrast, there was no significant age-related difference in the maximal endothelin-1 response of aorta and renal artery. The present data demonstrate a reduced sensitivity for aorta and renal artery and an enhanced maximal response to endothelin-1 in the mesenteric artery in senescent rats. PMID- 2226713 TI - Lack of pyrogenic tolerance transmission between brain and periphery in the rabbit. AB - Successive injections of lipopolysaccharide (LPS) either intravenously (i.v.) or intracerebroventricularly (i.c.v.) induced pyrogenic tolerance to LPS in rabbits. Tolerance was shown by a decrease of the magnitude of the fever response to repeated doses of LPS, irrespective of the route of pyrogen administration. A significantly greater and more dramatic decrease of the fever index, however, was observed in rabbits made tolerant to pyrogen given i.v. than when the pyrogen was given i.c.v. Transmission of the pyrogenic tolerance between brain and peripheral tissues, however, has not been ascertained. PMID- 2226714 TI - Effect of feeding cereal-legume diets to rats on in vitro absorption of 45Ca. PMID- 2226716 TI - Pentobarbital-induced phase shifts of circadian rhythms of locomotor activity are not mediated through stimulated activity in mice. AB - The possibility that phase shifts of circadian rhythms of locomotor activity induced by pentobarbital injections are mediated through hyperactivity after recovery from the sedative condition was tested in DBA/2 mice. The mice were restrained for 3 h in a tube immediately after injections of pentobarbital at either CT 9 or CT 0. The results indicated that immobilization did not block the phase shifts, suggesting that pentobarbital-induced phase shifts are not due to increasing the level of activity. PMID- 2226715 TI - Irradiation of the head by 60Co opens the blood-brain barrier for drugs in rats. AB - The passage of 6 model drugs; acetylsalicylic acid, chloramphenicol, ethimizol, carbisocaine, heptacaine, and diazepam, through the blood-brain barrier, was determined in unirradiated control rats and in animals 1, 3, and 7 days after irradiation of the head only with a dose of 25 Gy from a 60Co source. The brain uptake index (BUI), which compares the uptake of the test substance with that of 3H2O 5 s after their injection into the common carotid artery, was significantly increased in comparison with unirradiated controls 7 days after irradiation, for all substances tested except for ethimizol. For acetylsalicylic acid and chloramphenicol it was also significantly increased in the other time intervals. The less lipophilic substances showed a greater relative increase of BUI than the more lipophilic ones. PMID- 2226717 TI - Effects of selective dopamine D1 and D2 antagonists on male rat sexual behavior. AB - The effects of selective dopamine (DA) D1 and D2 antagonists on male rat sexual behavior were investigated. The D1 antagonist (+)SCH-23390, 25-100 micrograms kg 1 s.c. -20 min, and the D2 antagonist raclopride, 0.1-1.6 mg kg-1 s.c., -20 min, decreased both the number of mounts and intromissions preceding ejaculation. No statistically significant effects in the time up to ejaculation or in the time up to the first intromission were noted, whereas both compounds produced a statistically significant increase in the post-ejaculatory interval. The effect can generally be characterized as psychomotor inhibition, and no evidence was obtained for a specific role of DA D1 or D2 receptors in the mediation of male rat sexual behavior. PMID- 2226718 TI - Fatty acid modulation of antiestrogen action and antiestrogen-binding protein in cultured lymphoid cells. AB - Nonsteroidal antiestrogens reversibly and specifically inhibited the proliferation of two estrogen receptor-negative lymphoid cell lines (EL4 and Raji) in a dose-dependent manner. [3H]Thymidine incorporation of concanavalin A stimulated primary splenocytes was also inhibited by 10(-6) M clomiphene (1-[4-(2 diethylaminoethoxy)phenyl]-1,2-diphenyl-2-chloroethylene). The antiproliferative effect could be prevented by the simultaneous presence in the growth medium of 10(-5) M linoleic acid or 10(-5) M arachidonic acid but not by 10(-6) M estradiol. Both lymphoid cell lines had high affinity antiestrogen-binding sites whose affinity could be altered by conditions of growth. Growth of EL4 cells in RPMI 1640 medium supplemented with charcoal-pretreated 5% fetal calf serum (charcoal-stripped medium) resulted in significantly higher affinity (Kd 0.54 nM +/- 0.11 nM; n = 6) than growth in medium supplemented with untreated serum (complete medium) (Kd = 1.68 nM +/- 0.48 nM; n = 6) (p less than 0.001). This change in affinity was partly due to removal of fatty acids from the growth medium by charcoal pretreatment, since addition of 10(-5) M linoleic acid or 10( 5) M gamma-linolenic to charcoal-stripped medium decreased the affinity of the antiestrogen-binding protein. In contrast, growth in 10(-5) M stearic acid or 10( 5) M oleic acid did not significantly alter the affinity of the antiestrogen binding protein, whereas 10(-5) M palmitic acid significantly increased its affinity. The same fatty acids were also tested for their intrinsic effects on EL4 cell proliferation. Oleic, linoleic and gamma-linolenic acids were growth stimulatory while stearic and palmitic acids were not. Thus linoleic and gamma linolenic acids whose presence in the growth medium was associated with decreased affinity of [3H]tamoxifen (1-[4-(2-dimethylaminoethoxy)phenyl]-1,2-diphenylbut 1(Z)-ene) binding to the intracellular antiestrogen-binding protein were also growth stimulatory. Unsaturated fatty acids have previously been shown to inhibit binding of [3H]tamoxifen to the antiestrogen-binding protein in a cell-free system. The present observations demonstrate that unsaturated fatty acids also modify the affinity of the antiestrogen-binding protein in intact cells. PMID- 2226719 TI - Effects of a new cholecystokinin antagonist (GE 410) on the smooth muscle of the guinea pig ileum. AB - Suc-Tyr-(SE)-Met-Gly-Trp-Met-Asp-beta-phenethylamide (GE 410) competitively antagonized the contractions of smooth muscle strips from guinea pig ileum (pA2 = 7.6, n = 0.95) induced by cholecystokinin-octapeptide (CCK8). GE 410 inhibited the electrically-induced cholinergically mediated contractile responses and the [3H]ACh release in the ileum, as well as the CCK-stimulated electrical contractile responses and the [3H]ACh release in the cholinergic nerve terminals. The results suggest the existence of CCK-receptors not only in the smooth muscles but also on the neurons. PMID- 2226720 TI - Studies on the thyroid in transgenic mice expressing the genes for human and bovine growth hormone. AB - The thyroid glands of transgenic mice (TM) expressing the genes for human (h) and bovine (b) growth hormone (GH) were studied. The percentages of larger follicles in hGH TM of either sex were significantly greater than in the corresponding normal littermates, and follicles ranging up to 350 microns in diameter were present in male hGH TM. In contrast, thyroid follicles were only slightly enlarged in male bGH TM, and were unchanged in female bGH TM. The serum concentrations of T4 were significantly decreased in male bGH TM and not altered in the other groups. Serum concentrations of T3 were slightly, but significantly increased in female hGH TM and female bGH TM, but were unaffected in male TM of either type. Since the principal difference between these foreign GHs in rodents is the additional lactogenic activity of human GH, these results may indicate that the effects of prolactin can influence the development of the thyroid. PMID- 2226721 TI - In vitro culture of chick down feather bulbi: a tool to obtain proliferating and differentiating keratinocytes in an organotypic structure. AB - Chick down feather bulbi can be cultured in different culture systems. Morphological analysis and 3H-thymidine incorporation measurements prove that the majority of cells are viable epithelial cells. PMID- 2226722 TI - Cytogenetic and biochemical comparison of Mus musculus and Mus hortulanus. AB - Two chromosome markers of Mus hortulanus are described: a dotted Y chromosome exceeding half of the length of autosome 19, and the 'domesticus' type of C banding in the X chromosome. In Mus musculus from distant regions of the USSR (more than 200 specimens of various subspecies), the Y chromosome is equal to autosome 19, and the X chromosome is of the 'molossinus' type. Specific biochemical characteristics of house mice of the USSR are shown. PMID- 2226723 TI - Transdifferentiation of larval Xenopus laevis iris under the influence of the pituitary. AB - Fragments of larval Xenopus laevis dorsal iris implanted together with the pituitary into the tail fin transdifferentiate into neural retina. On the contrary, in the control experiments the implanted tissues, dorsal iris alone, pituitary, or dorsal iris with liver fragments, do not undergo any retinal transformation. PMID- 2226724 TI - A novel reaction time task for investigating force and time parameters of locomotor initiation in rats. AB - A novel simple reaction-time task for rats is described in the present study. Food-deprived rats were trained in a modified runway for rapid locomotor initiation, in response to a combined optical/acoustic stimulus, to receive a food reward. Rats rapidly learned this task with small variability, and movement patterns of locomotor initiation are congruent under these conditions. Reaction time, movement time and accelerative forces were recorded from each initiation of locomotion by means of video equipment and a force platform. The quantification modes yielded consistent results and a quantitative description of measured force and time parameters is given. The task may be especially appropriate for investigating basal ganglia functions. The present results will be the basis for investigating initiation of locomotion in animal models of neurological diseases. PMID- 2226725 TI - Diagnostic value of glycosylated hemoglobin in intravascular hemolysis after cardiac surgery. AB - Glycosylated hemoglobin (GH), hemoglobin (Hb), hematocrit, LDH and serum bilirubin were measured pre-operatively, and 1-10 days and 11-42 d post operatively in 42 patients undergoing cardiac surgery. Their mean age was 39.90 years, ranging from 4 to 68 yr. In the early post-operation days, Hb and hematocrit, but not GH percentage, were significantly decreased. This demonstrates that, at this stage, acute blood loss rather than hemolysis is more prominent. In the later post-operative days, GH, but not Hb or hematocrit, decreased significantly. This indicates the presence of chronic hemolysis with bone marrow compensation. In our study, the incidence of chronic mild hemolysis after cardiac surgery was very high (68.8%). We conclude that GH determination is a simple, easy and sensitive method to detect chronic hemolysis and we suggest measuring it in every case with suspicion of hemolysis. PMID- 2226726 TI - Serum homocysteine in routine evaluation of potential vitamin B12 and folate deficiency. AB - Total serum homocysteine (Hcy) was measured in patients with either low serum folate, low serum vitamin B12 (B12), or potential metabolic defects, in order to evaluate Hcy as an indicator of the tissue status of the two vitamins. An increased Hcy supported the diagnosis of frank tissue deficiency in those patients in whom tissue deficiency was evident by other means. A Hcy within the reference interval enabled the clinician to identify those patients whose low serum vitamin level and symptoms did not reflect a tissue deficiency of B12 or folate of clinical consequence. Children with inherited disturbances of B12 metabolism, and whose serum B12 was within the reference interval, were correctly identified by an increased Hcy. A declining Hcy was evidence of correction of a deficiency even when other laboratory or clinical measurements of a response were obscured. PMID- 2226727 TI - Structural chromosomal abnormalities of 3q in myelodysplastic syndrome/acute myeloid leukaemia with Sweet's syndrome. AB - Structural rearrangements in the long arm of chromosome 3, del(3)(q12q25) and t(3;5)(q21-25;q31-33), were observed in bone marrow cells from 2 patients with myeloid neoplastic disorders (myelodysplastic syndrome and acute myeloid leukaemia) and acute febrile neutrophil dermatosis (Sweet's syndrome). 3 of the 4 patients with leukaemia-associated Sweet's syndrome and acquired chromosome abnormalities known from the literature also had 3q changes, in 2 involving band 3q21. PMID- 2226728 TI - Tumor-necrosis factor induces cell cycle arrest in multipotential hematopoietic stem cells: a possible radioprotective mechanism. AB - Tumor-necrosis factor (TNF) and interleukin-1 (IL-1) have been shown to confer protection of hematopoiesis in mice challenged with radiation. Herein, a series of experiments designed to elucidate the underlying mechanism is presented. After TNF administration, colony-stimulating activity, but no IL-1 activity, was detectable in mouse plasma. In endogenous CFU-S assays, TNF enhanced the survival of multipotential progenitors when administered before, but not after, irradiation. In experiments with fractionated irradiation, the radioprotective effect of TNF was distinctly different from that of IL-1. In vivo and in vitro thymidine suicide assays demonstrated that TNF wholly or partially abolished cell cycling of the CFU-S hematopoietic compartment. These data imply that TNF may inhibit the cell cycle in hematopoietic progenitor cell populations. PMID- 2226729 TI - High-dose cytosine arabinoside and amsacrine or mitoxantrone in relapsed and refractory acute myeloid leukaemia: a prospective randomized study. AB - 52 patients with refractory or relapsed acute myeloid leukaemia (AML) were randomly assigned to receive a combination of high-dose cytosine arabinoside (HD Ara-C), 3 g/m2/d and either mitoxantrone (MTX), 7 mg/m2/d (5 mg if older than 60 yr) or m-amsacrine (AMSA), 120 mg/m2/d (90 mg if older than 60 yr) for 5 d. The overall response rate was 50% and did not differ significantly in the two groups (46% for AMSA and 56% for MTX, p = 0.415). The median survival was 11 months (8 months for AMSA and 12 months for MTX, p = 0.326) and the median duration of complete remission (CR) was 11 months for AMSA and 12 months for MTX (p = 0.643). In relapsed patients, the only significant predictive factor for obtaining a complete response was the length of first complete remission. Patients with a first CR shorter than 6 months had a CR rate of 36% while it was 65% if the first CR lasted more than 6 months (p = 0.03). Severe (WHO grade III-IV) gastro intestinal toxicity was more frequent in the AMSA group (27% vs 4%, p = 0.021). Treatment-related death occurred in 4 patients in the AMSA group and in 2 patients in the MTX group (p = 0.097). We conclude that neither of these two treatment modalities was shown to be superior in terms of CR rate and survival, with a better tolerance for MTX. PMID- 2226730 TI - Immunophenotype of hairy-cell leukemia. AB - 15 cases of HCL were studied with a panel of monoclonal antibodies against different leukocyte antigens. A B-cell phenotype different from that of B-CLL was observed (CD10-, CD19+, CD20+, CD21-, CD22+, CD37+, CD38-, FMC7+, LN1+, PCA-1+, BLy7+ and CD5-). As expected, CD11c and CD25 were positive and, in addition, a My7 and My9 positivity in varying degree was noted. 3 weeks of in vitro incubation did not significantly alter the phenotype. We conclude that HCL exhibits a unique phenotype among chronic B-cell leukemias, which is closer to the plasma cell stage of differentiation than that of B-CLL. The BLy7 monoclonal antibody seems to be a promising marker for HCL. PMID- 2226731 TI - Chronic granulocytic leukaemia in asplenic patients. PMID- 2226732 TI - Effects of a mixed physical activity (biathlon) on haematologic parameters, red cell 2,3-DPG and creatine, serum erythropoietin, urinary enzymes and microalbumin. PMID- 2226733 TI - Idarubicin plus attenuated high-dose cytosine arabinoside in the treatment of relapsed and refractory acute leukemia. PMID- 2226734 TI - GM-CSF in busulfan overdosage. PMID- 2226735 TI - Sweet's syndrome in association with myelodysplastic syndrome. PMID- 2226736 TI - Effect of 52 monoclonal antibodies against platelet membrane on platelet aggregation and release reaction. PMID- 2226737 TI - Prognostic factors in multiple myeloma in a population-based trial. AB - Prognostic factors have been tested in patients with multiple myeloma treated according to a randomized trial of standard therapy versus 5-drug combination therapy. The following population-based study included 92 patients with a median age of 70 yr. The median survival was 31 months. The Cox regression model was used to search for predictors of survival. The cut-off levels for blood analyses derived in earlier studies tended to select few patients in the high-risk groups, for example only 8% of the patients had hemoglobin (Hb) less than or equal to 7.5 g/dl. Lytic bone lesions in the pelvis or in the long bones, or spontaneous fractures and age greater than 70 yr gave prognostic information in addition to anemia and impaired renal function. The MRC staging system was a better prognostic tool than the Durie & Salmon stages. Palliative treatment regimens which take quality of life into account should be considered carefully in multiple myeloma patients greater than 70 yr. PMID- 2226738 TI - Bone marrow stromal elements in murine leukemia: decreased CSF-producing fibroblasts and normal IL-1 expression by macrophages. AB - A study of bone marrow stromal elements in murine acute myeloid leukemia (AML) was carried out. Our previous studies had indicated marrow stromal deficiency in murine AML. In the current investigation, separate stromal cells were cultured and the results obtained have shown that, while marrow stromal macrophages are normal in leukemia and express adequate amounts of IL-1, the fibroblasts are markedly reduced. However, if sufficient fibroblasts are pooled in vitro, they produce adequate amounts of CSF. Test of TNF alpha in leukemic cells CM, as possible cause of marrow stromal inhibition in leukemia, had not disclosed this cytokine. Further, it was observed that total body lethal irradiation of leukemic mice aggravates the stromal deficiency, confirming results of our previous investigations. It is concluded that bone marrow stromal deficiency in murine AML is due to decreased fibroblasts and, implicitly, reduced CSF production. PMID- 2226739 TI - Abnormal chromatin clumping in leucocytes: a clue to a new subtype of myelodysplastic syndrome. AB - We report 6 patients with myelodysplastic syndrome, all of whom showed a bizarre nuclear anomaly within the neutrophils that was characterized by extensive clumping of chromatin into large blocks separated by clear zones, generally associated with a lack of segmentation. Anaemia, thrombocytopenia, variable leucocyte counts with leucoerythroblastic picture, marrow hypercellularity with granulocytic hyperplasia and moderate dysplastic changes in erythroblastic and megakaryocytic lines were present at diagnosis. 2 patients had normal karyotypes and a 3 showed a deletion of chromosome 14. 5 out of 6 patients had pneumonia at diagnosis. The median survival was short (5 months) and haemorrhagic complications were the cause of death in 4 patients. The clinical features and the evolution of these and other reported cases suggest that the presence of abnormal chromatin clumping in leucocytes might be a clue to a new subtype of myelodysplastic syndrome. PMID- 2226741 TI - Acute myelofibrosis. Case report and review of the literature. PMID- 2226740 TI - Labelling autologous platelets with 111In tropolonate for platelet kinetic studies: limitations imposed by thrombocytopenia. AB - An in vitro method of radiolabelling platelets with 111In tropolonate in plasma has been devised enabling imaging and cell kinetic studies to be performed in patients with thrombocytopenia (TP) using autologous, rather than donor, platelets. Platelets from 10 TP patients, with platelet counts ranging from 4-91 x 10(9)/l, were labelled in 50% plasma with 111In tropolonate, containing the optimum tropolone concentration of 2 x 10(-4) mol/l, at platelet concentrations ranging from 0.08-4.5 x 10(9)/ml resulting in labelling efficiencies (LE) between 51 and 86%. In 4 patients, red cells contaminated the platelets but this was corrected for by measuring the proportion of 111In on the platelets prior to injection and in the post-injection blood samples. Platelet recovery (PR), mean platelet life-span (MPLS) and platelet production rate (PPR) were calculated and splenic and hepatic images were taken. The results clearly show that useful clinical data can be obtained by this method even in patients with severe TP. PMID- 2226742 TI - Autoantibody occurrence in hairy-cell leukemia during prolonged interferon treatment. PMID- 2226744 TI - Cytogenetics in multiple myeloma: are we studying the 'right' cells? PMID- 2226743 TI - Differential expression of LFA-1 alpha molecule in clinical stages of chronic B lymphocytic leukemia patients. PMID- 2226745 TI - Low-income women's perceptions of family planning service alternatives. AB - A sample of 665 low-income women from a predominantly rural area of north central Florida rated the value of 25 features of family planning providers and reported their perceptions of how characteristic each feature was of different types of providers. A well-trained, trustworthy and friendly staff, the presence of a doctor if you need one and a staff that is gentle with the examination were the most desirable features of family planning services. The respondents' perceptions of public health clinics suggest that the strongest qualities of such facilities are that they treat people from different backgrounds, accept Medicaid, are easy to find and teach you how to avoid pregnancy and how to take care of yourself and stay healthy. Features thought most characteristic of private physician services were a well-trained staff, privacy and the presence of a doctor if you need one. Voluntary organizations were seen as providing services for people of different backgrounds, having a friendly staff, serving as a referral agency and teaching about staying healthy and avoiding pregnancy. However, voluntary organizations were rated lower than public health clinics or private physicians on nearly all features. The total scores for public health clinics and private physicians were not significantly different from each other, but both were noticeably higher than the score for voluntary organizations. Ethnicity affected ratings dramatically, with black respondents clearly more favorable toward public health clinics and private physicians than white respondents; conversely, whites were more positive toward voluntary organizations than were blacks. For many of these low-income respondents, the high ratings of private physicians may have represented their expectations rather than their actual experience. PMID- 2226746 TI - Factors associated with the use of court bypass by minors to obtain abortions. AB - Interviews with minors at four Minnesota abortion clinics revealed that 43 percent used the court bypass option that is part of that state's parental notification statute. The proportion who did so increased with age and was most common among lower socioeconomic groups. A discriminant function analysis showed that perceived maternal supportiveness was a key difference between those who went to court and those who notified their parents. Young women who attended religious services frequently were less likely than those who did not tell their parents of their abortion plans. Minors who notified only one parent--and still had to go to court under Minnesota law, which requires notification of both parents--were more likely than those who told neither to come from a single parent household and to have good communication with their mother. PMID- 2226747 TI - Trends in use of oral contraceptives--data from the 1987 National Health Interview Survey. AB - Despite fluctuations in current use rates for oral contraceptives, ever-use of the pill has remained remarkably stable for all cohorts of U.S. women born since 1945. Approximately 80 percent of these women report having used the pill at some time. Average duration of use is about five years among cohorts who had access to the pill from their earliest reproductive years. Among women born before 1940, whites are more likely than blacks to have ever used the pill, but no racial difference is evident among women in later cohorts. Age at first use of the pill has declined with each succeeding five-year birth cohort. Black women are more likely than white women to have used oral contraceptives before age 18, but by age 25, about three-fourths of blacks and whites have used the pill. Among ever users born before 1945, the majority began taking the pill after their first full term pregnancy; this pattern is reversed among more recent cohorts. PMID- 2226749 TI - The Supreme Court upholds parental notice requirements. PMID- 2226748 TI - At pill's 30th birthday, breast cancer question is unresolved. PMID- 2226750 TI - The Supreme Court retreats another step on abortion. PMID- 2226751 TI - [Attenuation of the effect of imizin on the dynamics of forced swimming and the circadian rhythm of mobility in rats chronically administered melatonin]. AB - Imizine (10 mg/kg, 14 days) was shown to change the temporal dynamics of forced swimming in rats and to decrease the biorhythmical index of depression. The antidepressant also produced reorganization of the circadian rest-activity rhythm with the acrophase shift for the late night hours. A pineal hormone melatonin (1 and 10 mg/kg, 7 days) administered in combination with imizine attenuated the main rhythmic indices of its action and precipitated the occurrence of tolerance. PMID- 2226752 TI - [The effect of antidepressants on the experimental anticonvulsant activity and acute toxicity of anticonvulsants]. AB - In the experiments on white mice there was studied the anticonvulsant activity by the test of the maximal electric shock and acute toxicity of anticonvulsants and antidepressants at separate and combined administration. The combined use of anticonvulsants and antidepressants showed the increase of the anticonvulsant activity of phenobarbital with amitriptyline, levomepromazine and lithium oxybutyrate; diphenine and carbamazepine with amitriptyline as well as hexamidine with all antidepressants. The combination of phenobarbital with amitriptyline, levomepromazine and lithium oxybutyrate, diphenine with amitriptyline, hexamidine with amitriptyline and imizine proved to be the safest. PMID- 2226753 TI - [The analgesic activity of coordination compounds of methionine enkephalin with divalent metals]. AB - Coordination compounds of methenkephalin with transition metals: copper, cobalt, nickel and zinc were shown to be superior to morphine by the analgesic activity and to morphine and methenkephalin by the duration of the analgesic effect. A more stable relationship between opiate receptors and copper-containing methenkephalin was shown in the experiments on the isolated neuronal membrane. PMID- 2226754 TI - [The effect of anti-arrhythmia agents on ventricular arrhythmias arising as a consequence of disorders in the myocardial blood supply]. AB - The protective and therapeutic effects of some antiarrhythmic drugs of classes I IV were studied in the experiments on 103 cats and 75 dogs. The antiarrhythmic drugs of classes 1a (N-propylaimaline bromide, aimaline, ethacizine), 1b (trimecaine) and IV (finoptine) were shown to prevent with various effectiveness the occurrence of early occlusion and reperfusion ventricular arrhythmias. The antiarrhythmic drugs of classes II (anapriline) and III (cordaron) proved to be ineffective in these cases. Ventricular arrhythmia in dogs occurring at the late stage of experimental infarction is reliably relieved in all cases with the antiarrhythmic drugs of class 1a, in most cases--those of classes 1b and III. The antiarrhythmic drugs of classes II and III are ineffective on this model. The experimental results analysed with regard to modern concepts of the genesis of modelled arrhythmias may be used as the experimental basis for a rational choice of antiarrhythmic drugs. PMID- 2226755 TI - [The effect on gastric secretion and the anti-ulcer action of imidazo[1,2 A]benzimidazole derivatives]. AB - The experiments on rats showed that of 16 studied imidazo [1,2-a]benzimidazole derivatives only the compounds with phenyl at the second carbon atom and nitrogen containing radical of the ninth nitrogen atom inhibit the gastric acid secretion. The binding of oxymethyl group to phenyl, its substitution through adamantyl, displacement of nitrogen-containing substitute to the first nitrogen atom or its substitution were found to decrease or stop the inhibiting action of these substances on the gastric parietal cells. Dihydrochloride 2-phenyl-9 (beta diethyl-aminoethyl)imidazo [1,2-a]denzimidazole was more potent than cimetidine and omeprazole in inhibiting the gastric acid secretion, pepsin output and antiulcer action. PMID- 2226756 TI - [The liver-protective properties of D-glucosamine]. AB - The antioxidant and membrane-stabilizing activities of D-glucosamine were studied on two models of toxic liver damage. When administered in a dose of 50 mg/kg, D glucosamine was found to prevent the development of the hepatocyte cytolysis syndrome, to normalize the cholate- and glycogen-synthetic functions of the liver. D-glucosamine exhibited a significant anabolic effect that also supplemented its hepatoprotective activity. PMID- 2226757 TI - [The effect of cholagogic preparations and Essentiale on the natriuretic hormone content of the blood plasma and on kidney function in patients with liver pathology]. AB - The effect of cholagogic drugs on blood plasma content of natriuretic hormone (NH) in 41 patients with chronic opisthorchiasis was studied. The drugs were found to exert no effect on NH content and the kidney function in this pathology. The use of essentiale in patients with persistent hepatitis and cirrhosis of the liver was shown to increase sodium excretion due to an increase of NH content. PMID- 2226758 TI - [The effect of tefestrol on the secretion of luteinizing hormone from the hypophysis]. AB - The effect of tefestrol on the content of luteinising hormone in blood and hypophysis in female and male rats was studied on the basis of the radioimmunological assays. It was shown that administration of tefestrol to the female rats depending on the preparation dose and the time of administration during the estrous cycle can produce an increase and a decrease of luteinising hormone content in the material under study. In the male rats tefestrol induced a stable elevation of blood gonadotropine level. The results obtained suggest that tefestrol may be used as a stimulant of the reproductive function and also as a contraceptive depending on the dose and the functional state of the reproductive system during the treatment. PMID- 2226759 TI - [The content of a heparin-like anticoagulant in the flowers of the meadowsweet (Filipendula ulmaria)]. AB - The flowers of Filipendula ulmaria were found to contain heparin bound to the plant proteins in the form of a complex. This complex enhances the anticoagulant and fibrinolytic properties of the nonenzymatic nature at its administration to animals both intramuscularly and intravenously. The neutralizing effect of protaminesulphate on the anticoagulant activity of the plant heparin was shown. The identity of the action on the hemostasis system of heparin of animal and plant origin was found. PMID- 2226760 TI - [The similarity of the pathogenetic mechanisms of alcoholism and drug dependence and the means of searching for agents for treating these diseases]. AB - The concept of the principal unity of the pivotal mechanisms underlying the formation of the syndrome of dependence on alcohol and various narcotic agents is presented. The central link of the mechanisms is the totality of the specific disturbances of neurochemical processes among which of particular importance are the specific changes in the functional state of catecholamine system. The theoretical approaches to the development of medicinal agents for treating alcoholism and drug addictions are considered. As an example there are discussed the results of using small doses of dopamine receptor stimulants (apomorphine and bromocriptine) and a neuropeptide cholecystokinin. PMID- 2226761 TI - [A pharmacological analysis of the cholinergic system in animals with alloxan diabetes]. AB - In the animal experiment the sensitivity to acetylcholine was shown to increase in alloxan-induced hypoinsulinemia. The blockade of M-cholinoreactive structure produced by administration of amizil caused a deterioration of the condition of the animals with alloxan-induced diabetes. The increased sensitivity to acetylcholine was accompanied by changes in the activity of acetylcholine esterase in the hypothalamus nuclei. PMID- 2226762 TI - [An analysis of the structure of the metabolic products of methandrostenolone in the body of white rats]. AB - The products of biotransformation of an anabolic steroidal drug methandrostenolone in the Wistar albino rat organism were studied. By using the developed methods of HPLC the products of a complete reduction of methandrostenolone were isolated and their chemical structures were determined. It was found that at the reduction of the system of methandrostenolone double bonds were formed all four possible isomers. PMID- 2226763 TI - [The effect of x-ray contrast agents on the concentration and size of immune complexes in the blood]. AB - Bilignost, iodamide and triombrast were shown to increase the concentration and to decrease the size of the rat blood serum immune complexes in vivo and in vitro. A decrease of the size of immune complexes was also observed during angiography with the use of triombrast in humans. According to the relation to the action of roentgen contrast media on the concentration and size of immune complexes humans and rats can be divided in "sensitive" and "tolerant" ones. PMID- 2226765 TI - [The effect of dopamine on diuresis in newborn infants with the hypodynamic syndrome of pulmonary heart failure]. AB - The effects of three dosages of dopamine (0.2-3.0, 3.1-8.0, 8.1-22.0 mg/kg/min) on diuresis were studied in 28 neonates with cardiopulmonary insufficiency. The relationship between the ability of dopamine to increase diuresis and an elevation of the lowered arterial blood pressure as well as the degree of acid base condition compensation was revealed. PMID- 2226764 TI - [The effect of parmidine on the lipid peroxidation processes in coronary atherosclerosis]. AB - During the formation and development of atherosclerosis the intensity of lipid peroxidation and the activity of antioxidant defence system significantly change. The use of parmidine decreases the contents of primary and secondary products of lipid peroxidation, reduces peroxide hemolysis of erythrocytes and increases the content of reduced glutathione in erythrocytes of patients with atherosclerosis. This shows that parmidine possessing the antioxidant properties stabilizes lipid peroxidation processes and normalizes the physiological antioxidant system. PMID- 2226767 TI - [Free amino acids of the liver and the characteristics of the amino acid metabolism in the liver and brain after cyanamide administration to rats]. AB - A single administration to rats of cyanamide (60 mg/kg, for 1 hour) was found to decrease the contents of cysteate, serine, glutamate, glycine, alanine, valine, methionine, isoleucine, tyrosine, ethanolamine, ornithine and histidine that may be considered as a manifestation on the drug hepatotoxicity. The activities of transaminases, glutamate dehydrogenase, pyruvate dehydrogenase remained unchanged. Cyanamide effects were considerably abolished by the supplementary ethanol administration (0.5 g/kg). Cyanamide failed to affect vitamin-dependent enzymes reflecting thiamine pyrophosphate, pyridoxal phosphate and flavine adenine dinucleotide status of the rat organism. PMID- 2226766 TI - [The effect of a fluorocarbon emulsion--an enzyme inducer of the cytochrome P-450 dependent monooxygenase system of the liver--on the acute toxicity of CCl4 and on the efficacy of the prophylactic use of antidotes in organophosphate pesticide poisoning]. AB - The effect of intraperitoneal administration of perfluorocarbon emulsion, an inducer of cytochrome P-450-dependent monoxygenase system of the liver, on the resistance of rodents to the action of CCl4 and organophosphorus pesticides was studied. Perfluorocarbon emulsion potentiated CCl4 toxicity decreasing LD50 from 4.5 to 3.7 mg/kg mouse body weight without changing susceptibility of rats to organophosphorus pesticides. A preliminary administration of perfluorocarbon emulsion effectively increased the protective action of antidotes (atropine + dipyroxime) providing the resistance of the animals to 12-fold, 20-fold and 20 fold LD50 of dichlophos, methaphos and butiphos, respectively. PMID- 2226768 TI - [The antiedematous activity of a table salt substitute, veroshpiron and furosemide in experimental circulatory failure]. AB - On the model of circulatory insufficiency and secondary aldosteronism in rats it was shown that a new table salt substitute normalizes like spironolactone the extracellular fluid volume whereas furosemide exerts a less marked dehydrating action. The antiedema effect of the substitute of table salt is due to a decrease in drinking activity, an increase in natriuresis, normalization of aldosteronism. PMID- 2226769 TI - [Psychomotor stimulants as agents for enhancing work capacity]. AB - Amphetamine, methamphetamine, pemoline, sydnocarb and other psychomotor stimulants derived from phenylethylamine are referred as the most effective agents for an urgent increase of performance. Their positive effect is however reduced or even transformed in a nonbeneficial one if the work is of the complex nature or is performed under emotional stress, overfatigue, hypoxia, overheating. The psychomotor stimulants, in particular amphetamine and methamphetamine, can cause attacks of angina pectoris, arrhythmias, an elevation of arterial blood pressure, drug addiction, anxiety or aggressive behavior, psychotic reactions. PMID- 2226770 TI - [Modern concepts of neurotoxicity]. AB - A systematic analysis of the main literature published in the recent five years which reflects a variety of aspects of research on specifics of the nervous system reactions in humans and animals to effects of neurotropic chemical products was performed. The further insight into the essence of neurotoxicity would contribute to the development of necessary measures for prevention and therapy of exogenous neurointoxications. PMID- 2226771 TI - [The undesirable action of drugs on the embryo, fetus and newborn infant]. AB - The up-to-date data on the negative influence of various drugs on the intrauterine development and postnatal condition of the human fetus and neonate are presented. The embryotoxic, teratogenic and fetotoxic effects of drugs are considered. The data on the teratogenic action of drugs taken not only by the mother but by the father as well, the behavioral teratology, disturbances in the condition of the neonate whose mother received some drugs during labour are given. PMID- 2226772 TI - [The problems of the experimental and clinical pharmacology of vein-tonicizing agents]. AB - General regularities of changes in the regional venous and systemic hemodynamics under the influence of venotropic drugs are considered. Particular emphasis is given to problems of pharmacodynamics of venotropic agents. The mechanisms of their action, similarity and differences in phlebohemodynamic effects, problems of clinical use and also prospects of the further research on pharmacology of venotropic agents are discussed. PMID- 2226773 TI - Overexpression of glucose transporter modulates insulin biosynthesis in insulin producing cell line. AB - Glucose transporter (GT) has been suggested to be involved in the insulin biosynthesis. However, the functional relationship between GT and insulin biosynthesis is not well understood. In this report, we have generated rat pancreatic B cell lines (RINr) that stably overexpress a cDNA encoding the brain type GT. These cell lines showed 3- to 4-fold increase in insulin mRNA and protein. These results suggest that GT might have some relationship to the insulin biosynthesis in the pancreatic B cells. PMID- 2226774 TI - A single cell observation of staurosporine effect on the Ca2+ signals in rat basophilic leukemia cells. AB - A digital imaging fluorescence microscope was used to study the effect of a protein kinase inhibitor staurosporine on the antigen-dependent calcium signals in an individual rat basophilic leukemia cell (RBL-2H3). Although dose dependency of staurosporine was different from one cell to another, staurosporine inhibited, at low concentration, the calcium influx from the external medium into RBL-2H3 cells. At high concentration, however, it inhibited both the removal of calcium ion from internal stores and the calcium influx from the external medium. These results indicated that staurosporine is necessary for the inhibition of the calcium influx from the external medium and that a protein kinase (possibly protein kinase C) is involved in the calcium influx from the external medium into the cytoplasm. PMID- 2226775 TI - In vivo and in vitro mutants of FNR the anaerobic transcriptional regulator of E. coli. AB - FNR regulates the expression of target genes in response to anaerobiosis. It resembles the catabolite gene activator or cAMP-receptor protein (CRP) except for the presence of an N-terminal cysteine cluster, which may form a redox-sensing iron-binding site. Site-directed mutagenesis has shown that 3 of the 4 cysteine residues in the N-terminal cluster (Cys-20, -23 and -29, but not Cys-16) and the only other cysteine residue (Cys-122), are essential for the normal activation and repression of FNR-dependent promoters. Deletion of residues Pro-3-Arg-9 (inclusive) had no effect, but FNR was inactivated by a frameshift extending through the C-terminal DNA-binding domain. Four independent in vivo mutants contained identical Gly-96----Asp substitutions, which may inactivate FNR by distorting a sharp turn between beta-strands in the predicted structure. PMID- 2226776 TI - Revised structure of the peptide lactone antibiotic, TL-119 and/or A-3302-B. AB - The peptide lactone antibiotic TL-119 and/or A-3302-B was chemically synthesized in order to confirm the proposed structure. The synthetic compound was different from both natural TL-119 and A-3302-B in their physicochemical properties and in biological activity. Re-examination of the configuration of the constituent amino acid residues in natural TL-119 and/or A-3302-B indicated that natural TL-119 and A-3302-B contains D-aThr instead of the original L-Thr. We tentatively propose a revised structure for TL-119 and/or A-3302-B. PMID- 2226777 TI - N-myc suppression and cell cycle arrest at G1 phase by prostaglandins. AB - Effects of cyclopentenone prostaglandins, delta 12-prostaglandin (PG) J2 and PGA2 on the expression of N-myc in relation to the effects on cell cycle progression were investigated using human neuroblastoma cell line GOTO. Both PGs suppressed N myc expression within several hours prior to inducing G1 arrest. The N-myc suppression with delta 12-PGJ2 was continued but with PGA2 it was gradually released, followed by the release of G1 arrest. These results suggest that delta 12-PGJ2 and PGA2 inhibit cell cycle progression in strong association with N-myc suppression and delta 12-PGJ2 is more potent and has a longer effect than PGA2. PMID- 2226778 TI - Differential regulation of interleukin-6 expression in human fibroblasts by tumor necrosis factor-alpha and lymphotoxin. AB - The treatment of human diploid fibroblasts with tumor necrosis factor (TNF)-alpha and with lymphotoxin (LT) is associated with induction of interleukin-6 (IL-6) transcripts with TNF-alpha being 10-fold more potent than LT. Here we report on the TNF-alpha/LT-induced signaling mechanisms responsible for the regulation of IL-6 gene expression in these cells. Run-on assays demonstrated that both TNF alpha and LT increase IL-6 mRNA levels by transcriptional activation of this gene. Stability studies of IL-6 transcripts in fibroblasts showed that TNF-alpha delayed IL-6 mRNA decay but not LT. The induction of IL-6 transcripts by TNF alpha and LT was not inhibited by the isoquinoline sulfonamide derivative H7. Similarly, depletion of protein kinase C (PKC) by 12-O-tetradecanoyl-phorbol 13 acetate (TPA) did not change the ability of TNF-alpha and LT to induce IL-6 transcripts, demonstrating that stimulation by these agents may not be mediated by activation of PKC. Stimulation of IL-6 transcripts in fibroblasts did also not require new protein synthesis as exposure to the protein synthesis inhibitor cycloheximide (CHX) enhanced accumulation of IL-6 mRNA in the presence or absence of TNF-alpha or LT. PMID- 2226779 TI - Flight and heat dissipation in birds. A possible molecular mechanism. AB - Birds during normal sustained flight must be able to dissipate more than 8 times as much heat as during rest in order not to be overheated. The experiments reported in this note on the hemoglobin systems from two different birds indicate the existence of a molecular mechanism by which hemoglobin is used simultaneously for oxygen transport and heat dissipation. PMID- 2226780 TI - Clear cell carcinoma of the human ovary synthesizes and secretes a transferrin with microheterogeneity of lectin affinity. AB - Human ovarian clear cell carcinoma cell line (transferrin (Tf)-non-producer), HAC 2, cells were adapted to grow in chemically defined synthetic medium when the cells were cultured with medium containing 10 micrograms/ml of insulin at least for 6 months. They synthesized and secreted constantly the 80 kDa protein immunologically similar to human serum Tf (15 +/- 12 ng/ml/10(7) cells/3 days). By sensitive lectin-affinity electrophoresis followed by antibody-affinity blotting technique, a concanavalin A weakly bound or unbound, lentil lectin, a strongly reactive abnormal band, which was rarely found in human serum Tf, was detectable in the Tf synthesized by HAC 2 cells (HACTf). These findings suggest that the HACTf may act as one of the autocrine growth factors and that this heterogeneity of HACTf for lectin affinity is ascribed to differences in the carbohydrate moiety of the Tf. PMID- 2226781 TI - gamma-Purothionins: amino acid sequence of two polypeptides of a new family of thionins from wheat endosperm. AB - Two homologous sulfur-rich basic polypeptides form wheat endosperm, so-called gamma 1-purothionin and gamma 2-purothionin, are described. Purification involves extraction with volatile solvents and ammonium bicarbonate fractionation followed by reversed-phase high-performance liquid chromatography. The complete primary structure of these two polypeptides has been determined by automatic degradation of the intact, S-carboxymethylated gamma-purothionins and peptides obtained by enzymatic cleavage. gamma 1-Purothionin and gamma 2-purothionnin consist of 47 amino acids with an molecular weight of 5239 and 5151 Da, respectively and 8 cysteines organized in 4 disulfide bridges. They present a high degree of homology among themselves (89% of identity) and are the first two thionin-like polypeptides, so-called gamma-thionins, described from wheat endosperm. PMID- 2226782 TI - Sodium-activated potassium current in mouse diaphragm. AB - The mouse diaphragm muscle fiber was studied using the loose patch clamp technique. The voltage gated sodium currents were evoked by step pulses from a holding potential of about - 70 mV. Following the activation of the sodium current, a very large and fast outward current was evoked. The sensitivity of this current to 4-aminopyridine and tetraethylammonium indicates the potassium ion as the possible carrier for the channel. Furthermore, the sensitivity to tetrodotoxin and extracellular sodium demonstrated the sodium dependence of this current. PMID- 2226783 TI - Amino acid sequence elucidation of human acrosin-trypsin inhibitor (HUSI-II) reveals that Kazal-type proteinase inhibitors are structurally related to beta subunits of glycoprotein hormones. AB - The amino acid sequence of the acrosin-trypsin inhibitor HUSI-II from human seminal plasma is presented which unequivocally identifies HUSI-II as being of Kazal-type. In addition, the HUSI-II sequence shows a striking similarity to the middle part of glycoprotein hormone beta-subunits thus revealing a hitherto unknown structural and evolutionary relationship between Kazal-type inhibitors and glycoprotein hormones. PMID- 2226785 TI - Efficient aminoacylation of a yeast tRNA(Asp) transcript with a 5' extension. AB - A yeast aspartic acid tRNA with a 5' extension of 14 nucleotides was obtained by in vitro transcription with T7 DNA dependent RNA polymerase. This transcript, called extended tRNA(Asp) transcript, retains its aspartylation capacity with the same Km and only three times reduced kcat values as compared to those measured for canonical tRNA(Asp). This result indicates that the 5' extension of the amino acid acceptor stem of tRNA(Asp) does not interfere with recognition by aspartyl tRNA synthetase. However, in contrast to the wild-type tRNA(Asp) transcript, the 5' extended molecule presents a reduced capacity to be mischarged by arginyl-tRNA synthetase, suggesting the existence of different structural requirements in aspartyl- and arginyl-tRNA synthetases for tRNA(Asp) recognition. PMID- 2226784 TI - Characterization of muscarinic acetylcholine receptors on the rat pancreatic gastrin-producing cell line B6 RIN. AB - The mechanisms of cholinergic stimulation of gastrin cells were studied in the rat pancreatic cell line B6 RIN. Carbachol induced an increase in intracellular Ca2+ and stimulated gastrin release in a dose-dependent manner over the range 10( 5)-10(-3) M. These effects were completely abolished by atropine, suggesting the implication of muscarinic cholinergic receptors. The binding properties of these receptors were investigated. [N-Methyl-3H]scopolamine [( 3H]NMS) binding on cell homogenates was time-dependent, saturable and consistent with a single high affinity binding class (Kd = 39.5 pM, and Bmax = 7.9 fmol/mg DNA). Carbachol competitively inhibited [3H]NMS binding. The potency of inhibition of [3H]NMS binding by subtype selective antagonists was hexahydrodifenidol greater than pirenzepine greater than AF-DX 116. These results suggest the M3 muscarinic receptors may be involved in the carbachol-induced gastrin release from B6 RIN cells. PMID- 2226786 TI - Purification and site-specific immobilization of genetically engineered glucose dehydrogenase on thiopropyl-Sepharose. AB - The gene encoding glucose dehydrogenase (EC 1.1.1.47) from Bacillus subtilis was inserted in a plasmid 1.0 kb downstream from a lac promoter, resulting in a 70 fold higher production of the enzyme when expressed in Escherichia coli. A glucose dehydrogenase mutant containing a cysteine residue at position 44 could also be expressed at the same high level. This single cysteine residue was used as an 'affinity tag' to simplify the purification procedure as well as for site specific immobilization of glucose dehydrogenase on Thiopropyl-Sepharose. This enzyme was purified to homogeneity with a final recovery of 65% and a specific activity of 240 U/mg. The oriented immobilization resulted in increased thermal stability. PMID- 2226787 TI - Methyllycaconitine: a selective probe for neuronal alpha-bungarotoxin binding sites. AB - The ability of methyllycaconitine (MLA) to inhibit the binding of [125I]alpha bungarotoxin to rat brain membranes, frog and human muscle extracts and the human muscle cell line TE671 has been measured. MLA showed a markedly higher affinity for the rat brain site (Ki 1.4 x 10(-9) M) than for the muscle receptors (Ki 10( 5)-10(-6) M). Structure modelling techniques were used to fit the structure of MLA to a nicotinic pharmacophore model. MLA is the first low molecular weight ligand to be shown to discriminate between muscle nicotinic receptors and their alpha-bungarotoxin-binding counterpart in the brain, and as such may be a useful structural probe for pursuing the structural and functional properties of the neuronal protein. PMID- 2226789 TI - The functional properties of full length and mutant chicken gizzard smooth muscle caldesmon expressed in Escherichia coli. AB - Wild type chicken gizzard caldesmon (756 amino acids) was expressed in a T7 RNA polymerase-based bacterial expression system at a yield of 1 mg pure caldesmon per litre bacterial culture. A mutant composed of amino acids 1-578 was also constructed and expressed. The wild type and mutant caldesmon were purified and compared with native chicken gizzard caldesmon. Native and wild type expressed caldesmon were indistinguishable in assays for inhibition of actin-tropomyosin activation of myosin ATPase, reversal of inhibition by Ca2(+)-calmodulin and binding to actin, actin-tropomyosin, Ca2(+)-calmodulin, tropomyosin and myosin. The mutant missing the C-terminal 178 amino acids had no inhibitory effect and did not bind to actin or Ca2(+)-calmodulin. It bound to tropomyosin with a 5-fold reduced affinity and to myosin with a greater than 10-fold reduced affinity. PMID- 2226788 TI - Adherence of human neutrophils changes Ca2+ signaling during activation with opsonized particles. AB - Changes in the cytosolic free Ca2+ concentration ([Ca2+]i) upon activation of human neutrophils by opsonized particles (serum-treated zymosan; STZ) were evaluated by three different methods: (i) measurement of total fluorescence changes in indo-1 loaded neutrophils activated in suspension; (ii) measurement of fluorescence changes in individual indo-1 loaded neutrophils in a flow cytometer and (iii) measurement of fluorescence changes in individual fura-2 loaded neutrophils adherent to serum-coated coverslips. Our study shows that the opsonized particle-induced change in [Ca2+]i in neutrophils is altered during adherence of the cells to a serum-coated surface. These observations might be of importance for neutrophil function in vivo, since adherence is a prerequisite for diapedesis and chemotaxis. PMID- 2226790 TI - Molecular cloning of human cardiac troponin I using polymerase chain reaction. AB - We have used the polymerase chain reaction (PCR) to synthesise a cDNA encoding part of human cardiac troponin I. Amplification was achieved using fully degenerate sets of oligonucleotides corresponding to conserved regions of amino acid sequence identified in other troponin I isoforms. The cloned PCR fragment was subsequently used to isolate full-length cDNAs from a cardiac cDNA library. We describe the approach, as a general cloning strategy starting from limited amino-acid sequence data and report the cloning, and complete amino acid sequence of human cardiac troponin I. Analysis of human development using these clones demonstrates early expression of this gene in the heart. PMID- 2226791 TI - Site directed mutagenesis of subunit 8 of yeast mitochondrial ATP synthase. Functional and import properties of a series of C-terminally truncated forms. AB - The function of the positively charged C-terminal region of mitochondrially encoded subunit 8 of yeast mitochondrial ATP synthase was investigated using derivatives truncated at each of the 3 positively charged residues (Arg37, Arg42 and Lys47). Each construct, allotopically expressed in the nucleus, was tested for its ability to import and assemble functionally into ATP synthase in yeast cells unable to synthesize mitochondrial subunit 8. The efficiency of import of each construct into isolated wild-type yeast mitochondria was also determined. One construct truncated at the penultimate residue of subunit 8 (Lys47) functions in vivo and shows efficient import in vitro. Thus subunit 8 can function with only two positively charged residues. The remainder of the subunit 8 variants failed to rescue in vivo. Since they all show greatly reduced or undetectable import in vitro, presumably because of the increased hydrophobic character of the subunit 8 moiety in the chimaeric precursors, the status of these variants as regards assembly and function is not clear. PMID- 2226792 TI - Rat lactate dehydrogenase A and B subunit concentrations are not regulated by mRNA abundance in liver and heart. AB - RNA was isolated from rat liver and heart tissues at various times up to 12 weeks after birth, and probed on slot blots with lactate dehydrogenase A and B cDNA probes. Although the relative abundances of LDH A in liver and LDH B in heart increased substantially in the 12 weeks after birth, mRNAs for both isoenzymes remained remarkably stable in both tissues over the same period. The implications of these observations for the regulation of constitutive gene expression are discussed. PMID- 2226793 TI - Inhibition of thrombin by synthetic hirudin peptides. AB - To investigate the role of different regions of hirudin in the interaction with the proteinase thrombin, segments of hirudin containing 15-51 residues were synthesized. The C-terminal segment 40-65 inhibited the fibrinogen clotting activity of thrombin but not amidolysis of tosyl-Gly-Pro-Arg-p-nitroanilide. Central peptide 15-42 was insoluble at pH 7, but peptide 15-65 inhibited fibrinogen clotting and amidolysis to an equal extent. The N-terminal loop peptide 1-15 had no inhibitory activity and did not affect the potency of peptide 15-65. These data suggest that the central region inhibits catalysis. PMID- 2226794 TI - Analysis of beta-tubulin sequences reveals highly conserved, coordinated amino acid substitutions. Evidence that these 'hot spots' are directly involved in the conformational change required for dynamic instability. AB - Vertebrate beta-tubulins have been classified into six classes on the basis of their C-terminal sequences [(1987) J. Cell Biol. 105, 1707-1720]. In particular, the sequences starting at residue 430 differ between isotypes of the same animal but are conserved between species. We extend this analysis and show that there are three 'hot spots', at residues 35, 55-57 and 124 which exhibit intra-species heterogeneity but inter-species conservation. There is a remarkable correlation between the identity of these residues and the C-terminal sequences, and suggests that the vertebrate beta-tubulins fall into three broad types. This correlation extends to those non-vertebrate organisms which have the Type 1 C-terminal sequence. We propose that these three 'hot spots' and the C-terminal peptide interact in the tertiary structure. We have also noted that the C-terminal peptide almost always contains a single phenylalanine or tyrosine residue, and that there is a strong correlation between this residue and the amino acids at positions 217/218, in both the vertebrate and non-vertebrate sequences. We propose that the C-terminal aromatic amino acid interacts with residues 217/218 in the tertiary structure. Analysis of conditions which stabilise microtubules and/or lower the steady state critical concentration strongly suggests that these two sets of coordinated amino acid substitutions are directly involved in effecting the conformational change associated with GTP hydrolysis which results in dynamic instability. We propose that there is an interaction between the highly acidic sequence between residue 430 and the aromatic amino acid (termed peptide A) and conserved basic amino acids located close to the 'hot spots'. We suggest that this interaction is altered in response to the assembly-dependent GTP hydrolysis, with the consequential increase in the subunit dissociation rate constant. PMID- 2226795 TI - Cloning and nucleotide sequence of cDNA for retinochrome, retinal photoisomerase from the squid retina. AB - The Rhodopsin-retinochrome system is essential for the visual photoreception of molluscs. cDNA coding for retinochrome of the squid (Todarodes pacificus) was cloned and the nucleotide sequence has been determined. The sequence (2.1 kb) covers the whole coding region of 903 bp. The deduced primary sequence suggests that retinochrome contains seven transmembrane spanning domains. The homology with bovine rhodopsin and the possible retinal binding site are also discussed. PMID- 2226796 TI - Uni-site ATP synthesis in thylakoids. AB - Uni-site ATP synthesis was measured with thylakoids. The membrane-bound ATP synthase, CF0F1, was brought into the active, reduced state by illumination in the presence of thioredoxin, dithiothreitol and phosphate. This enzyme contains two tightly bound ATP per CF0F1. ATP was released from the enzyme when ADP was added in substoichiometric amounts during illumination. Experiments with [14C]ADP indicated that after binding the same nucleotide was phosphorylated and released as [14C]ATP, i.e. only one site is involved in ATP-synthesis ('uni-site ATP synthesis'). The two tightly bound ATP are not involved in the catalytic turnover. The rate constant for ADP binding was (4 +/- 2) x 10(6) M-1s-1. Compared to deenergized conditions the rate constant for ADP binding and that for ATP-release were drastically increased, i.e. membrane energization increased the rate constants for the ATP-synthesis direction. PMID- 2226798 TI - Analysis of the stop codon context in plant nuclear genes. AB - A region of 18 nucleotides surrounding the stop codon (the stop codon context) in 748 plant nuclear genes was analyzed. Non-randomness was found both upstream and downstream from the stop codon, suggesting that these sequences may help in ensuring efficient termination of translation. The UAG amber codon is the least used stop codon and the bias in the nucleotide distribution 5' and 3' to the stop codon was more pronounced for the amber codon than for the other stop codons. This might indicate that the codon context affects termination more at UAG than at UGA or UAA stop codons. PMID- 2226797 TI - Carbohydrate structures of a human tissue plasminogen activator variant expressed in recombinant Chinese hamster ovary cells. AB - The carbohydrate structures of a genetically engineered human tissue plasminogen activator variant bearing a single N-glycosylation site at Asn 448 are reported. After isolation of the tryptic glycopeptide and liberation of the N-linked carbohydrates by polypeptide:N-glycosidase F, 6 major oligosaccharide fractions were separated by HPLC on NH2-bonded phase. Their structures were determined by compositional and methylation analyses combined with fast atom bombardment mass spectrometry. Seventy percent of the carbohydrates were of the biantennary complex type with fucose at the proximal GlcNAc and zero, one or two alpha 2-3 linked NeuAc. The remainder were triantennary structures with one, two or three NeuAc. PMID- 2226799 TI - Nonthermal 60 Hz sinusoidal magnetic-field exposure enhances 45Ca2+ uptake in rat thymocytes: dependence on mitogen activation. AB - The effect of a 60 Hz sinusoidal magnetic field of nonthermal intensity on Ca2+ metabolism in rat thymic lymphocytes (thymocytes) was assessed in resting cells and in cells activated with the mitogen Concanavalin A (Con A). A 60 min exposure at 37 degrees C to an induced electric field of 1.0 mV/cm produced an average 2.7 fold increase in Con A-dependent 45Ca2(+)-uptake compared to non-exposed, isothermal control cells. In contrast, 45Ca2+ uptake remained unaltered during exposure of resting thymocytes. It was also found that thymocytes with a diminished ability to mobilize Ca2+ in response to Con A were most sensitive to the 60 Hz magnetic field. Although the precise mechanism of field interaction is at present unknown, modulation of Ca2+ metabolism during cell activation may represent a common pathway for field coupling to cellular systems. PMID- 2226800 TI - Membrane lateral pressure as a modulator of glycerol-3-phosphate dehydrogenase activity. AB - Michaelis-Menten kinetics of glycerol-3-phosphate dehydrogenase activity in proteoliposomes from brown adipose tissue mitochondria with exogenously added phospholipids or cholesterol was measured. It was shown that changes in membrane lipid composition affected the membrane lateral pressure and therefore modulated the enzyme activity, namely Vmax value. Contrarily, changes in surface charge caused by minute amounts of phosphatidylserine or charged organic substances influenced only the apparent Km value. The role of bulk phospholipids in regulation of glycerol-3-phosphate dehydrogenase is discussed. PMID- 2226801 TI - Primary structure and functional expression from cDNA of the cardiac ryanodine receptor/calcium release channel. AB - The sequence of 4968 (or 4976 with an insertion) amino acids composing the ryanodine receptor from rabbit cardiac sarcoplasmic reticulum has been deduced by cloning and sequencing the cDNA. This protein is homologous in amino acid sequence and shares characteristic structural features with the skeletal muscle ryanodine receptor. Xenopus oocytes injected with mRNA derived from the cardiac ryanodine receptor cDNA exhibit Ca2(+)-dependent Cl- current in response to caffeine, which indicates the formation of functional calcium release channels. RNA blot hybridization analysis with a probe specific for the cardiac ryanodine receptor mRNA shows that the stomach and brain contain a hybridizable RNA species with a size similar to that of the cardiac mRNA. This result, in conjunction with cloning and analysis of partial cDNA sequences, suggests that the brain contains a cardiac type of ryanodine receptor mRNA. PMID- 2226802 TI - Protective role of CaCl2 against Pb2+ inhibition in Photosystem II. AB - The Pb2+ treatment of Photosystem II (PS II) membrane fragments, either intact or depleted in 17 and 23 kDa extrinsic polypeptides, inhibits PS II activity. When CaCl2 was present in the assay, the Pb2+ inhibition was significantly reduced in both types of PS II membranes, suggesting a protective role of CaCl2 against Pb2+ inhibition. However, in either case, the degree of PS II inhibition by Pb2+ was higher in the protein depleted than in intact PS II. It showed that the loss of endogenous Ca2+ induced by polypeptide depletion causes the PS II to be more susceptible to Pb2+. The interaction of Pb2+ with CaCl2 in protein-depleted PS II was competitive. Our results suggest that Pb2+ competes for binding to the Ca2(+) and Cl- active sites in the water-splitting complex. Since Pb2+ inhibition of PS II activity cannot be reversed by CaCl2 but can be reversed by diphenylcarbazide, we conclude that Pb2+ induced inhibition of PS II activity was mediated via the water-splitting system. PMID- 2226803 TI - The RNA component of RNase P in Schizosaccharomyces species. AB - In the fission yeast Schizosaccharomyces pombe, the enzyme RNAse P copurifies with two RNAs, K1- and K2-RNA, which are identical except for their termini [1] and which are encoded by a single gene [2]. We have undertaken the cloning of the K-RNA genes in related organisms in order to gain comparative structural information. Because the K-RNA sequence is poorly conserved across species, we have cloned the K-RNA genes in the Schizosaccharomyces species S. malidevorans, S. japonicus, S. versatilis, and S. octosporus. Of the 4 species, only S. octosporus contains a K-RNA gene different from that in S. pombe; the gene diverges by 20%. Based on the two sequences, nuclease protection data and computer analysis, we have proposed a secondary structure model for the K-RNA. Northern analysis shows the K-RNA genes in all four Schizosaccharomyces species to be expressed as two RNAs, as in S. pombe. PMID- 2226804 TI - Structural features of the McPC603 Fab fragment not defined in the X-ray structure. AB - The proteolytic Fab fragment of the well characterized antibody McPC603 was compared to the recombinant Fab fragment, which was obtained in functional form from an Escherichia coli expression system [(1989) Methods Enzymol. 178, 497 515]. We found evidence that the proteolytic fragment is glycosylated at Asn H160 in the CH1 domain, where additional electron density had been observed in the crystal structure [J. Mol. Biol. 190, 593-604]. In addition, its heavy chain is about 30 amino acids longer than visible in the electron density and thus contains the complete hinge region. These structural differences between the recombinant Fab fragment, which had been designed exactly according to the defined electron density, and the proteolytic Fab fragment of McPC603 had no effect on the hapten binding properties of these antigen binding fragments. Yet, it may be important to be aware of these structural features of McPC603 in folding studies and some comparative analyses of antibody structures. PMID- 2226805 TI - Reaction mechanism of oxidative rearrangement of flavanone in isoflavone biosynthesis. AB - Microsomes that were prepared from elicitor-treated Pueraria lobata cell cultures catalyzed the conversion of liquiritigenin, a flavanone, into daidzein, an isoflavone. The reaction was resolved into two steps. 2, 7, 4' Trihydroxyisoflavonone was formed as a major product when liquiritigenin was incubated with carefully washed microsomes in the presence of NADPH. The structure of 2, 7, 4'-trihydroxyisoflavanone was confirmed by mass and 1H NMR spectroscopies. The enzyme responsible for this rearrangement reaction is a cytochrome P-450-dependent monooxygenase. Upon treatment with a soluble enzyme fraction 2, 7, 4'-trihydroxyisoflavone yielded daidzein quantitatively. The incorporation of 18O from 18O2 into the 2-hydroxy group of 2, 7, 4' trihydroxyisoflavanone was demonstrated by the shift of molecular ion in its mass spectrum. Based on these observations a new reaction mechanism, hydroxylation associated with 1,2-migration, is proposed for the oxidative rearrangement reaction catalyzed by the cytochrome P-450 enzyme of Pueraria lobata. PMID- 2226806 TI - High-affinity binding of a synthetic heptaglucoside and fungal glucan phytoalexin elicitors to soybean membranes. AB - Soybean membranes possess high-affinity binding sites for fungal beta-glucans that elicit phytoalexin synthesis. The ability of 1,3-1,6-beta-glucans, released by acid hydrolysis from mycelial walls of Phytophthora megasperma f.sp. glycinea, to compete for the putative phytoalexin elicitor receptors increases with their average degree of polymerization (DP). The results suggest a function where the probability for glucan fragments of containing a structural determinant that is optimal for binding approaches 1 as the DP tends to infinity. Ligand displacement data obtained against a 125I-labeled glucan elicitor (average DP = 18) provided a theoretical minimum IC50 (50% inhibitory concentration) for 1,3-1,6-beta-glucans of 3 nM. The IC50 value obtained for a synthetic hepta-beta-glucoside having a known elicitor-active structure was 8 nM, remarkably close to the predicted value. Displacement of the 125I-glucan of large DP was uniform and complete showing that the heptaglucoside had access, with similar affinity, to all sites available to the radioligand. Further analysis using a 125I-labeled aminophenethylamine derivative of the heptaglucoside suggested that the putative glucan-elicitor receptors bind a basic structural determinant present in all elicitor-active glucans from the soybean pathogen P. megasperma. PMID- 2226807 TI - Newly identified type of beta actin reduces invasiveness of mouse B16-melanoma. AB - Low metastatic parent B16 melanoma and isolated B16-F1 cell lines have a third actin designated as beta m(Ax:previously). beta m actin is scantily or not at all detected in highly metastatic cell lines, such as B16-F10 and BL6. To directly assess the physiological role of beta m in phenotypic changes of B16 melanoma, we transfected expression plasmids of beta m into B16-F10 cells. The actin expressed in the transfectants is located largely in cytoskeletal fractions. The transfectants exhibited a larger number of stress fibers and a lower invasiveness than did the recipient cells. Thus, beta m actin plays an important role in the organization of actin stress fibers, the result being a decrease in invasiveness of B16 melanoma. PMID- 2226808 TI - Prenyltransferase compartmentation in cells of Vitis vinifera cultivated in vitro. AB - Two prenyltransferases were located in cell cultures of Vitis vinifera. A geranyl pyrophosphate synthase (EC 2.5.1.1) was associated with plastid-like membranes whereas a farnesyl pyrophosphate synthase (EC 2.5.1.10) was found to be soluble. PMID- 2226809 TI - A stereospecific enzyme of the putative biosynthetic pathway of cardenolides. Characterization of a progesterone 5 beta-reductase from leaves of Digitalis purpurea L. AB - Leaves of Digitalis purpurea contain an enzyme activity which catalyzes the conversion of progesterone to 5 beta-pregnane-3,20-dione. Since cardenolides without exception possess a 5 beta-configuration, 5 beta-pregnane-3,20-dione can serve as a precursor for this class of secondary metabolites. It is assumed that the enzyme is part of the putative biosynthetic pathway of cardenolides. This enzyme activity was spotted in the soluble fraction of a crude homogenate. Product formation was detected by gas chromatography and by gas chromatography/mass spectroscopy (g.c./m.s.). The enzyme had a pH optimum at 8.0 and an apparent Km value of 6 microM for progesterone. It required NADPH as a co substrate with an apparent Km value of 22 microM. The optimum temperature in vitro was 30 degrees C. The activity was not dependent on monovalent and bivalent cations. PMID- 2226811 TI - Characterization of the virA gene of the agropine-type plasmid pRiA4 of Agrobacterium rhizogenes. AB - We sequenced a 4.2-kb DNA region encompassing the vir A locus of the hairy-root inducing plasmid pRiA4, and compared its sequence with the published vir A region sequences of four tumor-inducing plasmids. An open reading frame capable of coding for 829 amino acids was identified for vir A. Deletion mutants of vir A constructed by fusing to lacZ, but not the wild-type game itself, were efficiently expressed in Escherichia coli when they were put downstream front the lac promoter. These fused gene products became soluble or insoluble depending on the length of their lacZ moieties. PMID- 2226810 TI - Function of the conserved triad residues in the class C beta-lactamase from Citrobacter freundii GN346. AB - The conserved KTG triad in the class C beta-lactamase from Citrobacter freundii GN346 was examined as to its function by means of site-directed mutagenesis. The following conversions were performed; Lys-315 to arginine, alanine or glutamic acid, Thr-316 to valine, and Gly-317 to alanine, proline or isoleucine. The resultant mutant enzymes revealed that a basic amino acid at position 315 and a small uncharged residue at position 317 are essential for the enzyme activity, but a hydroxyl group at residue 316 is not required for the enzymatic catalysis. The kinetic properties of the purified Arg-315 and Val-316 enzymes provided information on the function of these residues. PMID- 2226812 TI - Possible mechanism of nuclear translocation of proteasomes. AB - Proteasomes (multicatalytic proteinase complexes), which are identical to the ubiquitous eukaryotic 20S particles, are localized in both the cytoplasm and the nucleus, but the mechanism of their co-localization in the two compartments is unknown. On examination of the primary structures of subunits of proteasomes, a consensus sequence for nuclear translocation of proteins, X-X-K-K(R)-X-K(R) (where X is any residue), was found to be present in some subunits and to be highly conserved in the subunits of a wide range of eukaryotes. In addition, proteasomal subunits were found to bear a cluster of acidic amino acid residues and also a potential tyrosine phosphorylation site that was located in the same polypeptide chain as the nuclear location signal. These structural properties suggest that two sets of clusters with positive and negative charges serve to regulate the translocation of proteasomes from the cytoplasm to the nucleus, and that phosphorylation of tyrosine in certain subunits may play an additional role in transfer of proteasomes into the nucleus. PMID- 2226813 TI - The primary structure of rat ribosomal protein S7. AB - The amino acid sequence of the rat 40S ribosomal subunit protein S7 was deduced from the sequence of nucleotides in two recombinant cDNAs and confirmed from the amino acid sequence of a cyanogen bromide peptide obtained from the protein. Ribosomal protein S7 has 194 amino acids and has a molecular mass of 22,113. Hybridization of the cDNA to digest of nuclear DNA suggests that there are 14-16 copies of the S7 gene. The mRNA for the protein is about 725 nucleotides in length. Rat S7 is homologous with Xenopus laevis S8. The protein contains a possible internal duplication of 10 residues. PMID- 2226814 TI - Multiple mechanisms of protein kinase C inhibition by triphenylacrylonitrile antiestrogens. AB - The activation of type I (gamma), II (beta) and III (alpha) protein kinase C (PKC) subspecies by phosphatidylserine (PS) and diacylglycerol (DAG) is inhibited by micromolar concentrations of triphenylacrylonitrile (TPE) antiestrogens. TPE A (with p-hydroxy and p-diethylaminoethoxy groups on the 3- and 3'-phenyl rings, respectively) interacts with PS-vesicles as well as with the regulatory domain of PKC, probably at a site different from the Ca2+ and DAG binding sites. The interaction of TPE A with the regulatory domain of enzyme is very slow. Apparently, TPE A does not interact with the catalytic domain of PKC. In contrast, another TPE derivative, TPE B (with a p-hydroxy group on each of the three phenyl rings) inhibits the enzyme activity in a competitive manner with respect to ATP, suggesting that this TPE interacts with the catalytically active site of the enzyme. It seems likely that various TPE antiestrogen derivatives may exert their inhibitory action on PKC by multiple different mechanisms. PMID- 2226815 TI - Transcriptional and post-transcriptional suppression of P450IIC11 and P450IIC12 by inflammation. AB - Induction of inflammation in rats by treatment with endotoxin or turpentine is known to suppress levels of hepatic mRNAs for P450IIC11 and P450IIC12. We report that transcription of CYP2C12 in female rats is not significantly reduced from control levels; suppression of this gene during inflammation appears to be mediated post-transcriptionally. In contrast, transcription of CYP2C11 in male rats is reduced to 23% and to 5% of control levels by turpentine and by endotoxin, respectively. Sex-specificity of CYP2C11 expression is also regulated transcriptionally, whereas sex-specificity of CYP2C12 expression appears to be regulated by a post-transcriptional mechanism. PMID- 2226816 TI - Purification and characterization of a tartrate-sensitive acid phosphatase of Trypanosoma brucei. AB - In search for invariant surface proteins in Trypanosoma brucei bloodstream forms, acid phosphatase was investigated. Earlier work had shown that part of the cellular phosphatase activity is associated with the flagellar pocket of the parasite. It is demonstrated that T. brucei contains at least two membrane-bound enzymes, one is sensitive to the inhibitor L-(+)-tartrate while the other is resistant. The tartrate-sensitive phosphatase was purified to homogeneity by monoclonal antibody affinity chromatography and shown to be a glycoprotein of low abundance (13,000 molecules/cell). It has an apparent molecular weight of 70,000 Da. The usefulness of acid phosphatase as a marker for characterizing the membrane lining the flagellar pocket is discussed. PMID- 2226818 TI - Hydrodynamic data show that C1- inhibitor of complement forms compact complexes with C1-r and C1-s. AB - The C1- inhibitor of the complement cascade forms stoichiometric complexes with C1-r and C1-s and controls the activation of first component C1 of complement. Literature sedimentation coefficients s degrees 20,w for the complexes formed between C1- inhibitor, C1-r and C1-s were analysed using frictional ratios and the hydrodynamic sphere approach. A head-and-tail two-domain model for C1- inhibitor was combined with cylindrical hydrodynamic models for the six-domain structures of C1-r and C1-s. The hydrodynamic data show that the heavily glycosylated N-terminal domain of C1- inhibitor is positioned close to the two complement 'short consensus repeat' domains found in the centre of C1-r and C1-s. PMID- 2226817 TI - Synthetic sialyl glycolipids (sialo-cholesterol and sialo-diglyceride) induce granulocytic differentiation of human myelogenous leukemia cell line HL-60. AB - When HL-60 cells were cultivated with synthetic sialyl glycolipids, sialo cholesterol and sialo-diglyceride, the cells were found to be differentiated into mature granulocytes on morphological and functional criteria. The differentiation of cells was accompanied by inhibition of cell proliferation. The differentiation inducing activity of sialo-cholesterol was greater than that of sialo-diglyceride on a molar basis, and the alpha-anomer of each compound was more potent than the beta-anomer, suggesting that the stereospecific structure of the compounds is important for the differentiation-inducing activity. PMID- 2226819 TI - Could domain movements be involved in the mechanism of trypsin-like serine proteases? AB - It is hypothesised that the characteristic twin domain structure of serine proteases permits important allosteric responses in the molecule when peptide and protein substrates bind. Such movement would be ideal for stressing the scissile bond in the substrate, thereby making the task of hydrolysis substantially easier. The control of the domain movement can be closely associated with substrate binding, via the N- and C-terminal regions of the enzyme. The hypothesis also suggests that certain inhibitory peptides exert their effect by binding without inducing the domain movement. PMID- 2226820 TI - The N intermediate of bacteriorhodopsin at low temperatures: stabilization and photoconversion. AB - In aqueous suspensions of purple membranes (pH 10.2, 0.4 M KCl) an intermediate having an absorption maximum at 570-575 nm (at -196 degrees C) was produced by first heating the M intermediate up to -30 degrees C and then stabilizing it by subsequent cooling to -60 degrees C. We suggest that this species is the intermediate N (or P or R) found and characterized earlier near room temperature. Upon illumination at -196 degrees C N is transformed into a bathochromically absorbing species KN which has an absorption maximum near 605 nm and an extinction 1.35 times that of N. This light reaction is photoreversible. The quantum yield ratio for the forward and back reaction is 0.18 +/- 0.02. The maximum photo steady state concentration of KN is about 0.24. The N intermediate was also trapped in water suspensions of purple membranes at neutral pH and low salt concentration by illumination at lambda greater than 620 nm during cooling. In addition to N another intermediate absorbing in the red (maximum at 610-620 nm) was accumulated in smaller amounts. It is not photoactive at -196 degrees C and apparently is the O intermediate or a photoproduct of N. PMID- 2226821 TI - Conformational changes in human fibrinogen after in vitro phosphorylation and their relation to fibrinogen behaviour. AB - The far-ultraviolet circular dichroism spectra of fibrinogens phosphorylated by protein kinase C or casein kinase II indicated a conformational change corresponding to an increase in ordered secondary structure. The spectra of protein kinase A- or casein kinase I-phosphorylated fibrinogens did not differ substantially from the control. Fluorescence studies indicated changes in the tertiary structure around tryptophan residues for protein kinase A- or C phosphorylated fibrinogens, but failed to show any such change for fibrinogen phosphorylated by either of the casein kinases. This latter result was also confirmed by circular dichroism measurements in the near-ultraviolet region. The apparent increase in ordered structure was proposed as an explanation for the slower rate of plasmin degradation seen in fibrinogens after phosphorylation by protein kinase C [6], and casein kinase II, especially as both spectral changes and plasmin degradation rate were unaffected by alkaline phosphatase. PMID- 2226822 TI - Synthesis of a trihexacontapeptide corresponding to the sequence 8-70 of eglin c and studies on the relationship between the structure and the inhibitory activity against human leukocyte elastase, cathepsin G and alpha-chymotrypsin. AB - A trihexacontapeptide corresponding to the sequence 8-70 of eglin c and its related peptides were synthesized by the conventional solution method and their inhibitory activity against human leukocyte elastase, cathepsin G and alpha chymotrypsin was examined. Although synthetic eglin c (41-49) inhibited cathepsin G and alpha-chymotrypsin (Ki = 4.0 x 10(-5) M and 2.0 x 10(-5) M, respectively) but not leukocyte elastase, the synthetic trihexacontapeptide potently inhibited cathepsin G, alpha-chymotrypsin and leukocyte elastase (Ki = 1.8 x 10(-9) M, 1.4 x 10(-9) M and 2.2 x 10(-9) M, respectively). The relationship between the structure of eglin c and the inhibitory activity against the above enzymes is also described. PMID- 2226823 TI - Luminol enhanced chemiluminescence of the perfused rat heart during ischemia and reperfusion. AB - We show that the production of Luminol reactive oxygen radicals in the perfused rat heart under ischemia and reperfusion can be monitored continuously by measuring the chemiluminescence of Luminol-perfused hearts. Luminol did not affect the monitored physiological parameters of the hearts. Chemiluminescence increased during ischemia and reperfusion. Superoxide dismutase treatment of the heart before ischemia, but not catalase, abolished these increases. PMID- 2226824 TI - The primary structure of iodopsin, a chicken red-sensitive cone pigment. AB - A purified iodopsin was digested by CNBr or several proteolytic enzymes into fragments, the amino acid sequences of which were determined. A partial sequence of the C-terminal fragment was utilized for synthesizing an oligonucleotide probe which identified the iodopsin cDNA (1339 bases). The deduced amino acid sequence (362 residues) had 80%, 42%, or 43% homology to that of human red-sensitive cone pigment, cattle or chicken rhodospin, respectively. Although the hydropathy profile implies that iodopsin, like rhodopsin, has 7 transmembrane alpha-helical segments, iodopsin may have a hydrophilic pocket near the seventh segment on the basis of the unexpected cleavages in the middle of the segment VII by chymotrypsin under nondenaturing conditions. PMID- 2226825 TI - The actin gelling activity of chicken gizzard alpha-actinin at physiological temperature is triggered by water sequestration. AB - At 37 degrees C, in the presence of 6% (w/v) polyethylene glycol 6000, 30 nM alpha-actinin from chicken gizzard induces the gelation of 12 microM actin. Static measurement shows that the addition of 30 nM alpha-actinin increases the rigidity of the system from 23.5 to 54 dynes/cm2. According to the theory of osmoelastic coupling, also large additives, such as the proteins of the cell sap, are able to cause an osmotic stress equivalent to that caused by polyethylene glycol. We thus conclude that, in vivo, alpha-actinin acts as an actin gelling protein. PMID- 2226826 TI - Heterogeneity of metabolic response to muscular exercise in humans. New criteria of invariance defined by in vivo phosphorus-31 NMR spectroscopy. AB - 31P NMR spectroscopy at 4.7 T has been used in vivo to follow metabolic changes associated with exercise and subsequent recovery in the forearm flexor digitorum superficialis muscle of 14 healthy volunteers. The muscle content in phosphomonoesters at rest provides an index of glycogenolytic activity. Quantitative linear correlations have been shown to link end-of-exercise acidosis to recovery kinetics of phosphocreatine and phosphocreatine/organic phosphate ratio. These linear relationships constitute new metabolic invariants to be used in the study of myopathies and muscle adaptation to exercise. PMID- 2226827 TI - Spin-spin relaxation of the phosphodiester resonance in the 31P NMR spectrum of human brain. The determination of the concentrations of phosphodiester components. AB - The phosphodiester peak in 31P nuclear magnetic resonance spectra of human brain in vivo is often the most prominent feature of the spectrum. We have demonstrated that this resonance exhibits bi-exponential spin-spin relaxation, giving relaxation times of 2 and 10 ms. We interpret this in terms of the two components which make up the peak, bilayer lipids and the small cytosolic phosphates glycerophosphoethanolamine and glycerophosphocholine. Using the relaxation times and the relative peak heights of the two components we have also been able to quantitate the concentration of the bilayer lipids as 20-40 times that of ATP. PMID- 2226829 TI - Transient versus steady state NOE in paramagnetic molecules Cu2Co2SOD as an example. AB - Truncated, steady state and transient NOE experiments have been performed on bovine Cu2Co2 superoxide dismutase. The effectiveness of the different NOE experiments in the general case of paramagnetic macromolecules is discussed. It is concluded that steady state NOEs give superior results. The validity of the two spins approximation is discussed, and NOE values for a fully coupled set of nuclei have been calculated. Transient NOE experiments, when properly performed, confirm the previous assignment of the hyperfine shifted signals in Cu2Co2SOD based on steady state NOE measurements [(1989) Inorg. Chem. 28, 4650] and eliminate any further reason for controversy on an important issue as the assignment of the 1H NMR signals of protons of metal-coordinated imidazoles. PMID- 2226828 TI - Hoogsteen versus Watson-Crick A-T basepairing in DNA complexes of a new group of 'quinomycin-like' antibiotics. AB - The interaction of a new group of 'quinomycin-like' antibiotics with the DNA duplexes d(ACGT)2 and d(GACGTC)2 has been investigated in solution by 1H NMR spectroscopy. By monitoring the intensity of intranucleotide base H6/H8 to deoxyribose H1'NOE cross-peaks we conclude that the terminal A-T basepairs flanking the CG bisintercalation site in the d(ACGT)2 complex adopt the Hoogsteen bonding scheme, with the purine base in a syn conformation. By comparison in the d(GACGTC)2 complex all glycosidic bond angles are anti, consistent with a preferred Watson-Crick basepairing scheme. Both DNA duplexes appear to be significantly unwound compared with the ligand-free DNAs. The data illustrate the influence of helical constraints on the stability of the Hoogsteen bonding scheme adjacent to the drug binding sites. PMID- 2226830 TI - Highly selective affinity labeling of the primer-binding site of E. coli DNA polymerase I. AB - Highly selective affinity labeling of the primer site of E. coli DNA polymerase I was performed with the 5'-reactive derivatives of oligothymidylate in the presence of poly(dA) template. Subtilysine cleavage proved that the site of affinity modification belonged to the 'Klenow' part of DNA polymerase I. If taken separately, Klenow fragment was not labeled by these oligonucleotide derivatives. The site of affinity labeling were tested in the structure of DNA polymerase I by hydroxylamine cleavage. At least two sites of labeling were revealed. The main one was localized between Gly-833 and His-928. PMID- 2226831 TI - Carboxyatractylate-sensitive uncoupling in liver mitochondria from ground squirrels during hibernation and arousal. AB - Energy coupling parameters of liver mitochondria from hibernating and arousing ground squirrels have been studied. In the oligomycin-treated mitochondria, carboxyatractylate, an inhibitor of the ATP/ADP-antiporter, is shown to decrease the respiration rate, to increase the membrane potential and to lower the rate of the membrane-potential discharge after the addition of cyanide to liver mitochondria from hibernating and arousing animals. BSA effectively substitutes for carboxyactactylate so that carboxyactactylate, added after BSA, has no effect. In mitochondria from hibernating animals, the maximal respiration rate in the presence of DNP and the rate of the membrane potential discharge in its absence are much lower than in those from arousing animals. It has been concluded that upon arousal of the animals from hibernation, the uncoupling of oxidative phosphorylation, mediated by free fatty acids and ATP/ADP-antiporter, parallels the respiratory chain activation. PMID- 2226833 TI - The primary structure of superoxide dismutase purified from anaerobically maintained Bacteroides gingivalis. AB - The superoxide dismutase (SOD) of Bacteroides gingivalis can use either iron or manganese as a cofactor in its catalytic activity. In this study, the complete amino acid sequence of this SOD purified from anaerobically maintained B. gingivalis cells was determined. The proteins consisted of 191 amino acid residues and had a molecular mass of 21,500. The sequence of B. gingivalis SOD showed 44-51% homology with those for iron-specific SODs (Fe-SODs) and 40-45% homology with manganese-specific SODs (Mn-SODs) from several bacteria. However, this sequence homology was considerably less than that seen among the Fe-SOD (65 74%) or Mn-SOD family (42-60%). This indicates that B. gingivalis SOD, which accepts either iron or manganese as metal cofactor, is a structural intermediate between the Fe-SOD and Mn-SOD families. PMID- 2226832 TI - Amino acid sequence of CAP37, a human neutrophil granule-derived antibacterial and monocyte-specific chemotactic glycoprotein structurally similar to neutrophil elastase. AB - We report the amino acid sequence of CAP37, a human neutrophil granule protein with antibacterial and monocyte-specific chemotactic activity. CAP37 is a single chain protein consisting of 222 amino acid residues. It has three N-glycosylation sites, at Asn residues 100, 114 and 145. Some species of CAP37 are glycosylated at all three sites; some at Asn-114 alone, others at Asn-114 and Asn-110 or Asn 145. CAP37 has 45% sequence identity to human neutrophil elastase, and 30-37% identity to several other granule serine proteinases. Despite these similarities, CAP37 is not a serine proteinase because the active site residues serine and histidine are replaced. PMID- 2226834 TI - Characterization of the beta-chain N-terminus heterogeneity and the alpha-chain C terminus of human platelet GPIIb. Posttranslational cleavage sites. AB - Human platelet glycoprotein IIb (GPIIb) and IIIa (GPIIIa) form a Ca2(+)-dependent heterodimer, the integrin GPIIb/IIIa, which functions as the fibrinogen receptor at the surface of activated platelets. GPIIB and GPIIIa are synthesized as single polypeptides from single messages and their amino acid sequences were derived from their cDNAs. The GPIIb precursor is proteolytically processed to yield the known disulphide-bonded two-chain (GPIIb alpha and GPIIb beta) covalent structure found in mature GPIIb. Our present protein chemical and mass spectrometric analyses indicate that the GPIIb precursor is proteolytically cleaved at two or three sites, to give rise to an homogeneous alpha-chain (GPIIb 1-856) single disulphide-bonded to one of the two beta-chains, which are present in a nearly 1:1 ratio: GPIIb beta 1 (860-1008), with pyroglutamic acid as its blocked N terminal residue: and GPIIb beta 2 (872-1008), with the already known N-terminal sequence. These results satisfy the previously observed electrophoretic size residue: and GPIIb beta 2 (872-1008), with the already known N-terminal sequence. These results satisfy the previously observed electrophoretic size-heterogeneity of the beta-chain, confirmed the potential cleavage sites in the junction region, and indicate a probable dual proteolytic processing of GPIIb, which may be relevant to the rest of the two-chain alpha-subunits of the integrin family. PMID- 2226835 TI - Importance of the G27-A43 mismatch at the anticodon stem of Escherichia coli tRNA(Thr2). AB - The tRNA(Thr2) isoacceptor of E. coli has a G-A mismatch at positions 27-43. When the anticodon of this tRNA was converted to an amber anticodon (CUA), this tRNA showed suppressor activity in E. coli. Moreover, introduction of the base pair (G C or U-A) at positions 27-43 of this suppressor tRNA reduced its suppressor activity. These results indicate that the G27-A43 mismatch is necessary for full function of tRNA(Thr2). PMID- 2226836 TI - The carboxyl terminus heptapeptide of the R2 subunit of mammalian ribonucleotide reductase inhibits enzyme activity and can be used to purify the R1 subunit. AB - The heptapeptide, FTLDADF, identical in sequence to the last seven amino acid residues of the carboxyl terminus of the R2 subunit of mouse ribonucleotide reductase (RR), and its N alpha-acetyl derivative both inhibit calf thymus RR. The N alpha-acetyl derivative is considerably more potent, displaying a K1 of 20 microM. The same K1 was found for N-AcFTLDADF inhibition of a reconstituted ribonucleotide reductase from calf thymus R1 and mouse R2, indicating that the C termini of calf R2 and mouse R2 might be identical. Our results, taken together with previous results of others on inhibition of viral RR, suggest that inhibition of RRs by peptides mimicking the C-terminus of R2 may be a general phenomenon. In addition, we have shown that an affinity column, FTLDADF-Sepharose 4B, can be used to prepare approximately 95% pure calf thymus R1, devoid of contamination with R2, in a very simple procedure that should be generally applicable to R1 purification from many sources. PMID- 2226837 TI - Isolation and characterization of human reg protein produced in Saccharomyces cerevisiae. AB - reg was originally identified as a gene expressed during the regeneration of insulin-producing pancreatic beta-cells of the rat. We built an expression vector containing human reg cDNA to drive Saccharomyces cerevisiae to synthesize the reg protein, and purified it from the culture medium. The 144-amino acid sequence of the recombinant protein was consistent with that deduced from the cDNA and genomic DNA sequence except that the signal sequence of 22 amino acids was eliminated, and the amino-terminal residue of the protein was pyroglutamic acid. The secondary structure of the reg protein was predicted by determination of the intramolecular cystine linkage and of alpha-helix and beta-sheet contents. PMID- 2226839 TI - Depression of prothymosin alpha production in murine thymus correlates with staphylococcal enterotoxin-B-induced immunosuppression [corrected]. AB - Prothymosin alpha [corrected] (ProT alpha) and thymosin beta 4 [corrected] (T beta 4) were isolated from murine thymus and characterized by microsequence analysis. Murine T beta 4 has an identical sequence to bovine T beta 4, whereas murine ProT alpha is highly homologous to rat Pro T alpha. Murine Pro T alpha differs from rat Pro T alpha at two positions, Glu100 and Asp108 of the rat sequence are substituted by aspartic and glutamic acid, respectively, in murine Pro T alpha. The amount of Pro T alpha in murine thymus was found to be reduced after in vivo treatment with staphylococcal enterotoxin B [corrected] (SEB), a superantigen which stimulates T cells bearing specific V beta receptors. Results from the anti-SRBC (sheep erythrocyte) plaque-forming cell assay showed that the antibody response of the spleen cells from these animals was also suppressed. On the other hand, the amount of T beta 4 was not changed significantly. Our studies suggest that the suppression of SEB on antibody response correlates with the depression of Pro T alpha production in the thymus. PMID- 2226838 TI - Biosynthesis of cyclic 2,3-diphosphoglycerate. Isolation and characterization of 2-phosphoglycerate kinase and cyclic 2,3-diphosphoglycerate synthetase from Methanothermus fervidus. AB - Starting from 2-phosphoglycerate the biosynthesis of cDPG comprises two steps: (i) the phosphorylation of 2-phosphoglycerate to 2,3-diphosphoglycerate and (ii) the intramolecular cyclization to cyclic 2,3-diphosphoglycerate. The involved enzymes, 2-phosphoglycerate kinase and cyclic 2,3-diphosphoglycerate synthetase, were purified form Methanothermus fervidus. Their molecular and catalytic properties were characterized. PMID- 2226841 TI - Primary structure of NADP-dependent malic enzyme in the dicotyledonous C4 plant Flaveria trinervia. AB - The primary structure of NADP-dependent malic enzyme (NADP-ME) of the dicotyledonous C4 plant Flaveria trinervia was determined from sequence analysis of a cDNA clone containing the complete coding region. Comparison of the mature F. trinervia NADP-ME with the maize enzyme reveals extensive sequence similarity. In contrast, no significant similarity can be detected between the putative transit peptides of the two enzymes. This suggests that the corresponding parts of the genes arose independently from each other during evolution of mono- and dicotyledonous C4 plants. PMID- 2226842 TI - Molecular cloning, nucleotide sequence and expression of the gene encoding prepro polygalacturonaseII of Aspergillus niger. AB - PolygalacturonaseII of Aspergillus niger was fragmented using CNBr and the NH2 terminal fragment and another fragment were partially sequenced. The polygalacturonaseII (pgaII) gene was then isolated by using an oligonucleotide mixture based on the internal amino acid sequence as a probe. The nucleotide sequence of the pgaII structural gene was determined. It was found that polygalacturonaseII is synthesized as a precursor having an NH2-terminal prepro sequence of 27 amino acids. The cloned gene was used to construct polygalacturonaseII over-producing A. niger strains. PolygalacturonaseII was isolated from one such strain and was determined to be correctly processed and to be fully active. PMID- 2226840 TI - The predicted molecular structure suggests that CTF/NF-I may function as a histone acetylase. AB - The primary structure of nuclear factor-I (CTF/NF-I), a eukaryotic regulatory DNA binding protein involved in both DNA replication and gene transcription, and the secondary structure predictable from it, are compared here with those of a number of prokaryotic acetylases. Hydropathy and Chou-Fasman analyses reveal that the polypeptide chain of CTF/NF-I is likely to fold to higher order structures similar to those of the acetylases, and significant conservation of functionally important regions of the acetylases is observed in CTF/NF-I. It is therefore suggested that CTF/NF-I may function as a histone acetylase. PMID- 2226843 TI - Synergy between zinc and phorbol ester in translocation of protein kinase C to cytoskeleton. AB - Protein kinase C was measured in the cytoskeletal fraction of lymphocytes, platelets and HL60 cells, by specific binding of [3H]phorbol dibutyrate and by immunoblotting with antibody to a consensus sequence in the regulatory domain of alpha-, beta- and gamma-isozymes of protein kinase C. Treatment of cells for 40 min with a combination of zinc (2-50 microM), zinc ionophore pyrithione and unlabelled phorbol dibutyrate (200 nM) caused up to a ten-fold increase in cytoskeletal protein kinase C and a corresponding decrease in other cellular compartments. Omission of any of the reagents resulted in much less or no translocation. These effects were inhibited by 1,10-phenanthroline, which chelates zinc, and were not seen with calcium. Increase in cytoskeletal protein kinase C persisted for several hours and appeared to involve attachment of the enzyme to actin microfilaments. We propose that zinc, like calcium, regulates the distribution of PKC in cells. However, unlike calcium which controls the binding of PKC to the lipid component on cell membranes, zinc controls the distribution of PKC to membrane cytoskeleton, possibly actin. PMID- 2226844 TI - ATP binding site of mitochondrial creatine kinase. Affinity labelling of Asp-335 with C1RATP. AB - The ATP binding site of mitochondrial creatine kinase from chicken heart has been studied by modifying the purified enzyme with a 14C-labelled ATP analogue, C1RATP, in which the reactive label was covalently bound to the gamma-phosphate group of ATP. The modified enzyme was digested by pepsin, and a single radioactive nonapeptide was isolated by HPLC. Amino acid analysis and direct sequence determination revealed that the isolated peptide corresponds to amino acids 335-343 within the C-terminal region of Mi-CK, this peptide being highly preserved throughout evolution. Asp-335 is very likely the site of modification by C1RATP. The specificity of the ATP analogue for the active site of creatine kinase was demonstrated by the inhibition of the enzymatic activity of Mi-CK by C1RATP and by the prevention of this inhibition bij ADP. PMID- 2226845 TI - Depurination of plant ribosomes by pokeweed antiviral protein. AB - Mammalian ribosomes have been shown to be enzymatically modified by ribosomal inactivating protein (RIPs) via specific depurination of rRNA. Here we report that ribosomes isolated from wheat germ contain intact and undepurinated rRNA and are depurinated by pokeweed antiviral protein (PAP). Pokeweed ribosomes isolated under the same conditions are depurinated. Total RNA isolated from pokeweed in the presence of strong denaturants was found to pbe partially depurinated. We conclude that wheat germ ribosomes are resistant to the endogenous RIP, tritin, but are sensitive to PAP and that pokeweed ribosomes can be depurinated by the N glycosidase activity of endogenous PAP during isolation. PMID- 2226846 TI - A one-variable topographical descriptor for the beta-turns of peptides and proteins. AB - The beta-turn is a common secondary structure in biologically active peptides and globular proteins, where it is widely thought to serve as a molecular recognition site for many biological processes. Although the primary beta-turn recognition requirements are thought to be straightforward, relating mainly to the relative positions of the peptide sidechains, current classifications of beta-turns are complex and are based solely upon the very variable geometry of the peptide backbone. We demonstrate here that beta-turns can be described in terms of a single dihedral angle, which we have called beta, which provides a complete description of the spatial relationship between the entry and exit peptide bonds as well as the relative orientations of the intervening sidechains for any beta turn. This description should prove particularly useful in the development and application of novel peptide mimetic drugs, compounds for which a classification based on a peptide backbone geometry may be entirely irrelevant. PMID- 2226847 TI - Isolation of allophycocyanin B from Rhodella violacea results in a model of the core from hemidiscoidal phycobilisomes of rhodophyceae. AB - Two 'trimeric' allophycocyanin complexes could be isolated from the hemidiscoidal phycobilisomes of Rhodella violacea. AP = (alpha *AP alpha 2AP beta 2AP beta *AP) and APB = (alpha *AP alpha AP alpha APB beta 2AP beta *AP). Lc13.5APB. The isolation was performed by combined methods of gradient centrifugation, hydroxylapatite chromatography and 'native' polyacrylamide gel electrophoresis. AP showed the well-known spectral characteristics of allophycocyanin without linker polypeptide. APB is characterized by its long wavelength absorbing shoulder (675 nm) and fluorescence emission (682 nm), respectively. The existence of two low molecular linker polypeptides Lc12.5 and Lc13.5APB in the phycobilisomes of Rhodella violacea, their stoichiometric calculations and the localization of Lc13.5APB in allophycocyanin B facilitated the construction of a model of the phycobilisome core. PMID- 2226848 TI - A new protein inhibitor of trypsin and activated Hageman factor from pumpkin (Cucurbita maxima) seeds. AB - A protein inhibitor (CMTI-V; Mr 7106) of trypsin and activated Hageman factor (Factor XIIa), a serine protease involved in blood coagulation, has been isolated for the first time from pumpkin (Cucurbita maxima) seeds by means of trypsin affinity chromatography and reverse phase high performance liquid chromatography (HPLC). The dissociation constants of the inhibitor complexes with trypsin and Factor XIIa have been determined to be 1.6 x 10(-8) and 4.1 x 10(-8) M, respectively. The primary structure of CMTI-V is reported. The protein has 68 amino acid residues and one disulfide bridge and shows a high level of sequence homology to the Potato I inhibitor family. Furthermore, its amino terminus consists of an N-acetylates Ser. The reactive site has been established to be the peptide bond between Lys44-Asp45. The modified inhibitor which has the reactive site peptide bond hydrolyzed inhibits trypsin but not the Hageman factor. PMID- 2226849 TI - The primary structure of a triple-helical domain of collagen type VIII from bovine Descemet's membrane. AB - We have isolated and sequenced a fragment of 469 amino acid residues from bovine type VIII collagen. The sequence was composed of a series of Gly-X-Y repeats which was interrupted 8 times by short imperfections. The number and relative location of these interruptions were similar to those of chicken alpha 1(X) and rabbit alpha 1(VIII) chain triple-helical domains. Comparison to published N terminal sequences to two triple-helical fragments of bovine type VIII collagen and to the cDNA derived sequence of the rabbit alpha 1(VIII) chain showed that this fragment was the triple-helical domain of a second type VIII collagen chain which we designate alpha 2(VIII). PMID- 2226850 TI - Codon reading properties of an unmodified transfer RNA. AB - We have previously shown that the Mycoplasma mycoides glycine tRNA (anticodon UCC) effectively reads the codons GGU and GGC in violation of the classic codon reading rules. We have attempted to elucidate what structural elements in this tRNA molecule confer this translational property and in the course of this investigation T7 RNA polymerase transcription of the corresponding gene was used to produce a tRNA devoid of modified nucleosides. Using an in vitro translation system the ability of this tRNA to read the 4 glycine codons (GGU, GGC, and GGG) was tested and it was shown to be as efficient as its normal, fully modified counterpart in the reading of all four codons. This result demonstrates that a tRNA devoid of modified nucleosides is able to efficiently sustain protein synthesis in vitro and, furthermore, that the normal modification pattern of the Mycoplasma glycine tRNA is not essential for the ability of this tRNA to read the glycine codons GGU and GGC effectively. PMID- 2226851 TI - Glucose-stimulated efflux of indo-1 from pancreatic beta-cells is reduced by probenecid. AB - Indo-1 loaded pancreatic beta-cells, isolated from obese hyperglycaemic mice, were studied with respect to cytoplasmic free Ca2+ concentration ([Ca2+]i), efflux of indicator and insulin release. In the absence of glucose there was a continuous efflux of indo-1 which increased upon stimulation with 20 mM of the sugar. The anion exchange inhibitor probenecid reduced both basal efflux of indo 1 and prevented that promoted by glucose. Measurements of [Ca2+]i and insulin release revealed similar results as previously reported with quin-2 and fura-2. Furthermore, probenecid did not influence the [Ca2+]i responses. It is thus possible to reduce efflux of indo-1 probenecid and thereby improve the measurements of [Ca2+]i in pancreatic beta-cells. PMID- 2226852 TI - Heme-CO as a probe of the conformational state of calmodulin. AB - The interaction of heme-CO with calmodulin, in the presence of calcium, leads to a complex of four heme-CO molecules per protein. No interaction was observed in the absence of calcium. The binding of heme-CO to calmodulin was monitored by the shift in the Soret absorption band from 407 to 420 nm (bound form); the four sites are not spectrally identical. The ligand CO can be photodissociated from the calmodulin-heme-CO complex and the biomolecular recombination kinetics also indicate a heterogeneous mixture. The complex does not bind oxygen reversibly. As calmodulin has only one histidine, the hemes are apparently not bound by the iron atom as in hemoglobin, but are probably loosely associated (Kd = 0.5 microM) in hydrophobic pockets which apparently open when the protein is activated by calcium. PMID- 2226853 TI - A genomic clone encoding a cryptophyte phycoerythrin alpha-subunit. Evidence for three alpha-subunits and an N-terminal membrane transit sequence. AB - A genomic library of Chroomonas (Cryptophyceae) DNA has been constructed in lambda EMBL4. Using a synthetic oligomer as a hybridization probe, a clone containing a phycoerythrin alpha-subunit has been obtained and sequenced. The principal alpha 1- and alpha 2-subunits of the holoprotein have been partially sequenced by sequential Edman degradation and differ from the DNA derived sequence, providing evidence for at least 3 alpha-subunit genes. The nucleotide sequence of the alpha-subunit gene is GC rich and encodes an N-terminal extension which is putatively thylakoid-lumen directing. PMID- 2226855 TI - Influence of the aminoacyl-tRNA synthetase inhibitors and the diadenosine-5' tetraphosphate phosphonate analogues on the catalysis of diadenosyl oligophosphates formation. AB - Well-known aminoacyl-tRNA synthetase (ARSase) inhibitors, namely the analogues of amino acids and aminoacyl adenylates (aminoalkyl- and aminophosphonyl adenylates with Ki congruent to 0.1 microM) as well as the diadenosine 5',5'''-p1,p4 tetraphosphate (Ap4A) phosphonoanalogues, were for the first time used for the Ap4A biosynthesis regulation. Effects of a set of such compounds on lysyl-, phenylalanyl- and alanyl-tRNA synthetases from E. coli, capable of synthesizing Ap4A in the presence of Zn2+ ions and pyrophosphatase, have been studied. The adenylate analogues were found to inhibit the Ap4A and Ap3A formation (I50 congruent to 6 mM). Aminophosphonic and aminophosphonous acids are not involved in Ap3A and Ap4A biosynthesis and inhibited it at high concentrations. The Ap4A phosphoanalogues slightly inhibited the major reactions of ARSases, as well as the biosynthesis of Ap3A and Ap4A, at a concentration of 5 mM. PMID- 2226854 TI - Gene structure of mouse cathepsin B. AB - The structure of a genomic DNA fragment encoding mouse cathepsin B was characterized. The genomic insert spans 15 kbp and contains 9 exons encoding the 339 amino acid residues of mouse preprocathepsin B. Intron break-points are not found at the junctions of the pre-peptide, pro-peptide and mature enzyme. Like other cysteine proteinase genes, the region around the cysteinyl active site is split by an intron, but in contrast with cathepsins L and H the intron break point is located immediately after the active site. PMID- 2226856 TI - A comparative study of ribosomal and DNA binding protein II from two thermophilic bacteria, Bacillus caldolyticus strain EP 00275 and Bacillus stearothermophilus. AB - Ribosomal and DNA binding proteins (DNA bp II) from an extreme thermophilic bacterium, B. caldolyticus strain EP 00275, were investigated for stability and crystallization and compared to the homologous proteins from B. stearothermophilus. Two-dimensional gel electrophoresis of both types of proteins, the amino acid composition and the sequences of some of the peptides of DNA bp II revealed a close relationship between each other. The physico-chemical characteristics of DNA bp II were similar but different from homologous proteins from T. thermophilus and C. pasteurineum. From our results we conclude: B. stearothermophilus and B. caldolyticus strain EP 00275 are similar organisms with regard to their ribosomal and DNA binding proteins. PMID- 2226857 TI - Enhanced expression of group II phospholipase A2 gene in the tissues of endotoxin shock rats and its suppression by glucocorticoid. AB - We studied the regulation of group II phospholipase A2 (PLA2-II) gene in vivo, using endotoxin shock rat as a model for systemic inflammation. Administration of endotoxin into rats increased PLA2 activity in the plasma, as described by Vadas and Hay, using endotoxin-challenged rabbit. Specific absorption of this activity by anti-PLA2-II antibody indicated that the released PLA2 was PLA2-II. The levels of PLA2-II mRNA were elevated in the aorta, spleen, lung, and thymus but not in the liver and kidney. The tissues with high PLA2-II mRNA contents released a greater amount of PLA2-II than the tissues of control rats. These results suggest that in endotoxin shock rats, PLA2-II is synthesized de novo in the above tissues and released into circulation. Furthermore, our present study demonstrates that glucocorticoid suppresses the enhanced expression of the PLA2-II gene in the tissues of endotoxin shock rats. PMID- 2226858 TI - GTP gamma S inhibits early c-myc protein accumulation but not DNA synthesis in Swiss 3T3 fibroblasts. AB - Quiescent Swiss 3T3 fibroblasts stimulated with epidermal growth factor and insulin showed large transient increases in c-myc mRNA and c-myc protein accumulation which were maximal at about 2 h after addition of the co-mitogens. When the cells were loaded with 0.1 mM of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) by transient permeabilisation immediately before mitogenic stimulation, the increase in c-myc mRNA was similar to that observed in unloaded cells but the corresponding c-myc protein peak was reduced by at least 95%. The GTP gamma S completely blocked incorporation of [35S]methionine into cell proteins for 3-4 h after addition of the mitogens, but not thereafter, and caused a delay in the subsequent onset of DNA synthesis by the same period. The data show that less than 5% of the early increase in c-myc protein normally observed after mitogenic stimulation is required for its obligatory role in the progression of cells to S phase implied by other evidence. PMID- 2226859 TI - D1-D2 complex of the photosystem II reaction center from spinach. Isolation and partial characterization. AB - A pigment-protein complex consisting of D1 and D2 proteins, but depleted in the two lower molecular mass components of photosystem II, i.e. cytochrome b-559 and psbI gene product, has been isolated by octyl-beta-D-glucopyranoside treatment of the purified photosystem II reaction center complex from spinach [(1987) Proc. Natl. Acad. Sci. USA 84, 109-112], followed by separation by high performance liquid chromatography using a gel-permeation column (TSK G3000 SW). The isolated complex is photochemically active in the photoreduction of intrinsic pheophytin a under steady-state illumination, in the presence of dithionite and methyl viologen, and exhibits pigment stoichiometries similar to those in the untreated reaction center, indicating that the D1-D2 complex provides the site of primary photochemistry in photosystem II, as well as the principal binding sites of pigments in the reaction center. PMID- 2226860 TI - Purification and characterization of mouse DNA polymerase alpha devoid of primase activity. AB - A simple method was developed for the isolation of primase-free DNA polymerase alpha from the DNA polymerase-alpha-primase complex of mouse FM3A cells. The polymerase was separated from primase subunits by chromatography on a single stranded DNA-cellulose column in the presence of 50% etylene glycol. The primase free DNA polymerase-alpha contained two polypeptides with molecular masses of 180,000 and 68,000. Analysis of the DNA products with poly(dA)-oligo(dT)10 as template-primer revealed that both primase-free DNA polymerase-alpha and the DNA polymerase-alpha-primase complex predominantly synthesized short DNA with less than 30 nucleotides, but that the DNA polymerase-alpha-primase complex also synthesized some longer DNA with more than 300-400 nucleotides. PMID- 2226861 TI - Identification of phosphopeptides by mass spectrometry. AB - Phosphopeptides can be identified by ion spray mass spectrometry. The method was tested with phosphokemptide and with a proteolytic digest of one subunit (delta subunit) of the nicotinic acetylcholine receptor. In the latter one peptide containing tyrosine phosphate, one with two serine phosphates, and two different peptides each containing one serine phosphate were unambiguously identified. Thus it is proven that ion spray mass spectrometry can be applied for the localization of phosphorylation sites in a known primary structure. PMID- 2226862 TI - The domain organization of the plant thylakoid membrane. AB - A model of the photosynthetic membrane from higher plants is presented. The different photosystems, PSI alpha, PSI beta, PSII alpha and PSII beta, are located in separate domains. The photosystems with the largest antenna systems, the alpha systems, are in the grana and the other in the stroma lamellae. In each grana disc PSI alpha is located in a flat annulus surrounding a circular PSII alpha domain. In this the PSII alpha units with the largest antennae are found in the center. The model is consistent with results from recent membrane fractionation experiments. PMID- 2226863 TI - A common motif of two adjacent phosphoserines in bovine, rabbit and human cardiac troponin I. AB - From rabbit and human cardiac troponin I N-terminal mono and bisphosphorylated peptides were isolated which were obtained from Lys-C proteinase digests. Two adjacent phosphoserine residues could be localized in each phosphopeptide following further tryptic digestion. The previously published sequence of rabbit cardiac troponin I had to be corrected. Two adjacent phosphoserine residues are a common motif in the very similar sequences of bovine, rabbit and human cardiac troponin I. The N-terminal sequences are: AcADRSGGSTAG DTVPAPPPVR RRS(P)S(P)ANYRAY ATEPHAK (bovine), AcADESTDA-AG EARPAPAPVR RRS(P)S(P)ANYRAY ATEPHAK (rabbit), (Ac,A,D/N,G,S,S,D/N,A,A,R) EPRPAPAPIR RRS(P)S(P)-NYRAY ATEPHAK (human). PMID- 2226864 TI - Time-resolved fluorescence studies on mutants of the dihydrolipoyl transacetylase (E2) component of the pyruvate dehydrogenase complex from Azotobacter vinelandii. AB - Fluorescence anisotropy decays were measured for the wild-type dihydrolipoyl transacetylase (E2) component of pyruvate dehydrogenase complex from Azotobacter vinelandii and E. coli and for E2-mutants from A. vinelandii in which the alanine proline-rich sequence between the binding domain and the catalytic domain is partially or completely deleted. In both E2-mutants the rotational mobility of the lipoyl domain and the overall activity after reconstitution of the complex are significantly decreased indicating the important role of the deleted sequence for the movement of the lipoyl domain and the transfer of substrates between the different active sites within the complex. PMID- 2226865 TI - The primary structure of DNA binding protein II from the extreme thermophilic bacterium Thermus thermophilus. AB - The primary structure of DNA binding protein II (DNA bp II) from the extreme thermophilic bacterium Thermus thermophilus has been established by combination of manual and automated techniques. The protein has 95 residues and a molecular mass of 11,843. Comparison of the primary structure with the known sequence data of DNA bp II from Clostridium pasteurineum, Baccillus stearothermophilus, Escherichia coli, Rhizobium meliloti, Anabena, Thermoplasma acidophilum, Pseudomonas aeruginosa and Bacillus caldolyticus reveals a clear homology among these small basic proteins. In particular, two short sequences in the middle and C-terminal part of the proteins (residues N-Gly-Phe-Gly-X-Phe and Pro-X-Thr at positions 46-51 and 63-65, respectively) are completely conserved. PMID- 2226866 TI - Transforming growth factor beta and a mesoderm inducing factor from human blood platelets are different proteins. PMID- 2226867 TI - A CD study of interactions of ellipticine derivatives with DNA. Relations with the in vitro cytotoxicity. AB - UV-absorption and circular dichroism (CD) experiments showed that ellipticine derivatives may interact with DNA according to 3 possible binding modes depending on their structure and concentration. The first mode concerned intercalation of 1 methyl-9-hydroxyellipticine (1-Me-HE) with its long axis perpendicular to the long axis of base pairs. The same drug was able to bind to external sites (second mode) once the intercalation sites were saturated at high concentration. The third mode illustrated by 1,2-dimethyl-9-hydroxyisoellipticinium (1-Me-isoNMHE), concerned self-stacked molecules interacting at the surface of DNA. Biological significance of these different binding modes was then discussed in connection with in vitro cytotoxic activity of compounds. PMID- 2226868 TI - Partial hepatectomy and mediators of inflammation decrease the expression of liver alpha 2-HS glycoprotein gene in rats. AB - Liver mRNA levels of two acute phase reactant (APR) proteins, alpha 2-HS glycoprotein (a major negative APR) and alpha 1-acid glycoprotein (a major positive APR) were measured in male rats at different times after the administration of turpentine, of tumor necrosis factor, or following partial hepatectomy. In every case, a marked decrease in mRNA levels of alpha 2-HS glycoprotein was observed which reached a maximum at 24 h. A concomitant increase of alpha 1-acid glycoprotein mRNA levels was observed under the same conditions. These results indicate that the decreased levels of alpha 2-HS glycoprotein induced by the acute-phase response following inflammatory mediators and partial hepatectomy are due to a down-regulation of the gene expression of this protein in rat liver. PMID- 2226869 TI - Biosynthesis of bisbenzylisoquinoline alkaloids in cultured roots of Stephania cepharantha. AB - Cultured roots of Stephania cepharantha, which are rich sources of bisbenzylisoquinoline alkaloids, were fed 14C-labelled tyrosine, tyramine or dopamine. While tyrosine was well incorporated into the bisbenzylisoquinolines, tyramine and dopamine were poorly incorporated. Incorporated tyrosine was shown to be decarboxylated and stored as tyramine in the roots, then gradually converted to the bisbenzylisoquinolines. Tracer experiments using [3-13C]tyrosine demonstrated that tyrosine was specifically incorporated into the corresponding sites of aromoline, which verified that aromoline was composed of four molecules of tyrosine. The ratio of 13C-enrichments of C-4 and C-alpha in (R) and (S) halves of aromoline was the same within experimental limits. This indicated that the two coclaurine units must have one and the same biogenetic origin. PMID- 2226870 TI - Long term culture of rat soleus muscle in vitro. Its effects on glucose utilization and insulin sensitivity. AB - Rat soleus muscle strips cultured for 24 h in medium 199 were well preserved in terms of electron microscopy; ATP and creatine phosphate concentrations; rates of glucose utilization, glycogen and protein synthesis, and effects of insulin thereon. Culture led to modest changes in fluid spaces and intracellular (K+); increased basal glucose utilization up to two-fold; had no effect on the maximum response to insulin; and had no effect on sensitivity to insulin except in the presence of adenosine deaminase. Thus in vitro neither denervation nor absence of insulin had any marked effects in 24 h to decrease responses to insulin. PMID- 2226871 TI - The three carboxy-terminal amino acids of human interleukin-6 are essential for its biological activity. AB - We have constructed on the cDNA level deletion mutants of human interleukin-6 lacking one, two, three or four amino acids from the carboxy-terminus of the molecule. After in vitro transcription and translation the biological activity of these deletion mutants was determined by two independent bioassays. Both, the mouse B9 cell proliferation assay and the fibrinogen induction assay with the human hepatoma cell line HepG2 led to the following result: already the removal of the last amino acid resulted in a five-fold loss of biological activity. An additional slight reduction was seen when two amino acids were removed from the carboxy-terminus. Interleukin-6 lacking three or four C-terminal amino acids were completely inactive. The presented results emphasize the extreme importance of the carboxy-terminus of interleukin-6 for its biological function. PMID- 2226872 TI - Generation of human endothelin by cathepsin E. AB - Highly-purified cathepsin D processed human big endothelin1-38 into endothelin like fragments but did not appear to generate endothelin1-21 under the conditions employed. By contrast, human cathepsin E specifically cleaved human big endothelin into endothelin1-21 and the C-terminal fragment under identical conditions but did not degrade either product further. PMID- 2226873 TI - Duplex scanning: the second sight of the vascular surgeon. PMID- 2226874 TI - Non-surgical treatment of critical limb ischaemia. PMID- 2226876 TI - Intra-operative arteriography in arterial embolectomy. AB - In a retrospective study, 154 embolectomies in 135 patients with acute arterial occlusion were reviewed and the value of intraoperative arteriography studied. Included in the study were 69 embolectomies of the femoro-popliteal artery in 64 patients, and in 40 (58%) intra-operative arteriography was performed. Of these, 20 were done because of difficulty in passing the Fogarty catheter and/or absent backflow and 20 as a routine procedure where there was easy passage of the catheter and good backflow. In 29 embolectomies (42%) intra-operative arteriography was not performed because some surgeons, doubting the benefit of routine arteriography, did not use it. In 23 cases (58%) intra-operative arteriography led to an extension of the operation. Six out of 20 routine arteriograms (30%) showed incomplete clearance of the arterial tree, resulting in further embolectomy. The amputation rate was 17%, however in the group where routine arteriography was performed it was zero and significantly less than in the non-arteriogram group (23%). The use of intra-operative arteriography in arterial embolectomy surgery is recommended. PMID- 2226875 TI - The natural history of small abdominal aortic aneurysms: an ultrasound study. AB - A retrospective study was undertaken to assess whether, using serial ultrasound examinations, the behaviour of small abdominal aortic aneurysms could be predicted. The average increase in size was found to be 0.3 cm/year. The pattern of increase in size was not affected by age, sex or the presence of hypertension. A proposed course of management of patients with small aneurysms is suggested, particularly if they have other significant medical problems. PMID- 2226877 TI - Real-time B-mode ultrasonography in the diagnosis of postoperative deep vein thrombosis in non-symptomatic high-risk patients. The Venous Thrombosis Group. AB - In a prospective study of 61 patients who were undergoing elective total hip replacement, the accuracy of real-time B-mode ultrasonography (B-US) in the diagnosis of postoperative deep vein thrombosis (DVT) was compared with blindly assessed bilateral ascending phlebography. The overall sensitivity and specificity of ultrasound was 71 and 94%, and the positive and negative predictive values were 77 and 92%, respectively. The sensitivity and specificity for diagnosis of proximal DVT was 73 and 96%, respectively. Thrombi smaller than 1 cm were not detected. It is concluded that B-US may be used as a screening test for postoperative DVT after elective hip surgery. PMID- 2226878 TI - Results of surgical treatment for atherosclerotic renovascular occlusive disease. AB - In this study we retrospectively examined the results of surgery for atherosclerotic renal artery lesions and analysed the factors that may affect postoperative blood pressure response, changes in renal function and late mortality. A total of 326 patients were operated on over a 15 year period and were followed up for periods from 4 to 165 months (mean follow-up time: 37.2 months). An extra renal vascular area was also involved in 91.4% of cases and in 187 (57.3%) a significant involvement of both renal arteries was found and simultaneously treated. Combined revascularisation of other arteries was performed in 50.3% of patients. The indications for surgery were the treatment of extreme hypertension in 243 patients (74.5%), the improvement of renal function in 45 with renal insufficiency, and preservation of the kidney in 38 (11.7%). The preferred method of reconstruction was transaortic endarterectomy (236 cases, i.e. 72.4%) and postoperative angiography demonstrated a normal patent renal artery in 319 of 338 studied renal arteries (94.4%). There were no deaths in the early postoperative period after isolated renal artery reconstruction. Of the 164 patients with simultaneous renal and aortic reconstruction however 14 died during the early postoperative phase. The overall early mortality was thus 4.3% (14 out of 326 patients) and correlated significantly with the extent of the atherosclerotic disease, the age of the patients, the operative technique used and the different intra- and postoperative management during the two different periods of our experience (1974-1980 v. 1981-1989).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226879 TI - Long-term results of venous thrombectomy combined with a temporary arterio-venous fistula. AB - Forty-one patients with acute iliofemoral venous thrombosis were randomised to conventional anticoagulation or acute thrombectomy combined with a temporary arterio-venous fistula (AVF) and anti-coagulation. Follow-up after 5 years in 22 medical and 19 surgical patients revealed slightly more asymptomatic patients (37 vs. 18%) and less frequent severe post-thrombotic sequelae (16 vs. 27%) in the surgical group (N.S.). The iliac vein was more frequently (P less than 0.05) normal following thrombectomy (71 vs. 30%) as demonstrated by radionuclide angiography, but occlusion plethysmography showed an outflow capacity (61 vs. 45 ml/min/100 ml) that was not significantly better. There was no obvious difference in muscle pump function (EVrel) and reflux (Q/EVrel) assessed by foot volumetry. Still, the ambulatory venous pressure was significantly (P less than 0.05) lower in the surgical group. There was a tendency towards better results following thrombectomy in patients with fresh thrombosis and a successful initial procedure. Although the numbers of observations in many cases were too small to provide statistical evidence of benefit with venous thrombectomy + AVF, this procedure seems to improve the long-term outcome following acute iliofemoral venous thrombosis. Since the difference in outcome is not very striking, anticoagulation treatment is still an acceptable alternative. PMID- 2226880 TI - Vein marking through ultrasound coupling gel. AB - It is now common practice to mark the course of the long saphenous vein by duplex scanning prior to in situ or reversed vein bypass grafting. This poses the problem of how best to mark its course durably in the presence of the ultrasound coupling gel on the skin. Blind to two observers, 11 commonly available marking pens were applied to the skin through ultrasound coupling gel, the gel was removed and the skin cleaned using a spirit-based antiseptic solution. The observers then rated the pens in order of performance. We recommend "Pilot Super Color Marker", "Artline 70" and "Edding 3020 Surgical Skin Marker" for preoperative vein mapping. These pens allow rapid marking of the saphenous or other veins through ultrasound coupling gel at the time of duplex scanning, and the marks persist after surgical preparation of the skin. PMID- 2226881 TI - The "isolated" popliteal segment: a comparative evaluation of its vascular resistance. AB - During femoro-popliteal and femoro-distal bypass, measurement of vascular resistance (VR) at the site of graft outflow may be used to quantify "run off". Intra-operative measurements were made in 51 lower limbs to compare VR in different categories of outflow; the "isolated" popliteal segment (IPS group, n = 11), the popliteal artery in continuity with patent vessels to the pedal arch (PIC group, n = 26) and the single calf vessel (SCV group, n = 14). VR was measured both before and after intra-arterial papaverine. The values in the 37 popliteal arteries were correlated with two different methods of arteriographic scoring. Vascular resistance in the IPS group (median 1149 mPRU, P = 0.003) but not significantly different from VR in the SCV group (median 1014 mPRU, range 743 1541 mPRU). VR in the SCV group was significantly greater than that in the PIC group (P = 0.006). After papaverine administration, the same relationships were observed between the IPS, PIC and SCV groups. Both before and after papaverine, VR in the popliteal artery correlated significantly with both arteriographic scores. In terms of VR, the isolated popliteal segment provides an outflow comparable to that of a single calf artery but less favourable than a popliteal artery wtih patent run off. PMID- 2226882 TI - Survival in patients with abdominal aortic aneurysms. Comparison between operative and nonoperative management. AB - This study evaluates the risk benefit relationship in the surgical treatment of abdominal aortic aneurysm (AAA). Two hundred and thirteen patients with AAA diagnosed by CT were selectively managed depending upon the size of the aneurysm, and were followed with a mean follow-up time of 5 years and 4 months. Aneurysms greater than 5 cm were generally operated on if no serious contraindication existed. Aneurysms less than 5 cm were followed by repeated examinations and operated on if an increase in size occurred. Some small aneurysms were operated on for other reasons. Elective surgical management of 134 patients resulted in a thirty day mortality of 7.5%. Later, seven additional patients died from causes related to the surgery. Survival of electively operated patients by life table analysis was 68% at 5 years. A significantly higher mortality was noted among those who had evidence of coronary heart disease at the time of operation. Forty two patients with AAA less than 5 cm at the initial examination were not operated on and three ruptured, but all had grown to a size greater than 5 cm at the time of rupture. Patients with AAA less than 5 cm that were not operated on had a slightly but not significantly higher mortality than those who were operated on electively. This difference was mainly attributable to deaths from cardiac causes and not to ruptures. Patients with aneurysms greater than 5 cm who were not operated on had a significantly higher mortality than those that were, only 14% in the former group survived.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2226883 TI - Selective low-dose thrombolysis in patients with an axillary-subclavian vein thrombosis. AB - The treatment of axillary-subclavian vein thrombosis is still controversial. Development of a post-phlebitic syndrome in patients treated conservatively occurs in many patients. Therefore more aggressive treatment is advocated. We report six patients treated with selective low-dose streptokinase infusion with excellent short-term results. Major complications did not occur. Recanalisation was observed in all patients. Long-term results are not yet available. PMID- 2226884 TI - Prospective randomised evaluation of a new cell saving device in elective aortic reconstruction. AB - In order to evaluate the clinical and haematological implications of salvage autotransfusion using the Haemolite device (Haemonetics, Leeds, UK), 67 aortic reconstructions were studied. Bank blood transfused during the operation fell from a median of four units in the control group to zero using the cell saver (P less than 0.0001), and wound drainage decreased from 250 to 200 ml (P = 0.12). Evidence of fibrinolytic and platelet activation was found during salvage, but no bleeding diathesis was encountered. There was no morbidity or mortality related to the technique, and median hospital stay was reduced in autotransfused patients. The Haemolite is a safe effective device for autotransfusion in elective aortic surgery, and can substantially reduce exposure of both patients and staff to the dangers of homologous blood. PMID- 2226885 TI - Markers of disease severity in peripheral atherosclerosis. AB - Many studies have attempted to define haematological markers of disease severity in patients with coronary artery disease but there are few similar analyses in peripheral arterial disease. We have determined haematological correlates of disease severity in 51 patients with angiographically documented occlusive arterial disease. Transfemoral arteriograms performed within the previous 12 months were visually scored for disease severity using a reproducible method. Fasting venous blood samples were withdrawn on two separate occasions from each patient and a complete lipoprotein and haematological profile obtained. These determinations included total cholesterol and triglycerides, lipoproteins with their respective apoproteins, plasma lipid peroxides, fibrinogen, factors VII and VIII and rheological indices (haematocrit, whole blood and plasma viscosity). Mean values for each parameter were correlated with the angiographic score. Of the significant correlations, total cholesterol, triglycerides, low density lipoprotein and apoprotein B were all significantly inversely related to disease severity, in contrast to plasma lipid peroxides which showed a weak positive correlation (r = 0.27, P = 0.06). The best index of disease severity was the lipid peroxide/total lipid ratio (r = 0.41, P less than 0.005). This data strengthens the hypothesis that lipid peroxides are involved in atherogenesis and also suggests that they are the best available plasma marker of disease severity in patients with peripheral arterial disease. PMID- 2226886 TI - The warm knee sign--an evaluation. AB - The presence of an area of warmth at the knee has been described in cases of arterial occlusion at the popliteal fossa. A study was carried out to evaluate the significance of this sign by comparing clinical and thermographic findings with arteriographic results in a group of 30 patients. The clinical and thermographic findings were described with reference to the symptomatic limb. Clinically, 14/30 (47%) and thermographically, 16/30 (53%) had "positive" warm knee signs. The overall agreement between clinical impressions and thermographic findings was 28/30 (93%). The commonest arteriographic finding in patients with a positive warm knee sign was that the occlusion or stenosis ended at the adductor hiatus. Comparing this arteriographic finding with a positive warm knee sign, sensitivity, specificity, positive and negative predictive values of 73%, 75%, 79% and 69% respectively were obtained suggesting that this is a useful sign, is of proven value and deserves its place in the initial screening of patients with peripheral vascular disease. PMID- 2226887 TI - Urethral strictures and aortic surgery. Suprapubic rather than urethral catheters. AB - Urethral strictures associated with the use of a urethral catheter may be more common after cardiac and aortic surgery when compared with other surgical procedures. The reasons for this are obscure. Fifty-two aortic procedures in males from 1980-1983 were reviewed with an incidence of urethral stricture of 21%. Forty anterior resections of the rectum in which a urethral catheter was used were also reviewed with an incidence of urethral stricture of only 5%. Since 1985 supra-pubic catheters have been used now in over 200 aortic procedures with no morbidity and no urethral stricture. Bacteriuria has been significantly reduced by the use of supra-pubic catheters and there would appear to be considerable advantages in the use of this technique. PMID- 2226888 TI - Vascular tumours in occlusive disease of the iliac-femoral vessels. AB - Two cases of intraluminal tumours of the iliac-femoral vessels are presented. One was a benign haemangioendothelioma of the common femoral vein and the other a leiomyosarcoma of the iliac artery. Their clinical features were similar to those of patients having venous thrombosis and atherosclerotic occlusive disease respectively. Consequently every physician specialized in vascular disease should be aware of intraluminal tumours as an uncommon explanation of these common clinical pictures. PMID- 2226889 TI - Episodic intermittent claudication associated with a Baker's cyst. AB - Baker first described synovial cysts in the leg in connection with diseases of the knee joint. Whilst the majority are asymptomatic, some present as a localised swelling behind the knee, and others either compress the popliteal vein or rupture and can be misdiagnosed as deep vein thrombosis; transmitted pulsation through the cyst can suggest the presence of a popliteal aneurysm. This paper documents a case of intermittent claudication of the lower limb secondary to compression of the popliteal artery by a Baker's cyst. PMID- 2226890 TI - Pseudomembranous colitis after abdominal aortic aneurysm repair. AB - We report three patients who developed pseudomembranous colitis following aortic aneurysm resection. Colonic ischaemia can occur after such surgery and ischaemic colonic mucosa is known to be more susceptible to damage by bacteria and their toxins. This colonic ischaemia together with the antibiotic prophylaxis used may render aortic aneurysm patients susceptible to pseudomembranous colitis. It is important to distinguish pseudomembranous from ischaemic colitis in these patients as specific and effective drug therapy can be given to those with the pseudomembranous type. PMID- 2226891 TI - [The anatomicophysiological characteristics of the genitalia of girls]. PMID- 2226892 TI - [The prevention of myopia and its complications]. PMID- 2226893 TI - [Erythremia]. PMID- 2226894 TI - [Chronic bronchitis in the miners of deep coal mines]. PMID- 2226895 TI - [Ultrasound in the treatment of surgical wounds]. PMID- 2226896 TI - [Arthrosis of the I metatarsophalangeal joint]. PMID- 2226898 TI - [The extra sense without mysticism]. PMID- 2226897 TI - [The aspects of contraception (the experience of sociological research)]. PMID- 2226899 TI - [The basic principles of resuscitation in severe combined trauma]. PMID- 2226900 TI - [Physical methods for treating the sequelae of the crush syndrome]. PMID- 2226901 TI - [The history of medical first aid in Petersburg]. PMID- 2226902 TI - [Pregnancy and labor following cesarean section]. PMID- 2226903 TI - [The preclinical diagnosis of late toxicosis at the prehospital stage]. PMID- 2226904 TI - [Stenocardia of effort]. PMID- 2226905 TI - [The polycystic ovary syndrome]. PMID- 2226906 TI - [The work experience of the student study circle at Moscow Medical College No. 17]. PMID- 2226907 TI - [Pregnancy and labor in women with a large fetus]. PMID- 2226909 TI - When is enough enough? PMID- 2226908 TI - Current concepts of beta-endorphin physiology in female reproductive dysfunction. AB - beta-Endorphin has a role in the regulation of the normal menstrual cycle and possibly in the onset of puberty. We have reviewed the evidence pointing to an alteration in this neuropeptide that may contribute to the pathogenesis of various reproductive dysfunctions. Elevated or high levels of beta-endorphin have been associated with exercise-associated amenorrhea, stress-associated amenorrhea, and polycystic ovarian syndrome. Depressed or low levels of beta endorphin have been associated with PMS and menopause. Alterations in the levels of beta-endorphin may change the pulsatile release of GnRH via noradrenergic and/or dopaminergic pathways. We have primarily focused on beta-endorphin as representative of the endogenous opioid peptides, but other opioid peptides may also contribute to the pathogenesis of various types of reproductive dysfunction. Perhaps it will become possible to characterize and hone our understanding of the function of beta-endorphin and the other substances composing the endogenous opioid peptides. A better understanding of their role in physiological as well as pathophysiological processes may allow for the development of rational approaches to the treatment of specific disorders pertaining to reproduction. Many questions remain unanswered. Among the most relevant are: what is the precise mechanism of action by which beta-endorphin exerts its influence on pulsatile GnRH release? Is there a functional relationship between CNS and peripheral (serum) levels of beta endorphin? Are the detected changes in beta-endorphin levels merely associated, or are they a cause of a particular disorder? Since it took almost 40 years between the time prostaglandins were first discovered and eventual realization of their clinical application, it may take some time before the beta-endorphin story is complete. PMID- 2226910 TI - Hormonal treatment of functional ovarian cysts: a randomized, prospective study. AB - Estrogen (E)/progestin therapy for functional ovarian cysts is widely used in clinical practice, but the efficacy of this treatment has not been determined in controlled trials. In this study, we examined the effect of E/progestin administration in a group of infertility patients enrolled in a program of ovulation induction who had cysts identified by transvaginal sonography. Patients were randomized to receive either norethindrone 1 mg/mestranol 0.05 mg/d (group A, n = 24) or no treatment (group B, n = 24) for up to 6 weeks. Patients were re evaluated by sonography at 3, 6, and 9 weeks after entry into the protocol. The ages, mean cyst diameters, and proportions of patients having received gonadotropins in the previous menstrual cycle were not significantly different among the two groups. All patients who had a sonographic abnormality persisting for 9 weeks were surgically explored and found to have pathological cysts. The rate of disappearance of functional ovarian cysts was not affected by E/progestin treatment. PMID- 2226911 TI - Serum lipids and lipoproteins in continuous or cyclic medroxyprogesterone acetate treatment in postmenopausal women treated with conjugated estrogens. AB - This study evaluates effects on serum lipids of continuous or sequential progestogens for hormonal replacement in women. Subjects received either a cyclic regimen of replacement (0.625 mg/d of conjugated equine estrogens (Es) for 25 days/month and 10 mg medroxyprogesterone acetate [MPA] for the last 13 days of E) or 0.625 mg/d E along with either 5 or 10 mg MPA (Provera, Upjohn Company, Kalamazoo, MI). Study parameters were measured over a 24-week period. No differences in total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoproteins I and II, sex hormone-binding globulin, or serum MPA levels were noted between the sequential and 5 mg continuous group. The 10 mg MPA group did not have an increase in HDL or decrease in low-density lipoprotein as did the other groups. PMID- 2226912 TI - Further observations on the doubling time of human chorionic gonadotropin in early asymptomatic pregnancies. AB - The doubling time (DT) of human chorionic gonadotropin (hCG) in serum was investigated retrospectively using serial serum hCG values that had been obtained from asymptomatic pregnant women with a prior history of infertility. The DT of hCG did not increase significantly as pregnancy advanced during the period in gestation when the serum hCG concentration was less than 10,000 mIU/mL (International Reference Preparation). Serum hCG concentrations increased subnormally in 2 of 60 women with normal intrauterine pregnancies, 5 of 8 women with asymptomatic ectopic pregnancies (EPs), and in 2 of 8 asymptomatic women who subsequently aborted their pregnancies. Neither the sensitivity nor the specificity of serial hCG testing for EP was enhanced by adopting different test criteria at different serum hCG concentrations. PMID- 2226913 TI - Oocyte retention after follicle luteinization. AB - Indirect evidence supports the existence of the luteinized unruptured follicle syndrome in infertile women. To seek direct evidence of oocyte retention, infertile and normal women were studied in the early and midluteal phase by visual documentation of ovulation stigma, needle aspiration of ovarian follicles, and peritoneal fluid collection for estradiol and progesterone assay. Luteal phase was confirmed by endometrial biopsy (postovulation day 2 to 8). In normal control subjects (n = 16), 25% of test cycles were stigma-negative and no oocytes were recovered. In infertile group (n = 23), 43% of test cycles were stigma negative. Five oocytes were recovered including one from a stigma-bearing follicle. Peritoneal fluid steroid levels failed to discriminate stigma-positive from stigma-negative cycles in either group. Oocyte retention after luteinization occurs in infertile women. PMID- 2226914 TI - Accelerated dissolution of luteal-endometrial integrity by the administration of antagonists of gonadotropin-releasing hormone and progesterone to late-luteal phase women. AB - Sequential blockade of gonadotropin-releasing hormone (GnRH) and progesterone (P) receptors by potent antagonists (Nal-Glu GnRH antagonist and RU486) was conducted in late-luteal phase women to develop a once-a-month birth control method by timed advancement of ongoing luteolysis and endometriolysis. Hormonal dynamics and timing of uterine bleeding during the antagonists' imposed luteal-follicular transition were compared with spontaneous (1st to 2nd) and recovery (2nd to 3rd) cycles in 10 normally cycling women. Serum luteinizing hormone (LH) and follicle stimulating hormone levels declined (47 +/- 4.3% and 24 +/- 3.0%, respectively) by 24 hours after Nal-Glu injection, which accelerated the ongoing luteolytic process, as evidenced by more rapid declines of serum concentrations of estradiol, P, and ir-inhibin, as compared with the corresponding control cycle. This was accompanied by the prompt (16 +/- 3.2 hours after RU486) onset of a single episode of uterine bleeding, which was advanced by 2 days. Whereas the luteal phase length was foreshortened by 2 days, the subsequent follicular phase duration was prolonged by 2 days with a normal sequence of follicular maturation, LH surge, and luteal function during the recovery cycle. We conclude that the late-luteal sequential administration of antagonists of GnRH and P resulted in acceleration of the ongoing luteolytic and endometriolytic processes without functional alterations of the subsequent cycle. PMID- 2226915 TI - Endocervical chlamydial deoxyribonucleic acid in infertile women. AB - The presence of chlamydial deoxyribonucleic acid (DNA) was evaluated by DNA hybridization in endocervical cells of infertile and normal fertile women. Chlamydial DNA was detected in 49 of 186 (26.3%) infertile patients, which is significantly more common than in fertile control individuals (12.5%, or 8 of 64 individuals). Among infertile patients, 49.3% (33 of 67) of those with tubal factors as cause of infertility and 13.4% (16 of 119) of those with nontubal factors were found to contain chlamydial DNA in their endocervical cells. The results show that chlamydial DNA could be found significantly more frequently in endocervical cells of infertile patients with tubal factor than those without tubal factors or in normal controls. PMID- 2226916 TI - Late onset adrenal hyperplasia: mutation at codon 282 of the functional 21 hydroxylase gene is not ubiquitous. AB - Ten patients affected with 21-hydroxylase (21-OH) deficient late-onset adrenal hyperplasia were studied to determine the prevalence of a mutation at codon 281 of the functional 21-OH gene (CYP21B) that results in a valine to leucine amino acid shift. This mutation has been reported in eight unrelated late-onset adrenal hyperplasia patients of Ashkenazi Jewish descent possessing the human leukocyte antigen-B14,DR1 haplotype. Normally, there are two 21-OH genes; a pseudogene (CYP21A) and a functional gene (CYP21B). The aberrant codon 281 sequence is normally present only in CYP21A. In all of our late-onset adrenal hyperplasia patients, hybridization of an oligonucleotide probe specific for this mutation was demonstrated to CYP21A but not to CYP21B. The mutation at codon 281 of CYP21B does not appear to be a ubiquitous genetic marker for 21-OH deficient late-onset adrenal hyperplasia, suggesting that this disorder may demonstrate the same molecular heterogeneity as congenital adrenal hyperplasia. PMID- 2226917 TI - The interaction of parameters of male and female fertility in couples with previously unexplained infertility. AB - A prospective study was undertaken of the relationship between semen variables, serial endocrine and follicular ultrasound measurements in one complete menstrual cycle, and the treatment-independent chance of conception for couples who were referred with unexplained infertility. For the 91 couples studied, the mean length of infertility was 70 months. A 100% follow-up rate was achieved. When a stepwise analysis was performed examining semen variables and ultrasonographic and endocrine variables, the mean ratio of salivary progesterone/plasma estradiol between days +1 and +3, with respect to the luteinizing hormone surge and the Grade 2 motile sperm density, were the only variables that achieved the 5% level of significance. There was a highly significant relationship between the product of these two variables and the chance of conception. This study clearly demonstrates an interaction between parameters of male and female fertility. PMID- 2226918 TI - Subzonal insemination for the alleviation of infertility. AB - Methods were developed to facilitate the use of subzonal insemination to achieve fertilization in vitro. A clinical trial was undertaken in those patients having previously failed to achieve fertilization by in vitro fertilization, and in those presenting with severe oligospermia/oligoasthenospermia. From 85 patients, 585 oocytes were obtained. Of these, 0.3% had been "activated" parthenogenetically in vivo, 369 (72%) at metaphase II underwent subzonal insemination, 15% were fertilized, and 0.5% had three pronuclei. Thirty-eight percent of the patients had fertilization with 36% having a replacement. One conceptus was replaced in 19 patients, two conceptus in 8 patients, and three in 4 patients. A twin and two singleton pregnancies were established. PMID- 2226919 TI - The role of tubal pathology and other parameters in ectopic pregnancies occurring in in vitro fertilization and embryo transfer. AB - Contradictory findings were reported concerning the role of tubal disease in the genesis of ectopic pregnancy in in vitro fertilization and embryo transfer (IVF ET). We report on six ectopics that occurred in 141 IVF-ET pregnancies (4.3%). All of the six cases were among 84 patients with tubal disease, and none occurred in the remaining 57 patients with other etiological factors. No correlation was found in other parameters including: ovulation induction, number of embryos transferred, and luteal support. A comparison between the ectopics and six matched controls demonstrated similar estradiol levels, but beta-hCG levels on day 15 to 17 after ET were lower. Homolateral salpingectomy was performed in all six cases, but a contralateral resection was carried out in three of them. More comprehensive studies are needed to clarify whether tubal pathology really increases the risk for ectopic gestation in IVF-ET. PMID- 2226920 TI - Binovular human ovarian follicles associated with in vitro fertilization: incidence and outcome. AB - Binovular follicles were found in 15 (0.3%) of 4,695 follicles containing oocytes. These binovular follicles were either with adjacent cumulus complexes (9 cases), or separate corona radiata and common cumulus mass (1 case), or two oocytes within a single zona pellucida (5 cases). In each of the latter form, there was a smaller and a larger oocyte. All the smaller oocytes and two larger ones possessed a germinal vesicle, whereas the remaining three larger oocytes were mature and developed normally. Though being exposed to the same intrafollicular milieu, there can be a difference in the maturity of the nucleus and characteristics of the cytoplasm of both oocytes. PMID- 2226921 TI - Psychological assessment and follow-up after in vitro fertilization: assessing the impact of failure. AB - The present study was conducted to assess the immediate psychological impact of failed in vitro fertilization (IVF). Emotional status and marital functioning were also examined pre-IVF, and both demographic information and psychological test scores were evaluated as predictors of reaction to treatment failure. After a failed first cycle, both males and females showed significant increases in anxiety and depressive symptoms. Although group means were not clinically elevated and most participants were coping adequately, the prevalence of both mild and moderate depression increased substantially, particularly among women. In addition, women without children were a subgroup particularly vulnerable to the stress of failure. Predisposition towards anxiety, pre-IVF depressive symptoms, and fertility history were the most important predictors of emotional response. Treatment implications of these findings were discussed. PMID- 2226922 TI - Effects of incubation time in serum and capacitation on spermatozoal reactivity with antisperm antibodies. AB - Sperm reside within the female reproductive tract before the occurrence of fertilization. During this time they undergo surface modifications associated with changes in their functional state. To study their antigenic expression, capacitated and acrosome-reacted sperm were incubated with sera that had previously been tested for antisperm antibodies against fresh washed sperm, as detected by indirect immunobead binding. Forty-eight percent of previously positive and 20% of previously negative sera reacted differently with sperm after an extended time (18 hours) of incubation in serum or after sperm capacitation. These results suggest that current techniques of antisperm antibodies detection be modified to include testing sera after prolonged incubation times with both capacitated as well as fresh sperm. PMID- 2226924 TI - Protein differences between normal and oligospermic human sperm demonstrated by two-dimensional gel electrophoresis. AB - Protein expression by sperm obtained from men with normal semen analysis and men with oligospermia were evaluated by two-dimensional gel electrophoresis. Proteins were solubilized in a 9.5 M urea/2% Nonidet-P40 (LKB, Bromma, Sweden) lysis buffer and underwent second dimension separation on 10 to 16% polyacrylamide gradient gels. A set of 36 invariant proteins was identified in all normospermic samples, whereas 8 of 10 evaluable oligospermic samples lacked 1 or more of the invariant proteins. Proteins absent in oligospermic samples may be critical to normal sperm function and may serve as markers for infertility. PMID- 2226923 TI - A reverse (antibody capture) enzyme-linked immunosorbent assay for detection of antisperm antibodies in sera and genital tract secretions. AB - A reverse (antibody capture) enzyme-linked immunosorbent assay (ELISA) for detection of antisperm antibodies has been developed. The assay enables detection of immunoglobulin (Ig) M, IgG, IgA, or IgM, IgG, and IgA--antisperm antibodies in serum, cervical mucus, and seminal plasma samples. The reverse ELISA is more specific and sensitive than conventional ELISA in detecting human antisperm antibodies of different isotypes. Using this assay, statistically significant differences in levels of antibodies between infertile and fertile individuals were demonstrated in sera and in genital tract secretions. Studies with 143 infertile couples revealed that the presence of antibodies in sera was not necessarily reflected in individual's genital tract secretion and vice versa. These data emphasize the importance of detecting antisperm antibodies in sera as well as in genital tract secretions for correct evaluation of sperm immunity. PMID- 2226925 TI - Pooled sequential ejaculates: a way to increase the total number of motile sperm from oligozoospermic men. AB - We investigated the yield of total number of motile spermatozoa from oligozoospermic men by pooling two closely spaced sequential ejaculates. Semen characteristics were compared between sequential ejaculates (within a period of 1 to 4 hours) of 18 oligozoospermic males (sperm concentration less than 20 X 10(6)/mL and total sperm count less than 40 X 10(6) in the ejaculate) and a control group of 16 normozoospermic men. Whereas the median total number of motile sperm of normozoospermic males significantly decreased from 70 X 10(6) in the first ejaculate to 23 X 10(6) in the second sequential ejaculate, such a decrease was not detected in oligozoospermic males, 3.6 X 10(6) and 3.1 X 10(6), respectively. The percent of normozoospermic and oligozoospermic men who demonstrated a decreased (less than 50%), a comparable (50% to 150%), or an increased (greater than 150%) total motile sperm count in the second ejaculate in comparison with the first ejaculate were 69%, 31%, and 0 versus 39%, 28%, and 33%, respectively. Consequently, pooling of two sequential ejaculates significantly increased the median total number of motile sperm from normozoospermic males by 144% and from oligozoospermic males by 329%, (to 10.2 X 10(6]. We suggest that pooling of two sequential ejaculates from oligozoospermic males is a simple and cost effective method to increase significantly the total number of motile sperm for intrauterine insemination, in vitro fertilization, gamete intrafallopian transfer, or semen cryopreservation. PMID- 2226926 TI - Studies on requirements for trackpoints in CellSoft automated semen analysis. AB - The CellSoft (CRYO Resources, Ltd., New York, NY) system for computer-assisted sperm analysis was evaluated as to the appropriate settings for trackpoints. Fifty-eight human spermatozoa exhibiting complex swimming modes were chosen for analysis at room temperature. The accumulated measures for curvilinear velocity, linearity, mean and maximum amplitude of lateral head displacement, and beat cross frequency were determined over a range of trackpoints from 2 to 37. Stable measures (within the 95% confidence interval at 37 frames) were observed at 4 frames for curvilinear velocity and at 20 frames for linearity. The corresponding figure for mean amplitude of lateral head displacement and beat cross frequency was 8 frames. We conclude that the frame requirements concerning measures for curvilinear velocity/linearity and mean amplitude of lateral head displacement/beat cross frequency should be 20 and 8, respectively. Thus, 20 consecutive frames to analyze will suffice. PMID- 2226927 TI - Effect of serum from patients with minimal to mild endometriosis on mouse embryo development in vitro. AB - Two-cell mouse embryos were cultured at 37 degrees C in 5% CO2, 95% air with a 7.5% serum supplement from patients with minimal to mild endometriosis, (group I, n = 31), tubal factor (group II, n = 33), male factor (group III, n = 17), fetal cord samples (group IV, n = 37), and Ham's F-10 medium (Gibco, Grand Island, NY) without a serum supplement (group V, n = 30). The progression to blastocyst stage (mean percent +/- SE) at 96 hours in groups I, II, III, IV, and V was 29.9% +/- 3.7%, 60.6% +/- 4.9%, 56.2% +/- 5.2%, 61.7% +/- 5.8%, and 63.2% +/- 6.9%, respectively. Serum factors appear to be associated with an inhibition of early embryogenesis, which may explain the decreased fertility rates observed in patients with minimal to mild endometriosis. PMID- 2226928 TI - The effect of cocaine on oocyte development and the follicular microenvironment in the rabbit. AB - We examined the effects of cocaine exposure in the rabbit on in vitro oocyte development and on steroidal content of follicular fluid (FF) and serum progesterone (P). Cocaine hydrochloride (0, 10, 20, 40, or 80 mg/kg) was administered daily subcutaneously for 5 days to New Zealand White female rabbits before superovulation. On the last day of cocaine administration, animals were given human chorionic gonadotropin intravenously, and laparotomy was performed 6 to 8 hours later. During laparotomy, ovaries were removed, the number of follicles recorded, oocytes retrieved, and FF was obtained. In vitro fertilization (IVF) was then performed on the oocytes and the rate of cleavage observed. For all cocaine dosage groups, no differences were observed in the number of follicles present, number of oocytes retrieved, or IVF and cleavage rates. Cocaine did, however, decrease periovulatory serum P, and FF P, whereas FF estradiol concentrations increased. This suggests that short-term cocaine exposure affects the follicular steroid milieu, possibly by delaying granulosa cell luteinization. PMID- 2226929 TI - Peritoneal fluid fractions from patients with endometriosis do not promote two cell mouse embryo growth. AB - Peritoneal fluid (PF) from 10 infertile patients with endometriosis, obtained during the follicular phase of the cycle during laparoscopy, did not promote two cell mouse embryo growth to the extent observed by fluid obtained from seven normal controls. Five molecular weight (MW) fractions were obtained by ultrafiltration, and each was used as media supplement in the assay and compared with PF fractions from normal controls. All fractions of PF from patients with endometriosis inhibited mouse embryo growth to a greater extent than did normal controls. However, the MW fractions greater than 100,000 daltons showed greater inhibition of embryo development than did fractions less than 100,000 daltons. This study of cell-free PF suggests the presence of a humoral factor greater than 100,000 daltons that is inhibitory on mouse embryo growth. PMID- 2226930 TI - Retroperitoneal mobilization of the vas deferens in the complex vasovasostomy. AB - Anatomic distances along retroperitoneal, inguinal, and infrainguinal segments of the vas deferens were measured in 14 formalin fixed cadavers and in 15 recently postmortem males. There were no significant differences in segment lengths between the two groups nor between the right and left vasa. Data from the recent postmortem group reveals a mean length of 5.83 +/- .65 cm to be gained from retroperitoneal mobilization of the vas deferens. This information is important to surgical decisions in cases of microsurgical repair of obstructive azoospermia resulting from damage to the inguinal segment of the vas deferens. Data on other vasal segment lengths is beneficial for planning repair in other complex cases of obstructive azoospermia as well. PMID- 2226931 TI - Transient hyperprolactinemia is associated with a midcycle luteinizing hormone surge. AB - This study demonstrates that LH surge cycles in IVF patients were associated with significantly higher serum PRL concentrations than cycles in which a spontaneous LH surge did not occur. Our findings support the hypothesis of concomitant LH and PRL release at the time of the midcycle gonadotropin surge, as well as that of estrogen sensitization of pituitary lactotropes, and suggest a possible mechanism for transient midcycle hyperprolactinemia. PMID- 2226932 TI - Effect of sperm preincubation with follicular fluid on the fertilization rate in human in vitro fertilization. AB - The study investigates the effect of sperm preincubation with FF on the fertilization rate in an IVF program. The oocytes inseminated with FF pretreated semen showed a significantly higher rate of fertilization. The percentage of cleavage and polypronuclear occurrence did not differ from the controls. PMID- 2226933 TI - In vitro fertilization and development of one of two human oocytes with fused zonae pellucidae: case report. AB - This report describes a pair of human oocytes of differing maturities but fused at the zona pellucida, believed to have originated from a binovular follicle. After insemination in vitro, one oocyte fertilized and developed into an expanded blastocyst, whereas the other, which contained a germinal vesicle, degenerated. A biopsy was aspirated from the blastocyst, which subsequently re-expanded but did not hatch. PMID- 2226934 TI - The use of electroejaculation and zygote intrafallopian transfer to achieve a pregnancy after a major gunshot wound to the abdomen: a unique application. PMID- 2226935 TI - Deletion of chromosome 4: 46,XY, del(4) (q31.3) after gamete intrafallopian transfer and in vitro fertilization-embryo transfer. AB - It seems that assisted reproduction technology does not increase the rate of chromosome abnormalities, and up to now, a few cases have been reported. The case we describe here is the first one of monosomy 4q31 in a full-term liveborn after a combined GIFT-IVF procedure. Once more, this case raises the question of whether pregnancies resulting from IVF should be monitored for chromosome abnormalities or not. PMID- 2226936 TI - Hazards of electromagnetic fields to human reproduction: what information is in the scientific literature? PMID- 2226937 TI - Recent editorial--a lightning rod for discussion. PMID- 2226938 TI - Variations of the human sex ratio at birth. PMID- 2226939 TI - [The demonstration of potential-dependent potassium channels in the plasma membrane of secretory cells]. AB - Outward current of the salivary gland cells membrane of chironomus larva activated by the displacement of the membrane potential to the region of positive values has been registered by the voltage-clamp method under conditions of intracellular dialysis in the presence of only the potassium transmembrane gradient. Activation threshold of the current is about +10 mV. Subsequent displacement of the membrane potential to the region of positive values causes an increase of the current. Time constant of the current activation is (652 +/- 57) ms. The current decreases with the intracellular potassium concentration, under the influence of tetraethyl-ammonium and 4-aminopyridine. Thus, high threshold potential-dependent potassium channels are presented in the secretory cells membrane. PMID- 2226941 TI - [The basic patterns in the development of lymph circulatory failure in the heart]. AB - 63 adult rabbits were used to stimulate single physical exercise, acute and relapsing coronary insufficiency, alimentary atherosclerosis and to study adaptive and pathologic changes in the lymphatic channel (LC) of the heart. LC of the heart in animals with alimentary atherosclerosis after cholesterol exclusion from their diet was studied to determine reversibility of these changes. LC of the heart was injected by differently coloured masses and was investigated by the stereoangioscopic method on clarified preparations, on semithin sections and by the electron-microscopic method. Changes in different elements of a lymphatic net were of the stereotype character, as a whole. Morphofunctional reactions determining the development of the chronic insufficiency of the lymph flow in the heart form as successively following phases which change both due to exposition of the pathological process-initiated effect and due to certain endogenic factors arising during arrangement of LC of the heart. PMID- 2226940 TI - [The hypothesis of acupuncture points as polymodal receptors of the ecoceptive sensitivity system]. AB - Hypothesis is proposed that the human brain has the sensory system (ecoceptive sensory system) which responds to changes of the Earth electromagnetic fields (EEFs) and meteorologic factors (MFs). Acupuncture points which are activated easily by adequate somatosensory stimuli (mechanical, temperature) and electromagnetic fields (electropuncture, magnetopuncture) can be polymodal receptors of the ecoceptive sensory system. It is supposed that the sensory endings of acupuncture points are excited by sharp changes ef EEFs and MFs. Through the neuronal brain stem structures, especially through hypothalamus, acupuncture points excitation starts the adaptive mechanisms intended to compensate the brain functional systems deviations, provoked by prolonged EEFs and unsettled weather environmental influences. PMID- 2226942 TI - [The nature of the hypermetabolism and tachycardia in cold adaptation and experimental hyperthyroidism]. AB - The cross circulation method has been used to study contribution of humoral and nonhumoral components to the origin of hypermetabolism (increased level of basal metabolism) and tachycardia under adaptation to cold and experimental hyperthyroidism. Consumption of oxygen, heart rate and rectal temperature have been studied in periods prior to and during the cross circulation. It is shown that under experimental hyperthyroidism contribution of humoral and nonhumoral factors to the origin of hypermetabolism equals 22 and 78%, while that to genesis of tachycardia--44 and 56%, respectively. Under cold adaptation an increase of the basal metabolism level depends on humoral agents by 77% and on changes of the stationary character only by 23%. The nature of adaptation tachycardia is mainly, of the humoral origin (65%). PMID- 2226943 TI - [The protective effect of energy substrates, vitamins, coenzymes and their complexes in the action on the body of the factors of an enclosed space]. AB - Experiments on mice were performed to study a protective action of amino acids and other oxidation substrates (L-aspartic acid, pyruvate, succinate, GABA, alpha ketoglutarate), metabolites (pyridoxal-5'-phosphate) as well as vitamin-coenzyme complexes in combination with oxidation substrate while being under closed space conditions. GABA, aspartate, glutamate possessed the highest protective effect as against alpha-ketoglutarate and succinate. PMID- 2226944 TI - [The effect of hypoxia on the glucose-6-phosphate dehydrogenase activity of the erythrocytes in rats]. AB - Biochemical methods have shown, that adaptation of rats to the conditions of the middle mountains (2100 m above sea level) as well as with subsequent affecting acute hypoxia in the hypobaric chamber (7500 m, 2-5 h and 9000 m, 1-3 h) is accompanied by the increase of the activity of glucose-6-phosphate dehydrogenase. Its level also increases in experiment with nitrite methemoglobinemia and phenylhydrazine anemia, as well as with ionol introduction. PMID- 2226945 TI - [The effect of the antigen-induced splenic suppressor factor on the immune response to different antigens]. AB - Quick-frozen spleen of mice immunized with sheep red blood cells was homogenized and centrifuged. Supernatant was used as a source of suppressor factor (SF). It was shown that SF inhibited antibody immune response to thymus-dependent antigens and delayed hypersensitivity reaction. SF did not inhibit antibody formation to thymus-independent antigen. SF activity disappeared after its treatment with anti Ig immunosorbent. PMID- 2226946 TI - [A comparative analysis of the effect of clofelin on gastric secretory function in man and dog]. AB - It is established that clofelin suppresses the human and dog insulin gastric secretion as well as human basal and histamine secretion. Clofelin has no effect on the secretory function of the dog stomach, stimulated by pentagastrin, carbachol histamine. It is supposed that clofelin-induced suppression of the human histamine gastric secretion takes place due to the inhibition of basal secretory component being a part of the common secretory effect on histamine. Clofelin may be promising drug in the treatment of patients with hypertension and duodenum ulcer. PMID- 2226947 TI - [The role of the duodenojejunal junction in regulating the evacuatory function of the duodenum]. AB - Chronic experiment on dogs was performed to study the effect of duodenojejunal junction exclusion from the evacuatory process on dynamics of gastric and duodenal emptying of the carbohydrate and fatty food. It is established that in the case of exclusion of the duodenojejunal junction, the degree of coordination of gastric and duodenal emptying decreases, dynamics of chyme evacuation from the duodenum considerably changes. It is concluded that the duodenum is not a mere transporter of food coming from the stomach, but has its own regulation mechanisms represented by the duodenojejunal junction and the Treitz ligament. PMID- 2226948 TI - [The effect of ethonium on the fatty acid composition of the lipids in the hepatic and muscular tissues of hypotrophic piglets]. AB - Relative content of unsaturated, in particular polyene fatty acids, being a part of total lipids and lipase activity in the liver tissue and muscular tissue in the hypotrophic pigs is much lower than those parameters in normotrophic ones. Ethonium induces an increase in the percentage of irreplaceable polyene acids in total lipids, activity of lipase and CME in tissues as well as average diurnal increments and preservation percent of youngs. PMID- 2226949 TI - [The protective action of the organic substances in naftusia water on erosive ulcerative lesions of the gastric mucosa in rats undergoing immobilization-cold stress]. AB - It is shown that 7-11-day long consumption (by rats) of water naftusia or organic matters isolated from it which contain carbonic acids and catecholamines possessing paramagnetic activity exerts a preventive effect on stress injuries of the mucous membrane of the stomach. Gastric protective action of naftusia goes with hyperplasia and hypertrophy of argyrophil endocrinocytes and antral mucosa, with an increase of gastrin content in it as well as in blood serum, shortening of the nembutal sleep duration. PMID- 2226950 TI - [The cytological and hormonal characteristics of cell cultures from the testes of newborn piglets]. AB - A cell culture of neonatal pig testes has been studied. Leydig cells, Sertoli cells, sex cells and fibroblasts have been identified by cytologic and cytochemical research methods, Gonadotropin concentration (0.1 U/ml) of nutritional medium, increases proliferation of the Leydig cells and increases their 3-beta-ol-steroiddehydrogenase activity as well as increases amount of lipid inclusions and stimulates testosterone production. The cell culture can be used to treat some forms of hypogonadism. PMID- 2226952 TI - [The dependence of the achievement of students on the individual typological properties of their nervous systems]. AB - A reliable correlation (r = 0.47) between cognitive ability and educational achievement has been determined in 195 students (men and women) aged 21-25. Progress in studies depends also on such individual-typological properties as "strength" of the excitation process (r = 0.46), work reliability (r = 0.49) and functional "mobility" of the nervous brain process (r = 0.38). On the whole, teaching efficiency is determined by a complex of psychophysiological state indices rather than by one of these indices. PMID- 2226951 TI - [The pathomorphological characteristics of the action on the body of the antitumor antibiotic asterin under stress conditions]. AB - The action (on the organism) of antitumour antibiotic asterine isolated from plant of family Asteraceae under stress conditions at D. K. Zabolotnyi Institute of Microbiology and Virology has been pathomorphologically characterized. Asterine is stated to be able to decrease the harmful effect of stressor, preventing the expression of structural alterations in adrenal glands, cortex and lungs of stress-subjected organism. Adaptogenic effect of antitumour antibiotic is confirmed. PMID- 2226953 TI - [The action of reserpine on cholinergic processes in the heart]. AB - Experiments on white rats show that reserpine creates conditions for acetylcholine accumulation in the heart. In early periods after reserpine administration (within 8 hours) this process depends on restriction of mediator hydrolysis. In more distant periods (within 24 hours) synthesis activation adds to the mentioned mechanism. PMID- 2226954 TI - [The dynamics of the autoimmune process in guinea pigs during their acquisition of an experimental neurosis]. AB - Pathogenetic role of the neuroautoimmune reactions in dynamics of the experimental neurosis development has been investigated. Application of the dynamic approach in estimation of the pathological process has permitted analyzing changes in the immunological indices in dynamics of the experimental neurosis development. The results obtained testify to that maximum content of autoantibodies to the nervous tissue, circulating immune complexes and changes in the reaction of neutrophilic injury are observed in the beginning of the experimental neurosis development. PMID- 2226955 TI - [History of the Dental (Stomatologic) Clinic through 1920 (Jozsef Arkovy)]. AB - The Dental Clinic of the Budapest University was established 100 years ago. The prehistory and the history of the first three decades of the clinic is closely attached to the course of life of Professor Jozsef Arkovy (1952 to 1922). Arkovy acquired a medical and dental master certificate in 1876. Between 1881 and 1890 he directs a private dental clinic. This became the basis of the University Dental Clinic opened in 1890 which disposed of a treating hall with 10 dental chairs, a narcosis chamber and a class room. In 1908, the clinic moves into a new building planned for such purpose and its name becomes Clinic of Stomatology. In the new clinic the departments of surgery, conserving dentistry and prosthetic dentistry became separated and there was a bedpatient department as well. Arkovy retired in 1920. PMID- 2226956 TI - [History of the Stomatologic Clinic between 1920 and 1959]. AB - Since 1919 the clinic was directed and developed by Professor Jozsef Szabo (1874 to 1937). His book entitled The Practical Dentistry appeared also in Italian and Spanish. His collaborator was Professor Henrik Salamon (1865 to 1944) distinguished prosthetic, orthodontist and dental historian. The professorate was taken over in spring of 1944 by Professor Karoly Balogh (1895 to 1973) who organized the independent training of dentists. The Clinic of Stomatology became the basis of the Faculty of Dental Science of the Budapest Medical University and of the four dental clinics operating since 1959. Today the building of the Clinic of Stomatology serves for the operating of the Oral Surgery and Dental Clinic. PMID- 2226957 TI - [The significance of the styloid process syndrome in the differential diagnosis of temporomandibular dysfunction]. AB - Two cases are reported on, both patients came to the clinic on the suspicion of temporo mandibular joint disfunction. Their complaints was caused by overdeveloped processus styloideus. After surgical removal of the processus styloideus the complaints ceased. In cases of seemingly temporo mandibular joint disfunction not improving on conventional treatment the possibility of the processus styloideus syndroma has to be considered. PMID- 2226958 TI - [Dental education in the past century, its current status and future trends]. AB - Since the second half of the nineteenth century, two ways of dentist-formation co existed: medically based-, and independent dental education. Medically based dental education,--present until the last decade in four countries of Europe-, favoured the development of oral medicine and surgery. Independent dental education,--specially in Western Europe and USA--realized through prevention a decline in caries and associated dental diseases. According to these changes, treatment needs in future will require low-, and high technology skills, an integration of the dentist into the Primary Health Care Team, as an "Oral Physician". In education a closer relationship between medical and dental subjects, as well as between basic and dental clinical subjects will be necessary. On the basis of E.E.C. decision an agreement on dental curricula in Europe should be attained in the near future. PMID- 2226959 TI - [Xerostomia as a side effect of drugs]. AB - After a definition of xerostomia and a description of it's diagnostics and consequences the most important etiological factors are reviewed with special emphasis on drugs inducing xerostomia as an adverse effect. The most important drugs concerned are summarized in a table indicating generic names as well as proprietary names of preparations marketed in Hungary. Possible therapeutic approaches are also described. PMID- 2226960 TI - [Effect of partial dentures on the residual dentition and the periodontium]. AB - The data of 969 dental arches replaced by partial denture, and 1282 dental arches of the same edentulousness but unreplaced, examined in an unselected population, have been analyzed from the point of view of the occurrence frequency of the gingivitis, the pocket, the movability and the caries. It has been stated that the effect of the prosthesis of the remaining teeth may be evaluated only by comparison with a suitable control group with no dentures. Furthermore, it has been stated that the remaining teeth are not damaged by well planned partial dentures (with metal base plates) while the wrongly planned dentures (with plastic base plates) develop a significant damaging effect. PMID- 2226961 TI - [Stomatologic developmental abnormalities causing speech defects, their incidence in hereditary syndromes]. AB - Inherited disturbances of development of the mouth and the surrounding oral environment: lips, tongue, teeth palate as well as lesion of the central motoric kernels of certain brain nerves may cause grave speech defects. In the report a number of hereditary syndromes are listed among the symptoms of which the speech defect has dominant significance. Short description is given of dental methods by means of which the defects can be eliminated or, at least, are curable. PMID- 2226962 TI - [Malocclusion of the front teeth in wearers of complete upper and lower dentures]. PMID- 2226964 TI - [Experience with amalgams manufactured by Southern Dental Industries (Australia)]. AB - The gamma 2 phaseless amalgam of the firm Southern Dental Industries (SDI) was tested. None of the 205 fillings showed level deviations, unevenness, secondary caries and breakage. A minimum size gap was found in 2 cases. PMID- 2226963 TI - [Development and therapeutic possibilities in pathological bone changes in the alveolar ridge]. AB - For preventing pathological leison its healing as well as slowing down of the progress of the already formed course the employment of prosthetic therapy is suggested. Various solutions are presented which, on basis of their clinical experiences, are deemed successful therapeutics. Finally, in case of the above mentioned statuses attention is called to the possibilities of error in the course of individual stages of work in making denture as well as to the possibility to their elimination. PMID- 2226965 TI - [ Aligning of retained and impacted teeth using and orthodontic device]. PMID- 2226966 TI - [Use of a finger sucking prevention device (report of a case)]. PMID- 2226967 TI - Patient outcomes: the time is right. PMID- 2226968 TI - Heparin therapy. PMID- 2226969 TI - Preventing increased ICP. PMID- 2226970 TI - From Florence Nightingale to critical care nursing: a visit to Istanbul. PMID- 2226971 TI - Air emboli: a potentially lethal complication of central venous lines. PMID- 2226972 TI - A regional approach to entry-level critical care education. AB - The education and training of the novice critical care nurse place a constant financial demand on many Puget Sound area hospitals. Critical care educators from this area, committed to cost-effective, high-quality education, enhanced through precepted clinical experience, assessed the need for a collaborative approach among institutions. Jointly we have successfully planned, implemented, and evaluated a cooperative educational program. To date, the program has served to reduce the costs of preparing the RN entering critical care in the Puget Sound area. Application of principles of adult education, timely application of theory to practice, and expansion of the professional role of critical care clinical nurse specialists and educators have also been recognized as outcomes of the CCEC. PMID- 2226973 TI - Esophageal perforation. A case study. PMID- 2226974 TI - A clinical practice journal club: bridging the gap between research and practice. AB - The value of applying the findings of research to nursing practice is obvious. A clinical practice journal club may assist in this process. Monthly in our clinical settings. Our journal club helped to bridge the gap between research and our professional practice. PMID- 2226975 TI - Understanding cardiovascular drug interactions. PMID- 2226976 TI - Trust: a critical element in critical care nursing. AB - All nurses, regardless of specialty, should strive to develop a trusting relationship with their patients. This relationship paves the way for obtaining the accurate and pertinent information necessary to form correct nursing diagnoses. In a critical care unit, this accuracy and trust is essential caused by the intensity of the environment. Support systems are weakened with family members being separated and allowed to visit for only short periods of time. Family members may see a loved one as never seen before, appearing absolutely helpless. A trusting relationship with the critical care nurse could help reinforce and strengthen the weakened support system. Professional nurses spend the greatest amount of time with consumers of health care. This situation places them in a position to influence life-styles. Seeking further assistance or following advice may depend on the quality of the nurse-patient relationship. Specifically for critical care and long-term situations, trusting relationships may make a long, intensive illness less traumatic. Trust built in the critical care area may provide the basis for positive nurse-patient relationships developing throughout the hospitalization and during future interactions with professional nurses. PMID- 2226977 TI - HIV therapy update. PMID- 2226978 TI - Thyroid eye disease. PMID- 2226979 TI - Epikeratophakia for keratoconus. AB - Results of the author's first 15 cases of epikeratophakia for keratoconus are presented. All patients were intolerant of contact lens correction and could not achieve satisfactory acuity with spectacle correction due to corneal ectasia and irregular astigmatism. The average follow-up was 13 months. Seventy-three per cent of eyes treated had a pre-operative spectacle acuity of 6/60 or worse. One eye had a preexisting amblyopia that limited final acuity, but every other eye achieved a post-operative spectacle acuity of 6/12 or better and 50% achieved 6/6. One eye had 11 dioptres of post-operative astigmatism and required penetrating keratoplasty; the remaining eyes had an average astigmatism of 1.9 dioptres. Epikeratophakia appears to be a safe alternative to penetrating keratoplasty in selected cases. PMID- 2226980 TI - Management of diplopia on down-gaze following orbital trauma. AB - Diplopia in the inferior field due to orbital trauma is a notoriously difficult and disabling problem. Even if a blow-out fracture is repaired by current methods, patients may still have diplopia. There also exists another group in whom no demonstrable radiological fracture can be found, and yet there is a severe down gaze deficit. The possible mechanisms of this phenomenon are discussed and the results of horizontal muscle transposition surgery in a series of nine patients is reported. The authors conclude that this procedure is a valuable method of increasing the useful field of binocular single version in these patients. PMID- 2226981 TI - Botulinum toxin therapy in dysthyroid strabismus. AB - We report our experience with the use of Botulinum toxin injection in 38 patients (64 injections) with severe dysthyroid strabismus. Three quarters of the injections led to a decrease in the angle of the squint by a mean 75% of the initial deviation. The average duration of effect was two months. Twenty six patients went on to surgery after stabilisation of their squint and endocrine status. Six patients achieved a stable long-term result with Botulinum toxin only. We suggest these results of treatment of early dysthyroid myopathy are more consistent with the characteristics of inflammatory spasm than contracture. The value of Botulinum toxin as a temporary means of maintaining binocularity in these young patients is discussed. PMID- 2226982 TI - Cataract surgery with intraocular lens implantation in Fuchs' heterochromic cyclitis. AB - The results of cataract extraction with posterior chamber lens implantation in twenty eyes with Fuchs' Heterochromic Cyclitis are reported. No serious operative complications were experienced. The visual outcome has been excellent in all but those eyes with coexistent glaucoma. The postoperative complications seem no more frequent than would be expected for the underlying condition. PMID- 2226983 TI - Secondary intraocular lens implantation: eight year experience. AB - OBJECTIVE: To investigate the outcome of secondary intra-ocular lens implantation. Neither a requirement for vitreous surgery nor previous complicated eye surgery/trauma was considered necessarily to be a contra-indication. DESIGN: Retrospective Study. Recruitment was achieved by examination of operating theatre records. SETTING: Teaching Hospital. PATIENTS: 52 out of 54 consecutive cases in whom a secondary lens had been implanted from 1982-1989 under the care of one consultant (BAN). INTERVENTIONS: The medical records of all patients were reviewed and data collected for 52 of the total of 54 patients. MAIN OUTCOME MEASURES: Visual acuity and major complications. RESULTS: 77% of eyes retained the same Snellen visual acuity or better than that pre-operatively and 88% were within one line or better. The Mann Whitney U-test showed that neither vitreous manipulation at the time of secondary lens implantation nor a previous history of trauma had a significant effect on the change between pre- and post-operative Snellen visual acuity. Only one patient developed a retinal detachment and eight had cystoid macula oedema although in only one patient did this account for a final decrease in post-operative visual acuity of more than one line. The most common complication was an intense post-operative uveitis (35%) leading in some cases to indefinite low dose topical steroid treatment (21%). CONCLUSIONS: This technique gives good visual results, even in the disorganised eye, providing the vitreous is adequately managed. However there is a significant complication rate which should be discussed with the patient before undertaking surgery. PMID- 2226984 TI - The visual field in chronic open angle glaucoma: the rate of change in different regions of the field. AB - Using automated perimetry the distribution of visual field loss in 40 chronic open angle glaucoma eyes (40 patients) was found to be predominantly in the nasal, supranasal, and superotemporal regions. The rate of change of visual field threshold values in seven regions of the field was measured by trend analysis over 44.9 +/- 17.9 months. Seventeen eyes had a significant rate of field loss in one or more regions of the field with the remaining eyes either showing improvement or stability. Seven of the 17 eyes with significant regional field loss had stable overall fields. The greatest rate of field loss occurred in the temporal and superotemporal regions. The correlation between the mean threshold value of the initial field test and the rate of change of field over time was significant in the temporal region and of borderline significance in the superotemporal region. The relationship was such that the greater the initial threshold value, the greater the subsequent rate of field loss. PMID- 2226985 TI - The progress of the visual field in chronic simple glaucoma and ocular hypertension treated topically with pilocarpine or with timolol. AB - It is theoretically possible that the vascular effects of topical sympathetic beta-blocking therapy in chronic simple glaucoma (CSG) might tend to neutralise the beneficial effect of a reduced intraocular pressure on the preservation of the visual field. We therefore followed the progress of 422 right eyes and 420 left eyes of 483 patients with CSG and 119 right eyes and 132 left eyes of 151 patients with an original diagnosis of ocular hypertension (OH). These patients were observed for a minimum of one year and up to 13 years, being followed for an average of 5.1 years in the case of CSG and of 4.5 years in OH. The majority of eyes with CSG were treated topically with a miotic and 38% of these received beta blocking therapy in the form of topical timolol. It was concluded that despite suggestions that beta blockers might reduce vascular perfusion of the optic nerve head, which might in turn cause an adverse effect on the visual field progress, the results of this analysis showed that there was less mean deterioration of visual field in eyes treated with beta blocker plus miotic treatment compared with those on miotic therapy alone. PMID- 2226986 TI - Screening for hydroxychloroquine retinal toxicity: is it necessary? AB - All the patients (73) in the Rheumatology Department five year study of second line therapy who have taken hydroxychloroquine (Plaquenil) for rheumatoid arthritis for longer than 18 months were reviewed. These patients have their treatment dosage carefully monitored and have been receiving regular ophthalmic examinations. Most patients still taking the drug were assessed with a battery of tests for evidence of retinal toxicity. No retinal toxicity causing visual loss was found. On the basis of these results and a review of the recent literature we no longer routinely screen patients for hydroxychloroquine retinal toxicity in Cardiff. PMID- 2226987 TI - The development of cataract following trabeculectomy. AB - OBJECTIVE: To determine the risk of cataract development following trabeculectomy. DESIGN: A prospective follow-up study of patients seen pre operatively and at one, three, six and 12 months following surgery and subsequently at yearly intervals. SETTING: Ophthalmology Department of Nottingham University Hospital. PATIENTS: Fifty-seven patients with primary open angle glaucoma, including pseudoexfoliation, undergoing trabeculectomy. MAIN OUTCOME MEASURES: Increases in lens opacity measured by the Lens Opacity Meter 701, the Keeler Projectoscopy and clinical grading. RESULTS: Of 35 patients seen at six months post-operatively, none had lost two Snellen lines of visual acuity due to lens opacity, although three patients showed evidence of increasing lens opacity on all three parameters. CONCLUSION: There is no evidence of visually significant lens opacity occurring at six months post-operative follow-up. PMID- 2226988 TI - Light scatter from the central human cornea. AB - Light scatter from the central human cornea was measured in 60 eyes of 60 patients using computerised image analysis of Scheimpflug slit image photographs. There was no correlation between the amount of scatter and the age of the patients (correlation 0.035, p = 0.79). In addition it was found that light was scattered more at the anterior and at the posterior surfaces of the cornea than from the stroma. PMID- 2226989 TI - Acanthamoeba adherence to contact lenses and removal by cleaning agents. AB - The quantitative adherence of a keratitis isolate of Acanthamoeba polyphaga to low- and high-water content non-ionic soft contact lenses and one type of rigid gas-permeable lens was investigated. Adherence of trophozoite and cyst forms of the organism was observed in vitro, and adherent amoebae counted by a plaque assay method following detachment. Trophozoites adhered to all lens types with adherence being statistically significantly greater to high water content soft lenses. Cyst attachment occurred only to the soft lenses but not to gas-permeable lenses, and was significantly higher for the high water content lenses. Attachment of cysts was significantly lower than that of trophozoites to each lens tested. Recommended cleaning procedures using two commercial solutions removed all adherent trophozoites and cysts from lenses. These studies demonstrate (i) that lenses may act as a vector in Acanthamoeba keratitis, particularly for high-water content lenses and trophozoite amoebae, (ii) that lens cleaning agents may prevent keratitis by removing adherent Acanthamoeba. PMID- 2226990 TI - Precorneal residence times of sodium hyaluronate solutions studied by quantitative gamma scintigraphy. AB - Sodium hyaluronate solutions have been advocated in the management of a variety of dry-eye states. By virtue of their non-Newtonian rheological properties, formulations exhibiting high zero-shear viscosities may be used as an artificial tear with the expectation of prolonged precorneal residence times and improved tolerance. Quantitative gamma scintigraphy was used to evaluate the residence times of 0.2% and 0.3% sodium hyaluronate solutions and a polymer-free solution of buffered saline in 12 patients with keratoconjunctivitis sicca and a group of six normal volunteers. Using several indices of residence time, mean values for the sodium hyaluronate solutions were significantly longer than those for buffered saline. Parallel changes in tear film thickness were also demonstrated using a technique based on laser interferometry. PMID- 2226991 TI - Penetration of topically applied betamethasone sodium phosphate into human aqueous humour. AB - Gas Chromatography combined with Negative Chemical Ionisation Mass Spectrometry (GCMS) was used to determine the absorption of topically applied beta-methasone sodium phosphate into the aqueous humour of human subjects undergoing routine intraocular surgery. The Betamethasone concentration was greatest in the interval 91-120 minutes following topical administration (mean peak concentration = 7.7 ng/ml). At twelve hours post instillation the mean concentration of Betamethasone was 2.5 ng/ml and detectable levels were recorded in the aqueous humour 24 hours after application (mean concentration 0.4 ng/ml). PMID- 2226993 TI - Macrophages related to Bruch's membrane in age-related macular degeneration. AB - This report describes focal thinning of Bruch's membrane in age-related macular degeneration and suggests a role for macrophages in this process. Electron microscopy was performed on four eyes ranging from normal ageing to age-related macular degeneration with early subretinal neovascularisation. As degeneration progressed multiple segments of thinning of Bruch's membrane were observed and macrophages appeared to engulf fragments of the outer collagenous zone. An associated finding at this stage was the shedding of membranous debris by the retinal pigment epithelium and its deposition within Bruch's membrane. This debris forms the basis of soft drusen but in the presence of this material thinning of Bruch's membrane was also observed beneath hard drusen. It is suggested that the widespread accumulation of phospholipid-containing membranes together with the focal concentration of lipid in hard drusen attract macrophages. PMID- 2226992 TI - Autonomic function in Holmes Adie syndrome. AB - Autonomic function was studied in a group of 11 patients with Holmes Adie Syndrome. Autonomic function was assessed by the measurement of cardiovascular reflexes. Heart rate responses to respiration, valsalva manoeuvre and standing were studied. The change in systolic blood pressure on moving from the lying to the standing position was measured. Abnormalities of parasympathetic function were found in three patients, compared with matched controls. Autonomic dysfunction in Holmes Adie Syndrome may be more widespread than previously suspected. PMID- 2226994 TI - Cell culture. PMID- 2226995 TI - A hand-held OKP chart for the screening of glaucoma: preliminary evaluation. AB - Oculo-kinetic perimetry (OKP) uses controlled movements of the patient's eye to position a static test stimulus in the visual field. The test chart consists of a white tangent screen with 23 numbered fixation points located eccentrically at strategic points in relation to a central black spot, which is the test stimulus. As the patient looks at each number in turn, the spot stimulates the retinal areas that are most likely to show early glaucomatous damage. The result is positive if one or more numbers make the spot disappear. Ninety-eight eyes of 54 patients attending a hospital glaucoma clinic were tested with a prototype OKP glaucoma screener and by conventional perimetry. Visual fields plotted conventionally were independently categorised as normal, equivocal and glaucomatous by the perimetrist and the ophthalmologist and these results were further categorised as normal, equivocal or glaucomatous according to whether they were considered abnormal by none, one or both of the observers respectively. The OKP test was positive in (i) 93% of 27 eyes with glaucomatous defects, (ii) 69% of 32 eyes with equivocal loss, (iii) 41% of 39 eyes without previously recognised field loss but having ocular hypertension, a suspicious disc, or contralateral glaucoma, (iv) 9% of 116 eyes from 60 age matched persons accompanying the patients to hospital. If the results were considered in terms of patients not eyes, the OKP test was positive in 85% individuals with glaucomatous field loss in their worse eye and in 12% of the controls. A hand-held OKP chart testing a small set of points and using a constantly exposed stimulus could be a useful tool for the detection of glaucoma in the community. PMID- 2226996 TI - The Oxford modular cataract image analysis system. AB - A modular system of acquisition and analysis of Scheimpflug, retro-illumination and fluorescence images of the in vivo human crystalline lens is described. Image analysis is directed towards the following goals: Scheimpflug slit-images are analysed for: (1) The optical density of nuclear cataract present; (2) The dimensions of the lens and the lenticular zones; (3) The curvatures of the lens and lenticular zones. Retro-illumination images are analysed for: (1) The percentage area which is occupied by cataract; (2) A combined measure (weighted integral) describing both the amount of cataract present and its optical density. Lenticular auto-fluorescence images are analysed for the mean density (fluorescence) of the lens as a whole. A pilot study of the repeatability of the methods is presented. PMID- 2226997 TI - Ocular injury from external rear view mirrors. PMID- 2226998 TI - Headache and sudden collapse in a young man. PMID- 2226999 TI - Response of tumors to thermodynamic stimulation of the immune system. AB - Cytokines such as interferon, interleukin and tumor necrosis factor are natural body defense proteins which have been used individually in recent years to produce a few complete responses of some tumors in a few patients but their overall effect has been limited. The hypotheses is that a biologic stimulus such as endotoxin will stimulate the immune system in a more natural way and hence will be more likely to have an effect especially in the presence of a naturally produced fever than treatment from just one lymphokine. One of the side effects of current lymphokine studies has been fever usually spiking in nature but there has been no obvious effort to relate the extent of the fever to any tumor responses. Clinical experience has shown that increased temperature can enhance the results of radiotherapy and chemotherapy in some situations. Therefore it is logical to put this hypothesis to a test clinically. It is surprising that the combined effect of fever and lymphokine stimulation has not been reported aside from Coley's work, and it is only in retrospect that fever has been suggested to be essential to the tumor control noted. Most of the literature, animal and human, has focused on the destructive effect of temperature on tumor cells and not as part of an immune response to control tumor growth. Endotoxin is the pyrogen on which most current information is available. More effective and more available pyrogens may be developed later. PMID- 2227001 TI - Genetics. PMID- 2227000 TI - Current concerns in the genetics of pregnancy losses. PMID- 2227002 TI - [Response to environmental conditions of extreme driving by the human organism and the stomatognathic apparatus]. PMID- 2227003 TI - [White areas of reticular appearance of the vestibular mucosa]. PMID- 2227004 TI - [Polygraphic examination of dysgnathic subjects undergoing physico-psychic stress. Methodological basis]. PMID- 2227005 TI - [Occlusal analysis of dysgnathic subjects during off road driving. Statement of research and results]. PMID- 2227006 TI - [Monitoring of masticatory muscles with surface EMG before and after off road driving]. PMID- 2227007 TI - [Electromyographic evaluation (EMG) of postural muscles of the neck during off road driving]. PMID- 2227008 TI - [Spectral analysis of electroencephalograms (EEG) before and after off road driving]. PMID- 2227009 TI - [Variations in cardiac rate and arterial pressure during off road driving]. PMID- 2227010 TI - [Fixed prosthetic reconstruction. Restoration of upper incisors. 2]. PMID- 2227011 TI - [Muscular flow and resistance in dentists during work]. AB - In the present paper the advantage of muscular flux and resistance determination in the limb over the traditional cardiovascular parameter about operative stress in dentistry has been discussed. PMID- 2227012 TI - [Training and professional profile of dentistry in the EEC. 5]. PMID- 2227013 TI - [Esthetic dentistry. Perspectives for dental technology]. PMID- 2227014 TI - [Dental technology in Australia. High standard in porcelain technic]. PMID- 2227015 TI - [Development of a process. Pouring titanium in the dental laboratory]. PMID- 2227016 TI - [Soft denture lining material]. PMID- 2227018 TI - [Groove-shoulder-pin attachment. Fourth to ninth milling step]. PMID- 2227017 TI - [Inlays and onlays today. Laboratory completed composite inlay]. PMID- 2227019 TI - [More on the theme comparison and selection of tooth color]. PMID- 2227020 TI - [Total restoration from casting to installation]. PMID- 2227021 TI - [Heratec-system. Layering technic for greater stability]. PMID- 2227022 TI - [Silicoater-MD-process in 2-year clinical test]. PMID- 2227023 TI - [Compatibility of Impresept disinfectant with impression materials]. PMID- 2227024 TI - [New model and duplication system. High tech finishing for greater precision]. PMID- 2227025 TI - [Sensible alternative in preparation of a complete denture?]. PMID- 2227026 TI - [Conceptual preparation of an inlay and onlay partial denture]. PMID- 2227027 TI - [Chewing movements, foundations and basic relations of occlusal arrangements in practice]. PMID- 2227028 TI - [Experimental method of judging heat fast porcelain restorations]. PMID- 2227029 TI - [Curiosities and amusements. Laboratory applications and their results]. PMID- 2227030 TI - [Better quality in poured alloy models by supplementary seed crystals]. PMID- 2227031 TI - [Cyclarc-system. Titanium pouring in dentistry]. PMID- 2227032 TI - Removable partial overdentures. PMID- 2227033 TI - Philosophies and principles of removable partial overdentures. AB - Retention of remaining teeth for use as overdenture abutments has been widely used in the discipline of complete denture therapy, but has frequently been overlooked as a means of enhancing removable partial denture therapy. There are considerable advantages in retaining even severely compromised teeth that can be included in a treatment plan for providing removable partial overdentures. The value of such teeth in providing aesthetic improvement, residual bone retention, denture base support, primary or secondary retention, and improved stability should be of primary importance in treatment planning. PMID- 2227034 TI - The overdenture concept. AB - The biomechanical rationale for the treatment of patients with overdentures, and their advantages and disadvantages are presented. The indications and contraindications for the treatment of partially edentulous patients with removable partial overdentures are discussed. The patient's and dentist's responsibilities for the success of therapy are enumerated. PMID- 2227035 TI - Classification of removable partial overdentures. PMID- 2227036 TI - Removable partial overdentures. Clinical considerations. AB - Removable partial overdentures have the potential for salvaging teeth with poor prognoses and using them for prosthesis support and retention. Careful case selection and creative treatment planning can lead to aesthetic, well-supported restorations for a variety of patients with compromised dentitions. PMID- 2227037 TI - Design, preparation, and maintenance of overdenture abutments. PMID- 2227038 TI - Endodontic considerations in restoration of partial overdenture abutments. AB - Overdenture abutment teeth often require endodontic treatment. Various factors, such as status of the pulp, periodontal state of the tooth, and the sequence of overdenture treatment, influence endodontic management of the patient. After completion of endodontic treatment, the coronal part of the root filling is removed, leaving an adequate amount of the root filling in the apical part of the root canal undisturbed. The abutment tooth is then permanently restored with a filling material, or is prepared for a cast restoration. PMID- 2227039 TI - Periodontal considerations of the removable partial overdenture. AB - 1. An overdenture, whether complete or partial, is an excellent mode of treatment in the mutilated dentition for the preservation of the residual ridge. 2. Selection of patients for an overdenture should be based on past history of dental neglect, the status of the teeth and their periodontium, including present oral hygiene status, and patient motivation. The patients with a history of dental neglect, poor oral hygiene, and lack of motivation in having the teeth and the periodontium restored to health as well as strict compliance to a home-care regimen and recall schedule are not good candidates for treatment with an overdenture. 3. The choice of teeth or roots to serve as overdenture abutments must include their periodontal evaluation, which should consist of a detailed periodontal examination, diagnosis, prognosis, and treatment when this is indicated, including chemical protection (fluoride gel) and an oral hygiene regimen tailored to individual needs. 4. The knowledge and expertise in the selection and implementation of appropriate periodontal treatment modalities is of paramount importance in restoring optimum periodontal health to the overdenture abutments before overdenture fabrication. 5. The maintenance phase of the overdenture abutments as well as of the existing natural teeth is of critical importance in the preservation of health of these abutments and teeth. This maintenance phase should consist of periodic recalls based on individual needs; a detailed periodontal evaluation, including patient's motivation and status of oral hygiene and denture hygiene; and detection of caries. If necessary, appropriate periodontal and/or restorative therapy should be performed, and oral hygiene measures reinforced. This will ensure longevity of both abutment teeth or roots and of the existing natural teeth resulting in a long-term success of an overdenture. 6. Because there is evidence of high incidence of periodontal disease and dental caries in overdenture wearers, and because this evidence is attributed mainly to lack of motivation and compliance of adequate oral hygiene as well as to frequency of recall visits, patients should be made aware of the importance of their role in the maintenance phase of treatment and in the factors that lead to ultimate success of overdenture therapy. 7. With (a) proper selection of the patient and the abutment teeth, (b) adequate periodontal and restorative health and treatment to ensure optimum health prior to RPOD construction, (c) a well-designed home-care regimen and frequency of recalls, and (d) proper execution of maintenance care, changes for long-term success of overdenture therapy will be much improved. PMID- 2227040 TI - Removable partial overdentures with mechanical (precision) attachments. AB - Mechanical attachments for overdentures have been available in various forms for over a century. The explosive interest in osseointegration and the effort on the part of the profession to avoid the complete denture as a treatment modality has stirred the interest in positive retentive elements for overdentures represented by the mechanical stud and bar attachments. The cited references provide a resource as a trouble-free guide in the selection and use of the various stud and bar attachment systems. The clinical examples show a pattern of application not generally discussed by the manufacturers, illustrating the simplicity of use with the options for all attachments including magnets. The discussion on magnets comes from 9 years of clinical experience. Rare earth magnets provide excellent adjunct retention, and their assembly follows the same protocol and complexity as stud attachment systems. All magnets, at the present state of the art, have a corrosion potential with the exception of the Laser Sealed Units (Golden Dental, Golden, CO). Finally, the mechanics of the attachment overdenture serves as an excellent training field for the osseointegrated prosthesis, be it the classic Branemark (Nobelpharma USA, Chicago, IL) restorative or the implant overdenture concept. PMID- 2227041 TI - Overdentures with magnetic attachments. AB - Magnets were used only occasionally for dental purposes several decades ago. Since the advent of rare earth magnet alloys, however, intraoral magnets are shaping the course of aesthetics and retention for both complete and removable partial overdentures. Their benefits include simplicity, low cost, self adjustment, inherent stress breaking, automatic reseating after denture displacement, comparative freedom of lateral denture movement, a low potential for trauma to the retained roots, and elimination of the need for adjustment in service. The clinical procedures involved in their application do not require any special skills, and the options offered by the various manufacturers give the dentist a wide variety of choices in selecting an appropriate treatment plan. Clinical experience has shown that magnetic retention offers an economical alternative for teeth that would otherwise require expensive or extensive restorative treatment, and can be used as an effective and often superior replacement for failed bridgework. Finally, it is clear that overdenture treatment per se is a valuable option for the dentist, and the use of magnets expands this option to the retention of tooth roots that might otherwise be scheduled for extraction. The natural tooth root, even if periodontally involved, can serve as a useful aid in denture support and retention, and should be regarded as at least as good as, and in most cases superior to, an implant. It is also much less expensive. PMID- 2227042 TI - Removable partial overdentures with natural root structure and osseointegrated fixtures. AB - The development and refinement of osseointegration have had primary impetus in treatment of the totally edentulous patient. The same principles, however, may be applied to the partially edentulous patient. Osseointegrated fixtures used in conjunction with mechanical or magnetic attachments may be used to construct partial or full overdentures. This allows treatment with removable prosthodontics in many cases in which it is not practical to achieve anchorage for a fixed prosthesis. PMID- 2227043 TI - Overdentures and osseointegration. Case studies in treatment planning. AB - Prosthodontic considerations in the treatment planning and treatment of the overdenture patient have been described within the context of osseointegration. The rehabilitation of patients with a minimal number of teeth remaining represents an increasingly interesting challenge because of the introduction of osseointegration into the clinical armamentarium. As demonstrated through case reviews, a clinician cannot be limited to osseointegration procedures alone. Conservative tooth-supported complete and partial overdentures represent not only viable alternatives, but in some instances will be the treatment of choice. Expertise in both modalities will be required to treat the patient with limited dentition. PMID- 2227044 TI - Removable partial overdentures for special patients. AB - Removable partial overdentures are an option that should be considered by every dentist who is involved with cosmetic dentistry or dentistry for the older adult. The rationale, indications, and technique have been described for providing an aesthetic, functional prosthesis that is also conservative in nature. The reversibility of the procedure allows the patient the opportunity to pursue other forms of treatment should the result not meet his or her expectations. For appropriately selected special patients, the results can be extremely gratifying for both the patient and dentist. PMID- 2227045 TI - Removable partial overdentures for the irradiated patient. AB - Patients who have received radiotherapy to the head and neck area must avoid dental extractions and seek simplicity in treatment and home care follow-up. For partially edentulous patients, removable partial overdenture therapy can fulfill these goals while maintaining the high level of function and aesthetics desired by patients. PMID- 2227046 TI - [Mechanism of action and therapeutic use of cyclosporin A. Experimental and clinical experiences in dermatology]. AB - The clinical application of cyclosporine A caused many success in transplantation surgery as well as in the treatment of (auto-) immune disorders. The biological highly active substance differs from conventional immunosuppressive drugs (i.e. steroids, azathioprine) by it's selective action on T-lymphocytes. However, current experimental findings indicate a direct influence on epidermal keratinocytes, too. First therapeutical experiences, concerning systemic and topical application in different skin diseases are summarized. PMID- 2227047 TI - [The cytotoxic effect of anti-Ro- (SS-A) antibodies and UVA light on human endothelial cells in vitro]. AB - There is in photosensitive lupus erythematosus a strong association of high titers of anti-Ro(SS-A) antibodies in the serum of the patient with the development of special skin reactions depending on UV-light. The aim of our experiments was to detect a cytotoxic effect of anti-Ro(SS-A) antibodies and UVA light on human endothelial cells in vitro (standard trypan blue exclusion test, SEM). After UVA-doses of 1 to 100 J/cm2, which were tested, and influence of serum containing anti-Ro(SS-A) antibodies (62 E, ELISA) membrane destructions of endothelial cells depending on the UVA-dose can be seen, irrespective of the fact whether the antibodies are present throughout the irradiation or added afterwards. This cytotoxic reaction depends on complement. A UVA-dose of 100 J/cm2 causes lethal damage of 40% of the cells. These results were confirmed by scanning electron microscopy. PMID- 2227048 TI - [8-MOP serum level profile following administration of Geroxalen to patients with psoriasis and a control group]. AB - After 8-MOP application (Geroxalen) the mean serum levels with 11 single values over 8 hours from 21 psoriatics with squamous infiltrative plaques do not differ from serum level curves of 46 healthy volunteers (Psoriatics: maximum plasma level cmax 189 nm 8 MOP/ml serum at the time tmax 1,2h; area under the curve AUC0 8 284 ng.ml-1.h. CONTROL GROUP: cmax 193 ng 8 MOP/ml serum; tmax 0.9h; AUC0-8 290 ng.ml-1.h). A malabsorption of 8-MOP in psoriatic patients could not be found in our study, although this is described for fat among other. PMID- 2227049 TI - [8-methoxypsoralen serum content of problem patients in PUVA therapy]. AB - Beside the stage, expression and course of psoriasis as well as the compliance of patients low or abnormal 8-MOP levels are the cause of the ineffectiveness of the PUVA-therapy, as we could demonstrate in 7 of 11 problem cases. Thus, we determined only a maximal 8-MOP concentration of 47 ng/ml serum as an extreme value in one patient and on other patient had his maximal serum peak 3-4 hours after 8-MOP-application and only a value of 8-MOP of 18 ng/ml serum at the recommended time of irradiation. In this connection a first pass mechanism for 8 MOP by a limited biotransformation capacity in the liver is significant and one basic reason for the interindividual variation. Therefore in these cases the knowledge of the individual serum profiles of 8-MOP is helpful to adapt the time of irradiation to the individual necessities and/or to increase the 8-MOP doses. PMID- 2227050 TI - [Multiple daily ultrasound treatment of patients with progressive systemic scleroderma]. AB - Inpatients with progressive systemic scleroderma were submitted to ultrasound application several times every day. This type of ultrasonic therapy is practicable. Pain decreased in 18 of 24 patients. At the end of therapy, pain had not increased in any of the patients. The strength of the hands was significantly improved in all patients. PMID- 2227051 TI - [Results of treatment of malignant melanoma--a computer analysis of 772 patients]. AB - The data of 772 patients with malignant melanoma, treated from 1.1.1972 to 30.6.1988 in the Regional Hospital Dresden-Friedrichstadt were analysed by computer. The probability of survival was estimated separately by the method of Kaplan and Meier in dependence on clinical stage in the time of the first treatment, pT and sex. The 10-year survival rate in clinical stage I amounts to pT1 = 100%; pT2 = 82.9% +/- 4.0%; pT3 = 67.1 +/- 4.3% and pT4 = 58.0 +/- 4.7%. There are significantly differences between women and men with melanomas of the category pT2 and pT3 in favour of women (pT2: 88.6%:70.0%; pT3: 75.8%: 53.4%). In the cases of pT4 melanoma there are no differences (61%:53%). The average time of survival from these patients who have died from melanoma shows also marked differences according to pT (pT2 = 46.6 month, pT3 = 36.6 month, pT4 = 30.2 month). PMID- 2227052 TI - [Histology of UV-induced epidermis reactions. 1. A contribution to the differentiation of sunburn cells]. AB - The UV-induced reaction of the epidermis is marked be extra- and intracellular edema and intraepidermal vesicles. Characteristical is the appearance of sunburn cells. In semithin section they can be differentiated in two cell types: "fried egg cells" prevail as early type in the exsudative phase (type I), "dark cells" as late type in the degenerative phase (type II) of the UV-reaction. PMID- 2227053 TI - [Initial results of the long-term effect of PUVA therapy in lichen ruber of the mouth]. AB - In a study involving 77 patients affected by lichen ruber lenticularis oralis, the relative clinical long-term healing rate was determined after application of a "Systemic Mouthmucosal Photochemotherapy" (SMPT). The results obtained showed that 78.5 percent of the patients were cured while the disease recurred in 21.5 percent of the patients. Against of 12 patients with erosive Lichen ruber oralis have had 9 patients an recidive post Re-SMPT. PMID- 2227054 TI - Lichen ruber and bullous pemphigoid. AB - The authors describe the case of a male patient, 20 years old, with a rapidly developing picture of disseminated lichen ruber planus together with the formation of vesicles and blisters. Immunofluorescent examination demonstrated lichen ruber associated with bullous pemphigoid. A good therapeutic effect was obtained with a combination of Triamcinolon and Tigason. PMID- 2227055 TI - [Photo-photochemotherapy with the "Theralum" UV whole body therapy equipment]. PMID- 2227056 TI - [Modification of various cell functions of lymphocytes and granulocytes in vitro by 8-MOP without activating UVA irradiation]. PMID- 2227057 TI - [Keratolytic therapy]. PMID- 2227058 TI - [Commentary on the new AIDS guideline and on the 4th regulation of implementation]. PMID- 2227059 TI - [Hyde's nodular prurigo--preference for creases of the skin]. AB - The arrangement of papules in prurigo nodularis Hyde along the cleavage lines of the skin, but not Blaschko's lines, supports the classification of prurigo nodularis Hyde as a traumatic chronic papulosis with cutaneous neural hyperplasia of xerodermal skin. PMID- 2227060 TI - [The effect of monochromatic and polychromatic UV irradiation and of 8-MOP on phagocytosis of neutrophilic granulocytes]. AB - We investigated the inhibition of granulocyte phagocytosis by 8-MOP and monochromatic or polychromatic UV light. After application of 8-MOP and UV there was an additional inactivation compared with UV alone, as expected from studies on other cell species. This additional inhibition of phagocytosis was found to be increasing with 8-MOP level. The action spectra of granulocyte inactivation by 8 MOP and UV involves the investigated UVB range (until 300 nm). A marked inactivation of granulocytes was seen after erythemogenic fluences only. Therefore we assume that inactivation of granulocytes by direct UV action does not play an essential role in UV therapy in vivo. PMID- 2227061 TI - [Kinship studies in Gorlin-Goltz syndrome (basal cell nevus syndrome)]. AB - By means of an investigation on 7 patients from 3 families views are expressed on the problems of the basal cell-naevus-syndrome. The typical clinical signs appear preferentially and as first-symptoms in the jaw-bone as solitary and later developing multiple cysts. Because these first symptoms of the syndrome cause secondary, dentitio tarda (belated dentition) and displacement of the teeth, the dentist or the maxillo-facial-surgeon has a special responsibility for early diagnosis of this disease. Reference is made to the necessity of interdisciplinary cooperation and the ambulatory-care of the patients in the sense of a family registration and observation. PMID- 2227062 TI - [Leukoplakia-like epidermal nevus of the mouth mucosa. Case report]. AB - We report on a nevus of the oral mucosa, which became present in the age of 30 of a male patient. By microscopic examination we did not find any vacuolation of the spinous layer of the epithelium. So this nevus has been considered quite different from the typical white sponge nevus, and we prefer to name it leucoplakial nevus of the oral mucosa. PMID- 2227063 TI - [Pamphlet on the treatment of psoriasis with 8-methoxypsoralen tablets and UV light (PUVA therapy)]. PMID- 2227064 TI - The use of calcium channel blockers in obstetrics and gynecology; a review. AB - Since their introduction, calcium channel blockers gained wide use in the treatment in various fields of medicine. Calcium channel blockers were shown to inhibit contractions of the pregnant and nonpregnant uterus, and lately their properties have made it, theoretically, an ideal candidate for the use in severe pregnancy-induced hypertension: it is effective in lowering blood pressure, has a fast and long-standing action, may be conveniently administered via the oral route, and it is not associated with serious side effects. PMID- 2227065 TI - Influence of pregnancy on human immunodeficiency virus disease. AB - Over a period of 3 years (mean 16, extremes 3 and 36 months), we compared clinical and laboratory parameters of 128 female, human immunodeficiency virus (HIV)-infected patients, all in clinical stage II or III (CDC classification). 34 patients were pregnant and delivered a viable infant after at least 28 weeks of amenorrhea (group I), 29 patients were pregnant and had a spontaneous or induced abortion during the first or second trimester (group II), and 64 were non pregnant female control patients (group III). The changes in the clinical stages over time were not statistically significant between the groups. The only laboratory parameters that were significantly higher in group I at the time of the delivery were: leucocyte count (p less than 0.001), lymphocyte count (p less than 0.05), and sedimentation rate (p less than 0.001). These changes are known to be related to pregnancy and not to HIV disease. All other laboratory parameters showed no significant differences within and between the groups. We conclude, that pregnancy--carried to term or interrupted--does not aggravate the natural evolution of HIV infection in clinical stage II and III patients. PMID- 2227066 TI - Female sterilization failure after bipolar electrocoagulation: a 6 year retrospective study. AB - A 6 year retrospective study was conducted from January 1983 till December 1988. During this period there were 13,014 births, 1,776 registered spontaneous abortions and 200 tubal pregnancies. 1,437 sterilizations were performed in the same period via bipolar electrocoagulation. 11.5% of the ectopic pregnancies were in patients who had previously undergone a tubal sterilization. The failure ratio following bipolar coagulation was 1.18%, and all failures were extra-uterine pregnancies, with an average interval between sterilization and ectopic pregnancy of 28.8 months. This reflects the importance of previous sterilizations as an etiologic agent in ectopic gestations. We will discuss the possible etiological factors for our sterilization failures and how these failures can be avoided or minimized. Also diagnostic difficulties and management of an extra-uterine pregnancy (EUP) following sterilization will be presented. PMID- 2227067 TI - The pin-hole cervical os; a small fertility problem. AB - 24 women with a so-called pin-hole cervical os during the pre-ovulatory phase of the menstrual cycle were detected in a group of 850 infertile couples. This cervical condition is rarely seen and is often combined with extreme oligomucorrhea and poor cervical mucus qualities. Sperm quality was so poor in four couples that they were excluded. Nine women were likely to have been exposed to diethylstilbestrol (DES) in utero. The pregnancy rate in this group was poor, only two pregnancies by coitus and none by intra-uterine AIH. In the other eleven women there was a strong correlation between a good result of the post-coital test (PCT) and the chance to achieve pregnancy. Four of the eight women with a good result of the PCT became pregnant by coitus. The three women with a poor result of the PCT became pregnant by intra-uterine AIH. It is possible that the fertility prognosis of a woman with a pin-hole cervical os during the pre ovulatory phase of the menstrual cycle is unfavourably influenced by DES exposure in utero. A pin-hole cervical os in the pre-ovulatory phase of the menstrual cycle, without DES exposure, has probably no influence on fertility. PMID- 2227069 TI - Predictive values of CA 125 antigen levels and CT scan in second-look procedures for ovarian cancer. AB - 23 patients with ovarian cancer were investigated 10 days after their last regimen of chemotherapy by CT scan and CA 125 in comparison with 'second-look' findings. In 17 out of 23 cases the CT scan results correlated with the operative ones. There were 6 false-negative findings but no false-positives. In all cases serum CA 125 levels correlated with the second-look operation. Our data suggest that the upper limit of CA 125, especially for patients, with negative findings, is less than or equal to 20 U/ml which is much lower than that of 35 U/ml, which is generally accepted. They also indicate the value of CA 125 in the detection of persistent ovarian cancer and the value of the CT scan in the detection of liver metastases. According to the above findings we question the value of the second look operation in certain cases of ovarian cancer. PMID- 2227068 TI - Hormonal postcoital contraception with an ethinylestradiol-norgestrel combination and two danazol regimens. AB - The ethinylestradiol-norgestrel combination (EE-NG) for postcoital contraception, as described by Yuzpe, has been shown to be an effective method but with frequent side effects. To overcome the problem of adverse effects a new approach using danazol was proposed, but the efficacy and acceptability of this treatment have not yet been tested in large studies. In a 5-year period at the AIECS Family Planning Centre in Milan we treated 2448 women requesting postcoital contraception using Yuzpe's regimen and two danazol regimens (800 mg/1200 mg). The patients' acceptability for danazol treatment was higher than for Yuzpe's regimen due to fewer, milder and shorter side effects. Nine pregnancies occurred in the EE-NG group (2.21%), 17 in the 800 mg group (1.71%) and 6 in the 1200 mg group (0.82%). Our study shows a statistically significant efficacy against expected pregnancy rates both with Yuzpe's regimen and with danazol. The 1200 mg danazol treatment seems to be more effective and can be considered a valid alternative to the EE-NG combination for hormonal postcoital contraception. PMID- 2227070 TI - Comparative study of RIS with the 131I-OC 125 F(ab')2 Mab and CT scan prior to second look operation for ovarian cancer. AB - A tumour-associated radiolabelled monoclonal antibody (Mab) 131I-OC 125 F(ab')2 was used to investigate 27 patients 2 weeks after their last chemotherapy regimen and prior to second-look surgery for ovarian cancer. We did compare the radioimmunoscintigraphy (RIS) findings with the CT scan results and the second look operation data. In 23 out of 27 cases the RIS results correlated with the operation findings, while there were four false-negative results. Computed tomography (CT) scans correlated in 17 out of 23 cases with the operative findings, while there were six false-negative results. We concluded that RIS is more specific in detecting the tumour site within the pelvis, while CT scan is superior in detecting liver metastases. PMID- 2227071 TI - Female urinary incontinence: comparative value of history and urodynamic investigations. AB - In order to identify the role of urodynamic investigation in relation to urinary symptoms, the authors assessed the diagnostic value of history and of urodynamic investigation in female urinary incontinence. 154 patients presenting with urinary incontinence were investigated prospectively, by standardised history and investigation of bladder stability and investigation of bladder stability and of cervico-urethral closure function. Clinical and urodynamic diagnostic conclusions were compared. Urodynamic results were highly discordant in the presence of clinical 'erethism', whilst agreement was more marked in the case of stress incontinence. Urodynamic investigation may be indicated after failure of medical treatment in the case of 'dysfunction'. By contrast, it is essential in stress incontinence in order to identify the mechanism or detect subclinical 'dysfunction'. PMID- 2227072 TI - Advanced combined intra-uterine and ovarian gestations: case report. AB - Combined intra-uterine and ectopic gestations are uncommon. Heterotopic gestations in which the ectopic pregnancy is located in the ovary are exceptional. We are reporting a 22 week heterotopic gestation with two live fetuses, one fetus was developing in the uterus and one in the ovary. Surgical excision of the ovarian pregnancy was conducted without disturbing the intra uterine live fetus who was ultimately delivered uneventfully at term. PMID- 2227073 TI - Determination of plasma concentrations of cyclandelate and mandelic acid in patients with generalized atherosclerotic vasculopathy treated with oral cyclandelate. AB - Cyclandelate, a vasoactive substance consisting of the mandelic acid ester of 3,3,5-trimethylcyclohexanol, was administered to 10 patients with cerebrovascular and/or peripheral vascular disease. Blood specimens were collected at 1-6 h after oral administration of 1600 mg cyclandelate, and the ester and acid were extracted from plasma in acid medium using n-hexane/isopropyl alcohol. The concentrations were determined by a high-performance liquid chromatography isocratic system. The highest plasma cyclandelate concentrations were detected at the third hour, whereas plasma mandelic acid concentrations were still increasing 6 h after administration. PMID- 2227074 TI - Controlled-release theophylline in the treatment of nocturnal asthma. AB - A total of 104 asthmatic patients with symptoms of asthma and/or a 'morning dip' in the peak expiratory flow rate (PEFR) who were receiving multiple therapies, including inhaled or oral steroids, were treated in addition once nightly with controlled-release theophylline in an 8-week double-blind, placebo-controlled cross-over study. Theophylline produced an improvement in symptoms of cough, wheeze, sleep disturbance and PEFR in the 73 completing patients compared to run in and placebo treatment. Theophylline also produced an improvement in the forced expiratory volume in 1 s and forced vital capacity relative to baseline, and in the difference between actual and predicted PEFR values. Nausea was the most frequent side-effect but both patients' and investigator's global impressions of the effect of study medication were in favour of theophylline. PMID- 2227075 TI - Oral and intravenous pharmacokinetic profiles of doxofylline in patients with chronic bronchitis. AB - Serum doxofylline concentrations were evaluated after solid-phase extraction by high-performance liquid chromatography following administration of 100 mg doxofylline given as a single intravenous dose over 10 min or 400 mg doxofylline given orally twice daily for 5 days in six and eight non-smoking, fasting, chronic bronchitic patients, respectively. Doxofylline possessed a very short distribution phase following intravenous administration, with a sustained elimination phase (half-life 1.83 +/- 0.37 h). After oral administration, the peak serum doxofylline concentration was 15.21 +/- 1.73 micrograms/ml and the mean elimination half-life was 7.01 +/- 0.80 h; there was a large inter-subject variability. No side-effects were experienced by the patients during the study. PMID- 2227076 TI - Steatorrhoea in cirrhosis: effect of ursodeoxycholic acid administration. AB - In a double-blind, crossover study, 10 cirrhotic patients (Child B rating) with steatorrhoea (daily output of faecal fat greater than 8 g) and dyspepsia were placed on a controlled diet for 14 days. Patients then received 150 mg ursodeoxycholic acid (UDCA) or placebo twice daily for 14 days. Faecal fat excretion was reduced from 14.7 to 10.6 g/day by UDCA and dyspepsia symptom scores were also reduced. Serum aspartate aminotransferase concentrations declined significantly (P less than 0.02) following UDCA treatment, whereas serum bile acid levels increased from 35 to 40.5 microM and the percentage of UDCA increased to 22%. It is concluded that UDCA may be useful for many of the symptoms present in patients with liver cirrhosis. PMID- 2227077 TI - Ketorolac, a new non-opioid analgesic: a double-blind trial versus pentazocine in cancer pain. AB - A randomized double-blind trial was performed to evaluate the efficacy of a new non-steroidal anti-inflammatory analgesic drug, ketorolac, in the treatment of cancer pain compared with the opioid pentazocine. A total of 40 patients with moderate to severe cancer pain were studied, 20 patients being treated with 10 mg ketorolac given orally every 6 h and 20 receiving 50 mg pentazocine given orally every 6 h for up to 7 days. A reduction in the severity of the pain was recorded in both treatment groups with no significant difference in efficacy being found between the two therapies, although withdrawals due to adverse reactions were significantly less in the ketorolac-treated group (p less than 0.005). It is concluded that ketorolac may be a useful and more acceptable alternative to opioids in the treatment of cancer pain. PMID- 2227079 TI - Pharmacokinetics and therapeutic study with nimesulide suppositories in children with post-operative pain and inflammation. AB - The pharmacokinetic pattern of 100 mg nimesulide administered rectally at different times prior to undergoing minor surgery was studied in 45 children. Absorption of nimesulide was relatively fast, a peak plasma concentration of 75 mg/l being reached 3 h after administration, and the elimination half-life was 3.15 h. The efficacy and tolerability of the nimesulide suppositories were assessed in a randomized, double-blind, dipyrone-controlled study of 50 children suffering from moderate to severe post-operative pain, the drugs being administered one to three times daily as required; 26 patients received nimesulide and 24 dipyrone. A consistent reduction in pain was recorded during nimesulide therapy given for a mean period of 2.5 days, with a mean consumption of 3.5 suppositories. Similar results were obtained in dipyrone-treated patients. The efficacy of both drugs was judged by the physicians to be good or very good in 70% of cases and there were no statistically significant differences between the two treatment groups in the dosage required or the pain relief. Tolerability of both drugs was excellent, with only one patient in each treatment group complaining of nausea. PMID- 2227080 TI - Treatment of respiratory tract infections in children: a study of a combination of amoxycillin and clavulanic acid. AB - In an open study, 70 in-patients and 23 out-patients aged between 1 and 14 years with sinusitis (n = 1), perforated otitis media (n = 4), pharyngotonsillitis (n = 25), tracheobronchitis (n = 30) or broncho-pneumonia (n = 33) were treated daily with a combination of 40 mg/kg amoxycillin and 10 mg/kg clavulanic acid in three equal doses for between 6 and 15 days. Purulent specimens were cultured when obtainable and pathogenic organisms identified were Staphylococcus aureus, beta haemolytic streptococcal group A, Pseudomonas aeruginosa, Pseudococcus species and Klebsiella pneumoniae infections, of which 45.7% were beta-lactamase producing and 54.3% were ampicillin-susceptible. After treatment, only one beta lactamase-producing Streptococcus and one Staphylococcus infection persisted. Side-effects (vomiting, nausea, diarrhoea, maculopapular exanthema, rash) occurred in 16 patients and treatment was withdrawn in eight. It is concluded that the amoxycillin--clavulanic acid combination is a suitable first choice for the treatment of respiratory tract infections in children in whom the pathogenic organism may not have been established. PMID- 2227078 TI - Placebo-controlled comparison of single intramuscular doses of ketorolac tromethamine and pethidine for post-operative analgesia. AB - The analgesic efficacy and safety of single doses of 10 mg and 30 mg ketorolac tromethamine and 100 mg pethidine were evaluated in a double-blind, parallel group study. The drugs were administered intramuscularly to patients experiencing moderate, severe or very severe pain immediately following major abdominal surgery. A total of 129 patients were randomly assigned to receive either active drug (n = 32 for each treatment group) or placebo (n = 33), and the patients assessed pain intensity and pain relief on a visual analogue scale at regular intervals over the following 8 h. During the first 2 h, pethidine had a more rapid onset of action than ketorolac or placebo, and thereafter 100 mg pethidine and 30 mg ketorolac were equally effective. Ketorolac, at a dose of 10 or 30 mg, and 100 mg pethidine were clinically and statistically more effective than placebo, with 30 mg ketorolac having a similar efficacy to 100 mg pethidine over the 8-h study period and 10 mg ketorolac being slightly less effective than 30 mg ketorolac. No serious adverse events were reported. PMID- 2227082 TI - Photodamaged skin: clinical management with topical tretinoin. Proceedings of a satellite symposium to the 1st congress of the European Academy of Dermatology and Venereology. Florence, 26 September 1989. PMID- 2227081 TI - Short- and long-term effect of nifedipine on the visual field in patients with presumed vasospasm. AB - It is assumed that the ocular circulation may be involved in the vasospastic syndrome and patients with vasospasm have visual field defects that are neither ophthalmologically nor neurologically explainable. A retrospective study showed that 20 mg sustained-release nifedipine treatment given orally may be helpful in these cases. There was a marked short-term effect in cases with proven peripheral vasospasms but not in similar cases without such vasospasms. The study also showed that the effect could last for up to 12 months when 20 mg nifedipine was given twice daily but the long-term effect was slightly less than the short-term effect. A number of patients had to discontinue nifedipine treatment due to side effects. PMID- 2227083 TI - Topical tretinoin research: an historical perspective. AB - The topical tretinoin epoch began almost 30 years ago in the laboratories of Stuttgen where he first recognized that a vitamin A derivative, tretinoin, had the potential to be a truly significant form of dermatological therapy. His early clinical trials in a variety of skin disorders provided the first indication of topical activity for the retinoids. Kligman evaluated further the utility of topical tretinoin; focusing his attention on acne. Through these initial studies, topical tretinoin became a fundamental treatment modality for acne. Soon after topical tretinoin was made available, elderly patients using it to treat acne noted a general improvement in the quality of their skin. Kligman began open clinical trials to investigate the effects of topical tretinoin on treatment of photodamaged skin. Positive findings from these trials led to double-blind, vehicle-controlled pilot studies which supported the concept that topical tretinoin could improve the fine wrinkling, mottled hyperpigmentation and tactile roughness which are characteristic of photodamaged skin. These results were verified in two large double-blind, multicentre studies of approximately 700 patients that used not only clinical and patient evaluations but also biopsies and skin surface replicas. PMID- 2227084 TI - Photodamaged skin: a medical or a cosmetic concern? AB - A well-tanned skin is currently regarded as a sign of fitness, youth and health, with people increasingly exposing their skin to the sun and using tanning accelerators, such as psoralens, but exposure to ultraviolet B (UVB) radiation from the sun causes extrinsic ageing of the skin. The minimal erythema dose is rarely exceeded but the UVB dose that brings about irrepairable DNA damage leading to photodamage is lower. Growing numbers of patients, therefore, have prematurely aged skin with pigmented spots, dryness, itchiness and wrinkles. These symptoms are more than just of cosmetic concern. It is known that epitheliomas frequently develop in photodamaged skin; consequently, this skin requires medical treatment. Prophylactic measures should be taken from childhood, but an effective treatment for already damaged skin is topically applied tretinoin, which should be used with a mild skin cleansing and skin care programme. PMID- 2227085 TI - Clinical effects of long-term therapy with topical tretinoin and cellular mode of action. AB - In a double-blind, placebo-controlled study, 0.1% topical tretinoin reduced the effects of photo-ageing maximally after 10 months, with no further improvements if treatment was continued until 22 months. Topical tretinoin induced epidermal hyperplasia, compaction of the stratum corneum and the deposition of ultrastructurally visible collagen fibrils in the papillary dermis. It also reduced the number and activity of melanocytes, and possibly induced angiogenesis. An Alcian Blue-positive glycosaminoglycan-like substance was detected in the stratum corneum of tretinoin-treated skin and mitoses were significantly increased. The cellular changes brought about by tretinoin may, in part, be the basis for the clinical improvement in photo-aged skin brought about by tretinoin. PMID- 2227086 TI - Methods for the assessment of the effects of topical retinoic acid in photo ageing and actinic keratoses. AB - Quantitative techniques for assessing the effects of tretinoin on photo-aged skin mainly involve humans, although hairless mice were used in initial studies. Ideally techniques should be non-invasive but occasionally biopsies have to be taken, especially when studying the effects of tretinoin on different skin compartments. Characteristic features of photo-aged skin, including the development of fine and coarse wrinkles, skin discoloration, rosy cheeks and telangiectasis, have been assessed subjectively using a visual analogue scale. Effects of tretinoin on wrinkle depth have been measured non-invasively by quantifying contours of silicone rubber replicas using either a mechanical tracking device or an optical technique employing an image-analysing computer. Changes in skin colour have been measured using an erythema meter and the stimulatory effect of tretinoin on blood flow has been established by laser doppler flowmetry. Skin thickness has been measured non-invasively using pulsed A scan ultrasound which showed that tropical tretinoin increased thickness. Biopsies have also been used but no changes in the thickness of the dermal repair zone have been noted in humans, in contrast to the situation in hairless mice. Epidermal dysplasia has been measured by a visual analogue scale or by objective image analysis. PMID- 2227087 TI - Clinical efficacy and patient tolerance of topical tretinoin therapy in photo ageing. AB - A total of 89 patients (mean age 42 years) with clinical signs of photo-ageing were evaluated in an open study to determine the clinical efficacy and tolerance of topical tretinoin therapy. Each evening for 6 months about 1 cm of cream containing tretinoin was applied to the face. Patient compliance and tolerance were maximized by gradually increasing the tretinoin concentration in the cream over the treatment period: 0.01% tretinoin for 1 month, then 0.025% for 1 month and finally 0.05% for 4 months. By the end of the 6 months' treatment period, 95.8% of patients showed improvement in the clinical symptoms of photo-ageing (coarse and fine wrinkling, skin thinning, mottled hyperpigmentation and laxity), except for xerosis. During treatment, 17 (19.1%) patients withdrew from the study, in five (5.6%) this was due to treatment-related side-effects. Patient compliance was rated as excellent in 47.0% of cases, good in 48.5% and fair in 4.5%; tolerability was excellent in 51.4% of cases, good in 44.4% and fair in 4.2%. Improvements were confirmed by scanning electron microscopy, computerized profilometry and computerized image analysis of skin replicas of the same areas taken before and after treatment, with a reduction in width and depth of wrinkles, improved skin texture and increased follicle density. PMID- 2227088 TI - Tretinoin therapy: practical aspects of evaluation and treatment. AB - Tretinoin has previously been used for the treatment of acne. Recent studies, however, demonstrating the efficacy of topical tretinoin in the treatment of photodamaged skin have led to its widespread use for this entirely new indication. When prescribing tretinoin for photodamaged skin rather than acne, physicians must take into consideration a new set of issues. Patients must be selected based on their commitment to a total sun-avoidance regimen. Evaluation of photodamage must be careful and thorough prior to initiating topical tretinoin therapy. Global assessment of a patient's photodamaged skin should be made before therapy and at all follow-up visits. The patient population treated for photodamage tends to be older than that using topical tretinoin for acne; therefore, the treatment regimen must account for the different clinical and physiological characteristics of older patients' skin. PMID- 2227089 TI - The effects of ultraviolet exposure on skin melanin pigmentation. AB - The main clinical, histological, ultrastructural and biochemical changes to the pigmentary system following photo-exposure are reviewed. Acute exposure to ultraviolet (UV) radiation induces an immediate pigment-darkening reaction, due to photo-oxidation of preformed melanin, followed by delayed tanning, the mechanism of which is unknown. Chronic exposure to UV induces photo-ageing with uneven pigment distribution. The most common pigmented lesions on chronically sun exposed skin include ephelides, solar lentigines and pigmented solar keratoses. Idiopathic guttate hypomelanosis is also common in sun-exposed skin and may be considered as a manifestation of photo-ageing. Chronic UV also appears to induce cutaneous melanomas. Psolaren UVA lentigines and sunbed lentigines provide good arguments for the fact that UV exposure can induce melanocyte dysplasia. In addition, various tumours involving the keratinocyte population are associated with increased pigmentation, suggesting a concomitant alteration in melanocyte function, as in the case of pigmented epitheliomas and pigmented actinic keratoses. The exact nature of the interactions between photo-exposure and melanocytes has yet to be fully established. PMID- 2227090 TI - A dual function of the Notch gene in Drosophila sensillum development. AB - We have investigated the function of the neurogenic gene Notch (N) during development of the adult sensilla of Drosophila. Heat pulses were applied to flies carrying the temperature-sensitive Notch allele Nts1 at different larval and pupal stages. We can show that the reduction of Notch+ function during a short interval prior to the onset of sensillum precursor division, resulting from a heat pulse between 0 and 14 hr after puparium formation (apf), leads to an increase in microchaete precursors at the expense of epidermal cells. The structure and cellular composition of the sensilla produced by these supernumerary precursors are normal. Later heat pulses which include the interval immediately after sensillum precursor division (14-20 hr apf) lead, among the progeny of the sensillum precursors, to a hyperplasia of sensory neurons, at the expense of accessory cells. The resulting "sensilla" consist of neurons only and lack the external cuticular structures (i.e., shaft, socket). These results demonstrate that similar mechanisms both of which involve the function of the Notch gene may be operating to sort out (premitotic) sensillum precursors from epidermal precursors and (postmitotic) sensory neurons from accessory cells. They further show that in postmitotic sensillum cells the differentiative fate is not yet irreversibly fixed, but presumably requires cell-cell interaction to become established. PMID- 2227091 TI - Adult expression of the Drosophila Lsp-2 gene. AB - Previous work has demonstrated expression of the larval serum protein-2 gene, Lsp 2, uniquely during the late larval and pupal stages of development in Drosophila melanogaster. Here we report that the LSP-2 polypeptide accumulates in the hemolymph throughout adult life as well. Western blot analysis using an LSP-2 antiserum reveals notable differences in the molecular weight of the larval and adult polypeptides. Lsp-2 transcription results in a unique mRNA of 2.3 kb, exhibiting the same 5' end in both larvae and adults. However, adult Lsp-2 mRNa is only expressed at 1% of the high level detectable in late third-instar larvae. Whereas Lsp-2 mRNA accumulates uniformly in all fat body cells of third-instar larvae, over 80% of the adult Lsp-2 transcript is expressed in the adipose tissue of the head. These results suggest a differential regulation for expression of the Drosophila Lsp-2 gene in adults and larvae. PMID- 2227092 TI - Mesodermal cell migration during Xenopus gastrulation. AB - The adhesive glycoprotein fibronectin (FN), which is a component of the network of extracellular matrix fibrils on the inner surface of the blastocoel roof (BCR), has been proposed to play a major role in directing mesodermal cell migration during amphibian gastrulation. In the first part of this paper, the adhesion of Xenopus mesodermal cells to FN in vitro is examined. Cells from several mesoderm regions, which differ in developmental fate and morphogenetic activity, are able to bind specifically to the RGD cell-binding site of FN. Dorsal mesodermal cell adhesion to FN varies along the anterior-posterior (a-p) axis: adhesion is strongest in the anterior head mesoderm, and gradually decreases posteriorly. This a-p gradient of mesodermal adhesiveness to FN does not change during mesodermal involution, and is reflected in the morphology of mesodermal explants on FN. An a-p strip of mesoderm develops a spreading, leading anterior margin and a compact, retracting posterior end, thus moving slowly and directionally over the FN substrate at about 0.8 micron/min. Although dissociated cells from all levels of the dorsal mesodermal axis adhere to FN, only the anterior, leading prospective head mesoderm cells migrate as single cells on a FN substrate in vitro. Locomotion by means of lamelliform protrusions occurs at an average rate of about 1.5 micron/min. Cells of the more posterior axial mesoderm merely shift position at random without substantial net translocation, and preinvolution mesoderm cells are completely stationary. On the BCR, the in vivo substrate for mesodermal cell migration, dissociated prospective head mesoderm cells spread and migrate as on FN in vitro, at 2.2 microns/min. In the presence of an RGD peptide which inhibits cell-FN interaction, cells remain globular and do not spread. They are still motile, but change direction frequently, which leads to less efficient net translocation. Apparently, interaction with the RGD cell-binding site of FN and concomitant spreading of head mesoderm cells is required for the stabilization of cell locomotion. In contrast to the directional migration of the mesoderm cell population toward the animal pole in the embryo, the pathways of dissociated cells on the BCR are randomly oriented. Coherent explants of migratory mesoderm do not move at all on the BCR, although they translocate on FN in vitro.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2227093 TI - Identification and developmental expression of a chicken calsequestrin homolog. AB - Calsequestrin (CAL) is a calcium-binding protein whose primary function is thought to involve sequestration of calcium in the muscle sarcoplasmic reticulum (SR). Little is known about the mechanisms regulating CAL expression, or about the role of this protein in muscle development. In addition, CAL may regulate calcium localization in some nonmuscle cells. We have identified an avian calsequestrin homolog. The predicted amino acid sequence of the avian CAL, first described as a laminin binding protein, and named aspartactin, is 70-80% identical to mammalian CAL sequences. We have used affinity-purified antibodies and cDNA probes to investigate expression in developing and adult chicken tissues. In adult chickens, the avian CAL homolog was expressed in slow and fast twitch skeletal muscle as well as in cardiac muscle. Surprisingly high levels of CAL protein were also detected in cerebellum. During development, CAL mRNA and protein were detected in Embryonic Day 5 (E-5) limb primordia, well before the initiation of myoblast fusion. In leg skeletal muscle, CAL protein and mRNA increase approximately 10-fold from E-8 to E-18 with a time course that just precedes myoblast fusion. This early expression pattern was also observed in cultured chicken pectoral myoblasts, and appears to be regulated at the level of mRNA abundance. The developmental profile of CAL expression is compared to that of other muscle proteins and possible additional functions of CAL are discussed. PMID- 2227094 TI - Transport of cationic and zwitterionic amino acids in preimplantation rat conceptuses. AB - The ability of preimplantation rat conceptuses to take up several amino acids was examined under a variety of conditions, and the characteristics of uptake were compared to those determined previously for mouse conceptuses. Mediated leucine transport in two-cell rat conceptuses is Na(+)-independent and inhibited almost completely by 2-amino-endobicyclo[2.2.1]heptane-2-carboxylic acid (BCH), so it resembles system L which predominates in two-cell mouse conceptuses. System L becomes less conspicuous than homoarginine-sensitive, Na(+)-independent leucine transport (provisionally designated system bo,+) by the time rat conceptuses develop into blastocysts, as is also the case for mouse conceptuses. In contrast to leucine transport, system bo,+ appears to be the most conspicuous transporter of cationic amino acids throughout preimplantation development of both species. A Na(+)-independent cation-preferring amino acid transport process also appears to be present in rat as well as in mouse conceptuses. Moreover, rat conceptuses resemble mouse conceptuses because Na(+)-dependent transport system Gly activity virtually disappears from them by the time they form blastocysts. Unlike mouse conceptuses, however, Na(+)-dependent system Bo,+ activity appears to be present throughout preimplantation development of rat conceptuses, whereas it has not been detected until at least the two-cell stage in the mouse. Although system Bo,+ becomes more conspicuous in mouse than in rat conceptuses by the time they form blastocysts, system Bo,+ activity appears to increase when blastocysts of both species are removed from the uterus just prior to implantation. The latter observation is consistent with the possibility that system Bo,+ activity is controlled, in part, by the uterus near the time of implantation, although further studies are needed to verify this possibility. Similarities as well as differences in the amino acid transport processes present in conceptuses of rats and mice may eventually be understood best in relation to the environments in which they develop in vitro and in situ. PMID- 2227095 TI - Developmental profiles of gangliosides in trisomy 19 mice. AB - The ganglioside composition of the cerebrum, cerebellum, brainstem, liver, heart, and spleen was analyzed quantitatively in trisomy 19 (Ts19) mice aged 4 to 12 days postpartum. The developmental profiles of cerebral gangliosides were similar in Ts19 mice and control littermates: Total ganglioside-sialic acid as well as the proportions of the individual gangliosides GD1a and GM1 increased with age, while the percentages of GQ1b and GT1b decreased during development. Both the accretion of the total ganglioside content and the development of the individual ganglioside fractions were delayed by 2-3 days in the Ts19 telencephalon. Likewise, the shift from the b- to the a-pathway of ganglioside synthesis was retarded. Ganglioside development was equally delayed in the cerebellum and the brainstem of Ts19 mice. Since in Ts19 mice, morphogenesis of several brain regions is similarly delayed by 2 days, these results confirm the usefulness of gangliosides as biochemical markers for brain maturation. In contrast to brain gangliosides, the ganglioside composition of the Ts19 livers was clearly distinguished from that of control livers. Total ganglioside-bound sialic acid was increased by 35-50% in Ts19 livers. This elevation in ganglioside content not explicable by a simple delay in development was mainly due to an increase in GD3 and fraction 2, which is likely to contain GD1a and GD1b. In contrast, GM2 which increased considerably with age in control mice persisted on a low level in Ts19 livers. Comparable alterations of the ganglioside pattern were neither observed in the spleen nor in the heart of Ts19 mice. The data presented give additional evidence that ganglioside synthesis in the liver is under a different regulation mechanism than that in the brain, heart, and spleen. PMID- 2227096 TI - Mutations in the par genes of Caenorhabditis elegans affect cytoplasmic reorganization during the first cell cycle. AB - A dramatic reorganization of cytoplasm occurs during the first cell cycle in embryos of the nematode, Caenorhabditis elegans. We present here the results of a quantitative study of some of the events during this reorganization in wild-type embryos and in par mutant embryos. The par mutations define a set of genes required for cytoplasmic localization in early embryos. We show that par mutations lead to defects in several events of the reorganization. Mutations in all four of the par genes we studied lead to defects in pseudocleavage and asymmetric redistribution of cortical microfilaments. In addition, some of the par mutations affect streaming of cytoplasm, migration of the pronuclei, and asymmetric shortening of the embryo. We propose that the major function of the par genes might be to orchestrate this initial reorganization of cytoplasm. PMID- 2227098 TI - Periodic calcium waves cross ascidian eggs after fertilization. AB - Ascidian eggs respond to fertilization with one to two dozen periodic calcium pulses (J.E. Speksnijder, D.W. Corson, C. Sardet, and L.F. Jaffe, 1989a, Dev. Biol. 135, 182-190). We examined the spatial pattern of these pulses and found that they are initiated in discrete regions from which they propagate as waves. The first few pulses start in the animal hemisphere, whereas the later ones are mostly initiated near the vegetal pole. Such vegetal waves are often followed by a contraction of the egg surface. Since these waves are attenuated as they spread, they repeatedly expose the vegetal pole region to more calcium. The mechanism of these repetitive calcium waves and their possible role in establishing pattern or completing meiosis is discussed. PMID- 2227097 TI - Protein kinase C activates the respiratory burst of fertilization, but not cortical granule exocytosis, in ionophore-stimulated sea urchin eggs. AB - In a "respiratory burst", fertilized sea urchin eggs consume oxygen to produce H2O2 as an extracellular oxidant to crosslink their protective surface envelopes. The egg generates H2O2 via a NADPH-specific oxidase that requires protein kinase C for activation. To further study the physiological regulation of the respiratory burst and cortical granule exocytosis, we have measured azide insensitive oxygen uptake and fertilization envelope assembly in ionophore stimulated eggs. Procaine, trifluoperazine, staurosporine, and H-7, which inhibit protein kinase C by different mechanisms, suppressed egg oxygen consumption without affecting fertilization envelope assembly. In contrast, both exocytosis and oxygen uptake were blocked in N-ethylmaleimide-treated eggs. When the eggs were stimulated with ionophore in Na-free artificial seawater, which prevents the increase in pHi, oxidase activity was inhibited. This effect was reversed by elevation of cytoplasmic pH with the membrane-permeant base NH4Cl. We conclude that protein kinase C was not involved in the events downstream from the ionophore-dependent elevation of Ca2+ which induced cortical granule exocytosis. However, the respiratory burst was inhibited despite the increase in Ca2+ that triggered exocytosis. The likely target for inhibition of the burst was protein kinase C. Cytoplasmic alkalinization was necessary for optimal rates of H2O2 synthesis, further implicating pHi as a regulator of the egg oxidase. PMID- 2227099 TI - Junctional acetylcholine receptor channel open time is not presynaptically regulated in developing muscle. AB - The role of motor innervation in controlling the development of acetylcholine receptor (AChR) channel open time was tested by examining synaptic current durations in transplanted muscles of Xenopus tadpoles. The presumptive lower jaw region, which gives rise to the interhyoideus muscle, was transplanted to the tail, overlying the myotomal muscle cells. The transplanted muscles became innervated, presumably by spinal nerves which normally innervate myotomal muscle. Despite development in the presence of foreign innervation, synaptic currents in the transplanted interhyoideus were predominantly long in duration and resembled those in the normally innervated interhyoideus. They did not resemble those in the myotomal muscle, where synaptic currents are brief. The apparent lack of neural influence on development of AChR function in muscle contrasts with the evidence for presynaptic control of AChR open time in frog sympathetic ganglia. This may reflect a fundamental difference between nerve and muscle in the regulation of postsynaptic function. PMID- 2227100 TI - Locale and level of bindin mRNA in maturing testis of the sea urchin, Strongylocentrotus purpuratus. AB - This first study of the onset of spermatogenesis in the sea urchin, Strongylocentrotus purpuratus, was undertaken using individuals reared in the laboratory. Spermatogenesis commences about 11-12 months after metamorphosis in these animals. Bindin message accumulates in late spermatocytes and early spermatids which lie in the luminal germinal layer. Bindin message accumulates later than does the testis-specific histone, H2b-1, suggesting that different classes of genes are sequentially activated during the differentiation of sperm. We correlate the number of bindin mRNA molecules with morphological structure and with quantitative aspects of gonad maturation including the number of nuclei and of sperm. The results suggest that the bindin mRNA concentration in total RNA from testis at different stages of maturation reflects the change in the proportion of expressing cells in the total cell population of the testis. PMID- 2227101 TI - Rapid induction of acetylcholine receptor aggregates by a neural factor and extracellular Ca2+. AB - A soluble fetal brain extract (EBX) induces acetylcholine receptor (AChR) aggregation in cultured rat myotubes within 4 hr at 36 degrees C in a defined medium containing 1.8 mM (normal) extracellular Ca2+ (Olek et al., 1983). The activity of EBX was Ca2+ dependent; reducing extracellular Ca2+ significantly inhibited EBX-induced AChR aggregation and a 15-50% increase in extracellular Ca2+ synergistically enhanced the activity of EBX. Synergism was specific for Ca2+ as increases in other divalent cations (Ba2+, Co2+, Mg2+, Mn2+, Sr2+) had no effect. A large increase (300-500%) in extracellular Ca2+ alone also induced AChR aggregation within 4 hr at 36 degrees C. An equivalent increase in other cations (Ba2+, Co2+, Mg2+, Mn2+, Sr2+) did not promote AChR aggregation. An initial 15 min pulse of increased extracellular Ca2+ alone or with EBX was adequate to induce AChR aggregation. Aggregates induced by EBX, Ca2+ alone, or EBX/Ca2+ were found predominantly on the top surface of the myotube. These treatments did not detectably alter preexisting aggregates present at substrate contact sites on the bottom surface of myotubes. AChR aggregation induced by any treatment was not inhibited by cycloheximide, Ca2+ channel blockers, or protease inhibitors but was blocked by Co2+ and sodium azide. PMID- 2227102 TI - The cortical cytoskeleton and its role in sperm penetration of the mammalian egg. AB - In this study isolated cortical regions of both penetrated and nonpenetrated Syrian hamster eggs were examined in whole mounts and platinum replicas of detergent-extracted cortical patches. Two types of cytoskeletal organization were observed in the egg cortex: Loose networks (LN regions) with integrated localized dense networks (LDN regions). Decoration with heavy meromyosin and labeling with antiactin/protein G gold both indicate that the cortical cytoskeleton consists mainly of a LN of actin microfilaments and several types of nonactin filaments, whereas LDN regions dispersed within the LN were comprised of nonactin filaments. Cortical patches and replicas of eggs incubated with sperm for 10-15 min provide evidence that cortical microfilaments may be intimately associated with penetrating spermatozoa. The results of this investigation provide the first high resolution view of the cortical cytoskeletal domain of a mammalian egg and suggest that actin microfilaments might play a role in sperm penetration of the egg cortex. PMID- 2227103 TI - Epidermal growth factor binding and receptor distribution in the mouse reproductive tract during development. AB - The ontogeny of the epidermal growth factor (EGF) receptor in the different cell types in the neonatal and immature mouse uterus and vagina was examined. Immunohistochemical examination of prenatal and neonatal reproductive tracts with a polyclonal antibody to the EGF receptor shows immunoreactive EGF receptors as early as Day 13 of gestation. Autoradiographic analysis of tissue sections at 3 to 17 days of age (the day of birth is Day 1) demonstrates that both uterine and vaginal epithelial and stromal cells are capable of binding 125I-labeled EGF. Both the 125I-labeled EGF autoradiography and immunohistochemistry in whole tissue show higher EGF receptor levels in the uterine epithelium than the uterine stroma. The presence of EGF receptors was also confirmed by affinity labeling and Scatchard analysis of isolated uterine cell types at 7 and/or 17 days of age. However, in contrast to the autoradiography and immunohistochemistry data of intact tissue, the affinity labeling and Scatchard data of isolated cells indicate that the uterine stroma contains higher levels of EGF receptor than that of the uterine epithelium. The reason for this discrepancy between the different techniques is, as yet, unknown. Regardless of the differences in the actual numbers of EGF receptors obtained, our data demonstrate that the developing mouse reproductive tract contains immunoreactive EGF receptors that are capable of binding 125I-labeled EGF. PMID- 2227104 TI - Target recognition by the archenteron during sea urchin gastrulation. AB - During sea urchin gastrulation filopodia are sent out by secondary mesenchyme cells (SMCs) at the tip of the archenteron in continual cycles of extension, attachment, and retraction. Eventually the archenteron ceases its elongation and its tip localizes to the animal pole region of the embryo (Gustafson and Kinnander, 1956, Exp. Cell Res. 11, 36-57; Dan and Okazaki, 1956, Biol. Bull. 110, 29-42). We have investigated the mechanisms and specificity of this localization by analyzing filopodial behavior and by experimental manipulation of the interaction of the archenteron with the animal pole region. When the tip of the archenteron nears the animal pole, some filopodia make contact with a well defined locus within this region. Filopodia that make contact with the locus remain attached 20-50 times longer than attachments observed at any other site along the blastocoel wall. The SMCs bearing the long-lived filopodia eventually change their phenotype by flattening and spreading onto this region. Several lines of experimental evidence indicate that contact with the animal pole locus, or "target" region, is crucial for the change in phenotype of the SMCs: (1) the phenotypic change can be induced precociously by bringing the animal pole region within reach of the tip of the archenteron early in gastrulation. Precocious contact with other regions of the blastocoel wall does not induce a similar change. (2) The phenotypic change can be delayed by placing the animal pole out of reach late in gastrulation, resulting in artificial prolongation of exploratory behavior by filopodia. (3) Ectopic combinations of animal pole ectoderm and archenterons in fused multiple embryos and chimaeras result in attachment of archenterons to the nearest available target, and (4) freely migrating SMCs are observed to migrate randomly within the blastocoel, then stop at the animal pole and undergo the change in phenotype. Filopodia rapidly attach to the animal pole when the shape of early gastrulae is altered such that the animal pole is less than 35 microns from the tip of the archenteron, even though such attachments only occur in normal embryos at the 2/3-3/4 gastrula stage. Since it has previously been shown that the archenteron elongates autonomously to 2/3 of its final length (Hardin, 1988, Development 103, 317-324), it appears that autonomous extension of the archenteron is required to place filopodia close enough to the animal pole to allow them to interact with it.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2227105 TI - Mapping genes in diabetes. Genetic epidemiological perspective. AB - Research on mapping diabetes-susceptibility genes is dependent on several factors, including the existence of a single major gene for susceptibility, genetic homogeneity, and the existence of appropriate clinical material. The power to detect susceptibility genes is dependent on the risks in relatives and the distance of genetic markers from the susceptibility genes. For insulin dependent diabetes mellitus (IDDM), the best-fitting risk models are those with a single major locus with residual polygenic factors. The major locus effect is likely represented by genes in the HLA complex, because specific genotypes have been found to affect IDDM risk significantly. Thus, mapping the remaining polygenic IDDM susceptibility factors--each of small effect--is a difficult and long task. For non-insulin-dependent diabetes mellitus (NIDDM), the likely risk models result in few genes with moderate effect. Models of NIDDM have significant residual polygenic variation remaining, reflecting the importance of multiple loci with small effect, environmental effects, or genetic heterogeneity; however, the prospects for mapping genes that provide at least moderate susceptibility for NIDDM now appear promising. PMID- 2227106 TI - Marked improvement of glucose homeostasis in diabetic ob/ob mice given oral vanadate. AB - The trace element vanadium exerts insulinlike effects in vitro and decreases hyperglycemia in insulin-deficient animals. This study examined whether vanadate can improve glucose homeostasis in genetically obese hyperglycemic insulin resistant ob/ob mice, which present metabolic abnormalities similar to those of human non-insulin-dependent diabetes. Sodium orthovanadate (0.3 mg/ml) was administered for 7 wk in H2O. Vanadate treatment induced a fall in fed and fasted plasma glucose and insulin levels and improved tolerance to oral glucose; the stimulated glucose area was decreased by 65%, and an early peak of insulin secretion was restored. During an intravenous glucose tolerance test, the glucose disappearance rate was twofold higher in vanadate-treated mice, and the reappearance of a significant insulin response was also observed. Moreover, vanadate produced a twofold increase in hepatic glycogen content and prevented the exhaustion of pancreatic insulin stores. The hypoglycemic response to exogenous insulin was similar in control and treated mice. In vitro experiments showed that basal glucose oxidation by hemidiaphragms was 32% higher in vanadate treated mice than in controls, although stimulation by insulin was similar in both groups. In conclusion, oral vanadate caused a marked and sustained improvement of glucose homeostasis in diabetic insulin-resistant mice by exerting an insulinlike effect on peripheral tissues and apparently preventing the exhaustion of pancreatic insulin stores. PMID- 2227107 TI - Short-term administration of captopril and nifedipine and exercise-induced albuminuria in normotensive diabetic patients with early-stage nephropathy. AB - Recent studies have demonstrated that short-term angiotensin converting enzyme (ACE) inhibition with captopril can reduce urinary albumin excretion rate (UAER) after exercise in normotensive diabetic patients with early-stage nephropathy. The aim of this study was to investigate whether this effect of ACE inhibition was due to a systemic hypotensive action or a specific action at the intrarenal level. Thus, we compared the acute effects of captopril and the Ca2(+)-channel blocker nifedipine on exercise-induced UAER in normotensive (blood pressure less than 165/95 mmHg) diabetic patients who were normoalbuminuric or microalbuminuric at rest (stage 2 or 3 of diabetic nephropathy). Twenty-five stage 2 diabetic nephropathy patients, 39 stage 3 diabetic nephropathy patients, and 12 nondiabetic subjects performed five submaximal cycloergometric exercises (90% of theoretical heart rate) on nonconsecutive days. The first two exercises were performed in basal conditions; the next three exercises were performed 24 h after administration of captopril (25 mg twice daily) or nifedipine AR (20 mg twice daily) or placebo (1 tablet twice daily) according to a randomized double-blind crossover trial. After placebo, blood pressure and UAER did not change at rest or 1 h after exercise. After captopril, blood pressure at rest and during exercise was similar to that observed after placebo. UAER at rest was not modified, whereas 1 h after exercise, it was significantly decreased both in stage 2 and stage 3 diabetic nephropathy patients (P less than 0.001). After nifedipine, blood pressure decreased significantly at rest and during exercise in respect to placebo and captopril. UAER at rest did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227108 TI - Effect of bacitracin on retroendocytosis and degradation of insulin in cultured kidney epithelial cell line. AB - In an earlier study, we described the presence of a retroendocytotic pathway for insulin in a cultured kidney epithelial cell line. Derived from the opossum kidney (OK), these cells possess many features of proximal tubule epithelium, which is the major site of kidney insulin metabolism. We studied the interaction between the retroendocytotic and the degradative pathways with bacitracin as a pharmacological probe. Monolayers of OK cells were loaded with 125I-labeled insulin over 30 min, acid washed to remove membrane-bound insulin, then incubated in fresh medium for 60 min while the release of intracellular radioactivity was monitored. In experiments carried out in the presence of bacitracin (2 mM), there was a two-thirds increase in intracellular radioactivity at the end of the loading phase. Measurements made during the subsequent release phase showed that bacitracin reduced the release of degradation products. Thus, although controls released 72.1 +/- 8.1% of the internalized radioactivity as trichloroacetic acid (TCA)-soluble products, bacitracin-treated cells released 59.2 +/- 9.4% (P less than 0.02). In contrast, release of TCA-precipitable insulin increased from 15.2 +/- 4.6% in controls to 25.8 +/- 3.7% in bacitracin-treated cells (P less than 0.01). In separate experiments analyzed by gel-exclusion chromatography, 6.4 +/- 0.6% of radioactivity released from preloaded control cells into medium over 60 min was insulin sized compared to 29.7 +/- 1.4% in bacitracin-treated cells. High performance liquid chromatography revealed that 61.5 +/- 3.5% of this insulin sized material released from control cells preloaded with A14-insulin eluted as intact insulin and the remainder as unidentified intermediate degradation products.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227109 TI - Abnormal redox status without increased lipid peroxidation in sugar cataract. AB - In conflict with a previous report, we find that phenolic inhibitors of lipid peroxidation (butylated hydroxytoluene [BHT] and butylated hydroxyanisole [BHA]) do not have significant inhibitory effect on galactosemic cataract formation. This is consistent with the lack of enhancement of stable products of lipid peroxidation (measured by the thiobarbituric acid assay) in the lenses of galactosemic rats. This does not imply that oxidative stress plays no role in galactosemic cataract formation (indeed, we find that galactosemic lens homogenates contain increased amounts of an Fe2+ oxidant, possibly a peroxide), but rather that BHT- and BHA-inhibitable lipid peroxidation specifically has no role to play. In instances where drugs appear to inhibit galactosemic cataract formation, other effects caused by the drugs, e.g., inhibition of feeding or induction of general detoxification pathways, must be considered. PMID- 2227110 TI - Determination of portal insulin absorption from peritoneum via novel nonisotopic method. AB - The absorption mechanism of insulin administered in the peritoneal cavity (IP) is of current interest because of the near availability of implantable insulin infusion devices for the treatment of diabetes. To determine the fraction of insulin absorbed by the portal circulation after IP administration, a novel nonisotopic method is described. Conscious fasting diabetic dogs were studied at normoglycemia via the euglycemic insulin-clamp method. Posthepatic appearance of insulin and C-peptide were measured in peripheral blood during IP or intravenous (IV) equimolar infusion of insulin and C-peptide at two sequential 3-h infusion rates of 3.2 and 12.8 pmol.kg-1.min-1. Prior studies have shown that 40-60% of portal insulin is extracted at first pass by the liver, whereas C-peptide is not extracted. Thus, the fraction (F) of IP insulin not taken up by liver at first pass and consequently the fraction absorbed by the portal circulation can be derived from insulin (I) and C-peptide (C) plasma concentration values at steady state with a monocompartmental model where F = (IIP/IIV)(CIV/CIP). The mean +/- SE value of F was 49.7 +/- 8.8%. Glucose disappearance rates were lower with IP than IV infusion but similar when peripheral insulin levels were matched. We conclude that IP insulin is almost entirely absorbed by the portal circulation and induces lower glucose disappearance rates than IV insulin because of lower peripheral circulating insulin levels. Whether these properties make the IP route a more appropriate route for insulin therapy than the subcutaneous or IV routes remains to be established. PMID- 2227111 TI - Anti-islet cell antibodies from NOD mice. AB - We produced a panel of monoclonal autoantibodies from the spleen cells of prediabetic nonobese diabetic mice. The antibodies were selected on the basis of their ability to bind to the surface of nondiabetic mouse islet cells, and from greater than 4000 hybridomas screened, 35 islet-reactive antibodies were isolated. Most of these reagents also bind to nondiabetic rat and human islet cells and beta-cell tumor lines. A few of the antibodies were found to be reactive with insulin. When tested for cross-reactivity with other cell types, most of the antibodies were found to be islet specific. PMID- 2227112 TI - Inhibition of hepatic glucose production by SDZ 51641. AB - The new oral hypoglycemic agent SDZ 51641 was evaluated in nondiabetic rats and a rat model of human non-insulin-dependent diabetes mellitus. Diabetes was induced with a single injection of 37.5 mg/kg streptozocin, and the rats exhibited hyperglycemia in the fed state with normal insulin levels. Treatment of nondiabetic animals with 100 mg/kg SDZ 51641 given orally significantly decreased serum glucose and ketone levels within 4 h without affecting insulin levels. Nonesterified fatty acids increased more than twofold during the same period. Its effect on ketone and fatty acid levels suggests that SDZ 51641 acts as an inhibitor of fatty acid oxidation. Diabetic rats treated with SDZ 51641 exhibited a significant acute hypoglycemic response, which was more pronounced after 3 days of treatment. The compound also significantly decreased serum cholesterol and triglyceride levels 27 and 53%, respectively. When endogenous hepatic glucose production was assessed in nondiabetic and diabetic animals via continuous infusion of [3-3H]glucose, we found that hepatic glucose production was elevated 43% in diabetic compared with control animals. When diabetic rats were treated with 100 mg/kg SDZ 51641, hepatic glucose production decreased to normal levels within 6 h. Hyperinsulinemic-euglycemic clamp studies indicated that SDZ 51641 had no effect on insulin-stimulated glucose utilization. Measurement of [1 14C]oleate oxidation in isolated hepatocytes demonstrated that SDZ 51641 inhibited long-chain fatty acid oxidation in a concentration-dependent manner. The compound was ineffective at inhibiting long-chain fatty acid oxidation in epitrochlearis or soleus muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227113 TI - Insulinlike activity of new antidiabetic agent CP 68722 in 3T3-L1 adipocytes. AB - We examined the in vitro effects of CP 68722, a novel antidiabetic agent, in 3T3 L1 adipocytes. CP 68722 stimulated 2-deoxyglucose uptake in the absence of insulin. At least 30 min of incubation were required for stimulation of uptake. This effect increased over 5 h and was sustained up to 72 h. The stimulation of 2 deoxyglucose uptake by CP 68722 could be inhibited approximately 60% by inhibition of protein synthesis with cycloheximide. Half-maximal and maximal responses to CP 68722 at 72 h of incubation were observed at 10 and 100 microM of drug, respectively, with a threefold stimulation of uptake at 100 microM approximating the maximal response of these cells to acute insulin stimulation. CP 68722 was able to overcome insulin resistance induced by dexamethasone in 3T3 L1 cells. The effect of drug, like that of insulin, was primarily to increase the Vmax of 2-deoxyglucose uptake. The stimulation of uptake by CP 68722 or insulin could be prevented by incubating the cells at 10 degrees C, a temperature that impedes translocation of glucose transporters to the plasma membrane. Therefore, it appears that CP 68722, like insulin, stimulates glucose uptake by a mechanism that involves translocation of intracellular glucose transporters to the plasma membrane and de novo protein synthesis. We compared the effect of CP 68722 with the sulfonylureas, the primary drugs used in the treatment of non-insulin dependent diabetes mellitus (NIDDM). CP 68722 was a more potent and effective stimulator of 2-deoxyglucose uptake in 3T3-L1 cells than either first- or second generation sulfonylureas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227114 TI - Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. AB - It has been postulated that the etiology of the complications of diabetes involves oxidative stress, perhaps as a result of hyperglycemia. Consistent with this hypothesis, it has been shown that glucose, under physiological conditions, produces oxidants that possess reactivity similar to the hydroxyl free radical. These oxidants hydroxylate benzoic acid, fragment protein, and induce peroxidation in phosphatidylcholine liposomes and low-density lipoprotein (LDL) when LDL is incubated with hyperglycemic levels of glucose in vitro. These reactions are accelerated by transition metals and inhibited by a metal-chelating agent. The atherosclerotic potential of LDL in diabetes mellitus is often discussed in terms of protein glycosylation, which may affect cellular interactions. Our studies demonstrate, however, that peroxidative reactions also accompany LDL glycosylation in vitro. Peroxidative modification of LDL has also been implicated in LDL atherogenicity. Our studies indicate that glycosylation and peroxidation occur concomitantly in LDL modified by glucose in vitro and may both contribute to the behavioral changes of this lipoprotein. PMID- 2227115 TI - Effects of exercise training on insulin-regulatable glucose-transporter protein levels in rat skeletal muscle. AB - Exercise training has been shown to enhance the ability of insulin to stimulate glucose uptake in responsive tissues. The purpose of this study was to determine the effects of exercise training on the levels of the insulin-regulatable glucose transporter (IRGT) in rat skeletal muscle. After 6 wk of voluntary running in exercise-wheel cages, male Sprague-Dawley rats were rested for approximately 27 h and fasted overnight before removal of plantaris and soleus muscles. The concentration of glucose transporters per unit of muscle protein or DNA was quantitated by immunoblotting with an anti-IRGT polyclonal antibody raised against a synthetic peptide. The IRGT protein was increased by 60% (141 +/- 14 vs. 229 +/- 24 counts/min [cpm]/25 micrograms protein, P less than 0.01) in plantaris muscle from exercise-trained rats compared with controls. Total protein yield, DNA content, and 5'-nucleotidase activity were not different in plantaris muscle from control and exercise-trained rats. In contrast, there was no significant increase in the IRGT protein in soleus muscle after training when data were expressed per unit of muscle protein (292 +/- 22 vs. 346 +/- 16 cpm/25 micrograms protein). These data indicate that the increase in the IRGT in plantaris muscle is a selective response to exercise training that does not reflect an overall increase in muscle protein. The changes in IRGT for these muscles with exercise training parallel changes observed in insulin-mediated glucose uptake. We propose that this increase in the total number of glucose transporters may be a major component of the increase in insulin-mediated glucose uptake that is observed with exercise training. PMID- 2227116 TI - Insulin and hypertension. Relationship to obesity and glucose intolerance in Pima Indians. AB - The relationships among blood pressure, obesity, glucose tolerance, and serum insulin concentration were studied in 2873 Pima Indians aged 18-92 yr (mean 37 yr). Age- and sex-adjusted to the Pima population, the prevalence of hypertension (systolic blood pressure greater than or equal to 160 mmHg, diastolic blood pressure greater than or equal to 95 mmHg, or receiving drug treatment) was 7.1% for subjects with normal glucose tolerance compared with 13.0% for subjects with impaired glucose tolerance (IGT) and 19.8% for those with non-insulin-dependent diabetes mellitus (NIDDM) (P less than 0.001). The prevalence ratio of hypertension was 1.8 (95% confidence interval [CI] 1.2-2.5) for IGT and 2.6 (95% CI 2.0-3.2) for NIDDM compared with normal glucose tolerance, controlled for age, sex, and body mass index (BMI). In logistic regression analysis, hypertension was positively related to age, male sex, BMI, glucose tolerance, and fasting but not 2-h postload serum insulin concentration. Among subjects not taking antihypertensive drugs, however, neither fasting nor 2-h postload serum insulin was significantly related to hypertension. Furthermore, in 2033 subjects receiving neither antihypertensive nor antidiabetic drugs, blood pressure was not significantly correlated to fasting insulin concentration, and 2-h postload serum insulin was negatively correlated with diastolic blood pressure. In conclusion, insulin is not significantly related to blood pressure in Pima Indians not receiving antihypertensive drugs. Higher insulin concentrations in drug-treated hypertensive patients might result from the treatment rather than contribute to the pathogenesis of hypertension. Thus, these data do not support a major role for insulin in determining the occurrence of hypertension or regulation of blood pressure in Pima Indians. PMID- 2227117 TI - Structural abnormality in LDL from diabetic patients as revealed by resonance Raman spectroscopy. AB - Resonance Raman spectra of low-density lipoprotein (LDL) isolated from the plasma of diabetic patients (age range 13-77 yr, mean age 37 yr) and age- and sex matched control subjects were recorded in the 1000- to 1600-cm-1 region as a function of temperature (0-50 degrees C). Both nondiabetic and diabetic LDL yield spectra characterized by two major bands near 1160 and 1530 cm-1 due to the carotenoid component of lipoproteins. The relative intensity of 1530- and 1160-cm 1 bands, assigned to -C = C- and = C-C = stretchings, respectively, i.e., I1530 I1160 ratio, was plotted against temperature. For nondiabetic control subjects, the plots showed an inflection in the temperature range of 30-39 degrees C, which corresponded to the thermal transition of LDL. This transition was abolished in the LDL of diabetic patients (P less than 0.001), suggesting an altered lipid structure. The transition (30-39 degrees C) was also abolished in the in vitro glycosylated nondiabetic LDL. Lipid analysis did not show any appreciable change between nondiabetic control subjects and diabetic patients. The change in the thermal transition properties of diabetic LDL has been attributed to the organizational change in the LDL protein. PMID- 2227118 TI - Glucose-induced electrical activity in beta-cells. Feedback control of ATP sensitive K+ channels by Ca2+? [corrected]. AB - Glucose regulates Ca2+ influx in beta-cells by controlling a rhythmic electrical activity (slow waves with spikes). However, the glucose-sensitive feedback system that triggers repolarization at the end of the slow waves, and thus stops Ca2+ influx, is unknown. Raising extracellular Ca2+ to 10 mM shortened slow waves in mouse beta-cells perifused with medium containing 15 mM glucose and restored slow waves when persistent depolarization and continuous spike activity were induced by 30 mM glucose. The effects of high Ca2+ were reversed or prevented by tolbutamide, whereas 1 mM tetraethylammonium only increased spike amplitude. This suggests that a feedback action of Ca2+ on ATP-sensitive K+ channels rather than on voltage- and Ca2(+)-activated K+ channels may be involved in slow wave generation. Metabolic modulation of this feedback could be central in the regulation of electrical activity and, hence, insulin release. PMID- 2227119 TI - Human insulin-receptor gene. AB - The human insulin-receptor (hINSR) gene spans a region of greater than 120,000 base pairs (bp) on the short arm of chromosome 19. It is comprised of 22 exons or coding regions that vary in size from 36 to greater than 2500 bp. To a large degree, the introns appear to divide the hINSR gene into segments that encode structural and/or functional elements of the hINSR protein. The exon-intron organization of the hINSR gene provides a clue to the evolutionary history of this gene and suggests that it is a mosaic constructed from protein-coding regions recruited from other genes. Eight mutations in the hINSR gene that result in expression of structurally abnormal proteins have been described. These mutations are associated with insulin resistance and provide insight into the role of the hINSR gene in the development of diabetes mellitus. PMID- 2227120 TI - Defective free-fatty acid and oxidative glucose metabolism in IDDM during hypoglycemia. Influence of glycemic control. AB - To examine the impact of diabetes and its treatment on plasma free-fatty acid (FFA) and oxidative fuel metabolism during hypoglycemia, we combined indirect calorimetry with [3-3H]glucose during a 4-h low-dose insulin infusion (plasma insulin approximately 2-fold above basal) in six poorly controlled and nine well controlled insulin-dependent diabetes mellitus (IDDM) patients and in six healthy subjects. Diabetic subjects received insulin overnight to maintain euglycemia before study. Although free-insulin levels and counterregulatory hormone responses were similar, the plasma glucose fall was more pronounced in well controlled diabetic subjects. In well-controlled diabetic and healthy subjects, the small increment in insulin rapidly suppressed plasma FFA and fat oxidation by approximately 50% and stimulated carbohydrate oxidation by approximately 80%. In contrast, plasma FFA levels did not fall in poorly controlled diabetic subjects, and glucose oxidation was not stimulated. To determine whether this resistance to the antilipolytic effect of insulin occurs in the absence of hypoglycemic counterregulation, we used a sequential low-dose euglycemic insulin clamp (0.2, 0.3, and 0.5 mU.kg-1.min-1). In healthy subjects, plasma FFA was nearly maximally suppressed at the lowest insulin dose. In contrast, plasma FFA remained persistently elevated in poorly controlled diabetic subjects at each insulin dose. However, the insulin dose-response curve for suppression of plasma FFA was near normal in well-controlled subjects. We conclude that poorly controlled IDDM diabetic patients are resistant to the antilipolytic effects of insulin and show impaired stimulation of glucose oxidation during insulin-induced hypoglycemia. Amelioration of these defects in well-controlled patients may be another factor contributing to the higher risk of hypoglycemia during intensified insulin therapy. PMID- 2227121 TI - Pattern of postprandial carbohydrate metabolism and effects of portal and peripheral insulin delivery. AB - The importance of portal insulin delivery in the regulation of postprandial carbohydrate metabolism is uncertain. To address this question, three groups of dogs were studied: one group in which pancreatic venous drainage was transected and reanastomosed (portal insulin delivery), one in which the pancreatic drainage was transected and anastomosed to the inferior vena cava (peripheral insulin delivery), and one that received only a sham operation. Plasma insulin was greater (P less than 0.05) during peripheral insulin delivery than in either the portal or sham groups, respectively, before and after meal ingestion. On the other hand, C-peptide concentrations did not differ between groups, resulting in a higher (P less than 0.001) insulin to C-peptide ratio in the peripheral group. This indicated that the hyperinsulinemia in the peripheral group was due to decreased insulin clearance rather than increased insulin secretion. Isotopically determined splanchnic uptake of ingested glucose, postprandial suppression of hepatic glucose release, incorporation of CO2 into glucose (a qualitative measure of gluconeogenesis), and total-body glucose uptake were virtually identical in all groups. Similarly, plasma lipid, beta-hydroxybutyrate, and lactate concentrations did not differ between groups. Our data indicate that, despite differences in systemic insulin concentration, portal and peripheral insulin delivery comparably regulate hepatic and extrahepatic carbohydrate metabolism after meal ingestion. PMID- 2227122 TI - Metabolic effects of hyperglycemia and hyperinsulinemia on fate of intracellular glucose in NIDDM. AB - Hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) stimulates peripheral glucose uptake, which tends to compensate for impaired insulin mediated glucose uptake. The metabolic fate of glucose and suppression of fat oxidation may differ, however, when glucose uptake is stimulated primarily by insulin or hyperglycemia. To address this issue, three hyperinsulinemic glucose clamp studies were performed in combination with indirect calorimetry in seven nonobese subjects with NIDDM. In the first two experiments, when glucose uptake was matched at approximately 8 mg.kg-1 fat-free mass (FFM).min-1 with primarily hyperinsulinemia (1350 +/- 445 pM) or hyperglycemia (20.8 +/- 1.8 mM), identical rates of glucose oxidation (3.21 +/- 0.29 and 3.10 +/- 0.23 mg.kg-1 FFM.min-1, NS) and nonoxidative glucose metabolism (5.19 +/- 0.75 and 5.46 +/- 0.61 mg.kg-1 FFM.min-1, NS) were achieved. When glucose uptake was increased further to 11.11 +/- 0.36 mg.kg-1 FFM.min-1 with less insulin (625 +/- 70 pM) and hyperglycemia, glucose oxidation (3.85 +/- 0.26 mg.kg-1 FFM.min-1) and nonoxidative glucose metabolism (7.26 +/- 0.51 mg.kg-1 FFM.min-1) rose significantly (both P less than 0.05 from matched studies at lower rates of glucose uptake). During all glucose clamp studies, free fatty acids were comparably suppressed by 40-46% (all P less than 0.005 vs. basal values), whereas fat oxidation was suppressed by 70-80% (all P less than 0.005 vs. basal values). A strong negative correlation was observed between rates of glucose and fat oxidation (r = -0.88, P less than 0.001) when all studies were combined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227123 TI - Calcitonin gene-related peptide and induction of hyperglycemia in conscious rats in vivo. AB - The effect of calcitonin gene-related peptide (CGRP) on glucose metabolism was investigated in conscious and unrestrained rats in vivo. Intravenous injection of rat CGRP (5.67 and 0.567 nmol/kg) caused a significant, dose-dependent increase in plasma glucose concentration and a simultaneous dose-dependent increase in plasma insulin level. In contrast, plasma glucagon level was not changed. On the other hand, intravenous infusion of CGRP (46.6 pmol.kg-1.min-1) decreased tolerance to intragastric administration of glucose (IGGTT). Plasma insulin response to IGGTT, however, was not affected by CGRP infusion. Moreover, although intravenous injection of CGRP (5.67 nmol/kg) elicited a significant increase in plasma epinephrine and norepinephrine concentrations, concomitant administration of epinephrine and norepinephrine, inducing a more prominent rise in plasma catecholamines than those induced by CGRP, affected neither plasma glucose nor insulin levels. Finally, plasma insulin levels obtained by simulating CGRP induced changes in plasma glucose or glucose plus catecholamine levels by infusion of glucose or glucose plus catecholamines were not different from those induced by CGRP injection. These results suggest that CGRP has a hyperglycemic action that is not mediated by sympathetic outflow in conscious rats, and inhibition of insulin secretion, if any, does not play a major role in this hyperglycemic action of CGRP. We have demonstrated specific CGRP receptors linked to adenylate cyclase activation in rat liver plasma membranes; this hyperglycemic effect of CGRP in vivo may be partly due to its direct action on the liver. PMID- 2227124 TI - Change in hexose distribution volume and fractional utilization of [18F]-2-deoxy 2-fluoro-D-glucose in brain during acute hypoglycemia in humans. AB - We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min 1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-min period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi [18F]-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/ 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/ 7 pM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227125 TI - Effects of insulin on diacylglycerol-protein kinase C signaling in rat diaphragm and soleus muscles and relationship to glucose transport. AB - Insulin was found to provoke rapid increases in diacylglycerol (DAG) content and [3H]glycerol incorporation into DAG and other lipids during incubations of rat hemidiaphragms and soleus muscles. Insulin also rapidly increased phosphatidic acid and total glycerolipid labeling by [3H]glycerol, suggesting that insulin increases DAG production at least partly through stimulation of the de novo pathway. Increased DAG production may activate protein kinase C (PKC) as reported previously in the rat diaphragm. We also observed apparent insulin-induced translocation of PKC from cytosol to membrane in the rat soleus muscle. The importance of insulin-induced increases in DAG-PKC signaling in the stimulation of glucose transport in rat diaphragm and soleus muscles was suggested by 1) PKC activators phorbol esters and phospholipase C stimulation of [3H]-2-deoxyglucose (DOG) uptake and 2) PKC inhibitors staurosporine and polymixin B inhibition of insulin effects on [3H]-2-DOG uptake. Although phorbol ester was much less effective than insulin in the diaphragm, phospholipase C provoked increases in [3H]-2-DOG uptake that equaled or exceeded those of insulin. In the soleus muscle, phorbol ester, like phospholipase C, was only slightly but not significantly less effective than insulin. Similar variability in effectiveness of phorbol ester has also been noted previously in rat adipocytes (weak) and BC3H1 myocytes (strong), whereas DAG, added exogenously or generated by phospholipase C treatment, stimulates glucose transport to a degree that is quantitatively more comparable to that of insulin in each of the four tissues. Differences in effectiveness of phorbol ester and DAG could not be readily explained by postulating that the latter acts independently of PKC, because DAG provoked the apparent translocation of the enzyme from cytosol to membranes in rat adipocytes, and effects of DAG on [3H]-2-DOG uptake were blocked by inhibitors of PKC in both rat adipocytes and BC3H1 myocytes. Collectively, our findings provide further support for the hypothesis that insulin increases DAG production and PKC activity, and these processes are important in the stimulation of glucose transport in rat skeletal muscle and other tissues. PMID- 2227126 TI - Is insulinlike growth factor I associated with diabetic retinopathy? AB - Insulinlike growth factor I (IGF-I) is the mediator of the growth-promoting effects of growth hormone and has been suspected of playing a role in the pathogenesis of proliferative diabetic retinopathy (PDR). However, previous attempts to correlate IGF-I levels with PDR have yielded conflicting results. We determined IGF-I levels in a large population-based study of 682 early-onset (diagnosed before 30 yr of age) adult (greater than or equal to 18 yr old) insulin-taking diabetic subjects. PDR was found in 25% of the population. IGF-I levels were measured by radioimmunoassay. The mean serum level of IGF-I was 277 +/- 108 micrograms/L (mean +/- SD). Spearman rank correlations showed statistically significant negative correlations between IGF-I levels and age (r = -0.51, P less than 0.0001), duration of disease (r = -0.36, P less than 0.0001), and glycosylated hemoglobin (r = -0.09, P less than 0.05). There was a significant trend (P less than 0.001) toward decreasing risk of PDR with increasing IGF-I. However, after controlling for duration of diabetes, glycosylated hemoglobin, diastolic blood pressure, and the presence of proteinuria and/or creatinine greater than or equal to 265 microM in a multiple logistic regression model, IGF-I was not significantly associated with PDR. These data suggest that IGF-I may not be a risk factor for the development of PDR. PMID- 2227127 TI - Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthase inhibition. AB - We examined steady-state levels of mRNA encoding type IV collagen, B1 chain of laminin, and the basement membrane heparan sulfate proteoglycan in the kidney cortex of a mouse model (KKAy) of non-insulin-dependent diabetes. mRNAs encoding laminin B1 and the proteoglycan were unchanged in kidneys taken from diabetic mice with demonstrable basement membrane thickening. mRNA levels for type IV collagen, in contrast, were significantly elevated (2-fold) in diabetic mice concurrent with but not preceding morphologically thickened basement membranes. There was a negative correlation between a ratio of proteoglycan/type IV collagen and levels of albuminuria in the diabetic mice. No correlation was noted with laminin. We also examined the effects of inhibiting the synthesis of thromboxane, a potent vasoconstrictor, on the steady-state levels of type IV collagen in the diabetic mice. Inhibition of thromboxane stopped the progression of albuminuria and prevented an increase in type IV collagen mRNA levels. We conclude that basement membrane thickening in diabetes, a hallmark of diabetic nephropathy, is partly a consequence of an unbalanced increase in the production of type IV collagen. The relative decrease in proteoglycan production may contribute to chronic albuminuria. PMID- 2227128 TI - Lack of predictive value of islet cell antibodies, insulin antibodies, and HLA-DR phenotype for remission in cyclosporin-treated IDDM patients. The Canadian European Randomized Control Trial Group. AB - The effect of immunosuppression on the humoral immune response to islet autoantigens and exogenously administered insulin and the predictive value of islet cell cytoplasmic antibodies (ICAs), insulin antibodies (IAs), and HLA-DR phenotype for remission during immunosuppression were studied in a prospective randomized double-blind trial of cyclosporin administration in 98 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients. HLA-DR phenotype and glycosylated hemoglobin were determined at study entry, and insulin requirement, glucagon-stimulated C-peptide, ICAs, and IAs were measured at entry and after 1, 3, 6, 9, and 12 mo of follow-up. Cyclosporin therapy caused significant suppression of the prevalence and serum concentrations of ICAs and IAs. Cyclosporin-treated IDDM patients ICA+ at study entry had higher levels of stimulated C-peptide after 1 mo of study, but the increased beta-cell function was not associated with a higher frequency of insulin-free remission at 1 mo. ICA and IA status at entry did not predict cyclosporin-insulin-free remission as assessed by the prevalence of insulin-free remission or beta-cell function at 3 12 mo of study, and significant decrements in the titers or total disappearance of ICAs were not associated with an increased prevalence or duration of non insulin-requiring remission or higher stimulated C-peptide values. There was no correlation between the serum levels of ICAs and IAs at entry and beta-cell function at 12 mo of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227129 TI - Contribution of impaired muscle glucose clearance to reduced postabsorptive systemic glucose clearance in NIDDM. AB - The reduced postabsorptive rates of systemic glucose clearance in non-insulin dependent diabetes mellitus (NIDDM) are thought to be the consequence of insulin resistance in peripheral tissues. Although the peripheral tissues involved have not been identified, it is generally assumed to be primarily muscle, the major site of insulin-mediated glucose disposal. To test this hypothesis, we measured postabsorptive systemic and forearm glucose utilization and clearance in 15 volunteers with NIDDM and 15 age- and weight-matched nondiabetic volunteers. Although systemic glucose utilization was increased in NIDDM subjects (14.5 +/- 0.5 vs. 11.2 +/- 0.2 mumol.kg-1.min-1, P less than 0.001), systemic glucose clearance was reduced 1.40 +/- 0.06 vs. 2.13 +/- 0.05 ml.kg-1.min-1, P less than 0.01). Although forearm glucose utilization was increased in NIDDM subjects (0.663 +/- 0.058 vs. 0.411 +/- 0.019 mumol.dl-1.min-1, P less than 0.001), forearm glucose dl-1 clearance was reduced (0.628 +/- 0.044 vs. 0.774 +/- 0.037 ml.L-1.min-1, P less than 0.01). However, extrapolation of forearm data to total body muscle indicated that impaired clearance reduced muscle glucose disposal by only 61 +/- 21 mumol/min, whereas impaired systemic clearance reduced systemic glucose disposal by 662 +/- 82 mumol/min. Thus, impaired muscle glucose clearance accounted for less than 10% of the reduced systemic glucose clearance in NIDDM subjects. Therefore, we conclude that muscle insulin resistance plays only a minor role in the reduced systemic glucose clearance found in NIDDM in the postabsorptive state and propose that reduced brain glucose clearance is largely responsible. PMID- 2227130 TI - Hepatic and extrahepatic responses to insulin in NIDDM and nondiabetic humans. Assessment in absence of artifact introduced by tritiated nonglucose contaminants. AB - It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previous studies of impure isotopes to measure glucose turnover. To determine hepatic and extrahepatic responses to insulin in the absence of these errors, steady-state glucose turnover was measured simultaneously with [6-3H]- and [6-14C]glucose during sequential 5- and 4-h infusions of insulin at rates of 0.4 and 10 mU.kg 1.min-1 in diabetic and nondiabetic subjects. At low insulin concentrations, [6 3H]- and [6-14C]glucose gave similar estimates of glucose turnover. Hepatic glucose release was equal to but not below zero in the nondiabetic subjects, but persistent glucose release (P less than 0.001) and decreased glucose uptake (P less than 0.001) was observed in the diabetic patients. At high insulin concentrations, both isotopes underestimated glucose turnover during the 1st h after initiation of the high-dose insulin infusion. More time (P less than 0.05) was required to reachieve steady state in NIDDM than nondiabetic subjects. At steady state, [6-3H]- but not [6-14C]glucose systematically underestimated (P less than 0.05) glucose turnover in both groups due to the presence of a tritiated nonglucose contaminant. The percentage of radioactivity in plasma due to tritiated contaminants was linearly related to turnover.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227131 TI - Metabolic effects of 1200-kcal diet in obese pregnant women with gestational diabetes. AB - Calorie restriction is widely used as a primary therapy for obese pregnant women with gestational diabetes. To better understand the metabolic consequences of marked calorie restriction, we performed a randomized prospective trial under metabolic ward conditions. Obese gestationally diabetic women were randomized to control (n = 5) and calorie-restricted (n = 7) groups. All patients consumed an approximately 2400-kcal/day diet during the 1st wk of the study, and at the end of the 1st wk, metabolic features of the two groups were statistically indistinguishable. During the 2nd wk, the control group continued to consume approximately 2400 kcal/day, whereas the calorie-restricted group consumed approximately 1200 kcal/day. Twenty-four-hour mean glucose levels remained unchanged in the control group (6.7 +/- 0.8 mM wk 1 vs. 6.8 +/- 0.8 mM wk 2), although they dropped dramatically in the calorie-restricted group (6.7 +/- 1.0 mM wk 1 vs. 5.4 +/- 0.5 mM wk 2, P less than 0.01). Fasting plasma insulin also declined in the calorie-restricted group (265 +/- 165 pM wk 1 vs. 145 +/- 130 pM wk 2), resulting in a significant change between groups (P less than 0.02). Surprisingly, fasting plasma glucose and glucose tolerance measured by the 3-h oral glucose tolerance test did not change within or between groups. Fasting levels of beta-hydroxybutyrate rose in the calorie-restricted group (290 +/- 240 microM wk 1 vs. 780 +/- 30 microM wk 2) but not in the control group (P less than 0.01). Finally, urine ketones increased significantly (P less than 0.02) in the calorie-restricted group, whereas they remained absent in the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227132 TI - Reduced membrane fluidity in platelets from diabetic patients. AB - Platelets from diabetic patients are hypersensitive to agonists in vitro. Membrane fluidity modulates cell function, and reduced membrane fluidity in cholesterol-enriched platelets is associated with platelet hypersensitivity to agonists, including thrombin. Decreased membrane fluidity of these platelets is attributed to an increased cholesterol-phospholipid molar ratio in platelet membranes. We examined the response of platelets from diabetic subjects to thrombin, platelet membrane fluidity, and platelet cholesterol-phospholipid molar ratio. Twelve poorly controlled diabetic subjects were compared with 12 age- and sex-matched control subjects. In response to a low concentration of thrombin, mean values for release of [14C]serotonin from washed prelabeled platelets were not significantly different between diabetic and control subjects, but in 8 of 12 diabetic subjects, the release response was greater than in their paired control subjects. Mean steady-state fluorescence polarization values in 1,6-diphenyl 1,3,5-hexatriene-labeled platelets prepared from diabetic subjects were significantly greater than in control subjects; this indicates a decreased membrane fluidity in platelets from diabetic subjects. Total or very-low-density (VLDL), low-density (LDL), or high-density (HDL2, HDL3) lipoprotein cholesterol concentrations in plasma were not significantly different between groups; however, the ratio of VLDL + LDL to HDL2 + HDL3 was significantly greater in diabetic than in control subjects. There was no difference in the total platelet cholesterol-phospholipid molar ratio between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227133 TI - Relationship between blood pressure and urinary albumin excretion in development of microalbuminuria. AB - Two hundred nine consecutive normotensive insulin-dependent diabetic (IDDM) patients were followed prospectively from November 1982 to January 1988. Patient urinary albumin excretion rate (UAE) had to be normal (less than 30 mg/24 h) on at least two occasions before inclusion in the study. Patients were aged 18-50 yr with a duration of diabetes of 10-30 yr. UAE was measured every 4 mo, and supine blood pressure was measured annually. Two hundred five patients completed the study. Five years later, 15 patients had developed persistent microalbuminuria with median UAE greater than 30 mg/24 h for at least 2 yr (group 2), and 190 patients stayed normoalbuminuric (group 1). Although within normal range, initial UAE was significantly elevated in group 2 compared with group 1 (mean 19 mg/24 h [range 15-23 mg/24 h] vs. 11 mg/24 h [10-12], 95% confidence interval [CI], P less than 0.001). Initially, there was no difference in blood pressure between group 2 (mean systolic 122 mmHg [117-127], diastolic 80 mmHg [76-84]) and group 1 (mean 126 mmHg [124-128], 79 mmHg [78-80], 95% CI), and a significant increase in diastolic blood pressure could first be detected during the 3rd yr of persistent microalbuminuria (mean systolic 132 mmHg [124-140], diastolic 85 mmHg [81-89] vs. 128 mmHg [126-130], 79 mmHg [78-80], P less than 0.05). Initial hemoglobin A1c was significantly elevated in group 2 compared with group 1 (9.6% [8.8-10.4] vs. 8.5% [8.3-8.7], P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227134 TI - Insulin-receptor autophosphorylation and endogenous substrate phosphorylation in human adipocytes from control, obese, and NIDDM subjects. AB - We identified a possible endogenous substrate (pp185) of the insulin-receptor kinase in human adipocytes by treating intact cells with insulin and immunoblotting the cellular extracts with polyclonal antiphosphotyrosine antibody. This 185,000-Mr protein was phosphorylated on tyrosine residues in response to insulin in both rat and human adipocytes. The time course of pp185 phosphorylation at 37 degrees C was rapid and corresponded closely to insulin receptor autophosphorylation but preceded insulin-stimulated glucose transport. Unlike many growth factor receptors, including the insulin receptor, pp185 was not adsorbed to wheat-germ agglutinin. We found that pp185 phosphorylation occurred at 12 degrees C and that the phosphoprotein was associated with both cytoplasmic and membrane fractions at this temperature. Furthermore, pp185 phosphorylation was induced to the same extent as insulin by vanadate and hydrogen peroxide, compounds previously shown to mimic the biologic effects of insulin. In addition, dose-response analysis of insulin-stimulated glucose transport, receptor autophosphorylation, and pp185 phosphorylation resulted in ED50 values of 0.3, 12, and 12 ng/ml, respectively. These results demonstrate the magnitude of "spare" autophosphorylation and pp185 phosphorylation with respect to glucose transport stimulation in human adipocytes. To determine whether the insulin resistance characteristic of non-insulin-dependent diabetes mellitus (NIDDM) and obesity is associated with a defect in receptor autophosphorylation and/or endogenous substrate phosphorylation, we estimated the extent of beta subunit and pp185 phosphorylation in adipocytes from NIDDM, obese, and healthy subjects. Although the efficiency of coupling between receptor activation and pp185 phosphorylation was normal in obesity and NIDDM, the capacity for insulin receptor autophosphorylation was approximately 50% lower in NIDDM subjects compared with nondiabetic obese or lean subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227135 TI - Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide. AB - During hyperinsulinemic glucose-clamp studies, intravenous infusion of calcitonin gene-related peptide (CGRP) in rats antagonized the ability of insulin to stimulate peripheral glucose disposal by 52% (196 +/- 7.2 vs. 105 +/- 10.5 mumol.kg-1.min-1, P less than 0.05) and to inhibit hepatic glucose output by 54% (P less than 0.01). CGRP also inhibited the in vitro effects of insulin to stimulate hexose uptake in cultured BC3H1 myocytes at all insulin concentrations studied. Amylin is a peptide isolated from amyloid deposits in pancreatic islets of type II (non-insulin-dependent) diabetic subjects, is present in normal beta cells, and bears a striking homology to CGRP. When synthetic human amylin was infused during clamp studies, it inhibited the ability of insulin to stimulate glucose disposal by 56% (96.9 +/- 9.4 vs. 42.4 +/- 5.0 mumol.kg-1.min-1, P less than 0.05) and to suppress hepatic glucose output by 64%. Therefore, amylin and CGRP can cause insulin resistance in vivo and may be implicated in insulin resistant states such as type II diabetes mellitus. PMID- 2227137 TI - 'Future directions in research and prevention'. PMID- 2227136 TI - High frequency of aspartic acid at position 57 of HLA-DQ beta-chain in Japanese IDDM patients and nondiabetic subjects. AB - The HLA-DQ beta-chain (DQB1) genes of 72 Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 85 control subjects were studied with polymerase chain-reaction (PCR) amplification and allele-specific oligonucleotide hybridization. DQW4 (DQBBlank) and DQw9 (DQB3.3) were increased in IDDM patients compared with the control subjects, and DQB1.2, DQB1.9, and DQw7 (DQB3.1) were decreased. Thirty-five (48.6%) IDDM patients had both alleles carrying an aspartic acid at position 57 of the DQ beta-chain (Asp 57), 35 (48.6%) were Asp 57/non-Asp 57 heterozygous, and 2 (2.8%) had non-Asp 57 alleles only. Of 85 control subjects, the respective values for these three genotypes were 49 (57.6%), 29 (34.1%), and 7 (8.2%), respectively. The high frequency of Asp 57 alleles in both IDDM and control subjects contrasts with data for Whites. Therefore, the Asp 57 hypothesis that the presence of an aspartic acid at position 57 of DQ beta-chain provides protection against developing IDDM is not tenable for Japanese IDDM patients. The DRB1 gene, particularly position 57 of the DR beta-chain, may contribute to IDDM susceptibility in Japanese. PMID- 2227138 TI - Light-gazing by visually impaired children. AB - This study assessed the prevalence and characteristics of light-gazing by all visually impaired children referred during a 2 1/2-year period. Light-gazing (compulsive staring into lights) is one of the many clinical signs of cortical visual impairment (CVI), and in the present study it occurred in 60 per cent of children with CVI. The authors believe that light-gazing by any child with ocular lesions indicates some degree of CNS involvement. Visually impaired children who flicker their fingers in front of their eyes against a light source demonstrate an extension of this compulsive behaviour. This and other studies suggest that blind mannerisms have specific neuropathological substrata and therefore are useful clinical signs. PMID- 2227139 TI - Cervical auscultation of suckle feeding in newborn infants. AB - The authors recorded the sound signals during suckle feeding of six normal infants within the first two postnatal days. The sounds were recorded onto a cassette tape-recorder from a small microphone attached to the infant's neck, then displayed on an oscilloscope and analysed by digital signal processing techniques. These displays demonstrated acoustic patterns and temporal relationships which are not otherwise audible. The method and findings are described in detail, and the method should be useful in the clinical investigation of feeding and swallowing problems associated with more subtle neurological impairment and preterm birth. PMID- 2227140 TI - Multiple sclerosis in childhood: contribution of serial MRI to earlier diagnosis. AB - The authors report six children (five girls, one boy) aged 11 to 13 years, of whom four had clinically definite multiple sclerosis (MS) and two had laboratory supported definite MS. All had brain white matter abnormalities indicative of MS. In three cases, positive findings on the first MRI contributed significantly to their early diagnosis. Follow-up MRI studies over an average period of five months detected morphological changes in three of the children, although there was no concomitant clinical evidence. This raises the question of whether changes in clinically 'silent' lesions on follow-up MRI are antecedents of the essential MS criterion of dissemination over time, which could lead to earlier diagnosis of childhood MS. With cranial computerized tomography (CT) during the first clinical attack, a large focus with a lamellar structure mimicked a brain tumour in two patients. As CT also misses additional small lesions, it should no longer be used as the primary diagnostic method. PMID- 2227141 TI - Control of isometric muscle activity in cerebral palsy. AB - Voluntary control of muscle contraction was examined in five adults with cerebral palsy, who were required to track a moving target by continuously varying the level of isometric contraction of elbow flexor muscles (measured by EMG). First performance varied from minimal control to almost normal control, depending on the severity of disability. Practice over 12 weeks reduced inappropriate muscle activity in the most disabled patients, but there was no increase in appropriate muscle activity for any patient beyond that observed after the first few minutes of tracking. Thus their ability to translate a visual response into the appropriate motor activity was impaired, and there was no evidence of potential to overcome this. This supports the authors' earlier proposal that impairment of sensory-motor learning is the primary cause of functional disability in cerebral palsy. The EMG tracking task may provide a technique for assessing the ability of individuals with cerebral palsy to control muscle contraction. PMID- 2227142 TI - Postoperative electromyographic function of tendon transfers in patients with cerebral palsy. AB - Electromyographic studies were performed on 13 patients with cerebral palsy before and after flexor carpi ulnaris transfers. No changes in activity of the extensor digit communis were noted in the transferred muscles. This further validates the rationale of pre-operative planning based on such studies. PMID- 2227143 TI - Rapid anti-epileptic drug assay. AB - The usefulness of rapid anti-epileptic drug assay in a paediatric neurology clinic was assessed. Compared with a method in which results were not available for seven to 10 days, there was an increased likelihood that levels would be within the target range, particularly for carbamazepine. Increased parental discussion, and therefore involvement with dosage, was possible. Management of children receiving phenytoin was more efficient and non-compliance could be dealt with immediately. When anti-epileptic drug levels are measured, rapid assay, with results available while the patient is still in the clinic, should be a standard facility. PMID- 2227144 TI - Fukuyama congenital muscular dystrophy in two Australian female siblings. AB - The clinical course of two female siblings with congenital muscular dystrophy is briefly described, and includes congenital cerebral malformations consisting of pachygyria, polymicrogyria and white matter abnormalities. The first sibling died in infancy; the second is now 18 years of age. The changes found at autopsy in the first sibling are identical to MRI changes in the surviving sibling. PMID- 2227145 TI - Old syndromes and new cytogenetics. AB - This annotation has been confined to well-established clinical syndromes with recently discovered chromosomal etiologies. It deliberately omits retinoblastoma, the oft-cited paradigm of a contiguous gene syndrome, since it is usually inherited as a Mendelian single gene disorder. However, it was recognition of both the deletion of band q14 of chromosome 13 in mentally retarded children with retinoblastoma, and the linkage of retinoblastoma with the genetic marker esterase D, which resulted in the eventual cloning of the gene. Also omitted are microdeletions of the X chromosome. These disorders are seen primarily in males, who manifest the phenotypic effects of the deletion of the loci of various combinations of adjacent genes: Duchenne muscular dystrophy, glycerol kinase deficiency, adrenal hypoplasia, optic albinism, hypogonadotropic hypogonadism and anosmia (Kallman syndrome), chondrodysplasia punctata and ichthyosis. Many are also mentally retarded. The third group omitted are Mendelian disorders occurring with atypical mental retardation (not usually part of the disorder), the presumption being that they include small deletions. It is expected that other contiguous gene syndromes will be recognized eventually; Rubinstein-Taybi and Cornelia de Lange syndromes are prime candidates. Why do deletions have such dramatic consequences when a normal homologue of the region is present? If their effects were due to the uncovering of recessive genes, we would expect to see greater variations in phenotype among carriers, including normal individuals whose deletions were masked by the protective effects of dominant alleles in the homologous regions. Imprinting--the 'stamping' of a gene as it passes through the germ line--provides a more satisfactory explanation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227146 TI - Further thoughts on autistic tendencies. PMID- 2227147 TI - Correlation between temperature and infants' gross motor development. PMID- 2227148 TI - EPC European Pancreatic Club. XXIInd meeting. Basel, October 15-17, 1990. Abstracts. PMID- 2227149 TI - Toxicological information series, IV. Information resources for chemical emergency response. AB - The need for rapidly available information by community agencies responding to chemical emergencies (leaks, spills, releases, fires, explosions, etc.) can be met by a number of resources. These resources include local poison control centers, the Toxicology Data Network (National Library of Medicine), the Agency for Toxic Substances and Disease Registry, ATSDR/NLM's ANSWER, the National Chemical Response and Information Center, the National Pesticide Telecommunications Network, The National Response Center (U.S. Coast Guard), the Federal Emergency Management Agency, the U.S. Environmental Protection Agency, the National Safety Council, private-sector database vendors, and textbooks addressing hazardous substances. PMID- 2227150 TI - Aldicarb immunotoxicity: functional analysis of cell-mediated immunity and quantitation of lymphocyte subpopulations. AB - Adult female B6C3F1 mice received distilled water only or water containing 1.0, 10, or 100 ppb of aldicarb daily for 34 days. The target concentration of aldicarb present in the 100 ppb dosing solution was analytically verified. To further develop an immune profile of this compound, following aldicarb exposure, the ability of splenic natural killer cells and specifically sensitized cytotoxic T-lymphocytes to lyse YAC-1 lymphoma and P815 tumor cells, respectively, was evaluated. To supplement the functional assays, the impact of aldicarb exposure on the percentages and absolute numbers of total T-cells, T-suppressor, T-helper, and B-cells was evaluated. The absence of statistically significant effects on any of these parameters supports earlier reports that aldicarb does not result in adverse effects on the immune system of mice. PMID- 2227152 TI - Variability of a mouse ear swelling test (MEST) in predicting weak and moderate contact sensitization. AB - An investigation was conducted at two independent laboratories for the purpose of evaluating the ability of a mouse ear swelling test (MEST), previously developed and validated by S.C. Gad. B.J. Dunn, D. W. Dobbs, C. Reilly, and R.D. Walsh (1986, Toxicol. Appl. Pharmacol. 84, 93-114), to predict contact sensitization induced by weak to moderate contact sensitizers. Twenty-six coded chemicals, 23 with weak to strong potential to induce sensitization in animals and/or humans and 3 negative controls, were investigated. Each laboratory tested 18 materials: 10 chemicals were common to both labs and 16 chemicals were divided so that 8 were unique to each of the two labs. The methods and chemicals utilized were the same as those used and reported by Gad et al. (1986) and, therefore, data generated from this investigation were compared to results from their research. Contrary to results reported by Gad and co-workers, findings from the present study suggest that this MEST is a useful model for identifying strong contact sensitizers, but is not reliable for detecting weak to moderate allergens. PMID- 2227151 TI - Clearance, translocation, and excretion of beryllium following acute inhalation of beryllium oxide by beagle dogs. AB - Beagle dogs inhaled radiolabeled beryllium oxide (7BeO) particles that were calcined at either 500 or 1000 degrees C, resulting in either high (mean of 50 micrograms/kg body wt) or low (mean of 17 micrograms/kg body wt) initial lung burdens (ILBs) of both preparations of BeO. Levels of beryllium in whole body, tissue, and excreta were measured by external gamma-ray counting. Dogs were euthanized in pairs at 8, 32, 64, and 180 days after exposure to determine beryllium distribution in tissues. Beryllium oxide calcined at 1000 degrees C was retained more tenaciously in the lungs (62% of the ILB retained at 180 days after exposure) than BeO calcined at 500 degrees C (14% of the ILB retained at 180 days after exposure). Most of the beryllium that was cleared from the lungs and not excreted was translocated to the tracheobronchial lymph nodes, skeleton, liver, and blood. More beryllium was translocated to the skeleton and liver at 180 days after inhalation of BeO prepared at 500 degrees C than at 1000 degrees C. The predominant mode of excretion at early times after exposure was through the feces, with urinary excretion assuming predominance at later times. These data are important for interpreting the toxic effects of beryllium in the exposed dogs. Furthermore, because little is known concerning the retention and clearance of inhaled beryllium in man, these results provide information that may be used to understand the disposition of beryllium in accidentally exposed humans. PMID- 2227153 TI - Taurine failed to protect against the embryotoxic effects of isotretinoin in the rat. AB - Experimental evidence exists to indicate that retinoids may act as detergents to disrupt biological membranes. Taurine, an amino sulfonic acid, has been shown to possess membrane-stabilizing and cytoprotective properties. This study was undertaken to test whether taurine coadministered with isotretinoin might be able to protect against the teratogenic effects of the retinoid. Our study failed to find any support for this speculation. Whether challenged against a 75 (mildly teratogenic) or 150 (very teratogenic) mg/kg/day dose of isotretinoin, taurine for the most part worsened the retinoid embryotoxicity. While in a few combinations taurine decreased the resorption or malformation rate associated with isotretinoin, the decrease was, at best, marginal. In no case was taurine able to decrease these rates to those noted in the controls. PMID- 2227154 TI - Preclinical toxicological evaluation of fostriecin, a novel anticancer antibiotic, in rats. AB - Fostriecin, a novel anticancer antibiotic produced by Streptomyces pulveraecus, is believed to act via inhibition of topoisomerase II. Single-dose intravenous administration to rats at dose levels of 8.8 to 48 mg/kg resulted in lethality at dose levels of 35 mg/kg and higher. Major toxic effects were observed primarily at 17.5 mg/kg and higher, were reversible, and consisted of bone marrow hypocellularity, leukopenia, neutropenia, thrombocytopenia, and diffuse necrosis of various lymphoid tissues. The kidney was also identified as a target organ. Renal effects were observed primarily at 20 mg/kg, were reversible, and included increases in serum BUN, creatinine, and 24-hr glucose excretion. Twenty-four-hour excretion of Na+, K+ and urine osmolality were decreased postdosing at 10 and 20 mg/kg. Renal lesions, observed primarily at 20 mg/kg, consisted of vacuolization and necrosis of proximal and distal tubular epithelium at the corticomedullary junction extending into the medulla. Repeated daily intravenous administration of fostriecin for 5 days to rats at dose levels of 2.5 to 26.5 mg/kg resulted in death at 10 mg/kg and above and similar hematologic, bone marrow, lymphoid tissue, and renal changes as observed in the single-dose study. Hematological, bone marrow, lymphoid, and renal changes observed in rats were consistent with the cytotoxic mechanism of action of the compound. PMID- 2227155 TI - Modulation of glucose metabolism in isolated rat hepatocytes by 1,1,1,2 tetrafluoroethane. AB - The thermodynamic behavior and lack of ozone-depleting potential of 1,1,1,2 tetrafluoroethane (R-134a) suggest it as a likely replacement for dichlorodifluoromethane (R-12), now used as the refrigerant in many air conditioning systems. To further the presently incomplete toxicological analysis of R-134a, the effects of R-134a on cell viability and functional competence of glucose metabolism were evaluated in suspension cultures of hepatocytes derived from fed or fasted rats. R-134a concentrations up to and including 75% (750,000 ppm) in the gas phase of sealed culture flasks did not produce evidence of cytolethality (LDH leakage) following 2 hr of exposure; in contrast, halothane (1,1,1-trifluoro-2-bromo-2-chloroethane) caused cell death at a gas phase concentration of only 1250 ppm. In hepatocytes isolated from fed rats. R-134a at concentrations of 12.5 to 75% increased glycolysis (production of lactate + pyruvate) in a concentration-dependent manner; no effect was observed at 5%. At 25%, R-12 and 1,1,2,2-tetrafluoro-1,2-dichloroethane (R-114) were of equal potency to R-134a in stimulating glycolysis: 1,1,1,2,2-pentafluoro-2-chloroethane (R-115) depressed glycolysis slightly. Halothane, at concentrations as low as 300 ppm, markedly increased rates of glycolysis. Glucose production by hepatocytes of fed rats was decreased by R-134, R-12, and R-114 only at concentrations of 25% or more. On the other hand, halothane (greater than or equal to 300 ppm) potently decreased glucose production by hepatocytes. In cells isolated from livers of fasted rats, R-134a exposure inhibited gluconeogenesis in a concentration dependent manner although this effect was not significant until R-134a concentrations reached 12.5%. Comparative potency studies showed that R-134a, R 12, or R-114 (25% gas phase) inhibited gluconeogenesis about equally while as little as 300 ppm halothane was effective and R-115 (25%) was without effect. Considering that the threshold for alteration of the rate of glucose metabolism in this in vitro paradigm is about 12.5% R-134a, we conclude that toxicologically significant alteration of glucose-linked bioenergetics is unlikely at the levels of R-134a exposure anticipated in workplace or environment. PMID- 2227157 TI - The structure-dependent effects of heptachlorodibenzofuran isomers in male C57BL/6 mice: immunotoxicity and monooxygenase enzyme induction. AB - The dose-response effects of the 1,2,3,4,6,7,8-, 1,2,3,4,7,8,9-, 1,2,3,4,6,8,9-, and 1,2,3,4,6,7,9-heptachlorodibenzofurans (HpCDFs) on the splenic plaque-forming cell (PFC) response to sheep erythrocytes and on the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin-O-deethylase (EROD) activities were determined in male C57BL/6 mice. The ED50 values for the decrease in the PFCs/spleen, the number of PFCs/10(6) viable cells, and the induction of AHH and EROD activities were 1,2,3,4,6,7,8-HpCDF, 0.011, 0.018, 0.11, and 0.315 mumol/kg, respectively; 1,2,3,4,7,8,9-HpCDF, 0.012, 0.054, 0.70, and 0.20 mumol/kg, respectively; 1,2,3,4,6,7,9-HpCDF, 1.2, 1.3, greater than 43, and greater than 43 mumol/kg, respectively; 1,2,3,4,6,8,9-HpCDF, 1.5, 3.4, 22, and 22 mumol/kg, respectively. It was apparent from these studies that the 2,3,7,8-substituted HpCDF isomers (1,2,3,4,6,7,8- and 1,2,3,4,7,8,9-) were significantly more potent than the compounds which contained only three lateral C1 groups. These results were obtained using a multiple dosing regimen in which 10 separate doses of the HpCDF isomers were administered to the mice by intraperitoneal injection over a period of 12 days. However, when the mice were treated with a single dose of an HpCDF congener, which was equivalent to the total dose used in the multiple dose study, the responses were comparable. A comparison of the relative immunotoxic potencies of the 2,3,7,8-substituted HpCDFs and 2,3,7,8-tetrachlorodibenzo-p-dioxin showed that the latter compound was approximately 10 times more active than the HpCDFs. PMID- 2227156 TI - Carbendazim-induced alterations of reproductive development and function in the rat and hamster. AB - We are developing a data base that will allow us to select endpoints that would be useful in the detection of reproductive toxicity in a multigenerational test. In this effort, carbendazim (MBC), a known reproductive toxicant, was administered to male and female rats from weaning, through puberty, gestation, and lactation. A similar study was conducted with hamsters. In rats, MBC was administered at 0, 50, 100, 200, or 400 mg/kg/day. Hamsters were dosed at 0 or 400 mg/kg/day. In the parent (P0) generation, landmarks of puberty were measured. In females, estrous cyclicity, litter size, the number of implants, organ weights, and histology were assessed. Our assessment of the male rat included organ weights, testicular and epididymal sperm counts, a quantitative measure of sperm motility, sperm morphology, testicular histology, and endocrine measures. The growth, viability, and reproductive function of the offspring (F1) were observed during a 4-month period of continuous breeding. In the P0 of both species. MBC did not alter pubertal development, growth, or viability. The reproductive potential of the rats treated with MBC at 200 and 400 mg/kg/day was reduced due to effects on sperm production and fetal viability. In the male rat, MBC treatment markedly altered sperm morphology, testicular and epididymal weights, and sperm numbers and testicular histology. Fertility, sperm motility, and hormonal levels were altered, primarily in the males with very low sperm counts. The ability to conceive did not appear to involve a female factor. In P0 female rats, MBC administration caused postimplantation losses in the high-dosage groups and a few malformed rat pups were found in the litters from the 100 and 200 treatment groups. MBC was less toxic to the hamster than the rat. The only reproductive effects induced by MBC treatment were on sperm measures. Fertility of the P0 generation and fetal and neonatal (F1) viability were not decreased by MBC administration. In the male rat, testis weight, sperm numbers in the cauda epididymis and testis and sperm morphology were sensitive to the effects of MBC. In females, counting implantation scars at necropsy was useful, as this information allowed us to confirm pregnancy and identify postimplantation losses induced by MBC administration. PMID- 2227158 TI - Effect of inhaled azodicarbonamide on F344/N rats and B6C3F1 mice with 2-week and 13-week inhalation exposures. AB - Azodicarbonamide (ADA), a compound used in the baking and plastics industries, has been reported to cause pulmonary sensitization and dermatitis in people. Two week repeated and 13-week subchronic inhalation exposures of F344/N rats and B6C3F1 mice to ADA were conducted to determine the toxicity of inhaled ADA. The mean air concentrations of ADA in the 2-week studies were 207, 102, 52, 9.4, or 2.0 mg/m3. No exposure-related mortality nor abnormal clinical signs were observed in rats or mice during or after exposure. The terminal body weights were slightly depressed in the highest exposure group. Liver weights were lower in male rats exposed to 200 mg ADA/m3. No significant lesions were noted on either gross or histologic evaluation of rats or mice. In the 13-week subchronic study, the mean air concentrations of ADA were 204, 100, or 50 mg/m3. No mortality or clinical signs related to exposure were observed. The terminal body weights of exposed rats were not significantly different from those of control rats but were significantly depressed in mice exposed to 100 or 200 mg ADA/m3. No histopathological lesions were noted in mice. Lung weights were increased and enlarged mediastinal and/or tracheobronchial lymph nodes were noted in rats exposed to 50 mg ADA/m3. No exposure-related lesions were observed microscopically in rats exposed to 100 or 200 mg ADA/m3. All rats in the 50 mg ADA/m3 exposure group only had lung lesions that consisted of perivascular cuffing with lymphocytes and a multifocal type II cell hyperplasia, suggesting a possible immune reaction to an antigen in the lung. Viral titers for rats exposed to 50 mg ADA/m3 were negative for Sendai virus and pneumonia virus of mice, which produce similar lesions. The possibility of an unknown viral antigen causing this lesion cannot be eliminated. Lung tissue from male rats was analyzed for ADA and biurea, the major metabolite of ADA. No ADA was detected. The amount of biurea in the lungs increased nonlinearly with increasing exposure concentration, suggesting that clearance was somewhat impaired with repeated exposures. However, even at the highest exposure concentration, this amount of biurea was less than 1% of the estimated total ADA deposited over the exposure period. In summary, ADA is rapidly cleared from the lungs, even when inhaled at concentrations up to 200 mg/m3. Exposure to ADA for up to 13 weeks did not appear to be toxic to rodents. PMID- 2227159 TI - Estimation of epidermal carcinogenic potency. AB - This report compared two statistical methods of estimating tumor latency, the Weibull distribution model and the Kaplan-Meier method. Parallelism of dose response curves of different materials and quantitative reproducibility of dermal carcinogenesis data were also examined. The Weibull method has the advantage of producing parameter estimates, even when tumor yield is low. The Kaplan-Meier method, on the other hand, is free of distribution assumptions. Overall, since the comparisons of potency are made on the basis of parameters from the same assumed distribution on the same strain of animal, the Weibull estimates are favored. A comparison of dose-response data for benzo[a]pyrene and catalytically cracked clarified oil indicated that the slopes of the two dose-response curves were significantly different. Thus the relative carcinogenic potencies of different materials vary with dose, and potency comparisons must necessarily be dose-specific. The quantitative reproducibility of dermal carcinogenesis bioassays was also assessed. The dose-response curves from the three studies of one material had significantly different slopes. Thus the results suggested that there were sources of biological variability which could contribute to experimental error. PMID- 2227160 TI - Arsine: absence of developmental toxicity in rats and mice. AB - Arsine gas is a potent hemolytic agent but the effects of exposure to tolerated concentrations on pregnancy and prenatal development have not been reported. In the present evaluation, groups of bred mice and rats were exposed to arsine at concentrations of 0.025, 0.5, or 2.5 ppm on Gestation Days (gd) 6 through 15. Animals were killed on gd 17 (mice) or on gd 20 (rats) and endpoints of maternal and developmental toxicity were evaluated. In rats, maternal spleens were enlarged in the 2.5 ppm group and there was a decrease in packed red cell volume in pregnant rats. Fetuses weighed more than in the control group but other endpoints of developmental toxicity were not affected by arsine exposure. In another experiment involving separate groups of rats, the arsenic content of maternal blood and fetal livers increased with increasing atmospheric arsine concentrations, as assessed on gd 20. In mice, maternal spleen size was significantly increased in the 2.5 ppm group. The number of live fetuses, mean fetal body weight, and percentages of resorptions or malformations per litter were not affected by arsine exposure. In conclusion, arsine at atmospheric concentrations that caused increases in maternal spleen size and measurable levels of arsenic in maternal blood and fetal livers did not adversely affect endpoints of developmental toxicity. PMID- 2227161 TI - Inhalation toxicity studies of cobalt sulfate in F344/N rats and B6C3F1 mice. AB - Groups of 10 F344/N rats and B6C3F1 mice of each sex were exposed to cobalt sulfate heptahydrate aerosols of 0, 0.3, 1.0, 3.0, 10, or 30 mg/m3, 6 hr per day, 5 days per week, for 13 weeks. All rats and female mice and all but 2/10 male mice exposed at the top concentration survived to the end of the studies. Polycythemia was observed in exposed rats but not in mice. Sperm motility was decreased in mice exposed at 3 mg/m3 (the lowest concentration evaluated) and at higher concentrations, and increased numbers of abnormal sperm and decreased testis and epididymal weights occurred in mice exposed to 30 mg/m3. Cobalt content in the urine of rats increased with increasing atmospheric cobalt exposure. Primary histopathologic effects were limited to the respiratory tract. Lesions in rats and mice included degeneration of the olfactory epithelium, squamous metaplasia of the respiratory epithelium, and inflammation in the nose; inflammation, necrosis, squamous metaplasia, ulcers (rats), and inflammatory polyps (rats) of the larynx; metaplasia of the trachea (mice); and fibrosis, histiocytic infiltrates, bronchiolar epithelial regeneration, and epithelial hyperplasia in the alveoli of the lung. The most sensitive tissue was the larynx, with squamous metaplasia observed in rats and mice at the lowest exposure concentration of 0.3 mg/m3. Thus, a no-observed-adverse-effect level was not reached in these studies. PMID- 2227162 TI - Toxic interactions of the munitions compounds TNT and RDX in F344 rats. AB - The potential toxic interactions in F344 rats of the munitions compounds trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) were examined following their coadministration in the diet. Groups of 10 rats per sex received TNT at doses of 5 or 125 mg/kg/day, RDX at doses of 30, 100, or 300 mg/kg/day, and combinations thereof for 13 weeks. Thirty rats per sex served as controls. Toxicologic endpoints included clinical observations, body weight, food consumption, hematology, clinical chemistry, organ weights, and tissue morphology. The major toxic effects following dietary administration of TNT to rats included anemia, hypercholesterolemia, and hepatomegaly, splenomegaly, and testicular atrophy with their accompanying histologic lesions. RDX intoxication in rats included hypotriglyceridemia, behavioral changes, and mortality. Most of the toxic effects of these chemicals were partially antagonized following their coadministration. PMID- 2227163 TI - Degeneration and recovery of rat olfactory epithelium following inhalation of dibasic esters. AB - Dibasic esters (DBE) are solvent mixtures used in the paint and coating industry. To evaluate the potential subchronic toxicity of DBE, groups of male and female rats were exposed for periods of up to 13 weeks to DBE concentrations of 0, 20, 76, or 390 mg/m3. After approximately 7 and 13 weeks of exposure, 10 rats per sex per group were subjected to clinical chemical, hematological, and urine analyses. Following 7 or 13 weeks of exposure, 10 or 20 rats per sex per group, respectively, were euthanized. An additional 10 rats were euthanized following a 6-week recovery period. A standard profile of tissues, including four levels of nasal cavity, was evaluated histopathologically. After 7 weeks of exposure, slight degeneration of the olfactory epithelium was observed in both male and female rats at 76 and 390 mg/m3. After 13 weeks, degeneration of the olfactory epithelium was present at all DBE concentrations in female rats, but only at the mid and high concentrations in male rats. The severity and incidence of the lesions were concentration related for both sexes with female rats being more sensitive than males. Following the recovery period, histological changes compatible with repair in the olfactory mucosa included an absence of degeneration, focal disorganization of the olfactory epithelium, and respiratory metaplasia. All other tissues were macroscopically normal. No other signs of toxicity were indicated by the other parameters evaluated. Inhalation studies of other esters demonstrate similar pathology in the olfactory epithelium. Since olfactory mucosa is rich in carboxylesterase activity, acids may be the toxic metabolites of these compounds. This hypothetical mechanism may explain the sensitivity of olfactory tissue to the effects of DBE. PMID- 2227165 TI - Statistical analyses for the carcinogenesis bioassay. PMID- 2227164 TI - Subchronic inhalation study with vinyl fluoride: effects on hepatic cell proliferation and urinary fluoride excretion. AB - Vinyl fluoride is used widely in the manufacture of fluoropolymers. Based in part on the structural similarity of vinyl fluoride to the hepatocarcinogens vinyl chloride and vinyl bromide, a TSCA Section 4 test rule mandated the testing of vinyl fluoride for oncogenicity. This report presents the results of a 90-day inhalation study in rats and mice with vinyl fluoride designed to set test concentrations for a subsequent oncogenicity study. Groups of 15 male and female rats and mice were exposed 6 hr per day, 5 days per week for approximately 90 days to target concentrations of 0, 200, 2000, or 20,000 ppm vinyl fluoride. Clinical chemical, hematological, and urine analyses were performed on rats after 45 and 90 days of exposure. A hematological evaluation was performed on mice following 45 and 90 days of exposure. A complete gross and microscopic evaluation was conducted at the end of the study. After 93 days on test, groups of five rats and five mice per sex were implanted with osmotic minipumps containing [3H]thymidine and were exposed for an additional 5 days to measure cell proliferation in liver, kidney, lung, and nasal cavity tissues. Results of the histopathological, clinical chemical, and hematological evaluations showed no significant effects of vinyl fluoride exposure at any concentration following either 45 or 90 days of exposure. A concentration-related increase in fluoride ion in urine was observed in rats at 45 and 90 days of exposure. A plateau in urinary fluoride excretion was observed at approximately 2000 ppm, suggesting saturation of vinyl fluoride metabolism. Vinyl fluoride-related cell proliferation effects were largely restricted to liver. Hepatic cell proliferation in male and female rats and mice was elevated at all concentrations. The response was similar at concentrations of either 2000 or 20,000 ppm and was consistent with concentration-response relationships for other haloethylenes. Taken together, the urinary fluoride excretion and hepatic cell proliferation data suggest a mechanistic link between the two effects. On the basis of these findings and experience with other haloethylenes, concentrations of vinyl fluoride to be tested for oncogenicity should be chosen such that the full linear range of the concentration-response curve is evaluated. The present study demonstrates through example the value of incorporating cell proliferation studies in standard testing protocols. PMID- 2227166 TI - New ideas for geriatric fellowships. PMID- 2227167 TI - The nutritional content of pharmaceutical company sponsored promotions. PMID- 2227168 TI - Assessment of the Federal Grant Program for the Establishment of Departments of Family Medicine. AB - As part of an evaluation of the Federal Establishment of Departments of Family Medicine Grant Program, nine departments of family medicine were visited from March to May 1988 to assess their development in the academic setting and to evaluate the role of the federal program in that developmental process. The study found that grant support has been useful in enhancing the status of family medicine by aiding research and curriculum development, supporting administrative infrastructure, and fostering other topics specific to individual departments. The flexibility with which departments can seek funds for specific needs makes broad measures of success impractical; however, it appears that funds from this grant program have been reasonably effective in advancing the academic stature of departments of family medicine. It is concluded from the study that the program should be continued and that its inherent flexibility should be preserved. PMID- 2227169 TI - The Upper Peninsula Program: a successful model for increasing primary care physicians in rural areas. AB - In 1974, Michigan State University established the Upper Peninsula Medical Education Program (UP) to improve the physician supply in rural areas of Michigan by training students in a rural, practice-based setting. Practicing graduates of the program (N = 28) were surveyed by mail and their responses compared to a random sample of downstate MSU graduates (N = 57) with regard to practice location, specialty choice, hometown, and medical education and training. UP Program graduates showed a tendency to rural origin and chose rural practice and primary care specialties, especially family practice, more often than did their downstate colleagues. Responses of UP graduates suggested that rural residency locations would lead to increased numbers of rural practitioners. The rural UP Program has been successful to date in training medical students who ultimately pursue careers in rural primary medicine. PMID- 2227170 TI - Qualitative and quantitative methods for the assessment of clinical preceptors. AB - The improvement of clinical teaching skills has consistently been an important focus of faculty development in family medicine. Successful faculty development programs depend on an understanding of the components of clinical teaching and a profile of the strengths and weaknesses of each faculty member with respect to these components. In this study a system was developed to identify and measure specific faculty characteristics of inpatient preceptors. Complementary quantitative and qualitative approaches were employed. An analysis and comparison of the two approaches suggest that the measures result in a similar ranking of faculty, but that the qualitative approach identifies individual faculty strengths and weaknesses, which are more useful for providing feedback to stimulate and guide change. PMID- 2227171 TI - Ideology and reality of continuity of care. AB - The concept of continuity of care is part of the framework on which the ideology and teaching of family practice is based. The purpose of the present study was to evaluate the ideals and reality of continuity of care as perceived by Norwegian family physicians. A representative sample of 207 physicians answered a mailed questionnaire related to continuity of care. Eighty percent of the physicians found the concept of continuity important or very important to the ideology of family practice. There were, however, significant statistical and clinically important discrepancies between ideals and reality. If standards are too ambitious or unrealistic to achieve, they often become counterproductive. Two basic ways to correct this discrepancy are discussed: improving reality by increasing chronological care and lowering the ideals by de-emphasizing comprehensive care. The ideals of continuity of care in family practice were set more than 20 years ago. As the field of family practice matures, more realistic goals may be indicated to prevent individual professional burnout and loss of credibility as a specialty. PMID- 2227172 TI - A randomized controlled evaluation of a psychosocial intervention in adults with chronic lung disease. AB - The effect of a stress management program on morbidity and psychosocial and physical function in patients with chronic lung disease was assessed. Adults attending either a VA pulmonary clinic or university hospital pulmonary rehabilitation clinic who met criteria for obstructive or restrictive pulmonary disease were randomly assigned to receive the intervention or to a control group. The intervention was provided by a nurse and included one to three teaching sessions, reading material, audiotapes, and telephone follow-up. The program focused on stress management techniques such as cognitive restructuring, progressive relaxation, breathing exercises, and visual imagery. The 45 experimental subjects were similar to the 49 controls with respect to baseline characteristics. Experimental and control subjects had similar rates of mortality, hospital days, bed-disability days, restricted-activity days, and physician visits during the 12-month follow-up. There were no differences between the two groups in physical or psychosocial function at six months or in levels of stressful life changes, social supports, and self-esteem at six and 12 months. Intervention recipients had better function at 12 months, suggesting a possible benefit of the intervention. PMID- 2227173 TI - Local anesthesia for neonatal circumcisions: are family practice residents likely to use it? AB - Dorsal penile nerve block with lidocaine (DPNB) is a local anesthetic technique for neonatal circumcision which is both effective and consistent with ethical concerns for infant welfare. As such, it should be included in training programs that prepare residents to care for newborns. To assess the current level of DPNB use by residents in a family practice training program and to identify attitudes and other factors that relate to use, a survey was sent to 127 residents in the Department of Family Practice and Community Health, University of Minnesota. Of the 101 respondents, 55% had used DPNB, and 17% could be characterized as high users, employing the technique for over one half of the circumcisions they performed. Residents with comprehensive understanding of the newborn's capacity to feel pain were more likely to be using DPNB than their less well-informed counterparts. Four factors were identified as predicting use: cooperation of nursery staff for the procedure, accessibility of instruction in PNB technique, belief that PNB is effective in reducing infant pain, and likelihood of parents giving consent for PNB. These results suggest strategies which may be implemented by family practice educators who wish to promote the principles and techniques of DPNB. PMID- 2227174 TI - Interpreting office radiographs: a research-based curricular prototype for training family practice residents. AB - Radiographic film interpretation is one area of the family practice residency training curriculum that has been given little focused emphasis. Starting with a series of studies into the office practice of radiology by family physicians to define need, content, and interpretation skill level, and following a systematic curriculum design process, the authors developed a comprehensive curriculum for teaching office X-ray interpretation to family practice residents. The final curricular prototype consists of: 1) a complete set of curriculum objectives; 2) a written monograph; 3) a set of instructional X-rays; and 4) a set of evaluation films. This research-based curriculum development process may serve as a model for developing other educational components for family practice residency training. PMID- 2227175 TI - Predicting elderly patients' mobility using fall history and physician assessment. AB - This study tested whether a patient's history of falls or an office clinician's general assessment can predict which ambulatory elderly patients will do poorly on mobility testing. Ambulatory patients making routine visits who were age 65 or older, mentally competent, and not acutely ill were eligible. Fifty-two (91%) of these patients participated by completing a fall history questionnaire and undergoing mobility testing. After the visit, the attending physician estimated how the patient would score on the mobility test. Twelve (23%) of the patients reported falls and seven (13.5%) reported fall injuries in the preceding year. Both fall history and physician estimate of mobility score significantly correlated with the measured mobility score. Only the physician estimate of mobility score, however, had adequate sensitivity (94.4%) and specificity (82.4%) to be clinically useful. This estimate will allow the clinician to selectively apply mobility testing to those patients likely to score poorly. PMID- 2227176 TI - Family practice residents and the elderly: fostering positive attitudes. AB - The population of elderly patients is steadily growing. Because physician attitudes toward caring for elderly patients are often negative, it is important to identify aspects of training that lead to favorable attitudes toward the practice of geriatrics. This study investigated the relationships among past casual experiences, educational experiences, level of training, faculty attitudes, and current resident attitudes. All Louisiana family practice residents (72) and program faculty members (35) were surveyed, with response rates of 69% and 86%, respectively. Residents generally held positive attitudes toward the elderly. Variables associated with positive resident attitudes were the amount of didactic training and faculty attitudes. No differences were found among the attitudes of residents at different levels of training. These findings highlight the importance of cognitive training and role modeling in geriatrics. Educational settings in which training occurs--classrooms, ambulatory care facilities, hospitals, and nursing homes--deserve careful consideration. PMID- 2227178 TI - Risks and benefits of a family systems approach to medical care. AB - The "art of medicine" is struggling for survival in medical education, practice, and research. The authors embrace the biopsychosocial model as an ideal new paradigm for medicine and propose that the family systems approach provides the best available vehicle for applying the biopsychosocial model to everyday medical practice and research. Such an approach would require major changes in the way health care is delivered and offers both benefits and risks for family physicians to consider. One important change would involve the sharing of physicians' power in a health care system that emphasizes collaboration among individuals, families, and a variety of professionals. Such revolutionary changes should be approached with caution. PMID- 2227177 TI - Computerized health information networks: house calls of the future? AB - The Cleveland Free-Net is the nation's first free open-access computer system providing health information to the public. An online survey was developed for the family medicine clinic housed within the Free-Net to study the characteristics of the users of the system and the reason they selected the Free Net as a source of health information. Three areas were addressed: 1) user demographics; 2) content analysis of questions; and 3) reasons Free-Net was used instead of the person's own health care provider. An analysis of the initial system done in 1985 revealed that early users of the system were known to be predominantly white male professionals, generally in the 25-35 age range. In comparison to that profile, more of the users in this study were women, but the majority of users continued to be white male professionals. Questions asked can be classified in six categories: diagnosis, symptoms, treatment, medications, laboratory tests, and prevention. The main categories of medical concerns were cardiovascular, gastrointestinal, obstetrical, and gynecologic problems. Users tended to use the Free-Net for health information rather than their physician because the traditional means was not always appropriate for the life-style of this population. PMID- 2227179 TI - Reprint requests for family medicine literature: how do we respond? AB - Requesting and sending reprints of articles published in the medical literature is an established tradition. This survey of authors of family medicine literature found that 54% believed the tradition should be continued, and 43% felt reprints meet a real need. The authors responded to 90% of the requests. Those authors who paid the cost out of their own pockets were significantly more likely to view reprints as useful and more likely to respond to requests. Support for innovative ways of disseminating information, ways that may meet needs that reprints do not, is potentially available. PMID- 2227180 TI - [Voluntary hypoventilation changes in the breathing pattern of the bradypnea type in healthy nonpregnant women and in normal and complicated pregnancies]. PMID- 2227181 TI - [Spontaneous temperature fluctuations of human hands]. PMID- 2227182 TI - [The characteristics of the kidney functions and water-electrolyte metabolism in children in the Far North]. PMID- 2227183 TI - [Changes in human heat exchange and nutritional status after moving to a region with a hot climate]. PMID- 2227184 TI - [The stability characteristics of the spatial-temporal organization parameters of the EEG in patients with craniocerebral trauma]. PMID- 2227186 TI - [The determination of the structure and significance of the physical status of mine rescuers of different ages and qualifications]. PMID- 2227185 TI - [The hormonal reaction of the healthy subject to combined exposure to the insulin test and physical loading]. PMID- 2227187 TI - [Functional adaptive regulation in operators in gas-chemical production]. PMID- 2227188 TI - [The self-organization of proliferating cellular systems: the basic patterns of interaction, functioning and evolution]. PMID- 2227189 TI - [The dynamic analysis of the functional status of a test subject after 1.5-hour monotonous operator activity]. PMID- 2227190 TI - [Profiles of the neuronal reactions of the human brain during visual testing for orientational sensitivity]. PMID- 2227191 TI - [The correlation between the amount of slow fibers in the musculus vastus externus of the thigh and sports results]. PMID- 2227192 TI - [Shifts in the body thermal status during electrical stimulation of the skeletal muscles]. PMID- 2227194 TI - [A standardized psychophysiological conflict-game test]. PMID- 2227193 TI - [A method for determining the level of information loading in subjects in operator jobs]. PMID- 2227195 TI - [Superslow fluctuations in the indices of the CNS functional status and the rate characteristics of the process of problem solving]. PMID- 2227196 TI - [Electrophysiological research on the functional organization of the human brain during directed attention. III. 11- to 12-year-old children with retarded mental development]. PMID- 2227198 TI - [The functional status of the cardiovascular system in healthy subjects and hypertension patients based on vector electrocardiographic data (biorhythmological research)]. PMID- 2227197 TI - [The dynamic cardiovascular responses to varying levels of loading in patients with ischemic heart disease]. PMID- 2227199 TI - [The effect of information loading and physical activity of differing intensities on the organization of the heart rhythm in children]. PMID- 2227200 TI - [An evaluation of the statistical characteristics of the spatial coherence of bioelectrical processes in the human brain. I. Multiple electroneurographic studies of parkinsonism patients]. PMID- 2227201 TI - [The effect of a local static load on left ventricular contractile function in 6- to 7-year-old children]. PMID- 2227203 TI - [The characteristics of the function of the cardiovascular system in 6- to 7-year old children compared with the type of manual asymmetry]. PMID- 2227202 TI - [The dynamics of the central and cerebral circulations during the head-down tilt test taking into account the individual characteristics of 7- to 10-year-old children]. PMID- 2227204 TI - [A comparison of the ventricular myocardial contractility of newborns and adults by using a noninvasive echocardiographic method]. PMID- 2227205 TI - [The relationships between orthostatic hemodynamic stability and the blood circulatory indices at rest and during physical loading]. PMID- 2227206 TI - [The dynamics of the phase and amplitude indices of the rheopolycardiogram depending on the directed changes in contractility and the load parameters]. PMID- 2227207 TI - [The circadian dynamics of the indices of the human cardiorespiratory system under physical loading and in an altered gaseous environment]. PMID- 2227208 TI - [Seasonal changes in the pulmonary ventilation function and respiratory tract reactivity in healthy subjects]. PMID- 2227209 TI - Qui tam suits: scientific misconduct goes to the jury. PMID- 2227210 TI - Theoretical studies of protein conformation by means of energy computations. AB - In this review we describe fundamental concepts and applications of conformational energy computations, with emphasis on some recent advances and problems being investigated. The formulation of potential energy functions is described, including the nature of the intramolecular force field, the representation of interactions with the solvent, and considerations of entropy contributions. Approaches to the search for the optimal potential energy are summarized. Examples cited among applications of conformational energy computations include refinement of X-ray crystallographic structures, the use of computations in conjunction with NMR data, prediction of the structures of proteins based on either homology or on other procedures that surmount the multiple-minima problem, the analysis of hierarchical levels of structure and assembly, and interactions in enzyme-substrate complexes. PMID- 2227211 TI - Legume lectins--a large family of homologous proteins. AB - More than 70 lectins from leguminous plants belonging to different suborders and tribes have been isolated, mostly from seeds, and characterized to varying degrees. Although they differ in their carbohydrate specificities, they resemble each other in their physicochemical properties. They usually consist of two or four subunits (25-30 kDa), each with one carbohydrate binding site. Interaction with carbohydrates requires tightly bound Ca2+ and Mn2+ (or another transition metal). The primary sequences of more than 15 legume lectins have been established by chemical or molecular genetic techniques. They exhibit remarkable homologies, with a significant number of invariant amino acid residues, among them most of those involved in metal binding. The 3-dimensional structures of the legume lectins are similar, too, and are characterized by a high content of beta sheets and a lack of alpha-helix. The location of the metal and carbohydrate binding sites, established unequivocally in concanavalin A by high resolution X ray crystallography, appears to be the same in the other legume lectins. Several of the lectin genes have been cloned and expressed in heterologous systems. This opens the way for the application of molecular genetics to the investigation of the atomic structure of the carbohydrate binding sites of the lectins, and of the relationship between their structure and biological activity. The new approaches may also provide information on the mechanisms that control gene expression in plants and on the role of lectins in nature. PMID- 2227212 TI - Oncogenes in growth and development. AB - Oncogenes play a major role in the control of proliferation in animal cells. Because the growth of cell populations is regulated by the stimulatory and inhibitory growth factors in the environment, we have attempted in this review to relate the function of oncogenes to the mechanism of action of growth factors. This correlation allows a description of the cell cycle that rests on a molecular basis and in which protooncogenes figure prominently as the cellular messengers of the environmental growth stimuli. PMID- 2227213 TI - Molecular biology and biochemistry of pyruvate dehydrogenase complexes. AB - In most organisms, the pyruvate dehydrogenase complex catalyzes the pivotal irreversible reaction that leads to the consumption of glucose in the aerobic, energy-generating pathways. A combination of biochemical and molecular biology studies have greatly expanded our understanding of the overall structural organization of this multicomponent system, delineated the locations and elucidated the functions of structural domains of the catalytic components, and revealed significant evolutionary changes. Important to this progress was the deduction of the primary amino acid sequences from cDNA clones for each of the catalytic components from several species. The greatest detail is available for the FAD-containing dihydrolipoamide dehydrogenase component, which is the only component for which tertiary structure information has recently emerged. For the dihydrolipoamide acetyltransferase core component, a similar but species-variable multidomain structure is established that is responsible for the distinct architectures of the inner cores, the peripheral binding of the other components, and the conveyance of reaction intermediates between distantly separated active sites. A second lipoyl-bearing component, protein X, has been shown to play a critical role in the organization and function of the complex from many higher organisms. Although much is known about the means of effector modulation of mammalian complex activity, identification of the signal eliciting its regulation by insulin still poses an exciting challenge. PMID- 2227214 TI - Human growth hormone in the blood of athymic mice grafted with cultures of hormone-secreting human keratinocytes. AB - An established line of human epidermal keratinocytes was permanently transformed by transfection with plasmid vectors bearing the human growth hormone gene under the control of two different promoters. Suitable selection permitted the isolation of clones secreting abundant growth hormone in culture. When such cultures were grafted to athymic mice, human growth hormone could be detected in the blood of the mice at concentrations in the physiological range for more than 4 weeks. Retrograde transfer from epithelial cells should be studied further as a possible means of introducing exogenous gene products into the circulation of humans. PMID- 2227215 TI - Protection against cisplatin toxicity by administration of glutathione ester. AB - The role of cellular glutathione in the prevention of toxicity due to the anti cancer drug cisplatin (cis-diamminedichloroplatinum) was explored in mice treated with buthionine sulfoximine (BSO), a selective inhibitor of gamma glutamylcysteine synthetase (and therefore of glutathione synthesis), and with glutathione and glutathione monoisopropyl ester. Pretreatment of mice with BSO enhanced the lethal toxicity of cisplatin by about twofold. Administration of glutathione ester (dose, 2.5-7.5 mmol/kg) protected against lethal cisplatin toxicity; glutathione was also effective, but much less so. Glutathione ester, in contrast to glutathione, is effectively transported into cells and split to glutathione intracellularly. The previous findings that administered glutathione does not protect against lethal toxicity due to cadmium ions and mercuric ions, whereas glutathione ester does, suggest that intracellular glutathione is required for protection against these heavy metal ions. That administration of glutathione has a protective effect on cisplatin toxicity suggests that the toxic effects of cisplatin may be exerted both intracellularly and extracellularly, and that extracellular glutathione (or its degradation products) may form a complex with cisplatin extracellularly. The finding that glutathione ester is more effective than glutathione in protecting against the toxicity of cisplatin suggests that use of glutathione ester may be therapeutically advantageous. PMID- 2227216 TI - Whole-body imaging of the distribution of mercury released from dental fillings into monkey tissues. AB - The fate of mercury (Hg) released from dental "silver" amalgam tooth fillings into human mouth air is uncertain. A previous report about sheep revealed uptake routes and distribution of amalgam Hg among body tissues. The present investigation demonstrates the bodily distribution of amalgam Hg in a monkey whose dentition, diet, feeding regimen, and chewing pattern closely resemble those of humans. When amalgam fillings, which normally contain 50% Hg, are made with a tracer of radioactive 203Hg and then placed into monkey teeth, the isotope appears in high concentration in various organs and tissues within 4 wk. Whole body images of the monkey revealed that the highest levels of Hg were located in the kidney, gastrointestinal tract, and jaw. The dental profession's advocacy of silver amalgam as a stable tooth restorative material is not supported by these findings. PMID- 2227217 TI - The Human Genome Project: answers closer than you think? PMID- 2227218 TI - [Coronary surgery: technical progress in the last decade]. PMID- 2227220 TI - [Analysis of the recovery phase after the ergometric test]. PMID- 2227219 TI - [Myocardial ischemia induced by exercise. Analysis of the recovery phase. Behavior of the rate-pressure normalization product in patients with fixed ischemic threshold and patients with variable ischemic threshold]. AB - Traditionally, in patients with exercise-induced myocardial ischemia we analyze the stress-test by studying the behaviour of double product at ischemia. We recognize the presence of a functional component in the reduction of coronary flow reserve if the double product at ischemia (DPI) varies in 3 stress-tests i.e. more than 20% or more than 3200 mmHg b m'-1. Any analysis that relies exclusively on double product at ischemia is, of necessity, limited to the beginning of the ischemic phenomenon. To better understand the development of the whole event, we also considered the double product calculated when the ischemic electrocardiographic signal regressed (double product of normalization: DPN). More specifically, we set out to determine whether or not double product at ischemia behaviour in patients with variable ischemic threshold (i.e. double product at ischemia variation greater than 3200 mmHg b m'-1) differs from that of patients with fixed ischemic threshold (i.e. double product at ischemia variation less than b m'-1). We performed four multistage bicycle ergometer tests, without drugs, on 19 patients with chronic exertional anginal and exercise-induced ST depression. Patients were tested at the same time of day, within a 10 day period. In the second, third and fourth stress test double product at ischemia was calculated. On the basis of double product at ischemia values in three stress tests, we distinguished two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227221 TI - [Nisoldipine in the therapy of stable exercise angina: evaluation of its efficacy in ergometric tests compared with propranolol]. AB - The safety and efficacy of a new dihydropyridine calcium antagonist, nisoldipine, were studied in comparison with propranolol, in patients with stable angina. Following 2 weeks of wash-out of the current therapy and 1 week of placebo, 26 patients underwent two cycloergometer tests, before and 2 hours after placebo administration. Subsequently, 10 mg of nisoldipine twice daily or 40 mg of propranolol three times daily were administered over a 4 week period, in a randomized single-blind fashion. Cycloergometer tests were performed after 2 and 4 weeks, before and two hours after drug administration. Two patients, one out of the nisoldipine group and one out of the propranolol, were considered drop outs. Statistical analysis of the results was performed using two-way variance analysis. With both drugs, time to 1 mm exercise induced ST-segment depression (p less than 0.01), time to angina (p less than 0.01), and exercise tolerance (p less than 0.01) improved furthermore, ST-segment and heart rate recovery time decreased (p less than 0.01). Rate-pressure product values at ischemic threshold and at peak exercise remained unchanged with nisoldipine, while significant reductions were observed with propranolol (p less than 0.01). Maximum ST-segment depression was reduced (p less than 0.01) with both drugs and a further improvement was observed two hours after drug administration (p less than 0.05). At submaximum work-load, rate pressure product values and ST-segment depression were improved with both drugs (p less than 0.01); this improvement was more evident two hours after drug administration. No significant side effects were observed with either drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227222 TI - [Efficacy and duration of effect of two delayed-action preparations of gallopamil in patients with exercise angina]. AB - In 15 subjects (13 male, 2 female) with reproducible threshold ischaemic effort angina, the efficacy and the duration of the effect of two different formulations of gallopamil in equal doses were evaluated. One of these was gallopamil slow release administered twice daily (at 7.00 a.m. and 6.00 p.m.) in doses of 100 mg. The other was action gallopamil immediate release administered four times daily (at 7.00 a.m., 1.00 p.m., 6.00 p.m., 11.00 p.m.) in doses of 50 mg. The double blind study followed the cross-over model. After one week of run-in with placebo and two-weeks of treatment with active preparations, the patients underwent a clinical examination, an ambulatory electrocardiogram monitoring for 24 hours and two cycloergometric effort tests. The ergometric tests were carried out at 10.00 a.m. and at 5.00 p.m. on the same day so that there was a three-hour interval between the administration of both preparations (slow release and immediate release) and the morning test. The ergometric test which was carried out at 5.00 p.m. was at a ten-hour interval from the administration of slow release and at a four-hour interval from the administration of immediate release. For each period of treatment the gallopamil plasma concentrations were dosed during the ergometric test. In both these tests, the two preparations significantly increased the duration of the exercise compared to the basal values with placebo (7.9 +/- 2.3 minutes with placebo, 9.2 +/- 2.0 minutes with slow release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227223 TI - [Clinical and prognostic value of evaluation of atrial vulnerability in an electrophysiological endocavitary and transesophageal study]. AB - Atrial fibrillation or flutter is frequently inducible during endocavitary or transesophageal electrophysiologic study. However, its clinic and prognostic significance has not yet been clarified. We studied 443 patients: 276 underwent endocavitary electrophysiologic study, 228 underwent transesophageal electrophysiologic study and 61 underwent both methods. In 343 of them a satisfactory echocardiogram was obtained. Patients were divided in three groups: gr. I, 93 patients with documented episodes of paroxysmal atrial fibrillation or flutter; gr. II, 257 patients with or without heart disease without clinical atrial fibrillation or flutter; gr. III, 93 symptomatic or asymptomatic Wolff Parkinson-White patients without clinical atrial fibrillation or flutter. Gr. I included patients without overt heart disease (20), with WPW (11), mitral valve prolapse (4), and miscellaneous (58). Gr. II included patients without overt heart disease (49), with concealed Kent bundles (7), Mahaim (1) or James fibers (1) mitral valve prolapse (6), sick sinus syndrome (40), miscellaneous (91), or syncope of an unknown origin (62). Atrial vulnerability was evaluated both by endocavitary and transesophageal electrophysiologic study using two different protocols; the first protocol was moderately aggressive (prot. A), while the second was aggressive (prot. B). Endocavitary electrophysiologic study. Prot. A: single and double extrastimuli at the three heart rates (sinus, 100 and 150/m'), 10/m' incremental atrial pacing from 160 to 250/m; prot. B: prot. A + incremental atrial pacing from 260/m' up to 2:1 St-A block. Transesophageal electrophysiologic study. Prot. A: 10" atrial burst at 100-600/m' prot. B: prot. A + 6-9" increasing rate bursts from 200 to 800/m'. End point of all protocols: initiation of greater than 1' atrial fibrillation or atrial flutter. RESULTS: Endocavitary electrophysiologic study. A greater than 1' atrial fibrillation or atrial flutter was induced with the two protocols respectively in 67% (52/78) and 85% (51/60) of gr. I, in 17% (26/150) and 36% (38/105) of gr. II and in 35% (17/48) and 44% (21/48) of gr. III (gr. I vs gr. II p less than 0.001 for prot. A and p less than 0.01 for prot. B; gr. II vs gr. III p less than 0.001 for prot. A and NS for prot. B). Induced atrial fibrillation or atrial flutter using the two protocols had a greater than 5' duration respectively in 83 and 78% of gr. I, 62 and 42% of gr. II and in 41 and 38% of gr. III.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2227224 TI - Electropharmacological test with pentisomide (CM 7857) in patients with sustained ventricular tachycardia. AB - Pentisomide (CM 7857) is a new class I antiarrhythmic drug whose effect on sustained ventricular tachycardia has only been slightly investigated to date. The aim of this paper is to examine the pentisomide action on selected patients with ventricular tachycardia inducible during intracavitary electrophysiological study. Thus, 12 patients (9 M, 3 F, mean age: 45.2 years, range: 24-78), all but two with detectable heart disease, underwent electropharmacological tests with pentisomide after they had resulted "non responders" (8 patients) or had had a proarrhythmic worsening effect (3 patients) to electropharmacological tests with amiodarone or flecainide or propafenone or mexiletine. After the inducibility and the reproducibility of ventricular tachycardia has been assessed in the basal state, all patients underwent several attempts to reinduce ventricular tachycardia, during the i.v. infusion of pentisomide 1.5 mg/kg/5 min followed by continuous infusion of 1 mg/kg/h, at the same time drug plasma level was assessed. Ventricular tachycardia inducibility was still inducible after pentisomide, but with a longer cycle length (446 +/- 88 versus 337 +/- 82 msec) than in the basal state (p less than 0.0025). No patients had proarrhythmic worsening effects. The pentisomide plasma level (available in 5 patients) ranged from 3.4 to 22.3 (mean 8.9 micrograms/ml). Four patients underwent chronic oral treatment (in 1 pt in association with amiodarone) with a good clinical outcome (mean follow-up 6.25 months, range 1-12). We stress the absence of proarrhythmic worsening effects and the powerful effect of the drug on ventricular tachycardia cycle length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227225 TI - Late potentials in idiopathic dilated cardiomyopathy. AB - Twenty-five patients with idiopathic dilated cardiomiopathy were investigated in order to evaluate the role of late ventricular potentials as possible markers of ventricular tachycardia or sudden cardiac death. Holter monitoring showed ventricular tachycardia in 9 patients (group A) all of whom had late ventricular potentials, (mean +/- SD length 37.22 +/- 15.83 ms and mean +/- SD voltage 5.62 +/- 2.78 microV). Mean +/- SD ejection fraction in this group was 20 +/- 9.39%. In 16 patients (group B), without ventricular tachycardia, means +/- SD ejection fraction 27.5 +/- 8.17%; late ventricular potentials were recorded in 2 patients. During the follow-up period (means +/- SD 11.53 +/- 7.19 months), 3 patients underwent heart transplantation, 2 patients underwent pace-maker implantation and 2 patients from the ventricular tachycardia group died one from sudden cardiac death and the other from progressive heart failure. No significant differences were found in the ejection fraction either between the ventricular tachycardia and the non-ventricular tachycardia group, or between the late ventricular potentials and the non-late ventricular potential groups. Negative data were also obtained when we tried to find a correlation between the ejection fraction and late ventricular potential length and/or voltage. Good results were observed with regard to sensitivity (100%), specificity (87%) and predictive accuracy (81%) but follow-up data did not specify a definite prognostic value for late ventricular potentials. The Authors conclude that late ventricular potentials are markers of patients with idiopathic dilated cardiomyopathy who are prone to ventricular tachycardia. However, the role of late ventricular potentials in sudden cardiac death is still uncertain. PMID- 2227226 TI - [Right ventricular dysplasia and sudden death in young people]. AB - In this study two autoptic cases of right ventricular dysplasia, observed in young and asymptomatic subjects who died suddenly are reported. In these patients, the "primary" myocardial atrophy involved the right ventricle, the right atrium and the conduction system: the sinoatrial node and the internodal pathways (in both cases) and the hisian bifurcation (only in the second case). The primary ventricular dysplasia was always associated with "secondary" transmural hyperplasia of the sub-epicardial fat tissue except for the anterior wall of the pulmonary infundibulum. According to the findings observed, we think that: 1) in all cases of right ventricular dysplasia a careful examination of the conduction system must be performed due to the fact that the lethal arrhythmias can be not only "hyperkinetic" but also "hypokinetic" arrhythmias; 2) right ventricular dysplasia is a dysplastic-congenital disease and transmural fatty hyperplasia depends both on "primary" myocardial atrophy and on the presence of sub-epicardial fat tissue; the latter is related to the age of the patient. PMID- 2227227 TI - [Arrhythmogenic dysplasia or cardiomyopathy?]. PMID- 2227228 TI - [Mexiletine in patients with progressive infarction and reduced ventricular function: anti-arrhythmic efficacy and hemodynamic effects]. AB - Reduced left ventricular function and ventricular arrhythmias are the main risk factors associated with sudden death in patients with previous acute myocardial infarction. Antiarrhythmic therapy may have side-effects on myocardial contractility and sometimes makes the arrhythmia itself worse, especially when the pump function is seriously compromised. The aim of this study was to evaluate the efficacy of oral mexiletine as well as any modifications in left ventricular function by means of ambulatory ECG monitoring and angiocardiography with Tc 99m, at rest and after the handgrip test, in 20 patients with previous myocardial infarction and ventricular arrhythmias who were grouped into NYHA class II and class III. The mexiletine therapy lasted three weeks. Both classes showed a significant decrease in the number of ventricular extrasystoles/hour and in the number of couples (p less than 0.01). The decrease in the number of the ventricular runs proved to be higher in the general analysis (p less than 0.01) than in each NYHA class (p less than 0.05). At the end of the study, significant modifications were not observed either in the end-diastolic and end-systolic volumes, or in the ventricular ejection fraction. PMID- 2227229 TI - [The role of surgery and percutaneous valvuloplasty in conservative treatment of post-rheumatic mitral stenosis]. PMID- 2227230 TI - [The conclusion of the trial of the Italian group in Second International Study of Infarct Survival]. PMID- 2227231 TI - The autopsy registry of congenital heart disease at the University of Padua. PMID- 2227232 TI - [Incidence of inflammatory bowel disease in the Nord-Pas-de-Calais region and the Somme area of France in 1988]. AB - No epidemiological data on inflammatory bowel disease (IBD) are available in France. We therefore conducted a prospective epidemiologic study of IBD in the Nord-Pas de Calais region and the Somme department of France (4.5 million inhabitants). Each suspected new case was reported by all (private and public) gastroenterologists (n = 120) and a questionnaire was filled out at the gastroenterologist office by an epidemiologist. The final diagnosis of Crohn's disease (CD), ulcerative colitis (UC), or proctitis (UP) was made in a blind manner by two gastroenterologists. During 1988, 576 IBD patients were identified; 281 (49 percent) had CD, 207 (36 percent) had UC including 75 UP; and 88 (15 percent) had unclassified colitis. The incidence rate per 10(5) was 6.3 for CD and 4.6 for UC. The female/male ratio was 1.4 for CD and 0.9 for UC. The mean age at the time of diagnosis was 31 years for CD and 40.5 years for UC. The mean time between onset of symptoms and diagnosis was longer for CD (15 months) than for UC (6.8 months). These preliminary data suggest that the incidence of IBD is high in Northwestern France and comparable, for CD, to the highest incidence of Northern Europe. PMID- 2227233 TI - [Local recurrence of rectal cancers. Multidimensional analysis by anatomoclinical factors and role of irradiation]. AB - Pre- or postoperative radiation therapy reduces the incidence of local recurrence after surgical treatment of rectal carcinoma. Factors related to local recurrence were analyzed retrospectively by uni- and multivariate analysis. One hundred and fifty-five patients (mean age: 65 years) were operated on with curative intent between 1967 and 1984. Ninety-four patients (46 patients having abdominoperineal resections (APR), and 48 having anterior resections) did not receive radiation therapy. Sixty-one patients had preoperative radiation therapy followed by APR in 59 cases. Univariate analysis showed that the risk of local recurrence increased significantly with male sex (p less than 0.006), positive lymph nodes (p less than 0.01), vascular invasion (p less than 0.02), and Astler-Coller classification (p less than 0.05). Tumor located at less than 5 cm from the anal verge was significantly related to recurrence only in patients not receiving radiation therapy (p less than 0.02). Multivariate analysis including therapeutic modalities showed that local recurrence was significantly related with male sex (p less than 0.02), positive lymph nodes (p less than 0.01), and distance to anal verge (p less than 0.01). The beneficial role of radiation therapy appeared only for tumors located 5 cm or less from the anal verge. Prognostic scores were established using these variables and the effect of irradiation was evaluated according to these scores. Radiation therapy significatively reduced the risk of local recurrence in low-risk patients, i.e., female with low-lying tumor and with negative lymph nodes (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227234 TI - [Primitive digestive localizations of malignant non-Hodgkin's lymphoma. Prognostic factors of locally advanced disease: stage II. Report of 67 cases]. AB - Sixty-seven patients with non-Hodgkin's lymphoma of the digestive tract with locally advanced disease (stage II) were analyzed to determine the main factors influencing survival. There were 19 patients with stage II E1 and 48 with stage II E2 disease (Musshoff classification). According to the Kiel classification, 46 percent were low grade, 46 percent were high grade, and 8 percent were unclassified. The principal sites involved included the stomach: 11 cases, small intestine: 21 cases, colon: 12 cases, and mesentery: 11 cases. Lymphoma was unique in 45 cases (67 percent). Treatment consisted of laparotomy in 61 of 67 cases: partial resection was achieved in 21 cases, complete resection in 27 cases, and exploration only in 13 cases. Chemotherapy, according to histopathological subtypes, was employed in 90 percent of cases. Radiation therapy was applied in 25 patients (37 percent), essentially when there was residual disease after surgery (17 patients). Therapeutic indications were dependent on histological subtype, extension, and the therapy regimen in use at the time of treatment. Five patients were treated by surgery only, 2 by surgery and radiation therapy, 37 by surgery followed by chemotherapy, and 23 by all three treatment modalities. Overall survival was 62 percent at 5 years. Univariate analysis showed that 5-year survival rates were not influenced by sex, age, histopathological subtype (low grade: 69 percent; high grade: 59 percent; NS) or local extension (stage II E1: 76 percent vs stage II E2: 59 percent; NS). In contrast, complete surgical excision (p = 0.06) and radiation therapy in case of local residual disease (p = 0.02) seemed to improve survival. The main prognostic factor was the achievement of a complete therapeutic response (CR) (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227236 TI - [Should we still prescribe intravenous cholangiography?]. PMID- 2227237 TI - [Intravenous cholangiography is not indicated before cholecystectomy for uncomplicated lithiasis]. AB - The purpose of this prospective study was to assess the usefulness of intravenous cholangiograms before elective cholecystectomy for lithiasis. The accuracy of preoperative intravenous cholangiography to detect choledocolithiasis was compared with that of routine operative cholangiography. All patients had preoperative intravenous cholangiography provided that they did not have known common bile duct gallstones or a previous history of adverse reaction to iodine. As well, patients presenting with cholestasis, cholecystitis or cholangitis were excluded. A choledocotomy was performed when the operative cholangiography disclosed choledocolithiasis; the preoperative intravenous cholangiograms were shown to the surgeon only after the operation. One hundred patients were selected among 206 consecutive operations for biliary lithiasis. A choledocolithiasis was detected in 3 preoperative and in 9 operative cholangiographies. Twelve choledocotomies were performed: one or more stones (1 to 12) were found in 9 patients; operative cholangiography was accurate in all these cases whereas preoperative cholangiography was accurate in only 2 (sensitivity = 22 percent). We conclude that preoperative cholangiography is useless before elective cholecystectomy for lithiasis and is unreliable to select patients in which operative cholangiography could be omitted. PMID- 2227235 TI - [Digestive gas: pathophysiology and therapeutic approach in functional bowel disorders]. PMID- 2227239 TI - [Family screening strategy for genetic hemochromatosis]. PMID- 2227238 TI - [Thermic and metabolic effects of meals in liver cirrhosis assessment of oxidation and storage rates of nutrients]. AB - The thermic effect of food was evaluated in 10 cirrhotic patients and 7 normal controls by indirect calorimetry during 6 hours following intake of a mixed meal supplying 15 kcal/kg of body weight and containing 30, 15 and 55 percent as lipid, protein and carbohydrate calories respectively. The rates of storage and oxidation of nutriments, as well as variations of blood glucose, insulin, plasma lactates, free fatty acids, glycerol, and ketonic corps were also evaluated. The thermogenic response to food was lower (p less than 0.025) and delayed in cirrhotic patients. In cirrhotic patients the rate of glucose oxidation was significantly increased (70.2 +/- 3.9 vs 50.4 +/- 3.9 percent of the glucose load; p less than 0.01) suggesting a defect in glycogen storage. These results can be related to insulin resistance as attested by a larger increase of glucose and insulin levels in cirrhotics than in controls (p less than 0.001 and p less than 0.001, respectively). Compared with controls, lipolysis in cirrhotic patients was more suppressed as shown by a sharper decrease of free fatty acids and glycerol levels (p less than 0.001 and p less than 0.02, respectively). Furthermore, the rate of lipid oxidation decreased more in cirrhotic as compared with controls (p less than 0.001) before becoming completely suppressed. De novo lipogenesis appeared between the 2nd and 4th hours. Consequently, the rate of lipid oxidation was significantly reduced in cirrhotic vs controls (14.3 +/- 5.0 vs 30.5 +/- 3.7 percent of the lipid load; p less than 0.02) showing an increased rate of lipid storage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227240 TI - [Salmonella pancreatic abscess. Treatment by drainage without cholecystectomy]. AB - We report a case of necrotic collection in the head of the pancreas infected by Salmonella typhimurium. Treatment associated necrosectomy and antibiotic therapy without cholecystectomy. The course of pancreatic disease was uneventful. Complete sterilization was obtained with quinolone antibiotic therapy. PMID- 2227241 TI - [Primary adenocarcinoma of the ileostomy after total proctocolectomy for ulcerative colitis]. AB - A 61-year-old man developed primary adenocarcinoma with skin invasion, at the ileostomy site 33 years after a proctocolectomy for ulcerative colitis. A total of eleven patients with ileostomy adenocarcinoma have been reported in the literature. Ten patients were treated surgically for ulcerative colitis and the other for adenomatous polyposis coli. The diagnosis of stomal malignancy was made 9 to 36 years after the ileostomy (mean interval, 22 years). The pathogenesis of the malignant growth is uncertain and several possibilities are discussed: stasis, severe chronic inflammation, colonic metaplasia and severe dysplasia of the ileal mucosa. When an ileostomy requires late revision for inflammatory changes, careful pathologic examination of the entire stoma and surrounding skin is essential. PMID- 2227243 TI - Production of paf-acether by various bacterial strains. PMID- 2227242 TI - [Unusual cause of ascites: the POEMS syndrome]. AB - A 39-year-old woman presented with polyneuropathy, hepatomegaly, splenomegaly, endocrinopathy, monoclonal protein and skin changes, several of the many clinical features of the recently described POEMS syndrome. In addition, she had a Castleman's disease (angiofollicular lymph node hyperplasia). In this case ascites was a main presenting feature. Thus, the POEMS syndrome must be added to the list of rare causes of ascites. Electron microscopy of the liver showed perisinusoidal fibrosis. PMID- 2227244 TI - [Possibility of prednisone-omeprazole interference in bullous pemphigoid]. PMID- 2227245 TI - [Serum piperacillin pharmacokinetics in ascitic cirrhosis]. PMID- 2227246 TI - [Tumoral seeding after percutaneous liver biopsy of colonic metastasis]. PMID- 2227247 TI - Effects of endoscopic variceal sclerotherapy using GT XIII on blood coagulation tests and the renal kallikrein-kinin system. AB - Forty-six sclerotherapy sessions were performed on liver cirrhotics with high risk esophageal varices using GT XIII, a sclerosant composed of gelatin, thrombin and coagulation factor XIII. GT XIII was effective for the prevention of temporary symptoms and transient hypotension observed in 55 sclerotherapy sessions using thrombin. In 42 (91%) sessions, patients underwent sclerotherapy with no symptoms, and in the other four (9%) sessions, only slight symptoms of general fatigue and headache were observed. Changes in the mean arterial pressure were significantly smaller in sessions using GT XIII than in those using thrombin (-12.3 +/- 13.6 vs. -26.8 +/- 20.7 mmHg, P less than 0.01). Changes in coagulation tests, similar to those of disseminated intravascular coagulation (DIC), were also reduced in sessions using GT XIII. Urinary kallikrein and kinin excretion significantly increased after the procedure (P less than 0.01), indicating activation of the renal kallikrein-kinin system. Increases in urinary kallikrein and kinin excretion showed a significant relationship with the consumed plasma fibrinogen levels (r = -0.51, P less than 0.01 and r = -0.58, P less than 0.01, respectively), and it was suggested that activation of the glandular kallikrein-kinin system caused by abrupt DIC-like changes in the hemostatic system might play a role in manifestations of temporary complications occurring with the use of hemostatic agents containing thrombin. PMID- 2227248 TI - The relationship between interdigestive gallbladder and gastroduodenal motility in man. AB - The relationship between interdigestive gallbladder and gastroduodenal motility simultaneously with the behavior of plasma motilin and CCK levels in 20 subjects was investigated. We used an infusion catheter method for the measurement of gastroduodenal motility, and real-time ultrasonography for the measurement of gallbladder size. In gastric phase II, the gallbladder contracted with extension of the major axis and shrinking of the minor axis, with its minimum volume being 84% of the volume in phase I. The gallbladder then filled rapidly assuming a sphere-like shape with extension of the minor axis and shrinking of the major axis in gastric phase I. This motility was recognized only during the gastrointestinal interdigestive migrating complex (GI-IMC) cycle, originating in the stomach, and was associated with an increase of motilin levels, it was not seen before or after the intestinal IMC (I-IMC), which originated in the duodenum without contraction of the stomach or an increase of motilin levels. Furthermore no apparent relationship was recognized between CCK and gastric or gallbladder motility. Our findings suggest that gallbladder motility in the interdigestive period has a close relationship with gastroduodenal motility and is related to the appearance of the GI-IMC. PMID- 2227249 TI - Class II (HLA-DR, -DP, and -DO) antigens on intestinal epithelia in ulcerative colitis, Crohn's disease, colorectal cancer and normal small intestine. AB - Class II antigens in involved colonic epithelia of ulcerative colitis (UC), Crohn's disease (CD), colorectal cancer, and epithelia of normal small intestine were investigated using an immunoperoxidase method. Ten normal colonic mucosa served as normal controls. Ten specimens were studied for each group. Normal colonic epithelia did not express class II antigens. In colonic diseases; (1) with regard to the frequency and extent of class II antigens on epithelia. HLA-DR antigens were the most highly and greatly expressed, followed by HLA-DP and then HLA-DQ antigens. (2) The extent of HLA-DR and -DP, but not HLA-DQ, expression on epithelia of UC and colorectal cancer seemed to be positively correlated with the degree of mononuclear cell infiltration in the lesion. (3) The extent of class II antigen expression on colonic epithelia in CD was not related to the degree of mononuclear cell infiltration in the lesion. (4) The extent of HLA-DR and -DP expression on epithelia of colorectal cancer seemed to be positively correlated with increasing undifferentiation. In the normal small intestine, where HLA-DR antigens were physiologically expressed on epithelia. HLA-DQ antigens were not expressed. The heterogeneity among colonic diseases, and between the physiological and pathological status, may reflect differences in immunoregulation. PMID- 2227250 TI - Frequency of concurrence of hepatitis B surface antigen and antibody in a large number of carriers in Okinawa, Japan. AB - A large number of chronic hepatitis B surface antigen (HBsAg) carriers in Okinawa, Japan were tested for antibody to HBsAg (anti-HBs), by both radioimmunoassay and enzyme immunoassay methods. Concurrence of HBsAg and anti HBs was found in 166 (26.1%). We found no clear predominance of either liver damage or hepatitis B e antigen (HBeAg) in the concurrent carriers studied. Antibody to pre-S2 antigen (anti-pre-S2) was detected in 16 (9.6%) of 166 subjects with concurrent markers, 15 of these 16 carriers were positive for antibody to HBeAg (anti-HBe). Anti-pre-S2 was correlated with anti-HBe rather than with anti-HBs. The distribution of HBsAg subtypes among carriers determined to have subtypes was 76.7% adw, 22.0% adr, 0.2% ayr, 0.9% adwr, and 0.2% adyr. The distribution of anti-HBs subtypes among concurrent carriers was 51.5% anti-r, 21.4% anti-w, 15.5% anti-d, and 10.7% anti-y. Concurrent carriers had HBsAg of one subtype and heterotypic anti-HBs. Because the HBsAg subtype ay is rare in this area, it is hard to believe that the concurrent carriers with anti-y were infected with hepatitis B virus of which the HBsAg subtype was ay. A dual infection was highly unlikely. It seems that some of the concurrent carriers correlate with compound subtypes adwr and adyr. PMID- 2227251 TI - Serous cystadenoma of the pancreas: radiologic and clinicopathologic features in seven cases. AB - Clinical charts, radiologic features, macroscopic and microscopic findings, and clinical follow-up data in seven patients with serous cystadenoma of the pancreas (SCAP) were retrospectively reviewed. The seven patients with SCAP consisted of six women and one man, and their ages ranged from 52 to 76 years with a mean age of 64.9. The most common symptoms were abdominal mass or pain. The greatest diameter of the seven tumors ranged from 2cm to 10cm with a mean diameter of 6.6cm. On ultrasonograms and/or computed tomograms, the tumors were visualized as lobulated masses containing numerous small cysts. Three tumors angiographically examined were all characteristic hypervascular masses with neovascularity. Macroscopically, the tumors were well-defined lobulated masses containing many cysts with a central scar. Microscopically the cysts were lined with a layer of cuboidal epithelium with centrally placed round nuclei and clear cytoplasms containing abundant glycogen. One patient had undergone a cystojejunostomy five years before the complete resection and the tumor increased in size necessitating a pancreatoduodenectomy. The seven patients with SCAP were doing well without any signs of local recurrence or distant metastasis during the period from 2 months to 120 months after a complete resection. Despite its enormous size at the time of diagnosis, SCAP should be resected with aggressive intent because the complete resection produces a favorable clinical course. PMID- 2227252 TI - Effect of dimethadione derived from repeated oral administration of trimethadione on pancreatic secretion in dogs. AB - The effect of the weak organic acid of dimethadione (DMO) on secretin-stimulated pancreatic secretion was studied with repeated oral administration of trimethadione (TMO), the precursor of DMO, to dogs at a dose of 10 to 160mg/kg/day for a period of 14 days. The bicarbonate concentration in pancreatic juice at a steady state decreased significantly, reflecting a close correlation with the dose of TMO and DMO concentrations in plasma and pancreatic juice. The maximal decrement from the control of cases of no TMO administration was 18.8 mEq/l (12.1% of the control level). The chloride concentration in pancreatic juice showed a reciprocal relation to the bicarbonate concentration. The sum of both anion concentration was constant, irrespective of the dose of TMO. The average carbon dioxide tension of pancreatic juice in all doses of TMO was lower than that of the control, but differences were not statistically significant. The pH, flow rate, sodium and potassium concentrations in pancreatic juice at a steady state did not differ significantly in relation to the dose of TMO. These findings suggest that repeated oral administration of TMO cause a significant decrease in bicarbonate concentration in pancreatic juice, resulting probably from the buffer action of bicarbonate on protons provided from the undissociated form of DMO. PMID- 2227253 TI - Clear and colorless fluid observed during percutaneous transhepatic gallbladder drainage. AB - Twelve patients with discharge of clear colorless fluid during percutaneous transhepatic gallbladder drainage (PTGBD) were encountered during a period of 4.5 years. On the average, the fluid appeared on the 12th day after PTGBD and continued to flow until the completion of observation. The volume was usually less than 60ml per day. It flowed in an alternating pattern with normal yellow color bile each day. The fluid was observed in patients in whom satisfactory patency of the biliary system was confirmed by cholangiography and/or cholangio fiberscopy. Biochemical examinations of the fluid revealed lower biliary lipids but a similar electrolyte composition compared to bile of normal color. It was alkaline. These observations indicate that the clear colorless fluid is different from what is known as "white bile", which is produced when there is an obstruction of the biliary tree. The fluid may be secreted from the gallbladder epithelium or the bile duct epithelium. The significance was not clarified in this study. Further investigation is necessary to elucidate the clinical implications of the clear and colorless fluid secretion. PMID- 2227254 TI - A case of coexisting malignant carcinoid tumor and adenocarcinoma in the papilla of Vater. AB - A 47-year-old Japanese woman in whom obstructive jaundice had already been diagnosed, was found to have a dome-shaped elevated tumor approximately 3 cm in diameter located in the area very close to the papilla of Vater on endoscopical and radiographical investigations. Histopathologically, the resected tumor was composed mainly of solid nests of atypical argyrophilic cells, and partially of an area of well differentiated tubular adenocarcinoma, showing mutual transition in the mucosal layer. Both immunohistochemical and ultrastructural analyses confirmed the difference in character of tumor cells between these two areas: neuroendocrine cell carcinoma and tubular adenocarcinoma of common type in the intestine. To the best of our knowledge, this is only the third case reported to be a coexisting malignant carcinoid tumor and adenocarcinoma arising in the periampullary region. PMID- 2227255 TI - A clinicopathological study of asymptomatic primary biliary cirrhosis in three aged patients. AB - The 3 cases suffering from asymptomatic primary biliary cirrhosis (aPBC) were all older than 70 and female. Case 1, 2 and 3 were respectively 77, 72 and 70 years old. The final diagnosis was made on the basis of clinical observation and liver biopsy. Case 1 was diagnosed as CAH-PBC mixed type from histological findings and classified as stage II-III according to Scheuer's classification. Case 2 was stage I and exhibited morphological features of PBC with arteriosclerotic change. Case 3 was stage I and had dysplasia-like large nuclei in some hepatic cells. Clinically, all cases were AMA positive. Elevation of serum ALP and IgM values was recognized in 2 cases, but serum transaminase and ALP values were not elevated in Case 2 for 1 year. In the follow-up observation during 5 years. Case 1 remained asymptomatic except for gradual elevation of serum ALP value. AMA, which was positive at the time of diagnosis, is now negative after 5 years, but now produces high potency ANA. The incidence of PBC in those aged older than 70 in Japan accounts for only 2-3% of all PBC cases. According to some reports, the prognosis of PBC deteriorates with age. In 3 cases reported here, however, the clinical course did not deteriorate even in untreated cases. This suggests the possibility that some aPBC cases diagnosed at an age older than 70 may have a favorable prognosis. PMID- 2227256 TI - A case of idiopathic portal hypertension after renal transplantation. AB - A case of idiopathic portal hypertension (IPH) developing after renal transplantation is reported. A 33-year-old Japanese male who had undergone renal transplantation 8 years previously was transferred to our hospital because of hematemesis from ruptured esophageal varices. He had no history of any liver disease before the renal transplantation, but had a history of receiving blood transfusion. Abdominal computed tomography (CT) and ultrasonography revealed marked splenomegaly and collateral channels, but no obliteration which might cause portal hypertension in the hepatic or portal vein. No findings suggestive of hepatitis or liver cirrhosis were found either macroscopically on laparoscopy or by liver biopsy. Light microscopic study of the liver biopsy specimen showed mild periportal fibrosis, inconspicuous portal branches in the most peripheral tracts, but no pseudolobule formation or piecemeal necrosis. However collagen deposition was found in the perisinusoidal space and partly in intercellular space on electron microscopy. We consider that the development of portal hypertension in this case is responsible for the collagen deposition, which may be related to the administration of azathioprine after renal transplantation. There are few reports on IPH after renal transplantation, and it is stressed that a lower amount of azathioprine than previously reported may induce IPH under such conditions. PMID- 2227257 TI - An ultrastructural analysis of changes in surface architecture of intestinal mucosa following Giardia lamblia infection in mice. AB - The oral inoculation of Giardia lamblia trophozoites (Portland 1 strain) resulted in the establishment of infection by day 3-5 in NMRI mice. By 9-11 days postinfection, the trophozoites load reached maximum (acute phase) and later declined by day 17-21. The tissue sections from infected animals during the establishment phase of infection indicated limited changes in surface epithelium with normal villous length. Although trophozoites of G. lamblia were seen in all sections lying free in the lumen as discrete parasite, the active invasion by the parasite could not be demonstrated. During the acute phase of infection, fuzzy appearance of brush border, marked reduction in villous height and infiltration of intraepithelial lymphocytes were commonly seen in all tissues. Electron microscopic observation demonstrated large numbers of trophozoites of G. lamblia preferentially aggregated at the base of the villi. At some sites, adhesive marks indicating attachment of Giardia trophozoites were also seen by scanning electron microscopy. In addition, severe flattening and blunting of microvilli and occasional loss of basic morphology of intracellular organelles of columnar cells were noticed at the site of parasite colonization under electron microscopy. The brush border microvilli were noted to be damaged in areas where parasites were attached to surface epithelium with the help of suction discs. The morphological changes associated with Giardia infection tended to reverse as the parasite load declined by day 17-21. Thus we feel that malabsorption in giardiasis with total or varying degrees of morphological alterations of surface mucosa can be explained on the basis of reduced absorptive surface area. PMID- 2227258 TI - Transendoscopic projectile drug delivery. PMID- 2227259 TI - Prostaglandin production by isolated Kupffer cells. PMID- 2227260 TI - Changes of bile bilirubin composition after intravenous bilirubin injection in dogs. PMID- 2227261 TI - Organization of the X gene region of the hepatitis B virus genome. AB - In the hepatitis B virus (HBV) genome four long open reading frames (ORFs) have been found that encode the virus core, surface and polymerase proteins as well as a protein that appears to be involved in virus gene expression (X). However, all HBV genomes examined contain two addition ORFs designated ORF5 and ORF6. ORF5 is located on the same strand as the four known viral genes and is 70-100 codons in size. ORF6 is located on the DNA strand complementary to the one that encodes the other virus genes, and is approximately 210 codons in length. Both ORFs are located in the X gene region which corresponds to the 3' terminus of the linear RNA genome. Northern blot analysis identified an X region specific transcript of approximately 0.7 kb. Although this transcript may be the template for the translation of the X gene protein it may also be involved in the expression of the protein encoded by ORF5. The promoter for this transcript may consist, in part, of the 15 residue sequence GCYTGYYTTGCYCGC because this sequence is near the 5' end of the transcript, it is highly conserved among hepadnaviruses, and it contains sequences involved in RNA polymerase binding. Also, the nucleotides within this region of the hepadnavirus genome are capable of forming a stable (G = -18 kcal/mole) hairpin structure. Understanding the organization and gene expression of the X region may be crucial in expanding our knowledge on the biology of HBV. PMID- 2227262 TI - Hepadnavirus enhancer and its binding proteins. AB - In the hepadnavirus enhancer region, a 33 bp DNA sequence is strongly conserved among mammalian hepadnavirus genomes. To elucidate the role of the sequence, we tested enhancer activities and capability to form DNA-protein complex of several synthetic DNAs. Not only two tandem copies of a 46 bp DNA covering the sequence but also two tandem copies of a 23 bp in the sequence exhibit enhancer activity. Also the activity was augmented by treatment of a tumor promoter, TPA. DNA binding proteins complexes with the 23 bp DNA were augmented in extracts of HepG2 or HeLa cells stimulated with TPA. These results imply that the conserved sequence of hepadnavirus enhancer is a TPA-inducible enhancer which is transactivated by ubiquitous DNA-binding proteins. We presented results showing that DNA-protein complexes with a 23 bp DNA are similar to but distinct from those with a TPA-responsive element DNA, the recognition site for c-jun/fos products. We also presented results suggesting that hepadnavirus X protein may not directly or indirectly affect DNA-protein complex formation with the conserved sequence in the hepadnavirus enhancer. PMID- 2227263 TI - Open reading frames on plus strand genome of duck hepatitis B virus. AB - Hepadnaviruses have open reading frames of surface, core, polymerase and X protein on the minus strand of the genome. We analyzed a plus strand of duck hepatitis B virus (DHBV) for the presence of open reading frame with a computer program. We found one frame on the area that is complement to 3' end of polymerase gene and 5' end of precore gene. That open reading frame is conserved in three strains of DHBV, and the predicted protein is about 80 amino acids. PMID- 2227264 TI - Experimental WHV infection of woodchucks: an animal model of hepadnavirus-induced liver cancer. AB - Woodchuck hepatitis virus (WHV), a member of the Hepadnaviridae, is closely related to HBV in its virus structure, genetic organization and mechanism of replication. Natural infection of woodchucks is associated with chronic liver disease and primary hepatocellular carcinoma (HCC). A concerted effort to develop the woodchuck as an experimental animal model of hepadnavirus-induced disease was initiated in 1980. The experimental studies have established the following: (1) Chronic WHV carriage as an outcome of infection is a function of age of exposure, virus dose and, possibly, virus strain. As in humans, animals infected as newborns develop chronic antigenemia at high rates compared to young adults. (2) WHV causes primary hepatocellular carcinoma (HCC) in woodchucks. Hundred percent of experimentally-induced chronic WHsAg carriers developed HCC within three years; no HCC has occurred in concurrent uninfected control animals born and held in the same laboratory environment. The predictable course of experimental WHV infection leading to liver disease in woodchucks makes this an ideal model in which to study the natural history of hepadnavirus and to develop effective prophylactic and therapeutic strategies. PMID- 2227265 TI - HBV production in transgenic mice. AB - We produced transgenic mice by microinjecting a partially duplicated copies of hepatitis B virus (HBV) gene into fertilized eggs of C57BL/6 mice. One mouse was a high producer of HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the serum. All offspring carrying HBV DNA were positive for both antigens in the serum. The HBV DNA was expressed in liver- and kidney-specific manner. The normal process of HBV replication, including the packaging of the pregenome 3.5-kb RNA into a nucleocapsid, the reverse-transcription of the complete minus strand DNA, and the release of Dane particles into the serum before the completion of synthesis of plus strand, occurred in the liver of these transgenic mice. These results suggest that the species specificity of HBV infection is not due to the inability to replicate in nonnatural host but to the lack of receptors or factors needed for virus adsorption and internalization. The founder mouse is now 19 months of age but shows no clinical or pathological change, suggesting that HBV itself is not cytopathic. PMID- 2227266 TI - Development of transgenic mice containing woodchuck hepatitis virus DNA. AB - We produced transgenic mice containing woodchuck hepatitis virus DNA with tandem repeat structure capable of producing virus and viral antigens. Poly(A)+ RNAs probably corresponding to pregenome and viral antigens were detected in their liver. These mice have now been healthy for one year. However, there is the possibility of inducing immunologically mediated hepatitis. We anticipate these transgenic mice may present a useful model system for studying the significance of chronic hepatitis in hepatocellular carcinoma development. PMID- 2227267 TI - Hepatitis B virus DNA detection and comparison with hepatitis B surface antigen. AB - Hepatitis B surface antigen (HBsAg) has been used for the detection of hepatitis B virus (HBV). Recently, HBV detection using the polymerase chain reaction (PCR) has been shown to be a direct measure of complete virions and to be potentially a very sensitive method. Therefore, we attempted to analyze the relationship between HBsAg detection and HBV DNA assay by PCR. We tested HBV DNA by a modification of the PCR technique in serial sera from five chimpanzees experimentally infected with HBV and 29 human sera. Our new method of PCR analysis is as sensitive as former methods but is more simple and rapid than existing procedures. In chimpanzee studies, HBV DNA was detected 2-3 weeks before the appearance of HBsAg, and continued to be detectable 2 weeks after the production of antibody to HBsAg. Also, 3 of 11 chronic hepatitis B patients who lost HBsAg were positive for HBV DNA in serum, while all of patients who recovered from acute viral infection were negative for HBV DNA in serum. These results indicate that HBV DNA detection by PCR analysis is the most sensitive method currently available to detect the presence of complete virions in serum. PMID- 2227268 TI - Complementation analysis of mutants defective in different steps of HBV reverse transcription. AB - The HBV P gene encodes a multifunctional polyprotein which contains the major enzymatic activities required for hepadnaviral reverse transcription (protein primer, DNA polymerase, and RNase H). Mutant HBV genomes unable to synthesize fully functional P gene products were analysed for their potential to be rescued by a second mutant HBV genome that either contained a wild type P gene (intergenic complementation) or a mutation in a functionally different P gene domain (intragenic complementation). This analysis was carried out by cotransfecting two mutants at a time into HepG2 cells and assaying for the production of core particles containing DNA polymerase activity. The results obtained demonstrate the existence of intergenic, but not of intragenic complementation. This indicates that the primary P gene product is not processed before core assembly, and furthermore that there is a rather free mixing of all HBV gene products in the HBV infected cell which can lead to the efficient propagation of defective viral genomes. PMID- 2227269 TI - Hepatitis A, B, C, D and E viruses: structure of their genomes and general properties. AB - Hepatitis A virus is an enteric picornavirus. Its genome is a single stranded RNA molecule of positive-strand polarity of 7478 bases. This sequence codes for a polyprotein which is processed to give rise to viral proteins VP-1, VP-2, VP-3 and others. Hepatitis B virus, a major worldwide infectious and cancer promoting agent contains a DNA genome of 3226 base pairs that replicates by a reverse transcriptase via an RNA intermediate. Extensive sequencing and expression experiments have revealed four major genes named surface, core, polymerase and X which are coded in more than one reading frame. Furthermore, within a frame, proteins are expressed from multiple initiation codons resulting in several related products. The viral genome of hepatitis C virus (nonA-nonB), an elusive major infectious agent, has recently been cloned. This genome is a single positive-stranded RNA of at least 10,000 bases which codes for several antigens, some of them associated specifically with nonA-nonB hepatitis infections. The hepatitis D (delta) viral agent, an infectious agent requiring a hepadnarious for propagation, contains a covalently closed circular single-stranded RNA genome of 1167 nucleotides. This genome encodes the protein p24 and p27 that bind specifically to antisera from patients with chronic hepatitis D infections. PMID- 2227270 TI - Presentation of the Julius Friedenwald Medal to Rudi Schmid, M.D., Ph.D. PMID- 2227271 TI - Natural history of congestive gastropathy in cirrhosis. The Liver Study Group of V. Cervello Hospital. AB - In a prospective study of the natural history of congestive gastropathy, 212 consecutive cirrhotic patients (75 treated with sclerotherapy) were included. Mean follow-up was 46 months. Mild gastropathy (mosaiclike pattern) was found in 110 patients and severe gastropathy (granular mucosa with cherry spots) was found in 20. Prevalence of Helicobacter pylori, formerly Campylobacter pylori, was 50% in patients without, 43% in those with mild, and 28% in those with severe gastropathy. Congestive gastropathy was significantly more frequent in patients treated with sclerotherapy (83% vs. 50%, P less than 10(-5)). Sixty-month actuarial proportions of patients free of anemia (in the absence of hematemesis or melena), were 17% with severe, 62% with mild, and 93% without gastropathy (P less than 10(-8]. Corresponding figures for overt bleeding were 25%, 73%, and 87% (P less than 10(-7], whereas those for survival were 46%, 72%, and 85% (P = 0.0005), respectively. A multivariate regression analysis supported the following conclusions: (a) sclerotherapy and the presence of large esophageal varices significantly increase the risk of congestive gastropathy, which (b) is a significant risk indicator of both chronic and overt bleeding but does not independently affect survival. PMID- 2227272 TI - Multiple hormone elevations in Zollinger-Ellison syndrome. Prospective study of clinical significance and of the development of a second symptomatic pancreatic endocrine tumor syndrome. AB - In the present study of 45 patients with Zollinger-Ellison syndrome, the frequency and clinical importance of the release of multiple gastrointestinal peptides were assessed prospectively. During an initial evaluation, extent of gastrinoma, clinical symptoms, disease duration, and presence or absence of multiple endocrine neoplasia, type I (MEN-I) were assessed. All patients had determinations of fasting plasma gastrin, human pancreatic polypeptide, motilin, neurotensin, and somatostatin; 35 had determinations of insulin and gastrin releasing peptide and 21 had determinations of glucagon. A plasma elevation of additional peptides besides gastrin was detected in 62%, with 44% having one, 18% having two, and 0% having three additional peptides elevated. Motilin was elevated in 29%, human pancreatic polypeptide in 27%, neurotensin in 20%, and gastrin-releasing peptide in 10%, whereas insulin, glucagon, and somatostatin were not elevated in any patient. The presence or absence of elevation of any peptide did not differ in patients with or without MEN-I, with gastrinoma size, with the presence or absence of metastatic disease, or with various clinical symptoms. Patients were assessed yearly for clinical evidence of a secondary symptomatic pancreatic endocrine tumor syndrome with a median follow-up of 146 and 84 months from onset or diagnosis, respectively. Only one patient (2% of patients) developed a second syndrome (rate, 2 patients per 100 patients observed for 10 years). These results demonstrate that the plasma elevation of multiple gastrointestinal peptides is common in patients with Zollinger-Ellison syndrome; however, the rate of developing a second symptomatic pancreatic endocrine tumor syndrome is much lower than generally believed. Furthermore, no evidence is found to support the conclusions that the detection of the plasma elevation of these peptides is clinically important in assessing MEN-I status, disease extent, or presence of metastatic disease or that elevated levels of motilin, neurotensin, gastrin-releasing peptide, or human pancreatic peptide are associated with any distinct clinical symptoms. Therefore, we recommend that plasma concentrations of these additional gastrointestinal peptides should not be assessed routinely but rather only if new symptoms develop. PMID- 2227273 TI - Human pepsinogen A isozymogen patterns in serum and gastric mucosa. AB - The pepsinogen A isozymogen pattern in gastric mucosa is genetically determined and can be visualized in nondenaturating polyacrylamide gel electrophoresis of supernatants of sonified gastric mucosal biopsies by demonstrating proteolytic activity after converting pepsinogen into pepsin by acid. Pepsinogen isozymogens are present in very low concentrations in the blood but can now be demonstrated in serum by a newly developed immunoblotting procedure. This study investigated whether the serum pepsinogen A isozymogen pattern adequately reflects the pepsinogen A phenotype. Serum and gastric mucosal pepsinogen A isozymogen patterns were compared in 72 subjects from the routine endoscopy program. A close correlation was found between the relative intensities of the pepsinogen A isozymogens in the serum and the gastric mucosal patterns. Increasing the pepsinogen A release into the circulation by oral omeprazole did not affect the pepsinogen A patterns in the blood. It is concluded that the serum pepsinogen A pattern reflects the pepsinogen A phenotype in humans. In addition, no preferential release of a pepsinogen A isozymogen into the circulation was observed. Thus, immunoblotting of serum provides a new and reliable tool to study pepsinogen genetics in humans. Because a relationship was previously shown between specific pepsinogen A phenotypes and gastric malignancies in humans, serum pepsinogen A patterns may provide a tool to detect subjects who are at risk of gastric cancers. PMID- 2227274 TI - Effect of truncal vagotomy on parietal cell mass and antral gastrin cell mass in dogs. AB - Vagotomy is known to reduce acid secretion and to increase serum gastrin concentrations. However, there is minimal information on the effect of vagotomy on parietal cell mass or gastrin cell mass. Basal and maximal acid secretions and fasting serum gastrin concentrations were measured in 22 gastric fistula dogs with pyloromyotomy before and up to 56 days following complete bilateral truncal vagotomy (n = 11) or sham vagotomy (n = 11). Dogs underwent total gastrectomy on postoperative days 9 (n = 5 per group) or day 56 (n = 6 per group). Parietal cells were stained with Luxol fast blue and parietal cell mass determined with computer-assisted histomorphometry. Parietal cell mass averaged 10.68 +/- 0.90 billion in control dogs and correlated significantly with maximal acid output (r = 0.76; P less than 0.01). Vagotomy reduced maximal acid output by 40%-50% (P less than 0.001) but had no significant effect on parietal cell mass (8.99 +/- 1.00 billion). Vagotomy increased serum gastrin concentrations significantly, but antral gastrin cell mass in vagotomized dogs (5.66 +/- 1.00 million) was not significantly different than that in control dogs (4.74 +/- 0.50 million). Thus, vagotomy did not lead to parietal cell hypoplasia or gastrin cell hyperplasia despite profound alterations in parietal cell and gastrin cell function. PMID- 2227275 TI - 24-hour intragastric acidity and plasma gastrin after omeprazole treatment and after proximal gastric vagotomy in duodenal ulcer patients. AB - The relationship between suppressed gastric acidity and the increase in plasma gastrin levels after pharmacological and surgical treatment of peptic ulcer disease were compared in this study. Eight patients with chronic duodenal ulcer and referred for proximal gastric vagotomy were studied. 24-hour intragastric acidity and plasma gastrin levels were investigated in the same patients on three consecutive occasions: preentry without any treatment; after 4 weeks of administration of 20 mg of omeprazole daily, and 4-6 months after proximal gastric vagotomy. Intragastric acidity was slightly more reduced by omeprazole (94%) than after proximal gastric vagotomy (78%), with no difference found during the day or night with either. Plasma gastrin levels increased slightly more after proximal gastric vagotomy [284% (median, 2120 pmol.h/L; range, 733-2831 pmol.h/L)] than after omeprazole administration [186% (median, 1586 pmol.h/L; range, 495-2573 pmol.h/L)]. There is strong evidence that the increased plasma gastrin concentration following omeprazole treatment is caused by the reduced intragastric acidity. The slight increase in plasma gastrin concentration following proximal gastric vagotomy despite a lesser reduction in intragastric acidity may be the result of additional effects on gastrin release by the vagotomy. Both treatments resulted in a modest increase in plasma levels of gastrin that were far below the gastrin levels observed in achlorhydric patients, e.g., patients with pernicious anemia. PMID- 2227276 TI - Role of epidermal growth factor, prostaglandin, and sulfhydryls in stress-induced gastric lesions. AB - Epidermal growth factor promotes the growth of and protects gastric mucosa against various ulcerogens, including stress, but little is known about its role in the pathogenesis of stress ulcerations. In this study, Wistar rats with intact and resected salivary glands were exposed to water-immersion and restraint stress. During 2-14 hours of water-immersion restraint stress, the formation of gastric ulcerations increased progressively and the duration of stress was accompanied by a decrease in DNA synthesis in the gastric mucosa. Following sialoadenectomy, a significant increase in the number of stress ulcerations and further reduction in DNA synthesis were observed. Exogenous epidermal growth factor and dimethyl prostaglandin E2 significantly reduced the ulcerations in the stressed rats with intact salivary glands, but this reduction was significantly less pronounced after sialoadenectomy. Water-immersion restraint stress also resulted in about 50% reduction in mucosal prostaglandin E2 generation, and the pretreatment with indomethacin, which suppressed prostaglandin E2 by about 90%, almost doubled the number of stress ulcerations and abolished the gastro protective effect of exogenous epidermal growth factor (but not dimethyl prostaglandin E2) against the stress lesions. An inhibition of ornithine decarboxylase activity by difluoromethyl ornithine also augmented stress-induced ulcerogenesis and abolished the protective action of epidermal growth factor while the administration of spermine almost completely prevented stress ulcerations in rats both without and with pretreatment with difluoromethylornithine. Water-immersion restraint stress also significantly reduced mucosal content of glutathione. Cysteamine increased tissue glutathione and reduced stress ulcerations but N-ethylmaleimide, an sulfhydryl blocker, decreased mucosal content of glutathione without affecting the stress ulcerations. This study indicates that the stress ulcers are accompanied by the reduction in mucosal synthesis of DNA, prostaglandin, and glutathione and that the presence of salivary glands attenuates the stress ulcerogenesis probably by releasing epidermal growth factor which acts, in part, by enhancing ornithine decarboxylase activity, mucosal growth, and prostaglandin and glutathione formation. PMID- 2227277 TI - Comparison of salsalate and aspirin on mucosal injury and gastroduodenal mucosal prostaglandins. AB - The effects of a 7.5-day course of orally administered salsalate (3.0 g/day), aspirin (3.9 g/day), or placebo on gastroduodenal mucosal injury, mucosal prostaglandin content, and plasma prostaglandin concentrations in healthy, asymptomatic human volunteers were examined. Mean serum salicylate concentrations after these doses of salsalate and aspirin were nearly identical (approximately 15 mg/dL). When the gastroduodenal mucosa was assessed endoscopically 1 hour after the final dose of medication, there was minimal mucosal injury in placebo treated or salsalate-treated subjects and considerable injury in the stomach and duodenum of aspirin-treated subjects (P less than 0.001, aspirin vs. salsalate or placebo). In both the stomach and duodenum, aspirin lowered mucosal prostaglandin F2a and E2 content by greater than 90% (P less than 0.001), whereas salsalate produced no significant change. Aspirin also lowered plasma prostaglandin F2a concentrations by 58% +/- 6%, whereas salsalate lowered them by only 11% +/- 9% (P less than 0.001). Thus, the nonacetylated salicylate, salsalate, produced much less gastroduodenal mucosal damage than aspirin at equivalent serum salicylate concentrations, possibly because salsalate did not inhibit mucosal prostaglandin synthesis. PMID- 2227278 TI - Detection of duodenal gastrinomas by operative endoscopic transillumination. A prospective study. AB - The ability of operative endoscopic transillumination of the bowel wall to detect duodenal gastrinoma was evaluated prospectively in 26 patients with the Zollinger Ellison syndrome. The results were assessed by exploratory laparotomy and compared with the results of other localization techniques. Twelve duodenal gastrinomas were resected from 10 patients. Operative endoscopic transillumination detected 10 of the 12 gastrinomas, a sensitivity of 83%, which was significantly greater (P less than 0.05) than that for either preoperative imaging (25%) or intraoperative ultrasonography and palpation (42%). The sensitivity of operative endoscopic transillumination was a result of the ability to detect focal areas that did not transilluminate on the serosal side of the duodenum, and not the mucosal appearances seen through the endoscope, which were not helpful. Operative endoscopic transillumination detected gastrinomas less than 1 cm in diameter throughout the duodenum. Of the patients in this study, 39% had duodenal gastrinomas, a greater frequency than previously reported. These results indicate that operative endoscopic transillumination is the most sensitive technique yet described for detecting duodenal gastrinomas and should be performed routinely in all patients with the Zollinger-Ellison syndrome who undergo exploratory laparotomy for cure. PMID- 2227279 TI - Acute and chronic stress in duodenal ulcer disease. AB - Acute and chronic life event stressors were objectively assessed in a sample of duodenal ulcer patients and community controls. Stress was assessed on two dimensions, "personal threat" and "goal frustration." Chronic stressors (those of 6 months' duration or more) involving high goal frustration were significantly and independently associated with the onset and relapse of duodenal ulcers, as were acute events of high immediate but transient personal threat. PMID- 2227280 TI - Choledochoduodenal flow: effect of the sphincter of Oddi in opossums and cats. AB - The aim of this study was to test in vivo (a) whether the sphincter of Oddi acts as a resistor or also as a pump, (b) the effect of an IV infusion of cholecystokinin (CCK) on choledochoduodenal flow, and (c) the ability of the choledochoduodenal junction to prevent duodenobiliary reflux in two animal species, opossums (n = 11) and cats (n = 8). Opossums were implanted with bipolar electrodes on the sphincter of Oddi and the adjacent duodenum. Cats were not. Experiments were performed in vivo using a propulsion evaluation system to test whether the Sphincter of Oddi was able to pump fluid from the bile duct to the duodenum against pressure gradients. In 5 opossums and 4 cats, choledochoduodenal flow was evaluated during the IV infusion of CCK (20 ng.kg-1.min-1). The opossum sphincter of Oddi moved fluid against duodenal pressure gradients of 6-45 cm H2O. The spike-burst frequency (6.4 +/- 1.7 min-1) was maximal at peak bile duct pressures and decreased as bile duct pressure decreased (4.9 +/- 1.6 min-1; P less than 0.001). Pressure pulses in the bile duct were observed at a frequency that correlated with sphincter of Oddi spike-burst frequency (r = 0.84; P less than 0.001). In cats, choledochoduodenal flow occurred only along a hydrostatic gradient; the sphincter of Oddi never acted as a pump but only as a resistor. Infusion of CCk significantly increased the frequency of sphincter of Oddi contractions in opossums, but the transfer of fluid from bile duct to duodenum was significantly reduced. In cats, the rate of fluid flow from the bile duct to the duodenum during CCK infusion did not differ from control values. Reflux of duodenal fluid into the biliary tree was never observed, even at duodenal pressures as high as 100 cm H2O. In conclusion, in vivo, the sphincter of Oddi is able to pump fluid from the bile duct to the duodenum against a pressure gradient in opossums, but, in cats, choledochoduodenal flow requires a bilioduodenal pressure gradient. The increase in sphincter of Oddi contraction frequency induced by CCK in opossums resulted in a decrease in active transsphincteric flow. Duodenobiliary reflux could not be elicited in opossums and cats under the conditions of these experiments. PMID- 2227281 TI - Amines protect in vitro the celiac small intestine from the damaging activity of gliadin peptides. AB - Proteins and peptides responsible for the celiac small intestinal lesion inhibit both the enterocyte recovery of in vitro cultured flat celiac mucosa and the in vitro development of fetal rat intestine. They also agglutinate K 562 (S) cells. Using these three in vitro systems (cultured human celiac and rat fetal intestine and cell agglutination), it is shown that several small-molecular-weight amines, mostly the polyamines spermidine and spermine, prevent and reverse K 562 (S) cell agglutination induced by gliadin peptides, whereas they do not prevent cell agglutination induced by concanavalin A and wheat germ agglutinin. Some of these amines also protected in vitro developing fetal rat intestine and flat celiac mucosa from the damaging effect of gliadin peptides. This protective effect may be related to the trophic activity exerted by amines on the intestine and/or the effect of amines on the functions of intestinal brush border or intracellular membranes involved in the intestinal handling of gliadins. PMID- 2227282 TI - Role of visceral afferent mechanisms in functional bowel disorders. AB - This report analyzes the clinical and physiological evidence supporting a role for altered visceral afferent mechanisms in the pathogenesis of two functional bowel syndromes: noncardiac chest pain and the irritable bowel syndrome. Considerable recent evidence indicates that increased contractility is present only in a minority of patients and that hypercontractile episodes are not temporally related to abdominal pain. In contrast, altered sensation and motor reflexes in response to physiological stimuli, such as mechanical distention or acid, is common when appropriately investigated. The vagal and spinal afferent innervation mediates visceral sensation and is involved in multiple reflex loops regulating gastrointestinal effector function, such as motility and secretion. Sensory input can be modulated peripherally at the afferent nerve terminal, at the level of prevertebral ganglia, the spinal cord, and the brainstem. An up regulation of afferent mechanisms would result both in altered conscious perception of physiological stimuli and in altered motor reflexes. Current evidence is consistent with an alteration in the peripheral functioning of visceral afferents and/or in the central processing of afferent information in the etiology of altered somatovisceral sensation and motor function observed in patients with functional bowel disease. PMID- 2227284 TI - Intravenous but not intracolonic epidermal growth factor maintains colonocyte proliferation in defunctioned rat colorectum. AB - The role of epidermal growth factor in the proliferation of normal and premalignant colonocytes in vivo is not fully understood. In particular, the relative importance of its possible systemic and intraluminal routes of action has not been fully clarified. Rats with surgically defunctioned distal colorectums were used, and mini osmotic pumps were implanted to study the effects of intraluminal and IV administration of epidermal growth factor on colonocyte proliferation. Within 2 weeks of bypass, colonocyte proliferation in defunctioned colorectum has decreased to about one third the rate in normal colorectum or in colorectum proximal to the defunctioning colostomy. Intraluminal epidermal growth factor, infused from the time of operation did not reverse this hypoplasia, whereas IV epidermal growth factor maintained colonocyte proliferation at approximately the normal rate in bypassed colorectum. This model is suitable for testing other putative colonic mitogens for possible intraluminal and systemic effects. PMID- 2227283 TI - Excremental studies in human neonates. Identification of zinc coproporphyrin as a marker for meconium. AB - Zinc coproporphyrin, isomers I and III (I:III ratio, approximately 8:1), was identified in human meconium using high-performance liquid chromatography, ultraviolet-visible absorbance spectroscopy, and emission fluorescence spectroscopy. The high levels of zinc coproporphyrin in the first stools of life decrease steadily as meconium is evacuated and reach a plateau at comparatively negligible levels after complete evacuation of meconium. Zinc coproporphyrin can be used as a marker for human meconium. PMID- 2227285 TI - Glucose disposal, beta-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment. AB - Factors controlling glucose metabolism after IV load were studied in nine patients with compensated cirrhosis and in six age-matched controls. The time courses of glucose, insulin, and C peptide were analyzed by means of the minimal model technique. In cirrhosis, insulin sensitivity was reduced by approximately 70% and glucose-dependent glucose uptake (glucose effectiveness) by 45%. Decreased glucose effectiveness explained 65% of the variance of glucose disappearance and correlated with the ratio of urinary creatinine to height, an independent measure of muscle mass (r = 0.839). beta-cell responsiveness to glucose, measured on C-peptide kinetics, was variable and increased on average by 170% and 107% (first-phase and second-phase, respectively). The total amount of insulin secreted by beta-cells in the course of the study was nearly doubled, whereas the basal insulin secretion rate was in the normal range. The time courses of hepatic extraction of insulin did not differ between groups, and basal extraction was on average 58% in controls and 56% in patients with cirrhosis. It was reduced to 30% in a single patient who had severe hepatocellular failure and large spontaneous portosystemic shunting. We conclude that the alterations in glucose metabolism of cirrhosis include a decreased insulin sensitivity, a reduced glucose effectiveness, and an increased pancreatic responsiveness to glucose, leading to hyperinsulinemia. The hepatic extraction of insulin is reduced only in the very advanced stages of the disease, possibly because of a large reserve capacity of the hepatic parenchyma. PMID- 2227286 TI - Host response to mycobacterial infection in the alcoholic rat. AB - Animals, chronically treated with alcohol, were inoculated with mycobacteria (bacillus Calmette-Guerin, 10.2 x 10(6) organisms) into the spleen to produce a granulomatous hepatitis. Before infection, chronic alcohol ingestion was associated with a depressed skin test response to phytohemagglutinin, 71.7% of baseline (P = 0.009). Mycobacterial (bacillus Calmette-Guerin) infection stimulated phytohemagglutinin skin test response to 417% of baseline in controls and 299% in alcoholics (P less than 0.001). The hepatic granuloma response was altered with smaller but more numerous granulomas (mean +/- SEM, 81.2 +/- 1.5 microns2 of area with a frequency of 1.8 granulomas per field in alcoholics vs. 129.8 +/- 5.71 microns2 and 1.2 granulomas per field in controls; P less than 0.001). These changes were associated with a 10-fold increase in colony-forming units per gram of liver (54.5 +/- 18.2 in alcoholics vs. 5.6 +/- 1.83 in controls; P = 0.0006). This model offers precise parameters for host response to infection and indicates that alcohol significantly impairs the clearing capacity for mycobacteria from the liver. PMID- 2227287 TI - Hepatitis B virus DNA in liver and peripheral blood mononuclear cells during reduction in virus replication. AB - Changes in hepatitis B virus DNA in blood cells and liver were studied in 34 patients (12 controls, 22 under therapy). There were no basal differences in the presence of the viral genome in blood cells between treated and control patients. A significant decrease in the percentage of patients with viral genome in blood cells was observed in patients who lost this marker in serum. Replicative intermediates of the viral genome were observed in the basal liver samples from all patients. In patients who lost the viral DNA in serum, hepatitis B virus genome became undetectable in the second liver sample in all but two patients who had viral sequences integrated in the host genome. Replicative intermediates were found in all patients with serum viral DNA. The results of this study suggest that there may be a relation between the disappearance of hepatitis B virus DNA in liver and blood cells. PMID- 2227288 TI - Effect of loxiglumide, a cholecystokinin antagonist, on pancreatic polypeptide release in humans. AB - The purpose of this study was to determine the role of cholecystokinin in the regulation of postprandial pancreatic polypeptide secretion in humans. The pancreatic polypeptide responses to modified sham feeding and gastric instillation of a test meal were first compared with the response to oral ingestion of the same meal. The experiments were repeated under cholinergic (atropine) and cholecystokinin (loxiglumide) blockade. Atropine completely abolished the pancreatic polypeptide response to sham feeding and caused significant reductions after gastric and oral food intake. Loxiglumide, on the other hand, significantly reduced pancreatic polypeptide release to oral food (51% inhibition) without affecting the response to sham feeding. In separate experiments using a duodenal perfusion system, the effects of atropine and loxiglumide on intestinal phase-stimulated pancreatic polypeptide release were examined, and both cholinergic and cholecystokinin blockade induced complete suppression. It was concluded (a) that cholecystokinin is involved in postprandial pancreatic polypeptide response, especially during the intestinal phase stimulation, and (b) that the cholinergic system is crucial and superimposed on cholecystokinin in stimulating pancreatic polypeptide release. PMID- 2227289 TI - Are diets associated with different rates of human interdigestive and postprandial pancreatic enzyme secretion? AB - To determine if diets are associated with different rates of interdigestive and postprandial enzyme secretion and how quickly enzyme secretion is modulated by nutrients, 27 healthy humans were randomly selected to follow one of five diets. The calorie proportions of carbohydrate, fat, and protein in each diet was assigned by a mixture design. After the subjects followed a diet for 2 weeks, they were intubated with an oroduodenal tube, and enzyme outputs were measured during the interdigestive period and after eating a meal identical to meals eaten during the previous 2 weeks. For the next 24 hours subjects either followed the same diet or a diet that contained the same amount of fat, but the percent of carbohydrate and protein was changed by 30%. Then interdigestive and postprandial pancreatic enzyme outputs were remeasured. After 2 weeks, diets containing the most carbohydrate (50%-80%) were associated with the lowest interdigestive and postprandial amylase and lipase (P less than 0.05) and trypsin outputs (P less than or equal to 0.05). In contrast, diets containing the most fat (40%) were associated with the highest interdigestive and postprandial outputs of amylase (P less than 0.05) and trypsin (P less than 0.05). Maintaining or altering diets for 24 hours did not change interdigestive pancreatic enzyme outputs, but postprandial amylase output was significantly increased (P less than 0.05) by increasing protein and decreasing carbohydrate content of the diets by 30% for 24 hours. We conclude that diets containing a high proportion of calories as carbohydrate for 2 weeks are associated with lower interdigestive and postprandial pancreatic secretion than diets that have a high fat content. In response to diets, changes in postprandial pancreatic enzyme secretion occur within 24 hours whereas changes in interdigestive secretion (no nutrients in the lumen) occur after 24 hours. PMID- 2227290 TI - Pathogenesis of ceftriaxone-associated biliary sludge. In vitro studies of calcium-ceftriaxone binding and solubility. AB - Ceftriaxone, a semisynthetic third-generation cephalosporin, has recently been associated with biliary sludge formation. Analysis of the biliary concretions induced by this agent shows a calcium salt of ceftriaxone. The present in vitro studies were undertaken to provide insight into the pathogenesis of ceftriaxone associated biliary sludge formation by evaluating possible interactions that may exist between calcium, bile salts, and ceftriaxone. Ceftriaxone possessed high calcium-binding affinity. The formation constant for the calcium ceftriaxone salt at 37 degrees C was about 157.3 L/mol; stoichiometry of the salt was 1:1, i.e., calcium ceftriaxone. The calcium-binding property of ceftriaxone was observed to be additive to that of taurocholate in mixed taurocholate-ceftriaxone solutions. Although the solubility product constant for calcium ceftriaxone was only 1.62 x 10(-6) mol/L2, marked metastability was observed; neither visible nor microscopic precipitates developed until the [Ca2+] x [ceftriaxone] ion product exceeded the solubility product constant by a factor of 10.4. Metastability of the calcium ceftriaxone salt was also observed in human gallbladder bile in vitro. Estimates of human biliary calcium ceftriaxone solubility in vivo were than calculated from previously-reported values for biliary [Ca2+], [ceftriaxone], and from the solubility product constant as defined in this study. Calculated saturation indices for calcium-ceftriaxone in human bile generally increased (corresponding to a decrease in solubility) with increasing ceftriaxone dose. At doses less than or equal to 1 g, saturation index was well within the metastable range of this calcium-salt. However, at doses greater than or equal to 2 g, the saturation index surpassed the metastable limit. Under these conditions, precipitation of ceftriaxone could occur. It was concluded that the development of ceftriaxone induced biliary sludge is a solubility problem that occurs in patients receiving high-dose treatment (greater than or equal to 2 g). This study proposes that the risk of developing ceftriaxone-associated biliary "pseudolithiasis" increases with increasing ceftriaxone dose and in patients with impaired gallbladder emptying. PMID- 2227291 TI - Gallbladder motility in cholesterol gallstone disease. Effect of ursodeoxycholic acid administration and gallstone dissolution. AB - Gallbladder motility was evaluated by ultrasonography in 75 cholesterol gallstone patients and in 77 matched control subjects. All 75 gallstone patients were candidates for oral bile acid therapy (radiolucent gallstones, less than 2 cm in diameter, in well-opacified gallbladder), and 38 of them were also studied during ursodeoxycholic acid administration. An additional 20 gallstone patients were studied 1 year after confirmed gallstone dissolution with oral bile acids. Gallstone patients showed significantly greater fasting and residual volumes, a decreased percent of gallbladder emptying, but a similar absolute emptying and emptying rate compared with the control subjects. Greater fasting volumes and reduced percents of gallbladder emptying were also found in gallstone-free patients who achieved complete dissolution with oral bile acids. After ursodeoxycholic acid administration, fasting gallbladder volumes were greater, and percents of gallbladder emptying were further decreased than in untreated gallstone patients. In conclusion, greater fasting volumes, and not reduced gallbladder contractility, account for the defective gallbladder function in radiolucent (cholesterol-rich) gallstone patients. This condition is likely to precede, and possibly to promote, gallstone formation because it persists after gallstone dissolution. Ursodeoxycholic acid administration worsens the defect observed in gallstone patients. This finding also suggests, although indirectly, that the expected normalization of cholesterol saturation during oral bile acid administration is not paralleled by an improvement in gallbladder function. PMID- 2227293 TI - Long-term outcome after surgery for biliary atresia. Study of 40 patients surviving for more than 10 years. AB - To define long-term prognosis of children who underwent surgery for biliary atresia, a retrospective study was undertaken in 122 children who underwent one of the Kasai procedures between 1968 and 1977. Forty of the 122 children (32.7%) were alive after 10 years. Firm hepatomegaly was present in 31 and splenomegaly in 29 children. Serum bilirubin or all liver function tests were normal in 21 and 11 children, respectively; survival rate decreased with the age at operation, but no significant difference was observed in the rate of children surviving with normal serum bilirubin whether they underwent surgery before age 2 months or between 2 and 3 months. Twenty-four had esophageal varices and 15 experienced gastrointestinal bleeding. Normal liver-function tests and absence of portal hypertension were observed in 11 of 122 children. These results indicate that Kasai's procedures were helpful in a significant proportion of children with biliary atresia who underwent surgery during this period. However, 80% of children who initially underwent surgery with Kasai's procedures should eventually undergo liver transplantation. PMID- 2227292 TI - Primary biliary cirrhosis. Quantitation of autoantibodies to purified mitochondrial enzymes and correlation with disease progression. AB - Primary biliary cirrhosis is characterized by the presence of antimitochondrial antibodies. Recently, six of the autoantigens have been identified as components of the 2-oxo acid dehydrogenase multienzyme complexes located within mammalian mitochondria. Immunoblotting studies have shown that two of these components, namely E2 and protein X of pyruvate dehydrogenase complex, are the major antigenic polypeptides recognized by autoantibodies. This study shows the development of an enzyme-linked immunosorbent assay to detect and quantitate antibodies to these two purified antigens. Coded serum samples from 166 patients with primary biliary cirrhosis, 140 patients with other liver and/or autoimmune disease, and 52 normal women were analyzed for reactivity using this immunoassay. These results indicate that this rapid, simple method has a 93% sensitivity and 96% specificity in the diagnosis of primary biliary cirrhosis. The titer of immunoglobulin G autoantibodies correlated not only with antimitochondrial antibody titer measured by indirect immunofluorescence (P less than 0.0001) but also with histological stage of disease (P less than 0.04) and prognostic biochemical variables such as higher serum bilirubin and lower serum albumin levels (P = 0.038 and 0.028, respectively). There was no significant correlation between titer of autoantibodies and serum globulin or immunoglobulin G levels, indicating that the positive correlation with disease progression was not secondary to hypergammaglobulinemia. PMID- 2227294 TI - Phospholipase C and diacylglycerol lipase in human gallbladder and hepatic bile. AB - A phospholipase C in bile, free of bacterial infection, has recently been identified from cholesterol gallstone patients. Because of the importance of phosphatidylcholine in solubilizing cholesterol in bile, this study further investigates the metabolism of phosphatidylcholine in delipidated gallbladder and common bile duct biles. Phospholipase C activity, as measured by the release of phosphoryl[3H]choline from the substrate 1,2-dipalmitoyl-sn-glycero-3-phospho [N methyl-3H]choline, was identified in both hepatic and gallbladder biles. Similar levels of activity (nmol.h-1.mg-1 of delipidated protein) were found in common bile duct (11.25 +/- 14.23) and gallbladder bile (19.07 +/- 22.24), although per milliliter of bile, the mean gallbaldder levels were 6.4 times greater than those found in common duct bile. With the tow substrates, 1-palmitoyl-2[9,10-3H] palmitoyl-sn-glycero-3-phosphocholine and 1,2(1-14C) dipalmitoyl-sn-glycero-3 phosphocholine, the majority of organically extracted label, after thin-layer chromatography, was recovered as radiolabeled diglyceride, confirming the presence of phospholipase C. Diglyceride levels were found to be closely correlated with [3H]choline (slope, 0.9820; r = 0.9844). In addition to diglyceride, both radiolabeled free fatty acid and monoglyceride were identified in common bile duct and gallbladder biles, although their levels were an order of magnitude less than measurable phospholipase C activity. To determine whether the free fatty acid release was due to either a diacylglycerol-lipase or a phospholipase A2, the effect of adding unlabeled diglyceride on free fatty acid formation from the substrate [14C]DPPC was examined. As the concentration of unlabeled diglyceride was increased, the amount of free fatty acid and monoglyceride released were both reduced in parallel. Direct measurement of diacylglycerol-lipase activity by incubating the diglyceride, sn 2[3H]dipalmitoyl, resulted in release of both products in a ratio similar to that found with sn-2[3H]DPPC. Finally, no radiolabeled lysolecithin was identified with [3H]choline-DPPC or [14C]DPPC as substrate indicating the free fatty acid was the product of a diacylglycerol-lipase rather than a phospholipase A2. Phospholipase C and diacyl-glycerol-lipase activities were significantly correlated (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2227295 TI - Microprocessor-assisted solvent-transfer system for gallstone dissolution. In vitro and in vivo validation. AB - To improve the efficacy, safety, and convenience of contact dissolution of gallbladder stones, a microprocessor-assisted solvent transfer system was developed. The system's two pumps simultaneously infuse and aspirate solvent into and from the gallbladder at a high flow rate through a multilumen catheter. The microprocessor controls the pumps using a closed feedback loop control algorithm to regulate intragallbladder pressure to prevent solvent escape into the duodenum. Turbulent solvent flow at the catheter end in the gallbladder is designed to induce rapid stone dissolution and to suspend insoluble residue, thus promoting its aspiration. The system's response and gallbladder emptying capacity was 160-fold faster than the natural gallbladder emptying rate. The rate at which gallstones were dissolved by methyl tert-butyl ether using the system was compared with that achieved with a syringe pump. For 6 of 11 pairs of stones that totally dissolved, the mean dissolution time with the system was 10 +/- 6 minutes compared with 112 +/- 81 minutes for the syringe pump. In the 5 of 11 stone pairs which dissolved incompletely, insoluble residue was completely eliminated by the system in 21 +/- 9 minutes but not by the syringe pump even at 360 minutes. When the system was used in gallstone patients, solvent recovery was 99% +/- 1%, and the concentration of a nonabsorbable marker did not change, confirming the lack of appreciable absorption of methyl tert-butyl ether. These studies suggest that the microprocessor-assisted solvent transfer system is a device capable of safe, complete, and fully automatic contact dissolution of cholesterol gallbladder stones using methyl tert-butyl ether or similar solvents. PMID- 2227296 TI - Adaptive hyperphagia in patients with postsurgical malabsorption. AB - The specific nutritional consequences of malabsorption after small-bowel surgery were studied in a consecutive series of 48 ambulatory patients who had had small bowel resection (n = 43) or bypass (n = 5) and in 10 patients who had an ileal pouch (n = 10). The patients received a 3-day standardized oral regimen providing daily 30 kcal/kg of ideal body weight (IBW). Throughout the study, 41 patients had malabsorption (fecal fat greater than 5%); 17 had fecal fat less than 5% and served as controls. The malabsorption patients absorbed 70% of protein and 71% of fat. Twenty-one were normonourished and 20 had features of mild energy malnutrition, vs. 15 and 2 controls, respectively. Compared with controls, malabsorption patients had decreased body weight and triceps skin-fold but no features of protein malnutrition. their mean daily food intake at home was significantly enhanced (39.6 +/- 13.1 kcal/IBW kg) vs. controls (28.8 +/- 5.8 kcal/IBW kg, P less than 0.001). In the malabsorption group, caloric intake was higher in the normonourished patients than in those with mild malnutrition. This study shows that a chronic malabsorption has limited nutritional consequences. The patients compensate for their absorptive handicap by increasing their oral intake. PMID- 2227297 TI - Esophageal obstruction after ingestion of a fiber-containing diet pill. AB - Foreign bodies of the esophagus in adults may be the result of a food bolus that becomes lodged proximal to a structural abnormality of the distal esophagus. A case of peptic stricture of the esophagus in a patient who presented with acute dysphagia after ingesting an over-the-counter diet pill composed of guar gum is discussed. It is recommended that anorectics composed of dietary fiber should not be used in patients with a history of esophageal stricture. PMID- 2227298 TI - Idiopathic biliary ductopenia in adults: a report of five cases. AB - The clinical and pathological findings of five adult cases of idiopathic nonsyndromatic paucity of interlobular bile ducts are reported. Patients were 18 32 years old at the onset of the disease; four presented with pruritus and/or jaundice and one with bleeding of the esophageal varices. Two patients were siblings. Serum alkaline phosphatase counts ranged from 1 to 16 times the upper normal value, and total bilirubin counts ranged from 0.6 to 8.8 mg/dL (10 to 150 mumol/L). Initial liver biopsy showed portal and periportal fibrosis with cholangiolar proliferation and reduction in the number of interlobular bile ducts. Antimitochondrial antibodies were absent, and bile ducts were normal after opacification. The patients were observed for 3-11 years. Repeated liver biopsies in the five patients showed progression of the lesions, with development of biliary type cirrhosis in four. Two of the four patients with cirrhosis died of hepatic failure 3 and 11 years after onset of the disease. In the two other cases, liver transplantation was performed successfully. These cases suggest that chronic cholestasis with marked ductopenia resembling the nonsyndromatic paucity described in infancy and childhood may reveal itself at an adult age. This disorder, possibly familial, may rapidly progress to severe and even fatal liver disease and could be a new indication for liver transplantation. PMID- 2227300 TI - Heterotopic liver transplantation for fulminant Wilson's disease. AB - Wilson's disease may present with severe acute hepatocellular failure. The only effective treatment for fulminant Wilson's disease is liver transplantation, which may lead to reversal of the underlying disease. Some patients with cirrhosis who are too ill to undergo orthotopic liver transplantation have been treated with heterotopic liver transplantation. However, use of heterotopic liver transplantation for fulminant hepatocellular failure has not been successful. This case study involves a patient in whom a heterotopic liver transplant was successfully used for treatment of Wilson's disease presenting with fulminant hepatocellular failure. PMID- 2227299 TI - Omeprazole in the management of intractable esophageal ulceration following injection sclerotherapy. AB - Transient esophageal ulceration is a common finding after sclerotherapy of varices. A small proportion of these ulcers become chronic and resistant to conventional therapy. Such chronic ulcers have been associated with pain, stricture formation, and recurrent hemorrhage. The use of omeprazole, a proton pump inhibitor, was examined in the current study in the treatment of 10 patients (6 women, 4 men; age range, 27-86 years) with cirrhosis (PBC, 4; sclerosing cholangitis, 2; chronic active liver disease, 2; alcohol, 1; and cryptogenic, 1) who developed an esophageal ulcer after a mean of 13 (range, 8-21) sessions of sclerotherapy. The ulcers had been present for 3-54 months despite prolonged treatment with high-dose H2-receptor antagonists and sucralfate. In each case one or more complications had occurred: severe pain in 3, stricture formation in 4, and recurrent hemorrhage in 7 cases. After an 8-week course of omeprazole, 40 mg daily, endoscopy confirmed complete healing of the ulceration in all 10 cases with symptom resolution. In 2 cases the ulcer recurred, with associated bleeding within 6 weeks of discontinuing the treatment in 1 patient. Both cases responded to repeat therapy. These results confirm the efficacy of omeprazole for postsclerotherapy ulceration and imply that acid-pepsin has a role in perpetuating such ulcers. PMID- 2227301 TI - Caseating hepatic granulomas in Hodgkin's lymphoma. AB - A 68-year-old man presented with recurrent Hodgkin's lymphoma after a 9-year disease-free interval induced by chemotherapy. In addition to histological evidence of recurrent Hodgkin's disease, the liver biopsy specimen showed extensive caseating granulomas. Cultures of bone marrow and liver tissue tested negative for Mycobacterium tuberculosis. No antituberculous treatment was administered, and the patient had an excellent clinical response to additional chemotherapy for lymphoma. Hodgkin's lymphoma should be added to the list of disease entities associated with caseating granulomas in the liver. PMID- 2227302 TI - An immunohistological study of the human enteric nervous system with microtubule associated proteins. AB - Immunohistochemical study of normal intestines from six infants and children with monoclonal antibodies against microtubule-associated proteins showed that microtubule-associated proteins 5 and tau were excellent markers of the enteric nervous system. Compared with neuron-specific enolase, microtubule-associated proteins 5 and tau had similar distribution but gave more cellular details showing a cytoskeleton of microtubules in neuroplasm. Unlike S100 protein, microtubule-associated proteins 5 and tau were neuron specific and were absent from glial cells. More enteric neurons contained microtubule-associated proteins 5 and tau than neurofilament proteins. Of the other microtubule-associated proteins, microtubule-associated protein 2 was present in only a few enteric neurons and microtubule-associated protein 1 was entirely absent. PMID- 2227303 TI - Esophageal tests for all seasons and all reasons but ... how do they help the patient??? PMID- 2227304 TI - What is functional disease and how do you measure it? PMID- 2227305 TI - Surveillance after colon cancer: is it worthwhile? PMID- 2227306 TI - Delayed measurement of bicarbonate secretion in vitro. PMID- 2227307 TI - Abnormal drug metabolism in chronic pancreatitis: treatment with antioxidants. PMID- 2227308 TI - The prevalence of hemorrhoids and chronic constipation. PMID- 2227309 TI - Eicosanoids in amebiasis. PMID- 2227310 TI - Reflux esophagitis in Zollinger-Ellison syndrome. PMID- 2227311 TI - Ulcer healing: does omeprazole efficacy depend on daytime or 24-hour acid inhibition? PMID- 2227312 TI - Colonic lipomas: outcome of endoscopic removal. AB - Colonic lipomas are benign adipose tumors which are usually submucosal. With the increase in the number of endoscopic procedures being performed, these tumors are often detected incidentally at colonoscopy. Although the risks of removing these tumors have been recognized, numerous reports have documented safe removal by snare electrocautery. We have reviewed the clinical outcome and the endoscopic and histopathologic features of seven lipomas that were endoscopically removed over a 5-year period. Four patients recovered uneventfully, while three patients (42.8%) developed colonic perforation after the polypectomy. In the latter group, the lipomas were significantly larger than they were in the patients who did not develop colonic perforation (1.9 +/- 0.4 and 4.2 +/- 0.7 cm, respectively; p = 0.048). Furthermore, the polypectomy specimens from those patients who developed perforation all contained significant muscularis propria. Lipomatous polyps that are identified at endoscopy to be greater than or equal to 2 cm in diameter and to have a limited pedicle are at the greatest risk for endoscopic perforation. PMID- 2227313 TI - A laser-induced scar at the cardia increases the yield pressure of the lower esophageal sphincter. AB - Low yield pressure of the lower esophageal sphincter is associated with esophageal reflux, and fundoplication must increase yield pressure if it is to prevent reflux. We attempted to increase yield pressure endoscopically in the dog by using the Nd:YAG laser to produce a fibrous scar at the cardia in the approximate line of the gastric sling fibers. Ten beagle dogs were studied. In a pilot study with two dogs, 15 watts for 4.2 sec were found to produce a scar deep into the muscle coat of the stomach. Three configurations of scar were used. One produced significant rises in yield pressure in all four of the dogs treated, the second produced a significant rise in one of the two dogs treated, and the third caused a significant drop in yield pressure in the one dog treated. One dog died of gastric perforation 10 days after lasering, but no other animal experienced any ill effects. These findings may have therapeutic implications for the management of esophageal reflux. PMID- 2227314 TI - Endoscopic retrograde cannulation of the gallbladder: direct dissolution of gallstones. AB - Percutaneous transhepatic catheterization of the gallbladder for dissolution of cholesterol stones by instillation of methyl tert-butyl ether (MTBE) is an invasive therapeutic procedure. The only non-invasive alternative available to now, endoscopic retrograde cannulation of the cystic duct, was difficult because of the cystic duct's tortuosity and spiral valves. We therefore developed a catheter system which, using conventional duodenoscopes during a routine endoscopic retrograde cholangiography (ERC) procedure, permits reliable and safe catheterization of the gallbladder without the need for endoscopic sphincterotomy. In 18 of 22 patients (82%) we were able to place a cysto-nasal catheter, and in 14 patients MTBE dissolution therapy was then performed. Eight patients (57%) were completely free of stones after treatment; the other six (43%) had residual debris. In 4 of 22 patients (18%) cannulation attempts failed, in 3 patients due to cystic duct blockage by a calculus. Endoscopic retrograde cannulation of the gallbladder (ERCG) represents a promising alternative to the invasive percutaneous transhepatic catheterization procedure. PMID- 2227315 TI - Pain on common bile duct injection during ERCP: does it indicate sphincter of Oddi dysfunction? AB - The reproduction of a patient's biliary-type pain upon initial injection of contrast material into the common bile duct during diagnostic ERCP is a dramatic experience for both patient and physician. The significance of this phenomenon is not clear, but it is touted by some to be a provocative test for sphincter of Oddi dysfunction. Sphincter of Oddi manometry was performed on 224 consecutive patients referred over a 2-year period for evaluation of post-cholecystectomy syndrome and suspected sphincter of Oddi dysfunction. All patients received only intravenous diazepam as premedication for ERCP. Delayed drainage time (greater than 45 min), bile duct dilation (greater than or equal to 12 mm), and a basal sphincter of Oddi pressure of greater than 40 mm Hg (mean +/- 3 SD) were considered elevated. We observed a reproduction of pain in 15 of 224 patients (6.7%) immediately following contrast injection. There was no correlation between pain on contrast injection and elevated basal sphincter of Oddi pressure, delayed common bile duct drainage, bile duct dilation, or abnormal liver enzymes. Therefore, we feel that reproduction of the patient's biliary-type pain associated with contrast injection of ERCP is not a provocative test for sphincter of Oddi dysfunction. PMID- 2227317 TI - The role of endoscopic injection sclerotherapy in the management of bleeding peristomal varices. AB - Peristomal varices usually occur in patients with enterostomies who develop portal hypertension, and represent a cause of recurrent or intractable gastrointestinal bleeding. Treatment options for such bleeding include surgical ligation of varices, stoma revision with devascularization, injection sclerotherapy, portacaval shunt, or liver transplantation. We reviewed the records of seven patients with peristomal varices, who were followed for a mean of 17 months after diagnosis. Fourteen episodes of clinically significant peristomal bleeding occurred in six patients. Surgical ligation of varices was ineffective in controlling bleeding in two of three patients, although stoma revision with devascularization was temporarily effective in two other patients. Injection sclerotherapy, used in three patients, effectively controlled acute bleeding without serious complications or need for surgery. Definitive treatment for peristomal bleeding (portacaval shunt or liver transplantation) has prevented any further bleeding in three patients for a mean of 8 months after surgery. PMID- 2227316 TI - Sincalide-aided ultrasonography of the common bile duct as a predictor of biliary obstruction determined by ERCP and biliary manometry. AB - Sonographically observed changes in common bile duct caliber following intravenous sincalide injection were correlated with distal common duct pathology as defined by endoscopic retrograde cholangiopancreatography and biliary manometry. Thirty-two patients, 17 with prior cholecystectomies, were studied. In post-cholecystectomy patients, a 1-mm or greater diminution of duct caliber within 5 min represented a normal response. When gallbladder contraction occurred in normal patients with an intact gallbladder, no change or a diminution in duct caliber was observed. When gallbladder contraction was not observed, a normal response was considered to be the same as that in post-cholecystectomy patients with a diminution in duct caliber occurring. By using these criteria two false negatives, both with hypertensive sphincters of Oddi that responded normally to sincalide injection, were encountered. This technique was valuable in defining non-obstructed post-cholecystectomy dilated bile ducts which demonstrated a prompt diminution in caliber following sincalide injection. PMID- 2227318 TI - Variceal sclerosis in schistosomotic patients: a 5-year follow-up study. AB - To assess the therapeutic possibilities of injection sclerosis in schistosomotic portal hypertension, a 5-year prospective study was conducted in northeast Brazil, where this parasitosis is endemic. Fifty patients undergoing endoscopy for upper gastrointestinal hemorrhage from rupture of esophageal varices from July through December 1981 were chosen for the study. The 32 consenting patients were submitted to injection sclerotherapy paravariceally, using ethanolamine oleate; the 18 refusing to participate were assigned to the control group. The incidence of rebleeding was 28.1% in the former and 44.5% in the latter, a difference which was not statistically significant (Fisher's test, p = 0.375). Mortality from rupture of esophageal varices was 3.1% in the sclerotherapy group and 27.7% in the control group, a statistically significant difference (Fischer's test, p = 0.017). Since sclerotherapy markedly improved the long-term survival rate of the patients, this procedure is advocated for the treatment of esophageal varices in cases of portal hypertension due to schistosomiasis. PMID- 2227319 TI - Schatzki's ring: long-term results following dilation. AB - The purpose of this study is to report long-term results of 61 patients with Schatzki's ring who were dilated for relief of dysphagia. The severity of Schatzki's ring was mild in 28 patients (46%), moderate in 26 (43%), severe in 5 (8%), and indeterminate in 2 (3%). Follow-up information was available in 56 of 61 patients (mean, 75 months). During follow-up, 35 patients (63%) developed recurrent dysphagia and required repeated dilations: 19 patients (34%) had one to two dilations, 9 patients (16%) had three to seven dilations, 6 patients (11%) had more than seven dilations; 1 patient underwent surgery for resection of the Schatzki's ring (2%). The mean (range) dilation-free interval was 50.1 months (11.8 to 100 months) in mild cases, 44.5 months (8.9 to 82 months) in moderate cases, and 28.6 months (9 to 76 months) in severe cases. There was no significant correlation between the severity of Schatzki's ring on initial presentation and the subsequent dilation-free interval. Our data indicate that recurrent dysphagia is common among patients with Schatzki's ring after a successful dilation, and that the severity of Schatzki's ring is not a good prognostic indicator of the need for subsequent dilation. PMID- 2227320 TI - Witzel pneumatic dilation for achalasia: safety and long-term efficacy. AB - Forceful dilation of the lower esophageal sphincter is considered primary therapy for achalasia. The Witzel pneumatic balloon dilator, unlike fluoroscopically placed dilators, is placed over a standard gastroscope allowing positioning and dilation under direct vision. We report our experience with the Witzel dilator in 45 patients with achalasia over a 5-year period. All patients had at least one major symptom score of 8 out of 10 for dysphagia and/or regurgitation before dilation. After Witzel dilation, symptomatic response was graded as excellent (score 0 to 2), good (score 3 to 5), fair (score 6 to 8), and poor (no improvement). Symptom response was assessed after 1 week, 1 month, 6 month, 1 year, and present. The mean period of follow-up was 25 months (range, 3 to 85 months). Passage of the balloon across the gastroesophageal junction was technically unsuccessful in three patients. Esophageal perforation occurred in two patients (4%) and transient chest pain greater than 2 days in three patients (7%). There was no bleeding or death. Symptomatic long-term improvement was excellent in 25 patients (63%), good in 6 patients (15%), fair in 4 patients (10%), and poor in 5 patients (12%). A repeat Witzel dilation was performed in five patients but resulted in good/excellent improvement in only one patient. We conclude that pneumatic dilation with the Witzel balloon is a safe, effective procedure for achalasia. PMID- 2227321 TI - Performing screening flexible sigmoidoscopy using colonoscopes: experience in 500 subjects. AB - There is still controversy regarding the optimal length of flexible sigmoidoscopes. We performed screening distal colon examinations using 168-cm colonoscopes in 500 asymptomatic subjects who were unsedated and had sigmoidoscopy cleansing preparation. The mean depth of penetration was 66 cm and was similar in persons in whom the examination was discontinued because of poor preparation versus those with discomfort. Polyps were detected in 87 patients, but only 5 subjects had polyps detected above 60 cm. We conclude that in a group of unsedated subjects scheduled for flexible sigmoidoscopy after a sigmoidoscopy prep, the use of instruments longer than 60 cm gives very little additional yield. PMID- 2227322 TI - Arterial blood oxygen desaturation in infants and children during upper gastrointestinal endoscopy. AB - Arterial blood oxygen desaturation and abnormal electrocardiographic changes have been reported in adults undergoing upper gastrointestinal endoscopy. We studied 32 infants and children less than 12 years of age using pulse oximetry and continuous electrocardiography before, during, and after upper gastrointestinal endoscopy performed under intravenous sedation. Sinus tachycardia was the most common electrocardiographic change, and no clinically significant electrocardiographic abnormalities were induced by the procedure. Desaturation to less than or equal to 90% was found in 37.5% of the patients and was most commonly noted during the endoscopy procedure and in patients with cardiopulmonary disease. The desaturation was unpredictable because there was no correlation between desaturation and medication, tolerance to the procedure, weight, or age of the child. Some patients who subjectively appeared to tolerate the procedure well had significant desaturation. The use of pulse oximetry should be considered for all children undergoing upper gastrointestinal endoscopy. PMID- 2227323 TI - First clinical evaluation and experimental study of a new mechanical suture device for endoscopic hemostasis. PMID- 2227324 TI - A method to correlate common bile duct pressure and the migrating motor complex of the duodenum. PMID- 2227325 TI - Does continuous aspiration from an end and side port in a sphincter of Oddi manometry catheter alter recorded pressures? PMID- 2227326 TI - Endoscopic biliary decompression aided by a different technique of percutaneous transhepatic access. PMID- 2227327 TI - Submucosal tumors of the terminal ileum managed by endoscopic polypectomy. PMID- 2227328 TI - Endoscopic correction of intussusception and removal of a colonic lipoma. PMID- 2227329 TI - Endoscopic diagnosis and treatment of duodenal gastrinoma. PMID- 2227330 TI - An unusual vascular lesion in a patient with hereditary hemorrhagic telangiectasia. PMID- 2227331 TI - The honeycomb stomach: coalesced gastric angiodysplasia. PMID- 2227333 TI - Endoscopic transpapillary drainage of gallbladder empyema. PMID- 2227332 TI - ERCP documentation of obstructive jaundice caused by a solitary, centrally located, benign hepatic cyst. PMID- 2227334 TI - Endoscopic removal of an intact anti-reflux prosthesis 6 years after implantation. PMID- 2227335 TI - Endoscopic removal of toothbrushes. PMID- 2227336 TI - Use of endoscopic laser therapy to prevent reflux. PMID- 2227337 TI - The cystic artery: borderline between internal medicine and surgery? PMID- 2227338 TI - Delayed hemorrhage after hot biopsy. PMID- 2227339 TI - Modify technique for wire-guided papillotomy. PMID- 2227340 TI - Endoscopic extraction of a proximally migrated Amsterdam-type biliary endoprosthesis. PMID- 2227341 TI - Malignant obstructive jaundice. PMID- 2227342 TI - Sclerotherapy and corticosteroids: a word of caution. PMID- 2227343 TI - More on the tip of the therapeutic video duodenoscope. PMID- 2227344 TI - Seeing red. PMID- 2227345 TI - Monitoring during endoscopy. PMID- 2227346 TI - Endoscopic diagnosis of intestinal metaplasia. PMID- 2227347 TI - Infective endocarditis and infections of orthopedic and vascular prostheses following gastrointestinal endoscopy and dilation. PMID- 2227348 TI - Nucleotide sequence of the G6-amylase gene from alkalophilic Bacillus sp. H-167. AB - The nucleotide sequence of the G6-amylase gene from alkalophilic Bacillus sp. H 167 was determined. The open reading frame of the gene consisted of 2865 base pairs, encoding 955 amino acids. The NH2-terminal amino acid sequence analysis of the G6-amylase indicated that the enzyme had a single peptide of 33 amino acid residues and the mature enzyme was composed of 922 amino acids, giving a molecular mass of 102,598. Identity of the NH2-terminal amino acid sequences among each component of the multiform G6-amylase suggested the proteolytic processing of the COOH-terminal side of the enzyme. The DNA sequence and the deduced amino acid sequence of the G6-amylase gene showed no homology with those of other bacterial alpha-amylases although the consensus amino acid sequences of the active center were well conserved. PMID- 2227349 TI - Isolation of zidovudine resistant Escherichia coli from AIDS patients. AB - Zidovudine-resistant Escherichia coli were isolated from faecal samples from 6 out of 11 AIDS patients receiving zidovudine. Resistance appeared to be due to the loss of thymidine kinase activity which is required for the phosphorylation of zidovudine to its active form. No zidovudine resistant enterobacteria were isolated from 30 control faecal samples. Hence, clinically, there appeared to be a high correlation between the development of zidovudine-resistance in E. coli and exposure to zidovudine (chi 2: 11.77, P less than 0.001). However the development of zidovudine resistance does not appear to be associated with cross resistance to other antimicrobial agents as the zidovudine-resistant E. coli did not display a high degree of resistance to other antibacterials. PMID- 2227350 TI - Effect of coumarin on glucose uptake by anaerobic rumen fungi in the presence and absence of Methanobrevibacter smithii. AB - The effect of coumarin (1,2 benzopyrone) on glucose utilisation by the anaerobic rumen fungi Neocallimastix frontalis and N. patriciarum has been compared with the effect of p-coumaric acid. Both compounds largely inhibited glucose utilisation by N. patriciarum strain Cx when present in the medium at a concentration of 2.5 mM, and had a similar effect on N. frontalis strain RE1 at 5 mM. Although in earlier studies co-culturing rumen fungi with Methanobrevibacter smithii enhanced resistance to ionophores, no comparable protective effect of M. smithii was found in the present study. PMID- 2227351 TI - Evidence that the capsule around mycobacteria grown in axenic media contains mycobacterial antigens: implications at the level of cell envelope architecture. AB - The intracellular growth of pathogenic mycobacteria has been linked to the presence of an electron transparent zone (ETZ or capsule), which surrounds the phagocytized bacteria and prevents the diffusion of lysosomal enzymes in infected macrophages. Recently, it was suggested that this capsule may be a bacterial structures, even being present in test tube-grown pathogenic mycobacteria (FEMS Microbiol. Lett. 1988, 56, 225-230). In the present paper, we show that under special fixation and embedding conditions, this capsule was clearly observed among 7 strains of mycobacteria grown in axenic media and also in M. leprae extracted and purified from experimentally infected armadillo or nude mice. In the case of bacteria treated likewise but subject to a prior dehydration step, this capsular structure disappeared suggesting its lipidic nature. Ultrathin sections of M. intracellular after immunolabelling showed for the first time that this capsule obtained mycobacterial antigens confirming its mycobacterial origin. It is suggested that the mycobacterial capsule may be formed of inert lipids, in which surface antigens are embedded. PMID- 2227352 TI - Induction of vancomycin resistance in Enterococcus faecium by inhibition of transglycosylation. AB - Vancomycin resistance has recently been recognized among clinical isolates of enterococci. Resistance is inducible, and associated with production of a novel 39 kDa membrane protein. The mechanism by which exposure to vancomycin, which does not penetrate the cell membrane, induces resistance is unknown. In the vancomycin resistant strain Enterococcus faecium 228, resistance was also inducible by moenomycin, suggesting that inhibition of the transglycosylation step in peptidoglycan synthesis may be required for induction of resistance. Cytoplasmic pools of peptidoglycan precursors were increased after exposure to vancomycin or moenomycin, representing a potential means for regulation of induction. PMID- 2227353 TI - Anaeromyces mucronatus nov. gen., nov. sp. A new strictly anaerobic rumen fungus with polycentric thallus. AB - A new species of strictly anaerobic fungus was isolated from the cow rumen. It is characterized by a polycentric thallus, a polynuclear rhizomycelium, mucronate zoosporangia and uniflagellated zoospores. It is also singular in that the sporocysts do not react to the specific lectins of L-fucose, N-acetyl-D galactosamine and diacetyl chitobiose. These characteristics justify the creation of a new genus. PMID- 2227354 TI - Evidence for two fatty alcohol oxidases in the biosurfactant-producing yeast Candida (Torulopsis) bombicola. AB - Fatty alcohol oxidase activities in Candida (Torulopsis) bombicola ATCC 22214, which produces large amounts of glycolipids consisting of omega- and (omega-1) hydroxyfatty acids and a sugar moiety, occurred only in the microsomal fraction whether the cells had grown on n-alkanes, carbohydrates or a mixture of the two. High activities occurred in glucose-grown cells. Aliphatic alcohols from octanol to hexadecanol were oxidized with two maxima in activities for decanol and for tetradecanol. Differences in their pH optima and in temperature stability suggest two separate enzymes are present. Long chain diols, but not omega-hydroxyfatty acids, were also oxidized. PMID- 2227355 TI - Assay of 4-hydroxybutyryl-CoA dehydratase from Clostridium aminobutyricum. AB - It has been proposed that Clostridium aminobutyricum contains an enzyme catalyzing an unusual reaction: the dehydration of 4-hydroxybutyryl-CoA to vinylacetyl-CoA. 4-Hydroxy-[3-3H]butyric acid has been prepared which allows the activity of this enzyme to be assayed in the presence of acetyl-CoA under anaerobic conditions by the release of tritiated water. Initial characterization of the enzyme from C. aminobutyricum has shown it to be largely membrane or particle bound in the crude lysates. It can be solubilized in detergent. It is inactivated by oxygen, but stable under anaerobic conditions. Only 49 +/- 2% of the label is removed after enzyme-catalyzed equilibration with water. This stereospecific release is consistent with the formation of vinylacetyl-CoA and excludes a vitamin B12 coenzyme-dependent rearrangement to 3-hydroxybutyryl-CoA followed by dehydration to crotonyl-CoA. PMID- 2227356 TI - The invasiveness of different strains of Salmonella enteritidis phage type 4 for young chickens. AB - Five strains of Salmonella enteritidis phage type 4 (PT4) isolated in 1978, 1984 and 1988 were examined for their ability to colonise the caecum and invade the liver of day-old chickens. All strains were capable of caecal colonisation and there were no differences in their colonisation ability in this respect. In contrast there was a gradation in the ability of strains to invade the liver, with strains isolated in 1988 proving the most invasive. Absence of a 38 megadalton (Md) plasmid, which has been shown to be involved in the virulence of S. enteritidis PT4 for BALBc mice, had little effect on the ability of strains of this phage type to colonise the caecum or invade the liver of day-old chickens. These results suggest that recent isolates of PT4 may have enhanced virulence for chickens which is not necessarily associated with the carriage of a 38 Md plasmid. PMID- 2227357 TI - Starvation-induced modulations in binding protein-dependent glucose transport by the marine Vibrio sp. S14. AB - The uptake kinetics of D-glucose were examined in the marine Vibrio sp. S14 during a period of 168 h of complete energy and nutrient starvation. Two glucose transport systems were distinguished in Vibrio sp. S14: a low affinity system (Km = 4.6 +/- 0.9 microM) at the onset of starvation, and a high affinity system (Km = 0.55 +/- 0.15 microM) after 168 h of starvation. Both systems had a narrow substrate specificity, and both were osmotic shock-sensitive. PMID- 2227358 TI - Factors involved in the electroporation-induced transformation of Clostridium perfringens. AB - The following factors were found to improve the efficiency of transformation of Clostridium perfringens 3624A Rifr Strr: (1) a reduction in cuvette sample volume (DNA and cell suspension) to 0.8 ml, (2) use of a 1 microgram/ml concentration of transforming DNA, (3) use of late-logarithmic phase cells, (4) 3-fold concentration of cell density (3.0 x 10(8) CFU/ml), and (5) a reduction in the pH of the expression and selective plating medium to 6.4. Application of the improved conditions resulted in transformation efficiencies for C. perfringens 3624A Rifr Strr ranging from 7.1 transformants/microgram DNA for plasmic pIP401 to 9.2 x 10(4) transformants per microgram DNA for plasmid pAK201. The greatest transformation efficiency obtained using pAK201 was 9.8 x 10(6) transformants/micrograms DNA for C. perfringens strain 13. Using the improved protocol, pAM beta 1 was transformed at a 42-fold greater level when compared with the values reported earlier [1]. In addition to C. perfringens 3624A Rifr Strr, strains 13, 10543A, 3628C, NTG-4, and 3624A were successfully transformed. Nuclease does not appear to be a factor in the C. perfringens strain-specific electro-transformation protocol. PMID- 2227359 TI - Cloning and expression of the carbon monoxide dehydrogenase genes from Pseudomonas thermocarboxydovorans strain C2. AB - Carbon monoxide dehydrogenase (CODH) from Pseudomonas thermocarboxydovorans strain C2 is composed of three non-identical subunits. A gene library of C2 DNA in lambda vector L47.1 was generated and screened using anti-CODH serum. Western blotting experiments revealed a protein which co-migrated with and had the same immunological reaction as the large subunit of CODH in some of the clones isolated from the library. The coding region was pinpointed to a 4 kb fragment which was subcloned into plasmid. Western blotting experiments showed that all three subunits of CODH were coded for by the subclone. However, no CODH activity was detected. PMID- 2227360 TI - The phylogeny of Aerococcus and Pediococcus as determined by 16S rRNA sequence analysis: description of Tetragenococcus gen. nov. AB - The phylogenetic interrelationships of the genera Pediococcus and Aerococcus were investigated using reverse transcriptase sequencing of 16S rRNA. The genus Pediococcus was found to be phylogenetically heterogeneous. The four species P. acidilactici, P. damnosus, P. parvulus and P. pentosaceus formed a phylogenetically distinct group. Within this pediococcal cluster, P. acidilactici was closely related to P. pentosaceus whereas P. damnosus showed a specific relationship with P. parvulus. The species P. dextrinicus, although showing significant sequence relatedness with these pediococcal species, was peripheral to the genus. Pediococcus halophilus exhibited low sequence homology with all of the species examined and formed a distinct line of descent. Pediococcus halophilus exhibited a closer affinity with enterococci and carnobacteria than with the other lactic acid bacteria. Pediococcus urinae-equi was phylogenetically very closely related to Aerococcus viridans. The 16S rRNA sequences of the type strains of these species differed by only two nucleotides (99.9% sequence homology) and clearly demonstrate that P. urinae-equi is a member of the genus Aerococcus. PMID- 2227361 TI - Analysis of immune response: comparison of immunoblots after isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis using cytoplasmic protein extract from Brucella. AB - Analysis of the immune response towards the facultative intracellular bacterium, Brucella melitensis, was studied by immunoblotting after either isoelectric focusing (IEF) or sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE). A cytoplasmic extract (CPE) of Brucella melitensis was used as antigen to analyse the response in 17 sera from naturally infected goats. CPE analysed by IEF exhibited 25 proteins within the pH range of 4.35 to 6. Immunoblotting revealed most of the stained bands around pH 4.5-5.4. CPE analysed by SDS-PAGE showed more than 20 silver stained proteins in the molecular range of 16-18 kDa to 70 kDa but immunoblotting revealed only 1 to 6 bands according to the sera tested. Because proteins are preserved in their native state with IEF, in contrast to SDS-PAGE treatment, this technique may be best suited for analysis of the overall response to natural infection. PMID- 2227362 TI - Antimicrobial effect of human milk on Bordetella pertussis. AB - It has been demonstrated that human milk, unlike bovine milk, can reduce the viability of Bordetella pertussis. This antibacterial activity was not due to the presence of antibiotics or antibodies in the human milk. Reducing the level of available iron or increasing the concentration of lysozyme in bovine milk did not induce anti-B. pertussis activity. Analysis of total fatty acids revealed that human milk contained significantly more linoleic acid than bovine milk. However, the addition of linoleic acid to bovine milk did not inhibit the growth of B. pertussis. PMID- 2227363 TI - Factors and markers of virulence in Escherichia coli from human septicemia. AB - One hundred Escherichia coli isolates from human septicemia were characterized with respect to O serogroups 1, 2, 4, 6, 7, 8, 15, 18, 75 and 78, alpha hemolysin, carboxylesterase B typing, cytotoxic necrotizing factor, F165 and CS31A fimbrial antigens, aerobactin production, colicins, and antibiotic sensitivity. A factorial analysis of correspondence and chi 2 tests indicated that most of E. coli isolates belonging to the studied O serogroups were positive for the virulence factors or markers alpha-haemolysin, carboxylesterase B2 type, cytotoxic necrotizing factor, F165 fimbrial antigen and were antibiotic-sensitive (Group I). These characteristics differentiated them from E. coli isolates from other O serogroups which were generally antibiotic resistant and negative for the cited virulence factors and markers (Group II). Aerobactin and colicin production did not differentiate the two E. coli groups. E. coli O serogroups 4 and 6 were highly represented in group I and were responsible for most of the differences between the two groups. PMID- 2227364 TI - Nucleotide sequence of the Serratia marcescens SR50 chromosomal ampC beta lactamase gene. AB - The Serratia marcescens SR50 chromosomal beta-lactamase gene (ampC) was cloned and sequenced. It contains 1128 nucleotides encoding a protein of 355 amino acids preceded by 21 amino acids which probably constitutes the signal peptide. The mature protein has a predicted molecular mass of 38,901 Da. About 40% of the amino acid sequence was identical among AmpC beta-lactamases resided in S. marcescens, Citrobacter freundii OS60, Escherichia coli K12 and Enterobacter cloacae P99. All of these enzymes are highly similar around the active site serine at the position 59 of the mature enzyme. PMID- 2227365 TI - Evaluation of cytotoxic activity in fecal filtrates from patients with Campylobacter jejuni or Campylobacter coli enteritis. AB - We sought to determine the prevalence of cytotoxic activity in fecal filtrates from persons with C. jejuni or C. coli enteritis. Stool specimens were collected from 20 persons with C. jejuni or C. coli enteritis, 20 persons with acute diarrheal illnesses of other causes, and 9 healthy, asymptomatic persons. Fecal filtrates were then incubated with Chinese hamster ovary (CHO) or HeLa cells. The fecal filtrate from 1 of the 20 (5%) persons with Campylobacter enteritis was cytotoxic for HeLa cells at a titer of 1:40, and 10 (50%) were cytotoxic for CHO cells at maximum titers of 1:20. Cytotoxic activity for CHO cells at a median titer of 1:20 was also present in 40% of the fecal filtrates from persons with diarrhea due to causes other than Campylobacter enteritis, and in 33% of filtrates from healthy, asymptomatic persons. The observed low level of cytotoxicity in fecal filtrates from all patient groups studied likely resulted from non-specific factors, unrelated to the pathogenesis of Campylobacter enteritis. PMID- 2227367 TI - Stability of soluble and extracellular vesicle-associated trypsin-like protease (TLP) activity of Bacteroides gingivalis W50. AB - Comparison was made of the specific activities of whole extracellular soluble protein (EP) and extracellular vesicle (ECV)-associated trypsin-like protease (TLP) activity from batch cultures of Bacteroides gingivalis W50. Rapid loss of activity occurred when these fractions were maintained at 37 degrees C in the presence of DTT. Residual levels of activity were detected after incubation of ECV and EP for up to 8 days under non-reducing conditions. Rates of activity loss in EP and ECV were similar. Mixtures of EP and ECV, in the same proportions as found in the culture supernatant showed neither depression nor elevation of total activity from the expected compound activities of the two separate fractions. PMID- 2227366 TI - Simultaneous exploitation of different peptide permeases by combinations of synthetic peptide smugglins can lead to enhanced antibacterial activity. AB - Various synthetic, peptide prodrugs (smugglins) were tested alone and in combination for activity against Escherichia coli. The smugglins may be transported through any of three peptide permeases, and once inside the bacteria are activated by intracellular peptidase action to release their intrinsically impermeant, antibacterial moieties. When each such antibiotic peptide present in a mixture was accumulated via a different permease, synergistic effects could be observed. Synergy was also found when smugglins were combined with other non peptide antibiotics. The principle of using smugglin combinations could extend the scope of their application, and should minimise the potential problem that can arise from the occurrence of resistant, transport mutants. The smugglin interactions were studied using a modified microtitre plate assay. PMID- 2227368 TI - Determination of taxonomic resolution capacity of conventional one-dimensional SDS-polyacrylamide gel electrophoresis of whole-cell proteins using Enterobacteriaceae. AB - The capacity of one-dimensional SDS-PAGE of whole bacterial cells to both separate and cluster taxonomic units is studied using members of Enterobacteriaceae as test material. The results show that intraspecies variation can be detected and on the other hand the degree of taxonomic divergence which still can be grouped together is determined. In addition the system has high tolerance to changes in cell culture conditions making the usage of SDS-PAGE suitable for applications where rapid and reliable bacterial identification is needed. PMID- 2227370 TI - Measuring the inflation of the lod score due to its maximization over model parameter values in human linkage analysis. AB - A computer-simulation method is presented for determining and correcting for the effect of maximizing the lod score over disease definitions, penetrance values, and perhaps other model parameters. The method consists of simulating the complete analysis using marker genotypes randomly generated under the assumption of free recombination. It is applicable as a "post-treatment" to linkage analyses of any trait with an uncertain mode of inheritance and/or disease definition. When the method is applied to a linkage analysis of schizophrenia versus chromosome 5 markers, we find that, in this specific case, the P-value associated with a maximum lod score of 3 is equal to 0.0003. We also find that a lod score of 3.0 should be "deflated" by approximately 0.3 to 1 units, and, by tentative extrapolation, the observed lod score of 6.5 should be "deflated" by 0.7 to 1.5 units. PMID- 2227369 TI - Digestion of human immunoglobulin G by the major cysteine proteinase (cruzipain) from Trypanosoma cruzi. AB - The major cysteine proteinase (cruzipain) from Trypanosoma cruzi was able to digest human IgG, as shown by polyacrylamide gel electrophoresis in the presence of SDS, and by gel filtration on a Superose 12 column, in a FPLC system. The Fab fragment of IgG was only slightly degraded, but Fc was extensively hydrolyzed to small peptides. The results suggest that cruzipain might be involved in the defense mechanisms of the parasite against the immune response of the host. PMID- 2227371 TI - Assessing the effect of multiple linkage tests in complex diseases. AB - The significance of a lod score value of 3 is very difficult to assess in linkage studies between a genetic marker and a complex disease. One reason is that multiple tests may have been performed, voluntarily or otherwise. For the same disease, linkage may be tested by different laboratories with several markers under various genetic models and diagnostic schemes for the disease. In such a case, we show that the probability of getting a lod score value of 3 under independent transmission of the disease and the marker may be not negligible. PMID- 2227372 TI - Structure of ischemic heart disease risk factors in the North Khanty population of western Siberia. AB - The relationships between serum lipids, blood pressures, anthropometric traits, age, and ischemic changes of the electrocardiogram (ECG) in the North Khanty population were studied. To this end, eight morphophysiological variables- presumably risk factors for ischemic heart disease--have been subjected to a principal components analysis. Two principal components were extracted. The first revealed age dependency of the traits not associated with ischemic changes of myocardium in both sexes. A comparative analysis of the second component has shown that the chosen traits correlated with ischemic heart disease in males but not in females. Interpretation is given of the components obtained. PMID- 2227373 TI - Twin concordance for a binary trait: III. A bivariate analysis of hay fever and asthma. AB - Self-reported histories of hay fever and asthma were obtained from 3,808 pairs of adult twins 18 years and over registered with the Australian National Health Medical Research Council Twin Registry (1232 MZF, 567 MZM, 751 DZF, 352 DZM, 906 DZO). The prevalence of hay fever and asthma was 0.32 and 0.13, respectively, with little variation with zygosity, sex, and age. The associations between twin pairs for these two traits were analysed, under the assumption of constant prevalences, as a special case of a log-linear model for binary traits in pedigrees using the statistical package GLIM. The model assumption that there are no second- or higher-order interactions was tested in the 2 X 2 X 2 X 2 table of twin by disease outcomes without revealing strong evidence of departure, even in this large data set. The log-linear modelling showed that only three first-order interactions, namely 1) between hay fever in a twin pair, 2) asthma in a twin pair, and 3) hay fever and asthma in the same twin, were necessary to describe the data. The first two interaction terms were significantly larger in identical pairs; the third was independent of zygosity. Under this parsimonious model, there was a significant difference between identical and fraternal pairs in marginal correlation, both in asthma and hay fever, and in the cross-correlation between hay fever in one twin and asthma in the other. This suggests that genetic factors are implicated in both hay fever and asthma and that some of these genetic factors are common (at least among a subgroup of individuals) to both traits. PMID- 2227374 TI - Familial factors associated with malignant gliomas. AB - Family histories of male patients with histologically confirmed malignant gliomas were compared to family histories of controls (wives). Included were 77 case families with 892 relatives and 77 control families with 719 relatives. Cases had significantly more siblings than controls (P = 0.02), although cases were not preferentially the oldest or the youngest sibs. Odds ratios of two or more were found for mental retardation, Parkinson's disease, and meningitis for the relatives of cases versus controls, but none were statistically significant. The excesses of Parkinson's disease and meningitis were explained by the family of one particularly interesting case containing three relatives with meningitis and two relatives with Parkinson's disease. Noteworthy age-adjusted odds ratios for cancer among relatives of cases compared to relatives of controls were 1.6 (95% confidence interval (CI) = 1.0-2.3) for cancer of any site, 2.4 (95% CI = 0.8 6.1) for breast cancer, and 4.0 (95% CI = 0.6-10.7) for lung cancer. Only the odds ratio for cancer of any site was statistically significant. Overall, 6 of 77 (8%) of cases came from families that included two or more relatives with breast or lung cancer in addition to the proband with malignant glioma. These three cancer sites may form familial clusters worthy of further evaluation in future studies by pedigree and genetic linkage analyses. PMID- 2227375 TI - Association of Duffy blood group with schizophrenia in Chinese. PMID- 2227376 TI - Information theory and collative motivation: incentive value of uncertainty, variety, and novelty for children. AB - We tested the applicability of concepts and measures from information theory to studies of the development and operation of collative motivation. Three variables nominated by Berlyne as potential motivators of information seeking--uncertainty, variety, and novelty--were put into correspondence with three informational theoretic measures--average uncertainty in bits, number of possible outcomes, and outcome probability--to investigate the incentive properties of each variable for first and fourth graders. Increasing bit levels of uncertainty by adding alternatives to the set of possible outcomes was generally positively related to cover choices; however, increasing bit values by varying outcome probabilities from unequal to equal had no effect on choice. Without uncertainty, variety provided a weak source of collative motivation, systematically related to the choice of the transparent cover only for the older children when rewards occurred equally frequently. In contrast, the transparent cover was chosen significantly more frequently when the outcome probability of the associated reward was low. We obtained developmental stability in motivational effects except for variety operating in the absence of uncertainty. PMID- 2227377 TI - Factor structures and validity of the Child-Related Values Survey. AB - The Child-Related Values Survey (CRVS) is being developed for assessment of various values that affect the nature of our regard for the psychological and physical welfare of children in general. Factor analysis of the CRVS resulted in six subscales. A confirmatory factor analysis on these subscales showed that the Affective Valence, Empathic Caring, Self-Sacrifice, and Societies' Duties subscales each reflect a humanitarian concern for children and that the Instrumentality and Authoritarian Attitude subscales tap values involving a moralistic expectation of children. Data on the validity of the CRVS include the humanitarian cluster of subscales predicting subjects' perceived satisfaction in pursuing child-related careers, relating the CRVS to various social issues, and the demonstration of several group differences with respect to CRVS subscales. PMID- 2227378 TI - Herschel L. Roman (1914-1989). PMID- 2227380 TI - Major effects on teratogen-induced facial clefting in mice determined by a single genetic region. AB - A major correlation has been found between the incidence of glucocorticoid induced cleft palate and the chromosome 8 segment identified by N-acetyl transferase in mice. The resistant strain became fully susceptible while the susceptible strain became resistant when this chromosomal region, representing less than 0.7% of the genome, was transferred from one strain to the other by the construction of congenic strains. 6-Aminonicotinamide-induced cleft palate and phenytoin-induced cleft lip with or without cleft palate are also influenced by this genetic region but not as strongly. In both cases the susceptible strain became quite resistant to the teratogen-induced clefting when the N-acetyl transferase region of chromosome 8 was transferred. However, this chromosomal region does not make the resistant strain susceptible to these two teratogens. PMID- 2227379 TI - Context effects in the formation of deletions in Escherichia coli. AB - We have examined the frequency with which identical deletions are formed in different chromosomal contexts. A panel of six mutant bla genes containing palindrome/direct repeat structures were moved from pBR322 to three locations: at lambda att, at chromosomal lac, and at F'lac. Deletion of the palindromes and one of the direct repeats results in reversion to Ampr. The frequency of deletion for all alleles declines beyond the reduction in copy number when they are moved from the multicopy plasmid environment to a single-copy chromosome. The magnitude of the declines varies in an allele-specific and location-specific manner. Our data support the hypothesis that context can influence the frequency of mutation independent of the immediate DNA sequence. PMID- 2227381 TI - Theoretical study of near neutrality. I. Heterozygosity and rate of mutant substitution. AB - In order to clarify the nature of "near neutrality" in molecular evolution and polymorphism, extensive simulation studies were performed. Selection coefficients of new mutations are assumed to be small so that both random genetic drift and selection contribute to determining the behavior of mutants. The model also incorporates normally distributed spatial fluctuation of selection coefficients. If the system starts from "average neutrality," it will move to a better adapted state, and most new mutations will become "slightly deleterious." Monte Carlo simulations have indicated that such adaptation is attained, but that the rate of such "progress" is very low for weak selection. In general, the larger the population size, the more effective the selection becomes. Also, as selection becomes weaker, the behavior of the mutants approaches that of completely neutral genes. Thus, the weaker the selection, the smaller is the effect of population size on mutant dynamics. Increase of heterozygosity with population size is very pronounced for subdivided populations. The significance of these results is discussed in relation to various observed facts on molecular evolution and polymorphism, such as generation-time dependency and overdispersion of the molecular clock, or contrasting patterns of DNA and protein polymorphism among some closely related species. PMID- 2227382 TI - Relationship between migration and DNA polymorphism in a local population. AB - The expected amount of DNA polymorphism, measured in terms of the number of nucleotide differences between the two DNA sequences randomly sampled from subpopulations, was studied by using the stepping-stone model and the finite island model, under the assumption that the migration rate is not the same among different subpopulations. The results obtained indicate that the expected amount of DNA polymorphism in the subpopulation with lower migration rate is smaller than that of higher migration rate. This suggests that marginal populations tend to have lower level of DNA polymorphism than central populations if the migration rate in the marginal populations is lower than that of the central populations. PMID- 2227384 TI - Detecting isolation by distance using phylogenies of genes. AB - We introduce a method for analyzing phylogenies of genes sampled from a geographically structured population. A parsimony method can be used to compute s, the minimum number of migration events between pairs of populations sampled, and the value of s can be used to estimate the effective migration rate M, the value of Nm in an island model with local populations of size N and a migration rate m that would yield the same value of s. Extensive simulations show that there is a simple relationship between M and the geographic distance between pairs of samples in one- and two-dimensional models of isolation by distance. Both stepping-stone and lattice models were simulated. If two demes k steps apart are sampled, then, s, the average value of s, is a function only of k/(Nm) in a one-dimensional model and is a function only of k/(Nm)2 in a two-dimensional model. Furthermore, log(M) is approximately a linear function of log(k). In a one dimensional model, the regression coefficient is approximately -1 and in a two dimensional model the regression coefficient is approximately -0.5. Using data from several locations, the regression of log(M) on log(distance) may indicate whether there is isolation by distance in a population at equilibrium and may allow an estimate of the effective migration rate between adjacent sampling locations. Alternative methods for analyzing DNA sequence data from a geographically structured population are discussed. An application of our method to the data of R. L. Cann, M. Stoneking and A. C. Wilson on human mitochondrial DNA is presented. PMID- 2227383 TI - How informative is Wright's estimator of the number of genes affecting a quantitative character? AB - S. Wright suggested an estimator, m, of the number of loci, m, contributing to the difference in a quantitative character between two differentiated populations, which is calculated from the phenotypic means and variances in the two parental populations and their F1 and F2 hybrids. The same method can also be used to estimate m contributing to the genetic variance within a single population, by using divergent selection to create differentiated lines from the base population. In this paper we systematically examine the utility and problems of this technique under the influences of unequal allelic effects and initial allele frequencies, and linkage, which are known to lead m to underestimate m. In addition, we examine the effects of population size and selection intensity during the generations of selection. During selection, the estimator m rapidly approaches its expected value at the selection limit. With reasonable assumptions about unequal allelic effects and initial allele frequencies, the expected value of m without linkage is likely to be on the order of one-third of the number of genes. The estimates suffer most seriously from linkage. The practical maximum expectation of m is just about the number of chromosomes, considerably less than the "recombination index" which has been assumed to be the upper limit. The estimates are also associated with large sampling variances. An estimator of the variance of m derived by R. Lande substantially underestimates the actual variance. Modifications to the method can ameliorate some of the problems. These include using F3 or later generation variances or the genetic variance in the base population, and replicating the experiments and estimation procedure. However, even in the best of circumstances, information from m is very limited and can be misleading. PMID- 2227385 TI - Gene conversion, linkage, and the evolution of repeated genes dispersed among multiple chromosomes. AB - The evolution of the probabilities of genetic identity within and between the loci of a multigene family dispersed among multiple chromosomes is investigated. Unbiased gene conversion, equal crossing over, random genetic drift, and mutation to new alleles are incorporated. Generations are discrete and nonoverlapping; the diploid, monoecious population mates at random. The linkage map is arbitrary, but the same for every chromosome; the dependence of the probabilities of identity on the location on each chromosome is formulated exactly. The greatest of the rates of gene conversion, random drift, and mutation is epsilon much less than 1. Under the assumption of loose linkage (i.e., all the crossover rates greatly exceed epsilon, though they may still be much less than 1/2), explicit approximations are obtained for the equilibrium values of the probabilities of identity and of the linkage of disequilibria. The probabilities of identity are of order one [i.e., O(1)] and do not depend on location; the linkage disequilibria are of O(epsilon) and, within each chromosome, depend on location through the crossover rates. It is demonstrated also that the ultimate rate and pattern of convergence to equilibrium are close to that of a much simpler, location-independent model. If intrachromosomal conversion is absent, the above results hold even without the assumption of loose linkage. In all cases, the relative errors are of O(epsilon). Even if the conversion rate between genes on nonhomologous chromosomes is considerably less than between genes on the same chromosome or homologous chromosomes, the probabilities of identity between the former genes are still almost as high as those between the latter, and the rate of convergence is still not much less than with equal conversion rates. If the crossover rates are much less than 1/2, then most of the linkage disequilibrium is due to intrachromosomal conversion. If linkage is loose, the reduction of the linkage disequilibria to O(epsilon) requires only O(-ln epsilon) generations. PMID- 2227386 TI - Two-locus linkage analysis using recombinant inbred strains and Bayes' theorem. AB - Recombinant inbred (RI) strains are useful in linkage analysis and gene mapping. The currently available statistical tests of linkage using data derived from the study of RI strains, including a previous Bayesian analysis, have not been stringent enough guides for conclusions about linkage. In this paper, the probability of linkage was estimated using Bayes' theorem. Tables are presented that give the probability of linkage in sets of up to 30 RI strains and the critical values of i (the number of recombinants) in sets of up to 100 RI strains. Several means of increasing the power of RI strains in linkage analysis are discussed. PMID- 2227387 TI - Genetic control of RNA polymerase I-stimulated recombination in yeast. AB - We examined the genetic control of the activity of HOT1, a cis-acting recombination-stimulatory sequence of Saccharomyces cerevisiae. Mutations in RAD1 and RAD52 decrease the ability of HOT1 to stimulate intrachromosomal recombination while mutations in RAD4 and RAD50 do not affect HOT1 activity. In rad1 delta strains, the stimulation of excisive recombination by HOT1 is decreased while the rate of gene replacement is not affected. In rad52-8 strains the ability of HOT1 to stimulate both excisive recombination and gene replacement is decreased. All of the recombinants in the rad52-8 strains that would be categorized as gene replacements based on their phenotype are diploids apparently derived by endomitosis and excisive recombination. Studies on rad1 delta rad52-8 strains show that these mutations interact synergistically in the presence or absence of HOT1, resulting in low levels of recombination. The rate of gene replacement but not excisive recombination is stimulated by HOT1 in rad1 delta rad52-8 strains. Taken together, the results show that HOT1 stimulates exchange using multiple recombination pathways. Some of the activity of HOT1 is RAD1 dependent, some is RAD52-dependent, and some requires either RAD1 or RAD52 as suggested by the synergistic interaction found in double mutant strains. There is also a component of HOT1 activity that is independent of both RAD1 and RAD52. PMID- 2227388 TI - Spontaneous point mutations that occur more often when advantageous than when neutral. AB - Recent reports have called into question the widespread belief "that mutations arise continuously and without any consideration for their utility" (in the words of J. Cairns) and have suggested that some mutations (which Cairns called "directed" mutations) may occur as specific responses to environmental challenges, i.e., they may occur more often when advantageous than when neutral. In this paper it is shown that point mutations in the trp operon reverted to trp+ more frequently under conditions of prolonged tryptophan deprivation when the reversions were advantageous, than in the presence of tryptophan when the reversions were neutral. The overall mutation rate, as determined from the rates of mutation to valine resistance and to constitutive expression of the lac operon, did not increase during tryptophan starvation. The trp reversion rate did not increase when the cells were starved for cysteine for a similar period, indicating that the increased reversion rate was specific to conditions where the reversions were advantageous. Two artifactual explanations for the observations, delayed growth of some preexisting revertants and cryptic growth by some cells at the expense of dying cells within aged colonies, were tested and rejected as unlikely. The trp+ reversions that occurred while trp- colonies aged in the absence of tryptophan were shown to be time-dependent rather than replication dependent, and it is suggested that they occur by mechanisms different from those that have been studied in growing cells. A heuristic model for the molecular basis of such mutations is proposed and evidence consistent with that model is discussed. It is suggested that the results in this and previous studies can be explained on the basis of underlying random mechanisms that act during prolonged periods of physiological stress, and that "directed" mutations are not necessarily the basis of those observations. PMID- 2227389 TI - Mobility of two optional G + C-rich clusters of the var1 gene of yeast mitochondrial DNA. AB - Yeast mtDNA contains two different kinds of mobile optional sequences, two group I introns and a short G + C-rich insertion to some var1 genes. Movement of each element in crosses has been called gene conversion though little is known about the mechanism of G + C cluster conversion. A new allele of the var1 gene found in mtDNA of Saccharomyces capensis is described that permitted a more detailed comparison between intron mobility and G + C cluster conversion. The S. capensis var1 gene lacks the cc+ element present in all S. cerevisiae var 1 genes and the previously described optional a+ element. In crosses with cc+ a- and cc+ a+ S. cerevisiae strains, both clusters were found to be mobile and, in the latter cross, appear to convert independently and only to homologous insertion sites. No evidence for flanking marker coconversion (a hallmark feature of intron conversion) was obtained despite the availability of nearby physical markers on both sides of cluster conversion sites. These data indicate that G + C cluster conversion has only a superficial resemblance to intron mobility; analogies to procaryotic transposition mechanisms are considered. PMID- 2227390 TI - Isolation and molecular characterization of the Aspergillus nidulans wA gene. AB - The walls of Aspergillus nidulans conidia contain a green pigment that protects the spores from damage by ultraviolet light. At least two genes, wA and yA, are required for pigment synthesis: yA mutants produce yellow spores, wA mutants produce white spores, and wA mutations are epistatic to yA mutations. We cloned wA by genetic complementation of the wA3 mutation with a cosmid library containing nuclear DNA inserts from the wild-type strain. The wA locus was mapped to an 8.5-10.5-kilobase region by gene disruption analysis. DNA fragments from this region hybridized to a 7500 nucleotide polyadenylated transcript that is absent from hyphae and mature conidia but accumulates during conidiation beginning when pigmented spores first appear. Mutations in the developmental regulatory loci brlA, abaA, wetA and apsA prevent wA mRNA accumulation. By contrast, yA mRNA fails to accumulate only in the brlA- and apsA- mutants. Thus, the level of wA transcript is regulated during conidiophore development and wA activation requires genes within the central pathway regulating conidiation. PMID- 2227391 TI - [Genetic determination of spontaneous and induced dominant lethality in Drosophila]. AB - Estimation of heritability ha2 index in experiments on spontaneous and induced dominant lethality gives the possibility to evaluate with sufficient accuracy genetic determination of the effect and its dependence on casual reasons. Besides, the individual breeding method gave quite stable data both on late embryonic lethality index and on heritability value. Directed selection of different test-objects (species or stocks of Drosophila) should be carried out using heritability index, since selection efficiency mostly depends on this value degree. Making stocks resistant and sensitive to certain mutagen classes, their comparison from the point of view of their pharmacogenetic features, on the basis of the indices used, may be taken as the start of studies aimed at further identification of certain biochemical factors or system taking part in manifestation of mutagenic effect. The data obtained permit us to suggest an idea of advisability of studying the genetic control of mutagenesis in humans using the method described. PMID- 2227392 TI - [Polymorphism of the HLA genetic system in Khanty population]. AB - Serological polymorphism of HLA 1 class genes and antigens (A, B, C) was studied in native West-Siberian population of Khants. Genes HLA-A2, A23, A24, B7, B35, B49, Cw4 and Cw7 appeared to be most frequent in this population. HLA-A23/B49 was the most wide-spread haplotype with strong linkage disequilibrium. The main features of the HLA polymorphism indicate profound mongoloid roots of Khants, whereas strong linkage disequilibrium of some HLA alleles confirms the idea of the origin of Khants as a result of ancient mixing of mongoloids and caucasoids. PMID- 2227393 TI - [Gametic disequilibrium in populations of reindeer Chukchi and Asian Eskimos]. AB - Ten local populations of Reindeer Chukchi and four local populations of Asiatic Eskimos were surveyed for variation of nine polymorphic loci (MN, Ss, Cc, Ee, Duffy, AcP, PGM1, Hp, G3M). Pairwise linkage disequilibria were estimated from multilocus genotype frequencies using the Hill's method. Large amounts of linkage disequilibrium were found for the two pairs of linked genes MNSs and CcEe. The same pattern of non-random association between unlinked loci PGM1 and AcP was found in all subpopulations of both tribes that is induced by natural selection. PMID- 2227394 TI - [uvrD-like sequences in the genome of Agrobacterium tumefaciens]. PMID- 2227395 TI - [Cloning of Shigella flexneri 2a genes coding for restriction- modification system Sfl2aI]. AB - The Sfl2aI system of restriction-modification (RM) was revealed in the cells of Shigella flexneri encoded by pKMR114 plasmid belonging to the IncN incompatibility group. The genes for Sfl2aI RM system were cloned. The system was ascribed to the enzymes of the EcoRII specificity, as shown by in vivo and in vitro experiments. Restriction analysis of these genes' region and antigenic properties of the Sfl2aI endonuclease pointed to significant differences between this and EcoRII RM systems. PMID- 2227397 TI - [Development of a system of intragenic mapping for molecular genetic analysis of mutations in the gene LYS2 of Saccharomyces yeasts]. AB - The collection of overlapping lys2 deletions (five in the chromosomal and seven in the plasmid LYS2 gene) is constructed in this work. The deletions overlap the whole coding region of the gene and provide the system for intragenic recombinational mapping of lys2 mutations in one of 14 controlled regions. A portion of these regions can be correlated with the regions on the physical map of LYS2. Mutations in two regions can be easily cloned. The system constructed gives the possibility for the study of intragenic and molecular specificity of mutagenesis. PMID- 2227396 TI - [Cloning and expression of the gene for diphtheria toxin and its subunits in Escherichia coli]. AB - The results of cloning Corynebacterium diphtheriae phi 984 tox gene and its A and B subunits in Escherichia coli are presented. Regulatory sequences of tox gene are capable to promote effective expression in E. coli cells. A set of recombinant plasmids has been obtained which can determine the synthesis of A and B individual subunits and are suitable for constructing immunotoxins by gene engineering. The diphtheria toxin of 62 kDa synthesized in E. coli has enzymatic activity and reacts with antitoxin sera. Some sites for E. coli proteases are present in tox-specific polypeptides. PMID- 2227398 TI - [Genetic analysis of spontaneous and 6-N-hydroxylaminopurine and propiolactone induced Adp+ mutants in Saccharomyces yeasts]. AB - 652 spontaneous and 6-N-hydroxylaminopurine and propiolactone-induced mutants were obtained in yeast. 598 of them were LYS2 mutants. Detailed genetic analysis of the mutants was performed, including analysis of growth pattern on lysineless medium, suppressibility by nonsense suppressors of three types and localization on the recombination map of the LYS2 gene. Mutants induced by different agents were different for all these criteria, except for distribution among the map regions. PMID- 2227399 TI - [Cytogenetic study of synapsis and crossing-over in male mice heterozygous for reciprocal translocation T(14; 15)6Ca]. AB - Synapsis and crossing over in male mice heterozygous for reciprocal translocation T (14; 15)6Ca were studied. The translocated multivalent undergoes the synaptic adjustment in the course of meiotic prophase. Translocated distal region of the 14th chromosome forms inproportionally long lateral element of synaptonemal complex. The number of chiasmata in the 14th chromosome increases from 1.02 0.02 in normal karyotype to 1.41 0.03 in heterozygous mice. The density of chiasmata in translocated, distal region is ten times higher than in the other part of the 14th chromosome. PMID- 2227400 TI - [The role of genetic and ecological factors in development of resistant phenotype in mice during experimental trichinelliasis]. AB - The role of genetic (genes for wool, eyes colour, X and Y chromosomes, H-2 haplotype) and ecological (contamination intensity leading to strengthening of illness) factors in forming phenotype of resistance in mice under experimental trichinelliasis is studied. The experiments have been performed on male and female mice CBA/Ca, BALB/c, C57/BL/6J, DBA/2J, C3HA/Mv, CC57BR/Mv, CC577W/Mv and hybrids /C57BL/6J x CBA/Ca/F having 19-25 g mass each, which were infected with trichinella larvae of Byelorussian laboratory "strains" in dosage of 5, 20, 35 and 70 units per 1 g body mass. The intensity of intestine invasion, the level of free histamine in the liver, the index of inhibition of spleen leucocyte migration on the 7th day and intensity of muscle invasion on the 30th day after contamination were defined. The analysis of the results of the study allowed to formulate the following points of regularity of trichinella resistance phenotype formation in mice: 1. The phenotype is formed as the result of interaction of genetic and ecological factors. 2. Mice of different genotypes form different phenotypes of resistance to trichinella. 3. Mice of the same genotypes form different phenotypes of resistance to intestine and muscle trichinella. The problems of inheritance and mechanisms of resistance are discussed. PMID- 2227401 TI - [Synapsis in single and double heterozygotes for partially overlapping inversions in chromosome 1 of the house mouse]. AB - Electron microscopic analysis of synaptonemal complexes (SC) in single and double heterozygotes for the partially overlapping inversions In(1)1Icg, In(1)1Rk and In(1)12Rk in the Chromosome 1 of the house mouse reveals a dependence of synapsis and synaptic adjustment on the size and location of the inversions and their interaction. In(1)1Icg contains the insertions of inverted repeats Is(HSR: 1C5)1Icg and Is(HSR: 1I)2Icg as well as inverted euchromatic region. The synaptic adjustment of the D loops by shortening of asynapsed parts of the lateral elements of SC belonging to the insertions occurs at late zygotene-early pachytene stage. After that the synaptic adjustment of the inversion loops takes place. A delay in adjustment was found in diheterozygotes In(1)1Icg/In(1)1Rk and In(1)1Icg/In(1)12Rk. Morphological alterations of the asynapted terminal segments of lateral elements preventing synaptic adjustment were found in single and double heterozygotes for In(1)1Rk and In(1)12Rk. Correspondence between the size of asynapted regions and the probability of association of XY and heteromorphic bivalents was revealed. PMID- 2227402 TI - [Hereditary polymorphism of glutathione-S-transferase in the human liver in normal conditions and in alcoholic hepatitis]. AB - A total of 100 autopsy liver extracts from Russian individuals were examined for glutathione-S-transferase I (GST1) isozymes by means of starch gel electrophoresis. The gene frequencies of GST1* 1, GST1* 2 and GST1* 0 were 0.051, 0.251 and 0.697, respectively. Analysis of data obtained and those in literature for other populations revealed the difference between European and Mongoloid groups. The GST1 0 phenotype was found in samples of liver from individuals with alcoholic hepatitis at frequency 77.3%. The gene frequencies for GST1* 1, GST1* 2 and GST1* 0 were 0.020, 0.100 and 0.879, respectively. PMID- 2227403 TI - Evolutionary implications of duplications and Balbiani rings in Drosophila. A study of Drosophila serrata. AB - Drosophila serrata, a species of subgroup montium, exhibits in its salivary-gland chromosomes a high number of inverted tandem duplications and a well-formed Balbiani ring. A photographic map, the duplications, and the Balbiani ring of this species are presented. Also presented are the most prominent puffs during normal larval development and after ecdysone treatment, as well as intercalary heterochromatin regions of the above chromosomes. These data are discussed and compared with those of Drosophila auraria, another species of subgroup montium. All the inverted tandem duplications found in both species are homozygous and are not accompanied by other types of chromosomal rearrangements. These results argue in favor of the relatively old origin of these structures. The similarity of the structure and the developmental profile of the Balbiani ring 1 in both species may indicate a necessary role served by the Balbiani ring 1 and hence its selection during evolution. PMID- 2227404 TI - Organization of the 5S rRNA genes in the soybean Glycine max (L.) Merrill and conservation of the 5S rDNA repeat structure in higher plants. AB - The 5S rRNA gene of the soybean Glycine max (L.) Merr. has been cloned on a 556 bp fragment of DNA and sequenced. This fragment contains two copies of the soybean 5S rDNA sequence, one intact and one truncated, separated by noncoding DNA. We have used this clone to investigate the organization of the 5S genes within the soybean genome and the extent of their methylation. Our results demonstrate that soybean 5S genes are clustered, organized into tandem repeats of 330 bp, and extensively methylated. Hybridization of the 5S sequence to Southern transfers of soybean DNA digested with BamHI reveals a striking ladderlike pattern. Hybridization of the soybean 5S sequence to a wide variety of plant DNAs results in similar patterns, suggesting that the 5S rDNA sequence, gene organization, and methylation pattern are conserved in many higher plants. PMID- 2227405 TI - Lack of correlation between crossing-over and chromosome distance between inversions in Drosophila ananassae. AB - Two linked inversions, AL and ZE, located in the opposite limbs of the second chromosome of Drosophila ananassae are separated from each other by nearly 32% of the total length of the second chromosome. Crossing-over between these inversions when heterozygous was studied in females and males by the salivary-gland smear technique using karyotypically homozygous stocks. The results of recombination experiments show that there is a strong suppression of recombination between inversions when heterozygous, in spite of a large euchromatic distance available for crossing-over between them. Thus there is no correlation between chromosome distance and crossing-over between heterozygous inversions in the second chromosome of D. ananassae when studied cytologically. PMID- 2227406 TI - Branched chain amino acid regulation of the ILV2 locus in Saccharomyces cerevisiae. AB - Mutant regulatory loci of the branched pathway for the biosynthesis of isoleucine valine and leucine were identified with the unusual phenotype of an amino acid dependent auxotrophy. Two mutant loci, bcs1 and bcs2, conferred branched chain amino acid sensitivity and showed independent segregation. Linkage studies defined bcs1 as a cis-acting regulatory site of ILV2 (SMR1). ILV2 upstream deletion analyses and high-copy transformation of the positive regulatory locus LEU3 ruled out the possibility of LEU3 protein binding palindromes mediating the branched chain amino acid dependent auxotrophy. In the presence of leucine and valine, the general amino acid control system (GCN4) was epistatic to bcs1 and bcs2, and under nonstarvation conditions GCN4 strains showed an increased acetolactate synthase activity over gcn4 strains. Thus in addition to general regulation of ILV2, GCN4 functions in basal level expression when the locus is subject to specific repression by pathway end product. PMID- 2227407 TI - An XXY mouse, the result of a rearrangement between one X and a Y chromosome. AB - A male mouse with irregular white spotting, typical of piebald, s, arose during an experiment designed to search for mutations induced in spermatogonial cells by ethylnitrosourea (ENU). On being examined cytologically it was found to carry 40 chromosomes but was effectively XXY since one of the two X chromosomes present was distally fused to a Y chromosome. In common with the previously described XXY mice, all of which carried 41 chromosomes, the mouse was sterile with a total absence of germ cells. Because of this, it was not possible to determine if the white spotting was inherited. The spotting could not be related to any observable abnormality of chromosomes known to carry spotting genes, nor could it be linked in any way with the X and Y fusion. It was concluded from the cytological considerations and the time interval (6 months) that had elapsed between mutagen treatment and birth of the offspring, that whereas the spotting was probably the result of ENU damage in a spermatogonial stem cell, the XY fusion was probably a later and spontaneous event. PMID- 2227408 TI - Relative growth of the skull and postcranium in giant transgenic mice. AB - Cross-sectional allometric growth patterns of the cranial and postcranial skeleton were compared between giant transgenic (MT-rGH) mice and their normal littermate controls. Body weights, external body dimensions, and a series of cranial and postcranial linear dimensions of the skeleton were determined for samples of known age. Comparative bivariate and multivariate allometric analyses were completed in order to determine whether (1) the larger transgenic mice differed significantly from the normal controls in aspects of body and skeletal proportions, and (2) any such proportion differences resulted from general allometric effects of overall weight or skeletal size increase. Results demonstrate that the transgenic mice do exhibit significantly different body and skeletal proportions than normal control adults. Allometric comparisons of the skeletal dimensions relative to body weight reveal similar coefficients of growth allometry but several differences in gamma-intercept values in the transgenic vs. control groups. The comparisons among the skeletal dimensions of the skull and postcranium generally reveal the sharing and differential extension of common growth allometries in the two groups. Thus, the elevated levels of growth hormone (GH) and insulin-like growth factor I (IGF-I) in the transgenic mice appear to result in increased overall growth for the various skeletal elements, but in the relative proportions determined by intrinsic growth controls within that system. PMID- 2227409 TI - In vivo footprint and methylation analysis by PCR-aided genomic sequencing: comparison of active and inactive X chromosomal DNA at the CpG island and promoter of human PGK-1. AB - The promoter region of the X-linked human phosphoglycerate kinase-1 (PGK-1) gene is a CpG island, similar to those often found near autosomal genes. We used ligation-mediated polymerase chain reaction (PCR) for a genomic sequencing study in which 450 bp of the human PGK-1 promoter region was analyzed for the presence of in vivo protein footprints and cytosine methylation at all CpG sites. A technique was devised to selectively visualize the DNA of the inactive X chromosome (Xi), even in the presence of the active X chromosome (Xa). We found that the human Xa in both normal male lymphocytes and hamster-human hybrids is completely unmethylated at all 120 CpG sites. In contrast, 118 of the CpG sites are methylated on the human Xi in hamster-human hybrids. The Xi in normal female lymphocytes is also highly methylated, but some GCG or CGC trinucleotides partially escape methylation; all other CpGs are fully methylated. In vivo footprinting studies with dimethylsulfate (DMS) revealed eight regions of apparent protein-DNA contacts on the Xa. Four of the footprints contained the consensus sequence of the binding site for transcription factor Sp1. The other regions include potential binding sites for transcription factors ATF, NF1, and a CCAAT-binding protein. The Xi did not show any specifically protected sequences, and with the exception of four hyperreactive sites, the in vivo DMS reactivity profile of Xi DNA was very similar to that of purified, linear Xi DNA. The implications of these findings with regard to the maintenance of methylation-free islands, X chromosome inactivation, and the chromatin structure of facultative heterochromatin are discussed. PMID- 2227410 TI - Developmentally regulated fetal thymic and extrathymic T-cell receptor gamma delta gene expression. AB - The gamma delta T-cell receptor (TCR) is the first TCR to be expressed in ontogeny in all vertebrates in which it has been examined thoroughly. Murine gamma delta cell-surface protein is detected by the fourteenth day of gestation. In this work, the activation of gamma delta RNA has been studied. Data indicate that the first TCR protein to appear in the thymus is encoded by gamma genes that are activated after cells colonize the thymus. However, the sequential appearance of different gamma delta TCR proteins during thymic ontogeny cannot be readily explained by differential temporal activation of V gamma genes in the thymus. There are distinct patterns of gamma and delta gene expression during fetal liver development and in the fetal gut (or tissue associated with it). Cells apparent in the liver of mice at birth express gamma delta cell-surface protein, but they disappear from the liver very soon afterward. One V gamma gene is rearranged and expressed prethymically. In addition, gamma gene expression is detectable in the livers of newborn athymic mice. Together, these observations indicate a thymic independent pathway of activation of TCR genes. PMID- 2227411 TI - Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of Saccharomyces cerevisiae and Schizosaccharomyces pombe. AB - The Cks1 protein is a component of the Cdc28 protein kinase in the budding yeast Saccharomyces cerevisiae. This paper reports the cloning of two homologs of the S. cerevisiae CKS1 gene from human cells. These homologs, CKShs1 and CKShs2, both encode proteins of 79 amino acids that share considerable homology at the amino acid level with the products of CKS1 from S. cerevisiae and suc1+ from the fission yeast Schizosaccharomyces pombe. Both human homologs are capable of rescuing a null mutation of the S. cerevisiae CKS1 gene when expressed from the S. cerevisiae GAL1 promoter. S. pombe suc1+ expressed from the GAL1 promoter is also capable of rescuing a S. cerevisiae cks1 null mutation. Ckshs1 or Ckshs2 protein linked to Sepharose beads can bind the Cdc28/Cdc2 protein kinase from both S. cerevisiae and human cells. The CKShs1 and CKShs2 mRNAs are expressed in different patterns through the cell cycle in HeLa cells, which may reflect specialized roles for the encoded proteins. PMID- 2227412 TI - Transcription of a yeast U6 snRNA gene requires a polymerase III promoter element in a novel position. AB - Vertebrate genes coding for U6 small nuclear RNA are transcribed by RNA polymerase III (pol III), using only upstream promoter elements rather than the A and B block internal control regions typical of most pol III transcription units. We show that expression of the U6 gene from the yeast Saccharomyces cerevisiae has two unexpected features: it requires a B block promoter element, and this element is located in a novel position, 120 bp downstream of the coding region. In tRNA genes, the B block is the primary binding site for transcription factor (TF) IIIC, whose function is to promote the subsequent binding of TFIIIB. Both factors are thus implicated in yeast U6 gene transcription. We present a model of the U6 transcription complex based on the structure of yeast and vertebrate U6 promoters. PMID- 2227413 TI - Interaction of the human immunodeficiency virus type 1 Rev protein with a structured region in env mRNA is dependent on multimer formation mediated through a basic stretch of amino acids. AB - Interaction of the human immunodeficiency virus type 1 (HIV-1) Rev protein with a structured region within env mRNA (termed RRE) mediates the export of virus structural mRNAs from the nucleus to the cytoplasm. We show that the region encompassing the basic stretch of amino acids is essential for the ability of Rev to bind to RRE RNA and function in vivo. By use of a functional truncated Rev protein in conjunction with authentic Rev, effects on gel mobilities of the Rev RRE RNA complex attributable to multimerization of Rev protein were observed. Rev proteins, unable to multimerize, failed to bind RRE RNA. Identification of Rev mutants capable of forming multimers, but unable to bind RRE RNA, suggests that the multimerization and RNA-binding domains can be distinguished and that multimerization is likely a prerequisite for formation of the RRE RNA-binding site. A mutant Rev protein, shown previously to function as a trans-dominant inhibitor of Rev function, bound to RRE RNA as a multimer to a similar extent as wild-type Rev. This observation is consistent with the hypothesis that regulation of HIV gene expression by Rev involves the interaction with cellular factors and that the trans-dominant Rev is probably defective in this function. PMID- 2227414 TI - A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation. AB - The Tat protein of human immunodeficiency virus type 1 (HIV-1) trans-activates viral gene expression and is obligatory for virus replication. Tat function is mediated through a sequence termed TAR that comprises part of the 5'-noncoding region of all HIV-1 mRNAs. This region forms a stable stem-loop structure in vitro. Recent evidence indicates that Tat binds directly to the TAR RNA sequence, and this binding is independent of the nucleotide sequence in the loop but dependent on the integrity of the upper stem. We used the electrophoretic mobility-shift assay to identify the sequence and structure specificity of this interaction and its correlation with Tat trans-activation. We show that a 3 nucleotide bulge structure (positions +23 to +25) in TAR RNA is important for both Tat interaction with TAR RNA and Tat-mediated trans-activation of gene expression. Single base substitutions at position +23 that impair Tat-mediated trans-activation in vivo also reduce binding of Tat to TAR in vitro, suggesting that the first uridine residue in the bulge is the critical base for both functions. In contrast, mutations in the loop (positions +31 to +34) and the stem (positions +9 to +12 and +49 to +52), which reduce Tat-mediated trans-activation, had no effect on Tat binding. We also show that a Tat peptide that includes the basic region required for nucleolar localization binds to TAR RNA with the same specificity as the full-length protein. We conclude that Tat binding to TAR is necessary but not sufficient by itself to account for trans-activation. PMID- 2227415 TI - Trypanosome variable surface glycoproteins: composite genes and order of expression. AB - Combinatorial processes increase the diversity of variable surface glycoproteins (VSGs) expressed by Trypanosoma equiperdum. We show here that a single telomeric pseudogene provides the 3' portion of three distinct T. equiperdum VSG genes by recombination with different 5' donor pseudogenes. Regions of sequence homology among the pseudogenes determine the sites of recombination in the formation of the expressed copies. This suggests that the recombination between any given basic copy (BC) and the expression-linked copy (ELC) depends on their sharing homology. We present evidence that this is the case and propose that such rules account for the order of expression of the VSGs. These results demonstrate how homologous recombination can generate an ordered sequence of gene expression. PMID- 2227416 TI - The b mating-type locus of Ustilago maydis contains variable and constant regions. AB - The b locus of the phytopathogenic fungus Ustilago maydis encodes a multiallelic recognition function that controls the ability of the fungus to form a dikaryon and complete the sexual stage of the life cycle. The b locus has at least 25 alleles and any combination of two different alleles, brought together by mating between haploid cells, allows the fungus to cause disease and undergo sexual development within the plant. An open reading frame of 410 amino acids has been shown to specify a polypeptide responsible for the activity of the b1 allele, and comparisons of the predicted amino acid sequences for 6 b alleles allowed identification of variable and constant regions within the coding region of the gene. Haploid strains carrying a null mutation at the b locus, created by gene disruption, are viable but fail to interact with formerly compatible strains to give an infectious dikaryon. Analysis of mutants carrying a null allele indicated that the products of different alleles of the b locus combine to form a new regulatory activity and that this activity directly or indirectly turns on the pathway leading to sexual development and pathogenesis. PMID- 2227417 TI - Identification of two polypeptide segments of CCAAT/enhancer-binding protein required for transcriptional activation of the serum albumin gene. AB - We used molecular genetic methods to generate systematically altered forms of CCAAT/enhancer-binding protein (C/EBP). The aim of our experiments was to identify regions of C/EBP that contribute to its capacity to activate transcription from the promoter of the serum albumin gene in cultured hepatoma cells. Earlier experiments had shown that the DNA-binding domain must remain intact for C/EBP to activate albumin transcription. We now provide evidence of two additional elements of C/EBP that are required for its gene-activating role. One such element occurs within a 28-residue region located close to the amino terminus of the protein. The other maps to a broader, more internal region of the protein and appears to exhibit functional redundancy. These newly defined elements of C/EBP exhibit two characteristics of "activation" domains delineated in studies of other gene regulatory proteins. First, they play no obvious role in the capacity of C/EBP to bind to its DNA substrate. Second, they retain function after being appended onto the DNA-binding domain of a different protein. Neither of these putative activating elements is characterized by overt distinction in either charge or preponderance of any particular amino acid. The more amino terminal element does, however, exhibit several features suggesting that it may assume an alpha-helical structure. These studies offer observations and reagents that will be valuable for future studies concerning the physiologic function of C/EBP. PMID- 2227418 TI - HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally. AB - Hepatocyte-specific gene expression requires the interaction of many proteins with multiple binding sites in the regulatory regions. HNF-3 is a site found to be important in the maximal hepatocyte-specific expression of several genes. We find that liver nuclear extracts contain three major binding activities for this site, which we call HNF-3A, HNF-3B, and HNF-3C. Purification from rat liver nuclear extracts of HNF-3A and HNF-3C reveals that each activity corresponds to a distinct polypeptide, as determined by SDS-PAGE. Peptide sequence derived from the most abundant species, HNF-3A, was used for synthesizing probes with which to isolate a cDNA clone of this protein. The encoded protein contains 466 amino acids (48.7 kD) and has binding properties identical to those of the purified protein. A 160-amino-acid region that does not resemble the binding domain of any known transcription factor is essential for DNA binding. The mRNA for HNF-3A is present in the rat liver but not in brain, kidney, intestine, or spleen, and the basis for this difference is cell-specific regulation of HNF-3A gene transcription. PMID- 2227419 TI - Isolation and characterization of a Ustilago maydis glyceraldehyde-3-phosphate dehydrogenase-encoding gene. AB - The complete nucleotide sequence of the glyceraldehyde-3-phosphate dehydrogenase gene from the corn smut fungus Ustilago maydis is reported. The gene encodes a 337-amino acid protein, parts of which show sequence identity to corresponding regions of GAPDH-encoding genes from other organisms. A single, putative 407-bp intron interrupts the tenth codon. Codon usage is highly biased for codons ending in cytosine. PMID- 2227420 TI - Characterization of a gene encoding a manganese peroxidase from Phanerochaete chrysosporium. AB - The complete nucleotide (nt) sequence of a gene (mnp-1) encoding manganese peroxidase isozyme 1 (MnP-1) (pI = 4.9) from Phanerochaete chrysosporium has been determined. The sequence of 2539 bp includes 526 bp of 5'-flanking sequence and 368 bp 3' to the poly(A) site. Comparison of cDNA and genomic sequences indicates six introns varying in size from 57-72 bp. Intron splice-junction sequences all adhere to the GT---AG rule. The positions of the introns show little similarity to the intron positions in the closely related lignin peroxidase-encoding genes. The 5' upstream region of the mnp-1 gene contains a TATAA element and three inverted CCAAT elements (ATTGG) at nt positions -81, -181, -195, and -304, respectively, relative to the start codon. In addition, the mnp-1 gene contains three putative heat-shock (HS) elements similar to the consensus C--GAA--TTC--G sequence, and two consensus metal response elements located within 500 bp upstream from the start codon. Furthermore, Northern-blot analysis demonstrates that mnp gene transcription is regulated by HS. PMID- 2227421 TI - Use of uracil DNA glycosylase to control carry-over contamination in polymerase chain reactions. AB - Polymerase chain reactions (PCRs) synthesize abundant amplification products. Contamination of new PCRs with trace amounts of these products, called carry-over contamination, yields false positive results. Carry-over contamination from some previous PCR can be a significant problem, due both to the abundance of PCR products, and to the ideal structure of the contaminant material for re amplification. We report that carry-over contamination can be controlled by the following two steps: (i) incorporating dUTP in all PCR products (by substituting dUPT for dTTP, or by incorporating uracil during synthesis of the oligodeoxyribonucleotide primers; and (ii) treating all subsequent fully preassembled starting reactions with uracil DNA glycosylase (UDG), followed by thermal inactivation of UDG. UDG cleaves the uracil base from the phosphodiester backbone of uracil-containing DNA, but has no effect on natural (i.e., thymine containing) DNA. The resulting apyrimidinic sites block replication by DNA polymerases, and are very labile to acid/base hydrolysis. Because UDG does not react with dUTP, and is also inactivated by heat denaturation prior to the actual PCR, carry-over contamination of PCRs can be controlled effectively if the contaminants contain uracils in place of thymines. PMID- 2227422 TI - The pAX plasmids: new gene-fusion vectors for sequencing, mutagenesis and expression of proteins in Escherichia coli. AB - A family of plasmid cloning vectors have been constructed, allowing both the sequencing and mutagenesis of foreign genes and the easy isolation of their expression products via fusion proteins in Escherichia coli. Fusion proteins can be inducibly expressed and isolated by affinity chromatography on APTG-Sepharose. The fusion protein consists of beta-galactosidase at the N-terminus, linked by a collagen 'hinge' region containing blood coagulation factor Xa cleavage site to the foreign protein at the C terminus. The factor Xa cleavage site at the N terminal side of the foreign protein allows the release of the desired amino acid sequence under mild conditions. A multiple cloning site in all three reading frames and stop codons followed by the strong lambda t0 terminator facilitate simple gene insertions and manipulations. The intergenic region of the phage f1 inserted in both orientations allows the isolation of single-stranded DNA from either plasmid-strand for sequencing and mutagenesis. This vector family has been successfully used for the expression and purification of the isoleucyl-tRNA synthetase from Saccharomyces cerevisiae and the histidyl-tRNA synthetase from E. coli. PMID- 2227423 TI - Construction of mobilizable vectors derived from plasmids RP4, pUC18 and pUC19. AB - Mobilizable narrow-host-range plasmids were constructed from pUC18 and pUC19 by addition of a segment of pSUP2021 bearing the basis of mobilization (bom) site and origin of transfer (oriT) of RP4. One pair of expression vectors, pARO180 and pARO190, retains the beta-lactamase (bla) gene and twelve of the 13 restriction enzyme multiple cloning sites (MCS) of pUC18/19. Another pair was created by replacing the bla gene with the gene encoding kanamycin resistance (kan) from Tn5. The molecules replicate to high copy number in Escherichia coli and Enterobacter aerogenes. They can be transferred efficiently to other Gram- bacteria from the mobilizing strain, E. coli S17-1. In non-enteric strains, the new plasmids can be used as suicide vectors in site-specific insertional mutagenesis. PMID- 2227424 TI - Construction of cloning vectors using the Vibrio harveyi luminescence genes luxA and luxB as markers. AB - A synthetic oligodeoxyribonucleotide harboring four new restriction sites was inserted into the luxB gene of Vibrio harveyi. This insertion did not disrupt the reading frame. An active beta-subunit was synthesized since a plasmid with both the luxA and mutated luxB genes conferred upon Escherichia coli the bacterial luciferase (Lux) phenotype in the presence of an aldehyde. Ligation of a piece of foreign DNA at these new cloning sites in the vector extinguish the Lux phenotype of the transformed bacteria. Therefore, the plasmid was used as a cloning vector, and recombinant DNA-containing bacteria were detected by the loss of bioluminescence. To create more versatile plasmids, the intergenic region of phage f1 was inserted outside of the lux genes. The selection by loss of bioluminescence presents several advantages over the white/blue selection of the lacZ gene on indicator plates. PMID- 2227425 TI - Nucleotide sequence of mkaD, a virulence-associated gene of Salmonella typhimurium containing variable and constant regions. AB - We have identified the nucleotide (nt) sequence of mkaD, a virulence-associated gene of the Salmonella typhimurium virulence plasmid, pEX102. The gene shows 98% homology on nt sequence level to mkfA, a corresponding gene of the S. typhimurium virulence plasmid pIP1350. The few nt changes, however, caused more extensive changes on the amino-acid level. The differences between mkaD and mkfA were clustered in distinct variable regions rather than being randomly scattered along the sequence. A third salmonellar virulence plasmid, pLT2, contained an mkaD gene identical to that of pEX102. Our observation suggests that the conserved virulence determinant on the plasmids of Salmonellae may contain different alleles of the same gene. PMID- 2227426 TI - Multiple endo-beta-1,4-glucanase-encoding genes from Bacillus lautus PL236 and characterization of the celB gene. AB - A Bacillus lautus strain was isolated from compost by its ability to degrade microcrystalline Avicel cellulose and acid-swollen cellulose. Three DNA fragments cloned in Escherichia coli encoded at least four endo-beta-1,4-glucanases (EG), of which at least two were contained on one DNA fragment. Another fragment, of 2.5 kb and carrying celB, was cloned in the shuttle-vector plasmid, pJKK3-1, and expressed in E. coli and Bacillus subtilis. The fragment was sequenced and shown to encode a 62-kDa protein, which was found as a 56-kDa mature and active EG in extracts of E. coli and in the supernatant of B. subtilis. The deduced amino acid (aa) sequence has a homology of 37% identical aa on a stretch of 295 aa to EG-E of Clostridium thermocellum. A low level of homology is detected with the Bacillus-type EG. PMID- 2227428 TI - Resistance to pactamycin in clones of Streptomyces lividans containing DNA from pactamycin-producing Streptomyces pactum. AB - A pactamycin (Pc)-resistance determinant (pct) from Streptomyces pactum has been isolated on a 4.9-kb KpnI fragment. The original construct involving plasmid pIJ702 was highly unstable in Streptomyces lividans, leading to deletion of the pct gene from the vector. Subcloning of pct into an alternative vector (pOJ160) led to the generation of a more stable clone which possessed Pc-resistant ribosomes, and reconstitution analysis established that 16S rRNA was responsible for such resistance. Post-transcriptional modification of rRNA is probably the mechanism of resistance since the cloned DNA fragment did not appear to encode 16S rRNA. PMID- 2227427 TI - Development of a cloning system in Mycoplasma pulmonis. AB - A system suitable for recombinant DNA manipulation in mycoplasmas was developed using the cloned antibiotic-resistance genes of Tn4001 and Tn916. An integrative plasmid containing one of the resistance markers was inserted into the genome of Mycoplasma pulmonis to form a recipient strain. This was accomplished by transformation and homologous recombination between chromosomal DNA sequences cloned onto the integrative plasmid. A second vector, the cloning vector, containing the same plasmid replicon and alternate resistance marker, carried cloned foreign DNA. When transformed into mycoplasmal recipients, homologous recombination between plasmid sequences resulted in integration of the cloning vector and foreign DNA. A Brucella abortus gene coding for a 31-kDa protein and the P1 structural gene and operon from Mycoplasma pneumoniae were introduced to examine the feasibility of developing mycoplasma as cloning hosts. Recombinant plasmids as large as 20 kb were inserted into M. pulmonis, and the integrated foreign DNA was stably maintained. The maximum size of clonable DNA was not determined, but plasmids larger than 22 kb have not been transformed into mycoplasmas using polyethylene glycol. Also the size of genome (800-1200 kb) may affect the stability of larger inserts of foreign DNA. This system is applicable to any mycoplasma capable of transformation, homologous recombination and expression of these resistance markers. Because of their lack of a cell wall, mycoplasmas may be useful cloning hosts for membrane or excreted protein genes from other sources. PMID- 2227429 TI - Cloning and expression of two genes encoding highly homologous hemolysins from a Kanagawa phenomenon-positive Vibrio parahaemolyticus T4750 strain. AB - We have cloned and sequenced the gene encoding thermostable direct hemolysin (TDH), a possible virulence factor in Vibrio parahaemolyticus gastroenteritis, from a Kanagawa-phenomenon-positive strain, T4750. This strain was found to contain two sequences (tdhA and tdhS) homologous to the tdh gene previously reported by Nishibuchi and Kaper [J. Bacteriol 162 (1985) 558-564] and Taniguchi et al. [Microb. Pathog. 1 (1986) 425-432]. Sequence homology of the coding regior between tdhA and tdhS was 97.2%. The deduced amino acid (aa) sequence of TdhA, excluding the putative signal peptide was identical to that of TDH protein purified from V. parahaemolyticus [Tsunasawa et al., J. Biochem. 101 (1987) 111 121] except for Glu118 instead of Gln118. Although the aa sequence deduced from the second gene, tdhS, differed in eight residues from the TDH protein, it agreed with the sequence of Tdh deduced from the previously cloned tdh gene. Both tdhA and tdhS expressed biologically active hemolysins in Escherichia coli. While the apparent molecular size of TDH purified from a culture supernatant of V. parahaemolyticus T4750 was identical to TdhA protein synthesized in E. coli, it was larger than TdhS. Only one band was detected in the culture supernatant of V. parahaemolyticus T4750 by Western blotting; its mobility was indistinguishable from that of purified TDH. These data suggest that tdhA is the structural gene for TDH found in the culture supernatant of V. parahaemolyticus T4750, and that there was only partial, if any, tdhS expression in the strain T4750 under the test conditions employed. PMID- 2227430 TI - Cloning and expression in a heterologous host of the complete set of genes for biosynthesis of the Streptomyces coelicolor antibiotic undecylprodigiosin. AB - A fragment of DNA carrying the hitherto unisolated members of the cluster of genes (red) for biosynthesis of the red-pigmented antibiotic undecylprodigiosin of Streptomyces coelicolor A3(2) was isolated. This was done by cloning random fragments of S. coelicolor DNA into the closely related Streptomyces lividans 66 and recovering a clone that caused overproduction of undecylprodigiosin. The effect was probably due to the presence of the cloned redD gene, which functions as a positive regulator of the expression of the red cluster, activating the normally poorly expressed red genes of S. lividans. Two fragments from either end of the red cluster were cloned adjacent to each other on a low-copy-number Streptomyces vector. Double crossing-over occurring between these plasmid-borne sequences and the chromosomal copy of the same DNA in S. coelicolor led to isolation of the entire red cluster as a single cloned fragment. Isolation of antibiotic biosynthetic genes by the effects of an activator in a self-cloning experiment, and in vivo reconstitution of a large cluster of genes by homologous recombination, may turn out to be usefully generalizable procedures. PMID- 2227431 TI - Organization and transcription of Volvox histone-encoding genes: similarities between algal and animal genes. AB - The nucleotide sequences of two non-allelic histone H2A-H2B gene loci of the green alga Volvox carteri have been determined. Each locus contains a divergently arranged H2A-H2B gene pair. The encoded proteins differ in one (H2A) and 16 positions (H2B), respectively. The coding regions are separated by short intercistronic segments (256 bp and 298 bp) containing TATA boxes and a central tandem repeat of a conserved 20-bp element as the putative histone-specific transcription signals. The 3'-untranslated regions exhibit a characteristic 3' palindrome and weakly conserved spacer elements. Transcription in one gene locus was shown to initiate 48 bp upstream from H2A and 59 bp upstream from H2B. Contrary to higher plants, V. carteri histone mRNAs are nonpolyadenylated. S1 mapping and Northern-blotting experiments indicated that V. carteri histone mRNAs are terminated at the 3'-palindrome by the same mechanism that operates in vertebrates and sea urchins. PMID- 2227432 TI - Two evolutionarily divergent genes encode a cytoplasmic ribosomal protein of Arabidopsis thaliana. AB - Two clones of Arabidopsis thaliana possessing high sequence identity to the yeast gene encoding ribosomal (r) protein L3 were isolated by heterologous DNA hybridization. The coding regions of these two clones have approx. 63% amino acid (aa) sequence identity to the yeast L3 r-protein and 85% aa sequence identity to each other. Both genes are expressed in shoots. The presence of two divergent genes in A. thaliana raises the possibility that the gene products participate in the formation of functionally distinct ribosomes. PMID- 2227433 TI - Biologically active A-chain of the plant toxin ricin expressed from a synthetic gene in Escherichia coli. AB - To assess the biological activity and pharmacokinetic properties of nonglycosylated ricin A-chain (RA), we have obtained the polypeptide following expression of a synthetic 842-bp RA gene in Escherichia coli. Expression of the gene was carried out using the phage T5 PN25 promoter fused to the E. coli lac operator. The RA polypeptide was synthesized in a completely soluble form and was purified in one step by immunoabsorption. It was shown to be as cytotoxic for a human cell line as both native RA and chemically deglycosylated native RA. Reconstituted whole ricin and an immunotoxin containing the recombinant RA were also biologically active. Immunotoxins made with recombinant and deglycosylated RA had similar clearance rates in vivo showing, after a short period of rapid elimination, stabilities far higher than that of an immunotoxin made with native RA. Our results show that the complete elimination of sugar side chains from the RA is not sufficient to entirely eradicate the rapid initial in vivo clearance of RA-based biologicals. PMID- 2227434 TI - Two highly reiterated nucleotide sequences in the low C-value genome of Panagrellus redivivus. AB - Two families of highly reiterated satellite nucleotide (nt) sequences have been found in the genome of the sexually separated nematode Panagrellus redivivus. The repeats are arranged in tandem arrays but the different satellites are not intermingled. Monomeric lengths are of 155 bp for one kind and 167 bp for the other; they were named E155 and E167. The A + T content is elevated in both families (i.e., 59.5%, and 65.3%, respectively). No similarity was found between the two satellites nor to other known highly repetitive elements. Furthermore, nt methylation as well as transcriptional activity were negative. An internal subrepeating unit, about 30 bp long, was observed in E167, implying that it could have evolved from a shorter sequence. Reiteration frequencies are approx. 30,000 and 40,000 copies per haploid genome, for E155 and E167, respectively, constituting together about 17% of the total DNA. This figure is astonishingly high, considering a C-value of 70,000 kb in P. redivivus, which is thought to be the lower limit for metazoans. Hence, the genome complexity is approx. 58,000 kb. In contrast to the nematodes Ascaris lumbricoides and Parascaris equorum, however, P. redivivus does not seem to eliminate large blocks of satellite DNA in the presomatic cells during early development. PMID- 2227435 TI - Isolation and characterization of the gene encoding bovine adenylate kinase isozyme 2. AB - Mitochondrial adenylate kinase isozyme 2 (AK2) exists in two isoforms, AK2A and AK2B, which have the same amino-acid sequence except for the C-terminal portion. We have isolated the gene encoding AK2 from a bovine genomic library. The gene covers about 25 kb and consists of seven exons and six introns. The nucleotide sequences from exon 1 to the 5' half of exon 6 encode the portion common to AK2A and AK2B, while the sequences of the 3' half of exon 6 and exon 7 direct the unique portions of AK2A and AK2B, respectively. Therefore, an alternative splicing mechanism is suggested in generating two types of mRNA encoding AK2A and AK2B. The 5'-flanking region of the gene lacks a TATA box, but contains three CAAT boxes. The G + C content of this region is high and eight copies of GC box are found. These features of the promoter region resemble those of 'housekeeping' genes. S1 mapping and primer extension analyses revealed multiple transcription start points. The 581-bp region just upstream from the start codon functions as a promoter in the expression of the cat gene in Chinese hamster ovary cells. PMID- 2227436 TI - A novel expression vector for high-level synthesis and secretion of foreign proteins in Escherichia coli: overproduction of bovine pancreatic phospholipase A2. AB - A novel expression plasmid (pTO-N) has been constructed that allows for the production of large quantities of foreign proteins (or fragments thereof) in an unfused state. The vector has a strong and tightly regulated T7 gene 10 promoter and the ompA Shine-Dalgarno (SD) sequence, followed by the ompA sequence and a cloning linker region. The mRNAs produced by the vector are protected by secondary structures at both ends of the mRNAs. The OmpA signal peptide directed the synthesized proteins into the periplasmic space of Escherichia coli. Phospholipase A2 and prophospholipase A2 from bovine pancreas have been produced to a high level by using this expression vector. One additional feature, which is essential for the stable maintenance of the plasmid in the E. coli expression host, BL21 (DE3)[pLysS], is the shortened distance between the 5' secondary structure sequence (immediately following the gene 10 promoter) and the SD sequence. This vector could be particularly useful for synthesis of toxins in E. coli. PMID- 2227437 TI - Molecular cloning and characterization of rat liver catechol-O-methyltransferase. AB - The coding sequence of rat liver catechol-O-methyl-transferase (COMT; EC 2.1.1.6) was determined from rat cDNA and genomic libraries were screened with DNA probes and specific antiserum. The open reading frame consisted of 663 nucleotides coding for a 221-amino acid (aa) polypeptide with a deduced Mr of 24,747. No obvious hydrophobic signal sequence, membrane-spanning domains, or potential N glycosylation sites were found in this sequence. The identity of the clone and the accuracy of the sequence was verified by direct aa sequencing of the tryptic peptides derived from the purified rat liver enzyme. Primer extension analysis showed that the transcription start point of the rat liver COMT mRNA was 450 bp upstream from the translation start codon. A putative polyadenylation signal (ATTAAA) was found in the 3'-noncoding region. The predicted size of the COMT transcript was 1.8-2.0 kb, which could be confirmed from Northern hybridization analyses of the isolated rat liver mRNA. One polypeptide of 25 kDa, could be immunoprecipitated with anti-COMT antibody from in vitro translation of rat liver mRNA. Employing the DNA blot analysis only one COMT-encoding gene was found in the rat genome. PMID- 2227438 TI - Cloning and functional analysis of the rat ornithine decarboxylase-encoding gene. AB - We have isolated a functional gene (ODC) encoding rat ornithine decarboxylase (ODC; EC 4.1.1.17) from a partial rat liver genomic DNA bank. The entire gene is located on a 7776-bp BamHI fragment and was shown to comprise twelve exons, of which ten encode the ODC protein (exons III-XII). Introduction of the BamHI fragment into an ODC-deficient hamster cell line restores ODC activity, indicating that the gene is functional. Comparison of the structure and nucleotide (nt) sequence of the rat ODC gene with recently reported mouse ODC genes, reveals that the gene is highly conserved. Primer extension analysis and RNA sequencing demonstrates that the transcription start point of rat ODC mRNA is located 303 nt upstream from the A residue in the start codon. Compared with our previously published sequence of the rat ODC cDNA, this indicates that a short sequence at the extreme 5' end of our cDNA clone represents a cloning artefact. The correct 5' leader of ODC mRNA, which is very G + C rich (62%), can be folded into a highly stable secondary structure, which may play a role in the translational control of ODC activity. Like in mouse, the promoter region of rat ODC is also extremely rich in G + C, and contains a TATA box and several putative SP1-binding sites. Possible binding sites for other transcription factors, like AP-1, AP-2 and CREB, can also be observed in the promoter region and, moreover, in the first intron.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227440 TI - Rapid two-stage polymerase chain reaction amplification of chromosomal DNA segments in lysates made from monolayer cultures attached to microcarrier beads. AB - We describe a method for the rapid two-stage amplification and detection by ethidium bromide staining of chromosomal nucleotide (nt) sequences in lysates made directly from anchorage-dependent cells attached to microcarrier beads. The procedure circumvents the need for cell detachment steps prior to analysis, facilitates the collection, transfer, and manipulation of the cells being studied, and makes unnecessary the use of Southern-blot hybridization for identification of specific nt sequences present in a small fraction of cells within a heterogeneous population. PMID- 2227439 TI - Human ornithine decarboxylase-encoding loci: nucleotide sequence of the expressed gene and characterization of a pseudogene. AB - Previous studies have shown that human ornithine decarboxylase (ODC)-encoding sequences map to two chromosome regions: 2pter-p23 and 7cen-qter. In the present work we have cloned the expressed human ODC gene from a genomic library of myeloma cells that overproduce ODC protein due to selective gene amplification and determined its entire nucleotide sequence. The gene comprises 12 exons and 11 introns and spans about 8 kb of chromosome 2 DNA. The organization of the human gene is very similar to that of the mouse and rat, with the major difference being the presence of longer intronic sequences in the human gene. Some of these differences can be accounted for by the insertion of four Alu sequences in the human gene. Several potential regulatory elements are present in the promoter region and in 5'-proximal introns, including a TATA box; GC boses; AP-1-, AP-2- and NF-1-binding sites; and a cAMP-responsive element. The 5'-untranslated sequence of ODC mRNA is extremely GC-rich, and computer predictions suggest a very stable secondary structure for this region, with an overall free energy of formation of -225.4 kcal/mol. In addition to the active ODC gene on chromosome 2, ODC gene-related sequences were isolated from human chromosome 7-specific libraries and shown to represent a processed ODC pseudogene. PMID- 2227442 TI - Evolutionary conservation of target sequences for cis-acting regulation in c-myc exon 1 and its upstream region. AB - Transcriptional control of the c-myc proto-oncogene, an important factor in cellular growth, differentiation and in the genesis of various neoplasms, is mediated by multiple positive and negative regulators in the 5' end region of the gene. Here, we report the nucleotide sequence of the first c-myc exon and its upstream region from woodchuck, a rodent which can develop liver tumors associated with c-myc activation [Moroy et al., Nature 324 (1986) 276-279]. Alignment of these sequences with the corresponding human and murine regions shows a surprisingly high homology between woodchuck and human, and suggests the absence of species-specificity in the fundamental regulatory elements which govern c-myc expression. PMID- 2227441 TI - The primary structure of rat ribosomal protein L9. AB - The amino acid (aa) sequence of rat ribosomal (r) protein L9 was deduced from the nucleotide (nt) sequence in a recombinant cDNA and confirmed from the N-terminal aa sequence of the protein. L9 contains 192 aa and has an Mr of 21879. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 20-23 copies of the L9 gene. The mRNA for the protein is about 800 nt in length. Rat L9 is related to Saccharomyces cerevisiae YL11, Methanococcus vannielii L6, Escherichia coli L6 and other members of the prokaryotic L6 family. The protein contains a possible internal duplication of 11 aa. PMID- 2227443 TI - Characterization and nucleotide sequence of the gene encoding the human pyruvate dehydrogenase alpha-subunit. AB - Genomic clones encompassing the entire gene (PDH alpha) encoding the human pyruvate dehydrogenase alpha-subunit (PDH alpha) have been isolated by screening a leukocyte genomic library in the cloning vector, lambda EMBL4. The PDH alpha gene spans 17082 bp and is composed of eleven exons and ten introns. All intron/exon splice junctions follow the GT/AG rule. A total of seven Alu repeats were found in five introns. The entire nucleotide (nt) sequence of the PDH alpha gene has been determined and typical consensus promoter sequences in the 5' flanking region were found. The results of primer extension analysis imply that the PDH alpha gene transcription start point (tsp) is a thymine residue 124 bp upstream from the ATG start codon in exon 1. The structural organization and the tsp were compared with the recent report [Maragos et al., J. Biol. Chem. 264 (1989) 12294-12298]. Analysis of the PDH alpha gene resolves existing discrepancies among four published sequences of PDH alpha cDNAs. A 93-bp sequence that was missing in our sequence of cultured foreskin fibroblast PDH alpha cDNA [Koike et al., Proc. Natl. Acad. Sci. USA 85 (1988) 41-45] was identified in the gene as exon 6. PMID- 2227444 TI - The proximal 5'-flanking region of the gene encoding human growth hormone releasing factor contains an inserted Alu sequence. PMID- 2227445 TI - A totally synthetic plasmid for general cloning, gene expression and mutagenesis in Escherichia coli. AB - A first totally synthetic Escherichia coli plasmid has been designed, constructed and shown to be a functional, stable, high-copy cloning vector. The FokI method of gene synthesis [Mandecki and Bolling, Gene 68 (1988) 101-107] was used to assemble the plasmid from 30 oligodeoxyribonucleotides. The plasmid contains synthetic modules for the beta-lactamase-encoding gene (bla), replication origin, lacZ gene fragment and multicloning site. The plasmid is patterned after the pUC type plasmids and has a copy number similar to that of pUC plasmids. The major changes introduced include the removal of nearly 50% of the restriction sites present in pUC plasmids, reduction of plasmid size to 2050 bp, and introduction of transcription terminators downstream from both the bla gene and lacZ fragment. The changes facilitate a number of techniques, such as cloning, mutagenesis, expression and restriction analysis. PMID- 2227446 TI - Sequence comparison of mecA genes isolated from methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. PMID- 2227447 TI - The structure of the trpE, trpD and 5' trpC genes of Bacillus pumilus. PMID- 2227448 TI - Nucleotide sequences of genes encoding heat-stable and heat-labile glyceraldehyde 3-phosphate dehydrogenases; amino acid sequence and protein thermostability. PMID- 2227449 TI - Chloramphenicol resistance in Campylobacter coli: nucleotide sequence, expression, and cloning vector construction. AB - A chloramphenicol-resistance determinant (CmR), originally cloned from Campylobacter coli plasmid pNR9589 in Japan, was isolated and the nucleotide sequence determined, which contained an open reading frame of 621 bp. The gene product was identified as Cm acetyltransferase (CAT), which had a putative amino acid sequence that showed 43% to 57% identity with other CAT proteins of both Gram+ and Gram- origin. Although expression of the cat gene was constitutive in both C. coli and Escherichia coli, results of primer extension experiments indicated that transcription was initiated at different sites in these two species. A kanamycin-resistance determinant, identified as the aphA-3 gene, was located downstream from the cat gene. The codon usage of the cat gene is very different from that used in E. coli, however, the CAT polypeptide was synthesized in large amounts in E. coli maxicells. Therefore, the codon usage bias is not one of the obstacles which affects Campylobacter spp. gene expression in E. coli. New Campylobacter cloning vectors were constructed in this study. PMID- 2227450 TI - Cloning and characterization of the asd gene of Salmonella typhimurium: use in stable maintenance of recombinant plasmids in Salmonella vaccine strains. AB - The asd mutants of Salmonella typhimurium have an obligate requirement for diaminopimelic acid (DAP) and will undergo lysis in environments deprived of DAP. This has allowed the development of a balanced-lethal system for the expression of heterologous antigens in vaccine strains using vectors containing the wild type asd gene from Streptococcus mutans and asd mutant Salmonella hosts [Nakayama et al., Biotechnology 6 (1988) 693-697]. We have cloned the asd gene from S. typhimurium, characterized the gene product and used this gene to construct Asd+ expression cloning vectors. In addition we have constructed an asd cassette and a transposon derived from Tn5 that allow the rapid modification of other vectors for use with delta asd vaccine strains of S. typhimurium adding versatility to the Asd+ vector/delta asd host system of plasmid maintenance. PMID- 2227451 TI - Cloning, expression and characterization of the Sau3AI restriction and modification genes in Staphylococcus carnosus TM300. AB - The genes encoding the restriction enzyme (ENase) and modification enzyme (MTase) of Staphylococcus aureus 3A (recognition sequence 5'-GATC-3') have been cloned in Staphylococcus carnosus TM300 using the vector pCA44. Clones carrying both genes were isolated from DNA libraries prepared with MboI + BamHI. The DNA region encoding M.Sau3AI was subcloned on a 3.66-kb EcoRV fragment in vector pT181mcs. Plasmids purified from the clones were resistant to digestion with Sau3AI, indicating that the sau3AIM gene was expressed and the product was functional in S. carnosus. Cell lysates of clones with both activities encoded on plasmid pSEM7, cut DNA with the same pattern as Sau3AI, showing that the sau3AIR gene was also expressed and the ENase was functional in S. carnosus. Sequence analysis shows that both genes are transcribed in the same direction and encode polypeptides with calculated Mrs of 56,477 for R.Sau3AI and 47,300 for M.Sau3AI. Efforts to clone one or both genes in Escherichia coli have so far failed. PMID- 2227452 TI - Construction of a series of pSAM2-based integrative vectors for use in actinomycetes. AB - We have developed vectors which allowed integration of cloned DNA at a single site in the chromosome of Streptomyces lividans 66. These vectors made use of (1) an Escherichia coli replicon, (2) a thiostrepton (Th)- and a streptomycin/spectinomycin-resistance gene for selection in Streptomyces, (3) a 3.5-kb fragment of the Streptomyces integrative plasmid pSAM2 containing its xis and int genes as well as its attachment site, attP, to direct the integration of the vectors at the chromosomal pSAM2 attachment site attB, (4) the origin of transfer of the IncP broad-host-range plasmid RK2 which allowed the mobilization of the vectors from E. coli to S. lividans, and (5) the Th-inducible tipA promoter to permit regulated transcription of cloned genes. We demonstrated that pPM927, a plasmid which contained all of these elements, was able to transfer cloned fragments from E. coli to S. lividans by conjugation, stably integrate into the chromosome, and express cloned genes from the tipA promoter. Furthermore, since pPM927 contained the pBR322 replicon, cloned fragments could be conveniently recovered from the S. lividans chromosome for analysis in E. coli by cleavage of genomic DNA isolated from transformed strains, intramolecular ligation and transformation. Since we have shown that the pSAM2 attB site forms part of a conserved prokaryotic tRNA gene, these integrative vectors are potentially useful tools for analysis and expression of genes in diverse bacteria. PMID- 2227453 TI - Cloning, expression and sequence analysis of an endolysin-encoding gene of Lactobacillus bulgaricus bacteriophage mv1. AB - The lysA gene specifying an endolysin of Lactobacillus delbrueckii subsp. bulgaricus bacteriophage mv1, was cloned and expressed in Escherichia coli. The 4.05-kb restriction fragment containing this gene was analysed by restriction and deletion mapping, and by subcloning. The nucleotide sequence of a 1150-bp fragment coding for an active lysin was determined. The lysA gene consists of 585 bp and codes for a protein of a deduced Mr of 21,120, which agrees with the size based on in vivo transcription/translation studies. The deduced amino acid sequence of the mv1 lysin (LysA) was compared to that of other known lytic enzymes. Significant homology was observed with the N-terminal portion of the muramidase of the fungus Chalaropsis and that of the muramidase of the Streptococcus pneumoniae phage Cp-1, suggesting that LysA might be a muramidase. In E. coli, the cloned lysA gene was able to complement the muramidase-defective bacteriophage lambda Ram5, proving that the products of these two genes are interchangeable. The lysA gene is preceded by an open reading frame with unknown function and no characteristic prokaryotic promoter sequences could be detected upstream from lysA, suggesting that this gene is part of an operon. PMID- 2227454 TI - Cloning, sequence and expression in Escherichia coli of the Methylobacillus flagellatum recA gene. AB - By means of interspecific complementation of an Escherichia coli recA- mutation with phasmids containing a gene bank from an obligate methylotroph, Methylobacillus flagellatum (Mf), the recA+ gene from this bacterium was identified. When expressed in an E. coli recA- host, it can function in recombination, DNA repair, and prophage induction. The nucleotide sequence of the gene has been determined. The coding region consists of 1032 bp specifying 344 amino acids. The deduced RecA protein structure shows a striking homology with RecA from other bacteria, except for the C-terminal region and some residues which were proposed to be responsible for the coprotease ability of RecA proteins. The region preceding the recA-Mf gene start codon has no SOS box--the LexA repressor binding site. Expression of the recA-Mf gene in E. coli proved to be DNA-damage independent. PMID- 2227455 TI - Molecular analysis of the Bacteroides fragilis recA gene. AB - The nucleotide sequence of a 2.5-kb DNA segment containing the Bacteroides fragilis recA gene was determined. The coding region of the recA gene specifies a protein of 318 amino acids. The RecA protein of B. fragilis shows significant homology with that of Escherichia coli, Thiobacillus ferrooxidans, Pseudomonas aeruginosa and Proteus mirabilis. No SOS box characteristic of LexA-regulated promoters could be identified in the 5'-noncoding region of the B. fragilis recA gene. Promoter activity of the cloned recA gene in E. coli was located within a 113-bp fragment of the B. fragilis DNA by in vitro construction of operon fusions with a promoterless lacZ gene. The transcription start point for this gene in B. fragilis was determined by primer extension analysis. PMID- 2227456 TI - Cloning, sequencing, and transcriptional analysis of the recA gene of Pseudomonas cepacia. AB - A recombinant plasmid carrying the recA gene of Pseudomonas cepacia complements a recA mutation of Escherichia coli and restores UV and methylmethane sulfonate resistance, as well as recombinational proficiency. The predicted amino acid (aa) sequence of P. cepacia RecA (347 aa; Mr, 37256) is highly homologous to the RecA proteins from Thiobacillus ferrooxidans (74% aa homology), Pseudomonas aeruginosa (72%), E. coli (71%), Anabaena variabilis (61%), and Synechococcus sp. strains PCC7002 (59%). The transcription of the recA gene in P. cepacia and E. coli, which starts at almost the same site, was enhanced slightly by UV irradiation in the former and markedly in the latter bacteria. An SOS box characteristic to LexA regulated promoters, along with the -10 and -35 consensus sequences, was found in the 5' upstream region of the P. cepacia recA gene. PMID- 2227458 TI - Never too old to teach. PMID- 2227457 TI - Cloning and sequencing of the locus encoding the large and small subunit genes of the periplasmic [NiFe]hydrogenase from Desulfovibrio fructosovorans. AB - The genetic locus encoding the periplasmic [NiFe]hydrogenase (Hyd) from Desulfovibrio fructosovorans was cloned and sequenced. The genes of this two subunit enzyme have an operon organization in which the 0.94-kb gene encoding the small subunit precedes the 1.69-kb gene encoding the large subunit. A Shine Dalgarno sequence is centered at -9 bp from the ATG of both subunits. The possible presence of another open reading frame downstream from the large-subunit encoding gene is considered. The N-terminal sequence of the large 61-kDa subunit deduced from the nucleotide sequence is in perfect agreement with the results of the amino acid (aa) sequence determined by Edman degradation. A 50-aa leader peptide precedes the small 28-kDa subunit. The aa sequence of the enzyme shows nearly 65% homology with the [NiFe]Hyd aa sequence of Desulfovibrio gigas. Comparisons with a large range of Hyds from various bacterial species indicate the presence of highly conserved Cys residues, the implications of which are discussed from the point of view of nickel atom and cluster accommodation. PMID- 2227459 TI - Atrial fibrillation in the elderly: management update. AB - Non-valvular atrial fibrillation is associated with a markedly increased risk of embolic stroke in elderly persons. Evidence is accumulating that anticoagulation with warfarin or aspirin may be effective in reducing this risk. PMID- 2227460 TI - Soft tissue rheumatism of the upper extremities: diagnosis and management. AB - Upper extremity tendinitis and bursitis are usually the result of repetitive microtrauma, probably resulting in disruption of fibers. A focus of inflammation often occurs, producing pain, spasm, and disability. With a careful history and physical exam, the diagnosis can be made, distinguishing soft tissue rheumatism from arthritis. Treatment consists of rest, heat or ice, and frequently, the use of non-steroidal anti-inflammatory drugs or injections to control the inflammatory response. Protection from repeated trauma may be beneficial in preventing recurrence. PMID- 2227461 TI - Practical nutritional advice for the elderly, Part II: Modification and motivation. A Geriatrics panel discussion. PMID- 2227462 TI - Infection control in the nursing home: the physician's role. AB - Infection control in the nursing home or long-term care facility is an increasingly complex activity. The high rates (approximately 15%) and special risks (group activities, crowding) for nosocomial infection demand special attention by attending physicians. Some specific responsibilities include: recognition of infection; knowledge and use of basic infection control principles; appropriate antibiotic use; review of immunizations; facilitation of communications among office, hospital, and long-term care facility; and involvement with infection control program(s). PMID- 2227463 TI - E. D. Vaughan, Jr., MD: newer options in managing prostate disease. Interview by Richard L Peck. PMID- 2227465 TI - Variations in the life span, enzymes and lipid peroxide levels in ageing Caryedon serratus (Coleoptera: Bruchidae). AB - In the bruchid Caryedon serratus, life span of males was longer than that of females. Catalase showed an increasing trend with age in both the sexes but the increase was higher in males. However, an opposite trend was observed for lipid peroxide levels. A rapid decline of NADH and succinate dehydrogenases in females is indicative of early depletion of food reserves due to the higher metabolic rate. Thus, in C. serratus, the factors contributing to relatively higher life span of males are efficient homeostatic defence mechanisms and low oxidative damage in males, early maturity and more reproductive demands in females. PMID- 2227464 TI - Geriatric autopsies: it's time to get involved. AB - As calls for physician accountability mount up, physicians who request autopsies may be deemed more professional. This will be particularly true if they understand the terminology. PMID- 2227466 TI - On the strategy of directed assembly and its relevance to ageing. AB - The strategy which Nature has chosen to generate complex, asymmetric structures has been to build on previously established structures and to render the internal chemistry asymmetric by a close association with asymmetrically distributed, stable topological organizers. This is what we call the strategy of directed assembly. Ageing and the strategy of directed assembly seem to be general for biological systems displaying history-dependent development. We believe that it is this strategy which imposes severe limitations on topological organizer turnover rates and, therefore plays a major role in initiating the ageing process. PMID- 2227467 TI - Labyrinth learning impairment in patients with early symptoms of presenile dementia. AB - 21 patients (54 +/- 7 years old) with early cognitive deficit (ECD) during the presenile stage of presumptive primary degenerative dementia (mild stage) and 14 patients (54 +/- 4 years old) with early cognitive deficit with a background of cardiovascular disease (CVD) were examined in a labyrinth learning test of Milner (modified by Roth). 15 patients in the ECD group made 3 times more errors to negative fields (p less than 0.01), about 10 times more errors to positive fields (p less than 0.01) and needed treble the amount of time for passing through the labyrinth (p less than 0.01) compared with a healthy control group (51 +/- 4 years). A further 6 patients of the ECD group had no success in performing the labyrinth test. The CVD group was not different from the control group in making errors, but slower (p less than 0.05). The labyrinth test is found suitable for a more precise diagnosis of early cognitive deficit in the early stage of a primary degenerative dementia of the Alzheimer type. PMID- 2227468 TI - Medical correlates of agitation in nursing home residents. AB - This paper examines the relationship between agitation and medical and psychiatric diagnoses. Agitation marked by aggressive behaviors (e.g., hit, kick) was related to dementia and impairments in activities of daily living. Physically nonaggressive behaviors (e.g., pacing, disrobing inappropriately) correlated with cognitive impairment, fewer medical diagnoses, and absence of a hearing loss. Verbally agitated behaviors (e.g., constant complaints) were manifested by residents with more physical diagnoses, mental disease (other than schizophrenia and affective disorders), more reported pain, and higher cognitive functioning than the population as a whole. PMID- 2227469 TI - Features of multiple sclerosis in older patients in South Wales. AB - Multiple sclerosis (MS) may occur outside the commonly accepted age range. Data relating to features of MS in a population in South Wales have been analysed to find features which characterise older patients. The older patients are more severely disabled due to the accumulation of visual defects and motor signs and symptoms. The course of the disease is marked by single localised attacks with long remissions. Those with onset over 50 years deteriorate more rapidly, but in those who were over 50 at the time of interview, this did not occur. It is suggested that there is no essential difference in MS in older patients, but there may be features which reflect normal ageing and diseases commoner in old age. PMID- 2227470 TI - Monokine production by malnourished nursing home patients. AB - Protein malnutrition is associated with a decreased febrile and acute phase response to infection and increased mortality. To elucidate a cause for this poor response, we assessed the effect of chronic protein malnutrition on monocyte production of the pyrogens interleukin-1 (IL-1) and tumor necrosis factor (TNF). Thirteen malnourished nursing home residents, 11 age-matched controls, and 9 young controls were studied. Production of IL-1 and TNF in vitro was not diminished in the malnourished group when compared with the age-matched and young controls. Causes other than diminished IL-1 or TNF production should be sought to explain decreased resistance to infection in the malnourished nursing home resident. PMID- 2227471 TI - Hypernatraemia in the elderly patient. AB - The elderly are at risk of developing hypernatraemia because of age-related changes in renal function and body composition. The pathophysiology and aetiology of hypernatraemia are reviewed with emphasis on iatrogenic factors. A rational approach to management is discussed and clear guidelines for treatment described. PMID- 2227472 TI - Consideration of spatial orientation mechanisms as related to elderly fallers. PMID- 2227473 TI - Behavioral training for stress and urge incontinence in the community. AB - Behavioral training procedures provide an effective, low-risk approach to the treatment of persistent urinary incontinence. This paper describes the use of biofeedback techniques for the operant conditioning of physiological responses, such as selective contraction of pelvic floor muscles and voluntary inhibition of detrusor contraction, that mediate bladder control. The effectiveness of biofeedback-assisted behavioral training for most independent-living older adults is documented in several research studies. The data indicate that behavioral treatment of stress or urge incontinence results in improvement rates which range from 78 to 94%. The role of biofeedback in behavioral training and its practicality for use in office practice are also discussed. PMID- 2227474 TI - Urinary incontinence in old age: helping the general practitioner to make a diagnosis. AB - Since urinary incontinence is one of the major presenting symptoms of illness in old age, all those who deal with this professionally should have a clear plan in mind as to how to proceed with diagnosis and management. Such a plan is outlined here based first of all on history and examination and easily performed tests and followed, if the problem still remains, by an empirical approach based on the major presenting symptom--urge incontinence, stress incontinence or incontinence of which the patient is unaware. PMID- 2227475 TI - Noninvasive diagnosis of the patient with complex incontinence. AB - Even in complex cases, the cause of incontinence can usually be discerned noninvasively. The author outlines one such approach, focusing on helpful diagnostic points that can be elicited without sophisticated urodynamic techniques. PMID- 2227476 TI - [From Helmholtz' eye mirror to the fundus camera. Ophthalmoscope and related instruments of the Museum of Medical History of the Zurich University]. PMID- 2227477 TI - Rapid assessment of the visual field in glaucoma using an analysis based on multiple correlations. AB - We wished to determine which areas of the visual field contribute most strongly and most frequently to the deterioration of the visual fields in patients with high ocular pressure. The computerized analysis, using linear and multiple regressions of the findings in 382 visual fields, allowed us to select four test points sensitive enough to estimate the actual global sensitivity of the central visual field (correlation coefficient, 0.98). This system also allowed us to estimate the number of pathological points and even to classify accurately over 75% of the cases in terms of their normal or pathological condition, as well as to determine the depth of the defect. The remaining cases show that the deterioration, if it exists, is not significant. Requiring less than 1 min a threshold examination at these four test points enables us to acquire greater insight into the glaucomatous defect. PMID- 2227478 TI - Congenital nonpigmented epithelial iris cyst removed by block-excision. AB - A 1-month-old white girl developed a rapidly progressing congenital nonpigmented iris cyst covering the pupil and displacing the lens and ciliary body. The cyst was completely removed using a modified block excision (9 x 3.5 mm). The tumor consisted of partially keratinizing cuboidal epithelium with goblet cells, which was covered by proliferating corneal endothelium on the outside. Histopathological, and scanning and transmission electron microscopic findings are described. The postoperative course is unremarkable for 1 year. To our knowledge this case is the first case of a congenital iris cyst successfully treated with block-excision. PMID- 2227479 TI - Presence and distribution of fibronectin on the surface of implanted intraocular lenses in rabbits. AB - An immunohistochemical study was performed to observe cellular proliferation on the surface of implanted intraocular lenses (IOLs) in rabbit eyes. Rabbits were killed at intervals of 3 days and 1, 2, and 4 weeks after the operation. The IOLs were removed and examined by an immunoperoxidase staining method using antifibronectin (anti-FN) antibodies. The FN immunoreactivity was detected in macrophages and giant cells attached to the IOL surface. Prominent staining was observed in these cells 1 week after the operation, and staining for FN was less intense in the specimens obtained 2 and 4 weeks after implantation. These findings suggest that FN is produced by macrophages and giant cells on the IOL surface and may play an important role in cellular adhesion and motility. FN immunoreactivity decreased with time, which might be related to cellular activity. PMID- 2227480 TI - Vertical rectus muscle transposition with intraoperative botulinum injection for treatment of chronic sixth nerve palsy. AB - Six adult patients with acquired, chronic, complete sixth nerve palsy had vertical rectus muscle transposition to the lateral rectus muscle insertion with intraoperative injection of botulinum toxin into the ipsilateral medial rectus muscle. Five of six patients were orthophoric in primary gaze, and the remaining patient achieved single binocular vision with a small head turn. This method compares favorably with previously described transposition procedures for sixth nerve palsy in terms of amount of correction and size of the window of single binocular vision with a lower risk of anterior segment ischemia. PMID- 2227481 TI - Intraocular pressure in patients with Cushing's disease. AB - Externally applied corticosteroids increase the intraocular pressure in one-third of the general population. We evaluated the intraocular pressure in 62 patients with endogenously elevated serum cortisol levels due to hypothalamic pituitary dependent Cushing's disease. All patients underwent transphenoidal microsurgical sella exploration within 4 years after the onset of subjective symptoms. The intraocular pressure (preoperative mean, 14.9 +/- 3.5 mm Hg) exceeded 21 mm Hg in four eyes before surgery and in one eye after surgery (postoperative mean, 14.3 +/- 2.8 mm Hg). In patients attaining postoperative remission and whose pressure readings were taken at least 3 months after surgery, the postoperative intraocular pressure was significantly (P = 0.04) lower than that measured preoperatively (14.2 +/- 2.7 vs 13.0 +/- 2.0 mm Hg). Biomorphometry of the optic disc topography and the retinal nerve-fiber layer in 19 patients revealed no glaucomatous changes. In contrast to topically applied corticosteroids, endogenously elevated serum cortisol levels in patients with hypothalamic pituitary-dependent Cushing's disease increased intraocular pressure only slightly, with no great risk of glaucomatous optic nerve damage. PMID- 2227482 TI - Pattern electroretinograms in optic neuritis during the acute stage and after remission. AB - A total of 20 patients with unilateral acute optic neuritis were studied. Each patient had experienced the recent onset of a decrease in visual acuity, a relative afferent pupillary defect, a relative or absolute central scotoma and a colour-vision defect. The pattern-reversal electroretinogram (PERG) of each patient was analysed with regard to the amplitude of the positive and negative components. During the acute stage the amplitude of the positive component was reduced in all patients and that of the negative, in 18 of 20 cases. Parallel to clinical recovery, a steady increase was observed in the amplitude of the positive component to normal values; no statistical differences between affected and fellow eyes was found. In contrast, the amplitude of the negative component remained significantly reduced after clinical recovery. PMID- 2227483 TI - Temporary silicone oil tamponade in the treatment of complicated diabetic retinal detachments. AB - A retrospective study is reported on 132 eyes with retinal detachment, resulting from advanced proliferative diabetic retinopathy, treated using vitrectomy techniques and silicone oil tamponade. Epiretinal surgery was performed using a bimanual technique. Silicone oil was removed in 64 eyes (49%) which regained an improved final vision of 5/200 or better. In 17 eyes (13%), vision was improved but silicone oil could not be removed. It is expected that the function of several of these eyes will eventually deteriorate because of progressive silicone induced glaucoma. The remaining 51 eyes (38%) were surgical and functional failures. PMID- 2227484 TI - Retinal break type and proliferative vitreoretinopathy in nontraumatic retinal detachment. AB - In a retrospective study of 1180 consecutive eyes operated for retinal detachment, vitreous traction on the rent was the determining factor for the development of proliferative vitreoretinopathy (PVR). Round, multiple, small holes in equatorial degeneration (retinogenic) and macular holes in which no vitreous traction on the rent was found did not complicate with PVR. Retinal detachment caused by horseshoe or crescent-shaped tears with evidence of vitreous traction (vitreogenic) developed PVR to a variable degree: in 171 (25.8%) senile myopic, 19 (44.2%) senile-myopic aphakic, 23 (20.2%) typical aphakic, and 32 (78.1%) patients with giant tears. We also found that retinogenic retinal detachments affected younger age groups more than did vitreogenic retinal detachments. PMID- 2227485 TI - New and recurrent tumor foci following local treatment as well as external beam radiation in eyes of patients with hereditary retinoblastoma. AB - The study is based on a retrospective analysis of data from 200 patients with hereditary retinoblastoma. Apart from four unilateral cases with a positive family history all patients had bilateral disease; 229 appeared suitable for conservative treatment while 167 eyes had to be enucleated. Primary local treatment was performed in 102 eyes, while 127 eyes received primary external beam radiation using a linear accelerator. Follow-up was adjusted by life tables, with 75% of the patients being observed longer than 2 years. Using life-table statistics new and recurrent tumors were found in 41% of all patients and in 95% of these cases they were noted within 26 months after initiation of therapy. Among eyes treated with primary external beam radiation new and recurrent tumors were observed significantly less frequently when 50 Gy (22% compared with 49% after 40 Gy) and a highly accurate beam alignment technique (22% compared with 48% after alignment to the outer bony canthus) were applied. The incidence of recurrent tumors following primary local treatment did not differ significantly with regard to the application of either photo- or cryocoagulation (28% vs 33%), while no recurrence was observed among tumors that were suitable for primary treatment using ruthenium or cobalt plaques. PMID- 2227486 TI - X-linked congenital retinoschisis. AB - The natural history and electrophysiological findings of 52 patients with X linked congenital retinoschisis with a follow-up of up to 26 years are described. The mean visual acuity was reduced to 0.24 +/- 0.2 and remained unchanged in most patients during this time. If visual loss occurred, it usually happened in the first decennium. The complications were retinal detachments in 11% and vitreous hemorrhages in 4% of the eyes. In general, the vitreous hemorrhages resolved spontaneously. Retinal detachments were treated successfully with conventional buckling procedures. Redetachments occurred in about 40%. Prophylactic laser coagulation was of no use because it was complicated by detachment in 43% of our series. The electro-oculogram was usually normal. In addition to the known electrorentinographic findings of normal a-wave and reduced b-wave amplitudes, we found prolonged b-wave latencies and implicit times, as well as a reduced 30 Hz flicker response. PMID- 2227487 TI - Macular detachment following laser treatment for proliferative diabetic retinopathy. AB - Case records of patients who had macular detachment following argon laser photocoagulation for proliferative diabetic retinopathy were reviewed. Thirteen eyes of 11 patients out of a total of 480 patients treated had this complication, and in 12 eyes of 10 patients the short latency suggested a true precipitating effect. This represents 2.1% of patients receiving panretinal photocoagulation. Patients with detachment were younger and developed diabetes earlier than the controls (P less than 0.025), and the detached eyes had received more numerous laser burns on average per session than the controls (P less than 0.001). In 5 eyes the last photocoagulation dose exceeded 1000 burns delivered in the presence of traction membranes in an attempt to arrest continuing neovascular proliferation not responding to earlier more moderate treatment. Only 1 eye had received early, extensive and repeated photocoagulation. Vigorous treatment at an early stage of the proliferation may prevent this complication, although the advantages or disadvantages of fractionation of photocoagulation will only be shown by a prospective trial. PMID- 2227488 TI - Retinal circulation times in quantitative fluorescein angiography. AB - We tried to obtain an overview of the quantitative state of the retinal circulation. Optical density measurements by an image analyzer were performed on video fluorescein angiograms for the determination of dyedilution curves. To ensure that curves with a sharp peak were obtained, 1 ml sodium fluorescein 10% was flushed with 20 ml physiological saline. From dilution curves of a retinal circulation times, T(x) (x = 1, 25, 50, 75, and 100) and Tm, were calculated. T(1) corresponds to the difference in the time of initial dye appearance; T(50), to the so-called half-maxim time difference; T(100), to the difference in the time to peak intensity; and Tm, to the mean circulation time. T(50) showed the best reproducibility when it was examined at 49 retinal regions of 10 healthy volunteers with a double video-fluorescein angiogram that was obtained within 1 min. Normal values (mean +/- SD) at the temporal superior region of 37 healthy volunteers were as follows: T(1) = 0.87 +/- 0.66 s, T(25) = 1.52 +/- 0.48 s, T(50) = 1.83 +/- 0.50 s, T(75) = 2.12 +/- 0.56 s, T(100) = 2.73 +/- 0.76 s, and Tm = 2.69 +/- 1.25 s. We believe that these values give a general overview of the quantitative state of normal retinal circulation. PMID- 2227489 TI - Evaluation of the 701 interzeag lens opacity meter. AB - The Interzeag 701 Lens Opacity Meter was used to study the lenses of 122 cataract eyes and 73 healthy eyes with clear lenses. The readings taken separately in 67 eyes by two different operators did not significantly differ. Statistically significant differences were found between the readings taken by the same operator when the pupil size was different in all types of cataract and also in eyes with transparent lenses. Opacity Meter readings correlate well with the visual acuity of eyes with nuclear and mixed cataracts, but no correlation was found in eyes with cortical or posterior subcapsular cataracts. In healthy eyes with clear lens, a correlation was found between the instrument readings and age. PMID- 2227490 TI - Hemianopic offsets in the visual field of patients with glaucoma. AB - In 359 glaucoma patients (600 eyes), we measured the peripheral field with kinetic targets and the central 30 degrees field of vision with static testing, using the Field-master-5000 automated perimeter to evaluate the prevalence and significance of step-like visual-field defects along the vertical midline (a hemianopic offset). In all, 129 eyes of 121 patients had a hemianopic offset. In 108 eyes the offsets (involving either the peripheral or the central field or both) were associated with other glaucomatous field changes, whereas 21 eyes showed a peripheral offset as an isolated finding. Of the 8 cases of offsets found in both eyes, 7 were binasal and 1 occurred bitemporally but in separate hemifields. This study suggest that hemianopic offsets occur commonly in glaucoma patients but have limited diagnostic value because most are associated with other glaucomatous field changes. However, these findings help in distinguishing glaucomatous offsets from those caused by neurological lesions. PMID- 2227491 TI - Static threshold variability in the peripheral visual field in normal subjects. AB - We assessed the variability of point-wise static threshold values and the components of fluctuation outside the central 30 degrees field in 20 normal individuals tested on the Humphrey field analyzer. We found a mean short-term fluctuation of 2.37 dB, a long-term heterogeneous fluctuation of 5.28 dB, and a long-term homogeneous fluctuation of 1.10 dB. All components of fluctuation were greatest superiorly. Point-wise variation was highest superiorly and nasally and increased with greater eccentricity from fixation in all but the temporal quadrant. Also, point-wise variation was greater between individuals than between tests in a single individual. This study suggests that outside the central 30 degrees field, changes in individual threshold measurements in the superior and nasal quadrants should be greater than those in the temporal or inferior quadrants before they can be distinguished from normal variation. PMID- 2227492 TI - External eye flora as a nutrient source for Acanthamoeba. AB - Certain bacteria cause excystment of Acanthamoeba from cyst to trophozoite form and are then ingested by migrating trophozoites. We studied the response of Acanthamoeba cysts to inoculation on agar seeded with three types of commensal eye bacteria and Escherichia coli. Amoebae excysted on all bacteria tested, and the migration rate of Acanthamoeba trophozoites on each was compared. Acanthamoeba migrated with equal speed on E. coli and Staphylococcus epidermidis. Migration was observed, but was more slow on Micrococcus and Corynebacterium. Commensal bacteria on the eyelids, conjunctiva and tear film may have a role in pathogenesis of Acanthamoeba keratitis. PMID- 2227493 TI - Panretinal photocoagulation aggravates experimental proliferative vitreoretinopathy. AB - The effects of panretinal photocoagulation (PRP) on intravitreal proliferation were evaluated in an experimental model for proliferative vitreoretinopathy (PVR). Thirty-three pigmented rabbits underwent argon laser PRP in one eye. Cultured fibroblasts (2 x 10(5) or 4 x 10(5) cells) were implanted into the intact vitreous of both eyes of each animal either 3 days after PRP (when acute laser lesions were present) or 4 weeks after PRP (scarred laser lesions). PVR was assessed by indirect ophthalmoscopy for 4-8 weeks. Histological examination included staining with monoclonal antibodies against glial fibrillary acidic protein (GFAP). In both groups significantly more severe stages of PVR developed after PRP than in the controls. Total retinal detachments ensued in 13 photocoagulated eyes versus five controls. PRP induced invasion of macrophages, proliferation of retinal pigment epithelium and a conspicuous Muller cell response, enhancing intraocular inflammation, which stimulated intravitreal proliferation and aggravated PVR. PMID- 2227494 TI - Muller cells in detached human retina express glial fibrillary acidic protein and vimentin. AB - We investigated the expression of vimentin and glial fibrillary acidic protein (GFAP) within Muller cells in normal human retinas and in detached human retinas of proliferative vitreoretinopathy (PVR) cases using the immunogold method. Muller cells in normal retinas showed vimentin immunoreactivity and faint GFAP immunoreactivity; however, in detached retinas they showed distinct GFAP immunoreactivity as well as vimentin immunoreactivity. Immunoelectron microscopic observation revealed that intermediate filaments (IF) within Muller cells in normal retinas showed vimentin immunoreactivity and that those within Muller cells in detached retinas showed both vimentin and GFAP immunoreactivity. Double staining for vimentin and GFAP showed that in detached retinas, these two protein immunoreactivities were observed in the same filaments. These results indicate that IF of human Muller cells consist of vimentin under normal conditions and that Muller cells in detached retinas contain different IF, which consist of vimentin and GFAP. PMID- 2227495 TI - Toxicity and clearance of intravitreal cefotetan. AB - Direct intravitreal injection of antibiotics plays an important role in the management of bacterial endophthalmitis. In the present study we investigated the toxicity and clearance of intravitreally injected cefotetan in a rabbit model. No toxic ocular side effects could be detected by electroretinography (ERG) or light and electron microscopy up to and including a single intravitreal dose of 1000 micrograms. Intravitreal injection of 2000 micrograms cefotetan resulted in mild degeneration of photoreceptor outer segments and, sporadically, in cataract formation. After intravitreal injection of 4000 micrograms, moderate toxic degeneration of photoreceptors occurred, with displacement and mitochondrial swelling of inner segments. In addition, lysosomal lamellar inclusion bodies could be detected in pigment epithelial cells. After a single intravitreal injection of 1000 micrograms cefotetan, concentrations greater than the minimum necessary for the inhibition of most commonly occurring intraocular pathogens (except Pseudomonas aeruginosa and Staphylococcus epidermidis) were maintained in the vitreous humor for greater than 48 h. Cefotetan may be a potentially important drug for intravitreal injection, especially in cases of gram-negative and suspected anaerobic endophthalmitis. PMID- 2227496 TI - Clinicopathological findings 11 months after implantation of a functioning aqueous-drainage silicone implant. AB - An aqueous-drainage silicone device was implanted in a 57-year-old diabetic patient with neovascular glaucoma after failure of conventional therapy. Postoperative intraocular pressure (IOP) was well controlled, ranging between 10 and 20 mm Hg without the use of supplemental agents. Despite the normal IOP, the eye became painful and amaurotic 11 months after implantation due to progression of the retinopathy accompanied by the development of severe tractional retinal detachment. Enucleation was performed and the eye underwent histopathological examination. The filtering bleb around the silicone plate of the implant on the equatorial sclera was lined with a thick layer of collagenous connective tissue. Numerous microcystic spaces could be seen in the bleb wall by light microscopy. Electron microscopy confirmed this finding; in addition, only a meshwork of collagen fibre-like bundles was visible at some areas of the innermost bleb wall. Control of IOP in spite of bleb fibrosis in this particular case may have been due to a loss of matrix components and to the formation of microcystic spaces in the bleb wall, which seem likely to be channels for the passage of aqueous humor. PMID- 2227497 TI - Ultrastructural pathology of anterior persistent hyperplastic primary vitreous. AB - Using transmission electron microscopy, the fine structure of anterior persistent hyperplastic primary vitreous (PHPV) removed from the eyes of four infants was studied. The tissue mass was composed of vessels derived from or representing the tunica vasculosa lentis posterior and the vasa hyaloidea propria. They were embedded in a loose connective-tissue matrix containing many fibroblasts and mature collagen fibrils. Toward the posterior surface, the fibroblasts became more numerous, elongated and densely packed. At the point of its entry into the posterior pole of the mass, the hyaloid artery was found to be surrounded by glial cells, probably representing an extension of the wall cells of the hyaloid canal. Venous drainage of the PHPV nodules seemed to occur via the ciliary body to which they were connected by tiny vessels bridging the distance from the PHPV lump to elongated ciliary processes. The anterior surface of the tissue lump was covered with lens fragments. These remnants showed signs of very early disturbance of lens development, with a failure to form posterior lens fibers. Based on these findings, the authors suggest that PHPV may be secondary to a primary defect in lens development. PMID- 2227498 TI - Evaluation of the functional results after different techniques for treatment of retinal detachment due to macular holes. PMID- 2227499 TI - [Ecological and hygienic concepts of human nutrition]. AB - The paper presents data on the development of eco-hygienic concept of human nutrition. The scheme of migration of various xenobiotics and biological contaminants along the food chain is given. The necessity for the substantiation of unified MACs of alien substances for all eco-systems is indicated. The ++eco hygienic concept of nutrition should be directed at the protection (purity) of the inner human environment and normalization of the processes of its activity in interrelations with the environment. PMID- 2227500 TI - [Changes in biological activity of turf-podzolic soil of different mechanical composition contaminated with heavy metals]. AB - It has been shown that soil pollution with heavy metals (copper, nickel) lead to negative changes in parameters characterizing potential biological activity of soil (nitrogen-fixation, breath, invertase activity, bacteria and fungi count). More profound changes were observed in sandy soil compared to loamy soil. A direct relationship of these effects with the content of mobile forms of heavy metals in soil has been established. For the comparative and prognostic investigation of the danger of soil pollution with heavy metals it has been suggested to use a coefficient of differences in the content of mobile forms and a coefficient of biological effect. PMID- 2227501 TI - [Monitoring of xenobiotics in food products and daily diets (review of the literature)]. PMID- 2227502 TI - [Hygienic examination of oranges subjected to electro-ion treatment for the prolongation of preservation time]. AB - On the basis of large experimental material (study of organoleptic properties, chemical composition of electro-antiseptic + oranges, microbiological studies of microbic cenosis during their storage, biological experiments to find out the possible general toxic effect of the pretreated fruit on animal organism) safety of oranges subjected to electro-ion++ treatment to prolong the term of preservation has been stated. The possibility to use electro-atiseptic oranges by the people in their nutrition has been proved. PMID- 2227503 TI - [Psychological adaptation of older workers to occupational conditions]. AB - As a result of ergometric investigation of labour activity of 187 workers of mass professions (machine-operators, metal craftsmen, fitters), involved in physical labour of medium heaviness, the following age patterns in behavioral self regulation of activity were detected in people of 20-79 years of age: reduction of the occupation in the major jobs and increase in the occupation in the auxiliary, less tense jobs, decrease in the density of work time, changing in the activity strategy, reduction of the duration of continuous work and increase of the duration of the subsequent rest, dividing of the alloted volume of work into parts. Physiological rationalization of labour of older workers based on the established patterns of their behavioral adaptation to labour is a sufficiently effective measure for labour rehabilitation and lengthening of the period of active life. PMID- 2227504 TI - [Ways of increasing the operational and protective properties of anti-mercury respirators]. AB - The major results of studies on the assessment of the dynamic activity of sorption--filtering respirators relative to mercury vapours are presented. It has been shown that the term for the storage of the respirator "Lepestok-G" can be increased from 6 months, starting from the date of production--according to the established technical rules, --up to 2 years. The surface density of the sorbent can be reduced from 3.5 down to 1.5 mg/sm2, which will make it possible to significantly reduce the initial resistance to breathing and to improve the operational and protective properties of the respirator. PMID- 2227505 TI - [Interrelations between functional changes and health status and climatic factors of Extreme North (review)]. PMID- 2227506 TI - [Mobility of cesium-137, sodium and potassium in different types of soil and prediction of cesium-137 accumulation in agricultural plants]. AB - Mobility of caesium-137, sodium and potassium in the natural environment in podzolic gray and chernozem medium-loamy, sward podzolic sandy soils and chernozem has been studied. Durability of fixation of caesium-137 increases in a number of soils: sward-podzolic sandy, podzolic loamy soils, chernozem. Caesium 137 concentration in agricultural plants is reduced along with the increase of caesium-137 fixation in soils and increase of the level of metabolic potassium. Coefficients of transition of metabolic caesium-137 by potassium and sodium, and of sodium by potassium. The mentioned above coefficients can be used for the prediction of caesium-137 cumulation in plants. PMID- 2227507 TI - [Effect of inhalation of trichlorobenzene and normal paraffins on the behavior of plutonium-239 in the rat body]. PMID- 2227508 TI - [Sanitary-protective and limitation areas for antennae of the decameter range]. AB - A detailed overview of a transmitting antenna of the decameter range is provided. It is shown that the field near such antennas has rather a complex structure. A comparative analysis of the existing design techniques for the determination of electromagnetic field intensity has been undertaken. On the basis of numerical design techniques the procedure of automated prediction of the electromagnetic situation is proposed. The basic components of the procedure are set forth. As illustrated by some antennas the dependence of sanitary and limitation zones on the wavelength, radiated power and the type of soil has been studied. PMID- 2227509 TI - [Hygienic regulation of static electric field generated by devices with electron ray tube]. AB - When detecting and hygienically assessing the static electric field generated by the devices with a half-tone storage tube it is necessary to take account of the impact of a number of characteristics of field intensity ranging on the obtained results. Taking into consideration the above characteristics during the research permits to lower error in the derived values and approximate them to the characteristics affecting the organisms of those using devices with a half-tone storage tube. PMID- 2227510 TI - [Substantiation of the tactics of short-wave ultraviolet irradiation of the air in hospital premises]. AB - It has been found out, that the level of microbic dissemination of the air of premises for the treatment of children increases 3-10 times following carrying out various functional activities in them. To reduce air contamination it is reasonable to use irradiation of bactericidal lamps of DB 30-1 type with specific power of 1.5 W/m3 for the first 20 min. after the work has been fulfilled in the premises. PMID- 2227511 TI - [Toxicokinetics of croneton]. PMID- 2227512 TI - [Relation between the inhibition of respiration of isolated liver mitochondria and the structure of copper and vanadium phthalocyanines]. PMID- 2227513 TI - [Evaluation of environmental effects of sewage water from sugar-processing factories used for irrigation of agricultural fields]. PMID- 2227514 TI - [A device for elimination of microorganisms from the air]. PMID- 2227515 TI - [Determining the levels of chloride ions in water solutions using a chloride selective electrode]. PMID- 2227516 TI - [Determining the activity of large radiation sources of arbitrary form]. PMID- 2227517 TI - [Threshold signaler of the gammaphone TIK-87]. PMID- 2227518 TI - [Various methodological approaches to evaluation of the cardiotoxic effect of pesticides in relation to the age factor]. PMID- 2227519 TI - [A method of preparing standardized gas mixtures of sulfur dioxide]. PMID- 2227520 TI - [Use of a new reagent azopyram for quality control of pre-sterilization of medical equipment]. PMID- 2227521 TI - [Problem of sorption of hydrofluoric acid with fibrous materials used for hemosorption]. PMID- 2227523 TI - [Problem of increasing the qualifications and special training of public health physicians and other specialists working in radiological subdivisions in Ukraine]. PMID- 2227522 TI - [Use of the method of the study of erythrocyte membrane permeability for urea for detecting the toxic effect of cyclohexylnitrate]. PMID- 2227524 TI - [Ways of improving the personnel organizational structure of the system of radiological subdivisions of the sanitary-epidemiological centers in Ukraine]. PMID- 2227525 TI - [Hygienic aspects and methodological basis for producing bioinert polymer materials with the properties for individual protection]. PMID- 2227526 TI - [V.I. Tatishchev on medicine]. PMID- 2227527 TI - Antioxidant enzymes and lipoperoxide in blood in uremic children and adolescents. AB - To determine whether oxidant-antioxidant balance is altered in chronic renal failure, antioxidant enzymes and lipid peroxide in peripheral blood cells and lipid peroxide in plasma were measured. Nine children and adolescents maintained on hemodialysis (HD), 9 on continuous ambulatory peritoneal dialysis (CAPD), and 14 controls were studied. Lipid peroxide was assayed fluorimetrically as thiobarbituric acid-reactive substances, superoxide dismutases by radioimmunoassays. Both manganese and copper-zinc superoxide dismutases in lymphocytes and monocytes in the HD and CAPD patients, and manganese superoxide dismutase in polymorphs in the HD patients were higher than in the controls. Copper-zinc superoxide dismutase, glutathione peroxidase, and catalase in erythrocytes were unaltered. The lipid peroxide level in plasma in the dialyzed patients was increased, whereas those in polymorphs and lymphocytes were unaltered. Triglyceride and total cholesterol in plasma in the dialyzed patients were also increased. The plasma lipid peroxide in the patients correlated with the triglyceride and total cholesterol level. This is the first study in which manganese superoxide dismutase is measured in nucleated cells of the patients with chronic renal failure. The present results suggest that increased superoxide dismutases protect against oxidative stress induced by chronic renal failure in nucleated cells but in neither erythrocytes nor plasma. PMID- 2227528 TI - Antioxidant action of ubiquinol homologues with different isoprenoid chain length in biomembranes. AB - Ubiquinones (CoQn) are intrinsic lipid components of many membranes. Besides their role in electron-transfer reactions they may act as free radical scavengers, yet their antioxidant function has received relatively little study. The efficiency of ubiquinols of varying isoprenoid chain length (from Q0 to Q10) in preventing (Fe2+ + ascorbate)-dependent or (Fe2+ + NADPH)-dependent lipid peroxidation was investigated in rat liver microsomes and brain synaptosomes and mitochondria. Ubiquinols, the reduced forms of CoQn, possess much greater antioxidant activity than the oxidized ubiquinone forms. In homogenous solution the radical scavenging activity of ubiquinol homologues does not depend on the length of their isoprenoid chain. However in membranes ubiquinols with short isoprenoid chains (Q1-Q4) are much more potent inhibitors of lipid peroxidation than the longer chain homologues (Q5-Q10). It is found that: i) the inhibitory action, that is, antioxidant efficiency of short-chain ubiquinols decreases in order Q1 greater than Q2 greater than Q3 greater than Q4; ii) the antioxidant efficiency of long-chain ubiquinols is only slightly dependent on their concentrations in the order Q5 greater than Q6 greater than Q7 greater than Q8 greater than Q9 greater than Q10 and iii) the antioxidant efficiency of Q0 is markedly less than that of other homologues. Interaction of ubiquinols with oxygen radicals was followed by their effects on luminol-activated chemiluminescence. Ubiquinols Q1-Q4 at 0.1 mM completely inhibit the luminol activated NADPH-dependent chemiluminescent response of microsomes, while homologues Q6-Q10 exert no effect. In contrast to ubiquinol Q10 (ubiquinone Q10) ubiquinone Q1 synergistically enhances NADPH-dependent regeneration of endogenous vitamin E in microsomes thus providing for higher antioxidant protection against lipid peroxidation. The differences in the antioxidant potency of ubiquinols in membranes are suggested to result from differences in partitioning into membranes, intramembrane mobility and non-uniform distribution of ubiquinols resulting in differing efficiency of interaction with oxygen and lipid radicals as well as different efficiency of ubiquinols in regeneration of endogenous vitamin E. PMID- 2227529 TI - Multiple actions of superoxide dismutase: why can it both inhibit and stimulate reduction of oxygen by hydroquinones? AB - Superoxide dismutase can either inhibit or stimulate autoxidation of different hydroquinones, suggesting multiple roles for O2.-. Inhibitory actions of superoxide dismutase include termination of O2.(-)-propagated reaction chains and metal chelation by the apoprotein. Together, chelation of metals and termination of O2.(-)-propagated chains can effectively prevent reduction of oxygen. Chain termination by superoxide dismutase can thus account for negligible accumulation of H2O2 without invoking a superoxide:semiquinone oxidoreductase activity for this enzyme. One stimulatory action of superoxide dismutase is to decrease thermodynamic limitations to reduction of oxygen. Whether superoxide dismutase inhibits or accelerates an autoxidation depends on the reduction potentials of the quinone and the availability of metal coordination for inner sphere electron transfers. PMID- 2227530 TI - Role of oxidatively modified LDL in atherosclerosis. AB - Oxidative modification of LDL is accompanied by a number of compositional and structural changes, including increased electrophoretic mobility, increased density, fragmentation of apolipoprotein B, hydrolysis of phosphatidylcholine, derivatization of lysine amino groups, and generation of fluorescent adducts due to covalent binding of lipid oxidation products to apo B. In addition, oxidation of LDL has been shown to result in numerous changes in its biologic properties that could have pathogenetic importance, including accelerated uptake in macrophages, cytotoxicity, and chemotactic activity for monocytes. The present article summarizes very recent developments related to the mechanism of oxidation of LDL by cells, receptor-mediated uptake of oxidized LDL in macrophages, the mechanism of phosphatidylcholine hydrolysis during LDL oxidation, and other biologic actions of oxidized LDL including cytotoxicity, altered eicosanoid metabolism, and effects on the secretion of growth factors and chemotactic factors. In addition, this review will examine the evidence for the presence of oxidized LDL in vivo and the evidence that oxidized LDL plays a pathogenetic role in atherosclerosis. PMID- 2227531 TI - HPLC procedure for the pharmacokinetic study of the spin-trapping agent, alpha phenyl-N-tert-butyl nitrone (PBN). AB - Considerable progress has been made in the use of spin-trapping agents for the trapping of free radicals in biological systems. Radicals have been detected in both in vitro and in vivo systems using this methodology. Free radicals have not only been identified by this procedure, but also the intensity of radical generation and the duration of their production has been assessed as well. One of the most widely used spin-trapping agents in biological systems is PBN. This spin trap appears to be relatively nontoxic at the levels required for successful trapping experiments, but there is no information concerning the possible fate of PBN in such biological systems. Metabolism of PBN could alter the concentration of PBN at the site of trapping which may affect the efficiency of radical capture, especially in in vivo systems. In this study, PBN was administered intraperitoneally to rats and the concentration of the spin trap in various organs was determined by high pressure liquid chromatography as a function of time (15 min to 12 h). The concentration of PBN in plasma peaked at 15 min while the maximum in all organs tested occurred at 30 min. The time course of PBN concentrations in all tissues followed similar curves, and declined rather steeply after the 30-min maximum with a biological half-life of 134 min. However, the amount of PBN per gram of tissue was always higher in liver and kidney than in the brain, heart, and lung. PBN was detected in the urine for as long as 24 h after injection of the compound. PMID- 2227532 TI - Oxidative damage and repair. The 5th biennial meeting of the International Society for Free Radical Research. November 14-20, 1990, Pasadena, California. Abstracts. PMID- 2227533 TI - [Personal view of the use of disposable syringes for analgesia in dentistry]. AB - After a synthetis of the main infectious illness transmittable through the oral cavity, the authors describe the experimental use of a new disposable syringe in dentistry. On the basis of a total of 160 local injections for dental interventions, the authors can say that this instrument allows to operate with a maximum of safety for the absolute absence of a direct infection, also by the simple salivary mean, between patients. More advantage come from the risk drop of needle puncture for the dentist and the assistants and for the automatic autoaspiration the syringe is provided which. PMID- 2227534 TI - [Emergencies in ambulatory dentistry]. AB - The most frequent critical situations that could happen in outpatient dental practice are analyzed and emergency treatment is proposed. Further, a full emergency set (both drugs and devices) is proposed as standard dotation. PMID- 2227535 TI - Age migraine and achievement motivation related? A psychophysiological study of responses to real-life achievement stress in young headache sufferers. AB - Achievement motivation and its physiological correlates were studied in 37 young migrainous headache sufferers (30 females and 7 males) and in 37 matched controls. Temporal and digital pulse amplitude, the EMGs of the m. frontalis, anterior temporalis and corrugator supercilii, heart and respiration rate, head temperature and electrodermal activity were measured during an adaptation session, an examination and an intelligence test. An abnormal response in the temporal artery, which was present in the migrainous headache sufferers, was not associated with achievement motivation. But the latter was positively associated with a high skin conductance level, a greater number of spontaneous skin conductance responses (SCRs) during the examination and a lower digital pulse amplitude in both the migrainous headache and control groups. Higher sympathetic activity in subjects with high achievement motivation was interpreted as an indication of greater mental effort and is a possible contributory factor to an attack in those with migraine. PMID- 2227537 TI - Diagnostics of cervicogenic headache. AB - Cervicogenic headache (CH) is a clearly defined headache syndrome and can usually be differentiated from other unilateral headaches like cluster headache, chronic paroxysmal hemicrania (CPH) and hemicrania continua by a thorough history and neurological examination. Combinations of CH with other headaches like migraine, tension headache, combination headache and drug induced headache, that occur quite frequently, can complicate the diagnosis. In our own material of 5520 headache patients the prevalence of CH was 13.8% (763). Four hundred and thirty of these patients suffered from CH in combination with one or more other headaches. PMID- 2227536 TI - The headache of challenge in our time: cervicogenic headache. AB - Cervicogenic headache is a unilateral headache without sideshift, beginning in the posterior of the head but ultimately spreading to the front. It is characterized by rather mild and protracted pain episodes, the pain in many instances eventually becoming chronic, but with an undulating course. There is a marked female preponderance. The special features indicating neck involvement include: whiplash trauma by history, reduction of range of movement in the neck, ipsilateral shoulder and--occasionally--arm pain, and, further, the fact that attacks can be precipitated mechanically by the patients (by neck movements) or by the physician (by external pressure towards circumscribed points in the neck). An important theoretical--and diagnostic--feature is the fact that the anaesthetic blockade of the major occipital nerve results in discontinuation of pain in an area (the oculo-frontal area) where anaesthesia has not been obtained. PMID- 2227539 TI - Proceedings of the 21st annual meeting of the Society of Gynecologic Oncologists. San Francisco, California, February 1990. PMID- 2227538 TI - The challenge of the 1990s. PMID- 2227540 TI - Adjuvant chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (PAC) for early-stage high-risk endometrial cancer: a preliminary analysis. AB - Between October 1985 and January 1989, 33 patients with stage I (31) or clinically occult stage II (2) endometrial cancer at a high risk for recurrence were entered in a prospective study evaluating adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy. Eligibility criteria included grade 2 tumors with middle- or outer-third myometrial invasion (16), grade 3 tumors with any degree of myometrial invasion (17), presence of extrauterine disease with no gross residual (17), or a high-risk histologic subtype including papillary serous (4), adenosquamous (5), or clear cell (1) tumors. Patients received PAC (50/50/500 mg/m2) at 4-week intervals for six cycles. Thirty patients (90%) completed therapy. Toxicity included severe neutropenia in 14 patients, neutropenic sepsis in 2 patients, and doxorubicin-related cardiomyopathy in 1 patient. There were no treatment deaths. Current median follow-up is 25 months. Nine patients (27%) have developed a recurrence, 7 of whom died, after a median interval of 14 months. Eight of the 9 with recurrence initially had extrauterine disease (P = 0.02). The resulting 2-year actuarial progression-free and overall survival rates were 79 and 83%, respectively. The median progression-free interval was 29 months for patients with extrauterine disease and 45+ months for those with no extrauterine disease (P = 0.02). These results suggest that a phase 3 randomized trial comparing adjuvant PAC with radiation therapy is warranted. PMID- 2227541 TI - Surgical-pathologic variables predictive of local recurrence in squamous cell carcinoma of the vulva. AB - One hundred and thirty-five patients with squamous carcinoma of the vulva were treated at UCLA and City of Hope Medical Centers between 1957 and 1985. Sixty-two cases were stage I, 48 stage II, 18 stage III, and 7 stage IV. Twenty-one patients developed a local vulvar recurrence after primary radical resection. Ninety-one patients had a surgical tumor-free margin greater than or equal to 8 mm on tissue section and none had a local vulvar recurrence. Forty-four patients had a margin less than 8 mm; 21 had a local recurrence and 23 did not (P less than 0.0001). Of the 23 patients with a margin less than 8 mm who did not recur locally, 14 remained free of disease, and 9 had either advanced disease, declining health, or short follow-up. Depth of invasion is associated with local recurrence, with a 9.1-mm reference value correctly predicting outcome in 81.5% of cases. Increasing tumor thickness is associated with local recurrence, with a 10-mm reference value predictive of 90% non-recurrence and 33% recurrences. A pushing border pattern is less likely to recur than an infiltrative growth pattern. Lymph-vascular space invasion has a combined predictive accuracy of 81.5%. Increasing keratin and greater than 10 mitoses per 10 high-power fields correlate with local recurrence. Neither clinical tumor size nor coexisting benign vulvar pathology correlates with local recurrence. Fourteen of twenty-one patients with vulvar recurrence died of metastatic disease, four died of intercurrent disease, and three were alive at 32, 68, and 157 months, with 16 recurring in less than 1 year. Surgical margin is the most powerful predictor of local vulvar recurrence. Combining factors in a stepwise logistical regression does not significantly improve this predictive value. Accounting for specimen preparation and fixation, a 1-cm tumor-free surgical margin on the vulva results in a high rate of local control, whereas a margin less than 8 mm is associated with a 50% chance of recurrence. PMID- 2227543 TI - Radical wide excision and selective inguinal node dissection for squamous cell carcinoma of the vulva. AB - Limited resection of some vulvar cancers may provide cure rates equivalent to those obtained with radical vulvectomy and bilateral inguinal node dissection. Rapid recovery, fewer complications, and better functional result have been described as advantages to less extensive procedures. Since 1978, 32 patients with invasive squamous cell cancer of the vulva (depth greater than 1 mm) and clinically negative inguinal lymph nodes underwent radical wide excisions as primary therapy. Mean age at diagnosis was 61 years. Seventeen patients had T1 and 15 had T2 tumors. Resection of the primary lesion was tailored to lesion location and size, and dissection was carried to the deep perineal fascia. Twenty two patients had unilateral superficial inguinal lymph node dissections, five with midline lesions had bilateral superficial dissections, and five had node samplings which included deep inguinal nodes. Depth of invasion ranged from 1.5 to 13.0 mm. Mean largest lesion dimension was 23 mm. Five-year lifetable survival for the entire group was 84%. Univariate analysis of potential prognostic variables showed no significant recurrence or survival differences for patient age (P = 0.56), symptom duration (P = 0.57), FIGO stage (P = 0.67), tumor grade (P = 0.20), tumor location (P = 0.26), depth of invasion (P = 0.56), or resection margin status (P = 0.63). Thirty-one percent of patients had perioperative complications, and 16% developed delayed complications. Mean hospital stay was 10 days. Three patients (10%) developed new or recurrent vulvar disease and underwent additional therapy. None have died of disease, although one is alive with persistent tumor. Radical wide excision and selective inguinal lymphadenectomy constitute a reasonable alternative to radical vulvectomy with bilateral inguinal node dissections for squamous tumors clinically limited to the vulva. Outcome may not be strongly influenced by lesion size or depth of invasion. PMID- 2227542 TI - Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy. AB - Attempting to improve local disease control in bulky (greater than 8 cm) primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix (stage II, 4; III, 10; IV, 6; recurrent, 9) were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients. PMID- 2227544 TI - Synergy is documented in vitro with low-dose recombinant tumor necrosis factor, cisplatin, and doxorubicin in ovarian cancer cells. AB - Ovarian carcinomas have been shown to be sensitive or insensitive to the in vitro exposure of several cytotoxic drugs and cytokines. Because of the potential for cytokines to enhance the efficacy of chemotherapeutic agents and to improve their therapeutic index, the optimal dose and schedule of the combination of these agents have been studied. We examined the cytotoxic effect of a combined modality using a variety of concentrations of recombinant tumor necrosis factor (rTNF) (a cytotoxic cytokine) with Adriamycin (ADR) and cisplatin (CDDP) on human ovarian carcinoma cell lines. Cytotoxicity was determined in a 24-hr 51Cr-release assay and confirmed in a 5-day viability culture assay. Five cell lines were used: PA 1, 222, OVCAR-3, SKOV-3, and OVCAR-8. Doses of rTNF that were minimally cytotoxic resulted in significant cytotoxicity and synergy when used with optimal or suboptimal concentrations of ADR or CDDP. This synergy was observed in four cell lines. Interestingly, the rTNF- and drug resistant SKOV-3 cell line was sensitive to the synergistic effect of Adriamycin and rTNF. The synergistic effect that was obtained was specific to rTNF, while the combined use of ADR and CDDP or recombinant interleukin-2 and cytotoxic drugs had no synergistic effect on tumor cell lysis. Further, the addition of anti-TNF antibody abrogated the synergistic effect seen with rTNF and the cytotoxic drugs. These studies demonstrate clearly that significant synergistic antitumor cytotoxic activity against human ovarian carcinoma cell lines can be achieved with combinations of low doses of rTNF and ADR or CDDP, suggesting their possible adaptation in vivo for cancer therapy. Further, the studies suggest that rTNF and the cytotoxic drugs tested may share a common lytic pathway. Since rTNF used alone has been relatively inactive in clinical trials, its potential activity may be apparent only when combined with conventional cytotoxic chemotherapeutic agents and when administered in relatively low concentration. PMID- 2227545 TI - c-myc amplification in ovarian cancer. AB - The c-myc oncogene codes for a DNA binding protein that appears to play an important role in the regulation of cell growth. c-myc gene amplification has been documented to occur in both hematopoietic and solid neoplasms and often indicates more biologically aggressive tumors. Southern hybridization analysis was performed on high-molecular-weight DNA isolated from primary ovarian carcinomas. Major structural rearrangements of c-myc were not detected. Five of seventeen (29.4%) tumor samples demonstrated amplification of the myc oncogene. The 5 patients with ovarian carcinomas associated with c-myc amplification exhibited a median survival of 17 months. Of the 12 patients without evidence of tumor-associated c-myc amplification, 5 have exhibited disease-free survival for an average of 36.8 months and are currently alive. The remaining 7 patients, the majority of whom had advanced-stage, poorly differentiated lesions with a normal c-myc copy number, exhibited a median survival of 9 months. There was no apparent relationship between c-myc amplification, grade of tumor differentiation, and response to platinol-based chemotherapy. These data do not suggest a prognostic role for c-myc amplification in primary ovarian cancer. However, c-myc amplification is a common finding in advanced-stage ovarian cancer. PMID- 2227546 TI - Diagnosis and treatment of pulmonary metastases from cervical carcinoma. AB - The records of 2116 patients treated for cervical malignancy from 1969 to 1984 at the University of Alabama at Birmingham were reviewed and 88 (4.16%) had pulmonary lesions consistent with metastatic cervical cancer. The data were analyzed to characterize risk factors for developing lung metastases, to determine radiographic patterns, to assess methods of documentation, and to determine response to chemotherapy. Platinum-type chemotherapy has a 67.7% response rate on chest X ray, with one-third of the responses being complete. The prognosis is poor with a median survival of 0.69 year (8.3 months); only 2 of these 88 patients were long-term survivors. Although the survival is poor, a few statistically significant factors could be identified as prognostic. Our data do not support use of surveillance chest X rays, as there is no statistically significant survival difference in symptomatic versus asymptomatic patients. The development of more effective salvage therapy may alter this recommendation. PMID- 2227547 TI - Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. AB - There were 732 evaluable patients with primary, previously untreated, histologically confirmed stage I squamous carcinoma of the cervix with greater than or equal to 3-mm invasion. Of these, 645 had no gross disease beyond the cervix/uterus, had negative paraaortic lymph nodes, and had undergone a radical hysterectomy with pelvic lymphadenectomy. The 3-year disease-free interval (DFIs) for the 545 patients with negative pelvic nodes was 85.6%, and for the 100 with positive pelvic nodes, 74.4%. A large number of pelvic nodes involved with tumor was not correlated with a poorer prognosis; the DFIs were 72.1, 86.4, and 64.6% for one, two, and three or more positive pelvic nodes, respectively. DFI correlated strongly with depth of tumor invasion, both in absolute terms (mm) and infractional thirds. The DFI was 94.6% for less than or equal to 5 mm, 86.0% for 6-10 mm, 75.2% for 11-15 mm, 71.5% for 16-20 mm, and 59.5% greater than or equal to 21 mm. In fractional terms, the DFI was 94.1% for superficial third, 84.5% for middle third, and 73.6% for deep third invasion. With respect to clinical tumor size, the DFIs were 94.8, 88.1, and 67.6% for occult, less than or equal to 3 cm, and greater than 3 cm, respectively. The DFI was 77.0% for those with positive capillary-lymphatic spaces (CLS) and 88.9% for those with negative CLS. Tumor grade and parametrial status correlated with DFI. DFI was not significantly different for age, disease status of the surgical margins, tumor description (e.g., exophytic), quadrant involved with tumor, uterine extension, and keratinizing status of tumor cells. Clinical tumor size, CLS, and depth of tumor invasion were independent prognostic factors. PMID- 2227548 TI - Aggressive chemosurgical debulking in patients with advanced ovarian cancer. AB - From July 1986 to June 1989, 43 evaluable patients with advanced ovarian cancer were treated on protocol with initial cytoreductive surgery, two courses of high intensity intravenous Cytoxan (1000 mg/m2) and cisplatin (120-200 mg/m2) chemotherapy, and repeat debulking laparotomy in an effort to maximize response to a subsequent four cycles of intraperitoneal platinum-based chemotherapy. Two patients were stage IIIA, 2 stage IIIB, 28 stage IIIC, and 11 stage IV. Five tumors were grade 1, 9 grade 2, and 29 grade 3. Thirty-eight (88%) patients had bulky tumor (5-25 cm) found at first laparotomy; 25 of these had greater than 1 cm residual after initial debulking. Following two cycles of intensive intravenous chemotherapy 18 of these 25 had greater than 1-cm disease found at second laparotomy; 12 of 18 underwent secondary cytoreduction to less than 1 cm. Thus, 30 of these 38 (79%) patients entered the intraperitoneal phase of the protocol with less than 1-cm disease. Four patients had 2- to 5-cm tumor at initial laparotomy; two of four were debulked to less than 1-cm residual. All four were found to have less than 1-cm disease at second laparotomy. This combination regimen was well tolerated. There was one treatment-related death. In sum, 42 of 43 patients had tumor greater than 2 cm at staging laparotomy and 38 (88%) had large, bulky disease (5-25 cm); 34 of 43 (79%) entered the intraperitoneal phase of the protocol with optimal (less than 1-cm) disease. Aggressive chemosurgical cytoreduction in patients with bulky advanced ovarian cancer can leave a large proportion of patients with minimal residual disease and maximize their chances of responding to subsequent intraperitoneal chemotherapy. PMID- 2227549 TI - Oncogene alterations in endometrial carcinoma. AB - The neu oncogene codes for a cell surface protein that has a high degree of homology with the epidermal growth factor receptor. Amplification of this oncogene in breast carcinoma and ovarian carcinoma is correlated with a poorer prognosis. The c-myc oncogene codes for a DNA binding protein and is believed to regulate cellular proliferation. Sixteen primary endometrial adenocarcinomas were analyzed for c-myc and c-neu amplification. Eleven of sixteen tumor samples exhibited amplification of the neu gene. Four of these eleven patients died of disease an average of 16 months after diagnosis. The five patients without tumor amplification of the c-neu gene have been followed an average of 31.2 months without evidence of recurrent disease. Ten of fifteen tumor samples exhibited amplification of the c-myc gene. Five of the ten patients died of disease an average of 13.4 months after diagnosis. The remaining five patients have been followed for an average of 31.2 months and are free of disease. Six of the sixteen tumor specimens exhibited amplification of the both c-neu and c-myc genes, and four of these patients died of recurrent disease. Amplification of the c-neu or c-myc oncogene correlated with advanced-stage disease and poorly differentiated lesions, suggesting that oncogene amplification may predict biologically aggressive adenocarcinomas of the endometrium. PMID- 2227550 TI - Ovarian intraepithelial neoplasia demonstrated in patients with stage I ovarian carcinoma. AB - Retrospective review of sections of ovary from 50 patients with stage I, grade 1 3, epithelial ovarian carcinoma was performed to assess presence of cellular and nuclear atypia in noncancerous tissue adjacent to the primary tumor; ovarian tissue from 50 patients undergoing incidental oophorectomy was reviewed as well. Atypia was more common in cancer patients, and finding the combination of nuclear atypia, defined as presence of pleomorphism or irregular chromatin distribution, with cellular atypia, defined as presence of stratification or loss of polarity, allowed separation of cancer and control groups with 98% sensitivity and 100% specificity. Presence of nuclear and cellular atypia was used to define ovarian intraepithelial neoplasia (OIN). If OIN is demonstrated to precede ovarian carcinoma, then it may offer insights into the development of ovarian cancer and may eventually increase the feasibility of screening for this disease. PMID- 2227551 TI - Does serum CA-125 level prior to second-look laparotomy for invasive ovarian adenocarcinoma predict size of residual disease? AB - The records of 125 patients with nonmucinous invasive ovarian adenocarcinoma who underwent cytoreductive surgery, cisplatin-based combination chemotherapy, and second-look laparotomy were analyzed to correlate pre-second-look serum CA-125 levels with the size of residual ovarian cancer. The majority of patients with negative second-look laparotomy had normal serum CA-125 levels (46/50 or 92%). Of the 75 patients with positive second-look, 56 (75%) had normal CA-125 levels preoperatively. Twenty-three of twenty-four (96%) patients with residual disease less than or equal to 1 cm had normal CA-125 levels as did 20 of 28 (71%) patients with disease 1.1-2.0 cm. Although elevated serum CA-125 levels were invariably associated with visible/gross disease and increasing size of residual disease tended to be associated with increasing elevations of CA-125, normal CA 125 levels often occurred in the presence of large-volume (greater than 2 cm) disease (13/23, 57% of patients). The considerable overlap of serum CA-125 levels for all sizes of residual disease precluded precise prediction of residual disease size based on serum CA-125 level alone. PMID- 2227552 TI - Human immunodeficiency virus infection and cervical neoplasia. AB - To determine the relationship between human immunodeficiency virus (HIV) infection and cervical neoplasia, the characteristics of invasive and preinvasive cervical disease in 114 patients of known HIV status were assessed. Seven of thirty-seven patients (19%) under age 50 with invasive cervical carcinoma were HIV-positive, including a 16-year-old with stage IIIB disease. HIV-positive patients had more advanced invasive cancer than HIV-negative patients. Disease persisted or recurred in all HIV-positive patients compared to 37% of HIV negative patients. In HIV-positive patients, the median times to recurrence and death were 1 and 10 months, respectively. No HIV-positive patient had HIV-related symptoms. The mean T4:T8 cell ratio in HIV-positive patients was 0.49, compared to 1.86 in HIV-negative patients. The mean T4 cell count was 362/mm3 in HIV positive and 775/mm3 in HIV-negative patients. Colposcopic evaluations of the lower genital tract of 77 patients with abnormal smears revealed higher-grade cytology and histology in 25 HIV-positive than in 52 HIV-negative patients. HIV positive patients had significantly more multifocal/extensive lesions, multisite involvement, perianal involvement, evidence of human papillomavirus (HPV) infection, and associated gynecologic infections than HIV-negative patients. In areas at high risk for HIV infection, we must anticipate a high prevalence of HIV seropositivity in women with invasive cervical cancer. In the HIV-infected, cervical cancer is of advanced stage and responds poorly to therapy. Intraepithelial neoplasia in HIV-positive patients may be of higher grade than in HIV-negative patients, with more extensive involvement of the lower genital tract. PMID- 2227554 TI - Flow cytometric versus immunohistochemical analysis of ovarian cancer class I antigen expression: differences may represent a defect in antigen expression. AB - Class I antigen expression by ovarian epithelial neoplasms was determined by flow cytometric analysis and an immunoperoxidase technique for each specimen. The numbers of class I positive tumors determined by the methods were compared. The more subjective immunohistochemical analysis and the more objective flow cytometric technique revealed similar results as long as strict criteria for the interpretation of results was applied. Most of the tumor specimens revealed a homogeneous Gaussian distribution of green fluorescence, class I antigen expression, by flow cytometry. There were two specimens that exhibited a less than characteristic type of membrane staining. The antigen-antibody reaction product was expressed in the extracellular matrix, as well as on the cell membrane of certain cells. This may represent a defect in antigen expression and, if so, might alter the immune response to these tumors. PMID- 2227553 TI - Chemotherapy versus radiotherapy in the management of ovarian cancer patients with pathological complete response or minimal residual disease at second look. AB - The management of patients with epithelial ovarian cancer with no or minimal residual disease at second-look laparotomy after aggressive surgery and platinum based chemotherapy has not been definitively established. We report the results of a randomized study comparing three more courses of the same chemotherapy inducing the response (21 patients) with whole-abdomen radiotherapy (20 patients). Thirty-eight patients responded to first-line chemotherapy and three had stabilization of disease. In eight patients tumor debulking was performed at second-look laparotomy. No severe toxic effects were noted in both arms. Bowel obstruction occurred in one patient treated with radiotherapy. At a median follow up of 22 months, 11 of 20 patients in the radiotherapy arm and 6 of 21 in the chemotherapy arm progressed and 9 and 3 patients died, respectively. Although the number of randomized patients is small we stopped the trial because of the survival and progression-free survival advantage of chemotherapy-treated patients. PMID- 2227555 TI - Gynecologic radiotherapy fields defined by intraoperative measurements. AB - Whole-pelvis radiation therapy has been traditionally delivered through fields, the dimensions of which have been determined by convention and based largely on textbook anatomic landmarks. Since July 1986, 100 patients have had intraoperative retroperitoneal measurements carried out at the time of radical surgery in an effort to examine this anatomic basis for field dimensions. Structural measurements of the pelvic and paraaortic arterial branches were made in reference to the lumbosacral prominence to correlate with lymphatic pathways. The mean level of the aortic bifurcation was found to be 6.7 cm above the lumbosacral prominence. The mean level of the bifurcation of the common iliac artery was 1.7 cm above this reference point on the right and 1.4 cm above on the left. Both common iliac bifurcations were cephalad to the level of the lumbosacral prominence in 87% of patients. In only three patients were both bifurcations located below this level. Transverse pelvic dimension measurements demonstrated a width of 12.3 cm at the level of the obturator fossa and of 13.0 cm at the most inferior outside width of the external iliac arteries. To establish a simple external reference which could assist in defining radiotherapy field widths, the maximal separation of the femoral arteries at the level of inguinal ligaments was measured and averaged 14.6 cm. These data suggest that conventional fields frequently fail to correspond to true anatomic landmarks and that to optimally cover the lymphatics in radiotherapy, fields should, ideally, be based on intraoperative measurements. If such surgical guides are not available, we would suggest that standard whole-pelvis radiotherapy for cervical cancers should employ anterior and posterior fields with widths of at least 16 cm which will fully include the bifemoral separation. A superior border at the L4-L5 interspace is required to cover lymphatic pathways to the mid-common iliac nodal level. It may also be convincingly pointed out that the attachments of the uterosacral and cardinal ligaments are clearly posterior to the rectosigmoid, mandating lateral fields that should encompass the entire anterior sacral silhouette. PMID- 2227557 TI - Database management for a gynecologic oncology service. AB - With the ready availability of powerful desktop computers, the ability to manage large clinical databases has become practical. A computer can enhance the capability of a gynecologic oncology service to catalog, recall, and analyze data about patients, tumors, and therapies. While commercially available database packages can be used for this purpose, we have developed a custom database for tracking the clinical activity of a busy gynecologic oncology service. The system catalogs data about patients, admissions, tumors, and therapeutic modalities and uses this information to generate several useful reports. The reports are used for daily patient care, fellow and resident case statistics, and clinical research. What is unique about the system is that it is optimized for ease of use. The development of this tumor registry, its user friendliness, and advantages over a manual recordkeeping system are described. Unlike other tumor registries, our system is utilized on a daily basis for patient care. Therefore, the data being entered have an immediate usefulness in addition to being simultaneously added to the tumor register for retrospective clinical research. One may hypothesize that it would be useful if all gynecologic oncology services used a common computerized tumor registry that could allow for the sharing of information on a national or global scale. PMID- 2227556 TI - Clinical-pathologic study of stage IIB, III, and IVA carcinoma of the cervix: extended diagnostic evaluation for paraaortic node metastasis--a Gynecologic Oncology Group study. AB - Three hundred twenty patients were entered into GOG Protocol 63, a clinical pathologic study of stage IIB, III, and IVA cervical carcinoma. Following the completion of FIGO staging prerequisites, patients had computerized tomography (CT), a lymph-angiogram (LAG), and an ultrasound (US) of the aortic area. If any study was positive, a cytologic or histologic evaluation by fine-needle aspiration or selective paraaortic lymphadenectomy was performed. Paraaortic node dissection was mandated for patients with negative extended staging studies. Results of extended staging evaluations were compared with histologic or cytologic results. Two hundred sixty-four patients were eligible and evaluable. One hundred sixty-seven patients (63%) were stage IIB, 89 (34%) were stage III, and 8 (3%) were stage IVA. Positive paraaortic nodes occurred in 21% of stage IIB, 31% of stage III, and 13% of stage IVA. LAG sensitivity was 79% with a specificity of 73%. Sensitivity of CT and US was 34 and 19%, respectively, with specificities of 96 and 99%, respectively. The frequency of false-negative results with LAG for patients with stage IIB disease was 6%. This decrease is consistent with a stable sensitivity and specificity. These findings suggest that a negative LAG may be adequate to eliminate surgical staging in subgroups with low risk of metastasis to the aortic nodes. Until new noninvasive testing methods are developed, LAG appears to be the most reliable noninvasive examination to evaluate spread of cervical cancer to aortic nodes. PMID- 2227558 TI - Heterogeneity in hormone receptor status in primary and metastatic endometrial cancer. AB - The rationale for endocrine therapy in patients with advanced endometrial carcinoma may be based on the presence of estrogen or progesterone receptors in the primary tumor. A study was designed to evaluate tumor cell heterogeneity of steroid hormone receptors in the primary and metastatic sites in endometrial cancer. Primary endometrial cancer tissue samples from 10 patients and 16 metastatic tumor sites were simultaneously analyzed for estrogen and progesterone receptors, using a radioligand biochemical assay. The primary tumor was estrogen receptor (ER) and progesterone receptor (PR) positive in 70 and 60% of the patients, respectively. The metastatic sites were ER positive in 63% and PR positive in 25%. The primary tumor tissue and the metastatic disease showed an identical ER and PR status in only 25 and 19%, respectively. Four patients had multiple metastatic sites analyzed. In two of four patients the PR values, and in three of four patients the ER values, in these metastatic sites were discordant. These data support the concept of tumor cell heterogeneity for steroid hormone receptors in endometrial cancer. To optimize treatment planning, it may be important to biopsy primary, metastatic, and recurrent tumor sites for individual analysis of receptor activity. PMID- 2227559 TI - Bone marrow involvement in epithelial ovarian cancer by immunocytochemical assessment. AB - The incidence of bone marrow involvement with epithelial ovarian cancer has been evaluated as a continuation of interest in autologous bone marrow support. Fifty eight aspirates were obtained on 50 patients and 53 aspirates were evaluable. Immunocytochemistry with the monoclonal cytokeratin antibodies 35 beta H11 and 34 beta E12 was performed. There have been no complications. Twelve (23%) were positive and three were indeterminate. Stage, grade, and CA-125 level were not different in the two groups. No patient had a positive biopsy at the time of initial diagnosis. The majority of patients were drawn from second-look procedures; of these, 7 of 19 were positive. Five of twelve with positive aspirates died from disease versus 5 of 38 with negative aspirates, and patients with a positive aspirate had a longer overall survival time until death from disease. We can confirm the presence of epithelial ovarian cancer in 23% of patients at varying times in the course of their disease. We cannot identify risk factors for the development of this finding nor the viability of those cells when found in this data set. PMID- 2227560 TI - Concurrent chemoradiation in advanced cervical cancer. AB - The pelvis is the predominant site of failure following radical radiotherapy (RT) for locally advanced cervical cancer. We report the results of phase I-II studies on 200 patients with bulky (greater than or equal to 5 cm) carcinoma of the cervix. Patients were treated between 1981 and 1988 on sequential protocols of concurrent chemoradiation to establish an acceptable treatment regimen. RT with daily or partially hyperfractionated pelvic (n = 154) or pelvic plus paraaortic (n = 46) fields was given by continuous (n = 154) or split course (n = 46) regimens. Infusional fluorouracil (5-FU) in a dose of 1 g/m2/day was given on the first and last 4 days of a 5-week course of continuous RT, or with both halves of split course RT. Seventy-eight patients received bolus mitomycin C (Mit-C), 6 mg/m2, once or twice with the start of the 5-FU infusion. The median external RT dose was 46 Gy (range 40 to 65 Gy) followed in 90% (n = 181) by a single intracavitary application of 40 Gy using a linear source of cesium-137. Median follow up is 2.5 years (range 0.6 to 6.9 years) and is sufficient to reliably estimate late toxicities. Acute toxicities were transient oral mucositis (13), RT interruption for enteritis (7), febrile neutropenia (3), and thrombocytopenic tumor bleed (1). Serious late toxicities resulted in death in 3 patients and occurred in bladder in 6 and in bowel in 25, including 8 patients with tumor recurrence. The incidence of late bowel toxicity correlated with the specific therapy given and decreased with each successive protocol. On logistic regression the only treatment variable showing a statistically significant effect on complications was the use of Mit-C (P = 0.0053). Pelvic RT and 5-FU alone produced fewer complications, only 4/105, than historically seen with standard pelvic RT alone. Three-year pelvic control and survival rates were 85 and 71% respectively in stage Ib/II (n = 100) and 50 and 42% in stage III/IV (n = 100). Encouraged by these results and decreased toxicity, we have begun a phase III study to determine whether the addition of concurrent 5-FU to continuous partially hyperfractionated pelvic RT improves local control and survival. PMID- 2227561 TI - Class I histocompatibility antigen expression: a prognostic factor for aneuploid ovarian cancers. AB - Epithelial ovarian cancers with aneuploid DNA content are associated with a poorer clinical course than diploid tumors. Flow cytometric analysis may further categorize aneuploid tumors based on the relative expression of cell surface histocompatibility (HLA) antigens. Surgical specimens from 20 patients with aneuploid tumors were stained using an indirect immunofluorescence method with primary murine monoclonal antibodies W36/22 (class I HLA surface antigens) and L5.1 (irrelevant antibody), counterstained with propidium iodide (DNA stain), and analyzed with the flow cytometer using a computer program to correct staining intensity for cell size. Patients with high or low class I expression were similar with respect to age, stage, histology, grade, and residual disease following surgical debulking; all patients were treated with cisplatin-based chemotherapy. Women with low class I HLA antigen expression had higher progression rates and death rates than patients with high class I HLA expression. Low class I HLA antigen expression is a poor prognostic factor among patients with aneuploid ovarian cancers. PMID- 2227562 TI - Pelvic exenteration with low rectal anastomosis: survival, complications, and prognostic factors. AB - Between July 1979 and January 1989 there were 31 patients who underwent pelvic exenteration with low rectal anastomosis (PE and LRA) at the University of Alabama at Birmingham (UAB). There were no operative deaths; however, 32% of the patients experienced significant postoperative morbidity. Survival (Kaplan-Meier) at 1 year is 86%. Overall survival is 68% with follow-up ranging from 10 months to greater than 9 years. For those patients with disease confined to the cervix and/or vagina (n = 18) the survival is 89% while it is 38% for patients with spread to the bladder, rectum, or parametrium (n = 13). Survival was not influenced by tumor differentiation, time from irradiation to exenteration, or initial stage. Complete healing of the LRA was achieved in 16 patients (52%). However, in the subset of patients with an omental wrap (n = 13) the complete healing rate is 85%. Protective colostomies were utilized in 12 patients; however, this was not shown to improve the healing rate of the LRA. This group of patients is compared to similar patients who had anterior pelvic exenteration at UAB for morbidity and survival. LRA at the time of pelvic exenteration for recurrent cervical cancer is associated with acceptable morbidity and survival and should be attempted in those patients who are appropriate candidates. PMID- 2227563 TI - Radioimmunoscintigraphy of ovarian tumors using a new monoclonal antibody, SM-3. AB - Radioimmunoscintigraphy with SM-3 monoclonal antibody produces results similar to those obtained with 123I-labeled HMFG-2. The tumor specificity of SM-3 in vitro is not as marked as that in vivo. SM-3 is, however, much easier to produce in tissue culture and, with the availability of 99mTc labelling, has allowed radioimmunoscintigraphy to be done as an outpatient procedure. This technique has important implications for the continuing management of patients with ovarian cancer. PMID- 2227564 TI - Chromosome abnormalities in human epithelial ovarian malignancies. AB - Karyotypic analysis of tumor specimens from 29 patients with untreated epithelial ovarian carcinoma was performed at the University of Kentucky Medical Center. Twenty-three of the twenty-nine tumors had adequate cells for analysis. Seventeen of these tumors exhibited chromosome abnormalities. Chromosome alterations were complex, with an average of seven different abnormal chromosomal patterns per tumor (range 2-14). Chromosomes 1 and 11 were the most commonly involved, being abnormal in 89 and 83% of tumors, respectively. Chromosomes 3 and 7 were also frequently abnormal. In contrast to invasive tumors, alterations in chromosomes 1 and 11 were not seen in the two tumors of borderline malignant potential. Evidence for DNA amplification of IGF2, Ha-ras-1, and c-ets was not observed. Amplification of the c-erbB-2 oncogene was present in two tumors. These findings indicate that multiple karyotypic abnormalities occur in untreated epithelial ovarian malignancies, with chromosomes 1 and 11 being the most frequently abnormal. These data also suggest that alterations of these chromosomes may be associated with the biologically aggressive behavior of frankly invasive ovarian tumors. PMID- 2227565 TI - Estimates of dose to intraperitoneal micrometastases from alpha and beta emitters in radioimmunotherapy. AB - Intraperitoneal metastases from ovarian and other gynecologic tumors are a significant source of treatment failure. In recent years, investigators have used radiolabeled monoclonal antibodies to treat this disease with encouraging results. We have developed a dose calculational technique which generates isodose distributions from intraperitoneally administered alpha and beta particle emitters. In this study we apply the calculations to tissue biopsy samples to determine the adequacy of dose to ovarian micrometastases. Tissue samples from staging biopsies at the time of surgical debulking are scanned to identify small metastases. The patient population studied comprised those with ovarian disease who based on clinical criteria would be considered good candidates for intraperitoneal radioimmunotherapy. The regions of interest (which include the tumor and surface of the peritoneum) are digitized and tumor volumes are contoured. Dose calculations based on the modeling of intraperitoneally administered antibodies radiolabeled with various isotopes is performed and the minimum dose to tumor and normal tissue is assessed. For example, with tumor uptake of 0.1% injected dose per gram of tissue, the surface tumor dose from alpha emitters is up to 45,000 rads. The dose falls to 6000 rads at approximately 40 microns from the peritoneal surface. The surface dose from 20 mCi 90Y administered in 1500 ml saline is up to 10,000 rads, and at a 2-mm depth, approximately 2000 rads. From our calculation dose distribution from radioimmunotherapy varies as a function of physical characteristics of the isotope, absorption of activity, and amount of disease being treated. PMID- 2227566 TI - Tumor markers in gynecologic oncology. PMID- 2227567 TI - Debridement of vaginal radiation ulcers using the surgical Ultrasonic Aspirator. AB - The surgical Ultrasonic Aspirator (USA) is a fairly new surgical instrument used for an increasingly wide range of procedures. This paper introduces a new application: debridement of vulvovaginal necrotic ulcers resulting from intracavitary radiation therapy. The ultrasonic aspirator allowed removal of the soft, necrotic tissue while preserving underlying healthy, firm tissue and blood vessels. PMID- 2227568 TI - Usefulness of endocervical curettage (ECC) PMID- 2227569 TI - Pretreatment serum levels of CA-125, carcinoembryonic antigen, tissue polypeptide antigen, and placental alkaline phosphatase, in patients with ovarian carcinoma, borderline tumors, or benign adnexal masses: relevance for differential diagnosis. AB - Pretreatment serum levels of the antigens CA-125, tissue polypeptide Antigen (TPA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) were determined in samples from 295 women with adnexal masses. At laparotomy 48% of patients had epithelial ovarian carcinoma, 9% had tumors of low malignant potential, and 8% suffered from malignancies of other kinds. The sensitivity of CA-125 with 35 U/ml as the cutoff was 88% in women with ovarian carcinoma, but 74% among those with limited disease and 58% in borderline malignancy. Only 6 of 17 mucinous ovarian carcinomas were detected. Specificity was 83%. CEA was elevated above 5.0 micrograms/liter in 15 of 17 patients with mucinous ovarian cancer. TPA detected advanced stages of malignancy, but the sensitivity was low, 53%, in cases with limited disease. PLAP was elevated in 46% of ovarian carcinoma patients. For detecting malignancy overall, the use of a parallel combination of the CA-125 and CEA assays was more sensitive than use of CA-125 as a single marker. This test combination may be of value in the diagnosis of adnexal masses. The predictive value of a positive result was 90%, and that of a negative result, 76%. PMID- 2227570 TI - Pretreatment serum levels of CA-125, carcinoembryonic antigen, tissue polypeptide antigen, and placental alkaline phosphatase in patients with ovarian carcinoma: influence of histological type, grade of differentiation, and clinical stage of disease. AB - Pretreatment serum levels of the tumor-associated antigens CA-125, tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) were analyzed in 142 patients with epithelial ovarian carcinoma, and related to clinical and histopathological parameters. In a linear multiple regression model CA-125 serum levels were profoundly influenced by the type of tumor, i.e., mucinous or nonmucinous. Clinical stage also had significant impact, whereas grade of differentiation did not, when the other two factors were taken into account. CEA levels were also dependent mainly on histological type. Mucinous tumor cases had high levels. Only clinical stage or tumor burden had a significant impact on TPA levels. PLAP levels were significantly influenced by histological type of tumor and by grade of differentiation but not by clinical stage. The dependence of CA-125 levels upon clinical stage was evident only in nonmucinous tumors. Furthermore, size of the primary tumor was not important for the CA-125 value, in contrast to FIGO stage. Thus CA-125 is primarily a sensitive indicator of disseminated disease in ovarian carcinoma patients. On the basis of the CA-125 level it was possible to predict the extent of disease with an overall accuracy of 55%. If TPA and CEA levels were also considered, the predictive accuracy was 63%. PMID- 2227571 TI - Epidemiology of adenocarcinoma of the cervix. AB - There is general evidence that the incidence of adenocarcinoma of the cervix has been rising, particularly among younger women. The determinants of these trends, however, remain largely unknown. We have reviewed the epidemiology of adenocarcinoma of the cervix using descriptive data from cancer registration and clinical series and two main sources of analytical data: clinical studies comparing cervical adenocarcinoma (AC) and squamous carcinoma (SC) and formal case-control and cohort epidemiological studies. In both the United States and northern Europe there is evidence of the rising frequency of AC in absolute and relative terms as compared to SC. These trends are generally restricted to younger women: under-age-35 AC incidence approximately doubled from the early 1970s to the early 1980s. Available data, although scanty, consistently show that the frequency of cervical adenocarcinoma rises with the number of partners and with decreasing age at first intercourse, suggesting a potential role for sexually transmitted (viral) factors. In clinical series, nulliparity was reported more frequently in AC than in SC cases but an inconsistent association was found in three formal epidemiological studies. Similarities with the epidemiology of endometrial cancer are also suggested from the association with overweight, while a possible relation with hypertension and diabetes is based on clinical series only and hence more difficult to interpret. Thus, adenocarcinoma of the cervix appears to share epidemiological characteristics with both adenosquamous cancer of the cervix and adenocarcinoma of the endometrium, although uncertainties in classification and registration leave several questions unanswered. PMID- 2227572 TI - Radiation therapy in stage III ovarian cancer following surgery and chemotherapy: prognostic factors, patterns of relapse, and toxicity: a preliminary report. AB - Twenty patients with FIGO stage III epithelial ovarian cancer who had undergone maximum cytoreductive surgery (including pelvic and paraaortic lymph node dissection) and combination chemotherapy (4-10 cycles, median 6) were treated with irradiation to the abdomen and pelvis with 30 Gy followed by diaphragmatic/paraaortic and pelvis boost fields to 42 and 51.6 Gy, respectively. Second-look laparotomy was not performed. Seventeen of 20 patients completed the planned course of radiation. In 2 cases, failure to complete treatment was related to acute hematologic toxicity, and 1 patient refused further treatment. Five patients (29%) required treatment breaks ranging from 8 to 16 days (median, 12 days) due to pancytopenia. Actuarial overall survival and relapse-free survival at 3 years for the 17 patients who completed radiation was 69 and 47%, respectively, with follow-up ranging from 19 to 53 months (median: 24, mean: 27.6 months). Seven patients (41%) relapsed within the abdomen alone and 2 patients developed extraabdominal lymph node metastasis as their sole site of failure. The prognostic factors evaluated for correlation with relapse-free survival included histologic subtype, grade, amount of residual disease at the time of surgery, and nodal involvement; only residual tumor at surgery (none vs less than or equal to 2 cm or greater than 2 cm) was found to be statistically significant (P less than 0.01). Three-year overall survival correlated with amount of residual disease following the initial cytoreductive surgery. It was 100% for patients with no residual disease, 66.7% for less than or equal to 2 cm, and 26.7% for those with greater than 2 cm residual disease, respectively. Radiation treatment was well tolerated, with only one patient developing treatment-related bowel obstruction 7 months after radiation therapy. The results of this planned trimodality treatment approach compare favorably with those reported following surgery and chemotherapy, particularly in patients who have been maximally cytoreduced. PMID- 2227573 TI - Human ovarian cancers specifically bind daunorubicin-OC-125 conjugate: an immunofluorescence study. AB - This study was designed to test the specific binding to human ovarian serous adenocarcinomas of a drug-antibody conjugate [daunorubicin (DNR-OC-125], made from a new analog (PIPP-DNR) of daunorubicin that chemically links the drug to monoclonal antibodies. We recently reported that the DNR-OC-125 conjugate is selectively toxic in vitro to dividing cell populations of the human ovarian cancer cell lines SK-OV-3 and OVCAR-3 that express the CA-125 antigen [F. Sweet, L. O. Rosik, G. M. Sommers, and J. L. Collins, Gynecol. Oncol. 34, 305-311 (1989)]. In the present study, immunofluorescence data show that the DNR-OC-125 conjugate has high affinity and specificity for proliferating malignant cells from human ovarian tumors. The results demonstrate that the DNR-OC-125 conjugate retains the specific binding to CA-125 antigenic sites characteristic of the OC 125 monoclonal antibody moiety. The DNR-OC-125 conjugate selectively binds to CA 125 antigen-positive ovarian cancerous tissue in both cryostat and paraffin embedded tissue sections. This is consistent with the earlier in vitro data from dividing populations of two human ovarian cancer cell lines that revealed retention by the DNR-OC-125 conjugate of both the specificity due to OC-125 and the cytotoxicity of daunorubicin. The present immunofluorescence studies in the DNR-OC-125 conjugate is tested on human ovarian serous tumors indicate that the OC-125 monoclonal antibody can indeed serve as a cancer-targeting carrier for daunorubicin and its analogs. PMID- 2227574 TI - Recurrent carcinoma of the vulva after conservative treatment for "microinvasive" disease. AB - Although the standard therapy of vulvar carcinoma remains radical surgery, this approach is accompanied by significant postoperative morbidity and psychological adjustment. Radical hemi-vulvectomy and ipsilateral superficial groin node dissection are increasingly used for patients with "early" or "microinvasive" disease. Two patients with an "early" vulvar carcinoma were treated conservatively and later developed recurrent disease. Despite further surgery and radiotherapy, both patients eventually died of disease. The case histories are described and the pertinent literature is discussed. PMID- 2227575 TI - Interobserver variation in ovarian measurements using transvaginal sonography. AB - Ultrasound examination of ovarian size and morphology has been proposed as a screening method for ovarian carcinoma. A screening test must give consistent results when performed by different examiners to reliably determine the sensitivity and specificity of the test. This study was designed to evaluate interobserver variation in ovarian size measurements using transvaginal sonography. Two examiners independently measured 86 ovaries in three planes and ovarian volumes were calculated using the prolate ellipsoid formula. The correlation coefficient between the ovarian volume measurements made by each examiner was 0.960. These results indicate that interobserver variation in ovarian volume measurements is extremely low as determined by transvaginal sonography. PMID- 2227576 TI - Study of the selective cytotoxic properties of cationic, lipophilic mitochondrial specific compounds in gynecologic malignancies. AB - Cationic lipophilic compounds have a unique cytotoxic mechanism of action which is dependent on mitochondrial-specific localization of these fluorescent dyes. We have demonstrated in vitro that carcinoma cells, which have a higher negative mitochondrial membrane potential than normal cells, have an increased accumulation and retention of two of these compounds. The compounds tested were rhodamine 123 and dequalinium (DECA). After the development of a reproducible murine intraperitoneal (ip) human ovarian cancer model, which maintained the biologic characteristics of the parent cell line, we undertook in vivo evaluation of DECA. Mice with intraperitoneal tumor inoculations were treated with cisplatin, and/or DECA. When compared to cisplatin, a chemotherapeutic agent known to be effective in the treatment of clinical ovarian cancer, DECA was significantly more efficacious and seemed less toxic in the murine model. Cisplatin and DECA used together were possibly synergistic. Cationic lipophilic compounds may prove to be an exciting new class of antineoplastic agents which exploit intracellular, mitochondrial differences between normal cells and cancer cells. PMID- 2227577 TI - Is radical hysterectomy always necessary in early cervical cancer? AB - A semiquantitative histopathologic grading system was used in combination with flow cytometric measurements of tumor cell DNA content to predict the risk of lymph node metastases in early cervical cancer. A retrospective study of 126 stage IB patients showed that a group with no risk of lymph node involvement could be identified by the use of both the histopathologic score and the DNA index. The results were confirmed in a prospective investigation of 59 new patients. Simple hysterectomy may be advised in low-risk patients. PMID- 2227578 TI - Serous carcinoma of the ovary: value of computed tomography in detection of calcified pleural and pulmonary metastatic implants. AB - Reported are three cases of serous papillary cystoadenocarcinoma of the ovary with pleural and pulmonary calcified metastatic implants detected by computed tomography (CT), but not by chest X-ray. CT patterns of metastatic calcifications were considered because of the unexpected frequency of this finding (15.7%) and in view of a possible clinical use of CT in monitoring extraabdominal disease. PMID- 2227579 TI - Gallstone ileus masquerading as recurrent carcinoma of the ovary. AB - A case of gallstone ileus in a patient with carcinoma of the ovary is presented. A 78-year-old female with stage III carcinoma of the ovary underwent optimal debulking surgery followed by six courses of chemotherapy and a microscopically positive second-look laparotomy. She was treated by whole-abdomen pelvic radiation. She then developed progressive nausea, vomiting, abdominal distension, and eventually complete small bowel obstruction. The diagnosis of gallstone ileus was made preoperatively based on the radiological findings. The pathophysiology of gallstone ileus is discussed in the differential diagnosis of patients treated for carcinoma of the ovary. PMID- 2227580 TI - Advanced vulvar carcinoma treated with internal iliac arterial embolization therapy after radiotherapy. AB - Two patients with vulvar carcinoma are reported who were treated with internal iliac transcatheter arterial embolization and radiotherapy. Patient 1 had T3N3M0 vulvar carcinoma. The lesion remaining after radiotherapy was treated by bilateral internal iliac arterial embolization. Vulvectomy was then performed, and the resected specimen showed no residual malignant cells. This patient is alive without recurrence 4 years 7 months after operation. Patient 2 (T3N0M0 vulvar carcinoma) underwent radiotherapy, and the remaining malignant tumor disappeared after bilateral internal iliac artery embolization. This patient has remained disease free without vulvectomy for 3 years after treatment. PMID- 2227581 TI - Breast carcinoma metastatic to endometrial polyp. AB - An elderly woman presented with an enlarged uterus without uterine bleeding. The hysterectomy specimen contained a large, solitary intrauterine mass. Microscopic examination revealed metastatic poorly differentiated adenocarcinoma infiltrating an endometrial polyp. This metastatic tumor appeared histologically identical to the patient's ductal carcinoma of the breast removed by modified radical mastectomy 6 years earlier. An extrapelvic primary carcinoma metastatic to tan endometrial polyp is a very rare event but should be included in the differential diagnosis of endometrial carcinomas. PMID- 2227582 TI - Bone metastasis from gynecologic carcinomas: a clinicopathologic study. AB - Between 1948 and 1984, autopsies were performed on 305 patients with primary carcinomas of the cervix, endometrium, ovaries, fallopian tubes, vulva, and vagina. Skeletal metastases were detected premortem and at autopsy in 49 cases (16.1%): cervix, 20 (40.8%); endometrium, 17 (34.7%); ovary, 7 (14.3%); vulva, 4 (8.2%); fallopian tube, 1 (2%). There were no cases of osseous metastasis from vaginal carcinoma. The incidence and sites of metastasis from these gynecologic carcinomas were correlated with their clinical and histopathologic classifications. This clinicopathologic study, based on autopsy data, demonstrates that osseous metastases are not uncommon, are significantly greater than clinically appreciated, and correlate with advanced anatomic stage and histopathologic type and grade. PMID- 2227583 TI - Electrosurgical debulking of ovarian cancer: a new technique using the argon beam coagulator. AB - Survival of ovarian adenocarcinoma patients depends on the size of the largest residual nodule at the end of debulking surgery. The argon beam coagulator (ABC) delivers radiofrequency current traveling in a beam of argon gas which facilitates tumor destruction and hemostasis. We used the ABC as an aid to cytoreduction in seven consecutive patients with stage III/IV ovarian cancer. Despite extensive disease, optimal debulking was achieved in all seven patients: four (57%) had no gross residual cancer; three had residual nodules of 2-3 mm. The ABC facilitated tumor destruction on the diaphragm, bowel wall and mesentery, presacral space, ureters, vagina, and iliac vessels. In addition, the ABC was used to "sterilize" surgical margins such as the vaginal cuff and rectosigmoid colon anastomoses. Five patients are currently alive, four disease free, with mean survival of 33 months since diagnosis. The ABC enables debulking of ovarian cancer in sites inaccessible to conventional resection. PMID- 2227584 TI - Etoposide combination chemotherapy in refractory ovarian malignant germ cell tumor. AB - Thirty-three patients with malignant germ cell tumor of the ovary received postoperative vincristine, dactinomycin, and cyclosphosphamide (VAC) treatment. Eight failed VAC treatment and received etoposide, bleomycin, and cisplatin (PEB) combination chemotherapy. Three were cured and remained disease free 24-79 months after completion of PEB therapy. PMID- 2227585 TI - Influence of histological features and treatment on the prognosis of patients with cervical cancer metastatic to pelvic lymph nodes. AB - Ninety-seven patients with stage IB through IIB cervical cancer metastatic to pelvic lymph nodes treated at Magee-Womens Hospital, Pittsburgh, Pennsylvania, between 1955 and 1979 were analyzed retrospectively to determine histological factors which might predict treatment failure. All patients were treated by radical hysterectomy with a pelvic lymphadenectomy (S) or in combination with radiation therapy (S + RT) (27 and 73%, respectively) and were followed for a minimum of 5 years or until death. There were no significant differences between the two treatment groups when compared for patient age at diagnosis, distribution of disease stages, cell type, and tumor differentiation. The groups were dissimilar only with respect to the number of lymph nodes found to contain metastatic carcinoma. Significantly more patients treated by S + RT than by S alone were found to have metastasis to more than one node. Of patients treated with S alone, 65% recurred within 5 years compared with 51% with the addition of RT (P less than 0.16). The extent of both lymphocytic and polymorphonuclear infiltration of the tumor did not influence the probability of recurrence following treatment; however, tumors with a marked eosinophilic infiltration recurred significantly more frequently than those without (P less than 0.05). PMID- 2227586 TI - Clinical significance of hyperkeratosis and parakeratosis in otherwise negative Papanicolaou smears. AB - To ascertain the clinical significance of hyperkeratosis and parakeratosis in otherwise negative Papanicolaou smears, we retrospectively reviewed 96 patients with these findings seen during a 32-month period. Evaluation included repeating the smear and performing colposcopy in all patients. Colposcopically directed biopsy and endocervical curettage were performed when appropriate. Only one patient had human papillomavirus (HPV) infection. The isolated finding of hyperkeratosis or parakeratosis was not associated with an increased incidence of cervical intraepithelial neoplasia or HPV and, clinically, was not associated with uterine descensus or vaginal prolapse. PMID- 2227587 TI - Occult pleural involvement in stage III ovarian carcinoma: role of diaphragm resection. AB - In a 2-year period 12 diaphragmatic resections were performed on 11 patients with invasive metastases from ovarian carcinoma without significant complications, via transabdominal approach in 10 instances and thoracoabdominal incision in 1. Full thickness penetration of the diaphragm by tumor occurred in all instances without prior evidence of pleural involvement (occult Stage IV). Six patients had primary disease (Group A) and 5 had recurrent disease (Group B). Ten patients who underwent excision of nonpenetrating diaphragmatic metastases were analyzed for comparison (Group C). Mean diameters of the metastases were as follows: Group A, 7.84 +/- 1.60 cm; Group B, 7.00 +/- 2.24 cm; Group C, 2.51 +/- 1.08 cm. The difference in mean diameter between the penetrating (Groups A and B) and nonpenetrating (Group C) tumors was highly significant (P less than 0.01). Penetrating tumors were 5.0 cm or greater; nonpenetrating tumors were 4.0 cm or less. Invasiveness of diaphragmatic metastases was inversely related to survival in patients with primary but not recurrent disease. Group A patients had a marked survival disadvantage (median survival time of 8 months; range 7-25 months) compared to Group C (median survival time of 26 months; range 13-96+ months; P less than .05). In contrast, Group B patients appeared to gain salutory palliation despite large diaphragmatic masses involving the pleural surface (4/5 alive at 16(+)-33+ months following surgery). Previous reports of response and survival in patients with Stage III Ovarian cancer may have included patients with "occult Stage IV" disease. PMID- 2227588 TI - Crossover study with cisplatin or carboplatin in advanced ovarian cancer. AB - Fifty-seven patients who had progressed during or relapsed after randomized first line combination chemotherapy containing cisplatin or carboplatin were entered into a crossover study in which the analog not previously assigned was administered alone as salvage treatment. Carboplatin and cisplatin were administered at doses of 400 and 100 mg/m2, respectively, every 28 days. Among the 24 patients enrolled in the cisplatin arm, 6 (25%) objective responses (ORs) (3 complete, 3 partial) were observed, whereas 3 partial responses were obtained in the 33 carboplatin-treated patient (9%). Analysis of results, according to response to first-line chemotherapy, demonstrated that the patients who progressed were sensitive only to cisplatin second-line treatment (OR: 3/12), with no responders among carboplatin-treated patients (OR: 0/11). All patients were treated on an outpatient basis and therapy-related toxic effects were mild, consisting chiefly of myelosuppression, and more frequent in the carboplatin group. In our opinion, carboplatin 400 mg/m2 per cycle is scarcely effective in patients with refractory or relapsed ovarian cancer pretreated with cisplatin regimens, whereas cisplatin 100 mg/m2 per cycle appears to be an effective salvage therapy even in patients not responding to carboplatin. The dose of carboplatin should be further escalated especially in refractory patients. PMID- 2227589 TI - The impact of whole-abdomen radiotherapy on survival in advanced ovarian cancer patients with minimal residual disease after chemotherapy. AB - Between March 1982 and March 1987, 26 patients with minimal residual epithelial ovarian cancer after cisplatin-based chemotherapy were treated with whole-abdomen irradiation [moving-strip technique (MST)] with or without pelvic boost. Prior to radiation residual disease was macroscopic (less than or equal to 0.5 cm) in 8 cases and microscopic (positive random biopsies) in 18 cases (8 diffuse, 10 localized). Eighty percent of patients completed the planned therapy, 34% with interruptions secondary to hematologic or gastrointestinal toxicity. With a median follow-up time from completion of radiotherapy of 24 months, 34.6% of patients remain alive. The 3-year survival rates (from the second-look procedure) are 50% for the patients with microscopic tumor and 25% for those with macroscopic residual disease. Progression-free intervals are statistically different in the two groups: 16.9 months for microscopic residuals and 6.16 months for macroscopic tumors (P = 0.037). All but two of the recurrences were in the irradiated field (pelvis and/or abdomen); one was distant (pleural) and one only retroperitoneal. Small bowel injury was the most limiting complication: 3.8% was registered as fatal acute enteritis and 19% as late obstruction or malabsorption syndrome, necessitating surgical intervention in 10% of treated cases. PMID- 2227590 TI - Studies on the distribution of abnormal cells in cytological smears. VII. Cervical brush versus plastic and wooden spatulas. AB - A model system of exfoliated normal human cervicovaginal squamous cells, exfoliated rodent tumor cells, and acellular, viscous, mucuslike material was used to investigate cell deposition on smear preparations made with three different instruments: plastic spatulas, wooden spatulas, and brush-tipped collectors. The total number of exfoliated cells and the total number of tumor cells present within the randomly distributed holes were then recorded for 41 smear preparations. For smears done with the brush, a total of 47,146 exfoliated cells were recorded; with wooden spatulas, 4517 cells; and with plastic spatulas, 7648 cells. When the brush was used, 6905 tumor cells were recorded. When wooden or plastic spatulas were applied, 563 and 1132 tumor cells were found, respectively. Thus, the brush yielded 12.2 and 6.1 times more tumor cells than plastic and wooden spatulas, respectively. PMID- 2227591 TI - Surgical complications of obese patients with endometrial carcinoma. AB - Sixty-seven patients had exploratory laparotomy for stage I and II (occult) adenocarcinoma of the endometrium. Acute surgical complications were analyzed in obese and in normal-weight patients. Compared to normal-weight patients, obese patients had significantly higher rates of wound infection and wound dehiscence, longer operating time, greater blood loss, and longer hospital stay. Wound infection and wound dehiscence were significantly related to postoperative anemia. PMID- 2227592 TI - Prognostic significance of single versus multiple lymph node metastases in cervical carcinoma stage IB. AB - From January 1, 1970, to December 31, 1985, 51 patients with stage IB (FIGO) carcinoma of the cervix with lymph node metastases were treated at the University Hospital, Groningen, The Netherlands. The survival rate was 54% and the average duration of follow-up was 78 months (range 47-132). Important clinical variables for survival were investigated retrospectively: the survival rate in patients with a single lymph node metastasis (with tumor confined to the node itself) (n = 23) appeared to be much better than that of patients with multiple node involvement and/or single nodes with extranodular tumor infiltration (n = 28); survival was 85 and 24%, respectively (P less than 0.001). The same applied to patients with only occult lymph node involvement: the survival rate in patients with occult involvement of the hypogastric, external iliac, or obturator nodes was 87% in 19 patients with a single metastasis and 53% in 15 patients with multiple node involvement (P less than 0.02). The survival rate in 8 patients with adenomatous histological components was 42%. In 42 patients with squamous cell carcinoma, the survival rate was 56%. This difference was not statistically significant. Treatment complications and the effect of treatment on the site of recurrence were investigated. PMID- 2227593 TI - DNA ploidy level as prognostic factor in low stage carcinoma of the uterine cervix. AB - Flow cytometry was used to measure DNA content of tumor cells in paraffin embedded archival material from 89 patients with squamous cell carcinoma of the cervix uteri stages IB and IIA. Patients were all treated with radical hysterectomy and transperitoneal lymphadenectomy. Twenty-four percent received radiotherapy postoperatively because of tumor spread into parametria or positive lymph nodes. Ploidy grade was compared to other prognostic factors. DNA aneuploidy was seen in 44 (49%), DNA-diploidy in 16 (18%) and 29 (33%) of the tumors were DNA-periploid. Sixty-nine (78%) patients were in FIGO stage IB, 20 (22%) in IIA. In 19 (21%) lymph node metastases were found, vasoinvasion in 25 (28%). Overall disease-specific 5-year survival was 80%. There was a significant effect of positive lymph nodes (90% vs 47%) and vasoinvasion (87% vs 64%) on the 5-year survival (resp. P less than 0.01 and P = 0.02). No correlation was found between stage (81% for IB vs 80% for IIA) or DNA-ploidy grade (81% for aneuploidy, 82% for periploidy, 79% for diploidy) and survival (resp. P = 0.9 and P = 0.8). Ploidy grade was equally divided over other prognostic factors. In stepwise Cox regression analysis DNA-ploidy grade showed no independent effect on survival. We conclude that DNA flow cytometry in this material was of no additional prognostic value. PMID- 2227595 TI - Epithelial ovarian tumors of borderline malignancy. AB - Between January 1975 and January 1987, 80 patients underwent primary surgery at Brigham and Women's Hospital for epithelial ovarian tumors of borderline malignancy. Surgical staging revealed 52 (65%) patients with stage IA, 2 (2.5%) with stage IB, 10 (12.5%) with stage IC, 4 (5%) with stage II, 11 (13.8%) with stage III, and 1 (1.2%) with stage IV. All 37 patients with mucinous tumors had stage I disease, whereas 13 (33%) of 39 patients with serous tumors had stage II IV disease. The mean sizes of mucinous and serous ovarian tumors were 18.7 and 10 cm, respectively. At initial surgery, 48 (60%) patients had a total abdominal hysterectomy with bilateral salpingo-oophorectomy and 16 (20%) had an oophorectomy. Sixteen (20%) patients underwent cystectomy, 6 (37.5%) of whom subsequently had an oophorectomy. All 10 patients treated by cystectomy alone have remained disease free. CA-125 levels were normal in 5 patients with stage I disease, but were elevated in 6 of 8 patients with more advanced tumors. Current disease status was determined in 72 patients (90%); 69 (95.8%) are alive and disease free, 1 (1.4%) patient is alive with tumor, and 2 (2.8%) patients died, free of disease. PMID- 2227596 TI - Restorative effects of calmodulin antagonists on reduced cisplatin uptake by cisplatin-resistant human ovarian cancer cells. AB - In the present study, we attempted to determine effects of calmodulin antagonists (W-7 and W-5) on cisplatin uptake by human ovarian cancer cells, using KF cells derived from serous cystadenocarcinoma of the ovary and cisplatin-resistant cells (KFr). The degree of cisplatin resistance of the KFr cells was about 3.7-fold higher than that of the parent KF cells, with regard to the concentration of cisplatin required for 50% inhibition of cell proliferation (IC50). When KF and KFr cells were incubated with 10 micrograms/ml cisplatin for 4 hr, cisplatin content in the KF cells was significantly higher than that in the KFr cells. When KF cells were incubated in the presence of W-7 (but not W-5), cisplatin uptake significantly increased, compared to cells treated with cisplatin alone. On the other hand, when KFr cells were incubated in the presence of 5 micrograms/ml W-7 or W-5, cisplatin uptake was significantly higher than uptake by KFr cells treated with cisplatin alone, being comparable to that by KF cells treated with cisplatin alone. Such an increase in cisplatin uptake seemed to bring about adjuvant effects to cisplatin of KFr cell proliferation in vitro. The KF tumor grown in nude mice took up 24.8 ng/g dry wt of cisplatin 4 hr after intraperitoneal administration. When cisplatin was administered with calmodulin antagonists, cisplatin uptake by the KF and KFr tumors was significantly increased, compared to that after treatment with cisplatin alone. In particular, the cisplatin uptake by the KFr tumor was about 2.5-fold higher than that by the KFr tumor treated with cisplatin alone. These results suggest that coadministration of calmodulin antagonists and cisplatin may be of use in patients with refractory ovarian cancer. PMID- 2227597 TI - Benign teratoma of the omentum and ovary coexistent with an ovarian neoplasm. AB - Benign cystic teratoma of the omentum is a rare abdominal tumor. Review of the literature describes seven reported cases of omental teratomas in association with ovarian teratomas. Our patient is a 68-year-old woman who presented with an asymptomatic abdominal mass and uterine prolapse. Ultrasound revealed a right sided, cystic and solid pelvic mass. CT scan revealed a second mass with calcifications situated along the right iliac crest. This is the first description of an omental teratoma in association with a benign ovarian cystic teratoma coexistent with a malignant neoplasm. Possible etiologies of the present case are discussed and additional literature investigated. PMID- 2227594 TI - Cancer of the uterine cervix: sensitivity and specificity of serum squamous cell carcinoma antigen determinations. AB - Between 1978 and 1989, 451 patients with cervical squamous cell carcinoma were referred to our department, of whom 143 experienced persistent or recurrent disease. Serial serum samples of the patients were analyzed for the presence of squamous cell carcinoma antigen (SCC). The incidence of elevated pretreatment serum SCC levels ranged from 37% in stage IB (N = 173) to 90% in stage IV (N = 19). Multivariate analysis showed that deep stromal infiltration and lymph node metastases were associated with significantly higher serum SCC levels. Serum SCC trends correlated with the course of disease: after treatment the sensitivity (percentage positive results in patients with persistent disease) was 79% and the specificity (percentage negative results in patients with no evidence of disease) was 91%. During follow-up, the sensitivity of the assay was 85.5% in patients with recurrent disease. However, the positive predictive value of a single serum SCC value greater than 2.5 ng/ml for tumor recurrence was only 49%. This figure rose to 76% when two consecutive elevations were determined. Stage and pretreatment serum SCC level were the only factors found to influence survival, using Cox's regression analysis with five pretreatment variables. PMID- 2227598 TI - Malignant hemangiopericytoma of the omentum presenting as an ovarian tumor. AB - Malignant hemangiopericytomas are usually found in the musculature of the extremities, the retroperitoneum, and the pelvis. Malignant hemangiopericytoma arising in the omentum is extremely rare. We recently experienced such a case, in which a malignant ovarian tumor was suspected preoperatively on the basis of the sonogram, CT scan, magnetic resonance image, and increased CA-125 value. Microscopically, the tumor showed many mitoses, increased cellularity, and cytologic atypia. The patient was treated with CAP combination therapy following resection of the tumor; however, an intraperitoneal recurrence probably due to implantation was recognized 11 months later. PMID- 2227599 TI - An unusual presentation of metastatic squamous cell carcinoma of the vulva. AB - Recurrent squamous cell cancer of the vulva metastasized via regional lymphatics. Hematogenous spread is late and unusual. A patient with metastatic disease presented with soft tissue mass in her thigh musculature. We believe this to be the first reported case of noncontiguous skeletal metastasis for this tumor. PMID- 2227600 TI - Papillary villoglandular carcinoma of the cervix. AB - Three cases of papillary villoglandular carcinoma of the cervix are presented. Each patient was multiparous and presented with abnormal vaginal bleeding. The mean age at presentation was 35 years (range 28-42 years). All patients were staged as FIGO IB and underwent radical Wertheim hysterectomy and bilateral pelvic lymphadenectomy. Disease was limited to the cervix in two patients and extended to involve the lower uterine segment in one patient. There was no evidence of microscopic spread to the lymph nodes. Previous reports that examined patients with papillary villoglandular carcinoma of the cervix found them to have a favorable prognosis. Treatment implications are discussed. PMID- 2227601 TI - Successful treatment of small intestine fistula with somatostatin analog. AB - A patient who developed an entero-neovagina fistula after total pelvic exeneteration is presented. When traditional conservative therapy appeared to be failing, addition of somatostatin analog resulted in a successful outcome. PMID- 2227602 TI - Incisional recurrence of squamous cell cervical carcinoma following operative staging. AB - A patient with FIGO Stage IIB cervical carcinoma underwent an extraperitoneal lymphadenectomy with exploratory laparotomy and washings for surgical staging. Intraperitoneal tumor was found. Seven months later, the tumor recurred as a subcutaneous nodule in the surgical incision. The implications of this recurrence are discussed. PMID- 2227603 TI - Retention of endometrial sensitivity to hormones after radiation therapy (RT) for cervical cancer in premenopausal patients. PMID- 2227604 TI - Growth hormone levels in maternal serum during pregnancy. AB - Maternal growth hormone (GH) levels during pregnancy have been variously reported to be suppressed or, more lately, to be increased. In an attempt to clarify this point, maternal GH levels were estimated with two modern GH polyclonal radio immunoassays (RIAs) and a new monoclonal enzyme-linked immunoassay (ELISA). The Cambridge Medical Diagnostics RIA and the more specific bioMerieux RIA gave similar results in control non-pregnant patients with raised GH levels, while the monoclonal ELISA gave slightly lower values. The bioMerieux assay gave results about 10 times higher than the Cambridge assay during pregnancy, at 12-61 ng/ml at 16-20 weeks and 47-153 ng/ml at 28-39 weeks (total n = 27). These high 'GH' levels did not correlate with maternal levels of prolactin or human placental lactogen. It is presumed that some unknown GH-like molecule(s) are being estimated in this assay, possibly the recently discovered human chorionic GH. That this is not pituitary GH was confirmed by the monoclonal ELISA, by which GH levels were almost undetectable during pregnancy. PMID- 2227605 TI - Perinatal outcome in HIV-infected pregnant women. AB - We have observed 74 HIV-seropositive and 48 HIV-seronegative drug-addicted women and 22 HIV-seropositive nondrug-addicted pregnant women during pregnancy and we report their perinatal outcome. 8 out of 96 HIV-seropositive patients had hematological signs of immunodeficiency and 2 of these patients were symptomatic belonging to CDC class III. We recorded 2 early and 3 late spontaneous abortions, no intrauterine fetal death and 3 neonatal deaths. Seropositive patients had 3 malformed babies, seronegative patients had 1. All these women had a high incidence of premature delivery and intrauterine fetal growth retardation: seropositive patients had a higher incidence of fetuses small for gestational age and a lower incidence of preterm delivery compared to seronegative patients, but the difference was not statistically significant. The incidence of malformation was comparable to the general population: 3 malformed babies were born to HIV positive drug-addicted mothers, and 1 to a seronegative drug-addicted mother. These findings do not support the hypothesis of a direct detrimental effect of HIV on perinatal outcome. Consequences of fetal exposure to maternal HIV infection involve mostly postnatal life and development of acquired immunodeficiency. PMID- 2227606 TI - First trimester live pregnancy and subsequent fetal loss. Impact of transcervical CVS and colonization of the cervix. AB - A consecutive series of 224 women undergoing transcervical chorionic villi sampling (CVS) were analyzed for the presence of cervical microbes. The outcome of pregnancy was related to age, number of aspirations and to the presence or not of microbes. The CVS group was compared to a group of 200 women with live fetuses at 8-11 weeks of gestation not undergoing CVS (ultrasound, US group). In the US group the miscarriage rate was 8.5% with 5.9% occurring after the 16th week of gestation. In the CVS group 20.3% ended as a miscarriage, 28.9% of these after the 16th week. There was no correlation between miscarriage rate and maternal age in the US group. In the CVS group younger women had a prominent rate of fetal loss. In the present study the risk of fetal loss after CVS was associated with a previous history of spontaneous abortions, with several aspirations performed, and with bacterial colonization of the cervix--candida and gardnerella excluded. PMID- 2227607 TI - Amniotic fluid findings in women with high levels of chlamydial antibody. AB - A study was undertaken to examine possible transplacental passage of Chlamydia trachomatis from pregnant women who were seropositive for chlamydia, but with no cervical C. trachomatis infection. Forty asymptomatic pregnant women, scheduled for diagnostic amniocentesis at 15-19 weeks of gestation, were tested for the presence of high serum IgA and IgG chlamydial specific antibodies and for cervical chlamydia infection. Five (12.5%) had both high serum IgA and IgG antibody levels and 10 (25%) had high serum IgG antibody levels. Overall, 15 (37.5%) had high serum chlamydia specific antibody levels (all were free of cervical chlamydial infection). The evaluation of the amniotic fluid specimens of these 15 seropositive pregnant women, who were free of cervical chlamydial infection, proved negative for direct C. trachomatis antigen detection and for chlamydial IgA and IgG specific antibodies. These negative results could be attributed to the lack of transplacental passage of C. trachomatis or to the antimicrobial activity of amniotic fluid against C. trachomatis, which has been previously described. The discrepancy between maternal infection and maternal serum antibody levels may suggest that the serologic test does not predict the presence of an antigen in the cervix. PMID- 2227608 TI - Steroid hormone receptors in pelvic muscles and ligaments in women. AB - Using monoclonal antibody assay techniques estrogen receptors (ER) and progesterone receptors (PgR) were quantitated in female pelvic floor muscles, urogenital ligaments and uterus (myometrium). Receptors were detected in all these structures. In addition qualitative assessment showed distinct nuclear staining in the same structures. ER and PgR were not found in the musculus rectus abdominis with either method. The findings provide a rationale for estrogen treatment in women with urogenital disorders. PMID- 2227609 TI - Ovarian pathology in chronic pelvic inflammatory disease. AB - One hundred and sixty-six ovaries of the women of childbearing age suffering from chronic pelvic inflammatory disease (PID) were studied histologically and compared with normal ovaries. The number of mature follicles, cystic atretic follicles, follicular cysts, corpora lutea of menstruation, regressing corpora lutea, and corpus luteum cysts were calculated for each ovary. The main difference between ovaries in chronic PID and normal controls was increase in the number of cystic follicles and follicular and corpus luteum cysts in PID. This phenomenon is explained by the altered blood supply in PID-involved ovaries covered by adhesions containing numerous blood vessels. Chronic PID did not influence the growth of follicles, and their ability to ovulate. PMID- 2227610 TI - Transvaginal ultrasound is an effective method for screening in polycystic ovarian disease: preliminary study. AB - To assess the usefulness of transvaginal ultrasound scanning (TVS) for screening in polycystic ovarian (PCO) disease, we symptomatically and endocrinologically compared 9 cases (group A) with PCO noted by transabdominal ultrasound scanning (TAS) with 8 cases (group B) with PCO noted by TVS only. No difference in the mean value of LH/FSH ratio, E1/E2 ratio and testosterone was observed between the two groups. However, the frequency of endocrine abnormalities, menstrual disorders and hypertrichosis in group A was significantly more than in group B. Therefore, we suggest that the stage of PCO noted by TAS is more progressive than that noted by TVS only and TVS is useful for screening of PCO disease. PMID- 2227611 TI - Effect of combined treatment with phenylpropanolamine and estriol, compared with estriol treatment alone, in postmenopausal women with stress urinary incontinence. AB - Twenty-nine postmenopausal women with slight to severe stress urinary incontinence and estrogen deficiency symptoms in the urogenital tract were treated with estriol, p.o. 4 mg once daily, and either phenylpropanolamine (PPA), p.o. 50 mg twice daily, or placebo for periods of 6 weeks according to a randomized double-blind crossover schedule. At urodynamic recordings the maximum urethral closure pressure increased by 22% with combined treatment (p less than 0.001) and an additional effect of PPA to estriol was shown (p = 0.022). The pressure transmission ratio increased, by about 15%, with both treatments (p less than 0.07). The number of leakage episodes was reduced by 28% with combined treatment (p = 0.007), but not with estriol alone (p = 0.08). Both combined treatment and estriol alone reduced significantly (p less than 0.01) the urinary incontinence complaints. Twelve women (43%) preferred combined treatment, while 7 (25%) preferred estriol alone. In women with initially slight to very severe urine loss, combined treatment reduced also (p = 0.02) the amount of urine loss, measured at a standardized physical stress test. Signs of estrogen deficiency in vulva, vagina and urethra were reduced, 75% (p less than 0.001) or 65% (p = 0.001) with estriol given in combination with PPA or alone. Maturation index of both urethral and vaginal epithelium displayed significant changes. It is concluded that the combined treatment, PPA + estriol, by affecting both the muscular and mucosal factor of the urethra, is more effective than estriol alone for treatment of female stress urinary incontinence in the postmenopausal ages. PMID- 2227612 TI - Treatment of large fibroids with high doses of gestrinone. AB - Twenty-four women with large, myomatous uteri, measuring between 218.7 and 2,920 cm3 were treated with gestrinone, a tri-enic steroid with antiestrogen and antiprogesterone properties. In order to saturate the receptors of the large myomata, the doses used to treat these women were twice the recommended dosage of 2.5 mg, 3 times weekly, used to treat smaller tumors. The treatment lasted 6 months to 1 year. In all cases there was a reduction in uterine volume. In the 24 patients, the mean uterine volume of 724.9 cm3 on admission decreased to 450.73 cm3 at 6 months. For 14 patients treated for a full year, the mean uterine volume of 689.73 cm3 decreased to 329.22 cm3. Menstruation was suppressed in all patients by the end of the 2nd month of treatment. Episodic bleeding occurred in 6 patients but in only 1 did this last longer than 1 week. Other symptoms such as pelvic discomfort and dysuria disappeared or were significantly alleviated by the 2nd month of treatment. Side effects included seborrhea, acne, nervousness, myalgia and arthraglia, hoarseness and mild hirsutism but all these symptoms were promptly reversed following discontinuation. The mean increase in weight was 3.4 kg in 6 months. No menopausal symptoms such as hot flushes and depression developed during this trial. Six patients complained of excessive sweating. Blood glucose creatinine, blood urea nitrogen, alkaline phosphatase, pyruvic and glutamic transaminases remained within the normal range. PMID- 2227613 TI - Measurements of ascorbic acid and glutathione in exfoliated cervicovaginal epithelial cells of smokers and women with cervical dysplasias. AB - This report emphasizes the ability to quantify ascorbic acid (AA) and reduced glutathione (GSH) levels in exfoliated cervicovaginal epithelial cells obtained by a lavage technique. Sixty-two women with abnormal Papanicolaou smears underwent colposcopic examinations. Colposcopic lesions were biopsied and histopathologically graded. Marked variations in the number of cells and in the levels of AA and GSH were observed. In cigarette smokers, the number of exfoliated cells retrieved was significantly higher (p less than 0.05, by Student's t test). The simultaneous investigation of biochemical and virologic parameters in exfoliated cervicovaginal epithelial cells, in conjunction with the known cytopathologic and epidemiologic risk variables, provides a novel approach to elucidate factor(s) that may inhibit or promote cervical carcinogenesis in designed prospective studies. PMID- 2227614 TI - Fetal and uteroplacental flow velocity waveforms in the expectant management of placental abruption. AB - The change in flow velocity waveforms was assessed by Doppler ultrasound in the course of evolution of placental separation. The velocity changes reflected a high response to blood flow in the placental circulation along with decreased cerebral vascular resistance. PMID- 2227615 TI - Post-remission treatment in acute myeloid leukemia: chemotherapy or autologous or allogeneic bone marrow transplantation. PMID- 2227617 TI - Transferrin receptor expression in the human placenta. AB - Iron transport from the mother to the fetus is mediated by transferrin receptors located at the maternofetal interface of the placenta. Transferrin receptors bind iron-loaded transferrin molecules from the maternal plasma, thus allowing iron uptake by trophoblastic cells which then deliver the metal to the fetal plasma. We have measured the transferrin receptor content in the placentas from 16 normal term pregnancies and investigated the relationships between transferrin receptor expression and non-haem iron content, as well as maternal and fetal iron status. Transferrin receptor content was evaluated indirectly by determining the transferrin binding capacity of a placenta extract. Transferrin receptor content of the placenta ranged from 20 to 154 micrograms/g of tissue, with a mean value of 96 +/- 37 micrograms/g. The mean non-haem iron content was 78 +/- 11 micrograms/g of tissue, corresponding to 47 +/- 10 mg for the whole placentas. The amount of transferrin receptors in the placenta was found to be inversely related to the amount of non-haem iron (r = 0.64; p less than 0.025). No significant relationship was observed between each of these two parameters and the iron status of either the mother or the fetus. We conclude that placental non haem iron, which represents a storage form of this element, is likely to play a regulatory role in the expression of transferrin receptors, and consequently in the process of iron uptake by the placenta. PMID- 2227616 TI - High expression of multinucleated giant cells in cultures of peripheral blood cells from HIV infected patients. AB - Multinucleated giant cells (MGCs) were detected in cell lines established from peripheral blood lymphocytes of patients with: (a) acquired immunodeficiency syndrome (AIDS) and lymphadenopathy syndrome (LAS), (b) chronic active hepatitis (CAH), (c) papular acrodermatitis (PA) negative for hepatitis B virus antigens but positive for EBV, and (d) epidermolysis bullosa acquisita positive for EBV. All the cell lines established, including those established from AIDS and LAS patients, were examined for the presence of human immunodeficiency virus (HIV) by indirect immunofluorescence with monoclonal antibodies directed against the HIV antigens p17 and p24 and for the presence of reverse transcriptase. All the cell lines were found to be negative for HIV. While the cell lines obtained from AIDS patients still express MGCs after more than two years in culture, their supernatants are negative for reverse transcriptase activity and carry phenotypic markers characteristic of B cells. From the LAS and chronic active hepatitis patients we obtained a monolayer of adherent cells almost completely represented by MGCs that lasted for six and four months, respectively. After this period of time a proliferation process took place. Both the cell lines obtained carry B cell phenotypic markers, but MGCs are still a characteristic only for the LAS derived cell culture. Non infected patients or normal subjects express MGCs only during the early stage of the cultue. The correlation between the presence of MGCs and a retrovirus infection is discussed in the light of the role of MGCs in the pathogenesis of AIDS. PMID- 2227618 TI - Average life expectancy of heterozygous beta thalassemic subjects. AB - In order to define the lifespan of heterozygous beta thalassemic subjects as compared to non thalassemic subjects, the authors prospectively studied all patients deceased during a period of 76 months at St. Camillo Hospital of Comacchio (Ferrara), located in the Po delta, a region with high prevalence of thalassemia minor. No statistically significant differences were found in the average life expectancy between the thalassemic and non thalassemic groups. PMID- 2227619 TI - Idiopathic myelofibrosis: a retrospective study of 103 patients. AB - The clinical course of 103 patients (50 males, 53 females; median age 59 years) with idiopathic myelofibrosis (IMF) seen at our hospital between 1967 and 1986 was analyzed retrospectively. Common symptoms and signs at the time of diagnosis were: myelofibrosis (96%), splenomegaly (84%), anemia (81%), osteosclerosis (45%), malaise (41%) and leukocytosis (41%). It was possible to follow the majority of patients without treatment or with transfusion therapy only for prolonged periods of time. The use of cytostatic drugs and radiotherapy was restricted as much as possible. Probably due to this treatment strategy the incidence of acute leukemia was low (5%). Major thromboembolic complications were seen in 19% of the patients. Median survival of the patients was 4.3 years. The prognostic influence of several disease parameters determined at the time of diagnosis was tested: age, sex, leukocytes, platelets, hemoglobin, reticulocytes, LDH, ANP-score, spleen size and percentage of peripheral blood blasts + promyelocytes had no significant influence on the length of survival. Osteosclerosis, a presumed sign of advanced disease, was not correlated with survival either. PMID- 2227620 TI - Incidence and clinicopathological heterogeneity of HIV-related non-Hodgkin's lymphoma. AB - The characteristics of 14 HIV-seropositive patients with NHL consecutively observed between 1984 and 1988 at our Institution are described. Patients belonged to a known population of 1242 HIV-seropositive individuals in whom the incidence of NHL was 1.13%, significantly higher than in age-matched controls (P less than .0001). Within this population, a previous diagnosis of ARC or AIDS, but not of LAS, was the only significant risk factor for the development of NHL (P less than .0001). According to the status of HIV infection at the time of NHL diagnosis, two groups of patients could be clearly identified with different clinicopathological features and prognosis. In fact, NHL developing in 7 patients previously affected by ARC or AIDS, presented as localized, extranodal disease, predominantly in the CNS; large cell histology, peripheral blood cytopenia, severe immunodeficiency and poor prognosis further distinguished this subgroup. Conversely, NHL developing in 7 patients with either asymptomatic HIV seropositivity or LAS, more often presented as disseminated disease both in nodal and extranodal sites, with Burkitt's-type histology. Cytopenia was uncommon and immunodeficiency was significantly less severe. In this subgroup complete remission (CR) was achieved with aggressive treatment in 6 of 7 patients. No relapses occurred but two opportunistic infection-related deaths were observed. Four patients are alive 6-34 months after CR, two of whom show newly developed opportunistic infections. PMID- 2227621 TI - Chronic B-cell lymphoproliferative disease: relationship between immunophenotype and clinical stage. AB - We analyzed the immunophenotype in 34 cases of B-CLD referred to our observation over a 13-month period. In 25 patients the classical phenotypic pattern of B-CLL was observed; in 9 cases clinical, morphocytochemical, and histologic findings were consistent with CLL but differed in phenotype. The results indicate that four immunophenotypic subgroups related to CD5 and FMC7 expression may be identified within B-CLL. Clinical correlations in these cases suggest that B-CLL with anomalous phenotypes are more frequently diagnosed at a later stage than classical B-CLL. Furthermore, while the percentage of CD3+ cells did not vary among the subgroups, a comparison of the CD4/CD8 ratio disclosed marked differences. PMID- 2227622 TI - High doses of ara-C and m-AMSA in the treatment of refractory acute non lymphocytic leukemia. AB - From November, '85 to March, '87, 17 patients (12 males and 5 females, median 28 years) with resistant or relapsed ANLL received HiDAC (3 g/m2 c.i. 3 hs every 12 hs, day 1-4) + m-AMSA (100 mg/m2 i.v. day 5-7) as salvage therapy: 8/17 patients (47.1%) achieved CR, 7/17 (41.1%) were resistant and 2/17 (11.8%) died during induction; 8/10 relapsed patients achieved a 2nd CR, while all 7 primary resistant patients failed to. Median period of PMN less than 0.5 x 10(9)/l was 28 days, median period of PLTS less than 30 x 10(9)/l was 25 days. All patients had infections during aplasia. Median CR duration was 6.6 months, while median survival of responders was 10.6 months. Two patients with severe induction related complications relapsed after 2 and 5 months, respectively: 1 patient underwent BMT and relapsed after 21 months; 5 patients, 4 of whom had received a prior ABMT during 1st CR, underwent ABMT: 3 died from ABMT related toxicity and 2 relapsed after 8 and 18 months, respectively. We conclude that HiDAC + m-AMSA is highly effective in relapsed, but not in resistant patients with acceptable hematologic and extra-hematologic toxicity. The role and modalities of ABMT in prolonging a 2nd CR are at present controversial. PMID- 2227623 TI - Automatic differential blood counting in plasma cell leukemia. AB - The authors report a case of primary plasma cell leukemia and two cases of multiple myeloma with a large number of circulating plasma cells. The display of Technicon H-1 shows a very high "cloud" in the area of large unstained cells. A massive invasion of the basophil area was not found. Differences between these results and those found in different lymphoid leukemias are discussed. PMID- 2227624 TI - Combined factor VIII and factor XI congenital deficiency: a case report. AB - Combined congenital defect involving both Factor VIII and XI is a very rare disorder. We describe a case of combined Factor VIII and XI deficiency in which the propositus has a mild hemophilia A and inherited a Factor XI deficiency from the father. Moreover, we report on the benefit of DDAVP administration to the patient during a bleeding episode. PMID- 2227625 TI - Ticlopidine in the treatment of thrombotic thrombocytopenic purpura: report of two cases. AB - The observation of two clinical cases make possible an evaluation of the potential therapeutic activity of platelet function inhibitors in thrombotic thrombocytopenic purpura (TTP). In particular, the clinical and hematological effects of ticlopidine (TC), employed alone in two TTP patients, are reported. The mechanism of action of this peculiar antiplatelet drug is mainly represented by the inhibition of fibrinogen binding on the platelet surface. In the first patient, a 45-year-old female in whom plasma-exchange (PE) and corticosteroids (C) led to a partial remission (platelets 80 x 10(9)/l), treatment with TC at a dose of 750 mg/day was carried out, and after 6 weeks a normal platelet count was observed. A complete remission was maintained for 31+ months, even after reduction of the TC dose to 250 mg/day. In the second patient, an 18-year-old female affected by relapsing TTP, a complete remission obtained with PE and C was maintained for 19 months in concomitance with TC treatment, started at a dose of 750 mg/day and lowered to 250 mg/day. After 11 months of treatment at this low dosage there was a relapse (platelets 20 x 10(9)/l), but the increase of the TC dose to 750 mg/day in a few weeks induced a complete remission again. These data, in accord with a few other recent preliminary reports, suggest that TC, even alone, may play an interesting role in the management of TTP patients. PMID- 2227626 TI - Fine needle aspiration biopsy of a splenic hemangioma. A case report with review of the literature. AB - A 33-year-old man was hospitalized for hyperpyrexia and pain in the left upper quadrant of his abdomen. Abdominal ultrasound showed a mass in the inferior pole of the spleen. A computed axial tomography of the abdomen and a liver and spleen scintigraphy confirmed a space-occupying lesion in the spleen but were not able to define its nature. A FNAB performed during abdominal ultrasound showed cells with elliptic nuclei and elongated pale blue cytoplasm, separated from each other by empty spaces of varying width. The presence of a hemangioma or lymphangioma of the spleen was suspected. A splenectomy was performed. The histologic findings were compatible with a cavernous hemangioma. After a review of the literature, the role of FNAB of the spleen is discussed as a reasonable diagnostic approach that assists the clinician in making therapeutic decisions in the management of the space-occupying lesions in the spleen. The possibility of differentiating benign from malignant lesions is pointed out, particularly those of endothelial nature. Finally, the differential diagnosis between hamartoma and hemangioma of the spleen is discussed. The two words, in times past, were often used for the same lesion, producing a confusion of names in literature. PMID- 2227627 TI - Wernicke-like encephalopathy after autologous bone marrow transplantation. AB - A 15-year-old boy with non-T ALL in early 2nd remission was autografted using a regimen with busulphan 4 mg/kg/day, po, from day -9 to -6, and cyclophosphamide 50 mg/kg/day, iv, from day -5 to -2. During busulphan administration he experienced a few generalized seizures, and starting on day 25 post ABMT he developed a progressively severe neurological symptomatology characterized by nystagmus, right VIth cranial nerve palsy, truncal ataxia and, finally, confusion and coma. MRI showed lesions in the periaqueductal gray matter, thalamus, mammillary bodies and putamen. Within 24 hours of treatment with thiamine he improved dramatically, but during the following weeks permanent neurologic damage with memory deficit, truncal ataxia and nystagmus became evident. To our knowledge this is the first case of Wernicke's encephalopathy reported after BMT. We suspect in this case a contribution of busulphan to the development of the syndrome. PMID- 2227628 TI - Bone marrow transplantation in an HIV positive thalassemic child following therapy with azidothymidine. AB - The authors report their experience on allogeneic bone marrow transplant in an HIV seropositive thalassemic child. Before transplant a treatment with Azidothymidine was performed with the aim of reducing the viral load. Engraftment took place but, later, an explosive upsurge of viral disease occurred with encephalitis, positivation of the P24 antigen, proliferation of opportunistic infections and an increase of the IgG level. Furthermore the failure of CD4+ cell recovery was also observed. This case underlines that bone marrow transplantation can have a successful engraftment in HIV seropositive patients, but this doesn't modify the course of the infection. PMID- 2227629 TI - Thrombotic thrombocytopenic purpura. Clinical course and response to therapy in seven patients. AB - The clinical characteristics, treatment and outcome are reported in 7 patients with 8 episodes of thrombotic thrombocytopenic purpura (TTP). In all episodes a complete remission was reached. Plasma exchange therapy was successful as single treatment in two episodes. Combination with other treatment modalities, however, was necessary in six episodes, in which a complete hematologic and clinical remission was obtained with antiplatelet therapy (4 X), and with antiplatelet therapy and corticosteroids (2 X). PMID- 2227630 TI - 1,25-Dihydroxyvitamin D3 in the treatment of idiopathic thrombocythemia and myelofibrosis. AB - The effect of treatment with 1,25-dihydroxyvitamin D3 administered at the dose of 1.50-3.00 ug/day for at least 12 months was evaluated in three patients with idiopathic myelofibrosis and in five patients with idiopathic thrombocythemia. This treatment did not cause any significant change in the hematological values or the clinical course of the myeloproliferative diseases in any of the patients. Based on these data, treatment with 1,25-dihydroxyvitamin D3 in non toxic doses seems to be of doubtful benefit in patients with these disorders. PMID- 2227632 TI - T cell defect in a case of sinus histiocytosis with massive lymphadenopathy and extranodal involvement. PMID- 2227631 TI - Norfloxacin versus cotrimoxazole for infection prophylaxis in granulocytopenic patients with acute leukemia. A prospective randomized study. AB - Norfloxacin (NOR) or cotrimoxazole (TMP/SMX) were randomly administered to 59 granulocytopenic patients with acute leukemia for prevention of bacterial infections. Nineteen NOR patients (65%) and 22 TMP/SMX patients (73%) complained of febrile or infectious episodes during the study. The mean incidence of febrile complications per patient was higher in the TMP/SMX group: 1.05 vs 0.68 (p less than 0.05). Eleven of 16 microbiologically documented infections in the TMP/SMX group and 7 of 11 in the NOR group were caused by gram negative bacilli (GNB). NOR recipients had fewer days of fever, fewer days on parenteral antibiotics and a lower proportion of time spent febrile. Fecal surveillance cultures showed intestinal GNB colonization in 42/80 specimens in the TMP/SMX group (resistant strains: 93%) and in 8/75 specimens in the NOR group (1 resistant strain). Overall, NOR seems to be effective in eradicating GNB from the digestive tract without selection of resistant strains and in preventing febrile episodes in neutropenic patients. PMID- 2227634 TI - Analysis of factors affecting acute transformation in chronic myelomonocytic leukemia. PMID- 2227633 TI - Kinetics of serum TK and LDH during therapy for AML. PMID- 2227635 TI - Central indwelling catheter to prevent phlebosclerosis by peptichemio in patients with multiple myeloma. PMID- 2227636 TI - Fungal infection and haematological malignancies: a report about association therapy with amphotericin B and 5-flucytosine in primary lung involvement. PMID- 2227638 TI - [Primary tensile strength of newer and modified tendon sutures. A comparative in vitro study]. AB - Modified with new methods of flexor tendon sutures compared with the Kessler technique on cadaveric tendons are reported. The authors offer some suturing methods which allow active movement of the reconstructed flexor tendons. PMID- 2227637 TI - [Primary and secondary covering of defects of the hand using pedicled and free forearm flaps]. AB - Our experiences in eight radial forearm flaps as free flaps or island flaps are shown. Indications for the use of these flaps in the hand are shown and advantages and disadvantages mentioned. Since 1980, when Muhlbauer and others brought the idea of this flap from China to Europe, its use as an island or as a free flap has been mentioned repeatedly. Generally the safety of this flap and the ease of harvesting are stressed. Other advantages are the long vascular pedicle and the large size of the vessels. These advantages are a temptation to use this flap for indications where it is not really suitable and where other methods are better. It has to be stressed that the donor site is not without problems from an esthetic and functional point of view. The removal of the radial artery, even when replaced by a venous graft may have some drawbacks. PMID- 2227639 TI - [Measurement of the tensile force exerted on the flexor tendons of the hand]. AB - Immediate postoperative active motion after flexor tendon repair is a recurring theme in hand surgery. In the present study the authors determined the tensile stress of the sutured tendon subjected to active motion by the use of cadaveric hands and a tensiometer. The force necessary to draw forth the proximal stump was also measured. A tendon suture which can resist two kilo-ponds tensile force seems to allow active motion of the reconstructed flexor tendon. PMID- 2227640 TI - [Controlling and supporting apparatus of the deep finger flexor tendon and the long extensor tendon of the thumb. Clinico-anatomical analysis]. AB - Full function of finger flexion requires an intact pulley system. After destruction of the pulleys, reconstruction over the metacarpal head (A1) and over the center of the proximal and middle phalanges (A2, A4) should be carried out. Calculations on a computer model suggest that the reconstructed pulley must hold the tendon close to the underlying bone. Width of the pulley and distance from the next proximal or distal joint of the inserted pulley are of minor functional importance. The amount of maximum load on the pulley, exceeding the tension of the tendon, must be considered in operation and postoperative treatment. The extensor pollicis longus tendon lies at the dorsal tubercle (tubercle of Lister) within an osseous gliding surface, where it changes direction. The deviation angle depends on the radiocarpal position and causes, in addition to the usual tension, a pressure stress to that part of the tendon. A graphical analysis of statics, based on X-rays, demonstrates maximum loads on the gliding surface. They can increase in relation to the tension force of the tendon to about 50% in the antero-posterior and to 100% in the radioulnar projection. Densitography of the distal radius shows a maximum of density where the dorsal tubercle is most prominent. Nutritional problems of that tendon are predisposed by that particular mechanical stress. Therefore spontaneous rupture of the extensor pollicis longus tendon in patients with rheumatoid arthritis or after fracture of the distal radius occurs, though infrequently. In the case of immobilization, slight ulnar abduction within the radiocarpal joint remarkably reduces the tension and pressure stresses on the tendon. PMID- 2227641 TI - [Monitoring of an acute compartment syndrome of unusual etiology using MRI (magnetic resonance tomography) and MRS (magnetic resonance spectroscopy)]. AB - The authors report on an acute compartment syndrome occurring symmetrically in the extensors of both forearms. The etiology of this unique compartment syndrome, not previously described, could be attributed to the inhalation of a propane butane gas mixture, low in oxygen, while sleeping, in combination with external compression of both forearms, due to the patient's head lying on both forearms while sleeping. Ischemic damage to muscles was precisely located using non invasive MRI (Magnetic Resonance Imaging). The extent of cellular damage due to ischemia after fasciotomy and healing by secondary intention was quantitatively assessed using non-invasive 31P-MRS (Phosphorus Magnetic Resonance Spectroscopy). The results correlate with the clinical and histological findings and indicate a bioenergetic regeneration of the ischemic skeletal muscle's cells. PMID- 2227642 TI - [Acute carpal tunnel syndrome and tendon rupture of the long flexor muscle of the thumb as a rare complication of a scaphoid pseudoarthrosis. Case report]. AB - The authors demonstrate a case of a scaphoid pseudarthrosis leading to an attrition rupture of the flexor pollicis longus tendon, tenosynovitis and haemorrhage into the carpal tunnel causing recurrent symptoms of an acute carpal tunnel syndrome. Every acute carpal tunnel syndrome is an emergency requiring instant decompression of the carpal tunnel. If success with conservative treatment of acute carpal tunnel syndrome is questionable, early operative relief of the median nerve is the safest procedure. PMID- 2227643 TI - [Reposition instrument for Bennett's fracture-dislocation]. AB - A special hook and plate can be used to adapt small central fragments in the open reduction of Bennett's fracture-dislocation. The hook is positioned behind the small central fragment and compression exerted between the hook and a plate attached to the opposite side of the base of the first metacarpal bone using an adjustable nut, thus holding the fragments together. The reduction device simplifies X-ray controls and internal fixation with Kirschner wires. PMID- 2227644 TI - [Apparatus for the cooling and preparation of extremity parts in vitro. Application in replantation surgery]. PMID- 2227645 TI - [Long-term results following implantation of breast prosthesis with a polyurethane coating]. AB - 42 of 63 cases of bilateral augmentation mammaplasty using polyurethane-covered prostheses, so-called Ashley "Natural-Y" prostheses were seen 15 to 17 years after the primary operation. Two implants had previously been replaced by Cronin gel type prostheses for various reasons. The 84 breasts which were examined in follow-up compared well with breasts augmented with other devices as far as capsular contracture was concerned. The extreme difficulty of removing these implants because of the deterioration of the polyurethane cover makes any further use of these implants unjustifiable. PMID- 2227646 TI - [Construction of a neo-clitoris in male-to-female transsexuals]. AB - To preserve the ability of orgasm in male-to-female transsexuals we retain the glans-penis and the corpus cavernosum urethrae as a unit. The glans-penis will be placed into the anterior wall of the neo-vagina under the symphysis as the neo clitoris. PMID- 2227647 TI - [Strategic planning in the hospital today--a mandatory process]. AB - Since the beginning of this decade strategic planning has become a common analytical method in nonprofit organizations, as well as in the business sector. In the nonprofit sector it has been implemented mainly in hospitals and universities. From experience, it is clear that strategic planning has contributed to the hospital's survival, improved performance, implementation and control. However, such good results have only followed correct planning and implementation, with emphasis on the business elements of an economic firm, such as marketing and budgetary planning, a control system and funding with increasing integration of "mathematical business" models. Recent studies have proved that strategic planning is a necessary condition for the survival of nonprofit organizations in a competitive environment. Experience demonstrates that modification of the business model of strategic planning in the nonprofit sector has significant advantages for both public and private sectors. We describe the way strategic planning is performed in hospitals, as well as relevant modification and limitation of the process. Our message to Israeli hospitals is that those which do not prepare themselves systematically for change, may find survival impossible. PMID- 2227648 TI - [Multiple enteral fistulas in peritoneal tuberculosis]. AB - A 40-year-old Ethiopian man had abdominal pain for a year and a half, diarrhea and weight loss. Multiple enteral fistulas were diagnosed by X-ray and colonoscopy. During investigation, the differential diagnosis was between Crohn's disease, intestinal lymphoma and intestinal tuberculosis. Therapeutic trial with corticosteroids was unsuccessful. At operation peritoneal tuberculosis was diagnosed and several entero-enteric fistulas were found, but there were no other intestinal lesions nor other foci of tuberculosis. Intestinal fistulas complicating peritoneal tuberculosis are rare in comparison with enteral tuberculosis, lymphoma or Crohn's disease. After the fistulas were closed surgically and antitubercular treatment given, the patient recovered, returned to his normal weight, and had no complaints. PMID- 2227650 TI - [Statewide system approach to the organization of trauma care services--a way to improve the quality of care to the injured]. PMID- 2227649 TI - [A thermostable toxin-producing E. coli and infantile diarrhea]. AB - An E. coli strain producing only a thermostable toxin (ST) and belonging to serogroup 0153 (ETEC 0153; ST) was isolated from the stools of 9 infants with diarrhea, 4 of them premature, during the last half of August, 1988. All the 4 prematures passed frequent fluid stools. In 5 of the 9 infants, other pathogens were found in addition to the ETEC strain, including rotavirus, Plesiomonas and Shigella sonnei. Until recently, ETEC strains like that described were considered rare all over the world. During the past 2 years ETEC strains belonging to that serogroup and toxin type were reported as a major cause for infantile diarrhea in Spain in 5 outbreaks. Infantile diarrhea caused by an ETEC strain in Israel is reported here for the first time. PMID- 2227651 TI - [Immune neutropenias of infancy and childhood--update on diagnosis and treatment]. PMID- 2227652 TI - [Idiopathic atrial fibrillation and occult thyrotoxicosis]. PMID- 2227653 TI - [Extracorporeal renovascular surgery]. PMID- 2227655 TI - [Non-convulsive status epilepticus and the importance of emergency EEG]. PMID- 2227654 TI - [Chest pain: cardiac or esophageal?]. PMID- 2227656 TI - [Routine breast examination and early detection of hypertension and diabetes mellitus by primary care physicians ]. AB - Breast cancer is the leading cause of cancer mortality among women is Israel. On average, 1 in every 12 women develops the disease. While breast self-examination has not proved effective, and routine mass mammography is at present unavailable to the population at large, regular routine breast examination by primary care physicians can effectively screen a large fraction of this country's population. In order to do so, full acceptance of the procedure by women and their physicians is required. This study examines the attitudes and practice of primary care physicians with regard to routine breast examination, and compares them with routine detection of hypertension and diabetes mellitus. A structured questionnaire was distributed to all 97 Kupat Holim (workers' federation sick fund) primary care physicians in the Negev. They included 40 family physicians (FP), board-certified or completing specialization, and 57 general practitioners (GP), not board-certified. There was no difference in response rate between the 2 groups (47%). Nearly all physicians perform routine examinations for detection of hypertension (100% of the FP and 96% of the GP) and diabetes mellitus (91% and 74%, respectively). Of the FP, 96% consider routine breast examination as the task of the primary care physician, versus only 68% of the GP. Accordingly, 92% of the FP stated that they routinely perform the procedure, but only 52% of the GP. Being an FP was positively related with the performance of breast examination, while seeing a large number of patients per clinic session and low job satisfaction were negatively associated with it. PMID- 2227658 TI - [Early detection of diseases in primary care]. PMID- 2227657 TI - [Leukergy 1990]. PMID- 2227659 TI - [Meningitis, shock and rash in a 16-year-old girl]. PMID- 2227660 TI - [Polymorphous ventricular tachycardia in acute myocarditis ]. AB - Myocarditis may present with a variety of electrocardiographic patterns. However, polymorphous ventricular tachycardia (PVT), potentially a highly malignant ventricular arrhythmia, has not been described in acute myocarditis. As far as we know, this is the first report of this arrhythmia in that condition. It is characterized by unusual resistance to both the common pharmacological and nonpharmacological approaches. This report of a 28-year-old woman demonstrates the role of PVT as a potential cause for sudden death among patients with subclinical myocarditis. PMID- 2227661 TI - [Laryngeal neuroendocrine carcinoma (carcinoid)]. AB - Neuroendocrine carcinoma (carcinoid), is a rare laryngeal malignancy with aggressive behavior. The 5-year survival rate is only about 10%, mainly because of distant metastases. We describe a patient with neuroendocrine carcinoma of the larynx, large cell type, without evidence of regional or distant metastases. Treatment included total laryngectomy and adjuvant radiotherapy to the neck. There was no evidence of disease at 6-month follow-up. PMID- 2227662 TI - [Patient status evaluation using severity scores in the general intensive care unit]. PMID- 2227663 TI - [Human values and medical ethics]. PMID- 2227664 TI - [Hemoptysis]. PMID- 2227665 TI - [Policy with regard to laxatives]. PMID- 2227666 TI - [Extracorporeal shock wave lithotripsy for gallstones]. AB - Biliary stone disease is common in most western societies, among whom gallstones are present in approximately 15-20% of adults. 40-60% of all persons with gallstones are asymptomatic, but 30-50% of them develop symptoms over a period of 2-5 years. For decades, cholecystectomy was the only solution. In the past decade new options, such as oral dissolution, direct dissolution, invasive endoscopy and lately lithotripsy and adjuvant treatment with oral dissolution agents, have become available. This paper summarizes the rationale of lithotripsy, its indications and complications, the impressive results of its use abroad and the authors' year of experience with 110 patients. Immediate fragmentation was achieved in 90.3%. Complete dissolution after 1 month was seen in 20%, after 3 months in 38.5% and after 6 months in 61.6%. After 1 year of treatment 85.8% of our patients were stone-free. Experience abroad, as well as our own, shows that lithotripsy and oral dissolution can be the treatment of choice in a selected group of patients with symptomatic gall stones. PMID- 2227667 TI - [Effect of hemodialysis on hemodynamic assessment and cardiac flows determined by Doppler echocardiography]. AB - 25 patients with end-stage renal failure were studied by different echocardiographic techniques before and immediately after hemodialysis using M mode, 2-dimensional and Doppler echocardiography. Preload reduction after dialysis was manifested by a decrease in body weight, in left atrial diameter and in the left ventricular end-diastolic dimension. Doppler flow patterns immediately after dialysis showed reduction in early diastolic velocities across the atrioventricular valves and increase in the flow velocities across the semilunar valves and the peripheral A-V fistula. The flow velocity integral, calculated by Doppler echocardiography, was lower after dialysis. Significant improvement in left ventricular myocardial function after dialysis was correlated with reduction in afterload and increase in myocardial contractility. PMID- 2227668 TI - [Diabetic hand syndrome in juvenile diabetics]. AB - 247 patients with juvenile diabetes mellitus, aged 3-37 years, were examined for diabetic hand syndrome. 68 (27%) had 1 or more of the manifestations of diabetic hand syndrome. In 45 (18%) flexion contractures were found, 41 (17%) had skin changes resembling those of scleroderma and digital sclerosis, and 12 (5%) suffered from trigger finger. We found an association between diabetic hand syndrome and diabetes control as evaluated by serial levels of hemoglobin A1c measured during the years of follow-up. A high relative risk for microvascular complications was found in those who had diabetic hand syndrome, compared to the others. The relative risk for retinopathy was 2.5 times greater in patients with diabetic hand syndrome (p less than 0.001). These results show that diabetic hand syndrome is a common presentation of juvenile diabetes mellitus and can be utilized as a marker for some of its complications. PMID- 2227669 TI - [Intracavernous pharmacotherapy for organic impotence in the elderly]. AB - Vasoactive intracavernous pharmacotherapy (VIP) has become an important tool for the treatment of erectile impotence. The average age of patients treated has been only 59 years and the oldest, 79. We describe the results of VIP in the oldest group of patients described. 28 men, 65-84 years old (average 70), were treated for organic impotence with intracavernous injections of a mixture containing 25 mg/ml papaverine HCl and 0.83 mg/ml phentolamine. Treatment was started with an injection of 0.25 ml of the mixture, with increments of 0.25 ml until there was functional erection, or untip a total of 1.5 ml was injected. Full erection was obtained in 46.5%, while in 40.0% there was a mild nonfunctional erection and in 13.4% no reaction to treatment. The response to the injection was similar in the different etiologic groups. There were no complications, such as prolonged erections or adverse reactions to the drugs injected. We conclude that elderly men seek help in order to have normal sexual function. We therefore think that VIP has a definite place in the treatment of impotence of the elderly. PMID- 2227671 TI - [Posterior approach for excision of sacral chordoma]. AB - Chordoma is considered to be a malignant, fatal tumor. According to most authors it constitutes between 1-4% of all malignant bone tumors. In 50% of the cases it is located in the sacrum, in 35% in the cervical spine and skull, and in 15% in the thoracic spine and elsewhere. It is an aggressive, locally invasive, slowly growing tumor. Although metastases are rare, when they occur they are of an anaplastic type, especially in the lungs, liver, regional lymph nodes, skin and muscles. Chordoma is a rare tumor, and its location and slow growth often result in delayed diagnosis. Complete excision of the chordoma was formerly considered impossible. There is often local recurrence, and often, by its very nature, excision results in neurological defects. Lately, there is more optimism regarding complete cure, due to more advanced surgical methods. We present a 66 year-old man in whom a tumor developed in the sacrococcygeal area and the right buttock. The tumor was diagnosed by CT, MRI and biopsy as a chordoma of the sacrum, without intra-abdominal infiltration. He was operated through a posterior approach, with complete resection of the tumor, including almost the whole sacrum and the coccyx. We consider this approach simpler than the abdominal-dorsal approach, which in cases of intra-abdominal infiltration is necessary. We regard this simple incision as a significant advance in the treatment of this condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227670 TI - [Delayed spontaneous rupture of the bladder following augmentation enterocystoplasty]. AB - Delayed spontaneous rupture of the urinary bladder following augmentation enterocystoplasty is a serious life-threatening complication of uncertain etiology. Multiple factors are believed to contribute to the mechanism of bladder perforation. Ruptured augmented bladders share a common urodynamic pattern of high leak point pressure of the urethra, with sensory and mechanical tolerance of high filling pressure. This combination seems to be the main predisposing factor for spontaneous perforation. Other risk factors, including catheter trauma during intermittent self-catheterization, urinary retention due to mucus retention or noncompliance with the catheterization protocol, chronic infection, and decreased sensation of bladder filling, may play roles in the mechanism of rupture. Clinically, patients present with sepsis, abdominal pain and distension, ileus, fever, oliguria and peritoneal irritation. The diagnosis is made on low pressure cystography, although failure of cystography to demonstrate extravasation is not unusual. Aggressive surgical treatment consists of immediate exploration, primary repair of the perforation, drainage of the perivesical space, suprapubic cystostomy and broad-spectrum antibiotics. Longterm management includes a strict intermittent catheterization schedule, anticholinergic therapy and urodynamic evaluation. Failure to achieve a low pressure storage reservoir by conservative means entails an increased risk of recurrent perforation. In such cases further surgical intervention should be considered. We present a 21-year-old paraplegic man 5 months after augmentation enterocystoplasty who required operation because of spontaneous rupture of the augmented bladder. Spontaneous delayed rupture of the bladder should be considered in the differential diagnosis of acute abdomen in patients after augmentation enterocystoplasty. Early surgical treatment and subsequent monitoring of the low pressure reservoir are recommended. PMID- 2227672 TI - [Toxocariasis in Emek Israel]. AB - Toxocariasis is a rare zoonotic disease in Israel. It usually affects children under the age of 10. Toxocara canis and Toxocara catis are common parasites among dogs and cats which affect man when he ingests the eggs of these helminths. We describe 3 children with different clinical presentations of the infestation. A 6 year-old boy had pain in the muscles of the limbs and diffuse patches in the right lower lobes on X-ray; a 7-year-old girl presented with a limp; and a 3-year old boy had abdominal pain and a maculopapular rash covering the whole body. All 3 had eosinophilia. They illustrate the importance of toxocariasis in the differential diagnosis of eosinophilia. PMID- 2227673 TI - [Metastatic Serratia marcescens endophthalmitis]. AB - A case of metastatic Serratia marcescens (SM) endophthalmitis is described in a 57-year-old diabetic woman, after amputation of her leg above the knee because of peripheral vascular disease. SM cultured from the infected surgical stump was the source of septic emboli to her right eye and lungs, causing endophthalmitis and pneumonia. The ocular infection did not respond to appropriate antibiotic therapy and evisceration was required. SM infection can cause endophthalmitis refractory to antibiotics, and it should be aggressively treated when SM is cultured from any infected site. PMID- 2227674 TI - [Increased use of drugs in sports]. PMID- 2227675 TI - [Autoantibodies as specific markers for autoimmune diseases]. PMID- 2227676 TI - [Transfusion-associated graft-versus-host disease and its prevention]. PMID- 2227677 TI - [Clinical and pathophysiological aspects of thromboembolic phenomena in cancer]. PMID- 2227678 TI - [Intestinal obstruction in cancer patients]. PMID- 2227679 TI - [Continuous monitoring of mixed venous oxygen saturation: physiology, clinical utility, indications]. PMID- 2227680 TI - [Communicating with families of children with cerebral palsy]. PMID- 2227681 TI - [Epidemiology of basketball injuries]. AB - The players of an elite basketball team were followed during the course of a season which included 71 games and 250 training sessions. All injuries were noted and were correlated with age, height and other physical parameters of the players, as well as with degree of fatigue during games and during training sessions. The lower extremity was the most common site of injury. Ligamentous injuries of the knee are more common in basketball than in soccer players, but they have fewer meniscal injuries than the latter. However, the upper extremity, especially the hand, is more frequently injured in basketball than in other sports. The age, height and personality of the player affect the injury pattern. PMID- 2227682 TI - [The diagnostic value of CT and MRI studies in brain-stem tumors]. AB - The combination of lower cranial nerve palsy and contralateral motor impairment, presenting subacutely and following a progressive course in a child or young adult, suggests the possibility of brain-stem tumor. However, if the CT scan is normal, the diagnosis of multiple sclerosis or a vasculitis is frequently considered. Since CT scans may miss lower brain-stem tumors, MRI is recommended as the definitive diagnostic test in such cases. PMID- 2227683 TI - [Extreme bilirubinemia in hepatitis A associated with G6PD-deficiency]. AB - In patients with G6PD-deficiency and hepatitis A infection, the clinical picture can resemble fulminant hepatitis. We describe 2 patients with this association. Bilirubin concentrations were over 50 mg/dl in both, but they recovered completely. PMID- 2227684 TI - [Epiglottitis in adults]. AB - Acute epiglottitis in the child is an emergency, well known to pediatricians, that requires rapid diagnosis and treatment. Aggressive treatment in recent years has markedly decreased mortality (17). Acute epiglottitis in adults has been thought to be rare, but lately numerous studies have shown an increase in the disease. We present 19 older patients, aged 13-72 (mean 44.7 years), with acute epiglottitis. A most important finding was the relatively long time from onset of symptoms until diagnosis, averaging 2.5 days. All the blood and throat cultures were negative, except for a single throat culture which yielded Pseudomonas aeruginosa. The most common presenting symptoms were severe sore-throat and dysphagia; half presented with some respiratory distress. Diagnosis was usually made on indirect laryngoscopy, but lateral X-ray of the soft tissues of the neck was found to be highly reliable. Treatment was usually conservative, including antibiotics, rehydration and steroids to alleviate edema. All patients were under strict observation for the first 48 hours, but only 1 required intubation. There were no deaths. PMID- 2227686 TI - [The seton in the treatment of trans-sphincteric anal fistulas]. AB - In most patients anal fistulas are of the intersphincteric type (Parks' classification). Treatment consists of simple fistulotomy. 10% of those with an anal fistula have the more complicated trans-sphincteric type. The treatment of such a fistula by primary fistulotomy is associated with a high rate of incontinence. A technique to avoid this complication is the use of the seton for gradual transection of the sphincteric fibers. 21 of 53 patients with anal fistula had a trans-sphincteric fistula, and all of them were treated with setons. Hospital stay was 2 days and was followed by 2-4 outpatient visits. 17 patients (85%) underwent the procedure without any complications and were cured. 3 (15%) had minor problems with continence, of whom 2 required emergency operation. In no case did the fistula recur. We find that the use of the seton after partial fistulotomy for complicated anal fistulas reduces the rate of incontinence caused by sphincteric transection and has a very low recurrence rate. PMID- 2227685 TI - [A respiratory health questionnaire for occupational screening]. AB - A Hebrew pulmonary health questionnaire was designed for occupational screening, based on the American Thoracic Society questionnaire but adjusted to conditions in Israel. It was designed for assisted completion using a computer, but can easily be modified to become self-administered. We propose that it be used here as the standard, occupational, pulmonary health questionnaire and as the basis for a standard, general purpose, respiratory health questionnaire. PMID- 2227687 TI - [Brown spider bite]. AB - The diagnosis of bite by the brown recluse spider, Loxosceles reclusus, is rarely based on absolute identification of the insect because the victims are usually bitten while sleeping or dressing. More often, the history, clinical findings and course of the bite lead to the diagnosis. For early confirmation up to 24 hours after the bite, the passive hemagglutination test can be used. For older lesions, the in-vitro lymphocyte transformation test is useful, but is available in only a few medical centers. Treatment of the bite of the brown recluse spider varies from conservative to more active approaches. Resting, local cooling, systemic antibiotics to prevent infection and mild anti-inflammatory drugs may be given. In the more active approach oral corticosteroids are added in the first 72 hours to the antibiotics, especially in massive bites with necrotic centers greater than 2 cm in diameter, or when there is systemic loxoscelism. Recently, good results have been reported with Avlosulfon (dapsone), which is claimed to cure necrotic cutaneous ulcerations, presumably by reducing the activity of polymorphonuclear leukocytes. Other treatments include specific antivenin, (of limited use because it must be administered shortly after the bite), and surgery to prevent spreading of the venom. We describe 3 cases of brown spider bite with typical clinical presentations in adults aged 20-40 years. 2 were treated with corticosteroids and antibiotics and 1 with Avlosulfon and prednisone, all within 72 hours of the bite. 2 recovered completely within a few days, but the third treated with prednisone and antibiotics, developed an ulcer which healed only after several months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227688 TI - [Late pneumothorax: a complication of subclavian vein catheterization]. AB - Subclavian vein catheterization is safe as long as proper indications and contraindications are observed. In the hands of highly qualified personnel, subclavian vein catheterization has a minimum rate of complications. Pneumothorax is by far the most common complication of the procedure. We describe a 64-year old man who developed pneumothorax late after left subclavian vein catheterization. PMID- 2227689 TI - [The emergency room as a setting for clinical training]. AB - The undergraduate medical curriculum does not include supervised training in emergency services. Medical students and residents are expected to acquire skills and experience related to emergency medicine during their clerkships in the clinical wards. Consequently, Israeli medical graduates often have difficulty in coping with common situations in primary care and emergency medicine. In response to the perceived need of emergency training, we modified the undergraduate teaching program of the clinical clerkship. During their medical clerkship, students spent several weeks in the emergency ward. Residents were similarly assigned to the emergency ward on a rotating basis for 3-month periods. Both the positive feedback of the trainees and the practical relevance of the program and its feasibility, suggest that it may be a worthwhile addition to the undergraduate and graduate clinical curriculum. However, we have no data for evaluating the outcome. We feel that all aspects of emergency medicine should be included in the teaching programs of the various clinical specialties, and suggest that the emergency room should be used as a teaching setting during the clinical clerkship, the internship and residency training. PMID- 2227690 TI - [Selection of fetal sex: facts and myths]. PMID- 2227691 TI - [Malignant ovarian tumors in pregnancy]. PMID- 2227692 TI - [New antibiotics for gynecologic infections]. PMID- 2227694 TI - [Medical aspects of boxing]. PMID- 2227693 TI - [Chlamydial salpingitis--diagnosis and treatment]. PMID- 2227695 TI - [Mental aspects of physical activity]. PMID- 2227697 TI - [Balneological (Spa) therapy for rheumatic diseases]. PMID- 2227696 TI - [Immunotherapy for stinging insect allergy--update]. PMID- 2227699 TI - [Pitfalls in the diagnosis of brain-stem tumors]. PMID- 2227698 TI - [Chemical drug dependency and the medical community: a short circuit]. PMID- 2227700 TI - [Nephrotic syndrome, amyloidosis]. PMID- 2227701 TI - Pathogenicity and ultrastructural pathology of Eimeria debliecki (Douwes, 1921) in experimentally infected pigs. AB - It was confirmed, after experimental infection of 24 weaned pigs with different doses (200,000 and 4 mil.) of Eimeria debliecki oocysts that the developmental cycle of E. debliecki occurs in the anterior jejunum and after a high dose of oocysts also in the duodenum and anterior parts of the middle jejunum. Pathological changes characterized by a light atrophy of the villi, scarcely dispersed minute erosions of the epithelium in upper parts of the mucosa and an inflammatory response in the propria of the anterior jejunum were found in the area of the largest occurrence of developmental stages of E. debliecki (from 50 cm to 100 cm from the pylorus). An inflammatory infiltrate in the propria of the anterior jejunum from 3 DPI to 5 DPI contained a conspicuously large number of plasma cells with Russell bodies. Cellular changes were detected only in enterocytes with developmental stages of E. debliecki. Changes of the microvillous zone were observed in infected enterocytes; dilated mitochondria, free ribosomes and an increased number of residual bodies were found in the cytoplasm of enterocytes. The degree of the cellular changes of enterocytes was dependent on the maturity of the developmental stage of E. debliecki. Based on pathological changes observed by the use of light and electron microscopy, the coccidium E. debliecki is considered to be pathogenic for weaned pigs in spite it does not provoke a clinical infection. PMID- 2227702 TI - Laboratory diagnosis of acute toxoplasmosis by immunosorbent agglutination assay (IgM ISA). AB - A group of 401 patients suspected for toxoplasmosis was examined by the indirect immunofluorescent antibody test (IFAT). All patients positive in IFAT (176) were examined by the immunosorbent agglutination assay (IgM ISA). In the IgM ISA 154 of them were negative, 10 temporarily and 12 high-positive. Some of high-positive patients were examined repeatedly; decrease of high levels of specific IgM antibodies occurred 2-9 months after the first examination. For the IgM ISA antigen prepared from peritoneal exudate of experimentally infected mice was used. The antigen was stable at 4 degrees C or in liquid nitrogen at least 1 year. The IgM ISA combined with IFAT and IgM IFAT was proved satisfactory for the diagnosis of acquired acute toxoplasmosis and can be recommended for laboratories with lower capacity. PMID- 2227704 TI - Synopsis of type specimens deposited in the helminthological collection of the Institute of Parasitology, Czechoslovak Academy of Sciences, in Ceske Budejovice. II. Cestoda, Trematoda and Acanthocephala. AB - The paper comprises a list of the cestode, trematode and acanthocephalan type specimens deposited in the helminthological collection of the Institute of Parasitology, Czechoslovak Academy of Sciences, in Ceske Budejovice. These materials include a total of 7 species of cestodes, 16 species of trematodes, and 5 species of acanthocephalans. PMID- 2227703 TI - Effect of cortisone on Toxoplasma gondii infection studied by electron microscopy. AB - The ultrastructural features of cortisone effect on the early development and formation of Toxoplasma gondii tissue cysts were examined in the brains of experimental mice on days 8-47 post inoculation. The cortisone was injected subcutaneously into mice twice a week: 1) at the early acute phase, 5 days post infection, and 2) at the transition phase of development, 12 days post infection. The disturbed regulation of the host-parasite relationship due to the effect of cortisone showed itself in an increase of T. gondii tachyzoites, cystozoites, and cysts not only by intracellular but also by as yet not described extracellular division. The persisting parasitaemia induced by tachyzoites and the earlier development and differentiation of cysts resulted in the cyst rupture releasing a highly resistant antigen of cystozoite type. The toxoplasmic encephalitis had a lethal effect in all mice. The tachyzoites penetrated into many types of cells, but a predilection of development into cysts was detected in neurons and astrocytes. According to the character of host cells, two types of cysts arose: less resistant electron-transparent cysts in neurons often rupturing or budding and more resistant electron-dense cysts in astrocytes. PMID- 2227705 TI - Environment and host-parasite relationships in Monogenea. AB - The interest of a new approach in taking up the problems of host-parasite relationships with environment is proposed in terms of population biology. Two different integrating levels are considered: a microenvironment that corresponds particularly to the host and a macroenvironment corresponding to the whole host parasite system. Some examples are given that provide significant reasons in perceiving the biology of Monogenea under these aspects. To conclude we emphasize the importance of developing this new way for the study of hybrids models in relation to parental host systems. PMID- 2227706 TI - The systematical composition of the family Heteraxinidae and other allied families of Monogenea. AB - This paper briefly presents a system of Heteraxinidae and other allied small monogenean families of suborder Microcotylinea Lebedev, 1972 with the indication of specific composition of all taxa and diagnoses of some taxa; new families Megamicrocotylidae, Paramonoxinidae and Monaxinoididae are proposed. PMID- 2227707 TI - Caryophyllaeides ergensi sp. n. (Cestoda: Caryophyllidea) from Leuciscus Leuciscus baicalensis from Mongolia. AB - The tapeworm Caryophyllaeides ergensi sp. n. (Cestoda: Caryophyllidea) is described from Leuciscus leuciscus baicalensis from the River Selenga basin in Mongolia. It differs from the only hitherto recognized species of the genus C. fennica (Schneider, 1902), mainly in its extremely long uterus with coils extending anteriorly to anterior half, sometimes up to anterior third of the body of gravid specimens. PMID- 2227709 TI - Immunodiagnostics of Toxocara canis in suspected ocular and visceral manifestations. AB - Sera from patients with ocular and visceral manifestations of toxocariasis were tested by precipitin absorption (PAT), counter-immunoelectrophoresis (CIEP), indirect fluorescent antibody (IFAT) and ELISA. The ocular cases revealed a percentage of positivity of 36% by PAT, 0% by CIEP, 32% and 28% by IFAT with embryonated egg (EE) and frozen section antigens (FS) respectively and 40% by ELISA. The visceral cases revealed 44% positively by PAT, 24% by CIEP 52% and 48% by IFAT with EE and FS respectively and 52% by ELISA. Statistical evaluation was done to interpret the results. PMID- 2227708 TI - A new genus of capillariids from birds, Ornithocapillaria gen. n. (Nematoda: Capillariidae). AB - A new genus, Ornithocapillaria gen. n., belonging to the family Capillariidae and subfamily Baruscapillariinae is described and its diagnosis is given. The type species of the genus is Ornithocapillaria ovopunctata (Linstow, 1873) comb. n., other species are O. cylindrica (Eberth, 1863) comb. n., O. quiscali (Read, 1949) comb. n., and O. picorum (Rudolphi, 1819) comb. n. The new genus is characterized by a relatively large membranous pseudobursa, shape of processes supporting pseudobursa, and presence of a vulval appendage in female. It includes only species parasitic in the intestine of birds of the orders Passeriformes, Falconiformes, Strigiformes, and Piciformes. PMID- 2227710 TI - Francisella tularensis from ixodid ticks in Czechoslovakia. AB - A total of 26,478 ixodid ticks (935 pools) were examined by intracerebral inoculation of suckling mice. Six species of ticks were tested: Ixodes ricinus (23,470 individuals), I. trianguliceps (12), Haemaphysalis punctata (831), H. concinna (39), Dermacentor reticulatus (69) and D. marginatus (2,057). The ticks were collected largely by flagging vegetation, a substantial minority (4%) from animals. Three strains of Francisella tularensis were isolated, one each from I. ricinus (males, district Breclav, southern Moravia), D. reticulatus (males, district Breclav) and D. marginatus (engorged females collected from sheep in Roznava district, eastern Slovakia). D. marginatus and D. reticulatus represent new vector species for Czechoslovakia. PMID- 2227711 TI - Susceptibility of Mastomys natalensis to Brugia malayi following pretreatment with antifilarials. AB - Mastomys natalensis pretreated with diethylcarbamazine (DEC), levamisole or centperazine were exposed to the standard inoculum of infective larvae of Brugia malayi. Percentage 'take' of infection, duration of prepatent period, course of microfilaraemia and number of adult worms recovered were compared with those of untreated infected Mastomys (control). DEC and centperazine did not alter the 'take' (DEC/centperazine: 100%; control: 88.24%) and the average prepatent period (DEC: 105.44 days; centperazine: 105.18 days, control: 109.20 days). In levamisole pretreated animals on the other hand, the 'take' was much lower (68.18%) with extended prepatent period (125.87 days). However, unlike centperazine and control, the course of microfilaraemia was identical in DEC and levamisole pretreated animals. The average adult worm recovery was significantly high in centperazine pretreated animals being 14.09 as against 8.12, 7.46 and 8.42 in DEC, levamisole pretreated and control animals, respectively. PMID- 2227712 TI - Remarkable records of Anoplura from Czechoslovakia. PMID- 2227713 TI - A new species of the genus Chauhanellus Bychowsky et Nagibina, 1969 (Monogenea) from the gills of a sea fish Tachysurus dussumieri (Val.) from Andhra Pradesh, India. AB - Chauhanellus chauhani sp. n., collected from the gills of a sea cat-fish, Tachysurus dussumieri (Valenciennes) from the Bay of Bengal, off the coast of Kakinada, Andhra Pradesh, India is described and illustrated. It differs from the related species of the genus--C. oculatus, C. flexiosus, C. australis, C. nagibinae, and C. pedunculatus--in the shape and articulation of accessory piece with cirrus and in having a crescentic posteromedian process on its dorsal bar. It has five transverse hard structures on the ventral surface of peduncular region, by which it differs from C. oculatus and C. australis the latter have 10 11 and 3 such hard structures, respectively. PMID- 2227714 TI - A new Monogenean species, Bicotyle lucknowensis sp. n. (Monogenea: Heteraxinidae), from the Indian fish, Gudusia chapra (Ham.). AB - A new monogenean species, Bicotyle lucknowensis sp. n. of the family Heteraxinidae, has been described from the fish, Gudusia chapra (Ham.), from Lucknow, India. The new species is characterized by the number and shape of cirral spines, presence of an unarmed vagina and details of copulatory complex and haptoral armature. PMID- 2227715 TI - Antigenic characterization of rat louse Polyplax spinulosa. AB - Number and relative molecular weights of proteins in whole body homogenates of the louse, Polyplax spinulosa were determined using SDS-PAGE. 13 protein components from the total of 28 bands were defined as Con A binding glycoproteins. In immunoblotting sera of lice infested laboratory rats of BN strain specifically recognized 3 major protein components with r.m.w. of 77,000, 105,000 and 230,000 Da and from 6 to 8 minor protein components with r.m.w. of 31,000-180,000 Da. PMID- 2227716 TI - Experimental infection of ticks Ixodes ricinus with tick-borne encephalitis virus under different microclimatic conditions. AB - The influence of environmental temperature and relative air humidity on the development of ticks Ixodes ricinus and their infection rate with tick-borne encephalitis virus was studied. It was found that the temperature influenced significantly the development of ticks, but it did not influence their infection rate. To the contrary, the relative air humidity influenced the infection rate. It is assumed that the intrinsic factors play a primary role in the infection of ticks, while extrinsic factors have a secondary role; they are probably important at border values only. PMID- 2227717 TI - A record of gravid cestodes Bothriocephalus claviceps (Goeze, 1782) from the newts Triturus vulgaris (L.) (Amphibia). PMID- 2227718 TI - Occurrence of Coxiella burnetii, Rickettsia slovaca, and organisms resembling bacillary rickettsiae in their natural foci in Slovakia 20 years after their first detection. PMID- 2227719 TI - [Second messengers and protein phosphorylation in cellular signal transduction]. AB - Protein phosphorylation has been recognized as a major mechanism by which cellular functions are controlled by neurotransmitters and hormones. In this review, applications of molecular biological techniques to the analyses of regulatory mechanisms of protein phosphorylation by four major second messengers, cAMP, cGMP, diacylglycerol, and Ca2+, are described. 1) Complementary DNA of the regulatory subunit of the cAMP-dependent protein kinase was cloned and expressed in E. coli. Point mutations were introduced in order to analyze functional domains of the subunit. 2) The soluble isoform of guanylate cyclase was purified, and a cDNA of its 70-KD subunit was cloned. Cyclic GMP binding to purified cGMP dependent protein kinase was characterized using a rapid filtration assay. 3) Primary structure of the catalytic subunit of calmodulin-dependent protein phosphatase (calcineurin A) was determined and the presence of the second isoform of the enzyme was shown by the cDNA cloning technique. 4) The regulatory domain of the protein kinase C was expressed in E. coli. Analysis using site-directed mutagenesis revealed that a "zinc finger"-like structure is responsible for the binding of phorbol esters. In these studies, the molecular biological approach has proven to be useful for clarifying the molecular mechanisms of cellular signal transduction related to second messengers and protein phosphorylation. PMID- 2227720 TI - [Effect of Y-516 on the hyperactivity induced by dopamine injected bilaterally into the nucleus accumbens]. AB - The effect of Y-516 on the hyperactivity induced by dopamine injected bilaterally into the nucleus accumbens was compared with those of clocapramine (CCP), haloperidol (HPD) and chlorpromazine (CPZ). Dopamine (5-50 micrograms) injected into the nucleus accumbens induced a dose-dependent hyperactivity following pretreatment with nialamide (100 mg/kg, i.p., 2 hr). The hyperactivity induced by 10 micrograms of dopamine was antagonized by the i.p. administration of Y-516 (0.5-1.0 mg/kg), CCP (5-25 mg/kg), HPD (0.05-0.5 mg/kg) and CPZ (1-5 mg/kg) in a dose-dependent manner. The ED50 values of Y-516, CCP, HPD and CPZ were 0.85, 16.5, 0.098 and 2.53 mg/kg, respectively. These results suggest that Y-516 has a potential inhibitory effect on the mesolimbic dopaminergic system and may be a beneficial neuroleptic drugs. PMID- 2227721 TI - Changes in the behaviour of wild long-tailed macaques (Macaca fascicularis) after encounters with a model python. PMID- 2227722 TI - Obituary. Norman Creel. PMID- 2227724 TI - Incisor microwear and diet in three species of Colobus. AB - Examination of incisor microwear in three species of Colobus revealed that the predominantly folivorous C. badius more closely resembles C. satanas, a seed predator/folivore, than C. guereza, another predominantly folivorous species. This demonstrates that species of the same broad dietary category can have very different patterns of incisor microwear, indicative of differences in food procurement behavior and/or the physical properties of dietary items for some portion of the diet. Conversely, species of different categories can have microwear patterns that, superficially at least, are quite similar. The dissimilarity in incisor microwear between C. badius and C. guereza is mirrored to a certain extent in molar microwear, although the differences are not nearly so great on the molars. The differences between C. badius and C. guereza may involve different food items in the major, folivorous portions of their diets, or they may relate to differences in the very minor fruit and bark components. The similar microwear patterns of C. badius and C. satanas demonstrate that incisor microwear by itself is unreliable for assigning fossil species to broad dietary categories. Incisor microwear can be used to infer finer dietary distinctions in fossil species for which dietary category has been determined by other means. PMID- 2227723 TI - Comparison of auditory functions in the chimpanzee and human. AB - Absolute thresholds for pure tones, loudness, frequency and intensity difference thresholds and the resonance of the external auditory meatus were measured in chimpanzees and compared with those in humans. Chimpanzees were more sensitive than humans to frequencies higher than 8 kHz but less sensitive to frequencies lower than 250 Hz and 2- to 4-kHz tones. Difference thresholds for frequency and intensity were greater in chimpanzees than in humans. The resonance of the external ear was about the same in the two species. The effects of differences in hearing between species upon speech perception are discussed. PMID- 2227725 TI - Social climber: independent rise in rank by a female Barbary macaque (Macaca sylvanus). PMID- 2227726 TI - Female dominance in Lemur catta: more than just female feeding priority? PMID- 2227727 TI - Female dominance does not characterize all of the Lemuridae. PMID- 2227728 TI - Fourier analysis of the forehead shape of skull and sex determination by use of computer. AB - The forehead shape of the skull was quantified with the Fourier analysis method by using 100 male and 100 female radiographic lateral views of the skull, and sex difference in the forehead shape was studied. Furthermore to predict the sex of cranial specimens, an automated sexing computer system based on the quantification was created. The effectiveness of the system was evaluated by checking 56 male and 56 female specimens of skulls. This system was proved to discriminate male and female skulls from forehead shapes with 85% accuracy. PMID- 2227729 TI - Evaluation of a commercial radioimmunoassay kit for the detection of lysergide (LSD) in serum, whole blood, urine and stomach contents. AB - The Diagnostic Products Corporation Coat-A-Count radioimmunoassay kit for LSD in urine has been evaluated for use in forensic toxicology with a variety of sample types. The cut-offs (defined as the mean response of blank samples plus three standard deviation) for LSD in serum, haemolysed whole blood, urine and stomach contents were 0.06, 0.050-0.055, 0.18 and 0.18 ng/ml, respectively. Preliminary extraction of LSD from the samples is not usually necessary. The precision of the analysis and the recoveries from spiked samples were satisfactory. The cross reactivities of 2-oxo-LSD, lysergic acid methyl propylamide, lysergic acid monoethylamide and nor-LSD were estimated to be 11,6,2 and 1% respectively relative to LSD (100%). PMID- 2227730 TI - Avian vitreous humor concentrations of inosine, hypoxanthine, xanthine, uric acid, uracil and uridine as influenced by age and sex: their relevance as indicators of ante-mortem hypoxia. AB - An investigation was made to determine the effects of age and sex on postmortem concentrations (mumol/l) of inosine, hypoxanthine, xanthine, uric acid, uracil and uridine in the vitreous humor of chickens (Gallus domesticus). Five male and 5 female chickens were sampled each week from 0-10 weeks of age. Samples were collected at 0 and 24 h postmortem and analysed by HPLC. Hypoxanthine, uric acid and uridine were detected at both 0 and 24 h postmortem whereas inosine, xanthine and uracil were detected only at 24 h postmortem. Neither sex nor the sex X age interaction influenced the concentrations of the compounds investigated (P greater than 0.01). Age had a significant influence on the concentrations of all compounds at 24 h postmortem (P less than 0.0001). At 0 h postmortem, age significantly affected the levels of hypoxanthine and uridine (P less than 0.0001) but not uric acid (P = 0.014). All compounds occurred at higher concentrations at 24 than 0 h postmortem with the exception of uridine at 0 and 1 week of age. Previous studies using data confounded by age and postmortem sampling time have concluded that postmortem vitreous humor hypoxanthine concentration is a useful indicator of antemortem hypoxia. The results of this study cast doubt on that conclusion. Age and postmortem sampling time should be rigorously controlled when conducting quantitative analyses of these compounds in vitreous humor. PMID- 2227731 TI - Immunofluorescence demonstration of digoxin in human myocardial tissue and isolated rat cardiac myocytes with monoclonal antibodies. AB - The aim of the present investigation was to identify the morphological correlates of digoxin binding sites in human heart muscle tissue and isolated viable rat heart myocytes. Cardiac glycoside linked to myocardial cells was demonstrated by monoclonal digoxin specific antibody and by FITC-conjugated anti-mouse immunoglobin serum. This versatile immunofluorescence method can be used in diagnostic and experimental studies of cardiac glycoside binding. PMID- 2227732 TI - Routine phenotyping of native and desialyzed alpha 2HS-glycoprotein from blood stains. AB - The application of a polyacrylamide gel isoelectric focusing (PAGIEF) and immunoblotting procedure for the identification of native alpha 2HS-glycoprotein (AHSG) in routine casework blood stains has produced reportable results on 57.2% of samples. This reporting rate is lower than that for group specific component (GC) (83.8%) and phosphoglucomutase (PGM 1) (72.8%) phenotyping of the same samples. Blood stain samples were desialyzed with 1 U/ml neuraminidase, overnight at room temperature prior to PAGIEF in gels containing pharmalyte pH 5-6 and 2.5 M urea. Simple AHSG patterns were developed by immunoblotting. This procedure was five times as sensitive as the native AHSG method and desialyzation was reproducible over a range of incubation times and neuraminidase concentrations. The application of the desialyzed AHSG analysis to routine casework samples has resulted in a significant increase in the number of reportable results (762 reported out of 1027 samples). This reporting rate (74.2%) compares favourably with that for GC (79.1%) and PGH 1 (69.6%) phenotyping of the same samples. The three AHSG alleles (AHSG*1, 2 and 3) are clearly resolved after sample desialyzation and separation in gels containing pharmalyte pH 5-6 and 2.5 M urea. The sensitivity of desialyzed AHSG phenotyping approaches that of GC and this technique is worthy of inclusion in blood stain screening protocols of forensic laboratories in regions where the population has a limited range of rare AHSG alleles. PMID- 2227733 TI - Cocaine and fetal death. AB - Toxicologic screening for cocaine and its metabolites was performed on 103 cases of fetal death autopsied in the Office of Chief Medical Examiner, City of New York. In 64 cases cocaine or its metabolites were found in the blood or in the brain. Some malformations were also found. The study indicates that maternal use of cocaine may lead to abruptio placentae, abortion and fetal death. The importance of toxicologic examination in these deaths is emphasized. PMID- 2227734 TI - [The effect of the vertical bracket position on the orthodontic finish]. AB - As during orthodontic treatment and in particular during the phase of the precise adjustment of occlusion by applying the "straight-wire technique" problems arise as far as the vertical dimensions are concerned, the usual distances between the bracket slots and the edges of the incisors respectively the top of the cusps have been verified. Measurements were done on models at the end of treatment of ten patients treated with fixed attachments who may represent ideal occlusion as far as profile radiographs and gnathology were concerned. After regulation of the plane of occlusion the vertical distances between the slot base plane (parallel to the plane of occlusion) and the edge of the incisors respectively tops of cusps were measured by means of a modified parallelometer in connection with a special slot and tube support as well as a specially developed dial test indicator, while a maximum fit between bracket base and buccal crown surface was given. In case of the upper front brackets (torque + 22 degrees) large vertical measurement to the edge of the incisors were recorded, 8.25 respectively 8.33 mm). This may be attributable to excessive torque of the applied brackets. Only approximate figures for the vertical positioning for other teeth could be given, as anatomical variations have to be considered. PMID- 2227735 TI - [Glass ionomer cements as orthodontic bracket adhesives. An in vitro study with 4 glass ionomer cements (GIC) and 2 conventional orthodontic bracket adhesives as the comparative group]. AB - 240 orthodontic brackets were bonded to buccal surfaces of bovine teeth. As bonding material we used four glass ionomer cements without etching and two normal orthodontic bracket bonding materials with etching of enamel. Brackets of group 1 were tested with a material testing machine for shear and tensile strength after ten minutes. Brackets of group 2, 3 and 4 were tested after one day, 28 days and 98 days, respectively. In the average the bonding strength of glass ionomer cements was 50% less than the bonding strength of the comparison group with etching. The fracture of the bonding took place to 80% between the mesh base and the glass ionomer cements. Defects of the enamel surface were never observed. The bonding between mesh-base and glass ionomer cements has to be improved before the use of this bonding material can be recommended for the use in a busy practice. PMID- 2227736 TI - [Growth and therapy in Angle class II/2--a longitudinal cephalometric study]. AB - The influence of both growth and functional therapy with the U-Bow-Activator Type I on Angle class II subdivision 2 malocclusion is analysed in a cephalometric long term study. Findings concerning skeletal problems: 1. Therapeutically intended clockwise rotation of the mandible with vertically and sagittally controlled maxillary position, 2. achieving normal sagittal mandibular growth rates. Dental problems are improved significantly. The results obtained by functional therapy and growth proved to be stable in the post-treatment check ups. PMID- 2227737 TI - [Individual overbite behavior between the deciduous and permanent dentition]. AB - Manuals and relevant publications give rise to the impression that the formation of the overbite in the incisor region throughout its development is a process easy to overlook. Impressions of 108 cases were taken, one of the deciduous dentition and one of the permanent dentition 13 years later. A mathematic statistical analysis of objective measurable morphological dentition criteria were made and discussed. This shows that neither from the degree of overbite nor from any other feature of the deciduous dentition a prognosis concerning the extent of the final overbite of the permanent dentition can be derived. Changes throughout the development of the overbite are predominant. There are only little correlative coherencies among the morphological symptoms that can be applied quickly and easily for the prognosis in the clinical inspection. For estimating the development tendency longterm individualized observations are necessary. PMID- 2227738 TI - [The early treatment of children with cheilognathopalatoschisis--the orthodontic aspects]. AB - Maxillary alveolar arch morphology and growth was studied in 15 children with complete unilateral cleft lip and palate treated with passive orthopaedic plates. Nine patients were treated to the "Zurich concept" and compared to six children who had lip surgery and primary bone-grafting at about six months of age and complete palate closure at 18 months. Maxillary alveolar arch morphology was described at birth, at six months, at 18 months and at 4.5 years. After early orthopaedic treatment the alveolar and palatal cleft width decreased significantly, the major segment was relocated into a more normal position and the midline deviation was reduced, whereas the minor segment rotated towards the palate. PMID- 2227740 TI - [Fluorine and the dentition]. AB - In order to estimate the influence of fluorine (in drinking-water and air) on the occlusion 372 twelve-year-old children have been examined in four different localities with differing fluorine concentrations of drinking water and air. Apart from the determination of the fluorosis frequency and of the DMFt index, the number of children who do not require any orthodontic treatment according to the WHO recommendation has been determined. The degree of malocclusion has been defined by means of the Eismann-Masztalerz's method. There was observed that the optimal fluorine concentration in drinking water (0.7-0.9 mg/l) decreases the degree of malocclusion except for the crowding of the teeth whereas its concentration above the optimum (4.0-7.0 mg/l) as well as fluorine polluted air are one of the causes of crowding. PMID- 2227739 TI - [Initial attitudes to orthodontic treatment--the results of a practical and clinical questionnaire study (I)]. AB - 312 patients from one clinic and nine offices, between eight and 15 years of age treated with bionators, their parents and a control group were questioned on various aspects of their treatment. Findings regarding opinions about dentofacial appearance, initial motives and expectations are presented. Aesthetic motives proved preponderant by seeking treatment though the children's ability to verbally differentiate aesthetic concepts was poor. Above all, they expected visible treatment progress, absence of appliance-caused psychosomatic impairment and rather factual information than personal communication with the orthodontist. PMID- 2227741 TI - [The computer simulation of orthodontic tooth movements]. AB - A personal computer programme is presented which allows the prediction of orthodontic tooth movement under the influence of any given force and moment. The changes in position of the front teeth caused by the chosen forces appear on the monitor as a three-dimensional diagram and as a movie-like picture sequence. PMID- 2227742 TI - [The realization of a wear-timing device for clarifying the scientific questions presented in orthodontics]. AB - A timing device for removable orthodontic appliances is described. The measurement system includes a quartz digital clock at the timer. A reed switch serves as a sensor and is activated by a magnetic device fastened directly or by an orthodontic band to a molar tooth. A changeover reedswitch prevents manipulation by the patient. As a timing device the system provides great accuracy. The high-speed capability of the device permits further scientific application: Installation of two timing devices in a single Bionator permits selective timing (e.g. biting contact during wear of the appliance). PMID- 2227743 TI - [NMR-microscopic studies of the condylar cartilage of the temporomandibular joint]. AB - The objectifying of growth mechanisms of the TMJ is very important for orthodontic diagnosis, treatment as well as clinical research. Condylar cartilage of the TMJ from neonatal pigs was investigated on in vivo preparations by NMR microscopy. NMR-micro-pictures and histologic slide preparations of condylar cartilage were compared and discussed in connection with its implications for treatment with functional appliances. PMID- 2227744 TI - [Incidence and risk factors of malignant diseases]. PMID- 2227745 TI - [Body-packer syndrome. Psychotropic drug smuggle in the human body--discussion from the legal and medical viewpoint based on own patients]. AB - Body packing is the term used to describe the smuggling of drugs, usually cocaine or heroin, in special containers introduced within the body. Rupture of the containers leads to acute intoxication that often ends fatally. The possibility of drug poisoning should always be considered by the emergency or hospital physician confronted with an unconscious patient. If representatives of the law suspect anyone of drug smuggling and refer him/her to hospital, a knowledge of the legal position as laid down in particular in paragraph 81a and d of the StPO is of great importance. PMID- 2227746 TI - [Venous constriction by local administration of ruscus extract]. AB - The venoconstrictive action of the topical application of Ruscus extract was evaluated in a randomized, double-blind study involving 18 healthy volunteers, using duplex B-scan ultrasonography. Within 2 1/2 hours of the application of 4 to 6 g of a cream containing 64 to 96 mg Ruscus extract, the diameter of the femoral vein decreased by an average (median) of 1.25 mm, while placebo (base of the cream) was associated with a diameter increase of 0.5 mm (means) (p = 0.014). The decrease in venous diameter reflects good percutaneous absorption of the active substance. To date, venoconstrictive action has been demonstrable only indirectly with the aid of plethysmographic methods; it has now been measured directly under orthostatic conditions. PMID- 2227747 TI - [Growth of knowledge in immunology. From congenital immune deficiencies to common infection susceptibility]. PMID- 2227748 TI - [Congenital combined disorders of immune defense. Survival possibilities with early bone marrow transplantation]. AB - Congenital combined immunodeficiencies involving both T-cell- and B-cell dependent functions, are characterized by the early onset of life-threatening complications, usually of infections. Major clinical and laboratory findings in these disorders are presented, as well as therapeutic strategies involving bone marrow transplantation. PMID- 2227749 TI - [Acquired immunodeficiency]. AB - Secondary immunodeficiencies are much more frequent than primary immunological disorders. There are many etiologies, such as malnutrition, cytostatic drug therapy, burns, protein-losing conditions and infections. This review briefly considers the history of virus-induced immunosuppression. Today, measles and AIDS are the most important virus-induced immunodeficiency diseases. In rate instances, infections with Epstein-Barr virus can lead to hypogammaglobulinemia and B cell lymphomas. A viral etiology should always be considered in all cases of congenital and postnatally acquired immunological disorders. PMID- 2227750 TI - [Primary antibody deficiency syndrome. Improved life expectancy and immunoglobulin G substitution]. AB - Recurrent pyogenic infections are the leading clinical symptom in patients with antibody deficiency syndromes. In accordance with the WHO-classification at least nine different diseases are differentiated. In some cases diagnosis can be made simply by determining the immunoglobulin serum levels. Some diseases, such as Ig heavy chain gene deletions, are clearly characterized by molecular biological methods, while other terms, such as common variable immunodeficiency, cover a collection of different diseases with changes predominantly of B-cell functions. The main features of the antibody deficiency syndromes are described. In most cases adequate therapy can be achieved by IgG replacement therapy. PMID- 2227751 TI - [Erroneous methods in the care of children with immunodeficiencies. How can they be avoided?]. AB - Immunodeficiencies are often suspected, but altogether rarely diagnosed in time. A fatalistic attitude should not be allowed to justify inconsequential diagnosis and treatment, since nowadays, in a considerable percentage of these patients, life can be prolonged, or even a cure can be achieved, for example, by bone marrow transplantation. In order to meet the demands of modern pediatric immunology, structural improvements in the care of children with immunological disorders, as well as in the mediation of knowledge, are discussed. PMID- 2227752 TI - [Delayed-release verapamil hydrochloride in chronic atrial fibrillation. Reducing the heart rate]. AB - In an open clinical trial, the therapeutic effect of sustained-release verapamil hydrochloride was investigated in 40 patients with chronic atrial fibrillation. As required, the daily dose was increased from 240 mg to 480 mg. A clinically relevant, statistically significant decrease in the heart rate was observed in almost all the patients. Since only four patients experienced mild side effects, with no major clinical significance, the preparation has a positive benefit/risk ratio for the indication investigated. PMID- 2227753 TI - [Acute abdomen in anorexia nervosa. A case report]. AB - Anorexia is a common psychiatric condition of childhood and adolescence in which, apart from the striking psychopathology, somatic complications are frequently seen. The secondary somatic findings, however, are sometimes overlooked. This case report describes a 17-year-old girl in whom, during an episode of bulimia dilatation of the stomach occurred, which presented clinically as perforation. PMID- 2227754 TI - [Improvement in diabetes therapy. Interview by Heike E. Nahtke]. PMID- 2227755 TI - [Report on treatment with captopril and hydrochlorothiazide combination. Comprehensive therapy of hypertension]. PMID- 2227757 TI - [Do ambulatory patients complain more often?]. PMID- 2227756 TI - [Report of the 6th annual meeting of the European League Against Rheumatism, Athens, May 17, 1990. Naproxen--standard in rheumatism therapy. Confirmation of a tried and tested non-steroidal anti-rheumatic drug (NSAR)]. PMID- 2227758 TI - [NSAID indicated in all rheumatic diseases]. PMID- 2227759 TI - [Heart diseases as a cause of cerebral symptoms and syndromes]. AB - The causes, clinical indications and diagnosis and differential diagnosis of cardiac disorders which may lead to cerebral symptoms are illustrated on the basis of a review of the present day level of scientific research. Principally involved are cerebral ischaemias arising from cerebral embolisms or from reduction of cardiac output in cardiovalvular and myocardial disorders. The incidence of all embolisms of cardiac origin makes up 10% of all ischaemic cerebral infarcts, with auricular fibrillation, irrespective of its origin, mitral stenosis, myocardial infarct, mitral insufficiency and combined mitral valve defects, and, in younger patients, mitral valve prolapse, being, in this order of frequency, of primary clinical significance. The other cardiovalvular and myocardial disorders have, in comparison, a relatively low incidence of cerebral embolisms. Haemodynamically induced cerebral ischaemias frequently occur in the form of complications following acute cardiac arrest, in myocarditis and in case of primary cardiomyopathies resulting from cardiac insufficiency or complicating bradyarrhythmia. They are clinically apparent in the form of syncope, and other impairments of consciousness of various levels of seriousness with and without indications of cerebral origin, extending up to coma. In view of the high incidence of 25% of acute cerebral ischaemias in cases of cardiac disease, not only neurological but also detailed cardiological investigation is vital in all cases for a correct diagnosis and for the selection of a suitable course of treatment. Cerebral complications in bradyarrhythmia and endocarditis are discussed in the context of a review of the relevant literature together with consideration of their epidemiology, aetiology, pathophysiology and clinical profile. Pathological sinus-bradycardia, bradyarrhythmia absoluta, sinu-atrial and atrio-ventricular blockages, carotid-sinus and sick-sinus node syndrome, paroxysmal atrial tachycardia, AV-node tachycardias, and auricular fibrillation and flutter, taken as a whole, lead to cerebral complications affected patients in 5 to 10% of afflictions of the central nervous system occur in 50% of patients suffering from complete AV blockage and, at a not precisely definable frequency, in patients suffering from other bradyarrhythmias. In addition to transitory, uncharacteristic symptoms such as dizziness, vertigo, impairment of vision and balance, presyncope, syncope and Adams-Stokes syndrome dominate the clinical profile. Endocarditis, with an incidence of 0.01 to 0.05% in the overall population, results in central nervous system complications in 12 to 25% of cases on average.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2227760 TI - [Psychopathology of person misidentification--a multidimensional concept]. AB - The misidentification of person or Personenverkennung (PV) is provisionally redefined in this paper by focusing on four important points of view offered by German-speaking authors, all more or less based on an analysis of content. These deal with the extent of "craziness" of a PV (Leonhard), the degree of personal relationship of the person misidentified with respect to the patient (Kahlbaum/Pauleikhoff), the extent of the incorrect identification (Jaspers), and, lastly, the stage of stability shown by a PV at a particular point in time (Conrad). On this basis it is suggested that it may be best to initially call the PV simply a "delusion" with all further differentiation of types of PV carried out in light of a multidimensional psychopathological model utilizing various combinations of these four aspects of content. PMID- 2227761 TI - [Bone marrow transplantation]. PMID- 2227762 TI - [Solid and cystic tumor of the pancreas with prominent calcification]. AB - A case of a solid and cystic tumor of the pancreas is presented. The immunohistochemical study of the resected tumor revealed alpha 1-antitrypsin and neuron specific enolase positive malignant cells proliferating pseudopapillary around fibrovascular stroma. Prominent calcification was characteristic in the present case. PMID- 2227763 TI - [A case of acute potassium bromate intoxication]. AB - We experienced a case of a 44 year old man who had ingested potassium bromate solution for suicide attempt. Soon after the ingestion, nausea, vomiting, abdominal pain and diarrhea developed in him. Several hours later, he began to complain of auditory disturbance and, in addition, anuric acute renal failure occurred. Direct hemoperfusion and hemodialysis was performed on the patient for the treatment purpose. Five weeks later, he was released from hemodialysis procedure. Gradually, on the other hand, progressing anemia was observed until 90th hospital day, which slowly improved thereafter. Further, pruritus, lower leg pain, headache, tinnitus and loss of sense of taste, etc. were observed in the clinical course. Renal biopsy was performed on the 119th hospital day and the specimen showed the regenerative stage of acute tubular necrosis. In our case, acute renal failure was reversible and, many other clinical manifestations were observed. However slight anemia and irreversible severe auditory disturbance remained unimproved. PMID- 2227765 TI - Laser balloon angioplasty: potential clinical applications. AB - Coronary laser balloon angioplasty (LBA) is a new technique which permits application of heat (generated by the laser source) and pressure (by balloon inflation) to thermally weld tissue during coronary angioplasty (PTCA). The goal of LBA is to achieve a large, smooth arterial lumen, by thermal welding of dissection flaps, elimination of elastic recoil, elimination of vasospasm, reduction in platelet activation, desiccation of thrombus, and inhibition of smooth muscle cell proliferation (Table 1). The LBA system consists of a 50 watt continuous wave Nd:YAG laser with a wavelength of 1060 nm, and a modified coronary balloon angioplasty catheter with a 4.3 French shaft and a PET balloon measuring 20 mm in length and 2.5, 3.0 and 3.5 mm in diameter. For clinical use, laser doses ranging from 250 to 450 joules each are delivered over 20 seconds, to achieve adventitial tissue temperatures of 90 to 110 degrees C. The LBA technique is quite similar to that of conventional PTCA. The LBA catheter is usually positioned over a 0.014" guidewire through an 8 French guiding catheter. Once the laser balloon is in position, the balloon is inflated to a pressure of 4 atmospheres and the programmed laser dose is delivered over 20 seconds, followed by continued balloon inflation for an additional 20 to 40 seconds while the temperature of the arterial wall returns to normal. Conventional PTCA is virtually never necessary to improve lumen appearance and dimensions after LBA. LBA has been shown to be effective in the management of acute failure of PTCA, due to abrupt closure or severe dissection with impaired flow ("impending closure").(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227764 TI - [Rotation angioplasty of chronic coronary artery stenosis]. AB - Coronary artery occlusion of more than six months duration can only rarely be recanalized with conventional techniques. For this reason, rotational angioplasty, which has been successfully applied for occlusion of peripheral arteries, has been employed in modified form for recanalization of chronic coronary artery occlusion. Rotational angioplasty is based on the concept that the slowly revolving, dull and relatively thick head of the flexible rotation catheter will seek the path of least resistance which, even in the case of relatively old arterial occlusions, mostly represents thrombotic material. The elastic, high-torque rotational catheter constructed of several V2A spiral steel wires has an interior lumen for insertion of exchange guidewires up to 0.014" and injection of contrast medium and an olive-shaped head of V2A steel with a diameter of 1.3 to 1.6 mm. A protection catheter made of polyethylene with metal markers and conically-tapered tip provides variable stiffness of the rotating catheter and protection of the endothelium in the proximal vascular segment. The slow rotation of 200 r.p.m. is performed with a small electric motor. Between April 1987 and February 1988, rotation angioplasty was performed in 20 patients, 17 with occlusion of the right coronary artery, two with occlusion of the left anterior descending artery and one with bypass graft occlusion to the left anterior descending artery in whom a conventional guidewire through the chronic occlusion could not be advanced. The duration of occlusion, based on previous angiograms anginal complaints or myocardial infarction, ranged from one month to twelve years, in twelve patients more than six months. In all patients, the indication for revascularization was clearly established.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227766 TI - Intracoronary stents: clinical and angiographic results. AB - Limitations of current forms of coronary angioplasty including abrupt vessel closure and delayed restenosis have led to the development of alternative nonsurgical methods of coronary revascularization. By scaffolding the arterial dissection and smoothing the endoluminal surface, intracoronary stenting may obviate the need for emergency coronary bypass surgery in patients who develop abrupt vessel closure following coronary angioplasty. As primary therapy, its use may prevent or delay restenosis in high-risk patients; however, due to potential patient selection bias, controlled studies are needed. Currently available intracoronary stents are limited by varying degrees of inflexibility, radiolucency, and thrombogenicity. These limitations have resulted in the development of innovative stent designs using radioopaque tantalum filaments and aggressive pharmacologic treatment with antiplatelet and anti-thrombotic therapy following stent deployment. Current experimental investigation into the feasibility of intracoronary stent coating with genetically engineered endothelial cells or slow release antiproliferative agents, such as colchicine or methotrexate, may further serve to lessen the frequency of late restenosis. The optimal patient selection criteria for the use of the intracoronary stent is currently the subject of intense clinical investigation. PMID- 2227767 TI - [Coronary endoprostheses (stents)]. AB - Even before the introduction of transluminal balloon dilatation of coronary arteries, Dotter had conceived intravascular endoprostheses and, in 1969, published a report of his observations after implantation of a spiral-shaped support of surgical steel and nickel-titanium ligation in peripheral arteries of the dog. Interest in intravascular supports developed especially in consideration of frequent unsatisfactory long-term results after coronary angioplasty. Coronary artery occlusion is observed in about 5% of balloon dilatations due to dissection, thrombosis, spasm or a combination of these phenomena. The rate of recurrent stenosis after uncomplicated balloon dilatation is about 30%, that of recanalization of chronic occlusion or dilatation of stenosed bypass grafts about 50%. Stent technology: In order to provide a meaningful solution to unresolved problems of balloon dilatation, the ideal endoprosthesis must be rapidly and reliably implantable as well as sufficiently flexible to conform to vascular curvatures. It should have a low profile, must be biocompatible and not thrombogenic; it should be rapidly endothelialized with no excessive proliferatory stimulus. Rigid stents are limited in length; elastic stents display a better transition to normal coronary arteries. Negatively-charged metallic surfaces appear less thrombogenic than those positively charged, the former, however, are usually not free of corrosion. The generally positive charge of stainless steel, the most commonly used material, is tempered with a special surface treatment. Currently, materials under investigation are nickel-titanium, tantalum and biodegradable plastic. Of importance for endothelialization are the wall thickness of the stent and the relationship of material to pore size. Filaments of stainless steel measuring 0.09 mm in diameter are completely covered by neoendothelium within three weeks. In laboratory animals, within minutes after implantation, all three stents currently in clinical use are covered with a thin layer of thrombocytes and fibrin; after one day, endothelial-like and pseudoendothelial cells develop along the metal structures. After one week, there is a flow-oriented behaviour of the surface cell formation embedding the stent between neoendothelial and lamina elastica interna, a process which is complete in three months. The thickness of the neointimal proliferation may be dependent on the stent geometry and may vary between 0.09 and 0.4 mm.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2227768 TI - [Sinus node inhibitors in coronary surgery]. AB - In patients with coronary artery disease, rapid ventricular rates require adequate treatment since disturbed oxygen balance and ischemia may be incurred. By virtue of their isolated action on the sinus node, "specific bradycardic substances" have only negligible hemodynamic side effects and, accordingly, represent an alternative to other available rate-slowing drugs. The clonidine derivative, alinidine (N-allyl-clonidine) was used primarily as the specific bradycardic substance in our studies in patients at the time of aortocoronary bypass surgery. In addition to its rate-slowing properties, this substance also elicits an analgetic and anti-ischemic effect and, in a small percentage, it is metabolized to clonidine. The purpose of this study was to assess the effectiveness and hemodynamic actions of alinidine in the treatment of intraoperative heart rate acceleration and, in combination with the calcium channel blocker nifedipine, to evaluate its use for postoperative hypertension. The first study was performed in nine patients in whom, during aortocoronary bypass surgery, there was a heart rate increase in excess of 20% above the preoperative control value. Patients were excluded with impaired ventricular function, absence of sinus rhythm, concomitant increase in arterial mean pressure greater than 30%, hypovolemia, pulmonary capillary wedge pressure in excess of 15 mmHg as well as those with ECG changes precluding exact assessment of myocardial ischemia. In addition to the ECG, the following parameters were registered: heart rate, arterial pressure, central venous pressure and, with a semi-floating balloon-tipped catheter, pulmonary artery pressure as well as pulmonary wedge pressure. Cardiac output was determined with thermodilution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227770 TI - A prescription for high drug prices. PMID- 2227769 TI - Surgical treatment for chronic pulmonary thromboembolism. PMID- 2227771 TI - New drug legislation: a response from the pharmaceutical industry. PMID- 2227772 TI - Adverse drug reactions and the elderly. PMID- 2227773 TI - Drug approval and AIDS: benefits for the elderly. PMID- 2227774 TI - Geriatric medications in the pipeline. PMID- 2227775 TI - Employer-sponsored health insurance, 1989. PMID- 2227776 TI - Foundations' role in improving medication use by older persons. PMID- 2227777 TI - Prescription drugs, practicing physicians, and the elderly. PMID- 2227778 TI - Health promotion: continuing the national debate. PMID- 2227779 TI - Measuring progress in health promotion. PMID- 2227780 TI - The health of industrialized nations. PMID- 2227781 TI - Understanding the nature of addiction. PMID- 2227782 TI - Value of Medicare risk contracts. PMID- 2227783 TI - Experience of state drug benefit programs. PMID- 2227784 TI - Prescription drugs and the elderly. PMID- 2227785 TI - Managed care and a changing pharmaceutical industry. PMID- 2227786 TI - The role of mail service pharmacies. PMID- 2227787 TI - The Medicare Catastrophic Coverage Act: a post-mortem. PMID- 2227788 TI - Understanding the cost of a catastrophic drug benefit. PMID- 2227789 TI - [Repression of rearranged c-myc expression in murine cell hybrids]. AB - In hybrids SBW I and SBW II between S194 mouse plasmacytoma and BW5147 mouse T cell lymphoma, enhanced expression of the rearranged c-myc mRNA of heterogeneous sizes (1.8-2.4 kb) in S194 was markedly downregulated but expression of the non rearranged c-myc of 2.4 kb in BW5147 was not. Treatment of SBW I hybrid cells with cycloheximide augmented non-rearranged c-myc expression 2-4-fold but did not release the downregulated expression of the rearranged c-myc. Nuclear run-on assay showed that the high level of c-myc transcripts in S194 cells declined in SBW I cells comparable to the level in BW5147 cells. The results suggest that the downregulation of the rearranged c-myc in SBW I hybrid cells was at a transcriptional level rather than a posttranscriptional level. Methylation patterns of the rearranged c-myc in SBW I cells was the same as S194 cells. Treatment of the SBW I cells with 5-azacytidine, TPA or forskolin did not release the downregulated expression of the rearranged c-myc, suggesting no causative involvement of DNA methylation or protein phosphorylation in the downregulation. Higher DNase I sensitivity of the rearranged c-myc in S194 cells decreased to a similar extent to that of the non-rearranged c-myc after cell fusion with BW5147 cells. All these results suggest that expression of the rearranged c-myc was downregulated at the level of transcription in murine cell hybrids between a plasmacytoma and a T-cell lymphoma probably by changing the chromatin configuration around the gene from the open to the closed state. PMID- 2227790 TI - [Mechanism of reduction in proteinuria by cyclosporine A: effects on the glomerular anionic sites]. AB - To consider the mechanism of reduction of proteinuria by cyclosporine A (CYA) in the patient with intractable nephrotic syndrome, the effect of CYA on proteinuria and anionic sites (AS) of the glomerular basement membrane (GBM) was studied in puromycin aminonucleoside (PA) nephrotic rats. In addition the rats exogenously given human recombinant interleukin-2 (hrIL-2) every day repeated the same proteinuria were used. The PA nephrotic rats were made by single injection of PA 150 mg/kg excrete of urinary protein as compared 10 mg/day of urinary protein in the controls. The increase of urinary protein in the PA rats was inhibited by CYA10-20 mg/kg administrated orally from the day of PA injection for 15 days. To evaluate AS, the kidney were treated with a polyethyleneimine (PEI) staining method and the deposits in the lamina rara externa (LRE) of the GBM were counted on the electron micrographs. On the 15th day, in the PA rats, AS decreased greatly but were normal in the CYA-treated rats. On one hand, rats injected of hr IL-2 2.5 X 10(5)U/rat intraperitoneally for 14 days showed slight proteinuria on the 14th day, and the proteinuria was also inhibited by oral administration of CYA 25 mg/kg. As reduced in the rats treated with hrIL-2 as well as PA. The findings indicate that the proteinuria in the PA nephrotic rats and rats treated with hrIL-2 might result from reduction of AS and that the improvement of proteinuria in these rats by CYA might be due to the recovery of AS in the GBM. PMID- 2227791 TI - [Effects of volatile anesthetics on the cervical sympathetic nerve activity during acute hypoxemia or hypercarbia in dogs]. AB - Either hypoxemia or hypercarbia produces a significant change in the autonomic nervous system activity. Responses of the cervical sympathetic nerve activity (CSA) to acute hypoxemia and/or hypercarbia were studied in the absence and the presence of either halothane (H), enflurane (E), isoflurane (I) or sevoflurane (S). Multifiber potentials of CSA, EEG, ECG, heart rate, arterial blood pressure, arterial oxygen saturation (SaO2) and endtidal carbon dioxide concentration (FETCO2) were continuously monitored. CSA increased responding to acutely induced hypoxemia at a speed of -6-9% (SaO2)/min. The response of CSA was estimated in two ways as a function of SaO2; the threshold was determined at which CSA increased by 3% over the base level and the gain was determined by the slope of CSA increase divided by the SaO2 span. They were 92% and -1. 88 (Mean) in the absence of volatile anesthetics, respectively. The threshold and the gain decreased markedly in the presence of volatile anesthetics in a dose dependent fashion. They were 89.2% and -1.16; 81% and -0.74; 84.2% and -1.16 and 86.2% and 0.94 with 1MAC of H, E, I and S. At 1MAC, E and S suppressed CSA response significantly compared to equipotential H and I. CSA also increased responding to acutely induced hypercarbia at FETCO2 of 10%. The peak level increased 34% above the control value responding to hypercarbia in the absence of volatile anesthetics, though it was less than a half value of that induced by hypoxemia. The tonic levels of CSA were suppressed with increasing concentrations of volatile anesthetics. The base level and the peak level were 68.3% and 75%; 50.7% and 51.8%; 70.3% and 76.7%, and 55.5% and 63.2% with 1MAC of H, E, I and S. The inhibitory effects of 1MAC E on the CSA was significantly stronger than that of equipotential H or I. CSA did not respond against hypoxemia following bilateral sinus nerve block with 2% lidocaine 4 ml. Since EEG was silent while SaO2 was lower than 30%, vigorous CSA at these levels of hypoxemia should be maintained by strong afferent activity of the chemoreceptor site. These combined stimulation of both acute hypoxemia and hypercarbia seem to suggest that CSA response are additive each other. In conclusion, it is indicated that the depressant effects of volatile anesthetics on the CSA responses to acutely induced hypoxemia and hypercarbia can cause depression of the control activity on the autonomic nervous system against hypoxemia and hypercarbia, and conceal the manifestation of clinical signs of hypoxemia and hypercarbia, per se. PMID- 2227792 TI - [Plasma prostaglandin E2 and skin graft rejection in the rat]. AB - The aim of this study is to make it clear whether plasma prostaglandin E2 (PGE2) is a useful parameter or not for prediction and judgement of the graft rejection. We studied the plasma levels of PGE2 in skin graft recipients; a control group of isogeneic grafts with LEW rats, a group of allografts with ACI to LEW and a group of allogeneic graftings with intramuscular administrations of cyclosporin A (CyA) with 20 mg/kg/day from day-2 to day 14. Rejection was judged to be complete when the grafts got dried or appeared graft necrosis. During the first interval after grafting (from 6 hours to the 5th day), significantly high levels of plasma PGE2 with a peak at 12 hours after transplantation (7.8 days prior to 50% skin survival time (ST50), and with 60 times higher value than normal control, can be seen in the allogeneic group. On the other hand, we found no peaks of plasma PGE2 in the immunosuppressed group while using CyA, but a slight elevation was recognized on the 4th day after stopping CyA treatment (7.7 days prior to ST50) with 10 times higher than the normal value. In conclusion, the plasma PGE2 level elevates about 1 week prior to the graft rejection and the serial monitoring may be useful for prediction and judgement of the graft rejection. PMID- 2227793 TI - [DNA sequence analysis of HLA-DQB genes associated with insulin-dependent diabetes mellitus in Japanese]. AB - Recently it has been reported that 57th amino acid of DQ beta antigen was a non aspartic acid in the most Caucasian patients with insulin-dependent diabetes mellitus (IDDM). Using serological analysis, HLA-DQ antigens show a strong association with IDDM rather than the HLA-DR antigens. In the Caucasian population, IDDM is associated with DQw2 and DQw3 antigens. However, in the Japanese population, DQw4 and DQw9 antigens are strongly associated with IDDM. In order to determine the possible significance of the 57th amino acid of DQ beta chain for the susceptibility to IDDM in Japanese, we performed DNA Sequence analysis of HLA-DQB from Japanese IDDM patient, its same HLA genotyped healthy sibling and B cell line with Japanese IDDM associated haplotype. The results revealed that all of the 57th amino acid are aspartic acid which is thought to contribute to develop IDDM resistance in Caucasian. Furthermore we could not find any other amino acid sequence of DQ beta chain which might contribute to the susceptibility of the Japanese IDDM. PMID- 2227794 TI - Estimation of permeability in blood-retinal barrier. AB - Permeability of the blood-retinal barrier (BRB) can be determined by vitreous fluorophotometry and computer analysis. In this study, we characterize our eye model and apply it to normal human subjects. In this investigation of BRB permeability, we employed four parameters for the eye model: the inward permeability (Pin) and outward permeability (Pout) of the BRB; the diffusion coefficient in the posterior vitreous gel (D-p); and the plasma fluorescein concentration. The values of Pin, D-p, and plasma fluorescein concentration significantly affected the fluorescein concentration in the posterior vitreous 60 minutes after intravenous fluorescein injection. The value of Pout had little influence on the fluorescein kinetics in the posterior vitreous 60 minutes after injection. The results of experiments on humans indicate that the estimated values obtained by simulation fit satisfactorily the measured values. It is suggested that our computer simulation method in conjunction with vitreous fluorophotometry can effectively estimate permeability of BRB in normal and pathological eyes. PMID- 2227795 TI - [2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells obtained from patients with chronic hepatitis B during interferon therapy]. AB - The activities of 2',5'-oligoadenylate synthetase (2-5AS) in spleen and liver extracts obtained from mice treated with recombinant mouse interferon-beta (rMuIFN-beta) were investigated. The levels of the enzyme activity increased significantly in both spleen and liver extracts for 72 hours after the treatment with rMuIFN-beta (5 X 10(4)IU). The levels of the enzyme activity in spleen extracts correlated well with those in liver extracts. Therefore it is suggested that the assay of 2-5AS activity in peripheral blood mononuclear cells (PBMC) of patients infected with hepatitis B virus (HBV) is useful for monitoring the antiviral state of liver during IFN therapy. The activities of 2-5AS in PBMC obtained from patients with chronic hepatitis B (CHB) were significantly higher than those of healthy controls, resulting from the endogenous IFNs detected in the patients with CHB. Furthermore, the enzyme activities of PBMC in the patients with CHB increased significantly during IFN therapy as compared with IFN untreated patients. This increase in the enzyme levels during IFN therapy correlated well with the decrease of DNA-polymerase (DNA-P) activities associated with HBV. These results indicate that the assay of 2-5AS detected in PBMC from the patients is valuable to determine the optimal IFN therapy for CHB. PMID- 2227796 TI - Binding of low density lipoprotein (LDL) to C-reactive protein (CRP): a possible binding through apolipoprotein B in LDL at phosphorylcholine-binding site of CRP. AB - Healthy human serum reacted with C-reactive protein of human (hCRP) or rat (rCRP) immobilized on Sepharose 4B in the presence of Ca2+. The bound serum proteins were eluted with 0.1 M ethylenediaminetetraacetic acid, trisodium salt (EDTA) dissolved in 10 mM Tris-HCl buffer, pH 8.0, containing 140 mM NaCl. The eluted proteins from the hCRP column was found to be low density lipoprotein (LDL), 90% of its protein being apo B. The one from the rCRP column contained also apo B by 36.7%. The effect of phosphorylcholine (PC), phosphorylethanolamine, phosphorylserine, galactose and high density lipoprotein (HDL) on the binding of LDL and apo B to CRP was investigated by enzyme-linked immunosorbent assay. Among them, only PC strongly inhibited the binding. One of the two available mouse monoclonal antibodies to hCRP (#19), which interferes with the binding of PC to CRP molecule, prevented CRP from binding LDL or apo B. In contrast, the other antibody (#17), which does not affect the binding of PC to CRP, did not inhibit the binding of LDL or apo B to CRP. It was therefore concluded that LDL binds to CRP by apo B moiety at the PC-binding site of CRP molecule. PMID- 2227797 TI - [A new approach to the quantitative analysis of the vascular architecture and its application to the cerebral cortex of the reeler mouse]. AB - (1) A new method for morphometric studies on the vascular architecture of the mouse brain was developed. The method was as follows: the cerebral vascular images of the arteries, capillaries and veins, which were visualized by injection with gelatinized India-ink, were entirely entered into a personal computer system from a digitizer through light-microscopic photographs (X250). Thus the vessels were transformed into consecutive lines composed of short straight "line segments". The parameters obtained from these "line segments" were the total vascular length per unit area and volume ("length density"), the direction of the "orientation axis" and the "intensity of orientation" of the blood vessels. The three-dimensional properties of the vascular vessels were calculated from these data. The frontal and sagittal vascular patterns of the occipital cortex, thalamus, hippocampus, piriform cortex, internal capsule and corpus callosum were entered and the parameters described above were calculated. The calculated three dimensional "length densities" of the blood vessels in the occipital cortex and thalamus were about twice as great as those of the corpus callosum and internal capsule, and those of the hippocampus and piriform cortex had intermediate values. The "orientation axis" of the occipital cortex was approximately perpendicular to the cerebral surface, while those of the corpus callosum and internal capsule were parallel to the course of the nerve fibers. The axis of the thalamus was parallel to the horizontal plane, and that of the hippocampus was perpendicular to its surface. The "intensity of orientation" of the piriform cortex, however, was very small. (2) In order to investigate the factors defining the vascular pattern in the cerebral cortex, the reeler mutant mouse, in which the lamination of the cortex is reversed and the neurons distributed more homogeneously than in normal mice, was investigated by the above-mentioned method. The vascular pattern of the reeler mutant mouse revealed a difference from that of the normal mouse in that the "length density" of the reeler mouse was apparently equal in different layers, and the degree of vascular orientation was not as intensive as that of the normal cortex, in which the blood vessels tended to be perpendicular to the pial surface.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2227798 TI - [Light microscopic observations on intrapineal neurons and myelinated fibers distributed in the pineal gland and its capsule in cotton rats (Sigmodon hispidus) at various postnatal ages]. AB - From birth to 300 days, neurons are mainly encountered in the distal third of the pineal gland. Neurons are scarce in the middle or proximal third; their number is fewer in the proximal third. Nuclear size of neurons in all pineal regions increases until 100-200 day. Since there are regional differences in size of nuclei of intrapineal neurons in cotton rats until 200 days, intrapineal neurons of this animal may be composed of different populations of cells. The observation that age changes in size of nuclei of intrapineal neurons are similar to those of pinealocytes suggests that such neuronal changes may be related to the functional differentiation of the organ. In all pineal regions, the number of neurons reduces to half from birth to 100 days. The enlargement of neuronal nuclei and the decrease in neuronal numbers proceed simultaneously with advancing age. Half the number of neurons may degenerate and disappear until 100 days. Myelinated fibers in the pineal gland and its capsule appear first at 20 days and their density increases with age. Myelinated fibers are mainly distributed in the distal pineal region and the capsule covering its posteroventral area. Since neurons are mainly located in the posteroventral area of the distal pineal region, a close topographical relation exists between myelinated fibers and intrapineal neurons. The myelinated fibers in the capsule may usually run from distal to proximal regions of the pineal gland; some of these fibers may enter the organ. PMID- 2227799 TI - Spontaneous diabetes in BB rats: evidence for insulin dependent liver microsomal delta 6 and delta 5 desaturase activities. AB - We studied linoleic acid delta 5 and dihomo-gamma-linolenic acid delta 5 desaturations, and fatty acid composition, of liver microsomes in the insulin dependent spontaneously diabetic adult female BB rat. These desaturations were defective along the normo- and hyper-glycemic period and restored during the hypoglycemic period which followed the insulin injection to the diabetic rats. The fatty acid composition of BB rats microsomes was not consistent with the desaturase activities at the different periods of glycemia, probably because other factors than desaturation impairments were involved in the evolution of fatty acid composition. PMID- 2227800 TI - Effect of triiodothyronine and thyroxine on mitochondrial alpha-glycerophosphate dehydrogenase activity and mitochondrial protein content of liver, muscle and brain of toad, Bufo melanostictus. AB - The responsiveness of the adult toad to triiodothyronine (T3) and thyroxine (T4) was studied by measuring the mitochondrial alpha-glycerophosphate dehydrogenase activity and mitochondrial protein content of liver, muscle and brain of toad. Both T3 and T4 increased the alpha-GPD activity and mitochondrial protein content of liver and muscle of toad. The extent of increase in the alpha-GPD activity and mitochondrial protein content were more pronounced with T3 than with T4. Further that the muscle exhibited more alpha-GPD activity than liver, whenever liver showed greater mitochondrial protein content than that of muscle. Brain showed no significant change in the alpha-GPD activity and mitochondrial protein content. Injections of cycloheximide showed inhibition of T3 induced changes in liver and muscle. Injection of propylthiouracil also counteracted the T4 induced effects of liver and muscle. PMID- 2227801 TI - Effects of fetal intravenous glucose challenge in normal and growth retarded fetuses. AB - Fetal intravenous glucose challenge test (0.75 g/kg of estimated fetal weight) was performed at 26-33 weeks gestation in 9 patients undergoing fetal blood sampling (FBS) by ultrasound guided needling from the umbilical vein. The indication for FBS was rapid karyotyping for fetal malformations in 5 (control group) and severe intrauterine growth retardation in the remaining 4 (IUGR group). Fetal blood samples were taken before the glucose infusion and after 1, 3, 5, 10 and 15 min; glucose and insulin were assayed on each occasion and acid base balance at 0 and 5 min. Basal fetal pO2, pH, glucose and insulin were lower in the IUGR group than in controls. Following the glucose challenge, fetal glucose levels were similar in the two groups, but in the IUGR group the latter part of the glucose curve was characterized by a slower and delayed return to basal levels. In control fetuses the insulin response following the glucose challenge peaked at 3 min while in IUGR no change in insulin concentration was detected. Fetal pO2 did not change in either group; the median change in fetal pH was significantly different between the two groups (controls: +0.01; IUGR: -0.04; P less than 0.05) and there was a significant correlation between basal pO2 and the change in fetal pH (r = 0.79) (P less than 0.02). These results support the concept of a low energy state in IUGR. Fetal glucose supplementation in IUGR is unlikely to be of benefit and may even exacerbate underlying acidosis. PMID- 2227802 TI - Effects of low molecular weight peptides and divalent cations on degradation and binding of angiotensin II. AB - The effects of peptide inhibitors (bestatin and amastatin) and divalent cations (Ca2+ and Co2+) on the velocity of Asp1 liberation from angiotensin II (A-II) by human placental membrane fractions and binding of 125I A-II to human placental membranes were tested at 22 degrees C and 4 degrees C. Asp1 liberation was measured by high performance liquid chromatography. As expected, the degradation and binding of A-II were temperature sensitive, with both being at 4 degrees C than at 22 degrees C. While amastatin (10(-4) M) and bestatin 10(-6) M) significantly reduced the velocity of Asp1 liberation from A-II to about 45%, amastatin (10(-4) M) and bestatin (10(-4) M) increased 125I A-II binding to 125% and 130%, respectively. Ca2+ (10 mM) and Co2+ (10 mM) activated the velocity of Asp1 liberation from A-II to 140% and 120%, respectively at 22 degrees C. Ca2+ (10(-1) M) and Co2+ (10 mM) also enhanced 125I A-II binding about 130%. Previously we showed that the A-II degrading activity found in human placental membrane fractions is mainly due to aminopeptidases A and M. Since amastatin and bestatin are the specific inhibitors for aminopeptidases A and M, and since Ca2+ and Co2+ are the activators for aminopeptidase A and aminopeptidase M, respectively, it is conceivable that the enzymes regulate the levels of A-II and, therefore, that they may play an important role in the binding of A-II to human placental membrane fractions. PMID- 2227803 TI - Food intake and diurnal testosterone variation in the Caerphilly Heart Disease Study. PMID- 2227804 TI - Chronic ethanol administration impairs receptor-mediated endocytosis of epidermal growth factor by rat hepatocytes. AB - The effects of chronic ethanol administration on the receptor-mediated endocytosis of epidermal growth factor were studied in isolated rat hepatocytes. In initial experiments, it was demonstrated that significantly less ligand was bound by hepatocytes isolated from rats fed an ethanol liquid diet for 5 to 7 wk than by cells isolated from chow-fed or pair-fed controls. Reduced binding was shown to be primarily caused by a decreased number of surface receptors rather than by changes in receptor affinity. When hepatocytes were incubated at 37 degrees C in the presence of a large saturating concentration of epidermal growth factor (80 nmol/L), intracellular levels of the ligand were significantly lower in cells from the ethanol-fed animals. However, no effect on degradation of the ligand was observed under those conditions. A defect in the initial stages of receptor-ligand internalization was also indicated because less surface-bound ligand was internalized and subsequently degraded in cells from the ethanol treated rats. When the endocytosis of a lower, more physiological concentration of the growth factor (0.5 nmol/L) was studied, both the uptake of ligand and its degradation were markedly impaired in hepatocytes from the ethanol-fed animals. These results indicate that chronic ethanol administration impairs the receptor mediated endocytosis of epidermal growth factor by the liver. The major impairment appears to be a reduction of cell surface receptors; however, other steps of the endocytotic pathway also appear to be affected. These altered steps include defective receptor-ligand internalization and changes in intracellular processing of the ligand leading to decreased degradation. PMID- 2227805 TI - Role of ethanol-inducible cytochrome P-450 IIE1 in carbon tetrachloride-induced damage to centrilobular hepatocytes from ethanol-treated rats. AB - The ethanol-inducible form of cytochrome P-450 (IIE1) is expressed and induced by ethanol, predominantly in the centrilobular region. Because this isoenzyme has a particularly high capacity to convert carbon tetrachloride and several other hepatotoxins into reactive intermediates, its role in producing damage was studied by comparing the effect of carbon tetrachloride exposure on hepatocytes isolated from either the periportal or the perivenous region by digitonin collagenase perfusion. After exposure for 18 hr of primary culture to 600 mumol/L of carbon tetrachloride, periportal cells were only slightly damaged, as estimated from dye exclusion and lactate dehydrogenase leakage. In marked contrast, perivenous cells, which contained a several-fold higher amount of immunoreactive P-450 IIE1 apoprotein, were partly damaged after exposure to 60 to 150 mumol/L of carbon tetrachloride and severely damaged after 600 mumol/L. Similarly, lipid peroxidation after carbon tetrachloride was much more prominent in perivenous cells. The differences between perivenous and periportal cells in carbon tetrachloride-induced injury were larger when cells were isolated from chronically ethanol-treated rats. Isoniazid, an efficient inhibitor of P-450 IIE1, protected against damage by carbon tetrachloride more efficiently than the general P-450 inhibitor cimetidine. Our results suggest that the greater susceptibility of the perivenous hepatocytes to carbon tetrachloride-induced damage is associated with the high expression of P-450 IIE1 in these cells. This enzyme may also be involved in damage elicited by several other typical centrilobular hepatotoxins. PMID- 2227807 TI - Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. AB - Steatohepatitis (fatty liver hepatitis), histologically identical to alcoholic disease, occurs in some obese patients after jejunoileal bypass. A similar lesion occurs rarely in obese patients without bypass surgery, but the risk factors are poorly understood. Hepatic steatosis, steatohepatitis and fibrosis were sought in 351 apparently nonalcoholic patients at autopsy and various risk factors were evaluated. Incidence of steatosis and steatohepatitis correlated with the degree of obesity. Steatohepatitis was found in 18.5% of markedly obese patients and 2.7% of lean patients. Additional risk factors for steatohepatitis were type II diabetes, weight loss in the preterminal period shortly before death and intravenous glucose therapy in the last week of life. Severe fibrosis was found in 13.8% of markedly obese patients and in 6.6% of lean patients; this difference was largely explained by the higher prevalence of diabetes in obese groups. The risk factors defined in this study are known to be associated with abnormalities of free fatty acid metabolism. Obesity, type II diabetes and intravenous glucose therapy are associated with hyperinsulinemia, which may inhibit fatty acid oxidation. Obesity and weight loss increase the presentation of fatty acids to the liver. Similar metabolic changes may occur in obese patients after jejunoileal bypass surgery. Thus this study supports the hypothesis that fatty acids have a role in the hepatocellular necrosis found in some obese individuals. PMID- 2227806 TI - Zonal heterogeneity of the effects of chronic ethanol feeding on hepatic fatty acid metabolism. AB - Periportal and perivenous hepatocytes were isolated from rats fed a high-fat, ethanol-containing diet to investigate the acinar heterogeneity of the effects of prolonged ethanol administration on lipid metabolism. Chronic feeding of ethanol caused a rather selective accumulation of triacylglycerols in the perivenous zone of the liver. In control animals the rate of lipogenesis and the activity of acetyl-CoA carboxylase were higher in perivenous than in periportal hepatocytes, whereas the rate of fatty acid oxidation and the activity of carnitine palmitoyltransferase I were higher in periportal than in perivenous cells; however, no zonation was evident for very-low-density-lipoprotein-lipid secretion. Prolonged ethanol administration abolished the zonal asymmetry of the lipogenic process and inverted the acinar distribution of the fatty acid oxidative process (i.e., in ethanol-fed animals the rate of fatty acid oxidation and the activity of carnitine palmitoyltransferase I were higher in perivenous than in periportal hepatocytes). Moreover, chronic feeding of ethanol led to a marked and selective inhibition of very-low-density-lipoprotein-triacylglycerol secretion by the perivenous zone of the liver. Nevertheless, no zonal differences were observed between control and ethanol-fed animals with respect to the effects of acute doses of ethanol and acetaldehyde on lipid metabolism. In conclusion, our results show that chronic ethanol intake produces important alterations in the acinar distribution of the different fatty acid-metabolizing pathways. PMID- 2227809 TI - Antibodies to nuclear lamin C in chronic hepatitis delta virus infection. AB - Sera of patients with chronic hepatitis delta virus infection stained the nuclear periphery in indirect immunofluorescence. Using proteins of isolated nuclei, isolated nuclear matrices, the nuclear pore complex-lamina fraction and purified lamins A and C as antigen source in immunoblotting experiments, nuclear lamin C was identified as the reactive antigen. Most sera tested (8 of 10) recognized nuclear lamin C exclusively, but not the nuclear lamins A and B. Antibodies reacting with both nuclear lamins A and C, which share extensive sequence homologies, have been reported to occur in autoimmune hepatitis and primary biliary cirrhosis. The present findings suggest that the novel autoantibody associated with chronic hepatitis delta virus infection recognizes an epitope localized in the short carboxyterminal region of nuclear lamin C. PMID- 2227808 TI - Immunization of woodchucks with recombinant hepatitis delta antigen does not protect against hepatitis delta virus infection. AB - To assess the role of immunization against hepatitis delta antigen in the prevention of hepatitis delta virus infection, woodchuck carriers of woodchuck hepatitis virus were immunized with a 64 amino acid portion of hepatitis delta antigen from its N-terminal region. The protein was expressed in Escherichia coli and contained a major immunogenic epitope. A significant anti-hepatitis delta response was observed that did not, however, protect the animals from hepatitis delta virus superinfection. Unexpectedly, the period of detectable viremia was longer in the immunized than in the control animals. We conclude that immunization with this recombinant hepatitis delta antigen does not afford protection against subsequent hepatitis delta virus exposure. PMID- 2227810 TI - Hormonal and enzymatic parameters of hepatic regeneration in patients undergoing major liver resections. AB - Thirteen patients who underwent 40% to 80% removal of their livers had blood samples drawn initially and daily on postoperative days 1 to 7. The enzyme marker of heightened polyamine metabolism, ornithine decarboxylase, and the indicator of DNA synthesis, thymidine kinase, were measured. In addition, the hormones (insulin, glucagon, estradiol and androgen), which in animals are known to reflect and possibly modulate regeneration, were measured. Changes in all these indices followed the same pattern as in rats, dogs and swine but at a slower rate. Ornithine decarboxylase and estradiol increased within 24 hr, but thymidine kinase and insulin rises did not become statistically significant until 3 to 5 days. Using these plasma or serum indices as surrogate measures of biochemical events in the liver itself, regeneration reached a maximum after 4 or 5 days. By computed tomography scan analysis, restoration of hepatic cell mass was not complete until 3 wk. PMID- 2227811 TI - Metabolic actions of insulin-like growth factor-I in cultured hepatocytes from adult rats. AB - Short-term and long-term regulation of hepatic carbohydrate metabolism by insulinlike growth factor-I was studied in primary cultures of adult rat hepatocytes and compared with the metabolic potency of insulin. Insulinlike growth factor-I stimulated the formation of [14C]lactate from [14C]glucose up to three-fold with a half-maximally effective concentration of approximately 50 nmol/L. Basal glycogenolysis was inhibited by about 20%, and glucagon-activated glycogenolysis was blocked completely by insulinlike growth factor-I with half maximally effective concentrations of about 1.5 to 2 nmol/L. The activity of the key glycolytic enzymes glucokinase and pyruvate kinase were induced twofold. The glucagon-dependent induction of phosphoenolpyruvate carboxykinase--the key gluconeogenic enzyme--was antagonized with a half-maximally effective concentration of about 5 nmol/L. This inhibition of the glucagon-dependent induction of the enzyme was accompanied by a similar reduction of the increase in phosphoenolpyruvate carboxykinase-mRNA level as assessed by Northern blot analysis. The potency of insulinlike growth factor-I at half-maximally effective concentrations was approximately 2% to 4% that of insulin. Because binding studies demonstrated a comparably low affinity of insulinlike growth factor-I to the insulin receptor, it is suggested that in adult liver--in contrast to fetal and regenerating liver--insulinlike growth factor-I could exert short-term and long-term metabolic effects on parenchymal cells only through interaction with the insulin receptor. PMID- 2227812 TI - Human hepatic regenerative stimulator substance: partial purification and biological characterization of hepatic stimulator substance from human fetal liver cells. AB - Current support or replacement therapies for fulminant acute hepatic failure are frequently very disappointing. In this study, human hepatic stimulator substance- a liver-specific growth factor--was partially purified from human fetal liver cells and characterized by its biological effects. Almost 70-fold protein content was purified with an approximately 80-fold increase in specific growth stimulator activity. Human hepatic stimulator substance proved to be heat-stable, protease sensitive, organ-specific and species-nonspecific. Human hepatic stimulator substance produced a two- to threefold increase of 3H-thymidine incorporation into hepatic DNA when injected intraperitoneally into growing weanling mice (nonhepatectomized) or regenerating rats (34% hepatectomy). The effects of hHSS in reversing the lethality of D-galactosamine (1.6 gm/kg body weight)-induced hepatic necrosis in rats were further evaluated. A survival rate of 4% (n = 24), 41% (n = 12, p less than 0.05), 33% (n = 12, p less than 0.05), 31% (n = 13, p less than 0.05) and 18% (n = 11, p greater than 0.05) was observed when the rats were injected with 4 ml of saline intraperitoneally, 4 ml of human intact fetal hepatocytes (2.4 x 10(8] intraperitoneally, 4 ml of human hepatic stimulator substance intraperitoneally, 2 ml of twofold concentrated human hepatic stimulator substance intravenously and 1 ml of fourfold human hepatic stimulator substance intramuscularly, respectively, 20 hr after poisoning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227813 TI - Endotoxin and the hyperdynamic circulation of portal vein-ligated rats. AB - Humoral factors may be responsible for the hyperdynamic circulation seen in portal hypertension. Endotoxin, a peripheral arteriolar vasodilator, has been proposed to mediate this hemodynamic picture. We examined the pathogenic role of endotoxin in portal vein-ligated rats, a prehepatic portal hypertensive model with a well-developed hyperdynamic circulation. To this end, we (a) administered oral neomycin, a poorly absorbable antibiotic, at doses of 50 and 100 mg/day for 7 days and found no evident splanchnic hemodynamic effects of a 2-log-fold reduction of cecal aerobic bacterial flora as assessed by the radioactive microsphere technique in portal vein-ligated rats studied in the postanesthesia awake state; (b) assayed endotoxin in arterial samples using a quantitative limulus assay and found no evidence of endotoxinemia in PVL rats; (c) induced a state of endotoxin tolerance by repeated daily intraperitoneal injections of low dose endotoxin and found no amelioration of the hyperdynamic state in portal vein ligated rats. Our results do not support the hypothesis that endotoxin plays a major pathogenic role in the hyperdynamic circulation of this experimental model. PMID- 2227814 TI - A study of the inhibition of adrenaline-induced vasoconstriction in the isolated perfused liver of rabbit. AB - We have studied the action of a series of vasoactive and antispasmodic agents on the intrahepatic vasoconstriction induced by adrenaline in the isolated perfused liver of rabbits. The arterial and portal venous resistance, oxygen consumption, liver weight and bile flow were investigated. The drugs used were as follows: nonspecific alpha-adrenergic antagonists (DH-ergocristine, dibenamine, phenoxybenzamine), vasodilators with a direct miscellaneous action (theophylline, papaverine, dipyridamole, glucagon, Aiu-cor by Instituto Gentilli, Italy [inosine, ATP, IPI, UTP]) and antispasmodics (piperylone, tropenziline, noraminophenazone). Adrenaline increased arterial and portal venous resistance followed by a diminution of oxygen consumption, liver weight and bile flow. alpha Adrenergic antagonists inhibited the effects of adrenaline on portal venous resistance and oxygen consumption and especially the effects on hepatic arterial resistance. The most potent agent was phenoxybenzamine. In contrast to alpha adrenoceptor blockade, the effects of other vasoactive agents were without a sustained influence on hepatic arterial resistance (excepting those of glucagon and dipyridamole). Some of them were effective as antagonists on responses in the portal venous bed (papaverine, Aiu-cor). Moreover, there were drugs exerting an enhancement of the vasoconstrictor responses of hepatic artery to low concentrations of adrenaline with no effect on the portal venous bed (piperylone, tropenziline). Theophylline and noraminophenazone exerted no effect either on the arterial or portal venous bed. No vasodilator agent antagonized the changes of the bile flow after adrenaline administration. PMID- 2227815 TI - Hepatic vascular disease and portal hypertension in polycythemia vera and agnogenic myeloid metaplasia: a clinicopathological study of 145 patients examined at autopsy. AB - The pathogenesis of portal hypertension arising in patients with myeloproliferative disorders has been difficult to understand because liver biopsy findings often show minimal changes. It has been suggested that increased splenic blood flow, hepatic infiltration with hematopoietic cells or sinusoidal fibrosis may be important. We have reviewed the autopsy findings and clinical histories of 97 patients with polycythemia vera and 48 patients with agnogenic myeloid metaplasia collected from three institutions and from the Polycythemia Vera Study Group. Cirrhosis was present in seven patients, one of whom had bleeding varices. Esophageal varices were present clinically in 10 patients without cirrhosis (seven polycythemia and three agnogenic myeloid metaplasia). All of these patients had lesions in small or medium-sized portal veins and four had stenosis of the extrahepatic portal vein with histology compatible with organized thrombi. Nodular regenerative hyperplasia occurred in 14.6% and correlated closely with the presence of portal vein lesions. Thirty patients had greater than 500 ml of ascites, seven of these patients also had varices and six of them had hepatic vein thrombosis. Ascites also correlated with hepatic vein disease confined to small intrahepatic branches. No correlation was seen between hepatic hematopoietic infiltration and signs of portal hypertension. We conclude that esophageal varices are common and are almost always associated with portal vein lesions visible by light microscopy. These portal vein lesions, and the secondary effects of nodular regenerative hyperplasia and portal hypertension, are most likely a result of portal vein thrombosis in patients with myeloproliferative disorders. PMID- 2227816 TI - Selective intestinal decontamination increases serum and ascitic fluid C3 levels in cirrhosis. AB - Selective intestinal decontamination for 7 days with norfloxacin was performed in 14 cirrhotic patients with ascites and low ascitic fluid total protein. Variations in serum and ascitic fluid of C3 and C4 and ascitic fluid total protein after therapy were compared with those of a control group of 14 untreated patients with similar characteristics. After oral norfloxacin administration, we saw a significant increase of C3 in serum (p less than 0.05) and ascitic fluid (p = 0.01). A significant increase was also observed in ascitic fluid total protein (p less than 0.05) but not in serum and ascitic fluid C4. There were no changes in serum C3, ascitic fluid C3, ascitic fluid C4 or in ascitic fluid total protein in group 2. These data demonstrate that selective intestinal decontamination increases serum and ascitic fluid C3 levels and, therefore, might be useful in preventing spontaneous infections in cirrhotic patients at high risk of infection. PMID- 2227817 TI - Involvement of tumor necrosis factor-alpha in development of hepatic injury in galactosamine-sensitized mice. AB - Intravenous injection of lipopolysaccharide and D-galactosamine, at doses of 0.2 micrograms/kg and 800 mg/kg, respectively, elicited massive hepatic necrosis within 24 hr in C3H/HeN mice. The plasma L-alanine aminotransferase (ALT, E.C. 2.6.1.2) or L-aspartate aminotransferase (AST, E.C. 2.6.1.1) activities at this point reached more than 2,000 IU/L. However, overt hepatic injury as evaluated by the plasma aminotransferase activities did not develop in mice in which only lipopolysaccharide or only D-galactosamine was injected. No tumor necrosis factor like activities could be detected in the plasma of galactosamine- and lipopolysaccharide-injected mice as determined by the assay of cytotoxicity to highly tumor necrosis factor-sensitive L-P3 cells through the experimental period of 24 hr. However, passive immunization against mouse tumor necrosis factor-alpha with polyvalent rabbit anti-mouse tumor necrosis factor-alpha antiserum, which was able to neutralize the cytotoxic effects of recombinant mouse tumor necrosis factor-alpha on L-P3 cells, could protect the mice from the development of hepatic injury in a dose-dependent manner. Simultaneous injection of recombinant human tumor necrosis factor-alpha, instead of lipopolysaccharide, with 800 mg/kg of D-galactosamine in lipopolysaccharide-resistant C3H/HeJ mice sensitized the animals more than one thousand-fold to the development of hepatic injury. The livers appeared to be morphologically similar to those of galactosamine- and lipopolysaccharide-injected C3H/HeN mice. PMID- 2227818 TI - Calcium absorption in bone disease associated with chronic cholestasis during childhood. AB - Fractional absorption of calcium was determined in 9 children aged 4.9 to 16.9 yr with chronic cholestatic liver disease to determine the role of calcium malabsorption in the development of metabolic bone disease. Radiological evidence of rickets was absent in all patients, but bone density, measured by single beam photon absorptiometry of the distal radius, was reduced in eight of nine subjects. Serum calcium and phosphorus concentrations were normal in all except one subject. Serum 25-hydroxyvitamin D concentration was decreased compared with controls in only one of nine patients, but serum 1,25-dihydroxyvitamin D concentrations were diminished in seven of nine subjects. In all subjects, dietary calcium and phosphorus intakes were greater than 80% of the RDA. Fractional absorption of calcium, determined by oral and intravenous administration of stable calcium isotopes, was similar in cholestatic compared with control subjects (37.1% +/- 12.5% vs. 34.0% +/- 16.4%). In the cholestatic subjects, calcium absorption correlated with serum 1,25-dihydroxyvitamin D (r = 0.871, p less than 0.002) but not 25-hydroxyvitamin D concentrations. Calcium balance, assessed by the duplicate diet method, was positive in four of five subjects. Anthropometric measurements were performed to examine the relationship between nutritional status and bone mineral content. Heights of all subjects were less than or equal to the 10th percentile and fat stores and somatic protein stores were less than the 25th percentile in six of nine subjects. We conclude that factors other than calcium malabsorption and decreased serum 25 hydroxyvitamin D concentration contribute to diminished bone mass in children with cholestatic liver disease. PMID- 2227819 TI - Effect of chronic administration of ursodeoxycholic acid on the ileal absorption of endogenous bile acids in man. AB - The effect of long-term administration of ursodeoxycholic acid on the ileal absorption of endogenous bile acids was determined using the tauro 23 (75Se) selena-25 homotaurocholic acid test in a controlled double-blind study involving healthy subjects (n = 15). Subjects received placebo or 13 to 15 mg/kg/day ursodeoxycholic acid for 5 wk. In the placebo group (n = 7) there was no change in the composition of serum bile acids or in the mean percentage of retention of tauro 23(75Se) selena-25 homotaurocholic acid (36.1% +/- 6.0% vs. 38.7% +/- 6.7%). In contrast, in the ursodeoxycholic acid group, serum ursodeoxycholic acid conjugates increased and the percentage of retention of tauro 23 (75Se) selena-25 homotaurocholic acid fell from 45.8% +/- 6.8% to 20.5% +/- 5.7% (p less than 0.01). We conclude that ursodeoxycholic acid administration reduces ileal absorption of endogenous bile acids. These findings provide a rational explanation for the changes in the composition of the bile acid pool during ursodeoxycholic acid therapy and could have important therapeutic implications. PMID- 2227820 TI - Bile acids exert negative feedback control on bile acid synthesis in cultured pig hepatocytes by suppression of cholesterol 7 alpha-hydroxylase activity. AB - Feedback regulation of bile acid synthesis by its end products was studied in cultured hepatocytes of young weaned pigs. We previously showed that conversion of exogenous [14C] cholesterol into bile acids was suppressed by addition of bile acids to the culture medium. In the present study, the effects of bile acids on bile acid mass production and cholesterol 7 alpha-hydroxylase activity were examined. Mass production of bile acids was strongly inhibited by addition of taurocholic acid (50 and 100 mumol/L) to the culture medium. The inhibitory action was exerted specifically on activity of cholesterol 7 alpha-hydroxylase because conversion of [14C] 7 alpha-hydroxycholesterol to bile acids by pig hepatocytes was not affected. Suppression of cholesterol 7 alpha-hydroxylase activity after incubation of the hepatocytes with taurocholic acid was concentration- and time-dependent. Maximum suppression (-80%) was achieved after a 20 to 30 hr incubation of hepatocytes with 100 mumol/L of this bile acid. Decline of enzyme activity caused by 100 mumol/L taurocholic acid followed first order kinetics with a half-life of 10 hr. Taurocholic acid had no direct effect on cholesterol 7 alpha-hydroxylase activity in homogenates of hepatocytes as assessed by addition of the bile acid to the assay mixture. The effects of several other bile acids in a concentration of 100 mumol/L on cholesterol 7 alpha hydroxylase activity were examined in 48 hr incubations. Glycochenodeoxycholic and glycohyodeoxycholic acids, which are the major bile acids in pig bile, their unconjugated forms and also deoxycholic and cholic acid pronouncedly inhibited activity of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227821 TI - Hepatic injury induced by bile salts: correlation between biochemical and morphological events. AB - Continuous intravenous infusion of taurochenodeoxycholate at a rate of 0.4 mumol.min-1.100 gm-1 for only 30 min in rats caused threefold to tenfold greater release of proteins (alkaline phosphatase, lactate dehydrogenase and albumin) into bile in comparison with animals infused with tauroursodeoxycholate at much higher rates (1.8 mumol.min-1.100 gm-1) for 2 hr. The simultaneous infusion of tauroursodeoxycholate and taurochenodeoxycholate (0.6 and 0.4 mumol.min-1.100 gm 1, respectively) for 2 hr prevented the marked biochemical changes in the bile induced by taurochenodeoxycholate for 15 to 60 min exhibited significantly more necrotic hepatocytes, especially in zone 1, in comparison with animals infused with tauroursodeoxycholate or a combination of taurochenodeoxycholate and tauroursodeoxycholate. A good correlation was observed between biochemical and morphological indices of bile acid-induced hepatocyte injury. These data suggest that (a) primary events induced by the acute infusion of toxic bile salts responsible for cholestasis include zone 1 hepatocellular necrosis and (b) this can be prevented by the simultaneous infusion of tauroursodeoxycholate. PMID- 2227822 TI - Characteristics of biliary lipid metabolism after liver transplantation. AB - Biliary lipid metabolism was studied after 10 liver transplantations with continuous drainage of bile. Within 3 wk after transplantation, the new liver produced bile with concentrations of biliary lipids in agreement with those reported for T-tube bile in cholecystectolized nontransplanted subjects. Although changes in biliary lipid composition occurred swiftly in response to various forms of disturbed liver function, they did not provide substantially more information than did standard serum tests or simple measurements of bile flow in most patients. Secretion rates of phospholipids and cholesterol were found to be completely bile acid dependent. For each micromole of bile acids, 0.22 and 0.08 mumol of phospholipids and cholesterol were secreted, respectively. When bile flow was related to bile acid output, a linear relationship was found (r = 0.89), with a positive intercept indicating a bile acid-independent bile flow of approximately 44 microliters/min. Analysis of individual bile acids showed almost exclusively primary bile acids. The relative proportion of chenodeoxycholic acid was more prominent during the first days after transplantation. Different explanations for this are discussed. PMID- 2227824 TI - 31Phosphorus nuclear magnetic resonance spectroscopy: what does it tell us about alcohol-induced liver disease? PMID- 2227823 TI - Perspectives on Wilson's disease. PMID- 2227825 TI - Mechanism of cholate uptake: Na(+)-cotransport, but not cholate/OH- exchange. PMID- 2227826 TI - Effect of lactulose on the metabolism of short-chain fatty acids. PMID- 2227828 TI - Decrease of growth hormone binding in hepatomas. PMID- 2227827 TI - Alcohol content of various beverages: all booze is created equal. PMID- 2227829 TI - Chronic hepatitis in liver allografts. PMID- 2227830 TI - Current problems in the pathology of intra-epithelial lesions of the uterine cervix. AB - Problems in the interpretation and diagnosis of intraepithelial lesions of the uterine cervix include interobserver differences in respect of grading, uncertainty as to the significance of human papillomavirus infection and debate about the current terminology. The role of human papillomaviruses in cervical intra-epithelial neoplasia (CIN) remains unclear and the specific type of virus present does not correlate closely with the behaviour of these lesions. There are defects in the current terminology and in proposed new terminology for CIN; it is suggested that the term 'borderline CIN' should be introduced in cases where there is uncertainty as to whether or not CIN 1 is superimposed on a flat condyloma. PMID- 2227831 TI - An immunohistological study of condylomata acuminata. AB - Using an indirect immunoperoxidase method and a panel of monoclonal antibodies, anogenital warts removed from 86 individuals (28 heterosexual men, 47 homosexual men and 11 women) were studied. A constant feature was the presence of a stromal infiltrate of lymphocytes, in which CD4+ and CD8+ cells appeared in a ratio of about 5:1. Cells expressing interleukin-2 receptors were found in the stroma, amounting to 10% of the CD3+ cells. Leu 6+ epidermal dendritic cells (Langerhans' cells) were present in each wart; their density and morphology were similar to that in adjacent, apparently normal, skin. The mean number of Langerhans' cells that expressed HLA-DQ was lower than that of HLA-DR + cells. In 40 warts, HLA-DR was expressed on the surface of keratinocytes. Leu 7+ and Leu 11b+ cells were found in the epidermis of 17 and five warts, respectively. B-cells were noted in only five warts. These results are discussed in relation to persistence of wart virus infection. PMID- 2227832 TI - A combination of cytological and architectural morphometry in assessing regenerative hyperplasia and dysplasia in ulcerative colitis. AB - Morphometry and stereology were used to assess the cytological and architectural characteristics of regenerative and dysplastic colorectal mucosal abnormalities in ulcerative colitis. Reproducibility of measurements was assessed and found to be good, confirming the objective and reproducible nature of morphometric analysis. Discriminant analysis between the morphometric features of regenerative mucosal change and low-grade dysplasia revealed the significant cytological and architectural variables from which a cytological and architectural score were derived. The architectural score was capable of classifying all of the cases into their correct diagnostic category, although a combination of the two scores provided better separation of cases. Probability density analysis was carried out so that probabilities of group membership could be allocated to cases, given their cytological and architectural scores. Discriminant analysis was also applied to low- and high-grade dysplasia. Important cytological and architectural variables were identified and used separately to derive scoring systems. In combination, the dual scoring of lesions was capable of separating low- from high grade dysplasia, although overlap was still evident. Again, probability density analysis allowed the allocation of cases into one or other category, although a closer examination showed that such a rule could not successfully classify a new set of low- and high-grade dysplasia cases. Quantitative histological analysis of mucosal abnormalities is shown to be of use in the objective diagnosis of reactive and dysplastic change in patients with ulcerative colitis. The use of simple scoring systems and probability based allocation of cases promotes the future role of morphometric techniques in the diagnostic laboratory. PMID- 2227833 TI - Immunoproliferative small intestinal disease: a study of 13 cases with alpha heavy-chain disease. AB - The pathology of 13 cases of immunoproliferative small intestinal disease (IPSID) associated with alpha-heavy-chain disease--one an apparent non-secretor and another with localized infiltration--is described. Four cases exhibited immunohistological light-chain monotypia. In one of these, evolution of a light chain negative cell population was observed over a 7-year period. In the intestine, centrocyte-like cells produced lympho-epithelial lesions in 11 cases and enlarged lymphoid follicles in three. In lymph nodes, perifollicular infiltration was observed in 11 cases and abnormal follicles in six. Of three patients with high-grade lymphoma at presentation, one died untreated at 2 months, and two are alive at 34 and 91 months. Of 10 patients with low-grade disease at presentation, two died--one at 76 months, the other after transforming to high-grade lymphoma at 73 months. Eight patients with low-grade disease are alive, an average of 67 months after presentation. Four of five conservatively treated low-grade cases (including three in remission) showed evidence of monoclonality at presentation (light-chain monotypia in two and gene rearrangement in two), while two of the five exhibited DNA aneuploidy. It is concluded that IPSID with alpha-heavy-chain disease is neoplastic in all its stages and is a variant of mucosa-associated lymphoma. The role of centrocyte like cells and the response to conservative therapy are discussed. PMID- 2227834 TI - Gastric lymphoma associated with mucosal and nodal granulomas: a new differential diagnosis in granulomatous gastritis. PMID- 2227835 TI - Intramammary tuberculous lymphadenitis. PMID- 2227836 TI - Combined immunohistochemical study of tissue polypeptide antigen and cancer antigen 125 in human ovarian tumours. AB - An indirect immunoperoxidase method was used to study the expression of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA 125) in 47 benign and malignant ovarian tumours. Tissue polypeptide antigen and CA 125 antigen were expressed respectively in 22 (73%) and 16 (53%) of the 30 adenocarcinomas and in five (29%) and four (23%) of the 17 benign tumours. Co-expression of TPA and CA 125 antigen occurred in 12 (40%) malignant and four (23%) benign tumours. Ultrastructurally, TPA and CA 125 antigens were located at the cell surface and microvillous surfaces. Evaluation of combined TPA and CA 125 antigen results revealed a remarkable improvement in the positivity rate and a significant decrease (P less than 0.05) in the negativity rate of ovarian carcinomas as compared with the result of each one separately. These findings provide complementary evidence for the previous results on the plasma levels of TPA and CA 125 antigen and suggest that specific combinations of tumour markers may be more effective for the diagnosis and monitoring of ovarian carcinomas, than the use of any single marker. PMID- 2227837 TI - 'Diamond-shaped' crypts and mucosal elastin: helpful diagnostic features in biopsies of rectal prolapse. AB - The biopsy diagnosis of prolapsing rectal mucosa syndrome can be difficult. We present two newly described features--'diamond-shaped' crypts and mucosal elastin -which appear to be helpful in histological diagnosis. Of 32 biopsies of prolapsing rectal mucosa syndrome, all showed diamond-shaped crypts or mucosal elastin, and 28 contained both. Control biopsies comprised cases of normal or irritable bowel syndrome (46), irradiation colitis and ischaemic colitis (16), inflammatory bowel disease (26), and adenomas (30). Mucosal elastin and 'diamond shaped' crypts with distinctive scalloped edges, which were never seen in prolapse, were observed in half the cases of irradiation and ischaemic colitis. Diamond-shaped crypts were seen in one case of inflammatory bowel disease. Diamond-shaped crypts and elastin were seen in the base of adenomas large enough to cause localized prolapse, and in four biopsies from patients with irritable bowel syndrome, all of whom had given a history of straining at stool. PMID- 2227839 TI - An aggressive lipoblastic tumour in the orbit of a child. AB - The case is described of a locally aggressive lipoblastic tumour presenting in the orbit of an 8-year-old boy. There do not appear to be any previous reports of a comparable tumour in this situation. PMID- 2227838 TI - Multicentric Castleman's disease in association with a solitary plasmacytoma: a case report. AB - Multicentric Castleman's disease with aggressive systemic symptomatology is usually associated with the plasma cell variant. We report a case in which the clinical presentation was typical of multicentric Castleman's disease but which was associated with the hyaline vascular subtype histologically. Plasma cells were absent from all biopsies until, at autopsy, a solitary plasmacytoma was found in the vertebral column. This case supports the view that plasma cells are of primary importance in the clinical and pathological manifestations of multicentric Castleman's disease. PMID- 2227840 TI - Cystadenocarcinoma of the appendix testis. AB - We report an example of what we believe to be an adenocarcinoma of the appendix testis. This very rare neoplasm arose in a patient on long term treatment with oestrogens which may be implicated as an aetiological factor. PMID- 2227841 TI - Bilateral virilizing sclerosing stromal tumours of the ovary in a pregnant woman with Gorlin's syndrome: implications for pathogenesis of ovarian stromal neoplasms. AB - A woman with Gorlin's syndrome who had become pregnant following clomiphene therapy presented in early pregnancy with bilateral ovarian sclerosing stromal tumours which were associated with profound virilization. Pre- and post-operative hormone profiles indicated androgen production by the tumours. Ovarian sclerosing stromal tumours have not previously been reported as occurring bilaterally or in association with Gorlin's syndrome. We discuss the questions raised by this unusual case regarding the pathogenesis of ovarian stromal neoplasms. PMID- 2227842 TI - Plasmacellular Castleman's disease and POEMS syndrome. PMID- 2227843 TI - Squamous cell carcinoma arising in a chronic hydrocoele. PMID- 2227844 TI - Plexogenic pulmonary arteriopathy. PMID- 2227845 TI - Facilitation of receptive behavior in estrogen-primed female rats by the anti progestin, RU 486. AB - The progestin receptor antagonist RU 38486 (henceforth referred to as RU 486) was tested for facilitative effects on female receptive behavior in ovariectomized Long-Evans rats primed with 2 micrograms estradiol benzoate (EB). RU 486 (0, 0.5, 1.6, or 5.0 mg) was administered 48 hr after estrogen priming. The lordosis quotient (LQ) and lordosis score (LS) were assessed 4 hr after RU 486 administration in a standardized test consisting of a 10-mount test by a stimulus male. A significant dose effect was found by both LQ and LS, with those subjects receiving 5 mg of RU 486 being significantly more receptive than vehicle control animals. Thus RU 486 acted as a weak progestin agonist under testing conditions typical for assessment of progestin facilitation of female sexual behavior in rats. Low levels of proceptive behavior (hops and darts) were seen in a minority of the tests, and did not vary systematically as a function of the dose of RU 486 administered. We also examined the effects of RU 486 given before progesterone (P) on receptivity in a blocking paradigm and confirmed previous reports that the antagonist significantly attenuates facilitation of sexual behavior when given in combination with P. A progestin receptor assay of the cytosols of the hypothalamus-preoptic area in estrogen-primed female rats treated with 5 mg RU 486 revealed a significantly greater depletion of available cytosolic P receptors than when rats were treated with a similarly facilitating dose of P (100 micrograms). The results suggest a possible dual mode of action for RU 486--a weak, receptor-mediated agonistic effect on sexual behavior when given alone to estrogen-primed rats, and a competitive blocking effect on receptivity when administered with P. PMID- 2227846 TI - Gonadal hormones during puberty organize environment-related social interaction in the male rat. AB - This study examined the role of gonadal androgens during puberty on the development of environment-related social interaction (SI) in male rats. SI in an unfamiliar environment versus SI in a familiar environment was evaluated in young adult rats as a function of sex and gonadal status. Intact male rats at 60 days of age exhibited a differential response to the two environments, whereas SI in intact female rats at 60 days was equivalent in the two environments. Furthermore, male rats castrated as juveniles and tested for SI at 60 days displayed a pattern of environment-related SI similar to SI in intact adult female rats. This effect of juvenile castration on SI in male rats was prevented by chronic exposure to testosterone propionate (TP) over Days 30 through 60. SI in male rats castrated in adulthood, on the other hand, was not altered either 2 or 4 weeks postcastration. The results from this study indicate that pubertal secretions of gonadal androgen(s) are necessary for the development of environment-related SI in male rats. In contrast, secretions of gonadal androgens in adulthood do not appear to be critical for the continued expression of environment-related SI, as suggested by the observation that environment-related SI in male rats remains unchanged by castration in adulthood. PMID- 2227847 TI - Effects of restraint stress on plasma LH and testosterone concentrations, Leydig cell LH/hCG receptors, and in vitro testicular steroidogenesis in adult rats. AB - We examined the effect of restraint stress (3 hr) on plasma LH and testosterone levels, on the Leydig cell LH/hCG receptor, and on the activity of enzymes in the testicular steroidogenic pathway of the adult rat. Restraint stress caused a 47% reduction in plasma testosterone concentrations, but had no effect on plasma LH levels. The binding capacity and affinity of Leydig cell LH/hCG receptors were not affected by restraint. Stress did not affect the testicular activity of 20,22 desmolase or 3 beta-hydroxysteroid dehydrogenase, but testicular interstitial cells of stressed rats incubated in vitro with progesterone as a substrate produced more 17 alpha-hydroxyprogesterone but less testosterone than control cells, and when incubated with 17 alpha-hydroxypregnenolone, produced 39% less androstenedione and 40% less testosterone than control cells. These results suggest that restraint stress inhibited 17,20 desmolase but not 17 alpha hydroxylase activity. When the delta 4 pathway was blocked with cyanoketone (3 beta-HSD inhibitor), stress did not alter the production of pregnenolone or 17 alpha-hydroxypregnenolone, but the production of dehydroepiandrosterone by cells from stressed rats was subnormal, suggesting again a reduction of 17,20 desmolase activity. The data suggest that a major site of the inhibitory action of restraint stress on testicular steroidogenesis is the 17,20 desmolase step. The disruption of androgen production by restraint appears to be LH independent since stress did not affect plasma LH levels, the binding capacity or affinity of LH/hCG receptors, or the activity of 20,22 desmolase. PMID- 2227848 TI - Prolonged estrogen-progesterone treatment of nonpregnant ovariectomized rats: factors stimulating home-cage and maternal aggression and short-latency maternal behavior. AB - A 16-day treatment of nonpregnant, ovariectomized rats using 5-mm Silastic implants of estradiol (E), daily injections of 4 mg of progesterone (P), and terminal injections of 5 micrograms/kg of estradiol benzoate (EB) to provide a pregnancy-like pattern of hormone exposure, stimulates (a) home-cage aggression toward unfamiliar intruder rats, (b) short-latency maternal behavior when the females are exposed continuously to pups, and (c) maternal aggression after maternal care has been initiated. Preliminary experiments examined the persistence of stimulation of aggression by the 16-day treatment in the absence of exposure to pups eliciting maternal care, and whether an abbreviated, 1-week treatment stimulates aggression equally. Subsequent experiments examined the importance of the elements of the treatment (E implants, P injections, EB injection), and whether prolonging exposure to P or E would alter its behavioral effects. The full 16-day E/P/EB treatment stimulated higher levels of home-cage and maternal aggression, and shorter maternal behavior latencies than abbreviated and partial treatments. E in combination with P or EB significantly raised home cage aggression, whereas P alone was without effect. Administering P for 2 additional days attenuated reductions in maternal behavior latencies by E/P/EB, but did not reduce home-cage or maternal aggressiveness. Continuous exposure to E throughout testing did not affect any dependent variable. Comparing these findings to earlier data and reports suggests that hormone exposure for 2 weeks or more, and provision of P levels approaching those of pregnancy are important to the effects of the E/P/EB treatment on aggression. PMID- 2227849 TI - Oxytocin inhibits infanticide in female house mice (Mus domesticus). AB - Between 60 and 90% of female house mice spontaneously kill unrelated young. A previous report indicated that subcutaneous administration of oxytocin significantly reduced the frequency of infanticide by virgin and pregnant females. However, in this study a distinction could not be made between an action of oxytocin on the CNS versus a secondary effect such as an enhanced release of prolactin by oxytocin. In the current experiment, oxytocin administered intracerebroventricularly was equally as effective at inhibiting infanticide as sc oxytocin. There was no difference in the effectiveness of oxytocin between groups of infanticidal females that were gonadally intact, ovariectomized, or estrogen treated. Pretreatment of infanticidal females with the prolactin inhibitors, bromocriptine and cysteamine, was also without effect on the ability of oxytocin to inhibit infanticide. Last, prolactin-inhibiting drugs had no significant effect on spontaneous parenting behavior by female mice. These data suggest that oxytocin acts directly on the CNS to alter behavior toward pups and that prolactin may not play a role in the maternal behavior of the house mouse. PMID- 2227850 TI - Effects of estrogen treatment on dominance relationships in cows. AB - The effects of prolonged estrogen treatment were studied in two groups of eight ovariectomized heifers. In Group I, four animals were treated with increasing doses of estradiol benzoate (300 micrograms/day to 1.5 mg/day) for 180 days. In Group II, four animals were treated with 1.5 mg/day for 90 days. In each group the other four animals received the vehicle only. Ninety percent of the dominance relationships between treated and control animals was reversed. The delay was, nevertheless, longer than those observed previously following androgen treatment. As is the case following androgen treatment, changes in social rank could not be explained by an increase in aggressiveness by treated animals, but rather could be explained by a lowered reactivity to aggressions and perhaps by a decrease in fear reactions. PMID- 2227851 TI - Testosterone and sexual behavior in oral contraceptive users and nonusers: a prospective study. AB - The relationship between plasma testosterone (T) secretion and patterns of sexual behavior was examined in 18 women using oral contraceptives (OCs) and 13 nonusers matched for partner availability. Retrospective assessments of perimenstrual symptoms, sexual attitudes, and sexual experience were obtained and women completed daily ratings of the frequency of sexual activities and the level of well-being for 1 month. Plasma levels of sex hormone binding globulin (SHBG), progesterone, Total T, Free T, and non-SHBG bound T were determined by radioimmunoassay at four phases of the pill or menstrual cycle. Overall, women not using OCs had higher plasma levels of Total, Free, and non-SHBG bound T and lower plasma levels of SHBG than those of OC users. Further, only nonusers had perimenstrual decreases in plasma levels of Total and Free T. The two groups were comparable on most retrospective measures. However, OC users reported more satisfaction with their sexual partners than did nonusers and prospective monitoring revealed that they engaged in sexual interactions more frequently than did nonusers across the cycle. In contrast, both groups reported a similar frequency of autosexual activities across the cycle. There were no correlations between average levels of T and levels of sexual desire, sexual interactions, or autosexuality. Moreover, only nonusers reported a decrease in levels of sexual desire during the perimenstrual period that was associated with the changes in Free T over the menstrual cycle. PMID- 2227852 TI - Sex differences in the play behavior of immature spotted hyenas, Crocuta crocuta. AB - Social, locomotor, and object play were studied in a colony of five male and five female peer-reared spotted hyenas during 12 1-hr tests while the animals were 13 19 months of age. Animals were tested in both same-sex and mixed-sex groups and were stimulated to play by the introduction of fresh straw and sawdust bedding. Each test was videotaped and the frequency of each type of play was determined by a time sampling procedure. Females played more frequently than males, however, the category of play which was elevated depended upon the social context during testing. In same-sex tests the frequency of vigorous social play displayed by females markedly exceeded that by males, but no comparable sex difference appeared in mixed-sex tests. Females engaged in locomotor play more frequently than males in mixed-sex tests, but no comparable sex difference appeared in same sex tests. No sex difference in object play was observed. Two male and two female hyenas were gonadectomized prior to the initiation of the present sequence of tests. The results suggest that gonadectomy during the prepubertal period does not affect the frequency of play behavior. However, the small sample sizes preclude any conclusive determination of the effects of these gonadectomies on play. PMID- 2227853 TI - Role of septum and preoptic area in regulating masculine and feminine sexual behavior in male rats. AB - The effects of septal or preoptic lesions on both masculine and feminine sexual behaviors were examined in castrated adult male rats. Three weeks after brain surgery, animals were implanted with Silastic tubes containing testosterone (T) and observations of masculine sexual behavior were carried out four times every 5 days. T tubes were removed immediately after the end of the masculine behavioral tests. Two weeks later, animals implanted with Silastic tubes containing estradiol-17 beta(E2) were subjected to three feminine sexual behavioral tests at 5-day intervals. The bilateral lateral septal lesion (LSL) and the medial preoptic lesion (MPOL) effectively suppressed the performance of mounts, intromissions, and ejaculations, whereas the medial septal lesion (MSL), the dorsolateral preoptic lesion (DPOL), and the sham operation did not show any significant suppression of these behaviors. In the feminine sexual behavioral tests, intact and sham-operated control males showed only a low lordotic activity. However, the performance of the lordosis reflex was markedly facilitated by LSL or DPOL, while the lordotic activity of MSL and MPOL males was not significantly different from that of control males. These results suggest that the lateral septum exerts not only a facilitatory influence on masculine sexual behavior but also an inhibitory influence on feminine sexual behavior in male rats. On the other hand, the medial preoptic area may play a critical role in regulating masculine sexual behavior in male rats. PMID- 2227854 TI - The effects of testosterone administration and visual erotic stimuli on nocturnal penile tumescence in normal men. AB - Nocturnal penile tumescence (NPT), as circumference change and rigidity, and REM sleep were measured in eight normal eugonadal men in two controlled experiments. In the first, exposure to erotic film prior to sleep had no effect on frequency of REM or on NPT. In the second placebo controlled experiment 150 mg im testosterone enanthate administration was associated with enhanced rigidity of NPT but with no effect on frequency or circumference change of NPT and no effect on frequency of REM. PMID- 2227855 TI - How hospital CEOs plan to control costs. PMID- 2227856 TI - Not-for-profit hospitals fight tax-exempt challenges. AB - The message being sent by local tax boards, state agencies, and the Internal Revenue Service is clear: Not-for-profit hospitals will have to justify their tax exempt status. But complying with this demand can be a costly administrative burden. Just ask the executives who have been through the experience. CEO Richard Anderson, of St. Luke's Hospital, Bethlehem, PA, is luckier than some executives who have faced tax-exempt challenges. He won his hospital's case. But he still faces a yearly battle: The hospital must prove its compliance annually to the county board of assessors. Other executives report similar experiences. Our cover story takes an in-depth look at how administrators faced challenges to their hospital's tax status and what they learned about their relationship with their communities, as well as a complete state and federal legislative outlook for future developments. PMID- 2227857 TI - Congress measures hospitals' community benefit. PMID- 2227858 TI - The IRS is set to turn up the heat on not-for-profits. PMID- 2227859 TI - Survey lets physicians diagnose deficits in hospital operations. PMID- 2227860 TI - Catholic hospitals join forces with non-Catholic competitors. AB - Many Catholic hospitals are teaming up with nearby non-Catholic providers to develop stronger regional systems of care. Like all collaboration arrangements, these deals must survive state regulatory scrutiny as well as monitoring for antitrust violations by federal agencies. Unlike other arrangements, however, religious and philosophical issues must also be reconciled. PMID- 2227861 TI - Effective employee surveys require commitment to change. AB - Some hospital administrators have turned to employee opinion surveys for guidance on employee relations. That's because there is an emerging consensus that employee opinion surveys can help hospitals stay competitive. Yet up to now, the hospital field's record for making use of such surveys is poor, say organizational development specialists. PMID- 2227862 TI - Occupational health programs reap profits and referrals. AB - Hospitals with occupational health programs can build profitable bridges with employers. Programs that offer comprehensive, client-driven services are most likely to succeed, experts say. PMID- 2227863 TI - Overcoming MD resistance to occupational programs. PMID- 2227864 TI - As cardiology market matures, technology's impact is clearer. AB - What's the likelihood that magnetic resonance imaging will become a more important diagnostic tool for cardiologists? Are electrophysiology services the "wave of the future" in cardiology? These were among several issues discussed at a recent conference on cardiac services. PMID- 2227865 TI - CEO ups admissions by making hospital physician-friendly. PMID- 2227866 TI - Nurse attorneys can educate lawmakers, attorney says. PMID- 2227867 TI - Behavior is the most effective communicator. AB - Actions speak louder than words. This is one of the most important strategies for successful organizational communications. Managers can best communicate their organization's vision, values, and concern for customers and employees through their own behavior. PMID- 2227869 TI - Exclusive physician contracts can be a win/win situation. PMID- 2227868 TI - Employees key to hospitals' future survival. AB - Hospitals that don't invest in their employees may be endangering their own survival, hospital CEOs say. Almost 87 percent of 250 hospital CEOs recently polled by Hospitals magazine say that the declining skill level of workers will adversely affect quality of care. PMID- 2227870 TI - Hospitals provide written payment policies for patients. PMID- 2227871 TI - Quality is not a problem for CA recovery centers. PMID- 2227872 TI - CEOs who negotiate get top retirement plans. PMID- 2227873 TI - Cancer patients fly with 'corporate angels'. PMID- 2227874 TI - What consumers look for in an internist. AB - Consumers are looking for a high level of physician/patient interaction with their internists regarding treatment options, but their demand for extended appointment hours varies widely by location. Look to Data Watch for insights into what will attract consumers to members of your medical staff. PMID- 2227875 TI - Imaging. AB - Medical imaging has been--for decades--a highly profitable business for hospitals and imaging equipment manufacturers. But new circumstances are having an impact on the industry: Profits are no longer pouring in, and decision-makers are adjusting their strategies in response. Hospitals are discovering that they must closely monitor their radiology departments' financial performance to compete effectively in this tougher environment. At the same time, they're developing new business arrangements to help claim and protect their share of the medical imaging market. Meanwhile, clinical researchers are expanding the boundaries of imaging technology, leading to competition among modalities for market share. Changed technology and new financial considerations are combining to make hospitals' medical imaging investment decisions increasingly complex. PMID- 2227876 TI - Financial measures key to surviving pricing squeeze. PMID- 2227877 TI - Imaging devices' shifting uses affect market. PMID- 2227878 TI - Hospitals and MDs vie for imaging business. PMID- 2227879 TI - Hospitals voice objections to HCFA's proposed lab regulations. AB - HCFA is poring over 50,000 letters commenting on the proposed new clinical lab regulations. Health care providers say the regulations are unreasonably complex. As a result, "It's very likely the standards will be changed," says Thomas Morford, HCFA's health standards director. PMID- 2227880 TI - Patient-centered care: can your hospital afford not to have it? AB - A new survey tool to measure the personalization of patient care is helping hospitals look beyond the quantifiable and the clinical and zero in on the patient's perception of care. "Assuming good technology and good doctors, more patients are basing their choice [of a hospital] on ... differences in personal service," says one of the survey's managers. PMID- 2227881 TI - The delivery challenges posed by Canada: a bilateral view. AB - The Canadian health care system continues to appeal to Americans looking for alternatives to our own system. But, according to administrators who have worked in both, there are pluses and minuses to consider in each system. PMID- 2227882 TI - AHA data: net patient margins fall below one percent. PMID- 2227883 TI - Why hospitals lose services to their physicians. AB - Financial considerations are driving physicians to set up shop for themselves, say hospital CEOs. In fact, two-thirds of respondents say that their hospitals have lost services to competition from physicians. Other CEOs contend that physicians end up competing with their hospital because neither side is able to find common ground for joint ventures. PMID- 2227885 TI - Can CEOs survive medical staff opposition? AB - The odds are stacked against CEOs who hope their jobs will survive embattled relations with their medical staffs. An estimated 50 to 75 percent of CEOs who are fired lose their jobs as a direct result of medical staff conflicts. Some CEOs who have survived such conflicts say that the key is finding unusual solutions to conventional problems. PMID- 2227884 TI - PRRB ruling alters bond refunding outlook. AB - A recent ruling by the Provider Reimbursement Review Board on an accounting change for hospital bond refinancing may compel some CEOs to reconsider refinancing now. Hospitals may not be able to claim this loss once capital reimbursement is folded into the prospective pricing system, experts warn. Hospitals should accelerate their refundings--assuming, of course, that market conditions are favorable. PMID- 2227886 TI - The NLRB: its many faces can be deceiving. AB - Unions are gearing up for a hospital-organizing blitz, say three attorneys. Consequently, hospitals will have to learn to deal with the National Labor Relations Board and its "multiple personalities." The NLRB acts as investigator, grand jury, prosecutor, judge, and executioner, the attorneys warn. In the world of the NLRB, you stand charged without knowing the charges. PMID- 2227887 TI - Second quarter Monitrend II data from AHA. PMID- 2227888 TI - CEOs as risk takers--from vision to reality. AB - Health care management today is inherently risky. And because of the environment of high CEO turnover and bottom-line responsibility in which executives work, some CEOs become enmeshed in a crisis-management mode on a day-to-day basis. But there are some administrators with broader visions of what their institutions should be and what they should achieve, and who are willing to risk their reputations--and more--to bring those visions to reality. From a Massachusetts' hospital system's downsizing to a California medical center's pioneering advances in technology to a Nebraska hospital system's new marketing approach to an Ohio CEO's creativity mandate, here's how six CEOs in very different situations took risks. PMID- 2227889 TI - CEO closes a hospital, yet retains support of physicians and patients. PMID- 2227890 TI - 'Yes we can' creativity spurs system to new successes. PMID- 2227891 TI - Proton beam accelerator: investing in unconventional medicine. PMID- 2227892 TI - CEO gives local corporations a new guide to measure quality. PMID- 2227893 TI - Clarkson rewrites the book on hospital marketing. PMID- 2227894 TI - Medical society campaigns to reduce red tape for physicians. AB - The American Society of Internal Medicine is launching a campaign to attack the "hassle factor" in medicine, which, physicians say, damages patient care and undermines their decisionmaking process. In a white paper titled The Hassle Factor: America's Health Care System Strangling in Red Tape, the society outlines how government and private payer regulations are increasing costs, reducing access, and hurting patient care. The degree to which these regulations are driving physicians out of practice directly affects hospitals. PMID- 2227895 TI - Avoiding unions: supervisors are the first line of defense. AB - Hospital employees voting in union elections are swayed by their feelings about their individual supervisors, labor experts say. If supervisors are to be effective in helping to avert unionization of hospital employees, they must be trained, says Diane Iorfida, senior vice-president of human resources at University Hospitals of Cleveland (OH) and president of the Chicago-based American Society for Health Care Human Resources Administration of the American Hospital Association. Supervisor training, according to Iorfida, should be an ongoing process and not a one-time response to the immediate possibility of unionization. PMID- 2227896 TI - Hospital exec helps shape ProPAC policy. PMID- 2227897 TI - Patient relations director promotes customer loyalty. PMID- 2227898 TI - Sports medicine attracts a young, healthy market. PMID- 2227899 TI - Targeting teens as future employees. PMID- 2227900 TI - Survey: executives expect increases in purchasing budgets. PMID- 2227901 TI - Nursing homes seek advance directives. PMID- 2227902 TI - Medical staff changes reflect external pressure. PMID- 2227903 TI - Teambuilding: it starts at the top--of a tree? AB - Management experts say that teamwork begins at the top--with senior executives. For senior executives at the Saddleback Memorial Medical Center, Laguna Hills, CA, teamwork improvement started last March at the top of a tall pine tree. The Saddleback team's deeds of daring were part of a sophisticated four-and-a-half day training session at a special camp in the California mountains. The program challenged the hospital group to move beyond its current levels of teamwork. PMID- 2227904 TI - Corporate culture must foster innovation. PMID- 2227905 TI - Flexible schedules are vital to CEO success. PMID- 2227906 TI - Recruiting must adapt to MD payment changes. AB - In summary, the adverse effects of reimbursement reform on physician recruiting can be overcome by proper planning--starting now. Hospital administrators who respond appropriately to this challenge can preserve income levels for both physicians and hospitals in the years ahead. PMID- 2227907 TI - Variation and classification of human age patterns of mortality: analysis using competing hazards models. AB - The structure of variation in human mortality patterns is explored using a five parameter competing hazards model and standard multivariate taxonomic procedures. The data consist of 281 national life tables representing a wide range of environmental and cultural regions of the world. A general or average age pattern of mortality was generated for the entire sample using multiple regression procedures. A K mean cluster analysis conducted on the residuals of the regression analysis identified seven distinct models of mortality that differ in characteristic ways from the general pattern. Four of the seven clusters have age patterns of mortality similar to the north, east, south, and west regions of the Coale and Demeny model life tables. The remaining three clusters represent regions of the world and age patterns of mortality that are not represented in the Coale and Demeny model life tables. PMID- 2227909 TI - Patterned selection of mates in St. Ouen, Jersey, and the Scilly Isles examined by isonymy. AB - Within-lineage repeated-pair isonymy is calculated as RPW = sigma [Sij(Sij - 1)]/sigma [Si(Si - 1)], in which Sij is the number of a combination of two surnames in marriages (for total RPW, in both orders, brides first and also grooms first) and Si is the corresponding number of individuals of each surname (for total RPW of both sexes). In St. Ouen the 3479 native Jersey marriages between 1634 and 1914 yield a mean total RPW of 0.03314, which can be compared with a random isonymy (Ir) of 0.02205 and a marital isonymy (Im) of 0.04942. In the most recent time periods (1830-1914) there was an increase in RPW, but the increase is small if all marriages are considered rather than only native Jersey ones. In the Scilly Isles 2827 marriages between 1725 and 1975 yield a mean total RPW of 0.05127, which compares with a mean Ir of 0.01960 and an Im of 0.05238. In each kind of isonymy there is a decline over 1850-1975 caused by increased migration to the Scilly Isles. In the Scilly Isles RPW consistently approximately equals Im, so the nonrandom component of inbreeding is fully accounted for by factors that affect marital choice in the whole lineage. In St. Ouen, however, RPW is intermediate in value between Ir and Im, so the nonrandom component of inbreeding is only partly a lineage phenomenon and is also affected by other (individual) factors in choice of spouses. PMID- 2227908 TI - Reconstructing history: the Amazonian Mura Indians. AB - We studied demographic characteristics of two Mura Indian villages. Two-hundred six inhabitants of these villages and another population were tested in relation to 30 blood and 4 saliva genetic systems. These groups exhibit high mobility and exogamy rates and high fertility but relatively low mortality and variance in number of children per woman. Hb J Oxford and albumin Maku were observed, and they show high prevalences of GPT*1 and RH*R1 but low of HP*1 compared to other South American Indians. Four electrophoretic saliva systems are reported here for the first time in a predominantly Amerindian group. The amount of polymorphism was more limited than that found in Caucasian, black, and Oriental populations. The Mura are still predominantly Indian (82%) but have African (11%) and Caucasoid (7%) admixture. Using these values, the putative ancestral Mura gene frequencies were assessed. Problems related to quantitative estimations of admixture and the factors that influence the process are discussed. PMID- 2227910 TI - Relationships estimated by isonymy among the Italo-Greco villages of southern Italy. AB - Surnames of parents and grandparents were collected from 1993 children in the primary schools of the thirteen Italo-Greco communes that lie in two areas, four communes in Reggio Calabria in the "toe" of Italy and nine in Lecce in the "heel." The coefficients of relationship by isonymy show almost no relationship between the two areas. The smaller area in Reggio Calabria Province has consistently larger coefficients of relationship between communes than the larger area in Lecce Province. The difference can be ascribed to greater accumulated random isonymy in the smaller area. These populations are not genetic isolates, but each area shows a degree of cohesiveness with respect to surnames that suggests that they are genetically somewhat distinct. Contiguous pairs of communes tend to have higher coefficients of relationship than pairs of communes separated by intervening communes. PMID- 2227911 TI - Hand locomotor functions, body structure, and epidermal ridge patterns: preliminary study. AB - The purpose of this study was to determine whether any relationships exist between hand locomotor functions and dermatoglyphic characteristics and body structure. The pilot sample consisted of 71 adult normal individuals (30 males and 41 females). The locomotor function tests included a power grip and two precision grips; dermatoglyphic features were represented by finger and palmar pattern intensities and ridge counts, and body structure by 35 head, face, trunk, and limb anthropometric measurements. Univariate and multivariate correlation analyses reveal that on average half of the variance in the locomotor hand function tests can be accounted for by a set of body and/or dermatoglyphic variables in males; this contribution is appreciably lower in females. Body longitudinal measurements and some facial measures, such as jaw length, were found to be the main correlates of either a power grip or a simple thumb-index squeeze, especially in males; head and face measurements and the size and intensity of patterns on fingers 1 and 2 were the main correlates of more complex precision tests involving complicated manipulation of objects using the thumb and index finger. These preliminary results identify some previously unknown sources of variation in dermatoglyphic patterns and contribute to a better understanding of the evolutionary aspects of the relationships between specific functional and morphologic traits in humans. PMID- 2227912 TI - Age effects and secular trend in a cross-sectional sample: application to four head dimensions in Belgian adults. AB - If longitudinal studies represent the more direct way to analyze modifications resulting from aging, often for obvious reasons cross-sectional samples can also be used for this purpose. But in this case differences between age groups cannot be identified with the effects of age only; they can also be attributed to the effects of a secular trend. It is the aim of this study to show, using four cephalic dimensions and a cross-sectional sample, the need to take into account the effect of a secular trend when the age effect is studied. In 1985 a study of head and facial measurements of 182 Belgian men, aged 25-54 years, was carried out. A simple comparison between different age groups (F tests) revealed significant differences for head breadth and facial breadths. However, no difference for head length was observed. The amplitude of the secular trend in the Belgian population is already known; thus an easy calculation is proposed to define the effects of the age factor. For head breadth the whole difference seems to be the result of the important decrease of secular trend, whereas the global increase observed for the bizygomatic and bigonial breadths results in part from the decrease resulting from the secular trend and in part from the increase resulting from the age effect. PMID- 2227914 TI - Effects of maternal birth season on birth seasonality in the Canadian population during the seventeenth and eighteenth centuries. AB - Birth records of the French-Canadian population for the period 1621-1765 were analyzed retrospectively to examine the effect of maternal birth season on the seasonal distribution of births. Preliminary examination indicated that there was a bimodal pattern in birth seasonality: a major peak in early spring, a trough in early summer, a minor peak in autumn, and a trough around December. Because this seasonality was strongly biased at the level of the first birth by the month of marriage, which was concentrated in November, the seasonality of nonfirst births (n = 32,926) was examined in relation to the four seasons of maternal birth. Mothers born in May-July showed a flatter monthly distribution of nonfirst births at a maternal age of 28 years or more. Analysis of marriage-first birth intervals indicated that mothers who married in August-October showed a lower percentage of immediate conception (intervals of 8-10 months), whereas those mothers born in May-July had a higher percentage of immediate conception. This difference in birth seasonality shown by mothers born in May-July is similar to results from early twentieth-century Japan. Some seasonal infertility factors could have affected the embryos at the earliest stage of pregnancy, modifying a part of the seasonal variation in birth rate. PMID- 2227913 TI - High fertility of Old Colony Mennonites in Mexico. AB - Old Colony Mennonites in Mexico appear to demonstrate natural fertility, using no form of artificial birth control and apparently not attempting to limit family size. The resulting fertility is nearly as high as that of the Hutterites, although the Mennonites lack the communal economic system of the latter. Most Mennonites in Mexico migrated from Canada in the 1920s, and the largest single settlement, called the Manitoba Colony, is one of four in the state of Chihuahua. A 1967 partial census obtained data from 38% of the Mennonite households. Family size in the sample was close to that in a local survey taken in the same year. Available church records matched with census forms permitted verification of and corrections to 560 female reproductive histories. The median number of live births to women over age 45 years was 9.5, compared with 10.4 in the Hutterites. Age-specific marital fertility rates and birth intervals closely resembled those of the Hutterites. PMID- 2227915 TI - Birth weight in an African-American population living under moderate ecologic stress. AB - The African-American population of McNary, Arizona, resides at an altitude of 2200 m. The lengthy winters are typically quite cold; the monthly mean temperature from November to April is 1.8 degrees C. Data from 318 singleton full term births of African-American babies from 1949 to 1972 show a mean weight of 3095 g (s.d. = 427 g). At birth 1.9% of the babies weighed at least 4 kg; 9.7% weighed less than 2.5 kg. These data suggest that altitude may have influenced birth weight in this sample. Significant patterns in birth weight exist for sex, parity, mother's age, and severity of the winter preceding the year of birth. The birth weight of female babies born following warm winters is significantly lighter than those born during years following cold winters. There are relatively fewer high-birth-weight babies, in comparison to other African-American populations. Birth weight is also significantly lighter than three other African American samples, even though African-American mothers of McNary had full-term professional care. Birth weight of African-American babies born in McNary is consistent with the overwhelming African ancestry of the African-American population of McNary. Sex differences in birth weight of babies born following cold winters can be ascribed to gender-related hereditary or physiologic factors at the level of the fetus. Maternal inactivity during particularly cold winters may be a contributing factor. PMID- 2227916 TI - Collagenous, "microscopic," lymphocytic, and other gentler and more subtle forms of colitis. PMID- 2227917 TI - Colonic lymphocytosis in patients with celiac sprue. AB - We examined colonic biopsies from 39 patients with clinical and small bowel biopsy changes of celiac sprue. In 12 of 39 patients (31%), striking lymphocytic infiltration of the superficial colonic epithelium and chronic inflammation of the lamina propria were identified. These 12 cases had a mean of 30.4 lymphocytes per 100 superficial colonic epithelial cells, compared with means of 8.4 in sprue cases without colonic epithelial lymphocytosis, 4.8 in normal controls, and 32.4 in nine cases of lymphocytic colitis without concurrent celiac sprue. No case showed subepithelial collagen layer thickening. Four patients with celiac sprue and colonic lymphocytosis also had gastric biopsies; two showed gastric lymphocytosis. Intraepithelial lymphocytes at all sites were positive for the T cell marker MT-1. These findings indicate that sprue-associated colonic lymphocytosis and lymphocytic colitis are histologically, quantitatively, and immunohistochemically indistinguishable, that the epithelial T-cell infiltration of celiac sprue occurs in glandular mucosa at all levels of the gastrointestinal tract, and that colonic subepithelial collagen deposition in patients with celiac sprue is an infrequent occurrence. These findings also suggest that gastrointestinal epithelial T-cell infiltration may be an immunologic response that is common in individuals sensitized to absorbed lumenal antigens, and that colonic lymphocytosis may occur as a response to a number of antigens, including gluten. PMID- 2227918 TI - Nuclear DNA measurements of metastatic melanoma by a computerized digital imaging system. AB - To determine the extent of nuclear DNA abnormalities and their relationship with prognosis of stage II malignant melanoma, metastatic melanomas in lymphadenectomy specimens of 22 patients were studied by a computerized digital imaging system. The DNA ploidy pattern was aneuploid in 86% of the cases and tetraploid in the remaining 14%. In metastatic melanomas, there was a single clone in one third of patients and multiple clones in the remaining two thirds. Poor survival rate was associated with multiple clones and greater than 30% of mean coefficient of variation of DNA content. With tumor progression stem-cell lines often became heterogeneous with the development of multiple clones and widespread DNA values. These abnormalities, determined by nuclear DNA ploidy analysis, provide useful prognostic information. PMID- 2227919 TI - Peripheral T-cell lymphomas: a clinicopathologic study of 75 cases. AB - Seventy-five peripheral T-cell lymphomas (PTLs) were classified according to the recently proposed "Updated Kiel Classification of Non-Hodgkin's Lymphomas" (mycosis fungoides and Sezary's syndrome excluded). Thirty-seven PTLs belonged to the low-grade category (T-cell chronic lymphocytic leukemia [T-CLL], 3; lymphoepithelioid, 4; angioimmunoblastic, 22; T-zone, 6; pleomorphic small cell, 2) and 38 belonged to the high-grade category (pleomorphic medium and large cell, 24; immunoblastic, 1; large-cell anaplastic Ki-1-positive, 13). Loss of pan-T antigens occurred exclusively in high-grade PTLs; on paraffin sections UCHL 1 was slightly more sensitive than MT 1. Sixty patients presented with lymphadenopathy and 15 patients (20%) presented with extranodal disease most frequently affecting the skin and upper aerodigestive tract. B-cell lymphoma symptoms were found in 43 cases (57%) and bone marrow involvement (T-CLL excluded) was found in 12 cases (17%). Staging (T-CLL excluded) revealed stage I in 13%, stage II in 15%, and stages III and IV in 72% of the cases. Among the intensively treated patients, 37% achieved complete remission and 15 are still in complete remission after 4 to 79 months (median: 24 months). The overall median survival (MS) rate was 23 months. Peripheral T-cell lymphoma of pleomorphic medium and large-cell type was the most aggressive lymphoma (MS: 8 months). B-cell lymphoma symptoms, bone marrow involvement, and Ki-67 positivity 60% or greater significantly shortened survival times, whereas age (under 60 versus over 60 years), stage (I and II versus III and IV), and grade had no significant influence. Ki-67 reactivity was found to be a prognostic factor which allows prediction of probable poor outcome, especially in cases with limited stage of disease. PMID- 2227920 TI - Immunohistologic analysis of small lymphocytic infiltrates of the orbit and conjunctiva. AB - In a prior study we reported that monotypic immunoglobulin expression significantly correlated with an increased risk of dissemination by small lymphocytic infiltrates (SLIs) of the orbit and conjunctiva. However, less than half of all monotypic SLIs disseminated. In this study, we applied a large panel of monoclonal antibodies to cryostat sections of orbital and conjunctival SLIs to address two questions. First, might immunohistologic results other than immunoglobulin staining predict which patients with monotypic SLIs will develop disseminated lymphoma? Second, what is the usefulness of these findings in the diagnosis of orbital and conjunctival SLIs? We found that immunohistologic results did not significantly predict or correlate with disseminated lymphoma in patients with monotypic SLIs, either at time of presentation (ie, staging evaluation positive) and/or subsequently. However, three monotypic infiltrates (10%) had a proliferative rate (Ki-67-positive) of 20% or greater, and all three cases disseminated. Regarding the usefulness of the antibody panel, a B to T cell ratio of 4 or greater (76%), anomalous pan-T cell antigen expression by B cells (38%), and pan-B cell antigen loss (15%) were found exclusively in monotypic SLIs. Combining these results, 80% of monotypic SLIs had additional immunophenotypic criteria of lymphoma. Thus, these findings appear to be useful, although less helpful than immunoglobulin staining, and provide another means of immunophenotypic diagnosis when the results of immunoglobulin staining are technically unsatisfactory or difficult to interpret. We were unable to detect anomalous antigen expression or antigen loss in polytypic infiltrates, including one lesion which locally recurred 30 months later as a histologically indistinguishable, clearly monotypic SLI. We attribute the absence of these findings in polytypic SLIs to their relatively infrequent occurrence in monotypic infiltrates and/or to our inability to detect small clones of malignant cells (if present) by our immunohistologic methods. PMID- 2227921 TI - Genotype and phenotype: a practical approach to the immunogenetic analysis of lymphoproliferative disorders. AB - Determination of cell lineage and clonality in lymphoproliferative disorders (LPD) is greatly enhanced by molecular genetic analysis in conjunction with morphologic and immunologic techniques. We now report on a technique in which we used cryostat-cut, fresh-frozen sections (CCFFS) prepared from tissues in a manner that allows DNA hybridization studies to be coordinated readily with routine morphologic and immunohistologic studies. Thirty-seven cases representing a broad spectrum of reactive and malignant LPD were examined with this method. Samples of DNA were extracted from frozen sections, subjected to Southern blot hybridization, and probed for rearrangements of the immunoglobulin (Ig) heavy chain and the kappa and lambda light-chain genes, as well as for the T-cell receptor beta-chain gene. We also evaluated the effects of (1) diagnostic category of LPD, (2) volume of the tissue sample, and (3) fibrosis, necrosis, and ice crystal artifacts in the sample on the recovery of DNA. Ice artifact and sample size had the greatest negative impacts on the quantity and condition of DNA recovered. Of 19 samples involved by B-cell LPD, the results of immunogenetic studies were consistent with the immunophenotypes in all but one case. Of the T cell lymphomas from which sufficient DNA was available (three out of five of the T-cell cases), all showed rearrangements of the T-cell beta-chain gene. In order to reduce sample processing time, we evaluated alternate blot hybridization methods, rapid alkaline transfers, and direct hybridization of synthetic oligonucleotides in dried agarose gels, and found that they decreased the time required for hybridization studies. In summary, the use of CCFFS as the source of DNA allows study of gene rearrangements and, at the same time, preserves frozen tissue blocks in tumor banks for further immunologic studies. The development of time-effective methods will make the routine use of molecular-genetic analysis more practical in the diagnostic hematopathology laboratory. PMID- 2227922 TI - Metaplastic carcinomas of the breast: V. Metaplastic carcinoma with osteoclastic giant cells. AB - The clinical and pathologic features of 29 examples of mammary metaplastic carcinoma with osteoclastic giant cells (OGC) in the stroma are reported. A bland spindle cell or sarcomatous component dominated these neoplasms, although infiltrating duct carcinoma was present in 23 cases, and intraductal carcinoma was present in six cases. In all 29 neoplasms, the carcinoma was admixed or contiguous with the stroma. Osteoclastic giant cells were admixed within the cellular stroma, and were intimately associated with prominent thin-walled vessels. Hemorrhage and hemosiderin deposition were common. Osteoclastic giant cells were immunoreactive for vimentin and, to a lesser extent, actin, and uniformly not immunoreactive for keratins, confirming their mesenchymal nature. The stromal component of 63% of neoplasms tested was immunoreactive for keratin, 33% was immunoreactive for epithelial membrane antigen, 54% reacted for S-100 protein, 84% reacted for actin, and 100% was immunoreactive for vimentin. Nineteen neoplasms had osteoid, bone, or cartilage, but these were a prominent component in only five neoplasms and OGC were not limited to these areas. The disease-specific cumulative 5-year survival rate for patients with metaplastic carcinoma with OGC was 68%, similar to rates for patients with matrix-producing carcinoma (68%), spindle cell carcinoma (64%), and squamous carcinoma of ductal origin (63%), but notably different from that of patients with carcinosarcoma (49%). Of 17 women with axillary node dissection, only two had metastases. Eleven women developed distant metastases, most commonly to the lungs. Metastasis present at or following initial surgery was an ominous sign, as all 11 women with metastases died from tumor. Size and microscopic circumscription were significant factors in predicting disease progression. PMID- 2227924 TI - Sequestrated meningoceles of scalp: extracranial meningeal heterotopia. AB - Sequestrated meningocele of the scalp has seldom been reported and is difficult to diagnose. Clinically it resembles dermoid cyst, hemangioma, or alopecia; radiographs and computed tomographic scans reveal no cranial bone defect, and surgery discloses no communication with the cranial cavity. Histologically, the lesion is characterized by a loose arrangement of connective tissue in dermis and subcutis, associated with flattened cells around collagen fibers (meningothelial cells). Most examples are very vascular, sometimes mimicking angioma, and about one third contain small necrotic foci. The meningothelial nature of the lesion is shown by its architectural similarity to communicating meningocele, and its identical immunoperoxidase reactions with vimentin and epithelial membrane antigen. In the 12 cases reported herein, most lesions were small (1 to 1.5 cm), and all but one were noted at birth but usually not resected until the patient had reached age 1 to 4, and one not until the patient was 31 years of age. Five lesions were not midline. We have been unable on histologic grounds to determine whether meningoceles are communicating or sequestrated. Compared with 20 communicating meningoceles, the sequestrated lesions were usually smaller, found in slightly older patients, and much less likely to be associated with hydrocephalus. The local excision of scalp lesions in children should include a search for a small intracranial connection. PMID- 2227923 TI - Mixed medullary-papillary carcinoma of the thyroid: a previously unrecognized variant of thyroid carcinoma. AB - Two unusual medullary carcinomas of the thyroid gland and their metastases contained a population of cells (20% to 25%) with the characteristic clear nuclei of papillary carcinoma. The predominant component of the tumors exhibited the typical growth pattern and cytologic features of medullary carcinoma with abundant amyloid deposits. The cells with clear nuclei lined follicle-like or tubular structures. In both the primary and the metastatic lesions, immunoreactive thyroglobulin was demonstrated only in the cells with clear nuclei, while calcitonin, carcinoembryonic antigen, and neuron-specific enolase were present only in cells of the predominant medullary carcinomatous component. Moreover, intense and diffuse staining for cytokeratin was seen only in the cells with clear nuclei, but not in those of the major medullary carcinomatous component. These findings suggest the existence of a distinctive variant of mixed medullary-papillary carcinoma that can be recognized with routine stains. PMID- 2227925 TI - Corneal and conjunctival crystals in paraproteinemia. AB - A 64-year-old woman with bilateral corneal and conjunctival crystal deposition was evaluated. A biopsy of her conjunctiva showed intracytoplasmic inclusions of immunoglobulin crystals in fibrocytes, macrophages, and endothelial cells. Serum protein electrophoresis showed elevated kappa and IgA light and heavy chains which corresponded with immunoperoxidase staining results of the conjunctival biopsy. Conjunctival and corneal crystal deposition may be indicative of paraproteinemia, and histopathologic examination of a conjunctival biopsy may be useful in diagnosing this condition. PMID- 2227926 TI - Giant cell tumor of the pancreas of mixed osteoclastic and pleomorphic cell type: evidence for a histogenetic relationship and mesenchymal differentiation. AB - We describe a giant cell tumor of the pancreas composed of a mixture of osteoclastic and pleomorphic cell types. This rare tumor had a unique immunohistochemical profile. Both types of tumor giant cells stained for vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, synaptophysin, muscle actin, and neuron-specific enolase, but not for epithelial markers. Electron microscopy showed cells which resembled primitive fibroblasts and osteoclast with no epithelial features. These findings are most consistent with mesenchymal differentiation. The extensive homologies in immunohistochemical staining of both osteoclastic and pleomorphic giant cells in this case indicates that these cells are histogenetically related. PMID- 2227927 TI - Composite carcinoid-adenocarcinoma of ampulla of Vater. PMID- 2227928 TI - Use of energy-dispersive X-ray analysis for detection of Teflon in tissue sections. PMID- 2227930 TI - Variability in expression of common fragile sites: in search of a new criterion. AB - Fragile sites are nonrandom, heritable sites on chromosomes that can be induced to form gaps, breaks, and rearrangements under specific conditions. There is currently no established criterion to define a common fragile site. We applied seven published criteria to our data from three groups of subjects: (1) three pairs of like-sexed twins, (2) four unaffected von Hippel-Lindau (VHL) family members, and (3) six patients affected with VHL disease. Substantial differences were present in the numbers of sites considered positive by these criteria. While some of this variability can be attributed to technical factors, our data illustrate the problems in comparing results from different studies to assess the significance of fragile sites. A recently published criterion is based upon the Poisson distribution. We found this criterion to be flawed in its presentation, and furthermore, the Poisson distribution did not provide an adequate approximation to our data. We propose here an alternative approach based upon the negative binomial distribution. PMID- 2227931 TI - Y isochromosome associated with a mosaic karyotype and inactivation of the centromere. AB - A patient with azoospermia and a Y isochromosome is described. The breakpoint producing this i(Y) was within the terminal short arm of the Y chromosome. Lymphocyte cultures from peripheral blood contained a high proportion of 45,X cells and cells with different Y-chromosome rearrangements. The i(Y) had either a monocentric or dicentric appearance. In dicentrics, anti-kinetochore immunofluorescence was present at both centromeres. However, this was also true for most of the functional monocentrics (pseudodicentrics). Kinetochore staining was generally positive at the site of the inactive centromeres; only a minority of the suppressed centromeres had lost their antigenic properties. Permanently growing lymphoblasts consistently showed a monocentric i(Y) with only one fluorescing kinetochore; the immunonegative Y centromere did not recover antigenicity. PMID- 2227929 TI - The critical region on the human Xq. AB - Adult female carriers of balanced X; autosome translocations (118 cases) and of balanced X inversions (31 cases) have been collected from the literature. Forty five of the 118 translocation carriers in whom the break was in the critical region (Xq13-q22, Xq22-q26, separated by a narrow region within Xq22) showed gonadal dysgenesis. Seven of the 31 inversion carriers in whom the break was in the same region also had gonadal dysgenesis, whereas the remaining 24 were normal in this respect. The critical region consists mainly of Q-bright material, and is the fifth brightest segment in the human genome. The region contains relatively few genes. It is possible that meiotic crossing-over, rarely, if ever, takes place in it. The critical region may therefore consist of two "supergenes" whose integrity must be maintained to allow normal ovarian development. The effect exerted by this region differs from other known position effects, in that it is independent of the breakpoint within the region and of the chromosome bands to which the broken ends are attached. One possible mechanism causing this effect might be a change in the replication order of the chromosome bands, which, in turn, might affect their function. PMID- 2227933 TI - Significance of structural chromosome aberrations in human sperm: analysis of induced aberrations. AB - A significant increase in the incidence of structural chromosome anomalies has been observed in the sperm of patients treated with radio and/or chemotherapy for different types of cancer when analyzed by the interspecific fertilization of hamster eggs. The analysis of these aberrations shows that while in controls only 9.4% of structural abnormalities are of the stable type, in treated patients this figure increases to 39.3%, thus indicating that the anomalies have not been produced during the fertilization of the hamster egg. However, it is possible that part, or even most, of the breaks appear as a result of a reduced repair capacity of sperm chromosomes in the cytoplasm of the hamster egg. PMID- 2227932 TI - Deletion of specific sequences or modification of centromeric chromatin are responsible for Y chromosome centromere inactivation. AB - Stable dicentric chromosomes behave as monocentrics because one of the centromeres is inactive. The cause of centromere inactivation is unknown; changes in centromere chromatin conformation and loss of centromeric DNA elements have been proposed as possible mechanisms. We studied the phenomenon of inactivation in two Y centromeres, having as a control genetically identical active Y centromeres. The two cases have the following karyotypes: 45, X/46,X,i(Y)(q12) and 46,XY/47,XY,+t(X;Y) (p22.3;p11.3). The analysis of the behavior of the active and inactive Y chromosome centromeres after Da-Dapi staining, CREST immunofluorescence, and in situ hybridization with centromeric probes leads us to conclude that, in the case of the isochromosome, a true deletion of centromeric chromatin is responsible for its stability, whereas in the second case, stability for its stability, whereas in the second case, stability of the dicentric (X;Y) is the result of centromere chromatin modification. PMID- 2227934 TI - Identification of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APART*Q0) leading to 2,8-dihydroxyadenine urolithiasis. AB - Homozygous deficiency of a purine salvage enzyme, adenine phosphoribosyltransferase (APRT), causes urolithiasis and renal failure. There are two known types of homozygous APRT deficiencies; type I patients completely lack APRT activity while type II patients only partially lack such activity. All type II patients possess at least one APRT*J allele with a substitution from ATG (Met) to ACG (Thr) at codon 136. Type I patients are considered to possess two alleles (APRT*Q0) both of which code for complete deficiencies. Thus, some patients with type II APRT deficiencies may have a genotype of APRT*J/APRT*Q0. As no individuals with such a genotype have previously been identified, we performed extensive analysis on four members of a family by (1) the T-cell method for the identification of a homozygote, (2) the B-cell method for the identification of heterozygotes, and (3) oligonucleotide hybridization after in vitro amplification of a part of genomic APRT sequence for the identification of APRT*J and non APRT*J alleles. We report here the first evidence that 2,8-dihydroxyadenine urolithiasis developed in a boy aged 2 years with a genotype of APRT*J/APRT*Q0. PMID- 2227935 TI - Locus assignment of human alpha-globin structural mutants by selective enzymatic amplification of alpha 1 and alpha 2-globin cDNAs. AB - We have used the powerful methodology of DNA enzymatic amplification in order to assign human alpha-globin structural mutants to one of the two highly homologous alpha-globin genes. Selectively amplified alpha 1 and alpha 2-globin cDNAs were dot-blotted and further hybridized to synthetic oligonucleotides encompassing either the normal or the mutated sequences. The generated signals corresponded specifically to one of the two alpha-globin genes. Using this approach the alpha globin structural mutants J-Buda and G-Pest were found to be encoded by the alpha 2 and the alpha 1-globin genes, respectively. Furthermore, the exact nucleotide changes were determined. We propose this technique to serve as a simple and definitive method for assigning alpha-globin structural mutants. PMID- 2227936 TI - Involvement of the region 13q14 in a patient with adamantinoma of the long bones. AB - A cytogenetic analysis of a lung metastasis of an adamantinoma of the tibia, a rare tumor of the long bones, revealed a karyotype 52, XY, t(7;13)(q32;q14), +7, +12, +13, +19, +der(7) t(7;13), +der(13) t(7;13). The t(7;13) was found to be constitutional in the patient and was also present in peripheral blood lymphocytes of his unaffected father. However, both subjects displayed normal levels of esterase D enzyme activity. PMID- 2227937 TI - Investigation of three patients with the "ring syndrome", including familial transmission of ring 5, and estimation of reproductive risks. AB - We report three cases of ring chromosome 5 [r(5)], two familial (mother and daughter) and one sporadic. The phenotype resembled that of the "ring syndrome" with prenatal onset of short stature, growth retardation, mild facial dysmorphism and normal psychomotor development. Extended metaphase and prometaphase chromosome preparations using G-, R- and Q-banding and scanning electron microscopy (SEM) failed to demonstrate deletion in the ring 5. Flow karyotype using the FACS cell sorter and peak area analysis showed the r(5) to be in the same position as the normal chromosome 5. The deletion that is presumably associated with ring formation appears to involve less that one megabase of DNA. In the "complex" rings, high resolution SEM showed fragile sites at the 5q34 and 5q35 region with frequent deletions at that site. A literature survey suggests that when a parent carries a ring chromosome about 80% of recognised pregnancies result in live birth. Of these, about half have a normal phenotype and karyotype, and half inherit the parental ring; about half of those acquiring the ring (20%) show significant mental retardation. PMID- 2227938 TI - The human QARS locus: assignment of the human gene for glutaminyl-tRNA synthetase to chromosome 1q32-42. AB - We have used a cDNA encoding the core region of the human glutaminyl-tRNA synthetase to determine the chromosomal localization of the corresponding gene. Southern blots of restricted DNA from a panel of rodent-human cell lines and in situ chromosome hybridization gave identical results showing that the human gene locus for glutaminyl-tRNA synthetase resides on the distal long arm of chromosome 1. There are now nine mapped aminoacyl-tRNA synthetase genes in the human genome. PMID- 2227939 TI - Molecular analysis of the human MHC class I region in hereditary haemochromatosis. A study by pulsed-field gel electrophoresis. AB - The unknown allele that predisposes to the development of haemochromatosis in man has been localized to the HLA class I region on the short arm of chromosome 6. We have utilized pulsed-field gel electrophoresis in conjunction with probes that map within, or in the vicinity of, this region to search for structural lesions that may further define the disease locus. Using the enzyme Mlu I, fragments that associated specifically with the HLA-A23, A31 and B8 alleles were identified. However, in members of three pedigrees affected by haemochromatosis, and in six unrelated patients with the disorder, no disease-specific differences were detected in the DNA fragments with four restriction enzymes and eight probes when compared with healthy individuals. These data suggest that the lesion responsible for hereditary haemochromatosis lies beyond the resolution of this technique and does not involve large structural deletions or extensive re-arrangements in this highly polymorphic region of the genome. PMID- 2227940 TI - Molecular characterisation of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null(Newport) (Gly115----Ser) and (Pi) Z Wrexham (Ser 19----Leu). AB - Two single point mutations in the alpha-1-antitrypsin gene, resulting in AAT deficiency, have been characterised in heterozygotes by DNA amplification and direct sequencing. The mutations result in amino acid substitutions, Gly115--- Ser and Ser-19----Leu, in the leader sequence, respectively, and have been designated Pi Null(Newport) and Pi Z Wrexham. In the two families studied the mutations occur on chromosomes which also carry the common mutation causing Z deficiency. Individuals with such a deficiency are, therefore, compound heterozygotes. It is not known if these particular mutations would only cause a mild form of AAT deficiency in the absence of the Z mutation as they do not appear to cause predictable folding abnormalities. They do, however, result in severe deficiency when the Z mutation occurs in the same gene. PMID- 2227941 TI - In situ chromosome preparation technique for simultaneous cytogenetic and immunocytochemical studies on cell cultures of solid tumors. AB - Immunophenotyping of cultured cancer cells requires intact antigenic structures; these are mostly destroyed by conventional chromosome preparation techniques. Thus, the simultaneous cytogenetic and immunocytochemical characterization of solid tumor cells appears unfeasible. Here, we describe a novel method that allows in situ chromosome preparation from monolayer cultures of solid tumor cells without affecting their immunological features. Using this technique, it is possible to achieve detailed cytogenetic data including chromosome banding together with the demonstration of cytoplasmic and nuclear antigens within the same tumor cells. PMID- 2227942 TI - Rapid diagnosis of Miller-Dieker syndrome and isolated lissencephaly sequence by the polymerase chain reaction. AB - Probe YNZ22 (D17S5) is a highly polymorphic, variable number tandem repeat (VNTR) marker previously shown to be deleted in all patients with the Miller-Dieker syndrome (MDS) but not in patients with isolated lissencephaly sequence (ILS). Primers were constructed to the unique sequence flanking the polymorphic, repetitive region of YNZ22 for amplification by the polymerase chain reaction (PCR). Analysis of 118 normal individuals revealed 12 alleles (differing in copy number of a 70-bp repeat unit) ranging in size from 168 to 938 bp. A retrospective study of eight MDS and six ILS patients was consistent with Southern blot analysis in all cases except one. In the latter, a very large allele (12 copies of the repeat unit) in a patient and her mother failed to amplify on initial attempts, but was successfully amplified by reducing the concentration of genomic DNA used in the reaction. Prospective studies on two MDS and five ILS patients were successfully performed and confirmed in all cases by Southern blot analysis. From the total sample, restriction fragment length polymorphism (RFLP) analysis was fully informative in four of ten MDS patients and showed a deletion in all four cases. Nine of eleven ILS patients were heterozygous and therefore not deleted for YNZ22. Development of primers for additional polymorphic markers in the Miller-Dieker region will lead to a rapid PCR-based diagnostic approach for all MDS and ILS patients. PCR typing of YNZ22 will also facilitate use of this marker in other applications, including genetic linkage, paternity and forensic studies, and analysis of loss of heterozygosity in tumors. PMID- 2227943 TI - Close linkage of the Wilson's disease locus to D13S12 in the chromosomal region 13q21 and not to ESD in 13q14. AB - Wilson's disease (WD) is an autosomal recessive disorder resulting in copper accumulation notably in liver and brain tissue. Linkage of the WD locus (WND) to ESD at 13q14 was first shown by studies in families of Middle Eastern origin using the isozymic polymorphism of esterase D. Using RFLPs detected by the ESD cDNA we could not confirm this reported close linkage in an analysis of 17 WD families of northwest European origin. A tight linkage was detected, however, to the marker D13S12, located more distally at 13q21. No obligate cross-overs were detected in 63 gametes informative for this marker. Our data confirm an assignment of WND to 13q14-21. Its localization, however, seems to be more distal to ESD than previously reported. Although genetic heterogeneity cannot be excluded, the observed differences between the two populations are probably due to random variation. PMID- 2227944 TI - Deletion 3q27----3qter associated with a new skin disorder? PMID- 2227945 TI - Complex translocations, simple variant translocations and Ph-negative cases in chronic myelogenous leukaemia. AB - A proportion of cases of chronic myelogenous leukaemia (CML) has been described either (1) with a variant translocation, or (2) without the apparent involvement of both 9q34 and 22q11 (Ph-negative CML). All variant translocations have been further demonstrated to be complex implicating 9q34,22q11, plus another breakpoint on a variable chromosome. Complex translocations may be due to two successive events. Some of the breakpoints on the variable chromosome appear to be recurrent, and these remain to be studied for prognostic significance. Ph negative CML comprises (1) cases of submicroscopic (hidden) insertion of 9q34-ABL within 22q11-BCR, and (2) cases without BCR-ABL rearrangement. We propose this last category to be called "CML-like disease", not to be confused anymore with true CML, and consequently to be studied as a separate entity. PMID- 2227947 TI - Regional assignment of the human thymidylate synthase (TS) gene to chromosome band 18p11.32 by nonisotopic in situ hybridization. AB - The human thymidylate synthase (TS) gene was regionally assigned to chromosome band 18p11.32 by nonisotopic in situ hybridization using biotinylated cDNA (1.1 kb insert) and genomic DNA (6.8 kb insert) probes of the human gene. There have been two provisional assignments for the TS gene to 18pter-q12 and 18q21-qter. The present result confirmed the first of these and further localized the TS gene to the telomeric region of the short arm of chromosome 18. The TS gene appears to be a novel telomeric anchor point for the construction of both physical and genetic linkage maps of human chromosome 18. PMID- 2227946 TI - Identification and characterization of normal length nonfluorescent Y chromosomes: cytogenetic analysis, southern hybridization and non-isotopic in situ hybridization. AB - In two female patients with a 45,X/46,X, +mar karyotype the marker chromosomes were identified as normal length nonfluorescent Y chromosomes (nlYnf) using non isotopic in situ hybridization (NISH) complementary to routine cytogenetic analysis and Southern hybridization. The recognition of the nlYnf as isodicentric in both patients illustrates and confirms the usefulness and importance of NISH in the identification and characterization of this and many other types of complex chromosome rearrangements. PMID- 2227948 TI - Direct carrier detection by in situ suppression hybridization with cosmid clones of the Duchenne/Becker muscular dystrophy locus. AB - A basic problem in genetic counseling of families with Duchenne/Becker muscular dystrophy (DMD/BMD) concerns the carrier status of female relatives of an affected male. In about 60% of these patients, deletions of one or more exons of the dystrophin gene can be identified. These deletions preferentially include exon 45, which can be detected by multiplex polymerase chain reaction (PCR) and Southern blot analysis of genomic cosmid clones that map to this critical region. As a new approach for definitive carrier detection, we have performed chromosomal in situ suppression (CISS) hybridization with these cosmid clones in female relatives of four unrelated patients. In normal females, most metaphases showed signals on both X chromosomes, whereas only one X chromosome was labeled in carriers. Our results demonstrate that CISS hybridization can define the carrier status in female relatives of DMD patients exhibiting a deletion in the dystrophin gene. PMID- 2227949 TI - Localization of the gene for amiloride binding protein on chromosome 7 and RFLP analysis in cystic fibrosis families. AB - The apical sodium channel is essential for sodium reabsorption by the kidney. Its activity is blocked by the diuretic amiloride. Using a human cDNA coding for the amiloride binding protein (ABP), the corresponding structural gene was mapped to human chromosome 7q34-q36 by in situ hybridization. This region flanks the region implicated in cystic fibrosis (7q32). Because an alteration of the amiloride sensitive sodium channel function has been suggested in cystic fibrosis, a possible link between the ABP gene and this disease was analyzed by restriction fragments length polymorphism (RFLP) analyses. From this study, it appears that the gene coding for ABP is not directly modified by mutations causing cystic fibrosis. PMID- 2227950 TI - X chromosome imprinting in fragile X syndrome. AB - Laird et al. (1987) hypothesized that there are at least four cis-acting alleles or 'chromosome states' at Xq27 that increasingly delay replication at this chromosomal area resulting in its increasing fragility in vitro. When on the inactive X chromosome, the proposed third ('mutated') allele can permanently block reactivation of its cis Xq27 area as the chromosome passes through female meiosis. Males and some females who inherit such an 'imprinted' fragile X chromosome (the fourth proposed allele) will be clinically affected due to impaired transcription of genes in the 'imprinted' Xq27 area. To test this hypothesis, late replication reverse banding patterns at Xq27 were evaluated in cultured lymphoblastoid cell lines from 25 subjects. Our data suggest that DNA replication of the presumed 'imprinted' Xq27 region in affected fragile X patients is indeed later relative to Xq27 on the active X chromosome in other subjects. These results support in part Laird's hypothesis of chromosomal imprinting in fragile X syndrome. PMID- 2227951 TI - Crossovers within a short DNA sequence indicate a long evolutionary history of the APRT*J mutation. AB - Adenine phosphoribosyltransferase (APRT) deficiency causing 2,8-dihydroxyadenine urolithiasis and renal failure is present at a high frequency among the Japanese but not other ethnic groups. A special type of mutant allele, designated APRT*J, with a nucleotide substitution at codon 136 from ATG (Met) to ACG (Thr) is carried by approximately 79% of all Japanese 2,8-dihydroxyadenine urolithiasis patients. We analyzed mutant alleles of 39 APRT deficient patients using a specific oligonucleotide hybridization method after in vitro amplification of a part of the genomic APRT sequence. We found that 24 had only APRT*J alleles. Determination of the haplotypes of 194 APRT alleles from control Japanese subjects and of the 48 different APRT*J alleles indicated that normal alleles occur in four major haplotypes, whereas all APRT*J alleles occur in only two. These results suggest that all APRT*J alleles have a single origin and that this mutant sequence has been maintained for a long period, as calculated from the frequency of the recombinant alleles. PMID- 2227952 TI - Characteristic chromosome abnormalities, including rearrangements of 6p, del(7q), +12, and t(12;14), in 44 uterine leiomyomas. AB - The cytogenetic analysis of 224 leiomyomas from 138 patients is presented. An insufficient number of mitoses was found in 35 tumors, normal karyotypes in 145, and clonal chromosome aberrations were detected in 44. The three previously identified cytogenetic subgroups were all represented in this series: del(7) (q21.2q31.2) was found in 11, trisomy 12 in five, and t(12;14)(q14-15;q23-24) in one leiomyoma. Rearrangements of 6p, including deletions, inversions, and various translocations, were found in eight tumors, thus delineating a new cytogenetic subgroup of uterine leiomyoma. The remaining 21 karyotypically abnormal tumors had nonrecurrent changes. One leiomyoma had two cytogenetically unrelated clones characterized by del(7)(q21.2q31.2) and +12. Karyotypic changes in two separate leiomyomas from the same uterus were identified in five patients; in three of them, different anomalies were found in the two tumors, whereas cytogenetically identical aberrations - del(7q) and dic(21;22) - were detected in two macroscopically discrete tumors. These findings suggest that whereas some multiple leiomyomas originate independently, others may be derived from the same neoplastic clone. PMID- 2227953 TI - Distal trisomy 14q. I. Clinical and cytogenetical studies. AB - Two cases of de novo duplication of the distal part of the long arm of chromosome 14 are reported. In one case, the partial trisomy of 14q is due to translocation of a segment (14q24 to 14qter) at the end of the satellite stalk of chromosome 14. The clinical picture is very severe. In the second case, a tandem duplication in 14 (q23----q32) is present with only minor malformations and mild mental retardation. PMID- 2227954 TI - Evidence that expression of Sp alpha I/65 hereditary elliptocytosis is compounded by a genetic factor that is linked to the homologous alpha-spectrin allele. AB - Many cases of hereditary elliptocytosis (HE) result from mutated spectrin alpha chains. It has repeatedly been observed that the amount of a mutant alpha-chain is different in various affected individuals, resulting in clinical pictures of variable severity. The different levels are thought to result from different percentages of the alpha-spectrin allele in trans. Such percentages, in turn, could be under genetic control. We tested this hypothesis in a large Algerian family with Sp alpha I/65 HE. In an informative sibship, we found three persons with a distinctly high level of expression of the Sp alpha I/65 variant, suggesting the existence, in trans, of a low percentage alpha-allele. The alpha spectrin gene haplotype associated with the latter was constantly - + -, based on the XbaI, PvuII, and MspI polymorphic sites. In contrast, a basal level of expression of the Sp alpha I/65 variant in the same sibship indicated, in trans, the existence of a normal percentage alpha-allele. The haplotype corresponding to this other alpha-allele was + - +. Study of another generation of the family showed, however, that the - + - haplotype could also be linked to a normal percentage alpha-allele. These results are consistent with the view that the expression level of alpha I/65 spectrin (and of other types of alpha-variants) is compounded by a genetic factor that is linked to the normal alpha-allele in trans. The low percentage allele itself remains silent in the simple heterozygous state. PMID- 2227955 TI - Acute intermittent porphyria caused by a C----T mutation that produces a stop codon in the porphobilinogen deaminase gene. AB - A mutation of the porphobilinogen (PBG) deaminase gene that produces the cross reacting immunological material (CRIM)-negative type of acute intermittent porphyria (AIP) has been identified in one of 43 unrelated patients with this form of the disorder. The mutation is a C----T transition that abolishes a PstI recognition site in exon 9 of the gene and converts a codon for glutamine to a stop codon. PMID- 2227956 TI - Clinical and genetic heterogeneity in retinitis pigmentosa. AB - The clinical course of defective vision and blindness has been investigated in relation to different modes of genetic transmission in a large series of 93 families with retinitis pigmentosa (RP). For autosomal dominant RP, two clinical subtypes could be distinguished according to the delay in macular involvement. In the severe form, macular involvement occurred within 10 years, while in the mild form, macular involvement occurred after 20 years. Interestingly, a significant increase of mean paternal age (38.8 years, mean controls in France = 29.1 years, P less than 0.001) was found in this form of RP, a feature which is suggestive of new mutations. For autosomal recessive RP, four significantly different clinical subtypes could be recognized, according to both age of onset and the pattern of development (P less than 0.001), namely cone-rod dystrophy and early-onset severe forms on the one hand (mean age of onset = 7.6 years), late-onset mild forms and senile forms on the other. Similarly, two significantly different clinical subtypes could be recognized in X-linked RP, according to both mode and age of onset, which were either myopia (mean age = 3.5 +/- 0.5 years) or night blindness (mean age = 10.6 +/- 4.1 years. P less than 0.001). By contrast, no difference was noted regarding the clinical course of the disease, which was remarkably severe whatever the clinical subtype (blindness before 25 years). In addition, all obligate carriers in our series were found to have either severe myopia or pigment deposits in their peripheral retina. Finally, sporadic RP represented the majority of cases in our series (42%). There was a considerable heterogeneity in this group, and at least three clinical forms could be recognized, namely cone rod dystrophy, early onset-severe forms and late onset moderate forms. At the beginning of the disease, the hereditary nature of the sporadic forms was very difficult to ascertain (especially between 7-10 years) and only the clinical course could possibly provide information regarding the mode of inheritance. However, the high level of consanguinity, and the high sex ratio in early onset and severe sporadic forms (including cone-rod dystrophy), was suggestive of an autosomal or X-linked recessive inheritance, while increased paternal age in late onset forms was suggestive of autosomal dominant mutations. PMID- 2227957 TI - Fragile X expression and X inactivation. I. The expression of the fragile site at Xq27.3 is not suppressed on inactive X chromosomes separated from the active homologue. AB - The inactive fragile X chromosomes of a 47,fra(X),fra(X),Y male with a typical fragile X phenotype were successfully separated from the active homologues by means of somatic cell hybridization. It was shown by FUdR-induction and caffein posttreatment that the separated inactive X chromosomes expressed their fragile sites and that the presence of an active mutated X chromosome was not a prerequisite for fragile X expression. The fragility seems to be an intrinsic property of the individual fragile site. This result is in favour of the classical concept that the fragile site at Xq27.3 has a primary pathogenetic function in this syndrome, although the fragility itself could represent a secondary phenomenon related to an unknown alteration of the DNA in this chromosome region. It is also concluded that inactivation of the fragile X chromosome in females is not responsible for either false negative fragile X findings or the observation of fragile X negative colonies isolated from fragile X positive fibroblasts in heterozygotes. PMID- 2227959 TI - An informative polymorphism detectable by polymerase chain reaction at the 3' end of dystrophin gene. PMID- 2227960 TI - Applying health promotion to seniors' dental health: the Toronto experience. PMID- 2227958 TI - A ZFY-negative 46,XX true hermaphrodite is positive for the Y pseudoautosomal boundary. AB - Two loci on the short arm of the human Y chromosome have recently been described as candidates for the testis determining factor (TDF); namely, ZFY, and a locus distal to ZFY, near the pseudoautosomal boundary. We have previously reported on seven 46,XX true hermaphrodites and one 45,X mixed gonadal dysgenesis case all presenting with testicular tissue in their gonads in the apparent absence of Y specific DNA sequences. A reanalysis of these cases shows them all to lack ZFY, but one 46,XX true hermaphrodite carries sequences next to the Y pseudoautosomal boundary. This case provides further evidence for assigning the TDF locus very close to the pseudoautosomal region on Yp. PMID- 2227961 TI - [In Tunisia: description of a health education program based on socio-cultural realities]. AB - Structured within the framework of the National Programme for the Fight Against Diarrhoea in Tunisia, (PNLAD) the goal of the LAD Project is to improve the understanding and in-home treatment of diarrhoea by mothers. The programme consists of three elements: education of the mothers through health centers and preschool institutions, training of health care and social workers, and a mass media campaign. This article discusses the education programme for mothers through preschool institutions. Before embarking on its education programme, the project team conducted a preliminary study in order to establish what level of knowledge of diarrhoea existed among the general population and what current treatment methods were used. The study consisted of small discussion groups composed of mothers, grandmothers, and fathers. In evaluating current notions regarding diarrhoea, the study noted the various vocabulary used and its meaning for both diarrhoea and dehydration. It also examined the general beliefs of what caused diarrhoea and what people believed would cure and/or prevent the disease. As far as treatment methods were concerned, it was important to understand the origins of the various remedies, the level of awareness of the formal and informal health channels that existed and the different kinds of treatment based on diet, mother's milk, liquids, saline/sugar solutions and medication. The second key aspect of the programme concerned the kind of educational materials and teaching methods used. Both had to be geared towards the teaching of adults while insuring a real exchange of knowledge and experience between the population and the development personnel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2227963 TI - The IUHE: "Vision 2000" a draft strategy. PMID- 2227962 TI - Strengthening the effects of schooling on health practices in Kenya. PMID- 2227965 TI - Health coverage in Indian English newspapers. PMID- 2227964 TI - Bottle-feeding: an already entrenched practice that needs active discouragement in developing communities. PMID- 2227966 TI - Media consultation on AIDS. PMID- 2227967 TI - Health for all by the year 2000: a challenge to behavioural sciences and health education. PMID- 2227968 TI - Vector quantization for compression of multichannel ECG. AB - We propose a scheme based on vector quantization (VQ) for the data-compression of multichannel ECG waveforms. N-channel ECG is first coded using m-AZTEC, a new, multichannel extension of the AZTEC algorithm. As in AZTEC, the waveform is approximated using only lines and slopes; however, in m-AZTEC, the N-channels are coded simultaneously into a sequence of N + 1 dimensional vectors, thus exploiting the correlation that exists across channels in the AZTEC duration parameter. Classified vector quantization (CVQ) of the m-AZTEC output is next performed to exploit the correlation in the other AZTEC parameter, namely, the value-parameter. CVQ preserves the waveform morphology by treating the lines and slopes as two perceptually-distinct classes. Both m-AZTEC and CVQ provide data compression and their performance improves as the number of channels increases. Moreover, the final output differs little from the AZTEC output and hence ought to enjoy the same acceptability. PMID- 2227969 TI - An approach to cardiac arrhythmia analysis using hidden Markov models. AB - This paper describes a new approach to ECG arrhythmia analysis based on "hidden Markov modeling" (HMM), a technique successfully used since the mid-1970's to model speech waveforms for automatic speech recognition. Many ventricular arrhythmias can be classified by detecting and analyzing QRS complexes and determining R-R intervals. Classification of supraventricular arrhythmias, however, often requires detection of the P wave in addition to the QRS complex. The hidden Markov modeling approach combines structural and statistical knowledge of the ECG signal in a single parametric model. Model parameters are estimated from training data using an iterative, maximum likelihood reestimation algorithm. Initial results suggest that this approach may provide improved supraventricular arrhythmia analysis through accurate representation of the entire beat including the P wave. PMID- 2227970 TI - Ventricular tachycardia and fibrillation detection by a sequential hypothesis testing algorithm. AB - An algorithm for detecting ventricular fibrillation (VF) and ventricular tachycardia (VT) by the method of sequential hypothesis testing is presented. The algorithm first generates a binary sequence by comparing the signal to a threshold. The probability distribution of the time intervals of the binary sequence is obtained, and Wald's sequential hypothesis testing procedure is next employed to discriminate the arrhythmias. Sequential hypothesis testing of 85 cases resulted in identification of 1) 97.64% VF and 97.65% VT episodes after 5 s, and 2) 100% identification of both VF and VT after 7 s. The desired false positive and false negative error probabilities can be preprogrammed into the algorithm. An important feature of the sequential method is that extra time for detection can be traded off for improved accuracy, and vice versa. PMID- 2227971 TI - Standardized evaluation of techniques for measuring the spectral compression of the myoelectric signal. AB - A digital algorithm was designed to produce band-limited noise with adjustable median frequency and amplitude. This algorithm produces test signals with spectral characteristics typical of those of the surface myoelectric signals encountered in muscle fatigue studies. These synthesized signals provide the basis for standardized evaluation of the performance of various techniques which monitor the spectral compression of the myoelectric signal during muscle fatigue. PMID- 2227972 TI - Simulation of propagation along a cylindrical bundle of cardiac tissue--I: Mathematical formulation. AB - This paper presents a mathematical description based on a three-dimensional model for studying propagation in cardiac muscle. The model makes use of the bidomain concept to construct a representation of a cylindrical, multicellular bundle lying in an extensive volume conductor. The equations for the cylindrical bidomain are derived here for different combinations of boundary conditions and simplifying assumptions. The analysis shows that an analytic model for propagation can be set up if one assumes that the ratio of the intracellular and interstitial bidomain conductivities in the radial and axial direction are the same (i.e., equal anisotropy) and the intracellular radial current density vanishes at the surface. The simulation of this model will be discussed in a subsequent paper. As a point of reference, the classical one-dimensional cable model is also examined and the expressions governing propagation are reformulated to account for the extracellular medium, a factor ignored in most simulation studies. PMID- 2227973 TI - Simulation of propagation along a cylindrical bundle of cardiac tissue--II: Results of simulation. AB - Previous evaluations of the cylindrical bidomain model of a bundle of cardiac tissue, have been obtained by using an analytic function for the transmembrane potential and assuming the activating wavefront through the bundle cross section is planar. In this paper, nonlinear membrane kinetics are introduced into the bidomain membrane and equal anisotropy ratios are assumed, permitting the transmembrane potential to be computed and its behavior examined at different depths in the bundle and for different values of conductivity and bundle diameters. In contrast with single fiber models, the bundle model reveals that the shape of the action potential is influenced by tissue resistivities. In addition, the steady-state activation wavefront through the cross-section perpendicular to the long axis of the bundle is not planar and propagates with a velocity that lies between that of a single fiber in an unbounded volume and a single fiber in a restricted extracellular space. In general, the bundle model is shown to be significantly better than the classical single fiber model in describing the behavior of real cardiac tissue. PMID- 2227974 TI - Evaluation of shoulder movement as a command control source. AB - The purpose of this study was to evaluate the use of scapular shoulder movement as a command control source. The focus of this study was on the evaluation of movement signals from quadriplegic subjects as well as on the processing of these signals for use as command inputs to a functional neuromuscular stimulation (FNS) hand-grasp system. The shoulder movement of three C5-level quadriplegic and nine normal subjects was studied using externally mounted two-degree-of-freedom transducers overlying the sternum and clavicles. The C5-level quadriplegic subjects tested had a considerably poorer range of motion than the normal subjects. The range of motion was greatest in elevation but was coupled with a significant component of retraction. The vertical command resolution of the quadriplegic subjects ranged from eight to 13 command levels, whereas the horizontal range contained four or fewer command levels. Normal subjects were able to produce 26 to 79 command levels along the vertical axis and 18 to 85 along the horizontal axis. Subjects were able to maintain a static command level to within several percent of their range in trials lasting from 10 to 30 s. The quadriplegic subjects performed poorly in tasks where they were required to move to a point along the horizontal or vertical central axis and then along the opposite axis. The normal subjects were readily able to perform these tasks. The interference with the command signal due to movement of the opposite extremity was significant, with a maximum error ranging between 25 and 86% along the vertical axis and between 38 and 105% along the horizontal axis. Rise time and normalized velocity (velocity divided by the size of the movement) were found to be suitable for distinguishing different types of shoulder movements independent of the size of the movement. Shoulder movement in quadriplegics is suitable as a command control source for a FNS hand-grasp system requiring one proportional command signal and at least one logical command signal with appropriate processing of the signals. The available transducers are cosmetically acceptable and are easy to don and doff. Use of shoulder movement as a command control source does not interfere with other activities of the user such as eating or talking. Shoulder movement also provides a command control source that is easy for the user to learn and provides some feedback to the user through shoulder proprioception. PMID- 2227975 TI - Restoring unassisted natural gait to paraplegics via functional neuromuscular stimulation: a computer simulation study. AB - Functional neuromuscular stimulation (FNS) of paralyzed muscles has enabled spinal-cord-injured patients to regain a semblance of lower-extremity control, for example to ambulate while relying heavily on the use of walkers. Given the limitations of FNS, specifically low muscle strengths, high rates of fatigue, and a limited ability to modulate muscle excitations, it remains unclear, however, whether FNS can be developed as a practical means to control the lower extremity musculature to restore aesthetic, unsupported gait to paraplegics. A computer simulation of FNS-assisted bipedal gait shows that it is difficult, but possible to attain undisturbed, level gait at normal speeds provided the electrically stimulated ankle plantarflexors exhibit either near-normal strengths or are augmented by an orthosis, and at least seven muscle-groups in each leg are stimulated. A combination of dynamic programming and an open-loop, trial-and error adjustment process was used to find a suboptimal set of discretely-varying muscle stimulation patterns needed for a 3-D, 8 degree-of-freedom dynamic model to sustain a step. An ankle-foot orthosis was found to be especially useful, as it helped to stabilize the stance leg and simplified the task of controlling the foot during swing. It is believed that the process of simulating natural gait with this model will serve to highlight difficulties to be expected during laboratory and clinical trials. PMID- 2227976 TI - An improved video-based computer tracking system for soft biomaterials testing. AB - We present an improved video-based computer system for on-line tracking of small markers moving in a plane. The system consists of a CCD camera, a video monitor, a dedicated 80386/20 microcomputer, a video frame grabber, and custom software. Up to four markers can be tracked at the 30-Hz video frame rate using a two-step, correlation-based search procedure. We discuss the requisite hardware and software requirements and illustrate how this tracking system can be used to collect strain data during biaxial stretching tests on planar soft tissues. Operating at 30 Hz, this system is an improvement over those previously reported, which are either slower or yield less information. PMID- 2227978 TI - Two requirements for job contentment: autonomy and social integration. AB - The interaction of autonomy (control over work activities) and social integration (relationships with co-workers) was investigated in a sample of newly employed nurses in the 6th and 12th month of work. Those nurses with low autonomy and low social integration reported low job satisfaction and work motivation, poor commitment to the organization and less intent to stay on the job. They were older, with more experience and more education and tended to work on medical units. This study supports the notion of feminist psychologists that what women nurses want is "autonomy with connectedness". PMID- 2227977 TI - An umbilical data-acquisition system for measuring pressures between the foot and shoe. AB - We have developed an umbilical data-acquisition system for measuring pressures between the foot and shoe during walking. It consists of pressure sensors in the insoles of shoes, amplifier circuits, umbilical cables, an analog-to-digital converter, and a graphics display card in an IBM PC for real-time data collection and display. The applied pressure on a sensor decreases its resistance, which causes the output voltage of the amplifier circuit to increase. We attach seven sensors to the surface of each insole of a pair of extra-depth shoes and calibrate all the sensors in the insole before and after each test using a load cell as a reference. The IBM PC samples the outputs from the sensor and the load cell and stores a piecewise linear lookup table for use in compensation for the nonlinearity of the sensor. On the PC's graphics display, two programs provide displays of foot pressures as real-time bar graphs or as analog pressure versus time curves. PMID- 2227979 TI - Wife rape in a sample of psychiatric patients. AB - A descriptive study of 53 ever-married women currently being treated for primary depression or anxiety documented that wife rape is a significant negative factor in the lives of these women and is positively correlated with a history of childhood sexual abuse. The study identified the incidence of wife rape in this sample and described co-variables of the wife rape experience. The findings from this research may be used by nurses to increase the effectiveness of their care. PMID- 2227981 TI - Passage through infertility treatment: a stage theory. AB - This grounded theory study explored the perceptions of 25 couples as they underwent infertility assessment and treatment. A substantive theory of passage through infertility treatment explains the psychosocial responses of couples to their infertility from prediagnosis to posttreatment. The theory consists of three concepts--engagement, immersion and disengagement. Eight stages were identified within these concepts: experiencing a dawning of awareness, facing a new reality, having hope and determination, intensifying treatment, spiralling down, letting go, quitting and moving out, and shifting the focus. PMID- 2227980 TI - Overadherence with breast self-examination recommendations. AB - Overadherence with breast self-examination (BSE) was studied to seek explanations for this phenomenon and to suggest individualized interventions for the performance of BSE. In a descriptive study, women attending BSE instruction (N = 264) were interviewed regarding their beliefs as well as peer and professional interactions about breast self-examination. Of these women, 29 (11%) were overadherent; they had the highest rates of breast disease and the least professional instruction and encouragement for BSE. Ironically, some women perform BSE repeatedly because they lack sufficient knowledge and confidence. Clinicians should assess women's knowledge of BSE as well as their skill to provide individualized clarification. PMID- 2227982 TI - Impact of work stress on female nurse educators. AB - Factors predictive of work-related stress in 287 female nurse educators were studied in a randomly selected sample of 18 U.S. (NLN) accredited schools of nursing. The Maslach Burnout Inventory-Form Ed, the Hardiness of Personality Inventory, the Blair Exercise Activity Index, a demographic tool and an administrator-completed questionnaire were used. Moderate levels of stress were found to exist, with five individual variables (hardiness, age, education, years in nursing education and exercise) and five organizational variables (student contact hours for part-time faculty, task complexity, economic environment of school, number of full-time faculty and percentage of tenured faculty) combining to best predict the occurrence of work-related stress. PMID- 2227983 TI - Critical multiplism: a research strategy for nursing science. AB - This paper describes critical multiplism from the perspective of the world views and models of scientific inquiry that frequently guide the work of nurse scientists. Nurse scientists may wish to consider critical multiplism as a research strategy within a dialectical model of scientific inquiry to study the multiple realities of interest to nurses. This approach to nursing knowledge development may enhance the usefulness of nursing research findings in nursing practice. PMID- 2227984 TI - The metalanguage of menopause research. AB - Nurse scholars often debate such technical issues as when to use quantitative or qualitative methods or some combination of methods. The proper focus of a discussion on nursing science should be the basic assumptions and values of various approaches to research. Unless we gain an awareness and appreciation of the human process of knowledge generation, our research questions will remain limited, and nursing practice will be shaped in ways that may be neither coherent nor consistent with our philosophies of nursing. Used to demonstrate this position, is the knowledge of menopause gleaned through a philosophical inquiry of the biomedical and sociocultural approaches to menopause research. PMID- 2227985 TI - Preventive intervention following accidental death of a child. AB - This paper describes the development and pilot testing of an empirically and theoretically based preventive intervention program for bereaved parents whose adolescent and young adult children died suddenly following an accident. The parents were assigned to either an early (2-6 months postloss) or a later (7-13 months postloss) transition group (N = 15) in which they received two-dimensional preventive intervention: informational support and emotional support. A comparison group (N = 19) received no intervention. Weekly and summative evaluations completed by bereaved parents and group leaders showed the therapeutic benefits of the preventive intervention for both treated groups. However, the two groups responded differently to the interventions, suggesting that timing and type of support might both be important factors to consider. PMID- 2227986 TI - Openness: a qualitative analysis of nurses' and patients' experiences of therapeutic touch. AB - The constant comparative method was used to generate a grounded theory explaining the process of therapeutic touch for seven nurses and seven patients. Interviews and observations of one treatment session each indicate that the primary experience of therapeutic touch is opening to the flow of the universal life energy. This includes three major categories of experience: (a) opening intent- allowing oneself to focus on getting the universal life energy moving again; (b) opening sensitivity--assessing the quality of its flow; and (c) opening communication--participating in a healing relationship that unblocks, engages and enlivens its movement. Further research on therapeutic touch using qualitative methodology may deepen our understanding of the inner experiences of both patients and nurses to experiences that facilitate the healing process. PMID- 2227987 TI - Subjectively perceived quality of life. AB - Subjectively perceived quality of life is a priority concern in planning, implementing and evaluating health policy and treatment decisions. The lack of a universally accepted definition of this multivariate concept is a barrier to sound research. This article analyzes the concept of subjectively perceived quality of life to determine its critical attributes, antecedents and consequences to establish a basis for an operational definition for use in research. PMID- 2227988 TI - Functional status during pregnancy and the postpartum: a framework for research. PMID- 2227990 TI - A nursing model for homeless families. PMID- 2227989 TI - Nightingale, nursing and harassment. PMID- 2227991 TI - Presence of host-reactive and MHC-restricted T cells in a transplanted severe combined immunodeficient (SCID) patient suggest positive selection and absence of clonal deletion. PMID- 2227992 TI - Tolerance in vivo and in vitro. PMID- 2227993 TI - Imprint of thymic selection on autoreactive repertoires. AB - We have focussed on the differences in origin and physiological properties of two classes of self-reactive T cells. Autoreactive T cells described in many laboratories are activated in the course of normal immune responses to foreign antigen. These T cells can be shown under well-defined conditions to be the direct progeny of antigen-stimulated precursors. This, together with evidence that their activation requirements can be distinguished from those of antigen specific, MHC-restricted T cells, leads us to suggest that they represent a particular physiological state that recapitulates the conditions of thymic selection and is induced in many antigen-specific, MHC-restricted peripheral T cells as a result of normal antigen-dependent activation. Although it appears that the associated physiological properties can be stable in some in vitro maintained lines, it is possible that this is normally a transient state in vivo. Available evidence concerning the specificity of these T cells indicates only that they can be activated in the absence of any identifiable foreign antigen by class II MHC-syngeneic but not MHC-allogeneic stimulators. We have suggested that such T cells are specific for the same elements, possibly an association of MHC and other self-peptides (Singer et al. 1987), that are the basis for positive selection in the thymus. The properties of these autoreactive T cells need to be distinguished from those of T cells associated with autoimmune pathology. It is presumed that autoimmune T cells are directly activated in a resting state by specific self-peptides. Our interest in distinguishing these self-reactive T-cell populations has focussed on different predictions concerning the diversity of their associated self-reactive repertoires. The relative complexity of the immune repertoire expressed in autoreactive T cells expanded by positive selection and restimulated in the course of normal antigen-specific immune responses should be considerably greater than that of autoimmune T cells constrained by negative selection and a narrow window of escape from self-tolerance. We were greatly hindered in our initial efforts in this analysis by the considerable effort required to characterize any specific immune repertoire. A published technique employing poly(A) tailing (Frohman et al. 1988) did not work efficiently in our hands, although others (Loh et al. 1989) have apparently had some success. We describe above an alternative approach, linker-facilitated PCR, which we have employed for efficient repertoire analysis. Using this method we have been able to identify dominant utilization of the Va4 family in T cells specific for the synthetic peptide YYEELLKYYEELLK.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2227995 TI - Images of caring. My day with Helen. PMID- 2227994 TI - Autoreactive HLA-DR-specific autoreactive T-cell clones: possible regulatory function for B lymphocytes and hematopoietic precursors. AB - The physiological significance of autoreactive T cells derived from normal individuals and activated in the absence of any identifiable foreign antigen by class II MHC-syngeneic molecules remains unexplained. Here we report that autoreactive T-cell clones (Tilkin et al. 1987) proliferate and are able to kill autologous or syngeneic EBV-cell lines but not autologous or syngeneic HLA-Class II-positive PHA-activated T-cell blasts. Furthermore, they are able to efficiently inhibit in vitro the differentiation of CFU-GM and BFU-E colonies, in agreement with the well-known observation that hematopoietic precursors express HLA-DR molecules (Cannistra et al. 1986). The reasons why the autoreactive clones do not recognize T-cell blasts, as well as their possible implications in regulatory mechanisms involving HLA-class II molecules are discussed. PMID- 2227996 TI - ECMO therapy. PMID- 2227997 TI - Your personal business. Planning for your retirement. PMID- 2227998 TI - Orthopaedic nursing: nursing is the operative word. PMID- 2227999 TI - The use of physical restraints for the elderly. PMID- 2228000 TI - The future of gerontic nursing. PMID- 2228001 TI - How did this happen to your little boy? PMID- 2228004 TI - The future of pediatric nursing: anticipating the health care needs of children. PMID- 2228002 TI - Perceptions from the nursing home: how we can make a difference. PMID- 2228003 TI - Understanding the psychosocial challenges of older adulthood. PMID- 2228005 TI - The arts: helping children cope with hospitalization. PMID- 2228006 TI - What do I say when a baby is born with a birth defect? PMID- 2228008 TI - Ethics in nursing education: reexamining the need. PMID- 2228007 TI - Solutions to the nursing shortage. Second place winner--NSNA/Johnson & Johnson Consumer Products Essay Contest. PMID- 2228009 TI - A case control study of cancer cervix patients attending Command Hospital, Pune. AB - A case control study was undertaken with the objective to determine the association of certain host factors like marital status, age at first marriage, duration of married life, parity, literary status and genital hygiene, in the subsequent development of cancer cervix. A total number of ninety-two cases and an equal number of control subjects, under matched case control design, were studied at Command Hospital, Pune over a period of nine months. Salient findings of this epidemiological study have been highlighted in this communication. Few of the risk factors viz early age at first marriage, longer duration of married life, increased and early parity, low educational status and poor genital hygiene were found to have played significant role in the subsequent development of carcinoma cervix. PMID- 2228010 TI - Histopathological changes following anterior chemotherapy in advanced breast cancer. AB - Twenty five patients of advanced breast cancer (Stage IIIb and IV) were studied and the histological changes following chemotherapy were looked. All the tumours showed varying degree of histological changes. Twenty eight percent tumours showed Grade I changes, 28 percent had Grade II changes and 28 percent had Grade III changes. Residual tumour was present in all the cases. The tumour showing higher grade of cancer cell degeneration following chemotherapy had better response. Seven tumours showing Grade III changes had 85.7 percent partial response. No complete response was achieved. PMID- 2228011 TI - Adenolymphoma of lacrimal sac. A case report. PMID- 2228012 TI - Calcified hypernephroma. A case report. AB - Pattern of classification in an renal neoplasm is variable. If calcium is located nonperipherally (within the mass) it is more likely to be a renal cell carcinoma. But peripheral calcification does not rule out malignancy. PMID- 2228013 TI - Non functioning kidney in renal cell carcinoma. Case report of an unusual cause. PMID- 2228014 TI - Coagulant and fibrinolytic activities of a metastasising and non-metastasising tumour line. AB - The two types of transplantable methyl cholanthrene induced fibrosarcoma in rats was used to find out the possible relationship between the fibrinolytic, procoagulant activities and the metastasizing capacity of the tumours. The highly metastatic tumour seems to possess high fibrinolytic activity as compared to the low metastatic one. Interestingly enough, it was found that the procoagulant and fibrinolytic activities in the highly metastasising tumour bear inverse relationship with each other in relation to time of tumour growth. The procoagulant activity of the tumour bypasses factor VII and acts at factor X level. The plasminogen activator present in the tumour tissue has been characterized by sephadex G-200 column chromatography and PAGE. PMID- 2228015 TI - Cancer projection by the turn of century-Indian science. AB - This is an attempt to understand the magnitude of cancer problem in India. The incidence data generated by the three population based cancer registries at Bangalore, Bombay and Madras and the population projections of country have been utilised for estimating the present and future load of new cancer cases. It is estimated that the total number of incident cases in males increased from 0.29 million to 0.43 million by the turn of the century as a result of change in size and composition of population and when adjusted for tobacco habits the estimates increased to 0.49 million. In females the incident cases of cancer for three registries increased from 0.32 to 0.42 million by 2001, with cancer of uterine cervix and breast being the major problems. The above results show an urgent need for strengthening and augmenting the existing diagnostic/treatment facilities which are vow fully inadequate to tackle even the present load. PMID- 2228016 TI - Secondary carcinoma of testis--a clinicopathologic study of 10 cases. AB - Ten cases of metastatic carcinomas to the testis are recorded in the last 17 years from Tata Memorial Hospital (TMH). There were two from kidney and four each from prostate and gastrointestinal tract carcinomas. The age of the patients ranged from 40 to 82 years with a mean of 57 years. The disease was unilateral in eight cases and bilateral in two. The testicular mass preceded the symptomatology of the primary lesion in a single case. The disease was an incidental finding in three prostatic carcinomas, where bilateral orchidectomy was performed as a therapeutic procedure. Hydrocele was associated in three cases. Grossly the tumour deposits were nodular or diffuse. Microscopically involvement of the interstitial parenchyma, with sparing of the tubular structures of the testis, epididymis and retetestis and special stains for mucin were helpful in the diagnosis. Lymphatic emboli were present in six cases and vascular emboli in three. The spermatic cord was involved in two cases. PMID- 2228017 TI - Pediatric cancer care in India. A national survey. AB - A national survey of institutions treating children with cancer was undertaken in April 1988. The 21-item questionnaire included questions on personnel, treatment facilities, support services, attitudes and opinions regarding pediatric cancer care. 73 institutions responded. From the survey, it emerged that pediatricians did not see all pediatric patients with cancer at one-third of the respondent institutions. 50 percent of cancer centres did not have pediatricians. Cancer centres were better staffed with specialist personnel and better support services. Respondents felt that pediatric oncologists and specialist support personnel were necessary for optimal pediatric cancer care and facilities at medical colleges needed to be improved because of the large number of children with cancer treated at these institutions. PMID- 2228018 TI - Activation of idiotype-specific CD4+ T-cell line: cellular processing of exogenous self-immunoglobulin. AB - An idiotype (Id)-specific long-term cultured T-cell line has been generated from BALB/c mice immunized with M315 (alpha, lambda 2). The cell line comprises both CD3+ and CD4+ but CD8- cells. The T-cell line is stimulated in a class II major histocompatibility complex (MHC)-restricted manner, and is capable of producing interleukin-2 (IL-2) in response to the Id along with Iad-bearing antigen presenting cells (APC). Fine Id specificity analysis has shown that changes in amino acid residues, Phe-94, Arg-95 and Asn-96, located on the VL-315, resulting from a somatic mutation mechanism of the mouse V lambda 2 gene, contribute to the T-cell activation. Pretreatment of APC with either glutaraldehyde or paraformaldehyde prevented both Fv-315 and VL-315 from triggering the T cells. This suggested that further processing of VL is required for T-cell activation. To clarify this point, we have generated a synthetic peptide, designated P18, which spans residues 91-108 of VL-315. In sharp contrast to VL, prefixed APC were capable of presenting P18 to stimulate the T-cell line to induce IL-2. PMID- 2228019 TI - Effects of cyclosporin A on T-cell development in organ-cultured foetal thymus. AB - The effects of cyclosporin A (CsA) on T-cell development were assessed in an organ culture of murine foetal thymus. Applying three-colour flow cytometric analysis, we showed that the agent inhibits the development of mature CD3/T-cell receptor alpha beta (TcR alpha beta)+ cells both in CD4+8- and CD4-8+ populations. CD4-8- cells appeared to be accumulated by CsA. We examined the heterogeneity of CD4-8- cells generated in the organ culture, and defined five subpopulations by the expression of the cell-surface molecules CD3/TcR, J11d and CD25. It has been demonstrated that only the CD3/TcR alpha beta+ J11d- CD25- subpopulation is susceptible to the suppressive effects of CsA among CD4-8- cells, whereas all the other four subpopulations, including CD3/TcR gamma delta+ cells, are resistant. Thus, all of the TcR alpha beta-bearing cells, including CD4-8- cells but none of the TcR alpha beta- cells, are CsA sensitive. Because it is known that CsA inhibits the TcR-mediated signalling events in mature T cells and that signallings mediated via the interaction of TcR with major histocompatibility complex (MHC) molecules on thymic stroma cells are crucial for thymic selection of T cells, these results indicate that TcR alpha beta-bearing CD4-8- cells but not TcR gamma delta-bearing CD4-8- cells undergo thymic positive selection. PMID- 2228020 TI - Mechanisms of inhibition of mononuclear cell activation by the iron-chelating agent desferrioxamine. AB - Iron-withholding by the chelating agent desferrioxamine abrogates the proliferative response of human peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA). The present study investigated whether desferrioxamine operates late in the activation process or, as recently suggested, at an early stage, by inhibiting the appearance of the interleukin-2 (IL-2) receptor. Human PBMC were stimulated with PHA (10 micrograms/ml) and [3H]thymidine ([3H]TdR) incorporation determined after 66 hr of culture. Greater than 90% inhibition was achieved by concentrations of desferrioxamine as low as 5 mumol/l present throughout culture, while IL-2 receptor expression (anti-Tac), analysed by FACS, was maintained at up to 75% of control levels. 300 mumol/l desferrioxamine present throughout culture abrogated [3H]TdR incorporation and additionally suppressed IL-2 receptor to 10-15% of control levels. In contrast, the same high dose of desferrioxamine when added for 2 hr to cells previously cultured for 66 hr produced 80% inhibition of [3H]TdR incorporation but failed to inhibit expression of the IL-2 receptor. Desferrioxamine rapidly achieved equilibrium across the cell membrane (within 60 min) and chelated 59Fe delivered to activated cells by the transferrin endocytic cycle. These results indicate that desferrioxamine can inhibit T-cell activation either early or late in the process by chelating iron and independently of an effect on the IL-2 receptor. In support of a dual effect of the drug is the finding that at 50 mumol/l, desferrioxamine enhanced expression of the transferrin receptor occurred, an adaptive response made to intracellular iron depletion, while IL-2 receptor expression was inhibited. PMID- 2228021 TI - Evidence of a role for TNF-alpha in cytolysis by CD4+, class II MHC-restricted cytotoxic T cells. AB - Variants of the tumour necrosis factor (TNF)-sensitive cell lines BALB/c 3T3 and WEHI-164/13 were generated by selection in high concentrations of recombinant TNF alpha. The selected cells were highly resistant to cytolysis by both TNF-alpha and TNF-beta (lymphotoxin); however, there was no significant difference in sensitivity to killing by class I major histocompatibility complex (MHC) restricted cytotoxic T lymphocytes (CTL). Resistance to TNF-mediated lysis was, however, accompanied by increased resistance to cytolysis by CD4+ class II restricted CTL. Furthermore, cytolysis of WEHI-164/13 cells by CD4+ was completely inhibited by anti-TNF antiserum. These data strongly suggest a role for TNF in killing by CD4+ class II MHC-restricted CTL but not in class I MHC restricted killing. PMID- 2228023 TI - The distribution of immunoreactive interferon-alpha in formalin-fixed paraffin embedded normal human foetal and infant tissues. AB - Human foetal and infant tissues were studied to test the hypothesis that microbes have a role in switching on interferon-alpha (IFN-alpha) synthesis. Foetal tissues were essentially 'germ free', while the infants had been exposed to a normal microbial environment in life. IFN-alpha was first seen at 9 weeks gestation in macrophages in the liver and thereafter was seen in macrophages in most other organs. When infant lungs were compared with foetal lungs, a statistically significant increase in the number of macrophages and the percentage of these cells expressing IFN-alpha was noted in the infant lungs. No such change was observed in spleen, liver and thymus following birth. These findings suggest that there is a basal production of IFN-alpha by macrophages that is not dependent on microbial products, but that such products can enhance synthesis of this cytokine. PMID- 2228022 TI - Generation and characterization of a neutralizing rat anti-rmTNF-alpha monoclonal antibody. AB - A rat anti-recombinant mouse tumour necrosis factor-alpha (rmTNF-alpha) monoclonal IgM antibody (1F3F3) with high specific binding activity for rmTNF alpha was generated. The 1F3F3 monoclonal antibody (mAb) neutralizes the cytotoxic activity in vitro of rmTNF-alpha on L929 cells and inhibits the binding of radiolabelled rmTNF-alpha to its putative receptor on L929 cells. The 1F3F3 mAb binds to monomeric, dimeric and trimeric rmTNF-alpha and does not bind to reduced rmTNF-alpha, indicating that the recognized epitope is sensitive to denaturation. Using the 1F3F3 mAb as a capturing antibody and a biotinylated anti rTNF-alpha as a detecting antibody, we have developed a sandwich ELISA that can specifically detect biologically active mTNF-alpha with a detection limit of 10 pg mTNF-alpha/well. This assay correlates well with the classical L929 cristal violet assay for the detection of bioactive rmTNF-alpha in biological fluids. The 1F3F3 mAb inhibits various in vitro biological activities of the rmTNF-alpha, such as the TNF-alpha-mediated tumoricidal activity of activated macrophages, the rmTNF-alpha-dependent stimulation of neutrophil degranulation and the growth promoting effect of rmTNF-alpha. In vivo the 1F3F3 mAb inhibits lipopolysaccharide (LPS)-induced endotoxic shock. In conclusion, the 1F3F3 mAb is a useful tool to probe rmTNF-alpha activity both in vitro and in vivo. PMID- 2228024 TI - Thrombin and factor Xa enhance the production of interleukin-1. AB - Interleukin-1 (IL-1) plays a major role in inflammatory responses. Activation of coagulation and fibrin deposition typical of these reactions is mediated by macrophage procoagulants induced on stimulated macrophages. IL-1 activity in the supernatant of lipopolysaccharide (LPS)-stimulated guinea-pig macrophages was markedly enhanced by the presence of thrombin during macrophage activation. Although thrombin alone had no effect, inclusion of 1 mU/ml of thrombin with suboptimal levels of LPS produced a 200-fold increase in IL-1 activity, and further enhancement was observed with increasing doses of thrombin. The active site of thrombin was necessary for enhancement, as the serine esterase inhibitor di-isopropyl-fluorophosphate (DIP) and hirudin inhibited the synergy observed with LPS and thrombin. Prothrombin and Factor Xa also enhanced IL-1 production, although not to the same extent as thrombin. Factor Xa-like activity was demonstrated on the surface of LPS-stimulated macrophages. Both the Xa-like activity and IL-1 generated by LPS-stimulated cells were inhibited by heparin. Heparin with a high affinity for antithrombin III (anti-coagulant heparin; HAH) inhibited IL-1 generation, whereas low-affinity heparin (non-anticoagulant; LAH) had no effect. We show that proteases of the extrinsic coagulation cascade enhance IL-1 generation and propose that a Factor Xa-like activity present in activated macrophages, together with thrombin, may be important in IL-1 processing. PMID- 2228025 TI - A limited role of IL-1 in immune-enhancement by adjuvants. AB - Generation of interleukin-1 (IL-1) in the draining lymph nodes after injection of complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA) and alum was studied in line with IL-1 mRNA expression (cytoplasmic slot blot analysis) and IL 1 beta antigen detection (ELISA and immunohistochemistry) in rabbits. The expression of IL-1 beta mRNA was marked from 6 to 96 hr, with a maximum at around 24 hr post-injection of CFA, while injection of the other two adjuvants elicited only a moderate or negligible response. On the other hand, IL-1 alpha mRNA expression was almost negligible during the entire 8-week observation period after injection of the above three adjuvants. Generation of IL-1 beta antigen in the draining lymph nodes after CFA injection paralleled the expression of IL-1 beta mRNA. Immunohistochemistry revealed that cells containing IL-1 beta resided in the medullary sinuses, marginal sinuses and para-cortical area, but not in the follicles. Despite marked generation of IL-1 beta in CFA-treated draining lymph nodes, the primary antibody response (IgG) to ovalbumin differed only slightly between the three animal groups that were immunized with the antigen incorporated in CFA, IFA and alum. Further, rIL-1 beta did not significantly enhance the immune response when it was entrapped together with the antigen in IFA and alum. IL-1 beta enhanced the immune response only when it was injected with antigen without adjuvant. Thus, IL-1 seemed to play only a limited role, if any, in the augmentation of the primary immune response by the above-mentioned adjuvants. PMID- 2228026 TI - IL-5 enhances the in vitro adhesion of human eosinophils, but not neutrophils, in a leucocyte integrin (CD11/18)-dependent manner. AB - In an attempt to explain the preferential accumulation of eosinophils at sites of allergic tissue reactions, we have studied the effects of interleukin-5 (IL-5) on the adherence of human eosinophils and neutrophils to plasma-coated glass (PCG) or human microvascular endothelial cells (HMVEC). IL-5 was compared with IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and platelet-activating factor (PAF), since all these agents have biological properties associated with eosinophil activation and/or survival in vitro. IL-5, IL-3 and GM-CSF induced a time-dependent increase in adherence of normal density eosinophils to PCG optimal at 60 min, whereas the effect of PAF was greater at 15 min. Similar results were obtained with neutrophils, with the exception that IL-5 had minimal and non significant effects on this cell type. Unstimulated eosinophils and neutrophils also adhered to PCG or HMVEC, but in low numbers. Preincubation of eosinophils with IL-5, GM-CSF or PAF resulted in dose-dependent increases in the numbers of adherent cells to PCG. IL-3 had a smaller but significant effect on enhanced eosinophil adhesion to PCG, while IL-2 and lyso-PAF were ineffective. Neutrophils gave similar levels of baseline and stimulated adhesion to PCG as eosinophils, IL 5 again had no significant stimulatory effect. IL-5 also increased eosinophil, but not neutrophil, adherence to HMVEC in a concentration-dependent manner. Preincubation with the protein synthesis inhibitor cycloheximide had no effect on IL-5-, GM-CSF- or PAF-stimulated eosinophil adhesion. The contribution of the CD11/18 leucocyte integrins to IL-5- and PAF-induced eosinophil hyperadherence was investigated by inhibition experiments utilizing monoclonal antibodies (mAb). Enhanced adhesion to PCG (by PAF) or HMVEC (by IL-5) was inhibited by (ranked in order of potency) anti-CR3 alpha = common beta-chain greater than LFA-1 alpha. Anti-p150,95 alpha had no measurable effect. Baseline adhesion by unstimulated eosinophils was not significantly influenced by prior incubation with these mAb. Using flow cytometry, IL-5 and IL-3 were found to up-regulate cosinophil but not neutrophil CR3 expression. These findings demonstrate that IL-5 enhances cosinophil, but not neutrophil, adherence reactions, by a mechanism dependent, at least in part, on the CD11/18 family of adhesion glycoproteins. PMID- 2228027 TI - Production of bovine immunoregulatory molecules by xenogeneic hybrids. AB - The study of bovine cytokines and lymphocyte surface markers has been restricted by the lack of stable, long-lived, easily maintained cell lines. To address this problem, bovine mononuclear leucocytes were fused with the mouse thymoma cell line BW5147 to produce interspecies hybrid cell lines and clones. Hybridomas were produced which contained more than 40 chromosomes and expressed one or more bovine leucocyte surface markers, they grew well and were cloned without the use of exogenous factors. Fusion rates were improved when exogenous factors, including recombinant human interleukin-2 (rhIL-2), were added. Some hybrids secreted immunoregulatory factors able to maintain the growth of either an IL-2 dependent bovine T-cell line (C625) and/or preactivated normal bovine B cells. Anti-human IL-2 partially blocked the T-cell growth factor (TCGF) activity produced by these hybrids. The release of growth factors by the hybrid clones 5/AA6/16 and 5/AA6/19 was augmented by concanavalin A stimulation. PMID- 2228029 TI - Biochemical manifestations of a rat mammary adenocarcinoma-producing cachexia: in vivo and in vitro studies. AB - The physical and metabolic characteristics of a Dark Agouti rat mammary adenocarcinoma and its effects on host metabolism are described. The tumour was characterized by a lack of glandular differentiation, tetraploidy, a rapid mitotic index and a high rate of glycolysis. The adenocarcinoma was readily maintained in tissue culture and could be passaged through the host by inoculating either cell suspensions or tissue explants. In the rat, tumour growth resulted in a loss of adipose tissue at a tumour mass of less than 5% body weight indicating that increased energy expenditure was already present at that stage. In addition the tumour caused anaemia, hypercalcaemia and hypoglycaemia. Hyperketonaemia was also observed in fasted tumour-bearing rats. Methotrexate arrested tumour growth in vivo. These aspects of the tumour model make it useful for investigations into host-tumour competition and mechanisms of cachexia. PMID- 2228030 TI - Lymphocyte activation as measured by interleukin-2 receptor expression to gluten fraction 111 in coeliac disease. AB - Lymphocyte activation was examined by interleukin-2 (IL-2) receptor expression on peripheral blood mononuclear cells from coeliac and control subjects. Purified T cells were incubated with gluten fraction 111 (a known toxic peptide for coeliac subjects), soyabean hydrolysate (an unrelated hydrolysed food antigen), and Concanavalin-A (Con-A, a non-specific mitogen). After 1-5 days incubation, expression of IL-2 receptors was assessed using a cellular enzyme-linked immunosorbent assay (ELISA). Gluten fraction 111 induced expression of IL-2 receptors on T lymphocytes from coeliac but not from normal subjects (P = 0.0005), whereas soyabean hydrolysate did not induce IL-2 receptor expression. Lymphocytes from both coeliac and normal subjects had similar increased IL-2 receptor expression after incubation with Con-A. Flow cytometry was also used to confirm specific expression of IL-2 receptor expression of lymphocytes from coeliac subjects. Interleukin-2 receptor expression increased from 0 to 5.4% of cultured mononuclear cells after 7 days incubation with gluten fraction III. These cells were CD3-positive and CD4-positive. We conclude that peripheral blood lymphocytes from coeliac subjects are sensitized specifically to gluten fraction III. PMID- 2228028 TI - Complement gene expression in hepatic and extrahepatic tissues of NZB and NZB x W (F1) mouse strains. AB - To study the role of local production of complement proteins during the evolution of a naturally occurring immune complex disease, C3, C4, C2 and Factor B mRNA expression was assessed in several tissues of the inbred mouse strains NZB and (NZB x W) F1 hybrid. In the NZB/W F1 hybrid strain, coincident with the development of glomerulonephritis a marked increase in kidney C3 and C4 mRNA was observed; Factor B mRNA, which is expressed as a doublet in kidney and intestine, showed an increase in expression of the smaller transcript. This alteration of kidney C3, C4 and Factor B mRNA is identical to that noted in association with lupus nephritis in the MRL lpr/lpr strain and following in vivo administration of endotoxin to the BALB/c strain. The development of systemic lupus erythematosis (SLE) in the NZB/W F1 was not associated with a marked change in hepatic complement gene expression. These findings support the hypothesis that local production of complement may play a role in the pathogenesis of glomerulonephritis and other tissue injury in SLE. PMID- 2228031 TI - Presentation of Salmonella antigens by peritoneal cells of normal and Salmonella infected mice. AB - A comparison of the ability of normal peritoneal cells (PC) and those harvested from mice 1-3 days after intraperitoneal immunization with live Salmonella enteritidis 11RX (11RX) to present antigen to 11RX-primed T cells was made using formalin-killed 11RX and a soluble 11RX antigen extract as antigens. Unfractionated PC and the adherent and non-adherent PC populations were analysed separately and the effects of the lysosomal function-impairing drug chloroquine and the fixative paraformaldehyde, used before or after antigen-pulsing, were also determined. The results presented indicate that immunization with live 11RX did not induce any detectable modulation of APC function which could account for the ability of live 11RX to induce cell-mediated immune responses involving Lyt 2+ T cells. PMID- 2228032 TI - An immunodominant antigen of Candida albicans shows homology to the enzyme enolase. AB - Antibody to an immunodominant antigen of approximately 48 kDa is found in a high proportion of patients with mucocutaneous or systemic infections of the yeast Candida albicans. A cDNA encoding part of the 48 kDa antigen has been isolated. From the deduced amino acid sequence of the cDNA clone, the 48 kDa antigen shows homology to the enzyme enolase. PMID- 2228033 TI - Murine candidiasis: susceptibility is associated with the induction of T cell mediated, strain-specific autoreactivity. AB - Inbred mice can be classified as susceptible or resistant to systemic infection with the yeast Candida albicans by histopathological evaluation of tissue lesions. Candida-specific memory T cell responses generated by resistant BALB/c mice are vigorous and sustained, whereas those displayed by susceptible CBA/H mice are weak. When spleen cells from immune mice were activated by culture with candida antigens in vitro, and injected into syngeneic and allogeneic recipients in the absence of further antigenic stimulation, cells from CBA/H mice induced a specific inflammatory response only in CBA/H recipients. In contrast, cells from immune BALB/c mice showed no specific activity. The effector cells were identified as T cells of the cytotoxic/suppressor subclass (CD4-, CD8+); and analysis in various F1 hybrid mice showed that reactivity was expressed only in animals carrying CBA/H genes. The data thus indicate that susceptibility to C. albicans infection is associated with the induction of a T cell subpopulation that has the potential to react specifically against unmodified self antigens expressed by the susceptible strain. PMID- 2228034 TI - [A critical review of the results of clinical experimentation with topical minoxidil 2%]. AB - The results of clinical double-blind trials using minoxidil 2% demonstrate the real efficacy of the drug in producing satisfactory esthetical results in some 30% of treated patients. One aspect of the results of this research which is not yet clear is the significant increase in the number of hairs, also found in voluntary subjects treated with placebo. In the present study is hypothesised that this increase may be partially explained by the failure to take into account the physiological seasonal variations in hair density, and by the confusion caused by the use of the "non-vello" category which is used to describe terminal (thick) and indeterminate (thin) hairs. In our study placebo failed to produce a significant increase in the number of terminal hairs, thus explaining why, even in the presence of an increased number of "non-vello" hairs, on average there was no real cosmetic benefit in these subjects. PMID- 2228035 TI - [Results of a preliminary study of 50 patients treated with a new corticosteroid: tipredane cream 0.1%]. PMID- 2228036 TI - [A clinical study on the use of norfloxacin in the therapy of urethritis caused by Chlamydia trachomatis]. AB - Norfloxacin (NOR) was given to 37 patients affected by urethritis due to Chlamydia trachomatis (CT), as demonstrated by clinical findings and fluorescent monoclonal antibody in urethral swab. The patients were divided into two groups according to a randomization list, and given either: NOR 400 mg t.i.d. or NOR 800 mg b.i.d. for 10 days. The 2 groups were comparable in terms of age, clinical presentation and duration of symptoms. Six out of 18 patients treated by regimen 2 had persistence of CT at the end of treatment (2 cases were clinically improved), while 4 out of 19 patients in group 1 dit not respond to the treatment. Overall 12 patients in group 2 (66.6%) and 15 patients in group 1 (79%) were asymptomatic and negative for fluorescent antibody at the end of the treatment. Both regimens were well tolerated. Our data show that NOR given at dosage higher than those usually recommended (e.g. 400 mg b.i.d.), may be of value for the treatment of urethritis due to Chlamydia trachomatis. PMID- 2228038 TI - [Determination of circulating antibodies in cutaneous leishmaniasis by immunofluorescence test]. AB - Using a gradient purified leishmania donovani infantum antigen, the sensitivity and specificity of the IIF test in detecting anti-leishmania antibodies are investigated. The "purified" antigen increases the specificity and sensitivity of the IIF test, at the same time, eliminating false positiviness caused by connective diseases, tuberculosis, etc. PMID- 2228037 TI - [Blood deficiency values of polyunsaturated fatty acids of phospholipids, vitamin E and glutathione peroxidase as possible risk factors in the onset and development of acquired immunodeficiency syndrome]. AB - Plasma levels of vitamin E (vit E) and polyunsatured fatty acids of phospholipids (PUFA-PL) as well as erythrocyte glutathione peroxidase (GSH-Px) activity are significantly lower (p less than 0.001) in patients HIV sero-positive (AIDS and ARC cases) both affected and not affected with seborrheic dermatitis and in 32% of HIV sero-negative intravenous drug abusers (IVDA, A subgroup) than in controls. The deficiency of PUFA-PL (mainly C20:3 n-6, C20:4 n-6 and C22:6 n-3) which is associated with a significant increase (p less than 0.001) of saturated palmitic and stearic acids and monounsaturated oleic acid, cannot be correlated to an active lipoperoxidative process. In fact the levels of thiobarbituric acid reactive materials (TBA-RM) are not increased in the plasma of HIV sero-positive patients and A subgroup of IVDA. It is likely that the reduction of PUFA-PL is due to an inhibition of hepatic microsomal desaturase enzymes (delta 6 desaturase, delta 5 desaturase, delta 4 desaturase) which are involved in both n 6 and n-3 pathways. Since IVDA represent, and not only in Italy, a major risk category for HIV infection, we suggest that reduced blood levels of vit E, GSH-Px and particularly PUFA-PL may be added to the list of risk factors favouring the onset and the development of AIDS. PMID- 2228039 TI - [Preliminary experiences with chemotactic activity of CGRP using the skin window test]. AB - The neuropeptide CGRP (Calcitonin Gene-Related Peptide) develops in sensory fibers of the human skin a series of well proven biological effects and seems particularly correlated with the neurogenic inflammation. In the site of intradermic injection of 50 pmol of CGRP, neutrophilic inflammation was documented. For this reason we have studied using the skin window test the chemotactic actions of this neuropeptide in vivo. The apposition of CGRP (12.5 pmol) on the abraded skin modifies neutrophilic egress, increasing that effect in a significant way in comparison with controls. The action on neutrophils of CGRP helps to explain the importance of this neuropeptide in the genesis of the "Neurogenic inflammation". PMID- 2228040 TI - [Histological simulators of Kaposi's sarcoma in the initial phase]. AB - Early Kaposi's sarcoma might be simulated by many different conditions, especially when the vascular component is prominent. the criteria suggested to differentiate early Kaposi's simulators are discussed. We found that these criteria are high in sensibility but low in specificity, therefore, we suggest using these criteria only when they are found in clusters. PMID- 2228041 TI - [Atypical mycobacteriosis caused by Mycobacterium marinum]. AB - Granulomatous lesions located on the hand and on the right forearm have been described in a 67-year-old housewife. They appeared after a small lesion caused by a fish bone, from a piece of frozen fish. Clinical aspect and history together with histological examination are typical of an infection by Mycobacterium marinum. PMID- 2228042 TI - [Reticular erythematous mucinosis (REM). A report of 2 cases]. AB - Cases of reticular erythematous mucinosis have not been frequently observed since Steinglender discovered the disease in 1971. The two patients with a dermatosis having the clinical and histologic characteristics of REM came to our clinic. The biopsies then taken underwent elective colouring for the mucin and was observed under an electron microscope. PMID- 2228043 TI - [Cultured epidermis in the treatment of leg ulcer: "edge effect" and correlation with keratinocyte proliferation index]. AB - Cultured keratinocyte grafting (KG) of chronic leg ulcers produces an impressive stimulation of host epithelization by an effect on the edge of the ulcer, which starts to grow in rapidly ("edge effect"). In 5 patients with chronic leg ulcers treated by KG, we have studied the proliferation index of the epidermis of the edge and of the graft area and that of secondary culture keratinocytes. The aim of the study was to correlate this parameter with the clinical evolution of the treated lesions. We found a significant correlation between the proliferation index of the edge epidermis and the clinical evidence of "edge effect". PMID- 2228044 TI - Revised nomenclature of mouse H-2 genes. PMID- 2228046 TI - The B144-H-2Db interval and the location of a mouse homologue of the human D6S81E locus. PMID- 2228047 TI - Promoter region of HLA-C genes: regulatory elements common to and different from those of HLA-A and HLA-B genes. PMID- 2228045 TI - DNA typing for HLA-DPB1*02 and -DPB1*04 in multiple sclerosis and juvenile rheumatoid arthritis. AB - DP gene typing using in vitro DNA amplification combined with sequence-specific oligonucleotide probes (SSOP) has recently been reported. The amplification step may be specific for the HLA-DPB locus, or it may be specific for one or a group of HLA-DPB alleles, thus increasing the discriminatory power of the system. We report the combined use of group-specific DNA in vitro amplification followed by SSOP in typing for DPB1*02 and DPB1*04 variants. The method was used to type for these variants in 96 randomly selected, healthy Danes, in 37 patients with pauciarticular juvenile rheumatoid arthritis (PJRA), and in 38 patients with multiple sclerosis (MS). Increased frequencies of the cellularly defined HLA-DPw2 in PJRA and of HLA-DPw4 in MS have previously been reported. In the patient groups, the frequencies of the DPB1*02 and DPB1*04 variants did not differ significantly from those expected based on the cellularly defined HLA-DP types of the patients and the frequencies of the DPB1*02 and DPB1*04 variants among healthy Danes. PMID- 2228048 TI - DRB1*LY10--a new DRB1 allele and its haplotypic association. PMID- 2228049 TI - HIV seropositivity among patients with sexually transmitted diseases in Vellore. AB - In a prospective, systematic investigation, 2215 new patients with sexually transmitted diseases (STD) were screened for human immuno deficiency virus (HIV) infection during April 1986 to December 1988. Among them 9 were positive for HIV antibody giving a rate of 4/1000. In addition, 5 patients had been referred to our clinic with a diagnosis of HIV infection and STD. Among these 14, there was one married couple. Of the remaining 5 married individuals, 4 were men; the wives of 3 of them were infected but asymptomatic, and were not included in this report. The rate of conjugal infection was 71 per cent. Most (57%) patients belonged to poor socio-economic background; 78 per cent of patients were young, in the age group 15-25 yr. The presenting STD were syphilis, venereal warts, gonorrhoea, chancroid, genital herpes, non-gonococcal urethritis and candidiasis. It appeared that the course of associated STD had not been altered in these HIV infected individuals. PMID- 2228051 TI - Acute rubella infection in pregnant women in Delhi. AB - Serum samples of 17 pregnant women with suspected rubella who presented at the Department of Microbiology, AIIMS, New Delhi, from March to May 1988 for confirmation of diagnosis were tested for rubella haemagglutination inhibiting (HAI) antibodies and rubella specific IgM antibodies by mu-capture ELISA. Ten of the 17 women were diagnosed to have acute rubella infection as they showed the presence of rubella specific IgM antibodies. Nine of these gave history of fever and rash whereas one woman remained asymptomatic. These observations suggest an increase in the incidence of rubella infection in pregnant women from March to May 1988 in Delhi. PMID- 2228053 TI - Seasonal fluctuations in the occurrence of enteroinvasive Escherichia coli diarrhoea. AB - Enteroinvasive Esch. coli (EIEC) was implicated in 2.1 per cent (57 out of 2661) diarrhoeal patients investigated at Ludhiana (Punjab). The predominant serogroups isolated were 028, 0147, 0124 and 0112. High prevalence of EIEC infection was noticed among infants (50.6%) followed by children up to 10 yr (19.3%). The peak incidence (24.5%) occurred during the hot and dry month of May as compared to 1.7 per cent in February. The disease incidence was positively correlated with mean minimum temperature and mean maximum temperature. All strains gave Sereny's test positive and were mostly susceptible to cephalothin, gentamicin, nalidixic acid, furazolidine and neomycin. PMID- 2228050 TI - Comparison of immunofluorescence & culture for the diagnosis of respiratory syncytial virus infection. AB - In 809 infants and children with acute respiratory infection, HEp-2 cells were used for the isolation of respiratory syncytial virus (RSV) and an indirect immunofluorescence technique (IIF) was used for the detection of RSV antigen in the epithelial cells of nasopharyngeal secretions. While RSV was detected in culture in only 87 subjects, IIF was positive for viral antigen in 158 subjects. In children with bronchiolitis and in those with pneumonia 57 and 19 per cent respectively, had evidence of RSV infection by culture or IIF. The frequency of virus antigen detection by IIF was above 90 per cent irrespective of the duration of symptoms before specimen collection. The frequency of virus isolation in culture was 86 per cent in children with less than 2 days duration of symptoms and 42 to 69 per cent in those with duration of symptoms of 2 days or more. However, this difference was not statistically significant. In conclusion, the IIF test was not only rapid, but also more sensitive for the detection of RSV infection than culture. PMID- 2228054 TI - Phage typing of Vibrio cholerae 01 biotype ElT or strains. AB - Data accumulated over the past 20 yr (1969-88) on the phage typing of V. cholerae 01 biotype ElT or strains received at the Vibrio Phage Reference Laboratory, were retrospectively analysed to ascertain the frequency of occurrence of the different phage types of Basu and Mukerjee typing scheme. The analysis revealed that phage types 2 and 4 were the most common types not only at the time when the Basu and Mukerjee typing scheme (of 1968) was introduced but also at present. The existing phage typing scheme needs to be improved with the addition of more new phages to obtain more type distinction and better discrimination within biotype ElT or strains for epidemiological studies. PMID- 2228055 TI - Effect of drug treatment on the prevalence of intestinal parasites amongst school children in a sub-urban community. AB - The prevalence of intestinal protozoal and helminthic infection was studied over a period of one year amongst 297 school children, aged 5-20 yr in a sub-urban area. The overall prevalence rate of various protozoal infection, 15.82 per cent had only helminthic infection and 14.47 per cent had combined helminthic and protozoal infection. Ascaris lumbricoides infestation was found to be the commonest helminthic infection (61.70%) while giardiasis was the commonest protozoal infection (59.80%). The prevalence rates, one year after effective anti protozoal and antihelminthic treatment was administered, were overall parasitic infection 25.92 per cent; only protozoal infection 17.50 per cent, only helminthic infection 5.72 per cent and combined infection 2.69 per cent. The reinfection rate was found to be 7.40 per cent and the fresh infection rate was found to be 11.4 and 39.8 per cent at the end of six months and one year respectively. PMID- 2228052 TI - Immune response to hepatitis B viral antigens in chronic infection & its relationship with liver necrosis. AB - Markers of hepatitis B virus (HBV) and immune response against them were studied in 18 chronic asymptomatic carriers, 8 patients of the virus induced chronic liver disease (CLD), and 7 patients of chronic alcoholic liver cirrhosis, who were also chronic HBV carriers (CALC). The LMI responses to HBeAg were elevated in HBeAg and/or HBV-DNA positive chronic asymptomatic carriers, (median response 31.5%), along with elevation of serum alanine aminotransferase (sALT) levels (59 150 IU/l). On the other hand the LMI responses to this antigen, in HBeAg and HBV DNA negative chronic carriers were in the normal range (median response 12%) and their sALT levels were also normal (7-50 IU/l). The CLD and CALC patients did not show any relation between their LMI to HBeAg and sALT levels. In contrast no relation between LMI to HBsAg and sALT levels was observed in any group. The LMI responses to HBsAg in CLD patients were elevated (median response 38%) and the responses of chronic asymptomatic carriers and CALC patients were either in the normal range or poor (median responses, 18 and 7% respectively), irrespective of their sALT levels. These results suggest that T cell responses to both the antigens may be involved in liver cell damage. PMID- 2228056 TI - Antibiotic resistance, haemagglutination type & haemolysin production in relation to serogroups of uropathogenic Escherichia coli. AB - A total of 56 urinary isolates of Esch. coli were characterised according to serotype, haemagglutination (HA) type, production of beta haemolysin and antibiotic resistance pattern. Forty five strains were serotyped with prevalence of 057 followed by other serotypes. Eleven different Esch. coli serotypes were found to have mannose resistant haemagglutinating property (MRHA) and just five strains showed haemolysin production (Hly+). Multidrug resistance was common with preponderance of ampicillin, co-trimoxazole and tetracycline resistance. No correlation between serogroup, HA type, haemolysin production and antibiotic resistance was found. PMID- 2228057 TI - Enzyme linked immunosorbent assay for immunoglobulins G to Mycoplasma hominis. AB - Sera (187) from women patients attending the STD, Obstetrics and Gynaecology, and Family Planning Clinics were screened for the presence of the IgG class of immunoglobulins against M. hominis, using the ELISA technique. Sonicates of locally isolated M. hominis serotype (CS1) and standard PG 21 strain were used as antigens. The test was standardized using penicillinase as an enzyme. The ELISA showed 90.48 per cent sensitivity and 84.8 per cent specificity, and was also rapid (as compared to culture) and reproducible. PMID- 2228058 TI - Double blind clinical trial on centperazine & DEC in bancroftian filariasis. AB - Centperazine, an analogue of DEC, was subjected to a double blind controlled trial, to evaluate its efficacy as a newer antifilarial agent. Centperazine (300 mg/day) along with equivalent quantities of DEC and placebo were administered to different types of filariasis patients. DEC was found to be significantly effective in reducing peripheral microfilaraemia, in different weeks and months of follow-up, except at the end of 6th month, as compared to Centperazine. There was no significant difference between the placebo and Centperazine treated patients, in this respect, revealing that the drugs had no efficacy in eliminating peripheral microfilaraemia. Recurrence of acute attack within 6 months was nearly equal with both Centperazine and DEC, being 28.2 and 24 per cent respectively, whereas in the placebo group the recurrence rate was 48.9 per cent. Centperazine treated patients showed significantly less side effects (8.9%), as compared to DEC treated patients (34%). Giddiness, nausea and vomiting were the common adverse effects observed. PMID- 2228060 TI - A mathematical analysis of various factors involved in transmission of bancroftian filariasis in Pondicherry. AB - The variation of clumping factor in microfilaraemia among different age groups was observed in Pondicherry for 1981 and 1986. The clumping factor was minimum in the age group 0-5 yr and it was maximum in 16-20 yr group in 1981 and 21-25 yr in 1986. The variation in clumping factor resembled the changes in microfilaria (mf) rate. Multiple linear regression analysis showed that the multiple correlation between mf rate and the other parameters i.e., median microfilarial density (MFD50), clumping factor in human population, and, infection rate and infectivity rate in vector population was highly significant. The relationship between filariometric indices in human host and vector population may provide the basis on which a mathematical model on transmission of filariasis could be developed. PMID- 2228059 TI - Choice & integration of different approaches to case detection with special reference to brugian filariasis in south India. AB - Treatment following rapid case detection in population, particularly the target age classes, which record high prevalence, is necessary for effective control of lymphatic filariasis. Conventional door-to-door surveys resulted in delay in detection of parasite carriers and patients with clinical filariasis, particularly in rural areas. An integration with other approaches like school surveys, health camps, filariasis clinics and microfilaria detection camps (MDC) was found effective in covering a much larger population in brugian filariasis case detection in an endemic area in south India. The MDCs organized through Integrated Child Development Scheme (ICDS MDC) yielded a good coverage of pre school children. School surveys were ideal in covering children en masse. Community MDCs and health camps arranged with active community participation were useful in covering adolescents and young adults in large numbers. The filariasis clinic was effective in screening older adults above 30 yr. The relative efficiency of these approaches in terms of time and manpower utilization has been discussed. PMID- 2228061 TI - Estimation of fecundic life span of Wuchereria bancrofti from longitudinal study of human infection in an endemic area of Pondicherry (south India). AB - The fecundic life span of adult female W. bancrofti was estimated by longitudinal study of microfilaraemia in a cohort of population (7,525) in Pondicherry. The estimation was based on a deterministic model, using the rate of loss in infection. The life span of the parasite was 10.2 yr without chemotherapy, while it was reduced to 5.3 yr following diethyl-carbamazine therapy. The analysis of mean microfilarial counts in microfilaraemic persons without chemotherapy indicates that the rate of production of microfilaria by the adult female is stable at least for a period of five years. PMID- 2228063 TI - Plasma levels of estradiol & progesterone at different gestational ages in Indian women. AB - Plasma levels of estradiol and progesterone were determined at different gestational ages in Indian pregnant women from the low socio-economic group. The levels of estradiol and progesterone progressively increased with gestation and reached maximum values (14.35 +/- 1.092 and 145.9 +/- 7.69 ng/ml, respectively) by term. Though the estradiol values were comparable to those reported in literature, the term values of progesterone were found to be lower (145.9 +/- 7.69 ng/ml) than those reported from Western countries (160 +/- 7.5 ng/ml) at 34 38 wk of gestation. These low progesterone values may have physiological implication in placental function. PMID- 2228062 TI - An improved method of mass culturing of Romanomermis iyengari, a mermithid nematode parasite of mosquito larvae. AB - An attempt was made to develop an alternative method of mass culturing for R. iyengari instead of the usual sand culture method. Fifty pairs each of post parasitic juveniles were seeded in moist sandbed and beakers containing tap water and distilled water and examined for exsheathing, egg-laying and egg-hatching. All post-parasitic juveniles in the moist sandbed had moulted by 7th day whereas in tap water and distilled water it lasted up to 11th day. Maximum numbers of eggs were observed on day 14 in sandbed (15/ml), day 16 in tap water (24/ml) and day 29 in distilled water (28/ml). The preparasites obtained from moist sandbed, tap water and distilled water did not exhibit any difference in their infectivity to mosquito larvae. The eggs of the nematode obtained from a culture in distilled water maintained at 30 +/- 2 degrees C for 60 days, when treated with CO2 (18 to 556 ppm) showed enhanced rate of egg hatching (73-98% compared with 11.5% in the untreated ones). CO2 treatment did not affect the infectivity of the preparasites that hatched from the CO2-treated eggs. PMID- 2228064 TI - Perinatal outcome in relation to maternal glycaemic control in diabetic mothers. AB - The relationship between glycaemic control and perinatal outcome was assessed in 60 pregnant diabetic women, divided into three groups on the basis of the mean plasma glucose level. Group I, had mean plasma glucose less than 120 mg/dl (32 patients); group II, mean plasma glucose 121-140 mg/dl (13 patients); and group III, mean plasma glucose exceeding 140 mg/dl (15 patients). The degree of maternal glycaemic control appeared to affect the perinatal outcome. Neonatal morbidity was minimum in group I (31.25%) followed by group II infants (46.15%) and maximum in group III infants (66.6%). Maintenance of maternal plasma glucose level at or below 120 mg/dl was thus associated with minimum neonatal morbidity. PMID- 2228065 TI - Prevalence & clinical associations of anticardiolipin antibodies in patients with systemic lupus erythematosus in India. AB - Anticardiolipin antibody (aCL) screening using an ELISA technique, in 76 patients of Indian origin with systemic lupus erythematosus (SLE), showed aCL in 27.63 per cent of patients. This prevalence was much lower than that reported in the Western population. The presence of aCL showed positive correlations with recurrent abortions and organic neurological lesions seen in SLE. PMID- 2228066 TI - Non-organ specific & organ specific antibodies in rheumatoid arthritis. AB - Fifty patients of rheumatoid arthritis clinically diagnosed (by ARA criteria) were studied for both non-organ specific [rheumatoid factor (RF), anti-nuclear antibodies (ANA), extractable nuclear antibody (ENA), granulocyte specific anti nuclear antibody (GS-ANA), anti-smooth muscle antibody (SMA) and anti mitochondrial antibody (AMA)] and organ specific, [anti-adrenal (AAA), anti-islet cell (ICA), antithyroid antibody (ATA) and anti-parietal cell (PCA)] auto antibodies. RF was positive in 80 per cent of patients. ANA was positive in 44 per cent of patients, ENA in 62 per cent, SMA in 20 per cent, AMA in 18 per cent and GS-ANA in 68 per cent. Of the organ specific antibodies, PCA was demonstrable in 28 per cent of the patients and none of the other antibodies were present. Circumstantial evidence indicates that ANA and GS-ANA are not synonymous but independent, cross-reacting entities and the presence of both increase the sensitivity (94%) of diagnosis of RA. PMID- 2228067 TI - Prevalence, awareness & treatment status of hypertension in urban population of Delhi. AB - A community based survey for the prevalence of hypertension was carried out on a random urban sample of 13,723 adults in the age group 25-64 yr from the Union Territory of Delhi (India). Hypertension was defined as systolic pressure greater than 160 mm Hg and/or a diastolic pressure greater than 90 mm Hg or a history of current antihypertensive medication. The overall prevalence rate/1000 adults was 127.5 (116.6 in males and 136.8 in females). Mild hypertension (diastolic pressure between 91-104 mm Hg) predominated in the whole group, the proportion decreasing with increasing age in both sexes. Fifty per cent of the hypertensives were aware of their problem, the awareness being slightly higher in females (51.8% versus 46.5%). Approximately 30 per cent of the hypertensives were on medication for high blood pressure. The status control of blood pressure was low in the population, being only 9 per cent, with little difference between the two sexes. The study emphasises the enormity of the problem of hypertension in an urban population in India and poor control of blood pressure achieved in the community. PMID- 2228068 TI - Alterations in immunoglobulin & complement levels in chronic obstructive pulmonary disease. AB - Thirty patients of chronic obstructive pulmonary disease (COPD; all smokers) and an equal number of controls (15 smokers) were studied. The COPD patients were further divided into group A (predominantly emphysema) and group B (predominantly bronchitis) of 15 patients each. Serum and sputum IgG, IgA and IgM and serum C3 and C4 were estimated. IgG, IgA, IgM and C3 and C4 were similar in smoker and non smoker controls. Mean (+/- SD) serum IgG (IU/ml) was significantly higher in COPD patients (207.78 +/- 62.73) than in control (177.25 +/- 43.5; P less than 0.05), serum IgA (IU/ml) was also significantly higher in COPD (205.04 +/- 46.56) than in control (108.21 +/- 33.3; P less than 0.01). IgM was similar in the 2 groups. Sputum IgA (IU/ml) was higher in COPD (4.68 +/- 3.51) than in control (2.25 +/- 1.03; P less than 0.05). IgG and IgM were similar in the 2 groups. Both serum C3 (IU) and C4 (IU) were lower in COPD patients (C3 = 95.9 +/- 33.11, C4 = 113.6 +/- 62.4) than in control (C3 = 167.3 +/- 25.42, C4 = 205 +/- 76.5; P less than 0.05). Serum IgA in type B COPD (212.25 +/- 50.06) was higher than in type A (197.52 +/- 43.3; P less than 0.05) IgG and IgM were similar in these 2 groups. In COPD patients, immunoglobulins were either normal or higher indicating that deficiency of immunoglobulin is not a predisposing factor in development of COPD. Similar immunoglobulin values in smoker and nonsmoker controls indicated that smoking was not the cause of rise of immunoglobulins in COPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228071 TI - Circadian variation of serum urea concentration in north Indian subjects. AB - Circadian rhythm of serum urea concentration was studied in 25 clinically healthy, diurnally active, nocturnally resting young male Indians. The mean urea concentration was observed to be 22.32 mg/dl at 0800 h which increased gradually reaching maximum at 0000 h with a mean of 31.00 mg/dl. A marked circadian variation in serum urea was recorded with a statistically significant amplitude and acrophase at 2232 h (Cosinor analysis). The observation that serum urea concentration oscillates physiologically in the peripheral blood according to a circadian rhythm may prove to be of importance in the clinical interpretation of values at different times along the 24 h light-dark period. PMID- 2228069 TI - Simplified technique for recording human cortical & spinal evoked muscle potentials. AB - Muscle responses evoked on transcranial stimulation of the motor cortex (corticomotor) and motor roots (spinal) were studied in 20 healthy volunteers using a simplification of Rossini's technique and conventional EMG equipment. Cortical motor responses were consistently obtained from the contralateral upper limb with tolerable stimuli. Lower limb motor responses were inconsistent and sometimes required uncomfortably high stimulus strengths. In the upper limbs, peripheral conduction time (PCT) was estimated by the latency of the response to spinal stimulation. A comparable measure of PCT was obtained for the abductor pollicis brevis (APB) from the F-responses. The difference between the latency of the corticomotor response and the PCT was considered to represent central motor conduction time (CMCT). Corticomotor latencies were: APB 18.51 +/- 1.1 msec, biceps 9.77 +/- 0.46 msec and tibialis anterior 26.5 +/- 2.9 msec. CMCT from cortex to C8/T1 segments (APB) was 4.68 +/- 0.6 msec and between cortex and C5/C6 (biceps) 4.24 +/- 0.42 msec. PMID- 2228070 TI - Auditory brainstem evoked responses in healthy north Indians. AB - Auditory brainstem evoked potential responses (ABR) were recorded from CZ-A1 and A2 scalp regions in 132 healthy normal subjects in four age groups (in yr; less than 15, 16-25, 26-45 and greater than 46). The normative data for absolute, interpeak latencies and amplitude of waves V and I in each group are being reported. A mean value of 2.09, 1.85 and 3.97 msec for IPLs I-III, III-V and I-V respectively is worked out representing a normal baseline, irrespective of age. As significant sex related differences are seen in IPLs, two separate values for male and females are given along with 99 per cent tolerance limit. The values of IPLs for males are 2.13 (2.58 TL) for I-III, 1.88 (2.30 TL) for III-V, 4.03 (4.48 TL) for I-V and for females 2.05 (2.44 TL) for I-III, 1.80 (2.25 TL) for III-V, 3.89 (4.42 TL) for I-V in msec. These values in Indian subjects are comparable to those reported in the West. PMID- 2228072 TI - Coitus induced changes in oviductal motility & effect of progesterone. AB - Motility of different oviductal segments of conscious rabbits was recorded through permanently implanted sensors using the technique of impedance plethysmography. The implants were around the oviductal wall and therefore did not obstruct its lumen. Pre-ovulatory ampullary motility was always less than the isthmic motility. Coitus induced ovulation produced a characteristic oviductal motility pattern consisting of (i) initial relaxation of both isthmus and ampulla (4-12 h) followed by (ii) increased isthmic motility in the face of a continually relaxed ampulla (36-48 h), and finally phase (iii) leading to restitution of both ampullary and isthmic motility to the base-line at 72-96 h. Estimation of ova positions indicated the presence of fertilized eggs in the ampulla and ampullo isthmic junction at 48 h and the ova could come to the end of the isthmic segment only at 72 h or after. Increased isthmic motility thus served to counter the transportation of ova and their retention in the ampulla. Rabbits in which oviducts were not taken out for ova positioning achieved normal pregnancy. Administration of progesterone (im, 2.5 mg) produced complete relaxation of both isthmus and ampulla, did not produce increased isthmic contractility on coitus, accelerated the ovum transport rate and inhibited pregnancy, again emphasising the ova retentive role of oviductal motility. PMID- 2228073 TI - Immune response to syngeneic spermatozoa & its effect on target organs in mice. AB - Two groups of adult Swiss mice were immunised with washed syngeneic spermatozoa without any adjuvant for a period of two months or four months respectively. The presence of antibodies to spermatozoa was measured by micro sperm-agglutination and micro sperm-immobilization tests. The development of cell mediated immune response (CMIR) was measured by leucocyte migration inhibition test (LMIT) using spermatozoal antigens solubilized by 3M KCl, Nonidet P-40 or by subjecting the cells to ultrasonication. SDS-PAGE analysis of these proteins indicated that extraction of spermatozoa with 3 M KCl was a better method for solubilization of antigens present on sperm membrane. Almost all immunized mice had varying titers of sperm agglutinating antibodies. Nearly 40-50 per cent of the mice had a titre of 1:128 in both groups whereas only 33 per cent had sperm immobilizing antibodies. CMIR, as assessed by LMIT, was detected in immunized mice. However, this had not resulted in the infiltration of immune cells into the target organs perhaps due to the lower magnitude of immune response. PMID- 2228074 TI - Hepatoprotective activity of andrographolide from Andrographis paniculata against carbontetrachloride. AB - Andrographolide, a diterpenoid lactone, was isolated (yield 0.78% w/w) from A. paniculata (whole plant). Its LD50 in male mice was 11.46 g/kg, ip. Antihepatotoxic activity of andrographolide (100 mg/kg, ip) was compared with 861.33 mg/kg, ip, of the methanolic extract (equivalent to 100 mg/kg of andrographolide) and 761.33 mg/kg ip, of the andrographolide-free methanolic extract (equivalent to 861.33 mg/kg of the methanolic extract) of the plant, using CCl4-intoxicated rats. Biochemical parameters like serum transaminases--GOT and GPT, serum alkaline phosphatase, serum bilirubin and hepatic triglycerides were estimated to assess the liver function. Overall inhibition of CCl4-induced increase in the five biochemical parameters was found to be 48.6 per cent (andrographolide), 32.0 per cent (methanolic extract) and 15.0 per cent (andrographolide-free methanolic extract). These biochemical observations were supplemented by histopathological examination of the liver slices. Further, andrographolide (100 mg/kg, ip) was found to normalize completely the CCl4 induced increase in the pentobarbitone induced sleep time of mice. The results suggest that andrographolide is the major active antihepatotoxic principle present in A. paniculata. PMID- 2228075 TI - Hepatoprotective activity of andrographolide against galactosamine & paracetamol intoxication in rats. AB - Hepatoprotective effect of andrographolide (the major active diterpenoid lactone of the plant Andrographis paniculata) was studied on acute hepatitis induced in rats by single dose of galactosamine (800 mg/kg, ip)/paracetamol (3g/kg, po). Hepatoprotective activity was monitored by estimating the serum transaminases (GOT and GPT), alkaline phosphatase and bilirubin in serum, hepatic triglycerides, and by histopathological changes in the livers of experimental rats. Pre-treatment and/or post-treatment of rats at different time intervals with different doses of andrographolide in the two experimental models of hepatotoxicity showed that treatment of rats with 400 mg/kg, ip or 800 mg/kg, po, 48, 24 and 2 h before galactosamine administration or with 200 mg/kg, ip, 1, 4 and 7 h after paracetamol challenge leads to complete normalisation of toxin induced increase in the levels of all the five biochemical parameters, and significantly ameliorates toxin-induced histopathological changes in the livers of experimental rats. The results confirmed the in vivo hepatoprotective effect of andrographolide against galactosamine or paracetamol-induced hepatotoxicity in rats. Since the protective effect of andrographolide was observed in two types of intoxication, which are very different in their primary mechanism of inducing hepatotoxicity, it is suggested that protective mechanisms of andrographolide which are not specific to galactosamine or paracetamol toxicity may be responsible for the hepatoprotective activity of the compound. PMID- 2228077 TI - Efficacy of indomethacin suppository in primary dysmenorrhoea. AB - The efficacy of indomethacin suppositories (100 mg 1-3 times a day) in the treatment of primary dysmenorrhoea was investigated in a double-blind, crossover study involving 40 patients, in comparison to placebo. The patients were treated for four menstrual periods-two periods with placebo and two periods with indomethacin suppositories. A dysmenorrhoeic score based on subjective estimations of nine symptoms was used, the symptoms including pelvic pain, backache, headache, dizziness, nausea, vomiting, diarrhoea, nervousness and incapacitation. As compared to placebo, indomethacin suppositories led to a insignificant decrease in the frequency and severity of the associated symptoms, as evaluated by subjective rating (P less than 0.05). Indomethacin suppositories were well tolerated and there was no drop-out. No side effects were reported except for a mild burning sensation in the rectal region experienced by 3 patients on indomethacin suppositories. PMID- 2228076 TI - Changes in the sensitivities of dopamine receptors to chronic treatment with imipramine & haloperidol in rats. AB - Apomorphine induced locomotor activity was studied in Wistar rats treated with imipramine and haloperidol with the help of automated measuring devices. The control rats showed a biphasic response of hypomotility and sedation to low dose apomorphine, and hypermotility to high dose apomorphine. In chronic imipramine treated rats, the hypomotility and sedative response to low dose apomorphine challenge was significantly attenuated (P less than 0.05), as compared to saline treated controls. A similar response was observed in the chronically haloperidol treated rats (P less than 0.01). However, there were no significant differences in motility responses to high dose apomorphine challenge between the control and experimental groups. These results suggest that presynaptic dopamine auto receptors may not be involved in mediating the loss of response to low dose apomorphine by chronic imipramine treatment. Imipramine being predominantly a monoamine uptake inhibitor and haloperidol a potent postsynaptic D-2 blocker, some indirect mechanisms may be involved in the loss of response to low dose apomorphine challenge. PMID- 2228078 TI - Children and environment: A UNICEF Strategy for Sustainable Development. PMID- 2228079 TI - The painful hip. PMID- 2228081 TI - Care of the uncircumcised penis. PMID- 2228080 TI - Circumcision in children. PMID- 2228082 TI - Pediatric neurology. PMID- 2228083 TI - Approach to epilepsy in children. PMID- 2228084 TI - Subependymal-intraventricular hemorrhage in the newborn. PMID- 2228085 TI - Acute hemiplegia in infancy. PMID- 2228086 TI - Muscular dystrophies. PMID- 2228087 TI - Headaches in childhood. AB - The diagnosis and management of headache in children is a challenge to the clinician, covering as it does a wide range of diagnostic possibilities and enlisting a range of skills from neurosurgery and infectious disease to the psychological. The task is best undertaken, as in so many medical problems, by taking careful history and physical examination, including the past history, family history, and life circumstance of the child. After this is done, only in a minority of cases will it be necessary to request a specific special test, such as a CT scan, lumbar puncture or EEG. In those cases where doubt remains after initial careful evaluation or even after special studies have not resolved the question, careful follow up of the child over time, with re-examination as necessary, will allow definitive diagnosis and prevent the physician from missing obscure or in apparent disease. PMID- 2228088 TI - Attention deficits and hyperactivity. AB - The precise nature of the relationship among attention deficit, hyperkinesis, and specific learning disabilities remains a mystery. They are encountered in one another's company with far greater than chance frequency. It is clear, on the one hand, that attention deficit and learning disability aggravate one another; that is, that what is difficult to learn is difficult to attend to, and vice versa. Furthermore, in children at least, attending ability and activity level have a reciprocal relationship; that is, improvement of attention tends to reduce activity level, and vice versa. On the other hand, each of these disorders is seen in isolation with sufficient frequency to assure us that none of the three is simply a by-product of one or both of the other two. It is unlikely that a single etiology will be identified to account for a significant number of cases of hyperactivity or attention deficit, and thus unlikely that a "cure" or even a mode of prevention will be found. A change in the attitude of the culture toward formal education would reduce the morbidity of the syndrome, but this is also unlikely in the foreseeable future. What further research does promise to yield are medications that improve attention span with fewer side effects, and perhaps more important, more workable technologies for changing behaviour and engineering environments to encourage academic productivity in the face of this important aptitude deficit. PMID- 2228090 TI - Experiences with milk banking in Bombay. PMID- 2228091 TI - G6PD deficiency in neonates: a prospective study. AB - One thousand consecutively born babies were screened for G6PD deficiency and observed for seven days for development of jaundice. Frequency of the deficiency was 3.9%, being 5% in males and 2.8% in females. Religion did not have any bearing on the frequency. Parental screening in cases of babies deficient in G6PD enzyme revealed deficiency of the enzyme in majority of the mothers. Hyperbilirubinemia developed in 48.7% of babies having G6PD deficiency : It is recommended that any neonate presenting with jaundice must be screened for G6PD deficiency not only to define the etiology of hyperbilirubinemia but also to prevent future hemolytic episodes. PMID- 2228089 TI - Human milk banking: current concepts. PMID- 2228092 TI - Standard curves for mid arm circumference and mid-arm/head circumference ratio in newborns. AB - One Thousand singleton neonates, between 28 and 44 weeks of estimated gestational age (EGA) were measured within 48 hours of their birth for upper mid-arm circumference (MAC), head circumference (HC) and birth weight (BW). Regression analysis was used to draw standard curves for MAC versus EGA and mid-arm circumference/head circumference ratio (MAC/HC) versus EGA. Correlation coefficients were 0.961 for MAC versus EGA and 0.889 for MAC/HC versus EGA (p less than 0.001). MAC, MAC/HC and HC were also highly correlated with birth weight (p less than 0.001). These standard curves make available a discriminating method for evaluation of intra-uterine growth and a non-invasive technique for following somatic protein status in growing preterm infants. PMID- 2228093 TI - Maternal knowledge regarding breast feeding and weaning practices. AB - The study assessed the knowledge of mothers of the high income group of urban Baroda, related to breast feeding and weaning. Forty mothers with children aged 4 to 18 months were studied. Knowledge and practices regarding breast feeding and weaning were assessed using pretested questionnaires. Results indicated that only half the mothers breast fed their babies on the first day. Breast feeding was stopped when the child was 3-6 months; top feeding and solid supplements were initiated at 4-6 months. Mainly commercial baby foods were used for weaning. Most mothers avoided 'dals' for the child because these were believed to be difficult to digest and produced gas in the child's stomach. Fifty percent of the mothers were not in favour of feeding the sick child with small frequent meals. PMID- 2228094 TI - Knowledge and attitude towards breast feeding among adolescent girls. AB - Majority of the urban adolescent girl students (n = 76) from middle socioeconomic group correctly reported that breast milk is the best food for infants (95%), and it has protective antibodies (98%). However, most of them (92%) had incorrect knowledge about the role of diet in breast milk secretion and continuation of breastfeeding while mother is suffering from tuberculosis (92%), malaria (84%). PMID- 2228095 TI - Sister chromatid exchanges in congenital cataracts. AB - A total of 25 patients with bilateral congenital cataracts, from three aetiological groups i.e. rubella (6 patients) hereditary (6 patients) and undetected aetiology (13 patients) were studied for sister chromatid exchanges (SCE). SCEs were markedly raised in the rubella groups as compared with age sex matched controls. The other two groups also showed raised SCE, more so in hereditary group. PMID- 2228096 TI - Dermatoglyphic profile in congenital cataracts. AB - Forty-five children with congenital cataract cases were studied for patterns and compared with age sex matched controls. The patients showed marked differences in different dermatoglyphic traits. The intra uterine aetiological groups i.e. rubella, hereditary and undetected aetiology, showed variations in mainline terminations. Rubella group showed increased angle atd. PMID- 2228097 TI - Pediatric emergency news letter no. 11. PMID- 2228099 TI - Vein of Galen aneurysm. PMID- 2228100 TI - Glycosylated hemoglobin level: an indicator of fetal birth weight and perinatal outcome. PMID- 2228098 TI - Congenital leukemia. PMID- 2228101 TI - Cryptosporidiosis in children with diarrhea. PMID- 2228102 TI - Renal amyloidosis. PMID- 2228105 TI - Complex mixtures and cancer risk. PMID- 2228104 TI - Complex mixtures and cancer risk. PMID- 2228103 TI - Cancer: causes, occurrence and control. PMID- 2228106 TI - Use of bacterial assay system for monitoring genotoxic complex mixtures in the occupational setting. AB - Workplace environmental genotoxicity assessments, which may be carried out either by laboratory analysis or using an in-situ assay system, are potentially useful for health hazard evaluations, for industrial hygiene and biological (genetic) monitoring. Whenever possible, genotoxicity assays should be performed in conjunction with industrial hygiene studies to assess the biological activity of workplace contaminants. Efforts should continue to be made to establish a simple and reliable in-situ assay system for the detection and monitoring of genotoxic complex mixtures in the occupational setting. PMID- 2228108 TI - Approaches to detecting individual exposure to carcinogens. AB - Specific and sensitive methods are now available to detect DNA and protein adducts induced by a variety of carcinogens. These measurements of individual exposures are now starting to be used in cancer epidemiological studies. In this paper the requirements and the problems in implementation of the studies are discussed, as well as aspects of interpretation of the results in relation to assessments of past exposure and biological relevance to the disease process. PMID- 2228107 TI - Chemical mixtures and interactive carcinogenesis: in vitro studies. AB - Interactive effects in carcinogenesis have been described for a certain number of combinations of agents. They are described in terms of inhibition or enhancement of carcinogenesis, and the latter can involve either synergistic, cocarcinogenic or promotional action. Such effects constitute an important consideration to be borne in mind in assessment of the risks due to complex exposures. PMID- 2228109 TI - Approaches used by the US National Toxicology Program in assessing the toxicity of chemical mixtures. AB - The US National Toxicology Program has made a definite commitment towards improving the understanding and predictability of the toxicity of chemical mixtures. The commitment has consisted of a thorough review by the National Research Council of the state of the art of complex mixture testing and strategy for in vivo tests as well as a series of laboratory studies to better characterize the toxicity of selected chemical mixtures and research programmes to improve our ability to predict the toxicological properties of other mixtures. PMID- 2228110 TI - Analytical tools and biomonitoring for carcinogens in complex mixtures. AB - Two approaches are described for the analysis and biomonitoring of complex mixtures: (a) activity-guided fractionation of pyrolysed opium followed by spectroscopic determination of molecular structure and (b) trapping of possibly genotoxic metabolites by a series of microencapsulated, recoverable, synthetic macromolecular targets within the milieu of the gastrointestinal tract. Opium pyrolysis was shown to produce (principally from morphine) a series of hydroxyphenanthrenes of novel structure having activity not only in the S. typhimurium used as a guide, but also in a variety of in vitro and in vivo test systems. Many analytical tools were used together for separation, structure determination and activity monitoring, and their relative merits and overall strategy are discussed. The microcapsules have been shown to trap carcinogens, nitrosating agents, cross-linking agents and aldehydes. Their trapping of a model carcinogen in vivo is modulated by components of human diets. Development of these microcapsules for detecting endogenous carcinogens and their sources is discussed with reference to the type of target and analytical tools that may be appropriate. PMID- 2228111 TI - Cytogenetic markers in detecting the effects of exposure to complex mixtures of chemicals. AB - A significant proportion of the mutations responsible for both inherited and acquired human disease are a consequence of chromosome structural changes and of losses or gains of whole chromosomes. Some of these changes are readily detectable by the cytogeneticist and their frequencies are increased following exposure of individuals to mutagens. Techniques to visualize human sperm chromosomes and to detect micronuclei in spermatids now allow the cytogeneticist to detect induced chromosomal mutations in human germ cells. Rapid advances in our understanding of the molecular organization of the human genome, in the application of recombinant DNA probes and in situ hybridization with isotopic and non-isotopic probes, now enable chromosome organelles and specific chromosomal regions to be uniquely identified. These approaches are being applied to analyse chromosomal changes in somatic cells and, coupled with the development of machines to rapidly analyse chromosomes and nuclei, provide a powerful means to utilize cytogenetic markers to detect the effects of exposure of people to complex mixtures of chemical mutagens. PMID- 2228112 TI - The effect of background variables on human peripheral lymphocyte micronuclei. AB - Application of biological methods for assessment of occupational and environmental exposure to single agents or complex mixtures is optimized by determination of the possible influence of background factors on the biological endpoint of interest. Analysis of micronuclei in peripheral blood lymphocytes using the cytokinesis-block method was performed on healthy volunteers up to three times for each individual at intervals of approximately four months. Questionnaires were administered to ascertain recent health history and lifestyle factors such as smoking and drinking habits. Results to date indicate that age (r = 0.45, p = 0.001) and estimated number of diagnostic X-rays during the past year (r = 0.35, p = 0.01) contribute significantly to increased frequency of micronuclei. Information on the potential influence of background factors is critical for appropriate statistical analysis of data from occupational and population monitoring studies that utilize the cytokinesis block lymphocyte micronucleus assay to assess exposure to genotoxic agents. PMID- 2228113 TI - Quantitation of chromatin patterns by image analysis as a predictive tool in chemopreventive trials with vitamin A. AB - Nuclear textures of oral mucosal cells were quantitated by image analysis, and their suitability as markers in a chemopreventive trial explored. Subjects were chewers of tobacco-containing betel quids with well established oral leukoplakias. Treatment consisted of a weekly oral administration of vitamin A (200,000 IU/week) for six months. Leukoplakias regressed in 57.1% of the 21 trial participants. The original leukoplakias did not redevelop within four months after termination of treatment. For image analysis, biopsies were taken from leukoplakias of five chewers before administration of vitamin A, at the end of the administration, and four months after termination of treatment. Sections of paraffin-embedded biopsies were stained with the Feulgen reaction and submitted to quantitative image analysis of two parameters: variance of intensity and entropy. Both these parameters were significantly reduced in all five trial participants as a result of the six-month vitamin A treatment. During the post treatment period, nuclei with condensed chromatin, as measured by the variance of intensity, reappeared in the mucosa of four of the five chewers examined, although no leukoplakias were detectable on visual examination of the oral cavity. The results indicate that the quantitation of nuclear textures in a small subpopulation of a chemopreventive trial could conceivably be a simple marker with a predictive value. PMID- 2228116 TI - Polycyclic aromatic hydrocarbon-DNA adducts in coke-oven workers. AB - Different approaches for measuring occupational exposure to polycyclic aromatic hydrocarbons (PAHs) are presented, (i) determination of PAHs in the workplace by personal sampling, (ii) determination of urinary PAHs and PAH metabolites, and (iii) measurements of aromatic DNA adducts in white blood cells by ultra sensitive enzyme radioimmunoassay (USERIA) and 32P-postlabelling. Large amounts of PAHs, including benzo[a]pyrene (BP), are released from the coke ovens. Mean PAH exposure levels were reduced by 60% when the workers used masks during work. However, low PAH concentrations were found in the urine of the exposed workers. Approximately 40% of the coke-oven workers had detectable levels of benzo[a]pyrene diol epoxide (BPDE)-DNA adducts in the white blood cells measured by USERIA and 90% had levels of aromatic adducts detectable by the 32P postlabelling assay. In this study there was a correlation between DNA adduct levels and estimated exposure. PMID- 2228115 TI - DNA adducts in humans related to occupational and environmental exposure to aromatic compounds. AB - White blood cell DNA adducts were measured in coke workers, local controls and countryside controls using the 32P-postlabelling technique and immunoassay. The methods detected aromatic adducts, including those formed by polycyclic aromatic hydrocarbons. Coke workers are heavily exposed to aromatic compounds, which are also emitted in large amounts into the environment. The two techniques detected a large difference in adduct levels between the coke workers and the countryside controls. The adduct levels in the local controls were substantially higher than those in the countryside controls. As occupational exposure did not account for such a difference, the data suggest that the source of aromatic adducts in local controls is environmental pollution. PMID- 2228117 TI - Biologically based models for risk assessment. AB - The modelling problems associated with the estimation of risks from long-term chemical exposures at low dose levels represent a statistical and mathematical challenge with special relevance to environmental research. Determining an adequate model for estimating the relationship between dose and response is critical to reducing potential bias in the risk estimation process. This paper discusses the various assumptions and models used in carcinogenic risk assessment. The emphasis is on our ability to accurately determine the magnitude of the carcinogenic risk, the shape of the dose-response relationship and the overall variability of the risk estimates. PMID- 2228114 TI - Macromolecular adducts and related biomarkers in biomonitoring and epidemiology of complex exposures. AB - In order to evaluate the potential of biological markers in epidemiology and risk assessment of complex exposures, we review recent studies of macromolecular adducts and oncogene activation in human populations. Results are discussed in terms of the strengths and weaknesses of various study designs in order to identify the most promising approaches for future research. PMID- 2228119 TI - Biological monitoring of human exposure to coal tar. Urinary mutagenicity assays and analytical determination of polycyclic aromatic hydrocarbon metabolites in urine. AB - The mutagenicity of urine extracts from anode plant workers exposed to coal tar pitch volatiles and non-smoking psoriatic patients treated with coal tar applications and UV light (Goeckermann regimen), was determined by the plate incorporation assay and the fluctuation test employing Salmonella typhimurium strain TA98 in the presence of rat liver post-mitochondrial fractions and deconjugating enzymes. The levels of total polycyclic aromatic hydrocarbons (PAHs) and of a marker metabolite of pyrene (1-hydroxypyrene) were determined in the urine of the same subjects. Both the occupational and in particular the therapeutic exposure to coal tar resulted in clear increases in urinary levels of PAH metabolites as compared to unexposed subjects. The level of 1-hydroxypyrene in the urine samples was comparable to or even greater than the corresponding level of total PAHs, indicating a poor recovery of PAH metabolites for this method. Following treatment with coal tar, most of the psoriatic patients excreted clearly increased levels of mutagens in their urine, while non-smoking anode plant workers showed no increase in urinary mutagenicity. The minimum levels of PAH metabolites corresponding to a significant increase in urinary mutagenicity varied from sample to sample, presumably depending on interfering factors present in different amounts in the extracts. Nonetheless the urine samples which were clearly mutagenic presented elevated levels of PAH metabolites, suggesting that the mutagenicity assays lack sufficient sensitivity to allow their application in the biological monitoring of most occupational exposures to coal tar. PMID- 2228120 TI - DNA adduct formation in human and mouse skin by mixtures of polycyclic aromatic hydrocarbons. AB - 32P-Postlabelling analysis has been used to detect the formation in vivo of DNA adducts by components of complex mixtures of polycyclic aromatic hydrocarbons (PAHs) in coal-tar, creosote, bitumen, juniper tar, used engine oils and fuel exhaust condensates. The presence of DNA adducts derived from these agents has been investigated in mouse skin, in human skin explants maintained in short-term organ culture and in human skin in vivo, and the formation of many different PAH DNA adducts was observed. Similar levels and patterns of adducts were found in DNA from human skin to those in mouse skin, which is known to be susceptible to the carcinogenic activity of PAH mixtures, thus demonstrating the potential hazard to man of epidermal contact with these materials. PMID- 2228121 TI - Carcinogens in our environment. PMID- 2228122 TI - Air pollution and cancer. AB - Epidemiological studies have shown increased lung cancer risks in urban areas and in communities near some types of industries, such as non-ferrous smelters. The excess relative risks are generally of the order of 50% or lower, which implies that uncontrolled confounding has to be considered in the evaluation. Extrapolations of risks associated with occupational exposures provide some support for the findings. For cancer of other sites, the data are less consistent. An increased precision in exposure estimation is desirable in future epidemiological studies on cancer related to ambient air pollution. PMID- 2228118 TI - A pilot study of detection of DNA adducts in white blood cells of roofers by 32P postlabelling. AB - To assess the utility of DNA adducts as biomarkers of exposure to carcinogens in an industrial population, a pilot study of roofers occupationally exposed to a mixture of polycyclic aromatic hydrocarbons was conducted. DNA was isolated from peripheral white blood cells of roofers and non-occupationally exposed subjects matched for age, sex and smoking status. Occupational exposures to anthracene, fluoranthene, pyrene, benzanthracene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[g,h,i]perylene and benzo[k]fluoranthene were assessed by personal breathing zone air sampling and skin wipes. Exposures to benzo[a]pyrene in air of exposed subjects ranged from 0.60 microgram/m3 to 1.39 micrograms/m3, and exposures to total polycyclic aromatic hydrocarbon (the sum of eight hydrocarbons) ranged from 6.0 micrograms/m3 to 13.8 micrograms/m3 on the day before blood collection. In the biomarker studies 10 of 12 roofers, but only 2 of 12 comparison subjects, had detectable levels of aromatic DNA adducts by 32P-postlabelling assay (p less than 0.01). The two non-roofers with detectable adducts had levels at or near the detection limit of 2 adducts per 10(9) nucleotides. In two roofer samples which were studied in a mixing experiment, the major adduct spots did not co-migrate with the guanosine N2 adduct of benzo[a]pyrene diol epoxide. These results suggest that the 32P-postlabelling assay may be useful for monitoring exposures to complex mixtures of aromatic hydrocarbons in industrial populations. PMID- 2228123 TI - Complex mixtures of urban air pollutants: identification and comparative assessment of mutagenic and tumorigenic chemicals and emission sources. AB - Current research on the cancer risks of complex mixtures of urban air pollutants addresses the identification and comparative assessment of mutagenic and carcinogenic chemicals and emission sources. To identify genotoxic compounds in urban air, micromutagenesis methods are coupled to analytical fractionation and new chemical characterization methods. Among polar mutagenic compounds, many appeared to be nitrated and or oxygenated aromatic compounds. Source apportionment of the mutagenic activity observed in urban air shows that vehicles and residential heating are major contributors to the ambient mutagenicity of the aerosol fraction. Comparative tumorigenesis and DNA adduct dosimetry studies are also being conducted with these same combustion emission sources and urban aerosols. The potential hazard and sources of the gaseous emissions have not been determined, but appear to be significantly increased by atmospheric transformation by ozone and nitrogen oxides. PMID- 2228124 TI - Mutagenic activity of complex air pollutants in Silesia. AB - Continuous monitoring of air over the highly industrialized region of Silesia, Poland, shows high pollution with free sedimenting particulate matter, gaseous compounds and metals. Partial chemical analysis of extracts from airborne particulate material revealed over a hundred polycyclic aromatic hydrocarbons (PAHs); 15 major PAHs were evaluated quantitatively at 20 measuring points during summer and winter periods. Both direct and indirect mutagenic activity in extracts of particulate material was observed, with seasonal variations in activity. The direct mutagenic activity was higher in winter samples than in summer ones. Summer samples exhibited high mutagenic activity after metabolic activation of extracts. PMID- 2228125 TI - Mutagenicity of emission and immission samples around industrial areas. AB - Urban air particulates (suspended particles and settling dusts), as well as dusts emitted by a Soderberg aluminium production plant and a coal-burning power plant, in the industrial town of Ajka were analysed for polycyclic aromatic hydrocarbon (PAH) content (liquid chromatography) and mutagenicity (Salmonella microsome test). The same parameters for air particulates from Papa (a town of similar size without much heavy industry) were analysed and compared to those from Ajka. The dust content, PAH concentration and the mutagenic potency of the air in Ajka were higher than in Papa. Mutagenicity of airborne particulates showed a clear seasonality with a winter maximum and a summer minimum in both towns. The mutagenic potency of air correlated well with the benzo[a]pyrene (BP) and PAH content in Ajka but not in Papa. The amounts of extractable organic material and mutagenic potency, as calculated for unit quantity of airborne particulate matter, were higher in the Papa samples. Similar differences between the two towns were observed in the case of deposited dust. As regards the emission dusts, the aluminium plant emissions are responsible for much more of the mutagenicity of the urban air than the power plant emission, which is the main component of air dust pollution in Ajka. PMID- 2228126 TI - Statistical aspects of experimental studies with complex mixtures. AB - Some formal concepts are introduced relating to the statistical design and analysis of experiments with complex mixtures. Aspects relating to the chemical analysis of complex mixtures, identification of their major components, continuous monitoring of samples or related issues are not addressed. As a surrogate for experimental studies in general, the discussion is oriented towards the situation of long-term animal experiments. When complex mixtures of unknown components are to be tested, samples collected under a standardized protocol must be applied to the different exposure groups in such a way that the experimental groups differ only in the dose of the exposure they receive. If the composition of a mixture is known, selected components may be combined in experimental testing in order to study the nature of their joint effect. Careful consideration guided by a priori knowledge about the individual compounds' dose-response relationships is required to design and analyse such experiments. There is an apparent need to avoid confusion by unifying the terminology in this field. PMID- 2228128 TI - Genotoxicity of drinking waters. AB - Drinking waters in many countries have been shown to contain non-volatile polar mutagenic compounds as well as trihalomethanes. Their nature is uncertain, but one compound, a chlorinated furanone (3-chloro-4-(dichloro-methyl)-5-hydroxy 2(5H)-furanone;MX) seems to be responsible for one third to over one half of the mutagenicity. Its concentration seems to correlate rather well also with the total bacterial mutagenicity. Animal toxicity studies are being used to evaluate the possible carcinogenicity risk of this compound as a first stage in complete risk assessment of the whole complex mixture. Epidemiological risk assessment is also possible, since mutagenicity values can be predicted on the basis of organic material in the raw water and the amount of chlorine used. This information has been collected in Finland retrospectively from waterworks, and will be correlated with the Finnish Cancer Registry data. PMID- 2228127 TI - Drinking water and human cancer. AB - The relatively low concentrations of the various natural and man-made contaminants of drinking water, together with the methodological problems of obtaining valid and complete exposure histories for individuals and of controlling for confounding factors, have made it difficult for epidemiological studies to detect and estimate risks of cancer. Nearly all studies to date, with some exceptions for the halogenated hydrocarbons, have been at the ecological level. For these and other reasons, quantitative risk assessment of the cancer risks due to this complex environmental exposure remains rudimentary. If, eventually, risks are assessed to be non-trivial, primary prevention could be sought by alternative choices of either methods of water treatment or of water sources. However, since we cannot eliminate all trace carcinogens from our environment, we need simultaneously to minimize both the exposures and the biological impact of such exposures. The latter will require studies of cancer chemoprevention, using biochemical and molecular epidemiological approaches. PMID- 2228130 TI - Mutagenic compounds in chlorinated pulp bleaching waters and drinking waters. AB - A review is given of the isolation and identification of the extremely strong bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone, coded MX, in wood pulp chlorination waters in 1980. This compound is one of the most potent known mutagens, as determined by the Ames test. In 1986 this compound was found also in chlorinated drinking water. MX accounts for a substantial portion of the mutagenicity of chlorinated drinking waters. Several other compounds related to MX have recently been identified in chlorinated waters, such as the geometric isomer (E-MX), the oxidized and reduced forms of MX and the oxidized form of E MX. Brominated analogues of MX may be formed by chlorination in the presence of bromide ions. Unanswered questions pertaining to the chemistry and genotoxicity of MX and related chlorinated mutagens are examined. PMID- 2228129 TI - Toxicity and mutagenicity of a mixture of 25 chemicals found in contaminated groundwater. AB - A defined mixture of 25 chemicals that are often found in contaminated groundwater was prepared as an aqueous solution and studied for mutagenicity in bacteria, for prophage induction in bacteria, for palatability and effect on weight-gain in rats and mice, and for cytogenetic effects in bone marrow cells of rats and mice. The bacterial mutation and prophage induction tests were negative. Exposure to the mixture in drinking water for two weeks resulted in a concentration-related decrease in water consumption in male and female rats and mice. Concentration-related decreases in weight gain were observed in male and female mice; in rats, only the high-dose groups showed decreased weight gains. A small but significant increase in sister chromatid exchanges was seen in male mice and a similar weak effect on micronucleated polychromatic erythrocytes (PCE) in the bone marrow of males and females. Also in bone marrow of male and female mice, an increase in mitotic index and a decrease in average cell generation time was observed. The %PCE in bone marrow was decreased in female mice only, while the %PCE in peripheral blood was increased in both sexes. In rats, the only effects observed in the cytogenetic studies were increased PCE frequencies in the peripheral blood of males and in the bone marrow of males and females. These results indicate that the 25-chemical mixture studied is not genotoxic in bacteria and that a concentration-dependent effect on its palatability to rodents leads to reduced water consumption, food consumption and weight gain. Although the bone marrow effects may be associated with disruptions of normal erythropoiesis that, in turn, alter the cytogenetic end-points reported, elevations of SCE and MN-PCE in mice suggest the 25-chemical mixture, under the conditions of administration, leads to cytogenetic damage in the bone marrow. Such damage may indicate a potential health hazard. PMID- 2228132 TI - Interaction between human carcinogens. AB - In the absence of direct information on the carcinogenicity of a complex mixture, assessment of its risk requires not only knowledge of the risks due to the separate components, but also assumptions about the interaction between the components. A formal definition of interaction is given, followed by a discussion of the theoretical basis for different kinds of interactions. Epidemiological studies which have considered the simultaneous effect of two chemical carcinogens are reviewed, and shown to provide examples of additivity, multiplicativity and interaction both intermediate between the two and greater than multiplicative. Finally, implications for the risk assessment of mixtures are discussed. PMID- 2228131 TI - Environmentally stable chlorinated contaminants from the pulp and paper industry. AB - Toxic polychlorinated dioxins and dibenzofurans have been identified in effluents and products from pulp and paper mills using chlorine bleaching. The amounts and levels depend on the bleaching technique used and the product quality. The same compounds have also been identified in sediment samples and aquatic organisms collected in the vicinity of pulp mills. The highest levels were found in hepatopancreas from crustaceans. Much higher levels of alkyl-substituted polychlorodibenzofurans have been found in sediment and sludge samples. PMID- 2228133 TI - Carcinogenicity and mutagenicity of the shale-oil produced in the Estonian Kiviter retort. AB - Skin painting experiments in CC57Bl mice showed that the total oil (TO) obtained by thermal processing of lump oil shale in the high capacity 'Kiviter' retort containing 56 ppm benzo[a]pyrene (BP) and diluted with benzene (66.6%) induced skin tumours in five out of 60 effective mice--in three mice squamous-cell papillomas and in two mice carcinomas. The light fraction (230-350 degrees C) of this oil and the laboratory residue (82 ppm BP) of the latter failed to induce skin tumours. An industrial residue of a blend of shale oils containing 590 ppm BP induced in 10 mice papillomas and in three mice carcinomas, gave a positive response in the Ames assay and also induced chromosome aberrations and sister chromatid exchanges. The laboratory residue and light fraction were clearly mutagenic in the Ames assay and positive responses were also obtained with the basic and neutral fractions and a polynuclear aromatics fraction. PMID- 2228134 TI - Estimated risk of lung cancer attributable to occupational exposures in iron and steel foundries. AB - Elevated risks of lung cancer have been observed in foundry workers in a number of studies. When the levels of exposure were compared with other industries, the most probable causes of the lung cancer excess were polynuclear aromatic compounds (PACs) and silica in iron foundries and PACs, silica, as well as chromium and nickel fumes in steel foundries. PMID- 2228136 TI - Assessment of exposure to genotoxicants in a foundry. AB - The mutagenicity of acetone extracts of airborne particles sampled during two seasons at different work sites in a foundry and of foundry workers' urine concentrates was determined by the Salmonella plate incorporation assay. In general, the ambient concentration of particles did not correlate with the air mutagenicity at different work sites. The considerable seasonal variation in the mass concentration of fumes and/or dust and in the airborne particles and air mutagenicity, was apparently related to changes in the intensity of work at some work sites. Because of confounding with smoking, urine mutagenicity was not found suitable for assessment of individual exposure, even though at a group level some correlation in mutagenicity was observed between the air at specific work sites and the workers' urine. PMID- 2228135 TI - Definition of exposure in epidemiological studies on foundry workers. AB - Epidemiological analytical studies investigating lung cancer risk among foundry workers are reviewed in relation to the available information on exposure. Nine studies (eight historical cohorts and one case-control) have been included. Overall, the information on exposure was poor. In none of the studies were there industrial hygiene measurements for investigating dose-response relationships, while duration of employment was the most common proxy of exposure utilized. None of the studies made an attempt to construct job-exposure matrices. The interpretation of the evidence in causal terms appears mainly based on the consistency across studies of the increased lung cancer mortality rather than on the relationship between the exposure in the working environment and the excess mortality reported. PMID- 2228137 TI - Cancer epidemiology in the paper and pulp industry. AB - Several studies of pulp and paper workers have demonstrated increased risks for certain cancer sites, e.g. tumours of the lymphatic and haematopoietic system as well as stomach cancer. An impressive lung cancer excess was found among paper and board mill workers in Finland, but not in studies elsewhere. Individual exposures have not been estimated, neither has a job-exposure matrix been applied in any of the studies. Therefore, it is impossible to link any of the excesses to specific single compounds or mixtures, of which there are a multitude in the pulp and paper industries. Although there are high quantities of organic chlorine compounds in the process mixtures and waste, the compounds have low volatility and occupational exposures are not necessarily high. Estimations of individual occupational exposure should be mandatory in future epidemiological studies in this industry. PMID- 2228139 TI - Food as source of complex mixtures of mutagens and carcinogens. PMID- 2228140 TI - Chemistry and biological activity of volatile and nonvolatile mutagenic compounds from cooked food. AB - Cooking fumes constitute a major part of the mutagenic activity detected in indoor air samples. The chemical nature of the smoke mutagens has not been determined, but existing data indicate the presence of carcinogenic heterocyclic amines, previously identified in crust and pan residue from fried meat. Reports on the chemical nature and biological activity of these compounds are reviewed. PMID- 2228138 TI - Complex chlorinated hydrocarbons: occupational exposure in the sawmill industry. AB - Exposure to chlorophenols occurs in the vicinity of the lumber treatment area in sawmills and in subsequent work phases where treated lumber is handled. Measurements from several countries indicate that the concentration of chlorophenols in the workroom air is generally below 0.5 mg/m3, the occupational exposure limit of chlorophenols in many countries. Inhalation usually leads to relatively low concentrations of chlorophenols in urine of exposed workers. Frequent skin contact with chlorophenol solution or with freshly treated lumber can produce urine concentrations 10-100 times higher than among those with inhalatory exposure only. In addition to chlorophenols, exposure to toxic polychlorinated dibenzodioxins and dibenzofurans may occur in some tasks carried out in sawmills. Jobs with potentially heavy exposure include the treatment of dipping-vat sludge and processes involving heating of chlorophenols, such as burning of treated waste wood and welding of metal structures contaminated by chlorophenols. PMID- 2228141 TI - Dietary influences on urinary excretion of hydroxyphenanthrenes, thioethers and mutagenicity in man. AB - Our study indicates that large differences in dietary polycyclic aromatic hydrocarbon (PAH) content in humans are not reflected by urinary and faecal excretion of hydroxyphenanthrenes, although significant increases in 3 hydroxybenzo[a]pyrene and 3-hydroxychrysene in faeces were observed after consumption of a diet rich in PAHs. The question therefore arises whether urinary hydroxyphenanthrenes are a reliable marker for exposure to PAHs. As expected, the elevated mutagenicity of the diet rich in PAHs led to increased mutagenic activity in urine. The increased urinary excretion of thioethers after this diet was probably due to its higher thioether content. Therefore, an elevated thioether excretion does not always indicate exposure to electrophilic compounds. PMID- 2228142 TI - Linear relationship between DNA adducts in human lung and cigarette smoking. AB - Human lung and bladder DNA has been isolated and purified from either surgical or autopsy specimens. Smoking history details were obtained from patients or their close relatives. Each DNA sample was investigated using the nuclease P1 digestion modification of the 32P-postlabelling procedure. Data are presented for 48 lung and 19 bladder specimens. The samples were subdivided into three groups for data analysis, viz. smokers, former smokers and nonsmokers. The mean adduct levels (adducts per 10(8) nucleotides) in lung samples were: [see text] The chromatographic pattern of bladder DNA adducts for smokers was similar to that for smokers' lung DNA, although less intense. Adduct levels in former smokers tended to be lower than in smokers, although loss of adducts appeared to require several years after cessation of smoking. These findings support a link between DNA adduct levels and cigarette smoking, for both the lung and the bladder. For the former tissue there was a strong linear correlation between adduct levels and the number of cigarettes smoked. PMID- 2228143 TI - Mouse skin tumours and human lung cancer: relationships with complex environmental emissions. AB - Mouse skin tumorigenesis has often been used to evaluate the tumorigenic effects of complex mixtures, including human respiratory carcinogens. This study examines the quantitative relationships between tumour induction in SENCAR mouse skin and the induction of respiratory cancer in man using four well established human respiratory carcinogens: emissions from coke ovens, roofing tar pots, diesel engines, and cigarettes. The tumour multiplicity data from mouse skin studies using extracts of particulates from each of the four emission sources are compared and their relative potencies to the coke oven sample are: coke oven:roofing tar:diesel:cigarette smoke condensate; 1.0:0.20:0.15:0.0011. Using the unit risk (the lifetime probability of respiratory cancer death due to a constant lifetime exposure of 1 microgram/m3 emissions in the inhaled air) to compare the potencies of the four emissions to human respiratory cancer, the relative potencies are: coke oven:roofing tar:diesel:cigarette smoke: 1.0:0.39:0.075:0.0024. When fitted to a linear regression, the mouse skin tumour data and human lung cancer risks were highly associated, with a correlation constant of 0.95 and a slope value of 0.89. The close association suggests that this comparative potency approach can be used in prospective analyses of human respiratory cancer risk to complex emissions, and several examples are proposed. In addition, the similarity of the chemical and toxicological characteristics of complex mixtures is discussed with regard to the prospective use of the comparative potency approach. PMID- 2228144 TI - Screening assays for carcinogenic agents and mixtures: an appraisal based on data in the IARC Monograph series. AB - To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans and which types of short-term test are more relevant for predicting human hazards, an analysis was performed on agents that were evaluated in IARC Monographs Supplements 6 and 7 for their carcinogenic effects in humans and animals and for activity in short-term genotoxicity tests. The prevalence of genotoxicity among four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 66) was determined. Each of the groups 1, 2A and 2B contained a high proportion (80 90%) of genotoxic carcinogens, which were also multi-species or multi-tissue carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and many in group 3. Although limited by the data-base available through the Monographs series, this analysis implies that genotoxic carcinogens add more to the human cancer burden than non genotoxic carcinogens. Thus, the continued use of in vitro/in vivo short-term tests, involving as endpoints DNA chromosomal or mutational damage, to identify genotoxic carcinogens or in the isolation of carcinogenic components in complex mixtures is fully justified. It is concluded that (a) an agent or complex mixture with unknown carcinogenic potential showing sufficient evidence of activity in genotoxicity assays in vitro or in vivo is likely to represent a hazard to humans and (b) an agent or complex mixture showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity for rodent bioassay, in view of the present lack of validated short-term tests for non genotoxic carcinogens. PMID- 2228146 TI - The use of short-term tests in detecting carcinogenicity of complex mixtures. AB - Since it is not feasible to test all substances in long-term animal studies, short-term tests for DNA damage, gene mutation, aneuploidy, chromosomal damage and cell transformation performed in prokaryotes and eukaryotes in vitro and in vivo are used to test pure chemicals and mixtures. Understanding the contribution of mutagens in air, water and food is important to our way of life; methods of sampling and testing such mutagens are discussed in this review. PMID- 2228145 TI - Genetic activity profiles--application in assessing potential carcinogenicity of complex environmental mixtures. AB - Some knowledge of the potential genetic activity of a complex environmental mixture may be gained from an assessment of the genetic activity of its component chemicals. The expanded genetic activity profile (GAP) data-base provides a computer-generated graphic representation of genetic bioassay data as a function of dose of the substance tested. In addition, the atmospheric chemical compound (ACC) data-base contains information on chemical structures, properties, detection methods and sources of chemicals found in ambient air. Using the combined data-bases, information on the quantity of an individual chemical present within a mixture or fraction of a mixture may be related to the quantity (lowest effective dose; LED) of the chemical required to demonstrate a positive response in one or more genetic bioassays. Alternatively, quantitative information on the carcinogenic potency of each individual compound (TD50 value) may be related to the quantity present in the mixture or mixture fraction and used to calculate the percent human exposure dose/rodent potency dose (HERP) for the chemical. Using an additivity assumption, a conservative estimate of potential carcinogenic hazard for the mixture may be calculated based on the HERP indices for its chemical components. This conceptual approach is limited by the relatively small number of chemicals identified in complex mixtures for which genetic toxicology and animal cancer data exist. PMID- 2228147 TI - Close correlation of intra-abdominal fat accumulation to hypertension in obese women. AB - The relation between intra-abdominal visceral fat accumulation and blood pressure was investigated in 67 obese women (mean body mass index, 33.6 +/- 3.1; average age, 50 +/- 11 years). As an index of intra-abdominal fat accumulation, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area was determined using a computed tomographic section at the level of the umbilicus. When the obese subjects were divided into a hypertensive group and a normotensive group, the ratio of the intra-abdominal visceral fat area to subcutaneous fat area in the hypertensive group was significantly higher (0.53 +/- 0.33 versus 0.29 +/- 0.12, p less than 0.01). Significant correlations between the ratio of intra abdominal visceral fat area to subcutaneous fat area and systolic blood pressure (r = 0.62, p less than 0.001) and diastolic blood pressure (r = 0.53, p less than 0.001) also were found. However, no significant difference existed in either the body mass index or the waist-to-hip circumference ratio between the hypertensive and normotensive groups. Plasma renin activity, aldosterone, epinephrine, and norepinephrine levels were not significantly different between the two groups. Moreover, the correlation between the ratio of the intra-abdominal visceral fat area to subcutaneous fat area ratio and blood pressure was found independent of age and body mass index by multiple regression analyses. We conclude that intra abdominal fat accumulation itself may play an important role in the pathogenesis of hypertension in obesity. PMID- 2228148 TI - Early 24-hour blood pressure elevation in normotensive subjects with parental hypertension. AB - Subjects with a family history of parental hypertension are reported to have a slightly higher office blood pressure in the prehypertensive stage. Whether this reflects a hyperreactivity to blood pressure measurement or a more permanent blood pressure elevation, however, is not known. In the present study, blood pressure was measured in 15 normotensive subjects whose parents are both hypertensive (FH++), 15 normotensive subjects with one hypertensive parent (FH(+) ), and 15 normotensive subjects whose parents are not hypertensive (FH--); among the three groups, subjects were matched for age, sex, and body mass index. The measurements were made in the office during a variety of laboratory stressors and during a prolonged resting period, and for a 24-hour period (ambulatory blood pressure monitoring). Office blood pressure was higher in the FH++ group than in the FH-- group (p less than 0.05). The pressor responses to laboratory stressors were similar in the two groups, but the FH++ group had higher prolonged resting and 24-hour blood pressure than the FH-- group; the difference was always significant (p less than 0.05) for systolic blood pressure. The FH++ group also had a greater left ventricular mass index (on echocardiographic examination) than the FH-- group (p less than 0.01). The blood pressure values and echocardiographic values of the FH(+)- group tended to be between those of the other two groups. Thus, the higher blood pressure shown by individuals in the prehypertensive stage with a family history of parental hypertension does not reflect a hyperreactivity to stress but an early permanent blood pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228149 TI - Inheritance of hypertension and blood pressure reactivity. PMID- 2228150 TI - Exercise tolerance and alcohol intake. Blood pressure relation. AB - The relations of systolic and diastolic blood pressures to alcohol intake and exercise tolerance levels in 15,612 men and 3,855 women were investigated. Alcohol intake was assessed by questionnaire and stratified into seven levels for men and six for women according to the ounces of ethanol consumed per week. Exercise tolerance was determined by maximal treadmill exercise testing and was categorized into six age-specific by sex-specific levels. Both systolic and diastolic blood pressure were significantly related to both alcohol intake and exercise tolerance levels in both men and women. These relations, which were positive for alcohol and negative for exercise tolerance, remained after covariance adjustment for age, body mass index, and cigarette smoking. Alcohol intake was not significantly correlated with exercise tolerance. The relation of blood pressure to alcohol was not linear because the blood pressure of moderate consumers of alcohol tended to be slightly lower than that of nondrinkers. Higher blood pressure was found only in drinkers whose ethanol intake exceeded 9.5 ounces (approximately 285 ml or 19 drinks) per week. However, heavy drinkers in high exercise tolerance categories had no higher blood pressure than nondrinkers in low exercise tolerance groups. Exercise tolerance or physiological fitness appears to be important in quantifying the relation between alcohol intake and blood pressure and should be considered in describing this relation. PMID- 2228151 TI - Red blood cell Na+ transport as a predictor of blood pressure response to Na+ load in young blacks and whites. AB - The present study was designed to investigate the role of abnormalities in red blood cell sodium-potassium-chloride (Na-K-Cl) cotransport and Na+ pump as predictors of the pressor response to chronic oral Na+ loading in young whites and blacks. Subjects were healthy adults from 18 to 23 years of age and included normotensive whites (n = 24) and normotensive blacks (n = 35). Red blood cell transport studies were performed before Na+ loading. The Na+ load consisted of 10 g NaCl daily added to the usual diet. A sodium-sensitive response was defined as an increase of 5 mm Hg or more in mean arterial pressure after the Na+ load; a sodium-insensitive response was a less than 5 mm Hg increase in mean arterial pressure. A sodium-sensitive response occurred in 16% of whites and 57% of blacks. Black subjects have a significantly lower (p less than 0.005) maximal rate of furosemide-sensitive Na+ efflux and a higher Km for cellular Na+ (p less than 0.05) to activate Na-K-Cl cotransport than white subjects. Normotensive blacks with sodium-sensitive blood pressure response had a higher Km (14.4 +/- 6 mmol/l cell, n = 17, mean +/- SD) to activate the cotransport than sodium insensitive blacks (9.9 +/- 3.7 mmol/l cell, n = 13, p less than 0.001). Normotensive whites had a significantly lower red blood cell Na+ content (p less than 0.05) and a higher maximal rate of cotransport (p less than 0.005) than young normotensive blacks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228152 TI - Calcitropic hormones, platelet calcium, and blood pressure in essential hypertension. AB - Plasma ionized calcium, platelet cytosolic calcium (using the fura-2 method in gel-filtered platelets), parathyroid hormone (both the intact hormone and a midmolecule portion), calcitriol, and calcidiol were measured in 19 untreated male patients with essential hypertension and 19 age-matched normotensive male research subjects. Mean levels of platelet cytosolic calcium, parathyroid hormone, calcitriol, and calcidiol were all significantly higher, whereas plasma ionized calcium was significantly lower, in the hypertensive group compared with the normotensive group. Both platelet cytosolic calcium and intact parathyroid hormone were positively correlated with mean arterial pressure (r = 0.58, p less than 0.001; r = 0.54, p less than 0.001, respectively), whereas plasma ionized calcium was inversely correlated with mean arterial pressure (r = -0.60, p less than 0.001) in the combined group of all study subjects. All three of these correlations were significant in the hypertensive group alone but not in the normotensive group alone. When analyzed with plasma ionized calcium, body mass index, serum calcitriol, and calcidiol in a multivariable regression model, the significance of the partial regressions of platelet cytosolic calcium and parathyroid hormone with mean arterial pressure persisted. Intact parathyroid hormone was positively correlated to platelet cytosolic calcium (r = 0.43, p less than 0.01) and plasma ionized calcium was inversely correlated to platelet cytosolic calcium (r = -0.44, p less than 0.01). These results confirm previous reports of disturbances of calcium metabolism in essential hypertension and suggest that the elevated platelet cytosolic calcium observed in essential hypertension may be linked to one or more of these alterations of calcium metabolism. PMID- 2228153 TI - Injection of 1,25-(OH)2 vitamin D3 enhances resistance artery contractile properties. AB - The hypothesis that 1,25-dihydroxyvitamin D3 [1,25-(OH)2 vitamin D3] modulates vascular smooth muscle contractile function was tested. 1,25-(OH)2 vitamin D3 (50 ng/day) was administered by intraperitoneal injection over a 3-day period to 13 15-week-old male spontaneously hypertensive and Wistar-Kyoto normotensive rats. On the fourth day, serum was prepared and contractile force generation of isolated mesenteric resistance arteries was examined. Treatment with 1,25-(OH)2 vitamin D3 approximately doubled serum levels of the hormone and increased ionized and total serum Ca2+ and phosphate by 5-10%. No effect on blood pressure was detected. 1,25-(OH)2 vitamin D3 injection in both strains enhanced maximal stress generation to norepinephrine and serotonin by 30-40%, with no effect on apparent sensitivity of the vessels to the agonists. To assess the effect of a maneuver that elevates serum ionized Ca2+ without the addition of exogenous hormone, maximal stress generation was examined in resistance arteries isolated from rats fed diets containing 0.5% or 2% calcium over a 6-7-week period. Maximal stress generation in response to norepinephrine was greater in vessels from rats of both strains maintained on 0.5% calcium. It is concluded that 72-hour in vivo treatment with 1,25-(OH)2 vitamin D3 increases contractile force-generating capacity of resistance arteries without affecting blood pressure. It is proposed that this action of 1,25-(OH)2 vitamin D3 is the result of a direct action of the hormone on the vascular wall. PMID- 2228154 TI - Does antihypertensive therapy improve the function of the vascular endothelium? PMID- 2228155 TI - Enalapril and renal injury in spontaneously hypertensive rats. AB - Rats of the spontaneously hypertensive strain develop kidney damage that resembles the nephropathy seen in some cases of human essential hypertension. Previous studies with a triple drug antihypertensive regimen indicated that proteinuria and glomerular histopathology in spontaneously hypertensive rats might develop despite long-term effective control of systemic blood pressure. To investigate further the relation between hypertension and kidney disease, a group of spontaneously hypertensive rats were treated with enalapril at 15 weeks of age. Blood pressure, protein excretion, and kidney function were measured in those rats at regular intervals during the next year and a half and were compared with untreated spontaneously hypertensive rats and the normotensive Wistar-Kyoto parent strain. Kidney tissue samples from all three groups, collected at autopsy, were stained by immunohistochemical and conventional methods to assess the relative severity and nature of kidney damage. Although enalapril therapy was completely effective in controlling the blood pressure of spontaneously hypertensive rats, it only postponed the onset of kidney disease. Enalapril treated spontaneously hypertensive rats eventually exhibited albuminuria as severe as that found in hypertensive rats. Kidney vessel pathology was completely prevented with enalapril, but the abnormal accumulation of mononuclear cells in tubulointerstitial and periglomerular sites was the same as in untreated spontaneously hypertensive rats. We have concluded that elevated protein excretion in rats of the spontaneously hypertensive rat strain is not a secondary consequence of systemic hypertension. Structural abnormalities of renal vessels also do not appear to contribute significantly to the pathogenesis of albuminuria in spontaneously hypertensive rats. Other explanations must be sought to account for the close link between spontaneous hypertension and kidney damage in this animal model. The clear dissociation of kidney disease from systemic hypertension exhibited by spontaneously hypertensive rats may also be relevant for human disease. PMID- 2228156 TI - Intrarenal de novo production of angiotensin I in subjects with renal artery stenosis. AB - To estimate the renal extraction and de novo production of angiotensin I and to assess the contribution of blood-borne renin to renal angiotensin I production, the aortic and renal venous plasma levels of renin and intact [125I]angiotensin I and endogenous angiotensin I during continuous systemic intravenous infusion of monoiodinated [125I]angiotensin I were measured in subjects with unilateral renal artery stenosis (n = 8) who were treated with captopril (50 mg b.i.d.). Results demonstrated that 80% of angiotensin I delivered by the renal artery was extracted both by the affected and the unaffected kidney and that on both sides a major part of angiotensin I in the renal vein was derived from intrarenal de novo production. Production of plasma angiotensin I was in excess over extraction (p less than 0.01) on the affected side, whereas extraction was in excess over production (p less than 0.01) on the contralateral side. The plasma level of de novo intrarenally produced angiotensin I in the renal vein was seven times higher on the affected side than the contralateral side. This difference was by far too big to be explained by a difference in the transit time of blood between the two kidneys, by an augmented production of angiotensin I in the circulating blood passing through the affected kidney due to the higher level of venous plasma renin activity in that kidney, or by the combination of both.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228157 TI - Effects of salt, race, and hypertension on reactivity to stressors. AB - Blood pressure and heart rate reactivity to a psychological stressor and to a cold pressor test were examined in a group of 51 normotensive and 37 unmedicated hypertensive men. All were studied twice, once while the participants were maintained on a moderately high salt (200 meq sodium/day) diet and once while the participants were maintained on an extremely low salt (10 meq sodium/day) diet. Dietary salt had no effect on blood pressure or heart rate responses to the two stressors. The systolic and diastolic responses of the white participants to the psychological stressor were greater than those of the black participants (both p less than 0.05); however, there was no difference between blacks and whites in reactivity to the cold pressor challenge. As compared with the normotensive group, the hypertensive group reacted to the psychological stressor with increased responses in systolic blood pressure, diastolic blood pressure, and heart rate (all p less than 0.05). The hypertensive group also hyperresponded in terms of the systolic pressure response to the cold pressor task (p less than 0.05). Plasma norepinephrine and epinephrine responses were not significantly different across the two diets, races, or diagnoses. PMID- 2228159 TI - Update: Recommendations for human blood pressure determination by sphygmomanometers. PMID- 2228158 TI - Pressor systems in hypertension and congestive heart failure. Role of vasopressin. AB - Elevated peripheral vascular resistance, which characterizes hypertension and congestive heart failure (the latter regardless of absolute blood pressure level) is maintained to a large extent by the combined effects of three major neurohormonal pressor mechanisms: the renin-angiotensin system, the sympathoadrenal system, and arginine vasopressin. Blockade of one of these mechanisms may lead to compensatory stimulation of the others, thus offsetting in part the hemodynamic benefits of a specific intervention. Combination therapy, designed to attack all three systems (with use of an angiotensin converting enzyme inhibitor, a sympathetic blocker such as clonidine, and an antagonist of the vasopressor action of vasopressin), may help in the treatment of such cases. To illustrate this strategy, two experimental studies, one case of malignant hypertension, and one case of congestive heart failure are presented. PMID- 2228161 TI - Gastroesophageal reflux disease. PMID- 2228162 TI - Pathophysiology of gastroesophageal reflux. Lower esophageal sphincter dysfunction in gastroesophageal reflux disease. AB - LES dysfunction is the principal mechanism responsible for GER disease. Two main patterns of sphincter dysfunction have been identified: an abnormally high rate of transient LES relaxations, and defective basal LES pressure. Overpowering of a weak LES by pressure transients induced by straining is less common than previously thought, at least under conditions tested thus far. Current evidence suggests that LES dysfunction results primarily from defective neural control, although smooth muscle function may also be impaired. Extrinsic mechanisms, particularly the diaphragmatic crura, also appear to be important during straining. The role of hiatus hernia remains unclear but seems likely to contribute to the pathogenesis of reflux disease by impairing LES function. PMID- 2228163 TI - Esophageal motor activity and acid clearance. AB - Esophageal acid clearance normally occurs as a two-step process. The initial step of emptying most of the fluid volume contained within the esophagus occurs quickly by gravity or by one or two peristaltic sequences. However, volume clearance is distinct from acid clearance, and esophageal pH is restored to normal after volume clearance as the 1 mL or so of residual acid is neutralized by swallowed saliva in a stepwise fashion. A considerable body of evidence has accumulated suggesting that about half of patients with reflux disease have markedly prolonged acid clearance times. Within this group abnormalities or both volume clearance and salivation have been demonstrated. Volume clearance may be impaired as a result of a breakdown of the peristaltic mechanism commonly seen with severe esophagitis or by "re-reflux" of cleared fluid from within a hiatal hernia. Either way, the result is increased residual acidic fluid within the esophagus. The increased residual acid must be titrated with saliva that has so slight a neutralizing capacity that it takes about 7 minutes for the average person to secrete enough saliva to titrate 1 mL of 0.1 N HCl. Salivation itself is reduced in cigarette smokers and in patients using anticholinergic medications, thereby prolonging the process of mucosal neutralization in such persons. Whatever the mechanism of prolonged acid clearance for a particular individual, the overall result is of prolonged esophageal mucosal acid exposure, which makes the development of peptic esophagitis more likely. PMID- 2228160 TI - Current concepts of the antireflux barrier. AB - The lower esophageal sphincter, crural diaphragm, and phrenoesophageal ligament are the anatomic structures that constitute the antireflux barrier. The intraluminal pressure at the esophagogastric junction (EGJ) reflects the strength of the antireflux barrier. The end-expiratory pressure is a result of the tonic activity of the smooth muscles of the lower esophageal sphincter. The EGJ pressure increases during inspiration owing to the effect of the crural diaphragm. There is a reflex increase in the EGJ pressure during periods of increased intra-abdominal pressure, and the crural diaphragm contributes to this reflex contraction of the EGJ. Based on the contribution of the lower esophageal sphincter and crural diaphragm to the EGJ pressure, a two sphincter hypothesis of the antireflux barrier competence is suggested. PMID- 2228164 TI - Esophageal mucosal resistance. A factor in esophagitis. AB - The development of esophageal damage depends on a number of factors. The components in the refluxate, including H+ ion, pepsin, bile salts, and pancreatic enzymes, are able to permeate the mucosa and cause injury. These agents may act individually or in combination. Balancing the effects of these damaging agents is the "esophageal mucosal barrier." This barrier is an integrated complex of anatomic and physiologic components that acts to maintain the integrity of the mucosa. Although the relative efficacy of the various components in developing an effective barrier is not understood completely, their physiologic and clinical importance in the face of "noxious" luminal contents remains critical. Understanding the interplay between the injurious agents in the refluxate and the esophageal mucosal barrier may allow for the development of new therapeutic measures in the treatment and prevention of gastroesophageal reflux disease. PMID- 2228167 TI - Pediatric gastroesophageal reflux disease. AB - Gastroesophageal reflux is a recognized clinical problem in infancy. To a great extent it represents a normal behavior that improves with maturation. The identification of appropriate candidates for medical and surgical therapy of GER during infancy is difficult and deserves further study. There are few well conducted clinical trials of therapy for infantile GER that compare the usual drugs used for adults with GER. Moreover, medications currently licensed for adults are often not approved for pediatric use in the United States. Surgical therapy for GER should be reserved for infants with severe disease that does not respond to medical therapy. PMID- 2228165 TI - Medical and surgical conditions predisposing to gastroesophageal reflux disease. AB - Esophageal disease has been reported in 70% to 90% of patients with scleroderma, of whom nearly 50% will have reflux esophagitis. The combined motility disorder of low LES pressure and aperistalsis of the esophageal body makes scleroderma patients especially susceptible to severe gastroesophageal reflux disease (GERD). Symptomatic GERD is a common problem in pregnancy, affecting 30% to 50% of women. Hormonal effects of estrogen and progesterone likely promote GERD by compromising LES function. Fortunately, the problem is usually relieved with delivery of the baby. Although difficult to quantitate, the reflux of both acid and especially alkaline material may be a common sequela of many types of gastric surgery. Medical therapy binding bile salts usually does not bring relief. The Rouxen-Y biliary diversion operation is the best solution for this problem. GERD complicates the treatment of achalasia after 10% of Heller myotomies and 2% of pneumatic dilatations. Nearly 50% of patients with the Zollinger-Ellison syndrome have esophagitis, which may be more difficult to treat than their ulcer disease. PMID- 2228166 TI - The spectrum of the symptoms and presentations of gastroesophageal reflux disease. AB - The symptoms and presentations of gastroesophageal reflux disease are rather numerous. These include the typical symptoms, such as heartburn, regurgitation, water brash, or dysphagia. However, reflux may also be responsible for such symptoms as hoarseness, pulmonary aspiration, or asthma. It may also be an important cause of noncardiac chest pain. Thus, gastroesophageal reflux disease may be considered a disease with more than just "esophageal" symptoms. PMID- 2228168 TI - Esophageal pH monitoring. AB - In the 25 years since it was first described, prolonged esophageal pH monitoring has gained increasing acceptance and popularity as a diagnostic and research technique in GER disease. Some recent developments that have contributed to its attraction include compact portable recorders, computerized analysis, short monitoring periods, the good discriminant value of the simple measurement of percent monitoring time that pH is less than 4, and the symptom index, allowing correlation of symptoms with reflux events. Nevertheless, there remain areas of uncertainty with regard to reproducibility and the conditions of monitoring, in particular whether strict dietary control and controlled activity and posture are necessary. There is no universally accepted normal range of values, but it is now apparent that normal and abnormal GER are not appropriately differentiated by simply defining the upper limit of normal using a formula of the mean plus two standard deviations, so other statistical techniques have emerged. Indications for the technique include atypical symptoms, particularly noncardiac chest pain, respiratory symptoms, and, in young children, apneic attacks and recurrent vomiting associated with failure to thrive. The technique is having an impact on the assessment prior to, during, and after medical and surgical therapy for GER, as well as in helping to unravel the complexities of the pathogenesis of esophagitis. PMID- 2228169 TI - Ancillary tests in the diagnosis of gastroesophageal reflux disease. AB - This article reviews some of the diagnostic procedures for gastroesophageal reflux disease other than the procedures of choice, endoscopy and prolonged intraesophageal pH monitoring. The author discusses the roles of the acid perfusion (Bernstein) test, radiology, manometry, and radionuclide scintigraphy in the diagnosis and management of gastroesophageal reflux disease. PMID- 2228170 TI - Complications of reflux esophagitis and their medical management. AB - It is shortsighted to consider only the esophageal manifestations and complications of esophageal reflux. That such reflux can directly affect not only the lung but also the oropharynx and larynx, both by direct acid contact and reflex neurologic mechanisms, has been demonstrated repeatedly. The task of the future will be to place such reflux into perspective as it remains only one of many genetic and environmental factors associated with disparate and often confusing disease processes. PMID- 2228173 TI - [Focus on esthetic prototypes adopted for Branemark implants]. PMID- 2228171 TI - Barrett's esophagus. Current assessment and future perspectives. AB - Barrett's esophagus is a premalignant condition and must be suspected in any patient with signs and symptoms of chronic reflux esophagitis. This condition itself is asymptomatic, so maintaining a high index of suspicion is the key to diagnosis. This article reviews natural history, pathogenesis, prevalence, and clinical symptoms of Barrett's esophagus. Diagnosis, dysplasia, adenocarcinoma, and treatment are discussed. PMID- 2228175 TI - [New applications of echography in maxillo-facial pathology]. PMID- 2228174 TI - [Protection of donor sites]. PMID- 2228172 TI - Antireflux surgery. A surgeon's look. AB - With a reassessment of the antireflux barrier, we are gaining a better appreciation of the components of the barrier and their importance in preventing reflux. The GE valve in particular appears to play a key role in preventing reflux. With better understanding of the anatomy and function of the GE barrier, we should do a better job, both medically and surgically. The knowledge and new technology that are available should allow the surgeon to perform antireflux surgery with 95% good to excellent results with a minimum of morbidity. As our 15 to 20 year follow-up with a mean of 17.8 years shows, these good results will last over the long term. These observations should give the gastroenterologist confidence that antireflux surgery is highly effective for those patients who fail medical management. PMID- 2228176 TI - [Physiological techniques of complete denture design for musicians, wind instrument players]. PMID- 2228177 TI - [Marketing for dentists]. PMID- 2228180 TI - [Root recovering. Lateral sliding flap]. PMID- 2228178 TI - [Forced eruption, a clinical procedure: apropos of 2 clinical cases]. PMID- 2228179 TI - [Dental prevention. 10 years experience at the University of Montreal School of Dental Medicine]. PMID- 2228181 TI - [A socioeconomic strategy in orthodontic treatment]. PMID- 2228182 TI - [Guillaume van den Bossche. His "Historia Medica"--1639--and dental organotherapy]. PMID- 2228183 TI - [Diagnosis of risk in periodontology]. PMID- 2228185 TI - [Appointment management. Fundamental factors]. PMID- 2228184 TI - [Cervico-facial cutaneous lesions of dental origin]. PMID- 2228186 TI - [What is your diagnosis? Maxillary sinus neoplasm]. PMID- 2228187 TI - Medical teams, flying squads--the arguments revisited. PMID- 2228189 TI - Closed percutaneous K-wire stabilization for displaced fractures of the surgical neck of the humerus. AB - We report a series of 22 displaced fractures of the proximal humerus treated by percutaneous Kirschner wire stabilization. Poor results (69 per cent) in the older age group of patients is a reflection of the severity of the fracture and the difficulties of closed reduction. Reduction in a poor position in this series has led to a poor range of movement. Good functional results can only be expected with a good reduction. Experience of migration with smooth K-wires has resulted in a strong recommendation for the use of threaded pins. PMID- 2228188 TI - Medical teams for accidents and major disasters. AB - Recent major disasters within the United Kingdom have highlighted the role of mobile medical teams. A prospective study of 244 call-outs demonstrated that an experienced medical team can be mobilized rapidly and effectively in response to accidents and potential disasters. An accident flying squad reduced mortality in the severely multiply-injured patient by providing treatment at the scene of the accident in 234 patients. The argument supporting the development of flying squads for accidents and major disasters can be based on the objective evidence of their value rather than on their empirical and emotional appeal. PMID- 2228190 TI - Pugh nail system as a form of treatment for fractures of the proximal femur. AB - A retrospective study of the results of treatment of 177 patients who had sustained a fracture of the proximal femur was undertaken. The social background, type of injury, operation performed, duration of stay after operation, mortality and morbidity were recorded and compared with the results published by other workers. It is concluded that the Pugh sliding nail system adequately fixes most fractures of the proximal femur. It allows early postoperative mobilization and discharge to the home environment for most patients. The overall mortality and morbidity compares favourably with results published for the dynamic compression screw. Treatment of the elderly patient with a displaced subcapital fracture of the femoral neck remains a problem, due to the high incidence of failure of fixation. It may be that for this group of patients a primary hemiarthroplasty is the treatment of choice. A prospective study to resolve this issue is required. The cost of a Pugh nail is considerably less than that of a dynamic compression screw. PMID- 2228192 TI - Radial nerve lesions associated with fractures of the humeral shaft. AB - Radial nerve palsy associated with a fracture of the shaft of the humerus is a relatively common injury. Out of 91 radial nerve injuries, operated upon in the Neurosurgical University Clinic in Belgrade from 1979 to 1988, 37 were associated with fractures of the humeral shaft or their surgical treatment. These fractures were previously treated in other medical units. In all cases a microsurgical reconstruction of the radial nerve was done: an interfascicular neurolysis in 24 cases and interfascicular grafting in 13 cases. A useful functional recovery was obtained in 91.9 per cent of the cases. Timing of nerve exploration and repair, as a main problem, is discussed. PMID- 2228191 TI - Closed nailing of tibial shaft fractures. AB - A total of 98 tibial shaft fractures were internally fixed by closed intramedullary nailing. Twenty-seven of the fractures were open and 71 were closed. In 62 patients (67 per cent) the fracture was the consequence of road traffic accidents; 32 patients (35 per cent) had other skeletal and soft tissue injuries. All the fractures united with a good range of knee and ankle movements; no disuse atrophy was encountered. Most patients returned to work early. In 14 patients comminution of the fracture resulted in up to 2 cm of shortening. Eight tibial fractures had delayed union. It is concluded that tibial nailing is a safe method of treatment for unstable fractures and for patients with multiple injuries. PMID- 2228193 TI - Internal fixation of pubic symphysis diastasis with a tension banding technique. AB - We present the details of a method of internally fixing diastasis of the pubic symphysis with stout wires and a tension band which can be employed with speed and ease, through a minimal exposure or minimally extended laparotomy wound. The technique is suitable for those with little experience of internal fixation of the pelvis. Our initial cases are presented. PMID- 2228194 TI - Management of unreduced traumatic posterior dislocation of the hip: heavy traction and abduction method. AB - Eight cases of unreduced traumatic posterior dislocation of the hip were treated by heavy traction and abduction. In four out of eight cases a concentric reduction was obtained. In two patients where a concentric reduction was not obtained, open reduction was performed. In these patients, there was an excellent or good result. In the remaining two patients a non-concentric reduction was accepted, and they had poor clinical results. PMID- 2228195 TI - Motorcycle injuries in Bermuda. AB - Tourists who hire mopeds or motorcycles for personal use have a risk for accident. The incidence of tourist accidents in Bermuda was 1.57 accidents/1000 tourists evaluated over a 6-month period. The accident incidence increased as the tourist population got larger. Tourists of more than 40 years of age had the greatest increase in incidence for accident during this period. The risk of an injury requiring hospital stay was one patient for every 16,000 tourists visiting the island, and usually involved the fracture of an extremity. All accidents, major or minor, resulted in some form of skin injury. PMID- 2228196 TI - Pilot study of injured patients seen in the University of Port Harcourt Teaching Hospital, Nigeria. AB - A 12-month pilot study of injured patients seen in the Emergency Department of the University of Port Harcourt Teaching Hospital was carried out. Trauma (28.8 per cent) was the main reason for emergency visits; 82.1 per cent of the patients were under 31 years of age. Domestic accidents were the commonest cause of trauma (42.5 per cent), followed by criminally motivated injuries (30.4 per cent), road traffic accidents (26.0 per cent), industrial (0.5 per cent) and other accidents (0.6 per cent). The overall mortality rate due to trauma was 5.4 per cent and within the period of study, trauma was the most common cause of deaths in hospital (10.1 per cent). Road traffic accidents were responsible for 67.9 per cent of these deaths, followed by criminally motivated injuries (16.1 per cent). Domestic, industrial and boat accidents caused 7.6 per cent, 5.4 per cent and 3.1 per cent deaths, respectively. Injury Severity Scores (ISS) among 419 patients showed a 100 per cent mortality for those with scores above 35. There were 48 prehospital, 19 emergency room and 14 in-hospital deaths among patients with an ISS below 35. The deaths resulted largely from delayed transportation of victims to the hospital and partly from inadequate emergency medical services. To reduce the current high rate of preventable deaths from injury, we recommend (i) ambulance services for early transportation of victims to the hospital and (ii) improved emergency medical care. PMID- 2228198 TI - Tetanus complicating frostbite. PMID- 2228197 TI - Locked intramedullary nailing for recent lower limb fractures. AB - This paper reports the results in a prospective series of recent fractures of both the femur and tibia treated by the Grosse and Kempf locking system of intramedullary nailing. Although the technique requires some attention to detail, it has been possible to treat a wide range of relatively severe injuries with a short hospital stay and rapid rehabilitation, with benefit to both the patient and hospital services. PMID- 2228202 TI - Simultaneous avulsion of the long flexor and extensor tendons of a finger. PMID- 2228200 TI - Acute compression of the cervical spinal cord: a complication of preganglionic injury to the brachial plexus. PMID- 2228203 TI - Delayed small intestinal obstruction following blunt trauma to a Meckel's diverticulum. PMID- 2228199 TI - Thoracic disc protrusion in a patient with preganglionic injury of the brachial plexus: differential diagnosis of cord compression. PMID- 2228201 TI - A rare complication of a preganglionic brachial plexus injury. PMID- 2228204 TI - Spontaneous dislocation of the lunate in a weight lifter. PMID- 2228205 TI - Bilateral anterior glenohumeral dislocation in a weight lifter. AB - A case of bilateral anterior dislocation of the shoulder joint is described. The patient was a recreational weight lifter who sustained the injury while performing the 'pull-over' bench movement using free weights. Probably, the shoulders dislocated when the force developed by the periarticular muscles was less than the actual weight that the patient was trying to lift. The need for stricter safety rules and better supervision in health clubs is stressed. PMID- 2228206 TI - Dorsal subtalar dislocation of the foot. PMID- 2228207 TI - [Method of preparation of an individually programmed bracket system]. AB - Described is a method how brackets can be provided with individual bases by the means of a diagnostic set-up. Such a bracket system matches fully the individual tooth anatomies and the individually defined treatment objective, which is built into the appliance from the very beginning. PMID- 2228208 TI - [Modern functional and esthetic aspects of orthodontic surgery]. PMID- 2228210 TI - [Mandibular activation with rigid and elastic activators]. PMID- 2228209 TI - [Tooth mobility following treatment with removable appliances]. AB - After a therapy with removable appliances all the teeth showed an increased loosening degree, that means tooth mobility, in comparison to an untreated control group. All the measured patients had been in the retention phase after an average treatment time of 4 years in cases of male patients and 3.8 years in cases of female patients. PMID- 2228212 TI - [Adult treatment as therapy of dysfunction]. AB - Adult orthodontics often is to be considered as the prophylactic treatment for the disordered stomatognathic system. The enlarged facilities of diagnosis enable the orthodontist to investigate the reasons of the functional disorders, like neglected or insufficient orthodontic treatment in the growing patient or inconsiderate extractions. For many functional disorders with different reasons adult orthodontics is the causal therapy. Orthodontic treatment is also able to reduce the prosthetic therapy and to improve the prognosis for preserving the natural structures. Enlarged, continuous diagnosis and a high degree of postgraduate education must be required for successful adult treatment. PMID- 2228211 TI - [Growth of the facial skeleton and biomechanics of the stomatognathic system]. AB - Biomechanical analysis of the stomatognathic system yields that the linkage between posterior and anterior guidance can be modelled by a link quadrangle (throttle crank) with closed linkage. Within this gear system the biochemical ideal position of the couple-line (functional length of the mandible) possesses a special meaning in centric occlusion: Along this line the gear system can be stretched without altering its essential mechanical properties. Interindividual comparison of the arrangement of mandibulary and maxillary structures related to the ideal initial position of the couple-line presents interindividual constants of arrangement and of growth. It is possible to define an individual, non orthogonal system of coordinates. Its origin represents the individual center of growth. During growth special skeletally defined points run along radius vectors of this center. The rate of growth can depend on the angle between radius vector and couple-line. PMID- 2228213 TI - [Development of standard Edgewise apparatus for a pre-torqued and pre-angulated bracket system]. PMID- 2228216 TI - [Gaps in anterior region]. PMID- 2228215 TI - [PG-Universal retraction system. Theoretical aspects and clinical application. 1. Controlled cuspid retraction]. PMID- 2228214 TI - [Space closure with straight-wire apparatus]. PMID- 2228217 TI - [Long way of a third molar]. PMID- 2228218 TI - Regulation of magnitude of antibody response to bacterial polysaccharide antigens by thymus-derived lymphocytes. PMID- 2228219 TI - Partial biochemical characterization of cell surface hydrophobicity and hydrophilicity of Candida albicans. AB - Hydrophobic yeast cells of Candida albicans are more virulent than hydrophilic yeast cells in mice. Results of experiments performed in vitro suggest that surface hydrophobicity contributes to virulence in multiple ways. Before definitive studies in vivo concerning the contribution of fungal surface hydrophobicity to pathogenesis can be performed, biochemical, physiological, and immunochemical characterization of the macromolecules responsible for surface hydrophobicity must be accomplished. This report describes our initial progress toward this goal. When hydrophobic and hydrophilic yeast cells of C. albicans were exposed to various enzymes, only proteases caused any change in surface hydrophobicity. Hydrophobic cell surfaces were sensitive to trypsin, chymotrypsin, pronase E, and pepsin. This indicates that surface hydrophobicity is due to protein. Papain, however, had no significant effect. The hydrophobicity of hydrophilic cells was altered only by papain. The proteins responsible for surface hydrophobicity could be removed by exposure to lyticase, a beta 1-3 glucanase, for 30 to 60 min. When 60-min lyticase digests of hydrophobic and hydrophilic cell walls were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with a 12.5% resolving gel, each protein population contained a single unique protein that was not evident in the other protein population. However, when the cell wall surface proteins of hydrophobic and hydrophilic cells were first labeled with 125I and then removed by lyticase and analyzed by SDS-PAGE, at least four low-molecular-mass (less than 65 kilodaltons) proteins associated with hydrophobic cells were either absent or much less abundant in the hydrophilic cell digests. This result was seen for both C. albicans strains that we tested. When late-exponential-phase hydrophilic cells were treated with tunicamycin, high levels of surface hydrophobicity were obtained by stationary phase. These results indicate that the surface hydrophobicity of C. albicans reflects changes in external surface protein exposure and that protein mannosylation may influence exposure of hydrophobic surface proteins. PMID- 2228220 TI - Hyperoxia potentiates Ureaplasma urealyticum pneumonia in newborn mice. AB - The effect of continuous exposure to 80% oxygen on newborn mice with Ureaplasma urealyticum pneumonia was determined. Mice were inoculated intranasally with either U. urealyticum or sterile broth and then housed in either 80% oxygen or room air (21% oxygen). The mice were sacrificed at either 7 or 14 days after inoculation. Significantly more mice in the U. urealyticum group housed in 80% O2 than in the room air-exposed group were culture positive 14 days after inoculation (P = 0.042), but no difference was found at 7 days. The presence of alveolar macrophages, neutrophils, and lymphocytes and alveolar wall thickness were determined. Overall, the group housed in 80% O2 and inoculated with U. urealyticum had severe pulmonary lesions at both time points, while the lesion severity in the room air-exposed group inoculated with U. urealyticum and the group housed in 80% O2 and inoculated with sterile broth was dependent on the time point. Mortality was significantly higher in the group housed in 80% O2 and inoculated with U. urealyticum than it was in all other groups (P less than 0.001). Our results indicate that hyperoxia causes the persistence of U. urealyticum in the lungs of newborn mice, acutely potentiates the inflammatory response, and turns an otherwise self-limited pneumonia into a lethal disease. PMID- 2228221 TI - Aspergillus fumigatus complement inhibitor: production, characterization, and purification by hydrophobic interaction and thin-layer chromatography. AB - Aspergillus fumigatus has previously been shown to produce a soluble extracellular inhibitor of the alternative complement pathway, called Aspergillus complement inhibitor, or CI. We now report an efficient method for production of CI which relies on the fact that poorly conidiating cultures yielded CI activity with approximately sevenfold-higher potency than CI produced by conidiating cultures. CI from poorly conidiating cultures provided 50% inhibition of alternative pathway-mediated binding of 125I-labeled complement component C3 to cryptococcal blastoconidia at a mean concentration of 60 micrograms/ml. The ability of crude CI to inhibit the alternative complement pathway seemed to be independent of intact protein or polysaccharide structure, as evidenced by resistance of inhibitory activity to digestion by proteases, including subtilisin, alpha-chymotrypsin, papain, and pepsin as well as endoglycosidases F and H. Separation of the active inhibitory component of CI from contaminating materials contained in crude CI preparations was achieved by using Phenylsuperose hydrophobic interaction chromatography in a fast protein liquid chromatography system. The active material proved to be extremely hydrophobic, desorbing from the column only during elution with ethanol; it contained only 15% protein and 5% polysaccharide. Furthermore, results from preparative thin-layer chromatography indicated that lipids which comigrated with phosphatidylserine/phosphatidylinositol and phosphatidylethanolamine possessed significant complement-inhibitory activity. Taken together, these data suggested that phospholipids from A. fumigatus contributed to the functional activity of CI. PMID- 2228222 TI - Excystation of in vitro-derived Giardia lamblia cysts. AB - This is the first in-depth analysis of the excystation of Giardia lamblia cysts prepared in vitro. Its goals were both to achieve efficient excystation and to gain insights into this crucial but poorly understood process. To identify the critical elements of excystation, we tested the sequential low-pH induction and protease treatments which had been reported to be important for excystation of fecal cysts. The optimal pH for induction of excystation was 4.0. Emergence was greatly (approximately 10-fold) stimulated by subsequent exposure of in vitro derived cysts to chymotrypsin, trypsin, or human pancreatic fluid. The stimulatory activity of each was abolished by soybean trypsin inhibitor, demonstrating that the activity of pancreatic fluid was due to these proteases. Excystation of in vitro-derived cysts was approximately 10 to 38%. Although the walls of in vitro-derived cysts were partially digested by protease treatment, trophozoites emerged only from one pole, as observed with fecal cysts. The conditions of encystation also determined the efficiency of excystation. Specifically, encystation in the presence of lactic acid, a major metabolite of colonic bacteria, stimulated excystation approximately fourfold, although it did not increase the total numbers of cysts. These experiments have shown that excystation of in vitro-derived cysts reflects that of cysts purified from human feces in that it is dependent upon conditions which simulate the passage of cysts through the human stomach (low pH) and into the small intestine (pancreatic proteases). PMID- 2228223 TI - Role of lipopolysaccharides in adherence of Actinobacillus pleuropneumoniae to porcine tracheal rings. AB - The ability of 17 Actinobacillus pleuropneumoniae isolates, representing serotypes 1, 2, 5, and 7, to adhere to tracheal rings maintained in culture was examined. Porcine tracheal rings were infected, and 8 h after inoculation, adherent bacterial cells were evaluated. A. pleuropneumoniae adhered to tracheal rings, and marked variations were observed between and even within serotypes, suggesting that adherence of this microorganism is not primarily related to the serotype of the isolate. No relationship was found between adherence to porcine tracheal rings and plasmid profiles, virulence in mice, hemagglutination, capsular material thickness, or whole-cell protein profiles. On the other hand, we observed that all isolates of serotypes 1 and 5 had a semirough-type lipopolysaccharide (LPS), whereas isolates of serotypes 2 and 7 had a smooth-type LPS (75%) or a semirough-type LPS (25%). Results showed that 83% of isolates with a smooth-type LPS adhered in large numbers to tracheal rings, whereas 80% of isolates with a semirough-type LPS adhered poorly (P less than 0.007). Our data indicated that the degree of adherence of A. pleuropneumoniae to porcine tracheal rings appeared to be related, at least in part, to LPS profiles. Furthermore, LPS seemed to be the adhesin of A. pleuropneumoniae, since purified LPS blocked adherence of this microorganism to porcine tracheal rings. PMID- 2228226 TI - Reduced lymphocyte responses to mitogens in natural and experimental trichomoniasis. AB - Proliferative responses to mitogens were determined by using peripheral blood mononuclear cells from women with active trichomoniasis, with serological evidence of past infection with Trichomonas vaginalis, and with no evidence of current or past infection. Even after the human immunodeficiency virus antibody status of the patients was taken into account, cells from women with active trichomoniasis showed reduced responses to phytohemagglutinin, concanavalin A, pokeweed mitogen, and bacterial lipopolysaccharide. Similar findings were obtained by using spleen cells from mice inoculated subcutaneously with live trichomonads. Reduction in proliferative responses by these cells could be detected 3 days after inoculation. There was some evidence to suggest that more pathogenic strains of the parasite induced a greater degree of immunosuppression. The responses of spleen cells from mice inoculated with trichomonad-free culture supernatants were within normal limits, indicating that live trichomonads were needed to induce suppression. Support for this was gained from studies with cells from women who were treated successfully. Cells from these women rapidly regained normal lymphoproliferative function. Interleukin-2 (IL-2) production by spleen cells from infected mice was determined from measurements of mitochondrial activity in an IL-2-dependent T-cell line following incubation with stimulated spleen cell culture supernatants. These tests demonstrated lower IL-2 activity in supernatants from cell cultures from infected mice than in those from uninfected mice. The reduction in IL-2 activity did not, however, appear to correlate with the degree of reduction of mitogen-induced lymphoproliferation. Suppression of T cell-mediated immunity may be one of the mechanisms by which T. vaginalis is able to evade host responses to infection. PMID- 2228225 TI - Immunological cross-reactivity between Streptococcus mutans and human heart tissue examined by cross-immunization experiments. AB - Hyperimmunization of rabbits with Streptococcus mutans or other related cariogenic streptococci sometimes induces serum antibodies that react with human heart muscle. To determine whether antigen I/II (AgI/II), a major surface protein antigen present in most human isolates of these organisms, was responsible for inducing cross-reactive antibodies, we tested it for antigenic similarity to heart components, exploiting the ability of immune systems to mount anamnestic responses to antigens previously encountered. Mice immunized with a strain of Streptococcus pyogenes type M6, known to be heart cross-reactive, or with intact S. mutans cells developed antibodies that could be detected on a human heart sarcolemmal preparation. However, mice immunized with AgI/II and boosted with sarcolemma were unable to develop significant antisarcolemmal antibodies attributable to prior sensitization by AgI/II. Similarly, AgI/II was unable to recall antisarcolemmal responses in mice previously immunized with sarcolemma. Nevertheless, strong immunoglobulin G antibody responses to AgI/II were detected at the single-cell level in spleens and as circulating antibodies in all mice immunized with AgI/II or AgI/II-bearing S. mutans. We conclude that the ability of S. mutans to induce heart-reactive antibodies is not due to antigenic similarity between AgI/II and components of human heart but may be caused by other cross-reactive antigens in the bacterial cells or by nonspecific stimulation of the immune system. PMID- 2228224 TI - Immunoreactivity of neoglycolipids constructed from oligomannosidic residues of the Candida albicans cell wall. AB - To establish a model to study the immunoreactivity of oligosaccharidic structures from the Candida albicans cell wall, we attempted to construct neoglycolipids with these residues by using oligomannosides released after mild acid hydrolysis of the phosphopeptidomannans isolated from yeast forms. From a mixture of manno oligosaccharides ranging from mannobiose to mannononaose, the structure of a quantitatively major component (mannotriose) was determined to be Man (beta 1-2) Man (beta 1-2) Man alpha by 1H nuclear magnetic resonance analysis. After coupling of the pool of oligosaccharides to a lipid (4-hexadecylaniline), the synthesized molecules were injected into mice and rats. Antibody responses were detected on enzyme-linked immunosorbent assay plates coated with either phosphopeptidomannans or neoglycolipids. The hybrid molecules exhibited both immunogenicity and antigenicity. The kinetics of antibody responses as well as immunofluorescence patterns observed on whole C. albicans cells strongly mimicked results from the immunization of animals with natural antigens. Construction of neoglycolipids could therefore provide an interesting approach to the study of specific oligosaccharides of C. albicans and their recognition by the host immune system. PMID- 2228227 TI - Differential induction of bone marrow macrophage proliferation by mycoplasmas involves granulocyte-macrophage colony-stimulating factor. AB - We have studied the ability of three different Mycoplasma species to induce proliferation of bone marrow-derived macrophages (BMM). We observed a significant mitogenic effect when BMM cells from BALB/c, DBA/2J, SJL, and C57BL/6 mice were incubated with membranes derived from Mycoplasma arginini or M. arthritidis but not when they were incubated with an equivalent amount of M. pulmonis membrane. We also determined that pretreatment of mycoplasma membrane preparations with papain eliminated the ability of these preparations to induce BMM proliferation. To determine whether these membrane fractions acted indirectly by stimulating the production of soluble factors known to stimulate proliferation of BMM cells, we performed blocking studies with antibodies directed against colony-stimulating factor 1 (CSF-1), interleukin-3 (IL-3), and granulocyte-macrophage colony stimulating factor. Our results indicate that antibodies directed against either CSF-1 or IL-3 failed to block mycoplasma-initiated proliferation of BMM cells. However, when anti-GM-CSF was added to proliferative cultures at the time of initiation, we saw a dose-dependent reduction of mycoplasma-initiated proliferation. We conclude that the ability of mycoplasma membranes to initiate the proliferation of BMM is not shared by all species of mycoplasma and that it involves the production of GM-CSF by an as yet undetermined cell. PMID- 2228228 TI - Mycoplasmas induce transcription and production of tumor necrosis factor in a monocytic cell line, THP-1, by a protein kinase C-independent pathway. AB - We demonstrated that mycoplasmas (MP), previously shown to augment the antitumor activity of murine peritoneal macrophages, also induce cytotoxic activity in a human monocytic cell line, THP-1. THP-1 cells were induced to produce cytotoxic activity by MP in a time- and dose-dependent manner. By using neutralization by antibody against tumor necrosis factor (TNF), the cytotoxic activity was shown to be due to TNF released from the MP-stimulated cells. Studies with inhibitors of second-messenger pathways and Northern RNA blot analysis indicated that a Ca2(+) dependent, but not protein kinase C-dependent, biochemical pathway is involved in MP-induced TNF production by THP-1 cells and that MP induce TNF production in the cells at the level of transcription. MP, unlike other bacteria, lack cell walls and lipopolysaccharide. The possible involvement of a TNF production mechanism distinct from that triggered by lipopolysaccharide is discussed. PMID- 2228229 TI - Molecular epidemiologic evidence for association of thermostable direct hemolysin (TDH) and TDH-related hemolysin of Vibrio parahaemolyticus with gastroenteritis. AB - The Kanagawa phenomenon induced by the thermostable direct hemolysin (TDH) of Vibrio parahaemolyticus is almost exclusively associated with clinical strains, and TDH has been considered an important virulence factor. However, Kanagawa phenomenon-negative strains isolated from patients with diarrhea have recently been shown to produce TDH-related hemolysin (TRH). We studied the distribution of the tdh gene encoding TDH and the trh gene encoding TRH in vibrios by hybridization analyses. The presence or absence of the tdh gene and the trh gene in 285 strains of V. parahaemolyticus was examined by the DNA colony hybridization test with a tdh gene-specific probe and a newly constructed trh gene-specific probe. For assessment of the importance of TRH, many Kanagawa phenomenon-negative clinical strains (35.4% of all strains) were included. Of 214 clinical strains of V. parahaemolyticus, 112 strains (52.3%) had the tdh gene only, 52 strains (24.3%) had the trh gene only, and 24 strains (11.2%) carried both the tdh and the trh gene. The coexistence of the tdh and trh genes in these 24 strains was confirmed by Southern blot hybridization analysis. Of 71 environmental strains, 5 strains (7.0%) hybridized very weakly with the trh gene probe and none hybridized with the tdh gene probe. These results suggest that TRH as well as TDH is an important virulence factor of V. parahaemolyticus. Among 118 strains of other Vibrio species examined for the trh gene, only 1 strain of Vibrio furnissii gave a very weak hybridization signal. Among 48 representative trh gene-positive strains of V. parahaemolyticus, only 18 strains (37.5%) were found to produce TRH in culture medium when examined by a sensitive enzyme-linked immunosorbent assay method. PMID- 2228231 TI - Genetic relationships among strains of avian Escherichia coli associated with swollen-head syndrome. AB - Genetic diversity among 22 Escherichia coli strains isolated from chickens with swollen-head syndrome (SHS), an acute respiratory disease of domestic poultry, and 93 strains isolated from birds with colibacillosis was assessed on the basis of allelic variation at 20 enzyme-encoding loci detected by multilocus enzyme electrophoresis. SHS isolates from Spain and Canada were polymorphic at 14 loci and were classified into 19 multilocus genotypes, defining clones that differed on average at 34% of the loci. In most cases, SHS isolates of different clonal genotypes were distinct in O:H serotype and expressed different fimbrial antigens. Comparisons with 93 isolates obtained from birds with colibacillosis revealed enzyme polymorphisms at 17 of 20 loci, with an average of 3.5 alleles per locus. In the total sample, 56 clonal genotypes were distinguished, with 27 (23%) of the isolates belonging to one of three common clones. Both SHS and colibacillosis isolates were genetically diverse, with an average single-locus diversity of 0.36, indicating that a wide variety of naturally occurring bacterial clones is associated with these acute avian infections. Six previously defined groups of clones identified in diseased birds from the United States were represented in isolates from Spain, indicating that similar clones occur in widely separated geographic areas. In addition, one group of SHS isolates was closely related to a recognized widespread clone complex incriminated in human septicemia and meningitis. The results suggest that certain strains implicated in SHS infections belong to a clone complex whose members have special attributes that promote involvement in invasive diseases in humans and animals. PMID- 2228232 TI - Adenylate cyclase toxin of Bordetella pertussis: production, purification, and partial characterization. AB - Bordetella pertussis produces a number of virulence determinants which contribute to its pathogenicity. One factor, the adenylate cyclase toxin (ACT), has been suggested to directly penetrate human phagocytes and disrupt their normal function by direct production of intracellular cyclic AMP (cAMP). Experiments evaluating the production of cell-associated ACT in liquid cultures of B. pertussis 504 demonstrated that the greatest activity was observed during mid-log phase growth. Urea extracts of cells harvested during the time of maximal ACT production have been used to purify the toxin with both biological and enzymatic activities. ACT is a protein with an apparent molecular mass of 220 kDa and an isoelectric point of 7.0. The specific activity of purified ACT is 17,000 mumol of cAMP formed per mg per min. The the biological specific activity of purified ACT is 6,250 nmol of intracellular cAMP formed per mg per min in 2 x 10(6) S49 lymphoma cells per ml. Preparations containing 8 micrograms of ACT completely abrogated the chemiluminescence response of 2 x 10(6) human neutrophils per ml. PMID- 2228233 TI - Cytotoxic and hemolytic effects of Tritrichomonas foetus on mammalian cells. AB - Geographically distinct lines of Tritrichomonas foetus were assayed for their ability to cause cytotoxicity in nucleated mammalian cells and lysis of bovine erythrocytes. T. foetus was highly cytotoxic toward a human cervical cell line (HeLa) and early bovine lymphosarcoma (BL-3) but displayed low levels of cytotoxicity against African green monkey kidney (Vero) cells. In addition to variation in the extent of cytotoxicity toward different targets, differences in the levels of cytotoxicity in the same nucleated target occurred with different parasite lines. Whole T. foetus, unfractionated whole-cell extracts, and parasite conditioned medium (RPMI 1640 without serum) all caused lysis of bovine erythrocytes. Lytic activity in the conditioned medium was substantially reduced by repeated freezing and thawing or heating to 90 degrees C for 30 min. Damage of mammalian target cells by live T. foetus could be reduced by the presence of protease inhibitors; however, such inhibitors did not diminish the lytic effects of conditioned medium. These results suggested that proteolytic enzymes were necessary for the lytic mechanism of the live parasites but were not required once lytic factors were released into the parasite-conditioned medium. They further suggested that the lytic molecules were either proteins or had proteinaceous components. PMID- 2228234 TI - High-frequency spontaneous mutation of classical Vibrio cholerae to a nonmotile phenotype. AB - The species Vibrio cholerae contains within it two biotypes, classical and El Tor, both of which are motile. Phenotypic expression of motility was unaffected by type of growth medium, salt concentration, pH, or temperature of incubation. However, seven strains of classical V. cholerae produced spontaneous nonmotile mutants at an unusually high frequency (ca. 10(-4)), while no mutants were detected for all three El Tor strains examined. No revertants of these nonmotile mutants were detected. Four independent mutants of classical strain 395 were isolated to characterize this phenomenon. By transmission electron microscopy, one of the nonmotile mutants was found to be flagellated, while the other three were found to be aflagellate. Chromosomal DNA from the mutants and parental wild type strain 395 was examined by Southern blot analysis with, as probes, V. cholerae mutagenic prophages VcA-1 and VcA-2 and six cloned motility gene regions isolated from transposon insertion motility mutants of strains 395 and N16961 (El Tor, Inaba). The parental wild-type strain and all of the mutants exhibited the same pattern of bands when probed with VcA-1 and VcA-2 DNAs. Four of the cloned motility gene regions hybridized to the same fragments of DNA in both the wild type and mutant isolates. However, two other probes detected a new fragment for a single aflagellate mutant. The observations that spontaneous nonmotile mutants occurred at a high frequency and that these mutants did not revert at a detectable frequency suggested that a genetic event is involved. The phenomenon appears to be limited to classical V. cholerae and may explain why classical V. cholerae is only sporadically associated with disease in the current pandemic. PMID- 2228230 TI - Immunopathology of experimental Chagas' disease: binding of T cells to Trypanosoma cruzi-infected heart tissue. AB - The immunopathology of Chagas' disease was studied in the experimental model of chronic infection in C57BL/10JT or mice. Sublethal infection with Trypanosoma cruzi, Y strain, induced specific antibodies and a delayed hypersensitivity response to parasite antigens. Mice developed chronic chagasic myocarditis but not skeletal muscle myositis. Binding of T cells to infected heart tissue was investigated during short-term cocultivation of lymphocytes with heart cryostat sections. T cells from infected mice and from normal controls bound equally to myocardium and liver sections from both infected and normal mice. A search in depth was attempted with cells heavily tagged with 99mTc. Labeled T cells from chagasic mice bound to both normal and infected myocardium slices. 99mTc-labeled T cells from controls gave the same binding values. Glass-adherent spleen cells behaved identically to T cells. Prior treatment of the tissue with serum from chronically infected mice did not increase the number of binding cells. Peritoneal macrophages tagged with 99mTc-sulfur colloid also bound to infected myocardium slices. The binding of macrophages was not changed by pretreatment of infected tissue with anti-T, cruzi antibodies. In short, this work did not detect any population of T cells or macrophages which could bind specifically to infected heart tissue to initiate an autoreactive process. PMID- 2228235 TI - Chlamydicidal activity of human alveolar macrophages. AB - Pneumonia due to Chlamydia trachomatis is a disease limited mainly to infants under 6 months of age. Rare cases have been reported in immunocompromised adults. One possible reason for the propensity of the pneumonia to occur in the very young may be related to differences in the phagocytic and bactericidal capacity of alveolar macrophages (AMs) in young infants and adults. At birth a function of AMs is clearance of surfactant-related material from the alveolar surface. Studies in animals have suggested that engorgement of AMs with surfactant-related lipids may reduce the microbicidal capacity of these cells. In the present study we determined that AMs obtained from healthy, nonsmoking adults were capable of killing both human biovars of C. trachomatis, with complete killing observed by 48 h after inoculation. Preincubation of AMs from adults with surfactant did not reduce the capacity of the cells to kill C. trachomatis. PMID- 2228237 TI - Engineering of genetically detoxified pertussis toxin analogs for development of a recombinant whooping cough vaccine. AB - Pertussis toxin (PT) is an important protective antigen in vaccines against whooping cough, and a genetically detoxified PT analog is the preferred form of the immunogen. Several amino acids of the S1 subunit were identified as functionally critical residues by site-directed mutagenesis, specifically, those at positions 9, 13, 26, 35, 41, 58, and 129. Eighty-three mutated PT operons were introduced into Bordetella parapertussis, and the resultant toxin analogs were screened for expression levels, enzymatic activity, residual toxicity, and antigenicity. While more than half of the mutants were found to be poorly secreted or assembled, the rest were fully assembled and most were highly detoxified. Single mutations resulted in up to a 1,000-fold reduction in both toxic and enzymatic activities, while PT analogs with multiple mutations (Lys-9 Gly-129, Glu-58 Gly-129, and Lys-9 Glu-58 Gly-129) were 10(6)-fold detoxified. Operons coding for stable and nontoxic mutants shown to express a critical immunodominant protective epitope were returned to the chromosome of Bordetella pertussis by allelic exchange. In vivo analysis of the toxin analogs showed a dramatic reduction in histamine sensitization and lymphocytosis-promoting activities, paralleling the reduction in toxic activities. All mutants were protective in an intracerebral challenge test, and the Lys-9 Gly-129 analog was found to be significantly more immunogenic than the toxoid. PT analogs such as those described represent suitable components for the design of a recombinant whooping cough vaccine. PMID- 2228238 TI - Opsonic effect of jacalin and human immunoglobulin A on type II group B streptococci. AB - This study examined the effect of immunoglobulin A (IgA) and the IgA-binding lectin jacalin on the phagocytosis of type II group B streptococci (GBS). Strains possessing the trypsin-sensitive and trypsin-resistant components of the c protein (II/c) and type II GBS lacking the c protein (II) were examined by radiolabeled bacterial uptake, bactericidal assays, and electron microscopy. Type II/c GBS resisted phagocytosis by monocytes (4.9% +/- 0.8% uptake, mean +/- SE, n = 25) compared with type II GBS (8.5% +/- 1.4% uptake, n = 14, P = 0.03). Phagocytic killing by polymorphonuclear leukocytes was also less for the type II/c strain 78-471 than for the type II strain 79-176 (68% +/- 5% versus 86% +/- 4% reduction in CFU at 45 min, P = 0.03). IgA binding did not explain the resistance of type II/c GBS to phagocytosis. The uptake of type II/c GBS was not significantly different after opsonization in cord sera lacking endogenous IgA (5.93% +/- 1.4%) than in the same cord sera after addition of exogenous IgA (5.48% +/- 1.4%, P = 0.69, n = 9). Attempts to remove serum IgA with the IgA binding lectin jacalin resulted in the binding of IgA-jacalin complexes to II/c GBS. This combination of nonspecific IgA and jacalin increased uptake of II/c GBS from 4.9% +/- 0.8% to 11.8% +/- 1.9% (P = 0.002). Jacalin also combined with specific, immune, monoclonal IgA bound to the surface of Haemophilus influenzae and promoted the uptake of these bacteria. Jacalin and IgA mediated phagocytosis of II/c GBS via receptors that were not dependent on divalent cations and that were not modulated by plating monocytes on antigen-antibody complexes. PMID- 2228236 TI - Construction of a bifunctional Escherichia coli heat-stable enterotoxin (STb) alkaline phosphatase fusion protein. AB - A fusion between the genes encoding the Escherichia coli STb heat-stable enterotoxin (estB) and alkaline phosphatase (phoA) was constructed, and the expressed protein product was characterized. The STb-alkaline phosphatase protein (STb-PhoA) had an apparent molecular mass of 50,000 daltons and was detected with both monoclonal anti-alkaline phosphatase and polyclonal anti-STb antibodies. Expression of the gene fusion resulted in high-level production of alkaline phosphatase activity, indicating that STb-PhoA was processed and exported into the periplasm of the E. coli host strain. Amino acid sequence analysis of the hybrid protein yielded the sequence Ser-Thr-Gln-Ser-Asn-Lys-Lys, indicating that STb-PhoA was processed during export in a fashion identical to that of native STb (Y. M. Kupersztoch, K. Tachias, C. R. Moomaw, L. A. Dreyfus, R. G. Urban, C. Slaughter, and S. Whipp, J. Bacteriol. 172: 2427-2432, 1990). STb-PhoA was purified from an expressed bacterial lysate by preparative isoelectric focusing. In a rat ligated intestinal loop model, purified STb-PhoA induced highly significant (P less than 0.002) fluid secretion. In addition, the specific activity of STb-PhoA was nearly identical to that of purified STb. Thus, the STb PhoA hybrid protein represents a readily obtainable source of biologically active (STb) enterotoxin that may prove useful in studies to determine the mode of toxin action. PMID- 2228239 TI - Insertional inactivation of the gene encoding a 76-kilodalton cell surface polypeptide in Streptococcus gordonii Challis has a pleiotropic effect on cell surface composition and properties. AB - A library of Streptococcus gordonii DL1-Challis DNA was constructed in lambda gt11. Phage plaques were screened for production of antigens that reacted with antiserum to S. gordonii cell surface proteins. A recombinant phage denoted lambda gt11-cp2 was isolated that carried 1.85 kb of S. gordonii DNA and that expressed an antigen with a molecular mass of 29 kDa in Escherichia coli. Antibodies that reacted with the expression product were affinity purified and were shown to react with a single polypeptide antigen with a molecular mass of 76 kDa in S. gordonii DL1-Challis. A segment (0.85 kb) of the cloned DNA within the transcription unit was ligated into a nonreplicative plasmid carrying an erythromycin resistance determinant and transformed into S. gordonii DL1-Challis. The plasmid integrated onto the chromosome, and expression of the 76-kDa polypeptide antigen was abolished. The gene inactivation had no obvious effect on bacterial growth or on a number of phenotypic properties, including hydrophobicity and adherence. However, it abolished serum-induced cell aggregation, mutant cells had reduced aggregation titers in saliva and in colostrum immunoglobulin A, and it also reduced coaggregation with some Actinomyces species. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles of cell envelope proteins from wild-type and mutant strains showed that as well as lacking the surface-exposed 76-kDa polypeptide, mutant cell envelopes were deficient in several other polypeptides, including those that bound to immunoglobulin A. Expression of the gene encoding the 76-kDa polypeptide in S. gordonii appeared to be critical for functional conformation of the cell surface. PMID- 2228240 TI - Purification and characterization of a novel hemagglutinin from Vibrio cholerae. AB - A lectin with strong hemagglutinating activity toward erythrocytes of several animal species was isolated from an 18-h culture supernatant of a diarrheagenic strain, V2, of non-O1 Vibrio cholerae. The hemagglutinin (HA) was purified free of lipopolysaccharide by salt fractionation followed by gel filtration, hydrophobic interaction chromatography, and, finally, gel filtration in the presence of urea and deoxycholate. The purification procedure resulted in an HA preparation with 80-fold enhancement of specific activity. The HA consisted of noncovalently bound subunits of Mr 62,000 and behaved essentially as a single component with pI 6.0. Nonpolar and acidic amino acids contributed 46 and 24%, respectively, to the total amino acid residues. Electron micrographs of the HA showed it to consist of large, nonstoichiometric aggregates' of disklike molecules of 10-nm diameter. Inhibition of the HA by the glycoproteins fetuin, asialofetuin, and mucin, but not by ovalbumin and simple sugars, suggested the specific requirement of complex carbohydrates for binding. Rabbit antisera to the purified HA inhibited the hemagglutinating activities of the crude cell-free HA preparations, but not cell-associated HA activities of the parent (V2) or of other O1 and non-O1 V. cholerae strains. This suggested that the released and cell-associated HA activities were mediated by antigenically distinct components. Immunoblotting experiments showed that the antisera recognized a polypeptide component of Mr 62,000 in the cell envelope preparations of the parent and several other V. cholerae O1 and non-O1 strains. These data suggested that the HA was a nonfimbrial lectin of somatic origin with no protease activity and was apparently distinct from V. cholerae HAs described so far. PMID- 2228241 TI - Activation of cholera toxin-specific T cells in vitro. AB - Cholera toxin (CT) and its B subunit (CT-B) are potent oral immunogens in vivo, although both strongly inhibit polyclonal lymphocyte activation in vitro. In order to help understand this paradox, we have studied the activation and proliferation of CT-specific T cells in vitro, by using CT-B-primed lymph node T cells as responders, concanavalin A-stimulated peritoneal macrophages as antigen presenting cells (APCs), and various forms of CT-B as antigen. The results indicate that in many ways CT-specific T cells respond in a manner similar to that of T cells specific for other protein antigens: the degree of proliferation was proportional to the dose of antigen and APCs in the cultures, was antigen specific, and was H-2 restricted. APCs from genetic high-responder strains to CT stimulated significantly more proliferation in F1 (high x low) responder T cells than did APCs from low responder strains. However, there was a marked difference in the activation of CT-specific T cells when different forms of CT-B were used. Native CT-B stimulated little or no T-cell proliferation, whereas denatured CT-B or CT-B blocked by its ligand, GM1 ganglioside, stimulated T cells well. Addition of native CT-B to cocultures of primed T cells, APCs, and these latter stimulatory forms of CT-B inhibited the specific proliferative response to CT-B to varying degrees, depending on the ratio of the two forms in culture. We conclude that the ability of CT-B to inhibit T cells extends even to T cells specific for CT itself. Because of these inhibitory properties, processing of CT to nonbinding molecular forms or fragments must be an important prerequisite for the immune response to CT to occur in vivo, and such processing is likely to be important in the immune response to a variety of other enterotoxins as well. PMID- 2228242 TI - Enterotoxin and cytotoxin production by enteroinvasive Escherichia coli. AB - It has long been suspected that besides their ability to invade enterocytes, enteroinvasive Escherichia coli (EIEC) strains have the ability to elaborate an enterotoxin. We tested 35 EIEC strains for cytotoxins and 9 (1 per serogroup) for enterotoxins. All 35 strains exhibited low levels of Vero cell cytotoxins that are immunologically and genetically distinct from Shiga-like toxin I or II of enterohemorrhagic E. coli. Sterile supernatants and cell lysates of two EIEC strains were tested in rabbit ileal loops, and both stimulated moderate fluid accumulation (circa 0.5 ml/cm) without tissue damage; secretory activity was confirmed in Ussing chambers, where these two strains and the seven others tested significantly increased short circuit current without altering tissue conductance. Curing the 140-MDa invasiveness plasmid from an EIEC strain did not diminish enterotoxin production. Culture in minimal Fe2+ medium is necessary to detect expression of the enterotoxin which is circa 68 to 80 kDa in size and is distinct from the EIEC cytotoxin. PMID- 2228243 TI - Rapid membrane permeabilization and inhibition of vital functions of gram negative bacteria by bactenecins. AB - Bactenecins are a class of arginine-rich antibacterial peptides of bovine neutrophil granules. Two bactenecins with approximate molecular weights of 5,000 and 7,000 designated Bac5 and Bac7, respectively, exert in vitro a potent bactericidal activity toward several gram-negative bacteria (R. Gennaro, B. Skerlavaj, and D. Romeo, Infect. Immun. 57:3142-3146, 1989). We have now found that this activity shows an inverse relationship to the ionic strength of the medium and is inhibited by divalent cations and greatly potentiated by lactoferrin. Under conditions supporting marked bactericidal activity, the two peptides cause a rapid increase in the permeability of both the outer and inner membranes of Escherichia coli, as shown by unmasking of periplasmic beta lactamase and of cytoplasmic beta-galactosidase. In addition, the two bactenecins inhibit the respiration of E. coli and Klebsiella pneumoniae but not of Bac5- and Bac7-resistant Staphylococcus aureus. Furthermore, they induce a drop in ATP content in E. coli, K. pneumoniae, and Salmonella typhimurium and a marked decrease in the rates of transport and incorporation of [3H]leucine and [3H]uridine into E. coli protein and RNA, respectively. In general, all these effects become evident within 1 to 2 min and reach their maximal expression within about 5 min. Overall, these data strongly suggest that the decrease in bacterial viability is causally related to the increase in membrane permeability and the subsequent fall in respiration-linked proton motive force, with the attendant loss of cellular metabolites and macromolecular biosynthesis ability. PMID- 2228244 TI - Identification and characterization of a zinc metalloprotease associated with invasion by the fish pathogen Vibrio anguillarum. AB - An invasiveness-defective mutant of the fish-pathogenic bacterium Vibrio anguillarum was isolated. Compared with the wild type, this mutant had a 1,000 fold higher 50% lethal dose after immersion infection of rainbow trout, Oncorhynchus mykiss, while after intraperitoneal infection, the mutant had only a 10-fold higher 50% lethal dose. In addition, the mutant showed a lower level of protease activity. Two forms of the protease (Pa and Pb) were found after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of nonheated samples. Pa was found predominantly in protease preparations of the wild type, while Pb was the predominant form in the mutant. Conversion of Pb to Pa was observed in protease preparations after incubation at 4 degrees C. Characterization of the protease showed that it was an elastolytic enzyme which required Zn2+ for activity and Ca2+ for stability. The molecular mass of the protease was 36 kilodaltons. N terminal amino acid sequence analysis of the protease of V. anguillarum revealed homology to the elastase of Pseudomonas aeruginosa and the protease of Legionella pneumophila. PMID- 2228245 TI - Cytokine induction by lipopolysaccharide (LPS) corresponds to lethal toxicity and is inhibited by nontoxic Rhodobacter capsulatus LPS. AB - Many pathological effects of gram-negative bacteria are produced by their cell wall-derived lipopolysaccharides (LPSs). Differing pathogenicity of gram-negative LPSs, however, may depend on their capacities to induce cytokines. Thus, we studied the lethal toxicity of four nonenterobacterial LPSs and compared it with their capacity to induce mononuclear cell (MNC)-derived interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). Unstimulated MNC did not release these cytokines. LPS from the phototrophic strain Rhodobacter capsulatus 37b4 elaborated little toxicity in galactosamine-treated mice (10 micrograms of LPS per mouse was the 100% lethal dose [LD100]) and induced IL-1 and IL-6 release only at high concentrations (10 to 50 micrograms of LPS per ml). R. capsulatus LPS failed to induce TNF activity even at the highest concentration tested (100 micrograms of LPS per ml). In contrast, LPS derived from Pseudomonas diminuta NCTC 8545 or the nodulating species Bradyrhizobium lupini DSM 30140 and Rhizobium meliloti 10406 expressed lethal toxicity (LD100, 1,000, 100, and 10 ng per mouse, respectively) and induced IL-1 or IL-6 (10 to 100, 10, and 1 ng of LPS per ml, respectively) at concentrations 1,000- to 10,000-fold lower than effective levels of R. capsulatus LPS. LPSs from P. diminuta, B. lupini, and R. meliloti also stimulated TNF production and release. MNC accumulated cell-associated IL-1 activities under circumstances in which released activity was readily detected. The cells contained only scant IL-6 activity, indicating release of this mediator rather than intracellular accumulation. Antisera to the respective cytokines inactivated biological activities of the samples selectively. The R. capsulatus LPS inhibited cytokine induction by LPS from P. diminuta, B. lupini, and R. meliloti in coincubation experiments. These results show that the in vivo lethality of the LPSs tested correlates with the induction of monocyte-derived cytokines in vitro. The results of this study suggest that the different lethality of various LPSs from gram-negative bacteria may be due to the differential ability of these LPSs to induce cytokine production. PMID- 2228246 TI - Identification and partial characterization of a cytolytic toxin produced by Gardnerella vaginalis. AB - Generation and release into the culture medium of a cytolytic toxin by Gardnerella vaginalis has been demonstrated. Addition of starch and of the nonionic detergent Tween 80 to the culture medium was essential to recover cytolytic activity. A protein with an apparent molecular mass of 61 to 63 kDa was purified from the culture supernatants showing lytic activity towards erythrocytes and nucleated cells, such as human endothelial cells and human neutrophils. The protein had marked selectivity for human erythrocytes, while erythrocytes from other species were not lysed or were lysed at much higher concentrations of the protein than those needed for human erythrocytes. The cytolytic activity was remarkably unstable in polar media, but was stabilized by nonionic detergents, by binding, or by insertion into the target cell membrane, suggesting its amphiphilic nature. PMID- 2228248 TI - Cloning and nucleotide sequence of the gene encoding arginine deiminase of Mycoplasma arginini. AB - The existence of a mycoplasmal arginine deiminase which catalyzes the conversion of L-arginine to L-citrulline has been postulated. Here we show the partial amino acid sequence of arginine deiminase of Mycoplasma arginini and the complete nucleotide sequence of the arginine deiminase gene of M. arginini. The open reading frame deduced from this sequence consists of 1,230 bp encoding 410 amino acids. The mature form of this enzyme contains 409 amino acids after the deletion of the first methionine. In this open reading frame, TGA nonsense codons are used as tryptophan codons; this usage was verified by determination of the amino acid sequence. The molecular weight of the enzyme calculated from the deduced amino acid sequence is 46,372. Recently, the nucleotide sequence of the arginine deiminase gene of M. arginini was reported by Kondo et al. (K. Kondo, H. Sone, H. Yoshida, T. Toida, K. Kanatani, Y.-M. Hong N. Nishino, and J. Tanaka, Mol. Gen. Genet. 221:81-86, 1990). However, their sequence differed from ours in several places and especially at the C terminus. PMID- 2228247 TI - Streptococcus pyogenes clinical isolates and lipoteichoic acid. AB - Minimally subcultured clinical isolates of virulent nephritogenic and nonnephritogenic Streptococcus pyogenes of the same serotype showed major differences in lipoteichoic acid (LTA) production, secretion, and structure. These were related to changes in coccal adherence to and destruction of growing human skin cell monolayers in vitro. A possible relationship between cellular LTA content and group A streptococcal surface hydrophobicity was also investigated. Nephritogenic S. pyogenes M18 produced twice as much total (i.e., cellular and secretory) LTA as did the virulent, serologically identical, but nonnephritogenic isolate. Also, the LTAs from these organisms differed markedly. The polyglycerol phosphate chain of LTA from the nephritogenic isolate was longer (1.6 times) than was that from the nonnephritogenic isolate. Likewise, both LTAs indicated the presence of alanine and the absence of glucose. Amino sugars were found in LTA from only nephritogenic S. pyogenes. Teichoic acid, as a cellular component or secretory product, was not detected. The adherence of two different nephritogenic group A streptococcal serotypes (M18 and M2) exceeded that of the serologically identical but nonnephritogenic isolates (by about five times), indicating a correlation between virulent strains causing acute glomerulonephritis and adherence to human skin cell monolayers. Likewise, LTA from nephritogenic S. pyogenes M18 was more cytotoxic (1.5 times) than was that from the nonnephritogenic isolate for human skin cells, as determined by protein release. This difference was not perceptible by the more sensitive dye exclusion method (i.e., requiring less LTA), which emphasizes changes in host cell morphology and death. Also, the secretion of LTA by only virulent nephritogenic S. pyogenes M18 was exacerbated by penicillin (a maximum of four times). Finally, while the adherence of nephritogenic S. pyogenes M18 decreased markedly after continued subculturing in vitro, the surface hydrophobicity did not. PMID- 2228249 TI - Binding of viridans group streptococci to human platelets: a quantitative analysis. AB - The binding of viridans group streptococci with human platelets was analyzed by two-color flow cytometry. Binding was detected within 15 s of mixing bacteria and platelets. At ratios of bacteria to platelets of 1:1, 10:1, 100:1, and 1,000:1, the percentages of bound streptococci (mean +/- standard deviation) were 93.2% +/ 5.4%, 80.0% +/- 8.6%, 39.8% +/- 11.1%, and 12.5% +/- 2.0%, respectively. Binding of labeled bacteria was reversed by adding a 500-fold excess of unlabeled streptococci. These results demonstrate that streptococcus-platelet binding is rapid, reversible, and saturable, which suggests a specific receptor-ligand interaction. PMID- 2228250 TI - Fab fragments from a monoclonal antibody against a germ tube mannoprotein block the yeast-to-mycelium transition in Candida albicans. AB - Fab fragments prepared from the immunoglobulin G monoclonal antibody (MAb) 4C12, which reacts with a determinant expressed on the hyphal extension of germ tubes of Candida albicans, inhibited germ tube formation, but intact MAb 4C12 did not. Indirect immunofluorescence showed a punctate binding pattern on cells incubated with Fab fragments but a confluent binding on cells incubated with intact MAb 4C12. PMID- 2228251 TI - Resistance of congenitally immunodeficient gnotobiotic mice to vaginal candidiasis. AB - Congenitally immunodeficient beige, athymic, and beige athymic mice whose orogastric mucosal tissues were chronically colonized and infected with a pure culture of Candida albicans were found to be resistant to naturally occurring vulvovaginal candidiasis. PMID- 2228252 TI - Growth of Chlamydia trachomatis in enucleated cells. AB - Chlamydia trachomatis is an obligate intracellular parasite of eucaryotic cells. Little is known about the role of the host in supporting chlamydial replication beyond the facts that host cells provide ATP and that de novo host protein synthesis is not required for bacterial growth. To further explore potential contributions of host nuclear function to chlamydial development, we questioned whether murine C. trachomatis could grow in mouse L cells that had been enucleated with cytochalasin B. Following enucleation, cells were infected with chlamydiae and analyzed morphologically and biochemically. Late in infection, substantial numbers of chlamydiae of all developmental stages were seen within large cytoplasmic inclusions that were indistinguishable from those seen in infected intact cells. Normal numbers of infectious progeny particles were produced from enucleated cultures. We conclude that active host cell nuclear function is not required to support the growth of chlamydiae. PMID- 2228253 TI - Does asbestosis increase the risk of lung cancer? AB - The question of whether asbestos workers with or without asbestosis have the same risk of lung cancer has not been adequately addressed in the literature. Studies of asbestos workers indicate that clinical symptoms and abnormal lung X-rays are more frequent among smokers than non-smokers, and some studies show that workers with asbestosis compared to those without asbestosis are more likely to be smokers or ex-smokers. Since smoking has a large affect on the risks of lung cancer, smoking habits should be considered when evaluating the risk of lung cancer among persons with and without asbestosis. Some studies show that the risk of lung cancer is higher for persons with asbestosis compared to persons without asbestosis, but none of these studies also considered the combined effects of smoking and asbestos exposure on the risk of lung cancer. It is unlikely that the higher risk of lung cancer to persons with asbestosis is only due to their higher prevalence of smoking. Some studies have suggested that asbestos workers with asbestosis may have a higher risk of lung cancer, but no definite conclusions can be drawn since dose-response relations were not evaluated. Further studies are needed to evaluate the interrelationships of smoking, asbestosis and the risk of lung cancer. PMID- 2228254 TI - The relationship between occupational classification and low birth weight in a national sample of white married mothers. AB - The relationship between occupational classification and Low Birth Weight singletons (LBW; less than 2500 g) was studied in a sample of white married mothers employed in the National Natality Survey 1980 (N = 3300). Univariate analyses included relationship between birth weight and occupation, smoking, alcohol, parity, age, education, prenatal care, weight gain during pregnancy, gestation and sex of the singleton. Occupation was significantly associated with LBW (P less than 0.05). The LBW rate was higher among blue collar workers (162 per 1000) compared to white collar workers (132 per 1000). The mean birth weight of singletons among blue collar workers was also significantly lower compared to those among white collar workers (P less than 0.057). However, after adjusting simultaneously for the effect of the confounding variables in multiple regression analysis, occupation was no longer a significant predictor of LBW. The extent to which the validity problems may limit the interpretation of the study are discussed. PMID- 2228255 TI - Annoyance and health risk caused by military low-altitude flight noise. AB - Effects of noise of low-flying military jet aircraft were investigated from demoscopic and epidemiological points of view. Areas with different low-altitude flight noise exposure were compared with one another as to subjective annoyance, casual blood pressure and ear symptoms. With the same energy equivalent sound pressure level (Leq), the subjective disturbance caused by military low-altitude flight noise was essentially greater than that due to ordinary flight noise (in the neighbourhood of civil airports). A comparison of several areas revealed that frequencies of ear symptoms (tinnitus lasting more than one hour and permanent hearing threshold shifts of greater than 30 dB) were higher only in areas where maximal flight noise levels considerably exceeded 115 dB (A) accompanied by rapid noise level increases. Blood pressure measurements yielded significantly higher values (group difference 9 mm Hg systolic) in girls living in these highly exposed areas. Acoustic limits are proposed with respect to public health. PMID- 2228256 TI - Acute circulatory effects of military low-altitude flight noise. AB - Volunteers aged 70 to 89 years living in a senior citizen's home in Haifa were exposed to flight noise via earphones while watching video films. Their blood pressure and heart rates were measured simultaneously. A high-quality recording and reproduction technique was employed. They were exposed to the noise of two to three overflights with Lmax = 99-114 dB(A) and slow sound pressure level increase (aircraft take off) or with Lmax = 95-112 dB(A) and a fast sound pressure level increase (low-altitude flight at high subsonic speed) at intervals of 10 to 15 min. The systolic and diastolic blood pressure was raised at Lmax = 112 dB(A) and high speed level increase at the average of 23 and 13 mmHg, respectively with individual maximal values of about 40 mm Hg (systolic). In order to prevent risks to the subjects' health, the noise exposure was not raised to levels above 112 dB(A) and fast level increase, although Lmax = 125 dB(A) has been measured in 75 m-low-altitude flight areas. The blood pressure response to a repeated single exposure increased in proportion to the preceding noise exposure. At high intensities and fast level increase an up to fourfold reaction intensification was detected in the majority of subjects. This change in reactivity is regarded as the result of sensitization toward the special type of noise and the implications of these observations for the long-term effects of chronic exposure to low-altitude flight noise are considered. On the basis of these results, proposals are made for limiting values for Lmax and for the speed of sound pressure level increase, the implementation of which would lead to a marked reduction in health risks from low-altitude flight noise. PMID- 2228257 TI - Cadmium in human lung tissue. AB - In 101 unselected autopsies, cadmium (Cd) in lung tissue was analyzed by means of flameless atomic absorption spectrometry (AAS). The subjects originated from Bochum (BO), Dortmund (DO), and neighbouring cities in the Ruhr District (BO/DO) as well as from Muenster (MS) and vicinity. The sample included eight persons who had died from bronchial carcinoma. The Cd concentration in lung tissue (CdL) did not show a significant age-dependency. There was only a slight increase of CdL in the age around 50. For males, the median CdL value was found to be 1.32 micrograms/g dry wt in the age group from 20-45, 1.48 micrograms/g dry wt from 45 65, and 0.64 micrograms/g dry wt greater than 65 (the corresponding means and standard deviations were 1.48 +/- 1.22, 1.73 +/- 1.42, and 1.18 +/- 1.27 micrograms/g dry wt). CdL in men was twice that in women. There were no differences between the two regions (BO/DO:MS) examined. CdL of the bronchial carcinoma cases were mostly clearly above the expected level, often similar to the Cr and Ni concentration of the same specimens. Besides the amount of inhaled metal aerosols, insufficient lung clearance may play a leading role for their retention in lung parenchyma. However, with regard to the determination of causality between uptake and disease the data are difficult to interpret, in our study due to a lack of enough consistent and reliable data on occupation, environment, and smoking habits, and in general due to a lot of variables which, until now, cannot be sufficiently quantified. PMID- 2228258 TI - Identification of cis- and trans-verbenol in human urine after occupational exposure to terpenes. AB - Urine from sawmill workers exposed to alpha-pinene, beta-pinene and delta-3 carene was collected and hydrolyzed with beta-glucuronidase at pH 5.0 for 24 h at 37 degrees C. After hydrolysis the urine was cleaned on a SEP-PAK C18 cartridge. The cartridge was eluted with n-heptane. The eluate was injected onto a gas chromatograph equipped with a 25-m (0.32-mm ID) SP-1000 capillary column. The major peak in the chromatogram was identified by GC-MS as trans-verbenol by electron impact at 70 eV. cis-Verbenol was also identified. These metabolites could not be detected in non-hydrolyzed urine from the exposed workers or in hydrolyzed urine from an unexposed individual. The recoveries of the verbenols from hydrolyzed urine were in the range of 85 to 94% and the metabolites were stable both in urine and in n-heptane after sample cleaning at -20 degrees C for at least 12 weeks. We suggest that these metabolites are formed from alpha-pinene by hydroxylation. PMID- 2228259 TI - Biological monitoring of isocyanates and related amines. II. Test chamber exposure of humans to 1,6-hexamethylene diisocyanate (HDI). AB - Five male subjects were exposed to 1,6-hexamethylene diisocyanate (HDI) atmospheres for 7.5 h. The exposures were performed in an 8 m3 stainless steel test chamber, and the HDI atmospheres were generated by a gas-phase permeation method. HDI in air was determined by an HPLC method utilizing the 9-(N methylaminomethyl)-anthracene reagent, and by a continuous monitoring device (MDA 7100). The average air concentration was ca 25 micrograms/m3, and the inhaled dose of HDI for the different subjects was estimated at ca 100 micrograms. The related amine 1,6-hexamethylene diamine (HDA) was after acid hydrolysis of urine and plasma, determined as a heptafluorobutyric derivative, by glass capillary gas chromatography and selected ion monitoring (SIM), in a chemical ionization mode using ammonia as reagent gas. The cumulated urinary excretion of HDA during 28 h was 8.0 to 14 micrograms, which corresponds to ca 11 to 21% of the inhaled dose of HDI. The urinary level of HDA, in samples collected immediately after the end of the exposures, was on average 0.02 mmol/mol creatinine (range 0.01-0.03 mmol/mol creatinine). The urinary elimination was rapid, and half-time (t 1/2), for the concentration of HDA in urine, showed an average of 1.2 h (range 1.1-1.4 h). No specific IgE and IgG antibodies to HDI were detected before and after provocation; nor were spirometry or bronchial reactivity changed immediately and 15 h after provocation. Analysis of HDA in hydrolysed urine, as a marker of short time exposure to HDI, is proposed. PMID- 2228260 TI - Blood biochemical and cellular changes during decompression and simulated extravehicular activity. AB - Blood biochemical and cellular parameters were measured in human subjects before and after exposure to a decompression schedule involving 6 h of oxygen prebreathing. The exposure was designed to simulate extravehicular activity for 6 h (subjects performed exercise while exposed to 29.6 kPa). There were no significant differences between blood samples from subjects who were susceptible (n = 11) versus those who were resistant (n = 27) to formation of venous gas emboli. Although several statistically significant (P less than 0.05) changes in blood parameters were observed following the exposure (increases in white blood cell count, prothrombin time, and total bilirubin, and decreases in triglycerides, very-low-density lipoprotein cholesterol, and blood urea nitrogen), the changes were small in magnitude and blood factor levels remained within normal clinical ranges. Thus, the decompression schedule used in this study is not likely to result in blood changes that would pose a threat to astronauts during extravehicular activity. PMID- 2228261 TI - Modelling of environmental lead contributors to blood lead in human. AB - The Second National Health and Nutrition Examination Survey (NHANES II) is the only representative national study of body burden of lead where detailed concurrent information is available on a number of geographic and socio-economic factors. To date, however, reliable information on concurrent local environmental lead exposure for the sample has been lacking. In this study, we have identified and utilized previously unused concurrent lead exposure data. Our exposure data include time and region specific information on sales of lead from gasoline and ambient air-lead measurements from the United States Environmental Protection Agency (EPA). In addition, we have included information on lead consumed in food from the United States Food and Drug Administration (FDA). Our results indicate weak but significant associations between state sales of lead from gasoline and blood lead. In addition, we found a significant association between ambient air lead measurements and blood-lead concentrations. Socio-economic factors and life style factors were significantly related to blood lead, controlling for other possible confounders. Overall, our model explained 34% of the variance in blood lead levels, which is a significant improvement compared to the maximum of 25% from other studies using the NHANES II data. The study substantiates prior findings that the majority of the variance in overall blood lead is significantly related to lead sources other than gasoline. From a public health perspective, it is therefore imperative that lead screening programs be continued and focused on multiple sources of lead, including lead in gasoline. The study supports prior findings of a continuous decrease in blood lead, independent of decreases of lead from gasoline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228262 TI - The method of choice for the determination of 2,5-hexanedione as an indicator of occupational exposure to n-hexane. AB - To identify the method of choice for analysis of urine for 2,5-hexanedione (2,5 HD) as an indicator of occupational exposure to n-hexane, the end-of-shift urine samples of 36 n-hexane exposed male workers and 30 non-exposed male workers were analyzed for 2,5-HD under three conditions of hydrolysis, i.e. enzymic hydrolysis at pH 4.8, acid hydrolysis at pH 0.5, and without hydrolysis. The 2,5-HD concentrations thus determined were examined for correlation with 8-h, time weighted average exposure concentrations of n-hexane measured by diffusive sampling. The regression analysis showed that the 2,5-HD concentrations without any hydrolysis correlated best with the intensity of exposure to n-hexane. No 2,5 HD was detected in the urine of the non-exposed subjects under the analytical conditions with no hydrolysis. Thus, the analysis without hydrolysis was considered to be the method of choice from the viewpoint of simplicity in analytical procedures, sensitive separation of the exposed from the non-exposed, and quantitative increase in the amount of 2,5-HD after n-hexane exposure. PMID- 2228263 TI - Biological monitoring of occupational exposure to isopropyl alcohol vapor by urinalysis for acetone. AB - The relationship of the intensity of occupational vapor exposure to isopropyl alcohol (IPA) with urinary excretion of acetone and unmetabolized IPA was studied in 99 printers of both sexes, who were exposed to up to 66 ppm IPA (as time weighted average), together with toluene, xylenes, methyl ethyl ketone and/or ethyl acetate. Acetone and IPA concentrations in urine were studied also in 34 non-exposed subjects. Acetone was detectable in the urine of most of the non exposed, and the urinary acetone concentration increased in proportion to the IPA exposure intensity (r = 0.84 for observed, non-corrected values), whereas the correction for creatinine concentration or specific gravity of urine did not give a larger correlation coefficient. IPA itself was not found in the urine of the non-exposed, and was detectable in urine of only those who were exposed to IPA above a certain level, e.g. 5 ppm. The present study results suggest that urinary acetone is a valuable index for biological monitoring of occupational exposure to IPA as low as 70 ppm. PMID- 2228264 TI - Preventive restorative dentistry. AB - Greater use of conservative tooth restorations is advocated to encourage optimum tooth strength and restoration longevity. Improvements in tooth preparation instruments, and restorative materials, accompanied by use of magnification and meticulous care, afford optimum patient care for minimally sized carious lesions. PMID- 2228265 TI - Edentulism and preventive goals in the treatment of mutilated dentition. AB - The percentage of edentulous people is expected to decrease in the coming decades as a result of improved oral health, whereas the number of edentulous people will increase as a result of the strong increase in the ageing population. If the preservation of the natural dentition is no longer possible, the remaining teeth of a multilated dentition have to be extracted according to specific principles. Within the framework of the so-called 'preventive-prosthetic-treatment strategy', preservation of the alveolar ridge is the main goal. PMID- 2228266 TI - Restoring the ageing dentition: repair or replacement? AB - An old tooth does not exist on its own; therefore, any decision about a tooth demands knowledge about the elderly patient to whom the tooth belongs. If it is available, one can then evaluate the oral cavity in which the tooth resides. When all this information has been gathered, decisions about the individual tooth can be made. This paper discusses three specific issues: when does one 'patch' an amalgam restoration; when should one crown this restored tooth; and when does one 'patch' the crown, and when does one replace it? A review of the literature indicated that reliable and generally applicable data on these issues do not exist, so that these decisions are still made by clinical judgement based upon experience. In view of the known changes in caries rates, fluoridation of water supplies, and patient attitudes, dentists' judgements of appropriate restorative treatment for older adults based upon past experience may be inappropriate. Longitudinal clinical research is required to develop clinically usable guidelines, especially for the elderly. PMID- 2228267 TI - Root lesions. AB - In the elderly, but increasingly also in middle-aged patients, root lesions are a major problem in everyday practice. Formerly, the cause of these root destructions was usually caries attack due to a failure of patients to practise adequate oral hygiene measures. However, with increasing dental motivation and health consciousness, patients--for example in the USA, Scandinavian countries and Switzerland--cause such lesions by vigorous, badly controlled brushing, often in combination with the consumption of 'healthy' vegetarian, erosive diets. The former problem of carious root destruction due to neglect thus seems to be gradually being replaced by the problem that self-care is not yet thoroughly understood, is exaggerated and is technically inadequate. Faulty brushing may result in severe damage to those gingival sites that require attention cariologically as well as periodontologically. To exploit all possibilities of (secondary) preventive management of patients, careful investigation and analysis of the clinical signs is required to identify the aetiology of the lesions in each case. Fortunately, therapeutic management of root lesions, regardless of their aetiology, is facilitated by modern restorative techniques and materials. PMID- 2228268 TI - Palladium alloys in prosthodontics: selected aspects. AB - The high costs of gold and platinum have caused other alloys to be considered in the construction of prosthetic appliances. This paper reports on the grain structure, corrosion resistance and microstructure of palladium alloys. Also discussed are the properties of these alloys and how these affect their technical manipulation. PMID- 2228269 TI - Mandibular atrophy and metabolic bone loss. AB - Radiological studies were performed on edentulous patients with and without atrophy of the mandible. Radiological, histomorphometrical and endocrinological studies were performed in edentulous patients with a severe atrophy of the mandible treated by ridge augmentation. The results of these studies showed that metabolic bone loss, histologically and endocrinologically characterized as a secondary hyperfunction of the parathyroid glands, is a causal factor in the pathogenesis of mandibular atrophy. PMID- 2228271 TI - Politics, education and curriculum. PMID- 2228270 TI - Correlation between caries prevalence (DMFS) and periodontal condition (CPITN) in more than 2000 patients. AB - The CPITN (Community Periodontal Index of Treatment Needs) and DMFS (Decayed Missing-Filled Surfaces) index were evaluated simultaneously to provide information on the mutual influences of periodontal disease and caries. With the aid of an electronic database system the data of the caries index and periodontal index of more than 2000 patients aged between 18 and 80 years were stored and calculated. As expected, the CPITN and DMFS values increased with age. When the CPITN was selected as a reference the DMFS was found to change with increasing CPITN. With the examination method used in this study no correlation could be established between the prevalence of caries and periodontal condition, although both conditions have a common aetiological factor: microbial plaque. PMID- 2228272 TI - Transfusion risks. AB - Hepatitis remains the most serious transfusion risk, in terms of incidence and severity. Transfusion-associated AIDS, hemolytic reactions, TRALI, and anaphylaxis are severe problems that occur relatively rarely, while febrile reactions and mild allergic reactions are common but not serious. The key to avoiding all these complications is autotransfusion (see the article "Autologous Transfusion" in this issue). Although intraoperative scavenging became available in many centers in the United States in the 1980s, it is hoped that pre-deposit autotransfusion will also become widely utilized in the next decade. PMID- 2228273 TI - Autologous transfusion. AB - Autologous transfusion is but one component of the comprehensive blood conservation program. It is often appropriate to employ more than one method of autologous transfusion. In addition, use of pharmacological measures to decrease blood loss, meticulous attention to surgical hemostasis, acceptance of lower hemoglobin levels during the perioperative period, and seeking the advice of transfusion medicine experts in assessing the need for administration of blood components are also important. Finally, the risks of homologous blood transfusion should not overshadow the life-saving benefits of transfusion. PMID- 2228274 TI - Safe limits of isovolemic hemodilution and recommendations for erythrocyte transfusion. PMID- 2228275 TI - The role of colloids in blood conservation. PMID- 2228276 TI - Perioperative considerations in Jehovah's Witnesses. PMID- 2228277 TI - Optimal use of blood components. PMID- 2228278 TI - Induced hypotension. PMID- 2228279 TI - Desmopressin and antifibrinolytics. AB - Desmopressin appears to be a safe and effective hemostatic agent for use during surgery in patients with mild to moderate hemophilia or von Willebrand disease. Uremic patients also benefit from substitution of desmopressin for cryoprecipitate to control bleeding. The highly variable response to desmopressin by individual patients with hemophilia or von Willebrand disease dictates that each patient receive a trial administration prior to surgery; surgery should proceed only following verification of a therapeutically effective increase in Factor VIII and vWF after desmopressin. Use of desmopressin in patients with normal baseline hemostatic function is not clearly advantageous, although certain patient subgroups might benefit, and prospective studies have documented the drug's safety in these cases. Data are lacking to clarify a role for desmopressin during surgery in patients taking aspirin. Antifibrinolytic therapy appears to decrease bleeding without increased risk after cardiac surgery. In addition, specific use after urological surgery may be beneficial in the absence of upper urinary tract bleeding. In the last ten years, other applications for antifibrinolytic therapy have been found--both surgical (intracranial aneurysms, oral and lacrimal surgery) and nonsurgical (in cancer patients and for gastrointestinal bleeding). Although anecdotal reports have fueled fears of increased thrombosis with antifibrinolytics, controlled studies indicate no increased risk. PMID- 2228281 TI - Electromyography of rapid forearm flexion and extension and aging. AB - This investigation examined several parameters of agonist- and antagonist-muscle activity and movement time in young and old males during rapid, forearm flexion and extension tasks. Maximal isometric strength of the forearm flexors and extensors and limb-volume measurements were also procured. The subject sample included sixteen males in each of the following groups: 1) thirty to forty year olds, 2) fifty to sixty year olds, and 3) sixty-one to seventy year olds. The averaged, electromyographic patterns (AEMG) of the biceps brachii and triceps brachii muscles were recorded during unloaded and loaded trials of forearm flexion and extension to a predetermined target. Sixteen temporal and ten quantitative parameters were examined. Significant differences between age groups were observed for only the quantitative-parameter accuracy. The conclusions were that an individual's agonist- and antagonist-muscle-activity parameters are maintained into the seventh decade. Flexion and extension strengths decrease progressively with age. Analysis of the limb-volume measures revealed that the oldest group had the greatest amount of fat in each of the segments evaluated. PMID- 2228280 TI - A comparative acoustic analysis of the Laugh responses of 20- and 70-year-old males. AB - Several studies have documented age-related changes in speech or voice characteristics, but no study has reported differences across age groups in human laughter. The purpose of this investigation was to identify, describe, and compare the measurements of five acoustic correlates of elicited, spontaneous laughter in twenty- and seventy-year-old males. Five acoustic characteristics of laugh responses including Initial Laugh Fundamental Frequency (ILFo), Mean Laugh Fundamental Frequency (MLFo), Peak Laugh Fundamental Frequency (PLFo), Duration Laugh Response (DLR), and Laugh Bursts (LB) as well as Speech Fundamental Frequency (SFF) were analyzed across groups. Statistically significant differences were found between twenty- and seventy-year-old males in ILFo, MLFo, PLFo, and in the number of laughs per minute. Older respondents produced a relatively compressed fundamental frequency range of laugh behavior and fewer laugh responses per minute. These differences are congruent with age-related changes in speech and voice but also might be explained by other physiological or sociological variables. PMID- 2228282 TI - Hobbies of retired people in the People's Republic of China: a preliminary study. AB - This study describes and analyzes the hobbies of over 500 retired individuals (ages fifty to eighty-eight in the People's Republic of China. Data were obtained through questionnaires and compared with the responses of 100 younger people (twenty to thirty-nine years of age). Hobbies of the retired people were classified into five categories: reading, physical exercise, productive, visual auditory, and recreational. This classification is at variance with the one proposed by some Western writers. The following conclusions were reached: 1) there are significant differences between the hobbies of retired people and those of younger people; 2) reading is the hobby most preferred by the retired person in China; and 3) gender, age, education, and previous occupation are the factors that most influence the retired person's choice of hobbies. PMID- 2228283 TI - Leisure activities of retired persons in the United States: comparisons with retired persons in the People's Republic of China. AB - This study was undertaken in view of the large and growing numbers of retired persons in the People's Republic of China; the dearth of information about how they spend their time; and the importance of such knowledge in guiding city reform and accomplishing the Four Modernizations and the future cause. The discretionary-activity patterns and rates, the importance of these activities, and their perceived impact upon the health of 551 retired persons and 100 employed workers in Shanghai were compared in order to investigate the role of retirement in China. To assess similarities and differences between retired persons in China and in the West, the activity patterns and rates of retired Chinese adults were compared with retired adults in two samples from the United States (352 from San Antonio and 899 from San Francisco). PMID- 2228284 TI - Attitudes toward retirement in an Israeli cohort. AB - The three-fold purpose of this study was 1) to clarify the concept of "attitudes toward retirement" and its multidimensional structure; 2) to test hypotheses about the relationship between attitudes and gender and SES; and 3) to analyze the relationship between attitudes and the Sense of Coherence concept in terms of the functional consequences of different attitudes. A sample of 805 (432 men and 373 women) Israeli "on-time" people on the verge of retirement were interviewed. Results point to the importance of distinguishing between perceptions of gains and losses in the retirement developmental transition; identification of blue collar workers, with ambivalent attitudes, as a high-risk group; and the importance of a strong Sense of Coherence in adopting attitudes presumably functional in coping with the developmental transition. PMID- 2228285 TI - Gonadotropin secretion in chronic renal failure. PMID- 2228286 TI - End stage renal disease in diabetes. PMID- 2228287 TI - Materials or biomaterials? PMID- 2228288 TI - Reflection on EPO. PMID- 2228289 TI - On the need for erythropoietin treatment in dialysis patients. A Copenhagen City Dialysis Unit study. AB - We evaluated the need for erythropoietin (EPO) treatment in 134 end-stage renal disease patients assuming a level of hemoglobin below 6 mmol/l (9.6 g/dl) as indication for treatment. 91 patients (68%) fulfilled this criterion. Absolute contraindications in 2 patients were previous thrombotic encephalopathy and refusal of treatment. Relative contraindications due to cardiac disease were found in 3 patients. In 15 patients additional treatment was required because of hypertension (5) or deficiency states (10). The implications of elevated serum PTH and aluminum overload are discussed. PMID- 2228290 TI - Magnetic resonance imaging of the bone marrow following treatment with recombinant human erythropoietin in patients with end-stage renal disease. AB - We used magnetic resonance imaging (MRI) to study vertebral bone marrow in hemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). We found changes in T1 relaxation times and image contrast within 14 days after starting treatment, before any response was seen in the hemoglobin concentration in peripheral blood. The increase in T1 relaxation times, together with earlier reported changes observed with localized magnetic resonance spectroscopy, indicate an alteration in cellular composition of the hemopoietic bone marrow with an increase in the amount of hemopoietic active tissue. MRI may be a useful, non-invasive way of evaluating bone marrow response to different modes of rHuEPO administration and dosage. PMID- 2228291 TI - Hemodialysis-associated febrile episodes: surveillance before and after major alteration in the water treatment system. AB - Surveillance for bacteremic or pyrogenic episodes associated with hemodialysis was undertaken before and after the reconstruction of the water treatment system at our University medical center. The new water system included a holding tank with iodination treatment. The water delivered to individual dialysis stations had only occasional positive bacterial cultures (3 of 21 samples before completion of construction, 2 of 16 samples afterwards) and intermittent detection of endotoxin (6 of 21 samples before completion of construction, 9 of 16 samples afterwards) at monthly sampling. Among 51 individual dialysis treatments (25 patients) before reconstruction and 56 treatments (29 patients), after, only 2 and 3 febrile events were identified, respectively. All of these were associated with underlying infectious illness and not with the hemodialysis procedure itself. Overall, we conclude that pyrogenic episodes associated directly with hemodialysis treatment are infrequent, and that the addition of a water storage tank with iodination treatment does not appear to increase the risk of bacteremia or pyrogenic episodes. PMID- 2228292 TI - Mineralization of polyurethane membranes in the total artificial heart (TAH): a retrospective study from long-term animal experiments. AB - The degree of mineralization of TAH membranes in animals is directly related to the survival time of animals with a TAH. Large differences in mineralization of the membranes among individual animals have been observed. These differences can be explained by the simultaneous presence of infection on biomaterials (polyurethane) as well as by different levels of natural inhibitors of mineralization. No positive influence of applying sodium warfarin for the inhibition of the mineralization was observed. PMID- 2228293 TI - Development of a new inflow valve for a 20cc semisoft ventricle: preliminary results. AB - We remodeled and tested our semisoft 20cc ventricle and made a new bileaflet flap inflow valve. Housings, bases, outflow valve, and a newly designed diaphragm were all made by vacuum forming and put together by radiofrequency welding or glue. In vitro, the ventricle produced a cardiac output of 2.5 to 3.0 L/min and showed reliable durability results. Hematological testing showed no important thrombogenicity of the new valve. Cardiac output was higher than expected for the volume of the ventricle, perhaps because of stretching or flow through. Animal experiments with the left ventricular assist device (LVAD) version was done at Ohio State University. Earlier in Utah, we did 20 cc total artificial heart (TAH) implantations and LVAD experiments in lambs and recently in calves with the 60cc TAH version. A soft ventricle is easy to implant and low in production costs. PMID- 2228294 TI - In vivo effects of stroma-free hemoglobin and polyhemoglobin on coagulation factors in rats. AB - We studied the effects of rat stroma-free hemoglobin (rSFH), human stroma-free hemoglobin (hSFH), rat polyhemoglobin (rPoly), and human polyhemoglobin (hPoly) on coagulation factors in rats. Albumin and saline infused rats were controls. The infusion volume was 10% of the rat's blood volume. The concentrations of hemoglobin in this study were 7 g/dl. Measurements for prothrombin time (PT) and activated partial thromboplastin time (PTT) were at 5 minutes, 2, 6, 24 and 72 hours after infusion. Factor X, fibrinogen, plasminogen, antithrombin III, and antiplasmin were followed at 24 and 72 hours after infusion. Compared with saline infused rats PT and PTT did not change significantly in those rats infused with Hb preparations. There was a transient increase of PTT from 2 to 24 hours after infusion in albumin infused rats. Factor X, fibrinogen, antithrombin III and antiplasmin showed no significant differences between Hb infused groups and saline infused group. Twenty-four hours and 72 hours after infusion plasminogen decreased in all groups except the albumin infused rats at 24 hours after infusion when compared with normal rat plasma pool. However, there were no significant differences in plasminogen levels between the hemoglobin infused groups and the control saline group. Stroma-free and polyHb solutions (rSFH, hSFH, rPoly and hPoly) did not cause significant changes in prothrombin time and activated partial thromboplastin time in rats. The rats infused with hemoglobin solutions (rSFH, hSFH, rPoly, and hPoly) did not show significant differences in Factor X, fibrinogen, antithrombin III and antiplasmin levels compared with the control group. PMID- 2228295 TI - New approaches for biocompatibility testing using cell culture. AB - We are proposing two modified assays for biocompatibility testing which analyze the effects of cytotoxic substances leached from a biomaterial in cell culture. The biocompatibility of two vascular prostheses made of polytetrafluoroethylene was analyzed using the modified assays. One test, the "fluid medium assay" was modified by using small pieces of graft glued to a screening lid, thereby reducing the possibility of mechanical injury to cultured cells by free fragments of the tested biomaterial. Another test, the "cell inhibition assay" was modified in that the biomaterial to be tested was ground into small pieces while at very low temperature. The measure of cell toxicity used was the effect on DNA replication. Our results suggest that these modified assay methods can be used to evaluate the biocompatibility of biomaterials. PMID- 2228296 TI - Connectology problems with swan neck peritoneal dialysis catheters. PMID- 2228297 TI - Spectral resolution of cardio-circulatory variations in men measured by autorhythmometry over 2 years. AB - An analogue of the periodogram method for unequally spaced data is presented with a view to resolving the frequency structure of the observations. The algorithm is explicitly based on the sequential least squares procedure. In particular, the key concept is that the within-plot spectral analysis can be augmented by the between-plot information to make inferences about common characteristics. It is also shown how the between-plot random variations can be incorporated into the multiple harmonic regression model. A detailed spectral analysis investigates the periodic fluctuations in four cardio-circulatory variables, measured by autorhythmometric observation by eight men at rest and extending over a time span of 2 years. The spectral curves show the existence of circadian and circaseptan rhythmicities. The amplitude modulation of the dian rhythm by circaseptan variation is assimilated with the rhythmicity of work during the week. The blood pressure variables situate their maximum annual peak in the winter period. These quasi-periodic fluctuations appear to be related to the amount of physical activity performed in time by the subjects. PMID- 2228299 TI - Forecasting spore concentrations: a time series approach. AB - Fungal basidiospores and Cladosporium spores are the two most numerous spore types in the air of Dublin and its surroundings. They are known to have allergenic components, and the aim of the study described here is to develop a predictive model for these spores. A very simple model, which combines an estimated diurnal rhythm with a simple, one-parameter time series model, provided good short-term forecasts. The one-step prediction error variance was reduced by 88% for Cladosporium spores and by 98% for basidiospores. PMID- 2228298 TI - Rheological modelling of physiological variables during temperature variations at rest. AB - The evolution with time of cardio-respiratory variables, blood pressure and body temperature has been studied on six males, resting in semi-nude conditions during short (30 min) cold stress exposure (0 degree C) and during passive recovery (60 min) at 20 degrees C. Passive cold exposure does not induce a change in HR but increases VO2, VCO2, Ve and core temperature Tre, whereas peripheral temperature is significantly lowered. The kinetic evolution of the studied variables was investigated using a Kelvin-Voigt rheological model. The results suggest that the human body, and by extension the measured physiological variables of its functioning, does not react as a perfect viscoelastic system. Cold exposure induces a more rapid adaptation for heart rate, blood pressure and skin temperatures than that observed during the rewarming period (20 degrees C), whereas respiratory adjustments show an opposite evolution. During the cooling period of the experiment the adaptative mechanisms, taking effect to preserve core homeothermy and to obtain a higher oxygen supply, increase the energy loss of the body. PMID- 2228300 TI - Studies on organ weights in naproxen treated rats after intermittent exposure to simulated high altitude. AB - Rats were exposed intermittently for 8 h per day over 6 days at simulated high altitude of 20,000 feet. One group of altitude-exposed animals was treated with naproxen, a prostaglandin inhibiting drug. Significant reduction in body weight gain was observed in both altitude-exposed and drug-treated altitude-exposed animals compared to the control group. Right and left ventricular weights and weights of the adrenal glands were increased significantly in altitude-exposed and altitude-exposed drug-treated animals. The weight of the spleen was increased significantly in altitude-exposed animals whereas no such increase of splenic weight was observed in drug-treated altitude-exposed group of animals. On the other hand, the weight of the liver was decreased significantly in both cases. In drug-treated altitude-exposed animals, the unaltered splenic weight was thought to be due to inhibition of the erythropoietic activity. PMID- 2228301 TI - Body fluid status on induction, reinduction and prolonged stay at high altitude of human volunteers. AB - Studies on adaptation to high altitude (HA) of 3500 m in the Himalayas were conducted in three phases, each including 10 normal and healthy males normally resident at sea-level. Phase I subjects had no previous experience of HA, phase II subjects after 4-6 months at HA were airlifted to sea-level and phase III subjects stayed continuously for 6 months at 3500 m. Body fluid compartments and blood gases were determined in all three groups. Plasma volume was highly elevated in the phase II subjects on reinduction to sea-level from HA. In comparison to phase I subjects, the retention of fluid in extracellular compartment was increased at HA leading to increased susceptibility to high altitude illness. Phase III subjects were hyperhydrated with decreased plasma volume and increased PO2 in comparison to the other two groups. PMID- 2228302 TI - Too hot for comfort: the heatwaves in Greece in 1987 and 1988. AB - The heatwaves that affected Greece in July 1987 and July 1988 are considered in terms of (i) the relative strain index. For different types of activity, and (ii) the discomfort index. Hourly values of air temperature and humidity for Thessaloniki and Athens were used as the data base. Both indices show that in terms of physiological strain and general discomfort, Thessaloniki suffered a little more and a little longer than Athens. We conclude that the relative strain index is probably a useful tool in studies of the adverse effects of humid heatwaves on different sections of a population. PMID- 2228303 TI - Report on a Workshop of the UICC Project on Evaluation of Screening for Cancer. PMID- 2228304 TI - Total energy intake and nutrient composition: dietary recommendations for epidemiologists. PMID- 2228305 TI - Dietary factors and breast-cancer risk in Denmark. AB - The influence of dietary factors, in particular the intake of fat and beta carotene, on breast-cancer risk was evaluated in a case-control study including 1,486 breast cancer cases diagnosed over a 1 year period in Denmark. The control group was an age-stratified random sample of 1,336 women from the general population. Data on usual diet prior to the breast cancer diagnosis were collected by self-administered questionnaires of the semi-quantitative food frequency type. A highly significant trend (p less than 0.001) of increasing risk was observed with increasing fat intake, the RR for the highest quartile being 1.45 (95% Cl 1.17-1.80) compared with the lowest. However, information was not available to allow adjustment for the possible confounding effect of energy intake. The risk of breast cancer was not associated with consumption of vegetables rich in beta-carotene, multi-vitamin tablets or other dietary supplements, coffee, tea, sugar or artificial sweeteners. PMID- 2228306 TI - Humoral modulation of lymphokine-activated killer (LAK)-cell induction in humans: IgG-related and non-IgG inhibitors in sera from cancer patients. AB - Soluble inhibitors of lymphokine-activated killer (LAK) cell induction were characterized and purified from serous fluids from healthy donors or from patients with advanced cancer. Inhibitory activity in sera from cancer patients was partially absorbed with protein A agarose or anti-human IgG agarose. Following absorption, residual inhibition varied with individual sera, suggesting the presence of IgG-related and non-IgG inhibitory factors, and the proportions varied in the patient population. IgG, purified by affinity chromatography from ascitic fluids, from plasma of cancer patients, and from plasma of healthy donors, significantly inhibited IL-2 induction of LAK cells in a dose-dependent manner. Irrespective of the sources, inhibitory activity resided in the high molecular-weight IgG fraction composed of IgG aggregates and immune complexes, but not monomeric IgG. Commercially prepared human IgG in aggregated form, but not in monomeric form, inhibited LAK cell induction in a dose-dependent manner. In contrast, neither bovine IgG nor human albumin affected LAK cell induction, even at higher concentrations. Aggregated human IgG inhibited LAK cell induction in unfractionated peripheral blood mononuclear cells (PBMC) but not in monocyte depleted peripheral blood lymphocytes (PBL). Despite extensive (greater than 99%) depletion of IgG by protein-G affinity chromatography, the serous fluid from cancer patients displayed significant inhibitory activity. Fractionation of the IgG-depleted inhibitory materials by Sephacryl S-300, high-pressure ion-exchange column (HPIEC) or gel-permeation chromatography (HPGPC) demonstrated a 65-kDa inhibitor, distinct from IgG. Affigel-blue affinity chromatography of the 65-kDa fraction depleted albumin but did not remove the inhibitory activity, suggesting that the 65-kDa inhibitor is not serum albumin nor an albumin-bound component. These results suggest that serous fluids from patients with advanced-stage cancer contain 2 distinct regulators for LAK cell induction: (I) aggregated IgG and (2) a 65-kDa inhibitor, distinct from albumin. PMID- 2228307 TI - Occurrence of non-gastric cancer in the digestive tract after remote partial gastrectomy: analysis of an Amsterdam cohort. AB - If peptic ulcer surgery favors the formation of carcinogenic N-nitroso compounds in the gastric remnant, an increased risk of cancer at sites in the gastrointestinal tract distant from the stomach might be predicted. To estimate the risk of carcinomas in the digestive tract, other than the stomach, occurring after partial gastrectomy, we analyzed an Amsterdam cohort of 2,633 post gastrectomy patients operated on for benign disease between 1931 and 1960. Mortality in the study population was compared with the general Dutch population through person-year analysis. An excess mortality of biliary tract cancer (O/E:2.64; CL:1.32-4.72; p less than 0.01) and pancreatic cancer (O/E:1.65; CL:1.06-2.44; p less than 0.05) was found in males more than 5 years after surgery; females showed only an increased risk of pancreatic cancer in the first 5 years postoperatively (O/E:15.33; CL:1.85-55.43; p less than 0.01), probably due to misdiagnosis. All other non-gastric sites of the digestive tract carried no increased risk for cancer. In males, mortality due to colorectal cancer more than 5 years post-operatively was significantly decreased (O/E:0.58; CL 0.34 0.92; p less than 0.01). The excess mortality of biliary-tract and pancreatic cancer in males, which increases with the duration of post-operative interval, is consistent with a dose-response phenomenon. This study therefore supports the hypothesis that carcinogens are not only locally activated in the gastric remnant, but are hepatically excreted and initiate cancer in the biliary tree and pancreatic duct. Further exploration of this mechanism of carcinogenesis is warranted, since it may also explain the pathogenesis of pancreatic and biliary cancers in patients without gastrectomy. PMID- 2228308 TI - Age at menarche, age at menopause, height and obesity as risk factors for breast cancer: associations and interactions in an international case-control study. AB - The importance of age at menarche, age at menopause, height, and obesity as risk factors for breast cancer, and the possible interactions among these factors in breast cancer causation were investigated in a data set collected in the late 1960's, in an international multicenter case-control study. Multiple logistic regression procedures were used to model data from 3,993 breast cancer cases and 11,783 controls from 7 study centers representing the range of international variation of breast cancer incidence. Height and obesity (measured through the weight/height2 index) were independent risk factors for breast cancer among post menopausal but not pre-menopausal women; post-menopausal women taller by 10 cm had a 12% higher risk of breast cancer (95% confidence interval, CI, 3-21%) and post-menopausal women of average height (say 158 cm) had an 11% higher risk of breast cancer (CI 7-16%) when they were heavier by 10 kg (and, therefore, more obese by 4 kg/m2). Age at menarche was a risk factor among both pre-menopausal and post-menopausal women, a delay of 2 years corresponding to a 10% reduction in breast cancer risk (CI 6-15%). Age at menopause was also a breast cancer risk factor, women with menopause at each 5 year age difference having a 17% higher risk of breast cancer (CI 11-22%). There is evidence of an interaction (deviation from the logistic regression-postulated multiplicativity) between obesity and age at menarche, implying that the protective effect of late menarche may not apply to overweight women or that late menarche may become detrimental in obese women. The estimated relative risk coefficients, when applied to average risk factor levels observed among control women, can explain only a small fraction of the difference in breast cancer incidence between Boston and Tokyo. PMID- 2228309 TI - Chromosome aberrations induced by etoposide (VP-16) are not random. AB - The clastogenic effect of etoposide, an anti-cancer chemotherapeutic drug, was investigated in vitro on lymphocytes of 5 healthy donors. The analysis of the first division metaphases arising after mutagenesis in G1 phase shows that chromosome-type aberrations are much more frequent than chromatid-type lesions. The distribution in relation to chromosome lengths of the 439 breakpoints that were accurately identified is not random: chromosomes 1, 11 and 17 are most frequently involved, while chromosomes 4, 5 and X are seldom affected. This non random distribution may be related to chromosome structure, since R-band-rich chromosomes are significantly more affected than G-band-rich chromosomes. PMID- 2228311 TI - Survival of breast-cancer patients and body size indicators. AB - The association of breast-cancer survival with various risk factors was investigated using data of 213 breast-cancer patients who underwent surgical operation between 1975 and 1978. They were followed-up until 1987, and a total of 64 deaths including 47 breast-cancer deaths were certified. The 5-year and 10 year relative survival rates were 78.5% and 75.3% respectively. Of the various factors investigated, some anthropometric indicators revealed interesting results; i.e., body weight, Quetelet index, and body surface area at the time of operation turned out to be strong predictors of survival with a statistically significant trend towards lower survival with larger body structure even after adjustment for confounding factors (e.g., clinical stage) using a proportional hazard model. The estimated survival probability for women with Quetelet index of 20 was about 12% higher than that with Quetelet index of 24 over a 10-year or more follow-up period. Other variables exhibiting prognostic importance were clinical stage, TNM classification, and some histological findings, while height and reproductive life indicators were, as a rule, not significantly related to survival. PMID- 2228310 TI - Expression of HLA-A,B,C, beta 2-microglobulin (beta 2m), HLA-DR, -DP, -DQ and of HLA-D-associated invariant chain (Ii) in soft-tissue tumors. AB - Non-neoplastic mesenchymal cells, along with 33 benign and 87 malignant soft tissue tumors (STT) were examined for expression of HLA-A,B,C, beta 2 microglobulin (beta 2m), HLA-DR, -DP, and -DQ molecules and the HLA-D associated invariant chain (Ii). Serial frozen sections were immunostained using monoclonal antibodies (MAbs) to monomorphic framework determinants of HLA sublocus products, beta 2m and Ii, and to CD53, a recently defined broadly distributed pan-leucocyte molecule. Compared with the normal state, an induction/neo-expression of HLA A,B,C/beta 2m was found in a considerable number of tumors of muscle, peripheral nerve, cartilage-forming, adipose, and vascular tissues. Conversely, some tumors of fibrous origin and of autonomic ganglia showed an abnormal abrogation/loss of HLA-A,B,C/beta 2m with respect to their cells of origin. Small, round tumor cells present in various types of STT exhibited a heterogenous pattern of expression of these molecules with a preponderance of HLA-A, B,C/beta 2m-negativity. HLA-D/Ii determinants were rarely detectable in STT. Besides their expression in some fibrohistiocytic tumors, they were only occasionally found in tumors of smooth muscle, peripheral-nerve and vascular origin as well as in one clear-cell sarcoma. In all tumors but one, there was no microtopographic association between HLA-D/Ii-positive tumor cells and inflammatory cells. CD53 allowed discrimination between dendritic interstitial cells (DIC) and neoplastic cells and additionally revealed that, in contrast to other solid tumors, STT are generally characterized by an extreme scarcity of lymphohistiocytic infiltrates. Our data indicate that, aside from very rare exceptions, aberrant induction or abrogation of MHC molecules in STT occurs in the absence of lymphohistiocytic stromal infiltrates, suggesting that these alterations might not be a consequence of local cytokine effects. PMID- 2228312 TI - Patterns of expression of the p53 tumour suppressor in human breast tissues and tumours in situ and in vitro. AB - An extensive series of histological sections reflecting the various states of normal breast tissue, and a range of benign and malignant lesions, were examined for the expression of the p53 protein using a panel of anti-p53 antibodies. In 2 separate series the results of using frozen or methacarn-fixed, paraffin-embedded sections were compared. Strong positive staining for p53 was detected in over 50% of the malignant lesions when frozen sections were used. This number fell to just over 20% when methacarn-fixed sections were examined. In neither series was any p53 staining seen in normal breast or in the benign lesions. Studies by Western blotting on breast cell lines confirmed that this histological signal is due to a pronounced over-expression of the p53 protein. Earlier studies show that this over-expression is associated with mutation of the p53 gene. Mutation of the p53 gene with over-expression of the mutant protein is therefore one of the most frequent specific genetic changes in malignant breast cancer. PMID- 2228313 TI - Abelson murine leukemia virus transforms preneoplastic Emu-myc transgene-carrying cells of the B-lymphocyte lineage into plasmablastic tumors. AB - E mu-myc transgenic mice were back-crossed to BALB/c mice up to back-cross generation 3. The offspring that included transgene-carrying and -negative mice in approximately equal proportions were randomly divided into 2 groups. Thirty four mice (group I) were treated with pristane, followed by A-MuLV, and 40 (group II) were injected with A-MuLV alone. Altogether, 16 lymphoid tumors developed in group I and 17 in group II. Nine of the tumors in group I and 4 in group II appeared as ascitic tumors. The ascites contained lymphoblasts and 10 to 45% plasmacytoid cells. These tumors were designated as plasmablastic lymphomas (PLs). All tumors except one were transgene-positive and did not carry translocations. An exceptional tumor in group I carried a variant 6;15 translocation but not the transgene. It obviously corresponds to the regular Abelson + pristane-induced plasmacytoma. Among 11 tested PLs, 10 had a single retroviral insertion site, while one tumor showed 3. Among 18 untreated transgenic descendants (group III), chosen randomly during serial back-crosses, 15 (83%) developed lymphomas, with no sign of plasmacytoid differentiation. The incidence was comparable in all 3 groups, assuming 50% of the mice in groups I and II to be transgenic. The time distribution of tumor development was also similar. Spleen cells from transgene-carrying mice with no clinical sign of lymphoma were infected in vitro with A-MuLV and transplanted i.p. into BALB/c recipients. PLs developed in 26 of 31 pristane-treated recipients, but in only one of 18 untreated recipients. One of 6 PLs tested was monoclonal, whereas the remaining 5 were oligoclonal. They all expressed v-abl. These results show that some of the preneoplastic B-cells that expressed constitutively active myc transgene turned into plasmablasts after infection with A-MuLV. Full development of their neoplastic potential was facilitated by the presence of pristane granuloma. PMID- 2228314 TI - Detection of colonic growth factors using a human colonic carcinoma cell line (LIM1215). AB - Although the colonic mucosa is one of the most rapidly proliferating epithelial tissues in the body, little is known about the factors that direct this proliferation. In this report we have studied the parameters of both a mitogenic and a clonogenic assay for detecting potential colonic growth factors (CGF). Using a colon carcinoma cell line (LIM1215), which has retained a number of the properties of normal colonic mucosa, we have assayed a range of mitogenic factors for CGF activity. 3H-thymidine incorporation by the LIM1215 cell line was stimulated by low concentrations of epidermal growth factor and basic fibroblast growth factor and, to a lesser extent, by higher concentrations of interleukin-1 and insulin-like growth factor 1. The cells did not respond to a range of other mitogens and lymphokines. Optimal clonogenic response in a soft-agar assay was obtained using a primary pituitary extract. PMID- 2228315 TI - Immunochemical comparison of transformation-associated protein and secreted phosphoprotein. AB - Transformation-associated protein (TAP) has been detected in MSV-M-transformed rat cell lines as glycosylated, weakly phosphorylated protein of molecular weight (Mr) 66,000 and 68,000. In the ts-MSV-M-transformed rat kidney cell line (6m2), the synthesis of TAP and the v-mos gene product is temperature-sensitive and accompanies the expression of transformation phenotypes. Therefore, TAP potentially plays a role in cellular transformation. On the other hand, SPP represents a family of glycosylated phosphoprotein with apparent Mr ranging from 42,000 to 69,000. SPP has been detected in osteoblasts and in avian and murine retrovirus-transformed rat and mouse epithelial cells. Therefore, the potential relatedness of TAP and SPP was studied. Using the 6m2 cells, we found that SPP was strongly phosphorylated and was synthesized at both the permissive (33 degrees C) and non-permissive (39 degrees C) temperatures. By contrast, TAP was weakly phosphorylated, and was synthesized, as we found previously, only at the permissive temperature of 33 degrees C. Furthermore, in 35S-methionine incorporation studies, TAP became heavily labelled whereas SPP was not (consistent with its amino acid composition having few methionine residues). Using 125I-TAP in both immunoprecipitation and radioimmunoassays, it was found that an antiserum raised against SPP did not cross-react with 125I-TAP. Additionally, SPP has now been found in many human and rodent cells, while TAP thus far has only been detected in MSV-transformed rat cells. These data suggest that structurally, TAP and SPP are not closely related phosphoproteins. PMID- 2228316 TI - Evidence for the role of 34-kDa galactoside-binding lectin in transformation and metastasis. AB - The endogenous Mr 34,000 galactoside-binding lectin (L-34) is found at elevated levels in a wide variety of neoplastic cells and correlative evidence suggests that it is involved in tumor metastasis in vivo and in transformation in vitro. We demonstrate here that introduction of recombinant L-34 into tumorigenic, weakly metastatic UV-2237-cl-15 fibrosarcoma cells results in an increased incidence of experimental lung metastases in syngeneic and nude mice. Transfection of normal BALB/c-A31 cloned fibroblasts with functional L-34 results in acquisition of anchorage-independent growth and in morphological transformation in vitro but not in tumorigenicity in vivo. These results provide direct evidence that the cellular expression of L-34 is associated with some aspects of transformation and with metastasis, but not with tumorigenicity per se. PMID- 2228317 TI - Tumor necrosis factor-alpha and interleukin-1 alpha production in cachectic, tumor-bearing mice. AB - Weight-stable mice bearing a syngeneic, methylcholanthrene-induced, rapidly growing tumor lost approximately 22% of their lean tissue, became significantly hypoalbuminemic and had a marked increase in serum amyloid P concentrations during progressive tumor growth. Tumors from cachectic mice were producing both TNF-alpha and IL-1 alpha in vivo as documented by the presence of TNF-alpha and IL-1 alpha mRNA and immune-reactive protein for IL-1 alpha. Only spleens from tumor-bearing mice had statistically significantly elevated quantities of IL-1 mRNA. In general, alterations in tissue concentrations of IL-1 mRNA in tumor bearing animals agreed qualitatively with those found in endotoxin-stimulated, non-tumor-bearing control mice. However, endotoxin-stimulated mice had significantly elevated tissue concentrations of TNF mRNA in spleen and livers, while TNF mRNA levels were not significantly increased in any host tissues. Cytokine mRNA levels in tumor tissue were not higher than those found constitutively in various tissues from non-tumor-bearing control animals. Plasma from tumor-bearing mice and endotoxin-stimulated controls contained high levels of IL-6 but low (endotoxin-stim.) or no measurable levels (tumor-bearing) of either IL-1 or TNF. When tumor cells from cachectic mice were placed into long term cell culture, immune reactive TNF-alpha and IL-1 alpha were produced, but IL 6 bioactivity ws not produced in measurable amounts. PMID- 2228318 TI - Progestin induction of 17 beta-hydroxysteroid dehydrogenase enzyme protein in the T-47D human breast-cancer cell line. AB - Steroid regulation of 17 beta-hydroxysteroid dehydrogenase (17-HSD) was studied in the T-47D human breast-cancer cell line, using a radioimmunoassay. In addition, 3 mRNA species (2.4, 1.4, and 0.9 kb) specific for the enzyme were shown to be present in these cells. All the synthetic progestins tested (ORG 2058, R5020, medroxyprogesterone acetate) significantly increased the immunoreactive enzyme protein concentration, while other types of steroids, such as testosterone, oestradiol and dexamethasone, were ineffective. The progestin specific induction of 17-HSD was dose-related and was maximum in about 5 days. An antiprogestin, RU 486, when used in combination with synthetic progestins, blocked the progestin-induced increase of 17-HSD concentration very effectively. A good correlation was observed in the different experiments between the enzyme activity and the immunoreactive 17-HSD concentration. We conclude that progestins induce 17-HSD in T-47D cells and that the induction occurs via an increased accumulation of enzyme protein. PMID- 2228319 TI - Oncogene expression of FANFT- or BBN-induced rat urothelial cells. AB - Proto-oncogene expression by cultured urothelial cells prepared from the bladders of male F344 rats that had been treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined. Although all of the cultured cells showed varying degrees of anchorage independent growth, only 9 of them were transplantable into nude mice. A Northern blot technique was employed for the detection of proto-oncogene transcripts. The c-Ha-ras transcripts were detected in all the cultured urothelial cells prepared from the carcinogen-treated rats and in normal urothelial cells. However, the transcript levels were several-fold higher in the former than in normal cells. Increased expression of p21, as determined by immunohistochemical techniques, was also observed in all the original bladder tissues from which the cultures were derived. c-myc transcripts were detected in the cells from carcinogen-treated rats but not in the normal cells. The presence of myc product in hyperplastic urothelial lesions and carcinomas of original bladder tissues was confirmed by immunohistochemical methods. Transcripts of mos, erb B, Ki-ras, abl and src were not detected. Since increased expression of c-myc and c-Ha-ras were present in both transplantable and non-transplantable cell lines, and the expression of p21 occurs in preneoplastic cells, this suggests that elevated expression of these 2 genes may be an early genetic event during bladder carcinogenesis in the rat and further alteration of these 2 genes or mutation of additional genes may be required for the completion of malignant transformation. PMID- 2228320 TI - Retardation of metastatic tumor growth after immunization with metastasis specific monoclonal antibodies. AB - The influence of 4 murine monoclonal antibodies (MAbs) directed against surface determinants of a metastasizing rat adenocarcinoma (BSp73ASML) on metastatic spread was evaluated and compared to their in vivo binding as well as to the induction of a humoral anti-MAb response, especially with respect to the development of anti-idiotypic (ID) antibodies of the internal image type. In a protocol of explicit immunization, all 4 MAbs transiently inhibited metastatic growth. Survival was prolonged only with one MAb (4.4ASML). With another MAb (1.1ASML), directed against a new variant form of CD44, metastatic growth was accelerated after transient retardation. Retardation of metastatic growth correlated with the humoral anti-MAb response. This accounted for the isotype- as well as for the idiotype-specific response. An exception was noted after immunization with MAb 1.1ASML. Rats with high levels of anti-1.1ASML antibodies, which inhibited binding to the tumor cells (internal image-type antibodies) showed accelerated metastatic spread. Data are interpreted to mean that MAb induced inhibition of metastatic spread may be based on 2 independent mechanisms: blockade of metastasis-associated epitopes (i.e., with MAb 1.1ASML) and induction of an anti-mouse Ig response. In the latter case it was irrelevant whether the response was isotype- or idiotype-specific. PMID- 2228321 TI - Epidermal growth factor receptors and EGF-responsiveness of the human breast carcinoma cell line PMC42. AB - PMC42 is an early-passage, well-differentiated, pleiomorphic human breast-cancer cell line. It expresses an average of 2.4 x 10(5) EGF receptor (EGFR) sites per cell when cultures are assayed using a radioreceptor assay. This is a relatively high figure for breast-carcinoma cell lines. Its responses to epidermal growth factor (EGF) were analyzed morphologically and by flow cytometry and immunocytochemistry. PMC42 responded in vitro to EGF with morphological changes, inhibition of "doming" and an increase in DNA synthesis in serum-containing medium in confluent or near-confluent cultures. When EGF receptor sites were localized immunocytochemically in PMC42, they were found to be variably expressed on the membrane of cells grown in the absence of EGF, with discrete areas of strong and weak cells of different morphological appearances; flow cytometry indicated a 10-fold range in EGFR levels between individual cells. Cultures maintained in the presence of EGF were less heterogeneous in their morphology and had a predominantly cytoplasmic, relatively uniform localization of EGFR with down-regulation of membrane EGFR levels. EGF-stimulated cultures were stained simultaneously for the presence of EGFR and the proliferation-related antigen Ki 67 and analyzed by both flow cytometry and immunocytochemistry. No correlation was observed between Ki-67 positivity and level of EGFR expression by individual cells. Electron microscopic localization of receptor sites demonstrated that the receptors were concentrated predominantly on the lateral and basal membranes. These results show that the PMC42 line reflects a number of the properties of heterogeneous breast tumours in situ. It may also continue to express growth factor receptors in a manner that reflects their topographical distribution on normal luminal breast epithelial cells. PMID- 2228322 TI - A multicenter double-blind study of sulglycotide versus sucralfate in nonulcer dyspepsia. AB - Nonulcer dyspepsia remains to this date a clinical disease entity that is diagnosed and treated empirically by considering such patients potential ulcer carriers and treating them accordingly with H2 antagonists. The purpose of this study was to assess the therapeutic effectiveness of sulglycotide in patients with nonulcer dyspepsia in a random double-blind trial vs sucralfate. One hundred and eighty-seven consecutive patients with nonulcer dyspepsia were treated with sulglycotide (oral, 200 mg t.i.d. for 6 weeks, n = 93) or with sucralfate (oral, 1 g t.i.d. for the same length of time, n = 94). Drug effectiveness was evaluated in terms of apparent clinical symptom modifications, fiberoptic endoscopy findings and histological aspects of biopsy specimens. Both treatments resulted in prompt abatement of the clinical complaints of nonulcer dyspepsia and the improvement of macroscopic gastritis at endoscopy. These results confirm the usefulness of cytoprotective drugs in nonulcer dyspepsia characterized by gastroduodenal inflammation. PMID- 2228323 TI - Drug trials on healthy volunteers in Yugoslavia. AB - Ninety-seven healthy volunteers who participated in different clinical trials (phases III and IV) in a clinical pharmacology unit were interviewed over the period December 1988-February 1990 using questionnaire method. The aim of the investigation was to analyze the examinees' occupational distribution, the degree of insight in the trials they participated in, their opinion about the remuneration they get and their estimate of the importance or inconveniences of numerous trial elements. Only 39 volunteers (40.2%) were members of medical staff: 17 (17.5%) physicians, 17 (17.5%) medical students and 5 (5.2%) nurses. The volunteers assessed the importance of different elements related to the trial marking them from 1-5. They were more afraid of possible adverse drug reactions (ADR) occurring during the trial (median 3.87) than of those that might occur afterwards (2.94). Significant was their concern about the kind of investigated drug (3.49). "Potential contribution of the trial to the medicine and society" (3.30) and "length of time spent in the laboratory" (3.17) followed. The conduct of clinical trials on healthy volunteers in Yugoslavia and legal regulations are discussed at the end of the paper. PMID- 2228324 TI - Measuring the bronchial effects of bronchodilating drugs in healthy subjects with methacholine provocations: theophylline protects against induced bronchoconstriction in a dose-dependent manner. AB - To assess whether it would be possible to use methacholine (MCH) provocation tests with healthy subjects in the evaluation of bronchodilatory drugs, an intravenous infusion of theophylline ethylenediamine in increasing doses of 2.5, 5.0 and 7.5 mg/kg was given in random order to nine healthy non-smoking volunteers in a single-blind, placebo-controlled study. Dose response slope (DRS = maximal decline [%] in pulmonary function/the maximum dose of MCH [mumol]) was used to estimate airway reactivity. DRS was calculated to FEV1 (DRSFEV1) and to area under the flow-volume curve (AEFV, DRSAEFV). The bronchial reactivity was first tested with a standard MCH provocation method. An abbreviated, single-dose, method was used in the measurement of the effects of theophylline. The DRS-values obtained from the short method did not differ from those obtained from the standard one (p = 0.86, for DRSFEV1 and DRSAEFV), and correlation between these two methods was good (r = 0.93 and 0.98 for DRSFEV1 and DRSAEFV, respectively [p less than 0.001]). Serum theophylline concentrations achieved were (mean +/- SEM) 32.4 +/- 0.9, 63.7 +/- 3.3 and 93.4 +/- 3.3 mumol/l, which differed significantly from each other (p much less than 0.001). An inverse linear relationship between the serum theophylline concentration and the airway reactivity was observed with both indexes (r = -0.54, p less than 0.01 for DRSFEV1 and r = -0.65, p less than 0.001 for DRSAEFV). Even the lowest dose, which produced serum concentrations well under the therapeutic range, protected significantly (p less than 0.05) against MCH induced bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228325 TI - Comparative effects of rifampin and/or probenecid on the pharmacokinetics of temazepam and nitrazepam. AB - The pharmacokinetics of nitrazepam and temazepam were investigated in 16 healthy volunteers before and after seven days of the administration of rifampin 600 mg/d and/or probenecid 500 mg/d. In order to determine the endoplasmatic reticulum enzyme function, 6-beta-hydroxycortisol excretion and antipyrine pharmacokinetic parameters were evaluated. After the administration of rifampin, the total body clearance of antipyrine and nitrazepam increased by 87% and 83%, respectively. After the combined treatment with rifampin and probenecid, the elimination of the two drugs was also increased, even though to a lesser extent (33%, 31%). After the administration of probenecid only, the total clearances of antipyrine and nitrazepam were decreased by 22% and 25%, respectively. The urinary clearance of the antipyrine metabolites also decreased. In norantipyrine and 4-OH-antipyrine, this was due to a significant reduction of glucuronide fraction (211 +/- 32 to 159 +/- 26 mg, and 259 +/- 39 to 191 +/- 25 mg). The sulphate fraction of norantipyrine increased by 18% and that of 4-OH-antipyrine by 21%. Apart from a reduced excretion of the glucuronide fraction, the pharmacokinetics of temazepam were neither altered significantly by probenecid nor by rifampin. According to the outcome of this investigation, probenecid seems to bring about not merely an inhibition of phase II but also an inhibition of phase I metabolization. PMID- 2228326 TI - Lithium treatment and the geriatric population. AB - The present review attempts to highlight selective concerns with regard to the use of lithium in the geriatric population. Several points as pharmacokinetics, prophylaxis, side-effects, intoxication deserve particular emphasis in relation to the elderly patient and are discussed. Furthermore, since the potential for drug interactions is greatly increased because of the greater number of drugs these patients take, the clinical significance of some drug interactions is also reported. PMID- 2228327 TI - Intramuscular atropine in healthy volunteers: a pharmacokinetic and pharmacodynamic study. AB - In a randomized, double-blind, placebo controlled crossover study, the pharmacokinetics and some clinically important pharmacodynamic effects of intramuscular atropine (dl-hyoscyamine) were studied in 6 healthy male volunteers. The plasma concentrations of l-hyoscyamine were analyzed by radioreceptor assay (RRA) and the plasma concentrations of dl-hyoscyamine by radioimmunoassay (RIA). The absorption rate and the elimination rate of dl hyoscyamine and l-hyoscyamine were comparable (tmax = 8.40 vs 8.67 min, t1/2el = 2.95 vs 2.43 h, dose 0.02 mg/kg) but the mean maximum plasma concentration of dl hyoscyamine was 2.9 times and the mean AUC value 6.0 times higher than that of l hyoscyamine which indicates a kinetic difference between the enantiomers. The concentrations of d-hyoscyamine calculated from the dl- and l-hyoscyamine concentrations reached maximum between 1 and 2 h after drug injection. The renal excretion of l-hyoscyamine occurred mostly in 6 h (34% of the dose) and no conjugated drug forms were detected. The increase in heart rate was observed only after the higher dose (0.02 mg/kg) and it was significant between 30 min and 2 h. The plasma concentrations of l-hyoscyamine and the change in heart rate expressed as percentages showed a linear correlation: concentrations under 0.5 micrograms/l caused slowing of rate, higher concentrations caused acceleration. Also, the antisialagogue effect (30 min-3 h) correlated with plasma concentrations. PMID- 2228328 TI - The College Drinking Attitude Scale: a tool for alcohol education program assessment. AB - The development and validation of the College Drinking Attitude Scale (CDAS) are described. Based on a sample of over 4,000 college students, an item analysis, internal consistency analysis, and criterion validity analysis procedures were performed. The author concludes that the CDAS is a valid and reliable instrument that could be used to assess responsible attitudes toward the use of alcohol among college students. PMID- 2228329 TI - Ketamine--can chronic use impair memory? AB - Ketamine, a congener of phencyclidine (PCP), can produce a range of psychological effects which have led to its nonmedical use. Recent discoveries concerning the effects of ketamine and similar substances in the brain suggest that they may interfere with memory processes when given acutely and may affect synaptic plasticity when given chronically in high doses in certain animal models. It is thus of interest to examine the consequences, if any, of chronic use in humans. A case is here presented of long-term, high-dose ketamine use, in which the user described impaired recall and attention, and a subtle visual anomaly persisting after cessation of the habit. This history is considered in the context of other relevant studies. PMID- 2228331 TI - Existence, effectance, esteem: from gambling to a new theory of human motivation. AB - A study of gamblers' motives leads to the formulation of a new theory of human motivation. The theory states that humans have three basic interrelated needs: (1) a need to confirm their existence, (2) a need to affirm their worth, and (3) a need to produce effects (be a causal agent). The theory further states: (4) When they produce desired (intended) effects, they experience pleasure (e.g., joy); and when they fail to produce desired effects, they experience displeasure (e.g., disappointment). (5) The principle of least effort and (6) mental, emotional, and bodily blocks act as impediments to the confirmation of existence, to the affirmation of worth, and to the production of effects. PMID- 2228330 TI - Instrument for the measurement of individual and societal attitudes toward drugs. AB - Due to the importance of the relation between attitudes and the experimentation with and use of drugs among adolescents, an instrument was developed composed of individual and societal attitudes toward drugs. A pilot study was carried out on the basis of which a questionnaire containing 63 items was constructed. This questionnaire was given to the research sample of 566 Israeli high school students aged 15-17. Three criteria were used to determine the final version of the instrument, which contains 55 items. Factor analysis revealed seven factors: curiosity and willingness to use drugs, social concern, individual freedom, attribution of positive characteristics to drugs, perceived harmfulness of drugs, perceived characteristics of drug users, and legalization of drugs. Reliability of the factors ranges from alpha = 0.64 to alpha = 0.88; reliability of the entire questionnaire is alpha = 0.89. A short version of the questionnaire consisting of 27 items (alpha = 0.80) was developed for special populations. These findings suggest that the Green Individual and Societal Attitudes Toward Drugs Questionnaire can be employed as a diagnostic tool to identify potential drug experimenters, and as a planning and evaluation measure to preventive drug educational programs. PMID- 2228332 TI - The Addiction Severity Index: predicting relationship to a hospital and a professional. AB - The Addiction Severity Index was developed to be a useful instrument in treatment planning for the substance abuser. Multivariate statistical tests were conducted on the questionnaire for a clinical sample of 190 males at a Veterans Administration hospital. When the desire for psychological treatment with a specific person was taken into consideration, the overall predictive validity of the instrument in designating discharge accounted for 69% of the variance rather than 24% of the variance. This finding could challenge the myth that substance abusers and patients from lower socioeconomic levels are not psychologically minded and not capable of being engaged in psychological process treatment. This finding is also relevant to governmental concerns for quality assurance and cost effectiveness, since it can be utilized to both improve treatment planning and delete irrelevant documentation and assessment procedures. PMID- 2228333 TI - From theory to practice: the planned treatment of drug users. Interview by Stanley Einstein. PMID- 2228334 TI - Personality and alcohol and marijuana use: patterns of convergence in young adulthood. AB - This study looks at similarities and differences between users of alcohol only and users of both alcohol and marijuana ranging in age from 18 to 24. Assessment of use included measures of use intensity, use context, use functions, and use problems. Personality variables included measures of temperamental/affective tendencies, evaluative appraisals of self, and stress associated with negative appraisals of one's self and one's environment. The two strongest patterns of convergence were found to be similar across groups and to be consistent with mean differences between both groups. It is concluded that the two patterns characterize different segments of the population of users. PMID- 2228335 TI - Perception of intoxication and blood alcohol concentration of drinkers in social settings. AB - This study examined associations among perception of intoxication, blood alcohol concentration (BAC), discriminability of internal physiological sensations, and awareness of external stimuli related to the number of drinks consumed of subjects in social drinking settings. A total of 156 randomly selected individuals consented to be interviewed as they walked by preselected drinking establishments, and afterward provided a breath sample to determine BAC. This study found that drinkers in social settings can make at least crude estimates of their level of intoxication, and that the accuracy of these estimates decreases as BAC increases. PMID- 2228336 TI - The relationship between child and adult psychopathology in children of alcoholics. AB - Children of alcoholics (COA) and adult children of alcoholics (ACA) are identified as a group with recognizable characteristics resulting from their childhood situation. The major conclusions in the literature regarding the psychosocial consequences of being a COA are reviewed. Two lists, one for children and one for adults, are provided which summarize these consequences. Variables which influence these effects are discussed, as well as the development of adult psychopathology from child psychopathology. Treatment strategies designed to prevent this development are reviewed briefly and a resource table for COAs is presented. PMID- 2228337 TI - AIDS-related risk behaviors among substance abusers. AB - Ninety-two substance abusers were surveyed about AIDS-related risk behaviors. The questionnaire administered elicited information on demographics, sexual practices, substance abuse, and risk behaviors involving the use of needles. Results indicated an appropriate base of prevention knowledge and patients' efforts to modify vulnerability to HIV exposure. Nevertheless, patients continue to engage in behaviors resulting in HIV exposure and transmission. PMID- 2228338 TI - Drug abuse prevalence in western Canada and the North West Territories: a survey of students in grades 6-12. PMID- 2228339 TI - From theory to practice: the planned treatment of drug users. Interview by Stanley Einstein. PMID- 2228340 TI - Role of digoxin in right ventricular failure due to chronic cor pulmonale. AB - The effect of digoxin in the treatment of decompensated chronic cor pulmonale was investigated in a randomized double-blind, cross-over, placebo-controlled trial. A total of 34 successive patients with evident right heart failure were included in the study. The mean maintenance daily dose of digoxin was 0.30 +/- 0.03 mg with the mean serum level of 1.7 +/- 0.7 nmol/L. The severity of heart failure was assessed according to a clinicoradiographic scoring system (Heart Failure Score). The heart failure worsened during the placebo-period in eight (23.5%) patients (four with atrial fibrillation, two with a third heart sound (S3), one with a cardiothoracic ratio of more than 0.5 and one with sinus rhythm). By regression analysis, the heart failure significantly worsened only in the subgroup of patients with atrial fibrillation. Digoxin was successfully (without worsening of the heart failure) discontinued in 26 (76.5%) patients. No significant improvement was observed in the patients with S3 gallop. It was concluded that digoxin had no beneficial effect in chronic cor pulmonale patients with heart failure, except in those with atrial fibrillation. PMID- 2228341 TI - Lack of interaction between famotidine and warfarin. AB - In eight healthy male volunteers taking daily subtherapeutic doses of warfarin (mean daily dose = 4.0 mg), the addition of famotidine 40 mg once-a-day for seven days did not alter the prothrombin time profile, thrombotest coagulation time or total warfarin steady-state plasma concentration. Plasma peak concentration, time to peak concentration and area under curve for famotidine were not affected by the co-administration of warfarin. However the plasma half-life of famotidine was slightly, but statistically significantly longer (p less than 0.05) during maintenance treatment with warfarin (mean +/- s.e.m.: 2.58 +/- 0.14 h versus 2.96 +/- 0.16 h respectively). PMID- 2228342 TI - Protection of the upper gastrointestinal mucosa: the role of antacids. AB - Experiments performed in animals and in healthy human subjects suggest that antacids increase prostaglandin synthesis and have a cytoprotective effect on gastroduodenal mucosa. To investigate this hypothesis, the ability was evaluated of an antacid containing an aluminium/magnesium hydroxide combination (Maalox TC) to modify prostanoid production at the gastric level in 28 patients with gastric antral ulcer of various sizes in different stages of activity with or without erosive gastritis. After the antacid treatment, a significant prostaglandin E2 reduction was observed, together with a significant 6-keto-prostaglandin F1 alpha increase, but there was no thromboxane B2 variation at antrum level, nor any significant modification of prostanoid production at body level. The decreased prostaglandin E2 levels, detected after treatment with the antacid combination, may be due to lesion improvement, decreased synthesis or increased catabolism by mucosal cells, to a drop in this prostaglandin production by inflammatory cells. As far as 6-keto-prostaglandin F1 alpha is concerned, the obtained data confirm the results reported by other authors in healthy human subjects. The increase of this prostaglandin could enhance blood flow, resulting in a protective effect. PMID- 2228343 TI - Ranitidine in children with peptic ulcer and patients with pancreatic cystic fibrosis. AB - This article describes experience of the use of ranitidine in children with peptic ulcer and patients with pancreatic cystic fibrosis. Ranitidine proved to be efficacious and well tolerated, the percentage of healing being 89.4%. Ranitidine was also used in subjects with gastritis from Campylobacter pylori, obtaining rapid regression of subjective symptoms. Administration of ranitidine to cystic fibrosis patients improved the efficacy of the pancreatic extract, with consequent enhancement of digestive compensation. PMID- 2228344 TI - Imipramine pharmacokinetics in depressed geriatric patients. AB - Pharmacokinetics of single dose (25 mg i.m.) of imipramine was studied in geriatric and young adult patients with mood disorders requiring antidepressant treatment. Imipramine and its principal metabolites were determined by means of a high performance liquid chromatography method with electrochemical detection. Serum concentrations analysis was performed according to a bicompartmental open model. A relationship between age and kinetic parameters such as area under the curve, elimination phase constant, half-life and total body clearance was observed. Significant differences were demonstrated between elderly and young adult patients when comparing these parameters. It is concluded that geriatric patients treated with imipramine should receive doses of about 60% of those of young adults. PMID- 2228345 TI - Metabolic effects induced by L-carnitine and propionyl-L-carnitine in human hypoxic muscle tissue during exercise. AB - An experimental model was developed to investigate some metabolic effects of strenuous exercise in hypoxic muscle tissue of human volunteers. The incidence of carnitine supplementation was studied, assuming as marker the thiobarbituric acid reaction products analysed in plasma samples collected during the course of the protocol programme. Propionyl-L-carnitine appears to antagonize in a significant degree the damaging effects of muscle fatigue combined with hypoxic status. Under these conditions the detoxifying role played by propionyl-L-carnitine, previously reported in various tissues and in other pathological conditions, appears to be relevant, although further studies are needed to elucidate the pharmacodynamics of this molecule. PMID- 2228346 TI - Towards an integrated model of group psychotherapy with the elderly. AB - Three current approaches to the group therapy of the cognitively intact, depressed elderly are reviewed. Examination of the strengths and limitations of these three models--self psychology, developmental considerations such as reminiscing and life review, and cognitive-behavioral therapies--points in the direction of the usefulness of an integrated model. The main objectives of an integrated approach include: stabilization of the individual's sense of self, establishment of interpersonal competence, and enhanced mastery over the affects of depression and demoralization. Clinical illustrations are provided to demonstrate the practical considerations in this model of group therapy. PMID- 2228347 TI - Group therapy with sexually abused boys: leadership, projective identification, and countertransference issues. AB - Group therapy is an essential component of the treatment of sexually abused children. Since the painful effects associated with the abuse are often dissociated or acted out, the group leaders learn of the affective experience of the abuse through the process of projective identification. The leaders must be aware of this process, set limits on the abusive acting out in the group, and help moderate, label, and empathize with the affect. It is through this difficult process that the children have a chance to reintegrate and work through their abuse experiences so they no longer feel compelled to act them out through repetitive abusive relationships. Specific leadership, countertransference, and projective identification issues in group therapy with sexually abused boys are discussed. PMID- 2228348 TI - Activities and games for group psychotherapy with sexually abused children. AB - As increasing attention is given to the practice of group psychotherapy with sexually abused children, clinicians are using games and activities designed to address issues related to sexual abuse and its prevention. This paper describes how specific games and activities can be used in group therapy with child victims. These games and activities include: prevention films, role plays, and communication board games. Benefits and risks associated with the use of these resources are also discussed. PMID- 2228350 TI - Brief group psychotherapy in relapse prevention for alcohol dependent patients. AB - The effects of brief group psychotherapy in relapse prevention were tested. The groups focused on the clients' capacity to formulate their own treatment goals, including controlled drinking, programmed relapse, and total abstinence. Twelve months after completion of the eight-week outpatient group treatment, thirty-five clients were followed up. There appeared to be no harmful effects as a result of the treatment. Nobody in the follow-up group had a deteriorated drinking pattern as compared to pretreatment data. The follow-up results were significantly better than before treatment and also than in a comparison group of alcohol dependent patients. It seemed as if those patients who could benefit from the treatment had a shorter duration of abuse and had a later onset of uncontrolled drinking compared to those who continued with a negative drinking pattern and the dropouts. The clients assigned the positive treatment effects to course leaders' encouragement of personal decision making, increased awareness of risk situations, and improved coping skills. The group situation in itself seemed to be of special importance for this result. The degree of structure implemented by course leaders allowed a free and respectful openness to develop between group members. PMID- 2228349 TI - A controlled study of effectiveness and patient suitability for short-term group psychotherapy. AB - A controlled, clinical trial investigation of short-term psychoanalytically oriented group psychotherapy (STG) was conducted which included eight psychotherapy groups led by experienced therapists. Patient psychological mindedness (PM) was investigated as a selection criterion and prognostic variable. Seventy-nine psychiatric outpatients experiencing prolonged or delayed grief reactions were matched for level of PM and then randomly assigned to STG or a wait list. There was repeated measurement of several areas and sources of outcome. Results indicated a strong main effect for STG but not for PM on outcome, and minimal evidence for an interaction effect. Benefits were maintained at six-month follow-up. Psychological mindedness emerged as highly predictive of attrition. A clinical discussion is presented wherein the efficacy of STG is considered as reflecting a good patient-treatment match. PMID- 2228351 TI - The different patterns of group climate critical incidents in high and low cohesion sessions of group psychotherapy. AB - The total data set for this study consisted of 958 critical incidents from high and low cohesion sessions in person-centered group psychotherapy. These incidents were typically noted on a group climate questionnaire at the end of each session. Altogether 211 clients and students participated in twenty-six groups. The high cohesion sessions were dominated by the following cohesion dimensions in rank order: self-disclosure and feedback (24.0%); attraction and bonding (20.2%); listening and empathy (20.0%); process performance and goal attainment (15.0%); and support and caring (10.6%). The corresponding rank order for the low cohesion sessions was strikingly different: avoidance and defensiveness (43.5%); conflict and rebellion (22.2%); and self-disclosure and feedback (8.9%). Apparently then, there are very different patterns of critical incidents in high and low cohesion sessions of group psychotherapy. PMID- 2228352 TI - Eating problems and calorie intake levels in Swiss adolescent athletes. AB - The purpose of this study was to investigate the incidence of eating disorders (ED), calorie intake levels and body fat measures in Swiss female athletes. Thirty athletic and 34 non-athletic adolescent Swiss females were assessed for tendencies toward eating disorders and weight preoccupation using the Eating Disorders Inventory (EDI). Calorie intakes were calculated from 7-day intake records. Body compositions were determined using skin-fold measures. The athletes were divided into two groups: Those whose activities emphasize leanness (12 gymnasts, means age = 12.5 +/- 1.1 yrs), and those whose activities do not emphasize leanness (18 swimmers, mean age = 12.8 +/- 0.9 yrs). The non-athletic school-girls (mean age = 13.4 +/- 1.2 yrs) served as controls. ANOVA indicated that the gymnasts had lower body fat levels (p less than 0.01) and consumed fewer total calories (p less than 0.05) than swimmers or controls, but all groups consumed similar calories per kg/body weight. Chi square analysis indicated that similar numbers of swimmers (11%), gymnasts (1%) and controls (6%) were exceptionally preoccupied with weight (p greater than 0.05). However, more swimmers (38%) scored high on the body dissatisfaction subscale of the EDI than the gymnasts (1%) or control (9%) (p less than 0.01). In fact, more swimmers scored high on 3 subscales of the EDI compared to the other groups (p less than 0.05). It appears that disturbances in eating behaviors are not limited to sports that emphasize leanness. PMID- 2228353 TI - Oxidation of exogenous carbohydrate during prolonged exercise in fed and fasted conditions. AB - The oxidation of glucose and fructose ingested during moderate exercise performed on a cycle ergometer (120 min, 52% VO2max) was compared in ten young males fasted (n = 5) or fed (n = 5) before exercise. The subjects ingested randomly 1.33 g/kg body weight (approximately 96 +/- 9 g) of either enriched 13C-glucose (G), 13C fructose (F), or water only (W); the solutions were evenly distributed over the exercise period. The fasted subjects began the three exercises with a lower blood glucose (P less than or equal to 0.05 for F only) and insulin (P less than or equal to 0.05) levels and a higher free fatty acid (FFA) concentration (P less than or equal to 0.05) than the fed ones. Throughout the exercise period, blood glucose level was maintained in fasted as well as in fed group for G and F ingestions, while it decreased (P less than or equal to 0.05 at the 100th min in fasted subjects) with water ingestion. Insulin level was similar in both fed and fasted conditions with F and W ingestions and lower than G trials for the fed subjects. For the three ingestions, FFA was lower (P less than or equal to 0.05) in the fasted than in the fed group over the exercise period. Over the 2-h period of exercise, a greater (P less than or equal to 0.05) amount of exogenous F was oxidized in the fasted (49 +/- 6 g) than in the fed (36 +/- 5 g) group, which represent 31% and 20% of the total carbohydrate energy supply, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228354 TI - Zinc metabolism in the athlete: influence of training, nutrition and other factors. AB - Serum zinc was measured four times (October, January, March and May) in six young male athletes during a nine-month sporting season in relation to eleven other parameters. A significant decrease in serum zinc was observed after five months of intensive training (all values remaining in the normal range). This cannot be explained by changes in dietary habits, plasma protein concentrations, hormonal changes nor by the existence of minor infectious or inflammatory pathologies. The dietary intakes seemed adequate. These results support the hypothesis that zinc status may be slightly altered in the high-level athlete. PMID- 2228355 TI - Effects of training specificity on the lactate threshold and VO2 peak. AB - We examined the effects of training specificity on the lactate threshold (LT) and VO2peak. Sixteen male subjects completed VO2peak/LT protocols on the cycle ergometer (CE) and treadmill (TM) before and after a training program. The subjects were assigned to run training (N = 5), cycle training (N = 6), and control groups (N = 5). Subjects trained 4 day/week for 10 weeks at approximately 89% of pre-training VO2peak. Results indicated that run training increased VO2 at LT (VO2LT) within both the CE and TM protocols (17.9 to 22.5 ml/kg.min-1 for CE, 22.7 to 36.0 ml/kg.min-1 for TM, p less than 0.05) with the 58.5% increase in VO2LT for TM being greater than the 30.3% increase for CE (p less than 0.05). Cycle training resulted in a 38.7% increase in CE VO2LT (19.7 to 27.4 ml/kg.min 1, p less than 0.05) with no significant improvement in TM VO2LT (23.6 to 24.0 ml/kg.min-1). Similar increases in VO2peak were observed for CE and TM protocols for both cycle and run training groups (VO2peak increased by 11.9 to 20.7% in both CE and TM regardless of training mode). No changes were observed in the control group for any variable. The present data suggest that increases in LT resulting from training may be specific to the mode of exercise. PMID- 2228356 TI - Prediction of oxygen uptake on a bicycle wind-loaded simulator. AB - The primary purpose of this study was to determine the accuracy of estimating oxygen uptake (VO2) from the flywheel revolution rate of a bicycle wind-loaded simulator. VO2 at four different flywheel revolution rates was measured on a Findlay Road Machine (FRM). Ten male trained cyclists, 10 male untrained cyclists, 10 female trained cyclists and 10 female untrained cyclists served as subjects. Significant curvilinear relationships (P less than 0.01) were found between road speed estimated from flywheel revolution rate and VO2 expressed as 1.min-1, ml.kg-1.min-1, 1.min-1.m-2 (r = 0.97, 0.96, 0.98, respectively). The absolute standard error of the mean VO2 was 0.21 l.min-1 (9.6%), 3.71 ml.kg-1.min 1 (11.5%) and 0.10 l.min-1.m-2 (7.9%), respectively. The relationship between VO2 and speed was similar to that reported during road cycling. To determine the magnitude of between-machine differences in VO2, six subjects randomly performed cycling using two different FMR. Significant (P less than 0.05) differences between machines were found at only the highest speed. The present study indicates that it is possible to accurately predict VO2 from flywheel revolution rate using a FRM. Since the FRM appears to approximate the resistance a cyclist experiences on the road and allows cyclists to use their own bicycle, it provides a good alternative to traditional laboratory ergometers. PMID- 2228357 TI - Comparative lactate kinetics after short and prolonged submaximal exercise. AB - Arterial blood lactate concentrations were determined in two groups of eleven males before, during and after near 2 W.kg body mass-1 bicycle exercise. One group of subjects cycled for 3 min, whereas the second group exercised for 60 min. All the lactate curves during recovery could be fitted to a bi-exponential time function consisting of a rapidly increasing and a slowly decreasing component. This typical evolution pattern indicates that the two-compartment model which has been proposed to represent the movements of lactate after short exercise applies also to recovery from prolonged exercise. Lengthening exercise duration decreased (respectively 10% and 28%) the value of both velocity constants of the fits to the lactate recovery curves, with the difference (28%) being statistically significant for the velocity constant describing the slowly decreasing part of the curves. This result indicates that extending exercise from 3 to 60 min impairs the ability to remove lactate after the exercise. PMID- 2228358 TI - Proprioceptive facilitation of muscle tension during unilateral and bilateral knee extension. AB - The effects of double neuromuscular facilitation (DNF) in unilateral movements and of quadruple neuromuscular facilitation (QNF) in bilateral movements were studied in 42 physically active college-age male subjects. Results showed a 10.4% significant increase of maximal knee extension torque output when unilateral extension was preceded by a knee flexion on an isokinetic exerciser and a 16.7% increase of maximal torque in the bilateral condition of simultaneous alternating flexion-extension when compared to the simultaneous extension movement. Consequently, the increased peak torque observed in the unilateral and bilateral experimental conditions in which knee extension was preceded by a knee flexion appears to be the result of a combination of neuromuscular influences and stored elastic energy. PMID- 2228359 TI - Resistance exercise effects on plasma cortisol, testosterone and creatine kinase activity in anabolic-androgenic steroid users. AB - Anabolic-androgenic steroids (AS) users have been reported to have an improved ability to withstand exhaustive resistance workouts and to recover more rapidly. The purpose of this investigation was to study the effects of AS usage on the cortisol (C), testosterone (T) and creatine kinase (CK) response to a resistance training session. Eleven trained body builders and power lifters (5.0 +/- 1.6 training years, mean +/- SD), 5 AS users (SU) and 6 nonusers (NU), completed a standardized resistance training session consisting of 10 sets of back squats at preset percentages of the subject's 1 RM max. Blood samples were obtained at rest, immediately post exercise and 24 hours after the exercise session. SU had significantly lower T at rest. Neither group exhibited a significant change in T at 1 min or at 24 h post exercise. Both the NU and SU exhibited a significant increase in CK at 1 min post exercise (129 +/- 23.3 U.l-1, 81 +/- 15.3 U.l-1, respectively), with the NU response significantly greater than the SU. After 24 h, CK for NU was significantly elevated (171.9 +/- 54.5 U.l-1) above resting level. In contrast, CK for SU had returned to resting level. NU had a significant increase in cortisol (C) (p less than 0.05) at 1 min post exercise (156.8 +/- 10.9 nmol.l-1), while the SU cortisol was not significantly changed. By 24 h C for the NU returned to resting level. The results of this investigation support the concept that AS users have a diminished CK response and an altered stress response to a single bout of resistance exercise. PMID- 2228360 TI - Hypothalamic-pituitary-testicular axis function in endurance-trained males. AB - The hypothalamic-pituitary-testicular (H-P-T) axis was evaluated in groups of endurance-trained (TRG) and untrained (UNT) males. Each group was subjected to: 1) a 4-h resting hormonal profile [testosterone (T), free-testosterone (FT), estradiol (E2), luteinizing hormone (LH), prolactin (PRL), and cortisol (C)], 2) a dopamine antagonist (DA; 10 micrograms.kg-1 body weight) challenge to the pituitary-testes, and 3) a gonadotropin-releasing hormone (GnRH; 120 micrograms.kg-1 body weight) challenge to the pituitary-testes. Compared to UNT, the TRG resting T (4.8 +/- 0.7 vs 7.1 +/- 1.2 ng.ml-1, p = 0.05) and PRL (3.3 +/- 1.4 vs 7.0 +/- 2.3 ng.ml-1, p = 0.09) were lower while LH was elevated (15.0 +/- 1.8 vs 11.8 +/- 1.5 mIU.ml-1, p = 0.06). The DA challenge produced a greater integrated PRL response in the TRG (2962.7 +/- 265.1 ng +/- ml-1.min) than in the UNT (1735.3 +/- 282.0 ng.ml-1.min; p = 0.01). No significant changes were observed in T following the DA-induced PRL rise. The TRG had a blunted LH response (817.2 +/- 111.6 mIU.ml-1.min) following the GnRH injection as compared to the UNT (1493.7 +/- 213.4 mIU.ml-1.min; P less than 0.02). T levels were significantly (p less than 0.03) increased in both groups by the LH rise after the GnRH challenge (TRG = 9.9 +/- 5.0%; UNT = 8.6 +/- 9.9%, respectively), but no significant between group differences were observed. Results suggest endurance training produces an enhanced PRL and attenuated LH release by the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228361 TI - Exercise cardiac contractility in men and boys: a recovery echocardiographic study. AB - Previous reports have suggested that children possess limited cardiac functional reserve during exercise compared to young adults. In this study, echocardiography was performed immediately after maximal treadmill exercise to measure left ventricular dimensions and shortening fraction (SF) in college men, and these values were compared to previous results in a post-exercise echocardiographic study of prepubertal boys. Post-exercise SF, change in SF from rest, and percent change in SF from rest were all significantly greater in the post-pubertal subjects. In both men and boys changes in SF following exercise were related to reductions in left ventricular end-systolic dimension, with only minor reductions observed in end-diastolic dimension. These findings support the concept that prepubertal subjects may have inferior myocardial function with exercise when compared to young adults. PMID- 2228362 TI - Isolated fractures of the capitate: use of nuclear medicine as an aid to diagnosis. AB - Fractures of the capitate are considered to be uncommon injuries of the wrist, however, delay in diagnosis may result in prolonged disability and avascular necrosis. Two cases are reported in which an isolated fracture of the capitate was diagnosed with a 99mTc-MDP nuclear medicine bone scan and confirmed with CT scan or repeated conventional x-rays. These two cases illustrate that an isolated fracture of the capitate should be considered in an individual presenting with persistent wrist pain of traumatic origin, even when conventional x-ray views are negative. The nuclear medicine bone scan can be a useful investigative tool and serve to guide further radiological investigations. PMID- 2228363 TI - Care or convenience? On the medical-bureaucratic model of commitment of the mentally ill. PMID- 2228364 TI - The future of homicide offenders. Results from a homicide project in Copenhagen. AB - As a part of a Copenhagen homicide project, 52 released homicide offenders were followed during a mean period of 9 years. Pessimistic expectations were confirmed as post-release rates of criminality, psychiatric admission, and suicide were all very high. By logistic regression analyses, young age by release, and long stay in prison were found to increase the risk of further criminality, and previous psychiatric admission was found predictive of future admission. The problems in using logistic regression analysis on variables--all of whom may be viewed as "parallel" indicators of a common tendency to adverse behaviors--are discussed. In conclusion, the results have been used for a tentative division of homicide according to the offender-victim relationship into intra-family homicide and extra-family homicide. In intra-family homicide the most important dimension seems to be the psychic state of the offender, in extra-family homicide more impact should be attributed to the social dimension. PMID- 2228365 TI - Accounting for predictions of dangerousness. PMID- 2228366 TI - The predictors of insanity acquittal. PMID- 2228367 TI - Effects of ultimate opinions on juror perceptions of insanity. PMID- 2228368 TI - The prevalence of depression, alcohol abuse, and cocaine abuse among United States lawyers. PMID- 2228369 TI - Erysipelas. PMID- 2228370 TI - A dermatologic gazetteer. PMID- 2228371 TI - Chondrodysplasia punctata (Conradi disease). PMID- 2228373 TI - Action in international dermatology. PMID- 2228372 TI - Geographic dermatology. PMID- 2228374 TI - Familial pityriasis rotunda. AB - Pityriasis rotunda is a rare dermatosis characterized by circular, dusty scaling, dyschromic patches, quite asymptomatic and mostly described in Japanese and blacks. The authors have seen three cases of pityriasis rotunda in a Sardinian family that are to be added to two other similar reports. The patients were all in good health. An interesting feature was the association with favism. On inquiry it was discovered that many more members of the family were affected by either or both pathologies. The authors believe this condition to be a form of minor acquired ichthyosis of which Sardinia could be an ethnic center. PMID- 2228375 TI - Morphea coexisting with lichen sclerosus et atrophicus. AB - A 65-year-old woman presented with four autoimmune diseases. These include morphea, lichen sclerosus et atrophicus, insulin-dependent diabetes mellitus, and autoimmune thyroid disease. The relationship between morphea and lichen sclerosus et A is discussed, as is the link between these conditions and autoimmunity. PMID- 2228376 TI - Reactions in leprosy. A study of 250 patients in a multidrug therapy project, Baroda District, Gujarat, India. PMID- 2228377 TI - Histoid lepromas of lepromatous leprosy. AB - Histoid lepromas are a rare eruption in patients with lepromatous leprosy. A 59 year-old man from India with lepromatous leprosy who developed histoid lepromas and who was dapsone resistant was studied. These tumors resembled cutaneous metastases. This Indian man is to our knowledge the first patient to be reported with this rare disorder in the continental United States. PMID- 2228378 TI - Nodularity of nerves in treated leprosy. AB - Ten patients with fully treated paucibacillary leprosy, mainly tuberculoid, had asymptomatic nodules present along the peripheral nerves that persisted even after the skin lesions had completely subsided and treatment was stopped. Histopathology of the nodules revealed no signs of activity of the disease. The evolution, follow-up care, and significance of these nodules are discussed. PMID- 2228379 TI - Outbreak of Paederus dermatitis in southern Nigeria. Epidemiology and dermatology. PMID- 2228380 TI - Epidemiological studies on head lice infestation in Israel. I. Parasitological examination of children. AB - Of 3,079 children in a medium-sized community near Jerusalem, 11.2% were found to be infested with living lice and eggs and another 23.4% had only nits. Boys and girls were equally infested. The incidence of infestation was highest among children 4-11 years of age. About 78% of the infested children had from one to ten lice. Approximately 80% of the infested children had nits that were 2-5 cm away from the scalp. Boys with medium length hair and girls with short hair showed the highest incidence of lice infestation. Children with brown and red hair were more infested than those with black and blond hair. Boys and girls with straight and wavy hair were more infested than those with curly and frizzy hair. PMID- 2228381 TI - Insect bite lesions in Kuwait possibly due to Leptodemus minutus. PMID- 2228382 TI - Conditions for dermatological treatment in a developing country. AB - Malaria is the most common disease in the world, with 100 million new cases a year. Statistics, however, seem to show that skin diseases are next on the list of most common diseases in developing countries. PMID- 2228383 TI - Acroangiodermatitis. A clinical variant of stasis dermatitis. PMID- 2228384 TI - Erosive pustular dermatosis of the scalp. PMID- 2228385 TI - Hyperkeratosis of the nipple and areola in a patient with cutaneous T-cell lymphoma. PMID- 2228386 TI - Naftifine cream 1% compared with miconazole cream 2% in dermatophytosis. PMID- 2228387 TI - "Zoological classification" of skin diseases. PMID- 2228388 TI - First report of leprosy and psoriasis occurring together. PMID- 2228389 TI - Systemic sclerosis: scleroderma. PMID- 2228390 TI - Resting metabolic rate and postprandial thermogenesis in polycystic ovarian syndrome. AB - To determine whether the high frequency of obesity in women with polycystic ovary syndrome (PCO) is related to a defect in energy expenditure, resting metabolic rate (RMR) and the thermic response to a standard meal were compared in 10 obese PCO women, nine obese but otherwise normal women, and 11 lean women. All groups were matched with respect to age and fat-free mass and the two obese groups were matched for degree of obesity. RMR was measured by indirect calorimetry for 3 h on two days: (1) in the postabsorptive state; and (2) after a 720 kcal (3014 kJ) liquid mixed meal. The thermic effect of food, calculated as 3 h postprandial minus fasting RMR, was significantly greater for the lean [52.9 +/- 5.5 kcal/3 h (221 +/- 23 kJ/3 h)] than the obese [17.2 +/- 5.1 kcal/3 h (72 +/- 21 kJ/3 h)] and the PCO women [22.8 +/- 5.2 kcal/3 h (95 +/- 22 kJ/3)], P less than 0.001). The thermic effect of food was negatively related to percent body fat (r = 0.694, P less than 0.001). Resting metabolic rate did not differ significantly among the three groups, and was strongly related to fat-free mass (r = 0.687, P less than 0.001). These results confirm previous reports of blunted thermogenesis in obese individuals, but provide no evidence of altered resting metabolic rate or postprandial thermogenesis in women with PCO compared with normal women of similar degree of obesity. PMID- 2228391 TI - Invited commentary: phenylpropanolamine and the medical literature: a thorough reading is required. PMID- 2228392 TI - Phenylpropanolamine and caffeine use among diet center clients. AB - We surveyed phenylpropanolamine (PPA) use and overuse among 309 diet center clients. Fifty-one percent of all subjects surveyed reported using PPA drugs: 44 percent used cold medicines and 16 percent used diet aids. Twenty-two percent of diet aid users and 7 percent of cold medicine users reported that they deliberately used more than the dosage recommended to improve efficacy. Among diet aid users, 59 percent also regularly consumed caffeine. Despite package warnings, individuals who had been told by their doctors that they were hypertensive used PPA products as often as normotensive individuals. PPA, the fifth most frequently used drug in the USA, is contained in over-the-counter (OTC) diet aids as well as OTC and prescription cold medicines. Severe adverse drug reactions (ADRs) including hypertensive crisis, stroke and death have been attributed to PPA products. Clinical studies have shown that using greater than recommended doses of PPA and using PPA in combination with caffeine may increase the risk of ADRs. Overweight patients may be particularly at risk for ADRs to PPA because they are likely to be hypertensive and to use diet aids. We recommend informing diet center clients of the potential dangers of consuming PPA products, especially more than the recommended dose, in the presence of hypertension, and when other sympathomimetic drugs are being taken. PMID- 2228393 TI - The association of body fat distribution with lifestyle and reproductive factors in a population study of postmenopausal women. AB - We examined the cross-sectional association of fat distribution with a number of lifestyle and reproductive factors in a random sample of 40,980 postmenopausal women, aged 55 to 69 years. The relationship of weight history with current fat distribution was also explored. Body fat distribution, defined by the ratio of waist-to-hip circumferences (WHR), was most strongly related to body mass index (BMI). WHR was also significantly and negatively associated with physical activity, alcohol consumption, and education, and was significantly positively associated with age, cigarette smoking, and a number of reproductive factors, such as history of infertility, number of live births, age at first live birth, and replacement estrogen use. WHR was not related to past BMIs, after adjusting for current body mass. The best-fit final regression model included (beta +/- s.e.) age (0.003 +/- 0.0001), BMI (0.02 +/- 0.0005), a curvilinear term for BMI ( 0.0002 +/- 0.00001), greater than high school education (-0.007 +/- 0.001), cigarette smoking (0.02 +/- 0.001), alcohol drinker (-0.005 +/- 0.001), and number of live births (0.001 +/- 0.0002). The model R2 was 0.21. BMI (R2 = 0.18) and age (R2 = 0.02) accounted for most of the variation in WHR. The association of these lifestyle and reproductive factors with WHR suggests that the deposition of fat in the abdominal versus the gluteal region may be influenced somewhat by factors other than overall adiposity and genetics. PMID- 2228394 TI - Genetic and behavioral influences on body fat distribution. AB - Genetic and environmental influences on four measures of body fat distribution - subscapular/triceps ratio (STR), waist/hip ratio (WHR), and regression-adjusted subscapular skinfold and waist circumference indices - were examined in 265 pairs of white male twins, ages 59 to 70 years, who participated in the third examination of the National Heart, Lung, and Blood Institute's Twin Study. Skinfold indices of fat distribution were not highly correlated with indices based on body circumferences (r = 0.26-0.37 for the four possible correlations). After adjustment for overall obesity, the heritability of the adjusted subscapular skinfold index was substantial (h2 = 0.60, P less than 0.001), as were estimates for both subscapular and tricep skinfolds individually. By contrast, heritability of the STR was low and of borderline statistical significance (h2 = 0.24, P = 0.06). Heritability for the WHR (h2 = 0.31, P = 0.07) was also low. Although higher estimates were observed for the adjusted waist circumference index (h2 = 0.46, P = 0.02) and for the component circumferences, these were not clearly due to genetic influences. Among behavioral influences, cigarette smoking was strongly related to the WHR and adjusted waist circumference index (P less than 0.0001). A crude measure of total physical activity was weakly, inversely related to WHR (P = 0.06), and slightly more strongly related to the adjusted waist circumference index (P = 0.01). Skinfold indices were unrelated to either behavior. We conclude that: (1) skinfold indices measure a different dimension of fat distribution than circumference indices; (2) there is evidence for a genetic influence on subcutaneous fat distribution, but less evidence for such an influence on the WHR; (3) behavioral factors appear to be more important in determining the WHR than subcutaneous fat patterning. PMID- 2228395 TI - Direct measurement of abdominal fat by dual photon absorptiometry. AB - We have assessed photon absorptiometry as a new technique for direct measurement of the abdominal fat percentage (AF%). The accuracy of the method was assessed in vitro with phantoms consisting of ox muscle, lard, and a mixture of both. The results showed good linearity (r = 0.999). The in vitro reproducibility and the in vivo reproducibility were s.d. = 2.0 and s.d. = 2.8 (AF%), respectively. The AF% was measured in 148 healthy post-menopausal women and found to correlate with other measurements of fatness, such as total body fat per cent (r = 0.82, P less than 0.001), body mass index (r = 0.79, P less than 0.001) and the ratio of waist to-hip circumference (r = 0.59, P less than 0.001). The waist-to-hip ratio, an important predictor of cardiovascular disease, was more tightly correlated with AF% than with body mass index. We conclude that this method may be a useful new research tool for direct measurements of abdominal fat, a possible cardiovascular risk factor. PMID- 2228396 TI - The effect of long-term dexfenfluramine treatment on 24-hour energy expenditure in man. A double-blind placebo controlled study. AB - In order to investigate the effect of long-term treatment with dexfenfluramine (dF) on 24-hour energy expenditure (EE), 10 obese females were studied in a double-blind design. Shortly before and 4 weeks after cessation of a 13 months treatment period with either dF (30 mg/day) or placebo (PL) the 24-hour EE was measured. The measurements were performed using a 24 m3 direct heat sink calorimeter with continuous real time measurements of evaporative and sensible heat losses. The patients performed a standardized program of exercise, rest and meals. The measurements were performed at 24 degrees C and at a humidity between 3 and 11 g/m3. Discontinuation of dF treatment did not change energy expenditure significantly from placebo, neither when expressed in kJ/kg lean body mass nor in kJ/kg body weight. After cessation of treatment total 24-hour EE decreased likewise nonsignificantly by 2.9 percent in the dF group and by 4.0 percent in the PL group. EE measured over 24 hours was subdivided into day and night periods and into resting energy expenditure as well as a measurement of the heat losses over a period of 3 hours after a meal. This subdivision of the EE showed similar nonsignificant differences. The conclusion is therefore that dF possesses no significant thermogenic effect during long-term administration in human obese subjects. PMID- 2228397 TI - Overweight and mortality in Mexican Americans. AB - The Geriatric Research Center (GRC) table of desirable weights is based on the mortality experience of holders of 4.2 million policies issued by 25 life insurance companies in the USA and Canada. The GRC table defines optimum weight for-height as the weight range which is associated with below average mortality for a given age and height group. People who fall outside this range, i.e. overweight or underweight, experience above average mortality for their age and height group. We classified 3176 Mexican Americans and 1841 non-Hispanic whites who participated in the San Antonio Heart Study according to the GRC table and found that Mexican Americans were less likely than non-Hispanic whites to be underweight and more likely to be overweight. The two effects did not offset one another, however, and fewer Mexican Americans were found to be in the 'just right' range. If the mortality experience of the population which generated the GRC table (largely non-Hispanic) applied to Mexican Americans, these results imply that Mexican Americans should have higher mortality rates than non-Hispanic whites. Vital statistics data from the state of Texas for the years 1979-81, however, fail to corroborate this prediction. Beyond age 45 years, an age range in which obesity and obesity-related disorders would be expected to exert an important influence on mortality, age-specific and age-adjusted all cause mortality was at last as good if not better in Mexican Americans than in non Hispanic whites. These results could not be explained by ethnic differences in body fat distribution, since fat was less favorably distributed in Mexican Americans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228398 TI - Nutrient oxidation patterns and protein metabolism in lean and obese subjects. AB - The immediate metabolic response to eating has been compared in a group of grossly obese subjects (W/H2 = 45) with that in lean controls (W/H2 = 22). Dietary intake of energy for obese subjects was based on their estimated basal energy expenditure for ideal body weight (given at an hourly rate of 3 X BMR over a 4-h period). Lean subjects were measured twice: control 1 with the same intake of energy as the obese in terms of ideal body weight and control 2 with the same energy intake in relation to each subject's measured resting energy expenditure (2.2 X REE). The changes in energy expenditure and nutrient disposal with the onset of eating have been assessed by a method of combined respiratory gas analysis and intravenous infusion of 13C-labelled leucine. Leucine kinetics were used to quantitate rapid changes in protein oxidation and to assess protein synthesis and degradation. 1) Total energy expenditure was 20-30 per cent greater in obese subjects than lean subjects in fasting and feeding. Energy expenditure expressed per kg fat-free mass, from D2O dilution, was similar in obese and lean subjects in both fasting (5.8 v. 5.5 kJ/kg FFM/h) and feeding [6.7 v. 6.3 (Control 2) kJ/kg FFM/h]. 2) The onset of eating was associated with increased carbohydrate and protein oxidation with decreased fat oxidation in both lean and obese individuals. In obese subjects, however, both the decrease in fat oxidation and the increase in protein oxidation were significantly smaller (P less than 0.05) than the corresponding increments in lean subjects (Control 2). 3) The rate of protein synthesis was significantly (P less than 0.05) higher in obese subjects both in the fasting state (99 v. 84 mumols leucine/kg FFM/h) and in the fed state [94 v. 67 (Control 2) mumols leucine/kg FFM/h]. The rate of protein degradation was also higher in obese individuals in fasting (117 +/- 6 v. 106 +/- 4 mumol leucine/kg FFM/h) and feeding [65 +/- 4 v. 54 +/- 6 (Control 2) mumol leucine/kg FFM/h] though these differences are not statistically significant (P greater than 0.05). 4) The observed differences between obese and lean individuals in protein and energy metabolism in the fasted state and in the immediate response to eating do not support a hypothesis of greater metabolic efficiency in obesity. PMID- 2228399 TI - Effect of dl-fenfluramine on thermic effect of food in humans. AB - To determine whether dl-fenfluramine increased metabolic rate in humans, hourly indirect calorimetry measurements were made on 16 nonobese males over a 5 h period under each of four conditions: placebo/no meal, placebo/meal, 60 mg dl fenfluramine/no meal, and 60 mg dl-fenfluramine/meal. Drug administration was double-blind and a Latin square design was used with treatments separated by 7 days. To confirm that active drug was administered when assigned, subjective sensations were measured by questionnaires administered three times during each treatment. Metabolic rate (kcal/min) during the four treatments was compared by analysis of variance over the entire 5 h and at the end of the measurement period. The 750 kcal (3140 kJ) meal increased metabolic rate over the fasting conditions (0.160 +/- 0.035 kcal/min, P less than 0.0005) and the combination of fenfluramine and meal caused a further significant increase beyond that found with placebo and meal (0.072 +/- 0.035 kcal/min, P less than 0.025). At the end of the measurement period, metabolic rate during the placebo/meal treatment had returned to the level of the fasting treatments. In contrast, during the fenfluramine/meal condition, metabolic rate was still elevated (0.173 +/- 0.04 kcal/min, P less than 0.003). The results of this study suggested that fenfluramine increased metabolic rate by potentiating the thermic effect of food. PMID- 2228400 TI - The association of waist hip ratio and angiographically determined coronary artery disease. AB - Body fat distribution as measured by the ratio of waist circumference to hip circumference (WHR) is now accepted as an important risk factor for a number of diseases. This study evaluated the association of WHR and coronary artery disease (CAD). Measurements included the subjects' height, weight, waist girth, hip girth, significant CAD on coronary angiography, and cholesterol levels. A history of myocardial infarction, angina, diabetes or hypertension was obtained from subject interviews. The subjects were analyzed in two age groups: younger than age 60 (88 men and 39 women) and age 60 or older (85 men and 63 women). For older women the relative odds of CAD comparing women at the 75th percentile of WHR to women at the 25th percentile was 3.67 (P = 0.003), with a 95 percent confidence interval of 1.57-8.57. The relative odds was reduced to 2.80 after adjusting for all other risk factors. WHR was significantly associated with angiographic evidence of CAD in all women combined after adjusting for age (P = 0.0004), but it was not significantly associated with CAD in younger women or in men. The results suggest that in older women the risk of CAD increases with a greater percentage of body fat in the abdomen. PMID- 2228401 TI - Nutrient intake of obese children in a family-based behavioral weight control program. AB - The caloric and nutrient intakes, weight, percent overweight and growth of obese and lean children aged 8-12 were compared at baseline and after the obese children participated in a six month family-based behavioral weight control program. At baseline there were no significant differences in the caloric, fat, calcium, iron, vitamin A, vitamin C, thiamin, and riboflavin intakes, or height percentiles of the obese and lean children. After six months the obese children significantly decreased their calorie, protein, fat, and carbohydrate intake, while the lean children significantly increased their protein intake. The percent overweight of the obese children decreased significantly (-18.3 percent), with no changes in percent overweight of the lean children (-0.1 percent). Both the obese (+4.3 cm) and lean (+3.8 cm) children grew significantly over six months, with no significant changes in height percentiles. At baseline and six months both groups exceeded at least two-thirds of the RDA for all nutrients studied. PMID- 2228402 TI - Hunger/craving responses and reactivity to food stimuli during fasting and dieting. AB - One group of fasting obese patients and one group of dieting obese patients were instructed to report their feelings of hunger and craving on a continuous basis before and during a three-week treatment period. Once a week they were also exposed to food slides to measure their reactivity to food stimuli. The frequency of hunger/craving responses and reactivity to food stimuli showed radically different changes over time in the fasting and dieting groups. During the last week of fasting, reactivity to food slides was completely abolished, and the frequency of hunger/craving responses was close to zero. Only slight changes of frequency of hunger/craving responses and reactivity to food stimuli were observed in the dieting group. The results suggest that the frequency of hunger/craving responses and reactivity to food stimuli show parallel decreases during fasting, but no changes during dieting. PMID- 2228403 TI - Body composition, muscle and fat pad changes following two levels of dietary restriction and/or exercise training in male rats. AB - This study examined the effects of exercise training on conservation of lean mass during moderate and severe dietary restriction in male Sprague-Dawley rats. Eight rats each (48 total) were assigned to one of three levels of dietary restriction (ad lib., AL; moderate, MR; severe, SR) and to one of two activity levels (cage confined, CC; or treadmill exercised, E) for a 10-week period. Post-intervention, the AL-E (91 percent), MR-CC (84 percent), MR-E (86 percent), SR-CC (66 percent) and SR-E (68 percent) groups all weighed less than the AL-CC group (427 +/- 4.3 g). Exercise training resulted in conservation of lean mass (protein + water + ash) at the moderate but not severe levels of dietary restriction. Further examination showed that this was mostly water since no between-group differences existed at any given diet level for protein or ash mass. Exercise training did elicit conservation of left ventricular heart muscle mass at both the moderate and severe levels of dietary restriction. In contrast, gastrocnemius muscle mass was conserved or maintained only at the moderate dietary restriction level. Thus, the level of dietary restriction appears to affect the ability of exercise training to elicit conservation of both total lean mass and the mass of individual muscles during diet-induced body mass reduction. PMID- 2228404 TI - The effect of dietary restriction on gastrin secretion in the obese Zucker rat. AB - It has been hypothesized that G-cell hyperplasia secondary to increased food consumption in the obese Zucker rat was responsible for the hypergastrinemia observed in vivo and from the isolated perfused stomach preparation. This possibility was investigated in pair-feeding experiments wherein the food intake of obese animals was restricted to match that of lean littermates from 5 to 8 weeks of age. Dietary restriction reduced the antral G-cell population of the obese rat to a similar level as that seen in lean animals, supporting the view that hyperphagia is the trigger for G-cell hyperplasia. However, basal gastrin levels measured in vivo and in vitro from the stomach preparation of the pair-fed obese animals were not significantly lower than those of obese animals fed ad libitum. Thus, abnormal feeding behavior in the obese phenotype cannot be directly related to gastrin hypersecretion and G-cell hyperplasia is not the primary cause of hypergastrinemia. PMID- 2228405 TI - The doubling of prolactin levels after a dry Finnish sauna may increase body fat stores. PMID- 2228406 TI - B cell secretion and insulin sensitivity in hypertensive and normotensive obese subjects. AB - To test the hypothesis that in obesity hypertension is associated with more pronounced hyperinsulinaemia and insulin resistance we compared plasma insulin levels and insulin sensitivity in a group of 6 obese subjects with untreated hypertension and in a group of 6 obese subjects with normal blood pressure. The two groups were similar for sex, age, body mass index and glucose tolerance. Six nonobese subjects served as controls. The study consisted of a 2-h hyperglycaemic clamp (steady-state plasma glucose = 11 mmol/l) and a 15-min insulin tolerance test (0.1 U/kg body wt). During hyperglycaemic clamp, insulin and C-peptide plasma levels were similar in normotensive and hypertensive obese subjects: the area under the plasma insulin curve was 36,000 +/- 3000 pmol/l X 120 min in the former and 34,000 +/- 1000 pmol/l X 120 min in the latter; the area under the plasma C-peptide curve was 298,000 +/- 26,000 pmol/l X 120 min in the former and 246,000 +/- 26,000 pmol/l X 120 min in the latter (P = n.s.). The ratio M/I between the amount of glucose metabolized (M) and the mean plasma insulin levels (I) during hyperglycaemic clamp was similar in the two groups: 0.59 +/- 0.09 in normotensive and 0.58 +/- 0.08 mg/min X m2 per pmol/l in hypertensive obese subjects (P = n.s.). Also the rate coefficient of glucose disappearance from plasma (K(itt)) after i.v. insulin injection was similar in the two groups (4.08 +/- 0.51 vs. 3.87 +/- 0.53 per cent/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228407 TI - Effects of a high-protein meal (meat) and a high-carbohydrate meal (vegetarian) on satiety measured by automated computerized monitoring of subsequent food intake, motivation to eat and food preferences. AB - We have examined the effects on satiety of equicaloric meals with different protein and carbohydrate content. Twenty normal weight healthy women were served cooked lunch meals made of commonly used natural food items with either a high protein (43 energy %) (a meat casserole) or a high-carbohydrate (69 energy %) (a vegetarian casserole) content in a counterbalanced repeated measures design. The subsequent ad libitum evening meal intake (4 h after lunch) was measured by a 'universal eating monitor' and subjective feelings of motivation to eat and food preferences were assessed repeatedly. At the subsequent evening meal subjects ate 12 per cent less (P less than 0.05) after the high-protein meal compared to the high-carbohydrate meal. There was no difference in motivation to eat between meals. This could partly be explained by a difference in palatability between the meals. The food-preference lists showed that before lunch there was relative preference for high-protein foods in favour of high-carbohydrate foods. After lunch either meal produced instead a relative 'aversion' for high-protein foods. This 'aversion' was greater after the high-protein lunch meal than after the high carbohydrate lunch meal. PMID- 2228408 TI - Fat distribution in relation to age, degree of obesity, smoking habits, parity and estrogen use: a cross-sectional study in 11,825 Dutch women participating in the DOM-project. AB - Fat distribution (waist/hip ratio) was assessed in a population of 11,825 women, aged 40-73 years, presenting for routine breast cancer screening (the DOM project in Utrecht) in the period 1984 to 1986. Waist/hip ratio increased with increasing Quetelet's index and age. Postmenopausal women did not have higher waist/hip ratios compared to premenopausal women after adjustment for Quetelet's index and age. In pre- and postmenopausal women, waist/hip ratio increased with increasing number of cigarettes smoked per day (while Quetelet's index decreased) and a positive linear relationship was found between parity and waist/hip ratio (also after adjustment for Quetelet's index and age). Age at menarche was strongly inversely related to Quetelet's index but was not related to waist/hip ratio. In postmenopausal women, waist/hip ratio was lower in women who reported to use oestrogens for menopausal complaints in comparison with similar women who did not, but this difference disappeared after adjustment for age and degree of obesity. This study emphasizes the role of some variables that are associated with fat distribution and are potential confounders of risk estimates of abdominal obesity. PMID- 2228409 TI - Genetic effects in the response of adipose tissue lipoprotein lipase activity to prolonged exercise. A twin study. AB - Our laboratory has reported large inter-individual differences in the metabolic response of adipose tissue to prolonged exercise in humans. The present study investigated the contribution of heredity in the metabolic changes of adipose tissue to prolonged exercise in 11 monozygotic and 10 dizygotic pairs of male twins, 18 to 27 years of age, studied immediately before and after a 90 min bout of exercise. The sum of 7 skinfold thicknesses and percent of fat from underwater weighing were used as body fat indicators (BFI). Subcutaneous adipose tissue was excised and fat cell weight (FCW) determined. The activity of adipose tissue lipoprotein lipase (LPL) released with heparin was also measured. BFI and FCW were identical in both types of twins. As previously reported, LPL activity was increased by exercise (P less than 0.01) in both type of twins. The changes observed for LPL activity were more similar in monozygotic twins than in dizygotic twins resulting in a significant level of inheritance (P less than 0.05). A genetic component for LPL activity supports the hypothesis that adipose tissue LPL could be genetically determined not only in its basal activity but also in response to stresses such as exercise. PMID- 2228410 TI - Prediction of body water and fat in adult Danes from measurement of electrical impedance. A validation study. AB - The purpose of the present study was to test the validity of the electrical impedance method for estimation of total body water and lean body mass in adult Danes with large differences of obesity and fat distribution, and to develop algorithms for estimation of body water, lean body mass and fat from measurement of impedance. The results of the electrical impedance method were compared in 139 Danes aged 35-65 years, to those of a four-compartment-model based on measurements of both total body potassium (whole body counting) and total body water (dilutometry). The comparison confirmed the validity of the impedance method. Equations for predicting body water and lean body mass in Danes are given. A significant difference was found between two instruments of the same model. In spite of the fact that the test resistance supplied by the manufacturer gave identical measurements, measurements on humans diverged on average by 31 ohm. A cross-validation study showed that most of the algorithms found in the literature for predicting lean body mass from impedance yield reliable results. PMID- 2228411 TI - Sex-specific vs. unisex body mass indices as predictors of non-insulin dependent diabetes mellitus in older adults. AB - In order to examine sex differences in the association of obesity with the risk of non-insulin dependent diabetes mellitus (NIDDM) when using the body mass index (BMI), we compared unisex body mass index classifications with sex-specific categories, as defined by the Metropolitan Life Tables, based on their utility in predicting the 12-year incidence of NIDDM in men and women. The present analysis included all 747 men and 969 women from a defined older caucasian population in Rancho Bernardo, California, who were 40 years of age or older at the baseline examination in 1972-1974 and who had complete diabetes-related data available then and between 1984-1987. The 12-year age-adjusted incidence rates for NIDDM increased with increasing BMI among women (all steps significant), but was significantly increased only in the most obese category of men (relative risk (RR) = 2.3, P less than 0.05 for men; RR = 3.8, P less than 0.001 for women). Men and women had nearly identical rates of NIDDM in this obese category. When identical (unisex) BMI cutpoints were used, results were the same; (RR = 2.4, P less than 0.05 for men; RR = 3.1, P less than 0.01 for women). These data indicate that unisex and sex-specific cutpoints for BMI identify the same sex specific patterns of association between obesity and risk of NIDDM. PMID- 2228412 TI - Adrenalectomy reverses the impaired pyrogenic responses to interleukin-beta in obese Zucker rats. AB - Interleukin-1 is an important endogenous pyrogen which stimulates thermogenesis in normal animals by a central action which is dependent on release of corticotrophin releasing factor (CRF). Central injection of murine recombinant interleukin-1 beta (IL-1 beta, 5 ng) in conscious lean (+/?) Zucker rats produced significant increases in resting oxygen consumption (VO2, 26 per cent), colonic temperature (1.3 degrees C) and thermogenic activity (mitochondrial GDP binding) of brown adipose tissue (BAT, 24 per cent). In contrast, genetically obese (fa/fa) Zucker rats showed nonsignificant changes in VO2 (4 per cent), temperature (0.5 degrees C) and BAT activity (0 per cent). Bilateral surgical adrenalectomy (ADX) dramatically enhanced the effects of IL-1 beta on VO2 (45 per cent) body temperature (1.8 degrees C) and BAT activity (44 per cent) in obese mutants, but only slightly increased responses in lean rats. These data suggest that impaired responses to IL-1 beta in obese mutants may be due to inhibitory actions of glucocorticoids on either prostaglandin synthesis or CRF release within the hypothalamus. PMID- 2228413 TI - Obesity: a biogenetic or biobehavioral problem. AB - A great deal of effort is being expended to investigate the biogenetic basis of the development and maintenance of obesity and the regulation of food intake. The task of developing and validating theoretical models of the regulation of food intake and its relationship to body weight is hampered by a lack of basic descriptive data. This study investigated the eating behavior of 96 obese women by conducting a microanalysis of 2-week baseline behavioral eating diaries. Subjects were in approximate energy balance consuming a high-fat diet (41 percent of kcal from fats) averaging 1978 kcal/day. Self-reported episodes of overeating and impulsive eating occurred frequently and were associated with situational antecedents such as eating in the car, snacking alone, friends, restaurants, availability of forbidden foods, craving sweets, tired, irritable, bored, depressed, and skipping meals. Markov chain analysis showed that overeating and impulsive eating were positively autocorrelated, suggesting the presence of an abstinence violation effect. These data suggest that eating behavior is often controlled by environmental, cognitive, and affective variables and that a complete understanding of obesity will require an integrated biobehavioral approach. PMID- 2228414 TI - Introduction to the symposium on energy expenditure and obesity. PMID- 2228415 TI - Energy expenditure and thermogenesis: animal studies on brown adipose tissue. AB - Thermogenesis in brown adipose tissue is now regarded as being a major component in the normal energy expenditure of laboratory rodents, and variations in the level of thermogenesis in the tissue are important in the regulation of energy balance. Defective thermogenic responses to diet or to cold have been shown to be central to the development of obesity in various rodent models. The quantitative importance of brown adipose tissue thermogenesis to energy expenditure in species other than rodents has not been established, but it is clear that the tissue is present in a wide range of mammals. In particular, active brown adipose tissue has now been identified in adult humans, as well as in newborn infants. PMID- 2228416 TI - Body weight regulation in obese and obese-reduced rats. AB - We previously developed a model of dietary obesity in adult male rats where duration of feeding a high fat diet (HFD; 60 percent of calories from fat) influences reversibility of the obesity following a reduction in dietary fat. In the model, rats fed the HFD for 4 months show an apparent complete reversal of obesity when switched to a low fat diet (LFD; 14 percent of calories from fat), but rats fed the HFD for 7 months show persistent obesity even when switched to the LFD. This model of dietary obesity is useful for studies of energy balance and energy requirements during obesity development and reversal. In the present study, rats fed the HFD for 4 or 7 months were switched to the LFD and, after weights stabilized, were subjected to food restriction followed by ad libitum refeeding. Food restriction (15 g/day of the LFD, or about 60 percent of usual control food intake) continued until body weights of the groups stabilized at new, reduced levels (about 2-2.5 months). This was followed by ad libitum refeeding of the LFD for 3--4.5 months. Rats fed the HFD for 4 months showed complete obesity reversal after 2 months of eating the LFD. They showed a similar response to food restriction to LFD controls, but surprisingly regained significantly more body weight, body fat and total body energy during refeeding than LFD controls. Rats fed the HFD for 7 months remained heavier and fatter than LFD controls after 2 months of eating the LFD. Despite losing more carcass energy than controls during food restriction, their body weights and body energy content stabilized at higher levels than LFD controls. During refeeding, they regained their obese state relative to controls. These results demonstrate that: (1) the duration of HFD feeding is an important factor in the reversibility of the obese state; (2) sustained HFD feeding produces an obese state that is defended more by a greater restoration of carcass energy during refeeding than by a preservation of carcass energy during food restriction; (3) sustained obesity appears to produce some reductions in energy requirements; (4) even a brief period of obesity may leave the rats prone to reattain an obese state when body weight is challenged. PMID- 2228417 TI - Genetic effects in human energy expenditure components. AB - It is increasingly recognized that variations in human energy expenditure are partly due to an influence of the genotype, even after control for the well established concomitants of energy expenditure. Using the technique of genetic epidemiology, we have found that about 40 percent of the variance in resting metabolic rate, thermic effect of food and energy cost of low to moderate intensity exercise (less than or equal to 5 times the resting metabolic rate) is explained by inherited characteristics. A significant genetic effect has also been reported for the level of habitual physical activity. The existence of a genotype-environment interaction has also been investigated. Thus, we have demonstrated that in response to chronic overfeeding, as well as negative energy balance, changes in the components of energy expenditure are partly determined by one's genotype. Taken as a whole, these observations consistently support the hypothesis that heredity plays a significant role on the variations in the various components of energy expenditure in humans. Further research should now be focused more on the identification of biochemical and molecular markers of these energy expenditure characteristics. PMID- 2228418 TI - The pathogenesis of obesity in man: results of studies on Pima Indians. PMID- 2228419 TI - Energy metabolism in obese patients before and after weight loss, and in patients who have relapsed. PMID- 2228420 TI - Assessment of energy expenditure in ambulatory reduced-obese subjects by the techniques of weight stabilization and exogenous weight replacement. AB - A technique based on a completely metabolizable liquid diet was developed rapidly to achieve weight stability (+/- 50 g/day) in experimental subjects. Weight stabilizing caloric intake was then used as an estimate of total daily energy expenditure (24 h EE) in a study of 10 ambulatory obese subjects before and after weight loss. In five control subjects 24 h EE fell by 928 +/- 121 kcal/day (3885 +/- 507 kJ/day) or 29 +/- 3 percent after a 22.6 +/- 1.2 percent weight loss achieved on a three month 700 kcal/day (2930 kJ/day) diet. To determine how much of this decrease was due to the reduced thermic effect of exercise (TEE) at the lower body weight, the remaining five subjects underwent progressive exogenous weight replacement during dieting to compensate exactly for their 21.0 +/- 5.2 percent weight loss. In the latter group 24 h EE fell by only 392 +/- 192 kcal/day (1641 +/- 804 kJ/day) or 12 +/- 5 percent (P less than 0.001). These data, along with indirect calorimetric measurements of resting metabolic rate (RMR), permitted the decrease in 24 h EE with weight loss to be divided into its component parts. Decreases in RMR, TEE and the thermic effect of food accounted for 30 percent, 52 percent and 18 percent respectively of the fall in 24 h EE. A reduction in TEE appears to make a greater contribution to the enhanced energy efficiency of ambulatory reduced-obese subjects than has been suggested by studies based on methods requiring greater subject confinement. PMID- 2228421 TI - Sphingomyelin synthesis in Fasciola hepatica. AB - Whole worms and/or homogenates of F. hepatica incorporate label from cytidine-5 diphospho[methyl-14C]choline,[1-14C]palmitoylCoA,[U- 14C]serine,[2 14C]methionine, [U-14C]glycine, [U-14C]threonine and [U-14C]aspartate into the various intermediates of sphingomyelin synthesis (ketosphinganine, sphinganine, sphingosine, ceramide and sphingomyelin). This suggests that sphingomyelin synthesis in F. hepatica occurs by a pathway similar to that found in mammals. However, there is some evidence that in F. hepatica 3-ketosphinganine may be N acylated prior to reduction and dehydrogenation. PMID- 2228422 TI - Taenia taeniaeformis: evasion of complement-mediated lysis by early larval stages following activation of the alternative pathway. AB - Activation of the alternative pathway of complement by T. taeniaeformis oncospheres and early stage metacestodes, although a factor in host defense against primary infection, does not directly lead to the killing of the parasite larvae observed prior to day 6 post-infection in innately resistant BALB/cByJ inbred mice. Immunogold labelling techniques clearly demonstrated tegument associated C3 on in vitro-activated oncospheres incubated with non-immune mouse sera. However, C5, a protease necessary for the assembly of the membrane attack complex, was not detected. Early stage larvae cultured from in vitro-activated oncospheres escaped membrane damage and survived incubation in non-immune sera from both BALB/cByJ and taeniid-susceptible C3H/HeDub mice. Comparisons of cobra venom factor-treated and untreated C5-deficient B10.D2osn mice revealed no significant differences in parasite burden and local eosinophil infiltration at 6 days post-infection, suggesting that the terminal arm of the complement system is necessary for the previously reported role of complement in resistance to primary infection in BALB/cByJ and C3H/HeDub mice. An in vivo test of chemotaxis indicated that although both complement-intact mouse strains examined responded to intraperitoneal injections of inulin, there were lower numbers of eosinophils in C3H/HeDub mice than in BALB/cByJ mice, perhaps pointing to possible mouse strain differences in C5a generation/catabolism or eosinophil ability to respond to C5a. Lectin-binding studies showed an affinity of PNA for the exposed surface of taeniid oncospheres and 4-day post-infection metacestodes; however, binding of lectin to the carbohydrate moiety did not inhibit complement activation. PMID- 2228423 TI - The in vitro adherence of murine eosinophils, neutrophils and non-induced and induced macrophages to infective larvae of Toxocara canis (Nematoda, Ascarididae). AB - Infective larvae of the parasite nematode Toxocara canis were incubated in vitro with murine eosinophils, neutrophils and non-induced and induced macrophages. The interactions between the different types of cells and the worms were observed in the presence or absence of immune mouse serum and/or complement. Cells showed considerable differences in the manner, duration and outcome of this interaction. Despite the adhesion of cells to the larvae of T. canis, there was no evidence of damage to the worms. Scanning and transmission electron microscopic observations suggest that the cells adhere to the cuticular surface via an electron-dense material. This material might play a protective role against the helmintotoxic capacity of the inflammatory cells. PMID- 2228424 TI - Gametocytogenesis induction by ammonium compounds in cultured Plasmodium falciparum. AB - Asexual parasites of a strain that seldom or never produce gametocytes in in vitro culture began gametocytogenesis after 24 h treatment with RPMI 1640 medium containing concanavalin A (final concentration, 10 micrograms ml-1) and ammonium carbonate (final concentration, 15 mM ml-1) or ammonium bicarbonate (final concentration, 15 mM ml-1). Gametocytogenesis was consistently observed from the 3rd day after the treatment. Concanavalin A enhanced gametocytogenesis induction by ammonium carbonate or ammonium bicarbonate, although concanavalin A does not itself have gametocytogenesis induction activity. Whereas no gametocytogenesis was observed after addition of concanavalin A and ammonium acetate (final concentration, 5-25 mM ml-1) or ammonium chloride (final concentration, 5-15 mM 1). Addition of ammonium compounds resulted in decrease of parasitemia, regardless of gametocytogenesis. PMID- 2228425 TI - Eimeria apsheronica in the goat: endogenous development and host cellular response. AB - Most first generation schizonts of Eimeria apsheronica developed in the jejunum; others were distributed throughout the small intestine and occasionally in the caecum. Some were also found in the mesenteric lymph nodes, which were oedematous and haemorrhagic. In the intestine, haemorrhage and congestion were seen before parasites were detected, and continued throughout all later stages. Schizonts occurred in the lamina propria and occasionally in the submucosa, where they sometimes caused a cellular inflammatory response. Schizonts were first seen at 8 days post-infection (DPI); they had poorly defined nuclei and were enclosed in a capsule-like wall. At 16 DPI, many had matured, had a mean size of 125 x 82 microns, and were filled with numerous spindle-shaped merozoites, which were in ranks and loops. At 18 and 20 DPI, when small white lesions (1-3 mm in diameter) were observed in the jejunum and elsewhere in the small intestine, a second generation of schizonts, macrogametes, microgametocytes and maturing oocysts were seen, in the epithelial cells of the small intestine and caecum. Their mean sizes, respectively, were: 26.2 x 18.9, 24.7 x 18.5, 30.2 x 21.7 and 26.6 x 19.3 microns. Macrogametes contained basophilic central and eosinophilic peripheral granules. The sexual stages were associated with a generalized cellular inflammatory response. PMID- 2228426 TI - Basophils in skin reactions of mast cell-deficient mice infested with Dermacentor variabilis. AB - Acquired resistance to ticks in guinea pigs has been found to be associated with basophil-rich skin reactions. Mice, which are generally believed to possess few, if any basophils, also acquire resistance following repeated tick infestations and this has been found to be associated with increased numbers of dermal mast cells. Mast cell-deficient W/Wv mice have, however, also been shown capable of acquiring resistance after two infestations with Dermacentor variabilis larvae. In the studies described here, we have examined, with the electron microscope, skin reactions in W/Wv and +/+ mice undergoing their third infestation with Dermacentor variabilis. Basophils, along with neutrophils and eosinophils, were identified using established criteria. The possibility that basophils contribute to various pathogenetic mechanisms in these and other strains of mice is discussed. PMID- 2228427 TI - Intestinal mucosal mast cells in Nippostrongylus-infected mice: lack of sensitivity to corticosteroids. AB - Immune reactions to enteric nematodes, in which mast cells are thought to play an important role, are abrogated following corticosteroid treatment of host animals. This is probably due, at least in part, to inhibition of cytokine production by T cells. It has proved difficult to block worm expulsion in mice with corticosteroids. We have therefore examined the effects of corticosteroids on mast cell numbers and concentrations of the mast cell granule-specific serine protease Mouse Intestinal Mast Cell Protease (MIMCP) in the intestines of mice infected with Nippostrongylus brasiliensis. Mucosal mast cell (MMC) numbers and concentrations of MIMCP were unaltered by steroid treatment. This is in marked contrast to Nippostrongylus-infected rats which showed decreases in both mast cell numbers and concentrations of the rat mucosal mast cell protease RMCP II after steroid treatment. This suggests that differentiated murine MMC are less dependent on T cells than those of the rat. PMID- 2228428 TI - Trypanosoma cruzi: calcium ion movement during internalization in host HeLa cells. AB - The role of cytosolic Ca2+ and cytoplasmic calcium movement during the parasitization of HeLa cells by T. cruzi were studied. The level of calcium in parasitized cells increased compared to the control cells. Our experiments demonstrate that this cytosolic calcium originates from the release of the intracellular calcium deposits, especially from the mitochondria of the host cell. The parasitization rates decreased after the cells were treated with drugs to increase the cytosolic Ca2+ levels to inhibit the host-cell calmodulin. PMID- 2228429 TI - Alteration in density of eosinophils in the cerebrospinal fluid of mice infected with Angiostrongylus cantonensis. AB - The density of eosinophils in the cerebrospinal fluid (CSF) and blood of male ddY mice infected with Angiostrongylus cantonensis was examined on days 14, 20 and 27 post-infection (p.i.) with discontinuous Percoll gradient centrifugation. Normal blood eosinophils had a density of between 1.070 and 1.080 g ml-1. No significant changes in density in blood eosinophils were noted during the course of the observations. CSF eosinophils began to become hypodense (defined as density less than 1.070 g ml-1) on day 20 p.i., and 88% of eosinophils were hypodense on day 27. Our results suggest therefore that eosinophils probably become hypodense in the CSF and brain tissues, but not in the blood. PMID- 2228431 TI - Extraintestinal strobilar development of immature Echinococcus multilocularis in laboratory rodents following intratracheal inoculation of the protoscoleces. AB - Intratracheal inoculation of Echinococcus multilocularis protoscoleces was performed in prednisolone tertiary-butylacetate(PTBA)-treated and untreated golden hamsters and AKR/J mice. Repeated PTBA treatments prior to the day of inoculation prevented the influx of neutrophils against the cestode. More than 1 month after infection, living immature adult forms of E. multilocularis, showing some somatic prolongation, were recovered from the pulmonary alveolar space of PTBA-treated golden hamsters, in the absence of any cystic development. PMID- 2228430 TI - Babesia bovis: immunity induced by vaccination with a lipid enriched fraction. AB - A chloroform extract from Babesia bovis-infected erythrocytes was used to vaccinate a group of five naive cattle. Following vaccination, the vaccinates, along with a group of control cattle, were challenged with a virulent heterologous strain of B. bovis. The vaccinates, comparative to the controls, showed delayed as well as decreased parasitaemias. The serological and initial biochemical studies suggested that the immune response was elicited by lipid of babesial origin. PMID- 2228432 TI - Seasonal transmission of Fasciola hepatica in north central Florida (U.S.A.). AB - To assess seasonal transmission of Fasciola hepatica 37 groups of fluke-free tracer sheep, one group of four sheep each month in succession, grazed an infected pasture in north central Florida (U.S.A.) from June 1984 to June 1987. At the end of each month, tracers were moved to a fluke-free barn for 2 months, then necropsied and flukes counted. Fluke transmission mostly occurred during the first half of the year, with peak transmission from February to April. No transmission occurred during the warm summer months, having ceased in either May or June of each year to begin again in late autumn or early winter (November January). PMID- 2228433 TI - The arginine dihydrolase pathway is present in Giardia intestinalis. AB - Growth of Giardia intestinalis in Diamond's TYI-S-33 medium is characterized by a rapid depletion of the arginine in the medium, and concurrent production of ornithine and ammonia. [Guanidino-14C] arginine was converted to 14CO2 by extracts of G. intestinalis suggesting the presence of the arginine dihydrolase pathway. This was confirmed by the detection of arginine deiminase, catabolic ornithine transcarbamylase, carbamate kinase and ornithine decarboxylase in giardial extracts. The findings demonstrate for the first time the existence of the arginine dihydrolase pathway in Giardia, and suggest that arginine metabolism via this pathway plays a significant role in energy metabolism by providing a site for anaerobic substrate level phosphorylation. PMID- 2228434 TI - Does Giardia intestinalis need glucose as an energy source? AB - Giardia intestinalis was grown in Diamond's TYI-S-33 medium containing either 50 mM-glucose or no added glucose to assess its dependence on glucose availability as an energy source. The parameters monitored included cell growth, glucose utilization and the accumulation of end products in the medium. In the medium containing no added glucose, G. intestinalis trophozoites achieved a cell density of about half that of the control, and produced the same end products, alanine, ethanol and acetate. Decreased amounts of both ethanol and alanine were observed (10 and 33% of controls, respectively after 4 days) while there was no change in acetate production. These observations indicate that G. intestinalis can utilize carbon sources other than glucose, and is not absolutely dependent upon glucose as an energy source. PMID- 2228435 TI - Eosinophil responses to Fasciola hepatica in rodents. AB - Qualitative and quantitative cellular changes in the peripheral blood and bone marrow of resistant (rat) and susceptible (mouse) hosts of Fasciola hepatica have been examined. Eosinophil numbers in the peripheral blood and bone marrow of both hosts increased almost immediately following infection. Rats responded more rapidly than mice. Bone marrow colony formation in both rats and mice was greatly enhanced following F. hepatica infection. Injection of excretory/secretory (E/S) antigens of the fluke into rats and mice caused peripheral eosinophilia. Eosinophil levels in mice dropped by day 7 post-injection, but those in rats remained high. Eosinophil precursors in the bone marrow of injected animals also rose. Bone marrow colony formation in antigen-injected mice peaked sharply at day 7 but then fell rapidly. Rats injected with E/S antigens had about twice the level of bone marrow colonies as controls, 12 days post-injection. For most parameters measured, the magnitude of the responses of rats was greater than mice, which may be significant in the context of the rat's ability to acquire resistance to reinfection. PMID- 2228436 TI - The use of computer-aided learning for teaching parasite life cycles. AB - The difficulty of presenting parasite life cycles in a textual or diagrammatic form is discussed and the use of computer-aided learning to solve this is described. The design and use of a Hypercard stack for teaching parasite life cycles on an Apple Macintosh microcomputer are outlined. PMID- 2228437 TI - The concept of truth in psychoanalysis. AB - A philosophical controversy concerning the nature of truth has begun to play an important part in psychoanalytic theorizing. The two major philosophical notions, the coherence and the correspondence theories and their use in psychoanalytic theory making, are examined. It is argued that although coherence is part of the criteria of truth, correspondence is the more essential and fundamental criterion. It was in this way that Freud used these concepts in creating psychoanalysis. Psychoanalytic discoveries concerning the psychogenesis of objectivity in perception and thought support the correspondence theory of truth and provide, in addition, an answer to the third party critique of correspondence. The correspondence theory as a basic attitude of mind is a necessary element in the respect for the patient upon which psychoanalytic therapy depends. PMID- 2228438 TI - As-if: the phenomenon of not learning. AB - In this paper I discuss a clinical problem presented by those patients who, instead of using analysis as an emotional learning experience, invest all their energies in keeping it in a static condition. Using the material of four patients, I illustrate how they have an underlying state of disintegration which is contained in a precarious enclosure. The patients experience great difficulty in facing this situation and preventing further disintegration. I describe a particular type of splitting, which I call 'slicing', by which they achieve an arrest of further disintegrative processes, and for which they need the continuous existence of a useless analysis. I link this situation with Bion's concept of 'minus K'. PMID- 2228439 TI - A hypothesis about the determining process of autistic states. AB - First, the author observes that in the case of autistic children there exists a lack of links with other human beings as such. Instead, intense relationships with objects take place due to the sensory stimuli that they produce. These observations were correlated with ethological studies according to which certain animals, reared far from their fellow-creatures, establish links with other types of objects within their environment, most frequently with the individuals that take care of them or, in the absence of such a person, with a material object. After this link is established, they can stop relating to creatures of the same species. On this basis a hypothesis is elaborated meaning that autistic people would have the instinctive precognition of the creatures of the same species fulfilled not by such creatures (imprinting), but by partial aspects of them, regarding sensory stimuli that they produce. PMID- 2228440 TI - Analysis of a little girl with an autistic syndrome. AB - This paper is a clinical one, relating to a four-year analysis of a 28-month-old girl who developed an autistic syndrome as a reaction to the violent abduction of her parents which she had seen. The reality of the violence of the political situation in the country helped blur the distinction between fantasy and reality for both analyst and patient. The author introduced melodic singing (after the failure of singing with lyrics) as a means of communication with the little girl. Her eventual recovery seems to have been possible because of the soundness of her upbringing during the first two years of her life. PMID- 2228441 TI - Repetition and surprise: a clinical approach to the necessity of construction and its validation. AB - The analysis of a dream revealed, to the surprise of both patient and analyst, identifications corresponding to different times and places. The (re)construction led to the discovery of conflicts involving three generations. We explore the clinical conditions for this discovery, and we develop the links between the concepts of 'historicity' and '(re)construction'. The concept of (re)construction, in its very structure, implies a very fertile paradox: being by definition retroactive, it is at the same time anticipatory, in the sense that it establishes a pre-condition for access to psychical truths. The revelation of unconscious identifications (telescoping of generations) through construction enables the analyst to gain a retroactive understanding of how the patient has understood the interpretations. The analyst obtains thus the means to understand (also in a retroactive way) the value and the limits of his interpretations. PMID- 2228442 TI - On the formulation of interpretations. AB - The author analyses several interpretations published by different authors from the point of view of their linguistic form and the type of language used, in order to determine the therapeutic effect and the manner of working of each. Two types can be distinguished: literal-explanatory language and metaphorical language. Each performs a different function. Metaphorical language is proper to the primary process; it is related to displacement and condensation; it reactivates the most primitive levels of the mind; it serves the purpose of expressing affects and emotions. Literal-explanatory language is proper to the secondary process; it is related to logical-formal thought; it reactivates the most highly developed levels of the mind; it serves a referential, informative and explanatory purpose. A knowledge of the function of each of these forms of language allows the psychoanalyst to direct the interpretations he formulates to either the primary or the secondary process as befits the clinical requirements. PMID- 2228443 TI - Gender and identity issues in the analytic process. AB - The influence of gender--of analyst and analysand--in the unfolding of the analytic process is being addressed. A brief discussion of the reasons why such influence was either dismissed or denied in the analytic literature until recently, is followed by an overview of possible analyst-analysand interactions in the four gender-related dyads. Finally two specific developments, not uncommon in the transference of female patients in analysis with female analysts (and their countertransference implications) are presented. The first refers to the issues around closeness and distance with the maternal object (usually expressed as issues over control and as a sado-masochistic struggle with the analyst in the transference), while the second to the erotization of the transference. PMID- 2228444 TI - The containing function and the analyst's projective identification. AB - The concept of the container and the contained in psychoanalysis describes a process whereby the patient's projective identifications are internalized by the analyst, transformed, given meaning, and returned to the patient in a useful fashion. In this paper, it is suggested that what the analyst gives back, and what the patient receives, is the analyst's projective identification. The containing function itself can be transmitted to the patient via this mechanism. All interpretation, from whatever theoretical viewpoint, has an element of containing and therefore projective identification on the part of the analyst. Paradoxically, neutrality itself can be considered a vehicle for projective identification. Previously, the role of the therapist's projective identification in the containing process has been implied, but not discussed. PMID- 2228445 TI - Catastrophic illness in the analyst and the analyst's emotional reactions to it. AB - The author reviews the fact that there is very little literature available on catastrophic illness in the analyst and the analyst's emotional reactions to it, compared with other topics of interest. Some of the factors suggested to account for this are exhibitionistic concerns, concerns about one's privacy (including psychic privacy), embarrassment related to countertransference, and concerns about losses of referrals if colleagues perceive the analyst to be impaired. The author then draws a distinction between the emotional life of analysts and countertransference, and discusses how and why he defines them differently. The major part of the paper then goes on to discuss two major technical questions in considerable detail: (a) whether or not to give factual information to patients about one's condition, and (b) the manner in which the material is introduced into the analysis. A number of case examples are cited. The author closes with a discussion of the question of the pros and cons of reporting on the experience immediately versus waiting for the passage of time. PMID- 2228447 TI - The investigation of psychoanalytic theory by means of the experimental method. AB - Psychoanalysis has been criticized for its lack of a quantitative research tradition and its resulting reliance on the case history method for its data. While the in-depth observation of a small group of cases has an important place in the development of science, particularly in the hypothesis generating phase, it is argued that the testing of psychoanalytic hypotheses must depend on research methods that allow for more stringent control and replication. Five studies that utilize a true experimental design and that examine psychoanalytically significant topics are described. Special problems confronting the psychoanalytic experimenter are discussed. It is hoped that this article will stimulate those investigators who have an interest in testing psychoanalytic principles to design future studies that are rigorous in their methodology. PMID- 2228446 TI - Post-termination patient-analyst contact: I. Analysts' attitudes and experience; II. Impact on patients. AB - Post-termination patient-analyst review, due to the increased psychological distance from the patient provided by the passage of time, generates an advantaged perspective of the gains and limitations of analytic work than was possible at treatment termination. Despite analysts' widespread belief that such analyst-initiated contact is deleterious to the patient, assessment of clinical experience with such contacts by Luborsky, Martin and Schlessinger, as well as by re-evaluated data of Wallerstein, indicates little or no damage to patients, and in some cases distinct benefits. Analysts generally make post-termination contact with their patients conditional upon the patient's need for additional help, although their personal experience is of unconditional extensive contacts with their own training analyst. Whether expectation of and experience of substantial post-termination contact with the patient's analyst impacts on either the degree of mourning or of resolution of residual transference requires evaluation. PMID- 2228448 TI - A new look at the theory of Melanie Klein. AB - This paper tried to show that Melanie Klein's theory can very profitably be viewed as a descriptive theory of strong emotions rather than an instinct or developmental theory. Furthermore, since in Klein's thinking feelings 'create' objects, the primacy of feelings in this theory is central. The paper contains a short chronological study of Klein's formulations of psychic phenomena in terms of affects. It is also maintained that the paranoid-schizoid and the depressive positions are constellations of affects and of reactions to them; that psychic development is essentially in terms of the capacity to tolerate feelings, and that the basic conflict in mental life is between feelings of love and hate and associated feelings. Such a view solves many of the conceptual difficulties of Kleinian theory and in addition promises rewarding insights into the world of feelings. PMID- 2228449 TI - "A dream is the fulfillment of a wish': traumatic dream, repetition compulsion, and the pleasure principle. AB - This paper describes the case of a battle veteran who suffered from a repetitive traumatic dream and symptoms of a traumatic stress disorder. Psychodynamic exploration revealed the basic wish-fulfilling aspects of both the dream and the fact of its repetition. The patient's obsessional preoccupation with his war experiences was also in significant part determined by unconscious wishes to repeat the infantile experience it represented. It is suggested that the repression of pleasure according to the classic psychoanalytic model is as important a dynamic in the dreams and symptoms associated with specific traumata as with any other neuroses. The question is raised as to whether a repetition compulsion, of normal or pathological intensity, may reflect the wish to repeat a descriptively unconscious pleasurable component of a disturbing experience, as well as to master it. PMID- 2228450 TI - Need for technology assessment in oral health care. PMID- 2228451 TI - Value of technology assessment in developing countries. AB - The contrasting cycles of changing caries prevalence in developing and industrialized countries are described, as they relate to differing needs in technology. Using this contrast as a background, the selective needs for technology in measurement, adequate quality of treatment and materials, appropriate personnel, and simplicity and mobility in equipment are discussed. PMID- 2228452 TI - On amalgam toxicity. PMID- 2228453 TI - Present and future value of dental composite materials and sealants. AB - This article reviews the development, composition, chemistry, recent technological advances, and extent of use of composite resin restorative materials, adhesives, and pit and fissure sealants. The problems related to the clinical behavior of these materials in the oral environment are dealt with, and methods of minimizing their present deficiencies are suggested. Future directions that might be taken to improve these materials and solve some of the inadequacies that these materials exhibit are also discussed. PMID- 2228454 TI - Pit and fissure sealants. An underutilized preventive technology. PMID- 2228455 TI - Long-term assessment of periodontal surgery versus curettage or scaling and root planing. AB - The various treatments for periodontal disease must be assessed in light of the recently articulated goals of periodontal therapy to preserve teeth for a lifetime and to enhance esthetics and comfort as well as oral health. This article examines the long-term comparisons of periodontal surgery, curettage, and scaling and root planing in improving attachment levels instead of the more traditional pocket depth. PMID- 2228456 TI - Rationale for the use of antimicrobial agents in periodontal disease. AB - The traditional approach to treating dental decay and periodontal disease has often focused on caries, neglecting periodontal infection. The past 15 years have seen significant advances in the treatment of periodontal disease with antimicrobial therapy, both with and without more traditional debridement or surgery. This article presents an overview of the use of antimicrobials, including an examination of treatment philosophies and the diagnosis of periodontal infection. PMID- 2228457 TI - Psychological safety of a multiple channel cochlear implant device. Psychological aspects of a clinical trial. AB - Fifty-three deaf patients were screened psychologically and medically for suitability to receive an intracochlear implant. After initial screening for psychological normalcy, candidates were assessed again 1 year postimplant. Isolated deleterious psychological effects were found, and certain aspects of psychological functioning were enhanced. Overall evidence suggests that the implant is not psychologically damaging. PMID- 2228458 TI - Searching for consensus through multi-criteria decision analysis. Assessment of screening strategies for hemoglobinopathies in southeastern France. AB - Until now, no systematic strategy for the prevention of major hemoglobinopathies has been implemented in southeastern France, in spite of frequencies of beta thalassemia trait and HbS trait as high as 2.5-8% in some ethnic populations. The purpose of the study was to help a group of experts, brought together by the Regional Center for Disease Control, to reach a consensus about screening for carriers of heterozygote hemoglobinopathies. A multicriteria decision-analysis model was used to take into account not only the costs and effectiveness of potential screening strategies, but also five other qualitative criteria: technical and practical feasibilities, ethical acceptability, information follow up in time, and global impact on health education. Conclusions differ significantly from those of a pure cost-effectiveness analysis, but a multicriteria approach seems best suited to medical experts' preferences. PMID- 2228459 TI - Format and conduct of consensus development conferences. Multi-nation comparison. AB - The consensus development conference method developed by the National Institutes of Health in the United States has been adopted and modified by a number of countries. Based on published articles and communication with representatives from each country, we examined whether the organization and conduct of these conferences in nine countries (United States, Canada, Denmark, Finland, the Netherlands, Norway, Sweden, Switzerland, and the United Kingdom) enhanced or detracted from achieving the stated conference goals and objectives. We conclude that improvements in the process by which consensus conferences are conducted may be warranted. More scientific methods for synthesizing literature, such as meta analysis, should be used in developing inputs for the conference panel. Formalizing the decision-making processes through polling or other methods that allow for structured disagreement with parts of a consensus statement would potentially expand the range and type of issues that can be addressed in such conferences. Finally, countries should consider having the consensus statement written over a longer period of time than the traditional overnight session, which seems unlikely to promote clear thinking. PMID- 2228460 TI - Analysis of the National Institutes of Health Medicare coverage assessment. AB - The National Institutes of Health (NIH) is periodically asked to conduct assessments of new medical technologies to assist in coverage decisions made at the Office of Health Technology Assessment (OHTA) for the Health Care Financing Administration coverage policy. Analysis of NIH assessments indicates that even though most NIH assessments rely only on expert opinion, OHTA agreed with NIH recommendations in over 90%. PMID- 2228461 TI - Assessment of two oxygen treatment alternatives in the home. PMID- 2228462 TI - Screening with mammography. PMID- 2228463 TI - How ICN is promoting research. AB - "No Health Without Research." That's the conclusion of the 43rd World Health Assembly technical discussions in May and ICN's warning since the early '70s when it began to promote nursing research in earnest. But ICN's commitment to research is not recent. It is deeply embedded in its first constitution in 1900. Below, a review of ICN's special role in supporting research, excerpted from Taka Oguisso's introductory speech to the Task Force on International Research meeting in May (page 287). PMID- 2228464 TI - A survey of nursing research in Nigeria. AB - In Nigeria, nurses are not considered to be sufficiently educated to understand the abc's of research methodology much less to participate in or conduct research. This lamentable fact was made at a conference on "The Role of Research in Nursing" in Nigeria. This was in 1973. Has the situation changed since? For lack of any study or documentation on the topic, and to be able to report on the status of nursing research in Nigeria for the ICN-sponsored Task Force on International Research meeting at end April-May, Rosaline Olade decided to conduct her own exploratory study. While the responses shed light on the situation in both Nigeria and the African region, they also sound only too familiar in countries where nursing is beginning to be recognized at the university level. PMID- 2228465 TI - Nursing in the 21st century in Latin America: Part III--Policies. AB - The following is the last of a three-part analysis of nursing in Latin America. The first two installments dealt with education and practice. Below, a look at current policies and their repercussions for nursing. PMID- 2228466 TI - Nursing regulation moves ahead. AB - Since its creation in 1899, ICN has had a major and legitimate interest in the regulation of the profession. It has supported the passage of appropriate nursing legislation and, through studies, seminars and publications, has consistently sought appropriate and effective regulation. Its strongest effort in this area to date has been "The Nursing Regulation: Moving Ahead" project launched in 1988 with the support of W.K. Kellogg Foundation and other development agencies. And now after 11 workshops involving 77 countries around the world, the project team takes a recapitulating look at the project's evolution and promising outcomes. PMID- 2228467 TI - Nursing in Canada: a profession. AB - The headlines scream out: "Hospitals alarmed as disgruntled nurses flee profession". "Living with death; the strains of daily tragedy feed chronic shortage of nurses". "Ministry should encourage alternative health care". "BC nurses set to withdraw services". As the provincial health care system falters and nurses, the very core of health care, flee the profession, politicians scramble to find answers. And so is Janice Kopinak, who takes a deep look at the current nurses' revolution and sees a glimmer of hope for change. PMID- 2228468 TI - Synthesis: the BSN's preparation for practice. AB - Entry-level competencies and successful role transition have become a major concern of employers, who often complain that new graduates (particularly with baccalaureate degrees) lack preparation for staff nursing. To aid in this transition to the workplace, a clinical course has been developed for the last semester of a BS programme that increases students' confidence and ability to function as competent professional nurses and that could be used by other countries as a role model. Below, a description of the "Synthesis in Nursing Practice" course and its benefits to both students and future employers. PMID- 2228469 TI - Selection and interpretation of laboratory tests for patients with uveitis. PMID- 2228470 TI - Anterior and intermediate uveitis. PMID- 2228471 TI - Fuchs' heterochromic iridocyclitis. PMID- 2228473 TI - Ocular toxoplasmosis. PMID- 2228472 TI - Ocular sarcoidosis. PMID- 2228474 TI - Behcet's disease. PMID- 2228475 TI - Sympathetic ophthalmia and Vogt-Koyanagi-Harada syndrome. PMID- 2228476 TI - Multifocal choroiditis. PMID- 2228478 TI - Brucellosis and nonsyphilitic treponemal uveitis. PMID- 2228477 TI - Lyme uveitis. PMID- 2228479 TI - Fluorescein angiography in patients with posterior uveitis. PMID- 2228480 TI - Immunosuppressive treatment of uveitis. PMID- 2228481 TI - Surgical approaches to uveitis. PMID- 2228482 TI - Peripheral uveitis: an infectious etiology? PMID- 2228483 TI - Group environment and group interaction in psychiatric assessment meetings. AB - This study examines two aspects of psychiatric assessment meetings: staff perceptions of group social climate, and staff verbal interaction. An Experimental group using a novel format was compared with two groups using a Traditional format. Group environment was measured by the Group Environment Scale (GES). Staff verbal interaction was rated both in terms of discussion content and distribution of discussion time among the categories of Chair, Keyworker, and Others. Changes in group environment were found on four out of ten GES subscales: in the Experimental meetings Expressiveness and Independence both increased, while Leader Control, and Anger & Aggression decreased. Content of discussion remained largely unchanged, but there was a marked shift in the distribution of discussion time towards Keyworkers and away from the Chair. PMID- 2228484 TI - Depression and loneliness in overseas students. AB - This paper compared the effect of life change in adjustment of overseas students with those of Australian students. 342 students were divided into 4 experimental groups. There were: Overseas students with residence of less than one year (OV1 group, N = 44), overseas students with residence of more than one year (OV2 group, N = 81), Australian students raised in Brisbane (A3, N = 105) and Australian students raised outside Brisbane (A4, N = 112). The result of discriminate analysis showed that overseas students (OV2) were significantly more likely to experience moderate to severe clinical depression and loneliness than the Australian students. Age and expectation of difficulty in study were the best predictors for depression in overseas students. PMID- 2228485 TI - Evaluation of psychiatric morbidity following an earthquake. AB - Greece has been characterized by high earthquake activity in comparison not only with Mediterranean countries, but also with many parts of Eurasia. In the present study an assessment of the psychiatric morbidity was carried out in the city of Kalamata, Greece, two weeks after the earthquake in September, 1986. A random sample of residents divided into three categories was assessed. The participating groups consisted of 205 adults, 172 high school students and 69 adult outpatients who suffered from minor pathological problems or proceeded for a check-up without being necessarily ill. The Langner and CES-D scales were administered for the population assessment. Detailed statistical analysis revealed that the earthquake had significant psychological effects and caused a considerable degree of depression in all groups. According to the Langner Scale, 31.3% of the general population, 11.6% of the students and 40.6% of the patients exhibited 10 or more symptoms on the Langner scale indicating severe disturbance. Also 50.9% of the whole sample exhibited 6 or more symptoms indicating serious disturbance. In the CES-D scale, 79% of the general population, 69.2% of students and 75% of the outpatients exhibited 16 or more symptoms, or 74.6% of the whole sample. The observed difference between general population and students is significant on Langner scale (p less than 0.001) and on CES-D scale (p less than 0.025). The major symptoms in all groups were prevalence of severe psychiatric symptomatology, anxiety, psychosomatic disorders and depression. PMID- 2228486 TI - Is day hospital treatment effective, and can success be predicted? AB - Clinical improvement is demonstrated in a group of 41 day patients of mixed diagnosis by changes in measures of depression, self-esteem, loquacity and sociability over a period of six weeks. Staff predictions of success, made after 2 weeks, correlated positively (Spearman's rho = 0.53) with an overall assessment of success after 6 weeks, which itself was positively correlated with improvements in scores on depression (rho = 0.58) and sociability (rho = 0.66 and 0.60). The patients for whom staff predicted least success were in 6 cases out of 7 men aged 20-51. PMID- 2228488 TI - Towards culture- and population-specific norms for self-reported depressive symptomatology. AB - This paper: (1) reviewed and integrated the small body of cross-cultural literature on Zung SDS scores among college students and (2) reported new SDS data on students in four countries. Its purpose was to facilitate the development of population- and culture-specific norms for the measurement of depression and to identify patterns in the data available at this time. The results indicated considerable culture and gender specificity. Females had higher SDS scores in all but one group. There was a slight tendency for scores to increase over time. The pattern of mean scores across cultural groups was somewhat inconsistent. Korean and Philippine students had the highest scores, Caucasian Americans the lowest. There was moderate concordance of ranked symptoms across eleven samples. This concordance increased within cultural groups and especially within nations. Finally, two specific methodological problems were discussed. First, nine of ten of the highest ranked symptoms were stated in negative form, which suggests that negative wording biases symptom means. Second, there appear to be additional problems in the specific wording of the libido and diurnal variation items as applied to college students. PMID- 2228487 TI - Problems of meaning in psychiatric screening scales: a critique and possible solutions. AB - It is argued that there are problems in the way that psychiatric screening scales are constructed. The normal procedure is to collect a group of symptom items and sum them creating a single score. While researchers generally assign an equal weight to each symptom, this is not warranted. Using data from two psychiatric screening scales from large representative samples, it is shown that symptoms vary tremendously in the degree to which they are experienced in the population; the more rare symptoms appear to measure depression while the more common symptoms sound much like stress. Summing these items and assigning them equal weights makes little sense, given these differences. Examining case profiles shows that individuals with quite different symptom patterns receive identical scores. Several alternative methods of creating psychiatric screening scales are suggested, including eliminating some items, and devising systems of symptom weights; factor analysis is ruled out, however. PMID- 2228489 TI - Emotional changes in pregnancy and early puerperium among the Yoruba women of Nigeria. AB - A randomly selected clinic population of 400 pregnant women in Ile-Ife, Nigeria, were interviewed for complaints of psychological disorders during the last trimester of pregnancy and the post-partum period. The study shows a considerable degree of psychological disturbances during pregnancy which later decreased significantly during the post-partum. While the complaints of worrying, guilt feeling, nausea and vomiting and "heat in-the-head", were significantly more common in younger women, insomnia and anorexia were more common in older women. The incidence of psychological complaints among the women decreased with increasing parity. There was no significant difference in the incidence between women with monogamous and polygamous marriages. PMID- 2228490 TI - Interaction in health education. AB - The usefulness of the application of the psychodynamic frame of reference in person-to-person health education is examined in the present study. The health educator's proper understanding of his client through an integrative use of his own cognitive and emotional responses to the client is first discussed. Depending on the level of maturity of their personalities, and on the nature of their formative relations, the clients will develop different modes of interaction in their relationships with the health educator. Learning to adequately recognize and meet clients showing different interactional modes is considered to substantially increase the prospects of the health educator helping his clients to accomplish a change in health behaviour. Four levels of interaction and their proper encountering are described and discussed. It is concluded that health education and individual health educators would benefit from an increased familiarity with, and use of, the psychodynamic body of knowledge. PMID- 2228491 TI - Renal cell carcinoma presenting as spontaneous retroperitoneal haemorrhage. AB - On the basis of a spontaneous retroperitoneal haematoma in a 55-year-old female patient the diagnostic and therapeutical problems of such an emergency situation will be discussed. Due to the high incidence of malignant tumours as the bleeding source, radical surgery becomes the necessary treatment, which may be needlessly burdened by high operative risk in the acute phase. For that reason the mode of treatment chosen in this particular case was immediate embolization subsequent to arteriography along with consecutive extracapsular nephrectomy and removal of the haematoma. PMID- 2228492 TI - Universal papillary necrosis: report of a case of widespread sloughed and calcified papillae mimicking multicomponent staghorn calculi. AB - A case of florid papillary necrosis is presented demonstrating the unusual and graphic feature of universal sloughed and calcified papillae, resulting in recurrent obstruction. Recognizing this entity from plain radiographs is important in not overlooking this potentially treatable cause of progressive renal failure. PMID- 2228494 TI - A decade of experience in the surgical treatment of vesicoureteral reflux. AB - Our ten years of experience in the treatment of vesicoureteral reflux is presented. The results have been presented with respect to the grade and the antireflux technique employed, with special emphasis on grade IV and V cases. PMID- 2228493 TI - Treatment of radiolucent renal calculi using ESWL combined with urine alkalinization. AB - During the last 16 months, out of a total of 50 patients with renal urate stones 30 were treated by ESWL alone (Group A) and 20 by ESWL combined with urine alkalinization (Group B) as an adjuvant treatment. The stones were single in 14 cases, multiple in 25 and branching in 11 cases. The average long axis of the stones was 3.6 cm. In Group A 76.6% of the patients were stone-free 3 months after ESWL, in comparison with 90% in Group B patients who underwent the combined treatment. PMID- 2228495 TI - Follow-up of patients treated for urinary bladder calculi. AB - Fifty patients were followed-up for an average of 3 years after treatment for urinary bladder calculi. In 10 of these (20%) altogether 20 metabolic or endocrine diagnoses were revealed at follow-up: hypercalcaemia, 8; hyperuricosaemia, 4; high parathormone, 3; hyperuricosuria, 2; hypercalciuria, 2: hyperoxaluria, 1. About half of the patients also had other diagnoses, dominated by outflow obstruction at the prostatic level, followed by neurogenic bladder disorder. Fifteen had developed new bladder calculi. Urography revealed upper tract calculi in 12 patients, but 11 of these were free from metabolic disorder. Significant bacteriuria was common (24%). Our conclusion is that a follow-up is to be recommended after treatment of bladder calculi. It should include cystoscopy and screening for endocrine/metabolic disorders. PMID- 2228497 TI - Radical prostatectomy and complications. AB - Radical prostatectomy has been successfully applied in the treatment of intracapsular prostatic tumour. A few modifications of the surgical technique are suggested to prevent complications. Initial results confirm that the method works, as all patients have remained continent. One of them died of pulmonary embolism right in the postoperative phase. PMID- 2228496 TI - Combined cisplatin and radiation therapy in patients with invasive bladder cancer. AB - Thirty-five patients with T2-T4 invasive bladder cancer were treated with combined cisplatin and radiation therapy. In 18 patients radical cystectomy was performed after the combined therapy. In the other 17 patients radical cystectomy could not be performed for various reasons. Pathological examination of the cystectomy specimens showed down-staging in 66.7% and no residual tumour in 33.3%. These results suggest a synergistic action of cisplatin and radiation. Side effects were not severe and were well tolerated. This combined therapy of cisplatin and radiation is very effective for invasive bladder cancer. PMID- 2228498 TI - Traumatic rupture of the corpus cavernosum. AB - Penile fracture is a rare entity. Twelve patients with penile fractures were treated surgically with a very low complication rate. Our results were compared with those reported in the literature. PMID- 2228499 TI - Intralbugineous testicular prosthesis, a new technique. Summary of 30 implants. AB - A study of 16 patients who underwent intralbugineous testicular implants during the practice of orchiectomy is presented. In 14 cases of prostatic carcinoma, after bilateral subcapsular orchiectomy intralbugineous prostheses were implanted and in 2 other cases of testicular torsion unilateral prosthesis was implanted. With this new, easily executed technique the size, mobility and testicular sensibility are maintained. PMID- 2228500 TI - Silicon transfer during haemodialysis. AB - Silicon transfers were examined during haemodialysis (HD) in 120 chronic HD patients who received 5-hour dialyses 3 times a week. Si levels were measured by flameless atomic absorption spectrophotometry. Ultrafiltrable Si levels approximately equalled dialysate Si levels. Serum Si levels before HD significantly increased in all patients and total protein values were also high. It is concluded that serum Si levels increasing with time during HD with cellulose acetate or cuprophan is due to haemoconcentration and liberation from the silicon rubber tube. PMID- 2228501 TI - Combined peritoneal and haemodialysis therapy for chronic renal insufficiency. AB - Twenty-three patients with chronic uraemia were treated for an average of 8.5 months with intermittent peritoneal dialysis. When hypervolaemia developed and/or the volume of low-molecular weight substances increased, the therapy was complemented by one or two sessions of haemodialysis per week. The combined treatment was carried on for 4.1 months on average, in consequence of which the general condition improved, body weight reached the optimum, blood pressure diminished, turned normal and could be controlled by drugs. In the wake of the therapy carbamide nitrogen and creatinine levels dropped significantly, serum total protein and albumin values increased. At the close of the observation period 3 patients remained under combined therapy, 2 had undergone cadaveric kidney transplantation, 18 were transferred to chronic haemodialysis. Thoughts are evolved about the advisability of intermittent peritoneal dialysis and combined therapy in the care for uraemic patients. PMID- 2228502 TI - Urinary tract infections in post-renal transplant patients. AB - The overall incidence of urinary tract infections (UTIs) in our renal transplant population was 30.9%, i.e. 0.15 episode per patient-year. UTIs occurred more often within the first 3 months (60%) of transplantation. Fifty per cent of UTIs were asymptomatic. Recurrences were common. Acute tubular necrosis and cellular rejections were important associations. UTIs had little effect on graft function and survival up to 3 years post-transplant. PMID- 2228503 TI - Serum selenium levels in healthy adults and its changes in chronic renal failure. AB - In this study the serum selenium levels of 500 healthy Greeks and 225 patients with chronic renal failure (CRF) were measured using Watkinson's method. The patients were treated either conservatively or by peritoneal dialysis or haemodialysis. We found that the levels were in an intermediate position compared to those of other Europeans. Selenium levels were also found to increase significantly with age. No difference was detected between male and female patients. A statistically significant drop was observed in CRF patients compared to age matched controls. This drop was smaller in patients treated conservatively than in those treated by peritoneal dialysis. A further drop was observed in patients under haemodialysis. PMID- 2228504 TI - [Continuing education. Changes in late ventricular potentials in the ECG]. PMID- 2228506 TI - [Paraneoplastic syndromes in dermatology. Cutaneous paraneoplasias]. PMID- 2228505 TI - [Paraneoplastic endocrinopathies]. PMID- 2228507 TI - [Paraneoplastic myopathies]. PMID- 2228508 TI - [Paraneoplastic syndromes of the hematopoietic cell system]. PMID- 2228509 TI - [Paraneoplastic disorders of hemostasis]. PMID- 2228510 TI - [Fever, weight loss and rare paraneoplasias]. PMID- 2228511 TI - [Fatigue, pulmonary coin lesions and liver tumor]. PMID- 2228512 TI - [Bronchial asthma, eosinophilia and vasculitis]. PMID- 2228513 TI - [Nicotine patch for smoking cessation?]. PMID- 2228514 TI - Characterization of the tumorigenic and metastatic potential of a poorly differentiated human colon cancer cell line. AB - We characterized the tumorigenic and metastatic potential of a poorly differentiated, non-CEA-producing colon cancer cell line, MIP-101, after injection at different sites in athymic mice. After subcutaneous and intrasplenic injection tumor grew locally in 100 and 50%, respectively, but no metastases were found, even after intravenous injection. Intraperitoneal implantation, however, resulted in a high tumor take (10/10) and subsequent liver colonization (8/10 mice). Exogenous CEA prior to intrasplenic injection induced metastasis in 7/8 mice (in 2 mice to the liver and in 5 mice to the lung). Intrasplenic injection of CX-1, a good CEA producer, resulted in hepatic metastases in 100% of the animals. These data suggest a direct or indirect role of CEA in the metastatic process. We conclude that MIP-101 has a high tumorigenic and invasive potential but a low metastatic proclivity, except when grown in the peritoneum, and that pretreatment of tumor-bearing animals with CEA affects the metastatic proclivity. PMID- 2228515 TI - Intrapulmonary spread of established B16 melanoma lung metastases and lung colonies. AB - Spontaneous metastasis of subcutaneous B16 melanoma transplants proceeds in two distinct stages: initially to the lungs, and secondarily, following tumor removal, from established lung metastases to extrapulmonary systemic sites. Coincident with extrapulmonary metastasis, there is a dramatic amplification of visible lung metastases, with death generally resulting from extensive lung metastasis. The progression of lung metastasis, and lung colonization initiated by intravenous injection of tumor cells, was investigated using B16 melanoma clone G3.12. Analysis of the growth of invisible metastases in organ culture explants of lung revealed that tumors continually disseminated relatively small numbers of lung metastases after reaching a size of about 6 mm in diameter. However, most terminal-stage lung metastases, along with all extrapulmonary metastases, apparently arise from a secondary spread of tumor cells from tumor derived lung metastases 1-2 mm in size. Individual lung colonies, initiated with G3.12 cells bound to single microbeads, also disseminated large numbers of secondary lung colonies, as well as extrapulmonary colonies, at a 1- to 2-mm size. The mechanism for intrapulmonary spread of secondary metastases and colonies is unclear, but the consequence appears to be a secondary stage of intrapulmonary and extrapulmonary metastasis with selection for tumor cells with rapid growth rates. PMID- 2228517 TI - Change in the role of the spleen from protective to harmful following tumor progression in AKR lymphoma. AB - Tumor progression has been reported to be often accompanied by a loss of sensitivity to various elements of the immune system. In the present study, three variants of malignancy of AKR lymphoma were compared as to the host reaction they elicit. Splenectomy caused an acceleration of growth of the low-metastasizing tumor, slightly inhibited the growth of the tumor of intermediate malignancy and significantly inhibited the development of the high-metastasizing lymphoma. These results suggest that splenic elements exert an inhibitory effect on the low metastasizing tumor and a growth-stimulatory effect on the more malignant ones. While decreased sensitivity to various host defense mechanisms following tumor progression has been amply documented, the present study shows a more severe phenomenon: increased malignancy can be accompanied by a deviation of the host immune reaction from tumor growth inhibition to growth stimulation. PMID- 2228516 TI - Lymphatic metastases from the peritoneal cavity are increased in the postinflammatory state. AB - Cell suspensions of chemically induced tumors (rhabdomyosarcoma) were transplanted into the peritoneal cavities of Lewis rats. In normal animals, the greater omentum was the main site of tumor growth, and transdiaphragmatic metastases to regional lymph nodes in the mediastinum were few and small. In animals during the healing phase of a chemical peritonitis, the greater omentum was fibrotic, shrunken, and inactivated. The loss of the scavenging function of the omentum was associated with wide dissemination of the tumor in the peritoneal cavity and increased access of the tumor to the lymphatic stomata on the peritoneal surface of the diaphragm. Number and size of transdiaphragmatic metastases in draining lymph nodes were greatly increased in this postinflammatory state. PMID- 2228518 TI - Interactions of exogenous heparan sulfate with tumor cells of different metastatic phenotype. AB - Heparan sulfate (HS) enhanced the growth of the highly metastatic (HM) 3LL cell line, but not that of the low metastatic (LM) counterpart, in a dose-dependent way. Heparin, chondroitin sulfate, hyaluronate did not produce this effect. At 4 degrees C both cell lines exhibited high affinity binding sites (Kd 10(-8) M) for exogenous HS. Unlike LM cells, the HM ones lost half of the surface-bound HS during the 24-hour incubation at 37 degrees C. HM cells in the exponential growth phase took up the bound HS at lower rate than the LM counterparts. Both cell lines fragmented the exogenous HS intracellularly, but only the HM cells were able to degrade it at the cell surface. The HM cells contained much more heparin binding proteins--especially in the cell membrane and nuclear fraction--than the LM ones. These results clearly demonstrate that the interactions of tumor cells with exogenous HS are influenced by the invasive phenotype. We suggest also that there could be a correlation between the surface degradation, the slow uptake and the growth-promoting effect of the exogenous HS. PMID- 2228519 TI - Substance abuse: a problem that won't go away. PMID- 2228520 TI - The price of addiction. PMID- 2228521 TI - Babies at risk: drug abuse and pregnancy. PMID- 2228522 TI - The case of the pained hypertensive. PMID- 2228523 TI - Medicus, physicus, doctore. PMID- 2228524 TI - IFMC case notes. Private review. PMID- 2228525 TI - Governor's alliance on substance abuse. PMID- 2228526 TI - Molecular biology of cancer. PMID- 2228527 TI - The use of cyclosporin A in adult nephrotic syndrome: nine cases and literature review. AB - Nine adult patients with resistant nephrotic syndrome were treated with cyclosporin A (CyA). All had failed to respond to high dose corticosteroids with or without cyclophosphamide. Three patients had minimal change disease, 3 had focal sclerosing glomerulosclerosis (FSGS), 2 had mesangiocapillary GN, and one had membranous nephropathy. The mean age of the patients was 26.4 years (range 16 to 39 years). CyA was given orally twice daily at a mean dose of 6.7 mg/kg/24 hours (range 6-10 mg/kg/24 hours). Four patients achieved full remission, two patients went into partial remission and three failed to respond. Two patients developed clinical nephrotoxicity, which reversed on dose reduction or cessation of CyA. All 3 patients with minimal change disease who responded subsequently relapsed after stopping CyA, but remitted rapidly on reintroduction of the drug. We suggest that the mode of action of CyA in nephrotic syndrome may be related to intra-renal vasoconstriction in addition to its direct immunosuppressive effect. In this limited series, we found that CyA can be an effective therapy for otherwise refractory nephrotic syndrome, although relapse on withdrawal of CyA may well be a significant clinical problem. PMID- 2228528 TI - The use of the laryngeal mask airway in day case and short stay surgery. AB - An increase in day case surgery has followed a reduction in the number of hospital beds available. Anaesthetic methods and techniques must be modified so that patients can be safely discharged as soon as possible following surgery. The use of Brain's laryngeal mask airway (L.M.A.) can play a part in achieving this objective. PMID- 2228529 TI - Regular planned respite admissions to a geriatric unit. AB - A programme of regular planned respite admissions to the geriatric unit in Cork was established in 1984, for dependent elderly being cared for at home. Retrospective analysis of the respite programme sought to establish its bed utilisation, type of patients admitted, factors in their selection process, their outcome and any associated hospital morbidity. Twenty-four patients have used the scheme during the four years since its commencement, with an efficiency of bed utilisation in 1987 of 14 patients occupying a mean of 4.33 beds per month. The median number of medical problems per patients was five; their median age 77 years and the percentage over 80 years was 46%. Twenty-two patients were already receiving intensive rehabilitation before being placed on the programme, mobility problems dominated. Nine patients continue on the programme with a mean of 23.9 months of respites to date, eight were discharged and seven died. There was no significant difference between the number of respite stays in hospital and "at home" stays complicated by morbidity. The results suggest that even for a highly selected group of dependent elderly, a planned programme of respite admissions is an effective form of care, uses hospital beds efficiently without associated morbidity and may provide an alternative to long stay institutional care. PMID- 2228530 TI - Surgical management of gastric cancer. AB - The presentation and surgical management of gastric cancer is changing as a result of advances in endoscopy and preoperative imaging techniques. One surgeon's experience with 44 cases operated on between 1982 and 1988 is reviewed. Endoscopy was performed in 93% of cases. A sub-total gastrectomy was performed in 23 cases, a total gastrectomy in 13, and a proximal gastrectomy in eight. Of the cancers, 13 involved local or distant structures (d+), 18 had lymph node involvement (+) and 13 were node free (-). Of the first 22 patients, only four had a node (-) lesion compared to nine of the second 22 patients (p = ns). There were two postoperative deaths (4.5%) and eight postoperative complications (20%). Mean hospital stay for (d+) patients (36.2 +/- 22.8 days) was significantly longer than that of the node (-) group (18.3 +/- 5.7 days) (p less than 0.02). Over half the (d+) group died within six months and survival was significantly worse than in the node (-) group for the following three years. No patient in the node (-) group has developed recurrent carcinoma after a mean follow up of 21 months (6 months - 4 years). Early results suggest that subtotal gastrectomy is curative in node (-) patients. Extensive gastrectomies may not be justified in patients with advanced gastric cancer if symptoms do not warrant it, as hospital stay is likely to be prolonged and long term survival is poor. PMID- 2228531 TI - Lung pathology in HIV positive patients. AB - We describe the results of 43 bronchoscopic examinations carried out on 35 patients who were HIV positive. Of these, 13 were intravenous drug abusers, 13 were homosexual or bisexual, six were haemophiliacs, two were homosexual intravenous drug abusers and one was a heterosexual contact of a drug abuser. All underwent investigation because of respiratory symptoms. Aetiological diagnosis could not be made from physical examination, x-ray or routine laboratory tests but, was usually made using bronchoscopy and its associated investigations. Using these techniques, Pneumocystis carinii pneumonia was the commonest diagnosis (19 cases) followed by bacterial infection. Mycobacterial infection accounted for two cases and non-specific interstitial pneumonitis accounted for three. Kaposi's sarcoma was found in one instance and eight investigations were non-diagnostic. PMID- 2228532 TI - Raised PPD antibodies in active pulmonary tuberculosis. AB - Antibodies to purified protein derivative of tuberculin (PPD) were measured in 47 patients with active pulmonary tuberculosis and in various control subjects using an enzyme linked immunosorbent assay. Raised IgG anti PPD antibodies were found in 30 patients with active tuberculosis, in one of 28 patients with miscellaneous non tuberculous diseases and in one of 49 healthy control subjects. This gave the assay a sensitivity of 65% and a specificity of 98%. Antibodies were also measured in a further 20 patients with suspected tuberculosis but in whom microbiological evidence was absent. In eight of these patients active tuberculous disease was subsequently validated on the basis of clinical response to chemotherapy: raised PPD antibodies were found in six of this group but in none of the remaining 12 patients in whom the diagnosis of tuberculosis was considered doubtful. Further studies showed that patients' PPD antibody level fell over a one year period of successful therapy and that tuberculin skin testing and BCG vaccination did not cause a rise in antibodies in healthy subjects. These results suggest that the measurement of PPD antibodies is a useful adjunctive test in the diagnosis of tuberculosis. PMID- 2228533 TI - Metastatic malignant melanoma in pregnancy. AB - A 29 year old expectant mother was critically ill at 27 weeks gestation with disseminated metastatic malignant melanoma and was treated with dacarbazine. A dramatic remission was induced and at 38 weeks gestation she went into labour spontaneously and delivered a healthy infant. She relapsed and died eight weeks post partum. This is the first reported use of dacarbazine in pregnancy. PMID- 2228534 TI - Seal finger in a wildlife ranger. AB - We describe a case of septic arthritis of the interphalangeal joint of the thumb in a man following a seal bite. Early and continued treatment with antibiotics of the penicillin family failed to control the infection. Empirical treatment with tetracycline resolved the infection, but the patient has permanent joint damage. In apparently ordinary infective conditions, which fail to respond to therapy, the history may suggest that an unusual organism is responsible. PMID- 2228536 TI - Septicaemia and the prevention of multiorgan failure--the intensive care perspective. AB - Septicaemia frequently presents without "classic" signs of infection--tachypnoea, hypotension and confusion are the commonest features. The mortality rate is 40 to 80% and in intensive care units, septicaemia accounts for 70% of all deaths. Despite the use of antimicrobial drugs to which the offending organism is sensitive, patients are still dying. Effects on distant organ systems are due to "Mediators". "Microvascular Failure" resulting in tissue hypoxia is the unifying hypothesis of multiple organ failure in septicaemia. Mortality is correlated with the number of organ system failures. Supportive management is aimed at prevention of organ failure--manipulation of the circulation being the central key. Intravascular volume expansion, vasoactive drugs, mechanical ventilation and invasive monitoring are the means. Antimicrobial therapy must be guided by 'best guess' approach with multiple agents until isolation of the offending organism can recommend specific therapy. Aggressive surgical drainage or excision, is particularly applicable in abdominal sepsis. Several adjunctive therapies aimed at mediators of sepsis, are as yet experimental. PMID- 2228535 TI - Resuscitation skills among the general public in Dublin. AB - Evidence exists that many of the victims of cardiac arrest due to ischemic heart disease can be resuscitated if cardiopulmonary resuscitation (CPR) and defibrillation are made available in the minutes following collapse. In order to evaluate the ability of the general public in Dublin to perform CPR appropriately, 225 people were asked when CPR was indicated and how cardiac arrest was diagnosed and then asked to perform CPR on a mannequin. In the knowledge sections, 45% gave an appropriate indication for CPR and 34% gave appropriate criteria for diagnosing cardiac arrest. However, only eight participants were able to perform CPR correctly and only six (2.6%) had both the correct skills and knowledge. There is an urgent need to improve the public's knowledge of and ability to perform CPR as part of an overall strategy to decrease mortality from ischemic heart disease in Ireland. PMID- 2228538 TI - Current management of gall stones. PMID- 2228537 TI - Exercised induced migraine. PMID- 2228540 TI - Epilepsy and the European dimension. PMID- 2228539 TI - Ulcerative colitis relapse: a continuing enigma. PMID- 2228541 TI - Breast enlargement in infants and children. PMID- 2228542 TI - The Ugandan AIDS epidemic--a personal comment. PMID- 2228543 TI - Blood pressure levels among primary school children. AB - Blood pressure, height, weight and body mass index were measured in 1,280 Irish children aged 5-12 years (640 boys and 640 girls). Mean systolic and diastolic pressures accurate to within +/- 3 mmHg for each one year age-sex-group are presented. Blood pressure levels were found to correlate positively and significantly with height, weight and body mass index in both sexes. Forty nine (8%) boys and 58 (9%) girls were found to have a mean systolic blood pressure level above the 95th percentile value recommended by the 1987 Task Force of the National Heart Lung and Blood Institute of America. Sixty eight (11%) boys and 71 (11%) girls had elevated diastolic levels above 95th percentile values, while 19 (3%) boys and 20 (3%) girls had an elevation of both systolic and diastolic pressure. The implications of these findings for Irish children are discussed. PMID- 2228544 TI - An evaluation of an anticoagulant clinic. AB - Patient comprehension of the risks of anticoagulation, tablet recognition skills and knowledge of complications of warfarin therapy were evaluated in 160 patients attending the anticoagulant clinic in a central Dublin teaching hospital group. Potential complications from over- and under- dosage with warfarin were unknown to 119 (74%) and 97 (60%) patients respectively. 1, 3 and 5 mg tablets could not be identified by 40 (25%), 55 (34%) and 60 (37%) patients respectively. The current prescribed dose could not be recollected by 31 (19%) patients. Haemorrhagic complications occurred in 23 (14%) subjects over one year, four of whom required hospital admission and two blood transfusions. No thromboembolic episodes were noted. This study reveals a widespread lack of understanding of anticoagulation and its potential complications in patients receiving warfarin therapy and has led to a critical reappraisal of patient education, patterns of referral and supervision of such individuals in our clinic. PMID- 2228545 TI - Physical signs: papilloedema. PMID- 2228546 TI - Contact sports and injury. AB - A year long survey of sports injuries in the accident and emergency department of St. Luke's Hospital, Kilkenny revealed 864 injuries, with hurling and soccer accounting for 41% and 23% respectively. In hurling, lacerations to face and scalp, and fractures of the wrist and hand, accounted for a large number of the injuries seen, while in soccer bruising and sprains of the lower limbs accounted for the majority of the injuries. We make some recommendations for avoidance of these injuries. We show clearly that non-accidental or deliberately inflicted injury forms a significant proportion of sport injuries and recommended steps to curb non-accidental injuries. PMID- 2228547 TI - Abuse versus neglect: a model to understand the causes of and treatment strategies for mistreatment of older persons. PMID- 2228548 TI - How can we best care for persons who are medically indigent in a world of limited resources? PMID- 2228549 TI - Johnson v. Gross. PMID- 2228550 TI - In re Gannon ex rel. Coons. PMID- 2228551 TI - Couture v. Couture. PMID- 2228553 TI - The hormonal regulation of purine nucleotide turnover. Influence of testosterone in rat liver. AB - An influence of testosterone on de novo purine nucleotide synthesis has been demonstrated in rat liver of adult and prepubertal castrated rats, showing that the action of the hormone is not limited to sexual organs. Castration accelerated the turnover of purine nucleotides in adults rats and reduced it in prepubertal castrated rats. Administration of testosterone tended to restore normality in both cases with opposite mechanisms, lowering the reaction rates in the first group, enhancing them in the second one. An action of the hormone on the inosinic branch-point and specifically on GMP synthesis, was evident, which was again different according to the age of the animal. The observed changes in purine nucleotide metabolism could be responsible for variations in RNA and DNA metabolism, in cellular size and number--which probably occur in the liver--after orchiectomy and following androgen administration. PMID- 2228552 TI - Tryptophan, copper and zinc in hair of healthy subjects. Correlation with differences in hair pigmentation. AB - Tryptophan, copper and zinc levels were determined in the hair of 300 healthy subjects divided by sex, age and hair colour. Sex influences tryptophan content in hair, the levels of this amino acid being higher in males than in females. Tryptophan is also higher in infancy (2-5 years) and in both males and females aging around 80 years and over. Hair colour also influences tryptophan levels, which increase from fair to black hair. Copper levels are similar in hair of both males and females, while those of zinc are higher in women. Age influences the distribution of these two metals in human hair. Copper contents in hair of males are higher at the age 20-40 years. In females, values decrease over the age of 60 years. Instead, zinc levels are higher between 20 and 60 years in males, and between 13 and 19 years in females. As regards hair colour, copper is slightly higher in black hair in males and in fair hair in females, and lower in white hair in both sexes. Zinc values appear to be higher in red and lower in white hair in males. In females they are higher in black hair. PMID- 2228554 TI - Primary structure of rat liver L-threonine deaminase. AB - The primary structure of rat liver L-threonine deaminase has been studied utilizing a highly purified preparation (S.A. = 940 U/mg protein) obtained from Wistar male rats. These data have been compared with the predicted sequences obtained by other Authors, showing a considerable concordance with the Noda's prediction and difference with the Ogawa's results. The FAB-MS analysis has demonstrated the presence of an acetyl group as blocking agent on the N-terminal alanine. PMID- 2228556 TI - The antitumor action of seminal ribonuclease tested with the plasmacytoma spleen colonization assay. AB - The antitumor action of bovine seminal ribonuclease was evaluated with a quantitative assay based on the production of tumor foci in the spleens of mice injected with plasmacytoma cells. The antitumor action depended on the integrity of the catalytic site, and on the dimeric structure of the enzyme. A working hypothesis is proposed, based on these results, and on previous results obtained studying the antitumor action of seminal RNAase in vitro on cell cultures. According to this hypothesis, the antitumor action is based on the ability of seminal RNAase to interact at specific receptor sites on the tumor cell membrane, as well as on its RNA degrading ability. PMID- 2228555 TI - Amino acid sequence around the pyridoxal 5'-phosphate binding site of rat liver L threonine deaminase. AB - Rat liver L-threonine deaminase is a pyridoxal 5'-phosphate dependent enzyme. In the present study we have studied the amino acid sequence composition of the peptide surrounding the coenzyme binding lysine at the active site of the native enzyme. We have also examined the homology between this peptide and the analogue forms of L-threonine deaminase from different sources. PMID- 2228557 TI - Family medicine--an overview. PMID- 2228558 TI - Cutaneous leishmaniasis serodiagnosis by immunoperoxidase assay. AB - Immunoperoxidase assay was used for the determination of serum-specific anti leishmanial IgG antibodies in 65 patients with cutaneous leishmaniasis (CL), in 5 with visceral leishmaniasis (VL) and in 84 controls. A significant difference was observed between CL and VL sera and the control sera when either Leishmania major, L. donovani or L. aethiopica intact promastigotes were used as antigens. CL patients showed similar activity against L. major and L. donovani antigen (titers 4-64 and less than 2-64 respectively), whereas VL patients showed a higher activity with the homologous antigen L. donovani (titers 128-2,048). A high and significant correlation was demonstrated between immunoperoxidase assay, immunofluorescent assay and radioimmunoassay. No cross-reactivity was found with sera from malaria patients. PMID- 2228559 TI - Oxygen free radical scavenger system intermediates in essential hypertensive patients before and immediately after sublingual captopril administration. AB - Oxygen-free radical intermediates/scavengers were measured in 43 patients with essential hypertension who, although under antihypertensive therapy (without angiotensin-converting enzyme inhibitors), still had high blood pressure values. Measurements were taken before and 30, 60 and 120 min after sublingual administration of 25 mg captopril. Both systolic and diastolic blood pressures were reduced significantly. Twenty normotensive healthy volunteers were used as controls. The hypertensive patients had lower glutathione peroxide activity (GSHPx), higher superoxide dismutase (SOD) and serum glutathione reductase activity (GSHRx) compared with the controls. After captopril (30, 60 min) the glutathione and GSHPx increased compared with the pretreatment values. SOD and GSHRx remained high compared with the controls, while whole blood glucose-6 phosphate dehydrogenase remained low. Another group of 19 essential hypertensive patients, free of any antihypertensive medication (for at least 3 weeks), had lower GSHPx, SOD and higher GSHRx than the normal control group. Our results show significant differences in the oxygen free radical scavenger system of hypertensives compared with the normal subjects. It may be that captopril has a concomitant scavenging action together with its antihypertensive effect. Our study raises the question whether cell/organ damage will occur in hypertensive patients exposed to oxidative stress during periods of low antioxidative capacity. PMID- 2228560 TI - Prevalence of thyroid disorders among the elderly in Israel. AB - The prevalence of thyroid disorders was investigated in 698 elderly people (443 women and 255 men), registered in special family health clinics of the Israel Ministry of Health and in two homes for the aged. The first screening was done by serum thyroxine (total T4) examination, and those with values greater than 150 nmol/l or less than 64 nomol/l underwent further laboratory and clinical evaluation in our endocrinological service. Hypothyroidism was diagnosed in 12 women and 5 men (2.5% of the cohort) and hyperthyroidism in 10 women and 1 man (1.5% of the cohort); thus the prevalence of thyroid disorders among the elderly was 4% in this population. PMID- 2228561 TI - Aquagenic pruritus: prevalence and clinical characteristics. AB - We conducted a study of the prevalence and clinical characteristics of aquagenic pruritus (AP) in 996 employees at a general hospital. Forty-five of them claimed that they had AP, thus giving a reported prevalence of 4.5%; 12 were excluded for various reasons and a detailed workup was carried out in 33 people. In more than 75% of the cases AP had started before age 30 and lasted for over 10 years in 42%. The onset of AP occurred within 5 min of exposure in 76% of the cases and usually lasted between 10 and 30 min. In most cases no association could be demonstrated between AP and each of the following factors: place, season, time of day, water temperature, type of soap, towelling or mental stress. AP in at least one other family member was found in 33% of the cases. PMID- 2228562 TI - Carnitine palmitoyltransferase deficiency: a common cause of recurrent myoglobinuria. AB - Six patients with carnitine palmitoyltransferase (CPT) deficiency were diagnosed. Five were males aged 12-48 years and one was a 7-year-old girl. Severe myoglobinuria with renal shut-down led to the diagnosis in four, the main cause of myoglobinuria being prolonged exertion. Other precipitating factors included febrile illnesses, fasting and sleep deprivation. Between attacks, EMG, serum creatine kinase (CK) activity and the response of serum lactate to ischemic exercise were normal in all patients. The diagnosis of CPT deficiency was based on assay of the enzyme by the isotope exchange assay in leukocyte, muscle or cultured skin fibroblast homogenates. CPT activity assayed by the forward assay under standard conditions was normal. CPT deficiency seems to be a common cause of exercise-induced myoglobinuria. Prompt diagnosis can lead to avoidance of risk factors and prevention of rhabdomyolysis and its consequences. PMID- 2228563 TI - Screening for thyroid disease. PMID- 2228564 TI - Acquired von Willebrand's disease, plasma cell dyscrasia, and angiodysplasia: more than a coincidence? PMID- 2228565 TI - Pregnancy and cavernous sinus involvement in a patient with primary non-Hodgkin's lymphoma of bone. PMID- 2228566 TI - Electrocardiographic classification of acute myocardial ischemia. PMID- 2228567 TI - Inhibition of polyamine synthesis suppresses human lymphocyte proliferation without decreasing cytokine production or interleukin 2 receptor expression. AB - Difluoromethylornithine (DFMO) irreversibly inhibits ornithine decarboxylase (ODC), a crucial enzyme in polyamine synthesis, and impairs mitogen-induced lymphocyte proliferation. To examine the mechanism of action of DFMO, we studied the effect of this ODC inhibitor on lymphokine production and interleukin 2 (IL 2) receptor expression. DFMO decreased thymidine uptake of peripheral blood mononuclear cells stimulated by the mitogens phytohemagglutinin, concanavalin A, phorbol myristate acetate and ionomycin 60-70% compared with untreated cells, and the inhibition could be completely reversed by 10 mM spermidine. DFMO had no effect on IL 1 production by monocytes exposed to silica particles. Concentrations of IL 2 increased 7-fold in DFMO-treated, PHA-stimulated PBMC cultures, compared with untreated cells; whereas IL 2 receptor expression as measured by the anti-Tac monoclonal antibody was not affected by the inhibition of ODC. Mixing experiments using cells cultured with or without DFMO indicated that the inhibition by DFMO was not mediated by suppressor cells. Our results strongly support the concept that polyamines are required for a relatively late event in lymphocyte activation occurring after the interaction of IL 2 and its receptor. PMID- 2228569 TI - Matching client and therapist ethnicity, language, and gender: a review of research. AB - The purpose of this article is to examine whether therapy process and outcome are influenced by a client-therapist ethnicity, language, or gender match. A review of research in this area does not demonstrate support for a client-therapist match on any of these variables. The methodological problems and unresolved conceptual issues involved in this research may limit the findings. The ethical and political context of the research and the implications for mental health nursing are explored. PMID- 2228568 TI - Alleviation of experimental cyclosporin A toxicity by substitution of fish muscle oil as drug vehicle. AB - The toxicity of cyclosporin A (CsA) formulated in either olive oil (OO) or fish muscle oil (FO) was investigated in groups of normal Sprague-Dawley rats or in animals which had undergone laparotomy or unilateral nephrectomy. CsA (25 mg/kg/day for 14 days) was administered by gavage from the time of operation, and indices of renal and hepatic function were determined at regular intervals. Urinary thromboxane B2 (TxB2) excretion and whole blood CsA concentrations were determined on day 14, when renal histology was also examined. Compared to CsA/OO treatment, and observed only in normal animals, body weight was significantly increased following administration of CsA/FO, to values similar to those observed following treatment with FO alone. Although there was evidence of renal dysfunction in all CsA-treated animals, irrespective of drug vehicle, elevations in plasma urea and urinary N-acetyl-beta-D-glucosaminidase activity were significantly more pronounced in rats given CsA/OO compared with CsA/FO. Indeed, compared with pretreatment values, no significant changes in these parameters were observed in CsA/FO-treated nephrectomized animals. Whilst there were no great differences in plasma creatinine or creatinine clearance rates between CsA/OO- and CsA/FO-treated groups, animals given CsA/FO showed less evidence of renal structural change as assessed by proximal tubular cell vacuolation, basophilia and microcalcification. The extent of hepatic impairment was also significantly less pronounced when FO was used as drug vehicle. Groups of CsA/FO treated animals also demonstrated significantly lower whole blood CsA levels compared with CsA/OO groups; moreover, TxB2 excretion was significantly lower in the former group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228571 TI - Retirement: what happens to the marriage. AB - The focus of this descriptive study was to examine what happens to the marriage at retirement. The data were to serve as a basis for further investigation toward the creation of a marital enhancement program at retirement. Purposeful sampling was used to identify the 10 couples who were involved in the study. Findings from this study indicated that an effective marital enhancement program at retirement would consider the following factors: changes in roles and identity were significant stressors during this time; the communication of thoughts was more frequent than the communication of feelings; spouses became increasingly aware of their partners' faults during retirement; men appeared to be more satisfied in retirement than their wives; hobbies and time spent together did not change following retirement; children served as important topics of conversation and sources of pride and thought; time spent with children following retirement did not increase; and children were often unaware of the challenges and changes faced by their parents at retirement. PMID- 2228570 TI - Enhancing the self-esteem of inpatient alcoholics. AB - This study examined the effect of pairing inpatient alcoholics with nursing home residents (NHRs) on the alcoholics' self-esteem. In this PALS program, the alcoholic inpatients assumed a helping-companion relationship with the NHRs for 2 hr per day during their last 2 weeks of treatment. Fifty alcoholic inpatients were randomly assigned to the PALS program (n = 25) or to the library for free reading time (n = 25). The Tennessee Self-Concept Scale (TSCS) was administered to all subjects in both groups before and after the interventions. Of the nine TSCS scales, the improvement on the Moral-Ethical scale was significantly greater in the PALS group. Because the alcoholic inpatients in the PALS group engaged in altruistic (moral) behavior, this study provides a logical link between the intervention and the outcome, which has been a prevalent weakness in previous studies of self-esteem in alcoholics. PMID- 2228572 TI - Behavioral competence as a predictor of perceived control in nursing home elders. AB - The purpose of this study was to describe the relationship between behavioral competence and perceived control in nursing home elders. The literature strongly supports perceived control as a primary determinant of psychological well-being in nursing home residents. Identifying predictors of this salient variable will enhance the development of interventions to increase and maintain control in nursing home elders. A nonrandom sample of 134 cognitively intact nursing home elders with poor to excellent self-rated physical health was selected from 13 nursing homes in four counties of a southeastern state. Instruments used included the Desired Control Measure and the Philadelphia Geriatric Center Multilevel Assessment Instrument. Regression analysis demonstrated that components of behavioral competence, time use and self-rated health, explained 34% of the variance of perceived control. Additional research questions were identified. PMID- 2228573 TI - Facilitating growth and development: a paradigm case for modeling and role modeling. AB - This article describes an example of a paradigm case for the nursing theory of modeling and role-modeling. A synthesis of the mid-range theoretical linkages of basic need satisfaction, object attachment, and growth and developmental processes derived from the theory and paradigm are described. These theoretical linkages guide the assessment, implementation, and evaluation of the nursing care and provide the basis for describing the dynamic nurse-client relationship. PMID- 2228574 TI - Reorganization of community psychiatric services by professional nurses. AB - This article describes the reorganization of one part of an individual, home visiting service for mentally dysfunctional women into a group intervention. Deinstitutionalization has been followed by escalating health care costs, cost containment, and restructuring of services, affecting the already constrained resources for community psychiatric services. Faced with these challenges, a nursing staff, under the administration of a clinical specialist psychiatric nurse, began reorganization of a home visiting service with one trial group. The model group used the prior success reports of groups that were adapted prospectively with a focus on immediate needs and led by nurses for women. The aims were to enhance social supports of the clients while reducing their relapse rates and to reduce the personnel time and cost. Evaluation found that these objectives were met. Thus, the involvement of nurses in the assessment, planning, implementation, and evaluation of its services demonstrates success in the redesign and reorganization of community psychiatric services. PMID- 2228575 TI - A methodological approach to enhance external validity in simulation based research. AB - Simulation methodology, as exemplified by use of vignettes, has many advantages, such as standardization of data collection procedure, control of extraneous variables, and manipulation of variables of interest. The main shortcoming is its artificiality and therefore its limited external validity. To determine the degree to which findings from simulation research are transferable to the real world, a comparison can be made using the same measure on artificial and real situations, or the researcher can determine the degree to which a score on the simulation compares with a score in the field. The predictive validity approach was used in a study that used an artificial method to study patient assault. In this study, the intent was to determine the degree of accuracy that the subjects' causal attribution scores on an assault vignette were predictive of causal attribution scores in the actual assault situation. PMID- 2228576 TI - Cruzan and caring for others. PMID- 2228577 TI - An alternative to property rights in human tissue. AB - A three-tiered legal structure of the substances constitutive of human beings can accommodate property rights in new products created by the investment of labor in human tissue. PMID- 2228578 TI - Community values in Vermont health planning. PMID- 2228579 TI - Giving voice to the pragmatic majority in New Jersey. PMID- 2228580 TI - Public input into health care policy: controversy and contribution in California. PMID- 2228581 TI - A vision of the health decisions movement. PMID- 2228582 TI - Democracy and justice in health policy. PMID- 2228583 TI - Noncompliance in AIDS research. AB - Participants in AIDS research may justify non-compliance with protocols by a "coercion defense." While this defense may not be philosophically successful, a prudent social policy can enhance compliance by encouraging community participation and providing greater access to non-validated therapies. PMID- 2228584 TI - The Patient Self-Determination Act: yes. PMID- 2228585 TI - The Patient Self-Determination Act: not now. PMID- 2228586 TI - Ethics committees as corporate and public policy advocates. PMID- 2228587 TI - Business ethics in ethics committees? PMID- 2228588 TI - Nancy Cruzan in China. PMID- 2228589 TI - "Make me live": autonomy and terminal illness. PMID- 2228590 TI - Deciding for others. PMID- 2228591 TI - Ethics and objectivity. PMID- 2228592 TI - Cruzan: clear and convincing? How can they? PMID- 2228593 TI - Cruzan: On taking substituted judgment seriously. PMID- 2228594 TI - Cruzan: no rights violated. PMID- 2228595 TI - Cruzan:A hostage to technology. PMID- 2228596 TI - Serious migraine: a study of some epidemiological aspects. AB - Data are scant concerning some epidemiological aspects of those severe headaches which cause serious personal and economic morbidity. Our purpose was to study the incidence and other epidemiological features of patients suffering from severe migraine exacerbations, in an unselected population. The 64 patients who suffered from severe migraine bouts represented 10.5% of all the new walk-in neurological consultations in the area covered in this study. 70% of these patients were between 10 and 39 years old. Although females clearly predominated in all ages after fifteen, below this age there was a slight male predominance. The calculated incidence of serious migraine exacerbations was 90 per 100,000 people per year, the corrected incidence for females being 143/100,000 and for males 37/100,000. The highest incidence for females was in 15-19 year-olds (377/100,000) and for males in 10-14 year-olds (166/100,000). Our data seem to confirm the periodic nature of this condition since in 80% of patients the migraine bouts (ie: groups of attacks) lasted between two and nine months. Also they support the reported existence of genetic and hormonal factors in the susceptibility to migraine exacerbations. Our results may help in planning the public health aspect of migraine and add some light to the natural history of this common condition. PMID- 2228597 TI - Swimmer's migraine. AB - Three cases of sudden, severe headache occurring during swimming are described. A 51-year-old female had been engaging in a swimming exercise for about 20 minutes when she suddenly experienced a pulsating headache in the parietotemporal region, accompanied by nausea. A few days later, she experienced a similar episode, again during swimming practice. A 45-year-old male developed a pulsating headache with nausea immediately after diving into a swimming pool, and had a similar attack during diving practice 1 week later. A 32-year-old male developed a pulsating headache accompanied by nausea while swimming in the sea. In all three cases, blood pressure, pulse rate, neurological findings, cervical spinal x-rays, brain CT scans, and hematological findings were normal and the outcome was good. Although these patients' headaches were diagnosed as benign exertional headache, pathophysiologically they appeared to resemble the headache associated with sexual activity. PMID- 2228598 TI - Platelet monoamine oxidase activity in female migraine patients. AB - Platelet monoamine oxidase activity (MAO) in a group (n = 17) of white, female migraineurs during an acute migraine attack was similar to both the values obtained for the same group of patients two to three weeks after the headache episode (pain-free period) and to the results obtained for a group (n = 18) of sex and race-matched, age-comparable, drug-free healthy volunteers (blind study; substrate p-tyramine, 38.7 +/- 5.7, 41.9 +/- 8.8 and 43.0 +/- 3.4 or p methoxybenzylamine, 178.9 +/- 11.3, 177.2 +/- 6.9 and 181.0 +/- 9.7 nmole/hr/10(9) platelets +/- SD respectively). With each patient serving as its own control, MAO activity during the migraine episode and when pain-free failed to show a significant trend. Neither a number of other medical conditions nor the use of several medications appeared to significantly influence our results. The present work, while dealing only with a small but well defined patient population, argues against the possible usefulness of platelet MAO activity as a biological marker for migraine headaches. PMID- 2228599 TI - A protocol for butalbital, aspirin and caffeine (BAC) detoxification in headache patients. AB - The abuse of the combination drug containing butalbital 50 mg, aspirin 325 mg and caffeine 40 mg (or BAC), is commonly recognized by headache specialists as causing headaches. Despite this widespread problem, there is not a published treatment regimen for the BAC detoxification of patients. I describe such a protocol which was used four times in three patients. These patients fulfilled the diagnostic criteria of the IHS Headache Classification for headaches induced by chronic substance abuse (8.2) and analgesics abuse headache (8.2.2). These patients took between 150 and 420 BAC/month for 2-15 years. Two patients had previously undergone inpatient detoxification. One patient unsuccessfully tried detoxification twice as an outpatient. All patients were required to have psychological support prior to hospitalization for this protocol. BAC was discontinued. A pentobarbital challenge test corroborated butalbital dosage. The patients were given phenobarbital and caffeine which were tapered over several days. Dihydroergotamine (DHE) with metoclopramide was used (Raskin). Propranolol 60 mg bid was started. No narcotics were permitted. After hospital discharge, patients were allowed to continue subcutaneous DHE, as needed. One patient restarted BAC use after 8 months without it. The other two patients were still BAC free 18 and 14 months after detoxification. PMID- 2228600 TI - Thermographic findings in cranio-facial pain. AB - This work assesses the differences in the thermographic findings in the craniofacial and neck areas between normal individuals and patients with craniofacial pain or headache, and investigates the influence of muscle contraction on such findings. Thermographic records were taken in 10 healthy subjects and 47 patients suffering from craniofacial pain or headache of different kinds. In the patients with painful episodes the record was taken between attacks. In all the normal subjects and in 19 patients lateral thermograms were also taken during and after maximal tooth clenching for three minutes. The majority of the patients, as compared to the normal group, showed some thermal alterations and asymmetry. Such alterations seem to be due both to vascular instability and muscle contraction: these two factors may be variably superimposed in the different conditions. In patients with cluster headache or chronic paroxysmal hemicrania the presence on the symptomatic side of a cold spot along the supraorbital area and/or the inner orbital canthus, was a constant finding. We conclude that thermography is useful as an additional diagnostic means in patients with head and face pain, and that the clenching test may increase the amount of information provided. PMID- 2228601 TI - Dissociation between pain and autonomic disturbances in cluster headache. AB - The relationship between pain and autonomic disturbances in cluster headache was studied in 54 patients whose attack always recurred on the same side, and in 7 others whose attack had affected either side on different occasions. In one of these seven patients, facial flushing and ocular sympathetic deficit was observed on the original side of headaches. In most patients, the orbital region was warmer on the painful side but in three cases this region was cooler during and between attacks. Lacrimation and rhinorrhoea were more common in severe attacks, and the temperature difference between the orbits increased with increasing severity of pain. These findings support the view that certain autonomic disturbances in cluster headache are provoked by pain. Residual autonomic dysfunction could influence autonomic activity during cluster headache. If so, residual dysfunction on the pain-free side could explain the dissociation between autonomic disturbances and pain observed in a few cases. PMID- 2228602 TI - Sinus bradycardia, junctional rhythm and blood pressure increase during repeated cluster headache attacks. PMID- 2228603 TI - A study of the seasonal variation of migraine. AB - Available evidence supports the contention that migraine involves a disturbance in serotonin function. Several parameters of serotonin function in humans have been found to vary seasonally and may underlie the seasonal fluctuations observed in many clinical neuropsychiatric phenomena that are thought to involve serotonin dysfunction. We therefore postulated that migraine headaches might also vary seasonally and examined the admissions to our hospital over a 20-year period with a primary diagnosis of migraine. Peak admissions were found to occur most frequently in the spring for females in comparison to males (p less than or equal to 0.04, chi-square). The implications of these findings are discussed. PMID- 2228604 TI - Clinical characteristics of migraine and episodic tension-type headache in relation to old and new diagnostic criteria. AB - Eighty-one patients were diagnosed as having migraine, tension headache or both according to previously used criteria. Then we performed a standardized interview to determine the frequency and severity of headache characteristics used in the new operational diagnostic criteria of the International Headache Society (IHS). In every patient the original diagnosis fulfilled also the IHS criteria, but in 9 patients the criteria were only fulfilled in half or less of the attacks, and applying the IHS criteria they also achieved an additional diagnosis. In one patient these attacks did not fulfill the pain criteria and in 8 (4 migraine, 4 tension headache) they did not fulfill the criteria for accompanying symptoms. Overall the IHS criteria are sensitive and specific, but they may possibly be improved with regard to accompanying symptoms. The present study suggests that recording of frequency and graded severity of characteristics using a headache diary may further improve the distinction between the different types of headache. PMID- 2228605 TI - Radiation phobia as a culturally mediated reflex. PMID- 2228606 TI - Bomb survivor selection and consequences for estimates of population cancer risks. AB - Health records of the Japanese bomb survivor population [with the 1965 (T65D) and 1986 (DS86) dosimetry systems] have been analyzed and some evidence found for the selection effect hypothesized by Stewart and Kneale. This is found to be significant in only the first of the periods examined (1950-1958), and the effect diminishes in magnitude thereafter. There are indications that the effect might be an artifact of the T65D dosimetry, in which it is observed more strongly than in the DS86 data. There is no evidence to suggest that selection on this basis might confer correspondingly reduced susceptibility to radiation-induced cancer. If, however, one makes this assumption, as suggested by Stewart and Kneale, then current estimates of population cancer risks might need to be inflated by between 5% and 35% (for excess cancer deaths, Gy-1) or between 8% and 40% (for years of life lost, Gy-1) to account for this. It is likely that these figures, even assuming them not to be simply an artifact of the T65D dosimetry, overestimate the degree of adjustment required to the risk estimates. PMID- 2228607 TI - Predicted and observed early effects of combined alpha and beta lung irradiation. AB - The nonstochastic radiobiological effects of combined alpha and beta irradiation of the lungs of rats from inhaled radionuclides were studied. Both respiratory functional morbidity at 18 mo and mortality from radiation pneumonitis within 18 mo after exposure were examined for rats exposed to the beta-emitter 147Pm, the alpha-emitter 238Pu, or both combined. The results were used to validate hazard function models that were developed (1) for respiratory functional morbidity at 18 mo and (2) for lethality from radiation pneumonitis within 18 mo. Both models were found to adequately predict the experimental observations for chronic alpha plus beta irradiation of the lung. Based on this 18-mo study, a relative biological effectiveness of approximately seven was obtained for 238Pu alpha radiation compared to 147Pm beta radiation for both respiratory functional morbidity and lethality from radiation pneumonitis. However, the relative biological effectiveness for the alpha radiation is likely to increase with longer follow-up. PMID- 2228608 TI - Design issues in epidemiologic studies of indoor exposure to Rn and risk of lung cancer. AB - Recent data on indoor air quality have indicated that Rn (222Rn) and its decay products are frequently present in domestic environments. Since studies of Rn exposed miners have established that Rn decay products are a lung carcinogen, their presence in indoor air raises concerns about an increase in lung cancer risk for the general population. To directly evaluate lung cancer risk from domestic exposure to Rn and its decay products, as well as to evaluate risk assessments derived from studies of Rn-exposed underground miners, several epidemiologic studies of indoor Rn exposure have been initiated or are planned. This paper calculates sample sizes required for a hypothetical case-control study to address several important hypotheses and shows the impact of several difficult problems associated with estimating a subject's Rn exposure. We consider the effects of subject mobility, choice of the exposure response trend which is used to characterize an alternative hypothesis, and errors in the estimation of exposure. Imprecise estimation of Rn exposure arises from errors in the measurement device, exposure to Rn decay products from sources outside the home, inability to measure exposures over time in current as well as previous residences, and the unknown relationship between measured concentration and lung dose of alpha energy from the decay of Rn and its progeny. These methodological problems can result in large discrepancies between computed and actual study power. Failure to anticipate these problems in the design of a study can result in inaccurate estimates of power. We conclude that case-control studies of indoor Rn and lung cancer may require substantial numbers of subjects in order to address the many questions of importance that burden current risk assessments with uncertainty. We suggest pooling data from studies with the largest numbers of cases and with the most precise estimates of Rn exposure as the best approach for meeting present research needs. PMID- 2228609 TI - Energy deposition at the bone-tissue interface from nuclear fragments produced by high-energy nucleons. AB - The transport of nuclear fragmentation recoils produced by high-energy nucleons in the region of the bone-tissue interface is considered. Results for the differential flux and absorbed dose for recoils produced by 1-GeV protons are presented in a bidirectional transport model. The energy deposition in marrow cavities is seen to be enhanced by recoils produced in bone. Approximate analytic formulae for absorbed dose near the interface region are also presented for a simplified range-energy model. PMID- 2228610 TI - Evaluation of two thermoluminescent detection systems for medical imaging environments. AB - Thermoluminescent detectors (TLDs) can provide accurate and precise measurements for both patient and personnel dosimetry in the medical imaging environment. They have the advantages of tissue equivalency, an excellent dynamic range, and dose rate independence. In the work reported here, experiments with planar x-ray, fluoroscopy, and a 57Co source were conducted to test the repeatability and energy dependence of an LiF TL ribbon/automatic reader system and a four-element CaSO2 and Li2B4O7 badge/automatic reader system for diagnostic radiology and nuclear medicine dosimetry. The results indicate the usefulness and appropriateness of the TLD systems tested for both personnel and patient dosimetry in the medical diagnostic environment. PMID- 2228611 TI - Estimation of neutron dose equivalent at the mezzanine of the Advanced Light Source and the laboratory boundary using the ORNL program MORSE. AB - To investigate the radiation effect of neutrons near the Advanced Light Source (ALS) at Lawrence Berkeley Laboratory (LBL) with respect to the neutron dose equivalents in nearby occupied areas and at the site boundary, the neutron transport code MORSE, from Oak Ridge National Laboratory (ORNL), was used. These dose equivalents result from both skyshine neutrons transported by air scattering and direct neutrons penetrating the shielding. The ALS neutron sources are a 50 MeV linear accelerator and its transfer line, a 1.5-GeV booster, a beam extraction line, and a 1.9-GeV storage ring. The most conservative total occupational-dose-equivalent rate in the center of the ALS mezzanine, 39 m from the ALS center, was found to be 1.14 X 10(-3) Sv y-1 per 2000-h "occupational" year, and the total environmental-dose-equivalent rate at the ALS boundary, 125 m from the ALS center, was found to be 3.02 X 10(-4) Sv y-1 per 8760-h calendar year. More realistic dose-equivalent rates, using the nominal (expected) storage ring current, were calculated to be 1.0 X 10(-4) Sv y-1 and 2.65 X 10(-5) Sv y-1 occupational year and calendar year, respectively, which are much lower than the DOE reporting levels. PMID- 2228612 TI - Effectiveness of three natural biobarriers in reducing root intrusion by four semi-arid plant species. AB - Plant root depth, relative density, and an Intrusion Index were determined for three grass and one shrub species growing above three different natural biobarriers. High-clay content soil was the least effective barrier. Scoria (volcanic cinder) was most effective in excluding roots of crested wheatgrass and streambank wheatgrass. Root parameters for sagebrush and Great Basin wildrye were least growing over a biobarrier mixture of gravel and cobble. PMID- 2228613 TI - Atmospheric deposition, resuspension, and root uptake of Pu in corn and other grain-producing agroecosystems near a nuclear fuel facility. AB - Plutonium released to the environment may contribute to dose to humans through inhalation or ingestion of contaminated foodstuffs. Plutonium contamination of agricultural plants may result from interception and retention of atmospheric deposition, resuspension of Pu-bearing soil particles to plant surfaces, and root uptake. Plutonium on vegetation surfaces may be transferred to grain surfaces during mechanical harvesting. Data obtained from corn grown near the U.S. Department of Energy's H-Area nuclear fuel chemical separations facility on the Savannah River Site were used to estimate parameters of a simple model of Pu transport in agroecosystems. The parameter estimates for corn were compared to those previously obtained for wheat and soybeans. Despite some differences in parameter estimates among crops, the relative importances of atmospheric deposition, resuspension, and root uptake were similar among crops. For even small deposition rates, the relative importances of processes for Pu contamination of corn grain should be: transfer of atmospheric deposition from vegetation surfaces to grain surfaces during combining greater than resuspension of soil to grain surfaces greater than root uptake. Approximately 3.9 X 10(-5) of a year's atmospheric deposition is transferred to grain. Approximately 6.2 X 10( 9) of the Pu inventory in the soil is resuspended to corn grain, and a further 7.3 X 10(-10) of the soil Pu inventory is absorbed and translocated to grains. PMID- 2228614 TI - Short-term bioconcentration studies of Np in freshwater biota. AB - Short-term laboratory exposures were conducted to determine the potential accumulation of Np in aquatic organisms. Concentration factors were highest in green algae. Daphnia magna, a filter-feeding crustacean, accumulated Np at levels one order of magnitude greater than the amphipod Gammarus sp., an omnivorous substrate feeder. Accumulation of Np in juvenile rainbow trout (Oncorhynchus mykiss) was highest in carcass (generally greater than 78% of the total body burden) and lowest in fillets. Recommended concentration factors for Np, based on fresh weight, were 300 for green algae, 100 for filter-feeding invertebrates, for nonfilter-feeding invertebrates, 10 for whole fish, and one for fish flesh. PMID- 2228615 TI - Desorption kinetics and mobility of some radionuclides in sediments. AB - The desorption kinetics of five radionuclides, 85Sr, 137Cs, 60Co, 54Mn, and 65Zn, were studied for several coastal sediments, a few limnetic sediments, and one subsoil, using various aqueous solutions for extraction in batch systems. In a 2 wk desorption experiment, greater than 90% of most radionuclides sorbed were extracted by 6N-HCl, whereas in 1N-HCl approximately 30% of the 137Cs was retained within the sediments and a soil due to its fixation following intraparticle diffusion. For longer desorption periods (6 wk), reversible sorption with sediments could be seen for the 137Cs compared with the other four radionuclides in seawater. The EDTA-2Na solution extracted greater than 70% of 65Zn, 54Mn, and 60Co, and the ammonium oxalate extracted greater than 60% of 54Mn and 60Co. Readily exchangeable cations extracted by ammonium acetate were greater than 80% for 85Sr, approximately 50% for 137Cs, and 40% for 60Co and 54Mn. Many of the distribution coefficients for these radionuclides in coastal sediments obtained by desorption experiments were one order of magnitude or more larger than those obtained by the adsorption experiments. For 85Sr, larger-than-expected distribution coefficients were obtained in the desorption experiments, an indication of the irreversible formation of metal-oxyhydroxides during a slow reaction. Using batch and column diffusion experiments, it was recognized that 60Co and 54Mn are less strongly associated with coastal sediments under suboxic conditions, and their migration rates are greater in deeper layers of sediment than in the top layer, an indication that a single Kd model is inappropriate to forecast the behavior of radionuclides near sediment surface layers. PMID- 2228616 TI - Transmission of a Gaussian scanning beam through circular, square, and slit apertures: Part I. Theory. AB - Energy and power values for Gaussian profile scanning laser beams through circular, square, and slit apertures may be required for hazard analysis in laser safety programs. Equations describing the transmitted power for a Gaussian beam concentric and eccentric with circular, square, and slit apertures are given. Simple expressions of transmitted power and energy with a scanning laser beam across the square and slit apertures are derived. For the circular aperture, the transmitted power and energy can be calculated conveniently by using the correction factors from the graphic values or from the computer programs. PMID- 2228617 TI - Transmission of a Gaussian scanning beam through circular, square, and slit apertures: Part II. Experimental results for transmission through a circular aperture. AB - To perform an analysis of the hazards associated with scanned laser radiation to determine compliance with either federal or user standards, it is usually necessary to determine the amount of energy entering a specified aperture. A mathematical model has recently been developed that may simplify the hazard analysis. Experimental data and the mathematical model were compared for stationary and scanning Gaussian laser beams transmitted through a stationary 7 mm-diameter circular aperture, representing the dilated pupil of the human eye. Data were obtained for three values of laser beam diameter. The data and the mathematical model were found to agree within the estimated experimental error when the laser beam was concentric with the aperture, the situation typically encountered in compliance measurements. For two of the three laser beam diameters studied, as the eccentricity of the laser beam with respect to the center of the aperture was increased, the difference between the data and the mathematical model was found to increase. At the higher degrees of eccentricity, the percentage errors were shown to be highly sensitive to the errors in the determination of relative position. PMID- 2228618 TI - Retention and subsequent release of radioactivity from the incineration of wastes containing microspheres. PMID- 2228619 TI - Chemical risks from nuclear waste repositories: review of the literature. PMID- 2228620 TI - Radon in the human body from drinking water. PMID- 2228621 TI - Optimizing radiation worker protection: the practical application of risk analysis. AB - This paper presents the concepts of equivalent risk and risk minimization in optimizing radiation worker protection. When prescribing worker protection requirements and identifying work restrictions, all significant contributions to worker risk should be considered, not just the risk associated with radiation dose. This approach requires a practical application of risk analysis that allows comparison of a variety of risks. Examples of the types of worker risks that must be evaluated are given, and the author proposes that the scientific community develops a methodology for risk comparison that can be implemented via an expert system to facilitate risk analysis and decision making. PMID- 2228622 TI - Source inventory limits. AB - A new set of values has been developed for exempting sealed sources of radioactive materials from inventory. The criteria for exemption are: (a) the annual occupational dose from external radiation at 1 m from the source is approximately 100 microSv (10 mrem) or less; and (b) the source activity is approximately equal to the annual limit on intake by inhalation or less than 4 X 10(7) Bq (1000 microCi). These criteria were selected to correspond to an annual occupational dose of approximately 50 to 500 microSv (5 to 50 mrem) and a small potential annual risk of approximately 1 X 10(-6) to 1 X 10(-5) fatal cancers or less. PMID- 2228624 TI - EURADOS-CENDOS discusses ICRP draft recommendations. PMID- 2228623 TI - Sex discrimination in prenatal radiation exposure policies of U.S. NRC licensees: U.S. NRC staff position. PMID- 2228626 TI - Annual per caput effective dose equivalent of Beijing inhabitants from diagnostic x-ray procedures. PMID- 2228625 TI - Temperature and humidity effects of 222Rn adsorption on activated charcoal monitors. PMID- 2228627 TI - Certification and its discontents: a history of the moratorium. PMID- 2228628 TI - Health education credentialing--an idea whose time has come. PMID- 2228629 TI - A patient education program to improve adherence rates with antituberculosis drug regimens. AB - The design, logic, and results of a two-year health education study directed at improving rates of patient adherence to antituberculosis medical regimens are presented. An incentive scheme to reward positive health behaviors plus targeted educational counseling sessions was implemented in a randomized clinical controlled trial. The 205 subjects who participated in the study are categorized according to patients with active tuberculosis (n = 88) or preventive patients with no evidence of active disease (n = 117). Patients in each of these groups were randomly assigned to a special intervention (SI) group or a usual care (UC) control group and were followed monthly throughout their treatment program. While SI patients with active tuberculosis demonstrated higher levels of appointment keeping behavior and mean percent of medication taken compared to UC patients, no statistically significant differences between the two groups were found. Preventive therapy patients assigned to the SI group, however, were significantly more likely than UC patients to remain in care during their 12-month regimen (64% vs 47%; p = .003). Furthermore, SI patients had significantly higher levels of adherence to their medical regimen compared to UC patients (68% vs 38%; p less than .001). These results demonstrate the positive effects of a structured health education program on the improvement of continuity of care and adherence behavior among patients with tuberculosis. PMID- 2228630 TI - Identifying strategies for increasing employee physical activity levels: findings from the Stanford/Lockheed Exercise Survey. AB - While worksite exercise programs offer a number of potential advantages with respect to increasing physical activity levels in American adults, typical participation rates remain relatively low. The purpose of this study was to explore employee preferences and needs related to physical activity programming in a major work setting in northern California. Two-thirds (399) of a randomly selected sample of employees responded to a mailed survey. Male and female employees reporting no regular aerobic activity over the past two years more strongly endorsed a number of erroneous beliefs concerning exercise, reported less support for engaging in exercise both at home and at work, and avoided even routine types of activity to a greater extent than more active individuals (p values less than 0.001). Current exercisers reported use of a greater number and variety of motivational strategies as part of their exercise program than past exercisers who were not currently active (p less than 0.001). Respondents, regardless of exercise status and age, reported preferences for moderate intensity activity occurring away from the workplace which could be performed on one's own rather than in a group or class. Implications of the findings with respect to development of educational and behavioral programs for the current employee population are discussed. PMID- 2228632 TI - A validity problem in measuring exposure to mass media campaigns. AB - Recognition of radio and television messages included in three mass media campaigns designed to keep adolescents from starting to smoke cigarettes was measured in six treatment and four control cities (Standard Metropolitan Statistical Areas) in the southeastern United States. The telephone survey of 574 randomly selected adolescents found high recognition of campaign messages even in the areas where the campaigns had not been broadcast. Campaign messages that differed significantly from other anti-smoking messages were less likely to be falsely recognized. These results reinforce the need to include true control groups in mass media evaluations and to construct distinctive messages if exposure is an important aspect of campaign evaluation. PMID- 2228631 TI - Attitudes and behaviors of Hispanic smokers: implications for cessation interventions. AB - The smoking behavior of Hispanics, especially Mexican Americans, has been reported to differ from that of non-Hispanic whites, in both large gender differences in prevalence as well as a lower self-reported number of cigarettes smoked per day. This study compared the responses of a convenience sample of 263 Hispanic (44% Mexican American and 38% Central American) and 150 non-Hispanic white smokers, in order to identify other ethnic; gender, and acculturation differences in smoking behaviors. Hispanic women smoked fewer cigarettes and initiated smoking at a comparatively later age than Hispanic men; they were also less likely to smoke during pregnancy than non-Hispanic white women. Hispanics smoked more cigarettes on Saturday than other days, but this was not true for non Hispanic whites. Will power (voluntad propia) and knowing the negative effects of smoking were considered the most helpful techniques for quitting by Hispanics. Considering that light smokers are able to quit with less intensive cessation techniques, these data suggest that a properly developed health education community intervention may have an impact on smoking rates among Hispanics. PMID- 2228633 TI - Planning and implementing health promotion in the workplace: a case study of the Du Pont Company experience. AB - This case study describes the needs assessment, design, implementation, and preliminary evaluation of a comprehensive workplace health promotion program. The company had 110,000 U.S. employees at more than 100 locations engaged in a variety of manufacturing, research, sales, and support occupations in 1980. The PRECEDE framework was used to focus program planning and evaluation on key areas of health knowledge, attitudes, and behavior. The needs assessment included use of company morbidity and mortality data, a survey of medical and human resources staff, and a survey of employees, spouses, and pensioners. An in-house network of lay committees, site medical personnel, and corporate health education, nutrition and fitness specialists was used to staff critical program functions. Interventions included: public health approaches to program kick-off and health risk assessment; group and self-directed lifestyle change activities; recognition and awards; and workplace climate changes such as smoking policies that favor nonsmokers. One pilot location experienced a 47.5% decline in hourly employee absenteeism over six years versus a 12.5% decline in the total Du Pont hourly workforce. A number of lessons are discussed on how to improve the planning, implementation, institutionalization, and evaluation of health promotion programs in large industrial companies. Four areas where future research and practice should be focused include: reaching spouses, sales personnel, shiftworkers, and employees at small sites; balancing what is popular with what reduces risks over the long-term; documenting program impacts when research resources are scarce; and integrating health promotion programs with workplace medical, safety, employee assistance and benefits programs. PMID- 2228634 TI - Essential elements of self-help/minimal intervention strategies for smoking cessation. AB - Two decades of research suggest that self-help/minimal intervention strategies for smoking cessation may be the preferred means by which smokers stop and can produce success rates approximating those of more formal programs, at lower cost and with greater access to relevant populations. In order to make the best possible use of these self-help/minimal intervention approaches, the National Cancer Institute (NCI) supported a series of randomized, controlled intervention trials and, in June of 1988, convened an Expert Advisory Panel to address the question "What are the essential elements of self-help/minimal intervention strategies for smoking cessation?". The panel's recommendations were that: (1) Intervention efforts should focus on increasing smokers' motivations to make serious quit attempts; (2) Delivery of programs be broadened to include all smokers; (3) Programs be targeted to stages of cessation and specific populations; (4) All programs include (a) elements focused on health and social consequences of smoking, and (b) strategies and exercises aimed at quitting, maintenance of nonsmoking, relapse prevention, and recycling; (5) Materials and programs be made widely available rather than "fine tuning" existing programs or developing new ones; and (6) Programs make use of specific adjunctive strategies. In this way, a reacceleration of the decline in smoking prevalence may be realized in the 1990s and significantly contribute to the NCI's Year 2000 goals and the Surgeon General's aim of a smoke-free society. PMID- 2228635 TI - Virginia Bottomley: the caring face of the marketplace. Interview by Nick Robin. PMID- 2228637 TI - Public health: back to the future. PMID- 2228636 TI - Looking to a green tomorrow's world. PMID- 2228638 TI - Sense and science. PMID- 2228639 TI - Antenatal classes: becoming a mother. PMID- 2228640 TI - Maternal perceptions of child health care. PMID- 2228641 TI - Health visitors and health promotion. PMID- 2228642 TI - Community involvement: health mornings in the inner city. PMID- 2228643 TI - Infant feeding practices in Britain. PMID- 2228645 TI - Your rights at work. Contracts--beyond the bounds. PMID- 2228644 TI - Health promotion: running a health information desk. PMID- 2228646 TI - Race and benefits. 1. PMID- 2228647 TI - Pivotal role of early and sustained infarct vessel patency in patients with acute myocardial infarction. AB - Thrombolytic therapy in acute myocardial infarction unequivocally has improved short- and long-term mortality. The fundamental goal of therapy for evolving myocardial infarction is early and sustained infarct vessel recanalization. The mechanisms linking an open artery with improved long-term survival and other clinical outcomes are presented with use of data from extensive clinical trials. PMID- 2228648 TI - Clinical controversies surrounding thrombolytic therapy in acute myocardial infarction. AB - The treatment of acute myocardial infarction has changed tremendously in the past decade because thrombolytic therapy has become the treatment of choice for the patient with acute myocardial infarction. Although many issues have been resolved, several controversial issues remain unresolved. This article addresses thrombolytic agents in terms of their superiority in achieving infarct vessel patency and mortality reduction as well as the role of thrombolysis in patients who present with chest pain of greater than 6 hours' duration, who are elderly, and who have an inferior infarction. PMID- 2228649 TI - Role of angioplasty in myocardial infarction management strategies: a review. AB - The role of angioplasty in acute myocardial infarction has been extensively studied in the past few years. Although angioplasty in some circumstances can be the primary reperfusion intervention, logistic problems and the excellent results of intravenous thrombolytic therapy have resulted in postlytic angioplasty being the preferred use of this interventional strategy. Clinical trials of this strategy have not supported its routine use, however, and a much more selective application of postthrombolytic coronary artery dilation is advocated at this time. PMID- 2228650 TI - Effects of heparin versus saline solution on intermittent infusion device irrigation. AB - The purpose of this study was to compare the effectiveness of 1 ml of 0.9% sodium chloride with 10 units of heparin in 1 ml sodium chloride solution, both containing benzyl alcohol, in maintaining patency and reducing the incidence of phlebitis in patients with intermittent infusion devices. The subjects (N = 32) were randomly assigned in a double-blind experimental design. Repeated-measures analysis of variance revealed no significant difference between the groups in phlebitis or patency variables. The results from this controlled study would suggest that 0.9% sodium chloride is as effective as 10 units of heparin in sodium chloride solution in maintaining intermittent infusion device patency and preventing phlebitis. PMID- 2228651 TI - Obtaining reliable plasma sodium and glucose determinations from pulmonary artery catheters. AB - In critically ill patients, blood specimens are frequently withdrawn from intravascular catheters without consideration of possible infusate contamination, of test accuracy, or of undue blood loss. The reliability of sodium (Na+) and glucose determinations withdrawn from the venous infusion port of a pulmonary artery catheter was studied in 30 patients after cardiac surgery. Catheter patency was maintained by a saline and heparin infusate. Venipuncture samples for Na+ and glucose served as controls. A sample containing the dwell volume of the catheter and the stopcock (1 ml) was withdrawn and discarded, followed by fifteen 1 ml samples being taken for analysis. It was concluded that Na+ values are stable after discard of the catheter dwell volume and an additional milliliter of blood. Minimal clinical differences were found in the glucose values after discard of the catheter dwell volume and two additional milliliters of blood. PMID- 2228652 TI - Evaluation of manometer use in manual ventilation of infants in neonatal intensive care units. AB - Variations exist in the techniques used to perform manual ventilation in neonates and in the proficiency levels of nurses in neonatal intensive care units (NICU) who perform the procedure. This study was undertaken to determine (1) whether significant differences exist in nurses' ability to control prescribed peak inspiratory pressure (PIP) accurately when mamometers are used, as compared with when they are not used, during manual ventilation in NICU infants; and (2) whether the number of years of work experience nurses have in the NICU is related to manometer use and success in controlling prescribed PIP. The sample included 60 professional nurses whose experience ranged from 1 to 26 years. A statistically significant difference was found in nurses' ability to control PIP successfully when manometers were used as compared with when they were not used (t = 12.04, p = 0.001). Nurses with more experience tended to rely less on manometers to guide their manual ventilation techniques, but were also less accurate in controlling the delivery of PIP without the devices. We provide recommendations for clinical practice based on these findings. PMID- 2228653 TI - Effects of supplemental oxygen administration in an infant with pulmonary artery hypertension. AB - In patients with pulmonary disease, pulmonary artery hypertension often occurs as a result of pulmonary artery vasoconstriction, primarily from hypoxia and alveolar hypotension. In this report we describe the hemodynamic effects of breathing supplemental oxygen in a child with bronchopulmonary dysplasia and pulmonary artery hypertension. These hemodynamic effects include an improvement in oxygenation, an increase in systemic vascular resistance, and a decrease in the pulmonary vascular resistance. As a direct result of these changes in vascular resistances, alterations of heart rate, cardiac index, stroke volume, aortic pressure, oxygen consumption, and pulmonary artery pressure have been shown to occur. Oxygen is widely used to treat many physiologic conditions. However, during the administration of supplemental oxygen, rarely do we recognize the hemodynamic changes associated with its use. These hemodynamic effects must be clearly understood and appreciated before oxygen administration in any clinical situation. PMID- 2228654 TI - Impact of cardiac transplantation on the spouse's life. AB - The purpose of this research was to explore the effect of waiting for heart transplantation and the effect of the transplantation on the life, relationship, and reported stress of the patient's spouse. A cross-sectional descriptive design was used. The impact of both the pretransplant (waiting) and posttransplant periods was measured by using the Perception of Heart Transplantation Questionnaire (PHTQ) and the Subjective Stress Scale (SSS). Thirty spouses of patients who had undergone cardiac transplantation completed the mailed questionnaires. Results indicated that spouses perceived the pretransplant period to have a greater overall influence on their lives and relationships (p less than 0.001) than did the posttransplant period. Their impression of the posttransplant period was significantly more positive than of the pretransplant period (p less than 0.001). However, no significant differences between pretransplant and posttransplant stress scores were found. These results demonstrate the great impact of the waiting period on the spouse's quality of life. Additional research is needed. PMID- 2228655 TI - Improving family functioning after cardiac surgery: a randomized trial. AB - As part of a randomized clinical trial of in-hospital and postdischarge nursing interventions designed to facilitate the individual patient's recovery and improve the family's functioning after cardiac surgery, we followed 67 patient spouse pairs for 6 months after surgery. Family health was appraised by using three pencil and paper measurements: the Family APGAR, the Locke-Wallace Marital Adjustment Scale, and the Family Inventory of Resources for Management. Mixed effects analysis of variance did not detect differences for the main effect of intervention group; however, the main effect of time was significant for both patients' and spouses' APGAR scores and for patients' Marital Adjustment Scale scores, suggesting a pattern of response during recovery from cardiac surgery. PMID- 2228656 TI - Critical care family needs: nurse-family member confederate pairs. AB - In this study we explored the relationship between critical care family members' perceived needs and the assessment of these needs by a confederate sample of intensive care unit (ICU) nurses. Family needs were measured by using Molter's revised Critical Care Family Needs Inventory. Data consisted of 92 confederate pairs of Critical Care Family Needs Inventory responses obtained from 92 family members of adult patients hospitalized in a variety of ICUs and 49 ICU nurses providing direct care for these patients. Paired t tests (two tailed) were calculated to detect significant differences between confederate pairs of family members' perceptions and ICU nurses' assessments of the importance of the needs studied. Family members' perceptions and ICU nurses' assessments of the most and least important critical care family needs were identified. Significant (p less than 0.001 to p less than 0.05) differences were detected between confederate pairs of family members' perceptions and ICU nurses' assessments of the importance of 15 (50%) of the critical care family needs studied. Therefore, it appears that these nurses were only moderately accurate in their assessments of critical care family needs. Implications for nursing practice, education, and research were identified and discussed. PMID- 2228657 TI - Effects of anxiety on family members of patients with cardiac disease learning cardiopulmonary resuscitation. AB - The effects of anxiety on learning cardiopulmonary resuscitation (CPR) by family members of patients with cardiac disease was examined. Family members of hospitalized patients (n = 17), family members of nonhospitalized patients (n = 12), and a control group (n = 21) all took one of nine Heart Saver programs in which CPR was taught and performance evaluated. Subjects took the State Anxiety Inventory three times: immediately before the program, immediately after the performance test, and 2 months after completion of the program. Family members of hospitalized patients had significantly higher before-program anxiety scores than the other groups. This difference was not present immediately after the program or 2 months later. Family members of hospitalized patients showed a significant decline in anxiety over the three testing times. These outcomes support the benefit of teaching CPR to this group. PMID- 2228658 TI - Effect of activity on supraventricular tachyarrhythmias after coronary artery bypass surgery. AB - The purpose of this study was to evaluate patient activities, professional staff activities, backrest position, and diurnal variations as factors that may contribute to the onset of supraventricular tachyarrhythmias (SVT) after coronary artery bypass surgery (CABG). The activities surrounding the recognition of first onset SVT, as well as preoperative and postoperative data and patient characteristics were examined in 249 patients having CABG. One hundred seventy three patients qualified for the study; 28% of these patients (n = 49) had SVT. No statistical difference was found between the subjects with SVT and those without SVT when sex, cross-clamp time, creatine kinase peak, hemoglobin and hematocrit levels, and number of bypasses were examined. Patients who had SVT were older than those who did not: 64.8 years for the SVT group versus 60.7 years for the non-SVT group (p less than 0.01). SVT was rare in the first 24 hours after surgery, whereas 60% of the cases occurred during the next 48 hours, without significant diurnal variation: mean time of onset was 11:50 AM. No particular activity of the patient or nurse influenced the onset of SVT during the postoperative period in this group. PMID- 2228659 TI - Trapped-lung syndrome after cardiac surgery: a potentially preventable complication of pleural injury. AB - A case of trapped-lung syndrome after coronary artery bypass grafting (CABG) is presented. A significant pleural injury occurred during the bypass operation resulting in intrapleural hemorrhage, pleural fibrosis, and trapped-lung syndrome. The physicians caring for the patient when she was first seen with the trapped-lung syndrome were unaware of the potential relationship between the two prior bypass surgeries to this pulmonary complication. Recognition of the potential for pleural injury to occur after cardiac operations is important and may allow for earlier diagnosis and institution of appropriate therapeutic interventions. Early recognition and treatment with pleural fluid drainage and reexpansion of the collapsed lung may help prevent this potentially serious pleuropulmonary complication from occurring. In addition, the presentation of this pleuropulmonary complication may be delayed after the cardiac surgery, making early diagnosis more problematic. PMID- 2228660 TI - Semiventricular tachycardia. PMID- 2228661 TI - Chronic encephalitis caused by leukoencephalopathy. AB - As mentioned previously, both MS and PML are demyelinating conditions of the CNS and pose diagnostic difficulties in their differentiation because of similarities in their clinical findings. However, certain features unique to each of these diseases are helpful in clinical diagnosis. MS, unlike PML, is a disease of unknown cause. Polygenetic influences in combination with exposure to an environmental agent and immune-mediated factors may be operative in the pathogenesis of MS. Age of onset peaks in the third to fourth decades with a predominance in women, as contrasted with PML, which peaks in the fifth to sixth decades in most non-AIDS-associated cases with a slight predominance in men. MS is more prevalent in areas farther from the equator: North America, Europe, Australia, and New Zealand. Common initial symptoms seen in MS include bilateral limb weakness (with the legs being affected twice as often as the arms), hyperreflexia, spasticity, optic neuritis, diplopia, incoordination, and paresthesias. (Paresthesias are typically found in the lower limbs in a symmetric pattern, but may follow no obvious anatomic distribution and often do not correspond to the distribution of sensory symptoms. Vibration and position sense are more frequently disturbed than pain and temperature.) Intellectual impairment and mental deterioration are uncommon early in MS, whereas they are a more frequent initial presentation in PML. In addition, the presence of speech impairment and monoparesis or hemiparesis with homonymous hemianopsia is more suggestive of PML. Brain stem involvement is infrequent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228662 TI - Required request: why it has not significantly improved the donor shortage. PMID- 2228663 TI - Ethical issues in critical care. Who should decide? PMID- 2228664 TI - Wolff-Parkinson-White syndrome. PMID- 2228665 TI - The standard of care for the nursing diagnosis of ineffective airway clearance. PMID- 2228666 TI - Ethics of the 'doctor-nurse' game. PMID- 2228667 TI - [Callus distraction by an internal bone transport system in unilateral fixation]. AB - The problem of the treatment of bone defects can be solved by distraction osteogenesis as developed by ILIZAROV. This study shows how the bone transport technique can be adapted to every common external fixator while using a new internal distraction system. In 20 dogs a bone defect of 6 cm was performed at the femur. The femur was stabilized with an unilateral frame. A proximal or distal corticostomized bone fragment (length 2.5 cm) was descended through the bone defect (1 mm day). In 15 dogs a new regeneration of bone was observed. The quality of the regenerated bone depends upon stability of the fixation. In 5 dogs with osteotomy and rapid dislocation of the transported fragment no bone bridging was found. PMID- 2228668 TI - [Interlocking intramedullary nailing. A solid aiming device for distal locking]. AB - An additional aiming-device to the original Hielekes intramedullar locking nail system is presented and described. It simplifies greatly the difficult performance of distal locking of a tibial nail. The principle is a firm connection between the intramedullar nail and the aiming-device as well as between the aiming-device and the tibia. PMID- 2228669 TI - [Pedicled muscle flap in secondarily exposed plate of the lower leg]. PMID- 2228670 TI - [Recurrent carpal tunnel syndrome--caused by an inadequate surgical technique?]. AB - The carpal tunnel syndrome (CTS) is a common disease, and the decompression of the median nerve is one of the most often performed procedures in surgery. Within our patients from the 1. 12. 1987 to the 1. 12. 1988 we found 16 cases of recurrent CTS. Intraoperatively in more than 60% of the cases we could detect some sort of subluxation or even luxation of the median nerve and severe scarring involving the median nerve and the regenerated transverse carpal ligament in all cases. Considering the anatomy of the transverse carpal ligament, to guide the median nerve and the flexor tendon within the carpal tunnel, as well as serving as origin for the thenar musculature, especially for the opposition, one concludes that the simple dissection of the carpal ligament should be avoided. For the past 4 years we therefore have been performing a widening Z-plasty and reconstruction of the transverse carpal ligament, for the primary CTS as well as for revisions. The favorable postoperative results seem to confirm our theory. We discuss our operative technique as well as the results in CTS revision cases. PMID- 2228671 TI - [Ultrasonic diagnosis of meniscus lesions]. AB - Controversy exists about the value of ultrasonography of meniscal tears. We therefore examined 101 knee joints of 99 patients in a prospective study. Prior to the arthroscopy the menisci were scanned from an independent team by using 7.5 and 10.0 MHz ultrasound waves. 81 meniscal tears were seen at arthroscopy; 36% of these tears could not be detected with the scanner (? false negative results) while 20% of intact menisci showed positive echogenic structures, which were analysed as meniscal tears. It seems that ultrasonography of the menisci is still of experimental use without any clinical importance. PMID- 2228672 TI - [Clinical aspects, diagnosis and therapy of genuine bile duct cysts]. AB - During an eight-year period eight patients with intra- or extrahepatic bile duct cysts were treated at our institution. One patient belonged to Type I, four to Type IV and three to Type V according to the classification by Alonso-Lej/Todani. The main symptom among the Type IV patients was jaundice, among the Type V patients abdominal pain. The correct diagnosis could be established by ERCP in seven of eight cases. Two type V patients with disease mainly confined to one lobe of the liver could be resected, one patient was treated endoscopically, the others underwent biliary drainage procedures. PMID- 2228673 TI - [Traumatology and emergency medicine: helicopter evacuation in the Basel area]. AB - 999 patients were treated and evacuated by medical helicopter in the region of Basel between 1986 and 1988. 687 were trauma patients (70.5%) and among them 53.9% were directly treated on the accident scene. Mortality during the stabilization prior to transport (2.6%) and during transport (0.3%) was low. The presence of a physician in the helicopter allows fast and intensive in-field care. All life-saving procedures like endotracheal tubes (36.3%), closed intercostal drainage (7.4% of trauma patients) and cardiovascular reanimation (1.9), even hemostasis, or fixation of fractures are performed. Early in-field intensive care by medical helicopter decreases lethality and mortality and must be recommended by severe trauma. PMID- 2228674 TI - [Technique of bile duct revision]. AB - In view of the progress of endoscopic treatment of common bile duct pathologies the management of retained common duct stones following simple cholecystectomy has become a minor problem. Nevertheless duct stones should be recognized and removed during the cholecystectomy procedure. High risk patients or extreme forms of acute inflammation are an exception. For this purpose a standardized technique of revision of the common bile duct is recommended. We describe such a technique of the exploration of the common bile duct by means of manual extraction, Fogarty catheter, irrigation, distension--irrigation and flexible choledochoscopy. PMID- 2228676 TI - [Use of photoplethysmography with calibration in vivo for assessing venous hemodynamics of the lower extremity and particularly ambulatory venous pressure and refilling time after exercise]. AB - Several invasive and non-invasive methods are used actually for the appreciation of the morphology and the function of the venous system of the lower extremity. Hemodynamic parameters like the ambulatory venous pressure and the venous refilling time can not be determined without invasive measurements. This report describes the results of a prospective comparison of the ambulatory venous pressure and the venous refilling time with the in vivo calibrated photoplethysmography and with invasive measurements. Postural changes of hydrostatic pressure permitted in vivo calibration of the photoplethysmograph. We recorded quantitative photoplethysmography (PPG) ambulatory venous pressure and venous refilling time in 20 normal subjects, 20 patients with superficial varicosis and in 20 patients with chronic venous insufficiency. Quantitative photoplethysmography correlated closely with invasive measurements of ambulatory venous pressure with respect to estimated drop in superficial venous pressure and recovery time. PPG estimates of intravenous pressure in normal patients (24 +/- 9 mm Hg), in patients with varicosis (42 +/- 7 mm Hg) and post-thrombosis patients (63 +/- 9 mm Hg) agreed with ambulatory venous pressure measurements 22 +/- 9 mm Hg, 40 +/- 6 mm Hg and 61 +/- 6 mm Hg, respectively. Non invasive, quantitative photoplethysmography may prove to be an accurate estimate of ambulatory venous pressure in patients with superficial varicosis and in patients with chronic venous insufficiency. PMID- 2228675 TI - [Extracorporeal piezoelectric gallstone lithotripsy: initial surgical experience with a new treatment. Technique and indications]. AB - The extracorporeal piezoelectric lithotripsy (EPL) is a new method for non operative therapy of symptomatic gallbladder and problematic bile duct stones. The rare intrahepatic calculi were similarly disintegrated. Best results were reached with EPL as adjuvant measure or combined with oral cheno- and ursodeoxycholic acid therapy. EPL compared to other lithotripsy techniques is performed without any analgesia. That means advantage and patient's benefit. PMID- 2228677 TI - [Drug-induced acute arterial occlusion]. AB - An acute ischemia has almost its origin in a mechanical obstruction of the vessel caused by embolus, thrombose or dissection. An ischemia caused by medicament, excepted the erronated intraarterial injection of vasoconstrictive medicament, is very seldom encountered in the clinic. We describe the case of a young woman who was referred to our clinic for investigation and treatment of an acute ischemia of both limbs. In her past medical history she was treated because of a liver insufficiency occurring after a spontaneous abortion and received methylergometrine (Methergin) for uterine stimulation. Because of this unusual manifestation in a young patient with a complicated past medical history we considered the possibility of a drug induced ischemia caused by ergotamine derivate. The rapid recovering after treatment with chlorpromazine and nifedipine confirmed the suspected diagnosis. A well defined therapy of this rare complication has not been described; vasodilatators, nitroglycerin, calcium antagonists and even streptokinase and balloon dilatation are proposed. PMID- 2228679 TI - [Does the surgeon have to master sonography? Results of a survey in Swiss clinics]. AB - The range of applications for sonography in medicine is widening rapidly. More and more specialists are doing their particular sonographic examinations themselves. In other countries ultrasound is already part of the postgraduate surgical training. A questionnaire was sent to 142 surgical clinics in Switzerland to assess the present situation of ultrasound in surgery and to find out if changes are desirable. 112 questionnaires were returned. In 107 hospitals ultrasound equipment was available. Only 31 clinics had a surgeon trained in sonography amongst their staff, although 71 would like to start sonography in their clinic. Courses in sonography were considered necessary 87 times and most important, 83 clinics (74%) agreed to the introduction of ultrasound into the postgraduate training of Swiss surgeons. PMID- 2228678 TI - Experimental porcine orthotopic liver transplantation: a training protocol for transplantation in humans. AB - The authors suggest that, prior to human liver transplantations, exhaustive training be undertaken on an animal model in order to acquire the expertise required for this delicate procedure. The pig has considerable anatomic similarities to man, as well as a comparable physiological and hemodynamic sensitivity, and has been used as a model by our experimental team to perfect our clinical liver transplantation technique. In particular, a surgical model representing the adult donor/child recipient situation has been developed. Anesthesia, extracorporeal bypass procedure and the full surgical protocol are described. This operative protocol was elaborated to mimic as closely as possible the clinical situation. Our model also allowed us to undertake several relevant physiological and pharmacological studies during the transplantation procedure. PMID- 2228680 TI - [Surgical treatment of cholelithiasis and its complications. Comparison of 2 treatment periods]. AB - We have realized a retrospective analysis of all cholecystectomies performed during two five-year periods (period I: 1970 to 1974, period II: 1984 to 1988) for stone disease. We were especially interested in the development concerning the type of intervention, the diagnostic procedures, the morbidity and mortality. Our analysis showed in the second period the substitution of the preoperative diagnostic procedure away from the cholangiography up to the ultrasound, a significant decrease of interventions, a marked decrease of surgically performed papillotomies and a reduction of mortality. PMID- 2228681 TI - [Rupture of a subcapsular liver hematoma in the postpartum period associated with HELLP syndrome]. AB - We describe the case of a 31-year-old woman who underwent a section caesarean and 24 hours later a laparotomy for treatment of a ruptured subcapsular liver hematoma due to a HELLP syndrome. The HELLP syndrome (hemolysis, elevated liver enzymes, low platelets count) is a serious complication of the pregnancy with or without eclampsia. This complication has a high mortality and morbidity and can occur during the pregnancy or after delivery. The diagnosis of a subcapsular hematoma of the liver should be considered in patients with acute abdominal pain in the last trimenon or just after delivery. Laparotomy must be performed at the first signs of hemodynamic instability. PMID- 2228682 TI - [Acute appendicitis: avoiding unnecessary laparotomy in young women]. AB - Eighty-eight consecutive patients undergoing surgery for clinical diagnosis of appendicitis are reviewed. The diagnosis was correct in 71 (85%), incorrect in 17 (15%). Of these 17 patients 5 suffered from other diseases demanding surgical treatment (diverticulitis, cholecystitis, torsion of ovarian cyst, pyosalpinx). Pain migration, local tenderness and WBC greater than 10,000/mm3 were significantly associated with appendicitis, whereas duration of pain, defense musculaire and body temperature did not allow any discrimination. In men, the diagnosis was correct in 42 out of 43, whereas in women only in 34 out of 45. All 11 women with incorrect diagnosis were less than 35 years old. We conclude that the diagnosis of appendicitis is particularly difficult in women younger than 35 years. PMID- 2228683 TI - [Emergency diagnosis of cecal volvulus]. AB - Twelve cases of coecal volvulus have been analysed. Given typical signs, plain radiography of the abdomen should assure diagnosis. Chronic volvulus requires a colon contrast enema for confirmation of diagnosis.. Immediate laparotomy is mandatory. PMID- 2228684 TI - [Clinical aspects and therapy of intestinal non-rotation in adults]. AB - The intestinal non-rotation is a rare fetal disorder of the gut torsion. Its manifestation is very rarely seen in the adult, either in form of a volvulus of the midgut or ileocecal with an acute onset, or as chronic recurrent abdominal pain. Each diagnostic or therapeutic delay increases the risk of strangulation and may end as an abdominal disaster. We describe three own cases and we try to elucidate the diagnostic and therapeutic problems. Our proceeding: In the acute symptomatic form the explorative laparotomy with a consequent staging of the abdominal situs is the safest way to get an exact diagnosis. Therapeutically the procedure described by LADD is the best torsion prophylaxis; the ascending colon is sawn to the descending colon. Due to a paratopia, the appendectomy is recommended. In the chronic forms the contrast enema and the gastrointestinal barium study are the main diagnostic procedures. In the operation described by Fitzgerald and the ascending colon and the mesentery of the small bowel are- after incision of the common mesentery--fixed at their anatomical site. PMID- 2228685 TI - [Choice of technique in "difficult" inguinal hernias. Personal experience]. AB - The authors refer on their positive results in the treatment of so-called difficult inguinal hernias (relapsing or multiple hernias) with the use of prosthetic prolene mesh according to Stoppa's procedure (partly modified) through a preperitoneal approach after a Pfannenstiel's incision. On the other hand recurrent hernias in risky patients as well as gross hernias are treated by Rives' method which consists in a prolene mesh placement through the inguinal approach. PMID- 2228686 TI - [Surgical treatment of acute portal vein thrombosis]. AB - A concept of the surgical treatment of acute portal vein obstruction is presented: thrombectomy, small bowel resection and placing of a portal vein catheter for local application of heparin, allowing also angiographic control. Two cases are reported. With early diagnosis and surgical therapy acute portal vein obstruction seems to have a favorable prognosis. PMID- 2228687 TI - [Undifferentiated thyroid cancer: improved therapeutic results following initial radical intervention and early postoperative radiotherapy]. AB - During a 16-year period (1972-1988), 40 out of 477 thyroid cancer patients underwent thyroidectomy for undifferentiated thyroid carcinoma. To analyse the significance of "radical" versus "palliative" surgical procedures with regard to early postoperative course, operative complications and survival, all patients records were reviewed and actually followed up. A significant better survival was correlated with radical (n = 17) versus palliative tumor resection (n = 23) (p less than 0.001), and total thyroidectomy (n = 22) versus subtotal thyroidectomy (n = 18) (p less than 0.006). Radical surgery with early postoperative external irradiation revealed no postoperative mortality and only one symptomatic cervical tumor recurrence. In contrast, palliative surgery, particularly in the case of synchronous tracheotomy, was attended with a relatively high mortality (30%) and symptomatic local recurrences. The results of this study suggest that in undifferentiated thyroid carcinoma without infiltration of the esophageal or tracheal mucosa an attempt of radical tumor resection should be undertaken, since palliative surgical procedures revealed a significantly lower survival due to complications of persistent or recurrent cervical tumor infiltration and frequently were accompanied by local complications during the postoperative course. PMID- 2228688 TI - [Cystadenoma of the pancreas]. AB - We report on a patient with a microcystic adenoma of the head of the pancreas. Cystic neoplasms of the pancreas comprise only about 2% of all exocrine tumours. They can be divided into two distinct groups with different prognoses: the microcystic glycogen containing tumours, which are always benign and the mucinous cystic tumours, the majority of which shows malignant dysplasia. Clinically they manifest as a palpable abdominal mass with unspecific upper abdominal pain. Preoperative diagnosis is difficult to achieve. Computer-tomography and ultrasound are the main radiological facilities that allow some degree of differentiation. During operation a frozen section is mandatory to differentiate between a pseudocyst and a real cyst with epithelial wall. Resection of the tumour is the therapy of choice. The prognosis of the microcystic adenoma is good, the prognosis of the mucinous cystadenoma-cystadenocarcinoma is much better than the prognosis of the adenocarcinoma of the pancreas. PMID- 2228689 TI - [Desmoid tumor and Gardner syndrome: a little known surgical dilemma. Presentation of 2 cases]. AB - Two patients affected with Gardner's syndrome and desmoid tumour are presented: a 35-year-old man without polyposis coli who developed a clavicular posttraumatic desmoid tumour, and a 52-year-old woman with polyposis coli who died of an intra abdominal desmoid tumour 3 years after prophylactic colectomy. A close follow-up of patients with Gardner's syndrome for early detection of desmoid tumours after surgery is recommended. PMID- 2228690 TI - [IODIDA scanning for functional and morphologic assessment of the liver and bile ducts before and following surgical interventions in bile duct obstruction]. AB - PROBLEM: Full pre- and postoperative assessment is mandatory in the management of complex cases of incomplete biliary obstruction. Investigations should not only define the level of extrahepatic bile duct obstruction but also detect intrahepatic obstruction, give some index of liver function and of the dynamics of biliary flow. Computed tomography, ultrasonography and direct cholangiography are very valuable. IODIDA-scanning provides a non-invasive method which not only complements other studies but also gives information otherwise unobtainable. CLINICAL MATERIAL: In an initial retrospective study 36 patients, 12 of whom had previously undergone operation for biliary obstruction, were fully investigated with particular reference to the use of IODIDA-scanning. PROCEDURE: 2-5 mCi of 99mTc labelled IODIDA were injected intravenously and the liver and upper abdomen scanned at 1 minute intervals and displayed at 5 minute intervals during the first hour. RESULTS: All patients were studied on admission and then postoperatively at intervals. In 31 of 36 patients IODIDA-scanning gave reliable evidence of the level of obstruction of biliary flow and of the patency of biliodigestive anastomosis. Assessment of liver function before and after biliary reconstruction was also possible. CONCLUSION: IODIDA-scanning has proved a valuable non-invasive method for the assessment of liver parenchymal function, intrahepatic abnormalities and of bile flow in cases of complex biliary obstruction. This is particularly valuable with the Roux-Y biliary reconstruction since ERCP is impossible and PTC an invasive method which, although supplying an accurate picture of major biliary obstruction, fails to characterize hepatic function and bile flow. PMID- 2228691 TI - [Hemostasis in tumors of the pelvis by transarterial embolization]. PMID- 2228692 TI - [Bone and joint transplantation. Alternatives to bridging segmental bone defects and a model for allogenic bone transplantation]. AB - Fresh allogeneic diaphyseal bone segments were transplanted into 12 dogs. We attempted to improve the immunogenity and incorporation of the bone segments through "graft manipulation" with and without immunosuppression. Through clinical and radiological study during the 20-week experimental period, we observed transplant healing with differing structural phenomena. After autologous knee joint replantation in 4 dogs and allogeneic transplantation in 2 dogs (with and without revascularization and immunomodulation with Cyclosporin A) we present a canine model to investigate all open questions about the transplantation of allogeneic, fresh joints (i.e. transplant biology, immunology, and vitality). PMID- 2228693 TI - [Bile duct reconstruction in liver transplantation]. AB - Complications of the biliary anatomosis are common after liver transplantation. Even with improved techniques the frequency of biliary complications is approximately ten percent. Main reason for this high morbidity rate is the unfavourable blood supply to the biliary tract. A variant of reconstructions has been described and recommended. The end-to-end-choledochocholedochostomy over a T tube turned out to be the preferred technique in most centers. In cases of different diameter of donor and recipient biliary tract, the side-to-side choledochocholedochostomy provides a relayable alternative method. When the length of the bile duct doesn't allow direct anastomosis, the gallbladder-conduit may help to overcome this problem. The choledochojejunostomy with Roux-en-Y loop has become a frequently used biliary anastomosis, especially when the recipients bile duct is absent or otherwise destroyed. - Our own experience with fourteen liver transplantations shows biliary tract complications in three cases: a leakage and a stenosis of the anastomosis after choledochocholedochostomy were successfully transformed to a hepaticojejunostomy. In the third case, intrahepatic biliary stenosis were treated by percutaneous transhepatic dilatation. PMID- 2228694 TI - [The University of Wisconsin-solution and elective human liver transplantation]. PMID- 2228695 TI - [Organ donation for transplantation. Survey of opinions of physicians and paramedics in the province of Vaud]. AB - In 1987, two media campaigns were organized in Switzerland to promote donor cards. The purpose of this study was to test their impact on the medical community. Questionnaires were sent to qualified practitioners, doctors in training and intensive care nurses. It is concluded that the campaigns for organ donation must be repeated and that their quality can be improved. It is however more urgent to improve the level of knowledge among doctors and other health professionals. PMID- 2228696 TI - [Text, archiving, coding--integration with electronic data processing]. AB - For a successful computer-installation in the medical area you need a staff, which is used to work with computers in the daily routine. We tried with this project to establish the computer in a medical office by doing the whole patient related writings on a specially tailored software. Most of the daily routine can now be done with the help of the computer. A certain time-saving effect could be achieved, although this was not our first aim. On this base we are now able to solve other problems such as coding, statistics or archiving routines by using our established computer environment. PMID- 2228697 TI - [Electronic organization of patient records as a component of integrated medical informatics]. AB - Conventional patient records are not only inconvenient to store, their structure is often not consistent and faulty, research is difficult and quality control is not possible. One solution to this problem is the computerized patient record. It contains all necessary data beginning with the first medical statements and ending with the final results of treatment. At any time and from any with the system connected computer terminal it allows immediate access to all medical records. In addition to medical information also administrative data are stored. The here presented system of a computerized medical record has proven to be an effective tool in the daily work as well for clinical, administrative and research tasks. PMID- 2228698 TI - Beta-globin gene cluster haplotypes in Hb C heterozygotes. AB - Previous work has suggested that the beta C mutation arose on a relatively rare beta A chromosome with a unique haplotype, and these data have been used to postulate a single origin of the beta C allele. Most characteristic of this haplotype has been the absence of a Hpa I recognition site 3' to the beta-globin gene. We studied 40 patients with Hb SC, 11 with Hb AC, and one with Hb CC. Complete haplotyping was possible on 44 beta C alleles and 3' haplotyping was possible on an additional four beta C alleles. Our results support the predominence of a unique beta C haplotype which is characterized by the absence of the Hpa I site. However, one patient who was homozygous for Hb C had one beta C allele with an atypical haplotype which contained the Hpa I site. It is unclear at this time whether or not this represents a second origin of the beta C mutation. PMID- 2228700 TI - International Hemoglobin Information Center variants list. PMID- 2228699 TI - Hb Lepore-Baltimore in a north Sardinian family. PMID- 2228701 TI - International Hemoglobin Information Center. Alphabetical hemoglobin variant list. PMID- 2228702 TI - Entry of the hearing impaired into the health care system. AB - The current system of referral of patients complaining of hearing loss usually requires a dual appointment with otolaryngology and audiology. Most of these patients have sensorineural hearing loss for which there is rarely surgical or medical treatment. This study tests the hypothesis that these patients would receive appropriate treatment and that health care dollars would be saved if an audiological assessment could identify those patients who require medical or surgical care. One hundred consecutive patients whose sole complaint was hearing loss were evaluated using audiograms and "hearing abilities questionnaires" by five audiologists using subjective and objective criteria to determine the need for referral to otolaryngology. Audiologists determined the need for referral with an accuracy of 55% and 72% utilizing subjective and objective criteria, respectively. The questionnaire was found to be of little value. Audiologists may be able to function as the entry point into the health care system for patients complaining of hearing loss. We are encouraged by the results of this preliminary study, but improvement in the system by which audiologists detect disease is necessary. PMID- 2228703 TI - Management of chronic staphylococcal osteomyelitis of the temporal bone: the use of hyperbaric oxygen. AB - Hyperbaric oxygen (HBO) is an effective adjunct in the management of selected otolaryngologic problems including radiation-induced necrosis of the temporal bone, malignant external otitis, mandibular osteoradionecrosis and refractory osteomyelitis, soft tissue head and necrotizing fasciitis, compromised skin flaps and grafts, acute air or gas embolism, and otologic barotrauma. We describe the management of a patient with insidious Staphylococcus aureus osteomyelitis of the temporal bone by the use of HBO preoperatively and postoperatively in conjunction with surgical debridement. The possible application of angiogenic agents and tetracycline bone-labeling in combination with HBO therapy in the management of refractory neurotologic disease is discussed. PMID- 2228704 TI - Denker rhinotomy for inverted papilloma of the nose and paranasal sinuses. AB - Inverted papilloma of the nose and paranasal sinuses is an unusual benign neoplasm that has the propensity for local tissue destruction and an association with malignant degeneration. The tumor represents an inverted growth of epithelium rather than outward proliferation. It most commonly arises from the lateral nasal wall with growth into the nose and paranasal sinuses and only rarely originates from the septum. Presenting symptoms are usually unilateral nasal obstruction and clear rhinorrhea. Surgical excision is the recommended treatment though the aggressiveness of the approach has varied. Transnasal local excision has been associated with a high recurrence rate. Lateral rhinotomy with removal of the lateral nasal wall and wide local excision has a low recurrence rate and has been the recommended treatment by most authors since 1980. However, the poor cosmetic results in some patients due to the visible external scar is especially undesirable in young females. We present a series of 23 patients treated over a ten-year period. Fifteen underwent a Denker rhinotomy and medial maxillectomy through a sublabial approach without an external incision. The recurrence rate in our group is 27% with a mean 4.7 year follow-up. This recurrence rate lies between that reported for lateral rhinotomy and local transnasal excision. PMID- 2228705 TI - Hemangiomas of the nasal septum and paranasal sinuses. AB - Hemangiomas of the nasal septum and paranasal sinuses are rare; only 62 cases of septal hemangiomas and 32 cases of maxillary sinus/maxilla hemangiomas have been reported in the English literature. Hemangiomas should be considered in the differential diagnosis of any nasal mass lesion because biopsy may result in profuse bleeding and even death. We report the clinical presentation, differential diagnosis, etiology, and histologic appearance of paranasal sinus hemangiomas occurring in four of our patients. PMID- 2228706 TI - Cervicofacial actinomycosis in children. AB - Actinomycotic infections, once common in humans and cattle, are now rare causes of disease in man. This general group of organisms belongs taxonomically between the true bacteria and the fungi; however, the organisms behave clinically like true anaerobes. The organism, although phagocytized by the host cells, is not killed. Therefore, it is defined as a facultative intracellular parasite of the host. The protean manifestations of actinomycotic infections often mimic infectious processes, such as osteomyelitis or granulomatous disease, as well as neoplasia. It is therefore important for the surgeon to include actinomycosis in the differential diagnosis of cervicofacial masses in children as well as in adults. Being an anaerobe, the organism is difficult to culture and the diagnosis must be considered at the time of biopsy of a cervicofacial mass or when culturing a sinus tract. A case of a 12-year-old girl seen at Children's Hospital of Los Angeles prompted the review of our experience with this disease. In this child, actinomycosis presented as an expansile mass in the mandible. From 1956 to 1986, five children were treated for cervicofacial actinomycosis. Detailed case analysis, pathophysiology, clinical characteristics, and current treatment recommendations are presented. PMID- 2228707 TI - Abnormal coagulation profiles in tonsillectomy and adenoidectomy patients. AB - Preoperative coagulation profile screening is routinely performed in otolaryngology before tonsillectomy and adenoidectomy surgery in the United States. Recently there has been controversy as to whether this routine testing is necessary. To evaluate the need for this testing, we reviewed a series of patients with particular attention to abnormal coagulation profiles. Of 91 consecutive patients undergoing tonsillectomy, adenoidectomy, or both, four had abnormal preoperative coagulation profiles. Of these patients, one had von Willebrand disease, one had hypofibrinoginemia, and two had a transient acquired lupus-like anticoagulant. The latter condition, which causes a temporary prolongation of the activated partial thromboplastin time, is discussed in detail along with a review of the pertinent literature. We conclude that coagulopathies occur frequently enough to justify preoperative screening even in the absence of a positive history. PMID- 2228708 TI - Metastatic carcinoma of the jaws: report of a case. AB - Primary malignant tumors of the mouth and jaws usually do not present a diagnostic challenge to oral surgeons or otolaryngologists. However, recognition of metastatic tumors in the mouth and jaws is much more difficult. A case is presented of metastatic carcinoma from the lung to the soft tissue of the oral cavity. Histopathology of the lesions in the lung and oral cavity as well as the chest x-ray and the Panorex x-ray are presented. The patient refused palliative treatment, became malnourished, and died. A review of the pertinent literature is also presented. PMID- 2228709 TI - Infant hearing screening 1984 to 1989: the Henry Ford Hospital experience. AB - From 1984 to 1989 the Infant Hearing Screening (IHS) program at Henry Ford Hospital identified 1,300 infants as being "at risk" for hearing loss. The prevalence of significant sensorineural hearing loss in this sample was 1.4%. Additionally, 80 infants who passed the IHS program and reached 3 years of age were found to have normal hearing sensitivity by conventional audiometric techniques (ie, no false-negative predictions). There were three false-positive predictions. It was discovered that infants of low birthweight (ie, less than 1,500 g) were three times more likely to fail IHS than those whose weight exceeded 1,500 g. A higher return rate was found for infants failing an initial hearing screening conducted in the neonatal intensive care unit in comparison to those screened as outpatients one week postdischarge. The sensitivity and specificity of behavioral observation audiometry were 43% and 92%, respectively, when brainstem auditory-evoked potentials was used as the criterion validity measure. PMID- 2228710 TI - Management of voice disorders. AB - Voice disorders are commonly seen in general medical practice. In some cases voice disorders represent the presenting symptom for serious underlying disease. It is important for clinicians from internal medicine, pediatrics, and family practice to be able to identify those factors in the history or observed vocal symptoms which suggest need for referral for comprehensive voice evaluation as well as to understand the distinct but complementary roles of the specific disciplines (otolaryngology and speech-language pathology) involved in diagnosis and treatment of patients with voice disorders. PMID- 2228711 TI - Functional endoscopic sinus surgery: morbidity and early results. AB - Functional endoscopic sinus surgery is a new alternative to conventional sinus surgery as a means of managing recalcitrant sinus disease. This approach to sinus pathology focuses on the importance of the functional ostiomeatal complex and anterior ethmoid sinuses in the pathogenesis of sinus disease. In an effort to assess the morbidity and initial results of this procedure, 85 cases were reviewed. A total of 82% of the patients had bilateral maxillary and ethmoid sinusitis, and 45% had pansinusitis, frequently associated with allergic rhinitis (56%) and nasal polyps (58%). A total of 82% of the patients were operated on as outpatients under local anesthesia. There were no major complications associated with the surgery and minor complications were rare. Disease control was achieved in 88% of patients with short-term follow-up. PMID- 2228712 TI - The Bouveret syndrome: an unusual cause of hematemesis. AB - Gallstones are usually silent. Less commonly, patients with cholelithiasis develop symptoms and/or complications; biliary fistula occurs in 3% to 5% of the cases. When a large stone is passed and occludes the duodenum, gastric outlet obstruction (the Bouveret syndrome) may result. In reported cases, the stones are usually larger than 2.5 cm. The usual presenting symptoms are those of bowel obstruction: abdominal pain, nausea, and vomiting. Less commonly, the patients experience melena and, rarely, hematemesis. We describe a patient who had the largest stone reported to cause hematemesis rather than bowel obstruction and to be diagnosed endoscopically. The 5 X 4 X 3 cm stone was extracted surgically. Endoscopic diagnosis and extraction of stones up to 3 cm in size has been reported, avoiding the need for surgery. PMID- 2228713 TI - Cocaine-induced hepatonephrotoxicity: a case report. AB - Hepatotoxicity due to cocaine has been well described in animal models. There are few reports on cocaine-induced hepatic injury in humans; however, its link to rhabdomyolysis and renal failure is better known. We report a case of reversible acute hepatonephrotoxicity associated with recreational cocaine use. The proposed mechanisms responsible for its hepatic and renal toxicity are reviewed. PMID- 2228714 TI - Computerized literature searching in the ambulatory setting using PaperChase. AB - PaperChase, a self-service computerized literature search (SSCLS) service, was compared to conventional resources for accessing recent medical information by assessing user attitudes, search costs, and number of searches performed. The study was designed as a randomized controlled trial using survey instruments before and after the intervention. Accounting of PaperChase searches was monitored electronically, and costs of librarian searches were provided by the hospital library. Participants included 57 physicians in several specialties who were members of a group practice located in a suburban ambulatory care center. Responses were received from 67%. The experimental group received free, unlimited access to PaperChase over a one-year period, while the control group used conventional resources (manually self-performed searches and computerized MEDLINE searches performed free-of-charge by hospital librarians). The study disclosed no change in attitude of either those employing computers or SSCLS. Attitude scores in the experimental group showed statistically significant worsening in preference for SSCLS over textbook use and the estimation of SSCLS utility in the outpatient setting. The cost of PaperChase compared favorably to literature searches done by librarians. The self-reported numbers of literature searches of all types increased in the experimental group. PaperChase searches changed physicians' perceptions of patient treatment and outcome in some cases. While computerized literature searches may have a role in the outpatient setting, other resources remain important. Although only certain physicians are interested in using this method, this study shows that PaperChase can be a cost-effective alternative to MEDLINE searches performed by hospital librarians. PMID- 2228715 TI - Variability of quantitative sensory testing: implications for clinical practice. AB - The conventional estimation of motor, sensory, and mixed nerve conduction velocities reflects activity in the fastest conducting, heavily myelinated nerve fibers that are only a small proportion of the total. Unmyelinated and thinly myelinated fibers are not evaluated by this technique and numerically represent the largest group of fibers in human cutaneous nerves. The availability of new quantitative techniques to study this aspect of sensory function is an important addition to standard electrodiagnosis. Patient understanding and cooperation is essential because subjective responses are evaluated. We evaluated a reference range for 20 healthy subjects as well as variability on repeated testing. Vibration and thermal thresholds were measured bilaterally at several sites. Measurements were repeated at intervals ranging from two days to three months. There was no side difference but substantial site differences were noted for all measurements. Intraindividual variation was substantial but within the expected range for a psychophysiologic test. Close correlation was noted between various measurements at same and different sites, indicating a great degree of interindividual variation. The Marstock method is recommended for routine clinical use. PMID- 2228716 TI - Systemic dissemination of Pneumocystis carinii in a patient with acquired immunodeficiency syndrome. AB - Pneumocystis carinii is usually considered a respiratory tract pathogen; however, there are reported cases of limited and generalized dissemination of the organism from the lungs of immunocompromised patients. We present the autopsy findings of a 29-year-old male with acquired immunodeficiency syndrome (AIDS) and recurrent Pneumocystis carinii pneumonia who developed abnormal liver function tests. The patient had received aerosolized pentamidine because of toxic reactions to other modes of therapy. The postmortem examination revealed Pneumocystis in the lungs, liver, spleen, kidney, myocardium, thymus, pancreas, thyroid gland, bilateral parathyroid and adrenal glands, gastrointestinal mucosa, perihilar and mesenteric lymph nodes, and bone marrow. A high index of suspicion, especially in patients treated with aerosolized pentamidine, may lead to an increased recognition of disseminated pneumocystosis. Dissemination of the infection may be due to failure of the aerosolized drug to achieve adequate blood levels. As AIDS patients survive longer because of the developing therapeutic arsenal, disseminated pneumocystosis may be encountered with increasing frequency in these immunocompromised patients. PMID- 2228717 TI - Surgical removal of metastatic renal adenocarcinoma to the midbrain tectum: a case report. AB - A patient with adenocarcinoma of the kidney metastatic to the quadrigeminal plate of the midbrain presented with acute obstructive hydrocephalus and early tonsillar herniation. Because the majority of these carcinomas are resistant to radiation therapy, only limited treatment choices were available. Initially, a ventriculoperitoneal shunt relieved the hydrocephalus and neurologic symptoms. After a short course of improvement, with decompressed ventricles demonstrated by postoperative computed tomography, the patient developed additional neurologic signs, leading to the decision to excise the metastatic tumor. Convalescence was complicated but the patient survived for six months, succumbing to respiratory failure presumably caused by lung metastases. PMID- 2228718 TI - Management of advanced endodermal sinus tumor of the ovary with preservation of reproductive function. AB - Endodermal sinus tumor of the ovary occurs primarily in children and young adults. This tumor is classified as a germ cell tumor which comprises approximately 5% of all ovarian tumors. In the past, patients with this highly malignant tumor had low survival. However, with the evolution of effective adjunctive chemotherapeutic regimens, specifically vincristine, actinomycin D, and cyclophosphamide, survival rates have improved. In an attempt to continuously improve survival rates, other combination chemotherapeutic regimens are currently under investigation. Unlike epithelial ovarian malignancies, endodermal sinus tumor can be monitored by a specific tumor marker, alpha-fetoprotein (AFP). Serum levels of AFP can be followed from the preoperative period through the course of chemotherapy. When elevated, AFP has excellent predictability that persistent disease is present. Because this disease presents primarily in young females, preservation of reproductive function is of utmost importance. We report a case of advanced endodermal sinus tumor which was managed with conservative surgery only, followed by radical combination chemotherapy, resulting in preservation of normal reproductive function and total resolution of disease documented by second look laparotomy. PMID- 2228719 TI - Evaluation of the predictive power of progesterone receptor levels in primary breast cancer: a comparison with other criteria in 559 cases with a mean follow up of 74.8 months. The Breast Cancer Prognostic Study Associates. AB - A total of 559 women with primary breast cancer treated by modified radical mastectomy were followed for a mean of 74.8 months to evaluate the relationship of sex hormone receptor content in the tumor with time to first recurrence and to death due to breast cancer. The prognostic significance of progesterone receptor (PgR) status was evaluated in terms of estrogen receptor (ER) status, age (less than or equal to 49 years, greater than or equal to 50 years), extent of lymph node involvement, tumor size, and morphologic characteristics. Overall, patients with PgR positive (greater than 9 femtomoles/10 mg wet weight tissue) tumors experienced a significantly longer period to both first recurrence and death due to breast cancer, but this advantage was restricted to those whose cancer had metastasized to their axillary lymph nodes. For women with nodal involvement, the extent of this involvement and the size of the primary lesion had the greatest predictive value followed by nuclear grade and PgR status. In these node-positive patients, PgR positivity, although strongly associated with ER positivity, had a greater predictive value than that of the estrogen receptor per se. PMID- 2228720 TI - Single coronary artery. PMID- 2228721 TI - Practical value of echo Doppler evaluation of aortic and mitral stenosis: a comparative study with cardiac catheterization. AB - This retrospective analysis compares data derived by echocardiography and cardiac catheterization in the evaluation of aortic and mitral valve stenosis. Sixty seven patients, aged 69 +/- 12 years, underwent 76 catheterization procedures. In all studies the Doppler recording was technically adequate. In 64 studies of patients with aortic stenosis, correlation was good between the gradient obtained at catheterization (peak 51 +/- 28 mm Hg, mean 48 +/- 24 mm Hg) and the Doppler gradient (peak 73 +/- 29 mm Hg, mean 41 +/- 17 mm Hg) (R = 0.78 peak, 0.77 mean). In 15 studies the aortic valve area, 0.8 +/- 0.2 cm2, calculated by the simplified continuity equation, correlated well with the catheterization valve area, 0.7 +/- 0.3 cm2, calculated by the Gorlin equation (R = 0.80). In 14 studies in mitral stenosis patients, the mean gradient at catheterization was 11 +/- 5 mm Hg compared to the Doppler gradient of 8 +/- 4 mm Hg (R = 0.58). The mitral valve area was 1.1 +/- 0.3 cm2 by the Gorlin equation and 1.2 +/- 0.3 cm2 by echo Doppler, using pressure half-time. When cardiac rhythm, the presence and severity of regurgitation, and the cardiac index were analyzed, none was shown to have demonstrable influence on the accuracy of the Doppler study. Doppler echocardiography can be used reliably to assess valvular stenosis in a clinical, noninvasive laboratory where routine tests are performed and interpreted by more than one individual. PMID- 2228722 TI - Sensorineural hearing loss and the diagnosis of acoustic neuroma. AB - Sensorineural hearing loss and tinnitus are gradually receiving more attention in medicine due to advances in diagnosis and treatment. Acoustic neuromas can now be detected when they are small, and early microsurgical removal results in the lowest overall morbidity. We examine the historical development of acoustic neuroma management, discuss current diagnosis and treatment, and present illustrative cases from our recent experience. Complaints of tinnitus and hearing loss, especially when unilateral, require appropriate medical evaluation. PMID- 2228723 TI - A tribute to Henry Ford Hospital. PMID- 2228724 TI - Lymphocyte subpopulations in peripheral blood and the spleen from gastric cancer patients. AB - Lymphocyte subpopulations in peripheral blood and the spleen from gastric cancer patients were identified by either single or two color analysis with fluorescence activated cell sorter-IV (FACS-IV) using monoclonal antibodies. The absolute and percentages of CD3+ (mature T) cells and CD4+ (helper/inducer T) cells in peripheral blood from the advanced cancer patients were significantly lower than those from normal healthy controls. In peripheral blood, a significant decrease of CD4+ cells was due to the decrease of CD4+ CD45RA+ (suppressor inducer T) cells, while CD8+ CD11b+ (suppressor T) cells tended to increase with progress of the disease. CD4+ CD45RA+ cells located more predominantly in peripheral blood and spleen than in the splenic vein, while CD8+ CD11b+ cells were more predominant in the splenic vein. PMID- 2228725 TI - Gastric carcinoma with lymphoid stroma: pathological and immunohistochemical analysis. AB - Nineteen gastric carcinomas with lymphoid stroma were selected from 554 surgical cases and examined pathologically and immunohistochemically using formaldehyde fixed, paraffin embedded materials. Most showed ulcerative lesion and 15 cases located in fundic and cardiac gland regions. They were subdivided histologically into three groups, early (group I), localized (group II) and infiltrative tumors (group III), the number of cases being 2, 10 and 7, respectively. Lymph node metastases occurred in 3 cases in group II and 6 in group III, the latter showing a significantly higher incidence. The number of carcinoembryonic antigen and CA19 9 immunoreactive tumor cells was apparently smaller in gastric carcinomas with lymphoid stroma than in ordinary gastric carcinomas. Frequent presence of alpha 1 antichymotrypsin immunoreactivity characterized the tumor cells of gastric carcinoma with lymphoid cells. Stroma cells consisted of lymphocytes, plasma cells, granulocytes and histiocytes. Of these, the greatest number examined immunohistochemically was B cells and IgG cells, followed in descending order by T cells, IgA cells and IgM cells in the order given. A variable number of lysozyme immunoreactive histiocytes were also detected in all the cases. Gastric carcinoma with lymphoid stroma might be subclassified as a separate entity, although short term follow-up study did not demonstrate a favorable prognosis for this type of gastric cancer. PMID- 2228726 TI - A clinical and cytogenetic study of institutionalized mental retardates. AB - One hundred and four out of 110 patients in a residential institution for mental retardates were examined clinically and cytogenetically. Both conventional and folate deficient media were employed in order to detect both conventional chromosomal abnormalities and rare fragile sites. Conventional abnormalities were detected in 18 cases (17%). Rare folate sensitive fragile site at 2q13 was detected in one female patient. The same chromosomal aberration was also detected in the patient's mother who had a normal phenotype. Spontaneous expression of the rare fragile site at 2q13 was also observed. PMID- 2228727 TI - Microalbuminuria in subjects with no history of diabetes mellitus and hypertension: the relationship with hyperglycemia and high blood pressure at non diagnostic level. AB - 1969 subjects underwent albumin index [A.I., urine microalbumin (mg/liter)/creatinine (g/liter)] in early morning urine, 75 g oral glucose tolerance test (OGTT), determination of plasma lipids (total cholesterol, triglyceride and high density lipoprotein-cholesterol) and a resting electrocardiogram. There was no history of treatment for diabetes mellitus and hypertension. The relationship between microalbuminuria, and hyperglycemia or high blood pressure at non-diagnostic level was examined. Then, plasma lipid levels or changes in electrocardiogram were correlated with the degree of microalbuminuria. Subjects were divided into 4 groups according to 75 gOGTT and into 3 groups according to blood pressure based on WHO definition, and A.I. was divided into 4 categories (0-9.9, 10.0-19.9, 20.0-49.9, and 50.0-199.9 mg/gCr). Mildly or moderately enhanced microalbuminuria (A.I.) was found in subjects with hyperglycemia or high blood pressure at non-diagnostic level. In normotensive subjects, neither hyperglycemia in fasting nor after glucose challenge increased urine microalbumin above normal range, while in borderline hypertensives, diabetic glucose intolerance produced 2 and 3 fold increases respectively compared with normotensives. There was a linear increase in urine microalbumin in relation to the glucose intolerance in newly diagnosed hypertensives. No correlation could be found between microalbuminuria and plasma lipid levels, while the prevalence of electrocardiographic changes increased 3 folds in group with the heaviest microalbuminuria compared with the other 3 groups excreting less microalbumin. PMID- 2228728 TI - The circadian rhythm of intra-acinar profiles of alcohol dehydrogenase activity in rat liver: a microquantitative study. AB - Using microquantitative measurements of alcohol dehydrogenase activity in microdissected samples of liver tissue along the sinusoidal length, the intra acinar distribution profiles were studied in seven groups of female rats at different times during 24 h with a light phase from 6:30 h to 18:30 h. The mean values of alcohol dehydrogenase activity showed a circadian rhythm with a minimum at 13.30 h and a maximum at 17.30 h (p less than 0.001). However, the intra acinar gradients remained almost unchanged, indicating that increase and decrease in enzyme activity takes place simultaneously in all parts of the liver acinus. This observation, together with data from the literature, suggests that the circadian rhythm of alcohol dehydrogenase activity reflects variations in different liver cell constituents, rather than enzyme protein synthesis or proteolysis. PMID- 2228730 TI - An efficient histochemical method for deoxyribonucleic acids using a silver enhancement procedure. AB - An efficient histochemical method has been worked out for the demonstration of deoxyribonucleic acids (DNA) with light microscopy. This involves a hot hydrochloric acid-thiocarbohydrazide-silver proteinate sequence followed by a physical development procedure. When applied to tissue sections from rabbit organs such as the spleen, cerebellum and testis, the new method has given excellent discrimination of nuclear DNA in all cells examined. Thus, the method is higher in efficiency and visibility of reaction products than the traditional hot HCl-Schiff (Feulgen) method used hitherto. Its specificity is also high. PMID- 2228729 TI - Validation of bromodeoxyuridine immunohistochemistry for localization of S-phase cells in decalcified tissues. A comparative study with tritiated thymidine autoradiography. AB - Immunohistochemical detection of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd), which is incorporated by S-phase cells, offers a convenient way of studying the proliferation kinetics of cells in normal skeletal tissues and in bone containing/derived tumours. To assess the validity of using this approach on decalcified, paraffin embedded tissues, the BrdUrd method was compared with tritiated thymidine (3H-TdR) autoradiography, using rat tibiae labelled with both 3H-TdR and BrdUrd, fixed in Carnoy's fluid and decalcified in EDTA, prior to routine paraffin embedding. The distribution of BrdUrd-labelled cells correlated with the sites of cell proliferation in the growing rat tibia. Independent studies with each method on paired serial sections of double-labelled tissue, showed a highly significant correlation (r = 0.81, p less than 0.0003) in the numbers of labelled cells seen in autoradiographs and immunostained sections from the proximal tibial growth plate. Combined BrdUrd immunohistochemistry and 3H-TdR autoradiography showed that the majority of labelled cells in cartilage, bone marrow, and fibrous perichondrium and periosteum had incorporated both labels. These results show that BrdUrd immunohistochemistry is a valid technique for the study of dividing cells in mineralized tissues after decalcification. PMID- 2228731 TI - Biotinylated epidermal growth factor: a useful tool for the histochemical analysis of specific binding sites. AB - Epidermal growth factor (EGF) was labelled with biotin via modification of either the amino or carboxyl groups, using suitable reagents, namely biotinyl-N hydroxysuccinimide ester or biotinamidocaproyl hydrazide. To assure that the specific binding capacity of EGF is retained despite its chemical modification, displacement of the EGF by biotinylated derivatives in a routine binding assay was performed. The inhibitory potency compared to unmodified EGF was only slightly reduced. This result is the prerequisite for testing the usefulness of biotinylated EGF in histochemistry. The biotinylated probes were applied to sections of human tumour tissue and of monkey organs (liver, kidney, uterus of Cynomolgus and Rhesus monkey) to localize the specific binding sites for EGF. Formalin-fixed, paraffin-embedded tissue sections were deparaffinized and incubated with the probes at a concentration of 10 micrograms ml-1 at room temperature for 60 min. Specific binding of the EGF was visualized by the avidin biotin techniques (ABC). A positive reaction in conjunction with appropriate controls by competitive inhibition was seen for all monkey tissue sections and for the following number of cancer cases: breast carcinoma: 7/10; mesothelioma: 2/4; lung carcinoma: 1/3; colon carcinoma: 1/3. The staining properties were similar for both types of probes that differed in the functional group that is involved in modification by biotin attachment. However, the batches with modification of the amino groups stained more intensely and more distinctly than the carboxyl modified EGF. Overall, the data indicate that the ligand properties of the EGF are not impaired by biotinylation of the two types of functional groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228732 TI - Localization of adhesive proteins in two newly subdivided zones in electron lucent matrix of human platelet alpha-granules. AB - Platelet alpha-granules have been reported to consist of two zones, nucleoid and electron-lucent matrix, with different densities under electron microscopy. When washed human platelets were prepared by a rapid freeze-substitution method using liquid helium, we found that the electron-lucent matrix could be further subclassified into two zones having different densities: the intermediate and the light zones. The light zone was located at the periphery opposite the most dense nucleoid and contained several tubular structures with diameters of about 20 nm. The intermediate zone often laid between the nucleoid and light zone. By careful inspection, intermediate and light zones could even be identified in the platelets embedded in Lowicryl K4M, which where then used to localize several adhesive proteins in these two zone by immunocytochemical studies using the respective polyclonal antibodies. Fibrinogen, thrombospondin, and fibronectin were detected only in the intermediate zone. In contrast, von Willebrand factor (vWF) was localized only in the light zone, suggesting an association between vWF and the tubular structures in the light zone. In the nucleoid, none of these adhesive proteins were detected. Glycoprotein IIb/IIIa, a receptor for these adhesive proteins on the platelet surface, was detected not only on the outer surface of the cell membranes but also on the inner surface of the alpha-granule membrane. These data indicate that two zones with different densities in electron lucent matrix and functions exist in the platelet alpha-granules. PMID- 2228734 TI - Stage-dependent appearance of sulfhydryl oxidase during spermatogenesis in the testis of rat and hamster. An immunohistochemical study. AB - Sulfhydryl oxidase (SOx), an enzyme that catalyzes the oxidation of sulfhydryl compounds, appears in the spermatogenic cells of rat and hamster testes in a stage-dependent manner. It first appears in pachytene spermatocytes at stage I in both the animal species studied. SOx immunoreactivity is associated with mitochondria of these cells. The fate of such mitochondria is species-dependent. In rat, the immunoreactive mitochondria aggregate during maturation phase and are retained in the residual bodies. Spermatozoa free of SOx are released into the lumen. On the other hand, in hamster, the immunoreactive mitochondria arrange themselves around the midpiece of spermatozoa. In such a case, residual bodies lack SOx. The appearance of SOx coincides with the appearance of LDH-X in the spermatogenic cells. Like many other proteins such as LDH-X, RSA-1 and cytochrome ct, SOx provides yet another example of differential gene activation associated with a developmental process of gametes. PMID- 2228733 TI - Demonstration of distinct corticotropin releasing factor--containing neuron populations in the bed nucleus of the stria terminalis. A light and electron microscopic immunocytochemical study in the rat. AB - Immunocytochemical light and electron microscopic studies revealed two distinct populations of corticotropin releasing factor (CRF) - containing neurons, a dorsolateral and ventrolateral group, located in the bed nucleus of the stria terminalis (BST) of the rat brain. CRF neurons of the dorsolateral group had a smaller diameter and more primary dendrites than those of the ventrolateral group. CRF neurons in the dorsolateral BST had both somatic and dendritic spines, smooth contoured nuclei, and many dense and alveolate vesicles in their cytoplasm. Whereas, CRF neurons in the ventrolateral BST had only dendritic spines, irregularly-shaped indented nuclei and contained only alveolate vesicles in their cytoplasm. The only obvious difference in the type of unidentified afferents that synapsed on the CRF neurons of the BST could be attributed to the presence of the somatic spines on the CRF neurons of the dorsolateral population. Otherwise, the CRF neurons of the BST had a profuse innervation that included axosomatic, axospinous and axodendritic synapses. CRF-containing axons were distributed unevenly throughout the BST. The density of CRF axons was greatest in the lateral subdivisions of the BST, but the ventromedial BST contained many more CRF axons than the dorsomedial BST. The presence of these two CRF neuron populations in the BST suggests functional subdivision beyond previous proposals of a medial and lateral separation of function. Now there is additional morphological evidence to support the proposal of a dorsal and ventral separation of function within the BST. PMID- 2228735 TI - Bile duct ligation-induced redistribution of canalicular antigen in rat hepatocyte plasma membranes demonstrated by immunogold quantitation. AB - Extrahepatic obstructive cholestasis has been demonstrated to induce a redistribution of domain specific membrane proteins in rat hepatocytes reflecting loss or even reversal of cell polarity. In order to further characterize the redistribution of canalicular antigens, we used the Lowicryl K4M immunogold technique for examination of the effects of bile duct ligation (50 h) on the distribution of antigen in rat hepatocytes at the ultrastructural level and quantitated immuno-gold density in the three domains of the plasma membrane. In normal hepatocytes, antigen was localized almost exclusively in the canalicular domain while the sinusoidal and lateral membranes showed only weak immunoreactivity. Other localizations included organelles compatible with known pathways of biosynthesis and degradation. Bile duct ligation markedly reduced immunolabel in the canalicular and increased it slightly in the sinusoidal domain. The number and staining intensity of immunoreactive subcanalicular lysosomes and vesicles probably representing endosomes was augmented. Number of immunogold particles per micron of plasma membrane were 7.86 vs 2.46 (P less than 0.005) in the canalicular, 1.16 vs 1.38 (n.s.) in the sinusoidal, and 1.23 vs 1.08 (n.s.) in the lateral domain resulting in a canalicular decrease by 68.7% and a sinusoidal increase of 19.0%. Overall decrease in total plasma membranes was by 29.7% (P less than 0.05). Thus, our data show that the sinusoidal and lateral domains behave differently. Furthermore, quantitative immunocytochemistry demonstrates a decrease in the canalicular antigen density and suggests a sinusoidal increase. The present data agree with the concept that bile duct ligation results in a loss or even reversal of cell polarity in hepatocytes. PMID- 2228736 TI - Helix pomatia agglutinin binds specifically to the Golgi apparatus in cultured human fibroblasts and reveals two Golgi apparatus-specific glycoproteins. AB - Fluorochrome-coupled Helix pomatia agglutinin (HPA), but not other lectin conjugates with the same nominal specificity, bound specifically to the Golgi apparatus in cultured human fibroblasts, revealing a cytoplasmic juxtanuclear reticular structure. Unlike other Golgi-binding lectins the HPA-conjugates did not bind to the cell surface membrane or pericellular matrix. Experiments with 35S-methionine-labeled cells showed that HPA recognized two glycoproteins of Mr 170,000 and 400,000 among the secreted products of fibroblasts and two major cellular glycoproteins of Mr 40,000 and Mr 180,000 in Triton X-100 extracts of the cells. The two cellular HPA-binding polypeptides were also found in cells depleted of secretory products and in cells pulse-labeled shortly with 35S methionine and then chased with methionine containing medium up to 12 h. These findings suggest that the two cellular glycoproteins recognized by HPA are retained in the Golgi apparatus and are therefore not precursors of secretory proteins. The results suggest that there are two endogenous, Golgi apparatus specific glycoproteins in cultured human fibroblasts with terminal non-reducing O glycosidic N-acetyl galactosaminyl residues. PMID- 2228737 TI - The sheep pars tuberalis: an immunohistochemical study. Demonstration of the presence of glycoprotein and lipotropin hormones. AB - Using indirect immunofluorescence with fourteen different antisera raised against pituitary hormones and peptides, we characterized immunochemically the cells of the sheep pars tuberalis. The presence of LH- and FSH-containing cells, shown in previous studies, was also observed in the present investigation. In addition, we found TSH-containing cells, never observed in sheep, and beta LPH-containing cells. The latter hormone has never been found in any studied species. It appeared that a small amount of perikarya (less than 20%) were immunolabelled and, that the sheep pars tuberalis contained a majority of immunonegative cells as in the guinea-pig rabbit and rhesus monkey. This study may contribute to a better knowledge of the function of the sheep pars tuberalis. PMID- 2228738 TI - Glutamate producing aspartate aminotransferase in glutamatergic perforant path terminals of the rat hippocampus. Cytochemical and lesion studies. AB - The enzyme aspartate aminotransferase was demonstrated cytochemically in the rat hippocampus 4, 7, and 14 days after unilateral entorhinal cortex lesion. At the light microscopic level the enzyme showed a significant activity decrease in the ipsilateral entorhinal terminal field which was similar at all postlesion times investigated. Non-denervated areas, i.e. the inner one-third of the dentate gyrus molecular layer and the radiatum layer of CA2/3, showed an increase of aminotransferase activities. At the electron microscopic level in the entorhinal terminal field of the control (unoperated) side aspartate aminotransferase was localized preferentially in a great number of boutons, containing the cytoplasmic and mitochondrial isoenzymes. Following entorhinal lesion a significant loss of these positively reacting boutons was seen. Most of the degenerating boutons contained reaction product but a small number was negative for aspartate aminotransferase. From 4 to 14 postlesion days the positively reacting boutons of the non-denervated supragranular zone expanded outward into the denervated area according to the known terminal proliferation of the commissural and associational systems. The remaining denervated entorhinal terminal field was reinnervated predominantly by negatively reacting boutons (probably terminal proliferations of septal afferents) and by a small number of positively reacting boutons (probably terminal proliferations of the crossed temporo-dentate pathway). The presence of cytoplasmic aspartate aminotransferase in the terminals of a well-known glutamatergic system is discussed in relation to the possible importance of this enzyme for the production of releasable glutamate. PMID- 2228739 TI - Early replication signals in nuclei of Chinese hamster ovary cells. AB - DNA replication sites generally known as replicon domains were resolved as individual replication signals in interphase nuclei of permeabilized Chinese hamster ovary cells by immunofluorescent microscopy. Biotin-11-dUTP was utilized as a tool to label newly replicated DNA in permeable cells and to study the distribution of nascent DNA in pulselabel and in pulsechase experiments. Active sites of DNA replication were visualized in exponentially growing cells and in synchronized cultures throughout the S phase. Fluorescent images of replication sites were analyzed by standard fluorescence microscopy and in three dimensions by confocal laser scanning microscopy. The rapid increase in number of discrete foci of newly replicated DNA is an indication that DNA synthesis starts at limited number of sites in mammalian nuclei rather than at thousands of foci at the same time. PMID- 2228740 TI - [Occupation and cancer of the oral cavity, pharynx and larynx]. AB - There is increasing evidence of an association between occupational factors and head and neck cancer. The present paper reviews the most relevant epidemiological studies published within the last 30 years. Generally these studies indicate an increased cancer risk for "blue collar workers" exposed to dust or inhaled organic and inorganic agents. Moreover, the increased risk of head and neck cancer in most studies persists after adjustment for alcohol and tobacco consumption. More detailed, clinically orientated studies are necessary to provide a better understanding of the role of occupational factors in head and neck cancer. PMID- 2228741 TI - [History of surgical interventions in the paranasal sinuses]. AB - Hippocratices was the first to describe lesions that obstruct the nasal passages. Andreas Vesalius described the maxillary, frontal, and sphenoid sinuses. Mikulicz, Lothrop and Claoue are considered to have been the first to perform inferior meatal antrostomy of the maxillary sinus. Siebenmann was apparently the first to recommend suprameatal antrostomy in the middle meatus, which is now fashionable again. Grunwald, Hajek, Killian, Halle and Uffenorde developed endonasal ethmoid surgery to an established procedure. PMID- 2228742 TI - [Ultrasound-controlled fine needle biopsy of pathologic space occupying lesions in the head and neck area]. AB - We report 121 fine-needle aspiration biopsies of tumours and lymph nodes of the head and neck guided by ultrasound. The average minimal diameter of the lesions was 1.2 cm; the smallest lymph node was adjacent to the carotid artery and had a diameter of 0.4 cm. There were no complications. Of the cytological results 96% were confirmed by histology or by the subsequent clinical course. PMID- 2228744 TI - [Botulinum toxin treatment of synkinesia following facial paralysis]. AB - We report ten patients with unilateral synkinesias after facial palsy treated with botulinum toxin injections. All patients suffered from extensive mass movements around the eye. After periocular injections all patients showed much improvement: a period of 11 weeks free of symptoms was followed by a 9-week period of minimal symptoms. There were no important complications. The use of botulinum toxin injections is an effective therapy for mass movements after defect healing of facial palsy. PMID- 2228743 TI - [Squamous cell carcinoma in the area of the parotid gland. Metastasis or primary tumor?]. AB - A total of 61 patients with a histological diagnosis of squamous cell carcinoma of the parotid gland were studied. The patients were classified into three categories. There were 34 patients with a metastasis to the parotid gland from a squamous cell carcinoma elsewhere within the head and neck who presented on average 2.1 years (range 3 months to 7 years) after diagnosis of the primary tumour; in one case a salivary gland tumor presented 32 years after irradiation of a squamous cell carcinoma of the temple. Six patients had histological evidence of a metastasis within the parotid gland, but no evidence of a primary tumour. Twenty-one patients presented with a primary epidermoid carcinoma of the parotid gland. Two patients showed a primary squamous cell carcinoma of the parotid arising in myoepithelial sialadenitis. PMID- 2228745 TI - Subcortical gating in the human visual system during spatial selective attention. AB - The question of whether subcortical gating occurs as a function of spatial selective attention remains unsettled. This issue was investigated, using the paradigm of Eason et al. (1969) wherein subjects are instructed to attend to a specified location in a given visual field while attempting to ignore stimuli presented in the opposite field. Visual evoked responses falling within the 40-70 ms range were found to be significantly more negative when the location at which the evoking stimulus appeared was being attended to than when it was not. Also, later deflections (100-200 ms) were enhanced in amplitude and negatively biased. The very early effect provides further evidence for spatial attention-induced precortical gating. The later effects provide additional evidence for the amplitude enhancement of 'exogenous' components, along with the possible involvement of glial cell activity in the generation of slow wave negativity. PMID- 2228746 TI - Relations between slow (4 cps) EEG activity, sensorimotor speed, and psychopathology. AB - Slow rhythmic activity (SRA) in the frequency range from 2.5 to 5.0 cps was studied in 20 subjects (Ss) in order to examine its effect upon sensorimotor reactions and its possible relationship to psychological findings. With monopolar EEG derivations, maximal power density of SRA is found in frontal regions, whereas bipolar leads reveal maximum occurrence of SRA over posterior areas. Reaction times (RT) to visual and auditory stimuli increase significantly during the occurrence of SRA; the amount of this prolongation (ca. 74 ms) is independent of stimulus modality but significantly correlates with SRA frequency: the lower the frequency, the higher the RT increment. In psychological tests, most Ss with SRA displayed disturbances of emotionality as well as 'pathological' values in the subscales hysteria, hypochondria, psychasthenia, and paranoia, but none of our Ss was diagnosed as psychotic. There is a high correlation between the SRA frequency and the extent of psychological deviations: Ss with low SRA frequency values are more likely to reveal psychological disturbances than Ss with high SRA frequency. The possible origin and physiological impact of SRA is discussed and the desirability of further neurophysiological studies is emphasized. PMID- 2228747 TI - Effects of habituation and classical conditioning on reflex modification. AB - Reflex modification is the inhibition or facilitation of a reflex by a stimulus (S1) occurring prior to a reflex-eliciting stimulus (S2). Two experiments were conducted that investigated the effects of habituation of the orienting response (OR) and classical conditioning on reflex modification of skin conductance responses (SCRs). During the first phase of Expt. 1 two groups (Group S1 and the Control group) received pre-presentations of S1 (200 Hz). Another group (Group S3) received pre-presentations of a different tone (S3, 3000 Hz). During the second phase, Groups S1 and S3 received pairings of S1 with S2 (white noise), whereas the Control group received pairings of S2 with S1. The predictions were: if the OR to S1 produces reflex modification of the response to S2, then Group S1 and the Control group will display larger SCRs on the first trial of the second phase of the experiment compared to Group S3, in which the OR to S1 will produce reflex modification. However, if conditioned diminution of the unconditioned response (UR) elicited by S1 produces reflex modification of the response to S2, then there should be no initial differences between the groups in the second phase of the experiment. The results showed that SCRs in Group S1 were significantly larger in the second phase compared to Group S3. This result favors an OR explanation of reflex modification. In Expt. 2, the effect of conditioned diminution of the UR on reflex modification was further investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228748 TI - Early cognitive components of somatosensory event-related potentials. AB - Somatosensory event-related potentials (ERPs) were recorded during a selective attention task involving electrical stimuli delivered to index fingers or the left and right median nerves at the wrist. In 11 healthy, young subjects, ERPs were recorded from 6 scalp locations while they mentally counted the electrical stimuli designated as target. Sequential ERP events measured included N20 (negativity at 20 ms), P30, P45, N60, P100, N140, P180, and P400. Analysis of amplitude data indicated modifications of both early and late ERP events with selective attention. While electrical stimulation at the wrist yielded early ERP amplitudes that were larger overall and latencies that were generally shorter, the selection attention effects did not differ on the basis of site of stimulation. The early ERP selective attention effects had differing scalp topography, with the P30/P45 effect of maximal over postcentral gyrus and N60 effect maximal over prerolandic gyrus. The data further elucidate the temporal features and spatial distribution of somatosensory ERP processes involved in attentional activity. PMID- 2228749 TI - Biofeedback-produced hemispheric asymmetry of slow cortical potentials and its behavioural effects. AB - Two studies served to examine behavioural effects of slow cortical potentials (SPs). SPs were manipulated by means of a biofeedback procedure. The ability of human subjects to alter SPs differentially between the two hemispheres- specifically over the lateral aspects of the central sulcus--was tested by providing feedback of the SP difference between C3 and C4. In Expt. I, 21 of the 45 subjects produced hemispheric asymmetries of more than 2 microV between C3 and C4 on an average after 80 trials of analogue, continuous and immediate feedback. In Expt. II, SP changes were fed back digitally at the end of each trial. Within 120 trials, 20 of the 48 subjects reached the criterion of a minimum 2-microV difference in SPs between C3 and C4 on the average. Average differentiation remained significantly below the SP differentiations achieved for continuous feedback. Trials with feedback were followed by 'task' trials without feedback, during which subjects were still requested to produce SP changes but also had to complete a task: Either sensorimotor tasks (Expt. I) or forced choice handedness tasks (Expt. II) were presented to evaluate behavioural consequences of hemispheric SP differences. In subjects achieving the required SP differentiation it affected the behavioural output in agreement with the known functions of the respective cortical area. PMID- 2228750 TI - Occurrence of infraslow potential oscillations in relation to task, ability to concentrate and intelligence. AB - The occurrence of infraslow potential oscillations (ISPOs) of the brain was investigated during a listening and a resting condition in 44 subjects (Ss) with high (HAC) and low ability to concentrate (LAC). The occurrence of ISPOs was found in 36% of the Ss. While in the HAC group the occurrence of ISPOs did not change from listening to resting, in the LAC group Ss with ISPOs were affected by experimental conditions, showing ISPOs during the listening condition. For Ss with ISPOs only during listening a lower score was found for ability to concentrate, suggesting ISPOs as a possible underlying mechanism. For Ss with stable ISPOs a higher I.Q. was found compared to Ss without ISPOs. PMID- 2228751 TI - Ontogeny of the endorphinergic and dopaminergic modulation on the immobility reflex elicited by clamping in rats. AB - The effects of some dopaminergic and endorphinergic agonists and antagonists on the immobility reflex (IR) elicited by clamping the neck of the rat were investigated. We found that both morphine and haloperidol produce a significant increase in the duration of this IR at all ages tested (10, 20 and 300 days). The effect of apomorphine depends on the age of the rat, showing an increase in the duration of the immobility reflex only at the age of 10 days which was not counteracted by haloperidol. Naloxone alone showed a slight non-significant tendency to increase the duration of the IR but blocked morphine effects at all ages tested. When naloxone was added to apomorphine there was a peculiar effect: the duration of the immobility reflex was increased significantly in rats of 20 days and adults, but not in 10-day-old rats. The combination of morphine plus haloperidol showed the most marked potentiation of the immobility reflex at all ages tested. These results are discussed with respect to the development of dopaminergic and endorphinergic systems to control posture and movement during the IR, and its possible relation to the catatonia of schizophrenics. A hypothetical model explaining an interaction between the dopaminergic and endorphinergic systems in developing and adult rats is presented. PMID- 2228752 TI - Sensation-seeking: electrodermal and behavioral effects of stimulus content and intensity. AB - Although a number of studies support an arousal theory interpretation of differential sensation-seeking behavior, the conditions under which arousal correlates of this personality dimension are manifest is as yet unclear. Both theory and research suggest that among the external factors affecting the differential arousal response are stimulus relevance and stimulus intensity. The present study assessed the impact of these factors on both psychophysiological and behavioral responses. Subjects were preselected to represent the extremes of the sensation-seeking dimension, then exposed to auditory and visual presentations of a series of sexual and aggressive stimuli of systematically varied intensity. High sensation seekers gave larger amplitude SCRs to violent stimuli and larger initial responses to sexual stimuli presented visually, while verbal response intensities showed an opposite pattern. Overall, results provided support for an arousal theory interpretation of sensation-seeking, but suggested that the probability and magnitude of group differences is a somewhat complex function of stimulus intensity, stimulus modality, and perhaps other factors not yet assessed. PMID- 2228753 TI - Stability of resonance EEG reactions to flickering light in humans. AB - In order to study resonance phenomena in the EEG response to flickering light, 10 subjects were exposed to intermittent photic stimulation with the frequency of flashes linearly changing from 1 to 15 Hz and vice versa. Spectral analysis of occipital electrical activity revealed the occurrence of peaks of spectral density in those frequency components which coincide with the frequency of flashes. Such resonance peaks were observed at individually specific frequencies of stimulation. To assess the stability of the characteristics of the resonance phenomena, a repeated trial with 4-fold higher rate of changing the flash frequency was performed 3 months later. In a repeated trial the resonance phenomena were less pronounced, but were registered at the same frequencies as in the initial trial, showing significant test-retest reliability. The data obtained are interpreted in terms of provoking the activity of multiple brain oscillators having a narrow tuning to individually specific frequencies of photic stimulation by flickering light with the changing frequency of flashes. PMID- 2228754 TI - Initially high plasma prolactin levels are depressed by prolonged psychological stress in males. AB - Plasma levels of prolactin were determined by radioimmunoassay in medical students before and after an academic examination and corresponding control periods. Before the academic examination, both the males' and the females' prolactin values were higher than their control values; they were statistically significant, however, only in the males. After the examination, the prolactin values were lower than the control values in the males, but not in the females. The results partly explain the diverging opinions in the literature regarding the effect of psychological stress on plasma prolactin. PMID- 2228755 TI - Nasopharyngeally and vertex recorded P300's in normal subjects. AB - The P300 waveform has been associated with cognitive activity during information processing, and the hippocampus has been discussed as a possible generator of this waveform. This being the case some would argue that it should be possible to record the P300 with a shorter latency and greater amplitude from an electrode placed as near the hippocampus as possible. Under local anaesthesia we inserted a specially constructed needle electrode through the left nostril in the recessus pharyngeus close to the hippocampus. The results did not support the hippocampal hypothesis. Nasopharyngeally recorded P300's were found to have significantly decreased amplitudes and extended latencies when compared to vertex recordings. PMID- 2228756 TI - Aggression in dogs. PMID- 2228757 TI - Uveitis as a manifestation of Borrelia burgdorferi infection in dogs. PMID- 2228758 TI - "Steal phenomenon" proposed as the cause of blindness after arterial occlusion for treatment of guttural pouch mycosis in horses. PMID- 2228759 TI - Feedlot consultant shares insights on FDA investigations. PMID- 2228761 TI - Pricing a veterinary practice. PMID- 2228760 TI - Safe levels of antimicrobial residues in milk announced by FDA. PMID- 2228762 TI - Punitive damages. PMID- 2228763 TI - Power and sample size. PMID- 2228764 TI - Satisfying an itch to treat itching pets. PMID- 2228765 TI - ECG of the month. PMID- 2228766 TI - Repeated transplacental transmission of Neospora caninum in dogs. AB - Four litters of German Shorthaired Pointers from one owner developed a toxoplasmosis-like illness. According to the records, 29 of 39 dogs had hind limb paralysis. Six dogs from 2 litters were necropsied and had generalized encephalomyelitis. Tachyzoites and tissue cysts of Neospora caninum were found in the brain and spinal cord of each dog. Lesions were found in the eyes, extraocular muscles, or both in all of the dogs, and N caninum was detected microscopically in the eyes (retina and choroid in 1 dog), extraocular muscles, or both in 5 of the 6 dogs. Ocular lesions consisted of focal retinitis, choroiditis, mild nonspecific iridocyclitis, and myositis of extraocular muscles. Organisms stained with anti-N caninum serum, but not with anti-Toxoplasma gondii serum in an immunohistochemical test, except in 1 dog. In one dog, aged thick walled N caninum tissue cysts reacted mildly with anti-T gondii serum. PMID- 2228767 TI - Effects of sedation on intradermal skin testing in flea-allergic dogs. AB - Effects of 4 commonly used sedatives on the wheal-and-flare response to histamine and flea antigen were evaluated in 8 flea-allergic Beagles. Skin testing was performed in 12 separate occasions, 3 to 4 days apart. Twelve intradermal injections were given during each skin test: 5 doubling dilutions of histamine phosphate, 6 doubling dilutions of flea antigen, and a phosphate-buffered saline solution (negative control). Of the 12 intradermal skin tests, 8 were control tests performed on nonsedated dogs. The remaining 4 tests were performed on dogs sedated with xylazine, ketamine and valium combination, acepromazine, or oxymorphone. Oxymorphone had the most profound effect on skin test results, significantly (P less than 0.05) decreasing skin responsiveness in 8 of 11 test sites (by objective evaluation) and in 5 of 11 test sites (by subjective evaluation). Xylazine sedation enhanced skin test results in 4 of 11 test sites (by objective evaluation) and in 1 of 11 test sites (by subjective evaluation). In non instance did xylazine significantly decrease skin responsiveness to histamine or flea antigen. Xylazine is the recommended sedative in dogs when sedation is necessary for intradermal skin testing. PMID- 2228769 TI - Use of external coaptation for the treatment of avascular necrosis of the femoral head in a dog. AB - Avascular necrosis of the femoral head was diagnosed in a 5-month-old Schipperke, before the development of femoral head and neck collapse and resultant degenerative joint disease. External coaptation, consisting of an Ehmer sling, was used to prevent the bearing of weight during revascularization and reossification of the subchondral bone. Results of pelvic radiography (at 10 and 24 weeks) indicated that the early use of conservative treatment was successful in promoting resolution of the aseptic necrosis and in maintaining normal coxofemoral anatomic features and function. PMID- 2228768 TI - Comparison of two doses of aqueous bovine thyrotropin for thyroid function testing in dogs. AB - Thyroid function was evaluated in 20 healthy dogs by thyrotropin (TSH) response testing. Two dose regimens were used: 5 IU of TSH given IV and 1 IU of TSH given IV. Blood samples were collected prior to and at 4 and 6 hours after TSH administration. Serum was obtained and analyzed for total 3,5,3'-tri iodothyronine and thyroxine (T4) concentrations by radioimmunoassay. All dogs were classified as euthyroid on the basis of response to 5 IU of TSH at 4 and 6 hours. The 1-IU dose of TSH failed to induce adequate increase in T4 concentration in 7 dogs at 4 and 6 hours when the criteria for normal response were post-TSH serum concentration T4 greater than or equal to 3.0 micrograms/dl and serum T4 increase by greater than or equal to 100% over baseline serum T4 concentration. One IU of TSH induced increase in serum T4 concentration over baseline; however, the increase was significantly (P less than 0.05) less than that in response to a 5-IU dose at 6 hours after administration of TSH. PMID- 2228770 TI - Disseminated aspergillosis attributable to Aspergillus deflectus in a springer spaniel. AB - Disseminated aspergillosis attributable to Aspergillus deflectus was diagnosed in a Springer Spaniel with lethargy, lameness, anorexia, weight loss, pyrexia, lymphadenopathy, hematuria, and urinary incontinence. Necropsy revealed granulomatous inflammation and numerous fungal hyphae in many organs. The conidial heads of the fungus have a characteristic briar-pipe appearance in culture. PMID- 2228771 TI - Isolation of Microsporum vanbreuseghemii from skin lesions of a dog. AB - Routine examination of a 12-week-old Labrador Retriever revealed circular scaly lesions, with alopecia, on the lateral aspect of the left carpus and left upper eyelid. The geophilic fungus Microsporum vanbreuseghemii was isolated from the lesions. Topical treatment with chlorhexidine ointment resulted in resolution, with hair regrowth. PMID- 2228772 TI - Pigmented villonodular synovitis and plasmacytoid lymphoma in a dog. AB - A 4-year-old Labrador Retriever was examined because of progressive left hind limb lameness involving the stifle. A villous synovial mass was evacuated by synovectomy. Initially, the macroscopic and histopathologic features suggested a malignant fibrosarcomatous process; however, further histologic studies revealed lesions consistent with pigmented villonodular synovitis. Nine months later, the dog developed a large retroperitoneal tumor, with metastasis to the lungs and liver. The dog was then euthanatized. By histologic and electron microscopic examinations, the tumor was found to be a primitive plasmacytoid lymphoma. PMID- 2228773 TI - Congenital obstruction of the caudal vena cava in a dog. AB - A 16-week-old female Rottweiler was examined because of labored breathing and abdominal distention. Ascites, hepatomegaly, and pleural effusion were detected during physical and radiographic examinations. Selective angiography revealed a stenotic lesion at the junction of the caudal vena cava and the right atrium. A fibrous diaphragm with a pin-hole orifice was observed at surgery. Clinical signs of disease resolved after successful removal of the membranous obstruction. PMID- 2228774 TI - Giant cell tumor of the accessory carpal bone in a dog. AB - A 4-year-old Springer Spaniel was referred because of a 6-week history of progressive left forelimb lameness. A marked pain response was elicited by palpation over the left accessory carpal bone. Radiography revealed a lytic, markedly expansile lesion of the accessory carpal bone. The bone was excised, and pancarpal arthrodesis was performed. Histologic examination of the excised bone revealed giant cell tumor. At 14 months after surgery, the dog was using the limb normally. Radiography of the carpus revealed satisfactory progression of the arthrodesis, and thoracic radiographs were negative for metastases. PMID- 2228775 TI - Bronchial dysgenesis and lobar emphysema in an adult cat. AB - An adult male cat was examined because of chronic respiratory tract disease. Results of thoracic radiography indicated overinflation of the right lung, and atelectasis or agenesis of the left lung. Notable aerosol deposition (ventilation) to the right caudal lung lobe was seen by use of pulmonary ventilation scintigraphy. Postmortem findings suggested the primary pathoanatomic lesion was bronchial dysgenesis involving all but the right caudal lung lobe. PMID- 2228776 TI - Wound infection rates in dogs and cats after use of cotton muslin or disposable impermeable fabric as barrier material: 720 cases (1983-1989). AB - A retrospective study involving 720 dogs and cats that underwent a variety of elective surgical procedures was done to compare the effectiveness of reusable cotton barrier materials with that of a commercially available disposable barrier system for prevention of wound infection. The overall wound infection rate, using cotton barrier materials, was 3.1% and for disposable materials, was 4.4%. The difference between groups was not significant. PMID- 2228777 TI - Clinical and epizootiologic characteristics of dogs seropositive for Borrelia burgdorferi in Texas: 110 cases (1988). AB - Of 2,409 canine serum samples submitted to the Texas Veterinary Medical Diagnostic Laboratory between Jan 1, 1988 and Dec 31, 1988 and tested by immunofluorescent antibody technique for antibody to Borrelia borgdorferi, 132 (5.5%) had positive results. Clinical and epizootiologic characteristics of seropositive dogs from Texas (n = 110) were examined. Male dogs were more likely than female dogs to be seropositive for B burgdorferi. The most frequent clinical sign of disease described in seropositive dogs was lameness; neurologic, ophthalmologic, dermatologic, renal, and hepatic signs also were reported by referring veterinarians. PMID- 2228778 TI - Adverse drug reactions in cattle. PMID- 2228779 TI - What is your diagnosis? Agenesis of the left sixth rib. PMID- 2228780 TI - What is your diagnosis? Diffuse mineralization throughout the lungs and the stomach. PMID- 2228781 TI - Instruction on health care malpractice issues in entry-level physical therapy curricula. AB - In the face of an ongoing health care malpractice crisis, instruction on malpractice issues in entry-level health care professional education programs is vital for the legal well-being of prospective clinicians. A 1978 survey of US medical schools revealed that less than 40% required instruction in medical law. By 1989, 76% of US medical schools required medicolegal instruction. This article summarizes the results of a survey of entry-level physical therapy educational programs to determine whether a majority currently offer required malpractice instruction. The study found that the majority do offer such instruction. Half of the physical therapy programs with instruction in malpractice employ attorney instructors, essential for improving relations between health care and legal professionals. Graduate entry-level programs offer 11 or more hours of medicolegal instruction with greater frequency than undergraduate programs. Additional surveys of other allied health disciplines are recommended to ascertain other standards for entry-level malpractice-related instruction. PMID- 2228782 TI - An investigation of managed health care case managers. AB - Managed care case management is a relatively new concept within health and rehabilitation. As such, it lacks both definition and profiles of those providing services. This paper constructs a definition of managed care case management and presents the detailed results of a survey that identified the characteristics of case managers in the Midwest. The survey was mailed to 250 subjects. The respondents of the survey (N = 56) were relatively young (the largest number of respondents were 30 to 39 years of age), relatively new to their jobs (means = 2.2 years), and were typically employed full-time. They primarily served mental health (n = 43) and physically impaired (n = 30) clients. The highest number of their service referrals were made to vocational rehabilitation specialists, social workers, occupational therapists, nurses, and physical therapists. PMID- 2228783 TI - Profile of an allied health dean. AB - This study sought to gather baseline data about allied health deans in academic health centers in the US, their backgrounds, career patterns, role characteristics, and perceptions of professional development. The study also examined relationships that existed between a profile of allied health deans established in this study and other selected career variables. Allied health deans in 63 academic health centers were surveyed using a 55-item, self administered questionnaire, "Today's Allied Health Deans." The results revealed that the characteristics of allied health deans did not depart significantly from those of other academic deans. All deans had fairly uniform experiences in their roles as academic officers across the country. A review of their career patterns showed that they departed slightly from the traditional career ladder models established for other academic deans. PMID- 2228784 TI - Looking to the 21st century in schools of allied health. AB - During 1989, the members of the College of Health Deans participated in a Delphi study to identify objectives for schools of allied health professions now planning to meet the health care needs in the year 2000. There was consensus among the participating deans that 21 potential developments in health and health care are likely to occur by the year 2000 and that 16 objectives related to these developments are important for schools of allied health. PMID- 2228785 TI - The relationship between choice of college major and prevalence of adult children of alcoholics. AB - This study was designed to clarify the possible relationship between choice of college major and prevalence of parental alcoholism. A total of 190 occupational and physical therapy (OT/PT) students were surveyed using the Children of Alcoholics Screening Test. Results were compared to those from a group of 211 marketing, mixed, and undecided majors. The allied health OT/PT group reflected a 33% prevalence of parental alcoholism. Furthermore, a significant difference was found between the allied health and nonallied health groups. Awareness of this prevalence can help faculty identify students who are adult children of alcoholics and refer them for help before potential problems arise when they become helping professionals. PMID- 2228786 TI - A view from Washington. Allied health and the federal budget process. PMID- 2228787 TI - Where have all the graduates gone? PMID- 2228788 TI - Intermediate filaments in the inner ear of normal and experimentally damaged guinea pigs. AB - The hypothesis that proteins known to occur in glial cells in the central nervous system may be present in inner-ear supporting cells was investigated. Immunocytochemical techniques were used to look for the existence of two classes of intermediate filaments, vimentin and glial fibrillary acidic protein (GFAP), in cellular elements of the inner-ear epithelium in normal and experimentally damaged guinea-pig cochleas. Vimentin is present in two types of supporting cells in the normal organ of Corti: Deiters' cells and inner pillar cells. Differences in intensity and distribution of vimentin immunostaining are observed across the three rows of Deiters' cells. GFAP immunoreactivity was not detected in any supporting-cell type in the organ. Cochlear hair cells were not labeled for either GFAP or vimentin. Following hair-cell destruction by exposure to noise or the administration of aminoglycosides, GFAP and vimentin are not present in phalangeal scars replacing lost hair cells. PMID- 2228789 TI - Derivation of auditory filter shapes from notched-noise data. AB - A well established method for estimating the shape of the auditory filter is based on the measurement of the threshold of a sinusoidal signal in a notched noise masker, as a function of notch width. To measure the asymmetry of the filter, the notch has to be placed both symmetrically and asymmetrically about the signal frequency. In previous work several simplifying assumptions and approximations were made in deriving auditory filter shapes from the data. In this paper we describe modifications to the fitting procedure which allow more accurate derivations. These include: 1) taking into account changes in filter bandwidth with centre frequency when allowing for the effects of off-frequency listening; 2) correcting for the non-flat frequency response of the earphone; 3) correcting for the transmission characteristics of the outer and middle ear; 4) limiting the amount by which the centre frequency of the filter can shift in order to maximise the signal-to-masker ratio. In many cases, these modifications result in only small changes to the derived filter shape. However, at very high and very low centre frequencies and for hearing-impaired subjects the differences can be substantial. It is also shown that filter shapes derived from data where the notch is always placed symmetrically about the signal frequency can be seriously in error when the underlying filter is markedly asymmetric. New formulae are suggested describing the variation of the auditory filter with frequency and level. The implication of the results for the calculation of excitation patterns are discussed and a modified procedure is proposed. The appendix list FORTRAN computer programs for deriving auditory filter shapes from notched-noise data and for calculating excitation patterns. The first program can readily be modified so as to derive auditory filter shapes from data obtained with other types of maskers, such as rippled noise. PMID- 2228790 TI - S-100 immunoreactivity identifies a subset of hair cells in the utricle and saccule of a fish. AB - Certain hair cells of fish exhibit strong immunoreactivity to an S-100 antibody. By their spatial locations in the utricle and saccule, these hair cells appear to possess a relatively short kinocilium and a roughly ovoid cell shape. In the utricle, these cells are predominantly located in the striola. In the saccule, these cells are found within the central area of the epithelium. In both of these epithelia the strongly immunoreactive hair cells coincide with the locations of hair cells possessing F1 ciliary bundles. PMID- 2228791 TI - SEM analysis of the developing tectorial membrane in the chick cochlea. AB - The development of the tectorial membrane in the embryonic chick cochlea was studied using scanning electron microscopy. Chick embryos ranged in age from embryonic day 7 (E7) to post-hatching day 15. Our studies revealed that a fine filamentous matrix arose on the apical surface of the basilar papilla at approximately E7. This matrix was secreted by the supporting cells which encircled the hair cells. By E9, the early matrix had increased in volume but remained filamentous in structure, except at the inferior edge of the basilar papilla where it was condensed into a layer of laterally-oriented columns. At E9 the TM exhibited an additional layer of matrix, called the amorphous component. It appeared to originate from the homogene cell population, and attached to the early columnar matrix at the inferior edge of the basilar papilla. The two components of the TM were separated by a longitudinal ridge, called the 'track', which marked the inferior edge of the amorphous component. As the cochlea developed, the basilar papilla increased in width, the columnar component elongated and the track appeared to recede. These morphological findings point to separate developmental origins for the two components of the tectorial membrane. PMID- 2228792 TI - Psychophysical measures from electrical stimulation of the human cochlear nucleus. AB - Auditory performance on basic psychophysical tasks was measured in ten deaf patients with electrodes positioned near their cochlear nucleus. The device is called the auditory brainstem implant (ABI). Electrodes were placed during surgery to remove an acoustic neuroma, which results in the removal of the VIII nerve and, thus deafness. In patients who received auditory sensation from electrical stimulation we measured auditory performance on standard psychophysical tasks: thresholds, loudness growth, intensity discrimination, temporal integration, temporal modulation detection, gap detection, and forward masking. Plots of threshold as a function of frequency or biphasic pulse duration were markedly different from those of patients with cochlear implants. The difference in threshold functions is probably partly due to the biophysical difference in the neural elements stimulated. Another possibility is that part of the difference is due to the highly abnormal spatial pattern of activation in the cochlear nucleus from electrical stimulation, which prevents normal spatial integration of activity. The usable range of electrical amplitudes above threshold is comparable with that of cochlear implants, typically 10-15 dB. Little temporal integration occurs over a range of stimulus durations from 2-1000 ms. When compared at equivalent loudness levels, gap detection thresholds are similar to, or a bit longer than, gap thresholds in normal-hearing listeners and cochlear implant patients. Forward masking recovery functions are similar to those of normal listeners and cochlear implant patients. Patients' ability to detect amplitude modulation as a function of modulation frequency is similar to that of cochlear implant patients and normal listeners. Thus, direct electrical stimulation of the brainstem produces temporal resolution that does not significantly differ from that of normal listeners when compared in equivalent amplitude units. This implies that the limiting factors for these tasks are more centrally located, and not directly related to threshold mechanisms. Thus, a properly designed speech processor could preserve the important temporal features of speech for these patients. PMID- 2228794 TI - The effect of a low-frequency masker on loudness. AB - Intense low-frequency tones produce masking-period patterns in which the masking of a higher-frequency tone burst varies by up to 25 dB over the period of the masker. In this experiment, observers were asked to match the loudness of partially masked test-tone bursts in one ear by adjusting the level of unmasked bursts presented to the other ear. It was found that the variation in masked threshold over the period of the masker also affects loudness matches. This effect on loudness, although it decreases in size with increasing level above masked threshold, persists even 25 dB above masked threshold. PMID- 2228793 TI - Pentoxifylline increases cochlear blood flow while decreasing blood pressure in guinea pigs. AB - The effects of pentoxifylline on cochlear blood flow (CoBF) were investigated in anesthetized guinea pigs by laser Doppler flowmetry and intravital microscopy red blood cell velocity measurement. Intra-arterial infusion of pentoxifylline (3, 4, and 5 mg/kg/min) produced dose-dependent reductions in blood pressure, accompanied by significant elevations in CoBF that were not dose-dependent. These results are in general agreement with previous findings from our laboratory utilizing normotensive and spontaneously hypertensive rats, however, in contrast with rats, guinea pigs revealed an initial decrease in CoBF followed by an increase. Also, pentoxifylline produced relatively smaller elevations in CoBF in guinea pigs as compared with those previously reported in rats. Taken together these results support the hypothesis that pentoxifylline increases vascular perfusion by decreasing blood viscosity and increasing the plasticity of red blood cells. PMID- 2228795 TI - Evoked response narrow-band noise masking patterns in the chinchilla. AB - Narrow-band noise masking patterns were measured at 0.5, 1, 2 and 4 kHz in the chinchilla using the auditory evoked response from the inferior colliculus. At low masker levels, the masking profiles were symmetrical and centered on the masker. However, as masker level increased, the masking profiles spread predominantly toward the high frequencies. The masking profiles obtained at 0.5 and 1 kHz, exhibited a broad plateau extending 1-2 octaves above the masker at the highest masker level (70 dB SPL) whereas those obtained at 2 and 4 kHz showed a peak. In contrast to tone-on-tone masking profiles, none of the narrow-band noise masking profiles contained a low-threshold notch on the high frequency side of the masker. The evoked response masking profiles obtained in the chinchilla were slightly wider, but qualitatively similar to those measured psychophysically in humans. Thus, the evoked response narrow-band noise masking profiles may provide a convenient way of evaluating the spread of masking in difficult-to-test subjects. PMID- 2228796 TI - Acetylcholinesterase-positive innervation in cochleas from two strains of shaker 1 mice. AB - Shaker-1 is a recessive gene mutation on chromosome 7 in mice, causing both deafness and neurosensory degeneration in the inner ear. A failure of efferent innervation to the outer hair cells is being implicated in the cause of deafness (Green, 1981). To investigate the efferent innervation, we examined the cochleas of two strains of shaker-1 mutants: Sh1/Le (25 and 45 days old) and FS/Ei (28 and 68 days old), using enzymatic staining of acetylcholinesterase (AChE) for the light and electron microscopes, and also by measuring the activities of AChE and of AChE molecular forms. The enzyme levels in the SH1/Le and FS/Ei homozygotes (sh-1/sh-1) were within the range of those in SH1/Le heterozygotes (+/sh-1) and in normal mouse strains (C3H/HeJ, 129/SvJ, ICR). The picture of AChE-positive innervation in both strains differed. In the SH1/Le mutants at 25 days, the innervation appeared normal, but by 45 days it showed a marked atrophy. In the FS/Ei mutants, the degeneration was already evident by the 28th day. In the younger animals of both mutants, large differentiated vesiculated nerve endings were ultrastructurally detected in synaptic contact with outer hair cells. The preservation of AChE activity and of the expression of AChE molecular forms up to 68 days indicate that the shaker-1 cochlea may initially possess a normal input of AChE-positive efferent innervation. The late onset and the slow course of the degeneration of AChE-positive innervation seen in the SH1/Le mutants suggest that the loss of efferent endings may be, contrary to previous suggestions, the consequence rather than the cause of the shaker-1 pathology. PMID- 2228797 TI - Acetylcholine, carbachol, and GABA induce no detectable change in the length of isolated outer hair cells. AB - The mechanical and electrical properties of cochlear outer hair cells (OHCs) are suggested to modulate transduction by inner hair cells. These properties of OHCs are presumably regulated by efferent neurons which use several transmitters including acetylcholine (Ach) and gamma aminobutyric acid (GABA). Since it had been suggested that Ach causes isolated OHCs to shorten visibly, this study was designed to investigate whether GABA also alters the length of OHCs. OHCs were isolated from the guinea pig cochlea by mechanical dispersion after collagenase treatment. Cells were initially selected by strict morphological criteria. In addition they were only included in further studies if they attained a constant length during 10 min of superfusion with buffer solution. Neither GABA (20 microM: 100 microM), Ach (5 mM; 10 microM with 10 microM eserine) or carbachol (10 microM; 100 microM) altered OHC length when applied in iso-osmotic Hank's balanced salt solution (total number of cells tested, 72). If a change in length occurred it must have been smaller than 0.3 microns, our detection ability. In contrast, high potassium and variations in osmolarity changed hair cell length by 3-10% in agreement with other reports. PMID- 2228798 TI - Insulin stimulates protein synthesis and phospholipid signaling systems but does not regulate glucose uptake in the inner ear. AB - High-affinity insulin receptors exist in the organ of Corti (Kd = 1.1 +/- 0.5 nM) and in the lateral wall (stria vascularis and ligamentum spirale; Kd = 1.1 +/- 0.4 nM) of the inner ear of the guinea pig as determined by the binding of radiolabeled porcine or bovine insulin in vitro. Carrier-mediated transport of glucose (defined as the cytochalasin B-sensitive part of total uptake) was measured in vitro with 2-deoxy-D-glucose as the substrate. Its Km was 188 microM in the lateral wall (r = 0.99 and 0.94, respectively). Neither the Km nor the rates of transport (0.20 +/- 0.10 pmol/micrograms protein/hr in the organ of Corti, and 0.56 +/- 0.34 pmol/micrograms protein/hr in the lateral was) were affected by insulin. In contrast, 0.1 mM ouabain decreased deoxyglucose uptake in the organ or Corti by 37% and in the lateral wall tissues by 45% indicating the presence of an active, Na(+)-dependent transporter in these tissues. Insulin influenced both protein and lipid metabolism in the inner ear. Proteins and lipids were labeled in situ by perfusion of the perilymphatic space of the cochlea with [3]-leucine or [32P]-orthophosphate and [3H]-glycerol, respectively. Thirty nM insulin stimulated the incorporation of [3H]-leucine into protein of the organ of Corti from 39 to 56 pmol/mg protein but was ineffective in the tissues of the lateral wall. In the organ of Corti, [32P]-orthophosphate was incorporated into the phosphoinositides and phosphatidate, and 30 nM insulin increased this incorporation by 101 to 149%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228799 TI - Basic properties of auditory-nerve responses from a "simple' ear: the basilar papilla of the frog. AB - Spike discharges initiated by mammalian inner hair cells are produced by a complicated system involving both mechanical and neural components that normally operate in a bi-directional configuration involving multiple feedback loops. In contrast, the frog basilar papilla has the equivalent of inner hair cells, but lacks outer hair cells; it has no efferent system, and no basilar membrane. This suggests that the frog basilar papilla lacks some of the mechanical and neural feedback paths characteristic of the mammalian system. Detailed measurements of tuning curves, spontaneous activity and responses to tones an clicks reveal large parametric differences between frog and mammals in spontaneous rate, absolute refractory time, long-term adaptation and phase locking. Responses to tone bursts are qualitatively similar, but parametrically quite different. More focused examinations of these effects will be able to exploit the differences in adaptation to long- versus short-duration stimuli could be caused by depletion of afferent neurotransmitter or by activation of feedback loops involving the efferent system. In the basilar papilla, any differences in adaptation must result from changes in the afferent pathway alone. PMID- 2228800 TI - Potassium-induced release of an endogenous toxic activity for outer hair cells and auditory neurons in the cochlea: a new pathophysiological mechanism in Meniere's disease? AB - In Meniere's disease, the increase of extracellular potassium concentration in the perilymph is thought to play a key role in determining the progressive loss of cochlear hair cells. In this paper, we describe a serum-free culture preparation of hair cells from 5 day-old rat and report the release by the cochlea, in response to an increase of extracellular potassium concentration, of a cytotoxic activity active on hair cells and auditory neurons. The toxic activity is associated with low molecular weight (less than 10,000 Dalton) molecule(s) as revealed by ultrafiltration. Morphological studies performed on the organ of Corti incubated during 24 h in the presence of the cochlea-derived toxic activity (CTA), show that this factor is toxic for hair cells and not for supporting or surrounding cells. The release of CTA occurs both in the spiral ganglion and in the organ of Corti. We suggest that this cochlea-derived toxic activity may play an important role in the pathophysiology of the hearing loss that occurs during the progression of Meniere's disease. PMID- 2228801 TI - Quantitative assessment of the rat stria vascularis. AB - Stria vascularis tissues from standardized regions in the basal, middle and apical turns of the rat cochlear duct were assessed quantitatively. Strial width, number of marginal cells across the strial width, radial area, as well as the volume density of the different components of the stria vascularis were determined for each standardized region. Strial width, number of marginal cells across the strial width and the radial area were greatest in the basal region and least in the apical region of the cochlea. The volume density of intermediate cells and capillary space was statistically unchanged in the three examined regions of the stria vascularis. However, the volume density of marginal cells and that of basal cells were different between regions. The volume density of marginal cells was highest in the basal turn while the volume density of basal cells was greatest in the apical turn. An objective assessment of the response of the stria vascularis to environmental conditions can be made by kant of its cellular architecture, providing a means to compare the effects of various agents between animal models used to study human inner ear dysfunction. PMID- 2228802 TI - On the influence of acoustical probe impedance on evoked otoacoustic emissions. AB - Using two different probes representing different acoustical impedances, simultaneously evoked otoacoustic emissions, thresholds in quiet, and delayed evoked emissions were measured in the frequency region of 900 to 1100 Hz for one subject who has extremely large emissions at these frequencies. All data show that the sound pressure produced in the closed ear canal clearly depends on two contributions, that of the activity of the inner ear, and that of the acoustical impedance of the probe. These effects can be simulated in an analog model of peripheral preprocessing. PMID- 2228803 TI - The ototoxic mechanism of cisplatin. AB - The ototoxic mechanism of cisplatin was investigated. Potentiation of cisplatin ototoxicity by furosemide and amino-oxyacetic acid (AOAA) was observed. Substantial hearing loss in cisplatin-deafened animals was accompanied by normal values of the endocochlear potential and a reduction in the sensitivity of the 2f1-f2 distortion products. The loss in dB of the sensitivity of the distortion products correlated extremely well with the loss of the neural sensitivity in dB. There was also a relationship between the fractional reduction of the low frequency (1000 Hz) microphonic potential and hearing loss in dB. Iontophoresis of cisplatin into scala media resulting in the immediate loss of neural thresholds at the site of iontophoresis. It is concluded that cisplatin caused the hearing loss by blocking OHC transduction channels. PMID- 2228804 TI - Heterodyne interferometer measurements of the frequency response of the manubrium tip in cat. AB - A heterodyne interferometer proved to be a very accurate tool to measure amplitude and phase of the malleus response during acoustical stimulation. It was shown that to obtain equal accuracy in the acoustical pressure measurements, pressure response must be remeasured at short time intervals. At frequencies above 4 kHz various gross resonances are apparent on the frequency response curves. The resonances are, depending on the animal, more or less pronounced. As a result of the improved accuracy changes of the malleus vibration response with time could clearly be discriminated. These changes can be related to shifts in frequency of the position of these resonances. Comparison of experimental frequency response and lumped parameter model predictions from literature shows that these resonances are not present in the model responses. PMID- 2228806 TI - Carbachol-induced inositol phosphate formation during rat cochlea development. AB - The age related-intensity developmental pattern of the phosphoinositide breakdown, which leads to the formation of intracellular second messengers, was investigated in rat cochleas by measuring the accumulation of inositol phosphates induced by carbachol in the presence of LiCl. The accumulation of the phosphoinositide metabolites elicited by this muscarinic agonist is very low at post-natal day 1 and particularly large during the period between post-natal days 8 and 14 with a peak around day 12. In the 25-day-old rat cochlea, carbachol induced a 2-fold increase in inositol phosphates (IPs) accumulation, with respect to the basal control level. The apparent affinities of the carbachol-induced IPs responses are 49.6, 31.6 and 36.7 microM in cochleas of 12-, 16- and 25-day-old rats, respectively, thus suggesting that the specific developmental changes are rather due to a modification in the number of muscarinic cholinergic receptors than to alterations of the apparent affinity of carbachol for its receptors. This developmental pattern of carbachol-elicited IPs accumulation reveals a striking time coincidence with both the efferent synaptogenesis at the outer hair cells (OHCs) level and the period of increased sensitivity of OHCs to aminoglycoside toxicity. Phosphoinositide breakdown may, consequently, play a role in the maturation of OHCs and their efferent supply. In addition, the remaining IPs response measured at 25 post-natal days indicates that muscarinic agonist mediated IPs metabolism also occurs in mature cochlea, and might be involved in the regulation of OHCs motility. PMID- 2228805 TI - Periaqueductal gray influence on anteroventral cochlear nucleus unitary activity and naloxone effects. AB - The effect of periaqueductal gray (PAG) electrical stimulation on the response properties of auditory and 'spontaneously' firing units (abolished when the cochlea is destroyed) in the anteroventral cochlear nucleus (AVCN) was explored using extracellular recordings in acute guinea-pigs. Significant increases and decreases in firing rate were detected in both neuronal groups: only 4% of the sound-responding units were insensitive to PAG stimulation while the 'spontaneous' units showed significantly smaller changes in firing rate in response to PAG stimulation. The auditory AVCN neurons were categorized both by their sound post stimulus time (PST) histograms at their characteristic frequency (CF) and the changes in the probability of discharge after PAG stimulation while the tone burst was maintained constant. PAG was implicated in pain input modulation through enkephalin actions. Because enkephalins have been also observed at the CN level, a pharmacological approach administering naloxone was carried out. We observed that 1) naloxone abolished the unit discharge shifts observed after PAG stimulation and 2) when the drug was injected without PAG stimulation, it produced changes in the firing, increasing or decreasing, and shifts in the probability of discharge versus time, even in cases in which the firing rate was not altered. An involvement of the auditory efferent pathways to CN is postulated and a possible enkephalinergic factor is suggested as a modulator of the auditory input at this level. The probability of discharge observed in the PSTH at the AVCN is dependent on the auditory input plus the central efferent action to its neurons. PMID- 2228807 TI - Sensitivity for interaural time and intensity difference of auditory midbrain neurons in the grassfrog. AB - The sensitivity for interaural time (ITD) and intensity (IID) difference was investigated for single units in the auditory midbrain of the grassfrog. A temporally structured stimulus was used which was presented by means of a closed sound system. At best frequency (BF) the majority of units was selective for ITD as indicated by an asymmetrically (73%) or symmetrically (7%) shaped ITD-rate histogram. About 20% appeared to be nonselective. Units with a symmetrical rate histogram had BFs well above 0.9 kHz, whereas for the other categories no relationship with BF was observed. Most units had a selectivity for ITD which was rather independent from frequency and absolute intensity level. In 62% of the units interaural time difference could be traded by interaural intensity difference. In most cases this so-called time-intensity trading could be explained by the intensity-latency characteristics of auditory nerve fibres. About 20% was sensitive to IID only and 5% to ITD only. A binaural model is proposed which is based on the intensity-rate and intensity-latency characteristics of auditory nerve fibres, the linear summation of excitatory and inhibitory post synaptic potentials in second order neurons, and spatiotemporal integration at the level of third order neurons. By variation of only a small number of parameters, namely strengths and time constants of the connectivities, the range of experimentally observed response patterns could be reproduced. PMID- 2228808 TI - Reversible blockade of vestibular evoked activity in the chick. AB - Vestibular evoked potentials (VsEP) were recorded from young chickens following bilateral intralabyrinthine injections of Tetrodotoxin (TTX). The purpose of this study was to document the long term effects of TTX on the electrophysiological activity of the vestibular system. VsEP components were eliminated within 30 min of TTX injections. Twelve hours post-treatment the early waves of the response began to emerge from the background noise. Recordings completed 24 h after the manipulation were not different from baseline responses. Our results indicate that TTX is a useful substance for reversibly blocking vestibular afferent pathways without permanently damaging the labyrinth or neural components. In addition, VsEP is an appropriate tool to objectively evaluate vestibular system function. Their combination can be applied to study the significance of afferent influences on the development and function of vestibular nuclei. PMID- 2228809 TI - Women of Denmark. PMID- 2228810 TI - Maternal role of women in clerical jobs in southern Brazil: stress and satisfaction. AB - The number of women in the work force in Brazil is increasing, and a pattern of early work participation and a later decline continues to be manifested. The maternal role is a central role for these women. We investigated the quality of the maternal role as perceived by women who hold clerical jobs in a southern Brazilian city. Qualitative and quantitative data were collected from a random sample of 60 women. Thirty-three of these women were mothers with one or more children. Maternal role likes, dislikes, and stresses were obtained through questionnaires. Coping strategies and resources to cope with the maternal role needs were also obtained. Analytical categories were developed for each of these variables and the analysis was completed through the use of a qualitative computer program. PMID- 2228811 TI - Trying it on for size: mutual support in role transition for pregnant teens and student nurses. AB - Pregnant adolescents and student nurses are both undergoing role transition when student nurses teach prenatal classes to single adolescents. Through participant observation and the constant comparative analysis of grounded theory, I determined that both groups engage in the process of "trying it on for size". As learners teach learners, an environment of mutual support is created that allows for experimentation with roles. In this article, the process of trying it on for size is discussed from the perspective of a faculty advisor with emphasis on the benefits to both students and clients. PMID- 2228812 TI - Dimensions of nurse and patient roles in labor. AB - Nurses, as the principal caregivers during labor, play a major role in structuring the social context of childbirth. The influence of nurse-patient verbal interaction on the social construction of the childbirth experience was investigated. Verbatim records of nurse-patient interaction during labor were analyzed using Stiles's (1978a) Taxonomy of Verbal Response Modes. Nurse and patient scores on three dimensions of interpersonal roles, attentiveness, acquiescence, and presumptuousness, were determined. The results indicated that nurses established and maintained control over the definition of the childbirth experience. The viewpoint of the laboring woman was seldom acknowledged as relevant. Presumption of knowledge of the laboring woman's experience and failure to determine her perception of the situation can have a negative impact on individualization of care and the creation of a patient-centered birthing environment. PMID- 2228813 TI - Sleep and the reproductive cycle: a review. AB - Women of all ages have been found to have a higher rate of sleep disturbances than men. Attempts to determine whether hormonal changes marking their reproductive lives render women more vulnerable to emotional stress and to concomitant sleep disturbances are the focus of this article. Investigations of sleep patterns and sleep-related experiences that occur in connection with the menstrual cycle (normal menstrual cycle and premenstrual syndrome) and are associated with hormonal abnormalities (amenorrhea) and changes in hormonal status (pregnancy and menopause) are reviewed. Methodological problems are discussed and areas of future research are proposed. It is suggested that the triad of sleep, endocrine changes, and mood should be more systematically investigated. PMID- 2228815 TI - Early patterns of maternal attachment. AB - The relationship between maternal-fetal attachment and maternal-child interaction was examined. The Maternal Fetal Attachment Scale (Cranley, 1981) was administered to 32 women between their 35th and 40th weeks of pregnancy. These mothers were observed again while they fed their infants once on the second and once on the third postpartum days. Their interactive behaviors were then rated on the Nursing Child Assessment Feeding Scale (University of Washington) and the Funke Mother-Infant Interaction Assessment. The findings indicated a positive and significant relationship between maternal fetal attachment behaviors and mother infant interaction. Qualitative data collected during the research process gave meaning and interpretation to observed behaviors. Implications for nursing practice are discussed. PMID- 2228814 TI - Drug therapy in pregnancy: the lessons of diethylstilbestrol, thalidomide, and bendectin. AB - A pregnant woman and the fetus she carries face health risks from many sources. One risk that requires ongoing vigilance is the use of prescription drugs during pregnancy. The international health care community has been sensitized to the risks of drug use during pregnancy because of three pharmaceuticals that have caused widespread crises for mothers and their offspring. The crises that diethylstilbestrol, thalidomide, and, to a lesser extent, Bendectin have created in the past four decades are reviewed in this article. The lessons these drug crises can teach us are articulated in the belief that similar crises may be averted in the future. PMID- 2228816 TI - Enhancing the adolescent reproductive process: efforts to implement a program for black adolescent fathers. AB - The importance of adolescent fathers participating more fully in pregnancy and childrearing has been emphasized increasingly in the literature. This article describes the development and evaluation of childbearing clinical services designed for adolescent fathers. This multidisciplinary effort used an action research model that integrates empirical research into ongoing programs, continuously monitoring progress. It is comprised of five elements: population description, determination of clients' health needs, assessment and development of resources, evaluation of program services, and monitoring of outcomes. Although the study was not designed exclusively for black adolescents, 95% of the individuals who participated were black. The cultural composition of the study population suggests and impact on the findings. Suggestions are made for future program efforts with adolescent parents. PMID- 2228817 TI - Frequency of illness in mother-infant dyads. AB - The purpose of this study was to identify the frequency and types of illnesses experienced by mothers and their infants who were in the second half of the first year of life, the actions taken concerning these illnesses, the number of days the mother was hospitalized or in bed because of illness, and the subjective health status of both as rated by the mothers. During home visits mothers (N = 182) completed the Health Status Interview. They were asked about infant and maternal illness in the previous month and the actions taken in response to them. The number and types of illnesses reported indicate that mothers of full-term infants who were healthy at birth must deal with a number of minor illnesses in themselves and in their infants. The possible relationship of maternal illness to stress is discussed and suggestions are given for interventions by health professionals. PMID- 2228818 TI - Self-attitudes and behavioral characteristics of Type A and B female registered nurses. AB - Type A behavior in nurses has received little attention from researchers despite its assumed prevalence. What attitudes and behaviors distinguish Type A from Type B nurses? In this descriptive study, locus of control and selected self-attitudes of female RNs who exhibited the Type A pattern (n = 40) were compared with attitudes of Type B nurses (n = 40). The participants were selected from a larger sample of 178 RNs on the basis of extremely high and extremely low Type A scale scores. Type A nurses were more likely to term themselves "perfectionistic" or "compulsive" and to construe time as an enemy, in contrast to Type B nurses, who often referred to themselves as "easy-going." Self-aggrandizement characterized 73% of Type A nurses, as opposed to only 23% of Type Bs. As expected, Type A and B nurses differed significantly in terms of job involvement, speed/impatience, and hard-driving behaviors. Although it is widely recognized that the daily work of nurses subjects them to considerable physical and psychosocial stress, findings of this study suggest that a segment of RNs (Type As) may be at particular risk for coronary heart disease, burnout, and other health problems due to a constellation of attitudes and behaviors that they bring with them to the stressful work environment. Future research investigating the relationship of Type A/B characteristics and nursing turnover or burnout is recommended. PMID- 2228819 TI - Effects of a premenstrual syndrome education program on premenstrual symptomatology. AB - This exploratory study was conducted to determine the effects of an educational program on the number and severity of premenstrual symptoms as well as the number of premenstrual days with symptoms. Participants were a convenience sample of 47 employed women, whose scores on Abraham's Menstrual Symptomatology Questionnaire were in the moderate to severe range. Women were randomly divided into control and experimental groups, and those in the experimental groups participated in an education program. Both groups recorded daily on Abraham's Menstrual Symptom Diary for 19 anxiety, appetite, edema, and depression symptoms. Participants in the education program had fewer occurrences of anxiety and appetite symptoms and fewer severe edema and depression symptoms, as well as fewer days with symptoms, than women who did not participate in the educational program. The findings support the idea that client education can promote self-care and improve health status. PMID- 2228820 TI - Rural U.S. women: traditions and transitions affecting health care. AB - Warren (1972) proposed a means for determining differences between rural and urban social contexts that expands on the population definitions. Essentially, these differences are geographical, social, and economic in nature, and the health status of individuals in either setting may be affected by these variations. The health issues of women that evolve from these rural factors are the focus of this article. PMID- 2228822 TI - Local chemotherapy of selected bacterial infections of the ear. PMID- 2228821 TI - Epidemiology of antibiotic-inactivating enzymes and DNA probes: the problem of quantity. PMID- 2228823 TI - A comparative study on the inhibitory actions of chloramphenicol, thiamphenicol and some fluorinated derivatives. AB - Chloramphenicol, thiamphenicol and three fluorinated derivatives, Sch 24893, Sch 25298 and Sch 25393, were studied with respect to inhibition of the growth of selected bacterial strains and cell-free translation systems. Thiamphenicol was the least potent inhibitor in the former experiments, but behaved similarly to chloramphenicol and Sch 25298 in the latter, thereby displaying selective inhibition of prokaryotic protein synthesis. Thiamphenicol and Sch 25298 were shown to be like chloramphenicol in inhibiting peptidyl transferase activity specifically on 70 S ribosomes, but the antibiotics bound to their common ribosomal-receptor site with different efficiencies in the order chloramphenicol greater than thiamphenicol greater than Sch 25298. Selected bacterial strains highly resistant to chloramphenicol and thiamphenicol because of chloramphenicol acetyltransferase production were, in contrast, highly sensitive to inhibition by the fluorinated antibiotics. Thus Sch 24893, Sch 25298 and Sch 25393 may have important uses in veterinary and clinical medicine. PMID- 2228824 TI - In-vitro antibacterial activity of DQ-2556 and its stability to various beta lactamases. AB - DQ-2556, a new cephalosporin, showed a broad antibacterial spectrum over Gram positive and -negative organisms. The activity of DQ-2556 against recent clinical isolates of Gram-positive cocci and Enterobacteriaceae was comparable with that of cefpirome, and superior to that of ceftazidime. DQ-2556 was almost as active as cefpirome against Pseudomonas aeruginosa, but was less active than ceftazidime. With the exception of Ps. aeruginosa, DQ-2556 was bactericidal against various organisms at either the MIC or twice the MIC. DQ-2556 bound preferentially to penicillin-binding proteins (PBPs) 2, 1 and 3 of Staphylococcus aureus, PBPs 3, 1A and 1B of Escherichia coli and PBPs 1A, 3 and 4 of Ps. aeruginosa. DQ-2556 was stable to various penicillinases and cephalosporinases, but was unstable to oxyiminocephalosporinases. The Km values of DQ-2556 for the cephalosporinases of Citrobacter freundii and Enterobacter cloacae were only two- or three-fold higher than those of ceftazidime, indicating that DQ-2556 had a relatively high affinity for these enzymes compared with other recently developed cephalosporins. The MIC of DQ-2556 for Esch. coli increased four-fold in an OmpF deficient mutant, indicating that the OmpF porin was one of the major routes for penetration of DQ-2556 into Esch. coli cells. PMID- 2228825 TI - The effect of sodium salicylate on antibiotic susceptibility and synergy in Klebsiella pneumoniae. AB - Sodium salicylate was combined with the antibiotics amikacin, aztreonam, cefazolin, cefonicid, cefoperazone, ceftizoxime, norfloxacin, doxycycline, clindamycin, imipenem, mezlocillin and trimethoprim-sulphamethoxazole. The activity of the combinations was tested against encapsulated strains of Klebsiella pneumoniae, which differed markedly in their antibiotic susceptibility. The addition of salicylate (from 2 to 350 mg/l) to cultures increased the MIC of most antimicrobial agents from two- to four-fold, with the exception of imipenem and amikacin. Inhibition by imipenem was largely unchanged, and that of amikacin was increased in the presence of salicylate. The synergy of the combination of cefazolin and amikacin was abolished by salicylate, while the synergistic activity of imipenem and amikacin was significantly increased by salicylate. Doxycycline activity was most severely affected by salicylate as antimicrobial activity was significantly diminished at salicylate levels as low as 5 mg/l. In contrast, significant loss of inhibitory activity with other antimicrobials required at least 100 mg/l of salicylate. The clinical implications of salicylate on the sensitivity of K. pneumoniae to antimicrobials are discussed. PMID- 2228826 TI - In-vitro study of the susceptibility of cefoxitin/cefotetan resistant Bacteroides fragilis group strains to various other antimicrobial agents. AB - The in-vitro activity of various beta-lactam antibiotics, beta-lactam/beta lactamase inhibitor combinations, clindamycin, and metronidazole was determined against Bacteroides fragilis group isolates that were resistant to both cefoxitin and cefotetan. Among the cephalosporins tested ceftizoxime was the most active with 80% of the strains susceptible, followed by cefotaxime (65% susceptible), and cefoperazone (47% susceptible). Piperacillin and clindamycin showed comparable activity to ceftizoxime with 80% and 81% susceptible, respectively. The addition of a beta-lactamase inhibitor (sulbactam, clavulanate, or tazobactam) enhanced the activity of the various beta-lactam agents from 4-fold to 16-fold overall. One strain of B. fragilis was found that was resistant to all beta-lactam agents either alone or in combination. All strains in this study were susceptible to less than or equal to 4 mg/l of metronidazole. PMID- 2228827 TI - Beta-lactamase production, beta-lactam sensitivity and resistance to synergy with clavulanate of 737 Bacteroides fragilis group organisms from thirty-three US centres. AB - Beta-Lactamase production and agar dilution sensitivities to amoxycillin, amoxycillin/clavulanate, ticarcillin, ticarcillin/clavulanate, cefoxitin, imipenem and metronidazole were determined for 737 Bacteroides fragilis group strains isolated between 1986 and 1988 from 33 US centres. The strains comprised 441 B. fragilis, 114 B. thetaiotaomicron, 35 B. ovatus, 58 B. distasonis, 58 B. vulgatus, 26 B. uniformis and five B. caccae. Overall, addition of clavulanate lowered the geometric mean MICs of of amoxycillin from 46.7 to 0.6 mg/l, and of ticarcillin from 37.2 to 1.3 mg/l. Addition of clavulanate increased the number of strains sensitive to amoxycillin from 9.5% to 90.0%, and to ticarcillin from 68.0% to 98.6%. However, synergy was not observed following addition of clavulanate to amoxycillin and ticarcillin for 48 strains (6.5%). These comprised 15 B. fragilis, two B. ovatus, 21 B. distasonis, six B. vulgatus and four B. uniformis strains. Ten of the 15 non-synergic B. fragilis isolates had the features of B. fragilis homology group II and were susceptible to amoxycillin alone; the other five strains were resistant to amoxycillin and ticarcillin. Geometric mean MICs (% susceptibility) of the non-synergic strains were as follows: amoxycillin, 6.2 mg/l (68.8); amoxycillin/clavulanate, 4.8 mg/l (72.9); ticarcillin, 11.8 mg/l (75.0); ticarcillin/clavulanate, 9.4 mg/l (77.1). Twenty six strains (3.5% were resistant (greater than 32 mg/l) to cefoxitin, and two strains (0.3%) were resistant (4 mg/l) to imipenem. All were susceptible to metronidazole. Thus, on the basis of in-vitro activity, metronidazole, imipenem, ticarcillin/clavulanate, cefoxitin and amoxycillin/clavulanate are indicated for treatment of infections with B. fragilis strains. The clinical significance of the lack of synergy with clavulanate in the B. fragilis group is unclear; relatively low beta-lactam MICs for most of these strains suggests that they may be amenable to therapy with high doses of beta-lactams. Results of this study indicate that it cannot be assumed that clavulanate will uniformly inhibit beta lactamases in the B. fragilis group (especially B. distasonis) and indicate the need for identification and susceptibility testing, especially in cases of serious infections with these strains. PMID- 2228828 TI - Comparative in-vitro activities of ten fluoroquinolones and fusidic acid against Mycobacterium spp. AB - The in-vitro activities of eight new quinolones (A-56620, amifloxacin, difloxacin, CI-934, enoxacin, irloxacin, pefloxacin, temafloxacin), two reference fluoroquinolones (ciprofloxacin and ofloxacin) and fusidic acid against 147 mycobacterial strains, belonging to seven different species, were compared. Temafloxacin, ofloxacin and ciprofloxacin were the most active compounds. They only showed consistent activity against Mycobacterium tuberculosis, M. malmoense and M. fortuitum, but not against M. chelonei, M. avium, M. intracellulare and M. scrofulaceum. However, individual strains of these species were sometimes susceptible. The best overall in-vitro activity was obtained with temafloxacin, which often showed activity where other products were inactive. Fusidic acid merely displayed good activity against M. tuberculosis (MIC90 16 mg/l). PMID- 2228829 TI - The contribution of Escherichia coli to microbial colonization resistance. AB - The contribution of Escherichia coli to the microbial colonization resistance (CR) of the bowel was investigated in six healthy volunteers. Esch. coli was eliminated from faeces by the administration of a low dose (20 mg daily) of pefloxacin. This did not cause an increase in the faecal concentration of aerobic Gram-positive cocci or yeasts, nor did it facilitate colonization of the bowel by a pefloxacin-resistant challenge strain of Klebsiella pneumoniae. Therefore, Esch. coli does not appear to contribute to the microbial CR. After ten days of pefloxacin, clindamycin 300 mg was administered twice daily for 18 days. Clindamycin caused a significant increase in the faecal concentration of enterococci, yeasts and the K. pneumoniae challenge strain, indicating that the study design was suitable to demonstrate disturbance of microbial CR if it occurred. PMID- 2228830 TI - Effect of ceftazidime and gentamicin on the oropharyngeal and faecal flora of patients with haematological malignancies. AB - Thirty-four patients with haematological malignancies were studied to investigate the effect of empirical broad-spectrum antibiotic therapy (ceftazidime and gentamicin) on the gastro-intestinal flora. Twenty-five patients with acute myeloid leukaemia or post-autologous bone-marrow transplantation were given framycetin, nystatin and colistin (Fracon), and two patients with non-Hodgkin's Lymphoma were on co-trimoxazole, as long-term gut prophylaxis. Semi-quantitative microbiology was carried out on oropharyngeal swabs and quantitative microbiology on faecal specimens. The oropharyngeal flora consisted mainly of streptococci, coagulase-negative staphylococci and coryneforms, and was little affected by ceftazidime/gentamicin. A strain of Enterobacter cloacae resistant to ceftazidime and gentamicin colonized one patient, who later developed septicaemia. The faecal flora of patients on Fracon was dominated by enterococci; the few enterobacteria present were eliminated by ceftazidime/gentamicin. The anaerobic flora was absent in 15% of patients; in the remainder, it consisted mainly of Bacteroides spp., and was little affected by ceftazidime/gentamicin. The faecal flora of patients not on Fracon always contained anaerobes, and some strains of enterobacteria persisted throughout antibiotic treatment. None of the patients was colonized by Clostridium difficile or Pseudomonas aeruginosa. Broad-spectrum therapy with ceftazidime and gentamicin appeared to have little effect on the gastro intestinal flora, except to encourage the overgrowth of enterococci and reduce the numbers of enterobacteria. PMID- 2228831 TI - A three year survey of clinical isolates in the United Kingdom and their antimicrobial susceptibility. AB - A United Kingdom national survey of clinical isolates and their antimicrobial susceptibility was performed, with 61 participating hospital laboratories, between 1986 and 1989. Each centre used Microbe Base, a commercial suite of micro computer programs which can record and analyse antimicrobial susceptibility data Informative on 366,853 bacterial isolates and their antimicrobial susceptibility was received from hospital and domiciliary specimens; Candida spp. accounted for a further 9121 isolates. The sites of origin were urine 51%, skin and soft tissue 21%, lower respiratory tract 8%, genital tract 7%, ear, nose and throat 6%, eye 3%, blood 1.5% and faeces 1%. Gram-negative bacteria accounted for 242,307 isolates, the main species were Escherichia coli 48%, Proteus spp. 9%, Pseudomonas spp. 7%, Haemophilus influenzae 6% and Klebsiella spp. 4%. Gram positive bacteria numbered 124,546 with a predominance of Staphylococcus aureus 42%, beta-haemolytic streptococci 20%, Enterococcus spp. 12%, coagulase negative staphylococci 10% and Streptococcus pneumoniae 5%. All pneumococci were sensitive to penicillin, and methicillin resistant in Staph. aureus was only 2%. Twelve per cent of H. influenzae strains were resistant to ampicillin. There were no significant levels of gentamicin resistance in Gram-negative bacilli. PMID- 2228832 TI - 4-Quinolone resistant staphylococci. PMID- 2228833 TI - Susceptibility of enteropathogenic bacteria to furazolidone. PMID- 2228834 TI - Tetracycline resistance in Gardnerella vaginalis. PMID- 2228835 TI - Disc sensitivity testing to ofloxacin. PMID- 2228836 TI - Cefaclor in the treatment of chronic bronchitis. PMID- 2228837 TI - Successful treatment with chloramphenicol of Pseudomonas mesophilica peritonitis not responding to aztreonam and gentamicin. PMID- 2228838 TI - Serum protein binding and extravascular diffusion of methoxyimino cephalosporins. Time courses of free and total concentrations of cefotaxime and ceftriaxone in serum and pleural exudate. AB - A new approach to the study of the distribution pharmacokinetics of variably bound beta-lactams is to plot the concentration time course of their free (dialysable) and total (free and bound) forms. In the present study, the 6-h concentration time course was plotted of the total and free concentrations of cefotaxime and ceftriaxone in serum and pleural exudate in 12 patients per group, after iv dosing with 1 g of either cefotaxime or ceftriaxone. Samples were taken at 0.5, 1, 1.5, 2, 3, 4 and 6h after dosing. The results of a study of similar design, but conducted over 24 h in ten patients per group, following iv dosing with either cefotaxime 1 g 12-hourly or ceftriaxone 1 g daily are also reported. Samples were taken at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 14, 16 and 24 h after dosing. Areas under the curve of free cefotaxime in pleural fluid were greater than those of free ceftriaxone, in both the 6 h (+54.6%) and 24 h studies (+29.8% after 12 h and +71.0% after 24 h). The free cefotaxime/free ceftriaxone Cmax ratio was 1.75 in the 6 h study. Cefotaxime was superior to ceftriaxone in terms of the diffusion of the free (antibacterially active) fraction into a typical inflammatory exudate. Assessment of the effects of protein binding must be taken into account in antibiotic pharmacokinetic profiles. PMID- 2228839 TI - Tissue penetration of cefotaxime in normal pigs and pigs with haemorrhagic pancreatitis. AB - This study was designed to evaluate the tissue penetration of cefotaxime in normal pigs and pigs with haemorrhagic pancreatitis. Serum, peritoneal fluid, bile, gallbladder wall and pancreatic tissue concentrations of cefotaxime in these groups of pigs exceeded the MIC90 for susceptible species of Gram-negative aerobic bacteria. Cefotaxime penetration into pancreatic tissue and peritoneal fluid was increased from 2% to 2.6% and 73% to 89%, respectively, in pigs with pancreatitis in comparison with normal pigs. These increases however, were not statistically significant. PMID- 2228840 TI - An experimental model of chronic osteomyelitis caused by Escherichia coli treated with cefotaxime. AB - An experimental model in Wistar rats, of osteomyelitis caused by Escherichia coli, was used to evaluate the efficacy of cefotaxime in two treatment regimens of different durations. Four groups of rats were set up: a group of rats receiving short-term treatment (14 days) with subcutaneous cefotaxime (100 mg bd), killed after 56 days; a control group receiving no treatment, killed after 56 days; a group of rats undergoing long-term treatment (28 days) with subcutaneous cefotaxime as above, killed after 70 days and a control group of rats receiving no treatment, killed after 70 days. Analysis of histopathological and microbiological findings revealed significantly better results in the long term treatment group. No side-effects were observed during treatment or afterwards. PMID- 2228841 TI - Treatment of gonococcal conjunctivitis with a single intramuscular injection of cefotaxime. AB - Between 25% and 50% of children in African countries are exposed to Neisseria gonorrhoeae at birth and are at risk of developing gonococcal ophthalmia neonatorum. The problem is aggravated by the emergence of penicillinase-producing strains of N. gonorrhoeae (PPNG). Twenty-one children (9 boys, 12 girls, mean age 13 days) presenting with gonococcal conjunctivitis were identified during a 47 month period. Nineteen children received a single im injection of 100 mg/kg cefotaxime (maximum dose 1 g) without topical antibiotic therapy. One neonate with concurrent otitis media was treated with cefotaxime for five days and a 17 month old girl received two im injections because of the severity of her symptoms. Eight patients (38%) had received previous antibiotic therapy (penicillin im and/or tetracycline eye ointment). Twelve isolates of N. gonorrhoeae were found to be PPNG strains. At three to seven day follow-up examination all 21 patients were clinically cured without residual eye damage. Cefotaxime offers an effective first line treatment for gonococcal ophthalmia neonatorum in areas where there is a high prevalence of PPNG strains. The advantages of a single-dose treatment over multidose regimens in terms of compliance and cost are discussed. PMID- 2228842 TI - Short-course cefotaxime compared with five-day co-amoxyclav in acute otitis media in children. AB - This randomized, multicentre prospective study was undertaken to compare the efficacy and tolerance of a one day course of injectable cefotaxime with a five day oral course of co-amoxyclav (amoxycillin plus clavulanic acid) in the treatment of acute otitis media in children. The study was conducted in 116 patients between the ages of three months and 12 years. No significant difference in efficacy was observed between the two treatment groups, but tolerance to the treatments differed significantly. There were no unwanted side-effects in the cefotaxime group whereas 22% of children in the amoxycillin plus clavulanic acid group suffered side-effects (P 0.0007). Short-course antibiotic therapy with cefotaxime appears to be a valuable alternative to conventional treatment regimens for acute otitis media in children. PMID- 2228844 TI - Cefotaxime in the treatment of chronic osteomyelitis caused by gram-negative bacilli. AB - Fifty patients with chronic osteomyelitis due to aerobic or facultative Gram negative bacilli, alone or in mixed infections with Gram-positive cocci, were treated with cefotaxime. The diagnosis of osteomyelitis was made on the basis of clinical, roentgenographical, isotopic, microbiological and histopathological evidence of infection. Only those patients with infection sensitive to cefotaxime were treated. Most patients received 2 g cefotaxime qid iv for 30-60 days (mean 40 days). Some patients received metronidazole in addition. The following results were obtained at the six month follow-up: 40 patients cured, six improved, no failures and four relapses. The surgical technique had an impact on these results. No clinically important side-effects were encountered, nor were any cefotaxime resistant strains found. PMID- 2228843 TI - Comparison of cefotaxime, cefoxitin and clindamycin plus gentamicin in the treatment of uncomplicated and complicated pelvic inflammatory disease. AB - Patients with uncomplicated pelvic inflammatory disease (PID) (acute salpingitis and no pelvic masses) were randomly assigned for treatment with either cefotaxime or cefoxitin. A clinical cure was achieved in 17 of 20 cases (82%) and 19 of 22 cases (84%), respectively. Within the complicated PID group, patients were assigned to two subgroups: those with a tubo-ovarian complex (26 patients), and those with a tubo-ovarian abscess (32 patients), as confirmed by ultrasonography or surgery. Patients within each of these two subgroups were then randomly assigned for treatment with either cefotaxime or clindamycin plus gentamicin. Within the tubo-ovarian complex subgroup, a clinical cure was achieved in 11 of 13 cases (85%) treated with cefotaxime and 10 of 13 cases (77%) treated with clindamycin plus gentamicin. Within the tubo-ovarian abscess subgroup, a clinical cure was achieved in 12 of 16 cases (75%) treated with cefotaxime and 11 of 16 cases (69%) treated with clindamycin plus gentamicin. No differences in any category were statistically significant. Specimens for culture were obtained from the endocervix, endometrium, and when possible, the cul-de-sac, fallopian tubes, and abscess. Neisseria gonorrhoeae (33%) was isolated more frequently than Chlamydia trachomatis (12%) in patients with PID, and neither of these organisms was isolated with any increased frequency in patients with complicated PID. The majority of the patients were considered to have polymicrobial infection. Cefotaxime was as efficacious as cefoxitin and clindamycin plus gentamicin for the treatment of acute salpingitis, tubo-ovarian complex and tubo-ovarian abscess. PMID- 2228845 TI - Multiresistant Salmonella typhimurium systemic infection in Rwanda. Clinical features and treatment with cefotaxime. AB - Children with multiresistant Salmonella typhimurium (MRST) systemic infections, in total 246, were diagnosed during the study period. Of these, 220 had MRST without metastatic focal infections and 26 had metastatic focal infections (including 12 patients with meningitis). The median age of the children was 10 months. Diarrhoeal disease, measles and severe malnutrition were the most frequent causes of admission. Fever was found in 99% and diarrhoea in 72% of the patients, with respiratory symptoms in 72%. In 199 (81%) of the patients, the MRST infection was considered to be hospital-acquired. Of the 246 children, 159 were treated with cefotaxime. In this group, 16 of 152 patients died (10.5%). However, of the 87 children who did not receive cefotaxime, 64 died (74%). Relapses occurred in 4% of the patients with bacteraemia treated with cefotaxime. Our study confirms the high efficiency of cefotaxime in treating severe systemic infections with MRST. PMID- 2228846 TI - Prevention of bacterial colonization of the respiratory tract and stomach of mechanically ventilated patients by a novel regimen of selective decontamination in combination with initial systemic cefotaxime. AB - A novel regimen of selective decontamination (SDD) with initial systemic cefotaxime prevented bacterial colonization of the oropharynx and stomach in mechanically ventilated patients. In a three-group study of all patients receiving prolonged mechanical ventilation, patients in control groups A and B received antibiotics only when infection was present. In group A, antibiotics that disturb colonization resistance (CR) were used. In group B, antibiotics use was restricted to antibiotics not affecting CR. Patients in group C received SDD, consisting of norfloxacin, polymyxin E and amphotericin B, administered via a gastric tube and applied to the oropharynx. Group C patients further received an initial five day course of cefotaxime, 500 mg tid. The lower respiratory tract was colonized with microorganisms on admission in about half of the patients, and this persisted in both control groups. In group C, lower respiratory tract colonization was eliminated in all patients after five days. In both control groups about 90% of the patients acquired microbial colonization of the oropharynx and stomach, mostly with Gram-negative bacilli. In group C, only 12% and 24% of the patients acquired colonization of the oropharynx and stomach respectively (P less than 0.001). The oropharynx and stomach were the major sources of microorganisms causing lower respiratory tract infection in both control groups. In group C, elimination of oropharyngeal and gastric colonization completely prevented lower respiratory tract infection from these sources. PMID- 2228847 TI - Antibiotic prophylaxis with cefotaxime in endoscopic extraction of upper urinary tract stones: a randomized study. The Cefotaxime Cooperative Group. AB - This French multicentre, placebo-controlled, double-blind study investigated the efficacy of a single dose of cefotaxime 1 g iv in the prophylaxis of patients undergoing endoscopic extraction of urinary tract stones. Postoperative fever occurred in 12 patients in the placebo group and in nine in the cefotaxime group (no significant difference). The incidence of postoperative bacteriuria, between the first and third postoperative day, was significantly higher in the placebo group (15/60, 25%) than in the cefotaxime group (5/60, 8.5%). This controlled study clearly demonstrates the efficacy of antibiotic prophylaxis in endourological procedures. Cefotaxime significantly reduced the incidence of early postoperative bacteriuria without causing any significant side effects. PMID- 2228848 TI - Reflex control of the circulation during exercise: chemoreflexes and mechanoreflexes. AB - The overall scheme for control is as follows: central command sets basic patterns of cardiovascular effector activity, which is modulated via muscle chemo- and mechanoreflexes and arterial mechanoreflexes (baroreflexes) as appropriate error signals develop. A key question is whether the primary error corrected is a mismatch between blood flow and metabolism (a flow error that accumulates muscle metabolites that activate group III and IV chemosensitive muscle afferents) or a mismatch between cardiac output (CO) and vascular conductance [a blood pressure (BP) error] that activates the arterial baroreflex and raises BP. Reduction in muscle blood flow to a threshold for the muscle chemoreflex raises muscle metabolite concentration and reflexly raises BP by activating chemosensitive muscle afferents. In isometric exercise, sympathetic nervous activity (SNA) is increased mainly by muscle chemoreflex whereas central command raises heart rate (HR) and CO by vagal withdrawal. Cardiovascular control changes for dynamic exercise with large muscles. At exercise onset, central command increases HR by vagal withdrawal and "resets" the baroreflex to a higher BP. As long as vagal withdrawal can raise HR and CO rapidly so that BP rises quickly to its higher operating point, there is no mismatch between CO and vascular conductance (no BP error) and SNA does not increase. Increased SNA occurs at whatever HR (depending on species) exceeds the range of vagal withdrawal; the additional sympathetically mediated rise in CO needed to raise BP to its new operating point is slower and leads to a BP error. Sympathetic vasoconstriction is needed to complete the rise in BP. The baroreflex is essential for BP elevation at onset of exercise and for BP stabilization during mild exercise (subthreshold for chemoreflex), and it can oppose or magnify the chemoreflex when it is activated at higher work rates. Ultimately, when vascular conductance exceeds cardiac pumping capacity in the most severe exercise both chemoreflex and baroreflex must maintain BP by vasoconstricting active muscle. PMID- 2228849 TI - Effects of tracheal irritation and hypercapnia on tracheal smooth muscle in humans. AB - Both hypercapnia and tracheal irritation are known to constrict the airways in animals. To see whether similar responses occur in humans, we investigated tracheal smooth muscle (TSM) responses to hypercapnia and tracheal irritation with water in 14 paralyzed and anesthetized humans. TSM tone was monitored by measuring the pressure in the saline-filled cuff of the endotracheal tube. Although, tracheal irritation caused TSM constriction in 10 of 14 patients, 4 patients showed no TSM response. Administration of intravenous atropine attenuated the TSM constriction response. Hypercapnia did not cause any change in TSM tone in any of the 14 patients. These results indicate that in paralyzed and anesthetized humans, there exist interindividual differences in the TSM responses to tracheal irritation and that hypercapnia cannot be an effective stimulus for the TSM constriction. PMID- 2228850 TI - Mucus-depleted frog palate as a model for the study of mucociliary clearance. AB - To better understand the frog palate model of mucociliary transport, we measured the transport rate of mucus (MTR) from the leopard frog, Rana pipiens, and from the bullfrog, R. catesbeiana, recorded the stability of the MTR over a period of hours and days and over the course of 1 yr, and measured the viscoelasticity, percent solid composition, and spinnability (filance) of mucus from both species. Bullfrog mucus was less rigid than leopard frog mucus (log G* at 1 rad/s 2.09 vs. 2.61; P less than 0.01) and had a higher viscosity-to-elasticity ratio (tan delta at 1 rad/s 0.36 vs. 0.26; P less than 0.05). It also had a lower solids content (8.71 vs. 13.72%; P = 0.02), and there was a trend to lower spinnability for bullfrog mucus (filance 26.7 vs. 33.5 mm). These data suggest that bullfrog mucus has viscoelastic properties similar to normal mammalian respiratory mucus and leopard frog mucus has viscoelasticity similar to sputum samples. MTR was significantly slower in the winter than in the summer months (17 vs. 30 mm/min; P less than 0.0001). Although the leopard frog palate could be used for at least 7 consecutive days without exhaustion, bullfrog palates could be used for only 5 days. Palates of either species could generally be tested for 6 h/day without a significant decrease in MTR. These data clarify some of the sources of variability in the use of this system and suggest methods of standardization. PMID- 2228851 TI - Cerebral blood flow in acute mountain sickness. AB - Changes in cerebral blood flow (CBF) were measured using the radioactive xenon technique and were related to the development of acute mountain sickness (AMS). In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased at 24 h [45.1 to 55.9 initial slope index (ISI) units] and 4% increased at 6 days (47.1 ISI units). Four subjects had similar increases of CBF when ascending to 3,200 m 3 mo later, indicating the reproducibility of the measurements. In nine subjects, ascending from 3,200 to 4,785-5,430 m, CBF increased to 76.4 ISI units, 53% above estimated sea-level values. CBF and increases in CBF were similar in subjects with or without AMS. In six subjects, CBF was measured before and after therapeutic intervention. At 2 h CBF increased 22% (71.3 to 87.3 ISI units) above pretreatment values in three subjects given 1.5 g acetazolamide, while three subjects given placebo showed no change. Symptoms remained unaltered in all subjects during the 2 h of the study. Overall, the results indicated that increases in CBF were similar in subjects with or without AMS while acetazolamide provoked increases of CBF in AMS subjects caused no acute change in symptoms. Alterations in CBF cannot be directly implicated in the pathogenesis of AMS. PMID- 2228852 TI - Hydraulic conductivity of canine parietal pleura in vivo. AB - The hydraulic conductivity (Lp) of the parietal pleura was measured in vivo in spontaneously breathing anesthetized dogs in either the supine (n = 8) or the prone (n = 7) position and in an excised portion of the chest wall in which the pleura and its adjacent tissue were intact (n = 3). A capsule was glued to the exposed parietal pleura after the intercostal muscles were removed. The capsule was filled with either autologous plasma or isotonic saline. Transpleural fluid flow (V) was measured at several transpleural hydrostatic pressures (delta P) from the rate of meniscus movement within a graduated pipette connected to the capsule. Delta P was defined as the measured difference between capsule and pleural liquid pressures. The Lp of the parietal pleura was calculated from the slope of the line relating V to delta P by use of linear regression analysis. Lp in vivo averaged 1.36 X 10(-3) +/- 0.45 X 10(-3) (SD) ml.h-1.cmH2O-1.cm-2, regardless of whether the capsule was filled with plasma or saline and irrespective of body position. This value was not significantly different from that measured in the excised chest wall preparation (1.43 X 10(-3) +/- 1.1 X 10( 3) ml.h-1.cmH2O-1.cm-2). The parietal pleura offers little resistance to transpleural protein movement, because there was no observed difference between plasma and saline. We conclude that because the Lp for intact parietal pleura and extrapleural interstitium is approximately 100 times smaller than that previously measured in isolated stripped pleural preparations, removal of parietal pleural results in a damaged preparation. PMID- 2228853 TI - Fluctuation in timing of upper airway and chest wall inspiratory muscle activity in obstructive sleep apnea. AB - An imbalance in the amplitude of electrical activity of the upper airway and chest wall inspiratory muscles is associated with both collapse and reopening of the upper airway in obstructive sleep apnea (OSA). The purpose of this study was to examine whether timing of the phasic activity of these inspiratory muscles also was associated with changes in upper airway caliber in OSA. We hypothesized that activation of upper airway muscle phasic electrical activity before activation of the chest wall pump muscles would help preserve upper airway patency. In contrast, we anticipated that the reversal of this pattern with delayed activation of upper airway inspiratory muscles would be associated with upper airway narrowing or collapse. Therefore the timing and amplitude of midline transmandibular and costal margin moving time average (MTA) electromyogram (EMG) signals were analyzed from 58 apnea cycles in stage 2 sleep in six OSA patients. In 86% of the postapnea breaths analyzed the upper airway MTA peak activity preceded the chest wall peak activity. In 86% of the obstructed respiratory efforts the upper airway MTA peak activity followed the chest wall peak activity. The onset of phasic electrical activity followed this same pattern. During inspiratory efforts when phasic inspiratory EMG amplitude did not change from preapnea to apnea, the timing changes noted above occurred. Even within breaths the relative timing of the upper airway and chest wall electrical activities was closely associated with changes in the pressure-flow relationship. We conclude that the relative timing of inspiratory activity of the upper airway and chest wall inspiratory muscles fluctuates during sleep in OSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228854 TI - Prior running reduces hypertrophic growth of skeletal muscle grafts. AB - Run training can increase the mass of soleus muscle grafts, yet values remain lower than nongrafted muscle even with continued training. Thus we tested the hypothesis that nerve-implant soleus grafts of rats previously run trained would be refractory to the hypertrophic stimulus of ablation of synergistic muscle. We also compared the magnitude of growth of the nerve-implant soleus graft after ablation with that reported by others for the nerve-intact soleus graft. We studied eight groups that differed relative to the combination and order of treatments (running and ablation of synergistic muscle) and the graft age at the time of the ablation operation and study. Graft mass, protein concentration, and histochemical fiber composition were measured. Compared with grafts from cage sedentary rats, the mass and protein content of the nerve-implant soleus grafts were higher (16-63%) at all times after ablation. When the ablation operation was performed at 56 days postgrafting, there was a 33% increase in protein content of the soleus graft by 84 days for cage-sedentary animals. This increase was twofold greater (P less than or equal to 0.02) than the 15% increase that followed ablation for the grafts from the animals that had been run trained before the ablation operation. Four weeks of run training before the ablation operation impaired the adaptive response of muscle grafts to the ablation of synergistic muscles, which may reflect alterations in motor unit recruitment and/or satellite cell activity. Ablation of synergistic muscles resulted in an absolute growth of the nerve-implant soleus grafts that was comparable with that reported for nerve intact soleus grafts. PMID- 2228855 TI - Slow phase of transvascular fluid flux reviewed. AB - In six circuit experiments using a clinical hemofiltration device, we validated a colorimetric technique to measure transvascular volume exchange (VE). In 12 isolated excised canine left lower lobes, continuous colorimetric measurements of VE correlated well with calculations of VE from changes in microhematocrit obtained simultaneously. We introduced step increases in microvascular hydrostatic pressure (Pc) of 9 +/- 4.8 (SD) cmH2O and followed the time course of weight and continuous hematocrit changes measured colorimetrically for 40 min, after which Pc was returned to base line, while measurements were continuously obtained. This procedure was repeated for an additional 30 min. VE was calculated from the hematocrit signals and compared with the time course of the weight signal. After increases in Pc, followed by a rapid weight gain, weight signals followed a slow exponential time course, whereas the calculated VE changed linearly. VE reflected approximately 60% of the slow weight gain. When Pc was decreased, weight signals decreased exponentially, whereas VE continued to increase linearly at a slower rate. These results suggest that a significant component of the slow weight signal represents slow vascular volume changes. Contrary to what the weight signal suggested, edema was never reabsorbed over the range of Pc measured. PMID- 2228856 TI - Distribution of pulmonary capillary transit times in recruited networks. AB - When pulmonary blood flow is elevated, hypoxemia can occur in the fastest-moving erythrocytes if their transit times through the capillaries fall below the minimum time for complete oxygenation. This desaturation is more likely to occur if the distribution of capillary transit times about the mean is large. Increasing cardiac output is known to decrease mean pulmonary capillary transit time, but the effect on the distribution of transit times has not been reported. We measured the mean and variance of transit times in single pulmonary capillary networks in the dependent lung of anesthetized dogs by in vivo videofluorescence microscopy of a fluorescein dye bolus passing from an arteriole to a venule. When cardiac output increased from 2.9 to 9.9 l/min, mean capillary transit time decreased from 2.0 to 0.8 s. Because transit time variance decreased proportionately (relative dispersion remained constant), increasing cardiac output did not alter the heterogeneity of local capillary transit times in the lower lung where the capillary bed was nearly fully recruited. PMID- 2228857 TI - Catecholamines, circulation, and the kidney during water immersion in humans. AB - Because results in literature are discrepant with regard to the effects of water immersion (WI) on the release of norepinephrine (NE) in humans, the following study was performed. Simultaneous measurements of plasma NE, central cardiovascular variables, and renal sodium excretion were conducted in eight normal male subjects on 2 study days; 6 h of thermoneutral (35.0 degrees C) WI to the neck were preceded and followed by 1 h in the seated posture outside the water and 8 h of a seated control period. During the control period, the subjects wore a water-perfused garment (water temperature 34.6 degrees C) to obtain the same skin temperature as during WI. The subjects were fluid restricted overnight and kept in this condition throughout the study. Compared with the prestudy, post study, and control periods, plasma NE decreased significantly by 61% during WI. Simultaneously, central venous pressure, cardiac output, stroke volume, systolic arterial pressure, and arterial pulse pressure increased, whereas heart rate decreased. Renal sodium excretion and urine flow rate increased. In conclusion, the release of NE is suppressed in humans during immersion. This decrease probably reflects a decrease in sympathetic nervous activity initiated by stimulation of low- and high-pressure baroreceptors. It is possible that the decrease in NE acts as one of several mechanisms of the natriuresis and diuresis of immersion in humans. PMID- 2228858 TI - Effect of sleep and sleep deprivation on ventilatory response to bronchoconstriction. AB - To characterize ventilatory responses to bronchoconstriction during sleep and to assess the effect of prior sleep deprivation on ventilatory and arousal responses to bronchoconstriction, bronchoconstriction was induced in eight asthmatic subjects while they were awake, during normal sleep, and during sleep after a 36 h period of sleep deprivation. Each subject was bronchoconstricted with increasing concentrations of aerosolized methacholine while ventilatory patterns and lower airway resistance (Rla) were continually monitored. The asthmatic patients maintained their minute ventilation as Rla increased under all conditions, demonstrating a stable tidal volume with a mild increase in respiratory frequency. Inspiratory drive, as measured by occlusion pressure (P0.1), increased progressively and significantly as Rla increased under all conditions (slopes of P0.1 vs. Rla = 0.249, 0.112, and 0.154 for awake, normal sleep, and sleep after sleep deprivation, respectively, P less than 0.0006). Chemostimuli did not appear to contribute significantly to the observed increases in P0.1. Prior sleep deprivation had no effect on ventilatory and P0.1 responses to bronchoconstriction but did significantly raise the arousal threshold to induced bronchoconstriction. We conclude that ventilatory responses to bronchoconstriction, unlike extrinsic loading, are not imparied by the presence of sleep, nor are they chemically mediated. However, prior sleep deprivation does increase the subsequent arousal threshold. PMID- 2228859 TI - Rat soleus muscle ultrastructure after hindlimb suspension. AB - The aim of the present investigation was to determine, by quantitative electron microscopy, the effects of a 5-wk tail-suspension period on rat soleus muscle ultrastructure. A marked decline (-60%) in muscle mass occurred. The mean fiber cross-sectional area decreased to a greater extent (-75%) than the capillary-to fiber ratio (-37%), leading to a higher capillary density (+148%) after hypokinesia. The total mitochondrial volume density remained unchanged, whereas the volume density of myofibrils was slightly but significantly reduced (-6%). A shift from subsarcolemmal to interfibrillar mitochondria occurred. Interfibrillar mitochondrial volume density was highest near the fiber border and decreased toward the fiber center. An increase in volume density of satellite cells suggested muscle regenerative events. Soleus atrophy with tail suspension greatly decreases the muscular volume but leaves the ultrastructural composition of muscle fibers relatively unaffected. PMID- 2228860 TI - Linkage between parasternals and external intercostals during resting breathing. AB - To assess the mechanical coupling between the parasternal and external intercostals in the cranial portion of the rib cage, we measured the respiratory changes in length and the electromyograms of the two muscles in the same third or fourth intercostal space in 24 spontaneously breathing dogs. We found that 1) the amount of inspiratory shortening of the external intercostal was considerably smaller than the amount of shortening of the parasternal; 2) after selective denervation of the parasternal, the inspiratory shortening of both the parasternal and the external intercostal was almost abolished; 3) on the other hand, after selective denervation of the external intercostal, the inspiratory shortening of the parasternal was unchanged, and the inspiratory shortening of the external intercostal was reduced but not suppressed; and 4) this persistent shortening of the external intercostal was reversed into a clear-cut inspiratory lengthening when the parasternal was subsequently denervated. We conclude that in the dog 1) the inspiratory contraction of the external intercostals in the cranial portion of the rib cage is agonistic in nature as is the contraction of the parasternals; 2) during resting breathing, however, the changes in length of these external intercostals are largely determined by the action of the parasternals. These observations are consistent with the idea that in the dog, the parasternals play a larger role than the external intercostals in elevating the ribs during resting inspiration. PMID- 2228861 TI - Left ventricular asynchrony in patients with pulmonary hypertension. AB - Left ventricular regional wall motion was evaluated in 11 patients with pulmonary hypertension and 18 control subjects. All 11 patients had secondary pulmonary hypertension and less than 20% measured diameter stenosis in any vessel. This study utilizes a video-intensity-based frame-by-frame computerized technique. All pulmonary hypertensive patients showed early diastolic asynchrony in the anterior or apical regions that lasted 100-200 ms. The size of the abnormal area varied from 2 to 20% of the ventricular silhouette. Four patients also showed systolic abnormalities. No abnormalities were detected in the control group. The cause of the asynchrony detected in pulmonary hypertension is probably due to interventricular interaction caused by pressure gradients across the septum. PMID- 2228862 TI - Reactive absorption of nitrogen dioxide by pulmonary epithelial lining fluid. AB - In a previous study (J. Appl. Physiol. 68: 594-603, 1990) in isolated rat lungs, we suggested that the rate of pulmonary air space absorption of inhaled NO2 is limited, in part, by chemical reaction(s) rather than by physical solubility. Because the initial site of primary absorption interactions involves the epithelial lining fluid (ELF), we investigated whether ELF-NO2 interactions could account for pulmonary NO2 reactive absorption. Rat ELF, obtained by bronchoalveolar lavage (BAL), was compared with a model chemical system (reduced glutathione, GSH). In vitro exposures (NO2-air) used constant gas flow and planar gas-liquid interfaces. 1) Solvent pH notably altered NO2 uptake by GSH but to a lesser extent by BAL. 2) Uptake displayed [GSH]-dependent saturation. [ELF] in BAL was augmented by sequential lavage (lavagate reuse) of multiple lungs. Uptake was proportional to [ELF] but did not saturate under these exposure conditions. 3) The uptake rate exhibited [NO2] dependence. However, relative to increasing [NO2], fractional uptakes decreased for BAL and 1 mM GSH but not for 10 mM GSH. 4) Altered convective gas flow produced nonlinear increments in uptake (10 mM GSH) and substantial decrements in fractional uptake. 5) Arrhenius plots [ln(r) vs. 1/T, where r is reaction rate and T is absolute temperature (degree K)] for BAL and 1 mM GSH yielded respective activation energies of 4,952 and 4,149 kcal.g 1.mol-1 and degree of change in the rate of NO2 uptake per 10 degrees C (Q10) of 1.32 and 1.25. These results imply that the rate of NO2 uptake into rat ELF, like intact lung, is limited, in part, by chemical reaction(s).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228863 TI - Fractal properties of pulmonary blood flow: characterization of spatial heterogeneity. AB - The heterogeneity of pulmonary blood flow was examined using a fractal analytic procedure, and the results were compared with the traditional gravitational model of flow distribution. 99mTc-labeled macroaggregate was injected intravenously at functional residual capacity in six supine anesthetized dogs. The lungs were fixed in situ and sliced in transverse sections. The slices were imaged on a planar gamma camera, and a three-dimensional array of blood flow measurements was reconstructed for each lung. Fractal analysis was used to examine the spatial heterogeneity or RDs (relative dispersion = SD/mean) as a function of the number of pieces into which the flow array was subdivided. RDs was fractal and could be characterized by a fractal dimension (Ds) of 1.09 +/- 0.02, where a Ds of 1.0 reflects homogeneous flow and 1.5 indicates a random flow distribution. The data fit the fractal model exceptionally well with an average r = 0.98. RDs was examined in gravitational and isogravitational planes and as expected was greatest in the gravitational direction. However, the difference was small, suggesting that gravitation plays a secondary role to an underlying process producing heterogeneity. Within the limits of resolution attained by this study (piece volumes greater than 0.25 cm3), the heterogeneity of pulmonary blood flow is well characterized by a fractal model. PMID- 2228864 TI - Periodic flow at airway bifurcations. I. Development of steady pressure differences. AB - In studies of large-amplitude periodic flows at an airway bifurcation, we found an appreciable steady-state pressure difference between the terminal units. To elucidate the fluid dynamic origins of such steady-state pressure differences, we studied single asymmetric bifurcation models with various area ratios and branching angles. The daughter ducts were identical in size and were terminated into identical elastic loads. Sinusoidal flow oscillations were applied at the parent duct so that the upstream Reynolds number ranged from 30 to 77,000 and the Womersley parameter from 2 to 30. The steady-state component (time averaged) of the pressure measured at the terminal with the smaller branching angle was found to be consistently higher than that at the other terminal. This steady-state pressure difference scaled approximately as a fixed fraction of the parent duct dynamic head. Guided by the results of flow-visualization studies, we modeled such behavior based on the temporal and spatial differences of head loss between the two branches of the bifurcation. Our results suggest that interlobar heterogeneity of mean alveolar-pressure observed in excised canine lungs during high frequency oscillation (Allen et al., J. Appl. Physiol. 62: 223-228, 1987) arises solely from fluid dynamic origins: differential head loss due to asymmetry of central airway branching structure. PMID- 2228865 TI - Periodic flow at airway bifurcations. II. Flow partitioning. AB - The distribution of flow among parallel pathways is believed to be determined by the balance of downstream mechanical loads or time constants. We studied the influence of upstream flow conditions and airway geometry vs. downstream mechanical impedances in determining flow partitioning at airway bifurcations. Each model consisted of a single rigid bifurcation with various branching angles and area ratios but having identical pathway impedances. Sinusoidal volumetric oscillations were applied at the parent duct with various frequencies and tidal volumes. Measuring the terminal pressures continuously, we calculated the flow distribution. When flow amplitude was small, flow partitioning was homogeneous and synchronous, as expected in a system possessing homogeneous pathway impedances and time constants. But when flow amplitude was large and frequency was high, appreciable heterogeneity and asynchrony of flow partitioning arose; during midinspiration the high-velocity flow stream preferentially favored the axial pathway. This effect vanished in the absence of a net area change at the bifurcation. For a given bifurcation geometry, these observations could be organized using only two nondimensional parameters, neither of which incorporated consideration of fluid friction. The description of temporal events required, in addition, a nondimensional time. Therefore these flow-dependent phenomena and their underlying mechanisms differ fundamentally from those described in classical impedance models. The complex pattern of nonuniform interregional behaviors apparent in whole lungs when tidal volume and frequency are large (Allen et al., J. Clin. Invest. 76: 620-629, 1985) is reiterated faithfully in models consisting of only two compartments with homogeneous time constants. As such, the behaviors observed in lungs would appear to be attributable in large part to fluid dynamic factors in central airways. PMID- 2228866 TI - Periodic flow at airway bifurcations. III. Energy dissipation. AB - We measured the energy dissipation associated with large-amplitude periodic flow through airway bifurcation models. Each model consisted of a single asymmetric bifurcation with a different branching angle and area ratio, with each branch terminated into an identical elastic load. Sinusoidal volumetric oscillations were applied at the parent duct so that the upstream Reynolds number (Re) varied from 30 to 77,000 and the Womersley parameter (alpha) from 4 to 30. Pressures were measured continuously at the parent duct and at both terminals, and instantaneous branch flow rates were calculated. Time-averaged energy dissipation in the bifurcation was computed from an energy budget over a control volume integrated over a cycle and was expressed as a friction factor, F. We found that when tidal volume was small [ratio of tidal volume to resident (dead space) volume, VT/VD less than 1], F was independent of branching angle and fell with increasing alpha and VT/VD. When tidal volume was large (VT/VD greater than 1), F increased with increasing branching angle and varied less strongly with alpha and VT/VD. No simple benchmark flow represented the data well over the entire experimental range. This study demonstrates that only two nondimensional parameters, alpha and VT/VD, are necessary and are sufficient to describe time averaged energy dissipation in a given bifurcation geometry during sinusoidal flow. PMID- 2228867 TI - Maximal O2 uptake of in situ dog muscle during acute hypoxemia with constant perfusion. AB - We investigated the relationships among maximal O2 uptake (VO2max), effluent venous PO2 (PvO2), and calculated mean capillary PO2 (PCO2) in isolated dog gastrocnemius in situ as arterial PO2 (PaO2) was progressively reduced with muscle blood flow held constant. The hypothesis that VO2max is determined in part by peripheral tissue O2 diffusion predicts proportional declines in VO2max and PCO2 if the diffusing capacity of the muscle remains constant. The inspired O2 fraction was altered in each of six dogs to produce four different levels of PaO2 [22 +/- 2, 29 +/- 1, 38 +/- 1, and 79 +/- 4 (SE) Torr]. Muscle blood flow, with the circulation isolated, was held constant at 122 +/- 15 ml.100 g-1.min-1 while the muscle worked maximally (isometric twitches at 5-7 Hz) at each of the four different values of PaO2. Arterial and venous samples were taken to measure lactate, pH, PO2, PCO2, and muscle VO2. PCO2 was calculated using Fick's law of diffusion and a Bohr integration procedure. VO2max fell progressively (P less than 0.01) with decreasing PaO2. The decline in VO2max was proportional (R = 0.99) to the fall in both muscle PvO2 and calculated PCO2 while the calculated muscle diffusing capacity was not different among the four conditions. Fatigue developed more rapidly with lower PaO2, although lactate output from the muscle was not different among conditions. These results are consistent with the hypothesis that resistance to O2 diffusion in the peripheral tissue may be a principal determinant of VO2max. PMID- 2228868 TI - Lung overexpansion increases pulmonary microvascular protein permeability in young lambs. AB - To study the effects of inflation pressure and tidal volume (VT) on protein permeability in the neonatal pulmonary microcirculation, we measured lung vascular pressures, blood flow, lymph flow (QL), and concentrations of protein in lymph (L) and plasma (P) of 22 chronically catheterized lambs that received mechanical ventilation at various peak inflation pressures (PIP) and VT. Nine lambs were ventilated initially with a PIP of 19 +/- 1 cmH2O and a VT of 10 +/- 1 ml/kg for 2-4 h (base line), after which we overexpanded their lungs with a PIP of 58 +/- 3 cmH2O and a VT of 48 +/- 4 ml/kg for 4-8 h. QL increased from 2.1 +/- 0.4 to 13.9 +/- 5.0 ml/h. L/P did not change, but the ratio of albumin to globulin in lymph relative to the same ratio in plasma decreased, indicating altered protein sieving in the pulmonary microcirculation. Seven other lambs were mechanically ventilated for 2-4 h at a PIP of 34 +/- 1 cmH2O and a VT of 23 +/- 2 ml/kg (base line), after which their chest and abdomen were bound so that PIP increased to 54 +/- 1 cmH2O for 4-6 h without a change in VT. QL decreased on average from 2.8 +/- 0.6 to 1.9 +/- 0.3 ml/h (P = 0.08), and L/P was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228869 TI - Late-phase bronchial vascular responses in allergic sheep. AB - Sheep were classified on the basis of their airway response to Ascaris suum antigen aerosols as allergic or nonsensitive. Allergic sheep were classed as acute or dual responders. Acute responders had only an immediate increase in mean airflow resistance after antigen, whereas dual responders had an immediate and late-phase (6-8 h after antigen challenge) increase in mean airflow resistance; nonsensitive sheep had minimal airway responses to antigen (less than 30% increase from base line). The sheep were anesthetized 2 wk later and, after a left thoracotomy, were challenged with antigen to determine bronchial vascular responses; bronchial artery blood flow was measured with an electromagnetic flow probe. Airway responses to antigen aerosol challenge were similar in the anesthetized and conscious animals. The mean fall in bronchial vascular resistance (BVR) immediately after antigen challenge was similar in acute and dual responders (41 +/- 7 and 47 +/- 9% of base line, respectively). In dual responders, late-phase airway responses were preceded by a significant increase from base line in Qbr and a fall in bronchovascular resistance (BVR). The mean fall in BVR 6-8 h after antigen challenge in documented dual responders was significantly different from bronchial vascular responses in acute responders (59 +/- 3 vs. 89 +/- 10%, respectively). Sheep without airway responses to A. suum had no significant changes in bronchial hemodynamics or airways mechanics. Late phase-associated changes in BVR are a specific response to antigen challenge and may be a sensitive index of mediators being released.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228870 TI - Urinary N tau-methylimidazole acetic acid excretion in respiratory disease. AB - N tau-methylimidazole acetic acid (N tau-MIAA) is the principal urinary metabolite of histamine. The basal urinary excretion rate of N tau-MIAA was determined as 0.117 +/- 0.008 (SE) mg/h, with a renal clearance for N tau-MIAA of 273 +/- 27 ml/min implying active secretion. After subpharmacological infusion of histamine (50 ng.kg-1.min-1 over 2 h) in five volunteers that increased plasma histamine from 0.28 +/- 0.04 to 0.71 +/- 0.15 ng/ml, urinary excretion of N tau MIAA over 8 h was increased by less than 17% compared with a control saline infusion. Urinary N tau-MIAA excretion in normal controls (273 +/- 14 micrograms/mmol creatinine) was similar to that observed in patients with severe acute asthma (253 +/- 22 micrograms/mmol), antigen-induced bronchoconstriction (269 +/- 21 micrograms/mmol), seasonal allergic rhinitis (304 +/- 31 micrograms/mmol), and clinically stable bronchiectasis (270 +/- 22 micrograms/mmol). In contrast, large increases in metabolite excretion (greater than 7,000 micrograms/mmol creatinine) were observed in a patient with systemic mastocytosis where very high plasma histamine levels were recorded (greater than 500 ng/ml) and marked systemic hemodynamic effects occurred. We conclude that urinary N tau-MIAA will only be increased in pathologies where sustained hyperhistaminemia occurs and that increased local histamine production in the lung or the upper airway does not cause a measurable change in the basal urinary excretion of this metabolite. PMID- 2228871 TI - Effect of ischemia reperfusion or hypoxia reoxygenation on lung vascular permeability and resistance. AB - The effect of ischemia reperfusion or hypoxia reoxygenation on pulmonary vascular permeability and resistance was studied in 25 isolated blood-perfused dog lungs. Vascular permeability, assessed by determining filtration coefficient (Kf), and vascular resistances were measured at the beginning and end of the experiment. Ischemia reperfusion was produced by occluding blood flow to the lung for 3 h and reperfusing for 1 h, whereas hypoxia reoxygenation was obtained by ventilating the lung with 95% N2-5% CO2 for 3 h and then ventilating with 95% O2-5% CO2 for 1 h with no interruption of perfusion. There was a significant increase in Kf in both ischemia reperfusion and hypoxia reoxygenation groups (51 and 85%, respectively), and total vascular resistance increased greatly in both groups (386 and 532%, respectively). Two additional groups were also studied in which the ischemia reperfusion or hypoxia reoxygenation lungs were pretreated with allopurinol (20 micrograms/ml). The Kf did not significantly increase in either the allopurinol ischemia reperfusion or the allopurinol hypoxia reoxygenation groups (22 and 6%, respectively). However, total vascular resistance significantly increased in both groups (239 and 224%, respectively). Although vascular permeability is modestly increased by both ischemia reperfusion and hypoxia reoxygenation, the predominant change in these conditions is the increased vascular resistance, which predominantly affects the postcapillary resistance and would result in a greater tendency for edema to develop in these slightly damaged lungs. Allopurinol, which inhibits xanthine oxidase, attenuated the permeability changes in both groups and may be useful in preventing ischemia reperfusion injury in certain conditions. PMID- 2228872 TI - Plasma catecholamines in the aorta and the phrenicoabdominal vein in exercising dogs. AB - Plasma epinephrine and norepinephrine concentrations were measured in the aorta and phrenicoabdominal vein in five dogs at rest and during short-duration mild- and moderate-intensity exercise and during prolonged mild-intensity exercise. Plasma epinephrine and norepinephrine concentrations increased with exercise in both the aorta and the phrenicoabdominal vein. Plasma epinephrine concentration was much higher in the phrenicoabdominal vein than in the aorta (24-43 times). Plasma epinephrine concentrations in the aorta and phrenicoabdominal vein were significantly correlated (r = 0.88). This confirms that peripheral epinephrine concentration is a reliable index of the activity of the adrenal medulla during exercise. The epinephrine-to-norepinephrine ratio in the phrenicoabdominal vein was stable (4:1) throughout the experimental protocol, suggesting that the proportion of the two amines released by the adrenal medulla did not vary through this range of adrenal activity in dogs. PMID- 2228873 TI - Effect of saline infusion during exercise on thermal and circulatory regulations. AB - To quantify the effect of an acute increase in plasma volume (PV) on forearm blood flow (FBF), heart rate (HR), and esophageal temperature (Tes) during exercise, we studied six male volunteers who exercised on a cycle ergometer at 60% of maximal aerobic power for 50 min in a warm [(W), 30 degrees C, less than 30% relative humidity (rh)] or cool environment [(C), 22 degrees C, less than 30% rh] with isotonic saline infusion [Inf(+)] or without infusion [Inf(-)]. The infusion was performed at a constant rate of 0.29 ml.kg body wt-1.min-1 for 20-50 min of exercise to mimic fluid intake during exercise. PV decreased by approximately 5 ml/kg body wt within the first 10 min of exercise in all protocols. Therefore, PV in Inf(-) was maintained at the same reduced level by 50 min of exercise in both ambient temperatures, whereas PV in Inf(+) increased toward the preexercise level and recovered approximately 4.5 ml/kg body wt by 50 min in both temperatures. The restoration of PV during exercise suppressed the HR increase by 6 beats/min at 50 min of exercise in W; however, infusion had no effect on HR in C. In W, FBF in Inf(+) continued to increase linearly as Tes rose to 38.1 degrees C by the end of exercise, whereas FBF in Inf(-) plateaued when Tes reached approximately 37.7 degrees C. The infusion in C had only a minor effect on FBF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228874 TI - Transperitoneal fluid dynamics in rabbit liver. AB - The peritoneal cavity of 18 anesthetized spontaneously breathing supine rabbits was opened through a midline section. One or two hollow capsules (surface area 0.8 cm2) were glued to the exposed liver surface, filled with whole or 25% diluted plasma, and connected to a transducer and a graduated pipette. Various hydraulic pressures (Pcap) were set in the capsule; at each Pcap the liquid flow per unit surface area (V/S) between the Disse's interstitial space and the capsule was measured from the rate of liquid displacement in the pipette. The slope of the V/S vs. Pcap linear regression was utilized to estimate the hydraulic conductivity of the Glissonian-peritoneal membrane and averaged 5.1 x 10(-3) +/- 4.7 x 10(-3) (SD) ml.h-1.cmH2O-1.cm-2 (n = 25). Hydraulic pressure in the Disse's space (Pd) was measured by closing the capsule against the transducer disconnected from the pipette. At portal and hepatic venous pressures of 7.6 +/- 2.9 and 2.6 +/- 1 cmH2O, respectively, Pd was 2.05 +/- 2 cmH2O. Physiologically, Starling pressure gradients cause fluid transfer from the sinusoids to the Disse's space; transperitoneal fluid filtration only occurs through the liver surface that faces the diaphragm, which corresponds to one-fifth of the total hepatic surface. PMID- 2228875 TI - Nonrandom variability in respiratory cycle parameters of humans during stage 2 sleep. AB - We analyzed breath-to-breath inspiratory time (TI), expiratory time (TE), inspiratory volume (VI), and minute ventilation (Vm) from 11 normal subjects during stage 2 sleep. The analysis consisted of 1) fitting first- and second order autoregressive models (AR1 and AR2) and 2) obtaining the power spectra of the data by fast-Fourier transform. For the AR2 model, the only coefficients that were statistically different from zero were the average alpha 1 (a1) for TI, VI, and Vm (a1 = 0.19, 0.29, and 0.15, respectively). However, the power spectra of all parameters often exhibited peaks at low frequency (less than 0.2 cycles/breath) and/or at high frequency (greater than 0.2 cycles/breath), indicative of periodic oscillations. After accounting for the corrupting effects of added oscillations on the a1 estimates, we conclude that 1) breath-to-breath fluctuations of VI, and to a lesser extent TI and Vm, exhibit a first-order autoregressive structure such that fluctuations of each breath are positively correlated with those of immediately preceding breaths and 2) the correlated components of variability in TE are mostly due to discrete high- and/or low frequency oscillations with no underlying autoregressive structure. We propose that the autoregressive structure of VI, TI, and Vm during spontaneous breathing in stage 2 sleep may reflect either a central neural mechanism or the effects of noise in respiratory chemical feedback loops; the presence of low-frequency oscillations, seen more often in Vm, suggests possible instability in the chemical feedback loops. Mechanisms of high-frequency periodicities, seen more often in TE, are unknown. PMID- 2228876 TI - Phrenic afferent contribution to reflexes elicited by changes in diaphragm length. AB - Recent evidence from several laboratories suggests that activation of afferents in the diaphragm can reflexly affect inspiratory muscle activation. This study determined whether afferents in the diaphragm contribute to compensatory changes in phrenic motor drive when the operating length of the diaphragm is suddenly increased. Experiments were performed in six closed-chest pentothal-anesthetized cats. Length changes were measured using a pair of piezoelectric crystals implanted in the left crural diaphragm. The crural electromyogram (EMGdi) was measured by electrodes fixed to each crystal. The animal was suspended in a spinal frame, and a Plexiglas tube was fitted around the cat's abdomen. A balloon placed inside the tube was inflated during the expiratory phase to produce a mean increase of 17% in diaphragm length at functional residual capacity. Ten trials were performed in succession under the following conditions: intact, after bilateral vagotomy, after spinal section at C7, and after cervical dorsal rhizotomy. Peak integrated EMGdi (integral of EMGdi) and neural inspiratory time (nTI) were measured for the last control inspiration and the first after inflation. There was a significant reduction in the peak integral of EMGdi when the length of the diaphragm was increased for all conditions except after rhizotomy. Although not measured, it is likely that the tension developed by the diaphragm was also increased during abdominal compression. Results suggest that afferents sensitive to changes in the operating length and/or tension in the diaphragm contribute to compensatory alterations in phrenic motor drive. PMID- 2228877 TI - Regional metabolic differences in the rat diaphragm. AB - This study characterized the biochemical properties of the rat diaphragm by measuring the activities of selected citric acid cycle and glycolytic enzymes. The diaphragm was removed from 10 female Sprague-Dawley rats (180 days old) and dissected into five discrete anatomic regions: crural (region 1), left posterior costal (region 2), left anterior costal (region 3), right anterior costal (region 4), and right posterior costal (region 5). Sections were assayed for total protein concentration and the activities of succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH). The SDH activity in the crural region was approximately 18% lower (P less than 0.05) than that in any costal region. Furthermore, protein concentration was significantly lower (P less than 0.05) in the crural region compared with all costal regions. In contrast, costal regions 2 5 did not significantly differ from each other in protein concentration or SDH activity. LDH activity did not differ significantly (P greater than 0.05) between regions. Finally, the LDH-to-SDH activity ratio was significantly higher (P less than 0.05) in the crural diaphragm compared with all costal regions. We conclude that the crural region of the rat diaphragm is significantly lower in oxidative capacity than all the costal regions. Investigators who use a rodent model to study diaphragmatic function and plasticity should consider the oxidative heterogeneity of the diaphragm when designing experiments. PMID- 2228879 TI - Cardiovascular regulation during head-out water immersion exercise. AB - Head-out water immersion is known to increase cardiac filling pressure and volume in humans at rest. The purpose of the present study was to assess whether these alterations persist during dynamic exercise. Ten men performed upright cycling exercise on land and in water to the suprasternal notch at work loads corresponding to 40, 60, 80, and 100% maximal O2 consumption (VO2max). A Swan Ganz catheter was used to measure right atrial pressure (PAP), pulmonary arterial pressure (PAP), and cardiac index (CI). Left ventricular end-diastolic (LVED) and end-systolic (LVES) volume indexes were assessed with echocardiography. VO2max did not differ between land and water. RAP, PAP, CI, stroke index, and LVED and LVES volume indexes were significantly greater (P less than 0.05) during exercise in water than on land. Stroke index did not change significantly from rest to exercise in water but increased (P less than 0.05) on land. Arterial systolic blood pressure did not differ between land and water at rest or during exercise. Heart rates were significantly lower (P less than 0.05) in water only during the two highest work intensities. The results indicate that indexes of cardiac preload are greater during exercise in water than on land. PMID- 2228878 TI - Effect of increased central blood volume with water immersion on plasma catecholamines during exercise. AB - To examine the influence of an increase in central blood volume with head-out water immersion (WI) on the sympathoadrenal response to graded dynamic exercise, nine healthy men underwent upright leg cycle exercise on land and with WI. Plasma norepinephrine and epinephrine concentrations were used as indexes of overall sympathoadrenal activity. Oxygen consumption (VO2), heart rate, systolic blood pressure, and plasma concentrations of norepinephrine, epinephrine, and lactate were determined at work loads corresponding to approximately 40, 60, 80, and 100% peak VO2. Peak VO2 did not differ on land and with WI. Plasma norepinephrine concentration was reduced (P less than 0.05) at 80 and 100% peak VO2 with WI and on land, respectively. Plasma epinephrine and lactate concentrations were similar on land and with WI at the three submaximal work stages, but both were reduced (P less than 0.05) at peak exertion with WI. Heart rate was lower (P less than 0.05) at the three highest work intensities with WI. These results suggest that the central shift in blood volume with WI reduces the sympathoadrenal response to high-intensity dynamic exercise. PMID- 2228880 TI - Pharmacological differentiation of epithelium-derived relaxing factor from nitric oxide. AB - We examined the possibility that nitric oxide is one of the epithelium-derived relaxing factors in guinea pig airways. First we studied whether nitric oxide could relax isolated tracheal strips, and then we examined the effects of known inhibitors of endothelium-dependent relaxation (EDR) in the vascular system [hemoglobin, methylene blue, and NG-monomethyl-L-arginine (L-NMMA)] on epithelium dependent relaxation (EpDR) induced by hyperosmotic stimuli in perfused whole tracheal preparations. Mannitol (160 mM in Krebs-Henseleit solution) applied to the epithelial surface was used as an osmotic stimulus to induce EpDR after carbachol-induced contraction (2 microM, serosal side). Nitric oxide produced concentration-dependent and complete relaxation of epithelium-denuded tracheal strips. Preincubation of the whole trachea with hemoglobin significantly inhibited osmotic-induced EpDR (P less than 0.05), but preincubation with methylene blue and L-NMMA did not. Hemoglobin introduced into the epithelial side after EpDR induced by hyperosmotic stimuli reversed relaxation, but methylene blue and L-NMMA did not. These results suggest that, although EpDR and vascular EDR have some pharmacological similarities and nitric oxide can relax airway smooth muscle, nitric oxide is not responsible for osmotic-induced EpDR. PMID- 2228881 TI - Cardiovascular responses to arm cranking and FNS-induced leg exercise in paraplegics. AB - Twelve spinal cord-injured males performed arm-crank exercise (ACE) with and without concurrent functional neuromuscular stimulation (FNS) of paralyzed leg muscles to investigate the hypothesis that FNS would augment cardiovascular performance during submaximal ACE. Six men who exhibited vigorous isometric contractions of thigh and calf muscles were classed as "responders" to FNS (R), and the remaining subjects with poor or nonexistent contractions served as "nonresponder controls" (C). Steady-state heart rate and oxygen uptake during ACE at 30, 60, and 90 W were not appreciably different from the ACE + FNS condition. However, cardiac outputs in R were augmented by 30% during FNS at rest (from 4.9 to 6.4 l/min), by 18% during 30-W ACE + FNS (from 8.6 to 10.1 l/min), and by 28% during 90-W ACE + FNS (from 12.1 to 15.6 l/min). Similarly, resting stroke volumes were increased by 18% (9 ml) and by 23% (19 ml) at 60 W during FNS in the R group. Calculated total peripheral resistance was reduced at rest and during 90 W ACE + FNS by approximately 24%. In contrast, no alterations of circulatory hemodynamics were observed for C subjects. These data indicate that FNS-induced contractions of paralyzed leg muscles augment venous return to aid central cardiovascular control during upper-body submaximal exercise in paraplegics. PMID- 2228882 TI - Ventilatory control during exercise with increased respiratory dead space in goats. AB - Our objectives were to determine 1) the effects of increased respiratory dead space (VD) on the ventilatory response to exercise and 2) whether changes in the ventilatory response are due to changes in chemoreceptor feedback (rest to exercise) vs. changes in the feedforward exercise stimulus. Steady-state ventilation (VI) and arterial blood gas responses to mild or moderate hyperoxic exercise in goats were compared with and without increased VD. Responses were compared using a simple mathematical model with the following assumptions: 1) steady state, 2) linear CO2 chemoreceptor feedback, 3) linear feedforward exercise stimulus proportional to CO2 production (VCO2) and characterized by an exercise gain (Gex), and 4) additive exercise stimulus and CO2 feedback producing the system gain (Gsys = delta VI/delta VCO2). Model predictions at constant Gex [assuming VD-to-tidal volume (VT) ratio independent of VCO2] are that increased VD/VT will 1) increase arterial PCO2 (PaCO2) and VI at rest and 2) increase Gsys via changes in chemoreceptor feedback due to a small increase in the PaCO2 vs. VCO2 slope. Experimental results indicate that increased VD increased VD/VT, PaCO2, and VI at rest and increased Gsys during exercise. However, measurable changes in the PaCO2 vs. VCO2 slope occurred only at high VD/VT or running speeds. Gex was estimated at each VD for each goat by using the model in conjunction with experimental measurements. With 0.2 liter VD, Gex increased 40% (P less than 0.01); with 0.6 liter VD, Gex increased 110% between 0 and 2.4 km/h and 5% grade (P less than 0.01) but not between 2.4 and 4.8 km/h. Thus, Gex is increased by VD through a limited range. In goats, increases in Gsys with increased VD result from increases in both Gex and CO2 chemoreceptor feedback. These results are consistent with other experimental treatments that increase the exercise ventilatory response, maintaining constant relative PaCO2 regulation, and suggest that a common mechanism linked to resting ventilatory drive modulates Gex. PMID- 2228883 TI - Two discharge patterns of carotid body chemoreceptors in the goat. AB - Twenty-nine single carotid body chemoreceptor units recorded during normocapnic normoxia from 20 anesthetized goats were classified into two groups by discharge pattern. Thirteen fibers, which had interspike interval distributions with a prominent peak [24.0 +/- 9.8% (SD)] at 0- to 20-ms bin, were termed bursting fibers (BF). The 16 remaining fibers were termed nonbursting fibers (NBF); these had no notable peak in the interval distributions. During hypoxia and hypercapnia, the chemoreceptor fibers continued to discharge in their established patterns. The interval distribution of most NBF spike trains could be described with the Poisson process, but none of the BF could be. However, except for the intervals in the range of 0-20 ms, the interval distribution of the BF could be described as exponential. This study suggests that 1) there are two distinct populations of the goat chemoreceptor fiber, each with an inherent discharge pattern; 2) the chemoreceptor did not code information about arterial PO2 and PCO2 in different patterns; and 3) the basic chemotransduction mechanism is likely the same in BF and NBF, and the difference in discharge pattern is more likely to reflect processes downstream from the transducer. PMID- 2228884 TI - Increased fatigue of isovelocity vs. isometric contractions of canine diaphragm. AB - A comparison of fatigue as a loss of force with repeated contractions over time was performed in canine respiratory muscle by isometric (nonshortening) and isovelocity (shortening) contractions. In situ diaphragm muscle strips were attached to a linear ergometer and electrically stimulated (30 or 40 Hz) via the left phrenic nerve to produce either isometric (n = 12) or isovelocity (n = 12) contractions (1.5 s) from optimal muscle length (Lo = 8.8 cm). Similar velocities of shortening between isovelocity experiments [0.19 +/- 0.02 (SD) Lo/S] were produced by maximizing the mean power output (Wmax = 210 +/- 27 mW/cm2) that could be developed over 1.5 s when displacement was approximately 0.30 Lo. Initial peak isometric tension was 1.98 kg/cm2, whereas initial peak isovelocity tension was 1.84 kg/mc2 (P less than 0.01) or 93% of initial isometric tension. Fatigue trials of 5 min were conducted on muscles contracting at a constant duty cycle (0.43). At the end of the trials, peak isovelocity tension had fallen to 50% of initial isometric tension (P less than 0.01), whereas peak isometric tension had only fallen by 27%. These results indicate that muscle shortening during force production has a significant influence on diaphragm muscle fatigue. We conclude that the effects of shortening on fatigue must be considered in models of respiratory muscle function, because these muscles typically shorten during breathing. PMID- 2228885 TI - Measurement of phase I volume breath by breath in spontaneously breathing guinea pigs. AB - A new method to determine phase I volume in tracheotomized spontaneously breathing guinea pigs is presented. Measurements were performed in three animals weighing 567-896 g. In simultaneous tracings of tidal volume (VT) and expiratory profiles of endogenous gases (PO2 or PCO2), the phase I volume of each breath was determined graphically as the volume expired up to the end of phase I of the expirogram. The mean phase I volume of different animals ranged from 0.29 to 0.43 ml with an arithmetic dispersion between 0.014 and 0.021 ml. Spontaneous sighs sometimes with doubling of the VT caused a significant rise of phase I volume up to 50% of the normal values. The linear regression curve was calculated for corresponding VT's and phase I volumes. The VT gradient of the phase I volume as the slope of this curve ranged from 0.108 to 0.217 ml/ml VT. The results of the new procedure, which works also with humans and rabbits, are discussed in respect to improvement of the characterization of the bronchial system. Compared with the human system, the VT gradient of the guinea pig is four times greater. By not being affected by disorders in pulmonary gas exchange, the phase I volume determined as described is a new suitable quantity to specifically assess actions and reactions of the bronchial system. PMID- 2228887 TI - Sensitivity analysis of respiratory parameter uncertainties: impact of criterion function form and constraints. AB - A sensitivity analysis based on weighted least-squares regression is presented to evaluate alternative methods for fitting lumped-parameter models to respiratory impedance data. The goal is to maintain parameter accuracy simultaneously with practical experiment design. The analysis focuses on predicting parameter uncertainties using a linearized approximation for joint confidence regions. Applications are with four-element parallel and viscoelastic models for 0.125- to 4-Hz data and a six-element model with separate tissue and airway properties for input and transfer impedance data from 2-64 Hz. The criterion function form was evaluated by comparing parameter uncertainties when data are fit as magnitude and phase, dynamic resistance and compliance, or real and imaginary parts of input impedance. The proper choice of weighting can make all three criterion variables comparable. For the six-element model, parameter uncertainties were predicted when both input impedance and transfer impedance are acquired and fit simultaneously. A fit to both data sets from 4 to 64 Hz could reduce parameter estimate uncertainties considerably from those achievable by fitting either alone. For the four-element models, use of an independent, but noisy, measure of static compliance was assessed as a constraint on model parameters. This may allow acceptable parameter uncertainties for a minimum frequency of 0.275-0.375 Hz rather than 0.125 Hz. This reduces data acquisition requirements from a 16- to a 5.33- to 8-s breath holding period. These results are approximations, and the impact of using the linearized approximation for the confidence regions is discussed. PMID- 2228886 TI - Spatial distribution of collagen and elastin fibers in the lungs. AB - Surface tension forces acting on the thin-wall alveolar septa and the collagen elastin fiber network are major factors in lung parenchymal micromechanics. Quantitative serial section analysis and morphometric evaluations of planar sections were used to determine the spatial location of collagen and elastin fibers in Sprague-Dawley rat and normal human lung samples. A large concentration of connective tissue fibers was located in the alveolar duct wall in both species. For rats, the tissue densities of collagen and elastin fibers located within 10 microns of an alveolar duct were 13 and 9%, respectively. In human lung samples, the tissue densities of collagen and elastin fibers within 20 microns of an alveolar duct were 18 and 16%, respectively. In both species, bands of elastin fibers formed a continuous ring around each alveolar mouth. In human lungs, elastin fibers were found to penetrate significantly deeper into alveolar septal walls than they did in rat lungs. The concentration of connective tissue elements in the alveolar duct walls of both species is consistent with their proposed roles as the principal load-bearing elements of the lung parenchyma. PMID- 2228888 TI - Errors in heat flux measurements due to the thermal resistance of heat flux disks. AB - Questions have been raised regarding the effect of the thermal resistance of heat flux transducers (HFTs) on the thermal flux from the skin. A model capable of simulating a large range of "tissue" insulation (variable-R model) was used to study the effect of the underlying tissue insulation on the relative error in heat flux due to the thermal resistance of the HFTs. The data show that the deviation from the true value of heat flux increases as the insulation of the underlying tissue decreases (r = 0.99, P less than 0.001). The underestimation of the heat flux through the skin measured by an HFT is minimal when the device is used on vasoconstricted skin in cool subjects (3-13% error) but becomes important when used during vasodilation in warm subjects (29-35% error) and even more important on metallic-skin mannequins (greater than 60% error). PMID- 2228889 TI - Central nervous effects of CRF and angiotensin II on cardiac output in conscious rats. AB - Studies were performed to determine whether the central nervous system actions of corticotropin-releasing factor (CRF) and angiotensin II (ANG II) on systemic arterial pressure are mediated, in part, through changes in cardiac output (CO). Changes in CO after intracerebroventricular administration of ANG II and CRF were assessed in conscious unrestrained rats bearing pulsed Doppler flow probes on the ascending aorta. Intracerebroventricular injection of CRF (0.15 nmol) increased arterial pressure (15-20 mmHg), heart rate (70-100 beats/min), and CO (25-35%) without significantly affecting total peripheral resistance. Intracerebroventricular injection of ANG II (0.1 nmol) produced similar elevations of arterial pressure (15-20 mmHg). However, the ANG II-induced pressor response was attended by significant decreases in heart rate (20 beats/min) and CO (10-15%) and significant increases in total peripheral resistance (30-40%). The results of these studies demonstrate that CO, as assessed by pulsed Doppler flow probe methodology, may be influenced significantly and differentially by central nervous system administration of CRF and ANG II. PMID- 2228890 TI - Coping, negative affectivity, and the work environment: additive and interactive predictors of mental health. AB - The present study tested the hypothesis that direct coping would moderate relations between work stress and mental health outcome, whereas suppression (a form of emotion-focused coping) would show an overall effect on outcome. Data on coping, perceived work demand and support, and affective symptoms were obtained from trainee teachers (N = 157). The results supported the hypothesis. Gender differences also were observed; men reported more use of suppression than did women. In addition, negative affectivity (NA) was examined as a confounding variable and as an index of reactivity in stress-outcome relations. NA acted to inflate associations between work perceptions and affective symptoms, but it was also a significant moderator variable; high NA subjects showed greater reactivity to work demand than did low NA subjects. PMID- 2228891 TI - Some methodological considerations for the behavioral genetic analysis of work attitudes. AB - In a recent article, Arvey, Bouchard, Segal, and Abraham (1989) argued that about 30% of the variance in job satisfaction was accounted for by workers' genetic make-ups. To demonstrate this, they examined a group of monozygotic twins who had been reared apart. Although this method has been used widely in behavioral genetic research, it contains many hidden threats to validity, which could render suspect numerical estimates of either environmental or genetic effects. We examine some of the threats associated with this type of twin research, emphasizing the problems involved in quantifying the heritability of job satisfaction. PMID- 2228892 TI - Examining the relationships among self-report measures of the Type A behavior pattern: the effects of dimensionality, measurement error, and differences in underlying constructs. AB - The most widely used self-report measures of the Type A behavior pattern (TABP) are the Bortner scale, the Framingham scale, and the Jenkins Activity Survey (JAS). Though high scores on each of these measures have been linked to the development of coronary heart disease, their intercorrelations are rather low, suggesting that they may reflect different aspects of TABP. This study indicates that the low correlations among the Bortner scale, the Framingham scale, and the JAS are due not only to differences in underlying constructs but also to measurement error and multidimensionality. These results also identify several psychometric problems, which raise serious questions regarding the use of these measures in TABP research. Suggestions for the development of new measures of TABP are offered. PMID- 2228894 TI - Childhood acute lymphoblastic leukemia--Part I. Biology of the lymphoblast. PMID- 2228893 TI - Morphologic and cytochemical characteristics of childhood lymphoblastic leukemia. AB - The majority of childhood acute leukemias can be classified as acute lymphoblastic leukemia and acute nonlymphocytic leukemia with light microscopy and cytochemical stains alone. However, myeloperoxidase-negative myeloblastic leukemias and megakaryoblastic leukemias, as well as some metastatic tumors, can mimic lymphoblastic leukemia when these cytologic examinations are used. Conversely, occasional cases of Sudan black B-positive ALL can be confused with myeloblastic leukemia. Thus, additional immunologic and sometimes further ultrastructural studies should complement the morphologic diagnosis of ALL. The significance of L1 and L2 subtypes of ALL is still controversial. Modern chemotherapy may have obscured any significance of this division. Future studies of lymphoblast morphology should center on biologic correlates of the L2 cytology. Little prognostic significance has been found for the morphologic variants of ALL, such as the granular and hand-mirror cell types. It is important not to confuse granular ALL with acute myeloblastic leukemia. Functional immunologic studies may help in delineating the cause of uropod formation in hand mirror variant ALL. PMID- 2228895 TI - Immunologic markers in childhood acute lymphoblastic leukemia. AB - This article details the immunologic diversity of acute lymphoblastic leukemia in children. A historical review of developments in immunophenotyping is followed by a discussion of how major subgroups of leukemia are best defined today. The relationship of immunologic subtypes to stages of normal lymphoid development is explored, and the clinical impact of immunophenotyping is discussed. PMID- 2228896 TI - Mixed-lineage leukemia and asynchronous antigen expression. AB - Considerable confusion exists regarding the definition of acute mixed-lineage leukemia. We have proposed a list of strict criteria, limiting the term acute mixed-lineage leukemia to those patients whose blast cells co-express lymphoid and myeloid characteristics. This system includes cytochemical, immunologic, molecular, and cytogenetic characteristics that are strongly associated with either lymphoid or myeloid lineages. As more information becomes available, the criteria for mixed-lineage leukemia will undoubtedly change. Identification of patients with mixed-lineage leukemia and metachronous leukemia (lineage switch) is important for determining the prognostic implications of these findings. Care must be taken in identifying cases of metachronous leukemia because of the increased incidence of second malignancies following aggressive therapy. Evidence of a recurrence of the original clone must be obtained before metachronous leukemia can be diagnosed. As with mixed-lineage and metachronous leukemias, the potential clinical and prognostic implications of lymphoid leukemias with antigenic asynchrony should be identified. The asynchronous antigen expression in leukemic lymphoblasts may provide a means for detecting minimal residual disease. Detection of minimal residual leukemia is possible because these blasts differ from the predominant population of normal lymphoid cells in their expression of cell surface markers. Study of the mechanisms that lead to these unusual leukemias may result in better understanding of the processes that underlie both normal hematopoietic differentiation and leukemogenesis. An understanding of these leukemias may also permit identification of cases that are destined to fail current therapies so that more intensive or selective therapy can be instituted for such children. Curing the 30% of children with ALL that relapse despite our best efforts should be one of the top priorities for pediatric oncologists. PMID- 2228897 TI - Cytogenetic abnormalities and molecular markers of acute lymphoblastic leukemia. AB - The chromosomal abnormalities that occur in acute lymphoblastic leukemia have greatly elucidated the biologic causes (leukemogenesis) of this disease. ALL is extremely heterogeneous; different cell types at differing stages of differentiation may become leukemic. Although not yet completely understood, the chromosomal abnormalities occurring in this disease are not random. Rather, the abnormalities are highly specific, with specific abnormalities occurring in specific cell phenotypes. Early chromosomal investigations were concerned with identification of heterogeneous cytogenetic "groups," with independent prognostic indications, among patients with ALL. These studies progressed to the identification of specific chromosomal translocations, many of which can be correlated with specific cell phenotypes. Molecular studies of these cytogenetic aberrations have defined specific chromosomal breakpoints, and specific genes, which have been implicated in the oncogenic process. As a result of these translocations, the involved genes either produce abnormal products or are deregulated. The products of these genes vary, but all are concerned with cell growth and differentiation. Much remains to be determined regarding cytogenetic abnormalities in acute lymphoblastic leukemia and their clinical and biologic significance. The molecular bases of all of the recurring abnormalities in ALL have not been determined. The biologic causes for the chromosomal abnormalities are not known, nor is it known why specific chromosomal aberrations correlate with prognosis. PMID- 2228898 TI - Ontogeny of normal human B-cell and T-cell precursors and its relation to leukemogenesis. AB - The concept that a pluripotent stem cell exists and has the capacity eventually to give rise to mature B and T cells is uncontestable. However, the precise developmental relationship between pluripotent stem cells and the earliest stages of B-cell and T-cell development are still obscure. Patterns of gene expression are being identified that characterize normal B-cell and T-cell precursors, and the regulatory variables that influence self-renewal and differentiation of these cells. These are important studies because childhood lymphoblastic leukemia almost always manifests a cellular phenotype consonant with an immature lymphoid cell. A comprehensive understanding of the etiology of acute lymphoblastic leukemia will likely be hastened by a more thorough understanding of normal lymphopoiesis. This knowledge will complement the large data base that currently characterizes lymphoblastic leukemia in children. PMID- 2228899 TI - Lymphohematopoiesis: role of growth factors in leukemogenesis and therapy. AB - The interrelationship between proliferation, differentiation, and activation responses of hematopoietic progenitor cells and mature blood cells is complex. Therefore, we are only now learning what role colony-stimulating factors play in the regulation of normal hematopoiesis in vivo and in the dysregulation of hematopoiesis in leukemia. Recent advantages in molecular hematology have opened the door to the therapeutic administration of recombinant growth factors. Through continued preclinical trials in animals and by clinical trials in humans, a better understanding of the precise target cells and mechanisms of action of hematopoietic growth factors will improve the therapeutic index of administering colony-stimulating factors. Better understanding of hematopoietic growth factors will, in turn, suggest novel approaches to therapy of acute lymphoblastic leukemia. PMID- 2228900 TI - A novel assay system for quality control testing of surfaces for mammalian cell culture. PMID- 2228901 TI - Hypoxanthine increases basal and FGF-stimulated growth of porcine aortic endothelial cells in media with calf or newborn bovine serum. PMID- 2228902 TI - Growth of the malignant and nonmalignant human squamous cells in a protein-free defined medium. AB - A novel protein-free synthetic medium has been developed for the culture of human squamous cell carcinoma cells. This medium, designated PF86-1, supports the serial subcultivation of six out of nine human squamous cell carcinoma cell lines in a protein-free, chemically defined condition without the adapting culture from serum-containing conditions. These cell lines growing in PF86-1 exhibited nearly equal potency to grow in massive culture without noticeable changes in morphology but presented a significantly decreased level of colony forming efficiency when compared with the cells cultured in serum-containing media, suggesting the implication of some autocrine mechanism. Interestingly, this medium supported the growth of normal human squamous cells of oral mucosa and skin for more than 2 mo. in the primary explant culture in spite of high levels of calcium ion concentration, where the overgrowth of fibroblasts as contaminant was not observed. These results suggest that PF86-1 supports the growth of cells derived from epidermal tissues selectively and provides the same defined condition for growth of malignant and nonmalignant human squamous cells. It seems, therefore, that PF86-1 allows investigations on the products of squamous cell carcinoma cells or on the differences of growth mechanisms between normal and neoplastic human squamous cells. PMID- 2228903 TI - A serum-free system for culturing human placental trophoblasts. AB - We have compared hormone production by early gestation and term human placental trophoblasts cultured in Ham's F10 medium containing 10% fetal bovine serum with that by cells cultured in serum-free HB102 medium. Mean daily production of progesterone on Days 3 to 7 was approximately 25% less by both early gestation and term cells cultured in HB102 as compared to Ham's F10, but production was maintained at a stable level for at least 7 d longer than the cells in Ham's. Estradiol production from 10(-6) M dehydroepiandrosterone by both early gestation and term cells was comparable in both media. Human placental lactogen production on Days 3 to 7 was 40% less by cells cultured in HB102. Human chorionic gonadotropin (hCG) output by early gestation cells was also 50% less in HB102 but term cells in HB102 produced twice as much hCG as those in Ham's F10. 3B Hydroxysteroid dehydrogenase (3BHSD) activity in early gestation and term cells and 11B-hydroxysteroid dehydrogenase (11BHSD) activity of early gestation cultures was comparable in the two media. 11BHSD activity was decreased in the term cultures, and this decrease was more marked in Ham's than in HB102. Sulfatase and aromatase activities in the early gestation cultures were comparable in both media; sulfatase activity was comparable and aromatase activity only 20% less in the term cells cultured in HB102. These results indicate that serum-free HB102 supports differentiated function of human trophoblast cells and is useful for studies of placental activity for as long as 14 d in culture. PMID- 2228904 TI - Growth-promoting effects of gastrin on mouse colon cancer cells in vitro: absence of autocrine effects. AB - We have previously demonstrated trophic effects of gastrin on mouse colon cancer (MC-26) cells, in vivo, and demonstrated the presence of gastrin receptors (GR) on these cells. The cellular and intracellular mechanism by which gastrin expresses trophic effects on colon cancer cells is, however, as yet unknown. For us to start investigating the possible mechanisms involved, it was important that we first develop an in vitro model, in which gastrin expresses its trophic effects directly on the MC-26 cells. The growth-promoting effects of gastrin on the MC-26 cells were examined in various in vitro culture models, in terms of [3H]thymidine incorporation and cell number. A significant trophic effect of gastrin could be demonstrated on quiescent cells in culture, in the absence of serum. The optimal cell-culture conditions for observing trophic effects of gastrin were defined and included a 24-h period of rapid growth of MC-26 cells in serum-supplemented normal growth medium, followed by a 24-h period of culture in serum-free medium containing an optimal dose (1.0 mM) of thymidine, to achieve growth-arrest of the cells. Addition of gastrin (0.5 to 25 nM) to the quiescent, growth-arrested cells resulted in significant dose-dependent increases in both the incorporation of [3H]thymidine uptake by the cells, and a significant increase in cell number. The concentration of GR on the growth-arrested quiescent MC-26 cells in culture was significantly increased compared to the GR concentration on the control, asynchronized cells. The increased presence of GR on the growth-arrested, synchronized MC-26 cells may have allowed us to observe a significant trophic effect of gastrin on the MC-26 cells, in vitro itself. To determine if gastrin was functioning as an autocrine growth factor for MC-26 cells, we examined the effect of gastrin antibodies on the growth of MC-26 cells; no significant effect of the antigastrin IgG on the growth of MC-26 cells was observed. PMID- 2228906 TI - Ultrastructural and immunohistological characterization of the SIRC corneal cell line. AB - A widely utilized rabbit corneal cell line, SIRC, was characterized ultrastructurally and immunohistologically. Although SIRC cells are often described as being of epithelial origin, important ultrastructural and antigenic characteristics indicate that these cells are fibroblastic and not epithelial. SIRC cells lack desmosomes, cytoplasmic filaments, and cytokeratin-structures that are characteristic of corneal epithelial cells. By contrast, the dendritic morphology, presence of vimentin, and the extensive dense accumulations of ribosomes and rough endoplasmic reticulum are consistent with a fibroblastic phenotype. Collectively, the morphology, ultrastructural features, and antigenic composition favor the hypothesis that SIRC cells are fibroblastic cells (keratocytes) and not corneal epithelial cells. PMID- 2228907 TI - The detection of technical failures in perfused heart with ischemia and reperfusion by epicardial NADH fluorescence. AB - This study documents the value of continuous observation of nicotinamide adenine dinucleotide (NADH) fluorescence (NADH-F). NADH-F monitoring is used to identify ischemic regions for the recognition of minor technical failures associated with ischemia and reperfusion experiments in the isolated perfused heart system. The visualization of NADH-F is possible by simply irradiating the heart with ultraviolet light. Rat hearts, in the working-heart mode, were subjected to occlusion/reperfusion of the left coronary artery, and analyzed. The perfusate was filtered through a 5 micron pore membrane. Out of 281 hearts which were judged to be free of technical failures by conventional physiological indices (heart rate greater than 200/min, cardiac output greater than 34 ml/min, and coronary flow 9-14 ml/min), 43 (15%) disclosed an abnormal NADH-F area prior to the coronary intervention. During coronary intervention, 29 technical failures were detected as indicated by sparse NADH-F distribution with occlusion, delayed disappearance of NADH-F upon reperfusion, or the exhibition of an abnormal NADH-F region unassociated with the coronary artery supply area. These technical failures are not detectable without the use of NADH-F, although the actual number of failures detected may depend on the skill of the operator. We recommend NADH-F monitoring for any preparations which do not contain hemoglobin, since NADH-F is an intrinsic probe for ischemia and is easily applicable to a variety of experiments. PMID- 2228905 TI - Monolayer culture of rat parotid acinar cells without basement membrane substrates. AB - Acinar cells have been difficult to maintain in primary or secondary cultures over extended periods of time. The most successful monolayer culture system reported to date requires basement membrane substrates. We report here a technique for culture of rat parotid acinar cells which does not rely upon basement membrane supports for maintenance and growth. The procedure involves gland excision, treatment to chelate metal ions, enzymatic digestion with collagenases and hyaluronidase, removal of fat and red blood cells by gravimetric separation, and nylon mesh filtration to yield a homogeneous suspension of small aggregates and single cells. The cells were examined for: a) morphology, identity, and growth; b) macromolecular synthesis; and c) secretory output. They were healthy, peroxidase positive, and growing for up to 10 d. Protein synthesis increased from the point of cell layer formation at 3 to 4 d, through 10 d, while DNA synthesis decreased. As in other studies, amylase secretion fell sharply between 2 and 4 d in culture and remained low. Although previous studies indicated that the initial isolation protocol left these acinar cells unable to thrive in monolayer culture except in the presence of basement membrane substrates, the modified technique reported herein allows these cells to attach, spread, and grow on a wide variety of commercially available plasticware. This method lends itself readily to long-term analysis of rat parotid acinar cell metabolism without the complications of dedifferentiation, cell loss through culture manipulation common in suspension cultures, or complex interactions between bioactive supports and cell surfaces. PMID- 2228908 TI - Endothelin-1-induced constriction in the coronary resistance vessels and abdominal aorta of the guinea pig. AB - The purpose of this study was to examine contractile properties of endothelin-1, a newly discovered vasoactive peptide, in guinea pig coronary resistance vessels and abdominal aorta. Changes in perfusion pressure after injections of endothelin 1 were measured using a constant-flow modified Langendorff preparation. The ED10 values of coronary perfusion pressure were about 100-fold less for endothelin-1 than for prostaglandin F2 alpha. After the endothelium was damaged by exposure to free radicals, maximal coronary constriction in response to endothelin-1 (10(-9) moles) was not altered, whereas dilator responses to low doses of endothelin-1 were converted to constrictor responses. Removal of the endothelium from aortic rings significantly increased responsiveness to endothelin-1 and the maximal response to the peptide. In calcium-free medium, endothelin-1 induced small increases both in perfusion pressure in coronary vessels and in tension in the aorta. Reintroduction of calcium in the coronary and aortic preparations produced a rapid increase in perfusion pressure and tension, respectively. Further, endothelin-1-induced coronary constriction was inhibited 59% +/- 7% by nifedipine (10(-7) moles). We conclude that endothelin-1 is a more potent constrictor than prostaglandin F2 alpha in the coronary vasculature. Endothelin-1-induced constriction in the coronary vasculature of the guinea pig is not mediated through an endogenous constricting factor released from the endothelium or a constrictor prostaglandin. Further, endothelin-1-induced dilation in the coronary vasculature and attenuation of endothelin-1-induced contraction in the abdominal aorta of the guinea pig are mediated through the release of a factor from the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228909 TI - Interstitial cell infiltrate and myocardial fibrosis in dilated cardiomyopathy: a special type of cardiomegaly corresponding to sequelae of myocarditis. AB - We examined the relationship between interstitial cell infiltration and myocardial fibrosis in patients with clinically diagnosed dilated cardiomyopathy (DCM). Forty-two cases of DCM were divided into two groups, according to the mean number of the interstitial round cells per 10.2 x 10(4) square microns (Nic): the inflammatory group (Nic greater than or equal to 5) and noninflammatory group (Nic less than 5). The 12 cases in the inflammatory group were clinically similar to the 30 cases in the non-inflammatory group, but the inflammatory group exhibited a significantly (P less than 0.001) larger area of myocardial fibrosis (34.8% +/- 12.8% vs 17.5% +/- 8.2%), a significantly (P less than 0.01) higher frequency of diffuse perimyocytic-type fibrosis (83% vs 23%), fewer myocardial cells in the left ventricular wall (170 +/- 70 fibers vs 216 +/- 81 fibers), and significantly (P less than 0.01) greater hypertrophy of the myocytes (18.3 +/- 3.4 vs 15.3 +/- 2.7 microns). In addition, cases exhibiting marked fibrosis (fibrosis area greater than or equal to 25% of the myocardium) had a significantly higher Nic score (8.3 +/- 6.8) compared to cases with the less fibrotic type of DCM (4.0 +/- 5.7). We speculate that persistent or preceding inflammatory cell infiltration induces the myocardial fibrosis, especially the diffuse perimyocytic type, in the fibrosis-predominant type of DCM. Therefore, most of these cases may be a sequela of myocarditis, and more correctly termed post-myocarditic cardiomegaly. PMID- 2228910 TI - Immunological features in a case of hypereosinophilic syndrome and myocarditis. AB - The clinical and immunological follow-up of a 38-year-old female patient with hypereosinophilic syndrome and classical cardiac involvement, but without demonstrable degranulation of eosinophils and lacking binding of a specific antibody for activated eosinophils, is presented. Instead, the patient demonstrated all the immunological features of autoreactive myocarditis: cytolytic, complement-fixing antimyolemmal antibodies and increased concentrations of circulating immune complexes were present over 3 years. PMID- 2228911 TI - Chronic dissecting aneurysm of the isolated coronary artery with hemorrhagic myocardial infarction: a rare complication of cardiac operation in a female with Marfan's syndrome. AB - A 37-year-old female with Marfan's syndrome developed myocardial infarction during a cardiac operation for annuloaortic ectasia and chronic dissecting aneurysm of the aorta. At autopsy, a chronic dissecting aneurysm of the left coronary arterial system (the left main stem, anterior descending branch, first diagonal branch, and circumflex branch) showing a true lumen and a pseudo lumen, which were patent, was found. There was also a hemorrhagic myocardial infarction of the anteroseptal wall and apical portion of the left ventricle. PMID- 2228912 TI - A case of tuberculous pericarditis--use of adenosine deaminase activity (ADA) in early diagnosis. AB - Pericardial tuberculosis is rare, and because of the difficulty in isolating the causative organism, the diagnosis is often missed. Adenosine deaminase, an enzyme associated with purine metabolism, shows markedly high levels of activity in tuberculous effusion. We report a case of tuberculous pericarditis diagnosed by high levels of adenosine deaminase activity, and where the pericardial fluid cultures revealed acid-fast organisms. PMID- 2228914 TI - Bittersweet farms. AB - Bittersweet Farms, a rural Ohio farm community for autistic adults, is presented. The land and facility are described, and the importance of certain elements of location, physical plant, and layout to the program model are discussed. The Bittersweet Farms program model is presented in detail as it applies to each aspect of rural, group living, and the contribution of each of its main features to the success of the Bittersweet Farms community is discussed. PMID- 2228913 TI - The relationship between existing residential services and the needs of autistic adults. AB - Existing residential services for adults with autism vary in size, location, and source of funding. Most service options have been designed for individuals with handicaps other than autism and therefore have difficulty addressing the needs of all but the highest functioning autistic adults. This paper provides a review of the characteristics of autism that affect adaptation to residential settings. A description of existing residential options based on the combined experiences of Great Britain and North Carolina is presented, and directions for future research are then discussed. PMID- 2228915 TI - Benhaven's residential program. AB - Benhaven, a residential program of group homes providing intensive programming for autistic and neurologically impaired children, is described. Its major program factors of administration and management, treatment, support services, and family and community involvement are presented in detail. Benhaven's mission as an educational placement for preparing residents to function in the least restrictive environment on their way to future living situations is stressed. PMID- 2228916 TI - Community-based services for children and adults with autism: the Eden Family of Programs. AB - The service needs of those with autism and the response to those needs by the Eden Family of Programs are described. The Eden Family of Programs is described in detail, giving its history and discussing its participants, staff, schedules, programs, normalization, human rights, administration, and trustees. PMID- 2228917 TI - Group homes in North Carolina for children and adults with autism. AB - Autistic people not living with their families live in 11 group homes throughout North Carolina. These homes, funded by both state and federal sources, are affiliated with TEACCH, the state agency for the identification and treatment of autism. This article looks at several aspects of group homes including cost effectiveness, staff selection and training, level of structure and programming, composition of the client group, adherence to a central philosophy, and the role of administration. Evidence suggests that group homes are a viable and cost effective residential option for autistic people. While more group homes are needed, development of other residential options is encouraged. PMID- 2228918 TI - Critical issues in the residential care of people with autism. AB - There is an ever-growing need to expand both the number and range of residential services for individuals with autism while developing strategies for assuring the quality of these programs. Future program development will be facilitated by an empirical approach to the critical elements that have been identified throughout the articles in this issue. PMID- 2228919 TI - Treatment of attentional and hyperactivity problems in children with sympathomimetic drugs: a comprehensive review. AB - Issues concerning sympathomimetic drug treatment of children with attentional problems and hyperactivity are considered in light of cumulative and current research. These issues concern the atypical or "paradoxical" drug response of such children, predictability of drug response from neurological or biochemical assessments, and, especially, long-term outcome or effectiveness of sympathomimetic medication. Short-term drug effects on behavior and performance are well documented. However, follow-up studies that exist presently suggest little long-term impact of sympathomimetic drugs on school achievement, peer relationships, or behavior problems in adolescence. Questions remain concerning development of tolerance in children, ways to define subgroups of disordered children who may respond uniquely to stimulants, the efficacy of medication in combination with other treatments, and possible long-term negative consequences of medication. PMID- 2228920 TI - The DSM-III-R field trial of disruptive behavior disorders. AB - The members of the DSM-III-R Advisory Committee responsible for the diagnostic criteria for the disruptive behavior disorders (attention deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder) were able to reach agreement on potential items to be included in the final diagnostic criteria. However, there was considerable disagreement about the relative utility of different items for the three disorders and no agreement on how many items should be required from a final list of discriminating items to establish each of the diagnoses. This article describes the method and results of a national field trial of the proposed criteria. Using as a standard the diagnosis of these disorders made by expert clinicians with experience with these disorders, the diagnostic criteria that were finally included in DSM-III-R demonstrated high sensitivity, specificity, and internal consistency. PMID- 2228921 TI - Parent-based diagnosis of attention deficit disorder predicts a diagnosis based on teacher report. AB - The literature evaluating agreement between parent and teacher reports on symptoms of attention deficit disorder (ADD) has repeatedly shown only modest correlations between these two sources of information. A more relevant statistic to this clinical issue, however, is the positive predictive power, the conditional probability that diagnostic criteria will be met by teacher's report if that diagnosis has been made based on parental report. In a population of 43 children (ages 4 to 17) satisfying clinical criteria for DSM-III ADD, parents and teachers independently completed them module on ADD derived from the Diagnostic Interview for Children and Adolescents. Although correlations for individual symptoms were low to moderate, there was a 90% probability that the teacher report would result in a positive diagnosis given a positive parent diagnosis, indicating a very high probability that, in clinically referred children, a clinical diagnosis of ADD based on parent report will be corroborated by a teacher report. PMID- 2228922 TI - Clinical effects of a controlled trial of methylphenidate on adolescents with attention deficit disorder. AB - Forty-eight attention deficit disorder patients, 12 to 18 years old and without previous stimulant therapy, received a double-blind trial of methylphenidate and placebo for 3 weeks each. Stimulant treatment produced mild side effects and weight reduction. Methylphenidate significantly reduced teachers' and parents' ratings of hyperactivity, inattention, and oppositionality. In addition, patients rated themselves as clinically improved and reported elevated subjective mood during stimulant therapy. Treatment benefits were comparable for patients with and without concurrent conduct or oppositional disorder as well as those with and without past or present depressive disorders. These results support the continued effectiveness of stimulant therapy for attention deficit disorder in adolescence. However, the magnitude of clinical effectiveness reported was smaller than previously found in younger patients. PMID- 2228923 TI - Methylphenidate in aggressive-hyperactive boys: I. Effects on peer aggression in public school settings. AB - One of the least documented "known" effects of methylphenidate in hyperactive children is the suppression of peer aggression. In this study, 11 aggressive hyperactive children received a low (0.3 mg/kg) and moderate (0.6 mg/kg) dose of methylphenidate and placebo for 2 weeks each under double-blind conditions. Children were observed in public school settings during classroom seatwork activities, lunch, and recess. Results showed that methylphenidate suppressed nonphysical aggression (p = 0.06) in the classroom, and a moderate dose decreased physical aggression (p less than 0.01) and verbal aggression (p = 0.07) on the playground. The effect on the rate of appropriate social interaction was variable. The majority of subjects exhibited either the same or higher levels of appropriate social interaction on the 0.6 mg/kg dose compared with placebo. In the classroom, both doses of methylphenidate also resulted in reduced levels of motor movement, off-task behavior, noncompliance, and disruptiveness. Teacher ratings of hyperactivity and conduct problem symptoms revealed drug effects, whereas parallel parent instruments did not. PMID- 2228924 TI - Effects of methylphenidate on adolescents with aggressive conduct disorder and ADDH: a preliminary report. AB - The effect of methylphenidate on aggression in adolescents diagnosed with both aggressive conduct disorder and attention deficit disorder with hyperactivity was assessed in nine male adolescents. After three open trials, a placebo controlled double-blind design was used. During methylphenidate treatment of the six double blind subjects, there was a significant reduction of aggressivity (p's less than 0.05), as measured by the Adolescent Antisocial Behavior Checklist. Conners Teacher Rating Scale Hyperactivity and Aggression scores were in the predicted directions, but the differences were not statistically significant. PMID- 2228925 TI - The prevalence of psychotic symptoms in homeless adolescents. AB - This study was designed to gather data on psychotic symptoms in a sample of homeless adolescents. The sample included adolescents who were located in street sites as well as adolescents who were currently using shelter services. Ninety six adolescents participated in this study (mean age = 16.1 years). The results indicated that 29% of the sample reported the experience of four or more psychotic symptoms on the Diagnostic Interview Schedule psychotic symptom index. These results suggested that the endorsement of psychotic symptoms is a relatively prominent feature of the self-report of psychopathology among homeless adolescents. These symptoms did not only include reports of paranoid ideation, which may be generally elevated as part of the stress of street life, but also included reports of ideas of reference and auditory hallucinations. Moreover, these symptoms were correlated with reports of affective disturbance, abusive life experience, and a particular type of substance use. PMID- 2228926 TI - Sexualized doll play among young children: implications for the use of anatomical dolls in sexual abuse evaluations. AB - The use of anatomical dolls in sexual abuse evaluations remains controversial because of concerns that the dolls induce normal, nonabused children to act out in sexual ways that are likely to be misinterpreted as evidence of sexual abuse. This study examines the incidence of explicit sexual doll play in a large, demographically diverse sample of 2- to 5-year-olds. The 6% incidence of demonstrations of apparent sexual intercourse found in this sample compared favorably with the rate of less than 2% across prior studies of anatomical doll play among presumably nonabused children. However, higher rates of explicit sexual play were associated with being older, poor, black, and somewhat with being male, with over 20% of some subgroups of children displaying such behavior. These results are interpreted as evidence that anatomical dolls are not overly suggestive to young, sexually naive children, but are useful in assessing sexual knowledge and exposure to sexual intercourse. PMID- 2228927 TI - Specificity and sensitivity of sexually anatomically correct dolls in substantiating abuse: a pilot study. AB - Sexually anatomically correct dolls are often used to verify or refute allegations of sexual abuse in young children. As a test of their effectiveness in facilitating decisions about the abuse status of young children, the authors conducted blind interviews with six abused subjects, five nonclinic controls and four psychiatric controls. The child psychiatrist interviewer followed a standardized protocol and was able to correctly categorize 33% of the abused and 67% of the nonabused children. Proper classification was 53% for the sample using this protocol. The authors' preliminary conclusion is that, without other information available to the interviewer, sexually anatomically correct dolls are a poor source of information to decide the abuse status of a young child. The authors recommend that professionals should be cautious when basing decisions on a single instrument, such as sexually anatomically correct dolls. Mental health professionals are encouraged to maintain quality standards in evaluation of children by conducting a comprehensive examination in child sexual abuse cases. PMID- 2228928 TI - Cognitive behavioral treatment for sexually abused children suffering post traumatic stress: preliminary findings. AB - The present investigation examined the effectiveness of a cognitive behavioral treatment program designed for sexually abused children suffering post-traumatic stress disorder. Nineteen girls who suffered contact sexual abuse and met DSM-III R criteria for post-traumatic stress disorder were included in the study. Subjects ranged in age from 3 to 16 years old. Structured interviews were conducted to assess the presence or absence of post-traumatic stress disorder symptoms before, during, and following the abuse. Additionally, parents completed the Child Behavior Checklist, and subjects at least 6 years of age were administered the Child Depression Inventory and the Spielberger State-Trait Anxiety Inventory at the initial evaluation and again approximately 2 to 3 weeks later before the initiation of treatment. The baseline data collected at these two points were compared, and no significant changes were found over time. The above measures were readministered following 12 treatment sessions. The results revealed significant improvements at post-treatment on all measures. PMID- 2228929 TI - The prevalence of overanxious disorder and separation anxiety disorder: results from the Ontario Child Health Study. AB - Data from a community epidemiological study of 1,869 families (Ontario Child Health Study) was used to evaluate the effect of different ways of operationalizing DSM-III-R criteria for overanxious disorder (OAD) and separation anxiety disorder (SAD) among adolescents aged 12 to 16. The authors determined that a high threshold for symptoms to qualify as present, the presence of one or both of the essential symptoms, and the presence of four or more auxiliary symptoms for OAD and three or more for SAD gave prevalence of OAD of 3.6% and SAD of 2.4%. There was high overlap between the presence of OAD and SAD and externalizing disorder and depression, but one-half of youth with OAD and SAD had pure anxiety disorder. Youth with OAD and SAD were just as impaired as youth with externalizing disorder and depression, except that they admitted to less social isolation and their schoolwork was less affected. PMID- 2228930 TI - Symptoms of anxiety disorders in normal children. AB - The present study examined prevalence, expression, and developmental patterns of DSM-III-R anxiety disorder symptoms in 62 never-psychiatrically-ill children. Subclinical phobias and overanxious disorder symptoms were fairly common, while symptoms of other anxiety disorders were less common. Direction of sex and age differences was generally consistent with previous literature, but few reached statistical significance. Nonanxious and subclinically anxious subsamples of never-psychiatrically-ill subjects were compared on individual and family psychopathology. Subclinically anxious children showed greater individual and family psychopathology than nonanxious children, though differences decreased at 12-month follow-up. Anxiety as a normal developmental phenomenon is discussed. PMID- 2228931 TI - Obsessive compulsive disorder in children and adolescents: phenomenology and family history. AB - Phenomenology and family history in 21 clinically referred children and adolescents with obsessive compulsive disorder are described. Each child and family participated in a standard clinical psychiatric assessment. The most frequently reported symptoms were repeating rituals, washing, ordering and arranging, checking, and contamination concerns. Controlling behaviors involving other family members were seen in 57% of the patients. Associated psychopathology was common: 38% received an anxiety disorder diagnosis; 29% received a mood disorder diagnosis; tics were observed in 24%. Fifteen (71%) of the children had a parent with either obsessive compulsive disorder (N = 4) or obsessive compulsive symptoms (N = 11). The clinical and research implications of these findings are discussed. PMID- 2228932 TI - Comparative studies of pharmacotherapy for school refusal. AB - Two studies compared alprazolam and imipramine in the treatment of school refusal. In an open label study (N = 17), two-thirds of the subjects completing a trial in both the alprazolam and imipramine groups showed moderate to marked global improvement in symptoms of anxiety and depression. In the double-blind, placebo-controlled study (N = 24), posttreatment scores calculated as change from baseline on the Anxiety Rating for Children were significantly different (p = .03) among the three treatment groups, with the active medication groups showing the most improvement. Additionally, on all depression rating scales, similar trends were evident with the alprazolam and imipramine groups demonstrating greater improvement than the placebo group. However, analyses of covariance (with pretreatment scores as the covariates) showed no significant differences among the three treatment groups on change in anxiety and depression scales. Thus, additional research is needed to determine whether trends in this study are explained by drug effect or baseline differences on rating scales. PMID- 2228933 TI - Diagnosis of panic disorder in prepubertal children. AB - Few reports on panic disorder in children are available, despite the retrospectively documented onset in childhood of about 20% of the cases of adult panic disorder. The authors report on six prepubertal children, aged 8 to 13 years, who met DSM-III-R criteria for adult-type panic disorder. Hyperthyroidism, cardiologic, and respiratory problems were excluded as well as abuse of caffeine or other drugs. The first panic attack occurred between 5 to 11 years of age, with an average interval of 3 years between onset of the disorder and diagnosis. Mitral valve prolapse was documented in two cases. Family history was always positive for panic disorder. Although not common, panic disorder should be considered in children with school phobia and positive family history. As it is in adults, mitral valve prolapse may be associated with panic disorder in children. PMID- 2228934 TI - Panic disorder on a child psychiatric consultation service. AB - In a review of all cases seen from 1984 to 1988 by the psychiatric consultation liaison service of a tertiary referral pediatric hospital, four cases of definite panic disorder meeting DSM-III-R criteria were identified. Three of these children were referred to the consultation service after intensive investigation of physical complaints had failed to yield a diagnosis. These cases of panic disorder differed from those previously reported in child psychiatric populations by their relative absence of psychiatric comorbidity. This suggests that uncomplicated panic disorder may present with primarily somatic symptoms in pediatric subspecialty clinics, while panic disorder, complicated by behavioral or emotional disturbance, is more likely to present directly to child psychiatric services. Children presenting with somatic symptoms are at risk for receiving nonproductive investigations while having delayed diagnosis and treatment of the panic disorder. PMID- 2228935 TI - Applying impairment criteria to children's psychiatric diagnosis. AB - This paper examines the effect of applying impairment criteria using the Children's Global Assessment Scale on rates, agreement between informants, and recall of diagnosis over 2 years in a sample of 220 offspring of depressed and nondepressed parents. The findings show that the offspring of depressed parents, compared with nondepressed parents, were more impaired overall. The rates of most psychiatric disorders in both groups of children were markedly reduced when impairment criteria were applied. The application of impairment criteria improved agreement between mother and child on many of the children's diagnoses and also improved stability of recall of child's diagnosis at 2-year follow-up. Long-term follow-up studies are needed to determine the clinical consequences for children who meet diagnostic criteria for psychiatric disorder but who have minimal functional impairment. PMID- 2228936 TI - Impairment in the epidemiological measurement of childhood psychopathology in the community. AB - The desirability of incorporating a measure of impairment to the categorization of childhood psychopathology in the community is examined. The use of the Children's Global Assessment Scale (CGAS) for this purpose is recommended. The choice of 61 (definite case) and 71 (probable case) as cutpoints on the Children's Global Assessment Scale is supported empirically by the data on service utilization, parental perceived need, and behavior problem scores obtained in the Puerto Rico Child Psychiatry Epidemiological Study. PMID- 2228937 TI - Children at risk: II. Risk factors and clinic utilization. AB - Using a strategy involving multiple raters and instruments, the authors compared 134 clinic subjects with controls matched on sex, age, and socioeconomic status to determine how various risk factors are related to clinic utilization apart from their effects on children's symptomatology. Parental psychopathology, family size, and marital status were most predictive of children's symptom levels, while stress levels, family size, and marital status were most predictive of clinic utilization. Although children's total symptom levels explained 27.6% of the variance in clinic utilization, other factors (family size, family history of divorce, stress, and parental psychopathology) explained an additional 13.2% of the variance. Findings indicate that clinicians and health care planners must carefully assess variables other than children's symptom levels in order to better understand children's mental health services utilization, develop more robust models of risk, and increase the effectiveness of our efforts directed towards prevention and intervention. PMID- 2228938 TI - Alcoholism and substance abuse teaching in child psychiatry residency programs. AB - In order to determine the needs and goals of substance abuse teaching, vis-a-vis child psychiatry training, a questionnaire was sent to the training directors at every child psychiatry program accredited by the Accreditation Council of Graduate Medical Examination. The results demonstrated that most child psychiatry programs schedule at least some didactic time specifically for substance abuse topics. However, only 59% of the training directors felt that their fellows were adequately educated to identify and at least initially manage a drug abusing adolescent. PMID- 2228939 TI - A model curriculum for substance abuse education in child and adolescent psychiatry training programs. AB - Child psychiatry training recognizes substance abuse as a problem requiring an educational effort to provide fellows with adequate clinical skills to manage these patients. The components of a substance abuse educational module which may be integrated into existing child psychiatry fellowships are presented, with a discussion of practical problems raised by the expansion of child psychiatry into this neglected area. PMID- 2228940 TI - A study of the Board Certification Examination in Child and Adolescent Psychiatry. AB - In 1977, training directors of 55 child psychiatry training programs agreed to provide the Committee on Certification in Child Psychiatry of the American Board of Psychiatry and Neurology, Inc. with confidential data about the clinical performance of each of their graduates in 1978, 1979, and 1980. Information about 267 graduates from 37 programs was received. Almost all programs were university affiliated and located in medical centers. By 1986, 112 of these graduates had taken the child aboard examination. Training director ratings were found to be statistically correlated to a significant degree with actual pass or fail results on the written and on the overall examination. PMID- 2228941 TI - Resolved: children should be told of their adoption before they ask. PMID- 2228942 TI - Does panic disorder exist in childhood? PMID- 2228943 TI - From DSM-III-R to DSM-IV. PMID- 2228944 TI - Subtypes of conduct disorder. PMID- 2228945 TI - Psychological screening for the pediatrician. PMID- 2228946 TI - Pharmacotherapy of aggression. PMID- 2228947 TI - Antistuttering medication? PMID- 2228948 TI - More on ECT. PMID- 2228949 TI - Ultrasonographic findings in peptic ulcer: a report on 24 cases proven endoscopically. AB - A series of 24 patients is presented who had routine upper abdominal sonography for reason of atypical abdominal pain; in all cases the sonographically suggested diagnosis of a mucosal ulceration was proved by a following endoscopy. The ultrasonic findings were localized thickening of the gastric wall in combination with presence of liquid intragastrically in a fasting patient. PMID- 2228950 TI - [Left adrenal gland hemorrhage as isolated lesions following blunt trauma]. AB - Posttraumatic hemorrhage of the adrenals usually occurs in the right or in both glands. This report describes one case of isolated, posttraumatic hemorrhage of the left adrenal in a 56-year-old woman. US examination shows a mass, almost isoreflective with the spleen, with central bright echoes, which are characteristic of fresh hematoma. CT examination displays a dense, relatively well-defined mass lesion causing a spread of the adrenal limbs. Density measurements are typical for hematoma. Follow-up examination one week later demonstrates partial regression of the lesion in volume and density. PMID- 2228951 TI - [Diagnosis and percutaneous treatment of pulmonary hydatid cyst. State of the problem apropos of a case]. AB - A pulmonary hydatid cyst was diagnosed and cured by percutaneous CT guided aspiration. Pleural effusion related to incomplete aspiration of the loculated cyst was observed. No deleterious effect occurred, after a follow-up of 22 months. PMID- 2228952 TI - [Prenatal bowing of the long bones]. AB - A case of congenital angulation and bowing of the long bones is reported. The condition belongs to a group of bone pathologies which have as a common feature an abnormal bowing of the diaphysis. The cortex at the concave side shows a thickening while the convex side shows a cortical thinning, corresponding to a structural adaptation to external compressing forces at the site of the bowing of the bone. The angulation is a consequence of bowing of long bones over other foetal parts. PMID- 2228953 TI - The role of CT in the diagnosis of adenocarcinoma of the ethmoid. AB - A retrospective study of 26 patients with ethmoid adenocarcinoma is presented. CT proves to be of great diagnostic value in demonstrating the location and extension of these tumors. The only interpretation problem that may exist is the overestimation of the tumor extension due to the occurrence of retro-obstructive sinusitis. PMID- 2228954 TI - MRI of intraparenchymal hematoma: responsible mechanisms. AB - The MRI appearance and evolution of hemorrhage remains a difficult entity. A typical example of the MR visualization of an intracerebral bleeding in the basal ganglia and the internal capsule at 1.5 T is presented. The sequential biochemical and physical changes in an hemorrhage are described. PMID- 2228955 TI - Agrobacterium rhizogenes mutants that fail to bind to plant cells. AB - Transposon insertion mutants of Agrobacterium rhizogenes were screened to obtain mutant bacteria that failed to bind to carrot suspension culture cells. A light microscope binding assay was used. The bacterial isolates that were reduced in binding to carrot cells were all avirulent on Bryophyllum diagremontiana leaves and on carrot root disks. The mutants did not appear to be altered in cellulose production. The composition of the medium affected the ability of the parent and mutant bacteria to bind to carrot cells. The parent strain bound to carrot cells in greatest numbers in low-ionic-strength media such as 4% sucrose but still showed significant binding in Murashige-Skoog tissue culture medium. All of the mutants showed reduced binding in 4% sucrose after 2 h of incubation with carrot cells. One mutant was delayed in binding in 4% sucrose. This mutant and one other mutant also showed reduced binding to carrot cells in Murashige-Skoog medium. To determine whether the Tn5 insertion was responsible for the mutant phenotype, DNA containing the Tn5 insertion was cloned from the mutant bacteria and used to introduce Tn5 into the parent strain in the same location as in the original mutant by marker exchange. The resulting transconjugants had the same avirulent, nonattaching phenotype as the original mutants, suggesting that the mutant phenotype was due to the Tn5 insertion. The cloned DNA containing the Tn5 insertion was also tested for homology to DNA of known genes that affect attachment of Agrobacterium tumefaciens to plant cells by DNA hybridization. No homology to chv, att, or pscA clones was observed. In addition, cloned chv, att, and pscA genes from A. tumefaciens were unable to complement the attachment-minus A. rhizogenes mutants. Thus, the A. rhizogenes nonattaching mutants appear to be different from the previously described A. tumefaciens mutants. PMID- 2228956 TI - The level of a transcript required for production of a Streptomyces coelicolor antibiotic is conditionally dependent on a tRNA gene. AB - In Streptomyces coelicolor A3(2), bldA mutants are conditionally defective in aerial mycelium formation and fail to synthesize all four antibiotics produced by bldA+ strains. Previous studies showed that bldA specifies the tRNA for the rarely used leucine codon UUA. Here we describe experiments examining the abundance in a bldA mutant of a transcript involved in antibiotic production. With use of a bacteriophage-based integrative vector, a promotorless xylE reporter gene was inserted into a previously undescribed gene for an early step in biosynthesis of the red antibiotic undecylprodigiosin, located in the red gene cluster. With this transcriptional fusion present at unit copy number in the chromosome, xylE expression in a bldA+ strain was maximal late in growth in a liquid production medium and was virtually absent in a bldA mutant. On plates of a different medium, the bldA mutant was able to produce undecylprodigiosin and to express the red::xylE fusion, but both abilities were repressed by increasing the concentration of phosphate in the medium. These experiments showed that the undecylprodigiosin deficiency of bldA mutants cannot be accounted for by the presence of TTA codons in the red structural genes, but rather that bldA influences red gene mRNA abundance. In low-phosphate conditions, an alternative regulatory pathway can lead to red gene expression. PMID- 2228957 TI - LexA-independent expression of a mutant mucAB operon. AB - pKM101 is a naturally occurring plasmid that carries mucAB, an analog of the umuDC operon, the gene products of which are required for the SOS-dependent processing of damaged DNA necessary for most mutagenesis. Genetic studies have indicated that mucAB expression is controlled by the SOS regulatory circuit, with LexA acting as a direct repressor. pGW16 is a pKM101 derivative obtained by N methyl-N'-nitro-N-nitrosoguanidine mutagenesis that was originally identified on the basis of its ability to cause a modest increase in spontaneous mutation rate. In this report, we show that pGW16 differs from pKM101 in being able to enhance methyl methanesulfonate mutagenesis and to confer substantial resistance to UV killing in a lexA3 host. The mutation carried by pGW16 is dominant and was localized to a 2.4-kb region of pGW16 that includes the mucAB coding region and approximately 0.6 kb of the 5'-flanking region. We determined the sequence of a 119-bp fragment containing the region upstream of mucAB and identified a single base-pair change in that region, a G.C-to-A.T transition that alters a sequence homologous to known LexA-binding sites. DNA gel shift experiments indicate that LexA protein binds poorly to a 125-bp fragment containing this mutation, whereas a fragment containing the wild-type sequence is efficiently bound by LexA. This mutation also alters an overlapping sequence that is homologous to the -10 region of Escherichia coli promoters, moving it closer to the consensus sequence. The observation that the synthesis of pGW16-encoded mucAB proteins in maxicells is increased relative to that of pKM101-encoded mucAB proteins even in the absence of a lexA+ plasmid suggests that this mutation also increases the activity of the mucAB promoter. PMID- 2228958 TI - Analysis of the Erwinia chrysanthemi arb genes, which mediate metabolism of aromatic beta-glucosides. AB - Erwinia chrysanthemi is one of the few members of the family Enterobacteriaceae that is capable of metabolizing most of the naturally occurring beta-glucosides. We previously isolated the clb genes, which allow the use of the disaccharide cellobiose as well as the aromatic beta-glucosides arbutin and salicin. We report here the isolation of the arb genes, which permit fermentation of the aromatic beta-glucosides only. Establishment of a functional Arb system in Escherichia coli depended on the presence of the phosphotransferase system and on the activation by the cyclic AMP-cyclic AMP receptor protein complex. Strains carrying mini-Mu-induced LacZ fusions to the arb genes were used to analyze arb genes organization and function. Three arb genes (arbG, arbF, and arbB) were identified and organized in this order. Genetic and structural evidence allowed us to assign a phospho-beta-glucosidase and a permease activity to the ArbB and ArbF proteins, respectively. Several Lac+ arb-lacZ insertions were introduced into the E. chrysanthemi chromosome. Both ArbG- and ArbF- strains were unable to ferment the aromatic beta-glucosides, whereas ArbB- strains were impaired only in salicin fermentation. None of the mutations in the arb genes affected cellobiose metabolism. The expression of the arb genes was substrate inducible and required the ArbF permease and, possibly, the ArbG protein. Collectively, our results underline the resemblance between the naturally expressed E. chrysanthemi arbGFB and the cryptic E. coli bglGFB operons, yet the arbG gene product seemed unable to activate E. coli bgl operon expression. PMID- 2228959 TI - The Escherichia coli polB gene, which encodes DNA polymerase II, is regulated by the SOS system. AB - The dinA (damage inducible) gene was previously identified as one of the SOS genes with no known function; it was mapped near the leuB gene, where the polB gene encoding DNA polymerase II was also mapped. We cloned the chromosomal fragment carrying the dinA region from the ordered Escherichia coli genomic library and mapped the dinA promoter precisely on the physical map of the chromosome. The cells that harbored multicopy plasmids with the dinA region expressed very high levels of DNA polymerase activity, which was sensitive to N ethylmaleimide, an inhibitor of DNA polymerase II. Expression of the polymerase activity encoded by the dinA locus was regulated by SOS system, and the dinA promoter was the promoter of the gene encoding the DNA polymerase. From these data we conclude that the polB gene is identical to the dinA gene and is regulated by the SOS system. The product of the polB (dinA) gene was identified as an 80-kDa protein by the maxicell method. PMID- 2228961 TI - Cross talk to the phosphate regulon of Escherichia coli by PhoM protein: PhoM is a histidine protein kinase and catalyzes phosphorylation of PhoB and PhoM-open reading frame 2. AB - Transcription of the genes in the phosphate regulon in Escherichia coli is activated by PhoB protein, which is phosphorylated by PhoR protein under phosphate-limiting conditions. In the absence of the phoR function, the genes in the phosphate regulon are expressed constitutively and the expression is dependent on the function of phoM and phoB. We constructed a plasmid with a lacZ' 'phoM fusion gene, which encoded a hybrid protein (PhoM1206) in which the hydrophobic amino-terminal half of the native PhoM was replaced by beta galactosidase. The phoM1206 gene could complement the phoM mutation in vivo. We purified PhoM1206 from the overproducing strain carrying the plasmid; it was autophosphorylated at a histidine residue in the presence of ATP, and the phospho PhoM1206 phosphorylated PhoB. PhoM1206 could also transphosphorylate the product of phoM-orf2, which is structurally homologous to phoB and located immediately upstream of phoM. Although PhoR1084 that lacked the hydrophobic amino-terminal region of the native PhoR protein transphosphorylated PhoB, it could not phosphorylate PhoM-open reading frame 2. Therefore, cross talk by protein phosphorylation appears to occur from PhoM to PhoB but not from PhoR to PhoM-open reading frame 2. PMID- 2228960 TI - Purification and preliminary characterization of the Escherichia coli K-12 recF protein. AB - The recF gene of Escherichia coli is known to encode an Mr-40,000 protein that is involved in DNA recombinationa nd postreplication DNA repair. To characterize the role of the recF gene product in these processes, the recF gene was cloned downstream of a tac promoter to facilitate overproduction of the recF gene product. The RecF protein was overproduced and purified to apparent homogeneity. N-terminal protein sequence analysis demonstrated that the purified protein had the sequence that was predicted from the DNA sequence of the recF gene, except that the predicted N-terminal Met was not present. The RecF protein bound to single-stranded oligonucleotides in filter binding and gel filtration assays. Maximal binding required 2 to 3 min of incubation at 37 degrees C; the binding reaction had a pH optimum of 7.0, did not require divalent cations, and was inhibited by NaCl concentrations of greater than 250 mM. The Kd of RecF protein binding to a 59-base single-stranded oligonucleotide was on the order of 1.3 X 10(-7) M, and the reaction did not show cooperativity. Experiments measuring the binding to various DNA substrates and competition binding experiments with different DNA molecules demonstrated that RecF protein binds preferentially to single-stranded, linear DNA molecules. PMID- 2228962 TI - Cloning, mapping, and sequencing of the gene encoding Escherichia coli quinoprotein glucose dehydrogenase. AB - Escherichia coli contains pyrroloquinoline quinone-dependent glucose dehydrogenase. We cloned and sequenced the gene (gcd) encoding this enzyme and showed that the derived amino acid sequence is highly homologous to that of the gdhA gene product of Acinetobacter calcoaceticus. Stretches of homology also exist between the amino acid sequence of E. coli glucose dehydrogenase and other pyrroloquinoline quinone-dependent dehydrogenases from several bacterial species. The position of gcd on the chromosomal map of E. coli was determined to be at 3.1 min. PMID- 2228963 TI - Bacteriophage T4 nrdA and nrdB genes, encoding ribonucleotide reductase, are expressed both separately and coordinately: characterization of the nrdB promoter. AB - We examined the expression of the bacteriophage T4 nrdA and nrdB genes, which encode the alpha 2 and beta 2 subunits, respectively, of ribonucleoside diphosphate reductase, the first committed enzyme in the pathway of synthesis of the deoxyribonucleoside triphosphates. T4 nrdA, located 700 bp upstream from nrdB, has been shown previously to be transcribed by two major transcripts: a prereplicative, polycistronic message, TU, orginating at an immediate-early promoter, PE, that is 3.5 kb upstream from nrdA, and a postreplicative message commencing from a late promoter in its 5' flank. We have found a third promoter initiating a transcript at 159 nucleotides upstream from the reading frame of nrdB. PnrdB functions only in the presence of the T4 motA gene product, which is required for middle (time) promoters, and therefore the onset of nrdB transcription is delayed more than 2 min after infection. Because of the distance of nrdA from PE, the inception of nrdA transcription (delayed early) coincides closely with that of nrdB. An apparent termination site, tA, occurs about 80 bp downstream from nrdA. Some of the polycistronic mRNA reading through the site after 5 min contributes to nrdB transcription. nrdA and nrdB genes in an uninfected host have been reported to be transcribed only coordinately. In contrast, T4 nrdA and nrdB are initially transcribed separately onto the PE and PnrdB transcripts, respectively, but at about 5 min after infection are transcribed both coordinately and on separate transcripts. Evidence is presented that TU coordinately transcribes a deoxyribonucleotide operon in the order: frd, td, gene 'Y,' nrdA, nrdB. Since the beta 2 subunit is known to be formed after the alpha 2 subunit, the expression of the nrdB gene determines the onset of deoxyribonucleoside triphosphate synthesis and thus of T4 DNA replication. PMID- 2228964 TI - Cloning, expression, and nucleotide sequence of the Lactobacillus helveticus 481 gene encoding the bacteriocin helveticin J. AB - Lactobacillus helveticus 481 produces a 37-kDa bacteriocin called helveticin J. Libraries of chromosomal DNA from L. helveticus were prepared in lambda gt11 and probed for phage-producing fusion proteins that could react with polyclonal helveticin J antibody. Two recombinant phage, HJ1 and HJ4, containing homologous inserts of 350 and 600 bp, respectively, produced proteins that reacted with antibody. These two phage clones specifically hybridized to L. helveticus 481 total genomic DNA but not to DNA from strains that did not produce helveticin J or strains producing unrelated bacteriocins. HJ1 and HJ4 lysogens produced beta galactosidase fusion proteins that shared similar epitopes with each other and helveticin J. The intact helveticin J gene (hlv) was isolated by screening a library of L. helveticus chromosomal DNA in lambda EMBL3 with the insert DNA from phage HJ4 as a probe. The DNA sequence of a contiguous 3,364-bp region was determined. Two complete open reading frames (ORF), designated ORF2 and ORF3, were identified within the sequenced fragment. The 3' end of another open reading frame, ORF1, was located upstream of ORF2. A noncoding region and a putative promoter were located between ORF1 and ORF2. ORF2 could encode an 11,808-Da protein. The L. helveticus DNA inserts of the HJ1 and HJ4 clones reside within ORF3, which begins 30 bp downstream from the termination codon of ORF2. ORF3 could encode a 37,511-Da protein. Downstream from ORF3, the 5' end of another ORF (ORF4) was found. A Bg/II fragment containing ORF2 and ORF3 was cloned into pGK12, and the recombinant plasmid, pTRK135, was transformed into Lactobacillus acidophilus via electroporation. Transformants carrying pTRK135 produced a bacteriocin that was heat labile and exhibited an acitivity spectrum that was the same as that of helveticin J. PMID- 2228965 TI - Transcription of the Shiga-like toxin type II and Shiga-like toxin type II variant operons of Escherichia coli. AB - Shiga-like toxin type II (SLT-II) and Shiga-like toxin type II variant (SLT-IIv) are cytotoxins produced by certain strains of Escherichia coli. Nucleotide sequence analyses had revealed that the structural genes for the A subunit and B subunit of SLT-II or SLT-IIv are arranged in an operon. Primer extension and S1 nuclease protection analyses identified a promoter for the slt-II operon 118 bases upstream of the slt-IIA gene. The slt-IIv promoter was demonstrated to be identical to the slt-II promoter. The slt-II and slt-IIv promoters differed significantly from the previously characterized Shiga toxin (stx) and Shiga-like toxin type 1 (slt-I) promoters. The transcriptional efficiencies of the stx and slt-II promoters were compared in fusions to the chloramphenicol acetyltransferase gene, and constitutive expression of the slt-II promoter was found to be equivalent to derepressed expression of the stx promoter. In contrast to the stx and slt-I promoters, the slt-II and slt-IIv promoters did not contain sequences for binding of the Fur repressor protein, and SLT-II production was not determined by iron levels in the media in various E. coli strains with wild-type or mutant ferric uptake regulation (fur) alleles. Northern (RNA) blot analysis demonstrated a single mRNA transcript for the slt-II operon, and further analysis of the slt-II operon by primer extension did not reveal an independent promoter for the B subunit gene. A putative rho-independent transcription terminator was identified 274 bases downstream of slt-IIB. These data indicated that the slt-II and slt-IIv operons differ from the stx/slt-I operon in regulation of their transcription by iron. Whether these regulatory differences enable the type I and type II groups of Shiga-like toxins to perform different roles in the pathogenesis of infectious diseases remains to be established. PMID- 2228966 TI - Beta-lactamase expression in Streptomyces cacaoi. AB - Plasmids were prepared by inserting genomic DNA fragments from Streptomyces cacaoi within the mel gene of plasmid pIJ702. The inserted DNA fragments contain the beta-lactamase-encoding bla gene and upstream nucleotide sequences of various lengths. The transcription start point of bla was identified by nuclease S1 mapping. Upstream nucleotide sequences of sufficient lengths had an enhancing effect on beta-lactamase production by the Streptomyces host. The dot blot hybridization assay revealed that this effect was exerted at the transcriptional level. Experimental evidence strongly suggests that the underlying mechanism involves, at least in part, one or several trans-acting elements. In one of the constructs, in which the upstream nucleotide sequence was reduced to 0.3 kb, the bla promoter was present but the bla gene was expressed by readthrough from a promoter, possibly the mel promoter, of the pIJ702 vector. PMID- 2228967 TI - Purification and characterization of the reduced-nicotinamide-dependent 2,2' dithiodiethanesulfonate reductase from Methanobacterium thermoautotrophicum delta H. AB - A novel reduced nicotinamide-dependent disulfide reductase, the 2,2' dithiodiethanesulfonate [(S-CoM)2] reductase (CoMDSR) of Methanobacterium thermoautotrophicum was purified 405-fold to electrophoretic homogeneity. Both NADPH and NADH functioned as electron donors, although rates with NADPH were three times higher. Reduced factor F420, the deazaflavin electron carrier characteristic of methanogenic bacteria, was not a substrate for the enzyme. The enzyme was most active with (S-CoM)2 but could also reduce L-cystine at 23% the (S-CoM)2 rate. Results of sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that the enzyme was monomeric with an Mr of about 64,000; spectral analysis showed that it was a flavoprotein with an estimated composition of one molecule of flavin per polypeptide. Maximal activity occurred at 64 degrees C, and the pH optimum was 8.5. The apparent Km for both NADPH and (S-CoM)2 was 80 microM. The enzyme was completely inactivated by oxygen in crude cell extracts but was oxygen stable in the homogeneous state. The low activity of the CoMDSR in cell extracts as well as its relatively low rate of reducing CoM-S S-HTP (the heterodisulfide of the two thiol cofactors involved in the last step of methanogenesis) make it unlikely that it plays a role in the methylreductase system. It may be involved in the redox balance of the cell, such as the NADPH dependent bis-gamma-glutamylcystine reductase with which it shows physical similarity in another archaebacterium, Halobacterium halobium (A. R. Sundquist and R. C. Fahey, J. Bacteriol. 170:3459-3467, 1988). The CoMDSR might also be involved in regenerating the coenzyme M trapped as its homodisulfide, a nonutilizable form of the cofactor. PMID- 2228968 TI - Control of diauxic growth of Azotobacter vinelandii on acetate and glucose. AB - Batch cultures of Azotobacter vinelandii were inoculated with cells pregrown on either acetate or glucose. When they were subsequently grown on a mixture of acetate and glucose, typical diauxic growth was observed, with preferential uptake of acetate in the first and glucose in the second phase of growth. Extracts from acetate-pregrown cells exhibited high acetate kinase activity in the first phase of growth. This activity decreased and activities of the two glucose enzymes glucose 6-phosphate dehydrogenase and glyceraldehyde 3-phosphate dehydrogenase increased in the second phase. Extracts from glucose-pregrown cells exhibited high initial activities of the two glucose enzymes, which decreased while acetate kinase activity increased in the first phase of growth. Again, in the second phase, activities of the two glucose enzymes increased and acetate kinase activity decreased. In any case, isocitrate dehydrogenase activity varied only slightly and unspecifically. The differences in enzyme activity and the constancy of isocitrate dehydrogenase were confirmed by experiments with either acetate- or glucose-limited chemostats. In chemostats in which both of the substrates were limiting, all of the enzymes displayed significant activities. Glucose 6-phosphate dehydrogenase activity was inhibited by acetyl coenzyme A and acetyl phosphate but not by acetate. It is proposed that diauxic growth is based on the control of enzymes involved in acetate or glucose dissimilation by which acetate or its metabolites control the expression and activity of glucose enzymes. PMID- 2228969 TI - Interaction of RecA protein with acidic phospholipids inhibits DNA-binding activity of RecA. AB - The RecA protein of Escherichia coli binds specifically to acidic phospholipids such as cardiolipin and phosphatidylglycerol. This binding appears to be affected by the presence of divalent cations such as Ca2+ and Mg2+. The interaction leads to the inhibition of RecA binding to at least two different conformations of DNA, single-stranded DNA and left-handed Z-DNA, thus suggesting that the phospholipids interact at the DNA-binding site of the RecA protein. Inclusion of a nucleotide cofactor [adenosine 5'-O-(gamma-thiotriphosphate)] in the reactions did not prevent the inhibition of DNA-binding activities of RecA protein by the phospholipids. The interaction of RecA protein with cardiolipin and phosphatidylglycerol, which represent two of the three major phospholipids of the E. coli membrane, may be physiologically important, as it provides a possible mechanism for the RecA-membrane association during the SOS response. These observations raise the possibility that the Z-DNA-binding activity of RecA protein is merely a manifestation of its phospholipid-binding property. PMID- 2228970 TI - Enterohemolysin production is associated with a temperate bacteriophage in Escherichia coli serogroup O26 strains. AB - A temperate bacteriophage that determines the expression of enterohemolysin was isolated from Escherichia coli O26 strain C3888. The genetic determinant associated with enterohemolysin production (E-Hly determinant) was cloned from EcoRI-digested bacteriophage DNA in vector plasmid pUC8. pUC8 recombinant plasmid pEO19 carries a 3.7-kb EcoRI insert of phage DNA, and enterohemolysin was expressed in E. coli K-12 after transformation. Hemolysin-negative derivatives of pEO19 were generated by transposon mutagenesis with Tn1725. By subcloning, the phage E-Hly determinant was assigned to a 2,150-bp piece of DNA which is flanked by EcoRI and AccI restriction sites. The enterohemolysin-producing recombinant strains and wild-type strain C3888 express a 60-kDa protein which was detected in the bacterial outer membrane by Western immunoblotting. Biologically active enterohemolysin was detected only in bacteria grown to the stationary phase, and the hemolysin was not released into the culture medium. Lysis of erythrocytes was inhibited by 30 mM dextran 4, which functions as an osmotic protectant without destroying the enterohemolysin itself. PMID- 2228971 TI - Characterization of sodium dodecyl sulfate-stable Staphylococcus aureus bacteriolytic enzymes by polyacrylamide gel electrophoresis. AB - Profiles of the bacteriolytic activities of Staphylococcus aureus culture supernatants, sodium dodecyl sulfate cell extracts, LiCl cell extracts, cell wall extracts, and cell membranes were analyzed in sodium dodecyl sulfate polyacrylamide gels containing Micrococcus luteus or S. aureus. A total of 20 distinct bands of bacteriolytic activity could be detected in gels containing M. luteus, 8 of these bands were found in culture supernatants. The sodium dodecyl sulfate cell extracts, the LiCl cell extracts, and the cell membranes each contained 20 bands (P1 to P20), but no activity was found in cell wall extracts. Less bacteriolytic activity could be detected in gels containing S. aureus, although three bands were found in culture supernatants and LiCl extracts and cell membranes contained one major band, P13. Crude cell extracts showed five bacteriolytic bands of which the major bacteriolytic bands were distributed in an identical manner in all 10 strains of S. aureus studied. The effects of chemical and physical factors were determined, and it was shown that iodoacetic acid, Hg2+, and Cibacron Blue 3G-A reduced activity, and an optimum pH for enzyme detection was between 7 and 8. Preincubation at 100 degrees C for 30 min reduced the activity of P1 and P2 bands. PMID- 2228972 TI - Unusual septum formation in Streptococcus pneumoniae mutants with an alteration in the D,D-carboxypeptidase penicillin-binding protein 3. AB - An internal 630-bp DNA fragment of the gene encoding penicillin-binding protein 3 (PBP 3) (dacA) of Streptococcus pneumoniae was identified in a lambda gt11 gene bank screened with anti-PBP 3 antiserum. The deduced 210-amino-acid sequence showed a high degree of homology to the low-molecular-weight PBPs 5 and 6 of Escherichia coli and Bacillus subtilis PBP 5. Viable mutants lacking a C-terminal part of PBP 3 were obtained after a plasmid containing the dacA fragment was integrated into the PBP 3 gene by homologous recombination. The truncated PBP 3* was still active in terms of beta-lactam binding. Most PBP 3 was found in the growth medium, indicating that membrane anchoring of PBP 3 is provided by the C terminus, as has been shown for other D,D-carboxypeptidases. The mutant cells grew with a slower generation time than the wild type in the shape of irregular enlarged spheres. In addition, as revealed by electron microscopy, cell separation was severely affected, septa were found unevenly distributed at multiple sites within the cells, and the murein layer appeared variable in thickness. PMID- 2228973 TI - Molecular cloning and nucleotide sequence of the beta-lytic protease gene from Achromobacter lyticus. AB - Two bacteriolytic enzymes secreted by Achromobacter lyticus M497-1 were purified and identified as being very similar (considering their amino acid composition and N-terminal sequence) to alpha- and beta-lytic proteases from Lysobacter enzymogenes. A 1.8-kb EcoRI fragment containing the structural gene for beta lytic protease was cloned from A. lyticus chromosomal DNA. The protein sequence deduced from the nucleotide sequence was identical to the known sequence of beta lytic protease, except for six residues. The nucleotide sequence revealed that the mature enzyme is composed of 179 amino acid residues with an additional 195 amino acids at the amino-terminal end of the enzyme, which includes the signal peptide, thus indicating that the enzyme is synthesized as a precursor protein. PMID- 2228974 TI - Biosynthesis of a membrane adhesion zone fraction throughout the cell cycle of Escherichia coli. AB - Synchronized cells of Escherichia coli were pulse-labeled with [3H]leucine and subjected to membrane fractionation to determine whether a fraction that is enriched for membrane-murein adhesion zones (fraction OML) was preferentially generated at specific times during the cell cycle, as previously suggested from studies of lkyD and cha mutants. Contrary to this prediction, the experiments showed that OML was formed continuously during the division cycle. PMID- 2228975 TI - Microcin H47, a chromosome-encoded microcin antibiotic of Escherichia coli. AB - Microcin H47 (MccH47) is a novel microcin antibiotic produced by a natural Escherichia coli isolate. In contrast to all the other colicins and microcins examined to date, which are plasmid encoded, the genes for MccH47 synthesis and immunity are located on the chromosome. These genetic determinants were cloned and shown to extend over a continuous DNA region of ca. 10 kb. PMID- 2228976 TI - Rhizobium meliloti chromosomal loci required for suppression of exopolysaccharide mutations by lipopolysaccharide. AB - Mutants of alfalfa symbiont Rhizobium meliloti SU47 that fail to make extracellular polysaccharide (exo mutants) induce the formation of nodules that are devoid of bacteria and consequently do not fix nitrogen. This Fix- phenotype can be suppressed by an R. meliloti Rm41 gene that affects lipopolysaccharide structure. Here we describe mutations preventing suppression that map at two new chromosomal loci, lpsY and lpsX, present in both strains. Two other lps mutations isolated previously from SU47 also prevented suppression. PMID- 2228977 TI - Methylated DNA in Borrelia species. AB - The DNA of Borrelia species was examined for the presence of methylated GATC sequences. The relapsing-fever Borrelia sp., B. coriaceae, and only 3 of 22 strains of B. burgdorferi contained adenine methylation systems. B. anserina lacked an adenine methylation system. Fundamental differences in DNA methylation exist among members of the genus Borrelia. PMID- 2228979 TI - Regulation of expression of the ftsA cell division gene by sequences in upstream genes. AB - The essential cell division genes ftsQ and ftsA overlap by 1 bp (A. C. Robinson, D. J. Kenan, G. F. Hatfull, N. F. Sullivan, R. Spiegelberg, and W. D. Donachie. J. Bacteriol. 160:546-555, 1984; Q.-M. Yi, S. Rockenbach, J. E. Ward, and J. F. Lutkenhaus. J. Mol. Biol. 184:399-412, 1985). We have previously shown that ftsA can be expressed from a weak promoter located within the ftsQ gene (Robinson et al., J. Bacteriol. 160:546-555, 1984). We report here the effects on ftsA expression of a series of deletions within ftsQ. We find that two regions upstream of the promoter are important in its expression. When both are present, ftsA is expressed, as is also the case when both are absent. The two regulatory elements (O1 and O2) have 9-bp sequences, of which 8 bp are identical. PMID- 2228978 TI - Phenotypic suppression by aminoglycoside antibiotics of mutations blocking erythromycin biosynthesis in Saccharopolyspora erythraea. AB - The presence of a sublethal amount of apramycin, the aminoglycoside antibiotic used as a selectable marker in transformations of Saccharopolyspora erythraea with pKC505 and related plasmids, was found to suppress phenotypically the S. erythraea eryB25 and eryB26 mutations blocking erythromycin biosynthesis in this organism, probably by the effect of mistranslation. PMID- 2228980 TI - Panic and phobic disorders in patients with obsessive compulsive disorder. AB - Obsessive compulsive disorder shares numerous clinical features with other anxiety disorders. To study the relationship between OCD and other anxiety disorders, the authors administered the Structured Clinical Interview for DSM-III to 36 OCD patients. Thirty-nine percent (14) of patients reported a lifetime history of panic attacks, and 14% (5) met DSM-III-R criteria for panic disorder at the time of interview. Fourteen percent (5) met criteria for social phobias, and 19% (7) met criteria for simple phobias. Eighteen patients were treated with clomipramine in doses of at least 100 mg/day for 3 months. Patients with a history of other anxiety disorders responded significantly better to clomipramine. PMID- 2228981 TI - An epidemiologic study of Tourette's syndrome in a single school district. AB - To evaluate the frequency of Gilles de la Tourette's syndrome (TS) in children, 3034 students in three schools in a single school district in greater Los Angeles were monitored frequently over a 2-year period by a school psychologist thoroughly familiar with the symptoms of the disorder. A portion of the cases were also evaluated in a TS clinic. A total of 14 males fulfilled the Tourette Syndrome Association research criteria for definite TS. When corrected for the number of students in special education classes in the monitored schools, the frequency of definite TS in males was 1 in 152. An additional 7 males who differed only in that they were not observed for a full year were termed definite TS less than 1 year. When the two groups were combined, the frequency of definite TS was 1 in 95 for males and 1 in 759 for females. These figures do not include an additional 10 males diagnosed as having definite transient tic disorder, 2 males diagnosed as having probable TS, and 10 males diagnosed as having possible TS. In addition to tics, most of these children had problems with attention span, obsessive compulsive behavior, and learning and/or conduct disorders. Seventy percent of the students with definite TS or definite TS less than 1 year were in special education classes. Twelve percent of the children in special education classes had definite TS or definite TS less than 1 year, and 28% were in one of the diagnostic categories of definite, probable, or possible. All of the 10 definite TS patients that were seen in the clinic had attention-deficit hyperactivity disorder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228982 TI - Clonazepam for the treatment of social phobia. AB - Nine of 11 patients with social phobia of both the generalized and performance type responded to treatment with clonazepam in total daily doses ranging from 0.75 to 3 mg. Only 2 of these 9 had comorbid panic disorder; the benefit for social phobic symptoms appears independent of clonazepam's putative efficacy for panic disorder. PMID- 2228983 TI - An efficacy study of single- versus double-seizure induction with ECT in major depression. AB - Twenty-nine patients with major depression, with and without psychosis, were randomly assigned to bilateral conventional electroconvulsive therapy (ECT) or modified multiple monitored ECT (MMECT) limited to two seizure inductions in a session. From pretreatment to after the fourth treatment session, modified MMECT was associated with more rapid amelioration of depressive symptoms on the basis of blindly rated Hamilton Rating Scale for Depression scores. No medical complications occurred. Sixty-two percent of patients in the modified MMECT group had posttreatment confusion, whereas 15% of patients treated with conventional ECT were confused. Modified MMECT appears to confer some clinical advantage over conventional ECT in the treatment of major depression while carrying an increased risk of treatment-related reversible confusion. PMID- 2228984 TI - Imipramine treatment of panic disorder during pregnancy. AB - Two women with panic disorder who continued to be symptomatic during pregnancy were successfully treated with low doses of imipramine. Plasma drug concentrations were lower than usually required for antidepressant response and remained relatively stable during gestation. Each woman delivered a healthy infant with minimal discomfort from panic symptoms during pregnancy. These cases are illustrative of two women who had a need of and benefited from pharmacotherapy for panic disorder during pregnancy. PMID- 2228985 TI - Selective response to carbamazepine in a case of organic mood disorder. PMID- 2228986 TI - Is maintenance ECT effective? PMID- 2228988 TI - Anxiety: the burden of illness. A symposium held at the annual meeting of the American Psychiatric Association. May 13-16, 1990, New York City. Proceedings. PMID- 2228987 TI - Acute dystonia and fluoxetine. PMID- 2228989 TI - Psychosocial stressors and adjustment disorder: van Gogh's life chart illustrates stress and disease. AB - The life of Vincent van Gogh is illustrative of the natural history of psychosocial stressors and their relationship to a person's states of health and disease. In the author's opinion, there is a lack of such understanding in the current, established criteria for psychosocial stressors in the diagnosis of adjustment disorder. By use of a life chart, which chronologically documents a person's major life events and concomitant health status over his or her life span, a fuller understanding can be reached regarding why an individual becomes ill at a particular time. PMID- 2228990 TI - Anxiety and adjustment disorder: a treatment approach. AB - Adjustment disorder with anxious mood can be difficult to differentiate from other anxiety disorders or personality disorders. Particular care must be taken to distinguish between the reasonable, expected response to psychosocial stressors and the inordinate response that may indicate the diagnosis of adjustment disorder. Once the diagnosis has been established, options for the management of these patients include nonpharmacologic approaches, pharmacotherapy, and combinations of both. The ultimate goals of treatment are to mobilize the patient's stress-coping mechanisms and to prevent the adjustment disorder from developing into another, more chronic condition, such as generalized anxiety disorder. PMID- 2228991 TI - The waking nightmare: an overview of obsessive compulsive disorder. AB - Symptoms of obsessive compulsive disorder (OCD) have been recognized for centuries. Only recently, however, has this disorder been the focus of significant research. OCD remains one of the least understood, least diagnosed, and most disabling of the anxiety disorders. Patients are imprisoned in senseless rituals that siphon off energy that could otherwise contribute to their socioeconomic functioning or personal development. OCD often begins in adolescence and persists in some form throughout adulthood. Recent findings shed light on the epidemiology of OCD and its association with other disorders, and point to a neurophysiologic model involving serotonin. PMID- 2228992 TI - The comorbidity factor: establishing the primary diagnosis in patients with mixed symptoms of anxiety and depression. AB - Accurate diagnosis is the key to effective treatment and long-term management of anxiety and depressive disorders. Numerous studies, however, have established a high incidence of depressive symptoms among patients with anxiety disorders and likewise a significant incidence of anxiety symptoms among patients with unipolar or bipolar disorders. These patients with mixed symptoms will experience a more severe illness, with generally poorer outcome. Careful assessment of the patient's predominant mood, sleep patterns, psychomotor signs, age of onset, family history, pattern of substance use, response to exercise, and extent of psychosocial contact can assist the clinician in making an accurate primary diagnosis. PMID- 2228993 TI - The hidden patient: unrecognized panic disorder. AB - The lifetime prevalence of panic disorder in the United States is 1.5%; nearly 3 times that many Americans experience recurrent panic attacks. Both conditions are associated with diminished well-being, increased alcohol and drug abuse, suicide attempts, and financial dependency, at rates often exceeding those for other psychiatric disorders, including major depression. In spite of these considerable social consequences, panic disorder and panic attacks often go unrecognized. Because their symptoms can present as other medical disorders, including myocardial infarction, temporal lobe epilepsy, Cushing's disease, anemia, hypoglycemia, and lupus, these patients are instead often seen in emergency departments and cardiac and other medical clinics. General practitioners, and especially physicians working in emergency departments, should be alert to the possibility of panic disorder, especially if the patient has a first-degree family member suffering from panic disorder. PMID- 2228994 TI - Managing long-term therapy for panic disorder. AB - Diagnostic criteria for panic disorder have been well defined; but treatment modalities, less so. Combined psychotherapy and pharmacotherapy is the most effective treatment for these disorders. Benzodiazepines, tricyclic antidepressants, monoamine oxidase inhibitors, and other medications have been found effective in clinical studies. Alprazolam, a triazolo analog of the 1,4 benzodiazepine class, recently was proved effective in a cross-national study involving approximately 1700 patients, with minimal side effects. Therapy with the medication is advised for at least 6 months. Medications should be tapered over a prolonged period, at least 8 weeks, especially where high doses are employed. PMID- 2228995 TI - Alpha- and gamma-tocopherol in plasma, red blood cells, and platelets during plasma exchange. AB - The effect of a rapid reduction of plasma lipoproteins on the alpha- and gamma tocopherol levels in plasma, erythrocytes, and platelets was studied. Sixteen successive plasma exchange procedures performed weekly in an adult with heterozygous familial hypercholesterolemia were evaluated. Plasma exchange was done by intermittent flow centrifugation, exchanging one plasma volume against a 4% human albumin solution. Plasma exchange reduced in plasma alpha-tocopherol from 41.5 +/- 8.9 to 23.6 +/- 4.8 mumol/L and gamma-tocopherol from 4.9 +/- 4.1 to 2.4 +/- 2.1 mumol/L, without changing their ratios to total lipids. It diminished alpha-tocopherol in platelets from 12.97 +/- 4.37 to 10.03 +/- 1.78 mumol/10(13) cells and gamma-tocopherol from 1.43 +/- 0.55 to 1.06 +/- 0.41 mumol/10(13) cells, but did not affect erythrocyte tocopherols. The total amount removed per procedure was 47.57 +/- 13.65 mumol for alpha-tocopherol and 4.70 +/- 3.59 mumol for gamma-tocopherol. Plasma exchange increased the number of erythrocytes from 3.67 +/- 0.10.10(12) to 4.05 +/- 0.13.10(12) cells/L, without affecting their volume. Platelet count did not change, but mean platelet volume decreased from 7.7 +/- 0.5 to 6.9 +/- 0.5 fl and platelet distribution width from 15.1 +/- 0.4 to 14.9 +/- 0.5. Thus, plasma exchange reduces plasma alpha- and gamma-tocopherol to the same extent as total lipids, and decreases these tocopherols in circulating platelets, along with a reduction in platelet size and, compared to the change in erythrocyte count, a fall of platelet number.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2228996 TI - Modified method of exchange transfusion in sickle cell disease. AB - The treatment of various complications of sickle cell disease has included red cell exchange in the past, and the development of automated pheresis equipment has greatly simplified such exchanges. Traditionally, the patient's red cells have been exchanged while their plasma was returned to them. Recently, plasma factors have been thought to play a role in the pathogenesis of vasoocclusive events. Therefore, we performed whole blood exchange, which consisted of replacement of the patient's plasma with albumin and saline in addition to the usual replacement of erythrocytes. A total of 32 whole blood exchanges were performed on 12 patients with a variety of complications of their disease. The procedure was done using standard pheresis equipment and was relatively simple to perform. There were no serious complications and the clinical outcome was good with 10 out of 12 patients experiencing improvement. PMID- 2228997 TI - Thrombotic complications of subclavian apheresis catheters in cancer patients: prevention with heparin infusion. AB - Twenty-two silicone rubber apheresis catheters were placed into the subclavian veins of 18 cancer patients to allow serial leukapheresis for collection of circulating hematopoietic stem cells. The tips of the catheters were placed in the innominate vein to avoid reinfusion of citrate into the right atrium and the resulting tendency to cardiac arrhythmias. Sixteen catheters were placed without prophylactic anticoagulation. Anticoagulation was prematurely discontinued in one patient because of the inconvenience of the portable heparin infusion pump. Six of these 17 catheters developed venographically proven thrombotic complications and five others had presumed thrombosis-related access failure or caused symptoms of venous obstruction, but confirmation of the presence of a thrombus with venography was not obtained. Three catheters spontaneously withdrew from the vein, one during urokinase infusion for thrombosis. Only three catheters had uncomplicated apheresis courses. Prophylactic heparin infusions via portable infusion pumps were given after placement of six catheters. As long as the heparin infusions were continued all patients had uncomplicated apheresis courses. One patient's heparin was prematurely discontinued. Within 3 days of its discontinuance, radiographically proven thrombotic catheter occlusion occurred. Patients given heparin were less likely to develop complications (P less than 0.001). No unexpected complications of apheresis were encountered as a result of the use of these catheters. Silicone rubber subclavian catheters can be used for peripheral stem cell collection but have a high frequency of thrombotic complications. Systemic anticoagulation with heparin can minimize the likelihood of these complications. PMID- 2228998 TI - Plasma exchange in endocrine ophthalmopathy. AB - We studied the effects of intensive plasma exchange on endocrine ophthalmopathy in 12 patients with Graves' disease and one with Hashimoto's thyroiditis. All patients were euthyroid at the time of plasma exchange. All but five had concomitant treatment with azathioprine. Each patient had a treatment period consisting of six plasma exchanges performed in 2-3 weeks; two patients were treated in two periods. Each time a mean of 2.4 liters plasma was exchanged. There was a prompt reduction in the concentration of circulating immune complexes and/or thyrotropin receptor antibodies following plasma exchange. Six of the 13 patients improved their proptosis; their median duration of eye symptoms before treatment was less than 8 months. In patients suffering from eye symptoms for more than 1 year improvement was rare. Overall the Hertel values were 24.1 +/- 4.4 (SD) before and 22.8 +/- 3.4 after plasma exchange for the left eyes (P = 0.07) and 23.8 +/- 4.0 before and 23.0 +/- 3.8 after for the right eyes (P = 0.09). Nine patients altogether improved their ophthalmopathy index and periorbital oedema. In patients with disabling endocrine ophthalmopathy plasma exchange may sometimes be of value to induce a relief of the ophthalmopathy; when it is used it should be instituted before fibrotic changes occur. We suggest that concomitant immunosuppressive drugs should be given to prevent rebound phenomenon induced by plasma exchange. To establish the role of plasma exchange in the treatment of endocrine ophthalmopathy controlled studies should be performed. PMID- 2228999 TI - Clinical studies on adequate dosage of heparin during immunoadsorption with membrane plasmapheresis. AB - Heparin has been used as an anticoagulant during hemodialysis and plasmapheresis. Recently, immunoadsorption with membrane plasmapheresis (IAP) has been used for treatment of myasthenia gravis and multiple sclerosis. Ten patients were examined. Plasma heparin levels were studied before IAP, 30 minutes, 60 minutes, 90 minutes, and 120 minutes after the start of IAP, and at the end of IAP. Prothrombin time, activated partial thromboplastin time (APTT), bleeding time, plasma fibrinogen levels, fibrin degradation products, and complete blood count were measured pre- and post-IAP. In general, plasma heparin levels lower than 1 IU/ml during plasmapheresis are adequate. The dosage of 40 IU/kg/hr of heparin administered during IAP resulted in plasma heparin levels lower than 1 IU/ml. APTT pre-IAP (36.8 +/- 3.4 sec) were nearly one-half values of APTT post-IAP (6.2 +/- 9.70 sec). In conclusion, 40 IU per kg of the body weight per hour is an acceptable dose of heparin during IAP. PMID- 2229000 TI - Computerization of plateletpheresis quality control records with a commercially available spreadsheet program. AB - Many apheresis units lack the resources to acquire customized computer software for record keeping. We have adapted a commercially available "spreadsheet" program (Lotus 1-2-3) to aid in quality control activities for plateletpheresis. Data are entered in a grid pattern wherein each donation occupies one row and successive columns contain numerical data derived from the donation. The last two columns contain formulas that calculate yield and collection efficiency from values entered in preceding columns. The program runs on an IBM PC or equivalent with 512 K RAM; the combined cost of a computer and software is currently under $2,000.00. Data entry requires fewer keystrokes per record than computation of yield and efficiency with a calculator, and creates an inclusive permanent record for future analysis. Data sorting and statistical functions allow rapid identification of incomplete records, and derivation of average platelet yield and/or collection efficiency for any time period of interest. The program also facilitates determining the proportion of donations that fall below any chosen cutoff. Performance characteristics of a particular instrument or operator can be assessed easily by isolating the pertinent records and analyzing them separately. The system will thus accomplish a variety of quality control activities, including those mandated by licensing agencies. It can be implemented by apheresis personnel with limited "computer literacy" and is superior to manual tabulation of quality control data in both ease of data entry and facility of analysis. PMID- 2229001 TI - Therapeutic plasmapheresis and protein A immunoadsorption in malignancy: a brief review. AB - Plasmapheresis is being used with considerable frequency in the management of malignant and non-malignant disorders. More recently, staphylococcal Protein A immunoadsorption has been employed in similar clinical situations. In patients with malignancy, plasmapheresis has been shown to produce alterations in plasma proteins, decrease circulating immune complexes, remove "specific" and "non specific" blocking factors, change immune reactivity, and affect monocyte function. Partial responses have been reported in a small number of patients with carcinoma of lung, colon, and breast following plasmapheresis. In addition, there are reports of favorable responses in patients with melanoma, head and neck tumors, lymphomas, leukemias, and Kaposi's sarcoma in acquired immune deficiency. All these responses were partial and brief, and the treatment did not alter the course of the disease. Plasmapheresis has been useful in the management of hyperviscosity and occasionally of paraneoplastic syndromes. It may also have a role in the treatment of thrombotic thrombocytopenic purpura associated with mitomycin-C therapy. Protein A immunoadsorption, by which circulating immune complexes are selectively removed, can activate the complement system, increase blastogenic responses, and increase the natural killer cell activity. It has been shown to produce partial responses in breast and colon cancer, as well as Kaposi's sarcoma in acquired immune deficiency. It may have a useful role to play in the management of mitomycin-C-associated thrombotic thrombocytopenic purpura. Both plasmapheresis and Protein A immunoadsorption should be considered investigational interventions at this time. Toxicity of plasmapheresis, though uncommon, can be serious and may rarely be fatal. Toxicity of Protein A immunoadsorption is mild, consisting mainly of influenza-like symptoms and rash. PMID- 2229002 TI - The cAMP-dependent protein kinase in sea urchin sperm tails: association of the enzyme with the flagellar axonemes. AB - When sea urchin spermatozoa were treated with a Triton X-100 solution, cAMP dependent protein kinase (cA-kinase) activity was extracted. Further extraction with Triton X-100 of axonemes isolated from the Triton-extracted sperm again released a considerable amount of the cA-kinase activity. The activity which remained after extraction three times with Triton X-100 was released by treatment with a low salt solution. These activities found in the various extracts were likely to be due to the same cA-kinase, which was a mammalian type II-like enzyme. The cA-kinase activity that remained in the axonemes after the first Triton X-100 extraction may be involved in the regulation of flagellar movement in the Triton-extracted sperm. PMID- 2229003 TI - Steroid transhydrogenase activity of 3-ketosteroid-delta 1-dehydrogenase from Nocardia corallina. AB - 3-Ketosteroid-delta 1-dehydrogenase from Nocardia corallina catalyzes transhydrogenation of 3-keto-4-ene-steroid to 3-keto-1,4-diene-steroid e.g., progesterone to 1,4-androstadiene-3,17-dione. The reaction proceeded linearly at first and then soon slowed down owing to equilibration. The turnover number of this reaction was of the same magnitude as that of the dehydrogenation of 3-keto 4-ene-steroid. The pH optimum was 8.4, which is lower than that of the dehydrogenase reaction. The enzyme has a wide specificity for hydrogen acceptor steroids. The Km' and Kmax' values for these steroids and the values of the corresponding 3-keto-4-ene-steroids were compared. Kinetic studies of the steroid transhydrogenase reaction demonstrated a typical ping-pong mechanism. The enzyme oxidized 1,2-tritiated progesterone and transferred the tritium atoms to the reaction product, 4-androstene-3,17-dione, and water. Transhydrogenation in D2O resulted in the incorporation of a deuterium atom into the C2-position of 4 androstene-3,17-dione. The results indicate that the enzyme catalyzes C1, C2 trans axial abstraction of hydrogen atoms from progesterone, transfer of the 1 alpha-hydrogen to the C1-position of 1,4-androstadiene-3, 17-dione and release of the 2 beta-hydrogen to water. Reaction schemes based on the experimental results are proposed. The enzyme also catalyzes the reduction of 3-keto-1,4-diene steroids with reduced benzyl viologen. PMID- 2229004 TI - Complete amino acid sequence of rat kidney ornithine aminotransferase: identity with liver ornithine aminotransferase. AB - The complete amino acid sequence of rat kidney ornithine aminotransferase [EC 2.6.1.13] is presented. The 404-residue sequence was determined by analysis of peptides generated by digestion of the S-carboxyamidomethylated protein with CNBr, Achromobacter protease I, arginylendopeptidase, or Staphylococcus aureus V8 protease. Mueckler and Pitot have reported the amino acid sequence of the rat liver enzyme (440 residues) as predicted from the nucleotide sequence of the cDNA [Mueckler, M.M. & Pitot, H.C. (1985) J. Biol. Chem. 260, 12993-12997]. The amino acid sequence of the rat kidney enzyme presented herein coincides with residue 36 (Gly) through 440 (Phe) of the predicted precursor protein, indicating that the liver and kidney enzymes are identical, and that the enzyme is processed at the amino-terminal region after translation. PMID- 2229005 TI - Amino acid sequence of a lectin from Japanese frog (Rana japonica) eggs. AB - The complete amino acid sequence and the location of disulfide bonds of a lectin from Japanese frog (Rana japonica) eggs, which specifically agglutinates transformed cells, are presented. The sequence was determined by analysis of peptides generated by digestion of the S-carboxyamidomethylated protein with Achromobacter protease I, or chymotrypsin, and by chemical cleavage with BNPS skatole or cyanogen bromide. The lectin is a single-chain protein consisting of 111 residues, with a pyroglutamyl residue at the amino terminus. Four disulfide bonds link half-cystinyl residue 19 to 72, 34 to 82, 52 to 97, and 94 to 111. The sequence and the location of the disulfide bonds are highly homologous to those of bull frog (Rana catesbeiana) egg S-lectin. They are also homologous to human angiogenin, a tumor angiogenesis factor, and a family of pancreatic ribonucleases. PMID- 2229006 TI - Kinetics of the hydrolysis of mixed micelles of dipalmitoyllecithin with triton X 100 catalyzed by a phospholipase A2 from the venom of Agkistrodon halys blomhoffii. AB - The pH dependence of kinetic parameters for the hydrolysis of mixed micelles of 1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine (diC16PC) with Triton X-100, catalyzed by the intact and the N-terminal alpha-NH2-modified phospholipases A2 (PLA2s) of Agkistrodon halys blomhoffii, was studied at 25 degrees C and ionic strength 0.1 in the presence of saturating amounts of Ca2+. The pH dependence of the kinetic parameters for the hydrolysis of monodispersed diC6PC, catalyzed by the modified enzyme, was also studied under the same conditions, and the data were compared with the previous results for the intact enzyme [Teshima, K. et al. (1986) J. Biochem. 100, 1655-1662]. The pK values of the catalytic group, His 48, and Tyr 52 were found to shift from 5.55 to 7.00 and from 10.50 to 11.50, respectively, on binding of the micellar substrates to the enzyme. On the other hand, no participation of these ionizable groups was observed for the binding of the monodispersed substrate. On the basis of the present finding and the X-ray crystallographic studies on bovine pancreatic PLA2 [Dijkstra, B.W. et. al. (1981) J. Mol. Biol. 147, 97-123] and on a PLA2 of Crotalus atrox venom [Brunie, S. et al. (1985) J. Biol. Chem. 260, 9742-9749], the hydrogen-bonding of Tyr 73, which is involved in the lipid-water interface recognition site, to His 48 and Tyr 52 in the active center was strongly suggested to be important for the hydrolysis of micellar substrates. PMID- 2229007 TI - Induction in mouse peritoneal macrophages of 34 kDa stress protein and heme oxygenase by sulfhydryl-reactive agents. AB - The synthesis of 34-kDa stress protein was enhanced, with a simultaneous increase in heme oxygenase activity, when mouse macrophages were exposed to diethylmaleate or sodium arsenite. After 7 h of exposure to the sulfhydryl agents, the 34-kDa protein was the most actively synthesized protein. Immunoblot analysis showed that the induced 34-kDa protein reacted with an antibody raised against bovine heme oxygenase. Cadmium ions or 1-chloro-2,4-dinitrobenzene also induced the 34 kDa protein which reacted with the antibody. Treatments of the cells with buthionine sulfoximine or hydrogen peroxide weakly induced the protein, while diamide treatment or heat shock was without effect. These results are consistent with our previous findings that heavy metal ions including arsenite and cadmium ions induce heme oxygenase (32-kDa stress protein) in human cell lines [Taketani, S., Kohno, H., Yoshinaga, T., & Tokunaga, R. (1989) FEBS Lett. 245, 173-176], and also suggest that the formation of glutathione conjugate with sulfhydryl-reactive agents may mediate the induction of the stress protein in mouse peritoneal macrophages. PMID- 2229008 TI - Purification and characterization of rat pulmonary cytochrome P-450. AB - The pulmonary cytochrome P-450, P450 L-2, was purified 460-fold from pulmonary microsomes of untreated male rats. Its specific content was 10.6 nmol/mg of protein. The monomeric molecular weight was 54,000 on SDS-polyacrylamide gel electrophoresis. The CO-reduced absorption maximum of P450 L-2 was at 451 nm, and the oxidized heme iron appeared to be in the low-spin state, as deduced from the Soret maximum at 421 nm. P450 L-2 had high lauric acid omega- and (omega-1) hydroxylation activities, but low prostaglandin A1 omega- and (omega-1) hydroxylation activities. It catalyzed the O-dealkylation of 7-ethoxycoumarin, but was not efficient in the hydroxylation of testosterone or the N-demethylation of aminopyrine. The NH2-terminal amino acid sequence of P450 L-2 was V-L-N-F-L-X P-X-L (X being an unidentified residue). The catalytic properties of P450 L-2 resembled those of P450 K-5, the major rat renal cytochrome P-450. However, anti P450 K-5 antibody did not cross-react with P450 L-2, and these forms had different NH2-terminal sequences. To judge from the results of NH2-terminal sequence analysis, P450 L-2 seems to be placed in the IVB gene family. Also, P 450 IIB1 was detected by immunoblotting in one of the peaks on ion-exchange HPLC during the purification of P450 L-2, suggesting the presence of P-450 IIB1 in rat pulmonary microsomes. PMID- 2229009 TI - Sexual response of Saccharomyces cerevisiae: phosphorylation of yeast glyoxalase I by a cell extract of mating factor-treated cells. AB - The phosphorylation of glyoxalase I was observed when the phosphatase-treated enzyme was incubated in the presence of [gamma-32P]ATP and a cell extract prepared from alpha-type yeast cells which had been treated with the culture supernatant of a-type yeast cells. The phosphorylated protein was identified as glyoxalase I by using anti-glyoxalase I rabbit immunoglobulin G. PMID- 2229010 TI - Inhibitory effect of pseudo-aminosugars on oligosaccharide glucosidases I and II and on lysosomal alpha-glucosidase from rat liver. AB - We examined the inhibitory effect of three pseudo-aminosugars (validamine, valienamine, and valiolamine), which were isolated from the broth of Streptomyces hygroscopicus, on the oligosaccharide-processing glucosidases I and II involved in glycoprotein biosynthesis in rat liver. Both glucosidases I and II were inhibited to the same extent by the pseudoaminosugars, and valiolamine had a more potent inhibitory activity than validamine or valienamine. A 50% inhibition of valiolamine was observed at 12 microM for glucosidase I and glucosidase II activities acting respectively on the substrates Glc3Man9GlcNAc2 and p nitrophenyl alpha-D-glucopyranoside. Further, in order to investigate further the ability of valiolamine to inhibit glucosidase I, reaction products were analyzed by gel filtration on a Bio-Gel P-4 column. We also compared the inhibitory action of these pseudo-aminosugars on the acid alpha-glucosidase of rat liver lysosomes. They competitively inhibited the hydrolysis of both substrates, maltose and glycogen. Valiolamine again had a more potent lysosomal alpha-glucosidase inhibitory activity than the other two. The Ki values of valiolamine for the hydrolysis of maltose and glycogen were 8.1 and 11 microM, respectively. Valiolamine is a particularly effective inhibitor of oligosaccharide glucosidases I and II and of lysosomal alpha-glucosidase. Hence valiolamine might be useful as a research tool in investigations of carbohydrate metabolism. PMID- 2229012 TI - Tissue specificity of tropomyosin from the crayfish, Cambarus clarki. AB - The molecular heterogeneity and tissue specificity of crustacean tropomyosin were investigated, using muscle and nonmuscle tissues from the crayfish, Cambarus clarki. In muscle, three types of tropomyosin isoforms were found on two dimensional gel electrophoresis. One of them was specific to cardiac muscle, and the other two were shared by skeletal and visceral muscles. In nonmuscle tissues, four types of isoforms were found on two-dimensional gel electrophoresis and in immunoreplica tests using an antiserum against crayfish skeletal muscle tropomyosin. Two of them were common to the muscle isoforms, but the other two were not detected in muscles. Furthermore, nonmuscle tissues contained several peculiar isoforms, the electrophoretic mobilities of which were considerably higher than those of the other isoforms mentioned above. When tropomyosin was purified from the mid-gut gland, these isoforms with high mobilities were found in the crude tropomyosin preparation. These results showed that the crayfish tropomyosin was heterogeneous and that the isoforms were distributed in a tissue specific manner, like vertebrate tropomyosin. However, the results did not coincide with those of our previous study on horseshoe crab tropomyosin, which showed molecular heterogeneity but no tissue specificity. In view of the difference in the isoform distributions between the two major groups (Crustacea and Merostomata) of Arthropoda, the significance of the tissue specificity of tropomyosin isoforms was discussed. PMID- 2229011 TI - Structure of an allergenic pentasaccharitol, Gp-1 beta-b6, isolated from a sea squirt antigen, Gi-rep, as a minimum structural unit responsible for its allergenicity. AB - An allergenic pentasaccharitol, Gp-1 beta-b6, was isolated as a minimum structural unit responsible for the allergic reaction in skin of patients with sea squirt allergy from a saccharitol fraction, Gp-1 beta-b, that had been liberated by beta-elimination from a glycopeptide in a Pronase digest of a sea squirt antigen, Gi-rep. Methylation/GC-MS and FAB-MS analyses indicated the sugar sequence of Gp-1 beta-b6 to be GalNAcl----2Fucl----(GalNAc1----) 3,4GlcNAc1--- 3GalNAc-ol. To analyze the structure in more detail, Gp-1 beta-b6 was labeled with p-aminobenzoic acid ethyl ester (ABEE), i.e., the reducing terminal 3-O substituted GalNAc-ol of the saccharitol was oxidized to 2-O-substituted L-ThrNAc with equimolar periodate, and the resultant aldehyde was labeled with ABEE by reductive amination. The ABEE-labeled Gp-1 beta-b6 was subjected to sequential exoglycosidase digestion with beta-N-acetylhexosaminidase, alpha-N acetylgalactosaminidase, and alpha-fucosidase, and the digests were chromatographed on an HPLC column of TSK gel Amide 80. From the results of the HPLC, methylation/GC-MS, and FAB-MS analyses of the digests of the labeled substrate, the structure of Gp-1 beta-b6 was determined to be GalNAc alpha 1--- 2Fuc alpha 1----3(GalNAc beta 1----4)GlcNAc beta 1----3GalNAc-ol. Enzymatic elimination of either the non-reducing terminal beta-GalNAc or the non-reducing terminal alpha-GalNAc led to inactivation of the allergenic pentasaccharitol. Accordingly, it is possible that the allergenic saccharitol contains two disaccharide units as the allergy-specific epitopes, one GalNAc alpha 1----2Fuc alpha 1---- and the other GlcNAc beta 1----4GLcNAc beta 1----. PMID- 2229013 TI - Characterization of the Fc receptor for IgG2 on guinea pig polymorphonuclear leukocytes by the use of a monoclonal antibody. AB - Guinea pig polymorphonuclear leukocytes (PMNs) possess two distinct types of Fc gamma receptor (Fc gamma R): Fc gamma 1/gamma 2R for both IgG1 and IgG2, and Fc gamma 2R for IgG2 alone. The Fc gamma 2R was previously shown to differ antigenically from homologous macrophage (M phi) Fc gamma 2R by the use of a monoclonal antibody to M phi Fc gamma 2R (VIIAI IgG1), though the Fc gamma 1/gamma 2R cross-reacts with a monoclonal antibody to homologous M phi Fc gamma 1/gamma 2R (VIA2 IgG1). Recently, we obtained a monoclonal antibody (MP-2) secreted by a hybridoma prepared by fusion of the splenic cells of mice immunized with guinea pig PMNs with a myeloma cell line. This antibody completely inhibited both the Fc gamma 2R-mediated rosette formation of PMNs with IgG2 antibody sensitized sheep erythrocytes and the Fc gamma 2R-mediated binding of ovalbumin (OA)-complexed IgG2 antibody to PMNs. When the antigen of MP-2 was isolated by affinity chromatography with the antibody-Sepharose, it gave a single band with a molecular weight of 120,000 on SDS-PAGE. The number of antigen molecules per PMN was estimated to be 9 X 10(4) by measuring the binding of 125I-MP-2 Fab. This value was essentially the same as that obtained by measuring the binding of OA complexed IgG2 antibody to the PMNs treated with the Fab' of VIA2 IgG1. These results strongly suggest that MP-2 is a monoclonal antibody to PMN Fc gamma 2R. PMID- 2229014 TI - Amino acid sequence at the reactive site of rabbit alpha-1-antiproteinases. AB - Rabbit alpha-1-antiproteinases S and F were treated with trypsin, chymotrypsin, Staphylococcus aureus protease V8, and thermolysin, and the liberated peptides encompassing the reactive region of the respective inhibitors were separated and sequenced. The reactive center of the F form was methionine, and the residues from P3 to P'1 (Ile-Pro-Met-Ser) were the same as those of human alpha-1 antiproteinase. The S form, on the other hand, was found to be a mixture of two distinct proteins (S-1 and S-2), and their reactive centers (P1-P'1) were Ser-Ser and Tyr-Ser, respectively. Seven out of 17 amino acids in the F form and 7 out of 16 in the S-1 form were the same as the corresponding residues of human alpha-1 antiproteinase, while 5 of 10 residues in the S-2 form were the same as those of the human inhibitor. Ten out of 16 residues were the same between the F and the S 1 forms, whereas the sequence P1 to P'3 of the S-2 form (Tyr-Ser-Met-Pro) was the same as the corresponding residues of mouse alpha-1-antiproteinase. PMID- 2229015 TI - Kinetics of hydroperoxide degradation by NADP-glutathione system in mitochondria. AB - Hydroperoxide decomposition by the NADP-glutathione system in rat liver mitochondria was analyzed. Mitochondria were found to contain high concentrations of the reduced form of glutathione (GSH) (4.32 +/- 0.50 nmol/mg) and NADPH (4.74 +/- 0.64 nmol/mg), and high activities of glutathione peroxidase and reductase. In the initial phase of the reaction, the rate of hydroperoxide decomposition was proportional to both the GSH level and the activity of GSH peroxidase. However, in the later steady state, the step of NADP reduction was rate-limiting, and the overall reaction rate was independent of the initial concentration of GSH, and activities of glutathione peroxidase and reductase. Some GSH was released from mitochondria during incubation, but the rate of the decomposition could be simply expressed as kappa [GSH]/2, where kappa is the first-order rate constant of the peroxidase and [GSH] is the intramitochondrial level of GSH in the steady state. The rate of the reaction in the steady state was also dependent on the NADPH level, its reciprocal being linearly correlated with [NADPH]-1. The rate of decomposition of hydroperoxide was influenced by the respiratory state. During state 3 respiration, the rate was greatly depressed, but was still considered to exceed by far the rate of physiological generation of hydroperoxide. PMID- 2229016 TI - High-performance liquid chromatography-mass spectrometry of glycosphingolipids: II. Application to neutral glycolipids and monosialogangliosides. AB - We previously reported a method of high-performance liquid chromatography-fast atom bombardment mass spectrometry (HPLC/FAB/MS) for the structural characterization of molecular species of GlcCer and IV3 beta Gal-Gb4Cer [M. Suzuki et al. (1989) J. Biochem. 105, 829-833]. In this paper, we report a modification of this HPLC/FAB/MS method, which was used for the separation and characterization of neutral glycosphingolipids (GlcCer, LacCer, Gb3Cer, Gb4Cer, and IV3 alpha GalNAc-Gb4Cer) and monosialogangliosides [GM3(NeuAc or NeuGc), GM2 (NeuAc or NeuGc), and GM1 (NeuAc or NeuGc)]. Mixtures of the purified neutral glycolipids and monosialogangliosides were subjected to HPLC on a silica gel column, with programmed elution with isopropanol-n-hexane-water, with or without ammonium hydroxide. In order to obtain mass spectra and mass chromatograms of individual components, effluent from the HPLC column was mixed with a methanol solution of triethanolamine, which was used as the matrix for the FAB ionization, and one-thirtieth of the effluent mixture was introduced into a mass spectrometer through a frit interface. A mixture of the five neutral glycolipids, 5 micrograms of each, gave five peaks on a mass chromatogram obtained by monitoring of the corresponding major pseudo-molecular ions. A mixture of the six monosialogangliosides, 5 micrograms of each, gave six peaks on a mass chromatogram obtained by monitoring of the major pseudo-molecular ions, indicating that GM3, GM2, and GM1 were clearly separated, and that separation due to differences in sialic acid species was also achieved. In the mass spectra of the neutral glycolipids and monosialogangliosides, pseudo-molecular ions and fragment ions due to the elimination of sugar moieties were clearly detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229017 TI - Primary structure of human plasma glutathione peroxidase deduced from cDNA sequences. AB - Human plasma glutathione peroxidase (GSHPx) has been shown to be a selenium containing enzyme immunologically distinct from cellular GSHPx. Oligonucleotide probes, based on the partial amino acid sequence of plasma GSHPx, were synthesized and used to screen a human placenta cDNA library. Nucleotide sequence analysis of the obtained clones revealed that GSHPx consisted of a 678-base pair open reading frame coding for a 226-amino acid polypeptide with a Mr of 25,389. About 50% of the deduced amino acid sequence was confirmed by partial amino acid sequencing of the peptides in a lysine endopeptidase-digest of the purified enzyme. The amino acid sequence exhibited only 44% homology with that of human cellular GSHPx. Northern blot analysis revealed a single transcript of 2.2 kilobases in the poly(A)+ RNA fractions of human placenta and HepG2 (a human hepatic cell line), but not that of human liver and endothelial cells. PMID- 2229018 TI - Human aldolase A of a hemolytic anemia patient with Asp-128----Gly substitution: characteristics of an enzyme generated in E. coli transfected with the expression plasmid pHAAD128G. AB - Aldolase A derived from a hemolytic anemia patient with aldolase A deficiency was shown to have an amino acid substitution of glycine for aspartic acid at the 128th position (Asp-128) in the enzyme [Kishi et al. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8623-8627]. We constructed an Escherichia coli expression plasmid, pHAAD128G, which carries the mutant aldolase A [aldolase A(D-G)] cDNA, and the enzyme generated in E. coli transfected with the expression plasmid was purified and characterized. Conversion of Asp to Gly at the 128th position in the enzyme rendered the enzyme thermolabile and susceptible to tryptic digestion. CD spectra analysis also revealed that the mutant enzyme had a remarkable conformation change with a decrease of regular form in the molecule. Addition of glycerol or some other polyalcohols during thermal treatment protected this altered enzyme (but not the normal enzyme) against denaturation and activity decrease. In order to determine the function of the amino acid residue at the 128th position, two artificial mutant enzymes with the substitutions of Glu for Asp [aldolase A(D-E)] and Ser for Asp [aldolase A(D-S)], respectively, at the position were constructed by site-directed mutagenesis and characterized. These analyses demonstrated the necessity for Asp to be present at the 128th residue in order for this enzyme to be thermally stable. PMID- 2229019 TI - Three-dimensional structure of an alpha-amylase inhibitor HAIM as determined by nuclear magnetic resonance methods. AB - The three-dimensional structure of an alpha-amylase inhibitor, HAIM, composed of 78 amino acids, was analyzed by two-dimensional NMR techniques. Sequence-specific assignments were made for the amino acid residues from Ile-6 to Cys-72. Distance geometry analysis of the interresidue NOEs revealed that the HAIM molecule consists of two beta-sheets, as is the case in a homologous alpha-amylase inhibitor, Tendamistat, though one of its beta-strands is much shorter than that of Tendamistat. The combination of molecular modeling from Tendamistat and distance geometry analysis was confirmed to be useful for our purpose. PMID- 2229020 TI - Characterization of cyanide-resistant respiration and appearance of a 36 kDa protein in mitochondria isolated from antimycin A-treated Hansenula anomala. AB - Mitochondria exhibiting cyanide-resistant respiration were isolated from Hansenula anomala which had been incubated in the presence of antimycin A to induce cyanide-resistant respiration. The cyanide-resistant respiration in isolated mitochondria was not inhibited by antimycin A or myxothiazol, suggesting that the branching of the pathway from the normal cyanide-sensitive pathway takes place at the coenzyme Q level. Analysis of mitochondrial proteins by sodium dodecyl sulfate gel electrophoresis indicated that a 36 kDa protein was induced by antimycin A treatment of the yeast. It is suggested that this protein is a component of the cyanide-resistant respiratory pathway. PMID- 2229021 TI - Gangliosides from the eggs of the sea urchin, Anthocidaris crassispina. AB - NeuGc alpha 2-6Glc beta 1-1Cer (M5 ganglioside) and HSO3-8NeuGc alpha 2-6Glc beta 1-1Cer (T1 ganglioside) were purified by column chromatographies with DEAE Sephadex A-25 and silicic acid from the eggs of the sea urchin, Anthocidaris crassispina. Their chemical structures were determined by gas-liquid chromatography, methylation analysis, enzymatic hydrolysis, negative-ion fast atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy. Long-chain base compositions of both gangliosides were almost identical: all the long-chain bases were phytosphingosines, and C18 phytosphingosine accounted for more than 95% of them. Fatty acid compositions were also very similar: the main fatty acids were 22:1, 23:1, 24:1, and their 2 hydroxylated forms, and the 2-hydroxy fatty acids amounted to 65.3 and 74.3% of the fatty acids in M5 and T1 gangliosides, respectively. Proton nuclear magnetic resonance spectroscopic study revealed a downfield-shifted H8 proton signal of NeuGc residue in T1 ganglioside, in agreement with the presence of sulfate ester at the C8 position. PMID- 2229022 TI - Characterization of gene organization and generation of heterogeneous mRNA species of rat ISK protein. AB - The ISK protein is a novel, probably epithelial potassium channel which differs from conventional potassium channels in its structure, electrophysiology, and tissue distribution. In this investigation, we isolated and analyzed genomic and cDNA clones coding for the rat ISK protein to characterize the structural organization and expression pattern of the ISK protein gene. This analysis, together with primer extension and RNase protection experiments, indicated that the ISK protein mRNA is initiated from two different upstream exons and then encoded by an uninterrupted downstream exon covering the protein-coding and the 3'-untranslated regions of the mRNA. RNA blot hybridization analysis showed additional generation of several large species of mRNAs which result from inclusion of a part of the intron sequence and the 3'-flanking region of the ISK protein gene. Thus, the single ISK protein gene is involved in the production of multiple species of mRNAs through a variety of cellular mechanisms including transcription initiation at different sites, alternative RNA splicing, and polyadenylation at different sites. The heterogeneity of the ISK protein mRNAs may be associated with the emergence of the functional and regulatory diversity observed for potassium ion permeation in epithelial cells. PMID- 2229023 TI - Presequence does not prevent folding of a purified mitochondrial precursor protein and is essential for association with a reticulocyte cytosolic factor(s). AB - Ornithine carbamoyltransferase (OTC; subunit, 36,000 Da) [EC 2.1.3.3] is initially synthesized as a precursor (pOTC) with a transient NH2-terminal presequence of 32 amino acid residues, then is imported posttranslationally nto the mitochondrial matrix. We expressed rat pOTC in Escherichia coli, purified it in a denatured form, and showed that could be transported into isolated mitochondria in the presence of rabbit reticulocyte lysate [Murakami et al. (1988) J. Biol. Chem. 263, 18437-18442]. In order to compare the properties of the precursor and mature form of OTC, the rat mature OTC was synthesized in E. coli and purified. The recombinant OTC represented about 5% of the total bacterial protein and was present in both the supernatant and precipitate of the disrupted bacteria. The OTC, extracted from the precipitate with 8 M urea or 6 M guanidine.HCl, was essentially homogeneous, as judged by SDS-PAGE. When guanidine.HCl-denatured mature OTC was diluted and incubated at 0 degrees C for 40-60 h, it was reactivated to a specific activity of 170 mumol/min/mg protein at 37 degrees C (18% of that of the purified mature enzyme). Guanidine.HCl-denatured pOTC was activated to a specific activity of 125 mumol/min/mg protein under similar conditions. The native and reactivated OTC sedimented with an s20.w value of 6.2S, whereas the activated pOTC sedimented with an s20.w of 5.2S. The activated pOTC was more unstable than the reactivated OTC at 50 degrees C. These observations indicate that the presequence does not prevent pOTC from folding into an enzymatically active trimeric form, although the pOTC trimer appears to be less compact than the mature trimer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229024 TI - Molecular cloning and sequencing of the cDNA of rat alpha 1-protease inhibitor and its expression in COS-1 cells. AB - A cDNA clone for alpha 1-protease inhibitor (pc alpha 1P1212) was isolated from a lambda ZAP rat liver cDNA library. The 1.4 kb cDNA insert of pc alpha 1P1212 contained an open reading frame that encodes a 411-residue polypeptide (46,125 Da), in which a signal peptide of 24 residues was identified by comparison with the NH2-terminal sequence of the purified protein. Three potential sites for N linked glycosylation were found in the molecule, accounting for the difference in molecular mass between the predicted form and the purified protein (56 kDa). The deduced primary structure of rat alpha 1-protease inhibitor showed 68.5% homology to that of the human inhibitor. We then constructed the expression plasmid pSV2 alpha 1PI from pSV2-gpt and pc alpha 1P1212, and transfected it into COS-1 cells. The transfected cells synthesized a molecule which was precipitated with anti (rat alpha 1-protease inhibitor)-IgG and had the same molecular size as that of the inhibitor produced by rat hepatocytes. PMID- 2229025 TI - Tachyplesins isolated from hemocytes of Southeast Asian horseshoe crabs (Carcinoscorpius rotundicauda and Tachypleus gigas): identification of a new tachyplesin, tachyplesin III, and a processing intermediate of its precursor. AB - Tachyplesins and their analogs are antimicrobial peptides composed of 17 or 18 amino acid residues present abundantly in acid extracts of hemocyte debris of horseshoe crabs. We purified here tachyplesin isopeptides from hemocytes of two species of Southeast Asian horseshoe crabs, Carcinoscorpius rotundicauda and Tachypleus gigas, and determined their amino acid sequences. The major tachyplesin isolated from both species was identified, respectively, as tachyplesin I, which had previously been found in hemocytes of the Japanese horseshoe crab (Tachypleus tridentatus). The yield from both species was very high (more than 70 mg per 100 g wet weight of hemocytes), i.e., comparable with that from T. tridentatus. In addition to tachyplesin I, a new tachyplesin isopeptide, named tachyplesin III, was also isolated from T. gigas hemocytes, in which an arginine replaced the 15th lysine of tachyplesin I. The carboxyl terminal residue of the isolated tachyplesins I and III was confirmed, respectively, to be an arginine alpha-amide by chemical analysis. Furthermore, a tachyplesin peptide derivative with a carboxyl-terminal extension of glycine lysine was newly found in the hemocytes of C. rotundicauda. It appeared to be an intermediate derived from a tachyplesin precursor during processing to the mature form. PMID- 2229026 TI - Evidence for in vivo synthesis of thiamin triphosphate by cytosolic adenylate kinase in chicken skeletal muscle. AB - We showed previously that cytosolic adenylate kinase (AK1) purified from pig skeletal muscle catalyzes in vitro formation of thiamin triphosphate (TTP) from thiamin diphosphate (TDP) and ADP in addition to ATP formation from ADP [Shikata, H. et al. (1989) Biochem. Int. 18, 933-942]. To obtain evidence for in vivo synthesis of TTP by AK1, changes in TTP content and AK1 activity were determined in chicken skeletal muscle during development after hatching. Thiamin phosphate metabolism in chicken skeletal muscle was also studied. i) An extremely high TTP content, 81% of total thiamin (thiamin plus thiamin phosphates), was detected in the white (fast-twitch) muscle of adult normal chicken (5th to 9th month) compared with a relatively high TTP content of 31% in the red (slow-tonic) muscle. Since approximately equivalent amounts of total thiamin were present in the two types of muscle, the ratio of TTP to TDP was high (5.0) in the white muscle and low (0.41) in the red muscle. ii) Rabbit anti-chicken AK1 antiserum against the purified chicken cytosolic AK1 preparation was obtained. Both AK1 activity and TTP-synthesizing activity in crude cytosol fraction of adult chicken white muscle were inhibited in parallel by the antiserum. iii) In the white muscle of normal chicken, the TTP content and AK1 activity responsible for forming either ATP or TTP were increased in a parallel manner up to day 16 after hatching, after which both remained constant. In the red muscle, on the other hand, both the TTP content and the AK1 activity were low in comparison with those in the white muscle, and were almost constant after hatching.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229027 TI - Phosphorylated and dephosphorylated types of non-activated glucocorticoid receptor. AB - We purified glucocorticoid receptors quickly but very partially using DEAE-resin. [3H]-Triamcinolone acetonide-labeled and non-activated receptors in the quickly purified fraction were found to be separated into two fractions (P-2 and P-3) by hydroxyapatite column chromatography. The P-2 receptor was the main component, and the ratio of P-2/P-3 was around 2. The molecular weights of the two receptors were calculated to be the same, 242,000: Rs = 6.2 nm and s20,w = 9.0. Treatment of the receptor with catalytic subunits of phosphoprotein phosphatase 2A1 reduced the P-2/P-3 ratio from 2 to 0.5, while treatment with catalytic subunits of cAMP dependent protein kinase and ATP increased it to 2.5. The isolated P-3 receptor could be converted into the P-2 type by the kinase treatment. Tungstate, a phosphatase inhibitor, stabilized the P-2 receptor, and the P-2/P-3 ratio was larger than 3 when the DEAE-fraction was prepared in the presence of tungstate. However, the tungstate effect was not very strong, and the P-2 type tended to change into the P-3. [3H]-Triamcinolone acetonide-labeled and non-activated receptors were purified very highly by using an affinity gel; the procedure required more than 10 h. Only the P-3 form was observed in the preparation of highly purified receptors. Hormone-free receptors were affected by neither the phosphatase nor the kinase. The results indicate that the hormone binding makes the receptor sensitive to phosphatase. The reversibly dephosphorylated receptor is more stable than the non-dephosphorylated one, and can be activated. PMID- 2229028 TI - A heparin binding protein whose expression increases during differentiation of embryonal carcinoma cells to parietal endoderm cells: cDNA cloning and sequence analysis. AB - A cDNA clone isolated from a lambda gt11 expression library of teratocarcinoma OTT6050 specifies for a glycoprotein with a molecular weight of about 44,000. The new glycoprotein was termed heparin binding protein-44 (HBP-44), since it was absorbed to a heparin-agarose column and was eluted from it by a buffer containing 1.5 M NaCl. HBP-44 mRNA was intensely expressed in PYS-2 parietal endoderm cells and in the kidney, and the RNA level increased about 10-fold during differentiation of F9 embryonal carcinoma cells to parietal endoderm cells. From the cDNA sequence, HBP-44 was concluded to be rich in charged amino acids, and large segments of the protein appeared to form alpha-helixes. The protein was considered to be anchored to the membrane by a cluster of hydrophobic amino acids present in the N-terminal region. Indeed, the N-terminal sequence of HBP-44 was homologous to asialoglycoprotein receptor, which is anchored to the membrane by the N-terminal region. Furthermore, a portion of the N-terminal region of HBP-44 was homologous to the leucine zipper domain. Except for the N terminal region, HBP-44 had over-all homology with structural proteins such as myosin heavy chain. We propose that HBP-44 is extruded from plasma membranes and interacts with heparin and related molecules and that it is involved in the interactions of plasma membranes with basement membranes. PMID- 2229029 TI - Primary structure of a base non-specific and adenylic acid preferential ribonuclease from Aspergillus saitoi. AB - The complete primary structure of a base non-specific and adenylic acid preferential RNase (RNase M) from Aspergillus saitoi was determined. The sequence was determined by analysis of the peptides generated by digestion of heat denatured RNase M with lysylendopeptidase, and the peptides generated from RCM RNase M by digestion with staphylococcal V8 protease or chemical cleavage with BrCN. It consisted of 238 amino acid residues and carbohydrate moiety attached to the 74th asparagine residue. The molecular weight of the protein moiety deduced from the sequence was 26,596. The locations of 10 half cystine residues are almost superimposable on those of RNase Rh from Rhizopus niveus and RNase T2 from Aspergillus oryzae which have similar base specificity. The homology between RNase M and RNase Rh and RNase T2 amounted to 97 and 160 amino acid residues, respectively. The amino acid sequences conserved in the three RNases are concentrated around the three histidine residues, which are supposed to form part of the active sites of these RNases. PMID- 2229030 TI - Repression of serotonin secretion by an endogenous Ca2(+)-activated protease in electropermeabilized bovine platelets. AB - Micromolar levels of free calcium ions added to the extracellular medium elicit secretion of serotonin from electropermeabilized bovine platelets in the presence of millimolar levels of Mg-ATP. Such Ca2(+)-dependent secretion of serotonin was almost completely impaired when the permeabilized platelets were preincubated for 1 min at 35 degrees C in 100 microM Ca2+ without Mg-ATP. The half-maximal effect was observed with about 45 microM Ca2+ in the preincubation medium. Inhibitors of serine-thiol protease, such as leupeptin and antipain, suppressed the impairment of the secretion of serotonin by the preincubation with Ca2+. Electron microscopic observation revealed that disorganization of the cytoskeletal structures, in particular of the membrane undercoat and the network of microfilaments, accompanied the impairment of secretion of serotonin. Microfilaments were also found to be dissociated from dense granules that contained serotonin. These morphological changes were also suppressed when antipain was included in the Ca2(+)-preincubation medium. Coincident with these morphological changes, the following biochemical changes were observed in 100 microM Ca2+ but not in the presence of Ca2+ and antipain. The amount of Triton insoluble cytoskeleton and the acto-myosin content of the dense-granule fraction were markedly decreased. The decrease in Triton-insoluble cytoskeletons was quantitatively correlated with the degree of impairment of secretion of serotonin. Immunoblot analysis of EGTA extracts of the cells showed that the 240 kDa spectrin in platelets was degraded to a 235-kDa fragment, and a 260-kDa actin binding protein (ABP) in platelets was partially degraded to 190- and 110-kDa components.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229031 TI - UDP-glucose pyrophosphorylase from potato tuber: cDNA cloning and sequencing. AB - We have isolated a cDNA encoding UDP-glucose pyrophosphorylase from a cDNA library of immature potato tuber using oligonucleotide probes synthesized on the basis of partial amino acid sequences of the enzyme. The cDNA clone contained a 1,758-base-pair insert including the complete message for UDP-glucose pyrophosphorylase with 1,431 base pairs. The amino acid sequence of the enzyme inferred from the nucleotide sequence consists of 477 amino acid residues. All the partial amino acid sequences determined protein-chemically [Nakano et al. (1989) J. Biochem. 106, 528-532] confirmed the primary structure of the enzyme. An N-terminal-blocked peptide was isolated from the proteolytic digest of the enzyme protein, and the blocking group was deduced to be an acetyl group by fast atom bombardment-mass spectrometry. On the basis of the predicted amino acid sequence (477 residues minus the N-terminal Met plus an acetyl group), the molecular weight of the enzyme monomer is calculated to be 51,783, which agrees well with the value determined by polyacrylamide gel electrophoresis. In the cDNA structure, the open-reading frame is preceded by a 125-base-pair noncoding region, which contains a sequence being homologous with the consensus sequence for plant genes, and is followed by a 174-base-pair noncoding sequence including a polyadenylation signal. Amino acid sequence comparisons revealed that the potato UDP-glucose pyrophosphorylase is homologous to the enzyme from slime mold, Dictyostelium discoideum, but not to ADP-glucose pyrophosphorylases from rice seed and Escherichia coli. PMID- 2229032 TI - Purification and properties of 4-hydroxy-4-methyl-2-oxoglutarate aldolase from Pseudomonas ochraceae grown on phthalate. AB - 4-Hydroxy-4-methyl-2-oxoglutarate aldolase [4-hydroxy-4-methyl-2-oxoglutarate pyruvate-lyase: EC 4.1.3.17] has been purified to homogeneity (about 770-fold purification, yield 11.4%) from Pseudomonas ochraceae grown on phthalate. The enzyme has a molecular weight of 160,000 (gel filtration on Bio-Gel A-1.5m), a subunit molecular weight of 26,000 (SDS-PAGE) and an isoelectric point of 5.0 (isoelectric focusing). The enzyme requires divalent metal ions such as Mg2+, Mn2+, Co2+, Zn2+, and Cd2+ for activity. The enzyme actively cleaves 4-carboxy-4 hydroxy-2-oxoadipate, a physiological substrate of the enzyme, to give pyruvate and oxaloacetate, but shows much lower affinity for 4-hydroxy-4-methyl-2 oxoglutarate. 4-Hydroxy-2-oxoglutarate is cleaved at a low rate to pyruvate and glyoxylate. The l-isomers of the substrates are preferentially cleaved rather than the d-isomers as determined polarimetrically. The enzyme reactions are reversible: the equilibrium constants (pH 8.0, 25 C) for the HMG and HG cleavage reactions are about 0.07 and 0.03 M, respectively, whereas no equilibrium is observed with CHA due to oxaloacetate beta-decarboxylase activity associated with the enzyme. The enzyme activity is hardly affected by thiols and thiol reagents. The non-enzymatic cleavage reaction caused by various metal ions has also been studied to examine the mechanistic similarity to the enzymatic reaction. PMID- 2229033 TI - Activation of Pseudomonas ochraceae 4-hydroxy-4-methyl-2-oxoglutarate aldolase by inorganic phosphate. AB - Pseudomonas ochraceae 4-hydroxy-4-methyl-2-oxoglutarate aldolase [4-hydroxy-4 methyl-2-oxoglutarate pyruvate-lyase: EC 4.1.3.17], one of the metal ion requiring aldolases, is markedly activated by Pi. The activation is reversible and can be observed in every step of enzyme purification. The extent of activation is almost independent of the metal ion used, but varies with each substrate. The cleavage of l-4-carboxy-4-hydroxy-2-oxoadipate, a physiological substrate of the enzyme, is most strongly activated: Pi gives a hyperbolic activation curve with an activation constant of 0.36 mM and a maximum activation of about 65-fold. Arsenate, phosphorous acid, bicarbonate, acetyl phosphate, thiamine diphosphate, ADP, PPi, and ATP are also effective to various extents. These anions appear to be effective in the free form but not in the metal ion complex. Many organic and inorganic anions are ineffective. Pi causes parallel increases in Vmax and in Km for substrate or metal ion with a concomitant shift of the optimum pH toward the alkaline side, and the enhancement of activity is closely correlated with the shift of optimum pH. Pi induces no gross change of molecular form of the enzyme protein as evaluated from gel filtration, PAGE, UV, fluorescence, and CD spectral data. Based on these findings, the mechanism and the physiological meaning of the observed activation are discussed. PMID- 2229035 TI - Anion exchange reactions in bacteria. AB - Bacterial anion exchange now includes both "carboxylate-linked" reactions in which there is an antiport of mono- and dicarboxylic acids, and "Pi-linked" reactions that build on phosphate (Pi) and organic phosphates. To illustrate the general features of this expanding class, this article discussed the biochemistry, physiology, and molecular biology of Pi-linked antiporters that accept glucose 6-phosphate (G6P) as their primary substrate. Kinetic and biochemical analysis suggests that Pi-linked exchangers have a bifunctional active site that accepts a pair of negative charges. For this reason, exchange stoichiometry moves between the limits of 2:1 and 2:2 to reflect the ratio of mono- and divalent substrates at either membrane surface. This results in a particularly interesting reaction sequence in vivo, where, because cytosolic pH is relatively alkaline, one can expect the asymmetric exchange of two monovalent G6P anions against a single divalent G6P. In this way, an otherwise futile self exchange of G6P gives a net flux driven (indirectly) by the pH gradient. Despite this biochemical and physiological complexity, Pi-linked carriers resemble all other secondary carriers at a molecular level. Indeed, sequence analysis leads one to infer a common (albeit low resolution) structural theme in which each functional unit has two sets of six trans-membrane alpha helices separated by a central hydrophilic loop. Present examples show that this topology can derive from either a single protein, as is typical in bacteria, or from pairs of identical subunits, as found in mitochondria and chloroplasts. The finding of this common structure should make it possible to build detailed structural models that have implications for all membrane carrier proteins. PMID- 2229034 TI - Transport systems encoded by bacterial plasmids. AB - A variety of bacterial functions are encoded on plasmids, extrachromosomal elements. Examples of plasmid-borne functions are antibiotic production and resistance, degradation of recalcitrant chemicals, virulence factors, and plant symbiotic properties. Several transport systems with diverse functions have recently been found to be carried on plasmids. These systems serve to either accumulate or extrude a compound from a cell. The focus of this review is to present a survey on several of these novel plasmid-borne transport systems emphasizing functions, components, and molecular genetics. PMID- 2229037 TI - Bifunctional role of glycosphingolipids. Modulators for transmembrane signaling and mediators for cellular interactions. AB - Glycosphingolipids (GSLs), or their modified catabolites, at the cell surface modulate transmembrane signal transduction by influencing protein kinases associated with growth factor receptors and protein kinase C. On the other hand, the same or different GSLs at the cell surface interact in highly specific fashion with other GSLs or with binding proteins, possibly at the surface of adjacent interacting cells or in the extracellular matrix. The GSL-GSL interaction apparently provides the basis for a specific cell recognition system independent of the fibronectin/integrin or surface lectin systems, occurring earlier during a cell recognition event. PMID- 2229038 TI - Mutations in fnr that alter anaerobic regulation of electron transport-associated genes in Escherichia coli. AB - The fnr gene product, FNR, is a global regulator of anaerobic gene expression in Escherichia coli. When E. coli is switched from aerobic to anaerobic growth conditions, cytochrome o (cyoABCDE) and d oxidase (cydAB) genes are repressed and the anaerobic terminal reductase genes, including nitrate (narGHJI), dimethyl sulfoxide/trimethylamine (dmsABC), and fumarate (frdABCD) reductase, are induced. To determine if certain amino acid residues are essential for FNR to function in this regulatory process, site-directed mutations were introduced into the fnr gene. The resulting mutant proteins were assayed in vivo for their ability to either activate dmsA'-'lacZ and frdA'-'lacZ gene expression, or repress expression of a cyoA'-'lacZ gene fusion. The fnr mutants were grouped into four classes. Class I exhibited a severe decrease in the ability to either activate or repress fnr-dependent gene expression. Mutations in four of the five cysteine residues in the FNR protein were in this class. The sole exception was an FNR Cys16----Ser "mutant" that exhibited normal activity. Class II mutations caused a mild reduction in FNR-dependent activation or repression while Class III mutations conferred a modest increase in the ability of the FNR protein to activate gene expression under aerobic conditions (i.e. FNR*). Finally, Class IV mutations lowered the modest aerobic FNR transcriptional activation function proportionally more than the anaerobic FNR activity. These findings identify an essential role for the NH2 terminus of the FNR protein in its various activities in anaerobic gene regulation. PMID- 2229036 TI - Binding protein-dependent transport systems. AB - Bacterial binding protein-dependent transport systems are the best characterized members of a superfamily of transporters which are structurally, functionally, and evolutionary related to each other. These transporters are not only found in bacteria but also in yeasts, plants, and animals including man, and include both import and export systems. Although any single system is relatively specific, different systems handle very different substrates which can be inorganic ions, amino acids, sugars, large polysaccharides, or even proteins. Some are of considerable medical importance, including Mdr, the protein responsible for multidrug resistance in human tumors, and the product of the cystic fibrosis locus. In this article we review the current state of knowledge on the structure and function of the protein components of these transporters, the mechanism by which transport is mediated, and the role of ATP in the transport process. PMID- 2229039 TI - Amino acid sequence and characterization of a heparin-binding neurite-promoting factor (p18) from bovine brain. AB - A neurite-promoting factor (p18) was isolated from bovine brain using ammonium sulfate fractionation, sulfated Sephadex G-50 chromatography, heparin-Sepharose gel chromatography, and reverse phase high performance liquid chromatography. The complete amino acid sequence of p18 was determined by automated Edman degradation of S-pyridylethylated p18, and its peptide fragments produced by cyanogen bromide cleavage and by digestion with specific endoproteinases. Alignment of the amino acid sequences of these peptides revealed that p18 consists of 119 amino acid residues with a calculated molecular weight of 14,200. p18 appears to possess five disulfide bonds per molecule. A region of amino acid sequence at the C terminus of p18 shows a structural feature homologous to that around the reactive sites of Kazal-type protease inhibitors. However, p18 did not exhibit anti trypsin activity. p18 showed very little, if any, mitogenic activity toward NIH 3T3 cells and Swiss mouse 3T3 cells. p18 was found to bind to a specific receptor with an apparent Kd of approximately 8 nM and receptor numbers 1.7 x 10(5) and 1.0 x 10(4) for NIH 3T3 cells and PC12 cells (rat pheochromocytoma cells), respectively. PMID- 2229040 TI - Saturation site-directed mutagenesis of thymidylate synthase. AB - We have subjected 12 different codons of a synthetic Lactobacillus casei thymidylate synthase (TS) gene to saturation site-directed mutagenesis to create amino acid "replacement sets" at each of those positions. The target residues were chosen because they are highly conserved and because they are important for the structure and function of the protein as indicated by solution and structural studies. The mutagenesis procedure involved excision of a fragment of the synthetic gene containing the target codon, followed by its replacement with a mixture of oligonucleotides which code for all 20 amino acids and the amber stop codon. TS mutants were identified by DNA sequencing, and catalytically active mutants were identified by genetic complementation using a Thy- strain of Escherichia coli. Only 3 of the 12 target amino acids examined were essential for TS activity; and of the 125 total mutants identified, 57 were catalytically active. These results point to a high degree of plasticity of TS in accommodating function with structural change. PMID- 2229041 TI - Cleavage of disulfide bonds in endocytosed macromolecules. A processing not associated with lysosomes or endosomes. AB - Whereas there is biological evidence that the reductive cleavage of disulfide bonds is critical for the activation of endocytosed macromolecules such as toxins, immunotoxins, and other drug carriers, virtually nothing is known about the specifics of this cleavage. To study this process, a model compound was synthesized in which a radioiodinated tyramine was linked through a disulfide bond to an undegradable carrier, poly(D-lysine), known to be efficiently endocytosed. Cultured Chinese hamster ovary cells were pulse-labeled with this probe, and the disulfide cleavage was measured as released acid-soluble radioactivity at different times of chase. Pulse-labeled cells were also subjected to subcellular fractionation to identify intracellular structures associated with disulfide cleavage. Cleavage began without lag, amounted to about approximately 7% of the initial cell-bound radioactivity in the first hour and continued for more than 6 h. It was abolished in the presence of N ethylmaleimide. When sulfhydryl groups present at the cell surface were blocked with cell-impermeant sulfhydryl reagent, the initial phase of disulfide cleavage was inhibited, indicating that cleavage began at the cell surface. A long-lasting intracellular phase of disulfide cleavage began after about approximately 30 min of chase. Subcellular fractionation and kinetic analysis indicated that neither lysosomes nor endosomes were participating in that phase, leaving the Golgi apparatus as the most probable site of endocytic disulfide cleavage. PMID- 2229042 TI - Transmission of ADP.vanadate-induced conformational changes to three peptide segments of myosin subfragment-1. AB - In order to study the conformational changes associated with formation of the stable ternary complex of myosin subfragment-1 (S-1) with ADP and orthovanadate (Vi), S-1 was fluorescently labeled with 9-anthroylnitrile, 4-fluoro-7-nitrobenz 2-oxa-1,3-diazole, and 5-(iodoacetamido) fluorescein at the 23-, 50-, and 20-kDa peptide segments of S-1, respectively (Hiratsuka, T. (1989) J. Biol. Chem. 264, 18188-18194; Hiratsuka, T. (1986) J. Biol. Chem. 261, 7294-7299; Takashi, R. (1979) Biochemistry 18, 5164-5169). The extrinsic fluorescence of these S-1 derivatives was sensitive not only to binding of ADP but to formation of the stable ternary complex with ADP and Vi. By using these fluorescent properties, the kinetics of formation of the stable ternary complexes of these S-1 derivatives with ADP and Vi, M. ADP.Vi, were analyzed according to the scheme proposed by Goodno (Goodno, C. C. (1979) Proc. Natl. Acad. Sci. U. S. A. 76, 2620 2624). [Formula; see text] The values obtained for KVi )0.2-0.4 mM) and k (0.03 0.05 s-1) of these S-1 derivatives were similar regardless of the peptide segments of S-1 where the fluorophore had been covalently labeled. These results suggest that the conformational changes, which are induced by formation of the stable ternary complex of S-1 with ADP and Vi, are transmitted to all three peptide segments of S-1 at a similar rate. The present results also encourage us to confirm that the ATPase site of S-1 resides at or near the region where all three peptide segments of S-1 are contiguous. PMID- 2229043 TI - Kinetics of conformational changes in Nereis sarcoplasmic calcium-binding protein upon binding of divalent ions. AB - The sarcoplasmic calcium-binding protein (SCP) of the sandworm Nereis possesses three Ca2(+)-Mg2+ sites but no Ca2(+)-specific site. Binding of Mg2+, but not of Ca2+, displays a marked positive cooperativity. The apparent cooperativity of Ca2+ binding in the presence of Mg2+ results from the allostery in Mg2+ dissociation. Binding of the first Ca2+ or Mg2+ induces all the conformational change, monitored by Trp fluorescence. In displacement reactions the conformational changes occur in the step SCP.Mg3----SCP.Ca1Mg2. Stopped-flow experiments indicate that Trp fluorescence changes upon Ca2(+)-binding are instantaneous whereas Mg2(+)-binding involves a fast pre-equilibrium (Keq = 28 M 1), followed by two slow consecutive conformational changes with k1 = 13.5 s-1 and k2 = 0.21 s-1. The fluorescence change after dissociation of Ca2+ from SCP is monophasic with k = 0.02 s-1; that after Mg2+ dissociation is biphasic with k1 = 0.8 s-1 and k2 = 0.1 s-1. Trp life time measurements also indicate that Ca2(+)- and Mg2(+)-induced conformational changes are completely different. Displacement of bound Ca2+ by Mg2+ can be described by two consecutive reactions in which the first (without fluorescence change) corresponds to the dissociation of the last Ca2+ (k1 = 2.4 s-1) and the second (k2 = 0.45 s-1) to the final conformational change observed upon direct Mg2+ binding. Displacement of bound Mg2+ by Ca2+ follows the kinetic scheme of simple competition; the conformational rate constant approaches asymptotically (up to the limit of 129 s-1) the dissociation rate of Mg2+ as the concentration of Ca2+ increases. In summary, after fast dissociation of Ca2+ or Mg2+, Nereis SCP slowly converts to the metal-free configuration, but in Ca2(+)-Mg2+ exchange reactions, the conformational changes are nearly as fast as the cation dissociation reactions. PMID- 2229044 TI - Thermodynamic study of protein dynamic structure in the oxygen binding reaction of myoglobin. AB - We examined the flash photolysis of oxy complexes of sperm whale myoglobin (Mb) on the nanosecond time scale at ambient temperatures. In this time range, we can observe the geminate reaction of Mb with the O2 ligand existing in the protein matrix after the photodissociation from the heme iron. We found that the fraction of the geminate component to the total O2 photodissociation exhibited temperature dependences. The geminate fraction decreased with rising temperature, indicating that the protein fluctuation is enhanced at high temperature because of thermal agitation. However, the temperature-dependent behavior showed a break at 20 degrees C. Concerning the geminate O2 escaping reaction from the protein matrix to the solvent region, the activation energy above 20 degrees C (0.4 +/- 0.4 kcal/mol) is significantly lower than that below 20 degrees C (5.1 +/- 0.4 kcal/mol). Thermodynamic analysis on the basis of the transition state theory indicated that the O2 escaping reaction above 20 degrees C is entropy dominated whereas that below 20 degrees C is enthalpy dominated. The results were qualitatively compatible with the theoretical prediction by J. Kottalam and D. A. Case [1988) J. Am. Chem. Soc. 110, 7690-7697). Comparing the kinetic and thermodynamic process of the O2 geminate reaction among several Mbs, we concluded that the geminate O2 reaction with Mb is governed by the dynamic motion of the protein which is sensitively controlled by the static interaction of the heme moiety with the surroundings. PMID- 2229045 TI - The proton motive force lowers the level of ATP required for the in vitro translocation of a secretory protein in Escherichia coli. AB - The role of the electrochemical potential difference of proton (delta mu H+) in protein translocation across the membrane of Escherichia coli was examined in detail using an efficient in vitro assay system (Yamada, H., Tokuda, H., and Mizushima, S. (1989) J. Biol. Chem. 264, 1723-1728). Delta mu H+ reduced the level of ATP necessary for the efficient translocation of OmpF-Lpp, a chimeric model secretory protein. The apparent Km value of the translocation reaction for ATP was lower by 2 orders of magnitude in the presence of delta mu H+ than in its absence. The membrane potential and delta pH, both of which are components of delta mu H+, independently lowered the apparent Km value of the translocation reaction for ATP. An ATP-generating system also lowered the level of ATP required for translocation in the absence of delta mu H+ but not in its presence. It is proposed that ADP formed during protein translocation lowers the affinity of the putative translocation machinery for ATP and that the removal of ADP from the secretory machinery, a possible critical step in the translocation reaction, is stimulated in the presence of either delta mu H+, an ATP-generating system, or a higher concentration of ATP. PMID- 2229046 TI - Caldesmon-binding sites on tropomyosin. AB - The interaction of chicken gizzard caldesmon with fragments of tropomyosin, generated by chemical, enzymatic, and mutational means, was studied to determine the caldesmon-binding site(s) on tropomyosin. Binding was examined by fluorescence spectroscopy and affinity chromatography. Removal of residues 1-141 and 228-284, respectively, from the NH2 and COOH ends of tropomyosin did not affect its binding to caldesmon significantly, indicating that the major, caldesmon-binding region lies between residues 142-227. The Escherichia coli produced chicken gizzard beta-tropomyosin mutant, CSM-beta (1/8/12-227), bound caldesmon about 2-fold stronger than a similar mutant of residues 8-200. This further focused the primary caldesmon-binding site to residues 201-227. Cleavage of tropomyosin at CYS-190 weakened markedly the binding of the two resulting fragments, residues 1-189 and 190-284, to caldesmon suggesting the requirement for the integrity of the caldesmon-binding region between residues 142227 of tropomyosin for strong interaction with caldesmon. Based on data from this study and others, we have proposed models for the interaction of tropomyosin with caldesmon in vitro, as well as the possible arrangement of the smooth muscle thin filament proteins in vivo. PMID- 2229047 TI - Relationship of cholesterol content to spatial distribution and age of disc membranes in retinal rod outer segments. AB - The initial events of visual transduction occur on disc membranes which are sequestered within the photoreceptor outer segment. In rod cells, the discs are stacked in the outer segment. Discs are formed at the base of the rod outer segment (ROS) from evaginations of the plasma membrane. As new discs form, older discs move toward the apical tip of the rod, from which they are eventually shed and subsequently phagocytosed by the adjacent pigment epithelium. Thus, disc membranes within a given rod cell are not of uniform age. We have recently shown that disc membranes are not homogeneous with respect to cholesterol content (Boesze-Battaglia, K., Hennessey, T., and Albert, A. D. (1989) J. Biol. Chem. 264, 8151-8155). In the present study, freshly isolated bovine retinas were incubated with [3H]leucine for 4 h in order to allow sufficient time for the radiolabeled proteins to become incorporated into the basal-most (newest) discs. Osmotically intact discs were then isolated. After the addition of digitonin, the discs were fractionated based on cholesterol content, and radioactivity (indicative of newly synthesized protein) was measured. Discs which exhibited high cholesterol content also exhibited high radio-activity. These results demonstrate that the cholesterol heterogeneity of ROS disc membranes is related to the age, and thus the position, of the discs in the ROS. PMID- 2229048 TI - Amino acid sequences of two proline-rich bactenecins. Antimicrobial peptides of bovine neutrophils. AB - Bactenecins are highly cationic polypeptides of the large granules of bovine neutrophils, exerting in vitro a potent antimicrobial activity. Two bactenecins, with an approximate molecular weight of 7000 and 5000, called Bac7 and Bac5, are characterized by a high content of proline (greater than 45%) and arginine (greater than 23%) residues. Their complete amino acid sequences were determined by automated Edman degradation combined, in the case of Bac5, with plasma desorption mass spectrometry. Bac7 comprises 59 residues and includes three tandem repeats of a tetradecamer characterized by several Pro-Arg-Pro triplets spaced by single hydrophobic amino acids. Resolution of the primary structure of Bac5 required fragmentation with N-bromosuccinimide as well as digestion of the obtained C-terminal fragment with carboxypeptidases P and Y directly in the mass spectrometer. Bac5 comprises 42 amino acid residues with a repeated motif of Arg Pro-Pro triplets also alternating with single apolar residues. PMID- 2229049 TI - Glucose regulation of insulin receptor affinity in primary cultured adipocytes. AB - Treatment of primary cultured adipocytes with 20 mM glucose resulted in a progressive increase in specific 125I-insulin binding that began almost immediately (no lag period) and culminated in a 60% increase by 24 h. This effect was dose-dependent (glucose ED50 of 4.6 mM) and mediated by an increase in insulin receptor affinity. Moreover, it appears that glucose modulates insulin receptor affinity through de novo protein synthesis rather than through covalent modification of receptors, since cycloheximide selectively inhibited the glucose induced increase in insulin binding capacity (ED50 of 360 ng/ml) and restored receptor affinity to control values. Importantly, insulin sensitivity of the glucose transport system was increased by glucose treatment (63%) to an extent comparable with the enhancement in receptor affinity, thus indicating a functional coupling between insulin binding and insulin action. When the long term effects of insulin were assessed (24 h), we found that insulin treatment reduced 125I-insulin binding by greater than 60% by down-regulating the number of cell surface receptors in a dose-dependent manner (insulin ED50 of 7.4 ng/ml). On the basis of these studies, we conclude that 1) insulin binding is subject to dual regulation (glucose controls insulin action by enhancing receptor affinity, whereas insulin controls the number of cell surface receptors); and 2) glucose appears to modulate insulin receptor affinity through the rapid biosynthesis of an affinity regulatory protein. PMID- 2229050 TI - Growth inhibition by vaccinia virus growth factor. AB - Vaccinia virus growth factor (VGF), a highly glycosylated 77-residue epidermal growth factor (EGF)-like polypeptide encoded in vaccinia poxvirus, is reported to play an important role in stimulating growth of uninfected cells to facilitate virus infection. We have chemically synthesized the unglycosylated forms of VGF and VGF19-69, a shortened VGF analog consisting of 51 residues and comprising the EGF-homologous region (position 19-69) of VGF. Both synthetic forms of VGFs were purified to homogeneity and vigorously characterized by various criteria, including the Cf-252 ion fission fragment mass spectrometry, amino acid sequencing, and enzymatic digestion to confirm the disulfide linkages. Synthetic VGFs exhibited high affinity binding to the EGF receptors in A431, NRK 49F, NRK clone 3, and NIH 3T3 cells, but, unlike the glycosylated form, showed contrasting mitogenic activities in various cells in vitro. Synthetic VGFs showed low levels of mitogenic and colonogenic activities in NRK clone 49F cells and NIH 3T3 cells, full agonist activities in human keratinocytes and Swiss 3T3 cells, and partial agonist activities in NRK clone 3 cells. Our results suggest that the unglycosylated form of VGF is an EGF antagonist to selected cells and that the production of unglycosylated form of VGF by the cytolytic vaccinia virus may serve as a mechanism whereby inhibition of growth and metabolism of selected host cells may be used to facilitate the propagation of the virus infection. PMID- 2229051 TI - Stoichiometry, base orientation, and nuclease accessibility of RecA.DNA complexes seen by polarized light in flow-oriented solution. Implications for the mechanism of genetic recombination. AB - By using flow linear dichroism, in combination with nuclease digestion and two spectroscopically distinguishable DNAs, we demonstrate the existence of two internal and one external DNA-binding sites in the RecA fiber. A number of different complexes between RecA and single- and double-stranded DNAs are characterized with respect to stoichiometry, location, and base orientation of each of the associated DNAs. Based on these results, we discuss important steps of the mechanism of general genetic recombination. PMID- 2229052 TI - Transient spectroscopy of the reaction of cyanide with ferrous myoglobin. Effect of distal side residues. AB - The reaction of cyanide metmyoglobin with dithionite conforms to a two-step sequential mechanism with formation of an unstable intermediate, identified as cyanide bound ferrous myoglobin. This reaction was investigated by stopped-flow time resolved spectroscopy using different myoglobins, i.e. those from horse heart, Aplysia limacina buccal muscle, and three recombinant derivatives of sperm whale skeletal muscle myoglobin (Mb) (the wild type and two mutants). The myoglobins from horse and sperm whale (wild type) have in the distal position (E7) a histidyl residue, which is missing in A. limacina Mb as well as the two sperm whale mutants (E7 His----Gly and E7 His----Val). All these proteins in the reduced form display an extremely low affinity for cyanide at pH less than 10. The differences in spectroscopy and kinetics of the ferrous cyanide complex of these myoglobins indicate a role of the distal pocket on the properties of the complex. The two mutants of sperm whale Mb are characterized by a rate constant for the decay of the unstable intermediate much faster than that of the wild type, at all pH values explored. Therefore, we envisage a specific role of the distal His (E7) in controlling the rate of cyanide dissociation and also find that this effect depends on the protonation of a single ionizable group, with pK = 7.2, attributed to the E7 imidazole ring. The results on A. limacina Mb, which displays the slowest rate of cyanide dissociation, suggests that a considerable stabilizing effect can be exerted by Arg E10 which, according to Bolognesi et al. (Bolognesi, M., Coda, A., Frigerio, F., Gatti, C., Ascenzi, P., and Brunori, M. (1990) J. Mol. Biol. 213, 621-625), interacts inside the pocket with fluoride bound to the ferric heme iron. A mechanism of control for the rate of dissociation of cyanide from ferrous myoglobin, involving protonation of the bound anion, is discussed. PMID- 2229053 TI - Refolding of an integral membrane protein. OmpA of Escherichia coli. AB - OmpA is an integral membrane protein from the outer membrane of Escherichia coli. Purified, lipopolysaccharide-free OmpA was denatured by boiling in sodium dodecyl sulfate (SDS). Refolding was then induced by replacement of SDS with the nonionic detergent octylglucoside. The structure of both the denatured and refolded protein were investigated by SDS-gel electrophoresis, protease digestion, Raman and fluorescence spectroscopy. Refolded OmpA could be reconstituted into membranes of the synthetic lipid dimyristoylphosphatidylcholine. Thus, lipopolysaccharide is neither necessary for proper folding of OmpA nor for its insertion into lipid membranes. Based on this result, models for sorting of OmpA into the outer membrane of E. coli are discussed. PMID- 2229054 TI - Displacement of rhodopsin by GDP from three-loop interaction with transducin depends critically on the diphosphate beta-position. AB - We have studied the effect of GDP and its analog guanyl-5'-yl thiophosphate (GDP beta S) on the interaction between rhodopsin and transducin (Gt). Stabilization of the light-induced active intermediate, metarhodopsin II (MII), by bound Gt (extra-MII effect) monitored the catalytic interaction between the proteins. Extra-MII can be completely abolished by GDP, with a half-suppression at 10 microM under the conditions (4 degrees C, pH 8, 7.5 nM photoactivated rhodopsin). The effect of GDP did not depend on divalent cations, in contrast to GTP-induced dissociation of the complex. The GDP analog GDP beta S did not affect extra-MII although it binds to the MII-Gt complex with only three times lower affinity (reversal of the GDP effect by GDP beta S). However, GDP beta S enhanced considerably the efficiency of synthetic rhodopsin peptide competition against the formation of extra-MII. GDP and GDP beta S slow the Gt activation rate (monitored by kinetic light scattering), with the same relative efficiencies. We therefore assume that GDP, GDP beta S, and GTP bind at the same site. We discuss a generalized induced fit mechanism, where MII induces opening of the Gt nucleotide site and release of GDP which in turn is obligatory to establish the MII-stabilizing rhodopsin-Gt three-loop interaction (Konig, B., Arendt, A., McDowell, J.H., Kahlert, M., Hargrave, P.A., and Hofmann, K.P. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6878-6882). The GDP beta S/GDP difference is discussed in terms of bound GDP disturbing the interaction with two and GDP beta S with only one of the rhodopsin binding sites. Mechanistically, our results indicate a critical role of the beta-phosphate interaction with the nucleotide binding site in the GDP-induced transformation of Gt. PMID- 2229055 TI - Evidence for direct interaction between cysteine 138 and the flavin in thioredoxin reductase. A study using flavin analogs. AB - The flavoenzyme thioredoxin reductase from Escherichia coli contains an oxidation reduction active disulfide made up of Cys135 and Cys138. Mutations changing each Cys residue to a Ser residue have been effected (Prongay, A. J., engelke, D. R., and Williams, C. H., Jr. (1989) J. Biol. Chem. 264, 2656-2664). The FAD prosthetic group of each altered thioredoxin reductase has been replaced with 1 deaza-FAD (a flavin analog with carbon substituted for nitrogen at position 1), 4 thio-FAD (a flavin analog with sulfur substituted for oxygen at position 4), and 6-thiocyanato-FAD. 1-Deaza-FAD-TRR(Cys135,Ser138) has absorbance and fluorescence spectral properties similar to the oxidized form of wild type apothioredoxin reductase reconstituted with 1-deaza-FAD. The absorbance spectrum of 1-deaza-FAD TRR(Ser135,Cys138) is similar to the spectrum of the two-electron reduced form of wild type apothioredoxin reductase reconstituted with 1-deaza-FAD, indicating that it is a mixture of two species (O'Donnell, M. E., and Williams, C. H., Jr. (1984) J. Biol. Chem. 259, 2243-2251). The spectrum of one of these species of 1 deaza-FAD-TRR(Ser135,Cys138) resembles the spectrum of oxidized 1-deaza-FAD bound to wild type apothioredoxin reductase. The other species has an absorbance spectrum with a single peak at 400 nm (epsilon 400 = 11,100 M-1 cm-1) and resembles the spectrum of a thiolate adduct at the C4a position of the 1-deaza FAD. The equilibrium between these species is pH-dependent, with a maximum of 50% C4a-adduct formation at low pH, and is linked to pK alpha values at 8.2 and 9.3. The absorbance spectrum of 4-thio-FAD-TRR(Cys135,Ser138) resembles the spectrum of the unbound 4-thio-FAD, whereas 4-thio-FAD-TRR(Ser135,Cys138) has a spectrum indicative of a mixture of 4-thio-FAD and FAD, suggesting a reaction between the 4-position of the flavin and Cys138. The binding of 6-thiocyanato-FAD to the apoprotein of the mutated enzymes showed no evidence for a reaction between the thiols and the group at the 6-position of the flavin. PMID- 2229056 TI - Growth pattern of the murein sacculus of Escherichia coli. AB - The mechanism by which the murein sacculus of Escherichia coli is being enlarged during growth was investigated by pulse and pulse-chase labeling with [3H]diaminopimelic acid. Changes in the composition of the sacculus during aging were analyzed in detail by high performance liquid chromatography separation of the muropeptide subunits released after complete muramidase digestion. After pulses as short as 10 s, a group of novel phosphorylated muropeptides was detected. The kinetics of their appearance is consistent with these structures being derived from the undecaprenylphosphate-linked growing points of murein. A complex maturation process of murein took place including a rapid decay of pentapeptide side chains and a 10-fold increase in tripeptidyl moieties. In addition, the total degree of cross-linkage increased from 16 to 25%, partly due to a 3-fold increase in the formation of LD-A2pm-A2pm cross-links. In pulse-chase experiments the cross-linkage started to decrease after a maximum at about 35 min of chase. The kinetics in the distribution of the radioactivity among acceptor and donor part in the major cross-bridges Tetra-Tetra and Tetra-Tri differed from each other substantially, indicating that the latter structure is completely cleaved within three generations, whereas only 40% of Tetra-Tetra is cleaved during the same time. Furthermore, the attachment of the lipoprotein to murein was delayed by about one generation. It is proposed that these findings reflect an inside-to-outside growth mechanism of the murein sacculus of E. coli. PMID- 2229057 TI - Important role of arginine 129 in heparin-binding site of antithrombin III. Identification of a novel mutation arginine 129 to glutamine. AB - An hereditary abnormal antithrombin III (ATIII Geneva) with defective heparin cofactor activity was characterized by DNA single strand amplification and subsequent direct sequencing. ATIII Geneva was found to have a G to A transition in Exon IIIa leading to an Arg-129 to Gln mutation. This amino acid is part of the ATIII region comprising residues 114-154, which contains the highest proportion of basic residues (Arg or Lys), and is known from chemical modification studies to be involved in heparin binding. The variant protein did not bind heparin-Sepharose and was isolated from the propositus plasma by immunoaffinity chromatography. High affinity (for ATIII) heparin had only a minimal effect on thrombin and activated factor X inhibition by the purified abnormal ATIII. Taken together, these results demonstrate an important role for Arg-129 in the binding and interaction of ATIII with heparin of high affinity. We propose that a cooperation between Lys-125, Arg-129, Lys-136, and Arg-47 exposed at the surface of the inhibitor allows the binding of the essential pentasaccharide domain of heparin which is specific for the ATIII interaction. PMID- 2229058 TI - Characterization of bacteriophage T4 regA protein-nucleic acid interactions. AB - The bacteriophage T4 regA protein is a translational repressor of a group of T4 early mRNAs. We have characterized the binding of regA protein to polynucleotides and to specific RNAs. Binding to nucleic acids was monitored by the quenching of the intrinsic tryptophan fluorescence of regA protein. regA protein exhibited differential affinities for the polynucleotides examined, with the order of affinity being poly(rU) greater than poly(dT) greater than poly(dU) = poly(rG) greater than poly(rC) = poly(rA). The binding site size calculated for regA protein binding to poly(rU) was n = 9 +/- 1 nucleotides. Cooperativity was observed in binding to multiple-site oligonucleotides, with a cooperativity parameter (omega) value of 10-22. To study the specific interaction between regA protein and T4 gene 44 mRNA, the affinity of regA protein for synthetic gene 44 RNA fragments was measured. The association constant (Ka) for regA protein binding to gene 44 RNA fragments was 100-fold higher than for binding to nontarget RNA. Study of variant gene 44 RNA fragments indicated that the nucleotides required for specific binding are contained within a 12-nucleotide sequence spanning -12 to -1, relative to the AUG codon. The bases of five nucleotides (indicated in upper case type) are critical for specific regA protein interaction with the gene 44 recognition element, 5'-aaUGAGgAaauu-3'. These studies further showed that formation of a regA protein-RNA complex involves a maximum of 2-3 ionic interactions and is primarily an enthalpy-driven process. PMID- 2229059 TI - Translation of c-myc mRNA is required for its post-transcriptional regulation during myogenesis. AB - During the differentiation of C2 myoblasts into differentiated myotubes, there is a marked decrease in the abundance of c-myc mRNA. c-myc transcription initiation and elongation do not change significantly, but the turnover of c-myc transcripts appears to be accelerated during differentiation. We examined the expression of several recombinant c-myc genes introduced into C2 cells by stable transfection and found that mRNAs containing the c-myc protein-coding region of exons 2 and 3 are appropriately regulated; the upstream c-myc sequences, the long leader sequence encoded by c-myc exon 1, and the 3' untranslated region are dispensible for proper regulation. Regulation appears to affect c-myc transcripts that are bound to polyribosomes, and the mRNA from a gene with a point mutation in the translation initiation codon is no longer properly regulated. We conclude that down-regulation of c-myc expression during myogenesis is post-transcriptional and requires the presence of sequences encoding the c-myc protein in a form that can be translated. PMID- 2229060 TI - Murine complement C2 and factor B genomic and cDNA cloning reveals different mechanisms for multiple transcripts of C2 and B. AB - Murine genomic and cDNA clones were isolated to ascertain the mechanisms accounting for previously recognized multiple forms of complement C2 and factor B mRNA and to analyze structural similarities with the corresponding human gene products (C2, 74% and B, 85%, amino acid identity). Like the human Bf gene, murine Bf and C2 each consist of 18 exons with similar intron-exon organizations. The murine C2 gene (20 kilobases) is more than three times the size of Bf (6 kilobases) due to the presence of large intronic segments separating the exons encoding the NH2-terminal binding and central (von Willebrand factor) domains. Evidence from cDNA clones shows that the two C2 transcripts are generated by an alternative splice at the donor site of exon 14 producing long and short C2 mRNA species that differ by 21 base pairs encoding a region within the binding pocket (amino acids 636-642 (GSTCKDH)) of the serine proteinase domain. Tissue-specific multiple factor B transcripts are generated by alternative transcriptional initiation. From the structure of these transcripts the predicted regulation of expression and rates of translation of B programmed by the short and long mRNA species may differ, but the polypeptides are identical. These data indicate that different molecular mechanisms account for the multiple forms of C2 and factor B mRNA and that the structure of the different transcripts predicts differences in function and expression of the respective gene products. PMID- 2229061 TI - Regulation of transcriptional initiation in yeast mitochondria. AB - We have investigated in vitro transcriptional initiation by purified yeast mitochondrial RNA polymerase using a variety of previously described promoter variants and dinucleotides corresponding to the first two transcript nucleotides. Regardless of the actual nucleotides that occupy the first two transcript positions, the rate of initiation increases with increasing concentrations of the first two ribonucleoside triphosphates up to 125 microM whereas elongation is carried out optimally with less than 10 microM. Under normal in vitro transcription conditions, mitochondrial RNA polymerase only employs the in vitro start site (+1 position), again without regard to the nucleotide at the position. Even with initiator dinucleotide monophosphates as primers, the polymerase is only capable of initiating transcription at this position and one other, i.e. 1 base upstream (-1). Dinucleotides enhance transcription from partially active variant promoters (mutations around the initiation sites -3, -1, +1, +2), suggesting that these mutations reduce transcription by their effects on initiation. In contrast, inactive promoters (-7C, -6G, -4A, and -2A) are not active in the presence of initiating dinucleotide. We suggest that dinucleotides may function in one of three ways: (i) bypassing the energy barrier in forming the first internucleotide bond; (ii) stabilizing the initiation complex; or (iii) accelerating promoter clearance. PMID- 2229062 TI - The Ch21 protein, developmentally regulated in chick embryo, belongs to the superfamily of lipophilic molecule carrier proteins. AB - Ch21, a developmentally regulated low molecular weight protein observed in chick embryo skeletal tissues, is expressed "in vitro" by differentiating chondrocytes at a late stage of development. Here we report the complete amino acid sequence of the protein. 86% of the total amino acid sequence was deduced by sequences of 17 high performance liquid chromatography-separated proteolytic fragments and 33 amino acid residues at the amino-terminal end of protein purified from spent culture medium of hypertrophic chondrocytes. Furthermore we isolated by molecular cloning the corresponding cDNA and determined its nucleotide sequence. By combining protein and nucleotide sequence data we determined the primary structure of the entire Ch21. It consists of 158 amino acids and has a molecular mass of 18.065 kDa. Computer-assisted analysis showed that the Ch21 belongs to the superfamily of low molecular weight proteins sharing a basic framework for binding and transport of small hydrophobic molecules. PMID- 2229063 TI - Serum transferrin receptor is a truncated form of tissue receptor. AB - Recent studies have provided immunological evidence for the existence of transferrin receptor in human serum and have revealed that its concentration is a sensitive measure of erythropoiesis and iron deficiency. The present study was undertaken to establish the molecular identity of this immunoreactive component. Purification from human serum was accomplished by immunoaffinity chromatography using, as the ligand, monoclonal antitransferrin receptor antibody. The receptor preparation contained two major components with Mr of 75,000 and 85,000, which were identified as transferrin and transferrin receptor, respectively. The physicochemical and immunochemical properties of the 85,000 serum receptor were compared with those established for intact placental transferrin receptor. The serum receptor exhibited an apparent Mr = 85,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis under non-reducing conditions, as compared with 190,000 for placental transferrin receptor. Upon reduction, the Mr of serum receptor was unaltered, whereas, the 190,000 placental receptor dimer decreased to the expected monomer value of 95,000. Amino-terminal amino acid sequence analysis revealed that residues 1-19 of serum receptor were identical to residues 101-119 of intact receptor. These findings provide physicochemical evidence for the existence of transferrin receptor in human serum, establish its molecular identity as a truncated form lacking the cytoplasmic and transmembrane domains (residues 1-100) of intact receptor, and demonstrate that it exists as a transferrin-receptor complex in serum. PMID- 2229064 TI - Catalytic mechanism of xylose (glucose) isomerase from Clostridium thermosulfurogenes. Characterization of the structural gene and function of active site histidine. AB - The gene coding for thermophilic xylose (glucose) isomerase of Clostridium thermosulfurogenes was isolated and its complete nucleotide sequence was determined. The structural gene (xylA) for xylose isomerase encodes a polypeptide of 439 amino acids with an estimated molecular weight of 50,474. The deduced amino acid sequence of thermophilic C. thermosulfurogenes xylose isomerase displayed higher homology with those of thermolabile xylose isomerases from Bacillus subtilis (70%) and Escherichia coli (50%) than with those of thermostable xylose isomerases from Ampullariella (22%), Arthrobacter (23%), and Streptomyces violaceoniger (24%). Several discrete regions were highly conserved throughout the amino acid sequences of all these enzymes. To identify the histidine residue of the active site and to elucidate its function during enzymatic xylose or glucose isomerization, histidine residues at four different positions in the C. thermosulfurogenes enzyme were individually modified by site directed mutagenesis. Substitution of His101 by phenylalanine completely abolished enzyme activity whereas substitution of other histidine residues by phenylalanine had no effect on enzyme activity. When His101 was changed to glutamine, glutamic acid, asparagine, or aspartic acid, approximately 10-16% of wild-type enzyme activity was retained by the mutant enzymes. The Gln101 mutant enzyme was resistant to diethylpyrocarbonate inhibition which completely inactivated the wild-type enzyme, indicating that His101 is the only essential histidine residue involved directly in enzyme catalysis. The constant Vmax values of the Gln101, Glu101, Asn101, and Asp101 mutant enzymes over the pH range of 5.0 8.5 indicate that protonation of His101 is responsible for the reduced Vmax values of the wild-type enzyme at pH below 6.5. Deuterium isotope effects by D-[2 2H]glucose on the rate of glucose isomerization indicated that hydrogen transfer and not substrate ring opening is the rate-determining step for both the wild type and Gln101 mutant enzymes. These results suggest that the enzymatic sugar isomerization does not involve a histidine-catalyzed proton transfer mechanism. Rather, essential histidine functions to stabilize the transition state by hydrogen bonding to the C5 hydroxyl group of the substrate and this enables a metal-catalyzed hydride shift from C2 to C1. PMID- 2229065 TI - Interaction of lipoproteins with isolated ovary plasma membranes. AB - Plasma membranes of ovarian luteal and adrenal cortical cells from "microvillar channels," a unique extracellular compartment formed by the close apposition of flattened microvillar surfaces. Microvillar channels have unusual affinity for cholesterol-rich lipoproteins, and, in vivo, may provide an increased surface area for these particles. In this research, we have isolated a plasma membrane enriched fraction from rat luteinized ovaries, in which closely apposed membrane (i.e. microvillar channels) comprise about 30% of the preparation. Following in vitro incubations (approximately 1 h) of this plasma membrane fraction with different plasma lipoproteins, the closely apposed plasma membrane surfaces widen and become filled with lipoprotein particles (up to about 30 nm), whereas other membranes of the fraction show little binding. Competition experiments show that rat high density lipoproteins have the highest affinity for binding to the plasma membrane fraction. Radiolabeled plasma lipoprotein and the tissue-specific hormone, human chorionic gonadotropin, showed specific and saturable binding to the plasma membrane fraction, whereas other macromolecules used as controls did not. Radioautographic analyses of 125I-labeled lipoproteins and human chorionic gonadotropin indicate that binding occurs predominantly to the closely apposed plasma membranes (i.e. microvillar channels of the fraction). These studies show that microvillar channels of steroid-secreting cells entrap large numbers of plasma lipoproteins, particularly high density lipoproteins particles, presumably functioning in the delivery of cholesterol to these cells. PMID- 2229066 TI - Mechanisms involved in the transcriptional activation of proenkephalin gene expression in bovine chromaffin cells. AB - Stimulation of cultured bovine chromaffin cells with histamine (10(-5) M), nicotine (10(-6) M), and veratridine (2 x 10(-6) M) results in a time-dependent up to 5-fold increase in proenkephalin (Penk) mRNA levels. After an initial lag phase (with no major alterations) Penk mRNA increased markedly between 6 and 12 h followed by a slower, steady increase up to 48 h. The nicotinic receptor antagonist tubocurarine (4 x 10(-7) M) and the Ca2+ channel blocker D600 (10(-5) M) prevent the subsequent rise of Penk mRNA levels after challenge with nicotine, when given within the lag phase (0-6 h), suggesting the need of continuous receptor occupation and Ca2+ entry for induction of gene expression. Similarly, incubation of chromaffin cells with cycloheximide (10(-6) M), given at 0-6 h, blocks the increase in Penk mRNA after stimulation with histamine and nicotine indicating that ongoing protein synthesis is necessary for the delayed rise of Penk mRNA. Nuclear run-off experiments revealed high transcription levels of the Penk gene (3-fold at 2 h) and the tyrosine hydroxylase gene (7-fold at 20 min) following stimulation with histamine, which was not observed in the presence of cycloheximide (10(-5) M). A more rapid induction of transcription was measured for the c-fos gene after histamine stimulation (high levels after 12 min) followed by c-fos mRNA accumulation (about 20-fold after a 1-h stimulation), which was superinduced when cells were pretreated with cycloheximide. The half life of Penk mRNA levels (about 12 h), however, seems not to be affected by histamine as suggested by measurement of the subsequent decay of Penk mRNA levels after addition of alpha-amanitin or alpha-amanitin and cycloheximide. Thus, activation of Penk gene expression upon neurotransmitter challenge is suggested to be due to an enhanced transcriptional activity of the gene mediated by de novo synthesized protein (-like) factors. PMID- 2229067 TI - Characterization of U6 small nuclear RNA cap-specific antibodies. Identification of gamma-monomethyl-GTP cap structure in 7SK and several other human small RNAs. AB - The cap structure in human U6 small nuclear (sn)RNA, gamma-monomethylguanosine triphosphate (meGTP), was conjugated to human serum albumin and used as antigen to raise polyclonal antibodies in rabbits. The resulting antibodies reacted specifically with meGTP but not with GTP, GDP, GMP, meGMP, meATP, meCTP, meUTP, or with methyl phosphate in enzyme-linked immunosorbent assay and/or in radioimmunoassays. Although less efficiently, meGDP was also recognized by these antibodies. Indirect immunofluorescence studies with anti-meGTP antibodies showed predominantly nuclear immunofluorescence. Anti-meGTP antibodies immunoprecipitated intact U6 snRNA from a mixture of HeLa cell RNAs. In addition to the U6 snRNA, anti-meGTP antibodies immunoprecipitated several additional small RNAs that varied in length from approximately 50 to 330 nucleotides. These RNAs contained the meGTP cap structure and are structurally distinct from U6 snRNA. One of these meGTP-containing RNAs was found to be previously characterized 7SK RNA; human 7SK RNA synthesized in vitro also contained the same cap structure. Results obtained in this study provide evidence for the presence of gamma-monomethyl-GTP cap structure in a wide spectrum of human cellular RNAs. These antibodies will be useful in studying the structure and function of this new family of small RNAs. PMID- 2229068 TI - Expression of human immunodeficiency virus 1 (HIV-1) envelope gene products transcribed from a heterologous promoter. Kinetics of HIV-1 envelope processing in transfected cells. AB - The expression of human immunodeficiency virus 1 (HIV-1) envelope glycoprotein products was studied in cells transfected with env gene constructs transcribed from an SV40 promoter. Gene constructs possessing the complete tat, rev (tat+ rev+) and env genes were transiently expressed in COS-1 cells as precursor SU-TM (gp160), SU.TM (gp120 x 41), and nucleolar rev protein. In addition, envelope glycoprotein was detected on the surface of those transfected COS-1 cells expressing abundant levels of env protein. Transfected constructs possessing a mutated tat translational initiation codon (tat-rev+) were expressed in COS-1 cells with at least a 10-fold increase in the level of envelope glycoprotein expression compared to the analogous constructs with an intact tat AUG codon (tat+ rev+). Mutation of the rev initiation codon (tat+ rev-) and (tat-rev-) resulted in no detectable expression of env products but expression of these proteins could be rescued by co-transfection of a cDNA encoding the rev gene. Subgenomic tat/rev transcripts were detected following transfection of all of the gene constructs indicating splicing of the env mRNAs transcribed from a heterologous promoter. Unspliced env transcripts were only detected in the cytoplasm of cells transfected with (rev+) constructs or with the (tat- rev-) construct in the presence of the rev cDNA supplied in trans. In contrast, unspliced transcripts were detected in the nuclear and total cellular RNA of all transfected cells. Expression of rev protein was localized to the nucleolus of transfected COS-1 cells. These results indicate that the export of unspliced env mRNA to the cytoplasm is facilitated by the expression of rev. Following env synthesis, the conversion of SU-TM (gp160) to SU.TM (gp120 x 41) was not quantitative. After a 20-h pulse-chase, only 40% of the SU-TM (gp160) present at the start of the chase period was subsequently accountable as mature SU (gp120), and approximately 30% of the detectable SU (gp120) was found in the culture medium of transfected COS-1 cells. The findings indicate that the surface expression of SU.TM (gp120 x 41) derived from heterologous gene transcripts is modulated (i) the co-expression of rev, (ii) the efficiency of proteolytic processing of SU-TM (gp160), and (iii) the degree of SU (gp120) shedding and/or secretion from the cell. PMID- 2229069 TI - Retinoylation of HL-60 proteins. Comparison to labeling by palmitic and myristic acids. AB - Recent studies suggest that a retinoic acid (RA) nuclear receptor or a retinoylated nuclear protein may be involved in the action of RA. We showed previously (Takahashi, N., and Breitman, T. R. (1989) J. Biol. Chem. 264, 5159 5163) that retinoylation involves the formation of a thioester bond and occurs on protein in newly formed cells and in pre-existing cells. In this study, we saw at least 14 retinoylated proteins in HL-60 cells. Greater than 90% of the retinoylation was associated with the nuclear protein described previously. This protein, partially purified from isolated nuclei, bound to DNA-cellulose and was eluted with NaCl. Retinoylation occurred in HL-60 cells exposed to cycloheximide. Thus, retinoylation resembled palmitoylation, both in the covalent bond and the exchangeable reaction involving preformed protein. These similarities prompted us to compare retinoylation with two other fatty acylations in growing HL-60 cells. We found that the major retinoylated protein was labeled by either radioactive palmitic acid or myristic acid. The extent of [3H]palmitic acid labeling of this protein was not reduced by growth in the presence of RA. The extent of retinoylation of this protein was not reduced by growth in the presence of increasing concentrations of palmitic acid. These results raise the possibility that the same protein is a substrate for retinoylation, palmitoylation, and myristoylation. PMID- 2229070 TI - Large scale purification and immunolocalization of bovine uroplakins I, II, and III. Molecular markers of urothelial differentiation. AB - The differentiation of mammalian urothelium culminates in the formation of asymmetrical unit membrane (AUM). Using gradient centrifugation and detergent wash, we purified milligram quantities of AUMs which, interestingly, contained three major proteins (15, 27, and 47 kDa) that appeared to be identical to the three immunoaffinity purified, putatively AUM-associated proteins that we described earlier (Yu, J., Manabe, M., Wu, X.-R., Xu, C., Surya, B., and Sun, T. T. (1990) J. Cell Biol., 111, 1207-1216). Peptide mapping and immunoblotting established that these three proteins were distinct molecules. Using monospecific antibodies to these three proteins, we showed that they were all restricted to the superficial urothelial cells and were AUM-associated. The 27- and 15-kDa proteins were detected exclusively on the luminal side of mature, apical AUMs. In contrast, epitopes of the 47-kDa protein were detected on both sides of apical AUMs suggesting a transmembranous configuration. These results (i) provide the strongest evidence thus far that AUM contains three major proteins (the 27-kDa uroplakin I, 15-kDa uroplakin II, and 47-kDa uroplakin III) which form an extremely insoluble complex, (ii) suggest that uroplakin II, like uroplakin I (Yu, J., Manabe, M., Wu, X.-R., Xu, C., Surya, B., and Sun, T.-T. (1990) J. Cell. Biol. 111, 1207-1216), translocates from one side of the membrane to another during AUM maturation, (iii) indicate that uroplakin III may play a different structural role than uroplakins I and II in AUM formation, and (iv) establish the three uroplakins as markers for an advanced stage of urothelial differentiation. PMID- 2229071 TI - The mitochondrial tRNAs of Trypanosoma brucei are nuclear encoded. AB - The mitochondrial DNA of Trypanosoma brucei is organized as a catenated network of maxicircles and minicircles. The maxicircles are equivalent to the typical mitochondrial genome except that the genes for the mitochondrial tRNAs have not been identified by sequence analysis of the maxicircle DNA. The apparent absence of tRNA genes in the maxicircle DNA suggests that the mitochondrial tRNAs are encoded by either the minicircle or the nuclear DNA. In order to determine their genomic origin, we isolated and identified the mitochondrial tRNAs of T. brucei. We show that these mitochondrial tRNAs are truly mitochondrially located in vivo and that they are free from detectable contamination by cytosolic RNAs. By hybridization analysis, using mitochondrial tRNAs as the probe, we determined that the mitochondrial tRNAs are encoded by nuclear DNA. This implies that RNAs, like proteins, are imported into the mitochondria. We investigated the relationship between the cytosolic and the mitochondrial tRNA genes and show that there are unique cytosolic tRNA genes, unique mitochondrial tRNA genes, and tRNA genes which appear to be shared and whose products are therefore targeted to both the cytosol and the mitochondrion. PMID- 2229072 TI - The MAS-encoded processing protease of yeast mitochondria. Overproduction and characterization of its two nonidentical subunits. AB - The amino-terminal presequences of proteins imported from the cytoplasm across the mitochondrial inner membrane are cleaved off by a soluble matrix-localized protease composed of two nonidentical homologous subunits. In the yeast Saccharomyces cerevisiae, these are encoded by the nuclear MAS1 and MAS2 genes. We have now constructed yeast strains in which either one or both of the genomic MAS genes are controlled by a galactose-inducible strong promoter. In these strains, the intramitochondrial concentration of each MAS-encoded subunit as well as of the holo-protease can be varied over a wide range. When overproduced, the MAS1 protein precipitates in the matrix whereas the MAS2 protein remains soluble. The MAS2 protein was obtained at a purity of 98% in milligram amounts. The purified MAS2 subunit exists largely as a soluble 52-kDa monomer. Its cleavage activity is very low and might well reflect the 2% contamination by holoprotease. Activity is restored by adding the solubilized purified MAS1 subunit. Yeast cells depleted of one or both MAS subunits continue to import precursor proteins into mitochondria, but fail to cleave them; eventually the deficient cells stop growing. This growth arrest is partly suppressed on minimal medium or under conditions in which the cells are less dependent on mitochondrial metabolism. Depletion of the MAS1 subunit causes overproduction of the MAS2 subunit. PMID- 2229073 TI - A second fibronectin-binding region is present in collagen alpha chains. AB - The interactions of plasma fibronectin with alpha chains or cyanogen bromide fragments of collagen types I and II have been studied using a variety of techniques. Affinity chromatography of cyanogen bromide-cleaved type II collagen on immobilized fibronectin revealed the binding of cyanogen bromide fragment CB12 in addition to the previously characterized CB10. Using fluorescence polarization, we analyzed the interaction between the collagen peptides and fluorescein isothiocyanate-labeled 42-kDa gelatin-binding fragment of fibronectin in solution. Dissociation constants for the binding of CB10 and CB12 to the fibronectin fragment were calculated as 0.38 and 0.94 microM, respectively, indicating a lower affinity for the uncharacterized site. However, as with CB10, CB12 was able to compete effectively with the intact alpha chain for bindinng to fibronectin. Additionally, both CB10 and CB12 absorbed to tissue culture surfaces were each able to support fibronectin-dependent cell adhesion. Finally, the regions of alpha 2(I) homologous to CB12 and CB10 were found to be active in fibronectin binding, demonstrating the presence of two fibronectin-binding regions in this collagen chain. PMID- 2229074 TI - Aggregated dnaA protein is dissociated and activated for DNA replication by phospholipase or dnaK protein. AB - dnaA protein isolated from Escherichia coli is equally distributed between a monomeric form, which is active for initiation of DNA replication, and an inactive, aggregated form which contains phospholipids. Replication activity of the aggregated form can be restored by treatments with either dnaK protein or phospholipase A2. Dissociation of the aggregate by dnaK protein is driven by ATP hydrolysis; action by phospholipase A2 requires a minute concentration of ATP only to stabilize the dissociated protein. Conversion of inactive dnaA phospholipid complexes to the active form may contribute to the regulation of the initiation of chromosomal replication in E. coli. PMID- 2229075 TI - Apolipoprotein B messenger RNA editing in the rat liver. Modulation by fasting and refeeding a high carbohydrate diet. AB - Apolipoprotein B (apoB) mRNA is modified by a posttranscriptional editing reaction in which a single base (C to U) change in apoB100 mRNA modifies a glutamine (CAA) to a translational stop codon (UAA), producing apoB48 mRNA in mammalian intestine. Rat liver normally contains both edited and unedited apoB mRNAs and previous work (Davidson, N. O., Powell, L. M., Wallis, S. C., and Scott, J. (1988) J. Biol. Chem. 263, 13482-13485) has demonstrated that the introduction of a translational stop codon can be modulated by thyroid hormone. In the current study, hepatic lipogenesis was modulated in vivo by fasting and refeeding a high carbohydrate diet, a maneuver which produced a 30-fold increase in hepatic triglyceride content. In this setting, hepatic apoB100 synthesis became undetectable in animals subjected to 48 h fasting and subsequently refed a high carbohydrate diet for either 24 or 48 h. This change was accountable for by an increase in the proportion of edited apoB mRNA, as determined by primer extension analysis, from 37% UAA in fasted animals to 79 and 91% UAA at 24 and 48 h of refeeding, respectively. The effect of this regimen on the expression of other hepatic apolipoprotein genes was less dramatic. ApoA-I and apoA-IV gene expression was modulated over a 2-fold range, in contrast to the (6-14-fold) pretranslational changes induced by thyroid hormone administration. ApoCIII mRNA abundance was unaltered in the setting of either fasting and refeeding or thyroid hormone administration, while apoE gene expression demonstrated a pretranslational increase following prolonged fasting. Taken together the data provide evidence that apoB mRNA editing is modulated by alterations in hepatic lipogenesis which additionally produce effects on the expression of other hepatic apolipoprotein genes suggesting that they are not coordinately regulated in vivo. PMID- 2229076 TI - Reconstitution of the uncoupling protein of brown adipose tissue mitochondria. Demonstration of GDP-sensitive halide anion uniport. AB - The fluorescent anion indicator 6-methoxy-N-(3-sulfopropyl)quinolinium was trapped in proteoliposomes reconstituted with purified 32-kDa uncoupling protein and used to detect GDP-sensitive uniports of Cl-, Br-, and I-. Transport of these halide anions was rapid and potential-dependent. F- and nitrate were found to inhibit Cl- uptake competitively, suggesting that these anions are also substrates for transport. This preparation also exhibited H+(OH-) transport, showing that the reconstituted uncoupling protein possesses both halide and H+ transport functions, as is observed in intact brown adipose tissue mitochondria. Cl- transport was inhibited to the residual level observed in liposomes without protein when GDP was present on both sides of the membrane. Cl- transport was inhibited by about 50% when GDP was present only on one side of the membrane. We infer that uncoupling protein reconstitutes into proteoliposomes with a 1:1 ratio of sidedness orientation. The Km values for Cl- uniport were 100 and 65 mM, respectively, in GDP-loaded and non-GDP-loaded vesicles. Participation of the inner membrane anion channel in the observed transport is rendered unlikely by the fact that this carrier is insensitive to GDP. A variety of additional experiments probing for inner membrane anion channel yielded uniformly negative results, confirming the absence of contamination by this protein. Our results therefore demonstrate that the uncoupling protein mediates anion translocation, a function previously reported as lacking in the reconstituted system. PMID- 2229077 TI - New substrates and competitive inhibitors of the Cl- translocating pathway of the uncoupling protein of brown adipose tissue mitochondria. AB - A large number of new substrates for anion uniport by the uncoupling protein of brown adipose tissue mitochondria have been found. These include alkylsulfonates, alkylsulfates and their derivatives, benzenesulfonate, oxohalogenides, hypophosphate, hexafluorophosphate, and pyruvate. Although the spectrum of anion selectivity is far wider than had previously been suspected, there are strong structural requirements for transport. The anion must be monovalent, and polar groups must not be attached to alkyl or aryl chains. The most striking finding is that transport increases dramatically with anion hydrophobicity. Anions that are transported are shown to compete with Cl- for transport by the reconstituted uncoupling protein. For each anion, the Ki for GDP inhibition of transport increases with its rate of transport and correlates inversely with its Ki for competitive inhibition of Cl- transport. For alkylsulfonates, transport rate, Ki for GDP inhibition, and Ki for inhibition of Cl- transport each depend monotonically on alkyl chain length. These findings suggest several new hypotheses relating to the molecular mechanism of transport through uncoupling protein and suggest explanations for observed functional differences among porters belonging to the same gene family. PMID- 2229078 TI - Purification and characterization of sea urchin initiation factor 2. The requirement of guanine nucleotide exchange factor for the release of eukaryotic polypeptide chain initiation factor 2-bound GDP. AB - Protein synthesis in sea urchin eggs is stimulated dramatically upon fertilization. We previously demonstrated that this stimulation is primarily due to an increase in the rate of polypeptide chain initiation which in turn may be regulated at the level of recycling of eukaryotic initiation factor 2 (eIF-2) (Colin, A. M., Brown, B. D., Dholakia, J. N., Woodley, C. L., Wahba, A. J., and Hille, M. B. (1987) Dev. Biol. 123, 354-363). We have now purified eIF-2 from sea urchin Strongylocentrotus purpuratus blastulae to apparent homogeneity by chromatography on DEAE-cellulose, phosphocellulose, Mono Q, Mono P, and Mono S columns. The factor, which differs from mammalian eIF-2, is composed of three non identical subunits with apparent molecular weights of 40,000-alpha; 47,000-beta, and 58,000-gamma as estimated by sodium dodecyl-polyacrylamide gel electrophoresis. Antibodies raised against rabbit reticulocyte eIF-2 do not cross react with sea urchin eIF-2. The binding of Met-tRNA(f) to sea urchin eIF-2 is totally dependent on GTP. A 4-fold stimulation in the rate of protein synthesis in unfertilized sea urchin egg extracts is observed by the addition of 1 micrograms of purified eIF-2. The factor also binds GDP to form a binary (eIF 2.GDP) complex which is stable in the presence of Mg2+. GDP binding to sea urchin eIF-2 inhibits ternary (eIF-2-GTP.[35S]Met-tRNA(f) complex formation. The rabbit reticulocyte guanine nucleotide exchange factor (GEF) catalyzes the exchange of GDP bound to sea urchin eIF-2 for GTP and stimulates ternary complex formation. The requirement of GEF for the recycling of eIF-2 suggests that protein synthesis in sea urchins is similar to that in mammalian systems and may also be regulated at the level of GEF activity. The reticulocyte heme-controlled repressor phosphorylates the alpha-subunit of eIF-2 from both sea urchins and rabbit reticulocytes. However, casein kinase II which phosphorylates the beta-subunit of the reticulocyte factor specifically phosphorylates the alpha-subunit of sea urchin eIF-2. In this respect, the sea urchin factor is similar to eIF-2 isolated from other nonmammalian sources. Since both heme controlled repressor and casein kinase II phosphorylate the alpha-subunit of sea urchin eIF-2 caution should be exercised when interpreting the significance of eIF-2(alpha) phosphorylation in sea urchins. PMID- 2229079 TI - Thyrotropin modulates low density lipoprotein binding activity in FRTL-5 thyroid cells. AB - FRTL-5 cells possess high affinity low density lipoprotein (LDL) receptors which bind, internalize, and degrade LDL. When FRTL-5 cells are deprived of thyrotropin (TSH) the binding of LDL increases more than 2-fold. Upon addition of TSH, at a concentration of 1 x 10(-10) M or greater, LDL binding decreases rapidly and within 24 h reaches the level which is typical of FRTL-5 cells chronically stimulated by TSH. The data available suggest that TSH-dependent down-regulation of LDL receptor activity is exerted through a reduction of the number of active LDL receptors, with no change in affinity. It is unlikely that the synthesis of LDL receptors is impaired, since LDL receptor messenger RNA is not decreased by TSH. The effect of the hormone on LDL receptor activity can be mimicked by 8-Br cAMP and is completely abolished by the protein synthesis inhibitor cycloheximide but not by actinomycin D. TSH regulation of LDL receptor activity is lost in v ras Ki-transformed FRTL-5 cells (Ki Mol) which also have lost TSH dependence for adenylate cyclase activation and growth. However, 8-Br-cAMP decreases LDL binding in Ki Mol FRTL-5 cells. The reduced availability of LDL receptor in TSH stimulated FRTL-5 cells may be related to the increased membrane fluidity (Beguinot, F., Beguinot, L., Tramontano, D., Duilio, C., Formisano, S., Bifulco, M., Ambesi-Impiombato, F. S., and Aloj, S. M. (1987) J. Biol. Chem. 262, 1575 1582) or may reflect increased degradation of LDL receptors. We propose that a lower cholesterol uptake is needed in an actively proliferating cell population, to increase the production of isoprenoids whether it be for cholesterol biosynthesis or for the synthesis of other compounds requiring isoprenoid precursors. PMID- 2229080 TI - Cell cycle progression and 3-hydroxy-3-methylglutaryl coenzyme A reductase are regulated by thyrotropin in FRTL-5 rat thyroid cells. AB - The incorporation of [14C]acetate into cholesterol shows that FRTL-5 cells possess an active cholesterol biosynthetic pathway. When these cells were made quiescent, and synchronized by thyrotropin (TSH) starvation, in the presence of low serum (0.2%), addition of this hormone increased acetate conversion into cholesterol up to a maximum of 8-fold. Feedback inhibition of sterol synthesis by exogenous cholesterol occurs in FRTL-5 cells since, in the presence of higher serum concentration (5%), acetate conversion into cholesterol was significantly depressed. Even in high serum TSH increased sterol synthesis, albeit to a lesser extent. The time course of the TSH effect on cholesterol synthesis, strongly suggests that this process is necessary for quiescent FRTL-5 cells to enter the cell cycle. Thus, the rate of cholesterol synthesis was maximal 12-16 h after TSH challenge and declined thereafter, returning to levels slightly above the basal at 48 h. Thymidine incorporation into DNA, measured under identical conditions of TSH starvation/challenge, increased after 20 h, was maximal at 36 h, and returned to pre-TSH level at 70 h. The effect of TSH on cholesterol synthesis is not a general feature of lipid synthesis in FRTL-5 since [14C]acetate incorporation into triglycerides after TSH treatment has a different magnitude and time course. TSH increases cholesterol synthesis through the induction of the enzyme 3-hydroxy 3-methylglutaryl coenzyme A reductase. This is due to an increase in the level of 3-hydroxy-3-methylglutaryl-CoA reductase messenger RNA up to 8-fold caused by a proportional increase in the rate of gene transcription, as assessed by nuclear "run on" experiments. The effect of TSH on cholesterol synthesis and reductase gene expression is likely to be mediated by cAMP since 8-bromo-cAMP mimicked the effect of the hormone. The data presented suggest that an active cholesterol biosynthetic pathway is required for DNA synthesis to occur. PMID- 2229081 TI - A human ubiquitin carboxyl extension protein functions in yeast. AB - The ability of the human ubiquitin carboxyl extension protein (HUBCEP80) to functionally replace its yeast homolog was determined in a ubi3 mutant of Saccharomyces cerevisiae. Expression of HUBCEP80 in ubi3 mutants resulted in processing of the fusion protein to produce free ubiquitin and extension protein, the latter of which localized specifically with the 40 S ribosomal subunit. Furthermore, expression of the human fusion protein completely alleviated the phenotypic deficiencies found in ubi3 mutants, including slow growth, abnormal ribosomal RNA processing, and correspondingly low levels of 40 S ribosomal subunits. Finally, expression of the extension protein alone was much less efficient in complementing the ubi3 mutant phenotype as compared with expression of the normal ubiquitin-fused extension protein. In the latter case, cells were found to contain at least 5-fold more extension protein, suggesting that ubiquitin either increased translational efficiency of the HUBCEP80 transcript or increased the stability of the processed extension protein. PMID- 2229082 TI - Surface array protein of Campylobacter fetus. Cloning and gene structure. PMID- 2229083 TI - Wrist loading patterns during pommel horse exercises. AB - Gymnastics is a sport which involves substantial periods of upper extremity support as well as frequent impacts to the wrist. Not surprisingly, wrist pain is a common finding in gymnasts. Of all events, the pommel horse is the most painful. In order to study the forces of wrist impact, a standard pommel horse was instrumented with a specially designed load cell to record the resultant force of the hand on the pommel during a series of basic skills performed by a group of seventeen elite male gymnasts. The highest mean peak forces were recorded during the front scissors and flair exercises (1.5 BW) with peaks of up to 2.0 BW for some gymnasts. The mean peak force for hip circles at the center or end of the horse was 1.1 BW. The mean overall loading rate (initial contact to first loading peak) ranged from 5.2 BWs-1 (hip circles) to 10.6 BW s-1 (flairs). However, many recordings displayed localized initial loading spikes which occurred during 'hard' landings on the pommel. When front scissors were performed in an aggressive manner, the initial loading spikes averaged 1.0 BW in magnitude (maximum 1.8 BW) with an average rise time of 8.2 ms; calculated localized loading rates averaged 129 BW s-1 (maximum 219 BW s-1). These loading parameters are comparable to those encountered at heel strike during running. These impact forces and loading rates are remarkably high for an upper extremity joint not normally exposed to weight-bearing loads, and may contribute to the pathogenesis of wrist injuries in gymnastics. PMID- 2229084 TI - Pressure distribution on articular surfaces: application to joint stability evaluation. PMID- 2229085 TI - Effects of simulated weightlessness on bone properties in rats. PMID- 2229086 TI - Pulsatile two-dimensional flow and plaque formation in a carotid artery bifurcation. AB - Velocity and pressure fields, streamlines and wall shear stress distributions were numerically obtained for two-dimensional, steady and pulsatile flow in a carotid artery segment. Distinct regions of reverse flow near the bifurcation and wavy flow patterns in the branching channels were observed during portions of the pulse. These phenomena disappear at the end of the systolic phase of the cardiac cycle. A previously validated plaque formation model predicts that plaque sites and the local extent of atherosclerotic lesions are similar for those present on human angiograms. PMID- 2229087 TI - Estimating segment inertial properties: comparison of magnetic resonance imaging with existing methods. AB - To explore magnetic resonance imaging (MRI) as the basis of a technique for estimating body segment inertial properties directly on subjects, MRI-based estimates were compared with those generated with more traditional methods. The sensitivity of mass, center of mass location, and moment of inertia estimates to the estimation methods and the distribution of muscle, bone, and fat tissues in the lower leg were also evaluated. A series of transverse plane images spaced 2.5 cm apart on the right lower leg of 12 adult males were taken, using MRI. Cross sectional area data determined from the images served as the basis of the inertial calculations. MRI-based estimates for mass, center of mass location, and moment of inertia about a transverse axis through the center of mass all fell within the range of values obtained with other methods. While the center of mass position was similar for all estimation methods, MRI-based estimates of lower leg mass and moment of inertia showed considerable variability among methods. In addition, MRI mass and moment of inertia values were higher than those from most of the other prediction methods. It is suggested that the higher MRI-based estimates for these descriptors may be reasonable when age and structural differences between young adult runners and cadaver specimens for the comparison studies are considered. These results provide further support for MRI as a means of generating valid inertial property estimates. PMID- 2229088 TI - The decomposition of apparent stresses in disturbed pulsatile flow in the presence of large scale organized structures. AB - Flow disturbance phenomena that occur in unsteady-in-the-mean flows (i.e. pulsatile or oscillating) at moderate Reynolds numbers are analyzed in both the time domain and the frequency domain. The analysis utilizes variable decomposition into a time-varying underlying waveform and flow disturbances which are composed of large scale organized structures and random fluctuations. A practical technique which incorporates time domain phase conditioning, trend removal, and frequency domain matched filtering, is presented and examined using simulated data of known statistical behavior. The applicability of the method is shown by the decomposition of the simulated data and the technique is then applied to experimental data obtained in pulsatile flow through a constricted tube by means of a laser Doppler anemometer. The cross-sectional area reduction at the constriction throat was 90%. The Womersley parameter in the experiments was 5.3 and the Reynolds number based on the average flow rate per cycle was 300 with a minimum/maximum value of 55/600 based on the instantaneous flow rate. Measurements were taken in the flow region downstream of the constriction throat which included several interesting flow disturbance phenomena. The results of the decomposed flow phenomena demonstrate the significant role of large scale organized structures in such flows. This is particularly important when analyzing blood flow in the large arteries in the presence of severe stenosis or behind prosthetic devices in an attempt to estimate the 'turbulent' stress which act on cellular elements. Estimation of the apparent stress tensor is of importance in an effort to elucidate the mechanical factors which influence the durability of red blood cells under abnormal conditions. PMID- 2229089 TI - Three-dimensional determination of an oblique osteotomy in the hip by mathematical optimization fulfilling some anatomical demands. AB - The present paper describes a nonlinear optimization process to estimate the single cutting plane of an oblique osteotomy in the hip. This kind of osteotomy was introduced and practised by Charit (Research report 81, University of Witwaters brand, Johannesburg, 1981). We calculate the cutting plane in such a way that the postoperative coverage of the resulting two parts of the femur are as great as possible whereby some anatomical constraint conditions are fulfilled. Additionally a simplified preoperative planning is described by using a sphere lying on the femoral head and determined by a least-squares method. PMID- 2229090 TI - Optimal design parameters of the bicycle-rider system for maximal muscle power output. AB - The purpose of this study was to find the optimal values of design parameters for a bicycle-rider system (crank length, pelvic inclination, seat height, and rate of crank rotation) which maximize the power output from muscles of the human lower limb during bicycling. The human lower limb was modelled as a planar system of five rigid bodies connected by four smooth pin joints and driven by seven functional muscle groups. The muscles were assumed to behave according to an adapted form of Hill's equation. The dependence of the average power on the design parameters was examined. The instantaneous power of each muscle group was studied and simultaneous activity of two seemingly antagonistic muscle groups was analyzed. Average peak power for one full pedal revolution was found to be around 1100 W. The upper body position corresponding to this peak power output was slightly reclined, and the pedalling rate was 155 rpm for a nominal crank length of 170 mm. PMID- 2229091 TI - The importance of internal load in contractile models of muscles. PMID- 2229092 TI - Comment on 'stiffness and strain energy criteria to evaluate the threshold of injury to an intervertebral joint'. PMID- 2229093 TI - Niels Stensen's geometrical theory of muscle contraction (1667): a reappraisal. AB - From reading the Elementorum Myologiae Specimen of 1667 by Niels Stensen (Steno), I assert that the text and illustrations contain an observation-based theory on the mechanics of muscle contraction: (1) Based on the study of the structure and motion of several muscles in different animals and in man, Stensen described the contraction of parallel equally long motor fibers formated as uni- or multipennate structures, each forming a parallelepipedon between parallel tendon plates. The parallelepipedon was used as a model allowing Stensen to apply mathematical methods in the argumentation. When the motor fibers contract, the tendons move in parallel planes, the muscle shortens, but the distance between the tendon planes does not change. There will appear a swelling, even if the volume of the model remains the same. Therefore, the swelling observed during contraction, according to Stensen, is no argument for an increase in muscle bulk and no argument against contraction without any change of muscle volume. (2) In the first century after its proposal, different arguments were published against Stensen's theory: in 1680 by Borelli (De Motu Animalium), 1694 by Bernoulli (De Motu Musculorum), 1743 by Boerhaave (Praelectiones), and 1762 by Haller (Elementa Physiologiae). When read today, these arguments are irrelevant, erroneous, or without scientific documentation. However, by the end of the 18th century, Stensen's theory all but disappeared from the science literature. (3) Anatomical and biomechanical studies published after 1980 show that the foundation and applicability of Stensen's theory are still valid. (4) While earlier considered to be perhaps Stensen's weakest work, arguments are presented to reappraise Elementorum as one of Stensen's significant publications and as a significant work in the biomechanical sciences. PMID- 2229094 TI - Fracture mechanics of bone with short cracks. AB - Tensile fracture experiments were performed upon specimens of wet mature bovine Haversian bone, with short, controlled notches. Stress concentration factors were found to be significantly less than values predicted using a maximum stress criterion in the theory of elasticity. Results were also modeled with the aid of linear elastic fracture mechanics. Agreement of experiment with theory was better in this case, however deviations were seen for short notches. Two mechanisms were evaluated for the behavior: plasticity near the crack tip, and effects of the Haversian microstructure, modelled by Cosserat elasticity, a generalized continuum theory. Plastic zone effects were found to be insignificant. Cosserat elasticity, by contrast, predicted stress concentration factors which better approximated observed values. To explore strain redistribution processes, further experiments were conducted upon notched specimens in torsion at small strain. They disclosed a strain redistribution effect consistent with Cosserat elasticity. These microelastic effects were attributed to the Haversian architecture of bone. The implications of the results are that bone resists the effect of stress raisers such as fatigue microcracks and surgical sawcuts to a much greater extent than anticipated on the basis of its elastic or elastoplastic properties. PMID- 2229095 TI - Joint reaction forces at the first MTP joint in a normal elderly population. AB - The calculation of net ankle, knee, and hip joint reaction forces is an often applied procedure in the analysis of gait. Except for very few studies, joint reaction forces have not been measured in other joints such as the fingers, wrist, elbow, shoulder and toes. In this study the joint reaction forces between the metatarsal head and the proximal phalanx and the metatarsal head and the sesamoids are calculated for the push off phase during gait. The results of ten normal elderly subjects show that the maximum resultant loads of the two articulations lie close to the longitudinal axis of the metatarsal. The knowledge of the magnitude and direction of the joint reaction forces of a normal elderly population will be essential for the design of an optimal fixation of an artificial anatomical first MTP joint. PMID- 2229096 TI - Biomechanics of the venous wall under simulated arterial conditions. AB - The failure of vein graft conduits implanted in the arterial circulation has been hypothesized to occur in part due to the exposure of the graft to altered biomechanical and fluid shearing forces. In the present study, these forces are characterized for canine internal jugular veins (IJV) exposed to realistic arterial flow dynamics. Freshly excised vein segments were mounted into a pulsatile perfusion apparatus and exposed to arterial flow conditions (P = 115/75 mmHg and Q = 110 ml min-1) for 2 h. Dynamic measurements of intraluminal pressure and flow rate and vessel wall radial distension were acquired to accurately quantitate the incremental modulus of elasticity; hoop, axial and radial wall stresses; and fluid shearing forces within the vessel. Identical measurements were performed on canine carotid arteries (CCA) to serve as a comparison. Under arterial conditions, IJV segments demonstrated a significant elevation (p less than 0.05) over the CCA in the incremental elasticity modulus, along with a corresponding elevation in hoop and axial wall stresses. Additionally the average wall shearing rate to which the IJV endothelial surface was exposed was a factor of six less than that observed in the CCA. These results are discussed in relationship to the clinical situation of vein graft adaptation to arterial hemodynamics. PMID- 2229097 TI - Trends of mechanical consequences and modeling of a fibrous membrane around femoral hip prostheses. AB - In the present study, the effects of a fibrous membrane between cement and bone in a femoral total hip replacement were investigated. The study involved the problem of modeling this fibrous membrane in finite-element analyses, and its global consequences for the load-transfer mechanism and its resulting stress patterns. A finite-element model was developed, suitable to describe nonlinear contact conditions in combination with nonlinear material properties of the fibrous membrane. The fibrous tissue layer was described as a highly compliant material with little resistance against tension and shear. The analysis showed that the load transfer mechanism from stem to bone changes drastically when such a membrane is present. These effects are predominantly caused by tensile loosening and slip at the interface, and are enhanced by the nonlinear membrane characteristics. Using parametric analysis, it was shown that these effects on the load-transfer mechanism cannot be described satisfactorily with linear elastic models. Most importantly, the fibrous tissue interposition causes excessive stress concentrations in bone and cement, and relatively high relative displacements between these materials. PMID- 2229099 TI - Steady state plasma [3H]-noradrenaline kinetics in quadriplegic chronic spinal cord injury patients. AB - 1. Steady state plasma noradrenaline kinetics were measured in eight male quadriplegic patients and in eight age and sex matched controls. 2. Plasma noradrenaline levels were significantly lower in quadriplegic patients compared to controls. Noradrenaline spillover rate was markedly reduced in quadriplegics compared to controls while noradrenaline clearance was similar in both groups. 3. Noradrenaline kinetics in quadriplegic patients differ from peripheral autonomic neuropathy patients where reductions in both the spillover and clearance of noradrenaline are present. PMID- 2229100 TI - Heterogeneity of vascular muscarinic receptors. AB - Muscarinic receptors mediate diverse effects on the vasculature. Recently, a consensus has been arrived at with regard to muscarinic receptor classification (Levine & Birdsall, 1989). As a result, it may now be possible to clarify the role of each subtype in the responses of vascular tissues to muscarinic agonists. It is apparent that vascular muscarinic receptors form a heterogeneous population. M1 receptors contract canine venous tissue, whilst M3 receptors contract porcine and bovine coronary arteries. M3 receptors also mediate EDRF dependent relaxant responses in the majority of tissues studied to date. M2 receptors elicit relaxations by a decrease in sympathetic outflow in canine femoral vein, rabbit ear artery and rat portal vein. These conclusions are primarily derived from functional estimations of equilibrium dissociation constants, since comparable radioligand binding data are both scarce and contradictory. It is concluded that all three major subtypes of receptors are present in the vasculature. However, the limited selectivity of the available antagonists, the lack of extensive use of such compounds and the unavailability of selective agonists clearly indicate the need for more definitive studies to be undertaken. PMID- 2229098 TI - Cholecystokinin and cholinergic agents on periodic gallbladder contraction in dogs. AB - 1. The effect of cholecystokinin octapeptide (CCK-OP), methacholine, 2-deoxy-D glucose (2DG) and gastric distension on gallbladder contraction in relation to interdigestive activity was studied in four conscious dogs with chronic biliary fistulae. 2. The gallbladder contraction in response to CCK-OP was inhibited by atropine and by a ganglionic blocking agent, the characteristics suggesting competitive inhibition. 3. Spontaneous contraction of the gallbladder was still observed after the administration of CCK-OP, methacholine or 2DG. With ganglionic blockade, CCK(-)-OP or methacholine initiated gallbladder contraction, but the spontaneous peak was no longer observed. 4. CCK-OP (100 ng kg-1), methacholine or 2DG advanced the spontaneous contraction of the gallbladder, but did not alter the duration of the cycle. 5. Gastric distension initiated gallbladder contraction. This was abolished by ganglionic blockade. The contraction did not continue in spite of continuous gastric distension, and the spontaneous contraction reappeared 100 min following the pre-distension control. PMID- 2229101 TI - Results of treatment of displaced patellar fractures by partial patellectomy. AB - The results of partial patellectomy as a treatment for displaced patellar fractures were assessed retrospectively with use of clinical, radiographic, and isokinetic strength-testing criteria. Forty patients who had been followed for an average of 8.4 years were studied. In the extremity that had been operated on, the mean active range of motion was 94 per cent, the circumference of the thigh was 100 per cent, and the strength of the quadriceps was 85 per cent of these measurements in the contralateral extremity. The over-all result was rated as excellent in twenty patients, good in eleven, fair in six, and poor in three. There was a significant statistical correlation between the type of fracture and the outcome. The results of this study indicate that partial patellectomy can be an effective treatment for selected patellar fractures. PMID- 2229102 TI - Dealing with geographic variations in the use of hospitals. The experience of the Maine Medical Assessment Foundation Orthopaedic Study Group. AB - Orthopaedists and other physicians in Maine organized the Maine Medical Assessment Foundation to deal with the problem of variations in the rates of hospitalization for orthopaedic conditions. Five musculoskeletal injuries and five orthopaedic procedures were selected for study. The variation in decision making by orthopaedists was least for fractures of the ankle and fractures of the hip and was greatest for fractures of the forearm, derangement of the knee, and lumbosacral sprain. The rates in an area tended to be consistently high or low for the same treatments. The major reasons for the variations appeared to be related to lack of agreement about optimum treatment. Feedback of data to physicians on variations in patterns of practice reduced the variations. PMID- 2229103 TI - Unexpected geographic variation in rates of hospitalization for patients who have fracture of the hip. Medicare enrollees in the United States. AB - With the use of data from hospitals for fiscal year 1985, we calculated the rates of hospitalization for fracture of the hip, by state of residence, for all enrollees in Medicare who were sixty-five years old or older; we adjusted for age and race. The rate of fracture of the hip was highest in the South and lowest in the Northeast, especially in women. The cause of this difference is not known. PMID- 2229104 TI - Arthrometric evaluation of knees that have a torn anterior cruciate ligament. AB - We used the KT-1000 arthrometer to test the knees of 107 patients who had an acute tear of the anterior cruciate ligament, 153 patients who had a chronic tear, and 141 control subjects, for a total of 401 individuals. The three testing parameters were the extent of anterior translation at eighty-nine newtons of force and at maximum manual force, and the compliance index. The differences between the involved and the uninvolved knees were calculated. At eighty-nine newtons, all but one of the control subjects had anterior translation of ten millimeters or less, compared with 58 per cent of the patients who had a chronic tear. At maximum manual force, all but two of the control subjects had translation of ten millimeters or less, compared with 20 per cent of the patients who had an acute or a chronic tear. Analysis of variance showed that the clinical diagnosis correlated well with the results for all tests (p less than 0.001). However, when the uninjured knees of patients who had an acute or a chronic tear were compared with the knees of the control subjects, significant differences were noted (p less than 0.001 to 0.006). In the patients who had a chronic tear, there was no relationship between the time from injury to operation and the extent of anterior translation. The arthrometric test at maximum manual force was the strongest discriminant; it differentiated normal from abnormal knees (p less than 0.001) with high sensitivity (92 per cent), high specificity (95 per cent), and high positive predictive accuracy; the cut-off point was eleven millimeters or less.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229105 TI - Measurement of anterior-posterior displacement of the knee. A comparison of the results with instrumented devices and with clinical examination. AB - Thirteen subjects who had normal knees and fifteen patients who had a chronic rupture of the anterior cruciate ligament were tested in order to compare the measurements of tibiofemoral displacement as recorded by four commercial devices: the Acufex knee-signature system, the Genucom knee-analysis system, the Medmetric KT-1000 arthrometer, and the Stryker knee-laxity tester. Anterior and posterior displacement were measured at forces of eighty-nine newtons (twenty pounds) and 133 newtons (thirty pounds). We found significant differences in reproducibility of measurement among the devices. The Acufex, Medmetric, and Stryker devices had more reproducible measurements, and they could be used to identify 80 to 90 per cent of the normal subjects and anterior cruciate-deficient patients. The Genucom device had poorer reproducibility of measurement, and it tended to register greater differences in displacement between the right and left knees of normal subjects. PMID- 2229106 TI - Evaluation of an electrogoniometric instrument for measurement of laxity of the knee. AB - Eight lower extremities from cadavera were tested for anterior-posterior laxity in two positions before and after transection of the anterior cruciate ligament. At critical points in the tests, electrogoniometric and radiographic measurements of tibiofemoral translation were compared. By direct measurement, we determined the accuracy of the radiographic method to +/- 0.4 millimeter (95 per cent) in measuring anterior-posterior translations of the tibia with respect to the femur. The electrogoniometer estimated displacement of the tibia with respect to the femur during the anterior drawer test to be 3.5 +/- 8.2 millimeters at 90 degrees of flexion of the knee and 11.1 +/- 16.1 millimeters at 30 degrees of flexion. Direct comparison of these measurements with those obtained by means of the radiographic technique showed that the electrogoniometer tended, on average, to overestimate the tibial translation. The amount of overestimation was 0.7 millimeter for intact knees and 1.9 millimeters after sacrifice of the anterior cruciate ligament. Despite this small average error in measurement of tibial translation, the difference between individual electrogoniometric and radiographic measurements varied greatly, with a 95 per cent confidence limit of +/- 5.5 millimeters. The error of the electrogoniometric measurements varied with the angle of flexion of the knee during testing, both the accuracy and the reliability of the electrogoniometric measurements being greatly diminished at 30 degrees of flexion. The electrogoniometric method also tended to overestimate tibial internal rotation (by an average of 10.5 degrees) and external rotation (by an average of 9.3 degrees); the reliability of these measurements was +/- 6.9 degrees.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229107 TI - Use of a knee-brace for control of tibial translation and rotation. A comparison, in cadavera, of available models. AB - We assessed the relative restraints that are provided by fourteen currently available functional knee-braces, using six limbs in cadavera. The tests were made at 30 and 60 degrees of flexion of the knee, and a mechanical loading system applied loads that caused anterior-posterior translation and internal-external rotation. The braces limited abnormal tibiofemoral displacements by 10 to 75 per cent in translation; there was more variation in rotation. This study demonstrated that functional knee-braces provide a restraining influence that may be beneficial in the control of abnormal displacements of the knee, but that the degree of restraint varies considerably. PMID- 2229108 TI - Hypertension after operative correction of club-foot deformity. AB - Severe hypertension occurred as a postoperative complication after correction of a club-foot deformity in four children (seven feet) who were between the ages of two and three years and had no history of hypertension. The hypertension subsided slowly after administration of antihypertensive medications or more rapidly after release of the correction that had been obtained operatively. PMID- 2229109 TI - Translation of the humeral head on the glenoid with passive glenohumeral motion. AB - We have demonstrated that certain passive motions of the glenohumeral joint are reproducibly accompanied by translation of the head of the humerus on the glenoid. We investigated the relationship of these translations to the position of the glenohumeral joint and to applied torques and forces in seven isolated glenohumeral joints from fresh cadavera, using a six-degrees-of-freedom position sensor and a six-axis force and torque transducer. Reproducible and significant translation occurred in an anterior direction with glenohumeral flexion and in a posterior direction with extension. We also observed translation with cross-body movement. The translation occurring with flexion was obligate in that it could not be prevented by the application of an oppositely directed force of thirty to forty newtons. Operative tightening of the posterior portion of the capsule increased the anterior translation on flexion and cross-body movement and caused it to occur earlier in the arc of motion compared with the intact glenohumeral joint. Operative tightening of the posterior part of the capsule also resulted in significant superior translation with flexion of the glenohumeral joint. PMID- 2229110 TI - Histological studies of the glenoid labrum from fetal life to old age. AB - To help to resolve the controversy regarding the composition of the glenoid labrum, thirty-eight shoulders from cadavera were examined grossly and histologically. We used specimens for individuals of different ages so that we could determine what changes occur as a result of aging. In children and adults, the labrum appeared to be fibrocartilaginous tissue. The labrum was a separate anatomical structure that could be distinguished from the fibrous capsule of the shoulder. Neonatal labra were composed of primitive mesenchymal tissue containing only few chondrocytes that modulated into fibrocartilage in the first few years of life. Neonatal labra contained no elastin, whereas specimens from adults had rare elastin fibers. The labrum was sparsely vascularized throughout its substance, with no particular pattern of distribution. Vascularity decreased with increasing age of the individual. PMID- 2229111 TI - Comparison of a hybrid with an uncemented total hip replacement. A retrospective matched-pair study. AB - The efficacy of a type of uncemented total hip replacement was compared with that of a hybrid total hip replacement in which an uncemented acetabular and a cemented femoral component were used. Twenty-five patients who had had a hybrid total hip replacement were matched, by age, weight, sex, and diagnosis, with twenty-five patients who had had an uncemented total hip replacement. All of the operations were done by one surgeon, who used the same operative approach and the same regimen of postoperative rehabilitation. All of the patients were followed for at least two years. The mean postoperative hip score was 96 points for the hybrid group and 84 points for the cementless group (p less than 0.02). Twenty four (96 per cent) of the patients who had a hybrid prosthesis reported no or only slight pain postoperatively. In the uncemented group, of the six patients (24 per cent) who reported mild to severe pain, five had pain in the thigh, a limp occurred more frequently, five femoral components had migrated, and four hips needed reoperation. The results with the hybrid replacement that had a cemented femoral component were superior to those with the uncemented femoral component over the relatively brief period for which these patients were followed. PMID- 2229112 TI - The lateral approach for operative release of post-traumatic contracture of the elbow. AB - A lateral approach was used to release a post-traumatic contracture of the elbow in seven patients, and the results were evaluated an average of thirty-eight months postoperatively. Extension improved from an average flexion contracture of 45 degrees preoperatively to one of 12 degrees postoperatively, and the average point of maximum flexion increased from 116 degrees preoperatively to 129 degrees postoperatively. The average arc of motion increased 46 degrees. All patients began using a continuous-passive-motion device immediately after the operation. There were no problems with wound-healing or formation of heterotopic bone. PMID- 2229113 TI - Arthrodesis of the ankle with cancellous-bone screws and fibular strut graft. Biomechanical analysis. AB - The stability of an arthrodesis with two cancellous-bone screws across the ankle joint was evaluated in eighteen ankles from fresh-frozen cadavera. Tibiotalar motion was recorded in response to the following loading modes: medial-lateral moment, plantar flexion-dorsiflexion moment, and internal-external tibial torque. The series of loading tests was performed with two cancellous-bone screws through the tibia into the talus and a lateral fibular strut graft fixed with a proximal and a distal screw. The tests were repeated after the strut graft was removed, and again after it had been reapplied. The amount of motion at the site of the arthrodesis was greatest with tibial torque and was least with medial-lateral bending; this was true for specimens with or without a fibular strut graft. Removal of the strut graft allowed increased tibiotalar motion for all modes of loading; increases in motion were far greater for specimens of poor bone quality. PMID- 2229114 TI - Spondyloepiphyseal dysplasia of Maroteaux. AB - The cases of four patients who had an unusual clinical entity of disproportionately short stature, referred to as spondyloepiphyseal dysplasia of Maroteaux, are described. In patients who have this syndrome, the abnormalities are confined to the musculoskeletal system. The patients do not have corneal opacities or increased excretion of keratosulphate. The mode of transmission appears to be autosomal dominant. Platyspondylysis is present but there are no anterior tongue-like deformities of the vertebral bodies. Because of the presence of spondyloepiphyseal dysplasia and normal intelligence, and the lack of abnormalities at birth, this entity seems to mimic Morquio syndrome. However, unlike Morquio syndrome, the disorder involves no biochemical abnormalities. Thus, the entity may be classified as new. PMID- 2229115 TI - Replantation of the distal part of the leg. AB - We successfully replanted five amputated legs in five patients and followed the patients for two years or more (average, six years and three months). Although some patients found it impossible to squat and to run because of joint contractures, muscle weakness, or deformities of the foot, all patients could perform other activities without difficulty. None had important pain or any intolerance to cold, and all were satisfied with the results of the replantation. PMID- 2229116 TI - The osteogenic response to distant skeletal injury. AB - We tested the hypothesis that when one bone of the skeleton is injured, others experience an osteogenic response. Although similar or related phenomena have been observed previously, the purposes of the study were to determine if this response was reproducible, to characterize it in terms of its magnitude and duration, and to show how it is related to the type of injury sustained. To obtain this information, a model was used in which an intramedullary nail was implanted in the femur and a standard closed fracture was subsequently produced. The osteogenic response was measured by histomorphometry. Eight-four nine-week old male Sprague-Dawley rats were divided into seven groups of twelve animals each. Groups I and II consisted of control animals in which no injury was produced. In Group-III rats, cortical drilling of the intercondylar notch and piriformis fossa of the right femur was performed, without intramedullary nailing. In Groups IV through VII, half of each group received intramedullary nails only, and in the other half intramedullary nailing was done and a closed transverse diaphyseal fracture was produced. With two different fluorochrome labels, rates of mineral apposition were measured in the left and right tibiae of all animals. The labeling periods differed in each group and were designed to determine when the peak response occurred, how long it lasted, and whether aging during the course of the experiment affected the response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229117 TI - The patellofemoral joint after total knee arthroplasty without patellar resurfacing. AB - One hundred total knee replacements with a total condylar prosthesis and without patellar resurfacing were followed for a minimum of two years. Eighty-four per cent of the knees were affected by osteoarthrosis. Graded according to the knee rating system of the Hospital for Special Surgery, there were eighteen excellent, fifty-three good, eighteen fair, and eleven poor results. At the most recent follow-up, twenty-nine knees (29 per cent), nine of which were affected by rheumatoid arthritis, were still painful in the patellofemoral area. The height and weight of the patient definitely influenced the amount of patellofemoral pain postoperatively. Small patients who had osteoarthrosis were exceptionally free of pain, regardless of sex, age, or level of activity. It seems that the best approach to patellofemoral replacement includes resurfacing of the patella in all patients who have rheumatoid arthritis and in patients who have osteoarthrosis if they have preoperative patellofemoral pain, are more than 160 centimeters tall, weigh more than sixty kilograms, and have advanced changes in the patella at the time of the operation. PMID- 2229118 TI - Treatment of infection after total knee arthroplasty by debridement with retention of the components. AB - Thirty-one total knee arthroplasties were followed by infection in twenty-seven patients who were subsequently treated with debridement, retention of the components, and intravenous administration of antibiotics. The results were reviewed retrospectively in an effort to evaluate the function of the prostheses that had been salvaged successfully and to identify the causes of failure of those around which an infection had recurred. At the most recent follow-up (average duration, 8.8 years), infection had recurred around twenty-four (77 per cent) of the thirty-one arthroplasties. Seven knees (23 per cent) remained free of infection. Function remained satisfactory, although revision was subsequently needed in two knees for reasons other than infection. One cause of failure was the duration of the infection before debridement. This averaged twenty-one days for the seven knees in which the prosthetic arthroplasty had been salvaged and thirty-six days for the twenty-four knees in which treatment had failed. Another cause of failure was the type of organism: Staphylococcus aureus had caused the infection in fourteen (58 per cent) of the twenty-four knees in which the treatment failed but in only two of the seven knees in which the prosthetic arthroplasty was salvaged. In addition, eight infections in the first group were resistant to penicillin, whereas both infections in the second group were sensitive to penicillin. The four infections with gram-negative organisms in the series were all in knees in which the treatment failed. All six hinged prostheses that were used failed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229119 TI - Amputation or limb-lengthening for partial or total absence of the fibula. AB - Thirty-two patients who had ablation of the foot by the Syme or Boyd technique for partial or total absence of the fibula, with subsequent fitting of a prosthesis, were compared with eleven patients who had lengthening of the lower limb by the Wagner method, to assess the long-term results of each procedure. The final results were evaluated on the basis of pain, limp, limb-length discrepancy, level of physical activity, and satisfaction of the patient. Of the thirty-two patients who had an amputation, twenty-eight (88 per cent) had a satisfactory result, compared with only six (55 per cent) of the eleven patients who had limb lengthening. The amount of inequality between the lower limbs was classified as follows: Group I--the foot of the shorter extremity was at the distal third of the contralateral, normal limb, and the percentage of shortening was 15 per cent or less; Group II--the foot of the shorter extremity was at the level of the middle third of the contralateral, normal limb, and the percentage of shortening was between 16 and 25 per cent; and Group III--the foot of the shorter extremity was at the level of the proximal third of the contralateral, normal limb, and the percentage of shortening was greater than 26 per cent. Lengthening was best suited for patients in Group I who had stable hips, knees, and ankles and a plantigrade foot. Patients in Groups II and III were best served by ablation of the foot and fitting of a prosthesis. PMID- 2229120 TI - Total knee arthroplasty in obese patients. AB - We examined 182 patients (257 knees) who had had a total knee arthroplasty two to five six years earlier. The patients were grouped into five weight classes. Eighteen patients (twenty-seven knees) were considered moderately obese and twelve patients (twenty-seven knees), severely obese. The results in all but four knees were rated excellent or good. One patient needed a revision procedure for late infection, and the result was rated poor. Three results were rated fair. There was no discernible difference in the over-all scores among the five weight groups. However, 30 per cent of the knees of the moderately and severely obese patients had patellofemoral symptoms, whereas the incidence was 14 per cent in the other groups (p less than 0.03). No clear-cut association was found between obesity and either thrombophlebitis or complications related to the wound. PMID- 2229121 TI - Tourniquet-induced rhabdomyolysis. A case report. PMID- 2229122 TI - Non-infectious pyogenic arthritis after a blind-loop intestinal-bypass operation. A case report. PMID- 2229123 TI - Avulsion fracture of the tibial tubercle with avulsion of the patellar ligament. Report of two cases. PMID- 2229124 TI - Idiopathic osteonecrosis of the patella: an unusual cause of pain in the knee. A case report. PMID- 2229125 TI - Use of a soft-tissue cap in endoprosthetic reconstruction of the proximal part of the humerus after excision of a neoplasm. A case report. PMID- 2229126 TI - Disorders of patellofemoral alignment. PMID- 2229127 TI - Comparative assessment of gait after limb-salvage procedures. PMID- 2229128 TI - Development of a reconstituted collagen tendon prosthesis. PMID- 2229129 TI - Dietrich Schmahl on the occasion of his 65th birthday. PMID- 2229130 TI - Basic principles in preclinical cancer chemotherapy. PMID- 2229131 TI - Potentiation of cisplatin cytotoxicity by methylxanthines in vitro. AB - The ability of two supposed DNA-repair inhibitors to modulate cisplatin-induced cytotoxicity in a human ovarian cancer cell line (CAOV-3) and a human cervical cancer cell line (Me-180) was investigated using a short-term chemosensitivity assay based on bioluminescence of cellular adenosine triphosphate (ATP). Cisplatin concentrations bracketing the reported peak plasma concentration (2.5 micrograms/ml) were used and the 50% inhibitory concentrations were determined by linear regression of log-transformed survival data. At 2.5 mM, the methylxanthine caffeine enhanced cisplatin sensitivity 2.9-fold in CAOV-3 cells and 2.7-fold in Me-180 cells. At 2.5 mM, pentoxifylline, a closely related methylxanthine, increased cisplatin sensitivity 2.9-fold in CAOV-3 cells and 3.4-fold in Me-180 cells. Chemical modification of cisplatin-induced cytotoxicity by assumed inhibition of DNA-repair mechanisms may hold promise for clinical application in the treatment of gynecological cancer. PMID- 2229133 TI - D-19466, a new cyclobutane-platinum complex with antitumor activity. AB - D-19466, a new platinum complex, was characterized. It showed no nephrotoxic side effects as determined by the measurement of blood urea. It was cytotoxic in vitro for tumor cells in concentrations comparable to or lower than cytotoxic concentrations of cisplatin. It had excellent anticancer activity in vivo against a number of murine experimental tumors, including a cisplatin-resistant P388 line. Clinical evaluation of this compound has therefore been initiated. PMID- 2229132 TI - Tumor-inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes. V. Synthesis and evaluation of enantiomeric [1,2-bis-(4 fluorophenyl)ethylenediamine]dichloroplatinum(II) complexes. AB - The enantiomeric [1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) complexes were synthesized and tested on the hormone-sensitive human MCF7 breast cancer cell line and on the P388 leukemia of the mouse. They showed a strong and comparable activity on both tumor models. PMID- 2229135 TI - The pharmacokinetic model and distribution pattern of new sexual-steroid-hormone linked anticancer agents. AB - Sexual-steroid-hormone-linked anticancer agents are a new group of cytotoxic drugs designed for a site-directed chemotherapy of tumors containing sexual steroid hormone receptors. The hormone (e.g. estradiol or testosterone) should act as a carrier that leads to a preferential receptor-mediated drug accumulation in hormone-receptor-positive tumors (such as mammary carcinomas and prostatic cancer). In several preclinical therapeutic studies of sexual-hormone-receptor positive breast cancer, for instance, conjugates of 2-chloroethyl-carbamoyl-L alanine linked to estradiol or dihydrotestosterone showed, in comparison to the unlinked single agent, a significantly higher antineoplastic activity and a clearly lower systemic toxicity. But there is still only limited knowledge about the pharmacokinetic properties and the mode of action of these new drugs. For this reason in the present article a more comprehensive pharmacokinetic model and the pattern of distribution of new sexual-steroid-hormone-linked anticancer agents have been described. PMID- 2229134 TI - Sensitivity of rodent osteosarcoma clones to platinum-containing phosphonic acid complexes in vitro. AB - Osteosarcoma treatment still is unsatisfactory owing to the development of metastases. This situation causes many problems for the patients as well as the clinicians. Tumor heterogeneity is made responsible for the development of cell lines resistant to chemotherapy. As the transplantable osteosarcoma of the rat resembles the human metastasizing osteosarcoma, studies on clones of this tumor were started. The following compounds were investigated: AMDP, cis diammine[nitrilotris-(methylphosphonato)(2-)-O1,N1]plati num II; DADP, cis cyclohexane-1,2-diamine[nitrilotris(methylphosphonato)(2 -)-O1,N1]- platinum II; IMD, cis-diammine[imino-bis(methylphosphonato)(2-)-O1,N1]platinum II; DIMD, cis cyclohexane-1,2-diamine[iminobis(methylphosphonato) (2-)-O1,N1]platinum II. In vitro assays were performed with cell lines derived from a lung metastasis with the limited-dilution method. The clones varied in modal chromosome number, growth kinetics and tumorigenicity. AMDP was the most potent compound in all three clones resulting in a concentration- and time-dependent effect while IMD was somewhat less active. The diamminocyclohexane derivatives were considerably less effective, inhibiting cell growth especially in clone C10. In contrast, clone C36 was more sensitive than C25 and did not recover within the observation period of 5 days. Viability was reduced significantly only in C10, when treated with AMDP. Differences between the clones and the various compounds in inhibiting cell growth could be observed. Therefore, further experiments on the heterogeneity and sensitivity of these cell lines seem promising. PMID- 2229136 TI - Differential relationship of vitamin A and E levels in methylnitrosourea-induced Sprague-Dawley rats following prolonged feeding of fatty diets enriched with the vitamins. AB - Prolonged supplementation of vitamins A and E (2500 IU and 11.3 IU/rat daily) in 10.3% and 21.6% fatty diets administered to methylnitrosourea-induced Sprague Dawley rats caused alterations in plasma and liver levels of both vitamins as well as of the total lipids. Liver vitamin A levels increased steadily (more than fourfold) until termination of the experiment, whereas plasma vitamin A levels only showed a minor increase at the end of the study in comparison to rats fed a standard diet. Liver vitamin E levels initially showed no difference from those of rats treated with a standard diet, and were decreased at the end of the experiment, whereas the respective plasma levels were increased throughout the study, only showing a decrease relative to initial values at termination of the experiment. Plasma total lipids increased with age and following supplementation of the vitamins in the high-fat diet, whereas liver total lipids were influenced less by aging than by the fat and vitamin contents of the respective diets. The observed alterations were, however, not related to significant chemopreventive activity of the vitamins A and E contained in high-fat diets. PMID- 2229137 TI - Mutagenic and genotoxic activities of extracts derived from the cooked and raw edible mushroom Agaricus bisporus. AB - A. bisporus has been reported to be carcinogenic to mice [Toth et al. (1986) Cancer Res 38:177-180] and mutagenic in Salmonella typhimurium [Sterner et al. (1982) Mutat Res 101:269-281]. The effects of different heat treatments on the mutagenicity of raw, cooked (boiled) and fried A. bisporus extracts in the S. typhimurium test is reported. The spectrum of potential mutagenic activity of A. bisporus extracts was tested in vitro in Syrian hamster embryo cells for selective DNA amplification and in primary rat hepatocytes for DNA single-strand breaks. DNA single-strand breaks were also determined in liver cells of rats and micronuclei were measured in bone marrow cells of mice in vivo following oral application of A. bisporus extracts. It was shown that the complex A. bisporus extracts per se are not detectably mutagenic in S. typhimurium and that the previously observed increase in number of colonies per plate is probably due to a histidine artefact. No indication of genotoxicity was seen in the two in vitro assays with primary mammalian cells with two different end points. No evidence of in vivo genotoxic effects was observed in the rat liver cells. Finally, A. bisporus was not genotoxic in the micronucleus assay of mouse bone marrow cells in contrast to its previously reported carcinogenicity in mice. PMID- 2229138 TI - Assessment of nucleolar organizer regions by automatic image analysis in breast cancer: correlation with DNA content, proliferation rate, receptor status and histopathological grading. AB - The value of automatic image analysis in the investigation of nucleolus regions (AgNOR) has been examined in tissue sections of 52 malignant and 30 benign breast lesions. Determination of the AgNOR number per cell alone revealed a considerable overlap between benign (range 1.2-3.8) and malignant specimens (range 1.5-16.2). They differed however, highly significantly (P less than 0.001) in their AgNOR sizes. In benign breast disorders the mean AgNOR area per tumour ranged from 0.22 microns2 to 1.07 microns2 (mean 0.39 microns2), whereas in carcinomas AgNOR sites ranged from 0.05 microns2 to 0.22 microns2 (mean 0.09 microns2). AgNOR counts showed a good correlation with histopathological grade (P less than 0.05), aneuploidy (P less than 0.01), proliferation rate as determined by Ki67 immunostaining (P less than 0.01), as well as oestrogen and progesterone receptor content (P less than 0.01). Image analysis proved to be advantageous over AgNOR counting alone as it facilitated the standardization of the AgNOR technique itself and thus, significantly improved its diagnostic specifity. PMID- 2229139 TI - Value of bone scanning in the follow-up of breast cancer patients. A study of 1000 cases. AB - The aim of the study was to assess the value of routine bone scintigrams, independent of the primary tumor stage or the presence of symptoms, in the postsurgical follow-up of breast cancer patients for the early detection of bone metastases. For this purpose 1,000 patients with postsurgical breast cancer without previous documentation of metastatic disease, who were admitted to the special oncology hospital, Onkologische Klinik Bad Trissl, entered a prospective study in 1987-1988. The parameters followed were the TNM stage of the primary tumor, the presence of pain, bone pain as revealed by a thorough physical examination, and the patient's history for the assessment of risk factors. In addition, a whole-body skeletal scintigram, supplementary X-rays, and additional diagnostic measures were performed, if necessary, to detect bone metastases. It was shown that in 856 of 894 patients (groups 1-6) without clinical symptoms, the clinical examination and radiological and scintigraphic diagnostic measurements, demonstrating the absence of bone metastases, gave matching results, but in 12 of the 894 patients the results of all examinations remained questionable. In another 12 of the 894 patients (groups 1-3) radiological and/or scintigraphical evidence for the presence of bone metastases was found. In 14 of 79 cases (groups 7-10) with clinically suspicious symptoms these were proven to be signs of metastases by subsequent scintigrams, supplementary X-rays, and additional diagnostic measures. In 65 of the 79 patients with clinically suspicious symptoms, bone metastases could not be confirmed by obtaining bone scintigrams or X-rays while in the other 14 patients (groups 9 and 10) evidence for the presence of bone metastases was found in the scintigrams and/or X-rays. However, 10 of these 14 patients were high-risk patients for developing bone metastases as they had axillary lymph node infiltration. The other 4 patients were of the low-risk group as they had positive receptor status or no axillary lymph node infiltration at the time of primary diagnosis. In 13 of 27 patients (groups 11-14) with clinical symptoms indicating the presence of bone metastases this diagnosis was confirmed by scintigrams and/or X-rays (groups 11 and 12), while it was possible to exclude the presence of bone metastases in spite of the symptoms in 11 of the 27 patients. In the other 3 patients the results of the additional examinations remained questionable.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2229141 TI - The mutagenic activity of human breast secretions. AB - Human breast secretions, as obtained by nipple aspiration, were analysed for the presence of mutagenic activity by means of the Ames test. The overall incidence of women with secretions giving positive tests against Salmonella typhimurium, either strain TA98 or TA100, was 7.64%. No significant association was identified between the incidence of mutagen-positive breast secretions and age, menopausal status or the presence of breast abnormality in these women. Furthermore, there was no obvious environmental characteristic common to women with mutagen-positive fluids. PMID- 2229140 TI - Down-regulation of androgen receptor by progestins and interference with estrogenic or androgenic stimulation of mammary carcinoma cell growth. AB - The regulatory influence of medroxyprogesterone acetate (MPA) on estrogen and androgen receptors of the human breast cancer cell lines MCF-7 and EFM-19 was explored in conjunction with the growth-promoting properties of these steroids. In the absence of steroidal stimulation, up to 1 microM MPA had no effect on the proliferation of the MCF-7 cell strain used and of EFM-19 cells. Under stimulation with 10 nM 17 beta-estradiol or 1 microM dihydrotestosterone, dose dependent inhibition of the cell proliferation rates by 0.1-1 microM MPA was observed. Binding of MPA to the androgen receptor (Kd = 2.1 nM) but not to the estrogen receptor was demonstrable. During incubation of MCF-7 or EFM-19 cells with 1 microM MPA for 7 days, the estrogen and androgen receptor contents were down-regulated by approximately 50% and 60%, respectively. Likewise, the number of androgen-binding sites was reduced to 35% of the untreated controls after incubation of MCF-7 cells with 1 microM synthetic progestin R5020 for 7 days. The results indicate down-regulation of estrogen and androgen receptors by progestins in the absence of stimulatory effects on the proliferation of mammary carcinoma cells. PMID- 2229142 TI - Phase II study of tamoxifen and high-dose retinyl acetate in patients with advanced breast cancer. AB - Retinoids have shown a tumor growth inhibition and a synergistic activity with hormonal manipulations in human breast cancer cell lines and rat mammary carcinoma. To investigate the potential usefulness of this synergistic activity in human breast cancer, 33 postmenopausal patients with advanced disease were treated with the combination of tamoxifen (10 mg p.o. three times a day) and retinyl acetate (300,000 IU p.o. daily). Out of 31 evaluable patients, 3 achieved complete response, 9 partial response (overall response rate: 38.5%, 95% confidence interval = 21%-56%) and 16 (52%) showed no change. The median duration of response was 11.5 months (range: 3-19+ months), while the 2-year overall survival rate for the entire group of patients was 63%. Toxicity was generally mild, hot flushes, nausea (and/or vomiting), headache and cutaneous itching being the most frequent side-effects. Only 1 patient discontinued treatment for severe toxicity. These preliminary results suggest that the combination of tamoxifen and high-dose retinyl acetate is a safe and effective regimen for breast cancer patients. However, the study design does not allow us to establish whether the very low rate of early disease progression we observed might be related to a possible synergistic effect between retinoids and antiestrogens or rather to the quite indolent disease of the patients who have been selected for entry into this trial. PMID- 2229143 TI - Prognostic grouping: the next step in tumor classification. AB - At present, staging of malignant tumors is based on the anatomical extent of disease defined by the T(umor) N(odes) M(etastasis) classification. The main objective of further efforts in classifying tumors is to identify additional independent prognostic factors and to create mathematical models that may predict disease progression by prognostic grouping. This article summarizes problems, methods and the design of coordinated studies on prognostic grouping. PMID- 2229144 TI - The vascular architecture of human xenotransplanted tumors: histological, morphometrical, and ultrastructural studies. AB - This study was designed to examine the vascular system of human xenotransplanted tumors on nude mice with different complementary morphometrical and morphological methods. The vascular system shows a chaotic arrangement. There is an extreme heterogeneity in the vascular distribution and density. Large avascular regions could be identified in several non-necrotic tumors. There was no clear difference in the vascular density between the center and the periphery of the tumors, nor was there any zonal correlation for the distribution of the necrosis. With three dimensional corrosion casts it could be demonstrated that clusters of vessels were directly beneath areas almost free of vessels. In the center, vessels often form a sinusoidal system with numerous blind ends without clearly discernible endothelial cells. Numerous irregular tumor-cell-lined sinusoids are visible next to endothelial-lined vessels with transmission electron microscopy. With scanning electron microscopy it could be demonstrated that large-calibre endotheliazed vessels were found in the direct vicinity or in the center of non-viable zones. Even large-calibre vessels have a capillary wall structure. Sometimes, a basement membrane cannot be observed at all or only incompletely. There are numerous indications of vascular discontinuities and leaks with a widespread intercellular occurrence of blood cells. PMID- 2229145 TI - Histocompatibility locus antigens (HLA) in the epidermoid type of lung carcinoma. AB - HLA-A and B antigens were determined in a study of 162 patients (93 epidermoid type, 20 adenocarcinoma, 26 small-cell carcinoma and 23 undifferentiated types) with lung cancer. Differences between antigen frequencies in cancer and control populations were studied by chi 2Y analysis or Fisher's exact test. Survival data were analyzed using Cox's model for censored data. Cancer patients had a decreased frequency of the antigen HLA-B40 (chi 2Y = 14.15, P = 0.00018, Pc = 0.003, relative risk = 0.21). Patients with HLA-A10, A 11 and B27 had a shortened mean survival time. Patients with HLA-B12 had a prolonged survival time. PMID- 2229146 TI - Recent advance in treatment of Stanford type A aortic dissection. AB - During the period between November 1986 and November 1988, 13 consecutive patients with Stanford type A aortic dissection (8 acute and 5 chronic) were treated as follows: (1) urgent operation for cases with pericardial tamponade or severe heart failure, (2) initial medical treatment followed by elective operation for acute but stable cases or chronic cases, and (3) routine use of open distal anastomosis or selective cerebral perfusion. One patient died during medical treatment: 5 patients were operated on emergently. The remaining 2 acute and 5 chronic cases were operated on electively. There were no operative deaths, neurological disturbances, or late deaths. It is suggested that acute dissection of the ascending aorta requires immediate surgical intervention, especially when the entry is in the ascending aorta. On the other hand, it is also suggested that one could avoid emergency operations in selected cases with retrograde extension of the aortic dissection. PMID- 2229147 TI - Surgical treatment of aneurysm or dissection involving the ascending aorta and aortic arch, utilizing circulatory arrest and retrograde cerebral perfusion. AB - Recently we replaced the ascending aorta and aortic arch in 8 patients with aneurysm or dissection, using profound hypothermic circulatory arrest with retrograde cerebral perfusion. There were no operative deaths. Open aortic anastomosis facilitated repair of the aortic arch without clamping the arch tributaries, and embolism due to particulate debris from clamping of the arch vessels was eliminated. Retrograde cerebral perfusion during profound hypothermic circulatory arrest is a simplified technique that may protect the brain. This method offers advantages over previously described methods, particularly in obviating dissection of the arch tributaries and the clamping thereof, and in protecting the central nervous system. PMID- 2229148 TI - Aggressive blood conservation in coronary artery surgery: impact on patient care. AB - Data on 100 consecutive non-emergency coronary artery bypass (CABG) patients were analyzed retrospectively. Sixty-nine patients received no homologous blood (Group I). Thirty-one patients received a total of 118 units of blood products averaging 2.23 units of red cells (Group II). The average red cell transfusion rate for all patients was 0.7 units per patient. The median age for Group I was 61 and Group II was 68 years (p less than 0.05). The average number of grafts was the same for both (3 per patient) with 75% of Group I and 58% of Group II receiving internal mammary artery (IMA) grafts (p less than 0.05). Twelve of the Group II patients who received intraoperative transfusions on cardiopulmonary bypass to maintain adequate hemoglobin levels were older and had lower admission hematocrits: 36 +/- 0.8% compared to 41 +/- 0.5% for all other patients (p less than 0.05). Average postoperative blood loss was 889 +/- 38 ml for Group I and 1077 +/- 104 ml for Group II (p less than 0.05). Increased hemorrhage was correlated with bypass time and IMA use but not with preoperative heparin administration, pre-existing risk factors (diabetes, hypertension, etc.), bleeding time, post-bypass clotting time, age or number of grafts. Two patients in Group II and none in Group I required exploration for excessive postoperative hemorrhage. Mortality rate was 2% (both in Group II, neither transfusion related). Discharge hematocrits were the same for all at 29.4 +/- 0.4%. Among anemia-related postoperative symptoms, only sinus tachycardia was significantly higher in Group I (20%) compared to Group II (6.5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229149 TI - Efficacy of transesophageal echocardiography as a perioperative monitor in patients undergoing cardiovascular surgery. Analysis of 149 consecutive studies. AB - To evaluate the usefulness of transesophageal echocardiography as a perioperative monitor in patients undergoing cardiovascular surgery, 149 consecutive patients were studied since 1985. Left ventricular function was assessed by measurement of left ventricular dimension and ejection fraction in patients with valvular disease. This monitoring was useful in detecting the changes in left ventricular performance in patients with volume overload and in managing patients in the early postoperative period. Cardiac tamponade was clearly demonstrated before changes in electrocardiogram and hemodynamic data. In 27 patients, transesophageal color Doppler echocardiography was used to confirm that there was no residual regurgitation immediately after valvular reconstructive surgery. Transesophageal color Doppler echocardiography was also useful in detecting the entry of false lumen before surgery in 7 patients with dissecting aortic aneurysm. There were no unsuccessful introductions, no traumatic or thermal injuries, 18 patients (12.1%) with hoarseness and 5 patients (3.4%) with transient arrhythmia. In conclusion, transesophageal echocardiography provides a good imaging window to the heart and great vessels perioperatively. This expedient, safe informative imaging method can be used more routinely in patients during surgery. PMID- 2229150 TI - Measurement of resistance versus flow in assessing efficiency of aortocoronary bypass grafts. AB - Measurement of flow in saphenous bypass grafts with an electromagnetic flowmeter is complicated and poorly reproducible. Since coronary flow is largely dependent on variable factors the stable value of resistance seems more appropriate for comparison. A simple method has been developed for intraoperative measurement of resistance in the respective coronary bed. Pressure is recorded in the saphenous graft by an electromanometer during continuous flushing with known amounts of blood, and resistance is calculated instantaneously. The procedure is very simple and takes less than one minute. The quality of the saphenous vein itself can be assessed simultaneously by the same method. Resistances were measured during coronary surgery in over 500 saphenous grafts. The results were highly reproducible and comparable. Excellent flows can be expected if resistance is below 200 Peripheral Resistance Units (PRU); if this is over 800 PRU flow is very poor. PMID- 2229151 TI - Submammary median sternotomy. AB - A vertical skin incision is used as routine approach for sternotomy. The resulting scar is often disappointing and the top is visible and unpleasant, especially for young women. In 35 women ranging from 10 to 48 years (mean 29.2 years), median sternotomy was performed via a submammary skin incision. In all cases an open heart surgical procedure was performed. Adequate exposure of the heart was achieved in every case and there were no technical problems related to this approach, no hospital mortality or major complications. The cosmetic result is excellent and this approach is certainly justified in open heart surgery for young women. PMID- 2229152 TI - Valvular and coronary surgery in renal transplant patients. AB - The Authors report aortic valvular replacement (AVR) and coronary artery bypass graft surgery (CABG) successfully performed in two renal transplant patients. The postoperative blood urea and creatinine levels were comparable to the preoperative values. The first patient underwent isolated AVR. The second patient had an initial AVR combined with CABG followed two years later by a further AVR for prosthetic dysfunction. For many reasons, coronary artery (CAD) and valvular diseases are not uncommon in renal transplant patients. Cardiac surgery is feasible without impairment of the renal function provided some precautions are taken, ie good mean perfusion pressure during cardiopulmonary bypass (CPB), adequate volume replacement, and selected use of mannitol and dopamine. PMID- 2229153 TI - Successful surgical treatment of subaortic stenosis caused by an accessory mitral valve. AB - A 22-month-old boy with subaortic stenosis was found to have relatively mature mitral valve tissue beneath the aortic valve, associated with a hypertrophic and prominent interventricular septum. This tissue caused obstruction of the left ventricular outflow tract and resulted in a pressure gradient of 70 mmHg between the aorta and the left ventricle. Surgical treatment was successfully performed to excise the tissue and part of the hypertrophic ventricular septum. Results of microscopic examination of the resected specimen are shown and discussed. PMID- 2229154 TI - An unusual late complication following surgical repair of tetralogy of Fallot. AB - A case is presented of extrusion of right ventricular outflow tract patch material through a mediastino-cutaneous fistula occurring five years after repair of tetralogy of Fallot. The focus of the mediastinal infection was an infected epicardial pacemaker electrode placed at the time of initial surgery. Subsequent echocardiographic studies showed minimal right ventricular outflow tract or pulmonary arterial dilatation, and, with no further surgery, the child is well after two and a half years follow-up. PMID- 2229155 TI - Acute dissection of the internal mammary artery: a fatal complication of coronary artery bypass grafting. AB - A case of acute traumatic dissection of the right internal mammary artery is presented in a patient who had both IMAs grafted for recurrent angina 10 years after initial vein coronary revascularisation. The event was mistaken for spasm, but because of severe circulatory collapse no time was available to treat the patient appropriately. The purpose of this report is to facilitate the early recognition and avoidance of this potentially fatal complication. PMID- 2229156 TI - Traction injury in the internal mammary artery. Report of a case and review of the literature. AB - The internal mammary artery (IMA) is now used routinely along with saphenous vein for myocardial revascularization procedures. We have documented a particular form of non-perforating injury which may reduce blood flow during operation or may lead to early closure of the IMA bypass graft. Traction injury to the intima is well documented in other vessles but has not been previously reported in the IMA. We present a potentially disastrous example of traction injury to the IMA. PMID- 2229157 TI - Three staged approach to the surgical management of renal cell carcinoma extending into the right atrium. Case report. AB - Left renal cell carcinoma extending into the right atrium was treated by angioinfarction, removal of right atrial tumour using cardiopulmonary bypass and ten days later abdominal radical nephrectomy and inferior vena cava thrombectomy. Twenty four months later the patient remains well with no evidence of tumour recurrence. PMID- 2229158 TI - Intraoperative assessment of cerebral ischemia during carotid surgery. AB - One of the problems in carotid surgery is the intraoperative detection of brain ischemia. None of the methods (EEG; stump pressure) applied so far have been successful. Branston et al. (1974) found a threshold relationship between cortical cerebral blood flow and cortical somatosensory evoked potential (SEP). As the local blood flow fell below about 16 ml/100 g/min a progressive reduction occurred in the amplitude of the cortical evoked potential (N20/P25), implying a fundamental failure of neuronal function in the somatosensory cortex. We have monitored cortical SEP (somatosensory evoked potential) during 734 CEA's (carotid endarterectomies) in order to find an index of risk of incipient cerebral ischemia during carotid cross-clamping, to determine the need for shunting and the causes of early irreversible neurologic deficits. In 59 cases evaluation of SEP was not possible because of technical difficulties. During 586 CEA's no alteration of SEP occurred. However, 4 patients had an immediate postoperative neurologic deficit, while the SEP remained normal. Abnormal SEP occurred in 89 cases and in 6 of these an irreversible loss of SEP was seen. These patients awoke with a new neurologic deficit. We found a reversible abnormal SEP in 83 cases. Reversible changes of SEP occurred mainly during carotid clamping. The diagnostic sensitivity of intraoperative SEP monitoring in predicting neurologic outcome was 60% with a specificity of 100%. PMID- 2229159 TI - Reappraisal of surgical treatment of traumatic transection of the thoracic aorta. AB - Since Crawford's report in 1973, repair of traumatic transection of the thoracic aorta without shunt or bypass has emerged as a popular technique which simplifies the operation and avoids use of heparin. Growing evidence, however, indicates that the incidence of paraplegia is higher with this method and may outweigh its advantages. With this in mind, we have examined our experience with 40 patients who underwent repair of aortic transection from 1975-1988. The operated patients in our series all survived. Fourteen were repaired using some type of bypass or shunt, none of whom developed paraplegia. The remaining 26 patients were repaired without a shunt and 9 (34.6%) developed paraplegia or paraparesis (p less than 0.02). Paraplegia was related to aortic occlusion time (p less than 0.002). It did not occur in 11 patients with times less than 27 minutes, but happened in 2 of 8 patients with times between 28 and 35 minutes and in all 7 patients with clamp times over 35 minutes. These data suggest that shunt or bypass should be used in most cases of aortic transection. PMID- 2229160 TI - Inflammatory abdominal aortic aneurysms. AB - In a series of 517 operations for abdominal aortic aneurysm from 1971 to 1988 there were 45 cases (8.7%) with an inflammatory aneurysm with a typical thick glistening whitish fibrous layer. Almost two-third of the patients had rather severe chronic or acute progressive pain in the abdomen, the back or the flank. Unilateral (7) or bilateral (2) hydronephrosis due to ureteral compression occurred in 9 patients (20%). A diagnosis of inflammatory aneurysm was made preoperatively only in 10 patients. In 8 of the 9 patients with hydronephrosis ureterolysis was done, unilaterally (6) or bilaterally (2). After ureterolysis all had complete resolution of the hydronephrosis. Preoperative diagnostic methods are excretory urography, showing medial deviation, ultrasonography and CT scanning of the abdominal aorta. All patients with an inflammatory aneurysm should undergo aortic replacement to prevent rupture and achieve pain relief. Ureterolysis in cases of hydronephrosis is strongly recommended and may be performed safely and with excellent results. PMID- 2229161 TI - Thrombectomy for late graft limb occlusion: our experience in 182 consecutive cases. AB - Late occlusion of an aortofemoral bypass graft is usually caused by fibrointimal hyperplasia or progressive atherosclerosis. Several surgical approaches have been advocated in order to minimize the operative risk, to correct the impaired inflow and to provide a satisfactory outflow. In the last 16 years, in the Institute of Vascular Surgery and Angiology of the University of Milan, we have operated upon 182 consecutive thrombosed grafts. Inflow was restored by performing a graft limb thrombectomy using a Fogarty balloon catheter and simultaneously employing an endarterectomy ring stripper to dislodge tenaciously adherent fibrinous material and thrombotic plug. As the superficial femoral artery was generally occluded, usually a good outflow was achieved by profundaplasty in 101 cases (55.5%) or direct bypass (interposition graft), to a more distal segment of the profunda femoris artery in 55 cases (30.2%). Concomitant popliteal or tibial revascularization was done in the remaining 26 cases (14.3%) when pre-operative or intra-operative findings suggested an inadequate collateral network through the profunda femoris artery. Early re-occlusion, which occurred in 14 cases (7.6%), generally due to insufficient outflow, was corrected by additional intervention in 7 cases (3.8%), while 7 legs were amputated for extensive atherosclerotic disease. Six patients died giving a mortality rate of 3.3%. This low rate in a high risk population is probably related to our policy of operating under loco-regional anaesthesia. Long term results, with a patency rate of 62.0% at 3 years and 60.2% at 5 years (life table method), prove that this operation is a durable procedure for correction of graft limb thrombosis. PMID- 2229162 TI - Assessment of major venous anomalies by computerized tomography. AB - Congenital anomalies of major venous structures are not common but their identification and relative position, particularly in relation to an abdominal aortic aneurysm, are of significant value in planning and conducting aortic operations. Computed tomography (CT) has become a common method of preoperative evaluation of aortic disease. Its reliability in providing accurate information regarding aneurysmal size, configuration, and extension, as well as the presence of intraluminal thrombus and involvement of the renal and iliac arteries, has been demonstrated. Simultaneous visualization of the major adjacent venous structures with the use of contrast enhancement is obtained, but anatomic variants can be overlooked because they are commonly subtle and considered incidental. The preoperative diagnosis of these venous abnormalities is significant to the vascular surgeon. Such information can be accurately and reliably acquired with the present CT techniques without the need for further diagnostic studies. PMID- 2229163 TI - Left retroperitoneal exposure for distal mesenteric artery repair. AB - Distal disease in the mesenteric arteries has usually been repaired transabdominally since it is believed that only the proximal centimeter of each vessel is accessible through the retroperitoneum. We treated five patients with chronic visceral ischemia and lesions extending beyond the orifice using a retroperitoneal approach. Exposure was obtained with a left flank incision through the tenth interspace. The left crus of the diaphragm was divided in order to control the supraceliac aorta. The mesenteric vessels were identified and dissected until their entrance into the peritoneum. There were no difficulties in exposing the superior mesenteric artery (SMA) as it coursed under the pancreas and over the duodenum for an approximate length of 5 to 10 cm. The uncinate process of the pancreas was not a limiting factor for exposure of the SMA in this region and further distal exposure could be obtained by incising the peritoneum. The trifurcation of the celiac artery and the splenic artery were accessible through this exposure; however, only the first centimeter of the hepatic and gastric branches could be reached. Revascularization was performed with endarterectomy (2 patients) and bypass (3 patients). Bowel viability was assessed at the conclusion of the procedure by incising the peritoneum. There were no complications from this exposure and no patient required reoperation for ischemic bowel. We conclude that the left retroperitoneal approach is not only acceptable for orifice lesions but is also applicable for distal disease. PMID- 2229164 TI - Stimulation of adenylate cyclase activity in cultured endothelial cells subjected to cyclic stretch. AB - While vascular endothelial cells are repeatedly stretched by the pulsatile nature of cardiac output, in vitro models traditionally used to study vascular biology involve static culture techniques. We have recently shown that pulsatile stretching of endothelial cells in culture will increase their rates of proliferation and regulate their secretion of macromolecules. The aim of this study was to determine whether membrane adenylate cyclase is involved in intracellular signalling during pulsatile stress. Bovine aortic endothelial cells were seeded on flexible-bottomed culture wells (3 x 10(5) cells/25 mm well) and allowed to attach for 48 hours. The culture wells were placed in a vacuum operated stress providing instrument and subjected to 0.5 s of 24% strain, 0.5 s relaxation (60 cycles/min) for 0, 1, 3, 5, 7, 10 and 15 minutes (N = 24 wells/time point). Cells were homogenized and a crude membrane preparation (27,000 x g) was assayed for adenylate cyclase under basal and forskolin (100 microM) stimulated conditions. The results indicate that there is a time dependent increase in both basal and stimulated adenylate cyclase with cyclic deformation and suggest that there may be a "stretch receptor" coupled to adenylate cyclase which can modulate endothelial cell function with hemodynamic changes. PMID- 2229165 TI - The effect of adjunctive arteriovenous fistula on prosthetic graft patency: a controlled study in a canine model. AB - Bilateral 6 mm PTFE grafts were placed from the external iliac artery to the femoral artery with ligation of the intervening segment of the iliofemoral artery in 14 dogs. An arteriovenous fistula was constructed at the distal anastomosis on one randomly selected side in each animal while the contralateral graft served as a control. Graft follow-up ranged between 8 and 12 months in all animals. Serial arteriography was performed to confirm graft and fistula patency and demonstrated persistence of antegrade flow into the arterial tree distal to all patent bypasses. Femoral intraarterial pressures distal to patent grafts were identical on both sides in each animal throughout the study. Cumulative life-table patency rates showed higher patency for the arteriovenous fistula bypasses than the control grafts at all time intervals: 71% vs. 57% at 3 months, 48% vs. 25% at 6 months, and 40% vs. 22% at 12 months, respectively. This is the first controlled study that provides experimental evidence suggesting that these bypasses may produce increased patency of prosthetic arterial grafts and lends support to their use in a clinical, prospective, randomized study. PMID- 2229166 TI - Effect of antiplatelet and anticoagulant therapy on patency of femorotibial bypass grafts. AB - In a retrospective study, 210 autogenous femorotibial saphenous vein grafts inserted during the 15 years from 1967 to 1982 were followed-up for a mean period of 62.3 +/- 5.7 months. Seven patients, who had had eight grafts died in hospital. The remaining 202 grafts fell into three groups: (1) Sixty grafts in patients who received 325 mg of dipyridamole and 1.0 g of acetylsalicylic acid daily, starting on the second postoperative day and continuing for six months. (2) One hundred and two grafts in patients on no antithrombotic therapy. (3) Forty grafts in patients on warfarin therapy to maintain the prothrombin time (prothrombin-proconvertin method) within the therapeutic range (0.10 to 0.20). Medication was continued for six months. This group included more high-risk patients than the other two groups. The mean ages and the incidence of risk factors did not vary significantly between the groups. The patency rates in three groups at five years were 62.5%, 44.0% and 26.0% and at ten years 48.5%, 25.0% and 21.5% for the dipyridamole and acetylsalicylic acid, no therapy and warfarin groups, respectively. The limb salvage rates were 100%, 96% and 85% in the dipyridamole and acetylsalicylic acid, no therapy and warfarin groups respectively. Thus, the best results were seen in the aspirin/dipyridamole group. PMID- 2229167 TI - Balloon dilatation versus surgical revision of infra-inguinal autogenous vein graft stenoses: long-term follow-up. AB - Although infra-inguinal autogenous vein graft stenoses may be treated by balloon dilatation (PTA) or surgical revision, the optimal approach is undefined. Over the last 7 years 24 PTA procedures were performed on 37 vein graft stenoses in 19 grafts. Graft stenoses were diagnosed from 2 to 72 (mean = 17.3) months after implantation. PTA was successfully completed in 23 (96%) of the 24 procedures including 18 (95%) of the primary, and 5 (100%) of the secondary procedures. Recurrent vein graft stenosis or graft thrombosis developed in 12 (67%) grafts from 3 to 47 (mean = 12.5) months after primary PTA. Long-term patency after primary PTA was 69% at 6, 29% at 12, and 22% at 36 months; secondary patency was 81% at 6, 45% at 12, and 27% at 36 months. During the same period vein graft stenosis in 7 fem-pop and 2 fem-tib grafts were surgically revised with an initial success rate of 100%, and 2 (22%) complications. Four (44%) of these grafts occluded from 1-17 (mean 6.2) months after repair, yielding a primary 5 year patency of 62%. Although vein graft stenosis may be safely, effectively, and repeatedly treated with PTA, long-term durability appears to be superior after surgical revision. PMID- 2229168 TI - Surveillance of in situ infrainguinal bypass grafts: conventional vs. color flow duplex ultrasonography. AB - Surveillance of in situ saphenous vein bypass grafts with duplex scanning detects graft abnormalities which may lead to graft thrombosis. Correction of these defects, while grafts are still patent, potentially improves overall graft patency. In this study we compared color flow and conventional duplex to determine whether color flow provided additional information not obtainable by conventional duplex examination. The primary patency rate (patency maintained without intervention) for all 51 cases was 76% (39/51). The secondary patency rate (patency maintained by identification and correction of graft defects before failure) was 88% (45/51). Duplex scanning reduced the graft failure rate by 50%. Color flow and conventional duplex examination provided the same information regarding incipient graft failure. In 20 patients monitored with both techniques, the same number of proximal (100%) and distal (90%) anastomoses were imaged. The same number of graft defects (three vein graft stenoses, one proximal femoral artery stenosis) were identified. Velocity data obtained using the two techniques (peak systolic velocity in an area of stenosis and the duplex velocity ratio) were not always the same, making calculation of percent stenosis from this data inaccurate. Color flow duplex is useful in monitoring graft patency, but provides no additional information over that provided by conventional scanning. PMID- 2229169 TI - Aneurysmal dilatation in saphenous vein bypass grafts. AB - Three patients are reported who developed aneurysmal degeneration of a saphenous vein arterial bypass graft. All three had hypercholesterolemia and two had marked elevation of triglycerides. One bypass was for occlusive disease and two for popliteal aneurysm. There was a long lag, 3 to 7 years between graft implantation and aneurysmal degeneration. The pathology was similar for all three cases with lipid laden macrophages, loss of elastic lamina, and other atherosclerotic changes in the vein wall. While atheromatous changes and aneurysm formation in saphenous vein bypass grafts are rare, this may occur especially in patients with hypercholesterolemia and hypertriglyceridemia. Careful and prolonged follow-up plus vigorous management of the hyperlipidemic state is mandatory in these patients. PMID- 2229170 TI - Primary varicose veins: topographic and hemodynamic correlations. AB - This study was conducted to correlate the clinical presentations of uncomplicated primary varicose veins with the topographic and anatomic source of reflux (escape points). One-hundred sixty-three patients with primary varicose veins (144 females, 19 males; 96 unilateral, 67 bilateral) in 230 involved limbs were examined. The origin and extent of venous reflux was traced with Doppler ultrasound. Three distinct groups were recognized. Group I. Typical saphenous varicosities with junctional escapes occurred in 164 (71.3%). Sapheno-femoral junction (SFJ) incompetence in 147, and sapheno-popliteal junction (SPJ) incompetence in 17 limbs. Group II. Atypical saphenous varicosities with non junctional escapes occurred in 51 (22.17%) limbs. In 5 limbs, no escape was detected. Twenty-two limbs had escapes localized in the main perforators: mid thigh perforator 17, upper calf 2, distal ankle in 3. Twenty-four limbs had their escapes in the auxiliary perforators: abdomino-pelvic 17, and circumflex iliac/external epigastric, 7 limbs. Group III. Non saphenous (lateral venous system) varicosities occurred in 15 (6.52%) limbs. Based on physical examination alone, 55 limbs would possibly have undergone unnecessary ankle to groin stripping and 83 limbs an unnecessary SFJ ligation. Doppler US is an essential diagnostic tool that can accurately map the origin and extent of the venous reflux. The obtained hemodynamic information will permit more selective, multimodal therapy and avoid the indiscriminate, often unnecessary stripping of the entire saphenous system in all cases of primary varicose veins. PMID- 2229171 TI - Management of deep venous thrombosis in the pregnant female. AB - Deep venous thrombosis of the lower extremities is an uncommon but dreaded complication of pregnancy which can present diagnostic and therapeutic problems to the treating physician. From January 1, 1985, to December 31, 1988, 7867 deliveries were performed at St. Luke's Hospital. Five of these patients were pregnant women who were treated for deep venous thrombosis of the lower extremities. The women were either in their second or third trimester of pregnancy. The clinical diagnosis in each case was confirmed with duplex ultrasonography. Each patient was treated with 7 to 10 days of intravenous heparin therapy and then discharged on subcutaneous heparin therapy. There were no bleeding complications related to the heparin therapy. No patient developed a pulmonary embolism. Each patient delivered a normal child. The only complication was a heparin induced rash in one patient which resolved when a different preparation of heparin was used. The management of deep venous thrombosis in pregnancy is discussed. PMID- 2229172 TI - Multifunctional Ca2+/calmodulin-dependent protein kinase is necessary for nuclear envelope breakdown. AB - The role of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase) in nuclear envelope breakdown (NEB) was investigated in sea urchin eggs. The eggs contain a 56-kD polypeptide which appears to be a homologue of neuronal CaM kinase. For example, it undergoes Ca2+/calmodulin-dependent autophosphorylation that converts it to a Ca2(+)-independent species, a hallmark of multifunctional CaM kinase. It is homologous to the alpha subunit of rat brain CaM kinase. Autophosphorylation and substrate phosphorylation by the sea urchin egg kinase are inhibited in vitro by CaMK(273-302), a synthetic peptide corresponding to the autoinhibitory domain of the neuronal CaM kinase. This peptide inhibited NEB when microinjected into sea urchin eggs. Only one mAb to the neuronal enzyme immunoprecipitated the 56-kD polypeptide. Only this antibody blocked or significantly delayed NEB when microinjected into sea urchin eggs. These results suggest that sea urchin eggs contain multifunctional CaM kinase, and that this enzyme is involved in the control of NEB during mitotic division. PMID- 2229173 TI - Identification of two HSP70-related Xenopus oocyte proteins that are capable of recycling across the nuclear envelope. AB - Two 70-kD polypeptides, B3 and B4, are present in equivalent concentrations in the nucleus and cytoplasm of Xenopus oocytes. The objectives of this study were to determine if they (a) are members of the 70-kD family of heat shock proteins, and (b) recycle between the nuclear and cytoplasmic compartments. Evidence based on high-affinity binding to ATP, cross-reactivity of B3/B4-specific antibodies with rat hsc70, and a comparison of cyanogen bromide cleavage peptide maps with hsc70, verified that B3 and B4 are members of the 70-kD family of heat-shock proteins. Nuclear uptake studies were performed by microinjecting 125I-labeled B3/B4, rat hsc70, and BSA into the cytoplasm of oocytes, and examining their subsequent intracellular distributions. By 6 h postinjection, the nuclear concentration of B3/B4 and hsc70 were approximately 24-fold greater than BSA controls. It was also found that B3/B4-coated gold particles as large as 120A in diameter were able to enter the nucleus by passing through the pores. Nuclear efflux was analyzed by microinjecting the iodinated proteins directly into the oocyte nuclei. 2 h after nuclear injection, at least 46% of the B3/B4 and 60% of the hsc70 were found in the cytoplasmic fractions, compared with less than 10% for the BSA controls. Cell fusion experiments, in which labeled, anucleate oocyte vegetal hemispheres were fused, under oil, with nucleate unlabeled animal hemispheres, demonstrated that cytoplasmic B3 and B4 could enter the nucleus after equilibration was reached, arguing against the existence of separate nuclear and cytoplasmic populations. Collectively, these results show that B3, B4, and rat hsc70 are transported across the nuclear envelope and recycle between the nucleus and cytoplasm. PMID- 2229174 TI - Characterization and inducibility of hsp 70 proteins in the male mouse germ line. AB - The properties and inducibility of the heat shock protein 70 (hsp 70) gene products were examined during differentiation of mouse testicular cells by one and two-dimensional gel electrophoresis and immunoblotting. Low levels of the 72- and 73-kD heat shock proteins normally found in mouse cell lines were detected in the mouse testis. A novel isoform with a relative molecular mass of 73 kD (called 73T) was also observed, in the presence or absence of heat shock. 73T was shown to be produced by germ cells since it was not detected in testes from mutant mice devoid of germ cells. Furthermore, 73T was found only in adult mouse testicular cells, not in testes from animals that lack meiotic germ cells. 73T was synthesized in enriched cell populations of both meiotic prophase and postmeiotic cells, but was not inducible by in vitro heat shock. In the adult testis, low levels of the bona fide 72-kD heat-inducible (hsp72) were induced in response to elevated temperatures. In contrast, in testes from animals in which only somatic cells and premeiotic germ cells were present, there was a substantial induction of hsp 72. It is suggested that hsp 72 is inducible in the somatic compartment and possibly in the premeiotic germ cells, but not in germ cells which have entered meiosis and which are expressing members of the hsp 70 gene family in a developmentally regulated fashion. PMID- 2229175 TI - Evidence that proteolysis of the surface is an initial step in the mechanism of formation of sperm cell surface domains. AB - On terminally differentiated sperm cells, surface proteins are segregated into distinct surface domains that include the anterior and posterior head domains. We have analyzed the formation of the anterior and posterior head domains of guinea pig sperm in terms of both the timing of protein localization and the mechanism(s) responsible. On testicular sperm, the surface proteins PH-20, PH-30 and AH-50 were found to be present on the whole cell (PH-20) or whole head surface (PH-30, AH-50). On sperm that have completed differentiation (cauda epididymal sperm), PH-20 and PH-30 proteins were restricted to the posterior head domain and AH-50 was restricted to the anterior head domain. Thus these proteins become restricted in their distribution late in sperm differentiation, after sperm leave the testis. We discovered that the differentiation process that localizes these proteins can be mimicked in vitro by treating testicular sperm with trypsin. After testicular sperm were treated with 20 micrograms/ml trypsin for 5 min at room temperature, PH-20, PH-30, and AH-50 were found localized to the same domains to which they are restricted during in vivo differentiation. The in vitro trypsin-induced localization of PH-20 to the posterior head mimicked the in vivo differentiation process quantitatively as well as qualitatively. The quantitative analysis showed the process of PH-20 localization involves the migration of surface PH-20 from other regions to the posterior head domain. Immunoprecipitation experiments confirmed that there is protease action in vivo on the sperm surface during the late stages of sperm differentiation. Both the PH 20 and PH-30 proteins were shown to be proteolytically cleaved late in sperm differentiation. These findings strongly implicate proteolysis of surface molecules as an initial step in the mechanism of formation of sperm head surface domains. PMID- 2229176 TI - A beta-spectrin isoform from Drosophila (beta H) is similar in size to vertebrate dystrophin. AB - Spectrins are a major component of the membrane skeleton in many cell types where they are thought to contribute to cell form and membrane organization. Diversity among spectrin isoforms, especially their beta subunits, is associated with diversity in cell shape and membrane architecture. Here we describe a spectrin isoform from Drosophila that consists of a conventional alpha spectrin subunit complexed with a novel high molecular weight beta subunit (430 kD) that we term beta H. The native alpha beta H molecule binds actin filaments with high affinity and has a typical spectrin morphology except that it is longer than most other spectrin isoforms and includes two knoblike structures that are attributed to a unique domain of the beta H subunit. Beta H is encoded by a different gene than the previously described Drosophila beta-spectrin subunit but shows sequence similarity to beta-spectrin as well as vertebrate dystrophin, a component of the membrane skeleton in muscle. By size and sequence similarity, dystrophin is more similar to this newly described beta-spectrin isoform (beta H) than to other members of the spectrin gene family such as alpha-spectrin and alpha-actinin. PMID- 2229178 TI - Myosin mRNA accumulation and myofibrillogenesis at the myotendinous junction of stretched muscle fibers. AB - Myofiber growth and myofibril assembly at the myotendinous junction (MTJ) of stretch-hypertrophied rabbit skeletal muscle was studied by in situ hybridization, immunofluorescence, and electron microscopy. In situ hybridization identified higher levels of myosin heavy chain (MHC) mRNA at the MTJ of fibers stretched for 4 d. Electron microscopy at the MTJ of these lengthening fibers revealed a large cytoplasmic space devoid of myofibrils, but containing polysomes, sarcoplasmic reticulum and T-membranes, mitochondria, Golgi complexes, and nascent filament assemblies. Tallies from electron micrographs indicate that myofibril assembly in stretched fibers followed a set sequence of events. (a) In stretched fiber ends almost the entire sarcolemmal membrane was electron dense but only a portion had attached myofibrils. Vinculin, detected by immunofluorescence, was greatly increased at the MTJ membrane of stretched muscles. (b) Thin filaments were anchored to the sarcolemma at the electron dense sites. (c) Thick filaments associated with these thin filaments in an unregistered manner. (d) Z-bodies splice into thin filaments and subsequently thin and thick filaments fall into sarcomeric register. Thus, the MTJ is a site of mRNA accumulation which sets up regional protein synthesis and myofibril assembly. Stretched muscles also lengthen by the addition of myotubes at their ends. After 6 d of stretch these myotubes make up the majority of fibers at the muscle ends. Essentially all these myotubes repeat the developmental program of primary myotubes and express slow MHC. MHC mRNA distribution in myotubes is disorganized as is the distribution of their myofibrils. PMID- 2229177 TI - Primary structure of the 175K Plasmodium falciparum erythrocyte binding antigen and identification of a peptide which elicits antibodies that inhibit malaria merozoite invasion. AB - The Plasmodium falciparum gene encoding erythrocyte binding antigen-175 (EBA 175), a putative receptor for red cell invasion (Camus, D., and T. J. Hadley. 1985. Science (Wash. DC). 230:553-556.), has been isolated and characterized. DNA sequencing demonstrated a single open reading frame encoding a translation product of 1,435 amino acid residues. Peptides corresponding to regions on the deduced amino acid sequence predicted to be B cell epitopes were assessed for immunogenicity. Immunization of mice and rabbits with EBA-peptide 4, a synthetic peptide encompassing amino acid residues 1,062-1,103, produced antibodies that recognized P. falciparum merozoites in an indirect fluorescent antibody assay. When compared to sera from rabbits immunized with the same adjuvant and carrier protein, sera from rabbits immunized with EBA-peptide 4 inhibited merozoite invasion of erythrocytes in vitro by 80% at a 1:5 dilution. Furthermore, these sera inhibited the binding of purified, authentic EBA-175 to erythrocytes, suggesting that their activity in inhibiting merozoite invasion of erythrocytes is mediated by blocking the binding of EBA-175 to erythrocytes. Since the nucleotide sequence of EBA-peptide 4 is conserved among seven strains of P. falciparum from throughout the world (Sim, B. K. L. 1990. Mol. Biochem. Parasitol. 41:293-296.), these data identify a region of the protein that should be a focus of vaccine development efforts. PMID- 2229179 TI - Localization of myosin IC and myosin II in Acanthamoeba castellanii by indirect immunofluorescence and immunogold electron microscopy. AB - Polyclonal antisera have been raised against purified Acanthamoeba myosin II and to a synthetic 26 amino acid peptide that corresponds in sequence to the phosphorylation site of Acanthamoeba myosin IC. These antisera are specific for their respective antigens as determined by immunoblotting after SDS-PAGE of total cell lysates. By using the antisera, localization studies were performed by indirect immunofluorescence and by immunogold electron microscopy. Myosin II occurred in the cell cytoplasm and appeared to be concentrated in the cortex. Immunogold cytochemistry revealed at high resolution that myosin II is organized into rodlike filaments approximately 200 nm long. The antibody raised against the myosin IC synthetic peptide recognized both the plasma membrane and the membrane of the contractile vacuole. The plasma membrane staining was labile to treatment with saponin suggesting an intimate association of the myosin IC with membrane phospholipids. Immunogold cytochemistry with the antimyosin IC synthetic peptide showed that the myosin IC is closely associated with the membrane bilayer. PMID- 2229180 TI - Mechanism of the formation of contractile ring in dividing cultured animal cells. II. Cortical movement of microinjected actin filaments. AB - The contractile ring in dividing animal cells is formed primarily through the reorganization of existing actin filaments (Cao, L.-G., and Y.-L. Wang. 1990. J. Cell Biol. 110:1089-1096), but it is not clear whether the process involves a random recruitment of diffusible actin filaments from the cytoplasm, or a directional movement of cortically associated filaments toward the equator. We have studied this question by observing the distribution of actin filaments that have been labeled with fluorescent phalloidin and microinjected into dividing normal rat kidney (NRK) cells. The labeled filaments are present primarily in the cytoplasm during prometaphase and early metaphase, but become associated extensively with the cell cortex 10-15 min before the onset of anaphase. This process is manifested both as an increase in cortical fluorescence intensity and as movements of discrete aggregates of actin filaments toward the cortex. The concentration of actin fluorescence in the equatorial region, accompanied by a decrease of fluorescence in polar regions, is detected 2-3 min after the onset of anaphase. By directly tracing the distribution of aggregates of labeled actin filaments, we are able to detect, during anaphase and telophase, movements of cortical actin filaments toward the equator at an average rate of 1.0 micron/min. Our results, combined with previous observations, suggest that the organization of actin filaments during cytokinesis probably involves an association of cytoplasmic filaments with the cortex, a movement of cortical filaments toward the cleavage furrow, and a dissociation of filaments from the equatorial cortex. PMID- 2229181 TI - Components of the yeast spindle and spindle pole body. AB - Yeast spindle pole bodies (SPBs) with attached nuclear microtubles were enriched approximately 600-fold from yeast cell extracts. 14 mAbs prepared against this enriched SPB fraction define at least three components of the SPB and spindle. Immunofluorescent staining of yeast cells showed that throughout the cell cycle two of the components (110 and 90 kD) were localized exclusively to the SPB region, and the other (80 kD) was localized both to the SPB region and to particulate dots in short spindles. Immunoelectron microscopy confirmed and extended most of these findings. Thus the 110-kD component was localized to a layer in the SPB just to the nuclear side of the plane of the inner nuclear membrane. The 90-kD component was localized in a layer across the cytoplasmic face of intact SPBs, and, in SPBs where nuclear microtubules were removed by extraction with DEAE-dextran, the 90-kD component was also found in an inner nuclear layer close to where spindle microtubules emerge. In intact SPBs with attached nuclear microtubules the anit-80-kD mAb labels microtubules, particularly those close to the SPB. These results begin to provide a preliminary molecular map of the SPB and should also enable the corresponding genes to be isolated. PMID- 2229182 TI - Spatial and temporal colocalization of the Golgi apparatus and microtubules rich in detyrosinated tubulin. AB - The integrity and intracellular distribution of the Golgi apparatus appear to depend upon microtubules. We have found that the microtubules rich in detyrosinated tubulin are located preferentially in the vicinity of the Golgi. Cells were double-stained with antibodies specific for either tyrosinated or detyrosinated tubulin and an antibody to prolactin or wheat germ agglutinin (Golgi markers). Microtubules rich in detyrosinated tubulin showed a close codistribution with the Golgi in three different cultured cell lines GH3, BS-C-1, and AtT20. Disruption of microtubules with nocodazole in GH3 cells resulted in fragmentation and dispersal of the Golgi apparatus as reported previously. During recovery of the microtubules and the Golgi complex after removal of the nocodazole, there was a spatial and temporal colocalization of the Golgi apparatus and microtubules rich in detyrosinated tubulin. Our results suggest that a functional relationship may exist between the structure and organization of the Golgi complex and the detyrosination of alpha-tubulin in microtubules. PMID- 2229183 TI - Growth cone behavior and production of traction force. AB - The growth cone must push its substrate rearward via some traction force in order to propel itself forward. To determine which growth cone behaviors produce traction force, we observed chick sensory growth cones under conditions in which force production was accommodated by movement of obstacles in the environment, namely, neurites of other sensory neurons or glass fibers. The movements of these obstacles occurred via three, different, stereotyped growth cone behaviors: (a) filopodial contractions, (b) smooth rearward movement on the dorsal surface of the growth cone, and (c) interactions with ruffling lamellipodia. More than 70% of the obstacle movements were caused by filopodial contractions in which the obstacle attached at the extreme distal end of a filopodium and moved only as the filopodium changed its extension. Filopodial contractions were characterized by frequent changes of obstacle velocity and direction. Contraction of a single filopodium is estimated to exert 50-90 microdyn of force, which can account for the pull exerted by chick sensory growth cones. Importantly, all five cases of growth cones growing over the top of obstacle neurites (i.e., geometry that mimics the usual growth cone/substrate interaction), were of the filopodial contraction type. Some 25% of obstacle movements occurred by a smooth backward movement along the top surface of growth cones. Both the appearance and rate of movements were similar to that reported for retrograde flow of cortical actin near the dorsal growth cone surface. Although these retrograde flow movements also exerted enough force to account for growth cone pulling, we did not observe such movements on ventral growth cone surfaces. Occasionally obstacles were moved by interaction with ruffling lamellipodia. However, we obtained no evidence for attachment of the obstacles to ruffling lamellipodia or for directed obstacle movements by this mechanism. These data suggest that chick sensory growth cones move forward by contractile activity of filopodia, i.e., isometric contraction on a rigid substrate. Our data argue against retrograde flow of actin producing traction force. PMID- 2229184 TI - Antisense inhibition of glial S100 beta production results in alterations in cell morphology, cytoskeletal organization, and cell proliferation. AB - The phenotypic effects of selectively decreasing the levels of S100 beta in cultured glial cells were analyzed. Two separate antisense approaches were utilized for inhibition of S100 beta production: analysis of clonal isolates of rat C6 glioma cells containing an S100 beta antisense gene under the control of a dexamethasone-inducible promoter, and analysis of C6 cells treated with S100 beta antisense oligodeoxynucleotides. Both antisense methods resulted in a decrease in S100 beta levels in the cell, as measured by RIA. The inhibition of S100 beta production correlated with three alterations in cellular phenotype: (a) a flattened cell morphology; (b) a more organized microfilament network; and (c) a decrease in cell growth rate. The studies describe here provide direct evidence for an involvement of S100 beta in glial cell structure and function, and suggest potential in vivo roles for S100 beta in regulation of glial cell morphology, cytoskeletal organization, and cell proliferation. PMID- 2229185 TI - Acetylcholine receptor clustering is triggered by a change in the density of a nonreceptor molecule. AB - Acetylcholine receptors become clustered at the neuromuscular junction during synaptogenesis, at least in part via lateral migration of diffusely expressed receptors. We have shown previously that electric fields initiate a specific receptor clustering event which is dependent on lateral migration in aneural muscle cell cultures (Stollberg, J., and S. E. Fraser. 1988. J. Cell Biol. 107:1397-1408). Subsequent work with this model system ruled out the possibility that the clustering event was triggered by increasing the receptor density beyond a critical threshold (Stollberg, J., and S. E. Fraser. 1990. J. Neurosci. 10:247 255). This leaves two possibilities: the clustering event could be triggered by the field-induced change in the density of some other molecule, or by a membrane voltage-sensitive mechanism (e.g., a voltage-gated calcium signal). Electromigration is a slow, linear process, while voltage-sensitive mechanisms respond in a rapid, nonlinear fashion. Because of this the two possibilities make different predictions about receptor clustering behavior in response to pulsed or alternating electric fields. In the present work we have studied subcellular calcium distributions, as well as receptor clustering, in response to such fields. Subcellular calcium distributions were quantified and found to be consistent with the predicted nonlinear response. Receptor clustering, however, behaves in accordance with the predictions of a linear response, consistent with the electromigration hypothesis. The experiments demonstrate that a local increase in calcium, or, more generally, a voltage-sensitive mechanism, is not sufficient and probably not necessary to trigger receptor clustering. Experiments with slowly alternating electric fields confirm the view that the clustering of acetylcholine receptors is initiated by a local change in the density of some non receptor molecule. PMID- 2229186 TI - Properties of the desmin tail domain: studies using synthetic peptides and antipeptide antibodies. AB - Intermediate filament (IF) proteins have a common structural motif consisting of an alpha-helical rod domain flanked by non-alpha-helical amino-terminal head and carboxy-terminal tail domains. Coiled-coil interaction between neighboring rod domains is though to generate the backbone of the 10-nm filament. There must also be other interactions between subunits to bring them into alignment and to effect elongation of the filament, but these are poorly understood. To examine the involvement of the tail domain in filament structure and stabilization, we have studied the interaction between a synthetic peptide corresponding to residues 442 450 of avian desmin, and authentic desmin protein. The potential importance of this region lies in its hydrophilic nature and its high degree of homology among the Type III IF proteins and cytokeratins 8 and 18. The peptide, D442-450, binds to a 27-residue region between lys-436 and leu-463, the carboxy terminus. The presence of the peptide during assembly causes the filaments to appear much more loosely packed than normal desmin IF. We have also generated polyclonal antibodies against this peptide and attempted to localize this portion of the tailpiece along desmin IFs by immunological procedures. By immunoblotting, we found that anti-D442-450 antibodies recognize desmin and only those proteolytic fragments that contain the tailpiece. In contrast, the antibodies do not label any structure in adult gizzard smooth muscle and skeletal muscle myofibrils in immunofluorescence experiments during which conventional antidesmin antibodies do. At the ultrastructural level, anti-D442-450 antibodies label free desmin tetramers but not desmin IFs. These results show that, as part of an assembled IF, the epitope of anti-D442-450 is inaccessible to the antibodies, and suggest that either the tailpiece of an IF protein may not be entirely peripheral to the filament backbone, or the interaction between end domains during assembly masks this particular region of the IF molecule. PMID- 2229187 TI - Epithelial origin of cutaneous anchoring fibrils. AB - Anchoring fibrils are essential structural elements of the dermoepidermal junction and are crucial to its functional integrity. They are composed largely of type VII collagen, but their cellular origin has not yet been confirmed. In this study, we demonstrate that the anchoring fibrils are primarily a product of epidermal keratinocytes. Human keratinocyte sheets were transplanted to a nondermal connective tissue graft bed in athymic mice. De novo anchoring fibril formation was studied ultrastructurally by immunogold techniques using an antiserum specific for human type VII procollagen. At 2 d after grafting, type VII procollagen/collagen was localized both intracellularly within basal keratinocytes and extracellularly beneath the discontinuous basal lamina. Within 6 d, a subconfluent basal lamina had developed, and newly formed anchoring fibrils and anchoring plaques subjacent to the xenografts were labeled. Throughout the observation period of the experiment, the maturity, population density, and architectural complexity of anchoring fibrils beneath the human epidermal graft continuously increased. Identical findings were obtained using xenografts cultivated from cloned human keratinocytes, eliminating the possibility of contributions to anchoring fibril regeneration from residual human fibroblasts. Immunolabeling was not observed at the mouse dermoepidermal junction at any time. These results demonstrate that the type VII collagen of human cutaneous anchoring fibrils and plaques is secreted by keratinocytes and can traverse the epidermal basal lamina and that the fibril formation can occur in the absence of cells of human dermal origin. PMID- 2229188 TI - Identification of a novel glycoprotein (AGp110) involved in interactions of rat liver parenchymal cells with fibronectin. AB - We have identified an integral membrane glycoprotein in rat liver that mediates adhesion of cultured hepatocytes on fibronectin substrata. The protein was isolated by affinity chromatography of detergent extracts on wheat germ lectin Agarose followed by chromatography of the WGA binding fraction on fibronectin Sepharose. The glycoprotein (AGp110), eluted at high salt concentrations from the fibronectin column, has a molecular mass of 110 kD and a pI of 4.2. Binding of immobilized AGp110 to soluble rat plasma fibronectin required Ca2+ ions but was not inhibited by RGD peptides. Fab' fragments of immunoglobulins raised in rabbits against AGp110 reversed the spreading of primary hepatocytes attached onto fibronectin-coated substrata, but had no effect on cells spread on type IV collagen or laminin substrata. The effect of the antiserum on cell spreading was reversible. AGp110 was detected by immunofluorescence around the periphery of the ventral surface of substratum attached hepatocytes, and scattered on the dorsal surface. Immunohistochemical evidence and Western blotting of fractionated liver plasma membranes indicated a bile canalicular (apical) localization of AGp110 in the liver parenchyma. Expression of AGp110 is tissue specific: it was found mainly in liver, kidney, pancreas, and small intestine but was not detected in stomach, skeletal muscle, heart, and large intestine. AGp110 could be labeled by lactoperoxidase-catalyzed surface iodination of intact liver cells and, after phase partitioning of liver plasma membranes with the detergent Triton X-114, it was preferentially distributed in the hydrophobic phase. Treatment with glycosidases indicated extensive sialic acid substitution in at least 10 O-linked carbohydrate chains and 1-2 N-linked glycans. Immunological comparisons suggest that AGp110, the integrin fibronectin receptor and dipeptidyl peptidase IV, an enzyme involved in fibronectin-mediated adhesion of hepatocytes on collagen, are distinct proteins. PMID- 2229190 TI - Mapping MAP-2. PMID- 2229189 TI - Human smooth muscle VLA-1 integrin: purification, substrate specificity, localization in aorta, and expression during development. AB - A membrane glycoprotein complex was isolated and purified from human smooth muscle by detergent solubilization and affinity chromatography on collagen Sepharose. The complex was identified as VLA-1 integrin and consisted of two subunits of 195 and 130 kD in SDS-PAGE. Liposomes containing the VLA-1 integrin adhered to surfaces coated with type I, II, III, and IV collagens, Clq subcomponent of the first component of the complement, and laminin. The liposomes specifically adhered to these proteins in a Ca2+, Mg2(+)-dependent manner, but did not bind to gelatin, fibronectin, and thrombospondin substrates. The expression of VLA-1 integrin in different human tissues and cell types, and during aorta smooth muscle development was studied by SDS-PAGE, and subsequent quantitative immunoblotting was performed with antibodies recognizing alpha 1 and beta 1 subunits of the VLA-1 integrin. A high level of VLA-1 integrin expression was an exceptional feature of smooth muscles. Fibroblasts, endothelial cells, keratinocytes, striated muscles, and platelets contained trace amounts of VLA-1 integrin. In the 10-wk-old human fetal aorta, VLA-1 integrin was found only in smooth muscle cells whereas mesenchymal cells, surrounding aortic smooth muscle cells, were VLA-1 integrin negative. By the 24th wk of gestation, the amount of VLA-1 integrin was significantly reduced in the aortic media (4.3-fold for alpha 1 subunit and 2.5-fold for beta 1 subunit) compared with that in the 10-wk-old aortic smooth muscle cells. After birth, the expression of VLA-1 integrin increased and in the 1.5-yr-old child aorta the VLA-1 integrin level was almost the same as in adult aortic media. Smooth muscle cells from intimal thickening of adult aorta express five times less alpha 1 subunit of VLA integrin that smooth muscle cells from adult aortic media. In primary culture of aortic smooth muscle cells, the content of the VLA-1 integrin was dramatically reduced and subcultured cells did not contain VLA-1 integrin at all. PMID- 2229191 TI - Localization of human growth hormone to a sub-set of cytoplasmic vesicles in transfected PC12 cells. AB - Two distinct population of vesicles can be identified in PC12 cells by subcellular fractionation and immunofluorescence. Density gradient separation reveals one population of dense vesicles that contains the transgenic regulated secretory protein hGH (human growth hormone) along with the endogenous neurotransmitter norepinephrine. Some of the neuronal vesicle marker synaptophysin (P38) is also associated with these vesicles. A second population of low-density vesicles contains synaptophysin but not hGH or norepinephrine. Immunofluorescence localization of hGH revealed a pattern consistent with packaging into catecholaminergic vesicles: the staining is punctate and most concentrated in the tips of the neuritic processes, with secondary accumulation in the perinuclear region. Double-staining of cells for hGH and synaptophysin confirms that these proteins do not co-localize but rather are spatially segregated within the cell. The observed distribution of vesicle markers is inconsistent with simple models for the generation of one type of vesicle from the other, suggesting that the vesicles are products of two divergent biosynthetic pathways. While the hGH is clearly contained in regulated secretory vesicles, the function of the second population of vesicles remains uncertain. PMID- 2229192 TI - Variable pathways for developmental changes in composition and organization of microtubules in Physarum polycephalum. AB - The development of uninucleate amoebae into multinucleate plasmodia in myxomycetes is called the amoebal-plasmodial transition (APT). During the APT in Physarum polycephalum the ability to form flagellar axonemes is lost; the astral, open mitosis is replaced by the anastral, closed mitosis; and cytoskeletal microtubules disappear. These changes are accompanied by alterations in the repertoire of expressed tubulins. Using immunofluorescence microscopy we have studied the timing of loss and accumulation of developmentally regulated tubulin isotypes in relation to other cellular events during the APT. We specifically asked whether changes in the composition of microtubules are correlated with changes in their organization. The plasmodium-specific beta 2-tubulin can first be detected in microtubules of uninucleate cells after they become committed to plasmodium formation. However, rare cells are observed that exhibit beta 2 tubulin at earlier or only at later stages of development. Amoeba-specific acetylated alpha 3-tubulin disappears gradually during development. Individual cells differ in the timing of loss of this isotype: alpha 3-tubulin is present in the majority of uninucleate cells, in a fraction of binucleate and quadrinucleate cells, and is absent from larger multinucleate cells. Cytoplasmic microtubules in uninucleate cells are organized by a single microtubule-organizing center (MTOC) juxtaposed to the nucleus. Binucleate cells and quadrinucleate cells exhibit variable numbers of MTOCs. Cytoplasmic microtubules persist during the APT until the stage of plasmodia containing at least 100 nuclei. The lack of a strict correlation between the changes in tubulin composition and changes in organization of microtubular structures indicates that accumulation of beta 2 tubulin and disappearance of alpha 3-tubulin isotypes are not sufficient to bring about reorganization of microtubules during development. Individual cells in a developing population differ not only in the succession of accumulation and loss of developmentally regulated tubulins, but also in the sequences of other cellular changes occurring during the APT. PMID- 2229193 TI - Phosphorylation of algal centrin is rapidly responsive to changes in the external milieu. AB - Centrin, a calcium-sensitive contractile phosphoprotein, is the major component of the striated flagellar roots of the flagellate green alga, Tetraselmis striata. Flagellar roots contract in response to elevated calcium levels. Data presented here indicate that the level of centrin phosphorylation is rapidly responsive to changes in the cell's external environment. Centrin is dephosphorylated in response to elevated calcium or to heat shock. An increase in centrin phosphorylation accompanies pH shock or ethanol treatment. These changes are compared with flagellar excision, flagellar root contraction, and protein synthesis under the same treatments. We conclude that under certain conditions phosphorylation/dephosphorylation of centrin and extension/contraction of the flagellar root are uncoupled. Possible role(s) of centrin phosphorylation independent of force generation in the flagellar root are discussed. PMID- 2229194 TI - The monovalent ionophore monensin maintains the nuclear localization of the human stress protein hsp28 during heat shock recovery. AB - In HeLa cells exposed to supra-optimal temperatures, the alpha-crystallin-related stress protein hsp28 is reversibly redistributed inside the nucleus and increases its level of phosphorylation and aggregation. Here, I show that, at normal temperature after a heat stress, the sodium ionophore monensin maintains the nuclear localization of hsp28 without impairing the dephosphorylation of this protein. This phenomenon is not due to a prolongation, by monensin, of the synthesis of the heat-shock proteins after the heat stress. In contrast, the potassium ionophore nonactin induces only a weak alteration in the hsp28 locale, while the calcium ionophore A23187 and the uncoupler of oxidative phosphorylation FCCP have no effect. Following the removal of monensin 15 h after the heat stress, a further incubation of the cells for at least 36 h is necessary in order to observe a redistribution of hsp28 into the cytoplasm. A large fraction of hsp28 is then observed as dense excretion granules. In control cells kept at normal temperature, monensin, like nonactin, A23187 and FCCP, does not induce the redistribution of hsp28 inside the nucleus. Taken together, these results suggest that the disruption of the Na+ active transport by monensin probably inhibits the redistribution of hsp28 in the cytoplasm after heat shock. PMID- 2229195 TI - Continued DNA synthesis after a mitotic block in the double mutant cut1 cdc11 of the fission yeast Schizosaccharomyces pombe. AB - DNA synthesis is normally dependent on a cell having previously gone through mitosis. Hirano et al. (1986), however, found that DNA synthesis continued at the restrictive temperature in the double mutant cut1 cdc11 of Schizosaccharomyces pombe even though mitosis was blocked in some of the cells. We have confirmed this result with bulk DNA assays of asynchronous cultures. Synchronous cultures of a diploid double mutant at the restrictive temperature showed two peaks of incorporation with an interval between them that was approximately the same as the doubling time in cell length. Flow cytometry showed that the cells had increased their DNA content from 4C (the diploid value) to about 16C after 7h. The cytological appearance at this time was mixed, with uninucleate, binucleate and dead cells, but fluorescence measurements on single cells indicated that about half the population had single nuclei with about the 16C value and had therefore gone through two rounds of DNA synthesis without mitosis. PMID- 2229196 TI - Cytoplasmic pool of histone H1 in mammalian cells. AB - Two types of cell populations, nondividing mouse liver cells and exponentially growing Friend erythroleukemia cells, were studied for the presence of a histone H1 pool in the cytoplasm. Purified cytoplasmic fractions were extracted with 5% perchloric acid and the resulting protein preparation was characterized by two types of electrophoresis, gel filtration, peptide mapping, ELISA and immunoblotting. The occurrence of significant quantities of H1 in isolated cytoplasmic fractions was confirmed by indirect immunofluorescence on whole cells. The existence of a cytoplasmic pool of H1 contrasts with the lack of detectable amounts of core histones in the cytoplasm. This indicates that the observed H1 pool is not just a reflection of its cytoplasmic synthesis but probably has some functional significance. PMID- 2229197 TI - Monoclonal antibody study of the decorated spongiome of contractile vacuole complexes of Paramecium. AB - A monoclonal antibody (mAb) has been developed and selected by immunofluorescence for the radial canals of the contractile vacuole complex (CVC) of Paramecium multimicronucleatum. By applying indirect immunogold labeling to thin frozen sections this mAb has been shown at the electron microscopic level to be specific for the decorated spongiome. We have used the mAb to study the normal interfission appearance as well as developmental stages of the decorated spongiomes. Two decorated spongiomes, presumably involved in water sequestration, radiate as 5-10 bands from unlabeled, circular, 25 microns diameter centers. Two new CVCs arise just anterior to the space occupied by the old spongiomes, the new anterior CVC appearing slightly before the posterior one. Development of the new spongiomes around a 10 microns unlabeled central zone is accompanied by a regression of old spongiome bands until the lengths of these bands in both old and new CVCs are equal just before cell division. After division both old and new spongiome bands grow at equal rates to the same length. Exceptions to the above general scheme, both in number of CVCs in interfission, as well as in position of the new relative to the old CVCs, are also observed. PMID- 2229198 TI - Fodrin in the human polymorphonuclear leucocyte: redistribution induced by the chemotactic peptide. AB - Fodrin, a membrane skeletal protein, was found to accumulate in the posterior portion of human neutrophils polarized morphologically after stimulation by the chemotactic peptide, N-formylmethionyl-leucylphenylalanine (FMLP). In most (greater than 90%) unstimulated neutrophils, the distribution of fodrin was found to be uniform by immunofluorescence microscopy. When FMLP (10(-8)M) was applied at 25 degrees C, fodrin became polarized in about 40% of cells by 1 min, about 70% by 2 min, and about 80% by 10 min. The cells with polarized distribution decreased thereafter to about 60% of the cells at 20 min and about 20% at 60 min. Using the under-agarose system, it was confirmed that the concentration of fodrin occurred in the region opposite to the direction of chemoattraction in moving cells. By immunoelectron microscopy, most of the labeling for fodrin was observed in the filamentous cell cortex and not associated with the plasma membrane itself. In cells polarized morphologically by FMLP, the fodrin labeling became concentrated in the posterior portion of the cell; the labeling was found most densely in the granule-rich cytoplasm, while the filamentous tail region was not labeled intensely. The lamellipodium in the head region was also labeled only sparsely. The results indicate that in human neutrophils fodrin exists as a cytoskeletal protein rather than as a membrane protein and that the protein accumulates in the endoplasm of the posterior portion in migrating cells. The rearrangement is likely to modulate the organization of the actin-rich cell cortex for cell locomotion. PMID- 2229199 TI - Cysteine proteinase in Trypanosoma cruzi: immunocytochemical localization and involvement in parasite-host cell interaction. AB - A monospecific polyclonal antibody obtained against a cysteine proteinase isolated from epimastigotes of Trypanosoma cruzi was used for the immunocytochemical localization of the protein by electron microscopy and to analyse the role played by cysteine proteinase in the process of T. cruzi-host cell interaction. Cytoplasmic structures that correspond to elements of the endosomal-lysosomal (reservosome) system found in epimastigote, amastigote and trypomastigote forms reacted intensely with colloidal gold-labelled antibodies using on-section indirect labelling. The surface of most of the tissue culture derived trypomastigotes was not labelled. However, the flagellar pocket of this form was labelled. All epimastigotes obtained from axenic cultures and amastigote like forms found in the supernatant of vertebrate cells heavily infected with T. cruzi had their surface intensely labelled, indicating also the surface localization of the protein. Incubation of the parasites in the presence of a sub agglutinating concentration of the anti-cysteine proteinase antibody led to a marked increase in their uptake by macrophages. In contrast, addition of the F(ab')2 portion of the same antibody significantly reduced the uptake of the parasites by the macrophages. The results obtained strongly suggest an important participation of cysteine proteinase in the process of T. cruzi-macrophage interaction. PMID- 2229200 TI - Lysosomal enzyme secretory mutants of Dictyostelium discoideum. AB - Dictyostelium discoideum secretes a number of lysosomal enzymes during axenic growth and upon suspension in a low ionic strength, non-nutrient buffer (standard secretion conditions). These secretory characteristics have allowed us to identify 74 lysosomal enzyme secretory mutants generated by N-methyl-N'-nitro-N nitrosoguanidine mutagenesis. The majority of these mutants fell into one of four classes, on the basis of their secretory characteristics in non-nutrient buffer. The four mutant classes indicate that a minimum of three distinct sets of genes are necessary for proper secretion of lysosomal enzymes from D. discoideum cells under standard secretion conditions: one set of genes that is involved in general lysosomal enzyme secretion, one that is involved in glycosidase type secretion, and a third that is involved in acid phosphatase type secretion. These three classes likely reflect heterogeneity in the intracellular destination of lysosomal enzymes, the secretory mechanism, or both. A fourth set of genes may be necessary for proper secretion during growth, but plays no role under standard secretion conditions. These are likely altered in the regulation of secretion or in lysosomal enzyme targeting. Of the 74 secretory mutants, 36 were also modification mutants resulting in decreased pI, thermolability, or in vivo instability of lysosomal enzyme activities. The high frequency of modification mutants indicates an integral relationship between lysosomal enzyme modification, and lysosomal enzyme targeting and secretion in D. discoideum. PMID- 2229201 TI - Regulation by calcium of proliferation and morphology of normal human tracheobronchial epithelial cell cultures. AB - Human tracheobronchial epithelial cells have been serially passaged in serum-free medium. This serum-free model was employed to investigate the effects of different concentrations of Ca2+ (0.1, 1.0 and 2.0 mM) on multiplication and morphology of the cells. The responses were analysed in terms of growth kinetics, histochemical and ultrastructural alterations. Culturing of the cells in high Ca2+ (1.0-2.0 mM) medium stimulated cell multiplication characterized by increased colony forming efficiency, greater number of cells per colony and cell population doublings per day. Additionally, the high Ca2+ concentrations induced proliferation in cultures grown to confluency in low Ca2+ (0.1 mM) medium. Cells propagated in low Ca2+ medium consisted of relatively heterogeneous cell populations, with most cells staining positive with periodic acid-Schiff (PAS) reagent. Ultrastructurally the cells exhibited secretory vesicles and microvilli on their surfaces, small desmosomes and intercellular interdigitation between cells and numerous large secretory vesicles in the cytoplasm. The cells grown in high Ca2+ medium acquired characteristics of a highly proliferative phenotype. The cultures consisted of closely packed, relatively homogeneous cells that did not stain with PAS reagent. Their characteristic features were: absence of surface secretory vesicles, reductions of microvilli and intercellular interdigitations, and increases in size and number of desmosomal junctions. The results show that low Ca2+ in the culture medium inhibits cell multiplication and favors the secretory cell phenotype, while high Ca2+ levels stimulate cell multiplication and inhibit the secretory cell phenotype. PMID- 2229202 TI - An analysis of chick limb bud intercellular adhesion underlying the establishment of cartilage aggregates in suspension culture. AB - To examine the mechanism of intercellular adhesion in the establishment of limb skeletal elements we have investigated the process of limb bud cell aggregation in vitro. Limb bud cells are aggregation-competent immediately after their trypsin:collagenase dissociation in the absence of calcium. This aggregation is largely Ca2(+)-independent (CI) and is completely and reversibly inhibited by cycloheximide. In contrast, when limb bud cells are first allowed to recover from Ca2(+)-free trypsin:collagenase dissociation, aggregation of the surviving population is exclusively Ca2(+)-dependent (CD) and completely and reversibly inhibited by cycloheximide. The presence of exogenous calcium during initial cell dissociation retains a functional CD aggregation mechanism. However, incubation of such cells with EGTA releases the CD component and converts the cells to a predominantly CI aggregation. Rabbits were immunized with limb bud cells exhibiting the recovered CD aggregation mechanism and the resulting immune sera were screened for their effect on cell aggregation. Relative to pre-immune sera, intact immune IgG agglutinated dissociated limb bud cells whilst immune Fab fragments inhibited their aggregation. The aggregation-inhibiting antiserum recognizes five major limb bud cell surface components with apparent molecular weights of 72K, 50K, 23K, 14.5K and 8.5K (K = 10(3) Mr), respectively. Limb bud cell surface plasma membranes were isolated by sucrose gradient density centrifugation and detergent-solubilized proteins coupled to Sepharose 4B with cyanogen bromide. Equivalent cell surface plasma membrane proteins were 125I iodinated and applied to the affinity column. Limb bud cell surface protein affinity chromatography in the presence of exogenous calcium yields a single protein with an apparent molecular weight of approximately 8.5 K. This protein molecule elutes at 0.6 M NaCl, indicating a high affinity, is recognized by the aggregation-inhibiting antiserum, and is itself capable of inhibiting CD limb bud cell aggregation. Fab fragments prepared from rabbit antisera specifically directed against the affinity-purified material also inhibit CD limb bud cell aggregation and this inhibition is neutralized by the 8.5 K protein. Our data thus demonstrate that CD limb bud cell aggregation is not mediated by fibronectin and/or collagen type I and indicate that this process is governed by a novel 8.5 K cell adhesion molecule. PMID- 2229203 TI - The therapeutic role of gangliosides. PMID- 2229204 TI - Factors influencing pharmacists' participation in third-party programmes. PMID- 2229205 TI - High-performance liquid chromatographic analysis of indomethacin in serum. AB - A rapid high-performance liquid chromatographic (HPLC) method for quantitative determination of indomethacin in serum is described. The assay was performed after single extraction of indomethacin and itraconazole (internal standard) from serum using diethyl ether and eluted from a 4 micron C-18 reversed-phase column at ambient temperature. The mobile phase consisted of ethanol:water:glacial acetic acid (65:34:1, v/v) pumped isocratically at a flow rate of 1.3 ml/min. The effluent was monitored at 254 nm. Quantification was achieved by the measurement of the peak area ratio, and the absolute recoveries ranged from 94 to 97%. Within day coefficients of variation (CV) ranged from 2.72 to 5.70% and between-day CV varied from 3.61 to 6.1%. Stability testing indicated that indomethacin is stable for at least 30 days in serum at -20 degrees C. The method was used to study indomethacin pharmacokinetics in rabbits. PMID- 2229206 TI - Patterns of out-patients non-steroidal anti-inflammatory drug prescribing in two teaching hospital rheumatology units--implications for post-marketing surveillance. AB - Patterns of prescriptions or recommendations for non-steroidal anti-inflammatory drugs (NSAIDs) were examined in the out-patient departments of two teaching hospital rheumatology units [The General Infirmary, Leeds (n = 140), and Musgrave Park Hospital, Belfast (n = 77)]. In both units four drugs accounted for over 80% of prescriptions/recommendations (diclofenac, indomethacin, ibuprofen and naproxen in Leeds and flurbiprofen, nabumetone, ibuprofen and diclofenac in Belfast). In Leeds patients with pre-existing upper gastrointestinal problems were more likely to receive diclofenac whereas in Belfast they were more likely to receive nabumetone or ibuprofen. In Leeds, patients who received indomethacin tended to be young males with seronegative arthritis. These differences between drugs and between centres could have important implications for cost, design and interpretation of studies of post-marketing surveillance. PMID- 2229207 TI - Stability of doxorubicin, daunorubicin and epirubicin in plastic syringes and minibags. AB - The shelf lives of doxorubicin, daunorubicin and epirubicin in infusion fluids were studied using high-performance liquid chromatographic (HPLC) methods. Doxorubicin and epirubicin were stable (loss in potency of less than 10%) for 24 and 20 days respectively, when dissolved in sodium chloride solution (0.9%; pH, 6.47) at 25 degrees C and stored in polyvinyl chloride (PVC) minibags, while daunorubicin was stable for at least 43 days. All three drugs were stable for at least 43 days in sodium chloride (0.9%; pH 6.47 and 5.20) and dextrose (5%; pH 4.36) at 4 and -20 degrees C. Repeated thawing and re-freezing of these solutions at ambient temperature did not cause degradation. All three drugs were stable for at least 43 days when reconstituted with Water-for-Injections BP and stored in polypropylene syringes at 4 degrees C. PMID- 2229208 TI - Photodegradation of doxorubicin, daunorubicin and epirubicin measured by high performance liquid chromatography. AB - The degradation kinetics of doxorubicin, daunorubicin and epirubicin in aqueous solution under fluorescent light and sunlight were studied using high-performance liquid chromatographic (HPLC) methods. The rates of photodegradation of all three drugs were similar, they were inversely proportional to the drug concentration and were accelerated by an increase in the pH of the vehicle. Photodegradation followed first-order kinetics. At concentrations greater than or equal to 500 micrograms/ml no special precautions appeared to be necessary to protect freshly prepared solutions of these agents from light. Photolysis was very rapid, however, at concentrations in the low microgram range therefore, when these solutions are used for in-vitro work or stability studies, they should be protected from light at all times. In addition, adsorptive losses, which may also be pronounced in low concentration solutions, should be prevented by storage in polypropylene containers. PMID- 2229209 TI - Gastrointestinal symptoms. I. PMID- 2229210 TI - [Hydatid cysts of the liver appearing late (10 to 22 years) after surgical treatment of pulmonary hydatidosis. Physiopathologic problems]. AB - The very late observation of an hydatid cyst of the liver, after clinical or fortuitous signs (intraoperative, ultrasound, CT) is a highly underestimated possibility. From 4 cases of hydatid cysts of the liver which were removed 10 to 22 year after a pulmonary hydatidosis, any possibility of parasitic reinfestation during this time being excluded, the authors propose a physiopathological explanation to an often very long clinical latency period of the liver hydatidosis. Indeed the pulmonary location of the hydatid disease means that the hepatic filter did not properly operate or was bypassed, but it does not exclude a simultaneous intrahepatic graft. The literature study shows a 4 to 8.4% rate of concomitant liver-lung location according to the statistical data provided by thoracic and digestive surgery departments. The percentage reaches 25% when ultrasounds and abdominal computed tomography are systematically used. The rapid growth of the hydatid cyst in the lung can be explained by the low resistance of the lung parenchyma and vasculo-bronchial structure to the intracystic pressure, whereas in the liver, the hydatid cyst growing is stopped by a dense parenchyma and the hepatobiliary capsules. When fissuring or large opening in the biliary tract occurs the intracystic pressure drops, the pericyst becomes sclerotic, calcified. The combination of these different factors all the more contributes to the cyst involution since it presents a central topography. PMID- 2229211 TI - [A.L.J. external fixation. Indications and results in 59 cases]. AB - The authors report their results in 59 cases of external fixation with A.L.J. type devices inserted from November, 1984, to November, 1988, in 57 patients (2 cases of bilateral injuries). These included 49 cases of "recent" traumatology, 4 cases of "second-hand" traumatology, and 6 orthopaedic cases (tibiotarsal arthrodesis for degenerative lesions). Among the recent traumatic injuries, 38 were fractures, most often compound fractures (stages II and III), and 11 serious soft tissue lesions, for which the external fixation was used temporarily for stabilization until the wound was healed. The older traumatological lesions were 4 infected pseudarthroses. The results based on 52 cases (6 were lost to follow up and 1 is a peculiar case) include 45 healed injuries (ie. 86.5%) and 7 failures. The soft-tissue lesions have all healed within 2 to 4 months. Among the bony lesions, some knit primarily without an additional graft (20 of 37 cases, ie 54 percent), the others after 1, 2 or 3 grafts (10 of 37 cases, ie. 27 percent). The union also occurred without any problem for all 6 tibiotarsal arthrodeses. The 7 failures occurred in cases where no additional bone graft had been performed. The discussion evidences the advantages and drawbacks of the A.L.J. PMID- 2229212 TI - [Predictive factors of mortality and morbidity in colectomy patients over 75 years of age. Report of 69 cases]. AB - Sixty nine patients over 75 years old who had a colectomy were retrospectively studied. The carcinoma of the colon represented the main indication for 42 cases (60.9%) and 22 patients (31.9%) were immediately operated. The influence of parameters such as age, sex, visceral defects, emergency, performance of a colostomy or associated intervention, type of colic pathology, was statistically studied. The age (p less than 0.05), emergency (p less than 0.03) and the number of defects greater than or equal to 3 (p less than 0.04) contribute to mortality. The number of defects greater than or equal to 3 (p less than 0.006) contributes to general morbidity. Only complications connected with the operation by itself significantly prolong the duration of hospitalization (p less than 0.02). The authors draw the conclusion that the age by itself is not a contra-indication for operation except in case of associated polyvisceral failure. In addition, it is required to carry out an early detection of colic lesions in elderly subjects in order to contemplate surgery before complications whose prognosis is fearsome (54.5% of death in emergency operation). PMID- 2229213 TI - [Alcoholic pancreatitis and pseudocysts. Prospective study of 20 cases in Reunion Island]. AB - In the french indian ocean's island whose name is Reunion, between 1984 and 1986, 20 pancreatic pseudocysts, exclusively encountered in alcoholic patients, were submitted to a prospective study. Most of the lesion were very symptomatic, large and extrapancreatic. Accordingly to Marseille's classification, most of the patients were suffering from acute or chronic relapsing pancreatitis. 18 patients were submitted to a therapeutic procedure. Internal drainage was performed in 9 patients, and external drainage was performed in 5. In addition, pancreatic resection was carried out in 2 patients, and needle aspiration in 2. Comments concern potential specificities of the population which was studied. Special emphasis concern the necessity of preoperative computerized tomographic scanning, the indications of percutaneous external drainage and the long-term survival of patients. PMID- 2229214 TI - [Indications for arteriography in penetrating wounds of the lower limbs]. AB - One hundred arteriographies were performed in emergency in 87 patients with penetrating trauma of the lower limbs caused by high- or medium-velocity projectiles (bullet or shell fragment). Thirteen patients had bilateral wounds. In 79 cases, the arteriogram was abnormal and led to surgical exploration. In 76 cases, an arterial lesion was found and treated (positive predictive value = 76/79 = 96%). In three cases, no arterial lesion was detected (3 false-positive findings). Among the 21 patients with normal arteriograms, 10 had surgical exploration because of clinical suspicion. An arterial lesion was found in 2 cases (2 false-negative findings). In the other 11 cases, the clinical and Doppler sonographic observations were normal (negative predictive value = 19/21 = 90%). The sensitivity rate was 97%, specificity 86% and accuracy 95%. In 8 cases, arteriography led to modifying the surgical procedure. These results show that preoperative arteriography, performed as an emergent examination in hemodynamically stable patients, allows avoiding surgery in some cases, and modifying the procedure in others. PMID- 2229215 TI - [Gallbladder volvulus]. AB - We report two new cases of gallbladder volvulus. This rare condition principally affects elderly patients but is due to a congenital malformation related to the presence of a long mesocyst. Various factors such as kyphoscoliosis, multiparity and peristalsis of neighbouring organs favorise the occurrence of volvulus, the role of lithiasis is debatable. The diagnosis may be suggested on ultrasound but is most often confirmed at laparotomy. Diagnosis should be made rapidly in order to avoid progression towards a potentially fatal secondary peritonitis. Certain clinical elements such as the presence of a "floating mass" on palpation may suggest the diagnosis. PMID- 2229216 TI - [Adenocarcinoma at an ileostomy site after colectomy for ulcerative colitis]. AB - In this article we present the tenth case, according to the literature, of adenocarcinoma occurring at a long standing ileostomy originally performed for ulcerative colitis. Study of this and previous cases demonstrates common factors such as a previous history of ulcerative colitis, a long interval until the appearance of symptoms, together with a similar clinical and pathological characterisation with invasion of neighbouring skin layers close to the ileostomy. Several pathogenic hypotheses are considered. We believe that local excision in oder to obtain the diagnosis is a better option than a sampling biopsy and that surgery should include a wide resection of the abdominal wall and intestine in order to comply with therapeutic criteria in malignant disease. PMID- 2229217 TI - [Encapsulating peritonitis. Report of 2 cases]. AB - Walled-off peritonitis which is a frequent occurrence in patients treated by continuous ambulatory peritoneal dialysis may also occur in cases where there is no obvious pathological factor. This was the case in the two patients reported. Both were male patients aged 28 and 32 years hospitalised and operated on for acute intestinal obstruction. Positive diagnosis was made at the time of operation. Decortication with total enterolysis was performed in the two cases. However, a jejunal fistula with a favorable outcome occurred in one case, investigation for acid fast bacilli was negative and histological examination was non specific. PMID- 2229218 TI - [Digestive malacoplakia; observations on a colonic site]. PMID- 2229219 TI - [Malignant cutaneous melanoma with metastases in the small intestine]. PMID- 2229220 TI - [A rare cause of intestinal occlusion in the elderly]. PMID- 2229221 TI - [Cystic pneumatosis of the small intestine. A case report]. PMID- 2229222 TI - High-performance liquid chromatography of amino acids, peptides and proteins. CIII. Mass transfer resistances in ion-exchange and dye-affinity chromatography of proteins. AB - Adsorption equilibria and rate kinetics have been investigated for the binding of several proteins, with different molecular geometries, to several ion-exchange and dye-affinity chromatographic resins with varying pore size and protein accessibilities. The pore geometry was shown to play a significant role in the protein capacity and loadability of both the ion-exchange and dye-affinity resins. For example the Fractogel HW75-Cibacron Blue F3GA affinity sorbent had the greatest capacity for the small protein, lysozyme, compared to the other Fractogel HW-Cibacron Blue F3GA sorbents, and similarly, the ion-exchange resins, such as DEAE-Fractogel 65, bound more human serum albumin (HSA), as opposed to the larger protein, ferritin. The apparent diffusion of protein from the bulk phase to the ligands/ionic sites was calculated to be considerably restricted when the pore to protein size ratio was small, as is the case of DEAE Fractogel 65/ferritin system, and the dye-affinity Fractogel HW55/HSA system. In these circumstances, pore diffusivity was calculated to be up to 100-fold smaller than bulk diffusivity. PMID- 2229223 TI - High-performance liquid chromatographic approach to the separation of antiviral and immunostimulant fractions in Neuramide. AB - Neuramide, a tissue extract having antiviral action against influenza A virus and immunostimulant action, was analyzed by preparative size-exclusion high performance liquid chromatography (HPLC) and a low-molecular-weight fraction responsible for the antiviral action was isolated after reversed-phase HPLC. Four fractions having immunostimulant activity were also isolated, as evidenced by their potentiating action in the human lymphocyte proliferation induced by phytohaemagglutinin. PMID- 2229224 TI - Purification of immunomodulatory factors in human peripheral blood leukocytes. AB - Procedure is described for purifying low-molecular-weight factors with antigen aspecific properties from a dialysate of human leukocyte extract. It includes gel chromatography on Sephadex G-25 and G-15, ion-exchange chromatography, reversed phase high-performance liquid chromatography (HPLC) on a C18 hydrophobic column and gel permeation HPLC. The immunosuppressive factor (mol.wt. 800-1000) was purified to near homogeneity. It is probably of peptidic nature, although it is pronase resistant. The enhancer factor (mol.wt. 300-600) is eluted from chromatographic columns together with a hypoxanthine-like substance. Nevertheless, the biological activity cannot be attributed to the purine derivative. Identification of this amplifier activity is still lacking. PMID- 2229225 TI - Isolation of isoproteins from monoclonal antibodies and recombinant proteins by chromatofocusing. AB - A fast protein liquid chromatographic method for the preparative separation of the various isoproteins is described. Highly purified human monoclonal antibodies, recombinant human superoxide dismutase and human superoxide dismutase from erythrocytes were used as starting material. The isoproteins were separated by chromatofocusing on Mono P columns. A very narrow pH gradient was applied to achieve complete separation of the isoproteins. The prepurification steps and the pretreatment of the samples to achieve optimum resolution are described in detail. The method is also applicable to extremely basic monoclonal antibodies (pI = 9). The successful separation was checked by isoelectric focusing in immobilized pH gradients (Immobilines). The future of these methods is discussed, because for many different biochemical and biophysical investigations pure and homogeneous isoproteins are necessary. PMID- 2229226 TI - Separation of fragments from human serum albumin and its charged variants by reversed-phase and cation-exchange high-performance liquid chromatography. AB - Reversed-phase high-performance liquid chromatography (RP-HPLC) and ion-exchange chromatography on poly(2-sulphoethylaspartamide)-silica (SCX) were compared as alternative approaches in characterizing charged genetic variants of human serum albumin. The chromatographic behaviour of cyanogen bromide (CNBr), tryptic and V8 protease digests from normal and mutant albumins were examined. The results showed that substituted site-containing CNBr fragments are successfully resolved by RP-HPLC; in most instances SCX and RP-HPLC are equally adequate in identifying the modified tryptic peptides from CNBr fragments; although generally useful, SCX chromatography is specifically needed in all instances where amino acid replacement is occurring in a small hydrophilic tryptic fragment and choosing Staphylococcus aureus V8 protease instead of tryptic digestion is advantageous. PMID- 2229227 TI - Chromatography and generation of specific antisera to synthetic peptides from a protective Boophilus microplus antigen. AB - Four oligopeptides corresponding to predicted antigenic regions of the protective Bm86 glycoprotein of the cattle tick Boophilus microplus were synthesized and purified. Three were conjugated to carrier proteins and antisera raised in rabbits and cows. All elicited antipeptide antibodies that recognized Bm86 and recombinant derived products in Western blots; however, only one produced antiserum capable of recognizing native Bm86 in an indirect immunofluorescence assay. Ticks fed in vitro on this antiserum showed no obvious gut damage. PMID- 2229228 TI - Characterization of apolipoproteins from chicken plasma. AB - Although functionally similar, the lipoprotein systems of birds and mammals differ in composition. The major apolipoproteins, apo A-I and apo B, are common to all vertebrates; however apo A-II and apo E, functionally important components of mammalian lipoproteins, are absent from chicken plasma. Chicken apo A-I and apo B have been characterized, and several minor apolipoprotein components have been observed in electrophoretic patterns of chicken lipoproteins. In this study a single density gradient ultracentrifugation was used to isolate and subfractionate chicken lipoproteins into density classes. Isolated lipoproteins were delipidated with hexane-isopropanol (3:2). Apolipoproteins were then solubilized at pH 8.5 in 3 M guanidine hydrochloride and chromatographed on a 25 X 0.4 cm C4 reversed-phase column using 0.1% trifluoroacetic acid in a gradient of acetonitrile in water. Molecular weights estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and amino acid compositions were compared with those of apolipoproteins from other species in a search for functional similarities. Similarities in composition between the major chicken apolipoprotein and several human apolipoproteins were observed. PMID- 2229229 TI - Evaluation of factors which affect column performance with immobilized monoclonal antibodies. Model studies with a lysozyme-antilysozyme system. AB - Methods are described for the automated evaluation of affinity columns by frontal boundary analysis. These methods were used to evaluate the performance of immunoaffinity columns based on antilysozyme monoclonal antibody-lysozyme immunoaffinity system. This model system enabled the effects of (i) matrix activation and (ii) the density of immobilized antibody on the change in specific activity of immobilized antibody to be quantitatively assessed. Experimental data were accumulated with carbonyldiimidazole-activated Fractogel HW65F and Trisacryl GF2000 resins and cyanogen bromide-activated Sepharose 4B. An increase in the molar ratio between the concentration of the active groups on the activated matrix and the concentration of immobilized antibody ligands did not result in significant change in the specific activity of the immobilized antibody in the immunochromatographic system. However, increased antibody density with the Fractogel HW65F resin resulted in an increase in the apparent heterogeneity of antibody binding sites for lysozyme and a significant decrease in the specific activity of the immobilized antibody. Furthermore, data from size-exclusion studies with these immunoaffinity matrices demonstrated that at high antibody densities, the accessibility of the immobilized antibody was further decreased due to steric resistance as the antigen size increased. PMID- 2229230 TI - Reversed-phase high-performance liquid chromatographic separation of synthetic phosphopeptide isomers. AB - Selectively phosphorylated synthetic peptides corresponding to the human neurofilament protein middle-sized subunit, H-Lys-Ser-Pro-Val-Pro-Lys-Ser-Pro-Val Glu-Glu-Lys-Gly-OH, and its analogues were separated by reversed-phase high performance liquid chromatography of mixtures consisting of the non phosphorylated, the diphosphorylated and the two different monophosphorylated isomers. Application of the algorithm for the expected retention times to 4-9 amino acid-long peptide fragments revealed the correct elution order of the monophosphorylated isomers. According to circular dichroism studies, this elution order is also compatible with the possibility of induced conformational orientation on the surface of the bonded phase. Chromatographic analysis of the synthetic phosphorylation reaction indicates that the reaction rates of the two structurally different monophosphorylated peptides are similar, which is in contrast to the in vivo site-directed reaction. PMID- 2229231 TI - High-performance displacement chromatography-mass spectrometry of tryptic peptides of recombinant human growth hormone. AB - The combination of high-performance displacement chromatography with continuous flow fast atom bombardment (FAB)-mass spectrometry (MS) offers a means of overcoming the sample capacity limitations imposed by the low flow-rates tolerated in microbore systems employed for directly coupled liquid chromatography-MS. Displacement chromatography is performed at high concentrations with the same equipment and columns as typically used in chromatography at low concentrations. By using this mode of chromatography with a solution of cetyltrimethylammonium bromide as the displacer, the capacity of a reversed-phase column can be increased 50- to 100-fold for separation of a tryptic digest of biosynthetic human growth hormone. Despite the high load, the use of displacement chromatography allowed high-resolution separation of the complex mixture of eighteen major components. On-line analysis by continuous flow FAB-MS yielded high-quality spectra of these peptides and demonstrated that sharp, single-component bands can be obtained in this separation. Along with the major fragments, the chromatogram showed other peptides originating from protein variants in the sample, from non-specific cleavage in the enzymatic digest or from autolysis of trypsin. On-line analysis also allowed selective ion monitoring of the column effluent for individual peptides and confirmed the high efficiency and resolution obtained by preparative displacement separations on HPLC columns and equipment. PMID- 2229232 TI - Binding of sodium dodecyl sulphate to an integral membrane protein and to a water soluble enzyme. Determination by molecular-sieve chromatography with flow scintillation detection. AB - We have determined the binding of sodium dodecyl sulphate (SDS) to the human red cell glucose transporter (polypeptide, Mr 54,117) and to a water-soluble enzyme, N-5'-phosphoribosylanthranilate isomerase-indole-3-glycerol-phosphate synthase (PRAI-IGPS) from Escherichia coli (Mr 49,484). [35S]SDS was equilibrated with each protein on molecular-sieve chromatography at a series of SDS concentrations. The binding ratios of SDS to protein were determined by flow scintillation detection and automated amino acid analyses. Unexpectedly the glucose transporter, which is a transmembrane protein, bound about the same amount of SDS per gram of protein as did the enzyme. At 1.6 mM SDS, slightly below the critical micelle concentration (CMC) (1.8 mM) in the eluent, the binding ratio was 1.6 g SDS/g protein for both the glucose transporter and PRAI-IGPS. At 2.0 mM SDS (above the CMC) the glucose transporter showed a binding ratio of 1.7 g SDS/g protein. The corresponding value for the enzyme was about 1.5 g/g. The SDS glucose transporter complex seems to be more compact than the SDS-enzyme complex as judged by molecular-sieve chromatography and by SDS-polyacrylamide gel electrophoresis. Recent neutron scattering results have shown a protein-decorated triple-micelle structure for the SDS-PRAI-IGPS complex. Hypothetically, the more compact SDS-glucose transporter complex may therefore consist of a dual-micelle structure. The molecular-sieve gel beads bound considerable amounts of SDS. The SDS binding to the gel matrix and to the proteins increased with increasing SDS concentration up to at least 1.6-2.0 mM SDS. In the case of the water-soluble enzyme a shoulder was observed in the binding curve at 1 mM SDS, probably reflecting a change in the conformation of the complex. PMID- 2229233 TI - Synthetic antibody fragment as ligand in immunoaffinity chromatography. AB - The possibility that a fragment of an antibody molecule may interact with a protein antigen was tested by studying the binding properties of a thirteen residue synthetic peptide with an amino acid sequence similar to part of a hypervariable segment of a monoclonal antibody directed against lysozyme. Affinity adsorbents were prepared with this peptide and with non-related peptides as ligand. Non-specific interactions could be abolished by washing the column with 0.05 M sodium thiocyanate in 20 mM tris-HCl (pH 7.4). Lysozyme was only bound to the antilysozyme adsorbent and could be eluted with 1 M sodium thiocyanate. The results show that immunoaffinity chromatography with synthetic peptide ligands which mimic the antigen-binding site may be a useful tool in the selective purification of proteins. PMID- 2229234 TI - Isolation of anti-idiotypic antibodies by immunoaffinity chromatography on Affinichrom beads. AB - Anti-idiotypic antibodies are important regulators of the immune system but they are difficult to isolate and monitor. We have developed a technique for isolating specific auto-anti-idiotypic antibodies by high-performance immunoaffinity chromatography using immobilized autologous anti-tumor antibodies as the affinity ligand. The isolated anti-idiotypes demonstrated the ability to react with the original antitumor antibodies and inhibit their reactivity against autologous tumor cells. This technique can be used to monitor regulatory antibodies in cancer patients receiving immune modulation therapy. PMID- 2229235 TI - Characterization of temperature-sensitive cytidine triphosphate synthase mutations in bacteria by high-performance liquid chromatography. AB - Cytidine triphosphate (CTP) synthase catalyzes the last step in pyrimidine ribonucleotide synthesis, namely the formation of CTP from UTP, ATP, and glutamine. Mutants devoid of CTP synthase activity require cytidine for growth and have been designated pyrG in an obligate cdd background. Using a ts mutation blocked in the conversion of UTP to CTP at 43 degrees C, it was demonstrated that the conversion occurs by growing cells at 33 degrees C or below where UTP and CTP pools are normal. Growth at 43 degrees C shuts off the enzyme, while UTP accumulates and CTP is decreased significantly. By now feeding exogenous cytidine the CTP pool can be restored to the level found at the permissive temperature. Intracellular nucleoside triphosphates (CTP and UTP) were separated on a Partisil SAX10 cartridge, using a linear gradient of low buffer (7 mM ammonium dihydrogenphosphate, pH 3.8) to high buffer (250 mM ammonium dihydrogenphosphate, pH 4.5 with 500 mM potassium chloride). Nucleoside triphosphates were also separated after enzymatic conversion of UTP to CTP in solution by cell extracts using ion-pair reversed-phase chromatography on a C18 cartridge eluted with a mixture of 95% buffer A (25 mM ammonium dihydrogenphosphate with 1 mM tetrabutylammonium phosphate, pH 7.0) and 5% buffer B (15% aqueous acetonitrile). Using the two different separation techniques, it was possible to monitor the level of UTP and CTP inside cells as well as the enzymatic conversion of UTP to CTP by the enzyme CTP synthase. PMID- 2229236 TI - Convenient purification of tritylated and detritylated oligonucleotides up to 100 mer. AB - Oligomers from crude phosphoramidite synthesis mixtures have been purified by reversed-phased high-performance liquid chromatography by exploiting the chromatographic variables of stationary phase pore size, chain length, and gradient shape. Chromatography was performed on oligomers up to 100-mer with mobile phases containing triethylammonium acetate/acetonitrile mixtures. Convenient guidelines are offered to enrich or purify synthetic oligomers. Tritylated oligomers up to 25 bases in length are best purified on C8 or C18, 80 A columns with moderate strength mobile phases using a combination of isocratic delays and shallow gradients. For oligomers longer than 25-mer, C3, 300 A columns provide adequate fast purification in as little as 5 min, while 300 A, C8 columns with long, slow gradients gave substantially increased purity. Chromatography of detritylated oligomers requires a modified approach. Up to 25-mer they are best purified on 80 A, C18 columns with much lower organic concentrations and shallower gradients than those used for tritylated oligomers. Detrytilated oligomers greater than 25-mer can be enriched on both C3 and C8, 300 A columns using the same conditions described for shorter detritylated oligomers. PMID- 2229237 TI - Rapid separation, quantitation and purification of products of polymerase chain reaction by liquid chromatography. AB - The polymerase chain reaction (PCR), a new, powerful method for rapid enzymatic amplification of specific DNA fragments, has gained tremendous popularity in molecular biology. This paper describes the successful application of liquid chromatography to the analysis of products of the PCR. Efficient separation of both DNA restriction fragments and amplified PCR products were achieved in 10-12 min on a new ion-exchange column, DEAE-NPR, packed with 2.5-microns non-porous particles. The PCR products were quantitated with a reproducibility within 10%. Use of liquid chromatography was demonstrated for separation and quantitation of PCR products in amounts below those required for direct analysis by ethidium bromide gel electrophoresis or a Hoechst 33258 dye-based fluorescence assay. Liquid chromatography was also demonstrated to be effective for quick optimization of PCR procedures. PMID- 2229238 TI - High-performance liquid chromatography of amino acids, peptides and proteins. XCIX. Comparative study of the equilibrium refolding of bovine, porcine and human growth hormone by size-exclusion chromatography. AB - The equilibrium refolding of bovine, porcine and human growth hormone and ovine prolactin in guanidine hydrochloride has been investigated using high-performance size-exclusion chromatography (HPSEC). It was found that bovine and porcine growth hormones exhibited very similar refolding behaviour. However, the renaturation of human growth hormone followed a different pathway. In particular, the folding transition of human growth hormone occurred at 4.7 M guanidine hydrochloride compared to 3.8 and 3.5 M for the bovine and porcine molecules, respectively, and 3.5 M for ovine prolactin. The refolding mechanism of an internally clipped fragment derived from partial tryptic digestion, exhibited similar folding properties to the corresponding intact molecule. The internally clipped analogue existed as a relatively larger molecule under fully denaturing conditions. Reduction followed by carboxymethylation resulted in growth hormone molecules with significantly reduced stability and altered folding properties. The results have been correlated with differences in structure to further demonstrate the utility of HPSEC in the study of protein folding and stability. PMID- 2229239 TI - (S)-2-hydroxypropyl-beta-cyclodextrin, a new chiral stationary phase for reversed phase liquid chromatography. AB - (S)-2- and (R,S)-2-hydroxypropyl-beta-cyclodextrin have been bonded to silica gel and evaluated as stationary phases for reversed-phase liquid chromatography. Stationary phases also were prepared on two silicas having different pore sizes and surface areas. Dissimilarities were observed in enantiomeric selectivities between these columns and also between these and the native beta-cyclodextrin columns. With the exception of compounds 5 and 10, all other racemates reported here which have been successfully resolved on the new phases are enantiomers which have not been previously reported as separated on the beta-cyclodextrin stationary phase. In some cases, there were also differences in enantioselectivities observed between the (S)- and the (R,S)-hydroxypropyl-beta cyclodextrin phases on the same silica. The results are discussed in terms of the retention mechanism and compared to results reported earlier for beta cyclodextrin columns. PMID- 2229240 TI - Applications of high-performance liquid chromatography to quantitation of metabolites and enzymes of the patulin pathway from Penicillium patulum. AB - Conditions for extraction and high-performance liquid chromatographic (HPLC) analysis for fourteen of the patulin pathway metabolites from Penicillium patulum are described which allow quantitation of the metabolite content of cultures at hourly intervals. The HPLC analysis is more sensitive than gas-liquid chromatographic analysis and is more quantitative than thin-layer chromatographic analysis. Separations on a preparative column allow for the collection and identification of new metabolites. The column elution program can be varied to optimize analysis time for individual metabolites, allowing individual enzymes of the pathway to be assayed by following the conversion of substrate to product. Analysis of product formation in crude enzyme mixtures can be used to assay an enzyme in the presence of subsequent enzymes of the pathway and to establish the pathway reaction sequence. PMID- 2229241 TI - High-performance liquid chromatographic method for the comparison of tanning capacity of tannic acid batches used in the manufacture of pregnancy testing kits. AB - A high-performance liquid chromatographic (HPLC) method was developed for the quantitative comparison of various batches of tannic acid from the same manufacturer used to aid the binding of human chorionic gonadotropin to sheep erythrocytes in the manufacture of pregnancy testing kits. The tannic acids were separated by reversed-phase HPLC on a C18 column using gradient elution with aqueous methanolic eluents at low pH. A portion of the chromatogram corresponding to the compounds involved in the tanninisation process was integrated and a linear relationship was established between this peak area and tannic acid concentration. The correlation coefficient was greater than 0.993 even in the absence of an internal standard. Tanning capacity was evaluated on the basis of the amount of tannic acid which remained following incubation with a known quantity of erythrocytes. The application of this procedure to three batches of tannic acid is demonstrated. PMID- 2229242 TI - Separation and determination of lipophilic corticosteroids and benzothiazepin analogues by micellar electrokinetic chromatography using bile salts. AB - The separation of corticosteroids and benzothiazepin analogues by micellar electrokinetic chromatography (micellar EKC) was studied in comparison with capillary zone electrophoresis. The separation of these substances was not successful under neutral and alkaline conditions because they migrated with the same velocity as that of the electroosmotic flow. Micellar EKC with sodium dodecyl sulphate (SDS) solutions was also not successful because these substances migrated with almost the same velocity as that of the SDS micelle, owing to their high lipophilicity. The use of bile salts, which have a similar skeleton to corticosteroids, as the micellar phase permitted the separation of these substances with high theoretical plate numbers (150,000-350,000) within a short time (ca. 15 min). Sodium cholate was particularly useful. The effects of bile salt concentration, pH and the addition of methanol were investigated. Micellar EKC was also applied to the determination of the drug substances in tablets and cream using the internal standard method and to purity testing of drug substances and tablets. PMID- 2229243 TI - Use of M-series retention index standards in the identification of trichothecenes by electron impact mass spectrometry. AB - A method for the reliable identification of a series of trichothecenes as their trifluoroacetate esters in porridge flake samples is described. The esters were separated by gas chromatography and identified from their retention times relative to n-alkyl-bis(trifluoromethyl)phosphine sulphide (M-series) retention index standards and their electron impact mass spectra. The relative retention times offer an independent identification method by which the reliability of the identification can be improved. The mass spectra and the relative retention times were obtained from the same gas chromatographic-mass spectrometric run. Detection limits were of the order to 0.005-0.05 mg/kg. All the flake samples including oats (ten of fourteen samples studied) contained deoxynivalenol (0.01-0.2 mg/kg) and one oat flake sample contained HT-2 toxin (0.008 mg/kg). The other trichothecenes monitored were not found. PMID- 2229244 TI - Use of thin-layer chromatography for the testing of avermectins produced by Streptomyces avermitilis strains. PMID- 2229245 TI - Comparison of quarter-hourly on-line dynamic headspace analysis to purge-and-trap analysis of varying volatile organic compounds in drinking water sources. AB - On-line dynamic headspace analysis was refined for the quarter-hourly monitoring of select volatile organic compounds (VOCs) in ground and surface waters, for extended periods of time. Hourly comparisons were made to on-line purge-and-trap analysis, and to purge-and-trap analysis after sample preservation and storage. Variations in VOC concentrations of 6047% biweekly, 222% daily, 97% hourly, and 35% quarter-hourly were observable, with the 15-min cycle of the dynamic headspace analysis. The headspace analyzer had superior retention time stability, required less maintenance, and had 1/4 the analysis time as a typical purge-and trap-gas chromatograph system used for hourly comparisons. PMID- 2229246 TI - Simultaneous determination of neutral and amino sugars in biological materials. AB - A method is described for the simultaneous analysis of nine neutral and three amino sugars. Mixtures of standard sugars and biological samples were acid hydrolyzed with a two step Saeman procedure, neutralized with BaCO3, reduced with sodium borohydride, acidified, evaporated and alditol acetates prepared. Baseline resolution was achieved on a glass-capillary SP-2340 column in ca. 52 min. Reproducibility, response factors and hydrolysis losses were determined. Quantitation was linear over the range of 10-20 micrograms/ml to 2000 micrograms/ml. Conditions were defined for the reproducible quantitation of muramic acid. PMID- 2229247 TI - Molecular mass distribution of water-soluble crystallins from the human foetal lens during development. AB - The water-soluble crystallins of twenty human foetal lenses with gestational ages of 112-231 days were analysed by size-exclusion chromatography. The crystallin distribution showed similar patterns for all foetal lenses, but clear changes in the proportions of different crystallins were evident. The distribution showed that the water-soluble part of all the lenses already contained high-molecular mass material. Also beta-crystallins of high molecular mass (beta H), formed by post-translational changes, were detected in all stages. During gestation, the percentage of high-molecular-mass crystallins and of alpha-crystallins of low molecular mass (alpha L) decreased significantly. The total beta-crystallins (beta T) and the total gamma-crystallins (gamma T) increased significantly. The low Mr crystallins were resolved into three peaks, designated beta s-, gamma H- and gamma L-crystallins. They increased significantly during development. These significant increases of the low Mr crystallins took place exclusively in the developing lens. The rate of protein synthesis of the low Mr crystallins was 23% of the total water-soluble crystallin synthesis rate. PMID- 2229248 TI - High-performance liquid chromatographic analysis of bile pigments as their native tetrapyrroles and as their dipyrrolic azosulfanilate derivatives. AB - A reversed-phase high-performance liquid chromatographic (HPLC) analysis of bile pigments is described that provides baseline separation of the major bilirubin conjugates found in bile. The advantage of the technique is that the bile pigments can be analyzed directly as their native tetrapyrroles without prior solvent extractions or derivatization. The use of ammonium acetate in place of sodium salts permits preparative isolation and lyophilization of the pigments for mass spectroscopy. The derivatization of the pigments as their dipyrrolic azosulfanilates with subsequent HPLC analysis demonstrates baseline separation of the endo- and exovinyl azodipyrroles and allows identification of that half of the tetrapyrrole which contains the conjugate in the instances of monoglycosides. PMID- 2229249 TI - Determination of captopril in human blood by gas chromatography-negative-ion chemical ionization mass spectrometry with [18O4]captopril as internal standard. AB - A method for the quantitative measurement of captopril in human blood is described. Blood was immediately treated with N-ethylmaleimide to prevent oxidative degradation. The carboxyl moiety was derivatized to the pentafluorobenzyl ester, which shows excellent properties for negative-ion chemical ionization mass spectrometry. A stable isotope-labelled standard was prepared from the intact target molecule in quantitative yield by exchanging the oxygen atoms of the free carboxylic acid and the imide moiety against 18O. The detection limit under negative-ion chemical ionization conditions is ca. 100 times lower than under electron-impact or positive-ion chemical ionization conditions, therefore only very small amounts of the original sample have to be analysed. The method was applied to be quantitative determination of unchanged captopril in human plasma after oral administration of a 25-mg dose. PMID- 2229250 TI - Determination of metrifonate and dichlorvos in whole blood using gas chromatography and gas chromatography-mass spectrometry. AB - Analytical methods for determining metrifonate and dichlorvos in whole blood and a sampling procedure suitable for pharmacokinetic studies in man are described. Metrifonate concentrations were determined after chloroform extraction using gas chromatography-nitrogen-phosphorus detection. The within-assay coefficients of variation were 4 and 9% at 19.4 and 0.8 mumol/l (limits of determination), respectively. Dichlorvos was determined using gas chromatography-mass spectrometry of toluene extracts. The within-assay coefficients of variation were 2 and 5% at 225 and 50 nmol/l (limits of determination), respectively. Since both substances are chemically unstable, the blood was collected by dripping it directly from the vein into 0.74 M phosphoric acid. PMID- 2229251 TI - Determination of atracurium and laudanosine in human plasma by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method coupled with fluorometric detection has been developed for the determination of atracurium and its major end-product laudanosine in human plasma. The method enables good separation of atracurium from its metabolites after direct precipitation of plasma proteins. The assay is sensitive, reproducible and linear for atracurium concentrations ranging from 31.25 to 8000 ng/ml. In a clinical setting, drugs commonly administered during anesthesia did not interfere with the assay. This method provides a simple and time-saving alternative to existing methods. PMID- 2229252 TI - High-performance liquid chromatographic bio-analysis and preliminary pharmacokinetics of the experimental antitumour drug vintriptol. AB - A high-performance liquid chromatographic procedure, including sample pretreatment, is presented for the analysis of the experimental antitumour drug vintriptol in plasma. The sample pretreatment involved liquid-liquid extraction of the buffered (pH 3) sample with chloroform. Vinblastine was used as internal standard. Separation was achieved on a Hypersil ODS (5 microns) column with a mobile phase of acetonitrile-phosphate buffer. Electrochemical detection (at +0.70 V) was used, giving a detection limit of 2 micrograms/l. The applicability of the assay was demonstrated in a pharmacokinetic study with eight cancer patients who received 45 or 50 mg/m2 vintriptol in a phase I study. A three compartment model was used to fit the plasma concentration-time curves. Pharmacokinetic parameters are presented. PMID- 2229253 TI - Determination of the enantiomers of mefloquine in plasma and whole blood using a coupled achiral-chiral high-performance liquid chromatographic system. AB - A coupled achiral-chiral high-performance liquid chromatographic system has been developed for the determination of the enantiomers of mefloquine, (+)-MFQ and (-) MFQ, in plasma and whole blood. The MFQ was separated from the interfering components in the biological matrix and quantified on a cyano-bonded phase, and the enantiomeric composition was determined on an (S)-naphthylurea chiral stationary phase. The two columns were connected by a switching valve equipped with a silica precolumn. The precolumn was used to concentrate the MFQ in the eluent from the achiral column before backflushing onto the chiral phase. The coupled-column system was validated and applied to the analysis of a pilot study of the pharmacokinetics of (+)- and (-)-MFQ in plasma and whole blood. PMID- 2229254 TI - Simultaneous determination of disopyramide and its mono-N-dealkylated metabolite enantiomers in human plasma and urine by enantioselective high-performance liquid chromatography. AB - Enantiomers of disopyramide (DP) and its mono-N-dealkylated metabolite (MND) were determined in human plasma and urine by enantioselective high-performance liquid chromatography using a chiral stationary-phase column. This method was precise and sensitive: the mean recoveries from plasma at a concentration of 0.5 microgram/ml were 101.1% for (+)-DP, 98.0% for (-)-DP, 94.4% for (+)-MND and 82.9% for (-)-MND; the within- and between-day coefficients of variation at the same concentration were 4.4 and 3.3% for (+)-DP, 4.7 and 4.1% for (-)-DP, 6.5 and 4.1% for (+)-MND and 7.8 and 2.4% for (-)-MND for plasma; the lower detection limits were 40 ng/ml for (+)-DP, 80 ng/ml for (-)-DP, 100 ng/ml for (-)-MND and 200 ng/ml for (+)-MND, for 0.5 ml of plasma and 0.2 ml of urine. The ultrafiltration technique was used for determination of the unbound concentration of DP enantiomers in plasma. A preliminary study of the determination of DP and MND enantiomers in plasma and urine samples from a healthy subject given racemic DP demonstrated the clinical applicability of the present method for therapeutic monitoring and pharmacokinetic studies. PMID- 2229255 TI - Sensitive method for the determination of daunorubicin and all its known metabolites in plasma and heart by high-performance liquid chromatography with fluorescence detection. AB - The cytostatic agent daunorubicin is effective against leukaemia. An important side-effect is cardiomyopathy, common to all anthracyclines. Since anthracycline metabolites are thought to contribute to the observed cardiotoxicity, a method for the quantitative determination of all metabolites in plasma as well as in tissues is needed as a basis for the further investigation of the correlation between toxicity and the amount of each metabolite formed. Using Sep-Pak C18 cartridges we were able to extract daunorubicin and its five metabolites, including the aglycones, with recoveries in the range 50-90%. Depending on the chemical properties of each metabolite, fluorescence detection following high performance liquid chromatographic separation permitted detection limits as low as 0.2-0.9 nM in plasma and 0.8-3.10(-11) mol/g in tissue, at a signal-to-noise ratio of 2, which compare favourably with literature data. The method showed linearity in the ranges 1-250 nM in plasma and 0.04-4.0 nmol/g in tissue (r greater than or equal to 0.998). The accuracy determined at 10 and 100 nM for plasma and at 0.1 and 1.0 nmol/g for tissue, was in the range 86-103 and 85-110% for plasma and tissue, respectively. The within-day and between-day repeatability values were acceptable (between 2 and 12%). Because of large inter-compound differences, separate calibration curves were used for each anthracycline. Application of the assay to the analysis of plasma and tissue samples of mice after intravenous injection of daunorubicin proved successful. PMID- 2229257 TI - Rapid determination of urinary oxalate by high-performance liquid chromatography. PMID- 2229256 TI - Determination of a potential antiasthmatic compound, tibenelast, and its application to phase I clinical trials. AB - A sensitive and selective high-performance liquid chromatographic (HPLC) assay was developed for the determination of tibenelast, 5,6-diethoxybenzo[b]thiophene 2- carboxylic acid, in plasma and urine. The plasma assay involves protein precipitation with 4% trichloroacetic acid, while the urine assay is an automated solid-phase extraction procedure that utilizes the Waters Millilab workstation. The analysis was achieved by reversed-phase HPLC with ultraviolet detection at 313 nm. The quantitation limit of the assay was 50 ng/ml in plasma and 100 ng/ml in urine. The intra-day coefficient of variation for the plasma analysis was between 2.2 and 8.4%, while the overall inter-day coefficient of variation was 5.5 and 6.0% for the high and low calibration curves, respectively. The intra-day coefficient of variation for the urine analysis was between 0.3 and 3.0%, while the inter-day coefficient of variation was 2.1% for both the low and high validation samples. The assay methodology has been used in the evaluation of samples from pharmacokinetic and clinical safety studies. PMID- 2229258 TI - Measurement of acetylcholine and choline in cerebrospinal fluid by high performance liquid chromatography: failure to detect acetylcholine in normal human cerebrospinal fluid. PMID- 2229259 TI - Determination of gamma-aminobutyric acid in human cerebrospinal fluid by isocratic high-performance liquid chromatography. PMID- 2229260 TI - Separation of albumin-binding ligands present in uremic serum by high-performance affinity chromatography. PMID- 2229261 TI - New high-performance liquid chromatographic method for the determination of low activities of dihydropyrimidine dehydrogenase. PMID- 2229263 TI - Determination of alcuronium in plasma and urine by high-performance liquid chromatography. PMID- 2229262 TI - New assay method for the determination of vinpocetine in human plasma with gas chromatography-mass spectrometry without transesterification caused by solvents. PMID- 2229264 TI - High-performance liquid chromatographic analysis of unchanged cis diamminedichloroplatinum (cisplatin) in plasma and urine with post-column derivatization. PMID- 2229265 TI - Determination of the plasma protein binding of the coumarin anticoagulants phenprocoumon and its metabolites, warfarin and acenocoumarol, by ultrafiltration and high-performance liquid chromatography. PMID- 2229266 TI - Determination of tenilsetam in human plasma and urine by high-performance liquid chromatography. PMID- 2229267 TI - Sensitive one-step extraction procedure for high-performance liquid chromatographic determination of viloxazine in human plasma. PMID- 2229268 TI - Determination of denopamine in human and dog plasma by high-performance liquid chromatography with electrochemical detection. PMID- 2229269 TI - Quantitative determination of selected compounds in a Kentucky 1R4F reference cigarette smoke by multidimensional gas chromatography and selected ion monitoring-mass spectrometry. AB - Eight compounds from a Kentucky 1R4F reference cigarette smoke condensate have been determined by selected ion monitoring-mass spectrometry (SIM-MS) to confirm the validity of multidimensional gas chromatography (MDGC) as a quantitative tool in complex mixture analyses. Four electrostatically precipitated smoke condensate samples of 100 cigarettes each are dissolved individually in 25 mL of 2-propanol. The 2-propanol contains two methyl esters (C8 and C14) and seven deuterium labeled compounds used as internal standards (IS). Analysis of the compounds of interest, pyridine; acetamide; acrylamide; phenol; o-, m-, and p-cresol; and quinoline, is accomplished by using two heartcuts. Heartcut times of the MDGC analysis are selected such that at least one IS is transferred with each group of compounds being analyzed. This study shows that the MDGC technique previously developed and described can be used for quantitative analyses. A comparison is made between the two types of internal standards. The results obtained for both types of internal standards agree within 20% of each other, on the average, with higher standard deviations for approximately 60% of the compounds where methyl esters are used as internal standards. PMID- 2229270 TI - Separation and quantitation of monovalent anionic and cationic species in mainstream cigarette smoke aerosols by high-performance ion chromatography. AB - A simple method has been developed to separate and quantitate monovalent ionic species in mainstream cigarette smoke aerosols based on ion chromatography (IC) with conductivity detection. The method entails collecting the smoke aerosol particulate phase by electrostatic precipitation, dissolving the smoke condensate in methanol (MeOH), and separating the ionic species on either a cation- or anion exchange column. The method has been applied to the analysis of smoke aerosols from two cigarettes, 1R4F Kentucky Reference cigarettes and a new cigarette that heats but does not burn tobacco. The predominant cations in smoke aerosols from 1R4F Kentucky Reference and the new cigarettes are sodium (Na+), ammonium (NH4+), and potassium (K+) ions; the predominant anions are acetate (AcO-) and formate (HCOO-). Trace amounts of chloride (Cl-), nitrite (NO2-), and nitrate (NO3-) ions are also present. PMID- 2229271 TI - Clinical review 15: Management of ovulatory disorders with pulsatile gonadotropin releasing hormone. AB - Pulsatile GnRH therapy has yet to achieve widespread acceptance as an alternative to exogenous gonadotropin therapy in women with hypothalamic amenorrhea and complete GnRH deficiency. However, when a physiologically based replacement regimen of pulsatile GnRH is used, a high rate of ovulation and conception can be anticipated in patients with complete GnRH deficiency and hypothalamic amenorrhea. Women with polycystic ovarian syndrome may also benefit from pulsatile GnRH, although rates of ovulation are lower. Pretreatment with a GnRH agonist may improve these rates considerably, but experience is limited. Whether an iv or sc route of administration is chosen, a simplified clinical monitoring protocol can be created which requires a minimum of patient monitoring while assuring maximum safety. Seventy five nanograms per kg appears to be a reasonable initiating dose, with subsequent increases in those who do not respond. The frequency of GnRH administration is best based on the GnRH pulse frequency in normal women. However, further information is needed to determine whether such a variable frequency is clearly superior to a fixed frequency regimen. When used appropriately, pulsatile GnRH is safe, effective, and offers an excellent alternative to conventional gonadotropin therapy for women with disordered endogenous GnRH secretion. Most importantly, and as opposed to exogenous gonadotropin therapy, pulsatile GnRH can be administered by most physicians in the office setting without the necessity of on-line E2 monitoring. This feature will enable more patients to receive treatment by their local physicians, whereas exogenous gonadotropin therapy should be administered by appropriately equipped referral centers. In the future, further studies will be required to determine which other categories of patients might benefit from pulsatile GnRH. PMID- 2229272 TI - Attainment of peak bone mass. PMID- 2229273 TI - Effects of hormonal status on bone density in adolescent girls. AB - Few data are available on bone density in late adolescence. We studied factors affecting peak bone density in females. Forty-three white girls, aged 13-20 yr, were studied. Integrated estrogen exposure over the pubertal years was obtained by a score based on physiological events known to reflect circulation estrogen levels. The subjects were selected to provide great variation in estrogen exposure. Bone mineral density (BMD) was measured by single photon absorptiometry (midradius) and dual photon absorptiometry (spine and first metatarsal of the foot). Weight, estrogen score, and testosterone levels were highly correlated with BMD of the spine, wrist, and foot (P less than 0.05). Age correlated positively only with the BMD of the wrist. Twenty-four girls reaching ages 18-20 yr in the 2 yr of observation were divided into groups reflecting low (less than 24), medium (25-48), and high (greater than or equal to 49) estrogen exposure. The lowest scoring groups had the lowest spine and wrist BMD (P less than 0.05). This group weighed less and had lower weight to height ratio (P less than 0.05), the lowest weight (P less than 0.05) during adolescence, the highest age of menarche, and the highest amount of fiber in the diet (P less than 0.05). These subjects were separated into low and high BMD groups. Those subjects with the lowest values for spine, wrist, and foot were found to have significantly lower estrogen exposure scores and lower weight/height ratios; in addition, low BMD of the foot was associated with higher activity levels. Thus, wrist and spine BMD are affected by estrogen exposure during adolescence and weight; foot BMD, in addition, was negatively affected by activity, suggesting that bone mass in the active adolescent is affected by the absence of estrogen exposure. PMID- 2229274 TI - Immunological evidence for a human ovarian tumor necrosis factor-alpha. AB - Tumor necrosis factor-alpha (TNF alpha) was localized to follicular and luteal compartments of the human ovary using a biotin strept-avidin immunocytochemical technique with polyclonal antibodies to human recombinant TNF alpha. Immunoreactive TNF alpha (I-TNF) was observed in granulosa cells of healthy antral and atretic follicles and appeared to be secreted by the granulosa cells, since it was present in the follicular fluid surrounding antral and degenerating granulosa. Preantral follicles did not exhibit I-TNF. I-TNF was in the cytoplasm of large granulosa-lutein cells and small paraluteal cells. Granulosa cells cultured on an Immobilon membrane exhibited I-TNF in the cytoplasm and I-TNF released onto the membrane, which appeared as a dark-red stain after immunolocalization. Granulosa cells cultured on plastic slides exhibited I-TNF throughout the cytoplasm. To determine if I-TNF was secreted by granulosa cells, granulosa cell-conditioned medium was examined for the presence of TNF by a double sandwich enzyme-linked immunosorbant assay using both monoclonal and polyclonal antibodies to human recombinant TNF alpha. Conditioned medium contained up to 800 pg TNF/500,000 cells after 24 h of culture. I-TNF was also found (100-170 pg/mL) in human follicular fluid. Immunoblot assay of I-TNF in cultured granulosa revealed approximately 240 pg TNF/250,000 cells. The results indicate that the human ovary contains I-TNF, and thus, a paracrine and/or autocrine role of TNF in human ovarian follicular function seems likely. PMID- 2229275 TI - Parathyroid hormone-like peptide in normal and neoplastic human endocrine tissues. AB - PTH-like peptide (PLP) is produced by tumors commonly associated with hypercalcemia as well as nonneoplastic tissues and several endocrine glands and tumors. To characterize the distribution of PLP in human endocrine tissues and tumors, we localized PLP in formalin-fixed paraffin-embedded material using the avidin-biotin-peroxidase technique with polyclonal antisera. Among peptide hormone-producing tissues, PLP was identified in nontumorous adenohypophysis and pituitary adenomas; medullary thyroid carcinomas; normal, hyperplastic, and adenomatous parathyroids; adrenal medulla and pheochromocytomas; normal pancreatic islets; and endocrine tumors of pancreas, gut, and lung, including small cell carcinomas. In other endocrine tissues PLP was identified in nontumorous thyroid follicular epithelium, colloid nodules, and follicular neoplasms; normal adrenal cortex, adrenocortical adenomas, and carcinomas; nontumorous testicular Leydig cells; normal ovarian granulosa and thecal cells; an ovarian thecoma and a granulosa cell tumor; placental trophoblast; and decidua. These results demonstrate that PLP is localized in many normal and neoplastic endocrine cells, including those not known to influence extracellular calcium homeostasis. The presence of PLP in a variety of endocrine tissues suggests that it may play a local physiological role in the growth or function of endocrine cells. PMID- 2229276 TI - Reproducibility of growth hormone testing procedures: a comparison between 24 hour integrated concentration and pharmacological stimulation. AB - The purpose of this study was to compare the reproducibility of two approaches to the evaluation of GH secretion: the integrated concentration of GH (IC-GH), a physiological test of GH secretion, and pharmacological stimulation tests. IC-GH was determined in 40 poorly growing children twice within 4 weeks. The first and second IC-GH were highly correlated r = 0.859, P less than 0.001. One hundred and thirteen poorly growing children underwent pharmacological GH stimulation tests twice within 6 weeks. A moderate correlation was found between the first and second pharmacological test r = 0.524, P less than 0.01. Among the three pharmacological stimuli studied, clonidine (n = 81) had the highest reproducibility followed by arginine (n = 20), and insulin (n = 12). We conclude that IC-GH is more consistently reproducible than the GH response to repeated pharmacological stimulation. PMID- 2229277 TI - Thyroid hormones influences sex steroid binding protein levels in infancy: study in congenital hypothyroidism. AB - In order to test the hypothesis of a role of thyroid hormones on the circulating levels of sex steroid binding protein (SHBG) in children, SHBG levels were determined in 15 infants with congenital hypothyroidism at diagnosis and during the first 18 months of T4 therapy and in a separate group of 13 children with congenital hypothyroidism (7.1 +/- 0.5 yr, mean +/- SD), treated before 1 month of age, both during adequate L-T4 therapy and 4 weeks after withdrawing therapy. SHBG levels were significantly lower in hypothyroid infants than in controls (48.2 +/- 6.5 vs. 77.8 +/- 7.9 nmol/L; P less than 0.01), and significantly lower in infants with athyreosis compared to those with ectopic or eutopic glands (P less than 0.05). In patients with low values at diagnosis, SHBG increased rapidly and remained normal during LT4 therapy. After 1.5-18 months of treatment, a positive correlation (P less than 0.01) was found between SHBG, FT4, and FT3 levels. In older hypothyroid children, 4 weeks after withdrawal of therapy a significant (P less than 0.05) decrease in SHBG concentrations was observed. Analysis of these results as well as previous reports in adults, indicates that thyroid hormones influence SHBG concentrations in infants and children. This study also indicates that thyroid hormones may play a role in the physiological postnatal increase of SHBG. PMID- 2229278 TI - Short term treatment of acromegaly with the somatostatin analog octreotide: the first double-blind randomized placebo-controlled study on its effects. AB - Several studies suggest that the somatostatin analog octreotide, or SMS 201-995, may effectively reduce GH hypersecretion. However, no double blind, placebo controlled study has substantiated these findings. We present the results of a randomized double blind 14-day clinical trial with octreotide in 20 patients with acromegaly. The drug was given sc every 8 h and to the initial dose (50 micrograms) was added another 50 micrograms every other day up to 200 micrograms. GH levels, calculated as the mean values of 12 observations at hourly intervals during 0700-1800 h, and insulin-like growth factor-I (IGF-I) levels were significantly reduced during octreotide treatment. Responses varied from a reduction of 97% of the basal mean GH level to no significant reduction in 2 of 10 patients. There was a good correlation between the reduction of GH and IGF-I levels. The main side-effects were gastrointestinal and well tolerated. We found a spontaneous variation of daily mean GH and IGF-I levels (at 0700 h) in the placebo group, ranging from approximately 150% to 50% of the GH and 120% to 80% of the IGF-I levels noted on day 0. In patients treated with octreotide, the occurrence of GH rises between administration times suggests that it may be desirable to give octreotide every 6 h in some patients. PMID- 2229279 TI - Evaluation of the growth hormone-binding proteins in human plasma using high pressure liquid chromatography gel filtration. AB - A technique using high pressure liquid chromatography gel filtration was used to evaluate GH-binding proteins (BP) in human plasma; eluate was monitored for radioactivity in a gamma-detection system connected to a computer. Plasma (200 microL) was incubated with [125I]human (h) GH (200,000 cpm) at 4 C for 20 h. The main GH-BP (peak II) was well separated from free [125I]hGH (peak III) and from a higher mol wt complex (peak I), which was minor. In our control plasma, the specific binding of [125I]hGH to peak II BP (II-BP) was 32.2 +/- 0.6% of the radioactivity. Scatchard analyses indicate an association constant of 3.6-7.4 X 10(8) M-1 and a binding capacity ranging from 24-86 ng/mL for peak II-BP in five normal adult plasma samples. Peak I material, separated from plasma of boys with pubertal delay, bound hGH with a low affinity (3 x 10(6) M-1) and a very high capacity (2 micrograms/mL). In cross-linking experiments, peak I appeared as two proteins of 165 and 174 kD; these mol wt were much higher than that of peak II BP, previously estimated at 53,000. hGH complexed to peak II-BP remained fully immunoreactive with use of the anti-hGH antibodies of our assay. In plasma containing 10-20 micrograms/L hGH, the proportion of bound hormone (peak II) was 44.5 +/- 2.3%, whereas the amount of hGH in peak I was very low or undetectable. Specific binding of hGH to II-BP was lowest during the first year of life and highest in adulthood. No sex difference was found. I-BP is differentially regulated, since its binding activity was significantly lower in adults than in prepubertal children. Normal values for age should be taken into account to interpret GH-binding activity, particularly in children 2 yr of age or younger. Our GH binding assay offers important gains in terms of rapidity and resolution; it has permitted a clear separation and characterization of the two GH-binding components present in human plasma. PMID- 2229280 TI - Steroid hormone receptors in human adipose tissues. AB - Administration of glucocorticoid, estrogen, and progesterone is followed by changes in human adipose tissue distribution, morphology, and function. Therefore, specific receptors for these hormones were determined in different regions of human adipose tissue using ligand techniques, with separation of bound and free hormone by chromatography, absorption techniques, or isoelectric focusing, as well as protein quantitation with monoclonal antibodies against human estrogen and progesterone receptors. Furthermore, mRNAs were measured by solubilization hybridization technique with glucocorticoid, estrogen, and progesterone receptor cRNA probes for human receptors. Saturable specific cytosolic glucocorticoid binding was found. Quantitative analyses indicated more binding sites and mRNAs in intraabdominal than sc adipose tissue samples. In contrast, neither specific estrogen or progesterone binding, cytosolic or nuclear receptor protein, nor mRNAs for these receptors could be identified in abdominal, femoral, or omental adipose tissues. Parallel control experiments confirmed the presence of both estrogen and progesterone receptors in rat adipose tissues. It was concluded that while glucocorticoid receptors are clearly present in human adipose tissues, female sex hormone receptors are not present in quantities detectable with presently available methods. Effects of these hormones on human adipose tissue might, therefore, be mediated via a minute nondetectable quantity of receptors, the glucocorticoid receptor, or indirect mechanisms. PMID- 2229281 TI - Glucose and gluconeogenic substrate exchange by the forearm skeletal muscle in hyperglycemic and insulin-treated type II diabetic patients. AB - To determine the contribution of skeletal muscle to fasting hyperglycemia in noninsulin dependent type II diabetes (NIDDM), the forearm balance of glucose, lactate, and alanine was quantified in 25 control subjects, 21 hyperglycemic (blood glucose: 11.6 mmol/L), and 19 insulin-treated patients with NIDDM (blood glucose: 5.8 mmol/L). Forearm glucose uptake was similar in controls (4.6 +/- 0.6 mumol L-1 min-1) and in hyperglycemic diabetic patients (4.5 +/- 0.9 mumol L-1 min-1). In spite of this, in the diabetic patients lactate (5.1 +/- 0.8 mumol L-1 min-1) and alanine (2.6 +/- 0.4) release by the forearm was 3- and 2-fold higher than in the control group (lactate: 1.7 +/- 0.8, P less than 0.005; and alanine: 1.3 +/- 0.2, P less than 0.05, respectively). The ratio of lactate release to glucose uptake was 57% and 18% in diabetic and control subjects, respectively. Insulin administration did not affect either glucose uptake or the release of gluconeogenic substrates by the forearm. It is concluded that: 1) in fasting patients with NIDDM, glucose is taken up by the skeletal muscle in normal amounts but preferentially used nonoxidatively with lactate formation. This suggests that, although the muscle does not contribute directly to fasting hyperglycemia, it may play an indirect role through an increased delivery of glucose precursors; and 2) insulin-induced normoglycemia is maintained by mechanisms that do not involve the exchange of glucose and gluconeogenic substrates by the skeletal muscle. PMID- 2229282 TI - Decreased serum triiodothyronine is associated with increased concentrations of tumor necrosis factor. AB - Previous studies in laboratory animals have shown that tumor necrosis factor alpha (TNF) may alter thyroid function tests. To determine whether elevated serum TNF levels are associated with altered serum concentrations of T4, T3, free T4, rT3, and TSH, we measured these parameters in 29 nursing home residents with detectable serum TNF levels and compared the levels to those found in 36 patients with undetectable serum TNF levels. The 2 groups were matched for age, sex, clinical problems, use of medications, and nutritional status. Patients with detectable serum TNF levels had significantly lower serum T3 concentrations compared to those with undetectable levels [1.072 +/- 0.588 vs. 1.621 +/- 0.594 nmol/L (mean +/- SD); P less than 0.01]. Differences in other tests did not achieve statistical significance. Thyroid function tests were not significantly different when patients with detectable interleukin-1 alpha levels, another cytokine secreted during endotoxemia, were compared to those with undetectable levels. These observations taken together with the previous findings in laboratory animals suggest that some of the alterations in thyroid hormone levels seen in nonthyroidal illness are associated with elevated serum concentrations of TNF. PMID- 2229283 TI - Regulation of intracellular free calcium in human myometrial cells by prostaglandin F2 alpha: comparison with oxytocin. AB - The effects of prostaglandin F2 alpha (PGF2 alpha) on intracellular Ca2+ concentration ([Ca2+]i) and inositol phosphate (IP) generation in human myometrial cells were evaluated and compared to the effects of oxytocin. Basal [Ca2+]i levels were 146 and 153 nM in the absence and presence of 1 mM extracellular Ca, respectively. In Ca-containing medium, both PGF2 alpha and oxytocin significantly (P less than 0.01) increased [Ca2+]i over control values, eliciting half-maximal stimulation (ED50) at 4 and 1 nM, respectively. In Ca-free medium the potency of PGF2 alpha to raise [Ca2+]i was drastically reduced (ED50, 2 microM), whereas that of oxytocin remained the same, although maximal responses were markedly decreased. PGF2 alpha had no effect on total IP production in the concentration range that significantly raised [Ca2+]i. However, at a 100 times higher concentration (10 microM), PGF2 alpha produced a maximum 48% increase in total IP, with a rapid (15-30 s) rise in IP3 and IP2, followed by IP1. A similar increase in IP production was obtained when [Ca2+]i levels were raised by A23187 to the same level as that obtained with 10-50 microM PGF2 alpha. The effect of PGF2 alpha was dependent on extracellular Ca and could be suppressed by verapamil, but not by pertussis toxin, or phorbol ester. In contrast, the potencies of oxytocin to raise IP and [Ca2+]i were similar and independent of extracellular Ca2+, and could be suppressed by pertussis toxin and phorbol ester, but not by verapamil. These data provide evidence that in isolated human myometrial cells, PGF2 alpha and oxytocin trigger an increase in [Ca2+]i by different mechanisms. The action of PGF2 alpha depends on extracellular Ca2+, whereas oxytocin activates the G-protein-dependent phospholipase-C-IP3-Ca2+ signal-transducing pathway, complemented by the influx of extracellular Ca2+. PMID- 2229284 TI - Vasopressin and oxytocin responses to illusory self-motion and nausea in man. AB - Vasopressin and oxytocin are nonapeptides secreted from the neurohypophysis; increases in vasopressin are associated with nausea and vomiting in some, but not all, species. Our aim was to determine whether plasma vasopressin and oxytocin levels were altered in healthy volunteers who did or did not develop nausea during vection, an optokinetic stimulus which produces the illusion of self motion. Vection was produced by rotating a drum with an inner surface of black and white vertical stripes around the seated stationary subject. Gastric myoelectrical activity was recorded continuously throughout the experiment with electrodes positioned on the abdominal surface. Plasma samples were obtained before vection and after drum rotation stopped when nausea and tachygastria were present. Vasopressin and oxytocin were extracted from plasma and quantified by RIA. During vection six subjects reported nausea and developed gastric dysrhythmias; six other subjects had no nausea and remained in normal 3-cpm myoelectrical rhythms. Vasopressin and oxytocin values before vection were similar in each group of subjects. One minute after vection stopped, plasma vasopressin levels were significantly greater (P less than 0.05) in subjects experiencing nausea and tachygastrias (35.4 +/- 26.7 pmol/L) than in those without symptoms (2.7 +/- 0.47 pmol/L). Oxytocin levels were unchanged by either vection or nausea. It is concluded that 1) vasopressin, not oxytocin, neurons in the magnocellular-neurohypophyseal system are activated during vection-induced nausea and gastric dysrhythmias; and 2) illusory self-motion may be used safely to study the neuroendocrine responses to brain-gut interactions and nausea in man. PMID- 2229285 TI - Effects of transdermal estrogen replacement on parathyroid hormone secretion. AB - The effect of transdermal 17 beta-estradiol replacement on ionized calcium and PTH levels was examined in 15 postmenopausal women. After baseline studies in the fasting state, the effect of a calcium infusion on PTH levels was studied. Estrogen replacement resulted in a fall in fasting resting ionized calcium and a rise in PTH levels. After calcium infusion there was no change in the shape of the relationship between plasma calcium and PTH. The level of nonsuppressible PTH secretion was not altered. Transdermal estrogen did not alter basal vitamin D binding protein levels, 25-hydroxyvitamin D levels, or calcitriol levels. We conclude that the effect of transdermal estrogen replacement on PTH secretion is completely explained by the lowering of ionized calcium, causing a rise in PTH secretion. Thus, with this route of estrogen replacement, there is no necessity to postulate a direct effect of 17 beta-estradiol on the parathyroid gland. PMID- 2229286 TI - Estrogen preserves a normal intestinal responsiveness to 1,25-dihydroxyvitamin D3 in oophorectomized women. AB - Estrogen treatment improves calcium malabsorption induced by surgical or natural menopause, but the mechanisms involved are still under debate, with both increased production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and improved peripheral responsiveness to the steroid having been proposed. To address this issue, we studied the effect of short term administration of 1,25-(OH)2D3 (1 microgram/day for 7 days) on intestinal fractional absorption of 47Ca (47Ca FA) and vertebral bone density, measured by dual photon absorptiometry, in 14 premenopausal women (aged 31-50 yr) before and 6 months after oophorectomy. After surgery, patients were randomly allocated to a 6-month treatment with either conjugated estrogens (0.625 mg/day; n = 7) or placebo (n = 7). Oophorectomy caused a decrease in both basal 47Ca FA (-40.8 +/- 23.4%; P = 0.004) and vertebral bone density (-7.21 +/- 1.20%; P less than 0.001) in the placebo group. Estrogen replacement prevented these changes and increased basal serum 1,25 (OH)2D3 (+10.3 +/- 10.9%; P = 0.047), whereas a detectable but not significant decrease was observed in the control group (-8.8 +/- 10.5%; P = 0.07). Assessment of 47Ca FA before and after 1,25-(OH)2D3 administration revealed a similar degree of responsiveness to the steroid in the estrogen-treated women before and at the end of the study period (45.8 +/- 6.9% vs. 42.9% +/- 14.9% from basal, respectively; P = 0.142), but a blunted response to 1,25-(OH)2D3 was observed in the placebo group at 6 months (27.9 +/- 17.7%) compared to the result obtained before surgery (36.7 +/- 9.1%; P = 0.032). Multifactor analysis of variance revealed that the effects of estrogen and 1,25-(OH)2D3 on 47Ca FA were independent of basal serum 1,25-(OH)2D3 levels. On the other hand, calcitriol administration increased serum 1,25-(OH)2D3 to a similar extent before and 6 months after surgery in the placebo group (24.2 +/- 18.3% vs. 34.7 +/- 16.7% from basal, respectively; P = 0.484) as well as in the estrogen-treated women (34.2 +/ 17.2% vs. 26.6 +/- 15.45%; P = 0.302). The significant impairment of 1,25 (OH)2D3 stimulation of 47Ca FA in spite of increased levels of circulating 1,25 (OH)2D3 in the untreated women is suggestive of an end-organ resistance to the vitamin D metabolite in a hypoestrogenic condition, which can be prevented by hormone replacement, and supports the hypothesis of a vitamin D-independent action of estrogen on intestinal calcium absorption. PMID- 2229287 TI - Effect of central obesity on regulation of carbohydrate metabolism in obese patients with varying degrees of glucose tolerance. AB - It has been proposed that central obesity, by virtue of the enhanced lipolytic activity of abdominal adipose tissue, leads to higher plasma FFA concentrations, which, in turn, decrease both hepatic removal of insulin and insulin-stimulated glucose uptake by peripheral tissues. In short, the predicted consequences of abdominal obesity are elevations in circulating FFA and insulin levels as well as insulin resistance. The goal of this study was to evaluate the relationships predicted by the overall hypothesis; this study was carried out in 31 obese females, defined as having normal glucose tolerance (n = 12), impaired glucose tolerance (n = 8), or noninsulin-dependent diabetes mellitus (n = 11). Abdominal obesity was estimated by determining the ratio of waist to hip girth, fasting and postprandial plasma FFA and insulin concentrations were measured at hourly intervals from 0800-1600 h, and insulin-stimulated glucose disposal was quantified by the euglycemic hyperinsulinemic clamp technique. The first step in the postulated sequence of events to be tested was that the greater the WHR, the higher the total integrated plasma FFA response. The correlation coefficient between these two variables was 0.29, indicating that the results did not support the prediction. Furthermore, we could not demonstrate any relationship between the magnitude of the plasma FFA and insulin responses (r = 0.20; P = NS). However, there was a modest inverse relationship between height of circulating plasma insulin concentration and a decrease in insulin-stimulated glucose uptake (r = -0.43; P less than 0.03) in the group as a whole. On the other hand, when the three groups were analyzed individually, a significant inverse relationship was only seen in the control group (r = -0.67), and a direct relationship was actually seen in patients with impaired glucose tolerance (r = 0.88). Furthermore, when the mean responses for the variables in each of the three groups were compared, it was apparent that the postulated relationships between abdominal obesity, plasma FFA concentration, and insulin secretion and action were not present. Thus, the data presented do not support the hypothesis that differences in the degree of central obesity play an important role in regulation of plasma concentrations of either FFA or insulin or in modulation of insulin stimulated glucose uptake in the patients we studied. PMID- 2229288 TI - Primary hyperparathyroidism and severe hypercalcemia with low circulating 1,25 dihydroxyvitamin D. AB - We report a postmenopausal woman with primary hyperparathyroidism (PHPT) and severe hypercalcemia while her total calcium intake was more than 2 g daily. Despite a markedly elevated intact PTH level, her serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] level was low (17 pmol/L; 7 pg/mL). With reduced calcium intake, her serum calcium normalized, and 1,25-(OH)2D increased to 122 pmol/L (51 pg/mL). At the same time, intact PTH decreased to 32% of the initial value. PHPT may be associated with low circulating 1,25-(OH)2D levels. Furthermore, low 1,25-(OH)2D levels in PHPT may be due to a direct effect of severe hypercalcemia and be reversible with correction of hypercalcemia. PMID- 2229289 TI - Secretion of chorionic gonadotropin by cultured human pituitary cells. AB - To investigate the possibility that the human pituitary gland secretes CG, we used a highly specific, two-site, double monoclonal immunoradiometric assay to measure CG in the medium in which the dispersed cells of pituitary glands from human fetuses of 20-24 weeks gestation were cultured. The cross-reactivity of immunopurified human LH in the CG assay was less than 0.03%. LH was also measured by a double monoclonal immunoradiometric assay. Secretion of CG by the cultured fetal pituitary cells was readily detectable, although in gradually decreasing amounts, for the 11 days of culture. LH secretion paralleled CG secretion and was much greater in magnitude. Pituitary cells from female fetuses generally secreted more CG as well as more LH than those from male fetuses. Dilutions of the medium showed that the secreted CG exhibited parallelism with the CG standard. Chromatofocusing of the medium across a pH 6-9 gradient yielded several peaks of LH immunoreactivity between pH 6.5 and 8.5, but no peaks of CG. Chromatofocusing of the medium across a pH 3-7 gradient yielded peaks of CG, but not LH, between pH 4.0-5.5. These data indicate that CG immunoreactivity, distinct and separable from LH immunoreactivity, is secreted by the dispersed cells of fetal human pituitary glands. PMID- 2229290 TI - Studies of the mechanism by which androgens enhance mitogenesis and differentiation in bone cells. AB - Recently, we reported a direct effect of androgens on murine and human bone cells to stimulate bone cell proliferation and differentiation. To test whether this effect of androgenic steroids might be mediated by growth factors, we measured relative concentrations of insulin-like growth factor-I and -II (IGF-I and IGF II) and transforming growth factor-beta (TGF beta) in the conditioned medium from androgen-treated murine calvarial cell cultures. Only the concentration of TGF beta was increased. Consistent with the increased secretion of TGF beta in the mouse calvarial cell system, we observed an increased expression of TGF beta mRNA in a normal human osteoblastic cell system. We also determined whether androgens alter the response to growth factors. We found that dihydrotestosterone (DHT) treatment enhanced the mitogenic effects of fibroblast growth factor (FGF) and IGF-II but not those of IGF-I. The enhanced effect of FGF and IGF-II after DHT pretreatment was not affected by addition of TGF beta-blocking antibodies or by changing the culture medium. This indicated that in addition to increased release of TGF beta, another mechanism might be involved in the action of DHT on human and murine bone cells. Thus, we investigated the binding of human IGF-II to human osteoblastic cells and observed an increase in IGF-II binding after DHT treatment. Our results are consistent with a mechanism of action of androgens on bone cells that involves the induction of TGF beta and, in addition, may sensitize the cells to show an enhanced response to FGF and IGF-II, possibly by changing the receptor binding of mitogenic growth factors. PMID- 2229291 TI - Sex differences in serum luteinizing hormone and testosterone in the human neonate during the first few hours after birth. AB - Blood was obtained from human male and female neonates within a few minutes after birth, and at intervals thereafter for up to 21 h. Serum LH was substantially higher at birth for boys than girls. For most boys, serum LH fell precipitously during the next hour; serum LH remained low for the remainder of the period sampled in both boys and girls. In girls, serum testosterone was low at birth and remained low for at least 21 h. At birth, serum testosterone in boys was higher than for girls, increased dramatically during the first 3 h after birth, and remained elevated (2 to 3 times higher than for girls) between 3 and 12 h after birth. In newborn human males, a sudden discharge of hypophyseal LH appears to stimulate neonatal secretion of testosterone by the testes. The functional significance of this phenomenon remains to be determined. PMID- 2229292 TI - Increased overnight growth hormone concentrations in diabetic compared with normal adolescents. AB - To determine the extent to which spontaneous plasma GH concentrations are abnormal in adolescents with insulin-dependent diabetes mellitus we performed 12 h overnight plasma GH profiles in 21 diabetic adolescents (11 males and 10 females; aged 9.8-16.5 yr; median, 13.6 yr) and 34 healthy adolescent controls (17 males and 17 females; aged 9.1-20.9 yr; median, 13.1 yr). Data were analyzed using the pulse detection program Pulsar and time series analysis, and are presented with respect to age and puberty stage. Mean and maximum GH concentrations, sum of the peak amplitudes, and mean calculated baseline concentrations in the normal children were higher during puberty; highest levels were seen in girls at puberty stages 2-3, and in boys at stages 4-5. A similar pattern was observed in the diabetic adolescents, but all measures of pulse height and mean calculated baseline concentrations were significantly greater than those in the normal subjects (multivariate analysis, P less than 0.001). Pulse frequency did not change during puberty in the normal or diabetic subjects, and the dominant pulse periodicity in both groups was about 180 min. We conclude that the predominant change in GH release during puberty is in pulse amplitude, and that this is increased in diabetes, whereas pulse frequency remains constant in both normal and diabetic adolescents. PMID- 2229294 TI - Corticotropin-releasing hormone inhibition of growth hormone-releasing hormone induced growth hormone release in man. AB - Recent studies in the rat have shown that intracerebroventricular administration of CRH inhibited spontaneous pulsatile GH secretion and prevented GH-releasing hormone (GHRH)-induced GH release. We have studied the effect of CRH on GHRH induced GH release in man. In the first study, CRH was injected iv at three different doses (100, 50, or 25 micrograms) at 0800 h together with 50 micrograms GHRH in six men and six women. In a second study, 100 micrograms CRH were given iv at 0800 h, 1 h before the administration of 50 micrograms GHRH in five men and five women. Each subject demonstrated a normal GH response after the administration of 50 micrograms GHRH plus saline. All doses of CRH administered simultaneously with GHRH significantly inhibited GHRH-induced GH release in women [peak value +/- SE after GHRH plus saline, 28.9 +/- 2.9 micrograms/L; after GHRH plus 100 micrograms CRH, 9.9 +/- 0.7 micrograms/L (P less than 0.001); after GHRH plus 50 micrograms CRH, 8.7 +/- 0.8 micrograms/L (P less than 0.001); after GHRH plus 25 microgram CRH, 9.5 +/- 1.6 microgram/L (P less than 0.001]). In contrast, in men, while a dose of 100 micrograms CRH was capable of suppressing GHRH induced GH secretion (peak value +/- SE, 8.1 +/- 0.6 vs. 20 +/- 2.9 micrograms/L; P less than 0.001), no inhibition was observed after 50- and 25-micrograms doses. When 100 micrograms CRH were injected 1 h before the administration of 50 micrograms GHRH, it strongly inhibited GHRH-induced GH secretion in both men (peak value +/- SE, 6.2 +/- 2.8 vs. 24.6 +/- 5.9 micrograms/L; P less than 0.02) and women (peak value +/- SE, 14.2 +/- 4.5 vs. 37.8 +/- 6.7 micrograms/L; P less than 0.005), and this inhibition lasted up to 2 h post-CRH administration. These results demonstrate that CRH is capable of inhibiting GHRH-induced GH release in both men and women. Furthermore, the findings suggest that a sexual dimorphism in the neuroregulation of GH secretion may be present in man. In view of the inhibitory action of CRH on GH secretion, simultaneous administration of CRH and GHRH for testing should be avoided in clinical practice. PMID- 2229293 TI - Human follicular fluids contain tissue macrophages. AB - Tissue cells obtained from the follicular fluids of women undergoing in vitro fertilization and embryo transfer were found to contain interleukin-1 beta mRNA by Northern analysis. Since macrophages are known to produce interleukin-1 beta, we examined the follicular fluids of 20 women undergoing in vitro fertilization as well as tissue sections of normal human ovary for the presence of macrophages and monocytes. Although granulosa-luteal cells predominate in follicular fluid, we found that resident macrophages and monocytes comprise 5-15% of human follicular tissue cells. In addition, we observed that macrophages are present in the human ovarian follicle as well as in the corpus luteum. PMID- 2229295 TI - Levels of steroid-binding proteins and steroids in human preovulatory follicle fluid and serum as predictors of success in in vitro fertilization-embryo transfer treatment. AB - In an attempt to identify the embryos and cycles that have the best chances of resulting in establishment of pregnancies, after in vitro fertilization-embryo transfer (IVF-ET) treatment, the concentrations of sex hormone-binding globulin (SHBG) and cortisol-binding protein (CBP) were measured, using two new enzyme linked immunosorbent assays in serum and follicle fluid (FF) from 30 women (125 FF) undergoing IVF-ET. The concentrations were compared to those of total estradiol and total progesterone, and correlated to oocyte cleavage and the establishment of pregnancies. Serum concentrations of CBP were significantly higher in women who became pregnant (1469 +/- 108) nM (+/- SEM] than in those who did not (CBP, 1200 +/- 58 nM; P less than or equal to 0.05). The concentrations of SHBG were not significant different in these two groups of women (72.4 +/- 9.3 and 60.8 +/- 4.2 nM, respectively; P greater than or equal to 0.10). By contrast, in FF significantly higher concentrations of both SHBG and CBP were found in women achieving pregnancy (SHBG, 56.1 +/- 2.8 nM; CBP, 1198 +/- 37 nM) than in those who did not (SHBG, 45.5 +/- 1.4 nM; P less than or equal to 0.001; CBP, 1079 +/- 29 nM; P less than or equal to 0.01). A positive correlation was found between serum and FF levels of both SHBG (r = 0.85; P less than or equal to 0.001) and CBP (r = 0.70; P less than or equal to 0.001). FF levels of estradiol and progesterone did not differ regardless of whether the oocyte cleaved. However, a significant reduction of estradiol was found in fluid from follicles in which the oocyte cleaved and resulted in pregnancy (3046 +/- 180 nM) than in fluid from follicles in which the oocyte cleaved but without establishment of pregnancy (4162 +/- 282 nM; P less than or equal to 0.001). There was no correlation between estradiol and SHBG and between progesterone and CBP. However, levels of FF progesterone above 15,000 nM combined with CBP concentrations above the mean concentration found in FF (1,127 nM) were related with oocyte cleavage in 87% of the cases. The overall cleavage rate is 56%. The higher levels of SHBG and CBP in serum compared to those in FF, and the positive relationship between serum and FF levels suggest that both proteins arise from the circulation. The similar levels in serum and FF indicate that neither SHBG nor CBP is responsible for maintaining the concentration gradient of estradiol and progesterone from follicle to plasma.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2229296 TI - Influence of estrogens on serum free fatty acid levels in women. AB - A relationship between plasma levels of FFA and incidence of hormone-dependent breast cancer has been suggested. This observation has drawn our attention to possible complementary actions of ovarian steroids on circulating FFA levels. Measurements taken in normal women during the menstrual cycle and in ovariectomized women with and without estrogen replacement therapy demonstrate that 1) levels of FFA present in serum are lower during the luteal phase than during the follicular phase; 2) levels of FFA are significantly higher after ovariectomy; and 3) these are again reduced by substitutive estrogen therapy. PMID- 2229298 TI - Charles-Edouard Brown-Sequard and the centennial of endocrinology. PMID- 2229297 TI - Recombinant human activin-A promotes proliferation of human luteinized preovulatory granulosa cells in vitro. AB - Ovarian granulosa cells synthesize and secrete activin, a member of the transforming growth factor-beta (TGF-beta) peptide family, during the follicular phase of the menstrual cycle. We examined the growth-promoting activity of human recombinant activin-A on human luteinized preovulatory granulosa cells obtained from women undergoing in vitro fertilization. Activin-A induced proliferation of granulosa cells on day 5 of culture in a dose-dependent manner. Maximal effects were seen at concentrations greater than or equal to 100 ng/mL with an ED50 of 15 ng/mL. We suggest that activin-A is able to modulate growth of ovarian granulosa cells. PMID- 2229299 TI - Androgens, estrogens, and sex hormone-binding globulin in middle-aged men. AB - Although the administration of estrogens and androgens can affect the concentrations of sex hormone-binding globulin (SHBG) in men, the relationships between endogenous estrogens and androgens and SHBG are uncertain. Therefore, in a randomly selected cohort of 1640 middle-aged men we measured androgen, estrogen, and SHBG concentrations and obtained the subjects' weight, ethanol intake, and smoking histories. The data were analyzed by stepwise multiple regression, with SHBG as the dependent variable, to compare the role of hormones with that of other factors in the control of SHBG levels. Neither estrone or estradiol nor the testosterone/estradiol ratio was predictive of SHBG levels. However, SHBG concentrations were positively correlated with total testosterone and negatively correlated with percent free and percent albumin-bound testosterone. SHBG concentrations were negatively correlated with estrone sulfate, but were positively correlated with the testosterone/estrone sulfate ratio and the concentrations of free and albumin-bound testosterone. In addition, in all models tested age and body mass index (wt/ht2), but not smoking or ethanol, were strong predictors of SHBG concentrations. Thus, when present in physiological amounts in the blood as a result of glandular secretion, there is a positive relationship between SHBG concentrations and testosterone and, to a lesser extent, free- and albumin-bound testosterone, but age and body mass index appear to be more important in predicting the SHBG concentration. PMID- 2229300 TI - Association of fasting glucose levels with a delayed secretion of insulin after oral glucose in subjects with glucose intolerance. AB - Two hundred and nineteen second generation Japanese-American men were classified with a 75-g oral glucose tolerance test: 77 with normal glucose tolerance, 74 with impaired glucose tolerance (IGT), and 68 with noninsulin-dependent diabetes mellitus (NIDDM). The peak insulin response to the oral glucose load was progressively delayed with each of the 3 glucose tolerance categories. A similar finding was observed with the peak C-peptide response to oral glucose, except for the absence of distinction between IGT and NIDDM. Variables measuring the initial rate of insulin or C-peptide secretion (0-30 min) after oral glucose also demonstrated a progressive diminution with increasing glucose intolerance. The relative incremental insulin response at 30 min and the relative incremental C peptide response at 30 min were highly correlated with the fasting glucose levels (r = -0.61 and r = -0.62; P less than 0.0001, respectively). Variables measuring the 0-30 min secretory response had high variances, whereas the variance for fasting glucose was low. Twelve men who were initially classified as IGT subsequently developed NIDDM. These 12 men had significantly higher fasting glucose levels at baseline than the remaining men who did not develop diabetes, but the 30 min secretory parameters after oral glucose, although lower in those who subsequently developed diabetes, were not significantly different at baseline. However, if fasting glucose is used as a surrogate measure of secretory response, these 12 men appear to have had an impairment of oral glucose stimulated insulin secretion antedating the development of NIDDM. The inability of the secretory parameters to detect the abnormality may be due to a type II statistical error, which may be resolved by a larger sample size. PMID- 2229301 TI - Alterations in aldosterone secretion and metabolism in low renin hypertension. AB - Low renin essential hypertensives (LRH) have normal plasma aldosterone levels which are inappropriately high in relation to their PRA. Posture is the major determinant for plasma aldosterone and PRA levels, but it is not known whether postural increments (delta) of plasma aldosterone and (delta) PRA are also abnormal in LRH. To evaluate this, LRH (n = 8), normal renin hypertensives (NRH; n = 9), normotensive controls (n = 18), and subjects with idiopathic hyperaldosteronism (IHA; n = 5) were studied in a metabolic unit on a controlled diet over 7 days. Overnight supine and 4-h upright PRA, plasma aldosterone, and 24-h urinary tetrahydroaldosterone (THA) and aldosterone secretion rates (ASR) were measured. The delta in plasma aldosterone after 4 h of upright posture was not different in the four groups. The ratio of delta plasma aldosterone/delta PRA, however, was elevated in both IHA and LRH compared to that in NRH and normals. THA excretion was also elevated in IHA and LRH, but LRH had a normal ASR. This resulted in a higher fractional THA excretion (THA/ASR) in LRH compared to the other three groups. These data further support enhanced adrenal angiotensin-II sensitivity in LRH. Aldosterone was preferentially metabolized to THA in LRH. Since THA has reduced biological activity, this may be a compensatory mechanism to reduce mineralocorticoid activity in LRH. PMID- 2229302 TI - Comparative study of the changes in insulin-like growth factor-I, procollagen-III N-terminal extension peptide, bone Gla-protein, and bone mineral content in children with Turner's syndrome treated with recombinant growth hormone. AB - Six girls (7-13 yr old) with Turner's syndrome and short stature were treated for 1 yr with recombinant human GH (0.15 U/kg.day, sc) and had sequential determinations of serum insulin-like growth factor-I (IGF-I), osteocalcin, and procollagen-III. Bone mineral content and density of the spine and radius were measured before treatment and at 90 and 360 days. Two girls received small doses of ethinyl estradiol (0.025 micrograms/kg) in addition to GH. Height velocity increased by 144% after 3 months of treatment. IGF-I was normal (0.75 +/- 0.20 kU/L) before treatment and increased by 90% on day 1 and by 290% on day 360. Procollagen-III was low before treatment; it peaked at 53.0 +/- 14.7 micrograms/L (260% above baseline) on day 30, then decreased to the normal range. Serum osteocalcin increased more slowly to reach a plateau on day 90 of 23.7 +/- 1.2 micrograms/L (46% above baseline). Before treatment, bone mineral content of the spine was 25% lower than that of children matched for bone age. Bone mineral contents of the peripheral and axial skeleton were increased by 10% and 17%, respectively, after 1 yr of treatment, an increase commensurate with that of bone age in the four patients who did not receive estrogen. On day 90, however, although radius mineral density was already increased by 3%, the mineral density of the lumbar spine was significantly decreased by 4%. We conclude that treatment with GH increases IGF-I, collagen turnover, osteoblastic function, and height velocity in Turner's syndrome. However, there is no catch-up of bone mineral content after 1 yr of treatment, and an early effect of GH is to decrease spine mineral density. PMID- 2229303 TI - Influence of physical activity on insulin-like growth factor-I in healthy younger and older men. AB - To examine the hypothesis that a lower level of physical activity influences the age-related decline in insulin-like growth factor-I (IGF-I), we measured serum concentrations in healthy nonobese younger and older men, characterized for maximal aerobic capacity (VO2 max) and energy expended in leisure time physical activity. To examine the independent influence of physical activity on IGF-I relative to other lifestyle variables, we also determined fat-free weight, percent body fat, body fat distribution (waist to hip and waist to thigh ratios), and habitual caloric intake in our population. IGF-I was 33% lower (P less than 0.01) in older men than in younger men, inversely related to percent body fat (r = -0.55) and indices of upper body fat distribution (waist to hip ratio, r = 0.45; waist to thigh ratio, r = -0.47), and positively related to VO2 max (r = 0.64) and leisure time physical activity (r = 0.45; P less than 0.01). IGF-I was not related to fat-free weight or daily caloric intake. After controlling for the effects of age by multiple regression analysis, VO2 max (r = 0.29) and leisure time physical activity (r = 0.24) were the sole factors independently related to IGF-I (P less than 0.05). Our results suggest that multiple factors contribute to the age-related decline in IGF-I. Lower levels of IGF-I in aging men are related at least in part to diminished physical activity. PMID- 2229304 TI - Growth hormone (GH) responsiveness to combined administration of arginine and GH releasing hormone does not vary with age in man. AB - At present, the mechanism(s) underlying the reduced spontaneous and stimulated GH secretion in aging is still unclear. To obtain new information on this mechanism(s), the GH responses to both single and combined administration of GH releasing hormone (GHRH; 1 microgram/kg iv) and arginine (ARG; 30 g infused over 30 min), a well known GH secretagogue probably acting via inhibition of hypothalamic somatostatin release, were studied in seven elderly normal subjects and seven young healthy subjects. Basal GH levels were similar in both groups, while insulin-like growth factor-I levels were lower in elderly subjects (76.7 +/ 9.2 vs. 258.3 +/- 29.2 micrograms/L; P = 0.01). In aged subjects GHRH induced a GH increase (area under the curve, 314.9 +/- 91.9 micrograms/L.h) which was lower (P = 0.01) than that in young subjects (709.1 +/- 114.4 micrograms/L.h). On the other hand, the ARG-induced GH increase in the elderly was not significantly different from that in young subjects (372.8 +/- 81.8 vs. 470.6 +/- 126.5 micrograms/L.h). ARG potentiated GH responsiveness to GHRH in both elderly (1787.1 +/- 226.0 micrograms/L.h; P = 0.0001 vs. GHRH alone) and young subjects (2113.0 +/- 444.3 micrograms/L.h; P = 0.001 vs. GHRH alone). The potentiating effect of ARG on the GHRH-induced GH response was greater in elderly than in young subjects (1013.0 +/- 553.5% vs. 237.9 +/- 79.1%; P = 0.0001); thus, the GH increase induced by combined administration of ARG and GHRH overlapped in two groups. In conclusion, these results show that, differently from the GHRH-induced GH increase, the somatotroph response to combined administration of ARG and GHRH does not vary with age. Our finding suggests that an increased somatostatinergic activity may underlie the reduced GH secretion in normal aging. PMID- 2229305 TI - Impaired growth hormone (GH) response to pyridostigmine in type 1 diabetic patients with exaggerated GH-releasing hormone-stimulated GH secretion. AB - In the present study we investigated the effects of the acetylcholinesterase inhibitor pyridostigmine (PD), which is hypothesized to decrease hypothalamic somatostatin tone, alone and in association with GH-releasing hormone (GHRH) on GH secretion in 18 type 1 diabetic patients and 12 normal subjects using a randomized double blind placebo-controlled protocol. All subjects received either 120 mg oral PD or placebo 60 min before iv injection of either human GHRH-(1-29) NH2 (100 micrograms) or sterile water (2 mL). In normal subjects both PD alone and GHRH alone caused a significant increase in GH. PD and GHRH acted in a synergistic fashion when combined. In diabetic patients the GH response to GHRH was variable. To segregate the responses, the ratio between the GH increase after GHRH plus PD and after GHRH alone was calculated for each subject. In 10 diabetic patients (group A) the ratio was lower than 2 SD (P less than 0.05) from the mean response of normal subjects. These patients showed an exaggerated GH increase after GHRH and a lower GH increase after PD with respect to normal subjects. Eight diabetic patients (group B) showed a ratio similar to that in normal subjects and similar GH responses to the stimuli. No significant differences were found between groups A and B with respect to age, body mass index, and blood glucose levels. Duration of diabetes was longer and basal GH levels were higher in group A. Hemoglobin-A1c was higher in group A, but of only borderline statistical significance (P = 0.052). Our data demonstrate that in diabetic patients with exaggerated GH responses to GHRH an increase in cholinergic tone does not affect GH secretion. These data suggest that in some type 1 diabetic patients an altered somatostatinergic control of GH secretion may contribute to their abnormal GH response to GHRH. PMID- 2229306 TI - Adrenal medullitis in type I diabetes. AB - To investigate whether cell-mediated immunity against the adrenal medulla occurs in type I diabetes (IDDM), we conducted a retrospective autopsy study of adrenal glands from IDDM and nondiabetic subjects using formalin-fixed tissue. Forty-four IDDM subjects, aged 4-67 yrs (mean +/- SD, 44.8 +/- 15.4) with a duration of IDDM from 0-55 yr (28.6 +/- 14.2), and 29 nondiabetic controls, aged 8-82 yr (51.8 +/- 18.6), were evaluated for a lymphocytic infiltrate using UCHL1, which recognizes a subpopulation of resting T-lymphocytes and most activated T-lymphocytes. Immunohistochemistry using antihuman B-cell antibody (L26) was also performed. Sections were scored for both lymphocytic infiltrates and fibrosis [none (0), small (1), moderate (2), or large (3)]. Blinded scoring was performed. A moderate to severe UCHL1 infiltrate was present in 9 of 44 (20%) IDDM, compared with 1 of 29 (3%) control subjects (P less than 0.04). Mild to severe fibrosis (score 1, 2, or 3) was present in 22 of 42 (52%) IDDM subjects compared with 4 of 25 (16%) control subjects (P = 0.003). Eight of 42 (19%) IDDM subjects had moderate to severe fibrosis (score 2 or 3) compared with 1 of 25 (4%) control subjects. Seventeen of 44 (39%) IDDM subjects had either a moderate to large cellular infiltrate or moderate to severe adrenal medullary fibrosis compared with 2 of 29 (7%) control subjects (P = 0.003). Staining of the adrenal medulla with L26 revealed a large cellular infiltrate in only one subject who was UCHL1 negative. Adrenal medullitis was observed in 20% of IDDM subjects, suggesting that the adrenal medulla may be another immunological target in IDDM. PMID- 2229307 TI - Urinary human growth hormone measurement using a highly sensitive sandwich enzyme immunoassay: diagnostic and therapeutic uses in patients with growth hormone deficiency. AB - Several reports indicate that urinary hGH excretion is significantly lower in patients with either partial (PGHD) or complete GH deficiency (CGHD) than in normal but short children (NSC) or normal children (NC). However, there is an overlap between the NSC and NC groups and the PGHD group. Using a highly sensitive sandwich enzyme immunoassay, we investigated whether the measurement of urinary hGH can clearly separate the PGHD and CGHD groups from the NSC and NC groups. In addition, we measured the urinary excretion of synthetic methionyl-hGH (met-hGH) in PGHD and CGHD after sc injections of 2 and 4 IU and im injections of 4 IU in an attempt to determine the optimal replacement dose. Total 24-h urinary hGH excretion in each patient examined for 2 consecutive days varied from 1 day to the next. There were no differences in urinary hGH excretions between the NSC group and the NC group. The lower values for daily urinary hGH excretion in the NSC group overlapped some of the higher values in the PGHD group. However, when the mean urinary hGH level of both days was used, the 24-h urinary hGH excretion clearly separated the PGHD (5.5 +/- 2.3 ng/day; range, 1.3-9.2; n = 21) and CGHD (1.9 +/- 0.9 ng/day; range, 0.6-3.6; n = 14) groups from the NSC (12.8 +/- 3.1 ng/day; range, 9.3-17.5; n = 10) and NC (14.6 +/- 3.1 ng/day; range, 10.6-19.0; n = 6) groups without any overlap. A mean urinary hGH value less than 9.0 ng/day during a 2-day collection strongly suggested GH deficiency. Ten of 16 patients with PGHD and CGHD who received 2 IU met-hGH, sc, had urinary hGH levels within the range of the mean +/- SD in NSC. These patients received daily sc 0.097 +/- 0.024 IU/kg hGH injections. These results suggest that the measurement of 24-h urinary hGH excretion is noninvasive, accurate, and useful for the screening of GH deficiency. The mean value on 2 days of 24-h urinary hGH excretion for the screening of GH deficiency is estimated to be less than 9.0 ng/day. The optimal dose of GH as therapy for GH deficiency is demonstrated as daily sc injection of 0.1 IU/kg hGH, 0.7 IU/kg/week. To convert international units of met-hGH to milligrams, divide by 2.4. PMID- 2229308 TI - Changes in basal and stimulated growth hormone secretion in the aging rhesus monkey: a comparison of chair restraint and tether and vest sampling. AB - We studied basal serum GH and GH responses to iv clonidine and insulin-induced hypoglycemia in a group of four young (5-7 yr old) and four older (10-14 yr old) adult male rhesus monkeys under two restraint conditions, chair adaptation and a tether and vest system, to determine what changes in GH secretion occur with aging. The serum GH response to iv administration of GH-releasing hormone (GHRH) was also studied in the groups under tether and vest restraint. Serum samples were collected every 15 min and assayed for GH using a human GH RIA and for cortisol using an enzyme-linked immunosorbant assay. GH and cortisol concentrations in the young and older groups were analyzed with analysis of variance (ANOVA). In the chaired studies the older animals had a lower mean 6-h basal GH concentration than did the younger animals (2.7 +/- 0.8 vs. 3.5 +/- 0.5 micrograms/L; P = 0.0002). Prestimulation GH was lower before clonidine and insulin in the older chaired group (1.1 +/- 0.5 and 2.3 +/- 0.6 micrograms/L, respectively) compared to the younger group (3.6 +/- 0.8 and 3.8 +/- 0.7 micrograms/L, respectively; P less than 0.001). Poststimulation GH was lower after clonidine and insulin in the older chaired group (3.2 +/- 2.4 and 7.1 +/- 2.8 micrograms/L, respectively) compared to the younger chaired group (6.3 +/- 2.2 and 10.3 +/- 3.0 micrograms/L, respectively; P less than 0.05), but the differences in GH increments were not statistically significant. In the tether and vest studies the older animals had a lower mean 6-h basal GH concentration than did the younger animals (1.7 +/- 0.4 vs. 3.5 +/- 1.2 micrograms/L; P less than 0.0001). Prestimulation GH concentrations were also lower in the older tethered animals before clonidine (2.1 +/- 0.3 micrograms/L) and GHRH (1.4 +/- 0.2 micrograms/L) compared to levels in the younger animals (3.1 +/- 0.9 and 3.2 +/- 0.7 micrograms/L; P = 0.0023 and P = 0.0001, respectively). The younger tethered animals had greater poststimulation responses to clonidine (8.7 +/- 3.0 micrograms/L), insulin (8.8 +/- 3.6 micrograms/L), and GHRH (6.0 +/- 2.4 micrograms/L) than the older animals (3.8 +/- 0.9, 3.9 +/- 2.5, and 2.9 +/- 0.7 micrograms/L; P less than 0.0001, P = 0.0025, and P less than 0.03, respectively).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2229309 TI - Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects. AB - Although minimal model analysis of frequently sampled iv glucose tolerance tests (FSIGTs) to measure insulin sensitivity is well recognized, application has been limited by the need for endogenous insulin secretion. In the present study we determined whether use of exogenous insulin could permit minimal model assessment of insulin sensitivity (SI) to be extended to diabetic subjects. Normal volunteers had separate FSIGT assessments supplemented with both tolbutamide and insulin to accelerate glucose disappearance, while diabetics had a FSIGT supplemented only with insulin. There was a strong and highly significant correlation between the two assessments in normal subjects (r = 0.87; P less than 0.001), and the rank order of SI generally was maintained with the two assessments over a 3-fold range of SI; however, insulin-determined SI was 16% lower (3.4 +/- 0.4 vs. 4.1 +/- 0.4 x 10(-4) min/microU.microL; P less than 0.01). Diabetic subjects had markedly lower insulin sensitivity than controls (SI = 0.61 +/- 0.16; P less than 0.0001). Across all subjects, the level of fasting serum glucose was correlated inversely with both insulin sensitivity (r = -0.62; P less than 0.05) and acute insulin responses (r = -0.72; P less than 0.02); however, insulin sensitivity in diabetic subjects with little insulin secretion (0.6 +/- 0.2) was comparable to insulin sensitivity in diabetic subjects with near-normal responses (0.6 +/- 0.3). In subjects with fasting hyperglycemia, there were significant correlations between insulin sensitivity and body mass index, percent fat mass, and waist/hip ratio (all P less than 0.03). Among all female subjects, there was also a strong correlation between insulin sensitivity and upper body obesity, as measured by waist/hip ratio (r = -0.68; P less than 0.02). Model parameters also permitted glucose uptake to be estimated in diabetic vs. normal subjects at comparable hyperglycemia (11.1 mmol/L). Total glucose uptake was decreased in diabetic subjects (5.2 +/- 0.8 vs. 12.7 +/- 1.7 mg/min.kg in normals; P less than 0.001), insulin-dependent glucose uptake was diminished to a greater extent (1.3 +/- 0.4 vs. 6.2 +/- 1.2) than noninsulin-independent glucose uptake (3.9 +/- 0.5 vs. 6.4 +/- 0.9; both P less than 0.02). Administration of insulin permits minimal model FSIGT analysis to be applied to diabetic as well as normal subjects, yielding information about both insulin- and noninsulin-mediated glucose uptake as well as insulin sensitivity and insulin secretion. PMID- 2229310 TI - Pattern of oxytocin concentrations in the plasma and cerebrospinal fluid of lactating rhesus monkeys (Macaca mulatta): evidence for functionally independent oxytocinergic pathways in primates. AB - Two populations of oxytocin-staining neurons have been identified in the paraventricular nucleus: magnocellular neurons that terminate in the posterior pituitary and parvocellular neurons that terminate elsewhere in the central nervous system. Whether these oxytocin neurons are functionally separate was tested by measuring oxytocin concentrations in samples of peripheral blood and cerebrospinal fluid (CSF) obtained simultaneously from lactating rhesus monkeys during suckling. Lactating animals bearing temporary subarachnoid and venous catheters were maintained in a constant photoperiod (0600-1800 h). Samples of CSF were continuously withdrawn by peristaltic pump (0.1 mL/15 min) for 2-4 consecutive days from subarachnoid catheters with the tips placed at the T12-L1 level of the spinal column in four lactating monkeys 4 months postpartum and again after weaning. On 2 of these days, we observed and recorded periods of infant suckling and collected peripheral blood samples (1.2 mL) from the mother at 5-min intervals for 60 min. Oxytocin was measured in blood and CSF by RIA. Oxytocin concentrations increased in the plasma of the lactating monkeys during periods of nursing, with peak concentrations ranging from 4-16.7 microU/mL. No increase in plasma oxytocin was found on the day after the infant was weaned. Variations in the concentrations of oxytocin in CSF were independent of the suckling stimulus and plasma oxytocin concentrations and occurred during observed periods of no nipple contact by the infant and at the time of weaning after the infant had been removed from the mother. Each lactating animal also displayed a normal circadian variation in CSF oxytocin concentrations, with peak and nadir levels during light and dark hours, respectively. We conclude that release of oxytocin into the CSF of lactating monkeys is disassociated from release into the peripheral circulation. The data further support the conclusion that neuronal pathways giving rise to oxytocin in the CSF and the periphery are anatomically and functionally separate in primates. PMID- 2229311 TI - Nonosmotic stimuli alter osmoregulation in patients with spinal cord injury. AB - Studies on two quadriplegic patients who developed severe hyponatremia during episodes of acute respiratory distress were performed to determine whether differences in osmoregulation of vasopressin release could be identified in these patients compared to other quadriplegic subjects previously studied in a similar manner. Both patients were clinically stable and normonatremic, with no signs or symptoms of respiratory distress, when the studies were performed. However, both exhibited evidence of hemodynamic instability in the sitting posture. Linear regression analysis of the plasma vasopressin/plasma osmolality (Pavp:Posm) relationship during infusions of 0.85 M sodium chloride showed no significant differences in either the slope (sensitivity) or abscissal intercept (osmotic threshold) of this relationship compared to that of other quadriplegic subjects when the patients were supine. In contrast, when the patients were studied in the sitting posture there was a marked shift in the relationship of Pavp:Posm indicative of increased sensitivity and reduced osmotic threshold for vasopressin release. The slopes of the Pavp:Posm relationships were 0.249 and 0.178 for the two patients, respectively, compared to 0.092 +/- 0.03 ( +/- SD) for previously studied quadriplegic subjects. Oral water-loading studies performed on one patient revealed marked impairment of urine-diluting ability and free water clearance in the sitting posture compared with observations in similar studies performed when the patient was supine. Impairment of renal water excretion could not be attributed to an effect of vasopressin, which was reduced to unquantifiable levels by water loading. These studies have shown that hemodynamic stress related to autonomic dysfunction in quadriplegic patients may result in marked alteration of osmoregulation of vasopressin release in more severely affected individuals. Such altered osmoregulation, which may also be associated with vasopressin-independent impairment of renal water excretion in the sitting posture, may be a predisposing factor in the development of hyponatremia, especially in the presence of other potent nonosmotic stimuli. PMID- 2229312 TI - The circadian rhythm of intact parathyroid hormone-(1-84): temporal correlation with prolactin secretion in normal men. AB - Serum PTH-(1-84), PRL, and adjusted calcium concentrations were determined at 30 min intervals for a 24-h period in six normal adult men. PTH-(1-84) and PRL both exhibited two peaks of increased secretion [1600-1900 and 0200-0600 h for PTH-(1 84); 2000-2200 and 0400-0800 h for PRL]. For each subject there was a striking similarity in the magnitude of secretion of the two hormones and a consistent temporal relationship. Thus, the maximum correlation coefficients of 0.62-0.83 were obtained for the six subjects when the PRL surge lagged that of PTH-(1-84) by 0.5-3.5 h. In contrast, the correlation between PTH-(1-84) and adjusted calcium was weaker (r = -0.36 to -0.66) and showed no consistent temporal relationship (0.0-10.5 h). These data support the concept of higher center control of PTH-(1-84) secretion with the possible involvement of factors common to the control of PRL secretion. PMID- 2229313 TI - Parathyroid hormone and cirrhosis of the liver. AB - Fifty patients with liver cirrhosis (36 alcoholic, 1 drug-induced, 7 posthepatitic, and 6 cryptogenic) and normal renal function were investigated to determine whether PTH levels in serum, measured using the common midregion human PTH-(44-68) RIA, are elevated in such patients and whether this is related to impaired liver function rather than to the effect of secondary hyperparathyroidism. Their data were compared with those from 25 control subjects. The median PTH level of 462 +/- 18 ng/L (+/- SEM) was significantly increased (P less than 0.01) in cirrhotics compared with that of 236 +/- 13 ng/L in the control group. Significant correlations were found between PTH levels and parameters of liver function such as prothrombin time (r = -0.40; P less than 0.01), albumin as a percentage of total protein (r = -0.48; P less than 0.01), bilirubin (r = 0.35; P less than 0.05), albumin (r = -0.34; p less than 0.05), and cholesterol (r = -0.32; P less than 0.05), but not for antipyrine clearance, suggesting increasing PTH with decreasing liver function. The median calcium level (2.26 +/- 0.03 mmol/L), corrected for changes in albumin, was near the lower limit of the normal range (2.25-2.60), but corrected calcium and PTH were positively correlated (r = 0.33; P less than 0.05), indicating that the elevation is not reactive to calcium depletion. A negative correlation existed between PTH and 25-hydroxy-cholecalciferol (r = -0.49; P less than 0.05), the main circulating metabolite of vitamin D. Normal values in an immunoradiometric assay that detects the whole sequence of human PTH-(1-84) suggest that fragments rather than the intact hormone are responsible for PTH elevations in cirrhosis. The positive correlation between midregion PTH and corrected calcium is probably an artifact of the correction formula. In conclusion, midregion PTH fragments are increased in patients with liver cirrhosis. The reason for this elevation may well be the impaired liver function rather than secondary hyperparathyroidism. PMID- 2229314 TI - Tumor necrosis factor: a putative mediator of the sick euthyroid syndrome in man. AB - Tumor necrosis factor-alpha (TNF) is believed to be an important mediator in many diseases that are associated with the sick euthyroid syndrome. To investigate the effect of TNF on thyroid hormone metabolism, we performed a controlled study in six healthy postabsorptive males, in whom plasma thyroid hormones and TSH were sequentially measured after iv bolus injections of recombinant human TNF (50 micrograms/m2) and isotonic saline. During the 10.5-h study TNF produced the characteristic changes in circulating thyroid hormones and TSH observed in the sick euthyroid syndrome. Compared with the control experiment, TNF induced significant decreases in T3 (-36 +/- 2%; saline, -20 +/- 3%; P less than 0.05) and TSH levels (-68 +/- 3%; saline, -44 +/- 8%; P less than 0.05) and a significant increase in rT3 values (+48 +/- 11%; saline, -12 +/- 7%; P less than 0.05). T4 and free T4 index were not affected by TNF. Free T4 showed a mean transient increase of 18% in five subjects (nonsignificant), which occurred synchronically with a transient 3.5-fold rise in circulating FFA levels. Our results suggest that TNF is involved, either directly or indirectly, in the pathogenesis of the sick euthyroid syndrome. PMID- 2229315 TI - Transport of thyroid hormones by human erythrocytes: kinetic characterization in adults and newborns. AB - The uptake of [125I]T3 and [125I]T4 by human erythrocytes was studied. The erythrocytes were obtained from adult subjects (28-41 yr old) and suspended in a protein-free medium. The half-times of equilibration for both T3 and T4 were 6 min. At equilibrium, T3 was concentrated 55-fold inside the cells, while T4 was concentrated 40 times, but these accumulations were not dependent on either cellular ATP or the transmembrane Na+ gradient. The amounts of cell-associated thyroid hormones were 20 times (T3) and 17 times (T4) higher than the amounts of free extracellular hormones at 5 X 10(9) erythrocytes/mL (the blood concentration). Oligomycin and phloretin inhibited T3-saturable transport (but not T4 transport) independently of cellular energy. We suggest that thyroid hormones are concentrated by intracellular trapping. The rates of T3 and T4 efflux from preloaded erythrocytes were similar to the influx rates. The initial velocities of T3 (but not T4) uptake and efflux were 70% saturable. The uptake was specific because the unlabeled analogs T4, triiodothyroacetic acid, rT3, D T3, and D,L-thyronine inhibited [125I]T3 uptake 60, 125, 160, 190, and 1600 times less, respectively, than did unlabeled T3. The kinetic parameters of T3-saturable uptake, Km, and maximum velocity were determined for three groups of subjects: newborns, 28 to 41-yr-old adults, and 76 to 90-yr-old adults. The Km (67 nmol/L in 28 to 41-yr-old adults) was not age dependent, BUT the maximum velocity was significantly higher in newborns than in adults. We conclude that T3 transport across the human erythrocyte membrane is mediated mainly by facilitated diffusion, whereas T4 transport results from free diffusion. Human erythrocytes might act as a circulating pool of thyroid hormones, especially T3 in newborns. PMID- 2229316 TI - Thyroid abnormalities in the McCune-Albright syndrome: ultrasonography and hormonal studies. AB - Hyperthyroidism and goiter have been reported frequently in association with the McCune-Albright syndrome (MAS). To assess the prevalence and extent of thyroid abnormalities in girls with MAS, we studied 19 patients [mean age, 6.6 +/- 1 (+/- SE) yr; mean bone age, 9.5 +/- 1 yr] and 18 normal control girls (mean age, 10.3 +/- 0.5 yr). All patients appeared euthyroid when examined; 1 was taking antithyroid medication. Ultrasonography revealed thyroid abnormalities in 7 patients, including generalized inhomogeneity, small (2-4 mm) and large (greater than 10 mm) hypoechoic regions, and echogenic nodule-like regions. Repeat ultrasonography after intervals of 9-18 months showed enlargement of large hypoechoic regions in 2 patients. In the patients with abnormal ultrasound findings, serum TSH was uniformly low or suppressed both at baseline and after administration of 7 micrograms/kg TRH. The mean serum T3 level in this group was significantly higher than that in controls (2.9 +/- 0.2 vs. 2.3 +/- 0.1 nmol/L; P less than 0.05), whereas mean serum T4, free T4, and T4-binding globulin levels did not differ from those of controls. In the remaining 11 patients, thyroid ultrasonography was normal, and the serum levels of T3, T4, free T4, and TSH were normal. Bioassay showed no detectable thyroid-stimulating activity in the plasma of the MAS patients with suppressed TSH levels. None of the patients became overtly thyrotoxic over 3-6 yr of observation, and their serum iodothyronine levels remained stable. We conclude that thyroid dysfunction is common in girls with MAS, but that it may be clinically occult and not rapidly progressive. The thyroid dysfunction, like that of the ovaries, is associated with structural abnormalities in the gland itself, together with suppressed levels of the respective stimulating hormones. PMID- 2229317 TI - Brain glucose metabolism in noninsulin-dependent diabetes mellitus: a study in Pima Indians using positron emission tomography during hyperinsulinemia with euglycemic glucose clamp. AB - To determine whether insulin or noninsulin-dependent diabetes mellitus affects brain glucose metabolism, brain glucose utilization was studied in the basal state and during hyperinsulinemic euglycemic glucose clamps in nondiabetic and diabetic Pima Indians by positron emission tomography with 2-[18F]fluoro-2-deoxy D-glucose (18FDG). Glucose utilization in 75 brain areas was determined by analysis of single scans and by least squares estimation of the rate parameters for the FDG model; these data were compared to results in normal caucasian volunteers. No effect of ethnicity or diabetic status on brain glucose utilization was observed. During the hyperinsulinemic clamps (mean insulin, 11,708 +/- 3,026 pmol/L), clearance of 18FDG from blood was accelerated, and accumulation of brain radioactivity was reduced. However, glucose utilization by the brain was identical to results during sham glucose clamps (mean insulin, 204 +/- 56 pmol/L) performed in the same patients. During the studies with hyperinsulinemia, k4 (representing loss of tissue radioactivity) was increased in most brain areas (mean increase, 0.0031 +/- 0.0018 min-1; P less than 0.02). The possible mechanisms for this effect are multiple, and the physiological significance, if any, is unknown. Further studies of the effects of insulin on brain glucose metabolism are needed. PMID- 2229318 TI - Endothelin family in human plasma and cerebrospinal fluid. AB - To clarify whether endothelin may be present in human cerebrospinal fluid (CSF) and, if it exists, to compare its molecular forms with those of endothelin in human plasma, we analyzed pooled human CSF and plasma by high performance liquid chromatography with specific enzyme immunoassays for each endothelin peptide. Of the four human endothelin peptides hitherto identified, big endothelin-1 was the major molecular form of endothelin present in human CSF. In addition, there was a small but significant amount of endothelin-1 and endothelin-3 in CSF, while endothelin-2 was not detectable. Similarly, big endothelin-1, endothelin-1, and endothelin-3 were identified in human plasma. Although big endothelin-1 was the most abundant, a substantial amount of endothelin-1 and endothelin-3 was found in plasma with a resultant lower molar ratio of big endothelin-1 to endothelin-1 than in CSF. In all CSF samples from 17 patients requiring diagnostic lumbar puncture or lumbar anesthesia, endothelin was detectable, with a preponderance of big endothelin-1 relative to endothelin-1 and endothelin-3. The mean concentrations of endothelin-1 and endothelin-3 in simultaneously collected plasma were significantly (P less than 0.01) higher than those in CSF, while there was no significant difference between the mean big endothelin-1 concentration in plasma and that in CSF. There was no significant correlation among concentrations of big endothelin-1, endothelin-1, and endothelin-3 in each paired sample. These results indicate that endothelin is present in human CSF that is differently processed from endothelin in vascular endothelial cells and suggest a possible role for endothelin as a modulator of neuronal functions. PMID- 2229319 TI - Human oxysterol-binding protein. I. Identification and characterization in liver. AB - The function of cellular oxysterol-binding proteins is not known. Because of the proposed receptor-like role of these proteins in regulating cholesterol synthesis and the importance of the liver in the cholesterol metabolism of the body, we have studied the oxysterol-binding sites found in specimens of human liver. A protein that binds with high affinity to certain oxygenated derivatives of cholesterol has been identified and characterized in several ways. When 25 hydroxy-[3H]cholesterol is used as ligand, specific binding components can be identified in cytosolic liver extracts fractionated on sucrose density gradients in the fractions sedimenting at 4S and 7S. Cholesterol and steroid hormones do not compete for these binding components, but several oxysterols do. In cytosolic extracts, all binding appears to be a single class kinetically, with an apparent Kd of 28 x 10(-9) mol/L. We found the protein responsible to have a pI of about 4.8. Purification of the protein allowed preparation of an antiserum and subsequent immunoprecipitation of a photoaffinity-labeled component from crude cytosolic extracts. Electrophoresis of the immunoprecipitates revealed a single specifically labeled protein band, with a mol wt of about 57,000. The protein described here may have a regulatory role in the synthesis of cholesterol in the human. PMID- 2229320 TI - Reliability of estimates of pulsatile characteristics of luteinizing hormone and growth hormone release in women. AB - The test-retest reliability of estimates of pulsatile LH and GH release was evaluated in 23 eumenorrheic women during the early follicular phase of the menstrual cycle. Each subject was studied during two successive or near successive menstrual cycles by repetitive blood sampling every 10 min for 24 h. Pulsatile parameters for LH and GH release were identified and characterized using the Cluster pulse detection algorithm. For LH, no significant differences existed in any parameter mean between the two 24-h admissions. Correlation coefficients for consecutive 24-h studies ranged from r = 0.22 (P less than 0.32) for number of LH peaks to r = 0.79 (P less than 0.0001) for 24-h integrated LH values (area under the concentration vs. time curve). No significant mean differences in any parameter were observed for consecutive 24-h GH evaluations. Correlation coefficients for 24-h GH ranged from r = 0.25 (P less than 0.34) for nadir to r = 0.71 (P less than 0.002) for incremental peak increase. Cosinor analysis was used to determine significant 24-h variations in LH and GH concentrations. Statistically significant differences existed between admissions for the amplitude of the nyctohemeral LH rhythm and its acrophase (time at which maximal hormone value was attained), but no mean differences were found for mesor (mean concentration). Correlation coefficients for LH were r = 0.10 (P less than 0.65), r = 0.43 (P less than 0.08), and r = 0.78 (P less than 0.0001) for phase, amplitude, and mesor, respectively. No significant mean differences existed for any parameter of nyctohemeral GH rhythms. Correlation coefficients were r = -0.18 (P less than 0.52), r = 0.49 (P less than 0.72), and r = 0.14 (P less than 0.80) for 24-h GH amplitude, phase, and mesor, respectively. We conclude that comparisons of mean and integrated LH and GH concentrations over a 24-h interval in the early follicular phase of the menstrual cycle are reliable; however, certain pulsatile properties responsible for the achievement of the mean daily concentrations of LH and GH may be nonuniform from menstrual cycle to menstrual cycle. In addition, nonuniformities may exist in the nyctohemeral rhythms of serum concentrations of LH and GH in the adult woman between cycles when a single 24-h time series is the basis for the analysis. PMID- 2229321 TI - Gastrointestinal side-effects of octreotide during long-term treatment of acromegaly. AB - Gastrointestinal side-effects of prolonged therapy (greater than 2 yr) with the long-acting somatostatin analog octreotide were studied in 10 acromegalic patients. After 2 yr of therapy, 6 of 10 patients had newly developed gallstones, complicated by cholangitis and jaundice in 1. Serum vitamin B-12 concentrations declined in all 10 patients [from 380 +/- 32 to 172 +/- 21 pmol/L (mean +/- SE); P = 0.023] and became abnormally low in 4. Gastric biopsy specimens, obtained during gastroscopy (9 patients), showed moderate to severe active gastritis, with damage to the superficial and deeper layers of the mucosa in 9 of 9 and focal atrophy in 7 of 9 patients. Campylobacter pylori was found in the antral mucosa in 8 of 9 patients. Although information is lacking on similar studies in untreated acromegalic patients, we suggest that patients receiving chronic octreotide therapy be closely monitored for these and possible other side-effects related to gastrointestinal actions of octreotide. PMID- 2229322 TI - Thyroiditis as the presenting manifestation of disseminated extrapulmonary Pneumocystis carinii infection. AB - A 38-yr-old male with acquired immunodeficiency syndrome developed neck pain in association with mild hyperthyroidism and a diffusely enlarged thyroid gland. Radioactive iodine scanning was consistent with thyroiditis, and biopsy of the thyroid demonstrated the presence of pneumocystis carinii in thyroid tissue. Treatment with pentamidine followed by trimethoprim sulfamethoxazole led to rapid normalization of thyroid size in association with the development of hypothyroidism. This case illustrates the natural history of pneumocystis carinii thyroiditis and suggests that thyroid disease be added to the spectrum of human immunodeficiency virus-associated endocrine dysfunction. PMID- 2229323 TI - Anti-5 alpha-reductase autoantibodies in the serum of patients with prostatic cancer. AB - Human sera were tested for their ability to inhibit 5 alpha-reductase binding of a potent inhibitor of the enzyme. Thirty one of 227 serum samples from patients diagnosed or suspected of prostatic cancer had a significant inhibitory activity, whereas 128 serum samples from other patients were inactive. The majority of the inhibitory activity was in the IgG fraction purified by chromatography on a protein A-Sepharose affinity column and an anti-human IgG-agarose column. IgG fractions from non-inhibitory sera were inactive. Inhibitory IgG also inhibited the enzymatic activity of microsomal 5 alpha-reductase from liver, ventral prostate and preputial gland of rat, and liver, prostate, and facial skin of human. The inhibitory IgG had no effect on NADH-menadione reductase or 17 beta hydroxysteroid dehydrogenase. These results suggest that 5 alpha-reductase autoantibodies are present in the blood of some prostatic cancer patients. PMID- 2229324 TI - Women with preeclampsia have higher plasma endothelin levels than women with normal pregnancies. AB - Endothelin, a newly discovered endothelium-derived peptide, has potent vasoactive properties in vivo and in vitro. The actions of endothelin in clinical conditions of hypertension have not yet been defined. This study examined the possible role of endothelin in the vasospasm and hypertension associated with a well-defined syndrome of gestational hypertension, preeclampsia. Our results indicate that the concentration of immunoreactive endothelin is elevated significantly in plasma obtained from women with preeclampsia and rapidly returns to a normal pregnancy value within 48 hours of delivery, as predicted by the prompt clinical resolution of this disorder. The findings suggest that endothelin may contribute to the vasospasm associated with this syndrome and lend further support to the involvement of endothelial cells in the pathophysiology of preeclampsia. PMID- 2229325 TI - Human recombinant activin-A inhibits proliferation of human fetal adrenal cells in vitro. AB - Activins and inhibins are dimeric peptides which are structurally and functionally related to transforming growth factor-beta (TGF-beta). The mRNA for the activin and inhibin subunits is expressed in the adrenal gland. Because members of the TGF-beta superfamily have effects on mitogenesis, we examined the effect of recombinant human activin-A (rh-activin-A) on proliferation of midgestation human fetal adrenal cells in vitro. Dose-dependent growth inhibition by rh-activin-A was obtained, with an ED50 of 1 ng/ml. Rh-activin-A inhibited basal and epidermal growth factor (EGF)-stimulated fetal zone cell proliferation, but did not alter basic fibroblast growth factor (bFGF)-stimulated growth. TGF beta combined with rh-activin-A demonstrated additive inhibition of fetal adrenal growth. These findings suggest a potential autocrine or paracrine role for activin-A in modulating the growth and/or subsequent involution of the human fetal adrenal gland. PMID- 2229326 TI - Endothelin-like immunoreactivity in human breast cyst fluid. AB - Immunoreactive endothelin has been detected in 21 of 43 samples of breast cyst fluid (21 cases; 3.5 +/- 0.6 pmol/l, mean +/- SEM. Other 22 cases; not detectable, less than 0.5 pmol/l). Fast protein liquid chromatographic analysis of the immunoreactive endothelin of pooled breast cyst fluid showed two immunoreactive peaks; one in the void volume and the other in the position of endothelin-1. It is probable that endothelin-1 is produced by the epithelial cells lining breast cysts, but significance of the presence of endothelin-1 in breast cyst fluid remains to be elucidated. PMID- 2229327 TI - Electrical activities of pyramidal cells in the kindled hippocampus of the rabbit. AB - 1) The pyramidal cell in the kindled hippocampus of the rabbit was intracellularly studied and compared with that in the normal hippocampus. 2) As previously reported, what characterized the kindled hippocampus was the appearance of a spontaneous hyperpolarization in the pyramidal cell. Practically all the pyramidal cells in the kindled hippocampus showed spontaneous hyperpolarizations. The hyperpolarization consisted of Cl-dependent and Cl-non dependent components. The former was evidently the somatic IPSP. On the other hand, the latter was interpreted as the dendritic IPSP. This was supported by the fact that there was an interictal positivity in the apical dendrite layer. 3) There was no evidence whatsoever that indicated an increased excitability of the pyramidal cell. This showed that the kindled hippocampus was essentially different from the penicillin-treated hippocampus. It was suggested that the former was similar to the human brain in the interictal phase, whereas the latter was similar to that in status epilepticus. 4) In a few pyramidal cells there was a slow depolarization which could possibly trigger a seizure discharge and the nature of the slow depolarization was discussed. However, the slow depolarization was not peculiar to the kindled hippocampus. PMID- 2229328 TI - [The blood urea nitrogen/creatinine ratio in localizing the bleeding site in pediatric patients with gastrointestinal hemorrhage]. AB - The reliability of the blood urea nitrogen/creatinine (B/C) ratio in localizing the bleeding site in pediatric patients with gastrointestinal hemorrhages was evaluated retrospectively. Supplementary experiments on rats and rabbits were also conducted. The study population included 69 children ranging in age from 6 days to 16 years (mean age, 7y8m) with successful radiographic, endoscopic, and surgical identification of the bleeding site. Patients with renal disease, liver disease and coagulopathy were excluded. The upper gastrointestinal bleeding site was segregated from the lower one defined by the ligament of Treitz. For the 38 upper gastrointestinal bleeders, B/C values ranged from 7.8-69.0 (mean 28.8 +/- 15.4 SD). For the 31 lower gastrointestinal bleeders the values ranged from 4.3 28.5 (mean 18.9 +/- 6.9 SD). A significant difference between the two groups was noted after (p less than 0.01) analysis. No patients with lower gastrointestinal bleeding had values higher than 30. In the group of 17 bleeders with a value higher than 30, 8 patients were examined again from 2-5 days after they had been identified as having bleeding to prove that the bleeding had stopped. At the time of identification of no-bleeding, B/C values were calculated at under 30 in every patient. There was no significant correlation between Hb (g/dl) and B/C. With respect to our experiments on animals, the B/C ratio was evaluated in rats with gastric or small intestinal ulcers. Though B/C was 34.4 +/- 4.4 under normal conditions, it increased significantly to 114.0 +/- 8.8 in rats with gastrointestinal ulcers, while in those with small intestinal ulcers B/C did not increase significantly (40.3 +/- 12.3). Twenty ml of blood from ear veins of rabbits was infused into a) stomach b) small intestine (no-hemolysis blood) c) small intestine (hemolysis blood). For a) and c), B/C increased in a similar pattern. For b) the increase was small. Infusing 5 ml, 10 ml, and 15 ml of the whole blood into the stomach indicated that the volume of blood did not influence the change of B/C values, while the infusion of 3 ml of serum caused only a small increase. According to these studies the increase in the B/C ratio after upper gastrointestinal hemorrhage has been postulated to result from the procedure in which the hemorrhage blood is fragmented or hemolyzed by HCl and digestive enzymes in the gastric juices; and consequently the BUN in red blood cells as well as in serum is rapidly absorbed from the upper small intestine. Volume of blood has little influence upon B/C.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2229329 TI - Early increase in K+ conductance during metabolic inhibition by cyanide in guinea pig ventricular myocytes. AB - The underlying mechanism of the early increase in K+ conductance during metabolic inhibition was examined by the whole-cell patch clamp technique. To inhibit oxidative phosphorylation, cyanide (0.1-1.0 mM) was superfused to enzymatically isolated guinea pig ventricular myocytes. The increase in the outward K+ current during the metabolic inhibition consisted of at least two components; one was a gradual and small increase which appeared within 5 min, and the other was a subsequent sudden and large increase occurring 17.8 min on average after cyanide application at a concentration of 0.1 mM. The earlier component of the cyanide sensitive current was examined by the square pulse method. The current had a reversal potential of -76.0 mV and an inward-rectifying property. When cyanide (0.1 mM) was applied for 10-12 min, the chord conductance of the inward rectifier K+ current (IK1) was significantly increased and its voltage relation was shifted to hyperpolarizing direction (-2.3 mV). The cyanide could not induce an outward current in K(+)-free ionic condition or in the presence of extracellular Ba2+ (2 mM), a blocker of the IK1. However, the outward current even appeared in the presence of 5 mM ATP in the perfused solution in pipette, while it attenuated when intracellular pH was buffered with 50 mM HEPES in the pipette solution. These observations suggest that the early increase in K+ conductance during the metabolic inhibition is due to the augmented IK1 conductance and not due to the induction of ATP-sensitive K+ current. The increase in the K+ conductance may be caused by the intracellular pH change, probably through intracellular metabolic acidosis by the inhibited oxidative phosphorylation. PMID- 2229330 TI - [A study of granular lymphocytes (GL) in children and young adults]. AB - In this study, we investigate the percentage and absolute number of granular lymphocytes (GL) in venous blood smears and the percentage of CD16+ and CD57+ lymphocytes in the peripheral venous blood of 91 healthy controls (1 to 29 years old) and 168 patients with various diseases (1 month to 36 years old). GL were morphologically classified into four subsets: large-sized lymphocytes with large granules (LL-LG), large-sized lymphocytes with small granules (LL-SG), medium sized lymphocytes with large granules (ML-LG) and medium-sized lymphocytes with small granules (ML-SG). The results were as follows: 1) In the controls, the percentage of GL in total lymphocytes was 10.0 +/- 6.2% (mean +/- 1SD). Therefore its normal value was below 22.4% (mean +/- 2SD). The absolute count of GL was 320.7 +/- 221.0/mm3. The percentages of LL-LG, LL-SG, ML-LG and ML-SG in total lymphocytes were 1.7 +/- 2.2%, 2.3 +/- 2.8%, 2.6 +/- 2.3% and 3.4 +/- 2.7%, respectively. 2) In flow cytometric studies, the percentage of CD16+ in the controls was 10.2 +/- 6.7%; CD57+, 8.2 +/- 5.1%; CD57+ CD16+, 4.2 +/- 3.3%; CD57+ CD16-, 4.0 +/- 2.8%; CD57- CD16+, 6.4 +/- 4.8%. The distribution patterns of lymphocytes by two-color analysis with FITC-labelled anti-CD16 and PE-labelled anti-CD57 monoclonal antibodies in the controls were classified into four groups. 3) Only seven of the 168 patients exhibited significantly high percentage of GL in total lymphocytes. They consisted of 4 splenectomized patients and 3 patients with pancytopenia, two of whom had pancytopenia complicated by immunoglobulin deficiency. Five of the 7 patients also had markedly high percentage of CD16+ and/or CD57+ lymphocytes. In these 5 patients, the ratios of four subsets of GL and the distribution patterns of lymphocytes with CD16 and CD57 surface antigens were different from the patient to patient and those for controls. PMID- 2229331 TI - [Clinical aspects and intracranial pressure monitoring in cases of traumatic posterior fossa hematoma]. AB - Clinical signs, skull X-P, computerized tomography (CT), continuous monitoring of intracranial pressure (ICP), and serial recording of auditory brainstem response (ABR) were examined in 22 cases of traumatic posterior fossa hematoma. Fifteen of the patients were male and seven were female. Their ages ranged from 3 to 86 years old (mean 35.2 years). The causes of the head injuries were traffic accidents in 13 cases and falls in 9 cases. The site of cranial impact was occipital in all cases but one. Sagittal impact was most common and skull fractures were found in the occipital regions in 19 cases. States of consciousness on admission as measured by the Glasgow coma scale (GCS) were GCS 15 in 2 cases, GCS 9-14 in 9 cases and GCS 3-8 in 11 cases. CT findings of posterior fossa included 10 cases of intracerebellar hematoma, 8 cases of epidural hematoma, 2 cases of combined epidural and intracerebellar hematoma and 2 cases of subdural hematoma. Associated CT findings of the supratentorial region were noted in 18 cases (82%), and most of them showed contrecoup injuries in the frontal region. Six cases of 8 epidural hematomas of the posterior fossa indicated combined epidural hematomas in the occipital region. ICP was monitored in 11 of the 22 cases. Pre-operative ICP monitoring (5 cases) indicated an operative decision. ABR was recorded in 5 cases. Serial ABR recording provides reliable information about brain stem function. The hematoma was evacuated in 15 cases. The Glasgow outcome scale administered 3 months after trauma indicated good recovery in 2 cases, moderate disability in 6 cases, severe disability in 2 cases, persistent vegetative state in 1 case and death in 9 cases. It has become obvious that there are many types of CT findings in posterior fossa hematomas, and that continuous ICP monitoring is very important to determine the timing of surgery and to protect against secondary brain damage caused by increased ICP. PMID- 2229332 TI - [Clinical and histopathological observations of pigmented spots on the feet]. AB - Malignant melanomas, originating in the foot are said to have a higher frequency in Japan compared to Western countries, accounting for almost one third of all cutaneous malignant melanomas. In this context, pigmented spots on the feet which can be thought of as precursor lesions of malignant melanomas attract a great deal of attention from clinical dermatologists. In this study, 159 pigmented spots, consisting of 110 on the soles as well as 49 on the dorsal lesion have been studied clinically and histopathologically to clarify their relationship with the development of malignant melanomas. The results were as follows: 1) Junction nevi were most commonly observed at both sites. 2) Lesions tended to be darker in color and bigger in size as they proceeded from the simple lentigo to the junctional and compound nevi. 3) Most of the lesions were flat, but the elevated lesions were seen more frequently in the compound nevi and intradermal nevi which contained more dermal components. Also, lesions on the soles appeared to be more elevated. 4) Among the 21 cases which showed some cutaneous change, one case showed histopathological evidence of a premalignant lesion. 5) In the pigmented spots on the feet, the initial signs of premalignant transformation were skin elevation, more pronounced spot growth, measuring up to 5 mm in diameter, and dark black coloring (pigmentation). Therefore preventive excision of the lesion is recommended in cases where any of the three above features are in evidence. PMID- 2229333 TI - [Imaging diagnosis of breast disease]. PMID- 2229334 TI - [Surgical treatment of breast cancer, today]. PMID- 2229335 TI - [Autoradiographic method for measuring regional cerebral blood flow in rat]. PMID- 2229336 TI - Abstracts of the second joint meeting of the European Society of Human Reproduction and Embryology and the European Sterility Organization. PMID- 2229337 TI - Mechanism of plasma clotting by Erysipelothrix rhusiopathiae. AB - Experiments were performed to determine the mechanism by which Erysipelothrix rhusiopathiae clots plasma. Detection of plasma-clotting activity in four strains of E. rhusiopathiae was carried out by mixing a 24-h broth culture of a tested bacterial strain with rabbit plasma (tube coagulation test). Sodium citrate, sodium oxalate, EDTA, and heparin were used as anticoagulants in preparing the rabbit plasma. E. rhusiopathiae strains clotted solely citrated plasma in 18 to 24 h. A known coagulase-positive strain of Staphylococcus aureus clotted all of the plasma preparations within 1 h. Various constituents of the organisms, such as cell-free culture filtrates, sonicated extracts, and Formalin-killed bacteria, were also checked for their ability to clot citrated plasma. No constituents of any strain of E. rhusiopathiae clotted the plasma. Only culture filtrates of S. aureus clotted the plasma under these conditions. The spectrophotometric assay demonstrated that two plasma-clotting strains of E. rhusiopathiae consumed the citrate in the plasma just before clotting. Of 301 veterinary clinical isolates of E. rhusiopathiae, 267 (88.7%) were positive in the tube coagulation test. On the basis of these results, it was concluded that plasma clotting by E. rhusiopathiae was due not to extracellular factors such as staphylocoagulase but to consumption of the citrate in the plasma. PMID- 2229338 TI - Rapid biochemical test to identify verocytotoxin-positive strains of Escherichia coli serotype O157. AB - Fluorogenic procedures were used with the substrate 4-methylumbelliferyl-beta-D glucuronide (MUG) to identify Escherichia coli. Most strains produced beta glucuronidase and, thus, were MUG positive. A 20-min procedure was developed to detect glucuronidase activity in 1,295 bacterial cultures, representing 23 genera, of strains that were isolated from clinical specimens. Very few organisms other than E. coli were MUG positive. Of 682 E. coli strains that were isolated, 630 (92.4%) were MUG positive. When an additional 188 E. coli serotype O157 isolates were examined, 155 E. coli O157:H7, 10 E. coli O157:H-, and 1 E. coli O157:H (rough) isolate were MUG negative. All 166 cultures were verocytotoxin positive. Of the remaining 22 E. coli O157 isolates, 2 isolates were O157:H-, 1 isolate was O157:H (rough), and 19 isolates were other H types (H6, H16, H19, H25, H42, and H45); these 22 isolates were MUG positive. All 22 cultures were verocytotoxin negative. The rapid MUG procedure can be used to predict verocytotoxin-positive isolates of E. coli O157; that is, there is a very good likelihood that MUG-negative E. coli O157 isolates are verocytotoxin positive. PMID- 2229339 TI - Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting analysis of smooth-lipopolysaccharide heterogeneity among Brucella biovars related to A and M specificities. AB - Smooth (S)-lipopolysaccharide (LPS) preparations from reference and field strains of several biovars of Brucella abortus, B. melitensis, and B. suis were prepared by (i) the hot phenol-water method, (ii) hot sodium dodecyl sulfate extraction and proteinase K digestion, or (iii) dimethyl sulfoxide extraction. These S-LPS enriched fractions were further analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining after periodate oxidation. Immunoblots were developed by using either monoclonal antibodies specific for Brucella A or M antigens or polyclonal polyspecific or monospecific sera from rabbits, cattle, and goats. The specificity of monoclonal antibodies reactive with Brucella unique (A or M) epitopes was demonstrated by enzyme-linked immunosorbent assay, LPS latex agglutination, or agglutination inhibition. The most-represented subunits of S-LPS ranged in Mr from 30,000 to 70,000 relative to marker proteins. According to A or M immunodominance, two sodium dodecyl sulfate-polyacrylamide gel electrophoresis banding patterns were clearly distinguished among biovars, whatever the fraction tested: a close succession of regularly spaced narrow bands for A greater than M strains and regularly spaced triplets of bands including either (i) a first thin band followed by two thick bands for B. abortus M greater than A strains or (ii) one thick band between two thin bands for B. melitensis or B. suis M greater than A strains. Moreover, A and M specificities were reaffirmed by sandwich enzyme immunoassay and latex agglutination inhibition with monoclonal antibodies and polyclonal sera. PMID- 2229340 TI - Recombinant fusion protein for simple detection of Escherichia coli heat-stable enterotoxin by GM1 enzyme-linked immunosorbent assay. AB - A recombinant gene fusion protein composed of an Escherichia coli heat-stable enterotoxin (STa) peptide epitope fused to the amino end of the cholera toxin B subunit was used to detect STa produced by clinical isolates of enterotoxigenic E. coli (STa-ETEC) by a single monoclonal antibody-based inhibition GM1 enzyme linked immunosorbent assay. In this test, 100% sensitivity and 100% specificity were observed for use of the recombinant protein in either its purified form or as crude Vibrio cholerae culture supernatants in detection of STa-ETEC. PMID- 2229342 TI - Detection and quantitation by lysis-filtration of bacteremia after different oral surgical procedures. AB - Patients with bacteremia after dental extraction, third-molar surgery, dental scaling, endodontic treatment, and bilateral tonsillectomy were studied by means of lysis-filtration of blood samples with subsequent aerobic and anaerobic incubation. Samples were obtained before, during, and 10 min after treatment. Bacteremia was observed in 100% of patients after dental extraction, 55% of patients after third-molar surgery, 70% of patients after dental scaling, 20% of patients after endodontic treatment, and 55% of patients after bilateral tonsillectomy. Anaerobic microorganisms were isolated more frequently than aerobic microorganisms were, and viridans group streptococci were the most commonly isolated bacteria. Ten minutes after treatment, the frequency as well as the magnitude of bacteremia showed pronounced reduction. PMID- 2229341 TI - Monoclonal antibody recognizing a species-specific protein from Streptococcus pneumoniae. AB - Monoclonal antibodies (MAbs) against a nonencapsulated strain (R36A) of Streptococcus pneumoniae were produced to aid in a search for antigens common to this species. By Western immunoblot analysis, a species-specific 37-kilodalton (kDa) protein was found in lysates of 24 different encapsulated strains of S. pneumoniae. Monoclonal antibodies against the 37-kDa antigen did not react with 55 heterologous strains representing 19 genera and 36 species of bacteria that can also cause acute lower respiratory tract disease. Immunogold staining suggests that the antigen is synthesized inside the pneumococcal cell. However, MAbs to the 37-kDa antigen bound whole cells in the enzyme-linked immunosorbent assay and the indirect immunofluorescence assay. Antibody-binding epitopes of the antigen are probably exposed on the outer surface of the pneumococcus cell wall. The effectiveness of the 37-kDa antigen as a useful diagnostic marker is under study. PMID- 2229343 TI - Characterization of flagella of Clostridium difficile and their role in serogrouping reactions. AB - Slide agglutination with rabbit antisera allows the differentiation of 10 serogroups of Clostridium difficile, namely, A, B, C, D, F, G, H, I, K, and X. Each serogroup displays a specific protein profile in sodium dodecyl sulfate polyacrylamide gel electrophoresis, except for A, which displays 12 different protein profiles (A1 to A12). In the present work, electron microscopy revealed the presence of uniformly distributed flagella in the reference strains of serogroups G and K and in all strains representative of the 12 subgroups within serogroup purified by differential centrifugation. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of these preparations revealed one distinct band with an apparent molecular mass of approximately 39 kilodaltons. Antiserum was prepared by immunizing a rabbit with the serogroup A flagellin, which had been eluted from the gel. In immunoblotting, this antiserum cross-reacted with the flagellin of the other strains. When the cells were deflagellated by a short sonication, the cross-reactions observed by slide agglutination with A, G, and K antisera were suppressed. Similarly, shearing of flagella allowed specific slide agglutination of the 12 subgroups of serogroup A. PMID- 2229344 TI - Beta 2-microglobulin and neopterin: predictive markers for human immunodeficiency virus type 1 infection in children? AB - The value of beta 2-microglobulin and neopterin concentrations in serum for early diagnosis of infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers was assessed. Concentrations of both markers were measured in serum samples from pediatric patients (Centers for Disease Control classifications P0, P1, and P2), as well as in age-matched normal subjects. Both beta 2-microglobulin and neopterin were significantly increased in HIV-1-infected symptomatic subjects (P2) compared to controls. Seventy-five percent of asymptomatic patients (P1) also had increased values. On the other hand, a significant overlap in concentrations of both markers in serum was found between controls and P0 patients. Thirty-eight percent of the P0 patients had values comparable to those of the P2 group. Persistently high concentrations of both markers in P0 patients may be indicative of HIV-1 infection. PMID- 2229345 TI - Short prereduced anaerobically sterilized (PRAS) biochemical scheme for identification of clinical isolates of bile-resistant Bacteroides species. AB - The rapid identification of isolates of bile-resistant Bacteroides species has clinical and therapeutic relevance because of differences in their patterns of susceptibility and virulence. Five hundred twenty-one strains of bile-resistant Bacteroides species that were previously identified by conventional biochemical methods were reexamined to determine the minimum essential parameters necessary for correct identification. Rapid tests for bile resistance, indole production, and catalase were combined with a novel scheme for biochemical determination of saccharolytic activity on arabinose, trehalose, rhamnose, and/or xylan that included the postincubation addition of bromthymol blue for visual pH determination. Organisms were inoculated into prereduced anaerobically sterilized (PRAS) carbohydrates directly from plates, and identification was complete within 24 h of obtaining a pure culture. Ninety-three percent of bile-resistant Bacteroides species from routine clinical specimens were identified correctly by this scheme; a small number of other indole-positive strains, B. splanchnicus, B. eggerthii, and B. stercoris, were misidentified as B. uniformis. PMID- 2229346 TI - Occurrence of Clavispora lusitaniae, the teleomorph of Candida lusitaniae, among clinical isolates. AB - Of 13 clinical isolates of Candida lusitaniae from diverse geographical regions, 7 represented the mating types (6 alpha, 1 a) of the ascomycete Clavispora lusitaniae. Selected nonfertile isolates showed significant DNA relatedness (greater than 90%) to representatives of both mating types. Phenotypic physiological characteristics, such as cellobiose fermentation and rhamnose assimilation, proved insufficient for separation of Clavispora lusitaniae and Clavispora opuntiae. PMID- 2229347 TI - Electrophoretic analysis of the surface components of autoagglutinating surface array protein-positive and surface array protein-negative Aeromonas hydrophila and Aeromonas sobria. AB - The protein and lipopolysaccharide (LPS) compositions of 10 autoagglutinating Aeromonas hydrophila and Aeromonas sobria strains were studied; one group consisted of five serogroup O:11 strains that contained an S layer, while a second group was composed of diverse serogroups that were S layer negative by transmission electron microscopy. All serogroup O:11 strains were found to contain a predominant 52,000- to 54,000-molecular-weight protein that was present on both whole-cell and outer membrane protein profiles; this protein was found to be glycine extractable under low-pH (pH 4) conditions and was identified as the surface array protein. LPS analysis revealed that all O:11 strains exhibited homogeneous-length O-polysaccharide side chains characterized primarily by two or three major bands. In contrast, S-layer-negative autoagglutinating strains of other serogroups lacked this predominant surface array protein, and silver stain analysis of LPS indicated that such profiles mainly consisted of core antigens and were deficient in or devoid of O-polysaccharide side chains. These collective results offer potential explanations for observed differences between these two groups in virulence, disease spectrum, and pathogenic properties. PMID- 2229348 TI - Application of monoclonal antibodies to the detection of black-pigmented Bacteroides spp. in subgingival plaques by immunoslot blot assay. AB - The aim of the present study was to assess the application of monoclonal antibodies to the detection of black-pigmented Bacteroides spp. in subgingival plaques by immunoslot blot assay. Subgingival plaque samples from adult periodontal patients were examined by immunoslot blot assay with monoclonal antibodies that specifically recognize Bacteroides gingivalis, Bacteroides intermedius serogroups I and II, and Bacteroides melaninogenicus. The assay can detect specifically these Bacteroides spp. in the subgingival plaques. Therefore, we investigated the distribution of these Bacteroides spp. in the subgingival plaques of patients classified by Russell's periodontal index. Reactivities of their plaques with monoclonal antibodies toward B. gingivalis and B. intermedius serogroup I were clearly related to the severity of the periodontal disease, but this was not the case with B. intermedius serogroup II and B. melaninogenicus. These results indicate that this immunoslot blot assay using monoclonal antibodies toward these Bacteroides spp. provides simple detection and monitoring of these organisms in periodontal patients. PMID- 2229349 TI - Phagocytosis of mastitis isolates of Staphylococcus aureus and expression of type 5 capsular polysaccharide are influenced by growth in the presence of milk. AB - Phagocytosis by bovine polymorphonuclear granulocytes of seven capsular polysaccharide type 5 Staphylococcus aureus strains isolated from mastitis [corrected] was investigated by means of luminol-dependent chemiluminescence. Bacteria were grown on four different agar media (brain heart infusion, Columbia broth, modified staphylococcus medium 110, and skim milk) and were opsonized by normal bovine serum. When compared to growth on brain heart infusion agar, Columbia agar, and modified staphylococcus medium 110 agar, growth on skim milk agar rendered five of the strains more resistant to opsonization. The other two strains were resistant in all culture media used. Short periods of incubation in milk after growth on brain heart infusion agar did not augment resistance to phagocytosis, indicating that mere adsorption of milk components on bacteria was not responsible. The variability of the chemiluminescence response of polymorphonuclear leukocytes was pronounced among strains with each growth medium except milk. Growth on modified staphylococcus medium 110 and on milk agar favored the masking of teichoic acid, as shown by inagglutinability with rabbit antiserum. Interestingly, agglutination by a monoclonal antibody to capsular polysaccharide type 5 was optimal when bacteria were grown on skim milk agar. This suggests that capsular polysaccharide participated in the masking effect. These findings indicate that masking of the bacterial target of most of the naturally acquired opsonins present in normal bovine serum occurred when bacteria grew in the presence of milk, resulting in an increased resistance to phagocytosis by polymorphonuclear leukocytes. PMID- 2229350 TI - Detection of colonization factor antigen I-positive enterotoxigenic Escherichia coli with a cloned polynucleotide probe. AB - We compared a new colony hybridization assay with an established enzyme-linked immunosorbent assay for detection of enterotoxigenic Escherichia coli (ETEC) expressing colonization factor antigen I (CFA/I). The tests were applied to 135 human ETEC strains. Of these isolates, 30 had previously been characterized for CFAs. A strain harboring the plasmid vector of the polynucleotide gene probe, nine non-ETEC strains from healthy infants, and eight ETEC strains of animal origin were included for further evaluation of probe specificity. The two assays showed a high level of concordance in the specific detection of ETEC strains expressing CFA/I. A total of 24 strains tested positive in the CFA/I hybridization assay, while 23 of those strains were positive in the CFA/I enzyme linked immunosorbent assay. The single discrepant result could be explained by the loss of a regulatory gene. The strain harboring the plasmid vector of the probe, the non-ETEC E. coli strains, and the ETEC strains of animal origin were all negative in the CFA/I probe assay. PMID- 2229351 TI - Biochemical and serological characterization of Bacteroides intermedius strains isolated from the deep periodontal pocket. AB - Fifty-one fluorescence-positive black-pigmented Bacteroides strains obtained from 51 patients with deep periodontal pockets (greater than 6 mm) were identified and characterized. Fifty of these strains were presumptively identified as Bacteroides intermedius according to the indole reaction. This was confirmed by further biochemical characterization. The 50 strains from diseased sites were then compared with 16 B. intermedius strains isolated from periodontally healthy individuals with no signs of destructive periodontal disease. Tests for antimicrobial susceptibility showed similar patterns for all 50 pocket-derived strains, except for one beta-lactamase-positive strain that was resistant to penicillin G and ampicillin. Forty-seven strains were tested for binding of three monoclonal antibodies defining three distinct serogroups of B. intermedius. Thirty-one strains belonged to serogroup I, three to serogroup II and thirteen to serogroup III. In comparison to the strains from the shallow periodontal pockets, serogroup I was significantly overrepresented in the patient group with periodontal disease. We conclude that saccharolytic black-pigmented Bacteroides species from deep periodontal pockets constituted, with very rare exceptions, a biochemically homogeneous but antigenically heterogeneous group of B. intermedius and that serogroup I is predominantly found in deep periodontal lesions. PMID- 2229352 TI - Identification of a double-stranded RNA virus by using polymerase chain reaction and magnetic separation of the synthesized DNA segments. AB - A double-nested polymerase chain reaction assay (PCR), followed by magnetic separation of the PCR-synthesized DNA segments, was developed to detect a double stranded RNA virus, infectious pancreatic necrosis virus from salmonid fish. Viral RNA was extracted from cell cultures and used for cDNA synthesis. The cDNA produced was used as a template in a double PCR. The sensitivity of this double PCR was approximately 0.8 pg of template double-stranded RNA. The DNA segment produced from the first PCR was also used as a template in a second PCR with a set of two 5'-labeled primers, one with biotin and the other with 32P. The PCR segment that was then synthesized was separated from the solution by using streptavidin-coated, superparamagnetic beads. The levels of radioactivity measured in the magnetically separated fractions were significantly higher in the positive samples than they were in the negative samples. PMID- 2229353 TI - Evaluation of two monkey species (Macaca mulatta and Macaca fascicularis) as possible models for human Helicobacter pylori disease. AB - Endoscopic, histologic, and microbiologic evaluations of 21 cynomolgus and 34 rhesus monkeys for naturally occurring Helicobacter pylori infection were done. H. pylori was never isolated from any cynomolgus monkey, but was found in 12 rhesus monkeys. A general correlation existed between a positive culture and a gastric inflammatory response. Inoculation challenges were then undertaken. Four cynomolgus and five rhesus monkeys received two different H. pylori strains isolated from humans. Five rhesus monkeys received an isolate obtained from rhesus monkeys. Evaluation of the cynomolgus monkeys 7 and 14 days later revealed no H. pylori. Endoscopies of the rhesus monkeys were done 7, 14, 21, 28, and 56 days later. One rhesus monkey, which received the isolate from humans, became H. pylori positive at day 21 and remained positive through day 56. Restriction enzyme analysis of genomic DNA at day 56 revealed that the isolate was not identical to the challenge strain isolated from humans. All five rhesus monkeys that received the strain isolated from rhesus monkeys became H. pylori positive by day 14 and remained positive through day 56 Antral inflammation developed in all monkeys. Restriction enzyme analysis of genomic DNA on day 56 confirmed that four of five isolates were identical to the challenge strain isolated from rhesus monkeys. DNA hybridization documented homology between the challenge strains isolated from humans and rhesus monkeys plus those isolated at day 56. In this study, we showed that the rhesus monkey, if given a strain of H. pylori isolated from rhesus monkeys, develops a gastric infection with accompanying histological changes, making this model suitable for further development. PMID- 2229354 TI - Impact on routine diagnosis of echovirus infections of intratypic differentiation and antigenic variation in echovirus type 25 studied by using monoclonal antibodies. AB - We studied the biological and antigenic properties of wild strains of echovirus type 25 isolated in France between 1982 and 1987 and compared them with the JV-4 prototype strains isolated in 1957. The wild strains differed from the prototype strain in their cellular tropism. The prototype strain grew readily in five cell lines (MRC5, MA 104, Vero, BGM, and HT 29-18), while for wild strains MRC5 and HT 29-18 cells were the most sensitive and supported growth to high titres (between 4.5 and 7.4 50% tissue culture infective doses per 0.05 ml). Plaques produced by wild strains were larger (6.05 +/- 0.94 mm in diameter [mean +/- standard deviation]) than those of the prototype strain (2.3 +/- 0.97 mm in diameter) and heterogeneous, even after cloning by three terminal dilution passages, which suggested heterogeneous virus populations. Virus neutralization with polyclonal monovalent sera showed that wild strains were significantly less neutralized by two reference immune sera than the prototype strain was. Monoclonal antibodies were raised against the echovirus type 25 JV-4 prototype strain. Nine clones with neutralizing activity were identified. Heterologous neutralizations of 14 clinical isolates revealed highly conserved, moderately conserved, and poorly conserved epitopes. The natural isolates differed from the prototype strain in two to four epitopes and can be classified into four different groups. We concluded that echovirus type 25, like coxsackie- and polioviruses, consists of heterogeneous viral populations with respect to biological and antigenic properties. In term of viral diagnosis, it may become increasingly difficult to identify recently isolated strains because of their antigenic variation. PMID- 2229355 TI - Rapid prenatal diagnosis of congenital Toxoplasma infection by using polymerase chain reaction and amniotic fluid. AB - Infection of pregnant women with Toxoplasma gondii places the developing fetus at risk for congenital infection. We report a prospective study of 43 documented cases of acute maternal Toxoplasma infections acquired during gestation in which the polymerase chain reaction (PCR) was evaluated for diagnosis of fetal infection and compared with the current standard methods. On the basis of direct lysis of pelleted amniotic fluid cells followed by amplification of a gene sequence specific for T. gondii, PCR correctly identified the presence of T. gondii in five of five samples of amniotic fluid from four proven cases of congenital infection. PCR also detected three of five positive cases from a nonprospective group. The two diagnostic methods of comparable speed, detection of specific immunoglobulin M from fetal blood and and inoculation of amniotic fluid into tissue culture, correctly identified only 3 and 4 of the 10 positive samples, respectively. The considerably more time-consuming methods of mouse inoculation of amniotic fluid and fetal blood both detected 7 of 10 positive samples. There were no false-positive diagnoses by any of the methods. Therefore, detection of T. gondii by PCR appears to be the most promising method for prenatal diagnosis of congenital Toxoplasma infection, since it is both extremely rapid and highly sensitive. PMID- 2229356 TI - Serological typing of spotted fever group Rickettsia isolates from Zimbabwe. AB - Eight rickettsialike organisms were isolated in tissue culture from ticks of dogs and cattle from various areas of Zimbabwe. These isolates and a reference strain, Rickettsia conorii Simko, were tested by microimmunofluorescence against homologous and heterologous antisera raised in mice. From the titers obtained by this method, specificity differences (SPDs) were calculated between each of the rickettsiae. Only small serological differences were detected among the isolates from ticks obtained from dogs (mean SPD, 0.5) and also among the isolates from ticks obtained from cattle (mean SPD, 0.3). However, when isolates from ticks obtained from dogs and cattle were compared, the serological differences were greater (mean SPD, 1.3). The isolates from ticks obtained from dogs were found to be very similar serologically to the Simko strain of R. conorii (mean SPD, 0.8), while three of four isolates from ticks obtained from cattle were different enough (SPD, greater than or equal to 3) to be identified as separate serotypes. These findings indicate that there is a high degree of antigenic heterogeneity among the tick-transmitted spotted fever group rickettsiae in Zimbabwe. PMID- 2229357 TI - Bovine lactoferrin binding to six species of coagulase-negative staphylococci isolated from bovine intramammary infections. AB - Bovine lactoferrin (BLf), an acute-phase iron-binding secretory protein present in secretions of the bovine udder, was demonstrated to bind to the following staphylococcal species associated with bovine intramammary infections: S. epidermidis, S. warneri, S. hominis, S. xylosus, S. hyicus, and S. chromogenes. The degree of 125I-labeled BLf uptake significantly varied among the blood agar grown cells of all six species of coagulase-negative staphylococci tested. Isolates identified as S. xylosus demonstrated the highest (mean, 35.1 x 10(6) +/ 13.3 x 10(6) nmol) and S. hyicus the lowest (mean, 10.7 x 10(6) +/- 5.9 x 10(6) nmol) binding to 125I-BLf. BLf binding was optimum at an acidic pH, with time dependent binding saturation ranging from 70 min for S. warneri to 240 min for S. hominis. The BLf-binding mechanism was specific, with affinity constants (Ka values) ranging between 0.96 x 10(6) and 11.90 x 10(6) liters/mol. The numbers of BLf-binding sites per cell, as determined by using Scatchard analysis, were as follows: S. epidermidis, 3,600; S. warneri, 1,900; S. hominis, 4,100; S. xylosus, 4,400; S. hyicus, 6,100; and S. chromogenes, 4,700. 125I-BLf binding to all species was inhibited by unlabled BLf and unlabeled human lactoferrin, whereas none of the various plasma, connective tissue, or mucosal secretory proteins or carbohydrates tested caused significant interference. BLf-binding receptors of the six coagulase-negative staphylococcal species demonstrated marked differences in patterns of susceptibility to proteolytic or glycolytic enzyme digestion and to heat or periodate treatment. These data suggest that the BLf-binding components in S. epidermidis and S. warneri are proteins containing glycosidyl residues. In the remaining four species, the proteinaceous nature of the BLf binding component was evident, but the involvement of glycosidyl residues was not clear. Results of this study establish the presence of specific binding components for BLf on coagulase-negative staphylococci isolated from bovine intramammary infections. PMID- 2229358 TI - Nonvalue of antigen detection immunoassays for diagnosis of candidemia. AB - We evaluated the Cand-Tec (Ramco Laboratories Inc., Houston, Tex.) and LA-Candida antigen detection system (Immuno-Mycologics Inc., Norman, Okla.) tests as possible rapid alternatives to blood cultures for the identification of patients with candidemia. Tests were performed on sera from (i) 33 patients with candidemia, (ii) 82 patients with fever and risk factors for invasive candidiasis, and (iii) 13 healthy controls. A total of 21 patients had no evidence of invasive candidiasis, as determined by clinical course, blood culture, and/or autopsy; results for 61 patients were indeterminate regarding the presence of invasive candidiasis, or else the patients had invasive candidiasis with organ involvement. By using a threshold positive Cand-Tec titer of greater than or equal to 1:4, the sensitivity in candidemic patients was 49%; the specificity was 43% (patients with true-negative results had neither candidemia nor other evidence of invasive candidiasis). Coexistent disseminated candidiasis in some candidemic patients may have accounted for some positive Cand-Tec tests and possible overestimation of the sensitivity of the test for candidemia. Cand Tec test results were negative for healthy controls. All test results obtained by the LA-Candida antigen detection system assay were negative. Our findings indicate that neither of these assays reliably identifies patients with candidemia. PMID- 2229359 TI - Production of hemolysin and other extracellular enzymes by clinical isolates of Pseudomonas pseudomallei. AB - One hundred clinical isolates of Pseudomonas pseudomallei from humans were tested for their ability to produce extracellular, biologically active substances which are thought to contribute to the virulence of Pseudomonas species. All isolates produced at least on extracellular enzyme; 91 strains were positive for lecithinase, lipase, and protease; but none was positive for elastase. Ninety three strains produced a hemolysin which was detectable around the heavy growth on saline-washed sheep erythrocyte brain heart infusion agar but not demonstrable around individual colonies or in broth culture filtrate. In contrast, a hemolysin which was cytolytic around individual colonies of P. pseudomallei on the assay plate and in broth culture filtrate was exhibited by four strains. By using one of these four isolates as the test strain, the latter hemolysin was characterized further. It was heat labile, most active in an acid environment (pH 5.5), and cytolytic in broth culture filtrate for a variety of animal and human erythrocytes. Sterols, particularly cholesterol and 7-dehydrocholesterol, inhibited its hemolytic activity, but the activity was not enhanced by reducing agents or suppressed by reagents which modify sulfhydryl-activated hemolysins. A nonhemolytic mutant of the test strain of P. pseudomallei retained the extracellular enzymes of its parent, indicating that the hemolysin was not a lecithinase, lipase, or protease. PMID- 2229360 TI - Evaluation of the indoxyl acetate hydrolysis test for rapid differentiation of Campylobacter, Helicobacter, and Wolinella species. AB - A total of 410 well-defined Campylobacter, Helicobacter, and Wolinella strains, comprising 26 named species, subspecies, and defined groups, were tested for indoxyl acetate hydrolysis by a disk method by using disks prepared at the Centers for Disease Control, Atlanta, Ga. All C. coli (43 strains), C. cryaerophila (34 strains), C. fennelliae (5 strains), C. fennelliae-Campylobacter like organism 3 (2 strains), C. jejuni (66 strains), C. jejuni subsp. doylei (3 strains), hippurate-negative C. jejuni-C. coli (15 strains), "C. upsaliensis" (39 strains), H. mustelae (5 strains), W. curva (1 strain), and W. recta (1 strain) hydrolyzed indoxyl acetate. Four strains gave weak positive reactions, and the remaining 196 strains, which belonged to 15 species, subspecies, and defined groups, gave negative reactions. Of the 410 study strains, 246 and 125 strains were tested for indoxyl acetate hydrolysis by a disk method and a tube method, respectively, by using commercially produced disks. The disk method, regardless of source, required less time and interpretation than the tube method did. Better differentiation between Campylobacter spp. was obtained with the indoxyl acetate test than with the trimethylamine N-oxide test. The indoxyl acetate disk distinguished C. lari from C. jejuni and C. coli, C. cinaedi from C. fennelliae, and H. pylori from H. mustelae and suggested that W. succinogenes could be differentiated from W. recta and W. curva. The indoxyl acetate disk method could be performed in 5 to 30 min, was easy to read and interpret, and should be useful as a routine diagnostic test for identification of Campylobacter spp. PMID- 2229361 TI - Identification of Giardia lamblia-specific antigens in infected human and gerbil feces by western immunoblotting. AB - Western immunoblot analysis of aqueous extracts of feces obtained from five giardiasis patients and from experimentally infected gerbils (Meriones unguiculatus) with rabbit antiserum to Giardia lamblia cysts has revealed antigens of three molecular weight groups. A stepladderlike, evenly-spaced set of strongly reactive antigens (darkest at a molecular weight [m.w.] of 55,000 to 70,000) appeared in the gerbil feces from day 4 (first experiment) or day 2 (second experiment) and lasted to about day 7 but disappeared completely by day 8 and did not reappear later. These antigenic bands were seen in gerbils infected with two isolates of G. lamblia. These bands were not revealed when antiserum to trophozoites was used as the probe, nor were they evident in specimens from the patients or in a preparation of sonicated cysts. A second group of antigens, represented by two to three low-m.w. bands of approximately 15,000 to 20,000, was evident in both the blots of gerbil feces after approximately day 8 and the specimens from the giardiasis patients. The third group of antigens revealed by blotting experiments was a high-m.w. band (approximately 110,000) which appeared on a number of days (beginning of day 8 of gerbil infection), but this band was not seen in the human specimens. A clear band corresponding to the previously reported GSA-65 antigen was not seen in either the gerbil or the human samples. Some low- and high-m.w. bands were also detected by antitrophozoite serum in the gerbil samples, but these were weak and unimpressive compared with those visualized using anticyst serum. A monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay revealed that Giardia spp.-specific stool antigen rose suddenly at day 3 of gerbil infection, at the time when fecal cyst numbers began to rise rapidly. PMID- 2229362 TI - Differentiation of genes coding for Escherichia coli verotoxin 2 and the verotoxin associated with porcine edema disease (VTe) by the polymerase chain reaction. AB - Two sets of synthetic oligonucleotide primers were used in a polymerase chain reaction adaptation to distinguish the closely related genes for type 2 verotoxin (VT2 or Shiga-like toxin [SLT-II]) and the verotoxin associated with porcine edema disease (VTe or SLT-II variant [SLT-IIv]) in Escherichia coli. PMID- 2229363 TI - Importance of membrane-bound antigens of Toxoplasma gondii and their fixation for serodiagnosis of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome. AB - Titers in a direct agglutination test using Formalin-fixed toxoplasma tachyzoites were significantly higher in patients with acquired immunodeficiency syndrome with toxoplasmic encephalitis (TE) than in those without TE. In contrast, when fresh (not fixed) tachyzoites were used, the titers did not differ from those in patients without TE. The direct agglutination test using Formalin-fixed tachyzoites better distinguished between patients with TE and those without TE than an agglutination test using latex particles coated with Formalin-fixed sonicated-tachyzoite antigens. Thus, both selective use of membrane-bound antigens and their fixation are important for serodiagnosis of TE in patients with acquired immunodeficiency syndrome. PMID- 2229364 TI - Microbiological characteristics of Weeksella virosa (formerly CDC group IIf) isolated from the human genitourinary tract. AB - Weeksella virosa (formerly CDC group IIf) is a nonsaccharolytic, oxidase- and catalase-positive, gram-negative rod which is unable to grow on MacConkey agar. At 48 h of incubation on blood or chocolate agar, the colonies present a characteristic appearance: intensely mucoid, adherent, and cream colored as a result of the production of a nondiffusible yellow pigment. This microorganism has been isolated predominantly from the female genitourinary tract, which indicates the opportunity for sexual transmission. We present the microbiological study of three strains of W. virosa identified in a study of 707 female genital samples, representing an incidence of 0.42%. At the same time, we analyzed the principal biochemical tests used in the identification of this microorganism and the susceptibilities of the organism to the different antimicrobial agents assayed. PMID- 2229365 TI - Aerobic bacteria cultured from the mouth of the American opossum (Didelphis virginiana) with reference to bacteria associated with bite infections. AB - The American opossum inflicts bite injuries both when hunted for food and when accidentally provoked when handled in captivity. This study involved aerobically culturing organisms from the mouths of seven wild opossums (Didelphis virginiana). Isolates included streptococci, coagulase-positive and -negative staphylococci, Aeromonas spp., Citrobacter freundii, Eikenella corrodens, and Escherichia coli. PMID- 2229366 TI - Campylobacter-like organisms are uncommon pathogens in patients infected with the human immunodeficiency virus. AB - Over a 25-month period, we prospectively evaluated 36 patients with symptomatic human immunodeficiency virus disease (including 27 with unexplained chronic diarrhea) by flexible sigmoidoscopy for the presence of Campylobacter-like organisms. No Campylobacter-like organisms were isolated. Campylobacter-like organisms appear to be an uncommon cause of idiopathic chronic diarrhea in symptomatic human immunodeficiency virus disease. PMID- 2229367 TI - Microagglutination test for early and specific serodiagnosis of tularemia. AB - A microagglutination test with safranin-stained Francisella tularensis antigen was compared with a conventional tube agglutination test for the serodiagnosis of tularemia. The microagglutination test was performed in round-bottom microtiter plates by using 0.025 ml of the antisera and of the antigen. The antibody titers obtained by using the microagglutination test were 8 to 64 times higher than those seen with the tube agglutination. By the microagglutination test, the serum agglutinins were detected 3 days earlier in rabbits and 9 days earlier in humans than by the tube agglutination test. The microagglutination test also detected residual circulating antibodies in humans more than 20 years after recovery from infection. These early agglutinins were shown to be in the immunoglobulin M class because of their sensitivities to 2-mercaptoethanol. No significant group agglutination reaction with Brucella abortus was observed. These observations indicate that the microagglutination test is a useful tool for the early and specific serodiagnosis of tularemia. PMID- 2229368 TI - Eubacterium lentum ATCC 43055, a new reference strain for quality control of anaerobic susceptibility tests. AB - A strain of Eubacterium lentum (ATCC 43055) was selected for quality control of anaerobic susceptibility tests. Multilaboratory collaborative studies with 13 different antimicrobial agents were reviewed, and MIC control limits were proposed for agar dilution tests with the new control strain. PMID- 2229369 TI - Clostridium septicum as a cause of pericarditis and mycotic aneurysm. AB - Clostridium septicum is a bacterial species associated with gas gangrene in both humans and animals. Although not usually a pathogen in humans, it has been implicated in some cases of abscesses and bacteremia. We now report the first case of pericarditis with mycotic aneurysm due to C. septicum. PMID- 2229370 TI - Selective staphylococcal broth. PMID- 2229371 TI - Reproducibility and indices of discriminatory power of microbial typing methods. AB - When microbial strain-typing methods are compared, the most important characteristics are typeability, reproducibility, and discriminatory power. While typeability and reproducibility can be presented as numerical values, indices of discriminatory power have only recently been described. This paper examines the relationship between reproducibility and indices of discriminatory power. In an individual typing method, an inverse relationship between reproducibility and discriminatory power appears as the number of test differences required in order to distinguish between strains is increased. A method of standardizing the discriminatory power of a typing method to a predetermined reproducibility is presented. In this way the discriminatory powers of different typing methods can be compared while being standardized for the effect of reproducibility. PMID- 2229372 TI - Rapid and sensitive detection of Mycobacterium leprae using a nested-primer gene amplification assay. AB - By using a set of four nested oligonucleotide primers, a two-step polymerase chain reaction assay for the detection and identification of Mycobacterium leprae that does not require the use of radioactivity labeled hybridization probes was developed. The nested-primer procedure amplified a 347-base-pair product from M. leprae genomic DNA. No amplification products were produced from DNAs of 19 other Mycobacterium species, 19 non-Mycobacterium species, mouse cells, or human cells. Minor amplification products were observed with three additional Mycobacterium species, i.e., "M. lufu", M. simiae, and M. smegmatis. These products were easily distinguished from the M. leprae product by size and restriction enzyme cleavage patterns. The assay could amplify the 347-base-pair product from samples containing as little as 3 fg of M. leprae genomic DNA--the amount of DNA in a single bacillus. The assay also amplified target sequences in crude lysates of M. leprae bacilli isolated from tissue biopsy specimens from infected animals and humans. The entire assay, from sample preparation to data analysis, can be completed in less than 8 h. PMID- 2229373 TI - Clinical comparison of isolator and BACTEC 660 resin media for blood culture. AB - The 10-ml Isolator system (E.I. du Pont de Nemours & Co., Inc., Wilmington, Del.) was compared with the BACTEC 16A-17A nonradiometric resin system (Johnston Laboratories, Inc., Towson, Md.) for isolation of organisms from 6,839 paired blood cultures. Equal volumes of blood (6 to 10 ml for each Isolator and 3 to 5 ml for each BACTEC bottle) were cultured in parallel in the two systems, and 600 isolates that were judged to be clinically significant by chart review were recovered during the study. The BACTEC resin system detected 510 (85%) and the Isolator system detected 435 (72%) of the clinically significant isolates (P less than 0.001). Of 45 polymicrobial blood cultures, the BACTEC system detected 32 (71%) and the Isolator system detected 21 (47%) (P less than 0.05). Of 253 gram negative bacilli isolated during the study, 30% were detected only in the BACTEC system and 16% were detected only in the Isolator system (P less than 0.001), and of 56 nonfermentative or fastidious gram-negative bacilli detected, 46% were recovered only in the BACTEC system, while 14% were detected only in the Isolator system (P less than 0.001). Of 86 streptococci isolated during the study, 30% were detected only in the BACTEC system, and 4% were detected only in the Isolator system (P less than 0.001). Recoveries of anaerobic bacteria, staphylococci, and yeasts were equivalent in the two systems. Organisms judged to be contaminants were detected in approximately 1% of the cultures in each system. The results suggest that use of resin media renders the BACTEC nonradiometric system equivalent or superior to the Isolator system for detection of clinically significant organisms in blood cultures. PMID- 2229375 TI - Oerskovia xanthineolytica implicated in peritonitis associated with peritoneal dialysis: case report and review of Oerskovia infections in humans. AB - Oerskovia species are nocardialike bacteria that have been implicated as pathogens only rarely. These organisms are branched, gram-positive bacilli that are oxidase negative, catalase positive, and non-acid fast. Unlike Nocardia species, these organisms are motile, do not produce aerial mycelia, and possess a cell wall with large amounts of galactose. Colonies are bright yellow and produce branched vegetative hyphae on nutrient agar. A 70-year-old patient undergoing chronic ambulatory peritoneal dialysis for end-stage renal dysfunction developed recurrent peritonitis. Five peritoneal fluid cultures and one catheter specimen obtained over a period of two weeks yielded a gram-positive bacillus; Oerskovia xanthineolytica was isolated from all six cultures. Prolonged systemic therapy with gentamicin and vancomycin was unsuccessful in curing the peritonitis, but the infection resolved following removal of the peritoneal catheter. This is the first reported case of peritonitis associated with this microorganism. A review of previously described Oerskovia infections, most of which were associated with foreign bodies, showed that removal of infected foci was usually necessary for cure. PMID- 2229374 TI - Differential agglutination test for diagnosis of recently acquired infection with Toxoplasma gondii. AB - We evaluated the recently described differential agglutination test (HS/AC test) to differentiate recently acquired toxoplasma infections from those acquired in the more distant past in sera obtained from 38 patients with carefully defined symptomatic and asymptomatic infections. AC antigens detect acute-phase-specific immunoglobulin G (IgG) antibodies against Toxoplasma gondii tachyzoites that are formed only during the acute stage of infection in humans. The HS/AC test correctly identified recently acquired infections in patients with toxoplasmic lymphadenopathy or asymptomatic infections (including infections in 7 women who seroconverted during gestation) in 31 of 33 patients. We also studied 15 individuals who had been infected for at least 2 years. In that group, only 13% had an acute pattern in the HS/AC test. However, the wide range in times from infection (from 2 to 14 years) did not allow for an estimate of when the pattern in the HS/AC test changed from acute to not acute. These results reveal that in the appropriate clinical situation, when both IgG and IgM tests are positive and a question still remains about the acuteness of infection, the HS/AC test may be useful for differentiating between toxoplasma infections acquired recently and those acquired in the more distant past. PMID- 2229376 TI - Evaluation of the updated Vitek yeast identification data base. AB - Using 398 isolates of yeasts and yeastlike fungi comprising 9 genera and 26 species, as well as the hyphomycete Geotrichum candidum and the achlorophyllous alga Prototheca wickerhamii, we compared the API 20C yeast identification system with the modified Vitek yeast identification system with an expanded data base. We found 11 discrepancies between the two systems: five (1.3%) of the isolates (Blastoschizomyces capitatus, 1; Candida albicans, 1; Hansenula anomala, 1; Rhodotorula minuta, 2) had biocodes not included in the expanded Vitek data base, and six (1.5%) of the isolates (Candida lusitaniae, 1; Candida parapsilosis, 1; Cryptococcus uniguttulatus, 1; H. anomala, 1; Torulopsis candida, 2) were misidentified by the Vitek system. Overall, the efficacy of the Vitek system compares favorably with that of the API 20C in the identification of clinically important yeasts. PMID- 2229377 TI - Assessment of conventional and commercial methods for identification of clinical isolates of cysteine-requiring strains of Escherichia coli and Klebsiella species. AB - Cysteine-requiring strains of the family Enterobacteriaceae that are auxotrophic for this amino acid because of defects in the sulfur assimilatory pathway account for about 1.5% of urinary tract isolates of Escherichia coli and Klebsiella species. Forty Escherichia and eight Klebsiella cysteine-requiring strains were used to test the ease with which various test systems identified clinical isolates of cysteine auxotrophs. In a preliminary experiment, the growth yield of 10 cysteine-requiring E. coli in 10 solutions of commercially available peptones was in each instance less than that of prototrophic control and showed that these sources of nutrients were suboptimal for these strains. A significant proportion of the cysteine-requiring strains were not adequately identified by growth dependent tests which used various peptones as a nutrient source. Problems were encountered with all test systems examined, which were as follows: conventional methods; the API 20E, Microbact, and Vitek systems; and two rapid methods for the identification of E. coli, the Rapidec coli and the beta-D-glucuronidase tests. The performance of the test systems was only partly improved when inocula were derived from appropriately supplemented media. However, the problems of the growth-dependent tests were resolved when a cysteine-supplemented suspension was used to inoculate each test system. PMID- 2229378 TI - Molecular cloning of Ehrlichia risticii and development of a gene probe for the diagnosis of Potomac horse fever. AB - A gene bank of Ehrlichia risticii was constructed in plasmid vector pUC13. Five clones representing discrete regions of the E. risticii genome were tested for their ability to hybridize specifically to E. risticii DNA. None of the clones cross-hybridized with Ehrlichia equi DNA, whereas four of these clones cross hybridized with Ehrlichia canis and Ehrlichia sennetsu DNAs. However, one clone carrying a 1-kilobase HindIII fragment of E. risticii DNA failed to cross-react with the genomes of E. sennetsu, E. canis, and E. equi in dot blot hybridization assays. The sensitivity of this probe for the detection of E. risticii DNA was approximately 0.5 pg. By using this probe, the E. risticii DNA was detected in the peripheral blood mononuclear cells of 30 experimentally infected horses by 7 days postinfection (p.i.); the detection of E. risticii DNA peaked between 14 and 17 days p.i., a period immediately after the peak of the second rise in body temperature, during leukopenia and at the onset of diarrhea. E. risticii DNA was not detectable by 25 to 30 days p.i. E. risticii DNA was not detected in noninfected control horses. PMID- 2229379 TI - Diagnosis of Chlamydia trachomatis cervical infection by detection of amplified DNA with an enzyme immunoassay. AB - A sensitive and specific system for detection of amplified Chlamydia trachomatis DNA from cervical specimens by fluorometric quantitation in an enzyme immunoassay (EIA) format (polymerase chain reaction [PCR]-EIA) is described. The primers selected for PCR-amplified DNA were from the 15 serovars of C. trachomatis and two strains of Chlamydia pneumoniae (TWAR). One strain of Chlamydia psittaci (Borg) was not amplified. One hundred four previously cultured cervical specimens were evaluated. Forty-six culture-positive specimens containing from 1+ to 4+ inclusion bodies were all positive by PCR-EIA. Of 58 culture-negative specimens, 2 were repeatedly positive and were nonreactive with control probes. This assay system represents a sensitive and specific combination of technologies for the quantitative detection of C. trachomatis DNA directly from a body fluid. PMID- 2229380 TI - Comparison of four Mycoplasma arthritidis strains by enzyme immunoassay, metabolism inhibition, one- and two-dimensional electrophoresis, and immunoblotting. AB - Four Mycoplasma arthritidis strains, two virulent (158p10p9 and 14124p10) and two avirulent (PG6 and H606), were examined for differences in their antigenic compositions. Rabbit antisera prepared against each strain were compared for their reactivities against both homologous and heterologous strains by enzyme linked immunosorbent assay and metabolism inhibition assay. These tests confirmed a close serologic relationship among the four strains. Only by cross-absorbing each antiserum with intact cells from both homologous and heterologous strains could serologic differences be detected. Interestingly, antigenic variability was minimal among those antigens involved in the metabolism inhibition reaction, suggesting that they may be highly conserved within this species. No differences in protein composition could be detected by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. However, slight variation was apparent on two-dimensional gels, and antigens possessing strain-specific epitopes were detected by two-dimensional immunoblotting experiments performed with cross-absorbed antisera. The enzyme-linked immunosorbent assay, two dimensional electrophoresis, and immunoblotting experiments showed that the two virulent strains were closely related to each other, while the avirulent strains were more distantly related to each other and to the other two strains. The relationship of M. arthritidis serologic diversity to virulence remains unclear: however, this study has demonstrated that it may be possible to subdivide M. arthritidis into serogroups on the basis of cross-absorption patterns and to identify those antigens bearing strain-specific epitopes by immunoblotting with cross-absorbed antisera. PMID- 2229381 TI - Analysis of a repetitive DNA sequence from Bordetella pertussis and its application to the diagnosis of pertussis using the polymerase chain reaction. AB - A tandemly repeated 1,046-base-pair (bp) ClaI DNA fragment from Bordetella pertussis was cloned into Escherichia coli by using the vector pUC19. This fragment, when isolated, hybridized strongly to DNA from all 100 clinical isolates of B. pertussis tested. It was shown to have homology to single-copy sequences in Bordetella bronchiseptica but not Bordetella parapertussis and did not hybridize to lysate blots of a wide range of other bacteria, including members of the closely related genera Pasteurella, Alcaligenes, and Haemophilus. The 1,046-bp fragment was sequenced, and complementary synthetic oligonucleotides flanking a 153-bp region within the repeated element were used as primers for specific amplification of this region using the polymerase chain reaction (PCR). This procedure was then applied to the rapid (5-h) detection of B. pertussis in nasopharyngeal secretions collected from 332 children with suspected pertussis. The test yielded positive results in a total of 98 samples, compared with 66 for culture and 33 for direct immunofluorescence (IF). All of the IF-positive samples were PCR positive, as were 63 of the samples from which B. pertussis was eventually cultured. Two hundred thirty-one specimens which were negative by IF and culture were also negative in the PCR assay. However, 33 culture- and IF negative specimens were positive by PCR assay. Several of these specimens were collected from close contacts of culture-proven pertussis patients, were follow up specimens from such patients, or were from patients with serological evidence of pertussis and therefore may be true-rather than false-positives. PMID- 2229382 TI - Comparison of immunofluorescence, particle agglutination, and enzyme immunoassays for detection of human T-cell leukemia virus type I antibody in African sera. AB - The effectiveness of four screening tests for detecting antibody to human T-cell leukemia virus type I (HTLV-I) was determined by using 2,700 African serum specimens. The tests studied were indirect immunofluorescence, particle agglutination from Fujirebio, and two enzyme immunoassays, one from Abbott Laboratories that used virus lysate from HUT 102 cells and the other from Cambridge BioScience Corp. that used an env recombinant protein. Positive and doubtful sera were confirmed by Western immunoblot and radioimmunoprecipitation assay with Food and Drug Administration seropositivity criteria. The best results were obtained with the two enzyme immunoassays, which were more sensitive (100 and 98.6% [Abbott and Cambridge, respectively]) and more specific (98.7 and 96.5%). Indirect immunofluorescence exhibited difficulties for reading and interpretation. With particle agglutination, prozone was observed for 9 of 78 HTLV-I-positive serum specimens. False-positives in any of the tests were not linked to cross-reactions with human immunodeficiency viruses. However, confirmation tests remain necessary for HTLV-I screening. PMID- 2229383 TI - Identification of Haemophilus aphrophilus and Actinobacillus actinomycetemcomitans by DNA-DNA hybridization and genetic transformation. AB - DNA-DNA hybridization was used to identify clinical isolates as Haemophilus aphrophilus or Actinobacillus actinomycetemcomitans. Some of the isolates were naturally competent for genetic transformation and were also used as DNA recipients for identification of other isolates. The results obtained by hybridization were supported by interstrain-to-intrastrain transformation ratios. Distinction between the closely related species H. aphrophilus and A. actinomycetemcomitans was generally clear-cut by both methods. Distinction of H. aphrophilus and A. actinomycetemcomitans from type and reference strains of a diversity of species in the family Neisseriaceae and other gram-negative species was also demonstrated by both methods. This is the first description of the identification of clinical isolates of H. aphrophilus or A. actinomycetemcomitans by using them as recipients in genetic transformation. The results suggest that this is a reliable system for identification of new clinical isolates belonging to these taxonomic entities. PMID- 2229384 TI - Differentiation of Naegleria fowleri from Acanthamoeba species by using monoclonal antibodies and flow cytometry. AB - Monoclonal antibodies to Naegleria fowleri and Acanthamoeba polyphaga were analyzed by enzyme-linked immunosorbent assay, indirect immunofluorescence microscopy, and fluorescence flow cytometry to assess specificity and cross reactivity with axenically cultured N. fowleri and Acanthamoeba spp. Four monoclonal antibodies to N. fowleri were specific for N. fowleri and had no reactivity to A. polyphaga. Similarly, four monoclonal antibodies to A. polyphaga did not react with N. fowleri. Two of the four monoclonal antibodies to A. polyphaga did not react with other Acanthamoeba spp. tested, while two of the antibodies demonstrated a high degree of cross-reactivity with a putative Acanthamoeba castellanii strain by immunofluorescence microscopy; this was confirmed by fluorescence flow cytometry for one of the antibodies. These monoclonal antibodies were used to identify Acanthamoeba trophozoites in infected brain sections of a patient who died of suspected Acanthamoeba-caused granulomatous amoebic encephalitis, demonstrating potential utility in the direct identification of N. fowleri and Acanthamoeba spp. in clinical specimens. PMID- 2229385 TI - Application of a rapid microplaque assay for determination of human immunodeficiency virus neutralizing antibody titers. AB - To perform a human immunodeficiency virus (HIV) plaque assay in nonadherent host cells, we developed a novel technique in which HIV-infected MT-2 cells were formed into monolayers by centrifugation through molten agarose. Infection, formation of cell monolayers, and enumeration of plaques all took place in 96 well microtiter plates. When this process was preceded by 18 h of incubation of HIV with patient serum samples, neutralizing antibody titers between 1:10 and 1:5,000 could be accurately determined in patient serum samples. In addition to the determination of neutralizing antibody titers (with the use of various serum dilutions and a constant virus concentration), neutralization indices could also be determined with different virus dilutions and a single dilution of patient serum. PMID- 2229386 TI - Reservoir of four organisms associated with bacterial vaginosis suggests lack of sexual transmission. AB - This study consisted of a search for the possible reservoir and mode of spread of the four bacterial vaginosis-associated organisms Mobiluncus mulieris, Mobiluncus curtisii, Mycoplasma hominis, and Gardnerella vaginalis. Their occurrence in rectal, oral, and pharyngeal specimens from women with and without bacterial vaginosis, their male sexual consorts, four homosexual men, and children (altogether, 374 people) was studied. Genital samples were also obtained from all adults. All four organisms were isolated from the rectums of 45 to 62% of women with bacterial vaginosis and 10 to 14% of women without bacterial vaginosis. They also occurred in the rectums of males and children. M. hominis was recovered from the oropharynxes of 12 adults whose sexual consorts had genital occurrences of the organism. Mobiluncus spp. occurred only in the vaginas of women with bacterial vaginosis (97%). The organisms were only infrequently recovered from genital samples from 135 males. Organisms were recovered from the urethras and/or coronal sulci of 10 of 44 male consorts of women with bacterial vaginosis. However, after 2 weeks of condom use during sexual intercourse, only M. hominis remained in the urethra of one man. These findings suggest that the organisms associated with bacterial vaginosis are not spread sexually but colonize the vagina from an endogenous intestinal tract site. The pathophysiological mechanisms leading to bacterial vaginosis in a subpopulation of all women are still unknown. PMID- 2229388 TI - Vancomycin resistance in Staphylococcus haemolyticus causing colonization and bloodstream infection. AB - The increase in the incidence of infections due to beta-lactam-resistant coagulase-negative staphylococci has resulted in expanded use of vancomycin for such infections. Despite this, coagulase-negative staphylococci have remained susceptible to vancomycin in recent years. This report describes a strain of Staphylococcus haemolyticus with increased resistance to vancomycin (MIC, 8.0 to 16 micrograms/ml). S. haemolyticus was initially isolated from a patient with acute leukemia and neutropenia in surveillance throat and stool cultures. The microdilution vancomycin MICs for these isolates were 1.0 to 2.0 micrograms/ml. Subsequent S. haemolyticus isolates from the bloodstream and tracheal aspirate occurred in the setting of prolonged empirical vancomycin therapy. MICs for these isolates were 8.0 to 16 micrograms/ml. Further vancomycin resistance (MIC, 32 micrograms/ml) could be selected for in vitro in all four isolates. Restriction endonuclease analysis of plasmid DNA indicated that the isolates were very closely related and likely to be of the same strain. We conclude that colonization with a vancomycin-susceptible strain of S. haemolyticus was subsequently linked to a nosocomial bloodstream infection with an apparently identical strain with intermediate levels of vancomycin resistance. Prolonged empirical vancomycin therapy was temporally associated with this episode. PMID- 2229387 TI - Detection of Aspergillus antigens associated with invasive infection. AB - Serial urine samples were collected from 33 neutropenic patients, 10 of whom developed invasive aspergillosis (IA) while undergoing bone marrow transplantation or remission induction therapy for leukemia. Concentrated urine samples from the infected patients were subjected to polyacrylamide gel electrophoresis, blotted, and then incubated with antiserum raised to a cell wall extract of Aspergillus fumigatus (anti-CW) or an immunoglobulin G monoclonal antibody to A. fumigatus galactomannan (EBA1). When IA patient urine blots were probed with anti-CW, major bands at 11 and 18 kilodaltons (kDa); intermediate bands at 13, 14, and 29 kDa; and minor bands at 38 and 44 kDa were seen. In contrast, EBA1 showed diffuse staining at molecular masses larger than 45 kDa and a single weak band at 21 kDa. Urine samples from the 23 patients with no evidence of IA were unreactive with both anti-CW and EBA1. These antigen bands are likely to represent immunodominant antigens which are excreted during IA and should play a valuable role in the development of rapid diagnostic tests for aspergillosis. PMID- 2229389 TI - DNA probes for the identification of Nocardia asteroides. AB - DNA probes for the rapid identification of Nocardia asteroides were obtained by constructing a genomic library of strain GUH-2 in the lambda cloning vector EMBL3. Of 50 recombinant clones tested, 2 were identified that hybridized with 31% of the N. asteroides strains in a reference collection without cross hybridization with related members of the Actinomycetales. Additional libraries were then generated from selected strains of N. asteroides that had failed to hybridize with any of the GUH-2 clones. Four additional clones were obtained from these strains which, when pooled, provided DNA probes specific for all of the N. asteroides strains tested. PMID- 2229390 TI - High-performance liquid chromatography patterns of mycolic acids as criteria for identification of Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium smegmatis. AB - Rapidly growing mycobacteria of clinical significance were identified by mycolic acids detected with high-performance liquid chromatography. Mycolic acids from whole cells were extracted, derivatized, and detected by a modified high performance liquid chromatography procedure in less than 3 h. Use of an internal standard allowed differentiation of Mycobacterium chelonae and Mycobacterium fortuitum by comparison of relative retention times. Peak height ratios were used for subidentification of M. chelonae strains; however, M. fortuitum and Mycobacterium smegmatis could not be separated by this system. PMID- 2229391 TI - Arylsulfatase activity for differentiating Mycobacterium avium and Mycobacterium intracellulare. AB - Arylsulfatase activities (96-h reaction) of various strains of Mycobacterium avium and M. intracellulare, as identified by a DNA probe test, were measured. The enzyme activities of M. avium strains were significantly lower [corrected] than those of M. intracellulare strains (P less than 0.005 to P less than 0.025). The enzyme activities did not vary with serovar; that is, the activities of serovars 1, 2, 8, and 9 (belonging to M. avium) were similar to each other, as were the activities of serovars 7, 12, 13, 14, and 16 (belonging to M. intracellulare). The results indicate the usefulness of the arylsulfatase test in distinguishing M. avium from M. intracellulare in an accurate manner. PMID- 2229393 TI - Bacillus species pseudobacteremia traced to contaminated gloves used in collection of blood from patients with acquired immunodeficiency syndrome. AB - Ten nonpathogenic Bacillus isolates were obtained from blood cultures collected over a 2-year period. Eight of these isolates were from patient with acquired immunodeficiency syndrome, and seven were recovered from blood cultures obtained in outpatient clinics. Five cases occurred during a 5-month period. These five cases were clinically evaluated, and the Bacillus isolates were characterized. The same Bacillus species was isolated from nonsterile gloves from the same lot worn by phlebotomists for blood collection in the outpatient clinics during this period, implicating the gloves as the cause of this pseudoepidemic. Awareness of the nonsterile nature of gloves used by laboratory personnel should be considered in the evaluation of Bacillus spp. in blood cultures. PMID- 2229392 TI - Immunoprecipitation of human immunodeficiency virus type 2 glycoproteins by sera positive for human immunodeficiency virus type 1. AB - Analysis by radioimmunoprecipitation of serum samples from 27 different human immunodeficiency virus type 1 (HIV-1)-infected individuals residing in Chile showed that the sera of 26% of these individuals also react with glycoprotein gp125 of HIV type 2 (HIV-2). This cross-reaction seems to reflect a qualitative difference among infected individuals, because the titer of antibodies against gp120 of HIV-1 in the cross-reacting samples did not differ significantly from that in the non-cross-reacting samples. Most of the HIV-1-seropositive sera, including many that did not react with gp125 of HIV-2, reacted with gp140, the precursor of HIV-2 glycoproteins. The observed cross-reactions allowed us to distinguish three groups of HIV-1-infected individuals: (i) those whose sera react with both gp140 and gp125, (ii) those whose sera react with gp140, and (iii) those whose sera react with neither of these glycoproteins. The possible cause and significance of these differences is under study. PMID- 2229394 TI - Use of modified norleucine-tyrosine broth in identification of Peptostreptococcus anaerobius. AB - Gas-liquid chromatography was employed to analyze the volatile and nonvolatile acids produced in modified norleucine-tyrosine (MNT) broth by various gram positive cocci. The MNT broth consists of 0.5% Trypticase (BBL Microbiology Systems, Cockeysville, Md.), 0.5% yeast extract (Difco Laboratories, Detroit, Mich.), 0.2% L-norleucine, and 0.1% L-tyrosine. The microorganisms included reference strains and clinical isolates of Peptostreptococcus spp. (P. anaerobius, P. asaccharolyticus, P. indolicus, P. magnus, and P. prevotii), Staphylococcus spp. (S. aureus, S. epidermidis, and S. saccharolyticus), and Streptococcus spp. (S. agalactiae, S. intermedius, S. mutans, S. sanguis I, and S. sanguis II). Only Peptostreptococcus anaerobius strains produced caproic and valeric acids in MNT broth cultures. All 11 P. anaerobius strains produced valeric acid in MNT broth, and only 1 strain failed to produce caproic acid in the medium. This unique feature aids in rapid, reliable identification of P. anaerobius with a minimum number of tests. PMID- 2229395 TI - Comparison of alkaline phosphatase-conjugated oligonucleotide DNA probe with the Sereny test for identification of Shigella strains. AB - We compared an alkaline phosphatase-conjugated oligonucleotide DNA probe with the Sereny test to determine the sensitivity and specificity of the probe in detecting virulent Shigella strains. The probe hybridized with all 52 Sereny-test positive strains (sensitivity, 100%) and 4 of 21 Sereny-test-negative strains (specificity, 81%). The probe did not hybridize with any of the Sereny-test negative S. dysenteriae type 1 strains. This nonradioactive, synthetic probe provides a simple, rapid way to test a large number of strains simultaneously in a field setting, which will contribute to an improved understanding of the epidemiologic patterns of shigellosis in developing countries. PMID- 2229396 TI - Meningitis in a neonate caused by Leuconostoc sp. AB - A case of meningitis in a neonate caused by vancomycin-resistant Leuconostoc mesenteroides is presented. This case was complicated by severe ventriculitis and was ultimately fatal. Infection with Leuconostoc spp. is rare but should be suspected when vancomycin-resistant organisms resembling streptococci are isolated. Previous reports of this infection are reviewed. PMID- 2229397 TI - Aerotolerant Clostridium tertium brain abscess following a lawn dart injury. AB - A young girl developed an intracranial abscess and necrotizing cellulitis following penetrating injury from a lawn dart. Initial identification of a gram positive rod growing aerobically from clinical specimens was as a Bacillus organism, but the observation that the isolate grew poorly in subcultures for susceptibility testing but quite well under standard anaerobic culture techniques led to the identification of the organism as an aerotolerant Clostridium tertium. Early management of penetrating head trauma should include cranial imaging studies to detect fractures and intracranial pathology. Clinical microbiologists and clinicians should be aware of the phenomenon of aerotolerance in anaerobic bacteria to avoid errors in choice of antibiotic therapy. PMID- 2229398 TI - Quantitation of human immunodeficiency virus DNA by using the polymerase chain reaction. AB - The polymerase chain reaction was used to measure the DNA copy number of human immunodeficiency virus (HIV). Differences in polymerase chain reaction amplification efficiency were controlled by amplifying known amounts of HIV DNA in parallel with samples. This technique is a sensitive, accurate, and reproducible method for the quantitation of HIV DNA. PMID- 2229399 TI - Western immunoblot and flagellum enzyme-linked immunosorbent assay for serodiagnosis of Lyme borreliosis. AB - Western immunoblot with a whole-cell lysate was compared with an enzyme-linked immunosorbent assay with a purified flagellum antigen of Borrelia burgdorferi for serodiagnosis of Lyme borreliosis. The assays showed similar sensitivities and specificities in detecting immunoglobulin M and/or immunoglobulin G antibodies in sera from 68 patients with neuroborreliosis and 44 controls with meningitis and encephalitis or with multiple sclerosis. Flagellum enzyme-linked immunosorbent assay is more easily standardized and seems to be a more suitable diagnostic test in a routine laboratory. PMID- 2229400 TI - Burn wound zygomycosis caused by Apophysomyces elegans. AB - A case of zygomycosis caused by Apophysomyces elegans in a patient having 25% full-thickness burns is described. Amputation of the leg was necessary to control rapid tissue invasion. The fungus was isolated from soil in the burn environment. PMID- 2229401 TI - Evaluation of monoclonal antibody F9-4 as immunological probe for Leptospira interrogans. AB - I assayed the lack of reactivity of monoclonal antibody (MAb) F9-4 with nonpathogenic leptospires. Of 47 saprophytic strains tested, 46 did not react in an enzyme immunoassay and 1 was recognized by MAb F9-4, as usually reported with pathogenic Leptospira strains. On the other hand, the MAb did not react with one pathogenic strain, thus showing that the ability of MAb F9-4 to discriminate between pathogenic and nonpathogenic leptospires is not absolute. PMID- 2229402 TI - Evaluation of different techniques for detection of virulence in Yersinia enterocolitica. PMID- 2229403 TI - Increased proliferation of blood mononuclear cells after plasmapheresis treatment of patients with demyelinating disease. AB - Induction of lymphocytic proliferation has been postulated to be a mechanism whereby plasmapheresis may enhance the action of cytotoxic immunosuppressive drugs. This study found increased spontaneous proliferation of peripheral blood mononuclear cells following intensive plasmapheresis treatment of patients with multiple sclerosis (MS) or Guillain-Barre syndrome (GBS). The increased proliferative response was reduced below baseline in four of six MS patients who received subsequent immunoglobulin intravenous (IGIV) and pulsed cyclophosphamide therapy, but not in three MS patients receiving IGIV alone. In five GBS patients with low baseline proliferation, proliferation also increased after plasmapheresis. High baseline proliferation found in three GBS patients may have reflected antecedent infection, since it fell during plasmapheresis in the two patients in whom it was measured. Plasmapheresis could possibly augment the effectiveness of cytotoxic drugs in controlling autoimmunity by inducing lymphocytes to proliferate, thereby making them more susceptible to drug action. PMID- 2229404 TI - Immunoglobulin binding to neuronal cell surface epitopes in murine systemic lupus erythematosus. AB - Screening serum by enzyme-linked immunosorbent assay (ELISA) to paraformaldehyde fixed neuroblastoma cells revealed spontaneous neuron-reactive antibodies in three strains of autoimmune mice not present in comparable studies of BALB/c mice. Immunoglobulin isolation from pooled sera by either ammonium sulfate precipitation or passage over a protein G column enabled quantitative binding by (1) ELISA to neuroblastoma cells and (2) Western blots of plasma membrane preparations of brain cortex and neuroblastoma cells. The antibodies recognized proteins of apparent molecular weights 101,000, 68,000, 63,000, 57,000, 53,000, 43,000, 39,000, and 31,000 Da on the brain cortex and 63,000, 57,000, and 43,000 Da on the neuroblastoma cell membranes. The class of antibody binding was predominantly IgG in the MRL/lpr and IgM in the NZB/W. Differences between MRL/lpr, NZB/W and BXSB mice were observed although it is not yet apparent if this represents a difference in autoantibody production between the strains. PMID- 2229405 TI - Effects of colony stimulating factors on isolated microglia in vitro. AB - Effects of colony stimulating factors (CSF), known regulators for cells in monocytic lineage, on isolated microglia were examined. Interleukin-3 (IL-3) induced only morphological changes in rod-shaped microglia, while granulocyte macrophage CSF (GM-CSF) and CSF-1 induced both morphological changes and proliferation of microglia. CSF-1 also activated the enzyme activity of microglia. These observations indicated that, in terms of regulation by cytokines, microglia are similar to mature cells in monocytic lineage. Although astrocytes reportedly produce IL-3 and GM-CSF, the effects of astrocyte conditioned medium (Ast-Sup) were different from those of either IL-3 or GM-CSF. Ast-Sup caused ameboid microglia to become ramified, and did not induce proliferation of microglia. Factors from astrocytes may have a role in the transformation of microglia which occurs in either normal developing brain or inflammation in the brain. PMID- 2229406 TI - Discontinuous distribution of IgG oligoclonal bands in cerebrospinal fluid from multiple sclerosis patients. AB - To test the effect of sampling on the detection of immunoglobulin (Ig) cerebrospinal fluid (CSF) abnormalities, we analyzed the first and last 1 ml fraction of 10 ml obtained during a single CSF removal from 27 multiple sclerosis (MS) patients and six patients with other neurological diseases. IgG index, hyperbolic function, and IgG synthesis rate decreased between the first and the last CSF aliquot. Discordant results were found in 4/27 (15%) MS patients. In 2/27 (7.5%) clinically definite MS patients, the number of CSF oligoclonal bands (OCB) decreased between the first and the last fraction. In one of the two patients, the three OCB visualized in the first fraction were not found in the last. We conclude that fractionated sampling may partially account for the absence of OCB in the CSF of some definite MS patients. PMID- 2229407 TI - Astrocyte-conditioned medium stimulates HIV-1 expression in a chronically infected promonocyte clone. AB - Human promonocytic cells chronically infected with human immunodeficiency virus-1 (HIV-1) (clone U1.1.5) were grown in the presence of media conditioned by primary rat cortical astrocytes and HIV-1 expression was assessed by measuring reverse transcriptase activity. Media conditioned by non-stimulated and lipopolysaccharide (LPS)-stimulated astrocytes induced the expression of HIV-1 2.1-fold and 4.1-fold, respectively. LPS alone, media conditioned by the uninfected parental cell line of U1.1.5 (U937), and culture media from four other cell lines, had no effect on viral expression. The magnitude of induction was time- and dose-dependent. Tumor necrosis factor alpha (TNF-alpha) was detected in LPS-stimulated astrocyte-conditioned medium and the HIV-inducing capability of the medium was neutralized, in part, by an antibody to recombinant murine TNF alpha. These results suggest a role for astrocytes in the induction of HIV expression and thus in the pathogenesis of HIV-1 infection in brain. PMID- 2229408 TI - Identification of IgE-positive cells and mast cells in frozen sections of multiple sclerosis brains. AB - There is evidence that nervous system mast cells may be involved in the pathogenesis of experimental demyelinating diseases, and that their involvement may be mediated by IgE. In order to examine the possible relevance of these observations to human demyelinating diseases, we have histologically and immunocytochemically examined multiple sclerosis (MS) and control brains for the presence of mast cells and IgE. Using a highly specific antiserum, we found IgE positive cells in MS brains, but not in controls. IgE-positive cells could be detected in all regions of MS lesions, but were far more frequent in areas of active infiltration. Immunopositive staining was only observed when sections were pretreated with a methanolic peroxide solution, suggesting that the IgE was cytoplasmic. Positive cells typically exhibited plasma cell morphology. Mast cells were identified using chloroacetate esterase (CAE) staining, and we were able to confirm previous reports of an increased association of mast cells with MS lesions. Mast cells were seen in 7/14 MS brains compared with 1/8 controls. They were most commonly observed in demyelinated areas, but were also seen in association with infiltrate. Mast cells and IgE-positive cells were also observed in areas of perivascular infiltration in other inflammatory central nervous system diseases (subacute sclerosing panencephalitis, herpes encephalitis). Mast cells may represent a route for infiltrating cells to enter the brain in inflammatory disorders. PMID- 2229409 TI - Elevation of tumor necrosis factor in head injury. AB - Tumor necrosis factor (TNF) is a cytokine which mediates protein wasting in pathological states by promoting the catabolism of visceral tissues and skeletal muscle. The role that TNF plays in nitrogen wasting following head injury was studied by measuring TNF in the serum of 21 patients with severe head injury. Parallel measurements of TNF and urinary nitrogen excretion were performed on days 1, 3, and 5 after head injury. TNF values after head injury ranged from 65 pg/ml to 7500 pg/ml, with a mean of 1147 pg/ml, compared to control values of serum TNF of less than 38 pg/ml. The mean daily urinary nitrogen loss was 13 g/day with a range of 2.8 to 27.6 g/day, and the mean nitrogen balance was -5.8 g with a range of +4.6 to -19.1 g. While both serum TNF levels and nitrogen loss were increased after head injury, the elevation of TNF did not correlate strongly with nitrogen wasting. PMID- 2229410 TI - Brain specific autoantibodies in murine models of systemic lupus erythematosus. AB - Autoantibodies which bind to integral membrane proteins of brain were tested for their ability to bind to cross-reactive antigens on non-neural tissue. Both brain specific autoantibodies and antibodies which bind to cross-reactive antigens were found. There were two types of brain reactive autoantibodies which could not be adsorbed by non-neural tissue. One type was adsorbable by crude cell membrane preparations of brain. The second type was reactive against integral membrane proteins of brain, but not adsorbable by any of the crude membrane preparations tested. Autoantibodies of the first type reacted against integral membrane proteins with apparent molecular weights of 75, 70, 62, 50, 27, 24 and 20 kDa, as determined by gel electrophoresis and immunoblotting. As in previous studies, a diversity of brain reactive autoantibodies were found. The greatest numbers and strongest banding patterns were seen in the autoimmune strains of mice. The non autoimmune strain displayed these autoantibodies at much lower levels. These results are the first to find brain specific autoantibodies, from autoimmune mice, against integral brain membrane antigens. The data support the idea that there is a sub-population of brain reactive autoantibodies which are involved in the pathogenesis of neuropsychiatric manifestations in immunologic disorders, particularly systemic lupus erythematosus. PMID- 2229411 TI - Human astrocytes proliferate in response to tumor necrosis factor alpha. AB - Two different human astrocytic cell lines derived from adult epilepsy surgical specimens were exposed in vitro to concentrations of 1-100 ng/ml recombinant tumor necrosis factor alpha (TNF alpha). Results indicated dose-dependent stimulation of DNA synthesis and proliferation. Both of these effects were abrogated by treatment with monoclonal antibody specific for TNF alpha but not by irrelevant murine IgG. Immunocytochemical characterization of TNF alpha-treated and control cultures indicated that greater than 98% of proliferating cells contained cytoplasmic glial fibrillary acidic protein (GFAP), and were therefore astrocytic in nature. These studies demonstrate that growth of adult human non neoplastic astrocytes is stimulated by TNF alpha, an inflammatory cytokine produced primarily by macrophages but also by astrocytes. PMID- 2229412 TI - The health impact of "low intensity conflict". PMID- 2229413 TI - The future of public health: a survey of the states. AB - A survey of state health agencies was conducted to determine agreement and disagreement of state health officers with the recommendations contained in The Future of Public Health issued by the Institute of Medicine in 1988. The survey also measured the extent to which the IOM recommendations were judged currently in place or in the process of being implemented in the states. The survey showed almost unanimous consensus among the nation's state health officers for the vast majority of the recommendations. There was less consensus concerning the appropriateness of locating substance abuse, Medicaid, mental health, and regulation of health professions within state departments of health. However, a significant proportion of health officers favored a health agency location for these responsibilities (72%, 52%, 48%, and 38% respectively). PMID- 2229414 TI - A separate department of health in Washington State: four years before the mast. AB - This paper reviews the recent experience in Washington State which resulted in creation of a separate state Department of Health. Until the 1989 legislation was passed, Washington was one of 19 states in which public health was organizationally housed in a superagency. The Institute of Medicine, in its 1988 report on The Future of Public Health, recommended that states organize core functions under a separate department of health. The effort in Washington State was led by local public health officials. Success followed four years of hard work during which mistakes were made, coalitions were built, and legislative process was learned. PMID- 2229415 TI - Non-participative policy development: the genesis of A New Perspective on the Health of Canadians. PMID- 2229416 TI - Citizen participation in rural health: a promising resource. AB - The role of consumers in rural health care is explored in this review of the literature. A brief history of public, private, and grassroots efforts to involve consumers in health care is presented. A more in-depth analysis of two primary areas where consumers can be useful resources for addressing rural health care problems--personnel shortages and improving community acceptance of health care innovations--is discussed. Emergency medical services, care for medically disabled persons, and prenatal care are specifically addressed. Barriers to effective citizen participation and policy recommendations are also presented. PMID- 2229417 TI - Risk communication about environmental hazards. AB - The development of the new field of risk communication of environmental hazards is briefly described and the term "risk communication" is defined. This is followed by a description of the eight basic steps in risk communication about environmental hazards including: 1) assessing the risk; 2) setting goals; 3) assessing the target audiences; 4) assessing the socio-cultural context; 5) choosing the approach; 6) constructing the communications; 7) implementing the risk program; and 8) evaluating the effects. In describing each step, relevant literature concerning risk communication is reviewed. PMID- 2229418 TI - Karl Evang: a giant in public health. AB - Karl Evang (1902-1981) was one of the leading figures in public health in the post-World War II era. His first contributions were in social epidemiology in the 1920s-30s, and his studies on sexually transmitted diseases, nutrition and health, and occupation and health, were seminal. He was instrumental in framing the constitutions of two key U.N. agencies, the Food and Agricultural Organization and the World Health Organization, and he helped shape the WHO definition of health. Following the war, as Norway's Director General of Health, he helped create one of the preeminent humanitarian democracies and its welfare state. He and his generation of public health workers were so effective because of ties to the dominant labor parties, the need for government intervention as a result of the Great Depression and the Second World War, and the humanistic reaction to the Nazi horrors. At the same time, their excessive emphasis on medical care, and the role of the physician in health policy, resulted in the great medical costs of today. Those who believe in activist government and the goal of equality in health status owe an enormous debt to Evang and his generation. PMID- 2229419 TI - Testimony on alcohol advertising. U.S. House of Representatives Subcommittee on Transportation and Hazardous Materials, March 1, 1990. PMID- 2229421 TI - Direct enzyme-linked immunosorbent assay of anti-peptide antibodies using capture of biotinylated peptides by immobilized avidin. AB - Synthetic peptides were prepared by a solid-phase method and biotinylated selectively and in high yield at the amino terminus prior to peptide deprotection and detachment from synthesis resin. It was shown that peptides biotinylated in this manner could be bound by avidin immobilized on a plastic surface and used to detect anti-peptide antibodies in an enzyme-linked immunosorbent assay. The advantages of this method compared to conventional immunoassay techniques for anti-peptide antibodies are discussed. PMID- 2229420 TI - Validation in rat plasma of a direct radioimmunoassay for a luteinizing hormone releasing hormone antagonist (BIM 21009) AB - Rabbits were immunized with [Ac-D-beta-Nal1-, D-p-Cl-Phe2, D-Phe3, D-Arg6, Phe7, D-Ala10]LHRH (BIM 21009) coupled to bovine serum albumin using bis-diazotized benzidine. The best antiserum had an affinity of 5. 10(-10) M and a specificity directed against the C-terminal part of the molecule. The antiserum was not affected by native LHRH but reacted to some extent with detergents. Assay of free peptide plasma after gel filtration on Ultrogel AcA 34 showed apparent immunoreactivity associated with albumin and lipoproteins. The sensitivity of direct assay was 0.4 ng/ml. Measurements of BIM 21009 after s.c. injection in rats showed the resistance of the peptide to elimination. The specificity of the determinations in plasma were checked by High Performance Liquid Chromatography. PMID- 2229422 TI - Radioimmunoassay for albuterol using a monoclonal antibody: application for direct quantification in horse urine. AB - A monoclonal antibody was synthesized in mouse against the O-(3-carboxypropionyl) derivative of albuterol linked to bovine serum albumin. Isotyping of this material revealed the IgG1 class characterized by an affinity constant of 1.03 nM 1 and a density of sites of 0.55 nM. This antibody was found specific as its cross-reactivity to structurally related molecules was less than 1% except for clenbuterol (75%). A radioimmunoassay was set up with culture supernatant (final dilution 1/1000) and [3H] albuterol. The calibration curve was characterized by a maximum binding of 28%, an ED50 of 1.15 pmol per tube, the detection limit was 28.8 fmol/tube and the linearity of the response was up to 39.8 pmol/tube. This RIA method has been used for direct quantitation of albuterol in horse urine without any clean-up or extraction step. PMID- 2229423 TI - Enzyme immunoassay for pigeon breeders' disease without the use of extraneous antibody. AB - A rapid enzyme immunoassay technique is described for the detection in human sera of antibodies of any class to pigeon antigens. The method is based on binding human antibodies in excess to polystyrene-fixed antigens from pigeon droppings or pigeon serum, followed by capture of the same antigens coupled to peroxidase. A very good correlation was found of titers obtained by means of this 60-min assay with traditional sandwich immunoassay and with precipitation- and complement - fixation tests. PMID- 2229424 TI - A radioimmunoassay of bile acids. AB - A radioimmunoassay for beta-muricholic acid was developed using an antiserum which was prepared by injecting beta-muricholic acid conjugated with bovine serum albumin into rabbits. The antiserum reacted with glyco-beta-muricholic, tauro beta-muricholic and beta-muricholic acids, but not with other bile acids. The radioimmunoassay showed good reproducibility with inter- and intra-assay coefficients of variations of 6% to 15%. When the validity of the method was examined by comparing it with a gas-liquid chromatography method, a linear correlation was obtained. PMID- 2229425 TI - Simultaneous immunoenzymometric assay for antibodies against human interleukin-2 and human serum albumin in rat serum. AB - A simultaneous immunoenzymometric assay for anti-human interleukin-2 antibody and anti-human serum albumin antibody in rat serum was developed. Two antigen immobilized polystyrene balls were immersed in a diluted serum sample in an assay tube and then the antibodies on the balls were made to react with a horseradish peroxidase labelled anti-rat IgG antibody in the same tube after washing. The enzyme activity of each ball was measured by fluorometry. Not only were the sensitivity (70 ng/ml each), assay recovery (100-101%), and precision (C.V. = 5 13%) comparable to those of conventional immunoenzymometric assays using one antigen-immobilized ball but the assay was also much more feasible for mass routine assays. Thus, conventional immunoassays can be replaced by this convenient simultaneous method. PMID- 2229426 TI - ACP Broadsheet No 126: October 1990. Examination of specimens of the larynx. PMID- 2229427 TI - Pathology across Europe: differences and similarities. 3. Histopathology. PMID- 2229428 TI - Application of 1 nm gold probes on paraffin wax sections for in situ hybridisation histochemistry. AB - An in situ hybridisation technique that uses 1 nm immunogold reagents and silver enhancement was devised to detect biotinylated DNA viral probes in formalin fixed, paraffin wax sections of human cervix. DNA probes labelled with biotin-11 deoxyuridine triphosphate were detected after hybridisation to nucleic acid sequences by an antibiotin antibody, followed by a gold labelled secondary antibody. Silver enhancement then permitted visualisation of the signal at the light microscopic level. The method was reliable and produced less background staining than previously described methods. The signal could be enhanced by epi polarisation microscopy. Furthermore, biotinylated DNA probes may be detected directly by a 1 nm gold labelled goat antibiotin antibody without loss of labelling intensity, and this may be preferable to the longer two layer technique, previously described. PMID- 2229429 TI - Use of immunoelectron microscopy to show Ebola virus during the 1989 United States epizootic. AB - A filovirus, serologically related to Ebola virus, was detected by "post embedment" immunoelectron microscopical examination of MA-104 cells. These had been infected by inoculation with serum samples obtained during the 1989 epizootic in cynomolgus monkeys (Macaca fascicularis), imported from the Philippines and maintained at Reston, Virginia, USA, a primate holding facility. The immunoelectron microscopy method, when used in conjunction with standard transmission electron microscopy (TEM) of infected cells, provided consistent results and was simple to perform in this epizootic. It is concluded that immunoelectron microscopy is potentially useful in the direct immunological diagnosis of Ebola and related filoviral infections (such as Marburg) in clinical samples obtained from those with acute infection. PMID- 2229430 TI - Adenomyosis in Pakistani women: four year experience at the Aga Khan University Medical Centre, Karachi. AB - As part of a quality assurance programme at the Aga Khan University Medical Centre, Karachi, Pakistan, all hysterectomy specimens were reviewed from January 1986 to December 1989. Adenomyosis was found in 237 of the 419 (56.5%) specimens studied. Of these 237 patients, 232 (97.9%) were parous and 196 (82.8%) were in the fourth and fifth decades of life. This high prevalence in parous women aged 40-59 years was significant. Fibroids, cervicitis, and endometrial hyperplasia were the most common associated diagnoses. Of all the associations studied, only endometrial hyperplasia was significantly more prevalent in the group with adenomyosis. Adenomyosis was stated as an indication for surgery in 69 patients and was confirmed by histopathology in 49 (71%). Preoperative suspicion of adenomyosis was present in 49 (20.6%) patients of all those ultimately found to have the disease. There is a high prevalence of adenomyosis in the population studied, which indicates that the condition may have been underdiagnosed in the past, especially as it is difficult to diagnose without surgery and hysterectomy is currently the only treatment. PMID- 2229432 TI - Computer assisted selection and assessment of antibodies in the diagnosis of lymphomas. AB - With increasing numbers of reagents the problem of selecting appropriate antibodies to solve problems in the diagnosis of lymphoma is becoming more complex. One approach is to use a computer program to optimise the selection process. Such a program was devised, incorporating data from an extensive literature search. When presented with a differential diagnosis it selects the most appropriate antibody panel and when given the results evaluates the relative likelihood of each possible diagnosis. In a retrospective study 81% of the tests used had been non-discriminatory, but using the results of the remaining 19% of the tests, the computer was able to select the "correct" diagnosis with a high degree of certainty. The development and use of this system illustrated several problems in the application of computer assisted diagnostic techniques in histopathology. These problems include incomplete data and lack of understanding of the process of histopathological diagnosis. PMID- 2229431 TI - Tissue preparation for simultaneous flow cytometric quantitation of tumour associated antigens and DNA in solid tumours. AB - A multiparameter flow cytometric assay for the simultaneous study of tumour associated antigens (TAA) and DNA in fresh solid tumours was devised. Cell suspensions were prepared by disaggregating unfixed solid tumour samples mechanically over a stainless steel mesh. Indirect immunofluorescence was used to identify the TAA, and DNA was stained with propidium iodide. Cell morphology was well preserved, cell clumping was negligible, and high quality indirect immunofluorescence quality indirect immunofluorescence and DNA staining were obtained. The technique is simple, rapid, and reproducible. Multiparameter assays can be developed to study prognostic indicators such as membrane oncoproteins, receptors, and multidrug resistance in solid tumours. With a suitable panel of antibodies the technique might become an aid in the differential diagnosis and biochemical diagnosis of some solid tumours. PMID- 2229433 TI - Immunocytochemical analysis of lymph node aspirates in patients with human immunodeficiency virus infection. AB - Thirty four patients positive for human immunodeficiency virus (HIV) who had lymphadenopathy were investigated using fine needle aspiration. Cytological analysis included immunocytochemical investigation with the alkaline phosphatase antialkaline phosphatase (APAAP) method. All patients had confirmation of cytological diagnosis by lymph node biopsy. Fifteen aspirates with follicular hyperplasia were evaluated. Eleven patients showed B cell predominance. The B cell population did not show light chain restriction. Ten patients with B cell non-Hodgkin's lymphoma (five with Burkitt's lymphoma and five with B cell immunoblastic lymphoma) were investigated. Nine out of 10 cases were monoclonal with respect to their light chain determinants; only one case with Burkitt's lymphoma with partial lymph node metastasis did not show light chain restriction. The cytological diagnosis included two mycobacterial infections and four cystic lesions. Histological investigation was necessary to diagnose the extent of lymph node disease caused by Kaposi's sarcoma. These findings indicate that the immunocytological investigation of lymph node aspirates is useful for evaluating lymphadenopathy in HIV positive patients. PMID- 2229435 TI - Use of latex agglutination technique for detecting Legionella pneumophila (serogroup 1) antibodies. AB - Following the outbreak of Legionnaires' disease in Stafford in 1985, 500 serum samples were submitted to the indirect immunofluorescence antibody test and a latex agglutination. Latex agglutination using ultrasonically disrupted Legionella pneumophila antigens coupled to latex particles, proved a rapid, simple method for detecting circulating antibodies to L pneumophila in a one minute slide latex agglutination test. There was good correlation with the indirect immunofluorescence antibody test (IFAT), and the specificity and sensitivity with respect to a diagnostic result were 98.3% and 97.6%, respectively, using a series of well characterised sera. The latex agglutination test seems well suited as a screening test for presumptive cases of Legionnaires' disease; the latex reagent is easy to prepare and seems to remain stable at 4 degrees C for up to six months. PMID- 2229434 TI - Observations on the haemopoietic response to critical illness. AB - Peripheral blood cytopenias are common in patients receiving intensive care, particularly in those with multiple organ failure. To assess the contribution of bone marrow hypoplasia in such patients 44 bone marrow samples from 24 patients under intensive care were studied by standard morphological techniques and by the granulocyte-macrophage colony forming cell (GM-CFC) assay. Frequently observed morphological abnormalities in the bone marrow included the following: (i) a reduction in overall cellularity in seven patients, with a progressive decrease in most patients studied sequentially; (ii) an increase in the number of actively phagocytic macrophages; and (iii) a disruption of normal bone marrow architecture with the accumulation of intercellular hyaluronic acid glycosaminoglycan. Mean GM CFC growth was significantly reduced when compared with that in a group of normal controls. In four of five patients studied sequentially GM-CFC growth became subnormal in association with a reduction in bone marrow cellularity. Inhibitory serum factors were not identified. These morphological abnormalities are similar to the changes observed in gelatinous degeneration of the bone marrow. In both situations disruption of the haemopoietic microenvironment, with the accumulation of hyaluronic acid proteoglycan, may be an important factor in the inhibition of haemopoietic progenitor cell growth. The proliferation of macrophages, by the release of a variety of cytokines or reactive oxygen intermediates, may also be implicated in impaired haemopoiesis and the development of disordered erythropoiesis. PMID- 2229436 TI - Comparison of methods for the diagnosis of typhoid fever. AB - Over five years the Bactec radiometric blood culture method yielded Salmonella typhi in 41 of 45 confirmed cases of typhoid fever, 90% of which were from the first culture set taken. Blood clot culture was positive in 18 (41%) of 44 confirmed cases and stool culture in 24 (59%) of 41. The yield from 2189 Widal clot cultures was only 0.03%. There were 68 positive results in 2258 unpaired Widal tests: 23 of them were falsely positive and 13 falsely negative, but in 11 out of 68 cases the Widal was the only positive laboratory test. It is concluded that routine clot culture is not cost effective if a sensitive blood culture method is used, and that the Widal test is useful only in selected patients. PMID- 2229437 TI - Production of extra-cellular slime by Staphylococcus epidermidis during stationary phase of growth: its association with adherence to implantable devices. AB - A method of optimising slime production produced by Staphylococcus epidermis and its quantitative assay was developed, which gave a preliminary indication of its identity and an assessment of the correlation between slime production and adherence of the organism to implants. After inducing vigorous growth in brain heart infusion broth to stationary phase, all nutrients were removed by washing and the organisms resuspended in sterile deionised water with added magnesium. After further incubation the culture was centrifuged and the supernatant reacted with alcian blue in 50 mM magnesium chloride/sodium acetate solution, and the amount of bound dye was measured spectrophotometrically at 620 nm after its resolubilisation using sodium dodecyl sulphate. Large quantities of slime were produced by some, but not all, strains. Preliminary electrophoresis of the slime showed mobility and staining similar to that of the glycosaminoglycans. Adherence was tested by growing strains in wells of tissue culture plates and aspirating the supernatant after incubation. After fixation and staining of adherent growth the amount of bound stain was determined spectrophotometrically after its elution with ethanol. In this series of organisms there was no correlation between the result of tests for adherence or production of extracellular slime, and no correlation between either of these and the clinical source of the organisms. PMID- 2229438 TI - Immunoblot technique to visualise serum pepsinogen A isozymogen patterns. AB - Pepsinogen A (PGA) isozymogen patterns in urine and gastric mucosa can be visualised in non-denatured polyacrylamide gel electrophoresis by showing proteolytic activity after the conversion of pepsinogen into pepsin by acid. This method is not suitable for visualising PGA patterns in serum due to low PGA concentrations. To obtain a more sensitive visualisation method an immunoblotting technique was developed. PGA isozymogen patterns from urine and sonified gastric mucosa specimens obtained by immunoblotting were identical with those obtained by activity staining. The immunostaining method was at least 50 times more sensitive. PGA isozymogen patterns could be visualised in serum. Preliminary results suggest that the PGA patterns in serum and gastric mucosa are identical. As an association has been found between the genetically determined PGA isozymogen patterns in gastric mucosa and gastric malignancies in man, immunoblotting of PGA isozymogens in serum may provide a screening tool for subjects at risk of malignant gastric disease. PMID- 2229439 TI - Rapid identification of Klebsiella. PMID- 2229440 TI - Screening of urines with dipstrips: does it reduce workload and consumable costs? PMID- 2229441 TI - Successful treatment of chronic immune thrombocytopenia using fresh frozen plasma. PMID- 2229442 TI - Leukaemic phase of mantle zone lymphoma. PMID- 2229443 TI - Hypercalcemia and osteolytic lesions associated with chronic lymphatic leukemia (CLL) PMID- 2229444 TI - Thoracic aortitis due to Salmonella. PMID- 2229445 TI - Risk of metastasis during fine needle aspiration. PMID- 2229446 TI - The regulatory status of radiopharmaceuticals in Europe. PMID- 2229447 TI - Drug delivery systems. 4. Implants in drug delivery. AB - In comparison with many of the other drug delivery systems, implantable pumps and implants for variable rate delivery are at a crude stage of development. Although exceptions exist, the typical implantable pump consists of an electromechanically complex mechanism to regulate drug delivery from a percutaneous refillable reservoir, while power to drive the system comes from a transcutaneous energy transmission system. The potential for electrical or mechanical failure is high, and the systems are not yet sufficiently convenient or easy to use to recommend in a routine therapy. Problems with refilling of an apparently well designed implanted reservoir have been observed while, at the same time, cutaneous energy transmission systems are not well established. In most instances, the development of an elementary osmotic pump system dosage form follows a well defined path of physical-chemical formulation and clinical testing. The benefits most often provided by the dosage form are expected to be (1) increase in selectivity of drug action achieved by the system's zero-order release rate, and (2) decrease in frequency of administration. The success in achieving these values is quantifiable from the pharmacology of the drug substance and its pharmacokinetics. Osmotic and other technical approaches to producing economical, rate-controlled dosage forms will make it possible for all new pharmaecutical products to carry kinetic specification of rate as well as static specification of content. This review considers the characteristics of the ideal implantable pump, the clinical situations which require pumps, the limitations of portable pumps, and the detailed characteristics of existing implantable pumps and implants. Most of the review, however, focuses on insulin delivery because of the importance of this subject. PMID- 2229448 TI - Globalization of the pharmaceutical industry: opportunities for physicians in clinical research. PMID- 2229449 TI - Pharmacokinetics of cephradine administered intravenously and orally to young and elderly subjects. AB - The pharmacokinetics of IV and oral cephradine in healthy young male and female volunteers (ages 19 to 25, n = 10) were compared to those of older individuals (ages 65 to 81, n = 9). Subjects received 1 gram of cephradine by a 5-minute intravenous (IV) infusion followed the next day by a 1-gram oral dose. Serial serum and urine samples collected over a period of 12 hours after the dose were analyzed for cephradine concentration by a microbiologic assay. After IV administration, mean serum cephradine concentrations in the elderly group were significantly higher at both 6 hours (1.52 +/- 0.41 mcg/mL) and 8 hours (0.73 +/- 0.22 mcg/mL) than in the young group at 6 hours (0.43 +/- 0.11 mcg/mL). Total systemic clearance was significantly lower (2.64 +/- 0.34 vs. 4.81 +/- 0.59 ml/min/kg) and the elimination half-life was significantly longer (1.71 +/- 0.20 vs 1.12 +/- 0.13 hours) in the elderly group (P = .0001). Systemic cephradine clearance correlated positively with creatinine clearance (r2 = 0.34, P = .0110) and negatively with age (r2 = 0.79, P = .0052). The mean volume of distribution was not significantly different between the two groups. Mean renal clearance was significantly lower in the elderly group (P = .0001), but more than 80% of the dose was excreted in the urine within 6 hours in both groups. After oral administration, the mean peak concentration and time to peak concentration did not differ between groups. The relative oral bioavailability was approximately 94% in both groups. The mean serum concentrations in the elderly were higher at both 6 and 8 hours than in the young group at 6 hours. There were no differences in pharmacokinetic parameters between male and female subjects. Because of reduced cephradine clearance secondary to an age-related decline in renal function, administration of cephradine every 8 hours, rather than every 6 hours, may be sufficient in elderly patients. PMID- 2229450 TI - Safety, tolerance, and pharmacokinetics of cefepime administered intramuscularly to healthy subjects. AB - Steady state pharmacokinetics, absolute bioavailability, and dose proportionality of cefepime were evaluated in healthy male subjects after single (250, 500, 1000, or 2000 mg) and multiple (1000 mg every 12 hours for 10 days) intramuscular injections. Safety and tolerance were also monitored. High performance liquid chromatography/UV methodology was used to determine cefepime concentrations in plasma and urine. Key pharmacokinetic parameters were determined using noncompartmental methods. Cefepime was absorbed rapidly; mean peak times were 1.0 1.6 hours. Pharmacokinetics were linear over the 250-mg to 2000-mg dose range, with mean total body clearance ranging from 125 to 141 mL/min. The peak plasma concentration and area under the curve increased in a dose-proportional manner. The apparent elimination half-life (2 hours) did not appear to be influenced by dose or by duration of dosing. No accumulation of cefepime was observed during the multiple-dose study. More than 80% of the administered dose was excreted in the urine as unchanged cefepime, and absolute bioavailability after intramuscular dose was 100%. Cefepime was well tolerated. Most subjects experienced none to mild pain and only minimum discomfort at the site of injection. PMID- 2229451 TI - The effect of ciprofloxacin on the pharmacokinetic and ECG parameters of quinidine. AB - Ciprofloxacin decreases the clearance of antipyrine and other drugs which, in part, undergo oxidative metabolism. Based on these findings, the authors hypothesized that ciprofloxacin may decrease the clearance of quinidine, a drug which also undergoes oxidative metabolism. The purpose of this study was to evaluate the effect of ciprofloxacin on the pharmacokinetic and ECG parameters of quinidine in seven healthy men. Oral quinidine sulfate 400 mg was administered alone (Phase A) and after oral ciprofloxacin pretreatment (Phase B) in a randomized crossover fashion with a 2-week washout period between each phase. During Phase B, ciprofloxacin pretreatment (750 mg every 12 hours) was administered for 5 days before and 24 hours after quinidine administration. Quinidine serum samples were obtained over a 24-hour period. QRS and QTc intervals were measured over a 12-hour period. There were no significant differences in clearance (20.3 +/- 3.3 L/hr vs 20.1 +/- 2.3 L/hr, P = .836), half life (7.9 +/- 1 hr vs 7.8 +/- 0.8 hr, P = 0.8), maximum concentration (1.4 +/- 0.6 mg/L vs 1.5 +/- 0.6 mg/L, P = 0.613), or time to maximum concentration (1.5 +/- 0.2 hr vs 1.5 +/- 0.1 hr, P = 0.571) for quinidine between Phase A and Phase B, respectively. The largest decrease in clearance observed for Phase B compared to Phase A was 10%. There was also no significant difference in the degree of QRS and QTc prolongation between Phase A and Phase B. From these results, it appears that ciprofloxacin in the dose given does not alter the pharmacokinetic or ECG parameters of quinidine. Therefore, no adjustment in the dose of quinidine is needed when coadministered with ciprofloxacin. PMID- 2229452 TI - The long-term treatment of stable angina pectoris with verapamil. AB - In a double-blind 16-week crossover study, the effectiveness of verapamil therapy for chronic stable angina was evaluated in 19 patients (Phase I). Twelve of these patients were then followed for 38 to 58 months of open-label treatment (Phase II). Clinical responses were assessed with traditional indices, treadmill exercise tests, and a newly developed Performance Index (PI). During Phase I, verapamil resulted in a 50% mean reduction in the number of patients developing effort angina on treadmill exercise, a 15% mean increase in treadmill exercise time, and an 18% mean improvement in the PI. In eight of ten patients, diastolic blood pressure rises during exercise were significantly lowered during verapamil treatment in Phase I. In a limited population of patients followed for long periods of time, our data show that verapamil remains acceptably effective in the treatment of angina pectoris. Though diastolic blood pressure rises were decreased during Phase I, we could not confirm that effect over longer periods of time. Functional capacity as determined by the PI was sustained in Phase II. PMID- 2229453 TI - Estimation of hepatic blood flow in branches of hepatic vessels utilizing a noninvasive, duplex Doppler method. AB - The measurement of hepatic blood flow by indirect methods such as indocyanine green clearance has several limitations. The duplex Doppler offers the potential for noninvasive, real-time measurement of blood flow and has been employed in the evaluation of arterial disease in a variety of vascular beds. We evaluated Doppler ultrasound estimation of blood flow in branches of the hepatic artery, hepatic vein, and portal vein in 12 healthy subjects on two separate days. In vitro accuracy of the scanner was assessed using phantom targets of known diameter and velocity. Blood velocity and vessel diameter measurements were obtained five times over a period of 2 hours. No significant differences were seen in velocity or blood flow measurements within or between days. The interday coefficients of variation, which include intrasubject variability, were 10-15% and 14-20% for velocity and blood flow measurements, respectively. This study demonstrates the potential utility of Doppler ultrasound to detect intrinsic, drug, or disease-induced changes in hepatic blood flow. PMID- 2229454 TI - Pharmacokinetics of quinapril and its active metabolite, quinaprilat, in patients on chronic hemodialysis. AB - The pharmacokinetics of quinapril and its active metabolite, quinaprilat, were evaluated in 12 patients with end-stage renal disease (ESRD) on chronic hemodialysis. Each subject received a single 20-mg oral dose of quinapril 4 hours before a 4-hour hemodialysis treatment. Serial dialysate and blood samples were obtained over 4 and 96 hours, respectively. Samples were analyzed for quinapril and quinaprilat concentrations by gas chromatography. Mean tmax and Cmax values for quinapril were 1.2 hours and 129 ng/mL, respectively. Only one patient had detectable quinapril dialysate concentrations which accounted for 2.8% of the quinapril dose. Mean apparent plasma clearance for quinapril was 1275 mL/min with a mean half-life of 1.7 hours. Quinapril was extensively de-esterified to its diacid metabolite, quinaprilat. Mean tmax and Cmax for quinaprilat were 4.5 hours and 671 ng/mL, respectively. Mean apparent plasma clearance for quinaprilat was 24.0 mL/min with a mean half-life of 17.5 hours. As with quinapril, quinaprilat was not readily dialyzable. Only 5.4% of the administered quinapril dose was recovered as quinaprilat during a single hemodialysis treatment. In view of these results, supplemental quinapril doses need not be routinely given to patients following hemodialysis. Overall, quinapril and quinaprilat pharmacokinetics in patients with ESRD on chronic hemodialysis were not markedly different from those previously observed in patients with moderate to severe renal dysfunction (CLcr less than 29 mL/min) not yet requiring hemodialysis (RDND). PMID- 2229455 TI - Multiple dose pharmacokinetics, safety, and tolerance of velnacrine (HP 029) in healthy elderly subjects: a potential therapeutic agent for Alzheimer's disease. AB - The pharmacokinetics, safety, and tolerance of 1,2,3,4-tetrahydro-9-aminoacridin 1-olmaleate (HP 029) a potential therapeutic agent for Alzheimer's disease, were assessed after multiple oral doses in a randomized double-blind, placebo controlled, ascending dose study in 56 healthy elderly men (14 per dose group). The subjects in the first three groups received 25, 50, or 100 mg two times a day and a fourth group was administered 100 mg velnacrine tid for 28 days. All subjects received a final dose on day 29. Subjects were confined for continuous observation during the 36-day study period. Blood and urine samples were collected for the pharmacokinetic assessment. There were no clinically important changes in the safety variables in both age groups after any dose. There was no evidence of hepatotoxicity when elderly men were given 100 mg tid for 28 days. Nine subjects reported one or two episodes of gastrointestinal (diarrhea) side effects (6 in the 100 mg bid group and 3 in the 100 mg tid dose group) during a 29-day trial. None required treatment or were discontinued from study. These results indicate that the safety and tolerance up to 100 mg tid for 28 days in healthy elderly men are acceptable. Velnacrine was rapidly absorbed after oral administration. There were dose-related increases in Cmax, AUCs, and amount of drug excreted in urine. During multiple dosing, the Cmax increased as a function of dose. The tmax and t1/2 were not affected by dosage nor multiple dosing. Steady state levels of velnacrine were reached between days 2 and 3 with no evidence of further accumulation of velnacrine thereafter. Approximately 11-30% of the administered dose was excreted in the urine over the course of the study. The favorable pharmacokinetic characteristics and acceptable safety and tolerance of multiple dosing oral doses of velnacrine support further testing of this compound for efficacy and safety in Alzheimer's patients. PMID- 2229456 TI - Effects of flurazepam and midazolam on sleep and next-day performance in chronic insomniacs: report of a multicenter study. PMID- 2229457 TI - Sleep, performance, and plasma levels in chronic insomniacs during 14-day use of flurazepam and midazolam: methodology. AB - Methods are described for a five-center study of flurazepam and midazolam, in which 107 patients with histories of benzodiazepine use for chronic insomnia were enrolled. Data were available for 99 of these patients. Staff and patient manuals and a behavior-based computer system were specially designed to measure and delineate clearly the study procedures and parameters. Patients were carefully followed and supported during a 20-day washout period and underwent extensive training on psychomotor performance tasks. They received placebo for 2 nights and were then randomly assigned to one of four study treatments--flurazepam 15 or 30 mg, midazolam 15 mg, or placebo--for 14 consecutive nights. All-night sleep electroencephalographic recordings were obtained on study nights--1 and 0 (placebo) and 1, 2, 7, 13, and 14 (treatment nights). Results of four computer generated psychomotor performance tasks and three cognitive tasks, plus subjective evaluations of sleep, performance, and mood, were recorded in the morning after each night spent in the sleep laboratory. Blood and urine samples were analyzed for drug concentrations in plasma and for compliance with the protocol. A pilot study, using a high (nonclinical) dose of flurazepam (45 mg), preceded the multi-center study and was designed to evaluate tests in healthy volunteers and to familiarize staff with equipment and tests. PMID- 2229458 TI - Drug performance sensitivity: a pilot study. AB - Thirty noninsomniac healthy adult men were enrolled in a multicenter pilot study to evaluate the sensitivity of psychomotor and cognitive tasks and subjective evaluation of performance and mood after treatment with flurazepam (Dalmane) 45 mg (larger than the recommended prescribing dose of 15-30 mg). This pilot study was also used to standardize testing procedures. The subjects were given either flurazepam or placebo at 72-hour intervals in a double-blind Latin square crossover design. Choice reaction time, but not simple reaction time, was drug sensitive. Divided attention and vigilance tasks were also sensitive to drug effects. Of the two cognitive tasks tested, addition was impaired by drug, but reading comprehension was not. Subjective evaluations of performance and mood states indicate that these are useful measures, but responses on the Hopkins Symptom Checklist were not influenced. PMID- 2229459 TI - Characteristics of chronic insomniacs examined in a multicenter 14-day study of flurazepam and midazolam. AB - One hundred seven chronic insomniacs (41 men, 66 women; mean age, 37.9 years) with a history of use of benzodiazepines were recruited for a multicenter study testing the relative efficacy of flurazepam 15 mg or 30 mg, midazolam 15 mg, or placebo during a 14-day treatment period. Average duration of the complaint of insomnia was 13.5 years. Most (74%) of the patients met criteria for a diagnosis of persistent psychophysiological sleep disorder for both initiating and maintaining sleep. PMID- 2229460 TI - Clinical safety of flurazepam and midazolam during 14-day use in chronic insomniacs. AB - Data from evening questionnaires, reports of side effects, laboratory findings, and all-night respiratory measurements were collected on the 99 chronic insomniacs examined in this multicenter study. These data were used to compare the clinical safety and desirability of a benzodiazepine hypnotic with a very short half-life, midazolam 15 mg, with a hypnotic with a longer half-life, flurazepam 15 and 30 mg; both compounds were compared with a placebo control. There were 2 prestudy placebo nights followed by 14 consecutive nights of treatment. Of the 107 patients accepted, 99 completed the study. No marked adverse reactions were found in any area for any group. There was no increase in sleep apneas during the treatment period for any group. Results of this study provide additional evidence of the safety of benzodiazepine hypnotics. PMID- 2229461 TI - A multicenter study of sleep, performance, and plasma levels in chronic insomniacs during 14-day use of flurazepam and midazolam: executive summary. PMID- 2229462 TI - Sleep evaluation in chronic insomniacs during 14-day use of flurazepam and midazolam. AB - This article contains the sleep results of the efficacy study of flurazepam 30 mg and 15 mg, midazolam 15 mg, and placebo in the 99 chronic insomniacs studied as part of this multicenter study. After a 20-day drug washout, all-night sleep was recorded on 2 baseline nights, on the first 2 treatment nights, on treatment night 7, and on the last 2 nights of the study (nights 13 and 14). To reduce the number of comparisons, electroencephalographic (EEG) sleep latency, EEG wake time, EEG sleep efficiency, post-sleep questionnaire (PSQ) sleep latency, and PSQ total sleep were preselected as the major sleep variables. Between-groups comparisons indicated that, when compared with the placebo control, all drugs improved sleep, but differences were statistically significant only for the first 2 nights, i.e., the early interval. Midazolam was more effective than either dose level of flurazepam on treatment night 1. Within-group analyses indicated that all drug groups showed significantly improved sleep from baseline throughout drug administration, but the placebo group did not significantly improve from baseline by either objective or subjective measures at any of the three time intervals. The sleep of patients taking flurazepam 30 mg did not differ significantly from the sleep of those receiving the 15 mg dose for any of the five major sleep variables at any interval. Objective EEG and subjective PSQ sleep variables showed significant positive correlations. PMID- 2229463 TI - Psychomotor performance in chronic insomniacs during 14-day use of flurazepam and midazolam. AB - Four skills performance (psychomotor) tasks, including simple and choice reaction time, divided attention, and vigilance, were given to 99 chronic insomniacs to determine whether the use of midazolam 15 mg, or of flurazepam 15 or 30 mg, compared with placebo would produce next-day impairment throughout a 14-day treatment period. Tests were administered during 2 baseline days and on treatment days 1 and 2 (early interval), 7 (middle interval) and 13 and 14 (late interval). Compared with placebo, performance on all four tasks was impaired by flurazepam 30 mg. The deficits associated with flurazepam 15 mg were roughly half the magnitude of those produced by flurazepam 30 mg, but these changes did not reach statistical significance for single response measures at single time intervals. Midazolam showed no consistent pattern of performance effects; however, for divided attention tracking error, there was a significant decrement. The placebo group showed flat performance curves or improved performance as a result of learning (practice effect). PMID- 2229464 TI - Cognitive performance and mood in patients with chronic insomnia during 14-day use of flurazepam and midazolam. AB - The 99 chronic insomniacs examined in the present multicenter study were given three cognitive tasks (reading comprehension, addition, and digit symbol substitution test [DSST]) as well as the Hopkins Symptom Checklist (HSCL) and the Profile of Mood States (POMS) in order to evaluate the effects of flurazepam (Dalmane) 15 and 30 mg, midazolam 15 mg, and placebo on cognitive performance and mood. Subjective evaluation of performance was also obtained. A significant person in the patient's life was also asked to evaluate the patient's mood before and during the 14-day treatment interval. After a 20-day washout, next-day performance and mood were evaluated after placebo nights -1 and 0 (baseline) and after treatment nights 1, 2 (early interval), 7 (middle interval), and 13 and 14 (late interval). Analysis of variance (ANOVA) on changes from baseline indicated no significant between-groups treatment effects for reading comprehension or any of the mood variables at any interval. Patients on flurazepam 30 mg performed less well compared with other groups even though, after completion of the tasks, this group believed that they performed as well as those on the other regimens. Performances by flurazepam 15 mg, midazolam, and placebo groups were similar. Significant others tended to rate high-dose flurazepam patients more negatively. High-dose flurazepam patients had a significant change on the DSST and addition tasks due to treatment after the first night, and change in performance remained significantly impaired for the DSST task relative to that of the other groups thereafter. PMID- 2229465 TI - Plasma concentrations of flurazepam and midazolam in chronic insomniacs during 14 day use and their relationship to therapeutic effects and next-day performance and mood. AB - Blood samples were drawn from each of 99 chronic insomniacs twice during washout (days -20 and -6) and six times during the study (mornings after study nights -1, 1, 2, 7, 13, and 14) to examine the relationship between morning-after drug plasma levels, sleep efficiency, next-day mood, and performance. Patients in the four treatment groups received either flurazepam 30 mg, flurazepam 15 mg, midazolam 15 mg, or placebo. Plasma drug concentrations of N-desalkylflurazepam and midazolam were measured by electron-capture gas chromatography. Values of midazolam during the 14-day study were at or near the sensitivity limit of the assay and were not used in the calculations. Levels of N-desalkylflurazepam increased as expected during the 14 days. Mean level for the high-dose flurazepam group was approximately twice that of the low-dose group. The main consistency in the correlations, which were found on days 13 and 14, was that the high-dose desalkylflurazepam concentrations had a negative correlation with two independent measures of sleep latency. However, otherwise there was little or no relationship between N-desalkylflurazepam levels and sleep efficiency or next-day behavior. Issues of tolerance, individual variability in baseline and response, and their contribution to the findings are discussed. PMID- 2229466 TI - A multicenter 14-day study of flurazepam and midazolam in chronic insomniacs: general discussion and conclusions. PMID- 2229467 TI - Correlates of a measure of coping in older veterans: a preliminary report. AB - Sense of Coherence (SOC) is a specific measure of perception of coping ability which is examined here in relation to demographic characteristics and measures of physical and mental health status of older veterans (N = 240). Results suggest that the SOC is strongly correlated with measures of subjective health status. It does not uniquely contribute to that dimension but does exhibit appropriate psychometric properties to encourage its use in further research. PMID- 2229468 TI - Injury among male migrant farm workers in South Carolina. AB - A record review and interview survey were carried out to determine the impact of injury on the health of male migrant workers in the Ridge area of South Carolina. Thirteen percent of the men's visits to the Rural Migrant Clinic were for injuries. A larger number, sixty percent, of men's visits to the local Emergency Room were due to injuries. Documentation of alcohol and drug use or the circumstances of the injury was more complete on the Emergency Room records than on the Clinic records. Interviews with 116 migrant workers were carried out in the camps during the summers of 1986 and 1987. Male migrant workers had similar rates of work related accidents as other hired farm workers in the United States. However, male migrant workers have more episodes of personal violence than black males living in other types of rural settings. Heavy drinking was associated with these violent episodes. Over 83 percent of the episodes of personal violence occurred in the camps after dark. It is suggested that camp conditions with poor sanitation, crowding, lack of recreational outlets, and high presence of available alcohol contributes to the high rates of injury in this group of men. PMID- 2229469 TI - Dietitians' beliefs about the importance of health promotion practices. AB - Registered dietitians throughout the state of Delaware (N = 146) were surveyed by mail to assess their beliefs about the importance of health promoting behaviors to the health of the average person. Respondents were instructed to rate each of 25 health promotion practices on a Likert scale. Results were compared with investigations of other health care providers. "Eating a balanced diet" was rated among the top five items. "Taking vitamin supplements" received the lowest mean rating. Results of the present study compared well with the beliefs of pharmacists and physicians. Ratings by other registered dietitians from an earlier study tended to be more conservative. Dietitians are supportive of health promotion and disease prevention. Their current role in health promotion activities needs further investigation. PMID- 2229470 TI - Common illnesses and self-care. AB - Self-care has become a topic of widespread interest in recent years. However, few studies of the content and methods of self-care are available to inform health education program design. The present study identified common illnesses that were reported by 258 western university students and how those illnesses were typically cared for. Illness reporting differed significantly by gender, marital status, and perceived health status. Illness treatment differed only for perceived health status. Results suggest that treatment of an illness once self diagnosed does not differ across groups but that labeling of illnesses does. The suggestion is made that educational programs may need to place greater emphasis on appropriate diagnosis of illness. PMID- 2229471 TI - Cytoarchitecture and fiber connections of the nucleus lateralis valvulae in the carp (Cyprinus carpio). AB - The cytoarchitecture and fiber connections of the nucleus lateralis valvulae of the carp (Cyprinus carpio) were studied by Nissl, Bodian, Golgi, and horseradish peroxidase methods. Chief cells composing the nucleus lateralis valvulae (NLV) are small and granular, and their axons terminate in the cerebellum. These neurons have no dendrite, and the cell body is enveloped in a single terminal of afferent fibers to the NLV. In order to observed local cell clustering, the NLV was three-dimensionally reconstructed with the aid of a computer image analysis system. Afferent sources to the NLV were the nucleus pretectalis superficialis pars magnocellularis (Northcutt and Braford, '84: Brain Res. 296:181-184), nucleus ventromedialis thalami (Ito et al., '86: J. Comp. Neurol 250:215-227), and the inferior lobe. The NLV projects to the inferior lobe and the cerebellum. In particular, the cerebellar projections were strong and topographically arranged. Some larger neurons lying just beneath the NLV, some of which were intermingled with the NLV neurons, projected to the torus longitudinalis. On the basis of the local cell clustering as well as NLV-cerebellar connections, three subdivisions of the NLV could be recognized, i.e., anterior, central, and posterior portions. The posterior portion was further subdivided into lateral and medial parts. PMID- 2229472 TI - Auditory brainstem in the mole (Mogera): nuclear configurations and the projections to the inferior colliculus. AB - Anatomical organization of the central auditory system in the mole was studied at the lower brainstem levels. The cyto-, myelo-, and chemoarchitectures were examined in Nissl, myelin, and acetylcholinesterase stained materials, and then the origins of the ascending afferents to the inferior colliculus (IC) were identified by injecting wheatgerm agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the unilateral IC and processing the tissue according to the standard retrograde tracing techniques. The results indicate that the auditory nuclei and pathways in the lower brainstem of the mole conform to the basic plan common to many other mammals. Nevertheless, several characteristic features are evidenced in the present study: (1) in the cochlear nucleus (CochN), granule cell fields are very large in both the ventral (VCN) and dorsal (DCN) nuclei; among several populations of neurons, fusiform cells in the DCN, multipolar cells in the VCN and DCN, and small spherical cells in the VCN project to the IC directly, (2) in the superior olivary complex (SOC), the medial nucleus (MSO) is well developed in comparison with that in the hedgehog, the opossum, the mouse, and the rat, although the general configuration of the SOC is similar to that in those mammals, most strikingly, the MSO projects to the IC bilaterally in the mole, and (3) the nuclei of the lateral lemniscus (NLL) show a great development and consist of three well-differentiated parts of the dorsal, intermediate, and ventral nuclei. The projections from these subnuclei to the IC conform to the basic mammalian plan. PMID- 2229473 TI - Distribution and projection pattern of motoneurons that innervate hindlimb muscles in the quail. AB - We characterized the motoneuron pool positions and projection patterns in the embryonic quail hindlimb and compared them to those in the chick to determine the degree of similarity and to form a baseline for future chimeric experiments. We find that the most similar parameters of pool position correlate with the major axonal pathway choices. First, the medial-lateral pool position, which is highly conserved among birds and mammals, is identical in the quail and chick and correlates with the dorsal-ventral pathway choice, the first and least plastic of the choices within the limb. Second, although quail pools were known to be compressed into seven rather than eight segments, we show that the map of pools is compressed about a central point (segment three) that preserves the spatial relationships between anterior pools and the crural plexus, and between posterior pools and the sciatic plexus. Access to guidance cues that are restricted to each plexus region is thus maintained between species. Third, pool position along the anterior-posterior axis is the least similar parameter between species. In fact, the entire lumbosacral motor complex may shift by +/- half a segment in individual quail. Despite the consequent differences in segmental projections, the specific projection pattern within each quail hindlimb is identical to that in the chick. There is no need to preserve the exact segmental pattern either phylogenetically or during development, because motoneurons accommodate to modest variations in their position along the anterior-posterior axis by sorting out at the limb base. The contrast between variable segmental and constant limb projections also demonstrates that neither the specification nor the precise projection of motoneurons is dependent upon the specification or development of somites. PMID- 2229474 TI - Muscarinic cholinergic receptors in the songbird and quail brain: a quantitative autoradiographic study. AB - In order to clarify the neuroanatomical basis for postulated muscarinic cholinergic control of a wide array of physiological processes in birds, the distribution of muscarinic cholinergic receptors in the brain of three avian species was investigated by quantitative autoradiography. The species consisted of two passerines (songbirds), the European starling (Sturnus vulgaris) and the song sparrow (Melospiza melodia), and one galliform, the Japanese quail (Coturnix coturnix japonica). [3H]N-methyl scopolamine (NMS), a muscarinic cholinergic antagonist was used as the ligand to label the receptors. Initial experiments demonstrated that the binding of this ligand in the three species is saturable in the nanomolar range and has a high affinity (Kd = +/- 0.6 nM). Displacement experiments revealed that three muscarinic ligands competed in an order of potency characteristic of the mammalian muscarinic receptor (i.e., atropine greater than oxotremorine greater than carbachol) for NMS binding in the avian brain. In all three species, portions of the basal ganglia, such as the parolfactory lobe and the paleostriatum augmentatum, exhibited the highest density of binding. On the other hand, the paleostriatum primitivum, the avian homologue of the mammalian globus pallidus, contained very few binding sites. Other telencephalic sites, such as the ventral and dorsal hyperstriatum, also revealed relatively high receptor density. However, the neostriatum and especially the ectostriatum showed much lower levels. In the hypothalamus, in all three species, specific binding could be observed in the ventromedial nucleus and adjacent areas. The paraventricular nucleus also showed moderate levels of binding density, especially in the two songbird taxa. At a more rostral level, the preoptic area showed low levels of binding. In the quail, the sexually dimorphic nucleus of the preoptic area was clearly outlined in the autoradiograms by the low level of binding sites compared to the surrounding areas. In the two passerine species, nuclei of the song system were identified by either high or low levels of NMS binding. High binding defined area X and the mesencephalic nucleus, intercollicularis (ICo). In contrast, the robust nucleus of the archistriatum and the magnocellular nucleus of the anterior neostriatum showed low levels of binding in comparison with the surrounding tissue. None of these nuclei were visible in the quail autoradiograms except for ICo, which appeared as in the passerines as a heavily labelled area surrounding the lightly labelled nucleus mesencephalicus lateralis pars dorsalis. In all three species, the hippocampal complex was devoid of NMS binding except for two lateral dark bands that were present along the entire rostral to caudal extent of the hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2229475 TI - Topographic disorganization of the optic tracts following long-term optic nerve regeneration: a quantitative image analysis study. AB - Experiments were designed to find the degree to which regenerated optic axons occupied their previous locations in the optic tracts. Following optic nerve crush and regeneration, either the dorsal, ventral, peripheral, temporal, or nasal part of the retina was ablated. The axons of the remaining retinal ganglion cells (RGCs) were labeled with cobalt. Density of the regenerated dorsal and ventral axons in the dorsal vs. ventral optic tracts was determined digitally. In addition, we determined the density of temporal and nasal axons in the temporal vs. nasal compartments of each optic tract and the density of central axons in the central vs. peripheral compartments of both optic tracts. Regenerated axons were not distributed randomly in the optic tracts. Instead, they were slightly but, significantly biased toward growing through the tract or compartment that they had occupied previously. Still, the pathway specificity exhibited by the regenerated axons was closer to random than it was to the pathway specificity seen in normal animals. Dorsal, ventral, and central RGC axons were significantly better localized to their correct tract or compartment than were temporal or nasal RGC axons. Also, over time, dorsal and ventral axons tended to disappear from incorrectly chosen optic tracts. The slight bias toward choosing the appropriate optic tract or optic tract compartment may be enough to account for the topographic specificity of the regenerated retinotectal projection. Near randomness of the axonal positions in the tracts argues against the presence of any specific guidance cues in the optic tracts of adult animals. Axonal density was highest in the correct compartment and diminished progressively with increasing distance into the incorrect compartment. Such a gradient of axonal density suggests that regenerating axons "drift" away from their previous positions in the optic pathways. PMID- 2229476 TI - Development redistribution of photoreceptors across the Macaca nemestrina (pigtail macaque) retina. AB - Redistributions of monkey cones and rods during the first year after birth include a fivefold increase in peak foveal cone density from 43,000 to 210,000 cones/mm2, a decrease in the diameter of the rod-sparse area, and a two- to threefold decrease in peripheral photoreceptor density. Two weeks before birth, higher cone density is already apparent in the future fovea, as are the nasotemporal asymmetry in cone distribution, a higher density "cone streak" along the horizontal meridian, a large rod-sparse central fovea, and a ring of high rod density. Despite the early appearance of these basic patterns, photoreceptor distribution is not mature until 1 to 5 years postnatally. Total cones varied from 4 million at birth to 3.1 million in the average adult. The two oldest eyes had fewer cones, suggesting up to a 25% loss late in development. There were 60 to 70 million rods in the adult macaque retina and little evidence of postnatal changes in number. Neither of these small changes is sufficient to account for the reduction in peripheral photoreceptor density and both are in the wrong direction to explain increasing foveal density, ruling out a major role for either photoreceptor death or generation. Retinal area increased by a factor of 2.4 from 2 weeks before birth to adulthood. In contrast, the posterior pole of the retina was dimensionally stable throughout this period, with the distance between the fovea and optic disc varying nonsystematically from 3.37 to 4.05 mm. Retinal coverage of the globe was also stable at 48-60%. Thus postnatal growth can be ruled out as a factor in the density changes occurring in central retina. Adult retinas have a higher proportion of both cones and rods in midperiphery, whereas young retinas have a higher proportion of photoreceptors in far periphery. It appears that photoreceptors are radially redistributed from peripheral toward central retina during postnatal development, resulting in the marked increase in foveal cone density and the decrease in the eccentricity of the rod ring. Up to 13 weeks postnatally, midperipheral growth of the retina is substantial and increases with eccentricity. At later ages, expansion continues only in the very far periphery. Retinal growth appears sufficient to explain the decreases in peripheral rod and cone density with age. These and previous data strongly suggest that differentiated photoreceptors, with complex cytology and synaptic contacts, migrate toward the foveal center, explaining the increase in foveal photoreceptor density.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2229477 TI - Immunocytochemical localization of protein kinase C subspecies in the rat spinal cord: light and electron microscopic study. AB - Distinct expression of protein kinase C (PKC) subspecies in the central nervous system suggested that each subspecies has a distinct neural function in the processing and modulation of a variety of physiological responses to external signals. In this study, the cellular and subcellular distributions of beta I-, beta II- and gamma-subspecies of PKC were demonstrated by using subspecies specific antibodies in the rat spinal cord. By light microscopy both gamma- and beta II-subspecies immunoreactivities were found only in neurons of the substantia gelatinosa and axons of the dorsal corticospinal tract in the spinal cord. Use of a double staining method, however, revealed that beta II-subspecies immunoreactivity was localized in the outer part of the lamina II, whereas gamma subspecies immunoreactivity was found in the inner part of lamina II. Immunoreactive neurons containing beta I-subspecies were scattered in the substantia gelatinosa. Beta I-subspecies immunoreactivity varied in neuronal types. Furthermore, electron microscopic analysis clearly showed the subcellular distribution of these subspecies to be different from one another. Dense gamma subspecies immunoreactivity was found in the cytoplasm except within cell organelles of the perikarya and dendrites. Some nuclei were stained as strongly as the cytoplasm and others were stained less heavily. The nucleoli had faint or no immunoreactivity. Reaction products of beta II-subspecies were located against the inner plasma membrane but not seen in the nuclei or nucleoli. Beta I subspecies immunoreactivity appeared to be associated with the Golgi complex. No immunoreactive products of any PKC subspecies were detected in the presynaptic terminals. The different patterns of expression described above imply that individual PKC subspecies may have a specific function in modulating the neuronal activity in the different neurons of the spinal cord. PMID- 2229478 TI - Direct catecholaminergic innervation of primate spinothalamic tract neurons. AB - Catecholaminergic axonal varicosities identified by immunocytochemical staining for dopamine-beta-hydroxylase were observed at the light microscopic level apposing the somata of retrogradely labeled spinothalamic tract neurons in the monkey spinal cord. Three retrogradely labeled and two intracellularly labeled spinothalamic neurons were serially sectioned and examined at selected intervals at the electron microscopic level. Electron microscopic study revealed that axonal boutons directly contacted the somata and/or dendrites of lamina I, IV, and V spinothalamic tract neurons. All of the profiles apposing one of the retrogradely labeled lamina I spinothalamic tract neurons were categorized from eight planes of section spaced at 1-micron intervals. Of the 305 profiles counted that were adjacent to this soma, 17 (5.6%) stained positively for dopamine-beta hydroxylase. Of these 17 appositions, three were followed in serial sections to confirm that they had synaptic thickenings and alignment of vesicles along the membrane contacting the spinothalamic tract soma. Catecholaminergic boutons were observed apposing the somata and dendrites of intracellularly filled STT cells characterized as high threshold and wide dynamic range neurons. These observations clearly indicate a direct innervation of spinothalamic tract neurons by catecholaminergic neurons, providing anatomical data to support previous physiological findings demonstrating that catecholamines modulate nociceptive transmission. PMID- 2229479 TI - Distribution of Met-enkephalin, Leu-enkephalin, substance P, neuropeptide Y, FMRFamide, and serotonin immunoreactivities in the optic tectum of the Atlantic salmon (Salmo salar L.). AB - The distribution of the neuropeptides methionine- and leucine-enkephalins, substance P, FMRFamide, neuropeptide Y, and vasoactive intestinal peptide, as well as the biogenic amine serotonin was studied in the optic tectum of the Atlantic salmon by means of immunocytochemistry. Peroxidase-antiperoxidase and indirect immunofluorescence methods were used to compare the differential laminar distribution of each of these substances. Nine parts of the optic tectum were selected for analysis on frontal sections: median, dorsolateral, and ventrolateral areas at rostral, medial, and caudal levels. Methionine- and leucine-enkephalin immunoreactive fibers were found in discrete sublayers in the following strata: stratum opticum, stratum fibrosum et griseum superficiale, stratum griseum centrale, stratum, and album centrale. Most of the substance P-, serotonin-, and vasoactive intestinal peptide-immunoreactive fibers were found in the stratum album centrale, whereas the FMRFamide- and neuropeptide Y immunoreactive fibers were more or less randomly distributed within most of the strata of the optic tectum. Neuropeptide Y-immunoreactive cell bodies were located in the stratum periventriculare. We suggest an extrinsic origin for most of the immunoreactive fibers observed in the optic tectum, except for the neuropeptide Y-immunoreactive fibers that probably originate in the periventricular neurons. Although retinal peptidergic input to the optic tectum has been proposed in other vertebrates, there is no evidence that any of the neuropeptidelike or serotonin immunoreactive fibers in the optic tectum of the salmon should be of retinal origin. Differences and similarities with the distribution of neuropeptides in the optic tectum in representatives of other vertebrate classes are discussed. PMID- 2229480 TI - Morphology of a population of mechanosensory ascending interneurones in the metathoracic ganglion of the locust. AB - A population of ascending interneurones with cell bodies in the metathoracic ganglion of the locust is described. Interneurones are characterised by their morphology (revealed by intracellular cobalt injection) and by their physiological responses to afferent stimulation. All interneurones have their somata in the ventral cortex of the ganglion, in an area just posterior to the medial tracheae. On the basis of gross morphology the interneurones can be divided into three groups: (1) those that have a main area of fine neurites ipsilateral to the soma and an ipsilateral ascending axon; (2) interneurones that also have their main neurites ipsilateral to the soma but have a contralateral ascending axon, and (3) interneurones that have their main stimulation of sensory receptors on the hind leg ipsilateral to the main neurites. Interneurones receiving excitatory inputs from tactile hairs on the hind leg have branches in the most ventral neuropil, whereas interneurones receiving input from leg proprioceptors have branches in the more intermediate and dorsolateral neuropil. The branching pattern of an interneurone and the size and position of the receptive field on the leg are correlated. Interneurones with restricted branching patterns have restricted receptive fields. The position of the ventral branching reflects the position of the receptive field on the leg. An interneurone with a receptive field restricted to the femur has ventral branches in an anterior position in the ganglion; an interneurone with a receptive field restricted to the tarsus has ventral branches in a more posterior position. PMID- 2229481 TI - Morphological variability, segmental relationships, and functional role of a class of commissural interneurons in the spinal cord of goldfish. AB - As part of an attempt to understand the spinal control of the segmented axial musculature in goldfish, commissural spinal interneurons that are electronically coupled to the Mauthner axon (M-axon) were studied with intracellular recording and staining to examine their morphology, segmental relationships, and functional role. Prior studies suggested that these cells might mediate the crossed inhibition that blocks excitation of motoneurons on one side of the body during an escape bend to the opposite side. Simultaneous intracellular recordings from a M-axon, a commissural interneuron coupled to it, and a presumed primary motoneuron show that: (1) the interneurons produce monosynaptic, Cl(-)-dependent IPSPs in contralateral motoneurons, (2) the interneurons are responsible for the short latency, crossed spinal inhibition in the M-cell network, and (3) more than one interneuron terminates on each postsynaptic cell. Reconstructions of interneurons from wholemounts show that they form a fairly homogeneous morphological class of cells. Each one is unipolar, with an axon that crosses the cord and then usually bifurcates into a short, thin ascending branch and a thicker, longer descending one. Neighboring interneurons have overlapping terminal arbors consistent with the physiological data showing convergence of interneurons onto the same postsynaptic cell. The interneurons showed little relationship with body segments as defined by ventral roots. Their axons usually straddled segmental boundaries, with terminals typically occupying parts of two adjacent segments. Thus the functional unit of these cells is probably not a segment or a complete group of segments, but instead includes only parts of two adjacent segments. The presence of interneurons like these suggests that the overt peripheral segmentation of trunk musculature is not necessarily reflected in the organization of neurons that control those segments. A consideration of some functional characteristics of the activation of overlapping, serially repeated arrays of interneurons by descending pathways leads to the conclusion that the high conduction velocity of the M-axon, and the large size and short longitudinal extent of the axons of the inhibitory interneurons promote a strong, brief inhibition that is appropriate for the production of an escape turn that has a rapid bend to one side. PMID- 2229482 TI - DARPP-32, a phosphoprotein enriched in dopaminoceptive neurons bearing dopamine D1 receptors: distribution in the cerebral cortex of the newborn and adult rhesus monkey. AB - DARPP-32, a dopamine (DA) and cAMP-regulated phosphoprotein, is associated with dopaminoceptive neurons bearing D-1 receptors in the basal ganglia. The present study addressed the distribution of DARPP-32 in the primate cerebral cortex and its putative association with D-1 receptor laden cells in this structure. DARPP 32-like immunoreactive (LIR) neurons were examined in the cerebral cortex of 3 day-old (P3), 6-week-old (P42), and adult rhesus monkeys. In the younger cases, a large number of DARPP-32 positive neurons, with the morphological characteristics of pyramidal cells, were observed throughout the cortex, in layers V-VI, and to a lesser extent in layer II and uppermost layer III. In the parietal, insular, temporal, and occipital cortices, DARPP-32 positive neurons were arranged in a monolayer in layer Va. They were often clustered in small groups with a bundling of their dendrites. In the primary motor cortex, Betz cells were among the labeled population. In the association and somatosensory areas, the basal dendrites of DARPP-32 positive neurons and the prominent tufting of their apical dendrites in layer I contributed to an essential bilaminar pattern resembling the distribution reported for DA afferents and D-1 receptors in these areas. The prominence and widespread distribution of DARPP-32 positive neurons in layer V may be a specialization of primate cortex since such cells are found only in restricted locations in rodents. The literature on the connections of the cerebral cortex suggests that a large number of the DARPP-32 positive neurons in layer VI and perhaps even in layer Va may be corticothalamic neurons. An important developmental observation was the presence of DARPP-32-LIR neurons in the white matter. They were prominent in the neonates but could not be seen in the adult. Their location as well as their type and shape were reminiscent of interstitial neurons. In the adult monkeys, the distribution of DARPP-32-LIR neurons was more circumscribed: they were numerous in the ventral temporal gyrus and in areas related to the limbic system: caudal orbitofrontal cortex, insula, temporal pole, entorhinal, and anterior cingulate cortex. Weak labeling was detected in layer Va of the superior temporal and parietal cortex, in some prefrontal areas (10, 13, and medial 9), and in the premotor and supplementary motor cortex; in adults, unlike neonates, few DARPP-32-LIR neurons were present in the dorsolateral prefrontal cortex, the primary motor or the primary visual or prestriate cortices.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2229483 TI - Renewal of electrotonic synapses in teleost retinal horizontal cells. AB - In teleost retinas, the somata of same-type cone horizontal cells are electrically coupled via extensive gap junctions, as are the axon terminals of same-type cells. This coupling persists throughout the animal's life and is modulated by dopamine and conditions of light- vs. dark-adaptation. Gap junction particle density in goldfish horizontal cell somata has also been shown to change under these conditions, indicating that these junctions are dynamic. We have used electron microscopy to examine gap junctions in bass horizontal cells with a fixation method that facilitates detection of gap junctions. Annular gap junction profiles were observed in the somatic cytoplasm of all cone horizontal cell types in both light- and dark-adapted animals. Serial sections showed that most profiles represented gap junction vesicles free within the cytoplasm; the remainder represented vesicles still attached to extensive plasma membrane gap junctions by a thin cytoplasmic neck, suggestive of an intermediate stage in endocytosis. Observations of gap junction vesicles containing fragments of gap junctional membrane and/or fused with lysosomal bodies further supported this hypothesis. Because gap junctions persist between the horizontal cells, we propose that gap junction endocytosis and lysosomal degradation are balanced by addition of new junctions. While endocytosis has been widely demonstrated to serve in programmed removal of gap junctions (without subsequent replacement), from both nonneuronal cells and developing neurons, this study indicates that it can also function in the renewal of electrical synapses in the adult teleost retina, where gap junction elimination is not the goal. PMID- 2229484 TI - Rafael Lorente de No: 1902-1990. PMID- 2229485 TI - Single fiber studies of ascending input to the cuneate nucleus of cats: I. Morphometry of primary afferent fibers. AB - The morphology of afferent fibers ascending to the cuneate nucleus has been examined in this and the subsequent paper in order to quantify the pattern of arborization and bouton arrangement of selected classes of primary afferents and to compare these data with data from postsynaptic fibers ascending to the cuneate nucleus. Electrophysiologically identified G hair and Ia muscle afferent fibers in the cuneate fasciculus were intraaxonally injected with horseradish peroxidase. Cutaneous afferents terminated dorsal to proprioceptive afferents, especially at middle levels of the cuneate nucleus. The spacing of collaterals along G hair fibers was variable, but averaged 1.46 collaterals per mm; collateral density was higher at middle cuneate levels than in the rest of the nucleus. Collateral density of Ia fibers was lower than for G hair fibers and was lowest at caudal levels of the nucleus. Branches of G hair collaterals, though often initially diverging, usually converged to terminate in a single focus in the dorsal part of the nucleus. The probability of bifurcation of Ia collaterals decreased steadily at successive branch points. These collaterals branched less symmetrically than G hair collaterals, and terminated in the ventral cuneate with less dense arbors, stretched mediolaterally, but of comparable cross-sectional area. Individual G hair collaterals gave rise to more boutons than Ia collaterals; in both cases they were mostly of the en passant type. Boutons were restricted to distal branches of G hair collaterals, whereas boutons of Ia collaterals were also located on proximal branches. Bouton size was similar for the two classes of collaterals. The data reported here, in combination with the published literature, suggest that the collaterals of roughly 300 G hair fibers overlap at any given point at middle levels of the cuneate nucleus. This high degree of anatomical convergence is not predicted by the functional segregation described with electrophysiological mapping, implying the presence of intrinsic nuclear mechanisms enhancing response specificity. PMID- 2229486 TI - Cortical neurons expressing the cholecystokinin gene in the rat: distribution in the adult brain, ontogeny, and some of their projections. AB - Recent studies of neuronal cholecystokinin (CCK) expression performed with more sensitive techniques have demonstrated that the distribution of the expression of this peptide is more widespread than previously thought. In the present study, hybridization histochemistry was used to map cortical neurons expressing the CCK gene in adult and developing rats. Retrograde tracing with Fluorogold in combination with hybridization histochemistry was used to demonstrate some of the projections of these neurons. Neurons expressing the CCK gene were found in all areas of the neo- and allocortices. They were of several morphological types, including pyramidal neurons, and were found in almost all layers, albeit at different relative numbers and with different levels of expression. Generally, layers II and III, deep layer V, and layer VI had many neurons expressing CCK mRNA. Cortical CCK expression was first detected on the 15th day of gestation in the primordial plexiform layer. Expression developed thereafter in a regular and continuous fashion until an adult-like pattern was present on the 21st day after birth. Cortical neurons containing CCK mRNA were found in almost all the projections studied. Many neurons in both neo- and allocortical areas with cortico-cortical, associational, and commissural pathways contained CCK mRNA. Similarly, numerous corticostriatal neurons contained CCK mRNA; however, only a few corticothalamic neurons expressed CCK mRNA. These results demonstrate that in the rat cortex the distribution of projection neurons expressing CCK is much more widespread than had been previously shown and will stimulate further investigations into the role of CCK in these neurons. PMID- 2229487 TI - Topography of ganglion cells in human retina. AB - We quantified the spatial distribution of presumed ganglion cells and displaced amacrine cells in unstained whole mounts of six young normal human retinas whose photoreceptor distributions had previously been characterized. Cells with large somata compared to their nuclei were considered ganglion cells; cells with small somata relative to their nuclei were considered displaced amacrine cells. Within the central area, ganglion cell densities reach 32,000-38,000 cells/mm2 in a horizontally oriented elliptical ring 0.4-2.0 mm from the foveal center. In peripheral retina, densities in nasal retina exceed those at corresponding eccentricities in temporal retina by more than 300%; superior exceeds inferior by 60%. Displaced amacrine cells represented 3% of the total cells in central retina and nearly 80% in the far periphery. A twofold range in the total number of ganglion cells (0.7 to 1.5 million) was largely explained by a similar range in ganglion cell density in different eyes. Cone and ganglion cell number were not correlated, and the overall cone:ganglion cell ratio ranged from 2.9 to 7.5 in different eyes. Peripheral cones and ganglion cells have different topographies, thus suggesting meridianal differences in convergence onto individual ganglion cells. Low convergence of foveal cones onto individual ganglion cells is an important mechanism for preserving high resolution at later stages of neural processing. Our improved estimates for the density of central ganglion cells allowed us to ask whether there are enough ganglion cells for each cone at the foveal center to have a direct line to the brain. Our calculations indicate that 1) there are so many ganglion cells relative to cones that a ratio of only one ganglion cell per foveal cone would require fibers of Henle radiating toward rather than away from the foveal center; and 2) like the macaque, the human retina may have enough ganglion cells to transmit the information afforded by closely spaced foveal cones to both ON- and OFF-channels. Comparison of ganglion cell topography with the visual field representation in V1 reveals similarities consistent with the idea that cortical magnification is proportional to ganglion cell density throughout the visual field. PMID- 2229488 TI - Morphology of the octopus cell area of the cochlear nucleus in young and aging C57BL/6J and CBA/J mice. AB - The influence of aging and age-related cochlear impairment on the ventral cochlear nucleus was evaluated by measuring morphological properties of the octopus cell area (OCA) in five age groups of inbred C57BL/6J and CBA/J mice (young adult to very old). The former strain demonstrates progressive cochlear sensorineural pathology and hearing loss during middle age; the latter has only modest sensorineural pathology late in life. Histological sections of the OCA were evaluated with serial sections and several strains for neurons, glia, and fibers, and Golgi impregnations were also used. Aging was associated with a decrease in volume of the OCA, a loss of neurons, slight decrease in neuron size, increased packing density of glial cells, and changes in dendrites ranging from minor to total loss of primary branches. The greatest changes occurred in extreme old age, beyond the median lifespan. Age-related changes were not exacerbated by sensorineural pathology in aging C57BL/6J mice. Individual octopus cells varied greatly in the extent of age-related abnormality. PMID- 2229489 TI - Distribution of cholecystokinin-like-immunoreactive neurons in the guinea pig forebrain. AB - The distribution of cholecystokinin (CCK)-immunoreactive nerve fibers and cell bodies was studied in the forebrain of control and colchicine-treated guinea pigs by using an antiserum directed against the carboxyterminus of CCK octapeptide (CCK-8) in the indirect immunoperoxidase technique. Virtually all forebrain areas examined contained immunoreactive nerve fibers. A dense innervation was visualized in; neocortical layers II-III, piriform cortex, the medial amygdala, the medial preoptic area, a circumventricular organ-like structure located at the top of the third ventricle in the preoptic area, the subfornical organ, the posterior bed nucleus of the stria terminalis, the posterior globus pallidus (containing labeled woolly fiber-like profiles), the ventromedial hypothalamus, the median eminence, and the premammillary nucleus. A moderately dense innervation was visualized elsewhere excepted in the septum and thalamus where labeled axons were comparatively few. Immunoreactive perikarya were abundant in: neocortex (especially layers II-III), piriform cortex, amygdala, the median preoptic nucleus, the bed nucleus of the stria terminalis, the hypothalamic paraventricular (parvicellular part), arcuate, and dorsomedial (pars compacta) nuclei, the dorsal and perifornical hypothalamic areas, and throughout the thalamus. Areas also containing a moderate number of labeled cell bodies were the medial preoptic area, the globus pallidus, the caudate-putamen, and the periventromedial area in the hypothalamus. Immunostained perikarya were absent or only occasionally observed in the septum, the suprachiasmatic nucleus, the magnocellular hypothalamoneurohypophyseal nuclei, and the ventral mesencephalon. In the adenohypophysis, corticomelanotrophs were labeled in both males and females, and thyrotrophs were labeled in females only. This distribution pattern of CCK-8 immunoreactivity is compared to those previously recorded in other mammals. This shows that very few features are peculiar to the the guinea pig. It is discussed whether some interspecific differences in immunostaining are real rather than methodological. PMID- 2229490 TI - Sustained improvement with prolonged topical tretinoin (retinoic acid) for photoaged skin. AB - We performed a 22-month trial of topical tretinoin (retinoic acid) in the treatment of photoaging. Thirty patients participated in a 4-month, randomized, blinded, vehicle-controlled study that has been reported previously; 21 patients continued tretinoin therapy on an open-label basis, participating in the study for a total of 10 months, and 16 patients continued for 22 months. During the open-label study, the statistically significant improvement that had occurred in fine and coarse wrinkling and skin texture during our original study was sustained, despite reductions in dose or frequency of application of tretinoin. The number of discrete lentigines decreased by 71% compared with the number before therapy. Histologic findings included a statistically significant thickening of the epidermis. Side effects were limited to a cutaneous retinoid reaction that diminished as therapy proceeded. PMID- 2229491 TI - The Muir-Torre (Torre's) syndrome: the significance of a solitary sebaceous tumor. PMID- 2229492 TI - Identification of human immunodeficiency virus hybridizing sequences in the peripheral blood of a patient with systemic lupus erythematosus. AB - Systemic lupus erythematosus, a multisystemic disorder, is considered a prototype of the autoimmune diseases. Although its cause remains unknown, a viral etiology has been proposed. We report that a rapid and sensitive messenger RNA in situ hybridization technique detected hybridizing sequences to the human immunodeficiency virus type in the peripheral blood cells of a woman with systemic lupus erythematosus in whom the presence of acquired immuno-deficiency syndrome was reasonably excluded. PMID- 2229493 TI - Cutaneous manifestations of postthymic T cell malignancies: description of five clinicopathologic subtypes. AB - This study was undertaken to identify the cutaneous manifestations among different prognostic subgroups of postthymic T cell malignancies. Cutaneous involvement was demonstrated in 43 of 88 cases. We recognized five clinicopathologic subtypes: type I, classical cutaneous T cell lymphoma (CTCL) or mycosis fungoides, six cases; type II, primary large cell type CTCL, Ki-1 antigen (Ki-1+ or Ki-1-), seven cases; type III, primary angioinvasive T cell lymphoma, three cases; type IV, human T-lymphotropic virus type I (HTLV-I+) adult T cell leukemia/lymphoma (ATL), eight cases; type V, secondary cutaneous involvement by peripheral T cell lymphoma (PTL), 19 cases. Primary CTCL and ATL tend to involve papillary dermis with or without epidermotropism, whereas PTL and angioinvasive T cell lymphoma predominantly affect skin adnexae, vessels, and subcutis. Cutaneous lesions in type V PTL are heterogeneous and may be confused with panniculitis, vasculitis, or an eczematous eruption. Classic CTCL, Ki-1+ lymphoma, and angioinvasive T cell lymphoma have a chronic course, whereas ATL, Ki-1- large cell lymphoma, and PTL are clinically aggressive. PMID- 2229494 TI - Hypergammaglobulinemic purpura of Waldenstrom. AB - Hypergammaglobulinemic purpura of Waldenstrom is characterized by hypergammaglobulinemia, recurring purpura, an elevated erythrocyte sedimentation rate, and the presence of rheumatoid factor indicative of circulating immune complexes. There is a significant association with autoimmune diseases, especially Sjogren's syndrome and lupus erythematosus. Hypergammaglobulinemic purpura is considered primary when there is no other associated disease or secondary when associated with other diseases, usually autoimmune. Immune derangements are fundamental in its pathogenesis, although its cause is still unknown. Therapy is unrewarding and is probably unnecessary for this usually benign condition. Three cases are presented that are representative of patients with hypergammaglobulinemic purpura. PMID- 2229495 TI - Treatment of idiopathic guttate hypomelanosis with liquid nitrogen: light and electron microscopic studies. AB - Idiopathic guttate hypomelanosis is a common skin disorder of unknown cause. Our studies have shown that significantly fewer dopa-positive melanocytes are in the white macules of idiopathic guttate hypomelanosis than in normal skin. By electron microscopy we observed that the melanocytes in the lesional skin were round and less dendritic with fewer melanosomes than in normal pigment cells. Lesions gently frozen with liquid nitrogen repigmented in 6 to 8 weeks. The number of dopa-positive melanocytes was significantly greater in the repigmented areas than in untreated lesions but less than in normal skin. PMID- 2229496 TI - Treatment of molluscum contagiosum using a lidocaine/prilocaine cream (EMLA) for analgesia. AB - Eighty-three 4- to 12-year-old children, scheduled for curettage of at least five molluscum contagiosum lesions, participated in a double-blind study. The children were randomly allocated to receive lidocaine/prilocaine (EMLA) cream (n = 58) or placebo cream (n = 25), applied 15, 30, or 60 minutes before treatment. The pain was assessed by the children and the physician as none, slight, moderate, or severe. In addition, the children rated the pain on a visual analog scale. EMLA cream effectively prevented the pain after all three application times (p less than 0.01). No significant difference in pain was observed among the 15-, 30-, and 60-minute EMLA-treated groups, but the proportion of children reporting no pain on the verbal scale increased from 36% in the 15-minute group to 61% in the 60-minute group. In the placebo group, only one of 24 children (4%) reported no pain. Transient local redness was the only skin reaction noted. In conclusion, an application time of EMLA cream of less than 60 minutes is satisfactory for the curettage of molluscum contagiosum in children. PMID- 2229498 TI - Prolonged remission after cyclosporine therapy in pemphigus vulgaris: report of two young siblings. AB - We report the clinical evolution of two young siblings with severe pemphigus vulgaris treated with cyclosporine for 30 and 12 months, respectively. One was resistant to treatment with high-dose corticosteroids and azathioprine. A good clinical response was achieved in both cases. No major side effects were observed. The patients have remained disease free for more than 20 months after stopping cyclosporine therapy. PMID- 2229497 TI - Intralesional interferon therapy for basal cell carcinoma. AB - In a clinical trial of 172 patients at four medical centers, interferon alfa-2b (1.5 x 10(6) IU) or a placebo was injected directly into biopsy-proved noduloulcerative or superficial basal cell carcinomas three times weekly for 3 weeks, for a cumulative dose of 13.5 million IU. Efficacy of treatment was determined at 16 to 20 weeks by examination of biopsy specimens that demonstrated cure of lesions in 86% of interferon-treated patients and in only 29% of placebo treated patients. During the treatment course and follow-up, an initial inflammatory response was observed at the treatment sites, followed by diminished erythema, improvement in overall appearance, and a decrease in size of lesions. Side effects of treatment, mainly flu-like symptoms, were usually mild and transient and occurred more commonly in the interferon-treated group. Only three patients, all in the interferon-treated group, discontinued therapy because of side effects. One year after initiation of therapy, 81% of interferon recipients and 20% of those given the placebo remained tumor free. Noduloulcerative and superficial lesions were equally responsive to treatment with interferon. For some patients with noduloulcerative or superficial basal cell carcinomas, intralesional interferon alfa-2b may be an alternative, effective treatment. PMID- 2229499 TI - Extracorporeal photopheresis in psoriasis vulgaris: clinical and immunologic observations. AB - Four patients with chronic refractory plaque-type psoriasis without arthropathy were treated with extracorporeal photopheresis every other week for 6 to 13 months. In patients 1 and 2, methotrexate was administered concomitantly during the initial part of the trial; the dose was gradually tapered and the drug was discontinued by 6 months. Both patients improved to 23% and 62% of baseline values for percentage of body surface involvement, but their disease then flared when maintenance extracorporeal photopheresis was used alone. Substantial improvement again occurred when lower doses of methotrexate were administered with extracorporeal photopheresis. Patients 3 and 4 were treated initially with extracorporeal photopheresis alone and both improved to 50% and 52% of baseline body surface involvement, respectively, after 4 months of treatment. However, their disease flared because of factors unrelated to treatment. Extracorporeal photopheresis was well tolerated by all patients without evidence of overt toxicity. However, prolonged treatment with extracorporeal photopheresis/methotrexate was accompanied by a decrease in skin reactivity to recall antigens and by decreased capacity of lymphocytes to produce interleukin 2 in response to polyclonal stimuli in vitro. These findings indicate that alternate-week extracorporeal photopheresis has a definite but incomplete suppressive effect on psoriasis vulgaris that may be mediated through an effect on lymphokine production by photomodified cells and that the therapeutic effect of extracorporeal photopheresis may be enhanced by concomitant administration of low doses of methotrexate. PMID- 2229501 TI - Autoimmunity and malignancy. AB - In patients with autoimmune diseases malignancy is observed more frequently than in an age-matched control group. In strains of mice susceptible to autoimmune diseases, the incidence of lymphoreticular malignancies is increased. Although viruses have not been directly implicated in their pathogenesis or etiology, there are suggestions that slow viruses may be involved. Viruses have been found to be important in the development of lymphomas. Hence in genetically susceptible animals, viruses can initiate the autoimmune process. Prolonged stimulation of the autoimmune process or a prolonged state of immunodeficiency could trigger or activate genes or their products, which could result in the development of malignancy. PMID- 2229500 TI - Synthetic membranes and cultured keratinocyte grafts. AB - Significant progress has been made in skin replacement options in the past several decades. Although initially various materials have been used mainly for burn coverage, their application to dermatologic practice has increased significantly. We review the research, progress, and other aspects of wound coverage with synthetic membranes and cultured epithelial sheets in both burn and nonburn wound management. PMID- 2229502 TI - Buschke-Loewenstein tumor: verrucous carcinoma of the penis. AB - The Buschke-Loewenstein tumor is an anogenital tumor of characteristic clinical and histologic pattern best considered as a low-grade, well-differentiated squamous cell carcinoma. This remarkable neoplasm and its features are reviewed in detail, stressing salient advances in our understanding of it. PMID- 2229503 TI - Contact dermatoses from disposable glove use: a review. AB - Contact dermatoses from disposable gloves are being reported with greater frequency. A variety of eruptions can occur. These have become increasingly relevant for dermatologists, who for most procedures now use disposable gloves. This article represents a review of the relevant issues about the use of disposable gloves by dermatologists. Methods of management and prevention of morbidity associated with disposable glove use will also be discussed. PMID- 2229504 TI - Behcet's disease. PMID- 2229505 TI - Blastomycosis-like pyoderma caused by Pseudomonas aeruginosa: report of a case responsive to ciprofloxacin. PMID- 2229506 TI - Familial perifolliculitis capitis abscedens et suffodiens in two brothers successfully treated with isotretinoin. PMID- 2229507 TI - Porokeratosis in a patient treated with total body electron beam radiation. PMID- 2229508 TI - Corticosteroid-induced 'disappearing digit'. PMID- 2229509 TI - Trichonodosis in a patient with straight hair. PMID- 2229510 TI - Palmoplantar pustulosis as a manifestation of cutaneous T cell lymphoma (mycosis fungoides) PMID- 2229512 TI - Superficial epithelioma with sebaceous differentiation. PMID- 2229511 TI - Complete resolution of generalized eczema craquele after treatment with metronidazole of occult amebiasis. PMID- 2229513 TI - Ptychotropism as a cutaneous feature of the CHILD syndrome. AB - The hallmark of the CHILD syndrome is a unilateral ichthyosiform nevus that displays a pronounced affinity for the body folds. For this phenomenon the term ptychotropism is proposed. The expression is composed from the Greek words ptyche (fold) and trope (a turning). It is concluded that the cutaneous lesions of the CHILD nevus are determined by two factors, lyonization and ptychotropism. The phenomenon of ptychotropism constitutes an additional argument to distinguish the CHILD nevus from the inflammatory linear verrucous epidermal nevus because the latter is not ptychotropic. PMID- 2229514 TI - Nocturnal wakening caused by pruritus: organic or psychogenic? PMID- 2229515 TI - Abnormalities in structure and function of the thyroid gland in patients with alopecia areata. PMID- 2229516 TI - Comparative efficacy of two different formulations on xerosis. PMID- 2229517 TI - Psoriasis and tetracyclines. PMID- 2229518 TI - Immunohistologic investigation of the skin in primary Sjogren's syndrome. PMID- 2229519 TI - Jessner-Kanof lesion and Borrelia infection. PMID- 2229520 TI - Recognition of subungual hematoma as an imitator of subungual melanoma. PMID- 2229521 TI - History of antifungals. AB - Until two to three decades ago, only a few drugs were available for the treatment of fungal infections. The status of antifungal therapy changed dramatically in the late 1960s with the introduction of newer broader spectrum agents, such as the iodinated trichlorophenols and the imidazoles, that acted by disruption of the fungal cell membrane. Some of the more recently developed broad-spectrum antifungal drugs include the triazoles terconazole, itraconazole, and fluconazole and the dimethylmorpholine amorolfine. The allylamines represent one of the newest classes of compounds shown to be effective in the management of fungal disorders. The two members of this unique chemical class that have been studied clinically, naftifine and terbinafine, are effective against a wide spectrum of fungal organisms. Terbinafine has the added advantage of both topical and oral activity. PMID- 2229522 TI - Problems of resistant dermatophytes. AB - Recalcitrant fungal infections are defined as infections that are difficult or impossible to eradicate despite seemingly adequate treatment with appropriate oral or parenteral antibiotics. Relative or absolute microbial resistance is only one of the many causes of recalcitrance. Others include failure of the patient to comply with the prescribed treatment regimen, drug degradation in the liver, drug drug interactions, reabsorption or washout of the drug from the stratum corneum, and failure of the drug to reach the stratum corneum. Excretion in the eccrine sweat is the principal pathway by which griseofulvin and ketoconazole, the two currently available oral antifungal agents, are delivered to the stratum corneum. Measures that promote delivery of these drugs to this site by enhancing sweating and minimizing drug run-off and absorption onto clothing may aid in optimizing the therapeutic response to these agents. PMID- 2229523 TI - Pharmacology of the allylamines. AB - The allylamines are a new class of antifungal drugs that inhibit ergosterol synthesis at the level of squalene epoxidase. These agents are highly selective for the fungal enzyme and have a minimal effect on mammalian cholesterol synthesis. Naftifine, the original member of the allylamine series, possesses only topical activity, whereas the naftifine analog terbinafine is active both topically and orally. In vitro, terbinafine is exceptionally active against dermatophytes, molds, and dimorphic fungi in which it exerts a fungicidal action. This in vitro profile is reflected by the clinical effectiveness of this allylamine in the treatment of dermatophyte infections. When given orally, terbinafine is well absorbed and rapidly and extensively distributed to the skin and sebum in concentrations that exceed the minimum inhibitory concentrations of these organisms by several orders of magnitude. PMID- 2229524 TI - Treatment of chronic tinea pedis (athlete's foot type) with topical terbinafine. AB - Twenty-seven patients with chronic tinea pedis, athlete's foot type, were enrolled in a randomized, double-blind trial of topical treatment with terbinafine 1% cream versus its vehicle (placebo). Patients were examined weekly during 4 weeks of twice-daily treatment and at follow-up 2 weeks after the conclusion of therapy. No adverse events were reported in either treatment group. Drug efficacy was evaluated in 22 patients, of whom nine (41%) were treated with terbinafine and 13 (59%) with placebo. Analysis of combined mycologic and clinical results showed that terbinafine was significantly more effective than placebo at the end of therapy (78% vs zero) and at the 2-week follow-up (89% vs zero) (p less than or equal to 0.001 at both intervals. PMID- 2229525 TI - A clinical trial of topical terbinafine (a new allylamine antifungal) in the treatment of tinea pedis. AB - Twenty-three patients were enrolled in a randomized, double-blind trial of terbinafine 1% cream compared with placebo vehicle in the treatment of tinea pedis. Of the 20 patients who were evaluated for efficacy, 10 received terbinafine and 10 received placebo. Except for the terbinafine-treated patients being an average of 11 years older than the patients receiving placebo and the median duration of disease being 6 weeks longer in the placebo group, the two groups were demographically and clinically similar. Results of mycologic tests and clinical findings showed terbinafine to be significantly more effective than placebo in the treatment of tinea pedis. Significantly more terbinafine-treated patients than placebo-treated patients showed conversion to negative culture and microscopy at end of therapy and a significant reduction in scored signs and symptoms. Overall efficacy at follow-up (combined mycologic and clinical findings) was also significantly greater in the terbinafine group (78%) than in the placebo group (zero) (p less than 0.001). Unexplained elevation of liver function test results was noted in three placebo-treated patients and in one terbinafine-treated patient, but these changes were not considered clinically relevant or drug related. PMID- 2229526 TI - Efficacy and tolerability of topical terbinafine in the treatment of tinea cruris. AB - Thirty men with clinical and mycologic evidence of tinea cruris were enrolled in a controlled, randomized, double-blind trial comparing terbinafine 1% cream and its cream vehicle as placebo. Patients applied the test medications to the affected area twice daily for 2 weeks. Therapeutic response was evaluable in 18 patients after each week of treatment and at a follow-up visit 2 weeks after therapy ended. At each visit, terbinafine was found to be more effective than the cream vehicle in the reduction of the signs and symptoms of infection and in the conversion of culture and microscopy findings to negative or normal. At the end of treatment, therapy was effective in 67% of the nine terbinafine-treated patients compared with only 11% of the nine placebo-treated patients. At the follow-up examination, efficacy rates were 78% in the terbinafine treatment group and 33% in the placebo group--a difference of borderline statistical significance (p = 0.077). Possible reasons for this result may include the higher incidence of chronic disease in the terbinafine group and the large number of patients who were classified as delayed exclusions because of negative initial culture for dermatophytes. No side effects or significant alterations in laboratory or hematologic tests were observed in either treatment group. PMID- 2229527 TI - Treatment of tinea cruris with topical terbinafine. AB - Twenty-three patients were enrolled in a randomized, double-blind trial of terbinafine 1% cream versus its vehicle (placebo) in the treatment of tinea cruris. One patient had a negative initial culture and was excluded, and two patients were dropouts, one because of poor study compliance (terbinafine) and one because of an adverse event (placebo). Twenty patients were examined for efficacy of treatment (9 terbinafine-treated, 11 placebo-treated). Both groups were similar in age, sex, duration of disease, prior therapy, size and location of lesion, infecting organism, and predisposing factors. Terbinafine 1% cream was more effective than vehicle cream in the reduction of the signs and symptoms of tinea cruris. In addition, there was a higher conversion rate to negative culture and normal microscopy findings in the terbinafine-treated group. Clinical results combined with evaluation of mycologic tests at end of therapy showed terbinafine to be a rapid and significantly more effective treatment for tinea cruris than placebo (78% vs 18% cure rate, respectively). Follow-up cure rates confirmed these findings (89% and 18%, respectively). No significant adverse events occurred during terbinafine treatment. PMID- 2229528 TI - Treatment of chronic moccasin-type tinea pedis with terbinafine: a double-blind, placebo-controlled trial. AB - Terbinafine is an orally and topically active fungicidal drug of the allylamine series. Its oral efficacy at 125 mg taken twice daily was evaluated in a randomized, double-blind, placebo-controlled study in moccasin-type tinea pedis. The study was conducted simultaneously in two centers and consisted of 41 evaluable cases (23 terbinafine, 18 placebo). Mycologic cure and near to complete clearing of signs and symptoms were obtained in 59% of the terbinafine-treated patients after 6 weeks of treatment and in 65% at 2 weeks after treatment. Corresponding efficacy for placebo-treated patients was zero at both evaluations. Side effects in both groups were minimal. We conclude that terbinafine is well tolerated and highly effective in moccasin-type tinea pedis. PMID- 2229529 TI - Oral terbinafine versus griseofulvin in the treatment of moccasin-type tinea pedis. AB - The safety and effectiveness of oral terbinafine, 125 mg twice daily, and griseofulvin, 250 mg twice daily, in patients with moccasin-type tinea pedis were examined in a double-blind randomized trial. At the end of the 6-week treatment period, both a clinical and mycologic cure or a mycologic cure with minimal signs of infection was noted in 12 (75%) of the 16 terbinafine-treated patients compared with only 3 (27%) of the 12 patients treated with griseofulvin. The overall response rate 2 weeks after the completion of treatment was 88% in the terbinafine-treated group and 45% in the griseofulvin-treated group. When contacted again 6 to 15 months after completion of the study, 94% of the terbinafine-treated patients reported sustained clearing of tinea pedis, and 88% of those with nail involvement at the time of treatment reported improvement. In contrast, tinea pedis remained cured in only 30% of the patients who had received griseofulvin, and onychomycosis improved in only 14%. PMID- 2229530 TI - Cutaneous melanoma and bilateral retinoblastoma. AB - We report the case of an otherwise healthy 37-year-old man who had had bilateral enucleation during early childhood for bilateral retinoblastomas, in addition to two cutaneous melanomas (the first appearing at age 27 years). He also had dysplastic melanocytic nevi and a history of cutaneous melanoma in his mother. Retinoblastoma may aggregate in families and is associated with DNA abnormalities of chromosome 13. Recent reports have emphasized the appearance of second malignancies in retinoblastoma survivors. The second malignancies include osteosarcoma, soft tissue sarcoma, and cutaneous melanoma. Cutaneous melanoma also may aggregate in families, usually in the setting of dysplastic melanocytic nevi. The features of this case and of similar reported cases suggest that there may be a greater than expected association between retinoblastoma and cutaneous melanoma. PMID- 2229531 TI - Multicentric cloacogenic carcinoma: report of a case with anogenital pruritus at presentation. AB - A case of multicentric cloacogenic carcinoma of the perianal skin and vulva in a 79-year-old woman is presented, and the embryologic basis for the multicentricity is discussed. Histologically, cloacogenic carcinoma can be differentiated from other small cell neoplasms that affect the area. Cloacogenic carcinoma should be considered a rare cause of anogenital pruritus. It is important to perform an early biopsy of anogenital lesions that do not respond to conventional therapy. PMID- 2229532 TI - Eosinophilic pustular folliculitis: fungal folliculitis? AB - Eosinophilic pustular folliculitis is a rare condition with no known cause. However, a fungal cause is suggested by (1) tinea-like annular lesions, (2) initial clinical consideration of fungal folliculitis in many reported cases, (3) an association with the acquired immunodeficiency syndrome, and (4) an association with scaly and vesiculopustular lesions of palms and soles. We report a case histologically identical to eosinophilic pustular folliculitis but in which hyphal fungal organisms were demonstrated in one of the involved hair follicles. PMID- 2229533 TI - Subacute cutaneous lupus erythematosus lesions progressing to morphea. AB - A women had annular lesions of subacute cutaneous lupus erythematosus that slowly resolved and were replaced by plaques of morphea. The immunologic implications of this unique transitional case of subacute cutaneous lupus erythematosus to morphea are discussed. PMID- 2229534 TI - Severe lidocaine intoxication by cutaneous absorption. AB - A severe lidocaine intoxication by cutaneous absorption is described. Data are presented to show a significant absorption of lidocaine through diseased skin when lidocaine cream is used as a local anesthetic. Awareness of this route of intoxication might be important in patients in whom neurologic or psychiatric symptoms develop while large amounts of lidocaine cream are being used. PMID- 2229535 TI - Persistent melanocytic lesions associated with cosmetic tanning bed use: "sunbed lentigines". AB - A patient with persistent melanocytic lesions after tanning bed use is described. A review of the literature provides two additional examples of similar clinical and histologic presentations after UVA exposure without psoralen. To our knowledge, this is the first reported case of "sunbed lentigines" in the United States. PMID- 2229536 TI - Miliary tuberculosis presenting as skin lesions in a patient with acquired immunodeficiency syndrome. AB - Acute miliary tuberculosis of the skin is an extremely rare infection that occurs in immunocompromised persons. We report an intravenous drug abuser with human immunodeficiency virus infection in whom erythematous papules developed on the trunk and proximal aspect of the extremities. Visceral lesions of unsuspected miliary tuberculosis were discovered at autopsy, and the cutaneous papules were found to contain Mycobacterium tuberculosis. This is the first reported case of this cutaneous infection in a patient with the acquired immunodeficiency syndrome. PMID- 2229537 TI - Disseminated Kaposi's sarcoma not associated with HIV infection in a bisexual man. AB - We report a 42-year-old white bisexual man with disseminated Kaposi's sarcoma limited to the skin and gastrointestinal tract. Results of several serum tests for human immunodeficiency virus (HIV) antibodies have been negative. The CD4/CD8 ratio has remained normal, and his Kaposi's sarcoma has had a benign clinical course during 30 months of follow-up. Similar reports of disseminated Kaposi's sarcoma with a benign clinical course in homosexual or bisexual men without demonstrable HIV infection are reviewed. Some cellular immune impairment that might be more prevalent in the homosexual population may be implicated in the pathogenesis of this type of Kaposi's sarcoma. PMID- 2229538 TI - Traumatic asphyxia. AB - Traumatic asphyxia is a distinctive clinical syndrome characterized by cervicofacial cyanosis and edema, multiple petechiae, and subconjunctival hemorrhage after a severe crush injury of the thorax or of the upper part of the abdomen. A case of traumatic asphyxia is reported, and its clinical and pathophysiologic features are discussed. PMID- 2229539 TI - Linear porokeratosis: successful treatment with diamond fraise dermabrasion. AB - A patient with linear porokeratosis was successfully treated with diamond fraise dermabrasion. Follow-up evaluation revealed an excellent cosmetic result with adequate repigmentation, no scarring, and no recurrence of lesions. Long-term follow-up will be necessary to determine whether dermabrasion treatment of linear porokeratosis provides adequate prophylaxis against the subsequent development of malignancy. PMID- 2229540 TI - Vulvar melanosis. AB - Vulvar melanosis is a condition in which intensely pigmented irregular macules, clinically mimicking malignant melanoma, appear on the vulva. A biopsy specimen shows only marked lower epidermal pigmentation without any melanocytic atypia or nesting. The process is benign, and reassurance is the only treatment. PMID- 2229541 TI - Giant pilomatrix carcinoma: report and review of the literature. PMID- 2229542 TI - Eruptive seborrheic keratoses in a young woman with acromegaly. AB - The sign of Leser-Trelat, or eruptive seborrheic keratoses, is purported to be a cutaneous marker for many underlying malignancies. Elevation in levels of growth factors has been postulated to be the stimulus for the sudden eruption of multiple new seborrheic keratoses. In support of this hypothesis we present a case of eruptive seborrheic keratoses in a young woman with acromegaly and elevated levels of growth hormone. PMID- 2229543 TI - Neonatal nasopharyngeal hairy polyp: CT and MR appearance. AB - We report a rare tumor of the nasopharynx in the neonate: the teratoid or hairy polyp. In addition to the traditional modes of evaluation (barium swallow, plain radiography, and indirect laryngoscopy), CT and magnetic resonance were used to assess this unusual cause of respiratory distress and vomiting in a newborn. PMID- 2229544 TI - Temporomandibular joint chondrosarcoma: CT demonstration. AB - Chondrosarcoma of the temporomandibular joint is a rare lesion. A 49-year-old woman presented with painless left preauricular swelling. Computed tomography demonstrated a soft tissue mass in the left temporomandibular joint with extraarticular extension along the mandibular ramus. Calcification was present in the extraarticular component. PMID- 2229545 TI - Wegener granulomatosis presenting on CT with atypical bronchovasocentric distribution. PMID- 2229546 TI - CT and MR imaging of partial anomalous pulmonary venous return to the azygos vein. AB - Partial anomalous pulmonary venous return to the azygos vein is very unusual, occurring in 0.02% of autopsy examinations. We report the CT, magnetic resonance, and angiographic findings in a 67-year-old man with partial anomalous venous return to the azygos vein. PMID- 2229547 TI - CT monitoring of therapy for meconium ileus. AB - Meconium ileus equivalent is a common complication of cystic fibrosis in the postneonatal period. Because of the added risks of surgery in these patients, conservative management is preferred. We describe here a method of monitoring the conservative treatment of this condition using CT and suggest that its application will reduce the need for potentially dangerous surgical intervention. PMID- 2229548 TI - CT evaluation of atypical hepatic fatty metamorphosis. AB - Focal fatty metamorphosis of the liver is a well-recognized entity characteristically demonstrated by a nonspherical, low-density area without mass effect. We present a case of focal fatty metamorphosis of the liver that shows multiple areas of low attenuation within the liver with mass effect. Radionuclide liver-spleen scan shows multiple focal defects corresponding to the areas of fatty metamorphosis. PMID- 2229549 TI - Ciliated hepatic foregut cyst with solid tumor appearance on CT. AB - We report a patient with a rare cystic hepatic tumor that was demonstrated as a high density mass by unenhanced CT and as a cystic mass with high echoic spots by ultrasonography. At surgery, the tumor was a unilocular cyst containing viscid tan fluid. Histopathologically, it was lined by ciliated epithelium and diagnosed as ciliated hepatic foregut cyst. We discuss the correlation between radiological imaging and content of the cyst. PMID- 2229550 TI - Central dot sign on CT of liver cysts. AB - The central dot sign on CT in Caroli disease has been described previously. We describe a patient with the central dot sign who had periductal cysts but did not have Caroli disease. PMID- 2229551 TI - Pelvic mucocele following colostomy: CT and ultrasound findings. AB - Mucocele formation is a rare complication of colorectal surgery. We present a case of a mucocele following colostomy and mucosal proctectomy for fecal incontinence. The pathophysiologic and radiologic features are similar to those of mucocele of the appendix. PMID- 2229552 TI - Computed tomography of chronic nonpuerperal uterine inversion. AB - Uterine inversion is an unusual entity; chronic nonpuerperal inversion is rare. In this report we present a case of chronic nonpuerperal uterine inversion that was initially diagnosed as invasive endometrial carcinoma. The CT findings in this case are presented. PMID- 2229553 TI - Psoas muscle calcification and acute renal failure associated with nontraumatic rhabdomyolysis: CT features. AB - We present a case of reversible psoas muscle calcification associated with acute renal failure and alcohol intoxication. The CT demonstration of calcification led to the recognition of rhabdomyolysis. PMID- 2229554 TI - MR demonstration of intraosseous beta-2-microglobulin amyloidosis. AB - We present a case of intraosseous beta-2-microglobulin amyloidosis of a patient receiving long-term hemodialysis. Magnetic resonance imaging clearly demonstrated intraosseous amyloid deposits as hypointense masses in the femoral head. PMID- 2229555 TI - Meniscofemoral ligament simulating tear of the lateral meniscus: MR features. AB - The meniscofemoral ligament can simulate pathology on magnetic resonance images. It can be mistaken for a free osteochondral fragment on sagittal images. A less common pitfall is the simulation of a tear of the posterior horn of the lateral meniscus. A case demonstrating this meniscal pseudotear is presented. PMID- 2229556 TI - Rheumatoid iliopsoas bursitis: MR findings. PMID- 2229557 TI - Three-dimensional segmentation of MR images of the head using probability and connectivity. AB - We describe a three-dimensional (3D) segmentation method that comprises (a) user interactive identification of tissue classes; (b) calculation of a probability distribution for each tissue; (c) creation of a feature map of the most probable tissues; (d) 3D segmentation of the magnetic resonance (MR) data; (e) smoothing of the segmented data; (f) extraction of surfaces of interest with connectivity; (g) generation of surfaces; and (h) rendering of multiple surfaces to plan surgery. Patients with normal head anatomy and with abnormalities such as multiple sclerosis lesions and brain tumors were scanned with a 1.5 T MR system using a two echo contiguous (interleaved), multislice pulse sequence that provides both proton density and T2-weighted contrast. After the user identified the tissues, the 3D data were automatically segmented into background, facial tissue, brain matter, CSF, and lesions. Surfaces of the face, brain, lateral ventricles, tumors, and multiple sclerosis lesions are displayed using color coding and gradient shading. Color improves the visualization of segmented tissues, while gradient shading enhances the perception of depth. Manipulation of the 3D model on a workstation aids surgical planning. Sulci and gyri stand out, thus aiding functional mapping of the brain surface. PMID- 2229558 TI - Laser projection system for radiotherapy and CT-guided biopsy. AB - We devised a laser projection system combined with a CT scanner and radiotherapy treatment planning computer (CT stimulator). The irradiation field can be projected over a range of 180 degrees on the skin of a patient lying on the CT couch. For CT-guided biopsy, the system can project the skin entry point and needle direction. PMID- 2229559 TI - Normal and abnormal white matter tracts shown by MR imaging using directional diffusion weighted sequences. AB - A pulsed magnetic field gradient spin echo technique was used to study the brain of two volunteers and eight patients. The pulsed gradients were applied both perpendicular and parallel to the image slice. Striking changes in signal intensity were demonstrated in white matter depending on the direction in which pulsed gradients were applied. These effects enabled specific white matter tracts to be identified depending on the direction of their fibres. Abnormalities were also demonstrated in these tracts in patients with a variety of diseases, including cases where only minor abnormalities were seen with conventional, highly T2-weighted sequences. The effects were attributed to anisotropically restricted diffusion within white matter. The technique may have application in a wide range of neurological disease and result in better localisation of lesions and improved detection of disease. PMID- 2229560 TI - Three-dimensional time-of-flight MR angiography in the evaluation of cerebral aneurysms. AB - We review our preliminary experience with the use of three-dimensional (3D) time of-flight (TOF) magnetic resonance (MR) angiography (MRA) in the assessment of intra- and extracranial aneurysms. Six patients were examined: Five had intracranial aneurysms and one had a cervical carotid pseudoaneurysm. A 3D rephased gradient recalled echo pulse sequence and maximum intensity projection (MIP) reconstruction algorithm were used. Magnetic resonance angiography, spin echo MR, and conventional angiography were retrospectively reviewed with specific regard to individual vessel visualization, aneurysm depiction, and presence of artifact related to acquisition techniques or MIP reconstruction. All aneurysms were detected on MRA, and anatomical correlation with conventional angiography was excellent. Significant problems included loss of visualization of small vessels, intraluminal signal loss in large vessels, subacute thrombus simulating flow on MIP reconstructions, and limited projections obtainable with MIP techniques. Adequate MRA assessment of aneurysms can be obtained using a combination of T1-weighted spin echo images and 3D TOF MRA. Review of all components of the MRA is required. MRA may be useful in screening asymptomatic patients for intracranial aneurysms as well as in the follow-up of patients treated with balloon occlusion. PMID- 2229561 TI - Proton MR spectroscopy and imaging of the brain in AIDS: evidence of neuronal loss in regions that appear normal with imaging. AB - Central nervous system involvement is increasingly being recognised as a common manifestation of the acquired immunodeficiency syndrome (AIDS), either as a direct effect of the human immunodeficiency virus, or as a result of secondary infection or malignancy. A subset of patients with clinical or psychometric evidence of CNS involvement have normal appearances on imaging. This report describes proton magnetic resonance spectroscopy (1H MRS) in two patients with AIDS and discusses the role of 1H MRS in providing a marker of neuronal loss in patients with normal or borderline imaging. PMID- 2229562 TI - Proton MR spectroscopy of the brain in infants. AB - Proton magnetic resonance spectroscopy (MRS) was used to study the brain of 2 normal and 15 abnormal infants aged from 33 weeks postmenstrual age (PMA) to 14 months postnatal age. Eleven of the infants were examined on at least two occasions. The principal clinical diagnoses in the abnormal infants were perinatal ischemic and hemorrhagic brain injury. All proton spectra demonstrated peaks that were assigned to N-acetylaspartate (NAA), choline containing compounds (Cho), and creatine plus phosphocreatine (Cr). The NAA/Cho and NAA/Cr ratios increased with age, while the Cho/Cr ratio decreased with age in the majority of infants. The NAA/Cho ratio was generally lower in abnormal infants, but the difference was not apparent before 40 weeks (PMA). This ratio was lowest in infants with the severest degree of neurological abnormality. Proton and phosphorus MRS was compared in seven infants. In those with severe brain lesions, early phosphorus spectra were abnormal. On follow-up the phosphorus spectra became normal, but the proton spectra showed persistently low NAA/Cho and NAA/Cr ratios. Proton MRS provides new information that may be complementary to phosphorus MRS in the diagnosis and monitoring of brain development in normal and neurologically damaged infants. PMID- 2229563 TI - MR imaging of vertebrobasilar vascular disease. AB - Sixteen patients with vascular lesions of the vertebral and basilar arteries were studied with magnetic resonance imaging. The vascular abnormalities included seven cases of atherosclerotic disease with partial or complete thrombosis, six aneurysms, two cases of vertebrobasilar dolichoectasia, and one basilar artery dissection. Magnetic resonance effectively demonstrated vascular thrombosis with occlusion as high signal intensity on spin echo (SE) sequences with absence of flow void and no flow enhancement on gradient echo (GRE) images. Nonthrombosed aneurysms exhibited mixed signal intensity on SE images and hyperintensity on GRE images. Intraluminal thrombus also appeared heterogeneous, with variable signal intensity depending on the specific components of hemorrhage present. Correlation of the SE and GRE scans was helpful for distinguishing stasis and turbulent flow from thrombus. Compression of cranial nerves by vascular structures was clearly depicted in both cases of dolichoectasia. Basilar artery dissection was displayed as a focal area of flow void surrounded by a thrombosed false lumen. Magnetic resonance is an effective noninvasive method for evaluating vascular pathology of the vertebrobasilar system. PMID- 2229564 TI - White matter hyperintensities may correspond to areas of increased blood volume: correlative MR and PET observations. AB - A method for correlating positron emission tomography with magnetic resonance (MR) imaging enabled the authors to examine the high intensity white matter areas in T2-weighted images in patients with internal carotid artery occlusion. The high intensity areas showed increased cerebral blood volume compared with the ipsilateral and contralateral normal intensity white matter. This observation may have relevance in explaining some of the patchy white matter lesions seen in MR images. PMID- 2229565 TI - MR of cord transection. AB - Spinal cord transection following breech or difficult cephalic deliveries has been well described. It is important to be aware that spinal cord transection in children may occur following severe trauma such as motor vehicle accidents often without evidence of underlying skeletal injury. We report three pediatric cases, one of which showed no evidence of underlying skeletal injury and two where the level of cord transection was below and remote from the site of a cervical fracture. When a neurologic deficit does not correlate with a known bony or ligamentous level of injury or is present despite normal routine plain radiographs, further imaging is warranted to exclude a remote cord transection as demonstrated in our patients. PMID- 2229566 TI - Case of anaphylaxis and four cases of allergic reaction following Gd-DTPA administration. AB - Although Gd-diethylenetriamine pentaacetic acid (Gd-DTPA) is considered to be safe and well tolerated by patients, we have seen adverse reactions in 5 of 344 cases. This paper reports those five cases of reactions to intravenous Gd-DTPA injection. PMID- 2229567 TI - Cholesterol granuloma of the frontal bone: CT diagnosis. AB - Cholesterol granuloma of the frontal bone is a distinct clinical entity. This expanding lesion grows slowly within the diploe of the frontal bone until it extends into the orbit and causes globe displacement. We report the clinical and the CT findings in 11 patients with cholesterol granuloma of the orbit. The CT characteristics of cholesterol granuloma of the frontal bone appear to enable a correct preoperative diagnosis. PMID- 2229568 TI - Pulmonary arteriovenous malformations: diagnosis by gradient-refocused MR imaging. AB - Six known or suspected pulmonary arteriovenous malformations (AVMs) in four patients were evaluated with magnetic resonance (MR) imaging at 1.5 T. All lesions were imaged using a gradient-refocused echo pulse sequence with a 25/13 ms [repetition (TR)/echo (TE) times] and a 30 degrees flip angle, as well as with a cardiac-gated spin echo short TR/TE pulse sequence technique. Five of the lesions were vascular in nature based on their signal intensity characteristics, and one nonvascular lesion was a carcinoid tumor. On the spin echo images, the AVMs showed a central signal intensity void with a peripheral rim of intermediate signal intensity that was detectable for lesions greater than or equal to 1.5 cm in size. Smaller lesions were more difficult to distinguish from the surrounding air-filled lung, which normally generates no appreciable signal on MR images. The AVMs demonstrated uniform high signal intensity on the gradient echo pulse sequence and were more conspicuous, irrespective of size. With a single breath hold scan, the vascular nature of the lesion could be rapidly confirmed with an acquisition time of 13 s. In three patients, the cine MR gradient echo images showed a pulsatile quality to the signal intensity in the lesion over the cardiac cycle similar to that within adjacent pulmonary vessels. The results of this study show a potential role for gradient echo MR imaging as a rapid, noninvasive method to evaluate the vascular nature of an atypical pulmonary nodule. PMID- 2229569 TI - Staphylococcal mediastinitis due to sternoclavicular pyarthrosis: CT appearance. AB - Three cases of acute mediastinitis secondary to staphylococcal sternoclavicular pyarthrosis are reported. In each case, the patient presented with minimal signs and symptoms and mediastinitis was not suspected until demonstrated by preoperative CT. Since septic arthritis of the sternoclavicular joint may be insidious in onset and is associated with a high incidence of life-threatening secondary mediastinitis, CT is recommended as the initial imaging study in the evaluation of unexplained sternoclavicular joint pain and swelling. PMID- 2229570 TI - MR evaluation of chest wall involvement in malignant lymphoma. AB - Chest CT and magnetic resonance (MR) examinations of 28 patients with newly diagnosed or recurrent lymphoma involving the mediastinum were retrospectively evaluated for evidence of chest wall involvement. Computed tomography demonstrated seven sites of chest wall involvement in four patients; whereas MR demonstrated 14 sites in seven patients, including all sites shown by CT. Eight chest wall lesions were located in the extranodal soft tissues (three sites were contiguous with anterior mediastinal lymphadenopathy; three sites were contiguous with pleural/parenchymal disease; and one each involved the breast and multiple vertebral bodies). Six sites involved lymph nodes in the interpectoral (n = 4), submammary (n = 1), and infraspinatus (n = 1) areas. Lesion conspicuity in the chest wall was better on T2- than T1-weighted sequences and was best on short inversion time inversion recovery. Detection of chest wall lymphoma may alter staging; when present in this group of patients, it influenced management in two of the seven patients. PMID- 2229571 TI - Computed tomography of renal lymphoma. AB - The CT studies of 29 patients with renal or perirenal lymphoma were retrospectively reviewed. Four patterns of disease were identified. Seventeen of 29 patients (59%) had bilateral renal masses. Only seven of these patients had associated enlarged retroperitoneal lymph nodes. Eight patients (28%) had single renal or perirenal lesions adjacent to or contiguous with bulky retroperitoneal lymphadenopathy. Three patients had infiltration of the perirenal space without significant renal parenchymal involvement, and one patient had a solitary renal mass. No patients in this series had diffuse involvement of the kidney without a focal mass. Renal involvement with lymphoma should be considered in any patient who develops multiple homogeneous solid renal or perirenal masses, even in the absence of other retroperitoneal disease. PMID- 2229572 TI - Gadolinium-DOTA enhanced MR imaging of adnexal tumors. AB - We conducted a retrospective study to assess the potential of contrast enhanced magnetic resonance (MR) imaging in evaluating adnexal tumors. Sixty patients with a total of 77 pelvic lesions underwent MR imaging at 1.5 T and transabdominal ultrasound (US). Precontrast T1- and T2-weighted and Gd-DOTA enhanced T1-weighted MR images were obtained. Diagnoses were proved by surgery in 57 patients. Of the 77 lesions, 54 masses were of ovarian origin, including 12 malignant disorders. Ultrasound demonstrated the lesions in 92%, whereas the sensitivity of unenhanced T2-weighted and postcontrast MR images was 98 and 96%, respectively. Compared to the T2-weighted images, postcontrast MR imaging showed superior overall tumor delineation, assessment of intratumoral architecture, and definition of tumor origin. Contrast enhancement of tumors did not differ significantly between normal ovary and benign and malignant lesions. All modalities were unable to predict malignancy of complex lesions. Based on our study, US remains the screening modality of choice in the evaluation of adnexal tumors. Contrast enhanced MR imaging may be valuable for assessing complex lesions or when the origin of the mass cannot be determined by US. Using contrast enhanced T1 weighted images instead of T2-weighted images may lead to a significant reduction in acquisition time. PMID- 2229573 TI - Impending rupture of nonaneurysmal bacterial aortitis: CT diagnosis. AB - The CT appearance of mycotic abdominal aortic aneurysms leading to eventual rupture has been well described. On the other hand, ruptured nonaneurysmal bacterial aortitis has not been demonstrated in the CT literature. We present two cases with subsequent rupture documented on CT. The characteristic findings of periaortic density and adjacent gas collection should suggest the diagnosis of acute aortic infection. This may herald impending rupture, even in the absence of aneurysmal dilatation, and should direct therapy accordingly. PMID- 2229574 TI - Proton chemical shift imaging of bone marrow for monitoring therapy in leukemia. AB - In three patients with different forms of leukemia, follow-up examinations before, during, and after chemotherapy and bone marrow transplantation were performed by proton chemical shift imaging (1H-CSI). The relative fat and water fractions were computed in representative regions of the marrow in the femur, pelvis, and lumbar spine. On serial examinations the fat fractions increased over time, in agreement with the responses to therapy proven by bone marrow biopsies from the iliac crest. These preliminary results suggest a role for magnetic resonance and CSI in the monitoring of therapy in leukemia and systemic neoplastic diseases. PMID- 2229575 TI - Grading liposarcomas with PET using [18F]FDG. AB - Five patients with liposarcomas of the thigh were studied using positron emission tomography (PET) with [18F]2-deoxy-2-fluoroglucose (FDG). There were three low grade tumors (all National Cancer Institute Grade 1 myxoid liposarcomas) and two high-grade tumors (both pleomorphic liposarcomas, Grades 2 and 3). The low-grade liposarcomas were easily identified with an average dose uptake ratio (DUR) of 1.38 +/- 0.045 (mean +/- SD). The high-grade lesions were more avid for FDG with a mean DUR of 2.45 +/- 0.24. There was a significant difference (p = 0.004) in the DUR for the two groups and the histological grade of malignancy was highly correlated with the DUR for FDG (Rho = 0.89). These findings suggest that FDG-PET may be useful for distinguishing between low-grade and high-grade liposarcomas. PMID- 2229576 TI - MR evaluation of triangular fibrocartilage complex tears in the wrist: comparison with arthrography and arthroscopy. AB - To evaluate the accuracy of magnetic resonance (MR) in the detection of tears of the triangular fibrocartilage complex (TFCC), 10 consecutive patients with posttraumatic chronic wrist pain were examined with MR, arthrography, and arthroscopy and the results were compared. The MR images of 16 control subjects were also examined to define the MR appearance of the normal TFCC. When compared with arthroscopic findings, both MR and arthrography had two false-negative results (sensitivity, 80%) and no false-positive results. Regarding the sites of the TFCC tears, the findings on MR did not always correlate with the findings on arthrography. In no case was MR able to visualize the cartilaginous lesions visible by arthroscopy. These preliminary results illustrate the ability of MR to assess the integrity of the TFCC and suggest its use as the first imaging technique following plain radiography in the evaluation of patients with chronic posttraumatic pain on the ulnar side of the wrist. PMID- 2229577 TI - MR patterns of dialysis arthropathy. AB - Ten patients (average age 51 years) on long-term hemodialysis (average duration 13.5 years) were examined by magnetic resonance (MR) (all cases) and CT (five cases) for cystic radiolucencies of the wrist, shoulders, and hips. MR and CT revealed more lesions of smaller size than plain films and both showed a constant communication with the joint space. Synovial hypertrophy was generally absent or very mild even in the case of large osseous erosions. The MR analysis of the content of the lesions in the wrist was quite variable: low signal on T1- and T2 weighted images (12 of 24), low signal on T1- and high signal on T2-weighted images (10 of 24), and high signal on T1- and T2-weighted images (2 of 24). The patterns of transplanted (four cases) or ungrafted (six cases) patients were indistinguishable. These results suggest an articular origin of the lesions, but different from synovial processes such as rheumatoid arthritis, and confirm their probable multifactorial pathogenesis. PMID- 2229578 TI - The "notch" sign: meniscal contour deformities as indicators of tear in MR imaging of the knee. AB - Conventional magnetic resonance (MR) criteria for meniscal tearing emphasize intrameniscal signal and its communication with the articular surface. In this retrospective study, the value of a focal contour deformity of the meniscal articular surface, termed a "notch," as an additional MR sign of meniscal tearing was assessed. One hundred fifty-four menisci were evaluated. Twenty-three of 24 notches correlated with the site of tear at arthroscopy. Seven notches improved the reading confidence from possible to definite tear; in eight notches, the diagnosis of tear would otherwise not have been considered. Five tears occurred without intrameniscal signal, four following recent trauma. The notch sign improved the sensitivity from 79.8 to 87.8%. Notches are useful additional signs of meniscal tearing, increasing the confidence of a reading when occurring near grade 1 or 2 meniscal signal, and are the only MR sign present in some tears. PMID- 2229579 TI - Cranial MR imaging in hypomelanosis of Ito. AB - Hypomelanosis of Ito (HI) is a rare neurocutaneous syndrome frequently associated with neurologic abnormalities. Approximately 95 cases have been reported in the literature. Intracranial findings demonstrated by magnetic resonance imaging in a patient with HI include hemimegalencephaly, abnormal white matter signal, and small discrete bilateral periventricular cysts. No gray matter heterotopias or other migrational abnormalities were identified. Periventricular cystic lesions have not been described previously in this condition. PMID- 2229580 TI - Lhermitte-Duclos disease: CT and MR findings. AB - The typical CT findings of Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum) are a hypodense nonenhancing unilateral posterior fossa mass, with or without adjacent occipital thinning, hydrocephalus, and calcification. Magnetic resonance (MR) has been found to be very helpful, and superior to CT, in delineating the margins of the lesion for determining the extent of surgical resection. Since recurrence is known, MR is important in the follow-up of these patients. To our knowledge this is the first reported case that included MR examination with administration of gadolinium. There was no enhancement of the lesion, consistent with previous reports of no contrast enhancement on CT. PMID- 2229581 TI - MR imaging of spinal pachymeningitis. AB - We report a case with pathologic correlation that demonstrates the magnetic resonance imaging characteristics of spinal pachymeningitis. Contrast enhanced T1 weighted images clearly demonstrated the thickened contrast enhancing meninges in a patient with progressive radiculomyelopathy who had both clinical and imaging evidence of progression of disease. PMID- 2229582 TI - MR findings in a patient with Ramsay-Hunt syndrome. AB - A case of Ramsay Hunt syndrome (herpes zoster oticus) was studied with Gd diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging using a surface coil rather than a conventional head coil. This allowed us to demonstrate in detail the inflammatory changes of the multiple structures, involved. PMID- 2229583 TI - Estimation of maxillary alveolar cleft volume by three-dimensional CT. AB - Reconstruction of cleft lip and palate deformities is a challenging problem involving a variety of the subspecialties of surgery, dentistry, and medicine as well as radiology. This paper outlines the contribution of three-dimensional CT to preoperative treatment planning for bone grafting of a maxillary cleft alveolus. PMID- 2229584 TI - Nasopharyngeal melanotic melanoma: MR characteristics. AB - This report presents a rare case of nasopharyngeal melanoma with maxillary sinus extension and lymph node metastasis. The unusual magnetic resonance signal features and the differential diagnosis are discussed. PMID- 2229585 TI - Effects of florfenicol, chloramphenicol, and thiamphenicol on phagocytosis, chemiluminescence, and morphology of bovine polymorphonuclear neutrophil leukocytes. AB - Florfenicol, chloramphenicol, and thiamphenicol were tested in vitro to determine their potential toxic effects on bovine neutrophils. Antibiotics were tested at 4000, 2000, and 10 micrograms/ml of incubation mixture. Percentage phagocytosis was determined by incubations with neutrophils isolated from milk of five cows and 32P-labeled Staphylococcus aureus and 5% skim milk. The effect of 4000 micrograms of each antibiotic on chemiluminescence was determined on neutrophils isolated from mammary secretions of three nulliparous heifers. Morphological evaluation by transmission and scanning electron microscopy was performed on neutrophils isolated from two heifers at antibiotic concentrations of 4000 and 10 micrograms/ml. Chloramphenicol depressed phagocytosis at the high and medium doses and blocked chemiluminescence activity at the high dose. No effects were observed for florfenicol and thiamphenicol. Transmission electron microscopic examination showed that at the high concentration of drugs, 99, 99, 97, and 76% of the neutrophils treated with florfenicol, chloramphenicol, thiamphenicol, and dimethyl sulfoxide were abnormal. Examination by scanning electron microscopy showed that the percentage of neutrophils without pseudopodia averaged 67, 94, 32, and 16%, respectively. Results indicated that neither florfenicol nor thiamphenicol altered neutrophil function, but they did alter neutrophil morphology, although to a lesser extent than did chloramphenicol. PMID- 2229586 TI - Total and differential somatic cell counts and N-acetyl-beta-D-glucosaminidase activity in mammary secretions during dry period. AB - Eighteen Holstein cows free of intramammary infection were sampled during dry period to measure changes in total SCC, differential cell counts, and N-acetyl beta-D-glucosaminidase activity of milk or dry secretion. The design was to sample prior to and at drying off, two or more times during wk 1 of dry period, at 14 and 21 d of dry period, and after calving; 7 cows were sampled rotationally by quarters at 7, 14, and 21 d to avoid altering normal processes by repeated sampling. Total SCC of secretions declined just after drying off, increased to a peak of 6.593 (log10 scale) at 2 wk, and then declined slightly at 3 wk. Percentage of neutrophils rose from 33.3 at drying off to 83.8 at 1 wk and declined to 59.2 at 3 wk. Lymphocyte percentage declined in wk 1 of dry period but increased during wk 2 and 3. Activity of N-acetyl-beta-D-glucosaminidase in secretion rose throughout the first 3 wk of dry period. PMID- 2229587 TI - Bacterial counts associated with recycled newspaper bedding. AB - Bacterial counts associated with recycled newspaper, wood shavings, and pelleted corn cobs used as bedding for lactating dairy cows were compared. Chopped newspaper and pelleted corn cobs had similar gram-negative bacterial, coliform, and streptococcal bedding counts. Staphylococcal counts in pelleted corn cobs were greater than in chopped newspaper. Conversely, gram-negative bacterial, coliform, and staphylococcal counts in chopped newspaper were greater than in wood shavings. Coliform and streptococcal counts did not differ between chopped newspaper and wood shavings bedding materials. Teat swab counts from cows bedded on pelleted corn cobs were greater than those from cows bedded on chopped newspaper for gram-negative bacterial, coliform, Klebsiella species, and staphylococci. Streptococcal teat swab counts did not differ between cows bedded on chopped newspaper and pelleted corn cobs. Cows bedded on chopped newspaper and wood shavings had similar gram-negative bacterial, coliform, and Klebsiella species teat swab counts. Streptococcal and staphylococcal teat swab counts were greater from cows bedded on chopped newspaper than those from cows bedded on wood shavings. Teat swab and bedding counts were correlated. In general, bacterial counts in bedding suggest no advantage in using chopped newspaper over pelleted corn cobs or wood shavings in reducing exposure of teats to environmental mastitis pathogens. PMID- 2229588 TI - Sodium intake by pregnant cows and plasma aldosterone and cortisol concentrations in the fetus during late pregnancy. AB - The purpose of this study was to evaluate the influence of maternal dietary Na intake on the plasma concentrations of aldosterone and cortisol in cows and their fetuses during late pregnancy. Seven cows received a diet with normal amounts of Na (25 g Na per cow/d) and seven others an Na-loaded diet (210 g Na per cow/d) during the last 40 d of gestation. Maternal and fetal blood samples were collected regularly during the last month of gestation through jugular vein puncture and cotyledonary artery indwelling catheters. Serum Na and K concentrations and plasma osmolalities increased, but concentrations of aldosterone decreased in maternal and fetal plasma when cows were fed the Na loaded diet. Diets did not modify concentrations of cortisol in maternal and fetal plasma. Thus, an increase in Na intake by dams influenced concentration of Na and K in fetal plasma and fetal adrenal secretion of aldosterone. PMID- 2229589 TI - Double insemination and gonadotropin-releasing hormone treatment of repeat breeding dairy cattle. AB - Our objective was to determine if double inseminations during the same estrous period of dairy cattle eligible for their third or fourth service (repeat breeders) would improve pregnancy rates equivalent to injections of GnRH given at the time of AI. Repeat-breeding, lactating cows from six herds (five herds in the San Joaquin Valley of central California and one herd in northeast Kansas) were assigned randomly to four treatment groups when detected in estrus: 1) single AI plus no injection, 2) single AI plus 100 micrograms GnRH at AI, 3) double AI plus no injection, or 4) double AI plus 100 micrograms of GnRH at AI. Inseminations were performed according to the a.m.-p.m. rule. The second AI for the double AI treatment was given 12 to 16 h after the first AI. Injections of GnRH were given intramuscularly immediately following the single AI or the first AI of the double AI. Pregnancy rates of cows given a single AI and hormone injection were numerically higher in all six herds than those of their herdmates given only a single AI. In five of six herds, the pregnancy rates of cows given a double AI and hormone injection were numerically higher than pregnancy rates of their herdmates given only a double AI. Overall pregnancy rates for the four treatments were 1) 112/353 (32.1%), 2) 165/406 (41.6%), 3) 119/364 (33.5%), and 4) 135/359 (37.5%). Gonadotropin-releasing hormone increased pregnancy rates of repeat breeders compared with controls given only a single AI. No further benefit beyond the single AI was accrued from the double AI treatment, with or without concurrent hormone administration. PMID- 2229590 TI - Effects of androgenizing dairy heifers with ear implants containing testosterone and estrogen on detection of estrus. AB - Lactating dairy cows in four lots were observed for sexual behavior for 6 mo. One freemartin heifer in each lot was implanted with testosterone propionate and estradiol benzoate to aid in detection of estrus. Blood samples were obtained from androgenized heifers every other week for determination of serum testosterone. The addition of an androgenized heifer to each lot increased the number of mounts and attempts to mount cows, both overall and within observation periods. Thus, the likelihood of detecting a cow in estrus was increased with the addition of the androgenized heifers. Greatest benefit was seen when one or two cows were simultaneously in estrus in each lot. Observational data and serum progesterone concentration of mounted cows indicated that androgenized heifers were selectively mounting open cows displaying estrus, whereas the remaining nonandrogenized cows were less selective with their mounting activity. Serum testosterone increased after heifers were implanted, but testosterone was not related to the proportion of sexual activity. Duration of sexual activity by the implanted heifers was approximately 90 d. PMID- 2229591 TI - Nonreturn rates of dairy cattle following uterine body or cornual insemination. AB - In the dairy cattle industry, uncertainty still remains regarding the most desirable site of inseminate deposition to maximize AI conception rates. The effect of site of inseminate deposition on nonreturn rates was determined from 2195 cornual and 2428 uterine body-bred dairy cattle. Twelve technicians from various areas of Pennsylvania and New York were chosen on the basis of their accuracy of semen deposition in retraining sessions, average nonreturn rates, and their willingness to cooperate in the study. For a 3-mo period (June, July, and August 1988), technicians alternated weeks of cornual and uterine breeding on all dairy cattle inseminated. One-half (.25 ml) of each semen unit was deposited approximately 5.1 cm into each uterine horn for cornual insemination. No significant difference in nonreturn rates was found between horn-bred (70.8%) and body-bred (69.5%) cows. The range of differences in percent nonreturn rates for technicians was 19 and 30% for body and cornual inseminations, respectively. A significant difference in nonreturn rates was found between technicians and between months with significantly higher average nonreturn rates (6.8%) in June. Cornual and uterine body deposition of semen yielded similar results; therefore, depositing an inseminate in the uterine horns to maximize fertility is unnecessary. PMID- 2229592 TI - Dissociation of calcium soaps of long-chain fatty acids in rumen fluid. AB - Dissociation of 5% solutions of calcium soaps of soya, tallow, stearic acid, and palm fatty acid distillate was studied by titration with 1 N HCl. Release of calcium ions was directly correlated with decrease in pH value. Estimated pKa values were 5.6, 4.6, 4.5, and 4.5 for calcium soaps of soya, palm fatty acid distillate, tallow, and stearic acid, respectively. Dissociation of 5% solutions in acetate buffer at pH values of 5.0, 5.5, 6.0, and 6.5 was measured in terms of release of soluble calcium. Dissociation was maximum at pH 5.0, minimum at pH 6.5, and dependent on unsaturation of fatty acids in the soaps. Soluble calcium in the acetate-buffered rumen fluid was higher than predicted from pKa of calcium soaps, due to formation of soluble calcium acetate; however, the relative patterns were similar to their pKa values. Unsaturated soaps are less satisfactory for maintaining normal rumen function, because dissociation is relatively higher. Calcium soaps of palm fatty acid distillate were satisfactorily stable to pH 5.5. PMID- 2229593 TI - Effects of feeding fungal culture extract and animal-vegetable fat on degradation of hemicellulose and on ruminal bacterial growth in heifers. AB - Four Holstein heifers cannulated in the rumen and proximal duodenum were used to analyze effects of Aspergillus oryzae fermentation extract and yeast culture (Amaferm Micro-Mix. Biozyme Enterprises, Inc., St. Joseph, MO) and 5% animal vegetable fat on ruminal and total tract digestibilities of nutrients. Heifers were assigned treatments in a 4 x 4 Latin square design with a 2 x 2 factorial arrangement of treatments. Few interactions between main effects were noted. Feeding fat decreased ruminal molar ratio of acetate:propionate. Rate of disappearance of potentially digestible NDF from orchardgrass hay was higher when heifers were fed fat. Thus, the lack of differences in digestibilities of NDF, ADF, or in the major hemicellulosic sugars is interpreted to suggest that 5% animal-vegetable fat had few toxic effects on ruminal microbes under the conditions of this study. Amaferm Micro-Mix tended to increase acetate:propionate in the rumen, but had little effect on site or extent of digestion of any of the fiber components measured. Efficiency of bacterial protein synthesis was not affected by treatment. Ruminal and total tract digestibilities of total hemicellulosic sugars were highly correlated (r = .82 and .72) with respective digestibilities of hemicellulose measured as NDF minus ADF. PMID- 2229594 TI - Influence of decoquinate fed to neonatal dairy calves on early and conventional weaning systems. AB - Forty-four Holstein calves were assigned randomly to treatments in a 2 x 2 factorial arrangement of weaning age (4 or 7 wk) and coccidiostat (treatment or control). The objective of this study was to compare the effectiveness of a coccidiostat, decoquinate, on health parameters and growth of neonatal dairy calves on early and conventional weaning systems. Calves weaned at 4 wk had greater intakes of grain in wk 5 to 7 than did calves weaned at 7 wk. Differences in intakes between weaning groups were not apparent from wk 8 to 24. Fecal coccidia oocyst counts were not affected by age at weaning but were affected by coccidiostat feeding at the rate of .5 mg/kg BW/d offered from 3 d of age and throughout the trial. No effects due to age at weaning or coccidiostat treatment were found in plasma glucose, urea N, and minerals (Ca, P, Na, Cl, K, Mg). Growth parameters were significantly increased in treated animals. Total BW was increased (wk 9 to 24) in treated over control calves (127.3 versus 118.5 kg). Height at withers was also increased in treated calves (95.0 vs. 92.8 cm). Coccidiosis treatment increased growth of dairy calves from 9 to 24 wk, but no interactions were found between coccidiosis treatment and age at weaning. PMID- 2229595 TI - Effects of feeding frequency on ruminal parameters, plasma insulin, milk yield, and milk composition in Holstein cows. AB - Two experiments were conducted to determine the effects of frequency of feeding on ruminal fermentation, blood parameters, milk yield, and milk composition in cows fed a 60% pelleted concentrate and 40% chopped alfalfa hay (DM basis) diet. In Experiment 1, four ruminally cannulated cows were fed concentrates in 12 equal portions at 2-h intervals or in two equal portions at 0500 and 1500 h in a crossover design. In Experiment 2, treatments were as in Experiment 1 plus an additional treatment consisting of a total mixed diet fed at 2-h intervals in a 3 x 3 Latin square design. All treatment periods were 2 wk. In Experiment 1, increased frequency of concentrate feeding tended to result in elevated ruminal pH and increased acetate to propionate ratio. Plasma insulin concentration tended to be higher (1.54 vs. 1.04 ng/ml) and milk fat percentage increased from 2.21 to 2.60% for 2 and 12 times daily feeding, respectively. In Experiment 2, frequency of feeding concentrate or total mixed diet did not affect ruminal and blood parameters or milk yield. In both experiments, milk protein and lactose concentrations were not influenced by feeding frequency. Results suggest that where intake is kept constant, increased feeding frequency will not influence milk yield but could result in elevated milk fat percent in animals fed fat depressing diets. PMID- 2229596 TI - Stochastic modeling of multiple ovulation and embryo transfer breeding schemes in small closed dairy cattle populations. AB - Genetic changes and genetic drift in three small closed dairy cattle populations were examined with a stochastic simulation model. Multiple ovulation and embryo transfer and AI techniques were simulated in three populations, two with 88 breeding females each and one with 352 breeding females. The selection goal was to maximize genetic improvement in milk yield. The reduction in genetic variation due to inbreeding and linkage disequilibrium was accounted for in the simulation. Strict restriction against inbred mating slowed genetic progress significantly in the small population but would not be consequential in the larger population. However, allowing inbred mating in the smaller population caused a rapid accumulation of inbreeding. Linkage disequilibrium was as important as inbreeding in reducing genetic variation. Genetic drift variance was much smaller in the larger population. PMID- 2229597 TI - Effect of sialoadenectomy on the ability of mouse serum to induce deoxyribonucleic acid synthesis in mammary epithelial cells: possible role of epidermal growth factor. AB - Serum was collected from sham-operated or sialoadenectomized mice and added to serum starved cultures of normal mouse mammary epithelial cells. Synthesis of DNA, estimated with a pulse of 1 microCi/ml [3H]thymidine between 17 and 18 h after adding serum, was increased by serum. Sialoadenectomy did not affect the ability of low serum concentrations (less than 4%) to increase DNA synthesis, but DNA synthesis induced by higher serum concentrations was reduced by sialoadenectomy. Physiological concentrations of epidermal growth factor restored the ability of serum from sialoadenectomized mice to increase DNA synthesis. Antiepidermal growth factor reduced DNA synthesis in cultures treated with high concentrations of serum from sham-operated mice, but not in cultures treated with serum from sialoadenectomized mice. Time course studies indicated that the time of maximum DNA synthesis was similar between cultures treated with serum from sham-operated and sialoadenectomized mice. Treatment with serum from sialoadenectomized mice for 4 d resulted in lower cell number than did treatment with serum from sham-operated mice. This effect of sialoadenectomy could be overcome by epidermal growth factor. These data indicate that sialoadenectomy, which has previously been shown to depress mammary gland development, alters the endocrine status of mice, such that serum from sialoadenectomized mice is less effective in inducing DNA synthesis by mammary epithelial cells. These differences in ability of serum to induce DNA synthesis can be explained by differences in epidermal growth factor concentration or the concentration of epidermal growth factor-like constituents. PMID- 2229598 TI - Effect of acute challenge with an extreme dose of somatotropin in a prolonged release formulation on milk production and health of dairy cattle. AB - Eight pregnant Holstein cows were given weekly injections of 15 g of recombinant bST over a 2-wk period for a total dose of 30 g to determine signs of acute toxicity. Cows were monitored intensively throughout the study, and samples were taken for analyses of hormones, metabolites, chemistries, hematology, and urine analytes. Animal health throughout the study was generally excellent. Mean rectal temperatures were significantly higher in treated cows (38.7 vs. 39.2 degrees C). Least squares means for 3.5% FCM production were 15.9 and 23.0 kg/d, and net energy intakes were 29.4 and 26.9 Mcal/d for control and treated cows, respectively. Somatotropin concentrations reached more than 250 ng/ml on d 10 and remained above 200 ng/ml. Insulin and glucose concentrations were also increased but returned toward baseline values. Free fatty acid concentrations were higher in treated cows, but beta-hydroxybutyrate was not affected. Most hematological measurements were unaffected except for a reduction in erythrocyte number in treated cows and decreases in hematocrit and hemoglobin, but values were within clinically normal ranges. Although cows received in 2 wk a dose that was equivalent to the amount administered during more than 2 yr of continuous use, no signs of acute toxicity to bST were observed. PMID- 2229599 TI - Effects of preventing periparturient hypocalcemia in cows by parathyroid hormone administration on hematology, conglutinin, immunoglobulin, and shedding of Staphylococcus aureus in milk. AB - The effects of hypocalcemia at parturition on concentrations of serum immunoglobulin and conglutinin, number of bacteria shed into milk, and leukograms of dairy cows were investigated from -4 wk prepartum to 4 wk postpartum. Ten healthy multiparous Holstein cows were fed a high calcium diet to induce hypocalcemia at parturition. Five cows received intramuscular parathyroid hormone to prevent hypocalcemia at parturition. All cows experienced a leukopenia (attributable to an absolute and relative neutropenia) during the 1st wk after calving, decreased serum conglutinin activity during the first 3 wk postpartum, and decreased concentration of serum IgG1 during the 3 wk before calving. At parturition, a large increase in organisms was found in foremilk (1000 to 10,000 times more than prepartum values). Neither the hematological changes nor the decreased immunoglobulin concentration was influenced by hypocalcemia or the development of milk fever. This implies that the degree of hypocalcemia observed did not have a large or irreversible influence on bacterial infection, hematological, or humoral immunity changes in periparturient cows. PMID- 2229600 TI - Lymphocyte blastogenesis inhibition by milk whey as an indicator of mastitis. AB - Sixty milk whey samples prepared from quarters of five cows with a history of mastitis were tested for their ability to inhibit DNA synthesis in mitogen stimulated lymphocytes. The inhibitory activity was compared with milk SCC, electrical conductivity, pH, and the number of colony-forming bacteria in the milk. Milk whey contained factors that inhibited DNA synthesis in cultured lymphocytes. Inhibition of mitogen-induced DNA synthesis increased with the clinical severity of mastitis and with increased values of indirect indicators of mastitis. The increases in inhibition and electrical conductivity were delayed past the increases in SCC. Milk whey (10 microliters) from quarters with clinical mastitis and from quarters with SCC greater than 900,000 inhibited 96 to 100%, 84 to 100%, and 69 to 100% of DNA synthesis in 3-d cultures of lymphocytes stimulated with Concanavalin A, phytohemagglutinin P, and pokeweed mitogen, respectively. The numbers of colony-forming bacteria correlated least with the inhibitory activity. PMID- 2229601 TI - Evaluation of a chlorous acid-chlorine dioxide teat dip under experimental and natural exposure conditions. AB - A postmilking teat dip containing chlorous acid-chlorine dioxide was evaluated by experimental challenge and in two herds under natural exposure. The test product had an efficacy of 78.9% against Staphylococcus aureus and 52.5% against Streptococcus agalactiae in the experimental challenge trial. The product was compared with a 1% iodine product in a 15-mo natural exposure study. Post-dipping with chlorous acid-chlorine dioxide reduced incidence of udder infection by major mastitis pathogens 36.1% when data were combined from the two herds. The 1% iodine and the chlorous acid-chlorine dioxide products were not equivalent for major mastitis pathogens; the test product was more effective. Incidence of udder infection by environmental mastitis pathogens was reduced 36.8% in both herds combined. Efficacy of the two teat dips was equivalent for environmental pathogens. PMID- 2229602 TI - Videomicroscopic comparison of bull sperm and leukocyte chromosome areas as related to gender. AB - Chromosomal areas from metaphase spreads of male bovine leukocytes were digitized and sex chromosomes identified using videomicroscopy. Autosomal areas were ranked in descending order within a cell and assigned to two categories based on alternating rank. X and Y chromosome areas were assigned to respective categories. Areas were divided by 4 to make their sum equivalent to sperm DNA content. Data were analyzed before and after inclusion of sex chromosomal areas. Before X and Y inclusion, rank contributed to difference in chromosomal areas. Rank by category interaction and category effects did not contribute to area variation. After X and Y inclusion, area variation was due to rank by category interaction, rank, and category. Differences between sums of chromosomal areas across categories was 3.57%. Head areas of morphologically normal sperm with intact acrosomes were digitized using the same optics as chromosomal areas. Sum of corrected chromosomal areas per category was used in discriminant analysis to assign sperm head areas to two categories with .5 prior probabilities. Assignment resulted in 1037 sperm in one category and 1177 in the other. Difference between largest sperm head area classes across categories was 3.2%. Discrimination of sperm head areas, based on sum of chromosomal area and measured with computerized videomicroscopy, may be used to evaluate sex of bovine spermatozoa. PMID- 2229603 TI - Digesta kinetics in sheep and cattle fed diets with different forage to concentrate ratios at high and low intakes. AB - Effect of maintenance and ad libitum intakes on digesta kinetics was studied with six ruminally fistulated cows and six ruminally fistulated wethers to validate the use of sheep as a model of cattle. Complete diets were made up of ratios of alfalfa:cracked corn and soybean meal of 80:20, 55:45, and 30:70. The rate of passage of Cr-mordanted alfalfa and soybean meal in the reticulorumen was negatively related to percentage of concentrate in the diet in both species at low intakes. Passage values of particulate and liquid markers were faster at high than at low intakes in both species for all diets. Rumen liquid volume increased with intake only in the cows on the low and intermediate concentrate diets. No substantial differences were found in particulate passage values between sheep and cattle. However, liquid passage rates from the rumen and the differentials between liquid and particulate dilution rates were higher in cows than in sheep for all diets at both intakes. These results together with those for digestibility data reported in a previous communication suggest that caution should be exercised when extrapolating results from one species to the other. PMID- 2229604 TI - Overall efficacy of chronically administered recombinant bovine somatotropin to lactating dairy cows. AB - Recombinant bST at daily dosages of 0, 10.3, 20.6, and 41.2 mg/d were injected for 266 d into 8, 10, 9, and 9 Holstein cows, respectively. Treatment effects of recombinant bST were assessed for milk production traits, BW, blood components, and health and reproductive variables. Data reported compare controls to all bST treated cows. There was an average increase of 18% in 3.5% FCM for bST versus control cows. This increase resulted in enhanced feed efficiency for bST cows, as their DM intakes were not elevated above those of the control cows. Recovery of BW was similar between control and bST groups. Milk composition was unaffected except for a slight decrease in protein percentage during the first 9 wk of treatment, and an elevated SCC between wk 19 and 28. Blood parameters were not different between control and bST cows, except for hematocrit, which decreased with bST treatment. The only health and reproductive parameters affected by bST were mastitis and days open, which were increased in the highest dosage groups. PMID- 2229605 TI - Dose response of dairy cows to ammonium salts of volatile fatty acids. AB - In previous studies ammonium salts of a mixture of isobutyrate, 2-methylbutyrate, isovalerate, and valerate were fed in a corn silage, corn, corn gluten meal, and urea diet to Holstein cows throughout lactation to define the optimum level of ammonium salts of milk production. The objective of this work was to conduct another dose response study using other forage and protein sources and to determine the effects of decreasing VFA intakes as lactation advanced. The concentrate portion of the diet contained 0, .4, .8, 1.2, or 1.6% ammonium salts of VFA. The forage to concentrate ratio was 50:50, 60:40, and 70:30 for the first, middle, and last third of lactation, respectively. The study was conducted at four university locations using 191 Holstein cows. Feeds used included corn silage, alfalfa silage or hay, corn, soybean meal, minerals, and vitamins. Treatment x location interactions were significant for milk yield during early lactation. During mid- and late lactation, supplemental VFA (.8%) improved milk and protein yield. Milk composition was not greatly affected by feeding VFA. In mid-lactation, cows fed .8% ammonium salts of VFA ate more feed than did controls. Feed efficiencies were similar among groups throughout the experiment. Cows fed VFA tended to gain less BW during lactation than did controls. Health and reproduction were not different among groups. PMID- 2229606 TI - Efficacy of chlorhexidine as a postmilking teat disinfectant for the prevention of bovine mastitis during lactation. AB - A natural exposure trial was conducted for 12 mo in a herd of 150 lactating Jersey cows to determine efficacy of a .35% chlorhexidine teat dip containing a glycerine emollient for the prevention of bovine intramammary infections. Right teats of cows were dipped in the experimental teat dip after milking machine removal and left teats were not dipped. The herd was free of Streptococcus agalactiae and had a low prevalence of Staphylococcus aureus. Most new major pathogen intramammary infections resulted from Streptococcus species, primarily Streptococcus uberis and Streptococcus dysgalactiae. New infections by Streptococcus species were significantly lower in teats dipped in chlorhexidine than in undipped teats. Overall efficacy of the chlorhexidine teat dip against major mastitis pathogens was 50%. The experimental teat dip also reduced coagulase-negative Staphylococcus species infections 49.0% and Corynebacterium bovis infections 65.2%. Overall efficacy against minor mastitis pathogens was 54.0%. No irritation or chapping of teats dipped in the experimental teat dip was observed. PMID- 2229607 TI - The effect of sucrose application and implantation of mutans streptococci on the microbial composition of three-week experimental plaque--an in situ study. AB - This study describes the predominant cultivable microflora of three-week-old plaque samples obtained from human enamel sites, on the basis of microbial identification of over 9000 fresh isolates. Lower removable appliances, on which were mounted enamel sections and slabs, were worn by five young adult subjects under three experimental protocols. These were (1) 'normal' plaque conditions, (2) extra-oral sucrose applications nine times daily, and (3) inoculation of each subject's own mutans streptococci onto the enamel test sites and sucrose applications, as described above. With the exception of slightly higher proportions of Gram-negative bacilli associated with slab plaque following sucrose application, no significant differences in percentage or absolute counts of organisms were found between normal and sucrose plaques. The inoculation of mutans streptococci, combined with extra-oral sucrose applications, was associated with significantly higher percentages and absolute mean counts of both mutans streptococci and lactobacilli, and lower proportions of S. sanguis and S. oralis. Although the isolation frequency of mutans streptococci increased in all subjects and the overall mean proportion rose following inoculation, considerable inter-subject variation was seen in mean percentage counts of these organisms isolated from the three-week plaque samples. PMID- 2229608 TI - An intra-oral appliance study of the plaque microflora associated with early enamel demineralization. AB - An intra-oral appliance model was used to investigate the composition of the plaque microflora associated with early enamel demineralization. Enamel sections, with exposed windows, were mounted on lower removable appliances, and the devices were worn by volunteers for three-week periods under three experimental conditions. These were: (1) "normal" plaque conditions, (2) extra-oral sucrose applications nine times daily, and (3) inoculation of each volunteer's own mutans streptococci onto the test sites and sucrose applications as described for (2). After 21 days, the plaque overlying each window was removed, and the bacterial composition was determined. Changes in mineral content of the associated enamel were measured by microradiography and microdensitometry, and the total mineral loss (delta z) that had occurred at each site was calculated. The 144 sites studied were divided into four demineralization groups by delta z value, with an increase in mineral loss from group 1 to group 4. A progressive and significant increase in the isolation frequency of mutans streptococci occurred from delta z group 1 to group 4 sites. These organisms were isolated from the plaque of every location with enamel mineral loss of over 1000 delta z units, but were not detected in 27% of the group 3 sites. Lactobacilli comprised 2% to 3% of the total cultivable microflora in groups 1-3 sites, but were found in significantly higher proportions (18%) at those enamel sites experiencing the most extensive mineral loss (group 4). No significant relationship was found between demineralization and the levels of Actinomyces species or Veillonella.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229609 TI - Primary structure and anticandidal activity of the major histatin from parotid secretion of the subhuman primate, Macaca fascicularis. AB - A major macaque histatin (M-histatin 1) from the parotid secretion of the subhuman primate, Macaca fascicularis, was isolated by gel filtration on Bio-Gel P-2 and purified to homogeneity by reversed-phase high-performance liquid chromatography on a TSK-ODS C18 column. The complete amino acid sequence of M histatin 1, determined by automated Edman degradation, is: (formula; see text) M histatin 1 contains 38 amino acid residues, a phosphoserine at residue 2, has a molecular weight of 4881.8, a calculated pI of 8.5, and histidine forms 26.3% of the mass. The hydropathicity plot of M-histatin 1 predicts that the molecule is entirely hydrophilic, and Chou-Fasman secondary prediction indicates that the polypeptide is devoid of alpha-helix and beta-sheet conformation in aqueous solutions but contains a series of beta turns. M-histatin 1 includes a six-amino acid insert (residue 10-15) not present in human histatins and, with the introduction of gaps to maximize homology, it displays 89% and 91% sequence similarity with human histatins 1 and 3, respectively. M-histatin 1 exhibited fungicidal and fungistatic effects against the dimorphic pathogen, Candida albicans, in three separate bioassays. Its anticandidal effects were comparable with or greater than those of human histatins 1, 3, and 5. M-histatins 2, 3, and 4 were not sequenced directly because insufficient materials were available, but the amino acid composition of M-histatin 3 was nearly identical to that of the N terminal 20 amino acid residues of M-histatin 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229610 TI - mRNAs for PRPs, statherin, and histatins in von Ebner's gland tissues. AB - A search was made for expression of genes for proline-rich proteins (PRPs) and other salivary-type proteins, including statherin and histatins, in taste-bud tissues of mice and primates because of previous genetic findings in mice (Azen et al., 1986) that Prp and taste genes for certain bitter substances are either the same or closely linked. Taste-bud tissues and other tissues were tested for specific mRNAs with labeled DNA probes by Northern blotting and in situ hybridization. It was found that PRP mRNAs were present in von Ebner's glands of mice and macaques, and that there was a much greater degree of PRP mRNA induction in mouse parotid (16-fold) than in von Ebner's gland (two-fold) after in vivo isoproterenol stimulation. This difference may be due, in part, to differences in autonomic nerve innervation. Statherin and histatin mRNAs were found in macaque taste-bud tissues containing von Ebner's gland, and statherin protein was found in human von Ebner's gland by immunohistochemistry. The finding of PRP gene expression in von Ebner's gland, whose secretions have been suggested to play a role in taste stimulation, adds further support to a possible function of PRPs in bitter tasting. The possible functions of statherin and histatins in von Ebner's gland secretions may be related to statherin's regulation of salivary calcium and histatins' antibacterial and antifungal properties. PMID- 2229611 TI - Effect of solution composition on morphological and structural features of carbonated calcium apatites. AB - The composition of enamel mineral corresponds to that of a calcium carbonato apatite. For insight to be gained into the precipitation of carbonato-apatites having specific properties (crystal size, morphology, and carbonate incorporation into the crystal lattice), apatites were prepared at 80 degrees C in aqueous systems having various CO3 concentrations and pH values of around 7.5 or 10.5 (+/ 0.5). The various preparations had a wide range (0.005 to 0.19) of CO3/Ca molar ratios that bracket the ratios found in porcine enamel mineral at various developmental stages. Fourier transform infrared spectroscopy (FTIR) and x-ray diffraction analyses showed that the calcium apatites precipitating at neutral pH incorporated the carbonate into both the hydroxyl and phosphate ion sites in their lattices (A,B-types), whereas the preparations made at the alkaline pH (high OH-(-)CO3(2-)-competition) or in the presence of fluoride (F-(-)CO3(2-) competition) yielded only the B-type carbonato-apatite. It was also ascertained that the size and morphology of the carbonato-apatites, assessed by specific surface area determination and high-resolution electron microscopy, were highly dependent on the driving force for precipitation and the presence of regulators (CO3(2-) and F-) in solution. In neutral media, early precipitates were thin ribbon in appearance, but grew into crystals having flattened-hexagonal cross sections. In the presence of fluoride or in alkaline media, acicular apatite crystals, precipitated initially, grew into large rod-like carbonato-apatites having a symmetric-hexagonal cross-section. In both neutral and alkaline solutions, carbonate inhibited the growth of apatite crystals along their c axis, leading to the formation of bulkier crystals. The formation of carbonato-apatites at the neutral pH and their properties are consistent with observations made on enamel minerals formed in the early developmental stages. PMID- 2229612 TI - Polymorphism of submandibular-sublingual salivary proteins which promote adhesion of Streptococcus mutans serotype-c strains to hydroxyapatite. AB - Previously, we showed that human submandibular-sublingual (SMSL) salivas contain one or more proteins, Mr circa 300,000 daltons, which specifically promote adhesion of Streptococcus mutans serotype-c strains to hydroxyapatite. Also, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that the adhesion-promoting proteins (APPs) exhibit heterogeneity. The aims of the present study were to determine whether APPs are generally present in human SMSL salivary secretions and to characterize the noted heterogeneity. Acid-stimulated SMSL saliva samples were obtained from 54 Japanese subjects, and Mr values were obtained by SDS-PAGE. APPs were present in all saliva samples examined, though at significantly different concentrations. The APPs occurred as either single (20 subjects) or double bands (34 subjects), with a mean Mr (88 bands) of 297 kD and a range of 248-338 kD. A plot of the frequency distribution of the APPs according to Mr showed a trimodal distribution, with mean Mr values, standard deviations, and ranges for the three groups being 265 (S.D., 6.9; range, 248-278), 293 (S.D., 6.7; range, 280-305), and 320 (S.D., 7.0; range, 310-338) kD. Variations of Mr within groups may be attributed to experimental variation, although microheterogeneity cannot be excluded. Differences between groups can best be explained in terms of three polymorphic proteins, with low (L), intermediate (I), and high (H) Mr values. Six phenotypes were detected with L, I, H, LI, LH, and IH Mr bands. A Hardy-Weinberg analysis showed that the phenotype data fit a single gene, three-alleles model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229613 TI - Phenotypic changes of rabbit mandibular condylar cartilage cells in culture. AB - The present study describes the behavior of mandibular condylar cartilage (MCC) cells as a function of time in primary culture, since it is not yet clear whether these cells maintain their phenotype in culture. MCC cells from New Zealand white rabbits were seeded at high density and cultured in DMEM containing 50 micrograms/mL ascorbic acid and 10% fetal bovine serum. These cells appeared as a heterogeneous population and changed their shape, size, and refractivity as cultures aged. Cartilage-like cells, which always dominated the culture, were infiltrated with a minority of fibroblast-like cells. Cell number increased progressively, and cultures reached confluence at nine days. Antibody activity for cartilage-specific glycosaminoglycan was determined by ELISA assay. This reaction reached a maximum at six days and decreased thereafter. Cultures stained with Alcian blue (pH 1.0) supported these results. Cytoplasmic mRNA analysis indicated that the transcription of type II collagen gene was present at all time points. Type I collagen and alkaline phosphatase mRNA levels showed progressive increases from 12 h to nine days, with significantly higher values in cells cultured for six, nine, and 12 days than in cells collected from earlier time points. These results suggest that in our present culture system, MCC cells undergo phenotypic changes that resemble their maturation processes in vivo. PMID- 2229614 TI - Effect of Pd on the clinical performance of amalgam. AB - The purpose of this study was to determine the effect of a small amount of Pd on the clinical performance of a high-copper spherical-particle dental amalgam. Two identical alloys, with and without 0.5% Pd, were investigated. The marginal fracture, surface texture, and surface luster of 193 clinical restorations were evaluated at one year, those of 182 at two years, and those of 144 at three years of service. In vitro corrosion tests of anodic polarization and constant potential coulometry were also conducted. Over the three-year period, the results showed no differences in marginal fracture or surface texture between the two alloys. However, the alloy with Pd showed a significant superiority in surface luster over this time period. Both corrosion tests showed less electrochemical activity on the part of the alloy containing Pd. PMID- 2229615 TI - A new, small-color-difference equation for dental shades. AB - Traditionally, dental-shade-guide standards are designated in terms of Munsell hue (H), value (V), and chroma (C). However, delta E color differences proposed as ADA tolerances for shade guides are in the CIE L*a*b* system. The purpose of this study was to evaluate a new color-difference equation, delta EM = C delta H/5 + 7 delta V + 4 delta C for estimation of small color differences by Munsell parameters. The published values of the Bioform shade-guide tooth colors determined with a Beckman spectrophotometer were used. Color differences among 276 combinations of the 24 Bioform shade-guide colors were calculated with Eq. 1, with use of the Munsell notation, and also with the CIE L*a*b* equation for delta E. An estimate of the accuracy of Eq. 1 was 0.41 delta E units when delta E CIE was below 4.0. The Vita shade-guide colors were determined with a Beckman spectrophotometer. This data set contained 16 samples, and 120 combinations were used for calculation of color difference. An estimate of the accuracy for this set of data was 0.35 delta E units when delta E CIE was less than 4.0. The new color-difference equation provides a means for estimation of delta E CIE L*a*b* color difference between dental shades with Munsell notation. This equation will be useful for estimation of small delta E CIE L*a*b* values for shade-guide teeth that are designated in terms of Munsell notation. PMID- 2229616 TI - Development of horizontal tooth wear in maxillary anterior teeth from five to 18 years of age. AB - Sizes of horizontal wear facets of maxillary anterior teeth were studied longitudinally from the primary dentition at age five to the young adult dentition at the age of 18 years. By a planimetric method, we calculated the wear areas on dental casts taken at the ages of five, ten, 14, and 18 years from the dentition of 39 healthy, orthodontically untreated subjects with good morphological occlusion. For young adults, we also studied the association between the amount of wear and reported parafunctions, maximal bite force, salivary buffer capacity, salivary flow rate, and some cephalometric variables. Size of wear facets on all anterior teeth increased with age. Significant correlations were found between the total wear areas of the six anterior primary teeth at five years of age and those of their permanent successors at age 14 (r = 0.44) and 18 (r = 0.39). For an individual, tooth wear at five years of age was, however, of low predictive value for tooth wear in young adulthood, whereas tooth wear at 14 years of age predicted it well (r = 0.89). Highest correlations between tooth wear and background factors at 18 years of age were found for maximal anterior bite force (r = 0.44) and for the size of the gonial angle (r = 0.31). Wear of anterior teeth was not associated with reported parafunctions in young adulthood. PMID- 2229617 TI - A 24-month clinical study of the incidence and progression of dental caries in relation to consumption of chewing gum containing xylitol in school preventive programs. AB - The effect of chewing gum containing xylitol on the incidence and progression of dental caries was tested in a sample of 274 children, aged eight and nine years, of low socio-economic status and high caries rate. They were divided into two experimental groups (15% and 65% xylitol chewing gum distributed three times a day at school) and one control group (without chewing gum). The three groups were exposed to the same basic preventive program. Children who chewed gum had a significantly lower net progression of decay (progressions-reversals) over a 24 month period than did the controls. Results for the two groups chewing gum were similar. Chewing xylitol gum had a beneficial effect on the caries process for all types of tooth surfaces, and especially for bucco-lingual surfaces. The two experimental groups had a DMF(S) increment of 2.24 surfaces, compared with 6.06 surfaces for the control group. For this indicator, there was no difference between the two experimental groups. Results for the plaque index were in agreement with those of the DMF(S) increment and the net progression of decay. PMID- 2229618 TI - Variation of approximal tooth contact tightness with postural change. AB - In order to investigate the role played by posture in determining posterior dental contact tightness, we measured contact tightness of maxillary and mandibular posterior teeth in ten adult subjects, while each was initially seated upright, after each had assumed a supine posture for two h, and finally after each had returned to an upright posture for two h. The technique used for measurement of contact tightness was based on frictional force concepts and consisted of the recording of the force required to withdraw a 0.038-mm-thick stainless-steel strip that had been slipped into each contact. A decreased mean tightness of all maxillary and mandibular contacts followed the change from an upright to a supine posture. The most significant decrease (-32%) occurred at the mandibular first molar-second premolar contact, and the smallest decrease (-10%) occurred at the mandibular first premolar-canine contact. An increased mean tightness of all maxillary and mandibular contacts followed a return to an upright posture. The most significant increase (20%) occurred at the maxillary first molar-second premolar contact, and the smallest increase (8%) occurred at the maxillary first premolar-canine contact. We conclude that posterior dental contact tightness, generally regarded by dentists as a static feature of occlusion, varies significantly as a function of posture. PMID- 2229619 TI - Factors affecting dentist participation in a state Medicaid program. AB - Provider participation is one factor affecting access to care for Medicaid recipients. There is evidence that providers are increasingly limiting their acceptance of Medicaid patients. Reasons cited for physicians and dentists not participating in Medicaid include low reimbursement rates, excessive paperwork, denial of reimbursement, and bureaucratic complexities. Telephone interviews were conducted with 92 dentists in California to determine factors affecting their decisions to participate in the California Medicaid (Medi-Cal) program. Low fees, denial of payment, and broken appointments by patients were identified as the three most important problems with the program. Non-participating dentists were more concerned about broken appointments, and complicated paperwork while less likely to believe the complexity of the program had recently decreased. Participating dentists were more concerned about the lack of services covered by Medi-Cal. The fact that participating and non-participating dentist have similar concerns about most aspects of the program may indicate that dentists who currently participate in Medi-Cal may become non-participants if problems with the program are not addressed. PMID- 2229620 TI - Development and validation of a consumer quality assessment instrument for dentistry. PMID- 2229621 TI - First permanent molar restoration differences between those with or without dental sealants. PMID- 2229622 TI - Professional satisfaction among California general dentists. AB - Dentists' assessments of their jobs provide insights about issues in the dental profession needing attention. This study assessed professional satisfaction among 558 California general dentists using the 54-item, multi-faceted Dentist Satisfaction Survey (DSS). Although dentists tended to be satisfied with various facets of their jobs and careers, substantial variation in the levels of satisfaction was noted. The most satisfied dentists were older, reported higher incomes, attended more continuing education, and employed more dental auxiliaries than dentists who were the most dissatisfied. Fifty-eight percent of the variation in overall job satisfaction was explained by quality of nonwork life and satisfaction with five facets of the profession: respect received from being a dentist, the actual process of delivering care, income derived from dentistry, relationships with patients, and reduced levels of job-related stress. Dentists were most dissatisfied with the threat of malpractice, level of income, demands of managing the practice, and amount of personal time. Professional organizations should direct programs to address these issues. Dental educators should use these findings to counsel predoctoral students about the realities of dental practice and as an outcome measure of their programs. Moreover, these findings document the perceptions of the practicing profession and support several components of the SELECT recruitment strategy. PMID- 2229623 TI - Dental implant patients and their satisfaction with treatment. PMID- 2229624 TI - Development of the Geriatric Oral Health Assessment Index. AB - The development of measures for assessing oral health status is essential to the evolution and maturation of a scientific knowledge base in geriatric dentistry. The literature suggests a high prevalence of dental diseases in older adults, yet valid and reliable instruments to assess the impact of oral diseases on older individuals or populations are lacking. This paper describes the rationale for and the development of the Geriatric Oral Health Assessment Index (GOHAI), a self reported measure designed to assess the oral health problems of older adults. Following a review of the literature and consultation with health care providers and patients, a pilot instrument was developed. The GOHAI was initially tested on a convenience sample of 87 older adults. A revised instrument was then administered to a sample of 1755 Medicare recipients in Los Angeles County. The GOHAI demonstrated a high level of internal consistency and reliability as measured by a Cronbach's alpha of 0.79. Associations of the GOHAI with a single item rating of dental health and with clinical and sociodemographic supported the construct validity of the index. Having fewer teeth, wearing a removable denture and perceiving the need for dental treatment were significantly related to a worse (lower) GOHAI score. Respondents who were white, well educated, and with a higher annual household income were more likely to have a high GOHAI score, indicating fewer dental problems. Additional applications of the GOHAI are necessary to further evaluate the instrument's validity and reliability, and to establish population norms of oral health in older adult populations as measured by the GOHAI. PMID- 2229625 TI - Modeling dental health care workers' risk of occupational infection from bloodborne pathogens. PMID- 2229626 TI - But, it's not what I expected. PMID- 2229627 TI - The role of health services research in developing practice policy: development of practice guidelines. PMID- 2229628 TI - The Agency for Health Care Policy and Research: expanding the opportunities for dental health services research. PMID- 2229630 TI - Treatment of the aging face: principles and practice. PMID- 2229629 TI - Institute of Medicine activities related to the development of practical guidelines. PMID- 2229632 TI - Histologic changes in skin associated with aging. AB - This is a review of histologic changes noted in the skin of elderly individuals. Among the epidermal changes associated with skin aging are a flattened dermal epidermal junction, giving the appearance of atrophy and cellular heterogeneity. The melanocyte density declines slowly, and the Langerhans cells decrease in number with advancing age. Among the dermal changes are attenuation in the number and diameter of elastic fibers in the papillary dermis, an increase in number and thickness of the same fibers in the reticular dermis, and a coarsening of collagen fibers with an increase in density of the collagen network. A decrease in the dermal cell population as well as a functional decline in glandular activity are also noted with intrinsic aging. A decline in hair number, rate of growth, and diameter, along with a slowing of the rate of growth of nails, have been well documented with progressive aging. PMID- 2229631 TI - The aging face: a psychocutaneous perspective. AB - The cutaneous stigmata of aging may affect an individual's mental well-being, body image, and quality of life. Before proceeding with treatment, the dermatologist should take into consideration the patient's overall life situation and evaluate whether or not there is severe psychopathology and body image distortion. PMID- 2229633 TI - Cellular and molecular mechanisms of cutaneous aging. AB - There are two major theories of aging: the programmatic theory states that aging is an inherent genetic process, and the stochastic theory states that aging represents random environmental damage. Processes that are associated with cellular damage and aging are the production of free radicals (a process much enhanced after ultraviolet irradiation) and an increasing number of errors during DNA replication. Cellular manifestations of intrinsic aging include decreased life span of cells, decreased responsiveness of cells to growth signals, which may reflect loss of cellular receptors to growth factors, and increased responsiveness to growth inhibitors. All these findings are more pronounced in cells derived from photodamaged skin. Molecular manifestations of intrinsic aging, studied mainly in fibroblasts, are altered membrane composition, adhesion properties, production of extracellular matrix, and activity of the enzyme catalase. Molecular changes as a result of photoaging are less well characterized; published studies mainly target differences in composition of the extracellular dermal matrix. PMID- 2229634 TI - Clinical features of photodamage and treatment with topical tretinoin. AB - Photodamage constitutes a skin disease that merits therapy. Immediate cosmetic improvement of photodamaged skin can be achieved most dramatically by surgical means. Medical intervention has been limited until the recent advent of topical retinoic acid products for photoaging. These medications have been shown to enhance cosmesis and to produce long-lasting physiologic changes. The clinical features of photodamage and treatment with topical tretinoin are discussed. PMID- 2229635 TI - Sunscreens and the prevention of skin aging. AB - It has been well established in both human and animal skin that ultraviolet radiation from both ultraviolet B (UVB) (290 nm-320 nm) and ultraviolet A (UVA) (320 nm-420 nm) can produce profound changes in the skin that with recurrent exposure, cause it to become what we recognize as photoaged skin. Experimental studies in animals have confirmed that some sunscreen chemicals are capable of providing protection against ultraviolet-induced photoaging. It is presumed that regular use of these effective sunscreens will also reduce skin aging changes in humans. PMID- 2229636 TI - The future of topical therapy for cutaneous aging. AB - The elements of cutaneous aging have been well described and include changes of intrinsic or chronologic aging as well as changes of extrinsic or environmental aging. We also include male pattern alopecia in this category. The current dominance of tretinoin in cutaneous aging therapy is likely to be challenged by newer classes of retinoids, by topical antiandrogens, and by alternative treatments for proliferative lesions. PMID- 2229637 TI - The role of chemical peeling in the treatment of photodamaged skin. AB - Management of the aging face involves evaluation of the degree of solar elastosis, rhytidosis, and the structural changes associated with senescent skin. Chemical facial exfoliation is divided into deep, medium, and superficial based upon depth of penetration of the caustic agent used. Knowledge of the appropriate indications and technique are essential in obtaining optimal clinical results. PMID- 2229638 TI - Silicone, fibrel, and collagen implantation for facial lines and wrinkles. AB - In recent decades, cutaneous surgeons have contributed to the development of a number of implantable materials useful in the management of facial lines and wrinkles. Among these, the most effective are injectable liquid silicone, bovine collagen implant (Zyderm/Zyplast, Collagen Corporation, Palo Alto, CA) and gelatin matrix implant (Fibrel, Mentor Corporation, Goleta, CA). Each of these treatments carries its own balance of efficacy, safety, and ease of use. Clinicians are encouraged to evaluate each of these treatments in order to be able to offer a full range of injectable therapy for the aging face. PMID- 2229639 TI - Microliposuction and autologous fat transplantation for aesthetic enhancement of the aging face. AB - The accumulation of subcutaneous fat that occurs with age in certain areas of the face, ie, heavy melolabial folds, prominent jowl formation, and accumulation of fat under the chin, can make a person look older than he or she is. Removal of fat from these areas by microliposuction can enhance and rejuvenate the aging face. Similarly, fat loss in certain facial areas due to aging can result in hollow cheeks and deep grooves in the face. Its replacement through autologous fat transplantation can also rejuvenate the aging face, giving it a less angular, more rounded appearance. PMID- 2229640 TI - The face lift and ancillary procedures. AB - In this article, face lift, forehead lift, and blepharoplasty procedures are addressed. Special emphasis is made on anatomical and surgical guidelines. Some results and complications of the different procedures are presented. PMID- 2229641 TI - Distribution of glial fibrillary acidic protein (GFAP) in the intermediate filaments of the cultured cells from a patient with tuberous sclerosis. AB - We established a cell line (TS) from adenoma sebaceum of a patient with tuberous sclerosis. Through our previous studies, the abnormal cell division and dysfunction of TS cells were indicated. Glial fibrillary acidic protein (GFAP) and 55 kd protein had been to be major cytoskeletal proteins in these cells. This time we have examined the structure and distribution of cytoskeletons in TS cells with immunoelectron microscopy. TS cells were found to coexpress GFAP and vimentin-like substance; both structures seem to be closely related. The coexistence of a few kinds of proteins integrated in the cytoskeletons might lead to the abnormal behavior of the nucleus during the process of cell division. PMID- 2229642 TI - Reversible inhibition of keratinocyte thymidine incorporation by the calmodulin antagonist, W-7. AB - Although calmodulin has been suggested as an important regulator of keratinocyte proliferation, its precise role remains unknown. We employed a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), to examine the role of calmodulin on keratinocyte proliferation. N-(6 aminohexyl-1 naphthalenesulfonamide (W-5), a chlorine-deficient analogue of W-7 with little anti-calmodulin activity, was used as the control. W-7 markedly inhibited thymidine incorporation of pig epidermis at concentrations close to its anti calmodulin activity; W-5 had no effect on the thymidine incorporation. The inhibitory effect of W-7 was reversible; the removal of W-7 from the incubation medium resulted in the reinitiation of the thymidine incorporation, suggesting that W-7 is not a cytotoxic agent. These results are consistent with the view that calmodulin is an essential regulator of keratinocyte proliferation. The epidermal beta-adrenergic response, which is decreased in various hyperproliferative epidermal abnormalities, was increased in W-7-treated hypoproliferative epidermis. The epidermal SOD activity, which is also decreased in the hyperproliferative epidermis, however, was not affected by the W-7 treatment. PMID- 2229643 TI - Effects of human recombinant tumor necrosis factor-alpha (TNF-alpha) on the proliferative potential of human keratinocytes cultured in serum-free medium. AB - The effects of human recombinant tumor necrosis factor-alpha (TNF-alpha) on human keratinocytes cultured in a serum-free medium were investigated. TNF-alpha markedly suppressed cell growth. The growth-inhibitory effect was reversible and cytostatic at a concentration of 1-5 U/ml, but appeared to be irreversible and cytocidal at 10 U/ml. The growth suppressive effect was more marked when TNF alpha was added in the late growth phase or preconfluent phase than when it was added in early or mid-growth phases. No effects of TNF-alpha on cell adhesion to the substrate were observed. These results indicate that TNF-alpha is a very potent anti-proliferative agent for human keratinocytes. PMID- 2229644 TI - Kaposi's sarcoma: a light and electron microscopic study. AB - A patient with diabetes mellitus who developed the typical classic lesions of Kaposi's sarcoma is described. Our patient presented with a reddish-purple papulonodular lesion on the right foot of five months' duration. A skin biopsy specimen showed a proliferation of spindle cells forming numerous vascular slits and a diffuse extravasation of erythrocytes. The patient's sera was negative for human immunodeficiency virus (HIV) antibodies and cytomegalovirus (CMV) antibodies. Ultrastructural examination demonstrated fibroblast-like spindle cells phagocytosing and digesting red blood cells to form vascular spaces. The patient died, due to gastrointestinal hemorrhage, and the autopsy revealed an extensive visceral involvement of Kaposi's sarcoma. PMID- 2229645 TI - Malignant histiocytosis with panniculitis--a case report. AB - We report a case of malignant histiocytosis which began with the skin lesions of panniculitis. A 32-year-old woman presented with recurrent erythematous plaques, subcutaneous nodules, and ulcers on the trunk and the extremities and intermittent fever for 7 months. The cutaneous lesions consisted of erythematous and brownish irregular-shaped patches and tender cutaneous nodules 0.5-1.0 cm in diameter. Central necrosis and shallow ulcers were seen in the lesions. The patient also suffered from general fatigue, arthralgia, and weight loss. She was anemic and thrombocytopenic and had progressive impairment of liver function with coagulation defect. Histopathological study of skin lesions showed lobular panniculitis without vasculitis in the subcutaneous fat tissue. In the panniculitis lesion, moderate mixed cell infiltration consisting of lymphocytes and histiocytes was observed. Bone marrow aspiration revealed an increase in the number of histiocytes, mostly immature with active phagocytosis of erythroid cells, myeloid cells, and platelets. She was diagnosed as having malignant histiocytosis and treated with cyclophosphamide, vincristine, and prednisolone which she responded well; her fever subsided and the lesions healed with hyperpigmentation. In this patient, benign histiocytes with hemophagocytosis without immature forms were found in the skin lesions. According to our knowledge, this is the first Thai report of malignant histiocytosis with clinical features of panniculitis. PMID- 2229646 TI - Psoriasis, necrobiosis lipoidica, granuloma annulare, vitiligo and skin infections in the same diabetic patient. AB - A diabetic patient is described presenting psoriasis, necrobiosis lipoidica diabeticorum, granuloma annulare, and vitiligo and with a history of recurrent erysipelas and mycotic infections. Scrupulous physical examination excluded further systemic or cutaneous involvement. The immunological workup revealed both phenotypic and functional defects in cellular immunity. PMID- 2229647 TI - Tinea of the scrotum--report of a case presenting as lichenified plaques. AB - A 57-year-old Japanese man with tinea of the scrotum was described. His lesions on the scrotum were unusual; they appeared as lichenified plaques. PMID- 2229648 TI - Senile hypertrophy of Tyson's glands. PMID- 2229649 TI - Defective DNA repair in cultured melanocytes from xeroderma pigmentosum patients. AB - The DNA repair of ultraviolet (UV)-induced damages in primary cultured melanocytes from xeroderma pigmentosum (XP) patients and normal subjects were studied by measuring unscheduled DNA synthesis (UDS) on autoradiographs. Melanocytes were cultured in alpha-minimum essential medium (alpha-MEM) supplemented with 10% fetal calf serum (FCS), 12-O-tetradecanoyl-phorbol-13 acetate (TPA), and geneticin. The levels of UDS in XP melanocytes were compared with those in normal melanocytes. In both normal and XP melanocytes, post-UV-UDS increased dose-dependently at doses of 5-10 J/m2. XP melanocytes exhibited various levels of defect in DNA repair, depending on the type of XP. Melanocytes from XP-A patients displayed very low levels of UDS, only 6.2-8.4% that of the normal melanocytes. However, UDS values in melanocytes from intermediate groups, XP-D, XP-E, and XP-F, were relatively high, 37.2-53.5% of the control in XP-D, 50.0-66.5% in XP-E, and 38.2-46.7% in XP-F, respectively. Melanocytes from XP variant patients exhibited almost normal levels of UDS, 87.7-91.6% of those from normal subjects. The levels of UDS in XP melanocytes were very similar to those in fibroblasts isolated from the same specimens. PMID- 2229650 TI - Infiltration of melanoma cells into the type I collagen gel. AB - Melanoma cells were cultured on type I collagen gel, and the infiltration of of those cells into the gel was observed. B16 murine melanoma cells initially adopted a spherical form on the gel, but they assumed a dendritic form after infiltration into the interior. The degree of infiltration increased very rapidly and was time-dependent. No correlations between the growth rate or melanogenic activity and infiltrative potential were observed. When Syrian hamster and human melanoma cell lines were cultured, the degrees of infiltration varied. This culture system using collagen gel is considered to be a useful in vitro model of tumor cell invasion. PMID- 2229651 TI - Significance of elevated serum LDH (lactate dehydrogenase) activity in atopic dermatitis. AB - Serum lactate dehydrogenase activity (LDH) was elevated in most cases with the severe type of atopic dermatitis (AD). We examined whether LDH correlated specifically with the clinical courses and the severity of AD skin eruptions. Blood eosinophil numbers (Eo), LDH and its isoenzymes, and serum IgE (IgE) levels in eighty patients with AD were measured before and after treatment. In improved groups, Eo and LDH decreased or returned to normal values after treatment. In contrast, both levels increased in patients who worsened after treatment. Thus changes in Eo and LDH correlated well with the clinical picture. However, IgE levels did not correlate with the clinical condition. High LDH levels were detected in the severe type of AD more frequently than in the mild type. A large majority of patients with elevated LDH (higher than 300 IU/l) before treatment had more severe skin eruptions. When the LDH before treatment was within normal limits, the LDH levels in improved patients showed a further decrease. Eo, LDH and IgE were correlated closely with the clinical scores of AD, and the relationship between LDH and clinical score was the highest. Elevations of LDH5 and LDH4 among the LDH isoenzymes were more prominent in the severe type of AD than in the mild type. We concluded that LDH was useful as a marker for evaluating the disease condition and severity of skin eruption of AD. PMID- 2229652 TI - Treatment of PUVA- and retinoid-PUVA-resistant severe psoriasis with systemic cyclosporin A. AB - Twenty patients with severe psoriasis were treated with the oral administration of 5 mg/kg/day of cyclosporin A (CyA) for 12 weeks. These patients had either failed to respond to or had become unresponsive to conventional treatments including PUVA, UVB, or combinations of etretinate and PUVA or UVB. Complete clearance and marked improvement were observed in 12 (60%) and 4 patients (20%), respectively. The average score of the Psoriasis Area and Severity Index (PASI) was 26.2 before treatment, decreasing to 18.3 in 2 weeks, 8.2 in 6 weeks, and 5.1 in 12 weeks of CyA treatment. There was a tendency for patients with lower blood levels of CyA to show smaller decreases in their PASI scores. In four patients who received skin biopsies, histological improvement was noted within 10 days of treatment; epidermal thickness had decreased by 32%, intraepidermal mitoses by 66%, and parakeratosis had disappeared almost completely. No clinical side effects or alterations in laboratory values were observed that required cessation of CyA. Exacerbations of psoriasis occurred in 11 of 16 patients within 6 weeks after stopping treatment. These results suggest that CyA could be the first choice of treatment for resistant severe psoriasis. PMID- 2229653 TI - A case of Sneddon's syndrome with positive ANA and anti-cardiolipin antibodies: primary anti-phospholipid syndrome? AB - A 22-year-old woman developed ulcerative lesions on the lower extremities which usually exacerbated during the summer. Histological analysis revealed a micro thrombotic lesion in the deep dermis without inflammatory cell infiltration or fibrinoid degeneration of blood vessels. Magnetic resonance imaging revealed multiple cerebral infarctions. Abnormal laboratory findings included an elevated anti-cardiolipin antibody titer and positive speckled pattern ANA (x80), but without other manifestations or signs of SLE. FACS analysis revealed that the patient's serum reacted with ethanol fixed endothelial cells in addition to keratinocytes and peripheral blood neutrophils. This case was thought to be livedo reticularis and cerebral thrombotic lesions (Sneddon's syndrome) associated with atrophie blanche or livedo(id) vasculitis and may be one clinical subset of primary anti-phospholipid syndrome. PMID- 2229654 TI - Acquired perforating dermatosis: comparison of an acquired perforating dermatosis and perforation as an incidental histologic finding. AB - A 66-year-old Japanese woman with a rare acquired perforating disorder, usually called adult-type reactive perforating collagenosis, is reported. The patient had poorly controlled diabetes mellitus with retinopathy under oral diabetic medication. She was found to have multiple papules and umbilicated nodules on the trunk and four extremities when she was admitted and examined for the origin of jaundice and severe pruritus of sudden onset. In the biopsy specimen, collagen fibers were observed to be eliminated from the dermis through epidermal tunnel like perforations. No elastic fibers were eliminated, and serial sectioning of the specimen could not prove follicular perforation. Adenocarcinoma of the biliary duct was found to be the cause of the jaundice with pruritus. Although such cases are usually classified as acquired reactive perforating collagenosis of adult onset, proposed reclassification for acquired perforating disorders is discussed. Another case which also showed perforation and transepithelial elimination of both collagen and elastic fibers as an incidental histologic finding is described. Such elimination seems to be a not uncommon step in the formation of pruriginous eruptions. Therefore, these cases should be differentiated from acquired-type characteristic perforating disorders. PMID- 2229655 TI - Malignant eccrine tumor--a case report and a classification of tumors of eccrine sweat apparatus. AB - A case of malignant eccrine tumor and its histological findings were reported. In this case, we considered basal cell carcinoma or malignant melanoma clinically; however, the histological features matched those of malignant eccrine tumor. It has been said that it is very difficult to determine the origin of tumors of sweat apparatus; to contribute to this ongoing dialogue, the classification of tumors of eccrine sweat apparatus was also discussed. PMID- 2229656 TI - A combined case of desmoplastic trichoepithelioma and nevus cell nevus. AB - A 41-year-old woman with desmoplastic trichoepithelioma associated with pigmented nevus presented. Pigmented nevus had been present on her face at birth. She had received cryotherapy and dermabrasion at a small part of the pigmented nevus. As a result of the therapy, the discoloration disappeared. The lesion lately increased and became hard. Histologically, the lesion was composed of two distinctive but intimately mixed cellular components; nevus cells and basaloid cells. In the pigmented lesion, basaloid cells were not present. To our knowledge, this is the first reported case of desmoplastic trichoepithelioma associated with nevocellular nevus in Japan. PMID- 2229657 TI - Infundibular keratosis--report of two cases. AB - Two cases of infundibular keratosis are presented, characterized histopathologically by funnel-shaped, invaginating, epithelial lobules showing infundibular keratinization and connection with pilosebaceous structures. Lightly staining, glycogen-laden epithelial cells predominated within the two tumors. Differential diagnoses with other infundibular tumors and relationships to trichilemmoma are discussed. PMID- 2229658 TI - Phototests in Japanese patients with papulovesicular light eruption: positive provocation with UVA. AB - In six Japanese patients with papulovesicular light eruption (PVLE), photoprovocative tests were performed by irradiating UVA or UVB on the skin of the back on three consecutive days. One patient developed the typical lesion of PVLE at the test site with two consecutive daily irradiations of UVA. The remaining 5 patients had no abnormal phototest reactions. It was obvious that UVA plays an etiological role in at least some cases of PVLE. PMID- 2229659 TI - Anisotropy of the ultrasonic attenuation in soft tissues: measurements in vitro. AB - This study was designed to measure the ultrasonic attenuation within phantoms and tissue samples over a broad bandwidth and at many angles of incidence with respect to intrinsic orientations in order to elucidate both the frequency and angular dependence of the attenuation coefficient. Significant angular dependence, or anisotropy, of the attenuation was observed in canine myocardium (maximum to minimum ratio: 2.2 to 1) and a tissue mimicking phantom of oriented graphite fibers in gelatin (max to min: 2 to 1). In control studies, insignificant anisotropy was observed in the attenuation in canine liver samples and phantoms with graphite powder suspended in gelatin. Comparisons of the magnitude of variations of the oriented-fiber phantom to that predicted by a viscous relative motion model are presented. PMID- 2229660 TI - Replacing tracheoesophageal voicing sources using LPC synthesis. AB - The feasibility of using the linear predictive coding (LPC) technique to replace the voicing sources of tracheoesophageal speech was explored. Four vowels, [i], [a], [e], [u], and one diphthong [ou], produced by two male and two female tracheoesophageal speakers were analyzed by the LPC autocorrelation method. Normalized prediction error functions were used to choose the algorithm and the control parameters of the analysis. Poles of the vocal tract transfer function were selected from frames whose normalized prediction errors were close to minimum with criteria derived from transfer functions of normally produced vowels. Vowels were synthesized with the reconstructed transfer function and a synthesized excitation input. Results of an identification task indicated that the synthesized vowels were highly intelligible, and the gender of the speaker was better identified from the synthesized vowels than from the original tracheoesophageal vowels. PMID- 2229661 TI - Sound-producing sources as objects of perception: rate normalization and nonspeech perception. AB - In a variety of experiments and paradigms, researchers have attempted to determine whether or not speech perception is specialized by comparing perception of speech syllables to perception of nonspeech analogs. While nonspeech analogs appear optimal as comparisons to speech because they are acoustically similar without being recognized as speechlike, it is argued that the comparison they offer is confounded and uninterpretable. Two experiments are designed to show that, in auditory perception generally where acoustic signals are causal consequences of mechanical events, perceptual experiences are of the mechanical events themselves, not of the acoustic signal. This has two consequences. One is that there is a confounding in comparisons of speech with sine wave analogs that, whereas the one perceived as speech also has a definite causal source, the other, perceived as nonspeech, has an indeterminate or ambiguous source. A second is that response patterns in classification tasks such as those used in the literature comparing speech to nonspeech will reflect properties of the perceived sound-producing event; they will not provide a clear window on auditory system processes used to recover event properties. Experiment 3 is designed to show that perception of many acoustic-signal-producing events can appear to be special by the logic of speech-sine wave comparisons--even events that cannot plausibly be supposed to involve a specialization. PMID- 2229662 TI - Spectral and duration properties of front vowels as cues to final stop-consonant voicing. AB - The perception of voicing in final velar stop consonants was investigated by systematically varying vowel duration, change in offset frequency of the final first formant (F1) transition, and rate of frequency change in the final F1 transition for several vowel contexts. Consonant-vowel-consonant (CVC) continua were synthesized for each of three vowels, [i,I,ae], which represent a range of relatively low to relatively high-F1 steady-state values. Subjects responded to the stimuli under both an open- and closed-response condition. Results of the study show that both vowel duration and F1 offset properties influence perception of final consonant voicing, with the salience of the F1 offset property higher for vowels with high-F1 steady-state frequencies than low-F1 steady-state frequencies, and the opposite occurring for the vowel duration property. When F1 onset and offset frequencies were controlled, rate of the F1 transition change had inconsistent and minimal effects on perception of final consonant voicing. Thus the findings suggest that it is the termination value of the F1 offset transition rather than rate and/or duration of frequency change, which cues voicing in final velar stop consonants during the transition period preceding closure. PMID- 2229663 TI - The role of contrast in limiting vowel-to-vowel coarticulation in different languages. AB - Languages differ in their inventories of distinctive sounds and in their systems of contrast. Here, it is proposed that this observation may have predictive value with respect to how extensively various phones are coarticulated in particular languages. This hypothesis is based on three assumptions: (1) There are "output constraints" on just how a given phone can be articulated; (2) output constraints are, at least in part, affected by language-particular systems of phonetic contrast; and (3) coarticulation is limited in a way that respects those output constraints. Together, these assumptions lead to the expectation that, in general, languages will tend to tolerate less coarticulation just where extensive coarticulation would lead to confusion of contrastive phones. This prediction was tested by comparing acoustic measures of anticipatory vowel-to-vowel coarticulation in languages that differ in how they divide up the vowel space into contrastive units. The acoustic measures were the first and second formant frequencies, measured in the middle and at the end of the target vowels /a/ and /e/, followed by /pV/, where /V/ was /i,e,a,o,u/. Two languages (Ndebele and Shona) with the phonemic vowels /i,e,a,o,u/ were found to have greater anticipatory coarticulation for the target vowel /a/ than does a language (Sotho) that has a more crowded mid- and low-vowel space, with the phonemic vowels /i,e,e,a,c,o,u/. The data were based on recordings from three speakers of each of the languages. PMID- 2229664 TI - Phonological primitives: electromyographic speech error evidence. AB - Speech error data have been used to argue for the psychological reality of distinctive features and phonemes as well as the hierarchical ordering levels of processing for speech production. The models of production that have emerged from analysis of these data are nearly unanimous in characterizing (implicitly or explicitly) the motor output level as entirely governed by prior selection and processing of larger units, especially the phoneme. This study reports on the laboratory elicitation of sublexical speech errors by means of tongue twisters. Simultaneous audio and electromyographic recordings were analyzed. Where possible, single-motor unit discrimination was carried out to preclude the possibility of signal contamination by activation of adjacent musculature. The results indicate that traditional methods of data collection on which most speech error corpora are based are inadequate. Production models based on these corpora are not supported by the electromyographic data and must accordingly be revised. PMID- 2229665 TI - Acoustic estimations of the front cavity in apical stops. AB - Sweep-tone measurements of front-cavity resonances in apical stops are reported. Volumes inferred from resonance frequency data are presented as a function of place of articulation. The results indicate that, for post-dental points of contact, a cavity located under the tongue tip is formed. It is shown that this sublingual cavity plays a very important role in shaping the spectral structure of apical stops. PMID- 2229666 TI - Gender comparisons of children's vocal fold contact behavior. AB - Vocal fold contact behavior was examined in separate groups of boys and girls through application of an electroglottograph(EGG). In general, a contact quotient (EGG duty cycle) showed minimal differences within and between boys and girls during sustained production of the vowels /i/, /u/, and /a/. The findings are discussed with respect to the laryngeal behavior of prepubescent children as well as the clinical utility and applicability of the EGG for examining phonatory behavior among young children. PMID- 2229667 TI - Masker fringe and binaural detection. AB - Yost [J. Acoust. Soc. Am. 78,901-907 (1985)] found that the detectability of a 30 ms dichotic signal (S pi) in a 30-ms diotic noise (No) was not affected by the presence of a 500-ms dichotic forward fringe (N pi). Kollmeier and Gilkey [J. Acoust. Soc. Am. 87, 1709-1719, (1990)] performed a somewhat different experiment and varied the onset time of a 25-ms S pi signal in a 750-ms noise that switched, after 375-ms, from N pi to No. In contrast to Yost, they found that the N pi segment of the noise reduced the detectability of the signal even when the signal was temporally delayed well into the No segment of the noise and suggested that the N pi segment of noise acted as a forward masker. To resolve this apparent conflict, the present study investigated the detectability of a brief S pi signal in the presence of an No masker of the same duration as the signal. The masker was preceded by quiet or an N pi forward fringe and followed by quiet, an No, or N pi backward fringe. The present study differs from most previous studies of the effects of the masker fringe in that the onset time of the signal was systematically varied to examine how masking changes during the time course of the complex fringe-masker-fringe stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229668 TI - Detection of frequency modulation (FM) in the presence of a second FM tone. AB - A series of three experiments was undertaken to investigate detection of sinusoidal frequency modulation (FM) in the presence of FM at a separate frequency. The first experiment measured detection of modulation for an FM tone with a modulation frequency (fm) of 6 Hz as a function of carrier frequency (fc) under three conditions: (1) in quiet, (2) in the presence of a 2500-Hz pure tone, and (3) in the presence of a 2500-Hz FM tone with fm = 6 Hz, modulating in phase with the signal. Detection of FM in the presence of the second FM tone was worse than for either the signal presented in quiet or in the presence of the unmodulated tone. Threshold varied as an inverse function of frequency separation between the signal and the masker. In the second experiment, FM detection for a signal with fc = 1900 Hz and fm = 6 Hz was measured as a function of the modulation frequency (fm = 2-18 Hz) of the 2500-Hz masker tone. FM detection improved significantly with increasing difference between the modulation frequencies of the signal and the masker. The final experiment measured detection of FM for a signal (fc = 1900 Hz, fm = 6 Hz) in the presence of a second FM tone (fc = 2500 Hz, fm = 6 Hz) as a function of the relative phase of the 6-Hz modulators. Detection of FM improved monotonically as a function of increasing phase difference between the two modulators. The results are discussed in terms of modulation detection interference and perceptual grouping. PMID- 2229669 TI - Uncertainty about the correlation among temporal envelopes in two comodulation tasks. AB - The threshold of a 1250-Hz tonal signal was measured in the presence of five noise bands (each 50 Hz wide, centered at 850, 1050, 1250, 1450, and 1650 Hz) under five conditions of uncertainty about the waveform type ("correlated" or "uncorrelated"), and/or the specific waveform sample to be presented. The waveform type was correlated when the temporal envelopes of all of the noise bands were the same, and was uncorrelated when the temporal envelope of the band centered on the signal differed from the common envelope of the other bands. At the low-uncertainty end of the continuum of conditions, the same waveform type was presented throughout an entire block of trials, and, in addition, the same waveform sample was presented on the two observation intervals of a single trial (but changed across trials). At the high-uncertainty end of the continuum, both the waveform type and the waveform sample were chosen at random for every observation interval. Threshold estimates obtained from trials in which both observation intervals contained the same waveform type were not affected by uncertainty about the waveform sample within a trial, nor by uncertainty about the waveform type introduced across trials. Thus the comodulation masking release, or CMR (the difference in the thresholds obtained with the uncorrelated and correlated waveforms), calculated from these types of trials was robust across all of the uncertainty conditions. However, on those trials in which one correlated interval and one uncorrelated interval were paired, threshold estimates were influenced by a bias for listeners to choose the uncorrelated interval as the signal interval, whether or not it actually contained the signal. This bias reveals the importance of recognizing the contribution of the nonsignal interval in experiments involving masker uncertainty. Parallel results were obtained using the comodulation detection difference (CDD) task. In some conditions, marked individual differences were observed. PMID- 2229670 TI - On the dependence of (f2-f1) difference tones on subject and on additional masker. AB - For a group of eight subjects showing stronger than usual irregularities in the level dependence of the quadratic distortion product, the level and phase of the (f2-f1) difference tone were measured using the method of cancellation for three sets of primary frequencies as a function of the primary levels. An additional masker seems to "linearize" the level dependence toward regular behavior. Using data sets produced with and without the additional masker, it is possible to separate two sources of quadratic nonlinearity, one with regular behavior presumably located in the middle ear and another with irregular behavior (similar to that of cubic distortion) presumably located in the characteristics of outer hair cells. Through the "subtraction" of empirically determined patterns from idealized patterns, it is possible to approximate patterns stemming from the inner-ear source alone. PMID- 2229671 TI - Perceived sound quality of reproductions with different frequency responses and sound levels. AB - Three programs (female voice, jazz music, and pink noise) were reproduced using four different frequency responses and two different sound levels. Fourteen normal hearing subjects listened to the reproduction via earphones and judged the sound quality on seven perceptual scales (loudness, clarity, fullness, spaciousness, brightness, softness/gentleness, and nearness) and a fidelity scale. Significant differences among the reproductions appeared in all scales and could be attributed to the differences in frequency response or sound level or both. Interactions between the reproductions and the programs could be explained by the relations between the spectrum of the programs and the frequency responses used. The results for the noise program were similar to those for the jazz music program. PMID- 2229672 TI - Discrimination of modulation depth of sinusoidal amplitude modulation (SAM) noise. AB - The detection of sinusoidal amplitude modulation (SAM) provides a lower bound on the degree to which temporal information in the envelope of complex waveforms is encoded by the auditory system. The extent to which changes in the amount of modulation are discriminable provides additional information on the ability of the auditory system to utilize envelope fluctuations. Results from an experiment on the discrimination of modulation depth of broadband noise are presented. Discrimination thresholds, expressed as differences in modulation power, increase monotonically with the modulation depth of the standard, but do not obey Weber's law. The effects of carrier level and of modulation frequency are consistent with those observed in modulation detection: Changes in carrier level have little effect on modulation discrimination; changes in modulation frequency also have little effect except for standards near the modulation detection threshold. The discrimination of modulation depth is consistent with the leaky-integrator model of modulation detection for standards below--10 dB (20 log ms); for standards greater than--10 dB, the leaky integrator predicts better performance than that observed behaviorally. PMID- 2229673 TI - Electrically evoked whole-nerve action potentials: data from human cochlear implant users. AB - This study describes a method for recording the electrically evoked, whole-nerve action potential (EAP) in users of the Ineraid cochlear implant. The method is an adaptation of one originally used by Charlet de Sauvage et al. [J. Acoust. Soc. Am. 73, 615-627 (1983)] in guinea pigs. The response, recorded from 11 subjects, consists of a single negative peak that occurs with a latency of approximately 0.4 ms. EAP input/output functions are steeply sloping and monotonic. Response amplitudes ranging up to 160 micro V have been recorded. Slope of the EAP input/output function correlates modestly (approximately 0.6-0.69) with results of tests measuring word recognition skills. The refractory properties of the auditory nerve were also assessed. Differences across subjects were found in the rate of recovery from the refractory state. These findings imply that there may be difference across subjects in the accuracy with which rapid temporal cues can be coded at the level of the auditory nerve. Reasonably strong correlations (approximately 0.74-0.85) have been found between the magnitude of the slope of these recovery curves and performance on tests of word recognition. PMID- 2229675 TI - Response timing constraints on the cortical representation of sound time structure. AB - The precision of spike response timing of 94 primary auditory cortex neurons was studied using conventional extracellular recording techniques in barbiturate anesthetized cats to which tone- and/or noise-burst stimuli were presented using sealed sound delivery systems. Precision of spike timing was indexed using the standard deviation of the first-spike latent period in responses evoked by repeated presentation of tonal stimuli systematically varied in frequency, amplitude, and/or repetition rate. Within a neuron, variability of first-spike timing was usually proportional to the mean first-spike latency, in agreement with previous reports. In cases where there was a systematic relation between the precision of response timing and the mean latency, a linear correlation accounted for up to 90% of the data variance. Across the 94 neurons, standard deviations seen in responses of minimum latency were related to minimal mean latencies, and were typically in the range from 0.15-1.5 ms. The data suggest that responses to transients in the cortex show a precision of spike timing which is only slightly worse than that seen in cochlear-nerve fibers. This, however, is in dramatic contrast to previous evidence on the steady-state temporal response of cortical cells, which is at least an order of magnitude poorer than that seen in auditory nerve fibers and many cochlear nucleus cells. These observations may be directly relevant to the known consequences of auditory cortex pathology in man. PMID- 2229674 TI - Cochlear action potential tuning curves recorded with a derived response technique. AB - Previous action potential (AP) tuning curve methods have used a reduction in amplitude of the probe-elicited AP as an indication of tone-induced masking. The reduction criterion used in different studies has varied from 25% to 100%. For low level probe stimuli, which elicit a low-amplitude AP, this is a sensitive indicator. In contrast, for high-amplitude AP responses elicited by high-level stimuli, the required reduction in absolute terms is large, making it an insensitive indicator. AP tuning curves have been recorded using a sensitive method for detecting masker/probe interaction with a fixed criterion, unrelated to the unmasked AP amplitude. For each masking condition, a derived response was obtained by digitally subtracting the tone-masked AP waveform from the unmasked response. Derived responses are generated if there are ANY changes in the AP waveform induced by the masker, including amplitude changes, latency changes, or even changes in AP morphology not necessarily associated with the major peaks. A fixed criterion (10 microV) of tone-derived (TD) response was used as an indication of interaction of the responses to the masker and probe. Tuning curves generated by this method were compared with those generated by conventional amplitude reduction (AR) methods. TD tuning curves show different characteristics, especially with respect to increasing probe levels. They appear to give a good representation of the array of afferent fibers responding to a probe stimulus. In addition, frequency regions making minor contributions to the AP are better represented in TD tuning curves. PMID- 2229676 TI - The representation of the spectra and fundamental frequencies of steady-state single- and double-vowel sounds in the temporal discharge patterns of guinea pig cochlear-nerve fibers. AB - Psychophysical results using double vowels imply that subjects are able to use the temporal aspects of neural discharge patterns. To investigate the possible temporal cues available, the responses of fibers in the cochlear nerve of the anesthetized guinea pig to synthetic vowels were recorded at a range of sound levels up to 95 dB SPL. The stimuli were the single vowels /i/ [fundamental frequency (f0) 125 Hz], /a/ (f0, 100 Hz), and /c/ (f0, 100 Hz) and the double vowels were /a(100),i(125)/ and /c(100),i(125)/. Histograms synchronized to the period of the double vowels were constructed, and locking of the discharge to individual harmonics was estimated from them by Fourier transformation. One possible cue for identifying the f0's of the constituents of a double vowel is modulation of the neural discharge with a period of 1/f0. Such modulation was found at frequencies between the formant peaks of the double vowel, with modulation at the periods of 100 and 125 Hz occurring at different places in the fiber array. Generation of a population response based on synchronized responses [average localized synchronized rate (ALSR): see Young and Sachs [J. Acoust. Soc. Am. 66, 1381-1403 (1979)] allowed estimation of the f0's by a variety of methods and subsampling the population response at the harmonics of the f0 of the constituent vowel achieved a good reconstruction of its spectrum. Other analyses using interval histograms and autocorrelation, which overcome some problems associated with the ALSR approach, also allowed f0 identification and vowel segregation. The present study has demonstrated unequivocally that the timing of the impulses in auditory-nerve fibers provides copious possible cues for the identification of the fundamental frequencies and spectra associated with each of the constituents of double vowels. PMID- 2229677 TI - A model for the computation and encoding of azimuthal information by the lateral superior olive. AB - A structural model is proposed for the processing of interaural intensity differences by the lateral superior olive. One fundamental assumption is that the incoming excitatory projections from the ipsilateral anteroventral cochlear nucleus innervate columns of LSO neurons serially according to threshold. A second fundamental assumption is that the inhibitory innervation from the ipsilateral medial nucleus of the trapezoid body is also serially arranged according to threshold but in the opposite direction along the LSO column. Using neurophysiological and neuroanatomical data for neuronal response curves, connectional patterns, and cell and synapse numbers, the model was formulated quantitatively and implemented for machine computation. Azimuthal location is encoded by the position along the LSO column where LSO cell firing first goes to zero. Accuracy of coding was tested for three different connectional schemes, for variations in neuronal parameters, and for cell and synapse death. Encoding is shown to be independent of absolute sound level and to vary linearly with interaural intensity difference. PMID- 2229678 TI - Sleep disturbances caused by vibrations from heavy road traffic. AB - The influence of whole-body vibrations, noise, and a combination of the two, caused by heavy road traffic (150 events/night) on sleep, subjectively experienced sleep quality, and performance was investigated under controlled laboratory conditions for male and female subjects 20-35 years of age. A room was built above a vibrator table, with the legs of the bed mounted directly on the table through holes in the floor. Vertical vibrations were found to be attenuated by the mattress with 20-40 dB for frequencies greater than 10 Hz, whereas horizontal vibrations were slightly amplified. It could be concluded that when traffic noise [50-dB (A) peak level] is accompanied by vibrations with peak levels of 0.24 m/s2 vertically and 0.17 m/s2 horizontally as measured on the frame of the bed (stimulus duration approximately 2 s, dominant frequency approximately 12 Hz), sleep is more disturbed than is the case when noise alone occurs. The amount of REM sleep, which was significantly reduced for the vibration level mentioned above, was even more disturbed when a higher exposure level, 0.34 m/s2 vertically and 0.24 m/s2 horizontally, was applied. The subjectively rated sleep quality was lower for the higher than for the lower vibration level. Performance in the morning was only influenced for the higher vibration level. It could be concluded that vibration exposure levels near the recommendation made in ISO-standard 2631 for the awake state disturb sleep in man. PMID- 2229680 TI - On the frequency separation of simultaneously evoked otoacoustic emissions' consecutive extrema and its relation to cochlear traveling waves. PMID- 2229679 TI - Critical ratio and critical bandwidth for the Atlantic bottlenose dolphin. PMID- 2229681 TI - Thoughts on the future of nursing. PMID- 2229682 TI - A new clinical career structure for nurses: trial and evaluation. The South Australian experience. AB - A new clinical career structure for nurses was planned, introduced, implemented and evaluated in South Australia in 1986. The new structure was based on the Royal Australian Nursing Federation (South Australian Branch) Model, and its trial took place in 11 health units, involving 5000 registered nurses, or one third of the nurse workforce in South Australia. The findings of the evaluation research were utilized by Government. The sociopolitical context within which the evaluation of the new clinical career structure was implemented is re-examined in this paper. PMID- 2229683 TI - Effects of early parent touch on preterm infants' heart rates and arterial oxygen saturation levels. AB - A descriptive exploratory design was used in this study to evaluate the effects of early parent touch on the heart rates and arterial oxygen (O2) saturation levels of 36 preterm infants. The infants were between 27-33 weeks gestational age at birth, and were free of congenital defects. Infants were videotaped during parent visits on up to three separate occasions during the first month of life. Parents were encouraged to interact with their infants as they usually would, and data on the infants' heart rates and O2 saturation levels were recorded every 6 seconds on a portable computer that was interfaced with the infants' monitors. Mean O2 saturation levels were significantly lower during parent touch than during baseline periods on 45% of the visits, and significantly higher during parent touch periods on 19% of the visits. O2 saturation variability was greater during periods of parent touch, and there were more abnormal O2 saturation values during parent touch than during baseline periods. Mean heart rates during parent touch were significantly lower compared to baseline on 17% of the visits, and were higher during parent touch on 43% of the visits. There were no overall differences in mean heart rates between baseline, parent touch and post-visit classifications, although heart rate variability was greater during periods of parent touch. The results indicate that preterm infants' responses to early parent touch are variable, and suggest that blanket policies that limit parent touch during the early weeks of life may not be appropriate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229684 TI - Autonomy of primary nurses: the need to both facilitate and limit autonomy in practice. AB - This paper explores the concept and implications of autonomy in relation to primary nurses. It explores the need to limit this autonomy to ensure assigned patients receive a consistent and congruent quality of care. Methods that enable primary nurses to demonstrate their pluralistic accountability, currently being used and tested in practice, are described, methods that limit the autonomy of primary nurses without compromising it. PMID- 2229685 TI - Gay men's perceptions and responses to AIDS. AB - Gay men continue to be the largest group in Canada developing AIDS. They have responded to this threat on a personal and community level. The purpose of this study was to explore the perceptions of gay men about AIDS, and how they responded to these perceptions. Data were gathered through unstructured interviews with 34 healthy gay men, from participant observations chosen from logs that described nursing interactions with gay men who had AIDS, and fieldnotes collected during AIDS education programmes with health care workers and gay men. Using constant comparative analysis, a substantive conceptual framework was developed. Trusting was identified as the basic social psychological process that determined how gay men responded to AIDS. AIDS was perceived by all gay men in this study to threaten their own health and their acceptance by society. Variables identified behaviour, ranging from denial of personal risk to taking leadership roles in organizations to fight AIDS related to the trusting theory. This theoretical explanation of gay men's responses provides direction for programmes to educate gay men about HIV-related diseases, as well as to support those who acquire the HIV. PMID- 2229686 TI - The study of psychological factors in couples receiving artificial insemination by donor: a discussion of methodological difficulties. AB - Artificial insemination by donor (AID) may be the only means by which many infertile couples are able to have a child. However, the treatment is not invariably successful and it is postulated in the literature that psychological factors may be implicated when conception does not occur. Further investigation is required to establish the nature of any relationship between psychological stress and conception after AID but designing an adequate study is confounded by many methodological difficulties. These include issues relating to ethics, recruitment, measurement and logistics. In this paper, such aspects are examined and the importance of research in this field for nursing is highlighted. PMID- 2229687 TI - Disreputable science: definition and detection. AB - This paper describes definitions of fraud and misconduct as disreputable science. Some causes and methods of detection of scientific misconduct are identified. These hallmarks of credibility are essential for nursing to advance as a science. PMID- 2229688 TI - Nursing in transition: an analysis of the state of the art in relation to the conditions of practice and society's expectations. AB - The discipline of nursing is in a process of rapid transition. In this paper, the developments are discussed that have affected nursing in its advancement to a full-grown profession. Nursing and medicine are the products of Cartesian thinking that has fragmented our perspectives on man and his living world. The consequences of this scientific viewpoint are reflected in all aspects of life. Attention is paid to advances in nursing practice and education, the development of nursing research and the emergence of a nursing science. These aspects are discussed in the context of professionalization and the position of nursing in the health care system and in society. The study findings of the Styles Report Project on the Regulation of Nursing (1985) serve as a framework of analysis. Links are made between the recommendations given in this report and the development of primary health care, the new tomorrow of a modern discipline. PMID- 2229689 TI - Student nurse attitudes to teaching/learning methods. AB - This article outlines the findings of a study which investigated the attitudes of 203 general and psychiatric student nurses from nine schools of nursing towards a defined number of teaching/learning methodologies. All students were at the end of their first year or the beginning of their second year of a 3-year first-level training. Data were collected using an instrument based on a semantic differential scale. The findings, when compared against certain variables, for example, gender, showed that there were very few significant differences in relation to the defined and tested methodologies. Students generally showed themselves to be a homogeneous group and the findings indicate that students were more positively predisposed towards student-centred teaching/learning methodologies. PMID- 2229690 TI - Nursing Clinical Teacher Effectiveness Inventory: a replication study of the characteristics of 'best' and 'worst' clinical teachers as perceived by nursing faculty and students. AB - This study determined the characteristics of 'best' and 'worst' clinical teachers as perceived by 63 baccalaureate nursing faculty and 121 BSN students in Ohio. It is a replication of the 1987 study by Knox & Mogan. The Nursing Clinical Teacher Effectiveness Inventory (NCTEI) they developed is a 48-item Likert scale checklist which described discrete teacher characteristics clustered into five subscales or categories: teaching ability, nursing competence, personality traits, interpersonal relationship and evaluation. Respondents are asked to rate their 'best' clinical teacher using the NCTEI and then their 'worst' clinical teacher. Results show that both faculty and students agree, in both Knox & Mogan's sample and this sample, that the 'best' clinical teachers are good role models, enjoy nursing, enjoy teaching and demonstrate clinical skills and judgement. The 'worst' clinical teachers are not good role models. The most critical distinguishing characteristics between the 'best' and the 'worst' clinical teachers are being a good role model and encouraging mutual respect. PMID- 2229691 TI - Significant others benefit from preoperative information. AB - Little attention has been given to the preparation of the patient's family prior to surgery, even though nurses' clinical experience suggests that family members are often more anxious than the patient. This study explored the knowledge and anxiety of spouses and significant others of patients preparing for cardiac surgery. The subjects were selected by convenience from a preoperative class offered at the hospital where surgery was to occur. Before and after the class, the subjects completed a cardiac-surgery knowledge test and an anxiety test. The significant others were significantly more anxious than the patients prior to the class. The anxiety level of significant others was significantly reduced after the class. There were no statistically significant differences between patients and significant others on the cardiac-surgery knowledge test. These results suggest that significant others may benefit from preoperative instruction. PMID- 2229692 TI - The design of a stress-management programme for nursing personnel. AB - This study identifies the stressors and coping strategies of nursing staff (students, trained staff and those who had left the profession before qualification) in a variety of ward specialisms. The research instruments included an open-ended interview concerning pre-nursing experience, perceived stressors and satisfactions, and ways of coping, and psychometric tests of self esteem, assertion, ways of coping and personality. The five most frequently cited stressors were understaffing, conflict with nurses, dealing with death and dying, overwork and conflict with doctors. Experience of stressors was related to role and seniority of respondents, with different aspects of the same stressor differentially affecting nurses at different levels of experience. Coping strategies also depended on experience. Trained staff showed more use of problem focused ways of coping, whilst students and leavers relied more on emotion focused strategies to deal with stressful situations. These differences were related to personality characteristics of respondents and to self-esteem as well as to situational characteristics of the stressful episode. Social support was important in times of work-related stress, with students in particular making good use of peer group support. Respondents were generally lacking in assertiveness and high in anxiety. Although self-esteem was generally high, leavers scored markedly less than other subject groups in the areas of personal and social self-esteem. Leavers had little prior knowledge or experience of nursing before entering training and knew few nurses or doctors: consequently, nursing failed to meet their expectations. Stress was identified as the major cause of attrition and the sources of stress are identified. This study informed a major programme of stress-management training for student nurses which began in 1988 at the North Wales School of Nursing and which is currently under evaluation. It includes relaxation therapy, assertiveness training, and on-going group discussions which foster peer-group support and which explore the stressors and coping strategies relevant to different stages of training and ward specialisms. PMID- 2229693 TI - Quantitative measurement of anxiety in patients undergoing surgery for renal calculus disease. AB - The anxiety experienced by patients undergoing surgical procedures is well documented and may affect the outcome of any operation. This has not been considered in modern urological surgery which is moving away from highly-invasive techniques towards minimal and even non-invasive procedures. Little work has been carried out to examine the patient's reaction to this new technology. This work has two aims: to assess patient anxiety before and after different procedures for renal calculus removal and to identify, where possible, factors that contribute to pre- and post-operative anxiety. The main method of quantifying stress was the measurement of palmar sweat by means of an evaporimeter. Other measurements used were a bi-polar visual analogue scale and the Spielberger State Anxiety Questionnaire. The results of the study demonstrated a highly significant reduction in the palmar sweat production (P less than 0.0001) and score obtained for the analogue scale (P less than 0.05) following open surgery, but no changes before and after treatment in any of the variables in patients undergoing percutaneous nephrolithotomy or lithotripsy. Analysis of the data in relation to the surgery demonstrated a significantly higher preoperative analogue score in patients undergoing open surgery compared with lithotripsy (P less than 0.05). Post-operatively, patients undergoing lithotripsy had a significantly higher palmar sweat response compared with patients undergoing open surgery (P less than 0.01). Pre-operatively, fear of a general anaesthetic was identified as a factor contributing to anxiety and post-operatively, pain was the most commonly identified stressor. The implications of these results to the patient and to both nursing and medical staff in terms of practice are discussed. This must include a careful pre-operative explanation. PMID- 2229694 TI - Reluctant collaborators: do patients want to be involved in decisions concerning care? AB - Against the background of the popularity of the concept of 'patient collaboration' in care, this paper describes, from the frame of reference of the patients, how they perceive being involved in decisions concerning their own treatment and nursing care. A convenience sample of 12 patients were selected. The data collection and analysis were informed to some extent by the approach known as grounded theory. Although only 12 in-depth interviews were conducted, one major theme emerged from the data and that was named 'toeing the line'. The data suggests that some patients are more concerned about doing what is right, that is, pleasing the nurse, than participating in decisions concerning care. It is contended that if nurses adopt practices which encourage involvement they may unwittingly coerse patients to comply. It is argued that patients will accept this situation even if they do not wish a collaborative role. Despite the small sample size, interesting questions are raised concerning the underlying rationale of patient involvement. The conclusion is drawn that promoting individualized care is not necessarily synonymous with active patient involvement as advocated in much of the literature. PMID- 2229695 TI - The work style of students of mental health nursing undertaking the Project 2000 schemes of training: a logical analysis. AB - The work methods of students of mental health nursing are analysed to see which are best suited to facilitate the central educational aims of the Project 2000 schemes of training. Supervised primary nursing is found to be best because it engenders a professional cognitive style and a heightened sensitivity to the empirical, research-based culture. It is argued that team nursing causes, in its practitioners, a bureaucratic cognitive style, which acts as a structural constraint upon the learning and mastery of the process skills advocated by the Project 2000 authors. PMID- 2229696 TI - Review of experimental learning theory research in the nursing profession. AB - In this paper, Kolb's theory of experimental learning theory is briefly outlined. This overview is followed by a summary of research on the theory in nursing populations. Moderate support for various propositions of the theory suggests that further research is warranted and that Kolb's model may be useful as a basis for developing instructional activities in professional nursing education programmes. PMID- 2229697 TI - Cardiac nurses: coping with stress. AB - This paper describes issues relating to coping with stress as expressed by nurses in cardiology. The data were collected at a 1-day workshop on 'Coping with Stress', sponsored by the Israel Cardiac Nursing Association in response to repeated requests from nurses in cardiology. The programme included theoretical presentations. Group work focused on the nurses' self-evaluation of coping with stress, rather than on patients' needs. Twenty-two groups of 15 nurses each worked with pre-trained group leaders on the following issues: causes and origins of stress; coping strategies and mechanisms; feelings and emotions accompanying the different coping strategies; suggestions and alternatives for improving coping skills. The group process also included experiential exercises. Analysis of the nurses' coping strategies in relation to staff, patients and their families, and work-related issues suggests four distinct coping modes. Nurses' overall responses were positive and emphasized practical benefits for future work. PMID- 2229698 TI - Conceptual and theoretical approaches to patient care: associate versus baccalaureate degree prepared nurses. AB - The purpose of the study was to determine if there is a relationship between types of entry-level preparatory nursing programmes in which a nurse receives basic nursing education and conceptual and theoretical approaches to patient care. A secondary purpose of the study was to determine if there is a relationship between entry-level basic preparatory nursing education and nursing leadership, the ability to make nursing diagnosis, and implementation, as well as evaluation of the nursing process. Three nursing practice categories were identified and included: professional, all-nurse and technical. Useable data collected by short-essay questionnaire from 343 out of 344 sample subjects were computed to determine the relationship, if any, between basic preparatory nursing education and conceptual and theoretical approaches to patient care. Decisions about three null hypotheses were made at the 0.05 level of significance utilizing analysis of covariance and the 0.01 level of significance utilizing chi-square analysis. For Hypothesis 1, the main effect for degree work when covaried with Verbal Scholastic Aptitude Test scores, Quantitative Scholastic Aptitude Test scores, time and age indicated a significance of 0.001 for all item associations in the professional, all-nurse and technical categories utilizing analysis of covariance, and 0.001 utilizing chi-square analysis. For Hypotheses 2 and 3, the main effect for degree work when covaried with the aforementioned variables indicated a significance of 0.001 utilizing analysis of covariance, and 0.001 utilizing chi-square analysis. In conclusion, the findings from the study suggest that graduates of baccalaureate degree programmes do vary in conceptual and theoretical approach to nursing care in specific nursing care situations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229699 TI - The pill and cancer: a review of the literature. A case of swings and roundabouts? AB - The literature review has been carried out to determine the effects of the contraceptive pill in relation to the development of certain cancers. Current research findings are presented, in an attempt to evaluate the risks and benefits associated with oral contraceptive use. Particular attention is paid to the findings of a recent United Kingdom National Study, which supports the controversial link between the pill and breast cancer. The actions of the combined oral contraceptive pill and the progesterone-only pill are explored regarding their influence on the ovarian, breast, endometrial and cervical cancers. A background to the incidence and risk factors associated with these cancers is given. Included is a brief analysis of long and short-term use, dose variability and chemistry of the pill. It emerges through the literature that the pill clearly has a protective function in relation to cancers of the ovary and the endometrium. However, its influence on the development of breast cancer and cervical cancer remains irresolute pending further research. In the absence of firm guidelines for advice to clients concerning the sensible use of oral contraceptives, proposals are included for a more reasoned approach to choice. PMID- 2229700 TI - Diabetic patients facing long-term complications: coping with uncertainty. AB - A major problem of diabetes mellitus lies in its complications. Fourteen Type 1 diabetic patients with severe long-term complications were interviewed on two occasions with the aim of gaining a deeper understanding of their coping strategies. The study has a qualitative design and a grounded theory approach was used. The data-based categories 'Coming to terms', 'Keeping going' and 'Making sense' serve as a framework for the presentation of the substantive issues raised by the respondents. It was found that the problem of uncertainty featured prominently. PMID- 2229701 TI - Nursing research in geriatric mental health. AB - As the population of older people in the world increases, concerns about the health and delivery of health care to these elderly people become increasingly more important. Geriatric mental health arose as a nursing specialty in response to this concern over the health of older adults. This paper focuses on a review of nursing literature relevant to the mental and cognitive health of older adults. Implications for current practice and future research are explored. PMID- 2229702 TI - Psychiatric patients' views of their lives before and after moving to a hostel: a qualitative study. AB - This study focuses upon the experiences of a group of 10 long-stay psychiatric patients as they moved from a large institution to a staffed community hostel. The residents were interviewed 2 weeks prior to moving and again 6 weeks after the move. Areas identified in the first set of unstructured interviews were followed up in the second set. Qualitative analysis of the interviews revealed seven recurrent themes that are discussed in relation to other research studies that consider how people experience the effects of institutionalization. The study tests the feasibility of unstructured interviews as a means of collecting accounts of the perceptions and experiences of a client group from which other research methods have failed to elicit detailed information. Unstructured interviews proved successful when undertaken by a researcher who was well known and accepted by the residents. Familiarity with the residents and the context of the interview was also found to be important in analysing interviews qualitatively and the study casts doubt upon the value of primary qualitative analysis of interview transcripts by researchers who have not also participated in the interviews. The methodological implications for future deinstitutionalization studies are discussed. PMID- 2229703 TI - Patients' perceptions of music during surgery. AB - Music, as an aesthetic and symbolic medium, has the ability to dispel much of the fear and anxiety associated with facing the unknown alone. As such it is an ideal support for patients undergoing surgery where a non-general anaesthetic is administered. However, it is important to consider whether, from the patient's perspective, the inclusion of music in such a situation is considered to be helpful. A pilot study conducted at an acute hospital involved interviewing 25 patients who, through an attitudinal scale and their interview responses, revealed positive support for the music that they listened to during their operation. Their remarks focused on the ability of the music, as a familiar personal and cultural medium, to ease their anxiety, to act as a distractor and to increase their threshold of pain. From a nursing perspective, such an application of music as therapy to reduce fear and anxiety may be viewed as being highly relevant to the work of the anaesthetic nurse, with regard to a more individualized and holistic approach to patient care. PMID- 2229704 TI - Evaluation of an educational programme for patients taking warfarin. AB - The outcomes of a structured warfarin patient education programme were compared with those of an unstructured programme. For both programmes, knowledge and satisfaction levels were determined, incidence of complications of warfarin therapy were noted, and prothrombin time results were examined. The 23 patients who participated in the structured educational programme were selected from among vascular surgery patients. The comparison group was composed of 10 patients who had mechanical prosthetic valves inserted. The structured programme was designed for the study, and implemented by staff nurses. The comparison group received the usual unstructured educational programme. Post-treatment assessments were made before discharge and at 1 month and 3 months after discharge. Interview guides were developed, to determine knowledge and satisfaction. At the predischarge interview, significant differences between the treatment and comparison groups were observed related to knowledge of elements of warfarin therapy. The most important effects of the programme related to specific instructions to promote safety. The interviews 1 month and 3 months after discharge demonstrated that knowledge changed in several areas for both groups. Overall, both groups were satisfied with the information they received. The majority in both groups did not experience complications. Prothrombin times were available for some patients. Those obtained indicated that prothrombin times were not consistently within the therapeutic range for 60% of the time or more. The study supports the use of a structured educational programme as one element in achieving safe, effective warfarin therapy. Reasons for changes in knowledge over time merit further exploration, as does the relationship between optimal control of therapy and educational programmes. PMID- 2229705 TI - In-hospital counselling for first-time myocardial infarction patients and spouses: effects on satisfaction. AB - Self-ratings of satisfaction were studied over 6 months in 60 male first-time myocardial infarction patients and their wives. Couples were randomly assigned to either a treatment group, where they received a simple programme of education and psychological support in addition to routine care, or to a control group, where they received routine care only. All patients completed visual analogue scales measuring satisfaction regarding their general health, life in general, care and information received. All wives completed visual analogue scales measuring satisfaction regarding information received and care the patient received. Patients and wives in the treatment group reported statistically significantly more satisfaction than those in the control group. This effect was sustained for 6 months after counselling. PMID- 2229706 TI - The congruence of elderly client and nurse perceptions of the clients' self-care agency. AB - Congruence of client and nurse perceptions is vital to mutual goal-setting as a means of achieving self-care in the elderly. The purpose of this descriptive, correlational study was to explore the relationship between nurse and elderly client perceptions of the clients' self-care agency. A sample of 40 elderly client subjects and registered nurses' selected from two community health agencies, completed a questionnaire consisting of three instruments: (a) a demographic sheet; (b) the appraisal of Self-Care Agency Scale; and (c) the Perceived Health Status. Pearson product moment correlation coefficients were significant for the relationships between: (a) client and nurse perceptions of clients' self-care agency (r = 0.42, P less than 0.01); (b) client and nurse perceptions of clients' health status (r = 0.38, P less than 0.01; and (c) nurse perceptions of clients' self-care agency and nurse perceptions of clients' health status (r = 0.44, P less than 0.01). With increasing emphasis on health promotion of the elderly in the community, identified relationships may have potential implications for gerontological and community nursing practice. PMID- 2229707 TI - Peri-operative anxiety in patients undergoing extracorporeal piezolithotripsy. AB - Twenty-four patients undergoing extracorporeal piezolithotripsy took part in this study and underwent treatment on a Wolf Piezolith 2300 Lithotripter, which does not require any type of anaesthesia and enables the patient to be treated as an out-patient. Previous work has investigated anxiety states of patients during investigative procedures and found that information given prior to the procedure is beneficial in reducing the levels of anxiety reported. Modern urological surgery carried out to remove kidney stones has progressed to non-invasive techniques with the introduction of extracorporeal piezolithotripsy (EPL). However, little work has examined the patient's reaction to this new procedure. Since patients undergoing EPL are awake throughout the procedure, it is possible to perform continuous assessment of anxiety by measurement of palmar sweat. The results demonstrated significantly increased levels of palmar sweat throughout treatment, with a return to pre-treatment levels afterwards. This was demonstrated by just under 50% (n = 10) of patients who appeared to be agitated during treatment, and by the comments made by patients about their treatment. One third of patients (n = 8) described pain as far more severe than had been anticipated when asked if they could identify a cause for anxiety. It is recommended that adequate patient preparation and education prior to the procedure should be provided, but that such education must also include a warning that some discomfort may occur. PMID- 2229708 TI - The patient's experience of diabetes and its treatment: construction of an attitude scale by a semantic differential technique. AB - An instrument for measuring attitudes towards diabetes and self-care was constructed by a semantic differential technique. The instrument contained nine adjective pairs. Factor analysis classified these into four factors: self esteem/autonomy, object evaluation, quality of life supporting factor and self strength/vulnerability. The reliability coefficient of test-retest by 28 nurses/nurse tutors was 0.93. Fifty diabetic patients completed the attitude scale for testing the validity of the instrument. Male patients had a more positive attitude towards diabetes than females. Those who had had diabetes for less than 10 years were more positive than those with a longer duration of the disease. A higher degree of education, well-performed self-monitoring of blood glucose and achievement of good metabolic control were all associated with a more negative attitude towards diabetes. A group of nurses/nurse tutors who also completed the attitude scale had a more negative attitude towards diabetes than the investigated groups of patients. PMID- 2229709 TI - The health education needs of families caring for a schizophrenic relative and the potential role for community psychiatric nurses. AB - Community care policies for the mentally ill rely, to a large extent, on the informal contribution that often seems to be made willingly by families. In financial terms alone, it has been calculated by the British Government that families caring for a relative with schizophrenia at home save the country 25 billion pounds a year. Nearly 15 years ago, it was argued that community mental health services were failing to monitor the relationships in homes where this situation prevailed and provide the support mechanisms that were required. Further, it has been noted that when there is an over-emphasis on community care, family crises can become severe and remain undetected. This paper reviews the literature relating to the needs of families caring for a schizophrenic relative at home. It concludes that a major service that should be offered to families is education about the illness, schizophrenia, itself. Strategies for undertaking this role are examined within the overall context of 'psychosocial interventions' and the literature on 'high expressed emotion'. Finally, an experimental course, funded by the Department of Health, and located in the Department of Nursing at Manchester University, is described. Here, community psychiatric nurses are being taught to recognize the value of health education for those living with a schizophrenic relative. As a consequence, a number of valuable initiatives have been developed and these are briefly outlined. PMID- 2229710 TI - Characteristics of students entering different forms of nurse training. AB - Developments in nurse training need to be based upon an understanding of the characteristics and aspirations of students. In this study, characteristics of a sample of registered nurses (n = 27) and students (n = 41) entering an undergraduate degree programme in nursing were compared with those of student nurses (n = 46) beginning training in a college of nursing. It was found that the three groups differed in terms of their social background, their reasons for becoming a nurse, their views on nursing, their perceived social competence and their views on the role of the nurse vis-a-vis the doctor. Certain sex and social class differences were also apparent. The findings are discussed with reference to the selection of students for different forms of training and the content of current nurse training programmes. PMID- 2229711 TI - Towards defining the organization of nursing care in hospital wards: an empirical study. AB - The method of organizing nursing care known as 'primary nursing' is increasingly being introduced into hospital wards on the assumption that it will have beneficial effects for both patients and staff. Operational definitions of primary nursing, essential to provide replicable research into the organization of nursing care, are, however, lacking in available research literature. This study describes the development of a questionnaire intended to identify and discriminate between three methods of organizing nursing staff and nursing work: task allocation or functional nursing, team nursing and primary nursing. The questionnaire was distributed to 36 ward sisters on 27 acute and rehabilitation care of the elderly wards. Questionnaires were returned from 17 wards, a response rate of 63%. Findings indicate that few wards meet five or more criteria for classification as a particular method of nursing organization. The findings illustrate the difficulties in matching and discriminating between wards in order to conduct research in which organizational modality is an independent variable. PMID- 2229712 TI - The nature and prevention of suffering. PMID- 2229713 TI - Education. Developing superstars. PMID- 2229715 TI - International affairs. International consultation--a partnership in shared goals. PMID- 2229714 TI - Inquiry, insights, and history. Past dialogues. PMID- 2229716 TI - Legal and ethical issues. Ethical and legal dilemmas of battered women. PMID- 2229717 TI - The nurse executive. The impaired nurse. PMID- 2229718 TI - Professional practice. The place from which the patient comes. PMID- 2229719 TI - Public Policy. Will the nurse be where the patient is? A case for setting redistribution. PMID- 2229720 TI - Research. Self-help groups offer prime areas for nurse researchers. PMID- 2229721 TI - Aid-in-dying: issues and implications for nursing. AB - A debate format describes questions arising from the Model Aid-in-Dying Act, drafted at the University of Iowa's College of Law, and the implications for nurses. The Act allows patients or their named surrogates to demand or request active aid-in-dying. The Act requires nurses and other health care providers to comply with the qualified patient's demand unless the health care provider is a registered conscientious objector. PMID- 2229722 TI - Relationships between nursing and women's studies. AB - The purpose of this study was to examine the relationships between nursing and women's studies units in institutions of higher education that have both units. A mailed survey was completed by 173 units (97 nursing and 76 women's studies) in 38 states. Seventy-eight per cent of the nursing units and 75 per cent of the women's studies units reported some type of relationship with the counterpart. Collaborative activities included courses, guest lectures, joint sponsorship of seminars, research, and many other activities. Barriers to collaboration that were identified included different geographic locations and other structural barriers, as well as units' negative views of each other, and problems unique to nursing. Recommendations to foster communication and collaboration between nursing and women's studies units are discussed. PMID- 2229723 TI - Integration of international and transcultural content in nursing curricula: a process for change. AB - A brief review of education and nursing literature indicates that it is essential to help students develop a global perspective as they prepare to practice nursing in a world of increasingly interdependent nations and people. The process currently being implemented to integrate international and transcultural content in the undergraduate nursing curriculum at a Midwestern state university is described in this article. Assessment of the school indicated that the student population and faculty are characterized by a high degree of radical-ethnic homogeneity. Assessment also included the mapping of content in all required courses in the undergraduate curriculum in the following areas: cultural differences, health care delivery systems in other countries, nursing in other countries, and international health organizations and issues. Recommendations were then made regarding content in required courses, continuation of elective courses, and informal educational strategies. Examples of these are described, as well as the resultant changes. Some of the changes described include content added and educational strategies used to integrate transcultural and international health content in required courses. Elective courses, taught both on-campus and abroad, are briefly described. Evaluation is an ongoing part of overall program evaluation. Highest priority for future planning is currently being placed on development of a semester study-abroad program and increasing cultural diversity in all students' educational experiences. PMID- 2229724 TI - Managerial interests and personal attributes of nurses. AB - This study replicated another by Hanson and Chater (1983) that investigated the relationship between interest in management roles and personality, demographic, and career background characteristics of female nurses. For the present study, 128 sophomore, senior, and master's degree students were asked to participate and a self-selected convenience sample of 69 was obtained. Three instruments were used: The Vocational Preference Inventory (VPI), to measure personality traits; a demographic data questionnaire, to measure demographic variables; and the Strong Campbell Interest Inventory, to measure managerial interests. The total sample of nurses exhibited an artistic-social-intellectual profile. The subhypothesis that nurses of different education levels would exhibit different personality profiles was supported. Analysis of VPI scores demonstrated a statistically significant association between higher educational levels of nurses and higher acquiescence scores, (F = 5.1729 with a significance level of 0.0082). Analysis of variance of Vocational Preference Inventory scale scores showed a statistically significant association between nurses interested in management and higher scores on the enterprising attribute (F = 5.7753 with a significance level of 0.0266). No significant difference was found between management and nonmanagement interest groups in demographic and career characteristics. The findings of this study contribute more insight and knowledge about nurses who select management and administrative roles. PMID- 2229725 TI - Visual clues to emotional states: Rodin's "Burghers of Calais". AB - In the well-known, recorded Gsell-Rodin conversations of 1911, Gsell summarized Rodin's theory of the expressiveness of the human image: "Generally the face alone is considered to be the mirror of the soul: the mobility of the features of the face seems to us the unique exteriorization of the spiritual life. In reality, there is not one muscle of the body that does not express variations within. Each speaks of joy or sadness, enthusiasm or despair, calm or rage. Out stretched arms, an unrestrained torso can smile with as much sweetness as eyes or lips. But in order to be able to interpret all aspects of the flesh, one must be trained patiently in the spelling and reading of the pages of this beautiful book" (Art: Conversations With Paul Gsell. Translated by deCaso J, Sanders PB. Berkeley, CA, University of California Press, 1984, p 10). The question thus arises, how can we as students of the human condition undertake this necessary training? How might we develop the aesthetic senses to appreciate the legibility of the human face and form more fully? For assistance in this undertaking we naturally turn to the artist. For the artist "sees" the world through eyes trained to acutely appreciate color, light and shadow, surface and volume, and inner truth. In particular, the education and training of Rodin, and the development of his artistic technique and insight, offer the health care professional rich intellectual material for this study. A closer look at the conception and evolution of Rodin's masterpiece, "The Burghers of Calais," amply illustrates this vision. PMID- 2229727 TI - Elimination of after-hours care at a university health service. PMID- 2229726 TI - Ambulatory care for patients with acute leukemia: an alternative to frequent hospitalization. AB - Over the past 5 years, 23 cancer patients diagnosed with adult acute leukemia have been able to receive their required therapies primarily on an ambulatory basis. This included chemotherapy, antimicrobials, and blood product infusions. The ambulatory primary nurse has been a vital facilitator in designing and implementing a care plan that includes drug administration, symptom management, and the complex coordination of community resources. The relationship that develops between the patient, family, and primary nurse is also a key factor in the effectiveness of such an ambulatory program. PMID- 2229728 TI - Health education in higher education's future. PMID- 2229729 TI - The fear of understanding schizophrenia and the avoidance of the acutely disturbed student. AB - Although it is generally believed that a treatment that is more effective than its alternatives will be used, psychological treatments for schizophrenic and other psychotic reactions have been avoided despite the evidence of their effectiveness from the time of "moral treatment" to the present. Less effective (or even destructive) treatments have been seized upon, in part because they do not require understanding patients. Understanding them means facing facts about ourselves, our families, and our society that we do not want to know, or, in the case of repressed feelings and experiences, do not want to know again. This reluctance to understand is particularly tragic in the case of the acutely disturbed college student, whose crisis may lead either to reorganization at a higher level of functioning and growth or to a wasted life. The central role of terror in producing symptoms and the genesis and handling of symptoms, including delusions and hallucinations, are briefly discussed. PMID- 2229730 TI - The relationship between urinary tract infections and the collegiate academic calendar. AB - College students believe that they are more likely to be ill during examination periods than at other times in the academic year. We in the health service hypothesized that urinary tract infections are not affected by the demands of the academic calendar. During a 4-year study, the university health service obtained urine culture data prospectively from 456 patients who had a total of 508 episodes of urinary tract infections. Each year, the number of urinary tract infections decreased during both midterm and final examination periods, but rebounded to higher-than-average levels in the second week following the midterm examination period, as well as during the second week of the second (spring) semester, immediately after the mid-winter recess. Mean duration of symptoms was 34 hours (range, from 12 to 60). Urinary tract infections were less common during examination periods, when students were preoccupied with academic responsibilities, but such infections increased in frequency in the period immediately after examinations, when sexual intimacy was resumed or when sexual intercourse with a new partner began. Urinary tract infections in college women, the study indicated, are primarily related to sexual intercourse, and susceptibility is only indirectly affected by the demands of the academic calendar. PMID- 2229731 TI - AIDS Info On-Line: a computer-based information system for college campuses. PMID- 2229733 TI - The toothpick debate continues. PMID- 2229732 TI - Using peer educators for a classroom-based AIDS program. AB - Frustration over their inability to reach sizable numbers of students for an AIDS education and prevention program, even after employing peer educators, prompted the staff of the SHS to devise a classroom-based program. Sixty-five faculty members gave permission for the presentations, and the students represented a captive audience for the SHS-certified peer educators. Students have given very little indication of resenting this intrusion and have, in fact, been very positive in their response. Our initial evaluation of the first 2 years of the program indicates a need for greater recruitment efforts among students to serve as peer educators and among faculty to participate. It is also evident that we need to refine our evaluative tools, especially in regard to measuring behavioral changes, through use of a pretest-posttest design. PMID- 2229734 TI - The white stuff. PMID- 2229735 TI - Impressed with implants. PMID- 2229736 TI - Balancing dental service requirements and supplies: epidemiologic and demographic evidence. AB - As a counterpoint to negative interpretations of recent trends, this article presents a positive picture of dentistry in the 1990s and 21st century. Reported trends show large increases in older dentate adults who are retaining more of their natural dentition, new diagnosis and treatment technologies, increased incidence of dental caries in older adults, increased awareness of periodontal diseases, greater interest in esthetic dentistry, and generally higher expectations for health and fitness in our society. All of these factors point to a greater need for adult dental services. Therefore, in the next 30 years, the dental profession should be prepared to provide increased amounts of diagnostic, preventive, adult operative, fixed prosthodontic, and endodontic and orthodontic services. Declines in need should be expected in children's operative dentistry, extractions, and complete dentures. PMID- 2229737 TI - Porcelain and resin veneers clinically evaluated: 2-year results. AB - A clinical comparison of two different types of dental veneers--baked porcelain veneer and heat-and-pressure processed urethane resin veneer--was made after 2 years. Although the esthetic appearance and gingival response were equal for both systems, the resin veneers had a greater tendency to chip and fracture. By the end of 2 years, 20% of the resin veneers had failed, whereas all of the porcelain veneers remained. PMID- 2229738 TI - Life-threatening hemorrhage after placement of an endosseous implant: report of case. AB - This article reports an unusual but dangerous complication of implant surgery. Minimal perforations of the lingual plate and inferior border of the mandible had been considered previously to be benign occurrences. This report demonstrates the importance of managing acute airway problems resulting from perforations. PMID- 2229739 TI - Mandibular osteomyelitis in a patient with sickle cell anemia: report of case. AB - A case is presented in which mandibular osteomyelitis and mental nerve paresthesia developed in a patient with sickle cell anemia. This infection appeared to precipitate a sickle cell crisis. The mechanisms for these patients' propensity to infection and the diagnosis and management of sickle cell osteomyelitis of the jaws are discussed. PMID- 2229740 TI - Tongue ischemia from a soft-drink can: report of case. AB - A young girl was brought to the emergency department because her tongue became entrapped while she was drinking from an aluminum soft-drink can. A dental drill was used to remove the can. The tongue was observed for 48 hours, during which an ischemic area recovered spontaneously. PMID- 2229741 TI - Evaluating tooth eruption on sealant efficacy. AB - For patients aged 5 to 9 and 11 to 14, 100 occlusal surfaces on newly erupting permanent molars were treated with a self-curing pit and fissure sealant. All teeth were categorized according to stage of eruption and sealant thickness of the coating applied. After 36 months, 75 surfaces were examined for a final evaluation; 52 surfaces (70%) did not need retreatment. Of the 23 surfaces retreated as a result of sealant loss or marginal deterioration, 18 were retreated only once in the six recall evaluations. Those molars treated originally with the operculum covering the distal marginal ridge of the occlusal surface had twice the probability for retreatment as teeth not treated until the entire marginal ridge was exposed. The thickness of the sealant coating did not affect the early signs of sealant failure. PMID- 2229742 TI - The prevalence of periodontitis in a military treatment population. AB - A group of 1,984 males and females (age range 13 to 84) at a military dental clinic were given oral examinations with full-mouth circumferential periodontal probing. Diagnoses were made both for individual quadrants and for the entire mouth using clearly defined diagnostic criteria. The results showed 37% of the subjects had gingivitis only, 33% had early periodontitis, 14% had moderate periodontitis, 15% had advanced periodontitis, 0.5% had juvenile periodontitis, and 0.5% had necrotizing gingivitis. The prevalence of periodontitis increased with age to a peak in the 45- to 50-year-age group. The proportion of periodontitis-affected quadrants, although initially lagging behind the overall case diagnoses, also increased with age. PMID- 2229744 TI - Using removable partial denture framework as matrix for pin-retained restoration. AB - A quick and easy method can restore a broken-down partial denture abutment with a pin-retained amalgam restoration. It has a high degree of patient acceptance as only one appointment is required, eliminating the need for the patient to leave a partial denture for adaptation to a wax pattern. The cost can be minimal. This technique can be used for Class II restorations; however, the practitioner must ensure sufficient clearance for the condenser to pass between the tooth and the partial denture, so all areas can be properly condensed. PMID- 2229743 TI - Patient satisfaction in four types of dental practice. AB - There has been a significant growth in alternative types of dental practice. To determine satisfaction, patients were surveyed in urban private practices, a hospital dental clinic, a neighborhood health center, and a large group practice situated in a shopping center, using a 14-item survey and a 5-point rating scale. Patient satisfaction was related to the following factors in descending order: dentist, staff, efficiency, time-cost, and accessibility. Patients rated private practice most favorably for all factors with the exception of accessibility, which was rated highest for the shopping center practice. Patients rated the hospital least favorably for all factors with the exception of dentist, which was rated least favorably for the shopping center practice. Although private practices were the most favorably perceived, alternative types of practice were also highly rated and met specific patient needs. Satisfaction was greater for older patients, for patients with less education, and for white compared with black patients. PMID- 2229746 TI - Accredited dental schools. Commission on Dental Accreditation. PMID- 2229745 TI - Periodontics in general practice: professional plaque control. AB - Traditionally the primary emphasis of preventive periodontics was daily patient performed plaque control. Recent studies indicate that frequent professional subgingival toothcleaning is a mandatory treatment for prevention of recurrent periodontitis. Pathogenic subgingival bacterial complexes are disrupted by frequent cleaning and require time to reestablish. Disease progression is prevented if the recall interval does not exceed the time required for reestablishment of a pathogenic plaque. Legally, patients have acquired the duty to comply with the prescribed recall interval. Both the patient and the practitioner will benefit from a preventive program that includes frequent professional subgingival toothcleaning. PMID- 2229747 TI - Lip paresthesia associated with a jaw mass. AB - A case is reported in which mandibular swelling and lower lip numbness were the first signs of a metastatic adenocarcinoma of the lung. The development of paresthesia, with or without other oral symptoms, requires that a diagnosis of malignancy be considered until confirmed or ruled out by tissue biopsy. A thorough head and neck examination in all patients, especially in those whose history or habits may indicate increased risk of malignancy is necessary. PMID- 2229748 TI - Clinical competence in exercise testing. A statement for physicians from the ACP/ACC/AHA Task Force on Clinical Privileges in Cardiology. PMID- 2229749 TI - Progression of native coronary artery disease at 10 years: insights from a randomized study of medical versus surgical therapy for angina. AB - Repeat coronary angiography was performed in 42 patients 10 years after randomization to medical (n = 21) or surgical (n = 21) therapy for chronic angina. The native coronary arteries were classified into 15 angiographic segments and 3 arterial trunks for analysis of progression of coronary artery disease. The incidence rate of disease progression in coronary segments was 24% and 28% in medically and surgically treated patients, respectively (p = NS). Grafted segments showed a 38% rate of disease progression, which was higher than the 18% rate of for nongrafted segments (p less than 0.001) and the overall rate of 24% for medically treated patients (p less than 0.01). Similarly, 29 (94%) of 31 grafted arteries exhibited disease progression compared with 19 (59%) of 32 nongrafted arteries (p less than 0.01) and 42 (67%) of 63 arteries in medically treated patients (p less than 0.01). In grafted vessels, disease progression occurred more often in arteries proximal (84%) to the anastomosis than in arteries distal (16%) to graft insertion (p less than 0.001). Progression occurred in 46% of proximal segments compared with 23% of distal segments (p less than 0.02). Progression was seen in 23 (55%) of 43 segments with an occluded graft compared with 30 (31%) of 96 segments with a patent graft (p less than 0.02). Ten years after randomization, medically and surgically treated patients showed a comparable rate of disease progression in coronary segments. However, surgical therapy appeared to significantly accelerate atherosclerotic progression in the grafted vessels, especially in the proximal portions. Occluded grafts also correlated with an adverse effect on disease progression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229750 TI - Coronary Artery Surgery Study (CASS): comparability of 10 year survival in randomized and randomizable patients. AB - The Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction. Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison. Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70% and an ejection fraction less than 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction less than 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p less than 0.05). After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial. PMID- 2229751 TI - Coronary lesion morphology in acute myocardial infarction: demonstration of early remodeling after streptokinase treatment. AB - Coronary lesion morphology was analyzed in 72 patients 1 to 8 days after streptokinase treatment for acute myocardial infarction and compared with lesion morphology in a control group of 24 patients with stable angina. In the streptokinase group the infarct-related artery was patent in 55 patients (76%). Compared with stenoses in the stable angina group, there were no differences in the stenosis length, severity, calcification or in the proportion located at an acute bend or at a branch point. However, lesions in the streptokinase group were more often irregular (p less than 0.005) and eccentric (p less than 0.01), had a shoulder (p less than 0.0001), globular filling defects (p less than 0.01), linear filling defects (p less than 0.00005) and contrast staining (p less than 0.05). Plaque ulceration index was higher in the streptokinase than in the stable angina group (6.2 +/- 7.9 versus 3.5 +/- 3.4, p less than 0.001). Of the 72 streptokinase-treated patients, 35 were maintained on heparin infusion until angioplasty 2 to 10 days later. At repeat angiography before angioplasty, globular lesion filling defects seen in eight patients had disappeared, whereas linear filling defects persisted in 7 of 14 cases. Fewer lesions were irregular (p less than 0.0001) and the ulceration index decreased from 7.4 +/- 10.4 to 3.0 +/- 1.6 (p less than 0.001). These data show that the lesion in the infarct related artery after streptokinase treatment is irregular and often associated with filling defects, perhaps corresponding to plaque fissuring and intraluminal thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229752 TI - Coronary plaque morphology in postinfarction patients: implications for early versus deferred coronary angioplasty. PMID- 2229753 TI - Results of primary angioplasty for acute myocardial infarction in patients with multivessel coronary artery disease. AB - The influence of multivessel coronary artery disease on the outcome of reperfusion therapy for myocardial infarction has not been fully characterized. Direct coronary angioplasty without antecedent thrombolytic therapy was performed during evolving myocardial infarction in 285 patients with multivessel coronary artery disease at 5.2 +/- 4.2 h after the onset of chest pain. Two vessel disease was present in 163 patients (57%) and three vessel disease in 122 (43%). An anterior infarct was present in 123 patients (43%), cardiogenic shock in 33 (12%) and age greater than or equal to 70 years in 59 (21%). Angioplasty of the infarct related vessel was successful in 256 patients (90%), including 92% with two vessel and 88% with three vessel disease (p = NS). Emergency bypass surgery was needed in six patients (2%). In-hospital death occurred in 33 patients (12%), including 13 with two vessel and 20 with three vessel disease (p less than 0.05). The mortality rate was only 4% in the subgroup of 101 patients who met entry criteria for thrombolytic trials. The in-hospital mortality rate was 45% in patients in shock and 7% in patients not in shock (p less than 0.01). Logistic regression analysis identified shock and age greater than or equal to 70 years as independently associated with in-hospital death. In 135 patients who underwent predischarge left ventriculography, global ejection fraction increased from 50% to 57% (p less than 0.001) and regional wall motion in the infarct zone improved in 59% of patients. Follow-up data were available in 251 patients (99%) at a mean of 35 +/- 19 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229754 TI - Multivessel coronary angioplasty from 1980 to 1989: procedural results and long term outcome. AB - From June 1980 to January 1989, 3,186 patients had coronary angioplasty of two (2,399 patients) or three (787 patients) of the three major epicardial coronary systems. A mean of 3.6 lesions (range 2 to 14) were dilated per patient, with a 96% success rate. Acute complications were seen in 94 patients (2.9%) and included Q wave infarction in 47 (1.4%), urgent coronary artery bypass surgery in 33 (1%) and death in 31 (1%). Multivariate correlates of in-hospital death included impaired left ventricular function, age greater than or equal to 70 years and female gender. Complete long-term follow-up data were available for the first 700 patients and the follow-up period averaged 54 +/- 15 months in duration. Actuarial 1 and 5 year survival rates were 97% and 88%, respectively, and were not different in patients with two or three vessel disease. By Cox regression analysis, age greater than or equal to 70 years, left ventricular ejection fraction less than or equal to 40% and prior coronary artery bypass surgery were associated with an increased mortality rate during the follow-up period. Repeat revascularization procedures were required in 322 patients (46%). Restenosis resulted in either repeat angioplasty or bypass surgery in 227 patients (32%). Repeat coronary angioplasty was performed for isolated restenosis in 126 patients (18%), for restenosis and disease progression at new sites in 85 patients (12%) and for new disease progression alone in 54 patients (8%). Coronary bypass surgery was required in 110 patients (16%) during the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229755 TI - Multivessel coronary angioplasty. PMID- 2229756 TI - Coronary angioplasty as the preferred approach to treatment of multivessel disease: promising, appealing but unproved. PMID- 2229757 TI - Plasma homocyst(e)ine levels in men with premature coronary artery disease. AB - Plasma homocyst(e)ine (that is, the sum of free and bound homocysteine and its oxidized forms, homocystine and homocysteine-cysteine mixed disulfide) levels were determined in 170 men (mean age +/- SD 50 +/- 7 years) with premature coronary artery disease diagnosed at coronary angiography and in 255 control subjects clinically free of coronary artery disease (mean age 49 +/- 6 years). Patients with coronary artery disease had a higher homocyst(e)ine level than control subjects (13.66 +/- 6.44 versus 10.93 +/- 4.92 nmol/ml, p less than 0.001). High density lipoprotein (HDL) cholesterol levels were lower (32 +/- 10 versus 46 +/- 13 mg/dl, p less than 0.001) and triglycerides levels were higher (193 +/- 103 versus 136 +/- 106 mg/dl, p less than 0.001) in the coronary disease group. Plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels were not significantly different between patients with coronary disease and control subjects. The presence of hypertension, smoking or diabetes mellitus did not significantly alter homocyst(e)ine levels in the patient or the control group. Patients who were not taking a beta-adrenergic blocking drug (n = 70) had a nonsignificantly higher homocyst(e)ine level than did patients taking this class of drugs (n = 100) (14.67 +/- 8.92 versus 12.95 +/- 3.77 nmol/ml, p = 0.087). By design, none of the control subjects were taking a beta-blocker. No significant correlations were observed between homocyst(e)ine and age, serum cholesterol, LDL cholesterol, HDL cholesterol or triglyceride levels. It is concluded that an elevated plasma homocyst(e)ine level is an independent risk factor for the development of premature coronary atherosclerosis in men. PMID- 2229758 TI - Prolonged anginal perceptual threshold in diabetes: effects on exercise capacity and myocardial ischemia. AB - Anginal perceptual threshold (the time from onset of 0.1 mV of ST segment depression to onset of angina during treadmill exercise) is prolonged in diabetic patients with coronary artery disease. In the present study, the functional significance of this perceptual abnormality was evaluated by analysis of its effect on exercise capacity and the severity of myocardial ischemia. Treadmill exercise in 32 diabetic patients and 36 nondiabetic control patients showed a close linear correlation between the time to onset of electrical ischemia (ST segment depression) and exercise capacity in both groups (r = 0.8 and 0.9, respectively; p less than 0.001). However, the slope of the relation was flatter in the diabetic group because prolongation of the anginal perceptual threshold permitted continued exercise as ischemia intensified. The anginal perceptual threshold itself showed a close linear correlation with exercise capacity in the diabetic group (r = 0.8, p less than 0.001), although in the nondiabetic group these variables were unrelated. The permissive effect of a prolonged anginal perceptual threshold on exercise capacity is undesirable as reflected by its correlation with ischemia at peak exercise (r = 0.6, p less than 0.001): the longer the threshold, the greater the exercise capacity and the more severe the ischemia. Indeed, the inverse relation between the severity of ischemia at peak exercise and exercise capacity in the nondiabetic group (r = 0.4, p less than 0.02) was completely lost in the diabetic group. Thus, in diabetic patients with coronary artery disease, anginal perceptual threshold is a major determinant of exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229759 TI - Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings. AB - To characterize the neural excitatory state of heart failure, simultaneous measurements of efferent sympathetic nerve activity to muscle (by microneurography) and rest hemodynamics were obtained in 10 normal subjects (age 25 +/- 2 years, mean +/- SEM) and 29 patients with heart failure (age 49 +/- 2 years; New York Heart Association functional class II to IV; left ventricular ejection fraction 21 +/- 1%; cardiac index = 2.16 +/- 0.13 liters/min per m2; pulmonary capillary wedge pressure 23 +/- 2 mm Hg). Sympathetic nerve activity was significantly higher in the patients with heart failure (54.7 +/- 4.5 bursts/min) than in normal subjects (16.7 +/- 2.2 bursts/min, p less than 0.001). Multiple linear regression analyses indicated that sympathetic activity in these human subjects was most strongly and inversely correlated with left ventricular stroke work index (r = -0.86, p less than 0.0001) and stroke volume index (r = 0.85, p less than 0.0001). There was a strong positive correlation between sympathetic nerve activity and pulmonary artery diastolic (r = 0.82, p less than 0.0001) and mean (r = 0.81, p less than 0.0001) pressures. Similar correlations were seen when patients with heart failure were analyzed separately. There was no significant correlation between sympathetic nerve activity and mean arterial pressure, left ventricular ejection fraction (by radionuclide ventriculography), cardiac chamber size (by echocardiography) or arterial oxygen tension in the patients with heart failure. Direct measurements of sympathetic nerve activity correlated closely with plasma norepinephrine (r = 0.72, p less than 0.0001) in patients with heart failure. Thus, sympathetic nerve activity at rest parallels impairment of cardiac performance in patients with heart failure. PMID- 2229760 TI - Serial Doppler echocardiographic follow-up of left ventricular diastolic function in cardiac amyloidosis. AB - A spectrum of left ventricular diastolic filling abnormalities noted on Doppler echocardiography has been demonstrated in patients with cardiac amyloidosis. To determine how these filling abnormalities evolve over time and the significance of any change, serial pulsed wave Doppler studies of left ventricular inflow were performed over 12.6 +/- 4.9 months in 41 consecutive patients (36 men and 15 women, mean age 59 +/- 11 years) with typical two-dimensional echocardiographic features of cardiac involvement. The measurements were peak left ventricular inflow in early diastole (E) and atrial contraction (A) velocities, E/A ratio, deceleration time and isovolumetric relaxation time. Patients were classified by mean left ventricular wall thickness into an early group (less than 15 mm) of 24 patients and an advanced group (greater than or equal to 15 mm) of 17 patients. The total group showed an increased E/A ratio (1.7 +/- 0.9 versus 1.4 +/- 0.9, p = 0.009) and decreased deceleration time (164 +/- 57 versus 174 +/- 51 ms, p = 0.11) at follow-up compared with baseline study. The early group showed significant changes in the E/A ratio (1.6 +/- 1.0 versus 1.2 +/- 0.7, p = 0.001) between the two studies. Seven patients (29%) in the early group showed a change from an abnormal relaxation or "normal" pattern to one of restriction, coincident with increased symptoms in six of these patients. Fifteen (88%) of the 17 patients in the advanced group did not show significant changes in the measures during the follow-up study, but these patients already showed a restrictive pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229761 TI - Simultaneous transesophageal atrial pacing and transesophageal two-dimensional echocardiography: a new method of stress echocardiography. AB - The diagnostic use of exercise echocardiography has been widely reported. However, transthoracic exercise echocardiography is inadequate in up to 20% of patients because of poor image quality related to exercise. In an attempt to overcome these limitations, a system was developed in which transesophageal echocardiography is combined with simultaneous transesophageal atrial pacing by means of the same probe. In a prospective study, transesophageal echocardiography was performed before, during and immediately after maximal atrial pacing in 50 patients with suspected coronary artery disease. Results of transesophageal stress echocardiography were considered abnormal when new pacing-induced regional wall motion abnormalities were observed. Correlative routine bicycle exercise testing was carried out in 44 patients. Cardiac catheterization was performed in all patients. The success rate in obtaining high quality diagnostic images was 100% by transesophageal echocardiography. All nine patients without angiographic evidence of coronary artery disease had a normal result on the transesophageal stress echocardiogram (100% specificity). Thirty-eight of 41 patients with coronary artery disease (defined as greater than or equal to 50% luminal diameter narrowing of at least one major vessel) had an abnormal result on the transesophageal stress echocardiogram (93% sensitivity). The sensitivity of the technique for one, two or three vessel disease was 85%, 100% and 100%, respectively, compared with 44%, 50% and 83%, respectively, for bicycle exercise testing; the 12 lead electrocardiogram (ECG) during rapid atrial pacing showed a sensitivity of 25%, 64% and 86%, respectively. Thus, rapid atrial pacing combined with simultaneous transesophageal echocardiography is a highly specific and sensitive technique for the detection of coronary artery disease. Ischemia induced wall motion abnormalities were detected earlier than observed ECG changes. The technique appears to be particularly suited to patients who are unable to perform an active stress test or those with poor quality transthoracic echocardiograms. PMID- 2229762 TI - Transesophageal atrial pacing or pharmacologic stress testing in detection of coronary artery disease in patients who are unable to undergo exercise stress testing. PMID- 2229763 TI - Left atrial dimensions in growth and development: normal limits for two dimensional echocardiography. AB - Reference values for normal left atrial dimensions have been based primarily on blind M-mode measurements, with no reports based on two-dimensional echocardiography to provide a comprehensive analysis of the two-dimensional measurements from infancy to old age. This report analyzes the left atrial dimensions from two-dimensional echocardiographic studies in 268 normal healthy subjects to determine normal limits and relations among linear, area and volume measurements of the left atrium. The group mean values change with body size, fitting well to the exponential growth model (r = 0.78 to 0.92). The variance about the mean (which determines normal limits) is represented effectively by a quadratic function of body surface area (r = 0.84 to 0.99). The variables determined by this modeling simplify evaluation of normal limits for any body size at any desired level of confidence, and the data are useful reference standards for interpretation of two-dimensional echocardiograms. PMID- 2229764 TI - Effects of nitroprusside on transmitral flow velocity patterns in extreme heart failure: a combined hemodynamic and Doppler echocardiographic study of varying loading conditions. AB - To explore the mechanisms of change of left ventricular diastolic filling associated with preload and afterload reduction, the influence of nitroprusside on the transmitral flow velocity pattern, pulmonary capillary wedge pressure and left ventricular pressure interaction was studied in 11 patients with end-stage heart failure. Pulsed Doppler echocardiographic recordings of mitral inflow were obtained with simultaneous high fidelity left ventricular and phase-corrected pulmonary capillary wedge pressure recordings before and during levels of nitroprusside infusion. With nitroprusside, left ventricular systolic and end diastolic pressures decreased by 14% and 41% (p less than 0.05, p less than 0.05), respectively, and cardiac output increased by 67% (p less than 0.05). The pulmonary capillary wedge-left ventricular crossover pressure decreased by 41% (p less than 0.05), but the time constant of isovolumetric left ventricular pressure decrease T was insignificantly changed. Isovolumetric relaxation time and acceleration and deceleration times of the early diastolic filling wave were significantly prolonged with nitroprusside infusion (p less than 0.05, p less than 0.05 and p less than 0.05, respectively). Peak early diastolic filling velocity was maintained (65 +/- 11 to 62 +/- 13 cm/s, p = NS) in spite of the decreased absolute crossover pressure. Changes in peak early diastolic filling velocity correlated weakly with changes in the crossover pressure (r = 0.48, p less than 0.05) and correlated better with the crossover to left ventricular minimal pressure difference (r = 0.78, p less than 0.05). Peak early diastolic filling velocity appears to be most affected by the early diastolic pulmonary capillary wedge to left ventricular pressure difference rather than the absolute pulmonary capillary wedge pressure. The lack of peak flow velocity change during nitroprusside infusion could be explained by either the associated decrease in left ventricular minimal pressure or downward shift of left ventricular diastolic pressure by the same amount as the decrease in pulmonary capillary wedge pressure. This may reflect a reduction of external constraint to ventricular distensibility produced by a reduction in filling volume in patients with a markedly dilated ventricle. Thus, a prolonged early diastolic filling period and preserved peak early diastolic filling velocity in spite of decreased left ventricular filling pressure and constant relaxation rate are associated with the beneficial effects of nitroprusside on left ventricular function in patients with severe congestive heart failure. PMID- 2229765 TI - Comparison of ventricular arrhythmia induction with use of an indwelling electrode catheter and a newly inserted catheter. AB - Two methods of serial electrophysiologic testing are in widespread use. Most commonly, the electrode catheter is removed after each study and a new catheter reinserted through the femoral vein for every subsequent test. An alternative method employs an electrode catheter that remains in place during several days of serial testing. Little is known about differences between these two methods with respect to the likelihood of induction of arrhythmia or the frequency of complications. To determine whether inducibility of sustained arrhythmia is altered or if the frequency of complications is unacceptably high with use of an indwelling catheter, a prospective randomized study was conducted in 78 patients. Each patient underwent baseline testing, several days of electropharmacologic testing with an indwelling catheter, a 24 h drug elimination period and placement of a new electrode catheter. Ventricular stimulation studies were then performed in each patient with both the indwelling and new electrode catheters. No differences were found between the indwelling and new catheter tests with respect to induction of arrhythmia, number of extrastimuli required to induce arrhythmia, rate of arrhythmia or requirement for cardioversion. Ventricular pacing thresholds were higher and effective refractory periods were slightly longer when measured with the indwelling catheter. Complications related to the 156 catheter insertions included two that may have been related to the indwelling catheter (one episode of staphylococcal sepsis and one presumed pulmonary embolism) and four that were related to invasive procedures (pneumothorax in all). There were no long-term adverse sequelae of these complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229766 TI - Determinants of the ventricular rate during atrial fibrillation. AB - Determinants of the ventricular cycle length during atrial fibrillation were examined in 52 patients. Thirty-three patients had structural heart disease and none had an accessory atrioventricular (AV) connection. The AV node effective and functional refractory periods, the shortest atrial pacing cycle length associated with 1:1 conduction, the AV node conduction time and indexes of concealed conduction in the AV node were measured in the baseline state (36 patients) and after modification of sympathetic tone by infusion of isoproterenol or propranolol (8 patients each). Atrial fibrillation was then induced with rapid atrial pacing, and the mean, shortest and longest ventricular cycle lengths were measured. Variables that correlated most strongly with the mean RR interval during atrial fibrillation were the AV node effective refractory period (r = 0.93; p less than 0.001), AV node functional refractory period (r = 0.87; p less than 0.001) and shortest atrial pacing cycle length associated with 1:1 conduction (r = 0.91; p less than 0.001). The AH interval during sinus rhythm (r = 0.74; p less than 0.001) and during atrial pacing at the shortest cycle length with 1:1 conduction (r = 0.52; p less than 0.001) had weaker correlations. Measures of concealed conduction did not improve the prediction of the mean or longest ventricular cycle length during atrial fibrillation. In conclusion, the refractory periods and conductivity of the AV node are the best indicators of the potential of the node to transmit atrial impulses to the ventricles during atrial fibrillation. The degree of concealed conduction in the AV node is a less important determinant of the mean ventricular rate during atrial fibrillation. PMID- 2229767 TI - Is atrial activation beneficial in heart transplant recipients? AB - Because of the distortion of atrial morphology that occurs during cardiac allograft transplantation in humans, the beneficial effects of properly sequenced atrial and ventricular activation are unclear in these patients. To evaluate the atrial contribution to ventricular pump performance in heart transplant recipients, arterial pressure and cardiac output during pacing from either chamber were measured in nine patients 10 +/- 1 days after transplantation. Systolic, diastolic and mean systemic arterial pressures were significantly higher during atrial pacing compared with ventricular pacing: 143 +/- 23 versus 125 +/- 20 mm Hg, 73 +/- 15 versus 66 +/- 14 mm Hg and 94 +/- 17 versus 84 +/- 16 mm Hg, respectively (p less than 0.05 for all). In addition, cardiac output decreased from 5.5 +/- 1.4 to 4.6 +/- 1.5 liters/min (p less than 0.005) for atrial versus ventricular pacing. Thus, there is a significant atrial contribution to cardiac performance in patients after heart transplantation. This may have clinical implications in those patients who later require a permanent pacemaker. PMID- 2229768 TI - Comparative value of transthoracic and transesophageal echocardiography in the assessment of congenital abnormalities of the atrioventricular junction. AB - Information obtained from transthoracic and transesophageal echocardiography (two dimensional echocardiography with spectral Doppler and color flow imaging) was compared in 17 patients with major congenital abnormalities of the atrioventricular (AV) junction (10 discordant AV connections, 1 criss-cross connection, 5 absent right connections and 1 absent left connection). The findings by either technique were correlated with findings at cardiac catheterization (12 patients) and at surgery (5 patients). In two of six patients with an absent AV connection as defined by transthoracic echocardiography, transesophageal imaging demonstrated an imperforate AV valve. In 11 of 11 patients with a discordant or criss-cross connection, assessment of AV valve and ventricular morphology (by defining the chordal attachments of both AV valves) was possible with transesophageal echocardiography (3 of 11 patients by transthoracic echocardiography); chordal straddling was detected in 1 patient and excluded in 3 others with an associated inlet ventricular septal defect. Anomalous pulmonary venous connection (one patient), atrial septal defect (three patients) and subpulmonary stenosis (five patients) were better assessed by transesophageal imaging, and atrial appendage morphology could be demonstrated in all. The transesophageal technique was less useful in demonstrating the anterior subaortic infundibulum or aortopulmonary shunt (two patients). Although systemic ventricular function could be assessed by either method with use of short-axis M mode scans, transesophageal pulsed Doppler interrogation of AV valve and pulmonary venous flow patterns provided clues to diastolic dysfunction of the systemic ventricle. PMID- 2229769 TI - Supraventricular tachycardia due to Wolff-Parkinson-White syndrome in children: early disappearance and late recurrence. AB - The clinical course of 140 patients with Wolff-Parkinson-White syndrome who had their initial episode of supraventricular tachycardia before 18 years of age was reviewed. Among those whose tachycardia began at age 0 to 2 months, it disappeared in 93% and persisted in 7%. In 31%, it disappeared and reappeared at an average age of 8 years. Among patients whose tachycardia was present after age 5 years, it was persistent in 78% at a mean follow-up period of 7 years. Accessory connection location was mapped by electrophysiologic study in 87 patients and estimated by electrocardiography in 53 patients. There were no differences in tachycardia onset or recurrence based on accessory connection location. Congenital heart defects were present in 37% of all patients, 23% of whom had Ebstein's anomaly. Among all patients who underwent cardiac catheterization, 63% of those with a congenital heart defect had a rightsided accessory connection, whereas 61% of patients with a normal heart had a left sided connection (p less than 0.01). Multiple accessory connections were found in 12% of patients with a congenital heart defect compared with 6% of those without such a defect. IN CONCLUSION: 1) supraventricular tachycardia due to Wolff Parkinson-White syndrome that begins in infancy may disappear, but it frequently recurs in later childhood; 2) if tachycardia is present after age 5 years, it persists in greater than 75% of patients; and 3) the location of the accessory connection does not affect the clinical course of tachycardia in children with Wolff-Parkinson-White syndrome. PMID- 2229770 TI - Pediatric pre-excitation: say "no" to drugs? PMID- 2229771 TI - Ventricular arrhythmias after correction of ventricular septal defects: importance of surgical approach. AB - To compare the prevalence of conduction disturbances and ventricular arrhythmias in cases of postoperative ventricular septal defect, 100 patients (50 with repair by right atriotomy, group 1; and 50 with repair by right ventriculotomy, group 2) underwent complete evaluation including an electrocardiogram (ECG) and 24 h ambulatory ECG monitoring. The two groups were comparable except for a shorter follow-up duration (7 +/- 3 versus 12.4 +/- 7 years) and a younger age at evaluation (12.4 +/- 5 versus 16.9 +/- 7 years) in group 1. Complete right bundle branch block was less frequent in group 1 than in group 2 (20% versus 50%, p less than 0.05) but three of the four patients with complete atrioventricular (AV) block detected on ambulatory monitoring were in group 1. Six patients had significant supraventricular arrhythmias, all well tolerated. Ambulatory monitoring revealed significant ventricular arrhythmias (modified Lown grade 2 or higher) in 39 patients, with a lower prevalence in group 1 (30% versus 48%, p = 0.05). No correlation was found between prevalence of ventricular arrhythmias and right ventricular systolic pressure, cardiopulmonary bypass duration, presence of a synthetic patch, previous pulmonary artery banding, presence of complete right bundle branch block and cardiomegaly on chest X-ray film. Prevalence of ventricular arrhythmias increased with follow-up duration, age at evaluation and age at surgery. These were always well tolerated and did not warrant treatment. Thus, right atriotomy reduces the prevalence of right bundle branch block but does not prevent late AV block. Ventricular arrhythmias are frequent after surgical closure of ventricular septal defect whatever the surgical approach and their prevalence is not statistically different from that in postoperative tetralogy of Fallot.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229772 TI - Efficacy of propafenone in preventing ventricular tachycardia: inverse correlation with rate-related prolongation of conduction time. AB - The efficacy of propafenone in preventing induction of ventricular tachycardia was evaluated in 25 consecutive patients (mean age 62 +/- 8 years) with remote myocardial infarction who underwent programmed electrical stimulation for ventricular arrhythmia using up to three extra-stimuli after basic drive at the right ventricular apex. In nine patients (Group A), propafenone prevented induction of sustained ventricular tachycardia (noninducible in four, nonsustained [less than 30 s] in five). In the other 16 patients (Group B), sustained ventricular tachycardia was still inducible; in 11 of the 16, the tachycardia configuration was unchanged but the cycle length was significantly longer (431 +/- 99 versus 284 +/- 44 ms, p less than 0.001). Propafenone did not significantly affect either sinus cycle length or AH and HV intervals. However, it prolonged QRS duration during sinus rhythm equally in both groups of patients. With ventricular pacing, propafenone also prolonged right ventricular effective and functional refractory periods and surface QRS duration. There was greater lengthening of the paced surface QRS duration when drug therapy was ineffective (for example, +35 +/- 12 ms in Group A versus +69 +/- 23 ms in Group B at a basic drive of 400 ms, p less than 0.01). Drug-induced prolongation of a paced QRS complex greater than 40 ms had a 94% positive predictive value for drug failure to prevent induction of ventricular tachycardia. Drug-induced percent prolongation of ventricular tachycardia cycle length in Group B did not correlate well with percent QRS prolongation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229773 TI - Sorting out the mechanisms of antiarrhythmic drug action. PMID- 2229774 TI - Surgical treatment of endomyocardial fibrosis: a new approach. AB - Endomyocardial fibrosis has been treated surgically for many years. For complete removal of fibrosis from both ventricles by the classic technique, each atrioventricular (AV) valve was removed and replaced with a prosthesis. Relapse of endomyocardial fibrosis has not been observed after surgical correction. Reoperations have been carried out because of complications of valve prostheses. A new surgical technique for removal of ventricular fibrous tissue with preservation of the mitral and tricuspid valves was used in nine consecutive patients with endomyocardial fibrosis. Initial results show a reduction of pulmonary hypertension, mean right and left atrial pressures and end-diastolic pressures in both ventricles. Tricuspid annuloplasty was performed in seven patients and mitral annuloplasty in five. No valve prosthesis was used. There was no death and New York Heart Association functional class improved from class III or IV in the preoperative period to class I or II in the postoperative period. These data suggest that resection of endocardial fibrous tissue can be indicated early in the clinical course and performed with preservation of the AV valves. PMID- 2229775 TI - Effect of intravenous streptokinase on the relation between initial ST-predicted size and final QRS-estimated size of acute myocardial infarcts. AB - Thrombolytic therapy has been documented to reduce acute myocardial infarct size. The previously established relation between initial ST segment elevation and final electrocardiographic (ECG) myocardial infarct size in patients without coronary reperfusion might therefore be altered by thrombolytic therapy. The effect of intravenous streptokinase on this relation was therefore studied in 73 patients with initial acute myocardial infarction who had participated in the Second International Study of Infarct Survival (ISIS-2). Patients who received streptokinase were considered as one group and patients who did not receive streptokinase as a control group. Final myocardial infarct size, which was estimated from the QRS score, was predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. In the 40 control patients there was no change from ST-predicted to final QRS-estimated infarct size (median 17.7% versus 18.3%; p = NS). In the 33 patients in the streptokinase group, there was a highly significant decrease from predicted to final myocardial infarct size (median 21.9% versus 16.2%; p less than 0.0002). This decrease was found for both anterior (median 23.7% versus 19.5%; p less than 0.03) and inferior (median 21.9% versus 12.0%; p = 0.001) infarct locations. Multiple regression analysis adjusting for differences in predicted infarct size confirmed the significance of streptokinase on the difference in infarct size (p = 0.006). Based on the variability of the percent change from predicted to final infarct size in the control group, a threshold decrease greater than or equal to 20% is required for identification of salvage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229776 TI - Intraoperative assessment of regional myocardial perfusion using quantitative myocardial contrast echocardiography: an experimental evaluation. AB - To test the hypothesis that myocardial contrast echocardiography can be used to quantitate regional myocardial flow in the arrested heart at the time of delivery of cardioplegic solution, data were acquired in 13 dogs on cardiopulmonary bypass. Different degrees of stenosis were placed in random order on the left anterior descending coronary artery. For each stenosis, myocardial contrast echocardiography was performed by injecting sonicated albumin microbubbles into the cross-clamped aortic root at the time of delivery of cardioplegic solution. The resultant echocardiographic images were analyzed on an off-line computer. Background-subtracted time-intensity plots were generated, and an exponential function, f(t) = Ce-alpha t + De- beta t, was applied to each plot. Variables that reflected the total number of microbubbles entering the coronary artery bed, such as the area under the curve and the peak height of the curve, correlated best with radiolabeled microsphere-measured myocardial flow (r = 0.92 and r = 0.91, respectively). Variables that reflected the appearance of contrast microbubbles in the myocardium, such as the initial slope and the slope at 1 s, also had a good correlation with myocardial flow (r = 0.84 and r = 0.89, respectively). Variables that reflected the washout of contrast medium from the myocardium, such as the slope of the descending portion of the curve, had only a fair correlation with myocardial flow (r = 0.65). In six dogs, the technique of injecting contrast medium into the cross-clamped aortic root was also examined. Although continuous infusion of contrast medium produced smaller perturbations in mean aortic and distal left anterior descending artery pressures compared with a bolus injection (p less than 0.01), the correlation between the variables of the time-intensity curves and flow was equally close with both techniques. It is concluded that it is possible to quantitate myocardial flow by using myocardial contrast echocardiography at the time of delivery of cardioplegic solution in dogs on cardiopulmonary bypass. The implementation of this technique in humans might be useful in guiding the sequence of graft placement and thereby improving myocardial preservation during coronary artery bypass operations. PMID- 2229777 TI - Prostaglandin modulation of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium chloride combined with efferent cardiac sympathetic stimulation in dogs. AB - Prostaglandins inhibit efferent cardiac sympathetic nerve effects by acting at presynaptic sites and may act to suppress some arrhythmias. In the present study, the effects of intravenous administration of prostacyclin (PGI2) and prostaglandin E2 (PGE2) on early afterdepolarizations and ventricular tachycardia induced by cesium chloride (0.5 mmol/liter per kg body weight intravenously) combined with stimulation of bilateral ansae subclaviae in anesthetized dogs were examined. The right atrium was paced at a constant cycle length of 600 ms. A left ventricular endocardial monophasic action potential catheter was used to detect early afterdepolarizations. Prostacyclin (0.2 microgram/kg per min) reduced the amplitude of the early afterdepolarizations (39.2 +/- 8.4% of the monophasic action potential amplitude during control study to 28.7 +/- 5.5%, n = 10; p less than 0.001) as well as the prevalence of ventricular tachycardia (11 of 14 dogs during control study to 5 of 14 dogs; p = 0.031). Prostaglandin E2 (0.2 to 0.6 microgram/kg per min) did not significantly reduce the early afterdepolarization amplitude (34.7 +/- 8.9% to 25.1 +/- 10.7%, n = 8; p = 0.085) or the prevalence of ventricular tachycardia (8 of 10 versus 6 of 10 dogs; p = 0.50). Alpha- and beta-adrenoceptor blockade with combined intravenous administration of propranolol (0.5 mg/kg) and phentolamine (0.3 mg/kg) decreased the amplitude of the early afterdepolarizations induced by cesium chloride and bilateral ansae subclaviae stimulation from 38.6 +/- 11.2% to 18.8 +/- 3.3% (n = 6; p = 0.005). Additional administration of PGI2 further reduced the early afterdepolarization amplitude from 18.8 +/- 3.3% to 9.8 +/- 4.8% (n = 6; p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229778 TI - Effects of calcium channel blockers on coronary vasoconstriction induced by endothelin-1 in closed chest pigs. AB - The purpose of this study was to determine the effects of endothelin-1 on the coronary vascular bed of closed chest pigs. Endothelin-1 (3 to 30 pmol/kg body weight) was selectively administered into the left anterior descending coronary artery. Coronary blood flow and epicardial vessel diameter were measured by quantitative arteriography. Arterial pressure increased after a 30 pmol/kg dose and heart rate was not changed. Coronary blood flow and vessel diameter of the left anterior descending artery significantly decreased by 74% and 32%, respectively (p less than 0.01 versus control) after the 30 pmol/kg dose, whereas these variables modestly decreased in the left circumflex artery. Endothelin-1 in doses of 10 to 30 pmol/kg produced electrocardiographic ST segment elevation associated with decreased oxygen saturation of coronary sinus venous blood. Endothelin-induced coronary vasoconstriction was significantly inhibited after treatment with intravenous diltiazem (0.2 mg/kg, n = 6) or nifedipine (0.1 mg/kg, n = 5), but not after vehicle administration (n = 4). This study demonstrates that intracoronary administration of endothelin-1 causes significant myocardial ischemia through coronary vasoconstriction, which is inhibited by a calcium channel blocker. The data suggest that calcium influx into the smooth muscle cells appears to be involved at least in part in the mechanism of endothelin induced coronary vasoconstriction in vivo. PMID- 2229780 TI - Balloon expandable stent implantation in stenotic right heart valved conduits. AB - Although valved conduits have been used successfully in severe forms of right ventricular-pulmonary artery discontinuity, progressive valved conduit stenosis is an important clinical problem. To determine the feasibility of reducing right heart valved conduit stenosis with a balloon expandable stent, a baboon model was used, in which the pulmonary artery was ligated and a right ventricular to pulmonary artery 14 mm bioprosthetic Dacron valved conduit implanted. In five baboons, at an average of 40 months after valved conduit implantation, fibrointimal stenosis at the valve site resulted in narrowing and a mean transconduit pressure gradient of 49 mm Hg (range 33 to 65). A tubular slotted steel stent (1.2 cm long) was deployed within the valved conduit after inflation of an 8 to 15 mm diameter balloon catheter that was introduced through the femoral vein. A stent was delivered to all valved conduits; however, in two baboons, balloon undersizing resulted in stent dislodgment. In the remaining three baboons, the transconduit gradient was reduced by 59% (49 to 20 mm Hg) and right ventricular systolic pressure decreased acutely by 35% (77 to 50 mm Hg). It is concluded that stent deployment is feasible in right ventricular to pulmonary artery stenotic valved conduits and may result in significant hemodynamic improvement. However, successful stent delivery is critically dependent on the proper selection of stent length and balloon diameter. PMID- 2229779 TI - Cardiac teratogenesis of trichloroethylene and dichloroethylene in a mammalian model. AB - Recent epidemiologic studies have demonstrated a greater than expected number of pediatric patients with congenital heart disease in areas where drinking water was contaminated by halogenated aliphatic hydrocarbons. Trichloroethylene, trichloroethane and dichlorethylene were the principal contaminants in the groundwater. A previous study of chick embryos demonstrated that when injected into the air sacs of fertilized eggs trichloroethylene produced more than three times the number of cardiac defects that are found in control embryos. This mammalian study demonstrates similar effects of trichloroethylene and dichloroethylene when applied under provocative circumstances (that is, solutions delivered through a catheter into the gravid uterus from an intraperitoneal osmotic pump) to the developing rat fetus in utero during the period of organ differentiation and development. Furthermore, the effect is dose dependent for both agents. Although only a very small number of congenital heart anomalies (3%) were found in the control group, 9% and 12.5% were found in the lower dose trichloroethylene and dichloroethylene groups and 14% and 21% in the higher dose groups, respectively (p less than 0.05). A variety of cardiac defects were found. Dichloroethylene appears to be at least as great a cardiac teratogen as trichloroethylene even though it was administered at a 10-fold lower concentration. These agents appear to be specific cardiac teratogens because only a single noncardiac anomaly was found. This study in a rat model demonstrates a dose-dependent relation between fetal exposure to trichloroethylene and dichloroethylene in utero during the period of organogenesis and the appearance of a variety of congenital cardiac defects. PMID- 2229781 TI - Direct visualization of ruptured chordae tendineae by transesophageal two dimensional echocardiography. AB - To determine the value of transesophageal echocardiography in the detection of ruptured chordae tendineae, 28 patients who had surgical therapy for pure mitral regurgitation were evaluated prospectively by conventional transthoracic and transesophageal two-dimensional echocardiography. Seventeen patients (Group I) had ruptured chordae tendineae and 11 (Group II) had intact chordae tendineae. Transthoracic echocardiography detected ruptured chordae tendineae in 6 patients from Group I (sensitivity 35%) and flail leaflets in 11 patients from Group I (sensitivity 65%). Transesophageal echocardiography disclosed ruptured chordae tendineae in all 17 Group I patients (sensitivity 100%); the sensitivity was significantly higher than that of transthoracic echocardiography. No abnormal chordal echoes were visualized in any patient from Group II by either transthoracic or transesophageal echocardiography (specificity 100%). Transesophageal echocardiography is a highly sensitive method for detecting ruptured chordae tendineae and is superior to transthoracic echocardiography in establishing its diagnosis. PMID- 2229782 TI - Transesophageal echocardiography to detect atrial clots in candidates for percutaneous transseptal mitral balloon valvuloplasty. AB - Left atrial thrombi are common in patients with mitral stenosis. When percutaneous balloon mitral valvuloplasty is performed on such patients, there is a potential risk of thrombus dislodgment and embolization. In this study conventional transthoracic echocardiography and transesophageal echocardiography were performed for percutaneous balloon mitral valvuloplasty on 19 consecutive candidates (6 men, 13 women, 23 to 81 years old). In five patients (26%), transesophageal echocardiography revealed a left atrial thrombus; in only one of these was there a suspicion of left atrial thrombus on transthoracic echocardiography. Balloon mitral valvuloplasty was canceled in four of the five patients. Three underwent mitral valve surgery that confirmed the echocardiographic findings. Transesophageal echocardiography is better than conventional transthoracic echocardiography in detecting left atrial clots in candidates for balloon mitral valvuloplasty. Because of the potential risk of embolization, transesophageal echocardiography is recommended in all candidates for balloon mitral valvuloplasty. PMID- 2229783 TI - Detection of restenosis after successful coronary angioplasty: improved clinical decision making with use of a logistic model combining procedural and follow-up variables. AB - A prospective study of 111 patients who underwent repeat coronary angiography and exercise thallium-201 scintigraphy 6 +/- 2 months after complete revascularization by percutaneous transluminal coronary angioplasty was performed to assess whether clinical, procedure-related and postangioplasty exercise variables yield independent information for the prediction of angiographic restenosis after angioplasty. Complete revascularization was defined as successful angioplasty of one or more vessels that resulted in no residual coronary lesion with greater than 50% diameter stenosis. Restenosis was defined as a residual stenosis at the time of repeat angiography of greater than 50% of luminal diameter. Restenosis occurred in 40% of the patients. The 111 patients were randomly subdivided into a learning group (n = 84) and a testing group (n = 27). A logistic discriminant analysis was performed in the learning group and the logistic model was used to estimate a logistic probability of restenosis. This probability of restenosis was validated in the testing group. In the learning group of 84 patients univariate analysis of 39 factors revealed 8 factors related to restenosis: recurrence of angina (p less than 0.0001), postangioplasty abnormal finding on exercise thallium-201 scintigram (p less than 0.0001), exercise thallium-201 scintigram score (p less than 0.0001), difference between exercise and rest ST segment depression (p less than 0.001), postangioplasty exercise ST segment depression (p less than 0.001), absolute postangioplasty stenosis diameter (p less than 0.003), postangioplasty exercise work load (p less than 0.03) and postangioplasty exercise heart rate (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229784 TI - Results of coronary surgery after failed elective coronary angioplasty in patients with prior coronary surgery. AB - The results of coronary artery bypass surgery after failed elective coronary angioplasty in patients who have undergone prior coronary surgery are unknown. Coronary angioplasty may be performed to relieve angina after surgery either to the native coronary vessels or to grafts. Failure of attempted coronary angioplasty may mandate repeat coronary surgery, often in the setting of acute ischemia. From 1980 to 1989, 1,263 patients with prior coronary bypass surgery underwent angioplasty; of these patients, 46 (3.6%) underwent reoperation for failed angioplasty during the same hospital stay. Of the 46 patients who underwent reoperation, 33 had and 13 did not have acute ischemia. In the group with ischemia, 3 patients (9.1%) died and 14 (42.4%) died or had a Q wave myocardial infarction in the hospital compared with no deaths (p = NS) and no deaths or Q wave myocardial infarction (p = 0.005) in the group without ischemia. At 3 years, the actuarial survival rate was 88 +/- 6% in the group with ischemia, whereas there were no deaths in the group without ischemia (p = NS), and freedom from death or myocardial infarction was 51 +/- 10% in the group with ischemia, versus no events in the group without ischemia (p = 0.006). In most patients with prior coronary bypass surgery, coronary angioplasty was performed without the need for repeat coronary bypass surgery. Should coronary angioplasty fail, reoperation in patients without acute ischemia can be performed with overall patient survival comparable to that of elective reoperative coronary bypass without coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229785 TI - Coronary angioplasty in patients with previous bypass surgery. PMID- 2229786 TI - Serial left ventricular performance evaluated by cardiac catheterization before, immediately after and at 6 months after balloon aortic valvuloplasty. AB - Although impaired ventricular function has been shown to improve after aortic valve replacement, there are few data on hemodynamic changes after balloon aortic valvuloplasty based on follow-up catheterization. Of 71 patients surviving 6 months after balloon aortic valvuloplasty, 41 agreed to late recatheterization. All patients had pre- and postvalvuloplasty and 6 month catheterization data measured with high fidelity micromanometer pressure recordings and simultaneous digital subtraction left ventriculography. The hemodynamic result immediately after valvuloplasty included a reduction in the aortic valve gradient and a moderate increase in aortic valve area (0.51 +/- 0.14 to 0.81 +/- 0.19 cm2, p less than 0.0001). Ejection fraction increased slightly (52 +/- 18 to 55 +/- 17%, p less than 0.0001) despite a decrease in peak positive rate of rise of left ventricular pressure (dP/dt 1,650 +/- 460 to 1,500 +/- 490 mm Hg/s, p less than 0.05). There was also a decrease in left ventricular afterload and a small decrease in preload. At 6 month recatheterization, the mean aortic valve gradient and area were similar to baseline values, with 31 (76%) of 41 patients demonstrating valvular restenosis. At 6 months many left ventricular hemodynamic variables, including peak positive dP/dt and stroke work, also resembled prevalvuloplasty values. However, left ventricular end-diastolic volume was reduced (111 +/- 40 ml at 6 months versus 136 +/- 52 ml before valvuloplasty, p less than 0.01). The mean left ventricular ejection fraction was unchanged from prevalvuloplasty values in the study group of 41 patients, but was significantly improved in 9 of 15 patients with a baseline ejection fraction less than 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229787 TI - Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries. AB - The causes of chest pain in patients found to have angiographically normal coronary arteries during cardiac catheterization remain controversial. Cardiac sensitivity to catheter manipulation, pacing at various stimulus intensities and intracoronary injection of contrast medium was examined in several groups of patients who underwent cardiac catheterization. Right heart (especially right ventricular) catheter manipulation and pacing and intracoronary contrast medium provoked chest pain typical of that previously experienced in 29 (81%) of 36 patients with chest pain and angiographically normal coronary arteries and 15 (46%) of 33 symptomatic patients with hypertrophic cardiomyopathy. In contrast, only 2 (6%) of 33 symptomatic patients with coronary artery disease experienced their typical chest pain with these sensitivity tests (p less than 0.001). None of 10 patients with valvular heart disease but without a chest pain syndrome experienced any sensation with these tests. Cutaneous pain threshold testing demonstrated that patients with chest pain and normal coronary arteries had a higher pain threshold to thermal stimulation compared with patients who had coronary artery disease or hypertrophic cardiomyopathy. No relation existed between cardiac sensitivity and cutaneous sensitivity testing. Thus, patients who have chest pain despite angiographically normal coronary arteries may have abnormal cardiac sensitivity to a variety of stimuli. This increased sensitivity may be of causal importance to their chest pain syndrome or may contribute to their perception of ischemia-induced pain. The same phenomenon was also commonly seen in symptomatic patients with hypertrophic cardiomyopathy. Whether this phenomenon represents abnormal activation of pain receptors within the heart or abnormal processing of visceral afferent neural impulses in the peripheral or central nervous system is unknown. PMID- 2229788 TI - Comparison of hemodynamic responses during dynamic exercise in the upright and supine postures after orthotopic cardiac transplantation. AB - Abnormal hemodynamic responses during supine exercise have been well documented in orthotopic cardiac transplant recipients. To determine the effect of posture, central hemodynamics were studied in 20 patients during a change from supine to sitting and during graded upright bicycle exercise (group U) and were compared with those of 20 patients matched for age, gender and time from transplantation who were studied after passive leg elevation and during exercise in the supine posture (group S). Passive leg elevation resulted in a 9% increase in stroke index (34 +/- 6 to 37 +/- 6 ml/m2, p less than 0.001) and a 10% increase in cardiac index (3.1 +/- 0.4 to 3.4 +/- 0.5 liters/min per m2, p less than 0.001) in group S patients compared with a 15% reduction in stroke index (34 +/- 7 to 29 +/- 6 ml/m2, p less than 0.001) and a 9% decrease in cardiac index (3.2 +/- 0.6 to 2.9 +/- 0.5 liters/min per m2, p less than 0.001) in group U patients on assuming the sitting posture. Likewise, both the pulmonary capillary wedge pressure and right atrial pressure increased significantly (13 +/- 4 to 17 +/- 8 mm Hg, p less than 0.001 and 5 +/- 3 to 7 +/- 3 mm Hg, p less than 0.001) with passive leg elevation in group S and decreased on sitting (12 +/- 6 to 8 +/- 5 mm Hg, p less than 0.001 and 5 +/- 3 to 3 +/- 2, p less than 0.001) in group U.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229789 TI - Single photon emission computed tomography with thallium-201 during adenosine induced coronary hyperemia: correlation with coronary arteriography, exercise thallium imaging and two-dimensional echocardiography. AB - The feasibility, safety and diagnostic accuracy of single photon emission computed tomography (SPECT) with thallium-201 imaging during adenosine-induced coronary hyperemia were evaluated in 53 patients with and 7 without coronary artery disease proved by coronary angiography. Adenosine was infused intravenously at a dose of 0.14 mg/kg body weight per min for 6 min and thallium was injected at 3 min. Adenosine caused an increase in heart rate (68 +/- 12 at baseline versus 87 +/- 18 beats/min at peak effect, p less than 0.0001) but no change in blood pressure. The sensitivity and specificity were 92% (95% confidence intervals 81% to 98%) and 100% (95% confidence intervals 59% to 100%), respectively; 20 (61%) of 33 patients with multivessel coronary artery disease were also correctly identified. In 30 patients, the predictive accuracy of adenosine thallium imaging was slightly higher than that of exercise SPECT thallium imaging (90% versus 80%, p = NS) (95% confidence intervals 72% to 97% and 61% to 92%, respectively). In 25 patients, two-dimensional echocardiography during adenosine infusion disclosed a new wall motion abnormality in 2 (10%) of 20 patients with coronary artery disease; 80% of these patients had reversible thallium defects (p less than 0.001). Side effects were mild and transient; aminophylline was used in only three patients. Thus, adenosine SPECT thallium imaging provides a high degree of accuracy in the diagnosis of coronary artery disease. The results are comparable with those of exercise SPECT thallium imaging. Most reversible defects in the adenosine study are not associated with any transient wall motion abnormality. PMID- 2229790 TI - Adenosine-thallium imaging: faster and better. PMID- 2229791 TI - Reduction of left ventricular preload by lower body negative pressure alters Doppler transmitral filling patterns. AB - The objective of this study was to evaluate the effect of alterations in preload induced by lower body negative pressure on Doppler transmitral filling patterns. Echocardiograms and Doppler recordings were performed in 18 normal young men (aged 23 to 32 years) during various levels of lower body negative pressure (0, 20 and -50 mm Hg). Lower body negative pressure induced a reduction in diastolic velocity integral (from 12.17 +/- 0.79 to 8.42 +/- 0.71 cm, p = 0.0067) and consequently left ventricular diastolic diameter (from 5.11 +/- 0.09 to 4.45 +/- 0.1 cm, p less than 0.0001). There was a significant reflex increase in heart rate from 59.9 +/- 1.9 to 77.1 +/- 2.4 beats/min (p less than 0.0001), but blood pressure was unchanged. This reduction in preload altered Doppler transmittral filling patterns as follows: 1) peak early velocity (E) decreased from 59.2 +/- 3.8 to 39.1 +/- 1.7 cm/s (p less than 0.0001); 2) atrial filing velocity (A) was unchanged (35.58 +/- 1.5 to 33.52 +/- 1.4 cm/s, p = 0.517); 3) E/A ratio decreased from 1.7 +/- 0.13 to 1.19 +/- 0.08 (p = 0.0087); 4) mean acceleration (from 482 +/- 37 to 390 +/- 27 cm/s2, p = 0.03) and mean deceleration (from 327 +/- 31 to 169 +/- 21 cm/s2, p less than 0.001) of the early filling wave were significantly reduced; and 5) peak acceleration (from 907 +/- 42 to 829 +/- 29 cm/s2) and peak deceleration (from 771 +/- 94 to 547 +/- 76 cm/s2) also decreased, but not significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229792 TI - Instantaneous and continuous cardiac output in humans obtained with a Doppler pulmonary artery catheter. AB - A new Doppler pulmonary artery catheter was used to measure instantaneous and continuous cardiac output in both an in vitro model and in 44 patients undergoing cardiac catheterization. Cardiac output was calculated with use of the Doppler catheter-determined instantaneous space-average velocity and the ultrasonically determined instantaneous vessel area. Doppler flow and thermodilution were compared with electromagnetic flow in the in vitro model and with Fick cardiac output in patients. Doppler catheter-determined flow was highly predictive of electro-magnetic flow in the pulsatile flow model (r = 0.99, slope [m] = 1.01 and SEE = 0.05) and appeared comparable to thermodilution measurements (r = 1.00, m = 1.03 and SEE = 0.02). In patients undergoing cardiac catheterization, Doppler catheter-determined cardiac output appeared to modestly underestimate Fick cardiac output (r = 0.82, m = 0.80 and SEE = 0.09; mean error +/- SEM = -0.26 +/- 0.14 liters/min). However, predictive accuracy was comparable to simultaneously obtained thermodilution measurements (r = 0.85, m = 1.07 and SEE = 0.10; mean error +/- SEM = 0.61 +/- 0.16 liters/min). This new Doppler catheter system utilizes multiple ultrasound transducers to provide angle-independent measurements of vessel diameter and instantaneous velocity within the main pulmonary artery, resulting in a more accurate assessment of Doppler-derived cardiac output. In addition, useful information concerning hemodynamic variables such as peak flow, acceleration, deceleration, stroke work and pulmonary impedance may be derived. PMID- 2229793 TI - Termination of acute atrial fibrillation in the Wolff-Parkinson-White syndrome by procainamide and propafenone: importance of atrial fibrillatory cycle length. AB - The effects of intravenous procainamide (n = 30) or propafenone (n = 25) were evaluated in 55 patients with acute atrial fibrillation and the Wolff-Parkinson White syndrome. All patients received either procainamide (12 to 15 mg/kg body weight) or propafenone (1 to 2 mg/kg) during sustained (greater than 10 min) atrial fibrillation or after termination of nonsustained atrial fibrillation. Termination of atrial fibrillation was attributed to a drug if it occurred less than or equal to 15 min after infusion. Measurements included mean cycle length of fibrillatory electrograms (mean AA interval) as measured at the high right atrium and shortest RR interval between pre-excited cycles during atrial fibrillation. Atrial fibrillation terminated more frequently after procainamide administration (65%) than after propafenone (46%), although this difference was not significant. Procainamide prolonged the shortest pre-excited RR interval (228 +/- 41 to 339 +/- 23 ms, p = 0.0001) as did propafenone (215 +/- 40 to 415 +/- 198 ms, p = 0.0001) and the magnitude of increase was greater for propafenone (p = 0.048). Patients with sustained atrial fibrillation had shorter mean AA intervals than did their counterparts with nonsustained atrial fibrillation (123 +/- 25 versus 186 +/- 35 ms, p = 0.0001). Termination of sustained atrial fibrillation by either drug was accompanied by prolongation of the mean AA interval but not necessarily by the shortest pre-excited RR interval. Termination of atrial fibrillation was heralded by a 68% increase in the mean AA interval after procainamide administration compared with a 30% increase when the arrhythmia persisted. For propafenone the increases were 90% and 68%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229794 TI - Feasibility and cost savings of outpatient electrophysiologic testing. AB - The feasibility of outpatient electrophysiologic testing was examined by reviewing 100 consecutive outpatient tests performed in 95 patients. Seventy-one of the patients (75%) had no underlying heart disease. The electrophysiologic tests were performed to evaluate supraventricular tachycardias (n = 47), nonsustained ventricular tachycardia (n = 20), unexplained syncope (n = 21), palpitation (n = 9) or intermittent heart block (n = 2). A mean of 2.8 +/- 0.5 6F electrode catheters were inserted through a femoral vein. An electrode catheter was inserted into a subclavian or internal jugular vein in 28 tests and a 5F cannula was inserted into a femoral artery to monitor the blood pressure in 20 tests. The results of 61 tests (61%) were abnormal. Patients were monitored for a mean of 3.8 +/- 1.2 h after the procedure and then discharged. No complications occurred. For cost analysis a subgroup of 60 of these patients was matched for age, gender, heart disease and indication for electrophysiologic testing with a group of 60 patients who underwent electrophysiologic testing as inpatients. Physicians' fees for the two groups were similar; however, the mean hospital charge was $5,845 +/- 3,763 for the inpatient group compared with only $2,120 +/- 1,244 for the outpatient group (p less than 0.001). Thus, outpatient electrophysiologic testing is feasible and safe and results in substantial cost savings in patients without life-threatening arrhythmias. PMID- 2229796 TI - Coronary artery plaque morphology after balloon angioplasty. PMID- 2229795 TI - Plaque morphology and pathologic changes in arteries from patients dying after coronary balloon angioplasty. AB - Morphologic correlates of pathologic success or failure were studied at autopsy in 28 patients with 40 coronary arteries that had been subjected to balloon angioplasty. The presence of the following histologic features was evaluated: plaque concentricity or eccentricity, calcification, fibrous or fibropultaceous plaque, medial disruption, luminal thrombus and inflammation. Angioplasty was considered successful (residual cross-sectional luminal area greater than 25%) on pathologic examination in 14 arteries and unsuccessful in 26 arteries. Eccentric plaques were more likely to be successfully dilated than were concentric lesions (p less than 0.05). Six (50%) of 12 fibropultaceous plaques were successfully dilated compared with only 8 (29%) of 28 fibrous plaques. Moderate to severe calcification did not preclude morphologic success. Medial stretching or dissection, or both, was more often associated with a successful result. Thus, plaque morphology may be an important determinant of pathologic outcome after coronary angioplasty. PMID- 2229797 TI - Coronary morphology after percutaneous directional coronary atherectomy in humans: autopsy analysis of three patients. AB - The morphologic basis of angiographically successful percutaneous directional atherectomy and subsequent restenosis in human coronary arteries is unknown. The clinical and pathologic features of three patients who died after coronary atherectomy are described. Tissue fragments obtained with atherectomy demonstrated atheromatous and fibroproliferative intima, media and adventitia. At autopsy, treated vascular segments (from the left anterior descending artery in two patients and a vein graft in one patient) demonstrated discrete defects in the vascular wall. Defects extending into atheroma, media or adventitia corresponded with the presence of these tissues in the atherectomy specimens. Tissues were otherwise not disrupted in the manner associated with balloon angioplasty. Acute mural thrombus deposition was evident in the resection zone in one patient. Late findings included fibroproliferative intimal tissue extending from the resected areas into the vascular lumen. In one patient intimal hyperplasia was sufficient to narrow the vascular lumen by 82% and was implicated in subsequent myocardial ischemia and infarction. The study indicates that 1) the vascular injury associated with atherectomy is distinct from that associated with balloon angioplasty, 2) acute mural thrombus deposition may occur even with resection limited to the intima, and 3) intimal hyperplasia may develop in regions treated with atherectomy and may be associated with late myocardial ischemia and infarction. PMID- 2229798 TI - Intracardiac shunting in children with ventricular septal defect: evaluation with Doppler color flow mapping. AB - In children with a ventricular septal defect, transseptal blood flow has been demonstrated angiographically to be bidirectional in all but the smallest defects. To investigate this phenomenon noninvasively, two-dimensional Doppler color flow echocardiography was used in 77 patients (aged 1 day to 15.5 years, mean 24 months). During isovolumetric contraction, flow was seen from the left to the right ventricle in 82 (98%) of 84 studies. During isovolumetric relaxation, right to left flow was noted in 72 (96%) of 75 studies. During early diastole in patients with an isolated defect, flow was initially from the right to the left ventricle and subsequently reversed to become left to right in 29 (91%) of 32 studies. In patients with concomitant right ventricular volume overload, flow across the ventricular defect was from the right to the left ventricle throughout diastole in 30 (86%) of 35 studies. In each of four patients with d-transposition of the great vessels and each of two patients with 1-transposition of the great vessels, blood flow was from the morphologic left ventricle to the morphologic right ventricle during isovolumetric contraction and from the morphologic right ventricle to the morphologic left ventricle during isovolumetric relaxation. These results demonstrate 1) the complex nature of intracardiac shunting in children with ventricular septal defect as previously shown by angiography; 2) an intrinsic functional difference in the contractile and relaxation properties of the morphologic left and right ventricles; and 3) differences in diastolic blood flow patterns between children with an isolated defect and those with a ventricular septal defect and right ventricular volume overload (p = 0.0001). PMID- 2229799 TI - Relation between color Doppler-detected directional flow in a ventricular septal defect and frame rate. PMID- 2229800 TI - Results of the arterial switch operation in patients with transposition of the great arteries and abnormalities of the mitral valve or left ventricular outflow tract. AB - Between January 1983 and October 1989, 290 patients underwent an arterial switch operation for transposition of the great arteries; 30 (10.3%) of the patients had abnormalities of the left ventricular outflow tract or mitral valve, or both. These abnormalities included isolated pulmonary valve stenosis (n = 9), septal (dynamic) subpulmonary stenosis (n = 5), anatomic (fixed) subpulmonary stenosis (n = 7), abnormal mitral chordae attachments (n = 2) or a combination of abnormalities (n = 7). There were two early deaths, one of which was due to previously unrecognized mitral stenosis and a subpulmonary (neo-aortic) membrane and one late death due to presumed coronary obstruction. Of the nine patients with pulmonary valve abnormalities due to either a bicommissural (n = 5) or a thickened tricommissural (n = 4) valve, only one underwent valvotomy. Peak systolic ejection gradients in these nine patients measured preoperatively ranged from 0 to 50 mm Hg. At follow-up study 5 to 30 months postoperatively, the neo aortic valve gradient was less than or equal to 15 mm Hg in all patients; three patients had mild neo-aortic regurgitation. Preoperative gradients may overestimate the degree of obstruction because of the increased pulmonary blood flow present in transposition. No patient with "dynamic" subpulmonary obstruction before the arterial switch operation had a surgical procedure performed on the left ventricular outflow tract; none had evidence of subaortic obstruction after the arterial switch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229801 TI - Long-term follow-up of patients after transcatheter direct current ablation of the atrioventricular junction. AB - The long-term follow-up study (41 +/- 23 months) of 47 patients undergoing direct current ablation because of drug-resistant supraventricular arrhythmias is reported. Significant early complications occurred in four patients and included hypotension, pericarditis, nonsustained polymorphic ventricular tachycardia and one sudden death. In 42 patients (86%), complete atrioventricular (AV) block was initially achieved. During the follow-up period, AV conduction resumed in 2 of these 42 patients. Of the seven patients in whom ablation was unsuccessful, two developed late complete AV block and three had symptomatic improvement. An improved activity level was reported among 83% of the patients with successful ablation. Health care utilization manifest as the number of hospital admissions per year before and after ablation decreased significantly after ablation (2.4 +/ 2.0 versus 0.3 +/- 0.5, p less than 0.001). Echocardiographic evaluation in five patients with a depressed left ventricular ejection fraction (27 +/- 7%) before ablation showed a significant increase (45 +/- 14%, p less than 0.05) after an average follow-up period of 31 months. New onset of congestive heart failure occurred after ablation in four patients, of whom two had no structural heart disease. The total mortality rate, including the one patient with sudden death, was 17% and was significantly higher among patients with underlying structural heart disease. Transcatheter direct current ablation is an effective treatment in patients with drug-resistant supraventricular tachycardia, providing a beneficial long-term outcome including an improved quality of life and a decrease in health care utilization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229802 TI - Effect of cocaine on the coronary circulation and systemic hemodynamics in dogs. AB - This study investigated the effect of intravenous cocaine (0.5 to 2 mg/kg body weight) on the coronary circulation and systemic hemodynamics in closed chest sedated dogs. The role of alpha- and beta-adrenoceptor stimulation in mediating these effects was also investigated. Cocaine produced dose-dependent increases in mean arterial pressure and rate-pressure product. Although the lower doses of cocaine had no significant effect on the coronary circulation, the 2 mg/kg dose produced a 55 +/- 14% increase in coronary vascular resistance (p less than 0.05 versus baseline) and a 19 +/- 3% reduction in diameter of the left anterior descending coronary artery (p less than 0.05 versus baseline). Despite these potentially deleterious effects on the coronary circulation (occurring at a time of markedly increased myocardial oxygen demand), the electrocardiogram did not demonstrate ischemic changes and there was no myocardial lactate production. Cocaine-induced coronary vasoconstriction was abolished by pretreatment with the alpha-adrenoceptor antagonist phentolamine, but not by pretreatment with the beta adrenoceptor antagonist propranolol. The findings that cocaine did not change systemic vascular resistance in dogs without adrenergic blockade, reduced systemic vascular resistance in dogs after alpha-blockade (p less than 0.05) and increased systemic vascular resistance in dogs after beta-blockade (p = 0.06) suggest that epinephrine (rather than norepinephrine) is primarily responsible for the peripheral vascular actions of cocaine. Thus, in this canine preparation with normal coronary arteries, cocaine produced vasoconstriction of both epicardial and coronary resistance vessels that was not associated with evidence of myocardial ischemia. The pharmacologic mechanism for the effect of cocaine on the coronary circulation is alpha-adrenoceptor stimulation, whereas systemic hemodynamic effects are mediated by combined alpha- and beta-adrenoceptor stimulation. PMID- 2229803 TI - Dissociation of changes in cardiovascular mass and performance with angiotensin converting enzyme inhibitors in Wistar-Kyoto and spontaneously hypertensive rats. AB - The effects of angiotensin-converting enzyme inhibitors on cardiovascular mass and function were measured in three groups of 22 week old male Wistar-Kyoto normotensive and spontaneously hypertensive rats treated with CGS-16617, cilazapril or quinapril. Left ventricular performance was assessed by electromagnetic flow meter during rapid whole blood infusion before and after arterial pressure and increased abruptly with aortic snare; aortic distensibility also was assessed in vitro. The systemic hemodynamic effects of these three agents were similar, yet their structural effects varied. Although left ventricular and aortic masses diminished and right ventricular mass remained unchanged (with all three agents) in the spontaneously hypertensive rats, CGS 11617 and cilazapril also reduced left ventricular mass in the normotensive Wistar-Kyoto rats without changing aortic mass. All three agents improved aortic distensibility whether or not mass was decreased. Left ventricular structural changes were associated with variable changes in pumping ability. These data show that reduced mass associated with angiotensin-converting enzyme inhibitor treatment was not consistent in ventricles and aorta, that a dissociation exists between structural and functional changes and that reduction of cardiac mass alone does not relate to changes in chamber mass or in function. Thus, biologic and pharmacodynamic differences exist among angiotensin-converting enzyme inhibitors as well as between classes of antihypertensive agents. PMID- 2229804 TI - ACC agenda update. PMID- 2229805 TI - Circulating heart-reactive antibodies in patients with myocarditis or cardiomyopathy. AB - Heart-reactive antibodies are commonly observed in patients with myocarditis or cardiomyopathy. Such antibodies may be important in the pathogenesis of these disorders, yet the specific antigens recognized have not been studied systematically. This report characterizes circulating heart autoantibodies from patients with myocarditis (n = 17) or idiopathic cardiomyopathy (n = 71) and from healthy volunteers (n = 15). Indirect immunofluorescence demonstrated that high titer (greater than or equal to 1:20) immunoglobulin G (IgG) antibody activity occurred in 59% of the myocarditis samples, 20% of the cardiomyopathy samples and none of the normal samples. All samples were tested by Western immunoblotting for IgG activity against a normal human heart extract. The number of antigens recognized by each sample was enumerated and the molecular weight of each antigen estimated; the prevalence of reactivity against antigens in selected molecular weight classes was determined. There was no difference in the mean number of heart antigens recognized by serum from each group. For most weight classes, prevalence either did not differ significantly among the various groups or subgroups or was greatest among samples from healthy volunteers. Prevalence of reactivity with 190 to 199 kilodalton (kd) antigens was greatest (p less than 0.05) among low titer serum samples from patients with myocarditis. High titer cardiomyopathy serum differed from normal serum by an increased (p less than 0.05) prevalence of antibodies to 40 to 49 and 100 to 109 kd antigens. These results suggest that western immunostaining may ultimately contribute substantively to identifying patients with myocarditis or cardiomyopathy. PMID- 2229806 TI - Diagnostic value of a new myocardial perfusion agent, teboroxime (SO 30,217), utilizing a rapid planar imaging protocol: preliminary results. AB - Technetium-99m-labeled agents have advantages over thallium-201 in terms of photon statistics, cost and clinical availability. They have been suggested as an alternative to thallium for myocardial perfusion imaging. Teboroxime is a new boronic acid adduct of technetium dioxime (BATO) compound that demonstrates favorable characteristics in preliminary studies. With use of a novel (seated) patient positioning technique and a rapid dynamic acquisition protocol, 30 patients underwent planar imaging with teboroxoime while at rest and after maximal treadmill exercise. Postexercise scans were completed in an average time (mean +/- SD) of 4.4 +/- 1.6 min, with 4.8 +/- 1.5 min for the views at rest. These results were compared with coronary arteriography or thallium scintigraphy after treadmill exercise, or both. Diagnostic agreement (abnormal versus normal) was present in 28 of the 30 patients (p less than 0.001). Regarding physiologic assessment as compared with thallium scintigraphy, the finding of infarction and ischemia was concordant in 89% and 86% of patients, respectively. This report describes the initial use of teboroxime with a rapid dynamic planar imaging technique, resulting in a high correlation with exercise thallium scintigraphy. Delayed postexercise images obtained 5 to 10 min after exercise demonstrated rapid disappearance of exercise-induced defects noted on the initial (0 to 5 min) postexercise views. The rapid differential washout with teboroxime has not been previously described and the possible clinical significance is discussed. PMID- 2229807 TI - Occupational asthma from vegetable gums. PMID- 2229808 TI - Cat skin as an important source of Fel d I allergen. AB - It is generally recognized that cat skin is an important extrasalivary source of the major cat allergen, Fel d I. Nevertheless, since cat saliva is readily applied to the skin during grooming, we tried to demonstrate that Fel d I can accumulate on cat skin without licking. Eight adult female cats were used. On day 0, two separate sites of the trunk were shaved and a 6 cm2 area in each site was washed three times with 5 ml of distilled water. The first and third washes were collected and stored for assay. The areas were then covered with an occlusive dressing. Twenty-four hours later, the site was washed once and the sample stored. On day 7, washes were collected as on day 0, and a collar was attached to the neck to prevent contamination from saliva. A single wash was done 24 hours later. Comparison of data was achieved with an analysis of variance. Repeated washes significantly reduced Fel d I levels from 35 +/- 21 to 10 +/- 9 mU/cm2 on day 0 (p less than 0.01) and from 36 +/- 18 to 12 +/- 7 mU/cm2 on day 7 (p less than 0.01). Fel d I levels increased significantly after 24 hours of occlusion from 10 +/- 9 to 41 +/- 24 mU/cm2 (p less than 0.01) and collar wearing from 12 +/- 7 to 54 +/- 21 mU/cm2 (p less than 0.001). These findings demonstrate that Fel d I is produced by cat skin. Mean daily production of Fel d I by cat skin is estimated to be 36 units. Cat skin is an important extrasalivary source of Fel d I. PMID- 2229809 TI - Acute hemorrhagic edema of infancy (AHEI)--a variant of Henoch-Schonlein purpura or a distinct clinical entity? AB - Acute hemorrhagic edema of infancy (AHEI) is an acute cutaneous leukocytoclastic vasculitis (LCV) of infants. The clinical picture has a violent onset with a short benign course followed by spontaneous complete recovery. We report 12 infants with AHEI who were studied clinically, serologically, and immunohistologically. Edema and palpable purpuric skin lesions were present in all infants who were in good general condition. Serologic studies were unremarkable. Light microscopic examination of the skin biopsy specimens revealed LCV as in Henoch-Schonlein purpura (HSP). Direct immunofluorescent study revealed depositions of various immunoreactants, including fibrinogen, C3, IgG, IgM, IgA, and IgE (100%, 100%, 22%, 78%, 33%, and 33%, respectively) in the wall and around the small vessels. Similar deposition of Clq was also present in three infants in whom Clq could be studied (100%). The clinical similarities and differences between AHEI and HSP have been discussed in the literature. AHEI is observed before 2 years of age and is confined to the skin. The skin lesions of HSP are more polymorphic. Although histopathologic findings are similar, the immunohistologic pattern found in our series of AHEI is rather different from the pattern of HSP. Taking all of these findings into account, we suggest that AHEI should be considered as a separate, clinicopathologic entity or a possible variant of HSP. The more descriptive term "acute benign cutaneous LCV of infancy" is offered for this clinicopathologic entity. PMID- 2229810 TI - Role of nasal allergy in chronic maxillary sinusitis--diagnostic value of nasal challenge with allergen. AB - The role of nasal allergy in chronic maxillary sinusitis without an air-fluid level was studied in 37 patients. Seventy-three nasal provocation tests with various inhalant allergens were performed in 37 patients by means of rhinomanometry, and maxillary sinus radiographs were performed before and repeatedly after the allergen challenge. Forty-one positive nasal responses (NRs) occurred in 29 patients; 13 were immediate only, 18 were late only, and 10 NRs were dual responses. Of these responses, 32 demonstrated radiographic changes, primarily an increase in mucosal edema and/or opacification. These responses were accompanied by increased pressure in the maxillary sinuses, acute headache, and sometimes otalgia. Eight patients did not develop any NRs; however, increased thickening of the mucosal membrane of the maxillary sinuses, accompanied by subjective symptoms, was recorded in three of these nonresponders. These results demonstrate the role of nasal allergy in some patients with chronic maxillary sinusitis, which may affect the diagnostic and therapeutic approaches to this disorder. PMID- 2229811 TI - Suppression of mouse IgE response by immune complexes. AB - The effect of antibodies alone or complexed to antigen on an IgE response was compared in mice immunized with a low dose of antigen. The results demonstrated that immune complexes (ICs) at equivalence were more efficient than antibodies in promoting a suppression of this response when they were injected simultaneously or before, but not after, the antigen. This effect was dose dependent, antigen specific, and long lasting. Furthermore, only isologous ICs were suppressive. ICs prepared with IgG1 antibodies were more effective than ICs prepared with IgG2. Digestion of the Fc fragment of the antibody eliminated completely the suppressive action of antibodies alone, but not of ICs. These results indicate that, whereas an Fc-dependent mechanism is responsible for the effect of antibodies, an additional mechanism is also operating in suppression induced by ICs. PMID- 2229812 TI - Characteristics of patients with food-related complaints. AB - Forty-five patients with classic food-allergic symptoms and/or subjective food related complaints not traditionally associated with food allergy underwent evaluation. On the basis of a comprehensive clinical history, skin testing, and placebo-controlled, double-blind food challenges, patients were assigned to one of two groups: patients with reactions highly suggestive of IgE-mediated food hypersensitivity (group A, N = 22) and patients with atypical adverse food reactions that could not be confirmed by double-blind food challenge (group B, N = 23). Most patients in both groups were female, 77.3% and 91.3% of patients in group A and B, respectively. In group B, onset of symptoms occurred at an older age than in group A, 28.9 years +/- 17.2 versus 17.1 +/- 12.1 (p = 0.0015), respectively, and involved more foods, 25.6 +/- 22.1 versus 5.2 +/- 5.5 (p = 0.0002). Foods causing most prominent symptoms among patients in group A included legumes, tree nuts, crustaceans, and fish. In group B, milk, white sugar, wheat, egg, smoked/cured meat, and yeast were among the most troublesome foods. All but one patient in group A gave a positive skin test response to food; only four patients in group B had a positive response. We conclude that a subset of patients with food-related complaints can be accurately predicted to have a negative double-blind challenge with suspected foods on the basis of information obtained by history and skin testing. PMID- 2229813 TI - Elevated serum interleukin-6 associated with a failure in B cell differentiation in common variable immunodeficiency. AB - Interleukin-6 (IL-6/B cell stimulatory factor 2) has been found to drive activated human B-lymphocytes through the final stages of differentiation to become immunoglobulin-producing cells. Most patients with common variable immunodeficiency (CVI) have B-lymphocytes that fail to differentiate into high rate immunoglobulin-secreting cells in vivo and in vitro. In view of (1) the known effects of IL-6 to promote B-lymphocyte terminal differentiation and (2) the defect in differentiation in B-lymphocytes of patients with CVI, we believed that it was important to analyze the role of this cytokine in patients with CVI. Using an IL-6-dependent murine hybridoma cell line in a bioassay, serum IL-6 levels were determined in 17 patients with CVI and in eight normal control subjects. Thirteen of the 17 patients with CVI exhibited serum IL-6 levels that were twofold to 18-fold higher than the range (mean, +2 SD) of normal control subjects. Spontaneous IL-6 production by peripheral blood mononuclear cells (PBMC) of patients with CVI was significantly higher than that from normal control subjects, whereas lipopolysaccharide maximally stimulated IL-6 production by PBMCs of patients with CVI or PBMCs of normal control subjects was equivalent. A substance inhibitory of IL-6 bioactivity was found in equivalent amounts in sera of both patients and normal control subjects. Sera from patients with CVI with high IL-6 bioactivity were found to have saturated this IL-6 inhibitory substance, thus resulting in large amounts of free IL-6 in the sera. These studies suggest that the failure of B cells from patients with CVI to terminally differentiate into high-rate immunoglobulin-secreting cells cannot be attributed to a decrease in the serum levels of IL-6 and that the increased circulating IL-6 levels in patients with CVI result from hyperproduction rather than decreased use of IL-6. The persistently elevated levels of IL-6 observed in some patients with CVI may secondarily result in the induction of the neoplastic and autoimmune phenomena associated with this disease. PMID- 2229815 TI - Prevalence of occupational asthma and immunologic sensitization to guar gum among employees at a carpet-manufacturing plant. AB - Guar gum is a high-molecular-weight agent that can cause occupational rhinitis and asthma. We surveyed the employees at a carpet-manufacturing plant in which guar gum is used to adhere the dye to the fiber; 162/177 of the employees (92%) participated in the first part of the survey that included a questionnaire and skin prick tests with common allergens and guar gum (1 mg/ml). IgE and IgG antibodies to guar gum were also measured in those subjects (133/162 or 82%) who agreed to blood tests. Thirty-seven subjects (23%) had a history suggestive of occupational asthma and 59 (36%), of occupational rhinitis. Eight subjects (5%) demonstrated immediate skin reactivity to guar gum. Eleven subjects (8.3%) had serum IgE antibodies to guar gum. All subjects, except one subject who had a history suggestive of occupational asthma (n = 37) or positive skin tests (n = 4), participated in the second part of the study. A methacholine-inhalation test was performed during a workshift or in the 3 to 4 hours after the workshift. Five subjects had a concentration of methacholine causing a 20% fall in FEV1 of less than 16 mg/ml (significant bronchial hyperresponsiveness) and positive skin reactions to guar gum. Four of these subjects underwent specific inhalation challenges. The remaining subject had a history of severe bronchospastic reaction on exposure to guar gum, and his FEV1 of 1.6 L made specific challenges impossible. Two subjects had typical isolated immediate reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229814 TI - Immunoblot analysis of sera from patients with allergic bronchopulmonary aspergillosis: correlation with disease activity. AB - Immunoblot analysis was used to evaluate the IgG, IgE, and IgA responses to Aspergillus fumigatus antigen with the sera of five patients with allergic bronchopulmonary aspergillosis (ABPA) before, during, and after suspected exacerbation of their disease. The results revealed a heterogenous antibody response, unique for each patient, to specific Aspergillus fumigatus antigens that correlated with the molecular weights of previously well-characterized antigens of importance in the immunopathogenesis of ABPA. A rating scale was devised for measuring band intensity that allowed the patient's antibody responses to be reproducibly semiquantitated. Immunoblot analysis demonstrated qualitative and semiquantitative information that is not available with other in vitro assays used in the study of patients with ABPA, such as ELISA. These initial results emphasize the need for additional evaluation of this technique to assess its potential clinical application in this disease. PMID- 2229816 TI - Chronic urticaria exacerbated by the antioxidant food preservatives, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). AB - Two patients with chronic idiopathic urticaria in whom remissions were achieved with dye- and preservative-elimination diet had exacerbations of their urticaria when they were challenged under double-blind, placebo-controlled conditions with butylated hydroxyanisole and butylated hydroxytoluene. After elimination of butylated hydroxyanisole and butylated hydroxytoluene from their diets, there was marked abatement of the frequency, severity, and duration of their urticaria. These antioxidants appear capable of aggravating symptoms in certain patients with chronic urticaria. PMID- 2229817 TI - Different prevalence and degree of nonspecific bronchial hyperreactivity between seasonal and perennial rhinitis. AB - From the patients observed at our respiratory allergology service, we selected patients with rhinitis only, without any past or present respiratory symptoms, for our study. All these patients had normal pulmonary function, were administered carbachol or methacholine bronchial challenges, and had one or more skin reactions to perennial or seasonal allergens. Patients were allocated to three groups: group A, patients with seasonal rhinitis who were administered nonspecific challenges out of season; group B, patients with seasonal rhinitis tested during the season; and group C, patients with perennial rhinitis. The three groups were divided into subgroups according to the duration in years of rhinitis and to the degree of nonspecific bronchial responsiveness. The distribution into four groups of reactivity, arbitrarily defined as normal and mildly, moderately, and severely increased reactivity, was as follows: group A, 124, 21, 30, 22; group B, 75, 15, 7, and 21: and group C, 69, 17, 39, and 72, respectively. The patients of group C (perennial rhinitis) demonstrated a distribution significantly (p less than 0.001) different from subjects with seasonal rhinitis, both group A and group B. Our results are consistent with the hypothesis that perennial rhinitis is much more important than seasonal rhinitis as a risk factor for developing nonspecific bronchial hyperresponsiveness. PMID- 2229818 TI - How should we use skin testing to quantify IgE sensitivity? PMID- 2229819 TI - Immunotherapy decreases skin sensitivity to ragweed extract: demonstration by midpoint skin test titration. PMID- 2229820 TI - Histamine and disease: a forum on current and future management. Carlsbad, California, August 25-26, 1989. Proceedings. PMID- 2229821 TI - Mast cell biology. AB - Mast cells are the repository for histamine in the body. They influence the pathophysiology of allergic diseases, such as rhinitis, urticaria, and asthma; regulate bone formation and integrity; help repair and maintain connective tissue; promote wound healing; and probably contribute to the development and preservation of the endothelium and small blood vessels. Although they are found in all human tissue, mast cells are most prevalent at the interface between the host and its environment, that is, in the skin and in the mucosa of the upper and lower respiratory tracts and the gastrointestinal tract. Recent evidence suggests that two types of mast cells exist: (1) the connective tissue type, found primarily but not exclusively in loose connective tissue and skin, and (2) the mucosal type, found primarily in gastrointestinal mucosa and peripheral airways. The factors that produce this differentiation are not fully known. Although both mast cell types have IgE receptors that can be activated by allergens, differences between the two types exist in their responses to nonallergic signals, the mediators they release, their proteoglycan constituents, and the makeup of their granular enzymes. The importance of these biochemical differences to cellular functioning remains to be investigated. PMID- 2229822 TI - Tryptase, a mediator of human mast cells. AB - Tryptase, a mediator secreted by human mast cells during immediate reactions, has demonstrated effects on several pathways in vitro. This enzyme can rapidly inactivate fibrinogen and, as a complex with heparin, may prevent coagulation that may otherwise occur when plasma enters tissues at sites of immediate reactions. Tryptase may also activate prostromelysin, which in turn activates latent collagenase. When canine pulmonary smooth muscle is incubated with canine tryptase, the contractile response to histamine is increased. Tryptase, quantifiable in complex biologic fluids by immunoassay, can serve as a specific indicator of mast cell involvement in certain clinical settings. For example, after bee sting--induced anaphylaxis, tryptase levels in the blood peak at approximately 1 hour, then decline with a half-life of approximately 2 hours. Additionally, elevated tryptase levels in bronchoalveolar lavage fluid of asymptomatic, atopic persons with asthma suggest ongoing mast cell activation, which may relate to adenosine hyperresponsiveness and a persistence of bronchial hyperreactivity. Tryptase levels in bronchial lavage fluid of atopic patients with asthma rise markedly after endobronchial allergen challenge but not after an exercise challenge, suggesting a lack of mast cell involvement in the latter condition. PMID- 2229823 TI - Performance effects of antihistamines. AB - In 1988 an estimated 30 million Americans spent more than $500 million for single entity antihistamines. Classic first-generation antihistamines, which are available without prescription, can cross the blood-brain barrier and have been reported to produce various central nervous system effects. Sedation, the most common adverse effect of these agents, occurs in 10% to 25% of antihistamine users. Drowsiness has been attributed to the blockade of central histaminergic receptors; antagonism of other brain receptors, such as serotonergic, cholinergic, and central alpha-adrenergic receptors, has also been proposed. The newer second-generation H1-receptor antagonists are typically large, lipophobic molecules with a charged side chain and are extensively bound to albumin. Consequently, these agents have difficulty entering the brain, and they appear no more likely to induce sedation than does placebo. The effects of antihistamines on psychomotor reflexes and driving, antihistamine-induced drowsiness, and interaction of antihistamines with alcohol and tranquilizers have been studied with numerous methodologies. The centrally acting first-generation agents commonly cause greater performance decrements as compared with the newer, nonsedating, second-generation antihistamines. PMID- 2229824 TI - Neuropeptides and nasal secretion. AB - Recent research has disclosed that neurotransmitters and neuropeptides released within the autonomic nervous system exert homeostatic control of nasal secretion. Although cholinergic and adrenergic influences have long been thought to be the predominant mechanisms, the nonadrenergic, noncholinergic responses may have more suitable, longer-lasting effects. Peptides from sensory nerves, such as calcitonin gene related peptide, substance P, and neurokinin A, may participate in axon response-mediated vasodilation and plasma extravasation. Substance P and gastrin releasing peptide may induce glandular secretion. Defensive responses to local mucosal injury may be amplified by axon response, which initiates these vascular and glandular reactions. Cholinergic effects are primarily responsible for mediating parasympathetic reflexes, but vasoactive intestinal peptide may regulate acetylcholine release, augment glandular secretory responses, and have a vasodilatory effect. In the sympathetic nervous system, neuropeptide Y probably functions as a long-acting vasoconstrictor. Integration of sympathetic and parasympathetic influence may regulate the normal nasal cycle, and sensory and parasympathetic defensive reflexes may respond to epithelial and mast cell stimulation. It is possible, then, that the pathophysiology of vasomotor rhinitis involves an exaggeration of these neural influences. PMID- 2229825 TI - The role of antihistamines in upper respiratory tract infections. PMID- 2229826 TI - The role of antihistamines in otitis. AB - Chronic and recurrent otitis media can manifest as otitis media with effusion. Both infection and eustachian tube obstruction (ETO) have been found to play an important role in its pathogenesis. ETO can be demonstrated during both early- and late-phase reactions in patients with allergic rhinitis after intranasal challenge with an allergen. Intranasal challenge with either histamine or prostaglandin D2 also provokes ETO, with the latter mediator perhaps more potent than the former. Middle ear effusions from patients with chronic or recurrent otitis media have been found to contain dramatically increased concentrations of histamine relative to the concentrations in their plasma. The development of nasal and eustachian tube obstruction in allergic rhinitis patients has been prevented by pretreatment with an antihistamine plus decongestant before intranasal challenge with pollen allergen. Investigations are currently under way to assess the effect of antihistamine pretreatment on nasal and eustachian tube obstruction in patients undergoing intranasal histamine challenge. PMID- 2229827 TI - Mast cells and histamine in asthma. PMID- 2229828 TI - Predictive value of airway reactivity. PMID- 2229830 TI - Blockage of a "nonspecific" provocational challenge as a model for predicting clinical efficacy. PMID- 2229829 TI - Patterns of airway responsiveness. PMID- 2229831 TI - The use of provocational challenge in office practice. PMID- 2229832 TI - The role of antihistamines in the treatment of chronic urticaria. AB - For many years, H1 antihistamines have been the primary management option for urticaria. However, undesirable side effects, particularly daytime sedation, have limited the usefulness of these classic antihistamines. A new class of peripherally acting, nonsedating antihistamines (e.g., terfenadine, astemizole, loratadine, and cetirizine) has proved to have clinical efficacy comparable with the classic antihistamines. In comparative trials between the various nonsedating agents, no significant difference in efficacy has been noted. All these agents have good safety profiles, although astemizole use has been correlated with increased appetite and weight gain in some patients, and cetirizine has caused slightly increased sedative effects compared with placebo. Although H1/H2 antihistamine combinations have been proposed as possible treatments for urticaria, studies have produced mixed results. PMID- 2229833 TI - Mechanisms involved in allergic contact dermatitis. AB - Allergic contact dermatitis is a common inflammatory skin disease caused by agents such as plants, chemical compounds, and topical medications. Histologic features typically include edema within the epidermis and dermis and a lymphohistiocytic infiltrate with an admixture of basophils. Langerhans cells and keratinocytes play pivotal roles in allergic contact dermatitis reactions. Langerhans cells synthesize and express class II molecules that allow the presentation of exogenous antigens to T lymphocytes. Additionally, keratinocytes and Langerhans cells produce interleukin-1, which is thought to be a second signal that activates T cells. Mast cells and basophils also may play a proinflammatory role. Treatment primarily consists of removal of the offending agent. At times, systemic corticosteroids may be required, especially in the acute phase. In more chronic cases, topical corticosteroids may be beneficial. Antihistamines may be useful because of their soporific effects, but their usefulness is limited. PMID- 2229834 TI - The role of antihistamine therapy in vascular headaches. AB - Migraine (vascular) headache is a complex syndrome that involves vascular hyperreactivity. The functions of systemic mediators in migraine are not fully understood. It is unclear which mediators provoke this probably atopic disorder and which represent an attempt to correct an imbalance. However, it has been demonstrated fairly conclusively that increased histamine levels correlate with migraine attacks in susceptible persons. Recent studies showing that histamine seems to have many different receptors and to adopt different conformations for different receptors may serve as a useful guide to future scientific investigation. Further impetus may come from ongoing studies of H3 histamine receptors, which indicate that H3 agonists offer promise as prophylactic agents for people who suffer from vascular headaches. PMID- 2229835 TI - Arthritis and mast cell activation. AB - The significance of the mast cell in the pathogenesis of rheumatic diseases continues to receive attention. Increased numbers of mast cells are found in the synovial tissue and fluid of patients with inflammatory arthritides, and these mast cells can be activated by many of the substances found in inflammatory synovial fluid. This activation results in the release of mediators that are capable of amplifying the inflammatory process within the joint space. Recent research has shown that mast cells also produce a variety of cytokines and hematopoietic growth factors that may have paracrine and autocrine functions that are important to the development of the inflammatory cell infiltrate. Increased numbers of mast cells are also found in many fibrotic conditions, including scleroderma. These mast cells, directly or through mediator generation, affect the function of endothelial cells, fibroblasts, and growth factors important to the proliferation and function of these cells. A clearer understanding of mast cell involvement in the inflammatory arthritides and fibrotic processes should lead to new therapeutic strategies. PMID- 2229836 TI - Bioaerosols: prevalence and health effects in the indoor environment. AB - Assessing the role of bioaerosols in residence-related symptoms involves (1) determining that symptoms are related to the residence by medical examination and careful questioning, (2) connecting reported symptoms with known or hypothesized effects of bioaerosols, (3) examining the residence for bioaerosol risk factors such as overcrowding/poor ventilation, inappropriate outdoor air intrusion, and dampness/standing water, (4) and finally, if no obvious risk factors are present, air sampling. Air sampling should always be a last resort and should use a reliable volumetric method. Particulate samplers, such as the Burkard personal spore trap, are inexpensive alternatives to viable particle samplers and will provide data on most organisms implicated in hypersensitivity diseases. Interpretation of residential bioaerosol sample data requires both qualitative and quantitative comparison with adjacent outdoor air and examination of aerosol changes related to domestic activities. Recommendations that should lead to a decrease in indoor bioaerosols include the use of air conditioning to allow limitation of outdoor aerosols, prevention of dampness or moisture intrusion, and discouraging the use of humidifying devices other than steam. Bioaerosol assessment in the workplace is often more complex than for residences. Because the symptomatic subjects are not in charge of the environment, such situations often lead to difficult employee/management relations and occasionally to litigation. It is essential that each step in workplace bioaerosol assessment be defensible and that the best possible methods are used. The approach is similar to the approach used for residences, but on a larger scale. Symptom assessment must include stress and ergonomic factors. Air sampling, if this is necessary, must usually be extensive with controls for ventilation rates, occupancy, and spatial variation. PMID- 2229837 TI - Immunotherapy abrogates the generation of eosinophil and neutrophil chemotactic activity during pollen season. AB - In a group of 40 birch pollen-allergic patients with a history of rhinoconjunctivitis and wheezing during the pollen season, 20 were immunotherapy (IT) treated preseasonally with birch-pollen extract (Pharmacia, Uppsala, Sweden). Blood samples for determination of the levels of heat-labile eosinophil chemotactic activity (HL-ECA), heat-labile neutrophil chemotactic activity (HL NCA), and heat-stable neutrophil chemotactic activity were collected before the season, at the beginning of the study, at the start of the season, at the peak, at the end, and after the birch-pollen season. The symptoms from rhinoconjunctivitis and airways, peak expiratory flow, and use of medication were recorded throughout the season. Significant increases of HL-ECA and HL-NCA were observed in untreated compared with IT-treated patients at the start of the season (p less than 0.0001 for both activities) and at the peak of the birch pollen season (p less than 0.0005 and p less than 0.01, respectively). At the end of the season, HL-ECA levels were not significantly different between the patient groups, whereas HL-NCA levels were still higher in untreated patients (p less than 0.005). We conclude that IT completely abrogates the generation of HL-ECA and HL-NCA during a pollen season. PMID- 2229838 TI - Allergens as proteases: an Aspergillus fumigatus proteinase directly induces human epithelial cell detachment. AB - Allergic bronchopulmonary aspergillosis (ABPA) is characterized by pulmonary and systemic allergic and inflammatory processes triggered by fungal antigens. Airway damage is a feature of this disorder, and although Aspergillus-derived proteinases have been described, the capacity of Aspergillus, however, to directly induce damage to human epithelium has not previously been studied. We therefore cultured Aspergillus fumigatus from two patients with ABPA, extracted mycelial products by sonication and filtration, and then evaluated their capacity to induce epithelial cell (EC) desquamation from basement membrane using an in vitro model that uses intact human amniotic EC and native basement membrane. A. fumigatus extracts induced detachment of EC in a dose-dependent fashion, producing up to 34% +/- 6% detachment (p less than 0.05 compared to medium alone). Enzyme analysis of A. Fumigatus extract using synthetic substrates revealed the presence of a number of different enzymes; therefore, studies with specific proteinase inhibitors were undertaken to identify the proteinase(s) responsible for detachment. A. Fumigatus-induced desquamation was partially inhibited by phenylmethylsulfonylfluoride and substantially inhibited by glutathione and N-acetylcysteine, but not by alpha 1-antitrypsin, 1,10 phenanthroline, ethylenediaminetetraacetic acid, aprotinin, or soybean trypsin inhibitor at concentrations that inhibit other serine- or metalloproteinases. Gel filtration of the extract with a Sepharose 6B column revealed that the major epithelium-detaching activity appeared in the 20 to 35 kd fraction. Comparison with proteinase standards suggested a role for a chymotrypsin-like proteinase. Thus, A. fumigatus releases a proteinase that is directly able to induce EC detachment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229839 TI - It is children with atopic dermatitis who develop asthma more frequently if the mother smokes. AB - We elicited symptoms of atopic dermatitis (AD) and of asthma from 620 children who were themselves nonsmokers, were aged 1 to 17 years, and had been consecutively referred to an allergy clinic. A histamine bronchial-challenge test revealed bronchial hyperresponsiveness in 95% of the children who had a history of wheezing or asthma and who could perform the test reliably, indicating that most of them did indeed have asthma. Children with a history of AD were much more likely to have asthma if the mother was a smoker than if she was a nonsmoker (79% versus 52%; p = 0.001). Similarly, if AD was found on examination, the percentages with asthma were 74% and 44%, respectively. By contrast, the children with no history of AD had asthma as frequently if the mother was a nonsmoker (42%) as when she was a smoker (40%). In children with AD, the prevalence of asthma was greater in both boys and girls when the mother was a smoker, but only in boys when the father was a smoker. Multiple logistic regression confirmed that the risk of asthma was greatly increased when the child had both AD and a mother who smoked. PMID- 2229840 TI - Salsalate cross-sensitivity in aspirin-sensitive patients with asthma. AB - Ten aspirin (ASA)-sensitive patients with asthma underwent double-blind, placebo controlled oral challenges with salsalate followed by ASA-sensitive confirmatory challenges. All 10 patients sustained asthmatic reactions to ASA, but only two developed respiratory reactions to 2 gm of salsalate. In these two patients, repeat confirmatory challenges with 2 gm of salsalate reproduced the same asthmatic reactions. Both patients were desensitized to ASA, and cross desensitization with 2 gm of salsalate was then achieved. We conclude that salsalate, a weak inhibitor of cyclooxygenase in vitro, is less likely than ASA to induce asthma in known ASA-sensitive patients with asthma but may occasionally cross-react in these patients. Such reactions were mild and easily treated with beta 2-agonists. PMID- 2229841 TI - Immediate skin test reactivity to Food and Drug Administration-approved standardized extracts. AB - In an effort to determine whether recently introduced Food and Drug Administration-approved standardized extracts produce clinically appropriate responses in a population, 200 subjects were skin prick tested (SPT). Thirteen extracts (10 pollens, two house dust (HD) mites and cat) were tested in three groups of subjects, 50 with a history of asthma or allergic rhinitis (AL), 50 without asthma or perennial or seasonal allergic rhinitis but with a positive immediate family history for these conditions (FAL), and 100 subjects without a personal or family history for these conditions (NAL). An SPT mean wheal diameter greater than or equal to 3 mm was considered positive. Ninety percent (95% confidence interval [CI], 82% to 98%) of AL subjects had at least one positive SPT. Forty-six percent of FAL subjects (95% CI, 30% to 58%) and 29% of NAL subjects (95% CI, 20% to 38%) had at least one positive SPT. More FAL than NAL subjects had at least one SPT (p less than 0.05), and FAL subjects had more positive SPTs than NAL subjects (p less than 0.05), further supporting the genetic regulation of allergen-specific IgE production. Of the five AL subjects with no SPT wheal greater than or equal to 3 mm, three subjects were available for intradermal tests. Thirteen nonstandardized allergens similar to allergens used for SPT were applied intradermally in each of these three subjects and were all negative. Compared with history, an SPT wheal greater than or equal to 3 mm to cat produced a sensitivity of 0.90, a specificity of 0.90, and diagnostic accuracy of 0.90. Tenfold dilutions of pollens and cat reduced sensitivity without significantly improving specificity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229842 TI - The Hymenoptera venom study. III: Safety of venom immunotherapy. AB - One thousand four hundred ten (44%) of the 3236 subjects in the Hymenoptera venom study accepted venom immunotherapy (VIT). Time to maintenance averaged 95 days, and the largest number achieved maintenance (147 subjects, 10.4%) at day 56. Ninety-two percent of the treated subjects achieved maintenance, and 84% continued therapy, most subjects (91%) until the study was terminated. One hundred seventy-one subjects (12%) experienced 327 treatment systemic reactions (Srs). The incidence of pruritus and angioedema/urticaria was similar with mild, moderate, or severe SRs. The SR severity did not correlate with the severity of the most recent sting before entry into the Hymenoptera-venom study, the most severe historical sting SR, the most severe SR during venom skin tests, the total dose of venom, the degree of skin test reactivity, or the lowest concentration yielding a positive skin test. Most SRs occurred between 1 and 50 micrograms and at maintenance; honeybee or wasp venoms were most likely to produce SR. This study, the largest of its kind with the use of standardized extracts, demonstrates (1) that there was good compliance, (2) that various historical and diagnostic criteria did not predict SRs to VIT, (3) that SRs to VIT were most likely to occur between 1 and 50 micrograms and at maintenance, (4) that honeybee or wasp venoms were most likely to produce an SR, and (5) that VIT is relatively safe. PMID- 2229843 TI - Identification and characterization of important cockroach allergens. AB - Allergens extracted from American and German cockroach species have been identified as significant sensitizing agents in the induction/exacerbation of asthma. In the present study, gel-filtration fractions of saline extracts of American cockroach (Periplaneta americana) whole bodies (AWBE fraction 2) and German cockroach (Blattella germanica) whole bodies (GWBE fraction 2) were used to identify and characterize important cockroach allergens by immunoprinting. In addition, allergens from AWBE and GWBE fractions 2 were additionally fractionated by chromatofocusing on polybuffer exchanger. Immunoprinting studies demonstrated several important acidic allergens in cockroach whole body extracts. All but one allergen had an acid isoelectric point (pH 2.80 to 5.20). Two allergens, one that focused at pH 3.50 and another allergen (or group of isoallergens) that focused between pH 4.15 to 4.55 were reactive with most sera obtained from cockroach sensitive subjects. Chromatofocusing and subsequent skin test and RAST studies of AWBE and GWBE confirmed the presence of significant cockroach allergens with isoelectric points within the zone of pH 3.75 to 4.50. RAST-inhibition studies demonstrated the similarity of these allergens between AWBE and GWBE. Collectively, these observations identify the presence of several acidic cockroach allergens presumably shared between AWBE and GWBE. PMID- 2229844 TI - The control of house dust mite allergens in rugs. AB - Used rugs were vacuum cleaned, "wet cleaned," "shampooed," or heated in an autoclave. The effects on the live-mite population, on the allergen (Dermatophagoides pteronyssinus, Der p I and Der p II; and Dermatophagoides farinae, Der f II) content, and on the suitability of the rugs as a habitat for house dust mites was studied. Autoclaving was most effective in all three aspects. The cleaning methods were quite inefficient for killing the mites, but a significant reduction of allergens and deterioration of the habitat quality was established. "Wet cleaning" appears particularly promising. PMID- 2229845 TI - Measurement of histamine in nasal lavage fluid: comparison of a glass fiber-based fluorometric method with two radioimmunoassays. AB - The determination of histamine in nasal secretions and nasal lavage fluid may be of importance to monitor activation of histamine containing cells in the nasal cavity. However, such studies have been besieged by controversy, specifically to findings of changes in histamine levels in relation to allergenic stimulation. This controversy may be due to the specificity and accuracy of the various methods used to determine histamine in the nasal fluid. We have therefore applied and compared three new methods to determine histamine in nasal lavage fluids obtained before and after allergen challenge in normal subjects and patients with allergic rhinitis. We used a fluorometric glass fiber-based histamine method (FHR) and two RIAs, I and II. The FHR (detection limit, 7.0 nmol) and the RIA II (detection limit, 0.2 nmol) are specific for histamine itself, whereas the RIA I (detection limit, 18.0 nmol) measures mainly methylhistamine and cross-reacts to some extent with histamine. The histamine levels in the nasal lavage fluids from the nasal challenges demonstrated histamine values between 100 and 2000 nmol/L of histamine with significantly higher levels in the postallergen challenges for the allergic subjects as compared to the normal control subjects. The FHR correlated well with the RIA I and RIA II methods with correlation coefficients of 0.77 to 0.88 (p less than 0.001), respectively. However, the RIA I (methylhistamine antibody) always demonstrated absolute histamine values 5% to 20% of values measured by the RIA II (at the level of cross-reactivity to histamine).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229847 TI - Opportunities for research-oriented dietitians. PMID- 2229846 TI - Down regulation in hypersensitivity pneumonitis. AB - Levels of soluble interleukin-2 receptor (sol-IL-2R) in the bronchoalveolar lavage fluid (BALF) of pigeon breeders with hypersensitivity pneumonitis were compared with BALF levels in asymptomatic pigeon breeders who had been exposed to pigeon allergens for an equivalent length of time. No mean difference in sol-IL 2R levels was detected when these levels were expressed per milliliter BALF, epithelial lining fluid, or per T-lymphocyte. In sarcoidosis, the availability of sol-IL-2R per T cell was significantly higher for the group with inactive sarcoidosis compared with the group with active sarcoidosis. The results do not support the hypothesis that down regulation, in subjects exposed to allergens causing hypersensitivity pneumonitis, is a function of cell-free sol-IL-2R levels in BALF. In the dynamic situation, however, the hypothesis appears tenable. PMID- 2229848 TI - Credentials and skills required for hospital food and nutrition department directors. AB - The perceptions of hospital administrators, food and nutrition department directors, and management dietetic educators were compared with respect to the credentials and administrative skills required for a director of a food and nutrition department in a hospital with 300 beds or more. Questionnaires were mailed to the director of food and nutrition services and the vice president of hospital operations at 132 hospitals in five midwestern states. Fifty-six questionnaires were mailed to all educators on the 1986 to 1988 membership list of the Foodservice Systems Management Education Council. Response rates of directors, administrators, and educators were 68%, 53%, and 82%, respectively. The questionnaire consisted of three parts. Part one addressed credentials required; part two required participants to rank 14 skill categories in order of importance; and part three focused on facility descriptors and credentials of participating administrators and directors. Findings of the survey indicate that the minimum qualifications for department directors were registered dietitian status, at least a bachelor's degree in food and nutrition, and work experience in foodservice systems management. Although administrators ranked foodservice management skills higher than nutrition skills, they ranked nutrition skills significantly (p less than .001) higher than did directors or educators. These findings may guide career development of practitioners who aspire to department director positions. PMID- 2229849 TI - Contributions of food groups to intakes of energy, nutrients, cholesterol, and fiber in women's diets: effect of method of classifying food mixtures. AB - This study examined the effect of using two different methods for categorizing food mixtures when calculating the contribution of various food groups to energy, macronutrient, cholesterol, and fiber intakes. Using method 1, each food mixture was classified as a single item and assigned to a food group according to its main ingredient. Using method 2, most of the food mixtures were separated into their constituent ingredients, and each ingredient was assigned to its appropriate food group. Data were from 1,032 women who provided at least 4 days of dietary data in the U.S. Department of Agriculture's 1985 Continuing Survey of Food Intakes by Individuals. We found that the importance of each food group's contribution to individual dietary components varied depending on the method used to categorize the food mixtures. When food mixtures were separated into their constituent ingredients before assigning foods to food groups, the contributions of meat, fish, poultry, and grain products declined for each of the seven dietary components studied. At the same time, the contributions of milk products, fats, and oils increased for most of the seven components. The results highlight the importance of foods eaten as part of food mixtures to the intake of energy, macronutrients, cholesterol, and fiber. PMID- 2229850 TI - Dietary selenium intakes and plasma selenium concentrations of formula-fed and cow's milk-fed infants. AB - The plasma selenium concentrations of 57 infants 8 to 12 months of age were assessed using flameless atomic absorption spectrophotometry. The infants ingested either cow's milk or whey-predominant milk-based infant formula as their primary beverage as part of a mixed diet for at least 3 months. The calculated mean +/- standard deviation (SD) daily dietary selenium intake of 26 infants fed cow's milk (34 +/- 13 micrograms), assessed by a 3-day diet record and/or a 24 hour diet recall, was significantly (p less than or equal to .001) greater than that of 31 formula-fed infants (22 +/- 11 micrograms). The mean +/- SD plasma selenium concentration of infants fed cow's milk (39 +/- 11 micrograms/L) was also significantly (p less than or equal to .05) greater than that of infants fed formula (31 +/- 12 micrograms/L). Both groups of infants ingested similar amounts of total energy; however, the infants fed cow's milk received more total protein and selenium and a greater percentage of protein and selenium from their primary beverage than did the infants receiving formula. Both groups of infants were consuming a mixed diet with similar sources of selenium. To examine the selenium status of infants as well as other individuals better, further analysis of foods is clearly needed to provide more information on dietary selenium sources. The influence of variables such as body size and ethnicity, intake, sources and forms of dietary protein, and dietary forms of selenium on plasma selenium concentrations must also be investigated. PMID- 2229851 TI - Folate status of adolescents: effects of folic acid supplementation. AB - This study was designed to determine the folate status of an adolescent population and to demonstrate the effect of folic acid supplementation on subjects with low folate status. In phase one, folate status was evaluated in a biracial sample of 164 adolescents 12 to 15 years old. Socioeconomic, demographic, anthropometric, and 7-day food record data were collected, and serum and erythrocyte folate levels were determined. Thirty-five adolescents considered to have had low folate status 6 months earlier participated in phase two, a 2 month supplementation period and reevaluation. No racial differences were observed in folate status, as indicated by amount of folate in the blood and diet. Boys had significantly (p less than .05) higher folate levels in serum and erythrocytes than did girls. Thirteen percent of the boys and 40% of the girls were folate deficient as judged by amount of erythrocyte folate less than 317 nmol/L (140 ng/mL). The folate-deficient subjects had significantly (p less than .05) lower values of hemoglobin than did the normal subjects. Seventeen percent of the boys and 42% of the girls had folate intakes below the recommended dietary allowance for folate. Supplementation of 400 micrograms folic acid daily for 2 months resulted in significant (P less than .05) increases in serum folate, erythrocyte folate, and hemoglobin values and a decrease in mean corpuscular volume. Evidence of high prevalence of low folate status, positive relationship between erythrocyte folate and hemoglobin, and responses of hemoglobin and mean corpuscular volume to the supplement indicated that folate consumption may not be optimal in some groups of adolescents, especially in girls. PMID- 2229852 TI - The effects of moderate exercise training on nutrient intake in mildly obese women. AB - The relationship between moderate exercise training (five 45-minute sessions per week, brisk walking at 62 +/- 2% VO2 max for 15 weeks) and changes in nutrient intake was investigated in a group of 36 sedentary, mildly obese women. The study was conducted using a 2 x 3 factorial design (two groups of subjects: exercise and nonexercise groups; three periods: baseline, 6-week, and 15-week testing sessions). Data were analyzed using repeated measures ANOVA. The pattern of change in caloric intake over time tended to be different between groups (F[2, 68] = 2.50, p = .089); the exercise group experienced a significant decrease in caloric intake by 15 weeks. Significant group x time interactions were found for intakes of carbohydrate, dietary fiber, thiamin, niacin, vitamin B-6, and folate. Intake tended to decrease in the exercise group and to increase in the nonexercise group. Change in intake of each of these nutrients was significantly correlated with change in bread and cereal consumption. The pattern of change in bread and cereal intake over time was significantly different between groups (Pillais Trace = 0.266, F[2, 33] = 5.99, p = .006); the exercise group had significant decreases in intake at 6 and 15 weeks vs baseline values. These data suggest that mildly obese women reduce energy intake subsequent to initiating an exercise program; concomitantly there is a decrease in the quality of nutrient intake from their diets compared with those of sedentary controls. PMID- 2229853 TI - An interdisciplinary nutrition assessment and intervention protocol for children with disabilities. AB - Because of the multifactorial nature of the nutrition problems associated with developmental disabilities, a well-organized, interdisciplinary effort is necessary to deal with such problems. A team composed of professional and support staff, the client, and the family needs to be involved in an integrated approach to service. The team members share their knowledge and expertise in developing an individual program plan to meet identified needs. This article describes the development and implementation of a prototype for interdisciplinary nutritional evaluation and intervention in an outpatient setting. In 1987, a Regional Nutrition and Feeding Diagnosis and Evaluation Clinic was established through a contractual agreement between the University of Georgia University Affiliated Program and St. Mary's Hospital in Athens, GA. The purposes of the clinic are twofold: to offer direct services to developmentally disabled infants and children who require outpatient services and to provide a unique community-based interdisciplinary training experience for graduate students in nutrition and other health disciplines. The interdisciplinary treatment protocol is based on current knowledge in the treatment of developmental disabilities. PMID- 2229855 TI - Diet quality and the eating environment of preschool children. PMID- 2229854 TI - A review of iodine toxicity reports. AB - This article summarizes case reports, population studies, and experimental studies from the literature concerning adverse effects of exposure to iodine from the mid-1880s to 1988. Exposure to excessive iodine through foods, dietary supplements, topical medications, and/or iodinated contrast media has resulted in thyroiditis, goiter, hypothyroidism, hyperthyroidism, sensitivity reactions, or acute responses for some individuals. Reports of maternal iodine exposure during pregnancy or lactation affecting newborn or nursing infants are cited. Susceptibility to excess iodine is discussed as well as the relationship between dose and response. It is concluded that some individuals can tolerate very high levels of iodine with no apparent side effects and that iodine intakes less than or equal to 1.000 mg/day are probably safe for the majority of the population, but may cause adverse effects in some individuals. Determination of maximum tolerable levels of iodine intake will require human experimental studies at levels between 0.150 and 1.000 mg/day for normal subjects, subjects with autonomous thyroid tissue, and iodine-sensitive subjects. PMID- 2229856 TI - Family physicians' opinions on nutrition after nutrition education. PMID- 2229857 TI - Members honored as Medallion Award winners in Denver on October 16. PMID- 2229858 TI - Nutrition labeling: issues and directions for the 1990s. AB - This report will become a part of the comment and rule-making process that FDA and USDA will conduct to achieve food and nutrition labeling reform. The agencies have requested interested parties to comment on the report's recommendations. The report will be of interest to Congress in developing legislative proposals to clarify the legal basis for anticipated reforms. For the food industry, health professionals, and consumer groups, it will be of interest in terms of their own objectives in promoting nutrition labeling changes that are in line with current dietary recommendations and in product development. Dietitians will want to comment on the recommendations in the Institute of Medicine report and on provisions of the proposed regulations. Dietitians should encourage their elected officials in Congress to support legislation for food labeling reform. PMID- 2229859 TI - The Senior Care Study. A controlled trial of a consultative/unit-based geriatric assessment program in acute care. AB - Successful models of inpatient geriatric assessment have often involved long hospital stays, specialized interdisciplinary care, and prolonged follow-up, which are difficult to achieve within a prospective payment system. A randomized clinical trial was undertaken to evaluate the efficacy (maintenance or improvement in mental, emotional, and physical function) of using a geriatric assessment process in acute hospital care without increasing hospital charges or lengths of stay. Four hundred thirty-six patients greater than or equal to 75 years of age were randomly allocated to treatment (n = 221) or control (n = 215) conditions. Patients in the treatment group were admitted to a special unit and evaluated on admission by an interdisciplinary team, which developed a care plan. Although primary care was provided by the patient's own physician, the team followed the patients as consultants on the unit in the hospital, and by telephone for 2 months after discharge. The control group was placed on other units and received usual hospital care. The treatment and control groups were similar at study entry. At follow-up, there were no significant differences between the groups with respect to lengths of stay, hospital charges, mortality, change in physical function, or change in mental function. The treatment group changed more often in measured emotional function (chi 2 = 6.213, P = .045). This study indicates that it is feasible to implement consultative interdisciplinary team care in the acute-care hospital, but that its efficacy may be limited when applied to an unselected group of older patients. PMID- 2229860 TI - The Senior Care Study. The optimal use of medications in acutely ill older patients. AB - Geriatric assessment units have improved pharmacotherapy for their patients by decreasing the number of medications prescribed. The Senior Care Study, a randomized controlled trial, compared a multidisciplinary-team approach to patient care to the standard medical practice of the institution. As a part of the trial, the effectiveness of an interdisciplinary team intervention in improving the use of medications was studied. Study goals were to decrease medications used, decrease unnecessary medications, and improve medication choices in our acutely ill inpatient population. A pharmacist interviewed all experimental patients and patient records, and presented medication concerns and recommendations at a team conference. MEDICATIONs were counted on admission and on the third day, sixth week, and third month after randomization. MEDICATIONs were paired with patient problems. MEDICATION: problem pairs were judged as inappropriate choices if there were potential side effects that would affect patient function, and if better alternatives were available. The 215 control and 221 experimental patients in the study were similar in age, sex, place of origin, and number of medications on admission. Experimental patients took fewer medications than controls on the third day (5.3 versus 5.9, P less than .05). Experimental patients received fewer multiple unpaired medications (11% versus 19%, P less than .025) and fewer inappropriate medication choices (20% versus 37%, P less than .005). The results suggest that the team intervention was effective in improving pharmacotherapy in the acute-care setting. PMID- 2229861 TI - Cognitive function testing in comprehensive geriatric assessment. A comparison of cognitive test performance in residential and clinic settings. AB - Tests of cognitive function are frequently used in geriatric assessment, but the effect of test setting has rarely been explored. To determine the effect of testing site on the performance of elderly patients undergoing a comprehensive geriatric assessment, we administered the Mini-Mental State Exam to 116 geriatric patients in the clinic and at their residence. Their cognitive abilities varied from normal to severely impaired. The patients' scores were 1.5 +/- 3.6 (mean +/- SD) higher at their residence. The clinical importance of a difference in score of 1.5 is not clear. For this reason a second analysis was performed in which a difference in scores of five points or greater between settings was considered clinically meaningful. Twenty-five percent (29 of 116) differed by five points or more. Of these 29 patients, 22 (76%) tested better in the residential setting. These differences were statistically significant (P = .001). We conclude that the testing site may affect test performance and that in-home assessment may reveal the optimal cognitive function of geriatric patients. PMID- 2229862 TI - Reference values for the Mini-Mental State Examination (MMSE) in octo- and nonagenarians. AB - The Mini-Mental State Examination (MMSE) was used in a population survey of all inhabitants of Leiden, the Netherlands, over 85 years (n = 1258). In this paper we report on 532 subjects without neurological or psychiatric disease. Results show that the median score and lowest quartile cut-off score remain high until the tenth decade (median score = 28, lowest quartile cut-off score = 26). Thus age, in itself, is not a major limitation in using the MMSE. In this study a comparatively low level of education (the majority had 6 to 7 years of education) did not affect the results on the MMSE in a negative way, nor did we find an association with the use of psychoactive drugs. PMID- 2229863 TI - Assessing treatment decision-making capacity in elderly nursing home residents. AB - Clinicians usually employ indirect measures of cognitive and physical function in order to assess medical decision-making capacity. We tested a reference group of well elderly (Mini-Mental State Exam [MMSE] score = 29.1 +/- 0.8, mean +/- SD), for their understanding of three increasingly complex, hypothetical treatment situations or "vignettes"--use of a hypnotic, need for thoracocentesis, and desire for CPR. From this, we have developed a more direct, Guttman-like assessment of decision-making capacity. Of 51 Veterans Affairs nursing home residents (MMSE score = 22.4 +/- 6.9), only 33.3% demonstrated intact decision making capacity by this method, whereas 77% were felt by their primary physicians to be capable of giving consent for oral surgery; 37.3% had very impaired decision-making capacity; and 29.4% were intermediate in this ability. Judged against our more direct assessment of decision-making capacity, primary physicians' judgment of capacity for consent was 31% to 39% sensitive in identifying impaired decision-making and the MMSE was 53% to 63% sensitive. These measures were 100% and 82% to 83% specific in identifying intact decision-making capacity, respectively. We conclude that (1) more directly assessed decision making capacity varies noticeably among elderly nursing home residents and correlates in only limited fashion with frequently used cognitive screening methods; and (2) cognitive screening tests underestimate the prevalence of impaired decision-making capacity in this population. For informed consent and advance directives, our study suggests that decision-making capacity should be directly, rather than indirectly, assessed. PMID- 2229864 TI - An objective measure of physical function of elderly outpatients. The Physical Performance Test. AB - Direct observation of physical function has the advantage of providing an objective, quantifiable measure of functional capabilities. We have developed the Physical Performance Test (PPT), which assesses multiple domains of physical function using observed performance of tasks that simulate activities of daily living of various degrees of difficulty. Two versions are presented: a nine-item scale that includes writing a sentence, simulated eating, turning 360 degrees, putting on and removing a jacket, lifting a book and putting it on a shelf, picking up a penny from the floor, a 50-foot walk test, and climbing stairs (scored as two items); and a seven-item scale that does not include stairs. The PPT can be completed in less than 10 minutes and requires only a few simple props. We then tested the validity of PPT using 183 subjects (mean age, 79 years) in six settings including four clinical practices (one of Parkinson's disease patients), a board-and-care home, and a senior citizens' apartment. The PPT was reliable (Cronbach's alpha = 0.87 and 0.79, interrater reliability = 0.99 and 0.93 for the nine-item and seven-item tests, respectively) and demonstrated concurrent validity with self-reported measures of physical function. Scores on the PPT for both scales were highly correlated (.50 to .80) with modified Rosow Breslau, Instrumental and Basic Activities of Daily Living scales, and Tinetti gait score. Scores on the PPT were more moderately correlated with self-reported health status, cognitive status, and mental health (.24 to .47), and negatively with age (-.24 and -.18). Thus, the PPT also demonstrated construct validity. The PPT is a promising objective measurement of physical function, but its clinical and research value for screening, monitoring, and prediction will have to be determined. PMID- 2229865 TI - Hierarchical measures of physical function in ambulatory geriatrics. AB - Brief and uncomplicated methods for obtaining information on functional status would facilitate the assessment of older patients. We evaluated the potential usefulness, reliability, and validity of four hierarchical measures of physical function in 123 elderly subjects seen in four ambulatory geriatrics settings. Although the vast majority (83.2%) of subjects were fully independent on the Katz Activities of Daily Living Scale, a broader scope of functional difficulty was reported on the Spector-Katz, five-item OARS, and Rosow-Breslau scales. The three scales all had either borderline or more acceptable coefficients of scalability (0.57-0.77); the hierarchical order of items was not observed in 5.3% to 13.6% of subjects. Combining items from these established measures resulted in two new scales with acceptable scalability and construct validity; however, some errors in item order persisted. Although their ease of administration is clearly advantageous, clinicians using short hierarchical scales to assess functional status of older patients should be aware of their limitations. PMID- 2229866 TI - Timed manual performance in a community elderly population. AB - The extent of functional disability measured by performance of a series of simple manual tasks was determined in 1,286 elderly people, aged 66 to 98, who resided in central North Carolina. Missing data left 1,106 subjects for analysis. Poor manual performance was defined by either of two criteria: (1) inability to complete all the test items, or (2) taking longer than 350 seconds to complete the test. Using the first criterion, 113 persons (10.2%) were poor performers. When the two writing items were omitted from the analysis, 28 persons (2.4%) were in the poor performance group. Of the 993 persons who completed all items, 59 persons (5.9%) performed poorly. Using both criteria, the extent of functional disability was 16.1%; excluding the writing items, the extent of poor performance was 8.3%. Compared to those who performed well, those who performed poorly were older, poorer, less educated, more likely to be black, and less healthy. Because manual ability correlates highly with functional dependency and identifies those at risk for increased care needs, the magnitude of manual dysfunction noted in this survey has important implications for care providers and policy-makers. PMID- 2229867 TI - The age-associated decline in glomerular filtration in healthy normotensive volunteers. Lack of relationship to cardiovascular performance. AB - Whether the well-documented age-associated decline in the glomerular filtration rate, manifest as a decline in creatinine clearance, is secondary to an age related change in cardiovascular performance is at present unknown. To answer this question, we measured arterial blood pressure, 24-hour creatinine clearance, and cardiac output determined from gated cardiac blood pool scans in the sitting position in healthy normotensive men (n = 75) and women (n = 42) (ages 25 to 82 years), from the Baltimore Longitudinal Study on Aging. These subjects were selected for the absence of cardiovascular disease, renal disease, and confounding medications. By linear regression analysis, creatinine clearance, expressed in mL/min/m2, declined cross-sectionally with age (creatinine clearance = 90 -0.33[age], r = .31, P less than .001), whereas systolic blood pressure in mm Hg increased with age (systolic blood pressure = 111 + 0.27[age], r = .30, P less than .001); cardiac output in L/min/m2 did not vary with age (r = .03, P = .74). In stepwise multiple regression analysis with age, cardiac index, and systolic blood pressure as independent variables and creatinine clearance as the dependent variable, only age was a significant predictor of creatinine clearance. (F = 11.31, DF + 116, r = .30, P less than .001). Thus, the age-associated decline in creatinine clearance is not modulated by changes in cardiac index or systolic blood pressure in healthy normotensive subjects. PMID- 2229868 TI - Foci of increased T2 signal intensity in MR images of healthy elderly subjects. A follow-up study. AB - An 18-month follow-up study was conducted on 26 healthy elderly subjects with and without foci of increased T2 signal intensity on MR imaging. The subjects did not differ with respect to health status or cognitive performance as measured by the Cognitive Subscale of the Cambridge Mental Disorders of the Elderly Examination and the Mini Mental State Examination at follow-up. There was a significant decline in performance on the Digit Symbol Substitution Test in subjects who had evidence of T2 foci compared to the performance of subjects without T2 foci. This may indicate that the presence of T2 foci is correlated with subtle difficulties in learning and memory. PMID- 2229869 TI - Characteristics of an elderly driving population referred to a geriatric assessment center. AB - A retrospective, case-control study was performed to determine the characteristics of elderly drivers referred to an outpatient geriatric assessment center. It was hypothesized that the driving population was operating at a higher cognitive and functional level than nondrivers. One hundred eighty-two subjects meeting the entry criteria were studied. Twenty-three percent of the subjects were driving at the time of their assessment. Compared to nondrivers, drivers were younger (P = .0001), were more likely to be male (P = .003), scored higher on a mental status examination (P = .0001), and were more independent in Physical and Instrumental Activities of Daily Living (P less than .0001). Despite these findings, the mean Folstein Mini-Mental score for drivers (23.7) was below normal; 40% of drivers were diagnosed as having Alzheimer's dementia at the time of their evaluation, and over 26% of the drivers needed help with either dressing or bathing. The frequency of impaired elderly drivers in this referral setting was high. The authors conclude that conditions that affect the driving task are common in geriatric assessment centers. Prospective studies of elderly drivers are needed to answer the difficult question of who among the elderly should drive. PMID- 2229870 TI - Osteoporosis. New insights from bone densitometry. PMID- 2229871 TI - Osteoporosis made easy. PMID- 2229872 TI - An additional letter on CPR in nursing homes. PMID- 2229873 TI - Another swing of the pendulum. PMID- 2229874 TI - Postoperative erythropoietin levels. PMID- 2229875 TI - Foundations of psychoanalysis reconsidered. AB - Grunbaum's approach to psychoanalysis suffers from several difficulties. It imposes a standard of logical reductionism and methodological purity that not only violates the nature of psychoanalytic knowledge, but imposes an invalid standard of verification and scientific confirmation. It utilizes a brand of dichotomous reasoning that forces psychoanalytic propositions into artificial positions that do not reflect the actuality of analytic practice. It imposes a standard of verification that is impossible for psychoanalysis, along with all forms of psychological knowledge, to reach. It visualizes psychoanalysis as encompassing only one form of knowledge of human psychic life, forcing it into a model that eliminates other aspects of the psychoanalytic process, so that psychoanalysis is subjected to criticism only on one dimension among several--a kind of psychoanalytic straw man. The psychoanalysis that is so impaled often is difficult for the psychoanalytic practitioner to recognize. To the extent that Grunbaum's skillful and highly informed criticism of the philosophical bases of psychoanalysis encounters these difficulties, the value of his argument falls short of providing a useful basis for advancing psychoanalytic knowledge and particularly for promoting the quest for pertinent standards of validation within psychoanalysis. PMID- 2229876 TI - "Meaning" connections and causal connections in the human sciences: the poverty of hermeneutic philosophy. AB - In much of psychoanalytic theory and therapy, Freud repeatedly inferred a causal connection between thematically kindred events by relying on the kinship between their thematic contents. This paper strongly endorses his search for causal explanations. But it argues in detail that (1) his causal inferences from thematic connections rest on an important fallacy, which undermines major etiologic conclusions in psychoanalysis; (2) a related, weighty inferential error is damaging to the Freudian theory of transference, when it infers the pathogenic role of an early childhood scenario from the thematic reenactment (recapitulation) of that scenario in the adult patient's interactions with the analyst, and with other people. Both arguments draw on subject matter in psychoanalysis, physics, evolutionary biology, common-sense psychology, history, and medicine to arrive at a fundamental caveat for all of the sciences: Even when the thematic kinship (or so-called "meaning connection") between events is indeed of very high degree, this fact itself does not license the inference of a causal linkage between these events. A corollary of this result is that we must reject the accusation of Karl Jaspers and the hermeneutic philosophers that Freud's own conception of the psychoanalytic enterprise suffered from a "scientistic self misunderstanding." PMID- 2229877 TI - The rhetorical voice of psychoanalysis. AB - The rhetorical voice of psychoanalysis has a long history and has only recently come to be seen as a special feature of the theory. Its beginnings can be found in Freud's earliest pleadings for the usefulness of metaphor and analogy, although he felt that they were largely provisional and would eventually be replaced by more durable concepts. We have begun to see problems in replacing the central metaphors; the rhetorical base of psychoanalysis may be more enduring than we thought. While our metaphors may never provide epistemic access to the stuff of the mind, they can and do point to specific clinical encounters. Ways must be found to expand our rhetorical treasure chest and develop language even better suited to our concepts and observations. PMID- 2229878 TI - Helping patients by analyzing self-criticism. AB - This paper is addressed to patients' need for help with punitive self-critical attitudes. Such help has not always been sufficiently provided by psychoanalysts, owing to an unrecognized failure of neutrality. Historically, a gradual overemphasis on the concept of an unconscious sense of guilt has acted as a barrier to the appreciation of shame. An alternative concept, punitive unconscious self-criticism, which stands in contrast to constructive self criticism and is common to the painful affects of guilt, shame, humiliation, and depression, can facilitate helpful analytic treatment. Heinz Kohut's contributions are examined. His analytic stance is differentiated from his theories of development. In the former, characterized by an affirmative attitude, he takes a position of functional neutrality toward shame and pays consistent though unstated attention to the effects of punitive unconscious self-criticism. The affirmative attitude can be employed without adoption of Kohut's self psychology, i.e., without abandoning the basic psychoanalytic approach to mental conflict and development. The concept of punitive unconscious self-criticism and the concept of divergent conflict, provide sufficient explanatory power. Clinical examples are used to illustrate these ideas. PMID- 2229880 TI - Followup of psychoanalysis five to ten years after termination: III. The relation between the resolution of the transference and the patient-analyst match. AB - As part of a long-term followup study of the outcome of psychoanalysis, we examined the relation between the extent of resolution of the transference at termination and the characteristics of the patient-analyst match. For twelve of the seventeen patients interviewed five to ten years after termination of psychoanalysis, the researchers found that the patient-analyst match played a role in the outcome of the analysis. Illustrations of the influence of the match in cases where the transference was resolved and those where it was not are presented. PMID- 2229879 TI - Followup of psychoanalysis five to ten years after termination: II. Development of the self-analytic function. AB - Thirteen of seventeen patients in followup interviews five to ten years after the termination of analysis reported the development or refinement of a self-analytic capacity. According to the accounts of these patients, there did not appear to be a direct relation between the attainment of a self-analytic function and the extent of resolution of the transference neurosis or the maintenance of therapeutic gains after treatment. PMID- 2229881 TI - Neutrality in the analysis of action-prone adolescents. AB - An adolescent patient's action during analysis reflects both neurotic conflicts and the developmentally determined task of establishing an integrated self representation. Concern for the consequences of the action often provokes the analyst to respond, covertly, with interventions intended to change the action through influence rather than understanding. This can lead to a distortion of the analytic process which, in itself, may be an enactment of the developmental conflict. Examination of such interventions reveals a lack of analytic neutrality and an unconscious participation in the patient's neurotic and developmental conflicts. Clinical material from the analyses of two fourteen-year-old girls and a sixteen-year-old boy is presented to illustrate and support this hypothesis. PMID- 2229882 TI - An exploratory study of mother-child interaction during the second year of life. AB - The aim of this study was to further understanding of development during the crucial second year of life. The study employed a naturalistic, semistructured situation for the observation of mother-child behavior. The experimental stimulus was the progressive diversion of the mother's attention away from her child. This diversion evoked separation anxiety in the child and the individual and interactive regulatory behaviors of the mother-child pair. Concurrently, the child's behavior was observed in a play group situation. One set of rating scales was devised for assessment of the mother-child interaction, and another set for assessment of the child's functioning in the play group. The major hypothesis was that maternal and child behaviors that foster the child's successful handling of phase-specific stresses and developmental tasks will be positively correlated with the child's functioning in the play group. This hypothesis is supported by the findings of the study. PMID- 2229884 TI - On the girl's psychosexual development: reconsiderations suggested from direct observation. AB - Following on two decades of longitudinal direct observation of young children, revisions of two component parts of psychosexual theory seem warranted. First, direct observation does not support the concept of a "phallic" phase as being representative of the girl's first genital phase. Observational findings challenge "phallic" concept-dependent hypotheses Freud proposed in 1925, including how the girl enters her Oedipus complex as well as the nature of her wish to have a baby. In the children observed by the author, phallic aggression was not manifest as much in girls as in boys, between the ages of two and four. Second, it is proposed we put aside the "phallic" phase concept in our considerations of the girl's dynamics and that we heighten our awareness of her early experiences of ambivalence--which lie at the heart of the oedipal conflict- and which leads to a formulation of superego development in the girl more compatible with clinical findings. PMID- 2229883 TI - Does a panel discussion on analytic technique have any effect on an audience of analysts? AB - This is a report of a followup study to determine whether attending a panel discussion group on post-termination patient-analyst contact influenced the analytic audience's attitude on that subject. A questionnaire about post termination contact was given to 21 analysts who did not attend the discussion group and to 45 analysts before they attended. The same questionnaire was given again to both groups six months later. Responses by the 21 analysts who had not been present remained essentially unchanged. Responses of the 45 analysts, after attending the discussion group, when compared to responses of an earlier group of 300 analysts, showed an increase in the proportion of analysts who said, in reference to psychoanalytic psychotherapy patients, either that they hoped to hear from the patient or that they would like the patient to return to see them at some specified period after treatment termination. Attendance at the discussion seems responsible for a significant effect on the analytic audience's attitude on post-termination patient-analyst contact. PMID- 2229885 TI - The nature of the therapeutic action of psychoanalysis: how analysis works. Panel report. PMID- 2229886 TI - Sadism and masochism in neurosis and symptom formation. Panel report. PMID- 2229887 TI - Sympathoadrenal preganglionic neurons in the adult rabbit send their dendrites into the contralateral hemicord. AB - Sympathetic preganglionic neurons projecting to the adrenal medulla of the adult rabbit were retrogradely labelled with horseradish peroxidase. Preganglionic neurons were located in thoracic spinal cord segments T3-T12, peaking in number at T8, and only ipsilateral to the side of injections. However, retrogradely labelled dendritic processes of preganglionic neurons in the intercalated nucleus pars paraependimalys, the intercalated nucleus, and possibly even in the intermediolateral cell column, were observed in the contralateral hemicord. This suggests that the activity of sympathoadrenal preganglionic neurons could be modulated by both ipsilaterally and contralaterally descending pathways. PMID- 2229888 TI - Colonic transit time and anorectal manometric anomalies in 19 patients with complete transection of the spinal cord. AB - In order to determine the relative importance of sympathetic and parasympathetic centers in the control of colorectal motility, colonic transit and anorectal motility were studied in 19 patients with complete spinal cord transection: group 1 (n = 5) where transection was above T9; group 2 (n = 6) where transection was between T9 and L2; group 3 (n = 8) where transection involved S2-S4. Colonic transit time was calculated by the radiopaque markers. Methods and results were compared with those of eight controls, all bedridden for non-digestive surgery. Anorectal motility was investigated by anorectal manometry, and results were compared with those of 17 healthy controls. Both mean right and left colonic transit times were not different in the three groups of patients and the bedridden control group. Mean rectosigmoid and total transit time increased in groups 2 and 3. In five patients of group 3 the mean anal canal (lower part) pressure was higher than in controls. Recto-anal inhibitory reflex was present in all patients, but their was no correlation in group 3 between the volume of rectal distension and both amplitude and duration of the recto-anal inhibitory reflex, and in group 1 between rectal distension and the duration of the recto anal inhibitory reflex. Rectosigmoid transit time increased when sympathetic and parasympathetic spinal centers are injured, suggesting the importance of this extrinsic nervous control; right and left colonic transit are not affected by spinal cord lesion suggesting that the distal colon but not the proximal colon, is under spinal cord nervous control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229889 TI - The innervation of tracheal smooth muscle in the ferret. AB - The innervation of tracheal smooth muscle in the ferret has been studied by monitoring pressure changes in a fluid-filled segment of trachea in pentobarbitone anaesthetized animals. Stimulation of the peripheral cut end of the vago-sympathetic trunk elicited increases in trachea segment pressure only when activity was evoked in non-myelinated efferent axons, myelinated axons were without effect. Such excitatory responses were blocked by atropine. After atropine and elevation of trachealis muscle tone with 5-hydroxytryptamine, stimulation of the vago-sympathetic trunk produced a fall in tracheal segment pressure. These inhibitory responses were completely blocked by bretylium tosylate in six animals and markedly reduced in a seventh. It is concluded that contraction of tracheal smooth muscle in the ferret is cholinergically mediated and solely dependent on activity in non-myelinated vagal efferent axons and that inhibition is mediated by noradrenaline released from sympathetic nerve endings. A non-adrenergic inhibitory system would not appear to be present in the ferret. PMID- 2229890 TI - Interaction between cholinergic and adrenergic pathways of the hypothalamic ventromedial nucleus on cardiovascular regulation. AB - In this work we studied the possible interaction between cholinergic (muscarinic and nicotinic) and adrenergic (alpha 1- and beta-adrenergic) pathways of the hypothalamic ventromedial nucleus on the regulation of arterial pressure and heart rate in conscious normotensive rats. Mean arterial pressure and heart rate were recorded in rats with cerebral chronic stainless steel cannulae implanted directly into the ventromedial nucleus. The changes in arterial pressure and heart rate produced by the injection of the cholinergic agonist (carbachol or nicotine) into the ventromedial nucleus were studied before and after the injection of prazosin (an alpha 1-adrenergic antagonist) or propranolol (a beta adrenergic antagonist) into this same area. The injection of carbachol (2 nmol) or nicotine (40 mmol) into the ventromedial nucleus induced pressor and tachycardia responses. Previous treatment with prazosin or propranolol blocked the pressor response to carbachol and nicotine. Propranolol also abolished the tachycardic response to carbachol or nicotine, but prazosin reduced only the tachycardia produced by carbachol into the ventromedial nucleus. These results show an interaction between cholinergic and adrenergic pathways of the ventromedial nucleus affecting cardiovascular regulation and suggest that the alpha 1- and beta-adrenoceptors of this nucleus are involved in these responses. PMID- 2229891 TI - Effect of urethane anesthesia on the micturition reflex in capsaicin-treated rats. AB - Cystometry was performed on rats with a chronically implanted intravesical catheter (2 days before cystometry) before and after induction of urethane anesthesia. Four groups of animals were investigated: group A, vehicle-treated; group B, capsaicin-treated as adults (50 mg/kg s.c.) 4 days before cystometry; group C, capsaicin-treated as adults (125 mg/kg s.c.) 4 days before cystometry; and group D, capsaicin-treated as newborns (50 mg/kg) 2 months before. Rats of group D had a markedly enlarged bladder. Before induction of urethane anesthesia, the bladder capacity of rats of groups A, B and C was not significantly different from each other, while that of rats of group D was larger than controls. After induction of anesthesia bladder capacity in groups B and C was significantly increased as compared to group A and micturition was abolished in group D (overflow incontinence). Amplitude of micturition contraction was significantly reduced in all groups after induction of anesthesia but was unaffected by capsaicin pretreatment. It is concluded that the facilitatory action of capsaicin sensitive nerves on micturition threshold is more evident in anesthetized than awake rats and that capsaicin-resistant bladder afferents are more sensitive to the depressant action of urethane than the capsaicin-sensitive ones. PMID- 2229892 TI - Controlled bradycardia induced by nasal stimulation in the muskrat, Ondatra zibethicus. AB - Respiration was disrupted and bradycardia induced in anesthetized muskrats by stimulating the nasal cavity with a stream of either water or various concentrations of ammonia vapors. When responses induced by either ammonia or water were compared, ammonia vapors were considered preferable because the responses could be maintained reliably through relatively rapid periods of stimulation, and the post-stimulus recovery of heart rate and respiration was more predictable. Moreover, the bradycardia induced in the first 5 s of stimulation by dilutions of ammonia vapors was graded. After injections of lidocaine were made into the nucleus tractus solitarius a profound bradycardia to ammonia stimulation persisted despite disruption of normal respiratory rhythms and an inhibition of the baroreceptor reflex induced by phenylephrine administration. These results show that ammonia vapors stimulating the nasal chambers effectively elicit cardio-respiratory adjustments in anesthetized muskrats and that the bradycardia may be controlled by varying the intensity of the peripheral stimulus. The trigeminal contribution for this is emphasized since the bradycardia persists after reversible blockade of the solitary complex. These data suggest that the trigeminal input to cardiac motorneurons is via relatively few synapses and is over circuits which run parallel to those modulating cardiac activity in response to chemoreceptors, baroreceptors and pulmonary afferent fibers. PMID- 2229893 TI - Effects of calcitonin gene-related peptide and vasoactive intestinal peptide on nicotine-induced sweating in man. AB - The effects of two neuropeptides, calcitonin gene-related peptide and vasoactive intestinal peptide on nicotine-induced sweating in human skin were investigated. Intradermal injection of nicotine induced local sweating and each peptide, administered together with nicotine, inhibited these responses in a concentration dependent manner. The concentration of calcitonin gene-related peptide for threshold and half-maximum inhibition were about 10(-10) M and 10(-8) M, respectively, while those of vasoactive intestinal peptide were approximately 10( 9) M and 10(-7) M, respectively. The results suggest that calcitonin gene-related peptide and vasoactive intestinal peptide have inhibitory effects on the nicotinic action, and release of endogenous calcitonin gene-related peptide and/or vasoactive intestinal peptide may influence sweating in human skin under physiological conditions in vivo. PMID- 2229894 TI - [Scintigraphy of the lacrimal ducts: the value of the lateral view in the postoperative period]. AB - Lacrimal scintillography, a simple, non traumatic, and physiological method, has been for a long time an useful exploration in the study of lacrimal excretory pathology. It allows an accurate diagnosis especially in the case of functional stenosis and, due to its ability to indicate the exact seat of obstruction, this technique is able to determine the surgical treatment required. This study underlines the contribution of lacrimal scintillography in the control of surgical anastomosis permeability, because of a modification in the initial technique: the use of scintillography in employing the lateral view rather than the front view, usually used, permits a better visualisation of the new surgically created excretory passage, particularly in the posterior area of nasal fossae. PMID- 2229895 TI - [Epikeratoplasty without sutures using collagen IV lens in monkeys: description of the surgical technic]. AB - The authors describe their original epikeratoplasty technic without sutures which is compatible with the use of collagen IV lens. They describe the first four observations of primates operated on using this technic. At first the epithelium is removed at the cornea center and a trepanation is made of 4 mm diameter and 0.1 mm depth. The bottom of the trepanation is then cut horizontally, and the periphery of the lens is put in the cornea stroma. Later the epithelium will recover the collagen lens. The lens is perfectly set in the cornea. We don't use any suture and so we avoid astigmatism and neovascularisation. The follow-up consisted of biomicroscopic examination photography, specular microscopy, pachymetry, photokeratoscopy (Nidek System) tonometry and histology. Clinical observance showed a perfect lens tolerance. The cornea is immediately transparent and within a week epithelial cells recovered the lens of three animals out of four. The photokeratoscopy study proved the important cornea refraction modification. This technic is reversible and the lens can be exchanged. A study of histology has begun and already shows a pluristratified epithelium. Further studies will test the biomaterial stability and ultra structural relations between the collagen IV lens and epithelial cells. PMID- 2229896 TI - [Keratoplasty in children. Analysis of 127 surgically treated eyes over 10 years]. AB - One hundred and twenty-seven eyes of children less than 15 years of age underwent keratoplasty with one to ten years follow-up. The cases were divided into three groups of age, and the results are compared. Graft transparency has a direct correlation with the age of patient and type of corneal disease. Penetrating keratoplasty carries a better surgical and visual prognosis when carried out late in childhood. This is not only the fact of the particular etiologies found in this subgroup of age. When adjusting the results to the both factors age and etiology, we have demonstrated their independent. The visual benefits of corneal transplantation in selected cases in children appear to outweigh the difficulties and problems engendred by this procedure. PMID- 2229897 TI - [Treatment of dry eye by temporary punctum plug. Comparison with a control group]. AB - 35 patients with chronic dry eye were treated with punctum plug on one side only. The other side was a control: after simulation dilatation, the patient underwent a simulation insertion. This is an open study in which only the patient ignored the reality of treatment. The study was prospective. 28 females and 7 males were enrolled in this study. The age' average was 53. The follow-up average is 5.3 months. The etiologies were: idiopathic dry eye: 10 cases, Sjogren's syndrome: 11 cases, drug induced dry eye: 6 cases, filamentous keratitis: 4 cases. Other: 4 cases. Enrollment criteria were: functional symptomatology not answering to topical therapy (physiological serum drops) associated with one or more of the following items: positive Rose Bengal staining and/or Schirmer lower than 5 mm in 5 min and/or filamentary keratitis. Subjective improvement is significantly better after closing the two puncta on the same side (77%) than the other side (placebo) (17%) (p less than 0.001). This difference is also demonstrated for the improvement of Rose Bengal staining (p = 0.068) and for Schirmer's test (p = 0.002). These results demonstrated the effectiveness of this therapy versus placebo. Results after closing the 2 puncta on the same side are better than after closing one punctum. PMID- 2229898 TI - [Complications of punctum plug in the symptomatic treatment of dry eye]. AB - 76 patients with dry eyes were treated by mechanical obstruction of lacrymal puncta. The sex ratio is: 62 females and 14 males. The age average was 55, ranging from 12 to 88. The etiologies were: Sjogren's syndrome: 16 cases (21%); filamentous kerato-conjonctivitis sicca: 12 cases (15%); anxiolytical and anti depressant treatments: 10 cases (13%); complicated viral kerato-conjonctivitis: 4 cases (5%); post radiotherapy dry syndrome: 3 cases (4%); idiopathic and various etiologies: 31 cases (40%). The 149 plugs are completely made of hydrophobic silicone; 20 had a barb inclined on the neck axis. Insertion was achieved after tropical anesthesia in 90% of the cases. 121 plugs (81%) did not lead to any anatomical complication (the average duration remaining on time interval of implantation per plug was of 5 months). Functional tolerance depends on the quality of plug-punctum adjustment. Plug protrusion is the main cause of intolerance and disappearance. The complications were: rupture of punctum during dilation: 1%; suppurative canaliculitis: 1.3%; disappearance: 16%; epiphora: 22%. No intra-canalicular migration was observed. We check canalicular permeability in 26 cases, after loss or removal: che was normal 23 times (average time-interval: 5 months). We had 3 cases of canalicular stenosis after 4 months, 5 months and 18 months of intubation. PMID- 2229899 TI - [Treatment of superficial herpes simplex keratitis with vidarabine (Vira A): multicenter study of 100 cases]. AB - The efficacy of 3% Ara-A ophthalmic ointment (Vira A) has been evaluated on 100 epithelial herpetic keratitis; the poor intra-ocular penetration of Ara-A explains the exclusion of stromal keratitis and kerato-unveitis. Patients were treated 5 times a day until complete epithelial healing of ulcers, then twice a day during 7 days. Healing was obtained within 10.6 days for 87% of the patients, who have been treated by Ara-A at first (n = 77) or after failure of IDU or of IDC (n = 23). The healing rate was higher for the 52 first ocular episodes (92%) than for the 48 recurrences (81%); it decreases to 77% for recurrences after failure of IDU or IDC. Geographic ulcers heal in 76% of cases only. Their length has no influence on their healing. The longest healing time, 10.6 days, can be explained by the long period of time before beginning to apply Ara-A, 12.8 days: significative correlation between both periods of time is highlighted and shows the advantage of an early treatment. The need for a local corticotherapy (n = 8) does not hinder healing in 15.5 days. Two weeks after discontinuation of the treatment, 3 patients presented a relapse, sensitive to a 2nd Ara-A course; a maintenance treatment, superior to 7 days, is necessary. Tolerance to Vira A ointment is good. Indications of Ara-A during ocular herpes are superficial keratitis, especially those resistant to IDU or, from experimental data, to ACV, and their prevention by a possible long term treatment. PMID- 2229900 TI - [Malignant nasal oncocytoma disclosed by mucocele of the lacrimal sac with hemolacrimia]. PMID- 2229901 TI - [Epithelioma of the medial canthus. Retrospective study of 47 surgically treated cases]. AB - The authors report a retrospective study of 47 cases of carcinoma of the medial canthal area which were operated on between 1982 and 1987. Patient age and the histological frequency of basal cell carcinoma were similar to those of studies previously reported. Local extension must be evaluated at the initial clinical examination and computed tomography can be very useful. Frozen section for histopathologic study should be done if there is the least doubt. The surgical treatment and different methods of local reconstruction are discussed. PMID- 2229902 TI - [Idiopathic preretinal macular fibrosis. Study of correlation between morphologic changes and visual acuity]. AB - Idiopathic preretinal macular fibrosis is an affection characterized by the development of preretinal membranes, macular distortion and, sometimes, macular edema. These changes as well as the consequent reduction of the visual acuity may vary very widely from one case to another. In this study, the degree of correlation among the various retinal morphological changes and among them and the visual acuity was investigated. This study shows that the importance of retinal distortion is strictly dependent on the appearance of the preretinal membranes that the appearance of the preretinal membrane and the importance of the retinal distortion are equally valid predictors of visual acuity, that the macular edema (defined as fluorescein leakage) depends mainly on the degree of contraction of the preretinal membrane and that such leakage does not represent the best parameter in order to predict the visual acuity. PMID- 2229903 TI - Symptomatic bipartite sesamoids. AB - The great toe sesamoids have been well reported in the literature, in every aspect. Much has been written about the normal anatomic variation of partite metatarsophalangeal sesamoids. It is the purpose of this article to present a theory explaining the common occurrence of a symptomatic partite sesamoid. The authors believe there is a high rate of occurrence of symptomatic partite sesamoids, especially when associated with hallux abducto valgus. Presented is information concerning the internal and external structural components of a bipartite metatarsal sesamoidal joint, which may inherently lead it to symptomatology. PMID- 2229905 TI - Correlation between hallux valgus angle and age. AB - A study was made of the relationship between the hallux valgus angle and age. Between January 1983 and June 1985, 464 hallux valgus operations were performed on 404 patients at the Department of Orthopedic Surgery at Huddinge Hospital. The mean age of the patients was 54 +/- 12 years (range 16 to 75). The patients were divided into six groups with regard to nature and extent of radiographic changes. Linear regression analysis was used for analysis of the correlation between age and hallux valgus angle. A significant correlation was found in group 1: hallux valgus grade 1, type I (great toe rotated, slight bunion) and group 6: hallux valgus grade 2, type III (great toe rotated, severe bunion and severe arthrosis). There was a large scatter around the lines, however, which means that age is poor predictor of the hallux valgus angle. PMID- 2229904 TI - In-situ chondrosarcoma of the foot arising in a solitary enchondroma. AB - Chondrosarcoma of the foot is very rare. Secondary malignant transformation of a solitary enchondroma of the foot occurring in a 66-year-old man is reported. A rapid increase in size of a previously known enchondroma and pain may suggest a malignant transformation. Surgical resection is the choice of therapy. PMID- 2229906 TI - Osteochondromatosis of the ankle. AB - Synovial chondromatosis is a rare condition that presents as juxta-articular masses which arise due to metaplasia of the synovia and formation of cartilaginous nodules. It will present as a monoarticular mass that is a chronically progressive condition without any tendency to resolve spontaneously. The authors present a review of the literature with a rare case study involving the ankle joint of a 29-year-old black male. The clinical presentation, surgical excision, histologic analysis, and postoperative course are discussed. PMID- 2229907 TI - Effects of ankle arthrodesis on the subtalar and midtarsal joints. AB - Proper positioning of an ankle arthrodesis is crucial, since it will allow compensatory motion to occur in the rearfoot complex. Arthrosis in the rearfoot can be expected several years after fusion; however, malalignment can potentiate rearfoot arthrosis and lead to a painful and nonfunctional gait. PMID- 2229908 TI - Scanning and light microscopic study of irrigated and nonirrigated joints following burr surgery performed through a small incision. AB - Research was conducted on young, adult male rabbits where osseous burr surgery was performed through a small incision using two methods of joint debris extrusion. Surgical joint debris was found in all specimens at 1 week following surgery. Also, 1 week postoperatively, the surgically untouched chondral and subchondral joint aspects were intact in both irrigated and nonirrigated specimens. There was, however, subchondral bone inflammation in all specimens but the nonirrigated population had a greater inflammatory subchondral infiltrate. The synovium was more inflamed in the nonirrigated group. Bone particles, observed with scanning electron microscopy, generally appeared to be only slightly more evident in the nonirrigated group. Metal particles were observed in several specimens. By 28 weeks, joint debris was practically undetectable. In the irrigated specimens the chondral and subchondral portions presented with occasional degenerative focal loss of the chondral and subchondral layers. In comparison, the nonirrigated group demonstrated not only occasional but moderate to-frequent focal loss with fissuring in the chondral and subchondral layers in addition to extrinsic repair of the cartilage surface. Subchondral bone inflammation was also more severe in the nonirrigated group. Observations from this project confirm that joint debris is removed through intrinsic joint processes and further suggests that the postoperative course of inflammation is not a totally abrasion-related phenomenon. The findings support the use of intraoperative irrigation as opposed to debris extrusion without irrigation in order to reduce both immediate and chronic postsurgical inflammation. PMID- 2229909 TI - Stenosing tenosynovitis of the flexor hallucis longus at the ankle joint. AB - The discussion of stenosing tenosynovitis of the flexor hallucis longus at the level of the ankle joint is not found in the literature with frequency. A thorough understanding of the involved anatomy is necessary when considering this condition. A strong clinical suspicion, coupled with appropriate diagnostic tests, is necessary to arrive at a proper diagnosis. Various treatment options may be considered. However, surgical decompression of the stenosed sheath ultimately is recommended by the authors. PMID- 2229910 TI - Cobb repair for tibialis posterior tendon rupture. AB - The tibialis posterior is the main dynamic stabilizer of the hindfoot against a valgus deformity. Its rupture results in hindfoot valgus with a considerable biomechanical disturbance and functional loss in the affected foot. A new method of reconstruction of this tendon is described which involves the use of half the tendon of tibialis anterior. PMID- 2229911 TI - Melorheostosis: a case report and literature review. AB - Melorheostosis is a rare form of cortical hyperostosis that resembles wax dripping down the side of a candle. This disease usually affects the long and short bones of an extremity. Literature review and a case report will be discussed with respect to incidence, clinical presentation, radiographic appearance, and treatment. PMID- 2229913 TI - Classification of tendo Achillis rupture with consideration of surgical repair techniques. AB - The author presents a classification system for complete tendo Achillis rupture. The system is based upon experience following 28 repairs and 102 lengthenings and gastrocnemius recessions. Specific surgical procedures based on this system are reviewed. PMID- 2229912 TI - Osteoblastoma of the distal phalanx of the hallux. AB - Osteoblastoma is a very rare bone tumor infrequently reported in the podiatric literature. The authors present a review of this tumor and the types of modalities that may be used to detect and diagnose these tumors. They also present a surgical approach to the resection of these bone tumors. PMID- 2229915 TI - Squamous cell carcinoma: a pedal case presentation. AB - Squamous cell carcinoma of the foot is a relatively uncommon pedal neoplasm. The authors discuss the etiology, metastatic rate, incidence, morphology, treatment and the histology of this entity. Additionally, the authors present a clinical case report successfully treated by surgical extirpation. PMID- 2229914 TI - Arthrodesis of the first metatarsophalangeal joint: a review of the literature and long-term retrospective analysis. AB - A retrospective analysis of arthrodesis of the first metatarsophalangeal joint was done to determine the procedure's long-term subjective and objective results. The authors reviewed the long-term results of arthrodesis in 25 patients with 32 operated feet. The average age was 54.8 years (range 22 to 72 years), and the average length of follow-up was 31.9 months (range 12 to 84 months). The patients were questioned regarding pain, activity, cosmesis, and willingness to have the operation performed again. The subjective results were good or excellent in 26 feet (81% success rate). The primary postoperative complaints were pain in the interphalangeal joint (four feet), and a callosity or pain under the first metatarsal head (four feet). Radiographic examination revealed that the procedure provided a good reduction of the hallux valgus angle (preoperative average 33.7 degrees; postoperative average 17.4 degrees) and intermetatarsal angle (preoperative average 16.2 degrees; postoperative average 12.0 degrees). The authors believe that this procedure is a reliable, effective treatment whenever stability is required at the first metatarsophalangeal joint. PMID- 2229917 TI - Closed reduction of a proximal interphalangeal joint dislocation. AB - A case report involving the closed reduction of a simple dislocation of a lesser digit is presented. The technique of reduction is illustrated and discussed. Classification of both simple and complex dislocations are reviewed. PMID- 2229916 TI - Septic bursitis of the foot: diagnosis, management and end-result. AB - Septic bursitis of the foot is a disorder infrequently reported in the medical literature. This infrequent reporting may represent a true low incidence of occurrence or may be a reflection of failure to recognize and diagnose this condition. This paper retrospectively reviews the presentation, clinical course, and outcome of patients presenting with septic bursitis of the foot. The authors have reviewed those features of this disorder that may aid the clinician in diagnosis and management of this infrequent, but disabling entity. They describe a brief case history of 10 patients with septic bursitis of the foot, provide radiographic and microbacterial evaluation, and give an outcome determination. They make recommendations for diagnosis and treatment based upon this review of patients and review of the literature. PMID- 2229918 TI - Tumoral calcinosis with extensive pedal involvement. AB - Tumoral calcinosis is characterized by excessive calcified masses in the soft tissues of young adult extremities. The histologic and radiologic appearances are discussed. A 56-year-old female pathologic case is reviewed. PMID- 2229919 TI - Diseases of the foot: test of radiographic interpretation. PMID- 2229920 TI - Polyclonal stimulation of lymphocytes induced by beta blockers in the mouse: influences of age, sex and strain. AB - The immune effects of acebutolol, a beta-blocker, are investigated in various strains of mice. In 6-12 weeks old C57Bl/6 female mice, an increase in the number of immunoglobulin secreting cells is observed only at the age of 9 weeks. At that age, such an effect is seen neither in C57Bl/6 male mice nor in female mice from 6 other strains including OF1 outbred mice. An increase in anti-trinitrophenol plaque forming cells is found in 9 week old C57Bl/6, Balb/c and CBA female mice. PMID- 2229921 TI - The effects of cytochalasins on lymphocytes: V. Interaction of trifluoperazine and cytochalasin B in inhibition of human lymphocyte proliferation. AB - Trifluoperazine (TFP), a phenothiazine derivative, is known to inhibit calmodulin mediated phenomena. We report here that TFP reversibly inhibited lymphocyte proliferative responses to mitogenic lectins. This inhibition was observed only when TFP was added during the early stages of exposure of lymphocytes to the stimulus. Furthermore, at suboptimally inhibitory concentrations of each compound, effects of TFP on lymphocyte proliferation were additive to those of cytochalasin B (CB). Incubation of lymphocytes in TFP (10(-5)-10(-4) M) markedly inhibited cytochalasin B binding to the actin associated, low affinity binding site without affecting its binding to the high affinity site or to the medium affinity site. This effect developed gradually during incubation with TFP, becoming demonstrable after 30 minutes reaching maximum after 30-60 min of incubation at 37 degrees. The findings suggest the occurrence of an interaction of TFP with the lymphocyte cytoskeleton, which may play a role in the impairment in the transmission of the mitogenic signal. PMID- 2229922 TI - Modulation of the interleukin 2 receptor by maternal and cord blood serum. AB - In this report, the potential inhibitive action, of maternal serum (retroplacental and peripheral), and cord blood serum on the expression of the Il2r has been studied. Calf and male serum were used as a control. In order to have an optimal Il2r expression, a previous PHA cellular stimulation was performed. The maternal serum's Il2r inhibitive property was measured during and after the pregnant period. The presence of Il2r on maternal lymphocytes, cord blood cells, and unrelated donor mononuclear cells has been investigated (after a PHA stimulation assay). The downregulated Il2r expression of neoplastic cell line (Hut78 cell line) under the influence of maternal serum has been observed. The examination of the inhibitive action due to maternal serum has suggested that a factor included in the IgG fraction is mainly responsible for the downregulating property concerning the Il2r expression. A possible mechanism for the action of this factor has been studied. Further experiments suggest that the addition of recombinant Il2 during the action of low doses of maternal IgG allows a partial reexpression of the Il2 receptor. However, at physiological concentrations of IgG, the Interleukin 2 receptor downregulation becomes irreversible. PMID- 2229923 TI - 3-Methylcholanthrene-induced immunosuppression in mice to Trichinella spiralis antigens. AB - The immunosuppressive effects of in vivo (subcutaneous) exposure to 40 or 80 mg/kg 3-methylcholanthrene (MC) were examined in aryl hydrocarbon hydroxylase (AHH) responsive C57BL/6 (B6) and AHH non-responsive DBA/2 (D2) inbred strains of mice. Twenty-four hours after treatment with carcinogen or vehicle alone, animals were primed with crude L1 muscle larvae antigen from T. spiralis. Immune status was assessed in vitro after six days as antigen-specific lymphoproliferation. The proliferation of splenocytes from MC-treated D2 and B6 mice was significantly impaired compared to controls. To examine the cellular basis of the immunosuppression, primed splenocytes from control and MC-treated mice were separated into adherent and non-adherent fractions on Sephadex G-10 columns. When antigen-pulsed adherent cells from MC-treated B6 and D2 mice were recombined with control non-adherent cells from syngeneic and B6D2F1 mice, T-cell proliferation was significantly reduced. This suppression was not observed with the addition of increased numbers of adherent cells. Non-adherent cells from MC-treated mice showed a decreased capacity to respond to the presence of control antigen-pulsed adherent cells from appropriate mice. These results suggest that MC treatment has a similar suppressive effect on the immune responses of both B6 and D2 mice that involves the quality of accessory cell-T-cell interactions. PMID- 2229924 TI - Panax ginseng as a potential immunomodulator: studies in mice. AB - There has been continuing interest in the development of synthetic and natural compounds which modify the immune response, particularly for the treatment of AIDS and cancer. Panax ginseng, employed for its putative medicinal properties in South Asia, was examined for its immunomodulatory properties in mice. A systematic evaluation of multiple immune system components revealed that Panax ginseng stimulated basal natural killer (NK) cell activity following subchronic exposure and helped stimulate recovery of NK function in cyclophosphamide immunosuppressed mice but did not further stimulate NK activity in poly I:C treated mice. Other immunological parameters examined, including T and B cell responses were not affected. Panax ginseng provided a degree of protection against infection with L. monocytes but did not inhibit the growth of transplanted syngeneic tumor cells. Increased resistance to L. monocytogenes was not detected in challenged mice previously given immunosuppressive doses of cyclophosphamide. Taken together, these data suggest that Panax ginseng has some immunomodulatory properties, primarily associated with NK cell activity. PMID- 2229925 TI - Oral administration of Chlorella vulgaris augments concomitant antitumor immunity. AB - Chlorella vulgaris, an unicellular green algae, or its acetone-extract (Ac-Ex) were administered orally to Meth A tumor bearing BALB/c or (BALB/c x DBA/2)F1 (CDF1) mice. When CDF1 mice were fed daily with 10% dried powder of Chlorella vulgaris (CVP) containing diet before and after Meth A tumor inoculation, the growth of rechallenged Meth A tumor was significantly suppressed in an antigen specific manner. Augmentation of antitumor resistance was exhibited also by Winn assay using lymph node cells of tumor-bearing mice orally administered with CVP or Ac-Ex. Antigen-specific concomitant immunity in these mice were mediated by cytostatic T cells but not by cytotoxic T cells. Natural killer cells seemed not to contribute in antitumor resistance in this system. PMID- 2229926 TI - Action of a mycotoxin (diacetoxyscirpenol) on the immune response of the mouse- interaction with an immunomodulator (OM-89). AB - The action of diacetoxyscirpenol (DAS)--a mycotoxin that belongs to the family of trichothecenes--on the immune system of the mouse was investigated. Two experimental models were used: 1) bacterial infection with Salmonella typhimurium and 2) the PFC (plaque-forming cells) test on the splenic lymphocytes of the mouse. The results obtained showed that these were dependent on the chronological order of the administration of DAS. When the toxin was administered after a bacterial infection or antigenic stimulation, it was observed an increase in the mortality rate and a very significant decrease in the antibody response. By contrast, when this mycotoxin was administered before the bacterial infection or antigenic stimulation, the results obtained were close to those from the controls. The importance of the administration of an immunomodulator of bacterial origin OM-89 before the immunodepression with DAS was shown. PMID- 2229927 TI - Epidemiology and clinical characteristics of endemic cretinism in Sicily. AB - In this study we report the prevalence of endemic cretinism in the general population of two iodine deficient areas in Northeastern Sicily that were described more than 10 yr ago. In addition, the individual characteristics of endemic cretins are considered in order to define the typical expressions of this major iodine deficiency disorder in Sicily. Forty-three mental defectives were identified: 22 were living in an area with three bordering and closely connected municipalities within the province of Messina and with a population of 17,485 inhabitants (prevalence = 0.13%). Three out of the 22 were school-age children. The other community, in the province of Catania, was constituted by a unique and mostly agricultural hamlet, and showed a prevalence of cretinism that was 0.68% (21/3,100). Among the 43 mental defectives, 16 (37%) presented prominent neuromotor and neurosensorial disorders, including deafmutism and were euthyroid, thus conforming to the neurological type of cretinism; 13 (30%) were hypothyroid and exhibited stunted growth without significant neuromotor and neurosensorial impairment (myxedematous cretins). In the remaining 14 individuals (33%) neurological disorders were associated with stunted growth and clinical or biochemical hypothyroidism. These data indicate that also in Sicily endemic cretinism is a continuum of a variety of forms: among these the pure neurological and pure myxedematous forms represent the two extremes. Our observations also indicate that endemic cretinism still represents a major public health problem in Sicily. The finding of 3 endemic cretins younger than 13 yr suggests the persistence of this disorder even in the presence of improved economic, social and nutritional conditions. PMID- 2229928 TI - Plasma C-peptide response to oral glucose load in hyperthyroidism. AB - Aim of the present study was to evaluate the pancreatic beta cell response to oral glucose load in a group of patients with hyperthyroidism. For this purpose plasma C-peptide at fasting and after a 100 g oral glucose load was measured in 8 newly-diagnosed untreated hyperthyroid patients with fasting normoglycemia, and 8 sex-, age-, and weight-matched healthy controls. As compared to healthy subjects, patients with hyperthyroidism showed higher plasma glucose levels (incremental area 5405 +/- 742 vs 2729 +/- 539 mg/dl x 180 min, p less than 0.05), and slightly reduced plasma C-peptide concentrations (incremental area 166 +/- 12 vs 182 +/- 36 pmol/ml x 180 min, p = NS) following oral glucose load. The ratios between plasma C-peptide and plasma glucose incremental areas were lower in hyperthyroid patients than in controls (3.66 +/- 0.85 vs 10.41 +/- 3.08, p less than 0.05). These data suggest that hyperthyroidism is characterized by a decreased pancreatic beta cell response to oral glucose load. PMID- 2229929 TI - Quantification of intracellular calcitonin gene transcripts in human medullary thyroid carcinoma (MTC) by in situ hybridization. AB - The human calcitonin gene generates 2 distinct mature mRNAs by alternative RNA processing, encoding calcitonin (CT) in thyroid C-cells or a neuropeptide (CGRP) in the brain. We evaluated quantitatively by in situ hybridization the expression of the CT gene in tissue section of 5 MTCs (2 sporadic and 3 familial forms). The primary tumor of one MTC was compared to a brain metastasis. In situ hybridization was carried out with tritiated cDNA probes coding for CT and CGRP mRNA. After autoradiography the number of silver grains was counted in 400 cells by computerized analysis of digitized images and expressed as the labelling level (L.L. = grain area/cell area per day of autoradiographic exposure). This was used to calculate the relative abundance per cell of the specific messengers studied, which depends on the autoradiographic efficiency and the specific activity of the probe used. The CT mRNA content was 3.25-6.55 10(-10) micrograms equivalents in the 3 familial forms of MTC and 4.95-9.25 10(-10) micrograms equivalents for the 2 sporadic forms. The levels of CT mRNA in the brain metastasis and in the primary tumor were identical (4.10 10(-10) micrograms equivalents). CGRP mRNA expression was weaker in the sporadic and in the familial thyroid tumors (0.60 1.65 10(-10) micrograms equivalents). The content of mRNA CGRP in the brain metastasis (0.60 10(-10) micrograms equivalents) was lower than that in the primary tumor (1.05 10(-10) micrograms equivalents).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229931 TI - Bone mineralization and calciotropic hormones in children with hyperthyroidism. Effects of methimazole therapy. AB - We studied bone mineralization and calcium homeostasis in two children with hyperthyroidism before and during 3 yr of methimazole therapy in order to evaluate the effects of thyrotoxicosis and its therapy on mineral metabolism. Case 1, female, 4.1 year old with hyperthyroidism from 6 months. Biochemical data: increased thyroid function, phosphate and osteocalcin, decreased 1,25(OH)2D levels. X-ray: severe osteoporosis; bone mineral content (BMC) -23.0%, BMC/BW 25.1%. Case 2, female, 7.4 year old with hyperthyroidism from 9 months. Biochemical data: thyroid function, ionized calcium and osteocalcin were increased, 1,25(OH)2D and intact PTH were decreased. X-ray: severe osteoporosis: BMC -32.8%, BMC/BW -36.0. After the patients were euthyroid, they showed an increase of 1,25(OH)2D and intact PTH into normal values and a fall in calcium and phosphate. Osteocalcin levels returned in normal range one yr after first evaluation. Bone mineral analysis showed no variation of BMC and BMC/BW in the first 6 months of therapy and an increase in the following 6 months. In the following two years BMC and BMC/BW rose to normal range. Our study provides further evidence that in hyperthyroidism an altered mineral homeostasis is present with a reversible disturbance in vitamin D metabolism. We found that the return to euthyroidism was associated with a normalization of mineral homeostasis and with a recovery of bone mineralization. Osteocalcin assay may be an useful index to monitor bone metabolism in hyperthyroidism. PMID- 2229930 TI - Chronobiology of catecholamine excretion in normal and diabetic men. AB - The adrenomedullary response to stimuli is often elevated in poorly controlled insulin dependent diabetic patients, and it is controversial whether the adrenomedullary hyperactivity induces the suppression of the circadian rhythm of catecholamines. We have studied the urinary excretion of catecholamines in 11 diabetic patients during 48 h in 4-h collections. Eleven age and weight matched normal subjects served as controls. A circadian rhythm was detected for adrenaline and noradrenaline excretion both in normal and diabetic subjects, with the highest value for both catecholamines in the early afternoon. The mean daily adrenaline levels were significantly higher in diabetic than in control subjects (p less than 0.05). The dopamine excretion was correlated with noradrenaline excretion in normal subjects but did not show a definite circadian rhythm. We conclude that the adrenomedullary hyperactivity does not affect the rhythmic fluctuations of adrenaline and noradrenaline. The dopamine excretion does not show circadian variations and this probably reflects the absence of a single controlling oscillator. PMID- 2229932 TI - The social outcome of adults with constitutional growth delay. AB - It is well established that children with extreme short stature, secondary to GH deficiency (GHD) or achondroplasia, face a disability that may affect their adult psychosocial outcome, while contrasting data are reported for short normal children. In our hands, adults with GHD have shown an unsatisfactory psychosocial adjustment due to the low adult height and hypothetically to the persistent GHD. This study has been carried out to evaluate the influence of growth in height on the social outcome in 45 adults with constitutional growth delay (CGD). Interviews with subjects and parents were used for assessment. Data obtained were compared with those found in an age, sex and social matched control group of adults with normal height. Some issues were also compared with the data we previously found in adults with GHD. Present mean age of the patients is 24 +/- 2 yr. A high percentage (32.8%) of unemployment or underemployment (part-time work) was found. Four patients (8.8%) were married, while 84.4% lived with their parents or relatives, confirming the notion of prolonged economic dependency on the family. The patients preferred single sporting activities, avoiding team work. Surprisingly, scholastic achievement was in general similar to that observed in controls. Similar findings have been previously observed in patients with GHD. Since no defect in GH secretion has been documented in CGD, the presence of a negative psychosocial outcome more probably seems to be due to the final unsatisfactory height rather than to a GH defect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229934 TI - Cytogenetic analysis in congenital hypothyroidism. AB - In order to evaluate the possible role of genetic factors in the pathogenesis of congenital hypothyroidism (CH), we investigated the occurrence of chromosome aberrations in a consecutive series of 47 patients with CH and 208 matched healthy controls. No abnormal karyotype was found in CH patients. In 5 CH patients and in 3 healthy controls a number of heterochromatin variants was detected. Although chromosomal variants are devoid of phenotypic effects, the frequency of these variants was higher in CH patients than in the control group (10.6% vs 1.4%, p less than 0.005). These findings suggest that the association of congenital hypothyroidism with chromosomal variants may reflect more than chance concurrence. PMID- 2229933 TI - Lack of expression of antigens for islet cell antibodies in rat fetal pancreas. AB - It is not clear yet when pancreatic islet cells begin to express antigens for islet cell antibodies (ICA). Therefore, we studied whether human ICA-positive sera, crossreacting with adult rat islet cells, react with fetal and neonatal rat islet cells immunohistologically. The ICA did not react with fetal islet cells. On the other hand, neonatal islet cells over 2-3 weeks of age expressed the reactivities almost similar to those of the adult. It was suspected that pancreatic islet cells started to express their antigens to induce ICA gradually after birth. PMID- 2229935 TI - A possible association between cyclic disorder of glucose metabolism and adrenal medullary hyperplasia. PMID- 2229937 TI - Biomarkers of aging: do we know what to look for? AB - The identification of specific biomarkers of aging would be an important milestone in gerontologic research. In this communication, the goals of identifying biomarkers of aging are summarized and some criteria for defining biomarkers are suggested. An age-related alteration in a biological parameter is not necessarily a biomarker of aging. None of the previously observed age-related changes satisfies all the criteria. Potential biomarkers that are applicable to human aging include in vitro proliferative capacity of fibroblasts, glycation of collagen, and DNA unwinding rate. Future research should focus on identifying age related changes that are not merely expressions of aging, but also have some causal link to aging. PMID- 2229938 TI - Can an index of aging be constructed for evaluating treatments to retard aging rates? A 2,462-person study. AB - Biomarkers of aging are needed to evaluate proposed treatments to retard aging rates. At present, the only validated biomarker of aging is maximum life span, which remains impractical for human use. Identification of other biomarkers awaits development of a method of biomarker validation. This paper outlines an approach for this purpose intended for selecting biomarkers usable in humans. Prospective biomarkers are validated and weighted according to their correlation with interventions that, in healthy individuals, influence life span, namely mortality risk factors. A general mathematical method is presented for combining biomarker scores into an index of aging rate. This method addresses problems encountered with the traditional (multiple regression) method of calculating biological age and develops an index termed standardized biological age, SBA. In applying the method to 2,462 office workers, SBA, based on 12 physiological tests under investigation as biomarkers of aging, was found to depend on most of 17 surveyed dietary, exercise, life style, and geographical risk factors for mortality or health, suggesting that many risk factors predict rates of common functional declines with age. The 12 candidate biomarkers of aging in this study differed widely in validity according to the criterion employed. The approach holds promise for assembling an experimentally useful battery of biomarkers of aging. PMID- 2229936 TI - Recent advances in the human physiology of inhibin secretion. PMID- 2229939 TI - Metabolic heat production during repeated cold stress in adult and aged male C57BL/6J mice. AB - Adult and aged male C57BL/6J mice were subjected to three consecutive 3-hour cold stress tests (partial physical restraint at 6 degrees C), repeated 2 weeks apart. Body mass and colonic temperature were measured before each test, and colonic temperature, O2 consumption, and CO2 production were measured during cold exposure. The slopes of colonic temperature and heat production and the mean metabolic heat production were calculated for each animal. Adult mice showed stronger cold tolerance compared to aged mice and also exhibited habituation to cold exposure (improvement of cold tolerance with repeated tests). Mean metabolic heat production during cold exposure was greater in adult mice, and only adults demonstrated significant increases across tests in both metabolic heat production and slope of metabolic heat production over time. We hypothesize that reduced cold tolerance in aged mice is related mainly to a decrease in metabolic heat production. Increased metabolic heat production in subsequent tests in adults is a probable mechanism for habituation to repeated cold exposure. PMID- 2229940 TI - Body fat distribution in healthy young and older men. AB - Central and/or intraabdominal (IA) fat is an independent predictor of obesity related metabolic abnormalities in young and middle-aged subjects. The elderly are "fatter" at any given relative weight and often have similar metabolic abnormalities. In this study we compare body composition, circumferences, and specific fat depots areas in a population of healthy young and older men. Although the two groups were similar in body mass index and percent body fat, their distribution of adiposity was different. The young subjects had 16% and 10% larger thigh (p = .0001) and arm (p less than .01) circumferences respectively, while the ratio of waist-to-hip circumference was greater in the older subjects (0.93 +/- 0.04 vs 0.97 +/- 0.04, p = less than .01). The most striking differences between the groups were noted on computed tomography, with a twofold greater IA fat area (72.6 +/- 38.2 vs 143.6 +/- 56.2 cm2, p less than .0001), and a twofold lesser thigh subcutaneous fat area (156.3 +/- 69.3 vs 82.4 +/- 29.7 cm2, p less than .001) in the older subjects. We conclude there is an age-related central and intraabdominal redistribution of adipose mass, even in healthy older subjects. Since these changes occur in the absence of clinical disease, the associations between metabolic abnormalities and a central and or IA distribution of adiposity in the elderly must be investigated further. PMID- 2229941 TI - Functional reach: a new clinical measure of balance. AB - A new clinically accessible measure of balance, functional reach (FR), is the difference between arm's length and maximal forward reach, using a fixed base of support. The purposes of this study were to (a) establish FR as a measure of the margin of stability versus the laboratory measure, center of pressure excursion (COPE); (b) test reliability and precision, and (c) determine factors that influence FR, including age and anthropometrics. We evaluated FR in 128 volunteers (age 21-87 years). FR was determined with a precise electronic device and a simple clinical apparatus (yardstick). FR correlates with COPE (Pearson r = .71) and is precise (coefficient of variation = 2.5%) and stable (intraclass correlation coefficient across days = .81). Age and height influence FR. FR is portable, inexpensive, reliable, precise, and a reasonable clinical approximator of the margin of stability. FR may be useful for detecting balance impairment, change in balance performance over time, and in the design of modified environments for impaired older persons. PMID- 2229942 TI - Cholesterol screening in 5,719 self-referred elderly subjects. AB - To assess the frequency of hypercholesterolemia as a potential major public health problem in the elderly, we studied 5,719 self-referred subjects greater than age 60 and 11,890 less than or equal to 60 years, whose nonfasting capillary blood cholesterol levels were measured during an 18-month screening in Cincinnati area grocery stores. We followed National Cholesterol Education Program guidelines for serum cholesterol (less than 200 mg/dl "desirable," 200-239 "borderline-high," and greater than or equal to 240 mg/dl "high"). Of 4,011 61-70 year-olds, only 19% had capillary blood total cholesterol less than 200, 38% were 200-239, and 43% greater than or equal to 240 mg/dl. Of 1,493 aged 71-80 years, only 20% had total cholesterol less than 200, 36% had levels 200-239, and 44% were greater than or equal to 240 mg/dl. In 215 subjects, 81 and over, 29% had total cholesterol less than 200, 36% were 200-239, and 35% were greater than or equal to 240 mg/dl. Application of the non-age, non-race, non-sex specific National Cholesterol Education Program guidelines to the elderly may necessitate followup and perhaps therapy in 71-81% of subjects, suggesting that the appropriate intervention approach be general population-oriented, rather than the individual detection, diagnosis, and treatment approach which presents a huge, expensive load for a relatively unprepared health care community. PMID- 2229943 TI - Musculoskeletal impairments and physical disablement among the aged. AB - This article summarizes the results of a longitudinal investigation of the progression of sight, hearing, and musculoskeletal impairments and their association with change in physical disability, in 10 ADLs among members of the Massachusetts Health Care Panel Study. The findings confirm widely held clinical beliefs that specific types of musculoskeletal decrement are an important cause of physical disability among older persons. Decrement in hand function is a significant musculoskeletal impairment influencing limitations in Basic ADL, and progression of Instrumental ADL dysfunction is influenced by progression of lower extremity impairments. Progression of sight and hearing impairments was not associated with change in physical disability. Musculoskeletal impairments, one of the most prevalent and symptomatic chronic complaints of middle and old age, deserve increased attention from epidemiologists, disability researchers, and clinicians seeking ways to prevent disablement among the aged. PMID- 2229944 TI - Hypertension and acculturation in elderly Mexican Americans: results from 1982-84 Hispanic HANES. AB - The purpose of our study was to describe the relationship between acculturation and hypertension in elderly Mexican Americans. Two age groups, 55-64 and 65-74, were examined from data provided in the Hispanic Health and Nutrition Examination Survey (HHANES). The prevalence of hypertension among subgroups of different acculturation was ascertained based on the modified Cuellar Acculturation Scale. Each age group was also stratified using the HHANES poverty index, with those above the index compared to those below. A stepwise logistic regression was performed among the variables of poverty, gender, age, and acculturation in relation to hypertension. The results indicate that acculturation and age are stronger predictors of hypertension than poverty in elderly Mexican Americans, with acculturation being a stronger predictor among those age 55-64. Factors related to acculturation may have a stronger influence on the prevalence of hypertension in older Mexican Americans than differences related to socioeconomic status. PMID- 2229945 TI - Recognizing and naming faces: aging, memory retrieval, and the tip of the tongue state. AB - Subjects over the age of 50 were presented with famous and nonfamous male faces. If they recognized the face, they were asked for his name and for as much information about the person as possible. For recognition, older subjects were less sensitive (lower d-prime) and more cautious (higher beta) than younger subjects. The number of "tip of the tongue" (TOT) naming responses as a proportion of faces recognized increased with age, while the number of responses where the right name was produced correspondingly decreased with age. Following responses of No, TOT, and Yes to "Do you know his name?", older subjects reported fewer correct semantic features than younger subjects in all three cases; but as proportions of the number of correct semantic features following Yes responses, there were no age effects (.21 and .59 for No and TOT responses, respectively). In multiple regression analyses, age surprisingly was often a better predictor of performance than measures of current cognitive ability. The results are interpreted as evidence of impairment with age associated with at least three stages in the face recognition process as identified by Bruce and Young (1986). PMID- 2229946 TI - The effects of memory skills training and incentives on free recall in older learners. AB - The impact of memory skills training and external reward on free recall of serial word lists was assessed in 60 elderly community-dwelling adults. Participants were divided into four groups: (a) skills training plus incentive, (b) skills training only, (c) placebo plus incentive, and (d) placebo without incentive. The memory skills training involved 2 hours of class instruction and a take-home manual. The incentive was introduced following the posttest study interval, prior to recall, and was in the form of a lottery. The three experimental groups (skills only, skills plus incentive, and incentive only) recalled more words at the posttest interval than the placebo group. Skills training was associated with the greatest number of words recalled, followed by the incentive. No additional performance gains were found when skills training was coupled with incentive. A significant relationship between study time and word recall performance was found at posttest. Those who received skills training used more study time than did the no skills groups. The results suggest that teaching an active memory skill enhances free recall performance. Additionally, incentives were superior to no training. Combining incentives with skills, however, does not extend memory performance over skills training alone. PMID- 2229947 TI - The game of bridge as an exercise in working memory and reasoning. AB - Fifty bridge players and 50 nonplayers, between the ages of 55 and 91, were given tests of working memory, reasoning, reaction time, and vocabulary. Data were analyzed using multivariate and univariate analyses of variance with age as a covariate. Results indicated that the players outperformed nonplayers in measures of working memory and reasoning, but not vocabulary and reaction time. Results were consistent with the hypothesis that bridge, which provides specific experience in working memory and reasoning, should enhance performance in tasks tapping these abilities and not enhance performance in unrelated abilities. Because the data were correlational, the rival hypothesis that bridge playing selects for individuals who perform better at working memory and reasoning tasks could not be rejected. PMID- 2229948 TI - Falls efficacy as a measure of fear of falling. AB - We developed the Falls Efficacy Scale (FES), an instrument to measure fear of falling, based on the operational definition of this fear as "low perceived self efficacy at avoiding falls during essential, nonhazardous activities of daily living." The reliability and validity of the FES were assessed in two samples of community-living elderly persons. The FES showed good test-retest reliability (Pearson's correlation 0.71). Subjects who reported avoiding activities because of fear of falling had higher FES scores, representing lower self-efficacy or confidence, than subjects not reporting fear of falling. The independent predictors of FES score were usual walking pace (a measure of physical ability), anxiety, and depression. The FES appears to be a reliable and valid method for measuring fear of falling. This instrument may be useful in assessing the independent contribution of fear of falling to functional decline among elderly people. PMID- 2229949 TI - The meaning of grandparenthood and its relationship to demographic, relationship, and social participation variables. AB - The meaning of grandparenthood has been a focus of research, especially during the last decade. Types of meanings and variables differentiating these grandparental meanings have been established. Most recently Kivnick (1981, 1982a, 1982b, 1985) has derived a multidimensional framework representing five aspects of the meaning of grandparenthood. The present study attempted to verify whether these five aspects of meaning were related to unique combinations of demographic, social, personal, and health variables. Zero-order correlations showed high intercorrelations among Kivnick's five subscales, and low correlations among the majority of variables. Regression analyses indicated that no more than 30% of the variance in any one of the dimensions could be explained and that considerable overlap existed in the significant predictors across aspects of meanings. PMID- 2229950 TI - Family, households, and care arrangements of frail older women: a structural analysis. AB - Previous research has examined determinants of the living arrangements and the informal-care arrangements of older women; research on care arrangements has often taken living arrangements as given. Here we consider each separately, then go on to analyze the simultaneous determinants of living and care arrangements. Factors influencing these outcomes can be categorized as indicators of opportunities, resources, needs, or preferences. Of particular interest is the extent to which kin availability--specifically, the existence of living children- constrains opportunities, the role of financial resources, and the consequences of needs as revealed by levels of physical and mental disability. Our analysis consists of multinomial-logit models estimated with data from the 1982 National Long-Term Care Survey. The results indicate the importance of kin availability, with striking differences in the living and care arrangements between childless and other older women. Among those with children, there are less striking but consistent differences according to the number and sex composition of living children. Finally, variables representing needs for care are generally the strongest predictors of all the outcomes analyzed. PMID- 2229951 TI - Risk factors for nursing home admissions and exits: a discrete-time hazard function approach. AB - Discrete-time hazard functions were estimated to determine factors associated with the probability of admission to a nursing home from the community, and the probability of discharge to the community from nursing home care, for 3,332 individuals enrolled in The National Long Term Care Channelling Demonstration. This was a relatively frail elderly population assessed to be at high risk for nursing home use. In predicting admissions, major factors were found to be ethnicity (Blacks and Hispanics were at much lower risk), homeownership, advancing age, living alone, exhibiting higher cognitive and functional impairment levels, physician use, and living in an area with a larger nursing home bed supply. The probability of being discharged alive was predicted by several factors, including ethnicity (Blacks being less likely to be discharged), homeownership, being of younger age, better (self-rated) health, functional and cognitive capacities, and medical acuity. PMID- 2229952 TI - Predictors of institutionalization among Alzheimer disease victims with caregiving spouses. AB - A theoretical model predicting "desire to institutionalize" and actual institutionalization was developed and tested on a sample of 220 persons caring for a demented spouse. Significant predictors of "desire to institutionalize" include age and education of caregiver, spouse's forgetful behaviors, ADL tasks done by the caregiver, medications taken by the caregiver, services used, and quality of relationship with spouse. Predictors of actual institutionalization are desire to institutionalize, length of time spent as a caregiver, religion, uplifts, and forgetful behaviors of the impaired spouse. PMID- 2229953 TI - Strain, social support, and mental health in rural elderly individuals. AB - This study examined the relationships among social support, life strain, and mental health in a sample of 210 rural elderly individuals. Life strain was operationalized as economic deprivation, illness disability, and ADL impairment. Demographic characteristics had little effect on mental health. Physical health status was highly predictive of life satisfaction and psychological distress among rural elderly individuals. Disability associated with chronic illness and ADL impairment was related to increased reports of symptoms of emotional and psychosomatic distress. Measures of social contacts and instrumental support exerted small to moderate effects on life satisfaction, psychosomatic distress, and emotional distress. Affective support moderated the effects of health-related strain on mental health. PMID- 2229954 TI - Are they ready? Discharge planning for older surgical patients. AB - 1. With ever-increasing cost containment, patients are being discharged from the hospital earlier. 2. The majority (96%) of elderly patients (average age 70 years) in this study, after abdominal and cardiac surgery, thought they were ready to be discharged. 3. Surgical patients' level of functional ability was significantly improved from predischarge to postdischarge. There were no significant differences in their pain, strength, knowledge, and mood levels. 4. Predominantly non-nursing functions (eg, transportation, housekeeping) were identified as areas of needed help at home for elderly patients after surgery. PMID- 2229955 TI - Exploring the roles of men. Caring for demented relatives. AB - 1. Men are under-represented among family members providing care to a demented relative. 2. Few differences were noted among the male caregivers: men with demented relatives at home spent more time daily on caregiving tasks although both groups of men tended to rely on others for the "hands-on" care needed; institutionalized demented relatives were rated as being more impaired than those at home; and men caring for relatives at home seemed determined to continue in their role. 3. It is possible that men find it more difficult to become caregivers because of lack of support from other family members, the impairment of the relative and the need for direct care, and men's lack of involvement in providing direct care. 4. Nurses involved in dementia care should offer instructional sessions aimed at men, provide assistance in working through emotional problems, and encourage their participation in future research on the male caregiving experience. PMID- 2229956 TI - Oxygen saturation levels in the well elderly: altitude makes a difference. AB - 1. A reduction in oxygenation indicated by a lower PO2 and O2 saturation is a normal part of aging, but a change in carbon dioxide level is considered to reflect pulmonary disease. 2. The oxygen saturations of the well elderly living at moderate altitude and those living at low altitude were at the lower limits of normal for their respective altitudes. 3. Well elderly living at moderate altitude had an oxygen saturation that was significantly lower than the oxygen saturation of the people living at sea level. 4. Because of the wide range of oxygen saturation levels that exist in normal individuals, it is important to evaluate changes in oxygen saturation against the person's own level. PMID- 2229957 TI - Night life: nocturnal behavior patterns among hospitalized elderly. AB - 1. In contrast to previous studies where elderly living in an institution were found to demonstrate a consistent, predictable pattern of nocturnal activity, hospitalized elderly were found to be asleep less and awake more over a period of 3 consecutive nights. 2. Medication, treatments, and assessment were scheduled with little regard for the hospitalized elderly's need for restorative sleep. 3. Each time an elderly patient was awakened, it took him or her at least 30 minutes to return to sleep. 4. Nurses are advised to determine and maintain as much as possible the patient's usual bedtime routine, keep interruptions during the night to a minimum, schedule medications and treatments efficiently, decrease noise, and medicate for pain as appropriate. PMID- 2229958 TI - Restraint-free care: is it possible? PMID- 2229959 TI - Using mental health principles as we age. PMID- 2229960 TI - Estrogen replacement therapy. AB - 1. Menopause, defined as the permanent cessation of menstruation resulting from loss of cyclic ovarian function, occurs spontaneously at a mean age of 51 years. More than 40 million American women are postmenopausal, and an additional 30 million are expected to join their ranks during the next decade. 2. The depletion of naturally occurring hormones that accompanies menopause and the issue of hormone replacement therapy have become fundamental concerns in women's health care. 3. Many experts now advise estrogen-progestin replacement therapy to prevent osteoporosis in all women at high risk for this disorder, and for vasomotor flushes, genitourinary symptoms, and mood changes in women who have no contraindication to this therapy. 4. Hormone replacement therapy plays a pivotal role in preserving good health and vitality, but it should be presented within the context of other health-promoting measures to be adopted by menopausal and postmenopausal women. PMID- 2229961 TI - A role delineation study of hand surgery. AB - In 1986, The American Association for Hand Surgery and the American Society for Surgery of the Hand jointly sponsored a Role Delineation Study of Hand Surgery. The purpose of this study was to define the knowledge and skills necessary for competent hand surgery practice and to determine the responsibilities and activities of hand surgeons. Eight hundred thirty-eight hand surgeons returned a self-report questionnaire. This questionnaire was designed to collect information relative to the demographic characteristics of the respondents, the importance of 38 surgical procedures, and 60 categories of knowledge related to hand surgery, and to elicit respondents opinions regarding certification in hand surgery. This study is a first attempt to define the domain of hand surgery. The data collected in this study provide the basis for designing residency fellowship and continuing education programs and may also be used to study manpower needs, regional variations in practice patterns, and to identify the educational needs of the profession of hand surgery. PMID- 2229962 TI - Scapholunate interosseous reconstruction and imbrication of palmar ligaments. AB - Twenty-eight patients with scapholunate interosseous ligament disruption, carpal instability, and persistent wrist pain were treated by carpal reduction, stabilization, and palmar ligament reconstruction. In twenty-two of these patients pain was well controlled, carpal alignment was maintained, and they were able to resume their previous employment. Grip and pinch strengths averaged eighty-two percent and range of motion averaged seventy-six percent of the normal uninvolved side. PMID- 2229963 TI - Scapholunate dissociation in the skeletally immature carpus. AB - A case of scapholunate dissociation with a dorsal carpal instability pattern is described in a skeletally immature 13-year-old male. The malrotation of the scaphoid was treated by soft tissue reconstruction, with use of a dorsal capsulodesis to provide a dorsal restraint to excessive palmar flexion of the scaphoid. In the skeletally immature carpus, isolated ligamentous injuries are less frequently recognized than epiphyseal injuries. To avoid interference with the successful conclusion of carpal growth, soft tissue reconstruction of deranged carpal relationships is preferable to intercarpal arthrodesis in the skeletally immature patient. PMID- 2229964 TI - Failure of trapeziometacarpal arthrodesis with use of the Herbert screw and limited immobilization. AB - Eighteen patients with trapeziometacarpal joint arthritis had arthrodesis with use of the 1.9 mm Herbert screw for internal fixation. Thumb spica cast immobilization was maintained for an average of 8 weeks, followed by thumb spica orthoplast splintage on a part time basis. Fourteen patients had radiographic follow-up an average of 12 months after operation. Seven had union and seven had a nonunion. There were three fixation-related complications and two nonfixation related complications. Eleven patients had clinical follow-up an average of 12 months after operation. Four patients had no pain, five had mild pain, and two had moderate pain after operation. All had severe pain before operation. All were satisfied with the procedure. Although subgroups of patients had a higher rate of union with bone grafts or with immobilization over 8 weeks, the theory that arthrodesis with 1.9 mm Herbert screws does not require external splintage and allows early mobilization is not supported by this series. PMID- 2229965 TI - Ulnar styloid fixation in the treatment of posttraumatic instability of the radioulnar joint: a biomechanical study with clinical correlation. AB - Biomechanical displacement testing was done on nine fresh human upper extremities to define the stabilizing influence of the triangular fibrocartilage on the radioulnar joint and the efficacy of triangular fibrocartilage-ulnar styloid avulsion fracture repair in restoring lost stability. Test data confirmed that the triangular fibrocartilage is a major stabilizer of the radioulnar joint and internal fixation of triangular fibrocartilage-ulnar styloid avulsion fractures can restore preavulsion stability in all positions of forearm rotation. On the basis of this data and a successful clinical experience, primary repair of displaced ulnar styloid avulsion fractures is advised as a means of stabilizing the radioulnar joint and preventing the disability associated with chronic radioulnar joint instability. PMID- 2229966 TI - Effects of distal radius fracture malunion on wrist joint mechanics. AB - An experimental model using a static positioning frame, pressure-sensitive film (Fuji), and a microcomputer-based videodigitizing system was used to measure contact areas and pressures in the wrist. Contact areas and pressures were compared in a group of wrists between the normal state and with simulated distal radius fracture malunions of varying degrees. In simulated malunions, radial shortening to any degree slightly increased the total contact area in the lunate fossa, and was significant at 2 mm of shortening. By angulating the distal radius more than 20 degrees either palmar or dorsal, there was a dorsal shift in the scaphoid and lunate high pressure areas, and the loads were more concentrated, but there was no change in the load distribution between the scaphoid and lunate. Decreasing the radial inclination shifted the load distribution so that there was more load in the lunate fossa and less load in the scaphoid fossa. PMID- 2229967 TI - Effects of radioulnar instability on the radiocarpal joint: a biomechanical study. AB - Five fresh cadaver upper extremities were studied with use of a static positioning frame, pressure-sensitive film and a microcomputer-based videodigitizing system to assess the effect of increasing radioulnar instability on the load distribution within the proximal carpal joint. Three stages of radioulnar instability were studied: (1) an avulsion fracture at the base of the ulna styloid; (2) an avulsion fracture at the base of the ulna styloid plus disruption of the dorsal portion of the distal radioulnar joint capsule; and (3) an avulsion fracture at the base of the ulna styloid, disruption of the dorsal portion of the distal radioulnar joint capsule, and disruption of the radioulnar interosseous membrane. All stages of radioulnar instability demonstrated a decrease in the lunate contact area in positions with the forearm in supination. In stage 3 instability there was also less lunate contact area in positions with the forearm in neutral pronation/supination. In stage 3 instability the lunate high pressure area centroid was abnormally palmar in all positions and the scaphoid high pressure area centroid was abnormally palmar in positions with the forearm in pronation or supination. PMID- 2229968 TI - Results of dorsal wrist synovectomies in the rheumatoid hand. AB - Seventy-eight patients with rheumatoid arthritis had 102 dorsal wrist tenosynovectomies, intraarticular synovectomies, and Darrach resection from 1962 to 1982. Follow-up after surgery averaged 11 years, with a range from 3 to 20 years. Pain was diminished in all but 17 wrists and motion decreased an average of 13 degrees. Synovitis recurred in 16 wrists and x-ray evidence of progressive intraarticular destruction was seen in 45 wrists. Revision surgery was necessary in 28 wrists. PMID- 2229969 TI - Type IV flexor digitorum profundus avulsion. AB - Flexor digitorum profundus avulsions, are well-documented injuries occasionally associated with a distal phalanx fragment. While the injury may involve primarily either tendon or bone, a rarely observed variant combines both tendon and bone avulsions. A type IV variant seen after two sequential injuries is described. PMID- 2229970 TI - Flexor tendon ruptures secondary to hamate hook fractures. AB - Four patients with flexor tendon ruptures secondary to hook of the hamate fracture are described. None of the patients had the diagnosis of fracture made before tendon rupture. All patients were treated with excision of the fractured hook and tendon repair. The tendon repair was usually an end-to-side (Y junction) of the profundus of the small to the profundus of the ring finger. After operation, all patients were free of pain and returned to their preinjury activity levels, but most had some limitation of motion in the digit with the tendon repair. The complication of tendon rupture not uncommonly follows basilar hook of the hamate fractures. Treatment by excision of the fracture and end-to side tendon repair produces satisfactory results. Range of motion after tendon repair seems to depend more on the patient's age and the amount of inflammation at the site of repair rather than on the method of tendon repair. PMID- 2229971 TI - Closed traumatic rupture of the ring finger flexor tendon pulley. AB - We report an unusual case of closed traumatic rupture of the ring finger flexor tendon pulley not previously reported in the literature. This injury occurred in a 21-year-old athlete during rockclimbing. Lack of flexion of the distal interphalangeal joint was accompanied by a palpable subcutaneous cord on the palmar side of the proximal phalanx. A simple repair of the pulley was done. The postoperative functional result was satisfactory. PMID- 2229972 TI - Treatment of trigger finger by steroid injection. AB - A retrospective study of 235 patients with 338 primary trigger fingers determined the efficacy and safety of steroid injection. Initial treatment consisted of one to three injections of corticosteroid mixed with local anesthetic. Those fingers that failed injection therapy had conventional release of the first annular pulley. Seventy-seven percent of all fingers showed resolution or improvement; 49% after a single injection, 23% after two injections, and 5% after three injections. PMID- 2229973 TI - Unilateral osteonecrosis in a patient with bilateral os centrale carpi. AB - Accessory carpal bones, although uncommon, are usually of no clinical significance. This report describes a patient who had bilateral presence of the accessory bone called the os centrale carpi. The patient was seen with disabling pain in the dominant right wrist and both radiologic and pathologic findings showed osteonecrosis and secondary degenerative arthritis. His left wrist was asymptomatic and the accessory ossicle was normal in appearance. We have not been able to discover any cases in the literature describing the development of unilateral osteonecrosis in a patient with bilateral os centrale capri. PMID- 2229974 TI - Fasciectomy for treatment of Dupuytren's disease and early complications. AB - This review of 103 cases of hands operated on for treatment of Dupuytren's disease demonstrates the significant increase of postoperative stiffness as related to recurrences and staging of the disease, but not to sex. On the contrary, the frequency of reflex sympathetic dystrophy after fasciectomy is sex related affecting females. The protective effect of guanethidine may be a valuable therapeutic adjunct for female patients. We propose that the disease be staged on the basis of anatomic findings, inasmuch as staging based on degree of contracture alone is insufficient for comparative studies. PMID- 2229975 TI - Role of antibiotics in open fractures of the finger. AB - The role of antibiotics was investigated prospectively in 91 open fractures of the finger. Antibiotics were administered to alternate patients with open phalangeal fractures. Only finger fractures distal to the metacarpophalangeal joint were included. Both groups were treated with aggressive surgical irrigation and debridement. In four patients in each group clinical signs of infection eventually developed; osteomyelitis did not develop in any patients, and no secondary surgical procedures were required in either group. This data indicates that vigorous irrigation and debridement is adequate primary treatment for open phalangeal fractures in fingers with intact digital arteries. PMID- 2229976 TI - YAG laser resection of complicated hemangiomas of the hand and upper extremity. AB - Complicated hemangiomas of the hand or upper extremity have been resected in eight patients with use of the YAG laser with sapphire scalpels. This laser allows excellent hemostasis and precise surgery, thus allowing resection of complicated problems. Many of the patients have had preoperative arteriography with selective embolization, which has aided in hemostasis. Almost complete but subtotal resection of hemangioma was possible in four of the eight patients with well localized lesions. Three patients had only partial resections of hemangiomas and one lesion was considered unresectable. PMID- 2229977 TI - Thrombosis of the vena comitantes of the ulnar artery. AB - A case of traumatic aneurysm of the vena comitantes of the ulnar artery is reported, which was seen initially as a painful hypothenar mass after blunt trauma. Ligation and excision produced complete relief without recurrence. PMID- 2229978 TI - Fractures of the sesamoid bones of the thumb. AB - Sesamoid fractures of the metacarpophalangeal joint of the thumb may be classified into two types: (1) with palmar plate intact, and (2) with palmar plate ruptured. In type 1, the patient maintains a normal flexion posture of the metacarpophalangeal joint as well as the ability to flex the metacarpophalangeal joint and interphalangeal joint. In type 2, the metacarpophalangeal joint assumes a hyperextension posture and the patient is unable to flex the metacarpophalangeal joint. Three cases are described to illustrate the two types of the injury. An open fracture of a thumb sesamoid associated with laceration of the palmar plate in a child was treated by reapproximating the palmar plate and the fracture fragments with sutures. Two additional closed fractures of the thumb sesamoid were treated by splinting the metacarpophalangeal joint in comfortable flexion for 2 to 3 weeks. Normal hand function was restored in all the three patients. PMID- 2229979 TI - Pathologic fracture of the proximal ulna through a bone graft donor site. AB - Complications of harvesting autologous bone graft from the iliac crest and tibia are well known; exclusive use of upper extremity donor sites in hand surgery has therefore been advocated. Six weeks of postoperative elbow splinting has been recommended after harvest of large proximal ulnar grafts. We report two cases of pathologic fracture of the proximal ulna complicating local bone grafting and question whether the risk of fracture and the attendant patient inconvenience and potential joint stiffness incurred by postoperative immobilization are exceeded by the morbidity of carefully done iliac crest grafting. PMID- 2229980 TI - The nerve of Henle. AB - The nerve of Henle, a branch of the ulnar nerve in the forearm, is thought to deliver sympathetic innervation to the ulnar artery. Forty cadaver forearms were dissected under magnification. Two distinct patterns of the nerve were found. In the typical pattern, 18 (45%) of 40 extremities, the nerve originates 16 cm proximal to the ulnar styloid, travels distally with the ulnar artery, and frequently, 13 (72%) of 18, branches to pierce the superficial fascia 6 cm proximal to the ulnar styloid and innervate the skin of the distal ulnar forearm. In the atypical pattern (12%), the nerve originates in the distal 8 cm of the forearm and travels briefly with the ulnar artery before branching to the skin. The palmar cutaneous branch of the ulnar nerve was absent in cadavers with the nerve of Henle and may be a distal variant of that nerve. PMID- 2229982 TI - Local neurovascular island flap. AB - Fingertip amputation, with loss of the terminal pulp and bone exposure presents a difficult problem. Reconstruction with use of a local neurovascular island flap has been done in twenty-one patients to restore sensibility and function with preservation of length. All patients achieved two-point discrimination values within two millimeters of the normal contralateral fingertip, with adequate pad for pain-free pinch. We advocate this procedure for deep pulp loss over the distal phalanx. It is reliable, single-staged, and provides skin coverage closer to normal than any regional flap technique. PMID- 2229981 TI - Multifocal neurilemomas in different nerves of the same upper extremity. AB - We report a case of multifocal neurilemomas originating from different nerves in the same upper extremity. In the excision of all seven tumors care was taken not to damage the nerves involved. The common features of multifocal neurilemomas that originated from different nerves of the same upper extremity are outlined and the consequent risk of potential nerve damage during the operation is discussed. We recommend intracapsular excisions of multifocal neurilemomas. PMID- 2229983 TI - The evolution of carpal nomenclature: a short review. PMID- 2229984 TI - Improved ORS formulations. PMID- 2229985 TI - Fatal dysentery in rural Bangladesh. AB - The purpose of this study was to find out the actual circumstances which lead to dysentery-related deaths in the rural Bangladesh. The Community Health Workers of the International Centre for Diarrhoeal Disease Research, Bangladesh have been collecting records of all deaths at the rural area of Matlab through a surveillance system since 1963. A review of existing data on dysentery-related deaths from this area during 1976-1981 suggests that deaths in children followed a recurring seasonal pattern with an increase during the post-monsoon season of August-November of each year. This seasonal pattern of death was not evident among adults. The overall dysenteric death rate during 1978-1981 was 13.3 per 10,000 population per year. The highest rates were in patients of the two extreme age groups. Deaths reported recently by the health workers were re-investigated. Although the causal agents producing fatal dysentery in most patients in the community remained unidentified, it was likely to be species of Shigella in childhood deaths. To identify clinical determinants of a fatal outcome, a case control analysis was done with patients hospitalised with dysentery in 1980. The risk factors shown to be significantly associated with deaths were: longer median duration of illness (p = less than 0.001), female sex (p = 0.039), signs of respiratory infection (p = less than 0.001) and severe malnutrition (p = 0.002). PMID- 2229986 TI - Feasibility of home treatment of diarrhoea with packaged rice--ORS. AB - Feasibility of home treatment of diarrhoea with packaged rice-based oral rehydration salts (R-ORS) was compared, in terms of cost, with that for glucose based oral rehydration salts (G-ORS). Packets of G-ORS (World Health Organization recommended composition) were distributed in two Bangladeshi villages (G-ORS area). Packets of R-ORS with similar composition, except that glucose was replaced with rice flour (50 g/l), were distributed in other two villages (R-ORS area). During the 7-month study period, 1061 and 1348 diarrhoeal episodes were detected among 409 under-five children in each of the study areas. R-ORS was used, either alone or in combination with drugs, to treat 662 (62%) episodes in the R-ORS area, compared to 1101 (82%) episodes in the G-ORS area. The treatment cost per episode was more with R-ORS than with G-ORS, though fewer R-ORS packets were used per episode. Among others, the main factor for the higher cost was found to be the higher production cost of R-ORS packets. Expected early recovery from diarrhoea with use of R-ORS was not observed in this study. Under the study situation, the feasibility of home treatment of diarrhoea with packaged R-ORS was not apparent. PMID- 2229987 TI - Clinical and epidemiological features of sporadic infections with Vibrio fluvialis in Florida, USA. AB - The clinical and epidemiological features of sporadic illness were investigated in 12 persons from whom Vibrio fluvialis was recovered and who were reported to the Florida Department of Health and Rehabilitative Services between 1982 and 1988. All 12 patients lived in Florida and denied any recent travel out of the state prior to the onset of their illness. V. fluvialis was recovered from the stools of 10 patients who presented clinically with gastroenteritis, from a wound in one patient, and from a caecostomy drainage specimen in one patient. Eight of the 10 patients with gastroenteritis reported eating seafood during the week before becoming ill: raw oysters (five patients), shrimp (two patients), and cooked fish (one patient). This represents the largest clinical series of V. fluvialis cases described in the United States. PMID- 2229988 TI - The zymodemes of Entamoeba histolytica in New Delhi, India. AB - The prevalence of various pathogenic and non-pathogenic zymodemes of Entamoeba histolytica in New Delhi, India was studied by characterising its isoenzyme patterns. Non-pathogenic zymodeme I was found to be most common and was detected in 39 of 49 infections. The other non-pathogenic zymodemes detected were XVII and XVIII in two cases each. The pathogenic zymodemes detected were II (four cases), II alpha- (alpha) (one case) and XIV (one case). Approximately 72% of those harbouring non-pathogenic zymodemes and 33% of those harbouring pathogenic zymodemes were asymptomatic. All the symptomatic individuals harbouring non pathogenic zymodemes were seronegative for amoebiasis. However, subjects harbouring pathogenic zymodeme but asymptomatic were seropositive for amoebiasis at a titre of greater than 1:80, indicating a past infection or subclinical tissue invasion by the parasite. The new zymodeme isolated from a case of acute dysentery was designated II alpha- on the basis of the banding pattern of the enzyme glucose phosphate isomerase. PMID- 2229989 TI - Prevalence of Campylobacter infections in animals and children in Haryana, India. AB - To study the prevalence of infections with Campylobacter spp in Haryana, India, a stool sample was collected using a rectal swab from 30 buffaloes, 62 cattle, 95 pigs and 94 children and was bacteriologically cultured. The subjects were either apparently healthy or had diarrhoea. The organisms were isolated in a medium containing reducing agents and antibiotics, and culture plates were incubated in a candle jar at 42 degrees C. 63% of all thermophilic Campylobacter were cultured from rectal swabs taken from young livestock and children with diarrhoea. Of 32 isolates fully identified, 23 were C. jejuni, 8 were C. coli and 1 was C. laridis. The C. jejuni isolates belonged to the Lior's biotype II. PMID- 2229990 TI - Crohn's disease: what about the pancreas? AB - Crohn's disease (CD) is now accepted as a systemic illness. The importance of extraintestinal manifestations is underlined by the fact that such "complications" can be more prominent and even more difficult to control than the intestinal disease itself. Lately, evidence for a more than accidental association of pancreatitis and exocrine pancreatic insufficiency with CD is growing. This might have a significant impact on the treatment of abdominal pain and diarrhea in CD, symptoms which have so far been attributed exclusively to the intestinal rather than the extraintestinal manifestations of the disease. PMID- 2229991 TI - Oncogenes and suppressor genes: their involvement in colon cancer. AB - Abnormalities in oncogenes, which are broadly classified into viral and cellular oncogenes, and suppressor genes appear critical for the development of colon cancer. Cellular oncogenes contribute to malignant transformation when they become activated by point mutation, translocation, amplification, or loss of regulator sequences. The properties of the oncoproteins, the proteins encoded by oncogenes which are essential for carcinogenesis, are unclear. Suppressor genes normally suppress the tumorigenic phenotype by keeping the growth of cells in check; it is their inactivation that contributes to malignant transformation. Development of colon cancer appears to take place by stepwise accumulation of multiple genetic alterations during the progression from normal colon to adenoma and carcinoma. Activation of ras, an early event in this sequence, is found in 50% of colon cancers; overexpression of c-myc is found in approximately 80%. Inactivation of suppressor genes, which occurs during later stages, is noted in greater than 70% of tumors. A current model of colonic tumorigenesis is presented. PMID- 2229992 TI - Can the blood urea nitrogen/creatinine ratio distinguish upper from lower gastrointestinal bleeding? AB - We wanted to know if the blood urea nitrogen to creatinine (BUN/Cr) ratio could help distinguish upper from lower gastrointestinal bleeding. We analyzed retrospectively patients admitted to our hospital for gastrointestinal bleeding over the past 5 years. A total of 126 patients represented 74 upper bleeds and 52 lower bleeds. The mean BUN/Cr ratio was significantly higher in upper than lower bleeders, 34.8 and 17.8 respectively (p less than 0.001). No lower bleeder had a ratio of greater than or equal to 36, whereas 38% of upper bleeders had a ratio of greater than or equal to 36. The BUN/Cr ratio may be an easy, cheap method of distinguishing upper from lower gastrointestinal bleeding in some cases. A BUN/Cr ratio of greater than or equal to 36 suggests upper gastrointestinal bleeding, whereas a ratio of less than 36 is not helpful in locating the source of bleeding. PMID- 2229993 TI - Stasis syndromes following gastric surgery: clinical and motility features of 60 symptomatic patients. AB - We retrospectively reviewed the records of 60 patients who had been referred for gastrointestinal manometry because of stasis after gastric surgery. Nausea, vomiting, bloating, abdominal pain, and weight loss were the most common symptoms. Two thirds of these patients had a well-documented history of peptic ulcer before their initial operations; in others, surgery was performed for other reasons, such as obesity (5%) or reflux esophagitis (8%). Twelve patients had undergone truncal vagotomy and a "drainage operation" and 48 had received a partial gastrectomy with a gastroenterostomy: Billroth I (n = 8), Billroth II (n = 11), Roux-en-Y (n = 29). All patients had recordings of gastrointestinal manometry; 16 also had a scintigraphic measurement of gastric emptying. Measurements were compared with data from healthy controls. Gastric manometry, which could be assessed only in the group with an intact antrum, was characterized by antral hypomotility (p less than 0.05). Gastric emptying studies showed rapid early emptying of liquids and delayed emptying of solids (both p less than 0.05). In the whole group, fasting jejunal motility was characterized by absence of phase II in 13, presence of bursts of phasic activity in 18, and abnormal propagation of phase III in 8. A significantly increased frequency of phase III of MMC was noted in the patients after Billroth II and Roux-en-Y operations. Postprandially, 19 patients failed to develop a "fed pattern."(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229994 TI - Limitations in the evaluation of therapy in inflammatory bowel disease: suggestions for future research. AB - The current treatment of inflammatory bowel disease (IBD), though improved over earlier therapies, remains variable rather than consistent and supportive rather than curative. The similar management of ulcerative colitis (UC) and Crohn's disease (CD), which are thought to be differing though related disorders, suggests that therapy is nonspecific. The variation in therapeutic practices results from the fact that the etiologies of the diseases are obscure, from limited knowledge of the biological and pharmacological actions of drugs commonly prescribed (sulfasalazine, 5-ASA compounds, steroids, 6-MP and azathioprine), from an inadequate understanding of genetic differences influencing drug metabolism, from insufficient awareness of the factors influencing drug efficiency (concurrent use of antimotility drugs, cigarette smoking, food combinations), from the variability of the patient groups studied (extent and severity of disease), and from incomplete documentation of the clinical status of patients at the time of therapeutic trial. Future advances in treatment will depend on gaining new information about the nature of IBD and of drug pharmacology and bioavailability, derived from collaborative studies by clinicians, clinical investigators, and basic scientists. Important areas for IBD research include the biology of intestinal epithelium, the nature of the IBD inflammatory reaction and of gut mucosal immune regulation (via the application of new biotechnologies) and more representative experimental animal models. Decisive multicenter therapeutic studies require agreement on definitions of ulcerative colitis and Crohn's disease, accurate characterization of patient groups, acceptable objective criteria of IBD severity and activity, and reliable indicators of therapeutic response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2229995 TI - Frequency of recovery of Blastocystis hominis in clinical practice. AB - We examined the frequency of isolation of Blastocystis hominis from stools of patients seen in an indigent-care teaching hospital. Over a 2-year period, 2,744 stool specimens were examined prospectively. B. hominis was found in 262 stools (9.5% of all stool specimens and 53.5% of the positive specimens). Clinical data were obtained from 80 patients with stools positive for B. hominis. B. hominis was the only parasite isolated in 39 of 47 (83%) of the adults, compared with 17 of 33 (52%) of the children (p = 0.006). All but 2 of 52 patients without concomitant parasitic infection or bacterial pathogens in stool had gastrointestinal symptoms (41 abdominal pain, 26 diarrhea, and 5 vomiting), but no association was seen with fever, peripheral leukocytosis, stool occult blood, fecal leukocytes, or endoscopic or radiologic evidence of colitis. Therefore, B. hominis was frequently recovered from stools examined in a hospital clinical parasitology laboratory. The clinical presentations of patients in our series did not suggest that B. hominis was invasive. Most patients with B. hominis probably do not require treatment since they will either have spontaneous resolution of symptoms or will be found to have an alternative explanation for their problem. PMID- 2229996 TI - Clinical significance of cholelithiasis in patients with decompensated cirrhosis. AB - There is general agreement that the prevalence of gallstones in cirrhotics is high (at least twice that in the general population), but the pathogenetic link between cirrhosis and cholelithiasis is still uncertain. The influence of cholelithiasis on survival in cirrhotics is also unknown. During an 8-year period, we observed 90 patients affected by decompensated cirrhosis: 36 of them (40%) turned out by cholecystographic/cholangiographic or ultrasonographic examination to have cholelithiasis. We were not able to demonstrate any correlation between cholelithiasis and sex, age of patients, etiology of cirrhosis, severity of the illness, degree of portal hypertension, previous gastrointestinal bleeding, number of pregnancies, or levels of serum cholesterol, bilirubin, and triglycerides. During the follow-up observation, (range, 1-91 months), 30 patients died. Survival curves analyzed by the log-rank test did not show any difference between patients with or without gallstones. We therefore confirm that cirrhosis is a lithogenic condition, but we were not able to explain the reasons for the close relationship between cholelithiasis and cirrhosis. Gallstones, however, did not affect the survival of these patients. PMID- 2229997 TI - Risk factors for gallstones among Chinese in Taiwan. A community sonographic survey. AB - A health survey of adults aged 30 years or more was carried out in southwest Taiwan to determine the prevalence of gallstones and to study risk factors associated with gallstones. Blood samples were collected and abdominal sonographic examination and anthropometric measurements were performed on a total of 923 people. The 40 gallstone cases detected resulted in a prevalence of 4.3%. The risk factors explored included age, sex, hepatitis, obesity, hyperlipidemia, and diabetes mellitus (DM). Age and DM were the only significant factors associated with gallstones in our study. With a reference group of 30-39-year olds as a comparison, multiple logistic regression analysis showed a trend effect with odds ratios of 1.73, 3.74, and 6.32 for age groups of 40-49, 50-59, and 60 or above, respectively. The odds ratio for DM was as high as 2.59. However, sex, body weight index, chronic hepatitis B, and hyperlipidemia were not significantly associated with gallstones. PMID- 2229998 TI - Gallstone disease in north India: clinical and ultrasound profile in a referral hospital. AB - We studied the prevalence of gallstones in patients with upper abdominal pain, heaviness, or discomfort by ultrasound examination of the gallbladder. The actual ultrasound examination was performed by a clinical gastroenterologist blinded to the symptoms. Of 1,680 consecutive dyspeptic patients, 500 (29.8%) had gallstones. The gallbladder was contracted in 450 (91.2%), normal-size in 36 (7.2%), and distended in 8 (1.6%). Biliary colic was more frequently the presenting complaint in patients with a contracted gallbladder than in those with normal size gallbladder (p less than 0.001). Dyspepsia was more frequent in the presence of a normal size gallbladder than a contracted one (p less than 0.001). We conclude that ultrasonography of the gallbladder by the clinician has a high diagnostic yield, and the symptom complex has an excellent correlation with the sonographic appearance. PMID- 2229999 TI - Small bile duct abnormalities in sarcoidosis. AB - We report four patients with hepatic involvement of sarcoidosis manifested primarily by bile duct depletion. The patients developed fever, weight loss, anorexia, a markedly elevated alkaline phosphatase, and mildly abnormal serum levels of aspartate aminotransferase. Endoscopic retrograde cholangiopancreatography showed slight intrahepatic irregularities but were not diagnostic of sclerosing cholangitis. Liver biopsy showed predominantly bile duct depletion, ranging from an estimated 10-100% absence of bile ducts in portal areas, which correlated with the degree of fibrosis. The degree of bile duct depletion is useful as a histological marker in patients with sarcoid liver disease. Steroids improve symptoms, but do not inhibit the development of "ductopenia." PMID- 2230000 TI - Spontaneous reactivation in chronic hepatitis B: patterns and natural history. AB - We identified spontaneous reactivation of hepatitis B virus (HBV) retrospectively by utilizing serum alanine aminotransferase and HBV DNA in 19 men (79% homosexual), with an estimated annual incidence of 7.3%. In 11 patients, spontaneous reactivation occurred as a single episode and in eight patients, reactivation was recurrent, with two to five episodes each. The mean serum alanine aminotransferase level was elevated over 10-fold at the peak of reactivation. Serum anti-HBc IgM was detected during 73% of the reactivation episodes. Actuarial analysis revealed that reactivation was long lasting with 45% and nearly 20% of episodes continued after 6 and 24 months, respectively. The course of 24 chronic HBV carriers with a negative serum HBV DNA test and normal alanine aminotransferase levels at initial appearance was unremarkable. We could not identify clinical features predictive of reactivation or its resolution. Severe reactivation hepatitis occurred in three patients (10%), with two deaths (6%). None of the patients lost HBsAg. Spontaneous reactivation in chronic hepatitis B can appear variably, persist long term, recur, and be fatal. Therefore, accurate classification of chronic HBV infection requires prolonged observation, and spontaneous reactivation should be considered a variable in therapeutic trials for chronic hepatitis B. PMID- 2230001 TI - Mallory-Weiss syndrome after cardiopulmonary resuscitation. AB - We report hematemesis from Mallory-Weiss tears after successful cardiopulmonary resuscitation (CPR). A computer search of the English language literature disclosed only 3 similar cases, and we review them. This complication of CPR may occur more frequently than recognized and should be prevented by careful technique. PMID- 2230002 TI - A nongastrin malignant ampullary tumor causing gastric acid and pepsin hypersecretion. A case report. AB - We report a case of multiple duodenal ulcers with gastric hypersecretion due to a nongastrin secretagogue produced by a malignant tumor of the pancreas in a 78 year-old man. The case resembled a Zollinger-Ellison syndrome (ZES) with high acid output (basal acid output 27, sham meal-stimulated 37, maximum acid output 47 mEq/h), but with fasting gastrin 43 pg/ml, nonresponsive to secretin. As in ZES, pepsin output was comparatively low, and secretion was inhibitable by atropine (50% inhibited by 1 microM). The tumor removed at surgery contained less than 1 ng gastrin per gram, but was many times more potent than pentagastrin in stimulating acid from a lumen-perfused rat stomach. The tumor also contained cholecystokinin (CCK-8 and CCK-33), motilin, insulin, and somatostatin, which were also present in adjacent normal pancreas; in addition, the tumor contained pancreatic polypeptide and pancreatic cancer-associated antigen. This case represents a rare syndrome due to an as yet undefined peptide secreted by a (frequently malignant) pancreatic endocrine tumor and masquerading as ZES. This is the first report of studies of pepsin secretion and of the effect of atropine, suggesting that the physiologic effects of the secretagogue resemble that of gastrin. PMID- 2230003 TI - Chylous ascites should suggest constrictive pericarditis even in a patient with cirrhosis. AB - Chylous ascites, a milky, high triglyceride fluid is usually found in patients with lymphatic obstruction from malignancy. We describe a patient with cirrhosis who developed constrictive pericarditis and chylous ascites. Long-standing portal hypertension compounded by elevated central venous pressure provided several pathophysiologic contributions to the formation of the chylous ascites. Chylous ascites even in a cirrhotic requires prompt assessment for conditions leading to elevated central venous pressure. PMID- 2230004 TI - Morphological study of cholesterol hepatolithiasis. Report of three cases. AB - Three cases of pure cholesterol intrahepatic stones are compared morphologically to those of calcium bilirubinate stones. Cholesterol stones were found in the intrahepatic bile duct of the left lateral lobe in two cases and in both the left lateral and the right posterior lobe in one. Although the chronic inflammatory reaction and fibrous thickening of bile duct wall were similar in both types of hepatolithiasis, the proliferation of intrahepatic periductal glands and the production of mucin were rather mild, compared to that is the liner containing calcium bilirubinate stones. Multiple intramural cholesterol calculi and cholesterin granulomas (cholesterin crystals surrounded by foreign-body giant cells) were found within the cystically dilated small bile duct branches and/or conduits of periductal glands. The calculi and granulomas were characteristic for cholesterol hepatolithiasis. These findings suggest that the formation of the cholesterol stones differs from that of calcium bilirubinate stones; the perturbation of factors influencing cholesterol nucleation in the hepatic bile may be related to the changed microenvironment of the intrahepatic bile ducts, which is followed by the formation of cholesterol stones. PMID- 2230005 TI - Ultrasound-Doppler diagnosis of Budd-Chiari syndrome. AB - We report a case of apparently idiopathic Budd-Chiari syndrome, diagnosed by ultrasound and Doppler sonography, in a patient with latent myeloproliferative disease. This case proves that Doppler sonography shows in the hepatic veins a flow pattern suggestive of partial thrombotic obstruction. Moreover, we suggest that the search for a latent myeloproliferative disorder, by means of the spontaneous erythroid colonies formation in culture of bone marrow or blood mononuclear cells, should be routinely included in the diagnostic evaluation of each case of hepatic vein thrombosis without other recognizable causes. PMID- 2230006 TI - Portal venous gas in a patient with Crohn's disease. AB - Portal venous gas usually occurs in the setting of an acute abdomen. Several causes for benign portal venous gas (PVG) have been reported. We describe the finding of PVG by computed tomography in a febrile patient with Crohn's disease and discuss the clinical implications of such a finding. PMID- 2230007 TI - Iliocaval vein thrombosis as a presentation of Crohn's disease. PMID- 2230008 TI - Small bowel obstruction due to simultaneous volvulus and intrahernial incarceration of a carcinoid tumor. PMID- 2230009 TI - DNA ploidy of tumor cells and clinical outcome of colorectal cancer patients. PMID- 2230010 TI - Propranolol and metronidazole for the treatment of metronidazole-resistant giardiasis. PMID- 2230011 TI - Toxic megacolon (TM) due to Salmonella. PMID- 2230012 TI - Postoperative portal vein obstruction in patients with idiopathic portal hypertension. PMID- 2230013 TI - Development of a methodology for malariogenic stratification as a tool for malaria control. AB - Modified plan of operation (MPO) for malaria control launched in 1977 failed to curb malaria incidence beyond about 2 million cases per annum and thus necessitated development of multipronged malaria control strategies based upon malariogenic stratification. A model for such stratification based upon six most sensitive, but quantifiable, epidemiological parameters for which records are easily available at PHC level, namely, topography, average annual rainfall, vector(s), average annual parasite incidence (API) for the last five years, epidemic potential and vulnerability was developed. This model has been successfully tried in the State of Karnataka and on that basis the whole State has been divided into five strata in order of increasing endemicity. Objectives of malaria control for each of the stratum so defined have been proposed. PMID- 2230014 TI - Malaria as anthropo-ecosystem (MAES): Part V. Self-regulation and stability of MAES. AB - In biological ecosystems, population tends to fluctuate above or below asymptotic level or the 'carrying capacity'. Self-regulation is achieved by extrinsic, that is, environmental limiting factors and intrinsic, that is, physiological and genetic factors. In Malaria Anthropo-Ecosystem (MAES) which is much more intricate and complex system, Plasmodium being endoparasite is required not only to interact with intrinsic factors of its vertebrate and invertebrate host but also to regulate itself to environmental factors to which its both the hosts are subjected. Attempt has been made to provide, on the basis of present knowledge, the probable explanation of self-regulatory mechanisms from molecular, cell, organ/organism, population/community levels of vertebrate and invertebrate hosts which give stability to MAES as a whole system. PMID- 2230015 TI - Epidemiological study of measles in Singur, West Bengal. AB - A measles survey in 10 villages of Rural Health Unit and Training Centre, Singur revealed 581 cases of measles from January to June 1986. The overall attack rate was 40/1000. The highest attack rate (43.5 per cent) was observed in the age group of 1-2 years followed by 6-8 months age group. 11.5 per cent of the cases were below the age of 9 months and 10.4 per cent cases were above the age of 15 years. 42.3 per cent of cases developed one or the other complications. Diarrhoea and respiratory infections were the two common complications. Case fatality rate was only 0.17 per cent. Epidemiological aspects of these observations are discussed. PMID- 2230016 TI - Seroepidemiology of hepatitis B in Nepal. AB - To assess the prevalence of BHV infection in Nepal sera of 2,555 healthy individuals of different age groups from different parts of the country were examined for the markers of the infection. BHsAg and anti-HBs were assayed by R PHA and PHA methods respectively and anti-HBc by ETA method. Anti-HBc was positive in 43.5 per cent of 2,555 sera of healthy individuals in Nepal. HBsAg was in 0.9 per cent (1.5 per cent in male and 0.5 per cent in female) and anti HBs in 7.7 per cent (7 per cent in male and 8 per cent in female). The prevalence of HBsAg and anti-HBs was higher in urban than in rural areas, and the highest prevalence of these markers was noted in health care personnels (HBsAg 2.6 per cent and anti-HBs 17 per cent). HBsAg was not detectable in infants and young children, and the highest prevalence rate was observed in 6 to 15 years age group. The main mode of spread of HBV infection in Nepal was the horizontal transmission in pre-adolescent and adolescent children. HBV infection is common in Nepal but the BHsAg carrier rate is much lower than reported from other Asian countries. PMID- 2230017 TI - Detection of HBsAg in newborns. AB - Cord blood samples collected from 150 newborns were tested for HBsAg using micro ELISA technique. Only 8 (5.3 per cent) out of 150 samples were found to be positive for HBsAg in variable titres. It is important to identify these HBsAg positive newborns so that appropriate measures could be adopted at the earliest to prevent the complications of HBsAg carriage. PMID- 2230018 TI - Cholera outbreak in Delhi--1988. AB - Delhi experienced an outbreak of cholera during July-August 1988 which affected residents from all walks of life. A total of 1824 laboratory confirmed cholera cases were detected in two months period at I.D. Hospital, Delhi alone. The number of cholera cases in July-August 1988 was 5-10 times that of the same period during the previous years in the Capital. The outbreak was caused by Vibrio cholerae Ogawa biotype ElTor. Majority of the laboratory confirmed cases (about 74 per cent) were seen in children under the age of 15 years. Though the cases were spread all over Delhi, almost three-fourths of total cases were reported from two specific zones (Shahdara and Civil Lines). Most of the isolates were sensitive to all antibiotics tested. The proportion of isolates resistant to furazolidone during this outbreak was substantially higher than in previous years suggesting that the outbreak may have been caused by the introduction of a new strain rather than proliferation of endemic strain. The salient features of the outbreak are discussed. PMID- 2230019 TI - Occurrence of salmonellae in slaughtered pigs, goat meat, meat handlers and slaughtered-house workers. AB - Of 413 samples comprising 200 goat meat, 100 pig's faeces, 50 faeces of slaughtered-house workers, 13 faeces and 50 nailwashings of goat meat handlers collected from different shops of Calcutta Corporation, 25 (6.05 per cent) yielded 13 serotypes of salmonellae. The commonest serotypes was S. newport (24 per cent), followed by S. enteritidis (12 per cent), S. anatum (12 per cent) and S. typhimurium. Isolation rate of salmonellae was 12 (6 per cent) from goat meat, 10 (10 per cent) in pig's faeces and 3 (6 per cent) in nailwashings. S. newport (50 per cent) in goat meat and S. anatum (30 per cent) in faecal contents of pigs were the predominant serotypes. None of the faecal samples of goat meat handlers and slaughtered-house workers yielded salmonellae. PMID- 2230020 TI - Diarrhoeal diseases in children--a survey in east Godavari District of Andhra Pradesh. AB - A survey carried out in East Godavari District of Andhra Pradesh to determine the extent of diarrhoeal disease problem in children under five years of age revealed an incidence of 7.5 per cent. It was two times more frequent in infants than in the age group of 1-4 years. Mortality due to diarrhoea was 1.1 per thousand children which was two times more in infants than in the age group of 1-4 years. As high as 68.5 per cent of children were treated with antibiotics. There is a need to standardize management of diarrhoeal diseases in order to eliminate wasteful use of antibiotics. PMID- 2230021 TI - Action of metronidazole on Entamoeba histolytica: an ultrastructural study. AB - Metronidazole (19 micrograms/ml) caused progressive increase in vacuolization in Entamoeba histolytica cells with disintegration of its plasma membrane leading to almost complete disappearance of the latter within 3 hours. The drug also induced formation of helical ribosomal aggregates in the cytoplasm and disappearance of button like structures inside the nucleus. PMID- 2230022 TI - Enzyme linked immunosorbent assay for the diagnosis of human neurocysticercosis: a preliminary report. AB - The diagnostic efficacy of an indirect enzyme linked immunosorbent assay (ELISA) was evaluated in cases of neurocystecercosis. Subjects studied included 22 cases and 30 controls (comprising 12 cases of surgically confirmed hydatid disease, 5 cases each of tuberculoma and P.U.O. and 8 cases of pyogenic meningitis). A standard ELISA was performed using porcine cysticerci as antigen. Sensitivity and specificity of the test were calculated for serum and cerebrospinal fluid separately. The test was found to give a sensitivity of 68 and 33 per cent for serum and C.S.F. respectively. The specificity for confirmed case was found to be cent per cent for both with the criteria of reporting used. The sensitivity of the test may be increased by using purified specific antigen and/or sandwich ELISA instead of indirect ELISA technique. PMID- 2230023 TI - Biometrical variations in haematophagous arthropods. II. DV/D ratio of male terminalia of wild Culex quinquefasciatus SAY (Diptera: Culicidae) in India. AB - The DV/D ratio of male terminalia is considered as most reliable morphometric feature to distinguish Culex pipiens from Cx. quinquefasciatus. In India although only Cx. quinquefasciatus is known both in the filariasis (Bancroftian) endemic and non-endemic areas, there has been no study on the amounts of morphometric variation among wild strains of this species. This paper reports variation in the DV/D ratio of Cx. quinquefasciatus collected from 7 localities of Delhi (D), Lucknow (L), Patna (P), Varanasi (V), Rajahmundry (R), Jabua (J) and Alleppey (A) between June and October 1986. The mean value of DV/D ratio in all the strains varied from 0.78 to 0.99 with overall mean of 0.89. The range of the ratios was 0.30 to 1.88. There were 1.28 per cent specimens (9 out of 700) with ratio below 0.50 and the rest 98.72 per cent with ratio 0.50 and above. The DV/D ratio of 0.50 should therefore be accepted as lower limit for Cx. quinquefasciatus instead of the earlier established value of 0.40. The coefficient of variation (CV) among the 7 strains indicates the following progression of variability in the DV/D ratio from most stable to most variable strain: L greater than V greater than R greater than A greater than J greater than P greater than D. The range of mean CV values in different strains was very close with most stable L strain 19.19 and most variable D strain 25.92. The amounts of variation, as estimated by coefficient of variation, were found to be significantly different between the following strains: Delhi and Lucknow (P less than 0.01 at 198 df), Lucknow and Patna (P less than 0.05 at 198 df), and Delhi and Varanasi (P less than 0.05 at 198 df).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230024 TI - Blood meal analysis of Phlebotomus argentipes in eight districts of West Bengal. AB - Eight districts of West Bengal (India) were surveyed for the biting habit of Phlebotomus argentipes using agar gel diffusion method. Blood meal indices were found different in the two biotopes, human dwellings and cowsheds. A total of 395 blood meals were analyzed. The blood meal indices in the human dwellings were human 68.8 per cent, cow 38.9 per cent, both human and cow 10.2 per cent, others 2.5 per cent and in the cowsheds: human 19.7 per cent, cow 91.6 per cent, human and cow 13.9 per cent and others 2.5 per cent. These indicated that P. argentipes did not show preference to any blood meal. PMID- 2230025 TI - Magnitude of DDT resistance in Anopheles culicifacies in Maharashtra State. PMID- 2230026 TI - Effective pretreatment by cysteine proteinase inhibitor for improved analysis of protein components of trematodes on SDS-PAGE. AB - Since Fasciola sp. contained proteolytic enzyme(s), it was confirmed that degradation took place in protein components in extracts of the liver flukes, which resulted in lack of clarity of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Degradation was shown to occur mostly during a heating process of the extract samples. The proteolytic activity in the extracts was completely blocked and electrophoretic patterns were improved only by the use of cysteine proteinase inhibitor N-[N-(L-3-trans-carboxyoxiran-2-carbonyl)-L leucyl]-agmatine (E-64). Great improvement was also noted in electrophoretic patterns of the extracts of other trematodes, such as Paragonimus westermani, P. miyazakii and Clonorchis sinesis, when their extracts were treated with E-64. PMID- 2230028 TI - On the morphology and life-history of Hemiurus luehei Odhner, 1905 (Digenea: Hemiuridae). AB - Previously undescribed cystophorous cercariae which develop in sporocyst germinal sacs in the tectibranch opisthobranch Philine denticulata (Adams) are shown to be cercariae of Hemiurus luehei Odhner, 1905 (Hemiuridae), a common stomach parasite of clupeid and salmonid fishes off the Atlantic coast of Europe, in the Baltic and the Mediterranean Sea. The free-swimming cercariae are seized by calanoid copepods. Temora longicornis (Muller) and Acartia tonsa Dana acted as suitable experimental intermediate hosts. Pressure by the copepod mouth appendages causes delivery tube eversion and the injection of the cercarcial body into the haemocoel. Sagitta sp. was found naturally infected with a metacercaria of H. luehei. The cystophorous cercaria and metacercaria are described using light and scanning electron microscopy. Adults from herring were examined under the stereoscan electron microscope. PMID- 2230027 TI - Scanning and transmission electron microscopy of the female reproductive system of Schistosoma margrebowiei Le Roux, 1933. AB - Transmission electron microscopy shows that the uterus of female Schistosoma margrebowiei possesses the same ultrastructure as that of the tegument but lacks spines and sense organs. It does not possess secretory cells and opens at the gonopore which by scanning electron microscopy was seen to be composed of numerous leaf-like protrusions. The morphology of the ovary is comparable with that of other Digenea. Immature and mature ova possess cortically arranged granules and occur within the posterior zone of the ovary. Cilia and lamellae line the luminal surface of the oviduct and ootype, the lamellae running unidirectionally along the duct. Only a single type of secretory cell is seen within Mehlis' gland and this produces dense bodies which are associated with Goldi bodies. Narrow cytoplasmic channels supported by microtubules deliver these secretory bodies to the ootype. The vitelline duct is lined with cilia and lamellae and the vitelline gland contains four types of cells, S1, S2, S3 and S4. Calcareous corpuscles are found within mature S4 cells. PMID- 2230029 TI - Effects of 5-hydroxytryptamine (serotonin) on the incorporation of 32P-inorganic phosphate into phospholipids in Hymenolepis diminuta (Cestoda). AB - 5-Hydroxytryptamine (5-HT) (1,2 and 5 mM) significantly stimulated the incorporation of radioactive inorganic phosphate (32Pi) into phosphatidylinositol, phosphatidylethanolamine, phosphatidic acid and also total phospholipid fraction of Hymenolepis diminuta after one hour of incubation. Such effect was both time and concentration dependent. In the presence of 5-HT early labelling of phosphatidylinositol was observed. Also, the percentage stimulation by 5-HT was the highest in this fraction under all experimental conditions. The inorganic, organic, total and phosphatidylcholine-bound phosphate of H. diminuta incubated with 5-HT were not significantly different from those of the control under all incubation conditions. Results reported herein suggest that messenger molecules that are derived from phosphoinositides may be involved in the stimulatory mechanism of 5-HT in H. diminuta. PMID- 2230030 TI - Epidemiology of hydatid disease in Sardinia: a study of fertility of cysts in sheep. AB - Hydatidosis, caused by Echinococcus granulosus, is a cyclozoonotic disease of economic significance in Sardinia. The life-cycle involves stray and sheep dogs as definitive hosts and sheep, pigs, goats and cattle as intermediate hosts. The most important intermediate host is sheep, due to home slaughtering with ready access of the viscera to dogs. This survey was undertaken in 1987 to ascertain the epidemiological significance of sheep in maintaining the life-cycle. A total of 700 (91.3%) of 767 sheep harboured hydatid cysts. The frequency distribution of the number of hydatid cysts was over-dispersed. Of 497 infected sheep, 7.6% had fertile cysts, 75.7% sterile cysts and 16.7% fertile + sterile cysts. PMID- 2230032 TI - The pig as an intermediate host for Taiwan Taenia infection. AB - Eggs (1000-100,000/animal) of Taiwan Taenia were inoculated per os into 14 Small Ear-Miniature (SEM), 19 Landrace-Small-Ear-Miniature (L-SEM), and 5 Duroc Yorkshire-Landrace (DYL) pigs. These animals were sacrificed 7-107 days after infection. Thirty-four pigs were found to be infected with Taiwan Taenia cysticerci and the infection rates of SEM, L-SEM, and DYL were 86%, 89% and 100% respectively. The cysticerci recovery rates of SEM, L-SEM and DYL pigs were 27.2%, 1.7% and 0.27% respectively. Cysticerci were recovered only from the livers and none were found in muscles, viscera or other parts of the carcasses. More cysticerci were located in the liver parenchyma (71%) than on the liver surface (29%). Taiwan Taenia cysticerci were smaller than those of classical T. saginata or T. solium. Moreover, Taiwan Taenia cysticerci had 2 rows of rudimentary hooklets on the scolex. The results of this study indicate that young pigs are good intermediate hosts for Taiwan Taenia and that the SEM pig is a satisfactory host for experimental studies with this tapeworm. These results were similar to other studies with different geographic strains of the T. saginata like tapeworm in the Far East. These strains appear to be the same and possibly a new species. PMID- 2230031 TI - Establishment, development and fecundity of Taenia crassiceps in the intestine of prednisolone-treated Mongolian gerbils and inbred mice. AB - Worm establishment, development and fecundity of Taenia crassiceps in the intestine of prednisolone (PTBA)-treated, 15- and 4-week-old Mongolian gerbils and 9-week-old inbred mice of 4 strains (AKR/J, BALB/cAn, B10D2/oSn and C57BL/KsJ) were investigated following oral administration of metacestodes. Gerbils were divided into 5 groups of 4 animals each according to the host age and commencement day of PTBA-treatment (day -13, -7 or 0 relative to infection). Worm recovery from the intestine on day 35 postinfection was not affected by host age, but fewer worms were recovered the earlier the commencement of PTBA treatment. Worm size, determined by wet weight, total length and proglottis number, correlated inversely with worm burden, suggesting they were affected by the crowding effect. Proglottides were released normally in the faeces but were markedly depressed in all groups except for that of young gerbils. Furthermore, egg production and its development in gravid proglottides were markedly depressed in all groups. In PTBA-treated mice of 4 strains, sexually mature but not gravid worms were recovered from all mice of the AKR/J strain on days 20-32 postinfection, but none or few worms from the intestine of the others. PTBA treatment did not inhibit all protective host defence mechanism(s) in the unnatural or alternative rodent definitive host of T. crassiceps. PMID- 2230033 TI - Comparative susceptibility to anthelmintics of Brugia pahangi in jirds infected by different methods. AB - It is possible to infect jirds with Brugia pahangi by three methods. Infective larvae (L3) can be injected either intraperitoneally (ip), when adults develop in the peritoneal cavity, or sub-cutaneously (sc), when they develop in the lymphatics or the heart and blood vessels associated with the lungs. Alternatively adult worms which have been grown in the peritoneal cavities of jirds can be implanted into the peritoneal cavities of other jirds. This latter system has been widely used for screening for new filaricides. We have compared the activity of 9 macrofilaricidal compounds against these 3 types of infection. Mebendazole and albendazole were more active against implanted adults than against L3 induced adults in the peritoneal cavity. Oxibendazole, flubendazole, CGP24588A and oxfendazole were equally active against both types of worm. CGP20376, Mel Ga and Mel Ni were more active against adult worms derived from inoculated L3 than implanted worms. When comparing intra-lymphatic and ip adults (both derived from L3 infections and in the same jirds) albendazole and CGP20376 were active at the same levels against both types of infection. Mebendazole, flubendazole, oxfendazole, CGP24588A, Mel Ga and Mel Ni were more active against ip adults than intra-lymphatic adults. No drug was more active against intra lymphatic adults than against adults. PMID- 2230034 TI - Effects of infection with Angiostrongylus cantonensis on the circulating haemocyte population and the haematopoietic organ of the host snail M-line Biomphalaria glabrata. AB - The number of circulating haemocytes, the size of the haematopoietic organ, and the size of haemocyte capsules around the parasite were studied in M-line Biomphalaria glabrata snails exposed to 100 or 400 first-stage larvae of Angiostrongylus cantonensis. The number of haemocytes in exposed snails increased significantly at 1 day post-exposure, decreased to control value, and then increased again. The decrease in number of circulating haemocytes is probably due to the removal of cells from the circulation to participate in encapsulation of larvae. The majority of circulating haemocytes in M-line B. glabrata are fully spread granulocytes, which increase significantly in number in snails following exposure to A. cantonensis larvae. However, populations of partially-spread granulocytes, round cells, hyalinocytes and miscellaneous haemocytes were relatively constant. The size of capsules around the parasite increased during the 42-day interval of the experiment. The haematopoietic organ increased in size in response to infection. PMID- 2230035 TI - Characterization of glucose uptake by Trichuris globulosa (Nematoda) in vitro. AB - 14C-glucose uptake by adult Trichuris globulosa is found to be a non-linear function of time and limiting substrate concentration. The uptake is a two component process, an initial rapid burst is followed by a lower steady state, implying a mediated process. The uptake is dependent on Na+ ions which cannot be replaced by K+, Li+ or choline. The uptake is also dependent on pH, being maximal at pH 7.4. 14C-glucose absorption is markedly inhibited by glucose, phlorizin, ouabain and to a smaller extent by a number of monosaccharides and other sugar phosphates, nucleosides and metabolic inhibitors like p-nitrophenyl phosphate and iodoacetate. The inhibition constant for glucose, phlorizin and ouabain has been found to be 8 mM, 5 mM and 7 mM, respectively. A modified Dixon-plot shows that glucose is a completely competitive inhibitor for 14C-glucose uptake while the nature of competitive inhibition of phlorizin and ouabain are found to be partial. PMID- 2230036 TI - Scanning electron microscopy of the cuticular armature of the nematode Gnathostoma spinigerum Owen, 1836 from cats in Laos. AB - The body surface of an immature female Gnathostoma spinigerum found for the first time in the definitive host (Felis catus f. domestica) in Laos was studied using a scanning electron microscope. All types of cuticular spines, which are one of the most important features for species identification of gnathostomid nematodes, together with their spatial arrangement, are described and figured. PMID- 2230037 TI - Seasonal variations in the populations of infective larvae on pasture and the numbers of nematode eggs in the faeces of farmed goats. AB - The levels of nematode egg production in goats and the availability of infective larvae (L3) on pasture were investigated on a dairy unit in New South Wales, Australia. The output of eggs by adult goats was always above 300 epg. The profile of the graph of larval availability in herbage paralleled those for temperature and rainfall, suggesting that larval peaks occurred when the temperature and availability of moisture were optimal. The dominant genus was Trichostrongylus, followed by Haemonchus, then Ostertagia. A larger proportion of Haemonchus larvae in the cultures of faeces were collected during the summer months. PMID- 2230038 TI - Abstracts of the 25th meeting of the European Association for the Study of the Liver. Budapest, Hungary, 3-6 October, 1990. PMID- 2230039 TI - Surveillance of the surgical wound. PMID- 2230040 TI - Comprehensive surveillance of surgical wound infections in outpatient and inpatient surgery. AB - A surgeon-specific computer-generated monthly questionnaire was used to improve surveillance of surgical wound infections in outpatients as well as inpatients following discharge. From July 1988 through June 1989, 20,536 surgical procedures were performed at our medical center, of which 53% were for outpatients. The total wound infection rate was 0.63%: 0.13% in outpatients and 1.2% in inpatients (p less than .005). Of the infected wounds, 20% were reported by the survey alone and would have gone undetected by conventional surveillance methods (71.4% of outpatient and 13.8% of inpatient wound infections). As a whole, clean and clean contaminated wounds in outpatients were much less likely to become infected than those in inpatients. Wound cultures were not obtained in 85% of infections reported by the survey alone, and were less likely to be obtained in outpatients. The average time spent by the infection control department on the survey was approximately two hours per week. PMID- 2230041 TI - Variation in risk for falls by clinical department: implications for prevention. AB - To examine rates of falls and injuries by clinical department, a retrospective analysis was performed of 874 inpatient falls during a one-year period in a 1,000 bed acute-care hospital. Incident reports were reviewed, and for those patients injured, medical records were abstracted. Fall rates were calculated by age, sex and service using total patient days as the denominator. During 1983, 874 falls occurred during 282,713 adult patient days (31/10(4) days). Fall rates were significantly higher (odds ratio = 2.12; 95% confidence interval [CI]: 1.84, 2.45) in the neuroscience and psychiatry departments (53/10(4) days) compared with other adult services combined (25/10(4) days); this difference persisted after direct adjustment for age. Differences by clinical department persisted throughout four additional years of surveillance, although fall rates for the oncology service increased. Injuries following falls occurred among 200 (22.8%) patients. These data indicate that falls are not random events, and that falls and injury prevention programs can be more appropriately focused by consideration of clinical department. PMID- 2230042 TI - Plasmid DNA fingerprinting of Acinetobacter calcoaceticus subspecies anitratus from intubated and mechanically ventilated patients. AB - Forty-three intubated and mechanically ventilated patients in five intensive care units (ICUs) of one hospital developed respiratory colonization or infection with Acinetobacter calcoaceticus subspecies anitratus over a 16-month interval. Neither the frequency nor rate of A anitratus isolation exceeded the hospital endemic norms. Single isolates from 34 of the patients were subtyped by plasmid DNA analysis, two biotyping systems and antimicrobial susceptibility to 24 drugs. Plasmid DNA fingerprints were distinct in 18 isolates (they differed from each other and all others), similar in two and identical or similar in ten. The latter group of isolates were recovered from patients in four ICUs. Reproducibility of biotyping was poor. Neither biotyping nor antimicrobial susceptibility were successful in identifying sameness among the group isolates nor differences among other isolates. We conclude that plasmid DNA fingerprinting should be used to assess the possibility of multiple patient transmissions of the same A anitratus strain in the absence of an obvious outbreak. PMID- 2230043 TI - Achromobacter xylosoxidans bacteremia. PMID- 2230044 TI - Group A streptococcal bacteremias associated with intravascular catheters. PMID- 2230045 TI - JCAHO infection control indicators, part 1. JCAHO Infection Control Indicators Task Force report. PMID- 2230046 TI - Current epidemiologic evidence and case reports of occupationally acquired HIV and other bloodborne diseases. AB - Studies in which noninfected persons shared households with human immunodeficiency virus (HIV)-infected family members and friends, and had substantial though non-sexual contact with them revealed no transmissions of the HIV virus. These results suggest a similar low risk for healthcare workers, particularly those who have little or no contact with blood. However, occupational transmission of HIV, when it does occur, is most commonly caused by needlestick injuries. Nurses make up the largest group--nearly 80%--of hospital workers who contract HIV infection on the job. Generally, the risk ratio following an HIV needlestick is 1 in 250. Improper needle disposal, recapping and other ingrained behavior patterns are typical causes of needlestick accidents. Though the focus today is on HIV/acquired immunodeficiency syndrome (AIDS), it is important to realize that hepatitis B accounts for 200 to 300 deaths a year among healthcare workers. Awareness of the risk of needlestick injuries, and the considerable financial and emotional costs they can impose, should justify preliminary expenditures on needlestick prevention programs. PMID- 2230047 TI - Risk reduction through testing, screening and infection control precautions--with special emphasis on needlestick injuries. AB - Transmission of the hepatitis B virus (HBV) and human immunodeficiency virus (HIV) pose substantial risks to institutional healthcare employees working with blood. While the risk of contracting hepatitis B in the hospital setting is much greater than the probability of acquiring HIV, the cost of treating the acquired immunodeficiency syndrome (AIDS)--if it develops--is much greater in both dollars and human suffering. In addition to the risks posed by the presence of HIV infection in the hospital increase daily. By the end of 1990, one of every 14 hospitalized patients will be an HIV carrier. Of all hospital-related injuries to employees, the highest percentage (35%) is caused by needlestick/"sharps" punctures. Over a 12-month period, approximately 18,000 hepatitis cases reportedly have been caused by needlestick accidents. After nurses, housekeeping personnel--victims of incorrectly disposed needles--are most at risk. Nurses incur 58% of needlesticks when needles are broken, cut or recapped. Currently, there are products on the market specifically designed to eliminate contact with needles. These cartridge-needle safety units allow for only one-time use, thus doing away with the possibility of recapping. Initial expenditures for new equipment are well worthwhile; the implementation of revised safety precautions are not only worthwhile but also required by law. The dollar costs imposed on hospitals by accidental transmission of bloodborne diseases include tests for the employee, treatment, outpatient visits and wages. One pilot study prevention program conducted in an 800-bed hospital resulted in a 53% reduction in needlestick injuries. PMID- 2230048 TI - The pharmacist's role in controlling bloodborne infections with emphasis on procuring safe injection systems. AB - The hospital's department of pharmacy plays an important role in lessening the risk of bloodborne disease transmission through its influences in the coordination and control of the hospital's drug distribution system, intravenous (IV) admixture service and purchasing decisions with regard to injectable drug products. A review of drug distribution systems has shown that the unit-dose system is the most advantageous in terms of accuracy, safety, time savings and overall costs to the institution. Needlestick injuries are an occupational hazard for healthcare workers. Today, the need for safety in medication administration is a priority in injectable medication systems. Pre-filled cartridges offer a number of advantages, one of which is their safety in preventing needlesticks, through facilitating administration of medication quickly and easily and disposal of the needle immediately thereafter. PMID- 2230049 TI - Adoption of guidelines for Universal Precautions and Body Substance Isolation in Canadian acute-care hospitals. AB - The impact of recently recommended hospital infection control guidelines on Canadian acute-care hospitals is unknown. A confidential cross-sectional mailed survey of all acute-care Canadian hospitals was conducted to determine rates of receipt and adoption of published guidelines for Universal Precautions (UP) or Body Substance Isolation (BSI), rationale for adoption and knowledge of costs and benefits. Five hundred and seventy-nine of 943 sites (61%) responded (exceeding 80% in urban centers); 94% among hospitals with at least 300 beds and 57% among those under 300 beds. Seventy-four percent of responders claimed adoption of UP (65%) or BSI (9%), staff protection being their primary motivation. Adoption of either UP or BSI was associated with size (p less than .001), increasing progressively from 45% in the smallest group (less than 25 beds) to 84% in the largest (greater than or equal to 500 beds). Many hospitals introduced modifications and some substituted names other than UP or BSI in adopting a new strategy. In practice, UP and BSI now mean different things in different hospitals, and the distinction between them has become blurred. Furthermore, only 5% claiming adoption of a new strategy adopted all of the fundamental policies expected under UP or BSI. Receipt of guidelines was also correlated with size: one-third of hospitals under 200 beds had not received key publications defining UP and BSI. Only 19% claiming adoption of a new strategy indicated knowledge of cost implications. These results suggest a need for closer collaboration among hospitals and government agencies in developing uniform infection control policies, and for systematic evaluation of the cost and effectiveness of new strategies. PMID- 2230050 TI - Influenza outbreaks in nursing homes: how effective is influenza vaccine in the institutionalized elderly? AB - During the 1984-1985 influenza season, outbreaks of influenza A (H3N2) occurred in three Connecticut nursing homes. Influenza vaccination rates were 67% (96 out of 144), 35% (30 out of 85) and 69% (332 out of 483), respectively. The relative risk of illness for vaccinated compared to unvaccinated residents was 1.8 (95% confidence interval, 0.6, 5.9), 1.6 (95% confidence interval, 0.8, 3.0) and 1.1 (95% confidence interval, 0.8, 1.7) for each of the three nursing homes, respectively. In the third outbreak, 22 vaccinated residents without clinical illness had a geometric mean titer of hemagglutination-inhibition (HI) antibody of 20. Although low, this titer was significantly higher than that of nine unvaccinated residents without clinical illness (12, p less than .05); only three (14%) vaccinated residents had HI titers of greater than or equal to 40. These results suggest that levels of HI antibody in vaccinated residents were not protective at the time of the third outbreak, four to five months after vaccination. In general, the study of vaccine effectiveness in nursing homes is limited by sample size and statistical power. Despite these limits, the retrospective investigation of influenza outbreaks in nursing homes is often the only practical way to evaluate influenza vaccine effectiveness in the elderly on a yearly basis. PMID- 2230051 TI - Frequent acquisition of multiple strains of methicillin-resistant Staphylococcus aureus by healthcare workers in an endemic hospital environment. AB - Methicillin-resistant Staphylococcus aureus (MRSA) has been an endemic nosocomial pathogen at the VA medical center (VAMC) in Providence, Rhode Island since 1981. From 1985 to 1987, more than 30% of all unique S aureus isolates were methicillin resistant. To evaluate the frequency of acquisition of MRSA isolates by healthcare workers, we compared the antimicrobial susceptibility patterns, multilocus enzyme genotypes and plasmid profiles of isolates recovered from nasal and hand cultures from VAMC nurses and house staff on rotation at the VAMC with those of clinical isolates from patients at the VAMC and four other affiliated hospitals. Fifty-six percent of ward nurses cultured (n = 112) were colonized with S aureus, of which 65% was methicillin resistant. Six isolates of MRSA were identified on the initial culturing of house staff (n = 65); 16 MRSA isolates were recovered at the end of a four-week rotation (p less than .02). Phenotypic and genotypic analyses demonstrated that numerous distinct MRSA strains were recovered in the study period. The incidence of MRSA among clinical isolates at the VAMC and affiliated institutions was remarkably constant throughout the three year study period. Moreover, despite regularly sharing resident physicians, interns and medical students, MRSA isolates were commonly recovered at the other university-affiliated hospitals. Our study failed to reveal evidence of significant interhospital transmission of MRSA isolates by healthcare workers. While healthcare workers may contribute to the dissemination of MRSA within institutions, they appear to be less important in spreading MRSA between institutions. PMID- 2230053 TI - Strongyloides stercoralis. AB - In many aspects, S stercoralis is a unique opportunistic pathogen. Via its autoinfections cycle, it is capable of producing both parasitic and bacterial infections at remote organ sites. These infections are often nosocomial. Diagnosis can be very difficult if appropriate microscopic evaluation is not done. Concomitant bacterial infections must be treated with appropriate antimicrobial agents; thiobendazole is the treatment of choice for the parasitic phase of these infections. PMID- 2230052 TI - Aztreonam. AB - Aztreonam, the first commercially available monobactam, has a wide range of activity against aerobic gram-negative bacilli. It can be administered two to three hours daily because its half-life is 1.6 to 2 hours. Excellent blood and tissue concentrations are attained. The MIC of aztreonam against most Enterobacteriaceae is less than or equal to 2 micrograms/ml and against P aeruginosa less than or equal to 16 micrograms g/ml. Aztreonam has been used in a wide array of infections of the urinary tract and respiratory tract, blood, intra abdominal and gynecologic infections and infections of the skin, bones and joints. As empiric therapy, aztreonam is usually combined with another antimicrobial agent active against anaerobes and/or aerobic gram-positive cocci until culture results are available. One exception is empiric therapy for gram negative urinary tract infections in which aztreonam can be used initially as monotherapy against susceptible gram-negative pathogens. In general, the efficacy of aztreonam is equal or superior to that of the aminoglycosides. Adverse reactions to aztreonam are unusual, and it as been shown to be a poor hapten, permitting its administration to patients with proven allergy to the penicillins and cephalosporins. Aztreonam is a useful addition to the available antibiotics for treatment of gram-negative infections. PMID- 2230055 TI - The dilemmas of introducing routine HIV testing into the intensive care unit. PMID- 2230054 TI - Blood pressure measurement: an evaluation of direct and indirect methods. AB - In order to evaluate the differences between the blood pressure values obtained by direct intraarterial (DM) and indirect sphygmomanometer (IM) measurements, both systems were employed in 30 patients during their immediate postoperative period (24 hours) at our Intensive Care Unite after open heart surgery. The total number of determinations was 355. The statistical study of data lead us to the following conclusions: 1. There are significant differences between arterial pressure values obtained by DM and IM falling within an acceptable range of error for clinical purposes 2. Both methods of measurement, direct and indirect, are highly influenced by technical details that have to be carefully standardised if suitable research values are to be obtained. PMID- 2230056 TI - Nursing for a patient requiring long-term care in an intensive care unit (ICU). AB - Nursing care in ICUs has frequently been discussed, and importance of psychological care for each patient has been recognised. The care of a severely ill patient who remained in the ICU in Japan for an extended time is described here. During his stay in the ICU, an expanded nursing programme was developed to minimise his mental exhaustion. While considering his pathophysiological condition nursing support was also designed to satisfy his basic desires and human needs, anticipating that this would have therapeutic effects and contribute to improvement of his general condition. Nursing care included particular emphasis on four areas of nursing intervention promoting mobility, and communication between the patient and his family and nurses. Exercise, food intake, sleep, and mental condition were carefully evaluated. The basic human desires of the patient (such as to eat, sleep, walk, etc) should be satisfied, taking into account the pathophysiological condition, even with a severely ill patient. Nursing care should focus on supporting the quality of life for patients, even in the ICU. PMID- 2230057 TI - The use of a multidisciplinary group meeting for families of critically ill trauma patients. AB - Family members of any trauma patient admitted to the Level I trauma center are invited by the trauma staff to attend weekly multidisciplinary meetings. By the use of these meetings, family concerns can become a positive care factor and the tasks of nurses, doctors and social workers alike made easier. PMID- 2230058 TI - Use of an implantable left ventricular assist device for irreversible ventricular fibrillation secondary to massive myocardial infarction--a case study. AB - Mechanical circulatory support devices are currently being developed. The indications for their use are presently following acute myocardial infarction; in post cardiac-surgical cardiogenic shock; and as a mechanical 'bridge' to cardiac transplantation. Devices are being developed for permanent implantation in patients with end-stage left ventricular failure who are unacceptable for or denied transplantation. Intensive care nurses are required to care for patients who receive such mechanical support. These patients need intensive physical care with extensive nursing intervention and psychological support. The following case study describes the care of a patient who received an implantable left ventricular assist device (LVAD). The study illustrates the nursing care required in the management of such patients. PMID- 2230059 TI - High technology and humanity for intensive care. AB - At surface level it is obvious that high technology and humanity are involved in intensive care, since many sophisticated biomedical techniques and machines are used, and all varieties of humankind may pass through intensive care units (ICUs). But it is important to give deeper consideration to the title topic, and it is proposed here to consider first high technology, then human aspects of intensive care, and the context which affects both. PMID- 2230060 TI - A double-blind placebo-controlled trial of zopiclone 7.5 mg and temazepam 20 mg in insomnia. AB - Zopiclone, a cyclopyrrolone with hypnotic properties was compared with temazepam and placebo in the treatment of insomnia. After a week's washout period, suitable subjects were allocated at random to zopiclone 7.5 mg or temazepam 20 mg or placebo for 2 weeks. Measurements of psychomotor function using the Leed's psychomotor tester and letter cancellation were carried out on day 0, 7 and 14. Sleep latency, duration of sleep and number of times waking during the night were recorded on a sleep diary filled by the subjects nightly. Forty-four subjects completed the trial, 15 taking zopiclone, 16 taking temazepam and 10 taking placebo. Both zopiclone and temazepam had significant hypnotic properties when compared to placebo. Zopiclone increased total sleep time in both weeks of the trial while temazepam increased sleep time in the first week only. There was no significant deterioration in psychomotor performance at the end of both weeks for zopiclone. Critical flicker fusion was significantly increased in subjects on temazepam. There were no abnormalities for both zopiclone and temazepam subjects in the blood picture, renal profile, liver function, urine and ECG before and after the study. Zopiclone is an effective hypnotic comparable to temazepam. PMID- 2230061 TI - Zopiclone and triazolam in insomnia associated with generalized anxiety disorder: a placebo-controlled evaluation of efficacy and daytime anxiety. AB - In a double-blind placebo-controlled study, following a 1 week washout, 75 outpatients suffering from generalized anxiety disorder with severe insomnia as the target symptom were randomly assigned to 4 weeks of treatment with zopiclone 7.5 mg, triazolam 0.5 mg or placebo at bedtime. Zopiclone was significantly better than placebo on most sleep parameters. Triazolam tended to be superior to placebo, but its superiority was significant only on the sleep induction factor. Triazolam-treated patients presented significantly more day-time-interdose anxiety than zopiclone as assessed by the weekly HARS and Clinical Global Assessment of Anxiety. Although daytime-interdose anxiety was observed with both drugs, this treatment emergent symptom was more frequent and severe with triazolam. Side-effects were of a mild to moderate intensity for both zopiclone and triazolam; however, taste perversion frequently appeared with zopiclone. Although both drugs share similar pharmacological properties and bind to benzodiazepine receptors, they differ significantly with respect to side-effects and daytime anxiety. PMID- 2230062 TI - Lofepramine, desipramine and abnormal tests of liver function: a case report. PMID- 2230063 TI - Adverse interactions encountered when using trazodone to treat insomnia associated with fluoxetine. AB - The authors report adverse interactions encountered when using low dose (25-75 mg) trazodone to treat insomnia associated with fluoxetine. Sixteen patients had good hypnotic responses to trazodone, but five needed to stop the medication due to excessive sedation. Three cases are described. PMID- 2230064 TI - The effects of codeine on human aggressive responding. AB - Ten healthy male research subjects received placebo, 25, 50 and 75 mg/70 kg of codeine in a controlled laboratory setting. During each session subjects had two response options. The non-aggressive response option was maintained by points exchangeable for ten cents. The aggressive response option ostensibly subtracted a point from the subject's fictitious partner. Aggressive responding was engendered by point subtractions attributed to a fictitious partner. Codeine did not significantly alter the frequency of monetarily reinforced, nonaggressive, responding. Aggressive responding was significantly increased at the 50 mg/70 kg dose of codeine. The frequency of aggressive responses during the placebo sessions preceding administration of the first codeine dose were significantly and positively correlated with scores on the Buss-Durkee Hostility Scale. Aggressive responding increased for four of five subjects scoring below the median on the Buss-Durkee Hostility Scale at the 50 mg/70 kg dose; while administration of 50 mg/70 kg increased aggressive responding of one subject who scored above the median. Aggressive responding for both groups of subjects was unaffected by the 75 mg/70 kg dose. PMID- 2230066 TI - Lithium and weight gain. AB - Lithium prophylaxis leads to weight gain in a high proportion of patients treated, with up to a quarter becoming clinically obese. This can have detrimental effects on compliance and is also a health risk. The mechanism of such lithium-induced weight gain is unknown, but increased calorie intake, particularly in the form of high calorie drinks, has been implicated. Remedial steps such as adjusting the lithium dose and giving appropriate dietary advice should be taken at the first sign of weight gain. PMID- 2230065 TI - Des-enkephalin-gamma-endorphin in the treatment of schizophrenia. AB - Ninety-three patients with an exacerbation of chronic schizophrenia were included in a 4 week trial comparing placebo with 1, 3 and 10 mg des-enkephalin-gamma endorphin (DE gamma E; beta-lipotrophin 66-77; Org 5878) per day (i.m.). Maintenance antipsychotic and other medications were continued unchanged. Treatment effects were assessed by means of the Comprehensive Psychopathological Rating Scale--subscale schizophrenia (CPRS-S), Brief Psychiatric Rating Scale (BPRS) and Global Assessment Scale (GAS) rating scales at weekly intervals. Safety data, i.e. laboratory investigations, vital signs and ECG recordings, were assessed before and during the trial. Side-effects were evaluated by means of a Record of Symptoms Emerging. Sixty-eight patients completed the trial, the reason for drop-out mainly being inadequate treatment effects and refusal of medication administration. One patient violated the protocol. After 4 weeks of treatment the mean CPRS-S score of the group receiving 10 mg DE gamma E daily had decreased statistically significantly more than the corresponding score of the placebo group (p less than 0.01). The same trend was apparent with BPRS (p = 0.08) and GAS (p greater than 0.1) scores. Therefore, the study should be considered inconclusive. No clinically relevant side-effects attributable to DE gamma E were observed. PMID- 2230067 TI - A controlled trial of adinazolam versus desipramine in geriatric depression. AB - Thirty outpatients between the ages of 60 and 85 with DSM-III Major Depression entered an 8 week randomized, double-blind comparison of desipramine and adinazolam mesylate, a triazolobenzodiazepine derivative. Outcome was assessed on several measures including the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Rating Scale, Clinical Global Impressions (CGI), the 35-item Self-Rating Symptom Scale, and Carroll Depression Scale. Patients in both groups demonstrated a highly significant decrease in average HDRS scores (p less than 0.001) over the course of the study. Adinazolam was associated with significantly greater reduction in average HDRS scores by the third day. Repeated measures analysis of variance showed a significantly greater reduction in HDRS scores for adinazolam over the course of the study. The study medications were associated with distinct patterns of adverse reactions. Desipramine more often produced dry mouth, constipation and nervousness, while adinazolam was more likely to cause drowsiness and lightheadedness. Three of these elderly patients, all of whom were taking desipramine reported at least one fall during the study. Adinazolam may be a promising agent in the treatment of depression in the elderly. PMID- 2230069 TI - Depression in the elderly. PMID- 2230068 TI - Diagnostic issues in depression in old age. PMID- 2230070 TI - Post-stroke depression. PMID- 2230071 TI - Treating refractory depression. PMID- 2230072 TI - Antidepressants: the implications of the cognitive and psychomotor effects in the elderly. PMID- 2230073 TI - Adverse effects of antidepressants. PMID- 2230074 TI - Depression in the elderly: pharmacokinetics of antidepressants and death from overdose. PMID- 2230075 TI - Affective disorder and physical illness in old age. PMID- 2230076 TI - Molecular genetic divergence of orang utan (Pongo pygmaeus) subspecies based on isozyme and two-dimensional gel electrophoresis. AB - The orang utan (Pongo pygmaeus), as currently recognized, includes two geographically separated subspecies: Pongo pygmaeus pygmaeus, which resides on Borneo, and P. p. abelii, which inhabits Sumatra. At present, there is no known route of gene flow between the two populations except through captive individuals which have been released back into the wild over the last several decades. The two subspecies are differentiated by morphological and behavioral characters, and they can be distinguished by a subspecies specific pericentric chromosomal inversion. Nei-genetic distances were estimated between orang utan subspecies, gorilla, chimpanzee and humans using 44 isozyme loci and using 458 soluble fibroblast proteins which were resolved by two-dimensional gel electrophoresis. Phenetic analysis of both data sets supports the following conclusions: the orang utan subspecies distances are approximately 10 times closer to each other than they are to the African apes, and the orang utan subspecies are approximately as divergent as are the two chimpanzee species. Comparison of the genetic distances to genetic distance estimates done in the same laboratory under identical conditions reveals that the distance between Bornean vs. Sumatran orang utans is 5-10 times the distance measured between several pairs of subspecies including lions, cheetahs, and tigers. Near species level molecular genetic distances between orang utan subspecies would support the separate management of Bornean and Sumatran orang utans as evolutionary significant units (Ryder 1987). Evolutionary topologies were constructed from the distance data using both cladistic and phenetic methods. The majority of resulting trees affirmed previous molecular evolutionary studies that indicated that man and chimpanzee diverged from a common ancestor subsequent to the divergence of gorilla from the common ancestor. PMID- 2230077 TI - An X-linked recessive mutation producing cleft palate, crooked tail, and polydactyly in mice. AB - Palate-tail-digits abnormality (ptd) is a new X-linked recessive mutation affecting the morphogenesis of the mouse. It maps proximal to Tabby. Hemizygous males and homozygous females exhibit skeletal malformations of the tail, polydactyly of the hind feet, and in about 60% of the cases a cleft palate. A very high level of postnatal mortality is observed even among the mutants without a cleft palate. PMID- 2230078 TI - From the museum. PMID- 2230079 TI - Balloon valvuloplasty. AB - Percutaneous balloon valvuloplasty has been used for several years for the treatment of stenosis of all four cardiac valves. It has been particularly effective in pulmonary stenosis in children and in rheumatic mitral stenosis, especially in the younger age groups without severe calcification. After initial enthusiasm, results have not been as good in severe calcific aortic stenosis, although there is a place for aortic valvuloplasty in patients who are truly inoperable for reasons of age or coexisting disease. The procedure also may be applicable to occasional cases of tricuspid stenosis. The techniques used and results obtained with these procedures at Indiana University are described. PMID- 2230080 TI - Peripheral cardiopulmonary support during high-risk angioplasty. AB - We report the safety and feasibility of the first three patients using cardiopulmonary bypass support at the Indiana University Medical Center during PTCA. All patients had severe left ventricular dysfunction. Cannulation was performed using 18- or 20-French cannulae of the femoral vessels, either surgically or percutaneously. After heparinization with an activated clotting time of greater than 450 seconds, cardiopulmonary bypass was instituted using the Bard CPS system. Flows ranged from 3.0 to 4.3 L/min. Normasol was used to prime the pump. Blood was retransfused back into the patient at the end of the procedure. Bleeding was a problem in case 1 at the arterial cannulation site and subsequently was corrected for cases 2 and 3. Coronary angioplasties were deemed technically successful. We conclude that high-risk angioplasty can be performed in patients with poor left ventricular function using cardiopulmonary bypass support in the cardiac catheterization laboratory. Further study is indicated. PMID- 2230081 TI - Transient ischemic attack: the presenting manifestation of transient asystole. AB - A patient with a focal transient neurologic deficit and no evidence of other underlying disease as an etiology is diagnosed with episodic asystole. His neurologic deficit was reproduced with episodes of asystole. The combination of asystole and localized intracranial atherosclerotic disease can produce focal neurologic deficits and should be considered in the differential for transient ischemic attack. It is easily preventable and responds to permanent implantation of a transvenous pacemaker. PMID- 2230082 TI - Abnormal catheter position after central venous line placement. PMID- 2230083 TI - Triscaphe arthritis. PMID- 2230084 TI - Maternal mortality in Indiana: a report of maternal deaths in 1988. PMID- 2230085 TI - HCFA administrator answers questions. PMID- 2230086 TI - Sentinel director explains review process. PMID- 2230087 TI - Undocumented phone calls: a liability issue. PMID- 2230088 TI - Pregnancy, abruptio placentae and cocaine. AB - Widespread cocaine use has caused concern about possible harmful effects during pregnancy. Several studies have suggested an increased incidence of abruptio placentae and stillbirths with cocaine use during pregnancy. This study examined what percentage of pregnant women in a lower socioeconomic population use cocaine, as well as positive urine cocaine screens in those with abruptio placentae and intrauterine fetal death (IUFD). Thirty patients were enrolled in the control group, eight in the abruptio placentae group and five in the IUFD group. One of 30 controls, one of eight in the abruptio placentae group and none of the IUFD group urines were positive for cocaine. A higher percentage of those in the abruptio placentae group had a history of abruptio placentae or fetal death, suggesting possible prior drug use. This group also had little, if any, prenatal care. Cocaine abusers may show signs of abuse in their obstetrical histories. PMID- 2230090 TI - Breast-feeding failure. PMID- 2230089 TI - Cardiac myxoma: the Indiana Heart Institute experience. AB - Surgical resection of a cardiac myxoma was performed in 14 patients at the Indiana Heart Institute at St. Vincent Hospital and Health Care Center in Indianapolis from 1974 to 1989. Thirteen were located in the left atrium and one in the right atrium. The 10 women and four men ranged in ages from 28 to 75 years. Surgical complications included one perioperative death, one late death and one late recurrence requiring reoperation. Physicians must be highly suspicious to correctly diagnose this unusual but surgically correctable entity. Two-dimensional echocardiography is the diagnostic technique of choice for both early diagnosis of a cardiac myxoma and late follow-up after resection. PMID- 2230091 TI - Intersection syndrome. PMID- 2230092 TI - National Practitioner Data Bank: what every physician should know. PMID- 2230093 TI - Defense of medical malpractice claims takes perseverance and patience. PMID- 2230094 TI - ICHIA offers insurance to high-risk patients. PMID- 2230095 TI - The Indiana Veterans Home and AIDS patients. PMID- 2230096 TI - [The individual variability of pyramidal neurons in the neocortex of the rat]. AB - In Golgi-Kopsch impregnated pyramid neurons of the neocortex (regio precentralis agranularis and area striata) of adult rats the individual variability was investigated. As parameters served the dendritic lengths, spine numbers and spine densities along the dendritic orders (basal and apical), within single dendritic fields, the apical and basal parts of the dendritic tree and of the whole neuron. The statistical tests gave the following results: Pyramid neurons in the regio precentralis agranularis are more variable than pyramid neurons in the area striata. Within the area striata the lamina III-pyramid neurons are more invariable than the lamina V-pyramid neurons. The basal dendrites are statistically more invariable than the apical dendrites. The dendritic lengths are less variable than the spine values. In general, the variability is different in particular subdivisions of the neurons analyzed as well as for the parameter chosen. The variability of neuronal structures depends from genetical factors and from a functional training. The knowledges about this variability are still insufficient. They are of considerable importance for the planning of experiments followed by statistical analyses. PMID- 2230097 TI - The effects of soft laser (He-Ne) irradiation on pineal parenchyma. Ultrastructural and pinealocyte caryometric modifications. AB - A study is made of the ultrastructure and variations in pinealocyte caryometric indices in 45 male albino rats (240 +/- 40 gm). Fifteen animals were subjected to exposed pineal body irradiation for 6 continuous minutes with soft He-Ne laser light. The irradiated rats were sacrificed in groups of five 3, 6 and 15 days post-irradiation. The control and sham-operated (craniotomy without irradiation) groups consisted of the same number of animals as the experimental groups. The results show a significant decrease in indices (p less than 0.0005) in all experimental groups in relation to the control and sham-operated animals, although in terms of the latter p for the three days post-irradiation group was 0.002. A progressive and significant decrease (p less than 0.002) was also observed between the experimental groups after 3 and 15 days and after 6 and 15 days, but not between the experimental groups after 3 and 6 days. Ultrastructurally, there were signs of secretory activity increase in the groups after 3 and 6 days, and decrease in such activity after 15 days--along with the appearance of cells of mesoglial lineage. A significant increase was observed in the number of peri-canalicular dark cells. The results are discussed and compared with those of other authors and different light energies. PMID- 2230098 TI - [Quantitative cytoarchitecture point differences in experimental cortical hemiatrophy found by automatic image analysis]. AB - For more than ten years automatic analysis procedures have been applied to explore cortical cytoarchitectonics of the brain. The investigations presented were carried out by a method described as "automatic morphocorticography". Attempts to find out quantitative criteria for early unilateral cortical alterations were carried out on a pig's brain with experimental cortical hemiatrophy caused artificially by wide spread meningeal fibrosis. Lateral differences of the relative volume density (V alpha) of all cells could be analysed for each cortical layer in detail by the automatically plotted morphocorticographs (MCG) of selected cortical parts from both hemispheres. Partial increases in the V alpha-values could be found in the whole cross-section of the cerebral cortex from the experimentally damaged hemisphere and the same value increases of between 10 and 15% were found in the 3rd an 5th cortical layer in particular. In contrast the mean values of the relative numerical cellular density in the whole cortical cross-section remained without significant changes. It can be concluded that the early alterations caused by this type of damage are predominantly due to changes in the neuropil structures. PMID- 2230099 TI - Development of the median eminence in the male mouse. Karyometric effect of neonatal and prepuberal castration. AB - We have studied the karyometric development of the ependymocytes of the median eminence and ependyma adjacent of the arcuate nucleus in a control group of male albino mice from the 5th to the 160th postnatal day, and in other two experimental groups of animals that were castrated at two different days: the first and the 20th day of life. We have found differences in the spontaneous development of both ependymocytes showing the median eminence ependyma a more closely relationship to changes of gonadal hormone levels around puberty. In both zones, the response of the ependymocytes to neonatal castration was clearly more significative than that obtained after prepuberal castration, with lower values in the castrated animals than in the control mice. We suggest that this could be related to nervous and hormonal mechanisms. PMID- 2230100 TI - NPY-like immunoreactivity in the brain of the teleost Tinca tinca (Cyprinidae). AB - The distribution of neuropeptide tyrosine (NPY) in the brain of the tench (Tinca tinca) was mapped immunohistochemically by the peroxidase-anti-peroxidase (PAP) technique. NPY-immunoreactive (NPYi) neurons were found in the nucleus entopeduncularis (ne). These perikarya were intensely immunostained and were surrounded by a large number of axons and fibre terminals. Additional immunoreactive neurons appeared in the nucleus dorsolateralis thalami (ndl) at the level of the commissura posterior (cp). Only a few scattered NPY-positive perikarya occurred in the nucleus ventromedialis (nvm) and in the nucleus posterior periventricularis (nppv). At more caudal levels immunoreactive NPY neurons were found in the nucleus lateralis valvulae of the dorsal tegmentum mesencephali. Besides some scattered neurons in the medulla oblongata the only immunostained neurons were located in a subependymal nucleus at the lateral border of the fourth ventricle. However, these perikarya were only weakly immunostained by the NPY-antiserum. From its location this cell group is considered as nucleus motorius nervi vagi (nmX). NPYi fibres and axon terminals were found in the bulbus olfactorius, in the dorsal and lateral areas of the telencephalon, in the near surrounding of the ne, below most of the hypothalamic nuclei, as a connection between the nucleus posterior periventribularis and the nucleus recessus lateralis, in the ventral hypothalamus, in the lateral parts of the pituitary and in the caudal diencephalic inferior lobe. NPY-fibres occurred in the medial and deep layers of the tectum opticum, in the marginal areas of the tegmentum and the torus semicircularis, and as a lateral fibre tract through the medulla oblongata, connecting to the rostral parts of the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230101 TI - Pattern of brain glucose utilization following magnetic stimulation. AB - The 2-deoxy-D-(14C) glucose technique was used for autoradiographic mapping of the local cerebral glucose utilization in pigeons which were exposed to a periodically inverted artificial magnetic field in the Earth's field range. Stimulation during daytime resulted in increased values particularly in primary or secondary visual structures. Stimulation during nighttime resulted in increased values in the optic tectum and within the nucleus isthmi. In both situations decreased values were determined in the hypothalamus and increased values in the pineal gland. The results support the concept that magnetic information is transduced by magnetoreceptors and is relayed to structures of the visual system. Moreover, it is suggested, that magnetic stimulation exerts suppressive metabolic effects on the basal hypothalamus. PMID- 2230102 TI - Tectal afferents in Rana pipiens. A reassessment questioning the comparability of HRP-results. AB - Studying afferents to the optic tectum in Rana pipiens by means of retrograde HRP transport, results were obtained, that cast doubt on the reliability of this neuronal tract tracing technique. The tectum was found to receive afferents from e.g. lateral mesencephalic tegmentum, torus semicircularis, contralateral large celled pretectal nucleus, and ipsilateral thalamic nuclei, which have not previously been demonstrated. In addition, the data obtained lack evidence of projections reported earlier. We suggest, that neuronal projections may be subject to hormone and/or activity dependent changes, that alter the probability of accumulating sufficient amounts of the tracer to become labeled. PMID- 2230103 TI - Electron microscopic observations of the trigeminal mesencephalic nucleus in the frog, Rana ridibunda. AB - The trigeminal mesencephalic nucleus (Mes V) of the frog Rana ridibunda, has been studied by means of electron microscopic techniques. Mes V neurons are large (20 30 microns in diameter). They are dispersed in the optic tectum and show round to oval cell bodies. Both multipolar and unipolar cells were observed. Their cytoplasm is very rich in organelles with well-developed rough endoplasmic reticulum that forms prominent and scattered Nissl bodies. Numerous small mitochondria, Golgi dyctiosomes, neurotubules and neurofilaments are distributed among the granular endoplasmic reticulum. A striking feature is the existence of abundant lysosome-like particles throughout the cytoplasm. In the surface of Mes V neurons spinous processes are absent and synaptic contacts on the perikarya are scarce. Two types of synapses, one with spherical translucent vesicles and the other with elongated translucent vesicles, contact on either the cell body or the dendrites of Mes V cells. PMID- 2230104 TI - The spinal terminals into the midbrain periaqueductal gray of the rat. A light and electron microscope study of the projections ascending via the ventro-lateral funiculus. AB - Light and electron microscope studies of the terminal fields of the spinal afferents ascending in the ventrolateral quadrant of the spinal cord to the periaqueductal gray matter (PAG) were carried out using silver degeneration techniques and anterograde WGA-HRP transport. At all mesencephalic levels the terminal degeneration and the labelling of the spinal fibres to the PAG were fairly dense, mainly concentrated in the outer part of the annular ring. At the electron microscope, the spinal nerve terminals were found ending almost exclusively in the neuropil, impinging on small dendritic profiles. The majority of these synaptic contacts were of the asymmetrical type and contained a prevalence of round vesicles. This study provides an accurate representation of the terminal domain of the spino-PAG afferents and gives the conclusive anatomical evidence that the fibres ascending in the ventro-lateral funiculus of the spinal cord do not simply pass through the PAG, but actually terminate in it, synapsing in the neuropil. PMID- 2230105 TI - Thalamic afferents from the brain stem. An experimental study using retrograde single and double labelling with HRP and iron-dextran in the rat. II. Nucleus laterodorsalis and subnucleus compactus nuclei pedunculo-pontini. AB - The reticulo-thalamic projection arising from the ncl. latero-dorsalis and from the subncl. compactus nuclei pedunculo-pontini was studied in single and double experiments using 51 injections of HRP and/or iron-dextran. The ncl. latero dorsalis projects to the midline nuclei, to the ncl. mediodorsalis and to the ncl. ventralis lateralis, and, together with the subncl. compactus, also to the anterior, intralaminar nuclei, to the ncl. ventralis basalis and ncll. posteriores. Part of the substantia grisea centralis pontis adjoining the oral pole of the ncl. latero-dorsalis sends out fibres throughout the region of the above listed nuclei while projecting only scantily to the anterior nuclei and to the ventrobasal complex. The projection from the ncl. laterodorsalis has a major contralateral component (about one third of the labelled cells) whereas the contralateral component arising from the subncl. compactus is very scanty. We found no topographic arrangement in the projection (though there were signs of a crude mediolateral organization). The projection, mainly from the ncl. latero dorsalis, shows relatively dense collateralization (double-labelled cells): ipsi- as well as contralaterally to the intralaminar nuclei, or collaterals to the ipsilateral intralaminary nuclei and, at the same time, to the contralateral ncl. mediodorsalis. A similar, albeit smaller collateralization, was also seen in the ncl. pedunculo-pontinus, its subncl. compactus: ipsilateral collateralization between the anterior and intralaminar nuclei or between the anterior and posterior intralaminar nuclei of the ipsilateral side. PMID- 2230106 TI - Immunohistochemical demonstration of serotonin neuron system in the central nervous system of the Japanese dogfish, Scyliorhinus torazame (Chondrichthyes). AB - The distribution of serotonin immunoreactivity in the brain of the Japanese dogfish (Scyliorhinus torazame) was studied with the peroxidase-antiperoxidase immunohistochemical method with serotonin antiserum. The somata of the serotonin neurons were located in the raphe regions of the brain stem and the spinal cord. A small number of serotonergic neurons were also distributed as cerebrospinal fluid contacting neurons in the organum vasculosum hypothalami (OVH) and the paraventricular organ (PVO). These neurons were classified into nine groups (S1 S9): spinal cord (S1), rhombencephalon (S2-S6), mesencephalon (S7), and prosencephalon (OVH, S8 and PVO, S9). Processes of the serotonin neurons were widely distributed in the central nervous system, forming dense networks in various regions. The highest concentrations of these fibers were in the dorsal area of the vagal lobe, the nucleus isthmi, the tuberculum posterium, the distal part of the PVO, and the dorsal regions of the olfactory tubercle. PMID- 2230107 TI - The influence of sexual orientation on career decision-making: a research note. AB - This study investigates differences between heterosexuals and homosexuals of both sexes with regard to several variables in the career decision-making process: anxiety about making a career choice, indecisiveness about the choice, need to acquire information about the career of choice, uncertainty about the choice, and career choice dissatisfaction. Significant interactions are found on choice uncertainty (gay men having the highest level of uncertainty and lesbian women the lowest) and choice dissatisfaction (heterosexual women and gay men showing more dissatisfaction than the other two groups). PMID- 2230108 TI - Aikane: accounts of Hawaiian same-sex relationships in the journals of Captain Cook's Third Voyage (1776-80). AB - The journals recorded by Captain James Cook and his associates on Cook's Third Voyage of discovery (1776-1780) include extensive eyewitness accounts and analyses of the Hawaiian people and their culture-the first to be made by Europeans and Americans. Among these are several reports of young men called aikane, who were attached to the court or train of the ali'i (chiefs), and whose functions were sexual, social, and political. Among these aikane were several who acted as intermediaries between the sailors and the Hawaiians, and whose influence and conduct profoundly affected the course of events at Kealakekua Bay, where Cook was killed in February, 1779. The information contained in these materials suggests that such Hawaiian same-sex relationships are more important than currently accounted for in accepted theories of Hawaiian ethnohistory. PMID- 2230109 TI - The Biblical prohibition of homosexual intercourse. PMID- 2230110 TI - Using Sexton to read Freud: the pre-oedipal phase and the etiology of lesbianism in Sexton's "Rapunzel". AB - In her poem "Rapunzel," Anne Sexton maps out a model of lesbian etiology that at once parodies the model proposed by Freud and significantly amends it. Freud's famous model for female development, as he articulates it first in "Some Psychological Consequences of the Anatomical Distinction Between the Sexes," and later in "Female Sexuality," may be profitably compared to the model implied by Sexton's poem. The female pre-Oedipal phase is crucially at stake in such a comparison, as Sexton's account suggests that the pleasures of the pre-Oedipal mother-daughter dyad are dangerously strong for the girl child, and seem to be the force that compels the majority of girls into the rechanneling of libidinal desire from the mother to the father. Sexton's poem emphasizes the continuous pressures exerted by the pre-Oedipal phase upon the psyche of the developing girl. Sexton's emphasis on the pre-Oedipal phase, and her depiction of heterosexual love, in "Rapunzel" and elsewhere, as regressive, suggests that the "normal" heterosexual female, who seeks a father figure in order to save herself from re-absorption into the primal mother-daughter dyad, is actually acting out an infantile fantasy of the devouring mother. The morbid irony of Sexton's "Rapunzel" stems from its depiction of a young woman who flees the boundary-less world of the pre-Oedipal state, only to resurrect the infantile fantasy of the devouring mother in the arms of a father substitute. PMID- 2230111 TI - The Multidimensional Scale of Sexuality. AB - Research on the assessment of sexual orientation has been limited, and what does exist is often conflicting and confusing. This is largely due to the lack of any agreed upon definition of bisexuality. The Multidimensional Scale of Sexuality (MSS) was developed to validate and to contrast six proposed categories of bisexuality, as well as categories related to heterosexuality, homosexuality, and asexuality. This instrument includes ratings of the behavioral and cognitive/affective components of sexuality. The MSS was completed by 148 subjects, the majority of whom were from identified homosexual and bisexual populations. Although subjects' self-descriptions on the MSS were consistent with their self-descriptions on the Kinsey Heterosexual-Homosexual Scale, the MSS provided a more varied description of sexual orientation. Subject's self described sexual orientation on the MSS was more consistent with their cognitive/affective ratings than with their behavioral ratings. With the exception of self-described heterosexuals, the frequency of cognitive/affective sexuality was greater than that of behavioral sexuality. PMID- 2230112 TI - An examination of demographic variables, nurturance, and empathy among homosexual and heterosexual big brother/big sister volunteers. AB - Potential volunteers are often screened for sexual orientation and, in most circumstances, excluded if they are gay men or lesbians. This is especially true if the volunteer's work involves children. Big Brothers/Big Sisters of San Francisco deviates from this practice and screens volunteers based on other attributes. This study investigates differences in demographic variables, nurturance, and empathy among homosexual and heterosexual Big Brothers/Big Sisters of San Francisco. Two hundred nineteen questionnaires were returned and results indicated that there were no significant differences in demographic factors, nurturance, or empathy based on sexual orientation. Gender differences for the study variables were found and these are consistent with the results of earlier studies. Three significant factors were identified: stability, social support and personality attributes. Sexual orientation was not a significant factor. PMID- 2230113 TI - Activation of murine T cells by streptococcal pyrogenic exotoxin type A. Requirement for MHC class II molecules on accessory cells and identification of V beta elements in T cell receptor of toxin-reactive T cells. AB - We investigated the mechanisms of murine T cell activation by streptococcal pyrogenic exotoxin type A (SPE A), focusing on the role of MHC class II molecules on accessory cells (AC) and V beta usage in alpha beta TCR of SPE A-reactive T cells in comparison with staphylococcal enterotoxin B-reactive T cells. L cells transfected with I-Ab genes functioned as effective AC for SPE A-induced responses by C57BL/6 T cells, proliferation, and IL-2 production, but control L cells were not effective AC. Anti-I-Ab mAb inhibited the SPE A-induced responses. Staphylococcal enterotoxin B-induced C57BL/6 T cell blasts were composed of cells bearing V beta 3, members of the V beta 8 family, and V beta 11. Most of the SPE A-induced T cell blasts (about 80%) bore V beta 8.2. mAb reactive to V beta 8.2 markedly inhibited SPE A-induced T cell responses. Apparently, SPE A activates mainly T cells bearing V beta 8.2 in physical association with MHC class II molecules expressed on AC. We also discuss the pathogenic activities of SPE A in relation to toxic shock syndrome. PMID- 2230114 TI - Hybridomas derived from lipopolysaccharide-activated anti-mu-treated B cells have active suppression of IgM secretion, demonstrable by secondary fusion. AB - Treatment of LPS-stimulated mouse B cells with bivalent anti-mu antibodies suppresses differentiation to Ig-secreting cells without interfering with proliferation. This treatment selectively inhibits up-regulation of transcription of differentiation-related genes. Induction of anti-mu suppression requires RNA and protein synthesis, suggesting involvement of a transcriptional repressor. We describe experiments designed to capture the repressed phenotype of anti-mu treated cells. Fusions of anti-mu-treated cells with the B lymphoma line M12.4.5, but not plasmacytoma Ag8.653, yielded a significantly lower frequency of secretory hybridomas than did parallel fusion of cells treated with LPS only. To test for active repression, nonsecreting cloned hybridomas were secondarily fused to LPS-activated normal B cells. Secondary hybridomas with anti-mu parentage had a very low frequency of IgM secretion. Active suppression could only be demonstrated by secondary fusion. Neither supernatants nor extracts of repressor hybridomas influenced LPS-driven differentiation of normal B cells. These results confirm that this form of differentiation suppression is an active process, probably mediated by transcriptional controls. Repressor hybridomas should prove useful for studies of molecular mechanisms. PMID- 2230115 TI - Development of B cell lineages during a primary anti-hapten immune response. AB - Cell lineage relationships were examined in large numbers of hybridomas derived from a single mouse at 7 days and from a single mouse at 12 days after a primary immunization. The properties of these developing lineages provide unique insight into their biologic selection and differentiation. The unique VDJ junctions, the characteristics of the somatic mutations, and the nonproductive H chain gene rearrangements observed at day 12 all indicate that the hybridomas were derived from a limited number of progenitor B cells. Clonally related hybridomas were also observed at day 7. The activation of these lineages occurred very early, because somatic variants were strongly selected for within a few days after the primary immunization. PMID- 2230116 TI - Aberrant regulation of IL-1 expression in macrophages from young autoimmune-prone mice. AB - IL-1 is a multifunctional, immunoregulatory polypeptide produced by many cell types. Because activated macrophages are a major source of IL-1 and have also been implicated in the pathogenesis of autoimmune disease, we investigated the regulation of IL-1 expression in several autoimmune-prone strains of mice. Peritoneal macrophages derived from the autoimmune-prone strains MRL/lpr, MRL/+, NZB, and NZB/W F1, as well as NZW, displayed transient expression of IL-1 in contrast to the stable expression characteristic of control normal strains including A. Thy, A/J, B10, B10.A, B10.D2, C57BL/6, BALB/c, and C3H/HeN. The down regulation of IL-1 by macrophages from the autoimmune-prone mice was not attributable to inherently defective signal transduction because macrophages from both the normal and autoimmune-prone strains displayed substantial initial levels of cell-associated and secreted IL-1. However, during the first 2 to 3 days in culture, macrophages from autoimmune-prone mice became progressively refractory to both induction and maintenance of IL-1, a pattern that correlated with changes in the levels of IL-1 alpha and beta mRNA. The progressive reduction in IL-1 expression by macrophages from these autoimmune-prone strains was not due to a reduction in general metabolism or viability, because expression of cell surface antigens, including MHC class I and II Ag and LFA-1, was comparable to that of control macrophages. Because IL-1 plays a critical role in the homeostasis of a variety of cell lineages, defective expression, and maintenance of IL-1 (and perhaps other cytokines) by macrophages from the autoimmune-prone strains may contribute to the immune dysregulation that develops in these mice. Alternatively, cytokine dysregulation might not contribute directly to disease, but rather reflect a more basic defect related to specific signal transducing or gene regulatory pathways. PMID- 2230117 TI - Immune responses of intact and embryonically enucleated frogs to self-lens antigens. AB - Embryonically enucleated frogs (Xenopus) will tolerate an isogeneic eye implanted during adult life although their immune system has never been previously exposed to eye-specific Ag. We hypothesized that such self-implants survive because they induce tolerance to the eye-specific Ag. We have developed evidence to support this hypothesis by studying the responses of embryonically enucleated or intact frogs, with or without eye implants, to self-lens proteins. After immunization with a low concentration of bovine lens proteins, spleen cells from all intact and all embryonically enucleated frogs displayed significant in vitro proliferation against the Ag. All animals in both groups of frogs also produced high titered xenoantibodies. After immunization with a comparable preparation and concentration of self-lens Ag, splenocytes from only some of the embryonically enucleated and intact frogs showed significant proliferation, and fewer of these frogs produced antibody. When the immunization protocol and Ag concentration were modified to evoke consistent anti-self-lens proliferative and antibody responses from enucleated frogs, intact frogs responded equally well. Because there were no significant differences in the magnitude of the responses, and the percent of enucleated and intact frogs responding did not differ, we conclude that there is little or no immunologic tolerance to self-lens Ag in intact frogs. When either embryonically enucleated or intact frogs were heterotopically implanted with isogeneic eyes and then immunized with self-lens Ag or foreign lens Ag using the optimal immunization protocol, the Ag-specific proliferative responses of their lymphocytes were significantly reduced after immunization with self-, but not foreign Ag. This argues that embryonically enucleated frogs can become tolerant of the organ-specific Ag of the lens, even in adult life. PMID- 2230118 TI - Control of IL-2 receptor-alpha expression by IL-1, tumor necrosis factor, and IL 2. Complex regulation via elements in the 5' flanking region. AB - We have analyzed the mechanisms by which IL-1, IL-2, and TNF regulate expression of IL-2R alpha chain in a rodent T cell line. All three cytokines induce detectable IL-2R alpha mRNA by themselves, but there is strong synergy between IL 1 or TNF, on the one hand, and IL-2, on the other. The earliest phase of induction by IL-1 is independent of protein synthesis. IL-1, but not TNF, also stimulates transient secretion of IL-2. This leads to an autocrine stimulation of a further increase in IL-2R alpha mRNA levels. When IL-2 secretion has dropped off, continued IL-2R alpha expression requires both IL-2 and IL-1. Most or all of this regulation is due to changes in the rate of transcription of the IL-2R alpha gene. The response to IL-1 and IL-2 depends on a segment in the IL-2R alpha 5' flanking region, upstream of all cis-acting regulatory elements previously identified in the human gene. PMID- 2230119 TI - A small proportion of cationic antibodies in immune complexes is sufficient to mediate their deposition in glomeruli. AB - Positively charged antibodies mediate enhanced deposition of circulating immune complexes at the glomerular basement membrane. The presented experiments demonstrate that when soluble immune complexes were prepared with a mixture of antibodies containing 10 to 25% cationic antibodies, then noncationic antibodies in the complexes were deposited in mouse glomeruli. One or two cationic antibodies in each immune complex sufficed for deposition of the complexes. Proof for this was obtained by two kinds of experiments. First, the injected immune complexes were prepared in Ag excess from mixtures of radiolabeled noncationic rabbit antibodies to human serum albumin (HSA) and unlabeled cationized rabbit antibodies to HSA, thus permitting the specific quantitation of the deposition of noncationic antibodies in glomeruli because of the presence of cationized antibodies within the same complexes. As a control experiment, immune complexes prepared only with noncationic antibodies resulted in very little deposition in kidneys over the same time period. Second, detection of the localization of the noncationic antibody in deposits in glomeruli by immunofluorescence microscopy was accomplished using immune complexes prepared with mixtures of noncationic goat antibodies to HSA and cationized rabbit antibodies to HSA. Thus, the synthesis of a small population of cationic antibodies during the immune response may lead to the formation of circulating immune complexes with enhanced propensity for deposition in glomeruli in patients with SLE or other immune complex diseases. PMID- 2230120 TI - Ultraviolet cross-linking of helical oligonucleotides to two monoclonal MRL 1pr/1pr anti-DNA autoantibodies. Variations in H and L chain binding to DNA. AB - Experiments were performed to determine whether both H and L chains of different anti-native DNA autoantibodies are uniformly involved in binding to DNA. Two purified monoclonal mouse (MRL-1pr/1pr) IgG autoantibodies, H241 and 2C10, were tested. They both bound synthetic helical oligonucleotides of 10 to 20 base pairs in a gel electrophoresis retardation assay but differed in their preferences for given base sequences. Exposure of antibody-radiolabeled oligonucleotide mixtures to UV light (254 nm) for 10 min led to specific covalent cross-linking of oligonucleotide to both the H and the L chains of H241 but only to the H chain of 2C10. Single labeling events were detected without higher aggregation. The oligonucleotides were not cross-linked to unrelated IgG, even after 2 h of irradiation. Cross-linked (radioactively labeled) H and L chains of H241 and 2C10 were isolated from denaturing electrophoresis gels and digested with lysyl endopeptidase and/or staphylococcal V8 protease. H241 and 2C10 H chains each yielded a major labeled peptide fragment, but the peptides from the two antibodies were different. These experiments measured only some of the antibody DNA interactions, probably with bases in the major groove of the DNA. They indicated that two MRL-1pr/1pr IgG anti-native DNA antibodies differ in their H and L chain contacts with DNA and provide an approach to identifying affinity labeled binding sites in the antibodies. PMID- 2230121 TI - Binding of staphylococcal enterotoxin A to purified murine MHC class II molecules in supported lipid bilayers. AB - The staphylococcal enterotoxins are a family of bacterial toxins that are thought to exert their pathogenic effects by the massive activation of T lymphocytes to produce lymphokines. Activation of T cells by these toxins is dependent on MHC class II+ APC. Recent studies from a number of laboratories have implicated MHC class II proteins as the APC surface receptor for a number of the staphylococcal enterotoxins. The present report shows that staphylococcal enterotoxin A, (SEA) binds to the purified murine MHC class II molecule I-Ed reconstituted in supported planar membranes, indicating that no other cell surface proteins are required for SEA binding. The Kd for SEA binding to I-Ed was determined to be 3.5 +/- 1.6 x 10(-6) M. Specific binding of SEA to I-Ad was also observed, but the interaction was of significantly lower affinity. Binding of SEA to purified I-Ed was blocked by antibodies against both the alpha- and the beta-chain of the I-Ed molecule, but not by antibodies specific for an unrelated MHC class II protein. Binding of SEA to I-Ad was blocked by an A beta d but not by an A alpha d specific antibody. Planar membranes containing only lipid and purified I-Ed molecules were sufficient for activation of a V beta 1 expressing T hybrid by SEA. The T cells responded to as few as 180 toxin molecules per T cell. PMID- 2230122 TI - Bacterial killing and inhibition of inner membrane activity by C5b-9 complexes as a function of the sequential addition of C9 to C5b-8 sites. AB - The assembly of the C5b-9 complex on the outer membrane of C-sensitive cells of Escherichia coli results in a rapid inhibition of inner membrane function and ultimately a loss of cell viability. Cells bearing C5b-8 sites suffer no deleterious effects; however, the addition of C9 results in a rapid inhibition of inner membrane function and cell death. An attempt was made to examine the relationship between the toxic effects of the C5b-9 complex and the number of C9 molecules per C5b-8 site. Cells bearing C5b-8 sites were exposed to excess C9 at 0 degrees C and washed three times at 4 degrees C. The number of C9 molecules bound to each cell was equivalent to the number of C5b-8 sites present on each cell, and no additional C9 molecules could be bound when the cells were maintained at 4 degrees C. These cells were then incubated at 37 degrees C for 3 min and returned to 0 degrees C, a technique which exposed additional C9-binding sites equivalent to the number of C9 molecules previously bound to the cells. This technique was repeated and demonstrated that the sequential build-up of a C5b-9 site with two C9 molecules per C5b-8 site was capable of inhibiting both inner membrane function (respiration and amino acid transport) and cell viability. Three C9 molecules per complex had effects that approached the inhibitory effects of complexes formed in the presence of excess C9. PMID- 2230123 TI - Proteolytic fragmentation of sialophorin (CD43). Localization of the activation inducing site and examination of the role of sialic acid. AB - Sialophorin (CD43) is the major surface mucin on many hematopoietic cells. It has been implicated in regulating the survival of T lymphocytes in the circulation, and its functions in vitro as the receptor of a T lymphocyte and monocyte activation pathway. The structure of CD43 was examined by protease treatment of lymphoblastoid cells bearing surface CD43. Trypsin treatment converts CD43 (apparent Mr 115,000) to species of apparent Mr 100,000 called T-100, which remains cell-associated; however, the mechanism of trypsin action was not clarified. Pancreatic elastase and Staphylococcus aureus V8 protease cleave CD43 at discrete extracellular sites. V8 protease generates two fragments, which together account for all properties and mass of the parent molecule. The COOH terminal fragment V-90 (apparent Mr 90,000) consists of the intracellular and transmembrane regions and part of the extracellular region. The fragment V-30 (apparent Mr 30,000), which is released from the cell, comprises the NH2-terminal approximately 78 amino acids with attached oligosaccharides. V-30 contains the binding sites for the antibodies L2 and L10; the latter is the antibody that activates lymphocytes and monocytes. These findings subdivide the extracellular region of CD43 and indicate that the activation-inducing epitope is located in the most distal portion of the molecule. It is shown that CD43 is insensitive to all but very high concentrations of three proteases. Pretreatment with sialidase enhances sensitivity 13-fold for trypsin, 40-fold for S. aureus V8 protease, and 400-fold for elastase, suggesting that sialic acid influences the survival of surface CD43 molecules when cells are exposed to protease. PMID- 2230124 TI - Protein D of Haemophilus influenzae. A novel bacterial surface protein with affinity for human IgD. AB - Protein D, a novel surface protein of the bacterial species Haemophilus influenzae with affinity for human IgD, was isolated after solubilization with sonication and Sarcosyl-extraction by a single SDS-PAGE step. From 1 ml of packed bacteria was prepared 0.25 mg of purified protein D. The apparent m.w. of protein D was estimated to 42,000 by SDS-PAGE and gel chromatography. Edman degradation cycles of protein D produced no amino acid phenylthiohydantoin derivatives and the amino-terminal end of the single protein D polypeptide chain is thus probably blocked. Protein D differs from all previously described outer membrane proteins (protein 1 to 6) of H. influenzae. Thus, protein D did not react with antibodies against protein 1 or protein 2 and the latter proteins did not bind IgD. Protein D was found to exhibit unique Ig-binding properties. Thus, in dot blots protein D bound four different human IgD myeloma proteins but not IgG, IgM, IgA, IgE, or some additional proteins. On the IgD molecule, constant parts of the H chains both in the Fab and Fc fragments appear responsible for the interaction with protein D. This novel Ig-binding reagent promises to be of theoretical and practical interest in immunologic and microbiologic research. PMID- 2230125 TI - Monosodium urate crystals stimulate phospholipase A2 enzyme activities and the synthesis of a phospholipase A2-activating protein. AB - Eicosanoids are important mediators of the inflammatory response to monosodium urate crystals (MSUC) that results in gout. Phospholipase enzymes cleave fatty acids from membrane phospholipids, and this is thought to be the rate-limiting step in eicosanoid production. To understand better the mechanism of eicosanoid production in this disease, we stimulated human peripheral blood neutrophils and monocytes with MSUC and measured phospholipase enzyme activities. MSUC stimulated both intracellular and secretory phospholipase A2 enzyme activities in a time and concentration-dependent manner. Specificity was observed, as phospholipase C activities were not affected. Pretreatment with colchicine, but not aspirin, indomethacin, allopurinol, or islet activating protein, abrogated the enhanced phospholipase A2 activities. We have recently isolated and characterized a phospholipase A2 activating protein termed PLAP from synovial fluid from patients with rheumatoid arthritis, and from murine and bovine cell lines. PLAP was detected in gouty synovial fluid by immunodot blotting and ELISA assays and expressed the same characteristics as PLAP identified from other sources. To examine the role of PLAP in MSUC-induced phospholipase A2 stimulation, we treated cells with MSUC and observed an increase in immunoreactive PLAP. This response also could be blunted by colchicine, but not other drugs. Both phospholipase A2 and PLAP induced production by human monocytes of PGE2 and leukotriene B4 by neutrophils. These findings suggest that phospholipase A2 activation in response to MSUC requires an intact microtubule structure, and that phospholipase A2 and PLAP may be important modulators of at least a portion of the gouty inflammatory response. PMID- 2230126 TI - Developmental expression of plasminogen activator inhibitor type 1 by human alveolar macrophages. Possible role in lung injury. AB - Urokinase activity is regulated by the specific endogenous plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2). One of these inhibitors, PAI-1, has been directly implicated in connective tissue metabolism by virtue of its ability to bind extracellular matrix proteins. Because the normal lung is relatively rich in urokinase and abnormalities in urokinase activity have been associated with fibrotic lung diseases, we have explored the possibility of local production of PAI-1 and PAI-2 in human lung. Reverse transcription and subsequent amplification by the polymerase chain reaction of total lung RNA revealed PAI-1 mRNA in each of three normal samples and in two specimens from patients with the adult respiratory distress syndrome (ARDS). In situ hybridizations of lung biopsy specimens from a patient with ARDS with cRNA probes to PAI-1 and PAI-2 indicated that alveolar macrophages express PAI-1 mRNA during the acute injury phase. Subsequent reverse transcription and PCR amplification of normal human monocyte and alveolar macrophage mRNA revealed that neither cell type expressed mRNA for urokinase inhibitors. However, after 24 h stimulation with endotoxin in vitro, monocytes were strongly positive for PAI-2 but negative for PAI-1 mRNA whereas, under the same conditions, alveolar macrophages exhibited mRNA for both PAI-1 and PAI-2. Metabolic labeling of endotoxin-stimulated alveolar macrophages with 35S methionine followed by immunoprecipitation with PAI-1 and PAI-2 antibodies revealed that macrophages synthesized both PAI-1 and PAI-2. As judged by immunoprecipitation and functional studies, PAI-2 was found to be the major intracellular PA inhibitor whereas PAI-1 was found to predominate outside the cell. Thus, mononuclear phagocytes exhibit a developmental potential for PAI-1 expression. The release of PAI-1 by stimulated macrophages, as observed in the setting of ARDS, may be one mechanism by which these cells promote connective tissue accumulation. PMID- 2230127 TI - Failure to detect IL-3-binding sites on human mast cells. AB - IL-3, a pleiotropic lymphokine, has been termed mast cell growth factor because it promotes growth and differentiation of murine mast cells. Murine mast cells, in turn, express cell surface receptors for IL-3. Human rIL-3 has been shown to induce proliferation and differentiation of human basophils and to activate basophils via high affinity binding sites. To investigate whether human mast cells express IL-3R, binding studies with 125I-radiolabeled human rIL-3 were performed on HMC-1, a novel human mast cell line, and on pure populations (i.e., 93 to 99% purity) of human tissue mast cells obtained with mAb and C from dispersed lung (n = 2). Unexpectedly, neither enriched human lung mast cells nor HMC-1 cells bound radiolabeled human rIL-3 specifically. Moreover, human rIL-3 failed to promote uptake of [3H]thymidine, synthesis of histamine, histamine releasability, or changes in expression of mast cell differentiation Ag (YB5B8, CD54/ICAM-1, CD9/p24, CD33/gp67) on either human lung mast cells or HMC-1 cells. It is hypothesized that the fundamental difference in the biologic response to IL 3 between human and murine mast cells is due to a loss during evolution of mast cell high affinity IL-3 binding sites. PMID- 2230128 TI - Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. AB - The proliferative response of PBMC to hepatitis B virus (HBV) envelope, core, and e Ag was analyzed prospectively in 21 patients with acute self-limited HBV infection and compared with the response of patients with chronic HBV infection and different levels of HBV replication (i.e., hepatitis e Ag (HBeAg)- or anti HBe-positive) and liver damage (i.e., chronic active hepatitis or chronic asymptomatic carriers). Our results indicate that: 1) HBV-infected subjects who develop a self-limited acute hepatitis show a vigorous PBMC response to hepatitis B core Ag and HBeAg, as expression of T cell activation; 2) appearance of a detectable lymphocyte response to HBV nucleocapsid Ag is temporally associated with the clearance of HBV envelope Ag; 3) in patients with chronic HBV infection the level of T cell responsiveness to hepatitis B core Ag and to HBeAg is significantly lower than that observed during acute infection; 4) T cell sensitization to HBV envelope Ag in acute and chronic HBV infection is usually undetectable and when measurable is expressed transiently and at low levels. These results may reflect immune events of pathogenetic relevance with respect to evolution of disease and viral clearance. PMID- 2230129 TI - The kinetics of gene expression and maturation of IL-1 alpha after induction with the surface coat of Trypanosoma brucei rhodesiense or lipopolysaccharide. AB - The purpose of this study was threefold: to determine if the variant surface coat glycoprotein (VSG) of Trypanosoma brucei rhodesiense induces IL-1 alpha; to study the kinetics of IL-1 alpha transcription, maturation and secretion; and to compare VSG to LPS in its ability to induce IL-1 alpha. VSG was added to cultures of the P388D1 murine macrophage cell line. RNA was dotted onto nitrocellulose and hybridized with a murine IL-1 alpha cDNA probe. Maximal production of IL-1 alpha mRNA occurred in a dose- and time-dependent manner, peaking at 25 micrograms/ml VSG, within 2 h. Induction of IL-1 alpha was not due to contaminants because 1) absorption of VSG with a mAb abrogated IL-1 alpha mRNA synthesis, 2) the addition of polymyxin B did not affect mRNA levels, and 3) cellular IL-1 alpha was detectable in VSG-treated splenocytes from endotoxin nonresponder C3H/HeJ mice. Murine splenic macrophages also had enhanced levels of IL-1 alpha mRNA after administration of VSG in vivo or during an acute infection. Antiserum generated against the synthetic peptide SGDDSKYPV (amino acids 177-185 from the murine IL-1 alpha sequence) was used to measure the levels of the 33-, 22-, and 14-kDa proteins in cell lysates and medium of VSG-stimulated P388D1 cells. The 22-kDa protein was the predominant cellular form until secretion started. Secretion of the 14-kDa form began abruptly 6 to 8 h after the addition of VSG. By 12 h, the 33-kDa precursor was the major cytoplasmic form. In comparative analyses, LPS stimulated P388D1 cells produced more transcript, generated peak levels of 22-kDa protein 3 h earlier, and began to secrete the 14-kDa molecule 5 h earlier. The rate of IL-1 alpha accumulation in the medium was linear between 6 and 24 h after LPS treatment, but began to drop by 8 h in VSG-treated cells. Functional (comitogenic) IL-1 activity was also detected in media from VSG-treated splenic macrophages and P388D1 cells. Activity peaked at 50 micrograms/ml and was lost if 0.2% IL-1 antisera were added to the cultures. PMID- 2230130 TI - Analysis of beta 2-microglobulin gene expression in the developing mouse embryo and placenta. AB - The major transplantation (MHC) Ag in the mouse are cell-surface glycoproteins composed of a 40- to 45-kDa H chain and a 12-kDa L chain, beta 2-microglobulin (beta 2 m). Regulation of MHC gene expression during early development is thought to play a critical role in maternal tolerance of the fetal allograft. We have used in situ hybridization techniques to characterize the temporal and spatial pattern of expression of the beta 2 m gene in the developing mouse embryo. beta 2 m mRNA is first detected in the extra-embryonic derivatives of the early primitive streak stage embryo where it is specifically restricted to the tissues of the ectoplacental cone and chorion. Expression of the beta 2 m gene continues in these tissues during formation of the definitive placenta. beta 2 m transcripts were also detected in the tissues of the visceral yolk sac starting at 10.5 days. Comparable levels of expression were observed in both the visceral yolk sac endoderm and the extra-embryonic mesoderm. These results clearly indicate that the onset of beta 2 m gene expression is not restricted to early hemopoietic cells. In the embryo-proper, significant levels of beta 2 m mRNA were not detected until day 9.5. At this stage, we observed a strong signal over the liver rudiment. The remaining somatic tissues expressed low levels of transcripts. Similar results were obtained at later stages of development, i.e., the fetal liver was consistently the most strongly positive organ. Overall these in situ hybridization studies define the pattern of beta 2 m gene transcription and thus potential sites of surface expression of class I proteins in specific cell lineages in the early postimplantation stage embryo. PMID- 2230131 TI - Syrian hamsters express diverse MHC class I gene products. AB - MHC class I glycoproteins are highly diverse in most species. The Syrian hamster has long been thought to express monomorphic MHC class I molecules and thus be an exception to this rule. Here we show that Syrian hamsters express diverse MHC class I gene products. The nucleotide sequences of the alpha 1 and alpha-2 domains of classical Syrian hamster MHC class I molecules are highly variable and show evidence of having been under selective pressures at their Ag recognition sites. Interestingly, none of the Syrian hamster class I genes was closely related to their counterparts in the mouse. These observations suggest that Syrian hamsters in the wild may express diverse MHC class I molecules. PMID- 2230132 TI - Insulin-like growth factor-I supports proliferation of autocrine thymic lymphoma cells with a pre-T cell phenotype. AB - We have studied the phenotypic characteristics and growth properties of murine T lymphoma cell lines derived from primary x-ray-induced thymic lymphomas at the earliest stage at which they can be detected, and well before spreading to other organs has occurred. These cell lines serve as model systems for the earliest events in T cell lymphoma induction, before tumor cell progression and spreading to other organs. We find that primary x-ray-induced T cell lymphoma lines have phenotypic characteristics of thymic pre-T cells and show no proliferative response to any of the IL tested nor to other hematopoietic growth factors. However, they do proliferate in response to insulin-like growth factor I (IGF-I) and to a small autocrine peptide distinct from IGF-I, which we term lymphoma growth factor. One of the earliest lesions in T cell lymphoma induction may therefore be an inhibition of differentiation at one of several specific points. In its early stages, T lymphoma cell growth may be restricted to an environment where local concentrations of specific growth factors such as IGF-I or lymphoma growth factor are sufficiently high. PMID- 2230133 TI - Isolation of a novel tumor protein that induces resistance to natural killer cell lysis. AB - The human metastatic tumor cell line CAP-2, produces a soluble factor that induces resistance to NK lysis of K-562 susceptible leukemia cell line, and does not inhibit the cytotoxic capacity of effector cells. The use of sequential HPLC, hydrophobic interaction chromatography, and reverse phase chromatography, coupled with cytotoxic assays, resulted in the isolation and separation to homogeneity of a novel protein responsible for this biologic activity. Size estimation studies based on TSK HPLC columns showed that this protein has a mass of 8 to 12 kDa. The amino acid composition analysis of the CAP-2 protein calculated from HPLC chromatograms shows that this protein contains around 108 amino acids. Subsequent gas phase sequence analysis, however, was hampered because the N terminus of this protein was blocked and therefore unsuitable for sequencing by Edman degradation. The functional studies showed that the NK lysis-resistance activity of the CAP-2 protein is mediated by interaction with and nonspecific binding to NK target cells. The lymphokine-activated killer and macrophage-mediated cytotoxicity and mitogen-induced proliferation is not affected. Unexpectedly, the CAP-2 protein appears to be mitogenic to its own cell line. Thus, the induction of NK lysis resistance and the mitogenic activity showed by CAP-2 protein could contribute to the tumor growth and metastatic establishment. PMID- 2230134 TI - The sensitivity of dot immunoassay for the peptides helodermin, histidine isoleucinamide (PHI) and histidine-methioninamide (PHM) increases after peptide cross-linking to proteins prefixed on nitrocellulose. AB - Two out of three rabbit anti-helodermin antisera previously shown to be useful for radioimmunoassay failed to detect up 100 ng of the peptide helodermin spotted directly on a nitrocellulose membrane. A lesser shortcoming of dot immunoassay was encountered with porcine PHI (peptide histidine-isoleucinamide), a member of the same peptide family, and an anti-PHI antiserum. To improve antigen-antibody interactions in the solid phase, we compared five methods of prior peptide immobilization. The best result was obtained when the nitrocellulose membrane was pretreated for 1 min in 4% ovalbumin, followed by 10 min activation with 2.5% glutaraldehyde, before peptide spotting. After cross-linking, the peptide was immunodetected with a F(ab')2 fragment of an anti-rabbit IgG coupled to alkaline phosphatase. The peptide cross-linking method was capable of increasing the sensitivity of ensuing immunodetection by more than 1000-fold, i.e., made feasible the detection of 0.1 ng peptide/dot in cases when the direct spotting method was inefficient. The sensitivity of this new, reliable and simple dot immunoassay for peptides was comparable to the conventional dot assay of directly immobilized large proteins. PMID- 2230135 TI - Antigen protection of monoclonal antibodies undergoing labelling. AB - The effectiveness of a methodology designed to protect the antigen binding capacity of monoclonal antibodies undergoing labelling with a number of reagents was examined. The antigen binding sites of monoclonal antibodies were protected by complexing them with their antigen. Chemical modification with 6 mM of the water soluble Bolton-Hunter reagent of site protected monoclonal antibodies to glucoamylase resulted in antibodies that could tolerate a four-fold increase in reagent incorporation, without any loss of antigen binding capacity. Iodination of these antibodies (modified under site protected conditions) yielded over 70% increase in radioactivity incorporated in the active antibody fraction, compared with the incorporation into unprotected antibodies. Site protected labeling was found to be effective in retaining the antigen binding capacity of monoclonal antibodies modified with all reagents tested with the exception of chloramine-T. PMID- 2230136 TI - An immunoassay for the quantitation of cell membrane MHC class II antigen. AB - A method is described for the quantitative assay of cellular MHC class II proteins. The assay has been developed for special use with epithelial cells isolated from the intestine, but has been successfully used with other cell types. It comprises a competitive immunoassay of anti-class II activity in cell lysates, using IgG-coated Sephacryl S300 as the solid phase and is sensitive over the range 1 ng-1 microgram. PMID- 2230137 TI - A chemiluminescent, microparticle-membrane capture immunoassay for the detection of antibody to hepatitis B core antigen. AB - A chemiluminescent, microparticle-membrane capture immunoassay (CLIA/MMC) for the detection of antibody to hepatitis B core antigen (anti-HBc) is described. The assay utilizes recombinant hepatitis B core antigen coupled to carboxylated latex microparticles. Human polyclonal IgG anti-HBc labelled with acridinium competes with antibody in the sample for a limited number of binding sites on the solid phase. After a 40 min incubation at 40 degrees C, the reaction mixture is transferred to a glass fiber capture membrane and washed. A chemiluminescent signal is produced by addition of alkaline peroxide and is quantitated on a semi automated reader as described. The CLIA/MMC assay was compared with standard EIA and RIA procedures (Corzyme and Corab, respectively, Abbott Laboratories, North Chicago, IL). Assay sensitivities were RIA greater than CLIA/MMC greater than EIA. A population of 200 normal blood donors showed nearly identical distributions with the CLIA/MMC and RIA (mean = 11% inhibition, SD = 13% for both), compared with the EIA (mean = 13% inhibition, SD = 15%). With a selected plasma population (n = 307), the CLIA/MMC immunoassay showed an excellent correlation (r = 0.94) with both the EIA and RIA procedures. Association of anti HBc reactivity near assay cutoffs with antibody to hepatitis B surface antigen suggested relative specificity in the order RIA greater than CLIA/MMC greater than EIA. The CLIA/MMC procedure, which can be readily automated, provides a non istopic alternative to current EIA testing with performance more nearly equivalent to RIA. PMID- 2230138 TI - Functional assay of C5-activating and nonactivating cobra venom factor preparations in the mouse system. AB - This paper deals with a new, functional assay of cobra venom factor (CVF) preparations with or without C5-activating property. Existing methods lack sensitivity and use diluted human complement as target of inactivation. An adapted assay using diluted mouse serum as complement source was hampered by underestimation of C3 depletion by bystander lysis and an overvaluation of C5 consumption resulting from C3 inactivation in the reagent used. These disadvantages prompted us to develop the new assay which is based on the incubation of CVF preparations with undiluted mouse serum. After incubation, residual total C activity, as well as functional C3 and C5 are estimated by titration. The procedure permits the assessment of CVF activities with minimal interference from undesired processes. The conditions in the new assay approach the in vivo situation in mice by the use of undiluted serum from the same animal species. PMID- 2230139 TI - Effect of hapten heterology on thyroid hormone immunoassays. AB - We examined the effects of hapten heterology on triiodothyronine (T3) and thyroxine (T4) immunoassays configured with protein-conjugated diiodothyronine (T2), T3 or T4, using acridinium ester (AE) as a chemiluminescent label and paramagnetic particles (PMP) as a solid phase. Assays constructed with hapten heterologous combinations, such as immobilized anti-T4 plus labeled T3 or immunobolized anti-T3 plus labeled T2, were superior to the homologous ones in their potential for attaining higher sensitivity. This was manifested in a shift of the displacement curves to lower analyte concentrations, accompanied by unexpectedly high bound-tracer/total-tracer (B/T) ratios. This effect of hapten heterology was apparent with the use of either monoclonal or polyclonal antibodies and did not depend upon which component (antibody or protein conjugated hormone) was immobilized on the solid phase. In contrast, heterologous displacement curves with unconjugated hormone (125I-labeled) or with a labeled Fab fragment exhibited both a shift to lower analyte concentration and the expected decrease of B/T ratios. These results can be explained by the existence of positive binding cooperativity in the interaction between antibodies and haptenated proteins. Assay specificity was not adversely affected by hapten heterology when utilizing monoclonal antibodies, and hormone levels measured in serum samples correlated well with values obtained in homologous immunoassays. PMID- 2230140 TI - A comparison of immunoblotting, flow cytometry and ELISA to monitor the binding of anti-lipopolysaccharide monoclonal antibodies. AB - This study was designed to assess the use of flow cytometry to observe the binding, under physiological conditions, of anti-lipopolysaccharide (LPS) monoclonal antibodies (mAbs) to whole bacteria, and to compare this with the more conventional whole cell ELISA and immunoblotting techniques. The bacteria consisted of two clinical isolates of E. coli 018:K1 and 06:K5 and two isogenic mutants of the 018 parent: a non-capsulate (018:K-) and a rough mutant (018rf). Two cross-reactive anti-core mAbs and one 018 0-antigen-specific mAb were used. ELISA and flow cytometry showed that capsule and O-polysaccharide influenced the binding of mAbs to the bacteria, whilst the latter technique demonstrated that sub-populations existed. Immunoblotting showed the two anti-core mAbs to be different, one bound only to core which was not substituted with O-antigen, whilst the other bound both to substituted and unsubstituted core. This comparison for monitoring the binding of anti-LPS mAbs demonstrates the potential use of flow cytometry in bacterial cell surface research, and complements results obtained by ELISA and immunoblotting. PMID- 2230141 TI - A method for blocking antigen-independent binding of human IgM to frozen tissue sections when screening human hybridoma antibodies. AB - Using an indirect immunoperoxidase technique antigen independent binding of both human monoclonal and polyclonal IgM was found to a wide range of frozen sections of normal and malignant human glandular epithelia. Identical binding was found using dimeric human IgA (dIgA), whereas no binding was found with monomeric human IgA or human IgG. Secretory component (SC) was found to be the component in these tissues mediating antigen-independent binding of human IgM and dIgA antibodies. A method for the blocking of this antigen-independent binding of human IgM and dIgA was evaluated. Frozen sections of tissues containing SC were blocked with antibody to endogenous immunoglobulin and preincubated with rabbit anti-secretory component antibody (anti-SC) before applying the human monoclonal antibody. This treatment blocked the binding of control polyclonal and monoclonal human IgM to sections of SC-containing tissues such as respiratory and colonic epithelia. The influence of anti-SC on the binding of dIgA could not be established due to interactions between the anti-SC antibody and the IgA preparation. Using this method human hybridoma supernatants containing IgM could be readily screened for reactivity with frozen tissue sections from patients with colo-rectal cancer. This approach is recommended for the screening of human IgM monoclonal antibodies on frozen human tissue sections. PMID- 2230142 TI - An enzyme-linked immunosorbent assay for the measurement of human interleukin-6. AB - An enzyme-linked immunosorbent assay has been developed to measure human interleukin-6. The assay, based on the avidin-biotin amplified two-step sandwich method, is quick (requiring 4.5 h), sensitive (detecting 9.5 pg/ml) and satisfactory in reproducibility and specificity. It shows good correspondence with the results of bioassays, and it is not affected by serum and plasma components. These results indicate that this ELISA is suitable for application to clinical samples, which is a major advantage over the widely used bioassays. PMID- 2230143 TI - A rapid [3H]glycerol radioassay for determination of monocyte-mediated growth inhibition of Mycobacterium avium. AB - [3H]glycerol was used to radiolabel Mycobacterium avium (MA) bacteria after interaction with human monocytes in a rapid in vitro assay for determination of the growth inhibition of the mycobacteria by monocytes. Monocytes and MA were co cultured in 96-well microtiter plates for 1-5 days, and [3H]glycerol was added for an additional 3 days of incubation to radiolabel residual bacteria. The results indicate that monocytes inhibited mycobacterial growth within 24 h of co culture, an activity which increased during incubation until optimal growth inhibition was noted by 3-4 days. A comparison with conventional plate counting methodology demonstrated similar responses between the two assays except that the conventional assay required 2-3 weeks of culture before visible MA colonies could be detected and enumerated. Thus, the development of a rapid radiolabel assay to quantitate the interaction between monocytes and MA will facilitate the investigation of normal host responses to this opportunistic pathogen. PMID- 2230144 TI - Detection of peptide-MHC class II complexes on the surface of intact cells. AB - The interaction of peptides with major histocompatibility complex proteins on the surface of cells is required for their recognition by T lymphocytes. Many studies characterizing the formation of peptide-MHC class II complexes have used either assays for T cell responses or for peptide binding to purified class II molecules. Recently, specific peptide-class II interactions have been demonstrated convincingly on the surface of intact cells. The effects of varying peptide and class II structure have been examined in order to identify structural requirements for binding to cell surface class II molecules and to examine the conformation adopted by immunogenic peptides when bound. PMID- 2230145 TI - Affinity immunoblotting detection of serum monoclonal immunoglobulins reactive with glycosphingolipids. AB - The characterization of serum monoclonal IgM reactive with glycosphingolipid present in the nervous system is of major importance in patients with certain neuropathies. A rapid, sensitive and specific one-step method which permits such a characterization is described. Serum immunoglobulins separated by high resolution agarose electrophoresis are transferred to affinity filters (nitrocellulose sheets coated with glycolipids), and revealed with enzyme-tagged monospecific anti-immunoglobulin antibodies. PMID- 2230146 TI - Murine monoclonal anti-idiotype antibody (alpha) as a probe to detect human monoclonal antibody bound to human tumor tissues. AB - A new immunohistochemical assay was developed for the detection of human monoclonal antibody (HuMAb) bound to human biopsied tumor tissues. A murine anti idiotype monoclonal antibody, alpha type, 18C6 (IgGl), was raised against an IgM HuMAb, L612, defining a tumor-associated ganglioside antigen (GM3) and used as a probe in a three step cell-binding assay (HuMAb + anti-id + biotinylated anti mouse Ig). Anti-id 18C6 has an exclusive binding specificity for HuMAb L612, but does not interfere with the binding of L612 to antigen positive melanoma cell lines or to a purified antigen, GM3. The applicability of 18C6 in the three step cell-binding assay was tested first using a melanoma cell line, UCLASO-M12. L612 bound to M12 cells was specifically detected by 18C6 without any background reactivity in ELISA. When this assay was compared with the standard two-step cell binding assay (HuMAb + peroxidase-conjugated anti-human IgM) using various cultured tumor cell lines, parallel reactivity was observed. The three-step cell binding assay was then applied to various fresh-frozen human tumor sections. Positive reactivity was demonstrated on various histologic types of human tumor tissues: primary melanoma (10/10), metastatic melanoma (4/4), nevus (10/10), lung cancer (3/6), breast cancer (2/6), and colon cancer (1/1). Adjacent normal tissues were unstained. Control experiments included the cell-binding assay with L612 alone, 18C6 alone. L612 + unrelated mouse IgG, and unrelated IgM HuMAb (L72) + 18C6; but biotinylated anti-mouse IgG did not react with these control preparations. The results indicate that anti-id 18C6 is a highly specific probe to assess the expression of the ganglioside antigenic epitope recognized by the L612 HuMAb on biopsied human tumor tissues. PMID- 2230147 TI - Development of technology for linking photosensitizers to a model monoclonal antibody. AB - A procedure is described whereby the photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA) was covalently linked to a model monoclonal antibody in a manner which is reproducible, quantifiable, and retains both the biological activity of the antibody and the cytotoxicity of the photosensitizer. Preliminary steps involved the linkage of BPD-MA to a modified polyvinyl alcohol (PVA) backbone, followed by conjugation to the antibody using heterobifunctional linking technology. Briefly, polyvinyl alcohol (MW ca. 10,000) was modified with 2-fluoro-1-methyl pyridinium toluene-4-sulfonate and 1,6-hexanediamine to produce side chains containing free amino groups. The free carboxyl group of BPD-MA was utilized to conjugate photosensitizer molecules to modified PVA using a standard carbodiimide reaction. Final linkage of the PVA-BPD to a model monoclonal antibody involved further substitution of the carrier with 3-mercaptopropionic acid and carbodiimide to introduce 3-4 sulfhydryl residues per carrier molecule, and introduction of sulfo-m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester residues to the monoclonal (3-4 residues/molecule). Conjugation was effected by reaction of the two species at pH 5.5 for 18 h. Detailed methodology and tests for efficacy of the procedure are provided. PMID- 2230148 TI - Efficient hybridization of mouse-human cell lines by means of hypo-osmolar electrofusion. AB - The fusion of a mouse-human heteromyeloma with a mouse hybridoma is used as a model to define parameters to generate human hybridomas. Electrofusion of these cells in 300 mosM and 75 mosM solutions showed that strong hypo-osmolar conditions resulted in a dramatic increase in the efficiency of hybridoma formation. In contrast to iso-osmolar electrofusion, a high hybrid yield could be obtained by injection of only a single field pulse. The field strength was adjusted in proportion to the increased size of the cells in hypo-osmolar solutions. Hypo-osmolar electrofusion allowed the generation of approximately 0.45% hybrids at a suspension density of 1.75 X 10(5) mouse-human cells/ml corresponding to an input number of 3.5 X 10(4) mouse-human cells. A further increase in the efficiency of hybridoma formation to about 0.6% was achieved by cell alignment in an alternating field of modulated field strength. Experiments in which the total cell number per fusion chamber was decreased at constant optimum suspension density showed that a further increase in the efficiency of hybridoma formation in hypo-osmolar solution was not possible because of the increasing influence of the heterogeneity of the cell lines with decreasing cell number. The results allow the conclusion that hypo-osmolar electrofusion is a potential tool to enhance successful immortalisation of human B lymphocytes. PMID- 2230149 TI - Methods to quantitate human haptoglobin by complexation with hemoglobin. AB - Native human haptoglobin isolated from normal human plasma by affinity chromatography on chicken hemoglobin -Sepharose was used as standard antigen. A direct sandwich ELISA for haptoglobin was developed, with human hemoglobin as a capturing agent. The peroxidase activity of the complex was measured as a means of detecting functional haptoglobin. The reactivities of monoclonal antibody vs. polyclonal antisera on the haptoglobin-hemoglobin complex were compared. Adopting a monoclonal antibody, clone 21.7, which is directed to the alpha chain of haptoglobin, a specific method to quantitate the native haptoglobin which can complex with hemoglobin has been developed. PMID- 2230150 TI - Cytotoxicity assays using cryopreserved target cells pre-labeled with the fluorescent marker europium. AB - We describe a method for standardizing cytotoxicity assays by the use of cryopreserved, fluorescently labeled target cells. The cells are labeled in batches with the fluorogenic element europium (Eu) and frozen in multiple aliquots. Replicate aliquots can be thawed on different days and used for cytotoxicity assays. Thawed pre-labeled cells from the same batch are killed reproducibly, allowing cytotoxicity assays to be standardized. The target cells need only be thawed, washed, counted for viability and used. The availability of pre-labeled, cryopreserved targets facilitates the assessment of cytotoxic activity of individual donors at different times. The method also simplifies the use of large panels of target cell types. By using this procedure it is not necessary to maintain active cultures of target cells, nor is it necessary to use and dispose of radioisotopes. These pre-labeled target cells can be used in various assays where the result is a destroyed target cell such as cell-mediated cytotoxicity, complement mediated cytotoxicity, or antibody-dependent cellular cytotoxicity. PMID- 2230151 TI - A silicon sensor-based filtration immunoassay using biotin-mediated capture. AB - A sensitive sandwich immunoassay for human chorionic gonadotropin (hCG) was developed with biotin-mediated filtration capture and silicon sensor detection. A high density of biotin on the membrane assured efficient capture of complexes containing streptavidin and analyte. Capture efficiency was not affected over a wide range of filtration flow rates or biotin concentrations. The assay utilized the pH sensing ability of the light addressable potentiometric sensor (LAPS) for the detection of urease-antibody conjugates. A LAPS reader was constructed which allowed the enzyme conjugate to be detected in approximately 1 microliter volumes. Effects from variations in detection volume were studied. 10 pg of hCG could be detected in an assay time of 20 min with four standard deviations separation from background. Comparison to a commercial RIA was made. PMID- 2230152 TI - A rapid method for monitoring DNA labelling reactions with haptens. AB - A rapid and simple method for evaluating the efficiency of DNA labelling reactions with haptens is described. The method, called the Flow-Through Hapten DNA Assay (FT-HDA), relies on binding of anti-hapten antibodies/alkaline phosphatase conjugates to hapten-DNA, immobilized on disposable capillary absorbent filters, and visual detection of blue-grey coloured spots appearing on the filter after chromogenic reaction with enzyme substrates. FT-HDA of hapten DNA is markedly faster and simpler than conventional diffusion assays on membranes. PMID- 2230153 TI - Comparison of an enzyme-linked immunosorbent assay (ELISA) with a radioimmunoassay (RIA) for the measurement of rat insulin. AB - A recently developed competitive enzyme-linked immunosorbent assay (ELISA) was compared with a conventional competitive radioimmunoassay (RIA) for the measurement of rat insulin in culture medium. Fifty-six samples were analysed by both assays. There was a correlation coefficient of r = 0.783 between results obtained using the two assay systems. The binding curves of the two assays were differently shaped, so that the ELISA gave good reproducibility over the concentration range 5-50 microU/ml insulin with inter- and intra-assay coefficients of variation less than 14%, but poor reproducibility at higher concentrations. Conversely, the RIA showed excellent reproducibility at concentrations greater than 50 microU/ml insulin, but poor sensitivity and high coefficients of variation below this level. The ELISA procedure offers practical advantages over the RIA, and performs well when measuring physiological concentrations of insulin. PMID- 2230154 TI - Problems in spina bifida in developing countries. PMID- 2230155 TI - Changing criteria of death. PMID- 2230156 TI - Orthopaedic industrial injuries. AB - A study of 600 consecutive cases of industrial injuries, who came from power using mechanised industries at Jaipur was undertaken to determine the incidence, pattern and causes of industrial injuries. The study revealed that there were fewer injuries in the 18 to 25 years age group than in those over the age of 36. Most of the injuries involved the upper limbs (66.2%), of which nearly 41% resulted from entrapment of hands in machines and were serious. This reflected the lack of adequate safety measures where it is most required. PMID- 2230157 TI - Anaerobic bacterial flora of wound sepsis. AB - Two hundred specimens from wound infection (surgical and non-surgical) were cultured for the isolation of anaerobic and aerobic bacteria. Positive cultures were obtained in 174 (87%) and 26(13%) were sterile. Anaerobes were isolated from 31(17.8%), as single culture in 6(3.4%) and as mixed culture with aerobes in 25(14.3%). Amongst anaerobes, anaerobic cocci were predominant (45.9%). Of aerobes Staph pyogenes (35%) was predominant. Metronidazole was the most effective drug against anaerobes and gentamicin against aerobes. No significant difference was noted in antimicrobial susceptibility of anaerobes of surgical and non-surgical wounds. Among aerobes high resistance was observed in surgical wounds. PMID- 2230158 TI - Conservative surgical management of intestinal tuberculosis. AB - Forty-seven proved cases of intestinal tuberculosis admitted to the surgical ward of MKCG Medical College, Berhampur from 1985 to 1987 were subjected to laparotomy. The common pathology found were tubercles over the peritoneum, multiple strictures of intestine, ileocaecal mass, perforation of the intestines, bands and adhesions and mesenteric node involvement. The patients with acute abdomen were operated in emergency and rest as an elective procedure. Conservative surgeries like stricturoplasty, local intestinal resection, perforation closure, by-pass procedures and local ileocaecal resection were done in most of the cases and only in 2 cases right hemicolectomy was done. Biopsy was taken from the viscera, peritoneum and mesenteric nodes. Postoperative mortality was 6.4%, mostly due to toxaemia and fluid and electrolyte imbalance. Postoperative complications in most of the cases were wound infection. All were given a short course of antituberculosis regimen containing INH, rifampicin and ethambutol. Patients were followed up to one year and definite improvement was noted. PMID- 2230159 TI - Course and prognosis of ulcerative colitis. AB - A study of 50 patients (23 males and 27 females) of ulcerative colitis, who were on follow-up showed that maximum number of patients had the disease before the age of 50 years. At the onset, the activity of the disease was severe in 44%, moderate in 32% and mild in 24% of cases. The commonest clinical course of the disease was chronic intermittent type (48%), followed by single attack with subsequent remission (42%). Chronic continuous type was seen in 10% patients only. There was no correlation of the extent of the bowel involvement with the clinical course. The precipitating factors for the onset or reactivation of the disease appeared to be emotional disturbances in 18% and pregnancy in 8%. The complications, both local and systemic, were not frequent. Serious complications like massive haemorrhage, perforation, toxic megacolon and carcinoma colon were not seen at all. PMID- 2230160 TI - Serum leucine aminopeptidase profile in cancers of gastro-intestinal tract with special reference to hepatic metastasis. AB - Serum leucine aminopeptidase (LAP) was estimated in 30 cases of gastro-intestinal cancers, and compared with 50 age and sex matched controls. Highly significant increase of serum LAP was seen in 7 patients with hepatic metastasis (p less than 0.001) from adenocarcinoma of stomach, colon and rectum. The enzyme values showed a highly significant increase in carcinoma of colon, when compared with different anatomical sites of the gastro-intestinal tract (p less than 0.001). However, in adenocarcinoma of stomach and rectum, significantly increased level of serum LAP was observed (p less than 0.01) which contrasted sharply with the normal enzyme values in squamous cell carcinoma of oesophagus and anal canal. PMID- 2230161 TI - Litholapaxy: a fading art. AB - The bladder stones in 45 patients were treated with tactile litholapaxy over a period of 3 years. The overall success rate was 91.1%. The associated urological lesions like enlarged prostate, bladder neck contracture and urethral stricture could be safely dealt with simultaneously with litholapaxy in one sitting which was advantageous to the patient as well as to the surgeon. PMID- 2230162 TI - Occupational hazard of hydrocarbon pneumonitis in fire-eaters. PMID- 2230163 TI - Spontaneous rupture of renal pelvis secondary to ureteric calculous obstruction. PMID- 2230164 TI - Foetal hydantoin syndrome. PMID- 2230165 TI - Genetic counselling. PMID- 2230166 TI - Temporal lobe epilepsy. PMID- 2230167 TI - Brain death and the human organ transplants. PMID- 2230168 TI - Priorities in cardiological practice in a developing country. PMID- 2230170 TI - Spondylosis. PMID- 2230169 TI - Drug epidemic and the GPs. PMID- 2230171 TI - Glucocorticoid therapy for severe Pneumocystis carinii pneumonia. AB - The majority of patients with AIDS and Pneumocystis carinii pneumonia respond to treatment with either high-dose cotrimoxazole or IV pentamidine. Glucocorticoids have been given as 'adjuvant' therapy in those patients who fail to respond to cotrimoxazole or pentamidine. This article discusses the role of glucocorticoids therapy in the treatment of severe Pneumocystis carinii pneumonia and reviews the evidence for their efficacy. PMID- 2230172 TI - Prevalence of cryptosporidiosis in Israeli children with diarrhoea. AB - In a prospective study, Cryptosporidium oocysts were detected in seven (3.25%) immunocompetent children with diarrhoea. The predominant clinical features were watery diarrhoea and vomiting. The patients' mean age was 19 years and infection was more common in late summer-autumn than in the rest of the year. This first survey on cryptosporidiosis in Israeli children has shown a prevalence similar to that observed in other developed countries. PMID- 2230173 TI - A study of three blood culture media for isolating genital mycoplasmas from obstetrical and gynaecological patients. AB - Mycoplasma species are often found colonising the female genital tract. Their ability to become invasive and pathogenic, however, is often ignored, since attempts may not be made to culture these organisms from the bloodstream. We have investigated the ability of three types of blood culture media to support the growth of genital mycoplasmas. The media studied included brain-heart infusion broth, brain-heart infusion broth supplemented with 30% V/V sucrose and fastidious anaerobe broth. Genital mycoplasmas were cultured from the latter medium only. Since this was the sole medium which was liquoid-free, the inhibitory effects of liquoid on Mycoplasma spp. is discussed. This study comprised an investigation of 75 patients in obstetric and gynaecological wards with postpartum or post-operative fever. Genital mycoplasmas were isolated from five (6.7%) patients, four with Ureaplasma urealyticum and one with M. hominis. The value of considering these organisms in the differential diagnosis of fever in 'at risk' patients and of including appropriate media for their isolation is emphasised. PMID- 2230174 TI - Evidence of past delta co-infection with acute hepatitis B in intravenous drug abusers in the west of Scotland. AB - Two hundred sera from asymptomatic hepatitis B surface antigen (HBsAg) negative intravenous drugs abusers (IVDAs) were tested for delta antibody and antiHBc to determine the number of delta co-infections occurring with acute hepatitis B infection in this group. Of the 200 sera, 15 were positive for antidelta and 143 for antiHBc, giving a delta co-infection rate of 10.5%. Laboratory records were consulted to ascertain which IVDAs had acute hepatitis B. Of 29 patients who submitted serum when HBsAg-positive, 10 are currently antidelta-positive. There was no evidence of loss of delta antibody after resolution of acute co-infection. The majority of those with delta co-infection had sought medical attention (10 of 15), whereas only a minority (19 of 128) with only hepatitis B did so. These results suggest that delta co-infection more often results in significant clinical illness than acute hepatitis B alone. PMID- 2230175 TI - Incidence of malaria and efficacy of oral quinine in patients recently infected with human immunodeficiency virus in Kinshasa, Zaire. AB - There is concern that the impaired cell mediated immunity caused by the human immunodeficiency virus may increase the risk of severity of Plasmodium falciparum infection and could lead eventually to a decreased response to standard antimalarial treatment. In 1986, at Mama Yemo Hospital, Kinshasa, Zaire, the incidence of malaria was determined in a cohort of 59 patients who had recently acquired HIV-I infection through blood transfusion and in a cohort of 83 HIV-I seronegative controls who were recipients of HIV-I seronegative blood. All cohort patients were asked to visit the study physician whenever they developed fever. On each of these occasions thick film was examined for the presence of malarial parasites. HIV-I seropositive patients presented more often with episodes of fever per person month observation than HIV-I seronegative patients (P = 0.003). The total number of positive thick films per person months observation was significantly higher among HIV-I seropositive patients than among the HIV-I seronegative ones, but percentages of positive thick films per episode of fever were the same in both groups (46%). During a 5 month period, cohort patients presenting with a moderate attack of malaria were treated with oral quinine 20 mg/kg daily in two doses for 5 days. Twenty-three (92%) of 25 HIV-I seropositive patients and 28 (82%) of 34 HIV-I seronegative patients had a negative film 7 days after starting treatment. This study suggests that there seems to be no direct interaction of major clinical importance between HIV infection and malaria. PMID- 2230176 TI - The value of serum cryptococcal antigen in the diagnosis of cryptococcal infection in patients infected with the human immunodeficiency virus. AB - Serum cryptococcal antigen titres were measured in 828 HIV-infected patients with pyrexia, 69 of whom had meningism. Serum cryptococcal antigen was positive in 17 patients of whom 16 had meningism with cryptococcus isolated from their CSF. The other patient had no meningism, had no evidence of cryptococcal infection on repeated CSF examination and remains well. A positive serum cryptococcal antigen test was therefore valuable in the diagnosis of cryptococcal meningitis, although in all 16 patients meningism was present and a diagnostic lumbar puncture was therefore carried out. In our experience routine screening for serum cryptococcal antigen did not predict patients who subsequently developed cryptococcal meningitis. PMID- 2230178 TI - Infected cephalhaematoma and neonatal osteomyelitis. AB - Neonatal osteomyelitis of the skull secondary to cephalhaematoma has been reported infrequently. The case reported here is that of a 7-week-old infant with a previously resolving cephalhaematoma who presented with cranial osteomyelitis. Cephalhaematomas should be considered potential sites of infection in any infant, even without a history of scalp trauma. PMID- 2230177 TI - False-negative dye-test findings in a case of fatal toxoplasmosis associated with cardiac transplantation. AB - False-negative dye-test results were recorded in a case of fatal toxoplasmosis associated with cardiac transplantation. Serological and histological data require individual consideration in cases of suspected toxoplasma infection of the immunocompromised. PMID- 2230179 TI - Salmonella septic arthritis: a case report and review. AB - We describe a case of septic arthritis in a child with no apparent predisposing conditions. Salmonella virchow was isolated from her knee and faeces, both isolates being identical except for the latter's resistance to ampicillin. Evidence is presented for the acquisition of ampicillin resistance in vivo, including the demonstration of the R plasmid and its ready transferability to Escherichia coli. The recent literature on the subject is reviewed and the role of group CI salmonellae in invasive disease is examined. PMID- 2230180 TI - Ciprofloxacin as a cause of Clostridium difficile-associated diarrhoea in an HIV antibody-positive patient. AB - Ciprofloxacin is an uncommon cause of pseudomembranous colitis. A case is described in which diarrhoea was associated with the presence of clostridial toxin in an HIV-infected patient and the possible implications are discussed. PMID- 2230181 TI - Infective endocarditis caused by Streptococcus suis serotype 2. AB - Infective endocarditis caused by Streptococcus suis serotype 2 is not uncommon in pigs but is rare in human beings. We describe the case of a pig-farmer with endocarditis due to S. suis serotype 2 and in whom prolapse of the mitral valve was the predisposing cardiac lesion. Streptococcus suis, a possible cause of infective endocarditis in endemic areas, may be confused with other group D streptococci. In suspected cases a history of contact with pigs or raw pork should be sought. PMID- 2230182 TI - Public Health Laboratory Service surveillance of prophylaxis by specific hepatitis B immunoglobulin in England and Wales during the period 1975-1987. AB - Surveillance of specific hepatitis B prophylaxis given after accidental or sexual exposure was continued throughout the period 1975-1987 by keeping records of exposures and ascertaining acute attacks of hepatitis B by postal enquiry. Acute hepatitis B developed in 53 (0.6%) of 9370 recipients of prophylaxis; the highest rate (3.7%) was among 564 sexually exposed, 0.9% among 2056 accidentally inoculated and 0.2% among 5747 persons who had other skin or minor exposures affecting the mucous membranes. There were no cases among 1003 recipients whose exposures did not meet the criteria for prophylaxis. None of the 53 patients died and only one of the 44, for whom sickness records were completed, reported a severe attack. Comparisons of six attacks among 623 who had inoculation injuries with material tested for hepatitis 'e' antigen and antibody gave no indication of better protection by early prophylaxis or by a two-dose schedule. PMID- 2230183 TI - Imported melioidosis in a British native. PMID- 2230184 TI - Prophylaxis for contacts of melioidosis. PMID- 2230185 TI - Inhibitory effect of fetal calf serum on the growth of Haemophilus ducreyi. PMID- 2230186 TI - Latent HIV infection following a low degree of exposure and the importance of repeated western blot. PMID- 2230187 TI - [Neuralgia of the pudendal nerve. Anatomo-clinical considerations and therapeutical approach]. AB - The anatomic study of the pudendal nerve and its relation allows an approach of the mechanisms of compression likely to engender perineal neuralgia. Two conflictual zones are isolated: the first is linked to the clamp which is produced by the insertion of the sacro-epinous ligament on the ischial spine and the sacro-tuberal ligament; the second is linked to the falciform process of the sacrotuberal which threatens the nerve by its sharp upper edge. This conflict is particularly acute in a sitting position. The relation between the trunk of the nerve, its branches and these zones of conflict may explain the clinical observations. The electrophysiological investigations (detection of neurogenic muscles of the perineal floor. Increased sacral latency, pudendal nerve terminal motor latency) confirm the diagnosis. The anesthetic blocks of the pudendal nerve on the ischial spine only have a complimentary diagnostic value. The peridural blocks may also have an interesting therapeutic action (60% of good results 3 months later). In some persistent cases, the nerve has been decompressed firstly by perineal approach, but latterly by transguteal approach. PMID- 2230188 TI - [Echoguided renal needle biopsy. Technique and results. Report of 413 examinations]. AB - Blindly executed for a long period with only X- Ray detection, renal biopsy benefits nowadays of precision and security of real-time echoguiding. The authors describe their technique without bondage between needle and transducer and comment their results about 413 examinations. PMID- 2230189 TI - [Cystinic lithiasis. Current aspects of the urologic treatment]. AB - On the basis of a series of 9 patients (12 renal units) gathered over 19 years, the authors analyze the current possibilities of treatment of cystine lithiasis. They first describe the characteristics of this litiasis, which is rare but serious, being naturally prone to recurrence because it is caused by a genetic defect. The development of extracorporeal lithotripsy raised great hopes for the treatment of this lithiasis, but it was soon realized that cystine strones were hard to break. However, even the mere fragmentation of the stones improves the dissolving action of the various drugs proposed to modify the pH of urine. The authors consider that open surgery by means of posterior vertical lumbar section still is indicated for larger stones, and percutaneous nephrolithotomy seems to be a very useful technique, either exclusively or as a complement of extracorporeal lithotrity. PMID- 2230190 TI - [Urothelial bladder tumors in stage pTa. I.--What is the risk for the patient?]. AB - We present 534 superficial (pTa) bladder cancer, followed in our institution between 1970 et 1990. During the "follow up" period, 20 patients (4%) died of their cancer, 64 patients (12%) presented an "infiltrative" recurrence and 338 (63%) one or more "superficial" recurrence. PMID- 2230191 TI - [Our experience of spinal anesthesia for transurethral resection of the bladder and prostate. Retrospective study of 334 patients operated in 1986]. AB - Retrospective study of one years is performed on 334 patients who undergo transurethral surgery. Spinal anesthesia is used in 263 cases, general anesthesia in 71. Spinal administration of local anesthetics (lidocaine hyperbaric 5% or bupivacaine 0.5%) or opioid (Pethidine 1 mg/kg) have been used in old patients without any complication. The advantages are less blood uses, early stand up, no discontinuity in oral nutrition. For our team there are only few contra indications for spinal anesthesia: blood coagulation abnormalities or some very rare heart diseases. PMID- 2230192 TI - [Urodynamic consequences of urethral stenosis. Hydrodynamic study with a theoretical model]. AB - An urethral model was designed to assess the hydrodynamic consequences of stenosis of the bulbar urethra. This model was based on the geometric and hydrodynamic analysis of micturing urethrograms in a patient whose maximum flow rate was 24 ml/s for a bladder pressure of 40 cm of water. It corresponds to the conditions of flow observed wit maximum bladder pressure and flow rate. During this short period, the shape of the urethra is regarded as stable. Calculation took account of the characteristics of a turbulent flow of urine, of the head loss due to friction of the urine on the walls and of the head loss caused by the geometrical changes of the urethra from the neck of the bladder to the meatus. In these conditions, applying Bernouilli's equation allowed plotting of bladder pressure for various levels of urethral resistance. If there is no stenosis, the theoretical maximum flow rate of the model with a bladder pressure of 40 to 80 cm of water should be 19 to 26 ml/s. Calculation showed that a sudden reduction of the diameter to less than 2.5 mm occurring in a segment of the urethra with a diameter of 4 mm accounts for a flox rate lower than 15 ml/s, except when bladder pressure can exceed 100 cm of water. The decrease in the maximum flow rate caused by urethral stenosis is all the greater as bladder pressure remains low or normal, with other causes of head loss or with associated upstream dilatation. Lastly, progressive narrowing leads to a smaller head loss and will therefore be better tolerated than sudden narrowing to the same caliber. Inversely, a long stenosis will be less well tolerated as the head loss due to friction in a long and narrow passage is increased. The diameter of a stenosis accounting for a maximum flow rate of less than 15 ml/s cannot be determined in the absolute. Analyzing the hydrodynamic consequences of stenosis also requires knowing the associated urodynamic and geometric parameters. PMID- 2230193 TI - [Prevention of complications in inguinal lymphadenectomy]. AB - Inguinal lymphadenectomy, as indicated in the treatment of metastases of carcinoma of the penis and of malignant melanoma in the inguinal lymph nodes, involves considerable mortality and morbidity. From February, 1988, to January, 1990, we performed 15 inguinal lymphadenectomies in 10 patients with an average age 51.9 +/- 5.3 years. The technique used combined a transverse incision parallel to the inguinal fold, complete inguinal lymphadenectomy, transposition of the sartorius muscle and vaporization of a film of fibrin glue. The last 2 operations, besides the effectives protection of the femoral pedicle, aim at suppressing dead spaces that may produce hematomas, subcutaneous infection or lymphoceles, and at avoiding the insertion of an aspiration drain, which causes persistent lymphorrhea. Out of the 15 cases of lymphadenectomy, 5 presented with a small- (48 ml in average) or medium-volume (200 ml) lymphocele, which was treated by a simple evacuating puncture. No necrosis of the skin edges, subcutaneous infection or lymphorrhea were observed. These results are encouraging, since our patients can rapidly resume their social life and have an acceptable quality of survival. PMID- 2230194 TI - Treatment of distal hypospadias. Comments about the MAGPI procedure. PMID- 2230195 TI - [Value of a scrotal myocutaneous flap in the repair of penile and urethral skin loss]. AB - The authors report a case of a large penile skin and urethral defect repair using a scrotal myocutaneous flap. The modalities, advantages and defects of the method were detailed. This technique permitted to obtain a very satisfactory result. Then we extended it to the failures of the hypospadias and epispadias reconstruction. PMID- 2230196 TI - Psoriasis workshop: molecular, immunologic and pharmacologic aspects of psoriasis. Deer Valley, Utah, September 14-17, 1989. Proceedings. PMID- 2230197 TI - Epidermal growth factor/transforming growth factor alpha receptors and psoriasis. AB - The abnormal growth and differentiation in psoriasis is reflected in the abnormal regulation of Epidermal Growth Factor/Transforming Growth Factor Alpha (EGF/TGF alpha) receptor metabolism. In psoriasis and other hyperproliferative skin conditions these receptors are persistently expressed throughout the interfollicular epidermis as long as the growth stimulatory signal persists. One of the first biochemical signs of effective therapy of psoriasis is the return of the EGF/TGF alpha receptor pattern toward the primarily basilar distribution seen in normal human adult skin. Whether the abnormal expression of TGF alpha in the involved skin induces the persistent expression of EGF receptors is not known nor is the signal that causes the increased production of TGF alpha. Studies to determine what factors regulate EGF receptor expression and TGF alpha induction may yield important new insights into the pathogenesis and therapy of psoriasis. PMID- 2230198 TI - Immunologic mechanisms in psoriasis. AB - The demonstration of activated T lymphocytes, HLA-DR+, I-CAM1+, gamma IP-10+ keratinocytes, and increased levels of lymphokines in active plaques suggests that immunologic mechanisms may play a role in the pathogenesis of psoriasis. Epidermal hyperplasia and inflammation in psoriasis may be linked by those cytokines many of which are produced by both keratinocytes and leukocytes. Epidermal acanthosis and keratinocyte mitoses have been observed in delayed-type hypersensitivity reactions and after the intradermal injection of gamma interferon. Gamma interferon and its induced proteins have been demonstrated in active psoriatic plaques. Increased levels of the keratinocyte autocrine cytokines, transforming growth factor (TGF)-alpha and interleukin (IL)-6, have been detected in active plaques. The apparent overexpression of IL-6 in hyperplastic psoriatic tissue may explain features of psoriasis that link keratinocyte proliferation with immune activation and tissue inflammation. Both IL-6 and gamma interferon increased TGF-alpha expression in normal cultured keratinocytes. Cytokines produced during immune activation and other inflammatory processes may lead to epidermal hyperplasia. PMID- 2230199 TI - Psoriasis vulgaris: a genetic approach. AB - Evidence for a genetic contribution in psoriasis comes from direct examination of a large segment of the population in an isolated island environment, epidemiologic and questionnaire studies presented to psoriatic patients, twin studies collected from the literature and from twin registries, and splitsibship analysis. The concordance of psoriasis in monozygotic twins was 65-72%, whereas psoriasis in dizygotic twins was 15-30%. Determination of concordance in older twin pairs from a national twin registry in Denmark revealed nearly 90-100% heritability. In order to link psoriasis with known markers within the human genome, serologic studies have been carried out with a variety of blood group and polymorphic protein antigens. A weak association with the MNS and Lewis Blood Groups Systems (relative risk, 3.5) has been identified. Stronger associations with class I B locus and class II D locus genes (relative risk, 8-12) have also been determined by studies of the human lymphocyte-antigen system. Finally, a strong association with HLA Cw6 has been determined; this marker is thought to be in linkage disequilibrium with B and D locus genes previously associated with psoriasis. The relative risk of developing psoriasis in HLA Cw6 positive individuals is about 24. A few large kindred have been reported in the dermatology literature. These support the hypothesis of autosomal dominant inheritance with penetrance of approximately 60%. In cooperation with The National Psoriasis Foundation, we have now identified over 90 families with psoriasis in three generations. We have begun the process of ascertainment, the construction of family trees, and the collection of leukocyte DNA for linkage analysis with established restriction fragment polymorphisms (RFLP). Our initial assessment is being directed to four RFLP that span approximately 30 centiMorgans of the short arm of human chromosome 6. Although karyotyping is uncommonly done in patients because of psoriasis, we now seek evidence of translocations of chromosome 6 in association with psoriasis. PMID- 2230200 TI - Speculations on the immunopathogenesis of psoriasis: T-cell violation of a keratinocyte sphere of influence. AB - The thesis is advanced that the differences in antigen processing and presentation described for "fresh" and "cultured" Langerhans cells in vitro reflect similar differences between intraepidermal and intranodal Langerhans cells in vivo. The functional properties of Langerhans cells are dependent upon the microenvironment in which they reside; thus, intraepidermal Langerhans cells are under the influence of cytokines secreted by keratinocytes, whereas intranodal Langerhans cells come under the influence of lymphokines from T lymphocytes. It is speculated that a genetic lesion in psoriasis robs keratinocytes of their capacity to create an "appropriate" epidermal microenvironment. As a consequence, intraepidermal Langerhans cells adopt the functional program of intranodal cells. When "uninvolved" psoriatic skin receives a cutaneous challenge with antigen, Langerhans cells, by activating naive T cells in situ, unwittingly engender a microenvironment that is more appropriate to a lymph node. This skin becomes "involved" as it gradually acquires features associated with lymph nodes (such as high endothelial venules). And the derangement is further complicated by abnormalities of proliferation and differentiation among keratinocytes and dermal fibroblasts as they respond to the inappropriate T-cell-derived lymphokines, giving rising to the typical, active psoriatic lesion. PMID- 2230201 TI - Lymphocyte chemoattractants in psoriasis and normal skin. AB - The local production of lymphocyte attractants may influence both physiologic lymphocyte trafficking in the skin as well as the infiltration of these cells in pathologic states. Recent evidence for the production of acidic lipid lymphocyte chemoattractants, particularly 12[R]-hydroxyeicosatetraenoic acid, in psoriatic lesions is reviewed. Water extractable lymphocyte attractant activity may also be recovered from both normal skin samples and psoriatic lesional stratum corneum, and may be important in the pathophysiology of lymphocyte trafficking. Less than 10 kD activity from normal skin has undergone the most detailed characterization. This has led to the isolation of a novel, as yet unidentified compound from normal skin, which we have termed "plasma-associated lymphocyte chemoattractant" (PALC). PMID- 2230202 TI - Interleukin-1 in human skin: dysregulation in psoriasis. AB - Cytokine dysregulation is an attractive concept to explain many of the observed abnormalities in psoriasis. IL-1, in particular, can potentiate immune cellular activation, activate fibroblasts, and increase endothelial cell adhesiveness to leukocytes. Here, we review IL-1 regulation in normal and psoriatic skin in vivo in relation to normal skin and cultured keratinocytes. Contrary to expectations, IL-1 functional activity in psoriatic lesions is reduced, not increased, relative to normal skin. The reduction is attributable to the presence of IL-1 inhibitors, reduced IL-1 alpha levels, and an IL-1 beta that lacked function in T-cell assays. IL-1 beta protein is actually significantly increased in psoriatic lesions, but the mechanism of its non-functionality remains unclear. Unlike cultured keratinocytes, which accumulate large, inactive IL-1 beta precursors, both normal and psoriatic skin process IL-1 beta to a mature form. Novel mechanisms of post-translational processing by epidermis in vivo may generate a novel form of IL-1 beta with unknown functions. The marked abnormalities of IL-1 regulation in psoriatic skin suggest that this molecule may be important in normal skin homeostasis. PMID- 2230203 TI - The role of epidermal cytokines in inflammatory skin diseases. AB - Cytokines (hormone-like polypeptide mediators) play a major role in inflammatory and immunoregulatory responses. Skin, and particularly keratinocytes in the skin, represent a potent source for many cytokines, including interleukins 1, 6, 8, and the hemopoietic colony stimulating factors. Cytokines initiate their biologic action by interacting with target cells bearing cytokine receptors and then initiating a cascade of cellular interactions. Certain inflammatory skin diseases have been associated with overproduction of cytokines, alteration in cytokine receptors, or dysregulation of cytokines. While data is still quite preliminary, it is likely that cytokines contribute to the pathogenesis of many inflammatory skin diseases. PMID- 2230204 TI - Lymphocyte adhesion to psoriatic dermal endothelium: mechanism and modulation. AB - Psoriasis is characterized by the hyperproliferation of keratinocytes in the epidermis and the accumulation of activated CD4+ T lymphocytes in the upper dermis. We have recently tested the hypothesis that the abnormal endothelial proliferation in the dermal papillae of psoriatic lesions may be mechanistically linked to the expression of endothelial ligands capable of promoting lymphocytes binding and extravasation. The results indicated that specialized endothelial cells lining the post-capillary venules of psoriatic lesions are capable of promoting the selective adherence of human CD4+ T cells and its memory subset. In contrast, B cells, CD8+ T cells, and CD45RA+ T cells are deficient in their capacities to bind. The adhesion process is energy and calcium dependent and involves tissue-specific lymphocyte receptors, with LFA-1 molecules playing an accessory role. We concluded that transformation of the dermal endothelium into a lymphocyte-receptive phenotype by defined growth factors or cytokines may represent a positive feedback mechanism promoting lymphocyte migration into the diseased sites. PMID- 2230205 TI - The role of the immune system in the pathogenesis of psoriasis. AB - Psoriatic involved skin contains an increased number of activated T cells. The mechanism through which these T cells achieve and maintain their activated state is unknown, and both antigen-dependent and -independent mechanisms may contribute. Recently a novel pathway of antigen-independent T-cell activation has been described. This pathway is identified by a monoclonal antibody that binds to a T-cell membrane surface molecule termed "UM4D4.". This molecule is expressed on a minority (20%) of psoriatic peripheral blood T cells but on a majority (75%) of the T cells in lesional skin. Thus, UM4D4 could play a role in antigen independent T-cell activation in psoriasis. Indeed the monoclonal antibody anti UM4D4 consistently induces proliferation of psoriatic UM4D4+ T-cell clones. The activity of antigen-dependent pathways are also enhanced in psoriatic epidermis in as much as involved skin relative to uninvolved skin contains an increased number and function of antigen-presenting cells. Upon activation, the lesional T cells release lymphokines. Central to the immune hypothesis of psoriasis is that some of these T-cell lymphokines act on keratinocytes to induce changes characteristic of psoriasis. Indeed lymphokines from lesional psoriatic T-cell clones directly alter in vitro keratinocyte phenotype through induction of intercellular adhesion molecule-1 (ICAM-1) and HLA-DR cell-surface expression. Furthermore, the lymphokines also enhance keratinocyte growth. These data suggest a critical role for the immune system in the pathogenesis of psoriasis. PMID- 2230206 TI - Lymphocyte trafficking in psoriasis: a new perspective emphasizing the dermal dendrocyte with active dermal recruitment mediated via endothelial cells followed by intra-epidermal T-cell activation. AB - Prominent within the inflammatory infiltrate of psoriasis are HLA-DR positive T lymphocytes and factor XIIIa positive dermal dendrocytes. Many investigators studying psoriasis have assumed that the HLA-DR positive T cells are activated, and thereby capable of producing lymphokines such as gamma interferon. However, by immunohistochemical analysis, greater than 95% of the dermal T cells in psoriatic lesions are Ki-67 negative, which suggests that they are in a resting or non-cycling (Go) state. In contrast to the dermal T-cell population, the epidermal T-cell population contains a greater population of Ki-67 positive lymphocytes. The entry of the T cells into the epidermis is, therefore, apparently associated with an important activation event, which in all likelihood involves interaction with the keratinocyte. The presence of activated intraepidermal T cells has been substantiated by the ability to detect gamma interferon mRNA by polymerase chain reaction in epidermal sheets of psoriatic lesions. The pathophysiologic implication in psoriasis for these distinctions and compartmentalization involving dermal and epidermal T cells are placed into the context of a cascade of cellular trafficking events, which are further dissected into a specific network of molecular mediators of inflammation. This report suggests that more attention should be placed on the microenvironment of the skin, with specific emphasis on the mechanism by which T cells accumulate in the dermis and epidermis, and elucidation of the selective inductive and recruitment capabilities of endothelial cells, perivascular dermal dendrocytes, and keratinocytes. PMID- 2230207 TI - Immunology of AIDS related to psoriasis. AB - The association of severe psoriasis with HIV infection, which dysregulates and destroys the human immune system, supports the hypothesis that psoriasis is an immunologically mediated disease. Psoriasis and Kaposi's sarcoma share angiogenesis as basic early findings and could both be caused by differential cytokine expression or responsiveness. AIDS and research models including transgenic mice offer new models in which to study the role of the immune system and specific gene products in the pathogenesis of psoriasis and other skin diseases. PMID- 2230208 TI - The expression of retrovirus-like particles in psoriasis. AB - Retrovirus-like particles have been isolated from patients with psoriasis. Antigens crossreacting with the major internal protein, pso p27, of these particles have been demonstrated in the wall of dermal vessels and in a subfraction of cells in psoriatic lesions. The antigen has also been observed in blood lymphocytes from psoriatic patients. Pso p27 antigen and anti-pso p27 antibodies are present as complement-activating immune complexes in psoriatic scale and in the blood of patients with psoriasis and psoriatic arthritis. The potential contribution of the circulating immune complexes to the inflammatory process in psoriasis is discussed. PMID- 2230209 TI - Multi-stage program of differentiation in human epidermal keratinocytes: regulation by retinoids. AB - The proliferation and differentiation of epidermal keratinocytes in vivo and in vitro is influenced by a variety of different factors, including several peptide growth factors, protein kinase C activators, retinoids, and various cytokines. Retinoids can affect the proliferation of human epidermal keratinocytes either positively or negatively and influence the multi-step program of differentiation in epidermal keratinocytes at very specific stages. Epidermal keratinocytes express nuclear retinoic acid receptors, RAR alpha, and RAR gamma. It is likely that at least some of the alterations in gene expression induced by retinoids are mediated through these RAR. The cytosolic retinoic acid-binding protein (CRABP), which is differentially expressed during squamous differentiation of human epidermal keratinocytes, may control the effective concentration of retinoic acid in the cell and therefore regulate indirectly gene expression. PMID- 2230210 TI - Metabolism of natural retinoids in psoriatic epidermis. PMID- 2230211 TI - Cytotoxic and immunologic effects of methotrexate in psoriasis. AB - Based on recent experience that Cyclosporin A, an immunosuppressive drug, produces marked improvement in psoriasis, possible immunomodulatory activities of methotrexate (MTX) have been reviewed to look for alternate mechanisms of MTX action in psoriasis. It is generally considered that the therapeutic results of MTX in psoriasis are related to a direct effect on epidermal cell hyperplasia through inhibition of DNA synthesis. Several studies in the literature now suggest possible effects of MTX on the immune system of psoriatics as well as in animal models that may have some pathogenic similarities to psoriasis. In psoriatics receiving MTX, neutrophil chemotaxis is suppressed, resulting in a possible alteration in the potential pathologic activity of neutrophils commonly found in lesional skin. MTX does improve both psoriatic and rheumatoid arthritis. Animal studies of the latter using adjuvant arthritis and graft vs host disease (GVHD) have indicated several possible mechanisms for MTX that affect these processes. In GVHD, MTX selectively destroys cycling CD8+ cells, and in adjuvant arthritis the activation of macrophages is prevented by inhibition of T-cell function. While MTX generally has not been clinically utilized as an immunomodulatory drug for immunologically related diseases, it may, nonetheless, have selective actions that could be specific for some diseases. MTX and Cyclosporin A could work mechanistically in similar ways but at different steps in the activation of T cells and macrophages. It may be that the major direct effect of MTX on epidermal cell proliferation is complemented or even mediated by subtle immunoregulatory effects on the melange of cells in the affected skin and the systemic immune response. PMID- 2230212 TI - Excision repair of pyrimidine dimers induced by simulated solar radiation in the skin of patients with basal cell carcinoma. AB - One prominent lesion induced in DNA by ultraviolet (UV) radiation is the cyclobutyl pyrimidine dimer formed between adjacent pyrimidines on the same DNA strand. We investigated whether people who have developed basal cell carcinoma on sun-exposed skin have an altered ability to repair UV-induced pyrimidine dimers in DNA. Twenty-two patients with at least one basal cell carcinoma, aged 31-84 years, and 19 healthy volunteers, aged 25-61 years, took part in the study. Both groups were given one minimal erythema dose (MED) of simulated solar radiation on the lower back. DNA was extracted from the irradiated skin 0 to 6 h later, and the number of UV-induced pyrimidine dimers was determined using a dimer-specific endonuclease. At time 0, the average number of dimers per unit of DNA was similar in the two groups. After 6 h, an average of 22 +/- 4% of the dimers were removed in the group with basal cell carcinoma compared to 33 +/- 4% in the cancer-free group. In the basal cell carcinoma group, only 23% of the patients repaired more than 30% of the dimers after 6 h, compared with 53% of the cancer-free subjects (p less than 0.05). We conclude that patients who develop basal cell carcinoma on sun-exposed skin may have a decreased ability to repair pyrimidine dimers induced in skin exposed to simulated solar radiation. PMID- 2230213 TI - Reversal effects of topical retinoic acid on the skin of kidney transplant recipients under systemic corticotherapy. AB - The systemic long-term corticosteroid treatment administered to kidney graft recipients (KGR) within the framework of the required immunosuppressive therapy induces an atrophy of the skin, from the sixth month onwards. We studied the effect of topical all-trans retinoic acid (0.05%; Galderma Labs.) applied to the forearms of 27 KGR (14 men, 13 women) over a 6-month period. Twenty-four subjects completed the trial. The following results were obtained in the treated forearm versus the untreated forearm (excipient alone): clinically, an increase in skin thickness; by noninvasive techniques, an increase in skin thickness, skin elasticity, skin conductance, and TEWL, and a reduction in the size of the corneocytes. No change in stratum corneum lipid content was observed. A sex related difference was noted in the response to treatment under our experimental conditions, the female patients responding better. A punch biopsy (4 mm) was performed on both forearms of four patients after the 6-month period. Histologic and ultrastructural examination revealed epidermal and dermal changes evoking increased cellular metabolism in the retinoic acid-treated forearms. PMID- 2230214 TI - Percutaneous retinoid absorption and embryotoxicity. AB - A single application of 17 micrograms/kg or 8.7 mg/kg all-trans-[10,11-3H2] retinoic acid dissolved in acetone to shaved dorsal hamster skin resulted in rapid absorption and dose-dependent rates of elimination. An equation describing a two-compartment open model with a very brief lag time and first-order uptake and elimination was used to describe the central plasma compartment kinetics. Unchanged all-trans-retinoic acid represented less than or equal to 4% of the total circulating radio-activity. Peak circulating concentrations of parent all trans-retinoic acid were less than those observed after an equivalent oral dose, but prolonged absorption from the skin appears to contribute to high total bioavailability of topical retinoid. Topical administration to intact skin of up to three consecutive doses of 10.5 mg/kg/d all-trans-retinoic acid or a single 5 mg/kg dose of etretinate (Ro 10-9359) during a critical stage of embryogenesis in hamsters caused erythema and/or dose-dependent epidermal hyperplasia at the site of application, but failed to induce a significant teratogenic response. Topical application of 0.01-1.0 mg/kg arotinoid Ro 13-6298 resulted in dose-dependent mucocutaneous toxicity and an increase in the numbers of dead embryos and malformed offspring. The marked skin toxicity and attenuated concentrations in maternal blood, compared to the oral route, limit the amounts of retinoid that can reach the hamster embryo. It is thus more important to compare the retinoid systemic values (absorbed dose) than it is to compare the oral or topical (applied) dose, when interpreting the results of conventional teratogenicity bioassays. The data suggest that in the human it is skin toxicity that limits the amounts of retinoid that can be applied and subsequently reach the embryo. In the rodent, overt skin toxicity under continued dosing could increase the amounts of retinoid penetrating the skin and reaching the embryo. PMID- 2230215 TI - Cyclosporine A in the treatment of psoriasis: a clinical and mechanistic perspective. AB - Cyclosporine A, a unique immunomodulatory agent, has been used increasingly over the last 5 years in the management of severe psoriasis. The remarkable efficacy of this drug coupled with its known immunosuppressive properties have enabled a further appreciation of the role of the immune system in the induction and maintenance of psoriatic plaques. Although acting primarily on T lymphocytes, there is also evidence for an effect of cyclosporine A on other constitutive cell types within the skin. The future use of systemically administered cyclosporine A in the treatment of psoriasis and other cutaneous diseases is dependent on the successful balance of efficacy and side-effect profile; namely, the dose-related problems of hypertension and nephrotoxicity. As a result of the toxicity encountered with systemically administered cyclosporine A, attempts to formulate a successful topical preparation for use in cutaneous disease are being made. The advent of cyclosporine A provides the dermatologist with a new therapeutic strategem in the management of psoriasis, although the long-term safety of such interventional therapy remains to be discerned. PMID- 2230216 TI - Susceptibility to effects of UVB radiation on induction of contact hypersensitivity as a risk factor for skin cancer in humans. AB - Normal, healthy human volunteers and patients with proved history of non-melanoma skin cancer have been tested for their capacity to develop contact hypersensitivity to dinitrochlorobenzene (DNCB) following exposure of buttock skin to acute, low-dose ultraviolet B (UVB) radiation. Using a radiation protocol that achieves virtually complete depletion of normal-appearing Langerhans cells from irradiated skin, it was learned that approximately 60% of healthy volunteers developed vigorous contact hypersensitivity (CH) when 2000 micrograms DNCB was painted on the irradiated site. These individuals were designated UVB-resistant, and were distinguished from other individuals, designated UVB-susceptible, who failed to develop contact hypersensitivity following an identical treatment protocol. It was then discovered that virtually all (92%) skin cancer patients exposed to UVB and DNCB failed to develop CH, i.e., were UVB-susceptible. In subsequent experiments, epicutaneous application of 2000 micrograms DNCB to unirradiated skin of UVB-susceptible individuals revealed a further distinction between normal persons and skin cancer patients. Approximately 45% of the latter (and none of the former) remained unresponsive (failed to develop contact hypersensitivity following this second attempt at sensitization), implying that they had been rendered immunologically tolerant. These tolerant individuals responded normally to the unrelated hapten, diphencyprone. We conclude that human beings resemble inbred strains of laboratory mice in that some individuals are UVB-susceptible, whereas others are UVB-resistant. Because the incidence of UVB susceptibility was significantly higher in skin cancer patients, and as specific unresponsiveness could be demonstrated only in these patients, we propose that UVB-susceptibility, as we define it in this hapten system, may be a risk factor for the development of skin cancer. PMID- 2230217 TI - Sodium lauryl sulphate for irritant patch testing--a dose-response study using bioengineering methods for determination of skin irritation. AB - The dose-response relationship in patch testing with sodium lauryl sulphate (SLS) was studied. The irritant skin response was quantified by visual scoring as well as by the following noninvasive methods: measurement of transepidermal water loss (TEWL) by an evaporimeter, measurement of skin color by a colorimeter, measurement of superficial blood flow by laser Doppler flowmetry, and measurement of edema in the skin by ultrasound A-scan. Twelve volunteers were patch tested with 0.12, 0.25, 0.50, and 1.00% SLS, and the skin response was evaluated after 24 and 48 h, respectively. We found a statistically significant linear dose response relationship between dose of SLS and skin response evaluated by measurement of TEWL, skin color, superficial blood flow, and edema. Statistical evaluation by regression analysis proved measurement of TEWL to be the method best suited overall for quantification in relation to patch testing with SLS, whereas colorimetry was found to be the least sensitive of the applied methods. Ultrasound A-scan was found to be a promising method for quantification of the inflammatory response, being consistently more sensitive than measurement of skin color. PMID- 2230218 TI - Minoxidil sulfate is the active metabolite that stimulates hair follicles. AB - An important step in understanding minoxidil's mechanism of action on hair follicles was to determine the drug's active form. We used organ-cultured vibrissa follicles to test whether it is minoxidil or its sulfated metabolite, minoxidil sulfate, that stimulates hair growth. Follicles from neonatal mice were cultured with or without drugs and effects were assessed by measuring incorporation of radiolabeled cysteine in hair shafts of the treated follicles. Assays of minoxidil sulfotransferase activity indicated that vibrissae follicles metabolize minoxidil to minoxidil sulfate. Dose-response studies showed that minoxidil sulfate is 14 times more potent than minoxidil in stimulating cysteine incorporation in cultured follicles. Three drugs that block production of intrafollicular minoxidil sulfate were tested for their effects on drug-induced hair growth. Diethylcarbamazine proved to be a noncompetitive inhibitor of sulfotransferase and prevented hair growth stimulation by minoxidil but not by minoxidil sulfate. Inhibiting the formation of intracellular PAPS with chlorate also blocked the action of minoxidil but not of minoxidil sulfate. Acetaminophen, a potent sulfate scavenger blocked cysteine incorporation by minoxidil. It also blocked follicular stimulation by minoxidil sulfate apparently by directly removing the sulfate from the drug. Experiments with U-51,607, a potent minoxidil analog that also forms a sulfated metabolite, showed that its activity was inhibited by both chlorate and diethylcarbamazine. These studies show that sulfation is a critical step for hair-growth effects of minoxidil and that it is the sulfated metabolite that directly affects hair follicles. PMID- 2230219 TI - Experimental models for psoriasis. AB - Evidence suggests that inherent in skin of psoriatic subjects are cells, architectural structures, and/or mediators, which are, at a minimum, responsible for its hyperproliferative epidermis. An objective of our laboratory has been to establish an in vitro definition of this inherent aberration. Fibroblasts are important to epidermal proliferation/differentiation. This, and an unconfirmed report that fibroblasts from psoriatic subjects might drive the abnormal epidermal proliferation in psoriasis, have caused further focus on the fibroblast. Data show that fibroblasts from patients with psoriasis, both involved and uninvolved, in the presence of human serum, either normal or psoriatic, have an increased rate of proliferation. Fibroblasts from uninvolved psoriatic sites are most responsive. To determine if fibroblasts from psoriatics could induce the psoriasiform phenotype on normal keratinocytes, an interactive skin equivalent system has been developed. With this system, fibroblasts from uninvolved and involved sites cause normal keratinocytes to have an enhanced outgrowth. Uninvolved fibroblasts cause the greatest changes. The nature of the skin equivalent system calls for this to occur via message over distance. We conclude that fibroblasts from psoriatic subjects can induce a psoriasiform phenotype via a soluble message. PMID- 2230220 TI - Production of paf-acether by human epidermal cells. AB - The production of the inflammatory mediator paf-acether (paf) from human epidermal cells was investigated in vitro. Human epidermal cells, freshly isolated from normal skin or in culture, were incubated in Tyrode's buffer containing 0.25% lipid-free bovine serum albumin in the presence of 2 microM calcium ionophore A23187, at 37 degrees C, for 1 to 60 min. Paf production slightly began at the first min of stimulation, was significant after 10 min, reached a maximum at 20 min (251 +/- 25 pg/l X 10(6) cells, mean +/- 1 SD), and decreased thereafter. About 50% of the paf amount produced by epidermal cells was recovered in supernatants. Addition of the non-acetylated paf precursor 1-O octadecyl-sn-glycero-3-phosphocholine, i.e., lyso-paf, at 0.1 microM to epidermal cells during A23187-stimulation did not alter this production. In contrast, addition of acetyl-coenzyme A at 0.1 mM enhanced paf production by 5 times. The material produced by epidermal cells was identical to synthetic paf because: 1) the aggregation of aspirin-treated and ADP-insensitive washed rabbit platelets it induced was inhibited by BN 52021, an antagonist of the paf putative receptor; 2) the factor was inactivated by phospholipase A2 but was insensitive to lipase from Rhizopus arrhizus; 3) it exhibited the same retention time as synthetic paf during standard and reverse-phase (RP) high-pressure liquid chromatography (HPLC) elution. The paf precursors, i.e., lyso-paf and 1-O-alkyl-2-acyl-sn-glycero-3 phosphocholine, were also detected in epidermal cells, stimulated with A23187 or not. As determined by RP-HPLC analysis and confirmed by gas chromatography analysis, these precursors and the paf produced by epidermal cells exhibited more than 90% of a hexadecyl chain at the sn-1 position of the molecule. The present results demonstrate the synthesis and release of paf by normal human epidermal cells. Paf production within the epidermis might account for the development of cutaneous inflammation and the pathogenesis of many skin disorders. PMID- 2230222 TI - Immunosuppressive effects of clonidine on the induction of contact sensitization in the balb/c mouse. AB - The clonidine transdermal therapeutic system (clonidine-TTS) has been associated with a significant incidence of allergic contact sensitization. This incidence was not predicted by premarket skin sensitization testing in animals or humans. One possible explanation lies in recent findings in guinea pigs that clonidine exposure could inhibit the elicitation of skin reactions to unrelated strong contact sensitizers. However, these studies also showed that clonidine pretreatment did not appear to affect the induction of contact sensitization. On this basis, we sought to specifically evaluate the induction phase of sensitization to clonidine as an alternative means of assessing its sensitization properties. The method selected was the assay of in situ lymphocyte proliferation in lymph nodes draining the sites of clonidine exposure, a method recently promoted as an alternative means to assess contact allergenic potential. Utilizing various induction application techniques and regimens, we were consistently unable to demonstrate clonidine's allergenic potential through such an assessment of lymphocyte proliferation. We were also unable to demonstrate sensitization by in vivo ear swelling or in vitro lymphocyte blastogenesis assay techniques. However, a subsequent assessment of the effect of clonidine exposure on the induction of sensitization to unrelated strong contact allergens demonstrated a consistent 40-70% inhibition of the proliferative response to the contact allergens oxazolone and trinitrochlorobenzene. This was similar to the degree of suppression produced by the corticosteroids fluocinonide and hydrocortisone when they were tested at 80 and 10 times lower concentrations. In addition, we observed a comparable inhibition of the ear swelling response to oxazolone. These data extend our knowledge of the immunomodulatory effects of clonidine and offer additional mechanistic insights into the failure of short term predictive patch-test methods to detect this chemical's potential to induce allergic contact sensitization. PMID- 2230221 TI - Interspecies and interregional analysis of the comparative histologic thickness and laser Doppler blood flow measurements at five cutaneous sites in nine species. AB - Studies in dermatology, cutaneous pharmacology, and toxicology utilize skin from different animal species and body sites. However, regional differences exist in topical chemical percutaneous absorption studies in man and in animal. The objective of this study was to compare epidermal thickness and number of cell layers across species and body sites using both formalin-fixed paraffin and frozen sections. Cutaneous blood flow determined by laser Doppler velocimetry (LDV) was compared to histologic data. Six animals of each of the following species were used: monkeys, pigs, dogs, cats, cows, horses, rabbits, rats, and mice. Cutaneous blood flow was determined and 6-mm skin biopsies were taken directly from the following sites: buttocks, ear, humeroscapular joint, thoracolumbar junction, and abdominal area. When the two histologic methods were compared across all species and body sites, the thickness of the epidermis was significantly greater, and the thickness of the stratum corneum significantly less, in paraffin sections versus frozen sections (p less than 0.05). There were no differences in the number of viable cell layers determined by both methods. The values for LDV-determined blood flow did not significantly correlate (p greater than 0.05) to epidermal or stratum corneum thickness. However, regional and species differences were noted in all these parameters. In conclusion, these data indicate that thickness and LDV blood flow are independent and must be evaluated separately when comparisons are made between species and body sites. This work provides a data base for future comparative studies in which a knowledge of skin thickness or blood flow might be important variables. PMID- 2230223 TI - Targeting gene expression to the epidermis of transgenic mice: potential applications to genetic skin disorders. AB - The ability to specifically target gene expression to the epidermis of transgenic mice offers the exciting possibility of creating animal models of certain skin disorders that are inherited in man. It may be possible to produce mouse models of dominantly inherited keratinization disorders by targeting the expression of mutant genes encoding the major differentiation products of the epidermis, such as the differentiation specific keratins, filaggrin and cell envelope proteins. Mouse models for other skin disorders associated with abnormal regulation of growth, such as psoriasis, may be generated by targeting the overexpression of cytokines and growth factors, which are thought to play important roles in the pathogenesis of this disease. The development of currently unavailable animal models for certain inherited human skin diseases would not only contribute to our understanding of the pathogenesis of these diseases at the molecular level, but also provide interesting models for therapeutic intervention. PMID- 2230224 TI - Unusual cholesterol esters in the sebum of young children. AB - Cholesterol esters (CE) having fatty acids of more than 18 carbons are a prominent feature of fetal skin surface lipid (vernix caseosa), but are a minor component of adult lipid. The difference may be related to the fact that fetal sebaceous glands generally synthesize little lipid. If so, it would be expected that prepuberal children, who also have very inactive glands, would secrete CE with a large proportion of very-long-chain fatty acids. To test this conjecture, skin surface CE from young children were isolated and analyzed. Sebum was extracted from the hair of 38 children, aged six to nine. To obtain a measure of sebaceous lipogenesis, the class composition of the lipid was determined by quantitative thin-layer chromatography and the ratio of wax esters/[cholesterol + cholesterol esters] (WE/[CH + CE]) was calculated. CE were then isolated from the lipid and hydrolyzed. The freed fatty acids were converted to fatty acid methyl esters (FAME) and analyzed by capillary gas chromatography to determine the proportion with more than 18 carbons. FAME from five of the subjects were then separated into saturated and monounsaturated fractions and analyzed again by gas chromatography to identify chain types. Ratios of WE/[CH + CE] ranged from 0.08 to 2.8 in the subjects. The proportion of CE FAME with more than 18 carbons ranged from 15 to 72%, with the highest proportion being found in the children with the lowest WE/[CH + CE]. The saturated FAME were mostly iso- or anteiso branched, whereas the monounsaturated FAME were mostly straight-chain extension products of 16: 1 delta 9 or 18: 1 delta 9. PMID- 2230225 TI - Transforming growth factor-beta modulates plasminogen activator activity and plasminogen activator inhibitor type-1 expression in human keratinocytes in vitro. AB - Transforming growth factor beta (TGF-beta) is a multifunctional mediator with effects on cellular growth, differentiation, and extracellular matrix (ECM) metabolism. Because TGF-beta stimulates fibronectin expression in cultured human keratinocytes, we wished to determine whether it might also affect ECM degradation through the plasminogen activator (PA)-plasminogen activator inhibitor (PAI) system. Immunofluorescence of human keratinocytes using a monospecific antiserum to type 1 PAI (PAI-1) showed enhanced cellular and ECM staining when they were cultured in the presence of TGF-beta. The antiserum also identified an Mr 50,000 protein in conditioned media that was markedly enhanced by TGF-beta. A corresponding stimulation of PAI-1 mRNA was demonstrated by quantitative RNA blot analysis. Total plasminogen activating activity of conditioned medium was markedly decreased by TGF-beta. Zymography showed this to be at least partially due to decreased secreted urokinase activity. TGF-beta may play an important role in stabilizing the provisional matrix synthesized by keratinocytes in healing wounds. PMID- 2230226 TI - Inherited mouse mutations as models of human adnexal, cornification, and papulosquamous dermatoses. AB - Nearly 100 mouse mutations have been described as causing some type of abnormality of the skin or hair. As only a few of these mutations have been studied in detail, they remain an untapped resource for furthering knowledge of basic cutaneous physiology and understanding the pathophysiology of analogous diseases in humans. Several diverse murine mutations are discussed. These include "asebia," a mildly hyperkeratotoic disorder with sebaceous gland hypoplasia; "ichthyosis," an example of abnormal hair growth associated with hyperkeratosis; "rhino" and "hairless," two related examples of congenital follicular malformations; and "flaky skin", a potential animal model of eruptive psoriasis. PMID- 2230227 TI - Growth factor and proto-oncogene expression in psoriasis. AB - The expression of several proto-oncogenes and growth factors was analyzed in normal skin and psoriatic lesions by RNA blot hybridization. Isolation of intact RNA from frozen biopsy samples required immediate exposure to denaturants during tissue homogenization. Lipocortin II and cyclophilin transcripts were used as internal controls. These transcripts were abundant and slightly but significantly elevated in psoriatic lesions. When results were normalized according to these reference transcripts, there was no increase in the expression of c-myc, c-Ha ras, c-erbB (EGF receptor), c-jun, or transforming growth factor-beta (TGF-beta) transcripts in psoriatic lesions, and lesional c-fos transcripts were decreased relative to normal skin. In contrast, expression of TGF-alpha mRNA transcripts were markedly increased in psoriatic lesions even after normalization. Placement of normal or psoriatic tissue in organ culture for 2 to 4 h resulted in strong induction of c-fos, c-jun, and c-myc transcripts, but not of the other genes studied. Thus, overexpression of proto-oncogenes may be more characteristic of the epidermal response to acute injury than of the steady-state hyperplasia characteristic of psoriasis. Interferon-gamma (IFN-gamma) increased TGF-alpha mRNA levels in cultured human KC at long time intervals (24-48 h). However, of various cytokines tested, only EGF and TGF-alpha induced TGF-alpha mRNA after short time intervals (2-4 h). These results as well as the selective overabundance of TGF-alpha mRNA in psoriatic lesions among various cytokines tested suggest that activation of the EGF receptor tyrosine kinase by TGF-alpha is important in the pathogenesis of psoriatic epidermal hyperplasia. PMID- 2230228 TI - Heterosexual transmission of human immunodeficiency virus among intravenous drug users. AB - To examine sexual transmission of human immunodeficiency virus (HIV) among heterosexual intravenous drug users (IVDUs), HIV antibody status of IVDUs with intravenous drug-using sexual partners (IVSPs) was compared with that of IVDUs with no IVSPs. Initial bivariate analyses indicated IVDUs with IVSPs were more likely to be HIV antibody-positive than those with no IVSPs. Analyses by gender indicated that this relationship held for men but not women. IVDUs with IVSPs also differed from those without IVSPs demographically, in drug use, and in other sexual behaviors. When effects of other variables were controlled, no statistically significant relationship was found between injection history of sex partners and HIV status for the total sample or separately for men or women. PMID- 2230229 TI - The role of human immunodeficiency virus infection in pneumococcal bacteremia in San Francisco residents. AB - Human immunodeficiency virus (HIV) is an important risk factor for invasive pneumococcal disease, but information on clinical course and infecting serotypes is limited. To help develop strategies to reduce the morbidity due to invasive pneumococcal disease, episodes of pneumococcal bacteremia were identified by retrospective review of microbiology records (November 1983-November 1987) at 10 San Francisco hospitals and, for patients 20-55 years old living in San Francisco, HIV antibody status was determined by review of medical records. Pneumococcal isolates from one hospital were serotyped. Of 294 patients with pneumococcal bacteremia identified, 32 (11%) had AIDS at the time pneumococcal bacteremia was diagnosed and another 43 (15%) were HIV-infected but did not have AIDS; 12 HIV-infected patients developed AIDS after the episode of pneumococcal bacteremia. The rate of pneumococcal bacteremia in AIDS patients was estimated to be 9.4/1000 patient-years. Serotypes of 27 (82%) of 33 pneumococcal isolates from HIV-infected patients and 107 (90%) from 119 patients without known HIV infection were among the 23 serotypes included in the currently available polysaccharide vaccine. The rate of pneumococcal bacteremia is approximately 100-fold greater in AIDS patients in San Francisco than rates reported before the AIDS epidemic, but more than half the episodes of pneumococcal bacteremia in HIV-infected patients occurred in patients without AIDS. Data on pneumococcal serotypes causing invasive disease in HIV-infected patients suggest that the current pneumococcal vaccine, if effective in this population, could provide significant protection against pneumococcal disease. PMID- 2230230 TI - Clinical correlation and genetic polymorphism of the human immunodeficiency virus proviral DNA obtained after polymerase chain reaction amplification. AB - Polymerase chain reaction (PCR) was used to amplify a long sequence of human immunodeficiency virus (HIV) DNA, to assess the correlation between PCR signal and clinical stage of disease, and to demonstrate the genotypic variability of different HIV isolates. Twenty-four (96%) of 25 anti-HIV-reactive patients and none of 12 controls were positive for HIV proviral DNA by PCR. After quantification of the PCR signal, a significant difference in the relative amount of HIV proviral DNA per 10(5) peripheral blood mononuclear cells between symptomatic patients (Centers for Disease Control [CDC] class IV) (32,284 +/- 5225 cpm [mean +/- SE], equivalent to 802 HIV plasmid DNA copies) and patients without symptoms (CDC class II/III) (5484 +/- 1469 cpm [mean +/- SE], equivalent to 67 HIV plasmid DNA copies) was observed (P less than .01). Restriction analysis of PCR products in selected samples showed extensive genetic polymorphism between different isolates and more than one viral genotype per isolate. There was a clear correlation between the appearance of clinical symptoms in HIV infection and high levels of viral replication. PMID- 2230231 TI - Measles antibody: reevaluation of protective titers. AB - A school blood drive before a measles outbreak permitted correlation of preexposure measles antibody titers with clinical protection using the plaque reduction neutralization (PRN) test and an EIA. Of 9 donors with detectable preexposure PRN titer less than or equal to 120, 8 met the clinical criteria for measles (7 seroconfirmed) compared with none of 71 with preexposure PRN titers greater than 120 (P less than .0001). Seven of 11 donors with preexposure PRN titers of 216-874 had a greater than or equal to 4-fold rise in antibody titer (mean, 43-fold) compared with none of 7 with a preexposure PRN titer greater than or equal to 1052 (P less than .02). Of 37 noncases with preexposure PRN titer less than 1052, 26 (70%) reported one or more symptoms compared with 11 (31%) of 35 donors with preexposure PRN titers greater than or equal to 1052 (P less than .002). By EIA, no case had detectable preexposure antibody; the preexposure geometric mean titer of asymptomatic donors (220) was not significantly higher than that of symptomatic donors who did not meet the clinical criteria for measles (153) (P = .10). The study suggests that PRN titers less than or equal to 120 were not protective against measles disease and illness without rash due to measles may occur in persons with PRN titers above this level. PMID- 2230232 TI - Measles incidence, vaccine efficacy, and mortality in two urban African areas with high vaccination coverage. AB - Measles incidence, vaccine efficacy, and mortality were examined prospectively in two districts in Bissau where vaccine coverage for children aged 12-23 months was 81% (Bandim 1) and 61% (Bandim 2). There was little difference in cumulative measles incidence before 9 months of age (6.1% and 7.6%, respectively). Between 9 months and 2 years of age, however, 6.1% contracted measles in Bandim 1 and 13.7% in Bandim 2. Even adjusting for vaccination status, incidence was significantly higher in Bandim 2 (relative risk 1.6, P = .04). Even though 95% of the children had measles antibodies after vaccination, vaccine efficacy was not more than 68% (95% confidence interval [CI] 39%-84%) and was unrelated to age at vaccination. Unvaccinated children had a mortality hazard ratio of 3.0 compared with vaccinated children (P = .002), indicating a protective efficacy against death of 66% (CI 32%-83%) of measles vaccination. These data suggest that it will be necessary to vaccinate before age 9 months to control measles in hyperendemic urban African areas. PMID- 2230233 TI - Properties of strains of Escherichia coli O26:H11 in relation to their enteropathogenic or enterohemorrhagic classification. AB - Thirty-seven strains of Escherichia coli O26:H11 from infants and calves with diarrhea were examined for properties associated with enteropathogenic (EPEC) or enterohemorrhagic E. coli (EHEC). Strains were heterogeneous with respect to Vero cytotoxin (VT) production and hybridization with the EHEC plasmid-specific (CVD419) probe; 26 strains produced VT1; 1 produced VT2. Twenty-four of 27 VT+ strains and 5 of 10 VT- strains hybridized with the CVD419 probe and produced enterohemolysin; these properties are characteristic of EHEC. The strains did not hybridize with the EPEC adherence factor probe, a property characteristic of some EPEC. Nevertheless, 36 strains adhered to HEp-2 cells in a localized manner and were positive by the fluorescence actin staining (FAS) test that is considered to correlate with the ability to cause attaching and effacing lesions in vivo. EPEC and EHEC cause these lesions. Although the FAS test appeared to be the most general pathogenicity test for the O26:H11 strains, it could not be used to assign strains specifically to EPEC or EHEC groups. PMID- 2230234 TI - Fucosylated oligosaccharides of human milk protect suckling mice from heat stabile enterotoxin of Escherichia coli. AB - Human milk protects suckling mice from the diarrheagenic effects of heat-stabile enterotoxin of Escherichia coli (ST). To identify the human milk fraction responsible for this protection, pooled skimmed, deproteinated milk was passed through charcoal, whereupon lactose was separated from the oligosaccharides. The oligosaccharides contained ST-protective activity; the lactose did not. The neutral, but not the acidic, fraction exhibited protective activity against ST (22% vs. 57% mortality, respectively; P less than .001). The fucosylated, but not the nonfucosylated, subfractions of the neutral fraction contained the factor protective against ST (35% vs. 50% mortality, respectively; P less than .05). An oligosaccharide isolation scheme based on different principles produced confirmatory results. The commercially available neutral fucosylated oligosaccharides of human milk did not significantly protect the mice from the effects of ST. Thus, the protective factor against ST seems to be a minor neutral fucosyloligosaccharide of human milk. PMID- 2230235 TI - Platelet-activating factor or a platelet-activating factor antagonist decreases tumor necrosis factor-alpha in the plasma of mice treated with endotoxin. AB - When L-platelet-activating factor (PAF) or alprazolam (a PAF antagonist) was administered to lipopolysaccharide (LPS)-treated mice, the level of plasma tumor necrosis factor (TNF alpha) determined by either ELISA or a cytotoxic assay using WEHI cells was significantly lowered. The inactive stereoisomer, D-PAF, was not effective in lowering plasma TNF alpha levels in LPS-treated mice. The decrease in plasma TNF alpha induced by L-PAF or alprazolam was partly reversed by indomethacin. Despite a decrease in plasma TNF alpha, L-PAF or alprazolam caused an increase in the amount of TNF alpha mRNA present in the kidneys and the livers of LPS-treated mice, suggesting that a posttranscriptional event leading to the synthesis or release of TNF alpha was inhibited by these agents. PMID- 2230236 TI - Salmonella interactions with polarized human intestinal Caco-2 epithelial cells. AB - Polarized monolayers of the human intestinal epithelial Caco-2 cell line were grown on permeable filters and infected apically with either Salmonella choleraesuis or Salmonella typhimurium. Both Salmonella species penetrated through the monolayer, requiring 2 h before appearing in the basolateral medium. Both species caused a loss in transepithelial resistance by 3-4 h, and the monolayer's integrity was completely disrupted by 6 h. Scanning and transmission electron microscopy revealed that the bacteria interacted with well-defined apical microvilli and caused disruptions in the brush border, including elongation and denuding of the microvilli. The cytoplasm was also disrupted locally, with blebs protruding from the apical surface. The bacteria entered (invaded) these cells and were enclosed in membrane-bound vacuoles within the cytoplasm. By 6 h there were many bacteria within most Caco-2 cells, and these organisms caused serious cytopathic consequences. These morphologic observations correlated well with animal infection models, indicating that this in vitro system will be useful to study pathogens that interact with human intestinal epithelia. PMID- 2230237 TI - Antimicrobial resistance of Shigella isolates in the USA: the importance of international travelers. AB - A nationwide sample of Shigella isolates was collected and tested for resistance to 12 antimicrobial agents to assess the prevalence and epidemiologic correlates of antimicrobial resistance in Shigella. Of the isolates, 32% were resistant to ampicillin, 7% to trimethoprim-sulfamethoxazole, and 0.4% to nalidixic acid. Fifty (20%) of 252 isolates were associated with foreign travel. The best predictor of clinically important resistance was a history of foreign travel: 20% of isolates from foreign travelers showed trimethoprim-sulfamethoxazole resistance, compared with only 4% of isolates from those without such a history. Quinolone resistance was not identified in travel-related isolates, and quinolones may be more appropriate for initial therapy of travel-related shigellosis than is trimethoprim-sulfamethoxazole. PMID- 2230238 TI - Cefuroxime treatment failure of nontypable Haemophilus influenzae meningitis associated with alteration of penicillin-binding proteins. AB - A 10-year-old boy presented with nuchal rigidity and cerebrospinal fluid (CSF) leukocytosis initially and again on day 6 of intravenous cefuroxime therapy (200 mg/kg/day). Both CSF specimens yielded nontypable beta-lactamase-negative Haemophilus influenzae that were susceptible by disk tests but relatively resistant to cefuroxime (MIC, 8- to 16-fold greater than that of control isolates). To define the mechanism of resistance, the cefuroxime resistance marker was transformed to a susceptible H. influenzae recipient; inactivation and permeability of beta-lactam substrate were tested and the penicillin-binding protein (PBP) profiles were examined. Inactivation of beta-lactam substrate was not detected and reduced permeability was not found. However, reduced beta-lactam binding to PBPs 4 and 5 was observed; 18- to 27-fold more penicillin and 2.5-to 4 fold more cefuroxime was required to saturate or block 50% of the binding sites of these PBPs, respectively. Thus, reduced affinity of PBPs 4 and 5 for beta lactam substrate appears to be the mechanism of cefuroxime resistance in this strain. The reduced affinity of these targets appears to have contributed to the bacteriologic and clinical failure in this patient. PMID- 2230239 TI - Prevention of catheter-associated urinary tract infection with a silver oxide coated urinary catheter: clinical and microbiologic correlates. AB - In a prospective clinical trial involving 482 acutely hospitalized patients, the overall incidence of catheter-associated urinary tract infection (UTI; 10%) was similar in recipients of a silver oxide-coated urinary catheter (silver catheter) or a control silicone catheter. However, female sex and absence of antimicrobial use were independently associated with an increased risk of UTI. After stratification for these variables, the silver catheter reduced the incidence of UTI among women not receiving antimicrobial agents (19% for control catheter vs. 0 for silver catheter, P = .04; confidence interval for the difference in incidence, 0.4%-38%) but not in the other subgroups. Gram-positive UTI was associated with absence of antimicrobial use, the control catheter, and catheter care violations. Gram-negative and candidal UTIs were more common after 7 days of catheterization, and candidal UTI was associated with being female and antimicrobial use. These findings demonstrate that several clinical variables influenced the incidence and microbiology of catheter-associated UTI and that the silver catheter appeared to prevent UTI among women not receiving antimicrobials. PMID- 2230240 TI - Circulating immune complex-associated parasite antigens in human onchocerciasis. AB - This study identified and characterized parasite antigens in sera from humans infected with Onchocerca volvulus. Immune complexes were precipitated from human sera with polyethylene glycol and analyzed by immunoblot with rabbit antibodies to O. volvulus. A 23-kDa parasite antigen was detected in sera from 17 of 23 Nigerian onchocerciasis patients and 5 of 10 endemic controls. Other parasite antigens with apparent molecular masses of 62, 66, and 70 kDa were less consistently observed. These antigens were not present in Nigerian or US nonendemic control sera, in sera from patients with various other parasitic infections, or in sera from US patients with autoimmune diseases. Biochemical studies indicated that these antigens are nonglycosylated acidic proteins that do not contain phosphorylcholine. These antigens may be useful as targets for improved diagnostic tests for onchocerciasis based on parasite antigen detection. PMID- 2230241 TI - Coccidioidomycosis in human immunodeficiency virus-infected patients. AB - Coccidioidomycosis is at best a complicated fungal infection; often it is life threatening. Coccidioidomycosis is confined epidemiologically to the southwestern region of the USA, and most cases have occurred in that area, particularly in Arizona. However, we have seen several cases in San Francisco in patients with only a history of travel to endemic areas. In part because of its regional distribution, information about the clinical presentation, diagnosis, and treatment of patients with coccidioidomycosis has lagged behind information about other, more commonly encountered AIDS-associated opportunistic infections. Drs. Galgiani and Ampel have probably had the largest single experience with coccidioidomycosis in individuals infected with the human immunodeficiency virus. These specialists share their experience and make recommendations as to how these complicated conditions should be approached. PMID- 2230242 TI - Antibody affinity in infants after immunization with conjugated capsular polysaccharide from Haemophilus influenzae type b. AB - The affinities of IgG antibodies to Haemophilus influenzae b capsular polysaccharide (polyribosyl ribitol phosphate [PRP]) elicited 1 month after immunization of 47 infants 2-greater than 18 months of age with a PRP-outer membrane protein conjugate (PRP-OMP) were measured by ELISA. Thirty-four sera had affinities distributed normally about a logarithmic mean of 3.2 x 10(5) l/mol, but 13 samples had undetectable affinities (less than 10(4) l/mol). Median affinities of sera from children 2-6 (1.5 x 10(5) l/mol) and 7-11 months of age (1.6 x 10(5) l/mol) were significantly greater than the median affinities of sera from infants 12-18 (1.8 x 10(4) l/mol) or greater than 18 months of age (4.2 x 10(4) l/mol). Sera from children greater than 18 months of age vaccinated with PRP conjugated to diphtheria toxoid had a median affinity of 6.1 x 10(4) l/mol, equivalent to that of the same age group vaccinated with PRP-OMP. Children vaccinated with PRP conjugate vaccines may produce antibodies of very low affinity, a finding that may have significance for protection from invasive disease. PMID- 2230244 TI - Differentiation of Shiga toxin and Vero cytotoxin type 1 genes by polymerase chain reaction. AB - Two sets of synthetic oligonucleotide primers were used in a polymerase chain reaction technique to distinguish genes for Shiga toxin in Shigella dysenteriae 1 and type 1 Vero cytotoxin (VT1) in Escherichia coli. VT1a and VT1b primers directed at a common 130-base-pair (bp) fragment of the stx and sltI genes detected template nucleic acid in both Shiga toxin-positive S. dysenteriae 1 and VT1-producing E. coli strains. VT1c and VT1d primers, targeting a 140-bp fragment of the promoter region of the sltIA gene, were negative in the polymerase chain reaction with S. dysenteriae 1 nucleic acid and positive with nucleic acids from all strains found to produce VT1 in toxin-specific neutralization tests. Primer specificity was determined in the polymerase chain reaction using nucleic acid extracted from 49 strains of representative enteric pathogens defined in terms of their toxigenicity. PMID- 2230243 TI - Pneumococcal anticapsular antibodies in patients with chronic cardiovascular and obstructive lung disease in The Netherlands. AB - Differences in pneumococcal anticapsular antibody concentrations were assessed among patients with various chronic disorders and among young (25-35 years of age) and older adults (55-65 years). Antibody concentrations were determined by ELISA, using the whole 23-valent pneumococcal polysaccharide vaccine as antigen. No differences in mean or distribution of serum antibody concentrations were found among young adults (either healthy or asthmatic) or among older adults (healthy or with chronic obstructive pulmonary or chronic cardiovascular disease). Each group included individuals with low antibody levels. Therefore, the enhanced susceptibility to pneumococcal infections reported for some groups at risk, that is, elderly individuals and patients with chronic obstructive pulmonary or chronic cardiovascular disease, cannot be attributed solely to low anticapsular antibody concentrations. PMID- 2230245 TI - Neisseria mucosa endocarditis. AB - A case of Neisseria mucosa tricuspid valve endocarditis in an intravenous drug abuser is described. The patient was treated initially with intravenous penicillin G followed by oral penicillin VK but relapsed. He was cured after 4 weeks of combined therapy with penicillin G and gentamicin. In vitro synergy studies performed on the patient's and two other isolates revealed synergy in all three. Thus, combination therapy is recommended for treatment of recalcitrant cases of bacterial endocarditis caused by N. mucosa. PMID- 2230246 TI - Detection of interleukin-3 in the serum of mice infected with Mycobacterium lepraemurium. AB - Infection of mice by Mycobacterium lepraemurium is accompanied by ablation of erythropoiesis in the bone marrow and gross enlargement of the spleen. This, together with increased monocytopoiesis and the earlier demonstration of macrophage colony-stimulating factor in the serum of infected mice, suggested the activity of additional cytokines. Eight weeks after infection of mice by M. lepraemurium, interleukin-3 (IL-3) activity was demonstrated in the serum (titer, 1:3200). The serum titer of IL-3 activity was maximal after 13 weeks (greater than 1:6400) and was slightly reduced after 18 weeks (1:6400). That the IL-3 activity detected in the serum of the M. lepraemurium-infected mice reflected the presence of IL-3 itself was confirmed by a neutralization assay using anti-murine IL-3 antibodies; IL-3 activity in the serum of mice 13 weeks after infection was completely abolished by the anti-IL-3 antibodies. Finally, a 1-kb signal of IL-3 RNA was detected in the spleens of M. lepraemurium-infected mice 13 weeks after infection. PMID- 2230247 TI - Motility of Lyme disease spirochetes in fluids as viscous as the extracellular matrix. AB - When properties of extracellular fluids that might regulate the ability of the Lyme disease spirochete to locomote were investigated, the rate of progression correlated with viscoelasticity. Such spirochetes flexed and rotated but did not progress in relatively nonviscous fluids and migrated increasingly rapidly as the viscous characteristics of the medium increased. The viscoelastic properties of various kinds of hyaluronic acid resembled those of a methylcellulose standard. The maximum velocity that spirochetes achieved in such solutions related directly to viscoelasticity rather than to chemical composition. Spirochetes remained motile during 3 h of observation despite 100-fold dilution of the standard nutrient medium. The immobility of Lyme disease spirochetes in media less viscous in character than fixed tissue suggests dissemination via the intercellular ground substance of skin. PMID- 2230248 TI - Treatment of symptomatic children infected with human immunodeficiency virus. PMID- 2230249 TI - Antibody-mediated enhancement of respiratory syncytial virus infection. PMID- 2230251 TI - Disseminated bacille Calmette-Guerin infection in an AIDS patient 30 years after BCG vaccination. PMID- 2230250 TI - Pseudofailure of zidovudine prophylaxis after a human immunodeficiency virus positive needlestick. PMID- 2230253 TI - Cefepime for treatment of experimental chronic osteomyelitis due to Staphylococcus aureus. PMID- 2230252 TI - Recovery of viable bacteria from pelvic lymph nodes of patients with gynecologic tumors. PMID- 2230254 TI - Persistent chronic active cervicitis: a newly noted finding in an animal model of chlamydial genital disease. PMID- 2230255 TI - Prevalence of homozygous C4B deficiency in patients with deficiencies of terminal complement components and meningococcemia. PMID- 2230256 TI - AZT demonstrates anti-HIV-1 activity in persistently infected cell lines: implications for combination chemotherapy and immunotherapy. AB - A sensitive and quantitative focal immunoassay has been used to measure the effects of three different therapeutic agents on tissue culture cells infected with human immunodeficiency virus (HIV). The effects of the drugs were studied on both acutely and persistently infected CD4+ cell lines. The three agents, azidothymidine (AZT), interferon-alpha (IFN-alpha), and an anti-HIV envelope antibody coupled to ricin A chain, were tested alone and in combination. AZT was found to have its greatest effect during early stages of the infection, but also had an action on persistently infected T cell lines. The effect of AZT on persistently infected cells was seen within 24 h, increased with extended exposure to the drug, and persisted after its removal. IFN-alpha had variable effects on acutely infected cells but suppressed chronic infection. Combinations of the therapeutic agents were studied. Using a model that allowed for treatment during both acute and persistent stages of infection, the most effective combination in suppressing HIV infection was the continual use of both AZT and IFN-alpha at the highest tolerable doses. Knowledge of the efficacy of AZT on persistently infected cells will allow for the most effective design of clinical protocols. PMID- 2230257 TI - Quantitative detection of brain aberrations in human immunodeficiency virus type 1-infected individuals by magnetic resonance imaging. AB - The brains of 65 individuals with antibodies to human immunodeficiency virus type 1 (HIV-1), 20 HIV-1 seronegative homosexual men, and 75 heterosexual controls were examined by a quantitative magnetic resonance imaging technique. A white matter aberration was detected most frequently in patients with AIDS-related complex (ARC) or AIDS, but also in asymptomatic HIV-1 seropositive persons and in HIV-1 seronegative homosexual men, of whom two of three tested were reactive for HIV-1 DNA by polymerase chain reaction. The aberration was not found in the control group. Brain atrophy was mainly confined to patients with ARC or AIDS. The brain lesions correlated with the presence of HIV-1 in cerebrospinal fluid and with elevated levels of beta 2-microglobulin and neopterin. The most pronounced brain aberrations were in patients with AIDS-dementia complex. These findings indicate that brain aberrations may occur in persons in the early stages of HIV-1 infection, although to no greater extent than in HIV-1 seronegative homosexual men. The occurrence of pronounced brain lesions seems to be associated with the presence of an advanced immunodeficiency. PMID- 2230258 TI - Occurrence of groups A and B of respiratory syncytial virus over 15 years: associated epidemiologic and clinical characteristics in hospitalized and ambulatory children. AB - Over 15 years respiratory syncytial virus (RSV) isolates from 1209 hospitalized and ambulatory children were examined for strain group and in a subset for subgroup to determine the associated epidemiologic and clinical characteristics. Three patterns of yearly outbreaks existed: (1) strong predominance of group A strains (9 years with 83%-100% A strains), (2) relatively equal proportions of group A and B strains (4 years), and (3) strong predominance of group B strains (78%-85%) in 2 years, separated by a decade. The first pattern of highly dominant A strains occurred in cycles of 1 or 2 consecutive years with a single intervening year in which B strains were greater than or equal to 40% of the isolates. Subgroups A1 and A2 predominated, while B2, 3, and 4 occurred almost equally. A greater clinical severity for Group A strains was suggested by children with group A infections requiring intensive care significantly more often (15.4 vs. 8.3%, P = .008). Further, strongly dominant A strain years were associated with higher proportions of RSV admissions requiring intensive care (16.6% vs. 5.5%, P less than .01). Strains of subgroups A2 and B4 were more frequently found in hospitalized patients and A1 in outpatients, and the 2 years with the highest rates of intensive care admissions were those in which subgroup A2 dominated. PMID- 2230259 TI - Pichinde virus infection in strain 13 guniea pigs reduces intestinal protein reflection coefficient with compensation. AB - Pichinde virus inoculation into strain 13 guinea pigs is a model with features reputed to be similar to hemorrhagic fever in humans. Although the infection is lethal by day 13-19, guinea pigs of approximately 600 g do not show edema or effusions. This raises the questions of whether capillary damage is present in such infected animals and, if it is, why edema is absent. The effects of Pichinide virus on protein transport across jejunal capillaries were examined in 38 normal and 7 infected strain 13 guinea pigs 12 days after inoculation. The latter lost 20.3% body weight but maintained normal blood pressure, serum protein concentration, and jejunal lymph flow. However, their protein solvent drag reflection coefficient (sigma) was reduced to .52 +/- .03 (mean +/- SE) from .73 +/- .02 (2P less than .001), while permeability-surface area product was not changed. In the absence of gross edema or effusions, Pichinde virus-infected guinea pigs demonstrated a leaky gut capillary wall to protein compatible with an increase in pore size or large pore number less than sufficient to change permeability-surface area product. Compensatory mechanisms that prevent edema at this stage are efficient and may include reduced capillary pressure or some degree of capillary flow stasis. PMID- 2230260 TI - Partial characterization of Chlamydia trachomatis isolates resistant to multiple antibiotics. AB - In vitro susceptibility testing was done on urogenital isolates of Chlamydia trachomatis from five patients, four of whom were suspected treatment failures. At least one isolate from each patient was resistant to tetracycline at concentrations greater than or equal to micrograms/ml, although less than 1% of a population of organisms showed high-level resistance. Fully resistant populations selected by passage through 8 micrograms/ml tetracycline either died or lost their resistance on further passage in antibiotic-free medium. Relatively large inocula were required to demonstrate resistance, and morphology of inclusions was altered at high tetracycline concentrations. The observed resistance may be a new characteristic of the organism or merely newly recognized. Isolates resistant to tetracycline were resistant to doxycycline, erythromycin, sulfamethoxazole, and clindamycin but sensitive to rifampin, ciprofloxacin, and ofloxacin. Thus, resistance to tetracycline, erythromycin, and clindamycin occurs in C. trachomatis and may be a factor in some treatment failures. PMID- 2230261 TI - Bacterial meningitis in the United States, 1986: report of a multistate surveillance study. The Bacterial Meningitis Study Group. AB - A prospective, laboratory-based surveillance project obtained accurate data on meningitis in a population of 34 million people during 1986. Haemophilus influenzae was the most common cause of bacterial meningitis (45%), followed by Streptococcus pneumoniae (18%), and Neisseria meningitidis (14%). Rates of H. influenzae meningitis varied significantly by region, from 1.9/100,000 in New Jersey to 4.0/100,000 in Washington state. The overall case fatality rates for meningitis were lower than those reported in several studies from the early 1970s, suggesting that improvements in early detection and antibiotic treatment may have occurred since that time. Concurrent surveillance was also performed for all invasive disease due to the five most common causes of bacterial meningitis. Serotypes of group B streptococcus other than type III caused more than half of neonatal group B streptococcal disease and mortality, suggesting that an optimal vaccine preparation must be multivalent. Of the organisms evaluated, group B streptococcus was the second most common cause of invasive disease in persons greater than 5 years old. PMID- 2230262 TI - A large outbreak of antibiotic-resistant shigellosis at a mass gathering. AB - In July 1987, a large outbreak of shigellosis occurred among attendees at a mass gathering in a national forest, the annual Rainbow Family Gathering. Sanitation in the campsite was poor, allowing widespread transmission of disease, probably by food, water, and person-to-person spread. The attack rate may have been greater than 50% among the estimated 12,700 attendees. The outbreak was caused by Shigella sonnei, resistant to ampicillin, tetracycline, and trimethoprim sulfamethoxazole; the organism was of colicin type 9 and contained a 90-kilobase plasmid not found in non-outbreak-related strains. The dispersal of the group resulted in nationwide dissemination of the organism, and outbreaks in three states were linked to transmission from attendees at the Gathering. This outbreak demonstrates the potential for rapid dissemination of disease in such a setting and the necessity for careful planning of mass gatherings. PMID- 2230263 TI - Prevalence and diagnosis of Legionella pneumonia: a 3-year prospective study with emphasis on application of urinary antigen detection. AB - During a 3-year period the frequency of legionellosis in hospitalized patients with community-acquired and nosocomial pneumonias was 3.4% (23/684 cases) and 5.9% (33/559), respectively. Of the diagnostic tests evaluated, detection of Legionella pneumophila serogroup 1 antigen in urine had the highest sensitivity, with 86% of culture-proven cases being positive. Sensitivities of serologic tests and examination of respiratory secretions (culture and direct immunofluorescence) were 36% and 26%, respectively. The diagnostic value of serology and of examination of respiratory secretions can be low when specimens are obtained and processed under the typical conditions of hospitalization. Urinary antigen detection represents an important diagnostic addition, and examination of postmortem lung tissue from fatal cases with pneumonia is an important adjunct for estimating the prevalence of legionellosis and for assessing the effectiveness of premortem diagnostic tests. PMID- 2230264 TI - Tumor necrosis factor-alpha plays a role in host defense against Histoplasma capsulatum. AB - Tumor necrosis factor-alpha was detected in supernatants collected from BALB/c mouse peritoneal macrophages incubated continuously with Histoplasma capsulatum. The levels of TNF alpha measured by actinomycin D bioassay peaked within hours after exposure and then greatly declined by 24 h. TNF alpha was also measured in bronchoalveolar lavage fluid from BALB/c mice challenged intranasally with H. capsulatum. Lavage fluid TNF alpha levels exhibited the same pattern as the in vitro supernatants; they peaked within hours after challenge and lower levels were detected at 24 h. Treatment of mice with anti-TNF alpha antibody accelerated mortality in response to systemic infection and significantly increased tissue colony counts in the liver and spleen. In the murine model, TNF alpha is produced in response to H. capsulatum and appears to play some role in host defense to infection. PMID- 2230266 TI - Diagnosis of intestinal amebiasis using salivary IgA antibody detection. AB - This investigation sought to determine whether detection of salivary IgA antibodies to Entamoeba histolytica could identify intestinal amebic infections among 223 school children. Four groups of children were identified through coproparasitoscopic examination: E. histolytica as other parasites only (20%); and parasite-free (25%). The diagnostic accuracy of salivary IgA antibodies to an E. histolytica membrane extract was 91.5% (sensitivity, 85%; specificity, 98%), maintaining high predictive value at different prevalences. Also, a positive correlation (r = .753, P less than .001) was observed between fecal E. histolytica membrane antigen levels and salivary IgA antibody activity. Measurement of IgA antibodies in saliva may be useful in diagnosing intestinal infections with E. histolytica within a wide range of prevalences. Moreover, sampling of saliva may be a useful non invasive test for immunoepidemiologic surveys. PMID- 2230265 TI - Bacterial infections in patients with visceral leishmaniasis. AB - Bacterial infections are often seen in patients with visceral leishmaniasis. To determine the incidence of such infection and the more common infectious agents, 30 consecutive patients with visceral leishmaniasis were followed throughout hospitalization. There were 24 episodes of bacterial infection in 18 patients (60%). The incidence of bacterial infections in these patients was 22.2/1000 days of admission. The proportion of patients becoming infected by time was significantly greater in the visceral leishmaniasis group than in controls (P less than .01). The skin, respiratory tract, and middle ear were the most common sites of infection, and Pseudomonas aeruginosa and Staphylococcus aureus were the most common agents. Low-grade-virulence bacteria (e.g., Serratia and Providencia species) were also isolated from some cases. Bacterial infections (mainly nosocomial) in patients with visceral leishmaniasis tend to be severe and can cause death. When bacterial infection is suspected in these patients, empiric antibiotic therapy should be started immediately, including coverage for P. aeruginosa and S. aureus, after appropriate diagnostic procedures are taken. PMID- 2230267 TI - The use of corticosteroids in Pneumocystis carinii pneumonia. PMID- 2230268 TI - Seroprevalence of human T cell leukemia viruses in selected populations of homosexual men. AB - This study sought to define the seroprevalence of human T cell leukemia virus (HTLV) types I and II in selected populations of homosexual men. Serum specimens were screened for antibodies to HTLV and to human immunodeficiency virus (HIV) by enzyme immunoassay; successive testing of specimens with positive results was done by Western blotting and radioimmunoprecipitation assay (RIPA) and then by polymerase chain reaction (PCR) assay on available peripheral blood mononuclear cells (PBMC). Of 1290 specimens, only 4 had antibodies against HTLV confirmed by RIPA. PCR analysis of DNA from PBMC from two subjects showed one to be HTLV-I and the other to be HTLV-II; both men also had HIV antibodies. These results demonstrate a lower seroprevalence rate for HTLV than some previous studies and emphasize the need for specific confirmatory tests. PMID- 2230269 TI - Confocal microscopic detection of human immunodeficiency virus RNA-producing cells. AB - A central anomaly in the pathogenesis of AIDS is that few actively infected CD4+ cells (1 in 10(4)-10(5) have been detected in the peripheral blood, even though dramatic depletion (often greater than 90%) of CD4+ cells is the hallmark of disease progression. A sensitive, 35S-based human immunodeficiency virus (HIV) RNA in situ hybridization technique was coupled with a new detection method, confocal laser scanning microscopy, to examine transcriptionally active HIV infected cells from individuals at different disease stages. In 35 symptomatic HIV-infected individuals (AIDS and AIDS related complex), an average of 1 in 350 mononuclear cells produced HIV RNA. In contrast, in an asymptomatic group of 30 individuals, an average of 1 in 2000 mononuclear cells produced HIV RNA. These data, obtained using this improved detection method, suggest there are more HIV RNA-producing cells in HIV-infected individuals than previously reported. In addition, increased numbers of HIV transcribing cells were found to correlate with declining clinical condition as assessed by Karnofsky performance score. These data suggest that viremia per se may account for the pathologic consequences in HIV infection. PMID- 2230270 TI - Frequency of indeterminate western blot tests in healthy adults at low risk for human immunodeficiency virus infection. The NIAID AIDS Vaccine Clinical Trails Network. AB - As part of a phase 1 trial of a candidate AIDS vaccine, blood specimens were collected from 168 healthy adult volunteers at minimal or no risk for becoming infected with human immunodeficiency virus type 1 (HIV-1). These specimens were screened for evidence of HIV-1 infection by enzyme immunoassay (EIA) and the Biotech/Du Pont Western blot (n = 168), culture (n = 122), and polymerase chain reaction assay (n = 20). None of the subjects had a positive test result by any of these assays, but 32% had indeterminate Western blot tests, most of which demonstrated a single band of low intensity. The most common bands were p24 (47%), p55 (34%), and p66 (36%); envelope bands were unusual (gp41, 2%; gp120, 2%). No serum specimen collected after 2-11 months from individuals with indeterminate Western blot results was positive by EIA or Western blot. There was 91% agreement in the test results of the first and second serum samples when the same lot of Western blot kit was used but only 36% agreement when different lots were used. The Biotech/Du Pont Western blot kit thus frequently yields indeterminate test results in the absence of HIV-1 infection, the reproducibility of which is subject to lot-to-lot variability. PMID- 2230271 TI - Transmission of Chlamydia pneumoniae in young children in a Japanese family. AB - Chlamydia pneumoniae strain TWAR was isolated from the respiratory tract of a 5 year-old girl suffering from pneumonia. The IgM and IgG antibody titers to TWAR were 1:32 and 1:128, respectively. Cultures and serology for other common bacterial and viral respiratory pathogens were negative. Although she was treated with 35 mg/kg/day rokitamycin, TWAR was repeatedly isolated after treatment. Her 3-year-old sister developed acute bronchitis, and TWAR was isolated from her nasopharynx. She was treated with 43 mg/kg/day erythromycin with prompt improvement, and TWAR was not isolated after treatment. Although her mother, grandmother, and 8-month-old sister suffered from respiratory illness during these periods, TWAR was not isolated from them. The repeated isolations from the index patient suggest that infection was transmitted from sister to sister. This case represents the first reported isolation of TWAR from young children in the same household and the first from Japan. PMID- 2230272 TI - Pilot trial of selective decontamination for prevention of bacterial infection in an intensive care unit. AB - Selective decontamination of the oropharynx and gastrointestinal tract with nonabsorbable antimicrobials and sucralfate, a stress ulcer prophylactic that maintains the normal gastric acid bacterial barrier, were compared for prevention of pneumonia in a cardiac surgery intensive care unit. Over 8 months, 51 patients received selective decontamination and 56 received sucralfate. The selective decontamination regimen included polymyxin, gentamicin, and nystatin given as an oral paste and as a solution; patients also received standard antacid or histamine2 blocker stress ulcer prophylaxis. Patients in the selective decontamination group had significantly less colonization of the oropharynx and stomach by gram-negative bacilli (12% vs. 55%, P less than .001), significantly fewer infections due to gram-negative bacilli (6% vs. 20%, P = .02), and fewer infections overall (12% vs. 27%, P = .04). There was one episode of pneumonia in the selective decontamination group and five in the sucralfate group. Mortality and length of stay did not differ between the groups, but those receiving selective decontamination had less than one-third as many days of systemic antibiotic therapy with no increase in colonization or infection with resistant gram-negative bacilli. Thus, selective decontamination appeared to reduce both extrapulmonary and pulmonary infections. PMID- 2230273 TI - Occurrence of secondary attenuating mutations in avirulent Salmonella typhimurium vaccine strains. AB - The attenuating delta aroA554 mutation in Salmonella typhimurium strain SL3261 was complemented in vitro by selecting for AroA+ recombinant DNA clones. SL3261 containing cloned aroA+ genes did not require exogenous phenylalanine, tryptophan, tryosine, p-aminobenzoic acid, or dihydroxybenzoic acid for growth in defined media. Cloned aroA+ genes did not restore wild-type virulence to SL3261, however, in a murine typhoid model. The delta aroA554 mutation was transduced into S. typhimurium strain SR-11, a mouse-virulent strain recently passaged in mice. The SR-11 delta aroA554 mutant was highly attenuated for mice challenged parenterally. The same cloned aroA+ genes isolated in SL3261 restored the virulence of the SR-11 delta aroA554 mutant to that of wild-type SR-11. These results suggest that while the delta aroA554 allele remains effective in reducing S. typhimurium virulence, laboratory passage of attenuated vaccine strains may lead to the accumulation of additional attenuating defects. PMID- 2230274 TI - Nasal carriage of Staphylococcus aureus: correlation with hormonal status in women. AB - In view of recent observations on hormone-microorganism interactions, a study of Staphylococcus aureus nasal carriage in relation to sex-hormone status was undertaken. Prospectively in 479 women attending a colpocytologic clinic, hormonal status was assessed by determining the karyopyknotic index (KI) on smears stained by the Papanicolaou method. Rates of S. aureus nasal carriage were 29.3% in premenopausal women and 21.9% in postmenopausal women (P not significant). Carriage rates were significantly higher (P = .026, chi 2 7.32) for women with high KIs (40.7%) than for those with intermediate and low KIs (27.03% and 25.1%, respectively). S. aureus nasal carriage also correlated independently and significantly with previous antibiotic use and the presence of insulin treated diabetes mellitus. This preliminary observation confirms an association between levels of sex hormones as reflected by the KI and S. aureus nasal carriage rates. PMID- 2230275 TI - Effects of albendazole on Echinococcus multilocularis infection in the Mongolian jird. AB - Albendazole chemotherapy of larval Echinococcus multilocularis was studied in the Mongolian jird by administration of medicated feed at various concentrations and durations. The effects were evaluated by comparison of treated and control groups in terms of host mortality, larval metastases to the lungs, and final weight and histologic appearance of larval tissue. Viability of larval tissue at necropsy of each animal was tested by inoculation into two noninfected jirds. Albendazole medicated feed (0.05%-0.10%) significantly inhibited larval growth. Other effects of the drug included larval degeneration and necrosis, inhibition of protoscolex formation, decreased pulmonary metastases, and reduced mortality of hosts. Adverse effects on the parasite correlated significantly with serum albendazole metabolite levels and duration of therapy. However, serum albendazole levels in jirds equal to or exceeding concentrations achieved in humans receiving daily doses of 10 mg/kg of body weight did not kill the parasite. PMID- 2230276 TI - Activity of the anthelmintic benzimidazoles against Giardia lamblia in vitro. AB - In vitro growth of the protozoan parasite Giardia lamblia was highly sensitive to certain anthelmintic benzimidazoles. Albendazole and mebendazole were 30- to 50 fold more active than metronidazole and 4- to 40-fold more active than quinacrine. Thiabendazole, a noncarbamate benzimidazole, was less active. Since lack of intestinal absorption makes mebendazole an attractive new antigiardial agent, its in vitro activity was further characterized. At low concentrations (0.05 micrograms/ml) mebendazole had a static effect on G. lamblia growth; however, lethal activity was observed at a concentration fivefold lower (0.3 micrograms/ml) than necessary for the cidal agent metronidazole. Two observations are consistent with a microtubule target for mebendazole. First, attachment of cells to the culture tube, mediated by the ventral disk and flagella, was rapidly disrupted by mebendazole treatment. Second, the characteristic cell structure was grossly distorted by treatment. No mebendazole-resistant G. lamblia were detected in a population of 10(8) cells. PMID- 2230277 TI - Correct structure of repeating unit of group B Streptococcus type III capsular polysaccharide. PMID- 2230278 TI - Serum neopterin and interleukin-6 levels in chronic fatigue syndrome. PMID- 2230279 TI - Helicobacter pylori: has it a part in the lesion of the gastroesophageal reflux? PMID- 2230280 TI - Crepitant myonecrosis caused by Klebsiella pneumoniae in an immunocompromised diabetic patient. PMID- 2230281 TI - Life-threatening Edwardsiella tarda soft-tissue infection associated with catfish puncture wound. PMID- 2230282 TI - Detection of potentially diagnostic leishmanial antigens by western blot analysis of sera from patients with kala-azar or multilesional cutaneous leishmaniasis. PMID- 2230283 TI - The architecture of bone marrow cell populations. AB - Marrow is a loosely bound tissue in which hemopoiesis has frequently been considered to be randomly distributed. The case is presented, however, for an organized and structured marrow in which close relationships exist between hemopoietic tissue and a regulatory microenvironment. Distributions of myeloid cells in the mouse femur are described, and a dynamic picture of their movement, with differentiation and maturation from the endosteal surface of the bone to their release via the central venous sinus, is painted. It is also shown that this structure is established within three weeks of birth. By contrast, mature lymphoid cells (but not their progenitors) are uniformly distributed. Regulatory stromal elements in the marrow are also structured and their localization is found to correspond closely to the properties of the progenitor populations. Such structure has potential practical importance, particularly in the field of medical, industrial or accidental radiation exposure where bone may introduce non uniform dose distributions in the marrow. PMID- 2230284 TI - In vivo toxicity of 3'-azido-3'-deoxythymidine (AZT) on CBA/Ca mice. AB - CBA/Ca male mice were given 3'-azido-3'-deoxythymidine (AZT) in drinking water (1 mg/ml) for up to 7 weeks. Water consumption and body weight decreased significantly. Neutropenia and lymphopenia were observed during and after exposure. Significant macrocytic anemia developed and disappeared as a function of red cell life span after stopping AZT intake. A microthrombocytosis was seen. Bone marrow cellularity and spleen colony-forming unit (CFU-s) content fell, but recovered completely and quickly after terminating AZT intake. Hemopoietic stem cell function measured by 2 different methods of rescuing fatally irradiated mice was normal 4 weeks after AZT exposure, suggesting that AZT treatment does not induce a long-lasting effect in genetic control of mitotic potential of stem cells. This is in marked contrast to exposure of CBA/Ca mice to benzene and ionizing radiation. PMID- 2230286 TI - Inhibition of hematopoietic progenitor colony growth by a monoclonal antibody against the transferrin receptor: comparison of unconjugated antibody with an immunotoxin containing recombinant ricin A chain. AB - We studied an immunotoxin consisting of recombinant ricin A chain (rRA) conjugated to 454A12 MoAb, a monoclonal antibody which recognizes an epitope on the human transferrin receptor, and compared the ability of 454A12 MoAb-rRA immunotoxin to inhibit the growth of erythroid burst-forming units (BFU-e) and myeloid colony-forming units (CFU-c) with unconjugated 454A12 MoAb. A significant reduction in BFU-e colony growth was observed at 0.001 microgram/ml of 454A12 MoAb-rRA versus 0.1 microgram/ml of unconjugated 454A12 MoAb (p = 0.005). Comparison of the effects of 454A12 MoAb-rRA and 454A12 MoAb on myeloid colony development gave markedly different results. Unconjugated antibody had no effect on CFU-c colony growth; in contrast, 0.01 microgram/ml of 454A12 MoAb-rRA reduced the number of colonies from 139 per 1 X 10(5) to 75 per 1 X 10(5) cells plated (p = 0.0005). No myeloid progenitor colonies developed at 0.1 microgram/ml of immunotoxin. These observations suggest that 454A12 MoAb-rRA inhibits growth by a potent, ricin A chain-mediated toxic effect on any proliferating cells expressing transferrin receptors, whereas the 454A12 MoAb exerts a selective inhibitory effect primarily on erythroid progenitors by perturbing the transferrin cycle. While growth factor receptors expressed on hematopoietic cells represent promising targets for immunotoxin therapy, our data indicate that an immunotoxin could inhibit cellular proliferation by a different mechanism than the corresponding unconjugated MoAb. Depending on the antibody used, these differences may be important in trials using immunotoxins for in vivo treatment or in vitro purging of malignant hematopoietic cells. PMID- 2230285 TI - Examination of survival, proliferation and cell surface antigen expression of human monocytes exposed to macrophage colony-stimulating factor (M-CSF). AB - The effects of macrophage colony-stimulating factor (M-CSF or CSF-1) on the survival, proliferation, maturation and activation of human blood monocytes were examined. M-CSF (100-1,000 U/ml) doubled the number of monocytes surviving after eight days in culture and accelerated the usual increase in cell volume. Antiserum to M-CSF abolished both of these effects. There was no sizable increase in 3H-thymidine incorporation in monocytes over this time period. Of various factors tested, including gamma-interferon (gamma-IFN), interleukin (IL) 1 alpha, granulocyte CSF (G-CSF), platelet-derived growth factor (PDGF), and lipopolysaccharide (LPS), only granulocyte-macrophage CSF (GM-CSF) could also enhance survival and augment cell volume. While antiserum to human M-CSF eliminated the increase in survival induced by GM-CSF, it could not ablate the GM CSF-stimulated increase in monocyte cell volume. Monocyte cell surface markers that increase with maturation (i.e., Fc gamma RIII) or with activation (i.e., Fc gamma RI) were unaffected by incubation with M-CSF. PMID- 2230288 TI - On syngeneic GVHD. PMID- 2230287 TI - The effect of carbamylcholine on CFU-s differentiation. AB - The proportion of spleen colony-forming units (CFU-s) killed by hydroxyurea was greatly increased after bone marrow cells (BMCs) from LACA mice were exposed to carbamylcholine (Cach; 1 X 10(-13) to 1 X 10(-9) in vitro and there was a marked change in the proportion of spleen colony types. Following treatment with Cach, granulocytic and mixed erythroid-type colonies increased from 20 to 26.3% and 16.1 to 29.6% in 9-day colonies and from 8.3 to 28.2% and 21.7 to 39.4% in 13-day colonies, respectively. Single cell suspensions of spleen colonies were made for granulocyte-macrophage progenitor (CFU-gm) and late erythroid progenitor (CFU-e) assays. The number of CFU-gm from Cach-treated BMC was about twice that from control BMC for both day 9 and day 13 groups; the number of CFU-e decreased relatively. The results suggest that cholinergic receptors on CFU-s may increase the tendency to differentiate into the granulocytic/monocytic line. PMID- 2230289 TI - Comparison of digital and cine coronary arteriography. AB - Digital coronary arteriography has advanced from a curiosity to a powerful clinical tool. This development has been motivated by the new imaging demands of interventional cardiology, by the need for quantifying atherosclerotic disease, and by advances in computer and video technology. Digital imaging has now essentially replaced cinefilm for clinical decision making in some catheterization laboratories, although uncertainty remains regarding the diagnostic comparability of the two modalities. Therefore, we compared simultaneously acquired digital and cine arteriograms from 18 patients with multivessel coronary artery disease. Digital utilized pulse-progressive technique, a 512 x 512 pixel x 8 bit image matrix, and no post processing. Four angiographers interpreted the arteriograms, identifying 131 stenotic lesions for measurement with manual calipers. Measurements of percent diameter stenosis by digital and cine correlated closely (r = 0.88), but digital estimated stenoses to be significantly more severe than cine (p less than 0.0001). This difference was most significant in small (less than 2 mm diameter) arteries, in branch arteries, and with mild stenoses. The differences between digital and cine were not statistically significant for stenoses greater than 50% diameter narrowing. Interobserver variability was similar for digital and cine imaging. Thus, unprocessed digital and film-based coronary arteriography yield similar assessments of atherosclerotic stenoses, but the techniques may not be diagnostically interchangeable. This paper discusses the technical advances which have occurred in digital coronary arteriography, the comparability of digital and cine imaging, and the factors which may be responsible for observed differences between the two modalities. PMID- 2230290 TI - Reproducibility of measurements of coronary narrowings by videodensitometry: unreliability of single view measurements. AB - Computer-assisted videodensitometry has been shown to be a reliable and reproducible method of measuring absolute and relative coronary narrowings. Using a commercially available analyzer (Vanguard XR70) we confirmed the intra- and interobserver reproducibilities in 34 narrowings in 9 patients. Analyses were performed on normal area and diameter, stenotic area and diameter, percent area stenosis and percent diameter stenosis. For all 6 analyses, excellent intra- and interobserver correlations were found (r = 0.93-0.98), with slopes close to 1 and intercepts close to zero. In a separate study of 16 lesions in 11 patients, each lesion was analyzed in both the RAO and LAO planes. Correlation between the measurements was reasonable with r = 0.76 for the stenotic area and r = 0.75 for the absolute diameter stenosis. However, with suboptimal slopes (0.54 and 0.63 respectively), actual differences between measurements in the two planes were often unacceptably large. These data suggest that videodensitometry is a highly reproducible quantitative angiographic method; however, single view analyses are inadequate for comparative studies. PMID- 2230291 TI - Three-dimensional reconstruction of stenosed coronary artery segments with assessment of the flow impedance. AB - In this paper preliminary results of a study about the diagnostic benefits of 3D visualization and quantitation of stenosed coronary artery segments are presented. As is well known, even biplane angiographic images do not provide enough information for binary reconstruction. Therefore, a priori information about the slice to be reconstructed must be incorporated into the reconstruction algorithm. One approach is to assume a circular cross-section of the coronary artery. Hence, the diameter is estimated from the contours of the vessels in both projections. Another approach is to search for a solution of the reconstruction problem close to the previously reconstructed adjacent slice. In this paper we follow the first method based on contour information. The reconstructed coronary segment is visualized in three dimensions. Based on the obtained geometry of the obstruction the pertinent blood flow impedance is estimated on the basis of fluid dynamic principles. The results of applying the reconstruction algorithms to clinical coronary biplane exposure are presented with an indication of the assessed flow impedance. PMID- 2230292 TI - An expert system for the labeling and 3D reconstruction of the coronary arteries from two projections. AB - In this paper we present a rule-based expert system for the automatic delineation and 3D reconstruction of the left coronary artery on standard RAO and LAO angiographic projections. The approach is based on the application of a general blood vessel model and on anatomical models which take into account the normal variations of the coronary artery structure. In a first step, the arteries are delineated by detecting the maximum intensity on the centerline of the vessels. Then, we label the blood vessel segments according to an anatomical model of the left coronary artery. In general, only 1-2 labels remain for each blood vessel segment. Finally, these results are used for an automatic 3D reconstruction of the left coronary artery from two projections. Results from clinical RAO and LAO angiograms will be presented. PMID- 2230293 TI - Restenosis following coronary angioplasty. AB - The assessment of restenosis following angioplasty has become increasingly important in determining the clinical value of the procedure. Despite this there has been no uniformly accepted methodology for assessing the procedure and consequently the published results have often been misleading with little concensus. In this paper some of the irregularities are documented and practical ways for adapting methodology proposed. PMID- 2230294 TI - Arterial stenting with self-expandable and balloon-expandable endoprostheses. AB - Coronary angioplasty is complicated by acute occlusion (within 24 hours) and late restenosis (within 6 months) in 2-5% and 20-40% of the cases, respectively. Vascular endoprostheses (stents) may provide the cardiologist with a solution to some of these complications. Several stent-devices are now available for experimental and clinical evaluation. In this study we describe our experience with two metallic stents in normal arteries of swine. Self-expandable, stainless steel stents (3.5 mm diameter) were implanted in 17 peripheral arteries, eight of which were deendothelialized by prior balloon angioplasty. Following implantation, the animals received antithrombotic therapy with acenocoumarol and aspirin (8 stents), or aspirin alone (9 stents). After 1 week repeat angiography was performed, which showed patency of all stented arteries. Microscopy showed complete covering by neointima, 80 microns in thickness. This self-expandable stent (SES) and a balloon-expandable stent (BES), constructed of tantalum, were implanted in normal coronary arteries. SES (3.0 and 3.5 mm) receiving animals were treated with coumadines (10 stents) or received no antithrombotic treatment (16 stents) after implantation. BES receiving animals were also not treated (10 stents). Three untreated animals with SES died suddenly within 48 hours. Postmortem examination showed partial or complete thrombosis of all six stents in these animals, resulting in a patency rate of 62% after 1 week. All animals with SES, which were treated with coumadines, and all animals with BES (untreated) had patent stents after one week. It is concluded that SES implanted in normal coronary arteries of pigs, which do not receive additional antithrombotic treatment, show a 38% occlusion rate within 48 hours, but show 100% patency after 1 week, when the animals are treated with coumadines. BES implanted in normal coronary arteries of pigs, which do not receive antithrombotic drugs, are 100% patent after 1 week. PMID- 2230295 TI - Pulsatile coronary flow determination by digital angiography. AB - A new angiographic method to calculate absolute coronary arterial blood flow and its cyclic variations as a function of time, has been designed and evaluated. The method combines densitometric analysis of spatial and temporal aspects concerning the contrast propagation through the arterial system from digital images, and is based on applying the concept of conservation of contrast material in successive images. It requires a standard arteriographic procedure. In simulations with both constant as well as pulsatile flow through a coronary arterial phantom, an excellent agreement with electromagnetic flow measurements was demonstrated (r = 0.993 and r = 0.982, respectively). Preliminary clinical results show, that the method yields reproducible assessment of coronary flow patterns after repeated injections in a patient. In a coronary artery bypass graft, coronary flow patterns in a baseline and a drug-induced hyperemic state were obtained. A consistent coronary flow reserve value was determined after repeated examinations. The method has been shown to be feasible in clinical applications, uncomplicated and fast, but requires further animal and clinical validation in order to determine the possible applications, limitations and accuracy. PMID- 2230296 TI - Mean transit time for videodensitometric assessment of myocardial perfusion and the concept of maximal flow ratio: a validation study in the intact dog and a pilot study in man. AB - Over the last decade it has become more and more obvious that besides anatomical information about the severity of coronary artery stenoses, information about coronary and myocardial blood flow is necessary to understand the functional significance of these obstructions and to evaluate the result of an intervention. Several methods have been proposed for this purpose, each of these having their particular limitations. In this study a new method is shortly described which allows the accurate calculation of relative maximal myocardial perfusion by ECG triggered digital radiography (videodensitometry), using mean transit time (Tmn) as time parameter; this technique is based on the original physiologic principles of indicator dilution theory. This method was validated in 8 instrumented dogs in which an excellent linear relation was present between 1/Tmn and flow (r = 0.96 +/- 0.03). Although this method does not allow assessment of resting flow and therefore coronary flow reserve (CFR), it provides a means for the reliable comparison of maximal myocardial flow in different situations and it is independent of most factors affecting coronary flow reserve. The ratio between maximal flow after and before an intervention is called maximal flow ratio (MFR) and this concept was applied in a pilot study in man to evaluate PTCA results in 10 patients undergoing elective angioplasty. MFR was compared with the result of exercise testing 24 hours before and 10 days after the angioplasty. MFR greater than or equal to 1.5 was always accompanied by reversal of exercise test result from positive to negative. We conclude that the accurate calculation of relative maximal perfusion of the myocardium is possible by videodensitometry and suggest that comparison of maximal flow after and before an intervention can be valuable in man for functional evaluation of the result of the intervention. PMID- 2230297 TI - Comparison of three different principles in the assessment of coronary flow reserve from digital angiograms. AB - In 70 patients without coronary disease we have compared three different principles to assess coronary flow reserve during diagnostic heart catheterization. Digital angiograms with ECG-triggered bolus injections of 4 to 8 ml of contrast medium at rest and after stimulation by dipyridamole (0,5 mg/kg i.v.) or papaverine (12,5 mg i.c.) were acquired in a 512 x 512 matrix at 8 bit resolution (ADAC 4100) and stored on a digital disk at 25 frames/sec. or 2 frames/cardiac cycle (PPR-mode). Angiograms were processed by cyclic R-wave-gated mask mode subtraction and coronary flow in the LAD area was assessed by three different approaches: 1. A traditional densitometric principle. 2. The 'CMAP' principle. 3. A modification of the Stewart-Hamilton principle comparing the total amount of contrast medium that enters the coronary circulation to the area of the contrast dilution curve in a fixed portion of the LAD. Flow was measured simultaneously during angiography using the thermodilution technique for coronary sinus/great cardiac vein flow. Drug stimulation resulted in an increased coronary blood flow up to five times of resting flow. Regression analysis revealed the following results for the assessment of the coronary flow reserved by digital angiography (y) when compared to thermodilution (x): [table: see text] Method 2 could be improved by replacing the density factor by morphometrically measured proximal LAD volume (y = 0.77x + 0.55; r = 0.78; SEE = +/- 0.43). In conclusion, our data suggest that the Stewart-Hamilton principle may be advantageous over time parameter-dependent approaches in the assessment of coronary flow reserve by digital angiography. PMID- 2230298 TI - Developments towards the slice-wise three-dimensional reconstruction of the distribution of the contrast perfusion in the myocardial muscle from biplane angiographic views. AB - In theory, radiographic myocardial perfusion imaging allows a quantitative assessment of the functional significance of a coronary stenosis. However, in the conventional two-dimensional projection images there does not exist a one-two-one relationship between a selected myocardial region of interest (ROI) and one particular coronary segment perfusing that area due to over-projection of myocardial regions in front of and behind the selected ROI perfused by other arterial segments, which may result in measurements which are difficult to interpret or even unreliable. To overcome these problems, we have developed two algorithms to determine the spatial distribution of perfusion levels in slices of the heart, selected approximately perpendicular to the left ventricular long axis, from two orthogonal angiographic views: the Segmental Reconstruction Technique (SRT) and the Network Programming Reconstruction Technique (NPRT). Both techniques require a priori geometric information about the myocardium, which can be obtained from the epicardial coronary tree (epicardial boundaries) and the left ventricular lumen (endocardial boundaries). Using the SRT approach, pie shaped segments are defined for each slice within the myocardial geometric constraints such that superimposition of these segments when projected in orthogonal biplane views is minimal. The reconstruction process uses a model with identical myocardial geometry and definition of segments. Each segment of the model is assigned a relative perfusion level with unit one if no other a priori information is available. In this case, the model contains geometric information only. In case a priori information about expected segmental perfusion levels is available, a level between zero and one is assigned to each segment. The a priori information on the myocardial perfusion levels can be extracted from either anatomic information about the location and severity of existing coronary arterial obstructions, or from a slice adjacent to the one under reconstruction. Using the NPRT approach perfusion levels are computed for each volume picture element of a slice within the reconstructed myocardial geometry, thus resulting in a much higher spatial resolution than the SRT approach. A priori information of perfusion levels must be included in this approach, again based upon anatomical information, or upon the slice adjacent to the one under reconstruction. The very first slice of a myocardial study will be reconstructed by the SRT approach. Extensive computer simulations for the SRT have proved that the mean difference between the actual and reconstructed segmental perfusion levels, on a scale from 0 to 1, is smaller than 0.45 (SEE = 0.0033, REE = 1.80) for various coronary artery disease states without the use of a priori information on expected perfusion levels. This error becomes smaller than 0.36 (SEE = 0.0026, REE = 1.42), if a priori information in the reconstruction technique is included. Similar computer simulations for the NPRT have proved that these mean differences in geometric segments equal to those defined for the SRT, are smaller than 2.94 (SEE = 0.0308, REE = 0.77) on a scale from 0 to 16, without the use of a priori information on expected perfusion levels, and smaller than 1.72 (SEE = 0.0304, REE = 1.10) on the same scale when a priori information is included. Therefore, it may be concluded that slice-wise three-dimensional reconstruction of perfusion levels is feasible from biplane computer-simulated data, and that a similarity exists for mean perfusion levels in corresponding regions in the simulated and reconstructed slices, for various states of single coronary artery disease. PMID- 2230299 TI - A new approach for the automated definition of path lines in digitized coronary angiograms. AB - For the quantitative analysis of a coronary segment from a coronary (cine)angiogram, an initial path line is required which functions as a model for the subsequent automated contour detection. For on-line applications, a new method for the automated definition of arterial path lines has been developed. Required user-interaction consists of the manual definition of a beginning and an endpoint of the arterial segment to be analyzed. The method is based on a combination of a beam tracer and a box technique. A validation study was performed on 47 non obstructed arteries of various lengths and diameters, and on 56 arterial segments with obstructions (up to 86 percent diameter stenosis). In 89% of the cases an acceptable path line was found after the first iteration; the success score increased to 99%, if a simple manual correction was allowed (2 iterations). The method is extremely fast: the overall average search time for the first iteration was 266 ms, for the second iteration 211 ms. Therefore, it may be concluded that this new technique for the automated definition of arterial path lines is extremely suitable for on-line applications. PMID- 2230300 TI - An objective computer system for the quantification of artery stenoses. AB - We have developed a low cost, clinically usable system for the objective assessment of the severity of coronary artery stenoses from single view angiograms. The system is based on a desktop computer with incorporated frame grabber. Images are captured by means of a video camera. The user selects a region of interest which encompasses the stenosis. Facilities are provided for automatic or manual definition of the artery centre line and edges. The computer then calculates the artery diameter and cross-sectional area by videodensitometry along profile lines which are orthogonal to the long axis of the artery. These results can be expressed numerically as a percentage stenosis when compared to a normal region of the artery. The image is corrected for geometric distortion using a grid test object. The image grey scale is corrected by means of a ramp test object such that a pixel value is proportional to the attenuator thickness. The ramp is placed on the patient during the X-ray examination and an iterative technique has been developed for subtracting the underlying structures from the superimposed ramp image. The system has been assessed using test objects constructed in Perspex which simulate arteries of known cross-sectional area and stenoses of known severity. PMID- 2230301 TI - Validation of a new automatic system for biplane quantitative coronary arteriography. AB - In a collaboration between the University of Texas (software) and the University of Zurich (hardware) a compact, automatic system for biplane quantitative coronary arteriography was developed. The system is based on a 35 mm film projector, a slow-scan CCD-camera (image digitizing) and a computer workstation (Apollo DN 3000, image storage and processing). A new calibration procedure based on two fixed reference points in the center of the image intensifier was used (isocenter technique). Contour detection of coronary arteries was carried out in biplane projection using a geometric-densitometric edge-detection algorithm. The proximal and distal luminal areas, as well as the minimal luminal area of the stenotic vessel segment were determined. Accuracy and precision were determined from precision drilled holes in a plexiglas cube which were filled with 50%, 75% and 100% contrast medium. The diameter of the holes ranged from 0.5 to 5.0 mm. The mean difference and the standard deviation of the differences between the true and the measured diameters were 0.12 +/- 0.14 mm for plane A and 0.26 +/- 0.17 mm for plane B, respectively. After a second order correction the mean difference amounted to 0.02 +/- 0.09 mm for plane A and 0.02 +/- 0.12 mm for plane B, respectively. Intra- and interobserver variability were evaluated in 5 patients (age 60 +/- 10 years) with coronary artery disease using 16 normal and 5 stenotic vessel segments (cross-sectional area ranging from 0.8 to 8.7 mm2). Two independent observers analyzed the same vessel segment twice. Intraobserver variability expressed as the standard error of estimate in percent of the mean angiographic vessel area (SEE) amounted to 2.1% for observer 1 and 4.4% for observer 2, respectively. Interobserver variability expressed as SEE was 4.1% for measurement 1 and 3.6% for measurement 2, respectively. PMID- 2230302 TI - Effects of video frame averaging, smoothing and edge enhancement on the accuracy and precision of quantitative coronary arteriography. AB - Digital analysis of cine film provides numerous options for altering images by frame averaging or filtering algorithms that either smooth or enhance edges. While these may subjectively enhance image quality, there is no uniformity in their use among laboratories and effects on quantitative coronary analysis may not be ideal. To determine which processing algorithms might help or hinder quantitative coronary arteriography, cine film images of precision drilled stenotic cylinders (0.83 to 1.83 nm diameter) implanted in dog coronary arteries were analyzed with and without such algorithms. Video frame averaging of 1 to 49 frames had no effect on measures of accuracy (mean differences) but precision (standard deviation of mean differences) was improved from 0.23 to 0.17 mm (p less than 0.05) with video averaging of greater than or equal to 25 frames. Edge enhancement filtering algorithms resulted in slight deterioration of accuracy and precision and smoothing filtering algorithms caused modest improvements in these parameters; however, these changes were not significantly different from unprocessed images. Using edge enhancement filtering algorithms, accuracy was significantly worse (-0.27 mm) compared to a smoothing filter enhancement algorithm (-0.08 mm, p less than 0.001). The combination of video averaging and smoothing algorithms had no additional beneficial effects. Thus, precision of quantitative coronary analysis of cine film can be optimized by appropriate video averaging. Edge enhancement filtering algorithms should be avoided whereas smoothing filter enhancement algorithms may improve accuracy. PMID- 2230303 TI - Aortic valvuloplasty of calcific aortic stenosis with monofoil and trefoil balloon catheters: practical considerations. An evaluation of balloon design and valvular morphology relationship, derived from experimental and clinicopathological observations. AB - In order to evaluate the relation between balloon design (monofoil, trefoil) and valvular configuration, experimental aortic valvuloplasty was performed in four post-mortem hearts with calcific aortic stenosis of various morphology. The degree of obstruction of the aortic orifice was assessed by computed axial tomography during inflation of monofoil 15 and 19 mm and trefoil 3 x 12 mm balloon catheters. We also evaluated the hemodynamic repercussion of balloon inflation (fall in systolic aortic pressure) in four elderly patients with acquired aortic stenosis who underwent a percutaneous transluminal aortic balloon valvuloplasty, with stepwise increasing balloon sizes of 15 mm, 19 mm and 3 x 12 mm, as during our in vitro experiments, and who underwent aortic valve replacement later on. In these patients, we correlated the anatomy of the excised aortic valves with the retrospective analysis of aortic pressure curves recorded during previous valvuloplasty procedures. Our experimental and clinicopathological observations showed that the degree of obstruction of the aortic orifice in post-mortem specimens and the tolerance to balloon inflation in live patients are dependent of the valvular configuration. Although trefoil balloons have the theoretical advantage to avoid complete obstruction of the aortic orifice during inflation, we observed that in presence of a tricuspid configuration, they could be potentially more occlusive than monofoil balloons since each of the 3 individual components of the trefoil balloon occupied the intercommissural spaces while inflated. However, they offered more residual free space when inflated in aortic valves with a bicuspid configuration (i.e. congenitally bicuspid valves or tricuspid valves with one fused commissure). In our opinion, these observations are relevant, since degenerative disease of the aortic valve (i.e. tricuspid valve without commissural fusion) is now recognized as the most common etiology of aortic stenosis in the elderly. PMID- 2230304 TI - High compression of nuclear medicine dynamic studies. AB - As data compression plays now an important role in the development of medical PACS, a technique has been developed for medical image sequences storage and transmission in order to obtain very high compression ratio: in dynamic nuclear medicine studies it can achieve a compression ratio as high as 100:1 without significant degradation. The implemented technique combines two methods which multiply their effects. In a first step, a principal component analysis (PCA) of the image series is performed. It extracts a limited number of principal components and their associated images. For data compression it is not necessary to perform an oblique factor analysis to estimate the so-called 'physiological functions' and their spatial distributions as in factor analysis of dynamic structures (FADS). In a second step, the principal images are compressed by means of a transform coding procedure: an adaptive block-quantization technique using the 2D discrete cosine transform (DCT) is implemented, followed by a statistical quantization method to encode the DCT coefficients. To reconstruct the principal images, an inverse DCT is applied. Then the original series is computed from the reconstructed images combined with the principal components which have been stored without any modification. The reconstructed series is compared to the original series, as well as the time activity curves generated on different regions of interest (ROI) and the factor estimates obtained using FADS performed on the two series. Method and evaluation are illustrated on an example of first pass radionuclide angiocardiography. PMID- 2230305 TI - Transesophageal echocardiography after orthotopic heart transplantation. PMID- 2230306 TI - Human fascioliasis: T cell subsets in liver before and after bithionol treatment. AB - Liver biopsies from 5 patients with established fascioliasis, before and after bithionol treatment were studied by immunoalkaline phosphatase technique for relative distribution of T cells and their subpopulations. T cell and its subsets are defined for OKT3+ (pan T), OKT4+ (helper/inducer) and OKT8+ (suppressor/cytotoxic) cells by using mouse monoclonal antibodies. Before bithionol treatment, lymphocytic infiltration in all hepatic lesions were predominantly of OKT3+ (pan T) lymphocytes. The distribution of OKT8+ cells was moderate to severe in comparison to the few OKT4+ cells presentation. After bithionol a noticeable regression of the OKT3 lymphocytic in all liver sections. The majority of the lymphocytic infiltration was of the OKT8+ cells, in comparison to the absence of the OKT4+ ones. This may indicate that suppressor/cytotoxic lymphocytes may have a role in the immune regulation of the disease and the mode of action of bithionol is by the accentuation of this immunoregulatory effect. PMID- 2230307 TI - Circulating E. histolytica antigens clear with successful treatment of amoebic liver abscess. AB - An antigen capture ELISA was used to measure serum E. histolytica antigen and antibody levels in 23 patients with amebic liver abscess (ALA), 15 patients with intestinal amebic infections (IAI), and 20 normal controls. 16 of the 23 (70%) with ALA had antigenemia. None of those with IAI or the normal controls had E. histolytica antigen titers of greater than 1:4. All 23 of the patients with ALA had positive antibody titers. Three (20%) with IAI and none of the normal controls had E. histolytica antibody titers greater than 1:100. Antigenemia cleared in all but one of the 23 patients within two months of initiating successful chemotherapy. Antibody titers were much slower to diminish. Measuring E. histolytica antigens in the sera of patients with ALA by increasing the diagnostic specificity may have some diagnostic advantage over measuring only the antibody levels. In addition, serial measurements of antigenemia are useful in monitoring result following chemotherapy. PMID- 2230308 TI - Human fascioliasis: ultrastructural study on the liver before and after bithionol treatment. AB - The pathology of human fascioliasis was studied before and after bithionol treatment using light and transmission electron microscopy. Fine needle biopsies were taken from five patients, with established fascioliasis, before and after drug administration. By light microscope the pathology of human fascioliasis was similar to that reported in experimental fascioliasis. The ultrastructural picture revealed bile ductular hyperplasia, fibrosis of portal tracts, widening of the interhepatic spaces by many microvilli and dilated Disse space with collagen fibres. Bile ductular hyperplasia may be the initial factor to fibrinogenesis, which subsequently enhance the development of the microvilli on the surface of the hepatocytes. Both light and electron microscopic studies revealed regression of the picture of fascioliasis to normal after bithionol treatment with no sign of toxicity on the liver. PMID- 2230309 TI - Pathologic examination of the placenta in human cases of toxoplasmosis. AB - One hundred sixty one placentae were examined grossly and microscopically, 131 specimens belonged to seropositive patients and 30 specimens belonged to seronegative patients and used as control. 63.3% of the placentae of seropositive patients were macroscopically normal, 9% were hydropic, 21% were of mixed or partially hydropic pattern, 6% had areas of infarction & 0.7% showed areas of calcifications. The most consistent microscopic finding was focal low grade chronic villitis with mononuclear inflammatory infiltrate. In hydropic placentae villous edema was of very variable degree from one placenta to another and from one area to another in the same placenta. Nucleated red blood cells were demonstrated in villous capillaries. The patients had Rh positive factor in their blood. PMID- 2230310 TI - Evaluation of gastric carcinoembryonic antigen in endemic schistosomal hepatosplenomegaly. AB - In endemic hepatosplenomegaly with histopathologically proved atrophic gastritis, the gastric juice carcinoembryonic antigen (CEA) showed significant increase. Comparing this group of patients with histopathologically proved gastric neoplasia the levels were significantly higher in the later group. The level of (CEA) was only increased in 75% of cases with endemic hepatosplenomegaly and atrophic gastritis opposite to 100% of cases with gastric neoplasia. The level of serum (CEA) was also studied in patients and control groups. In patients with endemic hepatosplenomegaly and atrophic gastritis the level was insignificantly higher than the control group and significantly lower than the group with gastric neoplasia. PMID- 2230311 TI - Studies on gastric bacterial growth and gastric PH in endemic schistosomal hepatosplenomegaly. AB - Acid content and bacterial flora were studied in the gastric juice of 30 patients with endemic hepatosplenomegaly and 10 normal controls. The acid content in the gastric juice was significantly low in the group of patients. Also the bacterial flora were present in larger number of patients (80%) opposite to (30%) in normal control group. PMID- 2230312 TI - Histocompatibility (HLA) antigens in Egyptians with two parasitic skin diseases (scabies and leishmaniasis). AB - The frequency of human leucocytic antigens (HLA) were studied in 62 patients with scabies and 27 patients with cutaneous leishmaniasis to evaluate the role of HLA antigens as genetic markers in the pathogenesis of these parasitic skin diseases. A significant statistical association was proved between HLA-A11 antigen and scabies and between HLA-A11, -B5 and -B7 antigens and diffuse cutaneous leishmaniasis. PMID- 2230313 TI - Evaluation of immunodiagnostic tests in detection of trichinosis in experimentally infected rats. AB - The enzyme-linked immunosorbent assay (ELISA), the indirect immunofluorescent (IF) and the counter current immunoelectrophoresis (CEP) were evaluated in detection of anti-Trichinella antibodies in experimentally infected rats. The CEP was the most specific and highly sensitive test. Also, the IF was highly sensitive but less specific. ELISA was the least specific but extremely sensitive specially in detecting early infection. PMID- 2230314 TI - Ultra structure study of schistosomula recovered after cercarial penetration of isolated skin. AB - The ultrastructure, development and antigenic nature of the surface and the viability of schistosomula formed after cercariae had penetrated isolated skin has been studied. Within 2 hours of transformation, the surface membrane of schistosomula had changed from trilaminate to heptalaminate structures and lost their cercarial glycocalyx. The preacetabular glands of schistosomula were emptied, the mixed agglutination reaction demonstrated the presence of human A and B blood group-like antigenic determinant on approximately 30% of 3 hours old schistosomula. The first schistosomula reached the gut closed stage by day 12 (50 70%), and between 40% of all schistosomula developed to maturity when injected intravenously into mice. PMID- 2230315 TI - Distribution of Phlebotomus species in the Nile Delta, Egypt. AB - The importance of sandflies of the genus Phlebotomus being in the fact that some species are the vectors of leishmaniasis and other pathogenic organisms such as virus of sandfly fever. In Egypt, cutaneous leishmaniasis and sandfly fever are known and recently visceral leishmaniasis has been identified in Alexandria. Consequently, there is a need to study the geographical distribution of Phlebotomus species and to present an illustrative key for their identification. In the present study, four species of Phlebotomus were reported; P. papatasi, P. sergenti, P. langeroni and P. bergeroti. While P. papatasi is a known vector of zoonotic cutaneous leishmaniasis, P. langeroni is an incriminated vector for infantile visceral leishmaniasis, P. papatasi is the predominant species in the Nile Delta, but P. langeroni is found in West Alexandria and as a very rare species at the Libyan Egyptian borders. The whole results were discussed. PMID- 2230316 TI - The mechanism of acquired immunity in experimental giardiasis. AB - Giardia-spontaneously cured mice were rendered resistant to challenge infection. This was documented by the decreased cyst excretion rate comparable to the control ones. Endoxan and irradiation treatment caused a breakdown in both humoral and cellular immunity. Immune-depressed mice were more susceptible to Giardia infection, thus proving the active role of antibodies and cell-mediated immune response in giardiasis. PMID- 2230317 TI - The relation between intestinal troubles and parasitic infection in Cairo. AB - Stool and urine from 320 subjects in Ain shams region, and 200 subjects in Nasr city were collected and examined for parasites. All these subjects were suffering from abdominal troubles. The results revealed a marked relation between parasitic infection and abdominal troubles, especially in Ain shams region (80%), and to a lesser extent in Nasr City (51%). The commonest parasite in Ain shams was Giardia lamblia (20.3%), and in Nasr city was E. histolytica (13%). PMID- 2230318 TI - Immunization against experimental visceral toxocariasis canis. AB - Immunization of rabbits against visceral toxocariasis using T. canis larval glycoproteins showed a marked reduction in the larvae burden and a significant rise of serum IgE in immunized rabbits infected with Toxocara canis as compared with non-immunized infected control group. More reduction of larval burden was observed after larger doses of T. canis larvated eggs inoculation. PMID- 2230319 TI - Detection of Giardia lamblia copro-antigens by enzyme-linked immunosorbent assay and counterimmunoelectrophoresis. AB - The enzyme-linked immunosorbent assay (ELISA) and counter-immunoelectrophoresis (CIEP) were used to detect G. Lamblia Copro-antigens. Rabbit antisera raised against Giardia trophozoites and cysts were used as anti-Giardia antibodies. The overall sensitivity of the ELISA was 96.15% and its specificity was 93.48% in contrast to 69.23% and 82.61% for the CIEP. PMID- 2230320 TI - Virulence of Giardia lamblia isolates to laboratory mice. AB - Laboratory breed albino mice free of G. muris infection were inoculated with G. lamblia cysts isolated from the stools of patients with different clinical manifestations, symptomatic diarrhoeic, symptomatic non-diarrhoeic and asymptomatic cyst carriers. The virulence of various isolates was assessed by cyst excretion rate in the stools, trophozoite counts in the duodenum and histopathological lesions of jejunal mucosa. A marked variation in the virulence of cysts obtained from the 3 groups of patients was proved. PMID- 2230321 TI - Fresh water malacologic fauna in Dakahlia Governorate. AB - Ten snail species representing the snail fauna in Dakahlia were identified as P. acuta, B. unicolor, L. carinatus, Cleopatra species, B. alexandrina, M. tuberculatus, H. duryi, B. truncatus, N. nilotica and L. caillaudi. The density of snail population has had a major peak at July and August while a minor peak was found at the winter closure period during the winter months. PMID- 2230322 TI - Histopathological and histochemical studies on experimentally infected hamsters with Stictodora tridactyla. AB - Histopathological changes in the intestinal mucosa in the form of inflammation with atrophic changes in the villi and foci of cellular reaction were seen at the sites of experimental infection in hamsters with Stictodora tridactyla. The activity of succinic dehydrogenase, non specific esterase and alkaline phosphatase enzymes in the villi and the activity of acid phosphatase in the glands were markedly reduced. These changes suggest a disturbance in both digestive and absorptive mechanisms of the small intestine. PMID- 2230323 TI - Placental villous maturation in patients with repeated abortions and chronic toxoplasmosis. AB - The conceptions products obtained from 20 patients with repeated abortions and chronic toxoplasmosis were examined histopathologically comparing the results with those of ten Toxoplasma seronegative patients. The results showed significant association between chronic toxoplasmosis and diffuse failure of growth of placental villi. PMID- 2230324 TI - Humoral and cellular immune response in schistosomiasis pre and post praziquantel therapy. AB - Humoral and cellular immune response in schistosomiasis was studied pre and post praziquantel therapy. After treatment the mean anti SEA IgM and IgG and anti SWAP IgM levels in all cases showed significant reduction. In patients with high eosinophilic count anti SEA IgE and IgA were statistically decreased. Other specific antibodies showed negligible changes Cellular immune response was not affected. PMID- 2230325 TI - ELISA in detection of Entamoeba histolytica antigens in stools. AB - The modified double antibody sandwich ELISA was applied to detect E. histolytica antigens in the stool samples of 20 patients have amoebiasis (symptomatic or asymptomatic), 10 with intestinal parasites other than E. histolytica and 10 healthy individuals. The method was found to be sensitive (90%) and specific (85%). It is concluded that ELISA could be applied for a large scale epidemiological study and immunodiagnosis of amoebiasis. PMID- 2230326 TI - Serological studies on toxoplasmosis in Zagazig slaughterhouse. AB - This study intended to estimate the prevalence of Toxoplasma antibodies among farm animals in Zagazig slaughterhouses using indirect haemagglutination test (I.H.A.T.) and to evaluate the occupational exposure to infected animals and meat among abattoir workers. 25% of the tested animals were seropositive 19.2% of the exposed persons showed positive reactions while in a control group it was 12% with statistically insignificant difference. PMID- 2230327 TI - The mode of inheritance of fenitrothion resistance in Culex pipiens L. larvae (Diptera:Culicidae). AB - The genetics of fenitrothion resistance in Cx. pipiens larvae was studied to determine its mode of inheritance. A laboratory susceptible and fenitrothion resistant larval strains were used. Reciprocal crosses between the resistant and susceptible strains showed an F1 generation of partial dominance with slight cytoplasmic effect. The F2 generation underwent segregation into three genotypes, viz. susceptible, hybrid and resistant in the ratio of 1:2:1. The progenies of backcrosses to resistant and susceptible parents were in a 1:1 ratio of the same phenotypes as the parents and hybrids involved. After selection, the progeny of the back-crosses to resistant parent exhibited full resistance. It is concluded that fenitrothion resistance in Cx. pipiens larvae is due to monofactorial inheritance with partial dominance and slight cytoplasmic effect. PMID- 2230328 TI - Studies on cutaneous leishmaniasis in Al-Kharaj area, Riyadh, Saudi Arabia. AB - A total of 600 patients with lesions of cutaneous leishmaniasis were diagnosed clinically as suffering from the disease; 138 (23%) were confirmed parasitologically for amastigote forms of L. major; promastigotes grown in culture were confirmed in 180 (30%) cases. Lesions varying in number and sites and the disease showed a high prevalence among non-Saudis (88%) labourers compared to Saudis (12%). Cutaneous leishmaniasis was found to vary seasonally with most cases reported during December to February. PMID- 2230329 TI - The course of Giardia muris infection in immunocompetent and immunocompromised mice. AB - No significant sex-related difference was observed in immunocompetent mice. Sexually mature mice of both sexes excreted large numbers of Giardia cysts over a longer period than did immature ones. Cyclosporin A has compromised the immunological response of the primary Giardia infection. However, it does not affect the ability of the immune host to resist challenge infection. The use of this drug may cause fulmination of giardiasis. PMID- 2230330 TI - Comparative study of the Sabin-Feldman dye test and the indirect haemagglutination test in serodiagnosis of toxoplasmosis. AB - 200 women with history of abortion and 100 women with history of uneventful pregnancies were investigated serologically for anti-Toxoplasma antibodies using both the indirect haemagglutination test and the Sabin-Feldman dye test. Our results indicated a role for the first test in seroepidemiological surveys and for routine work. The second test may be reserved for cases with negative haemagglutination test in the presence of strong suspicion of toxoplasmosis. PMID- 2230331 TI - Haematological changes observed in Swiss albino mice infected with normal and gamma-irradiated E. granulosus larvae. AB - Five groups of Swiss albino mice (Mus Musculus albinus) were intraperitoneally inoculated with 2,000 aseptic normal (control group) and gamma irradiated E. granulosus, larvae at different dose levels of 40 Kr, 60 Kr, 80 Kr and 100 Kr, respectively. Haematological studies showed a marked leucocytosis, a progressive increase in the average percentage of eosinophils as well as a great successive decrease in haemoglobin concentration through out the time of infection in control group as compared to the treated ones. Meanwhile the leucocytic count and the Haemoglobin concentration in treated mice was dose dependent as well as time dependent whereas the eosinophil percentage was only dose dependent rather than time dependent. PMID- 2230332 TI - The breeding habitats of Phlebotomus sand flies (Diptera:Psychodidae) in El Agamy, Alexandria Egypt. AB - A prolonged search for the breeding habitats of Phlebotomus sand flies in El Agamy, resulted in the collection of 105 newly emerged P. papatasi and P. langeroni. These flies were from poultry sheds, rubbish on stone piles and rubbish piles. PMID- 2230333 TI - Total count of microorganisms contaminating water supply system of Ismailia City, Egypt. AB - The efficiency of water purification in the French and the British systems of Ismailia city was evaluated concerning the contaminating microorganisms. Counting of microbial contaminants was based on the phenotypic characters of the colony type. Colony-types of eubacteria, eumycetes, Micromonospores and Streptomyces enumerated in the crude water and the different steps of purification. Total counts of microflora in both systems were higher than the counts in canal water. Meanwhile, microbial isolates were higher in the French system than that of the British one. The increased counts in tap water, compared with canal water, were recorded in winter for bacteria and in spring for fungi. These data showed variations in the microbial total counts according to: plant system, steps of purification, chlorination season and type of microbes. PMID- 2230334 TI - Antioxidant enzymes in Trichomonas vaginalis. AB - The activities of artificial donor peroxidase, catalase, and superoxide dismutase in clinical isolates of T. vaginalis were studied. None of the tested strains exhibited activity of the three enzymes. Inclusion of catalase in Diamond-TYM solid medium did not support growth under aerobic conditions. The correlation between the absence of these enzymes and the growth conditions of the organism is discussed. PMID- 2230335 TI - Animals as reservoir hosts for Leishmania in Qualyobia Governorate, Egypt. AB - A total of 239 rodents were collected from El-Khanka, Shebin El-Kanater, El Kanater, Shoubra El Khima, Qualiob, Tokh, Benha and Kafr-Shokr and identified as Mus musculus (30), Rattus rattus (78), Rattus norvegicus (35), Arvicanthus niloticus (62) and Acomys cahirinus (34). Examination of these rodents showed the presence of cutaneous lesions in two R. rattus, three R. norvegicus and one A. cahirinus which showed no Leishmania parasites neither by smear nor by culture. On examination of the liver, spleen and bone marrow parasitologically, the spleen of two R. norvegicus grew promastigotes, one was lost and the other was typed. Serological examination of rodents revealed antileishmanial antibodies in one A. niloticus and in two R. norvegicus by IHAT and in one R. rattus by Dot-ELISA. A total of 33 stray dogs trapped from El-Khanka Shebin El-Kanater and Qualiob were free from natural Leishmania infection as indicated clinically, parasitologically and serologically. PMID- 2230336 TI - Evaluation of some direct diagnostic methods in intestinal parasitic infections. AB - Stool specimens of 100 cases attending the outpatient clinic of Cairo Medical Center Hospital suffering from gastro-intestinal disturbances were examined for intestinal parasites by direct smear, trichrome stained smear and formol ethyl acetate concentration methods. Although formol ethyl acetate concentration method gave the best results (45%), followed by trichrome stain (37%) then direct smear (32%) yet, for a reliable diagnosis a combination of several techniques is required. PMID- 2230337 TI - Histopathological studies of acute, chronic and congenital infections of toxoplasmosis in mice. AB - The histopathological picture of Toxoplasma gondu RH strain (virulent) and Beverley strain (a virulent) was experimentally studied in mice. Nearly all the internal organs and tissues showed pathological changes ranging between the mild congestion to the severe degeneration. However, the changes were more serious in mice infected with RH strain than those infected with Beverley strain. The lungs showed massive consolidation and severe congestion. The heart showed hyaline degeneration of a cardiac muscle fibers. Focal areas of necrosis were seen in the liver, spleen and kidneys which were enlarged as well as in the cerebral cortex of the brain. The bone marrow and skeletal muscles were infiltrated by mononuclear inflammatory cells. The eyes showed mononuclear inflammatory cells in the retina consisted mainly of lymphocytes and the photo receptors were damaged. In congenital toxoplasmosis the brain showed perivascular mononuclear inflammatory infiltrate as well as multiple areas of necrosis. Microglial nodules were sometimes seen. The eyes showed no pathological lesion. PMID- 2230338 TI - Assessment of IgG & IgM, ELISA and IFAT in diagnosis of toxoplasmosis in pregnancies at risk. AB - This study was carried out on 100 pregnant cases, divided into 5 groups of patients having congenitally malformed newborns, suffering from stillbirths, premature labours, repeated abortions and control group. The incidence of positive Toxoplasma antibodies was higher in the congenital malformation and stillbirths groups than other groups. Analysis of the results showed that an excellent correlation exists between ELISA and IFAT with a minimal differences (less than 5%). PMID- 2230339 TI - Phase-contrast study of the efficacy of Lampit (BAY 2502, Nifurtimox) on experimental infection with Trypanosoma rhodesiense. AB - Lampit (BAY 2502, Nifurtimox) was tested in experimental Wistar strain white rats with acute infection induced by Trypanosoma rhodesiense strain (180 TS1A1), which normally contains cytoplasmic granules of both Type (I) & (II). Lampit injected subcutaneously in low doses of 25, 50, 100, and 250 mg/kg b-w as one-time application, gave no effect. When repeated higher doses (500 mg/kg b-w) was given a reasonable effect was achieved and formation of additional granules in T. rhodesiense was noticed. In experimental animals, some what higher initial doses appear to be particularly advantageous. PMID- 2230340 TI - Rodents and their ectoparasites in Sharkia Governorate, Egypt. AB - Rodents serve as reservoir hosts for many parasitic and bacterial diseases which are spread to man and animals by their habits, their droppings or by their arthropod ectoparasites. Commensal (semi-domestic) rodents were collected by different methods from Sharkia Governorate over a period of one year, 1989. The trapped rodents in descending order of prevalence were Rattus norvegicus, Rattus rattus, Mus musculus and Gerbillus gerbillus. The ectoparasites were collected and identified as five species of fleas, one species of lice and one species of mites. The role of these rodents as animal reservoirs and their ectoparasites as vectors of zoonotic diseases was discussed. PMID- 2230341 TI - Rheumatoid factor among several cases of visceral leishmaniasis. AB - Rheumatoid arthritis is not an uncommon disease in Egypt. Its aetiology is still unknown. In this paper, 3 out of 7 visceral leishmaniasis cases and 1 out of 7 controls gave positive rheumatoid factor. It was suggested that L. donovani infection plays a role in the aetiology of rheumatoid arthritis. PMID- 2230342 TI - Pattern of eosinophilia and muscle larval burdens in experimental trichinosis. AB - Absolute eosinophilic counts to different developmental stages of Trichinella spiralis in experimental trichinosis were studied to identify the stage responsible for eosinophilia. Two peaks of eosinophilia were noticed, the first (545 +/- 172.3) was attributed to the adult stage while the migrating larvae were accused to be responsible for the more pronounced second peak (1265 +/- 331.7). With encapsulation a steady raised level was demonstrated. Chromatographic studies to determine the nature of eosinophilogens produced by the different stages are recommended. The role of eosinophils in damaging the parasite is discussed in details. No correlation could be determined between muscle larval burden and eosinophilic count. PMID- 2230343 TI - Filariasis cross react in IHAT for leishmaniasis. PMID- 2230344 TI - Changes in anti-idiotype antibodies against anti-HBs during recombinant interferon treatment of chronic hepatitis B. AB - To determine the possible changes in the presence and level of anti-idiotype (anti-Id) antibodies against anti-HBs induced by recombinant interferon (rIFN) therapy in chronic hepatitis B virus (HBV) infection, a study of patients under rIFN treatment has been carried out. A total of 62 (38 treated and 24 controls), HBeAg and HBV-DNA positive HBsAg carriers were tested serially for the presence of IgG and IgM anti-Id antibodies. According to serological evolution, treated patients were divided in responders (HBeAg and HBV-DNA became negative) (n = 18) and nonresponders (n = 20). Control patients were also classified as having spontaneous seroconversion (n = 11) and without changes (n = 13). Basally all patients had IgG and IgM anti-Id. At the end of the follow-up period (15th month), a significant decrease was observed in the percentage of cases positive to anti-Id among rIFN-responders (IgG, 67%, p less than 0.01; IgM, 44%, p less than 0.001). In contrast, only one nonresponder lost IgM anti-Id during the study. Among controls, only one with spontaneous loss of HBV-DNA and HBeAg clearance became negative to both IgG and IgM anti-Id. In addition, in the basal sample, the rIFN-responders had significantly lower anti-Id levels than the nonresponders (p less than 0.05). Similar results were obtained when comparing the controls with or without spontaneous response (p less than 0.05). Furthermore, a significant decrease in the anti-Id levels among the rIFN responders at the 9th month was detected (p less than 0.01). In summary, the anti Id antibodies decreased significantly in patients who became HBV-DNA negative following rIFN administration. This result confirms the close relationship between HBV replication and the anti-idiotype against anti-HBs. PMID- 2230345 TI - Effects of prolonged exposure to interferon-alpha on the viability, proliferation, differentiation, and tumorigenicity of HL-60 promyelocytic leukemia cells. AB - HL-60 promyelocytic leukemia cells were cultured continuously in the presence of 22,000 IU/ml of purified interferon-alpha (IFN-alpha) for up to 469 days. Study of the properties of the cells at various times during this period showed some changes in their expression of IgG Fc receptors, and in the maturation of the cells as indicated by their esterase content. The differences from control cells cultured in parallel were most marked after exposure to IFN-alpha for some 40-300 days, but were no longer seen after 400-470 days. The difference in tumorigenicity was significant after 150 days, but no longer after 300 days. PMID- 2230346 TI - Distribution, kinetics and immunoscintigraphy of 131-I labelled intact antifibrinogen-fibrin antibody (AbFbg) and its F(ab')2 fragment. AB - 131-I-labelled anti fibrin-fibrinogen antibody (AbFbg) was compared with its F(ab')2 fragment in distribution studies and by immunoscintigraphy with a view to tumour visualization in tumour bearing rats. The distribution studies indicated that the intact antibody is more concentrated in tumour tissue than the F(ab')2 fragment. By 168h after injection, when tumour-to-tissue ratios were highest in the majority of tissues, the tumour concentration of intact antibody was 3 to 4 times that of the F(ab')2 fragment. The intact antibody is more suitable than the F(ab')2 fragment for tumour imaging especially in the abdominal region where the highest tumour-to tissue ratios were obtained with intact antibody in liver, spleen, intestines and kidneys. PMID- 2230347 TI - MCA in patients with breast cancer: correlation with CEA and CA15-3. AB - MCA serum levels were determined in 27 healthy subjects, 136 with benign pathology (42 breast) and in 289 patients with cancer (247 active). The last group includes 223 patients with breast cancer (96 without metastases, 89 with metastases and 38 no-evidence of disease). CEA and CA15-3 serum levels were determined in all the patients with breast diseases. The mean levels of MCA were 4.7 + 2.4 U/ml in the control group, considering less than 11 U/ml as normal. MCA values were abnormal in 15.4% of patients with benign pathology, mainly in those with liver cirrhosis (8/20) and lung diseases (4/20). In the majority of these cases, the rise was only moderate, lower than 15 U/ml in 97.5% of patients. In malignant diseases, important increments were found in breast cancer (19.8% Mo, 77.5% M1) and ovarian cancer stages III-IV (44.4%). When we compared MCA serum levels with CA15-3 and CEA in breast pathology, a similar specificity was observed: 92.3%, 92.3% and 100% in cases with benign pathology and 92.1%, 94.7%, and 97.4% in NED patients, respectively. MCA and CA15-3 sensitivity was similar in breast cancer without metastases (19.8%) and lower for CEA (16.7%). In patients with breast cancer without metastases, we found a relation between positivity of these tumor markers and prognostic factors (tumor size, nodal involvement). The disease free interval in patients with locoregional breast cancer was shorter in cases with abnormal presurgical levels of some of the tumor markers, but only the difference from MCA was significant (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230348 TI - Clinical evaluation of CA 15.3 in the post-operative follow-up of breast cancer patients. AB - In 265 patients operated for breast carcinoma the monoclonal antibody serum test CA 15.3 was predictive of metastatic diffusion of the disease. Its level increased in cases of distant metastasis with no significant difference between multiple and single sites (p = 0.014). The concentration of the marker was higher in 21 (23.8%) patients without nodal involvement and in 19 (27.5%) with nodal involvement (p = 0.193). Our study suggests that CA 15.3 may be an aid in the follow-up of patients with metastatic diffusion of breast cancer. PMID- 2230349 TI - Immunoreactive calcitonin: a tumor marker for myelogenous leukemias. AB - In a series of 59 patients with chronic or acute myelogenous leukemia (CML, AML) we investigated whether circulating immunoreactive human calcitonin (i-hCT) levels correlate with diagnosis, response to therapy and clinical course. I-hCT was detectable in plasma samples of 88% of patients with CML in the chronic phase and in 100% of patients with CML in blastic transformation. In the AML patients, a significant relation was observed between the cytological subtype and i-hCT levels at diagnosis. In sequentially studied patients the i-hCT plasma concentration was related to the overall mass of leukemic cells, being lower when complete remission was achieved than at diagnosis and increasing at time of recurrence. These data suggest that circulating i-hCT levels can serve as a "tumor marker" in human myelogenous leukemias. PMID- 2230351 TI - MCA and CA 15.3 serum levels in non-malignant diseases. Some preliminary results. PMID- 2230350 TI - Prognostic significance of CA 15.3 in metastatic breast cancer. AB - We have investigated the possible relation between serum levels of CA 15.3 and disease status in 110 patients after radical mastectomy for breast cancer, with metastatic diffusion. Its persistent elevation was usually related to a very poor prognosis. In patients who died within 18 months the marker was always elevated. In case of progression of the disease, the marker level appeared to be consistently correlated with the general clinical condition. In healthy patients with stable disease the marker remained near the normal range. PMID- 2230352 TI - Correlation between BCM (breast cancer mucin) and CA 549 serum levels cystic breast disease. PMID- 2230353 TI - Serum BCM levels in patients with non-tumoral pathologies: a value of 25 U/ml can be used as threshold for tumoral activity. PMID- 2230354 TI - Tumor markers in squamous cell carcinoma of esophagus: immunometric assay in cytosol and membrane fraction. AB - Carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), ferritin, and the monoclonal antibody-detected tumor-associated antigens CA19.9 and CA50 were measured by radioimmunoassay in tissue fractions of carcinoma and normal esophageal mucosa from 59 patients with untreated primary squamous cell carcinoma of the esophagus. Tumor markers were measured in cytosol (118 samples) and in a membrane-enriched fraction (32 samples). CEA, TPA and ferritin were detected in almost all the cytosol samples evaluated, CA19.9 and CA50 in 66% and 50% of cases respectively. Ferritin was significantly higher in carcinoma than in normal mucosa. The cytosol concentrations of CEA, TPA, CA19.9 and CA50 were not significantly different in carcinoma and normal tissue. Concentrations of CEA, CA19.9 and CA50 in the membrane fraction tended to be higher in normal tissue than in carcinoma, whereas the cytosol-to-membrane ratio was significantly higher in carcinoma. For CEA, CA19.9 and CA50, the phenotypic pattern of the malignant transformation seems to involve a different intracellular distribution rather than a quantitative change. No correlations were found between tissue and serum concentrations of the tumor markers, the former being related to the phenotypic characteristics of the tumor, the latter to the tumor burden. PMID- 2230355 TI - Different role of liver dysfunction and damage in increasing serum CA 19-9, TPA, and CEA in patients with pancreatic cancer. PMID- 2230356 TI - Carcinoma of the pancreas: problems of diagnosis and treatment in Africa. PMID- 2230357 TI - Pancreatic exocrine and endocrine function in patients with pancreas divisum and abdominal pain. AB - Pancreatic exocrine and endocrine function is described in 29 patients with pancreas divisum and upper abdominal pain. The diagnosis was made by endoscopic pancreatography (ERP) after cannulation of the major, as well as the accessory, papilla in all patients. At ERP, six patients had signs of marked and six patients moderate pancreatitis, whereas 17 patients were free from pancreatitis changes. Pancreatitis was found in the dorsal anlage in 12 patients (41%) of whom seven (24%) had similar alterations also in the ventral anlage. Fecal fat excretion was increased in 48% of the patients, and abnormal serum levels of pancreatic enzymes were found in more than one-third. Impaired insulin release was detected in 21% of the 28 patients examined following ingestion of oral glucose. Including an additional patient with manifest diabetes, 24% (7/29) had signs of endocrine insufficiency. The serum-insulin, serum-C-peptide and insulin/glucose pattern following an oral glucose load reflected the degree of severity of pancreatitis changes at ERP. Altogether, 66% of the patients had morphological and/or functional evidence of pancreatic affection. PMID- 2230358 TI - Plasma osmolality and exocrine pancreatic secretion. AB - To confirm the influence of plasma osmolality on exocrine pancreatic secretion, hypertonic saline (4% saline) was given intravenously to dogs with gastric and pancreatic fistulae. Intravenous administration of hypertonic saline caused a reduction of pancreatic juice flow and bicarbonate output, but did not alter protein output stimulated by secretin and cerulein. The changes of pancreatic juice flow(X) exhibited negative correlations with the changes in plasma osmolality(Y) (Y = -2.2X + 6.4, r = -0.74, p less than 0.01). Plasma osmolality and plasma vasopressin level were measured simultaneously. Plasma osmolality was elevated from 292 to 315 mOsm/kg with concurrent increase of plasma vasopressin level from 2.4 to 19.6 pg/mL. On the other hand, exogenous administration of vasopressin inhibited pancreatic juice flow and bicarbonate output dose dependently. In conclusion, elevation of plasma osmolality decreased exocrine pancreatic secretion stimulated by secretin and cerulein, and vasopressin may play an important role in its mechanism. PMID- 2230359 TI - Two subclasses of EGF receptors in the human pancreatic cancer cell lines CAPAN-1 and MIA PaCa-2. AB - The existence of different classes of EGF receptors in human pancreatic cancer cells has yet not been determined. EGF binding to two cancer cell lines (CAPAN-1 and MIA PaCa-2) was studied. Two classes of EGF binding sites were characterized. The first class of EGF binding sites demonstrated a high affinity and low capacity for EGF, with a Kd of 0.25 +/- 0.11 nM, close to the concentration of EGF suggested to be present in human pancreatic juice. The second class of EGF binding sites had a lower affinity and a higher capacity for EGF, with Kd of 1.78 +/- 0.61 nM. The total number of EGF binding sites was about 40,000/cell. Treatment of the cells with a phorbol ester, TPA, caused a complete loss of the high affinity binding sites and also caused a decrease in the concentration of the lower affinity binding sites present on the cells. Interestingly, with the increasing age of the cells, the concentration of both the high and low affinity EGF binding sites was significantly decreased. In the presence or absence of fetal calf serum, EGF, at concentrations higher than 1.10(-10)M, exerted a dose dependent mitogenic effect on the growth of the pancreatic cancer cells in culture. These data demonstrate the existence of two classes of binding sites for EGF on some human pancreatic cancer cells and a possible role of EGF in the growth of pancreatic tumors. PMID- 2230360 TI - Dissimilar trophic effects of cerulein and xenopsin on the rat pancreas. AB - Cholecystokinin (CCK), gastrin, cerulein, and other analogs are known to stimulate the growth of the rat pancreas. In the present study, we compared the trophic action of a member of this gastrin/CCK family, the amphibian peptide cerulein, with a member of the structurally unrelated neurotensin/xenopsin group, the amphibian peptide xenopsin. For this purpose, 0.56 nmols/kg cerulein, 1.0 nmols/kg xenopsin, or normal saline were injected intraperitoneally three times a day in 28 rats for 3 d. Pancreatic weight, DNA, and incorporation of 3H-thymidine into DNA were determined. In another study, pancreatic weight, DNA, and the polyamines, putrescine, spermidine, and spermine, were determined after a single dose of 2.7 nmol/kg cerulein, 4.5 nmol/kg xenopsin, or saline. The polyamines were measured by reverse-phase HPLC and post-column derivatization. Cerulein increased pancreatic weight, stimulated 3H-thymidine incorporation into DNA, and raised putrescine concentrations significantly, but led to a significant reduction of pancreatic DNA concentration. Xenopsin also stimulated 3H-thymidine incorporation into DNA, but did not affect pancreatic weight, DNA concentration, or the polyamines during the 4 h of the experiment. These findings suggest that cerulein, in the dose and intervals applied, initiated hyperplasia and induced hypertrophy of the pancreas, whereas xenopsin only initiated hyperplasia. These results, together with the dissimilar secretory effects of the two peptide families, may be the expression of a dissimilar mode of action. However, it cannot be excluded that, since cerulein is more potent than xenopsin, the differences also are owing to dosage. We conclude that cerulein and xenopsin, which both have trophic effects on the pancreas, may act by different mechanisms. PMID- 2230361 TI - Pancreatic calcifications in patients with chronic pancreatitis. A sign of long lasting or severe disease? AB - Pancreatic calcifications are particularly frequent in patients with severe pancreatic insufficiency and long-lasting chronic pancreatitis. To clarify whether calcifications point to a more severe form of the disease, irrespective of its duration, we have retrospectively analyzed patients with chronic pancreatitis submitted to the secretin-cerulein test in our center over a six year period. Out of 120 patients, calcifications were found in 55. Higher alcohol intake and longer duration of the disease were found in patients with calcifications, compared with patients without calcifications (p less than 0.001). In both groups, lipase and chymotrypsin were more severely impaired than bicarbonate; a greater reduction of pancreatic exocrine function was found in patients with calcifications, compared to those without (p less than 0.001, Mann Whitney U-test). When the patients were classified according to the duration of the disease or the severity of exocrine function impairment, higher percentages of patients with calcifications were found in the classes with more advanced disease. A log-linear analysis showed that the prevalence of calcifications was associated with pancreatic function impairment, even within the same class of duration of the disease. It is likely that calcifications mark more severe forms of chronic pancreatitis, even in the early phases of the disease. PMID- 2230362 TI - ABO blood groups and cancer of the pancreas. AB - Few investigations discussing an association between ABO blood groups and pancreatic cancer exist. We have selected a series of 224 patients with histologically-confirmed pancreatic cancer, and their ABO blood groups distribution was compared with two control groups: 7086 patients with various diseases (Group 1) and 7320 voluntary blood donors (Group 2). There was an increased number of pancreatic cancer among the patients with blood group B (relative risk 1.5 vs Group 1 p = 0.021; 1.7 vs Group 2 p = 0.0025) and a decreased number in patients with blood group O, when compared with the two control groups. PMID- 2230363 TI - Pancreatogastrostomy in experimental acute necrotizing pancreatitis. AB - Experimental acute necrotizing pancreatitis was induced retrogradely in dogs with sunflower oil injected intraductally. Then, a zipper was sutured into the abdominal wound. From the first postoperative day, three different treatments were started: first group: only conservative therapy was used; second group: removal of necrotized tissue and single peritoneal lavage were applied; and third group: the necrotic part of the pancreas was marsupialized into the stomach. Through the systematic opening of the zipper, the abdominal cavity could easily be explored and the temporal course of disease could be observed in all animals. During this regular procedure, the amylase concentration and the amount of peritoneal exudate were determined. The blood amylase and glucose levels were also measured. On the first postoperative day, the amylase level and the amount of peritoneal exudate were high in all groups. The dogs of the pancreatogastrostomized group showed a dramatic decrease of the exudate and the most advantageous temporal course of the blood amylase level. The survival rate similarly was advantageous in the pancreatogastrostomized group. PMID- 2230364 TI - Electron and light microscopy of pancreatic islets of Langerhans isolated by Trowell's T8 medium. AB - The isolation and purification of high yields of islets of Langerhans are important areas of investigation. Although it is well established that warm and cold ischemia affect islet yield and function, little information is available about the damage that occurs during the digestion period. We used Trowell's T8 medium and conventional Hank's balanced salt solution to obtain high yields of islets with morphologically-intact cells. Light and electron microscopy were used to characterize the islets isolated by the two media. Results reveal that the islets isolated by Trowells T8 medium were less fragmented and had better fine structural integrity than those isolated by the conventional medium. PMID- 2230365 TI - [Development and application of enzyme-linked immunosorbent assay using monoclonal antibody against a hemolysin (Vp-TRH) of Vibrio paraheamolyticus- evidence that Vp-TRH producing-Kanagawa phenomenon-negative V. parahaemolyticus is a human pathogen]. AB - Although it has been well established that Kanagawa phenomenon-positive Vibrio parahaemolyticus is a human enteropathogen, the Kanagawa phenomenon-negative one has been considered to be probably not pathogenic. We have found, however, an outbreak of gastroenteritis due to Kanagawa phenomenon-negative V. parahaemolyticus which produces a new toxin (Vp-TRH) resembling to Vp-TDH, a responsible toxin of Kanagawa phenomenon. In this study, we developed monoclonal antibodies against Vp-TRH which were used for development of an enzyme-linked immunosorbent assay (ELISA) for specifically detecting Vp-TRH. The ELISA was applied for analysis of production of Vp-TRH by various isolates of V. parahaemolyticus and we found that Vp-TRH-producing strains were derived mostly from human diarrheal stool, and not from the environment or sea foods. The results of the rabbit ileal loop test showed that Vp-TRH-producing (Kanagawa phenomenon-negative) strains, as well as Vp-TDH-producing (Kanagawa phenomenon positive) strains could induce fluid accumulation. These results indicate the possibility that Vp-TRH-producing Kanagawa phenomenon-negative V. parahaemolyticus is a human enteropathogen. PMID- 2230366 TI - [The epidemiological study on hepatitis B virus infection in Miyako district- relationship to the mass survey of filariasis]. AB - It has been well known that the transmission of HB virus is associated with mass inoculation and other medical procedures. In order to make clear the relation between HBV infection and the mass survey for filariasis on which sera of the examinees were drawn from their earlobes for the detecting of microfilaria with inadequately sterilized instruments, a epidemiological study was conducted in Miyako district. Okinawa prefecture, Japan, in which both HBV infection and filariasis were prevalent. A total of 2,231 inhabitants were investigated for HBV seromarkers. The over all positive rate of HBs antigen was 6.3% with the highest rate of 15.5% in the group of age 25 to 29. On the other hand, the prevalence rate of HBs antibody continued to increase along with age group, and remained to be over 60% after 30 years of age. The positive rates of both HBs antigen and antibody in the subject district were higher than those in other place of Okinawa prefecture or Japan. Comparing yearly attack rates of HBV chronologically, which were calculated from the age-specific HBV exposure rates in the district, the annual incidence of HBV infection was 6.1% (%/year) between 1954 to 1958, 5.2% (%/year) between 1959 to 1963, and then 4.4 (%/year) in the period of 1964 to 1968 in which the proportion of examinees for the survey of filariasis was the highest. In conclusion, the mass survey for filariasis was not the main factor contributing to the high prevalence of HBV infection in Miyako district. PMID- 2230367 TI - [The serotype distribution of Campylobacter jejuni strains among gastroenteritis in hospitals over 7 year period in Tokyo]. AB - Campylobacter jejuni strains isolated from gastroenteritis at 4 general hospitals of Tokyo Metropolitan during the period from 1981 to 1987 were serotype according to the slide agglutination test (TCK system) developed by the Tokyo Metropolitan Research Laboratory of Public Health. Two thousand four hundred seventy-nine strains isolated from sporadic cases among infants and children, 1,962 (78.5%) were typed by 33 typing sera numbered TCK 1 through TCK 33 and leaving 537 strains (21.5%) untypable. Out of the typable strains, 1,643 strains reacted with only single serum, while 319 strains reacted with 2 or more antisera. The most common serogroups included TCK 21, 20, 7, 1, 4, 23, 24, 10, 30 and 12. Out of the 1,250 strains isolated from sporadic cases among adults, 974 strains (77.9%) were typed and 276 strains were untypable. The most common serogroups were similar to those of infants and children. Serogroups TCK 1, 7, 4 and 21 were consistently the common serogroups every year during the 7 year study. Isolation frequency of serogroup TCK 30 have increased remarkably since 1986, while TCK 23, 14 and 9 have decreased. PMID- 2230368 TI - Biological and chemical studies on soluble protective antigen (SPA) from culture supernatant fluids of Salmonella enteritidis. AB - The chemical and biological characteristics of Soluble Protective Antigen (SPA) separated from culture fluids of Salmonella enteritidis strain 2547 were analysed. It was shown that SPA has 3-hydroxy, nonpolar fatty acids by thin-layer chromatography. The fatty acids were identified as lauric, myristic, palmitic and 3-hydroxymyristic acid using gas chromatography-mass spectrometry and mass chromatography. These fatty acids are common constituents of the lipid A obtained from S. enteritidis. SPA was found to enhance the plaque-forming cell (PFC) response to sheep erythrocytes in the recipients' spleen. In addition, SPA enhanced the clotting activity of Limulus amebocyte lysate. These results show that SPA possesses the properties of lipopolysaccharides isolated from strain 2547 by chemical procedures. PMID- 2230369 TI - [Epidemic of infectious disease with echovirus type 16--epidemic in Tono area, Gifu Prefecture in 1984]. AB - During the period from May to August, 1984, an epidemic of infectious disease with echovirus type 16 occurred in Tono area of southeast in Gifu prefecture. This virus caused children to have different clinical symptoms, one was a exanthem disease and another was aseptic meningitis. These cases confirmed by virological and serological methods were 48 cases, that is, patients with aseptic meningitis were 24 cases and patients with exanthem disease were 24 cases. By serological examination of antibody against echovirus type 16, it was confirmed that this virus type invaded Gifu Prefecture before 1984. PMID- 2230370 TI - [Epidemic of aseptic meningitis with echovirus type 18 in Gifu Prefecture in 1988]. AB - On one hundred thirty seven cases with aseptic meningitis and 36 cases except aseptic meningitis in 1988, virological and serological investigations were performed. Cases with aseptic meningitis ranged from 0 to 15 years old age, and 90.5% of them were under 8 years of age. Seven types of enteroviruses and one unidentified strain were isolated from 58 of the 137 cases (42.3%), and echovirus type 18 was recovered from 46 cases (79.3%). Echovirus type 18 was isolated also from 16 cases with acute febrile illness and exanthem etc. With the cross neutralizing test between the prototype and isolated strains in 1988 of echovirus type 18, a slight antigenic variation could be found. In the serological studies in 1989, the positive rate of neutralizing antibody to echovirus type 18, was raised remarkably in children under 8 years old. PMID- 2230371 TI - [Studies on the detection rate of Chlamydia trachomatis in married and unmarried pregnant women--field survey in Hokkaido]. AB - Chlamydia trachomatis infection in the general population has recently been attracting attention. In this regard, we examined the incidence of positive antigen in the genital organs in pregnant female women in order to investigate the prevalence of this infection. EIA (Chlamydiazyme) was performed in 5,000 married pregnant women, and in 317 unmarried women who underwent artificial termination of pregnancy. The study was carried out between June 1986 and September 1989 in Sapporo City (3,932 subjects), Kushiro City (328 subjects), Muroran City (280 subjects), Kitami City (357 subjects), Kucchan Town (220 subjects) and Urakawa Town (200 subjects). 1. Among married pregnant women, the detection rate of C. trachomatis was 6.1% (222/3,666) in Sapporo City, 7.3% (24/328) in Kushiro City, 6.1% (17/280) in Muroran City, 7.8% (24/306) in Kitami City, 6.8% (15/220) in Kucchan Town and 7.5% (15/200) in Urakawa Town, showing no particular difference according to the area. The overall detection rate was 6.3% (317/5,000). 2. The rates of detection of C. trachomatis antigen by EIA were 22.9% (61/266) and 15.7% (8/15) for the unmarried women who underwent artificial termination of pregnancy in Sapporo and Kitami, respectively. Both rates were higher than those in the married pregnant women. This result suggests the prevalence of C. trachomatis among young women showing a high level of sexual activity. 3. Among married subjects, the detection rate was 21.3% for those in their late teens, 8.9% for those in their early 20s, 6.0% for those in their late 20s, 3.7% for those in their early 30s, and 2.9% for those 35 years or older; thus, the younger they were, the detection rate became elevated. The above findings show that latent epidemics of C. trachomatis infection are present to a considerable extent among young women. PMID- 2230372 TI - [Quantitation of IgG antibodies to type Ia group B streptococcal type-specific polysaccharides measured by enzyme-linked immunosorbent assay]. AB - The type-specific polysaccharide antigen of the group B streptococcus (GBS) type Ia as extracted and purified according to the procedures of Kane and Karakawa. Using this purified polysaccharide antigen, we made a sensitive and specific assay system of enzyme-linked immunosorbent assay (ELISA) and measured the titres of of the type-specific antibodies in maternal sera and cord blood sera. The titres of antibodies in 78 pregnant women (26 Ia carriers, 18 other types of GBS carriers and 34 non carriers) were compared. A mother of an infant affected by early onset infection of GBS Ia had a titre of antibody 1:10 at delivery, while 2 years later she became a non carrier and had a titre of antibody over 1:160. The titres of antibodies in 27 pair sera of mothers and cords were well correlated. PMID- 2230373 TI - [Effects of immunoglobulin preparations on the opsonic activities against various pathogens]. AB - We evaluated the opsonic activities of human intravenous immunoglobulin (IVIG) preparations against pathogenic organisms by measuring the luminol-enhanced chemiluminescence (CL) from human polymorphonuclear leukocytes (PMN) during the phagocytosis of these organisms. Polyethylenglycol-treated IVIG significantly increased the CL of PMN by opsonization against various bacteria and Candida albicans (p less than 0.01). The high CL induced by IVIG with intact Fc-fragment showed no significant differences among lots or preparations made by different treatments. In both PMN-CL in the absence of human serum and whole blood CL at low concentration of serum complement, the CL response was not affected by pepsin treated IVIG. In the severely burned patients' blood with a very low concentration of serum immunoglobulin, IVIG with intact Fc-fragment significantly increased CL (p less than 0.01). It is suggested that administration of IVIG is useful against infections in these patients. The measurement of whole blood CL in vitro may be useful for evaluating the opsonic activity of IVIG against target pathogens in vivo. PMID- 2230374 TI - [An improved differential medium, CA medium, for differentiating Shigella]. AB - We devised a Citrate-Acetate (CA) medium for rapidly differentiating Shigella. The medium consisted of 3.0 g of sodium citrate, 2.0 g of sodium acetate, 0.2 g of glucose, 1.0 g of dipotassium phosphate, 1.0 g of mono ammonium phosphate, 0.2 g of magnesium sulfate, 5.0 g of sodium chloride, 0.08 g of brom thymol blue, 15.0 g of agar, and 1000 ml of distilled water. An evaluation was made of the CA medium, for the rapid differentiation of 23 Shigella strains, 129 Escherichia coli strains and 130 isolates, that formed colourless colonies suspected to be Shigella on SS agar plate, from feces of healthy people. The results obtained were as follows 1) On the CA medium, all Shigella strains did not grow and there was no change in colour. 2) Positive growth rates of E. coli strains after incubation for 24 hr at 37 degrees C on CA medium, sodium acetate medium (Acet) and Christensen citrate medium (C-Cit) were 96.0%, 95.2% and 28.0%, respectively. Therefore, the positive growth rate of E. coli strains after incubation for 24 hr on CA medium was significantly higher (p less than 0.01) than that on C-Cit medium. 3) Positive growth rates of isolates after incubation for 24 hr at 37 degrees C on CA medium, Acet medium and C-Cit medium were 95.4%, 83.1% and 71.5%, respectively. Therefore, the positive growth rates of isolates after incubation for 24 hr on CA medium was significantly higher (p less than 0.01) than that on Acet medium and C-Cit medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230375 TI - [A case of Pasteurella multocida infection in bronchiectasis]. AB - Pasteurella multocide (P. multocida), a small gram-negative bacillus, has been known to be the causative agent of hemorrhagic septicemia in animals. P. multocida infection in human was reported as skin abscess and/or septicemia after an animal bit or scratch. Pulmonary infections of P. multocida have been developed in the patients with chronic pulmonary diseases such as bronchiectasis. In Japan, however, P. multocida respiratory tract infections are rare. In this report, a 80-year-old female with bronchiectasis was admitted on August, 1985. She had a productive cough, hemosputum, and a low grade fever. The chest X-P on admission showed an atelectasis of the left middle lobe and severe bronchiectatic changes of the left lower lobe. P. multocida was isolated from her sputa. The chemotherapy of CTM resulted in clinical improvement. On May 1988, she complained of a productive cough and a low grade fever again. P. multocida was isolated from the sputum on several occasions in significant numbers (1 x 10(8)/ml). Recently, the cases of the chronic respiratory diseases have been increasing. We think, P. multocida is important and should be considered as a pathogen in the care of chronic pulmonary diseases. PMID- 2230376 TI - [64th symposium of the Japanese Association for Infectious Diseases. Matsuyama, 19-21 April 1990. Abstracts]. PMID- 2230377 TI - [Hemostatic changes after artificial valve replacement--especially tricuspid regurgitation]. AB - To investigate hemostatic changes after artificial valve replacement, I studied platelets, fibrinogen (Fbg), antithrombin III (AT-III), fibrinogen degradation products (FDP), thrombotest (TT), prothrombin time (PT), bleeding time (BT) and activated partial thromboplastin time (APTT) in 75 patients complicated with combined cardiac valvular disease. Twenty-nine patients with tricuspid regurgitation (TR group) and 46 patients without that (control group) were compared. 1) TR group, that contained patients with severer cases, showed a significantly longer operative time and greater bleeding volume than control group (p less than 0.01). 2) Many patients in TR group showed high serum II, frequency of abnormal platelet functions during and after extracorporeal circulation total-bilirubin and GPT level after operation and higher ICG R-value before operation than in control group. 3) After operation, the platelet count was significantly lower in TR group (p less than 0.01) than in control group, and was lowest on the 3rd postoperative day in both groups. 4) In both groups Fbg increased significantly after operation, and was lower in TR group on the 7th and 10th postoperative days than in control group. FDP was significantly higher in TR group than in control group after the 3rd postoperative day. 5) BT and APTT were similar in the two groups. 6) PT and TT were lower in TR group before operation (p less than 0.01) than in control group, and decreased after operation and administration of anticoagulants in both groups. These results indicate that patients with combined cardiac valvular disease with tricuspid regurgitation have a hemorrhagic tendency due to disorders of extrinsic coagulant, which may be caused by liver hypofunction, and are easy to bleed. PMID- 2230378 TI - [Tricuspid annuloplasty and right ventricular function in mitral valve disease]. AB - From 1985 to 1987, we examined relationship between the lesion of tricuspid valve and right ventricular function in 31 patients (male: 9, female: 22) with mitral valve disease. The median age at operation was 52 years (range 37-69 years). Group I consisted of 17 patients (MS: 10, MSR: 5, MR: 2) accompanied with tricuspid regurgitation (TR) and Group II 14 patients (MS: 12, MSR: 2) without TR. In all cases of Group I tricuspid annuloplasty (TAP) were performed correctly. De Vega methods were done in 12 cases and Carpentier rings were used in 5 cases. Cardiac catheterization was done before and after operation. And right ventricular volume was measured by right ventricular angiography. In both groups pulmonary capillary wedge pressure, pulmonary artery pressure and cardiac index were improved postoperatively. Pulmonary artery resistance (PAR) and total pulmonary resistance (TPR) in Group I were significantly higher before operation but there were no difference between two groups postoperatively. Right ventricular end-diastolic volume index (RVEDVI) and right ventricular end systolic volume index (RVESVI) in Group I were significantly improved postoperatively, but in Group II these were within normal range both pre- and postoperatively. Preoperative PAR was correlated inversely with postoperative right ventricular ejection fraction (RVEF). It means that patients with severe pulmonary vascular lesion had postoperative lower right ventricular function. In both groups, RVESVI was in inverse correlation with RVEF pre- and postoperatively. In both groups, there was an inverse correlation between the per cent change of RVESVI and that of RVEF. This means that RVESVI influenced right ventricular pump function. PMID- 2230379 TI - [Left ventricular aneurysmectomy after myocardial infarction--comparative study between true aneurysms and functional aneurysms]. AB - Postinfarction left ventricular aneurysms are pathophysiologically divided into true, functional and false aneurysm. On 14 patients treated by aneurysmectomy, we studied the difference of pre- and post-operative cardiac function between true aneurysms (9 patients) and functional aneurysms (5 patients). The aneurysm area, which is expressed as the end-diastolic perimeter (akinetic or dyskinetic area/left ventricular silhouette), was 51.6 +/- 7.7% in the true aneurysms versus 35.7 +/- 6.0% in the functional aneurysms. Preoperatively, patients with a true aneurysm had a more severe clinical status than those with a functional aneurysm (Six of nine patients with a true aneurysm were in New York Heart Association functional class III or IV). Postoperatively, all patients except one with a true aneurysm and one with a functional aneurysm improved in clinical status. Nonaneurysmal EF, that is the function of the nonaneurysmal left ventricle, has a significant correlation to postoperative LVEF (r = 0.57, p less than 0.05). Nonaneurysmal EF was 54 +/- 4% in the true aneurysm group versus 51 +/- 16% in the functional aneurysm group. LVEF improved significantly (p less than 0.05) from 31 +/- 11% preoperatively to 55 +/- 10% postoperatively in the group of true aneurysm, but did not improved significantly from 43 +/- 12% to 50 +/- 9% in the functional aneurysm group. The postoperative akinetic area was 8.1 +/- 9.1% in the true aneurysm group versus 17.8 +/- 11.5% in the functional group. We conclude that larger and more adequate resection of aneurysms improves the cardiac function in the true aneurysm group more than in the functional aneurysm group. PMID- 2230380 TI - [Comparison by 31P magnetic resonance spectroscopy of effect of simple immersion and continuous perfusion methods on organ viability of preserved rat hearts]. AB - 31P magnetic resonance spectroscopy was used to measure high energy phosphates of the heart continuously as an index of the viability of the preserved organ together with the cardiac function after preservation. Results with the simple immersion (SI) and the continuous perfusion (CP) methods were compared. With SI, ATP decreased to 14.8 +/- 4.1% of the base line after 12 hr of preservation, and phosphocreatine decreased to 27.8 +/- 6.2% after 3 hr, remaining at about 30% of the base line thereafter. With CP, ATP and phosphocreatine were unchanged even after 24 hr of preservation; they were 99.1 +/- 2.6% and 119.6 +/- 6.7%, respectively. The ATP/Pi ratio was 5.4 +/- 0.7% after 12 hr with SI and 62.2 +/- 5.8% after 24 hr with CP. LV dP/dt was 96.6 +/- 11.5% after 3 hr of SI (3-SI), which was not significantly different from the control. After 6 hr of SI (6-SI), the value was 122.7 +/- 0.2%, significantly higher (p less than 0.01) than the control. After 9 hr of SI (9-SI) or after 24 hr of CP (24-CP), it was 80.8 +/- 4.6% and 67.8 +/- 8.2%, respectively, both were significantly lower (p less than 0.01) than the control. The rate-pressure product returned to the control level after 3-SI and 6-SI, but after 9-SI or 24-CP, it was 74.2 +/- 3.7% and 53.0 +/- 11.0%, and they were significantly (p less than 0.01) lower than the control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230382 TI - [The effect of the co-existence of verapamil and residual propranolol on the left ventricular contractility]. AB - The combined effect of the residual propranolol, which was administrated up to the coronary revasculization, and verapamil, anti-supraventricular tachycardia drug, on the left ventricular contractility was evaluated with left ventricular end-systolic pressure-diameter relationship. Methods; Eighteen sheep were instrumented with ultrasonic crystals on the anterior and posterior wall, endocardium and epicardium. A pressure transducer was placed in the left ventricle. Propranolol (0.15 mg/kg) (n = 6) or verapamil (0.15 mg/kg) (n = 6) or both drugs (n = 6) were administrated intravenously, and cardiac function was evaluated. Results; In combined group, end-systolic pressure-diameter ratio (Emax) was significantly decreased (2.95 +/- 0.24 mmHg/mm) as compared to the control group (7.95 +/- 0.83), propranolol group (6.27 +/- 0.78), and verapamil group (4.54 +/- 0.77). Conclusion; Co-existence of propranolol and verapamil significantly decreased cardiac contractility. Therefore verapamil should be administrated carefully in the presence of residual propranolol, and the co existence of both drugs must be limited. PMID- 2230381 TI - [Effect of adenosine on recovery of lowered viability of preserved rat hearts measured by 31P magnetic resonance spectroscopy]. AB - The restoration of the viability of rat hearts preserved for 5 hr by 50 microM adenosine (ADN) was evaluated in terms of the cardiac function after preservation and the recovery of myocardial high energy phosphates measured by 31P magnetic resonance spectroscopy. The hearts were perfused with modified Krebs-Ringer's solution (mKRS) with ADN (ADN group) or without AND (non-ADN group) for 1 hour after 5 hr of preservation by the simple immersion method. Control hearts were perfused but not preserved. ATP and phosphocreatine had decreased to 47.2 +/- 6.6% and 28.0 +/- 8.6% of the base line by 5 hr of preservation, but the levels returned to 147.2 +/- 2.3% and 127.4 +/- 5.6% after 1 hr of perfusion with ADN; at the same time, in the non-ADN group, they were 103.8 +/- 2.3% and 115.8 +/- 8.3% respectively. The same hearts were next perfused for 3 hr with standard Krebs-Ringer's solution so as to beat after the perfusion with mKRS. After 3 hr of beating, LV dP/dt was 3330 +/- 116 mmHg/s in the ADN group, which was not significantly different from the control (3034 +/- 60 mmHg/s). However, in the non-ADN group, the value was 2516 +/- 201 mmHg/s and significantly lower (p less than 0.05) than the control. The rate-pressure product was 19350 +/- 1154 in the ADN group, not significantly different from the control (20899 +/- 709), but it was 14559 +/- 1339 in the non-ADN group, which was significantly lower (p less than 0.01) than the control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230383 TI - [Relationship between the nuclear DNA content and the prognosis in squamous cell carcinoma of the lung]. AB - Analysis of the nuclear DNA content from paraffin-embedded specimens using flow cytometry was performed on 86 patients in squamous cell carcinoma of the lung. There were no relationships between the site of tumor origin and the nuclear DNA content or the survival of the patients. The frequency of DNA aneuploidy was 74.4% among tumors, and it significantly (p less than 0.05) increased with advanced stage. The patients with DNA aneuploidy were significantly (p less than 0.01) less favorable prognosed than those with DNA diploidy. Similar results were demonstrated in patients of absolute or relative curative resections. These results indicate that DNA aneuploidy is of higher grade malignant intensity than DNA diploidy in squamous cell carcinoma of the lung. In patients with absolute or relative curative resection, DNA aneuploid tumors occurred much more often in distant metastasis. In conclusion, there were no relationships between the site of tumor origin and the biological features or the prognosis of patients in squamous carcinoma of the lung. DNA ploidy pattern is related to relapse and prognosis of the tumors. If the DNA ploidy pattern of patients on whom absolute curative resection was performed is DNA aneuploidy, adjuvant therapy should be strongly performed and carefully followed up as long as possible. PMID- 2230385 TI - [Long-term results of valve replacement in the right side of the heart in congenital heart disease--comparative study of bioprosthetic valve and mechanical valve]. AB - Valve replacements in the right side of the heart (TVR and PVR) were done on 16 patients with congenital heart disease, mainly tetralogy of Fallot and Ebstein anomaly. Including reoperations, 19 operations were performed on them and 20 artificial valves were inserted. Ten mechanical valves (7 St. Jude Medical valves, 3 Starr-Edwards valves) and 10 bioprosthetic valves (7 Carpentier-Edwards valves, 3 Ionescu-Shiley valves) were used. Age at valve replacement ranged from 9 to 52 years (mean 23.0 years), and the follow-up period was 1.28-19.8 years (mean 5.7 years). Including 2 sudden deaths, late death occurred in 4 patients, on all of whom mechanical valve replacements were done at the primary operation. Five-year survival rate of all patients was 76.4 +/- 12.1%, and 10-year survival rate was 63.6 +/- 15.4%. All the patients who received bioprosthesis at the primary operation survived at the time of this follow-up study. On the contrary, long-term results of mechanical valve was unsatisfactory with the 5-year survival of 62.5 +/- 17.1%. In spite of anti-coagulation therapy with warfarin, three patients with mechanical valve complicated thrombotic valves, which necessitated re-operations. Calcified bioprosthetic valve occurred in one patient with I-S valve 8.5 years after the implantation. Five-year complication-free rate was 87.5 +/- 11.7% for bioprosthesis, whereas it was 50.0 +/- 15.8% for mechanical valve (p less than 0.056). It is concluded that the bioprosthesis is the first choice for the valve replacement in the right side of the heart in congenital heart disease. PMID- 2230384 TI - [Surgical treatment of total anomalous pulmonary venous connection under three months of age]. AB - Nine infants under 3 months of age with total anomalous pulmonary venous connection underwent total correction between June, 1986 and September, 1988. The age at operation ranged from 4 days to 59 days, averaging 19 days, and the body weight ranged from 1,814 g to 4,105 g, with a mean of 3,050 g. The types of TAPVC were Darling Ia in 4, Ib in 1 and III in 4. All the patients were operated by the posterior approach under cardiopulmonary bypass with high flow (130-200 ml/kg/min) and mild hypothermia using modified GIK-cardioplegia, topical cooling and aortic cross clamping. Although the incision in the common pulmonary vein trunk was never extended into the pulmonary veins or vertical vein, the length of the mouth was at least 10 mm. In the postoperative management, care was taken to avoid overhydration and rapid volume infusion. Blood pressure was kept just enough to maintain urine output. Heart rate was kept over 170/min for early postoperative days with the use of isoproterenol or atrial pacing. There was no operative or late death. Postoperative course was uneventful in all cases except one with low output syndrome in which mechanical ventilation for 8 days was required. Postoperative catheterization and angiography revealed normal intracardiac pressure values and no pulmonary venous obstruction in all cases. Follow-up period ranged from 10 to 37 months, and there has been no patient with the signs of PVO. PMID- 2230386 TI - [Late results of coronary bypass grafting in patients with concomitant multifocal arteriosclerotic vascular diseases]. AB - Late results of coronary bypass graftings (CABG) in the patients with multifocal arteriosclerotic vascular diseases were reviewed. Between September 1978 and July 1989, 819 consecutive patients underwent CABG. There were 693 males and 126 females, mean ages 58 +/- 8.5 years. Of 819 consecutive patients underwent CABG, 95 patients had the coexistence of multifocal atherosclerosis (Group A). Seventy two patients had aortoiliac or femoropopliteal disease, and 29 patients had aortic aneurysm. The remaining 724 patients had no coexistence of multifocal atherosclerosis (Group B). The mean follow-up periods was 4.0 +/- 2.1 years, and the follow-up ratio was 99.4%. The 5- and 10-year survival rates were 80% and 52% in group A, and 92% and 82% in Group B, respectively. The 5- and 10-year free ratio from cardiac events were 79% and 42% in Group A, and 85% and 61% in Group B, respectively. The 5- and 10-year free ratio from noncardiac events were 53% and 38% in Group A, and 85% and 76% in Group B, respectively. The results showed that the coexistence of multifocal atherosclerotic vascular disease in patients underwent CABG significantly increase the ratio of noncardiac and cardiac events, and decreased life expectancy. PMID- 2230388 TI - [Surgical repair for pulmonary artery sling on a 46-day-old infant]. AB - Surgical repair on a 46-day-old girl with pulmonary artery sling is reported. She was suffered from dypnea and admitted to a hospital on 12 days after her birth. On chest roentgenogram atelectasis of right lung was found. She had been on respirator since 21 days after her birth. On bronchogram and pulmonary arteriogram, the trachea and right bronchus were compressed and shifted with the anomalous origin of left pulmonary artery which originated from the right pulmonary artery and passed between the trachea and esophagus. These results confirmed the diagnosis of pulmonary artery sling. Hence, she was referred to our hospital for surgical treatment. She underwent surgical repair on 46-day-old. In operation, we chose a mid-sternal splitting incision, and excised 5 mm of ductus arteriosus. Under extracorporeal circulation, the left pulmonary artery was amptated from the right pulmonary artery and pulled back to left side between the trachea and the esophagus. The left pulmonary artery was anastomosed to the main pulmonary artery at the anterior to the left bronchus. She weaned from respirator, and was extubated on the 3rd day after procedure. She recovered uneventfully in post-operative course. On the 24th day after operation she discharged from hospital. On pulmonary perfusion scanning and pulmonary arteriography performed one year after operation, the left pulmonary artery was patient with slightly decreased perfusion in the left lung. Surgical repair for pulmonary artery sling was recognized as high mortality because of frequently associated tracheobronchial anomalies. In the Japanese literature, only 4 patients survived surgically and lived in late stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230389 TI - [A case of concomitant repair of aortic regurgitation due to congenital aortic quadricuspid valve and coronary artery occlusive disease]. AB - A case of rare congenital anomaly of quadricuspid aortic valve and coexisting coronary artery occlusive disease of a 60-year-old female was presented. She was admitted to our hospital for heart murmur and angina pectoris. The echocardiography and aortography showed quadricuspid aortic valve and aortic valve regurgitation. The coronary arteriography revealed the presence of triple vessels disease. Successful aortic valve replacement and Coronary bypass grafting were performed simultaneously. PMID- 2230387 TI - [The mutual effect of ultrasound stimulation and exogenous ATP on myocardial protection during cardiac arrest]. AB - We have reported that ultrasound stimulations have a protective effect toward ischemic insult upon myocardial cells during cardioplegic arrest. However, the exact mechanism of ultrasound stimulation was not known. To elucidate this mechanism, we investigated the effect of ultrasound stimulation (UI) and/or 0.1 mMATP added to the cardioplegic solution (A) on ventricular function and adenine nucleotide changes in isolated perfused rat hearts. The hearts were perfused by working heart mode for 10 min. to determine baseline values of hemodynamic variables and they received infusion of cardioplegic solutions, followed by 20 min cardiac arrest with myocardial temperature 37 degrees C. Subsequently to the ischemic arrest, aerobic reperfusion was continued for 30 min. In group I, neither UI was irrigated nor ATP was added to cardioplegic solution. In group II and IV, ATP was added and in group III and IV, UI (1010 KHz, 0.25 W/cm2) was irrigated during cardiac arrest. Myocardial ATP was measured by Luciferase method. Myocardial ATP content after 20 min of cardiac arrest showed 12.4, 25.3, 14.5 and 32.5 (nmol/mg protein) in group I, II, III, and IV respectively, whereas it was 32.6 at the pre-ischemic cardiac arrest. The recovery of aortic output after 30 min of reperfusion revealed 30.9%, 78.9%, 79.6%, 85.4%. These data suggested the ATP depletion during cardiac arrest was attenuated by the UI and exogeneous ATP, resulted in the high recovery level of ventricular function during reperfusion. PMID- 2230390 TI - [Total cavopulmonary shunt operation for single atrium and single ventricle]. AB - A 17-year-old woman with single atrium, single ventricle, common atrioventricular valve and hemiazygous continuation underwent a total cavopulmonary shunt operation successfully. She had been cyanotic and with a heart murmur since two months of age. She was first seen at our hospital at three years of age. Catheterization, performed at the same time, had revealed pulmonary stenosis and transposition of the great arteries. At 17 years of age, catheterization was again performed, and a clinical diagnosis of single atrium, single ventricle, common atrioventricular valve and hemiazygous continuation was made. After the diagnosis was confirmed, a total cavopulmonary after ligation of the main pulmonary artery and shunt operation was performed division of the left superior vena cava, the distal end of the left superior vena cava was anastomosed to the confluent pulmonary artery. Two hours after return to ICU, extubation was done. The cardiac index was 4.36 L/min/m2 with central venous pressure of 145 mmH2O. The arterial oxygen saturation was 88.4%. After the surgery, this woman is doing well, with decreased CTR and improved exercise tolerance. Total cavopulmonary shunt can produce a marked improvement in the condition of patients with some type of complex cyanotic congenital heart disease. PMID- 2230391 TI - [Aortic valve replacement following percutaneous transluminal balloon valvuloplasty--a case report]. AB - A 71-year-old female was operated on, because of massive aortic regurgitation following elective percutaneous transluminal balloon aortic valvuloplasty (PTAV) for calcified bicuspid aortic stenosis. The damaged aortic valve was successfully replaced with a 19 mm St. Jude Medical prosthetic valve. More careful consideration may be required in selection of the candidates of PTAV, as the procedure is not so satisfactory as reported in literatures concerning its efficacy and safety. PMID- 2230393 TI - [A case of thyroid carcinoma required the incision of the thyroid cartilage for inserting the silicone T tube after extensive tracheal resection and reconstruction]. AB - A 57-year-old female with thyroid carcinoma, who had developed tracheal stenosis, underwent extensive tracheal resection and reconstruction. After the tracheal sleeve resection 5.2 cm in length, primary tracheal reconstruction was performed. Although complication did not occur at the anastomotic site, the patient had dyspnea due to cord dysfunction by bilateral recurrent nerve paralysis. After 20 days transnasal intubation we reoperated to perform a tracheostomy under neck incision. But the reconstructed trachea was too short to pull out from the mediastinum. In order to insert the silicone T tube, the incision of thyroid cartilage must be done and vocal cords were injured. The patient inserting the T tube through the laryngeal stoma had no dyspnea and no aspiration about two years after the operation in spite of palliative operation. It seemed likely that the trouble that tracheostomy could not be done would occur in some patients who had undergone extensive tracheal resection and reconstruction. But the insertion of silicone T tube through the laryngeal stoma provided a satisfactory result for airway problem. PMID- 2230392 TI - [A case of surgically treated newborn with congenital tracheal stenosis]. AB - This is a case report of a newborn with congenital tracheal stenosis which was fortunately healed by surgery. A 2,650 g female infant was born at 39 wk gestation. She began having respiratory difficulty soon after birth. Prompt endotracheal intubation was attempted, but failed. She was transferred to our hospital under assisted ventilation. Chest roentgenogram and bronchoscopy demonstrated segmental narrowing of the trachea about 2 cm distal from the vocal cord. A surgical operation was performed because respiratory management would not be enough to save the infant. Through a transverse collar incision and an upper median sternotomy, a stenotic 7 mm length of the trachea was resected and anastomosed with 5-0 Dexon suture. Postoperative course was uneventful. Histologically, the stenotic segment consisted of hypoplasia of the tracheal cartilage and fibrosis of the membranous portion. Squamous metaplasia was also recognized. There was no other report of tracheal stenosis successfully operated during the period of newborn. PMID- 2230394 TI - [An aorto-coronary bypass graft operation of left coronary ostial stenosis due to aortitis syndrome]. AB - A 24-year-old female with unstable angina due to aortitis syndrome was reported. The coronary-arteriogram in hospital showed 75 percent stenosis of the left coronary ostium. Following two months' steroid therapy for active inflammation, aortocoronary bypass graft was implanted. After the operation. This patient became free from angina attack. Steroid therapy was continued postoperatively as well. The coronary-arteriogram taken seven months after the operation, revealed the patency of the graft. PMID- 2230395 TI - [A case of giant bullae of the lung with thrombosis in the inferior vena cava and the pulmonary artery]. AB - A case of giant bullae of the lung is rarely accompanied with thrombosis in the inferior vena cava and the pulmonary artery, and because of the risk of pulmonary infarction, this case needed a surgical treatment. At this time, we removed the thrombus from the IVC as the first step of the operation, and two months later a bullectomy and the exploratory incision of the right main pulmonary artery were attempted as the second step of the operation. However, the thrombus in the pulmonary artery had spontaneously disappeared. The postoperative course was uneventful and there has been no evidence of recurrence with anticoagulant therapy. PMID- 2230396 TI - [Pleuropneumonectomy with thymectomy for invasive thymoma with pleural disseminations--a case report]. AB - A case of invasive thymoma with pleural disseminations, treated with pleuropneumonectomy and thymectomy , is presented. A 30-year-old woman was admitted with abnormal shadows in left lung field and mediastinum. On chest CT examination, the tumor shadows were located anterior mediastinum and left chest wall. Thymoma with pleural disseminations was the most likely consideration by the needle biopsy specimen of the tumor under left chest wall. Preoperative radiotherapy for anterior mediastinum mass was effective. Pleuropneumonectomy and thymectomy combined with partial resections of intercostal muscles and diaphragm were performed. Histologically, the tumor was arranged in lobular structure, composed of epithelial cells, with poorly infiltration of lymphocytes, and invaded into intercostal muscles or lung. Postoperative radiotherapy for mediastinum and left chest wall was added. Tumors may be removed completely by pan-pleuropneumonectomy and thymectomy for invasive thymoma with pleural disseminations. PMID- 2230398 TI - [A case of intralobar pulmonary sequestration associated with abnormal connection between the aberrant artery and the pulmonary artery]. AB - The patient was a 5-year-old girl and had a history of recurrent pneumonia. Angiogram demonstrated that the aberrant arteries arising from descending aorta communicated with left pulmonary A10 where the multi-lobulated cystic lesion was seen by chest X-P. The right heart catheterization revealed the step-up of oxygen saturation in distal part of left pulmonary artery A10. Diagnosis was the intralobar pulmonary sequestration with the aberrant arteries communicating with pulmonary artery. The connection between aberrant arteries and pulmonary artery in this case might be caused by the chronic inflammation in the sequestrated lung. We found 4 case reports in which the communication between aberrant arteries and pulmonary artery was evident. PMID- 2230397 TI - [An experience with simultaneous carotid endarterectomy and myocardial revascularization in a patient with calcified ascending aorta]. AB - We reported a 65-year-old male with the history of both cerebral and myocardial infarctions. Simultaneous carotid endarterectomy and myocardial revascularization (coronary artery bypass grafting = CABG) were performed. Ascending aorta was severely calcified. CABG was performed without aortic cross clamp under systemic moderate hypothermia and elective ventricular fibrillation. The wean off from extracorporeal circulation was successful. The postoperative course was uneventful. We recommend the simultaneous revascularization for the carotid and coronary artery obstructive diseases. CABG under ventricular fibrillation without aortic cross clamp was useful and unhazardous in patients presenting calcified ascending aorta. PMID- 2230400 TI - [Mitral valve replacement in 12-month-old infant with parachute mitral valve associated with ventricular and coronary sinus septal defect]. AB - A 12-month-old infant, weighting 6.7 kg, underwent mitral valve replacement with a 17 mm Bjork-Shiley prosthetic valve for parachute mitral valve, and patch closure of the associated ventricular and coronary sinus septal defects. Progressive pulmonary artery hypertension and heart failure required surgical intervention. The diagnosis of parachute mitral valve and associated lesions was established by echocardiogram and angiogram. Postoperative recovery was uneventful and he is doing well 3 years after the operation. To our knowledge this is the first successful case to be reported in the literature with such combination of the congenital anomalies. PMID- 2230399 TI - [A case of tricuspid atresia with unroofed coronary sinus]. AB - Tricuspid atresia with unroofed coronary sinus is an extremely rare cardiac anomaly. A 15-year-old boy who was successfully operated was suspected this disease preoperatively. We speculated this disease by right atrial angiography and underwent the direct suture closure of a coronary sinus defect and Fontan's operation. When we perform Fontan's operation on tricuspid atresia, we should take the existence of unroofed coronary sinus into our consideration. The echocardiography, cardiac catheterization and angiography, especially, right atrial angiography had to be carried out preoperatively. During the operation, it is important to check over the influence of cardioplegic solution from the ostium of coronary sinus. If not, elaborate inspection have to be done on the back wall of the left atrium through ASD to search for abnormal communication directly or by inserting sound from coronary sinus. PMID- 2230402 TI - AIDS: the epidemiological significance of two different mean rates of partner change. PMID- 2230401 TI - An epidemic model with a density-dependent death rate. AB - This paper deals with a mathematical model for a disease where the death rate depends on the number of people in the population. This sort of model would be suitable for diseases in developing countries or for diseases amongst animal and insect populations. We also assume that the population under consideration is regulated by the disease so that there is a mortality induced by the disease. We use a compartmental model and perform an equilibrium and stability analysis to find that there is a threshold condition. If the threshold is exceeded, then there is a unique equilibrium with disease present which is locally stable to small perturbations. We conclude by looking at several specific models and seeing how the results relate to previous work. PMID- 2230403 TI - T cell regulation in autoimmune arthritis: possibilities for immunological intervention. PMID- 2230404 TI - Interactions between immunogenic peptides and HLA-DR molecules. PMID- 2230405 TI - [MHC class I antigen expression by molar trophoblast]. AB - It is an issue for debate why molar tissues are not rejected by an immunologically potent host, since all genes in complete moles and 2/3 genes in partial moles are considered to be paternally derived. Molar trophoblasts are in direct contact with host cells, and therefore HLA expression by these cells may hold the key to the elucidation of the immunological reaction between molar tissues and the host. It has been reported that villous trophoblasts are negative and extravillous trophoblasts are positive for HLA-A, B,C, but the expressed HLA A,B,C molecule has been noted to lack their polymorphic determinants. We analyzed the reactivity of two monoclonal antibodies to a monomorphic determinant of HLA A,B,C (W6/32 and Cappel anti-HLA-A,B,C) with molar trophoblasts, using three uteri containing complete moles and two containing partial moles. The reactivity was examined by an indirect immunoperoxidase method. The staining patterns were almost identical in complete moles and partial moles. Villous trophoblasts showed a negative reaction with both antibodies. On the other hand, extravillous trophoblasts exhibited intense staining for W6/32 and negative staining for Cappel anti-HLA-A,B,C, which may suggest that the expression of a constant region as well as a variant region of HLA-A,B,C molecule is incomplete. PMID- 2230406 TI - [Influence of peritoneal fluid with endometriosis on the development of mouse embryos]. AB - To clarify the mechanism of infertility associated with endometriosis (EM), the effect of peritoneal fluid (PF) on early embryogenesis was examined. The addition of PF (5%) had no effect on the development of mouse 2-cell embryos. Since the PF is supposed to enter the oviductal cavity, PF may influence reproductive processes by modulating the intraoviductal microenvironment. As expected, PF with EM inhibited the development of 2-cell embryos co-cultured with oviducts whereas PF without EM had no effect. An increase in interleukin 1 (IL-1) has been identified in PF with EM. As with PF with EM, IL-1 inhibited the development of 2 cell embryos inasmuch as the oviducts were co-cultured. Indomethacin, an inhibitor of prostaglandin (PG) synthesis, effectively abolished the inhibitory action of both PF with EM and IL-1 on embryonic development. Moreover, PGE2 directly inhibited embryonic development. PGE2 was shown to inhibit the synthesis of protein by early embryos. These results demonstrate that PF with EM inhibits the development of early mouse embryos by acting on the oviducts. From these results it seems that an increase in IL-1 may be a causative factor in the embryo toxic properties of PF with EM. We further suggest that PGE2 secreted from the oviducts by stimulation with PF with EM, may be an ultimate contributing factor in embryo-toxicity by inhibiting protein synthesis by early embryos. PMID- 2230407 TI - [Studies of structural changes in toxemic placentae]. AB - To determine the pathogenesis and the pathophysiology of toxemia of pregnancy, we investigated ultrastructural changes in placentae. 1. Lumina of villous capillaries dilate in mild toxemia and narrow in severe toxemia as in premature delivery. Trophoblasts increase with the progress of toxemia. 2. Changes in capillaries and trophoblasts appear as a compensatory reaction at some parts of placenta and at others as dysfunction. 3. Villi of the toxemic placenta have few ramifications, and are similar to those of early gestation, but there are very few stromata. This is thought to be a maldevelopment of villi. 4. Ultrastructural changes are as follows; a) Luminal dilatation and/or narrowing of villous capillaries. b) Endothelial thickening of villous capillaries. c) Decrease in the number of slit-like capillaries. d) Increase in intermediate filaments. e) Endothelial projections like villi and vesicle in the lumen of the capillary. f) Enlargement of microvilli. g) Increase in the number of syncytial knots and cytotrophoblasts. h) Increase in the number of wrinkles on the villous surface. PMID- 2230408 TI - [Clinical significance of measurement of plasma melatonin concentration in women with irregular menstrual cycles]. AB - To study the effects of melatonin on the human hypophyseal ovarian axis, we measured the concentrations of melatonin in the plasma of women with a regular menstrual cycle and of women with an abnormal menstrual cycle, at days 5 through 10 after the onset of menstruation or withdrawal bleeding. In seven women with a regular menstrual cycle, there was a tendency for the plasma melatonin concentration to gradually decrease chronologically from 49.0 +/- 9.8pg/ml (M +/- S.E.) at 9:30 h to 19.0 +/- 4.0pg/ml at 12:00 h. On the other hand, the plasma melatonin concentration at 21:30 h was 50.3 +/- 7.4pg/ml which was almost the same as the level at 9:30 h, while the concentration during the night significantly increased chronologically to 106.3 +/- 28.6pg/ml at 24:00 h. By comparing the plasma melatonin concentration measured during the day with that measured during the night, a significant difference was discovered after 21:40 h (p less than 0.05). The plasma melatonin concentration at 10:00 h and 22:00 h in 20 women with a regular menstrual cycle was 28.1 +/- 3.4pg/ml and 72.2 +/- 9.9pg/ml, respectively, showing a diurnal rhythm with a significantly higher level during the night than during the day. On the other hand, the plasma melatonin concentration in most of the women with an anovulatory cycle or amenorrhea was within the range of the mean level of +/- 1.5 x the standard deviation obtained from the 20 women with a regular menstrual cycle. However, an increase in plasma melatonin during the night was not found in three of nine women with an anovulatory cycle and one of two women with second grade amenorrhea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230409 TI - [Ultrasonographic evaluation of advancement of uterine endometrial carcinoma; comparison with postoperative histological findings]. AB - Preoperative ultrasonographic examinations of endometrial carcinoma have been performed in 47 patients in Tokushima University Hospital since 1976. The size of intrauterine echo masses, cervical involvement and thickness of uninvolved myometrium were measured by longitudinal and transverse scan. The results were compared with postoperative histological findings. The results were as follows; 1) Endometrial echoes were identified in 94% (44/47). Echogenic masses which were characteristic of endometrial carcinoma were observed in 79% (37/47). 2) The average size of echogenic masses in pT1 carcinoma was significantly smaller than in more advanced cancers (pT2 or more). Especially when the area (longitudinal x anteroposterior diameter) of a mass was under 500 mm2 and the volume (longitudinal x anteroposterior x transverse diameter) was under 10,000 mm3, the probability of pT1 carcinoma was significantly high. 3) Eighty-seven percent (13/15) of cases with and 81% (22/27) of cases without cervical involvement of endometrial carcinoma were correctly diagnosed by ultrasonography. 4) Extrauterine extension of the tumor was found in 63% (5/8) when the thickness of the uninvolved myometrium measured by ultrasonography was under 3mm, whereas when the thickness was over 3mm, extrauterine extension of the tumor was found in only 19% (5/27). From these data, ultrasonography was effective for the evaluation of the advancement of endometrial carcinoma, especially cervical involvement, myometrial invasion and extrauterine extension. PMID- 2230410 TI - [A case of fetal conjoined twins diagnosed prenatally by ultrasound]. PMID- 2230411 TI - [Osteoporosis in postmenopausal women]. PMID- 2230412 TI - [The role of insulin in reproductive endocrinology and perinatal medicine]. AB - Soskin, in his 1946 textbook, stated that insulin may be regarded as the dominant instrument in the symphony of endocrine action that results in normal carbohydrate metabolism. After almost half a century, great progress in the medical field has revealed that insulin plays more than even he described. Some aspects of important actions of insulin in our field as investigated in our laboratory are summarized below. 1. Role of insulin in reproductive endocrinology. (1) Correlation of insulin and testosterone in normal young women and patients with polycystic ovary syndrome (PCO). The sum of serum insulin values during 75g OGTT and serum testosterone values were positively correlated in normal women and patients with PCO. Glucose transport activities in isolated adipocytes from a typical PCO patient were decreased, but insulin binding activities were not, which indicates that insulin resistance in this patients is due to some post-receptor defects. (2) Insulin may be a risk factor of endometrial carcinoma. It is well-recognized that several diseases associate with hyperinsulinemia, such as obesity, PCO, diabetes mellitus, and hypertension are risk factors for endometrial carcinoma. The sum of the insulin values during OGTT was significantly higher in patients with endometrial carcinoma than in those without. 2. Role of insulin in perinatal medicine. (1) Increase in insulin secretion during pregnancy. High serum insulin concentration during OGTT, increased secretion of urinary C-peptide, and enhanced staining of insulin in B cells by the PAP method suggest that insulin secretion is enhanced during pregnancy. (2) Insulin resistance during pregnancy. Glucose utilization rate in both pregnant and progesterone-treated rats, as assessed by a glucose clamp technique, is significantly decreased as compared to nonpregnant rats. The technique of 2-deoxyglucose injection revealed that whole body insulin resistance is due to insulin resistance in individual insulin-sensitive tissues. The activities of 3-0-methyl-D-glucose transport in isolated rat skeletal muscle and human adipocytes were found to decrease during late pregnancy, but insulin binding activities were not. These results suggest that insulin resistance during pregnancy is due to some post-receptor mechanisms. (3) Physiological meaning of insulin in fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230413 TI - [Pregnancy complicated with autoimmune diseases]. AB - Autoimmune disorders such as SLE and ITP occur more commonly in young women and are the most common complications in pregnancy. There is considerable controversy concerning the risk to the mother and fetus, and the optimal prepartum management for minimizing that risk. 1. SLE is an autoimmune disorder in which IgG antibodies such as anti dsDNA-IgG, anticardiolipin IgG, and anti SS-A/Ro IgG are produced. Lupus nephropathy accompanied by diminished serum complement (CH50) and a rise in antibodies against dsDNA is a frequent clinical problem during pregnancy, which represents the adverse effect of hypertension or superimposed toxemia and causes fetal death or intrauterine fetal growth retardation. Habitual abortion or fetal death is common in a case with high anticardiolipin IgG titre. Anti SS-A antibodies are often found in the infants of antibody-positive mothers, and the deposition of antibodies in the perinodal region cause congenital heart block. IgG or immune complexes crossing the placenta directly injures the cardiac conduction system. In these cases which have high titre crossing the placenta directly injuries the cardiac conduction system. In these cases which have high titre of autoimmune antibodies, corticosteroid therapy should be started. 2. Management of ITP in pregnancy involves the consideration of three issues: 1) treatment of maternal thrombocytopenia, 2) prediction of fetal thrombocytopenia, 3) obstetrical management. ITP increases the risk for postpartum bleeding of sufficient severity to require blood transfusion. In most of these cases, maternal platelet counts are found to be less than 30,000/mm3. Women who have symptomatic severe steroid-unresponsive ITP may benefit from intravenous IgG(IvIgG) given as elective treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230414 TI - [Hormonal control of lactation]. AB - We studied the mechanism of normal lactation, especially the roles of prolactin (PRL) and oxytocin (OXT) in the initiation of lactation, the lactation in the women complicated with endocrinological disorders, and medical therapies for stimulation and suppression of lactation. The level of serum PRL increases as pregnancy progresses, and reaches to a peak on the day of delivery. Despite high PRL level, milk secretion does not appear during pregnancy, because the sex steroid hormones suppress binding of PRL to the receptor in the mammary gland. The initiation of milk secretion in puerperal women seems to be closely related to an increase in PRL levels induced by adequate suckling. In the mechanism of suckling-induced PRL increase, OXT from posterior pituitary seems to have an important role. Furthermore, the poor response of PRL to suckling was due to insufficient stimulation to the nipples by suckling because the size of nipples were relatively small in these mothers. The other mechanism involved in lactation is suckling-induced OXT secretion. OXT stimulates milk ejection. Anxiety or fear may inhibit the OXT release. We demonstrated that the number of pulsatile release of OXT by nursing was significantly decreased by the psychological stress induced by mental calculation. In the puerperal women with prolactinomas after surgery, the serum PRL level did not increase during pregnancy and milk secretion in puerperium was poor. In the puerperal women with diabetes mellitus, milk secretion was also poor. One of the causes may be related to the low PRL response to suckling stimuli. PRL stimulates milk yield in the mammary gland, but is not commercially available.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230415 TI - [Treatment and follow-up for ovarian cancer]. AB - Current status and problems concerning the theme of the treatment and follow-up against ovarian cancer were presented. In the early stage tumors, a newly proposed staging criteria by FIGO will help to resolve the problems. Accurate staging operation may clarify the definite criteria of 'early' cancer and allows to select out subgroup of curable patients by surgery alone. Systematic lymph adenectomy may also define how extensive the initial operation should be. Considering the situations surrounding the progressive disease, however, much remains to be resolved. Which should we take as the primary treatment, surgical or chemical cytoreduction? Since neither surgery nor chemotherapy has curative potential as a monotreatment, indeed, it is important to realize to know the best timing of sequencing or combining of these treatment modalities. To define the optimal management for patients with ovarian cancer, a randomized clinical trial should be designed using various treatment protocols. PMID- 2230416 TI - [Animal models in reproductive research]. PMID- 2230417 TI - The 42nd annual scientific meeting of the Japan Society of Obstetrics and Gynecology. Tokyo, April 15-17, 1990. Abstracts. PMID- 2230418 TI - Quantitative analysis of cervical CSF and syrinx fluid pulsations. AB - The author has performed quantitative studies of cerebrospinal fluid (CSF) pulsations in the cervical region in 10 normal subjects and in 13 cases of syringomyelia using a superconducting MRI system. In the normal subjects, the caudally directed CSF flow in the anterior subarachnoid space reached its maximum velocity at 100-200 msec after the R-wave of the ECG. Measured velocities were 26 44 mm/sec at upper cervical levels and 44-124 mm/sec at lower cervical levels. Further small peaks in the caudal direction were seen at approximately 500 msec after the R-wave. Cases of syringomyelia showed lower velocities in the syrinx than in the anterior subarachnoid space, and the movements varied greatly between the cases and levels examined. CSF pulsations in the subarachnoid space were observed in all cases with Chiari malformation. These results suggest that CSF pulsations in the subarachnoid space are transmitted to the syrinx fluid, and that the movements of the syrinx fluid are influenced by various factors. PMID- 2230419 TI - [Rotational instability of the lumbar spine--a three-dimensional motion study using bi-plane X-ray analysis system]. AB - The purpose of this study is to investigate the rotational instability of the lumbar spine using bi-plane X-ray analysis system and to clarify mechanical etiology of the lumbar instability. The following results were obtained. (1) The range of rotational motion was about 2 to 3 degrees at each motion segment in the normal lumbar spine. The rotational motion was significantly large in spondylolysis, spondylolisthesis, and degenerative spondylolisthesis. (2) The rotational instability and the flexion-extension instability correlated to each other in spondylolysis and spondylolisthesis. However, in degenerative spondylolisthesis, the rotational instability and the antero-posterior instability were correlated to each other. (3) Instantaneous axis of rotation (IAR) was located at the posterior part of the intervertebral disc in the normal L4 vertebra, and more posteriorly in the L5 vertebra, while the IAR was located anteriorly in spondylolysis, and posteriorly in degenerative spondylolisthesis. (4) When the trunk was twisted, the lumbar lordotic angle was generally decreased, and the lumbar spine showed scoliotic curvature convex to the twisted direction. The apex was located at the L4/5 intervertebral level. Highly significant increases in flexion motion associated with rotation were observed at the pathological levels of spondylolysis and degenerative spondylolisthesis. PMID- 2230420 TI - [A clinicopathological study of cervical intervertebral discs--Part 1: On histopathological findings]. AB - In order to examine the aging process of the cervical intervertebral discs, a histopathological study was performed on 158 cervical discs obtained at autopsy from 37 individuals ranging in age from 3 months to 87 years. In the nucleus pulposus, degenerative changes consisting of myxomatous and slightly hyalinized degeneration were already seen in the specimens obtained from subjects in the third decade of life. Degenerative changes of the annulus fibrosus, however, tended to develop from the fourth decade of life, with myxomatous degeneration mainly in the anterior and hyalinized degeneration in the posterior annulus. The horizontal fissure of the annulus extending to its outer portion was seen more frequently in the posterior portion. In the cartilaginous plate of the vertebral body, fissure formation and degeneration became evident in the fifth decade of life. In contrast to the disc, repairing processes were observed in the cartilaginous plate. Spur formation at the corner of the vertebral body may be due to the degeneration of the outer layer of the disc leading to enchondral ossification. PMID- 2230422 TI - [Meniscus transplantation using a cryopreserved allograft--an experimental study in the rabbit]. AB - In twenty rabbits with completion of bone growth, the medial meniscus was replaced with an allograft meniscus that had been preserved at -80 degrees C for 6 to 14 days. As a control, the medial meniscus was removed and reattached without cryopreservation in 14 rabbits. Replaced menisci were examined histologically and microangiographically. Allografted menisci were found to attach to the capsule at 4 weeks. However, the attachments of the anterior and posterior horns were not stable in the majority of rabbits, because the nylon thread for anchoring was broken in these cases. There was osteophyte formation on the medial tibial plateau and the medial femoral condyle. Histological examinations revealed proliferation of vascularized synovial tissue along the meniscal surface and invasion of para-meniscal connective tissue into the meniscal substance. Chondrocytes showed regeneration in the superficial layer at 12 weeks. This study has demonstrated that cryopreserved meniscal allograft was capable of regeneration. The osteophyte formation of the medial femoral condyle and the tibial plateau appears to be produced by the abnormally unstable transplanted meniscus resulting from the insufficient anchorage of anterior and/or posterior horns. PMID- 2230421 TI - [A clinicopathological study of cervical intervertebral discs--Part 2: On morphological and roentgenologic findings]. AB - One hundred and eleven cervical vertebral bodies and 153 cervical intervertebral discs obtained in 35 autopsy cases were studied first by plain roentgenograms, discography and CT discography (CTD), and then histologically. In addition to the above studies, morphological measurements of various parts of the disc were made. Following results were obtained: 1) The anterior portion of the disc tended to become thinner with aging than the middle and posterior portions, 2) The nucleus pulposus initially located slightly anterior to the middle portion of the disc tended to move gradually to the posterior portion of the disc with aging, 3) The antero-posterior diameter of the cartilaginous plate showed a gradual decrease with aging, 4) False-negative discography+ was observed more frequently in the anterior protrusion than in the posterior protrusion, 5) The false-positive discography+ was apparently often caused by the penetration of the contrast medium into the Luschka's joint, and 6) The osteophyte of the vertebral body may be formed by enchondral ossification triggered by disc degeneration according to the histological studies. PMID- 2230423 TI - [Prolonged inflammatory reactions induced by ceramic powders in the rat air pouch model]. AB - The subcutaneous air pouch of the male Sprague-Dawley rat was used to study inflammatory potential of artificial ceramics. Local leukocyte influx, proteinase, prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) levels were measured after injection of hydroxyapatite ceramic (HAP), tricalcium phosphate ceramic (TCP) and apatite-wollastonite glass ceramic (GC) into the pouch. Synthetic monosodium urate crystals (MSU) were used as positive controls and normal saline (NS) as a negative control. The response was monitored over a period of 168 hours by irrigating the pouch with 5 ml of NS and withdrawing 4 ml. MSU produced the greatest response in leukocyte counts, proteinase and PGE2, whereas HAP, TCP and GC often appeared later than with MSU. TNF was significantly detected only after ceramics and not after MSU. The chronic and relatively prolonged reaction to HAP, TCP and GC suggests that an inflammatory reaction may occur after implantation of these ceramics in humans. The increased levels of TNF and production of PGE2, which are substances proposed to contribute to osteolysis associated with loosening, are of special interest for further research. PMID- 2230424 TI - [Experimental study on chronic entrapment neuropathy]. AB - This study was undertaken to clarify the pathology and pathophysiology of chronic entrapment neuropathy. Ten mm long Silastic tubes with internal diameter of 1.5 mm were placed on the right sciatic nerves of adult Wistar rats. Morphological and functional changes were studied from one to 14 months after tubing. The earliest changes consisted of thickening of the epineurium and perineurium, followed by breakage of nerve-blood barrier. Intraneural edema and segmental demyelination were evident at the central and peripheral areas of funiculi from 4 months after tubing. At 14 months after treatment, intraneural fibrosis was recognized. Compound action potentials and motor nerve conduction velocity were decreased in 4 and 8 month specimens respectively. Tadpole deformity of the myelin sheath was observed at 4 months and later. The fast axonal transport declined at 8 months after tubing. Our results were compatible with clinical and pathological findings of human materials. This model was thought to be useful one to elicit the pathology and pathophysiology of clinical entrapment neuropathy. PMID- 2230425 TI - [Ultrastructural studies on the articular cartilage of spontaneous osteoarthritis in C 57 black mice]. AB - In order to clarify the cause and mechanism of joint degeneration in osteoarthritis (OA), a histopathological study and ultrastructural-histochemical analysis were performed on the articular cartilage of the C57 Black mouse, a model of spontaneous osteoarthritis. Using transmission electron microscopy (TEM), in all stages of light microscopically recognized OA, we found that Golgi apparatus++ were poorly developed, intracellular microfilaments markedly increased, proteoglycan granules decreased and collagen networks broken. Observing histologically normal models of different ages by TEM, we found Golgi apparatus++ and other organelles to be well developed regardless of age. Many proteoglycan granules were seen, mainly consisting of keratan sulphate in the later months. Collagen networks were maintained. These results suggest that disturbed protein transport and sugar synthesis in chondrocytes due to the deficient development of Golgi apparatus++ caused the degenerative change in articular cartilage and that, with aging, the structure and function of the matrix were maintained mainly due to the continued presence of keratan sulphate. PMID- 2230426 TI - [Treatment of carpal injury]. PMID- 2230427 TI - [Analysis of the shear force exerted on the tibia during standing on bilateral legs with knee flexion]. AB - Biomechanical analysis of the two-dimensional models composed of roentgenographic pictures and electromyographic analysis about the shear force (Fs) exerted on tibia during standing on bilateral legs was conducted in 21 young adult males. The simultaneous contraction of the quadriceps and hamstrings was observed in all electromyograms (EMGs). Amplitude observed on EMGs of the hamstrings increased as the trunk flexion angle increased. The calculated average values of Fs were negative at every knee flexion angle; Negative value means posteriorly directed force. As the trunk flexion angle increased, posterior drawer force increased at knee flexion angles of 30 degrees and 60 degrees. The simultaneous contraction of the quadriceps and the hamstrings was considered to represent the main factor that influenced these results. The standing on bilateral legs with knee and trunk flexion was considered to be applicable in the early stages after anterior cruciate ligament reconstruction. PMID- 2230429 TI - [Effect of serum factors on skeletal growth in Perthes' disease]. AB - It is well known that patients with Perthes' disease have skeletal growth disturbances such as short stature and retardation of bone maturation. The purpose of this study was to identify serum factors which relate to the skeletal growth disturbances in Perthes' disease. The stature, bone age and the concentration of plasma somatomedin-C were measured. The stature and bone age were lower than those of normal subjects, and the concentration of plasma somatomedin-C was significantly lower than the normal value. Serum from patients with Perthes' disease was added to the culture medium of chondrocytes from rabbit articular cartilage to measure the cell number and the contents of protein and glycosaminoglycan per dish. Each of these parameters was slightly lower in the culture containing the patients' serum than that with normal serum. It may be concluded that there is some factors in the serum of patients with Perthes' disease which controls the proliferation and differentiation of chondrocytes, and somatomedin-C might be related to that factor. PMID- 2230428 TI - [An evaluation of cervical spinal canal stenosis--a correlation with cerebrospinal fluid pressure using a semiconductor and its coefficients]. AB - This study was conducted to determine whether the cerebrospinal fluid pressure (CSFP) obtained by the lumbar puncture technique is capable of evaluating the pathological state of the cervical spinal canal stenosis (CSCS). A method was developed in which the CSFP was measured with a small piezoelectric semiconductor in combination with the lumbar puncture technique. The data thus obtained were quantitatively analysed using a personal computer. Using this method, we studied patients with cervical myelopathy due to vertebral canal stenosis. The CSFP wave form obtained by compression of the cervical region was converted into a regression curve using the computer. In order to estimate the vertebral canal stenosis ratio (spinal cord/dural tube) of patients with CSCS by CSFP, multiple regression analysis was performed to obtain a multiple regression with respective parameters as expository variables. Descending curve coefficients (CND, CFD and CED) were found to be useful as parameters estimating the state of CSCS by means of CSFP analysis. On the basis of these parameters, CND, the coefficient of a descending curve obtained at the neutral cervical position, and CED, the coefficient of a descending curve obtained at the extended position, patients with CSCS were able to distinguish from normal subjects. The multiple regression equation (Y = 73.2-3890 CNA-4740 CND + 3620 CFD-10470 CEA-802 CED-0.119 NPP) was statistically significant at P = 0.01, therefore, useful in estimating the vertebral canal stenosis ratio. On the contrary, the values calculated from the multiple regression equation were not well correlated with either the JOA (Japanese Orthopedic Association) scores evaluated in accordance with the JOA Criteria or with the spinal compression ratio (anterior-to-posterior diameter/right-to-left diameter). PMID- 2230430 TI - [Effect of human interleukin-1 on cartilage metabolism]. AB - This study was undertaken to elucidate the effect of human interleukin-1 (IL-1) on the cartilage metabolism, with H235SO4 and 3H-proline as the respective indices for the metabolism of proteoglycan and collagen. We examined in vitro the 35S and 3H rates of incorporation after IL-1 was added to free chondrocytes incubated from human and porcine joint cartilage. As a result, IL-1 suppressed dose-dependently the secretion of both 35S and 3H into the supernatant of the medium containing free human or porcine chondrocytes. There was no difference between the control and the IL-1 group in the elution pattern of proteoglycan on the column-chromatogram. These results indicated that human IL-1 did not affect the molecular weight of the proteoglycan produced by human and porcine chondrocytes. PMID- 2230431 TI - [Experimental investigations of osteogenesis and chondrogenesis by implant of BMP fibrin glue mixture]. AB - The influence of fibrin glue on ectopic osteo-chondrogenesis induced by bone morphogenetic protein (BMP), which was extracted from decalcified rabbit long bones, was investigated histologically, radiographically, and electronmicroscopically. The mixtures, consisting of fibrin glue and BMP, were implanted between femoral biceps muscles of AKR mice. They were examined 3 days, 5 days, 1 week, and 2 weeks after implantation, respectively. The fibrin glue did not affect osteo-chondrogenesis by BMP under the mixture conditions, and new bone formation was seen almost in every implant. The fine network of fibrin glue seemed to be effective for adhesion, differentiation of BMP responding cells and was well cooperated on BMP. Fibrin glue network could control the area of osteo chondrogenesis by BMP. It might be due to restriction of diffusion of BMP. In addition, the whole shape of the newly formed cartilage and bone was influenced by the quantity of Aprotinin administered to fibrin glue. Fibrin glue may be regarded as an effective cooperator of BMP in the case of clinical application of BMP in the future. PMID- 2230433 TI - Experimental study of osteogenic activity of sintered hydroxyapatite--on the relationship of sintering temperature and pore size. AB - In order to determine the most appropriate properties for hydroxyapatite, four kinds of sintered hydroxyapatite (50-250 microns & 900 degrees C, 50-250 microns & 1,100 degrees C, 300-600 microns & 1,100 degrees C, and dense & 1,100 degrees C, pore size and sintering temperature, respectively) were implanted in the animals and studied histologically. In addition, the responses at different implantation sites were compared. The results are 1) hydroxyapatite sintered at 900 degrees C temperature showed higher osteogenic activity than that sintered at 1,100 degrees C in the early period. However, this difference disappeared with time, and at 26 weeks, there was no significant difference between the two groups. 2) hydroxyapatite with a 300-600 microns pore size demonstrated osteogenic activity superior to that with a 50-250 microns pore size. 3) implantation at the epiphysis produced higher osteogenic activity in the early period, compared to implantations at the metaphysis or diaphysis. This difference in bone ingrowth had disappeared at the 26-week. PMID- 2230432 TI - [Immune responses to articular cartilage reconstruction using chondrocytes allograft transplant]. AB - Epiphyseal cartilage grown in vitro was transplanted using fibrin clot into a cartilage defect produced on the femoral articular surface of the knee joints in white New Zealand rabbits 5-6 months of age. The transplantation was successful for two weeks in 64% and for 3-24 weeks in 26%. Almost dead transplanted tissues were replaced by fibrous tissues to preserve the joint function. Immunological studies such as counting of inflammatory cells in the joint fluid, evaluation of the anti-allo antibody titer by passive hemagglutination inhibition, immunofluorescence studies, and assay of cytolytic reaction by 51Cr labelled allogenic target cells suggested that the transplanted cartilage began to degenerate from two or three weeks after the transplantation partially due to humoral immunity but more importantly on account of cellular immunity. PMID- 2230434 TI - [Effect of weak direct current with silver electrodes on bacterial growth]. AB - The author studied the effect of weak direct current on bacterial growth in vitro and in vivo. In vitro, electric current was applied 20 or 100 micro A/cm2 of direct current using electrode of carbon, silver or platinum. Its inhibitory effect was observed on the growth curve of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa in the anode bath respectively. A silk thread that adsorbed Staphylococcus aureus was inserted into the intramedullary space of the tibia of Wistar rats to induce osteomyelitis. Silver electrodes were placed to apply 100 microA/cm2 of direct current for two weeks. The therapeutic effect was then evaluated in terms of X-ray findings, histological findings and changes in the viable count of Staphylococcus aureus in the intramedullary space of the tibia. It was found that application of electric current using a silver electrode was most effective for the inhibition of bacterial growth both in vivo and in vitro, and seemed to be clinically useful for treating osteomyelitis. PMID- 2230435 TI - [Prevention and treatment of complications in open leg fractures]. PMID- 2230436 TI - [Communication with the co-medical staff on orthopaedics]. PMID- 2230437 TI - [How to write a medical paper?]. PMID- 2230438 TI - [How to deal with equivocal subjects in statistical analysis of randomized controlled trials]. AB - In randomized controlled trials, it is likely that several subjects with atypical features are registered. In this paper, it was discussed from a statistical point of view how properly the subjects with the following atypical features could be dealt with; 1) subjects who were found to be not eligible for the trial after randomization, 2) subjects who did not receive the assigned regimen by the treatment protocol, 3) subjects whose outcome was ambiguous as the designated endpoint, and 4) subjects who were ambiguous whether to be regarded as censored cases. It was also emphasized that informations on equivocal subjects should be masked in the committee which is responsible for the statistical judgement. Plausible examples were added to assist the readers to understand the rules discussed here. PMID- 2230439 TI - [Immunomodulating effect of intratumoral (IT) injection of biological response modifiers (BRM) on tumor-bearing hosts]. AB - Preoperative endoscopic intratumoral injection (IT) of biological response modifiers (BRM), such as OK432, a compound composed of attenuated Streptococcus pyogens, in gastric cancer patients has been tried and this method has been improving the prognosis compared to surgical resection only. We tried to clarify this mechanism using experimental mouse system and demonstrated here the preoperative IT of OK432 significantly prolonged the survival and induced the tumor-specific cytotoxic T lymphocytes (CTL) in the spleen. By contrast, tumor necrosis factor (TNF) IT failed to prolong the survival and to induce specific CTL response, although it reduced primary tumor size significantly. To analyze why OK432 IT induce the systemic CTL response, viable tumor cells and infiltrating dish-adherent cells from the OK432 injected tumor mass were harvested and examined the class I and class II antigen expression by flow cytometer. Class I and class II antigen expression of the tumor cells remained unchanged, however, the class II positive dish-adherent cells markedly increased by OK432 pretreatment. As same in these results, histological finding in gastric cancer specimen has shown prominent increase of Langerhans cells, possessing potent antigen-presenting function and positive class II antigen, by OK432 pretreatment. Taken together, these findings strongly suggest that the increased class II positive antigen-presenting cells (APC) activity by OK432 IT augment the CTL response via cascade reaction and finally, resulted in anti-tumor efficacy in vivo. PMID- 2230440 TI - [Examination of the effects of age on prognostic factors of squamous cell carcinoma of the uterine cervix]. AB - The presence or absence of an association between age and prognostic factors of squamous cell carcinoma of the uterine cervix, including histologic cell type, depth of invasion, stromal reaction, CPL classification, and lymph node metastasis, was examined in 380 patients who had undergone radical hysterectomy. Age affected the rate of lymph node metastasis according to depth of invasion, and the metastasis rates in patients with invasion of 2/3 of the lateral side of the muscular layer (gamma type) in groups of patients in their 30s, 40s, 50s, and 60s were 40.0% (4/10), 59.3% (16/27), 36.7% (18/49), and 21.6% (8/37), respectively. Similarly, the metastasis rates in patients with invasion of the parametrium (delta type) in the above age groups were 100% (1/1), 72.7% (8/11), 46.4% (13/28), and 36.7% (11/30). Lymph node metastasis was significantly less in patients in their 60s than those in their 40s (gamma: p less than 0.01, delta: p less than 0.05). Moreover, 5-year survival rates of patients with lymph node metastasis (tested by Kaplan-Meier method) were 33.3% (N = 4), 65.0% (N = 15), 81.9% (N = 17), and 100% (N = 8) in groups of patients in their 30s, 40s, 50s, and 60s respectively, in the gamma type, and 45.0% (N = 8), 45.7% (N = 10), and 79.6% (N = 11) in groups of patients in their 40s, 50s, and 60s respectively, in the delta type. A significant difference was noted between the group of patients in their 60s and other age groups (gamma: p less than 0.01, delta: p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230441 TI - [Doppler ultrasonic assessment with hemodynamics of gynecologic tumor]. AB - Color and pulsed Doppler ultrasound examinations were done on 11 normal volunteers (NU) and 286 patients that consisted of cervical carcinoma (CC), leiomyoma and/or adenomyosis (M), endometrial carcinoma (EC), trophoblastic disease (TD), benign ovarian tumor (BO), Krukenberg tumor (KT) and ovarian carcinoma (OC). The vascularity was based on the resistance index (RI) and maximum blood flow velocity (Vmax). In uterine disease, there was significant difference (p less than 0.01) among each group, except but one correspondence between NU and CC with RI, and there was significant difference (p less than 0.001) between NU and M, CC and M with Vmax. In ovarian disease, there was significant difference among each group with RI, and there was no significant difference among each group with Vmax. Therefore, Doppler ultrasound is a useful diagnostic tool for assessing gynecologic tumor vascularity. PMID- 2230442 TI - [Mass screening for uterine cancer during the last 10 years--its present situation and problems]. AB - In Omagari city and five towns, 37,793 women were subjected to mass screening of uterine carcinoma from 1979 to 1988. The detection rate of uterine carcinoma was 0.058%. Initial screening rate was 41% 10 years ago, but in 1988, it was decreased to 18%. The peak age of the mass screening was 50-54 years old, but the carcinoma and dysplasia high degree were detected mostly in patients aged 60 years old or more. And the constitution of the age of mass screening in this study was inadequate for the screening of endometrial carcinoma. It is important to emphasize that older women (aged 60 or above) and nullipara should be encouraged to actively participate in the screening of cervical and endometrial carcinoma. PMID- 2230443 TI - [Combined radiotherapy and pre-radiation chemotherapy with cisplatin and 5 fluorouracil for advanced esophageal carcinoma. I. Clinical evaluation in cases with distant metastases]. AB - Eight patients with untreated squamous cell carcinoma of the esophagus accompanying distant metastases who were treated by one to five cycles of chemotherapy consisting of Cisplatin and 120 hour infusion of 5-Fluorouracil were reported. Two patients showed complete response (CR), four partial response (PR), one minor response, and one no response. High response rate of 75% (6 of 8) was obtained. Radiation therapy was then administered to six of the patients. After definitive treatment, CR was obtained in four, and PR in two of the cases. However, relapses were noted in all four of the CR cases, with four at distant sites, and one locally. Five of the eight patients (62.5%) survived one year and two survived three years (25%). Two patients could not receive radiotherapy because of uncontrollable lung metastases or death from duodenal ulcer. Although the follow-up period is still short, the combined treatment of radiation and pre radiation chemotherapy appears to be an effective treatment, and has made a major impact upon survival time in cases of disseminated esophageal carcinoma. PMID- 2230444 TI - [Combined radiotherapy and pre-radiation chemotherapy with cisplatin and 5 fluorouracil for advanced esophageal carcinoma. II. Clinical evaluation in cases with higher than T2 stage]. AB - Thirteen patients with previously untreated advanced squamous cell carcinoma of the esophagus were treated with pre-radiation chemotherapy followed by radiation therapy. The chemotherapy consisted of two or three cycles of Cisplatin and 120 hour continuous infusion of 5-Fluorouracil. Three patients showed complete response (CR), three partial response (PR), three minor response (MR) and four non-response (NR). The overall response rate was 46%. The predominant side effects were nausea, vomiting and anorexia. Mild or moderate degree of anemia and leukocytopenia were also noticed. However, no serious toxicity was observed. Radiation therapy was administered to eleven of the thirteen patients, excluding one patient who refused it and one patient who died during chemotherapy. In two of the eleven cases, however, radiotherapy was discontinued because of MR, and surgery was performed. In one additional case, post-radiotherapy surgery was performed. One of these three cases received curative esophagectomy. After definitive treatment, CR was obtained in 54% (7 of 13), PR in 15% (2 of 13), MR in 15% and NR in 15%. The non-effective patients (PR + MR + NR) died within nine months after the initiation of treatment. Two of the CR patients later died, one due to local recurrence and another due to aortic-esophageal fistula with no residual cancer discovered at autopsy. The remaining CR patients are still alive and well, after 11.5 to 32 months. Although the follow-up period is yet short, the combination of radiation therapy with pre-radiotherapy chemotherapy appears to be an effective treatment. PMID- 2230445 TI - [Clinical research on hyperthermia of cancer using microwave heating equipment of lens applicator type]. AB - Ninety cases with 96 tumors were treated by the 430 MHz microwave heating systems, HTS-100, at Tokyo Metropolitan Komagome Hospital, Kyoto University and Aichi Cancer Center. The results of treatment were analyzed, and the following have been clarified. Three cases are demonstrated showing feature of HTS-100. 1) The results of 383 sessions of heating by HTS-100 were analyzed, and it has been clarified that even the larger tumors, more than 5 cm both in size and depth, can be heated satisfactorily to temperatures higher than 42 degrees C. This system is capable of heating remarkably wider areas compared with the conventional microwave heating systems. 2) Hyperthermia by HTS-100 and radiotherapy were combined for treatment. The success rate (total percentage of CR plus PRa) of 89 cases analyzed was as high as 66.3%. Furthermore, local heating was successful for 60.7% of tumors, larger than 5 cm and deeper than 4 cm. 3) Combination of microwave heating and RF wave heating is a new method which is helpful for expansion of indications. 4) The frequencies of side effects of HTS-100 heating were: pain, 15.6%; sensation of heat, 6.3%; burns, 3.6%. Most of side effects were transient and slight. The higher frequency of pain than the conventional microwave heating is attributable to expansion of heating area. PMID- 2230446 TI - [Ovarian metastasis in patients with cervical cancer]. AB - The study included a total of 634 patients with cervical cancer; 311 were in stage I b and 323 were in stage II. All patients received radical hysterectomy at the Department of Obstetrics and Gynecology, Kinki University, between May 1975 and December 1986. One out of 311 patients in stage I b (0.3%) and eight out of 323 patients in stage II (2.5%) had ovarian metastases confirmed histologically. Nine patients who had ovarian metastases were investigated about stages, histological types of the cervical cancer (WHO and CPL classification), incidence of metastases in pelvic lymph nodes, corpus infiltration, parametrial infiltration, and peritoneal cytology. Results obtained were as follows: 1. As to histological types, patients with adenocarcinoma and/or PL type in CPL classification had high incidence of ovarian metastases. 2. Patients with corpus infiltration had high incidence of ovarian metastases. 3. Metastases to both ovary and pelvic lymph nodes tended to occur on the same side, but ovarian metastases and parametrial infiltration did not necessarily occur on the same side. We suggest removal of ovaries, even before menopause, in patients with cervical cancer who have cervical adenocarcinoma, or corpus infiltration, or are suspicious for metastases in more than two pelvic lymph nodes. PMID- 2230447 TI - [A combined chemo-endocrine therapy with tegafur, adriamycin, methotrexate and tamoxifen for advanced renal cell carcinoma]. AB - Six patients with advanced renal cell carcinoma was treated with a new chemo endocrine regimen consisting of Tegafur, Adriamycin, Methotrexate and Tamoxifen. Estrogen receptor was measured in four cases from renal or metastatic tumors by DCC method, presenting 14.7, 9.7, 1.0 and 0 f moles/mg protein respectively. The patients were medicated with 800-1,200 mg of Tegafur and 20 mg of Tamoxifen daily po, and 20 mg of Adriamycin and 10 mg of Methotrexate intermittently for two weeks interval iv. According to a criteria of Japan Society for Cancer Therapy, two were regarded as CR, one as PR, one as NC and two as PD. The one out of two cases with and without estrogen receptor responded favourably to this therapy. Side effects observed in the treatment were mild gastrointestinal disorders including nausea and vomiting, slight degree of leukopenia, stomatitis, pigmentation and liver dysfunction. The patients were found to be in good quality of life during the treatment because of less toxicity. This therapy can be regarded as a good modality for a treatment of advanced renal cell carcinoma. This is a first report of combined chemo-endocrine therapy with Tegafur, Adriamycin, Methotrexate and Tamoxifen for renal cell carcinoma in the world. PMID- 2230448 TI - [Studies on usefulness of postoperative adjuvant chemotherapy with lentinan in patients with gastrointestinal cancer]. AB - The usefulness of Lentinan, as an agent for postoperative adjuvant therapy, was investigated in patients with gastrointestinal cancer. Sixty-one patients were classified into three stages by a degree of advance for cancer (Stage II, III, IV). Furthermore, each group was put into the control group (C group) and the Lentinan group (L group), received 600 mg/day of Tegafur p. o. only or 600 mg/day of Tegafur p. o. and 2 mg/week of Lentinan i. v., respectively. Then total lymphocyte counts and NK cell activities were measured and analysis of lymphocyte subsets by two color flow cytometry was carried out every two months. The results were as follows: 1) Some parameters were preserved in higher levels in the L group especially in the stage IV. 2) In the stage IV, total lymphocyte counts of the L group were preserved higher levels compared to those of the C group. The same tendency was observed in OKT3, OKT4 and OKT8 positive cell counts. 3) In the stage IV, both OKT8+ x Leu15+ cell (suppressor T cell) and OKT8+ x Leu15- cell (killer T cell) counts tended to decrease in the C group. 4) In the stage IV, the NK cell activities of the L group were preserved in higher level compared to those of the C group. Leu7+ x Leu11-, Leu7+ x Leu11+ and Leu11- x Leu11+ cells counts tended to preserve in the L group. From these results, it was suggested that Lentinan had a marked immunopotentiating efficacy in the stage IV among gastrointestinal cancer patients. PMID- 2230449 TI - [A case of esophageal carcinoma with the lung and liver metastases surviving more than 3 years]. AB - A case of advanced esophageal carcinoma with liver and lung metastases who survived more than 3 years by combination chemotherapy consisting of Cisplatin and continuous 120 hours infusion of 5-Fluorouracil was reported. The primary lesion and liver metastases achieved complete response (CR) but the lung metastases attained only partial response. CR was, however, achieved by another regimen of chemotherapy. Forty months after the initiation of treatment, brain metastasis was recognized, which was controlled by radiotherapy. The patient is still alive three years after the onset of disease but with lung metastases. Quality of life in these 3 years was considered to be relatively good. PMID- 2230450 TI - [Respiratory function in respiratory failure]. PMID- 2230451 TI - [Causative diseases of respiratory failure]. PMID- 2230452 TI - [Hemodynamics of respiratory failure]. PMID- 2230453 TI - [Clinical significance of sleep and exertion in respiratory failure]. PMID- 2230454 TI - [Epidemiology and prognostic factors in respiratory failure]. PMID- 2230455 TI - [Respiratory failure and oxygen inhalation therapy]. PMID- 2230456 TI - [Treatment of acute respiratory failure]. PMID- 2230458 TI - [Multiple organ failure]. PMID- 2230457 TI - [Therapeutic management of chronic respiratory failure]. PMID- 2230459 TI - [Future aspects of home oxygen therapy of respiratory failure]. PMID- 2230460 TI - [An adult case of Alagille syndrome]. PMID- 2230461 TI - [A case of systemic lupus erythematosus complicated by primary malignant of the liver]. PMID- 2230462 TI - [A case of lupus cystitis complicated by membranous lupus nephritis]. PMID- 2230463 TI - [Important points in diagnosis of thyroid diseases]. PMID- 2230464 TI - [Essential diagnostic tests for diagnosis of thyroid diseases]. PMID- 2230465 TI - [Important points in diagnosis of thyroid functional disorders ]. PMID- 2230466 TI - [Important points in needle aspiration cytodiagnosis of thyroid diseases]. PMID- 2230467 TI - [Etiology of Basedow's disease ]. PMID- 2230468 TI - [Etiology and physiopathology of Hashimoto's disease ]. PMID- 2230469 TI - [ Therapy and physiopathology of hypothyroidism]. PMID- 2230470 TI - [Thyroid hormone resistance syndromes]. PMID- 2230471 TI - [Conservative therapy of thyroid tumors ]. PMID- 2230472 TI - [Diagnostic errors in thyroid diseases ]. PMID- 2230473 TI - [Iodine and thyroid gland function ]. PMID- 2230474 TI - [ Clinical diagnosis and therapy of thyroid diseases]. PMID- 2230475 TI - [A case of chronic myeloid leukemia with tumor formation in megakaryoblastic crisis]. PMID- 2230476 TI - [Two cases of bi-phenotypic type hybrid acute leukemia with 8;21 translocation]. PMID- 2230477 TI - [A case of chronic rheumatoid arthritis with high level of anti-DNA antibody and complement deficiency]. PMID- 2230478 TI - [Prevention of viral hepatitis]. PMID- 2230479 TI - [Differential diagnosis of acute viral hepatitis]. PMID- 2230481 TI - [Treatment of hepatitis B]. PMID- 2230480 TI - [Prediction, diagnosis and therapy of fulminant hepatitis]. PMID- 2230482 TI - [Clinical study of alcoholic hepatitis]. PMID- 2230483 TI - [A case of vitamin E deficiency polyneuropathy after gastrectomy]. PMID- 2230484 TI - [A case of non-cirrhotic portal-systemic encephalopathy treated by surgical portasystemic shunt ]. PMID- 2230486 TI - [A case of malignant lymphoma associated with diabetes insipidus]. PMID- 2230485 TI - [A case of Reifenstein syndrome]. PMID- 2230487 TI - [Progress on diagnosis and therapy of viral hepatitis]. PMID- 2230488 TI - [Clinical significance of hepatitis B virus markers ]. PMID- 2230489 TI - The management of fractures in the hand. PMID- 2230490 TI - Sub-ungual melanoma. PMID- 2230491 TI - Peripheral nerve surgery today: turning point or continuous development? PMID- 2230492 TI - Subungual melanoma of the hand. AB - Thirteen patients with subungual melanoma on the fingers had a mean delay before diagnosis of 1.2 years. Four patients presented with local recurrence after inadequate initial treatment and two presented with systemic metastases. Mean primary subungual melanoma thickness was 6.1 mm. and nine patients had Clark level IV or V disease. All patients underwent digital amputation. Two of seven patients who had localised disease initially are alive at 29 and 44 months. One of four patients who had locally recurrent melanoma is alive at 36 months. Both patients with systemic disease at presentation died. Advanced disease and delayed presentation contributed to the poor prognosis of subungual melanoma in our patients. PMID- 2230494 TI - Metacarpal fractures and the clamp-on plate. AB - Since internal fixation of metacarpal fractures has a high complication rate, most fractures should be managed conservatively, with the emphasis on early mobilisation. However, some fractures do need internal stabilisation. We propose the use of the clamp-on plate, which is simple to use, has a very low complication rate and allows immediate mobilisation. PMID- 2230493 TI - The conservative management of Bennett's fracture-dislocation: a 26-year follow up. AB - Seventeen patients who had suffered a Bennett's fracture-dislocation have been reviewed with an average follow up of 26 years. All were treated conservatively. At review, only seven patients had symptoms, but all had a decreased range of movement and grip strength. Twelve had a characteristic deformity in the hand. Radiographs showed persistent subluxation of the first carpo-metacarpal joint and marked degenerative changes. We suggest that, in the light of the poor long-term outcome, this injury should not be managed conservatively but by some operative means. PMID- 2230495 TI - Why all finger fractures should be referred to a hand surgery service: a prospective study of primary management. AB - The quality of the treatment of finger fractures by Accident and Emergency Department staff has been prospectively assessed during a six-month period. 678 finger fractures were seen in the A. & E. Department. The primary treatment of 624 of these was performed by the A. & E. staff, but in 169 of these (27%), the treatment was inappropriate. Most management errors were elementary; they included failure to prescribe antibiotics for compound fractures, failure to reduce displaced fractures accurately and unsatisfactory splintage. It is recommended that all finger fractures should be assessed and treated by surgeons with training in the management of hand injuries. PMID- 2230496 TI - The Stockport Serpentine Spring System for the treatment of displaced comminuted intra-articular phalangeal fractures. AB - A new system has been designed to treat displaced comminuted intra-articular phalangeal fractures and 20 such fracture-dislocations were treated by it. Nineteen of the patients were satisfied at an average follow-up period of 13.6 months, with a mean total active motion of 226 degrees. The results are rewarding considering the gravity of the injuries. PMID- 2230497 TI - Brachioradialis transfer for digital palsy. AB - Although brachioradialis tendon transfer is thought to offer limited tendon excursion and finger motion, we have used it to restore active thumb and digital function in eight patients. Three had Volkmann's contracture, one avulsion of forearm muscles and four had tetraplegia resulting in inability to perform activities of daily living and loss of pinch or grasp and extrinsic extension. The brachioradialis was transferred to the flexor pollicis longus, to the flexor digitorum profundus or to the common digital extensors. Except for one patient who had unremitting pain, all were pleased with their improved motion, pinch, grip, and independence. Function, however, remained abnormal in all but one. PMID- 2230498 TI - Brachioradialis forearm flap in a case of traumatic bone and skin loss at the elbow. AB - A case of traumatic skin and bone loss at the elbow is described. This was treated by a long brachioradialis flap, allowing early movements with thick and sensate cover. Anatomical studies delineate the extent of this flap. PMID- 2230500 TI - Is the treatment of enchondroma in the hand by simple curettage a rewarding method? AB - 46 enchondromata of the hand have been treated by simple curettage without bone grafting. 82% healed and 16% were left with only small bone defects. Only one patient had a clear-cut recurrence requiring re-operation. This simple method, performed on out-patient basis, is recommended. PMID- 2230499 TI - On the treatment of enchondroma. AB - We recommend simply removing an enchondroma without filling the cavity with cancellous bone or plaster-of-Paris. This method can also be applied to other benign bone conditions, such as aseptic necrosis. PMID- 2230501 TI - Properties of the fibrous structures of the wrist. AB - Every fibrous structure of ten wrists of fresh cadavers has been the object of an elastometric study. The opposite wrists have been studied surgically and then histologically with the optical microscope. Comparison between the two shows a close relationship between the mechanical features and the morphology of the bundles, which proved also to be perfectly measurable. It also displays the great differences between ligaments and tendons. Histological study of the tendons and ligaments of four other wrists subjected to manoeuvres of axial loading, rupture and bending, reinforces these statements. The therapeutic consequences are considered. PMID- 2230502 TI - The volar wrist ganglion: just a simple cyst? AB - The results of operation on 71 volar wrist ganglia are reported. The recurrence rate was 28%, occurring between 1 and 144 months (median: 5 months). The highest risk of recurrence is in a male patient, under 30 years of age, in a manual occupation, operated on by a junior surgeon. The use of a post-operative plaster slab seemed to be followed by significant wrist stiffness. 28% of the patients had evidence of damage to the palmar cutaneous branch of the median nerve. It is suggested that this could be avoided by positive identification of this nerve at operation. PMID- 2230503 TI - Volar wrist ganglia cured by carpal tunnel decompression. AB - Three patients are described, each of whom had both carpal tunnel syndrome and a volar wrist ganglion. Carpal tunnel decompression caused resolution of the ganglion. This suggests that both disorders may be caused by the same pressure phenomenon. PMID- 2230504 TI - Ice-skating injuries to the hand. AB - 166 patients with injuries due to ice-skating were seen in the local accident and emergency department over a six-month period; 60% of these involved the upper limb. 28 of the upper limb injuries were closed fractures and 24 were lacerations, almost all to the dorsum of the hand. The use of protective gloves would help to prevent these potentially avoidable injuries. "On-site" first-aid facilities help to reduce the demand on the local accident service. PMID- 2230505 TI - Morphological variations of the ulnar styloid process. AB - P.A. radiographs of both wrists were taken in 400 normal individuals to study the configuration of the styloid process of the ulna. Five different morphological variations were noticed, the commonest being an elongated process (102 wrists). Medially deviated (41 wrists), parrot beaked (27 wrists) and hypertrophic (16 wrists) patterns were less common. One person had bilateral unfused separate ossification centres for the ulnar styloid. There was no correlation between the length of the styloid process and ulnar variance. PMID- 2230506 TI - Painful hypertrophic non-union of the ulnar styloid. AB - We report the case of a 16-year-old girl suffering from painful hypertrophic non union of the ulnar styloid. She fractured the distal end of the radius four years before and had been treated conservatively. The non-union was painful and severely limited the range of movement of the wrist. Excision of the hypertrophied styloid was performed and the patient promptly resumed her activities. We believe this is the first such case reported in an adolescent. PMID- 2230508 TI - Intramuscular haemangioma of the forearm. AB - Intramuscular haemangioma, though benign, may be a serious disorder, because its large size can cause functional impairment, pain and disfigurement, which may require surgical excision. These, as well as the baffling histopathological aspects, are exemplified by this report of an intramuscular haemangioma of the forearm in an adolescent girl. Clinical recognition of a cutaneous angioma overlying a deeply-situated soft tissue tumour may aid the diagnosis of an intramuscular haemangioma. PMID- 2230507 TI - A study of age-related changes of the articular disc of the wrist in Hong Kong Chinese. AB - A cadaveric study of age-related changes in the triangular fibrocartilage of the wrist in Hong Kong Chinese confirms the high incidence of tears with increasing age. There appears to be two distinct types, linear and degenerate, with no clear evidence that the former is simply a precursor of the latter. PMID- 2230509 TI - Day surgery: an economical way to reduce waiting lists. PMID- 2230510 TI - Isolated dorsal dislocation of the scaphoid. AB - A case of isolated dorsal dislocation of the scaphoid is reported. The patient was treated surgically with a good result. PMID- 2230511 TI - Rupture of flexor pollicis longus as a complication of Colles' fracture: a case report. AB - A case of flexor pollicis longus tendon rupture as a complication of a Colles' fracture in a 17-year-old male is described. Tendon repair by means of a one stage tendon graft produced a good functional result. PMID- 2230512 TI - Fibroma of tendon sheath with bone involvement. AB - The case is reported of a 62-year-old man presenting with a fibroma of tendon sheath of the left little finger with bone involvement. This is only the third such case reported. A brief discussion of this benign soft tissue tumour follows. PMID- 2230513 TI - Angiolymphoid hyperplasia with eosinophilia in the hand: a case report. AB - Angiolymphoid hyperplasia is an uncommon condition which may give rise to difficulty in diagnosis. The case described was originally regarded as Kaposi's sarcoma, but H.I.V. testing was negative. Excision of a further lesion established the diagnosis as angiolymphoid hyperplasia. PMID- 2230514 TI - Loss of proximal phalanx of thumb following a closed injury. PMID- 2230515 TI - Surgical emphysema of the dorsum of the hand. PMID- 2230516 TI - Founders of hand surgery. Recollections of Archibald McIndoe. PMID- 2230517 TI - A modified continuous passive motion apparatus. PMID- 2230518 TI - Ligament reconstruction in tendon interposition arthroplasty of the trapezium. PMID- 2230519 TI - Flexor tendon surgery. Part I: Primary flexor tendon repair. PMID- 2230520 TI - Re: Lymphangiosarcoma of the hand. PMID- 2230521 TI - Macroglossia: a review. AB - Macroglossia is defined as a resting tongue that protrudes beyond the teeth or alveolar ridge. Complications of macroglossia include articulation errors, mandibular deformities, deglutition difficulties, and airway obstruction. Etiologies include hypothyroidism, the Beckwith-Wiedemann syndrome, lymphangiomatosis, and amyloidosis. Surgical correction of this condition at an early age may prevent or minimize the maxillofacial deformities and speech defects. PMID- 2230522 TI - A fatal case of disseminated coccidioidomycosis in Louisiana. AB - We are reporting a fatal case of coccidioidomycosis, which is an uncommon mycotic infection in Louisiana. The patient was a 21-year-old, apparently immunocompetent, pregnant black woman who had fever of unknown origin for 6 weeks. She had recently moved from Arizona. Despite her progressively worsening condition, the patient delivered a baby girl who has been doing well. An exhaustive workup and a laparotomy failed to lead to the diagnosis. The diagnosis was established by trans-bronchial biopsy a day before her death. At autopsy, disseminated coccidioidomycosis was observed. A review of the mycology records of Charity Hospital of New Orleans revealed this to be the second case of coccidioidomycosis in 20 years. Coccidioidomycosis should be considered in the differential diagnosis of fever of unknown origin in Louisianians who have lived in endemic areas, especially in pregnant patients, who are at an increased risk of disseminated infection. PMID- 2230524 TI - A case report of meningitis caused by penicillin resistant Streptococcus pneumoniae. AB - We report a case of invasive disease caused by penicillin resistant Streptococcus pneumoniae. The prevalence of penicillin and multiple drug resistant pneumococcal strains is increasing worldwide. We must assume that the incidence of clinically significant illness caused by these agents will also increase. Based on this assumption, we make suggestions as to how clinicians should alter their therapeutic approach to pneumococcal illness. PMID- 2230523 TI - The role of bacterial cultures from bronchoscopy washings in AIDS related patients. AB - The clinical significance of bronchoscopy washing cultures for bacteria had been questioned before the era of the acquired immune deficiency syndrome (AIDS), and the procedure was felt to be misleading more than helpful. Little has been mentioned of its utility in AIDS patients undergoing fiberoptic bronchoscopy. The correlation of these cultures was retrospectively reviewed for 30 bronchoscopies performed in 26 patients with advanced AIDS related illnesses. Normal respiratory flora was the most common finding in 14/28 (50%) of the cultures submitted, followed by Staphylococcus aureus in 7/28 (25%). Correlating chest radiographs with culture results revealed that in only five cases were cultures definitely or possibly relevant. All five had radiographic changes compatible with bacterial processes, and clinical findings suggestive of disease. The routine submission of bronchoscopy washings for bacterial culture in patients with HIV associated disease should be discouraged without clinical and radiologic correlation. PMID- 2230525 TI - ECG of the month. Spikes. Cardiac pacemaker rhythm. PMID- 2230526 TI - Radiology corner. Adrenal myelolipoma. PMID- 2230527 TI - Heparin, the miracle drug: a brief history of its discovery. AB - Heparin is a drug used widely in almost every field of medicine; nevertheless, very little is known about its discovery. Jay McLean, a second year medical student at Johns Hopkins University, discovered this wonderful drug in 1916 while performing research in the laboratory of W.H. Howell, MD. This is a brief account of the story told by Dr McLean before his death. PMID- 2230528 TI - Preoperative chemotherapy is beneficial for geriatric patients with locally advanced and metastatic breast cancer. AB - The relationship between aging and drug toxicity has been documented. We reviewed patients with Stage IIIB and Stage IV breast cancer with the primary tumor intact at presentation to compare the toxicity secondary to chemotherapy, the disease free survival, and the survival in both young and elderly women. Fifty-three patients were studied. All received preoperative chemotherapy and mastectomy as part of treatment for breast cancer. Sixty years was used arbitrarily to divide the patients into two groups. Data were analyzed by unpaired T-test. Hematologic, nutritional, infectious, and cardiac toxicities were noted and compared between groups. Disease-free survival was studied in patients with Stage IIIB disease. Survival was examined in patients with Stage IIIB and Stage IV disease. We could not detect any statistically significant differences between young and elderly patients in any of these groups. The elderly patients in this study seemed to derive as much benefit from chemotherapy as did younger patients. PMID- 2230529 TI - Pulmonary fibrosis as the initial manifestation of scleroderma. AB - We report a patient who developed pulmonary fibrosis before the appearance of cutaneous scleroderma. This unusual clinical presentation has been infrequently reported in the English literature. Recognition that pulmonary disease may occur before extensive skin changes in scleroderma is important to ensure proper management. PMID- 2230530 TI - The Louisiana cancer problem. Questions and answers. PMID- 2230531 TI - Atresia of the external auditory canal. AB - External auditory canal atresia (EACA) can occur bilaterally as well as unilaterally. Usually there is an accompanying auricular deformity. Surgical intervention in bilateral cases is mandatory to promote normal speech and language development. Unilateral EACA cases often do not receive surgical intervention until the patient is 18 years of age. Preoperative evaluation of the EACA patient requires behavioral audiometry, auditory brain stem evoked response, and a computerized tomographic scan. PMID- 2230532 TI - The rise of medical journalism in the United States. PMID- 2230533 TI - The immunologic paralysis of congenital infection. PMID- 2230534 TI - Building bridges in molecular rheology: the role of the microenvironment in platelet thrombogenesis. PMID- 2230535 TI - Stable isotope tracers for studies of glucose metabolism. PMID- 2230536 TI - Serum ferritin values in elite speed and synchronized swimmers and speed skaters. AB - Reports of subnormal serum ferritin values for elite athletes are widespread. Human studies evaluating performance in the ferritin-depleted state have led to a questioning of the significance of low ferritin levels for athletic performance. However, the accelerated iron metabolism and subnormal iron intake-uptake demonstrated by some athletes suggests that a point occurs in training at which the body must draw on its reserves. In consideration of this problem, serum ferritin, hemoglobin, hematocrit, serum Fe, and total iron-binding capacity levels were measured in elite Canadian female synchronized swimmers (n = 9), male speed swimmers (n = 7), and male and female speed skaters (n = 6, n = 6) over the course of two seasons of training and competition. Training sessions were monitored to document the workload carried out by each athlete. The midseason serum ferritin team values for the first and second years (mean +/- SEM) were as follows: synchro 48 +/- 10 micrograms.1 L, 24 +/- 6 micrograms.1 L; female speed skaters 57 +/- 14 micrograms.1 L, 51 +/- 7 micrograms.1 L; male speed skaters 94 +/- 27 micrograms.1 L, 72 +/- 19 micrograms.1 L; and male swimmers 66 +/- 13 micrograms.1 L, 56 +/- 7 micrograms.1 L. A significant decrease was seen in both serum ferritin and hemoglobin for the synchronized swimmers and in serum ferritin for the male speed skaters (p less than 0.05). These results suggest that a tendency exists for a decrease in serum ferritin levels from season to season.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230537 TI - Lipid peroxidation and expression of copper-zinc and manganese superoxide dismutase in lungs of premature infants with hyaline membrane disease and bronchopulmonary dysplasia. AB - The putative involvement of reactive oxygen species in the etiology of lung damage in infants receiving mechanical ventilation has been examined by comparing the levels of peroxidation and expression of the antioxidant enzymes, CuZn and Mn superoxide dismutase, in lungs from control and affected infants as well as from fetuses and infants who died postnatally after term delivery. Mean levels (+/- SD) of lung peroxidation, determined with a thiobarbituric acid method, were similar in affected and control premature neonates and in fetal subjects (1.87 +/ 1.26, 1.92 +/- 2.07, and 1.19 +/- 1.36 nmol/mg protein, respectively). Expression of CuZn and Mn superoxide dismutases was also similar in these subjects and in the patients who died postnatally. Thus activity measurements and immunoblotting studies showed continuous expression of these enzymes throughout development with no apparent change in protein levels or size. Immunohistochemical examination of lung tissue showed expression of CuZn and Mn superoxide dismutases in epithelial, smooth muscle, endothelial, and some mesenchyme components. In patients with bronchopulmonary dysplasia, alveolar walls were thickened by an excess of fibrous tissue and terminal air spaces were lined mainly by type II pneumatocytes. All structures, including abnormal fibrous components, were positive for both CuZn and Mn superoxide dismutase. Our data show that, unlike some experimental animals, expression of at least these antioxidant enzymes in human infants born prematurely is similar to that in adults, and indicate that such infants are better adapted for life in an oxygen containing environment than previously suspected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230538 TI - Glutathione, glutathione S-transferase, and transmembrane transport of glutathione conjugate in human neutrophil leukocytes. AB - Glutathione (GSH) conjugation is important in the detoxification of carcinogens and other exogenous electrophilic drugs and chemicals. The conjugation is catalyzed by GSH S-transferase. Neutrophil GSH content was 12.3 +/- 2.5 (mean +/- SD) nmol/10(7) cells, and transferase activity of cytosol preparations was 0.187 +/- 0.035 nmol/min/mg protein with 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. Maximal activity was found at a pH of 7.0 and a temperature of 40 degrees C. Apparent Km of transferase was 1.25 +/- 0.18 mmol/L CDNB, and apparent Vmax was 0.621 +/- 0.22 nmol/min/mg. GSH-CDNB conjugate was quantitated by HPLC in cells and in medium after CDNB exposure. Transport of conjugate from cells to medium increased with CDNB concentration to 50 mumol/L, and kinetic data showed two saturable transport mechanisms with apparent Km of 5.90 mumol/L and 0.265 mumol/L, respectively. Cellular GSH content fell rapidly with CDNB concentration greater than 2.5 mumol/L, and was depleted in a 10-minute incubation at a concentration of greater than 50 mumol/L CDNB. Neutrophils have a significant content of GSH and a significant amount of transferase activity, and transport of GSH conjugate involves two distinct saturable pathways. GSH depletion can be accomplished with a relatively low concentration of an exogenous chemical and could impair the ability of the cells to carry out their phagocytic functions. PMID- 2230539 TI - Conjugated catecholamines in human plasma: where are they coming from? AB - The origins of conjugated catecholamines remain poorly known. The aim of the present study was to see whether a major contribution comes from the sympathetic nervous system. We have assumed some kind of parallelism between the activity of the sympathetic nervous system, the amount of catecholamines released and taken up, and the amount of conjugated catecholamines circulating in plasma. Accordingly, an increase in sympathetic activity should be followed by an increase in the plasma level of conjugated catecholamines. The plasma levels of sulfoconjugated and glucuroconjugated catecholamines were measured in 10 patients with mental disease resistant to drug treatment, before and after electroconvulsive therapy. As expected, blood pressure, norepinephrine concentration, and epinephrine concentration in plasma were transiently increased. Neither sulfoconjugated nor glucuroconjugated catecholamines were significantly changed. Conjugated catecholamines were measured in 10 volunteers before and at the nadir of insulin-induced hypoglycemia. As expected, plasma levels of norepinephrine and epinephrine were drastically increased. Plasma levels of sulfoconjugates were decreased and glucuroconjugates increased; these were narrow but statistically significant variations. Data reported in the present article do not support a major role for the activity of the sympathetic system in fixing the level of conjugated catecholamines in human plasma. This is a negative, but nonetheless important, observation. In human subjects, currently available information suggests an important role for the intestinal wall and renal function in determining the level of circulating sulfoconjugates. PMID- 2230540 TI - Deposits of crystalline material containing silicon in surgically excised human valves. AB - Ninety-seven surgically excised natural cardiac valves were examined by scanning electron microscopy and x-ray energy spectroscopy to assess the occurrence of crystalline deposits that contain the element silicon. Valves examined included 33 mitral valves, 63 aortic valves, and 1 tricuspid valve. To reduce the possibility of surface contamination, the deep layers of some valves were examined after exposure by fracture of the valve. Crystalline material containing silicon was observed in the deep tissue. Such crystalline material was sometimes entwined within subendothelial fibers. Crystalline deposits that contained silicon were associated with 34 of 97 of these valves (35%). Among the 34 valves that showed silicon, 24 (71%) also showed microdeposits of calcific material. In view of evidence that silicon may participate in the calcification of bone, and is found in the intima of arteries, a role for this element in ectopic calcification of valves may exist. PMID- 2230541 TI - Effect of fasting on the lung glutathione redox cycle in air- and oxygen-exposed mice: beneficial effects of sugar. AB - Fasting increases susceptibility to hyperoxic lung damage in mice, at least in part, by decreasing lung glutathione level. To determine whether fasting alters other components of the glutathione redox cycle, and whether a diet of sugar alone reverses fasting's effects, normally fed, sugar-fed, and fasted mice were exposed to room air or 100% oxygen for up to 4 days. In air-exposed mice, fasting decreased glutathione peroxidase (GP) and glutathione reductase (GR) activities 15% to 20% on days 3 and 4 (p less than 0.01) and glutathione level 25% to 30% on days 2 to 4 (p less than 0.05). When corrected for protein concentration, GP and GR values were similar to those in the fed mice, but glutathione levels remained lower on days 2 and 3 (p less than 0.05). Oxidized glutathione (GSSG) was unchanged, but the ratio of GSSG to total glutathione (reduced glutathione plus GSSG) increased on day 2 (p less than 0.05). In oxygen-exposed fed mice, GP increased 62% and GR increased 39% on day 4 (p less than 0.05), the time when the lung injury was most severe; glutathione increased 30% on days 3 and 4 (p less than 0.05); and GSSG increased threefold and eightfold on days 3 and 4 (p less than 0.01). Oxygen-exposed fasted mice were all dead by day 3 (versus no deaths in the fed mice), failed to increase GR and total glutathione in response to the oxidant stress, and increased GP and GSSG on day 3 to the same extent as the fed mice did on day 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230542 TI - Serum immunoglobulins E and G anti-Aspergillus fumigatus antibody in patients with cystic fibrosis who have allergic bronchopulmonary aspergillosis. AB - Patients with cystic fibrosis frequently have pulmonary colonization with Aspergillus fumigatus (Af) and develop anti-Af immunoglobulin E (IgE) and IgG antibodies. The diagnosis of allergic bronchopulmonary aspergillosis in subjects with cystic fibrosis is difficult because of the high incidence of Af colonization, with development of humoral antibody responses. In this study, we sequentially measured serum anti-Af IgE (Af-E) and IgG (Af-G) antibodies by ELISA in subjects with cystic fibrosis. In subjects with cystic fibrosis who have allergic bronchopulmonary aspergillosis, Af-E and Af-G antibodies were significantly increased when compared with other groups of patients with cystic fibrosis who had positive skin tests or precipitins to Af (or both) (p less than 0.01, p less than 0.01, respectively). In addition, increased Af-E and Af-G levels were sometimes seen in other groups, especially subjects with cystic fibrosis who had positive Af skin tests or precipitin tests, two of whom later developed criteria diagnostic of allergic bronchopulmonary aspergillosis. Thus, serum Af-E and Af-G levels were quantitatively increased in subjects with cystic fibrosis who had allergic bronchopulmonary aspergillosis and thus adjunctive data in diagnosis. However, it also suggested that subclinical pulmonary inflammation may also occur. PMID- 2230544 TI - Clinical and experimental. Zinc metabolism in patients with the syndrome of iron deficiency anemia, hepatosplenomegaly, dwarfism, and hypogonadism. 1963. PMID- 2230543 TI - Exacerbation of acute platelet thrombus formation in stenosed dog coronary arteries with smoke from a non-tobacco-burning cigarette. AB - The tobacco industry proposes to release a "new" cigarette with a burning charcoal tip, which heats the tobacco as air is drawn through it and into the lungs of the smoker. It is claimed to be safer because the tobacco does not burn. Using our established canine model of coronary artery stenosis with moderate intimal damage, we compared this new cigarette (0.4 mg nicotine) with a regular cigarette by ventilating dogs (n = 10) with room air and then either new or regular smoke (two cigarettes over about 10 minutes). In our dog model, periodic acute platelet thrombus formation followed by embolization produced cyclical flow reductions in coronary blood flow where the rate of flow decline was proportional to the degree of in vivo platelet-vessel wall interaction. The rate of flow decline increased from -4.81 +/- 1.29 ml/min2 to -9.60 +/- 2.29 ml/min2 after ventilation with the new-type smoke (p less than 0.01). Similarly, the rate of flow decline increased from -5.43 +/- 1.28 ml/min2 to -9.28 +/- 2.31 ml/min2 after ventilation with regular cigarette smoke (p less than 0.01). Despite the lack of a clear causal link between cigarette smoking and the acute manifestations of cardiovascular disease, the data presented here indicate that the new cigarette is just as potent as regular cigarettes at increasing in vivo platelet activity and exacerbating acute platelet thrombus formation in the dog. We conclude that the new proposed non-tobacco-burning cigarette has deleterious effects similar to those of conventional cigarettes, and thus does not eliminate smoking as a risk factor in cardiovascular disease in human beings. PMID- 2230545 TI - Mosby-Year Book, Inc., through 84 years of scientific publishing. PMID- 2230546 TI - The role of functional dorsal rhizotomy for the treatment of children with spastic cerebral palsy. AB - Functional dorsal rhizotomy is now a frequently used procedure in the treatment of spastic cerebral palsy. Appropriate candidate selection is imperative for good results to be achieved. The pathophysiology of spasticity and candidate selection criteria are discussed. PMID- 2230547 TI - Outpatient left heart and coronary arteriography. The current practice at the University of Louisville School of Medicine. AB - The extension of coronary arteriography into the out-patient population provides more rapid assessment and determination of severity of coronary artery disease in a primary care and referred base population. The speed of the procedure and reduced recovery period are reflected in enhanced cost containment and improved patient compliance and satisfaction. Further technological advancement in this rapidly developing technological field continues to provide improved patient care. PMID- 2230548 TI - Current management of soft tissue sarcomas. AB - Sarcomas are rare. They comprise a heterogenous group of malignancies. Prognosis is determined by presence of distant metastasis, the size of the primary malignancy, and the grade and histogenic classification of the tumor. Careful consideration of the extirpative surgical resection is necessary for appropriate placement of the biopsy incision for diagnosis. Effective therapy includes adequate surgical resection in the form of radical compartmental resection, wide local excision with either pre- or postoperative radiotherapy, or amputation. Progress over the last two decades has resulted in limb salvage and maintenance of limb function for the vast majority of patients. PMID- 2230549 TI - Unterberger stepping test: a useful indicator of peripheral vestibular dysfunction? AB - Deviation of gait in a stepping test has been proposed as a useful indicator of peripheral labyrinthine dysfunction. A prospective study of 26 patients suspected of having uncompensated peripheral labyrinthine dysfunction and 49 normal patients with normal labyrinthine dysfunction showed no significant difference in performance of the Unterberger stepping test between patients with electronystagmographically significant canal paresis and those with normal vestibular function. PMID- 2230550 TI - Size variation of mastoid air cell system in Indian people at different age groups: a radiographic planimetric study. AB - A radiographic planimetric study of mastoid air cell system was carried out on 100 normal human subjects of which 50 were males and 50 females--who were further subdivided into five age groups. They had no history of past ear disease or any other clinical ENT abnormality. The mean area of the mastoid air cell system was measured planimetrically on X-rays and the data analysed according to age and sex. It was 12.05 +/- 0.67 cm2 in males and 11.45 +/- 0.70 cm2 in females (which are more or less the same as that of Western people). The size of the cranial bones has no apparent role in the size variation of the mastoid air cell system. The development of the latter was very rapid up to 10 years of age in both sexes and it continued even after 20 years of age but at a much slower rate. PMID- 2230551 TI - Ligmaject system for local anaesthesia in otology. AB - The Ligmaject syringe for local anaesthetic injection incorporates a pistol-grip handle and a ratchet system designed to inject a very tiny aliquot of anaesthetic per 'click'. This instrument was used to provide local anaesthesia for 22 otological procedures on consenting adults. The performance of the Ligmaject syringe compared favourably with that of the conventional dental syringe in terms of patient acceptability and user convenience. PMID- 2230552 TI - Comparison of the Goode T-tube with the Armstrong tube in children with chronic otitis media with effusion. AB - Treatment of otitis media with effusion is focused on reaeration of the middle ear cavity. In achieving long-term aeration, the insertion of ventilation tubes that have a long duration of stay can be beneficial. The results are presented of a trial in which the Goode T-tube was compared with the Armstrong tube. Fifteen children were treated between 1981 and 1986 with a T-tube in one ear and a conventional tube in the other. The results are different with regard to duration of stay in the tympanic membrane. Re-insertions were necessary in 47 per cent in the Armstrong group and in 20 per cent in the T-tube group. Otorrhoea occurred in 20 per cent of the Armstrong and 13 per cent of the T-tube intubated ears. A persistent perforation was present in 6 per cent of the ears in both groups. It is concluded that the Goode T-tube is indicated primarily in cases when long-term ventilation is needed. PMID- 2230553 TI - Delayed facial palsy following uncomplicated stapedectomy. AB - We report six cases of partial lower motor neurone facial palsy occurring between four and ten days after uncomplicated stapedectomy. The aetiology is unclear but recovery was rapid and complete in all patients. PMID- 2230554 TI - Long-term results of revision endolymphatic sac surgery. AB - The results of revision endolymphatic sac surgery on 30 patients with unilateral Meniere's disease are presented. Good control is achieved in 73.3 per cent of cases at six months, falling to 56.7 per cent at one year and only 33.3 per cent by four years. The long-term results are disappointing but are more favourable if the initial surgery was successful, if the hearing remains fluctuant and improves on glycerol dehydration prior to the revision procedure and also if the sac is intubated. The current place of endolymphatic sac surgery is discussed and revision surgery only recommended for carefully selected cases. PMID- 2230555 TI - Comparison of electro and chemical cautery in the treatment of anterior epistaxis. AB - In the ENT Department of the Royal Victoria Hospital, Belfast, the impression (supported only by anecdotes) was that electro-cautery was superior to chemical cautery in the treatment of simple anterior epistaxis. Since no evaluation of the relative merits of electro and chemical cautery has been reported, a prospective randomized study was conducted to assess the effectiveness of electro-cautery and cautery with silver nitrate. The results of the study showed that there was no statistically significant difference between the two methods in either controlling the epistaxis or in the incidence of complications. It is concluded that since cautery with a silver nitrate tipped applicator is simpler, and of equal effectiveness, it would appear to be the treatment of choice for simple anterior epistaxis. PMID- 2230556 TI - Role of endoscopy in diagnosing scleroma in its uncommon sites. AB - Eighty cases suffering from rhinoscleroma were studied. Suspected cases were examined by sinoscopy, nasopharyngoscopy and bronchoscopy for detection of secondary involvement in these sites. Antroscleroma, salpingoscleroma and tracheo bronchoscleroma have been found in a relatively high percentage of cases. The role of endoscopy in early diagnosis, initial symptomatic treatment and follow-up cases is discussed. PMID- 2230557 TI - Laryngeal growth in infancy. AB - Growth of the cricoid ring in infants is studied. In the first two weeks of life a small ring seems correlated with the fact of early infant death. Therefore we suggest that mortuary specimens at this age are not a reliable guide to the size of the cricoid in thriving infants. Rates of growth from ages of two weeks to three years are given for the specimens examined. Comparison with similar measurements carried out in England show that the specimens collected here were systematically smaller for a given age. PMID- 2230558 TI - Smoking cessation in chronic Reinke's oedema. AB - In evaluating the long term results of surgical treatment of Reinke's oedema, there has been found to be a high incidence of recurrence. The recurrence rate is significantly lower amongst those patients who gave up smoking after treatment. A group of patients with chronic Reinke's oedema were followed for six months. Maximum efforts were made to help the patients to stop smoking. Twenty-nine patients entered the study, but only eight of them (28 per cent) refrained from smoking; all were women (39-70 years) and all experienced reduced discomfort, although none of the voices were restored to normal. Diffuse laryngitis disappeared completely, but the oedema did not disappear entirely in any patient. Before treatment of chronic Reinke's oedema patients must be well advised and informed, and if surgery is decided upon, they must be urged most strongly to stop smoking, if they wish to enhance the possibility of satisfactory long-term results. PMID- 2230559 TI - Second primary tumours of the larynx following bronchial carcinoma. AB - The occurrence of multiple primary malignancies in patients with laryngeal cancer is well known. The possibility that lung cancer patients may be at risk of subsequent laryngeal cancer is less well recognized. The possibility of laryngeal cancer developing later has implications for the follow-up of lung cancer patients. Three cases of subsequent laryngeal primary cancer occurring in survivors of bronchial cancer are presented and the implications are discussed. PMID- 2230560 TI - Alternating cisplatinum and VAC ineffective in end stage squamous cell carcinoma of the head and neck. AB - Sixteen patients with end stage squamous cell carcinoma of the head and neck were admitted to a phase II study of alternating courses of cisplatinum (100 mg/m2) and VAC (vincristine 1.4 mg/m2, adriamycin 50 mg/m2, cyclophosphamide 750 mg/m2) given at three weekly intervals. Only two patients achieved a response (12 per cent). The median survival time was 62 days which is much the same as that of a similar group of patients who received no chemotherapy in a previous trial (70 days). PMID- 2230561 TI - Head and neck cancer and ageing: a retrospective study in 438 patients. AB - To evaluate whether age over 70 years represents a prognostic factor in head and neck cancer, we reviewed all cases observed between 1981 and 1984. Four hundred and thirty-eight (438) patients were considered in relation to three age groups (less than or equal to 59, 60-69, and greater than or equal to 70 years, defined as non-elderly, mid-elderly and elderly respectively). The main parameters analyzed included histological diagnosis (no difference emerged among the three age groups); anatomical site (hypopharyngeal carcinoma was most frequent in non elderly patients); TNM stage (an higher incidence of early stages was seen in the elderly); performance status (better in the non-elderly); previous illnesses (life-style related diseases were more frequent in the non-elderly); contraindications to surgery (more frequent in the elderly); surgical treatment ('en bloc' resections were more often employed in the non-elderly); post operative complications and local control (no difference between the three groups); multiple primary malignancies (head and neck, oesophagus and lung were more frequent in non-elderly patients) and survival (no difference). Although age affects several features of head and neck cancer patients, it does not appear from the present study to be an independent prognostic factor for local control and survival. With regard to survival, stage appeared to be the most important prognostic factor. PMID- 2230562 TI - Endolymphatic hydrops precipitated by haemodialysis. AB - We report a case of endolymphatic hydrops preceded by haemodialysis in the contralateral ear of a patient with known Meniere's disease, and discuss the possible mechanism. It is suggested that the sudden decrease of plasma osmolality during haemodialysis acts as a reverse glycerol test. The audiometric and electrophysiological recordings pre- and post-dialysis and the induction of the Meniere's triad of symptoms during dialysis, were strongly indicative of the presence of endolymphatic hydrops. PMID- 2230563 TI - Epistaxis as an unusual presentation of an antrochoanal polyp. AB - Antrochoanal polyps rarely present with severe epistaxis. We present the case of a young male patient who presented in such a manner, thus leading to the suspicion of an angiofibroma as the underlying pathology. The radiological investigations, treatment and pathological features are discussed. PMID- 2230564 TI - A 'silent' intracranial complication of frontal sinusitis. AB - Intracranial complications of frontal sinusitis, although rare today, do still develop despite widespread use of antibiotics. We report a case which demonstrates how silently a frontal lobe abscess may present with subtle changes in mood and behaviour, with no focal neurological signs. Diagnosis and management are discussed and a brief review of the incidence of intracranial complications of frontal sinusitis, mode of spread, clinical presentation, investigations, treatment and bacteriology is presented. PMID- 2230565 TI - Rhinosporidiosis associated with squamous cell carcinoma in the tongue. AB - The peritumoural region of a squamous cell carcinoma of the tongue when examined with light and electron microscope showed nodular bodies in the submucosa with all the distinctive features of 'sporangium and 'spores' of rhinosporidiosis. The occurrence of rhinosporidiosis in the tongue along with malignancy has not been reported hitherto. Some interesting observations and causal relationships are discussed. PMID- 2230566 TI - Infectious mononucleosis complicated by lingual tonsillitis. AB - Although upper airway obstruction and superimposed infection are well-known complications of infectious mononucleosis, lingual tonsillitis in this context has not been mentioned in the literature. We describe a case of acute bacterial lingual tonsillitis with airway obstruction complicating infectious mononucleosis. The role of the base of tongue region in the pathophysiology of infectious mononucleosis is discussed. PMID- 2230567 TI - Acute upper airway obstruction following Teflon injection of a vocal cord; the value of nebulized adrenaline and a helium/oxygen mixture in its management. AB - A 67-year-old man presented with a 45-year history of a week voice. This was result of polio which had left him with a right vocal cord palsy. The patient underwent a Teflon injection of the right vocal cord under general anaesthesia to improve the quality of his voice. In the immediate post-operative period, he suffered acute upper airway obstruction. The problem of acute upper airway obstruction following Teflon injection is considered and its management with nebulized adrenaline and a helium/oxygen mixture is discussed. PMID- 2230568 TI - Malignant adenolymphoma of the parotid gland: report of carcinomatous transformation. AB - Malignant transformation of an adenolymphoma (Warthin's tumour) is a rare event. This paper presents a case of carcinoma arising in an adenolymphoma of the parotid gland. PMID- 2230569 TI - Wegener's granulomatosis: anti-neutrophil cytoplasmic antibody hsi (ANCA) PMID- 2230570 TI - Adenocarcinoma of the para-nasal sinuses due to wood dust. PMID- 2230571 TI - Decline in the prevalence of childhood deafness in the Jewish population of Jerusalem: ethnic and genetic aspects. AB - A longitudinal study was performed on 147 Jewish children with bilaterally sensorineural hearing loss of moderately severe to profound degree, born in Jerusalem during the eighteen years 1968-85. The prevalence rate of these children declined during the years 1977-85, and at the same time the rate of consanguinity of their parents decreased; this decline was more evident in the genetic group among children with non-Ashkenazi ethnic origin. No such decline was found among the Ashkenazi children and no consanguinity among parents of these children was recorded. Our study supports the assumption that restriction of consanguineous matings may affect the prevalence of genetic deafness in children in a well-defined population. We have tried to remain unbiased and concede certain shortcomings in our present study. PMID- 2230572 TI - Dysequilibrium and otitis media with effusion: what is the association? AB - An association between non-suppurative otitis media (NSOM) and symptoms of dysequilibrium has been observed but not previously quantified in children (Gates, 1980; Busis, 1983; Blayney and Coleman, 1984). This study compared the incidence of balance related problems in 154 children with surgically proven glue ear and 51 children with normal ear function. Symptoms ranging from true vertigo to mild ataxia were discovered in 22 per cent of the children with NSOM but in none of those within the control group (p less than 0.001). Periods of dysequilibrium were associated with episodes of otalgia in 64 per cent of the children but were not increased in those with unilateral compared to those with bilateral effusions. Complete resolution of symptoms occurred in 85 per cent of children following the insertion of grommets. A history of balance disturbance should be actively sought in all children with otitis media with effusion, and when present, provides a strong indication for early operative intervention. PMID- 2230573 TI - Tympanosclerosis of the middle ear: late results of surgical treatment. AB - The late results of one stage operation for middle ear tymanosclerosis in 73 patients during the period January 1965 to December 1980 are presented. Mean observation time was 11.2 years (range 3-20.2 years), with a follow-up rate 86 per cent. Among 64 patients with stapes fixation, 59 had removal of tympanosclerotic masses and stapes mobilization, and five cases underwent stapedectomy. The series was divided into six groups and the results analyzed. The best and most stable results occurred in the group with stapes mobilization and an intact ossicular chain followed by the group with stapes mobilization and Type II tympanoplasty with incus interposition. The poorest late results were obtained in ears with lacking stapes crura and stapes mobilization, and in ears subjected to stapedectomy. No case of post-operative sensorineural hearing loss occurred. We recommend that care is taken to preserve an intact ossicular chain at stapes mobilization performed at the same stage as myringoplasty. Also in ears with a defective ossicular chain but intact stapes with tympanosclerotic fixation we recommend stapes mobilization in one stage. In ears with fixation of the stapes footplate and defective crura, we recommend stapedectomy or stapedotomy in two stages. PMID- 2230574 TI - Why paranasal sinuses? AB - This essay attempts to address the perennial question 'Why Paranasal Sinuses?'. In doing so it highlights the flaws in many much-favoured but ill-founded theories concerning the role of these sinuses in humans. It is concluded that the question can only be fully answered through a greater understanding of differential growth changes within the craniofacial massif. PMID- 2230575 TI - Mucosal thickening on sinus X-rays and its significance. AB - Mucosal thickening is commonly seen on X-rays of the paranasal sinuses taken in the ENT department. This sometimes leads to a sinus washout, which is clear, even though the X-rays were strongly suggestive of disease. This paper examines the prevalence of sinus X-ray anomalies in a general population, having facial X-rays for conditions other than possible sinus disease. The study suggests that up to 50 per cent of the so-called normal population may have sinus X-ray appearances consistent with sinus disease, and this may partly explain clear returns on sinus washout. PMID- 2230576 TI - Multiple primary malignancies in patients with malignant tumours of the nasal cavities and paranasal sinuses. AB - The incidence of multiple primary malignancies (MPM) was analysed in 1297 patients with malignant tumours of the nasal cavities and paranasal sinuses. The patients were followed for a minimum of six years or until death. The incidence of MPM was 3.4 per cent (44/1297) which is lower in patients with malignant tumours of other regions in the upper aerodigestive tract. Five of the 44 patients had second malignancies within previously irradiated areas. There was a difference between the proportion of histologies occurring in irradiated tissues compared with the overall 1297 patients. This finding suggests that radiotherapy may induce a second cancer. PMID- 2230577 TI - Radiation therapy of laryngeal cancer: a twenty year experience. AB - This paper reviews a 20 year experience of radiation treatment of 286 laryngeal cancers and presents results with a minimum five year follow-up. All cases presented had glottic or supraglottic squamous cell carcinomas with no clinical evidence of nodal metastasis. A policy of primary radiotherapy with surgery for salvage of treatment failures, produced control of primary disease and prevention of metastases superior to most other regimes documented in the literature. PMID- 2230578 TI - Effect of microwave and ionizing radiation in patients with recurrent laryngeal carcinoma. AB - This study describes the treatment and survival of 54 patients with gross recurrent laryngeal carcinoma after radiotherapy. Twenty-six patients were treated with local ultra-high frequency hyperthermia in combination with radiotherapy and chemotherapy (HRCH). Twenty-eight control patients were treated with radiotherapy and chemotherapy (RCh). Eight patients (33 per cent) in HRCh showed a three year survival but no patient in the RCh group. At two years 18 patients (75 per cent) in HRCh and two (7 per cent) in RCh survived. PMID- 2230579 TI - Another hazard of ear syringing: malignant external otitis. AB - A case of malignant external otitis is presented. This occurred in a healthy 72 year-old non-diabetic, non-immuno-compromised man after ear syringing. The infection was treated with oral ciprofloxacin for eight weeks with complete resolution. PMID- 2230580 TI - Sudden sensorineural hearing loss as a complication of non-otologic surgery. PMID- 2230581 TI - Recurrent Bell's palsy in pregnancy. AB - A case of recurrent Bell's palsy occurring in two successive pregnancies in a 37 year-old woman is presented. The causes of facial nerve paralysis of the lower motor neurone type are discussed. The rate of recurrence of Bell's palsy during pregnancy is unknown. Treatment with corticosteroids of Bell's palsy during pregnancy poses the threat of possible side effects on the fetus. PMID- 2230582 TI - Hoarseness as the sole presenting symptom of foramen magnum meningioma. AB - Foramen magnum tumours are rare. They may present with bizarre symptoms and mimic many conditions. We report a presentation with the sole complaint of hoarseness, never previously described in the literature. Voice returned to normal after surgical removal of the foramen magnum meningioma. PMID- 2230583 TI - Unusual type of foreign body in the maxillary sinus. AB - A broken end of the spear presenting as a foreign body in the nasopharynx and right maxillary sinus in a 19-year-old Papua New Guinean is described. The types of foreign bodies and their mechanisms of introduction into this site are summarized. PMID- 2230584 TI - Unusual lymphoproliferative oropharyngeal lesions in heart and heart-lung transplant recipients. AB - Three unusual cases of oropharyngeal lympho-proliferative lesions were seen in recipients of heart and heart-lung transplants. Two caused acute upper respiratory obstruction necessitating urgent ENT intervention. All patients were receiving immunosuppressive drugs including cyclosporin. The two obstructive cases were adenotonsillar enlargement in a 6-year-old, and a tumour of the tonsil and tongue base with cervical lymph node enlargement in a 32-year-old male. Both were caused by Epstein-Barr Virus-associated lymphoproliferative disorder. The third patient, a 32-year-old female, had a presumed low grade T-cell lymphoma that regressed spontaneously. Histopathological diagnosis of these lympho proliferative disorders after transplantation usually requires immunocytochemistry to distinguish polyclonal proliferative disorders from true lymphoma. Polyclonal lymphoproliferative disorders after transplantation do not usually require aggressive cytoreductive therapy, but respond to simple measures such as the reduction of immunosuppression. PMID- 2230585 TI - Inter-arytenoid glottic bar following intubation. AB - Inter-arytenoid glottic bar is a rare complication of prolonged endotracheal intubation. We present two such cases and their treatment. The aetiology of this complication is multifactorial and involves local factors--local trauma, movement of the endotracheal tube within the larynx, infection, and anatomical influences- together with systemic factors such as in our two cases. The relative importance of these factors is discussed. A comment is also made on the use of a pre operative topogram and the importance of an ENT assessment in patients with airway problems following prolonged intubation. PMID- 2230586 TI - Laryngeal metastasis from colonic adenocarcinoma. AB - Metastases to the larynx from distant primaries are very rare. Usually the secondary lesion comes from an hypernephroma or malignant melanoma. A case of metastatic laryngeal tumour from a colonic adenocarcinoma, occurring in a 59-year old woman, is presented and the routes for laryngeal spread are discussed. The poor survival-rate of these patients justified only conservative surgery. PMID- 2230588 TI - Mid-line presentation of cervical lymphomata. AB - Three cases of lymphoma are reported, all of which presented as a mid-line cervical swelling and appeared to be localised disease. The importance of early removal of such lesions is emphasized. PMID- 2230587 TI - Intralaryngotracheal thyroid. AB - A case of intralaryngotracheal thyroid in a 57-year-old man is presented. The treatment modalities are considered and the previous literature is reviewed. PMID- 2230589 TI - Impaired physicians. An overview and update of the legal issues. PMID- 2230590 TI - The effect of malpractice litigation on patient access to specialty physician services. PMID- 2230591 TI - Physicians' suits against medical malpractice insurers. An analysis of current issues in professional liability insurance litigation. PMID- 2230592 TI - Thiol proteinase inhibitors reverse the increased protein kinase C down regulation and concanavalin A cap formation in polymorphonuclear leukocytes from Chediak-Higashi syndrome (beige) mouse. AB - Protein kinase C (PKC) plays an essential role in intracellular signal transduction for various cell functions, including concanavalin A (Con A)-induced cap formation. This enzyme is known to be proteolysed by calpain, which is a Ca2(+)-dependent thiol proteinase. As reported previously, in polymorphonuclear leukocytes (PMNs) from beige mouse, the model of Chediak-Higashi syndrome, Con A induced cap formation significantly increased compared with that in normal mouse. However, after pretreatment of beige PMNs with the thiol proteinase inhibitors leupeptin or E-64, the capping decreased to normal levels. Meanwhile, Con A induced the translocation of PKC from the cytosolic to membrane fraction within 5 min in both mice, which is essential to the activation of this enzyme. However, after the translocation, an abnormal rapid decline in membrane-bound PKC activity was noted in beige mouse PMNs. Both leupeptin and E-64 also corrected the rapid decline in PKC activity observed in the beige mouse. These findings suggest that the normalization of Con A cap formation in beige mouse PMNs by the thiol proteinase inhibitors is associated with the correction of abnormality in PKC activity. PMID- 2230593 TI - Down-regulation of macrophage I-A expression in tumor-bearing mice. AB - During the subcutaneous growth of a highly metastatic mammary adenocarcinoma line, C3-L4 in C3H/HeJ mice, there was a rapid decline in macrophage I-A expression in vivo. The incidence of I-A+ macrophage subset in the spleen declined from 90% to 10% or less within 5 days of tumor transplantation, with a parallel decline in their absolute number. I-A expression in these cells remained suppressed for a long time until tumors became necrotic and ulcerated. In spite of a low incidence (15-20%) of I-A+ macrophages in the normal peritoneal space, tumor transplantation caused a long-lasting decline in their incidence to one fourth of the original level. Tumor-associated macrophages were predominantly I-A throughout the tumor life span. Thus I-A- macrophages dominated in all anatomical compartments in tumor-bearing mice. Macrophage I-A expression was substantially restored (spleen) or stimulated (peritoneal space and tumor) in tumor-transplanted mice subjected to chronic indomethacin therapy in the drinking water, indicating a reversal of prostaglandin-mediated down-regulation of macrophage I-A expression in situ. Concomitantly, this therapy caused regression of the primary tumors and prevented lung metastasis. These results are relevant to the understanding of tumor-host interactions and its exploitation for immunotherapy. PMID- 2230594 TI - Activated neutrophils induce erythrocyte immunoglobulin binding and membrane protein degradation. AB - Neutrophil-induced alterations in feline erythrocytes were investigated to elucidate the pathogenesis of the erythrocyte destruction associated with inflammatory disease. Incubation of erythrocytes with zymosan-activated neutrophils, at target:effector concentrations of 50:1, resulted in immunoglobulin binding to the erythrocyte membrane and degradation of membrane proteins. Vitamin E and superoxide dismutase/catalase attenuated the immunoglobulin binding. Proteolysis was not prevented by addition of antioxidants or protease inhibitors to the erythrocyte:neutrophil coculture and was not reproduced with chemical oxidation or calcium loading of erythrocytes. PMID- 2230595 TI - Effect of retinoids on the release and gene expression of tumor necrosis factor alpha in human peripheral blood monocytes. AB - The effect of retinoic acid (RA) and retinol (ROH) on the release of tumor necrosis factor (TNF) by human peripheral blood monocytes (HPBM) was determined. HPBM were cultured for various periods of time in either 5% complete (cAB) or delipidized (DLS) AB serum. TNF release (L929 cytolytic assay) in the presence of cAB occurred during the first 3 days of in vitro culture. Delipidization of AB serum completely inhibited the lipopolysaccharide (LPS)-induced release of TNF by HPBM. Addition of RA (0.5 microM) to DLS restored LPS-induced TNF release by HPBM, and supplementation with ROH (1.0 microM) resulted in release of TNF-like activity, but only after 3 days of in vitro culture. The maintenance of TNF release by the addition of exogenous RA after 3 days of in vitro culture suggested that depletion of endogenous RA was partially responsible for loss of TNF-like activity. The levels of endogenous TNF protein and mRNA were not influenced by delipidization of serum and were found to be similar to those of HPBM cultured in the presence of AB serum. TNF protein and mRNA were undetectable in HPBM ROH-treated cell lysates, although cytolytic activity was observed in culture supernatants. These results suggest that retinoids are required for the release of cytolytic factors from HPBM and that non-TNF cytolytic factors may be released by these cells at different stages of maturation. PMID- 2230596 TI - Role of CR3 in induced myelomonocytic recruitment: insights from in vivo monoclonal antibody studies in the mouse. PMID- 2230597 TI - Decreased Fc receptor expression on macrophages following simple hemorrhage as observed by scanning immunoelectron microscopy. AB - Although it is known that macrophage (M phi) functions such as phagocytosis and antigen presentation are depressed following hemorrhage and resuscitation, the mechanism remains unknown. The aim of this study was to determine, using scanning immunoelectron microscopic techniques, whether there is any alteration in the Fc receptors on the M phi after hemorrhage. To study this, male C3H/HeN mice were bled to a mean blood pressure (BP) of 35 mm Hg and maintained at that pressure for 1 hr, then resuscitated with their own blood and adequate fluids. Twenty-four hrs later, Kupffer cells from livers and splenic adherent cells were isolated, incubated for 16 hr, and then exposed to polysterene beads conjugated with antimouse IgG that specifically binds to Fc receptors. The cells were then prepared for observation by scanning electron microscopy. At least 100 cells from each animal were examined. The number of Kupffer cells from posthemorrhage mice that exhibited specific receptor labeling was significantly decreased (41.0 +/- 2.6, P less than 0.05) compared with control (64.2 +/- 7.5). The number of splenic adherent cells from posthemorrhage mice exhibiting specific receptor labeling was also significantly decreased (35.7 +/- 2.5, P less than 0.01) compared with control (61.2 +/- 3.9). The internalization of markers was also seen in some cells. The cause of the decrease in receptor labeling following hemorrhage may be the loss, inactivation, and/or internalization of receptors. Thus the decreased number of functional macrophages may contribute to the depression of antigen presentation and to the enhanced susceptibility to sepsis following hemorrhage. PMID- 2230598 TI - Human recombinant interleukin-2 induces maturation and activation signals for feline eosinophils in vivo. AB - Immunotherapy, with interleukin-2 (IL-2) or IL-2 plus lymphokine-activated killer (LAK) cells, has been used to treat cancer and acquired immunodeficiency syndrome (AIDS) in man. Similarities between feline leukemia virus (FeLV) infection in the cat and human immunodeficiency virus (HIV) infection in man have prompted immunotherapeutic studies in the cat. To develop baseline data on hematological responses to infused IL-2, cats were given daily (1-14 days) i.v. injections of 5 x 10(4) U/kg of recombinant human IL-2 (rHulL-2). Complete blood cell (CBC) counts were done weekly. Red blood cell (RBC), neutrophil, and lymphocyte numbers did not change appreciably over the course of the study. In contrast, rHulL-2 caused an eosinophilia in all but the 1 day treatment group. Treatment for 3 days generated a transient eosinophilia on day 7 that returned to baseline by 3 weeks. Five day and 7 day treatments generated an eosinophilia by day 7 that peaked on day 14 and returned to normal values by day 28. Treatment of cats for 14 days did not increase the magnitude or duration of the eosinophilia beyond the 5 or 7 day treatments. Bone marrow (BM) biopsies from rHulL-2-treated cats revealed a marked selective hyperplasia of eosinophil precursors. In the 5 day treatment group, all maturation stages of eosinophils were elevated by week 1 of treatment. By week 2, the early stages had returned to normal, whereas the late stage cells remained elevated, suggesting an ordered maturation response. Numbers of all eosinophil precursors approximated pretreatment numbers by weeks 3-4. Thus the BM hyperplasia preceded the blood eosinophilia by 1 week, suggesting that an enhanced maturation response of BM eosinophil precursors is a major contributor to the rHulL-2-induced blood eosinophilia. In addition to a maturation signal, rHulL-2 induces a potent activation signal for eosinophils as measured by a decrease in density and an increase in longevity in culture. The significance of the activated eosinophil in the therapeutic or toxicologic response to rHulL-2 infusion is discussed. PMID- 2230599 TI - Lectin binding of rat bone marrow cells during colony-stimulating factor type 1- induced differentiation: soybean agglutinin as a marker of mature rat macrophages. AB - Rat bone marrow cells (BMC) cultured in the presence of murine colony-stimulating factor type 1 (CSF-1) differentiate within 7 days into a cell population containing 96-100% macrophages (M phi). In this study, binding of 10 different fluorescein isothiocyanate (FITC)-conjugated lectins to cultured BMC at various stages of differentiation into M phi was investigated. Only soybean agglutinin (SBA) showed a binding pattern that was significantly correlated to M phi differentiation. Nearly all adherent (A) cells bound SBA. Binding of SBA to nonadherent (NA) cells increased from 20% on day 0 to 80% on day 8. NA cells were separated by means of a fluorescence-activated cell sorter into SBA-, SBA +/-, and SBA+ fractions. On day 0 and day 2, M phi, blast-like cells, eosinophils, and some neutrophils were found in the SBA+ population. From day 4 onwards, the SBA+ fraction contained almost exclusively M phi. Neutrophils and some blasts were found in the SBA- population on days 0 and 2. In the SBA +/- fraction, mainly blasts and lymphocytes were identified. With increasing time of culture, M phi or M phi precursors prevailed also in the SBA-/ +/- cell population. Cells forming colonies in soft agar in the presence of CSF-1 were highly enriched in the SBA +/ fraction. A large number of cells in S-G2/M phases but few colony-forming cells were found in the SBA+ population. Our data suggest that SBA is a useful additional tool to define late stages of M phi differentiation. PMID- 2230600 TI - Bacterial lipopolysaccharide induces release of tumor necrosis factor-alpha from bovine peripheral blood monocytes and alveolar macrophages in vitro. AB - In this study, we demonstrate that freshly adherent bovine monocytes release tumor necrosis factor-alpha (TNF-alpha) in response to stimulation with bacterial lipopolysaccharide (LPS). TNF-alpha was detected using actinomycin D-treated WEHI 164 murine fibrosarcoma cells as targets in an 18 hr cytotoxicity assay. Doses of LPS from 20 ng/ml to 20 micrograms/ml were capable of inducing bovine TNF-alpha. The kinetics of TNF-alpha release from bovine monocytes demonstrated peak levels of cytotoxic activity at 1-3 hr post-LPS treatment, with a subsequent decline to background levels by 18 hr post-LPS treatment. A monoclonal antibody that neutralizes recombinant human TNF-alpha (rHuTNF-alpha) significantly reduced the cytotoxicity of LPS-stimulated bovine monocyte culture supernatants. Size exclusion high-performance liquid chromatography (HPLC) analysis of LPS stimulated monocyte and alveolar macrophage culture supernatants resulted in a molecular weight elution profile similar to that of recombinant human TNF-alpha. These elution profiles are consistent with the presence of multimers of TNF alpha. This is believed to be the first report of the in vitro production of bovine TNF-alpha. PMID- 2230602 TI - Excitability changes in the crustacean motor axons following activity. AB - It has been shown experimentally that the crustacean motor axon is supernormally excitable following a train of action potentials (Zucker 1974). Such a phenomenon can lead to recruitment of terminals which are unexcited at low rates of stimulation. Although currents underlying the crustacean motor axon have been characterized (Connor et al. 1977), it is not known whether this membrane model accounts for a supernormal period, what might cause superexcitability in this model, or how excitability might change during repetitive stimulation. In present study, it is demonstrated that the crustacean motor axon model does predict a supernormal period, that the supernormal period results from slow recovery from inactivation of the transient potassium, or A, current, and that supernormal excitability is enhanced by repetitive stimulation. PMID- 2230601 TI - Modulation of nitrogen oxide synthesis in vivo: NG-monomethyl-L-arginine inhibits endotoxin-induced nitrate/nitrate biosynthesis while promoting hepatic damage. AB - Attempts were made to promote or inhibit nitric oxide (. N = O) synthesis in a murine model of hepatic damage (Corynebacterium parvum followed by lipopolysaccharide; LPS) to determine the role of . N = O in the liver injury. Moderate hepatic damage and increases in circulating NO2-/NO3- levels were detectable after C. parvum alone. Administration of LPS to these mice resulted in severe hepatic damage and acute elevations in circulating nitrogen oxide levels. L-arg had no influence on the C. parvum or LPS-induced changes. NG-monomethyl-L arginine (NMA) had no effect in the absence of LPS, but when given with LPS, a dose-dependent suppression in plasma NO2-/NO3- levels and an increase in liver injury were seen. The NMA-induced changes were partially reversed by the simultaneous administration of L-arg. These findings suggest a protective role for . N = O in this model. PMID- 2230603 TI - Theoretical analysis of the flow of cells over villi of the small intestine. AB - The flow of epithelial cells over villi of mouse small intestine is calculated from equations of cell number balance and irrotational flow. The influence of both villus geometry and crypt distribution about the villus base are studied. Specific, experimentally verifiable predictions are made. PMID- 2230604 TI - Effects of calcium input/output on the stability of a system for calcium regulated viscoelastic strain fields. AB - The Goodwin and Trainor model of pattern generation in calcium-regulated strain fields is studied in the case where calcium input and calcium output processes are involved. It is shown that the properties of the original model may still remain provided that the input-output processes are not unstable. In this last case, despite the eventual stabilizing effect of the calcium exchange term, perturbations of the generalized system can grow and lead to inhomogeneous solutions. Applications to cell differentiation and cell growth are discussed. PMID- 2230605 TI - Nonmedical illness behavior: a model of patients who seek alternatives to allopathic medicine. AB - This project investigated the process by which African-Americans in Chicago decided to access drugless, natural health care systems in conjunction with, or as alternatives to, orthodox medical care. The study focused on African-American users of the drugless, natural health care systems of chiropractic and naprapathy. The data for the study were qualitative and ethnographic, and included over 100 in-depth interviews, extensive field notes based on participant observation and related documents. The findings involved constructing a five stage sequential model that describes the process of conversion to regular use of natural health care. The purpose of this article is to present a model of nonmedical illness behavior that can sensitize health care practitioners to the situational and contingent factors affecting patients' choices. PMID- 2230606 TI - Counteracting nutritional misinformation: a curricular proposal. AB - Health authorities are concerned about community exposure to nutritional misinformation. Adequate education of health professionals in nutritional matters has been proposed as an important strategy for counteracting such misinformation. This paper provides an example of how the undergraduate chiropractic curriculum may be used to facilitate the development of a framework which enables discrimination between nutritional sense and nonsense. It also discusses how student awareness of discrepancies between personal belief, nutritional science and clinical practice reality may be enhanced. PMID- 2230607 TI - Atlantoaxial anomalies with particular emphasis on os odontoideum. AB - Anomalies of the atlantoaxial articulation are discussed with emphasis on os odontoideum. Normal and abnormal embryological and anatomical characteristics are described, as is their relevance upon stability of the upper cervical segments. This paper further discusses and reviews theories pertaining to the congenital and acquired forms of os odontoideum and a case report is presented. Some conclusions are drawn from the presented case report. PMID- 2230608 TI - Radiation induced fracture of the scapula. AB - A case of radiation induced osteonecrosis resulting in a fracture of the scapula in a 76-yr-old female patient with a history of breast carcinoma is presented. Diagnostic imaging, laboratory recommendations and clinical findings are discussed along with an algorithm for the safe management of patients with a history of cancer and musculoskeletal complaints. This case demonstrates the necessity of a thorough investigation of musculoskeletal complaints in patients with previous bone-seeking carcinomas. PMID- 2230609 TI - Code Blue: adolescent health, the crisis and the hope. PMID- 2230610 TI - The experience of a child and adolescent inpatient unit in London. AB - The Mildred Creak Unit of the Hospital for Sick Children, Great Ormond Street, London, England, has been evaluating and treating children and adolescents now for over 16 years. A portion of their valuable experience, with 394 patients reviewed, is presented in this article. Items discussed include: (1) major diagnostic labels utilized and their frequency of use; (2) ages and sex of young people within the major diagnostic categories; and (3) information on discharge status plus average length of stay. This paper affords the reader an opportunity to compare the Mildred Creak Unit experience with his or her own experience, hopefully enhancing further international sharing of child and adolescent data. PMID- 2230611 TI - The legacy of James Edgar Paullin, M.D. AB - The legacy of the man lives on, years after his death. Physicians from his own hospital have held and will hold his former posts as president of the AMA and the American College of Physicians (Harrison Rogers and Nick Davies, respectively). Organizations that he helped start, the Southeastern Clinical Society and the Atlanta Clinical Society, continue to thrive. His high standards of medical care continue from a grandson-in-law (David Watson) and great-grandson (Brooks Lide). To quote from Dr. R. Hugh Wood's letter in 1951: "From the life of Dr. Paullin one may learn to better serve his profession and his country. Possessed of a keen intelligence, he took full advantage of his exceptional educational opportunities, and with vigor and persistence he lived a full life of service as physician, teacher, citizen, and friend." PMID- 2230613 TI - Stepparents and stepchildren: the Phaedra complex. PMID- 2230612 TI - Exertional rhabdomyolysis in two prison inmates. AB - We have reported two cases of exertional rhabdomyolysis which resolved without serious complication. The denial and exclusion of significant historical information initially made the specific etiology of rhabdomyolysis indeterminate in the first case. PMID- 2230614 TI - Access to medical care: a perspective of internal medicine. PMID- 2230615 TI - The evolving role of surgery in the treatment of breast cancer. PMID- 2230617 TI - Smoking cessation strategies for the cardiac patient. AB - Studies involving subjects attempting to discontinue cigarette smoking reveal that long-term success rates remain disappointingly low--in the range of 10 to 33 percent at 1 year. No single method or drug has proved to be a panacea. Serious commitment by the patient is of paramount importance in achieving long-term success. The physician is in a unique position to initiate a patient's attempted cessation, reinforce a patient's resolve, and offer support during the endeavor. Clonidine appears to decrease craving and nicotine gum decreases withdrawal symptoms in many patients. PMID- 2230616 TI - State regulation of abortion upon minors: the Supreme Court permits parental notification statutes. PMID- 2230618 TI - The philosopher as insider and outsider. AB - Philosophers may play the role of insider, e.g., serving as advisor to government commissions, or of outsider, commenting on the work of such commissions. Each role may raise dilemmas. It is argued that as insider the philosopher's primary duties should be to clarify and inform, as well as philosophize with the commissioners, and help them stay on a course in which moral considerations are given their proper weight. Fulfilling these duties means that the philosopher will sometimes have to help produce a weaker intellectual document than he would prefer, or lose a chance to directly promote the public good. The insider philosopher will also have to consider whether it is appropriate for a policy proposal from a commission to differ from much current government policy, and how morally appropriate compromise can be reached among commissioners. Given his understanding of how an insider philosopher should function and how commission reports are constructed, the outsider philosopher can comment both on how close a report comes to being perfect of its type, and how far short of an ideal philosophical analysis even a perfect government report is. It may be appropriate for him to give greater weight to the public good, if his comments are very likely to affect it, than the insider philosopher. Examples for discussion are drawn from government reports on organ transplantation, embryo research, terminating care, and compensation for research subjects. PMID- 2230619 TI - Philosophical integrity and policy development in bioethics. AB - Critically examining what most people take for granted is central to philosophical inquiry. Philosophers who accept positions on policy making commissions, tasks forces, or committees cannot, however, play the same uncompromisingly critical role in this capacity as they do in the classroom or in their personal research or writing. Still, philosophers have much to contribute to such bodies, and they can do so without compromising their integrity or betraying themselves as philosophers. PMID- 2230620 TI - Philosophers and the public policy process: inside, outside, or nowhere at all? AB - Three standard tasks undertaken by applied ethicists engaged in the public policy process are identifying value issues, clarifying concepts and meanings, and analyzing arguments. I urge that these should be expanded to include making specific moral judgments and advocating positions and policies. Three objections to philosophers/ethicists' engagement in the formation of public policy are advanced and evaluated: philosophers necessarily do public policy badly, doing it at all compromises one's integrity as a seeker after truth, and frequently participation is in the service of a repressive status quo that is structured simultaneously to preclude radical change and to co-opt ethicists. Finally, however, I argue that those who would be 'applied ethicists' cannot avoid all participation in some form of a public policy process; that engagement holds the hope as well for improved ethical theory; that the preferred form of participation is frequently from outside of establishment bodies; and that wherever philosophers do involve themselves in policy formulation, this is best done in the expanded sense urged at the outset. PMID- 2230621 TI - Public philosophy: distinction without authority. AB - An assumed core of normative ethical principles may constitute a philosophically proper framework within which public policy should be formulated, but it seldom provides any substantive solutions. To generate public policy on bioethical issues, participants still need to confront underlying philosophical controversies. Professional philosophers' proper role in that process is to clarify major philosophical options, to press wider-ranging consistency questions, and to bring more parties into the philosophical debate itself by arguing for particular substantive claims. Though questions of fact that mediate final policy conclusions frequently fall outside philosophical competence, one sort of fact, lack of political support, should seldom cause philosophers to stand aside; philosophers still have an important role as critics of culture, politics, and profession. They have no authority, however, on even the philosophical presuppositions of public policy. PMID- 2230622 TI - Physician investment and self-referral: philosophical analysis of a contentious debate. AB - A new economic phenomenon, in which physicians refer their patients to ancillary facilities of which they themselves are owners or substantial investors, presents a 'laboratory' for assessing philosophers' potential contributions to public policy issues. In this particular controversy, 'prohibitionists' who wish to ban all such self-referral focus on the dangers that patients and payers may receive or be billed for unnecessary or poor-quality care. 'Laissez-fairists', in contrast, argue that self-referral should be freely permitted, with a reliance on personal ethics and internal professional monitoring to guard against abuse. Undue government regulation, they argue, infringes providers' and patients' economic freedom, and stifles the competition that can yield better quality care at lower prices. As this debate features basic values and large amounts of money, it has been marked by rancorous rhetoric, shallow argument, and muddled reasoning. The philosopher's first contribution, therefore, is to expose simplistic and fallacious arguments, whether empirical, conceptual, moral, or legal. Beyond this the philosopher can help to identify the important values at stake and, perhaps, to identify resolutions that honor those values better than the more simplistic answers proffered previously. For abusive self-referral, as distinguished from kickbacks, the author recommends that civil remedies be favored over criminal prohibitions. She suggests that the doctrine of 'bad faith breach of contract' might appropriately be extended into this new area to provide a powerful means by which aggrieved patients and payers can hold physicians personally accountable for abusive self-referrals. PMID- 2230623 TI - Undetectable anti-bacterial activity of Andrographis paniculata (Burma) wall. ex ness. AB - Andrographis paniculata (Burma) Wall. ex Ness (AP) is a herbal medicine and has been used for therapy of upper respiratory tract infection (URI) as well as acute diarrhea with reported efficacy of 75-100 per cent. To investigate whether anti bacterial activity was responsible for the reported therapeutic success of AP, we carried out a number of studies. The first study was a direct assay of anti bacterial activity of AP suspended in water. The tested pathogens included Salmonella, Shigella, E.coli, gr. A Streptococci and S.aureus. Anti-bacterial activity was not demonstrable even in a solution containing 25,000 mg per litre of crude powder. The second was designed to detect serum bactericidal activity after oral intake of stem and leaves of AP. Ten healthy volunteers were enrolled in the study. They received a single oral dose of AP (1, 2, 3 and 6 g) in a randomized, cross-over manner. The washout period was one week. Blood samples were taken at 0, 1, 2, 4, 8 and 24 hours after ingestion. Serum bactericidal activity was assayed by agar diffusion technique using Bacillus spores and five strains of each pathogen (Shigella, Salmonella typhi, S.aureus and gr. A Streptococci) incubated for 24 hours. Again serum bactericidal activity was not detected in any of the sera tested. In a third study, ninety-six rats were daily fed with high doses of AP ranging 0.12-24 g per kg body wt. for six months before sacrifice. Antibacterial activity was still undetectable when lung parenchyma and liver tissue was placed on culture media containing bacteria tested. In conclusion, anti-bacterial activity of AP is undetectable in our study. PMID- 2230624 TI - The immunodiagnosis of tuberculosis in Thailand. PMID- 2230625 TI - Accuracy of two-dimensional echocardiography in diagnosis of aortic dissection. AB - The usefulness of transthoracic and transabdominal two-dimensional echocardiography (2-D echo) in patients who presented with dilated aorta with or without acute chest pain and/or abdominal pain was assessed for diagnosis of aortic dissection (AD) both acute and chronic forms. The criterion for diagnosis of AD was the constant appearance of undulating motion of abnormal linear echo in the aortic lumen in more than one scan plane. During a 4-year period (1984-1988), a prospective analysis of 16 patients was carried out and the result disclosed that 11 had AD (6 in acute AD, 5 in chronic AD) while the other 5 did not have AD. 2-D echo findings were diagnostic of De Bakey Type I in 7 patients, Type II in one, Type III in two, false negative Type I in one, and true negative in the remaining five. Therefore, the sensitivity was 91 per cent and the positive predictive value was 100 per cent. Thus, our data indicates that 2-D echo is a reliable non-invasive method for diagnosis of AD in either the acute or chronic form and proximal or distal AD. PMID- 2230626 TI - Ciprofloxacin in severe infections. AB - Ciprofloxacin is the most potent post-marketing fluoroquinolone. In vitro activity and pharmacokinetic properties of this agent, together with clinical trials of the drug may be very promising in the treatment of severe infections, especially when the bacteria involved are resistant to other conventional agents. We performed an open clinical trial of this agent in hospitalized patients with severe infections in a university hospital in Bangkok, Thailand. A total of 25 patients were enrolled on the basis of clinical diagnosis of severe bacterial infections. Six of these patients were dropouts (3 of which proved to be non bacterial infections, 2 patients each had only anaerobic infection and nocardiosis. One suffered from a severe psychotic attack). The remaining 19 patients were evaluated. There were 12 males and 7 females, the age ranged from 13 to 77 years old (43.2 +/- 20.1). Most had severe underlying illnesses (17 out of 19). There were 23 infections in 19 patients. Septicemia was the most common infection treated. Other infections included complicated urinary infection, upper respiratory tract infection, skin/skin structure infection. P. aeruginosa was the most common pathogen infected. Other organisms were E.coli, Enterobacter, P.mirabilis, S.aureus, A.antitratus and mycobacterium. Ciprofloxacin was given as an initial 100 mg twice daily as intravenous infusion, and this was switched to an oral form of 500 mg b.i.d./at approximately day 4 to day 6. The overall cure rate was 68 per cent. There were 2 improvements, 2 relapses/reinfections and one failure. Toxic effect included one psychotic attack necessitating discontinuation of the drug. Other adverse drug reactions were mild and transient. These included elevation of transaminase and LDH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230628 TI - Cass scores as a preoperative prediction for recurrences of cervical cancer after radical hysterectomy and pelvic lymphadenectomy at Srinagarind Hospital. AB - Risk factors for recurrence after radical hysterectomy and pelvic lymphadenectomy at Srinagarind Hospital was studied from 218 patients operated between 1976 to June 30, 1988. Four preoperative risk factors i.e., cell types, age, stages and size of the lesions were computed and cross-tabulated with the recurrence rate from the data of the whole patients. The correlation was found to be statistical significant. This scoring system should be called from the first letter of the factor as 'CASS' and used for selection of the patients for radical hysterectomy and pelvic lymphadenectomy. PMID- 2230627 TI - Mechanical ventilation in status asthmaticus: experience with 75 episodes. AB - Mechanical ventilation in 75 out of 560 status asthmaticus episodes during a five year period (1984-1988) at Chulalongkorn Hospital were analyzed. There were 58 patients with an average age of onset of first asthmatic attack of 18.5 years and an average age when requiring mechanical ventilation of 33 years, which is significantly younger than among those who did not require assisted ventilation. At the time of intubation, four patients were in sudden unexpected arrest and 19 patients were urgently ventilated because of respiratory muscle fatigue or carbon dioxide narcosis; the remaining 52 patients required elective mechanical ventilation. The arterial blood gas of 52 patients revealed a pH of 7.11 +/- 0.66, PaCO2 of 58.0 +/- 5.5 mmHg, and HCO3 of 15.0 +/- 5.8 mEg/L. Controlled mechanical ventilation was maintained for a mean of 38.68 hours. Fifty-one patients required intravenous diazepam (average dose = 24.3 mg) and 37 required morphine (average dose = 11.1 mg) for good syncronization in controlling mechanical ventilation. Pneumothorax was the most common complication with four, nine and one episodes occurring prior to, during and after assisted ventilation, respectively. Four, one and two patients developed the complications of pneumonia, atelectasis of the left lung due to mucous plugging and upper gastrointestinal hemorrhage, respectively. There were six patients who died of complications: four of brain anoxia, one of pneumothorax and another of unexplained cause. PMID- 2230629 TI - Epidemiology of cancer in Khon Kaen. AB - The prospective and retrospective data collection of cancer cases in all the hospitals and death certificates in Khon Kaen province were reported as a population-based cancer registry of Khon Kaen province. Liver cancer especially cholangiocarcinoma and cervical cancer lead the group. The age-standardized incidence rate of cancer of Khon Kaen was about 72.4 to 173.3 per 100,000 population per year and it is higher in males than in females. PMID- 2230630 TI - Community-acquired pneumonia in adults at Srinagarind Hospital. AB - A prospective study of community-acquired pneumonia in adults at Srinagarind Hospital, Khon kaen University was conducted from September 1987 to August 1988. Laboratory specimens were tested for bacterial and mycoplasmal culture, CIE for pneumococcal antigen and serological data for mycoplasma and P. pseudomallei. The results supported by clinical data were evaluated. We could identify the pathogens from 62 of 113 cases (55%). P. pseudomallei was the most frequent etiologic agent (32%) and S. pneumoniae was the second (27%). Overall mortality was 21 per cent and it was high in cases with bacteremia and pneumonia due to P. pseudomallei. Sixty-six per cent of the patients had associated diseases. Diabetes mellitus, chronic renal failure and renal calculi were commonly found in patients with pneumonia due to P. pseudomallei. The results of this study showed the relatively high prevalence of P. pseudomallei pneumonia in our region which was different from other reports. PMID- 2230632 TI - 181st meeting of the Society for Endocrinology. 14-16 November 1990, London. Abstracts. PMID- 2230631 TI - Giant cell arteritis. AB - An 80-year-old woman was admitted after a 4 months history of severe headache. Laboratory data revealed elevated ESR, mild anemia and alteration of liver function test. Temporal artery biopsy showed the classical picture of giant cell arteritis. The clinical symptoms and laboratory abnormalities reversed to normal after prednisolone therapy. Although the true prevalence of this disease is unknown in Thailand, previous studies in western countries have revealed that it is not a common disease. GCA may be missed or incorrectly diagnosed in elderly patients with headache and a high ESR. Such a diagnosis can subject the patient to complication of GCA, needless biopsy and serious side effects of therapy with large doses of prednisolone. PMID- 2230633 TI - The history of imitation in learning theory: the language acquisition process. AB - The concept of imitation has undergone different analyses in the hands of different learning theorists throughout the history of psychology. From Thorndike's connectionism to Pavlov's classical conditioning, Hull's monistic theory, Mowrer's two-factor theory, and Skinner's operant theory, there have been several divergent accounts of the conditions that produce imitation and the conditions under which imitation itself may facilitate language acquisition. In tracing the roots of the concept of imitation in the history of learning theory, the authors conclude that generalized imitation, as defined and analyzed by operant learning theorists, is a sufficiently robust formulation of learned imitation to facilitate a behavior-analytic account of first-language acquisition. PMID- 2230634 TI - Reflexes, fictive respiration and cell division in the brain and spinal cord of the newborn opossum, Monodelphis domestica, isolated and maintained in vitro. AB - 1. The entire central nervous system (CNS) was isolated from 1- to 4-day-old newborn South American opossums (Monodelphis domestica). At this stage the CNS has only an embryonic forebrain (two-layered) and no cerebellum and corresponds to a 14-day rat embryo. Its eyes, ears and hind-limbs are only at an early stage of formation. The isolated CNS preparations continue to develop and to produce electrical signals for up to 4 days in oxygenated Krebs' fluid at 23 degrees C. 2. The longitudinal axis of the CNS showed markedly different stages of development. More neuroblast cells were present in the proliferative zone in lumbosacral than in cervical or thoracic regions of the cord. 3. The progeny of dividing cells were labelled in isolated preparations by applying bromodeoxyuridine (BrdU) to the bathing solution for 2 h. Stained precursor cells were observed in CNS that had been left in Krebs' fluid for 4 days before applying BrdU and also in CNS that had been exposed to BrdU shortly after dissection and then left for 4 days. 4. Compound action potentials were evoked from the isolated CNS by stimulation with extracellular electrodes. Compound action potentials increased in amplitude with stronger stimulation and showed discrete peaks of conduction velocity. All electrical activity was eliminated reversibly by 0.1 mumol l-1 tetrodotoxin applied to the bathing solution. Block and recovery occurred with a half-time of approximately 5 min. High concentrations of magnesium (20 mmol l-1) reversibly blocked slower components of the volley. 5. Reflexes in cervical and thoracic segments of the spinal cord continued to function in isolated preparations. Stimulation of a dorsal root evoked bursts of impulses in the appropriate ventral root. Spontaneous and evoked activity in ventral roots was eliminated reversibly by 20 mmol l-1 magnesium. 6. In thoracic segments, spontaneous rhythmical bursts of action potentials were recorded. Burst activity was correlated with respiratory movements of the ribs in semi-intact preparations in which a few ribs and muscles were left attached to the isolated CNS. 7. At raised temperatures of 28 degrees C compared to 23 degrees C both spontaneous and evoked electrical activity were reversibly reduced. 8. Together these results show that the isolated CNS of the newborn opossum survives well in culture. The preparation offers advantages for pharmacological and physiological studies of spinal reflexes, for analysis of the mechanisms underlying rhythmical respiratory activity and for following the time course of CNS development in vitro. PMID- 2230635 TI - Ultrasound-triggered, flight-gated evasive maneuvers in the praying mantis Parasphendale agrionina. I. Free flight. AB - Free-flying male praying mantises Parasphendale agrionina (Gerst.) perform evasive maneuvers when stimulated by ultrasound and when attacked by hunting, echolocating bats. They do not, however, respond in any way when standing on a substratum. The maneuvers are graded in intensity with distance from the sound source: far from the source they are simple turns, whereas close to the source they are steep diving turns or spirals. The maneuvers are made under power, and the male's velocity doubles to almost 4 m s-1 by the end of a steep dive. The mantis does not show any directional preference. The behavioral threshold of 64 dB SPL and minimum latency to course change of 125 ms indicate that these mantises should have adequate time to evade bats using calls of greater than 85 90 dB SPL (at 10 cm). In field experiments with wild, hunting bats, P. agrionina successfully evaded capture in all five attacks to which they responded with evasive maneuvers. Out of three attacks on P. aeruginosa and three on a normally non-responding mantis, Miomantis paykullii Stal, in which there were no evasive maneuvers, the mantis was captured in five cases. PMID- 2230636 TI - Effects of taurine on Ca2(+)-dependent force development of skinned muscle fibre preparations. AB - The effects of the naturally occurring amino acid taurine (2-aminoethanesulphonic acid) on isometric force development were investigated using skinned muscle fibre preparations. In atrial and ventricular pig heart muscles, as well as in fibres of slow abdominal extensor muscle of crayfish, an increase of submaximal isometric force was observed in Ca2(+)-activated skinned fibre preparations at physiological concentrations of taurine. The maximal isometric force remained unaffected in all preparations. It is assumed that taurine increases the Ca2+ sensitivity of the force-generating myofilaments in mammalian hearts and crustacean slow skeletal muscle fibres. PMID- 2230637 TI - Effect of activity on performance and morphology in ischaemic rat slow muscles. AB - Muscle performance and structure was studied in rat soleus muscle with limited blood supply in combination with chronic muscle stimulation. Blood supply to the lower leg was restricted by ligation of the common iliac artery, electrodes were implanted in the vicinity of the sciatic nerve and ankle flexors were denervated. Three days later, soleus and gastrocnemius muscles were stimulated at 4 Hz four times a day for a period of 20 min with 2 h intervals between stimulations; this procedure was continued for 4 days. Muscle performance, histochemistry and ultrastructure were studied on the eighth day after operation in these muscles and in ischaemic unstimulated muscles with denervated ankle flexors. Both were compared with control animals. Muscles with limited blood supply developed less isometric twitch tension than control muscles (peak twitch tension in ischaemic muscle was 60.3 +/- 4.8 g g-1 muscle, mean +/- S.E.M., compared to 79.7 +/- 6.9 g g-1 in control muscle; tensions after 5 min contraction were 54.5 +/- 5.5 g g-1 in ischaemic muscle compared to 70.6 +/- 6 g g-1 in controls). Stimulated muscles with limited blood supply had higher peak (85 +/- 16.6 g g-1) and final (87 +/- 12 g g-1) tensions, and also fatigued less than muscles with limited blood supply but no stimulation. Histochemical estimation of capillary density (by staining for alkaline phosphatase) and slow (SO) and fast (FOG) fibres (by myosin ATPase staining) revealed similar capillary to fibre ratios (2.5) and a similar proportion of FOG fibres (around 18%) in all muscles. The proportion of glycogen depleted fibres (estimated from the periodic acid Schiff reaction, PAS) in muscles removed from animals 10 min after a 5 min period of isometric twitches was significantly lower in ischaemic muscles (45.1 +/- 1.9%) than in control (80.5 +/- 1.5%) or chronically stimulated ischaemic muscles (67.3 +/- 4.0%). Electron microscopy showed disorganised myofibrils with Z-line streaming in 7.48 +/- 3.04% of fibres in muscles with limited blood supply. Swollen and degenerated mitochondria, dilated sarcoplasmic reticulum and areas of disrupted sarcolemma were also observed. Stimulated ligated muscles showed a significantly lower proportion of fibres with disorganised filaments (0.65 +/- 0.32%) and other signs of damage were much less frequent. The reduced damage and improved performance of chronically stimulated slow muscle may be the result of improved microcirculation, preventing accumulation of lactate. PMID- 2230638 TI - Effects of prestretch at the onset of stimulation on mechanical work output of rat medial gastrocnemius muscle-tendon complex. AB - Work output of rat gastrocnemius medialis (GM) muscle (N = 5) was measured for stretch-shortening contractions, in which initiation of stretch occurred prior to the onset of activation, and for contractions with an isometric prephase. Duration of the active prephase (prestretch and pre-isometric) varied from 20 to 200 ms. Subsequent shortening (from optimum length + 4 mm to optimum length -2mm) lasted 150 ms. Stretch velocities of 5, 10 and 20 mm s-1 were used, and the shortening velocity was 40 mm s-1. The effects of several combinations of active stretch duration and active stretch amplitude were compared. Using force compliance characteristics, the work of the contractile element (CE), elastic energy storage and release of the undamped series elastic component (SEC) were distinguished. During shortening, an extra amount of work output was produced, induced by active stretch, of which the largest contribution (70-80%) was due to higher elastic energy release. Enhancement of the storage and utilization of elastic energy during the stretch-shortening cycle, caused by higher transition point forces (i.e. force at onset of shortening), increased with active stretch amplitude and was associated with a net loss of work, probably due to cross bridge detachment during active stretch. Net work over the stretch-shortening cycle remained positive for all prestretch contractions, indicating that when a muscle performs this type of contraction, it is able to contribute to work performance on body segments. It is concluded that, in stretch-shortening movements of rat GM muscle, maximal positive work output is incompatible with maximal net work output. Consequences for complex movements in vivo are discussed. PMID- 2230639 TI - Ultrasound-triggered, flight-gated evasive maneuvers in the praying mantis Parasphendale agrionina. II. Tethered flight. AB - In tethered flight, Parasphendale agrionina (Gerst.) males respond to ultrasonic stimuli with a unique suite of behaviors that includes full extension of the forelegs, strong dorsiflexion of the abdomen, a head roll, a 5% decrease in wingbeat frequency and a 33% increase in forewing excursion. Latency for the foreleg extension averages 66 ms while the latency to onset of yaw is 174 ms. The direction of the turn is unrelated to the location of the speaker. Yaw magnitude and latency are only weakly related to sound pressure level, and variability in these and other parameters is high. The behavior shows moderately sharp tuning to 40-60 kHz with a lowest mean threshold of 60 dB SPL. A male will not respond to ultrasound unless in flight, and the context-gating is independent of sensory input from the tarsi. Several components of the in-flight evasive behavior resemble defensive displays on the ground, and we suggest that this mantis has responded to predation pressure from bats with both flight-derived maneuvers and an aerial deimatic display. PMID- 2230640 TI - Transient behavior of sea urchin sperm flagella following an abrupt change in beat frequency. AB - Within the approximate range of 30-80 Hz, the flagellar beat frequency of a sea urchin sperm held by its head in the tip of a micropipet is governed by the vibration frequency of the micropipet. We have imposed abrupt changes in flagellar beat frequency by changing the vibration frequency of the micropipet within this range and used a high-speed video system to analyze the flagellar wave parameters during the first few cycles following the change. Our results demonstrate that the various flagellar beat parameters differ in the time they take to adjust to the new conditions. The initiation rate of new bends at the base is directly governed by the frequency of the vibration and changes immediately to the new frequency. The length and the propagation velocity of the developed bends become adjusted to the new conditions within approximately 1 beat cycle, whereas the bend angles take more than 4 beat cycles to attain their new steady-state value. Bends initiated shortly before the change in frequency occurs attain a final length and angle that depends on the relative durations of growth at the old and new frequencies. Our results suggest that the flagellar wavelength and bend angle are regulated by different mechanisms with the second not being directly dependent on bend initiation. PMID- 2230641 TI - Inhibition of escape tailflip in crayfish during backward walking and the defense posture. PMID- 2230642 TI - Failure of clonal deletion in neonatally thymectomized mice: tolerance is preserved through clonal anergy. AB - Self-tolerance is achieved in part through intrathymic deletion of self-reactive T cells. The necessity of the thymus for this process is suggested by the development of autoimmune diseases in neonatally thymectomized (neoTx) mice and by the failure of clonal deletion in nude mice. Indeed, the present study demonstrates that neonatal thymectomy on day 3 after birth results in the failure of clonal deletion of V beta 11+ T cells in BALB/c mice and V beta 5+ and V beta 6+ T cells in DBA/2 mice. However, these potentially autoreactive cells are nonfunctional as measured by proliferation and lymphokine production after stimulation with appropriate anti-V beta mAbs or stimulator cells. It appears that this induction of nonresponsiveness may have occurred extrathymically: the early neonatal thymus (presumably the source of the peripheral T cells observed in neoTx mice) also contains T cells with self-reactive receptors, but these cells are fully functional. Therefore, neonatal thymectomy aborts deletion of self-reactive T cells, but self-tolerance is maintained through functional inactivation of potentially self-reactive clones. PMID- 2230643 TI - Low dosages of interleukin 1 protect mice against lethal cerebral malaria. AB - In cerebral malaria, pathological changes can be found in the brain of infected people and in the brain of Plasmodium berghei-infected mice. The pathogenesis of cerebral malaria in mice is believed to be due to an immunopathological reaction giving rise to an excessive production of cytokines such as interferon gamma (IFN gamma) and tumor necrosis factor (TNF). We find that low doses of interleukin 1 (IL-1) protect mice against cerebral malaria; IL-1 also inhibits parasitemia. The IL-1 effect on parasitemia was not observed in nude mice and was at least partly reversed in mice treated with IL-1 in combination with antibody to IFN-gamma, indicating the involvement of T cells. Mice protected against development of cerebral malaria by IL-1 treatment developed the syndrome when TNF was given as observed in control infected mice or infected mice treated with inactivated IL-1. PMID- 2230644 TI - Prooxidant activity of transferrin and lactoferrin. AB - Acceleration of the autoxidation of Fe2+ by apotransferrin or apolactoferrin at acid pH is indicated by the disappearance of Fe2+, the uptake of oxygen, and the binding of iron to transferrin or lactoferrin. The product(s) formed oxidize iodide to an iodinating species and are bactericidal to Escherichia coli. Toxicity to E. coli by FeSO4 (10(-5) M) and human apotransferrin (100 micrograms/ml) or human apolactoferrin (25 micrograms/ml) was optimal at acid pH (4.5-5.0) and with logarithmic phase organisms. Both the iodinating and bactericidal activities were inhibited by catalase and the hydroxyl radical (OH.) scavenger mannitol, whereas superoxide dismutase was ineffective. NaCl at 0.1 M inhibited bactericidal activity, but had little or no effect on iodination. Iodide increased the bactericidal activity of Fe2+ and apotransferrin or apolactoferrin. The formation of OH.was suggested by the formation of the OH.spin trap adduct (5,5-dimethyl-1-pyroline N-oxide [DMPO]/OH)., with the spin trap DMPO and the formation of the methyl radical adduct on the further addition of dimethyl sulfoxide. (DMPO/OH).formation was inhibited by catalase, whereas superoxide dismutase had little or no effect. These findings suggest that Fe2+ and apotransferrin or apolactoferrin can generate OH.via an H2O2 intermediate with toxicity to microorganisms, and raise the possibility that such a mechanism may contribute to the microbicidal activity of phagocytes. PMID- 2230645 TI - Distinct fates of self-specific T cells developing in irradiation bone marrow chimeras: clonal deletion, clonal anergy, or in vitro responsiveness to self-Mls 1a controlled by hemopoietic cells in the thymus. AB - Elimination of potentially self-reactive T lymphocytes during their maturation in the thymus has been shown to be a major mechanism in accomplishing self tolerance. Previous reports demonstrated that clonal deletion of self-Mls-1a specific V beta 6+ T lymphocyte is controlled by a radiosensitive I-E+ thymic component. Irradiation chimeras reconstituted with I-E- bone marrow showed substantial numbers of mature V beta 6+ T cells despite host Mls-1a expression. Analysis of the functional properties of such chimeric T cells revealed a surprising variability in their in vitro reactivity to host Mls-1a, depending on the H-2 haplotype of stem cells used for reconstitution. In chimeras reconstituted with B10.S (H-2s) stem cells, mature V beta 6+ lymphocytes were present but functionally anergic to host-type Mls-1a in vitro. In contrast, in chimeras reconstituted with B10.G (H-2q) bone marrow, nondeleted V beta 6+ cells were highly responsive to Mls-1a in vitro. These findings suggest that clonal anergy of V beta 6+ cells to self-Mls-1a may be controlled by the affinity/avidity of T cell receptor interactions with bone marrow-derived cells in the thymus depending on the major histocompatibility complex class II molecules involved. Furthermore, chimeras bearing host (Mls-1a)-reactive V beta 6+ cells did not differ clinically from those with anergic or deleted V beta 6+ cells and survived more than one year without signs of autoimmune disease. Interestingly, their spleen cells had no Mls-1a stimulatory capacity in vitro. Therefore, regulation at the level of antigen presentation may be an alternative mechanism for maintenance of tolerance to certain self-antigens such as Mls-1a. PMID- 2230646 TI - A monoclonal antibody (8H3) that binds to rat T lineage cells and augments in vitro proliferative responses. AB - A murine monoclonal antibody, designated 8H3, recognizes a cell surface antigen expressed exclusively on rat T lineage cells. 8H3 antibody immunoprecipitated 180 , 120-, and 90-kD components from rat thymocytes as well as splenic T cells under nonreducing conditions. 8H3 antibody specifically inhibited the binding of thymocytes to fibronectin. Furthermore, binding of rat thymocytes to immobilized synthetic peptide Gly-Arg-Gly-Asp-Ser-Pro-Cys-BSA was inhibited by 8H3 antibody as was Gly-Arg-Gly-Asp-Ser-Pro-Cys, but not by Gly-Arg-Ala-Asp-Ser-Pro-Lys or Gly Arg-Gly-Glu-Ser-Pro. Crosslinking of 8H3 antigen on double-negative thymocytes and adult thymocytes, as well as splenic T lymphocytes by 8H3 antibody and F(ab')2 fragments of goat antibodies to mouse immunoglobulin, led to an increase in the concentration of cytoplasmic free Ca2+ due to the release of Ca2+ from intracellular stores as well as the influx of Ca2+ from extracellular sources. Expression of interleukin 2 receptor and subsequently cell proliferation was observed upon incubation of thymocytes and splenic T cells with 8H3 antibody. Furthermore, 8H3 antibody induced the proliferation of double-negative thymocytes. These data collectively indicated that a cell surface antigen, 8H3, is involved in not only cell adhesion but also involved in the expression of immature as well as mature thymocytes. PMID- 2230647 TI - Suppression of developmental anomalies by maternal macrophages in mice. AB - We tested whether nonspecific tumoricidal immune cells can suppress congenital malformations by killing precursor cells destined to cause such defects. Pretreatment of pregnant ICR mice with synthetic (Pyran copolymer) and biological (Bacillus Calmette-Guerin) agents significantly suppressed radiation- and chemical-induced congenital malformations (cleft palate, digit anomalies, tail anomalies, etc.). Such suppressive effects were associated with the activation of maternal macrophages by these agents, but were lost either after the disruption of activated macrophages by supersonic waves or by inhibition of their lysosomal enzyme activity with trypan blue. These results indicate that a live activated macrophage with active lysosomal enzymes can be an effector cell to suppress maldevelopment. A similar reduction by activated macrophages was observed in strain CL/Fr, which has a high spontaneous frequency of cleft lips and palates. Furthermore, Pyran-activated maternal macrophages could pass through the placenta, and enhanced urethane-induced cell killing (but not somatic mutation) in the embryo. It is likely that a maternal immunosurveillance system eliminating preteratogenic cells allows for the replacement with normal totipotent blast cells during the pregnancy to protect abnormal development. PMID- 2230648 TI - Characterization of a receptor for interleukin 5 on human eosinophils: variable expression and induction by granulocyte/macrophage colony-stimulating factor. AB - Interleukin 5 (IL-5) acts on eosinophil differentiation and activation, suggesting the existence of a membrane receptor for IL-5 on eosinophils. Here, we report that 125I-labeled recombinant human IL-5 bound, at 4 degrees C, to high affinity receptors on human eosinophils. The association constant was higher for hypodense eosinophils (1.93 x 10(9) M-1) than for normodense cells (0.39 x 10(9) M-1), with a closely related number of receptor sites per cell. No specific binding occurred on neutrophils. The specific binding of IL-5 was induced by overnight incubation at 37 degrees C of human eosinophils with granulocyte/macrophage (GM)-CSF. The levels of increase were significantly higher for normodense than for hypodense eosinophils, suggesting a previous in vivo activation of the later subpopulation by GM-CSF. IL-3 was ineffective by itself but synergistically enhanced the effect of GM-CSF. Specificity studies showed that the binding of 125I-labeled IL-5 was inhibited by IL-5, but not by other cytokines, on human eosinophils. These results show the existence of a specific binding site for IL-5 on human eosinophils with a variable affinity on eosinophil hypodense or normodense subpopulations, as previously reported for other membrane receptors. PMID- 2230649 TI - Differences defined by bone marrow transplantation suggest that lpr and gld are mutations of genes encoding an interacting pair of molecules. AB - Homozygosity for either of the lymphoproliferation (lpr) or generalized lymphoproliferative disease (gld) mutations of mice causes the development of systemic lupus erythematosus-like autoimmune syndromes that are characterized by severe lymphadenopathy and highly elevated serum immunoglobulin levels. Although the mutations are nonallelic, analysis of homozygous lpr/lpr and gld/gld mice on the same strain background has indicated that the pathology and severity of the autoimmune syndromes induced by these mutations are indistinguishable. To explain this, it has previously been suggested that lpr and gld may represent mutations in molecules involved in sequential steps of an intracellular metabolic pathway of T cells. We have now investigated the behavior of both lpr and gld in a variety of bone marrow chimeras and have found that functional differences between lpr and gld become apparent after bone marrow transfer. Transfer of lpr/lpr bone marrow to irradiated congenic +/+ recipients caused the development of a graft-vs.-host-like lymphoid wasting syndrome, whereas transfer of gld/gld bone marrow to +/+ recipients resulted in development of a gld-like autoimmune syndrome. Additionally, gld/gld hosts behaved like +/+ hosts irrespective of the genotype of the donor bone marrow, whereas lpr/lpr hosts behaved unlike +/+ hosts when reconstituted with either lpr/lpr, gld/gld, or +/+ bone marrow. These are the first clear differences between these two mutations yet described. Our studies indicate that the molecule altered by the gld mutation is expressed only by bone marrow-derived cells, whereas the molecule altered by the lpr mutation is expressed by both bone marrow-derived cells and by one or more peripheral radioresistant cell populations. To reconcile these differences with the fact that homozygous lpr/lpr and gld/gld mice are indistinguishable, we suggest an alternative model for the relationship between the lpr and gld mutations in which the two molecules affected represent an interacting ligand-receptor pair expressed by different cells. PMID- 2230650 TI - Coding sequences of the tal-1 gene are disrupted by chromosome translocation in human T cell leukemia. AB - The tal-1 proto-oncogene encodes a helix-loop-helix DNA-binding protein that has been implicated in the formation of T cell acute lymphoblastic leukemia (T-ALL). Patients with T-ALL harbor structural rearrangements of tal-1 that result from either local DNA deletion or t(1;14)(p34;q11) chromosome translocation. By analyzing t(1;14)(p34;q11) chromosomes from a series of patients, we have now identified a discrete region of tal-1 wherein most of the translocation breakpoints occur. Moreover, mapping of tal-1 genomic DNA revealed that coding exons are situated on both sides of the t(1;14)(p34;q11) major breakpoint region. Hence, the translocated allele of tal-1 is truncated in a manner that reduces its amino acid coding potential. PMID- 2230651 TI - Eosinophilia in transgenic mice expressing interleukin 5. AB - Experiments in vitro suggest that although interleukin 5 (IL-5) stimulates the late stages of eosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the IL-5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two of which with 8 and 49 transgene copies, are described in detail. These mice appeared macroscopically normal apart from splenomegaly. Eosinophils were at least 65- and 265-fold higher in blood from transgenics, relative to normal littermates, and approximately two- or sevenfold more numerous relative to blood from mice infected with the helminth Mesocestoides corti. Much more modest increases in blood neutrophil, lymphocyte, and monocyte numbers were noted in transgenics, relative to normal littermates (less than threefold). Thus IL-5 in vivo is relatively specific for the eosinophil lineage. Large numbers of eosinophils were present in spleen, bone marrow, and peritoneal exudate, and were highest in the line with the greatest transgene copy number. Eosinophilia was also noted in histological sections of transgenic lungs, Peyer's patches, mesenteric lymph nodes, and gut lamina propria but not in other tissues examined. IL-5 was detected in the sera of transgenics at levels comparable to those seen in sera from parasite-infected animals. IL-3 and granulocyte/macrophage colony stimulating factor (GM-CSF) were not found. IL-5 mRNA was detected in transgenic thymus, Peyer's patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics. Bone marrow from transgenic mice was rich in IL-5-dependent eosinophil precursors. These data indicate that induction of the IL-5 gene is sufficient for production of eosinophilia, and that IL-5 can induce the full pathway of eosinophil differentiation. IL-5 may therefore not be restricted in action to the later stages of eosinophil differentiation, as suggested by earlier in vitro studies. PMID- 2230652 TI - The T alpha 2 nuclear protein binding site from the human T cell receptor alpha enhancer functions as both a T cell-specific transcriptional activator and repressor. AB - T cell-specific expression of the human T cell receptor alpha (TCR-alpha) gene is regulated by the interaction of variable region promoter elements with a transcriptional enhancer that is located 4.5 kb 3' of the TCR-alpha constant region (C alpha) gene segment. The minimal TCR-alpha enhancer is composed of two nuclear protein binding sites, T alpha 1 and T alpha 2, that are both required for the T cell-specific activity of the enhancer. The T alpha 1 binding site contains a consensus cAMP response element (CRE), and binds a set of ubiquitous nuclear proteins. The T alpha 2 binding site does not contain known transcriptional enhancer motifs. However, it binds at least two nuclear protein complexes, one of which is T cell specific. We now report that although the T alpha 2 nuclear protein binding site displays transcriptional activator activity in the context of the TCR-alpha enhancer, this site alone can function as a potent, T cell-specific transcriptional repressor when positioned either upstream, or downstream of several heterologous promoter and enhancer elements. These results demonstrate that a single nuclear protein binding site can function as a T cell-specific transcriptional activator or repressor element, depending upon the context in which it is located. PMID- 2230653 TI - Disappearance of certain acidic organelles (endosomes and Langerhans cell granules) accompanies loss of antigen processing capacity upon culture of epidermal Langerhans cells. AB - Freshly isolated epidermal Langerhans cells (LC) can actively process native protein antigens, but are weak in sensitizing helper T cells. During culture, when LC mature into potent immunostimulatory dendritic cells, T cell sensitizing capacity develops but antigen processing capacity is downregulated. Processing of exogenous antigens for class II-restricted antigen presentation involves acidic organelles. We used the DAMP-technique to monitor acidic organelles at the ultrastructural level in fresh, as well as cultured, mouse and human LC. We observed that the loss of antigen processing capacity with culture of LC was reflected by the disappearance of certain acidic organelles, namely endosomes (particularly early ones), and the hitherto enigmatic LC granules ("Birbeck Granules"). Our findings support the notion that endosomes are critical for antigen processing and suggest that LC granules might be involved as well. PMID- 2230654 TI - Migration and maturation of Langerhans cells in skin transplants and explants. AB - The behavior of Langerhans cells (LC) has been examined after skin transplantation and in an organ culture system. Within 24 h (and even within 4 h of culture), LC in epidermal sheets from allografts, isografts, and explants dramatically increased in size and expression of major histocompatibility complex class II molecules, and their numbers were markedly decreased. Using a new procedure, dermal sheets were then examined. By 24 h, cells resembling LC were found close to the epidermal-dermal junction, and by 3 d, they formed cords in dermal lymphatics before leaving the skin. In organ culture, the cells continued to migrate spontaneously into the medium. These observations establish a direct route for migration of LC from the epidermis into the dermis and then out of the skin. These processes are apparently induced by a local inflammatory response, and are independent of host-derived mediators. The phenotype of migratory cells was then examined by two-color immunocytochemistry and FACS analysis. The majority of migratory leukocytes were Ia+ LC, the remainder comprised Thy-1+, CD3+, CD4-, CD8- presumptive T cell receptor gamma/delta+ dendritic epidermal cells, which clustered with the LC, and a small population of adherent Ia-, FcRII+, CD11a/18+ macrophages. In contrast to the cells remaining within the epidermis of grafted skin at 1 d, the migratory cells were heterogeneous in phenotype, particularly with respect to F4/80, FcRII, and interleukin 2 receptor alpha expression, which are useful markers to follow phenotypic maturation of LC. Moreover, cells isolated from the epidermis of grafts at 1 d were more immunostimulatory in the allogeneic mixed leukocyte reaction and oxidative mitogenesis than LC isolated from normal skin, though less potent than spleen cells. The day 1 migratory cells were considerably more immunostimulatory than spleen cells, and day 3-5 migratory cells even more so, suggesting that functional maturation continues in culture. Thus, maturation of LC commences in the epidermis and continues during migration, but the cells do not need to be fully mature in phenotype or function before they leave the skin. In vivo, the migration of epidermal LC via the dermis into lymphatics and then to the draining nodes, where they have been shown previously to home to T areas, would provide a powerful stimulus for graft rejection. PMID- 2230655 TI - Engagement of major histocompatibility complex class II molecules induces sustained, lymphocyte function-associated molecule 1-dependent cell adhesion. AB - Antigenic stimulation is associated with enhanced adhesion between T cells and antigen-presenting cells (APC). Binding of ligands to the T cell antigen receptor activates the adhesion function of lymphocyte function-associated molecule 1 (LFA 1; CD11a/CD18). We demonstrate here that ligand binding to major histocompatibility complex class II (Ia) molecules also activates LFA-1 function, providing a reciprocal mechanism for the induction of adhesion between T cells and Ia+ APC. Adhesion was affected by a qualitative change in LFA-1 molecules and was reversed by the protein kinase C inhibitor sphingosine. These results define a novel role for Ia molecules as signal transducing receptors that regulate LFA-1 dependent adhesion via a putative, Ia-coupled protein kinase(s). PMID- 2230657 TI - Evidence for an association between the discriminative stimulus and the response outcome association in instrumental learning. AB - In 4 experiments, rats received 1 of several outcomes for engaging in various instrumental responses in the presence of discriminative stimuli. Discriminative stimuli shared some response-outcome relations but not others. When a response was subsequently extinguished in the presence of 1 discriminative stimulus, that produced relatively more decrement in responding in other stimuli that shared the same response-outcome relation. Other discriminative stimuli, in the presence of which that response had been reinforced by other outcomes and in which the original outcome had reinforced another response, were less affected. Moreover, postextinction devaluation of that outcome suggested that the particular response outcome relation extinguished had undergone decrement. These results suggest that discriminative stimuli have relatively specific associations with the response outcome relations that obtain in their presence. PMID- 2230656 TI - Aspergillus fumigatus allergen I, a major IgE-binding protein, is a member of the mitogillin family of cytotoxins. AB - A major 18-kD IgE-binding protein from Aspergillus fumigatus (Asp fI) has been purified. Partial amino acid sequencing of Asp f I showed extensive sequence homology (95%) between Asp fI and a cytotoxin (mitogillin) produced by A. restrictus. Crossinhibition radioimmunoassay using murine monoclonal antibody and human IgG and IgE antibodies showed that Asp fI and mitogillin were antigenically indistinguishable. Furthermore, both proteins inhibited protein synthesis in vitro by greater than 90%. Asp fI was expressed in A. fumigatus but not in seven other Aspergillus species. The results suggest that Asp fI could play a dual role in the pathogenesis of A. fumigatus-related diseases by promoting colonization through cytotoxic activity and by causing inflammatory reactions involving IgE antibodies. PMID- 2230658 TI - Schedule-induced kinesic and taxic behavioral stereotypy in the pigeon. AB - Two experiments explored the functional character of 2 schedule-induced interim behaviors (pacing and retreat) and 1 terminal behavior (keypecking) that developed on fixed-time (FT) schedules of food delivery with a keylight that increased in brightness throughout the interstimulus interval. In Experiment 1, this ramp procedure was compared with a less discriminable ramp, and FT and Random Time (RT) procedures without a signal. Decreased discriminability expanded keypecking in the trial. The FT schedule eliminated only keypecking and the RT procedure eliminated keypecking and retreat while pacing remained. In Experiment 2, predictive and unpredictive ramps were added to the RT procedure. The data suggest that schedule-induced stereotypy can be divided into kinesic stereotypy (pacing), which arises from repeated reinforcer presentations, and taxic stereotypy, which is tied to an increase (keypecking) or decrease (retreat) in the momentary probability of reinforcement. PMID- 2230659 TI - Defeat-induced hypoalgesia in the rat: effects of conditioned odors, naltrexone, and extinction. AB - In Experiment 1, male rats were either defeated as a colony intruder by alpha conspecifics or had no defeat experience, and 24 hr later they were given a paw injection of formalin prior to observational tests with or without alpha-colony odors. The combination of defeat and tests with these odors produced conditioned hypoalgesia (i.e., a suppression in paw licking) and freezing. In Experiment 2, defeated rats were given either an injection of naltrexone or saline prior to defeat and 24 hr later prior to testing. An injection of naltrexone prior to defeat increased freezing during defeat and later testing. In contrast, naltrexone during testing did not affect freezing but significantly reduced hypoalgesia. In Experiment 3, a 12-hr exposure session with alpha-colony odors extinguished hypoalgesia in previously defeated rats. These findings are discussed in terms of associative, opioid/nonopioid, and adaptive evolutionary processes. PMID- 2230660 TI - Selective associations in the observational conditioning of fear in rhesus monkeys. AB - Three experiments explored the issue of selective associations in the observational conditioning of fear. Experiment 1 results indicated that observer rhesus monkeys acquired a fear of snakes through watching videotapes of model monkeys behaving fearfully with snakes. In Experiment 2, observers watched edited videotapes that showed models reacting either fearfully to toy snakes and nonfearfully to artificial flowers (SN+/FL-) or vice versa (FL+/SN-). SN+/FL- observers acquired a fear of snakes but not of flowers; FL+/SN- observers did not acquire a fear of either stimulus. In Experiment 3, monkeys solved complex appetitive discriminative (PAN) problems at comparable rates regardless of whether the discriminative stimuli were the videotaped snake or the flower stimuli used in Experiment 2. Thus, monkeys appear to selectively associate snakes with fear. PMID- 2230661 TI - Thrombocytes as interfering factors in clinical chemistry. PMID- 2230662 TI - Isotachophoretic determination of urea-ammonium in plasma: a candidate reference method. AB - Separation and determination of sample constituents by capillary isotachophoresis are entirely based on physical phenomena. The method has therefore been proposed as a universal reference method for ionic constituents. The present paper shows that even neutral species can be adequately determined after suitable preceding reactions. Urea was completely hydrolysed by urease (EC 3.5.1.5) to ammonia and bicarbonate, followed by direct measurement of the ammonium ion concentration by capillary isotachophoresis. Standard Reference Material No. 912a urea (National Bureau of Standards) was used as a primary standard. The analytical linear range of the method extends to 64 mmol urea per litre. The precision of the method was in the range of 1.05-2.64% (CV) and the analytical recovery of added urea was excellent (99.4%, SD 1.13%). Further proof of accuracy was obtained by analysing the NBS human reference serum (standard reference material 909). The mean result by the capillary isotachophoretic method, 9.52 +/- 0.085 mmol/l, agrees well with the reference value, 9.64 mmol/l. The results obtained by capillary isotachophoresis showed good agreement with those obtained by the coupled-enzyme method (r = 0.995). PMID- 2230663 TI - Comparison of two immunoinhibitory methods with agarose gel-electrophoresis for measuring the MB isoenzyme of creatine kinase in serum from cases of suspected myocardial infarction. AB - Two immunoinhibitory methods for measuring creatine kinase-MB (a dry chemical and a wet chemical method) were compared with the commonly used agarose gel electrophoretic method, using 563 serum samples from 235 patients with suspected acute myocardial infarction. Comparison of the electrophoretic and the dry chemistry methods showed the linear relationship: electrophoretic method = -6.5 U/l + 1.22 x dry chemistry method, r = 0.943. For the wet chemistry method the relationship was: electrophoretic method = -7.2 U/l + 1.19 x wet chemistry method, r = 0.854. Parallel determinations of total creatine kinase were also done and the methods were virtually identical in performance. Compared with the electrophoretic method (which showed a 15% prevalence of acute myocardial infarction), these classifications showed sensitivities of 0.92 and 0.67 and specificities of 0.94 and 0.99 (dry and wet chemistry, respectively; using methods recommended by the manufacturers). After optimization of discriminators the sensitivity was increased to 0.94/0.92 and the specificity to 0.99/0.99. PMID- 2230664 TI - Aluminium binding to serum constituents: a role for transferrin and for citrate. AB - The binding of aluminium in rat serum was studied. Rats were loaded intraperitoneally with different doses of aluminium(III)chloride 4 times during one week, before being killed by cardiac puncture. One ml of serum was applied to a Sephacryl S-200 SF column and 70 fractions were collected. In the collected fractions, the distribution of aluminium was measured and compared with the concentrations of total protein, transferrin, and citrate. The presence of a high molecular weight aluminium-complex in serum is confirmed. Although a possible role for albumin cannot be excluded, it is most likely that transferrin plays a role as a carrier for biological transport of aluminium in plasma. In addition to transferrin, aluminium was shown to be associated with citrate in serum, resulting in a low-molecular weight complex. It is postulated that citrate acts as a chelator for aluminium, and that the Al/citrate complex in serum may play an important role in intracellular accumulation, and hence the toxicity, of aluminium. PMID- 2230665 TI - Synthesis and characterization of a new substrate of Photinus pyralis luciferase: 4-methyl-D-luciferin. AB - A derivative of luciferin, 4-methyl-D-luciferin, was synthesized in low yield, and characterized by its ultraviolet and fluorescence spectra. The spectra of luciferin and its derivative are very similar. 4-Methyl-D-luciferin is a substrate of Photinus pyralis luciferase, and it causes light emission in luminometric assays. PMID- 2230666 TI - Spiroadamantane dioxetane substrates--stable labels for luminescence-enhanced enzyme immunoassays. AB - This short communication describes the use of spiroadamantane-1,2 dioxetane substrates for alkaline phosphatase and beta-D-galactosidase in the development of luminescence-enhanced enzyme immunoassays. Until the present work, only peroxidase-luminol/peroxidase systems had been used in such assays. The light reaction kinetics were studied from the time of initiation of the light reaction up to 2 days later. The methods is illustrated by the determination of myeloperoxidase, based on microtitre plate technology, coupled with a microtitre plate luminometer which needs no injector. The alkaline phosphatase and peroxidase systems were compared. PMID- 2230668 TI - Pseudohyperkalaemia in thrombocythaemia. AB - Pseudohyperkalaemia in thrombocythaemia, in its primary form or associated with polycythaemia vera, can occur with platelet counts in excess of 600 X 10(9)/l, and it is not related to high leukocyte or thrombocyte counts. An increment of 0.15 mmol/l serum potassium was found for every 100 X 10(9)/l rise in platelet count with a correlation coefficient of 0.82. Potassium from platelets is not released during the aggregation phase but during the degranulation phase of the coagulation process. PMID- 2230667 TI - Diagnostic utility of a new monoclonal antibody pancreatic isoamylase assay in chronic pancreatic diseases. AB - In order to evaluate the efficacy of a monoclonal pancreatic (P) isoamylase assay in the diagnosis of chronic pancreatic disease and to compare the behavior of this test with that of amylase and elastase 1, these three enzymes were measured in the sera of 39 healthy controls, 28 patients with pancreatic cancer, 50 with chronic pancreatitis and 60 with extra-pancreatic diseases. In patients with chronic relapsing pancreatitis, increased P-isoamylase and elastase 1 values were found in similar percentages (about 70%), whereas the percentage for elevated amylase values was lower (52%). Elastase 1 was increased in 52% of patients with pancreatic cancer, while the other two enzymes were only occasionally elevated. The levels for all three enzymes were abnormal in some patients with extra pancreatic diseases. It may be concluded that this assay for P-isoamylase determination is sufficiently sensitive and reliable in detecting pancreatic inflammation, even though some limitations concerning its specificity should be born in mind. PMID- 2230669 TI - Determination of plasma alpha-amylase in the dog: a test of the specificity of new methods. AB - Commercially available chromogenic substrates for the assay of alpha-amylase were tested for specificity in dog plasma. Blocked alpha-4-nitrophenylmaltoheptaoside and non-blocked beta-4-nitrophenylmaltoheptaoside showed no interference with glucoamylase and were suitable for the measurement of alpha-amylase in dog plasma. In contrast, an alpha-4-nitrophenylmaltoheptaoside showed interference, and was therefore an inappropriate substrate. Reference values with the blocked substrate in a group of 82 non-selected 3 month- to 10 year-old male and female dogs were 355 +/- 131 U/l (mean +/- standard deviation) at 30 degrees C. PMID- 2230670 TI - Measurement of serum alcohol dehydrogenase activity at different pH-values during the course of viral hepatitis in children. AB - Serum alcohol dehydrogenase activity was estimated at pH 10.4 (optimum for the typical liver isoenzyme), 8.8 (optimum for atypical liver isoenzyme), at the physiological serum pH of 7.4, and at pH 9.2, with a view to obtaining the greatest possible difference between patients and controls. Measurements were performed on the sera of 39 children aged from 2 to 13 years, using the Technicon analyzer RA-1000 with the continuously measuring method of Bonnichsen & Brink. Blood sera were tested at the onset of viral hepatitis, in the first week of hospitalization, and three times thereafter at intervals of 7 to 9 days. During the illness, the activity of serum alcohol dehydrogenase, measured at different pH-values, was higher than that of controls. The ratio of activity at pH 10.4 to activity at pH 8.8 in the sera differed from that previously reported for liver cells. The highest increase in alcohol dehydrogenase activity was at pH 9.2. The diagnostic sensitivity of alcohol dehydrogenase determination at this pH is lower than that of alanine aminotransferase, gamma-glutamyltransferase and aspartate amino-transferase, but higher than that of lactate dehydrogenase, alkaline phosphatase and bilirubin; alcohol dehydrogenase activity also shows the best correlation with the activity of gamma-glutamyltransferase. PMID- 2230671 TI - Comparison of methods for neonatal bilirubin. PMID- 2230672 TI - Effects of patient education. PMID- 2230673 TI - Obstetric-enhanced family practice residency training. PMID- 2230674 TI - Implementation of a systematic health maintenance protocol in a private practice. AB - The impact of a policy to introduce a simple health maintenance protocol systematically to all patients belonging to a private practice is reported. Results after 18 months' experience in over 1400 patients indicate that (1) physician compliance was excellent (97% of eligible patients were included, and physician time taken to introduce the protocol at the index visit took less than 4 minutes), and (2) patient acceptance (which varied from procedure to procedure) was good to excellent (minimum acceptance: 77% for sigmoidoscopy; maximum acceptance: 97% for cholesterol screening). For patients seen once, acceptance rates for procedures were generally comparable to prior published performance rates for highly selected patient populations. Integration of a simple health maintenance protocol into routine office care of unselected primary care patients was feasible, effective, and acceptable to patients. Patient refusal was a minor barrier to performance of health maintenance. PMID- 2230675 TI - Screening diabetic patients for microalbuminuria. AB - Abnormal rates of urinary albumin excretion have been shown to predict the development of nephropathy and may signal atherosclerotic disease in diabetic patients. This study demonstrated the feasibility of measuring microalbuminuria in diabetic patients from a large family practice population. Although only one half of the 473 diabetic patients offered free screening took advantage of the testing, those participating did not differ in terms of sex, race, type of diabetes, mean age, systolic blood pressure, and fasting blood glucose levels from those not electing to participate. Over 40% of those screened had abnormally elevated albumin excretion rates as defined as greater than 0.02 g of albumin per gram of creatinine. Those participating in the screening perceived the process as useful and were able to comply with directions for overnight urine collection. Results show that screening for microalbuminuria in diabetic patients cared for by family physicians is feasible, simple, and inexpensive. Interventions to slow or reverse the progression of abnormal microalbuminuria and future risk for nephropathy in those with diabetes are underway. PMID- 2230676 TI - Adult immunization in a network of family practice residency programs. AB - A substantial proportion of morbidity and mortality associated with vaccine preventable diseases occurs among adults. Teaching residents about disease prevention is mandated in the curriculum guidelines for family practice programs. A cooperative study among the Kansas City family practice residency programs was begun to look at immunization behaviors in these teaching programs. A retrospective audit of medical records and a prospective survey of residents and faculty were performed. From the medical records of 400 patients seen for health maintenance examinations, the frequency of tetanus-diphtheria immunizations recorded was 4.75%. The pooled immunization rate recorded for pneumococcal vaccine was 25%, and for influenza vaccine, 24%. Although 93% of respondents knew patients need tetanus-diphtheria immunization every 10 years, on a written questionnaire giving clinical examples, they were less likely to elect to immunize older patients eligible for tetanus-diphtheria vaccine. The following immunization criteria were listed by respondents: for pneumococcal vaccine, age over 65 years (86%); for influenza vaccine, age over 65 years (85%), chronic diseases (69%), residence in a chronic care facility (7%), and being a health care worker (28%). Educational interventions stressing the appropriate criteria and involvement of the patient are planned at the separate programs. PMID- 2230677 TI - The gap between patient reading comprehension and the readability of patient education materials. AB - Patient education materials and hospital forms are given to patients with little regard for their ability to read them. Nationwide sampling and data from the 1980 census suggest that a high proportion of patients cared for in public hospitals are functionally illiterate. In this study, 151 adult primary care patients in five different ambulatory care settings were tested for reading comprehension. Patient education materials and forms from each clinic were analyzed for readability using a standard computer program. A large discrepancy was found between the average patient reading comprehension and the ability levels needed to read patient education materials. The average reading comprehension of public clinic patients was 6th grade 5th month. Most tested patient education materials required a reading level of 11th to 14th grade, and standard institutional consent forms required a college-level reading comprehension. In the public clinics there was a gap of more than 5 years between patient reading levels and the comprehension levels required by written patient materials. PMID- 2230678 TI - A comparison of morbidity and mortality for family physicians' and internists' admissions. AB - The quality of medical care delivered by physicians of different specialties has been the subject of debate for some time. Studies have suffered from a variety of flaws. This study used the MedisGroups comparative database to compare outcome measures in hospitalized patients aged 65 years and older treated either by the family physicians or internists as attending physicians. Using the 10 most common diagnostic related groups for internal medicine, 10,353 admissions to internists were compared with 5,473 admissions to family physicians. Patients admitted by family physicians had a significantly higher admission illness severity and were significantly older. There was no significant difference in morbidity and mortality. The lower average charges for patients admitted to family physicians were statistically significant. PMID- 2230679 TI - Group A beta-hemolytic streptococcal toxic shock from a mild pharyngitis. PMID- 2230680 TI - The match test revisited. Blowing out a candle as a screening test for airflow obstruction. PMID- 2230681 TI - Field performance of the Intoxilyzer 5000: a comparison of blood- and breath alcohol results in Wisconsin drivers. AB - Intoxilyzer 5000 and blood-alcohol results from drivers arrested for operating a motor vehicle while intoxicated and for related offenses were compared during a two-year period. Three hundred and ninety-five pairs of results were studied. The breath- and blood-alcohol specimens in this study were collected within 1 h of each other. The mean blood-alcohol concentration obtained was 0.180 g/dL, with a range from zero to 0.338 g/dL. By comparison, the mean Intoxilyzer 5000 result was 0.16 g/210 L with a range from zero to 0.32 g/210 L. Compared with the blood alcohol result, Intoxilyzer 5000 results were lower by more than 0.01 g/210 L 67% of the time, within 0.01 g/210 L 31% of the time, and higher by more than 0.01 g/210 L 2% of the time. PMID- 2230682 TI - Determination of human immunodeficiency virus antibody status in forensic autopsy cases in Vancouver using a recombinant immunoblot assay. AB - Sera from 207 forensic autopsy cases were tested for the presence of antibody to the human immunodeficiency virus (HIV) using a recombinant immunoblot assay (RIBA) technique developed by Chiron Corporation of Emeryville, California--the Chiron RIBA-HIV216 test system. Out of these cases, 172 autopsies were of individuals with no known risk factors for HIV infection, and of these, 169 had no detectable antibodies to HIV. In 2 cases, the serum reacted with p24 alone on the RIBA-HIV216 assay, but these results were not confirmed by further testing and are considered to be false positive reactions. In 1 case, the serum reacted only with gp41 on the RIBA-HIV216 test but was nonreactive with further testing. This result has been designated equivocal. Of the 35 cases at high risk of HIV infection, 4 had antibodies to HIV detected in postmortem serum samples. The sensitivity (100%) and specificity (98.5%) of the RIBA-HIV216 test system are high. However, the test appears to be more suitable for routine diagnosis of HIV infection than for rapid screening in the mortuary. PMID- 2230683 TI - Cardiac pathology in 470 consecutive forensic autopsies. AB - Cardiovascular disease continues to be the single most common generic cause of sudden and unexpected deaths. Atherosclerotic coronary heart disease and acute myocardial infarction are the most prevalent forms of fatal cardiac disease observed at autopsy. Other cardiac lesions are frequently listed as causes of death, but the prevalence of such lesions as incidental findings in the general population is unknown. In this study, 470 consecutive forensic autopsies were evaluated for minor and major anomalies. The most frequently observed major congenital finding was floppy mitral valve (5%). Tunneled coronary arteries, considered minor congenital findings, were seen in 29%. Atherosclerotic coronary heart disease was the most common major acquired finding, observed in 16% of cases. Of the 470 hearts, only 8% were considered normal. PMID- 2230684 TI - Survey of gunshot residue analysis in forensic science laboratories. AB - The purpose of this survey was to determine the methods of analysis being used on gunshot residue (GSR) samples in forensic science laboratories across the United States. In addition, the two general techniques of GSR analysis are compared and contrasted. Problems encountered by analysts using scanning electron microscopy/energy-dispersive X-ray analysis (SEM/EDX) are discussed. PMID- 2230685 TI - Barium and antimony distributions on the hands of nonshooters. AB - Barium and antimony levels from selected areas of the left and right hands of 269 nonshooters provide a database for interpretation of gunshot residue swab analysis results. The database represents a variety of activities of individuals sampled by collectors throughout the United States. Nonshooting exposure to barium and antimony can generally be distinguished from firearms-associated exposure by considering the relative levels of the elements, location on the hands, and condition of the swabs. Consistent definition of sampling procedures and accurate analytical results make this database applicable for interpretation of data generated by most gunshot residue swab examiners. PMID- 2230686 TI - The rapid determination of the ABO group from body fluids (or stains) by dot enzyme-linked immunosorbent assay (dot-ELISA) using enzyme-labeled monoclonal antibodies. AB - Using ABH enzyme-labeled monoclonal antibodies, the authors could rapidly detect the ABO group from body fluids and body fluid stains by the dot enzyme-linked immunosorbent assay (dot-ELISA). In this test, the antigen was immobilized on nitrocellulose paper; the entire piece of paper was coated with an appropriate dilution of enzyme-labeled McAb directly against the antigen of interest; and, finally, 3,3'-diaminobenzidine (DAB) substrate solution was added. The site of a positive reaction is clearly visible as a brown spot. We analyzed 521 samples and got satisfactory results. We also analyzed 99 practical case samples by this method and achieved the same results as those obtained by other researchers using other methods. This method is accurate, simple, direct, rapid, and sensitive; it also produces easily observed results, requires no equipment, and can be completed in 30 min. The test proved to be clearly more sensitive for the detection of the ABO blood group in secretor saliva than the conventional hemagglutination inhibition test. Also saliva diluted 10(-4) to 10(-5) and the ABO group of nonsecretor saliva and urine could be easily detected by this method. PMID- 2230687 TI - Concentration of urine samples by three different procedures: ABO typing from concentrated urine samples. AB - Urine samples from 28 donors with known blood group and secretor status were concentrated by three different procedures, and ABO typing on the concentrated samples was successfully performed after 12 weeks of storage. The effects of storage with or without sodium azide on ABO typing and on the pH values at several different temperatures were also studied. PMID- 2230688 TI - Fatal ethanol intoxication from household products not intended for ingestion. AB - Fatal acute ethanol intoxication is frequently encountered in medicolegal practice. Although the vast majority of acute ethanol toxicity deaths follow the ingestion of conventional alcoholic beverages, ethanol can be obtained from a variety of commercial products, which often contain high levels of ethyl alcohol but are not manufactured or designed for consumption. Such products may be easily purchased in locales where statutory limitations restrict liquor availability on Sundays or during the early morning hours. Several acute ethanol fatalities have been encountered in New Mexico that were directly related to consumption of non beverage ethanol-containing products, all of them occurring during times when alcoholic beverage sales were restricted. Despite the fact that manufacturers deliberately include compounds in these products that discourage ingestion, this policy apparently does little to deter individuals who are searching for a source of ethanol when no conventional beverages are available. The products that were consumed in these fatalities also contained other compounds which would be toxic at much greater concentrations, but which were inconsequential in their effects in comparison with the direct toxic effect of ethanol. Investigation of the scene and awareness that alcohol-containing products can be fatally abused are essential to detecting these unconventional ethanol sources. PMID- 2230689 TI - Causes of death in hospitalized intravenous drug abusers. AB - The authors reviewed at autopsy the causes of death of 274 patients with evidence of intravenous drug abuse who had been admitted to a large public hospital. There were 127 who died from diseases unrelated to intravenous drug abuse, and in 41% of these, chronic alcoholism was implicated. Deaths from overdose syndromes and drug-related organ pathology comprised only 11% of all cases. The mean age at death was 39 years. There was a male/female ratio of 3.6:1. Half of all patients died from infection--72 from acquired immunodeficiency syndrome (AIDS) alone. These findings indicate that persons hospitalized with a history of intravenous drug abuse usually die from causes other than overdose and that AIDS and chronic alcoholism are significant problems. Emphasis should be placed upon detecting "hidden" intravenous drug deaths to provide more accurate statistical information. PMID- 2230690 TI - The grief process in those admitted to regional secure units following homicide. AB - Although there is considerable literature on grief and grief work, there have been few studies of the grief process in those who have killed someone. This paper reviews the scope of this problem in England and Wales and examines a number of issues in connection with the grieving process in those who have killed but, because they were found to be suffering from an "abnormality of mind" at the time of the offence, were found not guilty of murder. Increasingly, these patients are referred for treatment to Regional Secure Units, under hospital orders of the Mental Health Act of 1983. PMID- 2230691 TI - Liberty and tardive dyskinesia: informed consent to antipsychotic medication in the forensic psychiatric hospital. AB - This paper addresses informed consent to antipsychotic medication of those incarcerated in a forensic psychiatric hospital. The ways in which the unique setting of the forensic psychiatric hospital impinge upon the three components of informed consent--information, voluntariness, and competency--are explored. Special attention is given to the risk-benefit ratio of receiving antipsychotic medication in terms of the liberty interests at stake--freedom of movement, that is, the effects of tardive dyskinesia, and freedom of space, that is, release from the forensic psychiatric facility. PMID- 2230692 TI - Orosomucoid 1 phenotyping from human urine by isoelectric focusing. AB - Orosomucoid 1 polymorphism was revealed in human urine by isoelectric focusing and immunoprinting on polyacrylamide gels. The orosomucoid in urine samples was recovered and concentrated by using immobilized allo A lectin. The orosomucoid 1 phenotypes of 60 urine samples correlated with those of the corresponding serum samples. PMID- 2230693 TI - Amplification of a variable number of tandem repeats (VNTR) locus (pMCT118) by the polymerase chain reaction (PCR) and its application to forensic science. AB - A genetic locus (D1S58, defined by DNA probe pMCT118) that contains a variable number of tandem repeats (VNTR) has been successfully amplified from a very small amount of genomic deoxyribonucleic acid (DNA) by the polymerase chain reaction (PCR). The DNA sequence of the locus was determined and was found to consist of a 16-base consensus sequence and flanking sequences. Oligonucleotide primers complementary to the flanking sequences were synthesized to serve as primers for amplification of MCT118 by the PCR method. Human genomic DNA isolated from blood (2 ng from each sample) was successfully amplified at the MCT118 locus, and polymorphic bands were detectable by ethidium bromide staining after electrophoresis on polyacrylamide gels. Determination of genotypes at this VNTR locus can now be routinely achieved within 24 h, without the need for Southern blots or radioactive materials. Furthermore, the small size (387 to 723 base pairs) of the DNA fragments produced in the PCR amplification permits good resolution of individual alleles that differ by only one repeat unit. The precise specification of the number of tandem repeats present in each allelic fragment is reproducible from one analysis to another. PMID- 2230694 TI - Distributions of genetic markers in a Nebraska population. AB - Seven genetic marker systems were analyzed from liquid blood and dried bloodstain specimens submitted to the Nebraska State Patrol Crime Laboratory from various law enforcement agencies throughout Nebraska. The phenotypic and genotypic frequencies for the ABO, Lewis, esterase D (ESD), phosphoglucomutase (PGM), adenylate kinase (AK), adenosine deaminase (ADA), and haptoglobin (HP) systems were calculated. The results indicate that the phenotypic frequencies are generally in agreement with frequencies reported in other populations in the United States. PMID- 2230695 TI - Inadvertent clavicular fractures caused by "chiropractic" manipulations in an infant: an unusual form of pseudoabuse. AB - A nine-month-old child was found unresponsive in his crib, five hours after his last feeding. At autopsy, there were no external or internal signs of abuse or neglect, and a few visceral pleural and epicardial petechiae were consistent with the sudden infant death syndrome (SIDS). However, postmortem total body radiographs revealed healing, symmetrical clavicular fractures and a healing left medial humeral epicondyle fracture. The parents had no explanation for these injuries and denied causing any harm to the child. The location and nature of the fractures strongly suggested abusive origin, and the case was reported to the police and the district attorney's office as child abuse. During the investigation, information from the parents indicated that the child had undergone "chiropractic" manipulations by an unlicensed therapist, between three and four weeks prior to death, to correct supposed "shoulder dislocations." This time interval correlated with the histologic age of the injuries, and the history explained their unusual bilateral location and appearance. The parents were exonerated of abuse charges, and the death was ascribed to SIDS. PMID- 2230696 TI - An elliptical incised wound of the breast misinterpreted as a bite injury. AB - Bite injuries upon homicide victims are most often initially identified by the forensic pathologist during the course of the autopsy examination. Following such recognition, the injury or photographs of the traumatized site are then referred to a forensic odontologist for his or her examination, further characterization, and subsequent comparison with any suspect's dentition. However, if the pathologist misidentifies an injury caused by another mechanism as a human bite, this mistake can potentially be perpetuated by the dental consultant, since relatively few dentists regularly examine traumatic injuries other than those arising from bites. To illustrate such an event, a case is presented involving an incised wound of the breast, which was originally identified as an avulsive bite wound. Detailed examination by two odontologic consultants confirmed the wound as having been caused by human teeth, and further, they related the "bite injury" to a specific individual. The bite injury interpretation represented the only scientific evidence implicating the suspect at a subsequent trial for capital murder. Later examination of the tissues and photographs by a forensic pathologist and another dental consultant revealed that the injury was not due to human dentition, but rather resulted from a sharp-edged instrument. These consultants conducted a unique experiment to reduplicate the injury and prove its causation. This information was presented to the jury during the suspect's trial and resulted in his acquittal on all charges. PMID- 2230697 TI - Multiple gunshot wounds of the head: an anthropological view. AB - A decomposed body was judged at the scene to have two gunshot wounds of the thorax and three of the head. Confirmed at autopsy, the condition of the remains precluded conclusions about the precise nature of the defects. Preparation and reconstruction of the skull disclosed seven large cranial defects and a series of fractures. This preparation allowed the application of well-known principles of gunshot wound analysis. Although the analysis of specific gunshot wound defects is well covered in the literature, there are few examples of the application of gunshot wound principles to complex wound cases. Three entrances and three exits were identified. A seventh defect resulted from bullet passage. Finally, the wounds were sequenced. PMID- 2230698 TI - Home health care. Another emerging Mr. Hyde? PMID- 2230699 TI - Lest we forget. PMID- 2230700 TI - James G. Lyerly remembered. PMID- 2230701 TI - PRO reviewers needed. PMID- 2230702 TI - Testing for HIV infection. PMID- 2230703 TI - Relationship between Type A personality and coronary heart disease. Analysis of five cohort studies. AB - Five prospective cohort studies were compared in order to evaluate the relationship between type A personality (aggressive behavior) and coronary heart disease (CHD). The Western Collaborative Group Study (WCGS) demonstrated increased risk for CHD in males with type A personality. A follow-up study revealed a greater incidence of second myocardial infarction. The Framingham study showed higher rates of CHD in type A men and women. Two studies, MRFIT and a third evaluation of the WCGS, revealed no relationship between type A personality and CHD and mortality due to CHD. Because the studies disagree in the relationship between type A personality and CHD, it is impossible to conclude that type A personality is a risk for CHD. PMID- 2230704 TI - Results of emergent versus elective cardiac transplantation procedures. AB - Twenty-six patients underwent emergent (Group I) and 34 patients elective (Group II) cardiac transplantation (C. Tx.) from June 1985 through June 1989. Age, sex, etiology, presence of diabetes, renal failure and pulmonary artery pressures were comparable for both groups (P greater than 0.5). Twenty-two patients were in New York Heart Association (NYHA) Class IV for Group I and 17 for Group II. Group I included 12 patients on inotropic agents, five on intra-aortic balloon pump (IABP) and one on IABP and cardiopulmonary bypass (CPB). Elective patients were stable at home. Location of the donor heart and mean ischemic times were comparable for both groups. Early mortality (within 30 days) included four patients for Group I and two for Group II. There were four late deaths for Group I patients and six for Group II. Four deaths were due to infection, six to rejection, two to malignancy, two neurological and one each to suicide and multisystem failure. Immunosuppression regimen was similar for both groups. The number and severity of early and late rejection episodes were similar despite blood group crossing in 11 patients for Group I (P less than .01). Incidence of infection was comparable. Favorable lifestyles were comparable, including employment of 12 patients for Group I and 16 for Group II. Cumulative survival for the entire series was 70% at two years. The study indicates that the results of emergent and elective cardiac transplantation procedures are equally gratifying, that mortality is mainly related to rejection and sepsis complications and blood group crossing does not significantly increase the number of rejection episodes. PMID- 2230705 TI - Unusual cases of perforated diverticulitis of colon. AB - Two extraordinary cases of perforated diverticulitis with extraperitoneal presentation are described. The diagnosis should be kept in mind in unusual cases of pain or sepsis in the elderly. A brief review of pathogenesis is given. Surgical treatment with primary resection and drainage is emphasized. PMID- 2230706 TI - R.C. Philips Research and Education Unit. PMID- 2230707 TI - Ophthalmic surgical management of facial paralysis. AB - Combinations of these procedures have been performed on more than 50 patients to date, with the longest follow-up being greater than 8 years. All of these patients presented with complaints of ocular irritation, tearing, photophobia, and impaired vision. Several had severe epithelial keratopathy. Some patients have also been treated following neurosurgical procedures which caused paralysis of the fifth and seventh cranial nerves, resulting in both corneal anesthesia and facial paralysis. Patients have done very well after these procedures and have achieved ocular comfort, reduced tearing, and corneal protection without the need for disfiguring and visually occluding tarsorrhaphies or other procedures. In some instances, they may still require artificial tears during the day or a lubricating protective ointment for the eye at bedtime. There have been no significant complications in this series; no cases of gold weight extrusion, recurrent ectropion, or persistent corneal epithelial keratopathy. Some patients have complained of continued excessive tearing which is most likely due to paralysis of the lacrimal pump, resulting in ineffective tear drainage to the nasal lacrimal duct. However, these patients have still noted markedly reduced tearing compared to their preoperative condition. One patient underwent secondary release of her medial canthoplasty following return of facial nerve function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230708 TI - Absorbance signals from resting frog skeletal muscle fibers injected with the pH indicator dye, phenol red. AB - Singly dissected twitch fibers from frog muscle were studied on an optical bench apparatus after micro-injection with the pH indicator dye, phenol red. Dye related absorbances in myoplasm, denoted by A0(lambda) and A90(lambda), were estimated as a function of wavelength lambda (450 nm less than or equal to lambda less than or equal to 640 nm) with light polarized parallel (0 degrees) and perpendicular (90 degrees) to the fiber axis respectively. At all lambda, A0(lambda) was slightly greater than A90(lambda), indicating that some of the phenol red molecules were bound to oriented structures accessible to myoplasm. The phenol red "isotropic" signal, [A0(lambda) + 2A90(lambda)]/3, a quantity equal to the average absorbance of all the dye molecules independent of their orientation, had a spectral shape that was red-shifted by approximately 10 nm in comparison with in vitro dye calibration curves measured in 140 mM KCl. The red shifted spectrum also indicates that some phenol red molecules were bound in myoplasm. A quantitative estimate of indicator binding was obtained from measurements of the dye's apparent diffusion constant in myoplasm, denoted by Dapp. The small value of Dapp, 0.37 x 10(-6) cm2 s-1 (at 16 degrees C), can be explained if approximately 80% of the dye was bound to myoplasmic sites of low mobility. To estimate the apparent myoplasmic pH, denoted by pHapp, the isotropic absorbance of phenol red was fitted by in vitro calibration spectra. pHapp was found to be independent of dye concentration (0.2-2 mM), but varied widely (range, 6.8-7.5; mean value, 7.17) among fibers judged from functional characteristics to be normal. When fibers were subjected to acid or alkaline loads by exposure to Ringer's solution containing, respectively, dissolved CO2 or NH3, the changes in pHapp were in agreement with those expected from pH micro electrode studies. It is concluded that in spite of the several indications for the presence of bound phenol red inside muscle cells, the pHapp signal from the indicator is useful for monitoring changes in myoplasmic pH in response to physiological and pharmacological manipulations. PMID- 2230709 TI - Changes in phenol red absorbance in response to electrical stimulation of frog skeletal muscle fibers. AB - Intact single twitch fibers from frog muscle were stretched to long sarcomere length, micro-injected with the pH indicator dye phenol red, and activated by action potential stimulation. Indicator-related absorbance changes (denoted by delta A0 and delta A90) were measured with 0 degree and 90 degrees polarized light (oriented, respectively, parallel and perpendicular to the fiber axis). Two components of delta A were detected that had generally similar time courses. The "isotropic" component, calculated as the weighted average (delta A0 + 2 delta A90)/3, had the wavelength dependence expected for a change in myoplasmic pH. If calibrated in pH units, this signal's peak amplitude, which occurred 15-20 ms after stimulation, corresponded to a myoplasmic alkalization of average value 0.0025 +/- 0.0002 (+/- SEM; n = 9). The time course of this change, as judged from a comparison with that of the fibers' intrinsic birefringence signal, was delayed slightly with respect to that of the myoplasmic free [Ca2+] transient. On average, the times to half-peak and peak of the phenol red isotropic signal lagged those of the birefringence signal by 2.4 +/- 0.2 ms (+/- SEM; n = 8) and 8.4 +/- 0.5 ms (+/- SEM; n = 4), respectively. The other component of the phenol red signal was "dichroic," i.e., detected as a difference (delta A0-delta A90 greater than 0) between the two polarized absorbance changes. The wavelength dependence of this signal was similar to that of the phenol red resting dichroic signal (Baylor and Hollingworth. 1990. J. Gen. Physiol. 96:449-471). Because of the presence of the active dichroic signal, and because approximately 80% of the phenol red molecules appear to be bound in the resting state to either soluble or structural sites, the possibility exists that myoplasmic events other than a change in pH underlie the phenol red isotropic signal. PMID- 2230710 TI - Perturbation of sarcoplasmic reticulum calcium release and phenol red absorbance transients by large concentrations of fura-2 injected into frog skeletal muscle fibers. AB - Intact single twitch fibers from frog muscle were studied on an optical bench apparatus after micro-injection with two indicator dyes: phenol red, to monitor a previously described signal (denoted delta pHapp; Hollingworth and Baylor. 1990. J. Gen. Physiol. 96:473-491) possibly reflective of a myoplasmic pH change following action potential stimulation; and fura-2, to monitor the associated change in the myoplasmic free calcium concentration (delta[Ca2+]). Additionally, it was expected that large myoplasmic concentrations of fura-2 (0.5-1.5 mM) might alter delta pHapp, since it was previously found (Baylor and Hollingworth. 1988. J. Physiol. 403:151-192) that the Ca2(+)-buffering effects of large fura-2 concentrations: (a) increase the estimated total concentration of Ca2+ (denoted by delta[CaT]) released from the sarcoplasmic reticulum (SR), but (b) reduce and abbreviate delta[Ca2+]. The experiments show that delta pHapp was increased at the larger fura-2 concentrations; moreover, the increase in delta pHapp was approximately in proportion to the increase in delta[CaT]. At all fura-2 concentrations, the time course of delta pHapp, through time to peak, was closely similar to, although probably slightly slower than, that of delta[CaT]. These properties of delta pHapp are consistent with an hypothesis proposed by Meissner and Young (1980. J. Biol. Chem. 255:6814-6819) and Somlyo et al. (1981. J. Cell Biol. 90:577-594) that a proton flux from the myoplasm into the SR supplies a portion of the electrical charge balance required as Ca2+ is released from the SR into the myoplasm. A comparison of the amplitude of delta pHapp with that of delta[CaT] indicates that, in response to a single action potential, 10-15% of the charge balance required for Ca2+ release may be carried by protons. PMID- 2230711 TI - Voltage-dependent block of charge movement components by nifedipine in frog skeletal muscle. AB - Potential-dependent inhibition of charge movement components by nifedipine was studied in intact, voltage-clamped, frog skeletal muscle fibers. Available charge was reduced by small shifts in holding potential (from -100 mV to -70 mV) in 2 microM nifedipine, without changes in the capacitance deduced from control (-120 mV to -100 mV) voltage steps made at a fully polarized (-100 mV) holding potential. These voltage-dependent effects did not occur in lower (0-0.5 microM) nifedipine concentrations. The voltage dependence of membrane capacitance at higher (10 microM) nifedipine concentrations was reduced even in fully polarized fibers, but shifting the holding voltage produced no further block. Voltage dependent inhibition by nifedipine was associated with a fall in available charge, and a reduction in the charge and capacitance-voltage relationships and of late (q gamma) charging transients. It thus separated a membrane-capacitance with a distinct and steep steady-state voltage dependence. Tetracaine (2 mM) reduced voltage-dependent membrane capacitance and nonlinear charge more than did nifedipine. However, nifedipine did not exert voltage-dependent effects on charging currents, membrane capacitance, or inactivation of tetracaine-resistant (q beta) charge. This excludes participation of q beta, or the membrane charge as a whole, from the voltage-dependent effects of nifedipine. Rather, the findings suggest that the charge susceptible to potential-dependent block by nifedipine falls within the tetracaine-sensitive (q gamma) category of intramembrane charge. PMID- 2230712 TI - Circadian rhythms in Limulus photoreceptors. II. Quantum bumps. AB - The light response of the lateral eye of the horseshoe crab, Limulus polyphemus, increases at night, while the frequency of spontaneous discrete fluctuations of its photoreceptor membrane potential (quantum bumps) decreases. These changes are controlled by a circadian clock in the brain, which transmits activity to the eye via efferent optic nerve fibers (Barlow, R. B., S. J. Bolanski, and M. L Brachman. 1977. Science. 197:86-89). Here we report the results of experiments in which we recorded from single Limulus photoreceptors in vivo for several days and studied in detail changes in their physiological and membrane properties. We found that: (a) The shape of (voltage) quantum bumps changes with the time of day. At night, spontaneous bumps and bumps evoked by dim light are prolonged. The return of the membrane potential to its resting level is delayed, but the rise time of the bump is unaffected. On average, the area under a bump is 2.4 times greater at night than during the day. (b) The rate of spontaneous bumps decreases at night by roughly a factor of 3, but their amplitude distribution remains unchanged. (c) The resting potential and resistance of the photoreceptor membrane do not change with the time of day. (d) the relationship between injected current and impulse rate of the second order neuron, the eccentric cell, also remains unchanged with the time of day. Thus the efferent input from the brain to the retina modulates some of the membrane properties of photoreceptor cells. Our findings suggest that the efferent input acts on ionic channels in the membrane to increase the sensitivity of the photoreceptor to light. PMID- 2230713 TI - An effective technique for enrichment and isolation of Candida cloacae mutants defective in alkane catabolism. AB - Techniques are described which allow mutated populations of Candida cloacae to be enriched efficiently (up to 167-fold in one round of enrichment) for mutants deficient in the alkane degradation pathway (Alk-). Such mutants, as well as being of scientific importance in studies of the degradation pathway, are also of commercial interest because several of the degradative intermediates are of value to the chemical industry. The Alk- mutants were readily isolated by their inability to grow on agar plates supplied with hexadecane as sole carbon source. A total of 288 Alk- mutants were isolated from, effectively, 4 x 10(6) mutagen treated cells. They were further characterized by replica-plating using palmitic acid (PA) or acetate (Ac) as sole carbon source. Preliminary screening studies showed that of the 84 Alk- PA- Ac+ mutants, most could accumulate dicarboxylic acids from hexadecane and palmitic acid and at least one mutant also produced 3 hydroxyhexadecanedioic acid. Of the 80 mutants characterized as Alk- PA+, 16 produced small amounts of hexadecanol. PMID- 2230714 TI - Urogenital, maternal and neonatal isolates of Haemophilus influenzae: identification of unusually virulent serologically non-typable clone families and evidence for a new Haemophilus species. AB - A collection of 117 strains of Haemophilus influenzae, including 112 non-typable isolates recovered predominantly in the USA and France from genital, obstetric and neonatal sources, was characterized by the electrophoretic mobilities of 10 metabolic enzymes. Eighty-six distinctive multilocus chromosomal genotypes (electrophoretic types, ETs) were distinguished on the basis of allele profiles at the enzyme loci. Isolates of five allied biotype IV ETs were highly divergent from all other strains and hybridization of chromosomal DNA revealed that they undoubtedly represent a previously unrecognized species of Haemophilus. Isolates representing these ETs were recovered predominantly from obstetric infections and serious neonatal diseases and apparently possess specific tropism for the genital tract. Strains of these five ETs were present in samples from both the USA and France, but only in the USA did they cause bacteraemia and meningitis, an occurrence which probably reflects differences in patient management between the two countries. Although strains assigned to H. influenzae (sensu stricto) were strongly polymorphic in multilocus enzyme genotype, 69% of isolates recovered from patients with meningitis and/or septicaemia were assigned to only two clone families, a result suggesting that some serologically nontypable strains of H. influenzae originating from the genital tract are unusually virulent. PMID- 2230715 TI - Effect of ethanol on the phospholipid and fatty acid content of Schizosaccharomyces pombe membranes. AB - Ethanol at concentrations up to 5% (v/v) had no effect on the growth of Schizosaccharomyces pombe, whereas concentrations over 7.5% were inhibitory. The major membrane phospholipids in S. pombe cells growing aerobically in the absence of added ethanol were phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine. Oleic acid (18:1) was the main fatty acid. When ethanol (7.5%) was added to aerobically growing cultures, the phosphatidylinositol content increased, whereas the 18:1 content decreased. Similar changes were observed in the membrane phospholipids of cells grown anaerobically without ethanol. However, the presence of ethanol in anaerobically growing cultures had an opposite effect on fatty acids, as the 18:1 content increased. The results support the idea that ethanol tolerance in S. pombe may be connected with a high content of 18:1 fatty acids, and with the ability to maintain a high rate of phospholipid biosynthesis. PMID- 2230716 TI - Acetolysis and 1H NMR studies on mannans isolated from very flocculent and weakly flocculent cells of Pichia pastoris IFP 206. AB - Growth of the yeast Pichia pastoris IFP 206 in methanol- and glucose-containing media led respectively to very and weakly flocculent cells. Mannans from both kinds of cells were extracted and compared. Chemical analysis and molecular mass estimation showed some differences between the mannans from very and weakly flocculent cells, especially in quantitative amino acid content. 1H NMR analysis showed that both kinds of mannan contained alpha-1,2 and beta-1,2 linkages. Two acetolysis conditions, combined with 1H NMR analysis, revealed that mannans from both kinds of cells were composed of mannose, mannobiose, mannotriose, mannotetraose and mannopentaose side-chains with the following respective structures: Man; Man alpha 1---2Man; Man alpha 1----2Man alpha 1----2Man; Man beta 1----2Man alpha 1----2Man; Man beta 1----2Man beta 1----2Man alpha 1--- 2Man; Man alpha 1----2Man beta 1----2Man beta 1----2Man alpha 1----2Man. Additionally the beta-1,2 linkages of the non-reducing terminal residues of the mannotetraose were shown to be acetolysis-labile. The mannans from very flocculent cells were richer in mannopentaose than the mannans from weakly flocculent cells. According to these results, the extended conformations in the branching moieties of the mannan could be the basis of the higher degree of flocculation of the methanol-grown cells. PMID- 2230717 TI - Characterization of a glycerol kinase mutant of Aspergillus niger. AB - A glycerol-kinase-deficient mutant of Aspergillus niger was isolated. Genetic analysis revealed that the mutation is located on linkage group VI. The phenotype of this mutant differed from that of a glycerol kinase mutant of Aspergillus nidulans in its ability to utilize dihydroxyacetone (DHA). The weak growth on glycerol of the A. niger glycerol kinase mutant showed that glycerol phosphorylation is an important step in glycerol catabolism. The mutant could still grow normally on DHA because of the presence of a DHA kinase. This enzyme, probably in combination with an NAD(+)-dependent glycerol dehydrogenase, present only in the mutant, is responsible for the weak growth of the mutant on glycerol. Enzymic analysis of both the mutant and the parental strain showed that at least three different glycerol dehydrogenases were formed under different physiological conditions: the NAD(+)-dependent enzyme described above, a constitutive NADP(+) dependent enzyme and a D-glyceraldehyde-specific enzyme induced on D galacturonate. The glycerol kinase mutant showed impaired growth on D galacturonate. PMID- 2230718 TI - Molecular cloning and nucleotide sequence of a gene for alkaline cellulase from Bacillus sp. KSM-635. AB - A gene for alkaline cellulase from the alkalophilic Bacillus sp. KSM-635 was cloned into the HindIII site of pBR322 and expressed in Escherichia coli HB101. Although the recombinant plasmid contained two HindIII inserts of 2.6 kb and 4.0 kb, the inserts were found to be contiguous in the Bacillus genome by hybridization analysis. Nucleotide sequences of a 2.4 kb region which was indispensable for the production of cellulase, and the flanking, 1.1 kb region, were determined. There was an open reading frame (ORF) of 2823 bp in the 3498 bp sequence determined, which encoded 941 amino acid residues. Two putative ribosome binding sites and a sigma 43-type, promoter-like sequence were found upstream from an initiation codon in the ORF. The deduced amino-terminal sequence resembles the signal peptide of extracellular proteins. A region of amino acids, 249 to 568, of the deduced amino acid sequence of the cellulase from this organism is homologous with those of alkaline and neutral enzymes of other micro organisms, but nine amino acid residues were found to be conserved only in the alkaline enzymes. PMID- 2230719 TI - Molecular cloning and characterization of the spaB gene of Streptococcus sobrinus. AB - A gene of Streptococcus sobrinus 6715 (serotype g) designated spaB and encoding a surface protein antigen was isolated from a cosmid gene bank. A 5.4 kb HindIII/AvaI DNA fragment containing the gene was inserted into plasmid pBR322 to yield plasmid pXI404. Analysis of plasmid-encoded gene products showed that the 5.4 kb fragment of pXI404 encoded a 195 kDa protein. Southern blot experiments revealed that the 5.4 kb chromosomal insert DNA had sequence similarity with genomic DNA of S. sobrinus 6715, S. sobrinus B13 (serotype d) and Streptococcus cricetus HS6 (serotype a). The recombinant SpaB protein (rSpaB) was purified and monospecific antiserum was prepared. With immunological techniques and the anti rSpaB serum, we have shown: (1) that the rSpaB protein has physico-chemical and antigenic identity with the S. sobrinus SpaB protein, (2) the presence of cross reactive proteins in the extracellular protein of serotypes a and d of the mutans group of streptococci and (3) that the SpaB protein is expressed on the surface of mutans streptococcal serotypes a, d and g. PMID- 2230720 TI - Structure of a Rhodococcus gene encoding pigment production in Escherichia coli. AB - A 2.1 kbp DNA fragment from Rhodococcus strain ATCC 21145 gave rise to the production of blue and pink pigments in Escherichia coli when cloned downstream of a strong promoter. The sequence of this DNA fragment contains a single open reading frame with a putative ribosome-binding site, potentially coding for a single protein of Mr 42,560. Deletion analysis and in vitro transcription translation experiments support the hypothesis that pigment production in E. coli is due to a single enzyme whose catalytic activity is still unknown. This small pigment gene may become useful for the development of a new generation of chromogenic cloning vectors which do not require expensive substrates for the detection of gene expression. PMID- 2230721 TI - Further biological and molecular characterization of actinophage VWB. AB - The development cycle of the temperate actinophage VWB was investigated. Adsorption of most phage particles occurred within 30 min and the adsorption constant was 0.6 x 10(-8) ml min-1. The latent and rise periods were 140 and 100 min, respectively, and the burst size was estimated to be 130-250 p.f.u. Although phage VWB could infect only Streptomyces venezuelae ETH 14630 (ATCC 40755), of six different S. venezuelae strains tested, phage DNA could be introduced by transfection into most non-infectible strains. Upon transfection, phage DNA was propagated in these non-infectible strains and phage particles were released. In addition, the transfected strains could be lysogenized. By comparison of restriction fragments of VWB DNA, either free or integrated in the chromosomal DNA of the S. venezuelae ETH 14630 lysogen, the attachment site was localized. PAGE of the phage proteins revealed at least 17 different proteins with three major bands estimated as 16.5, 27.2 and 43 kDa in size. The N-terminal amino acid sequence of these supposed major head and tail proteins was determined. The corresponding DNA sequences on the phage genome were localized using oligonucleotides synthesized on the basis of the N-terminal amino acid sequences. The genes coding for the major structural proteins were shown to be clustered, as has been observed for other bacteriophages. PMID- 2230722 TI - Nutritional stress proteins in Candida albicans. AB - Starving cells of Candida albicans synthesize at least seven proteins that represent nutritional-stress proteins (NSP). Such NSPs are formed by both germination-competent and germination-deficient strains of C. albicans. Heat shock proteins (HSP) are not formed by starving cells. Germination-competent cells synthesize specific sets of proteins when incubated in a starvation medium that contains the germ-tube-inducing substances N-acetyl-D-glucosamine or L proline. Both sets of induced proteins were also synthesized by a germination deficient strain of C. albicans. PMID- 2230723 TI - Cloning and characterization of the gene for the '19 kDa' antigen of Mycobacterium bovis. AB - Monoclonal antibody CMA134.1 reacted with a protein antigen of apparent molecular mass 22 kDa from Mycobacterium bovis and Mycobacterium tuberculosis, and with an apparently 24 kDa antigen of Mycobacterium kansasii, but not with other mycobacteria or related species. This antibody was used to screen a gene library of M. bovis in lambda gt11 and identified a recombinant clone that expressed a protein with an apparent molecular mass of 19-20 kDa. Gene expression occurred from the lac promoter in lambda gt11, but used an unidentified vector promoter, possibly that of the replication primer RNA, in the final plasmid construct. The sequence of an 840 bp fragment was determined and shown to code for a product of 15 kDa. This sequence is identical to that, independently determined, of a gene from M. tuberculosis, usually referred to as the 19 kDa antigen. The reasons for the apparent size discrepancies are discussed. PMID- 2230724 TI - Lactoferrin and transferrin damage of the gram-negative outer membrane is modulated by Ca2+ and Mg2+. AB - Lactoferrin and transferrin have antimicrobial activity against selected Gram negative bacteria, but the mechanism of action has not been defined. We studied the ability of lactoferrin and transferrin to damage the Gram-negative outer membrane. Lipopolysaccharide release by the proteins could be blocked by concurrent addition of Ca2+ and Mg2+. Addition of Ca2+ also blocked the ability of lactoferrin to increase the susceptibility of Escherichia coli to rifampicin. Transferrin, but not lactoferrin, increased susceptibility of Gram-negative bacteria to deoxycholate, with reversal of sensitivity occurring with exposure to Ca2+ or Mg2+. In transmission electron microscopy studies polymyxin B caused finger-like membrane projections, but no morphological alterations were seen in cells exposed to EDTA, lactoferrin or transferrin. These data provide further evidence that lactoferrin and transferrin act as membrane-active agents with the effects modulated by Ca2+ and Mg2+. PMID- 2230725 TI - Expression of cauliflower mosaic virus gene I in insect cells using a novel polyhedrin-based baculovirus expression vector. AB - An improved polyhedrin-based baculovirus expression vector was constructed to expedite distinguishing infections by putative baculovirus recombinants from infections by wild-type (wt) baculovirus. The vector utilizes the Escherichia coli beta-galactosidase gene (lacZ) as a genetic marker for positive recombination between wt Autographa californica nuclear polyhedrosis virus and the baculovirus transfer vector. The marker gene/expression cassette was constructed so that lacZ and the deleted polyhedrin gene were transcribed in opposite orientations, both terminating in a simian virus 40 DNA fragment which acts as a bidirectional terminator. In the constructed vector, lacZ is transcribed from the Drosophila melanogaster heat-shock promoter (hsp 70), which is constitutively expressed in baculovirus-infected Spodoptera frugiperda (Sf) cells, thereby making the site of the deleted polyhedrin gene available for the insertion and expression of foreign genes under the control of the polyhedrin promoter. Recombinant baculoviruses are readily selected in plaque assays by the development of a blue colour upon the addition of X-Gal. The colour selection renders the retrieval of recombinants less dependent on a high frequency of recombination between the transfer vector and wt baculovirus DNA. The usefulness of this new vector was illustrated by expressing gene I of cauliflower mosaic virus, which encodes a protein of Mr 46,000. Expression of gene I was at the same level as in cells infected with a conventional polyhedrin-based expression vector. Gene I protein formed large hollow fibre-like structures in the cytoplasm of infected Sf cells. This is the first plant virus protein to be expressed in insect cells by a recombinant baculovirus. PMID- 2230726 TI - Genomic characterization of phenotypic variants of beet curly top virus. AB - Full-length infectious DNA clones were constructed for four distinct phenotypic variants of beet curly top virus (BCTV). Southern hybridization assays indicated that each cloned BCTV genome shared sequence homology with pBCT-028, a full length infectious DNA clone of a California isolate of BCTV previously characterized by others. Restriction endonuclease maps of the cloned BCTV genomes were distinct from one another. Infectivity assays determined that plasmids containing tandem repeats of BCTV genomes were generally more infectious than excised linear DNA inserts. Progeny virus, derived from plants inoculated with cloned DNAs, differed in their ability to infect sugarbeet, Beta vulgaris L., and the severity of symptoms produced in B. vulgaris and other experimental hosts. PMID- 2230727 TI - Nucleotide sequence of rice dwarf virus genome segment 4. AB - The complete nucleotide sequence of rice dwarf virus (RDV) genome segment 4 was determined. Genome segment 4 was 2468 nucleotides long and had a long open reading frame initiating at nucleotides 64 to 66 and terminating at 2245 to 2247. The deduced polypeptide contained 727 amino acid residues with an Mr of 79.8K. Amino acid sequences similar to a 'zinc-finger' and purine NTP-binding motifs were present in the deduced polypeptide. Considerable amino acid sequence homology was detected between genome segment 4 of RDV and wound tumor virus (WTV). One of the sequences similar to the 'zinc-finger' motif was present in a conserved region of the polypeptide of both viruses. However, the sequence similar to the purine NTP-binding motif was not present in the polypeptide encoded by genome segment 4 of WTV. PMID- 2230728 TI - A classification of the tobamoviruses based on comparisons among their 126K proteins. AB - The products of partial proteolysis of the Mr 126,000 in vitro translation products of the RNA of eight tobamoviruses were separated by SDS-polyacrylamide gel electrophoresis. The peptide patterns obtained were compared using a computer program designed to establish phylogenetic relationships. The resulting most parsimonious phylogenetic trees grouped the tobamoviruses into clusters I (tobacco mosaic virus, tomato mosaic virus, tobacco mild green mosaic virus, pepper mild mottle virus) and II (sunn-hemp mosaic virus, cucumber green mottle mosaic virus, kyuri green mottle mosaic virus), with ribgrass mosaic virus in an intermediate position. This clustering resembles that obtained when the coat proteins of these viruses are compared. If the tobamoviruses have arisen by divergence from an ancestral type, the results suggest that different parts of the genome have diverged similarly and that recombination has not played a major role in the evolution of the group. PMID- 2230730 TI - Translation of cucumber necrosis virus RNA in vitro. AB - The in vitro translation products directed by cucumber necrosis virus (CNV) RNA were analysed in both rabbit reticulocyte lysate and wheatgerm extract cell-free translation systems. In rabbit reticulocyte lysates, one major protein of approximate Mr 34.6K was produced. In wheatgerm extracts, four proteins of approximate Mr values 41.6K, 34.6K, 24K and 20K were produced. The genomic locations of the CNV in vitro translation products were determined using several experimental approaches including, first, hybrid-arrested translation using negative-sense RNA corresponding to selected regions of the CNV genome, second, in vitro translation of synthetic positive-sense CNV transcripts and third, in vitro translation of CNV virion RNA fractionated according to size. Together these experiments demonstrated that the protein of Mr 34.6K is derived from the 5'-proximal coding region, the 41.6K protein is derived from an internal coding region, and that at least one but probably both the 24K and 20K proteins are derived from the 3'-terminal coding region. In addition, immunoprecipitation of in vitro translation products using anti-CNV polyclonal serum demonstrated that the 41.6K protein is the coat protein. The templates for the expression of CNV cistrons were investigated by in vitro translation of sucrose gradient fractionated CNV virion RNA as well as in vitro translation of positive-sense synthetic transcripts. PMID- 2230729 TI - Antigenic analysis of the coat protein of beet necrotic yellow vein virus by means of monoclonal antibodies. AB - By means of monoclonal antibodies (MAbs), five (groups of) epitopes were identified on particles of beet necrotic yellow vein virus (BNYVV). Epitopes 1 and 2, which were located on the opposite extremities of virus particles, are discontinuous (SDS-labile) epitopes which were destroyed when the particles were treated with trypsin. Epitope 3 is a continuous (SDS-stable) epitope located at the same extremity as epitope 2. It was not destroyed when the particles were treated with trypsin and was present on an Escherichia coli-expressed fusion protein containing amino acids (aa) 1 to 103 of the BNYVV coat protein. The continuous epitope 4, which was located along the entire length of the particles, was found to be present on a fusion protein containing aa 104 to 188 of the BNYVV coat protein but not on trypsin-treated virus particles. In Western blots, these treated particles yielded two slightly smaller coat proteins which failed to react with MAbs specific for epitope 4 but did react with polyclonal antisera and MAbs specific for epitope 3. BNYVV coat protein has a trypsin cleavage site on the carboxyl side of arginine in position 182, so it is therefore suggested that epitope 4 is located on the exposed C terminus, which is composed of aa 183 to 188. Epitope 5 was also located along the entire length of the particles but in a more uneven distribution than epitope 4. This may be because it is a discontinuous epitope that is very sensitive to subtle changes in protein conformation. PMID- 2230732 TI - Expression of the genome of potato leafroll virus: readthrough of the coat protein termination codon in vivo. AB - An antiserum was raised against a fusion protein containing part of the 56K polypeptide (P5) encoded by the open reading frame (ORF) at the 3' end of the genome of potato leafroll virus (PLRV). This antiserum reacted specifically with 80K and 90K polypeptides in PLRV-infected protoplasts, with a 90K polypeptide in infected potato tissue and with a 53K polypeptide in protein extracted from purified particles of PLRV. Monoclonal antibodies raised against purified PLRV particles also reacted with these polypeptides, as well as with the 23K coat protein. Virus particles partially purified from infected protoplasts contained some 90K polypeptide as well as the major 23K coat protein. The ORFs of the 23K coat protein and P5 are contiguous and in frame. The results suggest that the P5 polypeptide of PLRV occurs in infected cells as part of a readthrough protein comprising the 23K coat protein joined to the P5 amino acid sequence. Moreover the readthrough protein can be assembled into virus particles as a minor component together with the main 23K component. The P5 protein may thus contribute to properties of PLRV determined by its virus particle surface. PMID- 2230731 TI - Nucleotide sequence and evolutionary relationships of cucumber mosaic virus (CMV) strains: CMV RNA 3. AB - The nucleotide sequence of RNA 3 of two subgroup I strains of cucumber mosaic virus (CMV), Fny-CMV and M-CMV, was determined and compared at both the nucleic acid and protein level with the previously determined, corresponding (partial) sequences of RNA 3 of five other subgroup I strains: C-CMV, D-CMV, I17F-CMV, O CMV and Y-CMV. Fny-CMV RNA 3 is composed of 2216 nucleotides (nt) and M-CMV RNA 3 2214 nt. Both RNAs contain two open reading frames, the 3a gene and the coat protein gene. These RNAs showed very little nucleotide sequence divergence, either from each other or from the five other subgroup I strains. The nucleotide sequence variation observed was two to 13 differences in the 120 to 123 nt 5' non translated regions, six to 17 differences in the 840 nt 3a genes, two to 15 differences in the 296 to 299 nt intergenic regions, three to 25 differences in the 657 nt coat protein genes and two to 10 differences in the 299 to 303 nt 3' non-translated regions. Protein sequence similarity was also high, with one to four differences in the 279 amino acids of the 3a proteins and two to 13 differences in the 218 amino acids of the coat proteins. Limited nucleotide sequence variation among nine strains of CMV was also shown using an RNA protection assay and a probe specific for Fny-CMV RNA 3. The limited variation shown by RNA 3 of strains of CMV with different passage histories, isolated in different countries over a 50 year period, suggests that the maintenance of the highly conserved nucleotide sequence may be important for other viral RNA functions or interactions. PMID- 2230733 TI - Ribozymes that cleave potato leafroll virus RNA within the coat protein and polymerase genes. AB - Two ribozymes were synthesized which were designed to cleave potato leafroll virus (PLRV) positive strand RNA within the regions known to encode the viral coat protein and the predicted RNA polymerase gene. DNA sequences encoding the ribozymes were inserted into the Escherichia coli plasmids pTz18R and pTz19R under the control of the bacteriophage T7 promoter and enzymically active RNA molecules generated by transcription by T7 RNA polymerase in vitro. Each ribozyme cleaved its cognate site in RNA derived from either cDNA or PLRV particles. Ribozyme cleavage sites within the polymerase gene and coat protein gene were determined and shown to be at the predicted sequence immediately downstream from a GUC motif. An altered version of the ribozyme which recognized the sequence in the coat protein gene was isolated in which a single adenosine residue in the enzymic loop of the ribozyme was deleted. This mutated ribozyme was unable to cleave RNA molecules containing the coat protein ribozyme target site. PMID- 2230734 TI - Characterization of a potato leafroll luteovirus subgenomic RNA: differential expression by internal translation initiation and UAG suppression. AB - Northern blot analysis of Solanum tuberosum infected with potato leafroll luteovirus revealed the 6 kb genomic RNA and a major 2.3 kb subgenomic RNA. The 5' end of the subgenomic RNA was located at nucleotide 3653 in an intergenic region located at the centre of the viral genome upstream of three open reading frames (ORFs). Transient expression in tobacco and potato protoplasts of the beta glucuronidase reporter gene fused to various putative regulatory sequences present in the subgenomic RNA was used to study their influence on expression levels. We observed a suppression of the amber stop codon separating the coat protein (CP) gene from a downstream ORF (56K protein), to a level of 0.9% to 1.3%. Translation initiation at the AUG of an ORF (17K protein) which is nested within the CP gene, exceeds translation of the CP gene itself by a factor of 7. PMID- 2230735 TI - Attenuation of wild-type yellow fever virus by passage in HeLa cells. AB - During the 1960s three different research groups reported that passage of wild type yellow fever (YF) virus [strain Asibi (YF-Asibi)] in HeLa cells resulted in attenuation of the virus for monkeys so that the virus no longer caused viscerotropic disease. We have repeated and extended this observation to analyse the process of attenuation of YF virus during cell culture passage. A large plaque (LP) variant of YF-Asibi virus became attenuated for both monkeys and mice following six serial subcultures in HeLa cells (YF-Asibi-LP HeLa p6). Thus, attenuation was probably due to a genetic change in the virus population rather than to selective enrichment of a pre-existing variant of YF-Asibi-LP virus. No evidence was obtained to implicate defective interfering particles in the attenuation process. Comparison of the YF-Asibi-LP viruses before and after passage in HeLa cells, using a panel of envelope protein-reactive monoclonal antibodies (MAbs), showed that MAbs which specifically neutralize YF-Asibi-LP virus, and not YF 17D-204 vaccine virus, also neutralized YF-Asibi-LP HeLa p6. This indicated that the epitopes involved in the biological process of neutralization were not altered during attenuation. However, two MAbs that recognize envelope protein epitopes did distinguish between HeLa- and non-HeLa passaged YF-Asibi-LP virus. One of these (MAb 117) which is YF wild-type specific, recognized YF-Asibi-LP virus but not YF-Asibi-LP HeLa p6 virus, whereas the other (MAb411), which is YF vaccine-specific, recognized YF-Asibi-LP HeLa p6 virus but not YF-Asibi-LP virus. These results suggest that antigenic changes in the viral envelope protein may determine the relative virulence or attenuation of YF virus. PMID- 2230736 TI - Generation and transmission of Rift Valley fever viral reassortants by the mosquito Culex pipiens. AB - Reassortant viruses containing heterologous S and M genomic RNA segments were obtained from both mosquito and vertebrate hosts that had been coinfected with Egyptian and Senegalese strains of Rift Valley fever (RVF) virus. The origin of the S and M RNA segments in each plaque-cloned virus was determined with monoclonal antibodies capable of differentiating the nucleocapsid protein (S segment marker) or the G1 glycoprotein (M segment marker) of the parental strains. In the mosquito Culex pipiens, reassortants were detected after sequential ingestion of parental viruses by interrupted feeding on two infected hamster hosts, after feeding on a single host that had been infected with both parental strains, and from individual mosquitoes inoculated intrathoracically with both parental strains. Reassortant viruses replicated efficiently in mosquitoes and were readily transmissible by bite to hamsters. Replication of a second infecting strain of RVF virus was, however, completely inhibited if that virus was inoculated into a mosquito greater than or equal to 48 h after the first viral strain. Genetic reassortment may provide a mechanism for increased heterogeneity, and thus affect the epidemiology and evolution of RVF virus. PMID- 2230737 TI - Morphological studies of the neutralization of influenza virus by IgM. AB - Quantitative relationships between neutralization, aggregation and attachment to monolayers of chick embryo fibroblast (CEF) cells have been studied using a constant amount of influenza A/fowl plague virus/Rostock/34 (H7N1) and varying amounts of purified mouse polyclonal IgM directed against the haemagglutinin, the major viral neutralization antigen. There are two major types of interaction. (i) At low concentrations of IgM there is aggregation of virus, but no neutralization provided that the aggregates are dispersed by vortexing and dilution. Maximum aggregation occurs at less than seven molecules of IgM per virion and the IgM is probably bound in the 'staple' or 'crab' conformation at these concentrations. (ii) At higher concentrations there is neutralization and this coincides with inhibition of attachment of virus to CEF cells. Neutralization of 50% infectivity requires about 35 molecules of IgM per virion. The maximum neutralization observed was only 87%. Quantitative data and electron microscopy observations suggest that molecules of IgM at the higher concentrations adopt a planar stance approximately perpendicular to the viral surface. It appears that IgM neutralizes fowl plague virus in vitro primarily by interfering with its attachment to cells; the fraction of neutralized virus that does attach is known not be internalized. PMID- 2230738 TI - Variable regions on the genome of Malawi isolates of African swine fever virus. AB - Restriction enzyme site mapping showed that most BamHI and all ClaI sites were conserved on the genomes of 17 African swine fever virus isolates from separate disease outbreaks that occurred between 1982 and 1989 in Malawi. However, frequent variation between virus genomes did occur due to addition or deletion of DNA sequences at various positions along the genome and 11 virus genotypes could thus be distinguished among the 17 isolates analysed. Length variations occurred at 10 different loci on the virus genome. These variable regions were located between the left DNA terminus and a position up to 48 kb from that terminus, in the centre of the genome 90 to 93 kb from the left DNA terminus and between the right DNA terminus and a position 22 kb from that terminus. Length variations in most of these regions were small (less than 1 kb) but variations of about 4 kb occurred in a region up to 20 kb from the left DNA terminus. PMID- 2230739 TI - Biochemical and immunological studies of proteins from polydnavirus Chelonus sp. near curvimaculatus. AB - Polydnavirus from Chelonus sp. curvimaculatus (CcV) was purified and 18 structural polypeptides associated with CcV were identified by silver staining. Antibodies were raised against CcV protein and used in testing for ovary and in stung eggs. It was also established that the virus does not enter during the first 5 s of oviposition. Furthermore, no degradation of the virus proteins was Detected inside the egg within 2 h after oviposition. The glycoprotein nature of virus proteins was also determined by concanavalin A/horseradish peroxidase staining. The amino acid compositions of the most highly abundant peptides (41K, 33K, 21K, 17K and 13K) were determined, as was the N-terminal amino acid sequence of the 41K protein. The latter did not show similarity with any reported protein sequences. PMID- 2230740 TI - Restriction maps and sequence homologies of two densovirus genomes. AB - The genomes of Junonia coenia densonucleosis virus (JcDNV) and Galleria mellonella densonucleosis virus (GmDNV) were analysed by restriction endonuclease analysis and Southern blot hybridization. A total of 37 and 33 restriction sites were mapped on JcDNV and GmDNV DNA, respectively. BglI, HaeII and BstEII were site-specific for JcDNV DNA, and BglII and ClaI for GmDNV DNA. The two genomes had nearly identical maps for several restriction endonucleases and Southern blot hybridization using a total genomic JcDNV probe indicated extensive DNA sequence homologies spanning the entire length of the two genomes. Symmetrical cleavage sites, mapping at the extremities of both genomes, confirmed the presence of inverted terminal repeats of at least 420 to 440 bases in length. PMID- 2230741 TI - A synthetic peptide elicits antibody reactive with the native duck hepatitis B virus pre-S protein. AB - Synthetic peptides P37-49 and P63-79, derived from the pre-S region of duck hepatitis B virus (DHBV), have been synthesized. Only P37-49 was reactive with rabbit anti-DHBs/pre-S antibodies by radioimmunoprecipitation. Antiserum prepared against P37-47 reacted with a 35K polypeptide of native DHBs/pre-S by immunoblotting. It is concluded that P37-49 (MGQHPAKSMDVRR) mimics one of the epitopes of the DHBV pre-S antigen. PMID- 2230742 TI - Molecular analysis of the haemagglutinin gene of an avian H1N1 influenza virus. AB - This study presents the first nucleotide sequence and deduced primary amino acid sequence of a subtype H1 haemagglutinin from the avian influenza virus A/duck/Alberta/35/76 (H1N1). The molecule is structurally, antigenically and molecularly similar to H1 haemagglutinins of human viruses but sequence homology differences indicate that there has not been a recent transfer of haemagglutinin genetic information between them. PMID- 2230743 TI - Temperature elevation enhances cell surface expression of measles virus fusion protein in infected cells. AB - Cell fusion proceeded gradually in measles virus-infected cells incubated at 35 degrees C. Shift-up of incubation temperature to 39 degrees C induced rapidly increased cell fusion in spite of the cessation of de novo synthesis of the fusion (F) protein. Pulse-chase experiments showed that there was little difference in the acquisition of immunoreactivity by haemagglutinin (H) and F proteins between the two temperatures. H protein was detected on the cell surface 60 min after the chase at either temperature. However, appearance of F protein on the cell surface took less than 3 h at 39 degrees C whereas it took 5 h at 35 degrees C. These data indicate that temperature elevation induces more efficient expression of F protein on the cell surface accompanied by marked syncytium formation in measles virus-infected cells. PMID- 2230744 TI - Potato virus Y helper component protein is associated with amorphous inclusions. AB - The distribution of the helper component (HC) protein of potato virus Y in tissues and cells of infected plants was studied by immunoblotting and immunogold labelling techniques. This HC protein was found in leaf blade and vein tissue but not in the petiole of leaves. In infected cells, the protein was localized in rod shaped cytoplasmic inclusions known as amorphous inclusions. PMID- 2230745 TI - Psychological functioning in a cohort of gay men at risk for AIDS. A three-year descriptive study. AB - This study describes the mental health of a large cohort of gay men participating in the Chicago Multicenter AIDS Cohort Study/Coping and Change Study. Six biannual questionnaires were self-administered between 1984 and 1988. General mental health was determined by the Hopkins Symptom Checklist (HSCL). An abbreviated version of the Center for Epidemiologic Study Depression Scale (CESD 5) and an adapted Diagnostic Interview Schedule (DIS) question also measured depression. Suicidal ideation was assessed by one question in the HSCL. AIDS specific distress was determined by three subscales specifically developed for this study. While mean HSCL and CESD-5 scores were stable during the observational period, AIDS-specific distress increased over time. The HSCL scores for the cohort were somewhat elevated above general population norms but considerably below psychiatric outpatient norms. Fewer than 12% of the men reported elevated HSCL or CESD-5 scores three or more times. A self-reported episode of depression of two weeks or more, measured by the DIS screening question, was experienced by 40.1% of the sample. Suicidal ideation was reported on three or more visits by 18.8% of the men. The younger members of this cohort exhibit greater general and AIDS-specific distress. Income was inversely associated with general distress. HIV-seropositive participants had generally higher AIDS-specific distress scores than those who were seronegative, but their scores were equivalent on the HSCL and CESD-5. PMID- 2230746 TI - Visual information processing in positive, mixed, and negative schizophrenic syndromes. AB - The purpose of this study was to determine whether schizophrenics with positive, mixed, and negative syndromes are distinguished in terms of visual stimulus registration thresholds and efficiency of information processing. Forty-five schizophrenic inpatients were classified accordingly into groups of 15 each and compared with one another and with 15 normal control subjects on a visual backward masking task. Repeated-measures analysis of variance revealed that all three schizophrenic groups were less efficient information processors than were normal subjects. Relative to the positive group, the negative group displayed significantly longer registration thresholds, fewer correct target stimulus detections, and longer time intervals to achieve their first significant improvement in performance and to first exceed chance response levels. The three syndrome groups were not significantly different in their rates of improvement over trials. Secondary correlational analyses showed that the information processing measures were unrelated to a variety of demographic, psychiatric, and cognitive developmental variables, although shorter recognition thresholds and shorter unmasking interval scores were associated with faster psychomotor rates. Complex interrelationships were uncovered between the information-processing measures, positive and negative symptomatology, and general psychopathology. The results were interpreted as supporting the validity of the positive-negative distinction for explaining some of the heterogeneity in schizophrenia. PMID- 2230747 TI - Dimensions of personality disorder. The DSM-III-R cluster A diagnoses. AB - The authors adopt a construct validity approach to examine the structural validity of diagnoses of paranoid, schizoid, and schizotypal personality disorders. Systematic descriptions of these diagnoses were developed based on features identified from the literature that were organized using the clinicians' ratings. Each diagnosis was described in terms of a series of behavioral dimensions. Sets of behavioral exemplars were developed to assess each dimension. Dimensions and diagnoses were found to exhibit satisfactory levels of internal consistency that were cross-validated in a general population sample of 274 subjects and a clinical sample of 133 patients with a diagnosis of personality disorder. Some dimensions did not correlate highly with the total diagnosis score. Diagnoses could probably be refined by eliminating these dimensions. The structural relationships between dimensions delineating each diagnosis were explored using factor analysis. Diagnoses were not unifactorial. Instead, each diagnosis was found to be composed of two factors. The factorial structure of each diagnosis was found to be similar in the general population and clinical sample. It is suggested that the results support a dimensional representation of these diagnoses using three dimensions: paranoid behaviors, social avoidance, and perceptual cognitive distortion. PMID- 2230748 TI - Compliance, reliability, and validity of self-monitoring for physical disturbances of Parkinson's disease. The Parkinson's Symptom Diary. AB - Previous clinical research in Parkinson's disease has recognized the value of self-monitoring procedures in which patients observe and record the frequency and severity of their own symptoms as these occur within the patient's social and work environment. We discuss issues of methodology and report a study of compliance, test-retest reliability, and validity with a new self-monitoring instrument, the Parkinson's Symptom Diary. Two recordings of frequency (loss of balance, hesitation-freezing) and two ratings of severity (tremor, difficulty walking) were made four times daily for one week by patients (N = 73) who were without apparent loss of cognitive or memory functions. A total of 91% of the diaries received (97% of requested) met strict compliance criteria so that independent sampling over days could be assumed. Test-retest stability over one month was demonstrated for each score (all Spearman rho greater than .85) in a representative subsample of 28 patients. Criterion validity was demonstrated for each score by an expected pattern of correlations with independently obtained observer ratings of the same or related indices of disease, and by comparison with Hoehn and Yahr disability stages. By its simplicity, this self-assessment device can be an invaluable complement to traditional methods of clinical and laboratory assessment in the care and evaluation of Parkinson patients. PMID- 2230749 TI - Significance of cocaine history in schizophrenia. AB - Fifty-one schizophrenic inpatients were divided into two groups, those with and without history of cocaine use, and compared on historical, demographic, cognitive, and psychopathological measures. Patients with a cocaine history were found to be significantly more depressed, less socialized, and more impaired in conceptual encoding and verbal memory, while less disordered in attention. The two groups did not differ in severity of illness or positive and negative syndromes. There were also no differences in control variables such as age, gender, education, intelligence, premorbid adjustment, neuroleptic dose, onset and chronicity of illness, continuity of hospitalization, paranoid subtype, and psychiatric illness in the family. Cocaine history was associated with multiple illicit drug use, but for other substances there was no increased liability for depression or cognitive deficits. The results suggest that the clinical presentation in schizophrenia is significantly associated with prior cocaine experience. PMID- 2230750 TI - The empathic process and its mediators. A heuristic model. AB - Clinical empathy research has been plagued with conceptual and methodological difficulties. This paper describes a model of the empathic process that enables clinicians, teachers, and researchers to examine specific components of the model and to determine the influence of particular mediators on the empathic process. Empathy is conceptualized as a three-phase time-sequenced process rather than as a multidimensional or multicomponent phenomenon. Stripped of detail, the empathic process reveals an inducement phase, a matching phase, and a participatory helping phase. By examining these phases, it becomes possible to distinguish empathy from closely related concepts such as sympathy. Each of the phases reveals numerous mediating variables that influence the outcome of the phase, i.e., whether the process of empathy continues or an alternate terminal point is reached. Many of these mediators are derived from existing conceptual and empirical work on empathy. Particular attention is paid to situational or contextual mediators of empathy. Contextual mediators have only recently been acknowledged as an important variable in the empathic process. For clinicians, identification of contextual variables that may be responsive to intervention is a critical step in the modification of the clinical environment. We would suggest that clinical empathy research is largely the study of these mediating influences and should be recognized as such. PMID- 2230751 TI - Hyperemesis gravidarum as conversion disorder. AB - Psychosocial factors have long been believed to be important in the pathogenesis of emesis gravidarum (morning sickness) and hyperemesis gravidarum (HG). Although this has been confirmed during extensive studies over the last 30 years, HG has never been described as a conversion reaction. We describe two women presenting with hyperemesis who clearly fulfill diagnostic criteria for conversion. We suggest that strong psychodynamic conflicts are expressed by this potentially dangerous symptom in a subset of individuals and that dynamic interventions have a role in treating certain patients with HG. PMID- 2230752 TI - Dropping objects: possible mild cataplexy associated with clozapine. PMID- 2230753 TI - Untying the gordian knot: the genetics of Tourette syndrome. AB - A review of the current status of the genetics of Tourette syndrome is presented. Over the course of the 104 years since Gilles de la Tourette described the syndrome that bears his name, a body of carefully collected, described, and analyzed data has produced a model of the genetics that implicates a single dominant gene that is variably penetrant in males and females. Moreover, the locus of action of this gene is most likely in the dopaminergic system of the midbrain. A systematic search for this gene using recombinant DNA techniques is under way. PMID- 2230754 TI - Prevalence of mental disorders after catastrophic financial loss. AB - In a controlled study, the authors determined the risk of developing major mental illness after catastrophic financial loss. Seventy-two adults who lost their retirement savings in a bank fraud were interviewed using the Diagnostic Interview Schedule. Major depression by DSM-III criteria was present in 29% of the victims during the first 20 months after their loss as compared with 2% of 66 age, gender, and residential area-matched control subjects (p less than .0001). Generalized anxiety disorder as defined by DSM-III criteria was experienced by 27% of victims after the loss as compared with 10% of control subjects (p = .03). After the loss, victims had lower subjective health ratings, more functional somatic complaints, and higher tranquilizer usage than control subjects. There was no difference between depressed and nondepressed in types of coping responses or use of social supports and confidants. Only four of 21 victims who suffered major depression sought help from a mental health professional. We conclude that catastrophic financial loss may result in the onset of major depressive disorder and generalized anxiety disorder. PMID- 2230755 TI - DSM-III personality disorder dimensions. AB - Dimensional scores were computed for the 11 DSM-III personality disorders (PDs) in 797 relatives of psychiatric patients and never ill control subjects interviewed with the Structured Interview for DSM-III Personality Disorders. The distribution of scores for all 11 PD dimensions was skewed to the right. A principal components analysis with varimax rotation produced three factors that closely corresponded to DSM-III's suggested clustering of the PDs into eccentric, dramatic, and anxious types. Men scored significantly higher on the paranoid, schizoid, compulsive, antisocial, and narcissistic dimensions, whereas women had significantly higher histrionic, dependent, and avoidant scores. Age was negatively correlated with most of the PD dimensions, and the correlations were strongest with the four PDs in cluster 2 (histrionic, antisocial, narcissistic, and borderline). Each of the eight axis I disorders examined was associated with increased axis II pathology. PMID- 2230756 TI - DSM-III personality disorders among patients with major depression, anxiety disorders, and mixed conditions. AB - Of 298 mainly nonpsychotic psychiatric outpatients between 19 and 59 years of age, a group of patients having either pure major depression, major depression in combination with anxiety disorders, or pure anxiety disorders was extracted. The anxiety disorders were further differentiated in panic and nonpanic anxiety disorders. The groups were compared as to differences in frequency of personality disorders assessed by means of the Structured Interview for DSM-III Personality Disorders. The mixed major depression/anxiety disorder group appeared to be the most deviant with more severe personality disorders such as paranoid and borderline in addition to avoidant and dependent personality disorder. The differentiation between panic and nonpanic anxiety showed that it was patients with nonpanic anxiety features in addition to major depression who had this higher frequency of personality disorders. These findings imply that it is important to distinguish between major depression cases with and without anxiety disorders both in forthcoming research and in clinical practice. PMID- 2230757 TI - The effect of personality on placebo response in panic patients. AB - Twenty-eight patients who participated as a placebo group in a treatment study of panic disorder were studied to determine the effect of personality on study completion and outcome. Those subjects who completed only 3 weeks had significantly more pathological personality traits than those who continued in the study. For those continuing beyond 3 weeks, there were negative correlations between the paranoid and borderline personality traits and a global outcome measure. Spontaneous panic attacks were not affected by personality. PMID- 2230758 TI - Correlates of Korean immigrants' mental health. AB - The main objectives of this paper are an empirical investigation of major structural and situational variables related to Korean immigrants' mental health and a theoretical exploration of the meaning of the empirical findings. As part of a larger epidemiological research, the data for this paper derive from diagnostic interviews of 622 Korean immigrants (20 years and older) residing in the Chicago area. Data analyses reveal that, among the respondents in general, those who are married, highly educated, and currently employed in a high-status occupation indicate better subjective mental health (less demoralized and more satisfied with life) than others. Of other variables examined, however, significant gender differences in the correlates of mental health are observed. For the male immigrants, a set of work-related variables is clearly the strongest correlate of their mental health, whereas no such distinctive set of variables accounts for the female immigrants' mental health. Nevertheless, the family life satisfaction and several ethnic attachment variables are moderately related to the female immigrants' mental health. Theoretical implications of these findings are discussed in light of the confluence of ethnic attachment and acculturation on immigrants' mental health. PMID- 2230759 TI - Classification of natural and supernatural causes of mental distress. Development of a Mental Distress Explanatory Model Questionnaire. AB - This paper describes the background and development of a Mental Distress Explanatory Model Questionnaire designed to explore how people from different cultures explain mental distress. A 45-item questionnaire was developed with items derived from the Murdock et al. categories, with additional items covering western notions of physiological causation and stress. The questionnaire was administered to 261 people, mostly college students. Multi-dimensional scaling analysis shows four clusters of mental distress: a) stress; b) western physiological; c) nonwestern physiological; and d) supernatural. These clusters form two dimensions: western physiological vs. supernatural and impersonal vs. personalistic explanations. Natural and stress items are separated from supernatural and nonwestern physiological items along the first dimension. Brain damage, physical illness, and genetic defects have the greatest separation along the first dimension. Being hot, the body being out of balance, and wind currents passing through the body most strongly represent the non-western physiological category. The questionnaire has the potential to be used for community health screening and for monitoring patient care, as well as with students in the health sciences and with health practitioners. PMID- 2230760 TI - State-dependent tardive dyskinesia. PMID- 2230761 TI - Our race to the future. AB - The need for mosquito control is documented from history books with comments about hoards of mosquitoes, deaths from mysterious high fevers, and yellow fever, malaria and dengue. The paper traces the birth of mosquito control in the United States to the present time with a look into the future. Regulations are discussed and their effect on mosquito control methods. Public education and training of personnel is mentioned. The author's opinion of AMCA's role in the future of mosquito control and research is one of prominence and leadership. PMID- 2230762 TI - Apparent influence of the stage of blood meal digestion on the efficacy of ground applied ULV aerosols for the control of urban Culex mosquitoes. I. Field evidence. AB - The impact of ULV resmethrin on urban Culex mosquitoes was evaluated in 4 field trials by monitoring daily oviposition rate. A well-defined oscillation of effect, with a period corresponding to the duration of the gonotrophic cycle, was observed. We postulate that this oscillation arises from changes in susceptibility following blood feeding and/or behavioral factors. The data indicate that a single treatment with ULV may be inadequate for the effective control of vector mosquitoes. PMID- 2230763 TI - Apparent influence of the stage of blood meal digestion on the efficacy of ground applied ULV aerosols for the control of urban Culex mosquitoes. II. Laboratory evidence. AB - The susceptibility of adult Culex pipiens s.l., Culiseta melanura and Aedes aegypti to insecticide aerosols in wind tunnel exposures varied with time, depending on the stage of blood meal digestion. Greater than 2-fold differences were observed in the concentrations of malathion and synergized resmethrin required to kill test mosquitoes, depending on whether they had been given a blood meal and, if they had, the length of time following the blood meal. The period of lowest susceptibility varied from 24 h after feeding in Ae. aegypti to 72 h in Cs. melanura. The greatest variability occurred during the period when undigested blood was present. Data from tests with a malathion-tolerant strain of Cx. pipiens s.l. suggested little change in susceptibility regardless of blood feeding and the associated weight changes that occur from ingestion of blood. PMID- 2230764 TI - Apparent influence of the stage of blood meal digestion on the efficacy of ground applied ULV aerosols for the control of urban Culex mosquitoes. III. Results of a computer simulation. AB - When posttreatment response to ultra low volume (ULV) application of insecticide has been followed for periods approaching a week, a damped oscillation in oviposition rates is observed, probably because females who have been recently blood-fed are more resistant to insecticides than their unfed siblings. We describe a simple model (ULVSIM) that incorporates physiologic changes in insecticide susceptibility and accounts for much of our field data. The model follows 30 cohorts over 30 days following insecticidal treatment. Multiple treatments or short-term residual activity can be evaluated. The model predicts that oviposition will follow a pattern of damped oscillations after an adulticidal treatment. The model gave a good fit to oviposition data obtained in 2 field trials of resmethrin for 7 to 9 days after treatment. It can be used to evaluate the effect of single and multiple treatments on the total female Culex population and on numbers of infected females surviving for different periods following an infective blood meal. PMID- 2230765 TI - Fate and persistence of Bacillus sphaericus used as a mosquito larvicide in dairy wastewater lagoons. AB - The fate and persistence of the mosquitocidal bacterium, Bacillus sphaericus, in dairy wastewater lagoons was evaluated in conjunction with trials of its larvicidal efficacy against Culex stigmatosoma. Two commercial formulations, BSP 2 (at 4.48 kg/ha) and ABG-6184 (at 2.24 kg/ha) gave about 90% reduction for up to 4 weeks, although surface water lost its insecticidal activity by 3 days posttreatment. Spores settled to the bottom within 3 days of treatment, but could be recovered in surface water after reflooding. Spore concentrations in bottom water varied widely, yet insecticidal activity remained high for from 3 days (BSP 2 at 4.48 kg/ha) to 2 weeks (ABG-6184 at 2.24 kg/ha). Spores persisted in the mud throughout the study period. These results indicate the extended control obtained was due primarily to the ingestion of spores from bottom water and mud by larvae, which routinely inhabit the shallow areas toward the edge of the pond and browse at the pond bottom. PMID- 2230766 TI - Habitat and temporal partitioning of tree hole Culicoides (Diptera: Ceratopogonidae). AB - Spring emergence patterns of tree hole Culicoides were examined at 11 geographic locations. Habitat selection was one mechanism of partitioning used by Culicoides. One group (3 species) occupied tree holes with standing water (wet), while the other (7 species) inhabited tree holes without standing water (dry). The wet tree hole species had sustained emergence patterns, emergence maintained over several consecutive weeks. The dry tree hole species had phasic or biphasic emergence lasting fewer days or occurring as 2 short periods. In both dry and wet habitats, species emerged in a temporal sequence. This temporal sequence was disrupted if a species occupied a type of tree hole (wet/dry) from which it did not normally occur. PMID- 2230767 TI - Correlation of nutritional reserves with a critical weight for pupation in larval Aedes aegypti mosquitoes. AB - The relationships between the readiness of fourth instar Aedes aegypti to metamorphose and their weight, nutritional reserves and sex were examined. Both the critical larval weight required for metamorphosis and the potential weight were influenced by the temperature at which the larvae were reared, and were greater for females than for males. Caloric levels of soluble carbohydrates and soluble lipids correlated strongly with weight. The accumulations of both carbohydrates and lipids were sex-dependent and were increased in both sexes at the higher temperature, but caloric levels of glycogen at the critical weights were all similar. We suggest that weight per se is not a critical factor in determining readiness to pupate, and that carbohydrate levels may be one important causal variable. PMID- 2230768 TI - A genetic study of the malaria vector Anopheles nuneztovari from western Venezuela. AB - A photomap of larval polytene chromosomes of Anopheles nuneztovari (population B) from western Venezuela is presented. Samples of An. nuneztovari B taken from 4 study sites in the states of Barinas and Tachira comprise a single panmictic population, which is chromosomally identical to the cytotype identified by Kitzmiller et al. (1973) from western Venezuela and Colombia. The frequency of polymorphism 2La has increased significantly in the 16 years that have elapsed since the 1973 study. In addition, inversion 2La does not conform to Hardy Weinberg equilibrium. These 2 changes are most likely due to environmental alterations which have resulted in the heterozygous condition becoming more locally adaptive. PMID- 2230769 TI - Mosquito attraction to substances from the skin of different humans. AB - Mosquito attraction responses to substances collected from human skin and placed on glass petri dishes were studied. Mosquito response varied according to the source of the substance. Substances removed from the head and hands elicited the greatest attraction response in laboratory-reared mosquitoes. Mosquito response lasted up to 6 h when the substance was aged and was increased by warming the samples from ca. 25 degrees C to 37 degrees C. Of the 12 mosquito species studied, attraction response was greatest in Aedes aegypti. It is cautioned that residues deposited by handling traps or other apparatus used in mosquito studies may influence test results. PMID- 2230770 TI - Differences in the larval alarm reaction in populations of Aedes aegypti and Aedes albopictus. AB - The time spent submerged during the larval alarm reaction was measured for several strains of Aedes aegypti and Ae. albopictus from different locations. Differences between the 2 species were not significant. Differences in strains within the species were highly significant. Greater differences were seen among strains of Ae. albopictus than among strains of Ae. aegypti. These differences represent an additional indication of extensive local differentiation in Ae. albopictus. PMID- 2230771 TI - Distribution of the sibling species of Anopheles farauti in the Cape York Peninsula, northern Queensland, Australia. AB - The sibling species of Anopheles farauti s.l. were collected in larval and adult surveys from 34 localities on Cape York Peninsula and were identified by isoenzyme electrophoresis. The most common species near the coast was An. farauti 1 which was often found breeding within 100 m of the sea in either brackish or freshwater habitats. Larvae of the other 2 species were not found in brackish water which accords with previous laboratory observations of their lower salinity tolerance. Anopheles farauti 2 appears to have the widest distribution of the 3 sibling species on Cape York Peninsula as it was common in both coastal and inland localities. Anopheles farauti 3 was rarely found near the coast. In one locality at Lockhart River near the east coast of the peninsula larvae of the 3 species were found together in a small muddy creek. PMID- 2230772 TI - Comparison of the effectiveness of two formulations of deet against Anopheles flavirostris. AB - The effectiveness of 2 formulations of deet (diethylmethylbenzamide) was tested against the principal vector of malaria in the Philippines, Anopheles flavirostris. A new extended duration repellent formulation (EDRF) was compared with the standard military-issue liquid formulation. The EDRF was significantly more effective than the liquid formulation between 6 and 12 h post-application. There was no difference between the 2 formulations in the first 6 h following application, or between 12 and 15 h post-application. The continued usefulness of the liquid formulation is discussed in light of these results. PMID- 2230773 TI - Factors affecting the human-feeding behavior of anopheline mosquitoes in Egyptian oases. AB - Blood meals were tested by a direct enzyme-linked immunosorbent assay (ELISA) for 424 Anopheles sergentii and for 63 An. multicolor collected in Siwa, Farafra and Bahariya oases in the Western Desert of Egypt. Both species were highly zoophilic. Human blood-feeding by An. sergentii was less common in Bahariya (2.3%) and Farafra (1.3%) than in Siwa (15.3%). A likely explanation is that large domestic animals are held at night inside houses in Bahariya and in Farafra whereas in Siwa, animals are usually housed outdoors in sheds. These patterns of An. sergentii human-feeding behavior may contribute to the persistence of low level Plasmodium vivax transmission in Siwa in contrast to negligible or no transmission in Bahariya and Farafra. PMID- 2230774 TI - Isolation of Jamestown Canyon virus (California serogroup) from Aedes mosquitoes in an enzootic focus in Michigan. AB - Twenty isolates of Jamestown Canyon virus were obtained from adult females of 5 Aedes species collected at the Houghton Lake Wildlife Research Area, Missaukee County, in north-central Michigan between 1985 and 1989. Fourteen were from Aedes provocans, and 6 were from 4 other snowmelt Aedes species. One isolate of trivittatus virus and one Cache Valley-like virus were also obtained. Seasonal succession patterns for numerous mosquito species were recorded over 4 years. The temporal association of adult mosquito emergence, virus isolations, and infection and seroconversion of sentinel deer suggest that Ae. provocans is a primary enzootic vector of Jamestown Canyon virus in that focus. We hypothesize that Ae. provocans provides an overwintering reservoir for Jamestown Canyon virus at the study site. A large dry ice-baited "tent trap" was the most productive method for collecting numerous aedine and other mosquito species. PMID- 2230775 TI - Attraction of mosquitoes to diethyl methylbenzamide and ethyl hexanediol. AB - Studies by prior workers have shown that insect repellents can act as attractants when present as low concentrations, deposits or residues. In the present study deet and ethyl hexanediol were tested in 2-fold serial doses from 1.9 X 10(-9) to 1.6 X 10(-2) mg/cm2 on the forearms of volunteers against colonized Anopheles albimanus, Aedes aegypti and Ae. taeniorhynchus. Both compounds were significantly repellent at the high end of the dose range, as expected. Neither was significantly attractant to An. albimanus in low doses. However, deet was significantly attractant to Ae. aegypti in the dose range 7.6 X 10(-9) to 1.2 X 10(-4) mg/cm2 and to Ae. taeniorhynchus in the dose ranges 1.9 X 10(-9) to 3.1 X 10(-8) mg/cm2 and 2.0 X 10(-6) to 2.5 X 10(-4) mg/cm2. Ethyl hexanediol was significantly attractant to Ae. taeniorhynchus in the dose range 1.9 X 10(-9) to 6.2 X 10(-5) mg/cm2. Based on these results and prior work of V.G. Dethier and C.N.E. Ruscoe, a model sequence of the effects of chemicals on insects with increasing dose was developed. It was concluded that the labels of commercial repellents should be amended to include instructions to wash off or reapply the repellent when it is no longer effective. PMID- 2230776 TI - Anopheles dirus species E: chromosomal and crossing evidence for another member of the dirus complex. AB - Cytogenetic and crossing data provide strong evidence for the existence of another species, dirus E in southwestern India, within the Dirus Complex of Anopheles. These findings are in accord with unpublished morphological observations. Our data suggest a significant genetic divergence between species E and its close relatives, An. dirus A, B and C in Thailand. These data also suggest that dirus E is an incipient sibling species of its geographically nearest relative, dirus D, and that it seemingly co-evolved through the process of allopatric speciation. PMID- 2230777 TI - Nectar feeding activity of Aedes mosquitoes, with special reference to Aedes communis females. AB - A total of 5,721 mosquitoes (6% males) of 16 species were collected with an aerial net, when attracted to the investigator, during May-August 1984 at 2 sites in central Sweden. The majority of the mosquitoes collected (63%) were Aedes communis. Aedes communis females at both localities showed peak flight activity at evening twilight. At one site, a diel pattern of nectar feeding was correlated with host seeking activity; at the other site no correlation was found. Seasonal differences in mean fructose content of the mosquitoes were found. Among the 94 blood-fed females (belonging to 6 species) that were collected, 71% were fructose positive (n = 67) and in different ovarian stages. PMID- 2230778 TI - Estimation of absolute numbers of damselfly nymphs (Odonata: Coenagrionidae) by dipper sampling in California rice fields with seasonal, spatial distributions and vegetation association. AB - Estimates of relative and absolute density in rice field populations of damselfly nymphs (predominantly Enallagma civile with few Ischnura denticollis) were compared using the regression method. An equation, X = Y divided by 0.0016, allows estimation of absolute density (X) from a relative density index (Y, dipper count). In the rice growing area of Fresno, California, nymphal population peaks appeared during June and August approaching 3-5 million per 0.405 ha (1 acre). Spatial distribution was theoretically represented fairly well by a negative-binomial distribution. The degree of clumping is one of overdispersed types; it is especially classified as a model of randomly distributed colonies with mean colony size fixed. Presence or absence of submerged vegetation markedly affected damselfly nymphal density but the biomass of submerged or emerged vegetation was not a significant factor. PMID- 2230779 TI - Evaluation of Bacillus sphaericus 2362 against Culex quinquefasciatus in septic ditches. AB - Four application rates of Bacillus sphaericus strain 2362 were tested for efficacy in septic ditches against Culex quinquefasciatus 2nd-4th instar larvae. Trials were conducted over a 2-year period. In 1987, all dosages applied to dairy effluent ditches resulted in substantial reductions after 48 h. Differences among dosages did not differ significantly (P greater than or equal to 0.05). After 5 days, mosquito larval numbers increased with dosage rates of 0.6, 0.9 and 1.2 liters/ha. Residual control was maintained, however, at 2.4 liters/ha for 17 days. In 1988, B. sphaericus applied to domestic sewage effluent ditches at rates of 1.2 liters/ha, and 2.4 liters/ha induced greater than 79% suppression for a period of 15 days, and the 1.2 liters/ha rate induced greater than 79% suppression for a period of 20 days. A rate of 0.9 liters/ha provided good to excellent control (greater than 88%) for a period of 10 days. A rate of 0.6 liters/ha produced less than 50% suppression after 48 h. PMID- 2230780 TI - Larvicidal effects of grain sorghum (Sorghum bicolor) seedling extracts upon Culex pipiens larvae. AB - A study of laboratory and field reared 2nd and 3rd instar Culex pipiens larvae suggests that extracts from 2 varieties of Sorghum bicolor seedlings are significant (P less than 0.05) larvicides under laboratory conditions. These plant extracts contain the organic cyanogen dhurrin and were calibrated to produce 90% mortality in 2nd instar Culex pipiens larvae at 0.82 ppm and 90% mortality in 3rd instar larvae at 1.12 ppm. A preliminary behavioral assessment of late 3rd instar larvae exposed to 1.42 ppm suggests that these plant extracts produce 80% mortality after only 4-5 h of contact. Plant extracts appear stable when stored at up to 32 degrees C in a closed container. Once the extracts are infused in water and exposed to air, however, they biodegrade after 24 h. These laboratory results emphasize the need for field tests against natural populations of Culex pipiens and nontarget organisms. PMID- 2230781 TI - Incrimination of Aedes provocans as a vector of Jamestown Canyon virus in an enzootic focus of northeastern New York. AB - A 2-year field study was conducted in southern Saratoga County, New York, to determine which species of the Aedes communis group mosquitoes were potential vectors of Jamestown Canyon (JC) virus. A total of 23,890 mosquitoes (890 pools) were processed for virus isolation in 1988-89, yielding 17 JC virus isolates from Ae. provocans and one isolate each from Ae. communis, Ae. intrudens and Ae. punctor. Minimum field infection rates (MFIR) and daily MFIRs as high as 1:219 and 1:38, respectively, were found in adult female Ae. provocans. Virus isolation attempts from an additional 394 individual Ae. provocans produced a seasonal field infection rate (FIR) of 1:131 and daily FIRs of 1:71 and 1:22. Evidence of transovarial transmission of JC virus was demonstrated by the isolation of virus from 2 pools each of 50 male Ae. provocans reared in the insectary from pupae collected at the study site in 1989. We conclude that Ae. provocans is a potentially important vector of JC virus in northeastern New York. PMID- 2230782 TI - Colonization and maintenance of Anopheles deaneorum in Brazil. AB - Anopheles deaneorum, an important malaria vector and a member of the Anopheles albitarsis complex, was colonized by an artificial mating technique. Morphological and behavioral differences between An. deaneorum and An. albitarsis from Costa Marques, Rondonia, Brazil, are discussed. The essential methods and colonization techniques are described. Immature development and mortality rates were reduced when dried grass was added to larval rearing pans. Males frequently mate more than once using the force mating technique. However, insemination and larval eclosion rates decline as males are successively mated with unmated females. PMID- 2230783 TI - Baseline data on Aedes aegypti populations in Santo Domingo, Dominican Republic. AB - Baseline field studies were conducted from April 1987 to July 1988 on Aedes aegypti in Santo Domingo, an endemic area for dengue fever. Premise, container and Breteau indices were measured in one treated area and 2 nearby control areas. These indices averaged 69.6, 46.3 and 142.1, respectively. The principal larval habitats of Ae. aegypti were 208-liter (55-gal) concrete-lined drums. The estimated daily adult production was approximately 60 per house. Adult mosquito populations were monitored using oviposition traps and by sweep net collections. There was no correlation between adult abundance and the larval indices. Monitoring the natural adult densities was more efficient for evaluating the impact of ULV malathion application than the use of standard bioassay procedures. PMID- 2230785 TI - Ovipositional response of Aedes triseriatus females to horizontally and vertically open ovitraps in southern Illinois. AB - Aedes triseriatus oviposition in standard, horizontally open (open top) ovitraps was compared with that in vertically open (open-sided) ovitraps during 1989 in a deciduous woodland in southern Illinois. This comparison was to determine whether female oviposition preference changed as a result of seasonal photoperiod changes. Results show that Ae. triseriatus females prefer horizontally open ovitraps regardless of whether they are depositing eggs which hatch shortly after deposition or whether the eggs diapause because of shortened late summer/early fall photoperiods. PMID- 2230784 TI - Effects of controlled burning on Aedes taeniorhynchus eggs in an abandoned rice impoundment in South Carolina. AB - Controlled burning reduced the number of viable eggs in an Aedes population. The effectiveness of the burn was related to the amount of rainfall, surface moisture and dry vegetation. A greater reduction in viable eggs occurred when the burn was close to the ground. Variable results were achieved if the surface was moist but there was a significant reduction in the number of viable eggs, due to a heavy amount of dry vegetation accompanied by low rainfall. PMID- 2230786 TI - A new housing for the Battery-operated Aerosol Droplet Sampler Model 312. AB - Rotating impactors are more efficient aerosol droplet collectors than stationary impactors. Breakage of the phenolic plastic housing on a commercial rotating impactor during shipment has reduced this laboratory's ability to collect droplet data. Directions for replacing that housing with an aluminum BUD box are presented. PMID- 2230787 TI - Routine blood-feeding of Aedes aegypti via a new membrane. PMID- 2230788 TI - Comparison of New Jersey light traps for collection of adult Culicoides variipennis (Diptera: Ceratopogonidae). AB - Comparisons between standard incandescent New Jersey and modified ultraviolet New Jersey light traps were made. Both trap types collected the same proportions of males, nulliparous, parous empty, gravid and blood engorged female Culicoides variipennis. Although both traps were highly attractive to females that had taken at least one blood meal, the black light trap collected ca. 10-fold more parous empty and gravid flies than the incandescent and would therefore be recommended for use in trapping C. variipennis for virus assay. PMID- 2230789 TI - Distribution of Culex tarsalis larvae in a freshwater marsh in Orange County, California. AB - The distribution and abundance of mosquito larvae in a freshwater marsh were determined during a low water period in the late summer. Culex tarsalis larval abundance was significantly associated with the percent cover by Typha spp. root masses and Typha spp. stem density in 1-m2 quadrants. Larval mosquito abundance was not significantly related to bulrush (Scirpus californicus) stem density, position in the marsh (transect compass direction), position in the inundated vegetation on each transect or several physicochemical factors. As water levels decline seasonally, mosquito developmental sites in San Joaquin Marsh change from mats of decaying vegetation to cattail root masses. PMID- 2230790 TI - Analysis of the gut contents of naiads of Enallagma civile (Odonata: Coenagrionidae) from a Texas pond. AB - Foregut contents of naiads of the damselfly species, Enallagma civile, collected from a permanent pond, were analyzed to determine the natural prey for immatures of this species. The analyses revealed the naiads containing prey had fed predominantly on chironomid larvae. Corixid, cladoceran, ostracod and aquatic mite remains were found in some of the naiad specimens examined. However, no remains of mosquito larvae were detected in any of the specimens, even though mosquito larvae were observed as being continuously present in the pond sites where the naiad specimens were collected. PMID- 2230792 TI - Five kingdoms--reflections upon the classification of organisms. PMID- 2230791 TI - Records of Aedes albopictus, Ae. aegypti and Ae. triseriatus from the U.S. Air Force ovitrapping program--1989. AB - During 1989, ovitrapping was conducted by 36 U.S. Air Force bases, Ft. Sam Houston, TX, and the San Antonio Metropolitan Health District. Eleven organizations were positive for Aedes albopictus; the collection of Ae. albopictus at Arnold Air Force Base, TN, is a new record for Coffee County. Ten organizations were positive for Ae. aegypti; 18 were positive for Ae. triseriatus. PMID- 2230793 TI - Robert Charles Wallis. 1929-1989. PMID- 2230794 TI - Physiologic responses of paraplegics and quadriplegics to passive and active leg cycle ergometry. AB - The purposes of this study were three-fold: (a) to determine acute physiologic responses of spinal cord injured (SCI) subjects to peak levels of leg cycle ergometry utilizing functional neuromuscular stimulation (FNS) of paralyzed leg muscles, (b) to determine the relative contributions of passive and active components of FNS cycling to the peak physiologic responses, and (c) to compare these physiologic responses between persons who have quadriplegia and those who have paraplegia. Thirty SCI subjects (17 quadriplegics and 13 paraplegics) performed a discontinuous graded FNS exercise test from rest to fatigue on an ERGYS 1 ergometer. Steady-state physiologic responses were determined by open circuit spirometry, impedance cardiography with ECG, and auscultation. In the combined statistics of both groups, it was noted that peak FNS cycling significantly increased (from rest levels) mean oxygen uptake by 255%, arteriovenous O2 difference VO2 and VE, Q and a-vO2 and VCO by 69%, and stroke volume by 45%, while total peripheral vascular resistance decreased by 43%. Mean peak power output for paraplegics (15 W) was significantly higher than for quadriplegics (9 W), eliciting higher peak levels of pulmonary ventilation and sympathetically mediated hemodynamic responses such as cardiac output, heart rate, and systolic and diastolic arterial blood pressure. Passive cycling without FNS produced no statistically significant increases in physiologic responses above the resting level in either group. PMID- 2230795 TI - Augmentation cystoplasty and closure of the urethra for the destroyed lower urinary tract. AB - Five paraplegic patients with pressure ulceration complicated by incontinence related to fistula formation were treated by deliberate closure of the urethra and augmentation cystoplasty with a continent stoma. This procedure is similar in scope to urinary diversion but preserves a low-pressure reservoir and obviates the use of tubes for drainage of urine. Overall outcome was excellent. Valvular failure occurred in one patient and required revision. The follow-ups range from 1 to 5 years, with a mean of 24 months. One patient developed reservoir calculi as a late complication, necessitating removal with flexible endoscopy via the continent conduit. All patients have preserved normal upper tracts. Augmentation cystoplasty with closure of the urethra is a reasonable procedure in such patients providing for low-pressure urinary storage and permitting secondary or simultaneous plastic surgical procedures on perineal pressure ulceration and osteomyelitis. PMID- 2230796 TI - Don't forget the serratus. AB - Patients quadriplegic at the C6 level may not be considered candidates for independent transfers and weight shifting because of lack of primary shoulder depressors. However, we have observed that some quadriplegics have been able to use the serratus anterior for this latissimus dorsi function. We present an example of this technique, demonstrated by a patient with a complete C6 injury, and compare him with a subject with normal musculature. PMID- 2230797 TI - Authors complimented. Augmentation cystoplasty. PMID- 2230798 TI - Expression of the ganglioside GD3 in human meningiomas is associated with monosomy of chromosome 22. AB - The ganglioside composition of 59 meningiomas has been compared with a molecular genetic analysis of chromosome 22 in the same specimens. Major gangliosides were GM3 (II3NeuAc-LacCer) and/or GD3 [II3(NeuAc)2-LacCer]. In specimens with no or partial deletions of chromosome 22, the GM3 ganglioside predominated, and the mean value for GM3, 61% of total sialic acid, was around four times higher than that for GD3. A loss of chromosome 22, found in 56% of the specimens, was shown to be associated with an increase in the proportion of ganglioside GD3, with the ratio between mean values of GM3 and GD3 being approximately 1:1. Logistic regression revealed that the probability of predicting monosomy of chromosome 22 by the GD3 proportion was 66%. PMID- 2230799 TI - Labeling of retina and optic tectum phospholipids in chickens exposed to light or dark. AB - The labeling of retina ganglion cell and optic tectum phospholipids was determined in chickens given an intraocular injection of 32P and then either exposed to light or maintained in the dark. Significantly higher labeling was found in the optic tectum phospholipids of light-exposed compared with dark maintained animals after 3-24 h of labeling. In the ganglion cells, the labeling of phospholipids increased in dark with respect to light at 15 and 30 min of labeling; from 60 min to 24 h, the labeling of phospholipids was significantly higher in light with respect to dark, even if the precursor pool showed a higher labeling in dark at all times studied. When labeling was allowed to proceed in the dark for 30 min and then half of the animals were exposed to light for 15 min, the labeling of ganglion cell phospholipids of light-exposed animals was significantly higher than those of animals kept in the dark. No individual phospholipid accounted for the differences observed in the labeling of the total phospholipid pool. These results are interpreted as an increase in the biosynthesis of phospholipids in the ganglion cell somas in light with respect to dark. PMID- 2230800 TI - Administration of vigabatrin (gamma-vinyl-gamma-aminobutyric acid) affects the levels of both inhibitory and excitatory amino acids in rat cerebrospinal fluid. AB - The effect of vigabatrin (gamma-vinyl-gamma-aminobutyric acid), a new anticonvulsant drug, on the transmitter amino acids in rat cisternal CSF was studied. CSF was collected through a permanently implanted polyethylene cannula from freely moving rats at 5, 24, 48, and 96 h after administration of 1,000 mg/kg of vigabatrin. The free gamma-aminobutyric acid (GABA) level was elevated maximally (13.5-fold; p less than 0.01) at 24 h after injection. The homocarnosine (GABA-histidine) level also was increased (123%; p less than 0.01) at 24 h after injection, and its concentration remained at the same level for the next 3 days. Glycine and taurine concentrations had increased [31% (p less than 0.05) and 63% (p less than 0.01), respectively] at 5 h after injection. It is interesting that the levels of glutamate and aspartate increased [330% (p less than 0.05) and 421% (p less than 0.01), respectively] at 96 h after injection, the time when the free GABA level had returned to the baseline concentration and the vigabatrin level was 3% of the maximal concentration. The present study indicates that a single dose of vigabatrin in rats elevates levels of both the inhibitory and excitatory amino acids in CSF. However, the temporal profile of observed changes in relation to vigabatrin injection shows that neither the long lasting elevation of GABA content nor the increase in glutamate and aspartate levels correlates with the level of vigabatrin in CSF. These findings suggest that the excitatory mechanisms are also augmented following acute administration of vigabatrin, especially when the content of GABA had decreased to the baseline level and the level of vigabatrin was low. PMID- 2230801 TI - Rapid rise in transcription factor mRNAs in rat brain after electroshock-induced seizures. AB - Recent studies have demonstrated that several transcription factor genes are rapidly activated by neuronal stimulation. For example, we have found that prolonged and repeated seizure activity produced by administration of chemical convulsants induces a rapid and transient increase in mRNA levels of four immediate early genes in rat brain. These genes, zif/268, c-fos, c-jun, and jun B, encode sequence specific DNA binding proteins thought to act as transcription regulatory factors. To ascertain whether a brief electrically induced seizure discharge of the type utilized in clinical electroconvulsive treatment is sufficient to induce a similar genomic response, we have examined the response of these mRNAs in rat brain following single and repeated electroshock-induced seizures. After electroshock, mRNA levels of each of these genes increase within 15 min, and all except c-jun return to near baseline levels within 4 h. Although this response is most prominent in granule cell neurons of the hippocampus, increases are also apparent in neocortex and pyriform cortex. The rapid mRNA response persists in animals receiving a chronic electroshock protocol similar to that used in clinical electroconvulsive therapy. Intrahippocampal infusion of the sodium channel antagonist tetrodotoxin blocks hippocampal mRNA responses without blocking seizures, indicating a role for electrical excitation in the electroshock-induced mRNA response. By contrast, pretreatment with anticonvulsants or selective NMDA antagonists, which reduce seizure intensity and block hindlimb extension, fails to alter mRNA responses, suggesting that seizure induction, rather than spread, is linked to these mRNA responses. Because electroshock induces robust, highly reproducible mRNA responses, it may be useful to study the neuronal genomic response to stimulation. PMID- 2230802 TI - Lipid droplets in Schwann cells during tellurium neuropathy are derived from newly synthesized lipid. AB - Exposure of weanling rats to a diet containing elemental tellurium results in a peripheral neuropathy characterized by segmental demyelination and minimal axonal degeneration. One of the earliest ultrastructural abnormalities in tellurium neuropathy is an increased number of cytoplasmic lipid droplets in myelinating Schwann cells. The pathogenesis of these lipid droplets was investigated using light and electron microscopic autoradiography. Nerve lipids were either "prelabeled" with [3H]acetate via in vivo intraneural injection 3 days before a 2 day exposure to tellurium, or "postlabeled" via in vivo intraneural injection or in vitro incubation with [3H]acetate following a 2-day exposure to tellurium. In the prelabeled nerves, myelin became heavily labeled, but the tellurium-induced cytoplasmic lipid droplets were rarely labeled. In the postlabeled nerves, the tellurium-induced cytoplasmic lipid droplets were the most heavily labeled structures within the nerve. These data indicate that the tellurium-induced lipid droplets in Schwann cells are derived from newly synthesized lipid rather than from the early breakdown and internalization of myelin lipids. The earliest biochemical abnormality observed in tellurium neuropathy is an inhibition of cholesterol synthesis at the squalene epoxidase step. This leads to an accumulation of squalene within the nerve. We conclude that the cytoplasmic lipid droplets in Schwann cells contain this accumulated lipid. PMID- 2230803 TI - Subcellular fractionation of prohormone processing products in the bag cell neurons. AB - Multiple biologically active peptides arising from a common prohormone are sorted into distinct classes of dense core vesicles within the bag cell neurons of Aplysia californica. In this study, pulse-chase analysis, combined with subcellular fractionation on Percoll gradients, are used to define the location of the prohormone processing events within the secretory pathway. Initial cleavage of the prohormone occurs in a light cellular compartment associated with the Golgi apparatus. The amino-terminal processing intermediate then accumulates in a denser compartment containing small dense cores enclosed in membranous sacs, as well as larger immature vesicles. After 4 h, amino-terminal products are found primarily in a much denser compartment which consists of large and small dense core vesicles. These large and small vesicles can be separated from each other using Percoll gradient centrifugation and are found to be enriched in amino- and carboxy-terminal products, respectively. Lastly, membrane association experiments suggest differential binding to membranes, or integral membrane proteins, as a possible mechanism for sorting of amino- and carboxy-terminal products. PMID- 2230804 TI - Characterization and distribution of transferrin receptors in the rat brain. AB - Transferrin receptors were characterized with 125I-ferrotransferrin on membrane fractions prepared from the rodent forebrain. The distribution of transferrin receptors in the rat brain was investigated further by in vitro autoradiography. Saturation binding analysis revealed an apparent single class of sites with a dissociation constant of 2 nM and a binding site density of 15 pmol/g. The Hill coefficient derived from these data was 1.05, indicating the absence of cooperativity and that 125I-ferrotransferrin binds to a single class of sites. Estimates of the kinetically determined KD for forebrain membranes were within the 2-4 nM range, in agreement with the equilibrium measurements. Apotransferrin and ferrotransferrin competitively displaced the binding of 125I ferrotransferrin, while ferritin, albumin, and cytochrome c failed to compete for the binding site. Ceruloplasmin, the copper transport protein, was a weak inhibitor of 125I-ferrotransferrin binding. Autoradiographic localization studies demonstrate a heterogeneous distribution of transferrin receptors in the rat brain. Transferrin receptor densities were markedly elevated over the cerebral cortex and the hippocampus. Moderate to high 125I-ferrotransferrin binding was also apparent throughout areas involved in motor functions, including the caudate putamen, the nucleus accumbens, the substantia nigra, the red nucleus, and the cerebellum. PMID- 2230805 TI - Interleukin-1 hyperproduction by in vitro activated peripheral macrophages from cerebellar mutant mice. AB - Several mutations in mice produce complex patterns of neuronal degeneration of the cerebellum and of its afferent pathways. In the staggerer (sg/sg) mutant, atrophy of the lymphoid organs and immunological abnormalities have been described. To search for a possible link between the neurological and the immune disorders in this mutant, we studied the production by its peripheral macrophages of interleukin-1 (IL-1), which roles in both immune and nervous systems are well established. Suspensions of peritoneal and/or spleen macrophages from mutants and their appropriate controls were stimulated in vitro by lipopolysaccharide. Northern and dot blots, performed with murine IL-1 cDNA probes, revealed a clear cut hyperexpression of IL-1 mRNA in staggerer macrophages. An IL-1 bioassay using the IL-1-responsive D10.G4 cell line also revealed a sixfold increase of IL-1 activity in the macrophage supernatants of staggerer mutant mice. The hyperproduction was found in 3-week to 1-year-old staggerer and also in heterozygous (+/sg) mice. A similar phenomenon existed in cerebellar mutants lurcher, Purkinje cell degeneration (pcd), and to a lesser extent reeler and wobbler, but was absent in the neurological mutants weaver, jimpy, and motor end plate disease (medH). These observations establish that in several point mutations in mice, central nervous degeneration is associated with dysregulation of IL-1 production by peripheral macrophages. PMID- 2230806 TI - Decreased protein kinase C activity during cerebral ischemia and after reperfusion in the adult rat. AB - The possible activation of protein kinase C (PKC) during total cerebral ischemia was investigated in the rat. Translocation of PKC activity from the soluble to the particulate fraction was used as an index of PKC activation. There was a drop in the proportion of particulate PKC activity from 30% for controls to 20% by 30 min of ischemia (p less than 0.01). By 20 min of cardiac arrest, there was a 40% decline of the total cellular PKC activity (p less than 0.01). This was not accompanied by an increase in activator-independent activity, a finding indicating PKC was not being converted to protein kinase M. These data suggest that PKC was not activated during ischemia, but rather that ischemia causes a reduction in cellular PKC activity. Translocation of PKC activity to the particulate fraction was not observed in the cerebral cortex or hippocampus of reperfused brain for up to 6 h of recovery following 11-13 min of total cerebral ischemia. The level of total, soluble, and particulate PKC activity in the cerebral cortex was reduced (p less than 0.05), corresponding to the decrease observed by 15 min of ischemia without reflow. A similar decline in activity was also observed in the hippocampus. No increase in activator-independent activity was observed. These data suggest that PKC was inhibited during cerebral ischemia and that this reduced level of PKC activity was maintained throughout 6 h of recovery. We conclude that pathological activation of PKC was not responsible for the evolution of ischemic brain damage. PMID- 2230807 TI - Purification and characterization of a novel brain-specific 14-kDa protein. AB - A new acidic protein specifically present in the brain was purified to homogeneity from bovine brain. The apparent molecular mass was estimated to be 14 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and 57 kDa by gel filtration, a finding suggesting that it exists as a tetramer under physiological conditions. The protein had a high content of Glu and Pro, and its pI was 4.3. The first six amino acid residues of the protein were Met-Asp-Val-Phe Met-Lys, and the amino terminal was blocked. The distribution of the protein examined by Ouchterlony gel immunodiffusion indicates that it is present specifically in brain, including rat, human, and bovine, but could not be detected in 10 other rat tissues examined. The protein was absent in Purkinje cell bodies, as examined by electron microscopic immunocytochemistry, but was present in nerve terminals that make synapse-like contacts with Purkinje cells and in neurons with dark granules in the globus pallidus of the rat. PMID- 2230808 TI - Volume regulation of nerve terminals. AB - Pinched-off presynaptic nerve terminals (synaptosomes) possess significant regulatory volume increase (RVI) and regulatory volume decrease (RVD) capabilities. Following a swelling induced by a hypotonic challenge, the synaptosomes regulate their volume and adjust it, in 2 min, to within 5% of its initial value (RVD) at an initial rate of -0.77 +/- 0.10%/s (mean +/- SEM). Following a shrinking induced by a hypertonic challenge, the synaptosomes also regulate their volume at an initial rate of 0.18 +/- 0.02%/s (RVI), resulting in a new steady state, reached within 5-10 min, with a synaptosomal volume below the original volume. The omission of Na+ or K+ ions from the extrasynaptosomal medium reduces the initial rate of RVI by 72.5 and 66.5%, respectively. The "loop diuretics" bumetanide and furosemide significantly inhibited the RVI of the synaptosomes. In contrast, ouabain, amiloride, or 4,4'-diisothiocyanatostilbene 2,2'-disulfonic acid did not have any significant effect on RVI parameters. Furthermore, bumetanide-sensitive 86Rb uptake by rat brain synaptosomes was stimulated threefold by a hypertonic perturbation of 30%. Thus we conclude that the RVI of synaptosomes is mainly due to a stimulation of the Na+, K+, Cl- co transport system induced by the synaptosomal shrinking following the hypertonic challenge. PMID- 2230809 TI - Embryonic neural cell adhesion molecule in cerebrospinal fluid of younger children: age-dependent decrease during the first year. AB - Poly-alpha-2,8-N-acetylneuraminic acid (poly-alpha-2,8-NeuAc) is developmentally expressed in neural tissue of higher animals, where it is covalently attached to the neural cell adhesion molecule (NCAM), a large integral membrane glycoprotein mediating cell-cell adhesion during neuronal development. NCAM exists in several molecular forms, of which only embryonic NCAM carries lengthy chains (n greater than 5) of poly-alpha-2,8-NeuAc. Chemically identical poly-alpha-2,8-NeuAc of bacterial origin is an important virulence factor in infections caused by Neisseria meningitidis group B and Escherichia coli K1, the predominant pathogens of bacterial meningitis. A quantitative enzyme-linked immunoassay was developed using monoclonal antibody (MAb) 735, an MAb specifically recognizing poly-alpha 2,8-NeuAc, and applied to CSF specimens from younger children. Poly-alpha-2,8 NeuAc contents were within the range of 20-0.2 micrograms/ml, decreasing from day 1 to day 300. Immunoprecipitation, immunoblot with a rabbit anti-mouse NCAM serum recognizing the protein part of human NCAM by cross-reactivity, affinity enrichment using immobilized MAb 735, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that poly-alpha-2,8-NeuAc in CSF is bound to human NCAM, probably NCAM-120. PMID- 2230810 TI - Purinergic modulation of hippocampal acetylcholine release involves alpha dendrotoxin-sensitive potassium channels. AB - Modulation of acetylcholine (ACh) release from superfused hippocampal slices was examined when the release of ACh was stimulated by exposure of slices to elevated K+ concentration. Evoked release was not sensitive to inhibition by 0.1 microM tetrodotoxin, but it could be inhibited in a dose-dependent manner by a muscarinic agonist (10-100 nM oxotremorine) and a purinergic agonist (10-100 nM 2 chloroadenosine). The alpha-dendrotoxin (100 nM), which selectively blocks voltage-gated inactivating K+ channels in nerve endings, did not affect the release of ACh under resting or depolarized conditions. However, alpha dendrotoxin reduced the 2-chloroadenosine-induced inhibition of release, but did not alter the oxotremorine-induced inhibition. These results suggest that an alpha-dendrotoxin-sensitive K+ channel may be activated as an obligatory step in the modulation of ACh release by presynaptic purinergic receptor activation, but not in the modulation by presynaptic muscarinic receptors. PMID- 2230811 TI - Blood-brain transfer of L-phenylalanine declines after peripheral but not central nervous administration of vasopressin. AB - To determine whether a previously reported effect of vasopressin on blood-brain transfer of leucine extends to other large neutral amino acids, we measured the regional blood-brain transfer of L-phenylalanine with the integral technique. Intravenous co-injection of L-phenylalanine and arginine vasopressin (30 nmol to 10 pmol) resulted in a decrease of the permeability-surface area (PaS) product of phenylalanine of between 11 and 39%. In addition, the peptide elicited a decrease of the cerebral blood flow of between 11 and 56% combined with a drastic decrease of the cardiac output (32-64%) and an elevation of the blood pressure to approximately 150% of control values. However, we found no changes of the cardiac output, the blood pressure, or the PaS product of phenylalanine after microdialysis (30 min, 5 microliters min-1) of arginine vasopressin (15 mumol L 1) into the dorsal hippocampus, but cerebral blood flow was decreased. The results support the hypothesis that arginine vasopressin receptors at the blood brain barrier are involved in the regulation of large neutral amino acid transfer from blood to brain and indicate that these receptors are located at the luminal membrane of the endothelial cells. PMID- 2230812 TI - Evidence for functional activity of up-regulated nicotine binding sites in rat striatal synaptosomes. AB - A number of studies have found that the chronic administration of nicotine causes an increase in the density of nicotinic binding sites in the brain, but it is not known whether these additional binding sites are functionally active receptors. In this study, the effects of 1-week administration of the potent nicotinic agonist, (+)-anatoxin-a (96 nmol/day via osmotic minipumps), was assessed on [3H]nicotine binding and [3H]dopamine uptake and release in rat striatal synaptosomes. Chronic (+)-anatoxin-a treatment resulted in a 32% increase in the Bmax of [3H]nicotine binding in anatoxin-treated animals compared to control. There was a 43% increase in the activity of 3 microM nicotine to release [3H]dopamine from synaptosomes of anatoxin-treated animals, but the release induced by 20 mM K+ depolarization was unaffected. There was no effect of chronic (+)-anatoxin-a treatment on the uptake of [3H]dopamine. A strong positive correlation (r = 0.64) was found between the density of [3H]nicotine binding sites and the nicotine-induced stimulation of [3H]dopamine release in individual animals. These results indicate that (+)-anatoxin-a, like nicotine, produces an up-regulation of nicotine binding sites following chronic administration, and that these additional sites are functional receptors capable of mediating the release of dopamine from striatal synaptosomes. PMID- 2230813 TI - Gangliosides prevent ischemia-induced down-regulation of protein kinase C in fetal rat brain. AB - Complete obstruction of the maternal blood flow to fetal rats at 20 days of gestation for a period of 10 min causes a significant shift of approximately 22% in protein kinase C (PKC) activity from a cytosolic to a membrane-bound form in the fetal brain. This translocation can be entirely reversed without losses in activity by a single intraperitoneal injection into the gravid rat of either a mixture of disialo- and trisialoganglioside [polysialoganglioside (PSG)] or by GM1 (50 mg/kg of body weight) given 3 h before onset of the ischemic episode. Cessation of blood flow for 15 min followed by a reperfusion period of 24 h results in a 47% loss in total PKC activity. This down-regulation can be almost entirely prevented upon intraperitoneal administration of GM1 3 h before, but also during and even 90 min after the onset of ischemia. The PSG mixture is also effective, particularly when given 3 h before the insult. Down-regulation of PKC is accompanied by an increase in a Ca2(+)-phosphatidylserine-independent kinase [protein kinase M (PKM)] activity, which rises from 30 pmol/min/mg of protein in control animals to a maximal value of 83.1 pmol/min/mg of protein after 15 min of ischemia and 6 h of reperfusion. By 24 h, PKM activity is 46.8 pmol/min/mg of protein. Administration of GM1 blocks completely the appearance of PKM, a result suggesting that PKC down-regulation and PKM activity elevation are intimately associated events and that both are regulated by GM1 ganglioside. PMID- 2230814 TI - Nerve growth factor enhances the expression of the cholinergic-specific ganglioside Chol-1 in cocultures of rat septum and hippocampus. AB - Cocultures of septal and hippocampal tissues taken from 6- to 7-day-old rats were maintained in culture for up to 30 days in the presence and absence of nerve growth factor (NGF), and their Chol-1 contents determined at varying time intervals by a modified enzyme-linked immunosorption assay (ELISA). The major brain gangliosides were determined densitometrically after spraying chromatograms with resorcinol reagent. There was little change in the contribution of the major gangliosides to the total ganglioside content of the explants either with time or the presence or absence of NGF, the only exception being an NGF-insensitive fall in the contribution of GM1 to about 60% of its initial value at 20 and 30 days. By contrast, the concentration of Chol-1 expressed either per unit weight of ganglioside sialic acid or protein increased considerably in culture and this increase was enhanced by NGF. The effect of NGF resembles that on other cholinergic markers, choline acetyltransferase and acetylcholinesterase, and may be attributed to an NGF-stimulated hippocampal ingrowth of cholinergic fibres and enhanced survival of cholinergic septal neurons. The Chol-1 concentration finally attained in the presence of NGF and the time course of its increase parallel those previously found in vivo and indicate the potential usefulness of septal hippocampal cocultures for investigating the function of Chol-1. PMID- 2230815 TI - A novel potential metallopeptidase derived from the enkephalinase gene by alternative splicing. AB - Amplification of rat intestine mRNAs was performed by the reverse transcriptase polymerase chain reaction (RT-PCR) using various oligonucleotide primers mainly corresponding to the translated region of the enkephalinase (EC 3.4.24.11, membrane metalloendopeptidase, MME I) gene. In addition to the expected transcript, a shorter one was identified and its sequence indicated that it corresponds to an alternatively spliced mRNA from which exons 5-18 of MME I are deleted. It encodes a deduced 255 amino acid protein, MME II, instead of the 742 amino acid sequence of enkephalinase. The deduced structure of MME II is consistent with its being a membrane-bound, zinc-containing glycoprotein with a modified peptidase activity. MME II mRNA is also expressed, together with MME I mRNA, in brain and thyroid in a tissue-specific manner. PMID- 2230816 TI - Computer predictions of bone remodeling around porous-coated implants. AB - Computer simulations of bone remodeling in response to mechanical stresses can be used to understand normal growth and development of the skeleton or to predict the remodeling of bone in response to prosthetic devices. Using a previously derived bone maintenance theory, a technique for computing bone density distributions was applied to the proximal femur and tibia using two-dimensional, multiple-loading finite element models. The models initially represented solid, homogeneous structures. Using an iterative bone remodeling technique that relates bone apparent density to loading history, the internal distributions of apparent density and elastic modulus for the normal bones were predicted. The finite element models were then modified to represent bones in which porous-coated femoral surface replacements and tibial tray components had been implanted. The same iterative remodeling method was then applied to predict the distribution of bone around these components. The predicted bone density distributions for the natural femur and tibia agree with previously documented normal bone morphology. The predicted bone density distributions around various implanted prostheses were characteristic of the component under investigation and were consistent with clinical and experimental findings of other investigators. In the femoral head, stress shielding occurred underneath the metal surface replacement cup, resulting in lower densities in the femoral head. The addition of a central femoral cup fixation peg caused bone hypertrophy around the peg. In the tibia, the stress concentrations around the pegs also resulted in denser bone, with a concomitant decrease in bone density at more peripheral locations underneath the prosthetic tray. This remodeling technique has the potential to be an important tool in predicting the possible remodeling consequences of new implant design features. PMID- 2230817 TI - Threaded acetabular components for primary and revision total hip arthroplasty. AB - A clinical and radiographic review of 48 total hip arthroplasty patients with threaded acetabular components was undertaken at 24-44 months of follow-up study. Twenty-five patients had primary hip arthroplasties and 23 had revision procedures. Clinical scores revealed good to excellent results in 60% of primary and 30% of revision procedures. Radiographic analysis revealed stable acetabular components in 88% of primary and 61% of revision procedures. Potentially loose acetabular components were noted in 8% of primary and 4.3% of revision procedures and loose acetabular components in 4% of primary and 34.7% of revision procedures. The rate of acetabular component loosening was considered unacceptably high in revision cases and an area of concern in primary cases. Discretionary use of these components is advised. PMID- 2230818 TI - Early loosening of revision hip arthroplasty. A roentgen stereophotogrammetric analysis. AB - The primary migration of 15 and 22 cemented acetabular and femoral prosthetic components was recorded in 23 patients operated because of type I (minimal endosteal bone loss) and type II (thinning of bone, enlargement of femoral canal and acetabulum) mechanical loosening. Roentgen stereophotogrammetric analysis was used to measure the three-dimensional displacements of the center of the acetabulum and the femoral head. All but 1 of the acetabular and 1 of 15 revised femoral stem prostheses migrated within 2 years after the operation, whereas 5 of 7 revised femoral surface arthroplasties were stable. Femoral components with type II loosening migrated, on average, 1.5 mm (range, 0.6-3.0 mm) during the first postoperative year, compared with 0.7 mm (range, 0.3-1.1 mm) in patients with type I loosening (P less than .02). Increased bone loss of the acetabulum (type II), the quality of the bone-cement interface as judged from radiographs, and the presence of perforation of the femoral cortex did not significantly influence the rate of migration in this group. Compared with previously presented studies of cemented primary hip prostheses, cemented revisions seem not only to migrate more frequently but also at a higher rate. Poor primary fixation is probably one important cause of the high frequency of clinical failures in these patients. PMID- 2230819 TI - Cementless total hip arthroplasty with femoral head bone grafting for hip dysplasia. AB - Femoral head bone grafting was required to augment acetabular bone stock in 19 cases of hip dysplasia treated with cementless total hip arthroplasty. All acetabular grafts provided mechanical support for the cementless acetabular component. Radiographic evaluation of the fixation of the femoral components at an average of 3 years after surgery revealed an optimum appearance in all cases. All porous-coated acetabular components remained stable, but only one of six (17%) nonporous threaded acetabular components maintained stability. One threaded acetabular component has been revised for symptomatic loosening. Acetabular graft healing was suspected in 18 of 19 cases (95%). Significant graft resorption was observed only in the cases with unstable threaded acetabular components. The clinical scores were high. Cementless total hip arthroplasty with structural acetabular grafting and porous acetabular components appears to produce satisfactory short-term results. PMID- 2230820 TI - Segmental fracture of the femoral stem of a low-friction arthroplasty. A case report. AB - Fracture of the femoral stem of a cemented hip arthroplasty is a well documented complication. However, double or segmental fracture is extremely rare, with only one other case appearing in the literature. The authors report a second case and discuss its etiology. They stress the importance of prolonged careful review of patients following total hip arthroplasty in order to obviate complications. PMID- 2230821 TI - A comparative study of uncemented tibial components. AB - The effect of tibial component stem and post design on load distribution and on displacements at the component-bone interface was investigated. Four different configurations were tested with a flat component used as a control. Loading conditions included vertical central, vertical offset (eg, varus/valgus), shear and torque. Both artificial and cadaveric bones were used in the study. Pressure sensitive film was used to obtain pressure patterns at the interface. Image processing was then used to quantify the load distribution. For shear and torque, relative motion was seen as a smeared pressure pattern. This was calibrated in terms of microns of displacement as a function of image density. The central stemmed and bladed designs performed better than short-pegged designs, in resistance to offset loading. In shear and torque, short pegs close to the component periphery, or a central stem with blades, produced the least interface displacement. The application of this work to the design of components for both press-fit and cemented application is discussed. PMID- 2230822 TI - Unconstrained knee arthroplasty after patellectomy. AB - The authors report seven cases of unconstrained knee arthroplasty with excision of both cruciate ligaments, after previous patellectomy. Six of these seven cases were completely painfree and function was satisfactory in all cases. The reasons for previously reported pain and instability after total unconstrained knee arthroplasty with excision of the cruciate ligaments and a previous patellectomy are discussed. PMID- 2230823 TI - Patellar resurfacing in total condylar knee arthroplasty. Technique and results. AB - One hundred thirty-two total condylar knee arthroplasties with a 3-8-year follow up period were studied prospectively with particular reference to the patellofemoral joint. All patients had significant patellofemoral disease and underwent primary patellar resurfacing. After operation 96% of patients had little or no pain and 98% had functional improvement. There were seven (5%) complications related to the patellofemoral joint. The importance of careful attention to preparation of the patella, the technique of prosthetic implantation and correct patellar tracking were emphasized. Routine patellar resurfacing proved highly successful with minimal complications. PMID- 2230824 TI - The results of treatment of supracondylar fracture above total knee arthroplasty. AB - This study analyzes the results of treatment of 22 patients with 24 supracondylar femur fractures above a total knee arthroplasty. Ten knees were treated by closed methods utilizing traction and then a cast, 10 knees with immediate open reduction and internal fixation, 2 knees with a custom total knee integrated with a distal femoral allograft, 1 knee with external fixation, and 1 knee with primary arthrodesis. Nine fractures treated by closed means and 5 fractures treated by open reduction and internal fixation healed primarily. Two of the 5 surgical failures healed after replating and bone graft. The 3 failures of surgical therapy were salvaged utilizing custom total knee arthroplasty, 2 of which required integration with a distal femoral allograft. One knee treated with external fixation developed a deep infection necessitating implant removal and arthrodesis. Twelve of the 14 femoral fractures that united primarily healed with the femoral component in varus with respect to the long axis of the anatomic femur. Nine of these 12 implants developed progressive radiolucent lines at the tibial component. Three of these knees have required implant revision due to progressive loosening of the tibial and/or femoral components. The results of this evaluation indicate that fractures above a well-fixed total knee arthroplasty are difficult to manage. If anatomical alignment cannot be achieved by simple closed techniques, then primary open reduction and internal fixation should be considered. However, because of the complexity of the problem, the surgeon should be prepared to perform a primary arthrodesis or revision using custom components with or without a distal femoral allograft. PMID- 2230825 TI - Persistent infection after successful arthrodesis for infected total knee arthroplasty. A report of two cases. AB - Infection in total knee arthroplasty has been reported to range from 1.1% to 12.4%. The literature contains numerous articles on salvage procedures including antibiotic suppression, surgical debridement, resection arthroplasty, arthrodesis, reimplantation, and amputation. Of those knees not reimplantable, a successful arthrodesis is felt by many to give the most predictable long-term results. The majority of literature on arthrodesis for infected total knee arthroplasty concentrates on technical factors and techniques to facilitate fusion. A successful fusion is considered an end point of treatment. PMID- 2230826 TI - A comparison of transfusion requirements after total knee arthroplasty using the Solcotrans autotransfusion system. AB - Twenty-five consecutive total knee arthroplasties were performed with the Solcotrans unit for scavenging postoperative drainage (study group) and were compared with the previous 25 arthroplasties performed without the Solcotrans unit (control group). Mean preoperative hematocrits, estimated blood loss, and fluid replacement for both control and study groups were nearly identical. When the autotransfusion system was not used, 10 patients in the control group required transfusion of a total of 20 units of packed red blood cells, while only two patients utilizing the Solcotrans unit required transfusion of five units of packed red blood cells (P less than .01). The total amount autotransfused in the study group averaged 607.9 mm, and the hematocrit of the scavenged drainage was 29.3%. Samples from all autotransfusions were sent to the microbiology lab for routine culture and were finalized as no growth after 14 days. Serial postoperative hematocrits, platelet counts, prothrombin, partial thromboplastin, blood urea nitrogen, and creatinine values were compared between the two groups. No significant differences were found, and no evidence of coagulopathy, thrombocytopenia or renal dysfunction was found in the study group. PMID- 2230827 TI - Polyglucosan body axonal enlargement increases myelin spiral length but not lamellar number. AB - The area of the unrolled myelin sheet of internodes of myelinated fibers (MF) of peripheral nerve is thought to be determined by axonal caliber and internodal length. We studied the effect of a focal increase of axonal caliber due to the deposition of polyglucosan bodies (PGB), amylopectin-like glucose polymers, on number of myelin lamellae (NL), interlamellar distance (periodicity), and myelin spiral length (MSL) from a sural nerve biopsy specimen of a patient with chronic inflammatory demyelinating polyneuropathy. Axonal area, NL, periodicity, and MSL were estimated within internodes of MF above, at, and below PGB. The axon caliber at the level of the PGB was significantly (P less than 0.002) increased when the PGB was included. At the PGB, NL and their periodicity were not significantly different from those above or below the PGB. The MSL was significantly longer overlying the PGB than it was in the same internode above or below the PGB. Because slippage or stretching of the myelin sheath as well as movement of molecular constituents of myelin is not likely over large distances, localized biosynthesis and assembly of new myelin may explain this increase of MSL. PMID- 2230828 TI - Comparison of aminopeptidase, dipeptidyl aminopeptidase and tripeptidyl aminopeptidase activities in brain tissue from normal and Alzheimer's disease cases. AB - Recent evidence has suggested that Alzheimer's disease may result from an underlying defect of protein catabolism. In an attempt to identify such a defect, we have undertaken the systematic identification and characterization of the proteolytic enzymes responsible in human brain for oligopeptide breakdown via hydrolysis of NH2-terminal residues--the aminopeptidases, dipeptidyl aminopeptidases and tripeptidyl aminopeptidases. The activities of these enzymes were determined following anion exchange chromatographic fractionation of cortical soluble extracts, to prevent interference in the respective assay procedures by the major cortical aminopeptidase. Corresponding enzyme types showed similar levels of activity in soluble extracts of frontal cortex from normal and Alzheimer's disease cases. These data suggest that the characteristic neurodegeneration associated with Alzheimer's disease does not result from altered aminopeptidase, dipeptidyl aminopeptidase or tripeptidyl aminopeptidase activity in cortical tissues of patients with this disorder. PMID- 2230829 TI - Expression of various isoforms of neural cell adhesive molecules and their highly polysialylated counterparts in diseased human muscles. AB - Antibodies directed against neural cell adhesive molecules (NCAM) and in particular a monoclonal antibody recognizing polysialylated isoforms, were used to characterize the expression of these molecules in normal and diseased human muscles. Normal subjects as well as patients with inflammatory, dystrophic and denervating diseases were examined. By immunohistochemistry the main observations were (1) satellite cells expressed the non-sialylated form of NCAMs; (2) regenerative fibers strikingly expressed NCAMs and their sialylated isoforms both on membranes and in the cytoplasm; (3) in denervated muscles, fibers in atrophic groups and some fibers in acute denervation expressed NCAMs on their membrane but not the highly sialylated form; (4) finally, some fibers in myotonic dystrophy and fibers with rimmed vacuoles also expressed NCAMs. Biochemical approaches, using enzymes such as endoglycosidase N and phosphatidylinositol phospholipase C combined with immunoblot analysis allowed visualization of the nature of the expressed isoforms. We have shown that non activated cells, i.e. satellite cells and denervated fibers do not express polysialylated NCAMs. This post translational modification may be only observed in activated or regenerating fibers. This would parallel the sequence of NCAM expression occurring in normal myogenic pathways. PMID- 2230830 TI - Arteriolosclerotic leucoencephalopathy in the elderly and its relation to white matter lesions in Binswanger's disease, multi-infarct encephalopathy and Alzheimer's disease. AB - Arteriolosclerotic leucoencephalopathy in the elderly (ALE) is characterized by white matter lesions associated with atherosclerosis and arteriolosclerosis. Mild lesions are focal and probably represent early status cribosus or incomplete lacunar infarcts. Moderate and severe lesions are diffuse areas of demyelination in the centrum semiovale in which lacunar infarcts are seldom observed. The incidence of ALE in a consecutive necropsy series of 50 cases (mean age 62.6 +/- 13.1 years) was 52%, it was rare in the fourth and fifth decades but increased thereafter to reach a prevalence of 100% at the age of 80 years. Mild lesions occurred in 19 patients and lesions were moderate or severe in 7 (14%). The mean age was higher in this group (74.7 +/- 7.6 years) than in patients with white matter changes as a whole. Dementia occurred only in 3 patients with moderate or severe ALE. These data suggest that (a) ALE is common in old age and is probably the cause of leuko-araiosis in most CT scans in the elderly; (b) ALE may be asymptomatic; (c) the severity of white matter changes may be not related to the severity of neurological deficits; and (d) multiple lacunar infarcts or associated degenerative diseases (i.e., Alzheimer's disease) may be the main cause of dementia in patients with ALE. White matter lesions in ALE, Binswanger's disease, transition areas in multi-infarct encephalopathy (MIE) and Alzheimer's disease (AD) are similar in morphology and are probably the result of a subacute hypoperfusion/hypoxic process. Increased arterial blood pressure is a frequent risk factor in ALE, Binswanger's disease and MIE, whereas congophilic angiopathy of the meningeal and cortical vessels, in addition to mild or moderate arteriolar hyalinosis in the white matter, may play a role in the pathogenesis of incomplete infarctation of the white matter in patients with AD. PMID- 2230831 TI - Potassium channel activity in sarcolemmal vesicles formed from skeletal muscle fibres of normal and dystrophic mice. AB - Sarcolemmal vesicles were produced from adult mouse extensor digitorum longus muscle (EDL) by treating swollen muscle fibres with collagenase. Vesicles formed from dystrophic (C57BL/6J dy/dy) and phenotypically normal animals were patch clamped and the single channel activity was recorded. Three types of K+ channel were observed in excised patches taken from normal and dystrophic muscle. A large conductance (300 pS) Ca2(+)-dependent K+ channel (KCa) was the most frequently observed of the K+ channels in both types of muscle preparation. In a number of patches taken from dystrophic muscle the open probability-voltage relationship for the KCa channel was markedly different from that in normal muscle, suggesting a possible reduction in Ca2+ sensitivity. An ATP-sensitive K+ channel (90 pS) was common to both normal and dystrophic muscle vesicles and was present in a large number of patches. An inwardly rectifying K+ channel (40 pS) was also observed in both types of sarcolemmal vesicles. The properties of all three K+ channels types were broadly consistent with other observations of skeletal muscle K+ channels, though all had higher conductances than had previously been noted in other species. PMID- 2230832 TI - Transferrin receptors in rat central nervous system. An immunocytochemical study. AB - Using an immunocytochemical method we demonstrated the presence of TfR on adult rat neurons, particularly in the cerebral cortex and brain stem. The monoclonal antibody (mab) against rat TfR (clone OX 26) stained neurons of all cortical layers and in the brain stem where the reaction was most evident. Purkinje cells in the cerebellum and scattered neurons in the gray matter of the cervical spinal cord were weakly stained. Choroid plexus cells also reacted with the mab against TfR whereas oligodendrocytes in the cerebral white matter were faintly outlined by the mab. The presence of TfR on endothelial cells of brain capillaries was here confirmed. PMID- 2230833 TI - Quantitative analysis of gait in Parkinson patients: increased variability of stride length. AB - Analysis of the spatio-temporal and kinematic parameters of locomotion recorded in 21 parkinsonian patients compared to 58 normal elderly subjects showed significant differences in all the recorded parameters. However the relationship between these parameters was preserved, as was the basic locomotor pattern. The variability of stride length, more marked in parkinsonian patients, increased as a function of the clinical stages of Hoehn and Yahr. This index could be useful in assessing the course of the disease in patients. PMID- 2230834 TI - Decreased brain pathology in organophosphate-exposed rhesus monkeys following benzodiazepine therapy. AB - Two benzodiazepine compounds, midazolam and diazepam, were administered as adjunctive treatment to soman-exposed rhesus monkeys to evaluate their effects on acute soman intoxication. Monkeys were pretreated orally with pyridostigmine, exposed to soman, and treated i.m. with atropine, pralidoxime chloride (2-PAM), and with midazolam, diazepam or sterile water (control). All monkeys that received the benzodiazepines recovered sooner and exhibited no convulsions. Neuronal degenerative and necrotic lesions were decreased or eliminated in the entorhinal cortex, caudate nucleus, and hippocampus of those animals that received benzodiazepine therapy. These findings support the continued evaluation of drugs with anticonvulsant activity as standard adjunct therapy for soman intoxication. PMID- 2230835 TI - Astrocyte growth stimulation by a soluble factor produced by cerebral endothelial cells in vitro. AB - Conditioned medium from isolated cerebral capillary endothelial cells (ECCM) was found to promote DNA synthesis in astrocytes and pericytes, but not in oligodendrocytes or endothelial cells (EC) in vitro. The astrocyte was the cell of primary interest and the cell tested in the following experiments. The effect of ECCM on astrocytes was concentration and time dependent. The growth factor was released by EC into the medium in a cumulative manner for up to 72 hours. This release was not the result of a nonspecific leakage of an internal store, since the DNA synthetic activity of cell lysates was negligible. The growth factor secretion per cell was higher in sparse than in confluent EC cultures and was partially inhibited by preincubation of EC with interleukin-1. The DNA synthetic activity was due to a peptide, different from basic fibroblast growth factor, transferrin, bovine fibronectin and platelet derived growth factor, with a molecular weight greater than 50,000. The peptide derived from the cerebral capillary EC could be involved in the local signaling between cell types that control new vessel formation in development, in regeneration after brain tissue injury, or in tumor formation. PMID- 2230836 TI - The fate of Schwann cell basement membranes in permanently transected nerves. AB - After peripheral nerve fiber degeneration, Schwann cell basement membranes (SCBM) persist, maintain the columnar orientation of multiplying Schwann cells, and provide pathways for regenerating axons to original target tissue. Despite the putative importance of these functions, there is little quantitative information on SCBM in chronic denervation. The number, integrity, shape, and size of SCBM were evaluated in transverse electron micrographs of peroneal nerves of groups of mice at various times after permanent sciatic nerve transection. With increasing time after transection, the SCBM fragment, the fragments become shorter, dispersed throughout the endoneurium and partially disappear. The discontinuity, dispersion, and partial disappearance of SCBM, which worsens with time after nerve transection, alters the scaffold by which neurites grow back to formerly innervated or appropriate target tissue. Without reaching appropriate target tissue, regenerating fibers may fail to develop or undergo retrograde atrophy and degeneration. The progressive changes of the SCBM may contribute to the demonstrated poor regeneration when nerve reconnection is delayed, or when proximal nerves are reconnected, so that much time may elapse before neurites grow back to distal nerve. PMID- 2230837 TI - Central nervous system involvement in nephropathic cystinosis. AB - Nephropathic cystinosis, an autosomal recessive lysosomal storage disorder due to impaired cystine transport, causes damage to multiple organs that results in end stage renal disease, hypothyroidism, and retinopathy, usually in childhood. Dialysis and renal transplantation now frequently enable patients with cystinosis to live into adulthood. Examinations at autopsy of a 28-year-old man who died of complications of this disease showed deposits of cystine crystals in multiple organs. There was severe cerebral involvement with multifocal cystic necrosis, dystrophic calcification, spongy change, and vacuolization that had produced profound neurologic deficits. Electron microscopy of the brain documented cytoplasmic deposition of cystine crystals in membrane bound vacuoles within the cytoplasm of pericytes and within parenchymal cells of the white matter. While affected patients who have received renal transplants may no longer die from renal failure, serious, potentially life-threatening, neurologic complications of this disorder may supervene. PMID- 2230838 TI - Morphologic and functional alterations in aging rat muscle. AB - To understand better the causes of reduced contractile force in aging skeletal muscle, we performed a physiologic and morphologic analysis of plantaris muscle in old rats. The peak twitch tension (Fmax) and rates of force development and relaxation were significantly lower in old (24 months old) rats than in young (six month old) rats. In teased muscle fiber preparations, there was a 5% reduction in the mean number of fibers in the aging plantaris muscle. Histologically, a net loss of fibers occurred only in the muscle belly. Histochemically, fewer Type I fibers were seen in the belly and proximal regions, whereas distally fewer Type IIa fibers were seen. The loss of Types I and IIa oxidative fibers suggested a conservation of fast-twitch Type IIb fibers in a fast-twitch muscle. The relatively small loss of muscle fibers does not explain the large decline in muscle contractile performance which, despite established doctrine, was independent of muscle mass, fiber number or size, or number of fast twitch fibers. The reduced force production in aging rat muscle appears to be due to a defect in excitation, contraction performance or metabolic activity, rather than a purely anatomical abnormality of muscle. PMID- 2230839 TI - A distinctive triad of malformations of the central nervous system in the Meckel Gruber syndrome. AB - A distinct triad of central nervous system (CNS) malformations (prosencephalic dysgenesis, occipital exencephalocele and rhombic roof dysgenesis) was present in seven cases of the Meckel-Gruber syndrome examined at autopsy. We compared our findings with those previously described. Microcephaly, sloping forehead, posterior occipital exencephalocele, cerebellar hypoplasia, Chiari malformation, hydrocephalus, polymicrogyria, arhinencephaly, holoprosencephaly and anencephaly constituted a broad spectrum of the reported CNS anomalies. Few reports contained a comprehensive description of the observed CNS malformations. In those reports, and in our cases, features of prosencephalic dysgenesis included agenesis of olfactory bulbs and tracts (arhinencephaly), hypoplasia of optic nerves and chiasm, agenesis of corpus callosum, fused thalami or complete holoprosencephaly. The occipital encephalocele has consisted of a displacement of rhombic roof elements, including caudal third ventricle, cerebellar vermis and fourth ventricle, extruded through an enlarged posterior fontanelle rather than through an occipital cranium bifidum and is thus more precisely labeled an exencephalocele. Different degrees of dysgenesis of posterior fossa structures, described by some as a variant of Dandy-Walker cyst with features of a Chiari malformation, were often associated with this occipital exencephalocele. This pattern of CNS anomalies represents a triad of malformations probably associated with defective ventral induction of the developing CNS by the prechordal mesoderm. PMID- 2230840 TI - Genetic spongiform encephalopathies. PMID- 2230841 TI - Dexamethasone increases plasma levels of albendazole. AB - Therapy of neurocysticercosis with cysticidal drugs is frequently complicated by the exacerbation of symptoms that follows the inflammation triggered by the acute destruction of cysticerci. Treatment of such adverse reactions with dexamethasone is highly effective. However, it has been shown that dexamethasone lowers the plasma levels of praziquantel, thus reducing its cysticidal efficacy. We measured plasma levels of albendazole, another strong cysticidal drug, when dexamethasone was given simultaneously. We found that dexamethasone increased the plasma levels of albendazole by about 50% (P less than 0.002); hence, it seems that cysticercosis and the ensuing inflammation can be treated simultaneously with albendazole and dexamethasone without diminishing the efficacy of the cysticidal drug. PMID- 2230842 TI - Electroencephalographic activity related to palatal myoclonus in REM sleep. AB - Polysomnography, including electroencephalography, electromyography and electro oculography was performed in three patients with palatal myoclonus (PM). The amplitude of the myoclonus decreased during sleep. The frequency did not change during non-REM sleep, but increased during REM sleep in two patients. Ocular myoclonus synchronized with PM disappeared during deep sleep stages in two patients and reappeared during REM sleep in one of them. In the other patient, ocular myoclonus was noted only in REM sleep, being absent even when the patient was awake. All patients showed episodic EEG activities synchronous with myoclonic jerks only in REM sleep. These episodes were noted 5-15 times throughout the night, and each episode lasting for 1-7 s. They were negative or positive waves of saw-tooth appearance which were distributed predominantly in the central region. During the episodes, the frequency of myoclonic jerks increased in two patients. Although it is known that REM sleep influences PM and ocular myoclonus, this is the first report demonstrating the electroencephalographic activity associated with PM. PMID- 2230843 TI - Resistance to ischaemia of small afferent nerve fibres in diabetes mellitus. AB - Thermal thresholds were measured in the left forearms of 26 healthy subjects and 10 patients with diabetes mellitus during ischaemic compression block. During the period when ischaemic block of large fibres caused paraesthesia and loss of touch sensation, the cold threshold rose in normals. The cold threshold was less clearly elevated and the warm perception remained unaltered by ischaemia in diabetics. These results show that not only large afferent and efferent nerve fibres but also thinly myelinated A delta and unmyelinated C fibres are resistant to ischaemia in the diabetic nerve. PMID- 2230844 TI - Headaches and multiple sclerosis: a clinical study and review of the literature. AB - Whether multiple sclerosis (MS) can cause headaches is controversial. To clarify the association between headaches and MS we prospectively analyzed 104 consecutive MS patients using detailed headache evaluations. Fifty-four patients (52%) reported headaches, compared with 5 of 35 (14%) patients initially suspected to have MS but subsequently proven to have other disorders, and 18 of 100 (18%) matched general neurology patients. The MS patients had tension headaches or vascular headaches of the migraine type; there was no distinctive "MS headache." Seven of these patients had headaches with their first MS symptoms, but in only one did headaches recur with disease activity. Headaches did not correlate with any clinical features of MS. We conclude that an association between headaches and MS may exist. PMID- 2230845 TI - Serial studies of evoked potentials and circulating lymphocyte subsets for multiple sclerosis: attempts to monitor progress. AB - A concurrent change in evoked potential measurements and quantitation of circulating T-suppressor (CD8) lymphocyte subpopulations might indicate increased subclinical disease activity. Eight untreated patients with clinically definite multiple sclerosis were monitored monthly for changes in the numbers of cells positive for CD8 markers, and hence in the ratio of CD4: CD8 positive cells. Such changes were found not to be associated with changes in evoked potentials or clinical status. PMID- 2230846 TI - Fatal or severely disabling cerebral infarction during hospitalization for stroke or transient ischemic attack. AB - Six (1%) of 578 patients admitted for cerebral infarction or transient ischemic attack (TIA) suffered a fatal or severely disabling in-hospital cerebral infarction following a period of stabilization or improvement lasting more than 1 day. These infarctions were characterized by the sudden onset of stupor or coma and subsequent development of transtentorial herniation due to carotid or middle cerebral artery territory infarction, or widespread brain-stem infarction due to basilar occlusion. Only one patient survived. Four patients had large-vessel disease documented by Doppler, angiography, or at autopsy. Each of these six infarcts occurred during the morning hours, 4-9 days after the initial event, 3-8 days after initiation of intravenous heparin, and within 4-8 h after intravenous heparin had been discontinued. No coagulation abnormalities were documented. We believe that these cases indicate that among patients admitted for cerebral infarction or TIA, fatal or severely disabling in-hospital cerebral infarction after a period of stabilization or improvement may occur in patients having an initially mild to moderate clinical deficit, that those suffering large artery disease may be at greater risk, and that there may be a relationship between heparin withdrawal and cerebral infarction in some patients. PMID- 2230847 TI - "Quadriceps myopathy": a clinical variant form of Becker muscular dystrophy. AB - A 26-year-old male with "quadriceps myopathy" is presented. He had a family history and only the bilateral quadriceps were wasted, without symptomatic weakness. The specimen of the muscle biopsy showed typical myopathic features without inflammatory reactions. The patchy defect of muscular dystrophin was proved by immunohistochemical study. Dystrophin analysis revealed abnormal 380 kDa dystrophin. Gene deletion was proved at exon 45-48 of Xp21 without frameshift. This case was considered to be a clinical variant form of Becker muscular dystrophy. PMID- 2230848 TI - Unusual blink reflex with four components in a patient with periodic ataxia. AB - Characteristic findings in blink reflex are reported in a 55-year-old female with periodic ataxia. The blink reflexes on the side ipsilateral to the stimulation consisted of four components with latencies of 11, 21, 35 and 47 ms, instead of the usual two components seen in normal subjects. On the contralateral side, the last three components were also present. The second component was different from the normal R2 response in that its latency was shorter than normal and it did not habituate by stimulation at a rate of 10 Hz. In addition, it was more affected by diazepam than the third or fourth components. It is considered that R2 may have consisted of three components and that a shorter latency of the second component could be explained by facilitation. PMID- 2230849 TI - Cardiac transplantation in female Emery-Dreifuss muscular dystrophy. AB - A young woman with humeroperoneal muscular dystrophy and contractures received a heart transplant for a severe dilated cardiomyopathy. Cardiac histopathology consisted of myocyte hypertrophy, interstitial fibrosis, and nuclear hyperchromaticity without mitochondrial abnormalities. Myopathy and heart disease were not clinically evident in her family, although three relatives had unexplained shortened Achilles tendons without weakness. Tendon contractures may be a partial expression of this myopathic disorder, suggesting an autosomal dominant inheritance with variable penetrance. A muscular dystrophy clinically similar to that of the Emery-Dreifuss (EDMD) type can thus occur in women. Rather than the cardiac arrhythmias typical of EDMD, a dilated cardiomyopathy may occur and present with severe congestive heart failure. This is the first report of cardiac transplantation in such a case. PMID- 2230850 TI - Treatment of chronic relapsing inflammatory demyelinating polyneuropathy by cyclosporin A and plasma exchange. A case report. AB - A patient with chronic relapsing inflammatory demyelinating polyneuropathy was successfully treated with plasma exchanges and cyclosporin A (CsA). Dynamometric measurements of hand force during the time of CsA treatment showed a highly significant correlation between hand force and CsA blood levels. The largest influence of CsA on hand force occurred 11-13 days after CsA uptake. PMID- 2230851 TI - Alcohol-dependent unilateral vestibular impairment persisting after a closed head injury. AB - A 20-year-old man suffered a closed head injury followed by symptoms of right sided labyrinthine concussion with complete clinical recovery within 3 weeks. Episodic vertigo and ataxic gait occurred after the ingestion of small amounts of alcohol over the next 2 years. Electro-oculography revealed a right-sided peripheral type vestibular lesion, only after taking alcohol. This was interpreted as an alcohol-induced impairment of central compensation following an incomplete recovery from right-sided labyrinthine trauma. PMID- 2230852 TI - Livedo reticularis and dementia. PMID- 2230853 TI - Neurobiological findings in a case of Gilles de la Tourette's syndrome. PMID- 2230854 TI - Auscultatory mean blood pressure. AB - This study examined the relationship between direct mean arterial blood pressure and cuff pressure for the maximum acoustic index calculated from the Korotkoff sounds in the dog. The acoustic index was computed by summing the squares of amplitudes in each Korotkoff sound complex, thereby providing a measure of acoustic energy content. Mean arterial pressure was compared with cuff pressure for the maximum acoustic index. Ten mongrel dogs were fitted with appropriately sized blood-pressure cuffs containing a microphone mounted inside the bladder and positioned over the brachial artery. The Korotkoff sounds, cuff pressure, and direct arterial pressure were recorded over a range of mean arterial pressures (23 to 155 mm Hg), achieved by manipulating the depth of anesthesia with halothane. It was found that cuff pressure at the maximum acoustic index overestimated mean arterial blood pressure by a mean of 14% (range, -8 to +30%). PMID- 2230855 TI - Placement of esophageal stethoscope by acoustic criteria does not consistently yield an optimal location for the monitoring of core temperature. AB - The esophageal stethoscope has evolved into a device for both acoustic and core temperature monitoring. To test whether routine placement according to acoustic criteria results in placement of the core temperature sensor in the region of contiguity between the esophagus and the heart, we determined the depth of placement electrocardiographically. All patients were undergoing nonthoracic elective operations requiring general anesthesia and tracheal intubation. First, we established that different observers selected the same esophageal depth within +/- 1 cm electrocardiographically, using the criterion of a symmetric biphasic P wave of maximal amplitude (7 patients). Then, in 30 more patients, we compared routine acoustic placements with the depths of the maximal-amplitude biphasic P wave. Stethoscopes placed according to acoustic criteria were within +/- 3 cm of P-wave depths in 15 of 30 patients. In the remaining patients, measured discrepancies ranged up to 13.5 cm. We conclude that the prevailing stethoscope design, with a thermistor at the tip, below the acoustic window, does not ensure placement of the thermistor within the optimal region for monitoring of core temperature. A modification in design that would take advantage of the reliability of electrocardiographic positioning is suggested. PMID- 2230856 TI - Observer reliability in detecting surreptitious random occlusions of the monaural esophageal stethoscope. AB - The esophageal stethoscope is used often during anesthesia to monitor ventilation and cardiac function. Deficiencies in observer vigilance may limit the effectiveness of this monitoring instrument. The aim of this study was to determine how long it took for an observer to detect a surreptitiously occluded monaural esophageal stethoscope in the setting of clinical anesthesia. During routine anesthesia, where an esophageal stethoscope was in use, a computer-guided device would artificially, silently, and at random time intervals, occlude the stethoscope tubing. Personnel using the stethoscope noted when they perceived the absence of stethoscope sounds. We studied 320 stethoscope occlusions in 32 patients. The time between stethoscope occlusion and detection was 34 +/- 59 seconds (mean +/- SD). Eighty-seven percent of detections were made in less than 60 seconds. However, 13% of detections were delayed for more than 60 seconds, and 2.3% for more than 240 seconds. While anesthesia personnel using an esophageal stethoscope could detect most stethoscope occlusions, failure to appreciate such episodes occurred in a small but significant number of cases. This suggests that the esophageal stethoscope has some definite limitations as a continuous monitor and that other monitoring techniques, such as oximetry, capnography, and ventilator disconnect alarms, as well as visual/tactile inspection of the patient, should be used as well. PMID- 2230857 TI - Rib cage and abdominal piezoelectric film belts to measure ventilatory airflow. AB - Piezoelectric film-based respiratory belts are described and tested. To the extent that a two-degree of freedom model consisting of rib cage and abdominal motion is able to assist in quantifying ventilation, the piezoelectric belts can monitor flow in a manner analogous to the monitoring of volume with two magnetometer pairs or two respiratory inductive plethysmograph belts. The piezoelectric belts are shown to measure flow linearly when compared with a screen pneumotachometer to a flow of at least 2.6 L/s. There is no phase shift between the peak flow of belts and the pneumotachometer up to a frequency of at least 9.2 Hz. During normal ventilation, 68 and 95% of the peak flows measured with the belts fall within +/- 10 and 20%, respectively, of the flows measured with a screen pneumotachometer. PMID- 2230859 TI - Recognition accuracy with a voice-recognition system designed for anesthesia record keeping. AB - We tested on three occasions, with anesthetists as subjects, the accuracy of two voice-recognition systems designed for anesthetic record keeping. Initially, a prototype system was tested (10 subjects); several years later the resulting commercial system was tested in a quiet environment (11 subjects) and in noisy operating rooms (10 subjects). For each test an anesthetist first trained the system to recognize his or her voice by reading aloud a list of common anesthetic terms. To determine recognition accuracy, the percentage of words recognized correctly by the computer, each subject repeated the vocabulary words ten times. Although accuracy was similar during the three tests, it was slightly higher with the laboratory test (mean percent of words recognized correctly, 96.5%; range of accuracy for individual anesthetists, 91.6 to 98.8%) than with the prototype test (95.9%; range, 89.1 to 99.6%). Accuracy was lowest with the operating room test (95.3%; range, 87.8 to 98.4%). Twenty-four words caused particular difficulty during the laboratory test and were eliminated from the vocabulary of the subsequent operating room test. Omitting these 24 words from the laboratory vocabulary list allowed a more nearly direct comparison with the results from the operating room list; recognition accuracy improved in the former to 97.5% (range, 92.1 to 98.9%). Two anesthetists--one each from the laboratory and operating room tests--performed poorly, and eliminating their scores changed the respective overall scores to 98.2% (range, 96.7 to 98.9%) and 96.5% (range, 94.3 to 98.4%). Thus, the corrected difference between the laboratory accuracy and the operating room accuracy was 1.7%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230858 TI - Accuracy of four indirect methods of blood pressure measurement, with hemodynamic correlations. AB - In 38 adults undergoing cardiac surgery, 4 indirect blood pressure techniques were compared with brachial arterial blood pressure at predetermined intervals before and after cardiopulmonary bypass. Indirect blood pressure measurement techniques included automated oscillometry, manual auscultation, visual onset of oscillation (flicker) and return-to-flow methods. Hemodynamic measurements or calculations included heart rate, cardiac index, stroke volume index, and systemic vascular resistance index. Indirect and intraarterial blood pressure values were compared by simple linear regression by patient and measurement period. Measurement errors (arterial minus indirect blood pressure) were calculated, and stepwise regression assessed the relationship between measurement error and heart rate, cardiac index, stroke volume index, and systemic vascular resistance index. Indirect to intraarterial blood pressure correlation coefficients varied over time, with the strongest correlations often occurring at the first and last measurement periods (preinduction and 60 minutes after cardiopulmonary bypass), particularly for systolic blood pressure. Within-patient correlations between indirect and arterial blood pressure varied widely--they were consistently high or low in some patients. In other patients, correlations were especially weak with a particular indirect blood pressure method for systolic, mean, or diastolic blood pressure; in some cases indirect blood pressure was inadequate for clinical diagnosis of acute blood pressure changes or trends. The mean correlations between indirect and direct blood pressure values were, for systolic blood pressure: 0.69 for oscillometry, 0.77 for auscultation, 0.73 for flicker, and 0.74 for return-to-flow; for mean blood pressure: 0.70 for oscillometry and 0.73 for auscultation; and for diastolic blood pressure: 0.73 for oscillometry and 0.69 for auscultation. The mean measurement errors (arterial minus indirect values) for the individual indirect blood pressure methods were, for systolic: 0 mm Hg for oscillometry, 9 mm Hg for auscultation, -5 mm Hg for flicker, 7 mm Hg for return-to-flow; for mean: -6 mm Hg for oscillometry, and -3 mm Hg for auscultation; and for diastolic: -9 mm Hg for oscillometry and -8 mm Hg for auscultation. Mean measurement error for systolic blood pressure was thus least with automated oscillometry and greatest with manual auscultation, while standard deviations ranging from 9 to 15 mm Hg confirmed the highly variable nature of single indirect blood pressure measurements. Except for oscillometric diastolic blood pressure, a combination of systemic hemodynamics (heart rate, stroke volume index, systemic vascular resistance index, and cardiac index) correlated with each indirect blood pressure measurement error, which suggests that particular numeric ranges of these variables minimize measurement error.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230860 TI - Pressure measurement artifact with analog-to-digital conversion. AB - Pressure was transduced with the use of a fluid-filled catheter and standard medical monitoring equipment. When the signal was sampled at 200 Hz with an analog-to-digital converter, an artifact was observed. The 3.5-Hz artifact had an amplitude of 0.3 to 0.9 mm Hg and was caused by aliasing of a noise contaminant from the 2,403.5-Hz electrical excitation signal of the transducer. The artifact was completely eliminated with a 100-Hz low-pass filter. Electrical filtering is necessary for accurate acquisition of pressure measurements with analog-to digital conversion, even when the sampling rate satisfies the Nyquist criterion for the frequency response of the mechanical system. Although the impact of the artifact is small in the clinical area, it is important under some research circumstances. PMID- 2230861 TI - Continuous measurement of cardiac output with the use of stochastic system identification techniques. AB - The limitations of developing a technique to measure cardiac output continuously are given. Logical explanations are provided for the economic, technical, and physiologic benefits of a stochastic system identification technique for measuring cardiac output. Heat is supplied by a catheter-mounted filament driven according to a pseudorandom binary sequence. Volumetric fluid flow is derived by a cross-correlation algorithm written in the C language. In vitro validation is performed with water in a flow bench. The computed flow (y) compared with the in line-measured flow (x) yields the linear regression y = 1.024x - 0.157 (r = 0.99). The average coefficient of variation is less than 2% over a volumetric fluid flow range of 2 to 10 L/min. PMID- 2230862 TI - Will we see automated record keeping systems in common use in anesthesia during our lifetime? The automated anesthetic record is inevitable and valuable. AB - The automated anesthetic record is inevitable for at least three reasons: First, much of the information is in electronic form. Second, all the necessary tools for transferring this information into a computer and hence onto a piece of paper are already available. Third, the need for an improvement over the current way of keeping records is widely recognized. Manual records are often inaccurate, biased, incomplete, and illegible, and they divert attention from more important tasks of the anesthetist. Although automated record keeping will not produce perfection, it will improve the situation enough to justify the effort. PMID- 2230863 TI - Will we see automated record keeping systems in common use in anesthesia during our lifetime? The automated anesthetic record will not automatically solve problems in record keeping. AB - The proponents of automated anesthetic records list the ostensibly logical reasons for them and then claim that automated records will make everything better. The logic goes as follows: (1) It is good to have accurate records because accurate records (a) make clinical decision making more effective and improve patient safety, (b) provide better defense against frivolous lawsuits, and (c) enable more astute medical policy decisions based on improved retrospective case reviews; (2) automatic record-keeping systems will give more nearly accurate records; (3) therefore, quality of care will improve if we acquire automatic record-keeping systems. This logic fails on several counts, which are detailed in this essay. Having said all this, however, I do believe that automated record systems will be implemented and they will be extremely useful, both for the patient and for those who care for the patient. However, we must exercise great care in their design and implementation, lest they wind up doing more harm than good. PMID- 2230864 TI - The present and future medicolegal importance of record keeping in anesthesia and intensive care: the case for automation. PMID- 2230865 TI - Spinal cord ischemia and motor evoked potentials. PMID- 2230866 TI - Who should pay for clinical research? PMID- 2230867 TI - Prognostic value of c-myc proto-oncogene overexpression in early invasive carcinoma of the cervix. AB - The prognostic effect of c-myc oncogene overexpression was assessed in a multivariate analysis of 93 patients with invasive carcinoma of the cervix, stage Ib, IIa, and IIb proximal. The treatment was based on the association of brachytherapy-colpohysterectomy and lymphadenectomy. Analysis of c-myc gene expression was done using Northern and slot blot hybridization techniques. Overexpression of c-myc (ie, levels at least three times the mean observed in normal tissues) was present in 33% of the tumors. The proportion of carcinomas with c-myc overexpression significantly increased with the size of the primary tumor (P = .04). No relationship was found between c-myc overexpression and the other clinical and histologic parameters, including the nodal status. The relative risk of relapse (overall, pelvic failure, distant metastases) was analyzed in a Cox's proportional hazards model. Three factors were significantly related to the risk of overall relapse when the multivariate analysis was performed, namely, the tumor size, the nodal status, and c-myc expression. A combination of c-myc expression and the nodal status provided a very accurate indication of the risk of relapse. Indeed, patients with negative nodes had a 3 year disease-free survival rate of 93% (95% confidence interval [Cl], 79% to 98%) when c-myc was expressed at a normal level, whereas this rate was only 51% (95% Cl, 26% to 63%) when c-myc was overexpressed (log-rank test, P = .02). In addition, in the subgroup of patients with positive nodes, this rate was 44% (95% Cl, 25% to 77%) and 15% (95% Cl, 4% to 49%) when c-myc gene was expressed at normal level, or overexpressed, respectively. Finally, c-myc gene overexpression was, in the multivariate analysis, the first factor selected by the model regarding the risk of distant metastases. PMID- 2230868 TI - High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association. AB - One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials. PMID- 2230869 TI - Epirubicin cardiotoxicity: a study of 135 patients with advanced breast cancer. AB - The cardiotoxicity of epirubicin (EPI) was evaluated clinically, radiologically, with ECG, and with multiple ECG-gated radionuclide determination of the left ventricular ejection fraction (LVEF) during rest in 135 patients with advanced breast cancer. The EPI doses were 60 mg/m2 on days 1 and 8 every 4 weeks or 45 mg/m2 plus vindesine 3 mg/m2 on the same schedule. The median cumulative dose of EPI was 500 mg/m2 (range, 47 to 1,563). Eight of the 135 patients developed congestive heart failure (CHF). Of 67 patients treated with EPI less than 500 mg/m2, none developed CHF. Among 48 patients treated with doses between 500 and 1,000 mg/m2, one had CHF (2%; 95% confidence limits, 0.1 to 11.1). Among 20 patients who received EPI from 1,000 to 1,563 mg/m2, seven developed CHF (35%; 95% confidence limits, 15.4 to 59.2). Four patients died due to cardiotoxicity. The risk of EPI cardiotoxicity at the present schedule is considerable at doses above 1,000 mg/m2. At doses between 500 and 1,000 mg/m2 the risk of CHF decreases, and at doses below 500 mg/m2, it is negligible. For all patients, the prevalence of CHF was 6% and the sensitivity of LVEF high (95%), mainly due to the low incidence of CHF. Among the 20 patients who received EPI at more than 1,000 mg/m2, the prevalence of CHF was 35% and the sensitivity only 64%. The specificity was maximally 62%. Our results suggest that LVEF is of no value as a predictor for CHF. PMID- 2230871 TI - Long-term sequelae of conservative treatment by surgery, brachytherapy, and chemotherapy for vulval and vaginal rhabdomyosarcoma in children. AB - Between 1970 and 1978, 17 girls with rhabdomyosarcoma (RMS) of the vulva or vagina were treated at the Institut Gustave-Roussy (IGR) by conservative treatment including surgery, brachytherapy, and chemotherapy. Twelve pubescent or postpubescent girls were studied for long-term sequelae. Eleven of 12 patients have had a normal puberty, two have a total of three healthy children, 11 have normal menses, and 10 normal menarche (one after hormonal replacement). Only one patient underwent hysterectomy following low-dose brachytherapy. Five girls have no vaginal complications, and three are sexually active. Three have had minimal vaginal sequelae, which required surgical correction to permit sexual intercourse. Four girls sustained serious sequelae (colorectal, vaginal, urethral, and ureteral stenosis). These sequelae, secondary to irradiation, are potentially avoidable in the future given the current advances in brachytherapy and improvements in dosimetry. This conservative treatment is useful and appropriate for girls with RMS of vulvar or vaginal origin when complete remission cannot be obtained with chemotherapy and partial colpectomy. PMID- 2230870 TI - Acute renal dysfunction during interleukin-2 treatment: suggestion of an intrinsic renal lesion. AB - Adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has been effective in treating some advanced malignancies in animals and humans. One complication of this treatment is a reversible, oliguric, acute renal failure, which has been ascribed to renal hypoperfusion and resultant prerenal azotemia. We serially studied renal function in 10 patients receiving high-dose regimens of recombinant interleukin-2 (rIL-2) to attempt to delineate further the nature of the renal dysfunction caused by IL-2 treatment. Renal plasma flow was computed from iodine 131 (I-131 Hippuran; Mediphysics, Paramus, NJ) orthoiodohippurate, excretion curves, and glomerular filtration rate (GFR) was determined by creatinine clearance. Studies done prior to and on day 4 of treatment showed that GFR fell in nine of 10 patients, with a mean decrease of 43% +/- 8%, and renal plasma flow fell in five of the 10 patients with a mean decrease of 5% +/- 10%. The average pretherapy filtration fraction was calculated to be 23% +/- 1% and after 4 days of treatment, decreased to a mean value of 15 +/- 2%. The BUN to creatinine ratio also declined in all patients. These findings collectively suggest that IL-2 nephrotoxicity may result from an intrarenal defect in addition to the previously described prerenal azotemia. Additionally, radionuclide studies of renal function are a reliable and reproducible noninvasive method of assessing these changes in renal function. PMID- 2230872 TI - Questionable role of CNS radioprophylaxis in the therapeutic management of childhood rhabdomyosarcoma with meningeal extension. AB - A series of 15 consecutive children with head and neck nonorbital rhabdomyosarcoma (RMSA) with meningeal extension were prospectively treated with chemotherapy consisting of Adriamycin (doxorubicin; Adria Laboratory, Columbus, OH) (ADM), vincristine (VCR), cyclophosphamide (CPM), and dactinomycin (DACT) followed by radiotherapy (60 Gy) to the primary tumor volume, along with intrathecal methotrexate (IT MTX). Thirteen of 15 responded to preradiation chemotherapy. Four of 13 relapsed. Relapse occurred at the level of the primary tumor in three of four. The 3-year progression-free survival (PFS) was 59%, similar to that achieved in a previous series treated with a comparable therapeutic approach that also included whole-brain radiotherapy as a prophylaxis of possible occult meningeal seeding. It is concluded that CNS prophylaxis with radiotherapy is questionable in the management of childhood RMSA with meningeal extension. PMID- 2230873 TI - Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients. AB - We treated 64 patients with metastatic melanoma using a melanoma vaccine preceded by low-dose cyclophosphamide (CY), and monitored immunologic effects and antitumor activity. On day 0, the patients were given CY 300 mg/m2 intravenously. Three days later, they were injected intradermally with vaccine consisting of 10 to 25 x 10(6) autologous, enzymatically dissociated, cryopreserved, irradiated (25 Gy) tumor cells mixed with bacillus Calmette-Guerin (BCG). This treatment sequence was repeated every 28 days. Of 40 assessable patients with measurable metastases, five had responses, four complete and one partial, with a median duration of 10 months (7 to 84+ months). In six additional patients, we observed an antitumor response that seems to be peculiar to this vaccine therapy: the regression of metastatic lesions that appeared after the immunotherapy was begun. Delayed-type hypersensitivity (DTH) to autologous, mechanically dissociated melanoma cells that had not been exposed to extraneous antigens, such as enzymes or fetal calf serum, increased significantly following immunotherapy (day 0 v day 49, P less than .001; day 0 v day 161, P less than .001; day 0 v day 217, P = .021). Antitumor responses to the vaccine were strongly associated with DTH, as indicated by three observations: (1) eight of 10 patients who exhibited tumor regression had positive DTH, (2) in postsurgical adjuvant patients, there was a highly significant linear relationship (P less than .001) between the intensity of DTH to autologous melanoma cells and the time to recurrence of tumor, and (3) nine patients who developed DTH to the autologous melanoma cells in their original vaccine developed new metastases that failed to elicit DTH or elicited a much smaller response. In three cases, we were able to excise regressing tumors for histologic examination; such tumors were characterized by an intense infiltration of lymphocytes. This demonstration that an immune response to melanoma-associated antigens can be elicited in cancer-bearing patients provides some basis for optimism about the prospects for developing active immunotherapy that has practical therapeutic value. PMID- 2230874 TI - Human tumor fluorouracil trapping: clinical correlations of in vivo 19F nuclear magnetic resonance spectroscopy pharmacokinetics. AB - We previously reported that fluorouracil (5FU) accumulation and metabolism in human livers and tumors can be studied by in vivo nuclear magnetic resonance spectroscopy (NMRS). We have extended these observations by evaluating the pharmacokinetics of 5FU in the tumors of 11 patients with carcinoma of the breast, colon, endometrium, cervix, and kidney, using 19F-NMRS in a 1.5 Magnetom (Siemens Medical Systems, Cerrito, CA) magnetic resonance imaging unit (MRI). These NMRS measurements detected a long-lived tumor pool of 5FU in six of 11 tumors in our patients including carcinomas in the pelvis, breast, lung, and liver. The half-life (T1/2) of this tumor pool of "trapped" 5FU was 0.33 to 1.3 hours (20 to 78 minutes), much longer than the T1/2 of 5FU in blood (5 to 15 minutes). Neither the anabolites of 5FU (fluorinated nucleosides, nucleotides, 5FU-RNA, or 5FU-thymidylate synthase) nor the catabolites (eg, fluorobetaalanine [FBAL]) were detectable by 19F NMRS. Patient response to chemotherapy appeared to correlate with the extent of trapping of free 5FU in the human tumors: in the seven patients receiving 5FU, or 5FU or FUdR plus leucovorin, four of four patients whose tumors trapped 5FU responded to fluorinated pyrimidine chemotherapy, whereas three patients in whom there was a failure to detect tumor trapping were resistant to 5FU. We conclude that NMRS is clinically feasible, and enables investigators to study 5FU pharmacokinetics and metabolism in tumors in vivo. 19F-NMRS of 5FU allows for in vivo evaluation of 5FU metabolic modulation and might be able to guide therapeutic decisions. PMID- 2230875 TI - Changes in the clearance of total and unbound etoposide in patients with liver dysfunction. AB - The disposition of total and non-protein-bound etoposide was investigated in 21 cancer patients receiving etoposide and cisplatin combination chemotherapy. Etoposide plasma concentrations were determined using a specific high-performance liquid chromatography (HPLC) method, and etoposide plasma protein binding was determined by equilibrium dialysis. The patients had a wide range of renal function (creatinine clearance, 32 to 159 mL/min/m2) and hepatic function (total bilirubin range, 0.3 to 21.5 mg/dL; aspartate aminotransferase [AST] range, 14 to 415 IU/L; serum albumin range, 2.7 to 4.1 g/dL). The mean etoposide total systemic clearance was not different in 15 patients with total bilirubin less than 1.0 mg/dL versus six patients with total bilirubin 1.1 to 21.5 mg/dL (18.7 +/- 5.9 mL/min/m2 v 26.4 +/- 10.7 mL/min/m2; t-test P = .06), with a trend toward higher total clearance in the patients with abnormal bilirubin values. However, the mean clearance of unbound etoposide was significantly lower in patients with increased total bilirubin (220 +/- 90 mL/min/m2 v 135 +/- 61 mL/min/m2; t-test P = .027). The fraction of etoposide unbound (fu) in plasma was significantly higher in patients with increased bilirubin (9% +/- 3% v 27% +/- 15%; t-test P = .002), explaining the trend toward higher total clearance in these patients. Etoposide clearance (total or unbound) in the 14 patients with measurable hepatic metastases was not different from the clearance in the seven patients without hepatic metastases. This study provides an explanation for why patients with increased bilirubin do not have lower total systemic clearance of etoposide, and indicates that such patients have a higher exposure to unbound etoposide. The results of ongoing pharmacodynamic studies of total and unbound etoposide in patients with increased bilirubin will determine the clinical relevance of altered etoposide protein binding. PMID- 2230876 TI - Clinical evaluation of a side entry access port: a novel dual-lumen venous access device. AB - The initial clinical experience with a low-profile side entry access (SEA) dual lumen implantable venous access port for cancer chemotherapy administration is summarized in this report. The catheter material is polyurethane. The overall experience in 35 patients in this study was a total of 6,224 patient days, with a mean of 178 days per patient. A variety of chemotherapeutic agents, biologic response modifiers, and antibiotics were administered. In 26% of the patients, the device chambers were in simultaneous use during the treatment period. A 6% incidence of clinical subclavian vein thrombosis was noted. There was no infectious complications. Inconsistencies in blood withdrawal and temporary catheter dysfunction were comparable to other access ports in clinical use. The novel design of this side entry port and the catheter material of low thrombogenicity make this device a good option in patients requiring a low profile system and dual access. Nursing staff should be made aware of the side entry design and that in-service training for accessing the septum is required in centers where such devices are not routinely used. PMID- 2230877 TI - Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33. AB - A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear. PMID- 2230878 TI - An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma. AB - An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross resistance to presently available antitumor drugs. PMID- 2230879 TI - The unique aspects of acute promyelocytic leukemia. AB - Acute promyelocytic leukemia (APL) accounts for approximately 10% of cases of acute myeloid leukemia (AML). Distinctive features of this disorder at the time of diagnosis include leukopenia coexisting with a marrow replaced with granulated dysplastic promyelocytes, disseminated intravascular coagulopathy, lack of Ia (HLA-DR) antigen expression, and translocation between the long arms of chromosomes 15 and 17 (t[15;17]). Heparin is widely but not universally used to interfere with the coagulopathy during the initial phases of treatment. Serial bone marrow examinations during the induction period demonstrate the achievement of remission despite the persistence of malignant-appearing promyelocytes. Patients with APL are generally younger than those with other subtypes of AML, have a 70% to 80% likelihood of entering remission, and are thought to have a more favorable prognosis than other individuals with AML. Remission may be achieved with a conventional anthracycline-cytarabine combination, anthracycline alone, or, apparently, all-trans retinoic acid. Genes potentially important in myeloid differentiation such as granulocyte colony-stimulating factor (G-CSF) and myeloperoxidase are located close to the breakpoint in the t(15;17) but have not been conclusively shown to be rearranged in the translocation. A better understanding of the unique aspects of APL may well shed light on the pathogenetic processes of AML. PMID- 2230880 TI - Chemohormonal therapy for older women with node-positive breast cancer. PMID- 2230881 TI - The reporting of trials of adjuvant therapy for breast cancer. PMID- 2230882 TI - What determines actual chemotherapy dose intensity? PMID- 2230883 TI - Dose intensity in the treatment of diffuse large-cell lymphoma. PMID- 2230884 TI - Concomitant chemoradiotherapy. PMID- 2230885 TI - The calculation of received dose intensity. PMID- 2230886 TI - Monoclonal antibodies and radioimmunoconjugates: keeping feasibility at center stage. PMID- 2230887 TI - Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer. AB - From March 1987 to March 1988, a phase I to II study was carried out in 25 patients with ovarian cancer. They received escalating doses of intraperitoneally (IP) administered yttrium-90 (Y-90)-labeled monoclonal antibody, HMFG1, against a tumor cell-surface antigen. Myelosuppression prevented an escalation of the administered Y-90 activity above 25 mCi. Y-90-labeled antibody was absorbed from the peritoneal cavity into the circulation. Maximum blood Y-90 activity was observed 40 hours after the IP injection with a mean of 21% of the injected activity (range, 14.2% to 26.4%) in the circulation. The radiation dose the bone marrow received from circulating Y-90-labeled antibody (the blood radiation dose) was calculated by applying the Medical Internal Radiation Dose (MIRD) formulation to the measured Y-90 activity in patients blood. Myelosuppression occurred following calculated blood radiation doses to bone marrow of only 10 to 30 cGy. The excessive myelosuppression following such modest radiation doses from circulating Y-90-labeled antibody could be explained by the uptake of Y-90 by bone. In an attempt to reduce bone absorption of Y-90, seven patients received an intravenous (IV) infusion of EDTA (Sinclair Pharmaceuticals Ltd, Godalming, United Kingdom). This increased the urinary excretion of Y-90 from a mean of 11.1% to 32.3% of the injected activity (P = .0001). Fourteen patients had assessable tumor at laparoscopy. Tumor regression was observed in one patient, and palliation of ascites in a further patient. PMID- 2230888 TI - Clinical correlates of distinct immunophenotypic and histologic subcategories of lymphocyte-predominance Hodgkin's disease. AB - Histologic and paraffin immunohistologic studies were carried out on 32 patients with lymphocyte-predominance Hodgkin's disease (LPHD) seen from 1970 through 1982. While nodular histology was accurately predictive of B-cell phenotype (Leu M1 -/L26+), diffuse histology corresponded to either B-cell or Hodgkin's (Leu M1 +/L26-) phenotype, not invariably predictable even when attention was paid to subtle paragranuloma cytology. Clinical characteristics were compared between histologic (diffuse v nodular) and immunophenotypic (Leu M1 +/L26-, Hodgkin's phenotype, v Leu M1 -/L26+, B-cell phenotype) subgroups. Ten patients have since died, and the median follow-up of the living patients was 14 years (range, 6 to 31). Of the several clinical parameters compared, only axillary nodal presentation was strongly associated with both B-cell phenotype and nodular histology, while male predominance related more to B-cell phenotype than nodular histology. No significant difference in overall survival or relapse rate was apparent among either the histologic or the immunophenotypic subgroups. However, very late but salvageable relapses were associated with nodular histology. The incidences of secondary malignancies and death from Hodgkin's disease (HD) were also comparable between the subgroups. Although difference in clinical presentation may exist, neither the histologic nor the immunophenotypic subcategories of LPHD could be demonstrated to correlate with differences in clinical outcome. PMID- 2230889 TI - Gallium-67 imaging: a predictor of residual tumor viability and clinical outcome in patients with diffuse large-cell lymphoma. AB - Durable complete remissions (CRs) can be achieved in patients with diffuse large cell lymphoma (DLCL) with multidrug chemotherapy. The length of time to reach CR may be predictive of treatment outcome. However, defining CR by chest radiograph or computed tomography (CT) is often difficult since residual abnormalities do not always indicate residual disease. We have prospectively evaluated the ability of gallium-67 citrate (Ga-67) imaging to define residual disease and predict outcome in 37 consecutive patients with DLCL. Patients received 296 to 370 megabecquerels (MBq) Ga-67 and were imaged prior to, following cycles 4 to 6, and at completion of intensive chemotherapy. Ga-67 scan results were correlated with radiographic studies. Seventeen of 37 patients (46%) showed persistent, abnormal Ga-67 uptake halfway through chemotherapy. Of these, four were in CR, 11 were in partial remission (PR), and two showed no change in tumor size. At follow-up, 10 (59%) have died (three who were scored as CR and seven who were in PR halfway through therapy), two are alive with active tumor, one relapsed and survives following bone marrow transplant, and four (three in PR and one in CR at the therapeutic halfway point) are without disease at a median of 28 months from presentation. Of the 20 patients who were Ga-67-negative halfway through therapy, 11 were in CR and nine were in PR. Five of 20 patients (25%) have died. Three, in radiographic CR died at 11, 26, and 28 months, and two in radiographic PR died at 15 and 17 months. One patient is alive with active tumor, and 14 patients (70%) are alive without disease at a median of 34 months from presentation. Ga-67 imaging proved to be an excellent indicator of residual viable tumor; a positive scan halfway through therapy predicted for a poor outcome and may well justify a change in treatment. PMID- 2230890 TI - Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. AB - Ninety-eight pediatric patients were treated with three separate protocols (Treatment and investigation of Osteosarcoma [TIOS] I, II, and III) and 47 developed recurrent disease (metastases and/or local recurrence). Actuarial overall disease-free survival (hereafter designated survival) was 43%. Over 90% of the patients were treated initially with preoperative intraarterial cisplatin (CDP). Postoperative chemotherapeutic regimens comprised high-dose methotrexate with leucovorin rescue (MTX-CF), Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH), and cyclophosphamide. Primary definitive treatment comprised amputation or limb salvage (TIOS I and TIOS III). Patients treated with preoperative CDP and surgery (TIOS I and III) had a 62% survival. Patients in TIOS II refused surgical extirpation; they were treated exclusively with chemotherapy and had a 23% survival. Survival in patients treated with amputation was 55% and limb salvage 58%. Prognostic factors considered significant in relation to development of pulmonary metastases comprised tumor burden (P = .04) and the percentage of tumor necrosis induced by preoperative chemotherapy (P = .01). Histopathologic subtype was marginally significant: chondroblastic was more favorable as opposed to osteoblastic (P = .05). These findings are compared with results and prognostic factors published in the literature. PMID- 2230891 TI - Early hospital discharge of children with cancer treated for fever and neutropenia: identification and management of the low-risk patient. AB - Children with leukemia and solid tumors are often hospitalized for empiric broad spectrum antibiotic therapy because of fever during periods of chemotherapy induced neutropenia. Conventional practice dictates that parenteral antibiotics be continued until the patient is afebrile and has recovered from neutropenia, ie, until the absolute neutrophil count (ANC) exceeds 500 cells per cubic millimeter. However, the practice in our center has been to discontinue parenteral antibiotic therapy and discharge many such patients before resolution of neutropenia. Since the feasibility and safety of this approach has not been studied, we reviewed the records of 114 consecutive hospitalizations for fever and neutropenia in 61 patients during a 13-month period. Seventy-seven children (68%) were discharged to their homes while still neutropenic after they had been afebrile for 1 to 2 days on parenteral antibiotics, had negative blood cultures, appeared well, and usually had some evidence of bone marrow recovery. Five patients (4.4%) developed recurrent fever and required rehospitalization within 7 days of discharge. Only three of the 77 patients (3.9%) who were sent home with neutropenia had recurrent fever. Each had a brief and uneventful second hospitalization. Two of the 37 children discharged with an ANC over 500 cells per cubic millimeter required rehospitalization. A declining ANC and advanced malignancy were risk factors in predicting recurrence of fever following discharge. A rising monocyte count was a predictor of imminent recovery from neutropenia. These results suggest that "early" discharge of an afebrile yet still neutropenic patient is safe when the patient is in remission, has no evidence of serious infection, appears clinically stable, and has indications of bone marrow recovery. The conventional approach of routinely continuing the hospitalization until resolution of neutropenia may be unnecessary in such low risk patients. PMID- 2230892 TI - Current urinary mass screening for catecholamine metabolites at 6 months of age may be detecting only a small portion of high-risk neuroblastomas: a chromosome and N-myc amplification study. AB - We studied 96 infants and children with untreated neuroblastomas. Chromosomes of tumor cells were analyzed in 68, and N-myc copy numbers were determined in 67 patients. Patients found by a mass screening program for 6-month-old infants (group A1, 39 patients) or those less than 12 months of age found clinically (group A2, 13 patients) were rarely in the disseminated stage (A1, three of 39; A2 one of 13); their tumors usually had near-triploid (3n) or hypertetraploid (greater than 4n) karyotypes (A1, 28 of 37; A2, nine of 11), and never had N-myc amplification (A1, zero of 34; A2, zero of 11). In contrast, children 12 months or over (group B, 27 patients) were usually in the disseminated stage (19 of 27) (P less than .0001); their tumors usually had near-diploid (2n) or near tetraploid (4n) karyotypes (16 of 20) (P = .0027), and often had N-myc amplification (nine of 22) (P less than .0001). Of the 40 clinically found patients (A2 and B), six had undergone the screening with a negative result at the age of 6 months. Two of the six patients had N-myc amplification in the tumors. Most tumors found by the screening showed known characteristics predicting a good prognosis, and the majority of tumors showing characteristics predicting a poor prognosis were found in patients aged between 12 and 36 months. Our chromosome and N-myc amplification studies suggest that a low-risk tumor does not usually evolve to a high-risk tumor. Thus, the current mass screening program may be detecting only a small portion of highly malignant neuroblastomas at the earliest stage. Infants should be screened twice, at 6 months as well as at 12 months of age, for the early detection of high-risk neuroblastomas. PMID- 2230893 TI - Mechlorethamine, vincristine, and procarbazine chemotherapy for recurrent high grade glioma in adults: a phase II study. AB - We undertook a phase II study of combination chemotherapy with mechlorethamine (nitrogen mustard) 6 mg/m2 intravenously day 1 and day 8, vincristine 2 mg intravenously day 1 and day 8, and procarbazine 100 mg/m2 orally days 1 through 14 (MOP) in adults with recurrent high-grade glioma. There were 31 patients entered and 27 patients assessable for response. The median age was 49 years old. All patients had prior maximal radiotherapy, and eight had previous chemotherapy. Responses were determined based on clinical and computed tomographic (CT) scan/magnetic resonance imaging (MRI) criteria. The response rate (partial response [PR] plus objective qualitative response [OQR] plus complete response [CR]) was 52% with one CR. The response rate was higher in patients with anaplastic astrocytoma as compared with glioblastoma multiforme (P less than .05). The median duration of response was 42 weeks. Median survival for all assessable patients was 30 weeks, and for responders, it was 60 weeks. Response was correlated with ability to decrease dexamethasone doses and improved performance status. Toxicity was mainly hematologic with leukopenia being common. There was one treatment-related death from listeria meningitis, and two patients developed Pneumocystis carinii pneumonia. There were three episodes of neutropenic fever. We conclude that MOP is active and merits further investigation in adult high-grade glioma. PMID- 2230894 TI - Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma. AB - We conducted a phase II clinical trial of fluorouracil (5FU) and recombinant interferon alfa-2a (rIFN alpha-2a) in 52 previously untreated patients with bidimensionally measurable metastatic colorectal cancer. During week 1, 5FU was administered as a continuous intravenous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting on day 12. rIFN alpha-2a (Roferon; Hoffman-LaRoche, Nutley, NJ), 9 x 10(6) U, was administered subcutaneously three times weekly during weeks 1 to 8. Patients were evaluated for response on week 9. Of 52 patients enrolled in the study, 51 were assessable for toxicity, and 45 were assessable for response. Fifteen patients experienced partial response, and one patient achieved a clinical complete response for an overall response rate of 35% (95% confidence interval [CI], 22%, 50%). Median duration of response is 7.5 months (range, 4 to 11 months). Seventy percent of patients entered on the study are alive with a median follow-up duration of 7 months. Twenty-five percent of patients developed grade 4 toxicity, and 82% developed grade 3 toxicity. One drug-related death in the presence of sepsis was reported, and two treatment-related seizures occurred. Our experience with this schedule produced a lower response rate with greater toxicity than previously reported. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid (leucovorin) or single-agent 5FU may determine its role in the treatment of advanced colorectal carcinomas. PMID- 2230895 TI - Adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with axillary node-positive breast cancer: an update of the Guy's/Manchester trial. AB - Between 1976 and 1985, 391 patients (202 premenopausal, 189 postmenopausal) with operable breast cancer and positive axillary lymph nodes were randomized after total mastectomy and axillary clearance to receive cyclophosphamide, methotrexate, and fluorouracil (CMF) (n = 193) or no adjuvant therapy (n = 198). After a median follow-up of 8 years, both relapse-free survival (RFS) and survival (S) were significantly prolonged in premenopausal patients receiving CMF (RFS, P less than .001; S, P = .003). Treatment with CMF resulted in a significant improvement in RFS in premenopausal patients both with steroid receptor-positive and steroid receptor-negative tumors and also in subgroups of premenopausal patients defined by the number of axillary nodes involved. Premenopausal patients who developed permanent amenorrhea following CMF had a significantly better RFS than those who continued to menstruate. Induction of amenorrhea following CMF was related to age, with almost all patients over 40 years becoming amenorrheic. For patients less than or equal to 40 years, development of amenorrhea following CMF did not influence outcome. No difference was detected between control and CMF groups (RFS, P = .9; S, P = .9) in postmenopausal patients nor in any subgroup of these patients. The results of this trial of the efficacy of CMF for improving RFS and S have strengthened with longer follow-up. PMID- 2230896 TI - Node-negative breast cancer: prognostic subgroups defined by tumor size and flow cytometry. AB - Adjuvant systemic therapy for women with node-negative breast cancer is most easily justified for those patients at highest risk of relapse. We have examined the impact of tumor size, histologic grade, estrogen receptor (ER) status, tumor ploidy, and S-phase fraction (SPF) on relapse-free survival (RFS) for 169 patients with node-negative breast cancer in order to identify groups of patients at high and low risk of relapse. Patients with small tumors (less than or equal to 1.0 cm) had a significantly better RFS than those with larger tumors (P = .005), with 96% remaining relapse-free at 5 years. Patients with tumors less than or equal to 1.0 cm were thus excluded from analysis when attempting to define a group with a poor prognosis. Within the group of patients with tumors greater than 1.0 cm, tumor ploidy (P = .63), ER status (P = .3), or progesterone receptor (PgR) status (P = .24) did not predict for RFS. Patients with grade 1 or 2 infiltrating ductal tumors had a significantly better prognosis than those with grade 3 tumors (P = .04). The prognostic factor that gave the widest separation between subgroups, however, was SPF. Patients whose tumors were greater than 1.0 cm with an SPF less than or equal to 10% had a 5-year RFS of 78% compared with a 5-year RFS of 52% for those with an SPF greater than 10% (P = .006). We have combined tumor size and SPF to identify three prognostic groups: (1) tumor less than or equal to 1.0 cm, 5-year RFS 96%; (2) tumor greater than 1.0 cm plus SPF less than or equal to 10%, 5-year RFS 78%; 3) tumor greater than 1.0 cm plus SPF greater than 10%, 5-year RFS 52%. These prognostic groupings may help identify patients most suitable for adjuvant therapy. PMID- 2230897 TI - Phase I clinical and pharmacologic study of intraperitoneal cisplatin and fluorouracil in patients with advanced intraabdominal cancer. AB - Fluorouracil (5-FU) and cisplatin display marked therapeutic synergy in preclinical models and are effective in the treatment of a number of solid tumors when combined and administered intravenously (IV). Each drug has also been administered intraperitoneally (IP) and displays a favorable pharmacologic profile and acceptable clinical toxicity. We therefore undertook a phase I study to determine the feasibility and toxicity of combination IP chemotherapy with these agents. Thirty-one patients with histologically documented malignancy confined to the peritoneal space were treated with cisplatin 90 mg/m2 mixed with 5-FU in 2 L of lactated Ringer's solution and given IP for 4 hours every 28 days. Cohorts of at least three patients received starting 5-FU concentrations ranging from 5 mmol/L (1,300 mg in 2 L) to 20 mmol/L. The dose-limiting toxicity was neutropenia with a median granulocyte nadir of 156 cells per microliter occurring at a 5-FU dose of 20 mmol/L. Intrapatient escalation of the 5-FU dose was permitted and 15 cycles of chemotherapy were delivered at 5-FU concentrations greater than 20 mmol/L, the highest concentration being 30.7 mmol/L (8 g of 5-FU in 2L). Other toxicities included mild to moderate nausea during all cycles of therapy, vomiting in 54% of cycles, and diarrhea in 15% of cycles. Abdominal pain, renal dysfunction, peripheral neuropathy, and oral mucositis occurred infrequently and were not related to the 5-FU dose. Peritoneal fluid and plasma 5 FU concentrations were measured by high-performance liquid chromatography (HPLC) in selected patients. Mean peak plasma 5-FU concentrations ranged from 6.19 mumol/L to greater than 60 mumol/L, and peritoneal fluid to plasma 5-FU area under the curve (AUC) ratios ranged from 85 to 1,150. Nine of 15 patients with nonbulky disease had resolution of malignant ascites or at least a 50% reduction of peritoneal studding by tumor at repeat laparotomy. We conclude that combination IP chemotherapy with cisplatin and 5-FU is technically feasible and has acceptable clinical toxicity and a favorable pharmacologic profile. The recommended starting 5-FU dose for phase II trials is 3,900 mg mixed with 90 mg/m2 of cisplatin in 2 L of isotonic fluid. PMID- 2230898 TI - Drug-induced DNA damage and tumor chemosensitivity. AB - Cytotoxic drugs act principally by damaging tumor-cell DNA. Quantitative analysis of this interaction provides a basis for understanding the biology of therapeutic cell kill as well as a rational strategy for optimizing and predicting tumor response. Recent advances have made it possible to correlate assayed DNA lesions with cytotoxicity in tumor cell lines, in animal models, and in patients with malignant disease. In addition, many of the complex interrelationships between DNA damage, DNA repair, and alterations of gene expression in response to DNA damage have been defined. Techniques for modulating DNA damage and cytotoxicity using schedule-specific cytotoxic combinations, DNA repair inhibitors, cell-cycle manipulations, and adjunctive noncytotoxic drug therapy are being developed, and critical therapeutic targets have been identified within tumor-cell subpopulations and genomic DNA alike. Most importantly, methods for predicting clinical response to cytotoxic therapy using both in vitro markers of tumor-cell sensitivity and in vivo measurements of drug-induced DNA damage are now becoming a reality. These advances can be expected to provide a strong foundation for the development of innovative cytotoxic drug strategies over the next decade. PMID- 2230899 TI - Further consideration of improved methodology for analyzing local and distant recurrence. PMID- 2230900 TI - Dose reduction of etoposide in jaundiced patients. PMID- 2230901 TI - Acute nonlymphocytic leukemia after radiation and MOPP chemotherapy for Hodgkin's disease. PMID- 2230902 TI - Oligodendroglioma: a new chemosensitive tumor. PMID- 2230903 TI - Potentiation of cisplatin ototoxicity by noise. PMID- 2230904 TI - Combination therapy in systemic mycosis. PMID- 2230905 TI - Impact of antimicrobial agents on human intestinal microflora. AB - The most common and significant cause of disturbances in the normal intestinal microflora is the administration of antimicrobial agents. The microflora can be influenced by antimicrobial agents because of incomplete absorption of any orally administered antimicrobial agent, secretion of an antimicrobial agent in the bile, or secretion from the intestinal mucosa. In most cases, the influence is not beneficial to the patient because suppression of the indigenous microorganisms often permits potential pathogens to overgrow and cause septic conditions, stomatitis, diarrhea, or colitis. Antimicrobial agents that influence the normal microflora also promote the emergence of antimicrobial-resistant strains. During the last fifteen years, the impact of different antimicrobial agents on the human microflora has been studied by several investigators. In this article published data on the impact of beta-lactam antibiotics, macrolides, tetracyclines, nitroimidazoles, clindamycin and quinolones on the human intestinal microflora are reviewed. PMID- 2230906 TI - Heavy metals, chlorine and antibiotic resistance in Escherichia coli isolates from ambulatory patients. AB - The susceptibility of Escherichia coli strains isolated from ambulatory patients to heavy metals, chlorine and antibiotics was evaluated. It seemed that heavy metal resistance was associated with antibiotic resistance. On the other hand, chlorine resistant strains seemed to be more sensitive to antibiotics. Clinical and ecological implications of these results are discussed. PMID- 2230907 TI - Resistance to apramycin in two enterobacterial clinical isolates: detection of a 3-N-acetyltransferase IV. AB - Considering the possible role of farm animals in the contamination of human consumers by plasmid-mediated apramycin-resistant enterobacteria strains, this type of resistance should be tested more systematically in human isolates. Very recently we isolated in Zaragoza one apramycin-resistant Escheria coli strain obtained from the blood of a hospitalized patient; this clinical isolate produced a plasmid-mediated 3-N-aminoglycoside acetyltransferase IV. We describe also the isolation in Madrid of one multiresistant Klebsiella pneumoniae clinical strain. This isolate harbored a single plasmid and carried determinants for apramycin, gentamicin, tobramycin, hygromycin B, streptomycin, and ampicillin, which could be transferred en bloc to E. coli K-12 J62. Extracts from donor and transconjugant strains carrying pUZ6776 plasmid produce acetyltransferase activity AAC(3)-IV and double phosphotransferase activity (HPH and APH(3'')). PMID- 2230908 TI - Acute prostatitis: which antibiotic to use first. AB - Six antimicrobial agents were administered to 48 patients (divided in 6 groups) who underwent prostatectomy. Half of the patients received the antibiotic in a single dose one hour before the operation and the rest in divided doses 24 hours before the operation. The concentration levels in serum and in prostatic tissue were measured for each of the antibiotics and for each mode of administration. The obtained ratios of prostatic tissue to serum concentrations and the relative antimicrobial activity to local pathogens of each agent indicate that the agent of choice for prostatic disease is netilmicin followed by aztreonam, cefuroxime and the ticarcillin-clavulanic acid combination. PMID- 2230909 TI - Imipenem/cilastatin treatment of acute infections in AIDS/ARC patients. AB - We studied the clinical efficacy and safety of imipenem, a broad spectrum beta lactam antibiotic, in acute bacterial infections in 21 patients with AIDS or AIDS related complex (ARC). Imipenem/cilastatin was administered as a 30-min intravenous infusion using a dose of 500 mg/8 h. Bacterial pathogens were isolated before treatment in 80% of cases; 87.5% of all strains were susceptible to imipenem in vitro. Treatment resulted in rapid control of the infections in 80% of patients. Clinical and laboratory adverse reactions probably related to imipenem treatment were noted in 8 patients. PMID- 2230910 TI - Prophylactic mezlocillin-netilmicin combination in permanent transvenous cardiac pacemaker implantation: a single-center, prospective, randomized study. AB - A prospective, randomized study was carried out in order to assess the efficacy and safety of the mezlocillin-netilmicin combination in the prophylaxis of first permanent transvenous cardiac pacemaker implantation. Five hundred and fifty-two consecutive patients were randomly administered either 2 g mezlocillin and 200 mg netilmicin both as an i.v. bolus before implantation or 2g mezlocillin before and then 6 and 12 hours after surgery and 200 mg netilmicin before and then 12 hours after implantation. No adverse events were seen. Neither pocket nor electrode infections were observed in the 457 subjects still alive (mean follow-up: 29.2 months) or in patients who died after 1 year of follow-up (mean follow-up: 20.1 months) or before this time (mean follow-up: 4.7 months). The serum and pocket concentrations of mezlocillin and netilmicin at the end of surgery were found to be adequate to cover microorganisms that most often cause infections, including methicillin-resistant staphylococci. PMID- 2230911 TI - Short-term antibiotic prophylaxis in open urologic surgery. AB - The aim of the present study was to compare the efficacy of a single dose of ceftriaxone with a triple dose of gentamicin as prophylactic agents in patients undergoing open urologic surgery. Fifty-two patients were allocated into two groups which were well matched with respect to sex, age and surgical procedure: - 24 were given single-dose ceftriaxone (2 g i.v.) at the time of anesthesia (ceftriaxone group); --28 received gentamicin (80 mg i.v.) at the time of anesthesia and two additional doses of the same antibiotic were subsequently administrated every 8 hours (gentamicin group). The incidence of urinary tract infection (UTI) was 3.5% in the gentamicin group and 0% in the ceftriaxone group (p = n.s.); postoperative fever (greater than 38 degrees C) occurred in 28.3% and 8.3% in the gentamicin and ceftriaxone groups respectively (p = n.s.). There was no clinical or hematological evidence of drug side effects in any patient. Results of the study show that short-term antibiotic regimens can improve UTI rates after open urologic surgery; moreover a single preoperative dose of ceftriaxone resulted to be as effective as three doses of gentamicin. PMID- 2230912 TI - Advanced epithelial ovarian cancer: no difference in survival rate between exploratory laparotomy and inadequate debulking surgery as treatment approach before chemotherapy. AB - In this study we have retrospectively evaluated 40 untreated patients with stage III-IV (FIGO) epithelial ovarian cancer. Sixteen patients had received, as initial treatment, inadequate surgical removal of the tumor with bulky residue (BR) of disease and 24 had had an exploratory laparotomy (EL) only. Subsequently, both groups received equivalent chemotherapy consisting of AC combination (adriamycin, cyclophosphamide) in 25 patients. Following surgery plus chemotherapy the two groups achieved a similar high remission rate (BR patients: 73% with AC scheme and 80% with PEC scheme; EL patients: 57% with AC and 100% with PEC). Furthermore, when all responsive patients were surgically re-explored, there was a pathologically complete remission in 5/12 BR patients and in 4/10 EL patients. Median survival was 20 months (range 3-50) in BR patients and 16 months (range 3-31) in EL patients. The statistical comparison between the two groups showed no significance; similarly, there was no significant difference in comparing AC-treated with PEC-treated patients. These data show that in poor risk patients with advanced ovarian carcinoma, inadequate surgery with BR is not prognostically superior to EL alone; therefore, chemotherapy as first treatment approach could be a valid alternative to surgery in such cases. PMID- 2230913 TI - Cardiotoxicity during chemotherapy treatment with 5-fluorouracil and cisplatin. AB - Cardiotoxicity of 5-fluorouracil and cisplatin chemotherapy for esophageal, head and neck and gastric carcinoma was studied. Before treatment all patients had a cardiac evaluation and during treatment serial electrocardiographic (ECG) recordings were performed. In the pre-treatment evaluation signs of cardiovascular disease were found in 31(38.75%) patients. During treatment cardiotoxicity was observed in 12(15%) patients. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and arrhythmia. This study suggests that patients on 5-fluorouracil and cisplatin treatment should be under close supervision and that the treatment should be discontinued if chest pain and/or arrhythmias are observed. PMID- 2230915 TI - Organizing principles for single-joint movements. IV. Implications for isometric contractions. AB - 1. Normal human subjects made isometric pulse and step contractions about the elbow to visually defined target torques of different amplitudes and at different rates. We measured joint torque and electromyograms (EMG) from two agonist and two antagonist muscles. 2. When the task specification requires that the subject explicitly alter the rate at which torque is increased, the rates of rise of the agonist and antagonist EMG bursts covary with the rate of rise of the torque. For pulses of torque the duration of motoneuron excitation varies with the duration of the task-defined contractile event. 3. When a subject is asked to generate torques of different amplitudes without specifying a time interval, torque amplitude is positively correlated with how long, and therefore how high, the EMG rose. Subjects usually proportionately covary the strength of the agonist and antagonist contractions but are not constrained to do so. Some subjects use a strategy of varying the antagonist inversely with the agonist contraction. 4. We extend the organizing principles for the control of movement about a single joint to the control of isometric torque. These rules state that control of torque about a single joint is exercised by one of two strategies: the speed-sensitive strategy modulates the rate at which contraction rises by varying the intensity of motoneuron-pool excitation. The speed-insensitive strategy varies the duration over which contraction rises but does not change the rate. These two respective patterns of torque emerge from pulse-height and pulse-width modulation of motoneuron-pool excitation. 5. The rules defining speed-sensitive and speed insensitive strategies for movements are broadened for isometric contractions because of the wider range of torque patterns that we observe under these conditions. We propose a step-excitation component for prolonged isometric step contractions and slowly rising ramp patterns of excitation for contractions that develop over several hundreds of milliseconds. 6. The choice of strategies is based on task-specific torque requirements. The same two strategies that control torque to produce movement apply to the control of isometric torque. Unlike movements, however, isometric tasks are more often controlled by a blending of the two patterns. Possible reasons for this are discussed. PMID- 2230914 TI - Model of synchronized epileptiform bursts induced by high potassium in CA3 region of rat hippocampal slice. Role of spontaneous EPSPs in initiation. AB - 1. We constructed a computer model of the in vitro CA3 region of the rat hippocampal slice bathed in a high-potassium medium. Our aim was to understand better the mechanisms of initiation of synchronized bursts and the processes that regulate the interburst interval in the experimental system. 2. Our model began with a previously published model of the longitudinal CA3 hippocampal slice. The model contains three interconnected cell populations: 9,000 (excitatory) pyramidal cells; 450 inhibitory cells whose postsynaptic action is somatic and decays quickly, corresponding to chloride-dependent inhibition mediated by gamma aminobutyric acid (GABA)A channels, and 450 inhibitory cells whose postsynaptic action is dendritic, of delayed onset and long lasting, that corresponds to K dependent inhibition mediated by GABAB channels. 3. The model was then modified to account for specific features of the high-K experimental system: 1) the pyramidal cells do not generate intrinsic bursts; 2) EIPSP(CI) and EK are both shifted in a depolarizing direction; 3) spontaneous (i.e., not caused by presynaptic firing) excitatory postsynaptic potentials (EPSP)s were included; and 4) a steady current was injected into the pyramidal cells to depolarize them. 4. This model generates synchronized population bursts with interburst intervals of approximately 1.0-1.5 s. Bursts in individual pyramidal cells are preceded by barrages of EPSPs. These results agree with experiment. 5. Our model agrees with the following additional experiments: 1) synchronized bursts are abolished by partial blockade of excitatory synapses; 2) burst frequency is increased by partial blockade of a slow-intrinsic-K conductance; and 3) blockade of chloride dependent inhibition leads to bursts of longer duration with longer interburst intervals. 6. The basic structural features of this model are similar to, but not identical to, the model of the disinhibited hippocampal slice. Spontaneous EPSPs appear to be critical in the high-K system for initiating, but not for synchronizing, population bursts. The experimental data and simulation results raise interesting questions about the role of spontaneous EPSPs in initiating synchronized discharges in other epileptic systems and on the possible role of spontaneous EPSPs in the normal brain. PMID- 2230916 TI - Independent influences of rod adaptation on cone-mediated responses to light onset and offset in distal retinal neurons. AB - 1. The influence of rod adaptation on cone-mediated intracellular responses of distal retinal neurons was examined in the larval tiger salamander. Rods were selectively stimulated by the use of 450-520 nm adapting stimuli too dim to appreciably influence cones. Cones were primarily stimulated with the use of deep red stimuli (maximally sensitive to wavelengths greater than 650 nm). The qualitative properties of rod-cone interaction were assessed with the use of several different photic-stimulus paradigms. 2. Confirming results of prior studies, we showed that rod adaptation changed the time course of cone-mediated responses to the onset of square-wave light flashes in horizontal cells (HCs); rod adaptation had no similar influence in other distal retinal neurons. Rod adaptation also enhanced cone-mediated responses to rapid flicker in cones, hyperpolarizing (HPBCs) and depolarizing (DPBCs) bipolar cells, as well as HCs. 3. We also examined the influence of rod-stimulating background fields on cone mediated responses to slow (approximately 1-Hz) flicker composed of sawteeth with a rapid onset (ramp offset) or with a rapid offset (ramp onset). Such stimulation maintained a constant state of long-term adaptation while providing cones with transient-ON or transient-OFF stimulation. 4. Rod adaptation speeds up the response of HCs to rapid onset and increases response amplitude. Rod adaptation had no reliable influence on response to rapid onset in cones or bipolar cells. 5. Rod adaptation enhanced the amplitude of responses of HCs to rapid offset without altering response time course. 6. Rod adaptation greatly enhanced the amplitude of DPBC responses to rapid offset having no reliable influence on the time course of the response. 7. Rod adaptation caused responses of HPBCs to rapid offset to become much more transient. Rod backgrounds had a similar but smaller and less reliable influence on the response of cones to rapid offset. 8. The foregoing results indicate that rod adaptation exerts a minimum of two separate influences on cone-mediated responses in distal amphibian retina. Changes at light onset must reflect the operation of a mechanism that alters response kinetics of the HC membrane. Changes at light offset reflect the operation of a separate mechanism or set of mechanisms that must act in part presynaptically to the HCs. PMID- 2230918 TI - Purkinje cell simple spike activity during grasping and lifting objects of different textures and weights. AB - 1. Three monkeys (2.5-3.5 kg) were trained to pinch an object between the thumb and forefinger and to lift it a vertical distance of 1.0-2.0 cm. Either the object weight (15, 65, or 115 g) or the surface texture (sand paper or polished metal) contacting the fingers could be varied. The object was equipped with a vertical position transducer, an accelerometer, and strain gauges that measured the grip force and the vertical load force. 2. In accordance with similar previously published studies on human subjects, it was found that monkeys appropriately scaled the grip forces according to the weight and coefficient of friction of the object. The grip force preceded the load force by 25 ms, and they both covaried with the changes in surface friction. 3. An analysis of electromyograms (EMGs) recorded intramuscularly from the muscles of the wrist and fingers including both flexors and extensors indicated that 26 muscles were active during pinching and lifting. Of these, 17 produced the maximum activity for the slippery surface and the greatest weight and the least activity with the roughest surface and lightest weight. 4. A total of 59 Purkinje cells and 123 unidentified units recorded from the paravermal and lateral cerebellar cortex were found to change their firing frequency during lifting the experimental object. 5. Increased discharge during the grasping and lifting was found for 56% (33/59) of the Purkinje cells and 80% (98/123) of the unidentified neurons, whereas 44% (26/59) of the Purkinje cells and 20% of the unidentified neurons decreased activity during the same period. 6. Significant modulations of the firing frequency with surface texture or object weight occurred for 59% (35/59) of the Purkinje cells and 67% (82/123) of the unidentified neurons. 7. One hundred and three Purkinje and unidentified neurons recorded in the paravermal and lateral region of the cerebellar cortex were examined for peripheral receptive fields, and of these, 43/103 (42%) responded exclusively to imposed displacements and tapping of muscles suggesting afferents originating from proprioceptors. A further 28/103 (27%) had exclusively cutaneous receptive fields on the hand that could be stimulated by brushing the skin lightly with a sable hair brush. Only six neurons demonstrated convergent cutaneous and proprioceptive receptive fields and no response to peripheral stimulation could be found for 26 neurons. No difference was found between the receptive fields of Purkinje cells and those of the unidentified neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230917 TI - Inferotemporal units in selective visual attention and short-term memory. AB - 1. This research was designed to further clarify how, in the primate, the neurons of the inferotemporal (IT) cortex support the cognitive functions of visually guided behavior. Specifically, the aim was to determine the role of those neurons in 1) selective attention to behaviorally relevant features of the visual environment and 2) retention of those features in temporary memory. Monkeys were trained in a memory task in which they had to discriminate and retain individual features of compound stimuli, each stimulus consisting of a colored disk with a gray symbol in the middle. A trial began with brief presentation of one such stimulus, the sample for the trial. Depending on the symbol in it, the monkey had to memorize the symbol itself or the background color; after 10-20 s of delay (retention period), two compound stimuli appeared, and the animal had to choose the one with the symbol or with the color of the sample. Thus the test required attention to the symbol, in some trials also to the color, and short-term retention of the distinctive feature for each trial, either a symbol or a color. Single-unit activity was recorded from cortex of the IT convexity, lower and upper banks of the superior temporal sulcus (STS), and from striate cortex (V1). Firing frequency was analyzed during intertrial periods and during the entirety of every trial, except for the (match) choice period. 2. In IT cortex, as in V1, many units responded to the sample stimulus. Some responded indiscriminately to all samples, whereas others responded selectively to one of their features, i.e., to one symbol or to one color. Fifteen percent of the IT units were symbol selective and 21% color selective. These neurons appeared capable of extracting individual features from complex stimuli. Some color cells (color-attentive units) responded significantly more to their preferred color when it was relevant (i.e., had to be retained) than when it was not. 3. The latency of IT-unit response to the sample stimulus was, on the average, relatively short in unselective units (mean 159 ms), longer in symbol units (mean 203 ms), and longest in color-attentive units (mean 270 ms). This order of latencies corresponds to the presumed order of participation of those three types of units in the selective attention to the component features of the sample as required by the task. It suggests intervening steps of serial processing before color information reached color-attentive cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230919 TI - Characteristics of electrically induced locomotion in rat in vitro brain stem spinal cord preparation. AB - 1. Electrical stimulation of two brain stem regions in the decerebrate neonatal rat brain--the mesencephalic locomotor region (MLR) and the medioventral medulla (MED)--were found to elicit rhythmic limb movements in the hind-limb-attached, in vitro, brain stem-spinal cord preparation. 2. Electromyographic (EMG) analysis revealed locomotion similar to that observed during stepping in the adult rat. The step-cycle frequency could be increased by application of higher-amplitude currents; but, unlike the adult, alternation could not be driven to a gallop. 3. Threshold currents for inducing locomotion were significantly lower for stimulation of the MED compared with the MLR. Brain stem transections carried out at midpontine levels demonstrated that the presence of the MLR was not required for the expression of MED-stimulation-induced effects. 4. Substitution of the standard artificial cerebrospinal fluid (aCSF) by magnesium-free aCSF did not affect interlimb relationships and resulted in a significant decrease of the threshold currents for inducing locomotion. 5. Fixation of the limbs during electrical stimulation of brain stem sites altered the amplitude and duration of the EMG patterns, but the basic rhythm and timing of each muscle contraction during the step cycle was not affected. 6. These studies suggest that, although peripheral afferent modulation is evident in the neonatal locomotor control system, descending projections from brain stem-locomotor regions appear capable of modulating the activity of spinal pattern generators as early as the day of birth. However, there may be ceiling to the maximal frequency of stepping possible at this early age, perhaps suggesting a later-developing mechanism for galloping. PMID- 2230920 TI - Identification of histaminergic neurons in Aplysia. AB - 1. We have identified putative histaminergic neurons in the central nervous system of Aplysia californica by light-microscopic autoradiography after uptake of [3H]histamine and by immunohistochemistry with the use of an antibody specific for histamine. 2. In the cerebral ganglion cells previously shown to contain histamine (C2 and 2 large neighboring cells in the E cluster and a group of smaller cells in the L cluster) were identified both by uptake of [3H]histamine and by histamine immunoreactivity. The identification of C2 was confirmed by experiments in which individual C2s were characterized electrophysiologically and injected with Lucifer yellow before processing for immunohistochemistry. The giant serotonergic neuron did not take up [3H]histamine and was not immunoreactive. 3. In the abdominal ganglion two clusters of cells--one in the left hemiganglion and the other in the right--took up [3H]histamine and were histamine immunoreactive. These clusters are located in the regions occupied by the 30 identified respiratory interneurons, R25 and L25. Individual cells in the R25 and L25 clusters were identified electrophysiologically, marked by injection of Lucifer yellow, and processed for immunocytochemistry. Eleven of the 30 L25 cells examined (from 7 ganglia) and 2 of the 25 R25 cells (from 6 ganglia) that had been marked with Lucifer yellow were also histamine immunoreactive. 4. Also in the abdominal ganglion, identified cells in the L32 cluster were not histamine immunoreactive and did not take up [3H]histamine. These interneurons, which mediate presynaptic inhibition, had previously been considered histaminergic. Neurons in the ganglion known to use transmitters other than histamine (L10, R2, RB cells, and bag cells) were not histamine immunoreactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230921 TI - Adaptive control for backward quadrupedal walking. I. Posture and hindlimb kinematics. AB - 1. To gain new perspectives on the neural control of different forms of quadruped locomotion, we studied adaptations in posture and hindlimb kinematics for backward (BWD) walking in normal cats. Data from four animals were obtained from high-speed (100 fr/s) cine film of BWD treadmill walking over a range of slow walking speeds (0.3-0.6 m/s) and forward (FWD) treadmill walking at 0.6 m/s. 2. Postural adaptations during BWD walking included flexion of the lumbar spine, compared to a relatively straight spine during FWD walking. The usual paw-contact sequence for FWD walking [right hindlimb (RH), right forelimb (RF), left hindlimb (LH), left forelimb (LF)] was typically reversed for BWD walking (RH, LF, LH, RF). The hindlimbs alternated consistently with a phase difference averaging 0.5 for both forms of walking, but the phasing of the forelimbs was variable during BWD walking. 3. As BWD walking speed increased from 0.3 to 0.6 m/s, average hindlimb cycle period decreased 21%, stance-phase duration decreased 29%, and stride length increased 38%. Compared to FWD walking at 0.6 m/s, stride length was 30% shorter, whereas cycle period and stance-phase duration were 17% shorter for BWD walking. For both directions, stance occupied 64 +/- 4% (mean +/- SD) of the step cycle. 4. During swing for both forms of walking, the hip, knee, and ankle joints had flexion (F) and extension (E1) phases; however, the F-E1 reversals occurred earlier at the hip and later at the knee for BWD than for FWD walking. At the ankle joint, the ranges of motion during the F and E1 phases were similar for both directions. During BWD walking, however, the knee flexed more and extended less, whereas the hip flexed less and extended more. Thus horizontal displacement of the limb resulted primarily from hip extension and knee flexion during BWD swing, but hip flexion and knee extension during FWD swing. 5. At the knee and ankle joints, there were yield (E2) and extension (E3) phases during stance for both forms of walking; however, yields at the knee and ankle joints were reduced during BWD walking. At the hip, angular motion was unidirectional, as the hip flexed during BWD stance but extended during FWD stance. Knee extension was the prime contributor to horizontal displacement of the body during BWD stance, but hip extension was the prime contributor to horizontal displacement during FWD stance. 6. Our kinematic data revealed two discriminators between BWD and FWD walking.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230922 TI - Adaptive control for backward quadrupedal walking. II. Hindlimb muscle synergies. AB - 1. To compare the basic hindlimb synergies for backward (BWD) and forward (FWD) walking, electromyograms (EMG) were recorded from selected flexor and extensor muscles of the hip, knee, and ankle joints from four cats trained to perform both forms of walking at a moderate walking speed (0.6 m/s). For each muscle, EMG measurements included burst duration, burst latencies referenced to the time of paw contact or paw off, and integrated burst amplitudes. To relate patterns of muscle activity to various phases of the step cycle, EMG records were synchronized with kinematic data obtained by digitizing high-speed cine film. 2. Hindlimb EMG data indicate that BWD walking in the cat was characterized by reciprocal flexor and extensor synergies similar to those for FWD walking, with flexors active during swing and extensors active during stance. Although the underlying synergies were similar, temporal parameters (burst latencies and durations) and amplitude levels for specific muscles were different for BWD and FWD walking. 3. For both directions, iliopsoas (IP) and semitendinosus (ST) were active as the hip and knee joints flexed at the onset of swing. For BWD walking, IP activity decreased early, and ST activity continued as the hip extended and the knee flexed. For FWD walking, in contrast, ST activity ceased early, and IP activity continued as the hip flexed and the knee extended. For both directions, tibialis anterior (TA) was active throughout swing as the ankle flexed and then extended. A second ST burst occurred at the end of swing for FWD walking as hip flexion and knee extension slowed for paw contact. 4. For both directions, knee extensor (vastus lateralis, VL) activity began at paw contact. Ankle extensor (lateral gastrocnemius, LG) activity began during midswing for BWD walking but just before paw contact for FWD walking. At the ankle joint, flexion during the E2 phase (yield) of stance was minimal or absent for BWD walking, and ankle extension during BWD stance was accompanied by a ramp increase in LG-EMG activity. At the knee joint, the yield was also small (or absent) for BWD walking, and increased VL-EMG amplitudes were associated with the increased range of knee extension for BWD stance. 5. Although the uniarticular hip extensor (anterior biceps femoris, ABF) was active during stance for both directions, the hip flexed during BWD stance and extended during FWD stance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230923 TI - Functional organization within the medullary reticular formation of intact unanesthetized cat. I. Movements evoked by microstimulation. AB - 1. The present article described the various patterns of movement evoked in the limbs and neck by microstimulation (33-ms trains, 330 Hz, 0.2-ms pulses at less than or equal to 35 microA) of the medullary reticular formation (MRF) of seven chronically implanted, unanesthetized, intact cats. Altogether 878 loci were stimulated in 83 penetrations. However, as stimulation in the more lateral regions of the MRF was less effective, the results are based on stimulation in 592 loci made in 56 penetrations at distances of between 0.5 and 2.5 mm lateral to the midline. 2. Of these 592 loci, movement of one or more parts of the body was evoked from a total of 539 (91%) sites. Most of these movements were compound in nature, involving movement of one or more limbs as well as the head. Discrete movements were observed only with respect to the head; limb movements were always accompanied by head movement. In addition, hindlimb movements were always accompanied by forelimb movements, although the inverse was generally not true. 3. The most common effects of the stimulation were as follows: a turning of the head to the ipsilateral side (79% of stimulated sites); flexion of the ipsilateral elbow (41%); and extension of the contralateral elbow (45%). Effects in the hindlimbs were more variable and less frequent, with the majority of the effective loci causing flexion of the ipsilateral knee (9%) together with extension of the contralateral knee (8%). In total, including both flexion and extension, 18% of the stimulated sites caused movement of the ipsilateral hindlimb and 11% of the contralateral hindlimb. 4. Although movements of the head were obtained from the whole extent of the brain stem, movements of the forelimbs showed a dorsoventral organization with flexion of the ipsilateral elbow being evoked from the more dorsal regions of the brain stem, whereas contralateral elbow extension was evoked more frequently from the ventral regions. There was a large area of overlap from which movements of both limbs could be obtained simultaneously. Movements of the hindlimbs were more frequently evoked from central and ventral areas of the brain stem and from the most rostral aspect of the explored region. 5. In examining the combinations of movements evoked by the MRF stimulation, it was found that the most commonly evoked pattern was movement of the head to the stimulated side together with flexion of the ipsilateral forelimb and extension of the contralateral forelimb (26.5% of sites).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230924 TI - Functional organization within the medullary reticular formation of intact unanesthetized cat. II. Electromyographic activity evoked by microstimulation. AB - 1. The present study has examined the detailed organization of the medullary reticular formation (MRF) as revealed by microstimulation (33-ms trains of 0.2-ms duration pulses at 330 Hz and 35 microA or less) in the intact, chronically implanted, unanesthetized cat. Stimulus-locked electromyographic (EMG) responses were recorded from flexors and extensors of each of the four limbs, as well as bilaterally from muscles of the neck and back, during stimulation of the same 592 loci that formed the basis of the preceding article. 2. The thresholds of the responses were different for each group of muscles, with, on the average, the neck muscles being activated at the lowest range of currents, 13.8-16.5 microA; forelimb muscles at 16.9-17.9 microA; back muscles at 25.4-25.7 microA; and hindlimb muscles at 21.1-25.7 microA. 3. Whereas stimulation within the MRF evoked movement of the head only to the stimulated side (preceding article), analysis of the EMG responses showed there was frequently bilateral activation of the neck muscles. Similarly, even though stimulation produced predominantly ipsilateral elbow flexion and contralateral elbow extension, most loci caused cocontraction of antagonistic muscles at these joints. Cocontraction was also frequently observed for the hindlimbs. Reciprocal activation of antagonistic muscles was less frequent but was observed in the ipsilateral forelimb as well as in both hindlimbs; it was never observed in the contralateral forelimb. 4. Although excitatory responses were observed from widespread regions for all of the muscles under study, those regions of the MRF that evoked the strongest responses in each muscle showed a large degree of segregation. Muscles of the ipsilateral forelimb were most strongly activated from the rostrodorsal MRF, whereas muscles of the contralateral forelimb were most strongly effected by stimulation caudoventrally. Muscles of the hindlimbs were more strongly activated from the rostral brain stem, although with some exceptions. Responses in axial muscles were evoked from widespread regions of the brain stem but were concentrated further caudally than were the limb muscles. 5. Excitatory responses were much more prevalent than inhibitory responses and were evoked from all regions of the MRF, including the most caudal and ventral areas. The shortest latency responses in each track were, on the average, as follows: 6.6-8.8 ms for the neck; 11.2-13.4 ms for the forelimbs; 13.8-14.2 ms for the back; and 15.9 17.2 ms for the hindlimbs. Inhibitory responses were also evoked from widely distributed regions, which were intermingled with those loci evoking excitatory responses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230925 TI - Stimulus-response function studies of esophageal mechanosensitive nociceptors in sympathetic afferents of opossum. AB - 1. Single-unit activity was recorded from afferent fibers in either the paravertebral sympathetic chain or the splanchnic nerves. Forty-three fibers that responded to distension of the smooth-muscle portion of esophagus were selected for further study. 2. Out of the 43 fibers, 27 (62%) had ongoing resting activity, and 16 (38%) were silent. The mean resting activity of these fibers was 0.28 +/- 0.06 imp/s (range, 0-2.6 imp/s). 3. Repeated distensions of the esophagus to a fixed pressure (80 mmHg) evoked spike discharge at a reproducible rate. There was no evidence of facilitation or inhibition of subsequent responses. The mean coefficient of variation (CV) was 0.17 +/- 0.05 imp/s (n = 5). 4. The stimulus-response function (SRF) to intraluminal graded distension was studied in 35 fibers. Thirty-three fibers showed linear increase in firing that did not saturate up to 120 mmHg. Two fibers reached maximal discharge rate at 60 mmHg. The mean discharge rate at 120 mmHg pressure was 14.87 +/- 1.52 imp/s. 5. Threshold pressure for activation of each fiber was calculated by a least-squares linear-regression plot of the SRF. The threshold pressure varied from 0 to 50 mmHg (mean, 16.21 +/- 2.86 mmHg). The distribution profile of the threshold values showed that there were two separate populations of mechanosensitive receptors: 1) wide-dynamic-range mechanonociceptors (WDR-MN) with mean threshold pressure of 2.89 +/- 0.75 mmHg (range, 0-7 mmHg; n = 22); and 2) high-threshold mechanonociceptors (HT-MN) with mean threshold of 33.26 +/- 2.52 mmHg (range, 19 50 mmHg; n = 13). 6. Discharge evoked by esophageal peristalsis was studied in five WDR-MN and five HT-MN units. Whereas all five WDR-MN units (threshold value, 2.6 +/- 0.96 mmHg) responded to peristalsis, none of the HT-MN units (threshold value, 31.2 +/- 4.01 mmHg) did so. The mean response to peristaltic contraction in WDR-MN units was 5.32 +/- 1.36 imp/s, which was 24.7% of the maximal response (21.53 +/- 1.92 imp/s; n = 5) at 120 mmHg. The duration of evoked response to peristaltic contraction was 10-12 s. 7. The activity profile of the units to 60-s balloon distension at near threshold and higher pressures showed three patterns: 1) rapid adaptation, 2) slow adaptation, and 3) slow adaptation with after discharge. The rapidly adapting fibers became slowly adapting with greater degrees of esophageal distension. The units that showed rapid or slow adaptation at low-distension pressure became indistinguishable from one another at high distension pressure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230926 TI - Ensemble discharge from Golgi tendon organs of cat peroneus tertius muscle. AB - 1. The responses of individual tendon organs of the cat peroneus tertius muscle to motor-unit contractions were recorded in anesthetized cats during experiments in which all the Ib-afferent fibers from the muscle had been prepared for recording in dorsal root filaments. This was possible because the cat peroneus tertius only contains a relatively small complement of approximately 10 tendon organs. 2. Motor units of different physiological types were tested for their effects on the whole population of tendon organs in the muscle. Effects of unfused tetanic contractions were tested under both isometric and anisometric conditions. Each motor unit activated at least one tendon organ, and each tendon organ was activated by at least one motor unit. Individual slow-type units were found to act on a single or two receptors, whereas a fast-type unit could activate up to six tendon organs. 3. In one experiment, the effects of 8 motor units on 10 tendon organs were examined. One fast-twitch, fatigue resistant (FR) type unit acted on six tendon organs, of which four were also activated by another FR unit. The contraction of each unit, on its own, elicited a range of individual responses, from weak to strong. The discharge frequencies of individual responses displayed no clear relation with the strength of contraction, nor did they accurately represent the shape of force profiles. But when all the discharges were pooled, a fairly good correspondence appeared between variations of contractile force and variations of averaged discharge frequencies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230927 TI - Distribution and response properties of cat SI neurons responsive to changes in tooth temperature. AB - 1. The activity of 214 tooth pulp-driven neurons (TPNs) in the primary somatosensory cortex (SI) activated by electrical stimulation of the canine tooth pulp was studied in anesthetized cats. These neurons were tested for their responses to thermal stimulation of the tooth pulp. 2. One hundred fifty-five TPNs were not responsive to changes in tooth temperature (thermally insensitive, TINS-TPNs) and 59 TPNs were responsive (thermally sensitive, TS-TPNs: 38 TS-TPNs were heat sensitive and 21 were cold sensitive). TS-TPNs were also tested for responsiveness to mechanical and thermal stimulation of the skin, mucosa, or periodontal membrane. Each TS-TPN was classified on the basis of cutaneous, mucosal, or periodontal mechanical receptive-field properties as either low threshold mechanoreceptive (LTM: 57%), wide dynamic range (WDR: 25%), nociceptive specific (NS: 10%) or pulp specific (PS: 8%). 3. TS-TPNs were distributed in an upper bank of the orbital sulcus of SI. The majority were located in laminae III (32%) and IV (60%) of area 3b. 4. Heat-sensitive LTM, WDR, PS TS-TPNs, and cold sensitive LTM TS-TPNs were characterized by a rapid rise in firing rate during thermal stimulation of the tooth pulp. In contrast, heat-sensitive NS and cold sensitive NS and PS TS-TPNs responded with a slow rise in firing frequency during thermal stimuli delivered to the tooth pulp. 5. A linear regression analysis was applied to the stimulus-response functions of neuronal discharges of TS-TPNs. Fifty-six percent of heat-sensitive LTM, WDR, and cold-sensitive LTM TS-TPNs showed statistically significant relation (P less than 0.5) between peak firing frequency and stimulus temperature and increasing firing frequency after increases in stimulus temperature, whereas heat-sensitive and cold-sensitive NS and PS TS-TPNs did not show a clear increase in firing frequency during the thermal stimulus. 6. These findings suggest that heat-sensitive LTM and WDR TS TPNs and cold-sensitive LTM TS-TPNs that showed high regression coefficients in stimulus-response function may be involved in encoding the intensity of noxious thermal stimulation of the tooth pulp. PMID- 2230928 TI - Ipsilateral and contralateral effects on cutaneous reflexes in a back muscle of the female rat: modulation by steroids relevant for reproductive behavior. AB - 1. Multiunit EMG recordings of cutaneous reflexes--evoked in the back extensor, lateral longissimus (LL), by bilateral stimulation of nerves to dorsal flank skin -were studied in ovariectomized female rats with and without estrogen pretreatment. 2. Poststimulus time (PST) histograms of data from rats with and without estrogen pretreatment show that the axial EMG response (10-30 ms) to ipsilateral (ipsi) flank skin nerve stimulation is significantly shorter in latency (1.4 ms) and 67% larger than the response to contralateral (contra) flank skin nerve stimulation recorded at the same site (n = 29 pairs). 3. When late EMG responses were also evoked at 50-120 ms in 37% of ipsi and 29% of contra cutaneous reflexes, the incidence of multiunit activity in the late peak was significantly greater in rats pretreated with silastics containing 100% estradiol (E) compared with 10% E or cholesterol controls. 4. When an ipsi cutaneous reflex in LL was conditioned by a stimulus to the contra flank skin nerve at a condition test interval of 30 ms (C-T 30 ms), the average number of discharges in the early peak of the histogram was double that in the histogram obtained from the unconditioned ipsi reflex, independent of estrogen pretreatment. 5. In 12 out of 19 cases in which a contra cutaneous reflex was conditioned by a stimulus to the ipsi flank skin nerve (C-T 30 ms), the number of discharges in the early peak of the histogram was less than that in the early peak of the histogram derived from the unconditioned contra response, independent of estrogen pretreatment. 6. Intravenous injections of progesterone (P) or its metabolite 5 alpha-pregnane-3 alpha-ol-20-one (tetrahydraprogesterone, THP) decreased the magnitude of the early peak of the ipsi cutaneous reflex and the contra cutaneous reflex in LL, independent of estrogen pretreatment. At the same time, it did not reduce the magnitude of the early peak evoked by either ipsi or contra nerves after conditioning from the other side at C-T 30 ms. 7. As a consequence, the percentage facilitation of ipsi cutaneous reflexes by contra cutaneous conditioning was significantly increased after P or THP. This suggests that these steroids can selectively enhance behaviors involving bilateral inputs. 8. An unchanged axial motoneuron pool output to bilateral cutaneous inputs after P and THP, in spite of reduced motoneuron responses to cutaneous inputs from each side of the body, implies an increased gain in the reflex circuit.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230929 TI - Motoneuron and muscle-unit properties after long-term direct innervation of soleus muscle by medial gastrocnemius nerve in cat. AB - 1. This study addresses the following questions. 1) In a previous experiment, when the combined lateral gastrocnemius-soleus nerve was cross-innervated by the medial gastrocnemius (MG) nerve, was the predominance of slow muscle units in soleus muscle a result of selective routing of slow motor axons into soleus? 2) Is MG-nerve-induced conversion of soleus muscle fibers from slow to fast more complete at very long (18 mo vs. 9-11 mo) postoperative times? 3) Do MG motoneurons that cross-innervate soleus muscle recover their normal membrane electrical properties at very long postoperative times? 2. The proximal portion of approximately one-third of the MG nerve was coapted directly with the distally isolated soleus nerve. The MG muscle remained innervated by the unoperated portion of the MG nerve. At 6, 10, or 18 mos postoperative, motoneuron and/or muscle-unit properties were determined for MG motoneurons innervating MG, soleus, or neither muscle, and for axotomized soleus motoneurons. 3. In the partially denervated MG muscle, the proportions of motor units of each type were normal. This suggests that the population of MG motor axons that had been directed to the soleus nerve also contained a representative distribution of MG motoneuron types. 4. Most motor units (74%) in cross-innervated soleus (Xsoleus) were type S (based on muscle-unit contractile properties), in spite of the soleus nerve's having been cross-connected by approximately 75% fast MG motoneurons. Thus, even at very long postoperative times, slow soleus muscle units resisted conversion by fast MG motoneurons. 5. Thirty-two percent of MG motoneurons that had been cross connected to soleus nerve elicited no measurable muscle contraction, compared with approximately 10% in previous reinnervation experiments in which the MG nerve was coapted with the MG or lateral gastrocnemius-soleus nerve. Thus MG motoneurons may be disadvantaged in their ability to innervate soleus muscle fibers. 6. It appears that at long postoperative times, those fast MG motoneurons tha had innervated large soleus muscle units had failed to convert those muscle fibers to fast types and had failed also to recover their normal motoneuron electrical properties. Conversion and recovery did occur for fast MG motoneurons that innervated small soleus muscle units and for slow MG motoneurons. PMID- 2230930 TI - Forcing of coupled nonlinear oscillators: studies of intersegmental coordination in the lamprey locomotor central pattern generator. AB - 1. This paper reports the results of an investigation of the basic mechanisms underlying intersegmental coordination in lamprey locomotion, by the use of a combined mathematical and biological approach. 2. Mathematically, the lamprey central pattern generator (CPG) is described as a chain of coupled nonlinear oscillators; experimentally, entrainment of fictive locomotion by imposed movement has been investigated. Interpretation of the results in the context of the theory has allowed conclusions to be drawn about the nature of ascending and descending coupling in the lamprey spinal CPG. 3. Theory predicts and data show that 1) the greater the number of oscillators in the chain, the smaller is the entrainment frequency range and 2) it is possible to entrain both above and below the rest frequency at one end but only above or below at the other end. 4. In the context of the experimental results, the theory indicates the following: 1) ascending coupling sets the intersegmental phase lags, whereas descending coupling changes the frequency of the coupled oscillators; 2) there are differences in the ascending and descending coupling other than strength; and it also suggests that 3) coupling slows down the oscillators. PMID- 2230931 TI - Azimuthal sensitivity of neurons in primary auditory cortex of cats. I. Types of sensitivity and the effects of variations in stimulus parameters. AB - 1. Preliminary to studying the organization of azimuthal sensitivity of neurons along frequency-band strips in the primary auditory cortex (AI) of cat (see companion paper), this study examined the sensitivity of 251 units in cat AI to variations in the azimuthal location of sound sources in the frontal hemifield. Most units (231) were tested with tones at the characteristic frequency (CF; frequency to which the unit had the lowest threshold). Unit CFs ranged from 5 to 36 kHz. A large number of units (91) were tested with broadband noise stimuli, and a few units were also tested at other frequencies within the cell's tuning response area. 2. When tested at stimulus intensities 20-30 dB above CF or noise threshold, the different forms of azimuthal sensitivity exhibited by AI neurons could be divided into (1) contra-field azimuth functions; (2) ipsi-field functions; (3) central-field functions; (4) omnidirectional functions, and (5) multipeaked functions. Contra-field azimuth functions were the most prevalent, with 45.9% of units tested with CF tones and 42.9% of units tested with noise exhibiting this type of azimuthal sensitivity. Ipsi-field azimuthal sensitivity was found in 16.9% of units tested with CF tones and 19.8% of units tested with noise. Central-field azimuthal sensitivity was seen in 10.8% of units tested with CF tones and 17.6% of units tested with noise. Omnidirectional azimuthal sensitivity was seen in 19.9% of units tested with CF tones and 17.6% of units tested with noise, whereas multipeaked azimuthal sensitivity was found in 6.5% of units tested with CF tones and 5.5% of units tested with noise. 3. The effects of increasing stimulus intensity on azimuthal sensitivity were examined in 185 units tested with CF tones and 67 units tested with noise. For four major classes of azimuthal sensitivity (contra-field, ipsi-field, central-field and omnidirectional), the most common effect (approximately 60% of each class) was for the azimuth function to remain constant in form by the defining criteria for these classes. The next most common effect for all classes except omnidirectional azimuth functions was for an expansion of the azimuthal range eliciting responses. (The definition of omnidirectionality precluded any expansion of the response range in this class of azimuth function). A smaller number of units in some classes showed a compression of the azimuth function to a smaller response range, and others showed more complex expansive and compressive effects with increasing stimulus intensity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230932 TI - Azimuthal sensitivity of neurons in primary auditory cortex of cats. II. Organization along frequency-band strips. AB - 1. The organization of azimuthal sensitivity of units across the dorsoventral extent of primary auditory cortex (AI) was studied in electrode penetrations made along frequency-band strips of AI. Azimuthal sensitivity for each unit was represented by a mean azimuth function (MF) calculated from all azimuth functions obtained to characteristic frequency (CF) stimuli at intensities 20 dB or more greater than threshold. MFs were classified as contrafield, ipsi-field, central field, omnidirectional, or multipeaked, according to the criteria established in the companion paper (Rajan et al. 1990). 2. The spatial distribution of three types of MFs was not random across frequency-band strips: for contra-field, ipsi field, and central-field MFs there was a significant tendency for clustering of functions of the same type in sequentially encountered units. Occasionally, repeated clusters of a particular MF type could be found along a frequency-band strip. In contrast, the spatial distribution of omnidirectional MFs along frequency-band strips appeared to be random. 3. Apart from the clustering of MF types, there were also regions along a frequency-band strip in which there were rapid changes in the type of MF encountered in units isolated over short distances. Most often such changes took the form of irregular, rapid juxtapositions of MF types. Less frequently such changes appeared to show more systematic changes from one type of MF to another type. In contrast to these changes in azimuthal sensitivity seen in electrode penetrations oblique to the cortical surface, much less change in azimuthal sensitivity was seen in the form of azimuthal sensitivity displayed by successively isolated units in penetrations made normal to the cortical surface. 4. To determine whether some significant feature or features of azimuthal sensitivity shifted in a more continuous and/or systematic manner along frequency-band strips, azimuthal sensitivity was quantified in terms of the peak-response azimuth (PRA) of the MFs of successive units and of the azimuthal range over which the peaks occurred in the individual azimuth functions contributing to each MF (the peak-response range). In different experiments shifts in these measures of the peaks in successively isolated units along a frequency-band strip were found generally to fall into one of four categories: 1) shifts across the entire frontal hemifield; 2) clustering in the contralateral quadrant; 3) clustering in the ipsilateral quadrant; and 4) clustering about the midline. In two cases more than one of these four patterns were found along a frequency-band strip.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230933 TI - Event-related potentials in the retina and optic tectum of fish. AB - 1. Compound field potentials were recorded with up to 18 microelectrodes in comb, brush, or spear arrays on and in the optic tectum and with suction electrodes from the distal stump of the cut optic nerve and from the optic nerve head in the opened eye in elasmobranchs and teleosts. Diffuse light flashes of different durations and submaximal intensities were delivered in trains with regular or irregular interstimulus intervals (ISI). 2. Event-related potentials (ERPs) are visible in single trials and begin at 50-200 ms after an "oddball" flash, especially one that is slightly weaker, briefer, or delayed by as little as 6% of ISI, compared with the more frequent stimulus. ERPs to the opposite condition are not of the same form or size. 3. One or more stimuli were omitted from a train or the train terminated after various conditioning times. Deflections occur beyond the expected visual-evoked potentials (VEPs) to the last flash and are called omitted-stimulus potentials (OSPs). They occur on schedule--approximately 100 ms after the next flash would be due--almost independent of intensity, duration, or conditioning time. They are considered to be ERPs without any necessary implication or denial of a temporally specific expectation. 4. Three components of OSP occur alone or in combination: an initial fast peak, a slow wave, and an oscillatory spindle up to ls or more in duration. This resembles the OFF response to steady light. 5. All these components are already present in the retina with optic nerve cut. 6. The same mean ISI with a high proportion of jitter gives OSPs with only slightly longer latencies and smaller amplitudes; the OSP acts as though the retina makes an integrated prediction of ISI, intensity, and duration. 7. During a conditioning train the equilibrium between excitation and inhibition after each flash changes according to frequency, intensity, duration, and conditioning time; the VEP reflects this in a shape unique to the ISI; inhibition increases rapidly after each flash and then decays slowly according to the recent mean ISI. This allows rebound disinhibition after missing, weak, or delayed flashes (OSP or ERP) or causes an altered VEP after a longer or stronger oddball. 8. It seems unlikely that the OSP or oddball ERP in fish tectum is equivalent to mammalian ERPs under the same regime or signals higher cognitive events, because they are already present in the retina, require flash frequencies greater than 1 Hz, and grow with frequency up to and beyond flicker fusion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230934 TI - Effect of bilateral auditory cortex lesions on sound localization in Japanese macaques. AB - 1. The ability of four Japanese macaques (Macaca fuscata) to localize sound was determined after bilateral ablation of auditory cortex. The animals were given two tests: a "midline" test in which they had to discriminate noise bursts presented from a loudspeaker located to the left from identical noise bursts presented from a loudspeaker located to the right of midline, and a "hemifield" test in which both loudspeakers were located in their right hemifield. 2. Both of the tests were administered by the use of two different behavioral tasks: a conditioned-avoidance task in which the animals were trained to make or break contact with a water spout to indicate the location of a sound source, and a two choice task that required the animals to walk to the source of the sound. 3. The results of both the conditioned-avoidance and the two-choice tasks demonstrated that the animals were able to perform the midline discrimination although their localization acuity was reduced. However, the animals had great difficulty in learning to walk to the source of a sound in spite of the fact that they had received previous sound-localization training in the conditioned-avoidance task. This difficulty suggested that the monkeys no longer associated the sound with a location in space. 4. The results of both the conditioned-avoidance and the two choice tasks demonstrated that the animals were unable to discriminate the locus of a sound source when both loudspeakers were located in the same hemifield. 5. Bilateral ablation of auditory cortex results in both sensory and perceptual deficits. The presence of sensory deficits is indicated by the decreased acuity in the left-right discrimination and the inability to discriminate between two loudspeakers located in the same hemifield. The deficit in the perception of the locus of sound is indicated by the difficulty in learning to approach the source of a sound, an ability which normal monkeys exhibit without training. 6. There appear to be species' differences in the effect of auditory cortex lesions on sound localization. Although cortical lesions result in a sound-localization deficit in several species of primates and carnivores, they have little or no effect on rats. PMID- 2230935 TI - Intracellular responses of identified rat olfactory bulb interneurons to electrical and odor stimulation. AB - 1. Intracellular recordings were made from 28 granule cells and 6 periglomerular cells of the rat olfactory bulb during odor stimulation and electrical stimulation of the olfactory nerve layer (ONL) and lateral olfactory tract (LOT). Neurons were identified by injection of horseradish peroxidase (HRP) or biocytin and/or intracellular response characteristics. Odorants were presented in a cyclic sniff paradigm, as reported previously. 2. All interneurons could be activated from a wide number of stimulation sites on the ONL, with distances exceeding their known dendritic spreads and the dispersion of nerve fibers within the ONL, indicating that multisynaptic pathways must also exist at the glomerular region. All types of interneurons also responded to odorant stimulation, showing a variety of responses. 3. Granule cells responded to electrical stimulation of the LOT and ONL as reported previously. However, intracellular potential, excitability, and conductance analysis suggested that the mitral cell-mediated excitatory postsynaptic potential (EPSP) is followed by a long inhibitory postsynaptic potential (IPSP). An early negative potential, before the EPSP, was also observed in every granule cell and correlated with component I of the extracellular LOT-induced field potential. We have interpreted this negativity as a "field effect," that may be diagnostic of granule cells. 4. Most granule cells exhibited excitatory responses to odorant stimulation. Odors could produce spiking responses that were either nonhabituating (response to every sniff) or rapidly habituating (response to first sniff only). Other granule cells, while spiking to electrical stimulation, showed depolarizations that did not evoke spikes to odor stimulation. These depolarizations were transient with each sniff or sustained across a series of sniffs. These physiological differences to odor stimulation correlated with granule cell position beneath the mitral cell layer for 12 cells, suggesting that morphological subtypes of granule cells may show physiological differences. Some features of the granule cell odor responses seem to correlate with some of the features we have observed in mitral/tufted cell intracellular recordings. Only one cell showed inhibition to odors. 5. Periglomerular (PG) cells showed a response to ONL stimulation that was unlike that found in other olfactory bulb neurons. There was a long-duration hyperpolarization after a spike and large depolarization or burst of spikes (20 30 ms in duration). Odor stimulation produced simple bursts of action potentials, Odor stimulation produced simple bursts of action potentials, suggesting that PG cells may simply follow input from the olfactory nerve.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230936 TI - Induction of long-term potentiation at hippocampal mossy-fiber synapses follows a Hebbian rule. AB - 1. The induction of long-term potentiation (LTP) at hippocampal mossy-fiber synapses requires an increase in postsynaptic [Ca2+]i but is independent of N methyl-D-aspartate (NMDA) receptor activation. Voltage-gated Ca2+ channels have been proposed as one alternative source for raising [Ca2+]i during the induction of LTP. We tested the hypothesis that voltage-gated Ca2+ channel activation could mediate the induction of LTP by examining whether 1) the induction of mossy-fiber LTP was dependent on postsynaptic depolarization and 2) depolarization alone, of a magnitude presumably capable of activating Ca2+ channels, was sufficient to induce LTP. 2. Intracellular recordings were made from rat CA3 pyramidal cells in the hippocampal slice preparation under both current- and voltage-clamp conditions. Mossy-fiber postsynaptic potentials and currents were recorded before and after high-frequency stimulation (HFS) in the presence of 20-50 microM D-2 amino-5-phosphonovaleric acid (D-APV), an NMDA-receptor antagonist. 3. Voltage clamping of CA3 neurons between -80 and -100 mV during HFS reversibly blocked the induction of mossy-fiber LTP. Conversely, HFS paired with depolarizing-current steps under current clamp increased the magnitude of LTP compared with controls. These results indicate that mossy-fiber LTP is dependent on postsynaptic depolarization, and presynaptic activation alone was not sufficient to induce mossy-fiber LTP. 4. Depolarizing-current injections, which presumably depolarized CA3 cells to potentials sufficient to activate voltage-gated Ca2+ channels, had no effect on mossy-fiber synaptic responses. These results suggest that synaptic activation, in addition to postsynaptic depolarization, is required for the induction of mossy-fiber LTP. 5. Single mossy-fiber afferent volleys were also paired with depolarizing-current pulses. In the presence of APV, pairing of single-mossy-fiber excitatory postsynaptic potentials (EPSPs) with postsynaptic depolarization did not potentiate synaptic responses, suggesting that some form of HFS is also required for mossy-fiber LTP. In the absence of APV, however, the contamination of mossy-fiber synaptic responses by CA3-recurrent inputs resulted in some potentiation. 6. These results suggest that the induction of mossy-fiber LTP is dependent on both pre- and postsynaptic activity and thus follows a Hebbian rule for synaptic modification. In contrast to that demonstrated at Schaffer-collateral-commissural synapses, however, the induction of mossy-fiber LTP may require HFS in addition to postsynaptic depolarization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2230937 TI - GABA actions within the caudal cochlear nucleus of developing kittens. AB - 1. The effects of gamma-aminobutyric acid (GABA), microionophoretically applied onto neurons within the dorsal and posteroventral divisions (i.e., caudal regions) of the cochlear nucleus (CN), were studied during postnatal development in kittens with the use of extracellular recording techniques. Approximately 80% of all neurons encountered within the caudal CN responded to exogenously applied GABA regardless of neuronal response type or postnatal age. 2. GABA reduced acoustically evoked as well as spontaneous discharge rates in a dose-dependent manner at all ages studied, and generally abolished discharge activity at sufficiently high doses (i.e., ejection currents). Dose-response curves generated during acoustic stimulation by varying GABA ejection current were sigmoidal at all ages studied, and the range of slopes relating discharge rate to applied currents increased during the first 10 postnatal days. 3. Neural thresholds to acoustic stimuli were elevated, and slopes of discharge-rate-versus-sound pressure-level curves were depressed regardless of age when GABA was microionophoresed onto CN neurons. 4. GABA's capacity to reduce spontaneous or acoustically evoked discharge rates was a voltage-dependent phenomenon directly related to control discharge rates (i.e., efficacy was high when discharge rates were high) for neurons recorded from both immature and mature animals. 5. A small set of neurons recorded from animals younger than 2 wk exhibited prolonged GABA "activation" and "deactivation" times (i.e., times required to achieve 90% of the maximal effect evoked by GABA and to recover from that effect, respectively) and may represent a group of actively differentiating units. 6. Bicuculline microionophoresis effectively blocked the actions of exogenously applied GABA and endogenous GABA, which, presumably, was synaptically released as a result of acoustic stimulation. The actions of bicuculline were dose dependent in animals ranging in age from 2 postnatal days to adulthood. These results suggest that recognition sites for GABA and bicuculline and the ionophore associated with the GABA receptor are present and functionally coupled in the caudal CN before the developmental period during which the full complement of inhibitory projections form synaptic contacts with these cells. PMID- 2230938 TI - Human platelets contain brain-derived neurotrophic factor. AB - Neurotrophic support to peripheral sensory neurons is provided by 2 factors of related sequence, NGF and brain-derived neurotrophic factor (BDNF). NGF is present in peripheral target tissues, while BDNF has only been reported in the CNS. We now report the biological characterization and molecular cloning of a cDNA for BDNF from human platelets. BDNF in human platelets has biological activities very similar to those of BDNF obtained from adult porcine brain in neuron-enriched cultures prepared from peripheral ganglia of chick embryos at 8 12 d of incubation. BDNF from human platelets promoted the survival and neurite outgrowth of placodal and neural crest-derived sensory neurons, but not to parasympathetic or sympathetic neurons. Activity of the factor was additive to that of NGF in dorsal root ganglia (DRG) neuron cultures and is equivalent to porcine brain BDNF in nodose ganglion neuron cultures. On SDS-PAGE, BDNF from human platelets is recovered at an apparent molecular weight equivalent to porcine brain BDNF (13,000 D). A BDNF cDNA fragment was amplified from human platelet RNA by using a coupled reverse transcriptase-polymerase chain reaction. Molecular cloning and DNA sequence analysis of the amplified cDNA fragment revealed complete identity for the deduced amino acid sequences of human and porcine BDNF [amino acid (aa) 10-108 of the mature factor]. Thus, human platelets might provide an important source of BDNF for regenerating peripheral sensory neurons at the site of nerve injury. PMID- 2230939 TI - Amygdalar interaction with the mediodorsal nucleus of the thalamus and the ventromedial prefrontal cortex in stimulus-reward associative learning in the monkey. AB - Cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to associate visual stimuli with food reward. They learned a series of new 2-choice visual discriminations between colored patterns displayed on a monitor screen. The feedback for correct choice was the delivery of food. In order to promote associative learning between the visual stimuli and the incentive value of the food reward, reward delivery was not accompanied by any distinctive visual feedback on the display screen. The rate of learning new problems was assessed before and after surgery in a total of 16 monkeys. Three groups of 3 monkeys received bilaterally symmetrical ablations in either the amygdala, the mediodorsal nucleus of the thalamus, or the ventromedial prefrontal cortex. All these groups showed a severe postoperative learning impairment. Seven other animals were given a unilateral ablation in 1 of those 3 structures and a second unilateral ablation, in each case contralateral to and different from the first, in order to produce 2 groups in which a putative amygdalo-thalamo-prefrontal pathway had been disconnected by crossed unilateral lesions. One disconnection group had lesions in the amygdala and ventromedial prefrontal cortex; the other had lesions in the amygdala and the mediodorsal nucleus of the thalamus. The disconnection groups showed a significant impairment, but the effect of the disconnection surgeries was significantly milder than the effect of any of the 3 bilaterally symmetrical lesions. Therefore, symmetrical bilateral lesions in either the amygdala, the mediodorsal nucleus, or the ventromedial prefrontal cortex produce similar impairments in the present task, implying that these structures are functionally related to each other; but the relatively mild effect of disconnecting these structures from each other argues against the hypothesis that they are serial stages in a single, tightly linked functional pathway. PMID- 2230940 TI - Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines. AB - In previous studies, it has been demonstrated that ciliary neurotrophic factor (CNTF) has a potent survival effect on various populations of neurons in culture, in particular, neurons isolated from chick ciliary, dorsal root sensory, and sympathetic ganglia (Barbin et al., 1984). After recent investigations demonstrated that CNTF prevents the degeneration of motoneurons in newborn rats after axonal lesion (Sendtner et al., 1990), the question arose as to whether CNTF also has a survival effect on embryonic chick motoneurons at the developmental stage where physiological cell death occurs. To study this, it was essential to develop an isolation and culture procedure for the survival of chick E6 spinal motoneurons in which non-neuronal cells were eliminated and the motoneurons were highly enriched. In these cultures, virtually all of the initially plated motoneurons survived for at least 3 d in the presence of muscle extract, which was chosen as a positive control. Retrograde labeling of the motoneurons prior to their isolation showed that there is more than an 80% enrichment for motoneurons by the method used. The retrogradely labeled neurons also fulfilled the morphological criteria (diameter of neurons, appearance of processes) to identify motoneurons independent of retrograde labeling. Under these conditions, CNTF at a concentration of 1.5 ng/ml (EC50, 0.023 ng/ml) supported maximally 64% of the initially plated spinal motoneurons after 3 d and 53% after 6 d (the longest time period investigated). Other neurotrophic factors, such as NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3, had no survival effect at all, even at concentrations up to 10 micrograms/ml for NGF and BDNF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2230941 TI - Motor nerve regulates muscle extracellular matrix proteoglycan expression. AB - Denervation of rat leg muscles caused a 2-3-fold increase in 35S-sulfate and 3H glucosamine incorporation into proteoglycans of the muscle extracellular matrix. The size of the proteoglycans and the glycosaminoglycan chain length and degree of sulfation were unchanged. Because the rate of degradation of proteoglycans was also unchanged by denervation, we infer that denervation increases proteoglycan synthesis. Muscle reinnervation restored the original rate of synthesis of proteoglycans. Paralysis of innervated muscle caused increased incorporation of sulfate comparable to that seen in denervation. Thus motor nerve activity appears to regulate the level of proteoglycans in the muscle extracellular matrix. PMID- 2230943 TI - Hippocampal representation in place learning. AB - The generality of the place-learning impairment associated with hippocampal system damage was challenged using methods of training that permitted subjects to form an individual association between the place of escape and a particular navigational route in an open-field water maze. Both normal rats and rats with fornix lesions (FX rats) acquired this task rapidly, although FX rats were slightly slower in achieving minimum escape latencies. In postcriterion testing, FX rats occasionally made near misses but, more often, their escape performance was indistinguishable from that of intact rats. Results from a variety of probe tests indicated that FX rats, like normal rats, had based their performance on a representation of multiple distal cues but their representation, unlike that of normal rats, was inflexible in that it could not be used to guide performance when the cues or starting position were altered. These results parallel those from other studies of hippocampal function in animals and humans: The learning deficit consequent to hippocampal system damage (1) is not specific to a particular category of learning materials, but is dependent on the representational demands of the task; (2) is observed when task demands encourage a representation based on relations among multiple cues, but not when the task encourages adaptation to an individual (or compound) stimulus; (3) spares acquisition of fundamental procedures needed to perform the task; and (4) impairs the flexible use of learned information in tests other than repetition of the learning experience. PMID- 2230942 TI - Opiate antagonist nalmefene improves intracellular free Mg2+, bioenergetic state, and neurologic outcome following traumatic brain injury in rats. AB - Treatment of CNS trauma with the opiate antagonist naloxone improves outcome, though the mechanisms of action remain speculative. Nalmefene is another opiate receptor antagonist, but it has substantially greater potency and duration of action than naloxone. It also has increased activity at kappa opiate receptors and has recently been shown to limit histological changes and neurological dysfunction after traumatic spinal cord injury. The present study examined the effects of treatment with nalmefene on outcome after fluid-percussion-induced traumatic brain injury in rats, using magnetic resonance spectroscopy to monitor acute metabolic changes and behavioral tests to determine chronic neurological recovery. Single-dose treatment with nalmefene (100 micrograms/kg, i.v.) at 30 min after trauma significantly improved (p less than 0.05) neurological outcome (up to 4 weeks) as compared to saline-treated controls. Early changes in intracellular free-magnesium concentration, adenosine diphosphate concentration, and cytosolic phosphorylation potential were all significantly improved by nalmefene treatment, reflecting improved bioenergetic state. We suggest that the ability of nalmefene to improve cellular bioenergetics after trauma may in part account for the neuroprotective effects of this and related compounds. PMID- 2230944 TI - How well do response changes of striate neurons signal differences in orientation: a study in the discriminating monkey. AB - Just-noticeable differences (JNDs) in orientation were measured in 2 monkeys using a temporal same-different task, with stationary rectangular gratings as stimuli, and compared to those of humans tested in the same setup. The JNDs of one monkey (1.5 degree) were similar to those of humans; those of the other monkey were larger (5.8 degrees). We recorded from V1 neurons in these monkeys while they were performing the orientation discrimination with the same stimuli and under the same conditions as used in the behavioral testing. In order to determine how small a difference in orientation the V1 neurons can, in these conditions, signal reliably by small changes in firing rate, we performed 2 different receiver-operating characteristic (ROC) analyses. One ROC analysis was performed on the number of spikes evoked by the first of the 2 stimulus presentations as a function of the orientation of this stimulus. Neural JNDs derived from the neurometric curve were obtained in this way for 50 cells. In the second ROC analysis, the difference in the number of spikes evoked by the 2 stimuli presented in succession during 1 trial was analyzed as a function of orientation difference between the 2 stimuli. Neural JNDs were obtained by this procedure for 21 cells. These 2 complementary ROC analyses yielded very similar results. Also, the results were similar for the 2 monkeys. A minor fraction of V1 cells can reliably signal difference in orientation as small as 2.5 degrees, but none could signal differences smaller than 2 degrees. Our results also showed that the neural JND obtained by the ROC analysis depends on the duration of the interval during which spikes are counted. In these experiments, this duration could be chosen rather precisely, because the reaction times of the 2 monkeys were measured. Also, our results showed that the neural JND depends on the point of the tuning curve at which the measurement is made and is smallest when this is done on the steepest part of the tuning curve. Finally, our results show that the discriminative capacity of V1 neurons does not depend so much on each of the tuning characteristics--bandwidth, response strength, and variability--as on the combination of these factors. PMID- 2230945 TI - Retrosplenial cortex: possible role in habituation of the orienting response. AB - A patient with a unilateral lesion that included the retrosplenial area had a propensity to attend to contralateral stimuli. To determine whether the retrosplenial-area lesion was inducing this defect, unilateral retrosplenial lesions were produced in rats by surgical aspiration. Animals were assessed preoperatively and postoperatively for orientation and habituation to bilateral simultaneous stimulation in 3 sensory modalities: visual, tactile, and auditory. At each session, the orientation test was terminated upon completion of 5 trials per modality, and the habituation test ended after 4 consecutive response failures or upon completion of 15 trials per modality. Postoperatively, contralateral orientation was not significantly different from ipsilateral orientation, suggesting that there was no neglect. However, there was a significant delay in habituation to contralateral stimulation in postoperative weeks 2 and 3-5. Our results suggest that rats with retrosplenial area lesions have normal orientation but fail to habituate to contralateral stimuli. PMID- 2230946 TI - The distribution of free calcium in transected spinal axons and its modulation by applied electrical fields. AB - Intracellular free-calcium concentration ([Ca2+]i) was measured in lamprey spinal axons using the fluorescent calcium indicator fura 2. We used both a photomultiplier tube and a video-image processing system to measure the temporal and spatial distributions of [Ca2+]i in the proximal segments of transected axons. Within 3 min following transection, a spatially graded increase in the [Ca2+]i was apparent in the last few millimeters of the axons. Superimposed on the initial gradient was a moving front of calcium that progressed up the axon, reaching 1.6 mm from the cut end in 3 hr. The [Ca2+]i behind the moving front exceeded 10 microM. This movement of Ca2+ was greatly reduced by an externally applied electrical field with the cathode distal to the lesion and was increased by an applied field of the opposite polarity. When axons were transected in Ca2(+)-free medium, no increases in [Ca2+]i occurred. One d after transection, [Ca2+]i was at or below the precut levels, except in the distal 250 microns, where it remained slightly elevated. Therefore, axons can survive the high levels of [Ca2+]i that occur after transection and can reestablish normal [Ca2+]i levels within 24 hr. Measurements of both the diffusion coefficient and the fluorescence polarization of fura 2 indicate that the dye is not significantly bound to axoplasmic components. PMID- 2230947 TI - Changes in instrumentally and classically conditioned limb-flexion responses following inferior olivary lesions and olivocerebellar tractotomy in the cat. AB - Lesions were placed in various parts of the inferior olivary nucleus and olivocerebellar tract in an attempt to define further the role of the inferior olive in the performance of a conditioned limb-flexion response (LFR) in cats. Thirty-two cats were trained to make an LFR using either classical or instrumental conditioning. The conditioned stimulus (CS) was a tone, and the unconditioned stimulus (US), a shock to the forelimb. Following training, lesions were placed in various parts of the inferior olivary nucleus in 20 animals (radio frequency lesions, 17; electrolytic lesions, 3). Midline section of the olivocerebellar tract was carried out in 12 animals. The degree of conditioned response (CR) loss resulting from a given lesion was closely related to the precise locus of the lesion. Rostromedial olivary lesions, which included the spino- and cortico-olivary forelimb projection zones and the olivocerebellar projection area, resulted in varying degrees of CR loss (from partial to near total), deregulation of response latency, and a significant reduction of response amplitude. The CR deficit and degree of post-operative CR recovery were directly related to the extent of damage to this part of the rostromedial olive. Lesions restricted to the caudal olive or to caudal levels of the olivo-cerebellar tract resulted in no postoperative CR deficits. Animals with caudal lesions, however, showed more severe general motor deficits postoperatively than did those with rostromedial lesions and loss of the CR. Prolonged training of animals with the most complete CR deficits resulted in some relearning, but response patterns were typified by long-latency, low-amplitude CRs and a highly unstable response pattern. PMID- 2230948 TI - Inhibition of neurite outgrowth on astroglial scars in vitro. AB - Traumatic injury to the adult mammalian CNS results in the formation of an astroglial-mesenchymal scar that seals the wound site but blocks axonal regeneration in the process. The mechanism that leads to this inhibition of axon outgrowth has been proposed to be either a physical barrier blocking the advancement of the growth cone or chemical factors actively inhibiting axon outgrowth. At present, it is unknown whether one or both of these mechanisms are responsible for the inhibitory nature of the glial scar in vivo. Using a model of CNS trauma that allows for removal of an adult rat glial scar intact on a nitrocellulose support and placement in vitro with the upper surface exposed, we addressed the question of whether the inhibitory effects could be accounted for by chemical components at the scar surface. A purified population of rat hippocampal neurons was seeded onto the scar explants as well as onto explants taken from neonatal rat cerebral cortex, and the extent of neurite outgrowth was compared. We found that the glial scar, at best, stimulates only minimal neurite outgrowth over its surface when compared to the immature environment explanted in the same manner. This growth-inhibitory state cannot merely be explained by neuronotoxic factors or fibroblasts preventing astrocyte-mediated neurite outgrowth. The inhibition is more probably due to the expression of molecules on the surface of the adult scar that either directly inhibit growth cones or inhibit them indirectly by occluding neurite-promoting factors in the extracellular matrix or on the astrocyte surface. PMID- 2230949 TI - Nerve growth factor infusion in the primate brain reduces lesion-induced cholinergic neuronal degeneration. AB - NGF is a protein that promotes survival, differentiation, and process extension of selected neuronal populations during development and, in some cases, in the mature organism. Previous lesion and aging studies in the rat have shown that intracerebroventricular NGF infusions can prevent degenerative changes in basal forebrain cholinergic neurons. We sought to determine whether salutory effects of NGF occur in the primate brain. Cholinergic fibers of the septohippocampal projection in the primate were surgically transected, followed by infusion of either a vehicle or an NGF solution into the ventricular system for a 4-week period. Quantification of cholinergic neurons in the medial septal nucleus at the end of the infusion period demonstrated that only 45 +/- 5% of cholinergic neurons could be identified after fornix lesions in vehicle-infused animals, whereas 80 +/- 6% of neurons were visible in NGF-treated animals. Thus, NGF substantially reduced lesion-induced cholinergic neuronal degeneration in the adult primate brain. This finding may be relevant to the hypothesis that NGF has potential use as a cholinergic "neurotrophic-factor therapy," given that loss of basal forebrain cholinergic neurons is common in Alzheimer's disease. PMID- 2230950 TI - Development of the retinotectal projection in zebrafish embryos under TTX-induced neural-impulse blockade. AB - The influence of neural activity on the morphology of retinal-axon-terminal arbors and the precision of the developing retinotectal projection in zebrafish embryos was explored. Terminal-arbor morphology and their distribution in the tectum was determined with anatomical fiber-tracing methods using the fluorescent dyes dil and diO. To allow development under activity-deprived conditions, TTX was injected into the eyes of 30-38-hr-old zebrafish embryos at concentrations that effectively blocked neural activity both in retinal ganglion cells and throughout the CNS. Much like axons with normal neural-activity patterns, activity-deprived axons from dorsal and ventral and from temporal and nasal regions in the retina terminated over retinotopically appropriate and nonoverlapping regions of the tectum. Even after ablation of 1 hemiretina at the time of axonal outgrowth, activity-deprived axons from the remaining hemiretina grew directed toward and arborized selectively within their retinotopically appropriate tectal half in the same way as would nondeprived axons. Besides being retinotopic, the area over which small populations of activity-deprived axons from neighboring ganglion cells arborize is as small as that of active axons. The size of terminal arbors of retinal ganglion cell axons was unaffected by blockade of neural activity. The mean terminal-arbor size was 27 x 18 microns for the TTX injected and 31 x 22 microns for the control embryos. The tectal coverage of TTX blocked and control axons was equally small, with values of 1.4% and 1.6%, respectively. These data show that a precisely organized retinotopic map in developing zebrafish forms independent of neural-impulse activity. PMID- 2230951 TI - Inhibition of Schwann cell myelination in vitro by antibody to the L1 adhesion molecule. AB - The specific axonal and Schwann cell surface molecules that mediate the initiation of myelination have not been identified. We have used cocultures of purified rat dorsal root ganglion neurons and Schwann cells and purified polyclonal antibodies to the L1 adhesion molecule to study the role of L1 in myelin formation. Schwann cells were first arrested in a basal-lamina-free premyelination stage (by serum/ascorbate deprivation), then manipulated to allow basal lamina deposition and myelination (by serum/ascorbate addition) in the absence or presence of anti-L1. Using electron microscopy, immunocytochemistry, and myelin sheath quantitation after Sudan-black staining, we determined the effect of anti-L1 on (1) basal lamina formation, (2) the segregation by Schwann cells of axons into a 1:1 relationship, (3) galactocerebroside (Gal-C) expression, (4) laminin deposition, and (5) myelin formation. Anti-L1 strongly blocked myelin formation, Gal-C expression, and axon segregation but did not block basal lamina formation. In controls, elongated Schwann cell processes completely covered the axons and exhibited uniform surface staining for laminin; in anti-L1-treated cultures, shortened Schwann cells, intensely stained for laminin, were observed in clusters separated by unstained lengths of axons. When 50 micrograms/ml exogenous purified laminin was added to the medium, Schwann cell length and laminin staining were similar in control and treated cultures. However, the inhibition of myelination of anti-L1 was not altered by the addition of laminin. Myelination was also inhibited with antigen-binding fragments (Fab) of polyclonal anti-L1, but an antibody to liver membranes did not block myelination. These results indicate that L1 is involved in the linear extension of Schwann cell processes along axons, the engulfment of axons, and the induction of myelin-specific components within the Schwann cell. We conclude that anti-L1 prevents myelination by blocking these events rather than by blocking basal lamina deposition. PMID- 2230952 TI - Serotonin synthesis and distribution in Drosophila dopa decarboxylase genetic mosaics. AB - In Drosophila, the enzyme dopa decarboxylase (DDC) catalyzes the last step in the biosynthesis of serotonin (5HT) and dopamine. In the present study, the distribution of DDC and one of its biosynthetic products (5HT) was determined in CNSs that were genetic mosaics, composed of neurons that have DDC activity and neurons that lack DDC activity. Phenotypic mosaicism, that is, immunoreactive (IR) and non-IR neurons within the same nervous system, was observed for both DDC and 5HT immunoreactivity. DDC-IR neurons were always 5HT-IR, but some 5HT-IR neurons devoid of DDC immunoreactivity were also observed. 5HT-IR neurons devoid of DDC immunoreactivity were always in close apposition to other DDC-IR neurons. We suggest that in vivo uptake mechanisms are responsible for 5HT accumulation in neurons devoid of DDC immunoreactivity. PMID- 2230953 TI - Circadian timekeeping in BALB/c and C57BL/6 inbred mouse strains. AB - Circadian rhythms of locomotion (wheel-running activity) in 12 inbred mouse strains were recorded for interstrain differences in tau DD, the endogenous (free running) period of the circadian pacemaker measured in constant environmental darkness. The results indicate that 1 or more genetic loci influence the value of tau DD, and a large (50 min) difference in mean tau DD between 2 of the strains, BALB/cByJ and C57BL/6J, allowed further characterization of the origins and inheritance of the polymorphic expression of this circadian pacemaker property. The interstrain difference in mean tau DD was associated with an interstrain difference in light-induced shifts of the phase of the free-running locomotor rhythm; the BALB/c strain (with the shorter mean tau DD) displayed relatively fewer advance phase shifts. Neither the history of previous light exposure, albinism, nor elevated circulating testosterone levels could account for the interstrain difference in mean tau DD. The value of tau DD based on the circadian rhythm of drinking activity (with the running wheel removed) was longer than that based on locomotion; this discrepancy was significantly greater and more variable in BALB/c than in C57BL/6 mice, though the interstrain difference in mean tau DD could not be attributed entirely to this effect. Reciprocal F1 hybrids of BALB/c x C57BL/6 matings revealed dominance of the C57BL/6 genotype, no sex linkage, and a significant (but small) maternal effect. Examination of CXB recombinant inbred strains provided no support for the hypothesis of monogenic inheritance. Further study of inherited differences in the BALB/c and C57BL/6 strains may be a useful noninvasive experimental approach for investigation of the neurobiological substrates of circadian rhythmicity. PMID- 2230954 TI - Brain IL-1-induced immunosuppression occurs through activation of both pituitary adrenal axis and sympathetic nervous system by corticotropin-releasing factor. AB - Intracerebroventricular infusion of femtomolar quantities of interleukin-1 (IL-1) or stimulated release of endogenous IL-1 in the brain suppresses various cellular immune responses, decreasing natural killer cell (NK) activity, response to mitogen, and interleukin-2 production of splenic and blood lymphocytes (an effect hereafter called "brain IL-1-induced immunosuppression"). The present study examines mechanisms by which IL-1 produces this effect. First, because IL-1 in the brain activates the pituitary-adrenal axis by stimulating release of corticotropin-releasing factor (CRF), the role of CRF was investigated. To block CRF, affinity-purified antibody to CRF was infused into the lateral ventricle 30 min before introduction of IL-1. When this was done, suppression of cellular immune responses that normally follow IL-1 infusion was completely prevented. Infusion with an equal quantity of non-CRF IgG prior to IL-1 was without effect. Second, the role of sympathetic nervous activity was examined. To block neural transmission at sympathetic ganglia, chlorisondamine (3.0 mg/kg) was injected intraperitoneally 60 min before IL-1 infusion. When this was done, suppression of immune responses by IL-1 was partially blocked. These results indicate that IL-1 in the brain suppresses various cellular immune responses by activating both the pituitary-adrenal axis and the sympathetic nervous system, and that these systems are both activated through the influence of IL-1 on CRF. PMID- 2230955 TI - Discrimination learning alters the distribution of protein kinase C in the hippocampus of rats. AB - Protein kinase C (PKC), an enzyme that plays an essential role in eukaryotic cell regulation (Nishizuka, 1988; Huang et al., 1989), is critical to memory storage processes both in the marine snail Hermissenda crassicornis and in the rabbit (Alkon et al., 1988; Bank et al., 1988; Olds et al., 1989). Specifically, activation of PKC mimics neurobiological correlates of classical conditioning in both Hermissenda and the rabbit, and the distribution of the enzyme within the rabbit hippocampus changes after Pavlovian conditioning. Here, we report that the amount of PKC, as assayed by specific binding of 3H-phorbol-12,13-dibutyrate (3H PDBU), decreased significantly within the hippocampal CA3 cell region in rats trained to solve a water maze task either by cognitive mapping or by visual discrimination strategies, but not in control rats. Furthermore, hippocampal lesions interfered with acquisition of both of these tasks. We interpret these findings to support the conclusion that distributional changes of PKC within the mammalian hippocampus play a crucial role in memory storage processes. PMID- 2230956 TI - Transfected rat high-molecular-weight neurofilament (NF-H) coassembles with vimentin in a predominantly nonphosphorylated form. AB - A fully encoding cDNA for the high-molecular-weight rat neurofilament protein (NF H) has been isolated from a lambda gt11 library, sequenced and subcloned into eukaryotic expression vectors. Sequence analysis shows that rat NF-H has an overall homology of 72 and 88% with human and mouse NF-H, respectively. The head and rod domains are almost entirely identical, and the divergences are due to differences in the long C-terminal extensions of the molecule. The consensus phosphorylation sequence for neurofilaments Lys-Ser-Pro (KSP) is present 52 times. The predicted molecular mass of the protein is 115 kDa, 42% lower than that observed by SDS-PAGE. Upon transfection into vimentin-containing fibroblasts, such as L tk-, L929, and 3T6 cells, NF-H is seen distributed with vimentin by light and electron microscopic examinations indicating that copolymers of NF-H and vimentin are formed in these cells. Only a negligible proportion of the cells is positive when stained with a number of antibodies directed against phosphorylated NF-H epitopes. This is in contrast with the middle molecular weight NF protein (NF-M) transfected into L tk- and L929 cells, which can readily be detected by antibodies against phosphorylated neurofilament epitopes. The mobilities of the transfected protein on 1- and 2-dimensional gels confirm that NF-H is predominantly in a nonphosphorylated form. These results indicate that phosphorylation of NF-H, but not NF-M, on the KSP sequence is due to protein kinases, which are not present in fibroblasts and are presumably NF-H specific. The stable NF-H-expressing cell lines can therefore be used to study these putative neurofilament kinases in vitro and in vivo. PMID- 2230957 TI - The visuotopic component of the multisensory map in the deep laminae of the cat superior colliculus. AB - A well-defined map of visual space is located in the deep laminae of the cat superior colliculus. The horizontal meridian is oriented rostral-caudal, while the vertical meridian is oriented perpendicular to it in the rostral third of the structure. This map represents the entire contralateral visual field and extends approximately 40 degrees into ipsilateral visual space. Although the deep-laminae visuotopy is similar to that found in the superficial laminae of the same structure, the topographic register among these maps is most secure rostrally but becomes increasingly poorer at more caudal and lateral locations. The combination of 2 features distinguish the deep-layer visual representation from that found in the superficial laminae and in geniculocortical systems: (1) the constituent visual receptive fields are very large (mean diameter, 66.9 degrees), and (2) the majority (greater than 70%) of the neurons composing it receive nonvisual inputs. Because the visual receptive fields of visual-multisensory neurons are significantly larger than those of neighboring neurons that respond only to visual stimuli, far more visual-multisensory neurons are activated by any given visual stimulus. These data, when coupled with those from previous studies, suggest that, from a functional perspective, deep-laminae visual neurons form one component of an integrated multisensory map, and that their topographic organization is essential for the normal dynamics of multisensory integration. PMID- 2230959 TI - Orthodontic application of proximal clasps. AB - Removable plates are widely used for various purposes in orthodontics. In order to accomplish the designed treatment objective, it is necessary to provide sufficient retention of the removable appliance. In this regard, clasps such as Adams, Schwarz, Arrowhead, Duyzing, Jackson, Crozat, ball, triangular, c and so on, have been developed. Furthermore, as much importance must be given to the level of comfort provided by the clasp as is given to its retentive property, particularly in appliances where long-term wear is essential. With regard to these two properties, proximal clasps render the greatest contribution through their high retentive capacity and ease of placement in the mouth. Hence, in spite of being developed originally for dentures, these clasps may be accommodated effectively in orthodontic appliances. In this paper, experiences acquired through practical application of proximal clasps are presented. PMID- 2230958 TI - New attachment formation following periodontal surgery in a dog. AB - We evaluated new attachment following treatment of experimental periodontitis in a canine model. Periodontal destruction was induced over an 8-month period using silk ligatures and a soft diet, and this remained stable for 170 days before surgery. After surgical scaling and root planing of eight bicuspid teeth, the apical end of the pockets was estimated using an occlusal stent and a periodontal probe, then marked with a blade. The root surfaces of three bicuspids were treated with citric acid for 3 min, and tetracycline salt was applied to the root surfaces of two teeth. The remaining three bicuspids served as controls. Postoperatively, no attempts were made to improve oral hygiene, and on day 48 light microscopic examination of biopsy materials revealed new attachment in all treated teeth. However, in some sections new cementum and new collagen formation was much more extensive and complete in both groups of experimental teeth than in the control teeth. PMID- 2230960 TI - Dental abrasion pattern in a selected group of Malaysians. AB - Among 350 inhabitants of two villages, 31 (8.9%) cleaned their teeth using table salt and charcoal applied to their forefinger or a Melastoma brush. As a result, all had distinct forms of abrasion cavity on the labial surfaces of their teeth. All of the above three agents are highly abrasive and injurious to both the hard and soft oral tissues. This dying practice is only popular among a very small number of persons in the older age group, and should be discouraged. PMID- 2230961 TI - Protein breakdown in submandibular glands rendered hypertrophic by amputation of lower incisor teeth in rats. AB - Protein breakdown in submandibular glands rendered hypertrophic by amputation of the lower incisor teeth in rats was investigated. Reduced protein breakdown was observed in the hypertrophic gland tissues, and was found to be inhibited by 20 mM epsilon-amino-n-caproic acid, an inhibitor of serine protease, and 50 microM leupeptin, an inhibitor of trypsin, plasmin, papain and cathepsin B, but not by 2 mM PMSF (phenylmethylsulfonyl fluoride), an inhibitor of serine protease, 10 microM pepstatin, an inhibitor of cathepsin D and 20 microM antipain, an inhibitor of cathepsin A and B. These results suggest that some serine proteases and leupeptin-sensitive proteases (presumably cathepsin B) participate in protein breakdown in hypertrophic gland tissues, and that hypertrophy of the submandibular glands is closely related to the reduced protein breakdown in these tissues. PMID- 2230962 TI - Squamous odontogenic tumor. AB - The twenty-fifth reported case of squamous odontogenic tumor is presented. The patient was a 39-year-old Chinese Malaysian male. The lesion was asymptomatic and did not recur after excision. It is important to distinguish this type of lesion from squamous odontogenic tumor-like proliferation. The rest of Malassez is thought to be responsible for the histogenesis of the lesion. Better understanding will only be achieved when more cases are reported and studied. PMID- 2230963 TI - An electron microscopic study of ectomesenchymal contacts in rat incisors. AB - In order to clarify connections between epithelium and mesenchymal tissue in the early stage of odontogenesis, the formation of ectomesenchymal contacts and the presence of coarse-textured material at the interface between ameloblasts (AMs) and odontoblasts (ODs) on growing rat incisors were studied by electron microscopy. The presecretory zone was classified into five regions according to the ultrastructure of each preameloblast (PA). The region where collagen fibrils could be observed was designated PZ-2, the region where predentin existed PZ-3, the region where the basal lamina began to disappear PZ-4, and the region where the basal lamina had disappeared PZ-5. In PZ-2, the cytoplasmic processes of PAs penetrated the basal lamina and reached the dental papilla cells. In some locations, ectomesenchymal contacts were also observed, in which the cytoplasmic processes of the PAs were in contact with those of the preodontoblasts (POs). In PZ-3, the distal cytoplasm contained large amounts of type-1 vesicles, and secretory granules. In the distal membrane of the PA, membrane invaginations containing fibrillar structures were visible. Also in some areas, the cytoplasmic processes at the distal ends of the PAs invaded the predentin. In the predentin, a large amount of coarse-textured material, considered to be the precursor of the enamel matrix, was observed. In PZ-3, a large number of cytoplasmic processes extended into the predentin, while in PZ-4, microvillus-like processes extended from the distal ends of the PAs, showing a high frequency of ectomesenchymal contact. It was suggested that secretory activity of the PAs was induced after ectomesenchymal contact had been accomplished, but that the PAs did not undergo morphological change into secretory ameloblasts. PMID- 2230964 TI - A clinicopathological study of so-called denture fibroma. AB - We investigated 60 cases of so-called denture fibroma, most of which occurred in women in their 50s to 70s. The most commonly affected areas were the upper alveolar ridge and the bottom of the alveolabial sulcus, and most of the prostheses responsible were complete dentures. Elevated and tumor-like lesions were most frequent. Histopathologically, about 60% of the lesions were of the fibromatous type. Degeneration and inflammation of the salivary glands were identified in one third of cases. PMID- 2230965 TI - Role of the United States in a changing world. The 1990 Harvey Cushing oration. AB - In discussing the role of the United States in world politics, President Jimmy Carter described the changes in Europe as it prepares for unification into one economic bloc; the deteriorating conditions in the third world; the impact of the recent changes in communist countries; and the persistence of regional wars and civil disputes. He summarized the policies and activities of The Carter Center in Atlanta, Georgia. This nonprofit organization receives no government funds and can act as an independent agent in areas such as disease eradication and promotion of food production in the third world countries, and can intercede on behalf of peace in countries with civil unrest. He urged the members of the Association, as leaders of society, to use their influence in alleviating worldwide suffering. PMID- 2230967 TI - Clinoidal meningiomas. AB - Anterior clinoidal meningiomas are frequently grouped with suprasellar or sphenoid ridge meningiomas, masking their notorious association with a high mortality and morbidity rate, failure of total removal, and recurrence. To avoid injury to encased cerebral vessels, most surgeons are content with subtotal removal. Without total removal, however, recurrence is expected. Recent advances in cranial-base exposure and cavernous sinus surgery have facilitated radical total removal. The author reports 24 cases operated on with vigorous attempts at total removal of the tumor with involved dura and bone. This experience has distinguished three groups (I, II, and III) which influence surgical difficulties, the success of total removal, and outcome. These subgroups relate to the presence of interfacing arachnoid membranes between the tumor and cerebral vessels. The presence or absence of arachnoid membranes depends on the origin of the tumor and its relation to the naked segment of carotid artery lying outside the carotid cistern. Total removal was impossible in the three patients in Group I, with postoperative death occurring in one patient and hemiplegia in another. Total removal was achieved in 18 of the 19 patients in Group II, with one death from pulmonary embolism. In the two patients in Group III, total removal without complications was easily achieved. PMID- 2230966 TI - Magnetic resonance imaging contrast agents: theory and application to the central nervous system. AB - The theoretical aspects of magnetic resonance (MR) imaging contrast agents are reviewed, and their current applications to the central nervous system (CNS) and their future applications are discussed. Profound differences exist between contrast agents used for MR imaging and computerized tomography (CT). In MR imaging, the contrast agents are not imaged directly but rather act on adjacent protons to shorten T1 and T2 relaxation times. This in turn results in signal intensity changes. The lanthanide metal, gadolinium, in the form of gadopentetate dimeglumine, has been found to be both safe and efficacious as the only currently approved contrast agent for MR imaging. Magnetic resonance imaging revolutionized the detection and treatment of disease affecting the brain and spine. Initially, it was thought that signal characteristics on MR imaging would allow differentiation of specific pathology. It was soon found that MR studies were able to detect more abnormalities but were less able to characterize them. The recent development of contrast agents for MR imaging has allowed this modality to surpass CT for the evaluation of most CNS lesions. At present, contrast-enhanced MR imaging is generally accepted as the study of choice for evaluating acoustic neurinomas, pituitary lesions, meningeal disease, primary and secondary brain tumors, active multiple sclerosis, intradural spinal neoplasms, intramedullary spinal disease, and postoperative states in both the spine and brain. Even when contrast-enhanced CT can detect the same abnormalities, evaluation of the lesions in multiple planes on MR imaging can sometimes yield invaluable information, especially prior to surgery. Future developments of contrast material for MR imaging include non-gadolinium compounds, intrathecal contrast media, cerebral blood flow and volume evaluation, and, possibly, antibody-labeled contrast agents. PMID- 2230968 TI - Cruciate paralysis: a clinical and radiographic analysis of injuries to the cervicomedullary junction. AB - Fourteen patients with superior cervical spinal cord injuries and the clinical signs and symptoms of cruciate paralysis are presented. This rare injury pattern is characterized by weakness of the upper extremities with little or no compromise of lower-extremity function following trauma to the superior spinal cord. Anatomically, cruciate paralysis is thought to represent selective injury to descending corticospinal tracts as they decussate at the cervicomedullary junction. The clinical and radiographic findings of each patient are outlined and the incidence and natural history of the injury syndrome, including a review of the literature, are presented. PMID- 2230969 TI - Unruptured intracranial aneurysms and arteriovenous malformations: frequency of intracranial hemorrhage and relationship of lesions. AB - Among 91 patients with unruptured intracranial arteriovenous malformations (AVM's), 16 patients had 26 unruptured intracranial saccular aneurysms. An actuarial analysis showed the risk of intracranial hemorrhage among patients with coexisting aneurysm and AVM to be 7% per year at 5 years following diagnosis compared to 1.7% for patients with AVM alone. The difference in length of survival free of hemorrhage was significant (log-rank, p less than 0.0007). Several angiographic and clinical parameters were investigated to better understand the relationship of these lesions. The aneurysms occurred in similar percentages in patients with small, medium, and large AVM's. Twenty-five aneurysms were on arteries feeding the malformation system, almost equally distributed proximally and distally. Eleven aneurysms were atypical in location, and all arose from primary or secondary branch feeders to the malformation; 24 were on enlarged feeding arteries. Eleven (16%) of the 67 patients with high-flow AVM's had associated aneurysms, compared with five (21%) of the 24 patients with low-flow AVM's. Four (16%) of 25 low-shunt malformations and 12 (18%) of 65 high shunt malformations had associated aneurysms. All five aneurysms associated with low-shunt malformations were on a direct arterial feeder of the malformation. These data suggest that the intracranial AVM's predispose to aneurysm formation within AVM feeding systems and that the mechanism is not simply based upon the high blood flow or high arteriovenous shunt in these systems. PMID- 2230970 TI - Systems analysis of cerebrovascular pressure transmission: an observational study in head-injured patients. AB - In an observational study in head-injured patients, cerebrovascular pressure transmission was investigated using a systems analysis approach whereby the blood pressure (BP) waveform was used as a measure of an input stimulus to the cerebrovascular bed (CVB) and the intracranial pressure (ICP) waveform as the response to that stimulus. The transfer function is a measure of how much pressure is transmitted through the CVB at a given frequency and is calculated using Fourier analysis of the pressure waveforms. The transfer function allows quantification of the pressure transmission performance of the CVB, thus providing a basis for comparison between normal and abnormal function. Fifteen hundred samples of ICP and BP waveforms were collected from 30 head-injured patients via microcomputer. Off-line spectral analysis of the waveform database revealed four main classes of transfer function: those with an overall flat transfer function (curve type 1); those with an elevated low-frequency response (curve type 2); those with an elevated high-frequency response (curve type 3); and those exhibiting both an elevated low- and high-frequency response (curve type 4). Curve types 2 and 4 were most often associated with raised ICP (greater than 20 mm Hg), whereas curve types 1 and 3 were most often affiliated with ICP less than 15 mm Hg. Studies of this type may provide insight into the pathophysiology of the CVB and ultimately aid in the prediction and treatment of raised ICP. PMID- 2230971 TI - Motility factor produced by malignant glioma cells: role in tumor invasion. AB - To better understand the cellular mechanism of tumor invasion, the production of a cell motility-stimulating factor by malignant glioma cells was studied in vitro. Serum-free conditioned media from cultures of rat C6 and human T98G cell lines contained a factor that stimulated the locomotion of the producer cells. This factor was termed the "glioma-derived motility factor." The glioma-derived motility factor is a heat-labile protein with a molecular weight greater than 10 kD and has relative stability to acid. The factor showed not only chemotactic activity but also chemokinetic (stimulated random locomotion) activity in the two types of glioma cells studied. Although glioma-derived motility factors in conditioned media obtained from two different cell origins are likely to be the same, chemokinetic migration of T98G cells to their conditioned medium was much stronger than that of C6 cells to theirs. Coincubation of cells with cytochalasin B, which disrupts the assembly of cellular actin microfilaments, almost completely inhibited the cell migration stimulated by glioma-derived motility factor. Cytochalasin B also induced marked alterations in cell morphology, including cell retraction and arborization, while the drug did not affect cell attachment to culture dishes. These results indicate that glioma cells produce a motility factor which may play a role particularly when tumor cells are detached and migrate away from the original tumor mass, thus promoting tumor invasion. Also, glioma cell migration stimulated by the motility factor requires the normal organization of cytoskeletons such as actin microfilaments. PMID- 2230972 TI - Antigen related to cell proliferation in malignant gliomas recognized by a human monoclonal antibody. AB - A human monoclonal antibody (CLN-IgG) was produced from a human-human hybridoma derived from lymphocytes of a patient with cervical carcinoma. The reactivities of this antibody with various human glioma tissues and cultured glioma cells and the characterization of the antigen recognized by CLN-IgG on malignant glioma cells were analyzed and reported. CLN-IgG reacted with various human glioma cells and glioma tissues, especially glioblastoma, but did not react with normal brain tissues or fetal brain tissues. A large amount of antigen recognized by CLN-IgG was expressed on cell membranes of undifferentiated glioma cells and of glioma cells at the G2/M tumor growth phase in cycling cells. Antigen recognized by CLN IgG was detected in only one of seven samples of cyst fluid, and was not detected in 27 serum samples or 18 samples of cerebrospinal fluid from glioma patients. CLN-IgG exhibited antibody-dependent cell cytotoxicity against U-25 1 MG glioma cells and primary cultured cells of glioblastomas and anaplastic astrocytomas. These data suggest that the antigen recognized by CLN-IgG might be related to cell proliferation in malignant gliomas. Thus, CLN-IgG might be useful for immunotherapy or immunoimaging of malignant gliomas. PMID- 2230973 TI - Cerebrovascular and metabolic effects on the rat brain of focal Nd:YAG laser irradiation. AB - To investigate the effects of focal neodymium:yttrium-aluminum-garnet (Nd:YAG) laser irradiation (lambda = 1060 nm) on regional cerebral blood flow, cerebral protein synthesis, and blood-brain barrier permeability, the parietal brain surface of 44 rats was irradiated with a focused laser beam at a constant output energy of 30 J. Survival times ranged from 5 minutes to 48 hours. Laser irradiation immediately caused well-defined cortical coagulation necrosis. Within 5 minutes after unilateral irradiation, 14C-iodoantipyrine autoradiographs demonstrated severely reduced blood flow to the irradiation site and perilesional neocortex, but a distinct reactive hyperemia in all other areas of the forebrain. Apart from a persistent ischemic focus in the vicinity of the cortical coagulation necrosis, blood flow alterations in remote areas of the brain subsided within 3 hours after irradiation. Autoradiographic assessment of 3H tyrosine incorporation into brain proteins revealed rapid onset and prolonged duration of protein synthesis inhibition in perifocal morphologically intact cortical and subcortical structures. Impairment of amino acid incorporation proved to be completely reversible within 48 hours. Immunoautoradiographic visualization of extravasated plasma proteins using 3H-labeled rabbit anti-rat immunoglobulins-showed that, up to 1 hour after irradiation, immunoreactive proteins were confined to the neocortex at the irradiation site. At 4 hours, vasogenic edema was present in the vicinity of the irradiation site and the subcortical white matter, and, at later stages (16 to 36 hours), also extended into the contralateral hemisphere. Although this was followed by a gradual decrease in labeling intensity, resolution of edema was still not complete after 48 hours. Analysis of sequential functional changes in conjunction with morphological alterations indicates that the evolution of morphological damage after laser irradiation does not correlate with the time course and spatial distribution of protein synthesis inhibition or vasogenic edema. Although the central coagulation necrosis represents a direct effect of radiation, the final size of the laser-induced lesion is determined by a delayed colliquation necrosis due to persistent perifocal ischemia. Extent and severity of ischemia in a zone with initial preservation of neuroglial cells can be explained by the optical properties of the Nd:YAG laser; extensive scattering of light within brain parenchyma associated with a high blood-to-brain absorption ratio selectively affects blood vessels outside the irradiation focus. PMID- 2230974 TI - Long-term evaluation of hemiparkinsonian monkeys after adrenal autografting or cavitation alone. AB - Autografts of adrenal medulla were implanted into preformed cavities in the caudate nuclei of four rhesus monkeys with hemiparkinsonism induced by 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP). Five other hemiparkinsonian monkeys underwent caudate cavitation, but received no tissue implant. All of the animals had marked bradykinesia of the affected arm and stable apomorphine-induced turning before cavitation or implantation. Moderate behavioral recovery was seen in all five monkeys with cavitation and two of the three monkey with long-term adrenal autografts (the fourth adrenal recipient was sacrificed 10 days after grafting). The improvement occurred months after the procedure and was not as early or as complete as that seen after fetal dopaminergic grafts. Surviving adrenal tissue was found only in the animal that showed no behavioral recovery. The other two adrenal autograft recipients (with no surviving adrenal medulla) and all of the animals with cavitation had ingrowth of dopaminergic fibers from the area olfactoria and nucleus accumbens into the caudate, oriented toward the cavity. These findings show that the mechanism of improvement after adrenal medullary implants for parkinsonism is not dopamine secretion by chromaffin cells, but may be related to the sprouted host fibers. The results also indicate that the limited recovery after adrenal implants in parkinsonian patients may be a result of the cavitation, and not necessarily the result of tissue implantation. PMID- 2230975 TI - Cerebral venous oxygen content as a measure of brain energy metabolism with increased intracranial pressure and hyperventilation. AB - In order to test the hypothesis that the cerebral arteriovenous oxygen difference (AVDO2) and venous oxygen content (VO2) could be used to monitor brain energy metabolism in the setting of increased intracranial pressure (ICP). 12 cats were studied with 31P-magnetic resonance spectroscopy. six cats were subjected to intracranial hypertension by cisternal infusion of saline. Energy failure occurred at an average AVDO2 of 8.4 +/- 3.2 vol% (+/- standard deviation) (range 4.7 to 14.7 vol%). The VO2 at the point of metabolic failure averaged 1.45 +/- 0.6 vol% and extended over a narrower range (1.0 to 2.9 vol%). In an additional six cats, ICP was raised to the threshold of metabolic failure and hyperventilation was then instituted (pCO2 10 to 18 torr). Five of the six cats experienced a drop in VO2 with hyperventilation. In two of these animals, hyperventilation resulted in a VO2 of 1.1 vol% or less and in metabolic failure as evidenced by a fall in phosphocreatine. It is concluded that a VO2 of less than 2 vol% is correlated with brain ischemia and that the safety of hyperventilation in the setting of increased ICP can be monitored by the use of VO2. PMID- 2230976 TI - Evidence of a local immune activation in cystic brain tumors. AB - The fluid of cystic brain tumors was characterized with regard to the protein content. In most malignant tumors, the concentrations of immunoglobulins G and M (IgG and IgM) were higher relative to other proteins in the cyst fluid than in the serum of the same patient. A markedly elevated ratio of monomeric to pentameric IgM was detected in the cyst fluid of two patients with glioblastomas. The results indicate a local immunoglobulin synthesis in malignant cystic brain tumors. It is hypothesized that higher-than-expected concentrations of IgG and IgM in cyst fluid as compared to plasma are a sign of an ongoing immune response triggered by the tumor. PMID- 2230977 TI - Biologically inert synthetic dural substitutes. Appraisal of a medical-grade aliphatic polyurethane and a polysiloxane-carbonate block copolymer. AB - Two types of artificial membranes, a medical-grade aliphatic polyurethane and a polysiloxane-carbonate block copolymer, were tested as substitutes for dura in 24 and 12 rabbits, respectively. The films were placed either epidurally, subdurally, or as dural grafts in equal subgroups of animals. The postoperative course was uneventful with no manifestations of convulsive disorder or cerebrospinal fluid leak. The animals were sacrificed 3, 6, or 9 months after implantation of the artificial membranes. Both types of artificial membranes were easily removed from the underlying nervous and the other surrounding tissues. The histological examination failed to reveal adhesions, neomembrane formations, or any type of foreign body reactions to the polyurethane film. The implantation of the polysiloxane-carbonate film caused no reaction when it was applied epidurally. As a dural graft, the polysiloxane-carbonate copolymer induced the formation of a thin neomembrane of one to two layers of fibroblasts which formed a watertight seal of the dural defect. A similar thin neomembrane was found to encase this artificial membrane in the group of animals in which it was implanted subdurally. There was no foreign body reaction to the polysiloxane-carbonate film. The authors conclude that these materials hold promise as dural substitutes or in the prevention of spinal dural scarring, and should be evaluated clinically. PMID- 2230978 TI - Epithelial cyst of the fourth ventricle. Case report. AB - A case of epithelial cyst in the fourth ventricle of a 4-year-old child is described. A single epithelial layer with a clear basement membrane lining the cyst wall was observed. There were no prominent histological findings to suggest a pathogenesis for this cyst based on immunohistochemical or ultrastructural studies; however, the cyst fluid contained significant amounts of carcinoembryonic antigen. It is considered that the epithelial layer lining the cyst wall was possibly of endodermal origin. PMID- 2230979 TI - Recurrence of acoustic neurilemoma as a malignant spindle-cell neoplasm. Case report. AB - A 75-year-old man presented with a right cerebellopontine angle tumor 11 months after complete macroscopic resection of a right acoustic neurilemoma. Histological examination of the recurrent tumor showed a malignant spindle-cell neoplasm with positive staining for S-100 protein. The patient had no stigmata of von Recklinghausen's disease. It is proposed that this recurrence represents progression from a benign to a malignant acoustic nerve-sheath tumor, an event that is extremely rare outside the clinicopathological context of neurofibromatosis. PMID- 2230980 TI - Toxoplasmosis of the conus medullaris in a patient with hemophilia A-associated AIDS. Case report. AB - Toxoplasma gondii has been reported to be the most common cause of focal brain lesions in patients with acquired immunodeficiency syndrome (AIDS). A case of intramedullary toxoplasmosis of the conus medullaris is reported in a patient with hemophilia A-associated AIDS. The diagnosis is discussed, with particular emphasis on the magnetic resonance imaging appearance. PMID- 2230981 TI - Spontaneous regression of giant arteriovenous fistulae during the perinatal period. Case report. AB - A unique case of spontaneous regression of giant arteriovenous fistulae during infancy is described in this report. A female infant, the product of normal labor and delivery, demonstrated severe ventriculomegaly and an intracranial hemorrhage at birth. Cerebral angiography at 5 days of age revealed several large fistulae fed by the anterior and middle cerebral arteries draining into the deep venous system through a dilated internal cerebral vein and ectatic vein of Galen. Two days following the angiogram, a second intracranial hemorrhage occurred. Active hydrocephalus developed over the next 6 months and was treated with ventriculoperitoneal shunting. When the child was 8 months of age, angiography failed to demonstrate the fistulae. It was postulated that pressure effects from the intracranial hematoma and long-standing intracranial hypertension as well as stenosis in the anomalous venous outflow resulted in vascular stasis, venous thrombosis, and selective arterial occlusion. Hydrocephalus was a result of the compression of the intraventricular foramina by dilated embryonic vessels. This anomaly, predominantly involving the anterior circulation, may be homologous to the vein of Galen aneurysm in the posterior circulation. PMID- 2230982 TI - Angiographic demonstration of acute phase of intracranial arterial spasm following aneurysm rupture. Case report. AB - A case documenting the acute phase of intracranial arterial spasm following rupture of an aneurysm arising from the left internal carotid artery is reported. The patient deteriorated due to recurrent hemorrhage while undergoing angiography 12 hours after the initial aneurysm rupture. The acute deterioration was accompanied by dilatation of the ipsilateral pupil and occurred during injection of contrast material. There was delayed filling of the middle cerebral artery complex along with this narrowing. The arterial narrowing was confirmed to have completely disappeared on an angiographic series performed 14 minutes after the first series of films. The etiology of the acute vasospasm is discussed. PMID- 2230983 TI - Subarachnoid hemorrhage caused by a fungal aneurysm of the vertebral artery as a complication of intracranial aneurysm clipping. Case report. AB - Intracranial aneurysms are an uncommon manifestation of fungal infection. A case is described in which the formation of an aneurysm followed an intracranial intraoperative Aspergillus infection attributable to a long period of preoperative antibiotic medication and immunosuppressive therapy with steroids. PMID- 2230984 TI - Propionibacterium encephalitis. PMID- 2230985 TI - Interposition vein grafts: cervical-to-petrous ICA bypass. PMID- 2230986 TI - Cancer clusters: latest studies do not support link between cancer mortality and radiation discharges. PMID- 2230987 TI - Nonuniformity in myocardial accumulation of fluorine-18-fluorodeoxyglucose in normal fasted humans. AB - In initial studies using fluorine-18-fluorodeoxyglucose (FDG) in normal fasted subjects, we observed disparities in the regional myocardial accumulation of this tracer. Accordingly, we systematically evaluated regional myocardial FDG accumulation in comparison with regional myocardial perfusion assessed with oxygen-15-water and oxidative metabolism assessed with carbon-11-acetate in nine normal subjects (four studied after a 5-hr fast and five studied both fasted and following glucose loading). Under fasting conditions, myocardial accumulation of FDG in the septum and anterior wall averaged 80% of that in the lateral and posterior walls (p less than 0.03). In contrast, after glucose loading the regional distribution of myocardial FDG accumulation became more homogeneous. Regional myocardial perfusion, oxidative metabolism, and accumulation of carbon 11-acetate were homogeneous under both conditions. Thus, under fasting conditions there are regional variations in myocardial accumulation of FDG, which are visually apparent, are not associated with concomitant changes in oxidative metabolism or perfusion, and cannot be attributed to partial-volume effects. This significant heterogeneity may limit the specificity of PET with FDG for detecting myocardial ischemia in fasting subjects. PMID- 2230988 TI - Regional heterogeneity of cardiac substrate metabolism? PMID- 2230989 TI - Quantification of the reversibility of stress-induced thallium-201 myocardial perfusion defects: a multicenter trial using bull's-eye polar maps and standard normal limits. AB - A multicenter trial was performed on 140 patients from four centers to determine the accuracy of quantitative analysis of stress/delayed thallium-201 myocardial tomograms using normal limits to assess the relative amount of reversibility of stress-induced defects. The patients were found to have 85 fixed and 124 reversible defects, as determined by visual interpretation. Reversibility bull's eye polar maps were compared to gender-matched normal limits from 36 normals. Regions were identified as reversible if their normalized difference between stress and 4 hr greater than 1.5 s.d.s. from the mean normal limits. Overall agreement between experts at multicenter sites and reversibility maps was 73% for reversible defects and 80% of fixed defects. Sensitivity in detecting reversibility was highest for the left circumflex (88%) and lowest for the right coronary (60%). These results indicate that reversibility polar maps and normal limits offer an objective, accurate technique for determining the reversibility of stress-induced perfusion defects. PMID- 2230990 TI - Limited precision of lumbar spine dual-photon absorptiometry by variations in the soft-tissue background. AB - The estimation error due to variations in soft-tissue baseline in lumbar bone mineral content (BMC) measured by dual-photon absorptiometry (DPA) was calculated with a new method of automatic baseline subtraction. In water phantom measurements, the s.d. of the soft-tissue (ST) baseline matched closely (r = 0.98) to the random error, calculated using 44 keV and 100 keV count rates and the directly determined baseline variations. In 21 volunteers and in 70 patients with osteoporosis, the ST variations were larger than the expected random error, revealing a source of error related to the inhomogeneity of soft tissue. The estimation error in BMC caused by ST variations was 0.7% in healthy subjects (mean BMC 40.5 gHA) and 1.5% in patients (mean BMC = 26.4 gHA). These results indicate that ST-related errors are an important limit to the precision of lumbar DPA measurements. PMID- 2230991 TI - Dual-photon absorptiometry in clinical practice. PMID- 2230992 TI - Imaging of tumor in patients with indium-111-labeled biotin and streptavidin conjugated antibodies: preliminary communication. AB - Tumor localization in patients has been achieved through the in vivo use of streptavidin and biotin. In these preliminary studies, the monoclonal antibody HMFG1 was conjugated with streptavidin and 1 mg was administered intravenously to each of 10 patients with documented squamous cell carcinoma of the lung. Two to 3 days later, 111In-labeled biotin was also administered intravenously. No evidence of toxicity was observed. Background radioactivity levels were reduced in liver (1% ID at 24 hr) and kidneys (2%) and in all other normal tissues and blood. Images of lung tumor were obtained in as little as 2 hr following administration of labeled biotin. In eight patients, tumor was detected with labeled biotin alone without the previous administration of streptavidin-conjugated antibody but in three of these patients, the images were improved with the prior administration of conjugated antibody. These results suggest that this approach may improve the tumor-to-normal tissue radioactivity ratios in radioimmunotargeting. PMID- 2230993 TI - Immunoscintigraphy of ovarian cancer with indium-111-labeled OV-TL 3 F(ab')2 monoclonal antibody. AB - The safety and diagnostic accuracy of immunoscintigraphy with the indium-111 labeled monoclonal antibody OV-TL 3 F(ab')2(111In-OV-TL 3 F(ab')2) for diagnosis and follow-up of ovarian cancer was prospectively studied in 31 patients. Planar and SPECT scintigraphy were performed up to 4 days after i.v. injection of 140 MBq 111In-OV-TL 3 F(ab')2. Surgical evaluation was possible in 22 out of 31 patients. Imaging results were compared with X-ray computed tomography, ultrasound, and CA 125 serum level using the histologically confirmed surgical findings as a "gold standard." Apart from a transient rash observed in two patients, no other immediate or delayed adverse reactions were observed. Within the surgically evaluated group, ovarian cancer lesions were detected in 16 out of 17 patients (94%). Of 45 distinct tumor deposits found at operation, 67% were detected and localized with immunoscintigraphy while X-ray computed tomography and ultrasound visualized 53% and 23%, respectively. PMID- 2230994 TI - Myocardial accumulation of iodinated beta-methyl-branched fatty acid analogue, iodine-125-15-(p-iodophenyl)-3-(R,S)methylpentadecanoic acid (BMIPP), in relation to ATP concentration. AB - To clarify the relationship between the myocardial accumulation of 125I-15-(p iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and intracellular adenosine 5'-triphosphate (ATP) content, the effect of 2,4-dinitrophenol (DNP, an electron transport uncoupler) on myocardial BMIPP accumulation was studied, in comparison with that of thallium-201-chloride (201Tl-Cl). In the mouse myocardium, DNP decreased the intracellular ATP and ADP levels, without affecting either acyl-CoA synthetase activity or the level of CoA-SH. Following treatment with DNP, decreases in myocardial BMIPP accumulation correlated well with those of ATP, while 201Tl-Cl showed slightly increased accumulation in the myocardium. Thus, in some diseases, BMIPP may be useful in evaluating myocardial ATP levels. PMID- 2230996 TI - The potential of 2-deoxy-2[18F]fluoro-D-glucose (FDG) for the detection of tumor involvement in lymph nodes. AB - To assess the potential of FDG for PET imaging of nodal tumor metastases, we evaluated its uptake into normal lymph nodes, tumor-involved lymph nodes, and subcutaneous tumor xenografts in rodents. Normal lymph nodes in mice and rats accumulate FDG moderately, developing node/blood ratios of 1.3-11.9/1 at 2 hr following i.v. injection. By contrast, FDG given subcutaneously to healthy Sprague Dawley rats developed very high normal draining lymph node/blood ratios (272/1) versus 7.7/1 by i.v. injection. In nude mice, subcutaneous human ovarian cancer xenografts had 1.27-fold more uptake relative to blood than did normal popliteal lymph nodes. Subcutaneous tumor xenografts of rat breast cancer developed tumor/normal node uptake ratios of 4.91 +/- 0.43/1 and tumor/blood ratios of 6.6 +/- 0.9 at 2 hr postinjection. Mouse nodes involved with 38C13 murine B-cell lymphoma had mean node/blood ratios of 42.9 +/- 6.7/1 and tumored node/normal lymph node uptake of 6.3/1. Thus, FDG given intravenously but not subcutaneusly (due to high normal nodal uptake) has potential as an agent for the detection of metastatic tumors in regional lymph nodes using PET scanning. PMID- 2230997 TI - Axillary lymphoscintigraphy for breast cancer: should we do it? Can we do it? PMID- 2230995 TI - Metabolism of beta-methyl-heptadecanoic acid in the perfused rat heart and liver. AB - The metabolism of beta-methyl-[1-14C]heptadecanoic acid, a potential myocardial imaging agent, was investigated in perfused hearts and livers from rats. Hepatic uptake is approximately 4.5 times greater than cardiac uptake. In the heart, 66% of beta-methyl-heptadecanoic acid metabolism occurs via omega-oxidation, 33% by esterification and less than 1% via alpha-oxidation. In contrast, 53% of hepatic metabolism of beta-methyl-heptadecanoic acid occurs via alpha-oxidation, 27% via omega-oxidation, and 20% via esterification. Perfusion of hearts and livers with concentrations of beta-methyl-heptadecanoic acid 100 to 1000 times greater than that used for myocardial imaging does not alter any of the physiological and biochemical parameters measured. In the perfused liver, 3-methyl-[1-14C]glutarate was identified as the principal hydrosoluble catabolite of beta-methyl heptadecanoic acid. PMID- 2230998 TI - Complex partial epilepsy: the role of neuroimaging in localizing a seizure focus for surgical intervention. PMID- 2230999 TI - Diagnostic use of angiotensin converting enzyme (ACE)-inhibited renal scintigraphy in the identification of selective renal artery stenosis in the presence of multiple renal arteries: a case report. AB - In patients with renovascular hypertension, it is unknown whether the angiotensin converting enzyme-(ACE) inhibited renal scan will identify stenosis of a segmental branch of a single renal artery or of an accessory artery where multiple renal arteries are present. Since multiple renal arteries may be present in approximately 25% of all individuals, it will be important to establish whether the ACE-inhibited renal scan is useful in this population. We report a case of stenosis involving a renal artery in a patient with multiple renal arteries, successfully identified by ACE-inhibited renal scintigraphy. PMID- 2231000 TI - Myocardial uptake of indium-111-labeled antimyosin in acute subendocardial infarction: clinical, histochemical, and autoradiographic correlation of myocardial necrosis. AB - Indium-111-labeled antimyosin has been utilized in the diagnosis and localization of acute transmural myocardial infarction. The present report describes a patient who presented with a massive subendocardial infarction. Two days after the injection of antimyosin, the patient's clinical status markedly deteriorated and he expired. Postmortem examination demonstrated severe three-vessel coronary artery disease with extensive myocyte death in the endocardium. Autoradiography and histochemical staining of the prosected heart demonstrated high correlation for myocardial necrosis and corresponded to clinical evidence for diffuse subendocardial infarction. PMID- 2231001 TI - Radioimmunoscintigraphy using iodine-131-anti-CEA monoclonal antibodies and thallium-201 scintigraphy in medullary thyroid carcinoma: a case report. AB - This case report demonstrates the use of thallium-201 (201Tl) scans versus iodine 131- (131l) anti-CEA F(ab')2 scans in a patient with high serum CEA levels due to metastases of medullary thyroid carcinoma in the suprarenal region and sacroiliacal region. Scintigraphy using monoclonal antibodies directed against CEA showed a higher tumor uptake (0.26% dose and 0.64% dose, respectively) than a thallium scan and is believed to be promising for future radiotherapeutic applications. PMID- 2231002 TI - Reconstruction of Fourier coefficients: a fast method to get polar amplitude and phase images of gated SPECT. AB - Gated SPECT (GASPECT) during radionuclide ventriculography (RNV) is a time consuming procedure requiring extended hard- and software. Furthermore, the procedure suffers from poor count statistics. Our method tries to overcome these difficulties by exploiting the count summation effect of Fourier analysis. The sine and cosine coefficients of the first harmonic are extracted from the gated views and reconstructed. This, in fact, results in an improvement of the count statistics by a factor of four combined with a tremendous reduction of disc space requirements. Using short-axis slices, bull's-eye plots of the amplitude and phase of the left ventricle are calculated. Cardiac functions and localization and extent of any malfunction are documented three-dimensionally without superposition. PMID- 2231003 TI - "CORT-EX:" a program for quantitative analysis of brain SPECT data. AB - A program was developed to extract from brain SPECT data global as well as regional concentrations of a radiopharmaceutical while allowing for improved subjective evaluation of its distribution. This program was used to process the data obtained from 17 normal subjects, 20 min, 2 hr, and 4 hr after the injection of iodine-labeled iodoamphetamines. The mean absolute cortical uptake at these three time periods was 0.921 (+/- 0.185), 0.803 (+/- 0.107), and 0.748 (+/- 0.103) in arbitrary units (+/- s.d.), respectively. The regional distribution of the tracer became more uniform with time due to an uneven washout rate. The cerebellum was noted to have a very high variability in its uptake and a high washout rate, making it unsuitable as an internal standard for relative quantification. Finally, a repeat study was performed on 10 subjects. No significant difference could be demonstrated in the mean uptake of the group at 2 and 4 hr, however the difference observed in the 20 min uptake values was significant at the p = 0.05 level. PMID- 2231004 TI - Evaluation of techniques for the elimination of "hot" bladder artifacts in SPECT of the pelvis. AB - The purpose of this study was to validate the usefulness of two digital filtering techniques used to eliminate the artifacts caused by rapid bladder filling during SPECT of the pelvis. A dynamic phantom model was used containing two hips and a bladder. The phantom was studied under three conditions--bladder empty, filling, and full. The ability of the pixel truncation and interpolative background replacement techniques to eliminate bladder artifacts was assessed. Both techniques gave similar results and resulted in significant (but not complete) recovery of activity in the hips. Quantitative analysis of pixel counts over each hip shows that the measured activity was variable and approximately 20%-30% less than that seen in the empty bladder study. The use of left/right ratio to quantitate differences in hip activity was highly inaccurate despite the use of these filtering techniques. In summary, while these techniques significantly improve image quality, caution should be exercised, particularly in the evaluation of the medial aspects of the hips. PMID- 2231005 TI - Three-dimensional assessment of myocardial oxidative metabolism: a new approach for regional determination of PET-derived carbon-11-acetate kinetics. AB - We have developed a new analysis algorithm which generates polar coordinate maps of myocardial carbon-11-(11C) acetate kinetics. In 10 normal subjects (n = 20 studies), myocardial 11C clearance rate constants (k) averaged 0.057 +/- 0.009 (per minute). Regional k-values varied only 10.6 +/- 2.4% in the normal left ventricle. However, there was a small but significant segmental variation with increased 11C clearance in the septal, anterior, and basal regions (p less than 0.05). Since 11C clearance rates reflect tri-carboxylic acid cycle flux, these results suggest that myocardial oxidative metabolism is relatively homogeneous in the normal human heart at rest with minor regional variations, which possibly reflect varying regional wall stresses or substrate utilization. The proposed approach provides three-dimensional evaluation of regional oxidative metabolism which will permit characterization of the location, extent, and severity of myocardial disease. PMID- 2231006 TI - Treatment planning for internal radionuclide therapy: three-dimensional dosimetry for nonuniformly distributed radionuclides. AB - A calculational approach is described that provides the spatially varying radiation absorbed dose, presented as isodose contours superimposed on CT images, from nonuniform and/or irregular cumulated activity distributions. CT images are read from magnetic tape and are displayed on a high-resolution color graphics display monitor. Source tissue geometries are defined on a series of contiguous CT images automatically (by an edge detection algorithm) or manually (using a trackball), thereby obtaining a three-dimensional representation of the various source volumes of activity. Dose calculations are performed using a radionuclide specific absorbed dose point kernel in the form of a lookup table. The method described yields the spatially varying dose delivered to tumor and normal tissue volumes from a patient-specific cumulated activity distribution in a clinically implementable manner. This level of accuracy in determining normal tissue and tumor doses may prove valuable in the evaluation and implementation of radionuclides and radiolabeled compounds for therapeutic purposes. PMID- 2231008 TI - Defective parallel-hole collimator encountered in SPECT: a suggested approach to avoid potential problems. PMID- 2231007 TI - Preparation of technetium-99m-HMPAO. PMID- 2231009 TI - NRC issues interim rule on medical use of radionuclides. PMID- 2231010 TI - Ambulatory care. An objective assessment. AB - Budget constraints, loss of staff, and the inability of administrators to define nursing needs in the outpatient department lead to the development of a tool to define the role of the healthcare provider in the outpatient department. The author discusses the tool's use in categorizing and quantifying nursing activities. Administrators in ambulatory care now have an opportunity to use this readily adaptable method in their outpatient areas to assist in developing quality, cost-effective nursing. PMID- 2231011 TI - Nursing research utilization techniques. AB - The author reviews the literature to identify techniques for the facilitation of nursing research utilization. Nine general themes were employed to organize techniques. Techniques within each theme may be implemented by individual nurses, small groups, or organizations. The review supports the need for the concerted efforts of the entire profession to implement research findings into practice. PMID- 2231012 TI - Planning your replacement budget. PMID- 2231013 TI - Evaluation: myths, mystiques, and obsessions. AB - Nurse executives, administrators, and managers are constantly being challenged by the changes in healthcare. Although it sometimes seems there is really nothing new, proactive visionary nurse administrators can rediscover, redesign, and redirect their own and others' activities to achieve organizational effectiveness. Such approaches require periodic examination of all strategies and practices--past, present, and future--for their relevance, practicality, and success. The editors of "Executive Development" reflect on topics important to organizational life. PMID- 2231014 TI - Team nursing revisited. AB - The use of team nursing as a model of nursing care is being reconsidered by many nurse executives as a strategy to meet patient needs while efficiently using nursing resources. The author examines the historical development and original concepts of team nursing, discusses problems that led to the criticism of team nursing, and suggests ways in which team nursing can be enhanced for future use. PMID- 2231015 TI - The impact of the 23-hour patient on nursing workload. AB - Decreasing length of in-patient stay and increasing the number of outpatient procedures being performed has led to the creation of the 23/24-hour observation patient. In this study, the authors show that the addition of observation patients to aggregate workload data causes a meaningful staffing deficit 60-90% of the time in three out of four clinical areas studied. The authors explore the statistical impact on staffing of the addition of observation patients to aggregate inpatient data and provide several strategies for staffing. PMID- 2231016 TI - Marketing the home healthcare agency. Do nurses and physicians agree? AB - Increasingly, hospital nurse administrators are being called upon to organize and implement home care services and to market these services to physicians, patients, and family members. A survey of hospital personnel revealed that both nurses and physicians perceived themselves as the persons primarily responsible for determining the patient's need for postdischarge home care. In listing criteria for selecting a home care agency for patient referral, nurses and physicians rated service dependability and nursing care quality as the most important criteria. PMID- 2231017 TI - Failure to demonstrate an effect of dietary fatty acid composition on body weight, body composition and parameters of lipid metabolism in mature rats. AB - The objectives of the present study were to examine the effects of dietary fatty acid composition on body composition and on several parameters of lipid metabolism in adipose tissue and to assess the ease of weight loss with restricted dietary intake. Rats were fed diets containing 14% fish oil, safflower oil or beef fat plus 2% corn oil. These diets were fed ad libitum for 4 wk (first phase). A number of the animals from each group were killed, and the others were fed 50% of their first-phase food intake for an additional 4 wk (second phase). The diets used in the second phase contained 3% of the above fats plus 2% corn oil. Food consumption, food efficiency and body weights were monitored. After the rats were killed, fatty acid composition of epididymal fat pads was examined. In addition, in vivo lipolysis and in vitro lipogenesis in epididymal fat pads were examined. The results indicate that dietary fatty acid composition had no effect on body weight, food consumption, in vivo lipolysis and in vitro lipogenesis in epididymal fat pads. In addition, although dietary fatty acid manipulation resulted in alteration in adipose tissue fatty acid composition, it had no effect on the rate of weight loss, body composition, in vivo lipolysis and in vitro lipogenesis in epididymal fat pads. It is concluded that dietary fatty acid composition does not play a role in body composition and in lipid metabolism in adipose tissue of mature rats. PMID- 2231018 TI - Pectin isolated from prickly pear (Opuntia sp.) modifies low density lipoprotein metabolism in cholesterol-fed guinea pigs. AB - The effect of prickly pear soluble fiber on low density lipoprotein (LDL) metabolism was investigated by feeding male guinea pigs either a nonpurified diet containing 0.25% cholesterol (HC diet) or the HC diet + 1% prickly pear pectin (HC-P diet). Plasma cholesterol levels were significantly decreased by the HC-P diet, with a 33% decrease in LDL levels (p less than 0.02) and an increase in LDL density. Hepatic free and esterified cholesterol levels were reduced 40 and 85%, respectively (p less than 0.002), by the HC-P diet. Hepatic microsomal 3-hydroxy 3-methylglutaryl coenzyme A reductase levels were not different. 125I-LDL binding to hepatic membranes was increased 1.7-fold by the HC-P diet (p less than 0.001), with receptor affinity (Kd) being unaltered and receptor number (Bmax) being significantly increased (p less than 0.001). These data suggest that prickly pear pectin may act by a mechanism similar to that of bile acid-binding resins in lowering plasma cholesterol levels. The observed reduction in LDL and hepatic cholesterol levels and increase in LDL density and hepatic apolipoprotein B/E receptors are responses suggesting an increased demand on hepatic cholesterol from increased excretion of bile acids and interruption of the enterohepatic circulation. PMID- 2231019 TI - Less body fat accumulation in rats fed a safflower oil diet than in rats fed a beef tallow diet. AB - The effects on body fat accumulation of long-term feeding of high fat diets of differing fatty acid composition were studied in rats. The rats were meal-fed isoenergetic diets based on safflower oil or beef tallow for 4 mo. Each diet was freshly prepared every day throughout the experimental period. Oxygen consumption and carbon dioxide production for 6 h after meals were measured between the 50th and 54th d of the experimental period. Oxygen consumption for 3 h after meals was significantly greater in the safflower oil diet group than in the beef tallow diet group, indicating greater diet-induced thermogenesis in the former group. From the assessment of respiratory quotient, the fat oxidation rate was also higher in the former. After the experimental period (4 mo), body fat accumulation was significantly less in the rats fed safflower oil. This difference was, at least in part, ascribed to increased diet-induced thermogenesis and fat oxidation. Serum triacylglycerol level was markedly lower in the rats fed safflower oil than in those fed beef tallow. The lipoprotein lipase activities in heart and soleus muscle after meals appeared to be higher in the former than in the latter. These results suggest that the consumption of the safflower oil diet increased lipoprotein lipase activity in heart and skeletal muscle, resulting in the elevation of fat oxidation rate and the depression of serum triacylglycerol level. PMID- 2231020 TI - Plasma amino acids and cholesterol following consumption of dietary casein or soy protein in minipigs. AB - Numerous investigators have claimed that protein-induced differences in plasma cholesterol are mediated by differences in amino acid composition. We have explored whether the venous postprandial amino acid profile reflects differences in the amino acid composition of the protein consumed. Six adult Gottingen miniature pigs were fed a semisynthetic diet based on either casein or soy protein isolate. Frequent blood sampling was performed over a whole day after consumption of each diet for 6 wk. Postprandial plasma amino acid concentrations reached their maxima within the first 3 h. A group of eight protein amino acids (Met, Arg, Tyr, Val, Trp, Leu, Lys and Cys) exhibited the most marked and significant protein-dependent differences during this early postprandial phase, whereas Thr and His showed less marked differences. With one exception (Ser) all protein amino acids exhibited venous plasma concentration changes in qualitative accordance with their content in the dietary protein consumed. In quantitative terms, however, venous plasma amino acid changes were less marked than expected from the amino acid composition of the dietary proteins. We conclude that neither the considerable number of amino acids showing differences as reported herein nor the multitude of contradictory reported by others concerning single amino acids affecting serum cholesterol favor the hypothesis that one or several amino acid(s) cause protein-induced hypercholesterolemia. PMID- 2231021 TI - Comparison of effects of dietary glucose versus fructose during pregnancy on fetal growth and development in rats. AB - Dietary carbohydrate during pregnancy is essential. Whether this requirement is specific to glucose was investigated. We examined whether fructose at low, intermediate and high levels can substitute for an isoenergetic amount of glucose by feeding graded levels of both carbohydrates (0, 4, 12, 60%) in a triglyceride based diet throughout pregnancy. It was concluded that the carbohydrate requirement for the rat during pregnancy is not specific to glucose and that the level, not the type, of carbohydrate was critical (experiment 1). A second aspect of the study (experiment 2) was the comparison of isoenergetic, low carbohydrate diets containing different sources of 4% glucose equivalents: glucose, fructose or lipid-glycerol. Fructose and lipid-glycerol were not equivalent substitutes for glucose in the pregnant rat dam at these very low intakes. PMID- 2231022 TI - Relationship between blood, liver and brain pyridoxal phosphate and pyridoxamine phosphate concentrations in mice. AB - Plasma pyridoxal 5'-phosphate (PLP) concentrations are considered to be the most reliable single indicator of vitamin B-6 nutritional status and are thought to reflect tissue PLP and pyridoxamine 5'-phosphate (PMP) levels. We investigated the relationship between dietary level of pyridoxine hydrochloride (PN-HCl) and concentrations of PLP in blood and PLP and PMP in liver and brain of mice. Female heterogeneous stock mice, 60 to 90 d old, were fed purified diets containing 0.5, 1.0, 2.0, 3.0, 5.0, or 7.0 mg PN-HCl/kg diet for 5 wk. PLP and PMP concentrations were determined by a spectrophotometric apotryptophanase assay. PLP content of plasma, erythrocytes, whole blood, liver and brain and PMP levels in liver and brain were highly correlated with dietary level of PN-HCl (r values ranged from 0.81 to 0.94, n per correlation = 32 to 43). By using the entire range of dietary levels of PN-HCl, both plasma and erythrocyte PLP were found to be significantly correlated with tissue PLP and PMP concentrations. For any one dietary level, however, correlations between plasma or erythrocyte PLP and tissue PLP and PMP concentrations were low and nonsignificant. These results suggest that plasma PLP levels may be suitable to determine vitamin B-6 status of populations, but not to reliably predict tissue concentrations of PLP or PMP in individuals. PMID- 2231023 TI - Dependence of vitamin B-6 status assessment on alcohol intake among elderly men and women (Dutch Nutrition Surveillance System). AB - To obtain more insight into the effect of moderate alcohol intake on vitamin B-6 status indicators, we studied the associations of alcohol intake (unadjusted and adjusted for intake of vitamin B-6 and protein) with the erythrocyte aspartate aminotransferase activation coefficient (EAST-AC) and plasma pyridoxal 5' phosphate (PLP) level. Data obtained from men (n = 224) and women (n = 217) aged 65-79 (nationwide sample in the Netherlands) were used for this purpose. Although alcohol intake (a maximum of 21% of the energy came from alcohol) tended to be positively associated with PLP, this association never reached statistical significance (p greater than or equal to 0.05). EAST-AC was inversely associated with alcohol intake, whether or not it was adjusted for vitamin B-6 and protein intake. Similar results were found for the total EAST activity (after adding PLP) or apoenzyme activity; the basal EAST activity (before adding PLP) or holoenzyme activity was not associated with the alcohol intake. These results indicate that caution is needed in the interpretation of the specificity of EAST-AC (i.e., the degree to which EAST-AC is unaffected by other factors) as an indicator of vitamin B-6 intake. PMID- 2231024 TI - Relationship between vitamin B-6 status and elevated pyridoxal kinase levels induced by theophylline therapy in humans. AB - Theophylline administration to seven healthy male volunteers resulted in a rapid and significant decline in both plasma and erythrocyte pyridoxal-5'-phosphate levels. Total erythrocyte pyridoxal kinase levels increased during 15 wk of theophylline treatment from a mean initial activity of 19.23 +/- 5.03 (mean +/- SD) to 62.64 +/- 11.59 nmol pyridoxal-5'-phosphate formed/(g hemoglobin.h). Although plasma pyridoxal levels remained normal, the threefold increase in total erythrocyte pyridoxal kinase activity levels did not normalize plasma and erythrocyte pyridoxal-5'-phosphate levels. Pyridoxal-5'-phosphate hydrolysis was not affected by theophylline therapy. Increased pyridoxal oxidation was confirmed by elevated urinary 4-pyridoxic acid excretion after 15 wk of theophylline treatment. Mean erythrocyte alanine aminotransferase activity declined by 70%, and aspartate aminotransferase activity declined by 50%, indicating that decreased availability of pyridoxal-5'-phosphate can have widespread metabolic consequences. We conclude that the effect of theophylline on vitamin B-6 metabolism is not transitory and cannot be overcome by elevated intracellular levels of pyridoxal kinase. However, pyridoxine supplementation (10 mg/d for 1 wk) normalized indices of vitamin B-6 status and reversed the downward trend in both alanine aminotransferase and aspartate aminotransferase activity levels. PMID- 2231025 TI - Effects of dietary minerals on acid-base balance and eggshell quality in chickens. AB - Three experiments were conducted in hens to determine the effects of high levels of dietary phosphorus (P, 1-1.5%), chloride (Cl, 0.8%) or both on acid-base balance and eggshell quality and to consider whether any adverse effects on eggshell quality can be attributed to alteration of blood acid-base balance. Eggshell quality and values for a blood indicator of acid-base balance were reduced by high levels of dietary P or Cl in all of the experiments. Eggshell quality and values for the blood acid-base indicator were further reduced by high dietary levels of the combination of minerals. The adverse effects associated with high levels of the combination were greater than the sum of adverse effects associated with high levels of each mineral. The effects of P and Cl on plasma levels of these minerals were inconsistent and varied among experiments. The use of pair-fed controls revealed that the adverse effects of combined P and Cl on eggshell quality and acid-base balance were independent of their effects on feed and calcium intake. Calcium excretion was increased by consumption of the high P, high Cl diet. The information obtained from these experiments suggests that the adverse effects of high levels of dietary P and/or Cl on eggshell quality may be due, at least in part, to increased Ca excretion. This, in turn, may be mediated by acidemia resulting from the dietary manipulations, although the present data were insufficient to provide a direct link between acidemia and Ca excretion. PMID- 2231026 TI - Effects of cellular copper content on copper uptake and metallothionein and ceruloplasmin mRNA levels in mouse hepatocytes. AB - The intracellular copper content of mouse hepatocytes has been altered by incubating with either increasing amounts of extracellular copper or increasing amounts of diamsar, a copper chelator. Metallothionein 1 (MT1) and MT2 mRNA levels in the cells increased in proportion to the intracellular copper concentration. The degree of stimulation was similar for both MT1 and MT2, with mRNA levels increasing approximately fourfold for a six- to eightfold increase in intracellular copper levels. In contrast, neither copper uptake nor ceruloplasmin mRNA showed any response to intracellular copper levels. Unlike the situation in the rat, there was no clear evidence for saturation of copper uptake. Incubating cells with increasing amounts of 64Cu resulted in a linear increase in the amount taken up over 2 h. The amount of 64Cu accumulated was the same in control and copper-depleted cells, which suggests that neither ceruloplasmin production nor copper uptake is regulated by intracellular copper levels. However, other possibilities, such as the chelators not being able to deplete the pool(s) responsible for the control of ceruloplasmin production or copper uptake, must also be considered. PMID- 2231027 TI - Response of hormones modulating plasma cholesterol to dietary casein or soy protein in minipigs. AB - To elucidate the mechanism mediating the effect of dietary casein or soy protein on serum cholesterol concentrations we followed the endocrine response to the intake of these dietary proteins. The hormones analyzed were those known to modulate serum cholesterol concentration. A 7-wk crossover nutrition study was performed with six adult Gottingen minipigs consuming semisynthetic diets based on either 20 wt% casein or soy isolate. At d 42 and 49, concentrations of six hormones were determined in 22 blood samples taken over the whole day. There were no significant differences in insulin, glucagon, the insulin/glucagon ratio, hydrocortisone or triiodothyronine among dietary groups. In the late postprandial phase (5 h after the meal and later) there were significantly higher growth hormone concentrations in soy-fed animals. At all times of the day, total and free thyroxine concentrations were higher after soy feeding than after casein feeding. On average, total and free thyroxine concentrations were 34 and 26% higher with soy protein feeding than with casein feeding. Our data agree with other reports of protein-dependent changes of thyroid hormones and may explain why different dietary proteins have different effects on serum cholesterol levels in sensitive species. PMID- 2231028 TI - Effects of dietary restriction on age-related immune dysfunction in the senescence accelerated mouse (SAM). AB - The effects of age and dietary restriction on immune response were investigated using an animal model of accelerated senescence (senescence accelerated mouse, SAM). The experimental groups consisted of control (ad libitum fed) and restricted groups (fed 60% of energy intake of the controls). Spleen weight and total number of splenic cells were significantly lower in the food-restricted group at 8 mo of age. Percentages of T (Thy-1.1+) and B (surface Ig+) cells in the splenic cells were not significantly different between the two groups. The number of direct hemolytic plaque-forming cells per 10(6) spleen cells 4 d following immunization with sheep red blood cells and dinitrophenyl-Ficoll was significantly greater in the 8-mo-old mice in the food-restricted group than in the control group. In the latter group, antibody responses Progressively decreased with age. Mitogen responses to concanavalin A and lipopolysaccharide were maintained in the food-restricted group but were depressed in the control group at 8 mo. In addition, though autoantibody to single-stranded DNA increased in the control group with advancing age, there was a steady decrease in the food restricted group until 8 mo. Serum immunoglobulin (IgA and IgM) concentrations were significantly lower in the food-restricted group than in controls at 8 mo of age. Therefore, our results suggest that when senescence accelerated mice are subjected to food restriction, there may be a modulatory effect on the immune dysfunction associated with advancing age. PMID- 2231029 TI - Dietary energy restriction in mice reduces hepatic expression of glucose regulated protein 78 (BiP) and 94 mRNA. AB - The influence of life span-prolonging dietary energy restriction on hepatic expression of glucose-regulated protein 78 and 94 (GRP78 and GRP94) RNA was investigated in female C3B10RF1 mice. Mice were either fed ad libitum or fed diets reduced 20 or 40% in energy but containing approximately equivalent amounts of protein, fats, vitamins and minerals. Aging produced no changes in GRP mRNA. However, GRP78 and GRP94 mRNA levels were reduced approximately 50 and 40%, respectively, by 40% energy restriction. This level of energy restriction produced a 43% reduction in the mean plasma glucose levels of young and old mice. The changes in GRP mRNA expression appear to be specific, because the levels of these RNAs were normalized to the level of polyadenylated RNA, and no changes were detected in the levels of a number of other mRNAs. Although extreme glucose deprivation increases GRP mRNA levels in cultured cell lines, physiologically relevant reductions in blood glucose had the opposite effect in the liver, in vivo. The regulatory pathway responsible for these effects is not known. GRP mRNA levels are elevated by agents that increase the level of malfolded proteins in the endoplasmic reticulum. Thus, energy restriction may act to reduce malfolded proteins in the endoplasmic reticulum of hepatic cells. PMID- 2231030 TI - Macronutrient selection in rats: effect of fat type and level. AB - The effect of type and level of dietary fat on subsequent diet selection was examined in young Sprague-Dawley rats. Isoenergetic, isonitrogenous diets composed of corn oil or tallow (commercial grade), each at 5 or 34%, were fed to rats for 2 wk, and their preference for diets covarying in carbohydrate and protein was subsequently tested. When compared to either of the corn oil groups or the 5% tallow group, rats previously fed the high tallow diet selected more protein and less carbohydrate. Subsequent experiments testing the effects of 5, 20 or 34% tallow indicated that this preference for protein was induced by exposure to the tallow diets for only 18 h. In addition, the 34% tallow group selected more protein than did rats fed 5 or 20% tallow. Tests of diet selection with 5 or 34% corn oil, tallow or hydrogenated coconut oil indicated that rats fed 34% tallow ate significantly more protein than the 34% corn oil group. Furthermore, animals fed a 34% pure, additive-free tallow diet exhibited a preference for protein. These studies suggest that the type and level of dietary fat interact to influence dietary selection. PMID- 2231031 TI - Pteroylpolyglutamate concentration and glutamyl chain length in rat tissues. PMID- 2231032 TI - Impact of the availability of a prior electrocardiogram on the triage of the patient with acute chest pain. AB - STUDY OBJECTIVE: To determine whether information from a prior electrocardiogram (ECG) improves diagnostic accuracy in the emergency department (ED) evaluation of patients with acute chest pain. DESIGN: Analysis of prospectively collected data from a cohort study. SETTING: Emergency departments of four community and three university hospitals. PATIENTS: 5,673 patients aged greater than or equal to 30 years who presented to the EDs of participating hospitals for evaluation of acute chest pain, including 772 (14%) with acute myocardial infarction (AMI). MEASUREMENTS AND MAIN RESULTS: After adjusting for clinical characteristics, no significant difference was found in the sensitivities of admission to the hospital or to the coronary care unit (CCU) between AMI patients with and without prior ECGs available for review. However, non-AMI patients with prior ECGs available for review were more likely to avoid CCU admission than were non-AMI patients without prior ECGs. This improvement in specificity was most marked in the 2,024 patients whose current ED ECGs had changes consistent with ischemia or infarction: when a prior ECG was available, non-AMI patients were more than twice as likely to be discharged (26% vs. 12%) and about 1.5 times as likely to avoid CCU admission (39% vs. 27%) (both p less than 0.0001). Admission rates of AMI patients with and without prior ECGs were similar. CONCLUSION: When the current ECG is consistent with ischemia or infarction, the availability of a prior ECG for comparison to determine whether the ECG changes are old or new improves diagnostic accuracy and triage decisions by reducing the admission of patients without AMI or acute ischemic heart disease (increased specificity) without reducing the admission of patients with these diagnoses (unchanged sensitivity). PMID- 2231033 TI - Needlestick injuries among resident physicians. AB - OBJECTIVE: To assess the frequency and causes of needlestick injuries in medical and surgical housestaff. DESIGN: A retrospective survey. SETTING: Urban university teaching hospital. PARTICIPANTS: 386 housestaff; 221 responded. INTERVENTION: Survey questionnaire. MAIN RESULTS: 1) Frequency of needlestick: Of 221 respondents, 57 (26%) reported never having had a needlestick, while 164 (74%) reported at least one needlestick injury with a suture or hollow-bore needle. The average frequencies were 0.63 per resident-year among 149 non surgical residents and 3.8 per resident-year among 72 surgical residents. Among residents in internal medicine, 12 of 78 needlestick injuries (15%) sustained were from patients documented to be HIV-positive. 2) Causes of needlestick: The causes of injury were assessed in detail in a sample of the 157 most recent needlestick injuries. Suturing was the cause in 35 of 61 (57%) surgical residents, while recapping needles was the cause in 36 of 96 (38%) non-surgical residents. Inexperience was not the cause of injury; in 94% of cases the residents felt comfortable performing the procedure, and in 74% of cases the residents had performed the procedure more than 50 times before. 3) Reporting of injury: Only 30 (19%) of 157 injuries were reported to the personnel health service, thus compromising documentation for potential workmen's compensation. CONCLUSIONS: Needlestick injuries are common among medical and surgical housestaff. Efforts should be made to prevent needlestick injuries and to report those that occur. PMID- 2231034 TI - Management of asymptomatic chronic aortic regurgitation with left ventricular dysfunction: a decision analysis. AB - STUDY OBJECTIVE: To determine the optimal strategy for the timing of aortic valve replacement in patients with chronic, severe aortic regurgitation with left ventricular dysfunction. DESIGN: Decision analysis comparing early surgery (timed at the onset of left ventricular dysfunction) with delayed surgery (timed at the onset of symptoms) using data from the literature and expert opinion for variables in a representative case scenario (40-year-old man with bicuspid aortic valve disease). SETTING: Tertiary care center doing valve replacement surgery. MEASUREMENTS AND MAIN RESULTS: The early-surgery approach was preferred based on quality-adjusted life years. Sensitivity analysis showed that the result was not affected by the following variables within their derived ranges: rate of symptom development after onset of left ventricular dysfunction for the delayed-surgery approach, perioperative mortality for both approaches, and occurrence of major nonfatal stroke or congestive heart failure for both approaches. Although the decision was sensitive to the yearly postoperative mortality rates, the delayed surgery operative mortality rate had to be almost as low as the early-surgery rate to change the preference to the delayed-surgery approach. The preference could also change if survival were much more important to the patient in the first five years than after five years or if the patient disliked living on anticoagulants enough to value a year on anticoagulants as worth only 80% of a year not on anticoagulants. CONCLUSION: This decision analysis provides quantitative support for the impression that patients similar to the case scenario do better with surgery timed at the onset of ventricular dysfunction than with surgery delayed until symptoms develop. It thus supports the practice of following these patients noninvasively in order to time surgery. PMID- 2231035 TI - Interpretation of graphic data by patients in a general medicine clinic. AB - OBJECTIVE: To assess how patients use graphic data to decide on preferences between alternative treatments. DESIGN: Cross-sectional survey of patients, physicians, and medical students. The physicians and medical students served as a control group with which to compare the patients' responses. SETTING: A university-based Department of Veterans Affairs Medical Center. PARTICIPANTS: 152 patients seen in a general medicine clinic, 57 medical students, and 11 physicians. MEASUREMENTS AND RESULTS: Subjects were given a survival graph showing the patient outcomes for two different unidentified treatments for an unidentified serious disease. They were asked to indicate which treatment they preferred and which portion(s) of the curves most influenced their preference. A large majority of both patients and health professionals preferred the treatment that had worse short-term and better long-term survival. Eleven percent of patients and 51% of health professionals identified mid-curve data (points other than the curve end-points) as most influencing their preferences. CONCLUSIONS: A graphic survival curve appears to provide enough information to assess patient preferences between two alternative treatments. Patients appeared to differ from physicians and medical students in their interpretation of the curves. PMID- 2231036 TI - Expert testimony based on decision analysis: a malpractice case report. AB - OBJECTIVE: Expert testimony in malpractice cases is often subjective and biased. Decision-analytic techniques might provide an objective basis for such testimony. DESIGN: Case report. This article reports the case of a patient with chest pain that resulted in a malpractice suit alleging a delay in diagnosis of coronary artery disease. SETTING: The case occurred in a private practice; the expert witnesses and the decision analysis originated from a university teaching hospital. METHODS: A decision tree and threshold analysis were used to define the thresholds of disease probability at which either testing or treatment should be implemented. The expert testimony of two witnesses that exercise stress testing was the standard of care was compared with the results of the decision analysis. MAIN RESULTS: Decision analysis supported the view that cardiac catheterization would have been the more appropriate test. CONCLUSIONS: Techniques of decision analysis provide a structured and quantitative basis for empirical judgment and may help to minimize current problems with expert testimony. PMID- 2231037 TI - The use of nurses to evaluate houseofficers' humanistic behavior. AB - OBJECTIVES: 1) To determine whether nurse evaluations of humanistic behavior discriminate between houseofficers in an internal medicine training program, and 2) to compare nurse and attending physician evaluations. DESIGN: Prospective, six month comparison of nurse and attending ratings of houseofficer humanistic behavior. PROCEDURE: Using a six-item, Likert-scale humanistic behavior rating form, nurses and ward attendings evaluated 76 PGY-1, PGY-2, and PGY-3 houseofficers over a six-month period. Nurses and attendings voluntarily evaluated houseofficers on all inpatient units in both university and Veterans Administration teaching hospitals. MEASUREMENTS AND MAIN RESULTS: Nurse ratings discriminated residents from one another throughout the six months of the study and over all units in both hospitals. Attending physician ratings were only moderately correlated with nurses' and were significantly more lenient. Exploratory analyses of the nursing evaluations revealed that female houseofficers received significantly more favorable evaluations than did men and that ward nurses were significantly more lenient than were critical care nurses. Nurse ratings did not differ by hospital, training year, or month of evaluation. CONCLUSIONS: Nurses can provide information about humanistic behavior that will allow program directors to discriminate among different levels of houseofficer behavior. Information from nurses differs from that provided by attending physicians. Nurse ratings are affected by gender and by the type of unit from which they are obtained. PMID- 2231038 TI - Residents' attitudes towards and skills in counseling: using undetected standardized patients. AB - OBJECTIVE: To identify the frequency and quality of certain prevention-oriented counseling skills of resident physicians and to compare these skills with the residents' attitudes towards and knowledge about primary prevention. DESIGN: Longitudinal descriptive study. PATIENTS/PARTICIPANTS: 54 PGY-1-3 internal medicine and family practice residents enrolled in three training programs affiliated with Michigan State University's College of Human Medicine. INTERVENTION: Trainees' attitudes towards and knowledge about certain prevention activities were captured by an instrument designed for this study using 127 Likert scales. Counseling skills were assessed with one of two standardized patients. Residents were unaware of the simulation, which occurred in their routinely scheduled ambulatory care setting. Audiotapes of the interactions were rated by blinded, independent raters. Residents had strong positive beliefs about the role of primary care physicians in counseling patients, high levels of knowledge about what the counseling should entail, and high self-assessment about the frequency and quality of their own counseling interventions. Skill levels, however, were at or below a level defined as minimally acceptable. CONCLUSION: Resident physicians' skill levels, as measured in this study, are inadequate to accomplish routine counseling interventions in the primary care setting. These results suggest that more reliance should be placed on direct observation of physicians, ideally in nonreactive settings, for purposes of drawing conclusions about physician performance. Further, these results have implications for the training of students and residents in the area of counseling for prevention. PMID- 2231039 TI - Residents' perception of evaluation procedures used by their training program. AB - OBJECTIVE: To determine the methods of evaluation used routinely by training programs and to obtain information concerning the frequencies with which various evaluation methods were used. DESIGN: Survey of residents who had recently completed internal medicine training. PARTICIPANTS: 5,693 respondents who completed residencies in 1987 and 1988 and were registered as first-time takers for the 1988 Certifying Examination in Internal Medicine. This constituted a 76% response rate. MAIN RESULTS: Virtually all residents were aware that routine evaluations were submitted on inpatient rotations, but were more uncertain about the evaluation process in the outpatient setting and the methods used to assess their humanistic qualities. Most residents had undergone a Clinical Evaluation Exercise (CEX); residents' clinical skills were less likely to be evaluated by direct observation of history or physical examination skills. Resident responses were aggregated within training programs to determine the pattern of evaluation across programs. The majority of programs used Advanced Cardiac Life Support (ACLS) certification, medical record audit, and the national In-Training Examination to assess most of their residents. Performance-based tests were used selectively by a third or more of the programs. Breast and pelvic examination skills and ability to perform sigmoidoscopy were thought not to be adequately assessed by the majority of residents in almost half of the programs. CONCLUSIONS: While most residents are receiving routine evaluation, including a CEX, increased efforts to educate residents about their evaluation system, to strengthen evaluation in the outpatient setting, and to evaluate certain procedural skills are recommended. PMID- 2231040 TI - General internal medicine and technologically less developed countries. AB - OBJECTIVE: To assess the international health activities of departments of medicine, divisions of general medicine, and general medicine faculty and the interest among departments of medicine in joint international health ventures. DESIGN: 15-item, mailed questionnaire. PARTICIPANTS: 100 chiefs of divisions of general medicine associated with training programs in internal medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Completed questionnaires were returned by 87 division chiefs representing 1,355 general medicine faculty. 49% of division had faculty with six weeks' experience in less developed countries. 8.5% of general medicine faculty had six weeks' experience in less developed countries. 7.6% of general medicine faculty were interested in spending extended time in less developed countries. 19% of departments had formal collaborations with schools in less developed countries. 45% of departments were interested in affiliations with U.S. institutions for the purpose of joint international health ventures. CONCLUSIONS: The international health interests of current general medicine faculty may not be satisfied. Departmental and divisional encouragement of international interests would increase the number of U.S. general internists participating in less developed countries. The authors discuss the potential for greater involvement of general medicine faculty in international health. PMID- 2231041 TI - Behavioral complications of dementia: a clinical approach for the general internist. PMID- 2231043 TI - Caring for people with AIDS and HIV infection in hospital-based primary care practice. PMID- 2231042 TI - Cognitive screening tests: an aid in the care of elderly outpatients. PMID- 2231044 TI - Decision making in the management of asymptomatic patients with aortic regurgitation: a cardiologist's perspective. PMID- 2231045 TI - Declining interest in internal medicine residencies: a crisis or a quirk? PMID- 2231046 TI - International health and general internal medicine. PMID- 2231047 TI - IV administration of phenytoin. PMID- 2231048 TI - Racial bias in case presentation. PMID- 2231049 TI - Are physicians obligated to provide preventive services? AB - Preventive care is considered a benefit to the patient. Physicians express a positive attitude towards prevention, but their performance of recommended activities is low, as shown in a five-year trial at the Seattle VA Medical Center. The release of the U.S. Preventive Services Task Force's guide to clinical preventive services has provided physicians with authoritative prevention recommendations. While most physicians are specialists with little interest or skill in preventive care, primary care providers do accept an obligation to provide comprehensive care, including prevention. This paper examines the ethical basis for the idea of obligation. External pressures, legal, economic, and organizational, are affecting the physician-patient relationship in ways that encourage a contract mode of medical practice and limit physicians' ability to provide preventive care. As a profession, medicine needs to speak for the health needs of the public. As practitioners, physicians need to seek the welfare of their patients. PMID- 2231050 TI - Prevention in medical education: an uncertain future. AB - There is reason for pessimism about the incorporation of prevention into medical education. In addition to what might be called the standard reasons for resistance to prevention, there are at least three other structural barriers: the destabilization of the health care system, the loss of interest in careers in primary care, and preventive medicine's failure to adopt a far-reaching critique of medicine and medical education. Only through linkages to progressive health care reform, to primary care, and to the biopsychosocial model can prevention achieve an important place in medical education. PMID- 2231052 TI - Implementation of cancer prevention guidelines in clinical practice. AB - Data from several sources, including consumer surveys, physician surveys, and medical record audits, indicate that consumers do not receive cancer screening tests as recommended by the National Cancer Institute, the American Cancer Society, and the U.S. Preventive Services Task Force. Performance rates are consistently below published standards for all tests except Pap tests. Major reasons physicians do not perform the recommended tests include physician forgetfulness, disagreement with recommendations, lack of time, and patient refusal. Physicians also tend to overestimate their own performance rates. Barriers to screening test performance can be categorized into patient factors, physician factors, test factors, and health care delivery system factors. Interventions, such as computerized reminder systems, physician audits with feedback, and patient education and reminders, can be effective in promoting performance of such screening. Interventions that target both physician and patient may be particularly effective. PMID- 2231051 TI - Background and objectives of the U.S. Preventive Services Task Force. AB - Clinical preventive services have always been recognized by clinicians as an important part of primary care medicine, but for many years there has been some uncertainty as to the effectiveness of these maneuvers in preventing disease and exactly how and when they should be performed. The recent report of the U.S. Preventive Services Task Force provides a comprehensive review of the science base for preventive services and offers specific recommendations for clinicians on the appropriate delivery of screening tests, counseling interventions, immunizations, and other preventive services. The recommendations provide guidance on how to design an appropriate package of services based on the medical history and risk profile of each patient. This article describes the historical background behind the formation of the task force, its methodology and rationale, and the format of the final report, the "Guide to Clinical Preventive Services." The potential implications of this report and its limitations are also discussed. PMID- 2231053 TI - Implementation of preventive services in an HMO practice. AB - Practice does not conform to guidelines unless the guidelines are specifically implemented and performance is monitored. Several examples of implementation in one health maintenance organization (HMO) are given. These include immunization for influenza and follow up of positive screening tests for colorectal and cervical cancer. Each implementation effort has required the development of systems, which in this HMO are automated. Several issues influencing implementation are discussed, including resource constraints and priorities for the allocation of new resources. Developers cannot expect that their guidelines will be incorporated into clinical practice. They must foster specific implementation plans. PMID- 2231054 TI - British perspective on the U.S. Preventive Services Task Force guidelines. AB - The clinical approach to prevention, cogently documented in the Task Force guidelines, implies the medicalization of prevention. The concentration of resources on those most in need is efficient, the widening of physicians' responsibility is welcome, and the influence on the recipients diffuses into the community. The Task Force report, however, fails to stress the problems and the limitations of this approach. The adverse effects of "labeling" can be serious. They need to be measured and taken into account, and there should be no screening without counseling and long-term care; the latter cannot be guaranteed unless there is a comprehensive general practitioner system. Screening readily generates overmedication, particularly since many physicians lack the skills, the inclination, or the staff to provide expert and continuing health advice. Concern for high-risk individuals should be only one part of a much wider preventive strategy. This is illustrated by the close correlations between the prevalence of high-risk status and the population mean value (0.85 for hypertension vs. mean blood pressure, 0.97 for excess use of alcohol vs. population mean intake). The medical approach, important though it is, must not distract attention from the more fundamental population strategy of prevention. PMID- 2231055 TI - Prevention in developing countries. AB - Developing countries have implemented primary health care programs directed primarily at prevention and management of important infectious and nutritional problems of children. Successful programs have emphasized the need for individual and community involvement and have been characterized by responsible government policies for equitable implementation of efficacious and cost-effective health interventions. Unfortunately, developing countries must also face increases in the chronic disease and social problems commonly associated with industrialized countries. Prevention efforts, for example, to reduce tobacco smoking, to modify the diet, to reduce injuries, or to avert environmental contamination, are needed to contain future morbidity and rapidly increasing medical care costs. Developing countries can build on their successful approaches to program implementation and add other measures directed at preservation of health and prevention of disease in adult as well as child populations. PMID- 2231056 TI - The future of disease prevention. AB - The success of curative medical strategies calls attention to a lack in the completeness of health care: disease prevention. Bringing prevention appropriately into health care requires five types of effort: 1) broadening the view of health beyond the medical model to include the environment, social services, and personal health habits; 2) improving the science of prevention; 3) institutionalizing preventive services by relating them to all the participants, from the professionals to the government to the payers to the public; 4) encouraging non-physician health professionals to assume their suitable, possibly majority, share of providing preventive services; and 5) emphasizing preventive services notwithstanding an unevenness of access to them. PMID- 2231057 TI - Evaluating the evidence for the effectiveness of prevention. AB - This report reviews a number of issues that should be considered in evaluating the evidence for the effectiveness of primary and secondary prevention. In evaluating primary prevention, changes in disease incidence are the ideal index but mortality may also be a useful surrogate in certain cases. Both relative risk and attributable risk are valuable concepts in evaluating the benefits of primary prevention. In evaluating screening, the most notable approach to secondary prevention, certain potential biases should be taken into account. These include selection biases due to referral or length-biased sampling, lead time bias, and overdiagnosis bias. An understanding of the methodologic issues involved in evaluating prevention will help ensure the validity of any conclusions drawn regarding the effectiveness of preventive measures and programs. PMID- 2231058 TI - Reflections on the U.S. Preventive Services Task Force recommendations for screening for hypertension and hypercholesterolemia. AB - The U.S. Preventive Services Task Force recommendations for screening for hypertension and high blood cholesterol are generally consistent with preexisting national guidelines promulgated by the Joint National Committee for Detection, Evaluation, and Treatment of High Blood Pressure and the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults. While a welcome addition to the armamentarium of the clinician, the Task Force recommendations represent only a partial solution to our current epidemic of blood-pressure- and cholesterol-related cardiovascular disease. A meaningful reduction in society's burden of cardiovascular disease can be achieved only by complementing the Task Force recommendations with community based mass treatment strategies aimed at shifting the distribution of blood pressure and cholesterol toward a biologically more normal pattern. PMID- 2231059 TI - Breast cancer screening: who should be included? AB - The recommendations of the U.S. Preventive Services Task Force are reviewed in regard to screening for breast cancer. In contradistinction to those issued by some other national organizations, screening for breast cancer using mammography at ages 40-49 is not recommended. It is concluded that the scientific evidence is insufficient at present to recommend mammography screening for women aged 40-49. The recommendations of the task force are: all women over age 40 should receive an annual breast examination; all women should have mammography every one or two years beginning at age 50 and concluding at approximately age 75 unless disease has been detected; and it may be prudent to begin mammography at an earlier age for women at high risk of breast cancer. These recommendations are appropriate in light of the available evidence; though at present there is no evidence that clinical examination of the breasts at any age reduces breast cancer mortality; the upper age beyond which breast cancer screening no longer has a significant effect in reducing breast cancer mortality is unknown; and there is no evidence that women at high risk for breast cancer benefit to a different degree from screening than women not at high risk. PMID- 2231060 TI - Colorectal cancer: have we identified an effective screening strategy? AB - Three currently used screening methods are aimed at detecting colorectal cancer when it is asymptomatic and curable, and at detecting polyps so that they can be removed before they can progress to cancer. Digital rectal examinations are relatively cheap and easy but can detect only a small fraction of large-bowel cancers. Sigmoidoscopy is more sensitive, but its low acceptability to patients has been only partially mitigated by the introduction of the 35-cm flexible instrument. Fecal occult blood testing has limited sensitivity because blood from cancers and polyps is neither continuously shed nor uniformly distributed in feces; specificity and positive predictive value are also low because of other sources of blood in the stool. Prudent judgment suggests that all of these screening tests may prevent death from colorectal cancer in some patients. However, none has been proven effective in general use by well-controlled studies. Case-control studies can provide timely and valuable new evidence in this regard; the authors' investigations in progress are described. The current lack of strong evidence in support of these screening tests should not be interpreted as evidence against their use. PMID- 2231061 TI - The impact of the U.S. Preventive Services Task Force guidelines on cancer screening: perspective from the National Cancer Institute. AB - The U.S. Preventive Services Task Force evaluated the medical literature, utilizing strict criteria to judge the merits of experimental trials designed to show benefit in screening for cancer. For individuals at normal risk, the task force was not able to make recommendations for or against screening for colorectal, prostate, skin, oral, or testicular cancers. Only one physical examination cancer-screening procedure has ever been tested in a randomized trial. During the past 27 years, the National Cancer Institute (NCI) has funded six randomized screening trials. Thus far, only one has shown a decrease in mortality. Recognizing the limitations of such trials, the NCI published "Working Guidelines for Early Cancer Detection." Designed for the practicing physician, these guidelines were based upon the best available evidence and on the judgment of representatives of medical professional organizations. PMID- 2231062 TI - Glaucoma screening: too little, too late? AB - Screening for glaucoma, usually by measuring intraocular pressure, has been popular, but repeated analysis indicates poor sensitivity and specificity. More extensive testing is required. Such testing should be focused on high-risk groups, including blacks and the elderly. Regular comprehensive eye examinations, on a schedule adjusted for these and other risk factors, are probably the most cost-efficient means of identifying patients with glaucoma. The primary care provider has a pivotal role: to encourage patients to undergo such examinations when warranted; and to encourage those on intraocular-pressure-lowering medications to comply with their medication use. PMID- 2231063 TI - Screening for psychiatric and substance abuse disorders in clinical practice. AB - Psychiatric disorders, particularly depression and alcohol abuse, represent a large burden of illness to the society. Many individuals with these disorders receive all of their care from health care providers who are not mental health specialists. There is evidence that non-psychiatric physicians frequently do not recognize these disorders in their patients. Screening questionnaires have been introduced to improve detection of these patients. Several studies have found that these screening questionnaires can increase detection rates, but no important impact on patient outcomes has been demonstrated. This review article outlines several reasons why it has been difficult to discern improvement in patient outcomes: inadequate study design, insufficient physician education, interdependence of psychiatric and medical conditions, and vague treatment guidelines. Practical use of the current psychiatric screening questionnaires and key areas for further investigation are considered. PMID- 2231064 TI - Selective screening: when should screening be limited to high-risk individuals? AB - Issues related to selective screening are discussed. The distinction between test accuracy and program accuracy is presented in the context of impact on cost/true case detection, which in turn reflects the gain in specificity and loss in sensitivity for the total target population. When two or more risk factors are combined to define high-risk subjects, a gain in program accuracy and a relative reduction in cost/true case found ensue if there is additive interaction between these risk factors. The author also discusses periodicity of screening and emphasizes the inappropriateness of using the notion of risk for disease occurrence as a criterion to define periodicity. PMID- 2231065 TI - How serious are the adverse effects of screening? AB - The adverse effects of screening are not commonly studied. False-positive tests lead to discomfort, costs, and risks from additional diagnostic and therapeutic procedures. False-negative tests lead to a sense of security and delays in seeking medical help when symptoms develop. Labeling an individual with a false positive test, or with a true-positive test for which there is no evidence that intervention makes a difference, e.g., intervention on an 80-year-old asymptomatic woman with hypercholesterolemia, can have a markedly negative impact on the quality of life. Interpreting statistical abnormalities out of clinical context, e.g., lending importance to a multiphasic blood screen showing "high" alkaline phosphatase in a teenager, leads to unnecessary costs and anxiety. The cost of screening programs that may not have been shown to do more good than harm is already having an impact on the resources available to diagnose and treatment symptomatic persons. Premature implementation of unproved screening programs will continue to decrease physician and public confidence in prevention. PMID- 2231066 TI - Prevention of cardiovascular disease: risks and benefits of aspirin. AB - Aspirin has been tested for its benefit in preventing cardiovascular disease in randomized trials in three categories of patients. In secondary prevention among those with a history of myocardial infarction (MI), stroke or transient cerebral ischemia, or unstable angina pectoris, 25 randomized trials demonstrated significant reductions from aspirin of 25% for the occurrence of an "important vascular event" (nonfatal MI, nonfatal stroke, or vascular death), 32% for nonfatal MI, 27% for nonfatal stroke, and 15% for vascular mortality. Among those evolving an MI, the Second International Study of Infarct Survival (ISIS-2) showed a significant reduction of 23% in five-week vascular mortality among those started on a one-month regimen of daily aspirin within 24 hours of the onset of symptoms of suspected MI. Aspirin also significantly reduced reinfarction, nonfatal stroke, and important vascular events. Finally, in primary prevention, the US Physicians' Health Study (PHS) showed a significant 44% reduction in the occurrence of a first MI among apparently healthy male physicians; numbers of strokes and vascular deaths were insufficient to permit conclusions for these endpoints. Thus, aspirin is of clear benefit in reducing MI, stroke, and vascular death in secondary prevention and among those evolving an MI. It is also beneficial in the primary prevention of MI among men over 40, but data concerning its effects on stroke and vascular death remain inconclusive. PMID- 2231067 TI - Adult immunizations: are they worth the trouble? AB - There are good data to recommend routine use of vaccines against measles, rubella, tetanus, influenza, and pneumococcal infections in adults. An adolescent or an adult born after 1956 is considered to be susceptible to measles unless he or she has received two doses of live measles vaccine or has suffered a physician diagnosed case of measles. Tetanus is largely a disease of the elderly, and there is a universal need for immunizations with tetanus toxoid. Influenza continues to be a major public health problem, and influenza vaccine should be given annually to the elderly and to those at high risk. The efficacy of pneumococcal vaccine in American adults is still being debated. Results from case-control studies show that the vaccine is about 60% effective in reducing the incidence of disease due to vaccine-related strains. Its use in the elderly and in those at higher risk for pneumococcal infection is recommended. PMID- 2231068 TI - Initiation and maintenance of patient behavioral change: what is the role of the physician? AB - If the physician is to help a patient adopt and maintain "preventive behaviors," the processes that influence and shape both patient and physician behaviors must be understood, the physician's role in the behavioral change process must be acceptable to both the patient and the physician, and an environment that both permits the physician to act and reinforces the physician for acting appropriately must be designed for the physician. A physician's role that is acceptable to both the patient and the physician can be seen as six obligations. The physician must 1) evaluate the medical literature on prevention to determine which services are indicated for which types of patients, 2) when seeing an individual patient, identify the services and behaviors needed by that patient, and 3) advise the patient of the need for action. As the patient responds positively to the physician's advice, the physician must 4) enable and assist the patient to have the indicated tests or procedures and accomplish the suggested behavioral changes, and 5) reinforce the patient's new and ongoing preventive behaviors. The sixth obligation of the physician is to establish, support, and maintain a system to facilitate tasks 2 through 5. PMID- 2231070 TI - Nicotine dependence: a preventable risk factor for other diseases. AB - Nicotine meets all critical criteria for an addictive drug. Furthermore, there is no evidence that there would be widespread compulsive use of tobacco without nicotine. These findings have led to consideration of the cigarette as a contaminated vehicle for an addictive drug (nicotine). Nevertheless, nicotine itself may also be used therapeutically to reduce exposure to carcinogens and other tobacco toxins. Nicotine replacement is a useful adjunct in treating tobacco dependence. For example, nicotine replacement in the form of a polacrilex resin (chewing gum) can alleviate physically based signs and symptoms of tobacco abstinence. The fact that this form of nicotine replacement is not attractive to non-users of tobacco has opened the door to the use of nicotine in a therapeutic modality, permitting hope of eliminating tobacco dependence. PMID- 2231069 TI - The physician's role in injury prevention: beyond the U.S. Preventive Services Task Force report. AB - Injuries and their prevention have received little attention by the medical community, despite the fact that injuries are the leading cause of premature death. However, much can be done to reduce the number and severity of injuries, and the practicing physician has an important role to play in this process. This report outlines the U.S. Preventive Services Task Force report recommendations for prevention strategies to reduce injuries and then seeks to define a broader role for the physician in prevention injuries that extends beyond the confines of office-based practice. While screening and counseling have proven effectiveness in certain situations, interventions that are passive or automatic in action, such as air bags, have proven to be more effective long-term solutions to reduce both the number and the severity of injuries. The author outlines and provides examples of seven areas where physicians can have a major impact either directly or through implementing effective injury-control strategies. These are: treatment, education, screening, hazard identification, research, advocacy, and policy making. Using all of these approaches, physicians can play a truly effective role in reducing the burden of injuries for their patients. PMID- 2231071 TI - Sexual practices: are physicians addressing the issues? AB - The literature suggests that prior to 1981, the only groups concerned with sexual history taking were urologists, psychiatrists, and gynecologists. The appearance of AIDS, however, has made competency in this area of interviewing essential for all primary care physicians. The teaching of sexual history taking presents a challenge to educators, since it involves all three educational domains- cognitive, affective, and skills. The authors have developed an approach to teaching sexual history taking to providers in small groups utilizing videotapes that model the content and sequence of questions and confront learners about the fears and the emotional concerns they may have in obtaining these data. PMID- 2231072 TI - Adolescent pregnancy: the clinician's role in intervention. AB - Adolescent childbearing has adverse sequelae that are intensified when the onset of sexual activity takes place at a particularly early age. A relationship between the onset of sexual activity and the age of maturation has been demonstrated; as the mean age of menarche has become younger, a greater discontinuity has been created between physical development on the one hand and cognitive and emotional development on the other. Initiatives to prevent early sexual initiation and unintended pregnancy must be designed in that context and with an appreciation of normative social pressures. This report reviews research on adolescent development and sexual behavior, including the relationship between maturation and the onset of sexual activity, the timing of pregnancy risk, clinic utilization and reasons for delay in clinic attendance, and clusters of high-risk behaviors. It discusses the role of clinical interventions, suggesting ways in which those who treat adolescents can assist them in acquiring and maintaining protective behaviors. PMID- 2231073 TI - The costs of prevention. AB - A prevention program is cost-effective if it yields more health benefits than do alternative uses of health care resources. Some prevention programs meet this standard: either they actually save more health care resources than they utilize, or their net costs per healthy year of life gained are lower than those of alternatives such as curative or palliative medicine. Other prevention programs, however, are less cost-effective than are medical treatments for the same disease. One lesson for public policy is that generalizations about the cost effectiveness of "prevention" are unwise. Another lesson is that prevention programs should not be subjected to a higher standard than other health programs: they should not be expected to save money, but they should be expected to yield improved health at a reasonable price. PMID- 2231074 TI - Diffusion of the U.S. Preventive Services Task Force recommendations into practice. AB - The U.S. Preventive Services Task Force's "Guide to Clinical Preventive Services" summarizes the results of a critical review of the literature pertaining to the effectiveness of 169 interventions in modifying 60 risk factors or conditions. The ultimate impact of the guide depends on the diffusion into clinical practice of its recommendations. This report reviews the factors influencing the diffusion process. Three categories of behavioral influence--predisposing, enabling, and reinforcing factors--apply to this diffusion process. Predisposing factors include knowledge and attitudes, personal health behaviors, confidence, and beliefs about patients' interests in health-promotion advice. Enabling factors include competence to perform preventive services, reimbursement for preventive services, organization of the practice setting, time to provide preventive services, a reminder system, and a coherent set of guidelines that are perceived as scientific and unambiguous. Reinforcing factors include peer support, feedback, evidence of results, and an enhanced sense of self-efficacy in fulfilling one's role as a healer. Recommendations are given for using these factors to increase the diffusion of preventive services into clinical practice. PMID- 2231075 TI - Changes in pelvic muscle strength and stress urinary incontinence associated with childbirth. AB - Pelvic muscle strength and stress urinary incontinence were studied in 20 nulliparous women at 32 to 36 antepartum weeks and 6 postpartum weeks. Measures used included a digital muscle strength score, observed incontinence, and urine flow interruption. Pelvic muscle strength declined from the antepartum to postpartum periods in women with vaginal births; however, women with greater antepartal pelvic muscle strength tended to preserve a higher level of strength during the postpartum period. In general, less pelvic muscle strength was found in women who demonstrated stress urinary incontinence. PMID- 2231077 TI - Extracorporeal membrane oxygenation and indications for cardiopulmonary bypass in the neonate. AB - Extracorporeal membrane oxygenation (ECMO) is a rescue technique used for term and near-term neonates who have respiratory failure that is unresponsive to conventional therapy. The complexity of the equipment necessitates intensive training of a specialized team before setting up an ECMO unit. An understanding of the physiology underlying ECMO and the criteria used for patient selection assists the nurse in identifying neonates who might benefit from the technique. PMID- 2231076 TI - Incorporating infant stimulation concepts into prenatal classes. AB - Prenatal classes provide an opportunity for childbirth educators to teach couples about parenting, as well as labor and delivery. Infant stimulation concepts can be interwoven into prenatal classes to help facilitate the development of prenatal bonding and parenting skills. PMID- 2231078 TI - Genital herpes. An overview. AB - Data from the National Disease and Therapeutic Index (NDTI) Survey indicate that the number of physician-patient consultations concerning genital herpes increased 15-fold between 1966 and 1984. Because of the increased incidence of genital herpes, the great variance in symptoms and severity of outbreaks, and the frequent misrepresentation of the nature of herpes simplex, all health-care practitioners should receive up-to-date information on the disorder. This article is intended to educate health-care professionals about genital herpes. PMID- 2231079 TI - Relationships between stated feelings and measures of maternal adjustment. AB - Nurses need to identify those women who are experiencing difficulties with maternal-role transition. A study was conducted in which the relationships between women's self-reported feelings during the postpartum period and scores from observational and paper-and-pencil measures of maternal adjustment were explored. The results indicated that self-descriptions of negative physical feelings were related to scores indicating less mothering capability. Self descriptions of negative emotional feelings were related to poorer relationships with husbands, less life satisfaction, and less support for the maternal role. PMID- 2231080 TI - The effect of nipple shields on maternal milk volume. AB - This study was conducted to evaluate nipple shields and determine whether altered nipple shield design would change the amount of milk obtained during breast pumping. The study also sought to determine whether milk volume would change depending on the presence or absence of a nipple shield during breast pumping. Among the 25 participants, pumping without a shield yielded statistically significantly larger milk volumes than pumping with either one of the two kinds of shields evaluated, regardless of the order of nipple shield use. The slight difference in milk volumes obtained when comparing the shields used was not statistically significant. The article includes several questions designed to alert the clinician to the risks of nipple shield use, particularly when the mother and neonate are still learning to breastfeed. PMID- 2231082 TI - Identifying and validating nursing diagnoses in a gynecologic ambulatory-care setting. AB - This descriptive study was conducted to identify the nursing diagnoses made in providing care to 100 gynecologic ambulatory-care patients and to determine the defining characteristics of the three most frequently made diagnoses. Nurse observers studied nurse and patient interactions, recorded the defining characteristics, and assigned a nursing diagnosis to the patient. Twenty-five nursing diagnoses were used in the study, and the type and frequency of the defining characteristics varied. The findings of the study will add to the nursing diagnoses' knowledge base. PMID- 2231081 TI - A community-based approach to the promotion of breastfeeding in Mexico. AB - A comprehensive education strategy is presented that links training, community education, research, and mass-media efforts to enhance breastfeeding practices. Breastfeeding promotion models, an administrative system, and lessons learned during the project are described. The keys to effective breastfeeding promotion are shown to be accurate information; appropriate education, training, and follow up; and a supportive administrative system. PMID- 2231083 TI - Combined Registry for the Clinical Use of Mechanical Ventricular Assist Pumps and the Total Artificial Heart in conjunction with heart transplantation: fourth official report--1989. PMID- 2231084 TI - Heart-lung transplantation for cystic fibrosis and subsequent domino heart transplantation. AB - Between September 1984 and October 1988, 27 patients underwent combined heart lung transplantation for treatment of end-stage respiratory disease caused by cystic fibrosis. The actuarial patient survival was 78% at 1 year and 72% at 2 years. Bacterial respiratory infections were common in the early postoperative period and necessitated vigorous medical therapy. The dose of cyclosporine required in these patients was higher than in conventional transplant recipients, and this contributed to an increased cost of postoperative care. Lung function was greatly improved after transplantation, and long-term survivors achieved an excellent quality of life. Lymphoproliferative disorders developed in two patients; these disorders regressed after a reduction in immunosuppression. Two patients required retransplantation: one because of obliterative bronchiolitis and the other because of recurrent respiratory infections associated with a moderate tracheal stenosis and severe deterioration in lung function. A modification of the technique used for heart-lung transplantation allowed 20 hearts from cystic fibrosis patients to be used for subsequent heart transplantation. Immediate heart function was satisfactory in all cases. The actuarial survival of the recipients of these domino heart transplants was 75% at 1 year. No coronary artery disease was present in the 12 patients who have undergone coronary angiography at 1 year. PMID- 2231085 TI - High-risk heart surgery in the heart transplant candidate. AB - Because of the limited supply of donor hearts, transplant physicians are searching for alternative treatments for patients referred for orthotopic heart transplantation. A group of 20 patients (7% of patients accepted for heart transplantation at Loyola University Medical Center) were nonrandomly sent for conventional heart surgery. Of 20 patients, 17 survived their hospitalization, and 11 of the original 20 have avoided heart transplantation or having their names added to the transplant list. This group represents a high-risk subset of patients. Patients with poor ventricular function and ventricular arrhythmias or with poor ventricular function who underwent first-time revascularization were well served by more conventional heart surgery (all 10 patients survived surgery). Patients with poor ventricular function who required redo bypass operation had a poor result (three of six died), and such patients should be considered carefully for initial heart transplantation. PMID- 2231086 TI - Bridge to heart transplantation: importance of patient selection. AB - Since 1986, 26 candidates were evaluated for mechanical support as a bridge to heart transplantation. Group 1 consisted of 15 patients who were accepted and who received support with a ventricular assist device (14 patients) or a total artificial heart (1 patient). Seven of the 15 patients received transplants and survived, whereas contraindications to transplant developed in seven patients while they were receiving support, and these seven died. One patient remains hospitalized after transplantation. Group 2 consisted of 11 patients rejected for circulatory support because of renal insufficiency or infection (9), pulmonary embolus (1), and cerebrovascular accident (1). Two group 2 patients underwent transplant procedures after their complications resolved, and one survived. One other group 2 patient who recovered without transplantation or mechanical support was discharged. There was no significant difference in age, gender, or cause of cardiogenic shock between the two groups. Four of five patients accepted for mechanical support on the first evaluation survived, and three of 10 accepted after the initial evaluation survived, indicating that delayed selection often results in complications that preclude transplantation and survival. Only one of the 26 patients survived without transplantation or support. These data emphasize the importance of patient selection on the outcome of bridging to transplantation. PMID- 2231087 TI - New technique for intrathoracic heart-lung transplantation in the rat. AB - A technique for intrathoracic heart-lung transplantation in the rat is described. The combined heart and left lung were transplanted into the recipient's thorax in place of the excised left lung. The graft's aorta was anastomosed end to side to the recipient's descending aorta. The bronchial anastomosis was made by the telescoping technique. When the aortic anastomosis was carried out, a total aortic clamp was used in group 1 (26 animals), and an internal shunt was used in group 2 (20 animals). One rat in group 1 and seven rats in group 2 survived with well-functioning grafts for more than 7 days after transplantation. This model of intrathoracic heart-lung transplantation appears to be suitable for investigations of rejection because the grafted lung is ventilated through the anastomosed bronchus. Our internal shunt method makes it possible for this system to be used as an experimental model. PMID- 2231088 TI - Influence of the donor lung on development of early infections in lung transplant recipients. AB - Infection of the lung allograft is the greatest cause of morbidity and mortality after heart-lung transplantation. To better understand the pathogenesis of these infections, we compared the results from cultures of the donor tracheas with the type and prevalence of early intrathoracic infections in the recipients. In the last 37 recipients, intrathoracic infections occurred within 2 weeks of operation in 16 (43%). Organisms isolated from the donor tracheal cultures were different from those associated with early infections, except for three of four recipients with heavy growth of Candida in donor tracheal cultures, in whom fatal invasive candidiasis developed caused by the same species of Candida isolated from the donor culture. Comparisons were made between recipients with (n = 16) and without early infection (n = 21) for age of donors and recipients, ischemic time, length of donor stay in an intensive care unit, donor arterial oxygen pressure, duration of recipient intubation, sterile donor tracheal culture or culture with presence of mouth flora, bacterial pathogens, or Candida, method of lung preservation, and antibiotic prophylaxis of donor. The only factor significantly associated with the onset of early infection was the presence of mouth flora in the donor tracheal culture (p = 0.004, Fisher's exact test, two sided). Multiple logistic regression was performed to test the additional contribution of other covariates after adjusting for the presence of mouth flora. None of the other covariates contributed to the occurrence of early infection. Recipients with early infection had a significantly lower survival compared with those without early infection (p = 0.04) by the Kaplan-Meier survival analysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231089 TI - Natural history of chronic rejection in heart-lung transplant recipients. AB - Chronic rejection is the major cause of death of long-term survivors of heart lung transplantation. Of our 61 patients who have received heart-lung transplants, 29 have been followed up for a year or longer. Seven patients had clinical evidence of chronic rejection within 15 months of transplantations of these seven, four died with postmortem confirmation of extensive obliterative bronchiolitis, interstitial and pleural fibrosis, and vascular sclerosis in the heart and lungs. All seven patients had evidence on transbronchial biopsy specimens of submucosal fibrosis and vascular sclerosis. Twelve of our remaining patients have shown similar areas of lung fibrosis on transbronchial biopsy specimens, and the other 10 are well and without fibrosis seen on transbronchial biopsy specimens. Studies of the 201 biopsy specimens obtained from 29 patients confirmed rejection on 130 occasions, with more frequent, more persistent, and more severe rejection in the chronic-rejection group than in the without-fibrosis or lung-fibrosis group. Opportunistic infections resulted in pneumonia on 19 occasions, and these were most commonly found in patients with lung fibrosis. We conclude that chronic lung rejection is the likely outcome in patients with early, poorly controlled, severe rejection. PMID- 2231090 TI - Comparison of mononuclear cell subpopulations in bronchoalveolar lavage fluid in acute rejection after lung transplantation and Mycoplasma infection in rats. AB - Acute lung rejection after orthotopic left lung transplantation and Mycoplasma pulmonis infection were studied immunohistologically by bronchoalveolar lavage (BAL) in inbred rats using monoclonal antibodies differentiating lymphocyte and macrophage subpopulations. Twenty transplants in a major histocompatibility complex (MHC)-different strain combination (Brown-Norway/Lewis) were examined 2, 4, and 6 days after transplantation. Thirty isotransplants (Lewis/Lewis) and normal Lewis rats were used as controls. Eight Lewis rats with acute Mycoplasma pulmonis infection and six Lewis rats with chronic Mycoplasma infection also underwent BAL. Mononuclear cell subpopulations were analyzed using a panel of monoclonal antibodies to MHC and macrophage differentiation antigens: ED1 monocyte/macrophages, ED2 inflammatory tissue macrophages, OX19 T lymphocytes, and OX12 B lymphocytes. The following results were obtained: (1) All allotransplants developed acute rejection on day 2, and it advanced until day 6, demonstrating severe perivascular and peribronchiolar infiltration of inflammatory tissue macrophages (ED1+/ED2+): (2) the proportion and number of inflammatory macrophages (ED2+) in BAL fluid increased on day 6; (3) in BAL the proportion and number of T lymphocytes (OX19+) increased more prominently than B lymphocytes (OX12+) on day 6 of acute rejection; (4) in infection with Mycoplasma pulmonis the increase of T lymphocytes (OX19+) in BAL was more prominent than that of B lymphocytes (OX12+). In conclusion, serial analysis of macrophage, T- and B-lymphocyte antigens was performed. The increase of the proportion of inflammatory macrophages (ED2+) and lymphocytes (OX19+, OX12+) in BAL fluid occurred rather late in the rejection response. This limits the use of BAL as an early diagnostic method of allografted lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231091 TI - Influence of preoperative transpulmonary gradient on late mortality after orthotopic heart transplantation. AB - We reviewed the transpulmonary gradient, pulmonary arterial systolic pressure, pulmonary vascular resistance (Wood units), and pulmonary vascular resistance index (Wood units X Body surface area), recorded preoperatively in 109 recipients aged 44.6 +/- 13.5 (mean +/- SD) years who underwent orthotopic heart transplantation between March 1984 and March 1988, to identify which measure of pulmonary hypertension most accurately predicts poor outcome after orthotopic heart transplantation. These recipients were followed up as many as 57 (24.7 +/- 14.5) months after their transplant procedure. Preoperative hemodynamic values were as follows: transpulmonary gradient, 10.4 +/- 4.7 mm Hg; pulmonary artery systolic pressure, 53.6 +/- 14.8 mm Hg; pulmonary vascular resistance, 2.7 +/- 1.8 Wood units; pulmonary vascular resistance index, 4.9 +/- 2.7. Nineteen recipients died within 1 year after orthotopic heart transplantation. Causes of death were acute rejection (8), chronic rejection (1), infection (2), nonspecific orthotopic heart transplant failure (4), bowel ischemia (1), pancreatitis (1), lymphoma (1), and liver failure (1). Preoperative pulmonary arterial systolic pressure, pulmonary vascular resistance, and pulmonary vascular resistance index were not predictive of 1-month, 6-month, or 1-year mortality. One-month mortality rates of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg and of those with transpulmonary gradient less than 12 mm Hg were not significantly different (11% vs 3%; p = 0.12). The 6-month mortality rate of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg, however, was five times greater than that of orthotopic heart transplant recipients with transpulmonary gradient less than 12 mm Hg (24% vs 5%; p = 0.003), and 12-month mortality of orthotopic heart transplant recipients with transpulmonary gradient greater than or equal to 12 mm Hg was increased sevenfold when compared with that of orthotopic heart transplant recipients with transpulmonary gradient less than 12 mm Hg (36% vs 5%; p = 0.0005). These results suggest that presently used measures of pulmonary hypertension do not predict mortality in the first month after orthotopic heart transplantation, but that elevated preoperative transpulmonary gradient is associated with a significant increase in mortality at 6 and 12 months after orthotopic heart transplantation. Prospective randomized trials are needed to determined whether extended preload and afterload reduction before and/or after transplant will favorably influence long-term prognosis of orthotopic heart transplant recipients with elevated preoperative transpulmonary gradient. PMID- 2231092 TI - Echo-controlled endomyocardial biopsy. AB - Endomyocardial biopsy is an essential procedure for the diagnosis and grading of rejection in heart transplant patients. Direct control of the bioptome positioning has classically been obtained by fluoroscopy. Starting in June 1988, at our institution an alternative approach involving the use of two-dimensional echocardiography was introduced in clinical practice. In 125 patients 1591 biopsies have been performed: 445 under echographic control and 1146 under fluoroscopic control with 3.6 and 4.5 samples/biopsy, respectively. The percentages of inadequate samples caused by biopsy site sampling were 0.4% and 1.3%, respectively, in the two groups. Cardiac perforation has occurred twice in the fluoroscopic group; it has not been observed in the echographic group. One case of iatrogenic tricuspid regurgitation was detected in each group. We now consider echocardiography the method of choice to guide the bioptome. We prefer it to fluoroscopy because it eliminates the risks of x-ray exposure, increases the number of sampling sites in cases of echocardiographic evidence of rejection, can be easily performed as a bedside procedure, allows choice and variation of sampling sites, and permits monitoring of cardiac complications during and after the procedure. A randomized clinical trial is probably needed to assess with statistical significance the superiority of the echographic-controlled biopsy. PMID- 2231093 TI - Adenosine enhances left ventricular flow during 24-hour hypothermic perfusion of isolated cardiac allografts. AB - Left ventricular flow progressively decreases during preservation of ex vivo hearts by continuous hypothermic perfusion, according to previous studies. This study was done to determine whether left ventricular flow could be maintained during 24-hour hypothermic perfusion by the addition of adenosine to the perfusate. Isolated canine hearts were perfused with either a modified Krebs Henseleit solution or with the control solution containing adenosine (20 mumol/L) for either 4 or 24 hours. On completion of the perfusion period, radioactive microspheres were injected into the arterial inflow of the hearts. Myocardial samples were then taken from the endocardial, midcardial, and epicardial portions of the free wall and papillary muscles of the right and left ventricles, as well as the interventricular septum. Concentrations of radioactivity were determined for each sample, summed, and averaged for each ventricle. The ratio of average concentrations (L/R ratio) was significantly increased in the 24-hour adenosine hearts compared with 24-hour controls (1.10 +/- 0.15 vs 0.64 +/- 0.21, p less than 0.005). The L/R ratio of 4-hour controls (1.30 +/- 0.48) was also greater than that of 24-hour controls (p less than 0.005). These results suggest that left ventricular flow decreases during continuous hypothermic perfusion. The tendency toward diminished left ventricular perfusion after 24 hours is reduced when adenosine is added to the perfusate. Adenosine may be beneficial in ex vivo heart preservation with hypothermic perfusion by improving left ventricular flow. PMID- 2231095 TI - Regeneration of adult human myocardium after acute heart transplant rejection. AB - From August 1984 to March 1989, 1535 endomyocardial biopsy specimens from 79 heart transplant patients were evaluated for rejection. Electron microscopy was performed on 664 of these specimens. Three hundred eighty-eight were diagnosed as accelerating, moderate, severe, or resolving acute rejection. Regeneration of adult human myocardium after acute rejection was seen in 22 specimens. Regeneration was identified in myocytes showing ultrastructural and light microscopic evidence of nuclear division and cytoplasmic dedifferentiation. Regenerating cell nuclei showed complex surface involution and large nucleoli. Cytoplasm appeared embryonic with abundant ribosomes, rough endoplasmic reticulum, and numerous mitochondria. Sarcomerogenesis was associated with cytoplasmic and subsarcolemmal clumps of Z band material. Myofibrillogenesis occurred throughout the cytoplasm but was favored in subsarcolemmal areas. Intercalated discs were primitive and depended on the differentiation state of adjoining myocytes. Nexus junctions were not seen. We conclude that myocyte injury during acute rejection of heart transplants is reversible and that adult human myocytes have a hitherto unsuspected capacity for regeneration. PMID- 2231094 TI - Factors influencing the development of hypertension after heart transplantation. AB - In this study we investigated the factors influencing the development of hypertension in 488 consecutive heart transplant recipients. The cumulative probability of hypertension (blood pressure persistently above 150/95 mm Hg) developing was 52% at 1 year, 67% at 2 years, 73% at 3 years, and 77% at 4 years after transplantation. The incidence was higher in patients receiving cyclosporine and azathioprine compared with those receiving prednisone and azathioprine immunosuppression. The dose of cyclosporine used did not appear to influence the development of hypertension. Intermittent steroid exposure did not increase the incidence in the cyclosporine group. Male transplant recipients and those older than 20 years appeared more prone to the development of hypertension. A family history of cardiovascular disease also increased the incidence. Preoperative and postoperative kidney dysfunction and transplantation because of ischemic heart disease did not appear to affect the incidence of hypertension. Donor characteristics, including the use of hearts from donors who weighed more than the recipients and from patients dying of spontaneous intracranial hemorrhage, did not appear to increase the incidence of hypertension after heart transplantation. PMID- 2231096 TI - Treatment of rejection after heart transplantation: what dosage of pulsed steroids is necessary? AB - Histologically proved rejection after heart transplantation is commonly treated with intravenous steroids, 1 gm/day for 3 days. This regimen may result in severe side effects, however, both metabolic and infectious. In a total of 663 rejection episodes, we treated 397 with conventional steroid therapy, 1000 mg per day for 3 days (group 1), 199 with 500 mg/day for 3 days (group 2), and 67 with 250 mg/day for 3 days (group 3). Response to treatment was assessed by control biopsy after 1 week and graded as ongoing, resolving, or resolved rejection. The efficacy of the three regimens showed no significant differences between the groups as determined by the results of the subsequent biopsy. Ongoing rejection, resolving rejection, and resolved rejection, respectively: group 1-3.3%, 66.5%, 30.2%; group 2-8.0%, 66.8%, 25.2%; group 3-4.5%, 73.1%, 22.4%. We conclude that comparable effects, even with a considerable reduction of pulsed steroids, may be obtained in the treatment of cardiac allograft rejection, if triple-drug immunosuppression is used for maintenance therapy. It seems likely that steroid side effects may be decreased without jeopardizing the graft. PMID- 2231097 TI - Kinking of the pulmonary artery: a treatable cause of acute right ventricular failure after heart transplantation. AB - Kinking of the pulmonary artery has been reported only once as a cause of acute right ventricular failure after heart transplantation. We report two cases of kinking of the pulmonary artery encountered during a 3-year period (120 heart transplants). An analysis of the causes of this complication and a diagnostic and therapeutic approach are presented. PMID- 2231099 TI - Inferior vena caval filters in heart transplant recipients with perioperative deep vein thromboses. AB - Heart transplant recipients may constitute a high-risk group for pulmonary embolism and subsequent complications. We present the cases of two patients who underwent prophylactic filter insertion after deep venous thrombosis developed perioperatively and discuss our rationale for this approach. PMID- 2231098 TI - Azathioprine-related cholestatic jaundice in heart transplant patients. AB - Azathioprine is an immunosuppressive drug occasionally indicted as the cause of some episodes of acute cholestasis. The case described confirms the possibility of acute, severe, and reversible cholestatic hepatopathy of iatrogenic (toxic rather than idiosyncratic) origin. PMID- 2231100 TI - Cyclosporine neurotoxicity in heart transplantation. AB - The neurotoxic potential of cyclosporine in previous clinical experience has not been considered a significant problem. Recently a significant incidence of severe neurotoxicity has been related to cyclosporine therapy in liver transplant recipients. In our heart transplant program we have observed an unexpectedly high incidence of serious neurologic toxicity, presumably caused by use of cyclosporine. Coma, cerebral hemorrhage, hemiparesis and dysphasia, confusion, and visual hallucinations were reported in four patients. Cyclosporine discontinuation or dose reduction eliminated the neurologic effects in all but one patient. Cyclosporine neurotoxic effects should be suspected in heart transplant recipients with central nervous system syndromes. PMID- 2231101 TI - Multidimensional digital image representations using generalized Kaiser-Bessel window functions. AB - Inverse problems that require the solution of integral equations are inherent in a number of indirect imaging applications, such as computerized tomography. Numerical solutions based on discretization of the mathematical model of the imaging process, or on discretization of analytic formulas for iterative inversion of the integral equations, require a discrete representation of an underlying continuous image. This paper describes discrete image representations, in n-dimensional space, that are constructed by the superposition of shifted copies of a rotationally symmetric basis function. The basis function is constructed using a generalization of the Kaiser-Bessel window function of digital signal processing. The generalization of the window function involves going from one dimension to a rotationally symmetric function in n dimensions and going from the zero-order modified Bessel function of the standard window to a function involving the modified Bessel function of order m. Three methods are given for the construction, in n-dimensional space, of basis functions having a specified (finite) number of continuous derivatives, and formulas are derived for the Fourier transform, the x-ray transform, the gradient, and the Laplacian of these basis functions. Properties of the new image representations using these basis functions are discussed, primarily in the context of two-dimensional and three-dimensional image reconstruction from line-integral data by iterative inversion of the x-ray transform. Potential applications to three-dimensional image display are also mentioned. PMID- 2231102 TI - Effect of yellow-tinted lenses on brightness. AB - Magnitude estimates of brightness were obtained for small (5-deg diameter) and large (15 deg X 20 deg) targets viewed through yellow-tinted lenses (ytl's) and luminance-matched neutral lenses. The results indicate that brightness perception with ytl's is up to 40% greater than that with neutral lenses when the spatial extent of the stimulus exceeds the fovea. The onset of the enhancement effect is coincident with the chromatic threshold, and its end point is coincident with psychophysical estimates of rod saturation. In a second experiment, brightness estimates were obtained for the ytl's and neutral lenses during the cone plateau of the dark adaptation curve when rods, but not cones, were desensitized by bleach. The brightness-enhancement effect was negligible. These results confirm the subjective impression that brightness perception is enhanced by ytl's and indicate that this effect is mediated, in large part, by the contribution of rod signals to the chromatic pathway. PMID- 2231103 TI - Spectral sensitivity and adaptation characteristics of cone mechanisms under white-light adaptation. AB - Increment-threshold spectral-sensitivity (ITSS) functions and threshold-versus intensity (tvi) curves were measured under white-light adaptation in rhesus monkeys. The tvi curves showed shape and test wavelength invariance, implying that three cone mechanisms were mediating detection. In general, the results were in agreement with the differential adaptation hypothesis proposed by Stiles that predicted spectral shape invariance of the cone mechanisms but overall changes in the shape of the spectral-sensitivity function with increases in the intensity of the adapting field. The principal changes occurring in the ITSS function as the level of adaptation increased involved a smaller loss in sensitivity of the short wavelength and the long-wavelength peaks compared with the corresponding loss in sensitivity of the middle-wavelength peak. A three-channel model with an opponent L-M mechanism and a nonopponent L-M mechanism (both with S-cone input) and an independent S-cone mechanism described the ITSS data as well as other increment threshold and suprathreshold data. The model values for the ITSS functions, along with parameters derived from the transformation of these data to cone-contrast coordinates, permitted the factoring out of first-site adaptation, second-site adaptation, and the relative strengths of contribution of the L and M cones within the opponent and nonopponent L-M channels. PMID- 2231104 TI - Lightness and brightness over spatial illumination gradients. AB - We extended our studies of lightness and brightness in complex scenes to cathode ray-tube simulations of an array of 35 gray reflective patches under spatially varying illuminants. There were three illuminance profiles, an abrupt step, a linear gradient, and a simulation of side illumination, with nine steepnesses of each. In half the sessions observers adjusted a test patch at one end of the illumination gradient in order to match the lightness of a standard patch at the other end of the gradient. In the remaining sessions they matched the brightness of the test patch to that of the standard. For all three illuminance profiles the lightnesses of the patches matched when they had approximately the same simulated reflectance; i.e., there was excellent lightness constancy even though the illuminance gradients were clearly visible. PMID- 2231105 TI - Perceptual-components architecture for digital video. AB - A perceptual-components architecture for digital video partitions the image stream into signal components in a manner analogues to that used in the human visual system. These components consist of achromatic and opponent color channels, divided into static and motion channels, further divided into bands of particular spatial frequency and orientation. Bits are allocated to an individual band in accord with visual sensitivity to that band and in accord with the properties of visual masking. This architecture is argued to have desirable features such as efficiency, error tolerance, scalability, device independence, and extensibility. PMID- 2231106 TI - Visual artifacts in chromatically subsampled images. AB - Colors sampled in an array of pixels were converted into various luminance chrominance representations, and the chrominance values were spatially subsampled to achieve a compression of the data. For viewing, the chrominance values were reinterpolated and then transformed back to RGB. For each of a range of image types and color spaces, we varied the chromatic sample spacing to determine how much compression would be possible before perceptual artifacts appeared, as determined by a panel of individual viewers. The spacing at which an image was mistaken half the time for a remembered original depended on image content and also on the color representation. Some color spaces, such as hue-lightness saturation, a polar-coordinate color space, are inherently ill suited for chrominance averaging and produce noticeable artifacts on almost any image. Likewise, some images cannot be subsampled satisfactorily, regardless of the color space used. In general, however, images with 16-fold reduction in the amount of chrominance information (that is, a factor of 4 in each spatial direction) are still satisfactory in appearance. PMID- 2231107 TI - Discriminability metric based on human contrast sensitivity. AB - We evaluated a metric for predicting the discriminability of different digitized versions of alphanumeric characters. The metric is based on the assumption that there exists a visual filter such that discriminability is monotonic with the contrast energy in the visually filtered difference between stimuli. To test this hypothesis, we presented two same or different digital versions of a master character and asked subjects to indicate whether the characters were the same or different in a forced-choice procedure with feedback. The filtered contrast energy difference was calculated by convolving the difference between stimulus pairs with filters derived from published human contrast sensitivity functions, following an initial nonlinear transformation of stimulus intensity, and summing the squared result. For some types of stimulus difference, such as contrast quantization errors and Gaussian blurring, performance on discrimination tasks is monotonically related to the contrast energy of the filtered difference vector. The results are consistent with the hypothesis that there exists a single psychometric function that can predict the discriminability of different digitized versions of characters when displayed on various devices. PMID- 2231108 TI - Segregation of basic colors in an information display. AB - Previous studies of the role of color in visual search have shown efficient coding for as many as six colors in a high-density display. In an effort to increase this limit, we established an optimal basic color code from extensive surface-color-naming data. This code yielded excellent segregation in a visual search task: The time required to find a critical target of a cued color increased only marginally as up to nine groups of different colors were added to the display. It made no difference whether the cue was provided by name or by example. Significant color differences in this task triggered a second experiment, which examined the detectability of the critical target feature in the periphery. A close correlation was found to exist in the order of color performance between the two experiments. Color segregation was tested again in a third experiment, in which subjects were required to count the number of targets of the cued color. The colors again segregated well. A final experiment tested the proposition that it was the basic nature of the colors that was responsible for the good segregation. When seven basic colors were pitted against seven equally discriminable nonbasic ones in a modified version of the visual search task, no significant difference was found between the two groups. It is concluded that basic colors segregate well not because they are universally named but because they are well separated in color space. PMID- 2231109 TI - Visual search for color differences with foveal and peripheral vision. AB - Color differences required for fast parallel searches were measured for small and large display fields. The main purpose of the measurement was to test the hypothesis that serial searches obtained with small color differences in large display fields are due to poor discrimination in the peripheral visual field and to the need for foveal fixation. Results do not support this hypothesis but show that the color differences required for parallel search are just as large in a display confined to an area roughly the size of the fovea as in a large display. However, results also show that the color difference required for a fast, parallel search is dependent on the size of the stimuli in a large display field. This result is consistent with the possibility that poor discrimination in the periphery may contribute to the size of the required differences if the stimuli are small. PMID- 2231110 TI - Psychophysics of reading. XI. Comparing color contrast and luminance contrast. AB - Text can be depicted by luminance contrast (i.e., differences in luminance between characters and background) or by color contrast (i.e., differences in chromaticity). We used a psychophysical method to measure the reading speeds of eight normal and ten low-vision subjects for text displayed on a color monitor. Reading speed was measured as a function of luminance contrast, color contrast (derived from mixtures of red and green), and combinations of the two. When color contrast is high, normal subjects can read as rapidly as with high luminance contrast (greater than 300 words/min). Curves of reading speed versus contrast have the same shape for the two forms of contrast and are superimposed when contrast is measured in multiples of a threshold value. When both color and luminance contrast are present, there is no sign of additive interaction, and performance is determined by the form of contrast yielding the highest reading rate. Our findings suggest that color contrast and luminance contrast are coded in similar ways in the visual system but that the neural signals used in letter recognition are carried by different pathways for color and luminance. We found no advantages of color contrast for low-vision reading. For text composed of 6 degrees characters, all low-vision subjects read better with luminance contrast than with color contrast. PMID- 2231112 TI - Characterization of task performance with viewing instruments. AB - Recognition of one military vehicle of a group of six was investigated experimentally as a realistic observation task both for vision through image intensifiers and for thermal viewing devices. It is shown that recognition of real targets is visually equivalent to the detection of a circular disk of a certain size. The size of the equivalent disk is characteristic of the difficulty of the observation task. The image quality of viewing instruments can be related to the size of the disk that can just be detected. This measure of image quality includes resolution, low contrast, low luminance, and noise effects. The effective range of viewing instruments is directly scaled to equivalent-disk size and can be taken as a practical measure of image quality. PMID- 2231111 TI - Reading with fixed and variable character pitch. AB - We compared the effects of fixed and variable (proportional) spacing on reading speeds and found variable pitch to yield better performance at medium and large character sizes and fixed pitch to be superior for character sizes approaching the acuity limit. The data indicate at least two crowding effects at the smallest sizes: one that interferes with individual character identification and one that interferes with word identification. A control experiment using rapid serial visual presentation suggests that it is the greater horizontal compression and consequently reduced eye-movement requirements of variable pitch that are responsible for its superiority at medium and large character sizes. PMID- 2231113 TI - Contrast in complex images. AB - The physical contrast of simple images such as sinusoidal gratings or a single patch of light on a uniform background is well defined and agrees with the perceived contrast, but this is not so for complex images. Most definitions assign a single contrast value to the whole image, but perceived contrast may vary greatly across the image. Human contrast sensitivity is a function of spatial frequency; therefore the spatial frequency content of an image should be considered in the definition of contrast. In this paper a definition of local band-limited contrast in images is proposed that assigns a contrast value to every point in the image as a function of the spatial frequency band. For each frequency band, the contrast is defined as the ratio of the bandpass-filtered image at the frequency to the low-pass image filtered to an octave below the same frequency (local luminance mean). This definition raises important implications regarding the perception of contrast in complex images and is helpful in understanding the effects of image-processing algorithms on the perceived contrast. A pyramidal image-contrast structure based on this definition is useful in simulating nonlinear, threshold characteristics of spatial vision in both normal observers and the visually impaired. PMID- 2231115 TI - Mesopic color matching: some theoretical issues. AB - In this paper I address some theoretical issues concerning the additivity laws of Grassmann as they might apply to color matches in mesopic vision (in which light intensities are such that both rods and cones are active). It is first shown that rods and cones have linearly independent spectral responses, and hence rod and cone spectral responses span a four-dimensional matching space. Next, the iterative tetrachromatic-matching experiment of Trezona [Vision Res. 13, 9 (1973)] is examined for consistency with a four-dimensional Grassmann structure; convergence conditions for the technique are derived and shown to be consistent with the actual conditions of the experiment. Finally, a discussion is presented of the conditions under which mesopic color matching would require only three primaries, even when color matching obeys four-dimensional (but not three dimensional) Grassmann laws. A two-dimensional rod-cone diagram gives significant but not complete insight into the conditions for trichromacy in a four dimensional color-matching space. PMID- 2231114 TI - Image segmentation by object color: a unifying framework and connection to color constancy. AB - A unifying framework is presented for algorithms that use the bands of a multispectral image to segment the image at material (i.e., reflectance) boundaries while ignoring spatial inhomogeneities incurred by accidents of lighting and viewing geometry. The framework assumes that the visual stimulus (image field) from a uniformly colored object is the sum of a small number of terms, each term being the product of a spatial and a spectral part. Based on this assumption, several quantities depending on the reflected light can be computed that are spatially invariant within object boundaries. For an image field either from two light sources on a matte surface or from a single light source on a dielectric surface with highlights, the invariants are the components of the unit normal to the plane in color space spanned by the pixels from the object. In some limited cases the normal to the plane can be used to estimate spectral-reflectance parameters of the object. However, in general the connection of color-constancy theories with image segmentation by object color is a difficult problem. The concomitant constraints on segmentation and color constancy algorithms are discussed in light of this fact. PMID- 2231116 TI - Ophthalmic changes during normal and toxemic pregnancy. PMID- 2231117 TI - Dementia and Alzheimer's disease: resources in Oklahoma. AB - Senile dementia and Alzheimer's disease (often considered a single process) rank as the fourth most common cause of death in the United States and outrank in cost to the nation the three leading causes of death combined. Autopsy studies of patients with the clinical diagnosis of dementia have clearly shown that a wide variety of pathological conditions can produce clinically similar symptomatology. In order to address the many possible causes and treatments of these various forms of dementia, the Alzheimer's Association (formerly known as the Alzheimer's Disease and Related Disorders Association), the Oklahoma Autopsy Assistance Network at the Oklahoma Medical Research Foundation, and The Alzheimer's Foundation (also known as the Familial Alzheimer's Disease Research Foundation) have begun a concerted effort to develop a regional network which can aid patients and their relatives in the diagnosis and management of dementia. Awareness of these organizations by all physicians will help in the development and dissemination of the newer and more specific treatments to patients (and their relatives) with Alzheimer's disease and other forms of dementia in Oklahoma. PMID- 2231118 TI - Rural physician survey. AB - In August 1989, the Physician Manpower Training Commission conducted a survey in an effort to learn what factors influence the recruitment and retention of physicians in rural Oklahoma communities. The results of the survey are summarized in this article. PMID- 2231119 TI - Dural tears associated with lumbar burst fractures. AB - A retrospective review of 817 spinal fracture patients revealed a 7.7% (20 of 258) incidence of dural tears in surgically treated patients. Dural tears were most common in the lumbar burst fractures (10 of 85). Twenty-five percent of patients with lumbar spine burst fractures and a neurologic deficit had a dural tear requiring repair. Eighty-six percent of patients with lumbar burst injuries and dural tears had a neurologic deficit. An initial posterior approach with inspection of the dura and stabilization of the fracture is recommended when treating lumbar burst fractures with a neural deficit. PMID- 2231120 TI - Non-invasive low-intensity pulsed ultrasound accelerates bone healing in the rabbit. AB - The effect of ultrasound (US) on the rate of fibula osteotomy healing in 139 mature New Zealand white rabbits was assessed in this study. Bilateral midshaft fibular osteotomies were made using a 1-mm Gigli saw. US was noninvasively applied to one limb for 20 minutes daily, while the contralateral limb served as a control. A 2.5-cm PZT transducer was applied to both limbs, with the treated limb receiving a 200-microseconds burst of 1.5-MHz sine waves repeated at 1.0 kHz. The incident intensity was approximately 30 mW/cm2. Animals were killed at intervals between 14 and 28 days. Maximum strength increases (significant to p less than or equal to 0.01) ranged from 40 to 85% from postoperative day 14 to 23. On day 28, no significant difference in ultimate strength was noted. From day 17 through day 28, all US-treated fractures were as strong as intact bones (p less than or equal to 0.005). On the other hand, the ultimate strength of the control osteotomies attained intact values only by day 28. These results indicate that biomechanical healing is accelerated by a factor of nearly 1.7. This occurs with an overall acceleration of the healing curve in this fresh fracture model. If noninvasive low-intensity pulsed sine wave ultrasound can significantly accelerate bone repair in clinical application with an in-home treatment of 20 minutes daily, then US may be a useful adjunct for fracture care with a concomitant impact on patient morbidity. PMID- 2231122 TI - Internal fixation of the distal humerus: a biomechanical comparison of methods. AB - Three commonly used configurations of various implants used for fixation of distal humeral fractures were quantitatively compared. The double plate construct, irrespective of plate type (1/3 tubular and/or 3.5 mm reconstruction plate), was significantly stronger, both in rigidity and fatigue testing, than cross screws or the single "Y" plate. If rigid stabilization of supracondylar or bicondylar distal humeral fractures is desired, then two plate constructs, at right angles (the ulna plate medially, the lateral plate posteriorly), are biomechanically optimal. PMID- 2231121 TI - Open reduction and internal fixation of delayed union and nonunion of the distal humerus. AB - Nonunion of a condylar fracture of the distal humerus rarely occurs, but when present it is difficult to manage. We recommend internal fixation of the nonunion in combination with decortication and autogenous iliac crest bone grafting along with careful selection and placement of the implant. Postoperatively, the goal is preservation of elbow motion until the nonunion heals. We reviewed the cases of five patients who had surgery for nonunion of this fracture, all of which healed within 2-3 months after surgery. At final follow-up their average arc of motion was 88 degrees. PMID- 2231123 TI - Supracondylar fractures of the humerus in children: analysis of the results in 142 patients. AB - One hundred forty-two children who had supracondylar humerus fractures and who were treated either by open reduction and internal fixation or by closed methods were reviewed. There were 104 boys and 38 girls. Their ages ranged between 2 and 14 years, with an average age of 8 years. One hundred thirteen of the fractures were of the extension type and 29 were of the flexion type. Sixty-two patients were treated by manipulative reduction and immobilization in a plaster of Paris cast, and 20 were treated by overhead skeletal traction followed by the application of a plaster of Paris cast. The other 60 patients were treated by open reduction and internal fixation. The follow-up period ranged from 4 years to 11 years, with an average of 7.5 years. The results were evaluated based on the range of motion, the subsequent deformity, if any, and the carrying angle. In the overall series we had 72 (50.70%) excellent, 31 (21.83%) good, 13 (9.15%) fair, and 26 (18.30%) poor results. PMID- 2231124 TI - Internal fixation of proximal radial head fractures. AB - The treatment of choice for proximal radial head fractures remains controversial. The goal of any treatment for an intra-articular fracture must be the complete restoration of the joint and its function. Nonoperative treatment leads to full motion in cases of less than 1-2 mm of fracture displacement. Resection of the radial head can be recommended only for very comminuted fractures. All other fracture types should be treated by open reduction and internal fixation. Our own personal follow-up observation of 19 patients who had surgical intervention demonstrated restoration of elbow function after an average follow-up time of 11.7 months. Five patients had a slightly restricted range of motion of less than 10 degrees extension and flexion as well as less than 8 degrees pronation and supination, without signs of arthritis. Because complications were minimal, we recommend internal fixation of displaced proximal radial head fractures to restore the anatomic function of the elbow. This is especially true in cases with accompanying proximal ulna fractures and/or ruptured collateral ligaments of the elbow joint and/or disruption of the distal radio-ulnar joint. PMID- 2231125 TI - Biomechanical and histological evaluation of the Herbert screw. AB - The Herbert screw has been demonstrated to have widespread clinical applicability. A biomechanical and histological evaluation of the Herbert screw was conducted to better define its applications. When subjected to pull-out, toggle, and compression testing, in a cancellous bone calf model, it was demonstrated to be biomechanically inferior to the 4.0 mm ASIF cancellous screw. The use of two Herbert screws minimized but did not eliminate this difference. Articular cartilage healing in a rabbit model was consistently demonstrated if the Herbert screw was buried deep to the osteochondral junction. However, toluidine blue histochemical staining showed that the hyaline-like repair cartilage differed qualitatively from normal cartilage. Utilization of the Herbert screw should include an understanding of the limitations of its fixation potential and a recognition of the repair response after intraarticular applications. PMID- 2231126 TI - Traction force profiles associated with the use of a fracture table: a preliminary report. AB - A load cell was developed that can reliably monitor longitudinal traction forces applied to limbs during several different orthopaedic procedures. This permitted determination of tensile loads and the effects of patient limb positions on tension magnitudes. The relationships between the magnitude and duration of applied tension to functional nerve changes were also studied. This preliminary report reviews traction force data on seven patients for eight operations. Mean peak loads for femoral, tibial, and hip procedures were 686, 356, and 306 N, respectively. Adduction of the limb around a fixed peroneal post caused great increases in traction forces. PMID- 2231128 TI - Ipsilateral fractures of femoral neck and shaft. AB - Thirteen cases of ipsilateral intracapsular femoral neck and shaft fractures were seen. All cases occurred in young adults, with the mechanism of injury in all instances being high-energy trauma. The diagnosis of the femoral neck fracture was missed initially in four cases. The patients were divided into four groups according to treatment protocol: group 1 (two cases), both fractures treated nonoperatively; group 2 (four cases), femoral neck fracture treated nonoperatively, open reduction and internal fixation of femoral shaft fracture; group 3 (three cases), McMurray's osteotomy for femoral neck fracture and internal fixation for the femoral shaft fracture; and group 4 (four cases), open reduction and internal fixation of both fractures. The follow-up period ranged from 6 months to 10.1 years. There was a nonunion of one femoral neck fracture, while all shaft fractures united. The best results were seen in group 4 cases. It is also recommended that routine high-quality X-ray films of the hip should be done in all cases of femoral shaft fracture to decrease the high incidence of missed femoral neck fractures in ipsilateral injuries of the femur. PMID- 2231127 TI - The neglected hip fracture. AB - An untreated fracture of the hip will usually present as a nonunion or a malunion and can present a great challenge to the surgeon. We present our experience with 54 neglected hip fractures, of which 48 had surgical treatment. Malunions were treated with corrective osteotomy. Total hip arthroplasty was used for the older patients with femoral neck nonunions. The younger patients with femoral neck nonunion represented the most difficult problem, and we found valgus osteotomy to be the best procedure for this group. PMID- 2231129 TI - The Partridge nylon cerclage: its use as a supplementary fixation of difficult femoral fractures in the elderly. AB - We report on our early experience with the use of the Partridge nylon cerclage. This system was employed as a supplementary fixation in 18 femoral fractures in elderly patients (average age, 78 years). Indications of its use were reduction of comminuted fragments and enhancement of the grip of the main fixation device on osteoporotic femora or in femora with a prosthesis in situ. All fractures but one healed primarily. At an average follow-up time of 25 months, 15 of the 18 patients were ambulatory. Radiographic review showed that the cerclage did not cause cortical avascularity and that none of the straps used failed. We concluded that the internal fixation of difficult femoral fractures in the elderly can be easily and effectively strengthened by the use of this cerclage system. PMID- 2231130 TI - Fractures of the ipsilateral femur and tibia: emphasis on intra-articular and soft tissue injury. AB - Twenty-one patients with fractures of the ipsilateral femur and tibia were treated at Boston City Hospital from 1982 through 1987. Fourteen (67%) of the 21 patients sustained a total of 17 open fractures (76% of which were grade II or III wounds). Over 50% of the patients suffered concomitant ipsilateral knee injuries. Associated injuries required 37 nonorthopaedic procedures; 30 orthopaedic procedures were required to stabilize the axial skeleton and the other three extremities. Five patients ultimately required amputation, reflecting the magnitude of the initial high-energy trauma. Superior results were achieved when early rigid intramedullary fixation of the femur and rigid stabilization of the tibia with either an intramedullary nail or an external fixator was undertaken. Patients that underwent initial rigid intramedullary fixation of both the femur and tibia required fewer secondary operative procedures than those treated with primary external fixation. Rigid internal fixation allowed for thorough evaluation and treatment of the ligamentous structures of the knee and facilitated management of the soft tissue trauma. PMID- 2231131 TI - Successful use of reaming and intramedullary nailing of the tibia. AB - The records and radiographs of 87 patients with 88 fractures of the tibial diaphysis who underwent intramedullary reaming and nailing were retrospectively reviewed. The mean patient age was 37 years. Seventy fractures were closed, and 18 were open. The indications for nailing were failures of closed treatment (n = 48), nonunions (n = 24), multiple injuries (n = 14), and fixation of osteotomy (n = 2). Seventy-six patients with 77 nails who were followed for an average of 26.2 months were studied. For acute fractures, the average time to complete clinical and radiographic union was 5.3 months. For established nonunions, the average healing time was 9 months. The only fractures that failed to unit were nonunions developing from previously open Type III injuries. Angular deformities greater than 5 degrees did not occur. Significant tibial shortening occurred in only one fracture. Decreased motion in the ankle or knee was present in six patients. Major complications as a result of tibial nailing occurred in three patients: two deep infections and one patellar tendon rupture. Minor complications included 10 patients with pain at the nail insertion site necessitating removal in four patients, three patients with transient sensory peroneal nerve dysesthesias, and one patient with a superficial wound infection that cleared with local care. Nine patients required reoperation. Intramedullary reaming and nailing of the tibia can be used advantageously in the treatment of difficult fractures of the tibial shaft and their sequelae. Attention to the technical details of nail insertion will minimize the most frequent complications. PMID- 2231132 TI - Effects of dynamization after interlocking tibial nailing: an experimental study in dogs. AB - Dynamization of statically locked tibial nails was studied in a canine model. Reamed static interlocking nails were inserted in 16 canine tibiae with unstable osteotomies. At 8 weeks, half were dynamized. At 20 weeks, the tibiae were harvested and studied radiographically, biomechanically, and histologically. Apparent clinical union was present in all tibiae. Complete radiographic bony union was achieved in 13 of 16, with residual radiolucent lines in two tibiae in the static and one in the dynamic group. Biomechanically, dynamization improved stiffness at the fracture site. Histological patterns were similar, but there were trends toward a denser trabecular callus pattern in the dynamized group. The results of this animal study indicate that although dynamization may have a beneficial effect on the quality of early bony healing, static interlocking does not decrease the rate of bony union. PMID- 2231134 TI - Posterior collicular fractures of the medial malleolus. AB - The posterior colliculus of the medial malleolus gives origin to the deep part of the deltoid ligament. Posterior collicular fractures are rare injuries, usually nondisplaced due to stabilization by the tibialis posterior and flexor digitorum longus tendons. This nondisplaced fracture is best identified on external oblique radiographs, which are not usually included in standard ankle views. Thus, some index of suspicion is necessary for their detection. A satisfactory result can be achieved by nonoperative treatment of the posterior collicular fracture. PMID- 2231133 TI - What's in a nail? AB - To determine the incidence of subclinical infection using routine swab methods in asymptomatic patients, 30 consecutive hollow intramedullary nails were studied. Variables identified were leukocyte count and differential, patient complaints, time elapsed from injury to nail implantation, duration of nail implantation, and the size of the nail. Specimens were gathered from the lumen of intramedullary nails using the routine swab method for bacterial culture as well as fungal and acid-fast growth. This material was also subjected to pathologic review with routine hematoxylin and eosin staining. There were no significant positive cultures in this study. The pathologic review indicated that the material in the canal of an intramedullary nail was either granulation tissue, fibrous tissue, or osseous tissue. No patient had a deep or superficial wound infection after implant removal. The results of this study indicate that the material in the lumen of the hollow intramedullary nail will fail to grew organisms when the swab method is used in gathering the specimen or the material is sent for quantitative bacteriology. PMID- 2231136 TI - Volumetric three-dimensional computed tomography for acute calcaneus fractures: preliminary report. AB - Volumetric three-dimensional (3-D) computed tomographic reconstructions were performed on three cadaver specimens before and after fracture for 16 acute calcaneal fractures. This "second-generation" 3-D reconstruction technique produced accurate, detailed images of the extra-articular fracture anatomy. Use of this method provided visualization of specific fracture component displacement otherwise unappreciated prior to surgery. In two cases, vertical splits in the superomedial fragment were demonstrated to best advantage by this 3-D technique. PMID- 2231135 TI - Long-term results of pronation-external rotation ankle fracture-dislocations treated with anatomical open reduction, internal fixation. PMID- 2231137 TI - Fractures of the calcaneal apophysis. AB - Eleven patients with 12 open or closed fractures of the calcaneal apophysis were reviewed. The patterns of fracture varied, although all could be classified by a scheme similar to that used for physeal injuries in the long bones. Open injuries involved young children and were associated with subsequent maldevelopment of the posterior (nonarticular) portion of the calcaneus due to growth mechanism damage. The other susceptible age group, adolescence, had two patients with slipped calcaneal apophysis (type 1 injury), similar to slipped capital femoral epiphysis, and three patients with a splitting fracture through the apophysis and physis into the main part of the calcaneus (type 4 injury). Microscopic physeal injury was also observed in the calcaneus of a fatally injured boy. PMID- 2231138 TI - Remodeling of the skeletally immature distal radius. AB - This case report describes the clinical course of a boy 12 years and 11 months old with the skeletal maturity of an 11.5-year-old, with a distal radial fracture that completely remodeled with 36 degrees of radial and 10 degrees of dorsal angulation. As this case demonstrates, the distal forearm may correct angulation in more than one plane. The remodeling capacity depends on the skeletal maturity of the patient, the proximity of the fracture site to the growth plate, the extent of angulation, and the relationship between the plane of angulation and motion of neighboring joints. PMID- 2231139 TI - Lateral ankle dislocation without fracture. AB - Ankle fracture dislocations are a common entity in orthopaedic practice and their treatment is well documented. Dislocations of other joints are usually treated by closed reduction with a brief period of immobilization. This ankle dislocation without fracture is a rare injury which was treated similarly to other joint dislocations. An intact bony construct of an ankle following dislocation allows for subsequent joint stability when soft tissues have healed. PMID- 2231140 TI - Deficit (14 cm) of the tibia solved by a double sliding graft using the Ilizarov apparatus. AB - A 14 cm deficit of the tibia with a soft tissue deficit was resolved using the apparatus of Ilizarov. The apparatus was applied using a double corticotomy of the proximal and distal remainder of the tibia. The fragments were moved until they met each other in the central part of the deficit. Afterwards, a part of the apparatus was changed (the constructions for sliding grafts were replaced with two new circles). This enabled the compression between the "kissed" fragments, and the space between those fragments and distal and proximal tibial adjacent to the remaining joints was filled by the newly formed bone formation. PMID- 2231141 TI - Putting your reputation in the bank. PMID- 2231142 TI - Facial trauma in women resulting from violence by men. AB - In a 2 1/2-year period, 546 women with facial injuries were treated. In 8.2%, the injury was related to some form of violence exerted by a man. In cases where the individual was known, it was usually the husband or boyfriend (almost 67%). The assault consisted of a beating with the hands in over 70% of the cases. Fracture of the mandible was the most common injury. There were also 62 cases of home accidents. PMID- 2231143 TI - The problem of the bifid mandibular condyle. AB - In a survey of 1,882 prehistoric and historic skulls with 2,077 condyles, 7 double (bifid) mandibular condyles were found. One mandible with bilaterally bifid condyles is presented in detail. Possible causes and consequences of the anomaly are discussed. It is assumed that bifid mandibular condyles with anteroposteriorly situated heads are caused by early childhood fractures, whereas those with mediolaterally situated heads are caused by the persistence of connective tissue septa. PMID- 2231144 TI - Conventional radiographic and computed tomographic findings in cases of fracture of the mandibular condylar process. AB - A total of 40 patients with 46 fractures of the mandibular condylar process were examined an average of 47 months after the injury. The conventional radiologic examination consisted of panoramic radiography and lateral transcranial view of the fracture in the mouth-open and mouth-closed positions. Sixteen patients with 21 fractures of the condylar process were examined additionally by computed tomography (CT) because of temporomandibular joint problems in the sagittal and coronal projection. Computed tomography revealed bony changes in the fractured mandibular condyle and its position in the mandibular fossa more exactly than conventional radiographic examinations. Furthermore, the results showed that disturbances in the position and function of the articular disc may be more common than was earlier anticipated, suggesting the more frequent use of CT examinations to evaluate temporomandibular joint changes after condylar process fractures. PMID- 2231145 TI - Speech, velopharyngeal function, and hearing before and after orthognathic surgery. AB - Articulation, voice, resonance, hearing sensitivity, and middle ear function were examined in 34 patients before and 3, 6, 9, and 12 months after orthognathic surgery. Thirty of the 34 patients had articulation errors before surgery. Errors on the sibilants /s/ and /z/ occurred most frequently, followed by those on /j,zh,ch/ and /sh/. Errors were predominantly distortions with both visual and acoustic components. After surgery, articulation improved spontaneously in the absence of intervention. Most of the preoperative articulation errors were eliminated by 3 months postoperative, but, thereafter, a gradual decline was noted so that by 12 months, errors occurred on /s/ and /z/. Voice, resonance, velopharyngeal port area, and hearing sensitivity were not altered by surgery. This study suggests that severe skeletal malocclusions requiring surgical correction have deleterious effects on the patients' articulation of consonants and that surgical alteration leads to the correction of most of these errors. PMID- 2231146 TI - Evaluation of anterior maxillary alveolar ridge resorption when opposed by the transmandibular implant. AB - Fifteen edentulous patients with complaints regarding denture comfort and/or function were treated with the transmandibular implant. All patients were restored with conventional maxillary dentures opposed by implant-supported removable prostheses. Two to 4 years after surgery, these patients were evaluated for vertical and horizontal maxillary bone loss with a radiographic analysis developed by the authors. With this technique, attention was focused on vertical alveolar ridge resorption in the anterior maxilla. Although the sample size was small, the findings from this study indicate that vertical bone loss in the anterior maxilla does occur when a maxillary denture is opposed by an implant supported overdenture. Comparison of these results with a previous study that evaluated anterior maxillary resorption when a complete maxillary denture opposed natural mandibular anterior teeth and a distal extension removable partial denture demonstrated no statistically significant difference. PMID- 2231148 TI - Facial muscle reanimation using the trigeminal motor nerve: an experimental study in the rabbit. AB - Surgical repair of facial nerve deficits may be marred by lack of muscle control and donor region paresis. Using New Zealand white rabbits, a study was undertaken to evaluate facial muscle reanimation with a donor source not previously used: the motor division of the trigeminal nerve. The results were compared with the severed facial nerve and hypoglossal-facial coaptation. An atrophy scale was calibrated for facial muscles of the rabbit. Clinical, electromyographic, and histomorphometric findings confirmed that the trigeminal nerve was a suitable donor source. The neurorrhaphy produced an exponential rate of repair. PMID- 2231147 TI - Squamous cell carcinoma-antigen for detection of squamous cell and mucoepidermoid carcinoma after primary treatment: a preliminary report. AB - This study evaluated the efficacy of using the periodic measurement of the serum level of squamous cell carcinoma antigen (SCC-antigen) for determining the local recurrence and/or metastasis of squamous cell and mucoepidermoid carcinomas after primary treatment. It was found that at the time of clinical recognition of recurrence, the SCC-antigen level was normal, but metastasis to regional lymph nodes or to remote organs generally was accompanied by an increase of SCC antigen. Changes in the SCC-antigen level with mucoepidermoid carcinoma seemed to be less sensitive than with squamous cell carcinoma. PMID- 2231149 TI - Poly(L-lactide) implants in repair of defects of the orbital floor: an animal study. AB - Because of the life-long presence of alloplastic, nonresorbable orbital floor implants and the complications of their use mentioned in literature, the use of a resorbable material appears to be preferable in the repair of orbital floor defects. A high-molecular-weight, as-polymerized poly(L-lactide) (PLLA) was used for repair of orbital floor defects of the blowout type in goats. An artificial defect was created in the bony floor of both orbits. Reconstruction of the orbital floor was then carried out using a concave PLLA implant of 0.4-mm thickness. At 3, 6, 12, 19, 26, 52, and 78 weeks postoperatively, one goat was killed. Microscopic examination showed full encapsulation of the implant by connective tissue after 3 weeks. After 6 weeks, resorption and remodeling of the bone at the points of support of the implant could be detected. A differentiation between the sinus and orbital sides of the connective tissue capsule was observed. The orbital side showed a significantly more dense capsule than the antral side, which had a loose appearance. At 19 weeks, a bony plate was progressively being formed, and at 78 weeks, new bone had fully covered the plate on the antral and orbital side. No inflammation or rejection of the PLLA implant was seen. PMID- 2231150 TI - Pedunculated soft-tissue mass on the alveolar gingiva. AB - A case of peripheral ameloblastoma, a rare intraoral neoplasm, has been presented. The lesion appears most commonly as a mass on the mandibular lingual gingiva of patients in their fifth and sixth decades of life. The peripheral ameloblastoma does not share the aggressive nature of the intraosseous variant. The lesion has been overtreated in the past and warrants only a local supraperiosteal excision. PMID- 2231151 TI - Paraganglioma of the tongue. PMID- 2231152 TI - Fibrous dysplasia-induced hypocalcemia/rickets. PMID- 2231153 TI - Mucous cell hyperplasia in an odontogenic cyst from a patient with Muir-Torre syndrome. AB - Mucous cell proliferation in a periapical radicular cyst from a patient with a family history of colonic malignancies and multiple sebaceous neoplasms of the skin, so-called Muir-Torre syndrome, is reported. Such goblet cell hyperplasia has not been previously reported to be associated with any known syndrome. We believe the finding of mucous cell hyperplasia in an odontogenic cyst may not simply be coincidental, but should raise suspicion of paraneoplastic potential and warrant further evaluation for possible occult neoplastic disease. PMID- 2231154 TI - Metastatic leiomyosarcoma of the palate. PMID- 2231156 TI - Adaptation to mental nerve anesthesia. PMID- 2231155 TI - Nasal-vestibular drainage systems for infections of the maxilla. PMID- 2231157 TI - Effect of undercut placement on crown retention after thermocycling. AB - The aim of this study was to examine the effect of undercuts in castings and/or tooth structure on the retention of crowns luted with glass ionomer cement. After routine full-crown preparations had been made in 48 human premolars, wax patterns were fabricated for each tooth. Retentive coves were then produced with a round bur in either the tooth structure or the wax patterns, or in both. One group of teeth and patterns did not receive any undercuts; this was the control group. Castings were made in non-precious metal. All crowns were luted with glass ionomer cement. Half of the samples were thermocycled, and the remainder were kept at 37 degrees C. Crowns were removed using tension (0.012 cm min-1) and the mean bond strengths calculated. The differences in retentive strengths were tested for statistical significance using ANOVA and Scheffe's test. The presence of coves in castings and/or tooth structure significantly increased the retentive strength of castings cemented with glass ionomer, as compared with conventional crown preparations without retentive undercuts. The effect of thermocycling on the retentive strength of castings cemented with glass ionomer was not statistically significant. PMID- 2231158 TI - A potential MRI hazard: forces on dental magnet keepers. AB - The objective of this study was to determine the forces on dental prosthetic magnet keepers, with a view to assessing the potential for patient injury during magnetic resonance imaging (MRI). Four pre-formed keepers and one castable keeper alloy were tested. Magnetizations and high field susceptibilities were determined for each of the five specimens using data from a vibrating sample magnetometer. The magnetic field intensity with respect to distance from the main magnet coil was obtained from the manufacturer (1-5 tesla General Electric Signa Imaging System). A plot of force versus distance from the main coil and the maximum force at the magnet portal was determined for each specimen. The maximum forces ranged from 0.12-0.24 N for the pre-formed keepers and 3.67 MNm-3 for the castable alloy. It was concluded that the risk of patient injury by displacement is minimal, if the keepers are properly attached to supporting structures. PMID- 2231159 TI - Nocturnal bruxing events in healthy geriatric subjects. AB - Thirty healthy geriatric subjects were studied during a single night of sleep in a sleep laboratory. Unilateral masseter muscle activity was recorded in addition to the standard polysomnographic study. The geriatric subjects in this study exhibited fewer bruxing events than other subjects reported in the literature. Certain conditions that have not been previously investigated, such as sleep position, type of bruxing event, and relationship to the state of the dentition, are reported. PMID- 2231160 TI - Electrical potentials of restorations in subjects without oral complaints. AB - The electrical potentials of 183 amalgam and 11 precious metal restorations, and one set of brackets, were measured. None of the 28 subjects had galvanism, leukoplakia, oral lichen planus, or toxic or allergic reactions to restorations. The potentials of the amalgam restorations increased with age, from about -350 mV NHE at 30 days, to about +100 mV NHE after more than 1000 days. In most subjects potential differences of more than 50 mV were present between restorations; this phenomenon is therefore assumed to be common in healthy populations. PMID- 2231161 TI - Retention of denture adhesives--an in vitro study. AB - Denture adhesives are being used by patients to aid the retention and stability of their dentures. A number of laboratory and clinical investigations have been conducted to study the effects of such adhesives. This study describes a simple in vitro method for measurement of their retentive effect and its relation to loss of adhesive. The results show that there is a reduction in the effectiveness of adhesives, and that there is also an increase in adhesive loss, with time. There appears to be a correlation between these two properties. PMID- 2231162 TI - Further studies of mandibular movement at initial tooth contact. AB - By measurement of movement of the mandible immediately after tooth contact during tooth tapping tasks, it has been shown that patterns of direction are less regular in bruxist subjects than in non-bruxist individuals. The qualitative differences in these patterns are more apparent than the quantitative ones in both cessation and commencement of movement. PMID- 2231163 TI - The effects of an occlusal splint on the electromyographic activities of the temporal and masseter muscles during maximal clenching in patients with a habit of nocturnal bruxism and signs and symptoms of craniomandibular disorders. AB - The effects of a full arch maxillary plane occlusal splint on the level of electromyographic (EMG) activity in the anterior temporal and masseter muscles during maximal clenching were studied in 31 patients with a habit of nocturnal bruxism and signs and symptoms of craniomandibular disorders, before and after occlusal splint therapy. The results showed, before treatment, that the occlusal splint changed significantly (in 71% of patients) the level of EMG activity during maximal clenching. However, these changes were not consistent and differed between patients and even, in some patients, between muscles. After long-term occlusal splint therapy and improvement of the signs and symptoms of craniomandibular disorders, the number of patients who had an identical level of EMG activity during maximal clenching in the intercuspal position and on the occlusal splint tended to increase. Moreover, in these patients the level of symmetry of action in pairs of muscles during maximal clenching was strong, and the splint did not change this level of symmetry. PMID- 2231165 TI - Clinical oral test for the assessment of oral symptoms of glossodynia and glossopyrosis. AB - Subjective oral symptoms of a burning sensation and pain in the tongue may exist in the absence of any pathological changes in the oral mucosa. Owing to different treatment approaches and the lack of any specific therapy, it appeared potentially useful to identify these subjective symptoms by means of a test for an improved therapy evaluation. In this study, we have attempted to develop a method for the objective assessment of oral symptoms of glossodynia and glossopyrosis, by recording the local temperature. The temperature of the tongue was determined using a DT-1 electron thermoesthesiometer, that was highly sensitive to temperatures between 36 degrees C and 38 degrees C. Measurements were performed in topographic areas recommended by the World Health Organization in 1980. The study sample consisted of a group of 50 patients with glossopyrosis and glossodynia, without any clinically manifest pathological changes in the oral cavity, who were compared with a group of 50 age- and sex-matched subjects free of these oral symptoms and with normal oral mucosa. Statistically significant temperature differences were observed between the patients and the controls, as measured in seven different areas. The lowest temperatures (33 degrees C) were measured in the apex linguae area. The minimum temperature was significantly lower in the study group. Significant differences in temperature were also observed between the sexes. It was concluded that glossodynia and glossopyrosis, both inflammation and diminished circulation without any visible clinical signs, can be diagnosed using the thermoesthesiometry test. Such an objective test allows appropriate therapeutic treatment to be selected for patients with the above-mentioned symptoms. PMID- 2231164 TI - Dental cutting behaviour of mica-based and apatite-based machinable glass ceramics. AB - Some recently developed industrial ceramics have excellent machinability properties. The objective of this study was to evaluate the dental cutting behaviour of two machinable glass-ceramics, mica-containing Macor-M and apatite- and diopside-containing Bioram-M, and to compare them with the cutting behaviour of a composite resin typodont tooth enamel and bovine enamel. Weight-load cutting tests were conducted, using a diamond point driven by an air-turbine handpiece, While the transverse load applied on the point was varied, the handpiece speed during cutting and the volume of removal upon cutting were measured. In general, an increase in the applied load caused a decrease in cutting speed and an increase in cutting volume. However, the intensity of this trend was found to differ between four workpieces. Cutting Macor-M resulted in the second-most reduced cutting speed and the maximum cutting volume. Cutting Bioram-M gave the least reduced cutting speed and the minimum cutting volume. It was suggested that two machinable glass-ceramics could be employed as typodont teeth. This study may also contribute to the development of new restorative dental ceramic materials, prepared by machining. PMID- 2231166 TI - [Prognostic significance of the DNA ploidy of the early glottic cancer]. AB - The stage classification is most frequently used at the present in predicting the outcome of laryngeal carcinoma. Recently, DNA ploidy pattern as detected by DNA flow cytometry and cytofluorometry has been also shown to be predictive. In this study, DNA cytofluorometry was performed on formalin-fixed paraffin-embedded tissues from 18 patients with T1 and T2 glottic squamous cell carcinoma for whom long-term follow-up data were available. The DNA ploidy pattern was classified into three types, diploid, diploid + tetraploid and aneuploid according to the DNA content of Go/G1 cells and mitotic cells. In these 18 cases, 8 cases (44%) had diploid pattern, 3 cases (17%) had the diploid + tetraploid pattern and 7 cases (39%) had the aneuploid pattern. The ploidy pattern was significantly associated with the relapse-free rate, but did not correlate with the stage of the carcinoma and differentiation of the cancer cells. Distribution of the patients by histology, stage and therapy was almost equal among the diploid, diploid + tetraploid and aneuploid groups. All the patients were treated with irradiation (60Gy). In the group as a whole, no patient died of glottic carcinoma. Relapse-free survival rates for diploid, diploid + tetraploid and aneupoid were 88%, 33% and 29% respectively. This retrospective study of glottic cancer treated with radiation therapy suggests the possibility that the DNA ploidy pattern would significantly predict patient outcome and would be useful for selecting patients whose poor prognosis demands more aggressive therapy. PMID- 2231167 TI - [Changes of the threshold level in patients with 22-channel cochlear implant]. AB - Psychophysical responses of the patients to electrical stimulation were examined in order to clarify long-term effects of the cochlear implant in 9 patients who had received a 22-channel cochlear implant. Measured items were the minimal threshold level (T-level), the maximum comfortable level (C-level), and the dynamic range between T- and C-level. Measurements were repeated for each electrode every three months over more than 6 months. Following results were obtained. 1) The changes of the T-level were classified into four types as follows, a type with no change, a type with gradual decrease, a type with decrease in two to three months followed by gradual increasing threshold and a type with gradual increasing just after surgery. Even in a last type, the maximum increase in the T-level did not exceed 200 microA and, in most cases, these changes were stabilized within a few months after implantation. 2) The dynamic range gradually increased. It was obvious in both in the middle and apical electrodes, while such increased threshold was not observed in the basal electrodes. 3) In some cases, a few basal electrodes could not been used since they caused uncomfortable sensation or those dynamic ranges became below a certain extent. As a result, it was suggested that the electrical stimulation had not induced serious degeneration of the ganglion cells and the auditory nerve fibers. The reduction in the number of usable electrodes might be due to the surgical trauma to the intracochlear tissue. Therefore, exposing of the scala tympani should be minimal in order to avoid the damage of the cochlea. PMID- 2231168 TI - [Epidermal growth factor in cholesteatoma--the first report: the localization in the cholesteatoma tissue]. AB - The localization of epidermal growth factor (EGF) in human cholesteatoma tissue was examined immunohistochemically, using sections of formalin-fixed, paraffin embedded tissue with avidin-biotin peroxidase complex method. Thirty-three cases of active cholesteatoma which had abundant granulation and debris were studied. Out of 33 cases, EGF was positive in 32 cases (97%) in the epidermis, 30 cases (91%) in the fibroblast, and 21 cases (64%) in the endothelial cells. In 9 cases of inactive cholesteatoma, on the other hand, EGF was positive in 5 cases (56%) in the epidermis, no case in the fibroblast, and a case (11%) in the endothelial cells. Active cholesteatoma had higher immunoreactivity in the epidermis than inactive cholesteatoma. This suggests that the activity of cholesteatoma is indicated by the immunoreactivity of EGF. Difference of EGF immunoreactivity between active and inactive cholesteatoma was bigger in the fibroblast in the subcutaneous tissue of cholesteatoma than in the epidermis. This gives the reason that the activity of cholesteatoma exists in the subcutaneous tissue. These results suggest that EGF plays an important role in accelerating the growth of cholesteatoma. PMID- 2231169 TI - [Epidermal growth factor in cholesteatoma--the second report: the localization in the horny layer]. AB - The localization of epidermal growth factor (EGF) in human cholesteatoma tissue, normal ear drum and external auditory canal skin was examined immunohistochemically, using avidin-biotin peroxidase complex method. Bouin-fixed tissue was stained for investigation of horny layer in the epidermis, because fixation in Bouin's solution provides better preservation of the antigen. In the horny layer of cholesteatoma tissue, 19 out of 24 cases had EGF-positive immunoreactivity (79%). In 2 cases of normal external auditory canal skin, 4 cases of normal ear drum and a case of postauricular skin, no EGF immunoreactivity was revealed in the horny layer. EGF was assayed in the debris of cholesteatoma and the horny layer of the normal bony external canal with dot blot immunoassay. EGF content of the debris was higher than that of the horny layer of normal skin. The result of the first report suggests the activity of cholesteatoma exists in the subcutaneous tissue (see the previous paper). In this report EGF content of cholesteatoma in the horny layer was found higher than that of normal external skin. This result demonstrates that EGF in the horny layer plays an important role in accelerating the growth and bony destruction in cholesteatoma. To summarize these two reports, the following conclusion was reached. In the epidermis EGF content is equal in cholesteatoma and normal skin. But in the subcutaneous tissue and the horny layer EGF content of cholesteatoma is higher than that of normal skin. EGF in situ may be strongly related to the growth and bony destruction of cholesteatoma. PMID- 2231170 TI - [Allergen skin tests to insects, chironomid, caddis fly and silkworm moth, in patients with nasal allergy]. AB - The present study was undertaken to assess the importance of insects as allergens causing nasal allergy. We performed intradermal skin tests with extracts from three insects, chironomid, caddis fly, and silkworm moth, on patients with nasal allergy and on volunteers among medical students. Twenty-two (27.5%) of 80 nasal allergic patients showed positive reactions to chironomid allergen and 9 (11.3%) had positive reactions to caddis fly allergen and 18 (22.5%) to silkworm moth allergen. These positive rates were as frequent as those to Candida or ragweed. Medical students were divided into two groups, symptomatic and asymptomatic, according to the presence or the absence of nasal allergy. Three (11.5%) of 26 symptomatic group showed positive reactions to chironomid and one (3.8%) to caddis fly and 5 (19.2%) to silkworm moth. While even 4 (8.3%) of 48 asymptomatic group showed positive reactions to chironomid, 2 (4.8%) to caddis fly, and 6 (12.5%) to silkworm moth. These results suggested that these insects, chironomid, caddis fly, and silkworm moth, are relatively common than we expected and suspected as important allergens in nasal allergy. PMID- 2231171 TI - [An ultrastructural study on the regeneration of blood vessels of the curetted tracheal mucosa in rat]. AB - After the respiratory tract is damaged by trauma or infection, it is repaired rapidly. The purpose of this study is to observe morphologically the regenerative process of tracheal mucosae, especially the regeneration of blood vessels in the mechanically injured tracheal mucosa of rats. The total mucosal layer of trachea was removed by curetting in 95 adult rats. Then, at several interval from one hour to ten weeks after treatment, 5 rats were killed, and their curreted area of the trachea were removed as specimen for transmission electron microscopical and scanning electron microscopical observation. For scanning electron microscopy, vascular network casts were made by the infusion of Mercox resin through the aortic arch. One hour after curetting, the injured blood vessels formed terminal blind branches. From three hours to one week after curetting, many vascular bud like-processes appeared in venules at the floor and margin of the curetted wound. Twelve hours after curetting, new vascular network were observed in the curetted area. One week after curetting, the vascular network was consisted of capillaries, veins, and arteries. The vascular networks were almost completely rearranged at six weeks after curetting. However the irregular arrangement were still observed partially after ten weeks of curetting. The formation of terminal blind branches in vessels were noted as the initial healing process of injured vascular networks. Then many "bud-like-processes" appeared. Six weeks after curetting, the vascular networks were almost completely rearranged. PMID- 2231172 TI - [A case of epipharyngeal tuberculosis with tuberculosis otitis media]. AB - A 23-years-old female with no known previous contact with tuberculosis complained of right otorrhea. Treatment with antibiotics agent was resisted, and a tympanic perforation became two. Her tuberculin test was positive, but her chest X-ray showed no signs of lung tuberculosis. Posterior rhinoscopy revealed a granuloma in the epipharynx. Histological examination of a biopsy specimen revealed tuberculosis changes. Treatment with antituberculosis agents, SM.INH.RFP greatly reduced the mass and the tympanic perforation. PMID- 2231173 TI - [The histologic study of the inner ear in guinea pigs on anaphylatoxin]. AB - Complement is known to relate to many inflammatory reactions. C4a, C3a and C5a, known as anaphylatoxins, are known to cause strong inflammatory reactions. In this study, the role of anaphylatoxins on the pathogenesis in the cochlea was examined. On hundred forty six male Harley guinea pigs, weighing about 350 grs, all susceptible to preyer's reflex, were used in this study. Anaphylatoxins were made from guinea pig serum treated with zymosan, and inoculated into the carotid artery of the guinea pigs. Parts of these animals were sacrificed and examined at ten minutes, one day, two days, three days, seven days, ten days and fifteen days after injection of anaphylatoxins. Pathological changes in inner ears were observed by light microscopy. After 10 minutes, inner ears were found morphologically normal. After one day, inner ears were found to be almost morphologically normal but the stria vascularis was observed with cystic formation. After two days, cystic formations in the stria vascularis were enlarged and Reissner's membranes were collapsed in some other animals. After three days, the stria vascularis in the various cochlear turns except in the basal turn, were extremely atrophied, some cochlear nerves showed degeneration and some cochlea showed endolymphatic hydrops. After seven days, ten days and fifteen days, the morphological changes showed atrophy in the stria vascularis similar to the results observed on the third days. Atrophy in the stria vascularis was improved gradually with time, but the degeneration of the cochlear nerve was not improved. Opinions have been divided on the cause of inner ear disease including Meniere's disease. Many authors have reported that infectious diseases, for example mumps, measles and cytomegalovirus infection, have caused human sensorineural hearing loss. These diseases have been reported to result in atrophy in the stria vascularis, degeneration of the cochlear nerve and some other pathological changes. In this study, it was clearly observed that the atrophy of the stria vascularis, the endolymphatic hydrops and other morphological changes were caused by introduction of anaphylatoxins. These results were similar to the pathological changes observed in inner ear diseases in human beings. Therefore, inflammatory substances, including anaphylatoxins, were closely related to the cause of inner ear diseases. The animal model used in this report is considered to be important for elucidating the pathogenesis of inner ear diseases. PMID- 2231174 TI - [Effects of uvulopalatopharyngoplasty in adult patients with obstructive sleep apnea syndrome]. AB - We performed uvulopalatopharyngoplasty (UPPP) in 51 adult patients with obstructive sleep apnea syndrome (OSAS). After UPPP, there were statistically significant improvements in apnea-hypopnea index (AHI), the lowest value of oxygen saturation during sleep and total time of apnic episodes. 28 patients (54.9%) were good responders who represented more than 50% improvements in their AHI. Poor responders tended to be more severe and older than good responders. After cephalometric analysis, poor responders were revealed to show significantly poor mandibular prognatism and also lower positioned hyoid bone than good responders. PMID- 2231175 TI - [Pathohistological study on active endolymphatic hydrops in guinea pig--with stress stimulations]. AB - Recently Meniere's disease is believed to show a pathological features of endolymphatic hydrops, but the etiology of this disease has not yet been ascertained. Many investigators tried to create animal models with endolymphatic hydrops by obliterating endolymphatic sac and duct. However, these methods have not been adequate to explain the mechanism of development of Meniere's disease, because it gives mechanical damage to destroy endolymphatic sac and duct. On the other hand, Meniere's disease is thought to develop even as a result of stress. The present paper reported the conduction of an acute experiment, creating active endolymphatic hydrops by stress load, to study the occurrence rate of endolymphatic hydrops and the pathological findings of inner ears by a light microscope. This was followed by a light and electron microscopic study on the changes in permeability of the cochlear lateral wall with horseradish peroxidase and a study of the development mechanism of endolymphatic hydrops. Results obtained were as follows: 1. Although it was impossible to cause endolymphatic hydrops with a single stimulation, four kinds of stress stimulations could cause endolymphatic hydrops with the rate of 37.8%. 2. Judging from the different pathological findings between the group with four kinds of stress stimulations and the untreated control group, vessel permeability in the stria vascularis was highly changeable, while that in the spiral ligament was not. 3. It was found out that increased permeability of the stria vascularis vessels was by increased pinocytotic vesicular transport and through tight junctions from vessel lumen to basal lamina and that it was presumably only by increased pinocytotic vesicular transport beyond basal lamina. 4. It was assumed that increased permeability of the stria vascularis vessels was one of the causes of endolymphatic hydrops which were believed to be pathological features of Meniere's disease. PMID- 2231176 TI - Conduction in the giant nerve fiber pathway in temperature-sensitive paralytic mutants of Drosophila. AB - To study electrogenic conduction in neurons of the cervical giant nerve fiber (CGF) pathway in Drosophila adults carrying temperature-sensitive paralytic mutations that affect sodium channels, we recorded dorsal longitudinal muscle (DLM) responses evoked by electrical stimulation of the brain. In the mutants tipE, napts and parats, conduction in certain neurons presynaptic to the CGF failed at about the same temperature at which paralysis occurred in each mutant. Conduction in the CGF and neurons postsynaptic to it remained active in all mutants even at very elevated temperatures. In contrast, analysis of sei mutants showed enhanced spontaneous activity at elevated temperatures in at least some neurons of the CGF pathway. The implications of these results with respect to the normal in vivo functions of these genes in neuronal signalling are considered. PMID- 2231177 TI - Cell loss in the inferior olive of the staggerer mutant mouse is an indirect effect of the gene. AB - Staggerer (sg) is an autosomal recessive mutation in mouse that causes severe cerebellar atrophy. In this mutant, the Purkinje cell (PC) number is reduced by about 75% and the remaining Purkinje cells have a reduced dendritic arbor and an ectopic location. Previous analysis of staggerer chimeras has demonstrated that the Purkinje cell phenotypes are all direct consequences of the cell-autonomous action of the staggerer gene. The two major afferents to the Purkinje cell are also affected. Virtually all of the granule cells die by the end of the first postnatal month. This death, however, has been shown to be an indirect consequence of mutant gene action. The second major afferent system is from the cells of the inferior olive that project to the main trunks of the Purkinje cell dendrite via the climbing fiber system. Quantitative studies of cell number in the inferior olive have shown that the number of cells is reduced by about 62% in adult sg/sg mutants. We report here the results of our quantitative analysis of three staggerer chimeras. beta-glucuronidase activity was used as an independent cell marker. Our findings demonstrate that inferior olive cell death in staggerer mutant mice is an indirect effect of staggerer gene action. Thus, as for the granule cells, the loss of olivary neurons most likely results from a target related cell death. PMID- 2231178 TI - Detection of a case of pseudolymphocytosis due to cryoglobulins. AB - A new type of interference of cryoglobulins on hemocytometric tests is described. The precipitation of temperature-dependent proteins produced a pseudolymphocytosis on a three-part differential leukocyte count of Coulter S Plus VI, whereas unaffected results, identical to the microscopical count, were obtained using the cytometer Coulter VCS. The laboratory detection of cryoglobulin interference on hematological data is very important in patients with underlying diseases, where the accuracy of absolute and differential leukocyte counts is critical for follow-up. Histograms from the Coulter S-Plus VI can help detect these cases. PMID- 2231179 TI - An ELISA procedure to detect anti-double-stranded and anti-single-stranded DNA binding antibodies in connective tissue disorders. AB - A simple and sensitive enzyme-linked immunosorbent assay (ELISA) is described for the measurement of antibodies to native DNA (double-stranded) and to heat denatured DNA (single-stranded) in sera of patients with connective tissue disorders. DNA bound to polyvinylchloride plates is incubated with serum samples, and antibodies to both single- and double-stranded DNA are detected by means of goat antihuman IgG alkaline phosphatase conjugate. The binding in individual sera is expressed as binding units per milliliter and refers to the absorbance in relation to the absorbance value obtained with a set of standards. The various parameters of the ELISA assay are described, and the results are compared with results of the Crithidia and Farr DNA antibody assays. Two case reports are discussed. PMID- 2231180 TI - Myeloid leukemia differentiation by phorbol ester and retinoic acid: a practical approach. AB - The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and RA (retinoic acid) were investigated on the cell lines HL60 (acute promyelocytic leukemia) and K562 (erythroleukemia) and on cells from patients with several kinds of leukemia. There were 14 cases of acute lymphocytic leukemia (ALL), 2 cases of chronic lymphocytic leukemia (CLL), 23 cases of acute myeloid leukemia (M1-M7), 5 cases of chronic myelocytic leukemia in blast crisis (CML-BC) and 2 mixed leukemias. In almost all of the cases examined, after TPA exposure cells from patients with proven myeloid leukemia became adherent to the substrate, while lymphoid leukemia cells remained in suspension, allowing the differentiation of lymphoid from myeloid blasts. The only exception was in one case of CLL, which had cells that became adherent with long filamental projections. In addition, increased phagocytosis following TPA exposure permitted characterization of M7 as this was the only myeloid leukemia negative for phagocytosis. Further discrimination between the subtypes of myeloid leukemia could be based on the increased lysozyme production seen after TPA in M4 and M5. Esterase positivity allowed the discrimination of M1 cells, which were negative before and after TPA treatment. In agreement with the results of other authors, TPA and RA led to independent ways of differentiation, granulocytic-like lineage and monocytic-like cells being favored by RA and TPA, respectively. The capacity of the same cell to differentiate into more than one lineage, depending on whether RA or TPA was used, was only seen in the present study with M3 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231181 TI - Optimal conditions for protease use in the assay of serum mitochondrial aspartate aminotransferase. AB - The optimal conditions for selective proteolytic inactivation of cytosolic aspartate aminotransferase (c-AST) to determine mitochondrial aspartate aminotransferase (m-AST) in serum were studied. Protease 401 was found to be effective over a pH range of 6.0-10.0. A pH of 9.5 with 0.5% albumin in the reagent mixture was determined to be optimal for inactivation of c-AST and preservation of m-AST, lactic dehydrogenase (LDH), and malic dehydrogenase (MDH) in the assay procedure. The presence of serum endogenous protein inhibitors such as alpha 1-antitrypsin and alpha 2-macroglobin did not inhibit protease 401. PMID- 2231182 TI - Novel and sensitive enzyme immunoassay (immune-complex-transfer enzyme immunoassay) for antihuman T cell leukemia virus type 1 IgG in human serum using recombinant gag-env hybrid protein as antigen. AB - A novel and sensitive enzyme immunoassay (immune-complex-transfer enzyme immunoassay) for antihuman T cell leukemia virus type 1 IgG (anti-HTLV-1 IgG) in human serum using recombinant gag(14-139)-env-(197-295) hybrid protein is described. Anti-HTLV-1 IgG in test serum was reacted with dinitrophenyl biotinyl bovine serum albumin-recombinant gag-env hybrid protein conjugate. The complex formed was trapped onto polystyrene balls coated with affinity-purified antidinitrophenyl group IgG. After washing to eliminate nonspecific IgG in the test serum, the complex was eluted from the polystyrene balls with dinitrophenyl L-lysine and transferred to polystyrene balls coated with streptavidin. After washing, anti-HTLV-1 IgG in the complex trapped onto the streptavidin-coated polystyrene balls was reacted with antihuman IgG gamma-chain Fab'-peroxidase conjugate. Peroxidase activity bound to the streptavidin-coated polystyrene balls was assayed by fluorometry. By transfer of the complex, the nonspecific binding of nonspecific human IgG was considerably reduced, and the detection limit of anti-HTLV-1 IgG in serum was lowered 30-300-fold compared with that by Western blotting, gelatin particle agglutination, and the conventional enzyme immunoassay, in which a recombinant gag-env hybrid protein-coated polystyrene ball was incubated with test serum and, after washing, with antihuman IgG gamma chain Fab'-peroxidase conjugate. Usefulness of the immune-complex-transfer enzyme immunoassay was demonstrated using 271 serum samples. PMID- 2231183 TI - Evaluation of the stick enzyme immunoassay in Caranx sp. and Seriola dumerili associated with ciguatera. AB - The stick enzyme immunoassay (S-EIA) using monoclonal antibody to ciguatoxin (MAb CTX) was used to examine clinically implicated fish and to pre-screen two species of fish, Caranx sp. (ulua or jack) and Seriola dumerili (kahala or amberjack), supplied by sports fishermen. All of the clinically implicated fish from the Department of Health gave S-EIA values greater than or equal to 1.3. The Caranx sp. and Seriola dumerili considered safe (less than or equal to 1.2 value) and consumed after testing gave no false-negative results. The S-EIA procedure using MAb-CTX proved to be specific, sensitive, and simple to use in the laboratory. It also proved to be useful in screening two large carnivorous fish for ciguatoxin and related polyethers prior to consumption. PMID- 2231184 TI - Alloalbumin in cerebrospinal fluid: report of a case and remarks on physiopathology. AB - Alloalbumin Tagliacozzo (313 Lys------Asn) was detected in the cerebrospinal fluid of a 27-yr-old woman. We studied this rare finding by means of high resolution electrophoresis, isoelectric focusing, and immunofixation. We herein discuss the importance of molecular mass versus superficial electrical charge in the transfer of plasma proteins through the blood-brain barrier. PMID- 2231185 TI - Effect of azidothymidine on soluble CD4 levels in patients with AIDS or AIDS related complex. AB - Circulating soluble CD4 (sCD4) levels were measured in 20 patients (11 with the acquired immunodeficiency syndrome [AIDS] and 9 with AIDS-related complex [ARC]) treated with azidothymidine (AZT) and in 12 patients (nine with AIDS and three with ARC) who were in the placebo group. The mean CD4 level in the AZT treatment group at baseline was 41 +/- 12 (SEM) U/ml. After 4 wk of treatment, the mean level decreased to 23 +/- 5; it was 29 +/- 10, 31 +/- 14, and 21 +/- 5 at 8, 12, and 16 wk of therapy, respectively. No significant changes were observed in the placebo group. These results suggest that AZT administration may be associated with reduced sCD4 levels in these patients. PMID- 2231186 TI - Clonal dermatoses: a conceptual and diagnostic dilemma. PMID- 2231187 TI - Detection of endothelin immunoreactivity and mRNA in pulmonary tumours. AB - Paraffin sections of 66 surgically resected lung tumours were immunostained with antisera to human endothelin-1 and to the C-terminal peptide of big endothelin. With both antisera, strong immunoreactivity was demonstrated in 11 of 15 squamous cell carcinomas and 11 of 16 adenocarcinomas. Focal immunoreactivity was seen in small cell carcinoma (2/12), large cell carcinoma (2/5), and carcinoid tumours (2/11). Four lymphomas and three sarcomas did not show endothelin immunoreactivity. Cryostat sections of 22 of the 66 tumours were hybridized with radiolabelled complementary RNA probes prepared from the 3' non-coding region of endothelin-1 cDNA, and the chromosomal genes encoding endothelin-2 and -3. In situ hybridization demonstrated the presence of endothelin mRNAs in 4 of 7 squamous cell carcinomas and in 5 of 8 adenocarcinomas, in a pattern similar to that shown by immunocytochemistry. No hybridization signals were obtained from the other types of tumours. In lung tissue adjacent to the tumours, endothelin like immunoreactivity and mRNA were detected in pulmonary endocrine cells and, in some cases, other epithelial cells, and in alveolar capillary endothelial cells. This study demonstrates the expression of endothelin in a number of pulmonary tumours and suggests a possible role for this peptide in the growth and/or differentiation of these tumours. PMID- 2231188 TI - The expression of Lewis(a) and Lewis(b) antigens reflects changes in fucosylation between normal and neoplastic cervical squamous epithelium. AB - Antibodies against the carbohydrate antigens Lewisa (Lea) and Lewisb (Leb) allow further investigation into the changes in fucosylation of the glycocalyx occurring during the normal and neoplastic development of cervical squamous epithelium. Lea and Leb are expressed on a broad zone of suprabasal cells in normal cervical squamous mucosa often independent of individual Lewis gene and secretor status. A proportion of Lea is expressed in sialylated form. In cervical intraepithelial neoplasia, the progressive dedifferentiation of the squamous mucosa is mirrored by loss of both Lea and Leb expression. In invasive squamous carcinomas, Lea and Leb expression is seen only on cells in areas of differentiation. The expression of Lea and Leb in normal and neoplastic cervical squamous epithelium resembles that of the Lex antigen described by us previously. The structural similarity between these antigens is highlighted and evidence for a common functional role in maintaining the integrity of squamous mucosae is discussed. PMID- 2231189 TI - Alpha-smooth muscle actin as a marker for soft tissue tumours: a comparison with desmin. AB - The immunoreactivity of a range of vascular and non-vascular smooth muscle tumours, rhabdomyosarcomas, and non-myoid lesions has been examined with the use of a monoclonal antibody to smooth muscle-specific actin and the muscle intermediate filament, desmin. In all cases of smooth muscle-derived tumours, the alpha-actin antibody yielded superior results. Staining of the myofibroblasts of fibromatoses was also seen. In contrast to desmin, immunoreactivity was not exhibited by rhabdomyosarcomas. We propose that this monoclonal antibody to alpha smooth muscle actin is a useful addition to the panel of reagents used for the characterization of soft tissue proliferations and tumours. The technical aspects of the application of this monoclonal antibody to immunohistochemistry are discussed. PMID- 2231190 TI - Bacillus Calmette-Guerin-treated superficial bladder cancer: correlation of morphology with immunophenotyping. AB - Thirty-five biopsies from 19 patients with superficial transitional cell carcinoma of the bladder, treated with intravesical bacillus Calmette-Guerin (BCG), were assessed histologically and immunohistochemically. Pretreatment biopsies were available for comparison in all cases and five cases of non specific cystitis were also examined. The inflammatory infiltrate was assessed with a streptavidin-biotin-peroxidase method using UCHL1, MT1, LN3, L26, HAM56, MAC387, Leu7 and anti-S100 in paraffin sections, and in 18 specimens were frozen tissues were available, Leu1, 2, 3, 4, 14, OKT10, HLA-DR and anti-Tac antibodies were applied. Post-treatment bladder biopsies showed severe oedema and a variable degree of inflammation. A granulomatous inflammation was seen in 11 cases, with granulomas present in six prostatic biopsies and acid-fast bacilli in two cases. The lymphoid infiltrate in all biopsies were largely T lymphocytes with a predominance of T helper cells present, often as a band-like infiltrate pressing against the residual epithelium, or the denuded bladder surface, and distributed in the vicinity of the granulomas. Activated lymphocytes were prominent in seven cases, although a moderate infiltrate of such cells was seen in all instances. Tac antigen was only occasionally expressed, and in a few NK cells were present among the infiltrates. In eight cases, HLA-DR was expressed in epithelial cells following BCG treatment, whereas all pre-treatment epithelial were negative. PMID- 2231191 TI - Silver stained nucleolar organizer region proteins (Ag-NORs) as a predictor of prognosis in colonic cancer. AB - Using a one-step silver nitrate staining technique, routinely processed tumour tissues of 49 carcinomas of the colon were investigated to demonstrate silver stained nucleoli (Ag-nus) and argyrophilic proteins associated with the so-called nucleolar organizer regions (Ag-NORs). Patients with attempted curative resections and tumour stages Dukes' A, B, C1 and C2, with an uneventful follow-up period of at least 48 months (N = 17), showed a statistically significant (P = 0.0001) lower mean number of scattered Ag-NORs (3.04; SD: 1.08) compared to patients who developed metastases during their follow-up period (N = 15; 5.40; SD: 1.28), as well as to patients who underwent palliative surgical treatment (N = 17; 4.48; SD: 1.67). Mean numbers of scattered Ag-NORs per nucleus and staging of the tumour were strongly related (P = 0.0001) to cancer-specific survival. The results indicate that the evaluation of silver-stained particles according to their different distribution patterns is of great value with regard to the clinical outcome of colonic carcinoma and may even allow a more accurate prognostic assessment of these patients than the WHO grading system, UICC staging system, the so-called Jass-scoring system, and Dukes' classification. PMID- 2231192 TI - Mutant p53--the commonest genetic abnormality in human cancer? PMID- 2231193 TI - DNA analysis by flow cytometry in malignant pleural mesothelioma: relationship to histology and survival. AB - In a retrospective study of 70 patients with malignant pleural mesothelioma, 168 formalin-fixed, paraffin-embedded tumour specimens were examined for DNA content by flow cytometry. In 20 patients where two or more blocks of the same tumour were available, there was considerable agreement between ploidy status and S phase percentage in the different specimens. There were no significant differences for survival for patients who had been exposed to asbestos and those in whom no exposure could be elicited, nor for aneuploid and diploid tumours. The S-phase content was examined for different areas of the same tumour and the percentages were largely in agreement. However, those patients who had tumours with an S-phase percentage greater than the median (6 per cent) had a significantly shorter survival than those with tumours of lower S-phase percentage. Differences in DNA content and other cell cycle parameters were not associated with the histological subtypes. PMID- 2231194 TI - A morphometrically-based classification rule for the diagnosis of primary mesothelial lesions. AB - A computer-aided morphometrical study was performed on histological specimens of reactive hyperplastic (n = 10) and malignant (n = 17) mesothelium. For each cell, seven nuclear features were measured and 13 parameters computed. Using stepwise variable selection, discriminant analysis chose the nuclear contour index, the standard deviation of the nuclear area, and the mean of the nuclear perimeter as discriminating features between hyperplastic and malignant mesothelium. The coefficients of these variables were included in a discriminant function which gave perfect discrimination between the two groups of lesions. When the function was assessed on a test set of hyperplastic (n = 10) and malignant (n = 17) mesothelial lesions treated as 'unknown', complete separation between these two diagnostic categories was achieved. This classification rule may help to increase the level of confidence with which a histological diagnosis of mesothelioma can be established. PMID- 2231195 TI - Histopathological changes in simian immunodeficiency virus infection. AB - The histological lesions were studied in seven rhesus and three cynomolgus monkeys infected with simian immunodeficiency virus for periods ranging from nine weeks to 18 months. Lymphoreticular changes included hyperplasia, follicular involution and depletion, and one animal had amyloidosis of the spleen. Hyperplastic changes also took place in mucosa-associated lymphoid tissue and infiltrations occurred in the vaginal mucosa of one animal, which could be significant in sexual transmission of the infection. The range of opportunistic infections was small compared with that in human AIDS patients, although two monkeys had Pneumocystis carinii pneumonia. Enterocolitis was a common finding and brown adipose tissue was transformed into a large vacuolated type. Lesions of the central nervous system were found in five of nine monkeys, and consisted of foci of glial activity and perivascular and meningeal lymphocytic infiltration. A lymphoma involving the lumbar spinal cord developed in one animal. PMID- 2231196 TI - Tracing disease genes through family studies. PMID- 2231198 TI - Culture, pain and cancer. PMID- 2231197 TI - Role of sinusoidal pressure in the development of vacuolation in liver cells. AB - Vacuolation of liver cells, which is often seen in patients with right-sided heart failure, is sometimes confused with fatty change, but the contents are components of blood. This study was undertaken using an isolated rat liver perfusion model to clarify the pathogenesis of vacuolation of liver cells. It has been demonstrated that (1) hypoxia alone cannot cause vacuolation; (2) elevation of the sinusoidal pressure leads to vacuoles in liver cells, irrespective of the oxygen content of the perfusate; and (3) the number and size of vacuoles are proportional to the height of the sinusoidal pressure, but not to the oxygen content of the perfusate. The reason why vacuolation generally appears in the pericentral area in patients with right-sided heart failure may be that the sinusoidal pressure in this area rises in parallel with the inferior vena cava pressure. PMID- 2231199 TI - Ectopic pregnancy in adolescents: a clinical review for pediatricians. AB - Pediatricians caring for sexually active female adolescents and young adults need to be aware of the history, symptoms, and signs of an ectopic pregnancy. A thorough history and physical examination, including the pelvic examination, as well as specific diagnostic tests such as repeated quantitative hCG measurements, and ultrasonography when indicated, are crucial to proper and early diagnosis of a nonruptured ectopic pregnancy manageable by laparoscopy. The key to early diagnosis is to include ectopic pregnancy in the differential diagnosis in any sexually active female patient who has abnormal vaginal bleeding or abdominal pain. With early diagnosis, close observation, and appropriate management, the outcome is more likely to be favorable, with minimal morbidity and risk of death. PMID- 2231200 TI - Very low birth weight children: behavior problems and school difficulty in a national sample. AB - We addressed three questions concerning the behavioral and academic status of low and very low birth weight infants through a secondary analysis of the 1981 National Health Interview Survey--Child Health Supplement: (1) in children born with very low birth weight, what is the risk of behavior problems and school difficulty compared with that in heavier low birth weight and normal birth weight children? (2) What are the correlates of school difficulty? (3) Are behavior problems associated with school difficulty when variables are controlled for these correlates? The analysis revealed that 34% of very low birth weight children could be characterized as having school difficulty, compared with 20% and 14% of the other groups, respectively, and that they were more likely to have higher scores on the hyperactive subscale of the Behavior Problems Index. Although a broad array of sociodemographic factors correlated with school difficulty, very low birth weight and hyperactivity scores contributed independently to the risk of academic problems. We conclude that very low birth weight infants are at risk of having school problems that are in part associated with hyperactive behavior. PMID- 2231201 TI - Serial magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy. AB - We prospectively performed magnetic resonance imaging (MRI) studies during the neonatal period, and at 4 and 8 months of age, on 15 term infants with hypoxic ischemic encephalopathy, and compared the results with their neurodevelopmental outcome at 18 months of age. Cerebral palsy developed in nine infants, two infants were classified as having abnormalities of tone and delayed motor milestones that were suggestive of cerebral palsy, and four infants were normal. Structural abnormalities, delayed myelination, or a combination of the two were detected with MRI at 8 months of age in all nine infants with later development of cerebral palsy. Three of the four normal infants and one infant with suggestive abnormalities had normal serial MRI findings. Each of the remaining two infants (one normal, one with suggestive abnormalities) had isolated persistent ventricular dilation on all three MRI studies. Our results suggest that 8 months appears to be the earliest time at which MRI findings correlate well with later adverse neurodevelopmental outcome in this population. PMID- 2231202 TI - Transient renal acidification defect during acute infantile diarrhea: the role of urinary sodium. AB - We studied urinary acidification daily during the hospital course of 16 infants with acute gastroenteritis and metabolic acidosis. Urine pH value on admission was higher than 5.5 in 14 (87%) patients. We hypothesized that inappropriate urinary acidification was due to sodium deficiency and inadequate sodium delivery to the distal nephron. Forty-one urinary samples were collected during metabolic acidosis. The mean pH of 24 urine samples with sodium concentration less than 10 mmol/L was significantly higher than the pH of 17 samples with sodium concentration greater than 10 mmol/L (6.04 +/- 0.06 vs 5.19 +/- 0.1; p less than 0.001). The urine ratios of titratable acid to creatinine and of total acidity to creatinine were significantly higher in urine samples containing more sodium (p less than 0.02), whereas the ammonium/creatinine ratio was not. After administration of furosemide or correction of the sodium deficit, appropriate acidification was observed. We conclude that impaired urinary acidification is frequently found during metabolic acidosis in infants with acute gastroenteritis and results from a sodium deficit rather than from transient distal renal tubular acidosis. PMID- 2231203 TI - Azathioprine and the treatment of chronic inflammatory bowel disease. PMID- 2231204 TI - Ruptured ectopic pregnancy complicating sexual abuse in an 11-year-old girl. PMID- 2231206 TI - Urolithiasis associated with the ketogenic diet. PMID- 2231205 TI - Advanced lung disease in a patient with cystic fibrosis and hypogammaglobulinemia: response to intravenous immune globulin therapy. PMID- 2231207 TI - Kasabach-Merritt syndrome: treatment with epsilon-aminocaproic acid and assessment by indium 111 platelet scintigraphy. PMID- 2231208 TI - Homozygous protein S deficiency in an infant with purpura fulminans. PMID- 2231209 TI - Association of Henoch-Schonlein purpura glomerulonephritis with C4B deficiency. PMID- 2231210 TI - Holoprosencephaly associated with diabetes insipidus and syndrome of inappropriate secretion of antidiuretic hormone. PMID- 2231211 TI - Arthrogryposis multiplex congenita with renal and hepatic abnormalities in a female infant. PMID- 2231212 TI - Prolonged indomethacin therapy for the prevention of recurrences of patent ductus arteriosus. AB - We tested the hypothesis that prolonged maintenance indomethacin therapy would allow more effective closure of patent ductus arteriosus (PDA) and thereby decrease the recurrence rate. Thirty-nine low birthweight neonates (less than 1500 gm) with confirmed PDA were randomly assigned in a double-blind fashion to receive standard indomethacin therapy (three doses), followed either by maintenance indomethacin therapy (0.2 mg/kg/day) for 5 days or by an equivalent volume of placebo for 5 days. Of the 20 infants who received maintenance indomethacin therapy, two (10%) required additional therapy and one of these required surgical ligation. Of the 19 infants who received only the first three indomethacin doses, nine (47%) required additional therapy for PDA (p less than 0.05) and seven of these had a ligation (p less than 0.05). We conclude that maintenance indomethacin therapy, in comparison with short-term indomethacin therapy, decreases the incidence of surgical PDA ligations, eliminates most PDA recurrences, and does not increase toxic effects of indomethacin in the low birth weight infant with PDA. PMID- 2231213 TI - Postexposure prophylaxis for measles in a neonatal intensive care unit. PMID- 2231214 TI - Renal blood flow velocity in preterm infants with severe respiratory distress syndrome. PMID- 2231216 TI - Azathioprine in the treatment of children with inflammatory bowel disease. AB - During a 6-year period, we treated 21 patients with azathioprine, 2 mg/kg/day, as an adjunct to their customary regimen. Nine patients had ulcerative colitis and 12 patients had Crohn disease; the patients' ages ranged from 3 to 17 years. The median duration of disease before the start of azathioprine therapy was 2 years, and median follow-up was 2 years. Sixteen patients seemed to respond to azathioprine therapy: six patients in each disease group had complete responses and four patients (one with ulcerative colitis and three with Crohn disease) had partial responses. Two patients with ulcerative colitis and three patients with Crohn disease did not respond. The median time until patients responded was less than 3 months for patients with ulcerative colitis and 4 months for those with Crohn disease. Reduction of corticosteroid dose was possible for all patients who responded to azathioprine therapy. Only minimal side effects were attributable to the drug. We conclude that azathioprine is an effective adjunctive agent for the treatment of inflammatory bowel disease in childhood, but because questions remain regarding its long-term safety, its use should be reserved for children with refractory disease or severe and unacceptable side effects of corticosteroids. PMID- 2231215 TI - Early ribavirin treatment of respiratory syncytial viral infection in high-risk children. AB - A 3-year prospective, blinded, multicenter study was done to assess the efficacy of early ribavirin intervention in mild respiratory syncytial virus illness in children with bronchopulmonary dysplasia or with congenital heart disease. A cohort of 178 children younger than 36 months of age with bronchopulmonary dysplasia or congenital heart disease were followed. Forty-seven infants whose respiratory syncytial virus infection resulted in mild symptoms of less than or equal to 72 hours' duration received ribavirin (n = 20) or water placebo aerosol (n = 27) either in a hospital or at home. Outcome measures included respiratory and analog score, room air oxygen, saturation, and oxygen flow needed to maintain saturation at greater than or equal to 91%. No difference in age, gender, family size, passive smoking, baseline oxygen saturations in room air, or duration of symptoms before treatment was found between groups. After 3 days of therapy, ribavirin produced a greater rate of improvement of analog scores (p = less than or equal to 0.001), lower oxygen requirements (p = 0.01), and higher oxygen saturation (p = 0.01). Respiratory scores and total hospital days did not differ significantly between the groups. Treatment failure occurred in 2 of 20 children (10%) in the ribavirin group versus 5 of 27 children (18%) in the placebo group, a nonsignificant difference. No child required assisted ventilation or had an adverse reaction. We conclude that early ribavirin therapy may help to reduce morbidity from respiratory syncytial virus infection in high-risk young children. PMID- 2231217 TI - Effects of cisapride in patients with cystic fibrosis and distal intestinal obstruction syndrome. AB - In a double-blind, placebo-controlled, crossover trial, we investigated the effects of the prokinetic drug cisapride in patients with cystic fibrosis and chronic recurrent distal intestinal obstruction syndrome (DIOS). After a baseline period, 17 patients (12.9 to 34.9 years; 12 boys) received, in random order, cisapride (7.5 to 10 mg) and placebo three times daily by mouth, each for 6 months. Gastrointestinal symptoms (flatulence, abdominal pain, fullness, abdominal distension, nausea, anorexia, heartburn, diarrhea, vomiting and regurgitation) were scored three times monthly and physical examinations assessed. At baseline and at each 6-month period, assessment included food intake for 7 days, 3-day stool collection, pulmonary function tests, and abdominal radiographs. During cisapride therapy compared with placebo, there were significant reductions in flatulence (p less than 0.005), fullness, and nausea (p less than 0.05). Patients with the worst symptom scores benefited most from cisapride. With cisapride, 12 patients felt better and three worse (p less than 0.05); physicians judged 11 patients improved and two worse (p less than 0.05). No side effects were noted. There were no significant differences between cisapride and placebo periods in nutritional status, x-ray scores, pulmonary function, food intake (fat, protein, calories), stool size and consistency, and fecal losses of fat, bile acids, chymotrypsin, and calories. For acute episodes of DIOS, intestinal lavage was needed 6 times in 4 patients during treatment with cisapride, and 11 times in 6 patients receiving placebo. In comparison with unselected patients with cystic fibrosis and pancreatic insufficiency who were receiving enzyme supplements and who had no distal intestinal obstruction, fecal fat losses (percentage of intake) were almost twice as high in the study group with DIOS (31.2 +/- 20.6% vs 16.2 +/- 17.6%; p less than 0.01). We conclude that in the dosage used, long-term treatment with cisapride appears to improve chronic abdominal symptoms in patients with cystic fibrosis and DIOS, but fails to abolish the need for intestinal lavage. Cisapride treatment had no effect on digestion and nutritional status of cystic fibrosis patients with pancreatic insufficiency. PMID- 2231219 TI - Fungal peritonitis in children on peritoneal dialysis. PMID- 2231218 TI - Interaction between trimethoprim-sulfamethoxazole and methotrexate in children with leukemia. AB - Because trimethoprim-sulfamethoxazole (TMP-SMX) causes neutropenia in children with leukemia, we investigated the possibility that pharmacokinetic interaction between methotrexate (MTX) and TMP-SMX causes accumulation of the antileukemia agent. We studied the pharmacokinetics of MTX given intravenously or orally to nine children with acute lymphoblastic leukemia, once with and once without TMP SMX. There was an increase in free MTX fraction during TMP-SMX therapy in all patients, from (mean +/- SD) 37.4 +/- 11% without TMP-SMX to 52.2 +/- 6.4% with TMP-SMX (p less than 0.01). Plasma clearance of total MTX did not change significantly, whereas clearance of free MTX decreased significantly (from 12.5 +/- 4 to 7.6 +/- 1.5 ml/kg/min; p less than 0.05). There was a consistent decrease in the renal clearance of free MTX (from 12.1 +/- 6.8 to 5.6 +/- 2.4 ml/kg/min; p less than 0.05). Elimination half-life of MTX was not affected significantly by TMP-SMX. There was a significant correlation between serum concentrations of TMP-SMX and the percentage of decrease in the renal clearance of free MTX (r = 0.91; p less than 0.05). These changes in protein binding and tubular clearance of MTX, caused by competition with TMP-SMX, result in a mean 66% increase in systemic exposure to MTX and may explain the myelotoxicity often observed with the coadministration of the two drugs. PMID- 2231220 TI - Neonatal necrotizing enterocolitis: bridging the basic science with the clinical disease. PMID- 2231221 TI - Convulsions in children with ventriculoperitoneal shunts. PMID- 2231222 TI - Metoclopramide for gastroesophageal reflux in infants. PMID- 2231223 TI - Urodynamics and hypercalciuria. PMID- 2231224 TI - Uridine diphosphate glucose and uridine diphosphate galactose in galactosemia. PMID- 2231225 TI - Prevention of rheumatic fever. PMID- 2231226 TI - The fetus as a patient. Sixth International Symposium. Detroit, Michigan, USA, October 25-27, 1990. Abstracts. PMID- 2231227 TI - Antibodies directed to the chemotactic factor receptor detect differences between chemotactically normal and defective neutrophils from LJP patients. AB - Localized juvenile periodontitis (LJP) is a progressively destructive infection of the supporting tissues of the teeth, primarily affecting adolescents. In this disease, patients' polymorphonuclear leukocytes (PMN) exhibit decreased chemotaxis (CTX) and decreased binding of the chemotactic peptide N-formyl-l methionyl-l-leucyl-l-phenyl-alanine (FMLP) to specific receptors on the PMN surface. Since the FMLP receptor is involved in the activation of the PMN, and its subsequent response to chemotactic stimuli, a decrease in the chemotactic peptide receptor, as seen in LJP patients, is suspected to be a predisposing factor for this disease. To define differences in the FMLP receptor between CTX defective LJP patients and CTX normal donors, a battery of monoclonal antibodies reactive against the FMLP receptor was prepared. The FMLP receptor was affinity purified, and was found to be comprised of two components, one of 68 kDa, and the other of 94 kDa. Only the 68 kDa component specifically bound a radioiodinated FMLP analogue in a photoaffinity experiment. Seven monoclonal antibodies were selected on the basis of their reactivity with the 68 kDa receptor component, and of these, 5 showed reduced binding against PMN from CTX defective LJP donors when compared to their reactivity against PMN from CTX normal subjects. Two of the 7 anti-68 kDa antibodies reacted with PMN from both sets of subjects at a comparable extent. Furthermore, the presence of 20 nmol of FMLP inhibited the binding of 5 of the anti-receptor antibodies to whole PMN, including one that showed no difference in binding between CTX normal and defective PMN, and 4 of the 5 that did show such difference.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231228 TI - Periodontal disease morbidity quantification. I. Optimal selection of teeth for periodontal bone loss surveys. AB - The assessment of alveolar bone loss with bite-wing radiographs is attractive because bite wings are relatively convenient, inexpensive, and available. The choice of teeth used influences the validity of global bone loss assessments based on partial mouth measurements. The objective of this study was to validate periodontal bone loss indices based on a few teeth. The mandibular posterior teeth were considered as a basis for abbreviated indices. The optimum number of teeth included was evaluated, and the utility of abbreviated indices was determined experimentally. The teeth from 75 skulls were measured from the cemento-enamel junction (CEJ) to the alveolar bone at six locations per tooth. The subsets of teeth which best represent the average whole mouth bone loss were found with all-possible-subsets regression analysis. Bone loss data from 179 prehistoric skulls were used to test the validity of selected teeth indices. Bone loss measurements from the mandibular posterior areas were representative of full mouth bone loss measurements. Mandibular second premolars plus any other mandibular posterior teeth were the optimal combination of tooth for an abbreviated index. This subset is suitable for use with bite-wing radiographs. PMID- 2231229 TI - Periodontal disease morbidity quantification. II. Validation of alveolar bone loss measurements and vertical defect diagnosis from digital bite-wing images. AB - Quantitative alveolar bone loss evaluation by digital processing of dental radiographs was performed. More than 20 contrast and edge enhancement techniques were applied to bite-wing radiographs of adult molar teeth and the results subjectively evaluated. Wallis space variant image enhancement was selected as the most promising candidate for improved visualization of the cemento-enamel junctions and alveolar crests. Seventy-three skulls were radiographed, the films digitized, and enhancement performed on the digital images. Alveolar bone loss measurements from skulls (truth) were compared with those from the original radiographs, unprocessed digital images, and enhanced digital images. The average intraclass correlation coefficient for two observers was 0.83 for radiographs, 0.86 for digital images, and 0.91 for enhanced images. The intraclass correlation coefficient between the 2 sets of dry skull measurements made by two additional observers was 0.88. Means and 95% confidence limits were determined for differences between measurements from dry skulls and radiograph-based images. In the worst case for measurements from enhanced images, the mean difference from truth was -0.40 mm with a 95% confidence interval from -0.54 to -0.25 mm. Receiver operating characteristic (ROC) analysis was used to determine the utility of radiograph-based images for the diagnosis of vertical defects. The ability of two observers to diagnose vertical defects on dry skulls was also tested. All methods of vertical defect diagnosis, including the identification of vertical defects on dry skulls, had relatively low diagnostic performance. Image processing technology has considerable potential in periodontal disease studies for quantitative evaluations of alveolar bone height. The diagnosis of vertical defects using current definitions and techniques is problematic, with considerable room for improvement. PMID- 2231230 TI - HTR polymer grafts in human periodontal osseous defects. I. 6-month clinical results. AB - HTR polymer was evaluated as a grafting material in periodontal osseous defects in 21 adult patients. Following initial preparation and pre-surgical documentation with standardized measurements, radiographs, and photographs, vertical osseous defects were treated with surgical open flap debridement alone (DEBR) or with DEBR plus placement of HTR polymer graft material. Patients were followed with frequent recalls until surgical re-entry at about 6 months for documentation and any needed remedial therapy. Re-entry data show that use of HTR polymer grafts resulted in significantly better mean defect fill of 2.2 mm (60.8%) compared to 1.0 mm (32.2%) with DEBR alone (P less than .001). Other hard tissue findings such as residual defect depth, crestal resorption, and percent defect resolution showed similar clinically superior results with the use of HTR polymer. Soft tissue findings showed significant differences in favor of HTR for decrease in probing depth and gain in clinical attachment. These results are similar to those reported with other graft materials. Over a 6-month period, HTR polymer was found to show promise for the repair of periodontal osseous defects. PMID- 2231231 TI - Actinobacillus actinomycetemcomitans in families afflicted with periodontitis. AB - The purpose of this study was to determine the prevalence of Actinobacillus actinomycetemcomitans (Aa) in individuals from families where at least one individual has an early onset form of periodontitis. Twenty-three families with 73 subjects were evaluated in this study. Forty-seven early onset periodontitis subjects outside the 23 families were also studied. Prevalence of detection of Aa in family members ranged from 49% to 66% among groups constituted by clinical findings indicative of no loss of attachment, adult periodontitis, generalized severe juvenile periodontitis, or localized juvenile periodontitis. Whether the data were analyzed by subject or by site, no statistical differences could be found in prevalence (proportion of positive samples) among those clinical groups. The only significant difference was that localized juvenile periodontitis subjects had higher concentrations of Aa in their Aa-positive sites than did the other clinical groups. The prevalence of Aa-positive sites in subjects without attachment loss, but who are members of families in which early onset periodontitis is represented, was much higher than in other reports where periodontally healthy subjects were not related to early onset periodontitis cases. This suggests that Aa may be transmitted among members of families in which one or more members has an early onset form of periodontitis. PMID- 2231232 TI - Peripheral ameloblastoma of the gingiva. A case report. AB - Reports of gingival peripheral ameloblastoma are extremely rare and have been sporadic. This paper reports a pertinent case of a 40-year-old woman who for 2 years had a progressively enlarging asymptomatic firm mass in the buccal gingival region of the lower premolars. Cupping of the underlying bone was radiographically demonstrated. The lesion was excised surgically together with extraction of the first premolar, and no evidence of recurrence was seen 5 years later. The clinical, radiological, and histopathological characteristics of gingival peripheral ameloblastoma were analyzed in the 33 previously reported cases. The differential diagnosis and treatment of this case report are discussed. PMID- 2231233 TI - Repair potential in localized juvenile periodontitis. A case in point. AB - An aggressive form of localized juvenile periodontitis (LJP) in a 12-year old West African female is reported. The case was treated with scaling, root planing, debridement, and tetracycline therapy, which resulted in complete resolution of the disease, including elimination of periodontal inflammation, regeneration of lost periodontal structures, and spontaneous repositioning of teeth that had pathologically migrated. A hopelessly involved mandibular right first molar was successfully replaced by an incompletely developed maxillary third molar tooth bud whose roots and pulp structure continued to develop after autotransplantation. It is suggested, that LJP can be successfully treated without periodontal surgery and that the potential for repair in LJP cases is apparently greater than what one can anticipate in adult forms of periodontitis. PMID- 2231234 TI - Stability of MMPI scale scores within four codetypes across forty years. AB - The changes in the standard validity and clinical scales on the Minnesota Multiphasic Personality Inventory (MMPI) were examined within four frequently occurring codetypes (Spike 4, 2-4/4-2, 2-7/7-2, and 6-8/8-6) in samples of psychiatric patients over a time span of 40 years. The validity and clinical scale scores within these four codetypes were very stable over this time span with differences in the range of only a few T-score points. These results are very similar to those reported by Pancoast and Archer (1989) who found remarkable stability in the MMPI scale scores of normal adult samples across 40 years. PMID- 2231235 TI - The Levels of Emotional Awareness Scale: a cognitive-developmental measure of emotion. AB - The Levels of Emotional Awareness Scale (LEAS) is based on a new cognitive developmental model of emotional experience. The scale poses evocative interpersonal situations and elicits descriptions of the emotional responses of self and others which are scored using specific structural criteria. Forty undergraduates (20 of each sex) were tested. Interrater reliability and intratest homogeneity of the LEAS were strong. The LEAS was significantly correlated with two measures of maturity: the Washington University Sentence Completion Test (SCT) of Ego Development, and the Parental Descriptions Scale-a cognitive developmental measure of object representation. In addition, the LEAS correlated positively with openness to experience and emotional range but not with measures of specific emotions, repression or the number of words used in the LEAS responses. These findings suggest that it is the level of emotion, not the specific quality of emotion, that is tapped by the LEAS. PMID- 2231236 TI - Attitudinal body-image assessment: factor analysis of the Body-Self Relations Questionnaire. AB - This article presents an analysis of the factor structure of the Body-Self Relations Questionnaire (BSRQ), an attitudinal body-image instrument. Random stratified samples, drawn from a national survey, included 1,064 females and 988 males. In order to evaluate the replicability of the BSRQ factor structure, separate split-sample factor analyses (principal components with varimax rotation) were conducted for each sex. Largely consistent with the conceptual basis of the BSRQ, the resultant factors derived from each analysis were: Appearance Evaluation, Appearance Orientation, Fitness Evaluation, Fitness Orientation, Health Evaluation, Health Orientation, and Illness Orientation. Subsequent concordance analyses revealed marked stability of the factor structure both within and between sexes. Females demonstrated somewhat greater differentiation of body-image attitudes than did males. The utility of the BSRQ is discussed relative to extant body-image measures. PMID- 2231237 TI - Does test anxiety bias scholastic aptitude test performance by gender and sociocultural group? AB - This study examines the commonly held contention that test anxiety may serve as a source of bias in the scholastic aptitude test performance of gender and ethnic minority groups. In addition, this study examines sex and sociocultural group differences in the level and pattern of test anxiety among Israeli college students. The sample was composed of 163 male and 198 female students sitting for scholastic aptitude tests routinely administered to all student applicants as part of their college admissions procedures. About 67% were of Western cultural extraction whereas the remainder were of Eastern extraction. Significant differences in text anxiety scores for males and females were observed, with greater sex group differentiation on the Emotionality than on the Worry scale. Test anxiety scores were not discernible by ethnicity or social class. Furthermore, test anxiety was not differentially related to aptitude test scores by sex or sociocultural group membership. Thus, this study lends little evidence to the common contention that test anxiety differentially debilitates the aptitude test scores of females and ethnic minority student candidates. PMID- 2231238 TI - The measurement of principled morality by the Kohlberg Moral Dilemma Questionnaire. AB - The four stages preceding the postconventional level in the Kohlberg (1958, 1971, 1976) system of moral development are described as involving moral judgments that conform to external conditions of punishment, reward, social expectation, and conformity to the law. No special level of self-control seems necessary to behave in keeping with these conditions of external reinforcement. In contrast, the two stages of postconventional (principled) mortality involve defiance of majority opinion and defiance of the law--actions that would seem to require greater self control. This study was concerned with whether postconventional moral reasoning, as measured by the Kohlberg Moral Dilemma Questionnaire (MDQ), can be associated with higher self-control. If so, prediction of principled moral behavior from the MDQ would be based not only on postconventional moral reasoning but bolstered by the necessary level of self-control as well. College students who came the closest to postconventional moral reasoning showed better self-control than college students who were more conventional or preconventional in their moral judgments. These results support the validity of the MDQ for predicting principled moral behavior. PMID- 2231239 TI - Estimation of MCMI DSM-III axis II constructs from MMPI scales and subscales. AB - Wiggins, Harris and Lingoes, and Serkownek Minnesota Multiphasic Personality Inventory (MMPI) scores were used to predict Millon Clinical Multiaxial Inventory (MCMI) scores in a 100-patient sample. Equations from the first sample were cross validated on a sample of 212 inmate subjects. We conclude that scores on 19 of the 20 MCMI scales can be successfully predicted by the Wiggins, Harris and Lingoes, and Serkownek subscales of the MMPI. In further cross-validation, the equations were used to predict the Morey, Waugh, and Blashfield MMPI composites for the prison sample, again with strongly positive results. The results appear quite promising for the estimation of personality disorder constructs from MMPI scales and subscales. PMID- 2231240 TI - Retest reliability of the Millon Clinical Multiaxial Inventory. AB - This article reports on two studies which examined the temporal stability of the personality disorder subscales from the Millon Clinical Multiaxial Inventory (MCMI). The scales demonstrated adequate stability in psychiatric inpatients (retested with an average of just over 1 year between testings). Furthermore, a separate sample of depressed inpatients assessed when depressed and 6 weeks later showed that the stability of MCMI personality scales was observed even after patients displayed an initial reduction in depression severity. Although stability is vital to the accurate assessment of personality disorders, both studies also found high retest correlations for the MCMI clinical syndrome subscales. In general, these results suggest that patients displayed similar symptom patterns over time, whether construed as personality traits or characteristic patterns of responding when symptomatic. PMID- 2231241 TI - Stability of the MCMI among depressed psychiatric outpatients. AB - The Millon Clinical Multiaxial Inventory (MCMI) is a promising, yet somewhat unproven psychometric inventory developed to identify clinical syndromes and personality traits consonant with the Diagnostic and Statistical Manual of Mental Disorders (3rd ed. [DSM-III]; American Psychiatric Association, 1980). The stability of its measures for both the theoretically more stable personality characteristics and the clinical syndromes was investigated in a group of depressed psychiatric outpatients. In this test-retest design with a 3-month interval between tests, clinical syndrome scales of relevance changed significantly as expected. However, many of the personality scales also changed significantly. Only four of the personality scales met a two-fold test of stability. Findings are discussed in terms of characteristics of self-report inventories such as the MCMI, the uniqueness of the depressed population, and characteristics of personality disorders. PMID- 2231242 TI - MCMI-II scoring: weighted and unweighted algorithms. AB - This brief report examines the relationship between the scale scores derived through weighted and unweighted item scoring on the Millon Clinical Multiaxial Inventory-II (MCMI-II). The inventories of 356 subjects across three samples were scored using weighted and unweighted algorithms. Correlations between the weighted and unweighted MCMI-II scales were found to approach unity. This casts doubt on whether the weighting system has substantial effect on the profiles that are generated or on reducing interscale correlations. PMID- 2231243 TI - The Beck Depression Inventory: item order and the impact of response sets. AB - The lack of subtle content in the item groups of the Beck Depression Inventory (BDI) and the consistency in the ordering of the items from least to most pathological make this instrument unduly susceptible to either defensive or malingering response sets. Two experimental forms were developed for the BDI: a backwards version (a simple reversal of the order of items within each group) and a random-order version. These forms, together with the original item order, were given to college undergraduate women along with the Depression scale from the MMPI and the Burks-Martin Questionnaire covering recent life changes and current stressful situations. The random order BDI results in a significantly higher depression score than did either the original or backwards version. Correlations with the other instruments were comparable for all three forms. The random order of items within each set appears to break up a response set to endorse either the first or last item and is, therefore, recommended. PMID- 2231245 TI - Gender differences in depression in an employment setting. AB - This study extends the literature on sex differences in depression to an employment setting, using Minnesota Multiphasic Personality Inventory (MMPI; T and raw scores) and Depression (D) 30 measures. In contrast to previous findings, no gender differences remained on any of the measures after the effects of salary, age, education, and job classification had been taken into account. Findings replicated earlier results showing depressed males to have greater difficulty with concentration and motivation than depressed females. Data suggest that MMPI sex-based T-scores may overcorrect for sex differences in raw scores. Possible explanations for the findings are discussed, including a general improvement in women's well-being associated with changes in social conditions such as employment, or the possibility of a self-selection bias in our sample. PMID- 2231244 TI - Multimethod assessment of depression in sexually abused girls. AB - This study measured depression in sexually abused Black girls using the Children's Depression Inventory (Kovacs & A. T. Beck, 1977), the Internalization scale of the Child Behavior Checklist (Achenbach & Edelbrock, 1983), and the Rorschach Depression Index (Exner, 1986). There were no significant correlations between these self-report, behavior observation (by parental report), and projective measures. The abused subjects had high scores on the behavior observation and Rorschach scales. Consistent with past research, negative results were obtained with the self-report instrument. We suggest that the low scores on self-report measures of distress produced by sexually abused children may be the result of guardedness or defensiveness rather than a genuinely low level of dysphoria in this population. There were no significant relations between abuse characteristics and scores on the depression measures. Scores on Rorschach measures of organizational activity (Zf) and available coping resources (EA) were generally positively related to depression within the abuse group and negatively related to depression within the control group. PMID- 2231246 TI - Contingent reinforcement effects on movement responses of prison inmates to the Holtzman Inkblot Technique. AB - Prison inmates were administered the Holtzman Inkblot Technique (HIT) under conditions of either verbal or nonverbal reinforcement of movement responses. Overall, there were no differences among the verbal, nonverbal, and control groups. Inmates charged with violent crimes were found to give the fewest movement responses. With crime category controlled, more movement responses were given under nonverbal conditions. There were no sex differences for movement responses but testing time increased significantly when administered by the female examiner. PMID- 2231247 TI - A Rorschach investigation of narcissism and hysteria in antisocial personality. AB - We investigated Rorschach responses associated with narcissism and hysteria in a group of antisocial personality disordered offenders. The Rorschach protocols of 42 subjects who met the criteria from the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-III-R]; American Psychiatric Association, 1987) for antisocial personality disorder were analyzed using Exner's (1986) criteria for pairs, reflections, and personal responses, and Gacono's (1988) criteria for the impressionistic response. Severe, or primary psychopaths (n = 21), scoring greater than or equal to 30 on the Hare (1980) Psychopathy Checklist (PCL), were compared to moderate, or secondary pscyhopaths (n = 21), scoring less than 30 on the PCL. The mean number of pair and impressionistic responses did not significantly differ for the two antisocial groups. The highly psychopathic group, however, did exhibit a significantly greater mean number of reflection and personal responses. We discuss pair and reflection responses and their relationship to narcissism in psychopathic disturbance. We recommend interpreting the personal response within the context of the psychopathic character and view personal responses as expressions of narcissism and omnipotence in highly psychopathic subjects. We also hypothesize that the impressionistic responses are indicative of primitive dissociative processes and hysteria in psychopathic subjects, and that their presence provides construct validity for the work of Guze (1976) and others who suggested an underlying histrionic dimension to psychopathy. PMID- 2231249 TI - Severe disturbance or trauma-induced adaptive reaction: a Rorschach child case study. AB - In interpreting children's Rorschachs, it is often difficult to discriminate between a severe disturbance and an adaptive reaction to a trauma. To explore this difficult differential diagnostic issue, a child was tested three times. It was suggested that complexity, references to the trauma, and evidence of psychological disturbance are associated with an attempt to master the trauma. Rorschach data were presented and were found to be consistent with these speculations. The author concluded that such "openness" to an environmental stress may allow an adaptive reaction and that understanding Rorschach data in context helps to reduce ambiguity and to recognize the test's limitations. PMID- 2231248 TI - Oral-dependence and gender: factors in help-seeking response set and self reported psychopathology in psychiatric inpatients. AB - Psychoanalytic theory suggests that orality and being female are positively related to adopting a help-seeking stance in the world. This may result in inflated scores on self-report psychological tests. These hypotheses were investigated using Rorschach-based, oral-dependence scores (Masling, 1986), the Minnesota Multiphasic Personality Inventory (MMPI) help-seeking F minus K index (Gough, 1950; Meehl, 1951), and the MMPI clinical and supplementary scales. High orals are found to be more likely than low orals to adopt a help-seeking response set which in turn results in inflated scores on a number of MMPI clinical scales. Contrary to stereotypes, women are no more likely than men to be help seeking or oral dependent. Several other significant findings, including that orality is positively related to MMPI Scale 2 (Depression) scores for women, not men, are also discussed. PMID- 2231250 TI - Object relations in borderlines, depressives, and normals: an examination of human responses on the Rorschach. AB - Recently, researchers and clinicians have become increasingly interested in diagnostic distinctions between borderline and mood disorders. Object relations theory provides a useful framework for the comparison of these two overlapping diagnostic categories. In our study, a measure of object relations as represented on the Rorschach, developed by Blatt, Brenneis, Schimeck, and Glick (1976), was applied to data produced by borderline and depressive inpatients and by normal comparison subjects. Portions of the Blatt measure that tap the subject's experience of human action and interaction distinguish among the three diagnostic groups. Specifically, borderlines tend to understand human action as more highly motivated and human interaction as more malevolent in nature than do either depressive or normals. The data indicate that borderlines experience the object relational world in a way that is fundamentally different from the way normals and depressives perceive it. Implications are discussed for theories of borderline object relations. PMID- 2231251 TI - Assessing object representations as a continuous variable: a modification of the concept of the object on the Rorschach scale. AB - Current methods for assessing the quality of internalized object representations have not provided a continuous variable that simultaneously includes both an accuracy and a maturity component. A modification of Blatt, Brooks, Brenneis, and Schimek's (1976) Concept of the Object on the Rorschach scale that would combine the two components by weighting the quality of each response according to its form level was proposed. Initial discriminant and convergent validity of this modification was checked through correlations and multiple regression analyses using behavioral, diagnostic, and demographic data from 84 adolescent inpatients as dependent variables. Results indicate the modified score was directly related to measures of peer relatedness, intelligence, psychological health, and reality testing, and indirectly related to measures of psychosis and hostile, unmanageable behavior. The results support the utility of the modification for providing a continuous score that assesses both developmental maturity and accuracy, the two dimensions on which the concept of object representation is based. PMID- 2231252 TI - Rorschach responses in healthy, community dwelling older adults. AB - Five predicted relationships between age and intellectual level and 16 Rorschach variables were examined through a cross-sectional analysis of 47 healthy, community-dwelling elderly men and women. Subjects were compared by age and intellectual level using gender, level of medication, and scores on the Geriatric Depression Scale (GDS) and the Geriatric Social Readjustment Questionnaire (GSRQ) as covariates. Screening tests for psychiatric and physical illness, recent life events, and hearing and vision loss were administered. In contrast to prior research suggesting changes in Rorschach scores with differences in age and intellectual level, only one significant difference was found for these variables. The data suggest that age and intellectual level may contribute less to Rorschach responses than was previously thought. PMID- 2231253 TI - Relationships between Hand Test variables and maladjustment in school children. AB - Twenty-two Hand Test variables significantly differentiated a group of children referred to school psychologists for social and emotional maladjustment from a control group matched on age and sex. Eleven variables emerged from a subsequent stepwise discriminant analysis, resulting in a 80.85% hit rate. Results are interpreted as providing statistical support for the use of the Hand Test as a screening and/or ancillary projective technique in assessing school children. PMID- 2231254 TI - Personality characteristics of eating-disordered outpatients as measured by the Hand Test. AB - The Hand Test was administered to 34 eating-disordered and 26 noneating disordered college-age women to determine discriminating projective personality features. Eating-disordered women scored higher on response time, overall pathology, and passivity. Anorexics present more tension, aggression, and acting out potential whereas bulimics demonstrate significantly more passive responses. The more severely affected women scored higher on crippled, passive, and withdrawal variables. Similarities as well as differences between the groups may have important implications for the diagnosis of subgroups of eating-disordered women and for treatment planning. PMID- 2231256 TI - Further evidence concerning motivational distortion on the Sixteen Personality Factor primaries by male felons. AB - A multiple regression analysis was used to determine the susceptibility of the 16 Personality Factor Test (16PF) to faking for a sample of male felons. The study is a replication of an earlier study of a similar sample. Motivational distortion (MD) correlated significantly with the 16PF primary scores. The relationship was most evident when the structure coefficients rather than the beta weights were analyzed. The findings were consistent with the previous results which indicated a fairly high degree of support for the MD corrections provided in the manual. An important exception was that Dominance (E) was suppressed by individuals from both samples when MD was present. PMID- 2231255 TI - Personality factors, family structure, and sex of drawn figure on the Draw-A Person Test. AB - One hundred seventy-four youthful psychiatric inpatients were given the Draw-A Person Test (DAP) as part of an assessment battery. Sex of person drawn was compared to subject's sex, Achenbach aggression and delinquency scores, and scores on Children's Inventory of Anger and Nowicki-Strickland Locus of Control Scale. The sex of the person drawn was also compared to family composition, specifically whether or not the child came from an intact family with both a male and female parent or role model. Results support drawing of a same-sexed individual as normative, regardless of age or sex. Adolescent girls and young boys were the only groups that differed significantly from this norm. Personality measures and family composition were not significantly related to the tendency to draw same versus opposite sex. PMID- 2231257 TI - Augmenting Hopkins SCL scales to measure dissociative symptoms: data from two nonclinical samples. AB - A 13-item Dissociation scale is introduced, and preliminary data regarding its reliability are presented. Designed to complement the Symptom Checklist (SCL-90; Derogatis, Lipman, & Covi, 1973) and the Hopkins Symptom Checklist (HSCL; Derogatis, Lipman, Rickels, Ulenhuth, & Covi, 1974), this scale may be especially useful in research on the effects of psychological trauma. PMID- 2231258 TI - Personality assessment training in counseling psychology programs. AB - Although data about personality assessment training in clinical psychology programs have often been gathered, little comparable data have been collected about assessment training in counseling psychology programs. To collect such information, we conducted a survey of all programs identified as part of the Council of Counseling Psychology Training Programs. A two-page questionnaire was sent out to the 64 program directors, with 56 (88%) of the questionnaires being returned. Information about availability of required personality assessment courses, availability of elective assessment courses, and types of personality tests covered in the counseling curriculum is presented and discussed. PMID- 2231259 TI - The Depressive Experiences Questionnaire: a critical review. AB - The Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976) is critically reviewed. First the developmental, object representations theory differentiating depression into anaclitic and introjective subtypes is presented. The DEQ factors of Dependency and Self-Criticism were initially found to be consistent with these clinically meaningful depressive subtypes. Subsequent research has generally demonstrated that these subtypes, at least as measured by the DEQ, do not hold up well in clinical populations. Furthermore, the validity of the developmental theory of these subtypes is weak. We suggest that more internally consistent and distinct factors should be developed from clinical populations because of their potential clinical usefulness. PMID- 2231260 TI - Psychometric properties of the Depressive Experiences Questionnaire in a college population. AB - The Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976) was developed to permit the study of the continuities between normal and pathological forms of depression. Since its publication over 10 years ago, the DEQ has been increasingly used in a wide range of investigations of depression in clinical and nonclinical samples and as a measure of two major personality dimensions in a number of studies of differential responsiveness to various life stressors. This study provides an analysis of the DEQ responses in a large sample of undergraduate subjects in an attempt to articulate more clearly the psychometric properties of the DEQ. The DEQ consists of 66 items describing experiences frequently reported by depressed individuals. In the original development of the DEQ, factor analyses using male and female undergraduate samples yielded three orthogonal factors, Dependency, Self-Criticism, and Efficacy (Blatt et al., 1976). Most subsequent studies have used the factor scoring coefficients from the female sample to score men and women's DEQs. The factor loadings in the new male and female samples were very similar to one another and to the original female factor loadings. Thus, the continued use of the scoring parameters from the original female sample is recommended. Factor scores for Dependency and Self-Criticism continue to be uncorrelated in both men and women. Normative data are presented from the new samples, with men scoring higher on Self-Criticism and women scoring higher on Dependency. PMID- 2231261 TI - External validity of the new Devereux Adolescent Behavior Rating scales. AB - The discriminant and concurrent validity of the five new scales for the Devereux Adolescent Behavior Rating Scale (DAB) was explored using a heterogeneous sample of psychiatric and substance abuse patients. Consistent with predictions, the substance abuse patients scored higher on the Acting Out Behaviors (AOB) and Heterosexual Interests (HI) scales, and psychiatric patients scored higher on the Psychotic Behaviors scale. Gender differences also were found, including boys being rated higher on Acting Out Behaviors, and girls higher on Heterosexual Interests. The new DAB scales demonstrated sufficient concurrent validity using a thorough record review and a patient rating scale (the Child Behavior Checklist [CBCL]). The Neurotic/Dependent Behaviors scale (NDB) showed a consistent relationship with substance abuse and several other measures of more externalizing behaviors, in addition to the predicted relationships with anxious, tense, and dependent behaviors. The Withdrawn/Timid Behaviors scale (WTB) proved to be a purer measure of internalizing behaviors in both sexes. PMID- 2231263 TI - Cognitive-perceptual theory and the projective use of autobiographical memory. AB - Most clinicians know little about the operation of autobiographical memory. Yet as assessment people, clinicians are frequently called upon to make important decisions about the individuals they evaluate. It is not surprising that clinicians are ignorant regarding many aspects of autobiographical memory because most have not been trained to understand how autobiographical memory functions. This article focuses on a vital domain of autobiographical memories--early memories--and discusses from a clinical perspective the purpose, function, and organization of autobiographical memory as seen by cognitive-perceptual theory. PMID- 2231262 TI - Item factor structure of the Personality Adjective Check List. AB - This study reports on a principal-components analysis of the Personality Adjective Check List (PACL) at the item level. Data came from a national sample of normal adults and included the responses of 1,058 men and 1,194 women (N = 2,252). Analyses were conducted separately for men and women, and for the sexes combined. The scree test was applied to decide on the number of factors to extract. Retained factors were rotated by varimax and direct oblimin procedures. Results were very similar for each analysis, with coefficients of congruence for the five orthogonal factors obtained from men and women separately being .95, .92, .94, .94, and .92. The five unipolar personality dimensions isolated were interpreted as Aggressive/Dominant, Neurotic, Conscientious, Detached/Introverted, and Surgent/Extraverted. These were compared to item factors of the Million Clinical Multiaxial Inventory (MCMI-I), MCMI-II, Adjective Check List (ACL), and to Norman's Big Five dimensions. PMID- 2231264 TI - Dose-dependent pharmacokinetics and first-pass metabolism of acetaminophen in rats. AB - In order to investigate the in vivo first-pass metabolism of acetaminophen (AAP) following the oral and intraduodenal administration in rats, a pharmacokinetic compartment model including absorption process was developed. Using the parameters for the disposition kinetics of AAP and its metabolites, sulfate and glucuronide, which were determined in the separate study, the extent of the first pass metabolism and the contribution of sulfation and glucuronidation to the total first-pass metabolism in vivo were quantitatively estimated. As for the results, the first-pass metabolism of AAP following the oral and intraduodenal administration was mainly attributable to the sulfo-conjugation pathway in rats. The sulfation of AAP in the intestine and/or in the liver during the first-pass was proved to be a saturable process. Then, the sulfation in the first-pass metabolism showed the dose- and absorption rate-dependent kinetics. Thus, the pharmacokinetic model including the absorption process proposed in the present study was proved to be valid and useful for the estimation of in vivo first-pass metabolism of AAP in rats. PMID- 2231265 TI - Inhibition of testosterone biosynthesis in testicular microsomes by various imidazole drugs. Comparative study with ketoconazole. AB - Ketoconazole (KCZ), an imidazole-containing antimycotic, has been demonstrated to inhibit testosterone biosynthesis in man. In this study, the inhibitory activities of various imidazole drugs such as miconazole (MCZ), cimetidine (CIM), ozagrel (OZA) and its metabolites (M-1 and M-2) on the pathway of testosterone biosynthesis in testicular microsomes were compared with that of KCZ in vitro. Additionally, the changes in serum testosterone level in the patients by the treatments with MCZ were followed. KCZ inhibited 17 alpha-hydroxylase and C17,20 lyase activities in a dose-dependent manner, while it did not affect 17 beta hydroxysteroid dehydrogenase activity. Although the patterns of the inhibitory actions and the interaction of either imidazole drugs with cytochrome P-450 as 17 alpha-hydroxylase and C17,20-lyase were similar to those of KCZ, the inhibitory potencies and affinities for the cytochrome P-450 system decreased in the order of KCZ greater than MCZ greater than OZA greater than M-2 greater than M-1 greater than CIM. At the end of the intravenous injection of 200 mg MCZ to the patients, the serum testosterone levels decreased by about 16% of the original level and then returned to the original level 5 h after the end of injection. These results indicate that either imidazole drugs tested could inhibit a cytochrome P-450 enzyme C17,20-lyase mainly in testicular microsomes, and suggest that MCZ, a potent inhibitor subsequent to KCZ, induces a slight alteration in the testosterone biosynthesis in its clinical use. PMID- 2231266 TI - In vivo and in vitro evidence for a common carrier mediated transport of choline and basic drugs through the blood-brain barrier. AB - The blood-brain barrier (BBB) transport system for choline and basic drugs was characterized by the in vivo carotid artery injection technique (Oldendorf, Brain Res., 24, 372-376, 1970) and in vitro uptake into isolated bovine brain capillaries (Pardridge et al., J. Neurochem., 44, 1178-1184, 1985). Basic drugs such as eperisone, thiamine and scopolamine significantly inhibited choline uptake by the BBB with the half inhibitory concentration, IC50 value of 1.45, 2.06, and 0.47 mM, respectively. On the contrary, the uptake of choline was not inhibited by amino acids (L-phenylalanine and L-arginine) and acidic drugs (nicotinic acid, salicylic acid and valproic acid). Choline was taken up by the isolated brain capillaries in concentration and temperature dependent manners. The uptake of choline by the isolated bovine brain capillaries was significantly inhibited by eperisone, scopolamine and thiamine in consistent with the in vivo results. Furthermore, eperisone inhibited competitively the uptake of choline with the inhibition constant, Ki value of 455 microM. According to these results it was suggested that in the BBB choline and basic drugs would share a common carrier-mediated transport system. PMID- 2231267 TI - Isolation of bacterial strains, which hydrolyze glycyrrhizin and produce glycyrrhezic acid, from soil. AB - We isolated eight bacterial strains which could hydrolyze glycyrrhizin to glycyrrhezic acid. The bacterial strains were identified as three strains of Pseudomonas saccharophila, two of Plesiomonas sp., one of Pseudomonas stutzeri, one of Klebsiella pneumoniae subsp. ozaenae and one of Kluyvera ascorbata. Their capacity for the conversion of glycyrrhizin to glycyrrhezic acid was assayed by high performance liquid chromatography. P. saccharophila 11 was the most effective among the eight strains. Then, beta-glucuronidase, which is responsible for hydrolysis of glycyrrhizin, activity was assayed with p-nitrophenyl-beta-D glucuronide as a substrate. P. saccharophila 11 showed the highest beta glucuronidase activity among the eight strains. This indicates that P. saccharophila 11 may be useful for production of glycyrrhezic acid from glycyrrhizin by industrial fermentation. PMID- 2231268 TI - Relation of disposition kinetics to pharmacological effect of intravenous administration of chlorzoxazone in rats. AB - The quantitative relationship between a drug disposition and the pharmacological effect was examined in rats using chlorzoxazone (CZX), a centrally acting muscle relaxant, as a model drug. After intravenous administration of CZX, the decay of the plasma concentration was rapid and it was found that CZX obeyed one compartment open model in the dose range of 5 to 25 mg/kg studied. The pharmacological response intensity was determined by means of the crossed extensor reflex. The duration of the muscle relaxant effect was proportional to the logarithm of the dose of CZX. The time course of the calculated plasma concentration was well related to the pharmacological response intensity via a Hill's equation and the simulated pharmacological response intensity which was obtained by means of the equation was coincident to the time course of the response data. These results indicated that the time course of pharmacological response intensity was able to be predicted using the time course of plasma concentrations. From the analysis of the quantitative relationship between the concentration and the effect under the present experimental conditions studied, it was found that the biophase compartment was identical to the central compartment as long as the first order processes were proceeding. These findings implied that the time course of pharmacological response would be quantitatively predictable from the disposition kinetics of CZX after the intravenous administration. PMID- 2231269 TI - Pharmacological studies of lappaconitine. Analgesia produced by intracerebroventricular, intracisternal and intrathecal injections. AB - The antinociceptive effects of lappaconitine (LA) and morphine (MOR) when injected intracerebroventricularly (i.c.v.), intracisternally (i.cist.) or intrathecally (i.t.) were investigated in mice by use of the tail pinch, hot plate and acetic acid-induced writhing tests. In addition, the effects of naloxone (NLX) administered subcutaneously on the antinociceptive action of LA and MOR were studied. LA and MOR after i.c.v., i.cist. and i.t. injection produced dose-dependent antinociception. MOR was more potent in the tail pinch and acetic acid-induced writhing tests by i.t. injection than by i.c.v. or i.cist. injection, but the potency in the hot plate test was independent of the injection site. On the other hand, like MOR, LA was more potent after i.t. injection than after i.c.v. or i.cist. injection in the tail pinch and acetic acid-induced writhing test. Its antinociceptive action was less potent than that of MOR. The antinociceptive actions of MOR were antagonized by NLX (1 mg/kg, s.c.) in every test and injection site, whereas the antinociceptive actions of LA were not inhibited, except for the antinociception on the tail pinch test, which was partially antagonized by NLX. It is suggested that LA mainly produced an NLX resistant antinociceptive effect at the spinal site. PMID- 2231270 TI - Light suppression of melatonin in the squirrel monkey (Saimiri sciureus). AB - This study examined plasma melatonin levels and the suppressant effect of light on melatonin production in the squirrel monkey. Monkeys were maintained on a 12:12 light-dark cycle (LD 12:12) with lights on from 07:00 to 19:00. Plasma levels of melatonin were determined by gas chromatography negative chemical ionization mass spectrometry. Melatonin levels at 00:00 (99.5 +/- 18.9 pg/ml) were significantly higher than at 02:00 (57.21 +/- 7.7 pg/ml; Student's t = 2.859; P less than or equal to 0.021). Baseline values at 02:00 were compared with levels at the same time of day after exposure to 2 hours of 200 lux of light (30.6 +/- 13.1 pg/ml), which caused an average suppression of 54.8% in melatonin levels. One animal did not show light suppression. Results indicated that the squirrel monkey suppressant response to light, as well as baseline values of melatonin, varied between animals. PMID- 2231271 TI - Choline acetyltransferase in bovine pineal gland. AB - Recent studies from our laboratories have shown that the bovine pineal gland contains a muscarinic cholinergic receptor with a Kd value of 0.423 +/- 0.010 nM and a Bmax value of 69.75 +/- 20.91 fmol/mg protein. In order to substantiate further the possible existence of a pineal cholinergic transmission, we have measured the activity of choline acetyltransferase and delineated its kinetic properties in the bovine pineal gland. This enzyme exhibited an activity of 0.0339 +/- 0.0042 nmol/mg protein/min. Furthermore, the bovine pineal choline acetyltransferase possessed a Km value of 124.86 +/- 24.06 microM and a Vmax value of 0.0598 +/- 0.0034 nmol/mg protein/min for acetyl CoA, and a Km value of 3.11 +/- 0.94 mM and a Vmax value of 0.0155 +/- 0.0016 nmol/mg protein/min for choline. The presence of muscarinic cholinergic receptors along with a specific choline acetyltransferase are supportive evidences that the bovine pineal gland may receive cholinergic innervation. PMID- 2231272 TI - Correlation between salivary and serum melatonin: dependence on serum melatonin levels. AB - Saliva and serum samples were collected from eight healthy volunteers every two hours during a 26-hour period. Melatonin concentrations were measured by radioimmunoassay after chloroform extraction using radioiodinated melatonin as a tracer. Five of the subjects had high serum melatonin levels at night (peak levels higher than 75 pg/ml); in three subjects the highest serum melatonin concentration was 20-40 pg/ml. All subjects had low levels (less than 10 pg/ml) during the day. The correlations between salivary and serum levels were calculated. The regression line y = 0.33x + 3.7 pg/ml, r = 0.95, P less than 0.001, was obtained for all detectable value pairs (n = 73). The regression and correlation coefficients were almost equal for the peak values of melatonin and during the rising and descending phases of the secretion patterns. However, no significant correlation was found between low daytime salivary and serum concentrations when calculated separately. In the five high-secretors the melatonin levels in saliva reflected reliably the changes in serum, but in the three low-secretors the correlation between salivary and serum melatonin was not significant. The proportion of melatonin found in saliva decreased with increasing serum melatonin levels. Circadian rhythm parameters were estimated by single cosinor analysis. The acrophases did not differ significantly within a subject in the concomitant measurements of serum and salivary melatonin. The measurements of salivary melatonin levels seem valid for studies on melatonin rhythms, but the melatonin concentrations measured in saliva do not always consistently reflect the absolute concentrations in blood. PMID- 2231273 TI - Pineal gland free amino acids and indoles during postnatal development of the rat: correlations in individual glands. AB - Free amino acids and indoles were measured by HPLC in single pineal glands of 5-, 10- and 20-day-old rats sacrificed during mid-light and mid-dark at each age. Melatonin was detectable in neonates (5-day-old), but day vs night differences in indole constituents did not occur until 10 days of age. Free amino acid steady state levels were high in neonates and there was a tendency for reversal of day vs night differences coinciding with the onset of circadian rhythmicity in indole biosynthesis. High correlations (r greater than 0.85) existed for taurine vs. glutamate in individual glands regardless of age and time of sacrifice. These findings suggest that taurine and glutamate are biochemically interrelated and that developmental changes in amino acid metabolic pools reflect functional innervation of the gland. PMID- 2231275 TI - Thymidine incorporation by chick pineal glands as studied by pulse-labelling in vitro. AB - We have studied the pattern of variations in extent of thymidine incorporation during pulse-labelling in cultured chick pineal glands. During the first 24-30 h in culture the extent of pulse-labelling varied in parallel with the cycle in cumulative incorporation. Pulse-labelling was seen during the period of apparent arrest of cumulative incorporation. However, it was probably "masked" by the SD of assays of cumulative incorporation and represented a minor, but distinct, process of thymidine incorporation. The pattern of variation in extent of pulse labelling was qualitatively consistent under a wide variety of conditions. Control of this pattern appeared to be different from that of the circadian rhythm in cumulative thymidine incorporation. PMID- 2231274 TI - Propranolol blockade of short photoperiod-induced gonadal regression: modification by melatonin injections or implants. AB - Male Syrian hamsters were exposed to short photoperiods (10L:14D) for ten weeks and received daily ethanolic saline (1:10), propranolol (125 micrograms, sc) or melatonin (25 micrograms, sc) injections at 16:45. Some hamsters also received melatonin implants (1 mg in 24 mg beeswax, sc) every two weeks in addition to the above treatments. Testicular weights were determined at the beginning, every three weeks, and at the end of the experiment. Serum hormone levels, hypothalamic amine levels and cortical amine levels were also determined at the conclusion of the experiment. Propranolol prevented the decline in testes weight produced by short photoperiod (P less than 0.001 versus control). Propranolol was not able to prevent daily injections of melatonin from producing gonadal regression. Melatonin implants blocked testicular regression produced by both short photoperiod and melatonin injections. No differences in hypothalamic or cortical amine levels were observed between the treatment groups. These results add further support to the suggestion that propranolol is acting at the pineal gland preventing melatonin synthesis and not at a post-pineal central site which would affect melatonin binding and action. PMID- 2231276 TI - Familiarity and differences in self- and other-representations. AB - Two studies compared representations of the self and of other people, guided by the hypothesis that self-other differences derive from one's greater familiarity with oneself than with others. For the first study, participants wrote open-ended descriptions of themselves, a familiar person, and an unfamiliar person, which were analyzed for the amount and types of information they contained and for consistency in specific content across stimulus people and situations. Participants returned for a second study 1 week later and made timed judgments of information taken from their written protocols. The response latencies for these judgments were used to infer how information is organized in self- and other concepts. The results supported most of the predicted self-other differences, but almost all were matched by differences between familiar and unfamiliar others. Familiarity does provide a parsimonious explanation for many self-other differences. PMID- 2231277 TI - "Do I know you?" The role of significant others in general social perception. AB - This research used an idiographic method to examine the proposition that significant others are mentally represented as well-organized person categories that can influence social perception even more than representations of nonsignificant others, stereotypes, or traits. Together, Studies 1 and 2 showed that significant-other representations are richer, more distinctive, and more cognitively accessible than the other categories. Study 3 replicated the accessibility data and gauged inferential power by indirectly activating each category in a learning trial about a fictional person and then testing recognition memory. The results showed that participants made more category consistent false-positive errors about targets who activated significant others vs. any other category. This constitutes the first experimental demonstration of transference and has implications both for social categorization and for basic personality processes. PMID- 2231278 TI - Credit and blame among American and Japanese children: normative, cultural, and individual differences. AB - Japanese and American 5th graders (N = 593 children, 198 American and 395 Japanese) assigned credit and blame to good and bad classroom deeds and performances. Theoretically, a morality of aspiration involves assigning more credit for a good deed than blame for a corresponding bad deed; a morality of duty involves assigning more blame than credit. In both countries academic achievement norms were most consistent with aspiration, moral norms were judged as duties, and procedural norms were intermediate. Japanese children's responses were more consistent with aspiration than those of Americans. Analyses also explored cultural versus individual differences in sanctioning. The conclusion addresses the relevance of the concept of aspiration to the study of achievement and other norms. PMID- 2231279 TI - Perceived social support, self-efficacy, and adjustment to abortion. AB - Prior to their having a 1st trimester abortion, women's perceptions of social support from their partner, family, and friends and self-efficacy for coping were assessed. Depression, mood, physical complaints, and anticipation of negative consequences were measured after the 30-min recovery period. As predicted, perceived social support enhanced adjustment indirectly through its effects on self-efficacy. Women who perceived high support from their family, friends, and partners had higher self-efficacy for coping. Higher self-efficacy, in turn, predicted better adjustment on the psychological measures but not on the physical complaint measure. No direct path between social support and adjustment was observed. In addition, women who told close others of their abortion but perceived them as less than completely supportive had poorer postabortion psychological adjustment than either women who did not tell or women who told and perceived complete support. PMID- 2231280 TI - Rational selective exploitation and distress: employee reactions to performance based and mobility-based reward allocations. AB - Prior research has demonstrated that allocators frequently distribute greater rewards to persons with high professional and geographic mobility than to persons with constrained mobility, especially among the very competent. This phenomenon has been termed rational selective exploitation. Do the recipients of such allocations actually experience this distribution rule as unjust and distressing, or is it a misnomer to refer to this phenomenon as exploitation? Two studies were conducted to explore this question. Study 1 was a laboratory experiment in which we manipulated relative performance level, relative mobility level, and allocation standard: performance based versus mobility based. Study 2 was a cross sectional survey of actual employees in which subjects reported the degree to which performance and mobility were the basis for pay decisions at their places of employment, as well as the degree to which they perceived each standard to be fair. Both studies demonstrated that people regard mobility-based allocations as less fair and more distressing than performance-based allocations. Furthermore, the degree of distress resulting from mobility-based allocations is greater among persons who are disadvantaged by that standard: among people with constrained mobility, especially those who perform at high levels. These findings provide good support for the assertion that so-called rational selective exploitation is indeed distressing to employees. Reactions to this form of distress are also explored, and the implications of these findings for the allocation process are discussed. PMID- 2231281 TI - Similarity of outcomes, interdependence, and conflict in dating relationships. AB - Dating couples (N = 59) participated in a longitudinal study of hypotheses derived from interdependence theory. Whether each partner's activity preferences and similarity of preferences, weighted by liking, would predict joint activity participation was examined. Preferences explained participation better than similarity, and own preferences predicted better than other's preferences. We hypothesized that conflict would increase with the strength of preferences but would decrease with similarity. The hypothesis concerning similarity was confirmed for some activities. Participation, similarity, and conflict explained relationship satisfaction and stability, but participation predicted better for men, whereas conflict and similarity predicted better for women. The findings support the theory but suggest that interdependence problems vary by activity type and gender. Three patterns are discussed: turn taking, unresolved competition, and cooperation. PMID- 2231282 TI - Effect of actor depression on observer attributions: existence and impact of negative attributions toward the depressed. AB - This experiment examined whether others explain the successes and failures of depressed versus nondepressed people differently and how these attributions are related to affective and behavioral reactions to a request for psychological help. Ss reported attributions about the success and failure experiences of hypothetical depressed and nondepressed people. Ss also responded to a hypothetical request for psychological help by indicating their attributions, affective reactions, willingness to help, and desire for future social contact. As hypothesized, Ss displayed more negative attributions toward depressed people. Replicating prior research, Ss responded to the depressive's request for help with mixed emotional and behavioral reactions. Path analyses revealed that attributions influenced affective reactions, which influenced willingness to help; but a more complex pattern emerged from the analysis of desire for future social contact. Results are discussed in terms of the interpersonal impact and possible causes of negative attributions about the experiences of depressed people. PMID- 2231283 TI - Coping as a personality process: a prospective study. AB - The study tested the proposition that coping is personality in action under stress. Using a stressful medical school entrance examination, the study examined (a) whether neuroticism emerged in coping patterns over time and (b) whether the influence of neuroticism on coping accounted for changes in anxiety and examination performance. Fifty premedical students reported their coping efforts at 35 days before, 10 days before, and 17 days after the examination. They provided daily reports of anxiety for 35 days surrounding the examination. Neuroticism influenced coping efforts and increases in daily anxiety under stress. Two types of coping, wishful thinking and self-blame, explained over half the relationship between neuroticism and increases in preexamination anxiety. Consistent with previous research, neither neuroticism nor specific coping efforts influenced examination performance. PMID- 2231284 TI - Self-esteem and clarity of the self-concept. AB - This article examines the association between evaluative and knowledge components of the self. Four studies tested the hypothesis that the self-concepts of low self-esteem (LSE) people are characterized by less clarity or certainty than those of high-self-esteem (HSE) people. LSE Ss exhibited less extremity and self reported confidence when rating themselves on bipolar trait adjectives (Study 1), less temporal stability in their trait ratings over a 2-month interval (Study 2), less congruence between their self-concepts and their subsequent perceptions of situation-specific behavior and memory for prior behavior (Study 3), and less internal consistency, lower self-rated confidence, and longer reaction times when making me/not me responses to pairs of opposite traits (Study 4). Alternative accounts of the results and the implications of self-concept clarity for understanding the pervasive impact of self-esteem on behavior are discussed. PMID- 2231285 TI - Intrinsic religiousness and religious coping as life stress moderators for Catholics versus Protestants. AB - Two prospective studies were conducted to test the stress-moderating effects of intrinsic religiousness and overall religious coping on the depression and trait anxiety of Catholic and Protestant college students. Both studies found a significant cross-sectional interaction between controllable life stress and religious coping in the prediction of Catholics' depression, with religious coping serving a protective function at a high level of controllable negative events. Both studies also found a significant prospective interaction between uncontrollable life stress and intrinsic religiousness in the prediction of Protestants' depression; the relationship between uncontrollable stress and depression was positive for low intrinsic Protestants, flat for medium intrinsic Protestants, but negative for high intrinsic Protestants. The findings are discussed in terms of their implications for the role of religion in life stress adjustment. PMID- 2231286 TI - Reasoning about the self and relationships in maturity: an integrative complexity analysis of individual differences. AB - This study examined age (35-55 versus 65-85), gender, and self-concept orientation differences in reasoning about the self, relationships, and morality, on the basis of the theorizing of Gilligan (1982). Participants were interviewed about general relationship issues, a specific relationship, and about the self. Reasoning was scored for integrative complexity (Suedfeld & Tetlock, 1977). Life experience measures and the standard Kohlberg justice reasoning index were obtained. Results showed gender differences in the connectedness of the self concept for middle-aged, but not older, adults. No age or gender differences in the complexity of relationship reasoning or in justice reasoning were found. Those with more connected self-concepts reasoned in more complex ways about relationships and about the self. PMID- 2231288 TI - Methodological issues in AIDS clinical trials. A symposium sponsored by the National Institute of Allergy and Infectious Diseases and Food and Drug Administration. Bethesda, Maryland, November 20-21, 1989. Proceedings. PMID- 2231287 TI - Appraised changeability of a stressor as a modifier of the relationship between coping and depression: a test of the hypothesis of fit. AB - The goodness of fit among the appraised changeability of a stressor, coping, and depression in people with psychiatric, physical health, work, and family problems was examined (N = 746). It was expected that problem-focused coping (as opposed to emotion-focused coping) would be used more and be more adaptive in situations appraised as changeable as compared with situations appraised as not changeable. Although few relationships existed between appraisal and coping, tests of fit between coping and depressed mood (maladaption) were much stronger. In people with nonpsychiatric conditions, problem-focused coping and depressed mood were negatively related when a stressor was appraised as changeable but were unrelated when a stressor was appraised as not changeable. Emotion-focused coping was positively related to depression when a stressor was appraised as changeable. No general relations were observed in the people with psychiatric conditions. PMID- 2231289 TI - The need for early randomization in the development of new drugs for AIDS. PMID- 2231290 TI - Methodological issues in AIDS clinical trials. Issues in the testing of drug combinations. PMID- 2231291 TI - Methodological issues in AIDS clinical trials. Application of the combination index method in the design of a clinical antiretroviral trial: ACTG 068. PMID- 2231292 TI - Methodological issues in AIDS clinical trials. Intent-to-treat analysis. PMID- 2231293 TI - Methodological issues in AIDS clinical trials. Data monitoring and sequential analysis--an academic perspective. PMID- 2231294 TI - Methodological issues in AIDS clinical trials. Analysis and interpretation of trial results. Discussion. PMID- 2231295 TI - Methodological issues in AIDS clinical trials. Discussion. Incorporation of trial results into clinical practice. PMID- 2231296 TI - Design considerations for AIDS trials. PMID- 2231297 TI - Methodological issues in AIDS clinical trials. Introduction. PMID- 2231298 TI - Implications of an alternative approach to dose-response trials. PMID- 2231299 TI - Methodological issues in AIDS clinical trials. Discussion. Design of clinical trials--approaches to clinical trials design. PMID- 2231301 TI - Rationale for variations in clinical trial design in different HIV disease stages. PMID- 2231300 TI - Methodological issues in AIDS clinical trials. Statutory and regulatory framework for drug approval. PMID- 2231302 TI - AIDS in intravenous drug users: issues related to enrollment in clinical trials. PMID- 2231304 TI - Practical issues and considerations in the design of clinical trials for HIV infected infants and children. PMID- 2231303 TI - Evaluation of the AIDS dementia complex in clinical trials. AB - The AIDS dementia complex (ADC) is one of the most common and important causes of morbidity associated with infection by human immunodeficiency virus type 1 (HIV 1). The evaluation of ADC in clinical trials is significant not only because of the clinical impact of this syndrome, but also because of the value of measuring its cardinal features as an index of drug efficacy and because of its emerging role as a major clinical end point. The objectives of therapy include both prevention of ADC in the presymptomatic patient and alleviation of established disease. At present, the pathogenesis of ADC is incompletely understood in several critical aspects, particularly the processes underlying the clinical manifestations of central nervous system (CNS) HIV-1 infection and, further, how such processes are related to systemic disease. Consequently, it is not yet clear to what extent, or in which patients, it is necessary to achieve "therapeutic" drug levels within the CNS. Nevertheless, the assessment of ADC prevention and treatment relies principally on the complementary approach of neurological examination for diagnosis and neuropsychological testing for quantitative serial measurement of treatment effects. Additionally, surrogate markers in cerebrospinal fluid (CSF) may hold promise for objective, rapid assessment of treatment response and dose adjustment. Other measurements, including more routine CSF analysis, neuroimaging, and neurophysiological assessments, are used principally for differential diagnosis rather than for monitoring ADC status. Accumulating experience with available antiviral agents suggests that ADC can be effectively prevented and treated, at least for some period of time, and that assessment of this condition is indeed a valuable approach for measuring antiviral therapy. PMID- 2231305 TI - Methodological issues in AIDS clinical trials. Discussion. Design of clinical trials--end points. PMID- 2231307 TI - Methodological issues in AIDS clinical trials. Discussion. Design of clinical trials--active control (equivalence) trials. PMID- 2231306 TI - Evaluation of active control trials in AIDS. AB - In settings in which effective standard treatment exists, active control trials provide an ethically appealing approach to evaluating experimental therapies by allowing all patients to be randomized either to a promising new regimen or to the standard as it would be routinely delivered in clinical practice. This paper describes an appropriate statistical approach for analyzing the clinical efficacy of new treatments in such studies. Confidence intervals for the relative efficacy of the new treatment vis-a-vis standard therapy are used to provide information required to determine whether the experimental treatment has an improved therapeutic index. Desirable properties of this approach include the ability to implement standard group sequential guidelines for early trial termination, the ability to use valid surrogates for hard clinical outcomes, and the availability of straightforward formulas for sample size calculations. PMID- 2231308 TI - Effectiveness of multidrug therapies in tuberculosis. PMID- 2231309 TI - [Studies on anti-tumor activity of crude drugs. III. The effects of decreasing resistance of cancer cell in long-term in vitro screening test with aqueous extracts of some crude drugs]. AB - When human cancer cell (JTC-26) was subjected to aqueous extracts of some crude drugs for a long time, its drug resistance against the cancer cell decreased. However, the cancer cell with decreased resistance recovered its proliferative power completely when cultured without the addition of the specimens. This revealed that the drug resistance-decreasing action or cytostatic action was entirely reversible. On the other hand, chemical anticancer agents increased cancer cell resistance, but the cancer cell did not recover itself and then perished when damage was given to it to a certain extent. Normal cell showed no decrease in resistance to the aqueous extracts. PMID- 2231310 TI - [The pharmacokinetics of pranoprofen in humans]. AB - The pharmacokinetics of pranoprofen, 2-(5H-[1]benzopyrano[2,3-b]pyridin-7-yl) propionic acid (I) in humans were examined. 1-O-Acylglucuronide of I (II) and its isomer (III) were isolated from the human urine after oral administration of I. The stability of II was tested in order to establish the suitable conditions for the storage and handling of biological samples. Maximum stability of II was found at pH 3-4. Unchanged drugs, II and III were detected in the human plasma after oral administration of I. Plasma concentrations of these compounds reached the maximum at 1-2 h after the administration and thereafter decreased biphasically. From the urinary sample, 1-O-acylglucoside of I (IV) was detected in addition to unchanged drugs, II and III. Within 24 h after dosing, 1.3, 84.0, 7.0 and 0.6% of the dose were excreted as I, II, III and IV, respectively and the total urinary excretion amounted to 92.9% in term of unchanged drug. PMID- 2231311 TI - [Study of crystalline drugs by means of a polarizing microscope. XI. Analysis of the particle size distribution of a principle agent in a trituration of phenytoin]. AB - By the immersion method with a polarizing microscope a principle agent phenytoin was identified from its 10 times trituration containing vehicles such as lactose and starch. A particle size distribution of phenytoin crystals in its trituration was determined by observing one of the habit parameters b from all the detectable particles of phenytoin under a microscope in a suspension of an immersion oil, nD: 1.555, in which phenytoin crystals having key refractive indexes, n1: 1.606, n2: 1.631, were clearly detectable from other vehicles. By the similarity of crystal habits in the same lot the particle size distribution of phenytoin crystals in its trituration was calculated from the values of observed parameter b and average values of habit coefficients, T(square root of ab/c): 2.004, L(b/a): 2.545, which were obtained from some previously identified phenytoin crystals. PMID- 2231313 TI - Analysis of T-2 toxin metabolites in tissues and excreta of rats. AB - In previous journal articles, we have demonstrated that microsomal carboxyesterase deacetylated specifically the C-4 acetyl residue of T-2 toxin and the resulting HT-2 toxin was an end product of the in vitro system. In an attempt to confirm this evidence in the in vivo system, we have analyzed the metabolism of T-2 toxin in rats. Male rats received orally 2-5 mg/kg of T-2 toxin, and the contents of T-2 toxin, HT-2 toxin, and neosolaniol in the liver, kidney, and serum were analyzed by using GLC method. The data revealed that HT-2 toxin was found in the liver shortly after the administration, and neither T-2 toxin nor neosolaniol was detected in the tissues. Blue spot test on TLC by using 4-(p nitrobenzyl)pyridine revealed the presence of HT-2 toxin and T-2 tetraol in the urine and HT-2 toxin in the feces. PMID- 2231312 TI - Primary liver cancer and aflatoxin intake in Transkei. AB - Transkei has an intermediate primary liver cancer (PLC) rate that is unusually high for a corn-based subsistence economy. The situation is complicated by a very high esophageal carcinoma incidence rate and known exposure to hepatocarcinogenic N-nitrosamines. A total of 623 cooked food samples were collected from two northeastern and two southern districts over two seasons, in a single-sample grid pattern, for aflatoxin analysis. Aflatoxin B1 was quantitated in 26% of all samples during 1976, resulting in a mean contamination rate of 0.65 microgram/kg wet food. Mean contamination during 1977 was 0.66 microgram/kg, and 24% of samples were positive. Thus for both years a mean aflatoxin B1 intake of 16.5 ng/kg body weight per day was calculated. When the data were plotted on our published PLC incidence-aflatoxin intake graph constructed with standardized data from four countries, Transkei was well within the 95% confidence limits. Individual district comparisons are handicapped by as yet inadequate PLC incidence data, but rank order correlations (rs) between aflatoxin intakes and the PLC incidence in goldminers originating from the study districts were significant (P less than .05). Corn was the basis of 95% of the meals and was also the main source of contamination. Six of 23 samples of home-brewed corn beer were positive for aflatoxin, resulting in an overall contamination of 0.69 microgram/L. PMID- 2231314 TI - Antimicrobial action of roquefortine. AB - Roquefortine, a secondary metabolite of Penicillium roqueforti, was investigated with regard to its effect on microorganisms. The growth of gram-positive bacteria was inhibited by roquefortine, whereas gram-negative bacteria were not influenced at all. The minimal inhibitory concentrations for gram-positive organisms were about 80 micrograms/mL cells on the average. The sensitive bacterium Corynebacterium flaccumfaciens was chosen for characterizing the antimicrobial action of the mycotoxin. Addition of low roquefortine concentrations at the beginning of bacterial growth resulted in prolongation of both the lag and logarithmic phases. High toxin concentrations (100 micrograms/mL cells) added to growing cells caused prolongation of logarithmic growth and decreased maximum cell density. This effect could be abolished when the cells, inhibited during the logarithmic growth, were centrifuged, washed, and transferred into fresh nutrient medium. In that case a second prolonged lag phase occurred, but the following logarithmic growth was comparable to normal cell growth. These results indicate that the antimicrobial effect of roquefortine is bacteriostatic but not bactericide. The growth inhibition might be a consequence of a roquefortine influence on bacterial respiration. The uptake of oxygen was reduced to 50% at a toxin concentration of 100 micrograms/mL cells. PMID- 2231315 TI - The mode of action of ochratoxin A in acute enteritis in rats. AB - The mode of action of ochratoxin A(OCT A) was studied in male Wistar rats in connection with the development of acute enteritis. Acute enteritis in the duodenum and jejunum identical with that induced by oral administration was also induced by parenteral application at the dose level of 15 mg/kg OCT A and was completely inhibited by ligation of the choledochus. Direct application of OCT A into the jejunal blind sac lumen constructed by two ligations induced severe inflammation in situ and also revealed remote action to the duodenum and jejunum where separated from the blind sac by ligation. This remote action was inhibited by ligation of the choledochus. These results clearly demonstrated the enterohepatic circulation of OCT A. The ileal injection also revealed remote action of OCT A, although no pathologic change was caused in the ileal mucosa. The results obtained suggest that the enteritis may be induced by direct exposure of OCT A to the intestinal mucosa without metabolic activation, although certain participation of ochratoxin alpha to accelerate the inflammation was suspected. PMID- 2231316 TI - Transplacental transfer of T2-toxin: pathological effect. AB - Radioactivity was recovered in fetuses of pregnant rats following administration of radioactive T2-toxin. The transplacental effects of T2-toxin were studied by ip administration or oral feeding of pregnant rats at doses equivalent to natural contaminations and compatible with the maintenance of pregnancy. Body weights of the newborn rats from treated females were similar to the body weights of the control animals but their thymuses were atrophic. This atrophy was reversible in one week. Since the measurement of antibody production for fetuses and newborns is not feasible, the lymphoblastic response to mitogen of the splenic and thymic cells of baby rats from treated and control females was tested. At 4 and 6 days after birth, a good response to PHA for the thymic cells of the mother treated young rats was observed. Histological examination of the thymus showed that one day after birth the cortex was atrophic while the medulla was proliferative; on day six the situation was reversed. For the spleen, both B and T cells were impaired and their responsiveness to PHA and LPS decreased. On days 1 and 6, the periarteriolar sheats, as well as the follicles, appeared atrophic. These results show that T2-toxin easily passes the placental barrier and that T2-toxin injection or feedings at levels (2 ppm) similar to those in naturally contaminated foods, produced an impairment of the immune system of the newborn. PMID- 2231317 TI - Synergistic effects of T-2 toxin and a low protein diet on erythropoiesis in mice. AB - Young male Swiss mice fed on a semipurified diet containing 8% protein and 10 ppm of T-2 toxin developed erythroid hypoplasia within 2 weeks. Red blood cell counts declined to 36% of control values by 6 weeks but had risen to 45% of control values by 8 weeks. Between 4 and 8 weeks, erythropoietic tissues regenerated and reticulocyte counts became greatly elevated. The toxin-free semipurified diet was adequate for normal growth and did not cause anemia in control mice fed either ad lib, or at a restricted rate. Anemia did not occur in mice fed the 10-ppm level to T-2 toxin in either a semipurified diet containing 16% protein, or in a balanced natural-ingredient mouse diet. These observations demonstrated that the inhibitory effect of T-2 toxin in erythropoiesis in mice was transient, and depended on the nutritional composition of the diet. PMID- 2231318 TI - Contribution of pharmacokinetic computerized simulations in toxicological approach of ochratoxin A. AB - An open two-compartment model described the fate of ochratoxin A in the rat. Curves of toxin quantities contained in the two compartments and predicted plasma concentrations following 1-, 2-, or 3-daily administrations were simulated by use of mathematical expressions programmed for a digital computer. These studies clearly showed residues of ochratoxin A in deep compartment tissues such as muscle, fat, and skin. The pharmacokinetic profiles of ochratoxin A in pigs and broilers were also investigated and discussed. PMID- 2231319 TI - Tissue deposition and passage into eggs of ochratoxin A in Japanese quail. AB - Laying Japanese quail (Coturnix coturnix japonica) were given single oral doses of 0, 1, 5, and 20 mg of ochratoxin A (OA) per kg of the body weight. After 6, 12, and 24 hours and 2, 3, 4, 5, 6, and 7 days an appropriate number of birds was sacrificed and OA in blood, muscles, liver, kidney, abdominal yolks, and collected eggs was measured. The highest concentration of OA was found in kidneys and the lowest in muscles. Four days following the application, OA could still be detected in kidney, liver, muscles, yolk, and eggs, although even after six days traces of OA were found in the muscles of birds given 20 mg/kg. PMID- 2231320 TI - Hydralazine dose-response curve analysis. AB - A multicenter, parallel, double-blind, 181-patient study compared the safety and antihypertensive efficacy of immediate-release (IR) and extended-release (ER) hydralazine. After 2 to 4 weeks on diuretic, patients were maintained on diuretic and randomized to a hydralazine treatment regimen: IR thrice daily, ER twice daily, or ER once daily. Daily doses of hydralazine were 75, 150, or 300 mg. Although designed as a titration study, important dose-response data were available for analysis with nonlinear mixed effect modeling (NONMEM). Sitting diastolic blood pressure (BP) was selected as the response variable. Several factors were tested for importance, including body weight, time (week) effects, concomitant beta-blocker (BB) therapy, acetylator class, and treatment regimen. All factors were important (p less than 0.05) except treatment regimen (p greater than 0.30). The maximum antihypertensive response (Emax) to hydralazine was 9.4 mm Hg. The daily dose that elicited 50% of the maximum response (D50) was 0.87 mg/kg for slow acetylators and 1.68 mg/kg for fast acetylators. BP fell 0.52 mm Hg per week independent of other effects, and concomitant BB therapy induced a drop of 6.6 mm Hg in addition to hydralazine, diuretic and week effects. NONMEM's use assisted in evaluations and provided information not obtainable through traditional means. PMID- 2231321 TI - Comparison of methods to calculate cyclosporine A bioavailability from consecutive oral and intravenous doses. AB - The pharmacokinetics of cyclosporine A (CyA) was studied in 21 uremic patients. The plasma concentrations after an oral dose and a subsequent short-term infusion were analyzed simultaneously by nonlinear regression. Bi- and triexponential disposition models with either zero- or first-order absorption were fitted to the data. A triexponential disposition model with zero-order absorption was generally found to best describe the concentration-time profile. The bioavailability and clearance were estimated to be 0.24 +/- 0.10 and 21 +/- 8 L/hr, respectively. These values differed only marginally from those predicted by the other models. Similar bioavailability estimates were also obtained from a three-compartment model where elimination was assumed saturable, from a deconvolution procedure, and from analyses based on blood concentrations. Markedly higher bioavailabilities (0.34 +/- 0.13) were obtained when a model-independent AUC correction procedure, commonly used to calculate CyA bioavailability, was used. The difference could not be explained by poor description of data in the model dependent analyses, but rather by overestimation in the model-independent analyses mainly due to errors in the extrapolations used. Thus, by the simultaneous fitting procedure, which is a new approach for estimating CyA bioavailability, drawbacks of the AUC correction procedure could be avoided. Further, future studies of CyA bioavailability could be designed with a markedly shorter and more convenient length of time if analyzed by the proposed method. PMID- 2231323 TI - Relationship between train-of-four ratio and first-twitch depression during neuromuscular blockade: a pharmacokinetic/dynamic explanation. AB - Fade, as measured by train-of-four, lags behind twitch depression during the initial phase of nondepolarizing neuromuscular blockade, i.e., the ratio of the fourth to first twitch height in a train (T4/T1) is greater at the onset of the block than during spontaneous recovery for the same level of first twitch depression. We believe that these data can be explained by picturing the muscle as having localized regions that respond much more slowly than the rest, leading to a delay in drug effect in that area, especially when the drug concentration rises rapidly as during bolus administration. This was modeled by computer as a muscle of 15 compartments distributed in a log-normal fashion according to equilibration rate. Experimental data consisting of the time course of first twitch and train-of-four ratio were fitted by nonlinear regression to the model. A good fit was obtained with a median equilibration time t1/2 of 3.3 min and a standard deviation of 2.1. The difference between train-of-four during onset and regression of block at the same level of first twitch depression was reproduced. PMID- 2231322 TI - Kinetic analysis of the dose-dependent hepatic handling of 1-anilino-8 naphthalene sulfonate in rats. AB - The dose dependency in the hepatic transport of an anionic fluorescent dye, 1 anilino-8-naphthalene sulfonate (ANS), was investigated by measuring the plasma disappearance and biliary excretion in rats. Bulk of the administered ANS distributed into the liver at 10 min after iv bolus injection. The plasma disappearance curves of ANS were then kinetically analyzed based on a two compartment model, in which the ligand is eliminated only from the peripheral compartment (liver compartment). The total body clearance (CLtot) decreased with increasing dose of ANS. That is, the values of CLtot were 4.06 and 1.98 ml/min/per kg at the doses of 3 and 100 mumol/kg, respectively. The clearances of the uptake and sequestration processes (CLup and CLseq, respectively) for a total ligand were constant irrespective of dose, while the efflux clearance (CLeff) for a total ligand was increased by twofold with increasing dose. A mechanism for the increase in the CLeff value might be explained by a saturation of the ANS binding to the intracellular proteins. The hepatocellular distribution and the binding of ANS to cytosolic proteins were then determined. ANS mainly distributed to the cytosol fraction, and the unbound fraction in the cytosol increased from approximately 0.04 to 0.09 when the cytosolic concentrations of ANS increased from 40 to 900 microM, respectively. In spite of such increase in the unbound fraction in the cytosol, the CLseq values remained unchanged with increasing dose, suggesting that the saturation of sequestration clearance for unbound ANS might occur. Furthermore, the plasma disappearance curves of ANS at various doses were simultaneously analyzed based on three nonlinear kinetic models: Model I is a model incorporating both saturable intracellular binding and saturable sequestration; Model II is a model incorporating only saturable intracellular binding; Model III is the model incorporating only saturable sequestration. Goodness-of-fit evaluated by AIC value was best for Model I. Taken together, the nonlinearity in the plasma clearance of ANS was confirmed to be attributed to saturation of both its binding to cytosolic proteins and sequestration process. PMID- 2231324 TI - Experimental design and efficient parameter estimation in population pharmacokinetics. AB - A computer simulation technique used to evaluate the influence of several aspects of sampling designs on the efficiency of population pharmacokinetic parameter estimation is described. Although the simulations are restricted to the one compartment one-exponential model, they provide the basis for a discussion of the structural aspects involved in designing a population study. These aspects include number of subjects required, number of samples per subject, and timing of these samples. Parameter estimates obtained from different sampling schedules based on two- and three-point designs are evaluated in terms of accuracy and precision. These simulated data sets include noise terms for both inter- and intraindividual variability. The results show that the population fixed-effect parameters (mean clearance and mean volume of distribution) for this simple pharmacokinetic model are efficiently estimated for most of the sampling schedules when two or three points are used, but the random-effect parameters (describing inter- and intraindividual variability) are inaccurate and imprecise for most of the sampling schedules when only two points are used. This drawback was remedied by increasing the number of data points per individual to three. PMID- 2231325 TI - Estimation and inference in pharmacokinetic models: the effectiveness of model reformulation and resampling methods for functions of parameters. AB - It is well known that high parameter estimate correlations and asymptotic variance estimates can cause estimation and inference problems in the analysis of pharmacokinetic models. In this paper we show that analysis of three important functions of pharmacokinetic parameters, the half-life, mean residence time, and the area under the curve, can sometimes be greatly improved by reformulating the model to address collinearity and by using the bootstrap to form confidence intervals. The resultant estimators can be more accurate than the original ones, and resultant confidence intervals can be narrower. Of the three measures, the half-life estimator is much better behaved than the estimators of mean residence time and area under the curve under collinearity, suggesting that it (or measures like it) should be used more often. PMID- 2231326 TI - Formulation parameters affecting the preparation and properties of microencapsulated ion-exchange resins containing theophylline. AB - A method of microencapsulating theophylline ion-exchange resins with ethylcellulose was developed to produce smooth and uniform coats which were predominantly mononucleated. This was achieved by controlling the amount of ethylcellulose and the particle size, and through the use of a protective colloid, polyisobutylene. The rate of release of theophylline was influenced by the ion-exchange resin crosslinking, the amount of ethylcellulose, and the smoothness of the coat. Mesh size and polyisobutylene did not appear to affect the rate in a regular manner. It was found that the release rate from coated resins with low crosslinking followed a logarithmic plot, indicating membrane controlled release, whereas coated resins with high crosslinking fitted a t1/2 plot, suggesting particle diffusion control. PMID- 2231327 TI - Preparation and evaluation of sterically stabilized liposomes: colloidal stability, serum stability, macrophage uptake, and toxicity. AB - Sterically stabilized liposomes were produced by incorporating a nonionic surfactant, polysorbate 80 (Tween 80), into the lipid bilayer. The sterically stabilized liposomes exhibited a superior entrapment stability compared with surfactant-free liposomes (i.e., liposomes prepared with lipids and cholesterol). The sterically stabilized liposomes were stable at high calcium ion concentrations, and liposome-entrapped carboxyfluorescein was retained within the stabilized liposomes in the presence of serum for at least 5 h. The macrophage uptake of the sterically stabilized liposomes was comparable to that of liposomes containing lipids and cholesterol. The sterically stabilized liposomes were non toxic, in concentrations up to 3.0 mM, to macrophages. These results indicate that polysorbate 80 can be used to produce stable liposomes without changing the unique macrophage distribution of this drug delivery system. PMID- 2231328 TI - Tumor cell growth inhibition by liposome-encapsulated aromatic polyamidines. AB - Apart from its antiproteinase activity, the aromatic polyamidine TAPP-Br [the bromo derivative of 1,3-di-(p-amidinophenoxy)-2,2-bis-(p amidinophenoxymethyl)propane (TAPP-H)] is able to inhibit the in vitro growth of a variety of tumor cell lines, including human melanoma, and breast and kidney carcinoma. We have now shown that TAPP-Br can efficiently be encapsulated into egg phosphatidylcholine vesicles. When incorporated into these liposomes, the inhibitory effect of TAPP-Br is significantly enhanced compared with that of the free drug. Based on these promising results, a proposal is made for the delivery of this antiproliferative agent to tumor cells by using liposomes as the vehicle. PMID- 2231329 TI - Isobolographic assessment of the convulsant interaction between theophylline and caffeine or pentylenetetrazol in rats. AB - To characterize the convulsant interaction between theophylline and caffeine, male Sprague-Dawley rats received an iv infusion of one of seven different combinations of these drugs and of each drug individually until the onset of maximal seizures (which occurred within 30 to 40 min after the start of the infusion). The total infused doses of the two drugs and their respective concentrations in the serum, brain, and cerebrospinal fluid (CSF) were used for isobolographic analysis. The results are consistent with classical dose- and concentration-addition and do not suggest either antagonism or synergism. The potency ratio based on the doses or serum concentrations was appreciably different from that based on brain or CSF concentrations. The brain:serum and CSF:serum concentration ratios of caffeine were appreciably higher than those of theophylline. Similar experiments were performed with seven combinations of theophylline and pentylenetetrazol (PTZ) and with each of these drugs individually. This second set of experiments also yielded essentially linear isobolographs indicative of dose- and concentration-addition. The potency ratio based on CSF concentrations was appreciably different from ratio values based on doses, and from those based on brain or serum concentrations. These results illustrate a useful strategy for the characterization of pharmacodynamic drug interactions and highlight the importance of the choice of sampling site for determinations of the potency of drug. PMID- 2231330 TI - Effects of epinephrine pretreatment and solution pH on ocular and systemic absorption of ocularly applied timolol in rabbits. AB - The ratio between ocular and systemic drug concentrations describes the relative safety of ophthalmic dosage forms of the same drug in terms of its systemic side effects. In this study, we evaluated the effects of epinephrine pretreatment and solution pH on the aqueous humor:plasma and iris-ciliary body:plasma ratios of peak timolol concentrations after ocular application of timolol. Timolol eyedrops (5 mg/mL, 25 microL) were applied ocularly in pigmented rabbits. Raising pH of the eyedrops from 6.2 to 7.5 did not affect the ratio between ocular and systemic peak drug concentrations, since both ocular and systemic concentrations of timolol were increased. Administration of epinephrine (20 mg/mL, 50 microL) 5 min prior to timolol eyedrop administration reduced the peak timolol concentrations in plasma 65-80%. Epinephrine did not affect the ocular concentrations of timolol. The decreased peak concentrations in plasma were due to the conjunctival and nasal vasoconstricting effects of epinephrine and to the subsequent slower absorption of timolol. Our study demonstrates that compared with currently available eyedrops (pH 6.9), the ocular:systemic concentration ratio of ophthalmic timolol can be improved four- to sixfold in rabbits by combining epinephrine-induced conjunctival and nasal vasoconstriction and improved ocular absorption from pH 7.5 eyedrops. PMID- 2231331 TI - Moment analysis of drug disposition in kidney. II: Urine pH-dependent tubular secretion of tetraethylammonium in the isolated perfused rat kidney. AB - Effects of urine pH on the renal tubular secretion of an organic cation (tetraethylammonium, TEA) and an organic anion (p-aminohippurate, PAH) were investigated using the isolated erythrocyte-perfused rat kidney. The method was based on a multiple indicator dilution experiment and noncompartmental moment analysis. Treatment with sodium bicarbonate and sodium dihydrogen phosphate increased and decreased urine pH, respectively, but affected neither the condition of the perfused kidney nor the renal handling of albumin and inulin. In TEA studies, the increase of urine pH prolonged the mean residence time in renal epithelial cells (T cell) and reduced the apparent secretion intrinsic clearance, but did not influence the volume of distribution in the kidney (Vd drug). The decrease of urine pH did not affect these kinetic parameters. By contrast, PAH secretion was constant against the change of urine pH. Since any change in the basolateral membrane transport is reflected in Vd drug, the net transport from blood to cells can be regarded as similar under these treatments. On the other hand, the prolonged T cell of TEA with the increased urine pH suggested a slow transport from cells to lumen across the brush-border membranes. The present results coincide with the hypothetical mechanism that organic cations are secreted via an active transport system, coupled to the countertransport of H+ into cells. In conclusion, the present method is useful to separately evaluate the transmembrane transport across both sides of the renal epithelial cells in a morphologically intact kidney. PMID- 2231332 TI - Mechanism of nasal absorption of drugs. III: Nasal absorption of leucine enkephalin. AB - The nasal absorption of a model peptide, leucine enkephalin (LE), was studied in rats using an in situ technique in which 4 mL of perfusion solution was circulated. Leucine enkephalin (LE) was found to undergo hydrolysis to its major metabolite des-tyrosine leucine enkephalin (DTLE). The addition of 1% sodium glycocholate (SGC) to the perfusion solution resulted in an increase in the overall rate of disappearance of LE and a decrease in the rate of formation of DTLE. When LE was added to nasal washings (i.e., Ringer's buffer that was precirculated through the nasal cavity to extract enzymes), LE was found to form DTLE. When SGC or puromycin was added to the nasal washings prior to the addition of LE, the rate of conversion of LE to DTLE was significantly reduced, suggesting that these two agents can inhibit peptidase enzyme activity in the nasal cavity. Since the volume of the solution has been shown to influence the kinetics of absorption of drugs administered nasally, a new experimental technique, the in vivo-in situ technique, which utilizes small volumes of solution and simulates realistic use of nose drops, was employed to further examine the mechanism of absorption and hydrolysis of LE in rats. Leucine enkephalin (LE) dissolved in 100 microL of Ringer's buffer was placed in the isolated nasal cavities of rats. The disappearance of LE and the appearance of DTLE were followed by rinsing the nasal cavity with fresh buffer. Disappearance of LE was always accompanied by appearance of DTLE, and the fraction of LE converted to DTLE decreased as the concentration of LE increased, suggesting a saturable enzymatic process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231333 TI - Hydrolysis and acyl migration of a catechol monoester of L-dopa: L-3-(3-hydroxy-4 pivaloyloxyphenyl)alanine. AB - Hydrolysis and acyl migration studies on L-3-(3-hydroxy-4 pivaloyloxyphenyl)alanine (1, NB-355), which produced long-lasting plasma L-dopa levels after oral dosing, have been conducted. Compound 1 exists as pure 4-O pivaloyl-L-dopa in the solid state, but it converts rapidly to a mixture of the 3 and 4-O-isomers in solution. The rate of acyl migration increased with increases in pH and temperature, and the content of the 4-O-isomer in the equilibrium state was 53-59%. The hydrolysis rate of 1 to L-dopa (6) also increased with increases in pH and temperature, and accelerated steeply at neutral and alkaline pH. The rapid hydrolysis at neutral pH was not observed with O-pivaloyl-L-tyrosine (3), di-O-pivaloyl-L-dopa (4), or L-dopa methyl ester (5). Because of this chemical lability, 1 was hydrolyzed in rat plasma far faster than the other tested catechol esters. However, in rat intestinal homogenate at pH 6.0, 1 was hydrolyzed at the slowest rate among the tested esters, predominantly by a diisofluorophosphate (DFP)-sensitive esterase. Thus, 1 showed a unique in vitro profile on hydrolysis and acyl migration due to the existence of a neighboring hydroxyl group. The stability of 1 in the intestine might be essential for the long-lasting plasma L-dopa profile after oral dosing of 1. PMID- 2231334 TI - A study of the electrokinetic and stability properties of nitrofurantoin suspensions. II: Flocculation and redispersion properties as compared with theoretical interaction energy curves. AB - The stability and redispersion properties of nitrofurantoin dispersions are experimentally studied using simple but reproducible techniques. Solutions of different electrolyte concentrations and pH values are employed as dispersing media. The pH appears to be a determinant factor in the properties studied. Thus, with all the electrolytes considered (NaCl, CaCl2, and AlCl3, almost optimum redispersion was achieved when the pH was maintained close to neutrality. However, the important effect of AlCl3 as compared with the other electrolytes is also clearly demonstrated. Especially interesting are the results obtained when 0.1% Carbopol is added to the suspensions. The important effect of this polymer on the surface charge of nitrofurantoin, mainly at pH 7, manifests in excellent redispersion of the suspensions with either of the electrolytes employed. Using simple expressions that approximate the equations proposed in the DLVO theory of interaction between colloidal particles, the variation of the total interaction energy between nitrofurantoin particles is calculated as a function of interparticle distance. The results are compared with the experimental determinations of the sedimentation and redispersion properties of nitrofurantoin. Although some discrepancies between theory and experiments are found, the results indicate a reasonable agreement between the general features of both. PMID- 2231335 TI - Anticonvulsant properties of 3-oxo- and 3-imino-4-substituted 1,2,5 thiadiazolidine 1,1-dioxides. AB - Selectively substituted 3-oxo-4-substituted 1,2,5-thiadiazolidine 1,1-dioxides (2, four examples), and 3-imino-4-substituted 1,2,5-thiadiazolidine 1,1-dioxides (3, eight examples) have been evaluated in the maximal electroshock seizure (MES), subcutaneous pentylenetetrazole seizure threshold (scMet), and rotorod (Tox) tests. These compounds can be considered as sulfonyl analogues of hydantoins (1). In those cases where comparison between 1 and 2 (or 1 and 3) was possible, replacement of the central carbonyl group in 1 by a sulfonyl moiety led to a significant reduction or abolition of the anticonvulsant activity. PMID- 2231336 TI - Structure-pharmacokinetic relationships in a series of short fatty acid amides that possess anticonvulsant activity. AB - Valpromide (VPD) and valnoctamide (VCD) are two isomers which are aliphatic amides derived from short fatty acids that possess anticonvulsant activity. Our previous studies with VPD, VCD, and other related compounds showed that the biotransformation of these amides to their respective homologous acids is the key issue in their possessing pharmacological activity. In this study, we explored the structure--pharmacokinetic relationships of the following five isomers or analogues of VPD: diisproprylacetamide (DID), diallylacetamide (DAD), octanamide (OAD), ethylisobutylacetamide (EID), and dimethylbutylacetamide (DBD). In addition, the anticonvulsant activity of these compounds was evaluated and compared with that of VPD and VCD. No plasma levels of OAD could be detected after its iv administration. Octanamide (OAD) was very rapidly metabolized to its homologous acid, octanoic acid (OAA). Octanamide (OAD) was different from the other four amides investigated, having a high clearance (due to metabolic processes in the blood) and possessing the least anticonvulsant activity. All of the other amides were stable in blood and showed similar pharmacokinetic parameters. Unlike the other amides, DID and VCD did not metabolize to their respective homologous acids due to the fact that they had a substituted beta position in their aliphatic side chain. Our study showed that, despite similarities in the chemical structures of the amides investigated, significant differences were observed in their pharmacokinetics and in the fraction of the amide (fm) biotransformed to its homologous acid. These differences in fm values may, therefore, account for the observed differences in the respective pharmacological activities, in general, and in the extent of the anticonvulsant activity, in particular, of the amides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231337 TI - Computer automated structure evaluation of antifungal 1-vinylimidazoles, 1,2 disubstituted propenones, and azolylpropanolones. AB - The Computer Automated Structure Evaluation (CASE) program has been applied to a series of 1-vinylimidazoles, 1,2-disubstituted propenones, and azolylpropanolones exhibiting in vitro antifungal properties. Relevant molecular fragments were obtained for activity against the fungal strains Candida albicans, Aspergillus fumigatus, and Trichophyton asteroides. Fragments were utilized as descriptors to derive quantitative structure-activity relationships (QSAR) within each respective biological endpoint. A high degree of correlation was observed between fragments derived from C. albicans and A. fumigatus. The relevant activating and inactivating fragments from each of the respective biological endpoints analyzed are discussed. PMID- 2231338 TI - Stability and kinetics of degradation of imipenem in aqueous solution. AB - In weakly acidic solution, the broad-spectrum antibiotic imipenem undergoes complex oligomerization initiated by intermolecular carboxyl group attack on the beta-lactam group. In weakly alkaline solution, intermolecular reaction between the beta-lactam and formimidoyl groups occurs instead. Both beta-lactam and formimidoyl groups also hydrolyze at pH-dependent rates. Complex decomposition schemes were determined in kinetic studies at pH 4.0 and 9.0-9.5 using HPLC and mathematical models. The rates of the several initial reactions, calculated as functions of pH and imipenem concentration by fitting the models to kinetic data, fully account for imipenem decomposition rates throughout the neutral pH range. PMID- 2231339 TI - Radioimmunoassay of a new angiotensin-converting enzyme inhibitor (perindopril) in human plasma and urine: advantages of coupling anion-exchange column chromatography with radioimmunoassay. AB - Perindopril (P) is a prodrug whose active metabolite perindoprilat (PT) is an antihypertensive agent which acts by inhibition of angiotensin-converting enzyme (ACE). Anti-PT antiserum was produced in a rabbit immunized against PT that was covalently linked to bovine serum albumin. The radioligand is an iodinated (125I) derivative of PT-glycyltyrosinamide. Both the drug (PT) and the prodrug (P) are assayed in the same sample; PT is assayed as is and P is assayed after quantitative alkaline hydrolysis into PT. Certain data obtained from such assays suggest the occurrence in plasma and urine of a third immunoreactive component. A chromatographic fractionation of samples allowed us to isolate a new immunoreactive metabolite which was further identified as a glucuronide of PT (PT G). Therefore, the whole assay was carried out as follows: biological samples were fractionated by stepwise chromatography on a anion-exchange resin (the first fraction contained P, the second contained PT, and the third contained PT-G); and RIA was performed on fractions 2 and 3 as is, and on fraction 1 after alkaline hydrolysis. Performances and assessments of this method are presented together with an example of a pharmacokinetic profile. PMID- 2231340 TI - Determination of norethindrone stability on red delicious apples. AB - A stability-indicating assay procedure for the determination of norethindrone on the surface of Red Delicious apple slices was developed. The apple slice is homogenized in pH 10 borate buffer solution and norethindrone is then partitioned into chloroform using a diffusion chamber that has a membrane that is permeable to hydrophobic compounds separating the buffer and chloroform. An aliquot of the chloroform extract is then evaporated to dryness and reconstituted in tetrahydrofuran. The reconstituted sample is then chromatographed on a C18 reversed-phase column using a mobile phase consisting of water:tetrahydrofuran:methanol (63:26:11, v/v/v). Detection is in the UV range at 254 nm. The chromatographic system is specific for norethindrone in the presence of its autoxidation products. Stability data indicate that norethindrone is stable for up to 6 h on the surface of Red Delicious apples. PMID- 2231341 TI - Synthesis and antitumor activities of platinum complexes of unsymmetrical alicyclic diamines as carrier ligands. AB - The synthesis and biological activities of the platinum complexes of 2 aminomethylaziridine, 2-aminomethylazetidine, 2-aminomethylpyrrolidine, 2 aminomethylpiperidine as carrier ligands are described. The platinum complexes of 2-aminomethylazetidine and 2-aminomethylpyrrolidine are significantly effective against murine tumors. In particular, 2-aminomethylazetidine (1,1 cyclobutanedicarboxylato)platinum II (13) and 2-aminomethylpyrrolidine(1,1 cyclobutanedicarboxylato)platin um II (16) exhibited potent antitumor activity and were soluble in water, and their antitumor activities against Colon 26 carcinoma (sc-ip system) were superior to CBDCA and comparable to CDDP. PMID- 2231343 TI - Aging integumentary system. Podiatric review. AB - The authors present a concise review of age-related changes that occur in the skin and its derivatives, as they pertain to the podiatric practitioner. A brief discussion of wound healing and several common skin disorders that affect the elderly is also included. PMID- 2231342 TI - Isoxazoles. VI: Aspects of the chemical stability of a new naphthoquinone-amine in acidic aqueous solution. AB - Some aspects of the chemical degradation of N-(3,4-dimethyl-5-isoxazolyl)-4-amino 1,2-naphthoquinone were investigated as a function of pH and temperature. In acid and neutral pH, four main degradation products were identified: 2-hydroxy-1,4 naphthoquinone, 2-butanone, ammonia, and hydroxylamine. No significant buffer effects were observed for the buffer species used in this study. The pH-rate profile exhibited a specific acid catalysis which is important at pH values less than 3.5, and an inflection point at pH 1.10 corresponding to a pKa value. From Arrhenius plots, the activation energy was found to be 17.8 +/- 0.3 kcal/mol. PMID- 2231344 TI - Efficacy of twice-daily dosing of econazole nitrate 1% cream for tinea pedis. AB - This study was conducted to determine the efficacy of twice-daily applications of econazole nitrate 1% for the treatment of tinea pedis within a typical podiatric practice. The study showed that twice-daily application of econazole nitrate 1% is an effective therapy and is especially successful at preventing immediate fungal recurrence. PMID- 2231345 TI - Aneurysmal bone cyst of the cuboid. AB - Aneurysmal bone cysts are a rare entity encountered in podiatric medicine. The frequency of aneurysmal bone cysts distal to the ankle joint is low. The authors present a literature review of the etiologies and possible treatments of an aneurysmal bone cyst. An unusual case of an aneurysmal bone cyst in the cuboid is also presented. Only one other documented case of an aneurysmal bone cyst in the cuboid has been reported since 1967. PMID- 2231346 TI - First metatarsophalangeal joint arthrodesis. Treatment for sesamoid fractures. AB - Fractures of both hallucal sesamoids are not commonly reported in the literature. The authors address various surgical procedure choices and present a case history. In their case, conservative treatment failed; therefore, surgical intervention was elected, and fusion of the first metatarsophalangeal joint was performed. PMID- 2231347 TI - Human myiasis caused by Phormia regina in Pennsylvania. AB - A case of human myiasis caused by the black blowfly, P. regina, has been presented. Although various reports have documented the therapeutic effects of maggot infestation, infection and mortality by gas-forming anaerobic organisms also have been reported. The removal of maggots from a wound can be accomplished using various methods. The authors successfully used topical application of dichlorotetrafluoroethane. PMID- 2231348 TI - Lateral subtalar dislocation. A case report. PMID- 2231349 TI - Post-traumatic osteochondroma of the calcaneus. AB - Osteochondroma is the most common bone and cartilage tumor. It is usually congenital but may be related to trauma. A case of osteochondroma affecting the calcaneus, an unusual location for this lesion, is presented. Surgical excision appears to be as effective a cure in this location as in others. PMID- 2231350 TI - Epidermal inclusion cysts as a complication of nail surgery. AB - The authors presented a study of 93 patients who underwent a total of 183 nail matricectomies. The study was undertaken to establish the incidence of postoperative epidermal inclusion cysts, which was 5.5%. PMID- 2231352 TI - Research process. Preparing a research proposal. AB - The preparation of a research proposal is often a necessary step in the research process. Research proposals are used to secure permission to undertake a study, to ensure protection of subjects, to secure needed resources, and to achieve a refined perspective of the proposed study. This third article of a series of six on the research process describes the steps involved in preparing a research proposal, demonstrating a parallel to the research planning process. PMID- 2231351 TI - Urticaceae poisoning. PMID- 2231353 TI - Medicolegal case involving a bear paw. PMID- 2231354 TI - Tarsal tunnel syndrome. Comprehensive review of 87 cases. AB - The results of the study indicate that tarsal tunnel syndrome is a pathologic condition in which there are multiple etiologies, which in some cases are poorly defined. In order to arrive at a definitive diagnosis, all available tests, including pathology reports, are important. Where proper diagnosis is made and followed with appropriate adjunctive care, the probability of recurrence will be minimized. Statistical information in itself is of some value, because it may help the podiatrist to more clearly diagnose and treat the patients in whom vague or general symptoms may exist. PMID- 2231355 TI - Koenig total great toe implant. Preliminary report. AB - A new first metatarsophalangeal joint implant arthroplasty is described. The two component, titanium alloy and polyethylene prosthesis designed for weightbearing is noncemented and press-fit. Sixteen cases involving 18 implants were evaluated over 18 months with evidence that good correction and pain free motion can be obtained. PMID- 2231357 TI - Behavior of orthotic materials in chiropody. AB - The author provides insight into the functioning of materials used in shoe inserts. This study could be the basis for criteria with which to appraise materials that are in use today, and also to properly evaluate new materials before clinical trials. PMID- 2231356 TI - Epidemic and classic Kaposi's sarcoma of the feet. A comparative study. AB - The clinical behavior of Kaposi's sarcoma involving the feet is compared for patients with and without AIDS. Although AIDS-related Kaposi's sarcoma is less likely to be confined to the legs than is non-AIDS-related Kaposi's sarcoma, the legs are the most common site of disease in both forms. Kaposi's sarcoma occurring in the AIDS setting is as radiosensitive as that which occurs in the patient without AIDS. Palliative radiotherapy can offer substantial relief for affected patients. PMID- 2231358 TI - Subchondral bone cysts of the phalanges. AB - Subchondral phalangeal bone cysts frequently are encountered when reviewing foot x-rays. Radiologically, these lesions appear as a focus of subchondral radiolucency surrounded by a rim of sclerotic bone. Radiologic and histologic examinations demonstrate that these lesions are identical to the subchondral bone cysts associated with osteoarthritis of the hip and the more recently described cysts of the hallucal sesamoids and the head of the first metatarsal. PMID- 2231359 TI - Treatment of verrucae via radio wave surgery. AB - Verrucae are common skin lesions seen mainly in younger patients. They often are seen on the plantar surface of the foot. Many different types of treatments have been used over the years, with varying levels of success. The authors present a thorough review of previous treatments and present a new and effective method of surgical excision using radio wave technique. The success of this treatment is high, and the postsurgical pain and complication level is minimal. PMID- 2231360 TI - Stress fracture of the tarsal middle cuneiform bone. A case report. AB - The authors have presented what they believe is the only reported case of a stress fracture of the tarsal middle cuneiform bone. Stress fracture pathogenesis, as well as diagnosis and treatment, were reviewed. It has been proposed that the middle cuneiform may be subject to increased stress in the runner during the propulsive phase, as this is the midfoot bone that transmits weight proximally in the medial column. This is evident by studying the cancellous structure of the tarsal bones. The ligamentous and osseous architecture of this region also can produce a midfoot buckling when the foot is plantarflexed against resistance. Prompt diagnosis and treatment is the key in preventing the stress fracture from becoming a chronic source of discomfort. PMID- 2231361 TI - Fibroepithelial polyps. An unusual case report. AB - Fibroepithelial polyps usually present as small, benign dermal growths known as skin tags. The incidence of this lesion in the foot has not been precisely determined. An unusual case and a literature review were presented. PMID- 2231362 TI - Correction of hallux varus via split tendon transfer. AB - The split tendon transfer is introduced as an additional procedure for the correction of hallux varus. More clinical and statistical evaluations are required to fully appreciate its potential benefits. PMID- 2231363 TI - Cutaneous angiosarcoma. A literature review and case report. AB - A case of angiosarcoma of the lower extremity was presented. This rare but highly malignant soft tissue tumor usually presents as a raised pigmented lesion. Wide surgical excision or amputation is the treatment of choice. Radiotherapy may offer some relief in cases that are inoperable. PMID- 2231364 TI - Research process. An overview. AB - It has been suggested that podiatric education, training, and practice too often are not well understood outside of the profession. If this is the case, a potential remedy is for more podiatric health professionals to publish work that has significance. Beginning with this article and continuing through a total of six articles, the research process is used as a paradigm for enhancing podiatric literature in the future. PMID- 2231365 TI - Predicting hallux abducto valgus. PMID- 2231367 TI - Advances in intraocular lens biomechanics. PMID- 2231366 TI - Human immunodeficiency virus. PMID- 2231368 TI - Measurement of elastic resisting forces of intraocular haptic loops of varying geometrical designs and material composition. AB - The relationship between experimentally induced intraocular lens (IOL) haptic deformation and resulting elastic haptic counter-resisting forces measured by electronic dynamometry was examined for 34 different IOL haptics of varying material composition and geometrical designs. Poly(methyl methacrylate) (PMMA) and polypropylene loops of similar geometry did not fundamentally differ from one another, although lenses of differing geometry behaved differently. Unlike PMMA and polypropylene loops, soft haptics of poly-HEMA and silicone rubber demonstrated a larger elastic resistance force to the same degree of deformation. This was based upon design characteristics of the lenses and not upon intrinsic properties of the materials, which would have produced the opposite result. By comparative analysis of these dynamometer measurements and considerations of the lens design and elastic properties (including memory) of the component materials, we can calculate the stresses upon the zonular and capsular bag structures during and after IOL implantation. PMID- 2231369 TI - Multilamellar hydrodissection in phacoemulsification and planned extracapsular surgery. AB - Multilamellar hydrodissection is the injection of balanced salt solution into multiple lamellae of the lens, cleaving it into a small nucleus and multiple layers of cortex. In phacoemulsification, the smaller nucleus reduces phacoemulsification time, and the thicker bed of cortex provides greater protection for the posterior capsule. In extracapsular extraction, the smaller nucleus can be more readily extracted, which is particularly advantageous when capsulorhexis is performed. Creation of multiple cortical lamellae facilitates their aspiration, either with the phacoemulsification or irrigation/aspiration tips. Multilamellar hydrodissection increases the predictability and safety of phacoemulsification and planned extracapsular cataract extraction. PMID- 2231370 TI - Displacement of bag-placed hydrogel lenses into the vitreous following neodymium: YAG laser capsulotomy. AB - We report two cases in which hydrogel lens implants have dislocated posteriorly into the vitreous body following YAG laser capsulotomy. These lenses were placed in the bag in conjunction with a capsulorhexis. A comparison with our results using silicone and poly(methyl methacrylate) implants indicates that this phenomenon has occurred only with hydrogel implants. Analysis of the various parameters associated with the laser capsulotomy procedure suggests that the overall length and design of the hydrogel implants were key factors. Because of the severity of this complication, we have discontinued the use of this type of implant. PMID- 2231371 TI - Evaluation of 150 consecutive cases of poly HEMA posterior chamber lenses implanted in the bag using a small-incision technique. AB - We report the results of 150 capsular bag implantations of the IOGEL PC-12 hydrogel lens. Mean follow-up was seven months. Following capsulorhexis and phacoemulsification, a Faulkner folder was used to insert the lens through a 3.5 mm to 4.0 mm scleral tunnel incision. Initially, a number of surgical complications were encountered. Because of increasing experience and modified instrumentation and technique, these did not occur in the later cases. Visual results were good, all eyes gaining a best case visual acuity of 20/40 or better and 97% achieving 20/25 or better. Morphological results were satisfactory. Generally the lenses remained centered and at a distance from the iris. Retention of viscoelastic substance or debris between the lens and the posterior capsule, occasionally observed at the start of the series, has been avoided by retrolental aspiration. Persistent pigment dispersion, which was observed when the lens had been implanted in the sulcus, was not seen. Tolerance of the lens material was generally satisfactory. There were six cases (4%) of fibrinoid uveitis, which is a relatively high incidence. From our experience and results we conclude that this implantation procedure allowed controlled insertion and placement of the IOGEL lens, provided that adequate instrumentation and technique was used; visual performance was comparable to that of poly(methyl methacrylate) lenses; capsular bag fixation furnished satisfactory morphological results, provided an adequately shaped capsulorhexis was performed. PMID- 2231372 TI - Early results with the 8 mm and 9 mm HEMA disc intraocular lens. AB - This study presents our experience with 34 HEMA disc intraocular lenses implanted in the capsular bag. Despite the small number of cases and the relatively short mean postoperative follow-up of nine months, the results show a low incidence of uveitis and capsular fibrosis and excellent biocompatibility. The following complications were observed: four luxations of the 8 mm lens and one of the 9 mm lens in the anterior chamber. A visual acuity of 20/20 to 20/40 was obtained in 32 patients (94%). PMID- 2231373 TI - Capsular bag fixation of one-piece silicone lenses. AB - One hundred sixteen (116) one-piece silicone implants (STAAR 4203C) designed for capsular bag placement have been implanted since July 1987 and followed for up to two years. It appears that the posterior capsular opacification rate is significantly less than with sulcus-fixated one-piece silicone implants. This has been achieved by incorporating the small round capsulotomy using the capsulorhexis technique in addition to a modified endocapsular phacoemulsification technique. The percentage of posterior capsules requiring neodymium:YAG laser treatment in the first four months was 4.3 for the 4203C silicone IOLs and 20.0 for the sulcus-fixated one-piece silicone IOLs. The opacification rates for the one-year follow-up were 11% and 31%, respectively. PMID- 2231374 TI - Prediction of postoperative intraocular lens chamber depth. AB - The postoperative intraocular lens (IOL) chamber depth was predicted using a multiple linear regression analysis of the postoperative chamber depth as a function of the corneal height, the preoperative chamber depth, and the axial length in 279 patients with a posterior chamber lens implant. Based on a linear regression formula incorporating these preoperatively defined parameters, the postoperative IOL chamber depth could be predicted with a correlation coefficient of 0.71 and an error of +/- 0.30 mm (SD). It is concluded that an individual prediction of the IOL chamber depth will improve the accuracy in IOL calculation. PMID- 2231375 TI - Preoperative astigmatic influence on the predictability of intraocular lens power calculation. AB - The preoperative and postoperative influence of different parameters on the predictability of formulas used for intraocular lens (IOL) power calculation (axial length, corneal dioptric power, IOL malposition, postoperative astigmatism) has been shown by various authors. In this study, we evaluated the preoperative astigmatic influence on the prediction of postoperative refraction in eyes operated on for cataract with IOL implantation. Three hundred and fifty nine eyes were evaluated after cataract surgery and IOL implantation. We calculated predictive errors of both the Binkhorst and SRK formulas for each eye. Based on the outcome of the predictive errors we divided the eyes into six groups: three of high and three of low predictability. Preoperative astigmatism in these groups was statistically compared (using the Student's t-test). The preoperative astigmatism was always higher in the group with low predictability than in the group with high predictability (P less than .05). PMID- 2231376 TI - Comparison of the protective effects of methylcellulose and sodium hyaluronate on corneal swelling following phacoemulsification of senile cataracts. AB - The protective effects of two viscoelastic substances (hydroxypropyl methylcellulose and sodium hyaluronate) on the cornea during phacoemulsification of senile cataracts were investigated in a prospective, randomized, clinical study. The viscoelastic substances were placed in the anterior chamber before and during phacoemulsification. The mean increase in central corneal thickness (measured by ultrasonic pachymetry) on the first postoperative day was statistically significantly higher (P less than .05) in the methylcellulose group (35 eyes) than in the sodium hyaluronate group (35 eyes). Five weeks postoperatively the difference in mean central corneal thickness between the two groups was not statistically significant. However, one eye in the methylcellulose group developed bullous keratopathy. The present study indicates that methylcellulose does not protect the corneal endothelium as effectively as sodium hyaluronate during phacoemulsification procedures. PMID- 2231377 TI - Air bubble endothelial damage during phacoemulsification in human eye bank eyes: the protective effects of Healon and Viscoat. AB - Following insertion of either Healon (sodium hyaluronate) or Viscoat (sodium chondroitin sulfate-sodium hyaluronate) into the anterior chamber of human eye bank eyes, a controlled amount of small air bubbles was introduced into the anterior chamber during phacoemulsification. After vital staining, damage to endothelial cells in the central cornea was quantified. Endothelial damage averaged 4.5% in eyes in which no viscoelastic was used (positive control), whereas damage was only 0.4% (P less than .001) in eyes in which a viscoelastic was inserted but no air bubbles were introduced (negative control). Endothelial damage in test specimens using air plus Healon averaged 4.9%. Damage in test specimens using air plus Viscoat averaged 0.3% (P less than .02). As demonstrated by scanning electron microscopy, many areas in the positive controls and in the Healon test specimens were damaged too extensively to quantitate accurately by the method we used. Thus, Viscoat may prevent or lessen damage to the corneal endothelium by small air bubbles during phacoemulsification. PMID- 2231378 TI - Comprehensive study of damage to intraocular lenses by single and multiple nanosecond neodymium: YAG laser pulses. AB - The results of an extensive study of the probability of damage induced in implant quality intraocular lenses (IOLs) by a commercially available nanosecond Nd:YAG photodisruptor are presented. These results were compared with the morphology of damage seen on scanning electron microscopy. The differences in the shape of the damage probability curves derived for the different lens groups demonstrate that a single threshold value does not characterize the threshold for IOL damage. We suggest that a standard method using a clinical photodisruptor be used by all workers to derive these curves for all IOLs in clinical use. The clinical relevance of our findings is emphasized. PMID- 2231379 TI - New refractive method for laser thermal keratoplasty with the Co:MgF2 laser. AB - We have observed corneal curvature changes from laser thermal keratoplasty with a Co:MgF2 laser. We studied corneal curvature changes in rabbits and have identified specific treatment patterns and laser parameters that can correct myopia and astigmatism. These corneal changes, some as large as 8 diopters, have been stable for at least one year, and slitlamp examination demonstrates clear central corneas with normal appearance. PMID- 2231380 TI - Preliminary study of argon fluoride (193 nm) excimer laser trabeculectomy. Scanning electron microscopy at five months. AB - There is an increasing interest in the use of the excimer laser in ophthalmology, particularly in refractive surgery. The argon fluoride (193 nm) excimer laser ablates tissue with a high degree of precision and without any mechanical or thermal damage to surrounding structures. In this study, the argon fluoride excimer laser was experimentally used in the rabbit model to perform a trabeculectomy. Clinical and scanning electron microscopic evaluations showed a successful and patent filtering procedure. At the five-month follow-up the trabeculectomy was smooth and regular and there was no evidence of inflammation or thermal damage on the surrounding structures. PMID- 2231381 TI - Intraocular lens implantation in developing countries. AB - One of the chief aims of ophthalmic workers in developing countries is to operate on as many cataract patients as possible in the most cost-efficient manner. Therefore, our intraocular lens (IOL) implantation policy in Nakuru and Kikuyu, Kenya, is to reserve IOLs for monocular cataract patients of all ages, who otherwise would not have use of the aphakic eye. In this study, we review 105 of our first IOL implantations. In 60%, the uncorrected postoperative visual acuity was 20/60 or better. PMID- 2231382 TI - Practice styles and preferences of ASCRS members--1989 survey. AB - A survey of the practice styles and preferences of 1989 ASCRS members with a U.S. zip code was performed in September 1989. More than 3,700 questionnaires were mailed and over 42% (1,543) were returned prior to the cut-off date. Three main profile questions were used to cross-analyze the results: the age of the ophthalmologist, the volume of cataract surgery per month, and the geographic location. This report also compared the data with previously published surveys of the ASCRS membership. PMID- 2231383 TI - Severe fibrinous reaction after cataract and intraocular lens implantation surgery requiring neodymium:YAG laser therapy. AB - Fibrous membrane formation on the anterior surface of an intraocular lens with occlusion of the pupil was noted in five patients having phacoemulsification and one patient having planned extracapsular cataract extraction. Initial onset of pain and decreased vision ranged from eight to 36 postoperative days. Since these patients did not respond fully to steroid therapy, the neodymium:YAG laser was used to disrupt the fibrinous membrane which occluded the pupil. In all but one case, the fibrinous reaction responded to laser therapy. Generally, less energy was required when laser therapy was initiated early in the treatment plan. PMID- 2231384 TI - New posterior chamber lens with open circular haptic for a small capsular opening: preliminary report. AB - This report describes a single-piece poly-(methyl methacrylate) posterior chamber lens for implantation through a small capsular opening. It has open circular loops with an eyelet at each loop end. The optic is 6 mm in diameter and the overall diameter of the intraocular lens (IOL) is 11 mm. The lens diameter can be reduced to 7 mm by grasping the eyelets at both open loop ends with a specially designed holding forceps. The IOL is inserted in the capsular bag after circular capsulorhexis or through a linear capsulotomy in the intercapsular technique. This IOL is adaptable to a small capsular opening and maintains the usual shape of the capsular bag, similar to a disc lens. PMID- 2231385 TI - Specular microscopic observation of eye-bank corneal endothelium using the clinical specular microscope. AB - A special holder for endothelial evaluation of eye-bank corneas using the clinical specular microscope was developed. Using this holder, pictures of the corneal endothelium can be taken without the eye-bank specular microscope. PMID- 2231386 TI - One-handed method of posterior chamber phacoemulsification. AB - An alternative method of posterior chamber phacoemulsification is presented. This method is one-handed, uses a 30-degree tip, and emulsifies the nuclear rim in a circumferential manner. PMID- 2231387 TI - Scleral pocket incision applied to insertion of the nut and bolt keratoprosthesis. PMID- 2231388 TI - Viscoat aspiration with an enlarged Simcoe cannula. PMID- 2231389 TI - Consultation section. Blunt trauma to the eye. PMID- 2231390 TI - [Autografts and tooth transplants. Operative indications]. AB - In order to evaluate the prognosis in tooth transplant procedure the literature on this subject was reviewed. The survival of the periodontal ligament is necessary to prevent ankylosis and root resorption. In order to obtain optimal clinical results, the following guidelines are proposed: preparation of the recipient site 2 weeks prior to graft placement, preservation of intact Pdl at time of extraction, rapid reimplantation of tooth in new socket, short term contention (2-3 weeks); endodontic therapy 8-10 weeks after tooth transplantation. PMID- 2231391 TI - [Clinical research on the etiopathology of gingival recession]. AB - Frequency severity of gingival recessions was studied with Stahl and Morris indices. The results showed that the localization of gingival recession was more important on the mandible (37%) than on the maxillary (27.6%) it, also demonstrated the importance of various etiologies and particularly the association of trauma - tooth malposition (81%). PMID- 2231393 TI - [Role of Kiel bone in periodontal surgery. Report of a case]. AB - A case in which an infrabony pocket was treated with Kiel bone is presented. The healing of the lesion was assessed by reentry 9 months after the procedure was completed. PMID- 2231394 TI - [Comparative efficiency of 3 experimental ultrasonic instruments in vivo]. AB - A clinical study was performed to compare the in vivo effectiveness of three different instruments for calculus removal. The instruments were Odontoson, Cavitron and Siroson. Following scaling of the roots, the teeth were extracted, stained and assessed for remaining calcareous deposits. Comparative statistical analysis revealed no significant differences among the three methologies. PMID- 2231392 TI - [Preprosthetic periodontal examination. Clinical observations]. AB - A detailed and comprehensive clinical examination is an important and fundamental basis for establishing a proper diagnosis for prosthetic treatment. It is important to make an accurate diagnosis, a rational treatment plan and establishing a prognosis. A careful examination of teeth and periodontium must be done and the prosthetic plan must consider the periodontal status of the teeth. The prosthetic treatment plan must take into consideration problems of appliance retention, iatrogenic tooth injuries and other factors. A classification based on 6 different clinical situations suggested and their therapeutic solution proposed. PMID- 2231395 TI - [Prevalence of juvenile periodontitis in Ille-et-Vilaine. Study of an orthodontic population]. AB - The incidence of Juvenile Periodontitis was studied in 1600 patients residing in Ille et Vilaine, France. The diagnosis was established by the use of panoramic radiography on orthodontic patients. Among this population of patients only 3 cases of Juvenile Periodontitis were found. This incidence of 0.187% is similar to that found in other industrialized countries. PMID- 2231396 TI - [Treatment of a vestibular gingival papilloma: report of a case]. AB - A 14 years old patient showed a vestibula papilloma. The lesion and the treatment are described. This inflammatory etiology is confirmed by the histologic features of the biopsy. PMID- 2231397 TI - The control of limb geometry in cat posture. AB - 1. The aim of this study is to address the problem of the controlled variable in quadrupedal stance. In particular, we considered whether the projection of the centre of mass of the body on the support surface or the joint torques or the geometrical configuration of the limbs are primarily controlled. 2. Cats were trained to stand freely on a platform which could be tilted in the sagittal plane by up to +/- 20 deg. The normal and tangential components of the contact forces at each paw were measured by means of load cells. The position of limb joints was recorded by means of the ELITE system. 3. The projection of the centre of body mass on the platform, as well as the orientation and length of limb axes, varied to only a limited extent with tilt angle. In particular, the limb axes were closely lined up with the vertical, as were the vectors of the contact forces at the paws. As a result, the torques at the proximal joints (scapula and hip) were close to zero and the torques at the other joints varied little with table tilt. 4. In order to test the different hypotheses on postural control, an external load (10-20% of the animal weight) was applied to the cat forequarters. The projected centre of mass consistently shifted forwards, contrary to the hypothesis that this parameter is controlled in stance. Instead, the geometry of limb posture remained unmodified after load application, even though the torques at forelimb joints were much greater than in the control. 5. This postural behaviour showed no sign of adaptation over a period of 24 h of continuous load application. 6. It is concluded that limb geometry is primarily controlled in stance. The results are discussed in the context of current notions on hierarchical control and body scheme. PMID- 2231399 TI - Response behaviour of cat dorsal horn neurones receiving input from skeletal muscle and other deep somatic tissues. AB - 1. In chloralose-anaesthetized cats, lumbosacral dorsal horn neurones driven by receptors in skeletal muscle and other deep tissues (tendon, joint, bone) were studied. 2. Upon mechanical stimulation two main types of neurones were found: units having exclusive input from deep tissues (D cells, 28.8%) and units with input from both cutaneous (C) and deep (D) receptors (C-D cells, 71.2%). In both categories, low-threshold mechanosensitive (LTM) and high-threshold mechanosensitive (HTM) elements were present. 3. Neurones responding exclusively to noxious stimulation of skeletal muscle were not found; the input from muscle nociceptors converged on the dorsal horn cells together with other deep or cutaneous input. D cells with exclusively HTM input were numerous; these could from the anatomical basis for a specific spinal pathway for deep pain. 4. For C-D neurones with input from deep nociceptors the cutaneous receptive field (RF) was usually located distal to the deep one. This arrangement might be of relevance for the occurrence of hyperaesthetic skin distal to painful deep lesions. 5. Cold block of the spinal cord resulted in a marked increase in the neurones' mechanical responsiveness and in the number of RFs per neurone. Simultaneously, the proportion of HTM RFs increased, particularly in cells with input from skeletal muscle. 6. The recording sites in the dorsal horn were located in the superficial dorsal horn and in and around laminae V/VI. Evidence is presented that in dorsal horn cells with deep input not only the mechanical excitability but also the degree of convergence is controlled by descending spinal pathways. PMID- 2231398 TI - Low-threshold mechanoreceptive and nociceptive units with unmyelinated (C) fibres in the human supraorbital nerve. AB - 1. In recordings from the human supraorbital nerve with tungsten microelectrodes, eleven afferent units with unmyelinated (C) axons were identified on the basis of their conduction velocities (0.6-1.4 m/s). 2. Eight units had low mechanical thresholds (less than or equal to 0.23 g) and could be activated up to their maximal firing rates of about 100 impulses/s by weak tactile stimuli, whereas three units had higher thresholds (5.5 g) and responded vigorously to noxious stimuli only. 3. During a skin indentation the low-threshold units adapted to an irregular low-frequency discharge, and release of the stimulus elicited a prominent off-response often ending with an after-discharge. Slow stroking was a particularly effective stimulus, even when done with cotton wool, whereas rapid stroking reduced the response. All types of stroking stimuli were occasionally followed by after-discharges. Repeated mechanical stimulation at short intervals resulted in a decline of the response, indicating receptor fatigue. For two units a response to skin cooling was observed. 4. The above low-threshold C units have all the main characteristics of the C mechanoreceptors known from the cat and primates but not previously proven to exist in man. The high-threshold C units are similar to the polymodal nociceptors found in other human skin areas. PMID- 2231400 TI - Developmental changes in the half-life of acetylcholine receptors in the myotomal muscle of Xenopus laevis. AB - 1. Tail preparations, containing myotomal muscle and associated spinal cord, were isolated from embryos and tadpoles of Xenopus laevis between stages 25 and 49 (1.15-12 days) and were pulse-labelled with 125I-alpha-bungarotoxin (125I alpha BT) so that the half-life (T1/2) of their acetylcholine receptors (AChRs) could be estimated in organ culture. 2. For the entire population of AChRs, estimates of T1/2 based on a single exponential decline in radioactivity (but see item 4 below) increased from 53-55 h at stages 25-31 (1.15-1.56 days) to approximately 135 h at stage 47 (5.5 days). Beyond stage 47 T1/2 increased only slightly. 3. Radioautographic estimates of the T1/2 of extrajunctional AChRs at stages 47-48 (5.5-7.5 days) were 41-50 h. It follows that the developmental change in the T1/2 of the entire population of AChRs was due to the junctional AChRs. 4. At stages 47-49 (5.5-12 days) the decline in radioactivity for the entire population of AChRs was fitted well by a double exponential. Assuming a T1/2 of 50 h for the extrajunctional AChRs and 210 h for the junctional AChRs, the correlation coefficient (r) was 0.9947 +/- 0.0014 (mean +/- S.E.M.; n = 14) and junctional AChRs were estimated to comprise 80 +/- 3% of the entire population. Similar analysis, as well as experiments in which the degradation of junctional AChRs was assessed by pulse-labelling with fluorescent alpha-bungarotoxin, suggested that at earlier stages of development the junctional AChRs have a shorter T1/2 and comprise a smaller fraction of the entire population. 5. The developmental increase in T1/2 occurred even when animals were raised in the anaesthetic tricaine or in tetrodotoxin, conditions which abolished all motor activity. 6. Developmental increases in T1/2 also occurred in culture but were smaller than those in vivo. The increases in culture did not occur amongst those AChRs which were pre-labelled with 125I alpha BT. 7. It is concluded that in Xenopus myotomal muscle the T1/2 of junctional AChRs begins to increase within a day after the onset of innervation and that the increase does not require nerve or muscle impulse activity. We suggest, among other possibilities, that it may depend upon incorporation of a different molecular species of AChR into the postsynaptic membrane. PMID- 2231401 TI - Brown adipose tissue thermogenic responses of rats induced by central stimulation: effect of age and cold acclimation. AB - 1. Urethane-anaesthetized, age-matched cold-(4 degrees C) and room (21 degrees C) acclimated groups of Sprague-Dawley rats were given repeated (three) ventromedial hypothalamic electrical stimulations. Interscapular brown adipose tissue (IBAT), colonic, surface tail temperatures and blood pressure were monitored before and after each electrical stimulation. Propranolol HCl (2.5 mg kg-1 i.v.) was given 10 min prior to the last (third) ventromedial hypothalamic stimulation. 2. Repeated electrical stimulation of the ventromedial hypothalamic (VMH) nucleus to either small or large rats (kept at 21 degrees C) caused no significant change in interscapular brown fat, colonic or surface temperatures compared to respective pre-stimulation control values whereas mean arterial pressure was slightly but significantly increased during the 30 s stimulation period. 3. Electrical stimulation of the ventromedial hypothalamic nucleus of small or large rats, kept at 4 degrees C for 3 weeks prior to testing, caused significant (greater than 0.25 and greater than 0.40 degrees C, respectively) rises in interscapular BAT temperature from respective prestimulation control values. Colonic temperatures increased following ventromedial hypothalamic electrical stimulation only in the small, 4 degrees C-acclimated group whereas surface tail temperatures did not significantly change after stimulation of either cold-exposed group. Mean arterial pressures were significantly increased during ventromedial hypothalamic electrical stimulation in both 4 degrees C-acclimated groups, compared to pre stimulation control levels and, in addition, were above those of age-matched rats kept at 21 degrees C. Intravenous propranolol, which decreased interscapular brown fat and colonic temperatures in all groups, blocked the rise in interscapular brown fat and colonic temperatures of the 4 degrees C-acclimated rats following the last electrical stimulation of the ventromedial hypothalamic nucleus. 4. In vitro biochemical analysis of the interscapular brown fat pads of another four groups of age-matched, small and large 21 and 4 degrees C-acclimated rats revealed that the thermogenic capacity of the 4 degrees C-acclimated groups was, in all cases, significantly increased from age-matched groups previously kept at 21 degrees C, as shown by significant increases in brown adipose tissue mass, BAT DNA and protein content, BAT mitochondrial protein and BAT mitochondrial GDP binding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231402 TI - Effects of systemic hypoxia on the distribution of cardiac output in the rat. AB - 1. Studies were made in unanaesthetized rats of cardiovascular responses induced during 3 min periods of systemic hypoxia (inspirate 8 or 6% O2). Arterial pressure and heart rate were recorded continuously; cardiac index and regional blood flows were measured in normoxia and at the 2nd min of hypoxia by injection of radiolabelled microspheres. Comparisons are made with changes recorded in Saffan-anaesthetized rats during 8% O2 using microspheres and in previous studies using electromagnetic transducers on renal, mesenteric and femoral arteries (Marshall & Metcalfe, 1988a). 2. In unanaesthetized rats, the initial 1-1.5 min of hypoxia evoked behavioural arousal associated with a short-lasting rise in arterial pressure and heart rate. This agrees with our previous proposal that hypoxia activates the brain stem defence areas by stimulating peripheral chemoreceptors. 3. In unanaesthetized rats, these changes were superimposed upon a gradual fall in arterial pressure and tachycardia, the responses being greater during 6 than 8% O2 (cf. Saffan-anaesthetized rats). Further, in all rats at the 2nd min of hypoxia, cardiac index and vascular conductance of most body tissues was increased. It is concluded that the fall in arterial pressure is due to peripheral vasodilatation. 4. In the unanaesthetized rats, the tendency for vascular conductance in kidney, intestine and gastrocnemius muscle to increase (more during 6 than 8% O2) allowed increases in blood flow in the last two regions. These changes accord with those recorded under Saffan anaesthesia. 5. In both unanaesthetized and anaesthetized rats, hypoxia induced pronounced increases in vascular conductance of diaphragm, adrenal gland, cerebral hemispheres, cerebellum and brain stem, the resultant increases in blood flow being larger in the unanaesthetized rats. 6. It is proposed that in unanaesthetized, as in anaesthetized, rats the regional dilator responses predominantly reflect the local dilator effects of tissue hypoxia. Possible dilator factors are considered. PMID- 2231403 TI - Respiratory-related discharge pattern of sympathetic nerve activity in the spontaneously hypertensive rat. AB - 1. Synchronization of spontaneous sympathetic discharge during the respiratory cycle was studied in the cervical and renal nerves of vagotomized, normotensive Wistar-Kyoto rats (WKYs) and age-matched spontaneously hypertensive rats (SHRs). Phrenic nerve discharge was used as an index of central inspiratory activity. 2. In normotensive Wistar-Kyoto rats depression of sympathetic activity appeared at the onset of inspiration reaching a minimum at mid-inspiration. Peak maximal sympathetic discharge corresponded to postinspiratory phase; a second increase sometimes appeared in late expiration. Variations of respiratory frequency over wide range of experimental conditions by hypoxia, hyperoxia, hyper- or hypocapnia and transection of carotid sinus nerves did not affect this pattern. 3. In SHRs the respiratory-phase-related timing of sympathetic discharge was variable. In normoxia, the maximal sympathetic activity occurred in late inspiration, preceded by short depression at early inspiration and followed by postinspiratory depression. A second increase in sympathetic activity was observed in mid expiration. 4. The pattern of respiratory phase modulated sympathetic activity in SHRs was altered by hypoxic stimulation of the peripheral chemoreceptors. The early inspiratory depression of sympathetic activity was substantially prolonged and the maximal sympathetic discharge was shifted from inspiration to early expiration. This effect was abolished after carotid sinus nerves had been cut. 5. Hypercapnic stimulation of central chemoreceptors in SHRs with carotid sinus nerves cut did not influence the timing of the sympathetic activity in relation to the respiratory phase, though the magnitude of rhythmical sympathetic discharges was increased. 6. We discuss the possibility that altered synchronization between central respiratory drive and sympathetic neuronal system may contribute to the neurogenic mechanisms of arterial hypertension in SHRs. PMID- 2231404 TI - Human placental L-tyrosine transport: a comparison of brush-border and basal membrane vesicles. AB - 1. The mechanisms responsible for L-tyrosine transport at both the maternal facing and fetal-facing surfaces of the human full-term placenta have been studied using isolated brush-border and basal membrane vesicles under conditions where a direct comparison of the transport properties of the two membranes can be made. 2. Brush-border vesicle uptake of L-tyrosine was substantially into an osmotically active space. Transport was Na(+)-independent, N-ethylmaleimide sensitive (half-maximal inhibition, Ki = 1.1 mM), and insensitive to pH over the range 5.5-8.5. The initial rate of brush-border L-tyrosine uptake as a function of concentration showed saturation and obeyed Michaelis-Menten kinetics with Michaelis constant (Km) and maximum velocity (Vmax) values of 54.2 microM and 1.28 pmol (mg protein)-1 s-1, respectively. Influx of L-tyrosine was stereospecific and was virtually completely abolished by L-phenylalanine, L tryptophan, L-leucine or by 2-aminobicycloheptane-2-carboxylic acid. These properties suggest that system L is responsible for brush-border L-tyrosine transport. 3. Basal membrane transport of L-tyrosine was more complex and uptake was slower than that found in the brush border. Although, as in the brush-border membranes, uptake was completely Na(+)-independent, N-ethylmaleimide was a less effective inhibitor, there was stimulation of transport at more alkaline pH and uptake did not show marked stereospecificity. An apparent Km of 168.9 microM and a Vmax of 0.31 pmol (mg protein)-1 s-1 were calculated for basal L-tyrosine transport. There was clear inhibition by L- and D-tyrosine, L-phenylalanine and L tryptophan. 2-Aminobicycloheptane-2-carboxylic acid was not as effective. 4. These findings suggest the existence of non-identical carrier-mediated transport systems for L-tyrosine in brush-border and basal membranes. Brush-border transport resembles that by system L; L-tyrosine transport at the basal membrane may be via system t. PMID- 2231406 TI - Dynamics and dimensions of cardiac output changes in humans at the onset and at the end of moderate rhythmic exercise. AB - 1. An improved Doppler ultrasound technique was used to measure stroke volume (SV) and cardiac output (CO) on a beat-to-beat basis in a group of supine humans before, during and after periods of standardized, rhythmic exercise, involving the quadriceps muscle groups on both sides. The development of CO on such bouts of exercise was compared to Doppler ultrasound records of the simultaneous femoral arterial flow (FF) response. 2. Records of CO at rest revealed spontaneous fluctuations around a mean level, with differences between the minimal and maximal values of the order of 1 l min-1. The mean CO level at rest again varied considerably from one day to another and from test run to test run. 3. Upon start of exercise an immediate and rapid increase in heart rate (HR) and CO took place. The entire increase, the size of which varied appreciably from test run to test run, was completed within 10-15 s. No or only minor changes were seen in the mean SV level during the exercise periods. 4. The time course of the increase in FF was indistinguishable from that of the increase in CO, which occurred without any detectable delay relative to the changes in FF. These closely parallel developments indicate a tight regulatory coupling between the two types of flow changes. 5. In the majority of tests the total and two-sided increase in FF seen in the steady-state situation in the last part of an exercise period was significantly larger than the recorded increase in CO. This discrepancy implies that some redistribution of flow from tissues other than the working muscles might take place, even at this moderate level of work. 6. Upon the end of exercise a striking but transient increase in CO occurred, resulting from an increase in SV concomitant with a maintained HR. In the course of five to eight post-exercise cardiac cycles about 100 extra milliliters of blood were expelled from the heart. This cardiac outflow overshoot was found to occur during a post-exercise fall in mean arterial blood pressure (MAP). PMID- 2231405 TI - Synchronization of motor units in human masseter during a prolonged isometric contraction. AB - 1. The action potentials of concurrently active motor units in human masseter were recorded on several fine-wire intramuscular electrodes and synchronization was assessed by cross-correlation of their firing times. 2. Long recording sessions and a test of significance for peaks in histograms were used to enhance detection of synchrony. 3. Synchrony in masseter units was found to be very weak, and was observed consistently only in histograms with a large number of counts. However, synchrony was widespread within the motoneurone pool; of the unit pairs whose cross-correlation histograms contained more than 100 counts per 1 ms bin, 89% were significantly synchronized. 4. The strength of synchrony between pairs of units did not change consistently during 15 min of continuous activity. 5. It was concluded that most, if not all, low-threshold masseter motoneurones have some common synaptic inputs, although the origin of those inputs remains unclear. PMID- 2231407 TI - Electrophysiology of glutamate and sodium co-transport in a glial cell of the salamander retina. AB - 1. Muller cells were isolated from salamander retinas and their membrane voltage was controlled with a whole-cell voltage clamp. External D-aspartate, L-aspartate and L-glutamate each induced a membrane current. D-Glutamate, kainate, quisqualate and N-methyl-D-aspartate were more than 100x less effective than L aspartate. Kynurenic acid had no effect on the current produced by L-glutamate, L aspartate or D-aspartate. 2. The current induced by an acidic amino acid (AAA) was completely dependent on the presence of external Na+. Neither Li+, Cs+, choline nor TEA+ were able to substitute for Na+. The relationship between external Na+ concentration and current amplitude can be explained if the binding of three Na+ ions enabled transport. The apparent affinity constant for Na+ binding was 41 mM. Altering K+, H+ and Cl- concentrations demonstrated that these ions are not required for transport. 3. The shape of the current-voltage relation did not depend on the external amino acid concentration. The relationship between D-aspartate concentration and current amplitude can be described by the binding of D-aspartate to a single site with an apparent affinity constant of 20 microM. 4. Influx and efflux of AAA were not symmetric. Although influx was electrogenic, efflux did not produce a current. Moreover, influx stimulated efflux; but efflux inhibited influx. 5. Removing external Na+ demonstrated that Na+ carried a current in the absence of an AAA. Li+ was a very poor substitute for Na+. This current may be due to the uncoupled movement of Na+ through the transporter. The relationship between the external Na+ concentration and the amplitude of the uncoupled current can be explained if the binding of two or three Na+ ions enabled the translocation of Na+ in the absence of an AAA. The apparent affinity constant for Na+ binding was approximately 90 mM. 6. The temperature dependence of the AAA-induced current had a Q10 between 8 and 18 degrees C of 1.95. The Q10 is consistent with a rate constant for influx of 10(4) s-1 (at -70 mV and 20 degrees C). The maximum rate of influx was measured following a concentration jump produced by the photolysis of 'caged' L-glutamate. The onset of the observed current was limited by the 1.3 ms resolution of the recording system. Hence, the rate constant for influx must be faster than 10(3) s-1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231408 TI - Strong Pasteur effect in rabbit corneal endothelium preserves fluid transport under anaerobic conditions. AB - 1. The hydration and transparency of the mammalian cornea are maintained by a metabolically dependent fluid transport system located in the endothelial cell layer. The purpose of the study was to determine whether this pump activity is dependent upon aerobic or anaerobic metabolism. 2. The ability of the cornea, superfused in vitro with a bicarbonate-Ringer solution containing glucose and adenosine, to maintain normal hydration (thickness) when respiration is inhibited has been examined in intact and de-epithelialized preparations and correlated with glycolytic activity and cellular concentrations of ATP. 3. In respiring intact and de-epithelialized corneas thickness was maintained for periods up to 5 h during superfusion with the control Ringer solution. 4. KCN (10(-3) M) or antimycin A (10(-6) M) caused the intact cornea to swell at 15 +/- 3 microns h-1, whereas the de-epithelialized tissue maintained normal thickness under these conditions. This swelling of the intact tissue appears to be due to the osmotic effect of increased epithelial lactate production under anaerobic conditions. 5. Pre-swollen de-epithelialized corneas deturgesced fully to original thickness at a rate of 43 +/- 7 microns h-1 under aerobic conditions, but with KCN or antimycin they deturgesced at only 65% of that rate and generally failed to return to their original thickness. 6. Ouabain (10(-4) M) caused de epithelialized corneas to swell in the presence of KCN or antimycin, as it did under aerobic conditions, showing that maintenance of hydration or deturgescence are pump-dependent processes under both conditions. 7. Lactate production was markedly stimulated by KCN or antimycin in intact and de-epithelialized preparations, but not in the stroma alone. The magnitude of the Pasteur effect was calculated to be 5-fold in the endothelium and 2.5-fold in the epithelium. Ouabain inhibited anaerobic lactate production in the endothelium by 50%. 8. ATP content of the epithelium following 5 h superfusion was 22.0 nmol cm-2 in control (aerobic) corneas, but fell to 1.9 nmol cm-2 in the presence of 10(-3) M-KCN, whereas the endothelial value fell only from 1.1 to 0.7 nmol cm-2 under these conditions. 9. Omission of glucose from the medium containing KCN or antimycin caused immediate swelling of tissues and a rapid decline of ATP content to less than 1% of that in control conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231410 TI - Reflex coronary vasodilation evoked by chemical stimulation of cardiac afferent vagal C fibres in dogs. AB - 1. Veratridine injected into the coronary circulation stimulates afferent vagal endings in the heart to evoke bradycardia and systemic hypotension (Bezold Jarisch reflex, coronary chemoreflex) and coronary vasodilation. We have examined certain features of the reflex coronary vasodilator response in anaesthetized dogs. 2. When the circumflex coronary artery was perfused at constant pressure (100 mmHg), injection of veratridine (0.3 micrograms kg-1) into the anterior descending artery decreased blood pressure and heart rate, and increased circumflex blood flow by 54%; when heart rate was kept constant, circumflex flow increased by 57%. The increase in circumflex flow was reduced 63% by atropine, and finally abolished by phentolamine. 3. During severe coronary underperfusion (perfusion pressure 45 mmHg), veratridine still increased coronary flow by 35%, an increase amounting to 24-64% of the coronary vascular reserve. Flow increased in all layers of the myocardium, but the relative distribution of flow between subendocardial and subepicardial layers was unaltered. 4. Veratridine stimulates both mechanosensitive and chemosensitive cardiac endings. Stimulating chemosensitive afferents selectively by injecting capsaicin (1.5 micrograms kg-1) into the anterior descending artery decreased blood pressure and heart rate, and increased circumflex flow by 50% (and by 36% when heart rate was kept constant). 5. In ten of fifteen dogs, veratridine and capsaicin still evoked coronary vasodilatation when vagal A fibres were blocked selectively by cooling to 7.5 degrees C, the increase in coronary flow averaging 45% of that at 37 degrees C. All responses were abolished by cooling to 0 degrees C. 6. We conclude that coronary vasodilatation can be evoked by selective stimulation of cardiac chemosensitive vagal C fibres, although the coronary vasodilation of the veratridine-induced Bezold-Jarisch reflex may be due to stimulation of both mechanosensitive and chemosensitive C fibres. We speculate that during periods of coronary underperfusion ischaemic stimulation of chemosensitive vagal C fibres evokes a reflex dilatation of the coronary vascular bed that supplements the dilatation dependent upon autoregulatory mechanisms. PMID- 2231409 TI - Permeability of frog mesenteric capillaries after partial pronase digestion of the endothelial glycocalyx. AB - 1. The proteolytic enzyme pronase, which degrades the endothelial cell glycocalyx, was perfused through single capillaries of frog mesentery. Hydraulic conductivity (Lp) of each vessel was determined before and after pronase perfusion. In three vessels in which Lp increased, the ultrastructure of interendothelial clefts was examined. In a separate group of frogs the effect of pronase on the endothelial glycocalyx was assessed by using cationized ferritin to label the capillary luminal surface. 2. Control Lp was 2.0 x 10(-7) cm s-1 cmH2O-1 (10 mg ml-1 bovine serum albumin, BSA, in frog Ringer solution). Vessels were then perfused with a solution containing 0.1 mg ml-1 pronase and 10 mg ml-1 BSA for 1 min. Lp measured in the same eleven vessels increased to 4.9 x 10(-7) cm s-1 cmH2O-1 (P less than 0.005). 3. Transverse sections of three of these vessels were examined by transmission electron microscopy at eight sites along each vessel. In these sections a total of 156 interendothelial cell clefts were found and photographed. No morphological features, such as fenestrations, transendothelial channels, or intercellular gaps associated with inflammation, were found which might account for the increases in Lp. 4. Measurement of cleft dimensions yielded a harmonic mean cleft depth (delta x) of 0.32 microns and an arithmetic mean cleft depth of 0.64 microns. Mean width (w) of the clefts outside the tight regions was 0.012 microns and the cleft length per unit area (L) was 1330 cm-1. The mean fractional pore area of vessel wall per unit cleft depth, Ap/delta x, calculated as Lw/delta x, was 48.7 cm-1. 5. There was less cationic ferritin (CF) labelling of the luminal glycocalyx in pronase-perfused than in control capillaries. On average, the proportion of the luminal surface covered by CF was 85% in controls and 42% in pronase-treated capillaries (P less than 0.01). In some vessels the CF pattern was greatly disrupted, indicating large changes in the glycocalyx structure. 6. It is concluded that the moderate increases in Lp induced by pronase perfusion are associated with partial digestion of the endothelial glycocalyx but are not accompanied by changes in the dimensions of the intercellular cleft. These observations support the fibre matrix hypothesis of capillary permeability and suggest that the endothelial glycocalyx contributes as much as 60% of the hydraulic resistance of the capillary wall. PMID- 2231412 TI - Resting calcium concentrations in isolated skeletal muscle fibres of dystrophic mice. AB - 1. Single, intact muscle fibres were dissociated enzymatically from skeletal muscles of phenotypically normal (+/?) and dystrophic mice (129/ReJ dy/dy: Dystrophia muscularis), and resting Ca2+ levels were measured by image analysis of intracellular Fura-2 fluorescence in distinct parts of the fibres. 2. Fura-2 was introduced into fibres by ionophoresis with glass microelectrodes to concentrations of between 50 and 200 microM. Over this concentration range there was no apparent buffering of intracellular Ca2+ by Fura-2. 3. Fibres isolated from the soleus, flexor digitorum brevis (FDB) and extensor digitorum longus (EDL) muscles of normal animals maintained resting [Ca2+] of 106 +/- 2 nM. Ca2+ distributions within individual fibres were homogeneous. 4. Fibres from dystrophic animals maintained [Ca2+] that was elevated two- to fourfold in comparison to normal fibres. 5. The population of skeletal fibres from dystrophic mice which displayed morphology similar to that of fibres of normal animals were found to have Ca2+ levels that averaged 189 +/- 2 nM. The distribution of Ca2+ within these fibres appeared uniform. 6. The population of dystrophic fibres that possessed morphological abnormalities maintained even higher Ca2+ concentrations (368 +/- 3 nM). Several fibres from this morphological group displayed obvious heterogeneity in Ca2+ distribution with distinct, localized areas of higher Ca2+. 7. These results support the contention that Ca2+ homeostasis is markedly impaired in dystrophic muscle. The elevated Ca2+ levels are near the threshold for contraction and, together with severe morphological fibre abnormalities, are probably centrally involved in fibre necrosis apparent in muscular dystrophy. PMID- 2231411 TI - Effect of melittin on renin and prostaglandin E2 release from rat renal cortical slices. AB - 1. The present experiments were designed to determine the effect of melittin on renin secretion. Melittin is a polypeptide component of bee venom which stimulates phospholipase A2 activity, thereby increasing arachidonic acid release and prostaglandin (PG) synthesis, and which inhibits protein kinase C activity. Either of these actions might be expected to stimulate renin secretion, since renin secretion is stimulated by arachidonic acid and by several PGs, and since renin secretion is inhibited by several activators of protein kinase C. 2. In rat renin cortical slices incubated at 37 degrees C in a buffered and oxygenated physiological saline solution, 0.1-10 microM-melittin produced a concentration dependent stimulation of both prostaglandin E2 (PGE2) synthesis and renin secretion. However, melittin-stimulated renin secretion is independent of melittin-stimulated phospholipase A2 activity, arachidonic acid release, and PG synthesis, since 20 microM-quinacrine (a phospholipase A2 antagonist) and 50 microM-meclofenamate (a cyclooxygenase antagonist) antagonized basal and melittin stimulated PGE2 synthesis but had no effects on basal or melittin-stimulated renin secretion. 3. Furthermore, melittin-stimulated renin secretion is not produced by inhibition of protein kinase C, since an activator of protein kinase C (12-O-tetradecanoylphorbol 13-acetate, TPA), enhanced rather than antagonized melittin-stimulated renin secretion. Ouabain partially antagonized, but did not completely block, melittin-stimulated renin secretion. 4. Thus, melittin stimulated phospholipase A2 activity probably accounts for stimulated PGE2 production, but not for stimulated renin secretion. The mechanism of melittin stimulated renin secretion is unclear; an effect on protein kinase C does not appear to be involved, and in contrast to the stimulatory effects of a variety of other substances, melittin-stimulated renin secretion is only partially antagonized by ouabain. PMID- 2231413 TI - An ATP-activated conductance in pheochromocytoma cells and its suppression by extracellular calcium. AB - 1. ATP-activated inward current in PC12 pheochromocytoma cells was characterized using the whole-cell voltage-clamp technique. 2. ATP (100 microM) applied extracellular elicited an inward rectifying current with a reversal potential of about +7 mV. The current was desensitized in seconds in spite of continued presence of ATP. 3. A comparison was made of the ability of ATP and its analogues. The order of potency in activating the inward current was ATP greater than ATP gamma S greater than ADP; AMP, adenosine and alpha, beta-methylene ATP were inactive at concentrations up to mM. 4. The ATP-activated current was also observed when external Na+ and Ca2+ were replaced with K+, TEA, Tris or glucosamine. The order of ion selectivity was Na+ greater than K+ greater than TEA not equal to Tris greater than glucosamine. 5. The ATP-activated current was also recorded in extracellular solutions containing Ca2+ as the only external cation. The amplitude increased as the concentration of Ca2+ was increased in the range between 1.8 and 16.2 mM. However, the current amplitude decreased at higher Ca2+ concentrations and the current was not recorded in 110 mM-Ca2+ solution. 6. In the presence of 140 mM-Na+ in the external solution, the current amplitude also decreased as the external Ca2+ concentration was increased (from 1.8 to 16.2 mM). 7. The results indicate that Ca2+ as well as monovalent cations permeate through the ATP-sensitive pathway and that Ca2+ blocks ion permeation, including its own permeation through the pathway. This regulation by extracellular Ca2+ is different to the ATP-activated current in smooth muscle cells. PMID- 2231414 TI - Voltage-dependent currents in isolated cells of the frog retinal pigment epithelium. AB - 1. Retinal pigment epithelial (RPE) cells were isolated enzymatically from bullfrog retinae. The patch-clamp technique was employed to investigate whole cell currents under voltage-clamp conditions. 2. Isolated RPE cells were columnar or cuboidal in form, often with long processes protruding from the apical surface. Distinct apical and basal membrane domains were maintained for several hours following isolation. 3. The mean membrane capacitance was 62 pF. The resting potential averaged -30 mV, but it was as high as -75 mV in some cells. 4. Three voltage-dependent currents were observed: a time-independent and inwardly rectifying current and two time-dependent outwardly rectifying currents that had distinct kinetic properties. 5. Voltage pulses from a holding potential of -70 mV to potentials ranging from -30 to -120 mV produced membrane currents that were essentially time independent. The I-V relationship in this voltage range depended on the resting potential. It was usually inwardly rectifying in cells with resting potentials negative to about -50 mV, but tended to be linear in cells with more positive potentials. Three observations strongly suggested that the inwardly rectifying current is carried by K+. First, increasing the extracellular K+ concentration [( K+]) from 2 to 112 mM shifted the zero-current potential of the I-V relationship in the positive direction from an average value of -60 mV to 0 mV. Second, the addition of the K+ channel blockers Ba2+ (2 mM) or Cs+ (5 mM) to the extracellular solution inhibited a major component of the inwardly rectifying current. Finally, the reversal potential (Vr) of the Ba2(+)-sensitive current averaged -90 mV, near the K+ equilibrium potential (EK). 6. In approximately 50% of the cells, depolarizing voltage pulses to potentials more negative than -30 mV evoked an outward current that resembled the delayed rectifier present in other non-excitable cells. It activated with sigmoidal kinetics in less than 100 ms following a brief delay and then declined exponentially with a time constant of approximately 1 s. The peak chord conductance associated with this current was half-maximal at +14 mV. Several observations indicated that this outwardly rectifying current is carried primarily by K+: its Vr closely matched EK over a wide range of extracellular [K+]; it was inhibited 80% by exposure to the K+ channel blockers 4-aminopyridine (1 mM) and tetraethylammonium (20 mM); and it was abolished by intracellular dialysis with a K(+)-free solution.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231415 TI - Central action sites of interleukin-1 beta for inducing fever in rabbits. AB - 1. Intravenous (I.V.) human recombinant interleukin-1 beta (IL-1 beta) in high doses caused biphasic fever in rabbits. In lower doses it produced only the first phase of fever. 2. Intracerebroventricular (I.C.V.) or intrapreoptic-anterior hypothalamic (IPOAH) injection of IL-1 beta produced a rather rapid and marked increase in rectal temperature. 3. Subcutaneously administered indomethacin partly reduced the first phase and more substantially the second phase of the biphasic fever induced by high doses of I.V. IL-1 beta. The first phase may thus be prostaglandin independent at least in part. 4. In the fever induced by I.C.V. injection of IL-1 beta, subcutaneous indomethacin reduced the elevation of the rectal temperature considerably and delayed the onset of fever. Administration of indomethacin (I.C.V.) caused marked inhibition of the fever induced by a lower I.C.V. dose of IL-1 beta, but with a high dose the onset of the fever was delayed for about 1 h, without the total rise being affected. 5. It is concluded that the first phase of biphasic fever is caused by IL-1 beta acting via an extravascular component of the organum vasculosum laminae terminalis (OVLT) or the circumventricular organs accessible from only the blood side, to release arachidonate metabolites, presumably prostaglandin E2 (PGE2), and the second phase by IL-1 beta acting via the blood-brain interface accessible both from the blood side and the brain side, to release metabolites other than PGE2. PMID- 2231416 TI - Sympathetic-parasympathetic interactions at the heart, possibly involving neuropeptide Y, in anaesthetized dogs. AB - 1. Stimulation of cardiac sympathetic nerves caused prolonged inhibition of vagal effects on heart rate, an effect which has been proposed on the basis of previous studies to be due to neuropeptide Y or a neuropeptide Y-like substance, released from the sympathetic nerves. 2. This prolonged vagal inhibitory effect was attenuated or abolished when the sympathetic stimulation responsible was given together with continuous vagal stimulation. 3. Continuous vagal stimulation alone did not modify the ability of administered neuropeptide Y to cause inhibition of cardiac vagal action. 4. The results are consistent with the cardiac vagal nerves releasing a transmitter (probably acetylcholine) which acts on cardiac sympathetic nerve endings, inhibiting them from releasing neuropeptide Y or a neuropeptide Y-like substance. PMID- 2231417 TI - Selective control of sympathetic pathways to the kidney, spleen and intestine by the ventrolateral medulla in rats. AB - 1. Electrical activity of multifibre renal, splenic, mesenteric and greater splanchnic nerves and 13th thoracic white rami was recorded in artificially respired, urethane-anaesthetized rats. Discharge of neurones in the rostral ventrolateral medulla was blocked by unilateral microinjections of the inhibitory amino acid glycine and effects on the electrical activity of these sympathetic nerves were compared. 2. Blockade of the rostral ventrolateral medulla caused greater decreases in discharge of renal than splenic nerves and had no consistent effect on mesenteric nerves. This blockade also decreased the discharge of the preganglionic white rami more than that of the preganglionic splanchnic nerves. 3. Postganglionic responses to rostral ventrolateral medulla blockade were always greater than preganglionic responses. 4. The arterial pressure and renal nerve responses to rostral ventrolateral medulla blockade in urethane-anaesthetized rats were not different from those in rats anaesthetized with alpha-chloralose. 5. These findings demonstrate that pre- and postganglionic sympathetic pathways to the kidney are more dependent upon excitatory drive from the rostral ventrolateral medulla than pathways directed to the spleen and intestine. PMID- 2231418 TI - Activation of human respiratory muscles during different voluntary manoeuvres. AB - 1. This study used three techniques (bilateral phrenic nerve stimulation, motor cortex stimulation and quantitative electromyography) to assess the degree of activation of the diaphragm, intercostal-accessory muscles and abdominal muscles during postural tasks and respiratory manoeuvres. They included maximal inspiratory and expulsive efforts. 2. Bilateral phrenic nerve stimuli at supramaximal levels produced an average change in transdiaphragmatic pressure (Pdi) of 28 cmH2O during relaxation. During maximal inspiratory or expulsive efforts, all subjects were able to activate the diaphragm fully at functional residual capacity as judged by the failure of stimuli delivered during the voluntary efforts to increase Pdi. Peak voluntary Pdi was about 30% less for inspiratory than expulsive manoeuvres. 3. By contrast, transcranial activation of motor cortical output to the diaphragm and abdominal muscles produced an increment in abdominal pressure of 25 +/- 7 cmH2O during maximal voluntary expulsive efforts. Given the lack of response to phrenic nerve stimulation at similar voluntary pressures, this suggests that abdominal muscles, and not the diaphragm, fail to generate their full contractile force during maximal voluntary expulsive manoeuvres. 4. Motor cortical stimulation during weak inspiratory efforts produced a small reduction in oesophageal pressure (i.e. increase in net inspiratory force) of 7-14 cmH2O. This response could not be extinguished during maximal voluntary inspiratory efforts in two of three subjects. This occurred despite the cortical co-activation of 'antagonist' muscles in the chest wall and abdomen, and passive transmission of pressure from the abdominal to thoracic compartments. 5. Integrated electromyographic activity (EMG) recorded from abdominal muscles (rectus abdominis, external oblique) was greater during trunk flexion than during maximal expulsive efforts. Similarly, integrated EMG of the intercostal-accessory muscles (sternomastoid, scalenes, parasternal intercostals) was greater during tasks requiring head and/or neck flexion than during the maximal inspiratory efforts. 6. These data show that the diaphragm can be fully activated by the central nervous system during voluntary respiratory tasks but that other agonist 'respiratory' muscles need not be activated fully. Given the complex actions of 'inseries' respiratory muscles revealed here, it is argued that differences in the transdiaphragmatic pressure during various postural and respiratory tasks do not necessarily imply variation in the level of diaphragmatic neural drive. PMID- 2231419 TI - Responses of type I cells dissociated from the rabbit carotid body to hypoxia. AB - 1. The carotid body chemoreceptors are stimulated in situ by hypoxia. We have studied type I cells freshly dissociated from the carotid body of the rabbit. We have used microfluorimetric and patch clamp techniques to examine the responses to hypoxia, to anoxia, and to metabolic inhibition. 2. NADH autofluorescence measured at both 400 and 500 nm increased rapidly and reversibly in response to anoxia or to cyanide (CN-), reflecting a change in mitochondrial metabolism. 3. Indo-1 was used to measure changes in intracellular calcium, [Ca2+]i. Anoxia reversibly increased [Ca2+]i from approximately 50-100 to approximately 200-450 nM in all cells tested. The response showed a striking temperature sensitivity. Responses to hypoxic stimuli were barely detectable at 17-20 degrees C, and were dramatically increased on warming to 36 degrees C. In contrast, responses to K(+) induced depolarization were only slightly increased in rate of onset and recovery by warming. 4. The rise in [Ca2+]i originated largely from an intracellular store which was slowly depleted by exposure to nominally Ca2(+)-free solutions. Responses were unaffected by blockade of Ca2+ channels with organic (D600, verapamil) or inorganic (Co2+) blockers, by blockade of Na+ channels with tetrodotoxin (TTX), or by increasing action potential duration with tetraethylammonium (TEA). Responses to anoxia were increased by the increased [Ca2+]i loading that follows prior exposure to Ca2(+)-free solutions. 5. Responses to anoxia, to blockade of electron transport by CN-, and to the mitochondrial uncoupler, carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP), were equivalent in amplitude. The response to anoxia was occluded by concurrent application of FCCP, suggesting that the Ca2+ originates from the same pool in each case. 6. At 35-36 degrees C, responses to graded levels of PO2 were also graded. Thresholds varied between cells, but were typically 30-50 mmHg. Stimulus-responses curves were essentially hyperbolic, increasing dramatically as the PO2 approached 0 mmHg. 7. The sensitivity of cells to hypoxic solutions was increased by acidification of the superfusate over the pH range from 7.3 to 6.85. 8. Cell-attached patch clamp recordings showed depression of spontaneous action potentials associated with a rise in [Ca2+]i during exposure to anoxic solutions. Whole-cell recordings showed that anoxia increased a voltage-gated gK as described previously for CN-, while producing no change in resting conductance. 9. These data suggest that the rise in [Ca2+]i originates largely from Ca2+ efflux from a mitochondrial pool.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231421 TI - Maturation of the cutaneomuscular reflex recorded from the first dorsal interosseous muscle in man. AB - 1. Cutaneous reflexes have been recorded from the first dorsal interosseous muscle following electrical stimulation of the digital nerves of the index finger in man. Recordings have been obtained from 127 children, aged from 3 to 18 years while each performed an isometric abduction of the index finger and whole hand grips. 2. In the adult, reflexes recorded while subjects performed an isometric abduction of the index finger consisted of three readily identifiable components within the first 100 ms. These were an initial short spinal latency increase in EMG (E1), followed by a decrease (I1), followed by a prominent longer-latency increase (E2) which was normally larger in size than the shorter-latency increase. 3. The configuration of the reflex changed during development. When recorded during an abduction, the E1 component was present in all children and showed a small but progressive reduction in size with age. With increasing age, both the I1 and E2 components were present in an increasing proportion of children and increased in size until the adult configuration was reached at 14-15 years. 4. Comparison of reflexes recorded during sustained whole hand grips with reflexes recorded during an isometric index finger abduction revealed differences in all three components. When recorded during those grips used in the present study the E1 component was generally significantly larger while the I1 component was generally significantly smaller than when recorded during index finger abduction. At all ages the E2 component was significantly smaller when recorded during a grip. 5. The configuration of the reflex during an isometric index finger abduction was compared with the ability of the child to perform rapid finger movements. Those children who had no E2 component tended not to perform well in the tests of rapid finger movement. However, there was no simple relationship between the size of the E2 component and ability to produce rapid finger movements. PMID- 2231420 TI - Rabbit sino-atrial node cells: isolation and electrophysiological properties. AB - 1. A method has been developed for isolating calcium-tolerant, single rabbit sinoatrial node cells which maintain their natural shape following isolation. The majority of viable, spontaneously active cells were elongated and measured about 100 microns in length. 2. Staining fixed cells with Haematoxylin-Eosin revealed that a 'cell' with projections was usually an aggregate of more than one cell. 3. Single, elongated, spontaneously active cells were current and voltage clamped using the whole-cell configuration of the patch-clamp recording technique. The spontaneous activity and time-dependent currents recorded were similar to those reported previously in multicellular nodal preparations and in single cells. 4. An assessment was made of the time course of L-type calcium current run-down: a stable period of between 10 and 20 min followed by a rapid run-down (over about 2 min) was typically observed. 5. In most cells, a fast, TTX-sensitive Na+ current component was seen. A few cells showed a transient outward K+ current (iA). 6. The activation range for the hyperpolarization-activated current, if, varied from cell to cell. In the majority of actively beating cells, the threshold for if was near the maximum diastolic potential (about -65 mV in most cells) but in other cells, no if could be recorded within the pacemaker range. 7. Millimolar concentrations of MnCl2 caused a marked increase in if, but only when the pipette solution did not contain EGTA. Inclusion of EGTA (to buffer Ca2+ to about pCa 8) significantly reduced the effect of Mn2+ which therefore probably occurs through inhibition of Na(+)-Ca2+ exchange and consequent rise in intracellular Ca2+ concentration. PMID- 2231422 TI - Mirror movements studied in a patient with Klippel-Feil syndrome. AB - 1. Electromyographic (EMG) recordings have been made from upper limb muscles in a patient with well-defined congenital mirror movements occurring in association with Klippel-Feil syndrome and the results compared to those obtained in normal control subjects. 2. In the patient, liminal percutaneous electrical or magnetic brain stimulation applied over either hemisphere elicited bilateral and symmetrical short-latency muscle responses in relaxed intrinsic hand muscles. In the normal subjects unilateral brain stimulation only elicited contralateral muscle responses. 3. F response and H reflex studies for the patient's ulnar supplied intrinsic hand muscles were normal. No crossed responses were recorded in the homologous muscles of the contralateral hand. 4. Scalp-recorded somatosensory-evoked responses following ulnar or median nerve stimulation were of normal latency and distribution in the patient. 5. In the patient, cross correlation analysis of on-going single and multiunit needle EMGs recorded between muscles of left and right hands revealed a central peak in the cross correlogram. No cross-correlogram peaks were found between left- and right-hand muscles in normal subjects. The magnitude and time course of the central peaks in the cross-correlograms constructed between the firing of motor units on opposite sides of the body in the patient were similar to those found in cross correlograms constructed between the firing of motor units from muscles on the same side of the body in the patient and in normal subjects. 6. The magnitude of cross-correlogram peaks detected within a muscle and those detected between left and right homologous muscles showed a gradient in which the largest peaks were found in the intrinsic hand and forearm extensor muscles. The smallest peaks were observed in the forearm flexor muscles. No peaks were detected between left and right biceps brachii muscles. In intrinsic hand muscles, the size of the cross correlogram peak detected between the EMGs of homologous muscle pairs was greater than that found for non-homologous muscle pairs. 7. Cutaneous reflex responses were recorded from first dorsal interosseous muscle following unilateral electrical stimulation of the digital nerves of the index finger. In the patient, this produced an early excitatory (E1) response on the stimulated side. Later excitatory (E2 and E3) responses, of approximately equal size and latency, were distributed bilaterally. In the normal subjects, reflex responses were confined to the stimulated side.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231423 TI - Measurement of intracellular calcium and pH in avian neural crest cells. AB - 1. Intracellular pH (pHi) and calcium (Cai2+) were studied in freely migrating neural crest cells and in closely packed non-migrating cells derived from avian neural tubes in vitro, using the fluorescent dyes 2,3-dicyanohydroquinone (DCH) and Indo-1 to measure pHi and Cai2+ respectively. 2. In freely migrating crest cells the pHi was approximately 0.2 pH units more alkaline and Cai2+ 90 nM lower than in closely packed cells. 3. Experiments to establish the cellular mechanisms regulating pHi in isolated neural crest cells demonstrate the presence of Na(+) H+ exchange in 66% of the cells and Na(+)-HCO3(-)-dependent pHi-regulating mechanisms in all cells examined. 4. Interactions between pHi and Cai2+ were examined. pHi was altered using either NH4Cl pulses resulting in small changes in Cai2+ or using a weak acid and base (propionate and trimethylamine), which produced a fall and a rise in Cai2+ respectively. 5. Exposure to Ca2(+)-free media caused a lowering of Cai2+ and induced a transient acidification. 6. Application of BAPTA-AM (50 microM), a cell-permeant analogue of EGTA, resulted in a fall in Cai2+ and an intracellular acidification. 7. Co2+ and La3+ (2 mM) each induced a reversible fall in Cai2+ that was accompanied by intracellular acidification. These data suggest the presence of a transmembrane flux of Ca2+ in the resting cells. 8. It would appear that the mechanisms influencing Cai2+ and pHi are linked. This idea is discussed in terms of possible mechanisms and roles for Ca2+ and pH as modulators of neural crest cell behaviour. PMID- 2231424 TI - On the localization of the stretch reflex of intrinsic hand muscles in a patient with mirror movements. AB - 1. The patient studied showed the typical mirror movements of the Klippel-Feil syndrome. Earlier intensive electrophysiological analysis suggests that many of her corticospinal axons branch abnormally to supply motoneurones on both sides of the spinal cord. Thus, in her, a long-latency reflex utilizing the motor cortex should manifest itself bilaterally. 2. EMG recordings were made simultaneously from the first dorsal interosseous (FDI) muscles of both hands while they were being voluntarily activated by the subject. The FDI of one hand was then briefly stretched by forcibly adducting the index finger. Similar but more limited studies were made using flexor pollicis brevis. 3. The reflex response of the stretched muscle consisted of a typical mixture of early (M1) and late (M2) components, with mean latencies of 32 and 49 ms respectively. 4. Unlike normal controls, the contralateral muscle responded on stretch of the ipsilateral muscle. However, its response consisted solely of a long-latency reflex. This was comparable in size, latency and waveform to the ipsilateral late component. (Mean size, 84% of the ipsilateral M2 response; mean latency 46 ms, or 3 ms less than the ipsilateral response due to the absence of M1). 5. The short-latency response did not spread to the homologous contralateral muscle even when it was large ipsilaterally. The long-latency response elicited from FDI did not spread to the abductor digiti minimi muscle of either hand. 6. Reducing the duration of the stretch reduced the duration of the crossed response by an equivalent amount. Unloading the ipsilateral muscle produced a delayed reduction of EMG activity contralaterally. Thus her long-latency pathway can act tonically as well as phasically. 7. These findings strongly support the hypothesis that delayed components of the human stretch reflex are relayed via the motor cortex and the corticospinal tract. PMID- 2231425 TI - Neuronal activity in the lateral cerebellum of trained monkeys, related to visual stimuli or to eye movements. AB - 1. The responses of neurones in the lateral cerebellar cortex to visual stimuli and to eye movements were recorded in rhesus monkeys trained to perform visually guided arm and eye movements in a tracking task. 2. Twenty-two of 134 units recorded (16%) modulated their discharge in response to a bright Xenon flash. They were mainly located in the dorsal paraflocculus. Among those identified as Purkinje cells both simple spike and climbing fibre responses to the flash were seen. (72% of the units were related to arm movements; these were centred in the paramedian lobule, and have been described fully in Marple-Horvat & Stein (1987).) 3. The visual responsiveness of one of the units varied according to the phase of the monkey's task. Around the time that the target stepped, which was the monkey's cue to move, its sensitivity to other stimuli disappeared. 4. Only two neurones responded to the movements of the tracking target. These responses were conditional upon the monkey using visual signals to guide his movements; they did not respond to the target step if he moved before the target did. 5. Fourteen units (10%) located in crus I and II and lobulus simplex correlated strongly with the velocity of horizontal eye movements. Only one of these also responded to visual stimuli. 6. Thus most neurones were found to carry only visual, or eye movement, or limb movement information rather than combinations of these signals; they were located in different but overlapping regions of lateral cerebellar cortex. Visually responsive neurones are probably involved in planning the visual goal of movements, while eye and arm movement neurones probably help to create co-ordinative structures for executing voluntary eye and arm movements. PMID- 2231426 TI - Synaptic excitation of inhibitory cells by single CA3 hippocampal pyramidal cells of the guinea-pig in vitro. AB - 1. In simultaneous recordings from pairs of neurones in hippocampal slices from guinea-pigs, single action potentials fired by CA3 pyramidal cells could initiate inhibitory postsynaptic potentials (IPSPs) in nearby pyramidal cells. 2. The latencies of these IPSPs could be as short as 3 ms. However, they were mediated disynaptically via chemical, excitatory synapses, since inhibitory coupling was suppressed by an excitatory amino acid antagonist. 3. The properties of excitatory synapses made onto inhibitory cells were examined to assess the basis for this strong coupling. Inhibitory cells were identified either by showing that they inhibited another cell or by their characteristic firing pattern. 4. Excitatory postsynaptic potentials (EPSPs) elicited by single pyramidal cell action potentials had a mean amplitude of 1-4 mV and a time to peak of 1.5-4 ms. In most cases they decayed with a time constant similar to that of the inhibitory cell membrane. 5. EPSP amplitude increased with hyperpolarization of the postsynaptic membrane. Membrane polarization had little effect on EPSP shape. 6. EPSPs fluctuated in amplitude and transmission sometimes failed, suggesting transmission was quantal and that few quanta were released. 7. When presynaptic cells were made to fire bursts of action potentials, EPSPs in inhibitory cells were initially potentiated. 8. EPSPs could cause inhibitory cells to fire. The interval between pre- and postsynaptic spikes could be as short as 2.5 ms and the probability of spike transmission could be as high as 0.6. Some inhibitory cells which received feedback excitation were also excited in feedforward fashion by mossy fibre stimuli. 9. One pyramidal cell could activate several disynaptic inhibitory pathways terminating on another pyramidal cell. This suggests that excitatory synapses made by pyramidal cell axon collaterals onto inhibitory cells are divergent. 10. This strong, divergent excitation of inhibitory cells ensures recurrent inhibition is sufficiently widespread, rapid and potent to control the spread of activity by recurrent excitatory connections between CA3 pyramidal cells. PMID- 2231427 TI - Muscle injury, cross-sectional area and fibre type distribution in mouse soleus after intermittent wheel-running. AB - 1. It was previously noticed that mouse soleus, but not extensor digitorum longus (EDL) muscles, suffer fibre damage at the onset of voluntary wheel-running without further injuries thereafter. 2. In CBA/J mice trained continuously for 5 months and rested for periods of 1, 2, 3, 4 and 5 weeks acute muscle damage was found in soleus 7 days after the resumption of wheel-running. On single cross sections damage was present on average in 8.7 +/- 3.5% (mean +/- S.D., n = 15) of the fibres, but only in 0.47 +/- 0.21% (n = 9) and 1.3 +/- 1.1% (n = 4) in control animals rested for 0-6 weeks after continuous running or in untrained controls. 3. Repeated muscle damage occurred when mice exercised for 4 days at intervals of 21-25 days, and after thirteen running episodes within 12 months marked changes in soleus, but not EDL muscles, were present. In cross-sections the total number of muscle fibre profiles was significantly larger in soleus of intermittent runners (768 +/- 68, n = 6; P less than 0.05), compared to continuous runners (676 +/- 54, n = 3) and sedentary animals (683 +/- 33, n = 4). This is probably due to incomplete repair which results in 'split fibres'. 4. At the same time total muscle fibre cross-sectional area was significantly elevated in intermittent runners (P less than 0.05), mainly due to increase in fibre diameters. Net cross-sectional areas were 0.59 +/- 0.069 mm2 (n = 6) in intermittent, 0.53 +/- 0.076 mm2 (n = 3) in continuous runners and 0.46 +/- 0.031 mm2 (n = 3) in sedentary controls. 5. Tetanic and twitch force were also significantly elevated in soleus of intermittent runners while the ratio force/area remained the same. 6. There was an increase in the proportion of type I fibres in soleus from 75 +/- 0.9% (n = 4) in untrained controls to 90 +/- 4.4% (n = 6; P less than 0.05) in intermittent runners and 81 +/- 5.6% (n = 3; n.s.) in continuous runners. 7. Resistance to block of synaptic transmission in soleus was significantly higher in intermittent runners for two levels of curare, indicating enhanced safety margins. 8. EDL muscles in intermittent runners were not different from sedentary controls in any of the parameters studied. In particular, muscle fibres with signs of previous damage (split fibres, central nuclei) were rare (on average 0.5-0.6%) and equally frequent in all experimental groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231428 TI - The frequency of isomerization-like 'dark' events in rhodopsin and porphyropsin rods of the bull-frog retina. AB - 1. The dark current and responses to dim flashes were recorded with the suction pipette technique from single rods in pieces of bull-frog retina taken from either the dorsal porphyropsin or the ventral rhodopsin field. 2. The composition of visual pigment in the rods was determined by microspectrophotometry. Rods from the dorsal pieces contained 70-88% porphyropsin523 mixed with rhodopsin502. The ventral rods contained almost pure rhodopsin, any possible admixture of porphyropsin being below the level of detectability (less than 5%). 3. In most cells, the responses to dim flashes were well fitted by a four-stage linear filter model, with no systematic differences in the response kinetics of porphyropsin and rhodopsin rods. The amplitude of saturated responses varied between 8 and 55 pA and that of responses to single isomerizations between 0.4 and 3.5 pA. 4. In porphyropsin rods, discrete events similar to the response to one photoisomerization were clearly seen in complete darkness. The dark current amplitude histogram was fitted by a convolution of the probability densities for the Gaussian continuous noise component and the averaged dim-flash response waveform. This allows estimation of the frequency and amplitude of discrete events and the standard deviation of the continuous component. The mean frequency of discrete dark events thus obtained from six porphyropsin cells was 0.057 rod-1 s-1 at 18 degrees C. 5. In rhodopsin rods, the dark current amplitude histogram appeared completely symmetrical, indicating that the frequency of discrete events must be lower than 0.005 rod-1 s-1 (except in one rod where it was 0.006 events rod-1 s-1). Per molecule of rhodopsin, the events are then at least 5 times rarer than reported for toad rhodopsin rods at the same temperature. 6. The low rate of isomerization-like 'dark' events in bull-frog rhodopsin rods shows, firstly, that results cannot be generalized across species even for rhodopsins which appear spectrally identical. Secondly, it suggests that these events need not (in an evolutionary sense) constitute an irreducible noise factor which must set the ultimate limit to the sensitivity of dark-adapted vision. 7. The difference between porphyropsin and rhodopsin rods shows that, given (presumably) the same opsin, the pigment utilizing retinal2 and absorbing maximally at longer wavelengths produces more noise. The signal/noise ratio attained in the photoreceptor may be an important factor in the natural selection of visual pigments. PMID- 2231429 TI - Nucleus tractus solitarius as mediator of evoked parabrachial cardiovascular responses in the decerebrate rabbit. AB - 1. The present study has assessed the importance of neurones within the nucleus tractus solitarius (NTS) in mediating the cardiovascular response evoked from the parabrachial nucleus (PBN) in the decerebrate rabbit. Microinjection techniques were employed so that the magnitude of the circulatory responses elicited from the PBN could be compared before, and after, kainic acid or bicuculline were microinjected into restricted regions of the NTS. 2. Electrical stimulation of the PBN (both medial and lateral regions) evoked variable changes in heart rate, a pressor response, vasoconstriction in the hindlimb and an increase in renal sympathetic nerve activity. Glutamate injected into these regions of the PBN elicited a similar pattern of response except that a tachycardia was observed consistently. 3. Both electrical and chemical stimulation of restricted regions of the NTS evoked bradycardia and a depressor response together with an increase in femoral vascular conductance and an inhibition of activity in the renal nerve. 4. Chemical lesions placed in these regions of the NTS by microinjecting kainic acid were found to attenuate both the heart rate and arterial blood pressure responses elicited from sites in the medial and lateral PBN using either electrical or chemical stimulation. Equivalent effects were produced on microinjecting the GABAa receptor antagonist bicuculline into the NTS. 5. These data indicate that NTS neurones play a part in mediating the cardiovascular responses that are evoked from the PBN and suggest that the action of the PBN at the level of the NTS is mediated via a GABAergic mechanism. PMID- 2231430 TI - Characteristics of miniature inhibitory postsynaptic currents in CA1 pyramidal neurones of rat hippocampus. AB - 1. Recordings were made in vitro from chloride-loaded CA1 rat hippocampal pyramidal neurones in the presence of tetrodotoxin (TTX) to examine miniature inhibitory postsynaptic currents (IPSCs). 2. Most spontaneous synaptic events recorded before TTX was applied, and all events that were resolved in the presence of TTX, were blocked by the GABAA receptor antagonist bicuculline. 3. At 25 degrees C, averaged miniature IPSCs had time to peak of about 3 ms and in most cases decayed with a single time constant close to 25 ms. 4. With a driving force for chloride ions between 70 and 80 mV, the mean miniature IPSC amplitude was 19.6-27.9 pA, yielding a conductance of 258-326 pS. The mean amplitude of unitary IPSCs recorded before TTX was applied was in the range of 31-73 pA. 5. When intervals between miniature IPSCs were compared with an exponential distribution, there was an excess of events at intervals shorter than 5 ms. Some individual events appeared to represent the nearly simultaneous release of two inhibitory quanta. 6. Miniature IPSC amplitude distributions were better fitted with the sum of two Gaussians than with one Gaussian. The variance in amplitude of a single quantal event exceeded that of the baseline noise. 7. Comparison of the conductance changes corresponding to the first Gaussian distribution with single GABA channel data suggests that one inhibitory quantum opens twelve to twenty chloride channels and that GABA molecules bind once to a postsynaptic receptor. PMID- 2231431 TI - Effects of tension and stiffness due to reduced pH in mammalian fast- and slow twitch skinned skeletal muscle fibres. AB - 1. The pH dependence of the Ca2+ sensitivities of isometric tension and stiffness was investigated at 10 and 15 degrees C in skinned single fibres from rat and rabbit fast- and slow-twitch skeletal muscles. Stiffness was determined by recording the tension responses to sinusoidal length changes (3.3 kHz); peak-to peak amplitude of the length change was monitored by laser diffraction and averaged approximately 1.3 nm (half-sarcomere)-1. We have assumed that stiffness provides a measure of the number of cross-bridge attachments to actin. 2. At maximal Ca2+ activation, stiffness was depressed by 22 +/- 2% (mean +/- S.E.M.) in fast-twitch fibres but was unchanged in slow-twitch fibres when pH was lowered from 7.00 to 6.20. As reported previously, maximum tension was depressed by 20 45% at low pH, with the effect being greater in fast-twitch compared to slow twitch fibres. 3. In fast-twitch fibres at 10 and 15 degrees C the Ca2+ concentrations for half-maximal activation of tension and stiffness were increased at low pH. In slow-twitch fibres, similar effects were observed at 15 degrees C, but at 10 degrees C there were no changes in the Ca2+ sensitivities of tension and stiffness when pH was lowered. 4. Linear relationships between relative tension and relative stiffness were obtained at all temperatures, with slopes of 1.04 +/- 0.01 at pH 7.00 and 0.76 +/- 0.01 at pH 6.20 in fast- and slow twitch fibres, indicating that force per cross-bridge attachment is similarly reduced at low pH in both types of fibres. 5. In both fast- and slow-twitch fibres, rigor tension (no added ATP or creatine phosphate; pCa 9.0) was depressed by 35 +/- 7% and stiffness by 12 +/- 4% when pH was reduced from 7.00 to 6.20. Since cross-bridge cycling is inhibited in rigor the effect of low pH to depress rigor tension suggests that pH directly modulates the strength of the bond formed between actin and myosin. 6. The effect of low pH to reduce the apparent number of cross-bridge attachments during maximal Ca2+ activation in fast- but not slow twitch fibres could account for the greater H(+)-induced depression of maximum force in fast-twitch fibres. In both fibre types, the decrease in the number of cross-bridge attachments at submaximal concentrations of Ca2+ may in part account for the loss in Ca2+ sensitivity of tension at low pH, due perhaps to a reduction in co-operative activation of the thin filament by bound cross-bridges. PMID- 2231434 TI - Assessment of the value of immunofluorescence microscopy in the diagnosis of oral mucosal lichen planus. AB - Accurate diagnosis of oral mucosal lichen planus (OMLP) is essential if appropriate management is to be instituted. Direct immunofluorescence microscopy (DIF) has facilitated the diagnosis of some dermatologic diseases with oral manifestations, but its use in the diagnosis of OMLP is less well documented. In the present study, 165 biopsies from consecutive cases for which a provisional diagnosis of OMLP was suggested clinically or on the basis of routine histopathologic, or DIF assessment were studied. In 27 cases the results of DIF were non-contributory. In 13 cases the diagnosis could only be established by DIF examination. Nine cases clinically diagnosed as OMLP were assigned to a different condition on the basis of routine histology and DIF. It was concluded that DIF was an integral step in the diagnosis of OMLP. PMID- 2231432 TI - pH modulation of the kinetics of a Ca2(+)-sensitive cross-bridge state transition in mammalian single skeletal muscle fibres. AB - 1. The rate constant of tension redevelopment (ktr) following a rapid release and subsequent re-extension of muscle length has been demonstrated to be Ca2+ sensitive and is thought to reflect the rate-limiting step in the cross-bridge cycle leading to the formation of the strongly bound, force-bearing state. The kinetics of this cross-bridge state transition were investigated at 15 degrees C over a wide range of Ca2+ concentrations while varying pH from 7.00 to 6.20 in rat slow-twitch soleus, rat fast-twitch superficial vastus lateralis (SVL) and rabbit fast-twitch psoas skinned single fibres. 2. At maximal levels of Ca2+ activation, ktr was unaffected by changes in pH from 7.00 to 6.20 while isometric tension was depressed to 0.60 +/- 0.02 P0 (mean +/- S.E.M.) at the low pH in fast twitch fibres and to 0.78 +/- 0.01 P0 in slow-twitch fibres (P0 is the maximum isometric tension obtained at pH 7.00). 3. At reduced levels of Ca2+ activation, corresponding to pCa (-log [Ca2+]) greater than 5.0, ktr was markedly depressed in all fibre types when pH was lowered. The Ca2+ sensitivity of steady-state isometric tension was also reduced in all fibres at pH 6.20 compared to pH 7.00. 4. The results suggest that pH has a modulatory effect upon an apparent rate constant which is rate limiting in terms of the formation of the strongly bound, force-bearing cross-bridge state. This effect of altered pH may in part account for the reduction in the Ca2+ sensitivity of isometric force at low pH as well as the depression of the rate of rise of tension in living fibres during fatiguing stimulation. PMID- 2231433 TI - Oxytocin excites gastric-related neurones in rat dorsal vagal complex. AB - 1. Dorsal medullary injections of oxytocin (OT) influence gastric motor and secretory function via a vagally mediated mechanism. Thus, it was hypothesized that OT altered the firing rate of brain stem vagal neurones that were specifically related to gastric function. 2. To study this, glass microelectrode/injection pipette arrays were used to record the activity of gastric-related neurones in the dorsal vagal complex (DVC), which includes vagal sensory neurones in the nucleus tractus solitarius (NTS) and motor neurones in the dorsal motor nucleus (DMN). After identifying such a neurone, spontaneous activity was monitored before and after micropressure injection of OT and vehicle solutions from the pipettes. 3. Two methods were used to identify neurones that were related to gastric function. One method employed a gastric balloon to identify DVC neurones that were responsive to gastric inflation. The second method employed a gastric vagal stimulating electrode, which permitted the identification of gastric-related NTS and DMN cells via orthodromic or antidromic activation, respectively. 4. Twenty-four of forty-two gastric-inflation-related neurones responded to administration of OT (100-400 fmol in 100-400 pl). The majority of those responding to OT were activated by this peptide (21/24). All the cells tested (n = 13) remained sensitive to gastric inflation after administration of OT. Also, OT was found to excite the majority of cells that were identified as gastric-related NTS (nine excited; one no effect) or DMN cells (eleven excited; two no effect). 5. These studies support the hypothesis that central oxytocinergic neurones influence gastric motility and secretion by increasing the excitability of central vagal neurones in the NTS and DMN that are related to gastric function. PMID- 2231435 TI - A transforming Kirsten ras oncogene in an oral squamous carcinoma. AB - This investigation has employed the NIH 3T3 cell transfection assay in an effort to detect transforming genes in DNA from squamous carcinomas of the head and neck. Of 11 tumor DNAs tested, 1 DNA sample from a gingival squamous carcinoma was able to produce primary and secondary transformants containing the human K ras oncogene. This is the first report of an activated ras oncogene derived from a carcinoma of the head and neck. Head and neck cancers may possess activated ras oncogenes more often than is indicated by this study because of the relative inefficiency of transfection assays in detecting large transforming genes such as K-ras. PMID- 2231436 TI - Effect of cannabis use on oral candidal carriage. AB - The effects of cigarette smoking on oral candidal carriage and candidosis have been well documented but few similar studies on cannabis smoking have appeared, therefore it was felt that such a study needed to be undertaken. In this investigation, the effect of cannabis smoking combined with methaqualone and tobacco on candidal prevalence, density and candidosis was examined in 55 users. Age and sex matched tobacco-smoking (n = 58) and non-smoking controls (n = 50) were examined similarly. The imprint culture technique was used for harvesting Candida. Results showed an increased prevalence and density of C. albicans in cannabis users while there was no apparent difference in the prevalence of candidiasis. However, two subjects presented with oral multifocal candidiasis. PMID- 2231438 TI - In vivo effects of Candida albicans products on rat oral epithelium. AB - Candida albicans has been associated with epithelial hyperplasia in some diseases of oral mucosa and skin but its etiologic role in these lesions is poorly understood. To test its ability to induce epithelial proliferation, the invasive hyphal form was cultured for 5 h and 23 h in chemically defined medium and yeast free culture supernatants were injected below the buccal epithelium of young adult Sprague Dawley rats. The mitotic activity was assessed using the metaphase arrest technique 11 h and 31 h after supernatant injection. There was a significant increase in epithelial mitotic activity 31 h after injection with 5 h culture supernatants compared to control media indicating that the supernatants have an effect on epithelial cells, possibly by direct action on them. PMID- 2231437 TI - Orofacial manifestations from accidental exposure to caesium 137 in Goiania, Brazil. AB - The accidental close exposure of over 200 adults and children to a caesium-137 (137Cs) source in Goiania, Brazil in 1987 produced significant short-term morbidity in about 50 patients, and four deaths within a few weeks. Some 57% of those maximally exposed to radiation, developed orofacial lesions, notably purpura, spontaneous bleeding, ulcers and/or acute candidiasis. These lesions were probably mainly the consequences of depression of bone marrow elements by the radionuclide. Though the oral lesions that may follow iatrogenic exposure to ionizing radiation are well recognized this appears to be the first report on the oral sequelae of a serious radiation accident. PMID- 2231439 TI - Additional funding for AIDS drugs. PMID- 2231440 TI - Situational instruction: teaching students with care. PMID- 2231441 TI - Your CE topic (No. 49). Breastfeeding and medications: an update (Part II). PMID- 2231442 TI - Peaceful patient. PMID- 2231443 TI - Baloney bologna. PMID- 2231444 TI - Preceptorship: socialization of students into the world of work. PMID- 2231445 TI - Bell's palsy. Signs, symptoms, outcomes. PMID- 2231447 TI - Combination intraoral and extraoral maxillofacial prostheses retained by osseointegrated implants placed in previously irradiated bone: a clinical report. PMID- 2231446 TI - Use of a sectional prosthesis following partial maxillary resection. A clinical report. PMID- 2231448 TI - Advantages and limitations in the use of porcelain veneer restorations. AB - Porcelain veneer restorations including preparations, impression materials, cast materials, refractory casts, handling of porcelain, the try-in, and the final luting are discussed. Techniques are described to increase marginal accuracy, establish predictable natural polychromatic color within the porcelain, establish good contours and surface textures, and shorten final placement time. Tooth preparation is routinely recommended, as is the combination of epoxy dies, refractory casts, and anatomic buildup techniques. Emphasis is placed on a close working relationship and communication among the dentist, dental technician, and patient. PMID- 2231449 TI - Stress distribution surrounding endodontic posts. AB - This study compared the stress distribution during insertion and function of three prefabricated endodontic posts with different designs using the criteria of post length and diameter. Test blocks of photoelastic material were prepared with simulated endodontic canals. Three posts for each design, diameter, and depth were cemented. Each specimen was examined and photographed without load, with 135 Newton (N) compressive force, and with 90 N and/or 135 N oblique force applied at 26 degrees by use of a circular polariscope. Para-Post and Para-Post Plus posts produced similar, evenly distributed patterns of stress using the criteria of diameter, depth, and load. Flexi-Post posts produced asymmetric stress patterns with concentration of stress at each thread. During compressive loading and after cementation alone, Flexi-Post posts displayed significantly higher shoulder stresses and substantially greater stresses along the coronal surface of the post's length than Para-Post and Para-Post Plus posts. Apical stresses were similar for Flexi-Post, Para-Post, and Para-Post Plus posts during compressive loading. PMID- 2231450 TI - Effect of post adaptation on fracture resistance of endodontically treated teeth. AB - This study determined the effect of different post designs and varying amounts of post-to-canal adaptation on the fracture resistance of endodontically treated teeth. Forty freshly extracted maxillary central incisors were endodontically treated. Groups of 10 teeth were prepared according to four experimental designs. Cast post and cores and crowns were waxed, cast, and luted with zinc phosphate cement on a static loading device. The teeth were embedded in acrylic resin and the crowns were loaded on a universal testing machine at 130 degrees to the long axis of the tooth until failure. Maximum adaptation of the residual root structure with a tapered post significantly increases the fracture resistance of endodontically treated teeth, but upon failure renders the tooth nonrestorable. Tapered posts resulted in fractures that were directed more apically and lingually. Parallel-sided posts had a lower frequency of fracture upon failure, involving less tooth structure. Parallel-sided posts surrounded by large amounts of cement had no significant effect on failure loads. PMID- 2231451 TI - Three-dimensional color coordinates of natural teeth compared with three shade guides. AB - The three-dimensional color coordinates of 2832 human teeth were measured in vivo and were plotted in a cylindrical Hue, Value/Chroma space, using a program in BASIC. The commonly used Vita, and Bioform shade guides, and a surviving shade guide of E. B. Clark were compared with these natural teeth. The shade guides did not match well with the color space of the human teeth, and the anticipated deficiencies were in the yellow-red Hues, higher Values, and higher Chromas. However, the points for natural teeth were in a narrow flounder-like configuration, suggesting that a representative shade guide matching natural teeth could be generated with limited samples. PMID- 2231452 TI - Occlusion for the Class II jaw relations patient. AB - Each patient with a small mandible presents an occlusal pattern that differs from most of the criteria established for a class I occlusion. The components of a class II occlusion are unlike other occlusions. The anterior teeth do not provide the protection and guidance normally provided by horizontal and vertical overlap. The posterior teeth bear the full force of occlusion. Protrusive movement is the dominant and the most used movement. The posterior teeth must function from centric relation forward to an anterior separation. Most of the posterior teeth exhibit balancing contacts. This occlusion is a type of bilateral balanced occlusion. Greater interocclusal clearance must be provided and tested for adequacy of space during speech and function. A class II occlusion is a most exacting occlusion. The controlling factors are the posterior determinants of occlusion. PMID- 2231453 TI - Prosthodontic rehabilitation of patients with Class II malocclusions. AB - The Angle's class II malocclusion patient challenges the prosthodontist because optimal treatment may include orthodontic therapy, orthognathic surgery, periodontics, and fixed or removable prosthodontics. Compromises in the treatment plan are necessary when patients cannot accept optimal dental treatment. However, specific prosthodontic principles should be observed. This article discusses Angle's class II malocclusions, including the theories and therapies to treat patients with this malrelationship successfully. Prosthodontic management of the malocclusion is an adjunct to other care rendered. PMID- 2231454 TI - Clinical implications of the response of enamel and dentin to masticatory loads. AB - The success of restorative procedures is dependent on comprehension of the responses of enamel and dentin, including responses to masticatory forces. The regional variation resulting from masticatory forces is critical because clinically it relates to the thickness of enamel and dentin occlusogingivally. Three-dimensional finite element models of an intact mandibular molar were developed to analyze stresses in enamel and dentin occlusogingivally, buccolingually, and mesiodistally. There were dramatic regional variations in the magnitude and character of different stresses caused by masticatory forces, and despite being organically "bonded," enamel and dentin responded independently. This unique behavior with regional variations of these tissues could have serious clinical implications during restorative procedures. PMID- 2231455 TI - Temperature changes during the finishing of amalgam restorations. AB - The finishing and polishing of amalgam restorations may be harmful to the pulp because of the heat generated during these procedures. In this study, changes in temperature of the pulp in extracted teeth were determined in vitro. During the polishing procedure, a variety of instruments were used under a variety of circumstances: with or without a water coolant, intermittent or continuous operation, high or low rotation speed, and high or low pressure. Finishing or polishing without a water coolant always increased the temperature of the pulp. When the pressure was high, during continuous polishing, or during a higher velocity of rotation, pulpal temperatures increased more than 20 degrees C within 30 seconds. However, when a water coolant was used, a decrease in the temperature was always observed. Procedures carried out with low pressure showed a decrease in the pulpal temperature of approximately 9 degrees C. High pressure decreased the temperature of the pulp by only 4 degrees C. Therefore a water coolant is always advised when amalgam restorations are being finished and polished. PMID- 2231457 TI - Gravity-induced stresses by an obturator prosthesis. AB - Recontruction after surgical resection of tumors of the maxillae and paranasal sinuses is difficult. In addition to the intermittent forces encountered during function, the prosthesis is subjected to the constant force of gravity. This investigation photoelastically studies the gravity-induced stresses transmitted to the remaining oral structures by various obturator prosthesis framework designs. Frameworks which used I-bar and circumferential retainers with buccal retention were most severe, while the swinglock and light wire retainers were intermediate in generated stress. PMID- 2231456 TI - A study of the importance of the neutral zone in complete dentures. AB - Mastication, comfort, and speech were determined and compared for patients using conventional complete dentures and dentures made with the neutral zone concept. PMID- 2231458 TI - Modification of osseointegrated implants for distal-extension prostheses. AB - The use of a distal implant abutment splinted to a natural tooth by a fixed partial denture has been employed for distal-extension prostheses. There is a differential difference between the viscoelastic deflection of a natural tooth by its periodontal ligament, and the almost negligible elastic deformation of an osseointegrated implant. This difference may induce a fulcrum-like effect and overstress the implant. In this study a new modification of osseointegrated implants was proposed to counteract this problem. This modification was achieved by using a resilient layer material under the superstructure of the implant. Finite element modeling (FEM) was used to examine stresses and displacement distribution around a commercially available implant and one experimental implant with a resilient layer material. The results of this study showed that the new modification is a simple and efficient way to mimic the structural natural tooth unit. It also showed that it allowed movement of the superstructure without movement of the implant three times that of the nonresilient model. PMID- 2231459 TI - A survey of dentists practicing implant dentistry in Israel. AB - Due to the increasing interest in the field of implant dentistry, a first survey of dentists in Israel who used implants was conducted. Out of a total of 312 dentists questioned, 97 reported using dental implants in their practice. In spite of the team approach advocated in the literature, 40% of the dentists in the survey conducted both the surgical and the prosthetic phases of treatment. Over 60% of the respondents had less than 3 years' experience in the field, which is in keeping with the worldwide trend. A smaller number than expected regarded red gingival color and bone resorption based on radiographic findings as grounds for implant failure. In the view of at least 10 respondents, pain, discomfort, exudate, and fistulization did not indicate unsuccessful implants. A disparity was revealed between the dentists' practice methods and their hypothetical choice of self-treatment. Although the Core-Vent method was the most widely employed, only 50% of those using this system preferred it for themselves. Even fewer (25%) of those using blade implants considered it their self-treatment of choice. In contrast, although only 10% of the dentists had used the Branemark method, 30% preferred it for their own treatment. PMID- 2231460 TI - Anterior guidance: group function/canine guidance. A literature review. AB - Anterior guidance, which can be categorized as group function or canine guidance, is essential for esthetics, phonetics, and mastication. This article reviews the historical development and philosophies of both occlusal schemes. There is no scientific evidence that supports one occlusal scheme over the other. Where anterior guidance must be reestablished or where it changes, there currently appear to be more authorities who favor canine guidance over group function. PMID- 2231461 TI - The rotational aspect of mandibular flexure. AB - A rotational aspect to mandibular flexure has been demonstrated by means of photographic comparisons. The importance of this movement in relation to anatomic considerations, periodontal therapy, restorative dentistry, and implant-supported prostheses, is discussed. PMID- 2231462 TI - Psychologic facets of esthetic dental health care: a developmental perspective. AB - A developmental perspective is presented to explore dental health and esthetics in dentistry and to describe the specific ways human behavior and various aspects of esthetic health care interrelate. An investigation of the fascinating links between mind and mouth over the life cycle are elucidated to explain how and why the oral cavity is so psychologically important. Clinical examples of how personality factors can influence dental treatment and its outcome are illustrated. PMID- 2231464 TI - Dental laboratory work authorization forms: a survey. AB - Dental laboratory work authorization forms embrace a diversity of material content and design. This survey examined 51 dental laboratory work authorization forms and delineated each content item and format features into a frequency percentage. This information has a high potential for use in changing prospective dental laboratory and authorization form design. PMID- 2231463 TI - Effect of retention grooves on tooth-denture base bond. AB - The bond strength of acrylic resin teeth with and without retention grooves processed onto standard and high-impact denture base resin was investigated. A shear compressive force was applied at an angle of 130 degrees to the lingual surface of the teeth until fracture occurred. The values were subjected to a two way analysis of variance with repeated measures. Canine teeth bonded better than central or lateral incisors (p less than 0.01). A significantly greater force was required to fracture teeth from high-impact resin (p less than 0.01). Vertical retention grooves enhanced bond strength (p less than 0.01). PMID- 2231465 TI - A prosthesis to control microstomia. PMID- 2231466 TI - Mesiolingual amalgam rest seat for a mandibular canine. PMID- 2231467 TI - The diagnosis of extracapsular craniomandibular disorders. PMID- 2231468 TI - The effect of powder/water ratio of irreversible hydrocolloid on the bond strength of irreversible hydrocolloid and agar combinations. PMID- 2231469 TI - A provisional and new crown to fit into a clasp of an existing removable partial denture. PMID- 2231470 TI - Experimental studies on thallium toxicity in rats. II--The influence of several antidotal treatments on the tissue distribution and elimination of thallium, after subacute intoxication. AB - The influence of several antidotal treatments--e.g. Prussian Blue + Furosemide, Furosemide, activated Charcoal, Potassium Chloride and Potassium Iodide--on the tissue distribution and elimination of thallium after subacute intoxication is studied. From these experiments, the fate of electrolytes (Na+, K+, Cl-) may be evaluated. It was established that the efficacy of an antidotal treatment in thallium intoxication may be judged not only by the determination of its ability to interfere in the reabsorption and redistribution of thallium. Prussian Blue was the only antidotal that did not cause such a dangerous redistribution. PMID- 2231471 TI - [The anti-implantation effects of various savine extracts on the pregnant rat]. AB - Ether and ethyl acetate extracts obtained after savin essential oil extraction, were administered, on days 1 to 4, to pregnant rats by intragastric catheter, at doses of 0, 50 or 150 mg/Kg, to search for their possible effects on implantation. The ethyl acetate extract was not toxic. Inversely, the ether extract was responsible for a dose-dependent anti-implantation effect, thus showing that essential oil is not alone responsible for the abortive effect generally attributed to Savin. PMID- 2231472 TI - [Phenytoin and the popliteal lymph node test in the Sprague-Dawley rat]. AB - The detection of xenobiotics which the potential to induce autoimmune reactions is currently hardly possible. The popliteal lymph node assay initially developed in mice may prove useful in this regard. Results obtained with phenytoin in Sprague Dawley rats are presented. Single doses of phenytoin were injected into one hind footpad and the popliteal lymph node was excised and weighed 3, 7 or 10 days after injection. Only the 5 mg dose level produced a significant increase in popliteal lymph node weight, structural and cellular changes in the lymph node indicating a humoral stimulation was noticed in the males at 2 mg and in the males and females at 5 mg. These results warrant further progress in the development of this assay. PMID- 2231473 TI - [The Stevens-Johnson syndrome from maprotiline and propranolol?]. AB - A wide variety of agents have been associated with erythema multiforme, particularly drugs and infectious agents. We describe a typical Stevens-Johnson's syndrome developing 15 days after initiation of propranolol and maprotiline therapy. Other etiologies have been excluded by appropriate investigations and the responsibility of each drug is discussed. PMID- 2231475 TI - Functional correlates of characteristic frequency in single cochlear nerve fibers of the Mongolian gerbil. AB - Single-unit recordings obtained from the auditory nerve of the Mongolian gerbil, Meriones unguiculatus, revealed functional differences in the response properties of neurons tuned to low and high frequencies. The distribution of neural thresholds displayed a distinct rise for auditory nerve fibers with characteristic frequencies (CFs) between 3-5 kHz. This frequency band also marked abrupt changes in both the distribution of spontaneous discharge rates and the shape of the neural tuning curve. For neurons of all CFs, spontaneous firing rates were inversely related to neural threshold but unrelated to sharpness of neural tuning. The range of CF thresholds encountered, even when data from many animals were combined, rarely exceeded 20 dB, suggesting that cochlear nerve responses obtained from this species display little inter-animal variability. These results are compared with similar data from other species and discussed in terms of recent studies on sound communication and cochlear anatomy in gerbils. PMID- 2231474 TI - Olfactory interneurons in the brain of the larval sphinx moth Manduca sexta. AB - 1. The physiology and morphology of olfactory interneurons in the brain of larval Manduca sexta were studied using intracellular recording and staining techniques. Antennal olfactory receptors were stimulated with volatile substances from plants and with pure odorants. Neurons responding to the stimuli were investigated further to reveal their response specificities, dose-response characteristics, and morphology. 2. We found no evidence of specific 'labeled-lines' among the odor-responsive interneurons, as none responded exclusively to one plant odor or pure odorant; most olfactory interneurons were broadly tuned in their response spectra. This finding is consistent with an 'across-fiber' pattern of odor coding. 3. Mechanosensory and olfactory information are integrated at early stages of central processing, appearing in the responses of some local interneurons restricted to the primary olfactory nucleus in the brain, the larval antennal center (LAC). 4. The responses of LAC projection neurons and higher order protocerebral interneurons to a given odor were more consistent than the responses of LAC local interneurons. 5. The LAC appears to be functionally subdivided, as both local and projection neurons had arborizations in specific parts of the LAC, but none had dendrites throughout the LAC. 6. The mushroom bodies and the lateral protocerebrum contain neurons that respond to olfactory stimulation. PMID- 2231476 TI - Analysis of associative learning in the terrestrial mollusc Limax maximus. II. Appetitive learning. AB - The odor and taste processing systems of the terrestrial mollusc Limax maximus have been shown capable of a number of complex computations. Most of the complex higher-order features of Limax learning have been demonstrated using differential aversive conditioning. The present experiments probe the appetitive learning ability of Limax. In the first experiment a differential appetitive classical conditioning procedure was used. An aversive CS+ odor was paired with an attractive taste while a CS- odor was explicitly unpaired with the attractive taste. This appetitive conditioning procedure dramatically increased the preference for the CS+ odor. Further experiments determined the time course of acquisition, the effect of an extinction procedure and long-term retention of the appetitive conditioning. Now that Limax has been shown capable of appetitive conditioning, the neural network simulation of Limax learning, called LIMAX, can be examined for its ability to display appetitive conditioning. PMID- 2231477 TI - Evoked pre- and post-synaptic activity in the optic tectum of the cannulated tadpole. AB - We describe the cannulated Rana pipiens, tadpole preparation that allows for stable recording in the tectum of the extracellular potential elicited by optic nerve stimulation. The largest components of the evoked tectal response consist of two previously identified waves and a major third, long-latency wave of long duration. These components were reversibly eliminated by perfusion of high magnesium/no calcium Ringer's solution or Ringer's solution containing cobalt chloride. In contrast, perfusion of high calcium/no magnesium Ringer's increased the amplitude and area of these components. We conclude that these components represent post-synaptic activity. Additionally, small, short-duration waves were identified as arising from the activity of retinal afferents. They consisted of a short-latency (3.1-7.6 ms) and a long-latency (12-23 ms) group. Waves belonging to both of these classes were still visible in both high magnesium/no calcium Ringer's solution or Ringer's solution containing cobalt chloride and were unaffected by high calcium/no magnesium Ringer's. The average conduction velocities of the short- and long-latency groups matched the conduction velocities of, respectively, edge and convexity detectors in the adult. This indicates that retinal afferent input may already be present in adult patterns at the time that tectal circuitry is developing. PMID- 2231478 TI - Reference in single sentences and in texts. AB - This study investigated the comprehension and production of reference terms in both sentences (Experiments 1 and 2) and texts (Experiments 3 and 4) using a sentence completion task. In Experiments 1 and 2, the use of a sentence-level strategy (subject assignment) was investigated. In Experiments 3 and 4, the use of a text-level strategy (topic assignment) was also investigated. There was a clear preference for continuing the sentences by referring to the subjects of the sentences regardless of the availability of gender cues, in both single sentences and in texts. There was also an influence of the topic of each text on both the choice of referent and the type of reference term used. However, the choice of reference term was affected by the number of potential antecedents in the preceding text. Overall, the results suggest that the sentence subject is a salient item in working memory. This salience is increased if the sentence subject is also the textual topic. In addition, it appears that the presence of a pronoun in a text triggers a specific strategy to assign the pronoun to the (salient) sentence subject. PMID- 2231479 TI - Conversational time patterns and mutual influence in parent-child interactions: a time series approach. AB - Mutual influencing processes are assumed to be the basic building blocks in establishing parent-child bonding and in influencing cognitive and language behavior. A study by Jasnow and Feldstein (1986) revealed that, within the temporal domain of speech, preverbal (9-month-old) infants and their mothers exhibit a pattern of mutual influence (attunement) in their average durations of switching pauses. The general purpose of this research was to extend those findings to children with higher verbal functioning. In addition, parent and child genders, nature of the interaction, and specific aspects of parents' personalities, expressiveness, and instrumentality were considered. Each parent interacted with their 4- or 5-year-old son or daughter in each of two conversations--unstructured (social conversation) and structured (task activity). Conversations were processed by an automated computer system yielding objective measure of turns, vocalizations, pauses, and switching-pause durations. To examine interspeaker influence of attunement of temporal speech patterns, "influence coefficients" were computer for each speaker on a "turn-by-turn" basis using time series regression. Analysis of these coefficients revealed that: (1) Mutual influence is most evident with switching-pause duration. (2) Structure in the conversation (as defined by the task or parental instrumentality) seems to facilitate attunement for vocalization and switching pause duration. (3) Attunement with girls seems to occur equally well with both parents, while boys exhibit a style of temporal patterning influence which suggests greater identification with the father. (4) Expressiveness seems to facilitate attunement to the child's switching-pause duration. PMID- 2231480 TI - The use of heuristic strategies in the interpretation of pronouns. AB - The aim of the two experiments reported here was to distinguish between two heuristic strategies that have been proposed to account for the assignment of pronouns: the subject assignment strategy and the parallel function strategy. According to the subject assignment strategy, a pronoun is assigned to a preceding subject noun phrase, whereas according to the parallel function strategy, a pronoun is assigned to a previous noun phrase in the same grammatical position as the pronoun. These two strategies were tested by examining the interpretation of single object pronouns, first in a reading task and second in an assignment task. In both experiments, there was a strong preference for assigning an object pronoun to the preceding subject noun phrase, thus supporting the subject assignment strategy. However, this was only the case for pronouns that were linguistically ambiguous. When assignment was constrained by gender, there was no effect of either strategy. It is suggested that heuristic strategies are only used in the absence of other strong cues to assignment. PMID- 2231481 TI - Physical symptom severity, psychological and social dysfunction in a series of outpatients with irritable bowel syndrome. AB - Details of physical symptoms, psychological and social dysfunction of 42 outpatients diagnosed as having irritable bowel syndrome (IBS) were collected by interview and questionnaire. Social stresses and problems were also elicited as well as the impact of symptoms on their subjects' daily lives. High proportions of subjects were handicapped in their social, sexual and working lives by IBS symptoms and social stresses and problems were common. Forty-eight per cent were classified as having a 'minor psychiatric illness' using the Clinical Psychiatric Interview. Women were more severely affected by physical symptoms (with the exception of diarrhoea) and were more likely to be in pain longer and for more days in the month. They were also more likely than men to be diagnosed as having a psychiatric illness. PMID- 2231482 TI - Effects of temporary withdrawal from regular running. AB - Forty regular male runners were divided into two similar groups and studied for six weeks. One group continued normal running, but the other stopped running for the middle two weeks of the study. Questionnaires were completed at the end of each week. Symptoms of depression were greater in the withdrawn than in the control group at the end of the second week of withdrawal. Somatic symptoms, anxiety, insomnia and feelings of being under strain were greater in the withdrawn group after both the first and second weeks of withdrawal. The groups did not differ in the final two weeks, when running had been resumed. These effects strengthen the view that stopping regular physical exercise produces a 'withdrawal syndrome', and that exercise might therefore be regarded as addictive. The increase in depression may reflect a more gradual loss of the antidepressive effect of exercise training. PMID- 2231483 TI - Cultural factors in the eating disorders: a study of body shape preferences of Arab students. AB - A replication of an American study of body shape preference was conducted in a group of 218 Arab students attending the American University in Cairo, Egypt. Arab female students felt their ideal shape to be significantly thinner than their current shape, while male students did not. Hence the appraisal of body shape shows gender differences in Egypt consistent with the American study. The Arab women reported a current shape similar to American women but had a smaller discrepancy between ratings of their ideal and current body shape. There was no difference for either Arab women or men between the shape thought most attractive to the opposite sex and that which the other gender actually reported as most attractive. The study shows a clear preference for thinness in the Arabic culture, inferences are made to its role in predisposing to eating disorders. PMID- 2231484 TI - Motivational factors in women requesting augmentation and reduction mammaplasty. AB - This study confirms that women requesting breast reduction and breast augmentation differ beyond the anatomical. There were significantly more single and co-habiting women in the breast reduction group, and significantly more separated and divorced women in the breast augmentation group, compared to women attending an obstetric clinic. The majority of women requesting surgery agreed that to feel more confident was an important reason for seeking surgery, but those requesting breast augmentation also stressed the need to feel more feminine and less shy with men. A significantly higher percentage of the breast augmentation group had been pregnant, and they had a higher average number of pregnancies than the obstetric comparison group, together with a significantly higher experience of miscarriage. The psychodynamic proposal that women requesting breast augmentation are seeking to symbolically boost their sense of femininity and womanliness is supported by this study. PMID- 2231485 TI - Education, lifestyle and arterial blood pressure. AB - Lower education is associated with higher blood pressure and mortality from cardiovascular disease. Reasons for this are explored in this paper. It is hypothesized that education is most important as a risk factor for high blood pressure to the extent that an individual's style of life is incongruent with his or her education. Style of life is defined here on the basis of the accumulation of consumer goods and exposure to mass media. It was found, in a study of blood pressure in an African-American community, that lifestyle incongruity, or the degree to which style of life exceeded education, was associated with higher systolic and diastolic blood pressure, adjusting for age, sex, Body Mass Index, income, chronic social stressors, and Type A behavior. It is argued that this incongruity leads to recurring frustrating social interactions, which in turn are related to higher blood pressure. PMID- 2231486 TI - Sex differences in general practice attendance and help seeking for minor illness. AB - Women's rates of utilization of almost all health care services are higher than men's. General practice surveys endorse these findings with women attending more frequently, particularly in the child bearing years. The present study sought to explore the variables associated with consultation and help seeking behaviour for minor illnesses. Samples of male and female low and high attenders aged between 20 and 45 were drawn from one general practice to investigate which factors were important in explaining sex differences in consultation. Analysis of the results suggests that attendance and help seeking in men and women was closely linked to physical illness, the presence of physical symptoms was predictive of more frequent consultation in both men and women. The presence of psychosocial problems or distress, however, predicted consultation behaviour in women but not in men. The women had more confidants and contacted more social agencies than the men, also suggesting that they found it easier to divulge personal information to others than the men. There was no evidence from this study that such enabling factors as physical accessibility and time available were related to differential attendance rates. PMID- 2231487 TI - Insulin-dependent diabetes mellitus: a risk factor in anorexia nervosa or bulimia nervosa? An empirical study of 116 women. AB - A number of recent studies suggest that diabetes mellitus confers a high risk for the development of anorexia nervosa or bulimia nervosa. In order to test this hypothesis, 56 women with IDDM and 60 non-diabetic female controls were studied. All subjects completed the Eating Attitudes Test (EAT), and the Bulimic Investigatory Test, Edinburgh (BITE). The subjects were interviewed in order to obtain clinical and demographic information as well as to determine test validity. The DSM-III-R criteria of anorexia nervosa and bulimia nervosa were used. Four items were removed from the original EAT in order to eliminate possible bias related to IDDM. The results did not support the hypothesis that eating disturbances occur more frequently in IDDM-patients. Six criteria are proposed to improve the methodological standards of future studies in order to facilitate comparison of results. PMID- 2231488 TI - The treatment of tension headache by acupuncture: a controlled single case design with time series analysis. AB - A single case design, with time series analysis, was employed to evaluate the efficacy of acupuncture in the treatment of tension headache. Fourteen patients were given eight weekly treatments, four of true acupuncture and four of sham in random order. Mean pain in medication scores were reduced by 52% and 54% respectively at initial follow-up. Reductions in pain scores of over 50% were achieved by half the patients and the significance of these changes confirmed by time series analysis. The majority of patients maintained their gains at four month follow-up. True acupuncture was shown to be significantly superior to sham, demonstrating a specific therapeutic action, in four patients. In the remainder no difference was observed. Possible mechanisms for these effects are discussed. Acupuncture is a potentially valuable treatment for tension headache but further research is needed. PMID- 2231489 TI - The functional role of exercise in the development of weight and diet concerns in women. AB - The functional role of exercise in the development of weight preoccupation and body dissatisfaction was examined. One hundred and twelve females, identified as regular participants in exercise programmes, completed an inventory that provided information on attitudes, behaviours and psychological characteristics related to dieting and weight-control, as well as a self-report of physical activity. A structural equation model was tested that provides support for the notion that Body Mass Index, emotional reactivity and physical activity have statistically significant direct effects on weight and diet concerns, but that weight and diet concerns do not predict the degree of participation in physical activity. Significant differences in eating disorder indicators were found between sub groups identified as 'constantly dieting' and 'rarely dieting'. The tentative, but important, conclusion was drawn that regular participation in a fitness programme may be causally related to excessive concern with weight and dieting. PMID- 2231491 TI - The negative correlations between Type A behavior and somatic risk factors of coronary heart disease (CHD) in adolescent boys. PMID- 2231490 TI - Cardiovascular responses to behavioral stressors: laboratory-field generalization and inter-task consistency. AB - Blood pressure and heart rate responses were monitored while 30 medical, dental or graduate students completed four laboratory tasks. On a second day, subjects wore an ambulatory blood pressure monitor, and during this day they completed the real-world challenge of presenting their research in front of a small audience. Heart rate and blood pressures correlated significantly between all four laboratory tasks for both absolute levels and reactivity scores (calculated as task level minus pre-task baseline level). However, while heart rate and blood pressure absolute levels for each task correlated significantly with those attained during the real-world stressor, correlation coefficients obtained when similarly comparing reactivity scores were uniformly non-significant. Laboratory field generalization was thus evident only for absolute values. Consideration was then given to the fact that the laboratory tasks were undertaken in a seated position, while subjects stood during the real-world task. Activity diaries completed by subjects during the time they wore the ambulatory monitor were examined to search for readings that could be regarded as standing baselines. Such values were obtained for 12 of the subjects. Real-world reactivity scores were recalculated using these standing baselines, and compared again with reactivity scores during the laboratory tasks. Marked increases in correlation coefficients were obtained for systolic and diastolic pressure, but not for heart rate. PMID- 2231492 TI - What's new in orthopaedic surgery. PMID- 2231493 TI - Progress in the assessment of liver blood flow in health and disease. AB - Several of the reasons why the liver is a vital organ are illustrated in this review. The fundamental importance of its dual arterial and portal venous supply is shown in a wide range of physiological and pathological conditions, ranging from digestion to regeneration, cirrhosis, mesenteric ischaemia and malignancy. In most, if not all, of these functions the blood supply exerts an important, if not prime, role. This article reviews some of the progress made in evaluating these vital hepatic circulatory phenomena. PMID- 2231494 TI - Risk factors in patients with ischaemic rest pain of the lower limbs. AB - One hundred and three consecutive out-patients with ischaemic rest pain were studied. There were 77 men and 26 women with a mean (s.d.) age of 71 (10) years. Thirty-six (35.0%) patients had rest pain alone, 41 (39.8%) in association with an ischaemic ulcer and 26 (25.2%) with digital gangrene. A significantly increased risk of amputation was seen in those patients with an elevated serum cholesterol (greater than 5.2 mmol/l; P = 0.01), white blood cell count of greater than 10 x 10(9)/l (P = 0.05), fibrinogen greater than 4g/l (P = 0.04), and in women with elevated triglyceride levels (greater than 1.8 mmol/l; P less than 0.03). An increased risk of death for all patients was also associated with elevated triglyceride levels (P = 0.03). Few of the women smoked (P less than 0.0004), but they were more likely to have suffered a stroke (P = 0.01). They also had a significantly increased cholesterol level (P = 0.03) and tended to have a higher mortality rate than the men (P = 0.08). Surprisingly, smokers did not have a significantly higher amputation or death rate than non-smokers. Elevated plasma viscosity, packed cell volume, platelet count, haemoglobin and creatinine levels were not independent risk factors for any group. At 30 days after presentation the limb salvage rate was 73% (75/103), amputation was required in 15 (14.6%) cases and 13 (12.6%) patients died. Patients with ischaemic rest pain constitute a heterogeneous group with multiple diseases and risk factors. Early identification and treatment of risk factors may help to improve limb salvage and the mortality rate in this condition. PMID- 2231495 TI - Repair of coronal and subcoronal hypospadias: an 8-year retrospective study. AB - Twenty-three patients undergoing treatment for coronal and subcoronal hypospadias over an 8-year period were reviewed. A ventral skin tube inlay graft was used in all cases, and a comparison made between Nesbitt's button hole technique and three other procedures used for ventral skin cover. The button hole procedure was associated with fewer fistulae and provided acceptable cosmesis. PMID- 2231496 TI - Primary gastrointestinal non-Hodgkin's lymphoma: a study of 35 patients. AB - In a retrospective study of 35 patients (29 men, 6 women) with primary non Hodgkin's lymphomas of the gastrointestinal tract, 13 of the tumours were located in the stomach, 21 in the small bowel and one in the colon. Various radiological findings were detected, and the majority of tumours (23) had high grade histology. Three patients had immunoproliferative small intestinal disease. Only tumours in stages I and II were included in the study, and the majority (25) were in stage IIA. All patients except one had undergone resection of the neoplasm. This was followed by combined chemotherapy in 25 patients, and chemotherapy followed by radiotherapy in three cases. There were two (5.7%) hospital mortalities. Two- and 5-year survival rates were better in those patients with low stage and low grade tumours. The overall 5-year survival rate was 38%. PMID- 2231497 TI - Early gastric cancer: a report of 30 cases. AB - Thirty patients with early gastric cancer have been reviewed. Endoscopy demonstrated gastric abnormality in 93% of patients examined and biopsy was accurate in 96% of cases. Twenty-nine patients were treated by partial gastrectomy, although three required further procedures. The commonest morphological type was type III (45%). Five patients with early gastric cancer had lymph node spread at the time of presentation. The relative 5-year survival rate was 68%. Four patients eventually died of gastric cancer. Three patients (10%) developed a second primary carcinoma. The significance of this diagnosis is emphasized and selective screening is considered. PMID- 2231498 TI - Bacterial colonization of the skin after chemical depilation. AB - A study of the effects of preoperative skin depilation on skin microflora has been performed. Areas of skin were prepared with a chemical depilatory agent and compared with areas of unprepared skin. Preparation of skin with a chemical depilatory agent causes no increase in skin microflora, in contrast to the effects of shaving as demonstrated by earlier studies. PMID- 2231499 TI - Grafting without a donor site: an easy approach to pretibial lacerations. AB - Pretibial lacerations are a common soft tissue injury especially amongst elderly women. An alternative repair approach to this problem is described. The traumatized and often necrosed-looking flap of skin from the injured area is made into a full thickness 'fenestrated' skin graft to cover the defect. Experience of 30 cases shows the method to be useful for accident and emergency departments as well as surgical units. The healing time is shorter than in conservative methods and similar to 'meshed split skin grafting' as an out-patient procedure, but the great advantage is the absence of a donor site. PMID- 2231500 TI - Early experience with reconstructive surgery at Mpilo Central Hospital, Zimbabwe. AB - A total of 46 patients were admitted to Mpilo Central Hospital for various reconstructive procedures between August 1988 and February 1989. The majority of patients had postburn contractures, i.e. 18 cases (39%). The rest of the patients were admitted for treatment of bed sores (nine cases, 20%), keloids (nine cases, 20%), post-traumatic complex soft tissue defects (five cases, 11%), lower lip defects following a human bite (three cases, 6%) and complex lesions on the face (two cases, 4%). Although a few complications were encountered the results overall were very good. There was no mortality recorded in this series. PMID- 2231501 TI - Spontaneous duodenocolic fistula. PMID- 2231502 TI - Fatal clostridial pancreatitis following transduodenal biopsy of the pancreas. PMID- 2231503 TI - Surgery in Singapore--the Scottish link. PMID- 2231504 TI - Ten-year experience of bone and joint tuberculosis in Blackburn 1978-1987. AB - A retrospective review of 70 cases of bone and joint tuberculosis seen between 1978 and 1987 is reported. Forty-nine of the cases were patients of Indian subcontinent ethnic origin. There was a wide range of sites affected. Pain, swelling or sinus formation were the commonest presenting features. Delay in diagnosis from the first hospital visit was significantly longer in the Caucasian population (mean delay; Caucasian 17.6 weeks, Indian subcontinent 2.8 weeks). Drug treatment was used in all cases, combined with biopsy in 21 cases and more radical surgery in 28 cases. The results of treatment were good with low morbidity and mortality, long-term problems have been few, and no relapses have occurred. Nine months of chemotherapy and the joint system of orthopaedic and medical management employed locally are strongly recommended. PMID- 2231505 TI - Eikenella corrodens osteomyelitis of the spine. PMID- 2231506 TI - Humeral shaft fracture and arm-wrestling. PMID- 2231507 TI - Fracture-dislocation of the cervical spine: complication of traditional Zulu dancing. PMID- 2231508 TI - Locking of the metacarpophalangeal joint. PMID- 2231509 TI - Role of surgery in the treatment of pseudomyxoma peritonei. PMID- 2231510 TI - Obstructing carcinoma of the left colon managed by subtotal colectomy. PMID- 2231511 TI - Extrahepatic biliary cystadenoma: report of a case and review of the literature. PMID- 2231512 TI - Primary adenocarcinoma of the appendix. PMID- 2231513 TI - Changes in the incidence of medical conditions at the Commando Training Centre, Royal Marines. PMID- 2231514 TI - A narcoleptic in the Navy. PMID- 2231516 TI - The management of heat illness. PMID- 2231515 TI - Resuscitation box--what do I put in M88? PMID- 2231517 TI - The neurological sequelae to toluene inhalation. PMID- 2231518 TI - An outbreak of 'flu. PMID- 2231519 TI - Operating at sea in an aircraft carrier. AB - The policy of the Medical Officers serving in HMS Ark Royal between January 1988 and June 1989 with regard to surgery and anaesthesia at sea is described. The skills and equipment available, techniques used, operations performed and complications that resulted are outlined. The advantages and disadvantages of an active operating policy are discussed and the postulate ventured that in order to achieve maximum efficiency within the medical department of an aircraft carrier such a policy is justified. Finally, in the light of present day litigious trends, the question of the propriety of the policy is posed. PMID- 2231520 TI - NBCI--another threat to operational effectiveness? AB - Battle casualties are well recognised as a threat to Operational Effectiveness (OE) at times of conflict. Less well appreciated is that naturally occurring illnesses and injuries--Non-Battle Casualties and Injuries (NBCI)--continue to present at such times and will add to the problems of fighting the ship. This prospective study showed that NBCI resulted in a total of 1369 man days of lost personnel effectiveness among some 1738 RN servicemen during a 180 day deployment. That is just 0.42% of the possible man working days. This represents a loss of 4.3 man days per 1000 at risk per day in terms of fitness for Full Duties or 2.74/1000/day excluding those able to perform Light Duties. It is unlikely that such rates would affect the OE of the fighting units but they do represent a significant challenge to the Royal Naval Medical Service to continue to maintain the rates at such low levels, so that when aggregated to the numbers of battle casualties, OE is maintained as far as possible. PMID- 2231521 TI - The effect of clothing on the initial responses to cold water immersion in man. AB - The protection provided by three clothing assemblies against the cold shock response was investigated. Nine healthy male volunteers each undertook three two minute head-out immersions into stirred water at 10 degrees C. The subjects wore a different clothing assembly for each immersion, these were: a) Swimming trunks only; b) Conventional clothing (equivalent to RN No 8s); c) Conventional clothing plus windproof/shower-proof clothing (RN foul-weather clothing Mk III). The cardiac, ventilatory and thermal responses of the subjects were examined before and during the immersions. No significant differences were found between the magnitude of the responses recorded on immersion when conventional clothing or foul-weather clothing were worn. Mean skin temperature was lower (P less than 0.05) and respiratory frequency and minute ventilation were higher (P less than 0.05) on immersion in swimming trunks compared to the other two conditions. It is concluded that when policies for the use of immersion protective clothing are being formulated, consideration should be given to all of the potentially hazardous responses associated with cold water immersion. PMID- 2231522 TI - The fluorosis risk index: a method for investigating risk factors. AB - The fluorosis risk index (FRI), a new index developed for use in analytical epidemiologic studies, is designed to permit a more accurate identification of associations between age-specific exposures to fluoride sources and the development of enamel fluorosis. The FRI divides the enamel surfaces of the permanent dentition into two developmentally related groups of surface zones, designated either as having begun formation during the first year of life (classification I) or during the third through sixth years of life (classification II). Data from the first use of this index in a population-based case-control study are given to illustrate the high reliability of the index, its validity, and its unique utility for the identification of risk factors of enamel fluorosis. PMID- 2231523 TI - Caries prevalence in Head Start children, 1986-87. AB - Since the early 1970s, caries prevalence among school-aged children in the United States has declined. It appears that a small percentage of the children experience most of the caries increment. In addition, a large proportion of children in the US who need dental care receive it. An important factor in the amount of treatment received by children is the socioeconomic status of the family. Data on caries prevalence among preschool populations are limited. The Head Start program serves low-income families in the US and offers a unique opportunity to look at individuals who may be at greater risk of health problems and may experience less access to health services. A survey of 1,796 three- to five-year old Head Start children from low-income families was conducted in 1986 87. Caries prevalence, baby bottle tooth decay prevalence and relative need for dental care are reported for fluoridated and non fluoridated communities in California, Hawaii, and Micronesia. The data reveal scores that are higher in the sample population than in five-year-olds in national surveys and among Head Start children in previous surveys. PMID- 2231524 TI - Infection control in the Indian Health Service Dental Program: estimated costs and effects on productivity. AB - The dental literature contains many recommendations defining standards for infection control. Little information is available, however, documenting the cost of implementing these standards. This article describes the cost incurred by the Indian Health Service Dental Program in the Oklahoma area between 1985 and 1988 for infection control. During this period, comprehensive infection control recommendations were published for oral health programs serving Native Americans and data were collected on supply utilization. While productivity data were collected for that same time period do not support the premise that infection control practices lead to decreased clinical productivity, infection control supply costs did increase over fourfold during this period. PMID- 2231525 TI - Patterns of sealant delivery under variable third party requirements. AB - Despite evidence indicating dental sealants to be effective in preventing caries on the pit and fissure surfaces of teeth, only 8 percent of school-aged US children had received sealants as of 1986-87. While many rationales have been suggested and scientifically answered for this low level of utilization, issues of cost and cost effectiveness remain considerable barriers to many insurers and public programs. This study reports dentist behavior when sealants were added with few restrictions as a new benefit to an existing third party system of care. Results are compared to another third party program with stricter reimbursement policies. Overall, sealants were provided in a reasonable fashion to both groups of patients, relative to teeth selected for sealing and costs. Only a small proportion of patients receiving sealants were under age six or above age 19. Even under the most liberal program, sealants were predominantly targeted to teeth at highest risk to decay. Still, for both groups, a significant proportion of the sealants were placed in teeth at points in time quite distant from expected eruption patterns and, thus, their periods of highest risk to decay. Overall, dentists appeared to use sealants only minimally in their practices. These data suggest that sealants can be added to third party dental programs with little overall risk of inappropriate use or abuse. They also suggest that specific efforts are merited to educate providers as to the most effective times at which to provide sealants for preventing the maximum amount of decay in a population. PMID- 2231526 TI - A fluoridation campaign: the Phoenix experience. AB - On January 31, 1989, the city council of Phoenix, Arizona, voted to approve water fluoridation. Despite a small number of campaign participants and a limited budget, profluoridationists launched a successful 16-month effort that included novel marketing techniques, intensive collaboration with media representatives, and an aggressive challenge of the antifluoridation movement. Public support was garnered through an advisory petition effort and positive media coverage; political support resulted from a carefully orchestrated educational strategy that included expert testimony and comprehensive reference materials. With a population of approximately 1 million people, Phoenix is the ninth largest city in the country and, until the measure was implemented, the third largest nonfluoridated city. PMID- 2231527 TI - Workshop to Develop Competency Objectives in Dental Public Health. Proceedings. American Association of Public Health Dentistry Ad Hoc Committee to Update the Behavioral Objectives in Dental Public Health. PMID- 2231528 TI - Workshop to Develop Competency Objectives in Dental Public Health. Keynote address: Creating a future for dental public health. PMID- 2231529 TI - Competency objectives for dental public health. PMID- 2231530 TI - The John W. Knutson Distinguished Service Award in Dental Public Health--1989 recipient: John M. Frankel (posthumously). PMID- 2231532 TI - Co-culture of mouse embryos with oviduct and uterine cells prepared from mice at different days of pseudopregnancy. AB - Oviduct and uterine cell cultures were prepared from mice at different days of pseudopregnancy and their effects on the development of 1- and 8-cell mouse embryos in co-culture were examined. One-cell mouse embryos in co-culture with oviduct cells from 20 h to 120 h after hCG had a mean (+/- s.e.) cell number of 70.1 +/- 3.6, significantly (P less than 0.001) higher compared with those cultured in Whittingham's T6 medium supplemented with 5% fetal calf serum (T6 + 5% FCS) (30.4 +/- 1.6). Transfer of embryos, at 96 h after hCG, to synchronous pseudopregnant recipients showed that more embryos in oviduct co-culture formed fetuses than those cultured in T6 + 5% FCS. Co-culture of 1-cell embryos with uterine cells did not confer an advantage in cell numbers over T6 + 5% FCS. However, more 8-cell embryos formed blastocyst outgrowths after 100 h in co culture with uterine cells prepared from mice at Day 3 of pseudopregnancy than with uterine cultures prepared from mice at Day 1 of pseudopregnancy or oviduct cells. In addition, there was further improvement when the Day 3 uterine co cultures were supplemented with 1 or 10 ng progesterone/ml. These results highlight the importance of the oviduct and uterine cells during the different stages of preimplantation embryo development. PMID- 2231531 TI - Luteal inadequacy during the early luteal phase of subfertile cows. AB - A study was made of early luteal function (up to Day 6) in cyclic and pregnant heifers and also in older, subfertile cows. There were no differences in vivo or in vitro between cyclic and pregnant heifers, indicating no luteotrophic effect of the embryo at this stage, but the increase in postovulatory peripheral progesterone concentrations was delayed (P less than 0.01) and occurred more slowly (P less than 0.001) in the subfertile cows than in the heifers. The corpora lutea of the subfertile cows were heavier (P less than 0.001) than those of the heifers on Day 6. Basal progesterone production by dispersed luteal cells was similar between heifers and subfertile cows, but there was a difference (P less than 0.001) in the pattern of response to exogenous LH and PGE-2. Cells from subfertile cows were less sensitive to the stimulatory effects of PGE-2 and although LH increased (P less than 0.001) progesterone production by all cells, this stimulation by a low dose of LH was inhibited by PGE-2 in luteal cells from subfertile cows. This effect did not occur in the luteal cells from heifers. These results indicate the possibility that luteal inadequacy, due to a diminished response to circulating luteotrophic hormones, may contribute to embryo mortality in subfertile cows. PMID- 2231533 TI - Prostaglandin E-2 as a potential luteotrophic agent during early pregnancy in cattle. AB - Heifers slaughtered on Day 18/19 of pregnancy had significantly higher (P less than 0.001) concentrations of PGE-2 (measured as its methyl oxime) in uterine flushings than did animals slaughtered on Days 6 or 12 of pregnancy, or on Days 6 or 12 of the oestrous cycle. In addition, concentrations were higher in the uterine horn ipsilateral to the corpus lueum on Days 12 (P less than 0.05) and 18/19 (P less than 0.01) than in the contralateral horn. Incubation of dispersed luteal cells for 3 h with LH (0.1 or 100 ng/ml) and/or PGE-2 (0.01-1000 ng/ml) in vitro showed no differences in basal progesterone production or in the responses to exogenous hormones between pregnant and non-pregnant cattle. However, low doses of PGE-2 (0.01-10 ng/ml) inhibited the stimulation of progesterone secretion by the lower dose of LH. These findings indicate that although PGE-2 can stimulate progesterone synthesis by luteal cells it may also have inhibitory effects, and therefore its role in pregnancy requires further definition. PMID- 2231534 TI - Effect of season on seminal traits and serum hormone concentrations in captive male Siberian tigers (Panthera tigris). AB - Electroejaculates and serum samples were collected throughout the year from 5 male Siberian tigers. Semen quality, seminal plasma chemistry and serum hormone concentrations were evaluated and analysed as a function of season. Semen volume, concentration, motility, viability and morphology were not influenced by season. The ability of spermatozoa to undergo capacitation and penetrate zona-free hamster eggs did not differ due to season. Season had no influence on seminal plasma concentrations of acid phosphatase, calcium, glucose, potassium and phosphorus. Serum values of thyroxine and triiodothyronine were lowest (P = 0.002 and P = 0.03, respectively) during the summer months while cortisol showed no seasonal variation. Serum testosterone concentrations were higher in fall and early winter (P less than 0.001) than at other times of the year but were not correlated with semen quality. These results demonstrate that season has no effect on the semen production and quality of captive male Siberian tigers. PMID- 2231535 TI - In-vivo microscopy of the rat endometrial subepithelial capillary plexus during the oestrous cycle and after ovariectomy. AB - Blood flow through the endometrium was visualized by using incident-light fluorescence microscopy and a video image recorded for later detailed analysis. The subepithelial microvascular density was calculated for each day of the oestrous cycle and at 7 days after ovariectomy. The results showed that the microvasculature was significantly more dense at dioestrus I, pro-oestrus, and after ovariectomy than at oestrus, with dioestrus II being in between. Mean capillary path lengths running from arteriole to venule were longest at pro oestrus, followed by oestrus, dioestrus II, dioestrus I, and shortest after ovariectomy. The results suggest that endometrial growth and regression precede microvascular growth and regression. The technique of in-vivo microscopy provides an important new avenue for investigating the role of local factors in the control of the endometrial microcirculation. PMID- 2231536 TI - Effect of caffeine and of pentoxifylline on the motility and metabolism of human spermatozoa. AB - Human spermatozoa were washed and incubated with 6 mM-caffeine or 0.15-1.2 mM pentoxifylline. Sperm motility was measured by time-lapse photography, the rate of glycolysis by the release of tritiated water from 1 mM-[3-3H]D-glucose and the rate of mitochondrial respiration by the release of 14CO2 from 1 mM-[U-14C]-L lactate or 1 mM-[2-14C]pyruvate. Caffeine stimulated the majority of spermatozoa to convert from the 'rolling' to the 'yawing' mode of progression with a concomitant increase in lateral head displacement from 4.1 +/- 0.09 microns (343) to 6.7 +/- 0.25 microns (105) (mean +/- s.e.m. (number of spermatozoa)). There was a 45% decline in the percentage of progressively motile spermatozoa and a very small decrease in their velocity. Pentoxifylline had only a slight effect on lateral head displacement or percentage motility but produced a significant increase in velocity. Both compounds increased the rate of glycolysis by greater than 40% but elevated the rate of 14CO2 production to a smaller extent. The concentrations of ATP and ADP changed very little. We conclude that the glycolytic pathway in human spermatozoa can respond efficiently to changes in energy demand. PMID- 2231537 TI - Administration of pig relaxin to beef heifers 4 or 7 days pre partum. AB - Crossbred beef heifers (N = 36) were assigned to one of three treatment groups: untreated controls (C; N = 15); Group R4, treated with pig relaxin (1.0 mg i.m.) 4 days pre partum (N = 11); or Group R7, treated with pig relaxin (1.0 mg i.m.) 7 days pre partum (N = 10). Bioactivity of the pig relaxin (UMC-R-P8) was determined by the mouse interpubic ligament assay to be greater than or equal to 3000 U/mg, both before and after the experiment was conducted. Peripheral serum immunoreactive relaxin values were 7.5, 3.4, 2.5, and 1.5 ng/ml at 2, 4, 6 and 8 h after injection of relaxin, respectively. Gestation lengths were 282.9 +/- 1.1, 285.5 +/- 1.3 and 285.6 +/- 1.5 days for Groups C, R4 and R7 (C vs R4 + R7; P congruent to 0.08). Calving difficulty score (1 to 4) tended to be greater (P congruent to 0.08) for Group R4 and R7 heifers (C vs R4 + R7; 1.3 +/- 0.24 vs 1.75 +/- 0.28 + 2.04 +/- 0.32), but the incidences of dystocia and retained placentae were not influenced by treatment (P greater than or equal to 0.10). The mean concentration and concentration profile of daily serum progesterone, oestradiol-17 beta, dihydroprostaglandin F-2 alpha and relaxin were not affected by treatment from 6 days pre partum through 2 days post partum. Cervical diameter, cervical softness score, pelvic measurements, and vulva opening length during the periparturient period were not affected (P greater than or equal to 0.10) by treatment, but all of these characteristics changed over time (P less than or equal to 0.01), relative to calving. We conclude that i.m. administration of pig relaxin (greater than or equal to 3000 U) does not effectively alter periparturient characteristics of beef heifers. Discrepancies between these results and those reported for intracervical administration cannot be readily explained. PMID- 2231538 TI - Effect of immunization of ewes against prostaglandin F-2 alpha on the life-span of corpora lutea and oestrous behaviour during two breeding seasons. AB - Two adjuvants, Freund's complete adjuvant (FCA) and GNE (proprietary product; Intervet Ltd, The Netherlands), were used to immunize cyclic Finnish Landrace ewes (4-6/treatment) against a prostaglandin F-2 alpha-human serum albumin (PGF HSA) conjugate. Ewes were randomized to the following treatments: (a) control untreated, (b) control-5 mg HSA in FCA (control-HSA), (c) 5 mg PGF-HSA in FCA (FCA-5 mg), (d) 15 mg PGF-HSA in FCA (FCA-15 mg), (e) 5 mg PGF-HSA in GNE (GNE-5 mg) and (f) 15 mg PGF-HSA in GNE (GNE-15 mg). Ewes were monitored for oestrus (twice daily) and ovarian activity (progesterone concentrations in blood samples taken twice weekly) for 2 consecutive breeding seasons. In the first breeding season, the mean number of oestrous periods detected was 6.0, 5.7, 0.0, 0.2, 1.8 and 0.5 in control, control-HSA, FCA-5 mg, FCA-15 mg, GNE-5 mg and GNE-15 mg assigned ewes, respectively [pooled standard error of difference (s.e.d.) = 1.2]. A persistent CL formed, on average, 10.0, 10.0, 29.8 and 32.5 days after primary immunization (pooled s.e.d. = 14.6) in 6/6 FCA-5 mg, 6/6 FCA-15 mg, 5/6 GNE-5 mg and 4/4 GNE-15 mg-assigned ewes, respectively; these CL were maintained for, on average, 138.7, 139.0, 127.8 and 129.0 days, respectively (pooled s.e.d. = 15.9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231539 TI - Numbers of steroidogenic luteal cells in Booroola Merino ewes. AB - In Exp. 1 ovulation rates, plasma concentrations of progesterone, mean individual and total CL weights were determined on Days 4, 10 and 12 after oestrus of Booroola Merino ++ ewes and FF ewes. Mean ovulation rates ranged from 1.5 to 1.8 in ++ ewes and from 5.3 to 6.2 in FF ewes (P less than 0.01). There were no differences in plasma concentrations of progesterone or total luteal weight between the two groups on any of the days studied. Individual CL were smaller (P less than 0.01) in FF ewes than in ++ ewes. In Exp. 2 the numbers of luteal cells in CL collected from 5 ++ and 5 FF ewes on Day 10 of the oestrous cycle were morphometrically determined. The CL from FF ewes were smaller (P less than 0.01) and had fewer total steroidogenic cells (P less than 0.01), fibroblasts (P less than 0.01), and capillary endothelial cells and pericytes (P less than 0.05). However, the luteal cell volume density, number of cells/g tissue, average cell diameter or average cell volume was not different between the two groups of ewes for any cell type studied. It is concluded that the 5-6 CL in FF ewes function in an identical fashion to the 1-2 CL in ++ ewes. PMID- 2231540 TI - Microencapsulation of single, multiple, and zona pellucida-free mouse preimplantation embryos in sodium alginate and their development in vitro. AB - Preimplantation embryos obtained from immature superovulated B6D2F1 female mice were microencapsulated in sodium alginate singly, in multiples of 2 or 3, or denuded of their zona pellucida. Encapsulated embryos developed in vitro at a rate similar to control embryos. Development of zona pellucida-free embryos was significantly less than that of intact embryos, but there was no difference between encapsulated and non-encapsulated zona pellucida-free embryos. Development of 2- and 4-cell embryos in sodium alginate was independent of cell stage. This report demonstrates the usefulness of a viable, biodegradable embedding material for the microencapsulation of manipulated preimplantation mammalian embryos. PMID- 2231541 TI - Tissue spaces during development and regression of the decidual cell reaction in ovariectomized, steroid-treated mice. AB - Changes in the extracellular and blood spaces of the uterus were assessed from the distribution volumes of 51Cr-EDTA and 51Cr-labelled red blood cells during the development and regression of the artificially induced decidual cell reaction in ovariectomized, steroid-treated mice. The normally high values for uterine extracellular space (0.35-0.40 microliter/mg) fell to less than 0.20 microliter/mg in association with decidual growth. Uterine blood space increased from around 0.02 microliter/mg to 0.03-0.05 microliter/mg with decidual development. Induction of decidual regression by removal of s.c. progesterone implants caused a rapid decline in tissue blood volume to reach control values (0.01-0.02 microliter/mg) within 24 h and preceded any reduction in uterine weight. Uterine vascular permeability, as determined from the tissue accumulation of 125I-labelled human serum albumin, fell with a similar time course. Tissue extracellular space returned to the higher control values within 48 h of initiating decidual regression. PMID- 2231542 TI - Immunization against recombinant bovine inhibin alpha subunit causes increased ovulation rates in gilts. AB - Immunization of gilts in a commercial piggery against a fusion protein of the alpha subunit of bovine inhibin, produced by recombinant DNA methods, resulted in mean ovulation rate increases of 35% at the oestrus at which, under the piggery's management practices, they would have been mated. Sera from two immunized groups showed mean binding of 6.6% and 4.9% when assayed, at 1:800 final dilution, against iodinated bovine inhibin (Mr 31,000). Ovulation rates of immunized gilts were highly correlated with the ability of serum to bind iodinated native inhibin (r = 0.62; P less than 0.001), particularly when weight and age were included in the correlation (r = 0.72; P = 0.001), and inhibin binding accounted for 38% of the total variation in ovulation rate. Immunization caused no deleterious effects on growth rate or onset of oestrus. These results demonstrate the potential for use of such immunization to increase prolificacy in gilts and young sows. PMID- 2231543 TI - Opioid modulation of LH secretion by pig pituitary cells in vitro. AB - The effects of naloxone and beta-endorphin on LH secretion by pig pituitary cells were studied in primary cultures. On Day 4 of culture, cells (10(5) seeded/well) were challenged with 10(-9), 10(-8) or 10(-7) M gonadotrophin-releasing hormone (GnRH), 10(-10), 10(-9), 10(-8) or 10(-7) M-beta-endorphin or 10(-6) M-naloxone individually or in combinations. Secreted LH was measured at 4 h and 24 h after treatment and cellular content of LH was measured after 24 h. Basal LH secretion (control) was 23.5 +/- 7.6 and 36.9 +/- 10.3 ng/well at 4 h and 24 h, respectively. Relative to control at 4 h, 10(-9), 10(-8) or 10(-7) M-GnRH stimulated (P less than 0.05) LH secretion 140%, 210% and 250%, respectively. At 24 h, LH secretion was increased (P less than 0.05) by GnRH compared to control, but the dose-response to GnRH was absent. Naloxone increased (P less than 0.01) LH secretion 166 +/- 13% at 4 h and 141 +/- 13% (P less than 0.06) at 24 h. Secretion of LH after simultaneous addition of 10(-8) M-GnRH plus naloxone was greater (P less than 0.01) than after GnRH alone at 4 h but not at 24 h. beta Endorphin at 10(-10), 10(-9), 10(-8) or 10(-7) M failed to alter basal LH secretion at 4 h but decreased secretion at 24 h, while cellular LH content was similar to control at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231544 TI - Interrelationships between progesterone, 13,14-dihydro-15-keto PGF-2 alpha (PGFM) and LH in cyclic and early pregnant cows. AB - Plasma progesterone and LH secretion patterns were examined in 18 mature dairy cows during the oestrous cycle and after insemination. Blood samples were collected every 15 min for 8 h per day on Days 3, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 18, 19, 20 and 21 of the oestrous cycle, then, in the same cows, at the same times during early pregnancy. PGF-2 alpha secretion rates (as determined by plasma PGFM concentrations) were also monitored on Days 14, 16 and the day of, or equivalent to, luteal regression. Mean daily plasma progesterone concentrations were similar until Day 16 in cyclic and pregnant cows, after which values in non pregnant animals declined. Regression analysis indicated that progesterone concentrations were best described by a quadratic expression with fitted maximum values on Day 13 in non-pregnant animals but values increased linearly over the whole period to Day 21 in pregnant cows. The frequency, amplitude and area under the curve of LH episodes showed no significant differences between cyclic and pregnant animals. In pregnant cows, the amplitude and area under the curve of progesterone episodes increased linearly between Days 8 and 21, although no such increase occurred in cyclic cows. Low-level PGFM episodes were present in cyclic and pregnant cows on Days 14 and 16 after oestrus, and high amplitude episodes occurred in non-pregnant cows during luteal regression. Pregnant cows showed a significant depression of the amplitude, but not the frequency of episodes at the expected time of luteal regression. These results confirm that the corpus luteum of pregnancy secretes an increasing amount of progesterone per se and per unit of LH until at least Day 21 after mating. They further suggest that the corpus luteum of the cyclic cow may experience small episodes of PGF-2 alpha and be subjected to initial degenerative changes by Day 14 after oestrus, some time before the onset of definitive luteolysis. PMID- 2231545 TI - Expression of major histocompatibility complex antigens on the bovine placenta. AB - Immunohistochemistry was utilized to determine expression of the major histocompatibility complex (MHC) antigens on Day 8-9 hatched blastocysts and fetal membranes of mid- to late gestation cows and to examine the pattern of leucocytic infiltration into the gravid uterus. Hatched blastocysts were weakly positive for MHC class I antigens. In the mature placenta, chorioallantoic membranes in the interplacentomal area showed positive immunostaining for class I antigens on the chorionic epithelium but had no staining for class II antigens. There was an accumulation of lymphoid cells expressing class II antigens directly beneath the luminal epithelium of the endometrium. In addition, cells staining for leucocyte common antigen were present both within and beneath the luminal epithelium. Some cells positive for class II and leucocyte common antigen (CD45) were also associated with uterine glands. In the placentomes, class I antigens were expressed only on maternal caruncular septa. Fetal cotyledonary villi had no detectable immunostaining for class I and II antigens. No distinct pattern of leucocyte infiltration in the maternal caruncular tissue was observed; the caruncular septa contained some cells that were labelled for CD45 and a few class II-positive cells around blood vessels. The results indicate that the fetal placenta of the cow expresses MHC class I antigens in a regionally defined manner and there is a differential accumulation of lymphoid cells in the uterus. PMID- 2231546 TI - Prostaglandin F-2 alpha causes regression of an hCG-induced corpus luteum before day 5 of its lifespan in cattle. AB - The experimental objective was to evaluate how a spontaneously formed corpus luteum (CL) differed in its response to prostaglandin (PG) F-2 alpha, given during the first 5 days after ovulation, from a CL induced during dioestrus with hCG. Sixteen Holstein heifers were used during each of 2 consecutive oestrous cycles. During the first cycle (sham cycle), heifers were given no PGF-2 alpha (control) or PGF-2 alpha (25 mg, i.m.) on Day 2, 4 or 6 (oestrus = Day 0). During the second cycle (hCG-treated cycle), heifers were given hCG (5000 i.u., i.m.) on Day 10, followed by no PGF-2 alpha (control) or PGF-2 alpha on Day 12, 14 or 16, corresponding to 2, 4 or 6 days after the ovulatory dose of hCG. A new ovulation was induced in 13 of 16 heifers given hCG on Day 10. Luteolysis did not occur immediately in heifers given PGF-2 alpha on Day 2 or 4 during the sham cycle, but concentration of progesterone in serum during the remainder of the cycle was lower in heifers given PGF-2 alpha on Day 4 than in sham controls or heifers given PGF-2 alpha on Day 2 (P less than 0.05). Luteolysis occurred immediately in heifers given PGF-2 alpha on Day 6 of the sham cycle or on Day 12, 14 or 16 of the hCG-treated cycle, with concentration of progesterone in serum decreasing to less than 1 ng/ml within 2 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231547 TI - Purification, partial characterization, and development of a specific radioimmunoassay for goat placental lactogen. AB - Placental lactogen (PL) was isolated from goat cotyledonary tissue by a combination of mild alkaline extraction, anion and cation exchange chromatography, chromatofocussing and molecular filtration. The product, enriched 15,000-fold from the initial extract, was homogeneous when examined by SDS-gel electrophoresis (Mr 22,500) and isoelectricfocussing indicated a pI of 8.35 with a trace contaminant of pI 8.0. When assessed by relative binding activity in radioreceptor assays (RRA), goat PL exhibited somatotropic activity equivalent to 2.2 units/mg dry weight and lactogenic activity equivalent to 28.5 units/mg. A radioimmunoassay (RIA) for goat PL is described that is highly sensitive (190 pg/tube) and has acceptable repeatability within and between assays (6 and 13%, respectively). The assay is not affected by goat pituitary extracts or partly purified goat growth hormone and prolactin. Despite the marked increase in sensitivity of the RIA over that previously available when goat PL was measured by RRA, the hormone was not detected in jugular plasma of goats before Day 44 of pregnancy; concentrations increased thereafter and highest levels were measured during the last third of pregnancy in animals bearing triplets. Measurements by RIA are in general agreement with those obtained earlier in several studies in which RRAs were used. The hormone was detected in amniotic fluid. Maternal concentrations of goat PL declined before parturition and were undetectable by 18 h post partum. PMID- 2231548 TI - Morphology and proportion of inner cell mass of bovine blastocysts fertilized in vitro and in vivo. AB - The morphology and proportion of inner cell mass (ICM) of bovine blastocysts cultured in vitro or in vivo in rabbit oviducts after in-vitro fertilization of in-vitro matured follicular oocytes were compared with those of blastocysts fertilized in vivo by a differential fluorochrome staining technique. The delineation of each ICM cell was improved by the transfer of embryos derived from in-vitro fertilization to a rabbit oviduct although the cell-cell contacts of ICM cells were not as tight as those from in-vivo fertilization. The proportions (15.8 and 14.9%) of ICM in blastocysts cultured in vitro at early and expanded stages were significantly lower than those cultured in rabbit oviducts after in vitro fertilization and fertilized in vivo. These results show that the transfer of bovine embryos derived from in-vitro fertilization to the rabbit oviduct increased the proliferation of ICM cells to the level of embryos fertilized in vivo although the cell-cell contact of ICM cell is not improved by the process. PMID- 2231549 TI - Increased ovulation rate in gilts after oral administration of epostane. AB - In Phase I of this study to enhance ovulation rate and hence litter size, gilts received 0 (sham control), 0.625, 1.25, 2.5 or 5.0 mg epostane/kg body weight on Days 10, 11 and 12 of the oestrous cycle (5 gilts/group). After epostane treatment, plasma progesterone concentrations were reduced (P less than 0.01) in a dose-related manner, % progesterone decline = 21.30 x square root of (dose) + 10.45, R2 = 0.70, but recovered to pretreatment levels by 24 h. In Phase II the effects of epostane on ovulation rate and litter size were tested at two study centres. At each centre 108 gilts were treated with the same doses of epostane as used in Phase I and the doses were given for 7 days (Days 15-21) or 12 days (Days 10-21) during the first oestrous cycle. Gilts were inseminated twice during the oestrus after treatment and were slaughtered 30 days later. Mean (+/- s.d.) ovulation rate was 16 +/- 2.7 (N = 8) and 21 +/- 4.0 (N = 61) for control and epostane-treated gilts in Centre A and 12 +/- 2.4 (N = 5) and 17 +/- 3.8 (N = 55) respectively in Centre B (P less than 0.01 for both) and was dose related (ovulation rate = 3.38 x square root of (dose) + 16.17, R2 = 0.31). The effects of 7- or 12-day epostane treatment on ovulation rate were not different (P greater than 0.05), indicating that effects of treatment after Day 14 of the oestrous cycle are most important to subsequent ovulation frequency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231550 TI - Changes in protein synthesis and phosphorylation patterns during bovine oocyte maturation in vitro. AB - Sequential protein synthesis and protein phosphorylation patterns were generated by radiolabelling bovine cumulus-oocyte complexes after various periods of culture with [35S]methionine and [32P]orthophosphate respectively. The radiolabelled oocytes were assessed for their nuclear status and used individually for gel electrophoresis. Marked changes in the protein synthesis patterns were observed exclusively after germinal vesicle breakdown (GVBD), whereas oocytes which remained in the germinal vesicle stage showed a consistent protein synthesis pattern. The changes were observed after 8 and 16 h or culture, shortly after GVBD and before first polar body extrusion. From 3 h of culture, dominant phosphoprotein bands with apparent molecular weights of 24,000 and two between 50,000 and 60,000 were observed. The latter bands displayed slight molecular weight changes, which were not closely time related. After GVBD, the phosphoprotein band with Mr 19,000 was no longer observed. This study demonstrates that specific changes in protein synthesis and protein phosphorylation are programmed during bovine oocyte maturation. PMID- 2231551 TI - Folliculogenesis during the transitional period and early ovulatory season in mares. AB - Individual follicles were monitored by ultrasonography in 15 mares during the transitional period preceding the first ovulation of the year and in 9 mares during the first interovulatory interval. During the transitional period, 7 mares developed 1-3 anovulatory follicular waves characterized by a dominant follicle (maximum diameter greater than or equal to 38 mm) that had growing, static, and regressing phases. The emergence of a subsequent wave (anovulatory or ovulatory) did not occur until the dominant follicle of the previous wave was in the static phase. After the emergence of the subsequent wave, the previous dominant follicle regressed. The mean (+/- s.d.) length of the interval between successive waves was 10.8 +/- 2.2 days. Before the emergence of waves (identified by a dominant follicle), follicular activity seemed erratic and follicles did not reach greater than 35 mm. During the interovulatory interval, 6 mares developed 2 waves (an anovulatory wave and a subsequent ovulatory wave) and 3 mares developed only 1 detected wave (the ovulatory wave). The ovulatory follicle at the end of the transitional period reached 20 mm earlier (Day - 15), grew slower (2.6 +/- 0.1 mm/day; mean +/- s.e.m.) but reached a larger diameter on Day - 1 (50.5 +/- 1.1 mm) than for the ovulatory follicle at the end of the interovulatory interval (Day - 10, 3.6 +/- 0.2 mm/day, 44.4 +/- 1.0 mm, respectively; P less than 0.05 for each end point). The interval from cessation of growth of the largest subordinate follicle to the occurrence of ovulation was longer (P less than 0.05) for end of the transitional period (9.5 +/- 0.7 days) than for the end of the interovulatory interval (6.8 +/- 0.6 days). Results demonstrated the occurrence of rhythmic follicular waves during some transitional periods and the occurrence of 2 waves during some of the first oestrous cycles of the year. PMID- 2231552 TI - Extra-ovarian production of mature viable mouse oocytes from frozen primary follicles. AB - Isolated primary mouse follicles can be frozen successfully and thawed in the presence of 1.5 m-DMSO. Similar proportions of freshly collected and frozen thawed primary follicles undergo folliculogenesis in the absence of other ovarian tissue. Some of the mature oocytes recovered from these follicles were fertilized in vitro and, after transfer to pseudopregnant recipients at the 2-cell stage, developed into live young. Cryopreservation and extra-ovarian development of immature follicles provide a unique opportunity to store large numbers of female gametes. PMID- 2231553 TI - Photoperiodic requirements for LH release in juvenile broiler and egg-laying strains of domestic chickens fed ad libitum or restricted diets. AB - Photoperiodic response curves for LH release were obtained for juvenile female domestic chickens at 8 weeks of age by measuring changes in plasma LH concentrations after increasing the daily photoperiod from 8 to 10.5, 12.75, 15.25, 17.75 or 20 h. The birds were bred either for meat production (broiler) or commercial egg-laying and were fed ad libitum or a restricted diet, similar to that used under commercial conditions. Ovarian and oviduct growth was stimulated by 2 weeks after transfer to 20 h light/day in the dwarf broiler strain, irrespective of the dietary treatment, but not in birds of the egg-laying strain. Baseline concentrations of plasma LH were higher in the egg-laying than in the dwarf broiler strain birds. A significant effect of dietary treatment was observed on the changes in concentration of plasma LH in the nonphotostimulated dwarf broiler, but not in the egg-laying bird. There was no significant interaction between dietary treatment and photoinduced LH release in birds of either strain. The shortest photoperiod needed to stimulate LH release (critical daylength) was less than 10.5 h in the dwarf broilers and between 10.5 and 12.75 h in the egg-laying birds. The shortest photoperiod needed to stimulate the maximum release of LH (saturation daylength) was between 10.5 and 12.75 h in the dwarf broiler strain. The saturation daylength in birds of the egg-laying strain was longer, being between 12.75 and 15.25 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231556 TI - Factors affecting the acrosome reaction in human spermatozoa. AB - Large pieces of human cumulus oophorus were exposed for 20-30 min to washed spermatozoa or to spermatozoa recovered after a swim-up procedure, and then fixed for electron microscopy. Spermatozoa of both populations penetrated deeply into the cumulus within that time, and none of 48 observed clearly had undergone an acrosome reaction (AR). As measured by fluorescence microscopy, an AR rate of 12% in spermatozoa obtained at 4 h following a swim-up increased to about 25% in samples incubated in culture dishes for approximately 20 h. However, this latter AR rate was no different in the presence or absence of a cumulus/oocyte complex, and was only moderately greater in 50% follicular fluid. Nor was it affected to any degree by the absence of calcium or by a low (26 degrees C) temperature, both of which are regulators of the physiological AR in other species. By contrast, a clear dose-related enhancement of the AR by the calcium ionophore A23187 was almost completely Ca2(+)-dependent. We conclude that the human cumulus oophorus does not rapidly induce an AR in spermatozoa capacitated in vitro and, unlike the situation in some other mammals, that washed human spermatozoa do not first require a period of capacitation in order to penetrate it. The results also point to the likelihood that ARs monitored in free-swimming human spermatozoa are for the most part spurious or artefactual, and they show that in-vitro AR rates in such populations do not parallel their fertilizing ability. PMID- 2231555 TI - Critical progesterone requirement for maintenance of pregnancy in ovariectomized rats. AB - The minimum progesterone concentration required to maintain the pregnancy was studied by varying doses of progesterone given subcutaneously to rats ovariectomized on Day 8 of pregnancy. Injecting 3 mg progesterone plus 200 ng oestradiol benzoate daily provided serum progesterone values between 25.4 +/- 7.0 and 35.2 +/- 6.2 ng/ml throughout Days 10-19 which were significantly lower than normal levels (P less than 0.05), but resulted in 93.6% of fetal survival on Day 19 which was not significantly different from 93.3% in the control group. Injecting 2 mg progesterone plus 200 ng oestradiol benzoate daily gave progesterone values between 13.2 +/- 4.6 and 19.0 +/- 6.2 ng/ml and could not maintain fetal viability to Day 19 (14.2%, P less than 0.05 compared with control group). Critical times to supplement progesterone in rats ovariectomized on Day 8 or Day 15 were studied by varying the time of progesterone implantation after ovariectomy. Progesterone implants were administered 8, 12 and 24 h after ovariectomy on Day 8 and 24, 36 and 48 h after ovariectomy on Day 15. On Day 8, progesterone replacement could be delayed to 8 h but not 12 h, while on Day 15, progesterone replacement could be delayed up to 36 h but not 48 h after ovariectomy without affecting fetal survival. PMID- 2231554 TI - Seasonal variations in prolactin, growth hormone and thyroid hormones and the prolactin surge at ovulation do not affect litter size of ewes during pregnancy in the oestrous or the anoestrous season. AB - Injection of bromocriptine from 5 days before until 5 days after mating clearly suppressed the periovulatory prolactin surge in ewes in the anoestrous and oestrous season but did not change the litter size significantly. Progesterone, GH, TSH or thyroid hormone concentrations were not influenced by the bromocriptine treatment. The progesterone concentrations were lower during the first weeks after mating in the anoestrous season compared to the oestrous season, while there was no difference between pregnant and non-pregnant ewes. During later gestation this seasonal difference was only observed in the non pregnant ewes. At the same time there was a clear difference between pregnancy and non-pregnancy in both seasons. The prolactin, GH and thyroid hormone values also varied significantly during gestation. Since these patterns are identical in pregnant and non-pregnant ewes, the fluctuations are due to environmental factors and not to pregnancy or altered progesterone concentrations. In the anoestrous season prolactin, GH, T4 and T3 levels were higher than in the breeding season, while rT3 showed the opposite pattern. The TSH concentration did not differ between the two seasons. These results suggest that seasonal variations in prolactin, GH and thyroid hormones or the periovulatory prolactin surge do not affect litter size of ewes during pregnancy in the oestrous or the anoestrous season. PMID- 2231557 TI - Maintenance of human epididymal epithelial cell function in monolayer culture. AB - Cells liberated by enzyme treatment of tubules dissected out of human epididymides obtained at castration for prostatic carcinoma were cultured for up to 42 days on permeable supports. Outgrowth and monolayer formation was unrelated to the age of the patient or his treatment with anti-androgens. The cells comprising the monolayer were cuboidal and shorter than those in situ but their ultrastructure was characteristic of epithelial cells. There was no evidence of smooth muscle cells or fibroblast overgrowth. The cells manifested fluid-phase and adsorptive endocytosis from both apical and baso-lateral aspects and released into the medium alkaline and acid phosphatases and N-acetylglucosaminidase. PMID- 2231559 TI - Hysterectomy. A critical review. AB - Hysterectomy is of interest to the practicing obstetrician-gynecologist not only from the medical and surgical points of view but also because of the societal interest that the procedure attracts. The operation was first described in the third century A.D. writings of Soranus and before the turn of this century carried a very high surgical morbidity and mortality rate. With the technologic advances made during this century in both medical and surgical specialties, the operation has become quite safe, with a mortality rate of approximately 12/10,000 procedures. However, although it is possible to objectively measure the improved quality and increased quantity of life when hysterectomy is done for cancer treatment or other life-threatening conditions, it is difficult to so measure those parameters when hysterectomy is done solely to improve the quality of life. Today the physician's medical judgment and patient's understanding of the procedure are no longer the only criteria that have to be considered before surgery. Input by third-party payers, hospital administrators, quality assurance programs, second opinion programs and standards of practice in the geographic region also play a role. Also, alternatives to hysterectomy are being evaluated; in many circumstances they are being utilized today when hysterectomy would have been the treatment of choice before this decade. PMID- 2231558 TI - Sertoli cell-secreted protein(s) stimulates DNA synthesis in purified rat Leydig cells in vitro. AB - We have examined the effects of Sertoli cell-secreted proteins (SCSP) on [3H]thymidine incorporation by purified preparations (greater than 96%) of rat Leydig cells to determine whether Sertoli cells influence DNA synthesis in these cells in vitro. Incubation of Leydig cells isolated from testes of rats of ages 16 to 90 days with SCSP (Mr greater than 10,000) induced significant dose-, time- and age-related increases in [3H]thymidine incorporation by the cells. A dose response curve to SCSP showed that as little as 0.2 micrograms SCSP/ml consistently induced a small but significant increase (31% and 10% above control; P less than 0.001) in [3H]thymidine incorporation by Leydig cells isolated from immature (26 days) and mature (70 days) rats, respectively. The maximum response (230% and 48% above control) was obtained with a concentration of 18 micrograms SCSP/ml in cells isolated from immature and mature rats, respectively. Hydroxyurea, a specific inhibitor of replicative DNA synthesis, significantly (P less than 0.001) inhibited both basal and SCSP-induced [3H]thymidine incorporation in Leydig cells from immature and adult rats without affecting the viability of the cells. Incubation of immature rat Leydig cells in SCSP for 48 h also stimulated a 3-fold increase in cell number. The component of the crude SCSP which stimulated Leydig cell [3H]thymidine incorporation is trypsin-sensitive, heat-stable, and adsorbs to a heparin-agarose affinity column but not to concanavalin A-Sepharose. The secretion of this factor(s) by Sertoli cells is stimulated independently by FSH and testosterone. These results demonstrate for the first time that cultured Sertoli cells secrete a protein(s) which, in vitro, stimulates rat Leydig cell replicative DNA synthesis. PMID- 2231560 TI - Effect of interleukin-1 on gamete interaction and mouse embryo development. AB - Early stages of endometriosis have been shown to be associated with infertility. The pathophysiology of this relationship is unclear. To determine if interleukin 1 (IL-1), a peritoneal macrophage product, has any effect on gamete interaction and early embryo development, human recombinant IL-1 was added to the coincubation of gametes in the sperm penetration assay (SPA), human zona pellucida assay (ZPPA) and culture medium (Ham's F-10) used for processing semen samples with the layering method, with analysis of velocity and motility after 24 hours. IL-1 was also added to mouse embryos (two cells) cultured for 72 hours. The results showed that IL-1 caused impairment of SPA and ZPPA when compared to control medium, without significant alterations in sperm velocity and motility. Also, IL-1 demonstrated significant inhibition of mouse embryo development. These results help explain subfertility associated with early stages of endometriosis. PMID- 2231561 TI - Two urogenital sinus syndromes. Interstitial cystitis and focal vulvitis. AB - Forty-six young women had unusual and presumably noninfectious disorders of unknown etiology involving tissues derived from the embryonic urogenital sinus (urogenital sinus syndromes). Ten women had interstitial cystitis, and 25 had focal vulvitis. Eleven women had both interstitial cystitis and focal vulvitis. The affected groups were similar in demographic and other characteristics. Most were white and in their mid-20s. Both unusual conditions occurred in the same woman more often than could be expected by chance. This observation suggests that some common, perhaps autoimmune mechanism may be involved in the etiology of these syndromes. PMID- 2231562 TI - Stress incontinence and low urethral closure pressure. Correlation of preoperative urethral hypermobility with successful suburethral sling procedures. AB - Forty-eight women with genuine stress incontinence and low urethral closure pressure were treated with a suburethral sling procedure using polytetrafluoroethylene. All patients underwent a preoperative clinical evaluation and multichannel urodynamic testing. The clinical examination included a "Q-tip" test to determine the presence or absence of urethral hypermobility. Urethral hypermobility was defined as a maximal angle change of greater than or equal to 30 degrees from the horizontal, measured during straining or coughing in the lithotomy position. Thirty-four patients underwent repeat multichannel urodynamic testing three months postoperatively to determine the objective surgical success. Ninety-three percent of patients (27/29) with a positive preoperative Q-tip test were cured. Of patients with a negative preoperative Q tip test, only 20% (1/5) were cured. Preoperative urethral hypermobility was a good prognostic indicator of operative success when a suburethral sling procedure was used to treat genuine stress incontinence and low urethral closure pressure. PMID- 2231563 TI - Perinatal outcomes of twin pregnancies at term. AB - A review of a two-year experience in our community disclosed that 57% of twin pregnancies (118/207) deliver at term. Little attention has been focused on perinatal outcomes of twin pregnancies remaining undelivered after 36 completed weeks. Therefore, we reviewed our experience to determine whether our practice should change to maximize perinatal care. Nearly all the study pregnancies (115/117, or 97.5%) delivered by the estimated date of confinement. Fetal malpresentation, failure to progress and the patient's lack of desire for a vaginal birth after cesarean delivery were common reasons for the high cesarean rate (62/117, or 52%). The neonatal outcomes were favorable regardless of the route or interval between deliveries. Discordant fetal growth was found in only eight cases (6.8%). No perinatal deaths occurred, and five-minute Apgar scores less than 7 (2/234, or 0.9%) and rates of anomalies (5/234, or 2.1%) were not different from those in singleton pregnancies delivering during the same period. Using the principles of obstetric practice used in our community, we would expect the perinatal outcomes in term twin gestations to be favorable. PMID- 2231564 TI - Epidural analgesia. Effect on the likelihood of a successful trial of labor after cesarean section. AB - From October 1984 to April 1986, 237 women who had had an earlier cesarean section underwent a trial of labor (TOL). The delivery outcomes for 87 who received epidural analgesia were compared retrospectively with those for the 150 who did not. There were no overt uterine ruptures. The rates were similar for successful TOL, uterine scar dehiscence, blood transfusions, endometritis and one and five-minute Apgar scores. The rate of operative vaginal delivery was higher in the epidural group. When epidural subjects were divided into vaginal and cesarean delivery groups, the failed-TOL group differed from the successful-TOL group in greater maternal weight gain, heavier and longer infants, higher rate of oxytocin administration, less cervical dilation and higher station at epidural activation. When the oxytocin-treated subjects were excluded, however, the epidural and no-epidural patients had the same successful TOL rates (94% and 92%, respectively) and spontaneous vaginal delivery rates (70% and 76%, respectively). Epidural analgesia, when controlled for oxytocin use, appears to have no effect on the failed-TOL or operative vaginal delivery rate. PMID- 2231565 TI - Training obstetrics-and-gynecology residents to manage breast disease. Incorporation into a breast care clinic. AB - The American Board of Obstetricians and Gynecologists recently issued a directive that education in breast disease be incorporated into all residency training programs. At the University of Michigan Medical Center, the Comprehensive Breast Care Center (BCC) provides the vehicle for the education and training of residents in the area of breast disease. The department of obstetrics and gynecology is fully integrated and participates actively in the care of patients in the BCC. PMID- 2231567 TI - The nonstress test. Criteria for the duration of fetal heart rate acceleration. AB - Although the most common definition of a reactive nonstress test is an acceleration in the fetal heart rate of 15 beats per minute (bpm) for 15 seconds, some investigators require that the fetal heart rate acceleration be maintained at 15 bpm above the baseline for the entire 15 seconds (long criterion), and others require simply that the acceleration be 15 seconds from the beginning until the return to the baseline (short criterion). In 1,241 nonstress tests (NSTs) there was a statistically significant difference in the number of reactive tests between the short and long criteria (1,108 [89%] vs. 985 [79%], P less than .001). This difference in percentage of reactivity may be important when comparing studies performed by various investigators. In comparing cesarean section deliveries for fetal distress we were unable to find a difference in the ability to predict a poor outcome between use of the short and long criteria. However, a type II error is possible since the number of poor outcomes was small. We now use the short criterion for NST interpretation. PMID- 2231566 TI - Value of a screening fetal heart rate tracing in the latent phase of labor. AB - We studied the value of a screening fetal heart rate (FHR) tracing obtained on 405 women in the latent phase of labor on presentation to the labor-and-delivery suite. All pregnancies were at term and had a cephalic presentation. Thirty-two women in the sample studied underwent a cesarean section for fetal distress. Using that end point, a screening FHR tracing in the admitting room had a sensitivity of 57%, specificity of 98%, positive predictive value of 75% and overall efficiency of 95%. One- and five-minute Apgar scores and thick meconium staining of the amniotic fluid were also examined. While no statistically significant differences were found (P less than .2 for Apgar score and less than .06 for meconium), there was a trend that might have been significant if more women had been studied. A screening FHR tracing on all women at term in the latent phase of labor will identify the majority of those who will develop fetal distress in labor. Women with an abnormal screening tracing should be admitted to the hospital and the fetal status evaluated further. PMID- 2231568 TI - Occlusion of the vas deferens in dogs with a biocompatible hydrogel solution. AB - The surgically exposed vasa deferentia of 21 dogs were injected, under visual inspection, with Hypan N-90 acrylic hydrogel (50-150 microL). The hydrogel was deposited inside the vas lumen via a 22-gauge Teflon intercatheter. The solution gelled within 120 seconds. Semen was collected by manual collection and analyzed for volume, sperm count and viability. After occlusion with 150 microL of the polymer in the distal direction (direction of the testis), the volume of ejaculate (2.2 mL) did not change. Subsequent samples showed no viable or dead spermatozoa. The stained smears of the ejaculate showed the presence of cell debris, granulocytes and few epithelial cells. When the vas was injected with 50 microL of the polymer in either a distal or proximal direction, the occlusion effectiveness was 75% and 25%, respectively. In the proximal direction, granulomas were noticed in the vas wall where semen leaked through the injection port. Histology of successfully occluded vasa (with Hypan) showed no cellular reaction or fibrotic changes in the proximity of the polymer. For less than or equal to 20 weeks after vas occlusion, no evidence of abnormal morphology was found in the epididymal and testicular tissue. This highly biocompatible polymer solution, when gelled in contact with tissue fluid, offers safe and effective occlusion of the vas with the promise of reversibility. PMID- 2231569 TI - Amniography for confirming the diagnosis of monoamniotic twinning. A case report. AB - In a case of monoamniotic twinning, amniography was used to confirm the diagnosis. This modality, old but now employed infrequently, helps establish the absence of a dividing membrane and complements currently used ultrasound diagnostic methods. A successful outcome resulted. Amniography should be considered a useful diagnostic modality in the management of twin gestations and not be relegated to the past. PMID- 2231570 TI - Intrapartum, intranasal cocaine use and acute fetal distress. A case report. AB - Intrapartum, intranasal cocaine was used for relief of labor pains by a healthy woman with an uncomplicated pregnancy. Fetal hypoxemia and distress followed the event. A causal relationship between the intrapartum use of cocaine and the fetal distress was postulated. Cocaine abusers could benefit from hospitalization early in labor for close surveillance and monitoring, thus avoiding exposure to cocaine and its unpredictable systemic effects. PMID- 2231571 TI - Open section--open minds. PMID- 2231572 TI - Myalgic encephalomyelitis: an alternative theory. PMID- 2231573 TI - Wind of change-IV. Teaching hospitals in London 1938-1988. PMID- 2231574 TI - Measuring vitality. AB - Subjective perceptions of mental and physical energy were measured by the use of visual analogue scales (VAS) over the course of a week in a group of normal volunteers. These variables were found to correlate, highly both with one another and with assessments of vigour and fatigue measured with a standard adjectival format. In addition, high correlations were found with a measure of positive affect. These five variables also displayed characteristic patterns of diurnal variation. Physical and mental energy, vigour and positive affect were highest in the morning, falling progressively and significantly over the day. In contrast, fatigue showed the opposite pattern. Extraversion showed positive correlations with physical and mental energy, vigour and positive affect, and negative correlations with fatigue and negative affect, most being significant (P less than 0.05). Conversely, neuroticism showed a negative correlation with the first four energy variables but was positively related to fatigue and negative affect, most correlations again being significant. Physical and mental energy, vigour and positive affect also showed a positive correlation (P less than 0.01) with a measure of happiness. It is concluded that VAS-derived ratings of physical and mental energy are reliable indicators of self-perceived vigour and fatigue. They are easy to record and show sufficient short-term stability to be used in more extensive studies both of well-being and of its physiological correlates. PMID- 2231576 TI - Anorexia nervosa associated with acromegaloid features, onset of acrocyanosis and Raynaud's phenomenon and worsening of chilblains. AB - Patients with anorexia nervosa may develop many physical and endocrinological complications. We wish to report two patients who developed soft tissue swelling of their hands and worsening of their peripheral vascular disease, evidenced by the appearance of acrocyanosis and Raynaud's phenomenon and more severe perniosis, following the onset of their anorexia nervosa. PMID- 2231577 TI - Intolerance to oral and intravenous calcium supplements in atopic eczema. AB - Children treated with dietary restriction for food intolerance may require calcium supplementation, particularly if cows' milk and milk substitutes are not tolerated. We report two children with atopic eczema who reacted adversely to a number of calcium supplement formulations. PMID- 2231575 TI - Skin damage in chronic venous insufficiency: does an oxygen diffusion barrier really exist? AB - Eleven patients with lipodermatosclerosis (LDS) and 14 patients without venous or arterial disease underwent measurement of xenon-133 (133Xe) half-clearance times from the gaiter region of the leg. Xenon has similar diffusion characteristics to oxygen, and the investigation reflects the ability of the isotope to diffuse from the skin surface into capillary blood. Median skin half-clearance time for skin in the LDS group was 2.2 min and in the control group 2.1 min. From the subcutaneous tissues, the respective times were 14.1 and 17.4 minutes. These differences are not statistically significant. The study fails to yield evidence suggesting that an oxygen diffusion barrier exists in lipodermatosclerosis. PMID- 2231578 TI - Relationship between longevity and lifeline: a manual study of 100 patients. AB - The relationship between length of lifeline and age at death has been evaluated in 100 consecutive autopsies. A highly significant association between the two was discovered which was strengthened further when hand size was controlled for. We feel that a powerful new prognostic sign may thus be within grasp. PMID- 2231579 TI - Laboratory medicine--an American system: discussion paper. PMID- 2231580 TI - Styles of liaison psychiatry: discussion paper. PMID- 2231581 TI - Ovine toxoplasmosis: a review. PMID- 2231582 TI - Saint Vitus' dance: vital misconceptions by Sydenham and Bruegel. PMID- 2231583 TI - Heine's illness: the case for multiple sclerosis. PMID- 2231584 TI - Satire of medicine: the 18th century and beyond. PMID- 2231585 TI - Closed loop large bowel obstruction secondary to pancreatitis. PMID- 2231586 TI - Familial Raynaud's phenomenon and localized scleroderma associated with essential telangiectasia and cytogenetic abnormalities. PMID- 2231587 TI - Munchausen meningitis. PMID- 2231588 TI - Fatal cerebral oedema following trichloroethane abuse. PMID- 2231589 TI - Road traffic accidents and seatbelts. PMID- 2231590 TI - Cardiac arrhythmia and epilepsy. PMID- 2231592 TI - Mechanism and inhibition of cytochrome P-450 aromatase. PMID- 2231591 TI - Epistaxis induced by a non-steroidal anti-inflammatory drug. PMID- 2231593 TI - Benzotriazinones as "virtual ring" mimics of o-methoxybenzamides: novel and potent 5-HT3 receptor antagonists. PMID- 2231594 TI - Phosphorus-containing inhibitors of HMG-CoA reductase. 1. 4-[(2 arylethyl)hydroxyphosphinyl]-3-hydroxy-butanoic acids: a new class of cell selective inhibitors of cholesterol biosynthesis. PMID- 2231595 TI - Selective inhibition of urokinase by substituted phenylguanidines: quantitative structure-activity relationship analyses. PMID- 2231597 TI - Structural, conformational, and theoretical binding studies of antitumor antibiotic porfiromycin (N-methylmitomycin C), a covalent binder of DNA, by X ray, NMR, and molecular mechanics. AB - X-ray, NMR, and molecular mechanics studies on antitumor antibiotic porfiromycin (C16H20N4O5), a covalent binder of DNA, have been carried out to study the structure, conformation, and theoretical interactions with DNA. The crystal structure was solved by direct methods and refined to an R value of 0.052. The configurations at C(9), C(9a), C(1), and C(2) are S, R, S, and S, except for the orientation of the aziridine ring and (carbamoyloxy)methyl side chain. The five membered ring attached to the aziridine ring adopts an envelope conformation. The solution conformation is similar to that observed in the solid state except for the (carbamoyloxy)methyl side chain. Monovalent and cross-linked models of the drug bound to DNA have been energetically refined by using molecular mechanics. The results indicate that, in the case of monocovalent binding, the drug clearly prefers a d(CpG) sequence rather than a d(GpC) sequence. In the case of the cross linked model there is no clear-cut preference of d(CpG) over d(GpC), indicating that the binding preference of the drug may be kinetic rather than thermodynamic. PMID- 2231596 TI - Synthesis, biological profile, and quantitative structure-activity relationship of a series of novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. AB - A series of 9,9-bis(4-fluorophenyl)-3,5-dihydroxy-8-(alkyltetrazol-5-yl)- 6,8 nonadienoic acid derivatives 1 were synthesized and found to inhibit competitively the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The analogues having 1N-methyltetrazol-5-yl attached to the C8 position (3a, 4a, R1 = R2 = F) are the most active in suppressing cholesterol biosynthesis in both in vitro and in vivo models: the IC50 for the chiral form of 3a is 19 nM, Ki = 4.3 x 10(-9)M when Km for HMG-CoA is 28 x 10(-6) M;1 the ED50 (oral) value corresponding to the lactone derivative (4a, BMY 22089) is approximately 0.1 mg/kg. Further, BMY 21950 is nearly 2 orders of magnitude more active in parenchymal heptaocytes, from which most of the serum cholesterol originates, than in other cell preparations (such as spleen, testes, ileum, adrenal, and ocular lens epithelial cells; Table III). This apparent tissue specificity may be highly beneficial since the blocking of cholesterol biosynthesis in other vital organs could eventually lead to undesirable side effects. In addition to the chemical synthesis and biological evaluation, a theoretical study aimed at relating the HMG-CoA reductase inhibitory potency to the three-dimensional structure of the inhibitors was undertaken. With a combination of molecular mapping and 3D-QSAR techniques, it was possible to determine a logical candidate for the conformation of the bound inhibitor and to quantitatively relate inhibitory potency to the shape and size of both the binding site and the C8-substituent. PMID- 2231598 TI - DNA-directed alkylating agents. 2. Synthesis and biological activity of platinum complexes linked to 9-anilinoacridine. AB - Two different classes of cis-diaminedichloroplatinum(II) complexes linked to the DNA-intercalating chromophore 9-anilinoacridine have been synthesized and evaluated as DNA-targeted antitumor agents. Two different Pt chelating ligands were investigated (based on 1,2-ethanediamine and 1,3-propanediamine), designed to deliver the Pt in an orientation likely to respectively enhance either intrastrand or interstrand cross-linking. Although both sets of ligands were somewhat unstable under neutral or basic conditions with respect to disproportionation, the corresponding Pt complexes, once prepared, appeared to be quite stable. All the Pt complexes were monitored for purity by TLC, HPLC, and FAB mass spectra, and the mode of Pt coordination was established by 195Pt NMR spectroscopy. The complexes appeared to cause simultaneous platination and intercalative unwinding of plasmid DNA. In vitro studies were carried out with both wild-type and cisplatin-resistant P388 cell lines. Whereas cisplatin itself and the ethylenediamine and 1,3-propanediamine complexes used as standards were about 10-fold less active against the resistant line, the ethylenediamine-linked Pt complexes showed no differential toxicity between the two lines and the propanediamine-linked complexes showed significant differentials (up to 8-fold) in favor of the cisplatin-resistant line. However, these were no greater than those shown by the unplatinated ligands themselves. The majority of the acridine complexes were inactive in vivo against the wild-type P388 leukemia. They were very insoluble, and although a suitable formulation was found, this may have been a factor. It is also possible that these compounds bind in such a way as to direct the Pt away from the major groove. PMID- 2231600 TI - Synthesis, in vitro binding profile, and central nervous system penetrability of the highly potent 5-HT3 receptor antagonist [3H]-4-(2-methoxyphenyl)-2-[4(5) methyl-5(4)-imidazolylmethyl]thiazole. AB - 4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with this radioligand indicate that it effectively penetrates the blood-brain barrier upon peripheral administration. Thus, 5 should be a useful pharmacological tool for both in vitro and in vivo studies of this class of compounds. PMID- 2231599 TI - DNA-directed alkylating agents. 3. Structure-activity relationships for acridine linked aniline mustards: consequences of varying the length of the linker chain. AB - Four series of acridine-linked aniline mustards have been prepared and evaluated for in vitro cytotoxicity, in vivo antitumor activity, and DNA cross-linking ability. The anilines were attached to the DNA-intercalating acridine chromophores by link groups (-O-, -CH2-, -S-, and -SO2-) of widely varying electronic properties, providing four series of widely differing mustard reactivity where the alkyl chain linking the acridine and mustard moieties was varied from two to five carbons. Relationships were sought between chain length and biological properties. Within each series, increasing the chain length did not alter the reactivity of the alkylating moiety but did appear to position it differently on the DNA, since cross-linking ability (measured by agarose gel assay) altered with chain length, being maximal with the C4 analogue. The in vivo antitumor activities of the compounds depended to some extent on the reactivity of the mustard, with the least reactive SO2 compounds being inactive. However, DNA-targeting did appear to allow the use of less reactive mustards, since the S linked acridine mustards showed significant activity whereas the parent S-mustard did not. Within each active series, the most active compound was the C4 homologue, suggesting some relationship between activity and extent of DNA alkylation. PMID- 2231602 TI - Relaxant activity of 4-amido-3,4-dihydro-2H-1-benzopyran-3-ols and 4-amido-2H-1 benzopyrans on guinea pig isolated trachealis. AB - A series of 4-amido-3,4-dihydro-2H-1-benzopyran-3-ols and 4-amido-2H-1 benzopyrans related to the potassium channel activator cromakalim have been prepared and evaluated for their relaxant activity in guinea pig isolated tracheal spirals. Several analogues show enhanced relaxant activity relative to cromakalim in this preparation and the rank order of potency for those substituents investigated at C-6 was CF3 greater than CN greater than C2H5 greater than aza greater than or equal to CH3. One compound, trans-3,4-dihydro 2,2-dimethyl-4-(2-oxopiperidin-1-yl)-7-(trifluor omethyl)-2H- 1-benzopyran-3-ol (24), was resolved into its two enantiomers and the activity was shown to reside essentially in the (+)-isomer, adding further support to the suggestion that the smooth muscle receptor for these potassium channel activators is stereoselective. PMID- 2231601 TI - Variation in the aromatic ring of cromakalim: antihypertensive activity of pyranopyridines and 6-alkyl-2H-1-benzopyrans. AB - The synthesis and antihypertensive activity in the spontaneously hypertensive rat of two new series of analogues related to cromakalim (1) are described. In the first series, where the benzopyran nucleus has been replaced by a pyranopyridine nucleus, the position of the nitrogen atom has been found to be critical for activity, and the most potent compounds are the pyrano[3,2-c]pyridines. In the second series, where the powerful electron-withdrawing cyano group of compound 1 has been replaced by alkyl and phenyl groups, the order of antihypertensive potency is ethyl, isopropyl, tert-butyl greater than propyl, cyclopentyl greater than methyl greater than phenyl. PMID- 2231603 TI - Potential antimitotic agents. Synthesis of some ethyl benzopyrazin-7 ylcarbamates, ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates, and ethyl pyrido[3,4-e] as-triazin-7-ylcarbamates. AB - Ring analogues and derivatives of the 1,2-dihydropyrido[3,4-b]pyrazin-7 ylcarbamates (e.g., 29), antimitotic agents with antitumor activity, were prepared in the search for compounds with greater selectivity. Methods were developed for the conversion of substituted benzoic acids (1-4) to give benzopyrazines (12-16 and 21) and of substituted pyridin-2-carbamates (23, 38, and 41) to give 2-aminopyrido[3,4-b]pyrazin-7-ylcarbamates (32 and 36) and pyrido[3,4-e]-as-triazin-7-ylcarbamates (47 and 50). In vitro evaluation indicated that activity was reduced by removal of the pyridine ring nitrogen of 29 to give 14 and was destroyed by increasing the basicity of the pyrazine ring of 29 to give 32 and 47. PMID- 2231604 TI - Inhibition of enzymes of estrogen and androgen biosynthesis by esters of 4 pyridylacetic acid. AB - A variety of esters of 4-pyridylacetic acid have been prepared by base mediated exchange from the methyl ester. Several of the esters of alcohols that contained a cyclohexyl ring were potent inhibitors of human placental aromatase and of the rat testicular 17 alpha-hydroxylase/C17-20lyase complex. The most potent agents found against both enzyme complexes were the borneyl, isopinocampheyl, and 1 adamantyl esters. These were over 100 times more potent than aminoglutethimide against aromatase and of greater potency than ketoconazole against hydroxylase/lyase. Potency against either enzyme complex was reduced if the ester function was borne on the cyclohexyl ring in an axial rather than an equatorial position. Some differential selectivity could be introduced since whereas methyl substitution adjacent to the carbonyl group reduced the inhibition of aromatase, it increased that against hydroxylase/lyase. PMID- 2231605 TI - Inhibitors of the P450 enzymes aromatase and lyase. Crystallographic and molecular modeling studies suggest structural features of pyridylacetic acid derivatives responsible for differences in enzyme inhibitory activity. AB - Derivatives of 4-pyridylacetic acid are known to be inhibitors of the cytochrome P450 enzymes aromatase and lyase (17 alpha-hydroxylase/C17-20lyase), and are therefore of interest in the treatment of hormone dependent breast and prostate cancers. We report the determination of the crystal structure of one such derivative, the 4-tert-butyl cyclohexyl ester, and molecular modeling studies on two related inhibitors, the cyclohexyl ester and its alpha-methyl derivative. These latter two compounds show a marked difference in their relative activities against aromatase and lyase. Two models are proposed for the interaction of these molecules with the target enzymes on the basis of their ability to adopt conformations that partially mimic steroid substrates. From these models an explanation can be advanced for the fact that, compared with the unmethylated analogue, the (racemic) alpha-methylated compound is seven times poorer as an inhibitor of aromatase but seven times better as an inhibitor of lyase. The model proposed for binding to aromatase places the alpha-carbon of the ester group in the position occupied by C(2) of steroid substrates. In contrast, that proposed for binding to lyase places this atom in the position occupied by C(17) of steroid substrates. The introduction of steric bulk at C(2) is known to be unfavorable for aromatase inhibition, while its introduction at C(17) may lead to a better mimicry of the steroid D-ring and so improve lyase inhibition. PMID- 2231606 TI - Quinazoline antifolate thymidylate synthase inhibitors: alkyl, substituted alkyl, and aryl substituents in the C2 position. AB - Modification of the potent thymidylate synthase (TS) inhibitor N-[4-[N-[(2-amino 3,4-dihydro-4-oxo-6-quinazolinyl)methyl]-N-prop-2- ynylamino]benzoyl]-L-glutamic acid (1a) has led to the synthesis of quinazoline antifolates bearing alkyl, substituted alkyl, and aryl substituents at C2. In general the synthetic route involved the coupling of the appropriate diethyl N-[4-(alkylamino)benzoyl]-L glutamate with a C2-substituted 6-(bromo-methyl)-3,4-dihydro-4-oxoquinazoline followed by deprotection using mild alkali. Good enzyme inhibition and cytotoxicity were found with compounds containing small nonpolar groups in the C2 position with the 2-desamino-2-methyl analogue 3a being the most potent. Larger C2 substituents were tolerated by the enzyme, but cytotoxicity was reduced. Highly potent series were followed up by the synthesis of a number of analogues in which the N10 substituent was varied. In this manner a number of interesting TS inhibitors have been prepared. Although none of these was more potent than 1a against the isolated enzyme, over half of the compounds prepared were more potent as cytotoxic agents against L1210 cells in culture. The potential of such compounds as useful antitumor agents was further enhanced by the finding that the improved aqueous solubilities of compounds such as 3a over 1a were reflected in vivo in that 3a was at least 5 times less toxic to mice than 1a. PMID- 2231607 TI - Quinazoline antifolate thymidylate synthase inhibitors: 2'-fluoro-N10-propargyl 5,8-dideazafolic acid and derivatives with modifications in the C2 position. AB - The synthesis of 2'-fluoro-10-propargyl-5,8-dideazafolic acid and its 2-desamino, 2-desamino-2-hydroxymethyl, and 2-desamino-2-methoxy analogues is described. In general the synthetic route involved the coupling of diethyl N-[2-fluoro-4-(prop 2-ynylamino)benzoyl]-L-glutamate with the appropriate 6-(bromomethyl)quinazoline followed by deprotection with mild alkali. These four compounds together with the 2-desamino-2-methyl analogue were tested for their activity against L1210 thymidylate synthase (TS). They were also examined for their inhibition of the growth of the L1210 cell line and of two mutant L1210 cell lines, the L1210:R7A that overproduces dihydrofolate reductase (DHFR) and the L1210:1565 that has impaired uptake of reduced folates. Compared with their non-fluorinated parent compounds, the 2'-fluoro analogues were all approximately 2-fold more potent as TS inhibitors. Similarly, they also showed improved inhibition of L1210 cell growth (1.5-5-fold), and this activity was prevented by co-incubation with thymidine. All had retained or improved activity against both the L1210:R7A and L1210:1565 cell lines. PMID- 2231608 TI - Quinazoline antifolate thymidylate synthase inhibitors: benzoyl ring modifications in the C2-methyl series. AB - The synthesis of nine new 2-methyl-10-propargylquinazoline antifolates with substituents in the p-aminobenzoyl ring is described. In general the synthetic route involved the coupling of the appropriate ring-substituted diethyl N-[4 (prop-2-ynylamino)benzoyl]-L-glutamate with 6-(bromomethyl)-3,4-dihydro-2-methyl 4-oxoquinazoline followed by deprotection using mild alkali. The compounds were tested as inhibitors of partially purified L1210 thymidylate synthase (TS). They were also examined for their inhibition of the growth L1210 cells in culture. Compared to the parent compound 1a the 2'-fluoro analogue 2a exhibited enhanced potency in both systems whereas the 3'-fluoro analogue 3a showed enhanced growth inhibitory properties against L1210 cells despite being a poorer inhibitor of the isolated enzyme. Chloro, hydroxy, methoxy, and nitro substituents in the 2' position were also well tolerated by the enzyme but failed to give enhanced growth inhibition. The series was extended to cover analogues of the 2'-fluoro, 3'-fluoro, 2'-chloro, 2'-methyl, 2'-amino, 2'-methoxy, and 2'-nitro derivatives with modified alkyl substituents at N10. PMID- 2231610 TI - Synthesis and structure-activity relationships of new 9-N-alkyl derivatives of 9(S)-erythromycylamine. AB - A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride. Alternative syntheses employing hydrogenation methods have also been developed. These new 9-N-alkyl derivatives possess excellent antimicrobial activity in vitro and in vivo, especially when administered orally to treat experimental infections in mice. From structure activity studies, 9-N-(1-propyl)erythromycylamine (LY281389) was selected as the most efficacious derivative. These methods have also been extended to the synthesis of some 9-N,N-dialkyl derivatives of erythromycylamine. PMID- 2231609 TI - Design of potent and selective linear antagonists of vasopressor (V1-receptor) responses to vasopressin. AB - We report the solid-phase synthesis of 21 linear analogues of A and D, two nonselective antagonists of the vasopressor (V1) and antidiuretic (V2) responses to arginine vasopressin (AVP). A is Aaa-D-Tyr(Et)-Phe-Val-Asn-Abu-Pro-Arg-Arg-NH2 (where Aaa = adamantylacetyl at position 1). D is the des-Arg9 analogue of A. Nine new analogues of A (1-9) and 12 new analogues of D (10-21) were obtained. The following substitutions either alone or in combination were incorporated in A and/or in D: phenylacetic acid (Phaa) and tert-butylacetic acid (t-Baa) at position 1; D-Tyr2, D-Tyr(Me)2; Gln4; Arg6, Lys6, Orn6, MeAla7. The nine new analogues of A are (1) [Arg6], (2) [Lys6], (3) [Orn6], (4) [Phaa1,Lys6], (5) [Phaa1,Orn6], (6) [D-Tyr2], (7) [D-Tyr2,Arg6], (8) [Phaa1,D-Tyr2], (9) [Phaa1,D Tyr2,Arg6]. The 12 new analogues of D are (10) [Arg6], (11) [Lys6], (12) [Orn6], (13) [Phaa1,Lys6], (14) [Phaa1,Gln4,Lys6], (15) [Phaa,D-Tyr(Me)2,Lys6], (16) [Phaa,D-Tyr(Me)2,Gln4,Lys6], (17) [Phaa1,D-Tyr2,Gln4,Lys6], (18) [t-Baa1,Lys6], (19) [t-Baa1,Gln4,Lys6], (20) [Arg6,MeAla7], (21) [t-Baa1,Arg6,MeAla7]. All 21 peptides were examined for agonistic and antagonistic potencies in AVP V2 and V1 assays in rats. With the exception of 6, the eight remaining new analogues of A are equipotent or more potent than A as V1 antagonists. Peptides 2-9 are less potent than A as V2 antagonists. Three, 4, 5, and 9, exhibit significant gains in anti-V1/anti-V2 selectivities (selectivity ratio = 41, 14, and infinite, respectively), compared to A (anti-V1, pA2 = 7.75 +/- 0.07; selectivity ratio = 0.44). Peptide 9 is unique in both series. It is a highly potent V1 antagonist (anti-V1 pA2 = 8.62 +/- 0.11 and is the first linear peptide to exhibit substantial antidiuretic agonism (4.1 +/- 0.2 units/mg). With the exception of 12, the remaining 11 analogues of D are 8-40 times more potent than D as V1 antagonists. Eight of these peptides exhibit significant gains in anti-V1/anti-V2 selectivities compared to D (anti-V1 pA2 = 7.43 +/- 0.06; selectivity ratio = 1.6).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231611 TI - Synthesis and antiarrhythmic activity of 5,11-dihydro[1]benzoxepino[3,4 b]pyridines. AB - During further modification of the new antiulcer agent 5 (KW-5805), a 5,11 dihydro[1]benzoxepino[3,4-b]pyridine derivative, we found that some new derivatives had antiarrhythmic activity. So we continued synthesis and evaluation of a series of 5-substituted 5,11-dihydro[1]benzoxepino[3,4-b]pyridines for antiarrhythmic activity in chloroform-induced ventricular arrhythmias in mice and in ouabain-induced ventricular arrhythmias in dogs. In chloroform-induced ventricular arrhythmias, the 7-methoxy group played an important role in activity and the type of terminal side chain at position 5 had not obvious effect on potency. On the other hand, in ouabain-induced ventricular arrhythmias, the structure-activity relationship was highly specific and only four compounds, 9, 30, 34, and 35, were effective. Compound 9,5-[[2-(diethylamino)ethyl]amino]-7 methoxy-5,11-dihydro[1] benzoxepino[3,4-b]pyridine 1.5-fumarate, which exhibited low affinity for muscarinic acetylcholine receptors and a high ED100(mydriasis)/ED50(antiarrhythmic activity) ratio, was selected for further development and clinical evaluation as KW-3407. The synthesis and antiarrhythmic activity of optically active 9 is described. The order of potency of antiarrhythmic activity in ouabain-induced ventricular arrhythmias in dogs was ( )-9, (+/-)-9, and (+)-9. PMID- 2231612 TI - Evolutionary relationships among California serogroup viruses (Bunyaviridae) and Aedes mosquitoes (Diptera: Culicidae) AB - More than 100 published and four unpublished papers recording virus isolations of California (CAL) serogroup viruses from mosquitoes and other arthropods were analyzed, followed by a comparison of a contemporary classification of mosquitoes of the genus Aedes with a contemporary classification of CAL serogroup viruses. Using criteria of five or more total isolations of a given virus from a given species of mosquito, and a minimum infection rate of 1:10,000 or greater (more frequent), Aedes, and to a lesser extent Culiseta, species were found to be the arthropods most frequently involved as vectors. Such a comparison could not explain all virus-vector associations on the basis of coevolution of viruses in Aedes mosquito species, probably because of the crossing over of viruses to other mosquito species through horizontal transmission and because of deficiencies in currently available classifications. Coevolution of host-parasite systems is discussed, as are the inadequacies of contemporary taxonomic treatments of viruses and Aedes mosquitoes. The paper ends with hypothetical reconstructions of virus-mosquito relationships over time and possible routes of dispersal of California serogroup viruses to their present geographical distributions. PMID- 2231613 TI - Comparative efficiency of flagging and carbon dioxide-baited sticky traps for collecting the lone star tick, Amblyomma americanum (Acarina: Ixodidae). AB - Collections of Amblyomma americanum (L.) from five habitat types showed that significantly more ticks of all life stages could be collected by CO2-baited sticky traps than by the standard flagging technique. The effect of habitat type and season significantly influenced the number of ticks collected by both techniques. Traps baited with carbon dioxide revealed adult tick activity in several habitats several weeks earlier than did flagging, because flagging failed to efficiently recover ticks unless they had ascended vegetation. The CO2-baited traps required less time and effort and showed less variation for tick population surveys when compared with flagging. PMID- 2231614 TI - Survival and development of the immature stages of Culex annulirostris (Diptera: Culicidae) at the Ross River Dam in tropical eastern Australia. AB - Immature stages of Culex annulirostris Skuse from Ross River Dam were reared in the laboratory at constant temperatures (18.0, 24.5, 28.5 and 35.0 degrees C) and in the field in the presence or absence of predators. In the laboratory, survival from first instar to adult emergence increased from 5.5% at 18 degrees C to 96.5% at 35 degrees C. In the field predators increased mortality by almost 60%. Adult wing length increased inversely with constant temperature except at 18 degrees C. In the field the largest adults were produced in the presence of predators. The developmental threshold temperature (to) and thermal constant (K) were estimated from laboratory data to be 13.7 degrees C and 129.3 DD, respectively. K determined in the laboratory did not differ significantly from that required in the field (132.8 and 153.5 DD above 13.7 degrees C in the presence and absence of predators). Numbers of immature Cx. annulirostris at four sites in the dam rose to a peak after four or five generations and then rapidly declined. Overall survival of immatures was very low but was significantly higher at the one site where Melaleucas also occurred. Age-specific survival was highest in the first instar. Estimated survival from hatching to eclosion ranged from 4/1,000 to 185/1,000. Mortality appeared to be density independent and was attributed mostly to predation. PMID- 2231615 TI - Culex species (Diptera: Culicidae) from central Argentina: identification by electrophoretic zymograms and genetic relationships. AB - Starch gel electrophoretic zymograms were used for the taxonomic separation of mosquitoes of the genus Culex, possible vectors of encephalitis in Argentina. Catalase, hexokinase, malic enzyme, isocitrate and malate dehydrogenases, and leucine aminopeptidase were species markers that allowed the clear identification of individual Culex apicinus Philippi, Cx. bidens Dyar, Cx. brethesi Dyar, Cx. declarator Dyar and Knab, Cx. dolosus Arribalzaga, Cx. maxi Dyar, Cx. quinquefasciatus Say, Cx. saltanensis Dyar, and Cx. tatoi Casal & Garcia. Intraspecific polymorphism was revealed but did not preclude species separation. On the basis of allele frequencies, an index of genetic distance between species was calculated. Genetic affinities determined by electrophoretic data agreed with taxonomic affinities ascertained by conventional systematics. Thus, electrophoretic zymograms proved to be a powerful tool for the study of the genus Culex in Argentina. PMID- 2231616 TI - Failure to transmit Ehrlichia canis (Rickettsiales: Ehrlichieae) with Otobius megnini (Acari: Argasidae). AB - An ear tick, Otobius megnini (Duges) recovered from a child who had serologic evidence of ehrlichiosis, was examined for Ehrlichia species microscopically and by inoculation into a susceptible dog; no evidence of infection was found in the tick. Experimental transmission of E. canis by laboratory-reared O. megnini was attempted; neither transstadial nor transovarial transmission occurred. PMID- 2231617 TI - Nocturnal oviposition behavior of blow flies (Diptera: Calliphoridae). AB - It is widely held that blow flies, in general, and Phaenicia sericata (Meigen), in particular, are not active at night and do not lay eggs during that time. P. sericata is thought to require sunlight and warmth for oviposition. Three common and forensically important flies--Calliphora vicina (Robineau-Desvoidy), P. sericata, and Phormia regina (Meigen)--oviposited during the dark hours of the night during the summers of 1988 and 1989. Nocturnal oviposition can alter the usual estimate of the postmortem interval in homicide cases by as much as 12 h. Cases are presented that serve to change our concept of P. sericata from an obligate heliophile to a facultative heliophile that has a willingness to enter dim or dark places to oviposit. PMID- 2231618 TI - Mosquito bionomics and the lack of arbovirus activity in the Chino area of San Bernardino County, California. AB - Mosquito bionomics, including temporal abundance, metabolic status, and blood feeding patterns, and arbovirus activity were studied at representative dairy and residential habitats in Chino, Calif., during 1987 and 1988. Host-seeking Culex tarsalis Coquillett and Cx. quinquefasciatus Say females were more abundant and appeared earlier each season at traps near dairy breeding sources than at traps in residential areas, whereas Cx. stigmatosoma Dyar, which also breeds in dairy effluent, was most abundant at residential traps. All three Culex species remained gonotrophically active throughout winter and did not appear to enter diapause. Dairy cows diverted the normally ornithophagic Cx. tarsalis and Cx. quinquefasciatus females from avian hosts in dairy, but not in residential, habitats. Cx. stigmatosoma fed almost exclusively on birds. The diversion of host seeking Cx. tarsalis females to bovine hosts and reduced abundance because of mosquito abatement may have combined to reduce the receptivity of the Chino area to St. Louis encephalitis virus. PMID- 2231619 TI - Intraspecific variation in the reproductive capacity of Anopheles stephensi (Diptera: Culicidae). AB - Intraspecific variation in the reproductive capacity of Anopheles stephensi Liston females was studied under constant laboratory conditions. Of 421 engorged females examined individually throughout their lifetimes, 260 laid a total of 479 egg batches with a maximum of nine ovipositions per female. The number of eggs per oviposition varied from 5 to 247 (average 96.8). The number of ovipositions per female were correlated positively with the average number of eggs per batch and exhibited a negative binomial distribution among females, indicating that a small portion of the population exhibited a particularly high fecundity. Among the ovipositing females, the total fecundity and fertility ranged, respectively, from 5 to 1,084 eggs and from 0 to 1,036 larvae per female. The estimated maximal number of female progeny produced by a female in her lifetime was 317, and the estimates of net reproductive rate (Ro) and capacity for increase (rc) were 25.7 and 0.17, respectively. The number of eggs in the first oviposition was predictive of the total fecundity of a female. The wide range of individual variation in the reproductive capacity of An. stephensi emphasized the requirement for a large sample size for reliable estimation. PMID- 2231620 TI - Comparative field evaluation of permethrin and deet-treated military uniforms for personal protection against ticks (Acari). AB - The effectiveness of permethrin-impregnated (PI) versus permethrin-sprayed (PS) military battle dress uniforms was evaluated in protecting soldiers from tick bite. At the same time, an extended-duration formulation of N,N-diethyl-m toluamide (deet), when applied to clothing only, was evaluated and compared with the permethrin-treated uniforms. Testing consisted of exposing subjects, clothed in either untreated or the variously treated uniforms, to field populations of ticks during a series of 30-min field trials over a period of 21 d during July and August 1988. Permethrin, applied as either a spray (0.5% [AI]), or as an impregnant (0.125% [AI]/cm2), was more effective than deet (33.25% [AI]) applied to clothing only in protecting individuals from tick bite. The mean numbers of ticks on deet-treated, PI, and PS uniforms were 60, 97, and 98% lower, respectively, than on untreated uniforms against all encountered life stages of Amblyomma americanum (L), Dermacentor variabilis (Say), and Ixodes dammini Spielman, Clifford, Piesman and Corwin. PMID- 2231621 TI - Fecundity, metabolism, and body size in Anopheles (Diptera: Culicidae), vectors of malaria. AB - In four Anopheles species, An. albimanus, An. gambiae, An. stephensi, and An. quadrimaculatus Say, total protein, lipid, and carbohydrate present at eclosion, after feeding on sucrose, and after extreme starvation were quantified to study the effect of teneral and maximal reserves on subsequent fecundity and to judge the extent of reserve mobilization and the minimal irreducible amounts required for survival. All parameters were regressed on body size, presented as the cubic value of wing length. Teneral reserves were isometric with body size, were considerably lower than previously reported for Aedes aegypti (L.) and were sexually dimorphic with respect to reserves and body size, all being slightly reduced in males. On the average, up to 70% of the teneral female lipids and up to 50% of their teneral protein could be mobilized during nutritive stress. Conversely, access to sucrose for a few days led to a pronounced glycogenesis (up to 509%) and lipogenesis (up to 450% of the teneral values), depending on the species. In absolute terms, lipogenesis prevailed over glycogenesis. On a caloric basis, up to 30% of the blood meal protein was utilized for synthesis of yolk protein and lipid, and another 15% was deposited as an extra-ovarian, maternal protein and lipid store, perhaps compensating for the limited teneral reserves. A complete nitrogen budget revealed that in a given class of body size, roughly 80% of the blood meal protein was catabolized and excreted through the three major pathways of uricotely, ureotely, and ammonotely. Quantification of the hematin in fecal samples allowed a stoichiometrical determination of the amount of blood ingested. Eco-physiological aspects of larval feeding, teneral reserves, blood meal utilization, and possible behavioral adaptations to these physiological constraints are discussed and compared with previous data on culicine mosquitoes, stressing the invalidity of generalizations among these taxa. PMID- 2231622 TI - Survey of microhymenoptera (Hymenoptera: Chalcidoidea) parasitizing filth flies (Diptera: Muscidae, Calliphoridae) breeding in refuse and poultry farms in peninsular Malaysia. AB - Nine species of parasitoids were found parasitizing the pupae of filth flies breeding in refuse dumps and poultry farms throughout peninsular Malaysia. Spalangia were most common, consisting of Spalangia endius Walker, S. cameroni Perkins, S. gemina Boucek, S. nigroaenea Curtis, and two undescribed species. Other parasitoids collected were Pachycrepoideus vindemmiae Rondani, Dirhinus himalayanus Westwood, and an unidentified Hymenoptera. The parasitized fly hosts included Musca domestica L., Chrysomya megacephala (F.), Fannia sp., and Ophyra sp. S. endius was the most common parasitoid attacking M. domestica and C. megacephala at refuse dumps and poultry farms D. himalayanus were found to parasitize only M. domestica pupae collected at poultry farms. PMID- 2231623 TI - Attempted transmission of Ehrlichia risticii (Rickettsiaceae) with Stomoxys calcitrans (Diptera: Muscidae). AB - Experimental transmission of Ehrlichia risticii, the causal agent of Potomac horse fever, was attempted with adult stable flies, Stomoxys calcitrans, (L.) using two feeding schedules. In schedule A, a set of 140 flies was allowed to feed once on an experimentally infected donor pony and once 24 h later on a recipient pony. A different set of flies was used each day for a 12-d period. In schedule B, 240 flies were allowed to feed once daily for 12 consecutive d on the donor pony followed by five consecutive daily feedings on the recipient pony. E. risticii was isolated from the blood of the experimentally infected pony during the entire fly-feeding schedule. The recipient pony did not develop clinical signs of Potomac horse fever and remained seronegative to E. risticii up to 60 d after the last stable fly feeding. Mice injected intraperitoneally with emulsions of schedule A and B stable flies were seronegative for E. risticii 30 d after inoculation, and ehrlichial organisms were not demonstrated in impression smears from the digestive tracts of the flies. The stable fly did not transmit E. risticii under these experimental conditions. PMID- 2231624 TI - Temperature-dependent development and survival rates of Culex quinquefasciatus and Aedes aegypti (Diptera: Culicidae). AB - Development, growth, and survival of Culex quinquefasciatus Say and Aedes aegypti (L.) were determined at six constant temperatures (15, 20, 25, 27, 30, 34 degrees C). The Sharpe & DeMichele four-parameter model with high-temperature inhibition described the temperature-dependent median developmental rates of both mosquito species. In both species, body size generally decreased as temperature increased. Head capsule widths in all instars in both species were significantly greater at 15 than at 30-34 degrees C. Except for the third instar of Ae. aegypti, the larval body lengths in both species were significantly greater at 15 than at 34 degrees C. All instars and pupae of both species and the adults in Cx. quinquefasciatus were significantly heavier at 15 than at 27-34 degrees C. In Cx. quinquefasciatus, survival from eclosion to adult emergence was highest in the range from 20 to 30 degrees C (85-90%) and dropped drastically at 15 (38%) and 34 degrees C (42%). In Ae. aegypti, survival to adult stage was high at 20 (92%) and 27 degrees C (90%) and lowest at 15 degrees C (3%). PMID- 2231625 TI - Cleavage of purified bovine complement component C3 in larval Hypoderma lineatum (Diptera: Oestridae) hypodermins. AB - Proteinases isolated from first instars of Hypoderma lineatum (Villers) were assayed for their ability to degrade purified bovine complement component C3. Cleavage products were analyzed by SDS-PAGE followed by immunoblotting. Crude extracts (raw insect homogenate) and purified hypodermin A and B were effective in degrading the alpha chain of C3 at a concentration of 1 microgram/ml. At 10 micrograms/ml, raw insect homogenate caused total degradation of both chains of the molecule, whereas 50 micrograms/ml of hypodermin A was required to obtain similar results. Hypodermin B did not appear to cleave the beta chain of C3. No degradation of the C3 molecule was observed in the absence of added hypodermins. Complement degradation associated with Hypoderma infestations may allow the parasite to escape host defense reactions. PMID- 2231626 TI - Method for in situ hybridization to polytene chromosomes from ovarian nurse cells of Anopheles gambiae (Diptera: Culicidae). AB - A procedure for in situ hybridization to polytene chromosomes from the ovarian nurse cells of Anopheles gambiae Giles has been developed. This procedure involves a modification of established methods for Drosophila larval salivary gland polytene chromosomes. Treatment of chromosome squashes with xylene followed by slow rehydration provides required resolution of chromosome banding patterns, possibly because fatty contaminants are removed from ovarian nurse cell preparations. Using this procedure, unique DNA sequences from a genomic library of An. gambiae have been mapped on adult mosquito polytene chromosomes. The ability to locate genetic markers on chromosomes will allow correlation of physical and genetic maps. Such maps will facilitate identification of genetic loci and expand our knowledge of the genomic organization of An. gambiae. PMID- 2231627 TI - Ovicidal and larvicidal modes of action of fenoxycarb against the cat flea (Siphonaptera: Pulicidae). AB - The mode of action of the insect growth regulator, fenoxycarb, on embryogenesis of cat flea eggs, Ctenocephalides felis (Bouche), was evaluated biologically and morphologically. Newly oviposited flea eggs were aged for 0, 3, 6, 12, 24, 48, or 72 h and exposed to fenoxycarb (1.1 micrograms/cm2) on filter paper disks for 0 (60 s), 2, 4, 8, 12, or 24 h at 23 +/- 1 degree C and 70 +/- 3% RH. Following exposure, samples of flea eggs were processed for microscopic examination and seeded onto carpet swatches containing flea-rearing medium in order to assess egg hatch, and larval, pupal, and adult development. Fenoxycarb exhibited embryocidal activity against eggs in early blastoderm formation, blastokinesis, and advanced larval development up to hatching. The ovicidal effect of fenoxycarb was not restricted to any specific developmental stage of embryogenesis, and no significant relationship was found between duration of exposure and lethal or inhibitory effects. Indeed, exposure for as little as 60 s produced a lethal inhibition of embryonic development. Conventional microscopy and ultrastructural observations of flea eggs exposed to fenoxycarb showed extensive cellular and tissue damage of the developing embryos, including membrane lysis, burst cells, pycnotic nuclei with coalesced and clumped heterochromatin, swollen and ruptured mitochondria, cellular autolysis, and collapse and discoloration of the eggshell. Fenoxycarb also exhibited larvicidal activity against newly emerged and 24-h-old flea larvae. The midguts of larvae exposed to fenoxybarb appeared disrupted and distorted with large gaps. These data document the ovicidal and larvicidal modes of action of fenoxycarb against the cat flea. PMID- 2231628 TI - Longevity and fecundity of Musca domestica (Diptera: Muscidae) as a function of temperature. AB - Longevity and fecundity of adult house flies were determined at constant temperatures of 20, 25, 30, and 35 degrees C. At the four temperatures, respectively, the median mortality rates (1/days to 50% mortality) for females were 0.023, 0.041, 0.060, and 0.099 and for males were 0.029, 0.047, 0.066, and 0.085. The numbers of days for 50% of the eggs to be deposited for each temperature were 34.5, 21.3, 10.2 and 7.1, respectively. The total numbers of eggs deposited per female for each temperature were 184, 729, 709, and 506, respectively. Models were developed for longevity and fecundity and their distributions as functions of temperature. PMID- 2231629 TI - Notes on Dermacentor ticks (II): Taxonomic status of D. dentipes Koch and D. ferrugineus Koch (Acari: Ixodidae). AB - The type specimens of Dermacentor dentipes Koch and D. ferrugineus Koch were studied. D. dentipes is a junior synonym of D. marginatus Sulzer, and D. ferrugineus is a junior synonym of D. reticulatus Koch. PMID- 2231630 TI - Attempted Ehrlichia risticii transmission with Dermacentor variabilis (Acari: Ixodidae). AB - Larval Dermacentor variabilis (Say) (n = 327) were fed on Balb/C mice inoculated with Ehrlichia risticii, the etiologic agent of equine monocytic ehrlichiosis (Potomac horse fever). All mice displayed clinical signs of E. risticii infection at the time of feeding. After molting, resulting nymphs (n = 74) were fed on susceptible mice. No clinical signs were observed, and the mice remained seronegative for 6 wk after feeding. PMID- 2231631 TI - Evaluation of membranes for feeding Culicoides variipennis (Diptera: Ceratopogonidae) with an improved artificial blood-feeding apparatus. AB - An artificial blood-feeding apparatus for Culicoides variipennis (Coquillett) was improved by developing a simpler design to heat and mix the blood meal and by increasing the surface area for insect feeding. The skin from a 1- to 3-d-old chick and a reinforced silicone membrane were the most satisfactory of nine membranes evaluated for C. variipennis, with 81 and 83% mean blood-feeding rates, respectively. The operational advantages of the reinforced silicone membrane for feeding C. variipennis included its composition of readily available synthetic materials, easy fabrication, faster preparation than the chick skin, and its suitability for repeated use in colony maintenance and virus infection studies. PMID- 2231632 TI - Professional ethics: on transmitting complaints to one's colleagues. PMID- 2231633 TI - The kidney trade: or, the customer is always wrong. AB - Much of the opinion scandalized by recent reports of kidneys being sold for transplant is significantly inconsistent. The sale of kidneys is not substantially different from practices espoused, and indeed endorsed, by many of those who condemn the former. Our moral concern, I suggest, needs to focus on the customer's actions rather than the seller's; and on the implications for larger questions of the considerations to which this gives rise. PMID- 2231634 TI - Against the magnanimous in medical ethics. AB - Supererogatory acts are considered by some to be part of medicine, whereas others accept supererogation to be a gratuitous virtue, to be extolled when present, but not to be demanded. The present paper sides with those contending that medicine is duty-bound to benefit patients and that supererogation/altruism must per definition remain outside and beyond any role-description of the profession. Medical ethics should be bound by rational ethics and steer away from separatist views which grant exclusive privileges but also create excessive demands, way beyond what physicians perform or are willing and able to offer. PMID- 2231635 TI - Resource allocation: a plea for a touch of realism. AB - The problem of resource allocation in health has stimulated much thought and research, in attempts to provide objective, rational methods by which necessary choices can be made. One such method was proposed in a paper in this journal. The authors argued for a utilitarian approach, which they claimed to demonstrate was acceptable to society at large. This paper argues that the evidence supporting such a claim was flawed; such a utilitarian approach is not socially acceptable, and is therefore not relevant. Rather more relevant directions for research are discussed, based on the assertion that a degree of realism is essential when considering the problems of resource allocation. PMID- 2231636 TI - Resource allocation: whose realism? PMID- 2231637 TI - A plea for a touch of idealism: reply to P Whitaker. PMID- 2231638 TI - Let the patients smoke: a defence of a patient privilege. AB - I examine two kinds of arguments in favour of imposing restrictions on smoking by hospitalised psychiatric patients. First, I look at patient-centered arguments in favour of restrictions. These arguments focus on the benefits that patients will receive if their smoking is stopped or curtailed. Second, I examine arguments that seek to justify restrictions by citing the costs that smokers impose on others. Neither kind of argument justifies any meaningful restrictions on the smoking of hospitalised psychiatric patients. PMID- 2231639 TI - Evaluating ethical sensitivity in medical students: using vignettes as an instrument. AB - As a preliminary step to beginning to assess the usefulness of clinical vignettes to measure ethical sensitivity in undergraduate medical students, five clinical vignettes with seven to nine ethical issues each were created. The ethical issues in the vignettes were discussed and outlined by an expert panel. One randomly selected vignette was presented to first, second and third year students at the University of Toronto as part of another examination. The students were asked to list the issues presented by the patient problem. Responses from 281 students were obtained. These students identified an average of 2.72 ethical issues per vignette. Each response was classified under the domains of autonomy, beneficence and justice. Comparisons were made between classes and between vignettes. There was considerable variation between classes and the responses to different vignettes seem to indicate that different vignettes measure the various domains in different ways. It does appear that the use of vignettes is one way to measure aspects of ethical sensitivity in medical students but more study is required to clarify exactly what is being measured. PMID- 2231640 TI - A national committee for the ethics of research. AB - A National Committee for the Ethics of Research could consider new questions arising from innovations in research or practice, deal with multi-centre trials, adjudicate when separate local committees give conflicting advice about similar projects, or oversee the work of district committees. The value of each of these functions is assessed and it is concluded that a national committee would be most valuable in providing detailed evaluations of difficult or controversial issues. Though it could offer useful advice about multi-centre trials, local committees would probably wish to continue to consider research involving patients within their health districts even though approval had been given by a central committee. A national committee could usefully oversee the working of a system of quality control throughout the country, but the detailed monitoring of district committees would be done more effectively at regional level. PMID- 2231641 TI - Ethical appraisal for multi-centre medical research. PMID- 2231642 TI - Ethical review of multi-centred trials. PMID- 2231643 TI - The global distribution of health care resources. AB - The international disparities in health and health-care provision comprise the gravest problem of medical ethics. The implications are explored of three theories of justice: an expanded version of Rawlsian contractarianism, Nozick's historical account, and a consequentialism which prioritizes the satisfaction of basic needs. The second too little satisfies medical needs to be cogent. The third is found to incorporate the strengths of the others, and to uphold fair rules and practices. Like the first, it also involves obligations transcending those to an agent's relations and fellow-citizens. These conclusions are applied to international health-care provision, which they would transform. PMID- 2231644 TI - Temperance. AB - The kind of temperance discussed is the virtue of moderation concerning the pleasures of eating and drinking. A person lacks this moderation if either his desire for such pleasures causes conflicts with his own standards of appropriate behaviour or the standards themselves attach too much importance to the pleasures concerned. Opinions vary about the proper status of these pleasures, but people surely value them too highly if they place them above their health or the moral duty not to cause unnecessary suffering. Temperance concerns medicine because of its connection with health, ethics because it involves not only the good life for the individual but also the welfare of other creatures. PMID- 2231645 TI - Criteria of death. PMID- 2231646 TI - Genes and epilepsy. PMID- 2231647 TI - Adult polycystic kidney disease: knowledge, experience, and attitudes to prenatal diagnosis. AB - One hundred and ninety subjects from 100 adult polycystic kidney disease (APKD) families on the North Western Regional Genetic Register were interviewed to determine the likely demand for prenatal diagnosis. A detailed questionnaire was used to assess understanding and experience of clinical, therapeutic, and genetic aspects of APKD. Major features of the disease (presence of renal cysts which can lead to renal failure) and forms of therapy (dialysis and transplantation) were known; knowledge of less common features was related to experience. The cohort had had genetic counselling and the majority knew the risk to their own offspring, although the mechanics of the mode of inheritance was often misunderstood. Uptake of presymptomatic ultrasound testing was high, and some implications of early diagnosis are noted. A minority changed their reproductive behaviour as a result of APKD, and although the majority felt a prenatal test should be available, only 23% at high risk of passing on the disease and contemplating children felt they would be interested, and so far only one request for prenatal diagnosis has been received. Thus, demand appears to be low and to be related to perception of the seriousness of APKD. PMID- 2231648 TI - Genetic and environmental factors in hypospadias. AB - A case control study of hypospadias was performed from 1979 to 1987 in Alsace, north-eastern France. A total of 176 out of 60 847 male infants had hypospadias giving a prevalence at birth of 2.89 per 1000 male newborns; 15.3% of all infants with hypospadias also had other malformations. Renal and urinary tract malformations were present in 37.0% of the infants with hypospadias and other additional malformations. None of the numerous aetiological factors which were studied was correlated with hypospadias except low weight of the placenta. The recurrence risk for brothers was 17.0% (an empirical risk of about 1 in 6) and the heritability coefficient was 56.9%. First degree relatives of infants with hypospadias had more malformations other than hypospadias than controls. These results have to be taken into consideration for genetic counselling. PMID- 2231649 TI - Repeated freezing and thawing of peripheral blood and DNA in suspension: effects on DNA yield and integrity. AB - The possibility of DNA degradation is of concern to all involved in the storage of DNA, whether for diagnostic or research purposes. Many DNA banks are at present maintained at low temperatures, but optimum conditions for storage and handling have yet to be fully assessed. Both DNA and fresh blood have been subjected to repeated cycles of freezing and thawing and DNA extracted from the blood. DNA yield has been established and integrity examined by digestion, electrophoresis, and Southern blot analysis using DNA fingerprinting techniques. No degradation of DNA could be detected using these techniques; however, DNA yield was shown to be adversely affected by freezing, with yield reduced by more than 25% in blood samples frozen only once. PMID- 2231650 TI - Sotos syndrome. PMID- 2231651 TI - Occurrence of the alpha thalassaemia-mental retardation syndrome (non-deletional type) in an Australian male. AB - The rare association of alpha thalassaemia and mental retardation has been described previously. Molecular studies of the alpha globin cluster in these cases have been heterogeneous, with some patients having large deletions while in others the alpha globin complex appears to be intact (non-deletional). The non deletional cases form a distinct group whose features include severe mental retardation, haematological changes of haemoglobin H (Hb H) disease, developmental defects, and unusual patterns of inheritance. To date, five cases have been described with non-deletional alpha thalassaemia-mental retardation. We present here a further example of a young male of Northern European origin who appears to have the non-deletional form of the disease. Clinical features included severe mental retardation, Hb H disease, and developmental defects similar to those reported previously. DNA mapping, including pulsed field electrophoresis, showed no evidence of deletions within the alpha globin cluster. Karyotypic analysis indicated an increase in random breakage, which has been observed previously in one case of deletional alpha thalassaemia-mental retardation. Profuse Hb H bodies and Hb H on electrophoresis were consistent with Hb H disease. However, the latter was present at a relatively low level (1.6%) and, as well, the mean corpuscular volume (82.8 fl) and mean corpuscular haemoglobin (26.4 pg) were surprisingly high. Our findings are compared to other cases described with the non-deletional Hb H-mental retardation syndrome. PMID- 2231652 TI - Chromosome imbalance, normal phenotype, and imprinting. AB - A duplication of the sub-bands 1q42.11 and 1q42.12 was found in a boy and his mother. The proband has short stature (around the 10th centile) but a normal phenotype and psychomotor development. His mother is also asymptomatic. We found 30 published cases of normal subjects with an imbalance of autosomal euchromatic material. In these cases the imbalance involved either only one G positive band or a G positive and a G negative band. Thus the absence of a phenotypic effect cannot always be ascribed to the deficiency in the G positive bands of coding DNA. Moreover, in some cases, the method of transmission of the chromosome abnormality was such that an imprinting effect could be postulated. PMID- 2231653 TI - Partial monosomy for chromosome 22 in a patient with del(22)(pter--- q13.1::q13.33----qter). AB - An 18 month old girl with partial monosomy for the long arm of chromosome 22 is described. The karyotype was 46,XX,del(22)(pter----q13.1::q13.33----qter). To our knowledge this is the first report of monosomy for this specific segment of chromosome 22. Clinical features include developmental delay in all areas, hypotonia, macrosomia, full cheeks, eyebrows, and eyelids, mild epicanthus, wide nasal bridge, long philtrum, and thick lower lip. Parental chromosome studies were normal. PMID- 2231654 TI - Alstrom's syndrome: further evidence of autosomal recessive inheritance and endocrinological dysfunction. AB - We report a case of Alstrom's syndrome with hypothyroidism in addition to the cardinal features of blindness, deafness, obesity, and insulin dependent diabetes mellitus. The parents were first cousins once removed which strengthens the case for autosomal recessive inheritance. PMID- 2231655 TI - Another case of microcephaly, facial clefting, and preaxial polydactyly. AB - We describe a nine month old boy with failure to thrive, developmental delay, bilateral cleft lip and palate, and left preaxial polydactyly. The features are similar to those in a child described by Howard and Young and may be the second case of a previously unknown syndrome. PMID- 2231657 TI - Deletion Xp22.3. PMID- 2231656 TI - Dominantly inherited cleft lip and palate. PMID- 2231658 TI - Medical genetics in Romania. PMID- 2231659 TI - Laser Doppler flowmetry. PMID- 2231660 TI - Laser Doppler flowmetry. PMID- 2231661 TI - A critical review of laser Doppler flowmetry. AB - Laser Doppler flowmetry (LDF) is now a well-established, non-invasive technique for measuring microvascular blood perfusion. However, there are a number of factors which can seriously affect the interpretation of the laser Doppler signal which are often not considered during routine use. These include: consideration of signal processing limitations, choice of processing bandwidth, problems with motion artefact and instrument calibration, the effect of probe pressure on the skin, and the type of laser used. This paper reviews many of the problems and limitations frequently encountered using the laser Doppler technique. PMID- 2231662 TI - Lower limb sympathectomy assessed by laser Doppler blood flow and transcutaneous oxygen measurements. AB - In a retrospective study of critical ischaemia of the lower limb, sympathectomy appeared to be of value in the majority of patients. We therefore assessed sympathectomy by measuring skin blood flow before and after the procedure using laser Doppler flowmetry (LDF) and transcutaneous oxygen tension (TCpO2) techniques. Twenty patients underwent chemical sympathectomy and there was one surgical procedure. Measurements were performed before and 1 week after sympathectomy below the knee and on the forefoot. Symptomatic improvement occurred in 20 of 21 patients. This study demonstrates that skin blood flow in the leg and foot is improved by sympathectomy and confirms objectively our clinical impression. PMID- 2231663 TI - The microvascular lesion in venous ulceration and the role of the white blood cell. AB - White blood cells have recently been implicated in the development of venous ulceration. Fifty subjects (14 normal controls, 21 with superficial venous insufficiency (SVI), and 15 with deep venous insufficiency (DVI] have been studied in the supine and dependent positions in a constant environment using video capillary microscopy, laser Doppler flowmetry and transcutaneous oxygen measurements to the gaiter skin. All three groups had an increase in visible capillary loops and a reduction in blood flux in the gaiter region when the leg was placed in the dependent position. There was a decrease in the leg/chest transcutaneous oxygen ratio in all three groups on dependency. These results suggest that the 'oedema protection reflex' (as measured by the laser Doppler probe) is present not only in normal and SVI limbs but also in DVI limbs. The increase in visible capillary loops suggests that intraluminal capillary occlusion is not occurring within the period of this study. The exact microvascular defecit of venous ulceration remains to be explained. PMID- 2231664 TI - Laser Doppler assessment of human colonic blood flow. AB - We have used laser Doppler flowmetry to assess human colonic blood flow in patients with healthy mucosa and in those with active proctitis. We report a significant correlation between colonic serosal laser Doppler flux readings and serosal tissue oxygen tension (n = 45: r = 0.671: p = 0.001). Mucosal blood flow was measured using the PF309 probe of a Perimed Pf2b set on 12 kHz frequency shift. There was no significant difference throughout the colon in healthy patients. The flow in rectal mucosa was significantly higher in patients with proctocolitis than in normal mucosa. PMID- 2231665 TI - Skin blood flow changes following intradermal bradykinin injections measured by laser Doppler flowmetry: comparison with weal and flare. AB - Intradermal injections of normal saline and different concentrations of bradykinin were made into the forearms of healthy volunteers. Cutaneous blood flow was recorded just outside and over the centre of the weals by laser Doppler flowmetry (LDF), and flare area and weal volume were measured. There were concentration-related changes in the mean LDF output adjacent to the weal, flare area and weal volume. LDF recordings performed over the centre of the weals, however, failed to show any dose-response relationship. When similar concentrations of bradykinin were injected intradermally and the skin response measured by the above parameters, there was less variation in the mean LDF output adjacent to the weal than flare or weal measurements. The non-invasive technique of LDF is a useful, objective and sensitive technique of quantifying the skin blood flow changes induced by intradermal bradykinin and provides an alternative method of quantifying skin response to intradermal bradykinin to measurement of flare or weal sizes. PMID- 2231666 TI - Assessment of the neurogenic flare response as a measure of nociceptor C fibre function. AB - A modified method for quantitative measurement of nociceptor C fibre function is described. The electrophoresis of acetylcholine stimulates C fibres to produce an axon reflex flare which is measured by laser Doppler flowmetry. The use of the dorsal, rather than the plantar, surface of the foot at a skin temperature of 32 33 degrees C rather than 34-35 degrees C improves the sensitivity of the technique. Acetylcholine produces an earlier and more predictable response than normal saline, which is approximately half maximal at a current of 0.2 mA and maximal at 1.0 mA. The use of different current strengths should allow more detailed assessment of neurogenic inflammation and the effects of drugs and disease states on C fibre function. PMID- 2231667 TI - Laser Doppler flowmetry and bone blood flow in an isolated perfused preparation. AB - A preparation of an isolated bovine forefoot was established which could be perfused with blood at variable rates. A laser Doppler flowmeter probe inserted into the cancellous bone of the metatarsal produced a signal which varied with changes in perfusion rate and oscillated in synchrony with the peristaltic perfusion pump. A stronger laser Doppler signal was obtained when the probe was inserted into a drill hole than when inserted into a hole bored with a guide wire. It appears that laser Doppler flowmetry has potential intraoperative use when the viability of bone is in question. PMID- 2231668 TI - Measurement of blood flow in the chick egg yolk sac membrane. AB - Blood vessels of the yolk sac membrane are the transport route by which a chick embryo obtains nutrients from the egg yolk. After 4 days of incubation at 37 degrees C a sparse network of blood vessels are visible within the membrane and they become denser over the following days. The preparation has been used to assess angiogenesis. Using visual inspection to assess the growth of new vessels towards pellets of test substances placed on the membrane surface, responses are judged negative or positive. Laser Doppler flowmetry has been used to investigate the potential of this technique to quantify blood flow through the yolk sac membrane. Measurements have been taken from capillary beds and single larger vessels over a range of temperatures and from avascular yolk and egg white using a Perimed PF3 with PF310 bent-tipped probe. Capillary beds exhibited vasomotion (about one cycle per minute) and oscillations of longer duration (about five cycles per hour). Cardiac pulses, strongly present in larger vessels (mean 90 pu, pulse 75 pu), were not easily identified in the capillary bed. Avascular yolk measurements gave flux values (due to Brownian motion of yolk proteins) which were greater than for capillary beds but without oscillations. Angiogenesis was stimulated by pellets containing 2 micrograms of basic fibroblast growth factor. There were significant increases in single vessel blood flow after 24 h compared with blank control pellets placed on the same egg. PMID- 2231669 TI - Electrophoretic type B2 of carboxylesterase B for characterisation of highly pathogenic Escherichia coli strains from extra-intestinal infections. AB - The frequency of electrophoretic types B1 (fast mobilities) and B2 (slow mobilities) of carboxylesterase B, and alpha-haemolysin and mannose-resistant haemagglutinin (MRHA) production were compared in 705 strains of Escherichia coli isolated from cases of septicaemia, urinary tract infection (UTI) and other extra intestinal infections from different geographical origins, in particular France, America (USA and Canada) and Oceania (Australia and New Zealand). In all groups of strains, whether classified according to their clinical or their geographical origin, electrophoretic type B2 was phenotypically linked with alpha-haemolysin and MRHA production. Haemolytic type B2 strains were isolated more frequently from France and Oceania than America whereas the proportions demonstrating production of MRHA were similar among the three groups. Type B2 strains were more frequently isolated from UTI and other infections than from septicaemia. This is attributed to the high frequency of immunocompromised subjects in the septicaemia group. Our results establish the suitability of using the type B2 of carboxylesterase B as a molecular marker for highly pathogenic E. coli strains implicated in extra-intestinal infections in man. PMID- 2231670 TI - Analysis of the porphyrin content of fluorescent pus by absorption spectrophotometry and high performance liquid chromatography. AB - Extracts of 19 samples of pus which showed red fluorescence with ultraviolet light were screened for the presence of porphyrins by absorption spectrophotometry. All those which showed spectra typical of metal-free porphyrins were analysed by high performance liquid chromatography to identify the porphyrins present. These were predominantly the di-carboxylic porphyrins, deuteroporphyrin and mesoporphyrin, and another which was thought to be pemptoporphyrin. This combination matched those reported previously in normal stools. Protoporphyrin IX was shown not to be the most common fluorescent pigment in pus and was never present alone. However, the di-carboxylic porphyrins may be produced by bacterial metabolism of its labile vinyl side-chains. Black-pigmented bacteroides (the melaninogenicus group of Bacteroides spp. and Porphyromonas spp.) were isolated from 12 (63%) of the 19 pus samples; these may produce protoporphyrin IX by the demetallation of haem. PMID- 2231671 TI - The relationship between colonisation, secretor status and in-vitro adhesion of Candida albicans to buccal epithelial cells from diabetics. AB - This study investigated whether oral candida infection in diabetics and adhesion of Candida albicans to buccal epithelial cells in vitro were related. Buccal cells from 50 patients with diabetes mellitus showed a significant increase in adhesion of C. albicans strain CDS 88 compared with those collected from 50 non diabetic controls matched for age, sex and denture status. Oral candida carriage, candida infection and secretor status were also investigated in both groups. The frequency of carriage was increased, but not significantly, and there was a significantly higher incidence of candida infection in diabetic patients compared with controls. Diabetic patients who were non-secretors had a significantly increased frequency of oral candida carriage. PMID- 2231672 TI - Characterisation of opacity factor from group-A streptococci. AB - Extracellular opacity factor (OF) from group-A Streptococcus M-type 22 was purified by ammonium sulphate precipitation followed by ion-exchange on DE-52 cellulose and gel filtration on sephacryl S-400. OF was eluted near the void volume and shown to be heterogenous by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Antiserum to ammonium sulphate-purified OF from a cell-free culture supernate was prepared in rabbits. All preparations of OF from supernate and cell-extract were inhibited by the antiserum. No M protein was detected in the OF samples from various purification steps. The purified OF showed activity at a broad pH range with optimal activity at pH 6; it was inactivated considerably at high temperatures. Enzyme activity was inhibited by pepstatin A, but was unaffected by serine proteinase inhibitor, aprotinin, ethylene diamine trichloroacetic acid, N-ethylmaleimide, iodoacetamide and mercaptoethanol. This suggests that OF is an aspartic proteinase. PMID- 2231673 TI - Ultrastructure of a spiral micro-organism from pig gastric mucosa ("Gastrospirillum suis"). AB - The ultrastructural features of a helical-shaped bacterium occurring in the stomach of pigs, within the mucus on the mucosal surface of antral pits, were examined. The bacterial cell had three to eight spiral turns, flattened and truncated ends and was approximately 4.0 microns long and 0.6 microns wide. In some sections, up to six flagella, about 22 nm in diameter, were seen arising from each pole. The cytoplasm contained sparse, irregular granules, numerous ribosomes and large single-layered membrane-bound granules. In the flagella insertion area, there was a highly electron-dense component, the "polar membrane". This micro-organism differed from similar bacteria described in cats, dogs and monkeys, and may cause inflammation in the antral mucosa of pigs similar to Helicobacter pylori infection in man. Furthermore, it was morphologically similar to the spiral micro-organism distinct from H. pylori which has been described recently in human antral mucosa from patients with gastritis and may be of potential significance as a pathogen in man. The name "Gastrospirillum suis" is proposed for this bacterium. PMID- 2231674 TI - Bactericidal action of PD127,391, an enhanced spectrum quinolone. AB - The 4-quinolone PD127,391 displays a biphasic effect on Escherichia coli, Staphylococcus aureus and S. epidermidis in nutrient broth. It is as active as ciprofloxacin in terms of its optimum bactericidal concentration against E. coli. However, against staphylococci it is six times as active as ciprofloxacin or any other 4-quinolone previously investigated. Although protein and RNA synthesis are not required for bactericidal activity, cell division is essential. PMID- 2231675 TI - Plasmid profiles of Shigella dysenteriae type 1 isolates from Ethiopia with special reference to R-plasmids. AB - Plasmid profiles of 80 Shigella dysenteriae type 1 (Shiga's bacillus) strains, collected between 1974 and 1985 in Ethiopia, were examined. Strains with the dominant antibiotic-resistance (R-) type--resistance to ampicillin (A), chloramphenicol (C), streptomycin (S), sulphadiazine (Su) and tetracycline (T)- showed two distinct plasmid profiles (PP). Six plasmid bands were demonstrated in "Ethiopian strains" with PP-1A isolated between 1974 and 1982. In mating experiments with these strains, Escherichia coli K12 recipients showed plasmids pYH10a (72 Mda, atypical Inc FIme, coding for ACSSuT resistance). Eight plasmid bands were demonstrated in strains with PP-2A. These strains were first isolated in 1980 and carried plasmid pYH11a (40 Mda, Inc X, coding for ACT resistance). Strains with PP-2A were identical with a "Zairian strain" described elsewhere. Strains with R-type ACT were "Zairian strains" lacking the 5.1- and 4.2-Mda plasmids. Those with R-type CSSuT were temporally clustered in 1978-1980 and carried plasmid pYH12 (58 Mda, Inc B, coding for the same R-type). A trimethoprim resistant strain (Gimira strain) had a pattern of small plasmids similar to those of the "Zairian strain" and is probably a subclone of the latter. The fact that a limited number of plasmid profiles have remained constant over many years shows the limitation of plasmid profile analysis as an epidemiological tool. However, when the usual profile is known for a given area, identification of a distinctly different pattern becomes easy and epidemiologically useful. PMID- 2231676 TI - Plasmids and factors associated with virulence in environmental isolates of Vibrio cholerae non-O1 in Bangladesh. AB - Plasmid profiles and factors associated with toxigenicity in 51 strains of Vibrio cholerae non-O1 isolated from water samples collected in Bangladesh were analysed. Eleven (21.5%) strains were found to harbour at least one plasmid of 1.7-115 Mda; seven of these strains shared a 115-Mda plasmid. Six of 13 strains tested gave positive cytotoxic and enterotoxic responses. However, two non cytotoxic strains were enterotoxigenic. Only three of the six cytotoxic and enterotoxic strains caused haemagglutination of human erythrocytes which indicated that toxin production and haemagglutinating activity were unrelated in these V. cholerae non-O1 strains. Conjugal transfer assays demonstrated that the 115-Mda plasmid harboured by some of the toxigenic V. cholerae non-O1 strains carried genes coding for antibiotic resistance and cytotoxin production but not for enterotoxin production. However, this plasmid was also carried by non toxigenic strains. Some other strains carrying no plasmids or only small-mol.-wt plasmids, were found to be toxigenic. Therefore, toxin production is not plasmid mediated in all V. cholerae non-O1 strains. Regardless of their pathogenic potential, V. cholerae non-O1 strains possessed the capacity to grow in conditions of iron limitation and, under these conditions, synthesis of at least two new outer-membrane proteins was induced. PMID- 2231677 TI - Pathogenic factors of Pseudomonas cepacia isolates from patients with cystic fibrosis. AB - One hundred and nineteen isolates of Pseudomonas cepacia, 98 of which were from cystic fibrosis (CF) patients and 21 from environmental and other human sources, were examined for biochemical and exo-enzymatic properties that may contribute to the pathogenicity of this bacterium. The following characteristics were demonstrated significantly more frequently in isolates from CF patients than in control isolates: production of catalase, ornithine decarboxylase, valine aminopeptidase, C14 lipase, alginase and trypsin; reduction of nitrate to nitrite; hydrolysis of urea and xanthine; complete haemolysis on bovine red blood cells; cold-sensitive haemolysis on human red blood cells; greening of horse and rabbit red blood cells. The role of these factors in the pulmonary disease associated with cystic fibrosis is not clear. However, several factors which have been reported previously as being associated with pathogenic processes with other bacteria have now been described in P. cepacia. Additional factors not previously reported as "pathogenicity factors" are also described. PMID- 2231678 TI - The use of selective media for the isolation of Pseudomonas pseudomallei in clinical practice. AB - Ashdown's selective-differential agar medium, with or without preenrichment in selective broth, was evaluated for the isolation of Pseudomonas pseudomallei from 1972 clinical specimens obtained from 643 subjects in Northeast Thailand; 226 patients proved to have meliodosis. The use of Ashdown's medium significantly increased the frequency of recovery of P. pseudomallei from sites or specimens with an extensive normal flora (throat, rectum, wounds and sputum) as compared to the recovery on blood and MacConkey agars (p less than 0.01). The isolation frequency from throat, rectal and wound swabs was further increased by the use of the broth pre-enrichment. The colonial morphology of P. pseudomallei on Ashdown's medium was sufficiently characteristic to allow presumptive identification. With the use of these selective media it was possible to culture P. pseudomallei from throat swabs taken from 87% of the patients from whom the organism could also be isolated from corresponding tracheal aspirates or sputum specimens. P. pseudomallei was isolated from rectal swabs taken from 51 patients, the first time that faecal excretion of the organism has been demonstrated in man. The diagnosis of melioidosis would not have been confirmed bacteriologically in eight patients (3.5%) without the use of the selective media. It is suggested that, in areas endemic for melioidosis, all sputum specimens should be cultured on selective media, such as Ashdown's. For the investigation of clinically suspected cases of melioidosis, and for follow-up during treatment of the disease, the use of broth pre-enrichment is recommended for specimens obtained from sites with an extensive normal flora. PMID- 2231679 TI - Phagocytosis of Legionella pneumophila. PMID- 2231680 TI - Virulence of ten serogroups of Clostridium difficile in hamsters. AB - A slide agglutination technique identifying 10 serogroups of Clostridium difficile (A,B,C,D,F,G,H,I,K and X) has been described previously. In this study, we have used the hamster to compare the ability of the 10 serogroup reference strains to colonise and produce disease. Groups of four hamsters were each given a single intraperitoneal injection of either clindamycin or cefoxitin, and an oral challenge dose of C. difficile. The time taken to establish faecal colonisation and the length of survival after colonisation were monitored. All hamsters treated with cefoxitin became colonised by day 3 and those challenged with the cytotoxigenic strains of serogroups A,C,H and K developed colitis and died. Among those challenged with the non-toxigenic strains of groups B,D,I and X and the toxigenic strains of groups F and G, faecal colonisation was established without signs of disease. This demonstrates that there are differences in virulence even among toxigenic strains of C. difficile. The same phenomenon was observed after treatment with clindamycin but the pattern of colonisation was quite different with some strains. In the hamsters challenged with toxigenic strains of groups C and K and non-toxigenic strains of groups D and I, which are highly resistant to clindamycin, the response was the same as with cefoxitin. The results were different with strains which were susceptible to clindamycin. Some animals became colonised much later than those treated with cefoxitin but the mortality was similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231681 TI - The simian immunodeficiency virus (SIV) rev gene regulates env expression. AB - The rev gene product is a trans-acting nuclear regulatory protein that is essential for AIDS virus replication. To define the effect of the SIV rev gene on its gp160 expression, two SV40 constructs have been made: pBC17 is a rev+env+ construct, and pBD21 is a rev-env+ construct. After transfecting the constructs into COS-1 cells, RNA, protein, syncytium formation, and monoclonal antibody blocking assays were performed. The results indicated that the SIV rev gene positively influenced the level of full-length env mRNA and was required for expression of SIV gp160. PMID- 2231682 TI - Mutational analysis of simian immunodeficiency virus from African green monkeys and human immunodeficiency virus type 2. AB - We constructed ten mutants of simian immunodeficiency virus isolated from African green monkey (SIVAGM), and nine mutants of human immunodeficiency virus type 2 (HIV-2) in vitro. Their infectivity, cytopathogenicity, transactivation potential, virus RNA, and protein synthesis were examined by transfection and infection experiments. Mutations in three structural (gag, pol, env) and two regulator (tat, rev) genes abolished the infectivity of both viruses, but vpx, vpr (HIV-2), and nef were dispensable and mutant viruses were indistinguishable phenotypically from wild type virus. A vif mutant of HIV-2 showed poor infectivity in cell-free condition, whereas SIVAGM mutants grew equally well with wild type virus. In transient transfection assays, rev mutants derived from both viruses produced mainly small mRNA species and no detectable virus proteins and particles. Transactivation potential of tat mutants originated from both viruses was about three- to ten-fold less than that of respective wild type DNAs, generating small amounts of virus. PMID- 2231683 TI - Identification of SIV/SMM viral proteins that induce T cell response in experimentally infected rhesus macaques and naturally infected sooty mangabeys by the cellular western blot assay. AB - Initial studies have revealed subtle differences in the T cell proliferative response to whole SIV antigen in the peripheral blood mononuclear cells (PBMC) from sooty mangabeys and rhesus macaques. Preliminary findings utilizing the cellular Western blot assay are described. PMID- 2231684 TI - Antibody-dependent enhancement of SIV infection: further characterization and cross reactivity between macaque and sooty mangabey isolates. AB - Plasma from four rhesus macaques (Macaca mulatta), of which two were experimentally infected with the simian immunodeficiency virus (SIV) isolate SIVmac251, one with isolate SIVsmF236, and another with a SIVsmF236 molecular clone, SIVsmH-4, enhanced SIVmac infection of MT-2 cells. In addition to SIV positive plasma, infection-enhancement required complement, CD4, and CR2. Titers of infection-enhancing antibodies appeared to correlate with disease progression. The MT-2/SIVmac251 system should be useful in future studies of complement mediated, antibody-dependent enhancement of macaque and sooty mangabey SIV isolates. PMID- 2231685 TI - Molecular characterization of SIV in tissues from experimentally infected macaques. AB - Tissues from SIV-infected, immunodeficient macaques were analyzed by southern blot and polymerase chain reaction (PCR) amplification of env sequences. Provirus was readily detected in both lymphoid and non-lymphoid tissues by southern blot analysis. The majority of virus was in an unintegrated state. Analysis of envelope sequences by PCR revealed that tissues contain many distinct, but closely related genotypes; however, only a subset of these proviral genomes are recovered after tissue culture passage in human cell lines. Thus, tissue culture isolates of SIV do not represent the complete spectrum of genotypes in an infected macaque. PMID- 2231686 TI - Molecular characterization of simian lentiviruses from east African green monkeys. AB - Asymptomatic infection with simian lentiviruses (also called simian immunodeficiency viruses, or SIV) is common among feral African green monkeys. To characterize the range of SIV genetic diversity among infected African green monkeys, we have determined nucleotide sequences from complete or partial molecular clones of four distinct SIVagm isolates from Kenya and Ethiopia. The nucleotide and amino acid variability we observed among the SIVagm isolates was greater than the variability within any other group of primate lentiviruses. These data suggest that: a) African green monkeys have been infected with simian lentiviruses for many years; and b) novel and uncharacterized primate lentiviruses may exist in the feral African green monkey population in other parts of Africa. PMID- 2231687 TI - Sequence variability of simian immunodeficiency virus in a persistently infected rhesus monkey. AB - A juvenile rhesus monkey that was inoculated intravenously with molecularly cloned SIVmac239 became persistently infected. A modified polymerase chain reaction (PCR) procedure was used to specifically amplify full-length envelope (env) gene sequences from DNA extracted from peripheral blood mononuclear cells (PBMC), lymph node tissue, and cells infected with recovered virus at 69 and 93 weeks post-infection. Extensive sequence variability accumulated in vivo in spite of infection with molecularly cloned virus. In the central portion of env. sequence variability was largely confined to three discrete regions. PMID- 2231688 TI - Characterization of clones of HIV-1 infected HuT 78 cells defective in gag gene processing and of SIV clones producing large amounts of envelope glycoprotein. AB - Single-cell clones of HIV-1 (FRE-3) or SIV/Mne infected HuT 78 cells were obtained by plating dilutions of virally infected HuT 78 cells on a monolayer of sheep choroid plexus cells in 96-well microtiter plates. Several of these clones produce HIV-1 virus mutants that accumulate the gag precursor polyprotein and lack a functional protease. These protease-deficient viruses are non-infectious and consist of aberrant "immature" virus particles as determined by electron microscopy. Several SIV mutants are also described that produce large amounts of either the envelope glycoprotein gp120 or the nucleic acid binding gag protein. These mutants are useful for the purification of these retroviral proteins, in developing assays of protease inhibitors, and in preparing SIV envelope protein vaccines. PMID- 2231689 TI - Inoculation of Macaca fascicularis with simian immunodeficiency virus, SIVmne immunologic, serologic, and pathologic changes. AB - Previous studies had tested the susceptibility of two macaque species, Macaca nemestrina and M. mulatta, to infection with the primate lymphotropic lentivirus SIVmne. In this report we describe the results obtained after infecting eleven M. fascicularis with SIVmne. Six of the animals had previously been immunized with a recombinant vaccinia virus expressing the envelope gene of HIV-1. All eleven animals became seropositive. To date ten animals have died 43 to 155 weeks post infection of an AIDS-like disease. PMID- 2231690 TI - Experimental infection of timed-pregnant rhesus monkeys with simian immunodeficiency virus (SIV) during early, middle, and late gestation. AB - Ten rhesus monkeys were inoculated with SIV/DeltaB670 during various stages of gestation to determine factors predictive of transplacental infection. Two abortions associated with rapid disease occurred shortly after infection; uninfected infants were caesarean delivered from eight other females. SIV specific RNA accompanied by deciduitis was identified in the maternal portion of two placentas suggesting that opportunistic infections may promote entry of SIV into placental tissue. The lack of evidence for SIV infection of caesarean delivered infants suggests that fetal infection may often occur during parturition. PMID- 2231691 TI - Use of simian immunodeficiency virus for vaccine research. AB - Rhesus monkeys were immunized with purified, disrupted, noninfectious simian immunodeficiency virus (SIV) in adjuvant induced SIV neutralizing antibodies. Two of six previously vaccinated macaques were protected against infection when challenged with 200-1,000 animal infectious doses of uncloned, pathogenic SIV and both have remained free of signs of virus infection for 19 and 30 months. Prior vaccination appeared to be of benefit in decreasing the virus load and in delaying the onset of AIDS in animals that became infected. Nonetheless, two of four previously vaccinated monkeys that became infected following challenge eventually developed AIDS and died 505 and 538 days after infection. Thus, for a vaccine to be truly effective against AIDS, it may have to protect absolutely against initial infection. PMID- 2231692 TI - Gag precursors of HIV and SIV are cleaved into six proteins found in the mature virions. AB - During retroviral maturation gag precursors are proteolytically cleaved to mature gag proteins. The number of mature gag proteins and their order in the gag precursors of HIV-I3B, SIVMne (captive macaque isolate), and SIVCat (wild mangabey isolate) has been determined by N-terminal amino acid sequence analysis of mature gag proteins and alignment with predicted sequences of homologous gag precursors. For HIV-1 and SIVs maturation proteolysis results in six gag proteins and the gag precursor cleavage pattern is distinctive and different from cleavage patterns for all other known retroviruses. PMID- 2231693 TI - Nef genes of SIV. AB - Molecular clones of SIVmac were constructed that differed only in sequences within the nef gene. DEAE-transfection of viral DNA containing an open from of nef yielded virus that replicated with similar kinetics and to a similar extent in macaque peripheral blood lymphocyte (PBL) cultures as virus with a deletion or stop codon within nef. Rhesus monkeys that received each kind of molecularly cloned virus became infected. Our results additionally suggest that mutant forms of virus are selected in vitro while open, functional forms are selected in vivo. In animals infected with virus containing a stop codon within nef, reversion of the stop codon to a coding codon was demonstrated in five of five clones analyzed. These results indicate that nef is playing some role crucial to the virus life cycle in vivo. PMID- 2231694 TI - Molecular changes associated with replication of simian immunodeficiency virus in human cells. AB - The SIVmac239 infectious clone does not have a premature stop codon in its transmembrane protein (TMP) region and it produces full-length (41 kilodalton, kDa) TMP in macaque peripheral blood lymphocytes (PBL) in vitro and in vivo. However, viruses with truncated forms of TMP (28kDa) are selected during propagation in human cell types; truncated forms arise from point mutations, CAG (glutamine) to TAG (stop), in the viral genome. These results document molecular changes associated with adaptation of SIVmac for growth in human cells. PMID- 2231696 TI - Electrophysiology of cultured human lens epithelial cells. AB - The lens epithelial K+ conductance plays a key role in maintaining the lens ionic steady state. The specific channels responsible for this conductance are unknown. We used cultured lens epithelia and patch-clamp technology to address this problem. Human lens epithelial explants were cultured and after 1-4 passages were dissociated and used in this study. The cells from which we measured had a mean diameter of 31 +/- 1 microns (SEM, n = 26). The resting voltage was -19 +/- 4 mV (SEM, n = 10) and the input resistance was 2.5 +/- 0.5 G omega (SEM, n = 17) at 60 mV. Two currents were prominent in whole-cell recordings. An outwardly rectifying current was seen in nearly every cell. The magnitude of this current was a function of K+ concentration and was blocked by 3 mM tetraethylammonium. The instantaneous current-voltage relationship was linear in symmetric K+, implying that the outward rectification was due to gating. The current showed complex activation and inactivation kinetics. The second current seen was a transient inward current. This current had kinetics very similar to the traditional Na+ current of excitable cells and was blocked by 0.1 microM tetrodotoxin. In single-channel recordings, a 150-pS K+ channel and a 35-pS nonselective cation channel were seen but neither account for the macroscopic currents measured. PMID- 2231697 TI - Visualization and coding in three-dimensional image processing. AB - A system for calculating orthographic views of three-dimensional objects from a confocal microscope has been implemented in a high-level language. It is used on a regular basis in a number of projects and on different computers. The system enables the user to filter the original data and make a selection of which points and parts of the objects to show in a projective view. The information to be shown is coded in a compact format that is well suited for projection calculations. Several display principles were implemented that enhance different aspects of the objects. PMID- 2231698 TI - Measuring the forces acting during microtomy by the use of load cells. AB - The forces acting upon the cutting blade during microtomy can be accurately measured by using a load cell. From the information obtained, the optimal knife angles (rake, clearance and slant) can be determined. In addition, the speed of cutting and thickness of sections can also be optimized. The information obtained from the load cell additionally reveals variations in tissue composition which affect the cutting forces. This paper is a preliminary communication to illustrate the possible roles for a modified microtome in (a) the study of microtomy and (b) comparative studies of tissue density. PMID- 2231699 TI - Concentration of solutes during preparation of aqueous suspensions for cryo electron microscopy. AB - It is demonstrated that solutes are likely to be significantly concentrated under conditions commonly used to prepare vitrified aqueous suspensions for transmission electron microscopy. Muscle thick filaments in such suspensions were largely dissolved, probably due to an increase in salt concentration caused by evaporation of water immediately prior to freezing. The extent of solubilization indicated that salts had been concentrated by at least 50%. Simple tests showed that, under the conditions used, the rate of reduction in the height of a thin water layer was approximately 1 micron/s. Apparatus is described which reduces evaporation, by clamping the hydrated grid in a filter paper sandwich until just before it enters the ethane coolant. High-speed cine photography showed that, using this device, exposure of the thinned specimen to the atmosphere was approximately 200-fold less. Frozen-hydrated thick filaments prepared using the device had the expected length of about 1.6 microns. PMID- 2231700 TI - Improving access to pediatric health care in Mississippi. AB - Working under the Mississippi Postneonatal Death Impact Project, the Mississippi Chapter of the American Academy of Pediatrics, in conjunction with the State Department of Health, helped improve access to pediatric health care in Mississippi. This was accomplished by developing a statewide telephone information and referral service (telephone case management), enlisting primary care physicians to treat a limited number of children without specific compensation and staging a public awareness campaign. System barriers encountered were identified and interagency coordination and cooperation suggested. This effort could be easily replicated and expanded. PMID- 2231701 TI - Multiple pterygium syndrome: neuromuscular findings in a case. AB - A woman with multiple congenital joint deformities and webbing (multiple pterygium syndrome) is described. The electrophysiologic study revealed normal sensory and motor nerve conduction velocities. However, the compound muscle action potential amplitude and the voluntary motor unit size were reduced, suggesting a decrease in the number of muscle fibers. The muscle biopsy was otherwise unremarkable histologically and histochemically. Possible explanations for these findings are discussed. PMID- 2231702 TI - Correlation of urinary tract infection with urinary screening at the first antepartum visit. AB - Urinary tract infection contributes to the morbidity of pregnancy since 4-10 percent of antepartum patients have asymptomatic bacteriuria and 20-40 percent of these will result in pyelonephritis. A cost-effective outpatient assessment for asymptomatic bacteriuria in undelivered obstetric patients is described. In this study, 56 patients between 6-24 weeks gestation were assessed over a seven-month period by photometric urinary screening. This assessment was more accurate in identifying those patients with asymptomatic bacteriuria than prior history or symptoms. A 7 percent incidence of asymptomatic bacteriuria was noted with 75 percent being Escherichia coli and the remainder Klebsiella. Single-dose, oral antibiotic therapy was evaluated and resulted in no recurrences. Such screening for asymptomatic bacteriuria was felt to represent preventive and economic medical benefits. PMID- 2231704 TI - Medicare fee schedule. PMID- 2231703 TI - "Adopted standards for the regulation of medical waste" in health care facilities licensed by the Mississippi State Department of Health. PMID- 2231695 TI - Use of Xenopus oocytes for the functional expression of plasma membrane proteins. PMID- 2231706 TI - Hospital acted properly in revoking privileges. PMID- 2231705 TI - Severe movement disorder. PMID- 2231707 TI - Preliminary crystallographic analysis of trypanothione reductase from Crithidia fasciculata. AB - Trypanothione reductase, a flavoprotein disulfide reductase specific to trypanosomatid parasites, has been crystallized by vapor diffusion of a protein solution (10 mg/ml) against 22% polyethylene glycol (average Mr 8000) containing 100 mM-ammonium sulfate. Crystals of a size suitable for structure determination by X-ray diffraction have been obtained by seeding protein solutions with smaller crystals. The space-group is P21 (a = 60.9 A, b = 161.8 A, c = 58.4 A, beta = 99.1 degrees). The molecular mass and volume of the unit cell suggest that there is a dimer of the enzyme in the asymmetric unit, and this is confirmed by self rotation functions calculated using data to 4.5 A resolution. The crystals diffract to beyond 3 A resolution. Crystals of another P21 form (a = 91.3 A, b = 114.4 A, c = 92.0 A, beta = 141.3 degrees) are observed to grow under similar conditions. PMID- 2231708 TI - Narbonin, a 2 S globulin from Vicia narbonensis L. Crystallization and preliminary crystallographic data. AB - A seed globulin from Vicia narbonensis L. has been crystallized by vapour diffusion induced pH-shift. Crystals are suitable for high-resolution X-ray structural analysis and diffract to better than 1.5 A. Narbonin crystallizes in the monoclinic space group P21 with alpha = 46.9 A, b = 75.5 A, c = 50.9 A, alpha = gamma = 90 degrees, beta = 120.5 degrees. The protein consists of one polypeptide chain that does not coincide with the subunits of legumin or vicilin after SDS/polyacrylamide gel electrophoresis and has a relative molecular mass of about 33,000. PMID- 2231709 TI - Trigonal crystals of porcine mitochondrial aspartate aminotransferase. AB - Crystals suitable for X-ray analysis of porcine mitochondrial aspartate aminotransferase in the closed conformation were obtained after the apoenzyme was reconstituted with N-5'-phosphopyridoxyl-L-aspartate, an inhibitor in which the cofactor is covalently bound to the substrate. This results in a crystal form that has not been encountered previously in studies of aspartate aminotransferases. The crystals belong to the trigonal space group P3121 (or the enantiomeric P3221) with unit cell dimensions alpha = b = 202.0 A, c = 58.0 A, alpha = beta = 90 degrees, gamma = 120 degrees and contain one dimer in the asymmetric unit. PMID- 2231710 TI - Order-disorder phenomena in myelinated nerve sheaths. I. A physical model and its parametrization: exact and approximate determination of the parameters. AB - An algorithm is developed for the analysis of the X-ray scattering spectra of lamellar systems, by reference to a precise physical model. The model consists of identical planar lamellae (the motif), all parallel and stacked in a one dimensional crystal with four types of defect: stacking disorder, finite size of the crystallites, and presence of diffuse and blank scattering. In addition, the spectra are distorted by collimation aberrations. In order to evaluate the effects of these distortions, the following assumptions are made: (1) beyond some point Slimit the intensity curve can be expressed as a function of a (small) number of parameters; (2) the blank scattering, restricted to very small angles, can be identified and eliminated; and (3) the diffuse scattering is entirely defined by the values of idiff(h/D) at the lattice Sh = h/D (h is a positive integer less than or equal to DSlimit). These assumptions lead to an expression of the whole of the intensity curve as a function of a finite number of parameters: the average D and the variance sigma 2D of the repeat distance, the average number [N] of lamellae per crystallite, the set [idiff(h/D)] and the set [imotif(k/2D)] (where k is a positive integer), which defines the structure of the motif. An algorithm is proposed to determine the value of the various parameters. The derivation of the algorithm involves several operations: construction in real space of periodic functions whose motifs are step-sections of the autocorrelation function; expression in reciprocal space, and in terms of the experimental scattering curves, of the Fourier transform of those periodic functions; analysis of the properties of the two functions. The algorithm is tested using a variety of simulated scattering curves whose parameters [imotif(k/2D)], [idiff(2/D)], D, sigma D, [N] (and collimation distortions) are within the range commonly encountered in experimental conditions. The results show that the values of the parameters retrieved by the algorithms are very close to those used in the simulation. The calculations are fast and easy to implement on a computer. The main virtues of the algorithm are (1) to determine the values of all the parameters at once, eliminating most of the intermediate (and questionable) manipulations (separation of signal from noise, discrimination of overlapping reflections, integration of the intensities) and (2) to yield the continuous intensity curve of a single motif. PMID- 2231711 TI - Order-disorder phenomena in myelinated nerve sheaths. II. The structure of myelin in native and swollen rat sciatic nerves and in the course of myelinogenesis. AB - The algorithm described in the accompanying paper was applied to X-ray scattering experiments performed with rat sciatic nerves, either as a function of the age of the animal (4 to 30 days), or with adult nerves swollen in non-isotonic media. The results were all consistent with the model of disorder used in the theoretical treatment. The algorithm leads, in one step, from the data to the numerical values of the parameters, avoiding all intermediate manipulation. For each experiment a variety of parameters was determined: the average D and the variance sigma 2D of the repeat distance, the average number [N] of motifs per crystallite, the set [idiff(h/D)], which defines the diffuse scattering, the fraction alphaloose of myelin that does not belong to the compact sheaths, and the set [imotif (k/2D)], which suffices to define the continuous intensity curve of the motif imotif(s). Note the remarkable wealth of information, especially by contrast with conventional analyses which, as a rule, only yield the values of D and of the set [imotif(h/D)] (insufficient to determine the function imotif(s]. The function imotif(s) and the parameters D and sigma D (and thus the local structure of the myelin sheaths) were shown to be almost invariant in the course of myelinogenesis; what varies is mainly the total amount of myelin in the nerve and the number of membranes per sheath. Swelling agents have a dramatic influence on the X-ray scattering spectra, but in spite of the conspicuous variation of D, sigma D and [N] the structure of the motif is invariant. The structure of the motif was shown to be quite different in the native and in the swollen samples; the stacking disorder appears to involve mainly the cytoplasmic space in native myelin, the external space in swollen nerves. The very notion of electron density profile, when disorder is present, is discussed. Two criteria were proposed to select the "best" signs of the reflections: two sets came out at almost the same rank, one corresponding to Caspar & Kirschner's the other to Worthington & McIntosh's proposals, neither of which can be ruled out according to the criteria used in this work. PMID- 2231712 TI - Basic local alignment search tool. AB - A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity. PMID- 2231713 TI - Solution conformation of purine-pyrimidine DNA octamers using nuclear magnetic resonance, restrained molecular dynamics and NOE-based refinement. AB - The solution structures of two alternating purine-pyrimidine octamers, [d(G-T-A-C G-T-A-C)]2 and the reverse sequence [d(C-A-T-G-C-A-T-G)]2, are investigated by using nuclear magnetic resonance spectroscopy and restrained molecular dynamics calculations. Chemical shift assignments are obtained for non-exchangeable protons by a combination of two-dimensional correlation and nuclear Overhauser enhancement (NOE) spectroscopy experiments. Distances between protons are estimated by extrapolating distances derived from time-dependent NOE measurements to zero mixing time. Approximate dihedral angles are determined within the deoxyribose ring from coupling constants observed in one and two-dimensional spectra. Sets of distance and dihedral determinations for each of the duplexes form the bases for structure determination. Molecular dynamics is then used to generate structures that satisfy the experimental restraints incorporated as effective potentials into the total energy. Separate runs start from classical A and B-form DNA and converge to essentially identical structures. To circumvent the problems of spin diffusion and differential motion associated with distance measurements within molecules, models are improved by NOE-based refinement in which observed NOE intensities are compared to those calculated using a full matrix analysis procedure. The refined structures generally have the global features of B-type DNA. Some, but not all, variations in dihedral angles and in the spatial relationships of adjacent base-pairs are observed to be in synchrony with the alternating purine-pyrimidine sequence. PMID- 2231714 TI - Temperature dependence of dynamics of hydrated myoglobin. Comparison of force field calculations with neutron scattering data. AB - Molecular dynamics is used to probe the atomic motions of the carboxy-myoglobin protein as a function of temperature. Simulations of 150 picoseconds in length are carried out on the protein at 20, 60, 100, 180, 220, 240, 260, 280, 300, 320 and 340 K. The simulations attempt to mimic neutron scattering experiments very closely by including a partial hydration shell around the protein. Theoretical elastic, quasielastic and inelastic neutron scattering data are derived from the trajectories and directly compared with experiment. Compared to experiment, the simulation-derived elastic scattering curves show a decrease in intensity as a function of the scattering wavevector, q2. The inelastic and quasielastic spectra show that the inelastic peak is shifted to lower frequency than the experimental value, while quasielastic behavior is in good agreement with experiment. This suggests that the theoretical model is too flexible in the harmonic limit (low temperature), but accurately reproduces high-temperature behavior. Time correlation functions of the intermediate scattering function are determined. At low temperature there is one fast decay process, and at high temperatures there is an additional slow relaxation process that is due to quasielastic scattering. The average atomic fluctuations show that the protein behaves harmonically at low temperatures. At approximately 210 K, a glass-like transition in atomic fluctuations is seen. Above the transition temperature, the atomic fluctuations exhibit both harmonic and anharmonic behavior. Comparison of protein mobility behavior with experiment indicate the fluctuations derived from simulations are larger in the harmonic region. However, the anharmonic region agrees very well with experiment. The anharmonicity is large at all temperatures, with a gradual monotonic increase from 0.5 at 20 K to greater than 0.7 at 340 K without a noticeable change at the glass transition temperature. Heavy-atom dihedral transitions are monitored as a function of temperature. Trends in the type of dihedral transitions that occur with temperature are clearly visible. Dihedral transitions involving backbone atoms occur only above the glass transition temperature. The overall protein behavior results suggest that at low temperatures there is purely vibrational motion with one fast decay process, and above the glass transition temperature there is more anharmonic motion with a fast and a slower relaxation process occurring simultaneously.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231715 TI - Hydrogen bond stereochemistry in protein structure and function. AB - Fifty high resolution protein structures from the Brookhaven Protein Data Bank have been analyzed for recurring motifs in hydrogen bond stereochemistry. Although an exhaustive analysis of hydrogen bond statistics has been presented by Baker & Hubbard, a detailed stereochemical analysis of classical donor (N-H, O-H, or S-H) and acceptor (N:, O:, or S:) structure within proteins is lacking. Here, we describe the preferential hydrogen bond stereochemistry for the side-chains of glutamate and aspartate (carboxylate), glutamine and asparagine (carboxamide), arginine (guanidinium), histidine (imidazole/imidazolium), tryptophan (indole), tyrosine (phenolic hydroxyl), lysine (ammonium), serine and threonine (alkyl hydroxyl), cysteine (thiol), methionine (thioether) and cystine (disulfide). Preferential hydrogen bond stereochemistry is governed by (1) the electronic configuration of acceptor atoms, (2) the steric accessibility of donor atoms and (3) the conformation of amino acid side-chains. Applications of hydrogen bond stereochemistry are useful in the interpretation of protein structure, function and stability. Additionally, this stereochemistry is a prerequisite to the interpretation of protein-other molecule recognition and biological catalysis. PMID- 2231716 TI - Preliminary crystal structure analysis of an Fab specific for a Salmonella O polysaccharide antigen. AB - The Fab from an IgG1, lambda murine monoclonal antibody with specificity for the O-polysaccharide antigen of Salmonella typhimurium has been crystallized in the absence and presence of hapten. The conditions for crystal growth were vapor diffusion equilibration with 16 to 23% polyethylene glycol 8000 solutions. Data have been collected from crystals of the complex in space group P212121, a = 60.6 A, b = 111.3 A, c = 61.1 A, and refinement of a molecular replacement solution is underway. PMID- 2231718 TI - Binding of the regulatory protein VirG to the phased signal sequences upstream from virulence genes on the hairy-root-inducing plasmid. AB - The VirG protein is a positive regulator for the virulence genes of which expression is induced by a plant factor, and is essential for Agrobacterium pathogenicity on dicotyledonous plants. The VirG protein of the hairy-root inducing plasmid A4 was overproduced in Escherichia coli cells, and purified to homogeneity. DNase I footprinting experiments revealed that the purified VirG protein was bound to the upstream region of virulence genes including the phased vir box sequences, which had been presumed to be the VirG recognition signal from the sequence analysis. In dimethyl sulfate footprinting, the VirG protein specifically protected the guanine residues within every vir box sequence. It was concluded that the VirG protein was bound to the phased vir box sequences from the major groove along one side of double-helical DNA. PMID- 2231717 TI - Characterization of the Escherichia coli araFGH and araJ promoters. AB - The identities of two cloned, arabinose-inducible promoters were tested by hybridizing promoter DNA fragments with restriction digests of chromosomal DNA containing Mudlac phage inserted in either araFGH or in araE transport operons. One promoter, thought to be araE, is within 10(3) base-pairs of a Mudlac insertion in the araE gene. The second promoter was not found within several thousand base-pairs of either of the known transport genes. This promoter is now named araPJ (araJ). The DNA sequence of the fragment containing the araFGH promoter was determined. The start site of transcription in vivo was located to within +/- 1 base-pair (bp) by S1 nuclease mapping. DNase 1 footprinting revealed that, in comparison with the araBAD and araE promoters, the locations of the AraC and cyclic AMP receptor protein (CRP) binding sites are reversed with CRP lying between AraC and RNA polymerase. The central location of the CRP binding site may explain why the araFGH promoter is more catabolite sensitive than the other ara promoters. AraC and CRP were both required for maximal transcription in vitro, although a low level of transcription was detected with CRP alone. S1 nuclease mapping of mRNA-DNA hybrids from the araJ promoter located the transcription start point to within #/- 3 bp, and demonstrates that the promoter is dependent upon AraC protein and CRP in vivo. DNase footprinting showed that the location of the AraC protein binding site on araJ is adjacent to the RNA polymerase site, as seen at the araBAD and araE promoters. Two CRP sites were observed; one is upstream from the AraC site and one is downstream from the transcription start site. PMID- 2231719 TI - Novel mutants of elongation factor G. AB - A novel mutant form of elongation factor G (EF-G) in Escherichia coli is described. This variant EF-G restricts reading frame errors by a factor of 2 to 3 in vivo at two different positions in a lacIZ fusion. In addition, a conventional fusidic acid resistant (fusR) mutant of EF-G was compared with the restrictive mutant. Both mutants were characterized in vitro in a steady-state poly(U) translating system. The data indicate that the restrictive EF-G variant has an altered interaction with the ribosome both in vivo and in vitro. In contrast, the conventional fusR variant is altered in its interaction with GTP, which is evident in vitro. PMID- 2231720 TI - Structure of adenovirus fibre. I. Analysis of crystals of fibre from adenovirus serotypes 2 and 5 by electron microscopy and X-ray crystallography. AB - An analysis by electron microscopy in amorphous ice and X-ray diffraction of four types of three-dimensional crystals of adenovirus fibre is presented. Fibre from adenovirus type 2 (Ad2) crystallizes in two forms depending on whether it is native or cleaved near the N terminus at Tyr17. Fibre from Ad5 also crystallizes in two forms, both of which contained fibre cleaved at Tyr17. Analysis of the packing of the fibres in each of these crystals suggests that the overall length of the fibre may be considerably longer (about 350 to 370 A) than previously reported. Crystals of cleaved Ad2 fibre are of sufficient quality to be characterized by X-ray diffraction. They are of space group C2 and cell dimensions a = 134.4 A, b = 77.6 A, c = 539.4 A, beta = 92.7 degrees. These crystals are remarkable in that, despite being monoclinic, the ab plane forms a perfect hexagonal lattice. This is explained by a trigonal packing of the trimeric fibre heads in the crystal. A similar feature is found for one type of Ad5 crystal, although the hexagonal lattice is 12% smaller. The crystals of cleaved Ad2 show very strong meridional intensity at a Bragg spacing of 4.4 A and weaker diffuse intensity corresponding to layer-lines of spacing 26.4 A. This must reflect the quasiperiodicity of the structure of the fibre shaft, which is apparent in the primary sequence. The occurrence of these features combined with the new determination of the length of the fibre (see also the accompanying paper) require a reappraisal of the cross-beta model of the fibre shaft proposed by Green et al. PMID- 2231721 TI - Structure of adenovirus fibre. II. Morphology of single fibres. AB - Adenovirus type 2 fibres in crystals appear to be significantly longer than found previously (accompanying paper). We therefore examined isolated fibre by electron microscopy and measured a length of 370 A, consistent with the length found in the crystals. The specific N-terminal structure of the fibre caused a heterogeneity in the length that may at least partially explain the values of 280 to 310 A published previously. Green et al. described a 15 amino acid repeat in the primary structure of the shaft of the fibre thought to be associated with the specific three-dimensional folding of the shaft. We compared the adenovirus type 2 (with 22 repeats) and type 3 (with 6 repeats) fibre lengths and derived a contribution of 13.2 A to the length of the shaft per 15 amino acid repeat. Specific morphological features of the fibre are discussed in relation to its amino acid sequence. PMID- 2231722 TI - Studies of synthetic helical peptides using circular dichroism and nuclear magnetic resonance. AB - We have designed a set of 17-residue synthetic peptides to be monomeric helices in aqueous solution. Circular dichrosim experiments indicate the presence of helical structure in aqueous solution at low temperature and low pH. The two dimensional nuclear magnetic resonance results for one of the peptides show a segment of ten residues which clearly meets all of the criteria for the existence of helical structure at both 5 degrees C and 15 degrees C. The first four residues of the peptide are in a largely extended conformation. Calculations suggest that residues 5 through 14 are significantly helical at 5 degrees C. When the temperature is increased, circular dichroism spectra indicate that the helical content decreases. At 15 degrees C, the 3JN alpha coupling constants increase in the helical region, indicating an increase in motion or conformational averaging in the helical segment. None of the peptides has pH titration behavior consistent with salt bridge stabilization of helical conformation. Our data lend themselves to interpretation with the helix dipole model and specific side-chain interactions. When the N and C termini charges are removed the helical content of the peptides increases. The amount of helicity increases as the pH is lowered, due to the ionization of His16. Much of the helical stabilization appears to be due to a specific side-chain interaction between His16 and Tyr12. PMID- 2231723 TI - Three-stranded paranemic joints: architecture, topological constraints and movement. AB - The RecA and SSB proteins will catalyze the joining of two DNA molecules containing homologous sequences but lacking homologous ends in a reaction termed paranemic joining. The absence of homologous ends can be achieved by (1) pairing two circular DNAs or (2) using linear DNA(s) with ends lacking homology to the pairing partner. Here we have used electron microscopy (EM) to examine such pairings. Circular M13 single-stranded (ss) DNA enveloped by RecA protein into a presynaptic filament was paired with linear M13mp7 double-stranded (ds) DNA containing non-M13 sequences at its ends. Joint complexes were frequently seen in which the dsDNA was joined with the presynaptic filament over several kilobase (10(3) bases) lengths of the dsDNA. In this region, the presynaptic filament appeared disorganized as contrasted to the customary helical structure of the filament containing only a single strand of DNA. The same ultrastructure, but with greater detail, was observed when the samples were prepared for EM without fixation using a new method of fast-freezing and freeze-drying. EM immunogold staining demonstrated the presence of SSB protein in the disorganized region containing all three strands, but not in the regular helically arranged region. Psoralen photo-crosslinking of the DNA in the joint complexes revealed that the three DNA strands were in close proximity only over a single short (200 to 300 base-pairs) region. The joining of nicked circular M13 dsDNA and presynaptic filaments containing circular M13 ssDNA resulted in the intertwining of the dsDNA about the circular presynaptic filament. The joints produced in this case were short, as was the single region of psoralen photo-crosslinking of the three DNA strands. A model of how these long three-stranded joints form is presented involving the movement of a short "true" paranemic joint along the presynaptic filament. PMID- 2231724 TI - 2.2 A resolution structure analysis of two refined N-acetylneuraminyl-lactose- wheat germ agglutinin isolectin complexes. AB - The crystal structures of complexes of isolectins 1 and 2 of wheat germ agglutinin (WGA1 and WGA2) with N-acetylneuraminyl-lactose (NeuNAc-alpha(2-3)-Gal beta(1-4)-Glc) have been refined on the basis of data in the 8 to 2.2 A resolution range to final crystallographic R-factors of 17.2% and 15.3% (Fo greater than 1 sigma), respectively. Specific binding interactions and water association, as well as changes in conformation and mobility of the structure upon ligand binding, were compared in the two complexes. The temperature factors (B = 16.3 A2 and 18.4 A2) were found to be much lower compared with those of their respective native structures (19 to 22 A2). Residues involved in sugar binding, dimerization and in lattice contacts exhibit the largest decreases in B value, suggesting that sugar binding reduces the overall mobility of the protein molecules in the crystal lattice. The binding mode of this sialyl-trisaccharide, an important cell receptor analogue, has been compared in the two isolectins. Only one of the two unique binding sites (4 per dimer), located in the subunit/subunit interface, is occupied in the crystals. This site, termed the "primary" binding site, contains one of the five amino acid substitutions that differentiate WGA1 and WGA2. Superposition of the refined models in each of the independent crystallographic environments indicates a close match only of the terminal non-reducing NeuNAc residue (root-mean-square delta r of 0.5 to 0.6 A). The Gal-Glc portion was found to superimpose poorly, lack electron density, and possess high atomic thermal factors. In both complexes NeuNAc is stabilized through contact with six amino acid side-chains (Ser114 and Glu115 of subunit 1 and Ser62, Tyr64, Tyr(His)66 and Tyr73 of subunit 2), involving all NeuNAc ring substituents. Refinement has allowed accurate assessment of the contact distances for four hydrogen bonds, a strong buried non-polar contact with the acetamido CH3 group and a large number of van der Waals' interactions with the three aromatic side-chains. The higher affinity of N-acetylneuraminyl-lactose observed by nuclear magnetic resonance studies for WGA1 can be explained by the more favorable binding interactions that occur when residue 66 is a Tyr. The tyrosyl side-chain provides a larger surface for van der Waals' stacking against the NeuNAc pyranose ring than His66 and a hydrogen bond contact with Gal (C2-OH), not possible in WGA2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231725 TI - Protonated polypurine/polypyrimidine DNA tracts that appear to lack the single stranded pyrimidine loop predicted by the "H" model. AB - Three synthetic oligomers: 5'd(AG)8.dA.d(CT)(8)3'(A), 5'd(TC)7.d(TTA).d(GA)(8)3'(B) and d(GA)17(C) were cloned into the plasmid vector p915 in order to study the effects of sequence symmetry on pH-dependent structural transitions in polypurine/polypyrimidine DNA. When present in linear molecules all three sequences undergo transitions to protonated states. These are kinked to different degrees as determined by a non-denaturing gel mobility shift assay. Chemical probe analysis shows that the protonated states adopted by the linear forms of A and C exhibit certain features which have been regarded as indicating partially triple stranded "H" transition structures. The chemical reactivities of the transition structure adopted by linear molecule B and certain features of those exhibited by the transition structures of linear molecules A and C do not conform to the predictions of the "H" model. PMID- 2231726 TI - Deoxymyoglobin studied by the conformational normal mode analysis. II. The conformational change upon oxygenation. AB - The conformational change taking place in myoglobin concomitantly with the observed geometrical change at the heme-His(F8) linkage upon oxygenation is studied by normal mode analysis, which is based on the quadratic approximation of the conformational energy function. The heme-globin interaction energy increases for this change by 8.114 kcal/mol when both the heme group and the globin molecule are held rigid. When they are permitted flexibility, the interaction energy relaxes by 7.038 kcal/mol, and the difference (1.076 kcal/mol) is distributed as strain energy within the molecule. This increase is the work necessary for the heme group to move against the force exerted by the globin. If the force is assumed to be invariable during this move, the work is small, 0.276 kcal/mol, meaning that the force is strongly variable. Furthermore, this means that the heme group is located near the equilibrium point of the potential energy of the heme-globin interaction. The change in the localized strain energy stored in the force field at the linkage between the heme and the imidazole of HisF8 is estimated to be of the same order of magnitude as the distributed energy. The largest atomic displacements are observed at the region from the F helix to the beginning of the G helix, and secondary large displacements occur at several regions, i.e, the A helix, from the C helix to the CD corner, the E helix, and the C-terminal side of the H helix. All of these regions have strong dynamic interactions with the heme group, either directly or indirectly. Their secondary structures show complex deformations. In other parts, relatively rigid segments undergo rotational and/or bending changes in a way consistent with the large changes described above and close atomic packing within the molecule. The calculated conformational change is decomposed to vibrational normal modes of deoxymyoglobin. The magnitude of the conformational change, measured by the mass weighted mean-square atomic displacement, is accounted for up to 92.0% by the 151 normal modes with frequencies lower than 40 cm-1. In descending order of contribution, the first six modes, each of which has a frequency lower than 12 cm 1, account for up to 57.4%. This means that the functionally important conformational change can well be expressed in terms of a relatively small number of collective low frequency normal modes. PMID- 2231728 TI - 2.9 A resolution structure of the N-terminal domain of a variant surface glycoprotein from Trypanosoma brucei. AB - The variant surface glycoprotein (VSG) of Trypanosoma brucei forms a coat on the surface of the parasite; by the expression of a series of antigenically distinct VSGs in the surface coat the parasite escapes the host immune response. The 2.9 A resolution crystal structure of the N-terminal domain of one variant, MITat 1.2, has been determined. The structure was solved using data collected from two crystal forms. Initially a partial model was built into an electron density map based on multiple isomorphous replacement phases and improved by phase combination methods. Subsequently this model was used to obtain the molecular replacement solution for a second crystal form, providing starting phases which were refined using 2-fold non-crystallographic symmetry averaging. The current model includes 362 residues and has been refined using X-PLOR to an R value of 0.22 for data between 7 and 2.9 A. The molecule is a dimer, approximately 100 A long, having an asymmetrical cross section with maximum dimensions of approximately 40 A x 60 A. Two long, approximately 70 A, alpha-helices from each monomer pack together to form, with several other helices, a core helix bundle that extends nearly the full length of the molecule. The "top" of the protein, which in the surface coat may be exposed to the external environment, is formed from the ends of the two long helices, a short three-stranded beta-sheet, and a strand having irregular conformation that packs above these secondary structure elements. Two conserved disulfide bridges are in this part of the molecule. Several elements of the MITat 1.2 sequence, which contribute to the formation of the helix bundle structure, have been identified. These elements can be found in the sequences of several different VSGs, suggesting that to some extent the VSG structure is conserved in those variants. PMID- 2231727 TI - Structure of oncomodulin refined at 1.85 A resolution. An example of extensive molecular aggregation via Ca2+. AB - The crystal structure of oncomodulin, a 12,000 Mr protein isolated from rat tumours, has been determined by molecular replacement using the carp parvalbumin structure as a starting model. Refinement was performed by cycles of molecular fitting and restrained least-squares, using area-detector intensity data to 1.85 A resolution. For the 5770 reflections in the range 6.0 to 1.85 A, which were used in the refinement, the crystallographic R-factor is 0.166. The refined model includes residues 2 to 108, three Ca2+ and 87 water molecules per oncomodulin molecule. The oncomodulin backbone is closely related to that of parvalbumin; however, some differences are found after a least-squares fit of the two backbones, with root-mean-square (r.m.s.) deviations of 1 to 2 A in residues 2 to 6, 59 to 61 of the CD loop, 87, 90 and 108. The overall r.m.s. deviation of the backbone residues 5 to 108 is 0.62 A. Each of the two Ca2+ atoms that are bound to the CD and EF loops is co-ordinated to seven oxygen atoms, including one water molecule. The third Ca2+ is also seven-co-ordinated, to five oxygen atoms belonging to three different oncomodulin molecules and to two water molecules which form hydrogen bonds to a fourth oncomodulin; thus, this intermolecular Ca2+ and its equivalents interlink the molecules into zigzag layers normal to the b axis with a spacing of b/2 or 32.14 A. No such extensive molecular aggregation has been reported for any of the related Ca-binding regulatory proteins of the troponin-C family studied thus far. The Ca-O distances in all three polyhedra are in the range 2.07 A to 2.64 A, indicating tightly bound Ca polyhedra. PMID- 2231729 TI - Mutants of pheV in Escherichia coli affecting control by attenuation of the pheS, T and pheA operons. Two distinct mechanisms for de-attenuation. AB - Two mutants of pheV, a gene coding for tRNA(Phe) in Escherichia coli, were previously isolated because they affect attenuator control of the pheS, T operon when the mutant pheV genes are carried by the plasmid pBR322. We show that the two mutants (A44 and A46) affect attenuator control by different mechanisms. The effect of mutant A44 on pheS, T expression can be progressively decreased by overproduction of Phe-tRNA synthetase, consistent with the mutant tRNA acting as a competitive inhibitor of the enzyme. By contrast, the effect on attenuation of mutant A46 increases with overproduction of Phe-tRNA synthetase, indicating that the mutant must be charged to affect attenuation; we propose that this mutant affects translation directly and causes derepression by competing with wild-type tRNA in translation of the attenuator region leader peptide. Mutant A46 but not mutant A44 leads to further de-attenuation in a miaA background. The presence of two different mechanisms for de-attenuation is further indicated by the finding that a second attenuator controlled by Phe codon translation, from the pheA operon, is affected quite differently by the mutant tRNAs. Finally, experiments involving the introduction of the mutations A44 and A46 into an amber suppressor derived from tRNA(Phe) suggest that both species can function in protein synthesis but with reduced efficiency; mutant A46 is less efficient than mutant A44, consistent with a defect in elongation. PMID- 2231730 TI - Average orientation of aromatic residues in proteins determined from linear dichroism spectroscopy. A comparison of results on bovine gamma-crystallins with X-ray data. AB - The structures of the two very closely related proteins, bovine gamma II- and gamma IVa-crystallin have been studied by means of near-ultra-violet linear dichroism spectroscopy on squeezed polyacrylamide gel systems. The crystallin spectra are discussed in terms of the spectra of the aromatic chromophores present in these proteins and provide detailed information on the average orientation of these residues in the proteins. A comparison of our results with information based on crystallographic X-ray experiments shows excellent agreement, reflecting even some of the minor differences between the two proteins studied. Since linear dichroism measurements as performed here take a few days only, and can be done on most aqueous protein solutions, linear dichroism spectroscopy may give a valuable contribution to structural studies on proteins. PMID- 2231732 TI - Deoxymyoglobin studied by the conformational normal mode analysis. I. Dynamics of globin and the heme-globin interaction. AB - Dynamic properties of deoxymyoglobin are studied theoretically by the analysis of conformational fluctuations. Root-mean-square atomic fluctuations and distance fluctuations between different segments reveal the mechanical construction of the molecule. Eight alpha-helices behave as relatively rigid bodies and corner regions are more flexible, showing larger fluctuations. More particularly, corner regions EF and GH are specific in that flanking alpha-helices extend their rigidity up to a point in the corner region and the two rigid segments are connected flexibly at that point. The FG corner is exceptional. A segment from the F helix to the beginning of the G helix, in which the FG corner is included, becomes relatively rigid by means of strong interactions with the heme group. The whole myoglobin molecule is divided into two large units of motion, one extending from the B to the E helix, and the other from the F to the H helix. These two units are connected covalently by the EF corner. However, dynamic interactions between these two units take place mainly through contacts between helices B and G and not through the EF corner. From correlation coefficients between fluctuational motions of residues and the heme group, 55 residues are identified as having strong dynamic interactions with the heme moiety. Among them, 18 residues in the three segments, one consisting of residues from the C helix to the CD corner, a second consisting of the E helix, and a third from the F helix to the beginning of the G helix, are in close contact with the heme group. Twenty two of the 55 residues are within four residues of the 18 residues in their sequential residue number and are more than 3 A away from the heme group. The other 15 residues are located further in the sequential residue number and are all found in helices A and H. They are more than 6 A away from the heme group. By the use of correlation coefficients of fluctuations between residues, it is found that dynamic interaction with the heme group is transmitted to the A helix and the beginning of the H helix in the direction Leu(E15)----[Val(All) and Trp(A12)]. The transmission to the C-terminal end of the H helix is mediated by a long segment, from the end of the EF corner to the beginning of the G helix, that lies on the heme group and has close contacts over a wide range.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231731 TI - Replacement of the Escherichia coli trp operon attenuation control codons alters operon expression. AB - To test features of the current model of transcription attenuation in amino acid biosynthetic operons, alterations were introduced into the trp operon leader region and expression of the mutated operons was examined in miaA and miaA+ Escherichia coli strains that lacked the trp repressor. The miaA mutation prevents modification of the adenosine residue immediately 3' of the anticodon of tRNAs that interact with codons beginning with uridine. The undermodified tRNA(Trp) in miaA strains is thought to increase readthrough at the trp attenuator by slowing ribosome movement over two tandem Trp codons in the 14 codon leader peptide coding region. The rate of translation of these two "control codons" is thought to be the key step in determining the extent of transcription attenuation in the trp leader region. Sequential deletion of trpL DNA specifying the leader peptide initiation region, RNA segment 1, RNA segment 2 and RNA segment 3 alternately decreased and increased trp operon expression, a result consistent with previous findings in another bacterium and the generally accepted model for transcription attenuation. Replacement of the tandem Trp control codons by AGG-UGC (Arg-Cys) codons eliminated the miaA-dependent increase in transcription readthrough. Replacement of the Trp control codons by AGG-UGA (Arg stop) codons caused complete readthrough at the trp attenuator as well as abolishing the miaA effect. Presumably, the ribosome terminating translation at the new UGA codon mimics the effect of a stalled ribosome at the Trp control codons. This finding suggests that ribosome dissociation at some stop codons is slow relative to the time required for transcription of the trp leader region. Thus, most ribosomes translating the trp leader peptide coding region may remain attached to the natural UGA stop codon until after the attenuation decision is made. The interpretation supports models for trp operon attenuation in which the elevated basal level readthrough is determined by occasional ribosome release prior to synthesis of the 3:4 terminator hairpin. PMID- 2231733 TI - Improved post-ischemic ventricular recovery in the absence of changes in energy metabolism in working rat hearts following heat-shock. AB - We have previously demonstrated that induction of the heat-shock response in rats results in improved recovery of isolated Langendorff-perfused rat hearts subjected to low-flow ischemia followed by reperfusion (Currie et al., 1988). The mechanisms underlying this protective effect of heat-shock are uncertain although the protection was associated with enhanced content of the antioxidant enzyme catalase but not superoxide dismutase or glutathione peroxidase (Currie et al., 1988). Various investigators have suggested the importance of improved energy metabolism in determining recovery following ischemia (Pasque and Wechsler, 1984; Haas et al., 1984; Devous and Lewandowski, 1987). We therefore examined, using a working rat heart model subjected to 10 or 15 min zero flow ischemia whether changes in energy metabolites could account for the protective effect of the heat shock response. Hearts perfused 24 h after induction of heat-shock failed to demonstrate significant improvement of recovery following 10 min ischemia, however recovery was significantly enhanced in hearts reperfused after 15 min ischemia. Ischemia produced a depression in both ATP and creatine phosphate (CP) content whereas a moderate elevation in ADP and AMP and a marked increase in tissue lactate were evident. These changes were unaffected by prior heat-shock treatment. For both durations of ischemia tissue metabolites were determined during early (5 min) and late (30 min) reperfusion. Although partial recovery in high energy phosphates and a return of ADP, AMP and lactate to near-normal levels were evident, no differences in energy products were observed between hearts from normal or heat-shocked animals, in spite of significantly enhanced recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231734 TI - Role of oxygen free radicals generated by blood monocytes and neutrophils in the pathogenesis of rheumatic fever and rheumatic heart disease. AB - The generation of oxygen free radicals by peripheral blood monocytes and neutrophils of patients with rheumatic fever and rheumatic heart disease has been studied using luminol enhanced chemiluminescence technique. Five groups of patients; acute rheumatic fever, recurrence of rheumatic activity, chronic rheumatic heart disease, acute pharyngitis and normal controls were studied. In all groups except the controls, measurements were made on 0, 15, 90 and 180 days. The chemiluminescence was measured in response to streptococcal membrane antigen, carbohydrate antigen and latex as triggering agents. Chemiluminescent response of monocytes, as well as, neutrophils was significantly higher (P less than 0.01) in acute rheumatic fever and recurrence of rheumatic heart disease as compared to patients with acute pharyngitis and chronic rheumatic heart disease through the study period and with all the triggering agents. A significant decline (P less than 0.001) in chemiluminescence was observed from day 0 to day 180 in the acute rheumatic fever, recurrence of rheumatic heart disease and pharyngitis patients while no such change, was observed in the chronic rheumatic heart disease group. This study raises the possibility that these phagocytic cells, which infiltrate the myocardium, may have a role in the pathogenesis of cardiac disease seen in patients with rheumatic heart disease, through the generation of oxygen free radicals. PMID- 2231735 TI - Ischemia and reperfusion induced multilamellar vesicles in isolated rabbit hearts: time correlation between morphometric data and metabolic alterations. AB - In normoxic hearts a limited number of multilamellar vesicles was found in both endothelial cells and myocytes. The total number of multilamellar vesicles observed in myocytes, particularly those extruded from mitochondria, significantly increased in hearts rendered ischemic for at least 60 mins. The number of multilamellar vesicles extruded from sarcolemma was increased in hearts reperfused after this period of ischemia. The number of multilamellar vesicles in or adjacent to lipid droplets was independent of the duration of ischemia. Multilamellar vesicles were similar in size and periodicity of the lamellae. It is proposed that the number of multilamellar vesicles can be used to quantitate ischemic membrane injury. The formation of multilamellar vesicles was significantly related in time to (a) the accumulation of arachidonic acid and total fatty acids; (b) a decrease in the tissue content of ATP and (c) the release of lactate dehydrogenase (LDH). No significant alterations in the total tissue content of triacylglycerols and phospholipids were detected. The amount of arachidonic acid accumulated in the hearts reflects the degradation of only a minor fraction of the phospholipid pool. Assuming a close relationship between phospholipid degradation, induction of multilamellar vesicles and loss of cellular integrity, the present findings might indicate that the loss of a small part of phospholipids might have serious pathophysiological consequences, as indicated by the morphological changes in cellular membranes and the release of cytoplasmic macromolecules. PMID- 2231736 TI - Oxygen radical-mediated injury of myocytes-protection by propranolol. AB - UIe effects of propranolol and atenolol on free radical mediated injury in myocytes were examined. Freshly isolated adult canine myocytes were incubated with a superoxide generating (from dihydroxyfumarate) and Fe-catalyzed free radical system. Exposure of the myocytes to free radicals for 20 min resulted in more than a 5-fold increase in thiobarbituric acid reactant (peroxide) formation and elevated levels of lactate dehydrogenase (LDH) activity released into the media compared to controls. Ultrastructurally, severe sarcolemmal damage, mitochondrial and myofibril derangements were evident. At 40 min, cellular viability (trypan blue exclusion) in the samples exposed to free radicals decreased to about one-third of controls; concomitantly, major losses in total cellular phospholipids occurred. When the cells were pretreated with 200 microM propranolol before the addition of free radicals, both peroxide formation and increased LDH release were inhibited; in agreement, complete ultrastructural preservation was observed. In addition, the subsequent losses in cellular viability and phospholipids were prevented. For comparison, the more water soluble beta-blocker, atenolol at 200 microM was shown ineffective in providing significant protection against the induced injury. The results suggest that propranolol may provide antiperoxidative protection to myocytes when elevated levels of free radicals are present. PMID- 2231737 TI - Effects of hypoxia, acidosis, and simulated ischemia on repriming of caffeine contracture in rat myocardium. AB - This study was designed to examine the effects of hypoxia, acidosis, glucose-free medium and their combination on contraction and sarcoplasmic reticulum (SR) function in rat ventricular trabeculae. The isometric twitch tension was measured during superfusion with hypoxic (PO2 less than 30 mmHg), acidic (pH 6.80), glucose-free, or their combined ("ischemic") Tyrode's solution at 20 degrees C. The time needed to fully recover the contraction induced by 10 mM caffeine (repriming time) was measured to indirectly estimate the Ca2+ uptake of the SR. In "ischemia" and acidosis, the peak developed tension decreased progressively for the first 30 min (37.6 +/- 9.2% and 56.6 +/- 8.4% of control at 30 min, respectively), and then became steady. In hypoxic solution, the peak developed tension decreased moderately for the first 30 min (86.8 +/- 4.8% of control at 30 min), and thereafter remained steady. Developed tension did not change significantly during 60 min of superfusion with glucose-free solution. The repriming time of caffeine contraction was significantly delayed in both "ischemic" and hypoxic solutions, but was unchanged in acidic and glucose-free solutions. These results lead us to suggest that depressed SR function to accumulate Ca2+ may contribute to the decline in tension in ischemia and hypoxia, but that other mechanisms are important in the tension decline induced by acidosis. PMID- 2231738 TI - Regulation of systolic force and control of free energy of ATP-hydrolysis in hypoxic hearts. AB - In isolated isometrically working rat hearts during graded, constant pressure hypoxic saline perfusion (PO2 140-700 mmHg) heart rate was changed experimentally between 80 and 400/min. The following parameters were recorded or estimated: peak systolic pressure, dP/dtmax, dP/tmin, oxygen consumption (VO2), venous PO2, ATP, ADP, phosphocreatine, creatine and inorganic P. Free energy of ATP hydrolysis (dG/d xi) was calculated from cytosolic concentration using CK-equilibrium equation. Two predominant responses of the hearts to hypoxia were observed, pronounced negative force frequency relationship; maintained energetic state (Free energy, dG/d xi) at the respective level of hypoxia if contractile force and beating rate were varied by a factor of 4-5. The enhanced force frequency relationship with a maintained free energy level is interpreted in terms of downregulation of EC-coupling (including duration of action potential) which comprises a possible cardioprotective effect. PMID- 2231739 TI - Functional interconversion of rest decay and ryanodine effects in rabbit and rat ventricle depends on Na/Ca exchange. AB - Rapid cooling contractures were used to assess changes in sarcoplasmic reticulum (SR) Ca content in isolated rabbit and rat ventricular muscle during rest, with altered transsarcolemmal [Na] and [Ca] gradients and in the presence and absence of 100 nM ryanodine. In rabbit there is normally a rest-duration dependent decline in SR Ca content (rest decay), whereas in rat there is a short-term increase in SR Ca content (rest potentiation) and little evidence of rest decay. Ryanodine greatly accelerates the rate of rest decay in rabbit, depleting the SR of Ca in approximately 1 s, whereas in rat, ryanodine does not appear to drain the SR even after a 10 min rest. Elevation of intracellular Na activity in rabbit (by Na-pump inhibition) to a level similar to that measured in control rat during rest (Shattock and Bers, Am. F. Physiol., 256: C813-C822, 1989) makes rest dependent changes of SR Ca content in these two tissues similar. The rest decay in rabbit in the presence of ryanodine is also markedly slowed after Na-pump inhibition. In rat, reduction of [Ca]0 allows rest decay to occur (+/- ryanodine), but this rest decay can be largely prevented by simultaneous reduction of [Na]o (to maintain [Na]3/[ Ca] constant) which serves to keep the thermodynamic driving force on a 3:1 Na/Ca exchange constant. We conclude that the process of rest decay and rest potentiation in both rabbit and rat ventricle depends on the sarcolemmal Na/Ca exchange. Furthermore, these species can be functionally interconverted by manipulation of the [Na] and [Ca] gradients. The ability of ryanodine to deplete the SR of Ca also depends critically on other transport systems (particularly Na/Ca exchange) to remove Ca from the cytoplasm. PMID- 2231740 TI - Protein kinase C activation enhances the delayed rectifier potassium current in guinea-pig heart cells. AB - The possible involvement of protein kinase C in modulating membrane currents was investigated in isolated guinea-pig ventricular cells. In a Na(+)-and K(+)-free external solution, the delayed rectifier K+ current (IK) was increased by the activator of protein kinase C (PKC), 12-O-tetradecanoylphorbol-13-acetate (TPA). The amplitude of the IK tail elicited by a return from a depolarizing pulse for 3 s at + 50 mV to a holding potential of -30 mV was increased by 32 +/- 4% (mean +/ S.E., (n = 6) after the external application of 1 nM TPA, and by 60 +/- 17% (n = 5) after 10 nM. The increase in IK produced by 1 nM TPA was abolished by the inhibitor of PKC, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7, 10 microM). In addition, the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol (OAG, 125 microM) also increased IK (58 +/- 9%, n = 3). PKC purified from bovine brain remarkably increased IK (151 +/- 101%, n = 5) in the presence of 1 nM TPA when it was internally applied using the cell dialysis method. The concentration-response curve of IK for the intracellular concentration of Ca2+ was shifted to the left by 1 nM TPA, suggesting a Ca2(+)-dependent action of PKC and/or altered Ca2(+) sensitivity of IK channels by phosphorylation. On the other hand, 1 nM TPA had no substantial influence on the Ca2+ current (decreased by 7 +/- 4%, n = 5) or the inward-rectifier K+ current (decreased by 5 +/- 5% in outward component, and 3 +/ 8% in inward component, n = 6). Therefore, the action of PKC was to specifically increase IK without affecting the other two currents. PMID- 2231741 TI - Israeli Group for Heart Research (IGHR). Abstracts presented at the VIth annual meeting. April 26, 1990, Tel Aviv, Israel. PMID- 2231742 TI - Angiotensin II: hemodynamic regulator or growth factor? AB - The evolution of our understanding of the actions of ANG II can be described in terms of 3 paradigms that also characterize the development of our knowledge of cardiovascular regulation. The first paradigm, organ physiology, described the variable performance of the heart in terms of length-dependent changes in myocardial contractile function (Starling's Law), and Ang II as a pressor factor that elevated blood pressure. With the shift to the second paradigm, cell biochemistry and biophysics, regulation of cardiac performance came to be explained by altered calcium fluxes and changing myocardial contractility, while the clinical effects of Ang II were understood in terms of changes in the calcium fluxes that control smooth muscle contraction. The third paradigm, gene expression (molecular biology), probably describes the most primitive--and complex--of these regulatory mechanisms. Altered gene expression in response to a variety of chemical and physical forces can explain several aspects of the long term regulation of cardiac performance in terms of adaptative changes in the architecture and composition of a heterogeneous population of myocardial cells. This third paradigm also describes important effects of Ang II to increase protein synthesis and promote cell growth that appear able both to ameliorate and exacerbate human disease. It is, therefore, probably inappropriate to view Ang II mainly as a vasoconstrictor with secondary effects to induce cell hypertrophy. Instead, Ang II may have been derived from a primitive growth factor that, because it utilized Ca2+ to mediate its effects on gene expression, later in evolution acquired the ability to increase smooth muscle tone and myocardial contractility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231743 TI - Spatial arrangements of microfibrils in myocardial scars: application of antibody to fibrillin. AB - Acute myocardial infarction kills myocytes; viable and necrotic myocytes disconnect and the ends of the viable cells become anchored to collagen fibers during reparative scar tissue formation. These anchorages have not been examined in detail, although previous studies have shown that microfibrils (MFs) concentrate at the edges of scars and at the tips of normal papillary muscles. We examined the spatial arrangements of MFs at these two sites in human hearts. Light and electron microscopic observations were made on tissue samples oriented in the long axis of myocytes and stained with monoclonal antibodies to fibrillin, a glycoprotein component of human microfibrils. MFs had identical arrangements at both sites, where they formed fibrous connections between myofibers and collagen fibers. These connections were oriented in the long axis of the muscle cells. At the myocyte ends, MFs appeared to intertwine with MFs in the normal endomysium; in the main body of the connections, MFs formed compact, 200 to 500 nm thick, fibrillin-positive fibers; and at the collagen ends, MFs splayed out among collagen fibrils. These observations indicate that MFs form myofiber-collagen fiber linkages at sites where the power of myocardial contraction is being transmitted to the extracellular connective tissue framework. Formation of such linkages seems to be an important step in the successful repair of necrotic myocardial lesions. PMID- 2231744 TI - Protective effect of verapamil in ischemic porcine hearts: analysis of ultrastructural and metabolic changes using in vivo 31P-NMR spectroscopy. AB - To assess the protective effect of verapamil on ischemic myocardium, the changes in high energy phosphates, inorganic phosphate, and intracellular pH were serially and quantitatively measured in ischemic porcine hearts without collateral circulation using 31P-NMR spectroscopy, together with ultrastructural examination. Twenty-six farm pigs weighing 11 to 14 kg were anesthetized with fluothane and were divided into control (C) group and verapamil pretreatment (V) group. In V group 0.2 mg/kg of verapamil was administered for 20 mins before occlusion of the anterior descending coronary artery. 31P-NMR spectra were serially obtained throughout the experiment, and ultrastructural examination was done at 20-min occlusion and at 120-minute occlusion in each group. At 10-min ischemia, creatine phosphate was significantly preserved in V group (C/V = 11 +/- 4%/16 +/- 5% P less than 0.05). At 20 min ischemia, ATP was significantly preserved (C/V = 60 +/- 9%/73 +/- 8% P less than 0.05), and intracellular pH was significantly higher in V group (C/V = 6.4 +/- 0.2/6.6 +/- 0.1 P less than 0.05). Morphologically, clumping of the nuclear chromatin, mitochondrial swelling and decrease in glycogen were milder in V group at 20 min ischemia. However, these beneficial effects disappeared at 120 min ischemia. Thus pretreatment with verapamil attenuated depletion of high energy phosphates, progression of acidosis, and ultrastructural changes. There was no significant difference of rate pressure product and regional blood flow between hearts with and without pretreatment of verapamil. Therefore, this protective effect may be due to the energy sparing effect or other direct subcellular effect of verapamil on ischemic myocyte. PMID- 2231745 TI - The cell surface of isolated cardiac myocytes--a light microscope study with use of fluorochrome-coupled lectins. AB - In cells isolated from guinea-pig or rat ventricular muscle occurrence and distribution of carbohydrate components of the surface coat were monitored using fluorochrome-coupled lectins. Fluorescence of membrane-bound lectins was assayed by an image analysis system. The lectins ConA, WGA, sWGA, LFA and RCA-I showed specific binding to the whole myocyte surface, indicating a homogeneous distribution of alpha-mannosyl, alpha-glycosyl, N-acetylglucosaminyl, N acetylneuraminate and beta-galactosyl residues. Binding of DBA and SBA, with specific affinity for N-acetylgalactosaminyl residues, to guinea-pig cardiac myocytes was mainly at the cell poles corresponding to intercalated discs in intact tissue. Both lectins failed to interact with rat myocytes. UEA-I, specific for alpha-L-fucose, bound slightly to rat and not to guinea-pig myocytes. Binding of PNA to guinea-pig myocytes was observed only after cleaving off sialic acids from cell surface, suggesting that sialic acids mask galactosyl-beta(1,3)-N acetylgalactosamine residues. Specificity of lectin-cell interaction was tested by an inhibition assay where free sugars were tested for their capacity to inhibit lectin binding to the myocytes. When comparing different isolation procedures based on different proteolytic enzymes, the myocytes' affinity to any lectin was found to be qualitatively unchanged. Investigation of lectin-decorated myocytes by means of confocal laser scan microscopy showed that lectin binding sites are not confined to the cell surface but are also present in sarcolemmal invaginations, i.e. transverse tubules. This suggests that the tubular system is lined with a carbohydrate layer similar to, and continuous with, that of the peripheral cell surface. PMID- 2231746 TI - Purine release from isolated rat heart: a new approach to the study of energy metabolism. AB - The rate of release of purines (adenosine, inosine, hypoxanthine, xanthine and uric acid) from isolated working rat hearts was measured and compared to tissue concentrations of high energy phosphate compounds. Hearts were subjected to different workloads, and perfusions were performed: with normal oxygen supply (group 1); with the addition of insulin to the standard perfusion buffer, which contained glucose as energy source (group 2); in hypoxic conditions (group 3). In each group purine release increased (P less than 0.01) at higher workload and was closely related to indices of mechanical performance such as cardiac output or minute work (r = 0.902 and 0.858 in group 1, r = 0.902 and 0.851 in group 2, r = 0.851 and 0.881 in group 3, P less than 0.001 in each case). Work had no effect on adenine nucleotides but produced a significant (P less than 0.01) reduction in phosphocreatine/creatine ratio. The comparison of different groups showed that at any level of heart performance purine release was higher (P less than 0.001) in group 3 vs. group 1, and lower (P less than 0.001) in group 2 vs. group 1. High energy phosphates were reduced in group 3 vs. group 1 but were unchanged in group 2 vs. group 1. We conclude that in the isolated heart purine release is directly related to the rate of energy consumption, and inversely related to the rate of energy production. Purine release provides a sensitive method to evaluate myocardial energy metabolism, which is more sensitive than measurement of high energy phosphates. PMID- 2231747 TI - Subcellular distribution of myocardial 5'-nucleotidase. AB - The controversial subject of the subcellular location of myocardial adenosine production was studied employing density gradient fractionation of heart muscle combined with a novel method for analyzing distribution profiles based on multiple regression (correlation) analysis. Bungarotoxin binding, N-acetyl-beta-D glucosaminidase, cytochrome c oxidase, NADPH-dependent cytochrome c reductase and lactate dehydrogenase were used as markers for the plasma membrane, lysosomes, mitochondria, sarcoplasmic reticulum and cytosol, respectively. The normalized distribution frequencies (fraction of total) of 5'-nucleotidase in mitochondria, lysosomes, plasma membranes, sarcoplasmic reticulum and cytosol in the 50 x g supernatant of total homogenate of heart muscle were found to be 0, 0.25, 0.44, 0.08 and 0.23, respectively. To increase the resolution power of this approach with respect to mitochondria, a crude mitochondrial fraction was also studied, in which the normalized distribution of 5'-nucleotidase in the homogenate was 0, 0.16 and 0.84 in mitochondria, plasma membranes and lysosomes, respectively. This mainly lysosomal 5'-nucleotidase activity was 61% inhibited by the alpha,beta methylene analog of ADP, indicating that although the latter has been considered specific to the plasma membrane enzyme, it also inhibits the lysosomal enzyme. The intercellular distribution of 5'-nucleotidase was not studied, but the lack of this enzyme in the mitochondria indicate that the adenosine production observed during mitochondrial AMP production, e.g. during acetate oxidation in intact heart muscle, must involve AMP transport out from the mitochondria. PMID- 2231748 TI - Are reperfusion-induced arrhythmias caused by disinhibition of an arrhythmogenic component of ischemia? AB - Isolated rat hearts were used to examine whether reperfusion-induced arrhythmias may be caused by washout of substances accumulating during ischemia. This was achieved by subjecting hearts to 10 min of regional ischemia and rendering them transiently inexcitable during the first 1.5 min of reperfusion. Transient inexcitability was induced by switching to cold solution (4 degrees C) shortly before reperfusion (-1.5 min). In controls (no hypothermia), the incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF) were 83% and 92%, respectively, during the first 1.5 min of reperfusion. Transient hypothermia caused inexcitability and asystole, impaired recovery of coronary flow and abolished VT and VF (all P less than 0.05). On subsequent rewarming to 37 degrees C, coronary flow and sinus rate recovered in all hearts. However, VT and VF occurred in only 58% and 25%, respectively (P less than 0.05). These values were similar to those of new episodes of VT and VF occurring in controls during the equivalent period. Therefore arrhythmias had been abolished during transient hypothermia, not merely delayed. The relative contributions of transient impairment of recovery of coronary flow and transient asystole to the antiarrhythmic effects were examined in a further 10 groups of hearts (n = 12/group) in which reperfusion conditions were transiently manipulated. We utilized combinations of hypothermia, ventricular pacing, acetylcholine (ACh) 55 microM (to cause asystole and impairment of recovery of coronary flow), and right atrial excision and left atrial pacing (to permit bradycardia to be transiently induced during reperfusion by temporarily switching off the pacemaker). The results indicated that transient hypothermia was antiarrhythmic as a result of a reduction of excitability, not because of bradycardia or impairment of recovery of flow. The data support the hypothesis that reperfusion unmasks (disinhibits) latent arrhythmogenic components of ischemia (particularly during the first 1.5 min of reperfusion) and that, by inducing inexcitability, transient hypothermia allows these substances to be washed out without their arrhythmogenic effects being manifested. The identities of the arrhythmogenic and antiarrhythmic substances remain to be determined; we suggest that cyclic AMP and potassium, respectively, are likely candidates. PMID- 2231749 TI - Effect of 2,3-butanedione 2-monoxime on slow inward and transient outward currents in rat ventricular myocytes. AB - The effect of 2,3-butanedione 2-monoxime (BDM), a substance possessing phosphatase-like activity, was studied on action potentials of isolated rat heart and on the slow inward calcium current and outward current (including the 4 aminopyridine (4-AP)-sensitive transient outward component), in rat ventricular myocytes. In contrast to what was observed by other authors in different species and cardiac tissues, BDM increased markedly the amplitude and duration of the rat ventricular action potential plateau. On the other hand, in the presence of 4-AP and ryanodine BDM shortened action potential duration. BDM decreased in a dose dependent manner the amplitude of both the slow inward calcium current and the transient outward current, accelerated their inactivation and shifted their steady-state inactivation-voltage relationships towards negative potentials. BDM also depressed other components of outward current. It is suggested that the lengthening effect of BDM on action potential duration results mainly from the simultaneous reduction of both the slow inward calcium current and the transient outward current, two antagonistic currents with unequal influences on action potential plateau development. The similarity of effect of BDM on these two currents also suggests that ionic channels generating them might require similar phosphorylation for their functioning. PMID- 2231751 TI - Scientists closer to using alpha-particle-emitting isotopes as cancer treatment. PMID- 2231750 TI - Implications of potential positive correlation between autologous tumor-cell killing activity and prognosis in lung cancer. PMID- 2231752 TI - OTA report disputes success of unconventional cancer therapies. PMID- 2231753 TI - NCI awards Jackson Lab $9.5 million to rebuild. PMID- 2231754 TI - Bone marrow transplant pioneer wins Nobel. PMID- 2231755 TI - Race, nutritional status, and survival from breast cancer. AB - The effects of nutritional status on differences in the survival of black and white women with breast cancer were studied in a cohort of 1,960 Georgia women diagnosed during 1975-1979. After data were adjusted for stage of disease, socioeconomic status, and other prognostic factors, poorer survival rates were shown in black women. Within each stage classification, lower levels of serum albumin and hemoglobin and higher relative body weight were more common among blacks and were independently associated with poorer survival. Among women with stage 3 disease, adjustment for these variables substantially reduced the excess mortality rate among blacks, suggesting that racial differences in survival may be partly explained by differences in nutritional status or extent of disease within stage. PMID- 2231756 TI - Effect of tamoxifen on serum insulinlike growth factor I levels in stage I breast cancer patients. AB - Insulinlike growth factor I (IGF-I) has been shown to be a potent mitogen for breast cancer cells in vitro, and IGF-I receptors have been demonstrated on human primary breast neoplasms. In a randomized, placebo-controlled study, we document that administration of the antiestrogen tamoxifen to patients with breast cancer was associated with a statistically significant (P = .002) reduction in the serum level of IGF-I. The mean IGF-I level was 1.4 U/mL in the placebo-treated group and 0.9 U/mL in the tamoxifen-treated group. Because serum IGF-I level is growth hormone (GH) dependent and because data suggest that the pubertal surge in GH and IGF-I levels is sex steroid dependent, we speculate that the mechanism underlying our observation may involve blockade by tamoxifen of estrogen action in the hypothalamic-pituitary axis. We conclude that tamoxifen treatment reduces IGF-I levels and that this reduction may contribute to the therapeutic effect of the drug. PMID- 2231757 TI - Prediction of postoperative clinical course by autologous tumor-killing activity in lung cancer patients. AB - Fifty patients with primary localized lung cancer were tested at the time of surgery for the ability of their lymphocytes to kill autologous, freshly isolated tumor cells, and the assay was evaluated for prognostic significance. Peripheral blood lymphocytes of 27 patients (54%) demonstrated significant autologous tumor killing activity in 6-hour 51Cr-release assays. Twenty-three of the 27 patients with autologous tumor-killing activity remained tumor free and survived more than 5 years after curative surgery, while all 23 who were negative for autologous tumor-killing activity relapsed by 18 months after surgery and died within 42 months after surgery. The differences in survival curves for the two groups were highly significant (P less than .00003). Autologous tumor-killing activity was not correlated with natural killer (NK) cell activity against K562 human myeloid leukemia cells or proliferation of lymphocytes stimulated with autologous, freshly isolated tumor cells in mixed culture. There were no differences in total survival between patients with positive results and those with negative results in tests of NK cell activity and autologous mixed lymphocyte-tumor culture reaction. These results indicate that autologous tumor-killing activity is a meaningful prognostic indicator and provide evidence for immunological control of tumor growth and metastasis. According to our preliminary data, it is unlikely that lung cancer patients who remain tumor free after 60 months of follow-up will develop recurrence or die from the disease. We are conducting a study to determine whether induction of autologous tumor-killing activity before surgery, by treatment with biological response modifiers,can improve the clinical outcome in patients who do not naturally have this potential. PMID- 2231758 TI - Reduction of the membrane fluidity of human breast cancer cells by tamoxifen and 17 beta-estradiol. AB - The intracellular steady-state levels of methotrexate were previously shown to be reduced in estrogen receptor (ER)-negative human breast cancer MDA-MB-436 cells and ER-positive human breast cancer MCF7 cells following treatment with pharmacologically relevant concentrations of 17 beta-estradiol (E2). We now report that both E2 and tamoxifen (TMX) significantly decreased the fluidity of MCF7 and MDA-MB-436 cellular membranes. With E2 or TMX at concentrations greater than 1 microM, perturbations in membrane fluidity were accompanied by apparently non-ER-mediated cytotoxicity. Alterations in membrane structure may have contributed to the cytotoxicity of high-dose endocrine therapy and to the ability of E2 to inhibit methotrexate transport and cytotoxicity in some human breast cancer cells. PMID- 2231759 TI - Antitumor activity of liposome-encapsulated doxorubicin in advanced breast cancer: phase II study. AB - Previous studies in animals have demonstrated liposome-encapsulated doxorubicin (LED) has substantially less cardiac toxicity than free doxorubicin but retains antitumor activity. In a phase I clinical study of LED, the maximum tolerated dose was 90 mg/m2 and dose-limiting toxicity was considered to have been reached when granulocytopenia was produced. We used LED to treat 20 patients with advanced, measurable breast cancer. LED was given at doses of 60-75 mg/m2 every 3 weeks as an intravenous infusion. Regression of disease was objectively measured in nine patients; in five of these patients, complete regression of the index lesion occurred. The mean duration of the responses was 7 months. Hematologic toxicity consisted of grade 1-2 leukopenia in some patients. Gastrointestinal toxicity and mucositis were generally mild and tolerable. Alopecia occurred in all patients and usually was complete. Twelve patients received cumulative doses of LED of greater than 400 mg/m2 and were evaluated with radionuclide ventriculograms. In eight patients, the cumulative dose was greater than 500 mg/m2, and five had endomyocardial biopsies. Four of these biopsy results were Billingham grade 0, while one (cumulative LED dose, 750 mg/m2) showed grade 1 changes with mild myofibrillar loss and dilatation of the sarcoplasmic reticulum involving less than 5% of cardiac myocytes. Two patients had decreases in left ventricular ejection fraction. One of these patients had received a total dose of LED of 630 mg/m2 and had a decline of 13% in left ventricular ejection fraction, but had no clinical evidence of congestive heart failure and had a Billingham grade 0 endomyocardial biopsy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231760 TI - Oral zidovudine, continuous-infusion fluorouracil, and oral leucovorin calcium: a phase I study. AB - A phase I clinical, pharmacologic, and biochemical evaluation of escalating oral zidovudine (AZT) given over 2 days with a fixed dose of continuous-infusion fluorouracil (800 mg/m2 per day X 3 days) and oral leucovorin calcium was performed. Eighteen patients were treated with doses of AZT ranging from 1.0 to 9.0 g/m2 per day. Nausea and vomiting were dose limiting, with a maximally tolerated dose of 7.5 g/m2 per day. Rash and mucositis occurred but were not dose limiting. A dose-related increase in peak plasma levels of AZT was observed, and the alpha half-life of AZT in plasma (75 min) was unaffected by these high doses. At doses above 4.0 g/m2 per day, trough levels significantly increased, perhaps reflecting prolonged absorption from the gut. No responses were observed; however, a significant increase in DNA single-strand breaks was observed in peripheral blood cells after a threshold dose of 4.0 g/m2 per day, confirming a biological effect of AZT in this regimen. Further trials with an intravenous formulation capable of maintaining plasma levels and circumventing dose-limiting toxicity are warranted. PMID- 2231761 TI - Language preference as an indicator of mammography use among Hispanic women. PMID- 2231762 TI - Indoor radon and lung cancer in China. PMID- 2231763 TI - Staurosporine: a prototype of a novel class of inhibitors of tumor cell invasion? PMID- 2231764 TI - Low-fat diet trial set to take off. PMID- 2231765 TI - Prevention trial with tamoxifen being considered. PMID- 2231766 TI - 1991 appropriations for cancer research approved by Senate. PMID- 2231767 TI - False screening claims undermine breast cancer detection efforts. PMID- 2231768 TI - Guidelines set for early release of clinical data. PMID- 2231769 TI - Validation of intermediate end points in cancer research. AB - Investigations using intermediate end points as cancer surrogates are quicker, smaller, and less expensive than studies that use malignancy as the end point. We present a strategy for determining whether a given biomarker is a valid intermediate end point between an exposure and incidence of cancer. Candidate intermediate end points may be selected from case series, ecologic studies, and animal experiments. Prospective cohort and sometimes case-control studies may be used to quantify the intermediate end point-cancer association. The most appropriate measure of this association is the attributable proportion. The intermediate end point is a valid cancer surrogate if the attributable proportion is close to 1.0, but not if it is close to 0. Usually, the attributable proportion is close to neither 1.0 nor 0; in this case, valid surrogacy requires that the intermediate end point mediate an established exposure-cancer relation. This would in turn imply that the exposure effect would vanish if adjusted for the intermediate end point. We discuss the relative advantages of intervention and observational studies for the validation of intermediate end points. This validation strategy also may be applied to intermediate end points for adverse reproductive outcomes and chronic diseases other than cancer. PMID- 2231770 TI - Inhibition of invasion of invasive human bladder carcinoma cells by protein kinase C inhibitor staurosporine. AB - To study the effect of the protein kinase C (PKC) inhibitor staurosporine on invasion, we selected the invasive human bladder carcinoma cell line EJ. Total PKC activity was more than twofold higher in the EJ cells than in RT4 cells (superficial human bladder carcinoma cells), which do not pass through an artificial basement membrane. There was more PKC activity in the cytosol than in the membrane of EJ cells. Staurosporine, at nontoxic concentrations, inhibited the invasion of EJ cells through an artificial basement membrane in a dose dependent manner. Staurosporine caused a dose-dependent inhibition of cell motility but did not inhibit cell attachment. Staurosporine represents a new agent for the inhibition of tumor cell invasion and may prove useful in studying the mechanisms responsible for this phenomenon. PMID- 2231771 TI - Feasibility of cellular microencapsulation technology for evaluation of anti human immunodeficiency virus drugs in vivo. AB - We investigated the feasibility of micro-encapsulation technology for the evaluation of anti-human immunodeficiency virus (HIV) drugs in vivo. The ability to place human cells in microcapsules with semipermeable membranes for implantation into test animals led to the development of this assay. The anti-HIV activity assay involves microencapsulating human T-lymphoblastoid cells sensitive to the cytopathic effects of HIV; the encapsulated cells are then implanted into athymic nude mice and recovered after drug treatment in vivo. A positive antiviral effect of the test substance is indicated by growth or survival of the virus-infected cells in the microcapsules. Several HIV-sensitive cell lines of T lymphocyte, monocyte, and nonlymphocyte origin were examined for growth in microcapsules in vitro and in vivo. Light and electron microscopic analysis of the capsules and the human cells contained therein revealed the invasion of mouse immune cells and other adverse effects that could not be overcome by any of numerous technical modifications attempted. We conclude that cellular microencapsulation technology is not feasible for in vivo drug-testing protocols because of immunogenic reactions. PMID- 2231772 TI - Nonrandom chromosomal abnormalities in primary uveal melanoma. AB - We report on 14 cases of clonal chromosomal anomalies in patients with primary uveal melanoma. An increased dosage of chromosome 8 or of parts of the long arm of chromosome 8 (8q) were detected in eight patients (57%). The smallest multiplied area of 8q appeared to be the region 8q2.1----qter. Monosomy of chromosome 3 was seen in six patients (43%), five of which were associated with anomalies of chromosome 8. Increased dosage of parts of chromosome 8q and loss of heterozygosity of chromosome 3, or the combination of both, seemed to be nonrandom for uveal melanoma and may distinguish it genetically from cutaneous malignant melanoma. Anomalies of chromosome 6, mostly resulting in additional material of 6p or a deletion of 6q, were found in six patients (43%). These anomalies, which seem to be common features of cutaneous malignant melanoma, were considered secondary rather than primary changes in uveal melanoma, since they were present only in subclones in most cases. Loss of the Y chromosome, restricted to tumor cells, was detected in four male patients, and loss of one X chromosome was detected in a female patient. PMID- 2231773 TI - Prospective study of the frequency and size distribution of polyps missed by colonoscopy. AB - An important determinant in interpreting the results of colorectal polyp chemoprevention trials is the rate of polyps missed during colonscopic examination. We prospectively examined 90 patients by tandem colonoscopy performed by two alternating examiners. In 69 (76.7%) patients, 221 neoplastic lesions were documented histologically. Of a total of 58 lesions detected in 31 patients, no neoplastic lesion greater than or equal to 10 mm in size was missed; 16% of diminutive (less than or equal to 5 mm) neoplastic polyps and 12.3% of medium-sized (6-9 mm) neoplastic polyps were missed by the first examiner. We conclude that an experienced colonoscopist will miss about 15% of colorectal neoplastic polyps less than 10 mm in size in the setting of adequate bowel preparation. Large (greater than or equal to 10 mm) polyps were rarely missed, however, with the "miss" rate in our study equal to 0, with a 95% confidence limit of 4.64%. PMID- 2231774 TI - Phase II investigation of pentostatin in multiple myeloma: a Southwest Oncology Group study. PMID- 2231775 TI - Potential misclassification in some studies claiming an association between chlorophenol exposure and various malignancies. PMID- 2231776 TI - Neurotoxicity and carcinogenicity of N-methylolacrylamide in F344 rats and B6C3F1 mice. AB - Toxicology and carcinogenicity studies of N-methylolacrylamide were conducted by administering the chemical by gavage in water to both sexes of F344/N rats and B6C3F1 mice 5 times per week for 16 d, 13 wk, or 2 yr. In 16-d studies, rats receiving doses of 200 mg/kg or higher and mice receiving 400 mg/kg died. In 13 wk studies, all rats given 100 mg/kg or higher doses died. Rats receiving 50 mg/kg or higher doses developed hindlimb ataxia progressing to paralysis. In neurobehavioral assessments, decreased forelimb and hindlimb grip strength occurred in rats at doses as low as 12.5 mg/kg. Landing footspread was also increased in dosed rats compared to controls. Axon filament and myelin sheath degeneration in the spinal cord and/or peripheral nerves occurred in rats receiving doses of 25 mg/kg or higher. Necrosis in the granular cell layer of the cerebellum was seen in rats given 200 mg/kg. Mice receiving 200 mg/kg in 13-wk studies died. Decreased grip strength was noted in mice at doses as low as 25 mg/kg, and rotarod performance was also affected by N-methylolacrylamide administration, but no neuropathology was seen microscopically. Testicular weights were decreased at doses as low as 12.5 mg/kg, and hepatocellular necrosis, thymic lymphocyte necrosis, and hemorrhage, necrosis, and mineralization of the zona reticularis of the adrenal gland were seen in mice that died (200 mg/kg). In 2-yr studies, survival and weight gains in male and female rats receiving doses of 6 or 12 mg/kg/d were minimally affected. No biologically important clinical signs or neoplastic or nonneoplastic lesions were attributed to N-methylolacrylamide administration to rats, suggesting that higher doses could have been tolerated. In mice, survival was not different between dosed and control groups (0, 25, or 50 mg/kg/d). Body weights were higher by as much as 25% in dosed compared to control groups. No compound-related clinical signs were observed, but increases in neoplasms of the harderian gland, liver, and lung were clearly related to chemical administration in both sexes of mice. Benign granulosa-cell neoplasms of the ovary were also increased in dosed female mice. PMID- 2231777 TI - Metabolism of 1-nitropyrene by human, rat, and mouse intestinal flora: mutagenicity of isolated metabolites by direct analysis of HPLC fractions with a microsuspension reverse mutation assay. AB - The metabolism of [14C]-1-nitropyrene by human, rat and mouse intestinal microflora and a bioassay-directed chemical analysis of the isolated metabolites by assaying HPLC fractions with a microsuspension reverse mutation assay were examined. [14C]-1-Nitropyrene was metabolized by human, rat, and mouse intestinal microflora to 1-aminopyrene, N-acetyl-1-aminopyrene, N-formyl-1-aminopyrene, and two unknown metabolites identified as A and B. The predominant metabolite produced by human, rat, or mouse intestinal microflora following a 12-h incubation with [14C]-1-nitropyrene was 1-aminopyrene, which accounted for 93, 79, and 88% of the total 14C, respectively. Only minor amounts of N-formyl-1 aminopyrene (1.4, 1.2, and 1.0%), N-acetyl-1-aminopyrene (4.4, 3.0, and 3.4%), unknown A (1.0, 1.2, and 1.0%), and unknown B (3.3, 5.0, and 1.2%) were detected. These data suggest that a similar mechanism exists in the biotransformation of 1 nitropyrene by intestinal microflora from all three sources. Direct mutagenicity analysis of the HPLC fractions produced by intestinal microflora with the microsuspension reverse mutation assay indicated that mutagenic fractions can be resolved using this methodology. PMID- 2231778 TI - Morphometric analysis of osteosclerotic bone resulting from hexachlorobenzene exposure. AB - Hexachlorobenzene (HCB) exposure has been shown to induce hyperparathyroidism and osteosclerosis in rats. Experiments were undertaken to investigate the effects of HCB-induced hyperparathyroidism and osteosclerosis on femur morphometry as well as femur breaking strength. Fischer 344 rats were dosed 5 d/wk for 15 wk with 0, 0.1, 1, 10, or 25 mg HCB/kg body weight. Hyperparathyroidism was produced in the two higher dose groups as reported previously (Andrews et al., 1989). Femur weight was significantly increased in the rats receiving 0.1, 1, and 25 mg HCB/kg body weight, whereas density was increased significantly at 1, 10, and 25 mg HCB/kg dose levels. Bone strength was also significantly increased at the three higher dose levels. Cross-sectional area of the midpoint of the femur was significantly increased at the 1 mg/kg HCB dose level. Cortical area and the proportion of the total area of the bone that the cortex occupied were significantly increased at the three higher dose levels. Medullary cavity area was significantly increased at the 0.1 mg/kg dose level but significantly decreased at the 2 higher dose levels of HCB. The right femur was significantly predominant to the left femur in weight, volume, and density through all dosing regimens. HCB exposure significantly altered bone morphometry and strength characteristics in the Fischer 344 rat. PMID- 2231779 TI - Chlorinated aliphatic hydrocarbons promote lipid peroxidation in vascular cells. AB - Chlorinated aliphatic hydrocarbons such as trichloroethylene and trichloroethane cause acute and chronic cardiotoxicities via mechanisms that are still obscure. Some of these toxic effects may result from free-radical-induced membrane damage to the vascular tissues. The pro-oxidant effects of carbon tetrachloride, trichloroethylene, 1,1,1-trichloroethane, 1,2-dichloroethane, and trans-1,2 dichloroethylene were assessed in cultured arterial endothelial and aortic smooth muscle cells. Exposure of the cells to the above chemicals alone did not increase the formation of thiobarbiturate reactive products above background levels. However, in the presence of low levels of iron (3.1-25 microM Fe3+ chelated by ADP), all five agents promoted lipid peroxidation up to 200% of control. The rank order of potency is carbon tetrachloride greater than or equal to trichloroethylene greater than 1,1,1-trichloroethane greater than trans-1,2 dichloroethylene greater than 1,2-dichloroethane. The synergistic interaction between iron and chlorinated hydrocarbons in promoting lipid peroxidation may contribute to the cardiotoxicities of these agents. PMID- 2231780 TI - Failure of benzene and phenol to serve as substrates for the peroxidatic action of catalase. AB - Evidence from several reports in the literature indicates a possible role for catalase in the metabolism of benzene. To investigate possible peroxidatic activity of catalase on benzene or its major metabolite, phenol, we employed an in vitro assay system that had been used previously to study the peroxidation of ethanol by catalase. Under conditions identical to those used to demonstrate catalase-mediated ethanol peroxidation we observed no peroxidase activity of catalase toward either benzene or phenol. We conclude that catalase is not involved in benzene metabolism and make the observation that, to date, no aromatic compounds have been demonstrated to be substrates for the peroxidatic mode of action of catalase. PMID- 2231781 TI - Subtractive cDNA cloning of RC3, a rodent cortex-enriched mRNA encoding a novel 78 residue protein. AB - A rodent cortex-enriched mRNA, RC3, was identified by screening a rat brain cDNA library with a cortex-minus-cerebellum subtracted cDNA probe. Conceptual translation of RC3 cDNA sequences indicates that the rat and mouse mRNAs encode identical, novel 78 amino acid proteins. The RC3 protein amino terminus contains a cysteine-rich domain similar to those found in snake venom neurotoxins; the carboxyl terminus contains a collagen-like motif that may function in the assembly of RC3 subunits into a multimeric protein. Western blot experiments with an antiserum to a synthetic peptide corresponding to 27 residues of the 78 residue sequence identify an immunoreactive polypeptide with 18 kDa gel mobility that is likely to correspond to the RC3 protein. Northern blot analysis and in situ hybridization experiments show that RC3 mRNA is highly enriched in rat brain, with restricted expression in neuronal subsets primarily in the cortex, striatum, and hippocampus as well as certain nuclei within the thalamus, hypothalamus, the olfactory bulb. PMID- 2231782 TI - GD3 ganglioside is prevalent in fully differentiated neurons from rat retina. AB - Adult mammalian retinas contain unusually high amounts of GD3, a ganglioside of the lactosylceramide series. In this respect, they differ from adult avian retina and other regions of the adult avian and mammalian brain, where GD3 is a minor ganglioside and gangliosides of the gangliotetraosylceramide series (GM1, GD1a, GD1b, GT1b) are the predominant ones. We compare here the ganglioside patterns of rat, human, horse, and guinea pig retinas, which are known to differ in the degree of vascularization and astrocytic cell content. All these retinas showed a prevalence of pathway "b" gangliosides over pathway "a" gangliosides but showed no correlation between GD3 content and the degree of vascularization and astrocytic cell content. Immunostaining of rat retina sections showed the presence of GD3 in the inner and outer plexiform layers and also in the ganglion cell and inner nuclear layers. About 60% of the cells dissociated from rat retina showed immuno-colocalization of GD3 and the neuronal marker class III beta tubulin isotype or cholera toxin binding. All morphologically identifiable glial Muller cells coexpress GD3 and gangliotetraosylgangliosides. GD3 was a minor ganglioside among these axonally transported by ganglion cells in rats and guinea pigs, suggesting that it is either not synthesized by ganglion cells or, if so, it is restricted to the cell soma and/or dendritic tree. Our results demonstrate that, unlike neurons from avian retina and other regions of avian and mammalian brain, neurons from mammalian retina not only contain gangliosides of the gangliotetraosylceramide series but also keep a prevalence of gangliosides of the lactosylceramide series (GD3) when they are fully differentiated. PMID- 2231784 TI - Protein synthesis in the neuropil of the rat dentate gyrus during synapse development. AB - Previous studies have shown that there are dramatic accumulations of polyribosomes under developing synapses on dendrites of CNS neurons. The present study was designed to evaluate what types of proteins might be synthesized by the synapse-associated polyribosomes. Hippocampal slices from rat pups sacrificed at 4, 7, 10, 12, 14, and 21 days after birth as well as slices from adult animals were incubated in a modified Eagle's medium containing 3H-leucine. After a 30 min exposure to radiolabeled amino acids, the slices were microdissected, separating the dendritic enriched molecular layer from the cell bodies of the dentate gyrus and the hippocampus proper. The level of protein synthetic activity was assessed by comparing the incorporation in cell body and dendritic laminae. Polypeptides present in each dissected zone were separated electrophoretically on 1D SDS polyacrylamide gels according to their molecular weight and the newly synthesized proteins were analyzed through gel fluorography. The overall level of 3H-amino acid incorporation into protein (measured as cpm/microgram protein) was higher than that of the adult at all postnatal ages. When the entire slice was analyzed, the maximum incorporation was at 12 days after birth. In the dissected subregions of the slice the peak protein synthetic activity in cell-body-enriched regions of dentate gyrus and hippocampus proper was at 4-7 days postnatal, declining between 7 and 21 days to values comparable to the adult. By contrast, protein synthesis in the molecular layer of the dentate gyrus did not peak until 12 days after birth, decreasing toward adult rates after 14 days. The overall pattern of Coomassie stained polypeptides present in the dentate molecular layer was comparable at all ages examined. Moreover, one-dimensional gel analysis showed no qualitative differences in the proteins that were synthesized in the three dissected zones across ages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231783 TI - Intracellular Na+ activity in cultured mouse oligodendrocytes. AB - Na(+)-selective double-barrelled microelectrodes were used to measure the intracellular Na+ activity (aiNa) and membrane potential (Em) in oligodendrocytes from cultures of embryonic mouse spinal cord. In Na(+)-free solutions aiNa rapidly fell from its baseline of about 15 mM to values below 1 mM. Elevation of the K+ concentration in the bath ([K+]o) from 5.4 to 15 or 50 mM elicited an aiNa decrease of 4.7 or 9.0 mM, respectively. Ouabain blocked the aiNa decrease in response to 50 mM K+ by 37%. Bath application of 1 mM glutamate resulted in a membrane depolarization of 4.5 mV and a concomitant rise of aiNa by 8.6 mM. aiNa increased by approximately 11 mM after washout of a solution containing 20 mM NH4+. This aiNa increase was not blocked by amiloride, excluding a major contribution of a Na+/H+ antiporter. We conclude that, in cultured oligodendrocytes, transmembraneous Na+ movements are involved in pH regulation, glutamate causes an influx of Na+, and that the Na+/K+ pump and passive KCl uptake contribute to K+ accumulation. PMID- 2231785 TI - Acute toxicity tests of mofezolac (N-22) in mice and rats. AB - Mofezolac (N-22) is a newly developed analgesic and anti-inflammatory agent. The acute toxicities of N-22 were investigated in ICR mice and Wistar rats in oral (p.o.), intraperitoneal (i.p.) and subcutaneous (s.c.) routes. LD50 values of N 22 in mice were 1528 mg/kg (p.o.), 275 mg/kg (i.p.) and 612 mg/kg (s.c.) for males, and 1740 mg/kg (p.o.), 321 mg/kg (i.p.) and 545 mg/kg (s.c.) for females. Those in rats were 920 mg/kg (p.o.), 378 mg/kg (i.p.) and 572 mg/kg (s.c.) for males, and 887 mg/kg (p.o.), 342 mg/kg (i.p.) and 510 mg/kg (s.c.) for females. The sex difference was not clearly observed in mice and rats, but the species difference was observed in p.o. routes. As an initial toxic sign, the hypoactivity was observed in mice and rats of all routes, subsequently, paleness of skin, anemic conjunctiva, emaciation, stupor and/or coma were observed in mice and rats of p.o. and i.p. routes. In rats of those routes, tonic and/or asphyxial convulsion and dyspnea were also observed. In pathological examination of mice and rats, gastrointestinal disorders were observed in p.o. and i.p. routes, and changes of subcutaneous tissue at the injection site were observed in s.c. route. PMID- 2231786 TI - [Three-month oral subacute toxicity study of mofezolac (N-22) in rats]. AB - A three-month oral subacute toxicity study of mofezolac (N-22), a non-steroidal anti-inflammatory agent, was performed using dose levels of 6, 20, 60 and 200 mg/kg in rats, and recovery was also assessed one month after withdrawal. 1. Toxic signs caused by N-22 administration, observed only in the 200 mg/kg group, were as follows: soiling around the mouth and/or nose, piloerection, anemia, diarrhea, emaciation and decreased spontaneous locomotor activity. Nine males and thirteen females in the 200 mg/kg group excreted bloody diarrhea and died of general exhaustion between weeks four and thirteen of study. 2. In the 200 mg/kg group, decrease in food consumption and suppression of body weight gain were noted in males from about week four and in females from about week six after initiation of administration, and increase in water consumption was noted in males from about week seven. 3. Urinary examination revealed a decline in urinary pH in males of the 20 mg/kg and above groups and elevation of urobilinogen levels in males of the 60 and 200 mg/kg groups. 4. Hematological examination showed decreases in erythrocyte count (RBC), hematocrit value (Ht) and hemoglobin concentration (Hb) and increase in reticulocyte rate in both sexes of the 200 mg/kg group and an increase in neutrophil rate in males of the 200 mg/kg group. 5. Biochemical examination demonstrated a decrease in chloride (Cl-) in males receiving the 20 mg/kg or above doses and a decrease in calcium (Ca++) in males of the 60 and 200 mg/kg groups. Moreover, there were decreases in cholinesterase (ChE) activity, total protein (TP) and albumin (Alb) values, as well as increases in blood urea nitrogen (BUN), uric acid (UA) and potassium (K+) in both sexes of the 200 mg/kg group, along with elevations in GOT and lactate dehydrogenase (LDH) activities in females of the 200 mg/kg group. 6. The absolute and/or relative organ weights for liver, kidneys, spleen and adrenals were increased in the 200 mg/kg group. 7. On pathological examination, perforating ulceration in the jejunum and ileum, turbid ascites, adhesion and inflammatory changes in capsules of the abdominal organs, splenomegaly, mesenteric lymph node hyperplasia and inflammatory changes in the thoracic cavity were observed in dead animals of the 200 mg/kg group. Similar pathological changes were observed in a few survival cases of the 200 mg/kg group. 8. After a one month recovery period, the above mentioned changes had mostly recovered, indicating that they were reversible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231787 TI - [Fifty two-week chronic oral toxicity study of mofezolac (N-22) in beagle dogs]. AB - The chronic toxicity study of mofezolac (N-22), a new developed analgesic and anti-inflammatory agent, was carried out in beagle dogs by oral administration of the test compound at dose levels of 1, 3, 6 and 12 mg/kg once daily for 52 weeks. The recovery study was also carried out by withdrawal for 5 weeks. 1. No death occurred during the administration and recovery periods in all groups, there were no abnormal findings due to N-22 administration on behavior and appearance, body weight and food consumption. 2. There were no abnormal findings due to N-22 administration on fecal test, urinalyses, hematological and biochemical examinations, hepatic and renal function tests, ophthalmological examination, electrocardiography, blood pressure and organ weight. 3. By histopathological examination, loss of villi in small intestine was found in one female of 6 mg/kg group, erosion in small intestine in one male of 12 mg/kg group, and shortening of villi and ulcer in small intestine in each one female of 12 mg/kg 4. Accordingly, the non-effective dose levels of N-22 were estimated to be 6 mg/kg for male and 3 mg/kg for female in this study. PMID- 2231788 TI - [Reproductive and developmental toxicity study of mofezolac (N-22) (1)--Study by oral administration of N-22 prior to and early stages of pregnancy in rats]. AB - Mofezolac (N-22), a newly developed analgesic and anti-inflammatory agent, at dose levels of 0, 10, 30 and 90 mg/kg/day were administered orally to males from pre-mating to mating period and to females from pre-mating to early gestation period. Effects on reproductive performance of both sexes, especially reproductive capability, and development of offspring were examined. 1. In male parents, no changes in body weight and food consumption were found in all male groups, but the increase in gastric mucosal lesions such as ulcers were observed in 30 and 90 mg/kg/day groups. 2. In female parents, the decrease in body weight and food consumption of 90 mg/kg/day group during early gestation period were found, but at necropsy no changes were shown in all female groups. 3. Reproductive capability, mating and pregnancy performance were not affected. 4. No effects of N-22 on fetuses were observed. 5. The suggestions were as follows: No effect dose levels (NOELs) for male and female general-toxicologically were 10 and 30 mg/kg/day, respectively. NOELs for reproductive capability and for fetal development were 90 mg/kg/day. PMID- 2231789 TI - [Reproductive and developmental toxicity study of mofezolac (N-22) (2)--Study by oral administration of N-22 during the period of fetal organogenesis in rats]. AB - The teratogenicity of mofezolac (N-22), a new developed analgesic and anti inflammatory agent, was investigated in rats. N-22 was given orally to pregnant rats of the Jcl: Wistar strain (30 rats per group) at dose levels of 10, 50, 100 and 150 mg/kg/day from days 7 to 17 of gestation. Caesarean sections were performed on 20 dams per group on day 20 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. The remaining 10 dams per group were allowed to deliver and their offspring were examined for growth and reproductive performance. Results were as follows. 1. Effects on F0 generation At 150 mg/kg, eleven out of the 30 dams exhibited decreased motor activity, pale eyes, unkempt fur, urine-smeared lower abdomen, weakness and emaciation. At autopsy, twelve dams revealed gastrointestinal ulcers, peritonitic lesions, hypertrophy of the spleen, adrenal and mesenteric lymph node, atrophy of the submaxillary gland, thymus and liver and discoloration of the liver and kidney. Death, sacrificing in extremis, premature or delayed delivery and poor nursing occurred in one to two dams each. Food consumption was significantly decreased and body weight gain was significantly retarded in this dose level group. At 100 mg/kg, urine-smeared lower abdomen, hypertrophy of the spleen and poor nursing were observed in one dam each. 2. Effects on F1 generation At 150 mg/kg, significantly decreased fetal weight, increased number of immature fetuses and significantly retarded ossification of the 5th and 6th sternebrae and coccygeal vertebrae as well as significantly depressed body weight gain of female offspring were observed. No abnormalities were observed in each treated group in terms of development, behavior, learning ability and reproductive performance of offspring. 3. Effects on F2 generation No abnormalities were observed in fetuses and newborn young in each treated group. Based on these results, the maximum non effective doses of N-22 in this study were considered to be 50 mg/kg/day for dams and offspring and 100 mg/kg/day for fetuses. PMID- 2231790 TI - [Reproductive and developmental toxicity study of mofezolac (N-22) (3)- Teratogenicity study in rabbits by oral administration]. AB - Mofezolac (N-22) is a new developed analgesic and anti-inflammatory agent. A teratogenicity study of N-22 was carried out in New Zealand White rabbits to examine the effect on the dams and the teratogenic potentiality. N-22 was administered orally at the dose levels of 12.5, 50 and 200 mg/kg during the organogenesis from day 6 to day 18 of gestation. All pregnant females were sacrificed on day 28 of gestation and their fetuses were examined. There were no growth retardation and teratogenic effects on fetuses from the dams administered N-22, although the administration of 200 mg/kg produced a decrease in food consumption of the dams concomitant with the embryocidal effects as shown by an increase in the early resorption rate. Thus, non-toxic dose level of N-22 on the dams and fetuses was considered to be 50 mg/kg. PMID- 2231791 TI - [Reproductive and developmental toxicity study of mofezolac (N-22) (4)--Study by oral administration of N-22 during the perinatal and lactation periods in rats]. AB - peri- and postnatal study of mofezolac (N-22), a new developed analgesic and anti inflammatory agent, was carried out with Wistar rats. N-22 at dose levels of 0, 25, 50 and 100 mg/kg/day were administered orally to pregnant and subsequent delivered dams from day 17 of gestation through day 21 of lactation. Body weight gains of dams treated with 50 and 100 mg/kg/day were depressed during perinatal period. Prolongation of pregnancy period, low performance of pup care with decrease in body weights and food consumptions were observed in 100 mg/kg/day group. Decrease in number and birth index, increase in number of stillborns and tendency to decrease in viability index on day 4 were found in 100 mg/kg/day group. Other parameters of development, behavior or reproductive capability of F1 animals showed no changes related to administration of N-22. It was suggested that no effect dose levels of N-22 were 25 mg/kg/day for dams viewpoint of general toxicity and that was 50 mg/kg/day for dams on reproductive performance and for offspring on development. PMID- 2231792 TI - Mutagenicity tests of mofezolac (N-22). AB - 1. The reverse mutation test was carried out on mofezolac (N-22) at dose range of 50-5000 micrograms/plate using Salmonella typhimurium strains, TA100, TA98, TA1535 and TA1537, and Escherichia coli strain WP2uvrA. In all tester strains no significant increases were observed in the number of revertant colonies as compared with solvent control in the absence or presence of mammalian metabolic activation system. 2. The chromosomal aberration test on N-22 was carried out using cultured Chinese hamster lung cells (CHL). The cells were treated with N-22 at the doses of 37.5, 75.0, 150 and 300 micrograms/ml without S9 Mix and at the doses of 150, 300, 450 and 600 micrograms/ml with S9 Mix. No significant differences were found in the incidence of structural-and numeral-aberrations of chromosomes as compared with the solvent control in the system without S9 Mix. However, in the system with S9 Mix, structural aberration (11.5%) and numeral aberration (14.2%) of chromosomes were observed in the groups of dosing 600 micrograms/ml with dose dependency. 3. These results indicate that N-22 has clastogenic activity by the metabolic activation. PMID- 2231793 TI - Micronucleus test of mofezolac (N-22). AB - A micronucleus test using BDF1 male mice was conducted in order to evaluate the in vivo mutagenicity of mofezolac (N-22). N-22 was orally administered at doses of 75, 150, 300 and 600 mg/kg, with a sampling time of 24 hr. The frequency of polychromatic erythrocytes with micronuclei was 0.07-0.08% in the groups treated with N-22 and did not differ markedly from that of the vehicle control (0.13%). The present study indicates that N-22 has no in vivo mutagenic properties. PMID- 2231794 TI - [Antigenicity test of mofezolac (N-22)]. AB - Antigenicity studies of mofezolac (N-22) were examined in mice and guinea pigs and the following results were obtained. The findings of active systemic anaphylaxis, passive hemagglutination test, 4 hour passive cutaneous anaphylaxis (4-hr PCA) and 8-day PCA in guinea pigs revealed that N-22 possessed neither immunogenic nor eliciting potentiality. However, N-22 was shown to be eliciting antigenicity in mice when given N-22-ovalbumin conjugate plus Freund's complete adjuvant (FCA) as immunogen. PMID- 2231795 TI - [Three-month subacute oral toxicity study of mofezolac (N-22) in dogs]. AB - Mofezolac (N-22) is a new developed analgesic and anti-inflammatory agent. A subacute oral toxicity test of N-22 was carried out at dose-levels of 0, 2, 6 and 20 mg/kg/day using male and female beagle dogs. Treatment for 3 months was followed by 1 month recovery period except in the case of both sexes receiving 20 mg/kg/day. The results obtained from the present study were as follows. 1. Observation of general conditions revealed vomiting, sporadic bloody feces, anemia, recumbency and hyposthenia in both sexes receiving 20 mg/kg/day. Anemia or erosion of tongue was observed in each female receiving 6 mg/kg/day. 2. Respectively 3 dogs of both sexes receiving 20 mg/kg/day died during dosing period. In these animals, perforating ulcers were observed in the pars pylorica ventriculi or duodenum, and loss of blood, peritonitis and aggravation of general exhaustion were considered as causes of death. 3. Body weight tended to decrease in both sexes receiving 20 mg/kg/day, and food and water consumption levels decreased in males receiving 2 mg/kg/day or above and females receiving 2 mg/kg/day. 4. Urinalysis demonstrated an increasing tendency for specific gravity of urine and a decreasing tendency for urine volume in males receiving 2 mg/kg/day or above. 5. Hematological examination showed decreases in red blood cell count and Hb concentration in males receiving 2 mg/kg/day or above, and in Ht values in males receiving 6 mg/kg/day or above. 6. Serum biochemical examination revealed decreases in total protein and albumin in both sexes receiving 20 mg/kg/day. 7. There were no remarkable changes in hepatic and renal function, ophthalmological findings or electrocardiogram. 8. In the organ weights, significant decrease in thymus weights was observed in the dead animals receiving 20 mg/kg/day. 9. Pathologically, the dead animals receiving 20 mg/kg/day were found to exhibit peritonitis with perforating ulcers in the pars pylorica ventriculi or duodenum. In the surviving animals of this group, scar ulcers in the pars pylorica ventriculi and small intestine were evident on necropsy, and histopathology revealed neutrophils infiltration and thrombosis in blood vessels in the thickened submucosal stomach tissues. Moreover, localized hepatocyte necrosis and intrasinusoidal cellular infiltration in liver, as well as interstitial cellular infiltration, degeneration and dilatation of the renal tubules in the kidney were observed. In females receiving 6 mg/kg/day, the changes in kidney were similar to those in surviving animals receiving 20 mg/kg/day, and male of the group showed atrophy of thymus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2231796 TI - [Fifty two-week chronic oral toxicity study of mofezolac (N-22) in rats]. AB - Fifty two-week oral toxicity study of mofezolac (N-22), a new developed analgesic and anti-inflammatory agent, was carried out in Wistar rats with dose levels of 5, 20, 60 and 120 mg/kg/day, and the 5-week withdrawal was followed for recovery study. Hematuria, blanching of the skin and suppression of body weight gain were observed in females given 120 mg/kg, and 9 of these prostrated and died from week 20 to week 52, or were euthanized when moribund. These symptoms were not seen in males at any dose levels. In 120 mg/kg group, increased positive cases of fecal occult blood were observed during the administration period, and the pathological examination revealed gastrointestinal lesions such as erosion, ulcer, hemorrhage and mucosal regeneration in the small intestine. Renal disorder was also involved mainly in females given 120 mg/kg, as shown by increase in urine volume with declined osmotic pressure and specific gravity, serum urea nitrogen, creatinine, inorganic phosphorus, and other related parameters. In addition to enlargement, rough surface and scar formation, dilated tubular lumen and papillary ducts of the kidney were observed as a main lesion. Incidental findings with those disorders, observed mainly in females given 120 mg/kg, included increase in leucocytes with high neutrophils ratio, and enlargement of the spleen, adrenals and mesenteric lymph node. There were some of the similar gastrointestinal and renal changes mainly in females given 60 mg/kg. Anemic findings were noted in both sexes of 120 mg/kg and in females of 60 mg/kg group, and mainly females given 120 mg/kg showed increase in platelets, reticulocytes and fibrinogen, shortening of blood coagulation time, as well as extramedullary or accented hematopoiesis of the liver, spleen and bone marrow. Other serum biochemical changes observed mainly in females given 120 mg/kg were decrease or decreasing trend in total protein, A/G ratio, and transaminase activity. Fine structure of the liver from females given 20 mg/kg or more revealed cisternal dilatation of smooth-surfaced endoplasmic reticulum of hepatocytes, and the increased liver weight was observed in females given 120 mg/kg. Accordingly, non-effective dose level of N-22 in 52-week chronic toxicity study was estimated to be 20 mg/kg for males and 5 mg/kg for females. PMID- 2231797 TI - The way we were: 1989 Presidential address, American Association for the Surgery of Trauma. PMID- 2231798 TI - Auto-PEEP in the multisystem injured patient: an elusive complication. AB - Auto-PEEP (A-PEEP), unrecognized alveolar positive and expiratory pressure during mechanical ventilation, is an acknowledged hazard in patients with chronic obstructive lung disease. We evaluated 50 consecutive trauma patients for the presence of A-PEEP and its effect on hemodynamic stability. Injury Severity Scores (ISS) were 8 to 41 (21 +/- 1); Revised Trauma Scores (RTS) ranged from 2.0 to 7.8 (6.2 +/- 0.2). Mode of ventilation was assist control, inspiratory flow rates were 40 to 120 L/M (78 +/- 2). A-PEEP, determined in the non-assisting patient by occluding the expiratory port at end exhalation, was present in 28 patients (56%) and ranged from 1 to 12 cm H2O (5.3 +/- 0.4 cm H2O). Data segregated by A-PEEP versus no A-PEEP were as follows (Mean +/- SEM): [table: see text] *P less than 0.05, VE = minute ventilation, Paw = mean airway pressure. Upon reversal of A-PEEP in the eight patients with levels greater than 5 cm H2O, mean blood pressure rose from 90 +/- 17 to 102 +/- 22 mm Hg and central venous pressure fell from 13 +/- 5 to 7 +/- 5 mm Hg. A-PEEP was successfully treated in these eight patients by increasing peak flows, minimizing VE requirements and selective use of bronchodilators. In sum, the hypermetabolic ventilated trauma patient should be monitored routinely for this common phenomenon which may have profound cardiopulmonary effects in the setting of acute resuscitation. PMID- 2231799 TI - Gunshot injuries to the hip and abdomen: the association of joint and intra abdominal visceral injuries. AB - A retrospective review of all gunshot injuries to the hip at our medical center over a 24-year period was performed. Adequate information and radiographs were available for 49 patients. Of these, five patients (10.2%) had associated abdominal visceral injuries. These five patients were examined at an average of 5.9 years after their injury, and compared by utilizing the Harris Hip Score rating. Radiographs were also obtained. Four of these five patients (80%) had initially developed infections in their hip joints, with all four having poor functional outcomes, with an average Harris Hip Score of 48.5 from their hip injury. Careful initial evaluation and aggressive surgical and antibiotic treatment are recommended to prevent these poor results. PMID- 2231800 TI - Effect of endotoxin and a burn injury on lung and liver lipid peroxidation and catalase activity. AB - Both endotoxin and a burn alone produce oxidant-induced tissue lipid peroxidation. The endotoxin response is due in large part to hydrogen peroxide. The combination of endotoxin after a burn results in an increased liver, but not lung, oxidant injury. Our purpose was to determine whether the burn oxidant injury inactivated endogenous liver tissue catalase, thereby amplifying a subsequent H2O2 insult. Twenty-six adult sheep were studied. Twelve sheep had a 15% TBS burn. Tissue catalase activity, measured in lung and liver 3 days postburn, was significantly decreased from a control of 3.58 +/- 1.8 and 193 +/- 63, respectively, to 1.72 +/- 0.63 and 148 +/- 33 k(sec-1)/0.5 gram tissue. The addition of endotoxin 3 days postburn resulted in an increase in liver malondialdehyde, MDA, a measure of lipid peroxidation, from a control of 110 +/- 80 to 450 +/- 54 nmol/gram tissue. This value was significantly greater than the 210 +/- 80 nmol/gram tissue seen after endotoxin alone. Lung tissue MDA with burn and endotoxin was 65 +/- 8 compared to 42 +/- 7 for control and 80 +/- 6 nmol/gram for endotoxin alone. We conclude that a decrease in liver catalase activity occurs after a burn. The decrease corresponds to an accentuated oxidant induced lipid peroxidation after an added endotoxin insult where H2O2 is known to be an etiologic agent. The catalase activity also decreases in postburn lung, but accentuated lung damage was not seen, indicating a variable tissue response from the burn-induced decrease in antioxidant activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231801 TI - Facial bone fracture associated with carotid-cavernous sinus fistula. AB - Out of 989 cases of facial bone fracture, ten patients had carotid-cavernous sinus fistulas (1.01%). Their ages ranged from 25 to 48 years. Seven were male and three female. Two of the ten patients had lower third, three patients had middle third, three patients had upper third, and two patients had combined middle and lower third facial bone fractures. The signs and symptoms of a fistula appeared from the first postinjury day up to 50 days after the injury (mean, 21 days). Four patients had symptoms after operation for facial bone fracture. Most fistulae were identified by arteriography before treatment. Followup ranged from 1 year, 8 months, to 5 years, 9 months (mean, 2 years, 9 months). One patient had a malocclusion. Nine patients had complete resolution of their bruits. Complications included unilateral complete visual loss (two), CSF rhinorrhea (two), and stroke in one of the two CSF rhinorrhea patients. One patient expired due to a severe head injury, and there was one death from an unrelated cause. PMID- 2231802 TI - The abdominal trauma index--a critical reassessment and validation. AB - The Abdominal Trauma Index (ATI) was devised to quantify the risk of complications following abdominal trauma. With scores greater than 25, the risk of postoperative complications became exponential. The purpose of the present study was to determine if: 1) the organ risk factors previously assigned were more statistically valid; and 2) the addition of physiologic variables would enhance the prediction of postinjury intra-abdominal sepsis. Fifteen abdominal organ systems and 17 physiologic variables in 300 consecutive patients were analyzed to determine ability to predict intraabdominal sepsis. There were no significant differences in predictive ability between the old and new organ risk factors. The addition of physiologic factors did not enhance the prediction of intra-abdominal sepsis. This clinical study demonstrates that: 1) the risk of intra-abdominal sepsis increases with increasing ATI score; 2) the previous (1979 initial) organ risk grading concept is statistically valid; 3) six of the 15 organ systems warrant a change in their relative rank order (1989-revision); 4) the addition of demographic, physiologic, and immunologic variables did not significantly improve the prediction of intra-abdominal sepsis. PMID- 2231803 TI - Diagnostic peritoneal lavage: accuracy in predicting necessary laparotomy following blunt and penetrating trauma. AB - The purpose of this study was to evaluate the ability of diagnostic peritoneal lavage (DPL) to predict intra-abdominal injuries that required surgical repair. To do this, we retrospectively reviewed 944 patients with blunt and penetrating abdominal trauma who underwent 975 DPLs. Initial DPL in 608 patients sustaining blunt trauma had a sensitivity of 87%, a specificity of 97%, an accuracy of 95%, a positive predictive value (PPV) of 85%, and a negative predictive value (NPV) of 97%. Initial DPL in 336 patients with penetrating trauma had a sensitivity of 87%, a specificity of 89%, an accuracy of 89%, a PPV of 75%, and a NPV of 95%. When utilizing final lavage results on the 944 patients, DPL had a sensitivity of 91%, a specificity of 94%, an accuracy of 93%, a PPV of 80%, and a NPV of 98% in predicting intra-abdominal injury requiring surgical repair. PMID- 2231804 TI - The Major Trauma Outcome Study: establishing national norms for trauma care. AB - The Major Trauma Outcome Study (MTOS) is a retrospective descriptive study of injury severity and outcome coordinated through the American College of Surgeons' Committee on Trauma. From 1982 through 1987, 139 North American hospitals submitted demographic, etiologic, injury severity, and outcome data for 80,544 trauma patients. Motor vehicle related injuries were most frequent (34.7%). Twenty-one per cent of patients had penetrating injuries. The overall mortality rate was 9.0%. The mortality rate for direct admissions was strongly related to the presence of serious head injury, 5.0% and 40.0%, when head injuries were less than or equal to AIS (Abbreviated Injury Scale) 3 or greater than or equal to AIS 4, respectively. Survival probability norms use the Revised Trauma Score, Injury Severity Score, patient age, and injury mechanism. Patients with unexpected outcomes were identified and statistical comparisons of actual and expected numbers of survivors made for each institution. Results provide a description of injury and outcome and support evaluation and quality assurance activities. PMID- 2231805 TI - Cadaveric organ donor availability: regional trauma center vs. community hospital. AB - Organ donor shortage is now the greatest limitation to the success of organ transplantation. To assess and compare the role of a regional trauma center in identifying and referring cadaveric organ donors to that of a community hospital, we retrospectively reviewed records of potential cadaveric organ donors during a comparable 5-year period in each. The trauma center (TC) contributed 44 donors, while the community hospital (CH) supplied seven. Five hundred sixty-five possible donors were not harvested at the TC, compared to 126 at the CH. While most "non-donors" from both institutions were not suitable candidates, 8% could have served as good organ donors. Inability to obtain consent was the major obstacle in obtaining good candidates (70% at CH, 83% at TC). Failure to recognize and refer possible donors occurred in 2% of the cases at CH, compared to 0.4% at the TC. We conclude that regional trauma centers can play an important role in alleviating organ donor shortage. PMID- 2231806 TI - Studies on B-lymphocyte dysfunctions in severely burned patients. AB - We studied in vitro functional parameters of peripheral blood B-lymphocytes from severely burned patients (n = 10; burn injuries ranging from 25 to 72% TBSA). While the number of B-cells remained unchanged, B-cell proliferation induced by Staphylococcus aureus strain Cowan I (SAC) was normal or even enhanced at early and late phases postburn, but showed a marked suppression during the second to fourth week. A similar pattern was observed for the pokeweed mitogen (PWM)- or SAC-stimulated synthesis of immunoglobulin M (IgM), whereas IgG production was decreased over the whole postburn period monitored. Cytokine (interleukin 4) induced B-cell activation as indicated by the expression of the CD23 surface antigen was impaired throughout the second to fifth week. In parallel, the release of the proteolytic cleavage product sCD23 which represents a B-cell growth and differentiation factor was reduced. Our data provide evidence that activation, proliferation, and differentiation processes of B-lymphocytes are impaired in severely burned patients, which may contribute to their enhanced susceptibility to infection and sepsis. PMID- 2231807 TI - Parotid gland and facial nerve trauma: a retrospective review. AB - Included in this study are all patients with trauma to the parotid region seen at our center from 1979 to 1989. There was a total of five patients with injury to the parotid area: two patients with isolated facial nerve injury; one with isolated parotid duct injury; two with combined duct and nerve injury. There were four males and one female, with a mean age of 34 years (range, 16 to 62 years). The three patients with parotid duct injury required other procedures for associated trauma. A total of eight nerve branches were severed in four patients. Seven of the eight nerve branches (82.5%) were primarily repaired, with excellent functional results. Two of the three ductal injuries were repaired primarily over a stent, and one was ligated. No complications resulted from either treatment. Based on our clinical experience and review of the literature, we suggest that the treatment of parotid region injuries should include: 1) a complete initial assessment; 2) primary repair of parotid duct transection within 24 hours when possible; 3) primary repair of all facial nerve injuries, although delayed nerve repair remains a viable alternative; and 4) nonsurgical treatment of sialoceles and fistulae. PMID- 2231808 TI - Subxiphoid pericardial windows--helpful in selected cases. AB - There is a small group of patients who sustain multiple penetrating injuries who present with haemodynamic changes, making it difficult to clinically exclude or prove the presence of penetrating cardiac injury. It is in this select group of patients that we found subxiphoid pericardial windows to be extremely useful to prove or disprove the existence of a cardiac injury and thereby prevent a delay in diagnosing these injuries. PMID- 2231809 TI - Bilateral sacroiliac joint fracture-dislocation: a case report. AB - Bilateral sacroiliac joint fracture-dislocation of the sacrum with displacement is a rare injury. We found only four such injuries previously reported in the literature. Nonoperative management in this case led to complete functional return and acceptable alignment. PMID- 2231810 TI - Use of recombinant human erythropoietin (r-HuEPO) in a Jehovah's Witness refusing transfusion of blood products: case report. AB - Recombinant human erythropoietin (r-HuEPO) administration to a Jehovah's witness refusing blood transfusions increased her nadir packed cell volume from 13% to 37% and reticulocyte count from 2% to 17.7%. R-HuEPO may provide an alternative safe and effective therapy in life-threatening anemia when blood transfusions are unacceptable to the patient. PMID- 2231811 TI - Pediatric blunt liver injury and coagulopathy managed with packs and a silo: case report. AB - Packing the abdomen can be lifesaving when severe hepatic trauma is complicated by refractory hypothermia, coagulopathy, and continuing hemorrhage requiring large-volume transfusion. This report describes the successful use of abdominal packs and a modified silo in a child following blunt liver injury. PMID- 2231812 TI - Acute aortic valvular incompetence following blunt thoracic deceleration injury: case report. AB - Blunt trauma leading to aortic valvular incompetence is rarely encountered, with 27 cases reported to date. All cusps and commissures are involved to a similar degree. Treatment includes either reattachment of cusps to the annulus (80% recurrence of incompetence) or valvular replacement (no recurrence). Valve replacement is the treatment of choice for these patients. PMID- 2231813 TI - Brachial plexus injury associated with chest restraint seatbelt: case report. AB - Rapid deceleration while wearing a lap-shoulder strap seatbelt may result in a traction injury to the brachial plexus on the side of the shoulder strap. Occult vascular injury should be considered in patients with this injury pattern. The deficit will recover after a neuropraxic type injury. PMID- 2231814 TI - Bilateral simultaneous fractures of the femoral neck: case report. AB - A case of bilateral fractures of the femoral neck resulting from high-voltage electric injury is reported. Surgeons caring for patients with electrical injuries must be aware of the possibility of this injury as well as other skeletal injuries which may result from muscle contraction or falls related to electric shock. Without vigilance for these injuries, diagnosis may be delayed. PMID- 2231815 TI - Hypogastric arterial embolization in pelvic fracture hemorrhage: case report. PMID- 2231816 TI - Impact of pre-trauma center care on length of stay and hospital charges. PMID- 2231817 TI - Morbidity and mortality following fractures of the femoral neck and trochanteric region: analysis of risk factors. PMID- 2231818 TI - Acute compartment syndrome of the thigh: case report. PMID- 2231819 TI - Endoscopic guided percutaneous tracheostomy: early results of a consecutive trial. PMID- 2231820 TI - The mortality of childhood falls. PMID- 2231821 TI - Response to inquiries regarding the exact formulary constituents of Betadine solution. PMID- 2231822 TI - Organ injury scaling, II: Pancreas, duodenum, small bowel, colon, and rectum. AB - The Organ Injury Scaling (O.I.S.) Committee of the American Association for the Surgery of Trauma (A.A.S.T.) has been charged to devise injury severity scores for individual organs to facilitate clinical research. Our first report (1) addressed O.I.S.'s for the Spleen, Liver, and Kidney; the following are proposed O.I.S.'s for Pancreas (Table I), Duodenum (Table II), Small Bowel (Table III), Colon (Table IV), and Rectum (Table V). The grading scheme is fundamentally an anatomic description, scaled from 1 to 5, representing the least to the most severe injury. We emphasize that these O.I.S.'s represent an initial classification system which must undergo continued refinement as clinical experience dictates. PMID- 2231823 TI - Eating disorders: a primer for the substance abuse specialist: 1. Clinical features. AB - The eating disorders of anorexia nervosa (AN) and bulimia nervosa (BN) are no longer rare or esoteric syndromes. Because they affect about 5% of young adult women in westernized societies, and because there is a greater than chance co morbidity with substance abuse disorders, it has become increasingly important for the substance abuse specialist to be knowledgeable about AN and BN. This paper will describe the epidemiologic, clinical, diagnostic, and prognostic features of the two eating disorders; a subsequent paper will examine theories of etiology and approaches to treatment, and discuss the special considerations that pertain when co-morbidity with substance abuse is indeed present. PMID- 2231824 TI - Alcoholic blackouts: legal implications. AB - Alcoholic blackouts are defined as the temporary, complete inability to form long term memory as the result of a high blood alcohol level. This means that a neuron to-neuron system has been blocked. Since that is the case, such central nervous dysfunction should have legal implications, both from the blackout itself and also from the fact that this degree of neural interference in one system is at least suggestive that other dysfunction may be present. The subject of blackouts is updated with recent developments in neuroscience. The legal significance of the blackout is examined in enough depth to allow for further discussion and exploration. PMID- 2231826 TI - The role of buspirone in the management of alcohol withdrawal: a preliminary investigation. AB - One hundred eighteen patients, 77 men and 23 women ranging in age from 18 to 70 years of age, admitted to an inpatient facility in Central New York were administered buspirone HCl for treatment of the alcohol withdrawal syndrome. Although one patient had an unwitnessed seizure, none of the subjects required discontinuance of buspirone HCl because of symptoms of dizziness, nausea, headache, nervousness, or lightheadedness, typical side effects described by the manufacturer. All but one of the individuals given buspirone HCl for alcohol detoxification completed that phase of treatment within six days in a manner which effectively controlled their withdrawal symptoms. The findings were suggestive of an important role for buspirone HCl in the detoxification of the alcohol-dependent patient using a pharmacologic agent other than traditional medications such as benzodiazepines, phenobarbital, beta blockers, magnesium sulphate, or clonidine. PMID- 2231825 TI - Cranial electrostimulation (CES) use in the detoxification of opiate-dependent patients. AB - This paper reviews the scientific literature on cranial electrostimulation (CES) as a non-chemical means to alleviate opiate withdrawal symptoms. CES involves applying small amounts of electrical stimulation through electrodes applied to the skin surface over the cranium. The paper summarizes major theories (gate, endorphin, and Chinese acupuncture) which attempt to explain how CES may help alleviate drug withdrawal and craving. Two of the studies reviewed show that CES patients experienced more severe withdrawal during the early part of treatment than comparison groups of methadone patients. Other studies show that CES patients did better than methadone patients. The findings from all studies reviewed, however, were limited because of low participation rates, high dropout rates, difficulties in blinding subjects and evaluators, and the absence of standardized procedures and equipment. The evidence reviewed suggests that CES is a promising line of inquiry for continued efforts to develop nonchemical ways to detoxify opiate-dependent individuals. Improved research designs, larger sample sizes, more integrity in data collection, and improved data analysis are needed in the future. PMID- 2231827 TI - In memorium. Kenneth F. Lampe. PMID- 2231828 TI - ATSDR (Agency for Toxic Substances and Disease Registry) case studies in environmental medicine. Vinyl chloride toxicity. PMID- 2231829 TI - Anabolic steroids--a review of the clinical toxicology and diagnostic screening. AB - Anabolic steroids have been used by athletes since the 1950s to increase size and strength in order to improve their performance. The abuse of these substances has since expanded to include junior high and high school male and female athletes and non-athletes. The anabolic and androgenic effects of these agents, when taken in the doses needed to produce increases in size and strength, result in significant serious adverse effects involving the skin, liver, cardiovascular, musculoskeletal, endocrine and reproductive systems. Some of these effects are irreversible. It is essential that clinical toxicologists, emergency room physicians and psychiatrists are familiar with the physical and psychological effects, as well as the changes in laboratory parameters, that typically occur from chronic use of anabolic steroids. The toxicities and representative clinical profiles of steroid users are presented, and the methods available for diagnostic screening using psychological testing and urine analysis are also reviewed. PMID- 2231830 TI - Gastrointestinal pathology in adult iron overdose. AB - The gastrointestinal effects of iron overdose have been described in children. They may occur acutely, ranging in severity from mucosal injury to complete infarction, or several weeks later, as obstruction due to stricture formation. They typically occur in the stomach or proximal small bowel. We describe an adult example of both, each occurring in the distal portion of the small intestine. Both patients had ingested enteric-coated iron preparations and both experienced significant, protracted abdominal pain. Thus adults as well as children are at risk for severe gastrointestinal complications after iron overdose. Significant protracted abdominal pain should alert the clinician of its possibility. Damage to distal areas of the bowel can occur with complete sparing of proximal portions particularly if the iron is an enteric-coated preparation. PMID- 2231831 TI - Rhabdomyolysis and acute renal failure associated with cocaine abuse. AB - Cocaine abuse has emerged as a major public health problem among young adults. Illicit use of cocaine has been associated with an increasing array of medical complications. Both traumatic and nontraumatic rhabdomyolysis, often complicated by acute renal failure, has recently been described following cocaine abuse. The present report describes our experience with 15 such patients and serves to further define the spectrum of muscle injury associated with cocaine abuse ranging from the incidental finding of elevated serum levels of muscle enzymes to acute renal failure. Those patients who developed renal failure experienced more severe rhabdomyolysis in association with trauma, seizures or hyperpyrexia. PMID- 2231832 TI - The effects of fluoxetine in the overdose patient. AB - Fluoxetine (Prozac) is a new antidepressant, first marketed in the United States in January 1988. Only limited toxicologic information during a fluoxetine overdose is available. The goal of this prospective multi-center study was to develop a toxicity profile of initial signs and symptoms observed in fluoxetine overdose. A standardized data collection form was used on all patients ingesting fluoxetine as reported to four poison centers. Information obtained included age, dose, co-ingested drugs, presenting symptoms, vital signs, EKG abnormalities and lab values. Of the 127 cases of acute fluoxetine overdose collected, 106 cases met the criteria of the study. Of these, 69/106 ingested other drugs, including ethanol and 37/106 ingested fluoxetine alone. Of the latter group, the amounts ingested ranged from 20 to 1500 mg. It was observed that 48.6% (18/37) remained asymptomatic, 16.2% (7/37) were sleepy, 24.3% (9/37) had a sinus tachycardia (of 100 beats per minute or greater), and 8.1% (3/37) had a diastolic pressure over 100 mm Hg. Data collection is ongoing. Based upon our initial experience, fluoxetine in overdose appears to be relatively benign. PMID- 2231834 TI - Toxicological screening: a three year experience in poisonings in Kuwait. AB - The results of toxicological screening of body fluids (urine, blood and gastric lavage) from pediatric patients were analyzed for the period January 1985 - December 1988. Of the 119 cases, approximately one half were positive for at least one foreign substance. In about one fifth of the cases, multiple substances were detected. The most commonly implicated drugs were those acting on the central nervous system including the barbiturates, tricyclic antidepressants, phenothiazines, benzodiazepines and carbamazepine. PMID- 2231833 TI - Clinical experience with the benzodiazepine antagonist flumazenil in suspected benzodiazepine or ethanol poisoning. AB - The clinical efficacy of different doses of the specific benzodiazepine antagonist flumazenil was studied in a total of 72 patients with benzodiazepine or ethanol overdose. In a randomized double-blind study, 18 patients (group 1) and eight patients (group 2) with suspected benzodiazepine overdose received 5 mg (group 1) or 1 mg (group 2) flumazenil or placebo, respectively. The stage of coma, heart rate, blood pressure and respiratory rate were monitored within the following 15 min. If no change in the stage of coma was observed, 5 mg (group 1) or 1 mg (group 2) flumazenil were given, and the stage of coma, heart rate and blood pressure were again monitored. In a similar way, the effect of 5 and 1 mg flumazenil was investigated in 13 patients (group 3) and four patients (group 4) with ethanol intoxication. In an open trial, the clinical efficacy of flumazenil for the diagnosis of benzodiazepine or ethanol overdose was studied in 29 patients (group 5). In all patients, a toxicological screening confirmed benzodiazepine or ethanol overdose. None of the patients receiving placebo showed effects on stage of coma, heart rate, blood pressure or respiratory rate. Patients with benzodiazepine overdose who received 5 mg flumazenil regained consciousness about 1-2 min after the end of injection. The effect of 1 mg flumazenil (group 2) on benzodiazepine-induced coma was less pronounced. In patients with ethanol overdose (group 3), ethanol-induced coma was reversed after 5 mg flumazenil more slowly than in patients of group 1. No effect of flumazenil on ethanol-induced coma was observed in group 4. In group 5, flumazenil proved to be useful for diagnosing benzodiazepine or ethanol intoxication. In one patient with coma due to carbamazepine overdose, flumazenil was also found to be effective. Additionally, a possible analytical interference of flumazenil and its metabolites with the identification of other benzodiazepines by a toxicological screening procedure was studied. Even after an oral dose of 200 mg flumazenil, no interference with immunological benzodiazepine assays (EMIT, TDX, and RIA) was found. A metabolite and an artifact of flumazenil could be identified in urine by gas chromatography/mass spectrometry. PMID- 2231835 TI - Morphine excretion in breast milk and resultant exposure of a nursing infant. AB - We report the case of an infant who was breastfed while his mother was receiving low doses of morphine. Morphine concentration in his serum was in the analgesic range (4 ng/ml), while concentrations in the milk varied substantially in three samples collected within 2 hours (10, 100, 12 ng/ml). The calculated dose that the infant must have received to achieve the observed serum concentration had to be between 0.8 to 12% of maternal dose, based on reference literature values of clearance and bioavailability. The current perception that maternal morphine exposure is safe for the breastfed infant is based on a 50 year old data which were determined by an analytical method 1000 fold less sensitive than the present HPLC, thus leading to a likely erroneous conclusion. PMID- 2231836 TI - Clinical course and pharmacokinetics following a massive overdose of amphotericin B in a neonate. AB - Amphotericin is the drug of choice for the treatment of fungal infections in infants and children. When used in the recommended doses, amphotericin therapy is associated with high rates of adverse effects, including nephrotoxicity, hepatotoxicity, decrease in white blood cells, platelets and hemoglobin, chills, fever and even death (1). We report a case involving a neonate who was exposed to a 50 fold overdose of Amphotericin over a three day period. PMID- 2231837 TI - Suicide by captopril overdose. AB - We report a case of a 75 year-old male who committed suicide by taking an overdose of captopril. He took approximately ninety 12.5 mg captopril tablets. The postmortem plasma concentration of captopril was 60.4 mg/L. A review of the medical literature revealed five cases of captopril overdose all from unsuccessful suicide attempts. To our knowledge, this is the first case report of fatal captopril overdose with the measurement of plasma concentration of the drug. PMID- 2231838 TI - Skin blisters as a manifestation of oxazepam toxicity. AB - A 75 year-old comatous patient was admitted after ingestion of 200 mg oxazepam. Skin blisters, attributed to oxazepam toxicity, appeared on the left forearm the following day and regressed spontaneously nine days later. PMID- 2231839 TI - Compliance with malaria chemoprophylaxis over a five-year period among children in a rural area of The Gambia. AB - We have reviewed a malaria chemoprophylaxis programme in which Maloprim (pyrimethamine and dapsone) has been administered fortnightly by village health workers (VHWs) to approximately 1500 children each year aged 6-59 months resident in 15 primary health care villages in a rural area of The Gambia over 5 years. Reasonable levels of compliance with chemoprophylaxis have been maintained by many children over this period. this has occurred despite minimal outside supervision and support of the programme. Factors which may have affected the level of compliance in individual villages are identified. Large villages and those where social or political factionalism were evident tended to have low levels of compliance. The attitudes of VHWs and mothers to the programme were determined. Most VHWs cooperated enthusiastically and kept accurate records of compliance, despite receiving no compensation from the villagers for administering chemoprophylaxis. The administration of a drug to prevent illness in children was complementary to the curative service provided by VHWs. The chemoprophylactic was widely acceptable and nearly all mothers stated that the tablets were good for their children's health. However, knowledge of the specific purpose of chemoprophylaxis in the prevention of malaria was limited. Improvements in the programme which may result in higher levels of compliance are discussed. PMID- 2231840 TI - Androctonus crassicauda sting and its clinical study in Iran. AB - Androctonus crassicauda is the second most frequent cause of scorpion sting in southwest Iran. Its toxin can cause severe pain, autonomic, CNS, and muscle function disturbances, and death. Appropriate medical and nursing care can lead to complete recovery with no sequelae. PMID- 2231841 TI - Clinical study of Hemiscorpion lepturus in Iran. AB - Hemiscorpion lepturus (HL) sting accounts for 10-15% of all scorpion stings in south-west Iran. HL toxin is a cytotoxic and fatal venom which may affect any organ system, especially CNS, cardiovascular, skin and blood cells. Surgical excision of the sting site may prevent harmful or fatal consequences. Corticosteroids, adequate hydration, blood transfusion and diuretics may help some severely envenomed patients; some may die from cardio-respiratory arrest or renal failure. PMID- 2231842 TI - A survey of Ampullarium canaliculatus for natural infection of Angiostrongylus cantonensis in south Taiwan. AB - Ampullarium canaliculatus were collected monthly from the field in five areas in Pintung County and examined for larvae of Angiostrongylus cantonensis. Snails from one area showed the highest positive rate (30.8%) and the highest number (31) of larvae per snail. Snails were placed in four groups according to size. The positive rates in snails increased from 10.0 to 29.4% and the average number of larvae per snail increased from 11 to 40 as the size of snails increased from 1.0 to 4.0 cm height or more. In the seasonal fluctuation of snails in the field, positive snails could be examined every month; however, the positive rate in snails (28.2%) and the average number of larvae per snail (33) in the dry season (November to April) were significantly higher than those (15.2% and 23 respectively) in the rainy season (May to October). Ampullarium canaliculatus were confirmed naturally infected with A. cantonensis in this investigation so more attention should be paid to the snails to prevent the infection in humans. PMID- 2231843 TI - Pattern of alimentary tract tumours in Plateau State: a middle belt area of Nigeria. AB - Forty-five neoplastic surgical specimens from the alimentary tract were studied in Jos University Teaching Hospital, Jos, Plateau State, Nigeria, over a 5-year period (1983-1987). Rectal carcinomas were found to be the commonest alimentary tract tumours (28.9%). They are followed by carcinomas of the stomach (24.4%), colon (20.1%) and oesophagus (13.3%). Lymphomas constitute 6.7% while squamous cell carcinomas of the anus represent 2.2%. PMID- 2231844 TI - High prevalence of giardiasis in an urban population in Niger. AB - A sample of 2569 persons (1190 m, 1379 f) from Niamey (population 329,000), Niger, showed a giardiasis prevalence of 28.5%. The prevalence was similar between males and females and highest in the age range 3-29 years. PMID- 2231845 TI - Manifestations of Behcet's syndrome from Pakistan. PMID- 2231846 TI - Antimicrobial agent susceptibility patterns of staphylococci isolated in urban and rural areas of Bolivia. AB - Staphylococcal strains obtained from cutaneous swabs of hospital staff and school students of Camiri and Boyuibe and healthy people living in Javillo, Bolivia, were tested for their in-vitro antimicrobial susceptibility. The highest percentages of resistance to the antibiotics tested were found in staphylococcal strains isolated from hospital personnel. All the S. aureus strains from these subjects were resistant to penicillin. Coagulase-negative staphylococci from hospital personnel evidenced a high rate of multiresistant strains, mainly to penicillin, ampicillin, tetracycline, and chloramphenicol. The staphylococcal strains isolated in the rural population of Javillo were highly susceptible to all the antibiotics tested. PMID- 2231847 TI - Endurance running performance in athletes with asthma. AB - Laboratory assessment was made during maximal and submaximal exercise on 16 endurance trained male runners with asthma (aged 35 +/- 9 years) (mean +/- S.D.). Eleven of these asthmatic athletes had recent performance times over a half marathon, which were examined in light of the results from the laboratory tests. The maximum oxygen uptake (VO2max) of the group was 61.8 +/- 6.3 ml kg-1 min-1 and the maximum ventilation (VEmax) was 138.7 +/- 24.7 l min-1. These maximum cardio-respiratory responses to exercise were positively correlated to the degree of airflow obstruction, defined as the forced expiratory volume in 1 s (expressed as a percentage of predicted normal). The half-marathon performance times of 11 of the athletes ranged from those of recreational to elite runners (82.4 +/- 8.8 min, range 69-94). Race pace was correlated with VO2max (r = 0.863, P less than 0.01) but the highest correlation was with the running velocity at a blood lactate concentration of 2 mmol l-1 (r = 0.971, P less than 0.01). The asthmatic athletes utilized 82 +/- 4% VO2max during the half-marathon, which was correlated with the %VO2max at 2 mmol l-1 blood lactate (r = 0.817, P less than 0.01). The results of this study suggest that athletes with mild to moderate asthma can possess high VO2max values and can develop a high degree of endurance fitness, as defined by their ability to sustain a high percentage of VO2max over an endurance race. In athletes with more severe airflow obstruction, the maximum ventilation rate may be reduced and so VO2max may be impaired. The athletes in the present study have adapted to this limitation by being able to sustain a higher %VO2max before the accumulation of blood lactate, which is an advantage during an endurance race. Therefore, with appropriate training and medication, asthmatics can successfully participate in endurance running at a competitive level. PMID- 2231848 TI - Somatotypes of weight lifters. AB - The present paper reviews published studies on the body shape of weight lifters. The differences between the somatotype ratings of weight lifters studied using the Sheldon and the Heath-Carter methods, and the differences between performance levels and age groups of weight lifters are discussed. The differences in mean somatoplots among the weight lifters studied as a whole group, weight lifters divided into two, three or four groups according to body weight, and weight lifters considered according to the official weight classes, are assessed. Weight lifters in the lighter weight classes are found to be ectomorphic or balanced mesomorphs, while those in the heavier weight classes tend to be endomorphic mesomorphs. Ectomorphy decreases, whereas mesomorphy and endomorphy increase with weight class. When three age groups of weight lifters were compared within each weight class, the same pattern of differences between ages occurs. The younger lifters in each weight class have higher endomorphy and lower mesomorphy than the senior lifters. Ectomorphy is higher in the younger lifters below the weight class of 82.5 kg. Since significant differences in all three somatotype components between 10 weight classes of weight lifters and also within three age groups were noted, it will be necessary in future studies to consider the somatotypes of weight lifters according to the official weight classes. PMID- 2231849 TI - The 4 mM blood lactate level as an index of exercise performance in 11-13 year old children. AB - The aim of this study was to assess the use of the 4 mM blood lactate level measured during incremental treadmill exercise as an indicator of exercise performance in 11-13 year old children. Fifty girls and 53 boys (means age 12.2 +/- 0.6 years) gave informed consent to participate in the study. The children completed a discontinuous, incremental running test on a motorized treadmill. A 1 min pause separated the 3 min exercise stages during which time duplicate capillary blood samples were taken for immediate assay of whole blood lactate concentration. Cardiorespiratory variables were measured continuously during exercise using a computerized on-line system. Mean values for peak oxygen uptake were 48 +/- 7 ml kg-1 min-1 and 42 +/- 7 ml kg-1 min-1 in boys and girls respectively. The exercise intensity corresponding to a blood lactate concentration of 4 mM was interpolated from plots of % peak oxygen uptake vs blood lactate and was reached at 91 +/- 7% peak oxygen uptake in both boys and girls. The results indicate that children can exercise at intensities close to their peak oxygen uptake without accumulating high levels of blood lactate and the use of the 4 mM blood lactate level to assess and monitor exercise performance in children of this age may therefore be inappropriate. PMID- 2231850 TI - Psychological characteristics of male gymnasts: differences between competitive levels. AB - The purpose of this study was to examine whether any differences exist in the cognitive and behavioural strategies of gymnasts competing at different elite levels. Thirty-eight male gymnasts competing at different competitive levels in an Australian gymnastic championship completed a standardized questionnaire prior to the first day of the competition. The questionnaire focused on a number of psychological factors that may affect both training and competition. Using both t tests and simple discriminant function analysis, it was revealed that gymnasts competing at different elite levels could be distinguished on the basis of two psychological factors, psychological recovery and self-confidence, as well as the behavioural measure, training hours. Specifically, gymnasts competing at higher elite levels versus those at lower elite levels, were better able to recover from their competitive mistakes, were more confident and trained longer per week. PMID- 2231851 TI - Sports performance. PMID- 2231852 TI - An analysis of the relationship between hostility and training in the martial arts. AB - Contrasting views and data are available on the issue of whether combative sports facilitate or reduce aggression. In the present study levels of hostility were assessed in two groups of martial arts students using the Buss-Durkee Inventory. Levels of hostility on a variety of the sub-scales were compared with scores from similar samples of participants in a body contact, aggressive but non-combative sport (rugby football) and a competitive sport with no body contact or direct aggression (badminton). When the effects of age and length of training were controlled by use of partial correlation there was no evidence to support group differences in either the combined score from the varied sub-scales of the inventory or the more specific assaultive sub-scale. However, there was evidence to suggest a significant effect of length of training on hostility levels in martial artists. Beginners attracted to the martial arts were more hostile but the hostility declined with the duration of training. No difference was apparent in this respect for students participating in either jui jitsu or karate. It is suggested that such differential effects with respect to length of training may lead to the overall absence of the between-sport differences. The results provide tentative support for the notion that the discipline of the martial arts may reduce assaultive hostility rather than serve as a model for such behaviour, yet support the need for prospective longitudinal studies on intra-individual hostility. PMID- 2231853 TI - Coronal biparietal diameter. A reliable alternative to the traditional transverse biparietal diameter. AB - The traditional ultrasonically derived fetal biparietal diameter (BPD) is important in the determination of fetal age, weight, and growth. This measure cannot be obtained, however, with direct occiput anterior or posterior or with a head in the pelvis. This study looked at the BPD utilizing coronal (anatomically at right angles to the traditional BPD through the thalami, third ventricle, and cavum septum pellucidum) rather than transverse section through the fetal head. In 265 patients at 14 to 41 weeks' gestation, simultaneous measurement of the coronal and transverse BPDs revealed that they were interchangeable (r = 0.99). The major drawback of the coronal BPD is the inability to obtain a head circumference because of the absence of the occipitofrontal diameter. PMID- 2231854 TI - Sonographic appearance and ultrasound-guided fine-needle aspiration biopsy of breast carcinomas smaller than 1 cm3. AB - The purpose of this study was to review the sonographic appearance and the results of ultrasound-guided fine-needle aspiration biopsies of a series of 49 breast carcinomas smaller than 1 cm3. No tumor was found to be hyperechoic. Contours were irregular in 69% of cases. In 53%, an echogenic rim was present, and the echotexture was nonhomogeneous in 41%. Sound beam attenuation was present in 39%. The ratio of longitudinal diameter to anteroposterior diameter ranged from 0.67 to 2.25 (mean, 1.08 +/- 0.28). Fine-needle aspiration biopsy under continuous real-time sonographic guidance was performed on 36 patients and yielded 30 positive and four suspicious results (sensitivity, 94%), one inadequate specimen, and one false-negative result. With high-resolution hand held transducers, breast sonography can depict small carcinomas and provides accurate, cost-effective guidance for fine-needle aspiration biopsy. PMID- 2231855 TI - Sonographic imaging of the fetal azygous vein. Normal and pathologic appearance. AB - Sonologists should be familiar with the frequency of resolution and the ultrasonic appearance of the normal fetal azygous vein. In this study, 66 consecutive uncomplicated pregnancies were scanned to determine the frequency of imaging the fetal thoracic azygous vein. Between 21.7 and 30 gestational weeks, the azygous vein could be imaged in 50% of the cases and measured 1-2 mm in caliber. In the last 10 weeks of pregnancy, the azygous vein could be imaged in 98% of the cases and measured 2-4 mm. A case of fetal azygous continuation of the inferior vena cava is shown where the vein was abnormally dilated to a caliber of 8 mm. PMID- 2231856 TI - Device for the calibration of flow-velocity-measuring Doppler ultrasound equipment. AB - A new device is described for verifying the calibration accuracy of flow-velocity Doppler ultrasound (US) equipment. A rotating circular disk whose circumferential velocity may be fixed or modulated provides a strong signal source suitable for calibrating clinical Doppler US instruments. Circumferential edge velocity, derived from the disk angular frequency, is used to verify the accuracy of Doppler instrument calibration. A limited survey of routinely used Doppler US instruments demonstrates that calibration accuracy generally is satisfactory for clinical purposes, with minimal variation between instruments. Factors that affect measurements include transducer type, scale range, and display size. All transducers used on a specific piece of equipment need to be tested because the transducer design is an important part of the instrument operation. Variations were observed in reported velocities obtained from different transducers on the same equipment and for the same transducer with different scale ranges. In particular, some scales were more accurate than others, suggesting that individual scales should be tested when performing clinical Doppler US instrument calibration. Other measures of performance including scale display range, sample depth, aliasing, and transducer selection may be studied to identify their effect on measurement accuracy. Temporal modulation of angular velocity produces waveforms that may be used to simulate pulsatile velocity characteristics. The device is simple to construct and use, and it provides a convenient way to verify high-quality instrument performance. PMID- 2231857 TI - The biophysical profile. A literature review and reassessments of its usefulness in the evaluation of fetal well-being. AB - Antenatal monitoring studies to assess fetal well-being and to identify the compromised fetus are in widespread use. This literature review analyzes the theoretical basis for fetal monitoring and the clinical research that has defined its utility, and it discusses the variations in protocols and scoring systems for the biophysical profile. While recognizing that there, is as yet, no consensus on the optimal monitoring protocol, the authors espouse one approach in which the cardiac nonstress test and the amniotic fluid volume are the initial tests, with full biophysical profile reserved for abnormal test outcomes. This approach to monitoring should be expeditious without diminishing its predictive value. PMID- 2231858 TI - Cephalothoracopagus janiceps disymmetros twinning. PMID- 2231859 TI - Echocardiography in acute myocarditis associated with left ventricular thrombus formation and systemic embolization. PMID- 2231860 TI - Sonographic detection of a small-bowel bezoar. PMID- 2231861 TI - The snowflake sign. A sonographic marker for prenatal detection of fetal skin denudation. PMID- 2231862 TI - Inexpensive technique for hard copy demonstration of color flow data using gray scale format. PMID- 2231863 TI - First trimester conceptus. PMID- 2231864 TI - The benzimidazole anthelmintic agents--a review. PMID- 2231865 TI - Bovine mastitis--why does antibiotic therapy not always work? An overview. PMID- 2231866 TI - Contrasting effects of nitrofurans on plasma corticosterone in chickens following administration as a bolus or diet additive. AB - Administration of furazolidone as a bolus dose (8-500 mg/kg), produced a decrease in plasma corticosterone in chickens. In contrast, addition of furazolidone or furaltadone to the diet (0.04% or above, 10 days), increased plasma corticosterone. Pre-treatment with a 200-mg/kg bolus of furazolidone or furaltadone did not affect pentobarbitone anaesthesia time in the birds. In chickens pre-treated with a nitrofuran in the diet, however, pentobarbitone anaesthesia time was significantly less than that in controls. Furaltadone in the diet, produced significant increases in the amount of cytochrome P-450 and the activity of aniline hydroxylase in the liver microsomes. It is suggested that nitrofurans given in the diet stimulated corticosterone biosynthesis in the adrenal glands and induced mixed-function oxidase activity in the liver. Nitrofurans given as a bolus did not produce these effects. Furazolidone (200 mg/kg) produced severe anorexia, which lasted 2 days in T-line birds. The anorexia seemed to be associated with tissue damage in the birds rather than the ensuing adrenal cortical insufficiency. PMID- 2231867 TI - Tissue concentrations of clindamycin after multiple oral doses in normal cats. AB - Eighteen normal cats were randomly allocated into two blocks with three treatment groups and dosed orally with clindamycin aqueous solution for 10 days at a dosage rate of 5.5 mg/kg twice daily (Group 1), 11 mg/kg twice daily (Group 2), or 22 mg/kg once daily (Group 3). At the end of dosing, all cats were killed and tissues were taken for clindamycin concentration analysis. Clindamycin was extracted from tissues using solid-phase extraction columns followed by microbiological assay of clindamycin using a cylinder plate assay using M. luteus. Recovery from each tissue was determined by inoculating known concentrations of clindamycin into drug-naive tissues and comparing the observed concentration from the expected concentration. Confirmation that the bioassay detected clindamycin and not N-desmethylclindamycin, its active metabolite, was done using gas-chromatography-mass-spectrometry. Concentrations were highest in the lung, with tissue:serum ratios greater than 3 in all groups. Concentrations were higher in Group 3 than Group 1 (P less than 0.05). Only liver concentrations in Group 3 were statistically higher than in Group 2, although all tissues except bone marrow and CSF had numerically higher concentrations in Group 3 than Group 2. The tissue:serum ratio was greater than 1 in all tissues studied except bone, cerebrospinal fluid, brain, and skeletal muscle. PMID- 2231868 TI - Chronopharmacokinetics of theophylline in the cat. AB - Studies of theophylline pharmacokinetics in humans have shown that a higher peak concentration and area under the curve (AUC), with a shorter time to peak (tp) occur after a morning dose than after an evening dose. The purpose of this study was to determine whether theophylline pharmacokinetics in the cat were also influenced by the administration time of day. Theophylline was administered to six cats in a three-way cross-over study as a single dose of intravenous aminophylline and oral sustained-release theophylline (Slo-bid Gyrocaps and Theo Dur Tablets), between 08.00-09.00 h (Phase I) and 20.00-21.00 h (Phase II). Subjects were maintained on a 12-h light (08.00-20.00 h): 12-h dark cycle. Similar to the human studies, the tp was shorter following the morning dose. Conversely, however, the peak plasma theophylline concentrations achieved in these cats following intravenous aminophylline and oral Slo-bid were significantly higher following the evening dose. The AUC obtained for Theo-Dur was also significantly greater following the evening dose. No single pharmacokinetic parameter could account for the higher plasma concentrations achieved following the evening dose. PMID- 2231869 TI - The effects of ambient temperature on amikacin pharmacokinetics in gopher tortoises. AB - The pharmacokinetics of amikacin were compared in two groups of tortoises, one held at 20 degrees C and the other at 30 degrees C. The mean (+/- SD) residence time for amikacin in the 30 degrees C tortoises was 22.67 +/- 0.50 h; significantly (P less than 0.05) less than those held at 20 degrees C (41.83 +/- 3.23 h). There was no significant difference (P greater than 0.05) in the steady state volume of distribution (Vd(ss] between the tortoises held at 30 degrees C (0.241 +/- 0.520 l/kg) and those held at 20 degrees C (0.221 +/- 0.019 l/kg). The clearance rate was faster (P less than 0.05) in the warmer tortoises (10.65 +/- 2.42 ml/min/kg at 30 degrees C compared to 5.27 +/- 0.152 ml/min/kg at 20 degrees C). These data indicate that while the volume of distribution was approximately the same, amikacin remained in the colder tortoises longer because of its slower elimination. The oxygen consumption and metabolism were measured and found to be lower in the colder tortoises, almost by the same 2:1 ratio as clearance time (Cl), mean residence time (MRT), and area under the curve (AUC). The data derived from this limited study indicated that an appropriate therapeutic dosage regimen for amikacin in gopher tortoises at 30 degrees C is 5 mg/kg given i.m. every 48 h. PMID- 2231870 TI - The effects of dexamethasone, betamethasone, flunixin and phenylbutazone on bovine natural-killer-cell cytotoxicity. AB - A series of in-vitro experiments was performed utilizing the ability of bovine peripheral-blood mononuclear cells (PBMC) to induce lysis of Madin-Darby bovine kidney (MDBK) cells infected with bovine herpesvirus 1 (BHV1), in an antibody independent natural-killer(NK)-cell cytotoxic assay. The effects of dexamethasone (dexamethasone sodium phosphate), betamethasone (betamethasone sodium phosphate), flunixin (flunixin meglumine) and phenylbutazone on this NK cytolysis were studied using concentrations of the drugs ranging from well below to well above those normally attained in plasma at recommended therapeutic doses. All four drugs inhibited NK activity. For each agent a minimum inhibitory concentration (MIC50) required to inhibit NK activity by approximately 50% was calculated. For dexamethasone, betamethasone and flunixin the MIC50 was lower after a 24-h pre incubation of PBMC with each drug, although a marked inhibition was seen when the drug was only present during the 5-h NK assay itself. In contrast the MIC50 for phenylbutazone rose after a 24-h pre-incubation with PBMC. PMID- 2231871 TI - Comparative benzylpenicillin pharmacokinetics in the dromedary Camelus dromedarius and in sheep. AB - Benzylpenicillin pharmacokinetics were compared in the dromedary Camelus dromedarius (n = 5) and in sheep (n = 5) after administration of a single intravenous injection of benzylpenicillin. The data were described by an open three-compartment model with elimination from the central compartment. Body clearance (Clb) was 4.87 +/- 0.63 ml/min/kg in the dromedary and 9.17 +/- 1.39 ml/min/kg in sheep, the steady-state volumes of distribution (Vss) were 0.151 +/- 0.023 l/kg and 0.165 +/- 0.038 l/kg and the mean residence times (MRT) 27.34 +/- 1.38 min and 14.95 +/- 4.16 min in the dromedary and in sheep, respectively. It was concluded that benzylpenicillin elimination occurs more slowly in the dromedary than in sheep and that use of the same dosage regimen for the two ruminant species may lead to significant differences in plasma concentrations and therapeutic efficacy. PMID- 2231872 TI - Influence of feeding on the bioavailability of ronidazole prolonged-release formulations in pigeons. AB - The influence of feeding on the bioavailability of ronidazole (5 mg per animal) formulated as a hydrophilic-matrix tablet or as lipophilic pellets, was evaluated in pigeons. Administered to fed pigeons, prolonged drug absorption was obtained for both formulations. In non-fed pigeons an immediate grinding of the formulations in the gizzard resulted in rapid drug absorption. This indicates that prolonged residence of the prolonged-release formulations in the crop obtained in the fed condition seemed the only possible means of obtaining prolonged drug release in pigeons. PMID- 2231873 TI - Drug plasma levels following administration of trimethoprim and sulphonamide combinations to broilers. AB - Trimethoprim (TMP) was administered in combination with either sulphadiazine or sulphadimidine to broilers, and plasma concentrations were determined simultaneously by newly developed thin-layer and/or high-performance liquid chromatographic procedures, which also allowed quantification of the N4-acetyl metabolites of the sulphonamides. After i.v. injection of TMP (20 mg/kg body wt) and sulphadiazine (100 mg/kg body wt), both compounds were rapidly eliminated from plasma with half-lives of 1 and 2.7 h, respectively. Apparent volumes of distribution (3.3 and 0.96 l/kg, respectively) indicated that the tissue distribution of TMP was more extensive than that of the sulphonamide. After oral administration of the same dosages, elimination appeared to be slower compared to the i.v. injection, but this was obviously related to delayed absorption. Bioavailability after oral administration was approximately 100% of sulphadiazine, but only about 60% for TMP. Oral dosing of TMP in combination with sulphadimidine yielded similar maximum plasma concentrations of both compounds to those obtained with the combination of TMP with sulphadiazine, but the plasma concentration decline of sulphadimidine appeared to be more rapid than that of sulphadiazine after oral administration. During prolonged administration of different dosages of TMP-sulphadiazine combinations via drinking water, only low plasma concentrations were attained by the recommended dosage of the combination. Up to 10-fold higher dosages were tolerated by the animals without side-effects. In view of the fact that the sensitivity of bacterial strains to TMP-sulphonamide combinations differs widely, the plasma concentrations determined in the present study during prolonged drinking-water medication with different dosages of a TMP sulphadiazine combination can be used to select effective doses for treatment of different poultry diseases. PMID- 2231874 TI - The pharmacokinetics of oxytetracycline following intravenous administration in healthy and diseased pigs. AB - The pharmacokinetics of oxytetracycline (OTC) were studied in healthy pigs and in pigs endobronchially inoculated with Actinobacillus pleuropneumoniae toxins. In two groups of seven pigs OTC was administered intravenously in a single dose of 10 or 50 mg/kg, respectively. OTC was administered to clinically healthy pigs and 7 days later at 3 h after a challenge with A. pleuropneumoniae toxins. Pneumonia developed in toxin-treated pigs. In the challenged pigs there was a decreased distribution-rate constant (alpha) and a significantly increased elimination-rate constant (beta) (P less than 0.05). Moreover, the apparent volume of distribution (Vd beta) was decreased. The elimination half-lives (t1/2 beta) were approximately 6 h in the healthy pigs and 5 h in the diseased animals. There was no difference in the pharmacokinetic profile of OTC following administration of 50 mg/kg compared to 10 mg/kg. PMID- 2231875 TI - Effects of E. coli endotoxin, some interferon-inducers, recombinant interferon- alpha 2a and Trypanosoma brucei infection on feed intake in dwarf goats. PMID- 2231877 TI - Anatomical relationship between the renal venous arrangement and the kidney collecting system. AB - The anatomical relationships between the renal venous arrangement and the pelviocaliceal system were studied in 52, 3-dimensional polyester resin corrosion endocasts. In 53.8% of the cases, there were 3 large venous trunks and in 28.8% there were 2 venous trunks joining to form the main renal vein. Intrarenal veins demonstrated free anastomoses that were disposed in 3 systems of longitudinal arcades (stellate, arcuate and interlobar veins). There were large venous collars around caliceal necks and also horizontal arches crossing over calices to link anterior and posterior veins. In 84.6% of the cases the upper caliceal group was encircled anteriorly and posteriorly by venous plexuses, which coursed parallel to the infundibulum. In 50.0% of the cases the lower caliceal group also was enriched by 2 venous plexuses. A close relationship existed between a large inferior tributary of the renal vein and the anterior aspect of the ureteropelvic junction in 40.4% of the cases. In 69.2% of the cases there was a posterior (retropelvic) vein: in 48.1% this vein had a close relationship to the junction of the pelvis with the upper calix and in 21.1% it crossed the middle posterior surface of the renal pelvis. PMID- 2231876 TI - Neoadjuvant chemotherapy in invasive bladder cancer: the evolving role of surgery. AB - The role of an operation in patients receiving neoadjuvant chemotherapy for clinically localized but invasive transitional cell carcinoma of the bladder currently is evolving. An operation is essential for case selection and evaluation of local response but it also contributes to bladder preservation and survival. The procedure that is necessary to select for and assess response to chemotherapy may itself alter the actual or proceed to evolution of invasive bladder cancer. Neoadjuvant chemotherapy is a reasonable therapeutic strategy in selected patients but it remains to be seen whether the results will prove to be superior to those achieved with standard endoscopic and open operations. PMID- 2231878 TI - Incidence and properties of renal masses and asymptomatic renal cell carcinoma detected by abdominal ultrasonography. AB - Renal ultrasonography was performed in 45,905 adults, including 41,364 without any signs suggesting urinary tract malignancies, 1,667 with microscopic hematuria only and 2,874 with some signs of malignancy. Renal lesions were found in 355 adults (0.858%) in the asymptomatic, 39 (2.3%) in the microscopic hematuria and 75 (2.6%) in the symptomatic groups, respectively. Renal cell carcinoma was found in 35 (7.5%) lesions: 19 (5.4%) in the asymptomatic, none in the microscopic hematuria and 16 (21.3%) in the symptomatic groups. A total of 47 patients, including 12 other renal cell carcinoma patients transferred from related hospitals, was grouped into 28 without and 19 with symptoms. Primary tumor size and clinical stages were significantly smaller and lower, respectively, in the asymptomatic group than in the symptomatic group. Radical nephrectomy was performed in all but 2 asymptomatic patients. The 5-year survival rates after nephrectomy were 94.7 and 60.9% for the asymptomatic and symptomatic groups, respectively (p less than 0.01). The results indicate that ultrasonography is a useful tool to detect low stage asymptomatic renal cell carcinoma at low cost. PMID- 2231879 TI - Magnetic resonance imaging for assessment of vena caval tumor thrombi: a comparative study with venacavography and computerized tomography scanning. AB - We assessed the accuracy of magnetic resonance imaging in demonstrating the presence and extent of vena caval tumor thrombi. The study group included 20 patients with vena caval thrombi from renal cell carcinoma (18), renal pelvic transitional cell carcinoma (1) and adrenal pheochromocytoma (1). Preoperative diagnostic studies included magnetic resonance imaging in all patients, inferior venacavography in 16 and computerized tomography scanning in 15. All patients underwent an operation in which the presence and extent of the vena caval thrombus were confirmed. Magnetic resonance imaging accurately delineated the presence and extent of the thrombus in all 20 patients (100%). Venacavography was accurate in 15 patients (94%) but 8 (50%) required a retrograde and antegrade study. Computerized tomography scanning demonstrated the presence of a tumor thrombus in all 15 patients but accurately delineated the cephalad extent of the thrombus in only 5 (33%). In patients with vena caval tumor thrombi magnetic resonance imaging can provide accurate information regarding the extent of vena caval involvement while avoiding the need for an invasive contrast imaging study. PMID- 2231881 TI - Ureterosigmoidostomy: long-term results, risk of carcinoma and etiological factors for carcinogenesis. AB - We followed postoperatively 75 patients who underwent ureterosigmoidostomy between 1942 and 1987. Of the patients 30 were asked to undergo routine examination, including fiberoptic sigmoidoscopy with biopsy and analysis of a urine-feces slurry for nitrate, nitrite and nitrosamines in comparison to 20 control volunteers. After a mean observation of 14 years 7 months (1 to 46 years) 64.5% of the patients had bilaterally normal kidneys without any previous complications, 77.5% of the renal units being normal. Sigmoidoscopic biopsy revealed 3 carcinomas at the ureterocolonic junction resulting in an 8.5 to 10.5 fold increased risk of colon carcinoma compared to the general population. The excretion of nitrite and N-nitrosamines was increased, and nitrate excretion was decreased compared to healthy control volunteers, suggesting endogenous formation of nitrosamines by bacterially reduced nitrate and endogenous amines. The urological long-term results of ureterosigmoidostomy are similar to those of conduits. However, the increased incidence of colon carcinoma is not yet proved to be higher than in conduits. PMID- 2231880 TI - Extravesical versus Leadbetter-Politano ureteroneocystostomy: a comparison of urological complications in 320 renal transplants. AB - The urological complications of 320 consecutive renal transplants performed at our institution between October 17, 1985 and November 10, 1989 are reviewed. The Leadbetter-Politano technique of ureteroneocystostomy was used in the first 160 patients (group 1) and an anterior extravesical technique modified from the methods of Witzel, Sampson and Lich was performed in the second 160 patients (group 2). Urological complications occurred in 15 patients (9.4%) in group 1 and 6 (3.7%) in group 2 (p = 0.04). Ureterovesical junction obstruction occurred in 6 patients (3.7%) in group 1 and 1 (0.6%) in group 2 (p = 0.05). Complications of leakage, ureteral necrosis and ureteral stricture were comparable in the 2 groups. Therefore, we advocate the use of the anterior extravesical technique over Leadbetter-Politano ureteral reimplantation based on the lower incidence of urological complications and various technical advantages, including less operative time, avoidance of a separate cystotomy, less hematuria and ability to use short donor ureters. PMID- 2231882 TI - Primary adenocarcinoma of the bladder: favorable prognostic significance of deoxyribonucleic acid diploidy measured by flow cytometry. AB - Flow cytometric nuclear deoxyribonucleic acid ploidy analysis was done successfully on 38 specimens of primary bladder adenocarcinoma treated between 1954 and 1985. Of the specimens 10 (26%) were deoxyribonucleic acid diploid, 8 (21%) were tetraploid and 20 (53%) were aneuploid. Distribution of ploidy patterns between the 14 histological low grade and 24 high grade tumors was similar. Of 38 tumors 35 (92%) showed muscle invasion. One tumor arose in a previously exstrophied bladder, 10 were of urachal origin and 27 arose in an anatomically normal bladder. Of the urachal origin tumors 80% were deoxyribonucleic acid aneuploid. At 5 and 10 years after diagnosis 80 and 70%, respectively, of the patients with diploid tumors were free of disease. By contrast, at 5 and 10 years after treatment only 20 and 12%, respectively, of the patients with nondiploid tumors have not had disease progression (p less than 0.001 log-rank test). None of the 6 patients with diploid, high grade, high stage, muscle invasive tumors had subsequent progression. In contrast, 16 of 17 patients (94%) with high grade, high stage, nondiploid tumors had either local or distant tumor recurrence (p less than 0.0005). Nuclear deoxyribonucleic acid ploidy pattern appears to be the most significant prognostic information currently available to stratify expected prognosis for patients with muscle invasive adenocarcinoma of the bladder. This test probably should be a standard tool in the clinical management of patients with this rare bladder malignancy. PMID- 2231884 TI - Perioperative methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) for poor risk transitional cell carcinoma of the bladder: an Eastern Cooperative Oncology Group pilot study. AB - A total of 18 patients with locally advanced transitional cell carcinoma of the bladder underwent 2 preoperative cycles of chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin followed by radical cystectomy and 2 postoperative cycles of chemotherapy. Radical cystectomy was performed in 17 of 18 patients (94%) with a pathological partial response in 3 (17%) and a pathological complete response in 2 (11%), for an over-all response rate of 28% (95% confidence limits 10 to 53%). At 23-month median followup 9 patients (50%) remained without evidence of recurrent disease, while 9 (50%) died of metastatic bladder cancer. Average relative dose intensity of all therapy given was 78%. Hematological toxicity was moderate, with no septic deaths or bleeding complications. However, 4 thromboembolic events occurred. While downstaging of the primary bladder tumor can occur with this perioperative schedule our results were not as impressive as some previously reported findings. The incidence of thromboembolic events is worrisome. PMID- 2231883 TI - Randomized phase II evaluation of carboplatin and CHIP in advanced transitional cell carcinoma of the urothelium. The Eastern Cooperative Oncology Group. AB - A total of 83 patients with metastatic transitional cell carcinoma who had previously received no systemic therapy entered a randomized phase II evaluation of carboplatin and cis-dichloro-transdihydroxy-bis-isopropylamine platinum IV (CHIP), administered respectively at 400 and 270 mg./m.2 every 28 days. Among evaluable patients with measurable disease response rates were 3 of 22 (14%, 95% confidence interval 5 to 35%) for carboplatin and 4 of 25 (16%, 95% confidence interval 5 to 36%) for CHIP. Among 17 patients with evaluable but not measurable metastases (10 carboplatin and 7 CHIP recipients) there were no responses. Median survival for 64 evaluable patients was 4.8 months (5.0 months for carboplatin and 4.3 months for CHIP recipients). Independent factors prognostic for survival (p less than 0.01) were performance status (0 or 1 versus 2 or 3), liver metastases, prior radiation therapy and recent weight loss (p = 0.02). Multivariate analysis confirmed that a performance status of 2 or 3 and liver metastases were predictive of shorter survival. A total of 31% of the patients treated with carboplatin and 34% of those who received CHIP experienced severe or life threatening myelosuppression. While the response rates with carboplatin and CHIP are modest, we believe that the characteristics of these agents indicate that they should be evaluated further. PMID- 2231885 TI - Local recurrence and survival following nerve-sparing radical cystoprostatectomy. AB - From March 1982 through July 1988, 76 men underwent nerve-sparing radical cystoprostatectomy for carcinoma of the bladder at our hospital. Of the 76 patients 2 (2.6%) had positive surgical margins (dome of the bladder and left ureter) and neither had positive margins at the site of nerve-sparing modifications. Of 3 patients (3.9%) who had local recurrence none had positive surgical margins. The 5-year actuarial local recurrence rate is 7.5%. Thirteen of 76 patients (17%) died of transitional cell carcinoma and 7 (9%) died of other causes, while 53 (70%) are alive without evidence of disease with a mean followup of 38.4 months. The 5-year actuarial survival rates are 64% over-all, 68% without disease and 78% disease-specific. Of the 42 evaluable men who underwent cystoprostatectomy alone 27 (64%) are potent, compared to 2 of the 12 men (17%) who also underwent urethrectomy. We conclude that the nerve-sparing modifications do not compromise cancer control, that local recurrence and survival rates are at least comparable to those achieved with standard radical cystoprostatectomy, and that it is possible to preserve potency in most men undergoing this procedure. PMID- 2231886 TI - Recurrent urethral stricture disease managed by clean intermittent self catheterization. AB - We studied 41 patients with urethral stricture who had failed at least 1 operation, and were being maintained with filiform and follower dilation every 6 to 12 weeks. The patients were instructed in clean intermittent self catheterization with a 16F red rubber catheter, which was performed every 1 to 30 days. Followup from 9 to 36 months revealed excellent compliance and average peak uroflow rates increased from 5.5 cc per second before dilation to 17.1 cc per second at the last followup visit. Clean intermittent self-catheterization is a simple method to maintain a patent urethra and obviates the need for further operations or painful dilations. PMID- 2231887 TI - The microarchitecture of the intracavernosal smooth muscle and the cavernosal fibrous skeleton. AB - The bulk of the parenchyma of the corpora cavernosa consists of bundles of smooth muscle fibers. These bundles are oriented in all directions and establish at least 2 insertions upon elements of the fibrous skeleton of the corpora. The fibrous skeleton includes the tunica albuginea and its fibrous columns, the intracavernous fibrous framework, and the periarterial and perineural fibrous sheaths. The cavernous vascular spaces (sinusoids) form an intercommunicating network embedded within the mass of smooth muscle. Thus, the smooth muscle does not form a muscular wall proper for each sinusoid. PMID- 2231888 TI - Arteriographically determined occlusive disease within the hypogastric-cavernous bed in impotent patients following blunt perineal and pelvic trauma. AB - To determine the presence, location and pattern of arterial occlusive disease within the hypogastric-cavernous arterial bed in impotent men following blunt perineal and pelvic trauma, we reviewed the selective internal pudendal arteriograms of 20 patients with a history of blunt perineal and 7 with blunt pelvic trauma who had immediate development of impotence. Arteriographic studies of 104 other impotent patients also were reviewed and compared. Patients with persistent impotence immediately after blunt pelvic and perineal trauma had significantly different patterns of arteriographically demonstrated occlusive disease within the distal hypogastric-cavernous arterial bed consistent with the site of the traumatic injury. Those who sustained blunt pelvic trauma and complained of immediate impotence revealed arterial occlusive lesions mainly in the internal pudendal, common penile, cavernous and dorsal arteries. The incidence of arterial lesions in the distal internal pudendal or common penile artery was significantly higher (p less than 0.01) in patients with blunt pelvic trauma (92%) than in those with blunt perineal trauma (35%). Patients who sustained blunt perineal trauma and complained of immediate impotence demonstrated a more focal pattern of pathological arterial occlusion primarily in the cavernous and dorsal arteries. The incidence of a solitary arterial lesion in the cavernous artery without proximal disease was significantly higher (p less than 0.05) in patients with blunt perineal trauma (48%) than in those with blunt pelvic trauma (8%). It is hypothesized that blunt trauma without immediate impotence may be a potential risk factor for later development of arterial vasculogenic impotence, and that unrecognized or seemingly innocuous trauma may be a factor in cases of idiopathic impotence. Patients without trauma and with vascular risk factors have a more diffuse pattern of arteriographically demonstrated arterial lesions. PMID- 2231889 TI - Patient acceptance of and satisfaction with an external negative pressure device for impotence. AB - Patient acceptance of and satisfaction with an external negative pressure device as a treatment for impotence were retrospectively analyzed among 100 men. The over-all satisfaction rate was 68%. Reasons for dissatisfaction with and discontinuing the use of the device included premature loss of penile tumescence and rigidity, pain or discomfort either during application of suction or during intercourse and inconvenience. Negative pressure therapy is an effective treatment for impotence of various etiologies and should be among treatment options offered to the impotent patient. PMID- 2231891 TI - Radical prostatectomy for clinical stage T1-2N0M0 prostatic adenocarcinoma: long term results. AB - A total of 441 stage T1-2N0M0 and 11 stage T1-2N0M0 cancer patients with an elevated acid phosphatase level only, and 18 stage T1-2N+M0 cancer patients underwent radical prostatectomy. Analysis of the 441 stage T1-2N0M0 cancer patients demonstrated that failure and survival were a function of the disease being organ-confined, specimen-confined or margin-positive, with 10-year failure rates of 12, 30 and 60%, respectively. Of the patients with positive margins 44 were and 79 were not irradiated postoperatively. Postoperative radiation produced no survival advantage. No difference in interval to failure or of survival could be identified between 105 patients whose disease was diagnosed by transurethral resection and 328 who had a palpable abnormality. Eleven patients had negative bone and node findings but they had an elevated acid phosphatase level. All 8 patients not treated with immediate androgen deprivation failed within 36 months. PMID- 2231890 TI - Testicular carcinoma in patients positive and at risk for human immunodeficiency virus. AB - Patients with the acquired immunodeficiency syndrome are at increased risk for certain malignancies. Because acquired immunodeficiency syndrome and testicular cancer affect primarily young men, the potential complications that acquired immunodeficiency syndrome might impose raise significant concern. To address this question we performed a retrospective review of all cases of testicular cancer during an 11-year period. Of 140 patients 6 had human immunodeficiency virus infection and 7 were from human immunodeficiency virus risk groups. All cases were either stage I or II disease with seminoma in 8, teratocarcinoma in 3, embryonal cell carcinoma in 1 and teratoma in 1. The clinical presentations of these patients were comparable to those of patients without human immunodeficiency virus risk factors. The majority of the patients received standard therapy, including orchiectomy followed by lymphadenectomy, radiation therapy or chemotherapy depending on stage and pathological subtype. Patients tolerated therapy well with only 1 course of radiation therapy complicated by Pneumocystis carinii pneumonia. All patients achieved complete remission and none died of testicular cancer. Since treatment of these patients may worsen the immunosuppression, surveillance is recommended after orchiectomy for acquired immunodeficiency syndrome patients with stage I disease. However, the majority of patients with human immunodeficiency virus infection should receive standard therapy. PMID- 2231892 TI - Improved technique for creation of ileal conduit stoma. AB - Creation of a circumferentially protruding urinary intestinal stoma is an important aspect to prevent stomal regression, stenosis and parastomal herniation. Furthermore, an improperly fashioned stoma may make fitting of an ostomy appliance difficult, resulting in urinary leakage with secondary dermatitis and incrustation. The major difficulty in fashioning the stoma is everting the mucosa over the intestinal mesentery. We describe our method of stoma formation that creates a circumferentially symmetrical protruding stoma free of tension that has been used successfully even in obese patients. This technique has made the use of a Turnbull stoma unnecessary in our recent experience. PMID- 2231893 TI - A new technique for ileal nipple fixation: preliminary report. AB - A new technique for ileal nipple fixation is described in 6 post-cystectomy patients (4 with an ileal bladder substitute and 2 with an ileal reservoir) for the prevention of reflux. Nipple formation is helped by deperitonealization and defatting of the nipple mesentery. A full circumferential incision is made, except for the mesenteric border, and through both nipple layers down to the mucosa of the inner layer. The seromuscular layers on each side of the incision are closed together with continuous 3-zero polyglycolic acid suture. The overlying outer mucosa of both edges then is closed. Endoscopic and radiographic study 6 to 12 months postoperatively showed a stable nipple without reflux. The anatomical and physiological rationale of the technique is discussed. PMID- 2231894 TI - Mohan's urethral valvotome: a new instrument. AB - Electrothermic fulguration of posterior urethral valves with a resectoscope is difficult in newborns, especially in small for gestation date and premature newborns because of a small caliber urethra. This difficulty has prompted the innovation of the valvotome described. The outer diameter of the valvotome is 3 mm. and it can be easily introduced without stretching the urethra. This instrument has been used successfully in 8 patients to date. Patient age ranged from 3 days to 3 1/2 years with varying degrees of hydronephrosis and hydroureter. All patients have a good urinary stream with regression of the hydronephrosis and hydroureter. PMID- 2231895 TI - The urethral plug: a new treatment modality for genuine urinary stress incontinence in women. AB - A new modality, the urethral plug, was used to treat 22 women with genuine urinary stress incontinence. The plug is made of thermoplastic elastomer (Kraton G), and consists of a meatal plate, a soft stalk and 1 or 2 spheres along the stalk. The spheres were located according to the result of the urethral pressure profile. The midpoint of the proximal sphere was placed at the bladder neck and the distal sphere was placed just above the maximum urethral pressure point. At voiding the plug was removed and afterwards a new plug was inserted. The plug with 2 spheres was tested in week 1 (period 1) and the plug with only the distal sphere was tested in week 2 (period 2). A total of 22 patients completed period 1. Eight patients did not complete period 2, mostly due to either unchanged incontinence during period 1 or a repeated loss of the plug with 1 sphere. In periods 1 and 2, 73 and 79% of the patients were subjectively and objectively continent or improved. A total of 14 patients completed both periods. Eight patients preferred the plug with 2 spheres, 1 preferred the other plug and 5 had no preference. The side effects were few. This preliminary study shows that the urethral plug seems to be a promising alternative treatment for female genuine urinary stress incontinence. PMID- 2231896 TI - Uncircumcision: a technique for plastic reconstruction of a prepuce after circumcision. AB - A simple technique is described for plastic reconstruction of the prepuce. Penile skin is used and the defect created is covered by implantation of the penis into the scrotum. At a second stage the penis is released from the scrotum. PMID- 2231897 TI - Urinary retention due to sacral myeloradiculitis: a clinical and neurophysiological study. AB - We report 5 cases of sacral myeloradiculitis presenting with transient urinary retention. Neurophysiological testing, including bulbocavernosus reflex, pudendal evoked response and external anal sphincter electromyography, was performed. Parasympathetic pelvic nerves, pudendal nerves as well as the spinal cord seem to be involved to various degrees in this infrequent disorder. PMID- 2231898 TI - Long-term urinary continence and renal function in neonates with posterior urethral valves. AB - Posterior urethral valves are known to be associated with considerable morbidity and mortality especially in the neonate. Recently the role of bladder dysfunction in the pathophysiology of renal function impairment and urinary incontinence after valve ablation has been questioned. From 1976 to 1986 we treated 50 male newborns with posterior urethral valves at our institution. Initial treatment in all cases consisted of bladder drainage by a urethral catheter, and correction of existing fluid and electrolyte abnormalities. Subsequent treatment was dictated by the degree of upper tract abnormalities and it included valve ablation alone in 24 patients, vesicostomy and later valve ablation in 8, valve ablation and later upper tract reconstruction in 14 and cutaneous ureterostomy in 4. Followup ranges from 2 to 12 years (mean 6.8). Long-term renal functional impairment was related to the serum creatinine at age 1 year. If the serum creatinine was below 1.0 mg.% all patients (31) had normal values at long-term followup and if it was greater than 1.0 mg.% (19) then only 7 patients had normal values at followup. Urinary continence was assessed in 42 patients and it was normal in 34 (81%). The etiology of incontinence in the remaining 8 patients was bladder dysfunction in 6 and sphincter incompetence in 2. Those patients with urinary incontinence also had a high incidence of upper tract abnormalities (6 of 8, 75%) compared to continent valve patients (10 of 34, 29%). PMID- 2231899 TI - The management of posterior urethral valves by initial vesicostomy and delayed valve ablation. AB - We managed 32 neonates and infants with temporary vesicostomy and delayed valve ablation. The criterion on which successful management was gauged was estimated creatinine clearance. Renal failure or death occurred in 30% of the patients and 7% required transplantation. There was no apparent difference between our patients managed initially with vesicostomy and other series managed initially with valve ablation in preventing the complications of posterior urethral valves. PMID- 2231900 TI - Pheochromocytoma in the pediatric age group: the prostate--an unusual location. AB - Pheochromocytomas of the prostate are rare, with only 3 cases in adults reported in the literature. We present the case of an 8-year-old boy with a pheochromocytoma of the prostate and a second tumor in the region of the left internal iliac artery. PMID- 2231901 TI - Nuclear morphometry as a prognostic indicator for genitourinary rhabdomyosarcoma: a preliminary investigation. AB - Rhabdomyosarcoma of the urogenital tract is a malignant mesenchymal tumor seen primarily in childhood. Multimodal therapy, encompassing surgery, radiotherapy and chemotherapy, has dramatically improved the survival of patients with this disease. However, the quest for markers of tumor aggression is important to decrease the morbidity of treatment given to patients with good prognosis tumors, while at the same time intensifying treatment of tumors with poor prognosis. Using archival tumor specimens from 13 patients with genitourinary rhabdomyosarcoma, a multivariate analysis of multiple nuclear shape descriptors was done with the Hopkins Morphometry System. Three nuclear shape descriptors clearly separated patients with no evidence of disease recurrence or progression from those with recurrent disease, progressive disease or death of disease. These nuclear shape descriptors were standard error of the chain code standard deviation analysis (p = 0.010), range of the feret ellipticity distribution (p = 0.016) and standard error of the chain code range analysis (p = 0.037). With multivariate analysis these shape descriptors taken together separated patients with good and poor prognoses to a level of significance of p = 0.007. Thus, nuclear morphometric analysis may prove to be useful as an individual prognostic indicator in childhood genitourinary rhabdomyosarcoma and warrants further analysis in a much larger, blinded, controlled study. PMID- 2231903 TI - Massive hemorrhage from an arterioureteral fistula associated with chronic renal transplant failure. AB - A case of arterioureteral fistula from the graft artery stump of a failed transplant and the native ureter is reported. This case illustrates one of the possible complications of graft anastomosis. The etiological factors involved in the formation of the aneurysm and eventually the fistula are discussed. PMID- 2231902 TI - Embolization of a giant renal arterial aneurysm. AB - A 49-year-old man presented with right flank pain. Angiography revealed a giant right renal arterial aneurysm. Giant renal arterial aneurysms are typically treated by nephrectomy. In this patient the aneurysm was embolized successfully with multiple Gianturco-Wallace coils and polyvinyl alcohol. This case indicates that embolization may be a reasonable alternative to nephrectomy. PMID- 2231904 TI - Cyclophosphamide-induced hemorrhagic pyelitis and ureteritis associated with cystitis in marrow transplantation. AB - A 29-year-old woman suffered fatal hemorrhagic pyelitis, ureteritis and cystitis after receiving 4,800 mg./m.2 cyclophosphamide in preparation for marrow transplantation despite intravenous hydration and a Foley catheter. Cyclophosphamide-induced urothelial damage is not limited to the bladder and upper tract monitoring also is necessary. PMID- 2231905 TI - De novo carcinoma of the lower urinary tract in renal allograft recipients. AB - Immunocompetence has been postulated as an important defense against the progression of urothelial carcinoma. Three cases of de novo lower urinary tract carcinoma in renal transplant recipients demonstrated the potential for unusually rapid urothelial extension and invasion in chronically immunosuppressed patients. Two patients had a history of perineal condyloma acuminata; tumors from 1 of these harbored the genetic sequences of human papillomavirus type 6. One patient had multiple manifestations of cyclophosphamide-related urothelial injury, including bladder carcinoma. Treatment of 2 patients culminated in a radical operation during which the remaining native urinary system was resected completely, with sacrifice of the allograft kidney in 1 and diversion into an ileal conduit in 1. The remaining patient underwent urethrectomy and partial cystectomy with a sigmoid conduit. PMID- 2231906 TI - Burkitt's lymphoma of the testicle: report of 2 cases occurring in elderly patients. AB - Burkitt's lymphoma is rare in patients older than 50 years and almost never presents as a testicular tumor. We report 2 cases of primary Burkitt's lymphoma of the testicle in men 68 and 79 years old. In 1 man the extragonadal tumor had a rapid and lasting response to combination chemotherapy. The cases are of interest for the unusual presentation of the disease and for the possibility to control Burkitt's lymphoma in older patients without undue toxicity. The management of testicular lymphoma requires radical orchiectomy and prophylactic irradiation of the contralateral testis. Chemotherapy is indicated for advanced disease and may prevent relapses in patients with early disease. The role of central nervous system prophylaxis is controversial. PMID- 2231907 TI - Retroperitoneal lymph node dissection in malignant mesothelioma of tunica vaginalis testis. AB - A case of metastatic mesothelioma of the tunica vaginalis testis in a 57-year-old man is reported. Clinicopathological findings and treatment options are reviewed. PMID- 2231908 TI - Re: Adrenal hemorrhage in the newborn with evidence of bleeding in utero. PMID- 2231909 TI - Re: Prostatic needle biopsy: a simple technique for increasing accuracy. PMID- 2231910 TI - This month in Investigative Urology: the production of lymphokines following BCG therapy. PMID- 2231911 TI - Synchronized electrical stimulation of the sympathetic and parasympathetic innervation of the bladder: facilitation of the initiation of micturition in the dog. AB - To improve the quality of bladder contractions induced by parasympathetic stimulation and to facilitate the initiation of voiding, we investigated the effect of sympathetic stimulation on the parasympathetic innervation of the bladder in 12 dogs. For the sympathetic system, the lumbar sympathetic trunks were electrically stimulated; for the parasympathetic system, either the pelvic nerve or the ventral root of S2 was stimulated. With voltages at or just above the threshold for achieving a measurable effect on bladder pressure, stimulation of the sympathetic system or the pelvic nerve alone did not lead to voiding, and sacral root stimulation alone elicited voiding in only 7.4 per cent of stimulations. However, when the same stimulus parameters were used for synchronous stimulation, the voiding process was facilitated when sympathetic stimulation was begun five to 10 seconds before parasympathetic stimulation. When the pelvic nerve was used, voiding resulted in 77.7 per cent of stimulations and the bladder was emptied by a mean of 68.7 per cent; with S2 ventral root stimulation, voiding resulted in 83.3 per cent of stimulations and the bladder was emptied by 59.7 per cent. The facilitory effect of sympathetic stimulation was not abolished when the sympathetic trunks were cut centrally to the point of stimulation, but was absent when the hypogastric nerves were transected. We feel that sympathetic stimulation modulates the parasympathetic innervation of the bladder. PMID- 2231912 TI - Mechanical properties of the urethra in healthy and stress incontinent females: dynamic measurements in the resting urethra. AB - The relationship between pressure and cross-sectional area in the resting urethra during its inflation and deflation was examined in 30 healthy females and in 30 patients with genuine stress incontinence (GSI). Measurements were performed at the bladder neck, in the high-pressure zone and distally in the urethra. The mechanical properties of the urethra were found to vary significantly as a function of time after induction of a cross-sectional area (stress episode) in both groups of women. The pattern of response of the urethra showed significant differences between normals and GSI particularly during dynamic conditions. Our results indicate that mechanical laxity of the urethra at the bladder neck and midurethrally especially at dynamic events (stress episodes) is of pathophysiological importance in GSI. PMID- 2231914 TI - Long term effects of gastrocystoplasty in rats. AB - Twenty prepubescent rats underwent microsurgical gastrocystoplasty by a technique which is described. An equal number of control rats had their bladders opened and closed. Rats were sacrificed at 16 to 18 months postoperatively. There were no differences in final weight, serum electrolytes, or renal function between the two groups. Prominent histopathologic changes of the bladder occurred in the gastrocystoplasty group. These changes included papillomas present in five of the 15 rats surviving long term. No significant changes occurred in the bladders of the control group of rats. Possible etiologies and the significance of the rats. Possible etiologies and the significance of the gastrocystoplasty related lesions are discussed. PMID- 2231913 TI - Time-course of alterations of bladder function following acetone-induced cystitis. AB - Although chemical cystitis is known clinically to cause decreased bladder function, there are few experimental studies on the progression of, and recovery from chemical cystitis. Mature male rabbits underwent intravesical instillation of 50% acetone solution through a urethral catheter. Micturition profiles showed a marked decrease of the mean and maximal micturition volume and an increase in number of micturitions as early as one day after treatment. The micturition profile gradually normalized between four and eight weeks after instillation. In vivo cystometry showed a very small bladder capacity and low compliance during the first week following instillation, and gradually recovered to control levels by four weeks. Functional studies using the in vitro whole bladder model showed a significant decrease in the ability of the bladder to generate pressure and to empty at three days after instillation. These parameters recovered partially by two weeks, and completely by four weeks. Chemical cystitis induced by intravesical acetone instillation resulted in a severe decrease in the bladder function, i.e. contracted bladder with low compliance and poor ability to generate pressure and empty. However, these changes were reversible within the two month period of study. PMID- 2231915 TI - Comparison of antigen expression on normal urothelial cells in tissue section and tissue culture. AB - Antigenic characterization of urothelial cells cultured from normal adult ureter was performed. These cells were cultured using a simplified isolation and culture technique and a commercially available serum-free medium. The cells growing in these cultures had epithelioid morphology and normal quantities of DNA. The antigen expression on these cultured normal urothelial cells was evaluated using a panel of monoclonal antibodies: 5G6.4, AN43, URO-5, anti-keratin and anti-blood group antibodies, and 425 (anti-epidermal growth factor receptor). Lower levels of anti-A and AN43 binding on cultured cells were observed than are seen on urothelial cells in sections of normal ureter, while the binding of anti-blood group H, 5G6.4, and URO-5 was unchanged. Binding of anti-epidermal growth factor receptor antibody 425 was improved if the cells were grown in medium lacking epidermal growth factor. These results confirm the urothelial origin of these cultured urothelial cells but indicate that some antigenic differences between cultured normal urothelial cells and urothelial cells in situ in the normal ureter exist. PMID- 2231916 TI - Hyperfiltration-induced renal injury in normal man: myth or reality. AB - Current knowledge fails to support the notion that adaptive hyperfiltration of the remnant kidney after donor nephrectomy is deleterious. Rather than being maladaptive, hyperfiltration appropriately compensates for the loss of functional renal mass. Accordingly, most kidney donors can be expected to maintain a stable level of renal function without proteinuria or hypertension. Essential to this is proper selection of donors for nephrectomy and exclusion of high risk potential donors, bearing in mind the fact that apparently healthy, asymptomatic relatives of end stage renal disease patients are prone to the same disease processes that inflict the general population and have a higher risk of underlying renal disease. PMID- 2231917 TI - Fatal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer. AB - Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer. Complications from bacillus Calmette-Guerin therapy are usually minor but serious and even fatal reactions can occur. Five recent cases illustrate the gravity of bacillus Calmette-Guerin sepsis. One man with severe debility and the organic brain syndrome died acutely with a fever of 40 C. Two men had frank sepsis that progressed to multiorgan failure and death. Sepsis progressed despite the use of isoniazid, rifampin and streptomycin. Two men who had equally progressive sepsis with intravesical bacillus Calmette-Guerin survived with the use of cycloserine for the first 72 hours of treatment. Triple antituberculous antibiotics, including cycloserine, may be lifesaving. Sepsis resulted from intravenous absorption through inflamed or disrupted urothelium. Bacillus Calmette-Guerin treatment should not be administered in the presence of severe cystitis or after grossly traumatic catheterization. PMID- 2231919 TI - 3-dimensional imaging of the pelviocaliceal system by computerized tomographic reconstruction. AB - Safe and efficient performance of percutaneous nephrolithotomy requires 3 dimensional visualization of the pelviocaliceal anatomy. However, currently available modalities offer only 2-dimensional images, from which the operator must mentally reconstruct a 3-dimensional picture of the pelviocaliceal configuration. We evaluated the feasibility of obtaining 3-dimensional images of the pelviocaliceal system with the aid of computerized tomographic reconstruction and present 3 illustrative cases. PMID- 2231918 TI - Fatal disseminated mycobacterial infection following intravesical bacillus Calmette-Guerin. AB - We describe a fatal case of disseminated mycobacteriosis after intravesical bacillus Calmette-Guerin immunotherapy. We summarize the prior safety record of this therapeutic modality, discuss local and systemic pathophysiological mechanisms by which dissemination might have occurred, and review the reported clinical experience with antituberculous chemotherapy for significant bacillus Calmette-Guerin infection. Finally, we offer suggestions for prophylaxis of certain patients with a history of exposure to intravesical bacillus Calmette Guerin. PMID- 2231920 TI - Triamterene nephrolithiasis: renewed attention is warranted. AB - Although triamterene has been known to contribute to urinary calculus formation, it has been presumed to be a rare phenomenon. Our review of stone analyses performed during the last decade by a single laboratory reveals an increasing incidence of triamterene stones. Awareness of the calculogenic potential of triamterene-containing medications should be re-emphasized. PMID- 2231921 TI - Prospective comparison of plain abdominal radiography with conventional and digital renal tomography in assessing renal extracorporeal shock wave lithotripsy patients. AB - Most publications citing the effectiveness of renal extracorporeal shock wave lithotripsy have used plain abdominal radiography to assess residual calculi after treatment. We compared radiologist sensitivity and specificity in the detection of calculi on plain abdominal radiographs versus conventional film screen and digital renal tomograms in extracorporeal shock wave lithotripsy patients. Of the patients 50 were imaged before and within 24 hours after lithotripsy. Six radiologists evaluated the resultant 300 studies for the presence and location of calculi. The mean sensitivity for digital tomograms was 83% for pre-lithotripsy and post-lithotripsy studies, which was significantly higher than for plain abdominal radiography and conventional tomography after lithotripsy. However, there were significantly more false positive stone diagnoses associated with digital tomogram interpretation. Signal detection analysis verified the over-all superiority of digital tomography for post extracorporeal shock wave lithotripsy imaging. Calculus detection by conventional and digital tomography is superior to detection by plain abdominal radiography. However, because we did not perform delayed imaging, it is not possible to say what impact digital tomography might have on the management of extracorporeal shock wave lithotripsy patients. PMID- 2231922 TI - Extracorporeal shock wave lithotripsy in patients with bleeding diatheses. AB - Five patients with known bleeding diatheses were treated with extracorporeal shock wave lithotripsy. Specific therapy was administered before extracorporeal shock wave lithotripsy to reverse the bleeding disorder. After treatment each patient was monitored with serial hemoglobin determinations and renal ultrasonography. The course during and after lithotripsy was uneventful in all patients. We conclude that extracorporeal shock wave lithotripsy is a viable option for patients with significant bleeding diatheses provided that specific therapy to reverse the coagulopathic condition is available and used before treatment. PMID- 2231923 TI - Outcome of renal transplantation after urinary diversion and enterocystoplasty: a retrospective, controlled study. AB - A total of 17 patients with intestinal urinary diversion of enterocystoplasty underwent renal transplantation between 1970 and 1988. Patient age ranged from 4 to 35 years (mean age 20 years). The patients were divided into 2 groups. In group 1 (10 patients, 2 of whom required retransplantation) the ureter of the transplanted kidney was implanted into an ileal (7) or colonic (1) conduit or enterocystoplasty (2). In group 2 (7 patients, 1 of whom required a second transplant) the diversion was taken down and the transplanted ureter was implanted into the defunctionalized bladder. There were 14 living related and 6 cadaveric kidneys transplanted. Graft survival rates were 58 and 87% in groups 1 and 2, respectively, with an over-all rate of 70% (14 of 20 kidneys). There was no statistical difference in the graft survival rate between the 2 groups. The complications in group 1 included ureteroileal anastomotic leak (3 patients), ureteroileal stenosis (1), calculus formation (1), urosepsis (1), hyperchloremic metabolic acidosis (1), and wound infection and dehiscence (1). There were no complications in group 2. Renal transplantation into a pre-existing urinary intestinal conduit or augmented bladder does not statistically adversely affect patient or graft survival. However, the complication rate is much higher when the ureter is implanted into an intestinal segment. Therefore, it is preferable whenever possible to implant the ureter into the native bladder. PMID- 2231924 TI - Nephron-sparing surgery for renal cell carcinoma with venous involvement. AB - A nephron-sparing operation recently has been shown to provide extended survival free of disease in selected patients with localized renal cell carcinoma, particularly for tumors of lower stage. To define better the role of conservative surgical treatment in more locally advanced renal cell carcinoma we reviewed 9 patients with venous tumor involvement in solitary functioning kidneys who underwent a nephron-sparing operation. Complete tumor resection with adequate preservation of renal function was accomplished in all cases. Of the 9 patients 5 had no evidence of disease 7 to 93 months (mean 33.2 months) postoperatively. The remaining 4 patients died of metastatic renal cell carcinoma 17 to 47 months (mean 35.5 months) postoperatively, 2 of whom had concomitant local recurrences in the renal remnant. Based on previously reported results of total nephrectomy for renal cell carcinoma with venous involvement and the morbidity associated with renal replacement therapy, we believe that a nephron-sparing operation is a viable option in the management of these patients. PMID- 2231925 TI - Radiation exposure during ureteroscopy. AB - Use of fluoroscopy during ureteroscopy increases the risk of radiation exposure to the urologist and patient. Radiation entrance dosages were measured at skin level in 37 patients, and at the neck, trunk and finger of the urologist, and neck and trunk of the circulating nurse. Radiation exposure time was measured in 79 patients, and was related to the purpose of the procedure and the type of ureteroscope used, whether rigid or flexible. Exposure could be minimized by decreasing the fluoroscopy time. A portable C-arm fluoroscopy unit with electronic imaging and last image hold mode should be used to minimize exposure time. Lead aprons and thyroid shields should be used by the urologist and other personnel in the endoscopy room. PMID- 2231926 TI - The detubularized right colonic segment as urinary reservoir: evolution of technique for continent diversion. AB - Continent diversion of urine via a cecal-right colonic reservoir has been performed at our university hospital since 1977. Several modifications of surgical technique have been devised to prevent problems of urinary leakage and difficulties in catheterization. The current technique, used during the last 3 years on 14 patients, involves use of a detubularized right colonic segment as a reservoir, ileal mesenteric exclusion, fashioning the intussuscepted ileal nipple valve with staples and anchoring of a fascia strip sling around the nipple base to the anterior rectus sheath. Complication from the reservoir outlet occurred in only 1 patient. PMID- 2231927 TI - Adverse impact of fibrin clot inhibitors on intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors. AB - Although intravesical bacillus Calmette-Guerin therapy has proved to be efficacious in the treatment and prophylaxis against tumor recurrence of superficial bladder tumors, its mechanism of action has not been fully elucidated. Previous work has suggested that bacillus Calmette-Guerin organisms attach to the matrix protein, fibronectin, during fibrin clot formation at sites of urothelial disruption and that this attachment was required for the antitumor effect of bacillus Calmette-Guerin to be expressed. Furthermore, drugs inhibiting clot formation were found to abrogate the antitumor effect of intravesical bacillus Calmette-Guerin therapy in a murine bladder tumor model. To examine the effect of inhibitors of fibrin clot formation on the results of intravesical bacillus Calmette-Guerin therapy, a retrospective analysis of 149 evaluable patients receiving intravesical bacillus Calmette-Guerin for superficial bladder tumors was performed. The over-all response rate free of tumor for 29 patients who concomitantly received inhibitors of fibrin clot formation with bacillus Calmette-Guerin therapy was 48%, as compared with 67% for 120 patients who were not receiving these medications (p = 0.0655, chi-square). The most striking difference was noted for patients who failed with recurrent superficial disease. Of the patients who received fibrin clot inhibitors during intravesical bacillus Calmette-Guerin therapy 35% had recurrent superficial tumors compared to only 8% of those who did not receive these drugs during a mean followup of 29.8 plus or minus 11 months (p = 0.005, chi-square). Our study suggests that inhibitors of fibrin clot formation may have an adverse influence on the results of intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors. PMID- 2231928 TI - Outpatient flexible cystoscopy and fulguration of recurrent superficial bladder tumors. AB - Flexible cystoendoscopy and fulguration were used in the outpatient management of 185 patients with superficial bladder tumors followed for 24 months. This method provided optimal surveillance for recurrence and successful tumor control in selected cases. PMID- 2231929 TI - Primary malignant lymphoma of the bladder. AB - We treated 11 patients with primary malignant lymphoma of the bladder. The typical patient is a woman more than 50 years old who presents with urgency and frequency of micturition, and occasionally gross hematuria. Hydronephrosis is present in half of the patients and cystoscopy usually reveals a solid tumor. Partial cystectomy, when feasible, with or without radiotherapy and chemotherapy is the usual treatment modality. When localized to the bladder, malignant lymphoma has an over-all favorable prognosis. PMID- 2231930 TI - Salvage posterior urethroplasty after failed initial repair of pelvic fracture membranous urethral defects. AB - Experience with 20 salvage urethroplasties in patients with pelvic fracture membranous urethral defects who failed previous delayed urethroplasty is presented. A total of 15 patients was successfully managed by 1-stage procedures, 14 by bulboprostatic reanastomosis and 1 by a tubed pedicled island of skin. Substitution urethroplasty with a staged perineoscrotal skin tube inlay was performed in 5 patients in whom an anastomosis could not be achieved either due to an excessively long urethral defect or inelasticity of the anterior urethra precluding its elongation for an anastomosis free of tension. A successful result was achieved in 19 of the 20 patients (95%). The rationale for procedure selection is discussed. PMID- 2231931 TI - Prostacyclin-to-thromboxane A2 ratio in arteriogenic impotence. AB - It has been suggested that penile hypercoagulability predisposes to aging penile vascular changes and impotence, and that elevated thromboxane A2 during erection may contribute to hypercoagulability and atherosclerosis. Since the ratio of the prostacyclin concentration to the thromboxane A2 concentration is constantly maintained in normal hemostatic responses, an imbalance between thromboxane A2 and prostacyclin may be a factor to initiate vascular diseases and decrease blood flow. We assess the usefulness of the prostacyclin-to-thromboxane A2 ratio in penile blood during erection for diagnosis of arteriogenic impotence. The ratio in the arteriogenic impotence group was significantly lower (p less than 0.01) than in the psychogenic and venogenic impotence groups. Therefore, the prostacyclin-to-thromboxane A2 ratio seems to be useful to diagnose arteriogenic impotence. PMID- 2231932 TI - The natural history of Peyronie's disease. AB - The natural history of Peyronie's disease was evaluated in 97 men by means of a questionnaire. Disease duration ranged from 3 months to 8 years. Questions addressed pain, bending, ability for intercourse, over-all effect of the disease, psychological effects, treatments received and degree of disease progression. Approximately 40% of the patients found pain, bending, ability for intercourse and over-all effects to be unchanged during the course of the disease. Bending and ability for relations worsened in 40% of the patients during the same interval, while only 6% had worsening of pain. Of the patients 77% reported psychological effects due to Peyronie's disease, which improved in 28%, did not change in 36% and worsened in 36%. Over-all, 13% of the patients believed the disease to be one of gradual resolution, 47% believed there had been little or no change and 40% believed that the disease pattern was one of gradual progression. We found no statistically significant association between disease duration and spontaneous improvement in penile bending. A similar lack of statistical significance was found when improvement in a variety of categories was compared in patients who received no therapy versus those who received a variety of conventional medical therapies. PMID- 2231933 TI - Ultrasonographic characteristics of the seminal vesicles after ejaculation. AB - A total of 12 men from a sperm donor bank underwent transrectal ultrasonography before and after ejaculation to investigate possible changes that could influence interpretation of seminal vesicle ultrasonography. The mean length of the seminal vesicles was 2.98 cm. before and 2.95 cm. after ejaculation. The anteroposterior diameter decreased only from 0.59 to 0.52 cm. Minimal differences were noted between the right and left seminal vesicles, and the greatest variation in size in an individual was only 3 mm. These results indicate that interpretation of seminal vesicle anatomy as seen by ultrasonography does not depend upon the temporal relationship to ejaculation. PMID- 2231934 TI - Clinical and pathological findings in prostates following intravesical bacillus Calmette-Guerin instillations. AB - The prostates of 36 patients who were treated with intravesical bacillus Calmette Guerin were evaluated by digital rectal examination and transrectal ultrasonography. When abnormal palpatory and/or ultrasonographic findings were detected, core needle biopsies from the suspicious areas were performed. Of the 36 patients 20 underwent biopsies of the prostate. Pathological findings revealed typical granulomas in 8 patients (3 caseating and 5 noncaseating multifocal granulomas). Nonspecific chronic prostatitis was noted in 4 patients and benign prostatic hyperplasia was noted in 8. The number of bacillus Calmette-Guerin instillations ranged from 6 to 19. The interval from initiation of therapy to biopsy ranged from 1.5 to 14.5 months. Caseating granulomas were found during the early course of bacillus Calmette-Guerin instillations (1.5 to 3.0 months), whereas noncaseating granulomas were detected at later stages (4 to 14.5 months). These findings present a high incidence of granuloma formation in patients treated with intravesical bacillus Calmette-Guerin. The duration of therapy is a determinant factor in the induction of granuloma type. PMID- 2231935 TI - The prognostic value of modal deoxyribonucleic acid in low grade, low stage untreated prostate cancer. AB - We selected for a prospective surveillance study 167 patients with untreated grades 1 and 2 prostate cancer. The tumors were classified regarding modal deoxyribonucleic acid value (ploidy) by flow cytometry, cytological grade by transrectal fine needle aspiration biopsy and local tumor stage. Of the patients 146 could be evaluated. Mean followup was 50 months. The initial ploidy was statistically correlated to cytological grade but not to initial local tumor stage, prostatic acid phosphatase activity or patient age. Initial ploidy and cytological grade had a prognostic value regarding local tumor progression when considered as single predictors and in combination. Two patients with diploid and 8 with nondiploid tumors initially had metastases during the surveillance. Five patients (1 with diploid and 4 with nondiploid disease) died of prostatic cancer. Modal deoxyribonucleic acid value and cytological grade were of prognostic value in untreated prostate cancer. PMID- 2231936 TI - Evaluation of tumor progression by repeated fine needle biopsies in prostate adenocarcinoma: modal deoxyribonucleic acid value and cytological differentiation. AB - Repeated fine needle aspiration biopsies of the prostate were taken during a period of 24 months or more from 84 patients with untreated prostate cancer. Serial followup regarding modal deoxyribonucleic acid values and cytological differentiation of the tumor cells was possible in 72 and 78 patients, respectively. During followup the modal deoxyribonucleic acid values in the tumor cells changed towards an increased aneuploidy in 17 patients and the cytological differentiation decreased in 18. These findings of a change in modal deoxyribonucleic acid values and cytological differentiation of prostate cancer cells during the course of untreated patients support the concept of a gradual dedifferentiation of prostate cancer. PMID- 2231937 TI - Total pelvic exenteration with simultaneous bowel and urinary reconstruction. AB - The technique of total pelvic exenteration with simultaneous bowel and urinary reconstruction is described as a surgical option for the management of pelvic sarcoma in adults and for highly selected patients with other types of advanced pelvic malignancy. The surgical technique is presented in detail as performed in a 43-year-old man who presented with extensive primitive pelvic sarcoma. We believe that this approach may provide the benefits of an exenterative operation without the undesirable psychosocial sequelae of a permanent colostomy and external urinary diversion. PMID- 2231938 TI - The value of leak pressure and bladder compliance in the urodynamic evaluation of meningomyelocele patients. AB - A total of 61 patients with myelodysplasia underwent water cystometry and electromyography of the external sphincter. Of these patients 27 underwent video fluorourodynamics as a part of preoperative evaluation or instead of a voiding cystometrogram. Renal quantitative scintillation camera studies detected 7 patients with mild upper tract deterioration, even when other tests failed to do so. A total of 31 patients had upper tract deterioration as detected by excretory urography, ultrasound and/or renal scan studies, and were designated as group 1, while 30 had normal upper tracts and were designated as group 2. Bladder compliance in group 1 was significantly lower than that in group 2 (4.5 versus 11.3 ml./cm. water, p = 0.001). Leak pressure in group 1 was significantly higher than in group 2 (42.3 versus 26.1 cm. water, p = 0.019). In summary, patients with evidence of upper tract deterioration had lower bladder compliance and higher leak pressure than patients with normal kidneys. PMID- 2231939 TI - Renal autotransplantation in children: a successful treatment for renovascular hypertension. AB - Renovascular hypertension in children is not a common disease. With improved surgical technique the incidence of nephrectomy has decreased and renovascular reconstruction is currently the preferred method to manage this entity. Between 1977 and 1988, 21 patients with renovascular hypertension were treated at our hospital: 7 patients 6 to 16 years old underwent renal autotransplantation. Of the children 4 had unilateral and 3 had bilateral disease requiring bilateral autotransplantation. Autotransplantation was performed by anastomosis of each renal artery end-to-side to the common iliac artery. The renal veins were anastomosed end-to-side to the common iliac veins. The ureters were left intact in all but 1 patient who required a bench operation. Of the 4 patients who had a unilateral procedure 3 are cured and 1 is improved with a normal blood pressure on a small dose of antihypertensive medication. The 3 patients with bilateral autotransplants are cured. These results, with normalization of the blood pressure in 86% of the patients and improvement in blood pressure in 14% with a patency rate of 87%, are similar to other reported reconstructive modalities in children. PMID- 2231940 TI - Management of children with myelodysplasia: urological alternatives. AB - Recent reports have suggested that the prophylactic use of clean intermittent catheterization in selected infants with myelodysplasia and with normal upper tracts may prevent their deterioration. The selection of these patients at risk depends on urodynamic criteria. We reviewed our experience with clean intermittent catheterization instituted when upper tract deterioration was found. Of 130 patients with myelodysplasia followed at our clinic 25 (19%) had or presented with radiological upper urinary tract deterioration. A total of 21 patients had vesicoureteral reflux and 4 had hydronephrosis without reflux. Treatment consisted of clean intermittent catheterization alone in 5 patients and combined with anticholinergic medication in 16. Four patients with no post-void residual urine were carefully observed without intervention. Urodynamic evaluation was performed selectively in 11 of these 25 patients for persistence of upper urinary tract deterioration or urinary incontinence after institution of treatment. Of the 21 children with reflux 19 (90%) had resolution or improvement for an average followup of 47 months. Hydronephrosis completely resolved in the 4 patients without reflux. Thus, the over-all resolution or improvement rate was 92% for an average of 41 months. Although these excellent results may not be superior to the prophylactic use of clean intermittent catheterization, they validate the assumption that upper tract deterioration can be reversed. The application of current urodynamic selection criteria may result in overtreating a significant number of infants who otherwise may not have upper tract deterioration. Further refinements in these criteria may be necessary to select better not only patients at risk but also to determine the frequency of imaging necessary in this urologically heterogeneous population. In addition, careful consideration should be given to urethral dilation as a third and equally viable alternative to prevent upper tract deterioration. PMID- 2231941 TI - Isolated primary aldosteronism in a patient with adrenal carcinoma and XY/XXY mosaic Klinefelter's syndrome. AB - Although breast cancer, germ cell tumors and other neoplasms are known to occur in patients with Klinefelter's syndrome, adrenal carcinoma has not yet been reported in such patients. We describe a rare case of severe primary aldosteronism as the unique manifestation of a large adrenocortical carcinoma in a patient with Klinefelter's syndrome. Complete biological and hormonal evaluation was performed. Surgical treatment was successful and the patient remained asymptomatic with normal biological and hormonal values after 1 year of followup. PMID- 2231942 TI - Renal scintigraphy in the diagnosis and surgical management of a patient with caliceal colic: a case report. AB - A patient with persistent renal colic and a caliceal stone is presented. Furosemide renography, commonly used to differentiate functional stasis from mechanical obstruction of an entire kidney or duplicated collecting system, can make this determination at the caliceal level. As in this case such determination can affect clinical management of the patient. PMID- 2231943 TI - A giant renal artery aneurysm diagnosed post partum. AB - We report a case of a 5.8 cm. right renal artery aneurysm diagnosed intact 8 weeks post partum. Rupture of a renal arterial aneurysm during pregnancy is a rare but well described catastrophic event. There are no previous reports of an intact renal artery aneurysm diagnosed either ante partum or post partum. To our knowledge, this also represents the largest reported renal artery aneurysm. The aneurysm was repaired successfully with kidney salvage and closure of the fistulous connection to the renal vein. PMID- 2231944 TI - Recurrent vesicogluteal fistula due to sequestrum. PMID- 2231945 TI - Nonsteroidal anti-inflammatory drugs in the treatment of eosinophilic cystitis. AB - A 30-year-old white woman with urinary frequency, left costovertebral angle pain and hematuria had left hydronephrosis, a marked decrease in bladder capacity and severe eosinophilic cystitis on biopsy. She was treated with a nonsteroidal anti inflammatory drug and an antihistamine, with a dramatic, complete and rapid recovery. The nonsteroidal anti-inflammatory drug was believed to have been responsible for the favorable outcome, since antihistamines have not produced reliable benefits in this disease. Nonsteroidal anti-inflammatory drugs are recommended in cases of eosinophilic cystitis. PMID- 2231946 TI - Reverse coitus: mechanism of urethral injury in male partner. AB - Reverse coitus, a rarely used sexual position, makes the male urethra more vulnerable to injury from the pubic arch and symphysis pubis of the female partner. Severe pain, bleeding and immediate detumescence were observed in 3 patients. The lesion usually occurred at the fossa navicularis, responded well to conservative management and did not hinder micturition. Potency has been well preserved in all 3 patients. PMID- 2231947 TI - Transrectal ultrasonography in the evaluation of the infertile man: a report of 3 cases. AB - The traditional evaluation of the infertile man with azoospermia or low ejaculate volume includes determination of serum testosterone and follicle-stimulating hormone levels, a seminal fructose test, post-ejaculate urinalysis and, sometimes, vasography. Transrectal ultrasonography, a technique currently familiar to most urologists, recently has been added to our diagnostic armamentarium. This office-based imaging procedure provides an accurate assessment of the prostate, ejaculatory ducts and seminal vesicles, which can be helpful in the evaluation of certain infertile patients. We describe 3 patients who presented with either azoospermia or decreased ejaculate volume in whom transrectal ultrasonography had a critical role in the fertility evaluation. The clinical indications for and interpretation of transrectal ultrasonography in the infertile population are described. Transrectal ultrasonography currently is the most accurate, inexpensive and readily available noninvasive imaging technique used to diagnose obstruction of the ejaculatory ducts in the infertile patient with either azoospermia or low ejaculate volume. PMID- 2231948 TI - Gonadoblastoma in an anatomically normal man: a case report and literature review. AB - Gonadoblastoma, a rare gonadal neoplasm, presents most frequently in phenotypic female or phenotypically male patients with dysgenetic gonads or undescended testes. To date, only 2 cases of gonadoblastoma have been reported in anatomically normal male patients with scrotal testes. Both of these patients presented with testicular masses and germ cell tumors. We report a case of a genotypically and phenotypically normal, fertile man with descended testes who on evaluation for chronic orchialgia had a gonadoblastoma unaccompanied by a germ cell neoplasm. The tumor was nonpalpable and was initially discovered on scrotal ultrasound. PMID- 2231949 TI - Re: Radiographic assessment of renal trauma: a 10-year prospective study of patient selection. PMID- 2231950 TI - Ureteral stenosis in renal transplantation. PMID- 2231951 TI - Re: Review of an 8-year experience with modifications of endoscopic suspension of the bladder neck for female stress urinary incontinence. PMID- 2231952 TI - Size considerations for custom penile prostheses. PMID- 2231953 TI - Re: Carcinoma in situ of the testis. PMID- 2231954 TI - The kinetics of cellular proliferation in rat urinary bladder treated with N butyl-N-(4-hydroxybutyl)nitrosamine. AB - The cellular proliferation of the bladder epithelium was determined sequentially in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The incorporation of bromodeoxyuridine (BrdUrd) into the DNA synthesis phase was determined by an in vitro labeling technique. The percentage of labeled cells was expressed as the labeling index (LI). The average LI values in normal subjects and cancer-bearing subjects were 5.1(%) and 24.2(%) respectively. With the transition of the bladder epithelium from simple hyperplasia to cancer, the LI values of the bladder epithelium were increased. Cases of papillary or nodular (PN) hyperplasia were divided into two types according to the localization of the BrdUrd-labeled cells. The LI in PN hyperplasia was 12.4(%); the difference from cancer was significant. In another experiment, the effect of partial cystectomy on bladder tumors was examined. The group with partial cystectomy showed increases in grade and stage of cancer, and the LI of cancer was more than that in the group without partial cystectomy. The results indicate that partial cystectomy may play a role as promotor for bladder tumors. The current study may be of more practical value than is the conventional one for investigating the histogenesis and progression of human bladder cancer. PMID- 2231955 TI - Relaxation mechanisms of antispasmodics papaverine and thiphenamil on the human corpus cavernosum. AB - The relaxation mechanism of the antispasmodics, papaverine and thiphenamil on isolated human corpus cavernosum (CC) was investigated. CC tissues were obtained from 12 impotent men undergoing surgery for insertion of penile prostheses. CC preparations were mounted in a tissue bath and the isometric tension was recorded. Papaverine and thiphenamil consistently inhibited high-potassium ([K]) induced contractions in a dose-dependent manner. Noradrenaline (NA)-induced contractions were inhibited by both agents in a non-competitive manner. The pD'2 values were 4.77 +/- 0.20 for papaverine and 4.58 +/- 0.13 for thiphenamil. Papaverine at 10(-4) M, the concentration at which high-[K]-induced contraction was abolished, suppressed NA-induced contraction by approximately 85%. In the Ca2(+)-free solution containing two mM EGTA, NA-induced contraction was suppressed by approximately 90%. This contraction was inhibited by papaverine or thiphenamil in a dose-dependent manner and was abolished by papaverine at 10(-4). These results suggest that papaverine and thiphenamil relax CC tissue by the inhibition of extracellular Ca2+ influx (mainly voltage-dependent Ca2+ influx) and by the inhibition of release and/or storage of intracellular stored Ca2+. PMID- 2231956 TI - The use of prostaglandin F2 alpha for the prophylaxis of cyclophosphamide induced cystitis in rats. AB - It is well-established that cystitis is a significant cause of morbidity after cyclophosphamide administration in clinical populations. We induced hemorrhagic cystitis in rats using cyclophosphamide and compared controls to those pretreated with prostaglandin F2 alpha. Rats were then evaluated for differences in bladder weights, gross edema, gross bleeding, and histologic changes. The weights of the bladders which had been treated with cyclophosphamide were 94% greater than the controls. The weights of the bladders which were pretreated with prostaglandin F2 alpha before cyclophosphamide were only 19% greater than controls. Significant differences were found between cyclophosphamide controls and prostaglandin F2 alpha pretreated groups for gross weight (p less than .0005), gross edema (p less than .0005), and histology (.0005 less than p less than .005). We conclude that prostaglandin F2 alpha may be helpful in preventing cyclophosphamide induced cystitis. PMID- 2231957 TI - Pressure threshold for shock wave induced renal hemorrhage. AB - Studies were performed with an interest in determining a pressure threshold for extracorporeal shock wave induced renal damage. Histological evidence of intraparenchymal hemorrhage was used as an indicator of tissue trauma. Depilated C3H mice were anesthetized and placed on a special frame to enhance visualization and treatment of the kidneys in situ. A Wolf electrohydraulic generator and 9 French probe designed for endoscopic use were utilized to expose the kidneys to 10 double spherically divergent shock waves. Measurements of the shock waves revealed two positive pressure peaks of similar magnitude for each spark discharge. The kidneys were exposed to different peak pressures by choice of distance from the spark source and were removed immediately after treatment for histologic processing. A dose response was noted with severe corticomedullary damage apparent following 15 to 20 MPa shocks. Hemorrhage was more apparent in the medulla where evidence of damage could be seen following pressures as low as three to five MPa. When a latex membrane was interposed to prevent possible collapse of the initial bubble from the spark source against the skin surface, histological evaluation revealed substantial reduction of severe tissue damage associated with the highest pressures tested, 20 MPa. However, the threshold level for evidence of hemorrhage remained about three to five MPa. Hydrophonic measurements indicated that the membrane allowed transmission of the acoustic shock waves and suggested that collapse of the bubble generated by electrohydraulic probes may have local effects due to a cavitation-like mechanism. PMID- 2231958 TI - Physiologic and pathologic alterations associated with ultrasonically generated shock waves. AB - Kidneys of 25 dogs were treated with ultrasonic shock waves and examined for both physiologic and pathologic changes. The number of pulses ranged from 2,000 to 8,000. The rate of the shock waves varied from one to 20 pulses per second. The difference in pulse rate did not affect the changes seen either acutely or in the delayed examination of the kidneys during the repair process. The physiologic and pathologic changes which occurred involved the renal tubule to a greater degree than the glomerulus. These alterations were resolving by one week following exposure to the shock waves. PMID- 2231959 TI - Cell injury associated calcium oxalate crystalluria. AB - Renal tubular cell damage, resulting in membranuria, was induced by the administration of subcutaneous gentamicin to male Sprague-Dawley rats. One group of rats received gentamicin only, while a second group was given gentamicin plus ethylene glycol in drinking water at a concentration which increased urine oxalate but alone did not cause calcium oxalate crystalluria. Crystalluria occurred early in the combined treatment groups and persisted for the duration of the experiment. Crystalluria was not present in animals receiving gentamicin or ethylene glycol only. These results suggest that cellular fragments can serve as heterogeneous foci for the nucleation of calcium oxalate crystals. PMID- 2231960 TI - Effect of thiorphan on the response of guinea-pig isolated urinary bladder to exogenous and endogenous tachykinins. AB - Thiorphan, a well known inhibitor of 'enkephalinase' (endopeptidase 24.11) potentiated and prolonged the contractile response to substance P (SP) and neurokinin A (NKA) on strips of the guinea-pig isolated urinary bladder and this effect was evident both in presence and absence of the mucosal layer. Thiorphan also enhanced and prolonged the capsaicin-induced contraction in strips from the bladder dome which is thought to be mediated by release of endogenous tachykinins. Exposure to capsaicin produced simultaneous release of SP- and tachykinin-like immunoreactivity both in presence and absence of mucosa. This effect of capsaicin was potentiated by thiorphan. Endopeptidase 24.11 activity was detected in the guinea-pig urinary bladder, being more concentrated in the mucosal than the muscular layer. These findings indicate that endopeptidase 24.11 terminates the activity of tachykinins in the guinea-pig urinary bladder and modulates the intensity of the biological response produced after their release from peripheral endings of sensory nerves. PMID- 2231961 TI - Doppler color-flow images from a stenosed arterial model: interpretation of flow patterns. AB - The capability of the recently introduced Doppler color-flow mapping devices to accurately detect flow patterns in the region of an arterial stenosis was evaluated by use of an in vitro flow model. Pulsatile flow simulating that in a low-resistance vessel was induced through a straight acrylic tube, which alternatively contained axisymmetric stenoses of 0%, 20%, 40%, 60%, and 80% diameter reduction. Doppler color-flow mapper images were taken in realtime along the tube midplane from 0 to 8 diameters downstream of each stenosis. Comparison of the Doppler color-flow mapping results with similarly recorded flow visualization (hydrogen bubble) images showed a close correspondence of key features of the flow, including detection of a high-velocity, centerline jet and near-wall separated flow zones. Distinctive flow patterns exist with each stenotic case, and these should be of considerable value in diagnosing clinical disease conditions. PMID- 2231962 TI - Everted cervical vein for carotid patch angioplasty. AB - Because of the theoretic benefits of autologous vein we undertook an investigation to evaluate cervical veins (facial, external jugular) as patch material after carotid endarterectomy. A device that stimulated both circumferential fixation by sutures and radial tension exerted on in vivo patches was constructed to measure burst strength of tissue. Mean bursting pressure for groin saphenous vein (n = 10) was 94.5 +/- 15.1 pounds per square inch (psi), 75.5 +/- 8.9 psi for ankle saphenous vein (n = 10), 83.3 +/- 14.5 psi for everted (double layer) cervical vein (n = 5) and 10 +/- 3.3 psi for single layer cervical vein (n = 5). No significant differences between saphenous vein at any level and everted (double layer) cervical vein, but all were significantly different from single layer cervical vein (p less than 0.05). From June 1987 through November 1989, 19 patients underwent 21 carotid endarterectomies complemented with adjunctive everted cervical vein patch angioplasty. Indications for surgery were asymptomatic stenosis (53%), transient ischemic attack (29%), and cerebrovascular accident with recovery (18%). All patients were studied after surgery with duplex scanning. Asymptomatic recurrent stenosis was observed in one patient. Transient hypoglossal nerve dysfunction occurred in one other patient. One postoperative death occurred as a result of massive aspiration. These results indicate that everted cervical vein is comparable to the saphenous vein in resistance to bursting and can yield similar results as patch material after carotid endarterectomy. Accordingly, saphenous vein can be spared and lower extremity incisions avoided.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2231963 TI - Inflammatory abdominal aortic aneurysm masquerading as occlusion of the inferior vena cava. AB - Inflammatory aneurysms are an uncommon disorder that represent between 5% and 10% of abdominal aortic aneurysms. Their presentation is often variable and may include pain and obstruction of adjacent anatomic structures. This report describes a 68-year-old man who sought treatment after insidious onset of progressive bilateral lower extremity edema over a 6-month period. Noninvasive studies were suggestive of bilateral iliac vein occlusion, and a venogram showed a nearly obstructed vena cava from external compression. A CT scan showed a thick walled infrarenal abdominal aneurysm. At exploration an inflammatory abdominal aortic aneurysm was found. Because of the presence of dense inflammatory changes surrounding the aneurysm and extending into the pelvis, the surgical procedure of choice was an aortobifemoral bypass graft done with Dacron. The aneurysmal wall was debrided from the vena cava. His postoperative course was uneventful, his edema resolved, and follow-up noninvasive studies were normal. Postoperative venography showed resolution of the extrinsic compression of the vena cava. PMID- 2231964 TI - Material and structural characterization of human saphenous vein. AB - Saphenous vein patch rupture after carotid endarterectomy is an infrequent but devastating complication. This study was undertaken to evaluate the material and structural properties of fresh human saphenous veins to understand the causes of this complication. Segments of saphenous veins were obtained from 22 patients from vein harvested during coronary artery bypass surgery. Ninety-three specimens, oriented in both circumferential (n = 45) and longitudinal (n = 48) directions, were prepared from the available vein segments for testing. Specimens were mounted on specially designed grips and then subjected to uniaxial tension testing. For each specimen the following material and structural parameters were determined: vessel diameter, tensile stiffness, failure and ultimate forces, and tensile modulus, failure stress, and strain. The physical properties of specimens evaluated in longitudinal orientations and thus limit the inherent strength of the vein. The physical properties of circumferentially tested vein specimens were negatively correlated to age, female gender, diabetes, and hypertension. The data obtained in this investigation suggest that age, hypertension, as well as diabetes and gender may adversely influence the circumferential tensile strength of human saphenous veins used as patch grafts. PMID- 2231965 TI - An animal model for instructing and the study of in situ arterial bypass. AB - A canine model that used the cephalic vein to bypass from the brachial to the ulnar artery was designed for use in instructing and evaluating surgical technique needed for constructing an in situ arterial bypass. This model was used for instructing vascular residents in the in situ vein bypass technique. The use of this model enabled the resident to become more adept with the instruments for valve incision and construction of small vessel anastomosis. The improvement in the resident's operative technique was reflected by a decrease in the number of technical complications (missed valves, missed arteriovenous fistulas, poorly constructed anastomoses) and improved patency rate. PMID- 2231966 TI - Indications for distal arterial reconstruction in the presence of palpable pedal pulses. AB - Eight patients with severe pedal ischemia in the presence of palpable foot pulses are described. All had atherosclerosis, and seven patients also had diabetes. There were two anatomic patterns of disease, including supramalleolar obstruction with reconstitution of pulsatile flow in three patients and segmental occlusion of the pedal vessels in five. All patients underwent arterial reconstructive surgery. Patency was sustained in six patients, with limb salvage in five and below-knee amputation in one patient for persistent necrosis and infection of an open amputation. Of the two eventual bypass failures, a transmetatarsal amputation continued to heal in one patient, and the other required amputation below the knee. Palpable pedal pulses and satisfactory ankle/brachial indexes did not rule out the presence of surgically correctable distal arterial occlusive disease. Therefore arteriography is indicated in any patient with persistent forefoot ischemia that fails to respond to conservative measures. The safety and patency of the distal reconstructive procedures performed in this series suggest that salvage of weight-bearing tissue and rapid healing, as well as limb salvage, are legitimate indications for revascularization. PMID- 2231967 TI - Femur fracture with limb shortening causing occlusion of a polytetrafluoroethylene femoral popliteal graft. AB - Traumatic occlusion of lower extremity polytetrafluoroethylene arterial grafts is exceedingly rare. We report a patient who suffered a supracondylar femur fracture resulting in shortening of her right lower extremity with kinking and thrombosis of her above-knee polytetrafluoroethylene arterial graft. This is the first report in the English language of prosthetic graft occlusion as a result of traumatic limb shortening. The graft thrombus was successfully lysed by use of intraarterial urokinase, and the kink was repaired by graft resection and reanastomosis. The mechanism of injury and treatment are discussed. PMID- 2231968 TI - Intraabdominal hemorrhage as a result of segmental mediolytic arteritis of an omental artery: case report. AB - This article describes the fifth reported case of segmental mediolytic arteritis and the second in a survivor. The patient had intraabdominal bleeding as a result of a ruptured omental artery. The pathologic and arteriographic findings are described. The pathology is characterized by segmental disruption of the medial smooth muscle cells and the initiation of mediolysis. Mediolysis is associated with marked segmental thinning of the vessel wall, often with only the adventitia intact. Fibrin is deposited at the adventitial and medial surfaces, and hemorrhage into the media may occur. As in this reported case, lysis of the adventitia leads to sudden, often catastrophic intraabdominal hemorrhage. Little associated adventitial inflammation occurred. Segmental mediolytic arteritis seems to involve the intra-abdominal muscular arteries in elderly patients with nonspecific abdominal symptoms. An angiogram showed patchy areas of narrowing involving ileal, gastroduodenal, and renal arteries that correlated with the pathologic findings observed in the excised omental arteries. PMID- 2231969 TI - Popliteal artery agenesis: a new anatomic variant. AB - Agenesis of the popliteal artery has not been described as a vascular anomaly in the lower extremity. This case report describes congenital absence of the popliteal artery discovered during operative exploration after a traumatic injury to the lower extremity. The preoperative arteriogram suggested acute occlusion of the popliteal artery. Intraoperative exploration and arteriography were consistent with agenesis of the popliteal arterial segment, and postmortem examination confirmed these arteriographic and intraoperative observations. Embryologically, failure of the middle portion of the sciatic artery to persist would account for this anomaly. A review of series reporting congenital anomalies of the lower extremity vasculature failed to discover previous mention of this particular abnormality. Agenesis of the popliteal artery should be included among those vascular anomalies that may affect management of lower extremity vascular disease. PMID- 2231970 TI - Disseminated histoplasmosis with embolic endovascular complications: a case report. AB - A 57-year-old man had subacute embolic ischemia of his right foot and subsequent acute embolic ischemia of his left foot after angiography. Thrombus removed at the time of the left femoral thromboembolectomy grew Histoplasma capsulatum confirming the diagnosis of disseminated histoplasmosis. Surgical revascularization of the right leg and parenteral amphotericin B was followed by chronic ketoconazole therapy for 16 months. The patient has remained asymptomatic at 30 months after operation. Effective treatment of endovascular infection with ischemic complications of Histoplasmosis requires surgical revascularization and intensive chemotherapeutic intervention. Histoplasmosis is a ubiquitous infection in endemic areas that often has an asymptomatic subclinical course. Involvement of the cardiovascular system is rarely reported. Previous case reports have described infected cardiac valves and aortic aneurysms. This report describes the uncommon presentation of disseminated Histoplasma capsulatum infection as a peripheral embolic event and the successful management with revascularization combined with systemic amphotericin B followed by ketoconazole therapy. PMID- 2231971 TI - Indirect revascularization of the lower extremity by means of microvascular free muscle flap--a preliminary report. AB - We describe the treatment of a patient with end-stage peripheral vascular disease and ischemic ulceration of the lower extremity in whom an obliteration of the distal arterial bed precluded conventional arterial reconstruction. A nonhealing dorsal foot ulcer was debrided, and soft tissue reconstruction was accomplished by the free microsurgical transfer of a muscle flap to the distal lower extremity. Arterial inflow to this free flap was provided by a contralateral reversed saphenous vein graft from the proximal arterial tree of the leg. This procedure resulted in a healed wound, stable coverage, and limb salvage. The patient also noted complete relief of rest pain and improvement in his claudication symptoms. A follow-up arteriogram was done 2 months after surgery. Contrast injection directly into the artery of this flap showed new blood vessel growth from the muscle flap into the foot with anastomoses of these "new vessels" to the patient's native circulation. This experience suggests that limb salvage may be possible by the free microvascular transplantation of a muscle flap onto the limb in selected patients whose limbs are deemed "nonreconstructible." PMID- 2231972 TI - Unusual aspects of aortovenous fistulas associated with ruptured abdominal aortic aneurysms. AB - Three unusual cases of an abdominal aortic aneurysm spontaneously rupturing into the retroperitoneum and an adherent posterior vein are reported. No patient demonstrated signs or symptoms of an aortovenous fistula before surgery. Emergent surgery prevented extensive preoperative diagnostic testing. The three abdominal aortic aneurysms were very large and averaged 13 cm in diameter. One fistula involved an inflammatory aneurysm, which is the fifth such case reported. The aortic fistulas were to the inferior vena cava (158 other cases reported in the English-language literature), a left renal vein (16 other cases reported), and an iliac vein (7 other cases reported). Routine use of the cell-saver, oversewing of the fistula from within the aneurysm, and a heightened awareness that this unusual complication is more common in the presence of a very large, ruptured abdominal aortic aneurysm should improve survival. PMID- 2231973 TI - Popliteal artery occlusion caused by cystic adventitial disease: successful treatment by urokinase followed by nonresectional cystotomy. AB - Preoperative diagnosis of an occluded popliteal artery caused by cystic adventitial disease allowed use of urokinase to successfully dissolve secondary thrombosis. Subsequent non-resectional adventitial cystotomy and evacuation of cyst contents allowed lasting restoration of a patent arterial lumen and return of normal distal pulses. This nongrafting technique may serve as a model for future patients with occluded arteries caused by this condition. PMID- 2231974 TI - Deep vein obstruction and leg swelling caused by femoral ganglion. AB - We present a case of a rare ganglion cyst originating from the hip joint and compressing the common femoral vein producing signs and symptoms that mimicked a deep vein thrombosis. Excision of the mass promptly restored normal venous return. This condition has not been previously reported in the English-language medical literature. PMID- 2231975 TI - Hemodynamic characteristics of failing infrainguinal in situ vein bypass. AB - The successful follow-up of distal arterial reconstructions for the identification of the failing bypass in the postoperative period hinges on a knowledge of the natural history of flow characteristics in these reconstructions. Over a 4-year period resting and hyperemic bypass flow, fistula flow, conduit diameter, and distal peak systolic velocity of 350 in situ bypasses were measured serially. B-mode ultrasound imaging of the entire bypass was performed to identify specific stenoses. Measurements were performed 5 to 9 days after operation, every 2 months for the first year, and every 6 months thereafter. Distal bypass flow less than 25 ml/min, a ratio of hyperemic/resting distal bypass flow less than 2.5, and vein size less than or equal to 3.0 mm inner diameter all correlated with bypass stenosis (greater than 50%) or occlusion (p less than 0.01). Contrary to previous studies, a distal peak systolic velocity of less than 45 cm/sec did not correlate with bypass stenosis or occlusion. A low distal peak systolic velocity did correlate with bypass stenosis or occlusion in bypasses larger than or equal to 3.5 mm inner diameter (p less than 0.03). However, no combination of these factors was able to accurately predict preocclusive stenosis or occlusion. Distal bypass flow was highest initially but reached a plateau 6 to 12 months after operation. Fistula flow, although very high initially, showed marked decrement with time. PMID- 2231976 TI - Angioscopy guided semiclosed technique for in situ bypass. PMID- 2231977 TI - Should vascular surgery become an independent specialty? PMID- 2231978 TI - Perspectives from the Residency Review Committee. PMID- 2231979 TI - Vascular surgery--a specialty of surgery. PMID- 2231980 TI - Should vascular surgery become an independent specialty? Perspective of a program chairman and Residency Review Committee member. PMID- 2231981 TI - Should vascular surgery become an independent specialty? Implications of data about operative experience. PMID- 2231982 TI - Accreditation of vascular laboratories. PMID- 2231983 TI - Extended vein graft donation from a single lower extremity. PMID- 2231984 TI - Physicians hear about incontinence. PMID- 2231985 TI - Decade may be more than half over before acellular pertussis vaccines arrive on scene. PMID- 2231986 TI - Pertussis toxins, other antigens become likely targets for genetic engineering. PMID- 2231987 TI - British firm halts vaccine manufacture, research. PMID- 2231988 TI - From the Food and Drug Administration. PMID- 2231989 TI - From the Centers for Disease Control. Vaccine-preventable diseases among adults: standards for adult immunization practice. PMID- 2231990 TI - Frozen pre-embryos. PMID- 2231991 TI - Pertussis vaccine encephalopathy. PMID- 2231992 TI - Dobutamine overdose. PMID- 2231993 TI - The pituitary incidentaloma beyond the first year of follow-up. PMID- 2231994 TI - Admission source to the medical intensive care unit predicts hospital death independent of APACHE II score. AB - This study was conducted to determine if the source of admission to the medical intensive care unit (MICU) is associated with hospital death independent of the Acute Physiology and Chronic Health Evaluation (APACHE) II score. We calculated APACHE II scores and predicted risks of hospital death for 235 patients who were admitted to the MICU. The predicted death rate was the same as the actual rate for patients who were admitted directly from the emergency department (25% vs 22%), but was less than the actual rate for patients who were transferred from hospital floors (38% vs 55%), the medical intermediate care unit (32% vs 59%), and other hospitals (21% vs 36%). Logistic regression analysis confirmed an independent association between the MICU admission source and risk of death. Our findings suggest that APACHE II does not measure illness severity accurately in all patients who are admitted to intensive care units. If our results are generalizable, using APACHE II to compare intensive care outcomes among hospitals could lead to wrong conclusions about quality of care. Improving predictions of hospital death rates among patients who are in MICUs may require the inclusion of new types of information in the classification system. PMID- 2231995 TI - Head injury--associated deaths from motorcycle crashes. Relationship to helmet use laws. AB - A review of US mortality data from 1979 to 1986 identified 15,194 deaths and nearly 600,000 years of potential life lost before age 65 years that were associated with head injuries from motorcycle crashes. White males from 15 to 34 years of age accounted for 69% of the deaths. The rate of motorcycle-related deaths associated with head injury declined modestly between 1979 and 1986 (19% using rates based on resident population and 8% based on motorcycle registrations). Population-based rates adjusted for age, sex, and race in states with partial or no motorcycle helmet-use laws were almost twice those in states with comprehensive helmet-use laws. Two states that weakened their helmet-use laws from comprehensive to partial during the study period had increases in motorcycle-related head injury death rates (184% and 73%), and one state that strengthened its law from partial to comprehensive had a decline in its death rate (44%). Head injury death rates based on motorcycle registrations were also lowest in states with comprehensive helmet-use laws. Since helmets reduce the severity of nonfatal head injuries in addition to lowering the rate of fatal injuries, we urge the adoption and enforcement of comprehensive motorcycle helmet use legislation. PMID- 2231996 TI - Visual impairment in a rural Appalachian community. Prevalence and causes. AB - A population-based survey of 1136 subjects aged 40 years and older was conducted in a rural valley of Kentucky to determine the nature and extent of visual disability in an underserved area of rural America. Data on corrected visual acuity and ocular history, along with demographic, socioeconomic, and health care utilization parameters, were gathered. Those subjects with an acuity below 20/60 in either eye underwent a comprehensive ophthalmologic examination. The prevalence of binocular blindness (acuity worse than 20/400 in the better eye) was 0.44% and of monocular blindness (acuity worse than 20/400 in one eye) was 3.3%, approximately twice the national rates. The chief cause of bilateral visual impairment was macular degeneration among men and cataract among women. Cataract, trauma, and amblyopia were the major causes of monocular visual impairment in both sexes. Risk factor analysis revealed younger age, higher education, active employment, access to a health care facility, and comprehensive health insurance coverage to be inversely associated with visual impairment. PMID- 2231997 TI - Aspirin increases blood alcohol concentrations in humans after ingestion of ethanol. AB - Gastric first-pass metabolism of ethanol is an important determinant of blood alcohol concentrations. We studied five healthy volunteers after ingestion of ethanol (0.3 g/kg of body weight) and found that blood alcohol concentrations in the fed state (ie, 1 hour after a standard breakfast) were significantly higher when the subjects received 1 g of aspirin 1 hour before ingestion of ethanol than without the drug. In vitro, aspirin clearly decreased the activity of gastric alcohol dehydrogenase in human subjects and in rat models, but not that of hepatic alcohol dehydrogenase in rats. Furthermore, blood alcohol concentrations in rats were unaffected by ingestion of aspirin when ethanol was infused intravenously. Thus, aspirin may increase the bioavailability of ingested ethanol in humans, possibly by reducing ethanol oxidation by gastric alcohol dehydrogenase. PMID- 2231998 TI - The federal regulation of prescription drug advertising and promotion. AB - Prescription drug advertising has been regulated by the Food and Drug Administration since 1962. In the past decade, pharmaceutical companies have employed new communication mechanisms to reach physicians and, with increasing frequency, consumers. Examples of physician-oriented promotional activities are medical symposia and teleconferences. Consumer-oriented efforts include press conferences, use of celebrity spokespeople, and direct-to-consumer advertising. The Food and Drug Administration has asserted its legal jurisdiction over these nontraditional promotional activities and is regulating them on a case-by-case basis. As nontraditional promotional efforts become more prevalent, the Food and Drug Administration's regulatory framework must be able to meet the challenges of a changing environment. PMID- 2231999 TI - HIV infection, pregnant women, and newborns: A policy proposal for information and testing. AB - As the public health impact of human immunodeficiency virus (HIV) infection in women and children has increased, so has interest in screening pregnant women and newborns for evidence of HIV infection. However, screening of pregnant women and newborns raises profound moral, legal, and policy issues. In this article, we present and defend a detailed 10-point program of policy recommendations for both pregnant women and newborns. We advocate informing all pregnant women and new mothers about the HIV epidemic and the availability of testing. PMID- 2232001 TI - FDA regulation of prescription drug advertising. PMID- 2232000 TI - A formal audit of continuing medical education activity for license renewal. AB - Formal audits of the continuing medical education activities of physicians licensed in Michigan were undertaken to assess compliance with a law mandating participation in 150 hours of continuing medical education each 3 years. A random sample of all physicians renewing their licenses in 1987 and 1988 were asked to provide documentation of their continuing medical education activities. The average physician participated in 175 hours of category I approved activities; 53.1% of the hours were obtained in a different state, and only 27.6% were obtained in the home community. A total of 13.7% (132/967) of the physicians were initially unable to document 150 hours of credit. Documentation deficiencies and addition errors were found on 72.5% of forms. If formal audits of compliance with legislation are to be undertaken, early notification of the participants and specific instructions for compliance are needed. Because of problems with documentation, only category I approved activities, with exclusions for trainees, should be used to assess compliance. PMID- 2232003 TI - A piece of my mind. View from a room. PMID- 2232002 TI - Continuing medical education at a crossroads. PMID- 2232004 TI - From the Office of the General Counsel. The right to die after Cruzan. PMID- 2232005 TI - Effects of exogenous steroids on basal body temperature. PMID- 2232006 TI - Chronic lower abdominal pain. PMID- 2232007 TI - Persistent open anterior fontanelle. PMID- 2232008 TI - 'Decade of brain' holds promise for answers to schizophrenia. PMID- 2232009 TI - Epidemiology indicates a disorder that assaults much of patients' 'humanness' in prime of life. PMID- 2232010 TI - Controversy grows over monitoring system for new schizophrenia drug. PMID- 2232012 TI - From the Centers for Disease Control. Cigarette smoking cessation--United States, 1989. PMID- 2232011 TI - Psychiatrists increasingly able to assess, treat mental health problems of the very young. PMID- 2232013 TI - Determination of HIV-1 status of discarded sharps: polymerase chain reaction using minute quantities of blood. PMID- 2232014 TI - What matters magnesium? PMID- 2232015 TI - QALYs: their ethical implications. PMID- 2232016 TI - The myth of heterosexual AIDS: a review. PMID- 2232017 TI - The evaluation of hematuria in adults. PMID- 2232018 TI - Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. AB - The prevalence of comorbid alcohol, other drug, and mental disorders in the US total community and institutional population was determined from 20,291 persons interviewed in the National Institute of Mental Health Epidemiologic Catchment Area Program. Estimated US population lifetime prevalence rates were 22.5% for any non-substance abuse mental disorder, 13.5% for alcohol dependence-abuse, and 6.1% for other drug dependence-abuse. Among those with a mental disorder, the odds ratio of having some addictive disorder was 2.7, with a lifetime prevalence of about 29% (including an overlapping 22% with an alcohol and 15% with another drug disorder). For those with either an alcohol or other drug disorder, the odds of having the other addictive disorder were seven times greater than in the rest of the population. Among those with an alcohol disorder, 37% had a comorbid mental disorder. The highest mental-addictive disorder comorbidity rate was found for those with drug (other than alcohol) disorders, among whom more than half (53%) were found to have a mental disorder with an odds ratio of 4.5. Individuals treated in specialty mental health and addictive disorder clinical settings have significantly higher odds of having comorbid disorders. Among the institutional settings, comorbidity of addictive and severe mental disorders was highest in the prison population, most notably with antisocial personality, schizophrenia, and bipolar disorders. PMID- 2232019 TI - Ten-year follow-up of behavioral, family-based treatment for obese children. AB - Using a prospective, randomized, controlled design, we examined the effects of behavioral family-based treatment on percent overweight and growth over 10 years in obese 6- to 12-year-old children. Obese children and their parents were randomized to three groups that were provided similar diet, exercise, and behavior management training but differed in the reinforcement for weight loss and behavior change. The child and parent group reinforced parent and child behavior change and weight loss, the child group reinforced child behavior change and weight loss, and the nonspecific control group reinforced families for attendance. Children in the child and parent group showed significantly greater decreases in percent overweight after 5 and 10 years (-11.2% and -7.5%, respectively) than children in the nonspecific control group (+ 7.9% and + 14.3%, respectively). Children in the child group showed increases in percent overweight after 5 and 10 years (+ 2.7% and + 4.5%, respectively) that were midway between those for the child and parent and nonspecific groups and not significantly different from either. At 10 years, child height was related strongly to the height of the parent of the same sex (r = .78 children were 1.8 cm taller than their parents, with no differences in height between groups. PMID- 2232020 TI - Anaphylaxis following ingestion of a psyllium-containing cereal. AB - Recently, psyllium hydrophilic mucilloid, a bulk-forming laxative, has been added to breakfast cereals for cholesterol-lowering effects. We report a case of a 60 year-old woman with no prior history of psyllium ingestion who developed anaphylactic symptoms after eating a psyllium-containing cereal. Her only previous exposure was dispensing a psyllium-containing laxative as a nurse. Immunoglobulin E-mediated sensitization was documented by skin testing and basophil histamine release. The literature is reviewed regarding allergic reactions to psyllium. Health care workers and pharmaceutical workers handling psyllium may be at increased risk due to sensitization from inhalation. Physicians and consumers should be aware of potential serious reactions from eating psyllium-containing cereals even without prior history of ingestion of psyllium. PMID- 2232021 TI - The diagnosis and management of aortic dissection. AB - Aortic dissection is a severe disease. Most untreated patients with types I and II (proximal) dissection and over half of those with type III (distal) dissection die within 1 year. Most of the deaths occur within 2 weeks and are caused by rupture, aortic insufficiency, and branch vessel obstruction. Aortic dissection is suspected in patients with anterior chest and back pain that progresses downward. Diagnosis is confirmed by computed tomography, aortography, or echocardiography. Appropriate medical treatment and corrective surgery, including total aortic replacement, performed in the acute and chronic stages, are now successful in over 90% of the cases; long-term results of treatment are steadily improving and are expected to exceed 50% at 10 years. The keys to a successful outcome are being aware of the symptoms of dissection, early diagnosis, and prompt application of appropriate treatment; diligent follow-up includes controlling blood pressure, decreasing the velocity of left ventricular contraction, monitoring the size of the residual aorta, and taking appropriate action if redissection, aneurysmal formation, or rupture occurs. PMID- 2232022 TI - The future of psychiatry. Council on Long Range Planning and Development. AB - The American Medical Association Council on Long Range Planning and Development has been publishing a series of reports that assess trends in the environment of medicine and their impact on physicians and health care provision. The Council believes each specialty in medicine will respond differently to changes in the health care arena. This report, developed in cooperation with the American Psychiatric Association, provides an overview and environmental analysis of the specialty of psychiatry. Socioeconomic data pertinent to psychiatry are reviewed first, followed by a review of scientific and clinical developments in the specialty. Next, the changing provision patterns of psychiatric care, the emerging patient populations served by psychiatrists, and recent developments in graduate medical education in psychiatry are reviewed. The Council also addresses changes in the financing of psychiatric care. In conclusion, the Council suggests implications of these and other environmental trends for psychiatry. PMID- 2232023 TI - The progress and prospects of psychiatry. PMID- 2232024 TI - Treatment of obesity in children. PMID- 2232025 TI - Animal rights vs research? A question of the nation's scientific literacy. PMID- 2232026 TI - Diagnostic and therapeutic technology assessment. Dorsal rhizotomy. PMID- 2232027 TI - Synthetic vascular graft trials start; endothelialization seen as possible. PMID- 2232028 TI - Advances in diabetic retinopathy could save sight, money with more frequent eye exams. PMID- 2232030 TI - And some recommend it as a vampire prophylactic. PMID- 2232029 TI - Individualized care, as well as intensive care, may reduce morbidity among premature infants. PMID- 2232031 TI - From the Congressional Office of Technology Assessment. PMID- 2232032 TI - From the Centers for Disease Control. Cigarette brand use among adult smokers- United States, 1986. PMID- 2232033 TI - From the Centers for Disease Control. Analysis of L-tryptophan for etiology of eosinophilia-myalgia syndrome. PMID- 2232034 TI - Free cefixime in community health centers. PMID- 2232035 TI - The diagnosis of pulmonary embolism. PMID- 2232036 TI - HBV, HIV, and the proscription of intercourse. PMID- 2232037 TI - Air sampling for Legionella. PMID- 2232038 TI - The AMA specialty journals: everyone, including grunts, squeals unfair. PMID- 2232039 TI - The efficacy of preemployment drug screening for marijuana and cocaine in predicting employment outcome. AB - We present a prospective, controlled study of the association between preemployment drug screening results and employment outcomes in 2537 postal employees. For identified marijuana users, relative risk for turnover was 1.56 (95% confidence interval [Cl], 1.17 to 2.08); accidents, 1.55 (95% Cl, 1.16 to 2.08); injuries, 1.85 (95% Cl, 1.30 to 2.64); and discipline, 1.55 (95% Cl, 1.03 to 2.32). Their mean absence rate was 7.1% compared with 4.0% for nonusers. For identified cocaine users, relative risk for turnover was 1.15 (95% Cl, 0.65 to 2.05); accidents, 1.59 (95% Cl, 0.95 to 2.67); injuries, 1.85 (95% Cl, 1.01 to 3.39); and discipline, 1.40 (95% Cl, 0.62 to 3.17). Their mean absence rate was 9.8%. Our study shows that a preemployment drug screen positive for marijuana or cocaine is associated with adverse employment outcomes. The level of risk, however, is much less than previously estimated. This finding has important implications for the social, legal, and economic arguments for and against drug testing. PMID- 2232040 TI - Association of group C beta-hemolytic streptococci with endemic pharyngitis among college students. AB - Throat cultures were performed throughout 2 school years to determine whether non group A beta-hemolytic streptococci (NGA BHS) could be isolated more frequently in 232 college students who had symptomatic pharyngitis than from 198 age-matched controls with noninfectious problems. Duplicate throat swabs were inoculated onto plates that contained sheep blood agar, one plate being incubated in a 5% CO2 atmosphere and the other in an anaerobic environment. The BHS were grouped using latex agglutination. Among the NGA BHS, only those from group C were isolated significantly more often among the patients compared with the controls (26% vs 11%). Quantitative colony counts of isolates of group C BHS were generally higher among patients than controls. Patients with group C BHS had fever, exudative tonsillitis, and anterior cervical adenopathy significantly more frequently than did patients who had throat cultures that were negative for group C BHS. Group C BHS were epidemiologically associated with endemic pharyngitis in this college student population. PMID- 2232042 TI - Excess deaths from nine chronic diseases in the United States, 1986. AB - To assess excess mortality from chronic disease in the United States, state age adjusted combined mortality rates for nine chronic diseases in 1986 were compared with three "minimum" rates--two calculated from rates actually achieved in states and a third estimated as the mortality remaining after elimination of one risk factor for each disease. Hawaii had the lowest mortality rate of combined diseases (305/100,000); state excesses ranged from 0% to 37%. The sum of lowest disease-specific rates in any state was 284 per 100,000, indicating excesses of between 7% and 41%. A minimum mortality rate of 224 per 100,000 was estimated to result from elimination of one risk factor for each of the nine diseases, indicating state excesses from 26% to 54%, or 524,000 US deaths. Reduction of US mortality from the nine diseases to the risk factor--eliminated rate is estimated to be associated with an increased life expectancy at birth of 4 years. PMID- 2232041 TI - Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women. AB - We prospectively examined the use of estrogen replacement therapy in relation to breast cancer incidence in a cohort of women 30 to 55 years of age in 1976. During 367 187 person-years of follow-up among postmenopausal women, 722 incident cases of breast cancer were documented. Overall, past users of replacement estrogen were not at increased risk (relative risk, 0.98; 95% confidence interval, 0.81 to 1.18), including even those with more than 10 years since last [corrected] use (relative risk after adjustment for established risk factors, 0.70; 95% confidence interval, 0.45 to 1.10). However, the risk of breast cancer was significantly elevated among current users (relative risk, 1.36; 95% confidence interval, 1.11 to 1.67). Among current users, a stronger relationship was observed with increasing age but not with increasing duration of use. These data suggest that long-term past use of estrogen replacement therapy is not related to risk of breast cancer but that current use may modestly increase risk. PMID- 2232043 TI - Diclofenac-associated hepatotoxicity. AB - Diclofenac sodium, a phenylacetic acid-derived nonsteroidal anti-inflammatory drug (NSAID) recently released in the United States, was associated with the development of significant hepatitis in seven patients, with one associated death. Signs and symptoms developed within several weeks of initiation of drug use and generally resolved 4 to 6 weeks following discontinuation of use of the drug. The only patient rechallenged with the drug developed a recurrence of her hepatic abnormalities. In one patient, fatal, fulminant hepatitis developed despite early withdrawal of the drug. Review of the European literature disclosed three additional fatalities associated with diclofenac therapy. It is unclear whether the incidence of hepatotoxicity is higher with this drug compared with other nonsteroidal anti-inflammatory drugs. Careful patient monitoring is advised, and prompt discontinuation of the drug is suggested when signs or symptoms of liver disease develop. PMID- 2232044 TI - Treatment of speech and voice disorders with botulinum toxin. PMID- 2232045 TI - Preemployment drug screening. PMID- 2232046 TI - Another side effect of NSAIDs. PMID- 2232047 TI - A piece of my mind. The only outlet. PMID- 2232048 TI - Mother to child: first living donor lung transplant. PMID- 2232049 TI - Helicobacter: new name, new hypothesis involving type of gastric cancer. PMID- 2232050 TI - Cold laser, arterial stent studies continue. PMID- 2232051 TI - Gene scene. PMID- 2232052 TI - From the National Institutes of Health. PMID- 2232053 TI - From the Centers for Disease Control. Cigarette sales to minors--Colorado, 1989. PMID- 2232054 TI - Fatal occupational injuries. PMID- 2232055 TI - House staff supervision and working hours. PMID- 2232056 TI - Informed consent and abortion. PMID- 2232057 TI - New approaches for inflammatory bowel disease. PMID- 2232058 TI - Substance abuse and anesthesiology training. PMID- 2232059 TI - Making a complete orthopod. PMID- 2232060 TI - Unbundling: neither canny nor fraud, merely unwitting. PMID- 2232061 TI - Senile lens exfoliation. PMID- 2232062 TI - Primary hypertriglyceridemia with borderline high cholesterol and elevated apolipoprotein B concentrations. Comparison of gemfibrozil vs lovastatin therapy. AB - A common pattern of dyslipidemia is elevated levels of plasma triglyceride, borderline high total cholesterol, reduced high-density lipoprotein, and increased apolipoprotein B. This pattern of dyslipidemia frequently is associated with premature coronary heart disease. Nicotinic acid is the drug of first choice for this pattern. In this study, gemfibrozil and lovastatin were compared for their effects on the overall lipoprotein profile in 13 men with this type of dyslipidemia. Both drugs significantly reduced very-low-density lipoprotein and intermediate-density lipoprotein cholesterol levels, and both modestly raised high-density lipoprotein cholesterol levels. Gemfibrozil therapy, however, failed to reduce total cholesterol or total apolipoprotein B levels, whereas lovastatin therapy lowered levels of total cholesterol by 28%, low-density lipoprotein cholesterol by 33%, and total apolipoprotein B by 32%. Moreover, lovastatin therapy caused greater declines in lipoprotein cholesterol ratios than gemfibrozil therapy. Lovastatin thus seems to have certain advantages over gemfibrozil for treatment of elevated plasma triglyceride levels accompanied by borderline high total cholesterol and raised apolipoprotein B levels; therefore, lovastatin therapy should be considered as one approach for management of this condition. PMID- 2232063 TI - The HIV-testing policies of US hospitals. AB - To determine the human immunodeficiency virus-testing policies adopted by US hospitals, we surveyed a stratified random sample of all nonfederal general acute care hospitals, drawn from the American Hospital Association's 1987 database. Interviews were completed with the chief administrator in 561 hospitals (response rate, 78.4%). Two thirds of hospitals have admitted at least one patient with the acquired immunodeficiency syndrome, and over 83% have formal written policies about human immunodeficiency virus testing. Most contain provisions protecting patients' rights; eg, 78% require pretest informed consent, 66% require a special human immunodeficiency virus-testing consent form, and 75% require that patients who test seropositive be so informed. Many policies also contain provisions that protect providers; eg, 56% require that test results appear in patients' records, 38% require review of treatment plans when a patient tests seropositive, and 3% require transferring such patients. Hospital characteristics are not strongly associated with the adoption of testing policies. PMID- 2232064 TI - Adult open heart surgery in New York State. An analysis of risk factors and hospital mortality rates. AB - This study analyzes data from New York State's new Cardiac Surgery Reporting System, which contains information about cardiac preoperative risk factors, postoperative complications, and hospital discharge. The purposes of the study were to determine the set of significant clinical risk factors and to identify cardiac surgical centers most likely to have serious quality-of-care problems. Significant risk factors for in-hospital death were age, gender, ejection fraction, previous myocardial infarction, number of open heart operations in previous admissions, diabetes requiring medication, dialysis dependence, disasters (acute structural defect, renal failure, cardiogenic shock, gunshot), unstable angina, intractable congestive heart failure, left main trunk narrowed more than 90%, and type of operation performed. Four of the 28 hospitals had significantly higher mortality rates than expected, given the risk factors of their patients. Subsequent site visits and medical record reviews confirmed that these facilities had high percentages of quality-of-care problems among cases resulting in mortality. PMID- 2232065 TI - Bhopal tragedy's health effects. A review of methyl isocyanate toxicity. PMID- 2232067 TI - Treatment choices for hypertriglyceridemia. PMID- 2232066 TI - Public health lessons from the Bhopal chemical disaster. PMID- 2232068 TI - Hyperosmia and depression following exposure to toxic vapors. PMID- 2232069 TI - Why study medical history? PMID- 2232070 TI - Early chapters in the stethoscope's evolution. PMID- 2232071 TI - Curiosities of contraception: a historical perspective. PMID- 2232072 TI - Troubled past of 'invisible' profession. PMID- 2232073 TI - Disease pattern changes with food system. PMID- 2232074 TI - From the Food and Drug administration. PMID- 2232075 TI - From the Centers for Disease Control. Health beliefs, compliance--hypertension. PMID- 2232076 TI - Maternal ginseng use associated with neonatal androgenization. PMID- 2232077 TI - Cystic fibrosis and heterozygote fitness. PMID- 2232078 TI - Endothelin-1 and vasculitis. PMID- 2232079 TI - The effect of extracorporeal shock wave lithotripsy on blood pressure. PMID- 2232080 TI - Fluoxetine and fibromyalgia. PMID- 2232081 TI - Doctors with gilt complex calculate golden means. PMID- 2232082 TI - Radium exposure and longevity: not mutually exclusive. PMID- 2232083 TI - Tubal sterilization and the long-term risk of hysterectomy. AB - To assess the effect of tubal sterilization on the risk of hysterectomy, we studied 7414 women aged 20 to 49 years who had had a tubal sterilization at a health maintenance organization between January 1, 1968, and December 31, 1983. Compared with a population-based cohort of nonsterilized women, women sterilized while 20 to 29 years old were 3.4 times more likely to have had a subsequent hysterectomy (95% confidence interval, 2.4 to 4.7). Adjustment for the effects of potential confounders with a subset of 276 women did not appreciably alter this association. For multivariate comparisons with 5323 wives of vasectomized men, there was no significant elevation in the risk of hysterectomy following sterilization among women sterilized while 20 to 29 years old. Tubal sterilization was not associated with hysterectomy for married women who underwent tubal sterilization at age 30 or older. These results do not support a biological basis for the relationship between tubal sterilization and hysterectomy. PMID- 2232084 TI - A public hospital closes. Impact on patients' access to care and health status. AB - We studied the impact of the closing of a public hospital on patients' access to care and health status. We surveyed individuals who had been medical inpatients at Shasta General Hospital, Redding, Calif, in the year prior to its closing and compared them with those in a second county, San Luis Obispo, whose public hospital did not close. Surveys were administered after the closing of Shasta General Hospital and 1 year later. We assessed outcomes using the Medical Outcomes Study Short Form and a series of transition questions that asked about changes in health over time. Data were available for 88% of patients at 1 year: 219 from Shasta County and 195 from San Luis Obispo County. At follow-up, the percentage of patients from Shasta County who reported no regular provider increased from 14.0 to 27.7 and the percentage who reported they were denied care rose from 10.8 to 16.9. Meanwhile, patients in San Luis Obispo County reported improved access to a regular provider and the level of denied care was unchanged. Patients in Shasta County had significant declines on the Medical Outcomes Study Short Form in health perception, social and role function, and increases in pain as compared with those patients in San Luis Obispo County. The closing of a public hospital had a significant effect on access to health care and was associated with a decline in health status. PMID- 2232085 TI - The epidemiology and natural history of pressure ulcers in elderly nursing home residents. AB - We analyzed prospective data from 19,889 elderly residents of 51 nursing homes from 1984 to 1985 to determine the prevalence, incidence, and natural history of pressure ulcers. Among all residents admitted to nursing homes, 11.3% possessed a stage II through stage IV pressure ulcer. For those residents admitted to the nursing home without pressure ulcers during the study period, the 1-year incidence was 13.2%. This increased to 21.6% by 2 years of nursing home stay. People already residing in a nursing home at the start of the study had a 1-year incidence of 9.5%, which increased to 20.4% by 2 years. Pressure ulcers were associated with an increased rate of mortality, but not hospitalization. Longitudinal follow-up of residents with pressure ulcers demonstrated that a majority of their lesions were healed by 1 year. Most of the improvement occurred early in a person's nursing home stay. Although nursing home residents with pressure ulcers have a higher mortality, with good medical care pressure ulcers can be expected to heal. PMID- 2232086 TI - Pneumococcal vaccine. Efficacy and associated cost savings. AB - We evaluated the efficacy and cost savings of the pneumococcal pneumonia vaccine in a retrospective cohort study of 762 vaccinated and 1161 randomly selected unvaccinated age-sex matched persons in Blue Cross/Blue Shield of Minnesota using medical and pharmaceutical claims. The pneumonia incidence and the ratio of incidence in the postvaccination to prevaccination periods (rate ratio) were examined in the vaccine group by sex and risk factors. Vaccination significantly reduced pneumonia incidence, with overall efficacy of 69% and higher efficacy in women (86%) than in men (33%). We assigned persons to risk categories based on disease conditions as recorded in the claims by the ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnostic codes. In the risk categories, efficacy varied from 50% to 75% and was confounded by sex. Immunocompromised and immunocompetent women had high efficacy (83% to 88%), while immunocompetent and immunocompromised men had lower efficacy (33%). Persons with a precondition of pneumonia exhibited similar vaccine efficacy to the overall cohort relative to the comparison group. Projected costs of pneumonia cases are 3.6 times the observed costs of vaccination and postvaccination pneumonia costs. We conclude that the pneumococcal pneumonia vaccine is efficacious in persons having had pneumonia, persons "at risk" of developing pneumonia, or persons over 50 years of age, and it corresponds to overall savings of $141 per person. PMID- 2232087 TI - Positive Lyme serology in subacute bacterial endocarditis. A study of four patients. AB - Lyme borreliosis is a multisystem inflammatory disorder caused by the tick-borne spirochete Borrelia burgdorferi. Clinical manifestations are protean, involving the skin, joints, peripheral and central nervous systems, and the heart. However, the presentation of Lyme disease often overlaps with that of other conditions. We describe four patients from a region endemic for Lyme disease who had elevated levels of antibodies reactive to B burgdorferi and whose signs and symptoms were initially attributed to Lyme borreliosis but whose subsequent blood cultures established a diagnosis of nonspirochetal subacute bacterial endocarditis. Although immunoblots on serum samples from three of the four patients were consistent with prior infection from B burgdorferi, a positive immunoblot does not establish active infection. Similarly, seropositivity to B burgdorferi only indicates possible exposure to this organism. The occurrence of positive serologies to B burgdorferi in the presence of other diseases can lead to diagnostic confusion. PMID- 2232088 TI - Medical and nonmedical uses of anabolic-androgenic steroids. Council on Scientific Affairs. AB - Recent trends in the use, abuse, and diversion of steroids for nonmedical purposes illustrate a growing problem that not only imposes health risks but presents ethical dilemmas as well. Concern over the known adverse effects, the limited research into the long-term effects, and the ethics of engineering body size and performance through anabolic-androgenic steroid use has led to legislative, legal, and education responses. Increased penalties for distribution to minors and stricter controls in prescribing practices have been enacted through state legislation and federal initiatives. Government, some health professional organizations, and some sports groups have denounced the nonmedical use of anabolic-androgenic steroids and have developed materials to educate their members, other professionals, athletes, educators, and the public at large. PMID- 2232089 TI - A multicenter study of physicians' knowledge of the pulmonary artery catheter. Pulmonary Artery Catheter Study Group. AB - We administered a 31-question multiple-choice examination to 496 physicians practicing in 13 medical facilities in the United States and Canada to assess their knowledge and understanding of the use of the pulmonary artery catheter and interpretation of data derived from it. The mean test score was 20.7 (67% correct), with an SD of 5.4 and a range of 6 to 31 (19% to 100%). Mean scores varied independently by training, frequency of use of pulmonary artery catheter data in patient treatment, frequency of inserting a pulmonary artery catheter, and whether the respondent's hospital was a primary medical school affiliate. Given the variability in physician understanding of the pulmonary artery catheter, we believe that credentialing policies should be reevaluated and that consideration should be given to restricting its use to individuals with documented competency. PMID- 2232090 TI - High-tech predicament: pulmonary artery catheter. PMID- 2232091 TI - Preincubation with intravenous lipid emulsion reduces chemotactic motility of neutrophils in cord blood. AB - Neutrophils from cord blood of healthy term infants were isolated and incubated for 30 min with varying concentrations of intravenous lipid emulsion (ILE) solution (4, 8, 20 mg/ml). In vitro assay of chemotaxis was performed after incubation for 120 min with endotoxin-activated serum (EAS). Neutrophil random motility was unchanged after ILE incubation yet chemotactic factor (EAS) stimulated motility was significantly reduced in a dose-related pattern. PMID- 2232092 TI - Protein metabolism assessed by 1-13C leucine infusions in patients undergoing bone marrow transplantation. AB - Patients receiving cytoreductive therapy and bone marrow transplantation (BMT) are known to develop marked protein catabolism. To assess the contribution of whole body protein breakdown, amino acid oxidation and incorporation into proteins, plasma leucine kinetics (1-13C-leucine infusion technique) were determined in six patients five times within 14 days before and after cytoreductive therapy (Cyclophosphamide and total body irradiation) and marrow transplantation. Nitrogen balance became negative (-0.20 +/- 0.04 g/Kg/24 hr) after cyclophosphamide (p less than 0.01) and was -0.25 +/- 0.05 g/Kg/24 hr 7 days after BMT in spite of total parenteral nutrition. Plasma leucine concentration increased after BMT by 67% (p less than 0.0015). Leucine plasma appearance was 1.20 +/- 0.15 mumol/kg/min before treatment, it increased slightly and transiently after cyclophosphamide, and increased again from day 5 to day 7 after BMT (p less than 0.01), suggesting increased protein break-down. Leucine oxidation increased from 0.27 +/- 0.07 before therapy to 0.97 +/- 0.16 mumol/kg/min (p less than 0.02) after cyclophosphamide and BMT. Nonoxidative leucine disappearance rate decreased slightly from 0.92 +/- 0.08 to 0.75 +/- 0.16 mumol/kg/min after BMT (ns). Leucine metabolic clearance rate decreased from 11.8 +/- 1.65 before therapy to 6.9 +/- 0.70 ml/kg/min (p less than 0.02) after cytoreductive therapy. After BMT it increased again to 9.9 +/- 1.5 ml/kg/min (p less than 0.02). The results demonstrate that patients undergoing cytoreductive therapy and bone marrow transplantation develop negative nitrogen balance due to increased protein breakdown associated with increased leucine oxidation and increased metabolic clearance rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232094 TI - Rapid spectrophotometric determination of plasma carnitine concentrations. AB - A spectrophotometric enzymatic assay for plasma carnitine concentrations has been automated on the Monarch 2000. Prior to the assay, each plasma sample was divided into three fractions, ie, free carnitine, acid-soluble carnitine and total carnitine, in order to determine the concentration of both free and esterified carnitine. Using the method developed by Tachikawa et al (Seikagaku 56:998, 1984), each of the samples was then chromatographed on an anion exchange resin to eliminate those compounds which could adversely impact the accuracy of the enzymatic assay for carnitine. After the completion of these preparatory steps, 32 specimens were assayed in less than 16 min on the Monarch 2000 with a high degree of both accuracy and precision. The assay was linear over a wide concentration range (5.0-80 mumol/liter), with the lower limit of sensitivity being 5.0 mumol/liter. The coefficient of variation (CV%) of the within run precision was 2.1%, 2.8%, and 6.7% for the determinations of free carnitine, acid soluble carnitine, and total carnitine, and 17.4% and 27.8% for the calculated values of short-chain and long-chain acylcarnitines, respectively. The CV% of the between run precision for the same fractions was 6.5%, 2.7%, 3.8%, 14.2%, and 14.3%, respectively. When authentic L-carnitine was added to the plasma, the mean recovery rate was 94.7 +/- 11.0%. Reference values were determined using plasma obtained from 40 healthy adult volunteers. PMID- 2232093 TI - Comparison of three methods for the estimation of total nitrogen losses in hospitalized patients. AB - Since the measurement of total nitrogen output (TNO) is not routinely determined in the clinical setting, its level is frequently estimated using formulas based on the urinary urea nitrogen excretion (UUN). We measured TNO in 124 surgical patients over 990 days (TNO, 19.22 +/- 8.72 g N/day; total urinary nitrogen (TUN) 18.17 +/- 8.70 g N/day; UUN, 15.17 +/- 7.70 g N/day; mean gastrointestinal nitrogen (MGIN) 0.68 +/- 0.49 g N/day; integumental nitrogen (ITGN), 0.34 +/- 0.08 g N/day) and compared the results with the daily estimations using three different formulas: formula A, UUN + 4; formula B, UUN x 1.20 + 1.05, where 1.20 is the reciprocal of the mean ratio UUN/TUN and 1.05 the mean extraurinary nitrogen losses; and formula C, UUN x 1.0986 + 2.55, derived from the regression analysis of UUN vs TNO. TNO estimated by these formulas were 19.17 +/- 7.70, 19.26 +/- 9.24, and 19.22 +/- 8.70 g N/day, respectively. The regression analyses of the estimated TNO from the three formulas versus the measured TNO indicated that formulas A, B and C were equally accurate in estimating TNO over the entire range of UUN. However, when only values of UUN greater than or equal to 30 g N were considered, a modified formula A (UUN + 6) was the best predictor of TNO. Daily audits of the differences between the estimated and measured TNO showed comparable results for the three formulas. In 28.4 to 31.1% of the observed days the differences were higher than +/- 2 g N/day, an error which is not acceptable when estimating the protein requirements in many clinical conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232095 TI - Is exogenous fructose metabolism truly insulin independent? AB - Although fructose is widely regarded as an insulin-independent fuel source, its in vivo conversion to glucose represents a theoretical limitation to its clinical usefulness in diabetics, particularly if given in large doses. To determine whether small amounts of fructose can be well utilized in the setting of insulinopenia, we administered a low-dose fructose infusion (4.2 g/hr) to a fasting type 1 diabetic patient receiving continuous subcutaneous insulin at a dose that had previously maintained stable euglycemia for 72 hr (plasma glucose = 80-110 mg/dl). Despite the low infusion rate (less than 20% of calorie requirement), fructose caused an immediate and marked rise in plasma glucose (to 370 mg/dl after 27 hr). Glucose loss in the urine and accumulation in plasma could account for fully half of the administered hexose load. Thus, the utilization of even small quantities of exogenous fructose is profoundly impaired under hypoinsulinemic conditions. It is misleading to regard fructose as a truly insulin-independent fuel source. PMID- 2232096 TI - Resting energy expenditure in patients with esophageal carcinoma. PMID- 2232098 TI - Clinical biochemistry: implications for nutritional support. PMID- 2232097 TI - No short cuts to height. PMID- 2232099 TI - What getting sick means. AB - The concepts of health, disease and death have intrigued man since the beginning of time and are continually evolving. In the nonwestern societies the models which have been proposed for the etiology of disease have a dichotomous view of disease causation which is derived from either natural or supernatural forces. In the Western societies these concepts are well defined. The numerous advances in the fields of genetics and molecular biology have added a new dimension to the understanding of the various factors involved in the pathogenesis of disease processes. These advances have allowed a greater understanding of numerous disease processes including the inborn errors of metabolism, endocrine disorders and human neoplasia. Several recent advances in the areas of molecular biology and physiology allowing this increased understanding of human disease are presented. PMID- 2232100 TI - How nutrition intervention changes what getting sick means. PMID- 2232101 TI - Kupffer cell and hepatocyte interactions: a brief overview. PMID- 2232102 TI - Metabolic and intestinal effects of short-chain fatty acids. AB - Current research has identified the metabolic and intestinal effects of SCFA in experimental models and humans. Ample physiologic rationale has come forth to justify controlled studies of the administration of SCFA in selected patients with intestinal dysfunction. PMID- 2232103 TI - Perioperative nutritional support: immunologic defects. PMID- 2232104 TI - Assessment of nutritional status. PMID- 2232105 TI - Lipids, membrane receptors, and enzymes: effects of dietary fatty acids. AB - Dietary polyunsaturated fatty acids can significantly affect many biochemical and physiologic functions that are related to inflammatory, immune, and protective reactions. The different types of fatty acids can impact on energy metabolism, determine the lipid composition of membranes, and influence eicosanoid synthesis, all of which are relevant to prevention of and recovery from illness. In this paper, the effects of dietary polyunsaturated fatty acids on membrane composition, membrane-associated enzyme and receptor functions, signal transduction, second messenger, and eicosanoid generation are summarized. The differential effects of the polyunsaturated fatty acids of the n-6 and n-3 families are reviewed in the context of optimizing levels in diets. PMID- 2232106 TI - Practicalities of lipids: ICU patient, autoimmune disease, and vascular disease. AB - Although the use of lipids should be individualized, certain generalizations are appropriate. 1. Lipid infusion should be limited in the fulminately septic patient to 10% of total calories in an effort to reduce immunosuppression. 2. The stressed, nonseptic patient with difficulties in ventilator weaning or TPN induced hepatic dysfunction may reap benefit from a reduction in dextrose calories and the provision of daily lipids. 3. Patients with severe autoimmune disease have had mild amelioration of symptoms with PUFA supplementation. The relative benefits of omega-6 vs omega-3 continue to be examined. 4. Dietary immunomodulation in transplant and burns remains an area of active investigation. 5. Patients with fat-free TPN show transient declines in serum lipids. The development of a "fat-solubilizer" remains in the experimental realm. 6. The provision of fish oil, high in W-3 EPA, has shown promise in atherosclerosis and immunomodulation. The changes in the relative amounts of each prostaglandin class depend on precursor prevalence. PMID- 2232107 TI - Role of arginine in trauma, sepsis, and immunity. PMID- 2232108 TI - Influence of energy levels and trace metals on health and life span. PMID- 2232110 TI - Left ventricular filling pattern in congestive heart failure patients with normal sinus rhythm--a decreased ratio of peak mitral flow velocity in atrial systole relative to that in early diastole may reflect markedly increased left ventricular end-diastolic pressure. AB - The left ventricular filling pattern was studied by pulsed Doppler echocardiography in 13 congestive heart failure patients with normal sinus rhythm. The first study was done when congestive heart failure was present; the second after the signs and symptoms of congestive heart failure disappeared. In 12 of the 13 patients, the peak mitral flow velocity in atrial systole (PFVA) increased after the congestive heart failure disappeared (mean increase from 50.5 cm/sec to 74.8 cm/sec : p = 0.0001, paired t test), and the peak mitral flow velocity in early diastole (PFVE) decreased significantly in all 8 patients in whom secondary mitral regurgitation became less severe after improvement of congestive heart failure (mean decrease from 90.8 cm/sec to 52.0 cm/sec : p = 0.0001, paired t test). The ratio of PFVA to PFVE (PFVA/PFVE) increased in all cases after the congestive heart failure improved (mean increase from 0.59 to 1.33 : p = 0.0001, paired t test). The PFVA/PFVE is a simple index of left ventricular diastolic function. A PFVA/PFVE greater than one indicates disturbed left ventricular diastolic function. However, when the PFVA/PFVE is in a normal range for the patients' age ("pseudo-normalization") and is accompanied by impaired left ventricular systolic function in congestive heart failure, markedly increased left ventricular end-diastolic pressure must be considered. PMID- 2232109 TI - Glutamine nutrition: theoretical considerations and therapeutic impact. AB - In critically ill surgical patients, nutritional therapy is an important component of overall care. As our knowledge increases, "tailor-made" diets designed to meet specific nutritional requirements in specific patients may play an important role. Although the data reviewed here suggest that glutamine supplemented diets may have a significant impact in some clinical settings, it should be emphasized that additional carefully designed studies are necessary before the use of glutamine-enriched nutrition in critically ill patients should be advocated. It is clear, however, that the concept that the intestine is an organ of inactivity during critical illness merits reconsideration. PMID- 2232111 TI - Kinetic analyses of creatine kinase release patterns in patients with acute myocardial infarction undergoing emergency coronary arteriography. AB - To quantify the effects of early reperfusion on the size of infarcts, an enzyme indicator was developed: myocardial creatine kinase (CK) release rate (kr), based on a compartmental kinetics model. In 59 patients with acute myocardial infarction (MI) who received intracoronary thrombolysis therapy in the acute phase, the kr showed a good correlation with the flow condition of infarct related coronary artery and the time required to reach peak enzyme activity. Apparent serum CK disappearance rate (kd') was estimated by using the method of Norris. The kd' was significantly underestimated in patients without reperfusion, suggesting the presence of prolonged enzyme release from the infarcted area. In 22 of 59 patients, who had a first acute anterior MI (left anterior descending arterial lesion), the correction of cumulative enzyme release by myocardial enzyme release (kr) resulted in a closer correlation with chronic phase left ventricular function. Thus, kinetic analyses of serum enzyme release provide a useful means to estimate the infarct size during intracoronary thrombolysis therapy. PMID- 2232112 TI - Treatment of unstable angina with cholesterol embolization as a complication of left heart catheterization. AB - We describe 3 patients with cholesterol embolization after left heart catheterization via the femoral route. The left catheterizations were performed via the femoral route in all reported cases in which cholesterol embolization occurred as a complication of left catheterization. Postmortem examinations reveal that PTCA, using the right brachial approach, is the safest method for treatment of intractable angina in patients with evidence of cholesterol embolization. PMID- 2232113 TI - Metabolic risk factors in the normolipidemic male patients with angiographically defined coronary artery disease. AB - The relationship of plasma lipid and apolipoprotein (apo) concentrations and plasma insulin response to oral glucose load to angiographically determined coronary artery disease (CAD) was investigated in 65 normolipidemic (plasma cholesterol less than 230 mg/dl and plasma triglyceride less than 150 mg/dl) males. According to the results of coronary angiography, the patients were divided into 2 groups: patients with normal coronary artery, NCA group (n = 21); and patients with coronary artery disease, CAD group (n = 44). No significant differences in concentrations of plasma cholesterol and triglyceride were observed between the CAD and NCA groups. In the CAD group cumulative lifetime tobacco consumption was higher and high density lipoprotein (HDL) cholesterol concentration was lower than those in the NCA group. The variables that correlated with the severity of CAD, defined by the number of lesions and percent stenosis, were levels of plasma apo A-I and apo B. Prevalence of subjects with reduced oral glucose tolerance did not differ between 2 groups. However, hyperinsulinemic response to oral glucose load was present in the CAD group. HDL cholesterol concentration, the sum of plasma insulin levels and the magnitude of the early insulin response during oral glucose challenge were accurate predictors of the presence of but not the severity of CAD. Multivariate analysis of the data confirmed the independent effect of plasma levels of apo A-I and apo B on the severity of CAD. The present data indicated that plasma levels of apo A-I and apo B were powerful discriminators in the normolipidemic CAD patients and that a high insulin response might be an indicator of enhanced susceptibility to the distinct coronary atherosclerosis. PMID- 2232114 TI - Changes in vascular wall production of prostacyclin and thromboxane A2 in spontaneously hypertensive rats during maturation and the concomitant development of hypertension. AB - The purpose of this study was to clarify how the metabolism of vascular prostacyclin (PGI2) and thromboxane (TX) A2 in spontaneously hypertensive rats (SHR) is involved in aging and development of hypertension. We removed the aortic walls from 5-week-old and 20 to 25-week-old SHR and age-matched Wistar Kyoto rats (WKY). At 5 weeks of age, there was no significant difference in basal and maximal (arachidonic acid 0.1 mM) 6-keto-PGF1 alpha production between SHR and WKY, but the TXB2 generation in the SHR aortic wall was markedly enhanced as compared with that in WKY. At 20 to 25 weeks of age, the SHR aortic wall synthesized about 1.5 times more 6-keto-PGF1 alpha in the basal condition and twice as much as in the maximal condition as did the WKY wall. However there was no significant difference in TXB2 production between SHR and WKY. Age-dependent increase of vascular 6-keto-PGF1 alpha was greater in SHR than in WKY. Moreover, the maximal/basal 6-keto-PGF1 alpha production ratio increased with age in SHR, but not in WKY. The synthesis of vascular TXB2 was enhanced with age in WKY, but did not change with age in SHR. These data suggest that not only the enhanced basal generation of vascular 6-keto PGF1 alpha but also a much greater reservoir of 6-keto-PGF 1 alpha synthesis in SHR was induced by both hypertension and maturity. The increased production of vascular TXB2 in young SHR may affect the development of hypertension. PMID- 2232115 TI - The Mikamo lecture. Role of higher nervous activity in sudden cardiac death. AB - The brain receives and catalogues myriads of information from within and without the organism. These inputs promote neural integration of bodily function through a multiplicity of cybernetic feedback loops. Higher nervous activity shapes the contours of perceived well-being and determines the course and progress of disease. Behavioral and neural factors play an important role in cardiovascular function and are especially relevant to the problem of sudden cardiac death (SCD). Clinical data attesting to the role of biobehavioral factors in SCD derive from a diversity of sources. It has long been known that bereavement increases the prevalence of cardiac fatality. Business failure rates are strongly related to increased mortality among persons aged 55 and over. Recession in economic activity, with increasing unemployment, is associated with augmented death rates from ischemic heart disease. In extensive surveys conducted among London civil servants, Rose and Marmot found not only the level but the type of employment to be a factor determining coronary heart disease mortality. Blue collar workers had a 3.6 times greater chance of dying from heart disease than an age-matched population in the higher ranks of civil service. A man's employment status was a stronger predictor of risk for dying from coronary heart disease than any of the usual risk factors, such as smoking, blood pressure, height-weight ratio, leisure time activities, glucose tolerance, or plasma cholesterol. Operation of behavioral factors is also suggested by the time of occurrence of sudden death. Among 3,983 men followed for more than 30 years, Rabkin and co-workers observed an excess proportion of fatalities on Mondays. No such pattern was noted for cancer mortality. Not only the day of the week but the time of day appears to be a factor. Muller and co-workers found a significant preponderance in the occurrence of myocardial infarction and sudden death from 6:00 AM to noon. They could not implicate operation of circadian rhythm, but suggested a role for augmented autonomic neural discharge associated with early morning activities following waking from sleep. The longitudinal epidemiologic studies of the Health Insurance Plan of New York (HIP) have indicated an important association between behavioral and psychologic factors and the prevalence of sudden cardiac death.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2232116 TI - Afterload mismatch in patients with hypertrophic nonobstructive cardiomyopathy. AB - To investigate the cardiac reserve of hypertrophic nonobstructive cardiomyopathy (HNCM), an echocardiographic study was performed before and during angiotensin II loading in 22 HNCM patients without left ventricular (LV) systolic dysfunction at rest and 8 normal subjects. LV end-diastolic dimension (LVDd) and time velocity integral (Ie) at aortic annulus were obtained as parameters of preload and forward ejection respectively. Responses of these indices to afterload stress were compared with clinical findings and right ventricular biopsy findings. Based on the reserve of forward ejection characteristics to afterload stress, 22 HNCM patients were divided into 2 groups; Group I: 9 cases with more than 15% decrease of Ie which corresponded to the value of mean - 1SD in normal subjects, Group II: 13 cases with a decrease of Ie less than 15%. There were no significant differences in echocardiographic findings between Group I and II before angiotensin II loading. On the other hand, Group I had a smaller increase of LVDd (p less than 0.05) to afterload stress, a higher incidence of ventricular tachycardia on a Holter electrocardiogram (p less than 0.05), lower maximal oxygen consumption with treadmil exercise test (p less than 0.01), and a larger value of LV end-diastolic pressure (p less than 0.05) than those in Group II, respectively. Although no difference in myocyte diameter was found between the 2 groups, myocardial fibrosis was more severe (p less than 0.001) and the incidence of moderate or severe disarray was higher (p less than 0.05) in Group I than in Group II. Thus, some HNCM patients cannot maintain forward ejection to afterload stress because of impaired preload reserve attributable to a greater stiffness of the left ventricle with severe myocardial lesion. PMID- 2232117 TI - Global and regional diastolic filling dynamics in compensated dilated cardiomyopathy. AB - To assess the left ventricular (LV) global and regional (anterior, apical, inferior) diastolic filling dynamics in compensated dilated cardiomyopathy (DCM), we measured left ventricular pressure and instantaneous volume from angiography in 7 normal controls (CTL) and 6 DCM patients with sinus rhythm. Global and regional peak filling rate (PER), time constant of LV pressure decline (T; Weiss's method) and LV chamber stiffness (k; Gaasch's method) were calculated. In DCM, left ventricular end-diastolic volume (ml/m2) was larger than in CTL (137 +/ 29 vs. 74 +/- 6, p less than 0.001), and stroke index (ml/m2) was not different from CTL (46 +/- 14 vs. 46 +/- 8, NS), indicating a compensated state of LV. Mitral valve opening pressure (mmHg) tended to increase in DCM compared with CTL (12 +/- 6 vs. 8 +/- 4). Global PFR (ml/sec/m2) (CTL = 216 +/- 47 vs. DCM = 201 +/ 36) and k (CTL = 0.044 +/- 0.023 vs. DCM = 0.029 +/- 0.016) were not different between 2 groups. However, T (msec) was markedly prolonged in DCM compared with CTL (61 +/- 10 vs. 35 +/- 5, p less than 0.001). In CTL, regional PFR (1/sec) showed almost the same values in each region, but in DCM, apical region showed higher PFR than in other regions. Thus, early diastolic filling might play an important role in maintaining the total transmitral flow in DCM despite severe impairment of LV relaxation. This compensation could be related mainly to accelerated regional lengthening of the LV apical region. PMID- 2232118 TI - Hematoma of the interatrial septum associated with complete atrioventricular block. AB - A 70-year-old man who had been treated for tongue cancer began to suffer from repeated syncopal attacks. His electrocardiogram indicated complete atrioventricular block. A permanent pacemaker was implanted. He was well for about 2 years after which time he developed dyspnea, suffered from general fatigue, and then suddenly died. A postmortem examination revealed a hematoma approximately 4 x 4. cm in size in the interatrial septum, connected to a noncoronary sinus and rupture of the noncoronary leaflet, which compressed the tricuspid and aortic valves. This hematoma might have been related to the conduction disturbance caused by destructive compression on the conduction system, and his death by the rupture of the noncoronary leaflet. PMID- 2232120 TI - Arrhythmia after the release of inhibited oxidative phosphorylation. AB - Automaticities due to delayed afterdepolarizations, elicited upon reoxygenation, are thought to be caused by Ca overload. Since tissue Ca uptake upon reoxygenation has been reported to be closely related to metabolic inhibition during hypoxic perfusion, the relationship between the degree of metabolic inhibition during hypoxia and reoxygenation-induced arrhythmias was investigated in guinea pig papillary muscles. (1) Arrhythmias occurred after 60 min substrate free hypoxia, but not after 30 min hypoxia. The chance of automaticities was closely related with the increase in resting tension achieved during hypoxic period. The incidence of arrhythmias was, however, lower after 90 or 120 min hypoxia. (2) There were arrhythmias after 20-30 min hypoxia with glycolytic inhibition (20 mM 2-deoxyglucose + 5 mM acetate). On the other hand, 60-min hypoxia in the presence of 5 mM glucose did not elicit arrhythmias on reoxygenation. (3) Stimulation of glycolysis (50 mM glucose) during substrate free hypoxia prolonged the action potential duration, but did not cause arrhythmias. Washout of cyanide (1 mM) after 60 min perfusion in the presence of oxygen, caused arrhythmias and aftercontractions. These results suggest that the degree of metabolic inhibition during hypoxia is closely related to Ca overload and the resultant arrhythmias upon reoxygenation. The release of inhibited oxidative phosphorylation, rather than the reintroduction of oxygen per se, was thought to be the key mechanism of reoxygenation-induced arrhythmias. PMID- 2232119 TI - Stroke-prone spontaneously hypertensive rats as a model for toxemia of pregnancy and aggravating and preventive effects of maternal modifications during pregnancy on offspring's growth. AB - Genetical differences in changes in blood pressure (BP) were chronologically investigated during pregnancy in stroke-prone spontaneously hypertensive rats (SHRSP), Wistar-Kyoto rats (WKY) and Sprague-Dawley (SD) rats. Especially, the early stages were carefully studied. Maternal conditions in SHRSP were modified by the treatments with NaCl and taurine, respectively. BP in SHRSP and WKY rose significantly at the early stage of pregnancy compared to prepregnancy levels (SHRSP; 208 +/- 2 mmHg vs 197 +/- 5 mmHg, WKY; 133 +/- 2 mmHg vs 126 +/- 1 mmHg) (p less than 0.05). In contrast, no such changes were observed in SD rats. Differences in 24-hour urinary epinephrine excretion before and during pregnancy ran parallel with such BP changes among these strains. NaCl-loaded SHRSP died during pregnancy with severe pathohistological changes in their kidneys and severe proteinuria. Taurine treatment had a marked prophylactic effect on these maternal pathological changes during pregnancy, resulting in better growth in offsprings. These results suggest that SHRSP could be one of the suitable animal models for the studies on toxemia of pregnancy and also suggest an important role of hypertensive genetical disposition in the development of toxemia of pregnancy. PMID- 2232121 TI - Field emission scanning electron microscopic study on the noninfarcted myocardium after myocardial infarction. AB - Intracellular membranous ultrastructural changes in the noninfarcted myocardium of the left ventricle were studied by examining experimental myocardial infarction in rats with a field emission scanning electron microscope. The left coronary artery was ligated at its origin for 7 days. The resulting infarcts comprised approximately 40% of the total area of the left ventricles. In a light microscopic study, the transverse diameter of myocytes had increased to 17.1 +/- 2.9 microns in the noninfarcted myocardium, compared to 14.1 +/- 3.1 microns in the myocardium of sham-operated rats (p less than 0.01). For the scanning electron microscopic study, the specimens were processed according to the Osmium DMSO-Osmium method. Marked morphological changes of intracellular membranous structures were found in the noninfarcted myocardium, especially in the lacelike network of sarcoplasmic reticulum which occasionally formed large flattened cisternae, and in the marked proliferation of surface caveolae. It is speculated that these early ultrastructural changes in the noninfarcted myocardium reflect an adaptation of microorganellae in the failing hearts of the rats. PMID- 2232123 TI - Proceedings of the 54th Annual Scientific Meeting of the Japanese Circulation Society. March 1990, Fukuoka. Abstracts. PMID- 2232122 TI - Some enzyme characteristics of spontaneously hypertensive rats myocardium. AB - In order to ascertain the pathogenesis of myocardial cell vulnerability in spontaneously hypertensive rats (SHR), several enzyme activities were examined by using subcellular fractions of myocardium and compared to those in Wistar-Kyoto rats (WKY). In the normotensive WKY heart, both 5'-nucleotidase and Na+/K(+) ATPase, which are plasma membrane associated enzymes, increased with age. But in the SHR heart, both enzymes were lower at 16 weeks than they were at 10 weeks of age. Moreover, at 16 weeks of age they were lower in SHR than in WKY. On the other hand, NADP(+)-isocitrate dehydrogenase activity, a mitochondria associated enzyme, was higher in SHR than in WKY at 6 weeks, but lower at 10 and again at 16 weeks of age. The activities of both acid phosphatase and N-acetyl-beta glucosaminidase, which are lysosomal enzymes, decreased with age in SHR but not in WKY. These results suggest that an enzymatic alteration in the plasma membrane and mitochondria may be one of important factors behind myocardial vulnerability in the SHR heart. PMID- 2232124 TI - Chromium, nickel and welding. PMID- 2232125 TI - [Diuretic effects of aminophylline in patients after cardiac surgery]. AB - Diuretic effects of aminophylline in patients after cardiac surgery were studied by using the local renal thermodilution catheter (Goodman Co. Ltd.). The subjects were 11 patients who underwent cardiac surgery in our hospital. All patients had shown almost normal renal and endocrine function. On the day of operation, we indwelld renal thermodilution catheter into the left renal vein under fluoroscopy. After operation, when the urinary volume decreased below 1 ml.kg 1.hr-1, we administered aminophylline at a rate of 2 ml.kg-1.hr-1. We measured HR, BP, CO, PAP, CVP, renal blood flow, urinary volume, urinary electrolytes, plasma renin activity, angiotensin II, aldosteron, ADH and alpha hANP just before and after infusion of aminophylline. The urine volume, renal blood flow and renal blood flow distribution rate showed significant increases of about 70%, 40% and 35% respectively. But hemodynamic parameters including HR, mean BP and CO increased for 5%, 10% and 8% respectively after administration of aminophylline. In the endocrine system, only angiotensin II increased significantly but aminophylline did not cause any change in endocrine system. The results suggest that diuretic effect of aminophylline is mainly achieved by increasing renal blood flow. PMID- 2232126 TI - [Reversal of high-dose fentanyl anesthesia by naloxone]. AB - The EEG, respiratory and hemodynamic responses to postoperative reversal by naloxone of high-dose fentanyl anesthesia were studied in 20 patients (17 cardiac and 3 non-cardiac surgeries). In power spectrum analysis of EEG, power of delta band markedly decreased after naloxone drip infusion. Respiratory and hemodynamic responses were minimum, but increase in HR by 6.4 +/- 9.2 bpm, increase in diastolic BP by 5.3 +/- 9.6 mmHg, and decrease in CVP by 1.9 +/- 2.9 mmHg were statistically significant. Emergence of pain was also minimum and severe side effect was not observed. Reversal of high-dose fentanyl anesthesia by naloxone can reduce the incidence of postoperative respiratory depression and enables early extubation. PMID- 2232127 TI - [Ventilatory effects of halothane and enflurane in dogs]. AB - The ventilatory effects of halothane and enflurane were studied in permanently tracheostomized dogs at the same anesthetic depth of 1 MAC. Inspiratory and expiratory durations were longer and tidal volume greater during enflurane than during halothane anesthesia. Mean inspiratory flow rate and minute ventilation during enflurane anesthesia were less than those during halothane anesthesia. As a result, end-expiratory carbon-dioxide concentration was higher during enflurane than during halothane anesthesia. When end-expiratory carbon-dioxide concentration was held at 7.5%, tidal volume was not different between the two anesthetics, while the difference of other parameters still remained. In addition, the magnitude of Hering-Breuer reflex determined by end-expiratory airway occlusion was essentially identical between halothane and enflurane anesthesia. The present results indicate that 1) depressant effect of enflurane on respiratory drive is greater than that of halothane and 2) the two anesthetics act on the respiratory timing mechanism differently. PMID- 2232128 TI - [Apnea and oxygen desaturation following nitrous oxide inhalation]. AB - Apnea and desaturation following nitrous oxide inhalation were studied in seven adult volunteers breathing spontaneously. Arterial oxygen saturation (SpO2), end tidal CO2 concentration in the nasal cavity and respiratory patterns were measured in volunteers breathing air after N2O (50% or 67%) + O2. SpO2 was measured with Biox 3700 and end-tidal CO2 concentration was measured with Normocap, and respiratory patterns were recorded with RESPIGRAPH. After breathing N2O, two volunteers had frequent apnea (greater than 20 sec) accompanied by desaturation (SpO2 less than 90%). The lowest value of SpO2 was 82%. When the apnea occurred, the airway seemed to be open and end-tidal CO2 concentration values were lower than those before N2O inhalation. The authors considered that this kind of apnea was due to several factors, such as hypocapnia caused by hyperventilation during N2O anesthesia, dilution of alveolar O2 and CO2 during N2O excretion, loss of consciousness by N2O, and depression of CO2 ventilatory response by N2O. Inhalation of O2 at high concentrations for five minutes could improve the hypocapnia and prevent the apnea. PMID- 2232129 TI - [The effects of ulinastatin on the release of granulocyte elastase during pancreas surgery]. AB - During a major abdominal surgery, intraoperative manipulation may cause circulatory changes, which lead to release of granulocyte elastase. Twenty one patients were studied to elucidate the release of granulocyte elastase and the inhibitory effect of a protease inhibitor (ulinastatin) on lysosomal enzyme release during pancreas surgery. Patients were divided into 3 groups. Patients in group A served as control. Patients in group B were given ulinastatin 10,000 units.kg-1 intravenously prior to surgery. Patients in group C were given ulinastatin 5,000 units.kg-1 intravenously twice prior to surgery and 3 hours after the start of surgery. The granulocyte elastase was measured by commercially available kits, at 7 points: prior to induction of anesthesia, immediately after tracheal intubation, 30, 60, 120, 180 min after the start of surgery and 30 min after surgery. The plasma level of elastase increased markedly during the operation in group A, it did not increase in groups B and C during the operation. Thirty min after the operation, the plasma level of elastase increased markedly in group A (354 +/- 63 micrograms.l-1), and in group B (396 +/- 167 micrograms.l 1). The plasma level of elastase was restored to normal levels 30 min after the operation in group C. These results indicate that granulocyte elastase values were maintained at significantly higher levels during and after pancreas surgery, and suggest that ulinastatin inhibits the release of granulocyte elastase during pancreas surgery. PMID- 2232130 TI - [Anesthetic experience of a patient for splenectomy with severe liver dysfunction and hyperammonemia]. AB - A case of a patient with severe liver dysfunction and hyperammonemia undergoing splenectomy and liver biopsy was reported. Preoperative examination revealed that this patient's liver function was severely impaired due to liver cirrhosis (ICG15 = 60%, HPT = 29%, serum NH3 = 110 micrograms.dl-1). Preoperatively, kanamycin 2 g.day-1 and lacturose 60 ml.day-1 were given and FFP 3-5 units.day-1 were infused. With no premedication, general anesthesia was induced with dTc 3 mg, thiopental 200 mg and SCC 80 mg. Anesthesia was maintained with N2O-O2-enflurane and pancuronium. Though N2O concentration was kept at 50% to prevent intraoperative hypoxemia, the necessary enflurane concentration was low (almost 1% or lower). Serum NH3 level during operation was stable (100-110 micrograms.dl 1), and the level decreased (66-90 micrograms.dl-1) postoperatively. Postoperatively, this patient's consciousness level fluctuated with or without flapping tremor. The treatment of hepatic encephalopathy with lactulose, aminoleban EN and maalox were effective. Problems of perioperative and anesthetic management of a patient for upper abdominal surgery with severe liver dysfunction associated with hyperammonemia were discussed. PMID- 2232131 TI - [Intraoperative anoxic spells in patients with tetralogy of Fallot]. AB - We experienced 5 cases of intraoperative anoxic spell in 48 patients with tetralogy of Fallot (TOF). One of 5 cases had tetralogy with pulmonary atresia (Type A), and the others had tetralogy alone (Type D). The patient of type A who had anoxic spells during preoperative period had been on chronic propranolol therapy. However, the patients of type D had no anoxic spells during preoperative period and one in this type had not been on beta-adrenergic blocking drugs preoperatively. One patient was anesthetized with fentanyl-diazepam-O2, and the others were anesthetized with morphine-diazepam-O2. We used mainly alpha adrenergic drugs and sodium bicarbonate for the therapy of intraoperative anoxic spells. Concerning the intraoperative anoxic spell, we have to be aware in the management of the patients with TOF, whether the patient had anoxic spells during preoperative period or not. PMID- 2232132 TI - [Anesthetic experience of a patient with blue rubber bleb nevus syndrome]. AB - We report an anesthetic experience of a 63-year-old female patient with blue rubber bleb nevus syndrome who underwent an open reduction of the fracture of the right femur. The syndrome is characterized by bluish nevus scattered throughout the skin of the whole body and angiomas of the gastrointestional tract causing serious bleeding. Anesthesia was induced with thiopental followed by intravenous injection of succinylcholine chloride and maintained with neuroleptanesthesia in nitorous oxide and oxygen. The course of anesthesia and emergence from anesthesia were uneventful. Anesthetic management of patients with blue rubber bleb nevus syndrome was also discussed. PMID- 2232133 TI - [Anaphylactic shock following topical use of thrombin for irrigation of urinary bladder]. AB - A 55-yr-old male with carcinoma of bladder received transurethral coagulation (TUC) under epidural anesthesia. A few min after the operation, he went into anaphylactic shock during irrigation of urinary bladder with thrombin solution. The symptoms were epigastralgia, circulatory collapse, skin rashes over the whole body and dyspnea. Oxygen inhalation and iv administration of epinephrine and steroid were performed, and his general condition improved within several hours. On the 2nd day after recovery from the anaphylactic shock, the patient received prick test on several agents which he had been given during operation. Prick test and RAST (radioallergosorbent test) on thrombin were positive. Based on our experience, thrombin may act to produce anaphylactic reaction. Although anaphylactic shock following topical thrombin is rare, we feel that thrombin should not be used without prick test. PMID- 2232134 TI - [Massive water infusion into the patient's trachea during the use of cascade type heated humidifier]. AB - A case of an inadvertent massive infusion of water via the humidifier module into the trachea during the use of cascade type heated humidifier is described. A Fisher and Paykel anesthetic humidifier was employed in the exhalation side of Jackson Rees type breathing circuit between the anesthesia machine and patient's endotracheal tube. During anesthesia for inguinal hernia, fresh gas flow was 6 liters per minute in the breathing circuit. Humidifier module was inadvertently upside down, and the water in the module was abruptly injected into the patient's trachea and we could not ventilate for a short period of time. This water infusion into the trachea was caused by a large supply of fresh gas flow into the breathing circuit and by narrowing of tube diameter. It is essential, when using heated humidifier, to examine it carefully before anesthesia. PMID- 2232135 TI - [A cone shaped one-way valve for an extracorporeal bypass circuit]. AB - For an extracorporeal circulation, either a unidirectional pump or a one-way valve is required. Most of the one-way valves developed so far for a cardiac valve operation have excellent rheological features. But, they are too expensive to be thrown away after a short usage in a disposable bypass circuit. Though a ball valve is simple to make and not expensive, the spherical float inside the valve causes a turbulence in the down stream. This turbulence in the blood stream will become a cause of hematological side effects during the extracorporeal circulation. To prevent this turbulence, we designed a cone shape float with a hemispherical head and a tapered tail. The valve chamber was also changed to a similar shape with a diameter 4 mm larger than that of the float. Three small notch-like spacers were made near the head of the float to prevent wedging of the float into the cone shape region of the valve chamber. Water passed through the valve with a laminar flow without much resistance. Regurgitation at the valve by reversing pressure was insignificant. But, the valve sometimes fell into dysfunction suddenly. Observation with a videocamera revealed that the float often began a long axis rotation and tail swung in the flow. Then the valve suddenly fell in to dysfunction due to the oblique fixation of the float in the valve chamber. A gentle knock of the valve could resume the valve function. However, the cone shaped valve will not be suitable for an extracorporeal life support system where any hazard must be avoided. PMID- 2232136 TI - [Clinical and laboratory research in anesthesiology]. PMID- 2232137 TI - [A study on the psychological status of perioperative patients]. AB - To evaluate the causes of psychic disturbances after operation, three different psychological tests, Spielberger's rating scale "The State-Trait Anxiety Inventory (STAI)", Maudsley Personality Inventory (MPI) and Baum test, were performed during perioperative periods in 25 patients who received simple total hysterectomy. The score of the A-Trait analyzed from STAI that is trait anxiety, did not change significantly, while the score of the A-State analyzed from that, that is state anxiety, decreased significantly in postoperative period. Especially, the score of the A-State showed gradual decreasing tendency during perioperative period in the patients, who were classified as N+ group in MPI, showing the tendency of nervousness. On the contrary, in the patients of N- group, showing no tendency of nervousness, the score of the A-State increased significantly immediately before operation. In Baum test, most of the patients showed some psychological disturbances even during the postoperative period. From the Baum test, it was shown that they had psychologic fragility and lability even postoperatively, in spite of stabilization of general status. PMID- 2232138 TI - [Effect of epidural anesthesia on the function of hormonal regulation in the hypothalamic-pituitary-testicular axis]. AB - To evaluate the effects of epidural anesthesia on the hypothalamic-pituitary testicular axis, we examined the concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T). The effects of epidural anesthesia on plasma levels of LH, FSH and T were investigated in 8 men aged from 64 to 87 years, suffering from untreated prostate cancer. There were no significant differences in plasma levels of LH, FSH or T between patients under epidural anesthesia and patients under no anesthesia. The effects of epidural anesthesia on plasma levels of LH, FSH and T after LH releasing hormone (LH-RH) administration were studied in 10 men between 65 and 84 years with diagnoses of untreated prostate cancer. Plasma LH and FSH levels increased significantly after LH-RH administration under epidural anesthesia or no anesthesia. Plasma LH and FSH were lower under epidural anesthesia than under no anesthesia. No change in plasma T level was observed after LH-RH administration under epidural anesthesia. We conclude that there is no effect of epidural anesthesia on the hypothalamic pituitary-testicular axis. PMID- 2232139 TI - [Endocrine effects of hypotension induced by nicardipine in rabbits]. AB - Endocrine effects of hypotension induced by nicardipine, a calcium antagonist, were studied in 18 male rabbits under halothane anesthesia. They were randomly divided into two groups; nicardipine (group N; n = 10) and controls (group C; n = 8). No change was noted in plasma catecholamines in group C throughout the experiment, but plasma renin activity decreased progressively. During and after induced hypotension, in group N, plasma epinephrine was significantly higher than the control value. The highest level of plasma epinephrine was seven times of the control value during 30 minutes after induction of hypotension. Plasma norepinephrine of group N was significantly higher than the controls. The maximum increase occurred 60 minutes after induction of hypotension. Plasma renin activity of group N was significantly higher than the control value. Compared with the control value (15.1 +/- 1.8 ng.ml-1.hr-1), plasma renin activity was activated 30 and 60 minutes after induction of hypotension (55.5 +/- 6.0 ng.ml 1.hr-1, P less than 0.001, 50.3 +/- 7.1 ng.ml-1.hr-1, P less than 0.01, respectively). In conclusion, our data show that hypotension by nicardipine activates the renin-angiotensin-sympathetic system. PMID- 2232140 TI - [Free and conjugated catecholamines in gastric and bile juice during surgical operations]. AB - From 40 patients under surgical operation, gastric or bile juice was obtained to determine the possible excretion of free and conjugated catecholamine (CA) into the two kinds of juice. The patients were divided into normal renal function group and chronic renal failure group and former group was further divided into the dopamine (DA)-administered group and the non-DA-administered group. In the non-DA group with normal renal function, the gastric juice contained 0.30 +/- 0.11ng.ml-1 of free and 0.12 +/- 0.06ng.ml-1 of conjugated norepinephrine (NE) and also 0.09 +/- 0.07ng.ml-1 of free and 0.40 +/- 0.10ng.ml-1 of conjugated DA. In DA group, the gastric juice contained 2.01 +/- 0.41ng.ml-1 of free and 3.66 +/ 0.84ng.ml-1 of conjugated DA respectively. Significant differences in DA were observed between two groups. In the bile juice, the conjugated NE increased significantly from 0.15 +/- 0.05 ng.ml-1 to 1.24 +/- 0.34ng.ml-1 and also the conjugated DA increased significantly from 2.17 +/- 0.77ng.ml-1 to 21.33 +/- 5.23ng.ml-1 by infusion of DA at the rate of 2 micrograms.kg-1.min-1 for 197 +/- 48min. In chronic renal failure group, the conjugated NE and DA increased significantly to 1.04 +/- 0.27ng.ml-1 and 1.64 +/- 0.61ng.ml-1 respectively compared to that of normal renal group. It was confirmed that gastric juice and bile juice contain the free and conjugated CA during surgical operation and by the infusion of DA, free and conjugated DA are excreted into gastric juice and bile juice and also conjugated CA in the gastric juice from chronic renal failure group is increased. PMID- 2232141 TI - [Effects of ketamine on somatosensory evoked potentials during nitrous oxide anesthesia in humans]. AB - The effects of ketamine with 60% nitrous oxide were studied on subcortical sensory evoked potentials recorded at Erb's point (N9), neck (N13) and on cortical potentials recorded at the scalp (N20) following median nerve stimulations in 7 neurologically normal patients. Latencies and amplitudes of the potentials were measured and compared with postinduction control values taken during inhalation of 60% nitrous oxide. Ketamine 2 mg.kg-1 (iv) was administered initially and incremental dose was 50 micrograms.kg-1.min-1. N20 latency decreased at 15, 30 minutes after ketamine administration from a control value of 18.7 +/- 0.9 msec to 18.2 +/- 1.1, 18.2 +/- 1.1 msec respectively, and N13-N20 interpeak latency decreased from 6.0 +/- 0.4 msec to 5.5 +/- 0.7, 5.4 +/- 0.7 msec (mean +/- SD). The author concluded that during nitrous oxide-based anesthesia, ketamine did not inhibit specific thalamoneocortical pathways. PMID- 2232142 TI - [Effects of ketamine on voltage-dependent Ca2+ current in single smooth muscle cells from rabbit portal vein]. AB - The effects of ketamine on membrane potentials and voltage-dependent Ca2+ current were studied in dispersed single smooth muscle cells from rabbit portal vein. The resting membrane potential (-56.2 +/- 1.5mV) was not affected by ketamine (10(-5) 10(-3)M). The duration and the amplitude of the action potential evoked by intracellular stimulation were significantly decreased by ketamine in the concentrations of 10(-4)M and 10(-3)M. Voltage-gated Ca2+ current in single smooth muscle cells was apparently decreased by ketamine at concentrations of between 10(-5)M to 10(-3)M. The activation threshold of Ca2+ current (approx. 30mV) was also decreased by ketamine. Therefore, these results suggest that inhibition of the contractile response by ketamine in vascular smooth muscle from rabbit portal vein may be attributable to the inhibition of the Ca2+ current. PMID- 2232143 TI - [Antibacterial activity of local anesthetics]. AB - In order to study the antibacterial activity of local anesthetics quantitatively, we procured their minimum inhibitory concentration (MIC), killing curves and postantibiotic effect (PAE), using the standard colony of Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 14990 and Pseudomonas aeruginosa NCTC 10490. Both bupivacaine and lidocaine had bactericidal activity at a clinical concentration. MIC of the former was lower than that of the latter, and it means that bupivacaine has a greater antibacterial activity than lidocaine. At the same concentration, the commercial solutions, such as Xylocaine and Marcain, which contain preservatives, showed a greater antibacterial activity than the pure anesthetic solutions which contain no preservatives. However, the preservatives had no bactericidal activity, but weak bacteriostatic activity. PMID- 2232144 TI - MRSA meningitis in postoperative patients. Report of 4 cases. AB - Four cases of postoperative meningitis caused by methicillin-resistant Staphylococcus aureus (MRSA) are reported together with a review of the literature. These 4 cases were treated successfully by intravenous administration of minomycin, fosfomycin, and cefmetazole. Factors associated with the development of meningitis included multiple craniotomies, the presence of ventricular drainage or a ventriculo-peritoneal shunt, and irradiation. PMID- 2232145 TI - [Clinical experience with chemotherapy using sulbactam/cefoperazone for severe infections accompanying malignant hematological disorders]. AB - Clinical and bacteriological efficacies of sulbactam/cefoperazone (SBT/CPZ) were studied in 44 patients with serious infections associated with hematological malignancy. 1. SBT/CPZ was clinically effective in 33 cases (76.7%). Excellent effects were obtained in 23 cases, good effects in 10 cases and fairly good effects in 7 cases. Clinical effectiveness of SBT/CPZ was not dependent on neutrophil number in peripheral blood. 2. Bacteriologically SBT/CPZ was effective against all of the isolated organisms from 21 cases. 3. Adverse reactions were not significant except one case with eruption, 2 cases with abnormalities in hepatic function tests and 3 cases with abnormalities in renal function tests. PMID- 2232146 TI - [Studies on acetylspiramycin. 1. Separation and chemical structures of acetylspiramycin components]. AB - 1. A macrolide antibiotic acetylspiramycin (ASPM) was separated into seven fractions using high performance liquid chromatography (HPLC) with Lichrosorb RP 8 and mobile phase of a mixed solvent of 0.025M phosphate ammonium (pH 7.4) and acetonitrile at a ratio of 10:18. 2. Five components were purified over 90%, and analyzed using mass spectroscopy, 1H NMR, and 13C NMR, and their chemical structures were determined as 4''-acetylspiramycin I, 4''-acetylspiramycin II, 4''-acetylspiramycin III, 3'',4''-diacetylspiramycin II and 3'',4'' diacetylspiramycin III, respectively. 3. The weight component ratio of the seven fractions of ASPM separated by HPLC was constant throughout several lots of ASPM which had been stocked for nearly 15 years at room temperature, indicating an excellent chemical stability of the antibiotic. 4. Some physicochemical parameters were determined for the five ASPM components. Solubilities in water at 24 degrees C were in a range from 0.14 mg/ml to 4.9 mg/ml, and they were, in the decreasing order, 3'',4''-diacetylspiramycin III, 3'',4''-diacetylspiramycin I 4''-acetylspiramycin III, 4''-acetylspiramycin II, and 4''-acetylspiramycin I. Relationships between solubilities and numbers and positions of acyl substituents in spiramycin molecule are discussed. PMID- 2232147 TI - [A clinical study on ceftazidime in the treatment of intractable respiratory infections]. AB - Ceftazidime (CAZ) was administered to 51 patients (37 males, 14 females) with respiratory infections including severe cases, accompanied by various underlying respiratory diseases. The clinical efficacy and side effects of CAZ were investigated. The mean age and body weight of these 51 cases were 62.6 years and 48.0 kg, respectively. CAZ was administered by intravenous drip infusion (daily dose of 2-4 g) for a mean of 14.7 days to a mean total dose of 56.7 g. Clinical efficacy rates were 64% (18 of 28 cases), 80% (16 of 20 cases) and 67% (2 of 3 cases) for airway and intermediary regional infections, pneumonia (including lung abscess) and pyothorax, respectively. In the bacteriological study, efficacy rates and bacterial eradication rates were 69% and 67%, 33% and 20%, 100% and 100%, and 100% and 100% for infections caused by Pseudomonas aeruginosa (13 cases), Staphylococcus aureus (6 cases), Streptococcus pneumoniae (6 cases) and Klebsiella pneumoniae (4 cases), respectively, and bacterial eradication was achieved in both of 2 cases of Peptostreptococcus anaerobius and 2 cases of Haemophilus influenzae, and 1 case each of Peptococcus sp., Fusobacterium necrophorum and Serratia marcescens. Side effects observed were eruption in 1 case (2%) and elevated GOT, GPT and Al-P values in 1 case (2%), but these cases tended to recover after CAZ treatment was discontinued. PMID- 2232148 TI - [Cerebrospinal fluid transfer of cefbuperazone in the blood-brain barrier lesions of neurosurgical patients]. AB - Cefbuperazone (CBPZ) was given in 15 patients after surgery. There was no infections except for 1 case in which signs of infections were suspected. As side effects, slight elevations in hepatic transaminase levels were observed in 3 patients during the CBPZ chemotherapy. CBPZ concentrations in 7 patients were studied. The subjects were divided into 3 groups according to CT finding during the chemotherapy to correlate CBPZ concentrations to degrees of blood-brain barrier lesions; Group I: no enhancement, Group II: mild or focal enhancement, Group III: diffuse and marked enhancement. It was interesting to note that the more marked enhancement were obtained, the higher levels of CSF concentration of CBPZ. PMID- 2232150 TI - [Influence of cefodizime via intravenous bolus injection on human fecal flora]. AB - Cefodizime (CDZM), a newly developed injectable cephem antibiotic, was given to 8 healthy male volunteers with ages 23-28 years (mean: 24 years) and body weights 54-73 kg (mean: 64 kg). 4 volunteers received 2 g b.i.d., intravenous infusion for 5 days, and 4 volunteers had 4 g b.i.d. for the same duration. We studied changes in bacterial flora and drug levels in feces, as well as changes in susceptibility of isolated microbes to CDZM, cefmetazole, cefotaxime (CTX) and cefoperazone. Adverse drug reactions and changes in laboratory findings were also investigated. The following results were obtained. 1. In fecal flora for the 2 g b.i.d. group, on day 3 of treatment Enterobacteriaceae were identified in only 2 of the 4 cases. Individual microbe counts decreased or fell below detection limit (10(2) cells/g) on day 3 of treatment. Colony forming units (CFUs) of Enterobacteriaceae on day 5 of treatment were similar to those on day 3. After the end of treatment, its CFUs increased. The mean CFU of Enterobacteriaceae on day 10 after the end of treatment increased to about the same level as before dosing. However, some microbes did not revert to pretreatment levels. Of other Gram-negative bacilli, Pseudomonas sp. increased in one case transiently on day 3 of treatment. After day 3 of treatment, its CFU decreased. Gram-positive microbes showed various changes. Mean CFU of yeast like organism (YLO) increased between day 3 of treatment and day 3 after the end of treatment and its mean CFU decreased on day 10 after the treatment. As for anaerobes, CFUs of Bacteroides fragilis group organisms and overall anaerobes showed no distinctive changes. Clostridium difficile were detected in two cases. In one case, C. difficile was noted at levels between 1.1 X 10(3) cells/g and 2.0 X 10(6) cells/g at the following sampling times: days 1 and 3 of treatment and days 3, 5, 10 and 20 after the end of treatment. In other case, it was noted at levels of 1.8 X 10(5) cells/g on day 20 after the end of treatment. D-1 toxin was detected in one case before dosing, and in three cases (the concentration of D-1 toxin was 250 ng/g or 500 ng/g) on day after treatment. Enterobacteriaceae in fecal flora of 4 cases given 4 g b.i.d. frequently decreased or fell below detection limit on days 3 and 5 of treatment and day 3 after the end of treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2232149 TI - [Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1987). II. Background of patients]. AB - In the retrospective survey of the sensitivity of clinical isolates reported in this journal, patients' backgrounds were also investigated. Some findings are summarized below. 1. Age distribution by sex: Patients with ages 50 years and older accounted for a majority, irrespective of their sexes amounting 67.6% for both sexes combined. 2. Annual distribution of sexes by age group: Females accounted for a majority in younger age brackets, but the proportion of males increased with age, accounting for a majority in patients 70 years or older. This pattern has been repeated practically every year. 3. Distribution of infection types by sex: Complicated urinary tract infections were predominant in males, while simple urinary tract infections were more frequent in females. 4. Annual distribution of sexes by type of infection: Complicated and simple urinary tract infections combined accounted for approximately 70% in both males and females. This pattern has been repeated practically every year. 5. Distribution of infection types by age: Patients of advanced ages were predominant as a whole but this trend was particularly pronounced in complicated urinary tract infection cases. 6. Annual distribution of infection types by age: The frequency of simple urinary tract infections among patients older than 20 years of age declined with age and this pattern has been repeated practically every year. Among patients older than 20 years of age, annual frequencies of complicated urinary tract infections have been on the decrease. 7. Distribution of isolated bacteria by sex: Escherichia coli was more frequent in females, while Enterococcus faecalis and Pseudomonas aeruginosa were more frequent in males. Compared with the previous year, the frequencies of coagulase-negative staphylococci, Enterococcus spp., and E. coli increased, while that of P. aeruginosa decreased. 8. Distribution of isolated bacteria by age: E. coli was most frequent on the whole, followed by E. faecalis, P. aeruginosa, Klebsiella spp., and coagulase-negative staphylococci, in that order. By age group, E. coli was frequent in younger patients and the frequencies of E. faecalis and P. aeruginosa increased with age. 9. Annual distribution of isolated bacteria by infection type: Coagulase-negative staphylococci increased as a whole and P. aeruginosa and Serratia marcescens decreased compared to 1986, but E. coli continued to be the most frequent. E. coli was isolated from a majority of simple urinary tract infection cases. The frequencies of E. faecalis and P. aeruginosa were high in cases of complicated urinary tract infections.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2232151 TI - [Synergy between sulbactam and ampicillin or cefoperazone in antimicrobial activity against beta-lactamase producing microorganisms. Results with the use of microdilution broth method]. AB - Antimicrobial activities of sulbactam (SBT) with ampicillin (ABPC) or with cefoperazone (CPZ), in other words, the effects of SBT, an beta-lactamase inhibitor, against beta-lactamase producing strains of clinical isolates, were studied using microdilution broth method. 1. beta-Lactamase producing strains such as Staphylococcus aureus, Branhamella catarrhalis, Haemophilus influenzae, Escherichia coli and Klebsiella pneumoniae decompose benzylpenicillin (PCG) which is one of substrates of the acid-metry disc method and show a strong reaction, while they do not decompose cefazolin (CEZ), another substrate, showing no or weak reaction. Thus, it is suspected that beta-lactamases produced by these organisms are mainly penicillinase (PCase). MIC-distributions of ABPC and CPZ against these clinical isolates which seemed to produce PCase shifted to lower MIC ranges with MIC's reduced to 1/4 or below when 0.025 to 0.39 microgram/ml of SBT was added. 2. It appears that beta-lactamase produced by Proteus vulgaris may be oxyiminocephalosporinase (CXase), because P. vulgaris showed strong reaction on CEZ, but moderate reaction on PCG in the acid-metry disc method. MIC distribution of ABPC and CPZ against P. vulgaris shifted to a lower range with MIC's of 1/4 or below when 0.20 to 0.39 microgram/ml of SBT was added. 3. All the test strains of Pseudomonas aeruginosa showed strong reaction on CEZ but only 56% of the test strains showed reaction on PCG. It appears that the beta-lactamases which showed strong reaction on CEZ is cephalosporinase and is encoded in chromosome, while those beta-lactamase that showed strong reaction on PCG is encoded in a plasmid which was acquired secondarily by P. aeruginosa. MIC distribution of CPZ against P. aeruginosa shifted to a lower range with MIC values of 1/2 or below with the addition of SBT at 1.56 micrograms/ml. 4. It appears that the synergy of SBT with ABPC or with CPZ against the PCase or CXase producing strains may occur in the presence of SBT at a concentration far less than that reported previously. PMID- 2232152 TI - [Influences of postoperative prophylaxis treatments on vaginal bacteria flora at hysterectomy]. AB - We performed abdominal hysterectomy and administered aztreonam (AZT) for prophylaxis of postoperative infections, and investigated influences of the antibiotics on vaginal bacterial flora. The obtained results are summarized as follows. 1. Patients administered with AZT were studied (n = 48) for bacteria isolated from their vaginae preoperatively and at the 7th and the 14th days postoperatively. Groups of patients administered with cephalothin (CET), cefamandole (CMD) and latamoxef (LMOX) were also studied for comparison. 2. In the AZT group, the rate of isolation of aerobic Gram-positive bacteria was high (68.8-81.4%) whereas those of aerobic Gram-negative and anaerobic bacteria were low. 3. When changes in isolation frequencies of bacteria from the subjects preoperatively to postoperatively were compared, the following tendencies were observed: increase in the rate of aerobic Gram-positive bacteria was larger in the LMOX group than in the AZT group whereas decrease in the rate of aerobic Gram negative bacteria was largest in the LMOX group followed by the AZT group then by the CMD group. Rates of decrease of anaerobic bacteria showed similar tendencies to the latter. Isolation rates of Candida sp. showed the largest increase in the LMOX group, followed by CET, CMD then AZT groups. PMID- 2232153 TI - [Cardiotoxicity study of ME2303 with the interval intravenous injections to rats]. AB - Cardiotoxic effects of ME2303 were studied upon interval intravenous administrations to rats in comparison with those of doxorubicin (ADR). ME2303 at two dose levels of 3 and 9 mg/kg/day or ADR at a dose levels of 3 mg/kg/day was injected once a week for 3 weeks to female Sprague-Dawley rats (SPF) of 5-weeks of age. ADR depressed body weight gain, decreased food intake and increased water intake. Microscopic observation on the myocardial tissues revealed that ADR caused necrosis and cell infiltration, edema and disarrangement of myofibrils in some of ADR-treated rats. On the other hand, ME2303 showed no significant effects except that some decrease of food intake was observed at a dose level 9 mg/kg/day. No changes in left ventricular functions were observed in perfused hearts isolated from ADR- or ME2303-treated rats. However, about 133 ng/g of ADR remained in the hearts even at 1 week after the final administration whereas ME2303 or its metabolites were not detected, suggesting that ADR may cause disturbance of ventricular function and more cardiomyopathy after a longer term than 1 week following the final administration. These results suggest that the cardiotoxicity of ME2303 is weaker than that of ADR in rats. PMID- 2232154 TI - [Single dose oral toxicity study of BMY-28100 in juvenile rats and dogs]. AB - In order to investigate the single dose oral toxicity of BMY-28100 in juvenile animals, the drug was administered in single doses to 4-day-old and 14-day-old Crj: CD (SD) rats of both sexes at a dose of 2,000 mg/kg, and to 4-week-old beagle dogs of both sexes at doses of 500, 1,000 and 2,000 mg/kg by oral route. The results obtained are summarized as follows: 1. In rats, decreases of the body weight gain were observed for male and female rats treated with the drug on postnatal day 4 through 5 days and 3 days after dosing, respectively. There were no apparent drug-related toxic signs. No deaths occurred during the observation period. Enlargement of the cecum was found in a few rats of both sexes administered the drug on postnatal day 4 or 14. 2. In dogs, watery-mucous diarrhea observed at 2 to 3 hours after dosing in all dose groups was not dose related. This finding lasted in some dogs till 4 days after dosing. An increased incidence of emesis was induced in all males at 2,000 mg/kg and all females of all dose groups except one female at 2,000 mg/kg. Body weights increased normally for all dogs, but one male at 1,000 mg/kg showed a transient decrease in food consumption. No drug-related histopathological changes were found. Based upon these results, BMY-28100 at 2,000 mg/kg induced no apparent toxic changes in the present experimental conditions. Therefore, the single dose oral toxicity of the drug in juvenile animals appeared to be very slight and generally similar to that in adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232155 TI - [Four-week repeated dose oral toxicity study of BMY-28100 in juvenile rats]. AB - In order to investigate the repeated dose oral toxicity of BMY-28100 in juvenile rats, the drug was administered orally to 4-day-old Crj: CD(SD) rats of both sexes at daily doses of 250, 750 and 1,500 mg/kg for 4 weeks. The results obtained are summarized as follows: 1. Soiling around the anus apparently correlated to soft stool or diarrhea was observed at 750 and 1,500 mg/kg and the incidence appeared to be dose-related. Three deaths including 1 death due to cannibalization occurred at 750 and 1,500 mg/kg, but they were considered to have been caused by misadministration. 2. Slightly depressed body weight gains were noted in the 750 and 1,500 mg/kg dose groups during early dosing period. 3. Slightly increased averages of food and water consumption observed predominantly in the 1,500 mg/kg dose group at later dosing period and the recovery period were considered as incidental and unrelated to the treatment. 4. Though average values of some blood chemical parameters were slightly suppressed or elevated compared with those of controls at the completion of the dosing and recovery periods, these differences appeared to be generally within normal ranges and to be irrelevant to the drug treatment. No definitive drug-related changes were detected in hematological examinations and urinalyses. 5. The average absolute and/or relative organ weights of the brain, thymus, lungs and liver from male rats in the 1,500 mg/kg dose group were lower than those of the corresponding organs from controls. However, these findings were not considered to be toxicologically significant because no corroborative changes were detected microscopically. 6. Macroscopic and microscopic examinations demonstrated dilatation of the cecum in a dose-related fashion. This phenomenon has been reported with other antibiotics and appears to be drug-related and reversible caused by an alteration of the gut flora. There were no other microscopic changes that were considered to be related to the administration of the drug. 7. Electron microscopic examination revealed no drug-related changes in the liver and kidneys from rats of the 1,500 mg/kg dose group. Based upon these results, the no-effect dose level of BMY-28100 was estimated to be 250 mg/kg/day for both male and female juvenile rats in the 4-week repeated dose oral toxicity study if the finding of cecum dilatation was not considered.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2232156 TI - [Four-week repeated dose oral toxicity study of BMY-28100 in juvenile beagle dogs]. AB - Three groups, each consisting of 3 male and 3 female juvenile beagle dogs, were orally given BMY-28100 for 4 weeks at dose levels of 50, 160 and 500 mg/kg/day, respectively. Additionally, one male and one female dogs were added to each of the control and high dose groups in order to examine the recovery, and observed for 4 weeks after withdrawal of BMY-28100. The results obtained are summarized as follows: 1. BMY-28100 provoked an increased incidence of emesis in the 500 mg/kg group during the treatment period. 2. BMY-28100 sporadically brought distention of the cecum containing considerable amounts of contents in dogs sacrificed after the 4-week administration period. However, no macroscopic or microscopic changes were observed in the cecum itself after removal of the contents. In the 500 mg/kg group, hypocellularity in the sternum bone marrow was observed in a male and a female, and thymic atrophy in a male. 3. No changes ascribed to BMY-28100 treatment were detected after the 4-week recovery period. Based upon these results, the no-effect dose level of BMY-28100 was estimated to be 160 mg/kg/day, except for effects on the cecum. PMID- 2232157 TI - [Immunological properties of BMY-28100 and cefepime]. AB - Immunogenicity, eliciting antigenicity and cross-reactivity of new cephem antibiotics, BMY-28100 and cefepime, were studied by means of passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and active systemic anaphylaxis in guinea pigs, and of PCA in mice and the results were compared with those obtained with reference antibiotics. In addition, the direct Coombs' reaction of the human blood was examined in vitro for the test antibiotics as compared with reference antibiotics. The results obtained are summarized as follows: 1. Immunogenicity Immunogenicity of unconjugated antibiotics was examined using the corresponding conjugates with bovine gamma-globulin (BGG) as eliciting antigen. When used as emulsions with Freund's complete adjuvant, cephalothin (CET) and benzylpenicillin (PCG) produced IgG1 and IgM antibodies in guinea pigs. However, cefepime as well as cephalexin (CEX) did not produce these antibodies, and BMY 28100 showed slightly active sensitization only for anaphylactic shock. In BALB/c and C3H/He mice, BMY-28100 and cefepime failed to produce antibodies under the experimental condition while IgE antibody formation to CET was observed. 2. Eliciting antigenicity Unconjugated CET and PCG provoked anaphylactic signs in guinea pigs sensitized with their conjugates with rabbit serum albumin (RSA). Cefepime, however, provoked no anaphylactic shock and BMY-28100 as well as CEX showed slight signs. In the other systems examined, no reactions were observed when elicited with BMY-28100, cefepime or the reference antibiotics. 3. Immunological cross-reactivity BMY-28100 did not cross-react with the reference antibiotics. While the antiserum to the RSA conjugate of CET provoked weak cross reaction on PHA with the BGG conjugate of cefepime, the antiserum to the RSA conjugate of cefepime failed to react with the BGG conjugate of CET. Other cross reactivities of cefepime were not observed against the reference antibiotics. 4. In vitro direct Coombs' reaction BMY-28100 did not induce the Coombs' reaction of the human blood in vitro at the testable concentration of 10 mg/ml. Cefepime or cefazolin (CEZ) caused no reaction even at a high concentration of 80 mg/ml, while CET and PCG caused a positive reaction at 10-40 mg/ml and 60 mg/ml, respectively. As shown above, immunogenicity and eliciting antigenicity of BMY 28100 and cefepime were somewhat weaker than CET and PCG but similar to CEX, and cross-reactivities of the test antibiotics with these reference antibiotics were not observed in general. The ability of BMY-28100 to give a positive reaction in the Coombs' test was weaker than that of CET, and that of cefepime was weaker than CET and PCG and equivalent to CEZ.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2232158 TI - [General pharmacology of BMY-28100]. AB - General pharmacological properties of BMY-28100, a new semisynthetic oral cephalosporin, were studied in experimental animals. The obtained results are summarized as follows: 1. BMY-28100 had no effect on gross behavior and the central nervous system in mice and rats nor on EEG activities in rabbits. 2. BMY 28100 did not affect the smooth muscle isolated from rats, guinea pigs or rabbits nor did it influence ganglionic transmission in cats. 3. Effects of BMY-28100 on the atrium and heart isolated from guinea pigs were not obvious. Several parameters of the cardiovascular system were examined and found unchanged by administration of BMY-28100 to rabbits. 4. In the digestive system, BMY-28100 had no effect on charcoal meal transport in the small intestine of mice. In rats, however, gastric secretion was reduced at a dose level of 125 mg/kg or higher and bile secretion was enhanced at a dose level of 500 mg/kg. 5. BMY-28100 had no effect on neuromuscular transmission in rabbits and showed no local anesthetic activity in guinea pigs. 6. BMY-28100 decreased urine volume and urinary excretion of electrolytes in dose-dependent manners in rats. Sulfobromophthalein excretion in rats was inhibited only at the highest dose tested. BMY-28100 had no effect on blood coagulation and red blood cell resistance in rats or rabbits. BMY 28100 revealed no antiinflammatory activity in rats. 7. BMY-28167, a trans-isomer of BMY-28100, had no or weak effects on some of above test systems when compared with BMY-28100. These results suggest that BMY-28100 has hardly any pharmacological properties leading to severe adverse reactions in clinical use. PMID- 2232159 TI - [Studies on the pharmacokinetics of BMY-28100 (I)]. AB - The pharmacokinetics of BMY-28100 have been studied in rats and monkeys upon oral administration of 14C-BMY-28100. 1. In rats administered with BMY-28100 at a single oral dose of 20 mg/kg, the peak blood level of the drug was 6.30 micrograms equiv./ml at 1 hour after administration. Blood levels declined biphasically, thereafter. The AUC value was 37.0 micrograms equiv..hr/ml, and was 97% of that observed after intravenous administration. This suggests that BMY 28100 is absorbed at a high absorption rate from the gastro-intestinal tract. 2. In monkeys administered with a single oral dose of 20 mg/kg, the peak blood level was 4.26 micrograms equiv./ml at 3 hours after administration. Thereafter, blood levels declined biphasically as did in rats. The AUC was 38.9 micrograms equiv..hr/ml, which is similar to that observed in rats. 3. Urinary and fecal excretion after 20 mg/kg oral administration were 60.9% and 38.1%, respectively, in rats, and 40.3% and 51.2%, respectively, in monkeys. 4. Although absorption from gastro-intestinal tract was delayed by food intake, this did not affect the total amount absorbed in rats. 5. The absorption rates were similar in rats administered with 20 and 60 mg/kg, while a lower rate was obtained with 200 mg/kg. 6. In rats, biliary excretion was 28.5% of dose administered. Thirty-nine percent of the biliary radioactivity was reabsorbed from the intestinal tract. 7. No differences between sexes were observed in absorption and excretion in rats administered with the drug at 20 mg/kg orally. 8. In rats administered with 20 mg/kg, the radioactivity distributed rapidly to the whole body. High levels of radioactivity were found in gastro-intestinal tract, kidney, urinary bladder, aorta and liver. The radioactivity was removed rapidly from the tissues. Autoradiograms of the whole body were consistent with the measured tissue distribution. Relatively high levels of radioactivity were found in aorta, fascia, and ligament at 0.5, 1, 6, and 24 hours. 9. In vivo protein binding, which increased with time after administration, was 56.8 to 73.5% in rat and 36.3 to 58.6% in monkey. The in vitro protein binding at 0.4 to 50 micrograms/ml of drug concentration was 50.0 to 54.7% in rat, 32.3 to 35.0% in monkey, and 33.4 to 36.3% in human. 10. A stability test of 14C-BMY-28100 in plasma solution showed that the drug decomposed gradually into relatively polar compound(s). At 8 and 24 hours, the proportions of unchanged 14C-BMY-28100 were 53.2% and 5.9%, respectively. PMID- 2232160 TI - [Studies on the pharmacokinetics of BMY-28100 (II)]. AB - Studies were done in rats on placental transfer and excretion into milk of 14C BMY-28100 upon single oral administration. Studies on absorption, distribution and excretion of 14C-BMY-28100 were also done upon multiple dosing. 1. Fetal tissue concentration of the drug reached a maximum at 6 hours after dosing on day 18 of gestation. The highest concentration observed was only 0.56 microgram equiv./g in fetal kidney; The transfer of radioactivity into the fetus was low. Similar results were obtained from whole body autoradiograms performed in rats on day 12 and day 18 of gestation. 2. Concentrations of radioactivity in milk reached a maximum of 0.60 microgram equiv./ml at 1 hour after administration, and gradually decreased thereafter. The maximum concentration in milk was 10% of the plasma concentration measured at the same time. 3. In the multiple oral administration study, 24 hours blood levels of radioactivity rose progressively with each dose, and reached a level 3.8 times higher than that observed with single dosing by the final (21st) administration. Tissue concentrations were relatively high in aorta, kidney and large intestine as were found upon single administration. However, the ratios of these levels between multiple and single dosing were lower than those observed in blood; 1.7, 3.6 and 2.9 for aorta, kidney and large intestine, respectively. Urinary and fecal excretion were constant after the 2nd administration. PMID- 2232161 TI - [Studies on immunity to Babesia gibsoni in dogs immunostimulation by Bordetella bronchiseptica]. AB - Four species of bacteria, Corynebacterium anaerobium 578, Actinobacillus pleuropneumoniae G-4, Mycobacterium bovis BCG, and Bordetella bronchiseptica A-2, were injected intravenously into mice (5 weeks old, ICR-SPF). The clearance of carbon from the blood stream and the weights of the spleen and liver were determined as indicators of RES stimulation. Mouse footpad reaction was assessed as an indicator of delayed-type hypersensitivity to each species of bacteria. The immuno-stimulative activity of each species of bacteria against bovine serum albumin was monitored by passive hemagglutination assay and the macrophage migration-inhibition test in guinea pigs. Based on the results of the experiments described above, B. bronchiseptica was selected as an immunostimulator (Ims) for immunization trials of the hemo-protozoan parasite, Babesia gibsoni, with inactivated merozoites of B. gibsoni (BgK). Twelve dogs, pointers about 6 months old, were divided into four groups of three dogs each. Group 1 dogs were initially injected with Ims, and later injected with BgK and Ims (BgK+Ims) after a 3-week interval. Group 2 and Group 3 dogs were injected twice, at a 3-week interval, with BgK+Ims and BgK, respectively, and Group 4 served as a control. As the results, the serum antibody titres of Group 1 and 2 were several times higher than that of Group 3, and the cell-mediated immunity to parasites was noticeably stimulated by immunization with BgK+Ims. The peak level of parasitemia following the challenge were over 10% for Group 4 and 4.5% for Group 3, while levels for Group 1 and 2 were 2.5% and less than 1%, respectively. No such major clinical signs of babesiosis as jaundice and anemia were observed in Group 1 or 2. PMID- 2232162 TI - [Relationship between an offensive smell given off from human foot and Staphylococcus epidermidis]. AB - The bacteria isolated from foot skins of 17 volunteers by the swab sampling method were mostly gram-positive cocci, which were identified as Staphylococcus epidermidis by the ID-kit SP-18 (Nissui Co., Ltd). After incubation of S. epidermidis on agar plates containing oleic acid and Tween 80 for 24 h at 35 C, the smell noticed was similar to an offensive smell of human pes. However, under the same conditions, the smell of another staphylococcal species was different from that of S. epidermidis. Except for the staphylococcal species, the colonies isolated from the skins were mostly those of yeast (unidentified) and gave off no offensive smell. From these results, it was considered that the smell of human pes might be given off by S. epidermidis, and if this species is inhibited, the smell would also be inhibited. A selective bactericide for gram-positive bacteria, which is a lotion containing deoxycholic acid, was applied to the feet of the 17 volunteers. The experiments showed that the application obviously decreased the counts of colonies of S. epidermidis and inhibited the smell as compared with controls. PMID- 2232163 TI - Ultrastructural pathological study of left ventricular myocardium in patients with isolated rheumatic mitral stenosis with normal or abnormal left ventricular function. AB - An electron microscopic study of left ventricular myocardium was carried out in 15 patients who had isolated rheumatic mitral stenosis, with particular reference to the relation among ultrastructural pathological findings, the severity of mitral stenosis and left ventricular function. They were divided into 2 groups based on left ventricular performance evaluated by 2-dimensional echocardiography and angiocardiography. The severity of mitral stenosis was determined by hemodynamic data and mitral valve areas measured by 2-dimensional echocardiography. Regardless of the level of left ventricular contractile function we consistently demonstrated varying degrees of ultrastructural pathological alterations of left ventricular muscle cells, involving the myofibrils, mitochondria, nuclei and other elements of the sarcoplasm and membranes surrounding the myocardial cells in all specimens examined. The ultrastructural pathological findings did not correlate with the severity of mitral stenosis reflected in the echocardiographic and hemodynamic data. However, those patients with abnormal left ventricular function always exhibited more extensive loss of myofibrils resulting from either disproportion of the mitochondria-to-myofibril ratio or myofibrillar degeneration. The present investigation provides the morphological data at the ultrastructural level to support the widely held concept of a myocardial factor i.e., the extent of myocardial involvement by the rheumatic process as the basic pathogenetic mechanism responsible for left ventricular dysfunction in patients with isolated rheumatic mitral stenosis. Furthermore, it is suggested that pathological alterations of myocardial ultrastructure were related to the extent of myocardial involvement by the rheumatic process rather than being structural adaptations in response to the hemodynamic derangement. PMID- 2232164 TI - Crossover in baroreflex pathways controlling renal sympathetic nerve activity. AB - Experiments were performed to investigate the physiologic significance of the crossover of baroreceptor afferent input to the contralateral nucleus tractus solitarius (NTS) in terms of reflex control of renal sympathetic nerve activity and to determine the physiologic significance of neuronal crossover which may occur beyond the NTS. Experiments were done in 14 alpha-chloralose anesthetized rabbits. Baroreflex control of left renal nerve activity was determined from responses to phenylephrine-induced increases and nitroglycerin-induced decreases in arterial pressure. Under control conditions, the mean regression slope for changes in renal nerve activity (imp/sec/mmHg change in arterial pressure) was 2.2 +/- 0.5. After unilateral NTS lesion (n = 14) the gain of the reflex was -2.4 +/- 0.4 imp/sec/mmHg. Denervation of baroreceptors ipsilateral to the NTS lesion (n = 6) did not alter the regression slope (-2.7 +/- 0.5 imp/sec/mmHg), but interruption of the contralateral carotid and aortic baroreceptor afferent fibers (n = 8) markedly reduced the slope of the linear regression relationship from 2.4 +/- 0.3 to -1.1 +/- 0.3 imp/sec/mmHg. We interpret these data to suggest that baroreceptor afferent input exerts its major reflex influence via the ipsilateral NTS and that there is modest influence exerted by fibers which cross over to the contralateral side. In addition, since we recorded from the left renal nerves and alternated the side of the NTS lesion, we interpret our findings regarding a lesion in only one NTS to suggest that there is crossover in the baroreflex pathway beyond the NTS which permits the NTS on one side to exert an influence on the renal nerves on the contralateral side similar to that seen when the NTSs on both sides are intact. PMID- 2232166 TI - The spontaneously hypertensive rat. Proceedings of the XXV annual scientific meeting of the Society for the Spontaneously Hypertensive Rat (SHR). September 4 5, 1989, Tokyo. PMID- 2232165 TI - Effects of a calcium-antagonist on vascular sympathetic nerve activity in salt dependent hypertension. AB - The purpose of the present study was to investigate the effects of a Ca2(+) antagonist on vascular sympathetic nerve activity in salt-dependent hypertension. Isolated mesenteric vasculature preparations from reduced renal mass-salt hypertensive and age-matched normotensive control rats were used to examine the effects of diltiazem on vascular responsiveness and norepinephrine release from sympathetic nerve endings. Pressor responses and endogenous norepinephrine release during electrical nerve stimulation were significantly greater in preparations from salt-dependent hypertensive rats than from normotensive control rats. Diltiazem inhibited both stimulation-evoked pressor responses and norepinephrine release in a dose-dependent manner. The attenuation of these responses was more pronounced in preparations from rats with salt-dependent hypertension than in those from control rats. These results indicate that norepinephrine release from vascular adrenergic neurons is enhanced in the mesenteric vasculatures of rats with salt-dependent hypertension. The marked reduction of stimulation-evoked pressor responses and norepinephrine release by diltiazem suggests that enhanced Ca2(+)-dependent adrenergic transmission may contribute to the exaggerated vascular sympathetic tone in salt-dependent hypertension. PMID- 2232167 TI - [Orofacial lymphomas in seropositive patients manifesting the type I human lymphotropic virus (HTLV-I)]. AB - Eleven cases of extranodal orofacial lymphomas (EOFL), consisting of 4 HTLV related and 7 HTLV unrelated EOFLs, have been investigated with regard to their immunohistological and clinical features. The HTLV related EOFLs were found to be of the T-cell phenotype and were associated with a poorer prognosis than the HTLV unrelated EOFLs, most of which were of B-cell origin. The comparatively high incidence of T-cell type in our series was considered to be related to the high percentage of HTLV carriers in our district, an area in which adult T-cell leukemia lymphoma has been found to be endemic. PMID- 2232168 TI - [The expression of NCC-ST-439, a tumor marker, in human breast cancer patients]. AB - The expression and serum level of NCC-ST-439, a tumor marker, has been investigated in 20 primary and 28 recurrent breast cancer patients, and the positive rate was found to amount to 21.1% in primary cases and 42.9% in recurrent cases, respectively, thereby indicating a positive correlation between the expression of NCC-ST-439 and the progression of the diseases. The accordance rate between NCC-ST-439 and CEA was 64.6%; in contrast, the rate between NCC-ST 439 and CA 15-3 was 82.1%, suggesting a difference in specificity against tumor between NCC-ST-439 and CEA. The change in the serum level of NCC-ST-439 in recurrent cases clearly correlated with the effectiveness of the therapy. These findings suggest that measurement of the NCC-ST-439 level, especially in combination with the CEA level, may be useful for the early detection and the monitoring of relapses in breast cancer patients. PMID- 2232169 TI - [Radiotherapy of local regional recurrences of a mastectomized breast carcinoma and its results]. AB - Local-regional recurrences of a breast carcinoma after the mastectomy have been studied. A complete response rate of 89% was noted and this rate was found to decrease with an increase in the size of the mass. The most favorable local control rate was noted in carcinomas of the solitary nodular type where as the worst control late was seen in those with a lymph node metastasis. The 5-year survival rate in all cases was found to be 28.0%, and best in the solitary nodular type carcinomas and worst in carcinomas of the invasive type. Chestwall recurrences associated a local lymph node metastases were found to have a poorer prognosis compared to those without a lymph node metastasis. PMID- 2232170 TI - [The DNA ploidy patterns in early gastric cancers as a criterion for surgery]. AB - A study of the ploidy patterns in gastric cancer has been conducted, focusing on 20 cases diagnosed prior to surgery as early stage gastric cancers. The gastric cancer in 10 cases was confined to the submucosa, where as in the other 10, the gastric cancer had invaded the muscle propria. The DNA ploidy patterns were classified as follows: Type D, Type A1 and Type A2. Even with gastric cancers of less than 2 cm, the likelihood that those with Type A1, and Type A2 patterns would spread into the lymph node was high (A1, 43% and A2, 67%), suggesting that careful consideration should be given to limiting the intended surgery. With gastric cancers of the Type D pattern, however, the incidence of a lymph node metastasis was low. These results are felt to be important factors when considering the extent of surgery. PMID- 2232171 TI - [A clinical and pathological study of small renal cell carcinomas]. AB - Ten cases of a small renal cell carcinoma having a tumor that was 3 cm or less have been studied both clinically and pathologically. In nine of the 10 cases, the tumor had been detected incidentally, and all 9 were asymptomatic. Renal lesion were diagnosed all of the 10 cases by computed tomography and in 9 cases by ultrasonography. The pathological characteristics of small renal cell carcinoma are characterized by an expansive development, an alveolar structure, a clear cell subtype, a low grade nuclear atypism, and a general lack of infiltration. The postoperative follow up period was 20 months on average, and all patients had survived with no appearance of a new lesion. PMID- 2232173 TI - [A case of primary early duodenal cancer]. AB - Reported is a case of a suprapapillary primary early duodenal cancer in a 50 year old male patient who had had a hemicolectomy 15 years earlier for a colon cancer. The patient had undergone upper gastrointestinal endoscopy during a mass screening for abnormalities in the gastro-intestinal tract, and a slightly depressed lesion of the IIa + IIc type, 25 x 20 mm in diameter, was discovered accidentally at the superior duodenal flexure. The subsequent biopsy revealed a well differentiated tubular adenocarcinoma. Thus, the patient underwent a subtotal gastrectomy and a partial duodenectomy with a lymph node dissection. The histology of the resected specimen was the same as that of the biopsy, but only the mucosa was involved. Adenomatous lesions of the colon are known to occasionally accompany upper gastro-intestinal tumor, so that periodic gastro intestinal scrutiny follow-ups are mandatory. PMID- 2232172 TI - [An esophageal cancer with a renal metastasis that was detected and resected as the only focus of recurrence]. AB - Reported is the case of an esophageal cancer presenting a renal metastasis, which was detected and resected as the only recurrent focus. The patient was a 62-year old male. Five months after an esophagectomy, a left renal mass was detected by abdominal computerized tomography, and a rise in the SCC antigen. The urinary cytology suggested a renal metastasis of the esophageal cancer. Thus, chemotherapy and irradiation was performed, followed by a resection. The histology of the resected mass showed a squamous cell carcinoma, similar to the findings at the primary site. A renal metastasis of an esophageal carcinoma usually is latent, but not rarely found on postmortem examination. A nephrectomy for a renal metastasis of an esophageal cancer is rare, and only 8 cases are reported in the literature. PMID- 2232174 TI - [A biliary endocrine cell carcinoma: a report of two cases]. AB - An endocrine cell carcinoma is a carcinoid tumor that has an especially malignant prognosis. We herein report on 2 cases of a biliary endocrine cell carcinoma. Case 1 involved a 68 year old man manifesting a fever, jaundice, hepatomegaly and a ballooned gallbladder. After decreasing the jaundice by PTCD, an exploratory abdominal operation was performed. As a tumor was found at the papilla of Vater, a pancreaticoduodenectomy was done. Case 2 involved a 72 year old woman who was diagnosed as having a gallbladder tumor and cholelithiasis. She was given a cholecystectomy and a choledocholithotomy. These 2 cases had hepatic metastasis within a year and subsequently died. Procedurally, an endocrine cell carcinoma should be treated separately from classical carcinoid tumors. PMID- 2232175 TI - [A case of unresectable pancreatic cancer that responded to UFT chemotherapy]. AB - A 77-year-old patient with an unresectable pancreatic cancer was treated with a combination chemotherapy of UFT (600 mg/day, p.o.) and Lentinan (2 mg/week, i.v.). After three and a half months, a partial response (PR) was achieved, based on the criteria of Koyama, Saito, et al. The findings of the follow up CT scans suggested that 600 mg/day of UFT, rather than 300 mg/day, was effective as a chemotherapeutic agent. Although transient thrombocytopenia (62,000/mm2) and eruption were observed during this therapy, no serious side effects were experienced. After eighteen months of this chemotherapy, the patient has not succumbed and manifests a good quality of life. PMID- 2232176 TI - [Clinicopathological analysis of leiomyosarcomas of the small intestine and a review of the Japanese literature]. AB - An analysis has been made of 9 cases of a leiomyosarcoma of the small intestine that were treated from 1974 through 1989. In two patients (22.2%), a perforation was seen, and a case report of a 59-year-old woman is presented. Further, case reports of leiomyosarcomas in the Japanese literature from 1980 through 1989 were clinico-pathologically analyzed. The frequency of a perforation was found to be 8.6%, and the distribution of the perforated leiomyosarcomas was the same as for the non-perforated cases. The five-year postoperative survival rate was 41.2%. Of note is that 3 out of 10 patients that had survived for 5 years subsequently died of sarcomatosis. PMID- 2232177 TI - [A primary malignant lymphoma of the appendix]. AB - A malignant lymphoma (ML) of the gastrointestinal tract occurs most frequently in the stomach, and ML of the appendix is very rare, with only 16 cases reported in the Japanese literature. Reported is a case of a primary ML the appendix in a 48 year old male, in whom an ileocecal resection was carried out. This case was pathohistologically diagnosed as a diffuse large lymphoma of the B cell type, according to the LSG classification. Therapeutic problems were encountered because of the difficulty in making an early diagnosis. PMID- 2232178 TI - [A renal cell carcinoma mimicking a multilocular renal cyst]. AB - A 38-year old man was admitted to the hospital for an investigation of abnormal ultrasonographic findings of the left kidney. Ultrasonography demonstrated multiple, fluid-filled masses separated by a highly echogenic septa and CT revealed a large cystic mass and a thick, irregular wall in the upper and middle poles. Selective, left renal arteriography showed a hypovascular mass. Thus, a presumptive diagnosis was made of multilocular renal cysts. Taking into accounted the possibility of a renal cell carcinoma. Surgical exploration and a left nephrectomy was performed. Microscopically, a multiloculated renal cell carcinoma thus was diagnosed, A definite, preoperative diagnosis is very difficulty to make in most cases, and surgical exploration is considered to be the only way to achieve an accurate diagnosis. Treatment for a multiloculated cystic renal mass containing multilocular renal cysts is a total or partial nephrectomy. PMID- 2232179 TI - [A carcinosarcoma of the ovary: a case report and a review]. AB - A carcinosarcoma of the ovary, which is a combined epithelial and mesenchymal tumor, is exceeding rare and usually has poor prognosis. Only four known cases, including this case, have been reported in Japan. In our case, after resection a combined chemotherapy consisting of cisplatinum, adriamycin cyclophosphamide and etoposide was administered and the patient had no uneventful postsurgical course. PMID- 2232180 TI - [A pathological study of primary malignant lymphomas of the thyroid]. AB - Thirty cases of a primary malignant lymphoma (ML) have been studied clinicopathologically and immunohistochemically. The average age of the patients was 59.1 years, and the ratio of males to females was 1:1.7. According to the Kiel classification of MLs, 53.3% had a low grade malignancy and 46.7% were a high grade malignancy. Therefore, the number with a low or a high grade malignancy was almost equal. Most of the low grade malignancies were ML, centroblastic centrocytic, and most of the high grade malignancies were ML, lymphoblastic. From histopathological and immunohistochemical studies, most cases were considered to be of B-cell origin and two thirds of the cases were regarded as being of a follicular center cell origin. Prognosis was better than that of other MLs. Finally, MLs of the thyroid were found combined more frequently with chronic thyroiditis of the Hashimoto type than malignant epithelial neoplasms. PMID- 2232181 TI - [A case-control study of risk factors of breast cancer detected by mass screening]. AB - A case-control study has been performed to elucidate the risk factors of women with a breast cancer that was detected by mass screening. Studied were the cases of fifty-two women with a primary breast cancer that had been detected by mass screening from 1978 to 1989. Age-matched mass screening controls and hospital controls were randomly selected at the rate of two controls for each case. Risk factors investigated were the age at menarche, the age at marriage, the number of pregnancies, the number of full-term pregnancies, the age at first delivery, the status of lactation, the age at menopause, the family history of breast cancer, benign breast disease, exogenous hormonal agents, and obesity. In comparing the mass screening subjects with the controls, a significant odds ratio (OR) was shown in no lactation (OR = 2.67, p = 0.02) and the history of a previous benign disease (OR = 2.56, p = 0.03). No lactation (OR = 2.29, p = 0.02) was significant when compared with the hospital controls. Furthermore, early menopause and an early age at first delivery seemed to act as a protective factor against breast cancer. PMID- 2232182 TI - [The relation of stone and carcinoma of the gallbladder based on the mucosal findings]. AB - Based on the mucosal findings in gallbladder patients, intestinal metaplasia was found in 18.4% of such cases without a stone or a carcinoma, in 30% of the with a bilirubin stone, in 37.7% of those with a cholesterin stone, in 69.1% of those with a carcinoma but without a stone and in 78.9% of those with both a carcinoma and a stone. In contrast the incidence of a well differentiated adenocarcinoma was more frequent in the cases with a stone (more often a cholesterin stone than a bilirubin stone) than in cases without a stone. Similarly, the incidence of intestinal metaplasia was more frequent in those with a cholesterin stone than in those with a bilirubin stone. Further, small size lesions were found to be more frequent in the cases of a cancer with a stone. Granular early carcinomas within the superficial muscle layer are usually resected under the diagnosis of gallstone, whereas early carcinoma that protrude are resected as a carcinoma. PMID- 2232183 TI - [A clinical evaluation of the CA 72-4 serum level as a possible tumor marker]. AB - The level of CA 72-4 in serum has been measured in various diseases by an immunoradiometric assay using CA 72-4 RIA Kit for an evaluation of its clinical significance as a possible tumor marker. CA 72-4 showed a high positive rate in patients with ovarian and bile duct cancers. In contrast, the false positive rate was low in benign gynecological and digestive diseases. Serum CA 72-4 was found to be increased in patients with a mucinous cystadenocarcinoma and in other histological types in the early stages of an ovarian cancer. Further, the serum CA 72-4 level changed in parallel with the clinical course of the ovarian cancer. Therefore, our results suggest that measurement of CA 72-4 be combined with measurement of CA 125, so as to provide a better sensitivity and specificity in monitoring an ovarian cancer. PMID- 2232184 TI - [An epithelial myoepithelial carcinoma of the parotid gland]. AB - A case of epithelial myoepithelial carcinoma is reported. Histologically, this tumor shows tubular and solid growth pattern. The inner layer of the tubules is composed of cells with an eosinophilic cytoplasm that is surrounded by cells with clear cytoplasms. Clear cells also manifest a solid growth pattern. Immunohistochemical and electron microscopic examinations has revealed that the cells with an eosinophilic cytoplasm have the characteristics of the ductal epithelium and that the clear cells have the characteristics of the myoepithelium. Immunohistochemically, keratin positive clear cells and S-100 protein positive ductal cells were found in our case. This suggests the existence of cells having both ductal and myoepithelial characteristics and this inspected tumor had derived from multipotential cells of intercalated ducts. PMID- 2232186 TI - [A case of asbestos exposure complicated by a malignant pheochromocytoma]. AB - Reported is a case of non-functioning malignant pheochromocytoma. The patient had an occupational history of asbestos exposure and pleural plaque was seen in the chest X-rays. The tumor appeared from right adrenal gland and its size was 12 x 15 cm, which was measured by CT scanning. This determined to be non functioning because catecholamines in the serum and VMA in the urine were within normal limits. A metastasis of this tumor was seen in the lung, the liver, and the bone. So far as is known, this is the first case of asbestos exposure complicated with malignant pheochromocytoma that has been reported in the Japanese literature. PMID- 2232185 TI - [A basal cell carcinoma of the esophagus--a case report]. AB - Reported is the case of a 58-year-old male who visited our hospital with the chief complaint of anorexia. Diagnosed as having an esophageal cancer, a subtotal esophagectomy was performed including the dissection of the tumor. According to the surgical findings, the tumor was not exposed to the tunica externa and no lymph node metastasis or infiltration to the pleura or a metastasis to the lung or liver was note. On histopathological examination a basal cell carcinoma of esophagus was determined but no squamous epithelium was seen. The carcinoma was the muscular propria, and neither infiltration into the epithelium nor invasion into the vessels was noted. The postoperative progress appeared good, however seven months later the patient died from multiple hepatic metastasis. PMID- 2232187 TI - [Eleven cases of spindle cell carcinoma of the breast, with special reference to cystic changes in the tumor]. AB - The clinicopathological features of 11 cases of a spindle cell carcinoma handled by our department have been investigated and are presented, with two cases that demonstrated cystic changes. Out of a total of 1,524 breast carcinomas that were treated, 11 (0.72%) were spindle cell carcinomas. The size of the tumor was generally larger than in other more common types of breast carcinomas, but the degree of a lymph node metastasis was low and the prognosis was better. As for the ER status, 4 out of 5 cases were negative. As cystic changes in the tumor were found in 5 of the 11 cases, it would seem that spindle cell carcinomas of the breast tend to show cystic changes in their tumors. PMID- 2232188 TI - [A case of type I early gastric cancer discovered after gastrectomy of depressed type early gastric cancer]. AB - Greater clarification has resulted since the discussion at the 38th Stomach Cancer Research Meeting on the frequency of a cancer developing in the remaining portion of a stomach after excision of a previous gastric cancer. Further, fewer reports have appeared of early stage cancers in the remaining stomach. Reported here is a case of a patient with an early stage stomach cancer, type I, that occurred 5.5 years after resection of an early stomach cancer, type IIc + III, at a point some distance removed from the anastomosis of the remaining stomach. Total extirpation of the remaining stomach resulted. Two years later, surgery to remove a pulmonary small cell carcinoma in this patient also was performed. The paper presents a study of this case. PMID- 2232189 TI - [Gastric cancer presenting a variety of macroscopic and histopathological findings]. AB - A 68-year-old man was admitted to hospital because of nausea and vomiting. Examination of the upper digestive tract led to a total gastrectomy. A histopathological examination revealed a Borrmann type 3 advanced cancer in the prepyloric antrum that showed a moderately differentiated adenocarcinoma. Found on the anterior wall of the middle corpus was an advanced cancer, mimicking a type IIc early cancer, that was poorly differentiated with dispersed signet ring cells. Between these two advanced cancers, another superficially extended cancer, consisting of a type IIa and IIb early cancer, was found. The type IIa cancer, located on the posterior wall of the angle, was a papillary adenocarcinoma and the type IIb cancer on the lesser curvature of the antrum was moderately differentiated. Therefore this patient displayed not only a type IIa and a type IIb cancer, but also a Borrmann type 3 cancer and an advanced cancer, mimicking type IIc, that were linked into one large lesion. Although the present case was not determined as being a multiple gastric cancer, it suggests the likelihood of a multicentric generation, growth, and extension of synchronous multiple cancers, in view of the variety of macroscopic and histopathological findings presented. PMID- 2232190 TI - [A case of triple carcinomas: stomach carcinoma surgically removed, renal tumor, and carcinoma of the remnant stomach]. AB - Reported is the case of a 57-year-old male patient, who manifested tarry stool and who had undergone a subtotal gastrectomy at our hospital in 1983 for an early carcinoma, type IIc, which proved to be a well differentiated tubular adenocarcinoma. Three years later, he returned complaining of epigastralgia, although no evidence of a recurrence could be seen. An abdominal ultrasonogram and a CT scan, however, revealed a right renal tumor and he subsequently underwent an operation for the removal of a renal cell carcinoma, a clear cell type. In 1988, he again was readmitted to hospital, this time because he easily became fatigued. An upper GI series and gastroscopy located a polypoid lesion in the remnant stomach. Thus, a total gastric resection was performed, and the lesion was diagnosed as being a well differentiated tubular carcinoma, an early gastric cancer, type I. Triple carcinomas are very rare, and the details of this case are discussed. PMID- 2232191 TI - [A case of complete remission from acute unclassified leukemia achieved by using a prodrug of ara C, stearyl-ara-CMP (YNK01)]. AB - YNK01 (a daily oral dose of 450 mg) was administered for 22 days to a 58-year-old female with Ph1-positive acute unclassified leukemia. Leukemia cells were negative for peroxidase and esterase, but were positive for CD19, CD13, CD34, CD9, HAL-DR, CD25, and TdT. Complete remission was obtained and continued for at least a month. The main side effects noted were diarrhea and melena. The administration of YNK01 resulted in plasma ara C levels that ranged between 15.4 to 23.0 ng/ml, which appear to be nearly equivalent to dose achieved during continuous IV infusion of a low dose (20 mg/m2/day) of ara C. PMID- 2232192 TI - [Advance in bone marrow transplantation and bone marrow donor registry in the world]. PMID- 2232193 TI - [MHC-restricted antigen recognition by T cells]. PMID- 2232194 TI - [Clonal anergy as a mechanism of transplantation tolerance]. PMID- 2232195 TI - [Roles of non-MHC genes in the induction of graft-versus-host reaction]. PMID- 2232196 TI - [Advances in hematopoietic growth factor research and bone marrow transplantation -hematopoietic stem cells and their growth factors]. PMID- 2232197 TI - [Application of recombinant hematopoietic factors for bone marrow transplantation]. PMID- 2232198 TI - [The process of hematological reconstitution after human bone marrow transplantation]. PMID- 2232199 TI - [T cell depletion for allogeneic bone marrow transplantation]. PMID- 2232200 TI - [Graft-versus-leukemia effect (GVL effect): pathophysiological and clinical aspects]. PMID- 2232201 TI - [Physical and radiobiological considerations of total body irradiation and total lymphoid irradiation for bone marrow transplantation]. PMID- 2232202 TI - [HLA-mismatched bone marrow transplantation]. PMID- 2232203 TI - [Indications of allogeneic bone marrow transplantation]. PMID- 2232204 TI - [Schedule for bone marrow transplantation and selection of marrow donor]. PMID- 2232205 TI - [Conditioning regimens for diseases treated by allogeneic bone marrow transplantation]. PMID- 2232206 TI - [Technology of bone marrow transplantation--harvest and manipulation of bone marrow cells]. PMID- 2232207 TI - [Prevention and treatment of various infections after bone marrow transplantation]. PMID- 2232208 TI - [Monitoring of graft versus host (GVH) reaction and host versus graft (HVG) reaction]. PMID- 2232209 TI - [Complications classified under clinical stages following bone marrow transplantation]. PMID- 2232210 TI - [Acute GVHD: pathogenesis, symptomatology, stage/severity, and treatment]. PMID- 2232211 TI - [Immunopathogenesis and clinical aspects of chronic GVHD after allogeneic bone marrow transplantation]. PMID- 2232212 TI - [Allogeneic bone marrow transplantation for acute lymphoblastic leukemia]. PMID- 2232213 TI - [Results and proposal standard for the indication of bone marrow transplantation in acute nonlymphocytic leukemia]. PMID- 2232215 TI - [Bone marrow transplantation for myelodysplastic syndrome]. PMID- 2232214 TI - [Bone marrow transplantation for chronic myelogenous leukemia]. PMID- 2232217 TI - [Ex vivo purging methods for autologous bone marrow transplantation]. PMID- 2232216 TI - [Allogeneic bone marrow transplantation for aplastic anemia]. PMID- 2232218 TI - [Method and clinical results of autologous bone marrow transplantation]. PMID- 2232219 TI - [Autologous bone marrow transplantation in the treatment of solid tumors: current status of clinical results]. PMID- 2232221 TI - [Immunological tests ]. PMID- 2232220 TI - [Antiviral chemotherapy for AIDS: dideoxynucleosides and clinical application]. PMID- 2232222 TI - [Tumor and immunology]. PMID- 2232223 TI - [List of diagnostic reagent kits for immunological tests and review of immunoreplacement, suppressant, modulator and complement control factor]. PMID- 2232224 TI - [Transplantation immunology]. PMID- 2232225 TI - [Aging and immunity]. PMID- 2232226 TI - [Reproduction and immune response (including in pregnancy)]. PMID- 2232227 TI - [Clinical immunology in various field of medicine]. PMID- 2232228 TI - [Immunosuppressive therapy ]. PMID- 2232229 TI - [Basic concept and clinical application of monoclonal antibody]. PMID- 2232230 TI - [Thrombospondin]. PMID- 2232231 TI - [Plasminogen activator inhibitor-2]. PMID- 2232232 TI - [Molecular basis for hereditary deficiency of alpha 2-plasmin inhibitor]. PMID- 2232233 TI - [Studies on the pathogenesis of hypercoagulability in patients with arterial thrombosis and malignancy]. PMID- 2232235 TI - [The tissue factor activity in plasma in patient with DIC]. PMID- 2232234 TI - [Abnormality of blood coagulation before onset of DIC--risk factors for DIC]. PMID- 2232236 TI - [Plasma level of activated factor IX-antithrombin III complex in hypercoagulable state]. PMID- 2232237 TI - [Leukemia and pre-DIC--coagulation and fibrinolytic parameters in severe infection at the nadir of leukocyte after chemotherapy]. PMID- 2232238 TI - [Protein C--possible usefulness as a therapeutic weapon]. PMID- 2232239 TI - [Mechanism of platelet activation induced by TP 82, a monoclonal antibody against CD9]. PMID- 2232241 TI - [Congenital factor IX abnormalities]. PMID- 2232240 TI - [Binding of calpain to plasma membrane and its role in platelets]. PMID- 2232243 TI - [Structure, function and expression of human tissue factor]. PMID- 2232242 TI - [Structure and function of von Willebrand factor: GPIb binding domain]. PMID- 2232244 TI - [Progress in clinical chemistry]. AB - The basic and clinical studies that are expected to influence future laboratory medicine were presented by five speakers in the symposium held at the National Cardiovascular Center, in Osaka on January 27, 1990. Dr. Y. Katayama reported a new method for analyzing glycated protein by HPLC and the data on the positive error caused by superoxide anion in the value of fructosamine. Dr. Y. Harano described a sensitive method for enzyme immunoassay of apoprotein B and discussed cases of diabetes mellitus, hyperlipidaemia and hypo-apoprotein B with respect to the apoprotein B level. Dr. T. Noguchi reported the excellent results in DNA analysis of pyruvate kinase. Dr. N. Taniguchi presented a basic study on superoxide dismutase and noted the increased activity of this enzyme in certain diseases. The assay of this enzyme activity can now be routinely performed. Dr. H. Matsuo, the last speaker in this symposium, had received the Gakusiin award in 1989 for his studies on atrial natriuretic hormone (ANH). He outlined the history of ANH study developed in his laboratory. ANH also will be added to routine assay. We, the chairmen in this symposium, added comments concerning useful modern techniques for the clinical chemistry and the role of the clinical laboratory in large hospitals. PMID- 2232245 TI - [Highly sensitive apo B assay and its clinical significance]. AB - Two sensitive and accurate methods for the determination of apo B using polyclonal antibody for human purified LDL are reported. Modified one step EIA by sandwich method is highly sensitive and serum has to be diluted by 1,000-3,000 times, but suited for the diagnosis of hypo or abetalipoproteinemia, detailed analyses of lipoprotein subfractions and in vitro study of lipoprotein metabolism. Latex method is moderately sensitive (serum dilution: 100 times), automated, simple and accurate with CV, 1.5-2.5%. Serum apo B assay is useful not only for the diagnosis of hyperlipidemia, hypolipidemia, but also for the analyses of atherogenic lipoproteins which are frequently associated with large vessel atherosclerotic changes in diabetes, obesity and coronary, cerebral or peripheral vascular diseases. A family pedigree of elevated apo B with frequent association of diabetes (type 2 b) and prominent hypercholesterolemia with autoimmune apo B antibody has been described. In obesity, either hyperinsulinemia or hyperglycemia plays a role in the elevation of VLDL and IDL probably through hepatic overproduction of VLDL. The size of VLDL tends to be larger in VLDL while IDL and LDL seem to become smaller judging from relative lipid contents to apo B. PMID- 2232246 TI - [Regulation of pyruvate kinase gene expression and its clinical application]. AB - Pyruvate kinase (PK), an important glycolytic enzyme, has two genes per haploid genome in mammals and each gene encodes two isozymes. The L gene produces the L- and R-types using alternative promoters. The M gene generates the M1- and M2 types by alternative RNA splicing. Expression of the PK isozymes is tissue specific and regulated developmentally. Carcinogenesis apparently reverses the developmental process. Expression of the L-type is regulated by dietary and hormonal factors. These regulations occurred at post-transcriptional as well as transcriptional levels. The transcription of hepatic L-type PK is stimulated by insulin and inhibited by glucagon. The insulin action requires ongoing protein synthesis and metabolism of glucose, and is enhanced by glucocorticoid. Dietary fructose also stimulates expression of the L-type in liver, kidney, and small intestine, but its mechanism is dependent on tissues, and on plasma insulin levels in the case of the liver. In normal liver, the fructose induction is explained by stimulation of gene transcription. On the other hand, fructose acts mainly at the post-transcriptional level in diabetic liver and other tissues. These fructose effects are attributable to common metabolite(s) of fructose and glycerol. Studies on transgenic mice indicate that the 5'-flanking region up to 3 kb of the L-type PK gene contains cis-acting elements responsible for insulin regulation and tissue-specific expression of the L-type. Further analysis using a transient expression assay revealed the presence of multiple elements necessary for expression of the L-type in hepatocytes in the region up to -170b.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232247 TI - [Superoxide dismutases: significances in aging, diabetes, ischemia and cancer]. AB - Superoxide dismutases (SOD) and their changes in diabetes, aging, ischemia and cancer were studied, Cu, Zn-SOD undergoes glycation reaction in vitro and in vivo and loses its activity by formation of Amadori compounds. Two lysine residues of Cu, Zn-SOD, Lys-122 and Lys-128 are primary glycated sites which are located on the surface of the molecule. The sites are also located on the active site liganding loop which plays a major role in the activity. The glycated Cu, Zn-SOD increased in the red cells of diabetic patients, especially those with diabetic complications. Mn-SOD appears in the serum of patients with acute myocardial infarction in a biphasic manner. The enzyme appears in sera 16 hr and 108 hr after the attack as determined by ELISA. The Mn-SOD levels are also increased in the serum of patients with epithelial ovarian cancer and it is a good marker for detecting and monitoring this cancer. Mn-SOD may play an important role in the ischemic and cancer tissues. PMID- 2232248 TI - [Development of ELISPOT assay for thyroid autoantibody-producing cells]. AB - A new assay system for detection of thyroid-autoantibody-producing cells was developed. This assay is based on the ELISPOT method with antigen-coated nitrocellulose membranes in 96-well microfilter plates. This was more sensitive than conventional methods such as a radioimmunoassay and a passive agglutination method for detection of thyroid-autoantibody production. The coefficients of inter- and intra-assay variations for antibody-producing cells were less than 6.5%. Thus, this assay system can be used to analyse the thyroid-specific immunological abnormalities as a routine test. PMID- 2232249 TI - [The significance of autoantibodies coexisting with anti-centromere antibodies in sera of patients with primary biliary cirrhosis]. AB - Anti-centromere antibody (ACA) has been believed to be specific to patients with CREST syndrome, a variant of scleroderma (PSS). This study was undertaken to clarify the distribution of ACA in various diseases and the significance of autoantibodies coexisting with it. The sera of patients with primary biliary cirrhosis (PBC) along with collagen diseases and aged subjects were examined for ACA by immunofluorescence method (IF) using cultured HEp-2 cells and chromosomes prepared from K 562 cells. ACA were found in sera of 10 patients with PBC, one with scleroderma, one with cerebral infarction and one with chronic renal failure respectively. ACA positive sera were examined for antibodies against other nuclear antigens including nRNP, Sm, Scl-70, SS-A and SS-B and cytoplasmic antigens by double immunodiffusion methods using rabbit thymus extract etc. as the antigens and by IF method using cryostat sections of rat kidney and stomach. In 13 sera with ACA, antimitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA) and anti SS-A antibody were found in 10, 4 and one sera respectively. In 10 PBC patients with ACA, various collagen disease-related disorders were found to coexist; CREST syndrome in one, CRST syndrome in one, Raynaud's phenomenon in two and Sjogren's syndrome in 5. These results would indicate that ACA may be one of the common serological abnormalities among patients with PBC, CREST syndrome and Sjogren's syndrome. PMID- 2232250 TI - [Determination of hepatitis B virus pre-S 2 antigen by reversed passive hemagglutination and its clinical significance]. AB - Pre-S 2 antigen has been distinct as one of the hepatitis B virus (HBV) markers recently. We detected Pre-S 2 antigen by reversed passive hemagglutination (R PHA) in 98 samples and investigated the correlation between Pre-S 2 antigen and other HBV markers. Forty-two samples in 98 surface(s) antigen positive samples were positive for Pre-S 2 antigen (42.9%). Nineteen samples in 21 e antigen positive samples and 20 samples in 74 e antibody samples were positive for Pre-S 2 antigen (90.5% and 27.0% respectively). Pre-S 2 antigen titers by half quantitative 2n dilution method ranged from 256 to 2048 or more in e antigen positive samples and from 8 to 64 in e antibody positive samples. They showed two peak distributions. There were no significant correlation between Pre-S 2 antigen titers and GPT values. In conclusion, determination of Pre-S 2 antigen might be one of the useful indexes of proliferation of HBV. PMID- 2232251 TI - [Plasma concentration of polymorphonuclear leukocyte elastase-alpha 1-proteinase inhibitor complex in patients with gastric ulcer]. AB - To test the possible participation of activated leukocytes in the pathogenesis of gastric ulcer, plasma levels of polymorphonuclear leukocyte-elastase-alpha 1 proteinase inhibitor complex (PMN-EC), a discerning indicator for the activation of leukocytes, were determined in patients with gastric ulcer. Plasma levels of PMN-EC in patients with gastric ulcer (185.2 +/- 21.6 micrograms/l, mean +/- S.E.M.) were significantly higher than those in normal healthy subjects (67.6 +/- 4.4 micrograms/l, p less than 0.01). On the other hand, plasma levels of C reactive protein and sialic acid increased in only 17.8% and 7.1% of patients with gastric ulcer, respectively. No significant correlation was observed between PMN-EC and the plasma levels of CRP or sialic acid. Plasma levels of PMN-EC decreased with the healing of the ulcerative lesion as judged by gastro endoscopic observation. These findings suggested that activation of leukocytes might deeply be correlated with the pathologic mechanism of gastric ulceration and the measurement of PMN-EC might be useful for monitoring the patients with gastric ulcer. PMID- 2232252 TI - [Population pharmacokinetic analysis of indocyanine green retention rate at 15 minutes]. AB - Using the population pharmacokinetic (Bayesian) method, we investigated the indocyanine green (ICG) retention rate at 15 minutes (R 15) in patients with liver disease. For the Bayesian analysis, the mean and variance of parameters, the disappearance rate (K) and the distribution volume, were calculated by the one compartment analysis with data of inpatients. The mean value of the disappearance rate (K) was shown to be smaller and the variances of parameters of the patients were larger than normal values reported, so that it was suggested that the studied group included patients with various kinds of liver diseases. Accordingly, the Bayesian analysis was performed using above statistical results. The distribution volumes, calculated from three points measurements by Bayesian method, were estimated smaller and the initial concentrations higher than those obtained by the one compartment analysis. However, the retention rate (R 15) were well correlated the results of one compartment analysis. The Bayesian analysis using one point measurement at 15 minutes, resulted that the values of retention rate (R 15) were shown about 17% lower, but well correlated with the coefficient gamma = +0.9972 to those obtained by usual method. The disappearance rate (K), which calculated simultaneously from the one point analysis, showed the lowest value on liver cirrhosis. So that, the application of Bayesian analysis to the one point measurement of ICG test was useful to clinical evaluation of liver disease. PMID- 2232253 TI - [Chromosome abnormalities in myelodysplastic syndrome]. AB - We performed chromosomal analysis in 18 patients with myelodysplastic syndrome (MDS). According to the French-American-British (FAB) cooperative study group and Research Group of Japanese Ministry of Welfare Classification, our cases with MDS were classified into four subtypes as follows; refractory anemia [RA], 6 cases; refractory anemia with excess of blasts [RAEB], 4; chronic myelomonocytic leukemia [CMML], 3; refractory anemia with excess of blasts in transformation [RAEB-T], 4; and refractory cytopenia [RC], 1. Thirteen patients (72%) had chromosomal abnormalities and frequently observed chromosomal abnormalities were trisomy 8, -7/7q-, 20q-, trisomy 1q and 5q-. The mean survival were as follows; RA: 22.5 months, RAEB: 13.2 months, CMML: 15 months, RAEB-T: 5.5 months. Progression to overt leukemia occurred in 5 patients (27.7%): 1 of four patients with RAEB, 1 of three patients with CMML and 3 of four patients with RAEB-T. In conclusion, chromosomal abnormalities were most frequently observed in the patient with RAEB-T who had shortest survival time among the patients with MDS. On the other hand, chromosomal abnormalities were less frequently observed in the patients with RA and they showed relatively better prognosis than the other types of MDS. PMID- 2232254 TI - [Serum adenosine deaminase and its isozyme activity in leukemia and MDS]. AB - We studied the activity of serum adenosine deaminase (ADA) and its isozyme in 36 leukemic patients (16 ANLL, 11 ALL, and 9 CML) and 8 MDS. Isozyme was measured by erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibitory assay. This assay was simple and reliable. The appearance rate of abnormally high ADA value were 81.24% for ANLL, 100% for ALL, 77.8% for CML and 37.5% for MDS. The ADA level became high when MDS turned into overt leukemia. In isozyme pattern, there was a clear difference between ANLL and ALL. The isozyme I/II ratio was significantly higher (p less than 0.001) in ALL than ANLL. Lymphoblastic crisis of CML also had a high isozyme I/II ratio. There was a correlation between isozyme I and absolute number of peripheral blasts in ALL (r = 0.768). When observed time sequentially, ADA and isozyme changed correlatively with the number of blasts counts. Serum ADA and its isozyme are useful parameters both for leukemic diagnosis and treatment. PMID- 2232255 TI - [Serum and urinary cell growth factors in non-insulin-dependent diabetes mellitus]. AB - Serum very low molecular weight growth factor like-activity (S-VLMGA, molecular weight less than 3,000) and serum and urinary epidermal growth factor (S-, U-EGF) were investigated in 180 patients of non-insulin-dependent diabetes mellitus (NIDDM) by bioassay using skin fibroblast cells (CCD-27 SK) and enzyme- and radio immunoassay, respectively. S-VLMGA was slightly elevated in NIDDM patients with retinopathy (RET) and/or neuropathy (NEU), but slightly decreased in those with nephropathy (NEP) compared with patients without complications, though the differences were not significant (without complications: 122 +/- 9, with RET and/or NEU and without NEP: 145 +/- 15, all with NEP: 110 +/- 8% of increased growth activity, mean +/- SE). The similar tendencies were seen in S- and U-EGF in the same groups. However the changes in S-EGF were small and the decrease of U EGF in patients with NEP was remarkable (U-EGF of without complications: 22.7 +/- 2.5, with RET and/or NEU and without NEP: 24.5 +/- 4.2, all with NEP: 17.6 +/- 3.2 ng/mg creatinine, mean +/- SE). Furthermore, S-VLMGA was inversely, but U-EGF was positively related with the creatinine urinary vs serum ratio. Thus the concentrations of VLMGA and EGF in serum and urine depend on a renal permeability. PMID- 2232256 TI - [Identification and susceptibility of clinically isolated yeast-like fungi]. AB - We studied the identification and susceptibility of clinically isolated yeast like fungi at Showa University Hospital from April 1988 to March 1989. Clinically significant of yeast-like fungi were observed in 7.1% of specimens from outpatients, 13.0% of inpatients. In both outpatients and inpatients, yeast-like fungi were isolated mainly from sputum and urine. But, one third of them were considered as non-pathogenic and not identified. The species of isolates were, Candida albicans 57%, Candida tropicalis 14% and Candida glabrata 8% in both inpatients and outpatients, and these species shared most part. The isolation frequency of Candida parapsilosis was higher in blood and cerebrospinal fluid (CSF) specimen than the others. The susceptibility test by agar dilution method indicated most of the isolates were susceptible to Amphotericin B and Miconazole (MIC less than or equal to 25 micrograms/ml). There was no difference in MIC between predominantly isolated fungi and commonly isolated fungi. Notably, isolates from blood and CSF showed a significant high tolerance against Amphotericin B and Miconazole than from the other specimens. The MICs of Fluconazole were shown to be very high (greater than 100 micrograms/ml) in normal Sabouraud agar, were decreased dose-dependently by human sera in the medium. These findings indicated the component(s) of sera enhanced the anti-fungal activity of Fluconazole. PMID- 2232257 TI - [Study of chromogenic substrate on protein C activity assay--in patients treated with warfarin]. AB - Protein C is an anticoagulant protein that circulates in blood as a zymogen of a serine protease. Recently the exogenous Protein C activator has been obtained from the venom of Agkistrodon Contortrix Contortrix. We also reported a functional assay method which activates Protein C with PROTAC and then measure the amidolytic activity with chromogenic substrate (S-2366) by COBAS FARA. At present, S-2366 (Glu-Pro-Arg-pNA), CBS 65-25 (Lys-Pro-Arg-pNA) and SPECTROZYME PCa (Lys-Pro-Arg-pNA) are used as the chromogenic substrate for activated Protein C. We studied which substrate is more suitable for amidolytic activity assay for Protein C by PROTAC in 99 patients under long-term Warfarin therapy and 29 as normal subjects. Our results indicate that SPECTROZYME PCa and CBS 65-25 are unsuitable for Protein C activity assay with PROTAC. Because change of absorbance was detected in Protein C deficient plasma and we couldn't gain good correlation between amidolytic activity of activated Protein C measured with these chromogenic substrates and antigenicity of Protein C by EIA. On the other hand, S 2366 is the most specific for activated Protein C and we also obtained good correlation against Protein C antigen. PMID- 2232258 TI - [A resected case of mucin-secreting malignant papillomatosis (villous tumor) of ductus choledocus and left intrahepatic duct]. AB - A resected case of remarkably mucin-secreting malignant papillomatosis (villous tumor) of the ductus choledocus and left intrahepatic duct in a 79 year-old female was reported. In this case, cholecystectomy and choledocho-duodenal anastomosis for the gallbladder stone were performed 14 years ago. Villous or papillary tumors arose in the ductus choledocus and spread into the left intrahepatic duct. Histological examination revealed villous proliferation similar to the villous tumor in the large intestine, in which cancerous and adenomatous changes intermingled showing remarkable mucin secretion. Tumor invasion was limited in the wall without extracanal dissemination, and nodal metastasis was absent. Interestingly, exceeding mucin-secretion was observed as the frog-egg like appearance in the ductus choledocus and as the regurgitation into the stomach by the endoscopic examination. This type carcinomas usually show favorable prognosis compared with the ordinary adenocarcinomas of the bile duct. PMID- 2232259 TI - [Cerebral blood flow and event-related potential in patients with cerebral infarction]. AB - Cerebral blood flow (CBF) and P 300, a long-latency positive component of the scalp-recorded event-related potential (ERP) associated with cognitive processing were investigated in patients with cerebral infarction to elucidate the relationship between CBF and cognitive function. Twenty-five patients with cerebral infarction with a mean age of 66.8 years were studied. ERP was recorded during auditory discrimination tasks. The latency of the P 300 from Pz region was recorded. The regional CBF was measured by the 133Xe inhalation method. The F1 (cortical gray matter flow) values were calculated using the Obrist's method. The mean F1 values in patients with cerebral infarction were significantly lower compared to the values obtained for the 15 control subjects (mean age, 68.4 years) (p less than 0.01). Patients with cerebral infarction showed significant prolongation of the P 300 latency compared to the 20 control subjects (mean age, 64.4 years) (p less than 0.02). There was a significant correlation between the P 300 latency and the mean F1 values in patients with cerebral infarction (p less than 0.01). Present results suggest that the cognitive impairment with respect to ERP may be related to the reduction of cortical blood flow in patients with cerebral infarction. PMID- 2232260 TI - [Mitral valve prolapse syndrome as an etiologic factor of anxiety disorder]. AB - To assess whether a certain somatic disease is involved in the etiology of anxiety disorder, we examined the relationship between anxiety disorder and mitral valve prolapse syndrome (MVP). Patients with anxiety disorder were diagnosed according to the criteria of the American Psychiatric Association (Quick Reference to the Diagnostic Criteria from DSM-III). Two-dimensional echocardiography was carried out on 36 normal controls (15 males and 21 females) and 39 patients with anxiety disorder (19 males and 20 females); including 21 patients with panic disorder, 12 with generalized anxiety disorder, and 6 with atypical anxiety disorder. The echocardiograms were evaluated by a cardiologist unaware of clinical background about these patients. The presence of MVP was diagnosed according to the criteria by Yoshikawa, et al. or Nagata, et al. Findings of MVP were seen in 18 (46.1%) of the patients and 5 (13.9%) of the controls indicating a significantly higher incidence (chi 2 = 7.711, p less than 0.01) in the patients. In the patient subgroups, 14 patients with panic disorder (66.6%) and 4 with generalized anxiety disorder (33.3%) had MVP, showing a significantly higher incidence in the former (chi 2 = 14.335, p less than 0.01) than in the normal controls, but no statistical significance in the latter. No MVP was found in the patients with atypical anxiety disorder. These results suggest that some somatic diseases such as MVP may play a role in the etiology of anxiety disorder, especially panic disorder. PMID- 2232261 TI - [In vitro thermosensitivity of various human tumors evaluated using the SDI (succinate dehydrogenase inhibition) test]. AB - In vitro thermosensitivity of various human tumors including 90 esophageal, 10 gastric and 40 colo-rectal cancers were evaluated using the succinate dehydrogenase inhibition (SDI) test. Tumor fragments minced with scissors were incubated at 43 degrees C as heat treated cells and at 37 degrees C as controls for 20 hrs, and assayed for the succinate dehydrogenase (SD) activity using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) as a hydrogen acceptor. The thermosensitivity was estimated by the percentage of SD activity of heat treated cells compared to that of each control. A variation in the thermosensitivity was noted between patients. The SD activity was 60.1 +/- 20.3% (mean +/- standard deviation) for esophageal cancers, 34.9 +/- 21.7% for gastric cancers, 50.3 +/- 20.6% for colo-rectal cancers. Significant differences were noted between esophageal cancers and gastric cancers, colo-rectal cancers (p less than 0.01 and p less than 0.05, respectively). When the thermosensitivity was arbitrarily defined as reduction in the SD activity to 50% of control or less, the positive rates were 31.1% for esophageal cancer, 70% for gastric cancer and 62.5% for colo-rectal cancer. Our results show that the SDI test is a useful method for determination of the thermosensitivity of clinical samples. PMID- 2232263 TI - [Molecular basis of mucopolysaccaridosis type VII (beta-glucuronidase deficiency)]. AB - We have identified several mutations causing beta-glucuronidase (beta Gl) deficiency in three cases with mucopolysaccaridosis type VII (MPS VII). Enzyme assay of lysates of these lymphocytes or cultured fibroblasts showed little residual activity and that the beta Gl-specific mRNA levels were normal, as revealed by Northern blot analysis. Mutated cDNA clones including the entire coding sequencing were isolated from a library in case 1 and PCR (polymerase chain reaction) products in case 2 and 3 derived from cultured fibroblasts. Sequencing of the full-length mutated cDNA revealed C----T transitions, an event causing a single Ala619----Val change (cases 1 and 2) and Arg382----Cys and Pro649----Leu changes (case 3). The former change is detected by loss of the cleavage site for the enzyme Fnu 4 HI in the mutated cDNA. On the basis of the loss of Fnu 4 HI restriction site, the patients (cases 1 and 2) were shown to be a homozygote with this mutation and the parents and brother in case 1 were heterozygotes. The Ala619----Val and Arg382----Cys mutations disrupt a functional domain consisting of a region of sequence highly conserved among human, rat and bacterial beta Gl's, and they lower the enzyme activity, as tested by transfection of COS cells with expression vectors harboring the mutated cDNA. However the Pro649----Leu mutation does not lower the enzyme activity. PMID- 2232262 TI - [Methicillin-resistant Staphylococcus aureus (MRSA) infection--significance of MRSA in respiratory tract infection]. AB - We have examined background factors in MRSA infection in cases in which S. aureus had been isolated from sputa. The incidence of isolation of S. aureus was high and still increasing in expectorated sputa, and causative organisms in the cases of pneumonia and autopsied lungs. A significant correlation was observed between high incidence of isolation of S. aureus and abuse of third-generation cephems. MRSA isolation rates of inpatients was higher than that of outpatients. Among the inpatients such cases with severe underlying diseases and prolonged admission showed the highest incidence of isolation of MRSA. There seemed to be a correlation between distribution of patients with S. aureus and that of rooms with S. aureus in the air. This suggests nosocomial infection. Although MRSA was frequently isolated from sputa, most cases showed no signs of infection, and this suggested that they had been transient colonization. Such antimicrobial agents as rifampicin, teicoplanin, vancomycin reveal excellent antibacterial activity against MRSA and minocycline, ofloxacin were moderately effective. The physician must be informed of the significance of MRSA, because their understanding of MRSA still remains insufficient. PMID- 2232264 TI - [Detection of serum hepatitis B virus DNA using the polymerase chain reaction assay]. AB - We compared the sensitivity of the polymerase chain reaction (PCR) assay to that of slot blot hybridization for detecting hepatitis B virus (HBV) DNA in the serum of a chimpanzee infected with HBV and 52 patients. Also, we utilized a rapid PCR procedure for the detection: Viral DNA was released from virions by incubating serum with NaOH. After a primary PCR amplification, the sample was reamplified using a second set of primer pairs (PCR/PCR). In the chimpanzee, HBV DNA was detected 3 weeks earlier than the appearance of hepatitis surface antigen (HBsAg) and persisted for two weeks with antibody to HBsAg. Of the 14 chronic hepatitis B patients positive for both HBsAg and HBV e antigen (eAg), 9 were positive for HBV DNA by slot blot hybridization and all 14 by PCR. Also, of 9 patients positive for HBsAg and antibody to eAg, 2 were positive for HBV DNA by slot blot hybridization and 8 by PCR. Three of the 11 patients who had lost HBsAg during follow up examination of chronic hepatitis B were positive for HBV DNA by PCR, whereas none of them was positive by slot blot hybridization. Six patients who had recovered from acute hepatitis B more than one year ago and 12 cases who had had vaccination of HBV were negative for HBV DNA by PCR. This technique should yield valuable information on the biology of HBV. PMID- 2232265 TI - [Molecular diagnosis of inherited coagulation disorders--sequence analysis of hemophilia B patients with anti-factor IX antibodies]. AB - Seven hemophilia B patients with anti-factor IX antibodies are studied with molecular means. A total factor IX gene deletion was detected in four patients from three distinct families. Three other patients without detectable gene arrangements were investigated at the DNA sequence level. Enzymatic amplification of the factor IX gene and subsequent DNA sequencing revealed four novel nucleotide mutations in these patients. Patient HB 5 had two point mutations in his factor IX gene. One is located at nucleotide -793 from the translation start (G-A) and the other (C-T) was found in the codon for 191-Gln changing to a termination codon. Patient HB6 had a point mutation (G-A) in the splicing junction of intron g. A2 bp nucleotide deletion was detected in the third exon of the patient HB7 yielding 8 frameshifted amino acids and a stop codon. These results suggested that not only a large deletion of the factor IX gene but also point mutations or small deletion of the gene which may cause the substantial loss of the coding information for the mature protein are involved in the development of anti-factor IX antibodies in hemophilia B patients. PMID- 2232266 TI - [Quantitative estimation of malignancy of gastric cancer by DNA ploidy and proliferative activities]. AB - Paraffin-embedded tumor samples from 493 patients with gastric cancer were analyzed by DNA flow cytometry, and proliferative activities of 155 tumors were measured by bromodeoxyuridine (BrdU) labeling, Ki-67 monoclonal antibody (Mab), and anti-p105 Mab. The results were correlated with clinicopathological findings and patients prognoses. Of the 493 patients, 183 (37%), 225 (46%), and 85 (17%) showed diploid, single DNA a neuploid, and DNA-multiploid. The relative risk of death was three-fold higher in DNA-multiploid tumors than in DNA-diploid tumors. BrdU labeling indices also proved to be an independent prognostic factor. Multiploid tumors had the highest median BrdU LI associated with the most frequent lymph node metastases and hepatic metastases. When the DNA histogram and all the clinicopathological parameters were entered simultaneously into the Cox regression model, DNA ploidy, hepatic metastasis, peritoneal dissemination, BrdU LI, and nodal status emerged as independent prognostic parameters. These results indicate that DNA ploidy and proliferative activities may be useful prognostic factors for the patients with gastric cancer. PMID- 2232268 TI - [Studies on faint attack due to arrhythmias with Holter electrocardiogram]. AB - Out of 1,400 Holter ECGs, 15 records revealed arrhythmias which would be responsible for faint attack, including 8 sick sinus syndrome with cardiac arrest, 4 non-sustained ventricular tachycardia (VT), 2 paroxysmal atrial fibrillation and 1 paroxysmal supraventricular tachycardia. All of cardiac arrest corresponding to faint attack lasted for longer than 4 sec, and an averaged duration of the arrest was 5.8 +/- 2.3 sec. This was significantly longer than that with no subjective symptoms, 3.4 +/- 0.7 sec. Duration and rate of VT did not show any significant relationship with faint attack. The result suggests that cardiac arrest is mostly responsible for arrhythmia-induced involvement of cerebral circulation and faint attack. It is also suggested that cardiac arrest longer than 4 sec should be extensively treated including pacemaker implantation. PMID- 2232267 TI - [Structural analysis of abnormal hemoglobin by the polymerase chain reaction (PCR) of genomic DNA]. AB - Determination of the primary structure of abnormal Hbs on the basis of DNA sequencing of the globin gene obtained from a carrier of abnormal Hb was performed. DNA obtained from the leukocytes of the peripheral blood was amplified by the polymerase chain reaction (PCR) using the proper amplification primer set. Amplified DNA was digested with two different restriction endonucleases and cloned to vector M 13 mp 18 or mp 19, which had been digested with the same enzymes. DNA sequencing was done by the dideoxy chain termination method using T 7 DNA polymerase, and the abnormal Hbs whose primary structure was determined were as follows: Hb Fukuoka [beta 2 His(CAC/T)----Tyr(TAT)], Hb Machida [beta 6 Glu(GAG)----Gln (CAG)], Hb Hope [beta 136 Gly(GGT)----Asp(GAT)], Hb Hiroshima [beta 146 His(CAC)----Asp(GAC)] and Hb Kodaira [beta 146 His(CAC)----Gln(CAA)]. This method for determining the primary structure of abnormal Hbs might be more effective than the ordinary method, which involves amino acid analysis and amino acid sequencing of the abnormal peptide obtained from abnormal Hb. PMID- 2232269 TI - Basic and clinical aspects of methicillin-resistant Staphylococcus aureus (MRSA). PMID- 2232270 TI - [Present status of methicillin-resistant Staphylococcus aureus and susceptibility to antimicrobial agents in 6 hospitals in Okinawa]. AB - During the period from November 1987 to March 1988, 301 strains of S. aureus isolated from clinical specimens were collected from 6 hospitals in Okinawa main island. Thirty seven percent of the strains were resistant to methicillin (MRSA, MIC greater than or equal to 12.5 micrograms/ml). There was a difference in an isolation frequency among the hospitals from 13 to 52%. The strains were isolated from pus, sputum and urine with high frequency. As coagulase typing of MRSA, Type II and III strains predominantly isolated with 54% and 40%, respectively. Among the antimicrobial agents tested, about 90-99% MRSA were resistant to beta-lactam antibiotics and aminoglycosides and no resistant strain was observed to MINO. To IPM/CS and OFLX, 84% and 75% of the strains were sensitive, respectively. MRSA is a hospital strain and may be a causative microorganism for a hospital and opportunistic infection. PMID- 2232271 TI - [Mechanism of beta-lactam-resistance in methicillin-resistant Staphylococcus aureus]. AB - The role of penicillin-binding protein (PBP) 2' in the expression of beta-lactam resistance was investigated using methicillin-resistant Staphylococcus aureus (MRSA) strains with different level of resistance. Both high- and moderate-level MRSA produced very similar PBP 2' with low affinities for beta-lactam antibiotics. Affinities of antibiotics for PBP 2' (I50, concentration which inhibits [14C] benzylpenicillin-binding by 50%) correlated well with their antibacterial activities (MIC) in a high-level MRSA, but did not in a moderate level MRSA. High-level MRSA contained a larger amount of PBP 2' than moderate level MRSA, and the amount of PBP 2' decreased by increasing the temperature of the culture; the extent of decrease was larger in a strain which was sensitive at 37 degrees C than a strain which exerted relatively high level resistance even at 40 degrees C. A cephamycin-resistant, methicillin-sensitive strain began to synthesize PBP 2' by adding cephamycin-type antibiotics to the medium and consequently acquired resistance to methicillin. Latent MRSA producing no PBP 2' generated clones which produced PBP 2' constitutively and were highly resistant to all beta-lactams. These results suggest that the presence of PBP 2' is critical for the expression of beta-lactam-resistance in MRSA and the degree of the resistance depends mainly on the amount of PBP 2' which differs from strain to strain and is influenced by environments such as temperature and the presence of inducer. PMID- 2232272 TI - [Nosocomial infection with methicillin-resistant Staphylococcus aureus]. AB - Methicillin-resistant Staphylococcus aureus (MRSA) isolated in our hospital between 1986 and 1989 were mainly examined for their susceptibility to various antibiotics and coagulase types. The isolation frequency of MRSA among S. aureus isolated from clinical specimens has been steadily increasing; 37.8% in 1986, 49.8% in 1987, 60.6% in 1988 and 63.2% in 1989. This trend was particularly noticeable in the specimens associated with the respiratory tracts. The isolation rate of MRSA in the surgery and pediatrics wards was higher than that in the internal medicine ward. More than 80% of MRSA were coagulase type II, which were multi-resistant to penicillins, cephems, aminoglycosides and macrolides, and sensitive to MINO, new quinolones and VCM. These epidemic strains were also isolated from the nose of medical staff and from air samples in the wards. These findings suggest that the hospital environment including the patients and hospital personnel is extensively contaminated with multi-resistant MRSA of coagulase type II. Measures should be taken for prevention and control of nosocomial infection with MRSA in the whole hospital. PMID- 2232273 TI - [Methicillin-resistant Staphylococcus aureus infection in the Kagoshima University Hospital--special attention to prevalence in otolaryngological infectious disease]. AB - A retrospective study of the characteristics of MRSA (methicillin resistant S. aureus) in Kagoshima University Hospital and its ENT department was reported. There were 231 samples (104 strains) MRSA in all S. aureus 448 samples from Jan. to Sep. 1989 in Kagoshima University Hospital, in which 58 strains (55.8%) were coagulase type II and 35 strains (33.7%) were type VII. The much more predominant numbers of MRSA were observed in all the cases inpatients clinics in surgery, pediatrics, urology, gynecology and dermatology than internal medicine as well as outpatients clinics. In ENT department of this hospital, only 15.4% of all S. aureus were MRSA. On the other hand, bacteriological survey showed 26% of MRSA out of all S. aureus which were detected at Tokyo clinical research center on otorrhea in the patients with chronic otitis media as multicenter clinical trial of Japan. Two cases involved by MRSA after postoperative administration of many types of antibiotics were also demonstrated. These MRSAs were producing type II coagulase and very high concentrations of MICs to many antibiotics were observed. But these cases were not severe and MINO (minocyclin) or GM (gentamicin) were so effective. The effect of combined therapy of some antibiotics or antimicrobial agents was discussed briefly. PMID- 2232274 TI - [Intravenous DSA as a screening method for cerebral aneurysms]. AB - Intravenous DSA (IVDSA) was evaluated as a screening method for cerebral aneurysms. It was performed 390 times in 372 cases. Clinically useful images were obtained in 94.1% in all examinations. Nineteen aneurysms were visualized in cerebral angiography among 21 cases with SAH or 3rd nerve palsy, whereas in IVDSA 15 aneurysms were noted. Aneurysms not visualized in IVDSA were all 4 mm or less in size. Therefore, aneurysms, more than 4 mm in size, which have higher risks for rupture, were detectable in IVDSA. Based on these findings, IVDSA is considered to be clinically useful in screening for aneurysms. In all 372 cases, 33 aneurysms were suspected in IVDSA findings, whereas in cerebral angiography 21 of them turned to be aneurysms. Such 12 false positive cases were distributed mainly at anterior communicating and middle cerebral arteries. Improvement of image resolution, avoidance of vessel overlapping and proper selection of screened cases should be investigated for further development of this screening method. PMID- 2232275 TI - [CT findings complicating percutaneous nephrostomy, lithotomy and lithotripsy]. AB - Reviews of the CT scans of percutaneous nephrostomy, lithotomy and lithotripsy disclosed 14 out of 78 cases (17.9%) with evidence of complications. Renal and perirenal hematomas were detected in five cases and the other five cases showed collections of contrast material in the retroperitoneum except for the anterior pararenal space. CT demonstrated clearly the anatomic distribution and extent of renal hemorrhage and extravasation of contrast material. Three cases of pleural effusion on CT were accompanied by blood or contrast material collections in the posterior pararenal space. No patients required immediate surgery and CT findings helped the choice of conservative therapies. PMID- 2232276 TI - [MRI of pheochromocytoma]. AB - MRI features of 8 patients were reviewed and correlated with pathological findings. It was characteristic finding that the intensity of pheochromocytoma on T2-weighted image and proton image was very high. The detectability of pheochromocytoma by MRI and CT was almost equal and MRI was also useful for determining aberrant pheochromocytoma. MRI was more helpful for detection of necrotic lesion than CT. We considered that the double ring sign on MRI was characteristic for pheochromocytoma. In the cases which are difficult for diagnosis, other diagnostic studies such as endocrine and other imaging studies are necessary. PMID- 2232278 TI - [MR imaging of the arm]. AB - Thirty arms of healthy adults were studied with MR imaging using surface coil. Fine structures of the arm, such as muscular bundles, small vessels and nerves were clearly demonstrated. Deep fascia dividing muscular bundles appeared as high intensity on T1-weighed image due to fat deposition beneath the fascia. Aponeurosis is also flat sheet of densely arranged collagen fibers. With rather thicker layer of collagen fibers than fascia, aponeurosis appeared as low intensity sheet that was frequently demonstrated on MR images of the extremities. PMID- 2232277 TI - [Non-quantitative analysis of the renography using 99mTc-DTPA; clinical efficacy and limitation]. AB - The purpose of this paper is to evaluate the efficacy and limitation of the non quantitative analysis of renography using 99mTc-DTPA, and to determine the clinical indication of the quantitative analysis of the study. We evaluated the clinical records of the patients and the findings of dynamic imagings and renograms. The non-quantitative analysis of the examination seemed to be useful to the selected cases, and quantitative analysis appeared to be dispensable except for the cases to evaluate the grade of parenchymal damages and causes of asymptomatic hematuria. PMID- 2232279 TI - [Intercostal-pulmonary arterio-arterial fistula with rib notching]. PMID- 2232280 TI - [A case of xanthoma of the skull]. AB - The reports in the radiologic literature of osseous xanthoma are very rare. We reported a case of xanthoma of the skull without hyperlipidemia. The bony changes is well-marginated radiolucent lesion with marginal sclerosis and an central nidus of bone. PMID- 2232281 TI - [Lateral position of the external carotid artery]. AB - Lateral position of the external carotid artery was seen in 17 cases (4.3%), of which 13 cases were on the right side and 4 cases on the left. It is necessary to know the lateral position of the external carotid artery for the correct diagnosis by IVDSA and doppler scanning. PMID- 2232282 TI - [A case of aortitis syndrome]. AB - A 57 years old woman was admitted for the investigation of anginal chest pain. Her coronary angiography didn't show any typical finding seen in the aortitis syndrome, but coronary sclerosis and stenosis seen in the usual atherosclerotic patients. The cerebral angiography was performed, too. The right vertebral artery, which was tortuous and dilated, was seen, but the other three cerebral vessels were not seen. These rare findings were reported in this report. We added the discussion about the relation between the aortitis syndrome and angina pectoris. PMID- 2232283 TI - [Two cases of abdominal bronchogenic cyst]. AB - Two cases of abdominal bronchogenic cyst were reported. In the first case, the cyst was communicated with gastric fundus and existed as gastric abscess. In the second case, the cyst showed high CT number and chemical analysis of the contents revealed high range of Ca, Fe and Amylase levels. PMID- 2232284 TI - [A case report of great omental leiomyosarcoma with perforation into the jejunum]. AB - The case is a 56-year-old woman, who came to our hospital for bloody flux as chief complaint. Small intestine radiography examination revealed findings suspected of jejunal leiomyosarcoma, but selective angiography confirmed a tumor deep-infected image with omental artery alone as arteria nutricia, leading to the diagnosis as omental tumor. PMID- 2232285 TI - [A case of secondary hemochromatosis, in which MRI is useful to evaluate therapeutic effect]. AB - The therapeutic effects of phlebotomy were evaluated by MRI in a case of secondary hemochromatosis. Low intensity of the liver on T1 image remarkably changed and increased after treatment. MRI was very useful to value the changes of iron in the liver. PMID- 2232286 TI - [A case of multiple intrahepatic portosystemic venous shunts associated with multiple hemangioma-like lesions of the liver]. AB - Intrahepatic portosystemic venous shunts (IPVS) are rare, except for the minute ones observed in cirrhotic liver. This report concerns a case with frequent episodes of consciousness loss, diagnosed as IPVS and multiple hemangioma-like lesions of the liver by US, CT and angiography. To our knowledge, this is the first report of association of IPVS and such angiographically evident hemangioma like lesions of the liver. The etiology of IPVS is mostly considered to be congenital though, there are still many arguments about it. The relation between IPVS and the hemangioma-like lesions of the liver is discussed. PMID- 2232287 TI - [Successful emergency superselective embolization for hemobilia with a new coaxial catheter and steerable guidewire]. AB - Hemobilia occurred in a 70 year old female from the left hepatic artery pseudoaneurysm induced by PTBD. A Tracker-18 catheter introduced into the left lateral posterior hepatic artery superselectively and embolization was performed with both sponge gel and Ivalon. This new coaxial catheter system allowed selective occlusion of the hepatic artery pseudoaneurysms with minimal loss of liver function. PMID- 2232288 TI - [A report of renal cell carcinoma in a horseshoe kidney]. AB - A case of renal cell carcinoma associated with horseshoe kidney is reported. The patient was a 67 years old man with the chief complaints of dull pain of right upper abdomen. Ultrasonography (US) revealed horseshoe kidney and abnormal mass sign at the right isthmus of the kidney. By the computed tomography (CT) and angiography, renal cell carcinoma associated with horseshoe kidney was diagnosed. Only 18 cases of this rare disease have been reported in Japan. The diagnostic procedures are discussed and the usefulness of selective arteriography of the isthmus is emphasized, as the presentation of vascular anatomy is of great value for diagnosis, surgical treatment and preoperative arterial embolization. PMID- 2232289 TI - [A case of renal hemangiopericytoma]. AB - The patient is a 33-year-old female. On precontrast CT, the tumor shows a high density area with a low density area. On postcontrast CT, the tumor demonstrates a well-marginated low density area. Angiographically, the tumor shows a hypervascular mass with tumor vessels like a weeping willow and unhomogeneous stain. This is only the fourth such case ever reported before in Japan. PMID- 2232290 TI - [Nuclear DNA content in the cells of squamous cell carcinoma and Bowen's disease. I. Relationship between nuclear DNA content and grade of clinical and histological malignancy]. AB - Nuclear DNA content of squamous cell carcinoma (SCC) was assayed by use of microfluorometry in an attempt to know the relationship between the content and grade of malignancy. As the results, we found that polyploid cell (greater than 4C) population tends to increase with advancing histological malignancy. However, the population of polyploid cells of grade 1, 2 and 3 SCC was almost the same. The number of polyploid cell of recurred lesion of SCC was increased than that of primary lesion. And polyploid cell (greater than GC) population in the primary lesion of the recurred case was higher than that in the tumor of non-recurred case. From these findings, it may be concluded that the polyploid cell population in SCC was proportional to clinical and histopathological malignancy in some extend. PMID- 2232291 TI - [Nuclear DNA content in the cells of squamous cell carcinoma and Bowen's disease. II. A study on DNA contents of deeply invaded cells in comparison with non invading cells at the upper dermis]. AB - To know the variation of DNA contents of SCC cells due to invasion activity, cytophotometric assay was used. The specimens for this study were paraffin embedded tissue section of SCC stained with azocarmin G for blocking the non specific fluorescence. By comparing the nuclear DNA content of tumor cells at the upper dermis and at the subcutaneous fat tissue, it was found that polyploid cells (greater than 4C and greater than 6C) populations in deep tissue was significantly higher than those in the upper dermis. This finding suggests that SCC cells capable to invade deeply are having larger amount of nuclear DNA that cells at the upper dermis. PMID- 2232293 TI - [Generalized granuloma annulare with primary biliary cirrhosis]. AB - Fifty-six year-old woman had a wide spread nodular and papular eruption on the trunk and arms for one week. She had suffered from primary biliary cirrhosis (PBC) for 8 years. The clinical appearance of the eruption was that of generalized granuloma annulare. Skin biopsy revealed a palisading granuloma in the dermis consisting of suppressor/cytotoxic T cells, Langhans type giant cells, plasmacytoid epithelioid cells and phagocytic macrophages with immunohistochemical analysis and electron microscopy. Liver biopsy showed Scheuer's IIIrd stage of PBC without associated granuloma. In PBC granulomata at the portal area of the liver, lung, muscle, skin and so on has been reported. And the histological findings of the granuloma of this case consisted with that of reported cases. Therefore the skin granuloma in this case was assumed to be related to PBC. PMID- 2232292 TI - [Do OKT6 positive Langerhans cells play a role in the suppression of ultraviolet induced carcinogenesis?]. AB - Langerhans cells (LC) in epidermis are antigen presenting cells. LC may play a role in immune surveillance system and are considered to suppress development of ultraviolet (UV) induced skin cancers. We studied effect of UVB irradiation to LC of xeroderma pigmentosum (XP) and normal subjects by using OKT6 monoclonal antibody. When 3 minimal erythema dose (MED) of UVB were irradiated, density of OKT6 positive LC of XP began to decrease 6 hours after irradiation, and showed the least numbers on day 2 and returned completely to the pre-irradiation level on day 14. Further, after 3 MED irradiation, LCs of both normal subjects became the least on day 3 and returned to the pre-irradiation level on day 14. In XP variant and normal subjects, the number of LC in chronic sun-exposed skin decreased significantly in a similar way comparing to that of non-exposed skin. These results suggest that epidermal LC may not play an essential role in prevention of UV-induced tumor development. PMID- 2232294 TI - [Three-dimensional culture of plucked human hair follicles inside the collagen gel matrix]. AB - Plucked human hair follicles were cultured in collagen gel matrix. Epithelial cells, possibly outer root sheath keratinocytes, appeared from the outer root sheath 4 to 5 days after culturing and continually grew into the gel to form spike-like structures for next 3 weeks. The number and size of the spikes differed in each follicle. Autoradiographically, many DNA-synthesizing cells were seen at the outer cell layer in the enlarged outer root sheath and at the edges in the newly formed spike-like structures. The culture method described here appears to be suitable to study the three-dimensional growth, morphogenesis and differentiation of the outer root sheath cells in vitro. PMID- 2232295 TI - [The influence of coptidis rhizoma to lipase activity of Propionibacterium acnes]. AB - Gas chromatography was applied for determination of the amounts of propionic and butyric acids in the medium produced by Propionibacterium acnes. The organism was incubated in Peptone-Yeast extract-Glucose medium containing 0.017 mEq/ml of tributyrin and various amounts of Coptidis Rhizoma at 37 degrees C for 24 to 96 hr. The amount of butyric acid produced by the lipase was reduced parallel with that of propionic acid resulted from the growth of P. acnes in the medium. These facts were also confirmed by counting the cell numbers of P. acnes. Furthermore, any lipase-negative colonies were not observed on the Kishishita's Lipase Medium. These findings indicate that Coptidis Rhizoma inhibits growth of P. acens and anti-lipase activity of the drug against the organism is resulted from the fact. PMID- 2232296 TI - [Esophageal motility and gastric emptying in PSS patients, correlation with symptoms]. AB - Progressive systemic sclerosis (PSS) commonly involves the esophagus. Dysphagia and heartburn are the most common esophageal symptoms. In this study we evaluated the relationship between esophageal symptoms and esophago-gastric motility. On esophageal manometry, loss of peristalsis, peristaltic contraction amplitude of distal esophagus less than 30 mmHg and decreased LES pressure were critical for esophageal symptoms. The degree of symptoms correlated to esophageal dysmotility. The gastric emptying in PSS patients was delayed, but there was no significant difference in gastric emptying between the patients with and without reflux esophagitis. Esophageal dysmotility is considered to be much responsible for the reflux esophagitis in PSS patients than gastric emptying. PMID- 2232298 TI - [Cytoprotection by 16,16-dimethyl prostaglandin E2--role of gastric content and mucus gel layer]. AB - The mechanism of cytoprotection by prostaglandins (PGs) is still unknown, although many hypotheses have been proposed. We postulated a hypothesis that increased gastric content and thickened mucus gel layer by PGs may protect the gastric mucosa against damage from necrotizing agents. Two series of experiments were performed on Wistar male rats, weighing 250-300 g. (1) 16,16-dimethyl prostaglandin E2 (dmPGE2) in doses of 20 micrograms/kg was given orogastrically. Fifteen minutes later, the stomachs were emptied and/or the mucus gel layer removed, and several concentration of ethanol applied. After ten minutes, the stomachs were removed and lesions of the gastric mucosae were evaluated macroscopically and histologically. (2) Volume and pH of the gastric content and mucus thickness were measured 15 minutes after dmPGE2 administration. DmPGE2 did not protect the gastric mucosa against 40% ethanol in the emptied stomach. This agent had no cytoprotective action on the emptied and mucus gel-removed stomach in 30% ethanol application. These results had no significant difference with control group (saline 1 ml p.o.) about the extent of erosion. In histological study of the erosive region by scanning and light microscopy, we also found no differences in the depth of erosion between dmPGE2 group and control. In addition, dmPGE2 increased the gastric volume and mucus thickness significantly. These data suggest that following two effects by PGs play major role in cytoprotection of the gastric mucosa; (1) dilution of necrotizing agents by increased gastric content, and (2) thickening of the mucus gel layer. PMID- 2232297 TI - [An experimental study of the action of dopamine in suppressing pentagastrin stimulated gastric acid secretion and its mechanism in rats]. AB - The action of dopamine (DA, 10 micrograms/kg/min) on pentagastrin (16 micrograms/kg/hr) stimulated gastric acid secretion was studied by use of Ghosh Schild's rats. DA suppressed pentagastrin-stimulated gastric acid secretion 44.6 percent compared with the level before administration. This decrease in acid was inhibited by pretreatment with beta 1 and beta 1 + beta 2 blockers and pretreatment with DA1 + DA2 and DA1 antagonists. The gastric acid secretion with DA1 agonist decreased 36.4 percent from the level at the time of pentagastrin administration. This decrease was inhibited by pretreatment with beta 1 blocker, but suppression of gastric acid secretion by beta 1 + beta 2 stimulator was not inhibited by pretreatment with DA1 antagonist. These results suggest that DA stimulated beta 1 adrenalin receptor via DA1 receptor and thereby suppresses pentagastrin-stimulated gastric acid secretion. PMID- 2232299 TI - [Role of tissue kallikrein in chronic gastritis]. AB - Tissue kallikrein could be specifically demonstrated in the human gastric mucosa using sandwich-type enzyme-linked immunosorbent assay. Eighty-five patients with chronic gastritis were then studied to investigate the relationship of tissue kallikrein to endoscopic and pathologic findings. The endoscopic Congo red method was used to classify the atrophic pattern of each patients gastric mucosa into the normal, closed or open type. Tissue kallikrein increased significantly in the closed type compared with the normal type (P less than 0.01) and in the open type compared with the closed type (P less than 0.001). Pathological findings were classified into three groups: (A) normal surface epithelium, with slight infiltration by inflammatory cells; (B) atrophic surface epithelium, with marked infiltration by inflammatory cells; and (C) atrophic surface epithelium, with marked infiltration by inflammatory cells and intestinal metaplasia. Tissue kallikrein significantly increased in the B group compared with the A group (P less than 0.01) and in the C group compared with the B group (P less than 0.001). Tissue kallikrein markedly increased with the appearance of intestinal metaplasia in the open type rather than in the closed type. An immunohistological study demonstrated that tissue kallikrein was present in the cells showing intestinal metaplasia and goblet cells. These findings suggest that chronic gastritis is a process of reconstruction of gastric mucosa. PMID- 2232300 TI - [Role of PAF for the formation of gastric mucosal injury induced by ischemia reinfusion in the rat]. AB - Oxyradicals of neutrophils are supposed to play a role in the formation of gastric mucosal injury induced by ischemia-reinfusion (I-R). Recently, platelet activating factor (PAF) is suggested to be involved in the I-R injury as one of chemical mediators since this substance may be produced in hypoxic tissue, stimulating oxyradical generation of neutrophils. In the present study, using CV 3988, a PAF antagonist, the severity of gastric mucosal damage and chemiluminescence (CL) activity of neutrophils of circulating blood were measured to evaluate the role of PAF in the I-R injury. SD rats fasted overnight were anesthetized and instilled 0.1N HCl into the stomach. Rats were then subjected to reduction of blood pressure to 20-30 mmHg for 20 min by bleeding followed by reinfusion of shed blood for 20 min. Two groups of rats each received 10 mg/kg CV 3988 (PAF-A grup) or saline (I-R group) i.v. 5 min prior to bleeding. After killing rats, the area of gross gastric lesions and the index of histologic damage were assessed. In separate PAF-A and I-R groups of rats, and control rats received saline i.v. and no hypotension, blood samples were collected from the portal vein and the abdominal aorta 45 min after acid instillation. Luminol dependent CL stimulated by PMA of blood samples was measured using the photometer Monolight 401. CL activity was expressed as [peak CL/neutrophils number].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232301 TI - [Protease activities in gastric and colon cancer tissues]. AB - Activities of cathepsin B, cathepsin L, and plasminogen activators (urinary type plasminogen activator and tissue type plasminogen activator) were assayed in homogenates of cancer tissue, normal tissue closely surrounding the cancer tissue, and normal tissue distant from the cancer tissue from 30 patients undergoing surgery for gastric cancers and 10 patients undergoing surgery for colon cancers. Activities of those proteases were also assayed in homogenates of adenoma tissue from 10 patients undergoing polypectomy for colon polyps. In the gastric cancer tissue homogenates, the activities of cathepsin B, cathepsin L and tissue type plasminogen activator were significantly higher than in normal tissues. By contrast, the activities of urinary type plasminogen activator of gastric cancer tissues were significantly lower than normal tissues. In the colon cancer tissue homogenates, the activities of cathepsin, B, cathepsin L, and urinary type plasminogen activator were significantly higher than in normal tissues. On the other hand, the activities of tissue type plasminogen activator of cancer tissues were significantly lower than normal tissues. But there were no significant differences in the activities of plasminogen activators between the cancer tissues and adenoma tissues. These results suggest that cathepsin B and cathepsin L play an important role in gastric and colon cancer proliferation and evolution, although the roles of plasminogen activators in gastric and colon cancer proliferation and evolution and in the colon adenoma-carcinoma sequence are still unknown. PMID- 2232302 TI - [Endotoxemia and its compensatory mechanisms in experimental liver cirrhosis]. AB - This study was performed in order to elucidate the mechanisms of systemic endotoxemia in liver cirrhosis. For this purpose, the method of measuring biliary endotoxin was established. Endotoxin levels between in the bile and in the plasma in cirrhosis were compared using a modified method of chromogenic quantitative endotoxin assay in an attempt to clarify liver function of clearing portal endotoxin originated from the gut. And functional activities of the reticuloendothelial system were also examined by radioassay with 59Fe-labelled iron-chondroitin sulfate colloid and by enzymohistochemistry of acid phosphatase. Both the plasma and biliary endotoxin levels in liver cirrhosis were significantly higher, compared to those in control. The functional activities of the reticuloendothelial system, particularly of the Kupffer cells, were decreased in liver cirrhosis. These data provide evidence that in liver cirrhosis systemic endotoxemia is mainly due to a decrease of functional activities of Kupffer cells. On the other hand, the excretion of endotoxin into the bile is increased, compensating the decreased functional activities of Kupffer cells. This implies that the uptake of endotoxin and its excretion into the bile by hepatocytes might be one of the mechanisms of clearing excess endotoxin in the plasma in liver cirrhosis. This study also draws the importance of measurements of endotoxin levels in the bile in liver diseases. PMID- 2232303 TI - [A case of enterocolitis with diffuse multiple aphthoid lesions in which non caseous granulomas were demonstrated microscopically]. PMID- 2232304 TI - [A case of hepatitis A associated with thrombocytopenia, leukopenia and acute renal failure]. PMID- 2232305 TI - [A case of evaluation of hepatic hemangioma on phosphorus 31 magnetic resonance spectroscopy (31P-MRS)]. PMID- 2232306 TI - [A case of retroperitoneal schwannoma mimicking a cystadenoma of the pancreas]. PMID- 2232307 TI - [Osteoporosis--from the view point of the orthopedic surgeon]. AB - It is commonly accepted that the incidence of osteoporosis, as well as hypertension and diabetes, increases with age. With the expansion of the elderly portion of the population in society, the number of cases of osteoporosis and its related fractures must correspondingly increase. Regarding the effect of the level of decreased bone mass or bone mineral density of patients with vertebral body or hip fracture, the incidence rate of fractures significantly increases when the bone mass level of patients becomes less than -3 S.D. of the peak bone mass level at each of the respective sites. As a result, areas of under -3 S.D. area of te peak bone mass level are considered to be fracture risk area. When treating osteoporosis patients, special consideration must be given to other age related complications. One third of hip fracture patients already have dementia, hypertension, or cerebrovascular disorders at the time of injury. Exercise and weight bearing are important for the treatment and prevention of osteoporosis because of their positive influence on the muscles and the bone tissue of the patients. PMID- 2232308 TI - [Trends, risk factors, and prevention of ischemic heart disease in Japan]. AB - The mortality from ischemic heart disease has increased steadily in most industrialized countries from the 19th century up to 1970. In some developed countries, such as the U.S.A. and Australia, it started to decrease in the nineteen seventies and accelerated recently. However, it has increased in some East European countries, such as Rumania, Poland and Hungary. The mortality had been extraordinarily low and the age standardized rate declined since the nineteen seventies in our country as in the U.S.A. These finding strongly suggests the possibility of prevention of ischemic heart disease worldwide. Among the risk factors, hypertension has gradually decreased due to treatment and lower intake salt in Japan. However, the compliance of antihypertensive treatment could be improved and the average intake of salt further decreased. The frequency of hypercholesterolemia was quite low for many years, but increased recently in Japan. However, the national average level of serum cholesterol is probably close to 200 mg/dl, and the new cholesterol level data will be revealed by the national survey in 1990. The world-famous high figure of smoking among Japanese men has been declining for these 20 years down to 61.2% in 1988, along with an exceptionally low rate for women in industrialized countries. The average figure of body weight by stature was in line with the desirable body weight for Japanese and the average intake of lipids has leveled off recently according to the National Nutrition Survey. After all it can be concluded that incidence of ischemic heart disease could be reduced further, even in Japan. PMID- 2232309 TI - [Development of coronary atherosclerosis in the elderly]. AB - The role of aging, hypertension and plasma cholesterol in the development of coronary atherosclerosis was examined in 3569 consecutive autopsy cases, aged 60 to 99 years, at the Tokyo Metropolitan Geriatric Hospital. The prevalence of coronary atherosclerosis increased with aging. Both systolic and diastolic hypertension were related to the prevalence of coronary atherosclerosis. High plasma cholesterol (230 mg/dl) was related to increased prevalence of coronary atherosclerosis. This effect was observed in a hypertensive group, but not in a normotensive group. To define the effect of hypertension on vascular diseases, endothelial cells from spontaneously hypertensive rats (SHR) were obtained and characterized in terms of cellular response. Cellular Ca2+ level in response to A23187 was significantly enhanced in SHR compared to normotensive Wistar-Kyoto rats (WKY). Thus, aging, hypertension and high plasma cholesterol are risk factors for coronary artery atherosclerosis in the elderly. PMID- 2232310 TI - [Angiographic progression and regression of coronary atherosclerosis]. PMID- 2232311 TI - [Progression of coronary atherosclerosis and the non-invasive evaluation in older patients]. AB - To evaluate characteristics of coronary atherosclerosis in older patients and to elucidate the role of dipyridamole myocardial perfusion scintigraphy (DMPS) in the assessment of patients with coronary artery disease, 437 patients (330 men, 107 women, age range 13-85 years) initially underwent coronary angiography (CAG) and DMPS. Coronary risk factors were evaluated in relation to the severity and progression of coronary atherosclerosis. Cardiac events were also evaluated during the follow-up period of 39 +/- 19 months (range 1-77 months). Assessment of five coronary risk factors, including hypercholesterolemia, diabetes, hypertension, positive family history, and history of smoking, was made in 212 patients in relation to the severity of coronary atherosclerosis. In patients with insignificant lesions or single vessel disease, prevalence of hypercholesterolemia and positive family history was lower in older patients (65 years or older) than in younger patients (64 years or younger), but significant difference was not found in prevalence of diabetes, hypertension, and history of smoking. In patients with multivessel disease, there was no significant difference in prevalence of coronary risk factors between the two groups except history of smoking. Repeated CAG was performed in 27 patients during follow-up. Nineteen of them experienced increased symptoms of angina and eight patients newly developed acute myocardial infarction. The patients with increased angina had more risk factors, and majority of them (74%) showed some progression of previously noted severe stenoses in the proximal coronary arteries. In patients with new infarction, 62% of them showed new total occlusions as infarct-related lesions, although there were some patients who showed progression of previously noted severe lesions. DMPS was performed in 437 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232312 TI - [The effect of conventional therapy on coronary risk factors]. PMID- 2232313 TI - [Risk factors relating to coronary artery disease in the elderly]. AB - A total of 224 patients with coronary artery disease (CAD) and 167 healthy control beings (C) were evaluated for coronary risk factors. Analysis of low age subset (age less than 55) disclosed hypertension and hypercholesterolemia were more common findings in CAD compared with C. Significantly elevated plasma triglyceride (TG) and low density lipoprotein cholesterol (LDL-C), and reduced high density lipoprotein cholesterol (HDL-C) concentrations were found in CAD, accompanied by significant increase of atherogenic index (AI). In CAD, a decreased number of males and smokers was noted in high age subset (age over 65). Significantly reduced plasma TG and elevated HDL-C were observed in the elderly compared with the young. AI was also significantly higher in this group. Therefore, in CAD, the level of coronary risk factors seemed to be attenuated in the hig age subset compared with the low age group, which was different from the findings in C in whom significantly increased AI was noted in the elderly. In 61 CAD cases, lipid profiles were monitored for 5 years in average. Significant changes recognized during this period were the reduction of TG, LDL-C and AI along with the elevation of HDL-C, suggesting their risk to be improved. To examine the metabolic effects of diuretics, 52 patients with essential hypertension on trichlormethiazide for long periods were subjected to the substitution of this drug by the inhibitor of angiotensin converting enzyme, enalapril, for more than 3 months. At the end of each treatment, measurements of blood sugar (BS) and insulin (IRI) were made together with lipid analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232314 TI - [Prevention of progression of coronary atherosclerosis by drug and diet therapy]. AB - In 102 patients with ischemic heart disease the severity of stenosis was classified into 7 grades (0, 25, 50, 75, 90, 99, 100%) in accordance with the AHA reporting system. The coronary angiograms were compared at first and second catheterization (intervals 2-84 months) and progression was considered present if the stenosis in the second study showed more than one grade increase in comparison with the first study. Fifty six patients met criteria for progression. Risk factors were obtained within the first second catheterization. Drug and diet therapy were evaluated by interview. No significant difference could be found between the progression (P) group and the nonprogression (N) group in relation to family history and obesity. A history of hypertension was more common in the P group. In respect to blood sampling, the values of total cholesterol, Apo B, CII, E and Apo B/AI were significantly higher in the P group than those in the N group at first and second catheterization. The percentage of patients showing abnormal levels of blood sugar and lipid were higher in the P group than the N group although the percentage of patients with drug and diet therapy were higher in the P group than in the N group. The percentage of patients with diet therapy for hyperglycemia and hyperlipidemia were higher in the P group, however weight increase was more common in the P group. These data suggest that sufficient diet and drug therapy is necessary for patients with risk factors. PMID- 2232315 TI - [Hyperlipidemia impairs vascular endothelium-dependent relaxation in pig coronary arteries]. AB - We examined the effects of a low pathophysiological level of hyperlipidemia and atherogenic lipoprotein (LDL) on the vascular responsiveness of isolated pig coronary arteries. Firstly, we studied the change of vascular responsiveness after feeding a cholesterol-rich diet to pigs for 4 or 9 weeks. Serum cholesterol level in pigs fed with the cholesterol-rich diet reached 218.5 +/- 32.9 mg/dl compared with 85.5 +/- 8.4 mg/dl in controls. Segments of the arteries were mounted in organ chambers for isometric tension recording. Contraction caused by KCl or prostaglandin F2 alpha was not altered significantly by hypercholesterolemia. Relaxation in response to Ca2+ ionophore A23187 or nitroglycerin was not altered significantly by hypercholesterolemia. Relaxation in response to Ca2+ ionophore A23187 or nitroglycerin was not altered. Endothelium-dependent relaxation evoked by high but not low concentrations of bradykinin and substance P were reduced in pigs fed with the cholesterol-rich diet for 4 weeks as compared with those in normal pigs. Those evoked by bradykinin, substance P, and serotonin were significantly reduced in pigs fed with the cholesterol-rich diet for 9 weeks. Histologically, the fatty changes or intimal thickening were not so evident in coronary arteries of pigs fed for 4 weeks with the cholesterol-rich diet, but only minimal changes were observed in those fed with the diet for 9 weeks by light or electron microscopy. Secondly, the direct effects of LDL on the vascular responsiveness were examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232316 TI - [Some considerations on progression and regression of coronary arteriosclerosis based on histological studies of acute coronary thrombosis]. AB - This study showed that studies of structural changes of arteriosclerotic coronary lesion and coronary flow in the stenotic segments are very important for understanding the progression and regression of coronary sclerosis. In control groups of both sex over 50 years of age (544 males and 400 females), the frequency of stenosis of over 75% of 3 main coronary branches was approximately 20% in cases under 69 years of age and about 30% in cases over 70 years. In cases of myocardial infarction over 50 years of age (157 males and 89 females), stenosis of over 90% was approximately 90% in te left anterior descending artery, 70-80% in the right coronary artery and 70% in the left circumflex artery and three vessels showing stenosis over 90% were found in half of the cases. Of 70 coronary arterial lesions found in 67 cases of acute myocardial infarction, 48 were found in over 90% stenotic segments, 16 in over 75%, the rest in under 75%. Hemorrhage in atheroma was found in 55 lesions, atheroma or thick intima without hemorrhage in 9, calcified focus in 3 and coronary embolism in 3. Of 67 thrombi, 44 occlusive and 3 mural thrombi were found in over 90% stenotic segments, 13 and 2 in over 75% stenotic segments and 2 and one in segments and 2 and one in segments with under 75% stenosis, respectively. Histological findings of coronary thrombi showed that in 45 of 65 thrombi, two zones of differing age of thrombus could be identified and the rest were fresh thrombi.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232317 TI - [Left ventricular diastolic filling in elder patients with systemic hypertension]. AB - To study the significance of left ventricular (LV) diastolic filling in elder patients with hypertension (HT), cardiac blood pool imagings with Tc-99m were obtained at rest in 17 normal subjects and 28 patients with systemic hypertension. The patients with hypertension did not show any evidence of coronary heart disease, renal insufficiency or other disease. Moreover, they showed normal LV ejection fraction (LVEF) and normal LV wall motion. They were divided into 4 groups: 1) normal-young (less than 60 years old, n = 10), 2) normal-old (greater than or equal to 65 years old, n = 7), 3) HT-young (less than 60 years old, n = 15), 4) HT-old (greater than or equal to 65 years old, n = 13). From the LV volume curve and its first differentiation curve, LVEF, mean first third ejection rate (ERm) and peak ejection rate (PER) were obtained as indices of the LV systolic function, and LV diastolic filling rate during the first third of diastole (FRm) and peak filling rate (PFR) were obtained as indices of LV diastolic function. All indices of LV systolic function were similar in all groups. In contrast, LV diastolic indices (FRm and PFR) of older groups were significantly lower than those of young groups both in HT and normal. Also, LV diastolic indices in HT groups decreased significantly in comparison with normal groups of the same age group. Among diastolic indices, FRm could distinguish patients with HT from normal subjects of the same age group more accurately than PFR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232319 TI - [Localized callosal infarctions and dementia]. PMID- 2232318 TI - [An aged case of orthostatic hypotension possibly due to parasympathetic neurodysfunction]. AB - 94-year-old male patient, with orthostatic hypotension, possibly due to impairment of vasoconstriction and parasympathetic nervous system dysfunction was reported. This patient experienced faintness and lower muscle weakness on standing. The blood pressure was 180/90 mmHg in a supine position, while it significantly decreased to 100/58 mmHg in an upright position. There was no evidence indicating the presence of organic brain diseases, cardiovascular diseases, and endocrine diseases, plasma catecholamine, renin, aldosterone, and vasopressin levels at rest were within normal range. Thus, the cause of orthostatic hypotension of this patient was unknown. His systolic blood pressure decreased by 70 mmHg, and his diastolic blood pressure also decreased by 25 mmHg in response to a 70 degrees head-up tilting test (170/71-100/46 mmHg). Plasma vasopressin level significantly increased in response to this test (0.62-67.2 pg/ml). Plasma catecholamine levels also increased (Adr 0.01-0.10 ng/ml, Ndr 0.05 0.22 ng/ml). Other autonomic nervous system examinations revealed normal responses to mental arithmetic test, hyperventilation test, cold pressure test, and adrenalin test. However, the results of the carotid occlusion test, acetylcholine test, atropine test, phenylephrine test were considered to be abnormal. From these findings, we concluded that the functions of sympathetic nervous system were almost intact, while the parasympathetic functions were impared in this case. The orthostatic hypotension of the patient as effectively treated with fludrocortisone. This report suggests that impairment of vasoconstriction and parasympathetic neurodysfunction might be involved in the development of orthostatic hypotension in the elderly. PMID- 2232320 TI - [Assessment of physical activity by means of a calorie counter combined with an accelerometer]. AB - To establish an easy and convenient method for assessing the daily physical activity of workers, validity of a calorie counter combined with an accelerometer (KENZ Calorie Counter) was tested and compared with the method of daily survey and Stanford's interview method for energy consumption of daily physical activity. The subjects of this study were 92 volunteers. Energy expenditure of daily physical activity during 3-4 d was measured in 20 volunteers by means of a calorie counter, and the daily energy consumption was calculated from relative metabolic rates of physical activity. In the remaining 72 volunteers the energy consumption over 4-7 d was measured by means of a calorie counter and calculated from the Stanford's interview method. Correlation of the energy expenditure of daily physical activity measured by calorie counter (y) and that calculated from daily survey (x) was y = 0.74 x + 473 (r = 0.91, n = 56). Correlation of the calorie expenditure over 4-7 d measured by the calorie counter (y) and that predicted by Stanford's interview method (x) was high (y = 0.65 x + 3513, r = 0.86, n = 72). Relationship between the energy expenditure measured by the calorie counter (y) and that calculated by both daily survey and Stanford's interview method (x) showed a high correlation (y = 0.84 x + 518, r = 0.98, n = 128). These results suggest that a calorie counter combined with an accelerometer is valid for assessing the daily physical activity of workers. PMID- 2232321 TI - [Mental health in software engineers. II. Classification of occupational stressors, and relationship between occupational stressors and psychiatric disorders]. AB - Occupational stressors and psychiatric disorders were studied in a sample of 101 male software engineers. Psychiatric diagnosis was based on DSM-III (Diagnostic and Statistical Manual of Mental Disorders, Third Edition). The results can be summarized as follows: 1) More than 30% of the subjects were not satisfied with their work. 2) Occupational stressors ascertained in the interview could be classified into "quantity of job," "quality of job," "role in organization," "relations with others," "work conditions," "career development," "reward," "organizational structure and climate," "low social support," and "lack of decision making." "quality of job" (35%), "quantity of job" (30%), and "role in organization" (33%) were the most common stressors for the subjects. 3) Among the occupational stressors, only "quantity of job" was significantly related to psychiatric disorders (p less than 0.05). The results suggest that many software engineers are not satisfied with their work and that "quantity of job" has the greatest influence on their mental health. Some measures should be taken to avoid potential health hazards, for the research findings indicate a relationship between occupational stressors and mental health in software engineers. PMID- 2232322 TI - [Twenty years' follow-up study of asbestos workers]. AB - This report describes a cohort study conducted on workers who were employed in a factory mainly manufacturing asbestos yarn and cloth and were followed from 1964 to 1981. A total of 208 workers (73 males and 135 females) could be traced and 15 deaths were observed by the end of 1983. Among them, three had lung cancer and its relative risk was 6.8 (p less than 0.05) computed based on the age, sex and year specific death rates of Osaka Prefecture. One case of peritoneal mesothelioma was also found. The period from first asbestos exposure to death of these four cases of asbestos-related malignancies was more than 25 yr. In the analysis of the employees who had more than 1 yr of exposure to asbestos and those who had already been engaged in this factory at the beginning of the observation, the relative risk of lung cancer was 8.1 and 13.6, respectively. PMID- 2232323 TI - [Disturbance of acid-base balance in cadmium-induced renal tubular dysfunction]. PMID- 2232324 TI - [Determination of cadmium, cobalt, copper, nickel and lead in urine by inductively coupled argon plasma emission spectrometry after solvent extraction]. PMID- 2232325 TI - [Prognosis of cadmium-induced renal dysfunction after reduction of exposure]. PMID- 2232326 TI - [Nondestructive X-ray fluorescence spectroscopic imaging of trace elements on methylmercury and selenium administered guinea pigs]. PMID- 2232327 TI - [Effects of soft drink intake on the concentration of urinary hippuric acid in workers exposed to toluene]. PMID- 2232328 TI - ABO blood-typing of bloodstains by dot-ELISA method. AB - The ABH antigens of bloodstains which were effectively solubilized in phosphate buffered saline by crushing in a mortar were detected on a nitrocellulose membrane by enzyme-linked immunosorbent assay (ELISA). The analyses for characterization showed that the extracted substances consisted of various components of the red cell with molecular weights of more than 30,000. ABO types of some aged bloodstains were determined by this simple procedure. This method is a useful tool for determining various blood-groups from bloodstain. PMID- 2232329 TI - The movement of blood formaldehyde in methanol intoxication. II. The movement of blood formaldehyde and its metabolism in the rabbit. AB - The movement of blood formaldehyde in rabbits that were intoxicated with methanol has been investigated by simple headspace gas chromatography-mass spectrometry for the microdetermination of formaldehyde in the blood. When methanol alone was administered to rabbits orally, formaldehyde could not be detected in the blood. Further, in an experiment on the metabolism of methanol in vitro, formaldehyde was not detected in specimen samples but formate was. In contrast, when methanol was orally administered to rabbits that had been pretreated with diethyldithiocarbamate (DDC), an aldehyde dehydrogenase (ALDH) inhibitor, 17 to 33 microM of formaldehyde were detected in the blood 4 hours later. However, formaldehyde was not detected in the blood when methanol was orally administered to rabbits that had been pretreated with pyrazole, an alcohol dehydrogenase (ADH) inhibitor. After rabbits were given an intravenous administration of formaldehyde, and on the addition of formaldehyde to a rabbit liver homogenate and blood, the formaldehyde in both instances was metabolized rapidly. Formaldehyde that was not metabolized within 10 to 15 minutes, however, bound to the tissue proteins. Therefore, according to the results of this study, formaldehyde was seen to be rapidly metabolized to formate without accumulating in the blood or binding to the tissue proteins. Formaldehyde thus appears to have little influence on the symptoms of methanol poisoning. PMID- 2232331 TI - Studies on asphyxia; on the changes of the alveolar walls of rats in the hypoxic state. III. The hypoxic state by carbon monoxide gas. AB - Experimental studies on asphyxia due to the hypoxic state produced by carbon monoxide gas were achieved. The morphological changes such as 1) faint pinkish homogeneous substance in the alveoli by H&E staining, 2) debris-like structure of medium electron dense substance on the surface of alveoli and/or full-filling the space of alveoli which were almost the same as observed in our previous reports except the appearance of a plenty of fibrin fibers in the debris-like structure and in part the close connection with myelin configurations as well. PMID- 2232330 TI - Blood group antigens transformed by proteinase K-treatment and the discovery of a natural autoantibody of these treated red blood cells. AB - Proteinase K-treatment of red blood cells either diminished or abolished the antigenic activities of glycophorin A and glycophorin B, and revealed the presence of a cryptic antigen that was recognized by antibody naturally existing in the autoplasma. About ninety five percent of all healthy persons have this autoantibody belonging to the IgM classification, whose titer ranges from 2 to 32. The activity of this autoantibody was absorbed by histidine and glutaminic acid. We were able to isolate this autoantibody from the plasma by means of an alkaline elution method and the autoantibody did not agglutinate chymotrypsin treated red blood cells and red blood cells treated with chymotrypsin, following proteinase K-treatment. These results indicate that after proteinase K-treatment this autoantibody may not have an affinity for glycolipids, but for proteins digested by chymotrypsin. PMID- 2232332 TI - Demonstration of ingested thinner. AB - Taking a practical forensic case that provided an opportunity, an attempt was made to prove that paint thinner had been ingested by the victim. One ml of standard thinner solution, which was prepared by mixing toluene, ethyl acetate, and isobutanol, was given by gavage to rats, after which, on sacrifice of the animals, the distribution of thinner components in the body tissue and in the gastric contents was examined by gas chromatography, using the salting-out technique and the headspace method. Three thinner components and ethanol, a metabolite of ethyl acetate, were found to be present in the gastric contents, whereas only toluene was found in the blood and in the other tissue. From these results we thus have concluded that paint thinner taken can be proved by detecting the presence of ethyl acetate and isobutanol together with toluene in the stomach, whereas only toluene can be detected in the body fluids and the other tissue. PMID- 2232333 TI - Characterization of a monoclonal crossreacting anti-A, B antibody. AB - Ten monoclonal antibodies (MAbs) have been produced from mouse-mouse hybridomas raised to dispase-treated human group AB red blood cells (RBCs). One of these antibodies, T-1435A, reacted with the RBCs of the human group A, B, and AB, but not to the RBCs of group O. The reactivity of T-1435A was specific to a single anti-A, B but not to a mixture of an anti-A and an anti-B. Also, T-1435A reacted strongly with protease- and neuraminidase-treated RBCs, and the susceptibility of its corresponding antigen was markedly reduced by alpha-galactosidase treatment. T-1435A agglutinated group A RBCs from chimpanzees, and its reactivity to RBCs was recognized in tamarins and in owl monkeys. However, this antibody demonstrated a stronger affinity for human RBCs. Further, using A- or B transferase, human and chimpanzee RBCs that transferred from group O to A or to B were agglutinated by T-1435A. Finally, the corresponding antigen appears to have a structural determinant that fits the T-1435A combining site. Therefore, this monoclonal antibody is useful for determining the ABO blood-grouping when used as a conventional reagent that segregates group O RBCs from the RBCs of the other groups. PMID- 2232334 TI - [Locomotor activity and urinary excretion of orthocresol in rats exposed to toluene]. AB - To clarify the effect of toluene on behavior, and to evaluate urinary orthocresol excretion as an indicator of toluene exposure and locomotor activity, we have investigated the urinary orthocresol excretion and levels of locomotor activity in rats exposed to 0-3000 ppm of toluene intermittently for 2 hours. The levels of locomotor activity were measured by a laboratory animal activity measuring apparatus (ANIMEX-III). Exposure of adult male rats to more than 1000 ppm (v/v) of toluene caused an elevation of the urinary orthocresol excretion and a good correlation was noted between the amount of toluene in the air and the urinary orthocresol excretion. Exposure to over 2000 ppm of toluene suppressed the level of locomotor activity, and there was a good correlation between the level of locomotor activity and the urinary orthocresol excretion. Further, rats exposed to 3000 ppm toluene showed elevated levels of locomotor activity during a 10-hour period after exposure. These patterns of urinary orthocresol excretion and the levels of locomotor activity remained unchanged even when rats were exposed to 3000 ppm of toluene intermittently over a 4-day period. PMID- 2232335 TI - [Sudden death of alcohol withdrawal syndrome--report of a case]. AB - A 50-year-old driver was arrested in a drunken stupor while he was driving a track. He suddenly died after five days of the arrest in a jail. As time went by, various symptoms of alcohol withdrawal appeared. He was in the state of delirium treatments for about a day before he died. Gross and microscopical examination revealed fibrosis and fatty degeneration of liver and heart lesions representing chronic and acute ischemia. We discussed the cause and the mechanism of the death in the case and reviewed those in the previous observations. PMID- 2232336 TI - [Calculation of carbon monoxide concentration based on a ventilation model for two rooms]. AB - We have estimated the gas concentration in an upstairs room following leakage of gas from a ground-floor room. The method used to calculate the gas concentration in the upstairs room was based on a ventilation model for two rooms. The assumptions on which the calculation was based were: 1) Uniform diffusion of gas. 2) Presence of slight openings in the room wall. 3) Reported data on the volume of the openings between the downstairs ceiling and the upstairs floor. 4) Calculation of the ventilation rate based on buoyant force. The upstairs gas concentration became steady within 4-7 h after the leakage. The ventilation rates for the 1st and 2nd floors at a steady state were 0.86 and 0.63 (room volume/h), respectively. The volume of the room did not affect the gas concentration at the steady state. PMID- 2232337 TI - [Detection of restenosis after successful percutaneous transluminal coronary angioplasty (PTCA)--usefulness of exercise thallium scintigraphy]. AB - We studied the efficacy of stress thallium scan in detecting restenosis after primary successful PTCA. There were 21 patients with angina pectoris and 16 patients with previous myocardial infarction. The sensitivity and the specificity of stress thallium scan in detecting restenosis were superior to those of stress electrocardiography or chest pain complained in follow-up period. In multi-vessel disease, we could assess the vessel developing restenosis more easily than stress electrocardiography. Initial thallium %UPTAKE RATIO was significantly improved after PTCA but redecreased in patients developing restenosis. In patients showing residual redistribution despite of not developing restenosis, we could judge vessel patency by gradually improving initial %UPTAKE RATIO after PTCA. Thus, stress thallium scan proved to be useful in detecting restenosis after PTCA. PMID- 2232338 TI - [Serial change of 123I-metaiodobenzylguanidine (MIBG) myocardial concentration in patients with dilated cardiomyopathy]. AB - 123I-Metaiodobenzylguanidine (MIBG) is expected to be useful agent for functional evaluation of the myocardial sympathetic innervation. The aim of this paper is to investigate serial change of 123I-MIBG myocardial concentration in patients (pts) with dilated cardiomyopathy (DCM) as compared with 201Tl uptake. Eight pts with DCM and six non-cardiac subjects (controls) were examined. After injection of 111 MBq (3mCi) 201Tl and 111 MBq (3 mCi) 123I-MIBG, simultaneous myocardial imaging in anterior view was performed for both tracers in every 30-60 minutes during 5 hours (6 images). Myocardial uptake ratio per pixel to the injected dose was calculated for each tracer with background and cross-talk correction on each image. In pts with DCM, myocardial uptake ratio of 123I-MIBG did not differ significantly from that of controls. The washout of 123I-MIBG from the myocardium, however, was significantly increased in pts with DCM as compared with controls. The % decrease of the radioactivity in 3 hours was 46.9 +/- 13.8% in DCM, whereas 18.0 +/- 7.7% in controls (p less than 0.05). Especially, the decrease in the early phase (less than 1 hour) was significantly larger in DCM than controls (21.2 +/- 7.5% vs 5.3 +/- 4.0%, p less than 0.01). For 201Tl, on the other hand, neither uptake ratio nor washout rate, differed significantly between the two. In conclusion, the rapid washout of 123I-MIBG in the early phase may reflect some sympathetic dysfunction in pts with DCM. PMID- 2232339 TI - [Serial assessment of denervated but viable myocardium following acute myocardial infarction by using 123I-MIBG and 201TlCl myocardial SPECT]. AB - 123I-MIBG is taken up by sympathetic nerve ending and provides a scintigraphic image of myocardial sympathetic innervation. We investigated the scintigraphic detection of denervated but viable myocardium following acute myocardial infarction by serial 123I-MIBG and 201TlCl myocardial SPECT. Fourteen patients were studied at acute (10 +/- 2 days) and chronic stage (86 +/- 10 days). Simultaneous dual SPECT was carried out after IV administration of 111 MBq (3 mCi) of 201TlCl and 123I-MIBG. The defect size of 123I-MIBG and 201TlCl were compared visually by using Bull's eye display generated from each myocardial SPECT. In all patients, 123I-MIBG defect showed larger compared to 201T1Cl defect at acute stage, which suggest the existence of denervated but viable myocardium. Of these patients, seven showed significant improvement of both defects, though 123I-MIBG defect showed slightly larger compared to 201TlCl defect, even at chronic stage. These patients had exercise induced thallium transient defect at infarcted area. The remaining 7 patients had no improvement of both defects at chronic stage, which suggest the complete scar at infarcted area. In addition to above study, 4 patients of old myocardial infarction demonstrated larger 123I MIBG defect compared to 201TlCl defect even at old stage, which thought to be pathogenesis of ventricular tachycardia. In conclusion, 123I-MIBG could evaluate sympathetic denervation and reinnervation noninvasively in the patients with acute myocardial infarction. PMID- 2232340 TI - [123I-IMP accumulation in the lung with bronchial asthma--early uptake and delayed washout]. AB - 123I-IMP is taken up by the pulmonary capillary endothelial cells during the first pass through the lung, and is slowly released from them. To look up the factors which influence on the prolonged 123I-IMP retention in the diseased lung, we examined the correlation between the 123I-IMP uptake during the first pass and the 123I-IMP retention. Patients with bronchial asthma had no abnormal finding in the chest X-ray photograph. However 123I-IMP release from their lungs was delayed. Some patients show a tendency that 123I-IMP uptake during the first pass was uneven, which suggested the change in amine uptake function of endothelial cells. However their correlation coefficients between the uptake during the first pass and the prolonged retention were very small. It was considered that the prolonged 123I-IMP retention in the diseased lung was not explained only by the change in uptake function of pulmonary capillary endothelial cell. PMID- 2232341 TI - [Myocardial adrenergic derangement due to myocardial ischemia: decreased myocardial uptake of I-123 metaiodobenzylguanidine after PTCA in a patient with effort angina]. AB - Regional denervation of adrenergic nerves has been clinically demonstrated in patients with myocardial infarction using I-123 metaiodobenzylguanidine (MIBG) scintigraphy. However, it is not clarified whether adrenergic denervation can be induced by prolonged myocardial ischemia as well as by myocardial infarction. This case with effort angina had 99% stenosis of right coronary artery and showed perfusion defects at inferior myocardial regions in the exercise thallium-201 study. However, inferior wall motion estimated by echocardiography and left ventriculography was normal indicating the absence of myocardial infarction. After percutaneous transluminal coronary angioplasty for the stenosis, I-123 metaiodobenzylguanidine (MIBG) and thallium-201 (Tl-201) myocardial scintigraphies were done to estimate the therapeutic effect of PTCA. Although the Tl-201 study during exercise showed normal findings indicating the success of PTCA, marked defects was detected at inferior myocardial regions in the I-123 MIBG studies just after and 4 hours after an intravenous injection of I-123 MIBG. These results suggest that adrenergic derangement may be induced by prolonged myocardial ischemia and may persist for periods even though myocardial perfusion is normalized. PMID- 2232343 TI - [A case of subacute cerebral infarction demonstrating hyperemia and crossed cerebellar diaschisis in I-123 IMP SPECT]. AB - SPECT with N-isopropyl-p-[I-123]iodoamphetamine were performed in a 81-year-old man with cerebral infarction. In the subacute phase, the radioactivity was increased in the infarct area where fogging effect and remarkable contrast enhancement was demonstrated in X-ray CT. The contralateral cerebellar hemisphere showed reduced activity due to crossed cerebellar diaschisis (CCD). In the chronic phase, the decrement of the activity in the infarct was observed. Increased activity in the subacute phase was thought to reflect the hyperemia in the infarct, while CCD suggested the decreased metabolic activity in the lesion. The coexistence of the hyperemia and the CCD indicates flow and metabolic uncoupling, which means "luxury perfusion". This case was also thought to demonstrate atypical findings of CCD in SPECT imaging. PMID- 2232342 TI - [A case of Hurthle cell carcinoma in the superior mediastinum]. AB - This is a report for an unusual case of oxyphilic cell adenocarcinoma originating from anterior mediastinum in a 36-year-old male who complained of his neck lymphoadenopathy. 201Tl whole body scanning showed increased uptake of the left supraclavicular and upper mediastinal regions. There was no history of prior operation nor irradiation to the thyroid or neck region. Chest CT scanning also demonstrated the tumor in the superior mediastinum, but the mass has no increased 67Ga uptake. No tumor in the thyroid lobes was apparent on thyroid scintiscanning, ultrasonography and neck CT. The mediastinal tumor resection, the right and left thyroid lobectomy and the neck lymphonodectomy were completed. Serial sectioning of the resected thyroid lobes failed to show any tumorous tissue. The light microscopic features of a Hurthle-cell tumor arising in the mediastinal ectopic thyroid and diagnosed by neck lymph node biopsy were presented. The tumor was clinically malignant, having metastasized to the bone and the neck lymph nodes. Non surgical treatment including radioactive iodine (131I) therapy and combination chemotherapy were disappointing. The patient deteriorated progressively and died 16 months after thyroidectomy. We describe here an unusual case of a papillary growing and thyroglobulin producing tumor in the superior mediastinal region without evidence of a primary thyroid gland tumor. PMID- 2232344 TI - [Thallium-201 thyroid scintigraphy of thyroid nodules--washout pattern of Tl-201 in thyroid nodules]. PMID- 2232345 TI - [Clinical trial of 111In-antimyosin antibody imaging: (5). Follow-up study and its safety]. PMID- 2232346 TI - [Basic and clinical studies of measurement of serum neopterin concentrations utilizing radioimmunoassay]. PMID- 2232347 TI - [Studies on radioimmunoassay kit for measuring urinary neopterin]. PMID- 2232348 TI - [Correction of time resolution of an ambulatory cardiac monitor (VEST)--using a pulsate cardiac phantom]. AB - Using ambulatory cardiac monitor (VEST) at exercise study, its time resolution is very important factor. We evaluated the time resolution of VEST using pulsate cardiac balloon phantom. Four analyses were carried out; no smoothing (NS) method, 3 points smoothing (3S) method, short sampling interval (SS) method, and digital filter (DF) method. By comparison of [delta EF[ ([EF: HR120-EF: HR60[) among 4 analysis methods, [delta EF[ by DF method was significant small. (NS: 3.58 +/- 3.01, 3S: 4.46 +/- 0.95, SS: 3.35 +/- 3.26, DF: 1.11 +/- 1.28%). We conclude that correction of time resolution by digital filter is necessary when we use VEST during exercise. PMID- 2232349 TI - [The development of a highly sensitive IgE immunoradiometric assay using monoclonal antibodies]. AB - We have developed two-site immunoradiometric assay (IRMA) for quantitation of human serum IgE, using two different anti-IgE monoclonal antibodies which recognize different epitopes on IgE molecule. We obtained 25 different monoclonal antibodies classified seven groups, and then two different monoclonal antibodies were selected for bead coater and tracer after checking the titer and specificity of each antibody. IgE IRMA we developed here showed good performance in terms of specificity, sensitivity and reproducibility. No cross-reactivity to IgG, IgM and albumin in the level of normal range was observed. The sensitivity for IgE assay was 0.6 x 10(-3) IU/tube and measurable range was 0.01-20.0 IU/tube (0.5-10(3) IU/ml). Coefficient of variations of Intra assay were 2.2-4.3% and average recovery yield was 92.5-108%. Good correlations with Phadebas IgE PRIST and Pharmacia IgE RIA were obtained i.e., y = 1.12x-0.19 (r = 0.96) and y = 0.97x-5.9 (r = 9.7), respectively. These results indicate that the assay system will contribute much to the routine diagnosis for atopic allergy disease and parasitic infections. PMID- 2232350 TI - [Assessment of ischemic damage of the cardiac sympathetic nerve function by semiquantitative analysis of 123I-MIBG (metaiodobenzylguanidine)-SPECT- comparison with 201Tl-Cl-SPECT]. AB - Recently 123I-MIBG scintigraphy has been developed for evaluating the function of cardiac sympathetic nerve. To assess its ischemic damage, dual SPECT with 123I MIBG and 201Tl-Cl were performed in 24 patients with ischemic heart disease and 8 normal subjects. In order to evaluate extent and severity of ischemic damage, Tl and MIBG abnormal scores were calculated by Bull's eye map. In patients with Non Q wave myocardial infarction (NQMI), MIBG abnormal scores were significantly higher than Tl scores (p less than 0.01). In the regions where regional wall motion showed hypokinesis, MIBG abnormalities were detected in all cases whereas Tl abnormalities existed only in 42%. MIBG abnormality score in NQMI group with negative T wave and wall motion asynergy was significantly higher than that of NQMI group without T wave abnormality and asynergy (p less than 0.01). Ischemic damage of cardiac sympathetic nerve seemed to contribute to negative T wave and stunned myocardium. 123I-MIBG scintigraphy was thought to be a sensitive and useful method for clinical evaluation of ischemic heart disease. PMID- 2232351 TI - [99mTc-MDP abnormal uptake in the femur shaft in hemi-lateral hip joint disorders]. AB - During the past 4 years, three-phase bone scintigraphy using 99mTc-MDP has been studied in 68 patients suffering from hemi-lateral hip-joint disorders. We were impressed on abnormal uptake of the shaft of femur on the involved side. 99mTc MDP uptake in the shaft of femur is compared with between involved leg and normal leg of 68 cases with hemi-lateral hip-joint disorders (76 examinations). We excluded cases of osteomyelitis, cases of malignant tumor, and post-operative cases. In early images, the 99mTc-MDP uptake is not always increased in involved side. But in delayed images, there are no patients whose normal side's 99mTc-MDP uptake is increased. The 99mTc-MDP uptake in early image is not related only with blood flow of the thigh but with the amount of soft tissue of the thigh. And the 99mTc-MDP uptake in delayed image is related with disuse osteoporosis. PMID- 2232352 TI - [Usefulness of ventilation and perfusion scans in patients with collagen-vascular diseases]. AB - We studied 32 patients with collagen-vascular diseases with Xe-133 ventilation scans (V) and Tc-99m MAA perfusion scans (Q). Five patients underwent sequential studies at intervals of more than 3 months. Mean transit time (MTT) was calculated from the Xe-133 wash-out curve. V, Q images and MTT were compared with chest X-ray films and the values of %DLco. Of 32 patients, 17 had no abnormal finding on the chest X-ray films. Of the 17 patients, however, V and/or Q abnormalities were found in 10 (59%), 14 patients (82%), respectively. Every patient with abnormal findings on the chest X-ray film showed both V and Q abnormalities. Overall, Q abnormality was more frequent and severer than V one. Of the 5 patients with the sequential studies, 3 showed prolongation of MTT in concordance with deterioration of pulmonary fibrosis. V and Q abnormalities were not necessarily relevant to %DLco. In conclusion, ventilation and perfusion studies are useful in assessing the regional pulmonary function in patients with collagen-vascular diseases. PMID- 2232353 TI - [Left ventricular ejection fraction derived from resting 201Tl myocardial images]. AB - To determine if resting 201Tl myocardial scintigraphy (rest-Tl) provides the information on left ventricular function, we compared preliminarily the parameters derived from rest-Tl with left ventricular ejection fraction (LVEF) derived from left ventriculography; while the parameters included Extent Score (ES), Severity Score (SS), Percent Uptake (PU), Area Index (AI). AI was derived from the averaging of [(A/B) x 100] in three or four central slices of short axis view on single photon emission computed tomography (A; area surrounded by inner edge of 201Tl myocardial image, B; area surrounded by outer edge of 201Tl myocardial image). The patients were comprised of 38 males and 16 females with a mean age of 53 years old (range 15-70) and classified into two groups; patients with myocardial infarction (n = 28, Group I), and patients with miscellaneous disease but without myocardial infarction (n = 26, Group II). In Group I, ES, SS and AI correlated with LVEF. If ES was less than 0.30, SS was less than 26.2, or AI was less than 19.8, LVEF was suggested more than 60% with an accuracy of 92%, 85% and 85%, respectively. In Group II, these did not correlate with LVEF. If there were area with PU less than 70% in the region perfused by left anterior descending artery or left circumflex artery, LVEF was less than 60% with an accuracy of 78%. In conclusion, rest-Tl images provide some informations on left ventricular function in some patients. PMID- 2232354 TI - [Platelet production, clearance and distribution in patients with idiopathic thrombocytopenic purpura]. AB - We have studied 8 normal subjects, and 12 patients with idiopathic thrombocytopenic purpura whose platelet counts ranged from 9 x 10(9)/L to 40 x 10(9)/L. Autologous platelets labeled with 111Intropolone were used for evaluation of mean platelet survival, platelet turnover, platelet sequestration sites, and platelet production (turnover) to clearance (sum of platelet uptake in the liver and the spleen) ratio. Platelet survival correlated directly with platelet counts. There was no significant correlation between the platelet sequestration pattern and platelet count, survival, or turnover. Sum of platelet uptake in the liver and the spleen showed a significant inverse correlation with platelet survival. No significant correlation was found between platelet turnover and platelet count. There was a significant correlation between the platelet production to clearance index when all subjects were analyzed. The distribution of platelet turnover showed considerable individual variation; eight of twelve patients showed platelet turnover less than mean minus 2SD of the control value, but others showed normal range. We conclude that although platelet destruction mechanism in RES shows a primary role of thrombocytopenia, impaired rate of effective thrombopoiesis may also contribute to disease severity in ITP. PMID- 2232355 TI - [123I-iodoamphetamine single photon emission computed tomography in three patients with amyotrophic lateral sclerosis]. AB - We examined the 123I-iodoamphetamine SPECT for 3 patients with ALS, who were clinically diagnosed. Patient 1 was a 31-years-old man, who had bilateral muscle weakness of his upper extremities, and spasticity in lower extremities. Patient 2 was a 51-years-old woman, who had marked weakness of her upper extremities and bulbar sign. Patient 3 was a 68-years-old man, who had severe degree of marked weakness of his upper extremities and mild bulbar signs. Cerebral cognitive function were all normal in three patients. Computed tomographic and magnetic resonance imagings showed moderate degree of cortical atrophy in patient 1, but no abnormalities in patients 2 and 3. In 123I-IMP SPECT, however, hypoperfusion were recognized on the bilateral fronto-parietal border zone areas in these three patients with ALS. It was suggested that patients with ALS showed varying degrees of impaired perfusion in the fronto-parietal border zone areas in spite of normal cognitive functions. PMID- 2232356 TI - [A case of pulmonary embolism diagnosed by 111In labeled platelet scintigraphy]. AB - Although the role of 111In platelet scintigraphy is established in the diagnosis of deep vein thrombosis, its indication in pulmonary embolism remains uncertain. We performed platelet scintigraphy in a patient with recurrent pulmonary thromboembolism, which revealed abnormal accumulation in the left hilar region. Pulmonary perfusion scintigraphy performed at the same time did not show perfusion defect. However, pulmonary angiography and thromboembolectomy demonstrated recurrent embolus in the hilus. This suggested that platelet aggregation in the left hilus shown by platelet scintigraphy was indeed related with recurrence of pulmonary embolism, and platelet scintigraphy is useful in detecting new development of thrombus in patient with recurrent pulmonary thromboembolism. PMID- 2232357 TI - [Diagnostic value of the transesophageal atrial pacing stress for Tl-201 myocardial SPECT]. AB - The stress study for Tl-201 myocardial SPECT (single photon emission computed tomography) of a patient with old myocardial infarction, who had occasionally felt a chest pain for the last 8 months was performed with the transesophageal atrial pacing. The examination was fastly started and regular pacing rates were completely obtained for every pacing rate (50-100/min). In spite of a little amount of the pacing stress, the finding of stress induced ischemia and MI were obtained on this patient. This result suggests that the transesophageal atrial pacing stress might be useful for the evaluation of ischemic heart disease by Tl 201 myocardial SPECT, and is easily applied to the old and the patient with disorder of leg movement. PMID- 2232358 TI - [Preparation and assessment of an animal model of Alzheimer's disease]. PMID- 2232359 TI - [Basic and clinical studies on radioimmunoassay of pancreatic phospholipase A2 (PLA2) (Part I)]. PMID- 2232360 TI - A historical pulmonary perspective. PMID- 2232361 TI - Dissociation of serum fructosamine from fasting plasma glucose or hemoglobin A1c in diabetics. AB - To evaluate serum fructosamine as an indicator for diabetic control, serum fructosamine (FRA), glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) were simultaneously measured in 452 diabetics in stable diabetic control. We divided the measured FRA according to the degree of deviation from the expected FRA into three types, hyper-FRA, normo-FRA and hypo-FRA. In the hypo-FRA to HbA1c group, frequencies of male (70 vs 35, 43%) and of nephropathy (61 vs 30, 18%) were higher and mean total serum protein (6.5 vs 7.4, 7.4 g/dl) and albumin (3.4 vs 4.1, 4.0 g/dl) were lower than those in the other two corresponding groups. Correlation was also poorer in the insulin-treated group than the others. These results probably reflect conditions of diabetic control and complication, and protein metabolism. Similar tendencies were observed in case of FPG. Therefore, the discrepancy of FRA gives a clue to detect poor control and complications of diabetes. PMID- 2232362 TI - Cellular immunity in myasthenia gravis after thymectomy and corticosteroid therapy. AB - Clinical and immunological changes in patients with myasthenia gravis (MG) who had extended thymectomy (Tx) and/or corticosteroid therapy were examined to elucidate the mechanisms of improvement following the treatments. The changes found were: 1) After Tx and steroid therapy, in patients with MG who showed clinical improvement, the CD4/CD8 ratio and B lymphocyte subpopulations were markedly decreased. 2) Linear correlations between two T-cell subsets were evident in CD3 against CD4 and CD4/CD8 against CD4 after both Tx and steroid therapy. 3) T lymphocytes-CD8 decreased immediately after Tx and returned to pre treatment levels within three weeks. 4) Cellular sensitization against a nicotine acetylcholine receptor (AChR)-like protein isolated from fetal calf thymus decreased after steroid therapy. These results indicate that clinical improvement in MG after the treatments was accompanied by a decrease in helper/inducer T lymphocytes, B lymphocytes and specific lymphocyte sensitization against nicotinic AChR. PMID- 2232364 TI - Pulmonary drug-metabolizing enzyme in alveolar macrophages in relation to cigarette smoking. AB - We measured the aryl hydrocarbon hydroxylase (AHH) activity in alveolar macrophages (AMs) and the AHH inducibility in peripheral blood lymphocytes (PBLs) of 56 subjects with and without lung cancer. There were no differences in the AHH inducibility in PBLs whether or not the host had lung cancer, regardless of a smoking history. The AHH activity in AMs in the current smoker group was significantly higher than in the non-smoker group. The AHH activity in AMs in the lung cancer group was higher than that in the non-lung cancer group, and the central-type group was significantly higher than the peripheral-type group. These results suggest that the AHH activity in AMs is associated with the development of lung cancer and a history of cigarette smoking. PMID- 2232363 TI - A survey regarding the disclosure of the diagnosis of cancer in Toyama Prefecture, Japan. AB - A survey regarding the revelation of the diagnosis of cancer to patients was conducted on 116 medical doctors (MD), 206 paramedical personnel (PP) and 789 lay persons (LP) in June 1989 in Toyama prefecture, Japan. When asked in the case that their parents or spouse had cancer, only 29.8% of all respondents answered that they would reveal the diagnosis of cancer to their family member. On the contrary, if they themselves had cancer, 56.3% of all respondents answered that they wished the diagnosis to be revealed, and 77.4% of these answered that they wished to be informed of the cancer diagnosis by the doctor in charge. They wanted to know the details of their condition from their medical doctor, and thought that they could receive this knowledge calmly. Thirty-one percent (34/108) of the doctors questioned reveal the diagnosis of cancer to their patients and 79.4% of these answered that they felt that telling the true diagnosis was good. A serious responsibility for the medical doctor was indicated. PMID- 2232365 TI - A family case of pyruvate kinase variant, PK 'Nichinan'. AB - A case of congenital hemolytic anemia caused by pyruvate kinase (PK) deficiency variant designated PK 'Nichinan' is presented. A 29-old patient with a history of anemia and hepatosplenomegaly had an episode of aplastic crisis associated with fever, abdominal symptoms and worsening hepatosplenomegaly. Study of the family members revealed that his mother and two of three siblings showed decreased PK activity whereas his father showed normal PK activity with a normal level of glycolytic intermediates. The patient was assumed to be a double heterozygote with two separate mutant genes from the parents despite the apparent normality of his father's erythrocyte PK. PMID- 2232366 TI - Pressor and hormonal responses to intravenous injection of metoclopramide in normotensive and hypertensive patients. AB - To assess the dopaminergic regulation of blood pressure and the renin-angiotensin aldosterone system in fourteen essential hypertension (EHT) and six normotensives (NT), intravenous injections of 10 mg of the dopamine antagonist, metoclopramide (MCP), were given. Essential hypertension patients were divided into two subgroups according to the basal values of plasma renin activity (PRA). Plasma prolactin (PRL), aldosterone (ALDO), norepinephrine (NE) and epinephrine (E) in seven high-renin EHT revealed significantly higher basal values than normal- and low-renin EHT. Intravenous injections of MCP caused significant increases in PRL and ALDO but not in NE, E and PRA in all subjects. However, in high-renin EHT the responses of PRL and ALDO were significantly marked compared to other subjects. In spite of these hormonal changes after MCP, blood pressure was unaltered. The present data suggest that "tonic inhibition" of PRL and ALDO by the dopaminergic system is partially regulated by the renin-angiotensin system regardless of the levels of blood pressure. PMID- 2232367 TI - Amyloidosis (AA type) with gastrointestinal involvement: resolution of gastric amyloid deposition in parallel with disappearance of the serum component of amyloid A protein. AB - The prognosis for secondary amyloidosis is better than that for the primary form. With arrest of the triggering disease, clinical improvement can be expected. Dramatic resolution of amyloid deposits, as proven by repeated biopsies, has been reported. We report on the effectiveness of amputation of the left thigh with chronic osteomyelitis in a patient with AA amyloidosis presenting with extensive amyloid involvement of the gastrointestinal tract and kidneys. Clinical improvement associated with reversibility of gastric amyloid deposition was observed in accordance with disappearance of the serum component of amyloid A protein. PMID- 2232369 TI - Alterations of glomerular filtration rate during cold exposure in progressive systemic sclerosis: measurement with technetium-99m DTPA. AB - We investigated the changes of the glomerular filtration rate (GFR) that occurred when the right hand was soaked in 7 degrees C water. The subjects were 5 patients with progressive systemic sclerosis who did not have clinical evidence of renal involvement. The clearance rate constant of 99mTc-DTPA, which is excreted by glomerular filtration, was measured with a cadmium telluride detector placed over the chest wall. In response to the cold exposure, the constant rose in 2 patients and remained unchanged in the remaining 3 patients. After termination of cold exposure, the constant fell in all 5 patients, suggesting renal Raynaud's phenomenon. These findings suggest that the renal vasculature in these patients has an abnormal response to cold exposure. PMID- 2232368 TI - A case of swallow syncope induced by vagovagal reflex. AB - A 65-year-old man experienced syncope associated with advanced atrioventricular (AV) block upon swallowing. Continuous electrocardiogram (ECG) monitoring revealed first and second degree AV block. ECG revealed advanced AV block (Max R R 6.38 s) upon swallowing, a cold drink. Demand ventricular pacing alleviated his symptoms. In this patient, the advanced AV block might have been precipitated by a vagovagal reflex triggered by expansion of the esophagus, resulting in selective suppression of the atrioventricular node. PMID- 2232370 TI - IgD multiple myeloma with renal involvement: case report. AB - IgD multiple myeloma is a unique type of multiple myeloma which is characterized by increased serum IgD and IgD type M-component in immunoelectrophoresis. It frequently shows renal involvement but it is a rare form of myeloma. The distinctive features of IgD myeloma are the dominance in males, high frequency in younger persons, and the uncertain appearance of M-component in serum electrophoresis. We experienced 3 cases of IgD multiple myeloma with renal failure which required hemodialysis before IgD myeloma was diagnosed. It is important to consider IgD myeloma when treating the patients with renal involvement of unknown origin. PMID- 2232371 TI - Immediate improvement of diabetic mononeuropathy after intravenous administration of prostaglandin E1. AB - The effects of intravenously administered prostaglandin E1 (PGE1) on diabetic mononeuropathy was investigated in three patients with diabetic oculomotor palsy. PGE1 (1.0-1.5 micrograms/day) was intravenously administered every morning for 4 or 6 weeks. Diplopia, blepharoptosis and decreased range of ocular movement, which were observed on admission, immediately began to improve at 1-4 days after the beginning of the treatment. On the final day of the treatment, none of the above signs remained in the three cases. The present study suggests that improvement of intraneural microcirculation by PGE1 administration results in an immediate recovery from diabetic oculomotor nerve palsy. PMID- 2232372 TI - Primary myelofibrosis terminating in megakaryoblastic crisis. AB - Primary myelofibrosis terminating in megakaryoblastic crisis is uncommon. A case with this condition is reported. The patient, a 62-year-old female, having had primary myelofibrosis for 13 years and a splenectomy 4 years before, was admitted because of high fever, hepatomegaly, thrombocythemia and leukocytosis. On admission, blasts appeared in the peripheral blood and thereafter gradually increased in number. The blasts were proven to be of megakaryocytic lineage. To our knowledge this is the third case of primary myelofibrosis terminating in megakaryoblastic crisis to be reported in Japan. PMID- 2232373 TI - [Two cases of pulmonary alveolar proteinosis with increased CEA]. AB - Two cases of pulmonary alveolar proteinosis (PAP) with increased CEA were reported. Case 1 was a 62-year-old male with suspected pulmonary fibrosis, who was transferred to our hospital. Laboratory findings on admission revealed 31.3 ng/ml of CEA. Because he had severe dyspnea, lung biopsy was not carried out. His condition gradually deteriorated and he died of respiratory failure. Autopsy revealed he had PAP and no malignancy. Case 2 was a 48 year-old male referred to our hospital because of dyspnea. Serum CEA was 52.8 ng/ml. Microscopic examination of a transbronchial lung biopsy showed PAP. The level of CEA in bronchoalveolar lavage fluid was 151 ng/ml. Unilateral whole lung lavage was performed twice. With the improvement of chest X-ray findings, serum levels of CEA fell to normal level. The molecular weight of CEA in bronchoalveolar lavage fluid was 180,000. Immunochemical staining of CEA in lung revealed nonspecific findings. PMID- 2232375 TI - [Williams-Campbell syndrome complicated by multiple meniscus signs in an adult case; is it a characteristic finding?]. AB - A 49-year-old woman visited our hospital for further examination of abnormal lung shadows in September 1984. She had suffered from pneumonia at the age of 3 years and had been treated for bronchial asthma until the age of 15. Many thin-wall cystic shadows were seen on her chest X-ray film in 1983. In July 1984, a mass like lesion with a meniscus sign appeared in one of the cystic shadows. The number and the size of similar lesions increased with worsening of productive cough. An infiltrative shadow was recognized in the left lower lobe in September 1987 and January 1988, but was resolved by treatment by ofloxacin. Frequent bacterial examinations of sputum and bronchial secretions revealed numerous Pseudomonas aeruginosa but no fungi. Serum antibody to Aspergillus fumigatus was negative and antifungal therapy was not effective. Bronchography showed many cystic dilated bronchi, which ballooned during inspiration and collapsed with expiration. The peripheral bronchi seemed to be normal. These findings along with her clinical course led us to make a diagnosis of Williams-Campbell syndrome. The mass-like shadows were considered to have arisen from viscid secretions that were rendered round by the characteristic movement of the ectatic bronchi. PMID- 2232376 TI - [Differentiation of intra-pulmonary lymph nodes from intra-pulmonary metastasis]. AB - In each case of primary or metastatic lung cancer, CT reveals multiple pulmonary nodules in addition to primary or metastatic lesions. All of these small pulmonary nodules were approximately 5 mm in size and were located in the subpleural region of a lower lobe of the lung. It was difficult to differentiate these small nodules from lung metastases. We were able to confirm that these nodules were subpleural intra-pulmonary lymph nodes by open thoracotomy. It should be noted that small pulmonary nodules in the subpleural region of a lower lobe of the lung might be intra-pulmonary lymph nodes. PMID- 2232374 TI - [An autopsy case of chronic pulmonary thromboembolism associated with congenital portal hypoplasty and pulmonary artery aneurysm]. AB - A 44 year-old woman died after a history of chronic right heart failure for 25 years. Roentgenological studies showed marked pulmonary aneurysm, and hemodynamics at rest revealed severe pulmonary hypertension. The diagnosis of chronic pulmonary thromboembolism was made by MRI which identified a high intensity mass in the dilated right pulmonary artery. At autopsy, a large organized thrombus adhered to the atherosclerotic pulmonary artery, and pulmonary thromboembolism or hemorrhagic infarction were identified. Microscopic examination revealed intimal and medial proliferation in small arteries and plexiform lesions. In addition, hypoplasty of the portal vein and portacaval shunt, which were thought to be congenital, were present. It has been recognized that the portacaval shunt can be attributed to pulmonary hypertension. In this case it was considered that the main cause of pulmonary thrombus formation was both pulmonary atherosclerosis and pulmonary artery aneurysm caused by prolonged pulmonary hypertension. This is the first case of chronic pulmonary thromboembolism associated with congenital hypoplasty of portal vein. PMID- 2232377 TI - [A case of simultaneous double cancer (lung and stomach cancer) related to asbestos exposure]. AB - A 76 year-old male with simultaneous double cancer (lung and stomach cancer) was reported. The patient was followed up for pleural plaque on chest X-ray from 1986. The diagnosis of stomach cancer was decided by biopsy and lung cancer by operation at the same time in 1989. The histology of these two tumors were different (stomach: well differentiated tubular adenocarcinoma, lung: moderately differentiated papillary adenocarcinoma) and the stomach cancer was early stage and lung cancer was stage IIIa. He had a definite history of asbestos exposure in Japanese naval shipyard. Pleural plaque with calcification was found on chest X ray and numerous asbestos bodies were detected in the resected lung tissue. Almost all asbestos fibers examined by an X-ray analyzer with scanning microscopy were chrysotile or tremolite. Furthermore, he was a heavy smoker (B.I., 1650). These tumors developed after 59 years of the first asbestos exposure. Asbestos exposure and smoking are considered to be important pathogenesis factors related to these two tumors. PMID- 2232378 TI - [Evaluation of FCR (Fuji Computed Radiography) images applied to standard radiography for the diagnosis of chest diseases]. AB - FCR (Fuji Computed Radiography) was added to plain chest radiography in order to evaluate its image characteristics and to determine the best image characteristics and to determine the best image processing program by comparing the visibility of shadows on conventional X-rays and on six FCR hard copy images processed by six mutually different image processing program. FCR showed excellent ability to visualize abnormal lung shadows as well as normal chest structures when processed by a moderate spatial frequency enhancement (spatial frequency 0.11 cycle/mm, level of enhancement). FCR also proved superior to the conventional film-screen system in the visualization of hilar and mediastinal structure as well as lung shadows. The effects of the image processing program on the visibility of shadow, granular and linear shadows were clearly demonstrated when a more intense spatial frequency enhancement (spatial frequency 0.18 cycle/mm, level of enhancement) was performed. The same results were obtained in terms of reticular and linear shadows and calcified lesions. On the contrary, low density shadows with poorly defined margins the lung field and infiltrates from mycoplasma pneumonia were well depicted by a program with a slightly steeper gradation (gamma; 1.0) and minimal frequency enhancement. Accordingly, FCR was found to be useful for the screening of abnormal chest X-ray shadows whereas it was also likely to demonstrate the best image when processed by the most appropriate image processing programs, depending on the characteristics of the shadows. PMID- 2232379 TI - [Analysis of patients with resected small-size (less than or equal to 2 cm in diameter) peripheral type lung cancer lesions]. AB - From 1953 to 1985, a total of 1289 patients with primary carcinoma of the lung underwent surgical treatment. Of these 116 (8.9%) had small-sized (less than or equal to 2 cm in diameter) peripheral type lung cancer lesions. This study had three purposes: 1) to analyse how small-sized lung cancer lesions were detected; 2) to evaluate the reliability of diagnosis of small-sized cancer lesions; and 3) to evaluate pre- and post-prognostic factors of such patients compared with patients with peripheral type lung cancer lesions 2.1-3 cm in diameter. Of the 115 patients with small-sized lung cancer lesions were detected in the course of mass surveys. Cytopathological diagnosis in 75% of the patients resulted from transbronchial brushing cytology. The 5-year survival rate of patients who underwent resection of small-sized peripheral type lung cancer lesions was 70% (2.1-3 cm; 52%). Various factors such as histologic type, nodal involvement, pleural involvement, pathological stage, and success of the operation were shown to significantly affect survival. A comparison of two groups, i.e., those with lesions smaller than 2 cm in diameter and those with lesions 2.1-3 cm in diameter, showed the rate of lymph node metastasis to be significantly different. Of the patients with peripheral lung cancer lesions smaller than 2 cm who underwent surgery, 21% had peribronchial, hilar, or mediastinal lymph node metastasis. On the other hand, lymph node metastasis was seen in 43% of cases with peripheral lung cancer lesions 2.1-3 cm in diameter who underwent surgery. PMID- 2232380 TI - [Reproducibility of peak expiratory flow rate measured at home]. AB - In 8 stable patients with chronic asthma, the reproducibility of peak expiratory flow rate (PEFR) measured and recorded 4 times per day for longer than 1 month at home and at work was assessed. Average %PEFRs of individuals through the periods observed were higher than 80%, and coefficients of variation were less than 10% regardless of the time measured. This suggested that a decrease in %PEFR more than 10% reflects early phase of deterioration of airways narrowing and frequent measurement of PEFR is essential for long-term management and for self-assessment of chronic asthma. PMID- 2232381 TI - [Respiratory pathophysiology during sleep in patients with myotonic dystrophy]. AB - Myotonic dystrophy is a genetic disorder inherited as an autosomal dominant trait. It is known to be associated with endocrine dysfunction, polar cataracts, cardiac abnormalities and other conditions. Respiratory distress constituents the principal problem in myotonic dystrophy. The author investigated postural change of respiratory function in 12 patients with myotonic dystrophy (MYD), and 7 patients with limb-girdle dystrophy (LG) and overnight polysomnography was performed on 10 patients with MYD and 5 patients with LG. The respiratory function in seated posture showed no significant difference between LG and MYD, but in patients with MYD, the vital capacity and the expiratory reserve volume in a supine posture was reduced in comparison to that during seated posture. However, the respiratory function in patients with LG was not significantly different in seated and supine postures. Also, in patients with MYD, there was a significant decrease in arterial PO2 from the seated posture to the supine posture, without a significant change in the arterial PCO2. However, in patients with LG, there was no significant change in arterial blood gas analysis parameters. It was speculated that these findings concerning respiratory function and blood gas analysis in patients with MYD were caused by the involvement of the diaphragm. In the supine posture, the diaphragm shifted to the cranial position because of the abdominal contents rising into thorax, therefore the lung volume was reduced and the ventilation-perfusion ratio deteriorated. The changes of respiratory function parameters and PaO2 were partly responsible for the hypoxemia observed during sleep in patients with MYD. Overnight polysomnography showed that 9 of the 10 patients with MYD and 1 of the 5 patients with LG presented apneas during sleep, particularly during REM, stage 1 and stage 2. Almost all apneas were central type, with a low percentage of obstructive apneas and the apnea index was 19.0/h (mean) in MYD, 6.5/h in one case of LG. These result strongly suggest that sleep apnea is of central origin, but the distinction between a central and an obstructive etiology is difficult in neuromuscular disease and particularly when a disorder of central ventilatory responsiveness is suspected. The respiratory function of MYD and LG in seated and supine postures was studied and overnight polysomnography performed. It was emphasized that it was important for the respiratory care of neuromuscular disease to consider the influence of postural changes in the respiratory function. The present series of studies revealed central sleep apnea in the patients with myotonic dystrophy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2232383 TI - [The possible involvement of immune complexes in pulmonary granuloma formation in experimental hypersensitivity pneumonitis]. AB - Hypersensitivity pneumonitis (HP) is a disease caused by inhaled organic dust. The alveolitis and granuloma are characteristic features of HP. The precise mechanism of granuloma formation is still unclear. The roles of immune complexes and primed T cell in relation to granuloma formation were studied. Local lymph node cells were obtained from C57BL/6 mice immunized by injection of ovalbumin (OA) or keyhole limpet haemocyanin (KLH) emulsified in complete Freund's adjuvant into footpads. Thereafter enriched T cells were obtained by passage through nylon wool columns. Antigens (OA, KLH) were chemically coupled to Sepharose 4B beads (OA-beads, KLH-beads). The immune complex was made by the incubation of the antigen-coupled beads and the immunized mouse serum at 37 degrees C for 2 hours. The recipient mouse irradiated by 6.5 Gy was transferred with 3 X 10(7) T cells and challenged with intratracheal instillation of 1 X 10(4) antigen-coupled beads or 1 X 10(4) immune complex-coupled beads. The recipient mice were sacrificed day 3 after cell transfer and challenge. The radius of pulmonary granuloma was measured by microscopic examination of the HE-stained section. The radius of granuloma increased in the recipient mouse which received the primed T cell and was challenged with immune complex-coupled beads compared with any other combination of cell transfer and antigen challenge. This result suggests that not only T cell but also immune complexes play an important role in granuloma formation in HP. PMID- 2232382 TI - [Echo guided percutaneous needle biopsy for diagnosis of thoracic lesions]. AB - Echo guided percutaneous needle biopsy was performed in 32 cases with thoracic lesions. A definitive diagnosis was made histopathologically in 11 (100%) of 11 malignancies, 4 (67%) of 6 benign tumors and 7 (47%) of 15 inflammatory lesions. Furthermore, using cytological specimens, definitive diagnosis was successfully made in 10 (91%) of 11 malignancies and 1 (17%) of 6 benign tumors. Such highly accurate diagnostic rates were due to 1) the accurate puncture of the lesions under real time sonographic guidance, 2) repeated biopsy in case in which sample was inadequate for cytological diagnosis, and 3) aggressive application of needle biopsy for histopathological diagnosis. Following this procedure, three patients suffered from a minor pneumothorax. To prevent pneumothorax, great care is necessary, especially in high risk cases, such as with a pneumatic pattern and thin lesion. One patient suffered from minor hemoptysis but recovered without any medication. No complications were noticed in cases of extrapulmonary lesions. We conclude that echo guided percutaneous needle biopsy is not only a complementary method for biopsy of mediastinal, peripheral pulmonary and chest wall lesions, but due to its simplicity and convenience, it should be a routine method for biopsy of thoracic lesions. PMID- 2232385 TI - [A case of massive hemoptysis occurring after lung injury due to a torn segment of pleural calcification]. AB - A 64-year-old man was referred to our hospital because of little improvement of hemoptysis lasting three days after drug therapy. A chest roentgenogram and fiberoptic bronchoscopic examination performed on the second hospital day when the patient experienced a massive hemoptysis of about 2,000 ml revealed arterial bleeding from the left upper lobe. Even after extensive embolizations of the left upper bronchial, the first, second, third and 4th intercostal arteries, the patient's hemoptysis did not improve. On the 73rd hospital day the patient underwent left upper lobectomy. Macroscopic and microscopic examinations in the resected specimen revealed lung injury due to a torn segment of pleural calcification after tuberculous pleuritis, resulting in the massive hemoptysis. Although physicians encounter many patients complaining of hemoptysis and/or hemosputum, this case is considered to be very rare. PMID- 2232384 TI - [A case of Swyer-James syndrome diagnosed at age 70]. AB - A male case of Swyer-James syndrome, who had been followed for bronchiectasis for a long time, detected at age 70 and diagnosed by radiological studies was reported. The movement of his left diaphragm was impaired. Arterial oxygen tension was 68 torr while breathing room air. Pulmonary function tests showed mixed ventilatory impairment, increase of residual volume, and uneven gas distribution, but diffusing capacity was normal with the single breath method. Chest radiograph revealed hyperlucency of the left lung and the right middle lung field. In these areas, pulmonary angiography showed marked hypovascularity and diffuse vascular atrophy, and perfusion and inhalation scans also showed marked decreased perfusion and ventilation. Pulmonary hypertension was not detected by right heart catheterization. Fiberoptic bronchoscopy was performed and showed no abnormality of the left bronchial tree, and bronchography demonstrated diffuse cylindrical bronchiectasis of the left lung with no alveolar filling. He had suffered from chronic sinusitis for a long time, which might suggest that he had sinobronchitis due to congenital abnormality of the airway and this caused continuous respiratory infection, which could cause this syndrome. Including our own case, about 80 cases of Swyer-James' syndrome have been reported in Japan. But only 4 cases were above 70 years of age and all of them were male, and there has been no female cases above age 50. Males predominate over females, and in both sexes the left lung was more commonly affected than the right. PMID- 2232386 TI - [A review of coronary artery bypass grafting distal to the total obstruction]. AB - Coronary artery bypass grafting (CABG) distal to the total obstruction has been carried out in 10 patients during 17 month period. There were neither operative deaths nor perioperative myocardial infarction. All patients were free from angina pectoris postoperatively. There were 13 completely obstructed coronary arteries. CABG was successfully placed on 9/9 (100%) of the distal artery filled with collaterals including thread-like caliber, but 0/4 (0%) without opacification suggesting no collaterals. The graftability to the left anterior descending branch was 6/6 (100%), to the circumflex system was 3/5 (60%), and to the right coronary system was 0/2 (0%). Postoperative regional ejection fraction and cardiac index improved significantly. In conclusion, CABG distal to the total obstruction should be performed in case of the distal lumen opacified by collaterals. Especially CABG to the left anterior descending artery might be worth-while. PMID- 2232387 TI - [A study of five cases of traumatic diaphragmatic rupture]. AB - During the last 5 years, 5 cases of traumatic diaphragmatic rupture were surgically treated. These cases were reported and the literature concerning traumatic diaphragmatic hernia in the last one decade in Japan, including 80 cases was studied. The purpose of this study is to discuss the most important early diagnostic tools and to consider the choice of incision and approach. The following two results were gotten. (1) Plain chest X-ray, computed tomography and ultrasonography were the most valuable diagnostic tools. (2) The choice of incision and approach depends on the stage at which the rupture is recognized (early or late), the site of rupture and associate injuries. PMID- 2232388 TI - [The effects of pulsatile pumping on tissue perfusion and renal function during deep hypothermic low flow perfusion]. AB - The effects of pulsatile pumping on tissue perfusion and renal function during deep hypothermic low flow perfusion were compared with non-pulsatile pumping. Twelve dogs were classified into 2 groups by the perfusion technique used. Animals were core cooled to 20 degrees C esophageal temperature with 80 ml/kg/min perfusion rate and maintained at the level for 2 hours with low flow perfusion (LFP) (30 ml/kg/min), then rewarmed to 35 degrees C with 80 ml/kg/min flow rate. As compared with the non-pulsatile group, pulsatile group demonstrated greater urine output during rewarming (p less than 0.05) and greater lymph flow during core cooling (p less than 0.05). The non-pulsatile group showed higher lymph/plasma protein concentration ratio (Lc/Pc) during LFP and rewarming (p less than 0.05), and greater plasma protein clearance during rewarming (p less than 0.05), and much higher increase of interstitial fluid pressure. The lesser water retention during bypass was also noted in the pulsatile group (28.6 +/- 27.6 ml/kg vs 85.4 +/- 52.1 ml/kg, p less than 0.05). These findings have suggested that the pulsatile perfusion may be useful for the infant cardiopulmonary bypass reducing tissue edema and preserving better renal function. PMID- 2232389 TI - [The method of fixation of intra-aortic balloon catheter in the iliac artery without sheath introducer]. AB - This paper showed the procedure of fixation of intra-aortic balloon without sheath. For this purpose, we found to use Implantaid Lead Introducer (peel away type). This introducer can be removed from balloon catheter after insertion into iliac artery. Consequently, the incidence of thromboembolism of iliac artery and complications such as myonephropathic metabolic syndrome may be decreased. PMID- 2232390 TI - [A surgical case of eventration of diaphragma in ten-year-old boy: a newer approach of operative correction of eventration]. AB - A ten-year-old boy was admitted to our hospital for surgical treatment of eventration of diaphragma. He had operative correction of eventration with intrathoracic approach and recovered good health. We present a newer method of operative correction of eventration, which can be beneficial in prevention of "re eventration", especially, on younger patients. PMID- 2232391 TI - [Prosthetic valve endocarditis]. AB - From January/1983 to March/1988, 28 patients were submitted to valve replacements for prosthetic valve endocarditis in 1,512 valve replacements. Seventeen patients were male, their mean age was 36.7 +/- 12.9 years old, and eight cases were operated under emergency condition. The blood cultures were positive in 14 (50%), the agent most commonly found being Streptococcus viridans in 5 cases. Hospital mortality was 28.5%. The causes of death were septicemia in 4 cases, low output syndrome in 2 cases, cerebrovascular accident in 1 case, and coagulopathy in 1 case. Mortality was higher with statistical significance in the cases whose blood cultures were negative, the cases in which the time from valve replacement to the onset of endocarditis was less than one year, and the cases under emergency condition. PMID- 2232392 TI - [Torsion after left lower lobectomy and cerebral infarction following the re exploratory thoracotomy: a case report]. AB - A 38-year-old man had a left lower lobectomy for pulmonary carcinoid. Following the operation, torsion of the left residual upper lobe occurred. Re-explosive thoracotomy was performed on the second postoperative day. The left upper lobe showed a clockwise 180-degree rotation. Pneumonectomy was not done. After the re thoracotomy, the patient developed right hemiplegia. Head CT showed a cerebral infarction due to the thrombus of pulmonary vein that was released after the repair of the torsion. PMID- 2232393 TI - [A case of an operation for lung cancer after PTCA]. AB - A 64-year-old lung cancer patient combined with angina pectoris was admitted to our hospital. Chest roentgenogram showed a coin lesion in the left upper lobe. Broncho-fiberscopic examination proved adenocarcinoma. Coronary angiography revealed 90% stenosis of the left circumflex artery. Percutaneous transluminal coronary angioplasty (PTCA) was done and resulted in success. Eight days after PTCA, left upper lobectomy for lung cancer was undergone. Postoperative course was uneventful. Compared with coronary artery bypass grafting, PTCA was very useful for the patient having malignant disease combined with angina pectoris because of little surgical stress and no delay of operation. PMID- 2232394 TI - [A case report of isolated congenital tricuspid regurgitation]. AB - Reports of isolated congenital tricuspid regurgitation are very rare. A 20-year old female with severe tricuspid regurgitation was reported. The patient was admitted to our hospital with complaints of easy fatigability and palpitation. Right ventriculogram showed severe tricuspid regurgitation. She was treated with tricuspid valve replacement with a 33 mm bioprosthetic valve. Seven surgical treated cases of isolated congenital tricuspid regurgitation including our case were collected from literature and reviewed. PMID- 2232395 TI - [Myocardial infarction complicating left ventricular free wall blowout rupture: a survival case after surgical repair]. AB - A 58-year-old man who suffered from acute myocardial infarction complicated with left ventricular rupture and subacute pericardial tamponade was reported. On admission, echocardiography strongly suspected presence of intrapericardial fluid. And immediate pericardiocentesis proved left ventricular free wall rupture (LVFWR). Coronary angiography with the support of IABP revealed occlusion of LAD (# 8). Percutaneous transluminal coronary angioplasty was performed with partial success. After pericardiotomy, the hemodynamic state was improved, however, 2 hours later, his blood pressure fell down to 40 mmHg suddenly. Emergent operation (re-mediastinumotomy+ ) was performed under the suspicion of left ventricular blowout rupture with the direct closure of the perforated site with 4 woven Dacron pledgets at bedside in ICU. The patient ran an uneventful postoperative course and is now doing well. Clinical and therapeutic features of LVFWR were discussed. PMID- 2232396 TI - [Report of a case successfully weaned from long left ventricular assist with complete recovery after coronary artery bypass grafting]. AB - A 45-year-old female underwent coronary artery bypass grafting (CABG) due to medically uncontrollable unstable angina. After completion of CABG, left ventricular contraction was remarkably diminished to maintain systemic circulation. Because intraaortic balloon pumping and veno-arterial bypass with large amount of catecholamines could not improve left ventricular wall function, we decided to use left ventricular assist device (LVAD). After application of LVAD, the patient could easily be weaned from cardio-pulmonary bypass. LVAD was used for 25 days and the patient was successfully weaned from LVAD too, and are now living 6 months postoperatively. As far as we know, this case is the first survival patient after the longest cardiac assist in our country. PMID- 2232397 TI - [A case of infective endocarditis with hemorrhagic fibrinous pericarditis]. AB - A case of infective endocarditis which was complicated with hemorrhagic fibrinous pericarditis was reported. The hemorrhagic fibrinous pericarditis is a rare complication of infective endocarditis of the aortic root and is observed massive hemorrhage into the pericardial space. These patients should be considered for the aortic valve replacement early in the course of the disease. PMID- 2232398 TI - [A case of ventricular septal perforation with bidirectional shunt and Hegglin like syndrome]. AB - A 47-year-old man with ventricular septal perforation (VSP) was repaired successfully. His preoperative examinations revealed Hegglin like syndrome with fixed and split second heart sound due to early closure of aortic valve (QT-Q II A = 58 ms), and bidirectional shunt through the VSP. These abnormal phenomena occurred due to shortening of left ventricular ejection time and prolongation of right ventricular ejection time, and were completely abolished after the operation. PMID- 2232400 TI - [Experience of the malignant complete intrathoracic goiter: discussion on 13 cases of Japan]. AB - A 56-year-old woman was found to have a mediastinal mass on routine examination. Chest X-ray, CT scan, MRI and superior vena cavography showed a right upper mediastinal tumor invading the SVC. And it was diagnosed malignant intrathoracic goiter by histological examination by percutaneous needle biopsy. On thoracotomy and mediastinotomy, the tumor located only in the right upper mediastinum and had no relation to the cervical thyroid gland. Histological examination revealed papillary adenocarcinoma. We reported a malignant complete intrathoracic goiter and added discussion on another 12 cases seen in Japanese literature. PMID- 2232399 TI - [Double chambered right ventricle: surgical experience in a 60-year-old woman]. AB - The patients reported as double chambered right ventricle are mainly children. A 60-year-old woman had been pointed out for her systolic cardiac murmur without any symptom. She was admitted to our hospital for her gradual onset of fatigue, lassitude. Cardiac catheterization data revealed a 105 mmHg peak-to-peak gradient within the right ventricular cavity with normal pulmonary pressures [20/5 (12) mmHg]. Right ventricular end-diastolic pressure was 4 mmHg. Right ventriculogram demonstrated double chambered right ventricle. Electrocardiogram showed neither right ventricular hypertrophy nor upright T wave in V3R. In order to release intraventricular pressure gradient and her symptom, the anomalous muscle bundles were resected through both the right atrium and the pulmonary artery. Surgical repair without right ventriculotomy is suitable for such an elder patient with double chambered right ventricle whose ventricular function may decrease. PMID- 2232401 TI - [A rare case of airway foreign bodies complicated with flail chest following traffic accident]. AB - A 30-year-old man was taken to the emergency room of this hospital because of chest injury following traffic accident. On arrival he was found to be dyspneic due to multiple rib fractures (flail chest) and tension pneumothorax on the left, and was intubated immediately concomitantly with a chest drainage. During the management with the respirator, he was also noticed to have continuous bleeding from the airway. The X-ray film of the chest showed a suspicion of foreign materials on the right hilar region and subsequent bronchoscopic examination revealed the presence of several fragments of a broken windshield in the bronchial trees. Nine fragments were removed bronchoscopically. Tracheal tube was extubated on the 14th day and he was discharged on the 28th day without any sequela. PMID- 2232402 TI - [Successful surgical treatment of ruptured thoracic aortic aneurysm into the lung]. AB - A 62-year-old man was admitted to the hospital because of massive hemoptysis. Chest X-ray film, CT scan and IADSA demonstrated a large aneurysm of the thoracic aorta, extending from the ascending aorta to the descending aorta. Bronchoscopy revealed bleeding from left B1+2. Six days after the onset, replacement of the thoracic aorta with woven Dacron prosthetic graft, autoclaved after immersion in albumin, was performed with cardiopulmonary bypass and separate cerebral perfusion (700 ml/min) under moderate hypothermia (25 degrees C). Left upper lobe of the lung, adherent tightly to the posterior and medial wall of the aneurysm, was not dissected because bleeding from left bronchus was trivial even after systemic heparinization. Because of the cardiac dilatation, delayed chest closure was needed. Postoperative cardiac failure, necessitating much catecholamine support, was seen with gradual improvement and no neurological deficit was recognized. He was discharged from the hospital without any sequelae 2 months after the onset. Pathologic diagnosis was an atherosclerotic aneurysm. PMID- 2232403 TI - [New trends in urodynamic investigation]. AB - Urodynamic approach to the disorders of the urinary tract has been based on the knowledge of anatomy and neurophysiology of this abnormality. The development of this field included uroflowmetry, cystometry, urethral profilometry, and electromyogram of the external sphincter. In addition to these investigations new trends in urodynamic field were reviewed. With the advent of muscle biochemistry intra-renal urodynamics has been advocated. These researches would be expected to clarify the mechanism of intra-renal reflux. The another investigation was urophonography. When the urine passed through the posterior urethra the urethral sound occurred. The detecting, recording and analyzing systems were developed. This method would be entirely a new method of urodynamic study. PMID- 2232404 TI - [A study of the native kidneys in patients with chronic renal failure. Report 1: Morphological changes and occurrence of acquired cysts of the native kidneys in patients with chronic renal failure]. AB - As morphological changes of the native kidneys, the presence of acquired cysts, intra-renal calcification and renal tumor was investigated mainly by ultrasonography and computed tomography in 151 patients with chronic renal failure. 1) Among 140 uremic patients caused by medical diseases. 40 patients had simple cysts, and 37 had acquired cystic disease of the kidneys (ACDK). However 4, uremic patients caused by urological diseases were not seen to be with an acquired cysts. 2) The patients with ACDK were with significantly longer durations of dialysis therapy than those with simple cysts or no cysts. Furthermore, the patients with ACDK were younger than those of the other groups. 3) Intra-renal calcification was more frequently found in patients with cystic disease (simple cyst, ACDK and polycystic disease) than in those without cystic disease with statistic significance. 4) Native kidneys became larger after the occurrence of ACDK. 5) Three cases of renal tumor were found. PMID- 2232405 TI - [A study of the native kidneys in patients with chronic renal failure. Report 2: Correlation between cystic changes in native kidneys and development of renal tumor]. AB - The factors which made acquired cysts develop to renal tumors in chronic hemodialysis patients was investigated from clinical and histological findings. Although three renal tumors were found among 151 patients with chronic renal failure, clinically, one case had acquired cystic disease of the kidneys (ACDK), one case had simple cysts and the other case did not have any cyst. However, the last two cases had multiple small cysts histologically. In ACDK, renal tubules were degenerated and dilated, fused to each other, forming more larger cysts. Furthermore, epithelium of acquired cysts showed columer and dysplastic change, and papillary adenomas were developed into the inner space of the cyst wall. And ACDK kidney without renal tumor also revealed the same findings in histological examinations. It was postulated that renal tumor occurred from the papillary projections of the dysplastic epithelium of cysts. Therefore cysts in uremic patients seemed to be different from the simple cyst in normally functioning kidneys. PMID- 2232406 TI - [Clinical application of compact ESWL (Direx Tripter X-1)]. AB - Clinical trials using Extracorporeal Shock Wave Lithotripter (Tripter X-1) were performed on 30 cases for upper urinary tract calculi (16 cases: renal stone, 14 cases: ureter stone) with one trial per individual case from December, 1988 till February 1989. The fragmentation rate of 100% resulted. One month after treatment, evaluation on the X-ray film showed that 10 cases (33%) were found to be excellent where stone silhouette was no more observed. Effective cases where residual stone having dimension of below 5mm counted 10 (33%), and clinically effective rate, sum of both excellent and effective rates was 67 percent. Effective rate was 75 percent in case of kidney stone, and 57 percent in case of ureter stone respectively. Side effects of visual hematuria, skin ecchymosis and fever were observed, yet none of them was of serious grade, and post operative changes in blood chemistry were mild and transient. No remarkable side effects due to radiation exposure were observed. We concluded therefore that Extracorporeal Shock Wave Lithotripsy by this system is an effective therapy for upper urinary tract stones. PMID- 2232407 TI - [Evaluation of serum S100ao protein in patients with renal cell carcinoma]. AB - In order to evaluate the clinical significance of S100ao protein, we measured serum S100ao protein in 36 patients with renal cell carcinoma by EIA developed by Kimura et al. In addition, the distribution of S100ao protein was studied by the immunohistochemical method. Previous study demonstrated that mean level of serum S100ao protein in healthy volunteers was 203 +/- 107 pg/ml, therefore the cut off level was set to 524 pg/ml. The results obtained in this study were as follows: 1) The mean level of serum S100ao protein was 1162 +/- 2056 pg/ml, and its positive rate was 44% in 36 patients with renal cell carcinoma. When the patients were divided into 2 groups according to tumor stage, the mean level of serum S100ao protein in the high stage group was significantly higher than that in the low stage group (p less than 0.01). 2) In the sequential study of serum S100ao protein, patients with progressive disease showed a gradual increase in the level of serum S100ao protein while patients with no evidence of tumor showed a normal level of serum S100ao protein. 3) There was no correlation between the level of serum S100ao protein and the histological grade of renal cell carcinoma. 4) Immunohistochemical analysis (10 cases) showed that S100ao protein was observed in all of 10 renal cell carcinomas. Thus, the present study suggests that serum S100ao protein might be a useful clinical marker especially in monitoring patients with renal cell carcinoma. PMID- 2232408 TI - [Ultrasonographic study on kidneys in patients with chronic renal failure. Part I. Ultrasonic measurement of renal size and analysis of renal ultrasonotomograms]. AB - Ultrasonograms of 546 kidneys were obtained in 280 patients undergoing chronic dialysis. Dialysed kidneys could be detected in 529 of the 546 kidneys (96.9%) by ultrasonic examination. The ultrasonic diagnoses on dialysed kidneys were contracted kidney in 313 kidneys (59.2%) and acquired cystic disease of the kidney in 107 kidneys (20.2%). Ultrasonic measurement of the size of kidney (length and thickness) revealed that the kidneys in patients with chronic renal failure were much smaller than normal ones. But the kidneys in patients undergoing dialysis for more than 8 years gradually increased in size with incidence of acquired renal cysts. The kidneys in patients with diabetic nephropathy were greater in length and thickness than those with chronic glomerulonephritis. Sonographic features of dialysed kidneys were unclear renal imaging, unidentified central echoes, cortico-medulla + border and increased parenchymal echogenicity. Irregularity of the renal contour had a tendency to increase in number with incidence of cysts in long-term dialysis patients. The ultrasonograms of the kidneys with diabetic nephropathy showed fewer changes than normal ones. No major complication of the kidney was detected in the present study. However, two retroperitoneal hematomas and one renal cell carcinoma developed within two years after this examination. We believe that regular screening of the kidneys by ultrasonic examination is mandatory in patients on chronic dialysis for early diagnosis and treatment of these complications. PMID- 2232409 TI - [Ultrasonographic study on kidneys in patients with chronic renal failure. Part II. Acquired cystic disease of the kidneys]. AB - Ultrasonic examination of the kidney was performed on 280 patients undergoing chronic dialysis. Acquired cystic disease of the kidney (ACDK) was detected in 107 of 529 kidneys (20.2%). This paper presents an analysis of ultrasonotomograms of ACDK. Ultrasonic measurement of the size of ACDK was 72.5 +/- 15.2 mm in length and 41.7 +/- 9.8 mm in thickness. The size of ACDK was significantly greater than that of contracted kidneys by ultrasonographic diagnosis. With regard to sex distinction the length and thickness of ACDK were significantly greater in males than in females. As for laboratory data, patients with ACDK showed significantly higher values of red blood cell count, hematocrit and serum creatinine concentration compared with contracted kidneys. Prolongation of the dialysis peirod increased the incidence of ACDK. The size of ACDK showed a tendency to increase with duration of dialysis. However, no correlation was noted statistically between the incidence of ACDK and duration of dialysis and between the size of ACDK and duration of dialysis. There was a significantly lower incidence of ACDK in patients with diabetic nephropathy than those with chronic glomerulonephritis. A sonographic feature of ACDK is irregularity of the renal contour because of cystic transformation. Renal imaging, identification of the corticomedullary border, identification of the central echoes and increased parenchymal echogenicity were similar to other dialyzed kidneys. The main complications of ACDK are hemorrhage and tumor formation. We observed two retroperitoneal hematomas and one renal cell carcinoma developed within two years after this examination. The incidence of complications of ACDK was 5.1 per cent. We believe that patients with ACDK should be watched carefully by regular ultrasonic examination for early diagnosis and treatment of these complications. PMID- 2232410 TI - [Clinical evaluation of bone turnover in patients with bone metastasis of various cancer of urogenital tract]. AB - To study the bone turnover in patients with bone metastasis from cancers of the kidney, bladder, prostate and other organs, Ca metabolism, vitamin D related hormones and various markers, such as bone glaprotein (BGP) and hydroxyproline, were investigated. In the group with osteolytic metastasis of non-prostatic cancer patients, BGP which is a measure of bone absorption was significantly increased and urinary excretion of hydroxyproline, Ca and P was elevated. Serum Ca was also higher and 1 alpha 25 (OH)2D and 250HD, measures of the metabolism of vitamin D, were lower. It was shown that bone absorption was promoted with the osteolytic findings by clinical X-ray examination, but osteoblastic changes which did not depend on osteoblast cells, seemed to exist in this group. On the contrary, in the group with osteoblastic metastasis from prostatic cancer, the level of BGP was not increased, but urinary hydroxyproline was moderately increased. Serum and urinary Ca and P levels were increased. In addition, 1 alpha 25 (OH)2D and 24 x 25 (OH)2D were lower than in the control group. These results indicate that urinary hydroxyproline is a useful marker for patients with bone metastasis, but BGP was correlative with neither the clinical findings of bone metastasis nor the bone turn over and metabolisms. PMID- 2232411 TI - [Long-term bioeffects of extracorporeal shock waves on renal tissue and blood pressure in normotensive and spontaneously hypertensive rats]. AB - In order to examine chronic effects of shock waves on renal structure and blood pressure, normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were uninephrectomized and shock waves were given on the lower half of the residual kidney by Piezolith with the focus pressure of 1020 bar. In the first experiment, 36 WKY were divided into 6 groups; Group 1 served as control, Group 2, 4 and 6 received a single session of 1250, 2500 and 5000 shocks, respectively, whereas the animals in Group 3 and 5 received repeated dose of 1250 or 2500 shocks within 3 days after the first session. All the animals in Group 6 died within 48 hours due to remarkable renal hemorrhage, leaving only 5 Groups for the evaluation of long-term study. The blood pressure, measured by tail-cuff method 60 days after shock wave administration, was not significantly different between the control and shock-waved WKY. Neither was there any remarkable difference between the blood pressures measured prior to and 60 days after the intervention in each Group. At 16th week after the shock wave administration, the animals were sacrificed. There was a slight but statistically significant increase in serum creatinine level in Groups 2, 4 and 5, as compared to the level of control animals in Group 1. On light microscopic sections, there was no remarkable histological change in the kidney of Group 2, however, the renal parenchyma was frequently replaced with interstitial fibrosis in Groups 3, 4 and 5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232412 TI - [Partial sacral agenesis. Characteristics of urodynamic findings]. AB - We investigated fifteen patients with partial sacral agenesis who complained of urological disorders. Those with a myelomeningocele were not included. The mean age at the first visit was 13 years old. Bilateral and unilateral sacral agenesis were observed in nine and six patients, respectively. Chief complaints comprised incontinence and/or nocturnal enuresis in 10 patients, pollakisuria 5, recurrent fever attack due to urinary tract infection 5 and difficulty in micturition 2. In 4 cases vesicoureteral reflux was observed. At an initial urodynamic study bladder compliance varied from 1.4 to 37.0 (mean 10.4) ml/cmH2O and uninhibited contractions were present in 10 of them. Three patients were judged to have normal or almost normal bladder function. After treatment with clean intermittent catheterization and/or anticholinergics, compliance improved to a mean of 15.1 ml/cmH2O and the uninhibited contraction decreased in its amplitude or disappeared completely in 8 of 10 cases. It was suggested that patients with partial sacral agenesis originally suffered from a lower motor neuron lesion. The severity of the sacral deformities and other neurological symptoms (gait or sensory disturbance) were not related with the urodynamic findings. However, it was found that the more the cystogram was deformed the lower was the bladder compliance. PMID- 2232413 TI - [Immunological study on chyluria]. AB - Immunological studies were performed in 87 patients with chyluria referred to our clinic from January 1982 to December 1988. White blood cell count in 78 patients was 5210.3 +/- 1440.9/mm3. The fraction and the number of lymphocyte were 18.7 +/ 9.5% and 934.1 +/- 521.6/mm3, respectively: they were lower than normal limit. The percentages of T and B lymphocytes studied in 46 patients were 79.3% +/- 11.2% (normal range: 76-86) and 10.4 +/- 7.9% (normal range: 8-16), respectively: both lymphocytes tended to decrease in percentage. Lymphocyte blast formation stimulated with phytohemagglutinin (PHA) was carried out in 20 patients. The mean of the blast formation was 17410.0 +/- 10275.1 c.p.m. (normal range: 377700 62400), and much lower than normal value. Of 22 patients who had PPD skin test, only 9 (40.9%) were positive. These findings signified that cellular immunity was suppressed in patients with chyluria. On the other hand, the value of immunoglobulin was within normal range (IgG: 1325.3 +/- 475.6 mg/dl, IgA: 242.0 +/- 98.3 mg/dl, IgM 130.4 +/- 95.9 mg/dl). Study on the values of laboratory examinations showed statistically positive correlation between total lymphocyte population and T cell number, and between total lymphocyte population and lymphocyte blast formation. In patients with chyluria, serious sequelae have not been reported. However, care should be taken for possible opportunistic infection and, particularly, malignant tumors because suppression of cellular immunity may be one of the promoting factors of malignant tumors. PMID- 2232414 TI - [Prognostic factor for prostate cancer. Gunma Urological Oncology Study Group]. AB - The study of prognostic factors in patients with prostate cancer (Pca) may be of value in understanding the natural history of the disease and may also assist in planning and analyzing the results of clinical trials. Moreover some information through this study would be beneficial to assessing the prognosis and decision of better therapy form of individual patients. The significance of items studied was evaluated from the two view points, survival rate and Pca death rate. Stage, pathological differentiation and acid phosphatase were significantly related to them, in the category grade depending manner. Past history and complication, and age were also significantly related to them but higher category grade as a survival factor showed lower Pca death rates. ESR, gait disturbance and hematuria were related to only survival rate. Any significant relationship was not observed in serum testosterone, voiding disturbance and cancer-pain. Prognostic factors should be clinically used through the well understanding of each characteristics. This paper also showed that statistical significance not always provide a wide difference between categories compared. PMID- 2232415 TI - [Study on small renal cell carcinoma diagnosed by ultrasonography]. AB - Sixty-seven patients underwent a resection of renal cell carcinoma in our hospital between July 1984 and Mar. 1989. Out of them 31 patients with small renal cell carcinoma less than 4 cm in diameter were examined. The proportion of small renal cell carcinoma to all renal cell carcinoma was 36% (14 patients) in the first half period (July 1984-July 1987) and 61% (17 patients) in the last half (Aug. 1987-Mar. 1989), i.e. in total more than half of all the carcinomas. The patients diagnosed by ultrasonographic screening were 25 (80%) out of the 31 patients. The incidence of small renal cell carcinoma was 4 (0.06%) out of 6892 patients in our health check-up center and 6 (1.0%) out of 610 hemodialysis patients, and they were found by ultrasonic examination. The carcinoma was protruded from the renal contour in 24 patients (77%) and was inside the renal parenchyma (23%) in 7 patients. The carcinoma in the 24 patients was associated with the deformity of its outline. The patients with a positive IVP were 5 out of 31 patients and the carcinoma in 4 out of the 5 patients was inside the renal parenchyma. Of all patients with protrusion of te renal contour, only one patient was with a positive IVP. The above findings indicate that ultrasonic examination is a useful method for the early diagnosis of small renal cell carcinoma. PMID- 2232416 TI - [Follow-up of 104 children with "primary" VUR. Incidence of unstable bladder, its impact on resolution of VUR and progression of renal scar]. AB - One hundred and four children (48 boys and 56 girls, ranging in age from 3 months to 15 years, and follow-up period of more than 2 years in all) with "primary" vesicoureteral reflux (VUR) were retrospectively analyzed with particular emphasis on resolution of VUR and occurrence of renal scar. All underwent cystoscopic examinations which failed to demonstrate any organic vesicourethral obstruction, and all were neurologically normal. The patient population was divided into 2 groups based on cystometric findings. Group 1 consisted of 74 patients with unstable bladder and Group 2 consisted of 30 patients without unstable bladder. Although both groups were initially kept under antibacterials, in Group 1 frequent voiding and anticholinergics were maintained until the bladder stabilized by itself. There was no difference in the grade of reflux between the two groups. The rate of spontaneous resolution of reflux was 18% in group 1 in which more than 60% of the patients were with high grade reflux, while in Group 2 it was 17%, similarly to Group 1, but all were with low grade reflux. The presence or absence of renal scar and its subsequent evolution were determined in 73 patients in whom serial urograms were available enough to evaluate nephrographic renal outline. The incidence of renal scar at the first visit was 26% in Group 1 and 36% in Group 2. New formation of renal scar was not found in either group. The progression of preexisting renal scar was seen only in Group 1 (5/55 patients, 9%), and not in Group 2 (0/18 patients, 0%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232417 TI - [Percutaneous endoscopic surgery for obstructive diseases in the upper urinary tract--preliminary report]. AB - Fifty-two patients with obstructive diseases of the upper urinary tract were treated by percutaneous endoscopic surgery between May, 1986 and July, 1989. Fifty-nine procedures consisting of endopyelotomy (24 procedures), endopyeloureterotomy (29) and balloon dilation under direct vision (6) were performed in 54 units of the urinary drainage system. Causative diseases were congenital in 24 units, scar due to calculi in 17, scar due to previous surgery in 11 and tuberculous ureteritis in 2. The postoperative follow-up periods ranged from 3-41 months, mean +/- S.D.; 12.2 +/- 7.3 months. Of the 59 procedures, 49 (83.1%) achieved improvement but 10 could not on the postoperative excretory pyelogram and/or TcDTPA renogram. Three procedures (5.5%) required blood transfusion. Retroperitoneal leakage of the perfusate was observed in 3 procedures (5.0%). No other severe complications were observed. These results indicate that this procedure may be used for the reconstructive surgery in obstructive diseases of the upper urinary tract such as the ureteropelvic junction and the proximal 1/3 ureter. PMID- 2232418 TI - [Simultaneous occurrence of renal cell and transitional cell carcinoma in the same kidney and ureter. A case report]. AB - An unusual case of 2 concurrent primary renal tumors within the same kidney is reported. A 70-year-old woman presented with gross hematuria when she was in the hospital for cerebral infarction. Excretory urography revealed a marked expansion of the right kidney with no renal function. CT scan showed a mass arising from the right kidney, the hydronephrotic right renal pelvis, and a mass in the lower right ureter. Selective renal angiogram showed marked neovascularity of the mass. There was an encasement of the intrarenal artery to the lower pole. Angiographic findings were highly suggestive of a renal cell carcinoma with a second neoplasm in the renal pelvis. Subsequently, the patient underwent right radical nephroureterectomy and partial cystectomy. Section of the removed specimen revealed a 4.0 X 3.8 cm solid tumor confined to the kidney in the upper pole and a transitional cell carcinoma arising from the renal pelvis. In addition, transitional cell carcinoma was present in the distal ureter. PMID- 2232419 TI - [A case of medullary sponge disease associated with horseshoe kidney]. AB - A 60-year-old man visited our hospital with complaints of micturition pain and interruption of urinary stream. X-ray examinations were performed, showing no bladder and urethral stone. However, KUB revealed bilateral multiple renal stones. Excretory urography showed a horseshoe kidney and a concentration of the contrast medium in the ectatic tubules at the pyramidal apices. Calculi were also located in these ectatic tubules. Thus, we considered that this was a very rare case of medullary sponge disease associated with horseshoe kidney. So far there has been no case report of medullary sponge disease with horseshoe kidney in our country. PMID- 2232420 TI - [Male infertility]. PMID- 2232421 TI - [Fluorescence microscopy of the absorption and disappearance of adriamycin through the bladder epithelium in the rat]. AB - The absorption and disappearance of adriamycin (ADM) through the bladder epithelium in the rat was investigated using a fluorescence microscope. In the absorption study in vitro, ADM permeated through the epithelium into the lamina propria or the inner layer of the muscle within 15 minutes after instillation, showing no further infiltration into the deeper part of the bladder wall. In addition, fluorescence histological evidence for the uptake of ADM by the endothelial cells of the blood vessels in the lamina propria suggested a systemic diffusion of ADM to the whole blood by blood circulation. These data coincided well with the absorption study in vivo. On the other hand, ADM once absorbed in the bladder wall disappeared from the lamina propria or the inner layer of the muscle and was confined only in the epithelium at 60 min after the excretion of ADM. The intensity of ADM fluorescence then decreased gradually with time elapsed. No ADM fluorescence was recognized in the bladder tissue 48 hr later. In the absorption study with the BBN induced rat bladder tumor, ADM permeated into all the cells of papillary tumor within 5 minutes of instillation. The fluorescence histological method used in the present study is harmless and may readily be applicable to the pharmacodynamic study of ADM in human bladder tumors. This method proves to be a promising approach to the development of an ideal instillation therapy effective on bladder tumor cells without side-effects. PMID- 2232423 TI - [Neurogenic bladder in patients with lumbar vertebral disorders]. AB - Bladder and urethral functions were evaluated urodynamically in 114 patients with lumbar disorders including prolapsed lumbar intervertebral disc (66 patients), lumbar canal stenosis (19 patients), lumbar spondylolysis and/or spondylolisthesis (21 patients), lumbar spondylosis deformans (5 patients) and ossification of the yellow ligament of the lumbar spine (3 patients). The patients consisted of 88 males and 26 females with an average age of 47 years (range 17 to 73 years). Symptomatic organic infravesical obstruction was excluded by physical and radiographic examination. Cystometry revealed preoperative neurogenic bladder in 23 patients (20%); normal detrusor with overactive sphincter in 2 (9%), underactive in 8 (36%), overactive in 5 (23%) and equivocal in 7 (32%). One patient not receiving cystometry revealed abnormal uroflowmetry with 140 ml residual urine. Twenty of them underwent electromyographic examination of the external sphincter and 15 (75%) had an overactive sphincter. Nine (39%) of them complained no urological symptoms. Neurogenic bladder seemed to highly associate in those having abnormal tendon reflex in the lower extremities, decreased bulbocavernosus reflex and sensory disturbance in the perineal area, but there was no statistical significance. Of twenty-three neurogenic bladder patients, eighteen underwent a lumbar vertebral operation and fifteen received postoperative urodynamic evaluation. Uroflowmetry was improved in more than half of the patients within 3 months after the operation and cystometry was normalized in 4 of 7 patients who underwent cystometry over 6 months after the operation. Preoperative overactive detrusor remained unchanged in two of three patients who underwent cystometry over 6 months after the operation. PMID- 2232422 TI - [The analysis of prognostic factors for prostate cancer by multivariate analysis]. AB - Multivariable analysis (quantification method I and II) was used to investigate the relationship between survival rates and prognostic factors. The items studied were age, stage, pathological differentiation, gait disturbance, acid phosphatase and erythrocyte sedimentation rate (ESR). The data were available for 353 patients for all items. The significance of each item was evaluated in all patients-group, subgroup stratified by their cause of death, and subgroup stratified by their stage. The significance of age and gait disturbance which represent the general condition was proven in all patients, non-cancer death group and stage ABC group. In the cancer death group, stage D group was the most significant as prognostic factor. ESR was the most significant in the stage D group and the significance was gradually increased with the observation time. PMID- 2232424 TI - [A combined treatment with 8 MHz radiofrequency hyperthermia, HPC-adriamycin, immunotherapy, radiation, systemic chemotherapy and irradiation for invasive bladder carcinoma]. AB - Hyperthermia was induced for the treatment of invasive bladder carcinoma in order to study its usefulness. The subjects were 12 cases of invasive bladder cancer; including 5 cases of T2, 3 cases of T3, 2 cases of T4, and 2 cases of recurrence after total cystectomy. As previous treatment, 4 patients received radiotherapy and the other received TUR, systemic chemotherapy, and intravesical injection of anticancer drugs. For hyperthermia treatment, a Thermotron RF-8 was used for heating a deep seated tumor. Each case received hyperthermia 2 to 10 times. Combined therapy included injection of HPC-adriamycin into the urinary bladder in 5 cases, immunotherapy in 3 cases, M-VAC therapy in one case, radiotherapy in one case, radiotherapy and intra-arterial injection in one case, and Peplomycin and OK-432 local injection in one case. The treatment results showed a 75% effectiveness; with CR in 4 cases, PR in 5 cases, MR in 2 cases and PD in one case. Three patients died and 9 survived. Of four patients who had received radiotherapy as a previous treatment 3 cases obtained CR and one case MR. Therefore, it was considered that a favorable treatment effect with hyperthermia could be obtained after radiotherapy. PMID- 2232425 TI - [A study on cisplatin adsorbed to activated carbon particles as a new drug delivery system and its anti-cancer effect against human bladder cancer cell lines]. AB - Activated carbon characteristically shows an extremely high transmigration to the lymph node, as well as a sustained release of the adsorbed drugs. Therefore, several attempts to use activated carbon as a carrier in cancer chemotherapy have been done. In the present study, we first introduced a new drug-dosage form of cisplatin (CDDP) adsorbed to activated carbon particles (CDDP-CH), and examined its characteristics and anti-cancer effect against human bladder cancer cell lines. CDDP solution of varied concentrations (Randa) was mixed with activated carbon particles (Norit A) and examined for adsorption and discharge by atomic absorption spectrophotometry and high performance liquid chromatography. Total CDDP adsorption increased in proportion to the amount of activated carbon. CDDP CH was successfully prepared at an efficient concentration for cancer chemotherapy and CDDP-CH slowly discharged CDDP, indicating it as a useful means for the anti-cancer drug. Using cultured human bladder cancer cell lines (KU-1, HTB9), the anti-cancer effect was compared between CDDP and CDDP-CH by MTT-assay and double layer soft agar colony assay. CDDP-CH revealed an inhibitory effect against human bladder cancer cell lines. In view of the fact that activated carbon readily migrates to the lymph node, clinical application of this drug dosage form may be useful in cases of malignant tumor metastasis to the lymph node. PMID- 2232426 TI - [Suburethral sling procedure for urinary stress incontinence. With special reference to determination of tension of suspension from posturethrovesical angle measured by ultrasonography]. AB - Ten patients with urinary stress incontinence were treated by suburethral sling procedure using a polytetrafluoroethylene tube as the sling. The tension of suspension was determined by the post-urethrovesical angle measured by transrectal ultrasonography in each patient. In nine patients, the post urethrovesical angle ranged from 90 to 110 degrees, and urinary continence of the patients was completely obtained. The remaining one patient whose post urethrovesical angle was determined as 120 degrees could not obtain complete continence. None of the patients had subjective post-operative disturbance in urination and the peak flow rate of post-operative uroflowmetry hardly decreased in 7 patients in whom this was performed. Although post-urethrovesical angles reduced as the tension which suspended the bladder neck increased, the tension reforming the post-urethrovesical angle was various in each patient. Since one of the aims of suspension of the bladder neck for patients with stress incontinence is reform of the post-urethrovesical angles, correct and reasonable tension of suspension is to be obtained by measuring the post-urethrovesical angle. PMID- 2232427 TI - [Upper urinary tract tumors following bladder cancer]. AB - We treated in total 795 patients with primary transitional cell carcinoma of the urinary bladder between April, 1964 and December, 1988. Eighteen patients of them had upper urothelial cancer during the follow-up period. Thirteen of the 18 patients had received transurethral resection for the initial bladder cancer, while 3 total cystectomy and 2 segmental resection. The over-all incidence of bladder cancer patients who subsequently developed upper urinary tract tumors was 2.3 per cent. The interval between initial treatment of the bladder cancer and treatment for the upper urinary tract tumor ranged from 2 to 74 months (median 20 months). The five-year survival rate after treatment for the upper urinary tract tumor was 31.7 per cent. We conclude that the following are high risk patients for development of upper urinary tract recurrences: 1) patients with bladder cancer near orifices, 2) patients with recurrent bladder cancer under bladder preserving treatment for a long time, 3) patients with G2 multifocal bladder cancer. PMID- 2232428 TI - [The clinical efficacy of outpatient extracorporeal shock wave lithotripsy]. AB - From March 1989 through December 1989, 123 patients, 9 to 78 years old, were treated by extracorporeal shock wave lithotripsy (ESWL) with the Wolf Piezolith device. Outpatient treatment was performed routinely. Anesthesia was not required in all of the patients. No analgesia or sedation was given routinely. When pyuria had been found before treatment, a course of prophylactic oral antibiotics was given. Treatment consisted of 2000 to 6000 shocks in adults. The need for re treatment was decided on the basis of the follow up X-rays. Fragmentation into particles 5 mm in size or less occurred in 144 of the 149 renoureteral units (96.6%). Unfragmented stones were treated successfully by the combination therapy of ESWL and fiberoptic transurethral nephroureterolithotripsy (f-TUL). Of 144 renoureteral units, 3-month follow-up data are available for 96. Among the 96 units, the rate of being free of stones was 67 per cent for renal stones and 96 per cent for ureteral stones treated in situ. The over-all rate of being free of stones was 80.2 per cent. There were no significant complications. Ultrasound imaging has proved to be as effective as X-ray imaging. Outpatient ESWL with the Wolf Piezolith device is considered to be safe and efficient for the initial treatment of urinary stones. On the other hand, ESWL monotherapy is not sufficient for the treatment of complete staghorn calculi or long-term impacted ureteral calculi. We think that the combination use of ESWL and f-TUL is the most effective procedure for treatment of complicated stones. PMID- 2232429 TI - [Clinical studies on thirty-two cases of childhood urolithiasis]. AB - We evaluated 32 patients with urinary calculi under 16 years of age over the past 14 years since the founding of the Department of Urology, Kinki University School of Medicine. They comprised 0.8% of the total urolithiasis patients. They consisted of 18 boys and 14 girls with a male-to-female ratio of 1.29. The average age was 8.7 years for boys and 10.4 years for girls without any marked peak. The most frequently chief complaint was hematuria which was present in 15 cases (47%). Although pyuria was seen in seven cases (22%), urinary bacterial culture was positive only in 5. The underlying diseases could be diagnosed in 13 cases (41%), of which eight cases (62%) developed metabolic disorder. The sites of calculi were determined in 29 cases (91%), of which 28 had stones in the upper urinary tract. Surgical treatment was performed on 16 cases in 17 sessions. Ureterolithotomy was done in as many as five cases, followed by pyeloplasty in four cases. Nephrectomy was performed in only one case. There was only one case which had been treated with extracorporeal shock-wave lithotripsy (ESWL). The composition of calculi was found in 21 cases (66%), the majority or 13 cases (57%) of which had calcium-containing stones. Nevertheless, there was no case of hypercalciuria. When compared to the previous reports in Japan, it was worthy of note that calculi in the upper urinary tract and calcium-containing stones had higher incidences. It is expected that more patients will be treated with ESWL in the future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232431 TI - [Chromosome analysis of renal cell carcinoma]. AB - Of 8 tumors surgically extirpated from 8 patients with renal cell carcinoma, 7 were successfully processed in short-term culture by collagenase method, and 130 metaphases were extracted from these 7 tumors and were subjected to chromosomal analysis according to the G banding technique. As for karyotype, 4, 2 and 1 cases were mainly diploid, hypodiploid and aneuploid, respectively. The highest incidence of chromosome aberration was marked by #3 chromosome (5 of 7 cases of which 4 and 1 showed monosomy as clonal aberration and trisomy as non-clonal aberration, respectively). The commonest gain of chromosome was noted for #7 trisomy (4 of 7 cases). Two cases had already had metastases at the time of surgery, each showing #7 trisomy. Marker chromosome was noted in 6 of 7 cases. Structural chromosome aberration had a lesser incidence compared with numerical aberration; only clonal aberrations were long-arm aberrations (2q+, 6q+) of #2 and #6 chromosomes. Short-arm aberrations (3p-, 8p-) of #3 and #8 chromosomes were noted in one case each. 3p deletion, which is reported to be predominant in the literature, was noted only in one case. This was observed in triploid cells. However, all of metaphases showing 2q+ and 6q+ had concomitant #3 monosomy, and excess portions of #2 and #6 chromosomes were in good agreement with the band pattern of #3 chromosomal long-arm. Therefore, translocation of 3q12-qter in #2 and #6 chromosomes is supposed to lead to 3p deletion. A similar mechanism seems to be involved in the formation of marker chromosomes, suggesting the involvement of deleted #3 chromosome in marker chromosomes. PMID- 2232430 TI - [Relation of tumor number to clinical course of superficial papillary bladder tumors]. AB - Clinical courses of 293 patients with superficial papillary bladder tumors were analysed on the basis of tumor number at the first presentation. The follow-up period ranged from 6 to 266 months with a median of 59 months. 171 patients (58%) had a single tumor, while 122 (42%) had multiple tumors. Those older than 60 years occupied 68% in the latter group and 51% in the former (p less than 0.01). High grade tumors were more frequent in the latter than the former (p less than 0.05). The five-year recurrence rate was 68% for the latter and 39% for the former single tumor group (p less than 0.01). Malignant progression was observed in 3.6% of patients with a single tumor and 13.4% of those with multiple tumors (p less than 0.01). The results would offer a theoretical background to the finding of a poor ten-year actuarial survival rate of 54% for multiple tumor group compared with 76% for the single tumor group (p less than 0.05). However, the rate of primary cancer death was similar in both groups. PMID- 2232432 TI - [Histological and flow cytometric analyses of carcinogenesis of rat prostate cancer]. AB - Histological and flow cytometry (FCM) analyses were performed of carcinogenesis of rat prostate cancer induced with N-Nitroso-N-methylurea (NMU). Ten-week-old rats were inoculated intravenously (i.v.) with twice injections of NMU (30 mg/kg body weight) and then, divided into 3 groups; Group 1: the rats were injected subcutaneously with LH-RH analogue (100 micrograms/kg b.w.) every 4 weeks. Group 2: the rats were injected subcutaneously with testosterone enanthate (10 mg/body) every 2 weeks and Group 3: the rats were untreated to serve as controls. We further divided Groups 1 and 2 into (+) and (-) subgroups at 34 weeks after initial injection. Group 1 (+) or 2 (+) rats were continuously given the drug and in Group 1 (-) or 2 (-) rats the drug was suspended. At 44 or 53 weeks after initial injection, we removed the prostate and seminal vesicles of all rats and performed histological and FCM analyses of them. Histological analysis of rat prostates revealed hyperplasia in each group, and both Groups 2 (+) and 2 (-) showed an incidence as high as 87.5%. Atypical hyperplasia was sometimes observed in each group and its incidence was not significantly different between any 2 groups. At 51 weeks after initial injection, a macroscopic adenocarcinoma (weighing about 11 g) was found in the prostate of a dead rat of Group 2 (+). Histological analysis of rat seminal vesicles revealed hyperplasia in each group, in particular in Groups 2 (+) and 2 (-). In these groups all rats showed hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232433 TI - [Preoperative adjuvant therapy for urinary bladder cancer--preoperative intra arterial anticancer drugs infusion using artificial liver, and preoperative radiotherapy]. AB - One hundred patients with carcinoma of the urinary bladder were treated with preoperative intra-arterial anticancer drug infusion in combination with an active carbon-based artificial liver or preoperative radiotherapy (400 rad X 5 days, total 2000 rad) in order to alleviate systemic side effects after preoperative adjuvant therapy and to perform radical cystectomy as soon as possible. Five-year survival was 69.8% in the artificial liver combined preoperative intra-arterial anticancer drug infusion group, and that of the no pretreatment group and the preoperative irradiated group was 48.6% and 45.8%, respectively. In particular, the CDDP treated group had a higher 5-year survival of 77.4% than did the without CDDP treated group. This was attributable mostly to improved prognosis of T2, whereas either of these preoperative adjuvant therapies failed to ameliorate the prognosis of T3 or T4 stage patients. Therefore, systemic preoperative anticancer chemotherapies such as M-VAC are necessary to destroy "micrometastases" and to improve the prognosis of highly advanced bladder cancer. PMID- 2232434 TI - [Adverse reactions of antituberculous agents, especially about its onset and duration]. AB - We examined the adverse reactions of the antituberculous agents in 225 hospitalized patients (150: male, 75: female, average age: 45.4 years old) and the results were summarized as follows: 1) The side effects were seen in 53 patients (23.6%), and the abnormal laboratory findings were observed in 94 patients (41.8%). 2) The incidence of adverse reactions in patients treated with three drugs (INH, RFP, EB) and four drugs (plus SM) were 45.9% and 82.4%, respectively. 3) Adverse reaction appeared within one month after starting treatment in 67.9% of eligible patients, and it disappeared within one month from its onset in 76.8% of patients. There results suggested the importance of careful clinical observation especially soon after starting antituberculous therapy. PMID- 2232435 TI - [The significance of pleural fluid cytology in the differential diagnosis of pleurisy showing lymphocyte-predominant pleural effusion]. AB - We examined the significance of pleural fluid cytology in differentiation between tuberculous and non-tuberculous pleurisy in patients with lymphocyte-predominant pleural effusion. We divided pleural fluid cytologic findings into two patterns, that is "tuberculous" and "non-tuberculous pattern", according to the report by Spieler, and compared the cytologic pattern with the final clinical diagnosis. Thirteen out of 19 cases (68.4%) with tuberculous pleurisy showed "tuberculous pattern" in the pleural fluid cytology, while four (pleurisy associated with collagen-vascular disease, asbestosis and carcinoma, and idiopathic pleurisy) out of 13 (30.8%) with non-tuberculous pleurisy revealed "tuberculous pattern". The pleural fluid cytology could be used as one of the additional means to differentiate between tuberculous and non-tuberculous pleurisy, though it is impossible to differentiate between them with the pleural fluid cytology alone. PMID- 2232436 TI - [Effect of atypical mycobacterial infection on the cell-mediated immunity induced by Mycobacterium bovis BCG in mice. I. Suppression of delayed-type hypersensitivity]. AB - Mycobacterium avium Mino grows well in the lung, spleen or liver of susceptible mice, such as C57BL/6, C57BL/10, and B10 congenics. Infection with Mino inhibited the induction of delayed-type hypersensitivity (DTH) to BCG in the mouse receiving subcutaneous injection of BCG 2 weeks later. Post-infection with Mino did not affect DTH to BCG already established. Preceding infection with avirulent strains of atypical mycobacteria weakly suppressed the induction of DTH by BCG. On the other hand, Mino infection did not affect DTH to SRBC. DTH to Mino and DTH to BCG detected by PPD-I and PPDs hardly showed cross-reactivity. These results suggest that tuberculin skin reaction after BCG vaccination could be suppressed by the infection with atypical mycobacteria in humans, especially where these bacterial infections are prevailing. PMID- 2232437 TI - [Four cases of simultaneous discovery of familial tuberculous infection]. AB - Index case is a 17-year-old boy who was admitted to our hospital with pleurisy and a minimal pulmonary lesion, and tubercle bacilli were recovered from pleural fluid. A diagnosis of primary tuberculosis was made based on the onset by pleurisy and the existence of hilar and mediastinal lymph node swelling. On the same day, a 76-year-old man, grandfather of the index case was admitted for precise examination of suspected extensive pneumonia. Tubercle bacilli were also isolated from the pus of infected bulla obtained by puncture. Neither of these two cases, however, seemed to be the source of the familial tuberculous infection because of such sudden onset of the disease as pleurisy and pneumonia. Two months later, a 46-year-old man, father of the index case was examined at our hospital. He was considered to be the source of the familial infection because he was diagnosed as tuberculosis with positive smear and a thick wall cavity (3.2 cm in diameter) on the left apex, and abnormal shadow was detected on his chest X-ray already two years ago. The fourth case was a mother of the index case, and wife of the third case, whose chest radiography revealed an infiltrative shadow on the right apex by a family contacts examination. Though tubercle bacilli were not isolated from her sputum, pulmonary lesions considered to be tuberculosis due to their typical location and nature, a positive PPD skin test, and the response to antituberculous drugs. PMID- 2232438 TI - [Clinical immunology of tuberculosis]. AB - The standard tuberculin skin test has been known as the prototype of delayed type hypersensitivity testing which is mediated by T cells and macrophages and plays an important role in the pathogenesis of tuberculosis. Tuberculosis is indeed a chronic infectious disease, but variation in the host immune responses to tubercle bacilli results in the various clinical manifestations of the disease ranging from an immunologically hyperreactive state observed in pleural fluid lymphocytes in tuberculous pleurisy to an almost totally unresponsive state observed in those severely ill with refractory tuberculosis. In tuberculous pleurisy, T cells in pleural fluid respond remarkably in vitro to PPD tuberculin whereas T cells in peripheral blood responded poorly to PPD stimulation. Compartmentalization of PPD-reactive T cells in the pleural fluid and immunosuppression by T cells and/or macrophages in the peripheral blood were responsible for this immunological difference observed between the lymphocytes in pleural fluid and those in peripheral blood of tuberculous pleurisy. In advanced, drug-resistant tuberculosis as well as in nontuberculous mycobacterial infection, the proliferative responses of T cells in vitro to PPD stimulation were impaired. This depressed T cell response was due to depressed interleukin-2 (IL-2) production and not due to depressed IL-2 responsiveness. Therefore, the addition of exogenous IL-2, returned the depressed PPD-induced lymphocyte proliferation in vitro in these patients to the level of the response observed in lymphocytes from patients with newly-diagnosed tuberculosis. Our results suggest that recombinant IL-2 offers a novel approach to the therapy of advanced, drug-resistant tuberculosis and nontuberculous mycobacterial infection. Preliminary clinical trials of immunotherapy with recombinant IL-2 reveals the effectiveness of this therapy and encourages us to extend the trial to a larger scale. Tubercle bacilli have various biological activities. Research on tuberculosis and tubercle bacilli have contributed much to the progress of biochemistry, pathology and immunology. Mycobacterium is a fascinating organism, which now presents another big appeal to those studying immunology: Study of immunological interaction between gamma delta T cells and the highly conserved protein in mycobacteria, HSP, heat shock protein will contribute to the elucidation of the mechanism of immunological surveillance and the mechanism of autoimmune diseases. In addition, it will also contribute to the development of a new mycobacterial vaccine which will give direct, protective immunity against tuberculosis. PMID- 2232439 TI - [Development of a scale to measure the self concept of cesarean section mothers]. AB - Recently, the rate of cesarean section in Korea has been increasing. The results of several previous studies in foreign countries on the emotional responses of cesarean section mothers showed that they might experience difficulties in the mother-infant interaction due to fatigue, lack of early mother-infant interaction, disappointments, anger, feelings of loss of control, and other factors. Human behavior is said to be determined by one's self concept, and self concept is influenced by both internal and external environmental factors. A scale to measure the self concept of cesarean section mothers was needed in order to identify those who might have difficulties in the mother-infant interactions in future. The purposes of this study were to develop a measuring scale, and to test its reliability and validity. The process of this study was as follows. A structured interview was done with 50 cesarean section and vaginal delivery mothers to find their state of emotional reaction after giving birth to their babies. Based on the results of the interviews, a 50 items Likert scale was developed. The self concept of 268 cesarean section and vaginal delivery mothers who were hospitalized at six hospital in seoul were measured, during the period between Feb. 1 and April 30. Reviewing the discriminating power of each item by means of crosstabulation, ten items were selected for the final scale. The reliability and validity of this ten item scale were tested by Cronbach's alpha and t-test, using spss pc + package. The results of this study and recommendation are as follows. 1. The ten selected items were as follows. I feel pains in my breast. (-) I have a good appetite now. (+) I feel pains in my flank. (-) I feel fine now. (+) My body seems to have returned to its prepregnant state. (+) Thinking of the delivery process, I feel sorry. (-) I want to hold my baby in my arms. (+) I want to keep my own life, even if I became a mother. (-) I want to delegate the care of the baby to my mother/mother in law. (-) I think baby is my alter ege. (+) 2. The reliability of this scale was tested by Cronbach's alpha, and the coefficient of this scale was .8066. 3. The construct validity of this scale was tested by means of known group methods. The value of self concept for cesarean section mother was significantly lower than for vaginal delivery mothers (t = -5.51, df = 266, p = 0.007).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2232440 TI - [A study on autistic children in Korea]. AB - This Study was to determine the trend of child rearing attitude, to investigate how variables affect the child rearing attitudes, and to suggest directions for developing much needed parental effective training programs or counselling for autistic child in community. The subjects were seventy six mother's of autistic children who attending to 13 treatment institutions in Korea. The data were collected from 1, March to 30, May, 1985. Maternal Behavior Research Instrument exploited by Schaefer, used as a tool in this study. The research findings obtained were as follows: 1. Mothers, in general, had affective, restrictive attitudes, and were found to be affective, yet did not give a positive evaluation of children's behavior and used fear control extensively, thus made their children dependent. 2. There were no significant differences in child rearing attitude by children's sex and age. 3. There were no significant differences in child rearing attitudes by mother's age, education level and religion. 4. There was no significant difference in child rearing attitudes by father's occupation. PMID- 2232441 TI - [Primaparas' perceptions of their delivery experience and their maternal-infant interactions: compared according to delivery method]. AB - One of the important tasks for new parents, especially mothers, is to establish warm, mutually affirming interpersonal relationships with the new baby in the family, with the purpose of promoting the healthy development of the child and the wellbeing of the whole family. Nurses assess the quality of the behavioral characteristics of the maternal-infant interaction. This study examined the relationships between primiparas perceptions of their delivery experience and their maternal infant interaction. It compared to delivery experience of mothers having a normal vaginal delivery with those having a cesarean section. The purpose was to explore the relationships between the mother's perceptions of her delivery experience with her maternal infant interaction. The aim was to contribute to the development of theoretical understanding on which to base care toward promoting the quality of maternal-infant interaction. Data were collected directly by the investigator and a trained associate from Dec. 1, 1987 to March 8, 1988. Subjects were a random sample of 62 mothers, 32 who had a normal vaginal delivery and 30 who had a non-elective cesarean section (but without other perinatal complications) at three general hospitals in Seoul. Instruments used were the Stainton Parent-infant Interaction Scale (1981) and the Marut and Mercer Perception of Birth Scale (1979). The first observations were made in the delivery room (for vaginally delivered mothers only), followed by day 1, day 2, day 3, and 2 weeks, 4 weeks, 6 weeks and 8 weeks after birth, for a total of 7-8 contacts (Cesarean section mothers were observed on days 4 and 5 but the data not used for analysis). Observations in the hospital were made during the hour prior to scheduled feedings. The infant was placed beside the mother. Later contacts were made at home. Data analysis was done by computer using as SPSS program and included X2 test, paired t-test, t-test, and Pearson Correlation coefficient: the results were as follows. 1. Mothers who had a normal vaginal delivery tended to perceive the delivery experience more positively than cesarean section mothers (p = 0.002). The finding supported the hypothesis I that perception of delivery would vary according to the method of delivery. Mother's perceptions of birth were classified into three dimensions, labor, delivery and the baby. There was a significantly different and positive perception by the vaginally delivered mothers to the delivery experience (p = 0.000) but no differences for labor or the baby according to the delivery method (p = 0.096, p = 0.389).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2232442 TI - [Effect of individual patient teaching through home visiting on compliance with sick role behavior in diabetic patients and duration of the effect of the teaching]. AB - In order to determine the effect of individual patient teaching through home visiting on compliance with sick role behavior and the blood sugar level in diabetic patients, to determine if the effectiveness of the education was still present four years later and to inquire as to the effective time for a repeat education program this study was done through two quasi-experimental researches. The subjects consisted of 52 diabetic patients. The results of the study may be summarized as follows: 1. Hypothesis I, in which the compliance with sick role behavior, the knowledge on diabetes and the health belief of the experimental group who received a diabetic education program will be higher than those of the control group who didn't receive the diabetic education, was supported by both studies in 1984 and 1988, confirming the effect on diabetic patients of the individualized education through home visiting: In the 1984 study: Compliance(t = -11.7, p less than .001) Knowledge(t = -5.41, p less than .001) Health belief(t = -4.74, p less than .001) In the 1988 study: Compliance(t = -4.85, p less than .001) Knowledge(t = -2.85, p less than .01) Health Belief(t = -2.99, p less than .005) 2. The Hypothesis II, the blood sugar level of the experimental group will be lower than that of the control, was rejected in both studies, 1984 and 1988. 3. The Hypothesis III, the compliance, knowledge and health belief of the experimental group who received the education program in 1984 will not last till 1988, was supported in part, in compliance and health belief, but not in knowledge. In conclusion those who received the education program twice with an interval of 2 weeks, 4 years ago still had knowledge of diabetes but compliance and health belief had disappeared. PMID- 2232443 TI - [A study on the relationships of discomfort, self-esteem, personality and life satisfaction in persons with rheumatoid arthritis]. AB - The purpose of this study was to investigate the correlation of discomfort, self esteem, personality and life-satisfaction in persons with rheumatoid arthritis and to provide basic data to help them attain a better quality of life. From Jan. 27 to Feb. 24, 1988, 53 patients, registered at a rheumatic clinic at one general hospital in Seoul, were accepted as subjects for this study. The instruments used for this study were a discomfort scale and life-satisfaction scale developed by the researcher, Rosenberg's Self-esteem Scale and Wallston and Wallston's Multidimensional Health Locus of Control (MEILC) Scale. The reliability of the scales were tested by Cronsbach's alpha. The collected data were analyzed by the SAS program using unpaired t-test, ANOVA, and Pearson's Correlation Coefficients. The results were as follows: 1. There was a significant difference in the subjects perceived discomfort level (t = -3.49, p = .0010) between the onset of the disease (14.87 +/- 9.02) and the present (19.87 +/- 8.44). 2. There was a significant correlation between the MHLC-internal score and the MHLC-chance score (r = -.4366, p = .0011). 3. The findings related to the demographic variables regarding the MHLC scores were as follows: 1) Regarding sex, there was a significant difference for the MHLC-internal score (t = 4.2572, df = 15.2, p = .0007) between male (32.13 +/- 2.47) and female (27.56 +/- 4.17). But the MHLC chance score for male (15.13 +/- 2.85) was lower (t = 3.153 9, df = 21.8, p = .0047) than for female (19.47 +/- 6.29). 2) Regarding educational background, the MHLC-chance score for the below-high school group (20.52 +/- 5.81) was higher (t = 2.5450, df = 51.0, p = .0140) than the college graduate group (16.41 +/- 5.76). 4. The average Self-esteem score was 26.87 (S.D. = 5.29) and there was a significant correlation between the Self-esteem score and the MHLC-chance score (r = .3122, p = .0026). 5. It was found that the subjects' Discomfort score was correlated with the Self-esteem score (r = -.3788, p = .0051) and the Life satisfaction score (r = -.3570, p = .0087). It was also found that subjects' Self esteem score was correlated with the Life-satisfaction score (r = .4474, p = .0008). PMID- 2232445 TI - [Influence of stress experience on change of attention]. AB - For a man to maintain attention, he needs to keep a certain level of arousal. An inordinate increase or decrease in the level of arousal eventually has a negative influence on attention. Precedent research has shown that the degree of attention changes when an experience of stress is related to anxiety resulting in a rise in arousal. This research was done to examine this hypothesis by looking at the 27 female students, 14 of whom had failed in the annual examination. The results of the investigation are as follows: The stress of failure in the examination was seen to raise the level of physiological arousal. Although pulse and electromyography showed no significant change, further inquiries should be made based on other types of methodology. In spite of the rise of arousal, the performance of selective task was degraded. This suggests those students failed to give moderate attention to given information for that kind of task. But the exact reason of that failure was not identified: that is it was difficult decide whether they gave too much attention to the anxiety brought about by stress. Performance of integral tasks, however, did not show any degradation. Judging from these results, stress seems to exert significant influence on attention in the selection of the appropriate information among the various options given. This offers an important hint in relation to the health care situation where nursing information is offered. Clients who receive nursing information in stressful situations may have difficulty in separating and selecting this helpful information from other options which they have acquired through their life experience. The content and terminology of nursing information may be strange and unintelligible to clients, although they are quite familiar and distinct to nurses. So, it is desirable for nurses to give, in addition and at the same time when nursing information is given, some certain related information as devices for selection, instead of merely giving nursing informations as such. So far it is not clear whether the concepts of information processing theory can be suitably applied to nursing. However, it is obvious, according to this research, that the quality of attention is disturbed in the stress situation. This is why further inquiries should be made into attention in practical nursing situation. PMID- 2232444 TI - [The effect of EMG level by EMG biofeedback with progressive muscle relaxation training on tension headache]. AB - The purpose of this study is to assess if EMG biofeedback training with progressive muscle relaxation training is effective in reducing the EMG level in patients with tension headaches. This study which lasted from 23 October to 30 December 1989, was conducted on 10 females who were diagnosed as patients with tension headaches and selected from among volunteers at C. University in Seoul. The process of the study was as follows: First, before the treatment, the baseline was measured for two weeks and the level of EMG was measured five times in five minutes. And then EMG biofeedback training was used for six weeks, 12 sessions in all, and progressive muscle relaxation was done at home by audio tape over eight weeks. Each session was composed of a 5-minute baseline, two 5-minute EMG biofeedback training periods and a 5-minute self-control stage. Each stage was followed by a five minute rest period. So each session took a total of 40 minutes. The EMG level was measured by EMG biofeedback (Autogenic-Cyborg: M 130 EMG module). The results were as follows: 1. The average age of the subjects was 44.1 years and the average history of headache was 10.6 years (range: 6 months-20 years). 2. The level of EMG was lowest between the third and the fourth week of the training except in Cases I and IV. 3. The patients began to show a nonconciliatory attitude at the first session of the fifth week of the training. PMID- 2232446 TI - [An operations study on a home health nursing demonstration program for the patient discharged with chronic residual health care problems]. AB - The study was conceived in relation to a concern over the growing gap between the needs of chronic patients and the availability of care from the current health care system in Korea. Patients with agonizing chronic pain, discomfort, despair and disability are left with helplessly unprepared families with little help from the acute care oriented health care system after discharge from hospital. There is a great need for the development of an alternative means of quality care that is economically feasible and culturally adaptable to our society. Thus, the study was designed to demonstrate the effectiveness of home health care as an alternative to bridge the existing gap between the patients' needs and the current practice of health care. The study specifically purports to test the effects of home care on health expenditure, readmission, job retention, compliance to health care regime, general conditions, complications, and self care knowledge and practices. The study was guided by the operations research method advocated by the Primary Health Care Operations Research Institute (PRICOR) which constitutes 3 stages of research: namely, problem analysis solution development, and solution validation. The first step in the operations research was field preparation to develop the necessary consensus and cooperation. This was done through the formation of a consulting body at the hospital and a steering committee among the researchers. For the stage of problem analysis, the Annual Report of Seoul National University Hospital and the patients records for last 5 years were reviewed and selective patient interviews were conducted to find out the magnitude of chronic health problems and areas of unmect health care needs to finally decide on the kinds of health problems to study. On the basis of problem analysis, the solution development stage was devoted to home care program development asa solution alternative. Assessment tools, teaching guidelines and care protocols were developed and tested for their validity. The final stage was the stage of experimentation and evaluation. Patients with liver diseases, hemiplegic and diabetic conditions were selected as study samples. Discharge evaluation, follow up home care, measurement and evaluation were carried out according to the protocols of care and measurement plan for each patient for the period of 6 months after discharge. The study was carried out for the period from Jan. 1987 to Dec. 1989. The following are the results of the study presented according to the hypotheses set forth for the study; 1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2232447 TI - [A study of the ethical values of Korean nurses]. AB - The purpose of this study is to identify whether ethical values of Korean nurses are deontological or utilitarian. Nurse's ethical value questionnaire was developed from review of literature and interview of nurses in the clinical settings. Content validity was tested from three nursing faculties and staffs. Ethical problems are categorized into four areas: 1) human life area 2) nurse patient relationship area 3) nurse-nursing task relationship area 4) nurse colleague relationship area The data were obtained from the 404 nurses in the clinical settings from Feb. to Mar. in 1990 by ethical value questionnaire. The analysis of data was done by Pearson's correlation coefficient, t-test, anova. The results of this study were as follows: 1. The ethical values of human life slightly took up the position of utilitarian. 2. The ethical values of nurse patient relationships slightly took up deontological position. 3. The ethical values of nurse-nursing task relationships slightly took up deontological position. 4. The ethical values of nurse-colleague relationships greatly took up deontological position. 5. The ethics of nurses related to demographic characteristics of religion, attitude of nursing, ethical standards, education level and post. Those who have religion took up more deontological position than those who have not. Those who have positive attitude of nursing and firm ethical standards took up more deontological position than those who have not. Those who have higher education level and post took up more deontological position than those who have not. PMID- 2232448 TI - Future trends in nursing education. PMID- 2232449 TI - Computer-based video instruction in nursing: one nurse's experience as author. PMID- 2232451 TI - Kansas Newman College off-campus BSN program for R.N.'s. PMID- 2232450 TI - Converting the last diploma school in Kansas: a perpetual of caring. PMID- 2232452 TI - [Genetic aspects of systemic arterial hypertension]. PMID- 2232453 TI - [Comparative study of the hypotensive action of monotherapy using hydrochlorothiazide and its combination with triamterene and amiloride and their effect on hemodynamics at rest and during exercise therapy]. AB - A comparative study was undertaken to examine antihypertensive effects and impact of hydrochlorothiazide (HCT) alone or in combination with triamterene or amiloride on the hemodynamics of 79 patients with Stage II hypertension. With small doses, the resting recumbent systolic blood pressure was decreased to a significantly greater extent when the combinations (HCT + triamterene, in particular HCT + amiloride) were used than when the agent alone was given; diastolic blood pressure became lower only with a combination of HCT + amiloride than its monotherapy. When double doses were used, no potentiating antihypertensive action of potassium-sparing diuretics was ascertained. It was concluded that it was more preferable to use HCT in combination with diuretics, amiloride in particular, than as monotherapy. PMID- 2232454 TI - [Changes in lipid fractions of blood during the treatment of hypertension with prazosin and trasicor]. AB - The paper deals with the study into the benefits of prazosin and trasicor used in arterial hypertension. Their effects on the blood lipid composition were evaluated. With prazosin, the steady antihypertensive effect was reached in 81.0%, whereas with trasicor, it was attained in 46%. When prazosin was given, total cholesterol and triglycerides were statistically significantly decreased by 6.8 and 14.8%, respectively, while high density lipoproteins was increased by 9.1%. When trasicor was administered, no changes were observed in the spectrum of serum lipids. Thus, prazosin is effective in correcting two major risk factors for coronary heart disease, namely arterial hypertension and hyperlipoproteinemia, thereby reducing a risk for coronary heart disease. PMID- 2232455 TI - [Changes in various biophysical parameters of blood circulation during physical exertion in patients with a mild form of hypertension]. AB - Sixty four patients (mean age, 46 +/- 3.1 years) with mild hypertensive disease (MHD) were examined. The diastolic pressure recorded in MHD patients in the control period ranged from 95 to 104 mm Hg. There was no evidence of left ventricular hypertrophy (LVH) in 46 patients, whereas 16 had significant signs of LHN. MHD patients without LVH signs showed regularly increased cardiac mechanical performance and its static component through slightly diminished propulsive performance of the myocardium. As moderate LVH evolved in MHD patients, a reduction in kinetic energy of cardiac output was observed, which tended to decrease the static component of mechanical work of the heart, which suggested that the adaptive response of the circulatory system was impaired to some extent. PMID- 2232456 TI - [Characteristics of peripheral circulation and tissue metabolism in patients with functional venous hypertension and various forms of arterial hypertension]. AB - Venous-occlusion plethysmography was used to examine peripheral hemodynamics. Oxygen transport, serum lactate and pyruvate levels, and ++intra-tissue pressure in the forearm muscles were studied. A total hypoxemic test was employed as a functional tool. The findings suggest that the changes in venous blood flow and tone, transcapillary and tissue metabolism are unidirectional in functional venous hypertension, borderline hypertension, and hypertensive disease, which should be taken into account in the diagnosis and treatment. PMID- 2232457 TI - [Regulation of calcium metabolism in hypertension]. AB - In patients with hypertensive disease, the intravenous calcium tolerance test revealed a delayed elimination of loading hypercalcemia, which totally reflects the effectiveness mechanisms aimed at removing excessive calcium from the extracellular space. In hypertensives, renal calcium excretion was also delayed due to a lower suppression of calcium channel reabsorption. The patients showed a greater background concentration of parathyroid hormone (PTH) and during the calcium tolerance test a much lower PTH levels and higher calcitonin concentrations, though their homeostatic effects remained inadequate due to their diminished sensitivity of target organs. Thus, there was an increase in the activity of parathyroidal glands in patients with hypertensive disease. PMID- 2232458 TI - [Use of autologous pericardium in plastic surgery of the right coronary artery in patients with ischemic heart disease]. AB - The paper describes the procedure developed by the authors for surgical myocardial revascularization in patients with coronary heart disease (CHD) via direct reconstruction of the ostium and all the segments of the right coronary artery by performing direct endarterectomy and subsequent plasty with free autopericardial flaps. The findings indicate that this surgical method is beneficial for CHD patients. In some cases, it may be the method of choice in the surgical treatment of CHD patients. PMID- 2232459 TI - [Work capacity of patients with ischemic heart disease after aortocoronary bypass]. AB - A comparison was made of the clinicofunctional efficiency and social significance of surgical therapy techniques in patients with coronary heart disease (CHD). One hundred and seventy eight patients aged 25 to 59 years who had been operated on in the A. N. Bakulev Institute of Cardiovascular Surgery from 1984 to 1987 were examined. In prolonged periods (mean 2.8 +/- 0.2 years) following surgeries, 85.6% of the patients showed clinical improvement as compared to the preoperative period. At the same time, a total of 43.3% of the patients returned to work, the figure being much less than that observed in the preoperative period. (78.1%). Following the surgery, there was a high rate (94.4%) of disability. Two groups of factors were defined, which determined the patients' return to work after coronary aorta bypass grafting. The low work resumption and high disability rates after surgery are due to the lack of a national social rehabilitation programme for this group of patients. PMID- 2232460 TI - [Clinical evaluation of transient myocardial ischemia]. AB - Out of 432 patients with coronary heart disease, 106 (24.5%) were found to have transient myocardial infarction during ECG monitoring of ST segment for 10 hours of daily activity. High-grade ventricular arrhythmias were revealed in 74.6% of mainly male and middle-aged subjects. 63.4% of the patients exhibited congestive heart failure, 48.1% had postinfarct cardiosclerosis, and 25.5% presented with diabetes mellitus. Transient myocardial ischemia was more frequently detected during exercise and more rarely during emotional stress (21.7%), meal (19.8%), and smoking (7.8%). Asymptomatic episodes of ST segment elevation were recorded in 36.8%, while asymptomatic episodes of ST segment depression, in 29.2%. The duration of asymptomatic episodes of ST segment elevation and depression was twice and 1.5 times, respectively, less than that of symptomatic ones. Substantial myocardial perfusion and metabolic impairments were revealed with an asymptomatic ST segment depression frequency of at least one an hour, an amplitude of more than 2 mm, and a duration of no less than 40 min. PMID- 2232461 TI - [Study of metabolic characteristics in patients with ischemic heart disease based on the insulin test]. AB - The study was undertaken to examine 68 healthy males and 34 patients with Functional Class I coronary heart disease. The insulin test (fasting intravenous simple insulin, 0.15 U/kg body weight, was given in the morning) was performed. The study was conducted in 3 stages: 1) before, 2) 30 min, and 3) 2 hr after insulin administration. Examination of glycemia and gas exchange revealed changes resulting in impaired energy supply of the body in CHD. In CHD patients, the enhanced glucose uptake after insulin was followed by abnormalities both in aerobic and anaerobic glucose oxidation. The insulin test detected the signs of excessive overtension and diminished reserve potentialities of the sympathetic adrenal system early in CHD. PMID- 2232462 TI - [Various indicators of vascular-thrombocytic hemostasis and blood rheology in ergometrine tests]. AB - The function of platelets and erythrocytes and content of Willebrand's factor in the plasma from 45 patients with exercise-induced or spontaneous angina pectoris were examined before and after ergometrine, 0.1 mg. The patients with a negative ergometrine response showed a lower platelet sensitivity to all the aggregation inductors used in vitro, spontaneous platelet aggregation being absent. The function of erythrocytes and plasma levels of Willebrand's factor remained unchanged. The patients with a significant ischemic response to ergometrine exhibited platelet activation attended by the release of granule contents and formation of blood circulating platelet microaggregates. Concurrently, there was a decrease in erythrocyte deformability, as well as spontaneous blood red cell aggregation, the plasma levels of Willebrand's factor were increased 1.5-2-fold. PMID- 2232463 TI - [Treatment of patients with arterial hypertension and the ways of its optimal management (results of long-term and controlled therapy)]. PMID- 2232464 TI - [Antioxidant emoxipin: its effect on the formation of a necrotic focus and reparative processes in myocardial infarction]. AB - The effect of the water soluble antioxidant emoxipin given intravenously in a dose of 10 mg/kg for 5 days, then intramuscularly 1 mg/kg for 15 days. Comparison with the values found in the control group of patients with myocardial infarction revealed that emoxipin contributed to limitation of the size of a necrotic focus and accelerated reparative processes, whose result was a lower incidence of circulatory failure. One of the main mechanisms responsible for beneficial effects of emoxipin on the clinical course of myocardial infarction consists in normalization of lipid peroxidation and parameters of the antioxidative status. PMID- 2232465 TI - [Use of integral indicators of precordial mapping in differential diagnosis of focal-cicatricial lesions of the myocardium]. AB - The paper proposes new criteria for differential diagnosis of myocardial "focal scarring" and "++pseudo-scarring" changes in various cardiac abnormalities and homogeneous morphological alterations in the ventricular complex on ECG (the QS, Qr-type abnormalities of the R line) by using the findings of 35 lead ECG mapping (PM-35). ECG-12 and PM-35 were analysed in 427 patients, including those with coronary heart disease (n-122), arterial hypertension and aortic malformations (n 130), dilated cardiomyopathy, congenital cardiac disease (n-175). Electrocardiographic signs of focal scarring lesions were revealed in all the cases with coronary heart disease and 66 with myocardial hypertrophy. The total value of ST segment depression and the sum of Q wave squares in three to five vertical mapping columns were found to be the most significant differential and diagnostic criterion. When scars and ++pseudo-scars were differentiated, a sensitivity of 75% was obtained at a specificity of 87%. PMID- 2232466 TI - [Diagnostic and prognostic value of quantitative indicators of 12 ECG leads in ischemic heart disease]. AB - The study was undertaken to examine 35 patients with chronic coronary heart disease and 20 patients with neurocirculatory dystonia concurrent with the cardialgic syndrome, the latter were enrolled into a control group. Detection of sigma R in the standard leads of resting ECG and at the peak of atrial pacing made it possible to single out groups of chronic coronary heart disease patients, which differed in clinical manifestations of the disease, myocardial contractility, hemodynamics, and myocardial lactate extraction. In patients with chronic coronary heart disease ti is recommended to use ECG measurements (sigma R and nST) in the standard leads during loading tests to give a comprehensive characterization of the pump function and the severity of myocardial ischemia, the prognosis of the natural history of the disease and risk for myocardial infarction. To enhance the sensitivity and specificity of loading tests, it is recommended to take into account higher sigma R in combination with ST segment depression when the results of the tests are assessed. PMID- 2232467 TI - [Neuro-psychological status and its role in the formation of adaptive compensatory reactions in patients with myocardial infarction]. AB - The course of adaptative and compensatory responses are associated not only with the extent of myocardial lesion, but with the status of ++psycho-autonomic regulation. Lack of true psychogenias and nervous and mental disorders, mainly the adrenomedullary pattern of sympathetic activation in the acute period of the disease contribute to stabilization of cardiovascular values and an uncomplicated course of myocardial infarction. On the contrary, asthenization of the ++neuro mental sphere due to premorbid conflict was accompanied largely by a noradrenaline++ sympathetic activation and reversible complications of myocardial infarction. Prolonged psychogenias and neurotic personality disadaptation promotes the development of depressive and hypochondriacal disorders in the acute period of the disease; these are followed mainly by parasympathetic autonomic responses and concurrent with severe myocardial infarction. PMID- 2232468 TI - [Radiocardiography and rheography of the pulmonary artery in the diagnosis of disorders of hemodynamics and right-ventricular contractility in patients with chronic obstructive bronchitis]. AB - Radiocardiography and rheography of the pulmonary artery were used to examine impairments in hemodynamics and contractile function of the right ventricle in 40 patients with chronic obstructive bronchitis complicated with persistent hypertension. Right ventricular hemodynamic and contractile impairments were shown to be not equivalent with similar clinical and functional signs of pulmonary hypertension. This fact indicates that the use of special techniques is of practical value in the determination of right ventricular hemodynamics and myocardial contractility in patients with chronic obstructive bronchitis. Radiocardiography and rheography of the pulmonary artery are sufficiently reliable noninvasive techniques for examining the hemodynamics and contractile function of the right ventricular myocardium. PMID- 2232469 TI - [Effect of the optimal dose of finoptin on various components of the circulatory system in heart failure in patients with ischemic heart disease]. AB - Following sublingual finoptin and following its course therapy, 27 patients with coronary heart disease in the presence of Stages I-IIA circulatory failure displayed positive central hemodynamic changes, myocardial contractile function improvement, afterload decrease, and a tendency to normalization of vascular and intravascular alterations. PMID- 2232470 TI - [Clinico-functional characteristics of patients with arteriosclerosis obliterans of the lower extremities and painless myocardial ischemia]. AB - During manually performed exercise, ECG revealed silent myocardial ischemia related ST segment depression in 62 patients with atherosclerosis obliterans in the lower limbs in the absence of evident signs of coronary abnormalities. The patients displayed decreased cardiac output, elevated total peripheral resistance, structural and functional alterations in the end blood flow system, and diminished exercise tolerance as compared to healthy subjects and atherosclerosis obliterans patients with negative loading tests. The aforementioned abnormalities were also revealed in subjects suffering from atherosclerosis obliterans in the lower limbs and documented coronary heart disease. PMID- 2232471 TI - [Pathophysiological and clinical evaluation of the effectiveness of dalargin in the treatment of arterial occlusive diseases of the lower extremities]. AB - Eighty seven patients with Stages II-III vascular occlusions in the lower extremities were examined. The clinical and biochemical parameters of the course of the disease were found to improve in the patients who received in earlier periods dalargin supplemented to the combined therapy than in those from a matched group. There was a decrease in femoral venous blood lactate concentrations in the diseased extremity, blood cholesterol and parathyroid hormone levels. The mechanisms responsible for effects of dalargin on metabolic parameters and clinical indices of the patients' condition were also discussed. Whether it is possible to use dalargin in the combined therapy for extremity vascular occlusive diseases is considered. PMID- 2232472 TI - [Plasma mineralocorticoids--aldosterone and desoxycorticosterone-- in patients with"low-renin"arterial hypertension]. AB - The plasma aldosterone (A) and desoxycorticosterone (DOCS) levels were measured in 10 patients with primary aldosteronism and in 2 subgroups with low-renin hypertensive disease (LRHD): (1) those with normal adrenal glands++ (n - 11) and (2) those with structural changes in the cortex (n - 11). The patients from Subgroup 1 showed the lowest basal A and DOCS levels (107.29 +/- 12.90 and 0.080 +/- 0.013 ng/ml, respectively) and low concentrations of the two hormones after stimulation of 4-hour walk (211.57 +/- 30.47 and 0.095 +/- 0.024 ng/mg, respectively). In the patients from Subgroup 2, the basal and 4-hour post-walk++ A and DOCS contents were increased in the cortex (basal 201.50 +/- 41.59 and 0.177 +/- 0.36 ng/mg and poststimulation 331.33 +/- 30.47 and 0.302 +/- 0.061 ng/ml, respectively). Some patients with primary aldosteronism displayed the same DOCS response to stimulation as did those with LRHD in the presence of structural cortical changes. Histological examination of operative biopsy specimens indicated that higher DOCS levels were associated with diffuse nodal hyperplasia of the zona fasciculata in the cortex. The results suggest that there may be a LRHD variant running with excessive DOCS secretion and related to pathogenetically related to hyperplasia of predominantly the zone fasciculata in the adrenal cortex. PMID- 2232473 TI - [Predicting congenital cardiovascular defects on the basis of their immunogenetic characteristics]. AB - The study was undertaken to examine 80 children with congenital heart and vessel malformations, their parents (50 married couples), and 100 families with healthy children. The antigen typing of the HLA system was accomplished by using the Terasaki microlymphocytotoxic test. A statistically significant correlation was found between B35 antigens and septal malformations, vascular diseases, and congenital cardiomyopathies. The unfavorable obstetric history was shown to play a role in the occurrence of developmental malformations. The data of an analysis of HLA antigens in the parents of the children with congenital malformations suggest that a marked HLA antigen compatibility of married couples is one of the cause of pregnancy complications and developmental malformations in their offspring. PMID- 2232474 TI - [A method of modeling of occlusion-reperfusion induced myocardial infarction and quantitative evaluation of the effectiveness of limitation of its size]. AB - An experimental mathematical model was proposed to assess the efficiency of experimental myocardial infarction (MI) size limitation. A canine model of occlusion-reperfusion myocardial lesion was used in an acute experiment with an open chest. 90-minute occlusion and 4-hour reperfusion were performed by carotid coronary bypass surgery. The necrotic zone and the risk area were visualized by double perfusion with tetrazolium staining. Retrograde coronary blood flow was used as a measure of collateral blood flow. The multiple linear regression equation with values of the risk zone and retrograde blood flow/risk area ratio used as independent variables enabled the size of myocardial infarction to be highly accurately predicted. Comparison of the true size of MI with the "expected" one provided methods for quantitative assessment of pharmacological limitation of MI sizes. Calculating an individual value for each animal made it possible to examine its relation to coronary circulation parameters and facilitated comparison of benefits from various agents. PMID- 2232475 TI - [Central, pulmonary and cerebral hemodynamics in various stages and hemodynamic variants of hypertension]. PMID- 2232476 TI - [Evaluation of hemodynamic changes after repeated trans-esophageal cardiac electric stimulation in the diagnosis of ischemic heart disease]. PMID- 2232477 TI - [Psychological reactions of patients with ischemic heart disease to aortocoronary bypass]. PMID- 2232478 TI - [Use of trans-esophageal cardiac electric stimulation in the evaluation of anti arrhythmia therapy in patients with paroxysms of atrial fibrillation and atrial flutter]. PMID- 2232479 TI - [Active detection of arrhythmia in patients with cardiac and extracardiac pathology]. PMID- 2232480 TI - Summary: Symposium on Lymphocyte Activation. PMID- 2232481 TI - Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules? PMID- 2232482 TI - Glomerular basement membrane degradation by endogenous cysteine proteinases in isolated rat glomeruli. AB - Recent in vitro and in vivo studies suggest that cysteine proteinases may play an important role in degradation of the glomerular basement membrane (GBM) by renal glomeruli. However, little information is available concerning the cysteine proteinases present in glomeruli, the distribution of cysteine proteinases in other areas of the kidney, or the potential role of endogenous glomerular cysteine proteinases in GBM degradation. Using well characterized fluorogenic substrates, we have documented the presence of the cysteine proteinases, cathepsins B, H, and L, in glomeruli (0.45 +/- 0.06, 0.39 +/- 0.05, and 0.66 +/- 0.14 mU/mg protein, mean +/- SEM, N = 8) and other fractions prepared from normal rat kidney. The presence of cysteine proteinases in glomeruli was verified by fluorescence microscopy. For each proteinase, the activity was: proportional to the amount of tissue protein and time of incubation; dependent on the presence of exogenously added dithiothreitol; and completely inhibited by the specific cysteine proteinase inhibitor, E-64. The pH optimum for cathepsin B (substrate: Z Arg-Arg-HNMec) and L (substrate: Z-Phe-Arg-HNMec in the presence of Z-Phe-Phe CHN2) was approximately pH 6.0 for both glomeruli and renal cortex; while that for cathepsin H (substrate: Arg-HNMec) was approximately 6.5. Incubation of sonicated glomeruli with 3H-GBM under conditions optimal for cysteine proteinase activity (pH 4.5, 1 mM EDTA, and 1 mM dithiothreitol, 37 degrees C) resulted in significant GBM degradation as measured by the release of non-sedimentable (10,000 x g, 10 min) radioactivity or hydroxyproline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232484 TI - Renin release from microdissected superficial, midcortical, and juxtamedullary afferent arterioles in rabbits. AB - Renal renin content and release decrease from outer to inner cortex; this may be due to a cortical-to-medullary gradient in glomerular density and/or renin content per afferent arteriole. Although low sodium diets have been reported to decrease the tissue renin gradient, little information is available on renin release by different areas of the renal cortex or the effect of a low sodium diet. In the present study, we examined basal- and isoproterenol-stimulated renin release and content in microdissected superficial, midcortical, and juxtamedullary afferent arterioles from rabbits on normal and low sodium diets. Renin content was 25.8 +/- 3.6, 1.4 +/- 0.32, and 0.27 +/- 0.09 ng angiotensin I (Ang I)/hour/arteriole in the superficial, midcortical and juxtamedullary arterioles, respectively. Dietary sodium restriction significantly increased it to 60.1 +/- 7.3, 13.8 +/- 3.1, and 1.48 +/- 0.6, respectively. Renin release was 0.64 +/- 0.13, 0.15 +/- 0.04, and 0.025 +/- 0.013 ng Ang I/hour/arteriole/hour incubation of arteriole in the superficial, midcortical and juxtamedullary arterioles, respectively. With sodium restriction it increased significantly for the superficial, (1.77 +/- 0.27) and midcortical (0.62 +/- 0.11) but not the juxtamedullary arterioles (0.038 +/- 0.02). With either diet, renin release and content among the three types of arterioles were significantly different. Isoproterenol (1.6 x 10(-4) M) significantly stimulated renin release from all three types of arterioles whether rabbits were fed a normal or low sodium diet; however, only in the superficial arterioles was the increase (delta) greater with dietary sodium restriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232483 TI - Effect of chronic respiratory acidosis on urinary calcium excretion in the dog. AB - It is currently believed that the two chronic acidemic disorders exert disparate effects on urinary calcium excretion: chronic metabolic acidosis induces consistent hypercalciuria, but no appreciable change or even a decrease in calcium excretion is reported to attend chronic respiratory acidosis. Whereas the effect of metabolic acidosis is well documented, little work has been carried out in chronic hypercapnia. In fact, most of the studies on chronic respiratory acidosis were short in duration, had employed only mild hypercapnia, or had failed to control carefully the prevailing metabolic conditions. We have carried out balance observations in nine dogs exposed to a 10% CO2 atmosphere in an environmental chamber for a period of two weeks. Chronic respiratory acidosis led to a significant increase in urinary calcium excretion from a mean control value of 0.4 +/- 0.1 mmol/day to 0.6 +/- 0.1 mmol/day during both week 1 and 2 of hypercapnia (P less than 0.05). Hypercalciuria occurred even though filtered load of calcium fell. Mean fractional excretion of calcium increased significantly during each week of hypercapnia averaging 0.60 +/- 0.12% during control, 1.05 +/- 0.13% during week 1, and 1.26 +/- 0.17% during week 2 of hypercapnic exposure (P less than 0.05). There were no changes in plasma levels of immunoreactive parathyroid hormone or 1,25-dihydroxyvitamin D3. These findings suggest that chronic respiratory acidosis, just like chronic metabolic acidosis, augments urinary calcium excretion by a direct depressive effect on the tubular reabsorption of calcium. PMID- 2232485 TI - Nephron function in the early phase of ischemic renal failure. Significance of erythrocyte trapping. AB - Trapping of red blood cells (RBCs) in renal medulla vasculature in postischemic acute renal failure (ARF) was found to depend upon the length of the ischemic period. Thus trapping occurred after 45 minutes but not 25 minutes of ischemia. By prior hemodilution to a hematocrit (hct) of 30%, RBC trapping after 45 minutes of ischemia could be completely prevented. Likewise hemo-concentration (hct = 60%) before 25 minutes of ischemia resulted in extensive RBC trapping. By increasing or decreasing the hct, the contribution of RBC trapping to the functional defects and decrease in renal blood flow that follows minor (25 min) and more substantial (45 min) ischemia was investigated. Renal blood flow (RBF) was measured by microspheres, and vascular and tubular pressure by the micropuncture technique. Glomerular filtration rate (GFR) was estimated from inulin clearance, and tubular function from urine osmolality and sodium and potassium excretion. It was found that postischemic RBF was not correlated to RBC trapping but depended on the length of ischemia. After both 25 and 45 minutes of ischemia tubular obstructions occurred in the proximal tubules and/or loops of Henle, causing an increase in proximal tubular pressure. These obstructions were dependent on the length of ischemia but not on RBC trapping. After hemoconcentration and 25 minutes of ischemia there was an increment in distal tubular pressure, indicating that abundant RBC trapping may contribute to an increase in tubular pressure by compression of medullary tubules and thereby reduce GFR. When the damage was more severe other factors came into play and the contribution of RBC trapping to the decrease in GFR was minimal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232486 TI - Effect of acute stimulation of renin secretion on renal renin content in vivo. AB - Acute stimulation of renal renin secretion has been reported to increase, not change, or decrease intra-renal renin (IRR) content. However, these effects and the potential mechanisms for acute changes in IRR content have not been studied directly. In this study, the effect of acute stimulation of renin secretion on IRR content was studied directly using a new in vivo blood perfused rabbit kidney preparation. Following removal of the right kidney for determination of IRR content (N = 7) the left kidney was cannulated and perfused for an average of 55 minutes (baseline) at mean arterial blood pressure. Renin secretion by the left kidney was subsequently stimulated by reducing renal perfusion pressure to 60 mm Hg and administering enalapril, 1 mg/kg intravenously. After 38 to 140 minutes (mean 90 min) of stimulation, the left kidney was also removed and IRR content assessed. Renal blood flow and renin secretory rate (RSR) were determined frequently at baseline and following stimulation of renin secretion. The total amount of renin secreted in response to acute stimulation was calculated by integrating the RSR response over time. RSR from the left kidney increased by 515% during acute stimulation. IRR content in the left kidney also increased and averaged 16% greater than the right kidney from the same animal. In order to account for all of the renin secreted as well as the increase in IRR content following acute stimulation, it was calculated that the renin synthesis rate would have been required to increase over 26-fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232487 TI - Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease. AB - Normotensive rats of the Milan strain (MNS) spontaneously develop focal glomerulosclerosis. In order to explore the contribution of glomerular thromboxane (TX) A2 synthesis to the development of the disease, we have characterized the time course of renal functional and biochemical changes, and their modification by long-term treatment with a TX-synthase inhibitor. Oral administration (150 mg.kg-1 from 1 to 14 months of age) of FCE 22178 suppressed enhanced glomerular TXB2 production at all experimental times (mean inhibition 80%) and proteinuria (varying between 27.1 and 73.0%) while preserving renal blood flow and glomerular filtration rate. These effects of TX-synthase inhibition were seen in the absence of any statistically significant changes in systemic blood pressure. Moreover, FCE 22178 had no antihypertensive effects in hypertensive rats of the Milan strain (MHS) nor in spontaneously hypertensive rats (SHR). Treatment also prevented the age-related hypoalbuminemia and hyperlipidemia observed in control MNS and significantly (P less than 0.01) reduced glomerular histologic damage, as demonstrated by light microscopy studies and measurement of sclerotic area. We conclude that: 1) MNS rats provide an animal model of long-lasting proteinuria characterized by an age-related increase in glomerular TXB2 production paralleled by progressive loss of renal structural integrity and function and by a secondary dyslipidemia; 2) pharmacological inhibition of glomerular TX-synthase attenuates the structural as well as the functional expression of kidney disease, without a primary effect on systemic blood pressure. These data are suggestive of an important modulating role of TXA2 in the progression of MNS renal disease. PMID- 2232488 TI - Mild ischemia predisposes the S3 segment to gentamicin toxicity. AB - The purpose of these studies was to determine if a functionally insignificant ischemic insult, occurring prior to gentamicin administration, enhanced gentamicin nephrotoxicity. Bilateral renal pedicle clamp studies demonstrated that 15 minutes of ischemia did not increase the plasma creatinine yet markedly enhanced gentamicin nephrotoxicity. Further studies, in uninephrectomized rats, demonstrated that following fifteen minutes of renal ischemia and four hours of reperfusion inulin clearance, FENa+ and cellular morphology were normal. This model, therefore, was used in all subsequent studies. While the plasma creatinine concentrations were normal 24 hours following 15 minutes of ischemia and only slightly increased following gentamicin administration (100 mg/kg, i.p.) gentamicin administered four hours following 15 minutes of renal ischemia resulted in significantly increased 24-hour plasma creatinine values. Light microscopic quantitation of tissue injury, performed 24 hours following experimental manipulation, was notable for S3 segment damage in the ischemia plus gentamicin group. This was not observed in either the ischemia group or the sham operated gentamicin group. Cortical gentamicin levels were elevated in the ischemia plus gentamicin group, despite similar plasma gentamicin half-lives. However, the elevation in cortical gentamicin levels was dissociated from the enhanced nephrotoxicity seen following mild ischemic injury. Taken together these data indicate that mild renal ischemia, occurring prior to gentamicin administration, greatly enhanced gentamicin nephrotoxicity with the greatest damage occurring to S3 cells. PMID- 2232489 TI - A phenomenological interpretation of the variation in dialysate volume with dwell time in CAPD. AB - Intraperitoneal fluid volume (IPV) changes versus time were followed in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using a simple volume recovery method. In each patient dialysates containing 1.36 and 3.86 percent glucose as an osmotic agent were investigated. The patients' IPV versus time data were fitted to a function determined by four "arbitrary" coefficients, from which both the initial ultrafiltration (UF) rate immediately following intraperitoneal (i.p.) fluid instillation and the "final" peritoneal-to-blood fluid absorption rate could be assessed. The peritoneal osmotic conductance to glucose, that is, the peritoneal ultrafiltration coefficient (Kf), times the peritoneal osmotic reflection coefficient to glucose (sigma g), Kf sigma g, was determined using two related approaches. Kf sigma g is a major determinant of the transperitoneal volume exchange, and it was calculated to be 3.54 +/- 0.85 (+/- SE) and 3.81 +/- 0.52 microliters/min/mm Hg, respectively, depending on the assumption employed. Kf sigma g was further analysed according to a three-pore model of membrane permeability to determine the possible range of Kf and sigma g compatible with a peritoneal small solute sieving coefficient (phi) ranging from 0.3 to 0.61. According to these calculations both Kf and sigma g ranged from 0.043 to 0.081 (ml/min/mm Hg and dimensionless, respectively). The maximal peritoneal lymph flow (L) realistic according to this analysis, and compatible with a measured total peritoneal-to-blood fluid absorption rate of 1.25 +/- 0.14 ml/min, was 0.75 ml/min, the most plausible values, however, falling between 0.3 to 0.5 ml/min. PMID- 2232490 TI - Proximal nephron and renal effects of DuP 753, a nonpeptide angiotensin II receptor antagonist. AB - The purpose of these studies was to quantitatively assess the role of endogenous angiotensin II activity in controlling transport in the proximal convoluted tubule (PCT) and whole nephron. We used the nonpeptide angiotensin II receptor antagonist DuP 753, which lacks the agonist and kinin/prostaglandin-inducing properties of saralasin and captopril, respectively. During in vivo microperfusion in the Munich-Wistar rat, we found that DuP 753 had a powerful inhibitory effect on bicarbonate (370 +/- 3 to 200 +/- 9 pEq/mm.min, P less than 0.001), chloride (214 +/- 3 to 105 +/- 9 pEq/mm.min, P less than 0.001), and water (5.2 +/- 0.1 to 2.8 +/- 0.2 nl/mm.min, P less than 0.001) absorption in the S1 subsegment of the PCT. At maximally effective doses, DuP 753 (10 mg/kg i.v.) was significantly more effective than was captopril (3 mg/kg i.v.) in inhibiting sodium chloride transport in the S1 PCT. DuP 753 is the most potent diuretic ever described in this segment. Consistent with the axial decline of angiotensin II receptor density in the PCT, DuP 753 was a less effective transport inhibitor in the S2 subsegment of the PCT, similar to captopril. Though downstream reabsorptive elements partially compensate for the action in the earliest segment of the nephron, we also showed using free-flow micropuncture and clearance techniques that DuP 753 induces a substantial diuresis, natriuresis and chloruresis. In conclusion, the marked decrease in S1 PCT fluid and electrolyte absorption induced by DuP 753 indicates that endogenous angiotensin II exerts significant tonic support of proximal transport in vivo. PMID- 2232491 TI - Improvement of brain function in hemodialysis patients treated with erythropoietin. AB - To evaluate the effects of recombinant human erythropoietin (rHuEPO) on brain function, 15 chronic hemodialysis patients were studied by event-related P300, stimulus-related evoked potentials, and trailmaking before (hematocrit 22.7%) and after rHuEPO (hematocrit 30.6%). P300 peak latency elicited by a tone discrimination paradigm improved (391 before vs. 366 ms after; Cz = vertex; P less than 0.01) confirming beneficial effects on cerebral cognitive processing. P300 amplitude (13.6 vs. 15.8 microV; P = 0.06) and trailmaking tended to improve (55 vs. 43 s). P300 measures were influenced by low hemoglobin levels before rHuEPO (P less than 0.01), suggesting that severe anemia may contribute to uremic brain dysfunction. Furthermore, decrease of stimulus-related auditory brainstem I V interpeak latency (4.28 before vs. 4.17 ms after; P less than 0.05) and increase of somatosensory N20/P25 amplitude (4.8 vs. 7.0 microV; P less than 0.05) pointed to improvement of sensory pathways by mechanisms unrelated to cognition. Brain dysfunction in chronic hemodialysis patients may, beside other factors, in part be caused by severe anemia and can be improved by rHuEPO treatment. PMID- 2232492 TI - Effect of in vivo contact between blood and dialysis membranes on protein catabolism in humans. AB - To investigate whether the contact between blood and dialysis membranes might induce muscle protein degradation, the exchange of free amino acids across leg tissues was measured by catheterization technique in three groups of healthy subjects before and after a 150 minute sham-hemodialysis procedure (SHDP), that is, in vivo passage of blood (100 ml/min) through a dialyzer but with no circulating dialysate. Dialyzers with either regenerated cellulose membrane (group CU, N = 10 and group CU-IND, N = 6) or polyacrylonitrile membrane (group AN, N = 8) were used in group CU-IND indomethacin was administered before (100 mg) and at the end (50 mg) of SHDP. Leg blood flow was measured by venous occlusion plethysmography. In group CU net leg release of tyrosine and phenylalanine increased from 3.4 +/- 0.8 and 3.6 +/- 0.8 nmol/min/100 g tissue, respectively, before SHDP to 7.8 +/- 1.8 and 8.3 +/- 1.8 nmol/min/100 g tissue, respectively, at 345 minutes after the start of SHDP (P less than 0.01). The total release of all measured amino acids increased from 148 +/- 31 to 309 +/- 50 nmol/min/100 g tissue (P less than 0.01). The results indicate that interaction between blood and regenerated cellulose membranes leads to accelerated net protein breakdown. In group CU-IND no change in leg amino acid release was observed following SHDP, suggesting that the increased net protein catabolism is mediated by prostaglandins. Sham hemodialysis using AN membranes did not result in increased amino acid efflux from leg tissues, implying that the protein catabolic effect of blood-membrane contact depends on the biochemical properties of dialyser. PMID- 2232493 TI - Peritoneal transport in CAPD patients with permanent loss of ultrafiltration capacity. AB - During a 10 year period, 14 out of 227 patients (6.2%) undergoing continuous ambulatory peritoneal dialysis (CAPD) developed permanent loss of ultrafiltration capacity (UFC). The risk of UFC loss increased from 2.6% after one year to 30.9% after six years of treatment. A six hour, single dwell study with glucose 3.86% dialysis fluid was carried out in nine of the UFC loss patients and in 18 CAPD patients with normal UFC. Intraperitoneal dialysate volumes were calculated using 131I-tagged albumin (RISA) as volume marker with a correction applied for its elimination from the peritoneal cavity. The RISA elimination coefficient (KE), which can serve as an estimation of the upper limit of the lymphatic flow, was also calculated. Diffusive mass transport coefficients (KBD) for investigated solutes (glucose, creatinine, urea, potassium, total protein, albumin and beta 2 microglobulin) were calculated during a period of dialysate isovolemia. Two patterns of UFC loss were observed: (a) seven patients had high KBD values for small solutes resulting in rapid uptake of glucose, whereas KBD values for proteins were normal; (b) two patients had normal KBD values but a threefold increase both in the fluid reabsorption rate and KE. We conclude that loss of the osmotic driving force (due to increased diffusive mass transport for small solutes) and increased fluid reabsorption (possibly due to increased lymphatic reabsorption) are the two major causes of permanent loss of UFC in CAPD patients. PMID- 2232494 TI - Removal of an inorganic acid load in subjects with ketoacidosis of chronic fasting. AB - When a large inorganic acid load is ingested by normals, the proton load is eliminated because the rate of excretion of ammonium can rise to 200 to 300 mmol/day. In subjects with ketoacidosis of chronic fasting, such a large increase in the rate of excretion of ammonium might not be possible because of ATP balance considerations in proximal cells. Subjects with ketoacidosis of chronic fasting excreted less net acid as defined in the conventional way when they consumed a large inorganic acid load (136 +/- 6 vs. 176 +/- 26 mmol/day in control fasted subjects). Nevertheless, the vast majority of this inorganic acid load was eliminated because they were in steady state and had only a slightly lower concentration of bicarbonate (13 +/- 0.6 vs. 15 +/- 0.5 mmol/liter) and ketoacid anions (3.3 +/- 0.2 vs. 5.5 +/- 0.2 mmol/liter) in their blood. Using a definition of net acid excretion where the component of bicarbonate loss was expanded to include "potential bicarbonate" (ketoacid anions) in the urine, the rate of excretion of net acid was higher in subjects who ingested the inorganic acid load, owing to a much lower rate of excretion of ketoacid anions (9 +/- 2 vs. 120 +/- 7 mmol/day). This lower rate of excretion was not only due to a lower filtered load, but also to a higher fractional reabsorption of ketoacid anions during acidosis (97 +/- 0.1 vs. 77 +/- 0.2%). This higher fractional reabsorption could not be explained by a lower filtered load of ketoacid anions or to a restricted intake of sodium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232495 TI - Angiotensin II receptor regulation in anti-glomerular basement membrane nephritis. AB - The expression of the glomerular receptor for angiotensin II (Ang II-R) was examined longitudinally following the induction of anti-glomerular basement membrane (GBM) nephritis in the rat. The specific aim of the project was to determine whether immunologically-induced glomerular injury led to significant abnormalities of the relationship between glomerular Ang II-R and its circulating ligand, Ang II. Scatchard analysis was used to measure Ang II-R on purified glomeruli at selected time intervals over two months following a single dose of sheep anti-rat GBM antibody. Corresponding values for plasma Ang II were determined. Receptor density fell to approximately 50% by 16 hours following the injection of antibody (control 96.4 +/- 9.3 x 10(6); nephritic 52.6 +/- 5.6 x 10(6) receptors/glomerulus; P less than 0.001) and there was a corresponding threefold increase in plasma Ang II (control 21.0 +/- 2.5; nephritic 66.6 +/- 20.6 pg/ml; P less than 0.01). However, this reduction in receptor binding could not be explained by the rise in plasma Ang II concentration, as effective blockade of the RAS by enalapril did not alter receptor expression (56.1 +/- 4.6 x 10(6) receptors/glomerulus). Subsequently, a rise in receptor density and a corresponding fall in plasma Ang II were observed: three days after antibody administration, receptor concentration had increased significantly above control values (150.5 +/- 11.9 x 10(6] while plasma Ang II was undetectable (that is, less than 5 pg/ml). Ang II-R remained elevated for the next two weeks but returned to normal four to eight weeks after the administration of nephrotoxic antibody.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232496 TI - Renal biopsy. PMID- 2232497 TI - Australasian Society of Nephrology 26th annual meeting. Brisbane, Queensland, Australia, March 14-16, 1990. Abstracts. PMID- 2232498 TI - Renal regulation of extracellular fluid composition. Symposium in honor of Donald W. Seldin, M.D. PMID- 2232499 TI - Physiologic adaptations of the tubuloglomerular feedback system. AB - Knowledge of the existence of a tubuloglomerular feedback system has been available for many years. Only recently, however, have tenable hypotheses and supporting experimental data become available which have served to provide details regarding the complex inner workings of this system. The facility for examining this integrated physiologic network has derived, in large part, from the routine ability to perform in vivo micropuncture. We anticipate that further advances in this field will hinge on the development of additional experimental techniques to allow cellular biologic aspects of the system to be closely monitored in situ. PMID- 2232500 TI - Influence of converting enzyme inhibition on glomerular filtration rate and proteinuria. PMID- 2232501 TI - Role of branched-chain ketoacids in protein metabolism. PMID- 2232502 TI - Cellular mechanisms of prostaglandin E2 and vasopressin interactions in the collecting duct. PMID- 2232503 TI - Defenses of an unstable compromise: crystallization inhibitors and the kidney's role in mineral regulation. PMID- 2232504 TI - Determinants of renal damage in rats with systemic hypertension and partial renal ablation. PMID- 2232505 TI - Inhibition of 11 beta-hydroxysteroid dehydrogenase and its effect on epithelial sodium transport. PMID- 2232506 TI - Countercurrent system. AB - Urinary concentration is achieved by countercurrent multiplication in the inner medulla. The single effect in the outer medulla is active NaCl absorption from the thick ascending limb. While the single effect in the inner medulla is not definitively established, the majority of experimental data favors passive NaCl absorption from the thin ascending limb. Continued experimental studies in inner medullary nephron segments will be needed to elucidate fully the process of urinary concentration. PMID- 2232508 TI - Catastrophic medical events with exhaustive exercise: "white collar rhabdomyolysis". PMID- 2232507 TI - Renal control of extracellular calcium. PMID- 2232509 TI - Disorders of distal acidification. PMID- 2232511 TI - Chronic tubulo-interstitial nephritis: correlation between structural and functional findings. PMID- 2232510 TI - Renal handling of citrate. PMID- 2232512 TI - Single-nephron studies: implications for acid-base regulation. PMID- 2232513 TI - [Some new treatment strategies for lung involvement in patients with mucoviscidosis]. AB - Autogenic drainage, PEP mask breathing as well as physical exercise are now well established in the treatment of pulmonary disease in cystic fibrosis, but there are different opinions about oxygen therapy over a long period as well as corticosteroid treatment. First reports on amiloride inhalations seem to be hopeful, but there is no experience with cystic fibrosis children till now, therefore clinical use can not be recommended. Heart lung transplants are not to consider as an alternative treatment for all cystic fibrosis patients, in special cases it may be successful. PMID- 2232514 TI - [Problems of perinatal transmission of hepatitis B]. AB - This review of recent publications and of the results of our own research brings our insights into the perinatal transmission of hepatitis B up to date. It includes facts concerning epidemiology, means of transmission, serological detection and problems of infection specific to newborns. The detailed discussion of the issue of prevention is intended to serve the basic objective of counteracting the further spread of the hepatitis B virus by a systematic screening of all pregnants followed by immunoprophylaxis for the newborns. PMID- 2232515 TI - [Micturition retention and urinary tract infection in girls. Detection of functional micturition disorders with special reference to anamnesis]. AB - The normalization of functional micturition disturbances obtains an increasing importance in the treatment and guidance of girls with urinary tract infections. Our experience in the detection of an abnormal micturition pattern is reported. A detailed interrogation of the parents feasible in any outpatient practice is more emphasized than investigations by means of technical devices. PMID- 2232516 TI - [Frontonasal dysplasia. Case report and review of the literature]. AB - FND is a non-uniform malformation complex with symptoms ranging between severe hypertelorism with bidfid nose and cranium bidfidum occultum with agenesis of the corpus callosum. Etiology and pathogenesis are discussed on the basis of a case history and some hints regarding differential diagnosis and genetic counselling are given. The exclusively sporadic occurrence of FND tells against a hereditary pathomechanism. Consequently, there is no recurrence risk. However, in families with an affected child, malformations generally tend to occur a little more often. PMID- 2232517 TI - [The value of sleep EEG following sleep deprivation before terminating anticonvulsive therapy in epileptic children and adolescents]. AB - A sleep electroencephalogram was carried out after deprivation of sleep in 70 epileptic children and young people. The EEG was done before an intended reduction of anticonvulsants. Patients who had generalized paroxysmal patterns in the sleep EEG suffered from significantly more frequent relapse after and of therapy than those ones with local paroxysmal activity or electroencephalogram without paroxysmal activity respectively. A sleep EEG after deprivation of sleep should be carried out before a decision is made on the end of the therapy in patients with expected generalized paroxysmal patterns. PMID- 2232518 TI - [The microbial colonization pattern of newborn infants. What is its significance? Results of a study at a district hospital in the Gera district]. AB - A microbiological investigation was performed under standardized conditions both on mother and child for total of 151 births, 112 of which being classified as normal, the remainder of 39 as risk births. Significant differences were found between the microbial colonization patterns for normal and risk births, respectively, as judged from cultures of smears from maternal cervices and from their neonates. In addition, colonization patterns of the newborn children turned out to be age-dependent. No correlation between the colonization pattern of the neonatal surface and infections of the newborn infants has been found. PMID- 2232519 TI - [Post-hypoglycemic encephalopathy in type I diabetes mellitus in childhood and its treatment]. AB - In type-I-diabetes insuline-induced hypoglycaemia is the most frequent and permanent therapeutic complication. In severe courses proceeding to unconciousness, it is essential to decide on the irritation of exclusively cortical or subcortical structures. The latter one is classified as posthypoglycaemic encephalopathy correlated with a relatively high lethality. Consequently, differential diagnosis and carefully calculated treatment are of vital importance. PMID- 2232520 TI - [Surgical treatment of diseases of the brachiocephalic arteries]. AB - The authors have summarized the experience with surgical treatment of 147 patients with the brachiocephalic arterial pathology. Transient disorders in the cerebral circulation were noted in 54%, chronic vascular cerebral insufficiency- in 15%, ischemic insult and its sequelae--in 19% of the patients. Occlusive stenotic lesions of the extracranial vessels, aneurysms, tortuosity of the brachiocephalic++ trunk, compression of the carotid arteries by chemodectoma were the indications for operative treatment. When choosing a method for operative intervention, the preference was given to extrathoracic techniques. The positive results were achieved in 90% of the patients. PMID- 2232521 TI - [Use of ultrasonics and antibiotics in the treatment of wounds in patients with high risk of infection of vascular transplants]. AB - The level of bacterial colonization of the operative wounds in performance of the reconstructive operations on the vessels equal to 10(3) bacteria in 1 g of tissue is critical for the development of suppuration. The use for treating the wounds of the low-frequency ultrasound and gentamycin solution in 17 patients permitted to reduce the critical level of bacterial wound colonization, and due to this, to decrease the incidence of the purulent-septic complications from 35.7 to 5.9%. In 14 patients after the operations for late reocclusion performed in presence of cicatrices of the tissues, there was no wound suppuration. PMID- 2232522 TI - [Roentgenoendovascular dilatation of the renal arteries in the treatment of vasorenal hypertension]. AB - The possibilities of the use of roentgenoendovascular dilatation of the renal artery were studied in 57 patients with stenosis of the renal artery and vasorenal hypertension. The authors managed to perform the manipulation in 48 patients. Occlusion of the renal artery, pronounced atherosclerosis of the iliac and axillary arteries, coarctation of the aorta were the causes of failure. In 52.6% of the patients, the "residue" of stenosis was less than 30% of the normal arterial lumen, in 31.6%--30-50%, in the remaining patients, the dilatation has failed. Stable normotension was achieved in 39.5%, the state improved in 50% of the patients. The absence of hypotensive effect for the first 6 mos after the operation was caused by recurrency of the dilated artery stenosis, which resulted from the improper choice of a balloon catheter. The diameter of such a catheter should be 100-110% of a width of the renal arterial lumen proximally to stenosis. The later recurrency of hypertension was caused by the development of the stenosis of the artery of the contralateral kidney. PMID- 2232523 TI - [Tissue oxygen metabolism, hemodynamics and microcirculation in vasorenal hypertension in patients with different types of blood circulation]. AB - The authors examined 68 patients with vasorenal hypertension (VRH). In hyperkinetic type of VRH, the tissue hypoxia is caused by the increase in the cardiac index and rate of blood flow, changes in the microcirculation; in hypokinetic type--by decrease in the cardiac index, sharp increase in the specific peripheral vascular resistance and pronounced changes in all the links of microcirculatory channel as well is observed. Timely correction of the hyperkinetic type of VRH in patients leads to normalization of hemodynamics and elimination of tissue hypoxia. After correction of the hypokinetic type of VRH in patients, neither hemodynamics, nor impairment in the oxygen regimen of the tissues normalizes, even if the positive effect of treatment is noted. PMID- 2232524 TI - [Changes in peripheral hemodynamics in patients with chronic circulatory insufficiency in the extremities after the treatment by reinfusion of UV irradiated blood]. AB - Reinfusion of the blood irradiated with the ultra-violet rays in patients with chronic insufficiency of the blood supply of the extremities leads to significant increase in the linear and volumetric blood flow rate in the damaged extremities, improvement in the microcirculation, reduction in the blood viscosity. The effect doesn't depend on the genesis of occlusion and degree of the impairement of circulation. PMID- 2232525 TI - [Venous hemodynamics in chronic occlusive diseases of arteries of the lower extremities]. AB - The authors have revealed a gradual development of venous hypertension and deceleration of the rate of venous blood flow in the damaged extremities in chronic obliterative arterial diseases. Decompensation of arterial hemodynamics is accompanied by the development of pronounced venous congestion with reduced venous pressure and tension. This may cause the incompetence of the deep venous valves. PMID- 2232526 TI - [Possibilities of prevention of pulmonary thromboembolism in patients with vascular pathology according to clinical data and patho-anatomical studies]. AB - In a work, the retrospective analysis of the case records and materials of the postmortem studies in 42 patients with pathology of the major vessels, who died from pulmonary thromboembolism, is presented. A number of pathogenetic mechanisms of the development and ways for prophylaxis of this complication is considered. PMID- 2232527 TI - [Various aspects of prognosis, treatment and prevention of pulmonary thromboembolism]. AB - In a work, the analysis of sectional investigations in 47 patients, who died from pulmonary thromboembolism (PTE), is presented. The causes and results of treatment of PTE after operation in 34 patients are studied. The non-specific and specific measures for PTE prophylaxis are suggested. PMID- 2232529 TI - [Pre-amputation freezing of the extremity in acute ischemic gangrene]. AB - When preparing for amputation in 153 patients with acute ischemic gangrene of a lower extremity, the tourniquet-cold isolation was used. In 137 patients, the damaged extremity was freezed by means of a special portable freezing chamber, which can be used in any surgical in-patient department. The duration of cooling ranged from 18 hrs to 14 days. The state improved in 136 patients, the amputation of the extremity was performed in them. The use of freezing of the damaged extremity permitted to reduce the postoperative lethality from 41 to 19.1%. A high effectiveness of the method in gangrene of the extremity against the background of diabetes mellitus was noted. PMID- 2232528 TI - [Current methods of the treatment of varicocele]. AB - The results of complex examination and treatment of 172 patients with varicocele are presented. Roentgenoendovascular occlusion of the testicular vein was performed in 52 patients with the positive result in 43 of them. The disease recurrence was revealed in control examination 6 mos later in 9 patients. A new microsurgical operation of creating the double spermatico-venous++ anastomosis, which permits to accomplish the more complete correction of venous hemodynamics in the system of the testicular vein, to reduce the traumatism of the operation, to improve the conditions for normalization of spermatogenesis, is suggested. A recurrence of varicocele after its treatment by means of the microsurgical correction occurred in 1 patient. Of the 56 women, whose husbands suffered from infertility, after microsurgical operations performed for varicocele, the pregnancy resulted in 19. PMID- 2232530 TI - [Quantitative evaluation of hemodynamics in varicose veins]. AB - The experience with the clinical use for many years of the quantitative plethysmographic indices for solving the diagnostical and tactical problems in varicose disease has shown their advantage over the clinical and roentgenophlebographical signs in detecting the presence and degree of retrograde blood flow in the perforating veins of a crus, making clear distinction between the stages of compensation and decompensation with subdivision of the latter into the subgroups according to the pronouncement of perforans shunting, choice of a method for operation. PMID- 2232531 TI - [Status of the musculo-venous pump of the thigh in varicose veins]. AB - By means of the ultrasound flowmetry, phlebography, rheovasography and phlebotonometry, 51 patients with varicose disease was examined. It was established, that musculo-venous++ "pump" of a thigh played the leading part in the venous return. In stages I and II of varicose disease, the function of musculo-venous++ "pump" of a thigh was impaired moderately, its sharp disfunction was noted in stage III of the disease. PMID- 2232532 TI - [Comparative characteristics of the forearm and crus as donor sites for obtaining composite skin flaps on vascular pedicles]. AB - The ++topographo-anatomical investigations on 67 forearms and 58 crura permitted to establish the possibility for formation of the free similar types of island composite cutaneous flaps on the large vascular bundles. On the crus, the possibility to elevate two more types of the island cutaneous flaps without transection of the major vessels is substantiated. The variants of microsurgical autotransplantation and trasplantation+ of the composite cutaneous flaps of the forearm and crus on the vascular pedicles are discussed. PMID- 2232533 TI - [The "steal" syndrome in patients with occlusive diseases of the aorta and iliac arteries]. AB - In the work, the findings of clinical, functional and angiographic investigations in patients with the "steal" syndrome are systematized. In 39 of the 152 patients with atherosclerosis of the vessels of the aortoiliofemoral segment, the two forms of the "steal" syndrome (external iliac and pelvic "steal") causing the arterial erectile impotence were revealed. For objectivization of the syndrome, a test of "coitus loading" on the muscles of the lower extremities was used. PMID- 2232534 TI - [Possibilities of improving the methods of making vascular prostheses using human umbilical veins]. AB - In the experiment, the possibilities for intensification and acceleration of the umbilical vein tissue stabilization, increasing the strength and improving the plastic properties, increasing the resistance of biological grafts to thrombosis due to the use of the improved method of conservation according to the scheme: dynamic stabilization in the glutaraldehyde-enzyme-glutaraldehyde-heparin solution are studied. The developed biological grafts were used in 12 patients with occlusion of the arteries of the femoropopliteal segment. After 18 mos, the grafts are patent in 8 patients. PMID- 2232535 TI - [Ultrastructure of skin flaps obtained in vivo by graded tissue expansion of different intensity]. PMID- 2232536 TI - [Surgical treatment of circulatory disorders in the upper extremities]. AB - The authors operated on for circulatory disturbances in the upper extremities 216 patients. Differential approach to the choice of a method for surgical correction permitted to achieve excellent and good results in 89% of them. PMID- 2232537 TI - [Surgical tactics in aneurysm of the abdominal aorta]. AB - The results of treatment of 164 patients with aneurysms of the abdominal aorta are summarized. Of these patients, 95 were operated on. Realization of the developed tactics of treatment permitted to reduce the incidence of postoperative complications 3.8-fold, and lethality--5.3-fold. PMID- 2232538 TI - [Thrombembolectomy in the treatment of patients with acute disorders of mesenteric circulation]. AB - In acute impairement of the mesenterial circulation, the authors in 31 patient performed thrombembolectomy from the superior mesenteric artery, which in 22 was supplemented with resection of a necrotized area of the intestine. Five patients recovered. In these patients within the first 24 hours, the control relaparotomy was performed and the early postischemic disorders were cupped off with the use of tubal decompression, active aspiration of the intestinal contents, lavage of the intestine with the balanced electrolyte solution, hemosorption and intraintestinal administration of the oxygenated 10% glucose solution. PMID- 2232539 TI - [Direct long-term endolymphatic treatment of patients with arterial occlusive diseases of the lower extremities]. PMID- 2232540 TI - [Non-invasive diagnosis of the degree of aortic coarctation]. AB - Examined were 42 patients with aortal coarctation at the age of from 6 to 35 years. The differences in hemodynamics, microcirculation and oxygen regimen of tissues depending on the degree of aortal coarctation were revealed. To diagnose the degree of aortostenosis, it is suggested to use the transcutaneous monitoring of PO2 distally to the site of coarctation. PMID- 2232541 TI - [Ultrasonic vascular scanning in the diagnosis of acute arterial obstruction]. AB - In thrombosis of the aorta and major arteries (52 cases), postthrombotic occlusion (26), arterial embolism (14), the ultrasound vascular scanning++ was performed. The method permits to define the presence and location of arterial occlusion, differentiate thrombosis and embolism, atherosclerotic and autoimmune diseases of the vessels and as well to assess the outcome of restorative and reconstructive operations in acute arterial obstruction. PMID- 2232542 TI - [Possibilities of Doppler ultrasonics in the diagnosis of lesions of the brachiocephalic arteries]. PMID- 2232543 TI - [Use of Doppler ultrasonics in the diagnosis of postphlebitic syndrome]. PMID- 2232544 TI - [Surgical correction of valvular insufficiency of deep varicose veins of the lower extremities]. AB - A scheme for preoperative examination of the patients with varicose disease is presented. Incompetence of the deep venous valves was revealed in 74.1% of the patients with varicose disease and in 76.5%--with its postoperative recurrences. Correction of ++phlebo-hemodynamics was accomplished by means of a carcass spiral, fascial paravasal structures and suggested by the authors method of placing the three corrective ligatures, which has proved to be the most effective. One hundred and forty two operations on the deep veins were performed in 102 patients. In observation for up to 4 years, in 94.7% the excellent and good results were noted. PMID- 2232545 TI - [Autologous venous prosthesis in microsurgery]. PMID- 2232546 TI - [Use of external brachial cutaneo-fascial flap for plastic microsurgery of defects of functionally important areas of the hand and foot]. AB - On the basis of morphological investigations on 20 non-fixed cadavers, the microsurgical anatomy of the external fasciocutaneous brachial flap was detailed . A flap was successfully used for plasty of the tissue defects of the foot, forearm and hand in 14 patients. The recommendations concerning the technique of flap elevation and transplantation are given. PMID- 2232547 TI - [Effect of lumbar sympathectomy on late results of reconstructive operations on the abdominal aorta and arteries of the lower extremities]. AB - The use of reconstructive operation in combination with lumbar sympathectomy for the treatment of obliterative lesion of the vessels of the aortoiliofemoral segment permits to reduce the incidence of development of the early postoperative vascular thrombosis and late reocclusion. A good patency of vascular transplants after combined operation was noted in 62% of cases, after isolated reconstruction -in 38%. PMID- 2232548 TI - [Lumbar sympathectomy in patients with arteriosclerosis obliterans of the lower extremities and diabetes mellitus]. AB - In 72 patients with obliterative atherosclerosis of the arteries of the lower extremities and diabetes mellitus, the lumbar sympathectomy was performed. A good result was noted in 35 of them, amputation of the extremity was performed in 8 patients. Lumbar sympathectomy is indicated to the patients in initial stages of the disease. PMID- 2232549 TI - [Optimal hemodynamic conditions for performing reconstructive- restorative operations on the aorto-femoral segments]. AB - According to the results of examination of 170 patients with atherosclerotic lesions of the vessels of the aortofemoral segment and 170 virtually healthy subjects by means of the tetrapolar rheography, the prognostic value of the hypokinetic type of circulation in the development of cardiologic complications after reconstructive operations on the vessels mentioned was established. It is admitted that the value of cardiac index equal to 1.4 l/(min.m2) is a contraindication for the performance of reconstructive-restorative operations on the vessels of the aortofemoral segment. PMID- 2232550 TI - [Treatment of complicated retroampullar duodenal ulcers]. AB - Of the 450 patients with complicated duodenal ulcer disease, in 23 (5.8%) the ulcer was located distally to the duodenal ampulla. On the basis of studying the results of surgical treatment, a conclusion is made, that the selective proximal vagotomy in combination with the ulcer excision and duodenoplasty is an operation of choice in complicated retroampullary ulcers. The operative interventions correcting the disturbances in the duodenal patency in preserved function of the pyloric sphincter contribute to prevention of duodenogastric reflux and alkaline reflux-gastritis. PMID- 2232551 TI - [Varicose dilatation of the external pudendal vein in a pregnant woman, simulating inguinal hernia]. PMID- 2232552 TI - [Complications of central venous catheterization]. PMID- 2232553 TI - [Complications of surgical treatment of patients with non-organic neoplasms of the small pelvis]. PMID- 2232554 TI - [Tactics in the surgical treatment of aortic thrombosis in suppurative-necrotic lesions of the lower extremities]. PMID- 2232555 TI - [Rupture of aneurysm of the abdominal aorta to the inferior vena cava]. PMID- 2232556 TI - [Thrombosis of mesenteric blood vessels in a patient after intestinal surgery]. PMID- 2232557 TI - [Endolymphatic therapy in vascular surgery]. PMID- 2232559 TI - [Diagnosis of the acute phase of peripheral nonspecific aortoarteritis]. PMID- 2232558 TI - [Successful treatment of thromboembolism of the artery of the solitary kidney]. PMID- 2232560 TI - [Recurrent and residual echinococcosis of the abdominal organs]. AB - The article gives information on 14 patients who were operated on for a second time for echinococcosis of various localization. The authors conclude that all cases in which the carrier of the germ elements of the parasite remains in the organism should be logically called residual and not false recurrence. A disease caused by a new infection should be called ++re-invasive echinococcosis but not a true recurrence. PMID- 2232562 TI - [Internal fistulas of bile ducts caused by cholelithiasis]. AB - Operative treatment of 41 patients is analysed. It is shown that internal fistulas of the bile tract are severe complications of cholelithiasis. Late detection and treatment of diseases of the biliary system is the main cause of formation of the fistulas. Removal of the internal biliary fistula as well as correction of abnormal changes in the bile ducts is the object of the operative intervention. The postoperative fatality was 12.2%. PMID- 2232561 TI - [Precision sutures of bile ducts in experimental cholangitis]. AB - Experimental study of the use of the precision suture techniques in application to the hepaticocholedochus and in formation of biliodigestive anastomoses in cholangitis revealed the advantages of the precision suture over the "traditional" one. The precision suture is very strong and air-tight, provides adequate adaptation of the coats of the hepaticocholedochus and the small intestine and creates thus optimum conditions for healing; when used in combination with absorbable suture material it excludes the formation of ligature cholelithiasis and reduces the risk of cicatricial stenosis. PMID- 2232563 TI - [Combined interventions in non-organic neoplasms of the small pelvis]. AB - Experience with 62 combined operations on patients with nonorganic new growths of the true pelvis is discussed. They accounted for 33.3% of 227 radical interventions undertaken for this disease. The ages of the patients ranged from 4 months to 64 years. Ten patients were admitted after exploratory laparotomies. Benign new growths were diagnosed in 14 and malignant new growths in 48 patients. Different variants of operative approaches were used. Most frequently the tumor was resected together with bones, iliac vessels, genitalia, and urinary bladder. Various complications were noted in 39 patients who were operated on. Hemorrhage was the most frequent and menacing complication--in 26 patients. Two patients died. Recurrences were found in 8 of a group of 60 patients discharge from the clinic. After combined operations for malignant nonorganic tumors of the true pelvis 3-year survival was 36.0%, 5-year survival was 29.4%. PMID- 2232564 TI - [Causes of respiratory insufficiency in acute pancreatitis]. PMID- 2232565 TI - [Inflammatory processes in soft tissues and osteomyelitis caused by bone nails]. PMID- 2232566 TI - [A method of determining intestinal viability]. PMID- 2232567 TI - [Intestinal intubation in peritonitis]. PMID- 2232568 TI - [Late results of selective proximal vagotomy with transverse gastroduodenal anastomosis in pyloric stenosis caused by duodenal ulcer]. AB - The late-term results of treatment of pyloroduodenal ulcerous stenosis by means of selective proximal vagotomy (SPV) in combination with transverse gastroduodenoanastomosis (GDA) were studied in 110 patients. The results are compared with those of SPV combined with longitudinal GDA after Jaboulay. Clinical, radiological, endoscopic, biochemical, and morphological examination showed the advantages of transverse GDA over longitudinal GDA. It is concluded that combination of SPV with transverse GDA is the operation of choice. PMID- 2232569 TI - [Duodenal obstruction caused by cholelithiasis]. PMID- 2232570 TI - [Rare cause of relaparotomy]. PMID- 2232571 TI - [Internal incarceration of the small intestine]. PMID- 2232572 TI - [Fulminant gangrene of the scrotum]. PMID- 2232573 TI - [Fournier's disease in a patient after relaparotomy in postoperative peritonitis]. PMID- 2232574 TI - [Cancer of the gallbladder]. PMID- 2232575 TI - [Multiple organ failure syndrome in surgery]. PMID- 2232576 TI - [Repeated operations in gastric and duodenal ulcers]. AB - The results of repeated operations in 165 patients were studied. A second operative intervention was indicated most frequently after closure of a perforating ulcer (h = 126). The character of the second operative intervention was determined by the method of the previous operation and the complication of the ulcer for which the operation had to be repeated, the patient's condition and age, and the urgency of the surgery. The mortality rate after repeated operative interventions was 3%. PMID- 2232577 TI - [Vagotomy in emergency surgery of complicated duodenal ulcer]. AB - The article deals with general information on the immediate and late-term results of operations with vagotomy for perforating and bleeding duodenal ulcers in 670 patients. Indications for economical operative interventions in emergency situations were determined. The immediate and late-term results of economical operations with vagotomy allow them to be recommended for introduction into wide surgical practice. PMID- 2232578 TI - [Treatment of patients with perforated gastroduodenal ulcer]. AB - The immediate results of treatment of 114 patients with perforating gastroduodenal ulcer were analysed. The causes of late hospitalization and late operations and their effect on postoperative complications and mortality are discussed. Preference is given to closure of the perforation with sutures (108 patients); closure of the perforation with creation of a gastroentero-anastomosis was carried out in 3 and primary resection of the stomach in 3 more patients. Complications occurred in the immediate postoperative period in 8 patients (7%), which were due either to late admission to the hospital or to delayed operative intervention. The postoperative mortality rate was 7%. Early hospitalization and early operative intervention are the real means of improving the results of treating patients with perforating gastroduodenal ulcer. PMID- 2232579 TI - [Prevention of dumping syndrome after distal gastrectomy in peptic ulcer]. AB - Operations were performed on 386 patients with peptic ulcer by a method suggested by the authors for gastric resection with formation of a sphincter in the region of the anastomosis. In 18 patients a Billroth II anastomosis was reconstructed into a Billroth I anastomosis by the authors' modification in severe dumping syndrome. Complex examination was conducted in late-term postoperative periods in 324 patients after primary resection and in 18 after reconstructive operation. A mild dumping syndrome was found in 9 (2.8%) and 3 patients, respectively. The results of the study show that if the authors' requirements regarding the volume and method of gastric resection are abided by, there is no doubt that the suggested method has advantages over the classical method in that the reservoir function of the stomach is maintained, hydrochloric acid secretion reduces to a state of hypo- or normoacidity, and the peristaltic component of evacuation is preserved due to the formed functionally active anastomosis. PMID- 2232580 TI - [Anterior seromyotomy of the body and the functional part of the stomach combined with posterior truncal vagotomy and ulcer excision in the surgical treatment of complicated stomach ulcer]. AB - Anterior seromyotomy of the body and fundus of the stomach was combined with posterior truncal vagotomy and excision of the ulcer in 23 patients with gastric ulcer complicated by bleeding or perforation. Seventeen patients had chronic ulcers of the body of the stomach (type I), 3 patients had concurrent ulcers (type II), and 3 more patients had acute ulcers of the body of the stomach. Operation was undertaken for active bleeding from the ulcer in 20 patients and for perforating ulcer in 3 patients. One patient died. Mild disorders of evacuation of an aqueous barium sulfate suspension from the stomach were noted in 4 patients. PMID- 2232581 TI - [Surgical tactics in bleeding duodenal ulcers]. AB - The article gives a review of literature on the determination of surgical tactics in patients with duodenal ulcer complicated by bleeding. The authors are supporters of the actively-temporizing tactics. They claim that the period of the delay in the decision should not exceed 24 hours and depends on the intensity of the bleeding, the degree of blood loss, the location and nature of the ulcer, the patient's age, and the concomitant diseases. They believe resection of the stomach to be the operation of choice in bleeding duodenal ulcer. One of the authors suggested a modified method of gastric resection in "difficult" duodenal ulcers which excludes the occurrence of incompetence of the duodenal stump sutures. PMID- 2232582 TI - [Clinico-morphological parallels in Mallory-Weiss syndrome]. AB - The article deals with the results of treatment of 180 patients with the Mallory Weiss syndrome. Morphological studies of the gastric wall was conducted in 16 patients who underwent operation. It was established that developmental anomalies, chronic gastritis, and pathological changes of the vessels of the lamina muscularis mucosae impairing its mobility and strength may be the morphological substrate which precedes the development of the Mallory-Weiss syndrome. PMID- 2232583 TI - [Clinico-roentgenological diagnosis of dumping syndrome in expert medical evaluation of work capacity]. AB - The authors conducted complex clinical and X-ray examination of 80 patients suffering from the dumping syndrome of various degree. They were sent to the Central Scientific Research Institute of Expert Medical Assessment of Working Capacity for establishing the degree of severity of morphological and functional disorders affecting their capacity for work. The method of examination of such patients, including X-ray and other clinical methods, is described. The main clinical and roentgenosemeiotic signs characteristic of the mild, moderately severe, and severe forms of the dumping syndrome are pointed out. Clinical cases are described in illustration of the diagnostic possibilities and the expert approach to the results of the examination of such patients. PMID- 2232584 TI - [Pathogenetic aspects of the treatment of diffuse suppurative peritonitis]. AB - Experience with the treatment of 130 patients with generalized purulent peritonitis is analysed. The complex of therapeutic measures included intraoperative cleansing of abdominal cavity with ultrasound; postoperative prolonged laparoscopic cleansing with the use of rational antibacterial therapy and laser irradiation of the abdominal cavity. The cell immunity values in patients with peritonitis were studied and the principles of immunocorrective therapy substantiated. It is shown that detoxification measures are necessary in the treatment of this category of patients. A complex approach to the treatment of purulent peritonitis led to a decrease in mortality to 13.8%. PMID- 2232585 TI - [Hemosorption in the complex treatment of patients with suppurative peritonitis of appendicular etiology]. AB - Analysis of the results of treatment of 240 patients with generalized peritonitis of appendicular origin showed that the application of hemosorption led to noticeable and stable diminution of intoxication in 84% of cases. In the ++post sorption period, the severity of endotoxicosis did not change essentially in 12% of cases and increased in the remaining cases. The therapeutic effect of hemosorption was found to be unstable in patients with signs of multiple organ insufficiency developing in prolonged poorly effective therapy as well as in patients with unrecognized abdominal abscesses, incompetence of the sutures of anastomoses, thrombosis of the mesenteric vessels, and early intestinal obstruction due to adhesions. Endotoxicosis intensified during hemosorption in patients with extensive epifascial phlegmons. It is proved that hemosorption applied repeatedly in the early postoperative period with due account for the individual features of the course of the disease ensures an optimal therapeutic effect. PMID- 2232586 TI - [Metabolic function of the liver in middle-aged and elderly patients with peritonitis]. AB - From analysis of experimental (576 rats) and clinical (104 patients) materials, the authors drew the conclusion that the pharmacological activity of certain drugs metabolized in the liver increased markedly in old rats with experimental peritonitis. The drug-metabolizing function of the liver was inhibited significantly in peritonitis in elderly and senile patients. A method was developed for establishing the stages of peritonitis. PMID- 2232587 TI - [Toxemia syndrome in patients with acute intestinal obstruction]. AB - The results of examination and treatment of 216 patients with acute intestinal obstruction of benign genesis are discussed. The values of blood plasma toxicity and the values of hemostasis determined before and after the operation were compared. Intoxication of patients was found to increase in the postoperative period. Its increase was appraised according to the duration of the disease. The causes of mortality were analysed and the risk factors of intoxication increase in the postoperative period were revealed. The authors suggest a classification of the phases of intoxication in patients with acute intestinal obstruction on the basis of the degree of intoxication and the condition of homeostasis. PMID- 2232588 TI - [Carcinoid tumor of the appendix]. AB - The authors discuss data in the literature and analyse the features of the clinical picture, diagnosis, and treatment of carcinoid of the vermiform process in 8 patients. The late-term results are shown. PMID- 2232589 TI - [Use of dalargin in complex anesthesiological protection during operations on the abdominal organs]. AB - The authors analyse experience in the use of the synthetic analogue of ++leu enkephalin dalargin in multicomponent balanced anesthesia in operations on the abdominal organs in 36 patients. With the use of the suggested method the intraoperative expenditure of narcotic analgesics is 6 times less but the efficacy of the anesthesia remains the same. Study of the activity of the liver specific enzymes (histidase and urokinase) in blood plasma and biopsy material taken from the liver and the content of malonic dialdehyde in the hepatic biopsy specimen revealed hepatoprotective properties of dalargin. The decrease of the total peripheral resistance and increase of the elasticity of the arterial reservoir++ in the main group as compared to these values in patients treated by the traditional method were considered by the authors to be the consequence of the autonomic priming effect of the opiopeptide used. It is concluded that the use of synthetic analogues of endogenous opioids (dalargin) in the anesthesiological protection complex in operations on the abdominal organs is expedient. PMID- 2232590 TI - [Characteristics of the course of gastroduodenal ulcer and its surgical treatment in elderly patients]. AB - The authors analyze in detail the literature on the subject and the results of treatment of 234 patients over 60 years of age. It is confirmed that peptic ulcer in elderly and old-aged individuals has some specific features. The mortality rate after planned surgical interventions for gastric and duodenal ulcer in patients over 60 years was 5.0% and 3.9%, respectively. Emergency surgical interventions for complications of peptic ulcer at old age led to death in 44.4% and 50% of cases, respectively. It is concluded that the range of indications for planned and earlier surgical treatment of peptic ulcer in the elderly must be widened. PMID- 2232591 TI - [Combined surgical operations in the abdominal cavity and retroperitoneal space]. AB - The authors discuss their experience in combined operations on the organs of the abdominal cavity and retroperitoneal space in 366 patients whose ages ranged from 16 to 81 years. In 96 patients (26.2%) the operations were carried out for emergency indications and in 270 (73.8%) in a planned order. The authors substantiate the expediency of performing combined operations by a low mortality rate (1.9%) (in carrying out the operations separately the mortality rate comes up to 15%) and by an economical effect. PMID- 2232592 TI - [Selection of the method of treatment of complicated hemorrhoids]. AB - The authors make a comparative analysis of the immediate complications after hemorrhoidectomy conducted by various methods in 504 patients engaged in heavy physical work. Group 1 consisted of 172 patients with hemorrhoidectomy performed by the ligature method. Group 2 was made up of 151 patients who had been operated on by A. N. Ryzhikh's modification of Martynov's method. Group 3 included 145 patients treated by the Milligan-Morgan operation involving the restoration of the anal mucosa. Group 4 consisted of 36 patients who had undergone ligation of the terminal branches of the superior rectal artery with economical excision of the hemorrhoids. In appraisal of the results of operative treatment of hemorrhoids, the least number of complications were found in patients of groups 3 and 4. PMID- 2232593 TI - [Treatment of patients with bleeding hemorrhoids]. AB - The article discusses the choice of the optimal therapeutic tactics, the volume of preoperative examination, and the rational techniques of surgical treatment in 65 patients with profuse bleeding from the hemorrhoids. It is shown that digital examination, proctosigmoidoscopy, as well as adequate examination of the whole large intestine must be undertaken without fail in this group of patients. Assessment of the volume of blood loss, its correction under hemoglobin control, and consideration for the patient's general condition allows radical operative treatment to be conducted in the majority of cases (96.4%). Good results were produced with the use of advanced surgical techniques of hemorrhoidectomy. PMID- 2232594 TI - [Surgical treatment of cancer of the large intestine, complicated by intestinal obstruction]. AB - Retrospective analysis of the treatment of 3,080 patients with cancer of the large intestine made it possible to distinguish compensated, sub- and decompensated degrees of the neoplastic stenosis and place the two last named into the category of a complicated course of cancer. In subcompensated stenosis (complications in 16.3% of cases, mortality 5.9%), irrespective of the location of the tumor, the authors consider one-stage intervention with primary restoration of the continuity of the intestine to be the operation of choice. In decompensated stenosis (complications 28.9%, mortality 13.2%) caused by tumors of the right colon and the rectum they recommend a similar policy, while in tumors of the left colon they believe Hartmann's operation to be indicated. PMID- 2232596 TI - [Morbidity and mortality in anesthesia]. PMID- 2232595 TI - [Clinical course and treatment of traumatic rectal fistula]. AB - From experience in treatment of 104 patients with rectal fistulas of traumatic origin the authors distinguished the specific features of the clinical manifestations of the disease which must be taken into consideration in choosing the therapeutic tactics. In contrast to the management of common chronic paraproctitis, the treatment of traumatic rectal fistulas differs in principle, particularly when the internal opening of the fistula is in the wall of the rectal ampulla++. The authors determined the indications for various methods of treatment and techniques of operative interventions, including multistage surgical treatment with the creation of temporary colostomy. PMID- 2232598 TI - [Avoidance of positioning-induced damage]. PMID- 2232597 TI - [Notes on safety in anesthesia. Part 1: human and technical errors]. PMID- 2232599 TI - [Quantifying volume loss]. PMID- 2232600 TI - [Stabilization of the perioperative heat balance]. PMID- 2232601 TI - [Safety-relevant characteristics of infants and young children]. PMID- 2232602 TI - [Avoiding technical complications in epidural conduction anesthesia]. PMID- 2232603 TI - [An analysis of anesthetic incidents from the medical point of view]. PMID- 2232604 TI - [Avoiding technical complications in peripheral nerve blocks]. PMID- 2232605 TI - [Safety of the anesthesia breathing equipment]. PMID- 2232606 TI - [Dosage equipment, concentration monitoring and the anesthesia system]. PMID- 2232609 TI - [An analysis of anesthesia incidents from the legal point of view]. PMID- 2232607 TI - [Detection and avoidance of disconnections in the breathing system]. PMID- 2232608 TI - [Reliability and error possibilities in monitoring]. PMID- 2232610 TI - [Measures for the prevention of infections in anesthesia]. PMID- 2232611 TI - [Reliability of infusion systems and equipment]. PMID- 2232613 TI - [Training in medical technological equipment]. PMID- 2232612 TI - [Prevention of electric accidents and electric injuries]. PMID- 2232614 TI - [Computer simulation of anesthesia and anesthesia-related incidents]. PMID- 2232615 TI - [Decision support]. PMID- 2232616 TI - [The critical incident conference as an instrument of quality control]. PMID- 2232618 TI - [Organizing and equipping the workplace]. PMID- 2232617 TI - [Teaching methods in continuing education]. PMID- 2232619 TI - [Qualitative and quantitative personnel planning]. PMID- 2232620 TI - [Quality assurance through organizational measures]. PMID- 2232621 TI - [Risk minimization in arterial and venous catheterization]. PMID- 2232622 TI - [Intubation and the avoidance of its risks]. PMID- 2232623 TI - [Lessening the aspiration risk]. PMID- 2232624 TI - New approaches in the treatment of the dystonias. AB - At this point the treatment of dystonias remains highly empirical. Secondary dystonias, especially those related to specific drug treatment, have to be ruled out carefully. A few dystonic subgroups respond well to levodopa medication. In the other syndromes, anticholinergics are the usual first choice. In focal conditions botulinum toxin injections seem to be the most effective regimen, although there are only a few long-term studies. Surgical procedures are an ultimate option. PMID- 2232625 TI - The influence of penbutolol and placebo on blood sugar levels and insulin consumption in the glucose-controlled insulin infusion system ("artificial endocrine pancreas"). AB - The aim of the study was to investigate the influence of 40 mg of the beta blocker penbutolol (Betapressin TM; Hoechst Ltd., Frankfurt/Main) in comparison to placebo on the insulin consumption on the blood sugar profile in twelve insulin-dependent diabetes (IDDM) patients. The patients were treated with penbutolol and placebo for a period of three days, and then were examined with the help of the glucose-controlled insulin infusion system. The blood sugar profile and insulin consumption over a 24 hour period was not affected by either penbutolol or placebo, nor could any changes be measured in these parameters when measured after food intake. After a submaximal exercise load on the bicycle ergometer (1 watt per kg body weight) following an evening meal, no difference could be observed between penbutolol and placebo in the above-mentioned parameters. The same was also true for hormonal parameters as STH, ACTH, cortisol, and catecholamines. These findings demonstrated that medication of penbutolol over a three-day period has no influence on the baseline blood sugar profile and insulin consumption or on insulin consumption after food intake during rest and physical exercise. PMID- 2232626 TI - Gastric emptying in non-responders to H2-receptor antagonists. AB - H2-receptor antagonists are known to fail to increase the intragastric pH in some patients (so-called non-responders), and we have recently found a higher frequency of non-responders among cirrhotics. Since intragastric pH is also affected by gastric emptying, in the present study we determined the gastric emptying of 300 ml orange juice labelled with [99mTc]-Solco Nanocoll using a gamma camera. Measurements were made over a period of 60 min in cirrhotic patients and controls without liver disease who either responded to 300 mg ranitidine or showed no response. The mean (+/- SD) liquid half-emptying time (T1/2) was 26.3 +/- 17.5 min (range, 9-75 min) in responders (n = 10), 20.9 +/- 8.6 min (range, 7-34 min) in non-responders (n = 10), 19.4 +/- 19.2 min (range, 7 75 min) in cirrhotics (n = 11), and 27 +/- 4.6 min (range, 17-33 min) in controls (n = 9). In 19 of the 20 subjects gastric emptying was normal (T1/2, less than 40 min). Since gastric emptying was not delayed in any of the non-responders, it would appear very unlikely that gastric motility plays a major role in the non response to H2-receptor antagonists. PMID- 2232627 TI - [The role of TSH psychological and somatic changes in thyroid dysfunctions]. AB - The characteristic psychic and somatic features found in patients with overt hyper- or hypothyroidism are usually attributed to elevated or diminished levels, respectively, of thyroid hormones. This concept does not sufficiently explain our previous investigations in which the same symptoms, albeit attenuated, were also seen in patients suffering from so-called latent disturbances of thyroid function. This state of disorder, however, exhibits normal concentrations of peripheral thyroid hormones. Only the response of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone (TRH) stimulation is in accordance with the behaviour of the overt thyroid dysfunction and enables its differentiation from the euthyroid state. In this context, we investigated the question as to whether pathologic signs in thyroid disorders are correlated to alterations of peripheral thyroid hormones or to changes in the hypothalamus pituitary axis. Therefore, we investigated two groups of ten patients each who suffered from latent hyper- or hypothyroidism, respectively, and ten euthyroid controls. All were matched from sex and age. Endocrine function was estimated by TRH testing, TT3, TT4 and thyroxine binding globulin (TBG). Psychologic testing was performed by questionnaires concerning subjective somatic symptoms, emotional disturbances, psychomotoric performance, cognitive impairment and personality. Patients with latent hyperthyroidism were more subject to somatic symptoms and affective complaints than were those who had latent hypothyroidism. As compared with controls, there were significant differences in exhaustion and pain in the limbs and heart. In terms of affective complaints, patients were more depressive, anxious, touchy and irritable; their personalities showed a higher degree of emotional lability, excitement and irritability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232628 TI - Acute tubulo-interstitial nephritis with uveitis (TINU syndrome) in a patient with serologic evidence for Chlamydia infection. AB - A 38-year-old female patient with acute tubulo-interstitial nephritis and uveitis (TINU syndrome) is described. The cause of this rare disease is unknown; most patients affected are adolescent females. Serologic investigations in the patient reported point to a possible etiologic role of Chlamydia infection in this disease. PMID- 2232630 TI - Concurrent hypercortisolism and hyperaldosteronism due to an adrenal adenoma. AB - The case of a 39-year-old woman with Cushing's syndrome, hypertension and severe hypokalemia, caused by a unilateral adrenal adenoma composed of cells of the zona fasciculata histological type, is described. Plasma renin activity, plasma levels of mineralocorticoids and the aldosterone secretion rate were determined before and after surgical removal of the adenoma. The tumor appeared to produce autonomously cortisol as well as corticosterone, 18-hydroxycorticosterone and aldosterone. This condition has not previously been described in the literature and might be explained by strong expression of the full spectrum of activities of the mitochondrial enzyme P450 C11 by the tumor cells. Interestingly, despite hyperaldosteronism, plasma renin activity was not suppressed. PMID- 2232629 TI - Successful therapy of meningococcal sepsis in acute disseminated lupus erythematosus with plasmapheresis, immunosuppression, and antibiotics. AB - A 17-year-old female with a 5-year history of disseminated lupus erythematosus has remained without immunosuppressive therapy for the last 3 years. She was admitted to the hospital for acute abdominal pain, generalized edema, and rapidly developing dyspnea and somnolence. Although all symptoms were consistent with active SLE, septicemia was suspected because of leukocytosis (20,000/microliters), greatly elevated C-reactive protein (45 mg/dl), and normal complement values (C3 0.74 g/l, C4 0.21 g/l). Directly after bacterial blood cultures were prepared, a combined treatment was instituted consisting of plasmapheresis (3 x 2.1 l against fresh frozen plasma), antibiotics, prednisolone, and cyclophosphamide following the last plasmapheresis. Within three days cerebral function returned to normal, edema improved, and CRP fell to 0.5 mg/dl. The blood cultures and pericardial effusion displayed meningococcal colonies. PMID- 2232631 TI - Studies on proteolysis of protein kinase C with calpain I and II. AB - Earlier reports from this laboratory have shown that protein kinase C (PKC) is cleaved with Ca2(+)-dependent neutral protease (calpain) I or II to produce a catalytically active fragment, and that calpain I, which is active in the micromolar range of Ca2+, may react preferentially with the active form of PKC that is associated with membranes. Subsequently, PKC is shown to exist as a large family of multiple subspecies with subtle individual characteristics. Three types of PKC designated types I, II, and III are purified from rat brain cytosol, which are shown to correspond to the cDNA clones gamma, beta, and alpha, respectively. The aim of the present study was to characterize the proteolysis of each PKC subspecies with calpain I and II. All types of PKC (82 kDa) were converted to two major fragments: a 47-49-kDa catalytic and a 36-kDa regulatory fragments by the cleavage with either calpain I or II. Analysis of the NH2-terminal sequence of the resulting catalytic fragments indicated that both calpain I and II cleaved at one or two specific sites in the variable region (V3) of each PKC molecule of which structure was clearly different among PKC subspecies. From kinetic studies, the cleavage of PKC subspecies with calpain I, and to a lesser extent, with calpain II (active in the millimolar range of Ca2+), was remarkably enhanced by the simultaneous presence of phospholipid and diacylglycerol or phorbol ester, suggesting that the active forms of PKC subspecies were the preferred targets for proteolysis. Whereas, stimulatory abilities of the lipids were variable among PKC subspecies and inactive form of type I PKC was cleaved with calpain I at a significant rate. Quantitative analysis with a fixed amount of calpain under comparable conditions showed that the susceptibilities of the PKC subspecies were distinctly different one another; the relative rates of cleavage of types I, II, and III PKC with calpain I and II were approximately 100:16:2 and 100:48:23, respectively. These results indicated that within the cell various PKC subspecies might be cleaved at different rates under different physiological conditions. PMID- 2232632 TI - [Chemotherapy of epilepsy (review of foreign literature)]. PMID- 2232633 TI - [Ultrasonic diagnosis of liver diseases]. AB - Sonography has become widely used in the diagnosis of liver diseases. Fatty infiltration of the liver (adiposis hepatica), hepatic cirrhosis, cysts, metastases and tumors can be reliably diagnosed. A valid differentiation between benign and malignant new growths, however, can only be obtained by cytologic and histologic techniques. The lowest sensitivity can be expected in chronical benign diffuse diseases. Our results were compared with those in literature. Furthermore, other diagnostic approaches and procedures, e.g. fine needle biopsy and sclerotherapy in cysts, are recorded. PMID- 2232634 TI - [Recurrent meningococcal meningitis]. PMID- 2232635 TI - [A case of Wissler-Fanconi allergic subsepsis syndrome]. PMID- 2232636 TI - [A case of skin amyloidosis in an elderly patient]. PMID- 2232637 TI - [Selection of therapeutic tactics for nonspecific spontaneous hemopneumothorax]. AB - The results of treatment have been analyzed for 45 patients with nonspecific spontaneous hemopneumothorax. Therapeutic policy was decided upon individually basing on the patient's condition and clinical appearance of the disease. Urgent surgery was performed in 68.0% of patients for continuous intrapleural bleeding and tense pneumothorax. The rest cases underwent pleural puncture. Pleural drainage failed to eliminate spontaneous hemopneumothorax in all the patients. The causes of SHP were established mostly intraoperatively. In 81.8% of the cases it resulted from a rupture of a bullous lung. Long-term follow-up (1-18 years) of 28 patients treated surgically and conservatively recorded no recurrences. PMID- 2232638 TI - [Family physician: problems and realities]. AB - The experience gained in the Soviet Union and abroad with family physician service is reviewed. The scope of his duties is outlined which are to be adjusted for specific conditions of rural and city health care. The family physician is to be neither a particular specialist nor an expert in all fields of medicine, rather a broad-minded and skilled internist informed about social and psychological matters and able to attend both adults and adolescents. The chief goal of his practice should be prophylaxis medicine, regular check-ups. Extensive experimental research is needed to adopt the system of family physician in this country as it necessitates revision of conventional principles of industrial, school, outpatient services, training of medical staff, etc. PMID- 2232639 TI - [The first in Russia center of higher medical education (on the 280th anniversary of the Moscow hospital and the Moscow medico- surgical school--the S.M. Kirov Military Medical Academy)]. PMID- 2232640 TI - [S.P. Botkin and the St. Petersburg Society of Russian Physicians (biographical data)]. PMID- 2232642 TI - [Intravascular coagulation in acute and chronic hepatitis]. PMID- 2232641 TI - [Medical observations in A.P. Chekhov's novel "From Siberia"]. PMID- 2232643 TI - [Chronic enteropathies]. PMID- 2232644 TI - [Respiratory infections as a risk factor for patients with ischemic heart disease]. AB - The effect of respiratory infection (influenza, parainfluenza, adenovirus and enterovirus) on clinical and functional states was assessed for coronary (n-850) and noncoronary (n-250) patients. The infection-related pathology turned out more severe in coronary patients. Disaggregation agents were found useful in early diagnosis of coronary heart disease and prevention thereof. PMID- 2232645 TI - [Comparative value of electrocardiographic criteria of myocardial ischemia in exercise tests]. AB - Treadmill and isometric tests were carried out in 108 patients with coronary heart disease confirmed at coronary arteriography versus 51 healthy subjects. Among myocardial ischemia criteria depressed S-T segment came out as most reliable (probability of valid diagnosis greater than 90%), less significant was wave T inversion, wider wave R amplitude, painful syndrome (probability 70%). The rise and depression of oblique upward segment S-T, abnormal T amplitude proved inferior to the above signs (probability less than 50%). To achieve valid diagnosis of coronary heart disease and to assess its severity, exercise tests should produce reliable criteria of myocardial ischemia. PMID- 2232646 TI - [Variants of the clinical course of ventricular pre-excitation syndrome]. PMID- 2232647 TI - [Difficulties in the diagnosis of rheumatic heart defects in elderly patients]. AB - Clinical and autopsy data presented in this paper illustrate difficulties arising in diagnosis of rheumatic heart disease (RHD) in elderly patients. RHD misdiagnosis is explained by unclear clinical symptoms, undone laboratory tests, concomitant diseases, misinterpretation of some objective indications (auscultatory symptoms, ECG). To diagnose acquired RHD earlier the physicians are recommended to refer their patients to ultrasound investigations of the heart. PMID- 2232648 TI - [Esophageal diseases in patients with stenocardia and angiographically changes and little-changed coronary arteries]. AB - Angiography conducted in 29 anginal patients has shown that coronary arteries were intact in 23 and little affected in 6 of them. Signs of myocardial ischemia were recorded at myocardial scintigraphy, bicycle ergometry, 24-h ECG monitoring in 17 patients. Esophageal lesions confirmed by endoscopy, manometry, esophageal pH-metry with Bernstein test were revealed in 20 examinees (68%). It is suggested that patients with persistent chest pain and unaffected coronary arteries who are resistant to antianginal therapy should undergo functional study of the esophagus including endoscopy, manometry and pH-metry. PMID- 2232650 TI - [Evaluation of the effectiveness of calcium antagonists combined with digoxin and furosemide in hypertension complicated by circulatory insufficiency in elderly patients]. AB - Clinical, hemodynamic and neurohumoral data are available supporting the validity of a differentiated approach to administration of combined treatment with furosemide, digoxin and calcium antagonists nifedipine and verapamil in advanced aged patients with hypertension complicated by circulatory disorders. The choice of the drugs should be based on the criterion of per hour diuresis following a single dose of the combination. PMID- 2232649 TI - [Laser acupuncture in the complex treatment of stenocardia]. AB - Acupuncture points were exposed to helium-neon laser beam in 200 anginal patients. This therapeutic modality yielded good results: the number of attacks and nitroglycerin intake reduced, exercise tolerance grew, echocardiographic evidence showed a positive trend, hemodynamics improved, Spilberger's test values changed for the better. PMID- 2232651 TI - [Clinical value of 24-hour monitoring of arterial blood pressure using a portable apparatus]. PMID- 2232652 TI - [Evaluation of the effect of intravenous administration of streptodecase on the extent of the damage in myocardial infarction]. AB - Precordial mapping was employed to examine 29 patients with acute anterior transmural myocardial infarction (MI). Seventeen of them received intravenous streptokinase, eleven underwent symptomatic therapy. The size of the lesion was assessed in the course of the disease. It is shown that streptokinase administration within the initial 6 hours of MI promotes arrest of the ischemic lesion augmentation and eventually diminishes the area of MI. PMID- 2232653 TI - [Use of dynamic transesophageal electric stimulation of the heart in patients with functional disorders of the sinoatrial node]. AB - Transesophageal pacing used for sinus dysfunction detection in 103 patients has been assessed for informative appropriateness in design of the attendance policy and efficacy of outpatient chemotherapy. The response control by electrophysiological monitoring was performed in 22 patients with true sick sinus syndrome (group 1) and 27 ones with sinus dysfunction (group 2). The rest patients were not controlled objectively. Transesophageal pacing of 5 group 1 patients brought about indications for surgical treatment. For 8 patients the follow-up revealed evolution of the sinus vegetative dysfunction into organic lesion which required surgical intervention in one case. The effect of chemotherapy with sympathomimetic drugs in adequate doses tended to reduction with increasing duration of the follow-up. In those with true sick sinus syndrome this process ran more actively. Long-term chemotherapy for sinus dysfunction is found effective as it warrants appreciable improvement of sinoatrial conduction, outpatient therapy control by dynamic transesophageal pacing is objective and can be recommended as adequate. PMID- 2232654 TI - [Effectiveness of long-term antihypertensive therapy with tenoretic--a combined long-acting drug]. PMID- 2232656 TI - [Diagnosis of drug intolerance]. PMID- 2232655 TI - [Status of microcirculation in patients with ischemic heart disease and concomitant bronchopulmonary diseases]. AB - Microcirculation was studied by bulbar biomicroscopy in 111 coronary patients (105 males and 6 females) treated at sanatorium. Eighty-three of them exhibited concomitant bronchopulmonary impairment: chronic obstructive, chronic nonobstructive bronchitis and bronchial asthma in 40, 36 and 7 patients, respectively. The combined effect of the diseases leading to mutual aggravation has an adverse sequelae in terminal circulation, which can be managed by therapeutic impact on cardiorespiratory system. Special measures aimed at better ventilation result in microcirculatory improvement and should be included into rehabilitation programs for patients with cardiorespiratory pathology. Such patients are recommended to undergo microcirculation study which would be able to indicate the condition severity and serve a criterion of sanatorium treatment effectiveness. PMID- 2232657 TI - [Evaluation of the quality of drug therapy of middle-aged and elderly patients]. PMID- 2232658 TI - [Neurologic disorders in insulinoma]. AB - Three cases of insulinoma-related neuropsychic disturbances and literature data are considered. Special emphasis is given to polymorphism of epileptiform syndrome, concomitant disphoric paroxyms and lethargy. A case of a rare syndrome coma vigil is described in the advanced stage of the disease. The discussion covers pathogenetic mechanisms and differential diagnosis. PMID- 2232660 TI - [Computerized tomo-myelography in the diagnosis of lesions of the spinal cord]. PMID- 2232659 TI - [Effect of the treatment on hemodynamic indicators and plasma testosterone level in patients with juvenile hypertension]. AB - The effect of anapriline, corinfar and reserpine on parameters of hemodynamics and plasma testosterone was evaluated in 60 juvenile hypertension patients who achieved pronounced hypotensive response. It was established that the level of sex hormones tended to diminution by the end of the treatment month 1 or 2, this drop being more noticeable in reserpine administration. Basing on this evidence it would be beneficial for patients suffering from juvenile hypertension in need of chemotherapy to take courses of the above drugs. PMID- 2232661 TI - [Liver abscesses with intrathoracic complications]. PMID- 2232662 TI - [The masks of violence]. PMID- 2232663 TI - [Don't wait until it is too late]. PMID- 2232665 TI - [Report from Italy. A little piece of humanity]. PMID- 2232664 TI - [Health education for shelter seekers. Values to respect]. PMID- 2232666 TI - [Atomic energy: an abuse of creation]. PMID- 2232667 TI - [The body language of the soul]. PMID- 2232668 TI - [Promotion of urinary continence in hospitalized aged: a worthwhile expenditure]. PMID- 2232670 TI - [Voluntary re-entry--involuntary exit. Changes undesirable]. PMID- 2232669 TI - [Visit in a cooperative for the aged. "We maintain a high grade of culture in our dialogue"]. PMID- 2232671 TI - [A working day in a small private hospital. "Like a film that is running too fast"]. PMID- 2232672 TI - [Health for all: talking about it and doing it. . ]. PMID- 2232673 TI - [Poor and sick in a rich country?]. PMID- 2232674 TI - [Disturbed nutritional behavior--psychological problems?]. PMID- 2232675 TI - [Transplantation: the 2 faces of progress]. PMID- 2232676 TI - [Man--a piece of merchandise?]. PMID- 2232677 TI - [Medico-ethical guidelines for transplantation]. PMID- 2232678 TI - [Transplantation: emotionally we are left behind]. PMID- 2232679 TI - [The viewpoint of a patient with liver transplantation. "The new liver is feeling fine in my body"]. PMID- 2232680 TI - [The operating room nurse's viewpoint. "We would like to transplant more"]. PMID- 2232681 TI - [Organ transplantation in Switzerland]. PMID- 2232682 TI - [Bone marrow transplantation]. PMID- 2232684 TI - [Organ removal. What is going on in the operating room?]. PMID- 2232683 TI - [Community nurses are cooperating in a regional program of health promotion: prevention of "heartbreakers"]. PMID- 2232685 TI - [3 practitioners talk about grafts. Love of the profession]. PMID- 2232686 TI - [The childrens' problem: refusing the lie]. PMID- 2232687 TI - [Stress, questioning, subtlety--from the donor to the transplant patient: a difficult passage]. PMID- 2232688 TI - [Organization and coordination. Programs for organ exchange]. PMID- 2232689 TI - [Profile of a patient with liver transplantation and the course of care: looking for a better method of care]. PMID- 2232691 TI - [Report from Italy: a little humanity]. PMID- 2232690 TI - ["Learning happiness". Interview by Francoise Taillens]. PMID- 2232692 TI - [Refuse in the hospital]. PMID- 2232693 TI - [Refuse disposal in the hospital. 2. Practical refuse disposal in clinical practice]. PMID- 2232694 TI - [Recycling of disposable materials is objectionable from medical, legal, economic and ecologic viewpoints]. PMID- 2232695 TI - [Ways of artificial fecal diversion]. PMID- 2232696 TI - [Colorectal cancer]. PMID- 2232697 TI - [Ambulatory care is better and less expensive]. PMID- 2232698 TI - [Changes in health care delivery--new perspectives for ambulatory patient care]. PMID- 2232699 TI - [Postoperative confusion in aged patients]. PMID- 2232700 TI - [Freedom]. PMID- 2232701 TI - Extracellular matrix biosynthesis by cultured fetal rat lung epithelial cells. II. Effects of acute exposure to epidermal growth factor and retinoic acid on collagen biosynthesis. AB - The effects of acute exposure to epidermal growth factor (EGF), retinoic acid, and EGF + retinoic acid on collagen biosynthesis by fetal rat lung epithelial (FRLE) have been evaluated. Acute exposure to either EGF or retinoic acid resulted in a small increase in the amount of radioactive substrate incorporated into total proteins, but simultaneous exposure to EGF + retinoic acid increased total protein synthesis approximately 2-fold. Quantitative evaluation of the genetic types of collagen synthesized by FRLE cells (types I, III, IV, and V) revealed that each experimental condition affected collagen production in a different manner. Acute exposure to EGF selectively inhibited type III collagen production, minimally affected type I and type IV collagen synthesis, but enhanced type V collagen production. Acute exposure to retinoic acid minimally affected type III production but slightly enhanced the synthesis of type I molecules. Simultaneous acute exposure to both EGF and retinoic acid significantly increased the amounts of types I, IV, and V collagen synthesized but minimally affected type III collagen production. Evaluation of the molecular forms of type I collagen (the type I-heterotrimer-molecular composition [alpha 1 (I)]2 alpha 2(I) and the type I-homotrimer-molecular composition [alpha 1 (I)]3) synthesized under each condition revealed that EGF minimally affected the production of either molecular form of type I collagen. In contrast, acute exposure to retinoic acid in the absence or presence of EGF caused a greater than 2-fold increase in the amount of type I-homotrimers synthesized but substantially decreased the amount of type I-heterotrimers produced. These results demonstrate that alone, either EGF or retinoic acid modulate collagen synthesis by FRLE cells and that in combination, these substances exert effects on collagen production that differ from their individual actions. Thus, in addition to documenting that EGF and retinoic acid modulate collagen biosynthesis in a cell line derived from the fetal type II pneumocyte, these studies establish that FRLE cells constitute a useful in vitro model system for investigating the regulation of matrix biosynthesis and its relationship to the development of the alveolar epithelial cell. PMID- 2232703 TI - Fate of nerve fibers in necrotic, healing, and healed rat myocardium. AB - Myocardial infarction, myocardial scar tissue formation, and cardiac arrhythmogenesis seem to be associated. There are electrophysiological data suggesting that myocardial nerves are involved in arrhythmia development; however, there are no morphologic studies describing the fate of these nerves following necrotizing myocardial injuries. To describe the reactions of Schwann cells and axons following such injuries, we induced lesions in rat hearts with ischemia or transdiaphragmatic freeze-thawing and examined the acutely necrotic, healing, and healed lesions with light and electron microscopy. Antibodies to Schwann cell-associated S-100 protein were used to facilitate histologic detection. Both forms of injury produced focal lesions in which Schwann cells were killed and axonal segments destroyed; however, the basal lamina sheaths of cardiac myocytes and capillaries, and probably also of nerve fibers, remained largely intact. During 4 weeks of sequential observations, Schwann cells and axons were components of a hypercellular healing front that began at the periphery and moved toward the center of each lesion. Their proliferation and growth may have occurred within the original nerve basal lamina sheaths, and reparative axonal enlargements contained an abundance of 50- to 100-nm clear and dense storage granules. Fully developed nerve fibers were not only present in newly formed scar tissue but also appeared to be present in significantly greater density than in uninjured myocardial tissue. These findings demonstrate that proliferative nerve fiber regeneration occurs from the edges of necrotizing myocardial injuries, that healing results in relatively large number of nerve fibers in newly formed scars, and that axons in these scar-associated nerve fibers contain an abundance of neurosecretory granules. The functional significance of these observations remains to be determined. PMID- 2232702 TI - Two rat models of hepatic fibrosis. A morphologic and molecular comparison. AB - We present a morphologic and molecular comparison of two models of hepatic fibrosis. Immune complexes are the source of insult in one model. In the other model, CCl4 induces fibrosis. For the immune complex model, rats were immunized intraperitoneally over the course of 4 weeks with human albumin, then injected through a tail vein three times a week for at least 5 more weeks with the same albumin. Seventy-five percent of all treated animals developed fibrosis characterized by fine collagen bands. There was a mild degree of hepatocyte trapping and necrosis as well as some bile duct hyperplasia and tissue eosinophilia. However, there was no significant Kupffer cell hyperplasia or inflammatory reaction. Quantification of specific mRNA species was determined by Northern blot hybridization analysis of total RNA. In comparison with CCl4 induced fibrosis in rats, a hepatotoxin-mediated model with a much greater inflammatory response, this immune complex model showed a less pronounced increase in type I procollagen mRNA, but a relatively greater increase in types III and IV procollagen mRNA. Whereas transforming growth factor-beta 1 mRNA levels were markedly increased in CCl4-induced fibrosis, there was only a slight increase in this cytokine, known to stimulate type I collagen synthesis, in the immune complex model. A comparison of the two model systems indicates that a variety of mechanisms may be involved in the process of hepatic fibrogenesis. It appears that an inflammatory response and elevated transforming growth factor beta 1 levels are associated with a marked increased synthesis of type I collagen in a hepatotoxin model while other, as yet undefined, mediators may be responsible for the increase in types III and IV procollagen mRNA species found in the immune complex model. PMID- 2232705 TI - Smooth muscle differentiation in cultured human breast gland stromal cells. AB - We analyzed in cultures from the human breast the potential of stromal cells resembling fibroblasts to undergo smooth muscle differentiation. The cellular components of the breast tissue from 10 biopsies were disaggregated by collagenase digestion and further purified by differential centrifugation into suspensions of single cells and intact blood vessels. These two fractions of stromal cells were plated in culture and their phenotypic traits analyzed within 24 hours. During this time, the blood vessel fraction gave rise to stromal cells with smooth muscle differentiation as judged immunocytochemically using monoclonal antibodies to alpha-/gamma-muscle actins, to alpha-smooth muscle actin, to type IV collagen, and to laminin. Furthermore, the cells of this fraction resembled smooth muscle cells based on 2D gel electrophoresis and immunoblotting determination of isoactin content. After 24 hours in culture, the single-cell fraction consisted of an almost pure population of cells not exhibiting smooth muscle differentiation but rather resembling fibroblasts. Maintenance of fibroblast-like cells without smooth muscle differentiation was possible for more than 14 days on chemically defined medium. These cells remained quiescent, as measured by cell quantification and immunoreactivity to the proliferation-associated antigen, Ki-67. Growth of these cells could be stimulated by adding serum at any time during the experimental period. Single cell fractions from seven biopsies were allowed to grow exponentially in the presence of serum for up to 10 days, and the kinetics of smooth muscle differentiation were monitored immunocytochemically and biochemically. These experiments showed that alpha-smooth muscle actin synthesis was induced in 10 to 80% of the fibroblast-like cells after 4 to 11 days in culture. Both the final number of alpha-smooth muscle actin-positive cells and the onset of synthesis varied with the initial seeding density. Dose-response experiments (at constant cell density) revealed that serum exerted maximal effect at concentrations above 10%. It was therefore concluded that elements of smooth muscle differentiation may arise in non-smooth muscle stromal cells taken directly from human breast tissue. PMID- 2232704 TI - Propylthiouracyl-induced hypothyroidism results in reversible transdifferentiation of somatotrophs into thyroidectomy cells. A morphologic study of the rat pituitary including immunoelectron microscopy. AB - Two-month-old female Fischer-344 rats were rendered hypothyroid by ingestion of propyl-thiouracyl (PTU) (0.1% in drinking water) and sacrificed 3, 7, 14, and 28 days after the start of PTU administration as well as 3, 7 and 14 days after interruption of a 14-day PTU treatment. Controls received no PTU. The pituitaries were studied by histology, immunohistochemistry, electron microscopy, and immunoelectron microscopy, using the immunogold double-labeling technique. In the course of hypothyroidism, pituitary thyrotrophs had undergone the well-known thyroidectomy change. In addition, a contingent of growth hormone (GH) cells lost their large secretory granules, enlarged, displayed progressive dilation of rough endoplasmic reticulum, thereby transforming into thyroidectomy cells. These bihormonal thyrosomatotrophs contained gH in their secretory granules and thyrotropin in the dilated rough endoplasmic reticulum as documented by the immunogold double-labeling method for GH and thyrotropin. After discontinuation of PTU treatment, a rapid increase in size, number and GH labeling of secretory granules and simultaneous involution of distended rough endoplasmic reticulum with reduction of thyrotropin labeling took place in thyrosomatotrophs. A practically complete restitution of normal pituitary structure was seen in 2 weeks. Results implicate that, contrary to previously accepted concepts, adenohypophysial cells may not be irreversibly committed to one morphologically recognizable cell line. PMID- 2232706 TI - Inherited lysozyme deficiency in rabbits. The absence of a primary isozyme of lysozyme as the cause of the condition. AB - Lysozyme from normal and genetically lysozyme-deficient rabbits was extracted from three types of tissue: leukocytic (bone marrow), lymphoepithelial (thymus and appendix), and gastrointestinal (colon). Extracts were analyzed by electrophoretic, chromatographic, and kinetic techniques. Identification of at least two isozymes of rabbit lysozyme was made with these techniques. The distribution of the isozymes was tissue specific. Leukocytic and gastrointestinal isozymes were clearly distinguished, and a possible lymphoepithelial isozyme that resembled the gastrointestinal isozyme electrophoretically and chromatographically but not kinetically was identified. Mutant, lysozyme deficient rabbits lacked completely a detectable leukocytic isozyme but had gastrointestinal and lymphoepithelial isozyme(s) indistinguishable from those of normal rabbits. By electrophoretic methods, the mutant rabbits were demonstrated to lack a protein band corresponding to that of the leukocytic isozyme of lysozyme from normal rabbits. These observations considered collectively were interpreted as evidence that at least two primary isozymes of lysozyme are present in rabbits and that inherited lysozyme deficiency in rabbits is caused by the absence of a single primary isozyme. PMID- 2232707 TI - Photoaffinity labeling of human c-myc protein with deoxythymidine triphosphate. AB - The recombinant human c-myc protein expressed in Escherichia coli can be efficiently labeled by ultraviolet-mediated cross-linking to dTTP and to a lesser extent to other nucleoside diphosphates and triphosphates, but not to nucleoside monophosphates. Specificity of nucleoside phosphate binding is suggested by (a) concentration-dependent competition by some nucleoside phosphates but not by others and (b) by the observation that the denatured myc protein does not bind the nucleotides. Competition experiments also indicate that the affinity of c-myc protein for nucleoside diphosphates and triphosphates is approximately the same irrespective of the nature of the base, or of the pentose sugar, but the thymine base permits the most efficient photoactivated cross-linking. The ultraviolet mediated photoactivated cross-linking of deoxythymidine triphosphate has been used to identify the c-myc protein in extracts of cells which overexpress c-myc, and to identify the intermediates in myc oncoprotein degradation. PMID- 2232708 TI - A novel diagnostic method of Pneumocystis carinii. In situ hybridization of ribosomal ribonucleic acid with biotinylated oligonucleotide probes. AB - The reactivity and specificity of the in situ hybridization of ribosomal RNA in the diagnosis of Pneumocystis carinii were investigated. Three complementary oligonucleotide probes, 22 and 25 nucleotides long, corresponding to the species specific regions of 5S and 18S ribosomal RNA of Pneumocystis carinii were synthesized and labeled with biotinylated dUPT at the 3' termini. In situ hybridization was performed on formalin-fixed paraffin-embedded human lung tissues using the mixture of these probes and detected with the avidin-biotin peroxidase complex method. The reactions were positive in all 12 cases of Pneumocystis carinii pneumonia, but in none of the infections with other pathogenic agents, including virus (6 cases), mycobacteria (4 cases), protozoa (4 cases) and fungi (8 cases). The reactivity and specificity of this method was comparable with that of immunohistochemistry using a monoclonal anti-human Pneumocystis carinii antibody. Because the specificity of in situ hybridization is based on nucleotide sequences of ribosomal RNAs, that are constant among species, contrary to morphology of protista or expression of antigens, it should complement conventional staining and immunohistochemical methods, and provide a useful tool for the diagnosis of Pneumocystis carinii. PMID- 2232709 TI - Human MCTC type of mast cell granule: the uncommon occurrence of discrete scrolls associated with focal absence of chymase. AB - Two types of mast cells were previously defined based on neutral protease composition and ultrastructurally distinguished by granule morphology. The MCT cell contains tryptase with little, if any, chymase and was noted to have varying numbers of irregularly-shaped granules with discrete scrolls or particulate or beaded material. The MCTC cell contains both tryptase and chymase and was noted to have more regularly-shaped electron-dense granules with characteristic grating or lattice substructures. This study reports the use of electron microscopy and immunogold staining with antibodies against tryptase and chymase to demonstrate in mature unstimulated MCTC cells in situ, the focal occurrence of discrete or complete scrolls in peripheral regions of certain granules where chymase is deficient. these scrolls often appeared to be protruding from the granule. Granules containing discrete scrolls were observed in 10 of 340 mature MCTC cells, accounting for less than 1% of MCTC granules. Other granules in such cells as well as other regions of the granule under consideration, showed strong staining for both tryptase and chymase. These results strengthen the association of morphology with protease composition in human mast cell secretory granules, but weaken the use of morphology alone to identify the MCTC and MCT types of human mast cells. Whether the uncommon occurrence of focal absence of chymase in MCTC cells arises by chance or as a result of factors relating to mast cell development, interconversion, activation, or regranulation will require further clarification. In conclusion, the appearance of grating or lattice structures in mast cells indicates the presence of chymase and tryptase, characteristic of the MCTC phenotype, whereas multiple discrete scrolls in irregularly shaped granules suggests the MCT phenotype. PMID- 2232711 TI - Heparan sulfate proteoglycans in amyloidogenesis: an epiphenomenon, a unique factor, or the tip of a more fundamental process? PMID- 2232710 TI - Amyloid enhancing factor and inflammatory reaction. PMID- 2232712 TI - Determinants of immune cell trafficking in the skin. PMID- 2232713 TI - localization of type VI collagen in the lining cell layer of normal and rheumatoid synovium. AB - Types I to VI collagens were immunolocalized in normal and rheumatoid synovium using monospecific antibodies. Immunofluorescence studies showed type VI in the extracellular matrix of the lining cell layer, whereas positive staining for type III collagen was observed in both the lining and sublining cell layers. All other collagens could not be detected in the lining cell layer. Immunogold staining of the rheumatoid synovium localized type VI collagen to filamentous material, which was the major extracellular structure of the lining cell layer. Type III collagen was associated with thin cross-striated collagen fibrils. A brief treatment of rheumatoid synovial tissue with bacterial collagenase produced in the lining cell layer numerous broad-banded fibrils with 100-nm periodicity; these fibrils could be labeled with the antibody against type VI collagen. This suggests that type VI collagen filaments have the potential to form periodic structures under certain conditions. We further studied the susceptibility of type I to VI collagens to matrix metalloproteinase 1, 2 and 3 (collagenase, gelatinase of molecular weight 72,000, stromelysin), which are secreted by synovial lining cells in rheumatoid synovium, and found only type VI collagen to be completely resistant to all these metalloproteinases. These data indicate that type VI collagen, which has the ability to bind to cells and to interstitial collagens, plays an important role in supporting the synovial lining cells in the normal and rheumatoid synovium. PMID- 2232714 TI - Increased production of tumor necrosis factor by normal immune cells in a model of the humoral hypercalcemia of malignancy. AB - The rat Leydig cell tumor is a well characterized model of the humoral hypercalcemia of malignancy. The studies reported here were provoked by the observation that tumor-bearing rats become extremely cachectic and develop hypertriglyceridemia as they become hypercalcemic. Since the bone resorbing cytokine tumor necrosis factor (TNF)/cachectin is associated with cachexia and hypertriglyceridemia, we examined hypercalcemic tumor-bearing rats for evidence of increased TNF production using a TNF radioimmunoassay. We found that immunoreactive TNF was increased in the plasma of tumor-bearing rats. The increase in plasma TNF was comparable to that previously shown in hypercalcemic nude mice bearing Chinese hamster ovarian cell tumors transfected with the human TNF gene. There was no detectable TNF activity in tumor culture media which suggested that the tumor itself was not the source of excess TNF production. However, we found that tumor cell conditioned media enhanced the production of TNF activity by normal macrophages in vitro, indicating that increased TNF production in vivo may result from a tumor factor(s) which stimulates TNF production by normal immune cells. When TNF was added together with tumor products to organ cultures of fetal rat long bones, osteoclastic bone resorption was potentiated. These data are consistent with the concept that in this model of the humoral hypercalcemia of malignancy, increased TNF production by normal immune cells is increased, has systemic effects as suggested by cachexia and hypertriglyceridemia, and may work in concert with factors produced directly by tumor cells to overwhelm normal calcium homeostasis. PMID- 2232715 TI - Expression of native and deglycosylated colon cancer mucin antigens in normal and malignant epithelial tissues. AB - Immunohistochemical techniques were used to determine the distribution and cellular location of the mature and precursor forms of a colonic-type mucin in normal and malignant epithelial tissues. The antisera used in this study were prepared against native human colon cancer mucin (LS), partially deglycosylated mucin (HFA or GalNAc-apomucin), and fully deglycosylated mucin (HFB or apomucin). These antisera reacted with most mucin-producing cells of the normal gastrointestinal tract, salivary ductular cells, bronchial epithelial cells, some bronchial mucous glands, and squamous epithelial cells of the esophagus. Breast, endometrium, ovary, prostate, liver, and thyroid were nonreactive. In most normal organs, HFB reactivity was present in the supranuclear and perinuclear cytoplasm and LS and HFA were located primarily in goblet cell vacuoles, apical cytoplasm, and luminal secretions. These findings are consistent with the expected subcellular locations of apomucin and more "mature" mucins. LS, HFA, and HFB were frequently expressed in adenocarcinomas of the colon, stomach, pancreas, and lung. Lymphoma, sarcoma, and melanoma specimens were nonreactive. Alterations in the expression of these mucin antigens in malignant tissues included loss of subcellular compartmentalization, increased intensity of staining, and disappearance of staining. In addition, de novo expression of HFB was observed in one of five breast carcinomas and three of five ovarian mucinous cystadenocarcinomas. These data demonstrate that LS, HFA, and HFB are useful for studying the organ specificities and biosynthetic pathways of one type of mucin in normal and malignant tissues. PMID- 2232717 TI - The checkerboard tissue block. An improved multitissue control block. AB - We describe an improved method of embedding a large number of tissue samples in a single, normal-sized paraffin block. Because the tissues are evenly distributed in a checkerboard arrangement, they can be readily identified by their position in the resulting sections. This device permits rapid and inexpensive screening of new histologic reagents, and facilitates intra- and interlaboratory quality control. PMID- 2232716 TI - Effects of reduced dietary magnesium on platelet production and function in hamsters. AB - The increased vulnerability of animals fed a magnesium (Mg)-deficient (MD) diet to ischemia-induced myocardial necrosis has been attributed to changes in myocardial electrolyte metabolism. However, a variety of hematologic changes have also been reported in MD and some of these, such as an increase in platelet aggregability, may contribute to the increased myocardial vulnerability. In the present study, we quantified the effect of MD on platelet and megakaryocyte abundance as well as on platelet aggregability with and without an administered calcium channel blocker (nifedipine). Hamsters were fed either a "minimal Mg" diet, in which the level of Mg was kept just high enough to prevent seizures, or a "preset Mg" diet containing precisely known amounts of Mg. Animals fed the minimum Mg diet showed an initial increase in the platelet count, which returned to control range when the dietary Mg was increased to 9 mmoles/kg. Animals on the preset Mg diet showed an increased platelet count if the Mg level was 10 mmoles/kg or less. In addition to the increase in number, platelets from MD animals were less responsive to the aggregation-inhibiting effect of nifedipine than were platelets from control animals, although MD itself did not result in an increased aggregability under the conditions used here. Animals with an increase in circulating platelets showed decreased megakaryocyte abundance in the femoral marrow, but megakaryocytes that were present were larger than those in control animals. These results indicate a profound effect of dietary Mg deficiency on platelet biology. The observed changes could contribute to the increase in myocardial vulnerability to injury found in MD animals. PMID- 2232718 TI - Clearance of IgA in patients with IgA nephropathy. PMID- 2232719 TI - Cocaine in pregnancy: confronting the problem. PMID- 2232720 TI - Cocaine use and effect: a major perinatal risk factor in the nineteen nineties. PMID- 2232721 TI - A modification of the PEG technique. PMID- 2232722 TI - Complications of augmentation mammaplasty and their treatment. PMID- 2232723 TI - Cocaine abuse in pregnancy--a myriad of unanswered questions. PMID- 2232724 TI - Breast augmentation--is there a risk? PMID- 2232725 TI - Living wills and the identification bracelet. PMID- 2232726 TI - South Carolina medicine fifty years ago. PMID- 2232727 TI - Guidelines for HIV and AIDS student support services. PMID- 2232728 TI - Developmentally-based AIDS/HIV education. AB - A growing number of health and education professionals argue that AIDS/HIV education curricula should be developmentally-based. They suggest the principles of developmental psychology be used to design curricula based on the sequentially ordered ways children of different ages understand AIDS. Relying on findings of research on development of children's conceptions of illness, a specific developmentally-based approach to educating school-age children about AIDS/HIV is presented in this paper. For each of three major age groups, the paper describes general characteristics for children's thought processes, ways in which children assimilate information about various aspects of AIDS, and implications for educating children about causes, prevention, and fear of AIDS. The focus of AIDS/HIV education can move from reducing fear in the younger group, to identifying and differentiating causes and noncauses of AIDS in the intermediate groups, to articulating strategies for AIDS prevention in the older group. PMID- 2232729 TI - AIDS/HIV education for preservice elementary teachers. AB - Professional preparation programs should provide future elementary teachers opportunities to develop competence in dealing with school-related AIDS issues. Curriculum writers and instructors of preservice elementary teachers could be more effective if they were aware of this groups' beliefs about school-related AIDS issues. A survey was conducted to assess the beliefs and opinions of preservice elementary teachers about school-related AIDS issues. Subjects (n = 157) generally agreed they would eventually have a child with AIDS in their classroom and agreed AIDS education should be included in the elementary grades, yet a substantial number did not believe they understood the basics about AIDS. Less than one-third indicated they knew how to clean up blood or body fluids safely. About one-third indicated they would feel personally threatened to teach a student with AIDS. These results are reflected in recommended AIDS educational content and resources for preservice elementary teachers and future research in this area. PMID- 2232730 TI - A professional preparation course on AIDS/HIV infection. AB - This paper describes the conceptualization, development, planning, and implementation of a new professional preparation course entitled "AIDS/HIV Education: Issues and Strategies." The 15-week, campuswide course was offered through the Dept. of Health Science Education at the University of Florida during spring semester 1990. Though universities have been identified as providers of preservice education for future teachers and health professionals, current activities often have been deemed inadequate to meet the needs of those charged with providing AIDS/HIV education. This course was implemented to address an array of issues related to HIV education, ranging from epidemiological and biomedical information and educational strategies to examination of personal and ethical issues surrounding the disease. Delivery of a successful course and student reaction are discussed, along with recommendations for programs considering similar educational efforts. A detailed planned information packet is available from the authors. PMID- 2232731 TI - Differences in AIDS knowledge and attitudes by grade level. AB - Grade-related similarities and differences in AIDS knowledge and attitudes were assessed in 441 fifth, seventh, and tenth graders from one school district. Grade level was a significant variable (p less than .01) on 53% of items. Grade-related differences in knowledge were apparent when students responded to questions tapping information not covered widely in the media and in attitudes when personal engagement in behavior was implied. Cognitive and emotional factors related to developmental milestones were postulated to account for these differences. These findings need to be considered in planning and implementing AIDS prevention programs, especially as education is begun for younger children. PMID- 2232732 TI - A comparison of AIDS and STD knowledge between sexually active alcohol consumers and abstainers. AB - Effective curricula should influence knowledge levels of all students, including high-risk populations. In this study, a modified version of the National Adolescent Student Health Survey was administered to a group of eighth and 10th grade students (N = 3,803) exposed to a curriculum designed to improve AIDS and STD knowledge levels. The analysis examined the influence of gender, ethnicity, alcohol use, and sexual activity as they related to AIDS and STD knowledge. Findings indicated poor knowledge scores on STD items, with no significant differences on group comparisons. Comparisons of AIDS knowledge scores indicated significant differences based on gender, ethnicity, and behavior. Females scored higher than males, whites scored higher than blacks, and abstainers from sexual activity and alcohol scored higher than their active counterparts. Results suggest current educational efforts are not equally effective. Future educational initiatives should be sensitive to group membership. PMID- 2232733 TI - HIV-related knowledge and behaviors among high school students--selected U.S. sites, 1989. PMID- 2232734 TI - HIV risk continuum. PMID- 2232735 TI - Impact of television news exposure on children's perceptions of violence in Northern Ireland. AB - The present study assessed the impact of television news exposure on Irish children's perceptions of the level of violence in their neighborhoods. Estimates from children (N = 570) of the local levels of violence in three areas (high-, low-, and no-violence) were subjected to a four-way analysis of variance (Area x Sex x Age x News Exposure) that showed a main effect for area and sex with respect to the high-violence area and boys. Two two-way interactions also reached statistical significance. The first suggested that the perception of lower levels of violence by girls was confined to the high- and low-violence areas. The second concerned the level of actual violence and the amount of reported news exposure. Only in the high-violence area were these two variables related: Accurate estimates of actual violence levels were associated with more frequent news exposure. PMID- 2232736 TI - Perceived intimacy of expressed emotion. AB - Research on norms for emotional expression and self-disclosure provided the basis for two hypotheses concerning the perceived intimacy of emotional self disclosure. The first hypothesis was that the perceived intimacy of negative emotional disclosure would be greater than that of positive emotional disclosure; the second was that disclosures of more intense emotional states would be perceived as more intimate than disclosures of less intense emotional states for both negative and positive disclosures. Both hypotheses received support when male students in Canada rated the perceived intimacy of self-disclosures that were equated for topic and that covered a comprehensive sample of emotions and a range of emotional intensities. The effects were observed across all the topics of disclosure examined. PMID- 2232737 TI - Grouping students for instruction: effects of learning style on achievement and attitudes. AB - The present study examined the effects of matching and mismatching American middle-school students with a preference for learning alone or learning with peers with selected instructional treatments in order to determine the impact upon their attitudes and achievement in social studies. Analysis revealed that the learning-alone preference performed significantly better in the learning alone condition and that the learning-with-peers preference performed significantly better in the learning-with-peers condition. However, no-preference students also performed significantly better in the learning-alone condition than with peers. In addition, data revealed that the learning-alone and the learning with-peers students had significantly more positive attitudes when matched with their preferred learning style; the nopreference students had more positive attitudes in the learning-alone condition. PMID- 2232738 TI - Social support as a moderator of the relationship between poverty and coping behavior. AB - This study examined the relationship between poverty and coping and defense behaviors and the way social support moderates this relationship. One hundred fifty Indian adults responded to scales of income, perceived economic status, coping, defense and social support. In addition, physical quality of living was rated on the basis of observation and a short interview. Results showed that income and physical quality of living were positively associated with perceived economic status. Income, physical quality of living, and perceived economic status were negatively related to coping and defense behaviors. Finally, social support did not moderate the impact of poverty on coping and defense behaviors. PMID- 2232739 TI - Belief in a just world and attitudes toward AIDS sufferers. PMID- 2232740 TI - Effect of transient mood state on the self-serving bias. PMID- 2232742 TI - Who shall be called language disordered? Some reflections and one perspective. AB - This paper discusses some issues involved in identifying children who have language problems. The perspective taken is that (a) the goal of identification must be clearly distinguished from other goals of assessment; (b) identification of children with language disorders is better based on language performance than on inferences about the language knowledge that underlies this performance; (c) language performance must be sampled in more than one context, including, for purposes of identification, contexts that stress the language system; (d) the standards of expectations for comparing performance and determining differences must be explicit; (e) standards used to determine differences are better based on the performance of chronological-age peers than on the performance of children with similar mental abilities; and (f) children who do not evidence poor language performance but are considered at risk for language-related problems should be distinguished from children who demonstrate poor language skills. PMID- 2232741 TI - Taxonomies in biology, phonetics, phonology, and speech motor control. AB - This article begins with a review explaining the different purposes of biological taxonomies. Taxonomic units are often dependent on the purpose for which the taxonomy has been constructed. Biological taxonomies provide an analogy that we use to emphasize some of the distinctions among the units of phonetic transcription systems, competence phonologies, and performance phonologies. The units of both phonology and phonetic transcription are considered as possible units of the speech motor system, and some of the difficulties of this assumption are explained. Although phonemic units, like units of phonetic transcription, are useful for many purposes, it is not theoretically necessary to use units derived as part of competence phonologies in systems attempting to explain phonological performance or speech motor performance. In this regard, we challenge the concept of coarticulation, because it is based on assumptions about the role of phonological or phonetic units in speech motor control. We offer an integrated perspective that has implications for research in speech motor control and deficits of the speech motor system. We see speech motor deficits as distinct from, yet possibly interacting with, phonological deficits. PMID- 2232743 TI - Effects of repair strategies on visual identification of sentences. AB - This investigation determined whether information elicited by repair strategies enhances an individual's ability to lipread a misperceived sentence. Five groups of subjects were each assigned one of five repair strategies: (a) asking the talker to repeat a sentence, (b) simplify it, (c) rephrase it, (d) say an important keyword, and (e) speak two sentences. Subjects viewed sentences spoken by six different talkers. When a subject did not recite a sentence verbatim, the talker performed the assigned repair strategy and then repeated the original sentence. A control group of subjects saw only the original sentence repeated twice. All five test groups demonstrated a significantly greater improvement for the second presentation score (referenced to the first presentation score) than the control group. The benefits provided by the repair strategies were independent of the talker, and benefits did not differ significantly among the groups. PMID- 2232744 TI - Spoken and written English errors of postsecondary students with severe hearing impairment. AB - This investigation compared the spoken and written English errors of 20 hearing impaired postsecondary students with intelligible speech and poor English language. Error categories used to assess the language samples were function, content, and structure. Spoken and written performances were distinguished only by a greater number of function word errors in writing samples. A trend toward greater complexity in writing was also found. Implications for instruction are discussed. PMID- 2232745 TI - Tabletop versus microcomputer-assisted speech management: response evocation phase. AB - This is the third in a series of studies on the use of microcomputers with speech delayed children. Two repeated-measures designs (n = 15) and five case studies were completed to compare tabletop management at early and late stages of the response development phase with two comparable, computer-assisted drill-and practice activities. Discrimination of correct articulatory responses was mediated by the clinician in all modes, rather than by speech recognition hardware, but all contingent reinforcement in the computer modes was presented by animation graphics. The two computer modes were identical except for the addition of fantasy involvement in one of the modes. Findings indicated that the three modes of intervention were equally effective, efficient, and engaging. Subject level analyses suggested that microcomputer software has excellent potential to engage children in drill-and-practice for late-phase response evocation, when the target sound is stimulable, but limited usefulness with young children at early phase response evocation, when specific articulatory behaviors need to be cued. Discussion considers learning, child, and hardware/software factors in microcomputer-assisted speech management. PMID- 2232746 TI - The relationship between communication problems and psychological difficulties in persons with profound acquired hearing loss. AB - Communication strategies, accommodations to deafness, and perceptions of the communication environment by profoundly deaf subjects were correlated with indices of psychosocial adjustment to determine whether accommodations to deafness could play a role in the presence of psychological difficulties among deaf persons. Persons with postlingually acquired profound deafness were administered the Communication Profile for the Hearing Impaired (CPHI) and several standardized tests of psychological functioning and adjustment. Inadequate communication strategies and poor accommodations to deafness reported on the CPHI were associated with depression, social introversion, loneliness, and social anxiety. Limited communication performance at home and with friends was related to both social introversion and the experience of loneliness; perceived attitudes and behaviors of others correlated with depression as well as loneliness. In general, the pattern of correlations obtained suggests that specific communication strategies and accommodations to deafness, rather than deafness per se, may contribute to the presence of some psychological difficulties in individuals. PMID- 2232747 TI - Generalized learning of receptive and expressive action-object responses by language-delayed preschoolers. AB - This study examined the effectiveness of matrix-training procedures in teaching action + object utterances in both the receptive and expressive language modalities. The subjects were 4 developmentally delayed preschool boys who failed to produce spontaneous, functional two-word utterances. A multiple baseline design across responses with a multiple probe technique was employed. Subjects were taught 4-6 of 48 receptive and 48 expressive responses. Acquisition of a word combination rule was facilitated by the use of familiar lexical items, whereas subsequent acquisition of new lexical knowledge was enhanced by couching training in a previously trained word combination pattern. Although receptive knowledge was not sufficient for the demonstration of corresponding expressive performance for most of the children, only minimal expressive training was required to achieve this objective. For most matrix items, subjects responded receptively before they did so expressively. For 2 subjects, when complete receptive recombinative generalization had not been achieved, expressive training facilitated receptive responding. The results of this study elucidate benefits to training one linguistic aspect (lexical item, word combination pattern) at a time to maximize generalization in developmentally delayed preschoolers. PMID- 2232748 TI - Generalization to conversational speech. AB - Although changes in children's phonological systems due to treatment have been documented in single-word testing, changes in conversational speech are less well known. Single-word and conversation samples were analyzed for 10 phonologically disordered children, before and after treatment and 3 months later. Results suggest that for most of the children, there were system changes in both single words and in conversational speech. It appears that many phonologically disordered children are able to extend their correct production to conversation without direct treatment on spontaneous speech. PMID- 2232749 TI - Comprehension monitoring in language-disordered children: a preliminary investigation of cognitive and linguistic factors. AB - This study provided a preliminary investigation of the relative influence of cognitive and communicative factors in comprehension monitoring. This question was approached by studying language-disordered (LD) children for whom these abilities are presumably dissociated. Their performance on an ambiguity detection task was compared to that of two groups of control children, one matched for comprehension level and the other for cognitive level. Results revealed that LD children performed similarly to the control children who were matched for level of comprehension. The LD children's performance was examined along a continuum of the relative influence of cognitive and communicative factors, given that neither type of factor alone could sufficiently account for effective comprehension monitoring. It was concluded that communicative factors, both active primary comprehension and social communicative knowledge, had a stronger influence than the cognitive factors in our particular comprehension monitoring task. PMID- 2232750 TI - Verbal behaviors of preschool stutterers and conversational partners: observing reciprocal relationships. AB - Standard counseling practices with the families of young stutterers include recommendations that listeners' negative verbal behaviors be modified in order to reduce the likelihood of stuttering. This study tested the hypothesis that stuttering and normal disfluencies in preschool stutterers are related to selected verbal behaviors in conversational partners. Twelve 2- to 6-year-old stutterers were video recorded while playing with their mother, father, and a familiar peer. The resulting videotapes were transcribed and two types of social communicative analyses (total number of words and utterances, verbal intent of the speaker) were undertaken. Results suggested that fathers used more words and utterances than mothers and peers. Parents provided more positive interactions with their stutterer offspring than did peers. Parents also asked significantly more negative and routine questions when talking to their stuttering child. Peer playmates were significantly more negative and generally commented more frequently when interacting with stutterers than did the parents. Stutterers were involved in significantly more positive interactions with their fathers. The frequency of fluency failures did not differ significantly when stutterers communicated with their mother, father, or peer partners. Implications regarding verbal styles of partners in relationship to the stuttering of preschool children are discussed. PMID- 2232751 TI - Aphasic and non-brain-damaged adults' descriptions of aphasia test pictures and gender-biased pictures. AB - Twelve aphasic and 12 non-brain-damaged adult males described the speech elicitation pictures from the Boston Diagnostic Aphasia Examination (BDAE), the Minnesota Test for Differential Diagnosis of Aphasia (MTDDA), the Western Aphasia Battery (WAB), and six pictures representing male-biased or female-biased daily life situations. For each speech sample we calculated number of words, words per minute, number of correct information units, percentage of words that were correct information units, and percentage of correct information units that were nouns or adjectives (amount of enumeration or naming). The WAB picture elicited more enumeration than the BDAE or MTDDA pictures, and information was produced at a slower rate in response to the WAB picture than the other two pictures. These differences were statistically significant and appear to be clinically important. Gender bias had statistically significant effects on two measures. Male-biased pictures elicited significantly more words and significantly more correct information units than female-biased pictures. However, these differences were small and do not appear to be clinically important. Two of the five measures (words per minute and percentage of words that were correct information units) differentiated non-brain-damaged speakers from aphasic speakers. The magnitude of these differences suggests that these measures provide clinically important information about the problems aphasic adults may have when they produce narrative discourse. PMID- 2232752 TI - Impairment of speech intelligibility in men with amyotrophic lateral sclerosis. AB - Speech intelligibility was studied in a group of 25 male patients with amyotrophic lateral sclerosis (ALS). The object of the study was to determine the phonetic impairments underlying the speech intelligibility deficits that frequently accompany ALS. Analyses with a word intelligibility test indicated that the most disrupted phonetic features involved phonatory (voicing contrast) function, velopharyngeal valving, place and manner of articulation for lingual consonants, and regulation of tongue height for vowels. The mean error proportion for the five most severely affected features correlated highly (0.97) with the intelligibility score (percent correct). The phonetic feature analyses are one index of bulbar muscle impairment in amyotrophic lateral sclerosis and also may help to direct the speech management in these individuals. PMID- 2232753 TI - Facilitating changes in supervisees' clinical behaviors: an experimental investigation of supervisory effectiveness. AB - This research was conducted to determine whether supervisees altered their clinical behaviors as a consequence of a joint data-analysis method of clinical supervision. Four beginning graduate student clinicians assigned to articulation clients were supervised in accordance with tenets of Cogan's Clinical Supervision Model and Anderson's Continuum of Supervision. Supervision focused on the targeted dependent variables of clinician "explanations," "informative feedback," and "directive responses to off-task utterances." Visual inspection of multiple baseline data indicated that target behaviors improved after they became the focus of supervision. The supervisory procedures implemented in this study effected positive changes in the supervisees' clinical behaviors. Qualitative discoveries that relate to the practicalities of daily supervision are discussed. PMID- 2232754 TI - Patient compliance with cleft palate team regimens. AB - A cleft palate team's prescribed regimen requires prompt and continued compliance in order to meet the management objective and to justify the large investment of professional time. The purposes of this clinical investigation were to determine the rate of compliance with the recommendations made by a cleft palate team for its patients and to identify variables associated with compliance. A subject was defined as the person(s) who could best respond to questions concerning the management of the team's patient. Each subject was interviewed using a questionnaire. The mean patient compliance rate was 64.4%, and noncompliance with specific recommendations ranged from 12.5% to 100%. Using Jones and Caldwell's (1981) classification, 17.1% of the patients were classified as compliers, 78% as partial compliers, and 4.9% as noncompliers. The best predictor of compliance was a set of nine variables. PMID- 2232755 TI - A sindscal analysis of perceptual features for consonants produced by esophageal and tracheoesophageal talkers. AB - This study was concerned with the perceptual responses of normal-hearing listeners to consonants produced by esophageal and tracheoesophageal (TE) talkers and a single talker who was proficient in both of these alaryngeal speech modes. The listeners' perceptual responses were analyzed using Symmetric Individual Differences Scaling (SINDSCAL) to determine whether distinctive feature differences existed between these two methods of alaryngeal speech. This a posteriori analysis revealed that primary features retrieved for both speech methods included sibilant, affricate, dental, nasal, and sonorant. Although greater perceptual weightings were observed for TE speech, these productive/perceptual features were weighted similarly for both speech methods. Some secondary group-specific feature differences were also observed, but these features did not contribute substantially to the total amount of variance accounted for in the analysis. Thus, the SINDSCAL results showed that the groups did not use different feature systems. These results are discussed in regard to the unique alaryngeal speech production methods employed by esophageal and TE talkers and the relative limitations of the alaryngeal (esophageal) voicing source they use. General clinical implications of the data are discussed. PMID- 2232756 TI - Normative data in quiet, broadband noise, and competing message for Northwestern University Auditory Test No. 6 by a female speaker. AB - Two descriptive experiments were performed on a version of the Northwestern University Auditory Test No. 6 (NU No. 6) recorded by a female speaker that is included on an audio compact disc recently produced by the Department of Veterans Affairs. In Experiment 1, normative psychometric functions for the female speaker version of the NU No. 6 materials were established on 24 young adults for three monaural listening conditions (in quiet, in 60-dB SPL broadband noise, and in 60 dB SPL competing message). The 60-dB SPL broadband noise shifted the psychometric function for the NU No. 6 words 33 dB, whereas the 60-dB SPL competing message shifted the function only 18-22 dB. In contrast to the slopes of the quiet and noise conditions (4.5%/dB), the slope of the competing message function was more gradual (3.5%/dB). In Experiment 2, comparisons between the psychometric functions for the female and the original male speaker versions of NU No. 6 in quiet and in broadband noise were made on 8 young adults. In comparison to the psychometric functions for the male speaker version of NU No. 6, the functions for the female speaker version of NU No. 6 were displaced between the 10-90% correct points to higher sound-pressure levels by 10-13 dB in quiet and by 12-16 dB in noise. The difference in performance on the two versions of NU No. 6 is attributed to spectral differences between the two sets of materials that produced a calibration anomaly. PMID- 2232758 TI - Comment on "Concomitant speech and language disorders in stuttering children: a critique of the literature". PMID- 2232757 TI - The Iowa Articulation Norms Project and its Nebraska replication. AB - The purpose of the Iowa Articulation Norms Project and its Nebraska replication was to provide normative information about speech sound acquisition in these two states. An assessment instrument consisting of photographs and a checklist form for narrow phonetic transcription was administered by school-based speech language pathologists to stratified samples of children in the age range 3-9 years. The resulting data were not influenced by the demographic variables of population density (rural/urban), SES (based on parental education), or state of residence (Iowa/Nebraska); however, sex of the child exerted a significant influence in some of the preschool age groups. The criteria used to determine acceptability of a production appeared to influence outcomes for some speech sounds. Acquisition curves were plotted for individual phoneme targets or groups of targets. These curves were used to develop recommended ages of acquisition for the tested speech sounds, with recommendations based generally on a 90% level of acquisition. Special considerations were required for the phonemes /ng s z/. PMID- 2232759 TI - Comment on "Methodological variables affecting phonational frequency range in adults". PMID- 2232760 TI - Genetic implications of gender differences in the prevalence of spontaneous otoacoustic emissions. AB - Spontaneous otoacoustic emissions (SOAEs), which occur in about 40% of normal hearing humans, do not have a firm explanation in auditory theory nor are their distributional properties well understood. To enhance our understanding of SOAEs, we have pooled data from three reports (Hammel, 1983; Strickland, Burns, & Tubis, 1985; Zurek, 1981) to assemble a large enough sample to assess the relevant hypotheses about the effects of ear and gender on their presence. The results, based on loglinear analyses of the pooled sample of 131 normal-hearing subjects, indicated that (a) the prevalence of SOAEs for female subjects [P(S/F) = .533] was significantly higher than that for male subjects [P(S/M) = .268]; (b) the percentage of right ears with SOAEs (36.6%) was significantly greater than that of left ears (25.2%); and (c) right and left ears were not independent with respect to the presence of SOAEs. These results can be explained by assuming that the (a) tendency to exhibit emissions is inherited, perhaps as a sex-linked trait and (b) ears are asymmetric with respect to the anatomical anomalies of the apical portion of the organ of Corti that may precipitate SOAEs. PMID- 2232761 TI - A comparison of psychometric functions for detection in normal-hearing and hearing-impaired listeners. AB - Psychometric functions (PFD) for the detection of pure tones were obtained with a two-interval forced-choice procedure from a group of listeners with normal hearing and a group of listeners with sensorineural impairments of presumed cochlear origin. Five PFDs were obtained for each group at each of the four test frequencies (500, 2000, 4000, and 8000 Hz). The slopes of PFDs were abnormally steep in some of the hearing-impaired listeners, but were statistically significant only at 2000 Hz. PMID- 2232762 TI - Recognition of voiceless fricatives by normal and hearing-impaired subjects. AB - The purpose of this study was to investigate the sufficient perceptual cues used in the recognition of four voiceless fricative consonants [s, f, theta, integral of] followed by the same vowel [i:] in normal-hearing and hearing-impaired adult listeners. Subjects identified the four CV speech tokens in a closed-set response task across a range of presentation levels. Fricative syllables were either produced by a human speaker in the natural stimulus set, or generated by a computer program in the synthetic stimulus set. By comparing conditions in which the subjects were presented with equivalent degrees of audibility for individual fricatives, it was possible to isolate the factor of lack of audibility from that of loss of suprathreshold discriminability. Results indicate that (a) the friction burst portion may serve as a sufficient cue for correct recognition of voiceless fricatives by normal-hearing subjects, whereas the more intense CV transition portion, though it may not be necessary, can also assist these subjects to distinguish place information, particularly at low presentation levels; (b) hearing-impaired subjects achieved close-to-normal recognition performance when given equivalent degrees of audibility of the frication cue, but they obtained poorer-than-normal performance if only given equivalent degrees of audibility of the transition cue; (c) the difficulty that hearing-impaired subjects have in perceiving fricatives under normal circumstances may be due to two factors: the lack of audibility of the frication cue and the loss of discriminability of the transition cue. PMID- 2232763 TI - The relationship of age and cardiovascular health to certain acoustic characteristics of male voices. AB - The purpose of this investigation was to obtain information about the acoustic characteristics of men's voices as a function of age and cardiovascular health. Eighteen adult males, divided equally into groups of healthy young and elderly men and elderly men diagnosed with chronic atherosclerosis in the absence of other systemic complaints, prolonged the vowel /a/ at a comfortable pitch maintained within 70-78 dB SPL. Measures of mean fundamental frequency (F0), mean jitter and shimmer (both absolute and relative), and the standard deviation of F0, SPL, and peak-to-peak vocal amplitude were computed. Significant differences were found between the healthy young and healthy elderly subjects on measures of F0 and amplitude SD, percent jitter, and shimmer. Differences were generally magnified when the younger subjects were compared with the elderly atherosclerotic subjects. Although only percent jitter significantly differentiated between the two geriatric groups, the atherosclerotics' phonations were generally associated with greater short- and long-term variability (as well as intersubject variability) than the healthy elderly men. Unlike the younger subjects, the elderly (especially the elderly atherosclerotic) subjects' perturbation measures fell much closer to the upper limits established in the literature for normal voices, indicating that the elderly speaker may be more prone to vocal disruption in the face of pathology. PMID- 2232764 TI - Speech production time and judgments of disordered nasalization in speakers with cleft palate. AB - The purpose of this study was to investigate the effect of production time on the perception of disordered nasalization in children with cleft palate. The subjects with cleft palate included 5 who produced acceptable speech consistently, 5 who produced disordered nasalization consistently, and 10 who were inconsistent in the production of disordered nasalization. We examined a range of production times similar to those for the production of single-word and connected speech tasks. Ten judges used direct magnitude estimation to rate severity of disordered nasalization. An accelerometric ratio technique was used to estimate the extent and timing of nasal acoustic activity. The results showed that reducing the production time did not change perceptible nasalization. PMID- 2232765 TI - Estimating respiratory volumes from rib cage and abdominal displacements during ventilatory and speech activities. AB - This methodological study examined the predictive strength associated with modeling respiratory volumes from chest-wall movements during selected ventilatory and speech activities. A linearized magnetometry system transduced the anterior-posterior diameters of the rib cage and abdomen, supplying kinematic data that were used to estimate respiratory volumes. Kinematic and airflow measures were acquired during (a) tidal ventilation, (b) vital capacity maneuvers, (c) Rainbow Passage reading at customary loudness, (d) Rainbow Passage reading at twice-customary loudness, (e) extemporaneous speech, and (f) /a/ prolongation. Multiple-regression statistics were applied to the body surface and integrated airflow data to obtain (a) intercepts, (b) volume-motion coefficients for the rib cage and abdomen, and (c) coefficients of determination. Volumes estimated by applying regression-derived intercepts and volume-motion coefficients to the respiratory kinematic data were then compared to integrated airflow signals. Two magnetometer-based, volume-estimation strategies were contrasted for the speech tasks, one based on volume-motion coefficients derived from that particular speech activity and one based on volume-motion coefficients derived from tidal ventilation. Regression-derived intercepts and volume-motion coefficients for the abdomen varied significantly across subjects but not tasks. Volume-motion coefficients for the rib cage varied significantly across both subjects and tasks. Coefficients of determination for the magnetometer-based volume estimates were affected significantly by subjects and tasks but not by volume-estimation strategies. The calibration, use, and potential limitation of respiratory kinematic devices for speech research are discussed. PMID- 2232767 TI - Acoustical durations of speech segments during stuttering adaptation. AB - Acoustical durations of stutter- and disfluency-free speech segments from Readings #1 and #5 in an adaptation series were measured in 4 adapting, 4 nonadapting, and 4 nonstuttering subjects. The segment durations measured were intervocalic interval, stop-gap, voice onset time, and vowel duration. No clear trends in the change of acoustical durations from Reading #1 to Reading #5 distinguished the adapting, nonadapting, or nonstuttering subjects. Moreover, on the basis of speech naturalness judgements, listeners did not differentiate the Reading #1 and #5 phrase segments of subjects with high adaptation versus those with low adaptation scores. From these findings and related literature, adaptation of stuttering, as well as other fluency-inducing conditions, are viewed as circumstances that reduce demands upon central motor-linguistic processes. PMID- 2232766 TI - Acoustic dimensions of hearing-impaired speakers' intelligibility: segmental and suprasegmental characteristics. AB - Regression and principal components analyses were employed to study the relationship between 28 segmental and suprasegmental acoustic parameters of speech production and measures of speech intelligibility for 40 severely to profoundly hearing-impaired persons in an effort to extend the findings of Metz, Samar, Schiavetti, Sitler, and Whitehead (1985). The principal components analysis derived six factors that accounted for 59% of the variance in the original 28 parameters. Consistent with the findings of Metz et al., a subsequent regression analysis using these six factors as predictor variables revealed two factors with strong predictive relationships to speech intelligibility. One factor primarily reflected segmental production processes related to the temporal and spatial differentiation of phonemes, whereas the other primarily reflected suprasegmental production processes associated with contrastive stress. However, the predictive capability of the present factor structure was somewhat reduced relative to the findings of Metz et al. (1985). Data presented indicate that the populations sampled in the two studies may have differed on one or more dimensions of subject characteristics. Considered collectively, the present findings and the findings of Metz et al. support the tractability of employing selected acoustic variables for the estimation of speech intelligibility. PMID- 2232768 TI - Selected acoustic characteristics of voices before intubation and after extubation. AB - Effects of endotracheal intubation on acoustic characteristics of voices were investigated for 8 male and 8 female subjects using a miniature neck accelerometer and computerized analysis methods. Variables extracted from sustained vowels were (1) spectral slopes of the average waveforms, (2) harmonics to-noise ratios (H/N), (3) coefficients of variation for amplitude (CVA), (4) coefficients of variation for fundamental frequency (CVF), (5) amplitude perturbation (shimmer), and (6) fundamental frequency perturbation (jitter). Fundamental frequency (Fo) distributional statistics (mean Fo, Fo standard deviation, and Fo mid-90% range) were also obtained from oral readings. Results for the sustained vowel samples showed that after extubation, (1) spectral slopes were less steep, and (2) both shimmer and jitter were greater than before intubation. Results for the passage reading revealed that the mean Fo was lower and the Fo standard deviation and mid-90% range were smaller after the extubation than before intubation. It was concluded that even short-term endotracheal intubation affects acoustic characteristics of voice and that selected measures of waveform characteristics are sensitive enough to reveal such effects. PMID- 2232769 TI - Performance of cochlear implant patients as a function of time. AB - The speech perception abilities of 15 patients were measured preoperatively using hearing aids and postoperatively using the Nucleus 22-channel cochlear implant over a period of 1, 2, or 3 years. Analysis of mean data revealed that, although the greatest amount of improvement in speech perception scores occurred between the preoperative and 3-month poststimulation evaluation, there was also significant improvement in perception of segmental features and open-set speech recognition over the 3-year time period. When individual patient data were examined, however, it was clear that these improvements were due, in large part, to the performance of a subset of patients who had measurable open-set speech recognition abilities at the time of their 3-month, poststimulation evaluation. Subjects who used the processing scheme that included coding of F1 showed significantly more improvement over time than subjects who used the original F0F2 processing scheme exclusively. It was concluded that open-set speech recognition ability at 3 months is an important prognostic indicator of continued improvement in speech perception abilities over time. PMID- 2232770 TI - Preferred insertion gain of hearing aids in listening and reading-aloud situations. AB - Nine hearing-impaired subjects with primarily high-frequency hearing loss (Group A) and 8 hearing-impaired subjects with hearing loss in both the high- and low frequency regions (Group B) participated in the experiment. Subjects wore binaural programmable multimemory hearing aids and selected the preferred amount of insertion gain while they listened to discourse passages read by a male speaker (listen). Subjects also selected the preferred amount of gain while they listened to themselves as they were reading the same passages (read-aloud). Subjects' word-recognition performances and their subjective impressions of the hearing aids determined in listen and read-aloud conditions were examined on subsequent listening and reading tasks. Hearing-impaired subjects preferred more insertion gain in the listen condition than in the read-aloud condition. Different insertion gains led to different objective and subjective performances. Hearing-aid responses selected for a particular condition (listening vs. reading aloud) yielded the best performance in that condition. Assuming the primary purpose of a hearing aid is for amplifying the speech of others, these findings suggest that one should not adjust the gain of a hearing aid using one's own voice as the reference. In addition, one should be careful in soliciting subjective comments from hearing-impaired patients during hearing-aid fittings to avoid underamplifying those individuals in the low frequencies. Multimemory hearing aids may be necessary for some hearing-impaired patients to use their hearing aids satisfactorily in listening and speaking conditions. PMID- 2232771 TI - Simple triangular approximations of auditory filter shapes. AB - At present, the most popular auditory filter shape model is one with a rounded peak and exponentially decaying filter skirts (Patterson & Moore, 1986). Unfortunately, the complex nature of this "roex" filter model may, in some instances, have hindered the application of the auditory filter shape in clinical measurements of frequency selectivity. Moreover, some of the assumptions of the roex filter model may be violated at high sound-pressure levels (SPLs) and this limitation has also been a factor when considering the roex auditory filter shape in the clinic. Our purpose is to introduce a simplified method that is adequate for obtaining clinically useful estimates of triangular-shaped auditory filters. Although the triangular-shaped filter model faces the same problems as the roex model at high SPLs, the calculations and assumptions underlying the former are far less complicated. The triangular filter model also retains many of the qualitative properties and advantages afforded by roex-fitted auditory filter shapes. In this report, we review the basic concepts underlying auditory filter shape estimates and describe our methods for measuring and fitting the triangular shaped filter model. We then present normative triangular filter shapes and compare these estimates with auditory filter shapes fitted by other means. Finally, we present selected examples of triangular filter shapes fitted to the masked thresholds of hearing-impaired patients. For the most part, the triangular shaped filter model offers the clinician a satisfactory compromise for obtaining estimates of auditory filter shape and frequency selectivity at moderately intense and high SPLs. PMID- 2232772 TI - Differential learning of phonological oppositions. AB - This study evaluated whether variations in the structure of minimal versus maximal opposition treatments would result in empirical differences in phonological learning. Subjects were 3 children who excluded at least six sounds from their pretreatment phonetic and phonemic inventories. An alternating treatments design in combination with a staggered multiple baseline across subjects was used to evaluate differences in learning the two types of oppositions. Results indicated that treatment of maximal oppositions led to greater improvement in the children's production of treated sounds, more additions of untreated sounds to the posttreatment inventory, and fewer changes in known sounds than treatment of minimal oppositions. Moreover, individual differences suggested that phonological learning was enhanced not only by the number but also by the type of distinctions being taught. A potential sequence of relative clinical effectiveness was proposed such that teaching multiple and major class distinctions greater than teaching multiple distinctions greater than teaching few distinctions among sounds. PMID- 2232773 TI - Rotation and translation of the jaw during speech. AB - A two-dimensional rigid-body model of jaw movement was used to describe jaw opening and closing gestures for vowels and for bilabial and alveolar consonants. Jaw movements were decomposed into three components: (a) rotation about the terminal hinge axis, (b) the horizontal translation of that axis, and (c) the vertical translation of that axis. Data were collected for 3 subjects in two separate recording sessions. Multiple regression analysis was used to examine the relationships among the three jaw movement components. For 2 subjects, but not for the third, an interdependence between jaw rotation and the first principal component of jaw translation, horizontal translation, was observed. For these 2 subjects, the first degree of freedom of jaw movement corresponded to a combination of rotation and the first principal component of jaw translation. For the third subject, the first degree of freedom of jaw movement corresponded to rotation alone. The results of this study, like those of Westbury (1988), indicate that an accurate description of jaw movement during speech requires the recording of two points of jaw movement. PMID- 2232774 TI - Semantic memory deterioration in Alzheimer's subjects: evidence from word association, definition, and associate ranking tasks. AB - The nature of semantic memory impairment in 23 persons with dementia of the Alzheimer type (DAT) was studied using three semantic tasks: word association, definition, and associate rank ordering. Using hierarchical log-linear analysis of the responses to the word association task, DAT subjects were more likely than normal control subjects to give multiword, repetitious, or unrelated responses. Additionally, the ratio of paradigmatic to syntagmatic responses was significantly decreased in DAT subjects. Surprisingly, DAT subjects were able to provide definitions for many stimulus words for which they were unable to provide meaningful associates. This finding suggests the need for caution in interpreting a decrease in the number of paradigmatic responses as indicative of a loss of conceptual knowledge. Results of other analyses demonstrated that DAT subjects had significant impairment in identifying highly related and unrelated semantic associates of words. Taken together, results of this study indicate that one feature of DAT is deterioration in the associative relations between concepts. PMID- 2232775 TI - Syllable durations of preword and early word vocalizations. AB - The continuity in development of syllable duration patterns was examined in 7 young children as they progressed from preword to multiword periods of vocalization development. Using a combination of lexical and chronological age points, monthly vocalization samples were analyzed for bisyllable duration and final syllable lengthening. Results revealed no systematic increase or decrease in the duration of bisyllables produced by the children as a group. Lengthening of final syllables was observed across nearly all recording sessions for all children. It is likely that the feature of bisyllable duration is not discernibly sensitive to changes associated with a developing speech mechanism and environmental input. On the other hand, the regularity in final syllable lengthening is consistent with a continuity theory of development. PMID- 2232776 TI - Distortion-product otoacoustic emissions in humans with high frequency sensorineural hearing loss. AB - Distortion-product otoacoustic emissions (DPOAEs) and pure-tone behavioral thresholds were compared in 20 ears with normal hearing and in 20 ears with high frequency sensorineural hearing loss. The purpose was to determine if DPOAE amplitude is associated with pure-tone behavioral threshold. Comparison of results from the two groups of ears indicated that DPOAEs were reduced in amplitude or were absent in ears with high-frequency hearing loss. The differences occurred at frequencies above 1,500 Hz. Comparing results from 750 to 8,000 Hz within the same ear revealed a frequency-related correspondence of elevated behavioral threshold to reduced DPOAE amplitude. When behavioral thresholds were better than 20 dB HL, DPOAE amplitude was within the range (+/- 2 SDs) determined for the ears with normal hearing. When pure-tone threshold was greater than 50 dB HL, DPOAEs were absent or were significantly attenuated in 16/17 subjects (94%). The association of emission level with behavioral threshold level was variable when threshold was between these two extremes. Results imply that the measurement of DPOAEs has clinical potential as a means of detecting hearing loss by frequency. PMID- 2232777 TI - Glottal closure and perceived breathiness during phonation in normally speaking subjects. AB - Glottal closure and perceived breathiness were evaluated in 9 female and 9 male normally speaking subjects ranging in age from 20 to 35 years. Phonations of the vowel /i/ at three loudness and pitch levels were performed. The degree of glottal closure was judged by speech clinicians from video-fiberstroboscopic recordings. Later they rated the degree of perceived breathiness both in the vowels recorded during the fiberscopy and in separately tape-recorded vowels. Intra- and interjudge reliabilities were satisfactory. The degree of incomplete glottal closure and the degree of perceived breathiness increased significantly as an effect of decreased loudness. Neither the degree of closure nor the perceived breathiness were significantly affected by changes in pitch or by interaction effects. It was concluded that incomplete glottal closure of the posterior parts of glottis should be regarded as normal primarily in women and that loudness should be taken into consideration when studying glottal closure and breathiness. PMID- 2232778 TI - Critical differences in aided sound field thresholds in children. AB - Variability of aided sound field thresholds (ASFTs) was examined in 30 children comprising two age groups (5-9 and 10-14 years). Test-retest ASFTs were collected at six frequencies (250, 500, 1000, 2000, 3000, and 4000 Hz). No statistically significant difference was found in mean test and retest ASFTs between the two groups (p greater than .05). Test-retest difference data from both groups of children were combined and used to generate critical differences (in dB) for two ASFTs. At a 95% confidence level, two ASFTs would have to differ by more than 10 dB across signal test frequencies to attain statistical significance. In clinical decision-making, if one accepts smaller differences in ASFTs as statistically significant, larger probabilities of error must be assumed. PMID- 2232779 TI - Fine-grained discrimination deficits in language-learning impaired children are specific neither to the auditory modality nor to speech perception. PMID- 2232780 TI - Vocal fundamental frequency variability in young children: comments on Robb and Saxman (1985) PMID- 2232781 TI - Vasa previa. AB - Diagnosis of vasa previa requires a high index of suspicion. Vasa previa must be included in the differential diagnosis of all cases of third trimester bleeding. When pulsatile vessels are palpated preceding the fetal vertex, vasa previa should be considered along with cord prolapse. Early diagnosis and intervention result in a favorable fetal outcome in this rare condition. PMID- 2232782 TI - More than 17,000 transurethral prostatic resections (TURs): some of the things I have learned. PMID- 2232783 TI - Traumatic lung cyst. PMID- 2232784 TI - An unusual case of ventricular tachycardia. PMID- 2232785 TI - A case of refractory hypotension. PMID- 2232786 TI - Communicable disease reporting: why? PMID- 2232788 TI - Rockin' the boat: a footnote on history. PMID- 2232787 TI - Durable powers of attorney for health care decisions: understanding the latest malpractice risk. PMID- 2232789 TI - Compared to what? PMID- 2232790 TI - Alcohol consumption by college undergraduates: current use and 10-year trends. AB - In a carefully executed study with a high response rate, a random sample of 10% of the undergraduate student body at a rural New England university was surveyed as to the subjects' use of alcohol in 1987. Over 87% of the surveyed students returned questionnaires. The results were compared to similar studies conducted on the campus in 1977 and 1983. "Daily or almost daily" use of alcohol was registered by 4.7% of the respondents, which represents a continuing decrease in daily consumption from earlier studies. One-fourth of the sample indicated drinking only one drink or fewer per week, contrary to the common perception on the campus. Nevertheless, 25.5% recorded a hangover, 7.5% recorded vomiting from drinking too much and 4.4% recorded a blackout, all "in the last week." Compared to the U.S. population, alcohol consumption appears to be more evenly distributed in the college sample but, still, most of the drinking is done by one-fifth of both groups. PMID- 2232791 TI - Alcohol consumption and problem drinking in Vietnam era veterans and nonveterans. AB - The relationship between Vietnam era veteran status and 13 indicators of alcohol consumption and problem drinking is examined using data from the 1977, 1983 and 1985 National Health Interview Surveys conducted by the National Center for Health Statistics. Compared to a group of nonveterans frequency matched on age, a greater proportion of Vietnam era veterans are currently heavy drinkers and a smaller proportion are abstainers, after simultaneous adjustment for seven demographic factors (age, region of the U.S., urbanization, ethnicity, marital status, education and income). Further, both white veterans and white nonveterans demonstrate an effect of increasing abstention with increasing age across the 3 interview years. In all race and veteran groups the proportion of lifetime abstainers can be ranked in increasing order as follows: white veterans, white nonveterans, non-white veterans and non-white nonveterans. This ranking is reversed for lifetime heavy drinking. Nearly half of the white veterans report drinking heavily at some point in their lives. Among both whites and non-whites, a significantly greater proportion of veterans than nonveterans report alcohol related motor vehicle crashes or violations. PMID- 2232793 TI - Agreement between two dietary methods in the measurement of alcohol consumption. AB - This study compares estimates of alcohol consumption from two dietary methods: a self-reported diet diary and a quantitative food frequency questionnaire. In the 1984-85 University of Michigan Food Frequency Study, 228 black and white, male and female respondents, ages 23-51 years, kept diet diaries covering 16 days during a 1-year period. At the end of the year, the same respondents completed a dietary quantity-frequency questionnaire that included alcoholic beverages. The two methods showed excellent agreement in estimated group mean ethanol consumption and good agreement in the ranking of individual respondents. Respondents described alcohol consumption in abstract terms on the questionnaire in a way that was consistent with the consumption recorded in the diary. However, the two methods showed only poor to moderate agreement in classifying individuals as infrequent, moderate or heavier drinkers, suggesting that such classifications should be used cautiously. These results suggest that in general population studies a dietary quantity-frequency questionnaire and a diet diary covering several weeks can measure moderate levels of alcohol consumption similarly. The degree of consistency suggests that, for moderate levels of intake, measures of alcohol consumption derived from the two methods are equally valid. PMID- 2232792 TI - Recall of alcohol consumption during pregnancy. AB - This is a test-retest reliability study of self-reported alcohol use during pregnancy, in which two groups of women provided two reports about their first trimester drinking over a 3-month interval (Group 1) and over a 5-month interval (Group 2). Women in Group 1 (n = 91) were queried about first trimester alcohol consumption during their fourth month of pregnancy and again during their seventh month, a 3-month recall interval. Group 2 women (n = 88) provided first trimester drinking reports during their fourth month of pregnancy and again at delivery, a 5-month recall interval. The test-retest Pearson correlation coefficient for recall of first trimester average daily volume (ADV) was .61 (p = .000) for Group 1 and .53 (p = .000) for Group 2. When the ADV scores were grouped into five ordinal categories, 51.6% of Group 1 and 56.8% of Group 2 remained in the same category at test and retest. This leads to the conclusion that self-reported alcohol consumption is moderately reliable over a 3-month and a 5-month time period. PMID- 2232794 TI - Anomie, alcohol abuse and alcohol consumption: a prospective-analysis. AB - Cross-sectional and 36-month prospective analyses of the relationships among anomie and both alcohol abuse and alcohol consumption patterns provided little support that anomie was directly associated with ethanol ingestion patterns in a sample of 302 male air traffic controllers. This lack of association was observed for self-reported alcohol consumption, interview-established alcohol abuse and biochemical markers of alcohol intake. In addition, anomie was not predictive of change in alcohol use/abuse over 36 months, controlling for baseline levels of alcohol use and abuse and for relevant demographic factors. Measurement of anomie and alcohol use/abuse, the relative importance of anomie in various socioeconomic groups and issues related to prospective research on this topic are discussed. PMID- 2232795 TI - The situational riskiness of alcoholic beverages. AB - Using face-to-face interview data on a sample of young adults, this study investigates the perceived risk of alcohol consumption in drinking and driving, interactions with police and the probability of intoxication. Results show that beer is perceived as less risky than liquor in two risk situations, with men and drinkers in particular ranking beer as a lower risk beverage. When intoxication is considered, drinkers rank their preferred beverage as less risky than their alternative. Finally, an analysis of the relative riskiness of beer in comparison to liquor reveals that beer is perceived as less risky than liquor. This consensus does not vary significantly by sex or most other respondent characteristics. PMID- 2232796 TI - Portrayals of alcohol on prime-time television. AB - Alcohol portrayals were analyzed for a 3-week composite sample of prime-time fictional television programs aired in the fall of 1986. Approximately 64% of the 195 episodes contained one or more appearances of alcohol. Alcohol was ingested on 50% of all programs. Overall, there were 8.1 alcohol drinking acts per hour. Movies made-for-television had the highest rate of drinking acts per hour (10.0) followed by situation comedies (9.2) and then theatrical movies (7.4) and dramas (7.4). Within the category of dramas, evening soap operas stand out with 13.3 acts per hour. Drinking and nondrinking characters were compared on a number of attributes relevant to role modeling. Regularly appearing characters were more likely to drink than nonregular characters. Drinking characters also tended to be of high status, largely being white, upper-class professionals. A time trend analysis showed a regular increase in alcohol on television from 1976 to 1984, reaching 10.2 acts in 1984. After 1984 the trend appears to reverse. PMID- 2232797 TI - Public support for policy initiatives regulating alcohol use in Minnesota: a multi-community survey. AB - Public support for policies to control alcohol sales and consumption was surveyed in seven Minnesota communities. A total of 438 women and 383 men were asked to indicate their level of support of or opposition to nine different proposals designed to regulate alcohol. There was general support for all policies, which was strongly related to characteristics of respondents and type of policy proposed. Women were significantly more supportive of all items than were men. Marriage, older age and low alcohol consumption were also associated with support. Education and voter status generally were not. Policies and activities that serve primarily to protect youth received the strongest support. Restrictions and prohibitions such as limiting advertisements were less popular. The least support was expressed for increases in taxes on alcohol and for measures that would eliminate an existing practice such as prohibiting wine cooler sales at convenience stores. The majority of respondents also indicated that they felt the individual, as opposed to the manufacturer or retailer, was responsible for problems associated with alcohol and should be the focus of intervention. Strategies for shifting the focus from the individual to environmental and regulatory control are discussed. PMID- 2232799 TI - The relationship between ethanol intake and DSM-III-R alcohol dependence. AB - The purpose of this investigation was to quantify the relationship between ethanol consumption and DSM-III-R alcohol dependence using mathematical modeling techniques that allowed for the control of confounding and assessment of interaction. Although sex, education, ethnicity and marital status were not identified as actual confounders in the logistic regression model, the ethanol intake-dependence association was stronger among younger as opposed to older respondents. For 20 year olds, the average log odds for dependence increased .62 for each additional ounce of ethanol consumed daily, while the corresponding increase in risk among 60 year olds was .26. Implications of these results are discussed in terms of age differences in drinking patterns and differential social control of drinking behavior. Separate analyses in which aggregates of the alcohol dependence criteria served as outcome measures helped qualify the interpretation of the overall ethanol intake-dependence relationship. The need to examine components of global classifications of alcohol dependence using better operationalizations is highlighted. PMID- 2232798 TI - A comparison of familial and nonfamilial male alcoholic patients without a coexisting psychiatric disorder. AB - Both family history of alcoholism and the presence of additional psychiatric disorder in male alcoholic patients are associated with an earlier onset of problem drinking, greater alcoholism severity and poorer clinical outcomes. To assess the relative contribution of family history alone, a sample of 212 male alcoholics not positive for any other psychiatric disorder was selected and divided into those with a family history of alcoholism (FH+) or no family history of alcoholism (FH-) among first degree relatives. Although FH+ alcoholics reported a younger age of onset of problem drinking and greater severity of some alcohol-related sequelae, the differences were not as extensive or pronounced as those found in a previous study of a sample of psychiatrically heterogeneous patients (Penick et al., 1987). A bi-dimensional typology of alcoholism incorporating both additional psychiatric diagnoses and a positive family history of alcoholism is suggested. PMID- 2232800 TI - The MAC scale in a normal population: the meaning of "false positives". AB - The MAC scale has been very successful in identifying alcoholics and, in studies of clinical populations, is often considered a test for predisposition to alcoholism. MacAndrew, however, holds that the MAC scale assesses a more general personality trait characterized by sociability, boldness, rebelliousness and pleasure seeking. The present study examines the distribution of MAC scale scores in a normal population and tests for correlates of high MAC scores other than alcohol-related problems (e.g., arrest history). The sample consisted of 1,117 men, participants in the Normative Aging Study (mean age = 61.6). As expected, heavier drinkers and problem drinkers reported significantly higher MAC scale scores than did lighter and nonproblem drinkers. However, arrestees without drinking problems had MAC scale scores nearly identical to those of problem drinkers without arrest histories (23.19 and 23.42, respectively). Further, 36% of the sample without problem drinking or arrest histories had MAC scale scores of 24 or above, the clinical indicator of alcoholism, and more than 32% of these had scores above 27. In the entire sample, of the 152 men who had MAC scores above 27, 71% had no problems, either with arrest or drinking. Results are interpreted as supporting MacAndrew's interpretation of the meaning of the MAC scale as a general personality measure rather than a specific alcoholism instrument. PMID- 2232801 TI - The effect of gender and subtype on platelet MAO in alcoholism. AB - Decreased platelet MAO activity has been identified in male alcoholics with suggestions that this is primarily true of Type 2 alcoholics as defined by criteria from the Stockholm Adoption Study. Little information has been available regarding platelet MAO activity in female alcoholics. This study evaluated a group of 71 alcoholics receiving inpatient treatment, including 16 female alcoholics, for platelet MAO activity compared to controls. Female alcoholic's platelet MAO was significantly lower than controls and not different from activity levels in male alcoholics. Among male alcoholics, both Type 1 and Type 2 subgroups were lower than controls and Type 2 levels did not differ from Type 1 levels. Thus, we were unable to replicate a gender and subgroup low platelet MAO specificity among alcoholics, but did find significant differences between alcoholics and controls. PMID- 2232802 TI - The acute effects of alcohol on the blood pressure of young, normotensive men. AB - Alcohol's acute effects on arterial blood pressure (BP) were examined. To separate the effects of alcohol on BP from those of fluid volume and expectancy, normotensive men were divided into three groups. The alcohol group received 1.0 ml of absolute alcohol/kg of body weight. The expectancy group expected alcohol but received only tonic. The control group expected and received only tonic. With age as a covariate, significant changes in systolic BP were found only in the alcohol group, indicating that the changes in systolic BP were not attributable to subject expectancy or volume of fluid consumed. The expectancy control groups did not differ from each other. A significant quadratic trend was found for systolic BP in the alcohol group, suggesting that alcohol may have an acute biphasic effect on systolic BP, with an initial decrease as the alcohol is ingested followed by an increase toward the basal level during detoxication. No significant effects were found for diastolic BP. PMID- 2232803 TI - Preoperative cell-mediated immune function and the prognosis of patients with gastric carcinoma. AB - The cell-mediated immune function of 83 patients with gastric carcinoma was assessed preoperatively and the results were compared to that of 52 patients with benign lesions. The data were subjected to an analysis in order to evaluate their prognostic significance. The abilities to induce allogeneic cytotoxicity and to produce interleukin 2 (IL2) in patients with stage IV carcinoma were significantly depressed, as compared to those in patients with benign lesions, whereas natural killer (NK) cell activity was not significantly impaired. There was no significant correlation among these immune functions. When the patients were stratified into two groups, those who had high (greater than the mean value in patients with benign lesions) and low (less than the same value) values of these immune reactivities, the survival of patients with high NK activity (greater than or equal to 43%) was significantly better, as compared to that of patients with low cytotoxicity (less than 43%). However, there was no correlation between the survival and allogeneic cytotoxicity in these patients. The high ability to produce IL2 (greater than or equal to 1.3 U/ml) correlated with the better survival in the patients, but not in the group of patients who underwent curative resection. PMID- 2232804 TI - Toxicity comparison of neoadjuvant versus adjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) in radical cystectomy patients. AB - A reduction in the toxicity of M-VAC chemotherapy has been postulated for patients who receive these drugs prior to radical cystectomy for muscle invasive bladder carcinoma. A review of the toxicity and patient dropout rates from a group of 9 patients who received neoadjuvant M-VAC was little different from 9 patients who were treated with M-VAC after radical cystectomy. This similarity suggests that preoperative M-VAC should not be favored on the basis of reduced patient morbidity. PMID- 2232805 TI - Adenocarcinoma arising in Barrett's esophagus. AB - A review of nine adenocarcinomas of the esophagus arising in Barrett's epithelium was undertaken. We found the disease among white males disproportionately. Risk factors and incidence rate remain to be clarified. Only one patient was in a surveillance program and only he had carcinoma discovered "early." He still survives while only one of the eight whose diagnosis followed investigation of symptoms remains alive. PMID- 2232807 TI - Obstructing carcinoma of the cecum. AB - Carcinoma of the cecum, the third most common location for malignancy of the large bowel, was examined with attention centered upon cecal cancers producing obstruction. Reviewing 136 patients revealed 11 obstructing lesions (8.1%) presenting as distal small bowel obstructions. The mean age of the patients was 74 years. All but one patient had resection for cure which consisted of a right hemicolectomy with ileotransverse colostomy. There was no operative mortality or significant morbidity. Bowel obstruction due to cecal carcinoma is an infrequent occurrence arising in elderly patients and carries a poor survival rate due to advanced disease at the time of diagnosis and treatment. PMID- 2232806 TI - Neoadjuvant Cis-DDP in esophageal cancers: an experience at a regional cancer centre, India. AB - We are analysing the results of 80 patients who underwent surgery during 1983-84 for esophageal cancer. Forty patients who received pre-operative single agent Cis DDP were grouped under "A" and 40 patients who went for surgery directly were grouped under "B". Twenty-two patients (55%) of Group A showed tumor necrosis. Both groups underwent resection and hand-sewn anastamosis of the esophagus. There were 10 post-operative deaths among 80 resected cases, 9 of them being from anastomatic leak. Cis-DDP has induced negligible side effects. A comparatively high survival rate during early years in patients who responded to Cis-DDP suggests that neoadjuvant chemotherapy might be of value. PMID- 2232809 TI - Carcinoma of the pancreas: a retrospective review. AB - Eighty-five patients with adenocarcinoma of the pancreas were reviewed in order to evaluate the efficacy of our methods of diagnosis and treatment. The most useful diagnostic test was percutaneous transhepatic cholangiography (PTC) with a diagnostic rate of 96%. Pancreaticoduodenectomy (Whipple procedure) and total pancreatic resection were performed in 13 and 2 patients, respectively. The remaining 50 patients underwent various palliative drainage procedures. Twenty patients did not undergo operation for various reasons. The primary tumor was found in the head of the pancreas in 50 patients (59%), the body in 6 patients (7%), and in the tail in 8 patients (9%). Postoperative complications, including sepsis, bleeding, intra-abdominal abscesses, and anastomotic leaks, occurred in 37% of the patients. There were one operative and 9 postoperative deaths. The average survival for those patients undergoing surgical intervention was 6 months. There were no 5-year survivors. PMID- 2232810 TI - In vivo selection and characterization of a murine mammary tumor subline with high potential for spontaneous lymph node metastasis. AB - A transplantable mammary adenocarcinoma, grown in Balb/c mice, with a marked enhancement in its draining lymph node metastatic ability (MM3LN), was obtained through an in vivo procedure from a variant tumor moderately metastatic to lymph nodes (MM3). Both MM3 and MM3LN presented a similar latency and tumor growth rate and reached the same tumor mean diameter at death. MM3LN tumor-bearing mice exhibited a larger mean survival time. The new variant showed a 2.5-fold higher incidence of tumor-draining lymph node metastases than MM3 line, with no differences in the incidence of lung metastases. Morphology as well as cytogenetic and in vitro adhesion properties were studied in order to characterize the new subline. This murine tumor model has potential application in the study of the metastatic process in lymphoid tissue. PMID- 2232808 TI - Complications of stapled anastomoses in anterior resection for rectal carcinoma: colorectal anastomosis versus coloanal anastomosis. AB - Postoperative results of 48 patients who underwent anterior resection using the EEA-stapler were evaluated. In all but 2 cases the indication for surgery was colorectal carcinoma. In 24 patients an anastomosis was created above the 5 cm level (above the anal verge: colorectal anastomosis) and in 24 at the 0-5 cm level (coloanal anastomosis). There was no perioperative mortality. The only complication observed in the colorectal anastomosis group was one case of late anastomotic stenosis. In the coloanal anastomosis group there were 4 cases with early anastomosis leaks, 3 cases with late stenosis and 5 cases with various degrees of late fecal incontinence, ultimately resulting in a permanent diverting stoma in 5 (10.4%) patients. We conclude that for rectal tumors the EEA-stapled anterior resection provides excellent functional results in most cases. Stapled coloanal anastomoses more often demonstrate various (early and late) complications. Nevertheless in spite of chronic discomfort, many patients still prefer their complaints to a permanent stoma. PMID- 2232812 TI - Ampullary carcinoma in patients under 50 years of age with a poor prognosis. AB - Clinicopathologic features of 145 Japanese patients with ampullary carcinoma were compared among three age groups. The 145 patients were divided into three groups by the patient's age at the time of operation; there were 24 patients in group I (younger) aged less than or equal to 50 years, 99 in group II (ordinary) aged 51 69, and 22 in group III (elderly) aged greater than or equal to 70. The three groups showed no significant difference in sex, icterus, duration of icterus, size of the tumor, year of operation, macroscopic type, histopathologic type, tumor margin, lymphatic permeation, venous invasion, or pancreatic invasion. The survival curve of group I was worse than those of groups II and III. Multivariate regression analysis using 11 prognostic variables failed to reveal that the age of the patient at the time of operation was an independent factor. The younger patients aged less than or equal to 50 fared worse than the elderly patients aged greater than or equal to 70, because the group I tumors included a significantly greater number of advanced ampullary carcinoma with more frequent perineural invasion than did the group III tumors. PMID- 2232811 TI - Rat liver tolerance for partial resection and intraoperative radiation therapy: regeneration is radiation dose dependent. AB - We studied the feasibility of delivering a large single dose of intraoperative radiation as an adjuvant to partial hepatic resection. Intraoperative radiation therapy (IORT) was delivered to the remaining liver of 84 rats after partial hepatectomy to determine the acute and chronic effects of treatment on blood chemistry values, histology, survival, hepatic regeneration, and cellular appearance of the normal liver. Transient elevations in SGOT, SGPT, and alkaline phosphatase were attributed both to hepatectomy and to liver parenchymal damage induced by IORT. Microscopic examination upon necropsy, performed at frequent intervals post-treatment revealed hepatic capsular thickening with some alteration of liver architecture mainly underneath the capsule, with localized inflammation and some areas of necrosis. Survival in all groups was 100% at 45 days. Liver weight increase proved to be dose-dependent and displayed a bisphasic pattern. This study demonstrated that IORT is a feasible adjunct to surgical resection of the liver in the rat model. PMID- 2232813 TI - Colon carcinoma associated with ureterosigmoidostomy. AB - A patient developing a colonic adenoma 38 years following ureterosigmoidostomy is presented. The mechanisms of neoplastic transformation associated with ureterosigmoidostomy is now better understood. This knowledge is being applied to develop modifications both of the surgical technique and the management of patients with this form of urinary diversion, and is a subject of discussion. PMID- 2232814 TI - Metastatic tumors of the umbilicus: a review 1830-1989. AB - Umbilical metastases from known and unknown primary cancers are rare. The eponym "Sister Mary Joseph's nodule" has been used by generations of physicians. The first reports of this clinical sign were from Walshe in 1846. A review of the literature revealed 265 cases from then until 1989. Only 85 cases of umbilical metastasis from unknown primary tumors were found. This review should help us to focus on the common and uncommon primary sites in the diagnosis of patients with this finding. A single case report and the work-up for the hidden primary tumor are described. PMID- 2232815 TI - Simple and effective procedure for complete urine collection from infant macaques (Macaca nemestrina). AB - A diaper method, used in pediatric medicine, has been adapted and validated for total urine collection from infant macaques (Macaca nemestrina). The device consists of cellulose sponges and polyethylene sheets. The method proposed is non invasive, simple, and does not significantly hinder the movement of the infant. The method should be useful when one is conducting pharmacokinetic studies in which total urine collection is required. PMID- 2232816 TI - Methamphetamine- and apomorphine-induced changes in spontaneous motor activity using a new system to detect and analyze motor activity in mice. AB - A new system was devised to detect animal spontaneous motor activity in more detail, and methamphetamine- and apomorphine-induced changes in spontaneous motor activity were analyzed using this system. The system consists of a doughnut shaped cage with 36 units of detectors. Scanning of each detector unit was three dimensionally carried out, and then scanning data were fed into a personal computer. These steps were completed within 0.1 sec and repeated. Spontaneous motor activity was analyzed as changes in parameters, such as total activity, locomotor activity, vertical activity (the number of rearings and the rearing time), motion time, and average speed. Regarding dependence on the dosages of methamphetamine and apomorphine, the time courses of changes in total activity and locomotor activity markedly differed from those for changes in vertical activity. Changes in the numbers of rearings and rearing time induced by 2 mg/kg methamphetamine peaked 40-80 min after administration, whereas those in other parameters did so 15-25 min after. Three mg/kg apomorphine-induced changes in total activity and locomotor activity showed two peaks 10-15 and 40-50 min after administration, respectively. At the same dosage, apomorphine markedly increased rearing time with slight but not significant effects on the number of rearings. These effects peaked 20-30 min after administration. These results indicate this system to be quite useful to detect and analyze drug-induced changes in spontaneous motor activity. PMID- 2232817 TI - Extraction of physostigmine from biologic fluids and analysis by liquid chromatography with electrochemical detection. AB - A rapid and simple method is described for the extraction of physostigmine (Phy) and its hydrolysis product, eseroline, from plasma, whole blood, and cerebrospinal fluid (CSF) and their subsequent quantitation by high-performance liquid chromatography (HPLC) with dual electrode electrochemical detection. Phy and eseroline were extracted from biologic fluids with cyano-phase columns eluted with 0.1 M citrate buffer, pH 4 containing 20% acetonitrile. Phy recovery from citrate buffer and CSF was nearly 100%. Phy recovery from plasma was 82% when methanol was used to precipitate proteins and 62% when HClO4 was used to precipitate proteins. Phy recovery from whole blood was only 17%. These results are discussed in the context of attempting to measure Phy in fluids of patients receiving this drug in clinical trials for the treatment of Alzheimer's disease. PMID- 2232818 TI - Transitory models of experimentally induced intraocular pressure changes in the rabbit. A reappraisal. AB - The purpose of this study was to evaluate the relationship between inducer dosage, animal weight, and kinetics intraocular pressure (IOP) changes in three transitory-induced models for antiglaucoma drugs screening: oral water-loading, 5% glucose intravenous administration, and 20% NaCl infusion. For these models, a dose-dependent elevation of IOP was observed in three weight groups of rabbits (1, 2.2, and 3.8 kg). Dose-effect relationships were established, considering for each weight group two relevant parameters: maximal IOP changes and areas under or upper the kinetic curves of IOP changes. Among the three models studied, our results led us to consider water-loading as a weight-independent model, allowing us to compare results obtained by this model in New Zealand rabbits with different ages (40-150 days) or weights (0.9-3.8 kg). PMID- 2232820 TI - Strong stability and density-dependent evolutionarily stable strategies. AB - Stability conditions for equilibria of the evolution of population strategies in a single species are developed by comparing frequency and density dependent fitnesses of pairs of strategies. Stability of such equilibria is shown for general haploid frequency and density dynamics. It is also shown that this stability is stronger than that of multispecies population dynamical systems. A biological interpretation of the conditions is provided in terms of the fitness of invading subpopulations. PMID- 2232821 TI - Group selection among alternative evolutionarily stable strategies. AB - Many important models of the evolution of social behavior have more than one evolutionarily stable strategy (ESS). Examples include co-ordination games, contests, mutualism, reciprocity, and sexual selection. Here we show that when there are multiple evolutionarily stable strategies, selection among groups can cause the spread of the strategy that has the lowest extinction rate or highest probability of contributing to the colonization of empty habitats, and that this may occur even when groups are usually very large, migration rates are substantial, and "extinction" entails only the disruption of the group and the dispersal of its members. The main requirements are: (1) individuals drawn from a single surviving group make up a sufficiently large fraction newly formed groups, and (2) the processes increasing the frequency of successful strategies within groups are strong compared to rate of migration among groups. The latter condition suggests that this form of group selection will be particularly important when behavioral variation is culturally acquired. PMID- 2232819 TI - Isolated perfused rat kidney as a tool in the investigation of renal handling and effects of nonsteroidal antiinflammatory drugs. AB - An isolated perfused rat kidney (IPK) preparation is described in which renal perfusion flow, perfusion pressure, urinary flow, urinary pH, and glomerular filtration rate (GFR) are recorded continuously during the perfusion experiment. The usefulness of this IPK system in studying the renal handling and the effects of non-steroidal antiinflammatory drugs (NSAIDs) is shown using salicyluric acid (SU), salicylic acid (SA), and naproxen (NA). Excretion of SU involves glomerular filtration, active secretion, and passive reabsorption. The excretion rates of SA and NA were both much lower than their filtration rate, indicating extensive reabsorption. All three drugs accumulate in the IPK but at different levels. SU accumulates much more than either SA or NA. The effects on renal function were different for the three drugs studied. SU had no effect on kidney function. SA perfusate concentrations greater than 100 micrograms/mL caused diuresis and natriuresis, while SA concentrations less than 100 micrograms/mL did not influence kidney function. NA perfusate concentrations ranging from 0.16 to 25 micrograms/mL caused a decrease in urinary flow and sodium excretion. Very high NA concentrations (greater than 500 micrograms/mL) caused an increase in urinary flow and sodium excretion. We conclude that the IPK is a suitable preparation for characterizing and comparing renal handling and effects of NSAIDs. PMID- 2232822 TI - Drosophila segmentation: supercomputer simulation of prepattern hierarchy. AB - Spontaneous prepattern formation in a two level hierarchy of reaction-diffusion systems is simulated in three space co-ordinates and time, mimicking gap gene and primary pair-rule gene expression. The model rests on the idea of Turing systems of the second kind, in which one prepattern generates position dependent rate constants for a subsequent reaction-diffusion system. Maternal genes are assumed responsible for setting up gradients from the anterior and posterior ends, one of which is needed to stabilize a double period prepattern suggested to underly the read out of the gap genes. The resulting double period pattern in turn stabilizes the next prepattern in the hierarchy, which has a short wavelength with many characteristics of the stripes seen in actual primary pair-rule gene expression. Without such hierarchical stabilization, reaction-diffusion mechanisms yield highly patchy short wave length patterns, and thus unreliable stripes. The model yields seven stable stripes located in the middle of the embryo, with the potential for additional expression near the poles, as observed experimentally. The model does not rely on specific chemical reaction kinetics, rather the effect is general to many such kinetic schemes. This makes it robust to parameter changes, and it has good potential for adapting to size and shape changes as well. The study thus suggests that the crucial organizing principle in early Drosophila embryogenesis is based on global field mechanisms, not on particular local interactions. PMID- 2232823 TI - Frequency specific modulation of bone adaptation by induced electric fields. AB - A frequency specificity for the response of bone tissue to a physical stimulus is proposed. This is obtained by comparing the spectral power of exogenously induced electric fields to the efficacy of those fields to inhibit immobilization induced bone loss in an in vivo model of skeletal adaptation. Analysis of a family of related waveforms shows that the effectiveness of the induced electric fields could be related to the induced spectral power below approximately 75 Hz. The analysis suggests that bone tissue may be extremely sensitive to induced power levels at or below this frequency, as amplitude variations of less than a factor of two within this range correspond to significantly different bone remodeling responses. The analysis also suggests that bone tissue may be strongly frequency selective, with bone capable of responding specifically to induced power in this osteogenic frequency band, even though the band includes less than 0.1% of the total induced power. As normal functional activity generates strain components encompassing this osteogenic frequency band, a distinct frequency selectivity may indicate that the tissue response is tuned to a specific endogenous stimulus. A detailed characterization of the frequency response of bone tissue could well point to the primary source for the control of the cells responsible for functional adaptation in the skeleton. PMID- 2232824 TI - The role of a thymus-pineal axis in an immune mechanism of aging. AB - The Immune Theory of Aging cannot explain the cause of immune decline. It is hypothesized that the pineal gland acting in utero and during neonatal life in altricial mammals serves as a component of the immune system. Evidence in support of the presence of a thymus-pineal axis is presented. It is postulated that the pineal gland carries a considerable burden of immunological defense during maturation of the thymus, and also acts in the programming of the immune system. By relating thymus and immune function to the pineal and its known role as a neuroendocrine transducer for the entrainment and control of biorhythms, a consilence is developed between the role of the immune system in senescence and the pineal function in biorhythmicity. The relationships developed thus permit an extension of the immune theory as regards causative mechanisms. PMID- 2232826 TI - Effects of exercise and chills on entropy production in human body. AB - Entropy flows and changes of entropy content for naked subjects in the respiration calorimeter in exercise and chills are calculated from the energetic data given by Hardy et al. (1938, J. Nutr. 16, 477) and Du Bois (1939, Bull. N.Y. Acad. Med. 15, 143). By use of these values, entropy productions in the human body in exercise and chills are estimated. The entropy production in mild exercise is 1.5-2.4 times as great as that in basal conditions. The entropy production in violent exercise is six to eight times as great as that before exercise. The entropy production in chills in cold environments is about twice as large as that in basal conditions. The entropy production in a malarial chill is about four times of that in normal subjects. These increases in entropy production will be due to the increase in heat production within the body. It seems that there is a parallel between energy and entropy viewpoints for human physiology. PMID- 2232825 TI - Preferential ligand binding to multi-state acceptor systems: the unexplored paradox of acceptor self-association that is ligand-mediated but detrimental to ligand binding. AB - Consideration is given to the interactions of ligand with self-associating acceptor systems for which preferential ligand binding is an ambiguous term, in that the acceptor species with greater affinity for ligand possesses relatively fewer binding sites. A paradoxical situation wherein ligand-mediated self association is seemingly detrimental to ligand binding is shown to be the predicted outcome for a transient range of ligand concentrations. This outcome reflects the existence of a critical point in the dependence of the extent of acceptor self-association upon ligand concentration that coincides with a cross over point of ligand-binding curves for different, fixed total concentrations of acceptor. By classical differentiation methods the conditions for the existence of these critical points are established not only for two-state acceptor systems but also for three-state acceptor systems in which the ligand-binding form of monomer also undergoes reversible isomerization to an inactive state. Similar procedures are used to comment upon the forms of binding curves for the three state acceptor systems, the Scatchard representations of which may exhibit as many as three critical points (two maxima and a minimum). This delineation of quantitative expressions for critical points and other distinctive features associated with the conflicting interplay of ligand-binding and self-association behaviour should provide a more definitive means of characterizing systems with one acceptor state the preferred binding form on affinity grounds but with the other the preferred state from the viewpoint of binding-site numbers. PMID- 2232827 TI - The mechanical behaviour of cell membranes as a possible physical origin of cell polarity. AB - The mechanical behaviour of a closed layered membrane enclosing a structureless interior is considered. The shape of such an object in flaccid conditions is determined theoretically by assuming that it corresponds to the minimum value of the membrane bending energy. The symmetry breaking properties of this system are revealed. It is suggested that a continuous transition from an axisymmetrical shape involving mirror symmetry with regard to the equatorial plane of the object to the shape with polar asymmetry could be the primary event in establishing cell polarity. PMID- 2232828 TI - Adventures in surgery. PMID- 2232829 TI - Rupture of thoracic aorta caused by blunt trauma. A fifteen-year experience. AB - During the 15 years from 1971 through 1985, 114 patients with rupture of the thoracic aorta caused by blunt trauma were admitted to the Shock Trauma Center of the Maryland Institute for Emergency Medical Services Systems. Mean age was 31.3 years (range, 15 to 80). Ninety were male and 24 were female, a 3.75:1 ratio. Of the 114, 89 (78.1%) survived initial resuscitation in the admitting area. Twenty five of the 89 initial survivors (28.1%) died during or after surgical repair. Paraplegia occurred in 11 of the 78 operating room survivors (14.1%). Further analysis was done of the 83 patients admitted in the 10-year period from 1976 through 1985. Mean Injury Severity Score, excluding aortic injury, was 18.2. Twenty-five of the 83 (30.1%) died during resuscitation in the admitting area or operating room. Seven others died during surgical repair and 12 died postoperatively, leaving 39 survivors (39/83 [47%] of total admissions and 39/58 [67.2%] of survivors of resuscitation). Paraplegia/paresis developed postoperatively in six of 34 (17.6%) cases involving shunt and four of 17 (23.5%) without shunt. Other major complications occurred in 21 of the operating room survivors. Statistically significant risk of death or major complication was associated with female sex, higher Injury Severity Score, lower admission blood pressure, larger hemothorax on admission, less qualified surgeon, major operation before aortic repair, use of shunt, and transfer directly from scene of injury. There was no advantage in this series to using or not using a shunt in preventing paraplegia. Mortality rates are realistic for a highly developed trauma system. Better techniques are needed to manage exsanguination and prevent paraplegia. PMID- 2232830 TI - Repair of transposition of the great arteries with intact ventricular septum and left ventricular outflow tract obstruction. AB - Repair of transposition of the great arteries in patients with intact ventricular septum and fixed left ventricular outflow tract obstruction has been restricted to atrial baffle procedures, with or without attempts to relieve or bypass the left ventricular outflow obstruction. However, the suboptimal results of these procedures, coupled with excellent functional results with the arterial switch operation in patients without obstruction, has made anatomic correction the goal in repairing these anomalies. We report a technique for the anatomic correction of transposition of the great arteries, intact ventricular septum, and fixed left ventricular outflow tract obstruction. Its consideration in these difficult cases is advocated. PMID- 2232831 TI - Extended ex vivo preservation of the heart and lungs. Effects of acellular oxygen carrying perfusates and indomethacin on the autoperfused working heart-lung preparation. AB - The autoperfused working heart-lung preparation has been proposed as a method for long-term heart-lung preservation. We investigated the effects of acellular oxygen-carrying perfusates (study 1) and the effect of donor pretreatment with indomethacin (study 2) on the working ex vivo heart-lung block. In study 1 perfusion with stroma-fee hemoglobin resulted in significantly reduced survival (118 +/- 46 minutes) compared with autologous blood (561 +/- 125 minutes, p less than 0.05) or perfluorocarbon (438 +/- 114 minutes, p less than 0.05). Decrease in survival with stroma-free hemoglobin perfusate is associated with a marked decrease in left ventricular performance and a significant increase in pulmonary vascular resistance. Perfusion with autologous blood is associated with a significant increase in pulmonary vascular resistance after 240 minutes of explantation, which is significantly delayed by perfusion with perfluorocarbon. Perfusion for 6 hours with blood pretreated with indomethacin (study 2) resulted in a decrease in the concentration of prostacyclin and thromboxane A2 metabolites but an increase in the prostaglandin/thromboxane A2 metabolite ratio. This is associated with abrogation of the increase in pulmonary vascular resistance (12,787 +/- 1682 dynes/sec/cm-5, T = 0; 13,134 +/- 2654 dynes/sec/cm-5, T = 360 minutes) observed in preparations perfused with autologous blood (13,194 +/- 1942 dynes/sec/cm-5, T = 0; 24,768 +/- 3325 dynes/sec/cm-5, T = 360 minutes, p less than 0.05). We conclude that alteration of the cellular and humoral components of autologous blood may prove advantageous for increasing the utility of the autoperfused working heart-lung preparation as a preservation technique. PMID- 2232832 TI - Importance of acid-base strategy in reducing myocardial and whole body oxygen consumption during perfusion hypothermia. AB - During induced hypothermia with cardiopulmonary bypass, acid-base management usually follows one of two strategies: the so-called ectothermic or alpha-stat strategy, in which the pH of the arterial blood increases 0.015 pH units for every degree Celsius decrease in body temperature, or the pH-stat strategy, in which pH remains 7.4 at all temperatures. It has been assumed that oxygen consumption decreases approximately equally during hypothermia with either strategy, although there are biochemical reasons to hypothesize that oxygen consumption would be better maintained with the alpha-stat strategy. We also hypothesized that venous oxygen tension would be lower with the more alkaline alpha-stat strategy than with the pH-stat acid-base strategy, because of the Bohr effect. We tested these hypotheses by placing 10 anesthetized immature domestic pigs on cardiopulmonary bypass. We measured whole body oxygen consumption and myocardial oxygen consumption. Control measurements were made at 37 degrees C. Then the animals were cooled to 27 degrees C and the measurements were repeated. The alpha-stat strategy (pH 7.554 +/- 0.020 at 27 degrees C) was used in five animals and five animals received pH-stat management (pH 7.409 +/- 0.012 at 27 degrees C). Whole body and myocardial oxygen consumption rate decreased in both groups, but more so in the alpha-stat animals than in the pH-stat animals. The unexpectedly high oxygen consumption in the pH-stat animals also resulted in a lower than expected venous oxygen tension. Thus the effect of hypothermia in reducing oxygen consumption was less pronounced with pH-stat acid-base management. PMID- 2232833 TI - Effect of supplementing cardioplegic solution with deferoxamine on reperfused human myocardium. AB - Fourteen randomized patients undergoing myocardial revascularization were divided into group A standard hypothermic cardioplegic solution) and group B (the same cardioplegic solution supplemented with deferoxamine 1000 mg/L). In all patients myocardial biopsy specimens were obtained before ischemia and during reperfusion and were assessed for chemiluminescence (to indirectly determine oxygen-free radical activity) and for electron microscopic studies. Chemiluminescence in group A showed a photoemission of 36.5 +/- 1.5 cpm/mg protein X10(-3) for the preischemia samples and 72 +/- 5.7 cpm/mg protein X10(-3) for the reperfusion samples (p less than 0.01). In the patients who received deferoxime (group B), values for chemiluminescence for preischemia and reperfusion samples were not significantly different. Electron microscopic studies showed a significant increase in grade 4 (severely damaged) mitochondria in reperfusion biopsy specimens from both groups as compared with preischemia samples. However, reperfusion samples from group B showed a better preservation of myocardial cells with marked reduction of grade 4 (severely damaged) mitochondria. These results support the hypothesis that oxygen-free radicals are responsible in part for the production of reperfusion injury in the human heart. They suggest that this mechanism may be at least partially controlled by adding an iron chelating agent such as deferoxime. PMID- 2232835 TI - Studies of controlled reperfusion after ischemia. XVII. Reperfusion conditions: controlled reperfusion through an internal mammary artery graft--a new technique emphasizing fixed pressure versus fixed flow. AB - This study tests the usefulness of delivering a controlled reperfusate through an internal mammary graft after acute ischemia by applying a percutaneous technique of mammary artery cannulation and compares reperfusion at fixed pressure versus fixed flow. METHODS: Twenty-one dogs underwent 2 hours of ligation of the left anterior descending coronary artery followed by regional controlled revascularization on total vented bypass. A reperfusion catheter was introduced percutaneously from the brachial artery into the internal mammary artery. Five dogs received normal blood reperfusion at 50 mm Hg pressure, and eight dogs received a regional blood cardioplegic reperfusate at 50 mm Hg before reperfusion with normal blood. Eight additional dogs received regional cardioplegia at 30 ml/min for 20 minutes. Coronary vascular resistance, segmental shortening (ultrasonic crystals), tissue water content, and histochemical damage (triphenyltetrazolium chloride stain) were assessed. RESULTS: Reperfusion with normal blood increased coronary vascular resistance progressively to 62% above initial values (p less than 0.05) and failed to restore regional contractility (9% +/- 6% systolic shortening, p less than 0.05). In contrast, coronary resistance remained low throughout blood cardioplegic reperfusion at fixed pressure and the reperfused muscle recovered immediate contractility (73% systolic shortening, p less than 0.05). Controlled reperfusion at a fixed flow rate resulted in pressure that ranged from 30 to 80 mm Hg, slightly less recovery of systolic shortening (57%), and less return of contractile reserve (81% versus 114%, p less than 0.05). Regional blood cardioplegic reperfusion limited edema formation (79.5 versus 82% water content, p less than 0.05) and histochemical damage (11% versus 50% area of necrosis/area at risk, p less than 0.05). CONCLUSION: An internal mammary artery graft can be used effectively in the setting of acute ischemia if a controlled blood cardioplegic reperfusate is delivered through it to ensure limitation of histochemical damage, low reflow phenomenon, and restoration of immediate segmental contractility. Controlled pressure reperfusion seems superior to fixed-flow reperfusion. A technique is described that may allow preoperative insertion of the reperfusion catheter in the internal mammary artery in the catheterization laboratory. PMID- 2232834 TI - The effects of dopamine on myocardial functional recovery after reversible ischemic injury. AB - Dopamine frequently is used to improve cardiac performance after acute myocardial ischemia. Inotropic agents, however, increase myocardial oxygen demand and could potentially delay recovery from ischemic injury. To evaluate this problem, we studied eight chronically instrumented dogs in the conscious state and performed two 15-minute coronary occlusions 48 hours apart. After one of the occlusions, either dopamine (15 micrograms/kg/min) or saline placebo was administered intravenously from 1.0 to 1.5 hours of reperfusion. The alternative infusion was given during the second study. Preload recruitable work area, the area beneath the stroke work versus end-diastolic length relationship, was used to assess intrinsic myocardial performance. Ischemia decreased preload recruitable work area to 13% of control after both occlusions. After reperfusion, a 30-minute dopamine infusion acutely increased myocardial function nearly threefold as compared with placebo. Myocardial performance after dopamine administration, however, was significantly depressed compared with placebo throughout the remaining 24 hours of reperfusion (p less than 0.01). These data indicate that dopamine may impair functional recovery after ischemic myocardial injury and suggest that inotropic interventions should be used in this setting only when absolutely indicated. PMID- 2232836 TI - Studies of controlled reperfusion after ischemia. XVIII. Reperfusion conditions: attenuation of the regional ischemic effect by temporary total vented bypass before controlled reperfusion. AB - This study tests the hypothesis that total vented bypass can attenuate the regional ischemic effect during a defined time interval before controlled blood cardioplegic reperfusion. Thirty-three dogs underwent 2 or 4 hours of occlusion of the left anterior descending coronary artery and then received a regional blood cardioplegic reperfusate on total vented bypass. Cardiopulmonary bypass and reperfusion were started after 2 hours of ischemia in eight dogs, and after 4 hours of ischemia in 25 others. Among the 25 dogs, seven had total vented bypass started after the first 2 hours of the 4 hours of regional ischemia. Segmental shortening (ultrasonic crystals), tissue water content (wet/dry weight), and histochemical damage (triphenyltetrazolium chloride stain) were assessed 2 hours after reperfusion. Dogs reperfused after 2 hours of ischemia recovered 73% +/- 8% of control systolic shortening and sustained only 11% triphenyltetrazolium chloride nonstaining. Dogs undergoing 4 hours of regional ischemia, but with total vented bypass 2 hours before reperfusion had improved recovery of systolic shortening (49% versus 31%, p less than 0.05), limited epicardial edema (79.6% versus 81.1% water content, p less than 0.05), and reduced histochemical damage (24% versus 39% triphenyltetrazolium chloride nonstaining, p less than 0.05). These findings imply that institution of total vented bypass during ischemia attenuates the infarct process, increases regional recovery of contractility, limits edema and restricts histochemical damage, and may be a useful adjunct to myocardial salvage when controlled reperfusion can be provided. PMID- 2232837 TI - Intraoperative transesophageal color-coded Doppler echocardiography for evaluation of residual regurgitation after mitral valve repair. AB - Because mitral valve competence after mitral valve reconstruction is awkward to assess during this procedure, we evaluated in this respect transesophageal color coded Doppler echocardiography in 23 patients undergoing mitral valve reconstruction for severe mitral regurgitation. Transesophageal echocardiographic examinations were performed after induction of anesthesia but before sternotomy (baseline), after mitral valve repair before decannulation, and at sternal closure, all at similar mean aortic pressure and echocardiographic instrument settings. The degree of mitral regurgitation by transesophageal color Doppler flow mapping was visually quantified on a 5-point scale (0 to 4), pending the left atrial extent of the regurgitant jet. This was compared with the degree of mitral regurgitation by left ventricular cineangiography performed within several weeks after operation and also visually quantified on a 5-point scale (0 to 4), with use of the right anterior oblique projection. There was good correlation between the two methods (r = 0.83; p less than 0.001). We conclude that residual mitral regurgitation, as assessed by transesophageal color flow mapping in the operating room, highly correlates with the ultimate mitral regurgitation by cineangiography. Therefore transesophageal echocardiography can be helpful for evaluation of mitral valve competence during mitral valve reconstruction, and hence, in case of repair failure, allow valve replacement in the same surgical session, thus avoiding reoperation. PMID- 2232838 TI - Mitral valve replacement in the first year of life. AB - From 1973 through 1987 25 patients underwent mitral valve replacement in the first year of life for mitral stenosis and mitral regurgitation. The patients with mitral stenosis included two with mitral arcade, two with supravalvular mitral stenosis with hypoplastic mitral valve, and one with parachute mitral valve. Included in the group of patients with mitral regurgitation were 12 with atrioventricular canal defect, six with chordal and leaflet defects, one with Marfan's syndrome, and one with bacterial endocarditis. Prostheses included 12 Bjork-Shiley (17 mm), seven St. Jude Medical (19 mm in four, 21 mm in three), five stent-mounted dura mater valves (12 mm to 16 mm), and one porcine xenograft (19 mm). In four patients the valves were placed in the left atrium in a supraannular location. There were nine operative (atrioventricular canal defect seven, mitral regurgitation two) and five late (atrioventricular canal defect four, mitral stenosis one) deaths, giving actuarial 1- and 5-year survival rates of 52% and 43%, respectively. All 6 patients with tissue valves died; the four with supraannular mitral valve replacement survived. Since 1983 operative mortality has been reduced to 0% (70% confidence limits 0% to 24%). Nine patients required a second mitral valve replacement for prosthetic stenosis 5 to 69 (mean 30) months after the original mitral valve replacement (one operative death). Because of improvements in repair of atrioventricular canal defect in infancy, the need for mitral valve replacement at atrioventricular canal defect repair has decreased. Although valvuloplasty has been advocated for repair of congenital mitral valve disease and is applicable in some infants with mitral regurgitation, mitral valve replacement is frequently unavoidable for congenital mitral disease and can now be accomplished at a low operative risk, even when the prosthesis has to be positioned supraannularly. PMID- 2232840 TI - Aortic replacement with composite grafts created with a sutureless intraluminal ringed prosthesis. AB - From 1980 to 1988, 30 patients from a total population of 123 recipients of sutureless grafts (24%) have required aortic reconstruction with a composite ringed graft. Replacement of the ascending aorta was required in 12 patients, of the aortic arch in six patients, of the descending aorta in two patients, of the thoracoabdominal aorta in two patients, and of the abdominal aorta in eight patients. Eight patients (27%) needed an emergency operation at the time of admission. No patients had permanent neurologic or renal deficits. There was no evidence of pseudoaneurysm formation, graft erosion, graft migration, or aortic bleeding in the postoperative period. Two operative deaths (7%) occurred, both in patients undergoing arch reconstruction. Composite grafts can be created that vary in length and shape, incorporate different graft materials, and accommodate the aorta and its branches. The ability to modify the sutureless prosthesis to suit the disease encountered at operation allows the quickest repair with the least chance of anastomotic complication. PMID- 2232839 TI - Endotoxins in cardiopulmonary bypass. AB - Endotoxins are biologically active substances derived from the cell wall of degraded gram-negative bacteria. Since sterile water may also contain large amounts of endotoxins, these are easily introduced into the manufacturing processes of technical medical material, such as the extracorporeal components used in cardiopulmonary bypass. In hemodialysis, the presence of endotoxins has been related to untoward effects in patients. Using the limulus amebocyte lysate test, we determined the serum concentration of endotoxin in 42 patients undergoing coronary bypass operations. The values increased during cardiopulmonary bypass, exceeding the normal range of 0 to 20 ng/L in 10 patients with a maximum of 82 ng/L, which probably indicates endotoxin release from the extracorporeal equipment. We found no obvious relation to postoperative morbidity. The endotoxin levels of this study are considerably lower than those reported in two other studies of patients having cardiopulmonary bypass. This might be due to less intraoperative contamination but possibly also to differences in analytic methods. PMID- 2232841 TI - A flexible sutureless intraluminal graft that becomes rigid after placement in the aorta. AB - A new sutureless intraluminal graft has been developed with a ring made of a coiled, overlapping, stainless steel spring with ratchets in one overlapping end. This graft is flexible during insertion but becomes rigid after proper intraaortic placement as the spool is dilated and the ratchest lock into position. The new graft was implanted in 10 dogs and was evaluated histologically and angiographically at various intervals. No ring dislodgment, aortic rupture, stenosis, or aneurysmal dilation was observed. The flexible component of this graft allows it to be introduced and secured in place easily and provides a technical advantage compared with the clinically used rigid intraluminal graft. PMID- 2232842 TI - Invited letter concerning: simulated left ventricular aneurysm and aneurysm repair in swine. PMID- 2232843 TI - Questions regarding internal mammary hypoperfusion. PMID- 2232844 TI - Revascularization with the right gastroepiploic artery in Kawasaki's disease. PMID- 2232845 TI - Thrombosed CarboMedics mitral valve prosthesis. PMID- 2232846 TI - Right ventricular outflow tract obstruction in simple and corrected transposition of the great arteries. PMID- 2232847 TI - GM-CSF incubation prior to treatment with cytarabine or doxorubicin enhances drug activity against AML cells in vitro: a model for leukemia chemotherapy. AB - We studied the effect of preincubation with recombinant GM-CSF on the activity of cytarabine and doxorubicin against clonogenic acute myeloid leukemia cells (CFU AML). Leukemia cells from seven persons with AML, three myeloid cell lines (HL60, KG1, K562) and two control cell lines (U937, MOLT3) were tested. Preincubation with GM-CSF (0.01-0.1 microgram/ml) increased DNA synthesis as measured by tritiated thymidine incorporation and intranuclear Ki67 expression in cells from six persons with AML and in HL60 cells. Leukemia cells preincubated with GM-CSF for 6-48 h were exposed to cytarabine (2-200 micrograms/ml) or doxorubicin (0.01 0.1 microgram/ml) for 3 h and CFU-AML assayed. This approach further reduced CFU AML in samples from six persons with AML and in HL60 and KG1 cells compared to cells not preincubated with GM-CSF prior to drug treatment. In most instances, reduced CFU-AML correlated with GM-CSF induced DNA synthesis. These data suggest a possible strategy of GM-CSF pretreatment to increase anti-leukemia efficacy of chemotherapy in AML. PMID- 2232848 TI - Biochemical characterisation studies on a leukocyte alloantigen expressed with high frequency in leukaemia patients. AB - In this report we describe, using a previously characterised monoclonal antibody (NC-2), the biochemical characteristics of a human leukaemia-associated alloantigen. Two proteins with molecular weights of 50 kDa and 15 kDa were immunoprecipitated from 125I surface labelled HL-60 cells. Both proteins appeared to be sensitive to digestion with trypsin, the 50 kDa protein in particular. Treatment with glycopeptidase F indicated the presence of N-linked oligosaccharides, whereas treatment with neuraminidase had no effect on the mobility of the antigens in SDS-PAGE indicating the absence of detectable sialic acid residues. Sensitivity to glycopeptidase F indicates that the reacting antigens are glycoproteins in nature. The antibody reacts with a range of normal tissues and appears to be associated with cytoplasmic granules in HL-60 cells. PMID- 2232850 TI - Response to intermediate and standard doses of IFN-beta in hairy-cell leukaemia. AB - Thirteen hairy-cell leukaemia patients were treated with IFN-beta (6 X 10(6) IU/m2) for 7 days, alternate weeks, for three cycles. IFN-beta was then continued at the same dose twice a week for 24 weeks. Treatment was discontinued in 2 non responders and 2 partial responders (1 haem PR, 1 path PR) because of complications unrelated to IFN. The objective response in the nine patients who completed therapy was 66% (1 CR, 3 path PR and 2 haem PR); 2 patients achieved MR. Responses lasted from 5 to 45+ months. Four newly diagnosed patients and 3 in relapse after discontinuation of IFN-beta therapy (6 X 10(6) IU/m2), were treated with a lower dose of IFN-beta (2 X 10(6) IU/m2). The objective response to this dose was 57% (3 path PR, 1 haem PR). Another patient obtained MR. No patient has relapsed 6-12 months after therapy discontinuation. IFN-beta was well tolerated, especially at the lower dose and no chronic toxicity was observed. Therefore IFN beta may be suggested as an alternative treatment for HCL. PMID- 2232849 TI - A study of multidrug resistance and cell kinetics in a child with near-haploid acute lymphoblastic leukemia. AB - Marked hypodiploidy is found in a small group of patients with acute lymphoblastic leukemia (ALL) and is associated with very poor prognosis. Cells from a patient with near-haploid ALL (karyotype: 27 XY, DNA index = 0.5) were investigated by multiparameter flow cytometry at relapse and at multiple time points during reinduction chemotherapy. The cell cycle of these near-haploid leukemic blasts and their chromatin structure was studied by acridine orange (AO) DNA/RNA flow cytometric assays. Most leukemic cells were in "G0", and no recruitment of the bone marrow cells into the G1 phase of the cell cycle was found during reinduction therapy with high dose cytosine arabinoside. After two cycles of chemotherapy, the patient achieved clinical remission, but persistent haploid cells were identified by flow cytometry and he relapsed after 8 weeks and died after 16.7 weeks. The leukemic blasts expressed very high levels of a 180 kd p-glycoprotein associated with multidrug resistance and daunomycin efflux could be blocked by verapamil. Expression of gp 180 and the verapamil effect on intracellular daunomycin concentration indicate multidrug resistance. We conclude that cell kinetic quiescence and multidrug resistance may both be factors responsible for the poor prognosis of this patient with near-haploid ALL. Further studies of this patient group should determine if these mechanisms are indeed responsible for the poor prognosis associated with near-haploid leukemia. PMID- 2232851 TI - The monitoring of acute leukemia patients: Part 1. Basic morphometric characteristics of bone marrow blast cells in acute lymphoblastic leukemia. AB - Morphologic types L1 and L2 (FAB) of acute lymphoblastic leukemia were classified by computer morphometry of bone marrow blast cells in 57 patients. Measurements were made on MOP-Videoplan Analyser (Reichert) by means of cell image contouring. The decision rule that had been deduced by us on the basis of multidimensional analysis of variance in two-cell training sets, and the selection of the following combination of the best discriminating features [the discriminant coefficients are in brackets: maximal nuclear diameter (-0.338), nuclear perimeter (-6.145), cell area (-0.044), nuclear area (1.007), relative nucleoli eccentricity (-0.279), cytoplasmic/nuclear relation (-5.920) and integral nucleoli area (-0.640)] were used for computer classification of L1 and L2 blast cells. The threshold score for discriminant function in this case was -117.766. Complete clinical remission rates in L1 ALL appeared to be higher than in L2 but remission duration in those groups did not differ significantly. The morphometric parameters of leukemic cells seem to characterize their maturity or their position in cell cycle phases and may be used in acute leukemia patient monitoring. PMID- 2232852 TI - Lineage non-specific down regulation of P210bcr/abl in the CML cell line, KU-812 F, during differentiation. AB - CML cell line, KU-812-F, originally established from a patient with Philadelphia chromosome-positive chronic myelocytic leukemia has maintained the ability to differentiate into both granuloid (basophilic) and erythroid lineages. The expression of P210bcr/abl in KU-812-F cells during differentiation was studied by immunoblotting and immunoprecipitation. Immunoblotting with anti-phosphotyrosine sera revealed the down-regulation of P210bcr/abl in both granuloid and erythroid lineages. Immunoprecipitation with anti-abl antibodies of 35S-methionine-labelled cells revealed a reduced rate of synthesis of P210bcr/abl protein. Cytotoxic agents that caused growth inhibition of the cells did not alter the expression of P210bcr/abl. These results indicate that the down regulation of P210bcr/abl protein is a lineage non-specific event accompanied by differentiation. PMID- 2232853 TI - B8.7 antigen expression on B-CLL cells and its relationship to the LMW-BCGF responsiveness. AB - In this work, we studied the expression of B8.7 antigen on B lymphocytes from patients suffering from B type chronic lymphocytic leukemia (B-CLL) as well as on non Hodgkin lymphoma cells (NHL). B8.7 is an activation marker, which has been reported to be associated with the capacity of activated B cells to respond to LMW-BCGF. B lymphocytes of 11 out of 22 patients tested were B8.7 positive. With the exception of one case, LMW-BCGF is able to induce DNA synthesis by these cells in the absence of costimulation by anti-mu antibodies (anti-mu Ab). The LMW BCGF dependent proliferation of these malignant cells is inhibited by the anti B8.7 monoclonal antibody (anti-B8.7 MoAb), in the same line as that of normal B cells. These results obtained with monoclonal B cells confirm that the B8.7 molecule is involved in the signalling pathway of the LMW-BCGF. PMID- 2232854 TI - Repression of nuclear lamin A and C gene expression in human acute lymphoblastic leukemia and non-Hodgkin's lymphoma cells. AB - The lamins A, B and C which are differentially expressed during ontogenesis and differentiation are karyoskeletal proteins forming a polymeric meshwork at the inner nuclear membrane. Using Northern blot analyses we investigated the steady state levels of the three lamin specific RNA transcripts in neoplastic cells derived from 16 untreated patients with acute lymphoblastic leukemia (ALL) or non Hodgkin's lymphoma (NHL) and in ALL and NHL established cell lines. Whereas lamin B mRNA was present in all, lamin A and C transcripts were observed in none of the malignant cell samples except one of a common-ALL patient (precursor B-ALL, cytoplasmic mu chain negative). All three lamin mRNAs were detected in normal peripheral blood lymphocytes, however, only after mitogenic stimulation with concanavalin A. Our results provide evidence that expression of lamin A and C is repressed in neoplastic blast cells derived from patients with ALL or NHL and suggest that lamin A and C gene repression is not related to cell proliferation but might be relevant to the differentiated stages of the lymphoid cells in vivo. PMID- 2232855 TI - Neutrophil functions in chronic myeloid leukemia. PMID- 2232858 TI - Methods for estimating release rates during high frequency quantal secretion and for testing such methods. AB - The rate of spontaneous quantal release must be estimated in some investigations of synaptic transmission, even when frequencies are so high that individual quanta cannot be distinguished. An obvious method is to measure the time integrals of the summed MEPPs and then dividing this value by the integral of an average MEPP. The method was tested by recording miniature end-plate potentials (MEPPs) at frog neuromuscular junctions, counting the number of MEPPS, and then adding together records from the same junction to simulate high frequencies. The estimates from the integral method agreed well with the actual counts. The method can readily be used with a microcomputer and does not require stationary data. Methods based on fluctuation analysis were also used to estimate quantal frequencies, but they did not always give good estimates. This was not a thorough test of the fluctuation method, but an example of testing with MEPP data. The integral method might be reasonably reliable, but there are further potential complications, like changes in MEPP size and short-circuiting of the end-plate membrane, which may make it difficult to obtain reliable measurements of high frequency quantal secretion without voltage clamping and protocols that permit measurements of individual MEPCs during the course of the frequency measurements. PMID- 2232857 TI - Age-related features of the resting and P300 auditory evoked responses using the dipole localization method and cortical imaging technique. AB - Two mathematical techniques, the dipole localization method (DLM) and the cortical imaging technique (CIT), are used to analyze the resting and P300 auditory responses in young and old normal volunteers. These methods identify certain age-related features of these evoked responses that are not found by standard topographic methods. These features include the orientation of the P200 resting response, and the laterality of the N120 response, and the eccentricity of the P300 response in the P300 stimulus condition. Theoretical dipole sources and simulated cortical surface maps are also constructed for one normal subject and one psychiatric inpatient and compared. These mathematical methods appear to enhance the discriminating power of traditional electrophysiological measures. PMID- 2232856 TI - An improved system for single unit isolation from multiunit nerve recordings by velocity analysis. AB - A system for recording and decomposition of complex extracellular spike trains by analog computing is presented. Unlike other systems, it is not necessary to establish templates for the analysis. Rather by adjustments of a single knob, the velocity band can be adjusted. The velocity measurement can be made to a precision of better than 1%, where the velocity jitter in individual spikes of a unit becomes apparent. Spike trains on the connective of a stick insect are analyzed which occur during an intersegmental reflex, the CLP reflex. PMID- 2232860 TI - Easily-implantable electrodes for chronic recording of electromyogram activity in small fetuses. AB - A method is described for the construction of simple, robust electrodes suitable for obtaining long-term chronic recordings of electromyogram activity from delicate muscles of small experimental animals. The electrodes are equipped with small, gold-plated barbed tips which have the form of harpoons that may be pushed directly into a muscle, where they remain without being sutured into place. These features greatly facilitate the instrumentation of muscles which are very thin or of limited accessibility. The electrodes have been used successfully to obtain chronic recordings of respiratory muscle activity from early gestation fetal lambs in utero. PMID- 2232859 TI - Fast cyclic voltammetry: improved sensitivity to dopamine with extended oxidation scan limits. AB - Fast cyclic voltammetry at carbon fibre microelectrodes has been used in vitro and in vivo mainly to monitor the release and uptake of dopamine. The 'standard' input voltage waveform (-1000 to +1000 mV, vs. Ag/AgCl, 300 V/s scan rate) has a lower limit of detection for dopamine of about 200 nM. In the present study, the scan rate and cathodic limit (-1000 mV) were kept constant while the range of the anodic scan was altered between 800 and 1400 mV. Extension of the oxidation scan to 1400 mV led to a sevenfold increase in dopamine oxidation current relative to the 'standard' waveform. This was accompanied by a decrease in the dopamine oxidation peak potential. Increased reactant adsorption for both dopamine and DOPAC was the likely cause of enhanced sensitivity. In vivo experiments indicate that, when used with the 1400 mV scan, the carbon fibre electrodes do not poison on contact with brain tissue and can measure dopamine concentrations lower than 50 nM. PMID- 2232861 TI - A technique for controlling the membrane potential of neurons during unit recording. AB - While extracellular unit recordings are technically easier to perform than intracellular recordings, the latter permits control of neuron excitability by changing the membrane potential with steady current passed across the recording micropipette. Utilizing an intracellular amplifier with bridge circuit for the passage of low current (1-10 nA), we show that an extracellular recording micropipette of high resistance (5-20 M omega) can be used in a similar fashion while monitoring single unit activity in the rat brain. This procedure allows fine control of two neuronal mechanisms which are voltage-sensitive: action potential discharge and regenerative bursting. Control of a neuron's membrane potential expands the capabilities of unit recording in the study of evoked synaptic input and bursting behaviour. It can also facilitate classification of neurons based on their firing characteristics. PMID- 2232862 TI - Preservation of the NMDA response of neurons acutely dissociated from the mature guinea pig hippocampus. PMID- 2232863 TI - Dye-induced photopermeabilization and photodegeneration: a lesion technique useful for neuronal tracing. AB - Using as a neural system the fly retina, which is visually accessible in vivo, we describe a lesion technique that takes advantage of the photodynamic damage produced by extrinsic dyes. Contrary to the photo-inactivation technique described by Miller and Selverston (1979), this technique does not involve intracellular injection, since the dye is applied to the extracellular space of the tissue. This treatment was found to trigger neuronal degeneration and cell permeabilization in fly photoreceptor neurones. We coined the names 'photodegeneration' and 'photopermeabilization' for these two phenomena. While the technique can be used to delete given neurones from the neural circuit after several days' survival time, it was found to produce adequate cytoplasmic labelling for anatomical studies with both light and electron microscopy. Since the area occupied by the degenerating cells is restricted to the light spot imaged onto the nervous tissue, the resolution with this lesion technique can range from single cells to whole neuronal populations. The remarkable precision of the 'photolesions' produced in this way makes this technique a powerful tool for physiological and anatomical investigations on real neural networks, whenever these can be made optically accessible in vivo or in situ. PMID- 2232864 TI - Cresyl violet: a red fluorescent Nissl stain. AB - Cresyl violet is widely used by neurobiologists to visualize Nissl substance in bright-field microscopy. Here we describe a method for using this dye as a red fluorescent Nissl stain. Unlike the bright-field staining technique, fluorescent cresyl is compatible with other fluorescent dyes and tracers, such as fluorescein, Fluoro-Gold and Fast Blue. The procedure requires only minor modifications of routine bright-field cresyl staining, the most significant being dilution of the stain. Thus, fluorescent red cresyl violet is simple to implement and may be of general use in fluorescence microscopy. PMID- 2232865 TI - Neuron simulations with SABER. AB - Computational models can provide critical tests of hypotheses of neuronal function. These models are essential for dealing with the complications of time- and voltage-dependent (active) ionic conductances. Commercial circuit analysis programs have been useful tools for this work. We report our experience modelling biophysically realistic membrane properties with SABER (Analogy, Inc.), a new general purpose simulator. SABER allows construction of models with arbitrary membrane properties. This is a major advantage over similar programs (e.g. SPICE), which are limited to a predefined library of electronic components. The empirically determined equations that describe rate constants, ionic conductances, currents, and concentration shifts can be translated directly into model elements ('templates') written in C-like code. We describe the development of SABER models that simulate a synapse and an action potential. PMID- 2232866 TI - A new medium for in vitro peripheral nervous tissue myelination without the use of antimitotics. AB - This paper describes a new medium which promotes myelin formation in cultures of rat dorsal root ganglia, and controls fibroblast proliferation. The medium, medium 'M', contains D-valine rather than L-valine and is added to cultures after seven days in vitro (DIV). The presence of D-amino acid oxidase in Schwann cells and neurons permits these cells to convert D-valine to L-valine, an essential amino-acid. Fibroblasts however lack D-amino acid oxidase but as some L-valine is present in the fetal calf serum component of medium 'M' those fibroblasts already present in the cultures by day 7 are maintained. Further fibroblast proliferation is however inhibited. The use of medium 'M' does not require the use of specific antimitotic agents making it cheaper and quicker to obtain myelinated cultures than with previous methods. The medium results in widespread myelin formation by 21 DIV. Cultures may be grown on plastic or collagen coated glass coverslips. PMID- 2232867 TI - Chemical brain stimulation as a means to circumvent electrical stimulation artefacts in single-unit recording studies of evoked vocalization. AB - This study describes a combined single-unit recording/chemical brain stimulation technique that proved to be helpful in cases in which the behavior pattern to be studied electrophysiologically is difficult to elicit repetitively by external stimuli, but is easily obtained by brain stimulation. The advantage of this technique over electrical elicitation of the behavior is the avoidance of periodic stimulation artefacts that make detailed analyses of pattern-correlated neuronal activity often impracticable. Out of a number of substances tested for chemical brain stimulation, kainic acid proved to be the most effective one. With a single injection of 50 ng (in 200 nl water) into the periaqueductal gray of the squirrel monkey up to 6480 vocalizations could be obtained over a period of 65 min. Up to 22 injections could be made at this dose before a site became unresponsive. PMID- 2232868 TI - A simple, inexpensive method of monitoring brain temperature in conscious rodents. AB - A method was developed to monitor brain temperature in conscious, unrestrained rodents. A commercially available thermocouple microprobe was modified so that it could be screwed firmly into a guide cannula that had been stereotactically implanted in the brain. Because the microprobe remains firmly in place, it is possible to record continuously for several hours from a single animal. Because the microprobe is easily removed, one can also record intermittently from several animals at once. The necessary equipment is relatively inexpensive and the modified microprobe can be sterilized and reused indefinitely. This method has proved especially useful for monitoring brain temperature during and after transient cerebral ischemia, an insult that destroys CNS neurons in a temperature sensitive fashion. PMID- 2232871 TI - Miniaturized optoelectronic system for telemetry of in vivo voltammetric signals. AB - In vivo voltammetry is an electrochemical technique that uses carbon fiber microelectrodes stereotaxically implanted in brain areas to monitor monoamine metabolism and release continuously, in freely moving animals. Electric wires connect the polarograph to the animal. A wire-less transmission system (optoelectronic transmission, OPT) of voltammetric signals is described here. It uses infrared diffused light, exploiting the diffusion of the transmitted light over walls and ceiling towards a receiver. The transmission system consists of a main unit and a satellite unit (40 x 30 x 5 mm) positioned on the animal's back. Voltammetric recordings obtained by the classical system (with wires) and by OPT are well defined and almost identical in shape. The power supply is provided by two thin lithium batteries (+/- 3V) that can record for up to 20 h. OPT permits detailed behavioral observations since the animal can be left free to move in a spacious environment. Voltammetry using OPT allows simultaneous recording of neuronal firing activity as well as electroencephalographic recordings (EEG) since there is no cross-talk between the circuits used. The results illustrate the reliability and usefulness of this wire-less transmission system for studying relationships between neurochemical, behavioral and electrophysiological activities. PMID- 2232870 TI - Monosodium urate test: a new analgesic test by crystal-induced monoarthritis in rats. AB - The analgesic effects of various agents were evaluated in knee joint monoarthritic rats where arthritis was induced by monosodium urate (MSU) crystals injected into the knee joint cavities. The weight supported by each hind limb was measured quantitatively using pressure transducers, which revealed dose-dependent recovery produced by various analgesics including morphine but no changes in value by sedatives such as chlorpromazine. Relative potency obtained from the value of ED50 of each analgesic agent was congruent with that in clinical use. The MSU test may be quite suitable for quantitative and objective evaluation of the analgesic effects of various agents, particularly for spontaneous and tonic pain. PMID- 2232869 TI - A simple quantitative dot-immunobinding assay for glial and neuronal marker proteins in SDS-solubilized brain tissue extracts. AB - Immunoassays for quantitative determinations of the S-100 protein, the glial fibrillary acidic protein, the neuron specific enolase and the neurofilament proteins with molecular weight of 68 and 200 kDa in hot SDS sonicated rat brain extracts have been developed and characterized. The assays utilize a dot immunobinding technique, poly- or monoclonal antibodies and 125I-protein A. The SDS-sonication procedure was not found to affect the radioactivity recovery in the assay of the soluble S-100 protein or the neuron specific enolase. All 5 antigens can be measured with a within-assay variance below 10%. Even at a coefficient of variation less than or equal to 5%, the working ranges are approximately 30-100-fold with regard to the different antigens. It was found that gelatin-coated nitrocellulose membranes considerably increase the recovered radioactivity in the assay of the purified bovine S-100 protein, possibly by protein-protein interaction. This effect was not observed when SDS-sonicated rat brain extracts were assayed. The assay appears to be reproducible, convenient and rapid, and provides a high degree of precision in the determination of large number of samples. PMID- 2232872 TI - A slope-based approach to spike discrimination in digitized data. AB - A spike discrimination algorithm based on the analysis of spike up- and down slopes can advantageously replace those based only on amplitude with a minimal increase of programming complexity and processing time. Such an algorithm was developed to sort muscle depolarizations from nerve spikes in electromyograms in insects. It could also be used to sort spikes according to their direction of travel in bipolar recordings from mixed nerves. PMID- 2232873 TI - Law and aging. PMID- 2232874 TI - Realism, law and aging. PMID- 2232875 TI - Assessing decision-making capacity. PMID- 2232876 TI - The values history: an innovation in surrogate medical decision-making. PMID- 2232877 TI - Trends in guardianship reform: implications for the medical and legal professions. PMID- 2232878 TI - Refusals of medical care in the home setting. PMID- 2232879 TI - Assuring quality of care for the elderly. PMID- 2232880 TI - Legal issues in nursing home admissions. PMID- 2232881 TI - The fear of liability and the use of restraints in nursing homes. PMID- 2232882 TI - Financial planning for health care in older age: implications for the delivery of health services. PMID- 2232883 TI - State of the law: nursing homes. PMID- 2232885 TI - BCR-ABL and BCR proteins: biochemical characterization and localization. AB - The Philadelphia translocation results in the expression of a family of chimaeric proteins in which a portion of the bcr protein is fused to c-abl protein. Using antibodies which recognize different portions of the bcr gene and abl gene products we have compared the normal bcr products with their chimaeric counterparts. We first conclude that the enhanced kinase activity of the rearranged bcr-abl products (p210 and p190) is recovered almost exclusively from the cytosolic fraction. This methodology was confirmed by the demonstration that in cells transformed by the Abelson murine leukemia virus (A-MuLV) the gag-abl kinase activity was recovered equally from the membrane and cytosolic fractions, in agreement with previous studies. To determine whether the distribution of kinase activity reflected the bulk distribution of the bcr-abl proteins, in vivo labeling followed by subcellular fractionation was performed. Both normal bcr proteins and the p210 bcr-abl protein were recovered from the cytosolic fraction with little detectable amounts present in other fractions. In vivo labeling was also used to demonstrate that both normal bcr products and the p210 bcr-abl had a relatively long half-life. It is concluded that bcr-abl products, like normal bcr products are located in the cytosolic fraction. PMID- 2232884 TI - Comparison of outcome, clinical, laboratory, and immunological features in 164 children and adults with T-ALL. The Groupe d'Etude Immunologique des Leucemies. AB - T cell acute lymphoblastic leukemia (T-ALL) is a disease of poor prognosis, usually studied separately in adults or children. Controversial clinical or biological prognostic factors have been reported, and little information is available regarding the frequency and prognostic value of membrane markers identified on blast cells. We report an extensive investigation of the incidence and prognostic value of immunophenotypic, clinical, and laboratory data in T-ALL, performed as a multicenter study in 164 patients. CD7, CD5, and CD2 were the most frequently expressed T cell antigens, and CD2 and CD4 were more frequently observed in children than in adults. MHC class II, CD9, and CD10 were observed in 16, 22, and 21% of the patients, respectively. The male prevalence of T-ALL, and the more frequent presence of a tumoral syndrome in children were confirmed, but mediastinal enlargement and high leukocyte counts were observed in less than half the patients. A poor prognosis was associated with the expression of MHC class II in adults. The presence of a mediastinal mass appeared to be of good prognosis in adults, as well as a leukocyte count lower than 100 x 10(9)/l whatever the age of the patient. PMID- 2232886 TI - P190 BCR/ABL transcript in a case of Philadelphia-positive multiple myeloma. AB - Philadelphia positive multiple myeloma is a very rare event and, so far, no molecular data about the involvement of the BCR and C-ABL genes are available. We report here the case of a 64-year-old woman presenting with a typical multiple myeloma and a complex Philadelphia (Ph) chromosome that we investigated at a molecular level using conventional DNA techniques and the polymerase chain reaction (PCR). No rearrangement was observed within the major breakpoint cluster region (M-BCR) although she was found to have a P190 BCR/ABL hybrid transcript using PCR. As far as we know, this is the first description of a P190-type mRNA in a patient with a chronic lymphoid disorder. Since P190 is almost always associated in man with acute forms of hematological malignancies, this suggests that other factors may play a role in determining the phenotype of the disease. PMID- 2232887 TI - Blastic phase of chronic myeloid leukemia (blCML): a proposal for standardization of diagnostic and response criteria. AB - The selection of optimal treatment among the alternatives that are available is especially difficult in blastic phase of chronic myeloid leukemia (blCML) because of the absence of universally agreed upon criteria for the diagnosis of this phase and the absence of definitions of response. Variable response rates, from less than 10 to greater than 90% have been reported, but the highest response rates, in general, have not been reproducible. The application of strict morphologic, cytogenetic, and molecular biologic studies should provide the means for selection of optimal treatment among the new therapies that will be introduced in the future. PMID- 2232888 TI - Splenectomy in advanced chronic lymphocytic leukemia. AB - Between February 1972 and February 1989, splenectomies were performed in 30 patients with chronic lymphocytic leukemia (CLL) and three with prolymphocytic leukemia (PLL) at our institution. Indications for splenectomy included anemia and/or thrombocytopenia (hypersplenism) in 31 patients and symptomatic splenomegaly in two patients. Median time from the diagnosis of CLL to splenectomy was 25 months. Twenty (87%) of the 23 patients splenectomized for thrombocytopenia with or without anemia had platelet increments of greater than or equal to 50 x 10(9)/liter. Hemoglobin increments of greater than or equal to 3 gm/dl were noted in 12 (71%) of 17 patients splenectomized for anemia with or without thrombocytopenia. The median duration of platelet response was 18 months for 19 evaluable patients, and the median duration of hemoglobin response was 62 months for 10 evaluable patients. Median survival time from splenectomy was 36 months. Median survival from diagnosis was 103 months for 10 patients with stage III or IV disease at diagnosis and 79 months for 10 patients with stage II. A prospective study of the effect of splenectomy in a larger number of patients with advanced CLL should be considered. PMID- 2232889 TI - Concordant changes of pyrimidine metabolism in blasts of two cases of acute myeloid leukemia after repeated treatment with ara-C in vivo. AB - Though data from cell lines are abundant, the reason for the development of resistance to 1-beta-D arabinofuranosylcytosine (ara-C) in vivo remains unresolved. A broad interpatient variation of metabolic parameters has further complicated interpretation of the results. The present study compares ara-C metabolism in leukemic blasts of two patients with newly diagnosed disease, before and after repeated treatment with ara-C containing chemotherapy regimens in vivo. Membrane transport of ara-C was unchanged after treatment. In addition, cell-free extracts of blasts obtained after treatment failure showed an unchanged cytidine deaminase activity. Though deoxycytidine kinase activity in cell extracts was unaltered or increased after treatment failure, the activity in situ, measured as the rate of 1-beta-D-arabinofuranosylcytosine triphosphate (ara CTP) formation, was decreased. This could be shown to be due to an expansion of the deoxycytidine triphosphate (dCTP) pool. The severalfold increase in dCTP pool was accompanied by a decrease in thymidine triphosphate (dTTP) pool and correlated with a decrease in deoxycytidylate deaminase (dCMP-deaminase) activity in cell free extracts. Low dCMP-deaminase activity had been shown to confer an ara-C resistant phenotype to cell lines in vitro. Data presented in this paper show that a selection for leukemic blasts with low dCMP-deaminase activity can also be favored by ara-C containing treatment regimens in vivo. Our data suggest that this mechanism might contribute to treatment failure. PMID- 2232890 TI - Chronic myelomonocytic leukemia. AB - Thirty adult patients with CMML were evaluated to determine prognostic factors that might have an impact on conversion to acute leukemia and survival. Neither leukocyte count nor monocyte count correlated with survival. The median survival for all 30 cases was 41 months. Patients with less than 5% marrow blasts had a median survival of 60 months but those with 5-20% blasts had only a 9-month median survival. PMID- 2232891 TI - In vitro studies of erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes. AB - Erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring the in vitro response of primitive (BFU-E) and relatively mature (CFU-E) erythroid progenitors from 12 patients and from eight healthy donors to recombinant human erythropoietin (rhEPO), and by quantifying relationships between circulating EPO levels and progenitor cell frequencies in MDS marrow. Half-maximal growth of MDS CFU-E and BFU-E was detected at a 4-fold higher rhEPO concentration than required by control erythroid progenitors. Nine of the patients evaluated exhibited maximal growth of erythroid colonies at 5- to 20-fold higher than control saturating rhEPO concentrations. Circulating EPO levels in MDS patients were elevated, with a mean value approximately 35-fold higher than that of controls. The frequency of MDS marrow CFU-E and BFU-E was 57 +/- 42% and 18 +/- 9% of the mean control values, respectively. Correlation analysis of the relationships between MDS EPO levels and erythroid progenitors indicated that the anemia in MDS is not attributable to an abnormality in the capacity of EPO to induce the generation of CFU-E, but may be influenced by the BFU-E population, whose severe deficiency results in insufficient influx of EPO-responsive cells. Our findings therefore suggest that treatment of MDS patients with rhEPO may be of limited benefit, since the generation of BFU-E from more primitive ancestors and the initial growth requirements of these cells are not under the regulatory influence of this hormone. PMID- 2232892 TI - Trisomy/tetrasomy 13 in seven cases of acute leukemia. AB - We report the clinical presentation and the morphologic, histochemical, and immunophenotypic characteristics of seven patients with acute leukemia who had trisomy/tetrasomy 13 as the sole cytogenetic abnormality in their leukemia. Five patients had trisomy 13 at diagnosis of acute leukemia. All five of these patients had undifferentiated leukemias. The sixth patient, who had French American-British (FAB) type M2 acute nonlymphocytic leukemia (ANLL), and the seventh patient with biphenotypic acute leukemia developed the trisomic clone as a new abnormality late in the course of their disease. A review of the literature revealed 28 previously reported hematologic malignancies with trisomy 13 or tetrasomy 13q as a solitary cytogenetic abnormality. Trisomy 13 appears to represent another rare but nonrandom cytogenetic abnormality in acute leukemia. In our series trisomy 13 is largely associated with acute leukemia with little myeloid or lymphoid differentiation. PMID- 2232894 TI - Mayo Alumni Association Anniversary. PMID- 2232893 TI - Rationales for a pharmacologically optimized treatment of acute nonlymphocytic leukemia with cytosine arabinoside. PMID- 2232895 TI - Parathyroid hormone-related peptide in lactation and in umbilical cord blood. AB - Parathyroid hormone-related peptide (PTHrP) is expressed in lactating rat mammary glands after suckling, as a result of increases in prolactin rather than suckling per se. In addition, PTHrP produced in the fetal parathyroid glands and placenta may be responsible for stimulation of placental calcium transport. In the current study, we used a radioimmunoassay for human PTHrP to measure levels of the peptide in (1) human breast milk, cow's milk, and two infant formulas; (2) sequential plasma samples in prepartum and postpartum lactating women; (3) women with pathologic hyperprolactinemia; and (4) human umbilical cord blood. In normal subjects, plasma PTHrP levels ranged from less than 2 to 5 pmol/liter. In contrast, human breast milk contained substantially increased levels of immunoreactive PTHrP. Similar elevations were found in cow's milk and in one infant formula. Column chromatography of breast milk demonstrated that PTHrP immunoreactivity included a region of adenylate cyclase stimulating activity, consistent with the presence of biologically active PTHrP. Plasma prepartum PTHrP values did not differ from corresponding postpartum values in lactating women. Women with hyperprolactinemia had a mean plasma PTHrP value in the high-normal range. Umbilical cord blood had considerably suppressed parathyroid hormone values but PTHrP levels that were indistinguishable from those in normal human plasma. Thus, PTHrP is present in high concentrations in breast milk but apparently does not gain access to the maternal circulation in significant amounts. In addition, women with pathologic hyperprolactinemia seem not to have increased levels of circulating PTHrP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232896 TI - Diagnosis of malignant cardiac disease by endomyocardial biopsy. AB - Among oncology patients, endomyocardial biopsy has been used primarily for the evaluation of anthracycline cardiotoxicity. In addition, however, endomyocardial biopsy may be useful for the detection of malignant cardiac neoplasms. Between 1982 and 1989, metastatic involvement of the heart was diagnosed by endomyocardial biopsy in seven patients at our institution. All except one of these patients were older than 50 years of age and had dyspnea as an initial symptom, and all had a known malignant lesion. Results of endomyocardial biopsy confirmed cardiac involvement by a hematologic malignant lesion in four patients and metastatic melanoma in two patients. In one patient, who had a history of breast cancer and lymphoma, a metastatic neoplasm of uncertain differentiation was observed. Myocyte damage was evident in endomyocardial biopsy specimens from two of the four patients with hematologic malignant disease. Endomyocardial biopsy was performed to confirm the possibility of metastatic involvement in five patients; in the other two, endomyocardial biopsy was performed to determine whether anthracycline cardiotoxicity was present, and metastatic involvement was unanticipated. PMID- 2232897 TI - Paraneoplastic cerebellar degeneration: a clinical comparison of patients with and without Purkinje cell cytoplasmic antibodies. AB - In a review of 32 patients with paraneoplastic cerebellar degeneration (PCD), 16 (all of whom were women) had Purkinje cell cytoplasmic antibodies (PCAb) and 16 (8 women) did not. Most patients (15 of 16 seropositive and 12 of 16 seronegative patients) had active cancer at the time of neurologic diagnosis. Gynecologic or breast cancers were found in 14 of 16 seropositive and in 2 of 8 seronegative female patients; lung cancer was diagnosed in 7 of 16 seronegative patients but in no seropositive patient. In seropositive patients, the onset of the syndrome was more often abrupt and abnormalities of affect, mentation, ocular motility, and cerebrospinal fluid IgG index were more common than in seronegative patients. Additional paraneoplastic neurologic syndromes were present in five seronegative patients but in no seropositive patient. Clinical impairment was equivalent in both groups; approximately 75% of patients were confined to a wheelchair or bed at last follow-up. Four of 16 seropositive patients died (4 to 18 months after onset of PCD), and 7 of 16 seronegative patients died (7 to 120 months after onset of PCD). Thus, PCAb seem to be a marker for a clinical subset of female patients with gynecologic or breast cancer. The high frequency of other autoimmune paraneoplastic syndromes in patients with seronegative PCD suggests that PCD in both seropositive and seronegative patients may have a common pathogenic basis that involves an as yet unidentified antineuronal autoimmune mechanism. PMID- 2232898 TI - The mechanism of blood flow during closed chest cardiac massage in humans: transesophageal echocardiographic observations. AB - Despite years of research, the mechanism of forward blood flow during closed chest cardiac massage remains controversial. Two theories have been suggested: the cardiac pump theory and the thoracic pump theory. Transesophageal echocardiography offers a new approach for study of the flows and cardiac morphologic features during chest compressions in humans. Case reports are presented to illustrate the use of transesophageal echocardiography during cardiopulmonary resuscitation. The findings included right and left ventricular compression, closure of the mitral valve during compression, opening of the mitral valve during the release phase, and atrioventricular valvular regurgitation during compression, indicating a positive ventricular-to-atrial pressure gradient. These findings suggest that direct cardiac compression was the predominant mechanism of forward blood flow during cardiopulmonary resuscitation in these patients. An understanding of the actual mechanisms involved is necessary if improved cardiopulmonary resuscitative techniques or adjuncts are to be rationally developed for enhancing the outcome of resuscitation. PMID- 2232899 TI - Endothelin: a new cardiovascular regulatory peptide. AB - Endothelin, a recently discovered peptide produced by endothelial cells, contracts vascular strips in vitro with greater potency than any previously known vasoconstrictor. Infusions of pharmacologic doses of endothelin in vivo result in a prolonged pressor response and a preferential impairment of renal hemodynamic and excretory functions. Endothelin also directly stimulates the release of aldosterone from the adrenal gland and inhibits renin release in vitro. A highly sensitive and specific radioimmunoassay has confirmed that endothelin circulates in human plasma, and increased plasma endothelin levels have been associated with various cardiovascular disease states. This review summarizes the current knowledge about the molecular biologic features and physiologic actions of endothelin and also explores the role of endothelin, through its local and systemic function, as a regulator of vascular tone in normal and pathophysiologic states. PMID- 2232900 TI - Assessment of functional gastrointestinal disease: the bowel disease questionnaire. AB - A need exists for a self-report questionnaire that reliably and accurately measures symptoms and that distinguishes patients with functional gastrointestinal disease from those with other conditions. We have developed such an instrument, the bowel disease questionnaire, and herein describe details of its discriminatory validity. Data from 399 subjects were analyzed. Patients with gastrointestinal symptoms were ultimately diagnosed as having functional gastrointestinal disease (82 with the irritable bowel syndrome and 33 with functional dyspepsia) or organic gastrointestinal disease (N = 101). There were 145 healthy control subjects and 38 patients with a psychiatric disease, somatoform disorder (which includes those with a diagnosis of hypochrondriasis, psychogenic pain, and somatization or conversion disorder). All subjects completed the questionnaire before undergoing an independent diagnostic assessment by experienced physicians. Functional gastrointestinal disease could be distinguished from organic disease, somatoform disorder, and health by using models derived from logistic discriminant analysis. With use of these models, the estimated probability of functional gastrointestinal disease was then calculated. Descriptive symptom scores were of less value than the scores derived from the data sets by logistic discriminant analysis. Age did not significantly affect the responses to the questionnaire items. We conclude that, in the population studied, the bowel disease questionnaire is a valid measure of symptoms of functional gastrointestinal disease, and this instrument may have clinical and research applications. PMID- 2232901 TI - Polymyositis: a case history approach to the differential diagnosis and treatment. AB - A wide range of conditions can mimic polymyositis. Thus, diagnosing this condition can be a challenge. Although no single criterion is diagnostic of polymyositis, the following criteria have been proposed and widely used: (1) symmetric proximal muscle weakness; (2) characteristic violaceous rash on the hands, elbows, and knees; (3) increased muscle enzymes in the serum; (4) characteristic electromyographic findings (insertional activity, fibrillation potentials, motor unit potentials of increased frequency and decreased duration, and normal conduction velocity in nerves); and (5) muscle biopsy specimen with characteristic inflammatory and myopathic changes. Although polymyositis primarily involves muscle, up to 20% of patients may have extramuscular problems. The main treatment for polymyositis is high-dose corticosteroids. In corticosteroid-resistant patients, methotrexate is often effective. In this report, case histories are presented to highlight the usefulness and the limitations of the common diagnostic criteria for polymyositis. PMID- 2232902 TI - Renal cell carcinoma associated with sarcoidlike tissue reaction. AB - A 60-year-old man was referred to our institution with the diagnosis of sarcoidosis. Because of several months' complaint of right flank pain and weight loss, the patient had consulted his local physician. After an extensive workup revealed only cholelithiasis, he underwent a cholecystectomy for presumed chronic cholecystitis. At the time of operation, biopsy of several liver nodules and peripancreatic nodes revealed noncaseating granulomas, consistent with sarcoidosis. On initial examination at our institution, the patient had microhematuria. A chest roentgenogram demonstrated multiple pulmonary nodules, an abdominal computed tomographic scan showed an indeterminate left renal mass, and magnetic resonance imaging of the spine revealed abnormal signals in the body of T-12. Open-lung biopsy showed an adenocarcinoma with clear cell features, likely of renal origin. The patient was diagnosed as having a metastatic renal carcinoma associated with a sarcoidlike tissue reaction. Although noncaseating granulomas have been reported in association with other malignant lesions, to our knowledge this is the first report of such an association with renal carcinoma. In addition, this case illustrates several points. First, sarcoidosis is a multisystem disorder with protean extrapulmonary manifestations. In fact, all our patient's findings could have been attributed to sarcoidosis. Second, noncaseating granulomas occur with many types of processes, including infections, chemical exposures, and, as in this case, neoplasms. Thus, noncaseating granulomas are not pathognomonic for sarcoidosis. Third, sarcoidosis is a clinical diagnosis that cannot be based on histologic findings alone. PMID- 2232903 TI - Parathyroid hormone-related protein. PMID- 2232904 TI - The endomyocardial biopsy revisited. PMID- 2232905 TI - Medical symbols: the staff of Aesculapius. PMID- 2232906 TI - Accessory molecules and antigen requirements for young and aging cytotoxic lymphocytes. AB - In this study I have investigated whether young and aging alloreactive cytotoxic T-lymphocytes (CTL) have comparable antigen requirements, and whether the accessory molecules Ly2 and LFA-1 participate similarly in cytolysis mediated by young and old cells. Spleen and lymph node cells from young and aging, naive and primed mice were stimulated in bulk culture with allogeneic cells; cytotoxicity and proliferation were then measured. Additionally, lymph node cells were cultured under limiting dilution conditions, and the resultant clones here tested for cytotoxicity in the presence or absence of antibodies against Ly2 and LFA-1. I found that accessory molecules from naive and primed, young and aging splenic CTL participated similarly in cytolysis. However, both cytotoxic and proliferating splenic T-cells from aging mice required a greater alloantigen concentration for optimal response. Heterogeneous lymph node CTL from old mice demonstrated less cytotoxicity than young CTL, and, on the clonal level, old naive CTL clones were less active than young clones. Naive aging clones were more resistant than young clones to anti-Ly2 and anti-LFA-1. After priming, clone activity among the various age groups did not differ. These results suggest a qualitative difference between young and old cytolytic cells prior to alloantigen priming in vivo. PMID- 2232908 TI - Age-related changes in the cholinergic components within the central nervous system. II. Working memory impairment and its relation to hippocampal muscarinic receptors. AB - Cognitive performance in aging Wistar rats was monitored using the radial arm maze and the latter was correlated with the density of muscarinic receptors in the CNS, using quantitative in vitro receptor autoradiography. Significant working memory deficits were observed in 12, 17 and 24-month-old rats as compared to 3-month-old animals. In addition, the number of the muscarinic receptors declined significantly with age (from 27 to 42% depending on the brain region sampled) utilising [3H]QNB and [3H]PZ receptor binding assays. The above trend became evident already at the age of 12 months. The present findings support the association of central cholinergic activity with memory processes. PMID- 2232907 TI - Protein carboxyl methylation and methyl ester turnover in density-fractionated human erythrocytes. AB - A widely distributed methyltransferase modifies protein D-aspartyl and L isoaspartyl residues which arise spontaneously as proteins age. Protein carboxyl methylation reactions were analyzed in human erythrocytes which had been separated on density gradients, a procedure which provides fractions enriched in older cells in the denser areas of the gradient. The total flux of methyl groups through the carboxyl methylation pathway was monitored by incubating cells from each fraction with L-[methyl-3H]methionine and measuring the formation of both protein [3H]methyl esters and [3H]methanol, derived from the hydrolysis of protein [3H]methyl esters in vivo. Cells isolated from denser areas of the gradient showed progressively higher rates of both protein carboxyl methylation and methanol production. In all cases, only 10-20% of the total methyl groups transferred were still present as intact protein [3H]methyl esters, consistent with the rapid hydrolysis of protein methyl esters in erythrocytes of all ages. The total flux of methyl groups through the carboxyl methylation pathway was approximately 3-fold higher in cells isolated from densest areas of the gradient compared to cells isolated from least dense areas of the gradient. Increases of a similar magnitude were observed in the numbers of both membrane protein carboxyl methyl esters and cytosolic protein carboxyl methyl esters. The only protein whose methylation was unchanged in denser cells was a 35,000 Da cytosolic protein. It has been proposed that protein carboxyl methyl esters are intermediates in either the repair or metabolism of structurally damaged proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2232909 TI - Cholesterol accumulation in plasma membrane and changes of membrane enzyme activity of Acholeplasma laidlawii cells during culture ageing. AB - The data presented in this report show that the microviscosity of the plasma membrane and the cholesterol/phospholipid molar ratio of its lipid bilayer increases during ageing of Acholeplasma laidawii cultures. At the same time the age changes of other lipid components content do not correlate with the change of membrane viscosity. It is also shown that membrane enzyme activities of mycoplasma cell decrease with age. These results confirm the membrane hypothesis of ageing according to which increased microviscosity is the essential factor of cell ageing. PMID- 2232910 TI - Ascorbic acid uptake by young and aged guinea pig lenses. AB - The dynamics of in vitro uptake of [14C]-ascorbic acid into intact lenses of young (50 days old) and old (730 days old) guinea pigs was evaluated in this study. Two-dimensional protein gel analysis of [35S]-methionine labeled proteins provided evidence that the isolated lenses were viable throughout the culture period. It was found that the in vitro uptake of ascorbate into these lenses follows similar saturation kinetics for lenses from both age groups. Moreover, the linear uptake rate was identical. Ascorbate transport was inhibited by phloretin, p-chloromercuribenzoate, insulin, glucose and ouabain; however, no inhibition was observed with 2,4-dinitrophenol or NaF. These results suggest that the lenticular ascorbate concentration is regulated by a facilitated diffusion process and it not energy-dependent. Data on ascorbate transport into lenses from aged guinea pigs provide strong evidence that the abnormally low ascorbic acid concentrations in lenses of old mammals is not likely the result of a decreased lenticular uptake ability. PMID- 2232911 TI - Hepatic cytosolic glutathione S-transferase activities in ageing brown Norway rats--importance of sex differences and phenobarbital treatment for studies of ageing. AB - Age-associated alterations of hepatic cytosolic glutathione S-transferase activities towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene were investigated in Brown Norway rats of both sexes (11-144 weeks old), under control conditions and after administration of phenobarbital. With both substrates, small changes in glutathione S-transferase activities are observed for the control rats (15-53 weeks old). For these specific age groups, male glutathione S-transferase activities are significantly higher than those of their female counterparts, with sex-related differences being most pronounced after 1,2 dichloro-4-nitrobenzene conjugation. Using 1-chloro-2,4-dinitrobenzene as a 'general' substrate, the sex-differences tend to decrease from the age of 53 weeks onwards to become non-significant at the age of 112 weeks. Phenobarbital administration significantly increases the total and the isoenzymes 3-3 and 3-4 activities in both sexes, with the highest and the lowest increase being observed in the youngest and oldest animals, respectively. It therefore can be concluded that some age-related variations exist as far as the glutathione S-transferase activity of both control and phenobarbital-treated rats are concerned, but that the changes observed are rather small. On the contrary, the parameters 'Sex' and 'Phenobarbital treatment' are found to be responsible for the major activity changes observed. PMID- 2232912 TI - Influences of physical training on the functional changes of young and old red blood cells. AB - Eleven male elite endurance-trained athletes and 10 male elite strength-trained athletes were compared to a non-trained group of men, to determine the effect of training on some haematological parameters and some indicators of red cell membrane properties. Erythrocytes were age-fractionated by centrifugation in Percoll gradients. It has been found that in the reticulocytes and young erythrocytes of endurance trained athletes activity of acetylcholinesterase (AChE) and concentration of glutathione (GSH) were higher than in strength trained athletes and control. The red cell osmotic fragility (RCOF) and glycerol lysis time (GLT) of young cells were similar in all investigated groups. The endurance training indicating chronic adaptation mechanisms in significant changes of red cell metabolism but non membrane properties. PMID- 2232913 TI - Longitudinal Gompertzian analysis of amyotrophic lateral sclerosis mortality in the U.S., 1977-1986: evidence for an inherently susceptible population subset. AB - Age-adjusted mortality rates for amyotrophic lateral sclerosis (ALS) for men and women in the United States from 1977 to 1986 were determined and subjected to longitudinal Gompertzian analysis. The exponential decline in the rate of increase of age-adjusted ALS mortality rates after age 55 years is most consistent with the existence of an inherently susceptible population subset that is decreasing faster than the general population. In the U.S. between 1977 and 1986, annual age-adjusted ALS mortality rate distributions were determined by a common fixed intersect point (for men, the death rate at age 46.38 years was 0.91/100,000; for women, the death rate at age 45.85 years was 0.46/100,000); and an environmental factor that varied erratically during the decade by a factor of 7.21 for men and 11.64 for women. On the average, the U.S. environment during this period was 4.33 times more conducive to mortality from ALS in men than in women. Overall ALS mortality between 1977 and 1986 increased 46% and 49% for men and women, respectively. The common fixed intersect point in mortality rate distributions suggests that these increases were real and not merely the result of improved diagnosis and/or better reporting. The overall increase in ALS mortality most likely results from an effective increase in the susceptible population subset due to increasing life expectancy, rather than to environmental factors. That is, as life expectancy increases, more of the susceptible population subset live long enough to express the disease. PMID- 2232914 TI - Longitudinal Gompertzian analysis of Parkinson's disease mortality in the U.S., 1955-1986: the dramatic increase in overall mortality since 1980 is the natural consequence of deterministic mortality dynamics. AB - Age-adjusted mortality rates for Parkinson's disease (PD) for men and women in the United States, from 1955 to 1986, were calculated and subjected to longitudinal Gompertzian analysis. Annual age-adjusted PD mortality rate distributions were determined by a common intersect point and a variable environmental factor. For men, the death rate at age 73.75 years was 19.15/100,000; for women, the death rate at age 78.99 years was 28.64/100,000 for each year from 1955 to 1986. The environmental factor declined (improved) 360.7 fold for men and 319.6-fold for women in 1986 compared to 1955. Despite this dramatic environmental improvement favoring survival in PD, there has been a 57.6% increase since 1980 in the annual crude PD mortality rate for men compared to the stable annual crude mortality rate from 1955 to 1979. A corresponding 37.9% increase in the annual crude PD mortality rate for women has also occurred since 1980. The increase in overall mortality is due entirely to rapidly increasing age-adjusted mortality rates at ages greater than the intersect points for men and women. The results suggest that overall mortality due to common 'degenerative' diseases may increase dramatically as has occurred in PD. PMID- 2232915 TI - Longitudinal Gompertzian analysis of stroke mortality in the U.S., 1951-1986: declining stroke mortality is the natural consequence of competitive deterministic mortality dynamics. AB - Age-adjusted mortality rates for stroke in the United States from 1951 to 1986 were subjected to longitudinal Gompertzian analysis. Age-adjusted stroke mortality rate distributions were determined by a variable environmental factor and a constant Gompertz slope. Compared to 1951 values, the environmental factor in 1986 had declined (improved) 49.8% for men and 59.1% for women. This was associated with a 51.9% and 31.4% decrease in the annual crude mortality rate from stroke for men and women respectively. However, the Gompertz slope remained remarkably constant from 1951 to 1986; 0.050152 for men and 0.048341 for women. The constant Gompertz slope for age-adjusted mortality rate distributions for stroke is in sharp contrast to the increasing Gompertz slope which occurs with an improving environment in 'degenerative' diseases and aging in general. These findings suggest that the recent dramatic decline in overall stroke mortality is the natural consequence of competitive deterministic mortality dynamics. As the overall environment becomes more conducive to human survival, Gompertzian diseases with converging mortality rate distributions must increase as causes of human mortality at the expense of diseases with constant Gompertz slopes. PMID- 2232916 TI - Tumor necrosis factor reduces lifespan of human endothelial cells in vitro. AB - Tumor necrosis factor (TNF) is known to regulate the proliferation and function of vascular endothelial cells (ECs). We have examined the effects of TNF on the growth and aging of human ECs of different origins and compared them with those in human normal diploid fibroblasts. The results obtained were as follows: (1) TNF reduces the growth rate and in vitro life span of ECs in both dose- and treatment length-dependent fashions; (2) ECs are significantly more sensitive to TNF than fibroblasts; and (3) the life span shortening effect of TNF on ECs increases as a function of in vitro cell age. These results suggest that the aging of ECs is modified by TNF exposure. PMID- 2232917 TI - Periodic clustering of human disease-specific mortality distributions by shape and time position, and a new integer-based law of mortality. AB - Human mortality distributions were analyzed for 29 disease-specific causes-of death in male and female, White (U.S.A.), Black (U.S.A.) and Japanese (Japan) populations, constituting a total of 162 separate cohorts. For each cohort distribution, the curve moments and the parameter values for fits to model equations were determined. The differences between cohort distributions were characterized by two degrees of freedom, related to distribution position and shape, respectively. A form of the Weibull function was shown to contain two parameters that mapped to these two degrees of freedom. Parametric analysis on 136 best-fitting cohorts yielded periodic clustering in the set of values for both Weibull parameters as quantitated using a Fourier transform method and an independent statistical method. This periodicity was unlikely to have occurred by chance (P less than 0.01). We have combined these results into a Law of Mortality, based on a Weibull function containing only integer parameters and constants, which is valid for all human age-related disease mortality. We show that the life expectancy differences between races and sexes is completely described by this formalism. We conclude that human mortality is controlled by discrete events, which are manifested in the appearance of only allowed mortality curve shapes and positions. PMID- 2232918 TI - Administrative data and outcomes research. PMID- 2232919 TI - The effects of monitoring and feedback on compliance. AB - A two-group randomized experimental design was employed to assess the effects of monitoring and feedback on the compliance of 93 psychiatric outpatients treated with lithium. Compliance in both groups was measured using self-report, lithium level, appointment-keeping, and medication refill frequency. The experimental group was also monitored using a unique electronic device that records the time and day pills are removed. At the midpoint of the study, the experimental group received feedback about serum lithium levels and patterns of removing medications from the monitoring device while the control group received feedback about serum lithium levels only. The study demonstrated no sustained effect of the monitoring and feedback interventions on compliance. PMID- 2232920 TI - Services and charges by PPO physicians for PPO and indemnity patients. An episode of care comparison. AB - Physicians who participate in preferred provider organizations (PPOs) usually agree to various types of utilization review and sometimes discount their charges or agree to accept lower fees. This study was performed to determine whether they provided more or fewer services to their PPO patients than to their indemnity patients and whether the discounting resulted in lower expenditures for each episode of illness. In 1984, Metropolitan Life offered PPO coverage to Dade County (Florida) school board employees and dependents but only a standard indemnity plan to Dade County government employees and dependents. Episodes of care were examined for patients with chest pain, hypertension, joint pain, gastrointestinal or liver disorders, and lower back pain cared for by physicians who treated patients in both the PPO and indemnity employee groups. For PPO patients, charges per physician service were the same or lower, but total physician charges during an episode were higher. For services such as laboratory tests, diagnostic x-rays, and room and board, PPO and indemnity patients' charges were not significantly different. PMID- 2232921 TI - The effect of drug co-payments on utilization and cost of pharmaceuticals in a health maintenance organization. AB - This study analyzed how the use and cost of pharmaceuticals varied by level of drug co-payment in a staff model health maintenance organization (HMO). An historical cohort design was used to study changes in drug utilization and drug costs in 19,982 continuously enrolled beneficiaries less than the age of 65. The beneficiaries initially had no drug co-payments, but experienced co-payment rates of $1.50, $3.00, and $3.00 plus other benefit changes during a three-year period. A comparison cohort of 23,164 beneficiaries was selected from the same setting who were subject to no drug co-payment during the same time period. Data on the use and cost of medications were obtained from an automated data system. Adjusted analyses for each time period controlled for age, sex, years in the Group Health Cooperative (GHC), and prior year utilization (or cost). The initial $1.50 drug co-payment was associated with a drop of 10.7% in the number of prescriptions filled relative to change in the comparison cohort. The decrease was greatest for discretionary drugs at each level of co-payment. The implementation of progressively greater levels of co-payments continued to have a significant effect on drug utilization since each co-payment level resulted in an additional reduction in drug utilization; 10.6% with the $3 co-payment and 12.0% when the $3 drug co-payment was combined with other cost-sharing provisions. Co-payments were associated with lower per capita drug costs and higher per prescription unit costs. PMID- 2232922 TI - HMO enrollment by Medicare beneficiaries in heterogeneous communities. AB - This study examines the effect of ethnicity, race, and other socioeconomic and utilization variables on belonging to a fee-for-service or capitated plan by Medicare beneficiaries. Native-born beneficiaries cite health status, physical access to health care facilities, and income levels as affecting their choice. Immigrants, on the other hand, mention age, a lifestyle of living alone, and income as influencing their decision. Among foreign-born nationals, race appears to play an important role in choosing health care plans. A key factor affecting enrollment among immigrant populations appears to be the availability of ethnic sensitive providers of health care. While the elderly Hispanic immigrant population utilizes participating providers in prepaid plans catering to a Spanish-speaking population, the lack of similar facilities among predominantly black immigrant neighborhoods inhibits participation in HMOs by elderly immigrants from places such as Haiti and the Caribbean Basin. Policy implications are discussed. PMID- 2232923 TI - Drug formularies: myths-in-formation. AB - Drug formularies are pivotal tools for delineating and directing prescribing to the "drugs of choice." Full realization of their potential has been hampered by insufficient comparative data on drug efficacy/safety and local resources for formulary development. However, misconceptions concerning fundamental formulary concepts pose an even more formidable obstacle. This article identifies statements illustrating formulary misconception a) made by physicians attending Pharmacy and Therapeutics Committee meetings during a three-year period and b) appearing in published sources. The paper highlights basic objectives and operational requirements of an effective formulary, and contrasts this definition with 20 myths and misinformation culled from these two sources. Not only does such misinformation impair formulary development, many critics are so preoccupied with alleged shortcomings that progress in minimizing the real limitations of formularies has been impeded. PMID- 2232924 TI - A proposed new system for valuing dental procedures. The relative time-cost unit. AB - The relative time cost unit (RTCU) is a proposed new system for valuing dental procedures that provides an alternative to traditional relative value units in fee-setting and reimbursement allowances. It incorporates personnel costs, task mixes, and task times into relative weights for dental procedures. The frequently performed procedure, "2-surface amalgam restoration," is used to illustrate how the RTCU values are derived from hospital task analysis data. The RTCU, as a data based construct, holds appeal for restructuring fee schedules and has been used for almost a decade by insurance companies to value dental services, construct fee schedules, and evaluate reimbursement to providers. PMID- 2232925 TI - The risk of nursing home use in later life. AB - Data from the 1982-1984 National Long-Term Care Survey were used in this paper to estimate the risk of nursing home use. The data revealed that 37% of a nationally representative sample of individuals dying between 1982 and 1984 used a nursing home sometime after turning 65. This proportion increased with longevity and was higher among females and whites and in the North Central and Western regions of the country. Because individuals now turning 65 have a longer life expectancy than the persons studied, they face an even higher remaining lifetime risk of nursing home use (43%). Assuming that past utilization patterns will continue, over half of the women and almost one-third of the men turning 65 in 1990 can be expected to use a nursing home sometime before they die. PMID- 2232926 TI - Expanding Medicaid drug formulary coverage. Effects on utilization of related services. AB - Effects on utilization and expenditures occurring concurrently with an expansion of coverage in the South Carolina Medicaid drug formulary were investigated. Data were collected for prescriptions, physician office visits, and outpatient and inpatient hospital visits. Data were evaluated for a cohort of 12,139 individuals who had at least one prescription claim and were continuously eligible for benefits during the two-year study. A repeated measures design was employed to control the differences between subjects. A multivariate analysis of variance was used to detect overall differences in utilization and expenditures. A priori comparisons of means were performed to detect changes in levels and rates of expenditures and utilization for each service. Increases were observed in the number of prescriptions, physician visits, and outpatient visits per person while the number of inpatient hospital admissions declined. Similarly, expenditures increased for all service areas except the inpatient hospital service. The proportion of variance explained by the formulary change was small in all service areas, but would be of practical significance because of the large number of Medicaid recipients affected. From a theoretical perspective, an association of a reduction in inpatient hospital use and expenditures following the elimination of drug formulary restrictions is particularly noteworthy. These findings support the thesis that medical care services should not be viewed in isolation but rather as a system of interrelated activities. Interventions in one portion of the system are mirrored by changes in utilization of other components. Frequently, private and public medical care programs are managed with organizationally distinct benefit budgets, which are controlled independently. In view of the results of this study, this organizational approach may lead to a suboptimal allocation of resources. PMID- 2232927 TI - Parent anxiety and satisfaction with a pediatric visit. PMID- 2232928 TI - Using the delay tool to attribute causes for unnecessary pediatric hospital days. PMID- 2232929 TI - Note on controlling risk in capitation payment. Actuaries rate HMOs in a different fashion. PMID- 2232930 TI - Energy imbalance and cancer of the breast, colon and prostate. AB - In Western societies, energy imbalance is characterized by obesity and sedentary life styles and is associated with increased morbidity and mortality from all causes of cancer, including cancer of the breast, colon and prostate. The interrelationships of energy intake and energy retention, to energy expenditure and physical fitness need further investigation from the physiologic, metabolic, endocrine and genetic aspects of cancer development, since obesity, energy expenditure and cancer have a familial predisposition. The effects of exercise on estrogen and prostaglandin metabolism and their relationship to cancer development require further investigation. Although the exact amount and intensity of exercise that confers benefit is not known, physical activity and physical fitness are inversely associated with all-cause mortality, including cancer. These findings have important public health implications, because about one-third of persons in industrialized societies are quite sedentary, and the prevalence of low physical fitness is quite high. The balance between total energy intake and expenditure may be more important in cancer development than the intake of any given dietary component or energy source. Exercise increases prostacyclin and decreases the aggregation of platelets and possibly decreases the platelet derived growth factors (PDGF). One could speculate that exercise may in turn decrease the probability of developing colon cancer in those who are predisposed to it, since the SIS oncogene is in fact a variant of PDGF. PMID- 2232933 TI - Conjugated dienoic derivatives of linoleic acid: a new class of anticarcinogens. AB - Evidence establishing the anticarcinogenic activity of the conjugated dienoic derivatives of linoleic acid (CLA) is reviewed. Our findings demonstrate that CLA is a potent antioxidant and that the c-9,t-11 CLA isomer is selectively incorporated into cellular phospholipid, which may at least in part explain the anticarcinogenic activity of CLA. Dietary sources of CLA include grilled beef, cheese, and related foods. Another source of CLA is its endogenous generation via the carbon centered free radical oxidation of linoleic acid. We propose that the formation and action of CLA represents a previously unrecognized in situ defense mechanism against membrane attack by oxygen radicals. PMID- 2232932 TI - Short-term tests and long-term prospects for colon cancer prevention. AB - Five assay systems that have been used for identifying possible carcinogenic factors responsible for human colon cancer are described. These are: Salmonella, colonic micronuclei, colonic epithelial proliferation and aberrant crypt assays, and polyp recurrence trials. The assays have led to the development and testing of 7 hypotheses. A review of this process points to the importance of specificity in the assay system. PMID- 2232931 TI - Dietary prevention of breast cancer. AB - A review of the epidemiological and experimental data suggests that dietary modification does have a place in breast cancer prevention. This needs to be considered at three levels: dietary recommendations for the general population, dietary intervention in the management of women at high risk for breast cancer, and the place for dietary therapy as a component of regimens intended to reduce risk of recurrence after primary treatment of breast cancer ('secondary prevention'). Based on present evidence, a dietary approach to breast cancer prevention should include weight control, when indicated, a reduction in dietary fat intake to approximately 20% of total fats, and an increase in fiber consumption to 25-30 g day-1. Further studies are indicated to determine the optimal qualitative composition of dietary fat consumed, and the nature of supplemental fiber. PMID- 2232934 TI - The importance of N-6 and N-3 fatty acids in carcinogenesis. AB - Cross-cultural comparisons show that total fat intake is related to breast and colon cancer mortality. Total fat consists of different fatty acid families. Therefore different fatty acids should be studied in relation to breast and colon carcinogenesis. Animal experiments suggest that N-6 polyunsaturated fatty acids may have a tumor promoting effect and that N-3 polyunsaturated fatty acids may exert an inhibitory effect on chemically-induced mammary and colon tumorigenesis. Data from epidemiologic studies in this area are scarce. Comparisons between Japan and Iceland and between Eskimos and Danes suggest that a low-fat diet in combination with a N-3/N-6 polyunsaturated fatty acid ratio of about 0.5 seems to be associated with low mortality rates from breast and colon cancer. Much more research is needed to determine the optimal intake of total fat, N-6 and N-3 polyunsaturated fatty acids in relation to breast and colon cancer prevention. PMID- 2232936 TI - Mineral insufficiency and cancer. AB - There are excellent theoretical reasons why the mineral nutrients selenium, manganese, copper and zinc, known as the antioxidant minerals, may be involved in the prevention of cancer aetiogenesis. The biochemistry is discussed of the part played by the antioxidant minerals, in the wider context of the other dietary antioxidants vitamins A, E and C, and beta carotene, in preventing tissue damage caused by activated metabolites of oxygen. The likely part played by these oxygen metabolites is described and a detailed review given of the evidence that suggests a role for antioxidant minerals, notably selenium, in preventing carcinogenesis in a range of animal models. There follows a summary of the emerging epidemiological evidence that suggests clearly that low selenium intake is a risk factor in the aetiology of human cancer. PMID- 2232937 TI - Strategies for cancer prevention through diet modification. AB - Diet and cancer research at the National Cancer Institute has grown from a budget of $2.5 million in 1974 to $55 million in 1988. The emphasis is partially on demonstrations of prevention strategies and chemoprevention trials. Studies to disseminate dietary goals in practical ways are undertaken with the aid of the food industry. PMID- 2232935 TI - Experimental approaches to nutrition and cancer: fats, calories, vitamins and minerals. AB - Chronic energy intake restriction (CEIR) inhibits lymphoproliferative disease, autoimmune-based renal disease and mammary adenocarcinoma in mice of numerous short-lived strains (MRL/lpr, C3H/Bi, C3H/Ou). Doubling and tripling of life span and health span and inhibition of development of diseases associated with aging could be attributed to restriction of calories but not to restriction of dietary fat in the absence of calorie restriction. In mice of both long- and short-lived strains, CEIR dramatically prevents the waning of immunologic vigor that commonly occurs with aging, delays thymic involution, impairs formation of circulating immune complexes, prevents the renal injury that accompanies autoimmune disease, and significantly forestalls development of genetically determined lymphoproliferative or neoplastic disease. Evidence suggests that CEIR may exert these beneficial influences in part through regulation of cellular proliferation. Trace elements, particularly zinc, as well as vitamins may play important roles in maintaining immunocompetence and also appear to be of significance in the dietary prevention of certain experimental cancers. PMID- 2232939 TI - Nutrition and cancer. The fourth international symposium organized by the Hematology Collaborating Group. Stockholm, Sweden, 21-22 September 1989. Proceedings. PMID- 2232938 TI - Nutritional intervention studies in cancer prevention. AB - Nutritional intervention trials are important tools in the search for efficient cancer prevention strategies. They can be divided into two types of trials; chemoprevention in which intervention is a defined chemical agent or a micronutrient, and diet trials in which intervention is a change in dietary habits. The most commonly used chemopreventive agents are retinoids, beta carotene, and vitamins. The chemopreventive trials are directed to general cancer prevention or focus on target organs. The diet intervention studies include subjects at increased risk for cancer, cancer patients and community-based intervention programs. Although several completed chemopreventive studies indicate that certain micronutrients can prevent neoplastic growth, the follow-up period is still too short for most nutritional intervention studies to determine whether their preventive strategies are effective. PMID- 2232940 TI - Inducers and scavengers of free radicals in the food. PMID- 2232942 TI - Gastric carcinogenesis: diet as a causative factor. AB - Gastric cancer is a very typical cancer related to life styles, including nutrition and dietary conditions. Cigarette smoking has also been pointed out as an enhancing factor in gastric cancer development. Improvement of dietary conditions, regular dietary habits including lower salt, nitrite and nitrite intake and balanced nutritious food may be factors suppressing the incidence of gastric cancer. At the same time, advances in technology for early diagnosis and early surgical treatment have elevated the cure rate of gastric cancers. From both primary and secondary cancer prevention aspects, gastric cancer is now a conquerable disease. PMID- 2232943 TI - The diet and cancer hypothesis: current trends. AB - The current decade has witnessed an increasing interest in the diet-cancer issue as a central one for public health. Notwithstanding a substantial amount of epidemiological investigations, firm evidence of carcinogenicity exists only for alcoholic beverages with respect to cancers at several sites, and for aflatoxin with respect to liver cancer; also, the relation is established between diet related excess of energy intake, as translated into obesity, and cancer of endometrium and gallbladder. For a number of other dietary factors the evidence for a causal or protective role still remains at a presumptive level (e.g. intake of fresh vegetables and fruits with respect to cancers at several sites), or is still frankly open to debate (e.g. fat with respect to breast and colon cancer). Methodological inadequacies in past studies have been identified and clearer results should derive in the coming decade from epidemiological investigations substantially improved in methodology, particularly from the long-term prospective studies as now planned by the International Agency for Research on Cancer. Fortunately for cancer prevention, such dietary advice as can be derived from the highly incomplete and unsatisfactory knowledge on the role of dietary factors on cancer, turns out to be in broad agreement with the advice aimed at preventing other major diseases such as ischaemic heart disease and hypertension. This allows the issuing of a set of simple but important 'prudent diet' recommendations. PMID- 2232944 TI - [Dexfenfluramine: a new approach in the treatment of overweight]. PMID- 2232945 TI - [Acute myelofibrosis]. PMID- 2232941 TI - Dietary carcinogens, environmental pollution, and cancer: some misconceptions. AB - Various misconceptions about dietary carcinogens, pesticide residues, and cancer causation are discussed. The pesticides in our diet are 99.99% natural, since plants make an enormous variety of toxins against fungi, insects, and animal predators. Although only 50 of these natural pesticides have been tested in animal cancer tests, about half of them are carcinogens. About half of all chemicals tested in animal cancer tests are positive. The proportion of natural pesticides positive in animal tests of clastogenicity is also the same as for synthetic chemicals. It is argued that testing chemicals in animals at the maximum tolerated dose primarily measures chronic cell proliferation, a threshold process. Cell proliferation is mutagenic in several ways, including inducing mitotic recombination, and therefore chronic induction of cell proliferation is a risk factor for cancer. PMID- 2232946 TI - [Pulmonary microvascular cytology in critical patients]. AB - Cytology in blood drawn through a wedged Swan-Ganz catheter appears as a sensitive method for the diagnosis of carcinomatous lymphangitis in patients in whom transbronchial biopsy is considered dangerous or who refuse to undergo the latter procedure. However, its usefulness has not been assessed in critical patients with acute respiratory failure of unknown etiology in whom malignant disease is suspected. We report our experience in two patients admitted to the Intensive Care Unit with acute respiratory failure of unknown etiology: they were a female with breast carcinoma and a male with lymphoma in whom the cytological study of pulmonary capillary blood disclosed malignant cells. The clinical evaluation and the subsequent histological studies confirmed the pulmonary involvement by malignant disease in both cases. PMID- 2232948 TI - [Success with enalapril after captopril-induced neutropenia]. PMID- 2232949 TI - [Mortality statistics and validity of the certification of causes of death in Spain: a necessary specification]. PMID- 2232947 TI - [Drug treatment of male infertility]. PMID- 2232950 TI - [Search, critical selection and citation of bibliographic references in medical articles]. PMID- 2232951 TI - [Tolerance of continuous positive nasal pressure treatment in obstructive sleep apnea syndrome]. PMID- 2232953 TI - Validation and testing of medical decision aids. Introduction. PMID- 2232952 TI - [Infectious endocarditis in drug addicts: a study of 71 cases]. AB - Infective endocarditis (IE) is a severe and relatively common condition in parenteral drug abusers (PDA). Seventy-one IE episodes in 59 PDAs admitted to the Hospital General Vall d'Hebron from August 1978 to December 1988 were evaluated. The disease basically involved young males, with a progressively increasing incidence throughout the decade and a higher frequency during August. Fever was a constant symptom, with a duration of less than 10 days before admission in 73% of cases. Staphylococcus aureus was the most common pathogen (85% of episodes). Vegetations were detected by echocardiography in 70% of cases. In 82% of episodes the right side of the heart was involved, particularly the tricuspid valve. The initial chest X-ray film was abnormal in 57.5% of episodes. In 7 patients features of heart failure were present at admission; most had left heart endocarditis. Three patients with left heart endocarditis required surgical therapy. Overall mortality was 13%; it was 6% in patients with only tricuspid involvement and 27% when the left heart was involved. PMID- 2232954 TI - The evaluation of clinical decision support systems: what is necessary versus what is interesting. AB - The evaluation of clinical decision support systems has long been recognized as an important part of the overall field of medical computing, as well as a complex and varied field in its own right. There are a number of purposes for which such an evaluation might be performed. This paper focuses on one of those purposes, the assurance of safety when preparing to release the system for general use. The assurance of safety involves two major stages: (1) a comprehensive validation of the system's knowledge and advice, and (2) a period of use which exposes the system's advice and interface to the clinical environment. PMID- 2232955 TI - Evaluation stages and design steps for knowledge-based systems in medicine. AB - After the early experiments in artificial intelligence a methodology is emerging around advanced systems for the management of medical knowledge. The stress is moving away from the implementation of prototypes to the evaluation. It is possible to adapt and to apply this to field evaluation techniques already developed in similar contexts of knowledge management (books, drugs, epidemiology, consultants, etc.). The time is ready for a further step: to envisage a methodology for the design of real systems that cope with the 'knowledge environment' of the user. Every stage of the evaluation process is re examined here, and considered as a framework to define goals and criteria about a step of design: (1) the impact of the system on the progress of health care provision (priorities, cost-benefit analysis, share of tasks among different media); (2) effectiveness in the end-user's environment and long-term effects on his behaviour (changes in people's role and responsibilities, improvements in the quality of data, acceptance of the system); (3) the intrinsic efficiency of the system apart from the operational context (correctness of the knowledge base, appropriateness of the reasoning). The need to differentiate the test sample into three classes (obvious, typical, atypical) is emphasized, discussing the influence on both evaluation and design. In particular the difficulty of having 'gold standards' on atypical cases, due to the disagreement among the experts, leads to the definition of two alternative attitudes: the 'standardization mode' and the 'brain-storming mode'. PMID- 2232956 TI - Evaluating medical expert systems: what to test and how? AB - Many believe that medical expert systems have great potential to improve health care, but few of these systems have been rigorously evaluated, and even fewer are in routine use. We propose the evaluation of medical expert systems in two stages: laboratory and field testing. In the former, the perspectives of both prospective users and experts responsible for implementation are valuable. In the latter, the study must be designed to test, in an unbiased manner, whether the system is used in clinical practice, and if it is used, how it affects the structure, process and outcome of health care encounters. We conclude with proposals for encouraging the objective evaluation of these systems. PMID- 2232957 TI - The evaluation of decision aids: the role of the decision owner. AB - This paper is a discussion of the role patient preferences should play in the evaluation of medical decision aids. The use of 'practitioner acceptability' as an unproblematic criterion in the evaluation of such aids is questioned, along with the wider imbalance in resource allocation between research relevant to the 'technical' and 'value' aspects of medical decision-making. PMID- 2232958 TI - Evaluating black-boxes as medical decision aids: issues arising from a study of neural networks. AB - The rigorous evaluation of medical decision aids will be critical to promoting their development, establishing their clinical value and legalizing their use. Many decision aids are transparent in the sense that their internal structure and function can be examined and verified. Some decision aids, however, use complex models of associations in training data to construct 'black-box' systems whose workings are largely impenetrable and inexplicable. The issues surrounding the evaluation of such systems, as exemplified by connectionist (neural network) models, are discussed. For such systems the two major aspects that can be evaluated are the training data from which the system is derived, and its performance on test data. A number of questions about the use of black-box systems as medical decision aids are posed which require consideration by the medical informatics community. PMID- 2232959 TI - Evaluating and validating very large knowledge-based systems. AB - Most knowledge-based systems for use in medicine have been developed in response to specific problems such as the diagnosis of abdominal or chest pain in an accident and emergency department, or the diagnosis and treatment of meningitis. There is a role for a general decision support system capable of answering queries about any aspect of medicine, particularly in primary care. However, evaluating such a knowledge base requires more elaborate methodology than a simple iterative test and refine cycle. At the design stage an adequate knowledge base structure is required to allow focused modification of the knowledge base when errors are discovered. During the prolonged evaluation cycle the partially formed knowledge base must be tested with such techniques as validation checks for consistency and completeness and examination of characteristics of problem solving procedures. Finally a variety of criteria that represent the performance, robustness, flexibility, predictability, validity, coverage, relevance and congruity of the knowledge base are needed for a full description of the system's worth. Two case studies from the Oxford System of Medicine project are provided as examples of this philosophy: validating specific medical facts and comparing two methods for aggregating reasoning for and against a decision option. PMID- 2232960 TI - Human-computer interface evaluation: not user-friendliness but design for operation. AB - This paper considers human-computer interface evaluation in the context of design and development. It is argued that it is not helpful to view evaluation as a method for achieving user-friendliness, rather it should be seen as a participating activity within design and development. The centre of concern is the operation of the system when employed in practice. Such evaluation is not necessarily to be conducted by independent observation and experiment, but may be closely integrated with other design activities. In fact the very theory underlying the evaluation finds its embodiment in the artifact of the user interface. Taking this view has technical, as well as human factors, implications. PMID- 2232961 TI - Field trials of Baby Check: a scoring system to quantify illness in babies under 6 months. AB - Baby Check, a scoring system for quantifying illness in young babies, was developed from a study of 1007 well and ill babies in Cambridge and Melbourne. This paper describes the setting up of field trials to test the performance of the scoring system when used by mothers, GPs and hospital doctors. Preliminary results suggest that the scoring system is attractive, easy to use, useful and of high specificity. Its sensitivity to serious illness is also thought to be high but this will become clearer when the main hospital field trial has been completed. PMID- 2232962 TI - Assessing the clinical impact of a predictive system in severe head injury. AB - Many computer-assisted diagnostic or prognostic systems have been described in the literature, but as yet such systems have had little impact upon routine clinical practice. There are many possible explanations for the limited success which these systems have enjoyed, but one of the most significant must be the dearth of well-designed and carefully executed trials to assess their performance. Many evaluations only address the scientific question of whether the diagnoses or prognoses are accurate; they stop short of answering the crucial pragmatic question of whether the system benefits patients, i.e. is clinical care improved by the use of such a system? This brief paper describes a predictive system in severe head injury which has been developed by an international group based in the Institute of Neurological Sciences at the Southern General Hospital, Glasgow. The various steps involved were first the establishment of a clinical databank according to a strict protocol and with carefully designed scales to quantify the impairment of consciousness and outcome, the development of prognostic models relating outcome to initial severity, the comparison of the performance of this model with predictions made by clinicians, and finally a multi-centre prospective trial assessing the clinical impact of the system. The results of this trial are not yet available, but a consideration of the design of the trial raises important points which are relevant to many other clinical fields where 'decision aids' need to be evaluated. PMID- 2232963 TI - Evaluation of clinical decision aids--more to think about. AB - Validation and clinical testing of medical decision aids is a hot topic at present. We state a few main points which, in our opinion, have not received the attention they deserve. Our main concerns have to do with the statistical design and analysis of field evaluation studies; with long-term effects; and with the interplay between medicine and the software industry. The points represent our reaction to a recent symposium on the topic, published in this special issue. We take the opportunity to supplement the papers at hand in various ways and, where we see a risk of misconceptions or poor practice becoming cemented, try to point out the proper course. PMID- 2232964 TI - Does GABA act through dopaminergic/cholinergic interaction in the regulation of higher environmental temperature-induced change in body temperature? AB - Acute exposure of adult male albino rats to higher ambient temperature (40 degrees C) for 2 h significantly increased body temperature (BT). Administration of either bicuculline (1 mg/kg, i.p.), a GABA antagonist, or physostigmine (0.1 mg/kg, i.p.), an inhibitor of acetylcholinesterase, significantly increased BT of normal and heat-exposed rats. Treatment with muscimol (1 mg/kg, i.p.), a GABA agonist, produced hypothermia in normal rats and prevented an increase in BT of heat-exposed rats. The dopamine agonist, L-dopa (100 mg/kg, p.o.) along with carbidopa (10 mg/kg, p.o.) reduced BT of normal rats. Further, the bicuculline-or physostigmine-induced enhancement of BT in normal and heat-exposed rats was potentiated when both drugs were administered concomitantly. But this potentiating effect remained unaltered when dopamine antagonist haloperidol (1 mg/kg, i.p.) was administered along with bicuculline and physostigmine. Treatment with atropine (5 mg/kg, i.p.), a cholinergic antagonist, abolished the hyperthermic effect of bicuculline but potentiated the hypothermic effect of muscimol either at 28 degrees C or at 40 degrees C. Bicuculline-induced hyperthermia was attenuated at normal or higher temperature by pretreatment with L-dopa + carbidopa. The administration of L-dopa + carbidopa either abolished or reduced the hyperthermic effect of physostigmine at room temperature or at higher ambient temperature. These results suggest that (a) GABAergic, cholinergic and dopaminergic systems are involved in thermoregulation, (b) exposure to high environmental temperature may inhibit central GABAergic activity which activates the cholinergic system without affecting the dopaminergic system and raises BT, (c) central dopaminergic and GABAergic systems act independently through the modulation of cholinergic activity in the regulation of BT under normal ambient temperature. PMID- 2232965 TI - Rheoencephalographic and electroencephalographic studies on nicergoline. AB - The effect of nicergoline on the rheoencephalogram (REG) and on spontaneous electroencephalographic activity (EEG) was studied in acute experiments in cats. The following REG parameters were assayed: amplitude, anacrotic section of the curve and its relative part and dicrotic index. EEG spectra were derived from 10 sec samples of ECoG and the relative amplitude was estimated at 2 Hz-intervals from 0-44 Hz. The REG study showed that nicergoline (0.05 mg/kg i.v.) caused an increase of the amplitude, and a decrease of the anacrote, of the relative part of the anacrote and the dicrotic index - changes indicating a lowering of cerebrovascular resistance. EEG study showed a decrease of the slow activities (theta and delta), and an increase of the fast activities (alpha and beta-1). PMID- 2232966 TI - Investigations on cell-mediated immunity in patients with breast and ovarian carcinomas receiving a combination of chemotherapy and immunotherapy with thymopentin. AB - In 78 patients with breast and 37 patients with ovarian cancer the effect of combined chemo- and immunotherapy with thymopentin (Timunox, Cilag) on different parameters of cell-mediated immunity (leukocyte migration inhibition test, serum level of TNF-alpha, IL-1, interferon-alpha, distribution of lymphocyte subsets) and the clinical course of disease was evaluated and compared to patients receiving only chemotherapy. In cancer patients additionally treated with thymopentin an increase in reactivity in the LMI test and an increase of IFN alpha serum levels could be observed, whereas serum levels of TNF-alpha and IL-2 and the distribution of T-helper, T-suppressor, total T and natural killer cells did not change. Concerning the clinical course of disease, no significant differences could be observed in patients with disseminated spread of disease, whereas in patients receiving combined chemo-immunotherapy in the course of an adjuvant treatment a benefit was found compared to those receiving only chemotherapy. Thus, it seems that the additional administration of thymopentin in breast and ovarian cancer patients under chemotherapy results in a reduction of immunosuppressive side effects of chemotherapy and a positive effect of the survival time in patients with limited spread of disease. PMID- 2232967 TI - Histaminergic system: neuroendocrine function of brain histamine. PMID- 2232979 TI - [Roots of the health care crisis--a perspective on its development]. PMID- 2232968 TI - The medical history of waters and spas. Introduction. PMID- 2232980 TI - [Curtail prolonged compulsory isolation in the departments of infectious diseases]. PMID- 2232982 TI - [How should the progress of cancer prevention be measured?]. PMID- 2232981 TI - [Antibiotic resistance of anaerobic bacteria--an increasing clinical problem]. PMID- 2232983 TI - [Increased incidence of carpal tunnel syndrome in dialysis patients]. PMID- 2232984 TI - [Let us avoid cholesterol tests performed by pharmacies!]. PMID- 2232985 TI - [Shall we stop to use Miraxid?]. PMID- 2232986 TI - [A pilot study shows incompletely filled out forms at maternal health care and obstetric centers]. PMID- 2232987 TI - [Eye movements during normal reading and in dyslexia--review of the literature]. PMID- 2232989 TI - [Sufficient national supply of all blood products--a pressing goal]. PMID- 2232988 TI - [Chronic pain patients with well-defined diagnosis feel better than patients with unclear diagnosis]. PMID- 2232990 TI - [Virginia Apgar Award to Petter Karlberg. After 45 years of pioneering commission as a pediatrician, the research on body-soul-environment is tempting]. PMID- 2232991 TI - [Strong arguments against legalization of euthanasia]. PMID- 2232992 TI - [Intensive care of extremely low birth weight infants--is selection by prognosis ethically acceptable?]. PMID- 2232993 TI - [Future needs of rheumatology. A young specialty with expanding content]. PMID- 2232994 TI - [Ethics and interest conflicts--a question not only for general practitioners]. PMID- 2232996 TI - [A new therapeutic program. Thrombolysis in myocardial infarction and treatment of unstable coronary disease]. PMID- 2232995 TI - [A new study: unclear results of psychotherapy in schizophrenia. Better to wait than to create false expectations]. PMID- 2232997 TI - [Migraine as a sociomedical problem]. PMID- 2232998 TI - [Psychotherapy in schizophrenia--a prospective study]. PMID- 2232999 TI - [The family--an underestimated but heavily burdened resource in health care]. PMID- 2233001 TI - [Along the Silk Road and in Sweden. Behcet's syndrome--a rare systemic disease affecting mostly younger persons]. PMID- 2233000 TI - [Diet and health. The process of civilization brings about change of dietary habits]. PMID- 2233002 TI - [The man behind the syndrome. Hulusi Behcet. He performed a detailed survey of the syndrome with mouth ulcers, iritis and genital ulcers]. PMID- 2233003 TI - [Endoscopic thoracic sympathectomy. A surgical method employed in severe hand sweating]. PMID- 2233004 TI - [The right to starve and die--reject legislation]. PMID- 2233005 TI - [A Swedish model for psychosocial relief work. A group takes care of the persons hit by disasters]. PMID- 2233006 TI - [The Nobel Prize. This year's prize-winners are rewarded for clinical methods]. PMID- 2233007 TI - [Scandinavian guidelines for clinical trials]. PMID- 2233008 TI - [Drugs exist--but changing of life style can be sufficient in the prevention of osteoporosis]. PMID- 2233009 TI - [The USA report on cardiovascular disease research and (un)equality: white middle aged men as a norm for the whole population]. PMID- 2233010 TI - [Implantation of defibrillators--a final measure at German clinics]. PMID- 2233011 TI - [Hippocratic respect for patients' self-determination?]. PMID- 2233012 TI - [Physical activity has a certain positive effect on the skeleton]. PMID- 2233013 TI - [British treatment of autism. High scientific level in spite of small resources]. PMID- 2233014 TI - [A center for rehabilitation technology at the Lund Institute of Technology. A dynamic workshop of ideas activating research of everyday rehabilitation technology]. PMID- 2233015 TI - [Is waiting for surgery more difficult in Stockholm than in rural areas?]. PMID- 2233016 TI - [Histamine and methacholine tests in cases of sensitive bronchi--a 10-year experience]. AB - Ten years' experience of standardised bronchial histamine and methacholine tests is presented. For measuring non-specific hyperreactivity was used an internationally adopted dose-response technique, where histamine or methacholine is inhaled at doses increasing in two-fold steps. The fields of application have been clinical research on hyperreactivity, the diagnosis of asthma, evaluation of anti-asthmatic drugs, establishing (or excluding) the presence of bronchial obstruction or functional breathing disorder--the latter being a relatively new field. On the basis of this experience, the existence of a relationship between subjective hyperreactivity and breathing complaints has been hypothesized; and in clinical studies the place of histamine and methacholine tests as diagnostic aids in cases of bronchial asthma or functional breathing disorder has been better established. The tests yield information as to any tendency to develop bronchospasm, but must always be combined with other diagnostic tests and the taking of a careful history. Some important findings are reported--e.g., abnormal and steep dose-response curves, false low FEV1 values, or the occurrence of non asthmatic symptoms during testing--which have not previously been fully considered in published reports, and which may lead to incorrect interpretation of test results. PMID- 2233017 TI - [Borderline conditions--a difficult terminology problem, but an interesting exercise in creativity]. PMID- 2233018 TI - [Information and general guidelines for prescription of psychopharmaceuticals]. PMID- 2233019 TI - [A consulting group for ethical questions in perinatology--experiences from the Ostra hospital in Gothenburg]. PMID- 2233020 TI - [Diagnosis of cystic fibrosis by means of genetic technology--guidelines from an expert meeting]. PMID- 2233021 TI - [Organizational problems behind the casualties in health care--why don't we learn more from experience?]. PMID- 2233022 TI - [How does molecular biology influence clinical research and health care in the 1990's?]. PMID- 2233023 TI - [Segmental pain--can the patients be identified and treated successfully?]. PMID- 2233024 TI - [Child stammering. Parental anxiety is the most important referral indication]. PMID- 2233025 TI - [England is en example for Sweden concerning psychiatric care. Lobbying inspires politicians to reforms]. PMID- 2233026 TI - [Rehabilitation of schizophrenic patients demands an individually based combination of psychosocial therapy and medicine]. PMID- 2233027 TI - [Preliminary experiences show good results. Extracorporeal membrane oxygenation in respiratory insufficiency in children]. PMID- 2233029 TI - Belching caused inversion of the inserted gastroscope. PMID- 2233028 TI - [Extracorporeal membrane oxygenation as a life-saving method in neonatal pneumonia]. PMID- 2233030 TI - [Kleine-Levin syndrome--an unusual behavioral disorder in young men]. PMID- 2233031 TI - [High incidence of cerebral concussion among elite ice hockey players]. PMID- 2233033 TI - [The Karolinska institute: a trial of local admission will broaden the selection of students to medical schools]. PMID- 2233032 TI - [Diagnostic equipments owned by neonatal departments make their use more efficient]. PMID- 2233034 TI - [Problems with narcotics at the workplace]. PMID- 2233035 TI - [Forbid beards among health personnel]. PMID- 2233036 TI - [Can spermatocidal agents give protection even against HIV?]. PMID- 2233037 TI - [Pregnancy in diabetes and fetal abnormalities--importance of a strict insulin therapy regimen]. PMID- 2233038 TI - [Do not forget tuberculosis screening of pregnant immigrant women]. PMID- 2233039 TI - [Greatly increased number of elective surgery of aortic aneurysm]. PMID- 2233040 TI - [Surgical or non-surgical abdominal aortic aneurysm--the choice of treatment is based on the size of the aneurysm]. PMID- 2233041 TI - [Management of visceral aneurysm]. AB - In the article we discuss our experience in dealing with visceral aneurysms at Malmo General Hospital during the period, 1971-85. Of the total of 25 patients diagnosed, eight had ruptured aneurysms, six underwent elective surgery, and 11 underwent no surgical intervention. Of the aneurysms found, nine were of the splenic artery, five of the superior mesenteric artery and its branches, three of the pancreaticoduodenal artery, two of the celiac artery, and one of the gastroduodenal artery. There was no mortality either among patients undergoing surgery, or from complications among those treated conservatively without surgery. PMID- 2233042 TI - [Education, chemotherapy and a vaccine can stop increasing of schistosomiasis]. PMID- 2233043 TI - [The man behind the syndrome. Theodor Bilharz. He tried to explain the mystery of the worm--it is still a big global health problem]. PMID- 2233044 TI - [Acute schistosomiasis can be diagnosed by early serology]. PMID- 2233045 TI - [Impaired pulmonary function after welding of painted steel]. PMID- 2233046 TI - [Lars Olof Kallings appointed as an advisor on AIDS questions at the WHO. The rapidly developed laboratory research on HIV/AIDS makes the WHO to guard carefully the research ethics]. PMID- 2233047 TI - [Dynamic development of the research on a vaccine and drugs against HIV]. PMID- 2233048 TI - [Women and AIDS as the topic of the international AIDS day this year]. PMID- 2233049 TI - [Cheap copies are a threat to research]. PMID- 2233050 TI - [Rehabilitation for 15 billions--a humanitarian endeavor or a futile effort]. PMID- 2233051 TI - [Is obstetric analgesia hazardous to the newborn infant?]. PMID- 2233052 TI - [A neuroorthopedic clinic for the management of vertebral column injuries]. PMID- 2233054 TI - [Headache among the young is more frequent than thought. Promising methods in tension headache]. PMID- 2233053 TI - [Disorders caused by video display terminals and hypersensitivity to electricity- the affected persons experience a cruel reality]. PMID- 2233055 TI - [Swedish research-workers in neurology showered with awards]. PMID- 2233056 TI - [Promising new results with transplantation of nerve cells to the brain in Parkinson disease]. PMID- 2233057 TI - [Tonsillectomy--an old-fashioned therapeutic method in recurrent tonsillitis]. PMID- 2233058 TI - [Families with hereditary cancer--a target group for prevention]. AB - Although a large proportion of the population contract cancer, the risk is not uniform. In a small group (an estimated five per cent) with hereditary predisposition, the risk of cancer is high (often as high as 50 per cent) in every child of an affected parent. Another, considerably larger group consists of individuals at high risk (though how high is unknown), where a combination of hereditary and environmental factors is probably involved. In all likelihood, it is this group which would benefit most from general recommendations as to preventive measures. The study of such individuals will enhance our knowledge of the source of their vulnerability, thus facilitating the understanding of tumorigenic mechanisms in general, and on the basis of such knowledge improve the prospect of general and specific screening programmes, prevention and treatment. PMID- 2233059 TI - [Losec after 2 years: satisfactory safety of short-term therapy]. PMID- 2233060 TI - [Can the quality of surgery be guaranteed in the future?]. PMID- 2233061 TI - [Care strategies in North America: strengthened nurses' role and intense concentration on leadership]. PMID- 2233062 TI - [Prevention of pre-eclampsia with ASA--continuous caution is recommended]. PMID- 2233063 TI - [Investigation of sexual child abuse: professionalism--an absolute necessity]. PMID- 2233064 TI - [Work and sick-listing seen from a Scandinavian perspective]. PMID- 2233065 TI - [A consensus on dementia diseases (I): Classification and investigation]. PMID- 2233066 TI - [Benign cyst can signal tonsillar cancer]. PMID- 2233067 TI - [Toxic hepatitis after exposure to dimethylformamide]. PMID- 2233068 TI - [Adrenomyeloneuropathy--an unusual X chromosome-linked disease]. PMID- 2233069 TI - [Cervical manipulation can cause cerebral infarction]. PMID- 2233070 TI - [Diet during childhood and adolescence can influence health even in adulthood]. PMID- 2233071 TI - [A medical controversy: is orthopedic medicine needed? (1). Development within scientific medicine can be more effective in musculoskeletal pain]. PMID- 2233072 TI - "Tissue welding" with the argon laser in middle ear surgery. AB - Over the past 10 years the argon laser has been recognized as a valuable adjunct to middle ear surgery. It has been used to vaporize and cut tissue and to coagulate microbleeding. It has been used by many other surgical specialties to "weld" adjacent tissues together. This welding process appears to have a limited but helpful role in middle ear surgery. A pilot study of 30 surgical cases in which argon laser "tissue welding" has been used are reported. The benefits, limitations, and possible future implications are discussed. PMID- 2233073 TI - Efficacy and morbidity of partial laryngectomy and postoperative radiation therapy. AB - In recent years, we have seen increasing use of partial laryngectomies for larger lesions that were previously treated by total laryngectomy. The resultant closer margins have made postoperative radiation therapy an important adjuvant treatment to conservation laryngeal surgery. We review the University of California, Los Angeles, experience with combination partial laryngectomy and postoperative radiation therapy between 1973 and 1987 for treatment of carcinoma of the larynx. Twenty-four such patients who underwent partial laryngectomies and postoperative radiation therapy are examined. Techniques of treatment, complications, and the functional ability of the remaining larynx are discussed. The locoregional control rate at 5 years was 80%. Risk factors associated with an increased risk of recurrence were positive margins, vascular invasion, and extranodal spread. There were no major problems with postoperative wound healing or airway management during the radiation treatment. Vocal and swallowing function were well preserved in most cases. We conclude that combination partial laryngectomy and radiation therapy permits preservation of laryngeal function without serious complications, and therefore is an effective treatment for selected patients with carcinoma of the larynx. PMID- 2233074 TI - Auditory-evoked responses in benign intracranial hypertension syndrome. AB - In this study, auditory brainstem-evoked responses were conducted on 28 patients with otologic symptoms (pulsatile tinnitus, hearing loss, aural fullness) secondary to benign intracranial hypertension syndrome. Abnormalities consisting mainly of prolonged interpeak latencies were detected in one third of these patients. It is speculated that the pathophysiologic mechanisms responsible for these auditory brainstem-evoked abnormalities are stretching-compression of the cochlear nerve and brainstem caused by the intracranial hypertension and/or primary edema of the same structures due to the benign intracranial hypertension syndrome itself. Normalization or improvement was noticed in the majority of the patients after management. Since the number of patients in this study is small, it is felt that the diagnostic and prognostic value of this test needs further evaluation. PMID- 2233076 TI - Computed tomography staging of the paranasal sinuses in chronic hyperplastic rhinosinusitis. AB - In this study, the computed tomography scans of 100 patients with chronic hyperplastic rhinosinusitis were reviewed to establish a clinical staging system. Fourteen percent of the patients were classified as Stage I (single-focus disease); 36% as Stage II (multifocal disease responsive to conservative therapy); 32% as Stage III (diffuse disease partially responsive to medication); and 16% as Stage IV (diffuse disease associated with bony changes and poorly responsive to conservative treatment). The incidence of recurrent or persistent disease ranged from 13% for Stage II to 30% for Stage IV. Stage I and III patients had 13% and 18% recurrence rates, respectively. Computed tomography staging is shown to be useful in outlining operative strategies and is a reliable prognosticator of the disease process. PMID- 2233075 TI - Angioedema from angiotensin converting enzyme inhibitors: a cause of upper airway obstruction. AB - Angiotensin-converting enzyme (ACE) inhibitors have several side effects of concern to the otolaryngologist. Angioedema is a rare, but potentially lethal adverse effect when associated with upper airway obstruction. Four cases of ACE inhibitor-induced angioedema, three with significant upper airway obstruction, are reported. Angioedema secondary to ACE inhibition appears to be mechanism based. The probable link is the potentiation of bradykinin, which results in vasodilation, increased vascular permeability, and angioedema. Since angioedema can progress to upper airway obstruction, otolaryngologists must be aware of this association. The differential diagnosis and treatment of this adverse effect is discussed, as well as a review of ACE inhibitors and other causes of angioedema. PMID- 2233077 TI - Intraoral-extramaxillary sinus approach for ligation of the maxillary artery: an anatomic study with clinical correlates. AB - Surgical control of severe epistaxis is usually reserved for cases refractory to more conservative techniques. We present our experience with intraoral ligation of the maxillary artery as it courses through the buccal fat pad before it enters the pterygopalatine fossa and branches posterior to the maxilla. This technique has been found useful in the control of nasal hemorrhage as well as an adjunct to other surgical procedures, such as removal of benign and malignant neoplasms involving the maxilla and paranasal sinuses. This technique was used for ligation of the maxillary artery in 20 patients. The artery was readily identified in some cases, but required more extensive dissection in others; therefore, an anatomic study in 18 preserved and fresh cadaver specimens was undertaken to investigate the variability of the maxillary artery in the region of the buccal fat pad. There appeared to be significant variation in the distance from the buccal mucosal incision site, as well as variation in the relationship to the pterygoid muscles. This relationship to the pterygoids explains the occasional difficulty in locating the artery for ligation. This technique represents a reasonable alternative to the more traditional transantral approach to ligation of the maxillary artery, as long as the surgeon understands the anatomy of the region, its variations, and where the artery may be located if not immediately apparent. No major complications have been experienced. PMID- 2233078 TI - The efficacy of brainstem auditory evoked potentials in acoustic tumor surgery. AB - As the identification of patients with small acoustic neuromas and salvageable hearing increases, intraoperative auditory nerve monitoring has been used increasingly in an attempt to improve the hearing preservation rate. Far-field recordings obtained by brainstem auditory evoked potentials (BAEP), at times enhanced by electrocochleography, have become a standard method of intraoperative auditory nerve assessment. To evaluate the usefulness of this monitoring technique, the hearing preservation results of a series of unmonitored acoustic tumor removals were compared to a series of patients monitored via the standard brainstem auditory evoked potentials. With comparable average tumor sizes, 4 of 7 unmonitored patients had hearing preserved at preoperative levels compared to 4 of 9 monitored patients. Neither preoperative BAEP assessments nor absolute tumor size were predictive of hearing preservation. This report brings into question the effectiveness of far-field intraoperative BAEP monitoring during acoustic tumor resection and suggests that direct auditory nerve monitoring may be more appropriate. PMID- 2233079 TI - Vocal cord paralysis in children. AB - Bilateral vocal cord paralysis is a common cause of stridor in infants and children. There are significant differences in this entity between children and adults with regard to etiology, diagnosis, management, and outcome. A review of 10 years' experience at Children's Hospital of Philadelphia identified 51 children seen with the diagnosis of vocal cord paralysis. These cases were evaluated with respect to etiology of paralysis, whether unilateral or bilateral, delay in diagnosis, need for tracheotomy, abnormality of voice, surgical treatment, and outcome. Guidelines for management for a child with vocal cord paralysis are presented with emphasis on flexible endoscopic evaluation and conservative management. PMID- 2233081 TI - Evaluation of neonatal subglottic stenosis: a 3-year prospective study. AB - Subglottic stenosis is the most common cause of chronic airway obstruction. It results in prolonged tracheal cannulation of infants and children. Following the widespread adoption over the past 20 years of prolonged intubation for respiratory support in neonates, the incidence of acquired subglottic stenosis increased dramatically. On January 1, 1987, we began a 3-year prospective study to delineate potential etiologic factors involved in the development of subglottic stenosis in neonates. The present study analyzes data from 289 infants. Relationships between birth weight, gestational age, endotracheal tube size, duration of intubation and ventilation, number and difficulty of intubations, and the subsequent need for medical and surgical therapy are discussed. Whole organ larynges from autopsy specimens provide histological correlation. PMID- 2233080 TI - Myogenic influences on the electrical auditory brainstem response (EABR) in humans. AB - Two cases demonstrating the effects of myogenic artifact on the electrical auditory brainstem response (EABR) when using a promontory stimulation site are presented. Intensity-response functions were obtained in the unparalyzed condition, then repeated after infusion of a neuromuscular paralyzing agent. In both cases, the myogenic response was observed at lower stimulus intensities than the EABR components. As intensity increased, the myogenic responses grew at extremely rapid rates and made any subsequent identification of auditory responses virtually impossible. To alleviate the adverse influence of myogenic components, general anesthesia and a paralyzing agent must be incorporated into the test protocol when acquiring the EABR using a promontory site of stimulation. PMID- 2233082 TI - 1990 Ogura memorial lecture: moral dilemmas in head and neck cancer. AB - Neither morality nor dilemma can be defined meaningfully in the concept of the practical management of head and neck cancer. Although both have important implications, particularly with regard to ethnic and social factors, they play a relatively minor role in determining management policy. With little knowledge of the intrinsic causes of cancer and with a treatment strategy limited to radiotherapy and surgery, our desire for cure must be tempered by concern to avoid any increase in patient privations. My philosophy, based upon the care of more than 3500 patients over almost 30 years, reflects some of the difficulties of applying the concept "do nothing that may cause harm," while offering each patient the opportunity for long-term cure. PMID- 2233083 TI - The efficacy of comprehensive neck dissection with or without postoperative radiotherapy in nodal metastases of squamous cell carcinoma of the upper respiratory and digestive tracts. AB - Neck recurrence-free curves corrected for local recurrence were compared for 494 patients who underwent 565 comprehensive neck dissections. In 42 dissections, no radicality could be obtained. Of the 523 histologically radical dissections, examination revealed tumor in 352 cases. Patients in whom three or more positive nodes or extranodal spread in one or more nodes were found received postoperative radiotherapy. In the histologically N0 group, the incidence of neck recurrence after 5 years was 3%; in the N+ group as a whole, it was 10%. Analysis of the influence of extranodal spread and the number of positive nodes showed that the group with one or two positive nodes without extranodal spread (that did not receive postoperative radiotherapy) did not statistically differ from the other groups. This suggests that the results of the group with one or two positive nodes without extranodal spread can be improved by postoperative radiotherapy. PMID- 2233084 TI - Esthesioneuroblastoma: surgical treatment without radiation. AB - This study compares the treatment of two groups of patients diagnosed with esthesioneuroblastoma limited to the nasal cavity without evidence of cribriform plate erosion. Five patients were treated with radiation and extracranial excision, and eight patients were treated by craniofacial resection only. The incidences of local recurrence were 60% and 12%, respectively. The paper also presents a new staging classification for these tumors. PMID- 2233085 TI - A new low-resistance, self-retaining prosthesis (Provox) for voice rehabilitation after total laryngectomy. AB - Prosthetic rehabilitation of voice after total laryngectomy has gained wide acceptance in the last 10 years. Several reliable voice prostheses have been developed and used successfully. Priorities for further development of the methods and instruments for prosthetic voice rehabilitation have led to the design of a low-resistance, self-retaining voice prosthesis (Provox) and an adapted replacement method. The results obtained in 79 patients are described. In vivo airflow resistance ranged from 1.0 to 3.8 kPa (mean = 1.9 kPa). Speech quality was good in 91% of the patients. The self-retaining properties of the prosthesis appeared to be satisfactory. The average device-life was more than 5 months. Replacement of the prosthesis with a new disposable guide wire was done quickly as an outpatient procedure. Maintenance of the prosthesis by the patient was simple. The new low-resistance, self-retaining Provox voice prosthesis and the modified replacement method appeared to further improve the results of prosthetic voice rehabilitation after total laryngectomy. PMID- 2233086 TI - Carcinoma of the external auditory canal: an update. AB - This review is a continuation of the series of 35 cases of carcinoma of the external auditory canal originally reported by the senior author and colleagues. Eighteen additional cases have been evaluated and treated since 1976. Preoperative high-resolution computed tomographic scanning has replaced polytomography, and improved surgical skull base approaches have allowed for extended resections of advanced lesions. A revised classification for local and extensive lesions is presented. The prognosis for localized tumors treated by en bloc resection remains excellent, whereas prognosis for extensive lesions might be more dependent on histologic type and grade of tumor. PMID- 2233088 TI - Indications of the carbon dioxide laser in tracheobronchial pathology of the infant and young child: 14 cases. AB - Fourteen children aged between 6 months and 7 years (mean age = 3.5 years) were treated by CO2 broncholaser in the ENT Department of Trousseau Hospital. Three groups of diagnostic indication were identified: 1. Granulomas treated after mucosal trauma (tracheotomy, foreign body). 2. Granulomas due to pulmonary and/or lymph node tuberculosis. 3. Adhesions and stenosis secondary to neonatal ventilation. The operative and anesthetic technique is described in detail, together with any possible adverse events. The CO2 broncholaser appears to be a technique of choice in this age group, in which the narrowness of the airways makes any endoscopic procedure difficult. The broncholaser allows the early treatment of obstructive tracheobronchial pathology with its risks of severe ventilatory sequelae. PMID- 2233087 TI - Artificial restoration of voice. I: Experiments in phonatory control of the reinnervated canine larynx. AB - Coordinated electronic pacing of implanted nerve pedicles into paralyzed laryngeal muscles has allowed selective dynamic control of abduction, adduction, and elongation of the vocal cords. Modifications of the original circuit in a cervical muscle model has added fine tuning to basic "all-or-none" pacing. Rehabilitation of phonation illustrated the sophisticated nature of voice and the need for restoration of fine tuning. Five mongrel dogs received nerve-muscle pedicles into the thyroarytenoideus, cricothyroideus, and posterior cricothyroideus after denervation of one hemilarynx. Following appropriate reinnervation time, pedicles and intact recurrent laryngeal nerves were injected with currents of variable amplitudes and pulse widths to achieve graded vocal fold control while air was blown intratracheally towards the glottic chink. Videoscopic and spectral analyses indicated that artificial phonation could be restored to frequencies measured in the normal state. These experiments suggested that rehabilitation of the impaired voice by servocontrol might eventually be feasible. PMID- 2233089 TI - An in vivo canine model for testing treatment effects in laryngeal hyperadduction disorders. AB - Adductor spastic dysphonia is a voice disorder characterized by a strained, squeezed, effortful voice produced by true and false cord hyperadduction. An in vivo canine model has been developed to simulate hyperadduction of the true cords. Using this model, the thyroarytenoid muscle was found to have a greater effect on intraglottic and subglottic pressure than cricothyroid muscle contraction. The intraglottic and subglottic pressure was reduced after simulated recurrent laryngeal paralysis. This model can be used in future studies to compare laryngeal treatment modalities for disorders that have a component of vocal cord hyperadduction, such as spastic dysphonia. PMID- 2233090 TI - Variations on the temporoparietal fascial flap. AB - An improved understanding of the vascular supply of the layers of the temporal fossa has increased the potential of this region for new and ingenious reconstructive techniques. Separate and independently vascularized layers of this region include hair-bearing scalp, glabrous skin, tempororoparietal fascia (and galea aponeurotica), temporalis muscle and fascia, and pericranium. Island flaps of glabrous skin and scalp provided esthetically appropriate tissue to cover a variety of defects. The malleable bulk of the subcutaneous fascial layers were combined with skin grafts to restore thin lining, and used as a vascularized bed for cartilage grafts in otherwise unsatisfactory recipient sites. Illustrative cases from our 5-year clinical experience are presented to demonstrate various combinations of the temporoparietal fascial pedicle with tissues from the temporal region to reconstruct the eyebrows, eyelids, orbits, cheeks, and lips. PMID- 2233091 TI - Titanium lag-screw osteosynthesis for the restoration of mandibular continuity in mandibular "swing" procedures. PMID- 2233092 TI - Incisive canal and pterygopalatine fossa injection for hemostasis in septorhinoplasty. PMID- 2233094 TI - Dependence of the XeCl laser cut rate of plaque on the degree of calcification, laser fluence, and optical pulse duration. AB - A XeCl laser with an optical pulse duration of 35 ns was used to determine the cut depth per laser pulse of postmortem human aorta as a function of laser fluence for four main categories of plaque development. The data indicate that the cut depth per pulse progressively decreases as the degree of calcification increases even at very high (100 mJ/mm2) laser fluences. A comparison was made between the XeCl laser cut rate data obtained using the 35-ns duration laser pulses to data obtained using 200-ns duration pulses for each of the four plaque types. As the degree of tissue calcification increased higher XeCl laser fluences were required for the long pulse case to achieve the same cut depth per pulse as that observed using the shorter pulse duration. PMID- 2233093 TI - Holmium:YAG laser ablation of vascular tissue. AB - The ablation of atherosclerotic lesions without collateral thermal or shock wave damage is thought to be a key element for successful laser angioplasty. This study evaluated the effectiveness of pulsed holmium:YAG laser (2.1 microns wavelength) for this application. Fresh normal tissue (n = 139) and arteriosclerotic canine arteries (n = 21) as well as formalin-preserved normal canine (n = 31) and atherosclerotic human arteries (n = 177) were irradiated under saline via a 600 microns diameter fiber placed perpendicular to the intimal surface with 0-10 gm of force. The laser was operated in the free running mode (FRM; 250 microseconds pulsewidth, 5 Hz, 30-7,100 mJ/mm2) and in the Q-switched mode (QSM; 200 nsec pulsewidth, 6 Hz, 30-1,100 mJ/mm2). Following the experiments, the samples were prepared for histologic and morphometric analysis. Ablation thresholds in the FRM were 60 and 180 mJ/mm2 in fresh and preserved canine tissue, respectively. Ablation thresholds in the QSM for fresh and preserved canine tissues were 75 and 180 mJ/mm2, respectively. Thresholds for human atherosclerotic tissue were dependent on the amount of calcification. In the QSM and FRM, there were no samples that could not be penetrated at 1,100 mJ/mm2 and above. Histologic examination of the FRM samples revealed confined columns of tissue ablation, with approximately 55-250 microns and 70-140 microns zones of thermal effect being apparent in the fresh and formalin-preserved samples, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233095 TI - Thermal laser probe angioplasty: influence of constant tip temperature, plaque composition, and probe/vessel diameter ratio. AB - Thermal laser angioplasty uses constant laser power, producing widely variable tip temperatures in vivo. Results have been suboptimal. We studied the effect of 50-400 degrees C tip temperatures on depth of ablation at 192 sites on plaqued and normal human aorta in vitro, and the angiographic and histologic response in vivo of 300-400 degrees C at probe/vessel ratios of 0.5-1.0, in 40 normal canine femoral artery segments. In vitro, there was a direct relationship between tip temperature and depth of ablation, r = 0.71 (all segments), r = 0.74 for fibrous plaque, but a poor correlation in fatty plaque r = 0.35. In fibrous plaque, there was proportionately more ablation at tip temperatures greater than 300 degrees C, mean depth 0.62 mm, than at 150-300 degrees C, mean 0.37 mm, (P less than .001). Ablation was similar in plaqued and normal aorta. In vivo, 300 degrees C, 350 degrees C, and 400 degrees C produced similar effects. At probe/vessel ratios less than 0.8, only disruption of internal elastic lamina was observed. At ratios greater than or equal to 0.8, spasm occurred in 39% (7/18), transmural damage in 28% (5/18), and perforation in one of 18. Ablation is not selective for plaque and is highly variable in fatty plaque. Tip temperatures above 300 degrees C produce greater ablation than at lower temperatures. In clinical applications, probe/vessel rations less than or equal to 0.7 may be most appropriate, and it appears that thermal remodeling may contribute more to outcome than plaque ablation. PMID- 2233096 TI - Vasovasostomy in dogs using the carbon dioxide milliwatt laser: Part II. AB - This is the second study of a two-prong investigation conducted to learn two different aspects of vasovasostomy in dog vas deferens by using the carbon dioxide milliwatt laser. This investigation involves the evaluation of patency and analysis of sperm. Six dogs underwent vasectomy, followed by vasovasostomies performed between 4 and 12 weeks later, utilizing two approximating sutures and welding with the carbon dioxide milliwatt laser. Metal clips were used both for x ray analysis and localization of the vasovasostomy site. All dogs had pre vasectomy semen analysis. Following vasectomy each dog underwent ejaculation until azoospermia was obtained. Vasovasostomy was performed and semen was examined. Prior to harvesting, vasography was also obtained. All ejaculates had active sperm noted and 12 of 12 vasograms (100%) revealed patency. The dogs were sacrificed at 4 weeks, 6 weeks, and 8 weeks post-vasovasostomy. The vasovasostomy specimens were studied with electron microscopy and by histological evaluation. The vasovasostomy was completed in under 90 minutes by using this laser-assisted technique. This procedure offers to the urologist a more simplified and reproducible operation that can be performed easily and with a potential decrease in hospital costs. PMID- 2233097 TI - Carbon dioxide laser-assisted thyroarytenoid myomectomy. AB - CO2 laser-assisted myomectomy of the thyroarytenoid muscle (TA) was carried out through a thyroplasty approach in ten laryngeal specimens and the TA was examined histologically. Using the CO2 laser at super-pulsed mode, the TA can be cut or resected using 3-5 W of laser power. There is good control of the depth and extent of TA resection. Histologically, there is little evidence of collateral injury, with sparing of vital surrounding vocal structures. The use of CO2 laser for TA resection offers better access and surgical hemostasis in an otherwise difficult surgical field. Laser-assisted myomectomy may be a feasible alternative to current methods to treat spasmodic dysphonia. PMID- 2233099 TI - Lasers for otosclerosis--which one if any and why. AB - Laboratory stapedotomy and stapedectomy revisions were performed in human temporal bones while pyroelectric wave energy analyzers and ultrasensitive thermocouples measured energy absorption at the stapes footplate and in the vestibule. Analysis of these data shows that the visible lasers (argon and KTP 532) possess ideal optical properties and precision for otosclerosis surgery but conversely have less than ideal tissue characteristics. The CO2 laser possesses ideal tissue characteristics. Recent advances in optical engineering and pulsing the energy have increased the precision of this laser to now provide the accuracy required for delicate microsurgery. Two clinical studies analyze the long-term hearing results and complications in patients who had undergone CO2 laser stapedectomy revision (59 patients) and CO2 laser stapedotomy (153 patients). The advantages that these laser techniques provide over conventional surgery methods are discussed. PMID- 2233098 TI - Laser assisted fixation of ear prostheses after stapedectomy. AB - Three different lasers (erbium:YAG, holmium:YAG, alexandrite) were used to drill a hole at the end of the long process of the incus in order to fix an ear prosthesis after stapedectomy or small fenestra stapedectomy. The energy was coupled into a 250-microns core diameter zirconium-fluoride fiber. The operations were carried out on human temporal bone models from cadavers. The fiber was guided to the incus under the stereoscopic surgical microscope. The tissue response was examined under the scanning electron microscope, and after decalcification, histologically. These studies suggest the feasibility of using the erbium:YAG laser to improve the anchorage of the prosthesis on the incus and to increase the stability in ossicular chain reconstruction. PMID- 2233100 TI - Scanning electron microscopic study of laser-induced morphologic changes of a coated enamel surface. AB - A low-energy Nd:YAG laser was used to irradiate extracted human teeth coated with a black energy-absorbent laser initiator in a study to determine the extent of the morphologic changes produced in the enamel surface. The laser initiator was applied to a cleaned enamel surface and irradiated at an energy output of 30 mJ or 75 mJ. Both energy levels produced morphologic changes of the surface. There was a sharp line of demarcation between the coated, irradiated area and the surrounding noncoated enamel surface. The scanning electron microscope view at the lower energy level showed that the surface had melted and reformed with numerous small, bubble-like inclusions. The 75 mJ energy level showed individual impact craters with shallow centers and raised edges containing numerous pores and large, bubble-like inclusions. Etching is a dental procedure in which an acid is normally used to remove a thin outer layer of the tooth structure. This is necessary to create a roughened, irregular surface in order to provide mechanical retention for dental restorative materials. The changes produced by the laser in this study suggest a simple, effective, and controlled method of etching the enamel surface of a tooth by altering its surface characteristics. PMID- 2233101 TI - Laser in situ keratomileusis. AB - A new laser refractive procedure is being developed in a rabbit model. With a modified microkeratome, central corneal flaps were created. An ArF excimer laser was used to produce 3-mm-diameter circular ablations on the central part of the exposed stromal bed. One group of animals was sacrificed immediately postoperatively, and both the dissected and ablated areas were studied using scanning electron microscopy. A second group of animals was sacrificed 4 weeks postoperatively. In this group, the subsequent healing of the corneas was studied using light microscopy. At 3 days, the wounded stromal areas showed some degree of haze. Haze was progressively reduced over 1 month, but it could be still discerned biomicroscopically. A hemicircular opacification corresponding to the flap edges was also apparent on slit-lamp examination. Microscopic observation showed that the epithelium was normal, except at the flap margins, where it was thickened. An increased number of keratocytes was observed in the interface between the flap stroma and the ablated area. The procedure might induce stable corneal changes because of the preservation of the anterior layers of the cornea. PMID- 2233104 TI - [Expensive hospital? Current situation and perspectives]. PMID- 2233102 TI - Determination of retinal blood velocity with respect to the cardiac cycle using laser-triggered release of liposome-encapsulated dye. AB - A system of selective angiography has been developed for measuring blood velocity in retinal arteries and veins. It uses a liposome-encapsulated fluorescent dye that is released by application of laser energy in a specific retinal vessel. The method is shown to be able to distinguish between peak systolic velocity and minimum diastolic velocity. In the cynomolgus monkey, the two values were found to differ by approximately a factor of three. It is known that many ocular and systemic diseases affect retinal circulation, and therefore a method of blood velocity measurement with such sensitivity may prove highly valuable in the practice of ophthalmology. As an example, the velocity in a retinal vein was measured before and after partial occlusion by photocoagulation. The two values obtained were significantly different, and the blood velocity was found to return to the value prior to occlusion when measured at 18 days. PMID- 2233103 TI - Pulsed carbon dioxide laser ablation of burned skin: in vitro and in vivo analysis. AB - Pulsed lasers produce efficient and precise tissue ablation with limited residual thermal damage. In this study, the efficiency of pulsed CO2 laser ablation of burned and normal swine skin was studied in vitro with a mass loss technique. The heats of ablation for normal and burned skin were 2,706 and 2,416 J/cm3 of tissue ablated, respectively. The mean threshold radiant exposures for ablating normal skin and eschar were 2.6 J/cm2 and 3.0 J/cm2, respectively. Radiant exposures greater than 19 J/cm2 produced a plasma, which decreased the efficiency of laser ablation. Thus the radiant exposures for efficient ablation range from 4 to 19 J/cm2, and within this radiant exposure range 20-40 microns of tissue are ablated per pulse. We also examined, on a gross and histopathologic basis, in vivo burn eschar excision with a pulsed CO2 laser. The laser allowed bloodless excisions of full thickness burns on the backs of male hairless rats. The zone of thermal damage was approximately 85 microns over the subjacent fascia. The pulsed CO2 laser can ablate burn eschar efficiently, precisely, and bloodlessly and may prove valuable for the excision of burned and necrotic tissue. PMID- 2233105 TI - [Liver hemangioma. I. Diagnosis, spontaneous course, complications]. AB - Hemangioma is the most frequent benign tumor of the liver. Clinical signs range from complete absence of any complaints to the life threatening complication of hemorrhage. Ultrasound, computed tomography, angiography, scintigraphy and magnetic resonance tomography are appropriate diagnostic tools. The spontaneous course depends on diameter and localization of the tumor; the majority of complications are documented for hemangiomas of more than 5 cm in diameter and superficial position. PMID- 2233106 TI - [Detection of antibodies to Helicobacter pylori with the immunoenzyme test and indirect immunofluorescence]. AB - Sera from 56 adult patients were screened for the presence of IgG antibodies against Helicobacter pylori by enzyme immunoassay and indirect immunofluorescence. In addition, the detection of Helicobacter pylori in antral biopsy specimens was attempted by culture and histological methods. Colonisation of the antrum mucosa with Helicobacter pylori was observed in 39 of the 56 patients. IgG antibodies against Helicobacter pylori were detected by enzyme immunoassay in 34 of 39 infected patients. Thus, the enzyme immunoassay showed a sensitivity of 87.2 percent and a specificity of 82.4 percent. IgG antibodies against Helicobacter pylori were further detected by indirect immunofluorescence in 28 of 39 infected patients. Thus, indirect immunofluorescence showed a sensitivity of 66.7 percent and a specificity of 88.2 percent. Our results demonstrate that the enzyme immunoassay for IgG antibodies and other invasive or noninvasive methods for the detection of infection with Helicobacter pylori appear to be of equal sensitivity and specificity. PMID- 2233107 TI - [Myelolipoma of the adrenal gland]. AB - Myelolipomas of the adrenal gland are rare, nonfunctioning and benign tumors. The etiologic feature of these tumors, composed of fat and hematopoietic elements, remains unclear. Usually, myelolipomas of the adrenal gland, which are mostly asymptomatic, are recognized incidentally. Sonographic demonstration of the hyperechoic tumor combined with fine-needle aspiration biopsy reveals a prompt diagnosis. Computed tomography and adrenal angiography are complementary techniques. In most of the cases, a surgical treatment is indicated if the tumor becomes evidently symptomatic. PMID- 2233108 TI - [Critical analysis of drugs in 1989]. AB - Changes and trends in the drug field in the world and in Yugoslavia in 1989 are presented and discussed. 1. World. There appeared only a few new drugs all over the world, and new chemical entities (NCE) rather rarely represent a significant contribution to materia medica. Japan is the first in producing NCE (12) followed by United Kingdom and the USA (4 NCE each). 2. Yugoslavia. In Yugoslavia were 125 drugs discussed approval, new dose, new formulation or generic parallel. More than 84% of these have been related to generic or clinical ("me too") parallels; less than 9% of drugs had a certain contribution to materia medica, while, according to the authors, the number of drugs that contributed significantly to the materia medica and of those which should not have been approved was equal (3.2%). Octreotide, erythropoietin, almitrine and flumazenil were placed in category A. Insulin appeared in the largest number of parallels (as many as 19) succeeded by cardiovascular, antimicrobial and gastrointestinal drugs. 3. Drug formularies exist in all the developed countries and represent a way of limiting prescribing. Yugoslav list of drugs expenses of which will be covered by the Health Insurance will be prepared. 4. The Federal Institute for Health Protection through its special committee for diagnostics, pharmacotherapy and side effects represents a useful activity in rationalizing drug use. 5. Yugoslav publication of defined daily doses (DDD) is being prepared. 6. A review of causes of deficient or inadequate drug supply in Yugoslavia, which still represents a major problem in this country, has been given at the end. PMID- 2233109 TI - [The effect of leukocytes and erythrocytes on the metabolism and function of thrombocytes during preservation of thrombocyte concentrate at 22 degrees centigrade]. AB - The effect of leukocytes and erythrocytes on metabolic and functional changes was studied in 70 platelet concentrates kept for 72 hours at 22 degrees C in plastic PVC bags. On separating the platelet-rich plasma, a portion of buffy coat (i.e. a layer of leukocytes and erythrocytes) was added to one of the two series of platelet concentrates. These platelet concentrates did not differ from platelet concentrates prepared by the usual method, either by the platelet volume or count (p less than 0.05). The mean leukocyte count was 2.42 x 10(9)/L and 21.2 x 10(9)/L in the control and study series, respectively. After a 72 hour storage, a statistically significant difference (p less than 0.05) in the increase of lactate and ammonium concentrations, and a decrease in the glucose concentration and plasma pH were observed in platelet concentrates with a higher leukocyte count. The metabolic changes were accompanied by a statistically significant fall in the hypotonic shock (p less than 0.05). The results obtained in this study indicate that leukocytes in platelet concentrates elicit an adverse effect upon the platelet metabolism and function in vitro. In order to maintain the pH value at 6.0 during a 72 hour storage, the leukocyte count in platelet concentrates should not exceed 15.6 x 10(9)/L. PMID- 2233110 TI - [The effect of certain factors on the occurrence of sudden infant death syndrome]. AB - Although sudden infant death syndrome (SIDS) has been well known for a long time, in our country it has not been registered adequately yet and has seemed not to be present those years. But, it has not been true. A number of predisposing factors make that this phenomenon has a high share in postneonatal mortality, especially in those environments where the infant's mortality rate is low. A pathologist is imperative to establish a diagnosis following not only inadequate clinical picture and sudden death but also uncertain autopsy finding which does not make clear the cause of death in the majority of cases. In this paper, the frequency of SIDS during the epidemic of acute respiratory infection caused by respiratory syncytial virus being the potential indirect cause of the infants' deaths is presented. In 2/3 of cases this have been the infants born with perinatal risk factors and more often they have been males. SIDS has usually occurred at night, during autumn and winter and with infants coming from lower socio-economic and culturo-hygienic environments. In our environment, the frequency of SIDS has amounted to 22% of the total infant mortality rate. PMID- 2233111 TI - [An epidemic of legionellosis at a hotel at the Makarska seashore]. AB - The paper describes the epidemic of Legionellosis that occurred among guests and employees of a hotel at the Makarska littoral in May 1988. According to the so far reported data in the medical literature that was the third epidemic in our country and all three of them occurred in the Dalmatian touristic area. In this epidemic, nine foreign tourists were registered ill with the clinical picture of Legionnaires' disease. Five patients required hospitalization. The disease could be serologically proved in 4 patients and Legionella pneumophila SG1 was isolated from samples of 2 patients and from sediment of the hot-water tank. Since the opening of the hotel until the end of May, 19 hotel employees developed a febrile illness of short duration. The disease was serologically proved in 7 of them. The morbidity rate in tourists was 2.5%, while it amounted to 7.1% in the hotel employees. The epidemic lasted for 16 days. The infection spread through the hot water, and antiepidemic measures were limited to its pasteurization and hyperchloridation. The chain of infection was broken off by the application of those measures. PMID- 2233112 TI - [Computer-assisted teaching in medical education--development of methods and supplemental materials]. AB - A review of the elementary types of materials for the computer assisted learning (CAI--Computer Assisted Instruction) is given in this paper. It shows our initial experiences in creating the computer educational materials of the patient management simulation type, destinated for the primary care physicians. A computer simulation program "First Aid in Traffic Accident" is described as an example. A typical structure of these materials is shown. The materials had been developed using the own authoring system, a computer program which enables the teachers and other experts to create the computer educational materials independently, with the minimal help of the professional computer experts. PMID- 2233113 TI - [Is there a rheumatic fever?]. AB - In 1988, 11 patients with a suspicion to rheumatic fever (RF) or acute polyarthritis were admitted to the Department of Internal Medicine, University Hospital, "Dr. M. Stojanovic". Eight patients have been extensively treated together with a physiatrist, while one of them on an outpatient basis. Follow-up has been from 3 to 9 months. Rheumatic fever was diagnosed with a certainty in only one patient. Three have had the diagnoses of Reiter's syndrome and individually, of infectional, ankylosing and rheumatoid arthritis. One patient is still followed up because of the symptomatic diagnosis of partially cured oligoarthritis or recurrent RF. The numerical relation of established diagnoses for the followed up patients has been in accordance with the decrease in incidence of RF both in our country and the world some decades ago. The possible causes of frequent diagnoses of RF in adults and the necessity of careful evaluation of clinical and laboratory parameters and the need to follow-up unclear polyarthritis even when the patients are not hospitalized, until the definite diagnosis has not been made is stressed in this paper. Therefore, the administration of corticosteroids has to be avoided in these patients, except in special cases. PMID- 2233114 TI - [Intestinal pseudoobstruction in hypothyroidism]. AB - Just as gastrointestinal functional diseases affect the thyroid, so thyroid disfunction affects the structure and function of almost all parts of the gastrointestinal tract. Hypothyroidism has frequently been associated with various gastrointestinal manifestations, including constipation, bloating, flatulence, atrophic gastritis, ileus, atony and dilatation of the oesophagus, stomach, gallbladder, small intestine and colon. Characteristic intestinal hypomotility in a severe hypothyroidism may progress to intestinal pseudoobstruction, paralytic ileus and megacolon. These rare but potentially serious complications must be recognized and treated promptly with adequate doses of thyroid hormone replacement therapy. The case history of a 64-year-old woman with hypothyroidism and intestinal pseudoobstruction is described. PMID- 2233115 TI - [The effect of diltiazem and nifedipine in persons with essential hypertension]. AB - After a two-week placebo period, 40 patients were randomly divided into two groups in a six-week double blind parallel study. Group A received diltiazem (Cortiazem retard, Hemofarm) 90 mg twice daily and group B nifedipine 10 mg three times daily. Blood pressure and heart rate were measured at the end of weeks 2, 5 and 8 at rest, in the supine and standing positions and during ergometric exercise of 50, 75 and 100 wattes. Blood pressure at rest, in the supine position, decreased comparably in both groups. The response rate (reduction in diastolic blood pressure of at least 10 mmHg or less than or equal to 90 mmHg) was 83% in the diltiazem group and 80% in the nifedipine group. Exercise blood pressure was also comparable in both groups. Resting heart rate was unchanged in the diltiazem, whereas in the nifedipine group a tendency to increase was observed. The pressure rate product significantly decreased (p less than 0.05) in the diltiazem only in exercise of 100 W and increased slightly in the nifedipine group. There were two drop-outs in the nifedipine group due to side effects and none in the diltiazem group. PMID- 2233117 TI - [Mechanisms of epidermal growth factor activity]. AB - Epidermal growth factor is a Mr 6045 polypeptide which binds to its own cell surface receptor and stimulates its intrinsic tyrosine kinase activity. Activation of this signal transducing system is believed to be involved in many physiological and pathophysiological processes. Some aspects of these processes are discussed in this review. PMID- 2233116 TI - [Pathophysiology of atherosclerosis. II. Etiopathogenic mechanisms and risk factors]. AB - The authors present an up-to-date review on etiopathogenesis of atherosclerosis. Theories of etiology of atherosclerosis are described: response-to-injury hypothesis, lipid deposition hypothesis, lysosome hypothesis, encrustation hypothesis, mural thrombi hypothesis, monoclonal and clonal senescence hypothesis. The role of endothelial injury and platelet adhesion as well as smooth muscle cells proliferation due to these events, their growth control and the role of macrophages in atherogenesis are explained thoroughly. Special attention is focused on the interaction of arterial cells and lipoproteins at sites of vessel injury, lipid metabolism of the lesion and on synergy of arterial injury caused by various injury mechanisms and hypercholesterolemia in atherogenesis. Atherosclerotic risk factors and their impact on atherogenesis are discussed as well (e.g. hyperlipoproteinemia, hypertension, tobacco smoking, diabetes and abnormal glucose tolerance, gout, obesity, menopause and oral contraceptives, diminished physical activity, type A of personality behavior etc.). The possibilities of regression or reversal of ateromatous plaques are presented too. PMID- 2233118 TI - [Modern referral-information service in the Central Medical Library of the University of Zagreb Medical School]. AB - New technologies in information and retrieval services of the Central Medical Library are presented, as well as comparison between traditional search of biomedical literature and search of biomedical bases available on CD-ROM and on line. MeSH thesaurus represents the basis for all modes of searches, either through published indexes (Index Medicus, Biomedicina Iugoslavica), searches through on-line, or via CD-ROM technology. Experience in indexing according to MeSH structure helps us to search and retrieve biomedical literature on new media too. Great interest in new media for search and retrieval of biomedical literature among our users (100%) justifies their introduction into the Library. In the period of four months, 75% of our users chose CD-ROM technology in their search, 25% chose on-line search, and both technologies were combined by 33% of the users. Having these new media in our library we have reached the point from which we join the world biomedical information network and successfully meet the growing need for information in the field of biomedicine. PMID- 2233119 TI - [The work of Dr. Lavoslav Glesinger in the history of medicine (1901-1986)]. AB - In this paper special attention has been given to the analysis of the elements of the life and work of Professor Lavoslav Glesinger, M.D.,Ph.D., being at the same time the indicators of his role in the process of the development and recognition of the history of medicine as a profession and scientific, educational and academic discipline in our environment. With regard to the assigned object, all available bibliographic material has been studied. Professor Glesinger, being a physician practitioner, showed the interest in that field even in the period from 1931 to 1948 and wholly devoted himself to it working as a professional researcher and professor at the School of Medicine, University of Zagreb in the period from 1948 to 1976, and as a scientist at the Institute for History of Science, Mathematics and Medicine of the Yugoslav Academy of Arts and Sciences, Zagreb, in the period from 1960 to 1981. PMID- 2233120 TI - [A rational approach to the prevention and treatment of osteoporosis]. PMID- 2233121 TI - [Hypocritical humanism]. PMID- 2233122 TI - [Prevention of AIDS transmission]. PMID- 2233123 TI - Pentoxifylline inhibits lipopolysaccharide-induced serum tumor necrosis factor and mortality. AB - Tumor necrosis factor, a mononuclear phagocyte-derived peptide produced in response to lipopolysaccharide, has been shown to mediate certain aspects of septic shock and multiple organ failure resulting from gram-negative septicemia. In the present investigation, pretreatment of animals with pentoxifylline inhibited lipopolysaccharide-induced serum tumor necrosis factor in a dose dependent fashion. Pentoxifylline prevented the sequestration of neutrophils seen in animals given intravenous lipopolysaccharide. Furthermore, pentoxifylline protected animals from the lethal effects of an intravenous challenge with lipopolysaccharide. These data indicate that pentoxifylline inhibits lipopolysaccharide-induced tumor necrosis factor and may be an effective agent in mitigating the lethal consequences of sepsis and other disease processes mediated by this cytokine. PMID- 2233124 TI - Protective effect of human epidermal growth factor against the experimental gastric mucosal lesions in rats. AB - The protective effect of human epidermal growth factor (hEGF) on the gastric mucosal lesions in rats was examined in relation to the immunoreactive concentration of plasma. Human EGF (30 micrograms/kg) was administered intravenously, intraperitoneally or subcutaneously. At different times following the administration of hEGF, rats received acidified ethanol solution to induce an experimental gastric mucosal lesion. Sum of lesion length in the gastric mucosa was used as a lesion index. Human EGF administered parenterally markedly decreased the gastric mucosal lesions in 10 min after administration of necrotizing solution, and 10 to 30 min delay was observed in the development of maximal protective action. Profiles of protective potency against the hEGF dose administered intraperitoneally or subcutaneously 30 min before administration of necrotizing solution revealed that the effective dose of hEGF (ED50) was about 5.2 and 2.6 micrograms/kg, for intraperitoneal and subcutaneous administrations, respectively. PMID- 2233125 TI - Ethanol and diolein stimulate PKC translocation in astroglial cells. AB - Ethanol exposure stimulates taurine release from astroglial cells. To determine if ethanol mediates this release using protein kinase C (PKC), PKC activity was measured using LRM55 astroglial cells. When ethanol (25-200 mM) or diolein (3 microM) was applied to cells for 30 seconds, PKC activity was observed to decrease in the cytosol and increase in the membrane fraction of the cell while the whole cell activity remained unchanged. The membrane-associated activity increased by almost 100%. When ethanol (100 mM) and diolein (3 microM) were applied simultaneously, membrane-associated activity increased to become 3-5 times greater than when either PKC activator was applied alone. These changes in PKC activity parallel changes in taurine release observed when cells are exposed to ethanol and the PKC activator diolein. Ethanol-stimulated release may be associated with the translocation of PKC activity from the cytosol to the membrane. PMID- 2233126 TI - The role of acetate in alcohol-induced alterations of uterine glucose metabolism in the mouse during pregnancy. AB - The acute exposure of mice to ethanol during post-implantation pregnancy has been reported to cause alterations in the levels of several glycolytic intermediates in the uterus, suggesting a possible indirect mechanism of alcohol embryo toxicity. The present study was undertaken to assess whether the ethanol metabolite, acetate is implicated in this phenomenon. Blood and uterine alcohol concentrations in day 9--pregnant Quackenbush Swiss mice were maximal 15 minutes after the intraperitoneal injection of ethanol (3.5 g/kg body weight), and fell to almost negligible levels 6 hours later. In response to this treatment, the levels of blood and uterine acetate increased, liver glycogen decreased, plasma glucose increased, and uterine glucose, glucose-6-phosphate (G-6-P), fructose-6 phosphate (F-6-P), and citrate increased. When acetate was administered to pregnant mice in amounts approximating those generated by exposure to alcohol, the levels of uterine F-6-P and citrate increased while other metabolic parameters remained unaffected. The administration of 4-methylpyrazole to mice subsequently treated with alcohol produced conditions of alcohol exposure in the absence of ethanol-derived acetate and depressed the ethanol-induced rise in uterine G-6-P and citrate. The results support the notion that acetate contributes to the alcohol-induced alterations in metabolism, at least as far as the regulation of uterine citrate and hexose monophosphates are concerned. This, together with stress responses induced by exposure to the acute dose of alcohol, may present mechanisms underlying the fetal alcohol syndrome associated in particular with "binge" drinking. PMID- 2233127 TI - Lipid activators of protein kinase C. AB - Among the many reported lipid activators of protein kinase C only those of high affinity can be considered true physiological effectors, at present the tumor promoters, e.g., phorbol esters; 1,2-diacyl-sn-glycerols; and phosphatidylinositol 4,5-bisphosphate. Many other compounds (including arachidonic acid) are activators at high, unphysiological concentrations only, and they seem to be sterically unsuited for bonding to the enzyme. Such pseudo activators possibly act by scrambling the structure of the regulatory moiety of the kinase. PMID- 2233128 TI - Difference in the effects of the antidepressant tianeptine on dopaminergic metabolism in the prefrontal cortex and the nucleus accumbens of the rat. A voltammetric study. AB - The effects of the new tricyclic antidepressant tianeptine were investigated on dopaminergic (DAergic) metabolism in the anteromedian prefrontal cortex and the nucleus accumbens of the rat. DAergic metabolism was assessed by the measurement of DOPAC, the main presynaptic metabolite of dopamine, using in vivo voltammetry in rats ventilated with halothane (0.5-0.75% in air). Acute treatment with tianeptine (10 mg/kg, 20 mg/kg) only increased significantly DOPAC levels in the anteromedian prefrontal cortex. After chronic treatment with tianeptine (15 days, 2 times/day) the increases in DOPAC levels in this structure were altered and less pronounced with the 20 mg/kg dose. Previous studies led to suggest that both acute and chronic effects on DAergic terminals in the anteromedian prefrontal cortex may be involved in the therapeutic action of this new antidepressant. PMID- 2233130 TI - Effect of human epidermal growth factor (hEGF) on splanchnic circulation in dogs. AB - The effect of intravenous administration of human epidermal growth factor on the splanchnic blood flows was examined in anesthetized dogs, using an ultrasonic transit-time volume flow meter. Human epidermal growth factor (0.1, 0.5 and 1 microgram/kg) significantly increased blood flows in the portal vein (36.9 +/- 7.4% at 1 microgram/kg) and the superior mesenteric artery (49.0 +/- 16.8% at 1 microgram/kg). Systemic blood pressure monitored simultaneously was significantly decreased (8.4 +/- 1.2% at 1 microgram/kg). This study is the first to demonstrate that intravenous administration of epidermal growth factor increases the portal venous blood flow. PMID- 2233129 TI - Effect of cocaine and cocaine metabolites on cerebral arteries in vitro. AB - Cocaine has pronounced peripheral vasoconstrictor effects. Despite the short half life of cocaine in the body these effects are relatively long-lived. The role of cocaine metabolites in vasoconstriction attributed to cocaine has not been reported. We evaluated the contractile ability of cocaine and its major metabolites in isolated cat cerebral arteries. The primary cocaine metabolite, benzoylecgonine was a potent contractile agent, causing a 50% decrease in cross sectional area at 10(-5) M. This was less than caused by serotonin, but greater than caused by norepinehrine. Ecgonine and cocaine were less active contractile agents than was benzoylecgonine, and ecgonine methyl ester was a mild relaxant. PMID- 2233132 TI - Effects of cocaine and morphine on IgG production by human peripheral blood lymphocytes in vitro. AB - Elevated serum levels of IgG are amongst the immunological abnormalities exhibited by intravenous drug addicts. We therefore addressed the hypothesis that cocaine and morphine (the major metabolite of heroin) exert a direct effect on human B cell function in vitro. Human peripheral blood mononuclear cells from normal individuals were incubated for 7 days with the T cell-dependent B cell activator pokeweed mitogen (PWM) and serial dilutions of either cocaine or morphine. At the end of this time total IgG was measured by use of a sandwich ELISA incorporating a biotin-labelled affinity-purified anti-IgG and streptavidin peroxidase. At concentrations relevant to those found in plasma, morphine and cocaine did not affect PWM-stimulated IgG synthesis in vitro. We suggest that these drugs of abuse do not directly influence human B cells, but in vivo exert immune modulatory effects via indirect mechanisms. PMID- 2233131 TI - Affinity profile of the novel muscarinic antagonist, guanylpirenzepine. AB - The study reports the functional affinity of an amidino derivative of pirenzepine, guanylpirenzepine, for muscarinic receptors mediating relaxation of rat duodenum, inhibition of rabbit vas deferens twitch contraction (both receptors previously classified as M1), guinea pig negative inotropism (M2) and ileal contraction (M3). Unlike pirenzepine, guanylpirenzepine discriminated between duodenum and vas deferens receptors, with a 30-fold greater affinity for the former subtype. The unique selectivity pattern of guanylpirenzepine (duodenum greater than vas deferens greater than ileum greater than atrium) renders it a promising tool for the classification of muscarinic receptor subtypes. PMID- 2233134 TI - In vivo stereological assessment of caudate volume in man: effect of normal aging. AB - Using intermediate weighted magnetic resonance imaging (MRI) and a systematic sampling stereological method in 39 normal volunteers aged 24-79 years old, we demonstrated a marked age-associated decline in caudate nuclei volume (r = -0.69, p less than 0.0001). The mean absolute volume of the caudate nuclei in this study (9.4 cm3) was almost identical to that reported in a previous autopsy study and further confirms the validity of this stereological technique for use with MR images. This technique will provide a method for measuring the caudate and other nuclei in vivo, from brain images and, as such, a research tool to correlate age associated changes in cognitive, sensory and motor function with caudate nucleus volume and other brain regions. PMID- 2233133 TI - Effects of bile acids on actin polymerization in vitro. AB - Bile acids are major determinants of canalicular bile secretion, and there are indications that choleretic bile acids increase bile canalicular contractions, in isolated rat hepatocytes. Therefore, we examined the influence of various bile acids on the rate of actin polymerization in vitro. The free forms of cholic acid, ursodeoxycholic acid, and chenodeoxycholic acid, as well as their taurine and glycine conjugates, were incubated with purified muscle actin, at a concentration of 100-300 nmoles/mg actin. The rate of actin polymerization was measured by viscometry and the fluorescence of the pyrene probe, linked to actin. Results showed that all bile acids slow the rate of polymerization, and that the effect was dose-dependent. However, the reduction by chenodeoxycholic acid was greater than that caused by the other bile acids. The results indicate that bile acids, particularly in high concentrations interact with actin, a finding that may be related to the increased bile canalicular contractility, and altered canalicular membrane morphology, induced by choleretic bile acids. PMID- 2233135 TI - Effect of plasma from essential hypertensives on vascular tone of aortic strips, isolated perfused mesentery and isolated perfused kidney. AB - Different vascular models of normotensive Wistar rats, including aortic strips, isolated perfused mesentery and isolated perfused kidney, were used to study hemodynamic effects of plasma fractions obtained by gel filtration from the blood of essential hypertensive and normotensive subjects. Plasma fractions from essential hypertensives studied had been shown to increase blood pressure after intravenous injection in rats. In the aortic strips, 50 microliters of a hypertensive fraction (HF) elicited a calcium-dependent contraction of 0.14 +/- 0.035 mN (n = 20, p less than 0.05), which was inhibited by nifedipine, whereas tension of the strips was not significantly changed by normotensive fractions (NF) (n = 17). In the isolated perfused mesentery preparation, no significant change of perfusion pressure by HF or NF could be demonstrated (n = 10). In the isolated perfused kidney, a transient increase of perfusion pressure was induced by HF (19.5 +/- 16.6 mm Hg, n = 40, P less than 0.001) but not by NF. This increase was abolished in calcium-free, 2 mmol/l EGTA containing perfusion medium. The response was diminished, but not abolished by nifedipine. These data demonstrate vasopressor properties of plasma from essential hypertensives, which might be the consequence of a circulating vasoconstrictor substance in the blood of essential hypertensives. PMID- 2233136 TI - Leucocytes and pulmonary disorders: mobilization, activation and role in pathology. PMID- 2233137 TI - Current concepts in olfaction. AB - Because of the location of the olfactory epithelium and bulb, the processes involved in olfaction have been difficult to evaluate. However, the recent application of comprehensive nasal endoscopy, reproducible olfactory testing, and molecular biologic techniques to the study of the transduction of olfactory information has elucidated some of the events in odorant perception. PMID- 2233138 TI - The In Vitro Fertilization Program at the Greater Baltimore Medical Center. PMID- 2233139 TI - Pathogenic factors in the development of type I and type II diabetes mellitus: 1990. AB - The pathogenesis of IDDM and NIDDM indicates a distinct difference between these diseases. Viral illness is implicated in IDDM, linked with evidence for an immune deficiency. NIDDM is not linked to viral illness or autoimmunity but is highly influenced by the inheritance of a defect in insulin production. PMID- 2233140 TI - Cervical spondylosis: a therapeutic update. PMID- 2233141 TI - Role of the community hospital in cancer research. PMID- 2233142 TI - Evaluation of patients with claudication. PMID- 2233143 TI - The Physician Rehabilitation Program of the Medical and Chirurgical Faculty of Maryland: twelve years and going strong. PMID- 2233144 TI - The effect of physician impairment on the family. AB - There are few studies on the effect of physician impairment on the marriage and the family. There is a need for research on both the functional and non functional medical marriage, and treatment needs to be devised to focus on the special needs of the medical family. PMID- 2233145 TI - The role of the medical review officer in the workplace. AB - MROs need to be knowledgeable and experienced in the area of substance abuse. This relatively new field raises many clinical issues, complicated by legal and ethical issues. It is advisable that MROs be independent from the companies, laboratories, and collection sites with which they contract or to which they relate in the process of performing their evaluations. PMID- 2233146 TI - Physician addiction to pharmaceuticals: personal history, practice setting, access to drugs, and recovery. AB - Specialists in the field of anesthesiology, emergency medicine, and general or family practice are at increased risk of addiction. They may manifest a pattern of habitual overwork and/or grandiosity, have unrestricted access to drugs, and initiate use through self-medication. PMID- 2233147 TI - The Physician Rehabilitation Program of Maryland. AB - The Physician Rehabilitation Program of Maryland has been developed by Med Chi's Committee on Physician Rehabilitation over the last twelve years. Its primary purpose is to assist physicians who are experiencing problems because of substance abuse, physical disability, or psychiatric illness. Rapid changes in the field have challenged the Committee in recent years. New funding which started in July of 1990 will assist Med Chi in meeting these new challenges. PMID- 2233148 TI - Venomous snakebites. PMID- 2233149 TI - Near-drowning accidents among children. PMID- 2233150 TI - Sunlight, ultraviolet radiation, and the skin excerpts: NIH consensus statement. PMID- 2233151 TI - Thoracic spine schwannoma: the role of Gd-DTPA enhanced MRI. PMID- 2233152 TI - Centralized credentialing: state-of-the-art confidential clearinghouse. PMID- 2233153 TI - The duty to warn: the present law. PMID- 2233154 TI - Morality and sex: BPQA decisions. PMID- 2233155 TI - Sequential decision making with continuous disease states and measurements: I. Theory. AB - The question of whether to perform a continuous valued test to assess a continuous valued health state such as blood pressure or serum cholesterol is explored by decision analysis. Principal assumptions are that the underlying health state and measurement variability are both normally distributed, and that the impact of treatment on the utility of outcomes varies linearly with the underlying health state. Using Bayes' theorem, an expression for the expected utility of performing the test is derived and compared with immediate treatment or decision to withhold treatment. The calculations can be carried out with a pocket calculator and a table of the normal distribution. Iterating the analysis, a sequential decision making process is developed, leading to a series of no treat/test again and test again/treat thresholds with which a running average of independently obtained measurements can be compared to produce stepwise optimal results. The thresholds are readily calculated on a microcomputer. Finally, the conjugate-normal-linear model is extended to encompass the correlated observations that may be made on a single visit. This paper concentrates on the mathematics of decision making with continuous variables. The companion paper illustrates its application to diastolic blood pressure. PMID- 2233156 TI - Sequential decision making with continuous disease states and measurements: II. Application to diastolic blood pressure. AB - The model and strategy for sequential decision making using normally distributed measurements proposed in a companion paper are applied to the problem of diagnosing diastolic hypertension. The assumptions of the model are discussed and justified clinically. Methods for assigning values to the model's parameters are explained and illustrated in the context of a hypothetical "generic" patient. Although current national recommendations and the sequential strategy both lead to an average of 1.89 measurements per patient prior to diagnosis, the sequential strategy applies a sequence of four or more measurements to 12% of patients. Fewer than 1% of patients would require ten or more measurements under this strategy. The sequential strategy leads to fewer patients' receiving unnecessary treatment and substantially higher expected utility for the patient. The role of multiple blood pressure determinations per visit is explored in the absence of appropriate estimates. Even under "best-case" assumptions, however, it is shown that obtaining more than one observation per visit is called for only in about 15% of visits. While the exact role of multiple determinations cannot be specified from existing data, it is likely to be much more limited than current recommendations suggest. PMID- 2233157 TI - Improvement of decisions regarding hemodialysis patients by urea kinetic modeling. AB - The potentials for improving decisions about adequacy of dialysis (AD) and daily protein intake (DPI) by urea kinetic modeling (UKM) were examined. Four nephrologists evaluated AD, DPI, and metabolic stability in 62 patients. UKM was done three times; but the results were not revealed. Clinicians' decisions were then compared with UKM measures of effective dialysis (Kt/V) and protein catabolic rate (pcr). Detection of inadequately treated patients by the clinicians was poor (28%, Kt/V less than 1.0; and 40%, Kt/V less than 0.9). Specificities of the clinicians' decisions were 0.96 and 0.92, respectively. Combining pcr and consensus decisions, 59 patients could be assigned a probable DPI. Using this as "gold standard," the average clinician detected 77% of 13 low DPIs. Single or triple pcr determinations alone detected 77% or 62%, respectively. Specificities were 0.91, 0.85, and 1.0. Simulated decision making suggested that combining pcr with clinical evaluation in a logical way would lead to detection of most patients with low DPI. Qualitative data from individual patient cases causing controversies are presented and discussed. It is concluded the UKM should be used routinely to assess the adequacy of dialysis and daily protein intake. PMID- 2233158 TI - Determining a range of false-positive rates for which ROC curves differ. AB - Many indices have been proposed for summarizing the information contained in the ROC curve. When comparing two ROC curves, though, there are times when global summary measures are either not optimal or not appropriate. The author presents a method for directly comparing true-positive rates for two diagnostic, screening or prognostic tools, determining over what range of false-positive values the tests differ. The method is applicable for independent or dependent samples. An example concerning gallium citrate imaging is presented, as well as an example using a prognostic index for severity of illness in the ICU. The range of false positive rates for which the ROC curves differ is determined for each example. PMID- 2233159 TI - Twisted sisters: when is the optimal tme for delivery? PMID- 2233160 TI - Recent developments in medical decision making. PMID- 2233161 TI - [The physicotechnical support of radiation diagnosis and therapy]. PMID- 2233162 TI - [The problems of medical radiobiology]. PMID- 2233163 TI - [The basic problems of radionuclide diagnosis in the USSR]. PMID- 2233164 TI - [The suspicion of obstructive jaundice]. PMID- 2233165 TI - [The use of Gruntzig-type balloon catheters for dilatation in stenoses of the pylorus and the duodenum]. AB - The paper is concerned with original methods of balloon dilatation with high pressure low-profile balloon catheters of Gruntzig type of pyloric and duodenal stenoses. A new informative method of recording of this procedure and its results with computer for radiography was described. In 10 patients this method was used alone as well as in combination with sparing operation--selective proximal vagotomy. In 80% of cases a positive effect of this procedure was obtained and confirmed by clinical observation and instrumental methods. No complications were noted. Therefore this methods could be recommended for a wider clinical use. PMID- 2233166 TI - [The All-Union Congresses of Roentgenologists and Radiologists]. PMID- 2233167 TI - The interplay of culture and symptoms: menstrual symptoms among Samoans. AB - Menstrual symptomatology has received much attention in recent years but little attention has been given to the interplay of culture with these symptoms. Interview data from male and female Samoans in rural Western Samoa, rapidly modernizing American Samoa, and modern Hawaii are used to explore the role of culture and culture change in explaining variations in reports of menstrual symptomatology and menstrual distress. I suggest that culture plays a significant role in the recognition, evaluation, and expression of menstrual symptoms, and thus culture must be considered along with biological and psychosocial variables in the evaluation of symptomatological differences, including differences in number and kind. PMID- 2233168 TI - Chiropractors for and against vaccines. AB - The publications of philosophically conservative chiropractors document their allegiance to a posture of hostile opposition to health prevention based upon immunization procedures. The challenge to medical anthropology is to make sense of what seems scientifically senseless. This paper attempts to come to an understanding of this position by tracing professional attitudes which are derived from a history of political and economic conflict with the American medical establishment, which emanate from an explanatory model of disease causation that preserves a nineteenth century monocausal theory, and which reflect a process of cultural schizmogenesis. In preserving these heretical medical beliefs, conservative chiropractors, who are trained in the basic medical sciences, defend themselves by basing their opposition to immunization upon imperfections in vaccines that relate to the efficacy, safety and necessity of immunizations. Further, they persist in a belief that chiropractic spinal manipulation provides an alternative method for achieving immune status. This belief has not been subjected to testing in clinical trials or laboratory experiments, and thus becomes a matter of belief rather than of scientific verity. A refusal to advocate or submit to vaccines serves conservative chiropractors as an understandable cultural symbol, but it is a symbol with sinister health costs to those who translate it into non-immune status in a world otherwise still hostage to disease-producing organisms. PMID- 2233169 TI - Navajo childbirth in transition. AB - For the Navajo Indians, the transition from home-centered childbearing practices based on religious ritual to biomedically directed childbirth in hospitals was completed over a relatively short time in the middle decades of this century. For Anglo-American society, the acceptance of medically oriented childbirth occurred during an equally short period earlier in the century. The transition was driven for both by many common factors. For Navajo women it was additionally influenced by the social and economic changes that affected the Reservation following the beginning of the Second World War. This paper examines the changes in Navajo childbearing practices and, for comparison, those of the dominant American society. It reviews factors that permitted the acceptance of biomedical childbirth by Navajo women and explores the health implications of the transition. PMID- 2233171 TI - Migration, changing gender roles and stress: the Samoan case. AB - The impact of migration and social change on male and female role expectations is examined in an urban Samoan community. Expanding role expectations and role conflicts in the urban context are linked to differential experiences of stress by gender, which are in turn examined with respect to the health outcomes of arterial pressure, a measure of physical health status, and a psychosomatic complaint index. PMID- 2233170 TI - The forty-day rest period and infant feeding practices among Negev Bedouin Arab women in Israel. AB - Four hundred and twelve Bedouin Arab women were interviewed within 48 hours of delivering a newborn in 1982 and two months later to examine the effect of social support during the forty-day postpartum rest period on the incidence of exclusive breast feeding at two months. Whereas the distribution of infant feeding practices at two months did not differ among women with and without support during the "forty days," the number of days of help during the "forty days" was significantly associated with type of feeding at two months. The longer the duration of help, the greater were the odds of maintaining exclusive breast feeding after adjustment for covariates by multinomial logistic regression analysis. The association between duration of help and infant feeding practices at two months was modified by the interview month and the feeding practices of the respondents' primary social supports. More respondents with infants who reached two months of age in May and June were exclusively breast feeding than respondents with infants who reached two months in the hot, dry months of July and August. Also, respondents with sisters-in-law who breast fed alone or in combination with the bottle were feeding their infants in the same way after adjustment for covariates. Given the beneficial effects of breast feeding on infant health and development, these findings identify potential avenues of intervention for programs promoting breast feeding. PMID- 2233172 TI - Order and healing: the concept of order and its importance in the conceptualization of healing. AB - This paper concerns the notion of order and its role in the conceptualization of healing, and therefore its importance to healing itself. It proposes a model of healing in which order is central. The paper begins with an example drawn from Javanese mystical practices which are based upon the concept of the unity of the human and natural orders. The Javanese case provides a metaphor for an expanded notion of order. This prefigures a consideration of the nature of the concept of order in medical anthropology, science, and medicine. The importance of the notion of analogy (and metaphor) in the concept of order and how order may be simultaneously conceptualized in both cognitive and biological domains is also discussed in the paper. The perspective on order and healing developed here goes beyond conventional biomedical categories and provides a basis for the fundamental reconceptualizations necessary for addressing contemporary developments in psychoneuroimmunology, for example. PMID- 2233173 TI - Falling through the cracks: contradictions and barriers to care in a prenatal clinic. AB - Prenatal care is often cited as a major factor in the prevention of poor birth outcomes. Yet, the social environment of care has been little studied. This paper illustrates how contradictory features in the structure of the health care system create barriers that weaken effective health care delivery. Social relations in a large urban public outpatient clinic are described and analyzed regarding their impact on clinic procedures. The paper focuses on: 1) the division of labor in which work is compartmentalized and power is diffused; 2) the asymmetrical doctor patient relationship magnified by social class differences; and 3) the training of resident physicians who provide primary prenatal care. Improvements in the quality of care in public clinics cannot come about without an understanding of the effects that contributing factors have on the way care is organized. PMID- 2233174 TI - Postmodernism and medical anthropology: words of caution. AB - Of late, discourse in anthropology increasingly has been set within the frame of postmodernism. While debate continues as to whether postmodernism represents a particular period or an historically conditioned perspective (or interrelated set of perspectives) within the social sciences and beyond, it is clear that assessment is needed of the impact of postmodernism on work within the field. This paper represents a critique of the potential effect of postmodernism within medical anthropology. It is the argument of this paper that despite the postmodern eschewal of so-called grand theory, postmodern writers in anthropology smuggle a theoretical perspective into their work. The problems of this perspective in terms of the critical turn within medical anthropology are examined. PMID- 2233175 TI - Doctoring as business: a study of entrepreneurial medicine in Nigeria. AB - Medicine is often regarded as a philanthropic science in the service of humanity. Rather than universalistic humanitarian service (a la Hippocrates), this study of private practice illustrates that medicine has been commoditised and is now a lucrative business much like the sale of beer and other commodities. This growing medical enterprise is explained against the backdrop of the wider dynamics of the Nigerian political economy. The implications of this growing privatisation and commercialisation, of which the doctoring business is a part, are examined. It is concluded that it is only a question of time before entrepreneurial medicine completely eclipses the beleaguered public medical system. PMID- 2233176 TI - Access to traditional medicine in a western Canadian city. AB - This paper examines the question of access to traditional Indian medical systems in the western Canadian city of Saskatoon. The data demonstrate that many Natives desire such access, and do not see difficulties in having Indian healers available in Western-style biomedical clinics. A variety of language variables proved to be the best predictors of access questions, indicating that those with the greatest cultural adherence were most likely to want a more formal access. It is argued that a lack of access to traditional Indian medical services represents a legitimate health need. Considerations for the implementation of such a formal access to traditional Indian medicine are discussed. PMID- 2233177 TI - Rewarding medical teaching excellence in a major Canadian teaching hospital. AB - A major Canadian teaching hospital has developed a program to recognize and reward excellence in medical education. The program includes a system to collect and evaluate feedback from trainees and administrators--with an annual celebration event where awards are presented. Three categories of hospital-wide awards are presented: educational administration, program development, and extraordinary contribution. There are departmental awards for best undergraduate and postgraduate physicians, allied health professional, and house staff/fellow. This program functioned well to evaluate teachers across departments and for all levels of trainees in the hospital and will expand to become part of the ongoing evaluation of teachers in the institution. PMID- 2233178 TI - Teaching physicians about teaching: an experiential workshop. AB - Teaching improvement workshops are most effective when they engage teachers actively in practice teaching, particularly when the teaching situation is similar to the actual one to which the teachers will return. Teachers, however, often find such involvement threatening. In this paper we describe a 3 h workshop which succeeds in overcoming teachers' reluctance to participate in situations that are relevant to their real teaching problems, students, and subject matter. The most exciting outcome, in our view, was teachers' increased sensitivity to the limitations of their teaching approach and their increased awareness of the role of their concept of teaching in shaping their teaching strategies. Weaknesses of the workshop include its dependence on the skills of a group director, the tendency of the group to seek a single right answer instead of exploring alternatives and the usual danger of role rigidity which troubles all role enactment procedures. PMID- 2233179 TI - Teaching the teachers at Leicester: the general practice approach. AB - This article describes a systematic induction programme devised for newly appointed lecturers in general practice. The programme aims to help them develop skills in both teaching and assessment and to encourage self-appraisal. The progress of participants is monitored by direct observation and video-recording with the regular provision of feedback a prominent characteristic. All the lecturers have found participation in the programme an effective way of developing their teaching capabilities. PMID- 2233180 TI - Training managers for primary health care: teaching about community involvement. AB - Community involvement is a key element of the Primary Health Care (PHC) approach, and thus an essential topic on a course for managers of Primary Health Care programmes. This paper describes the teaching approach adopted on the Management for Primary Health Care course-a 3-month programme for PHC managers from developing countries, offered by the Liverpool School of Tropical Medicine, which attempts to overcome the difficulty of discussing this subject without a common reference point. Following a series of visits to community organizations in Liverpool, participants analyse factors which have influenced the formation and operation of these groups. Whilst preparing a report on key issues facing the community groups, and developing an analytic framework based on the Liverpool experience, participants are encouraged to draw parallels with their own working situation. Several advantages of this approach have been identified in the paper, but course organizers will have to balance these potential benefits with the investment of time and resources required to make it a success. PMID- 2233181 TI - Development of competence in clerkship. AB - Students' perceptions of their educational experience on Surgery and Medicine rotations of a clerkship program were analysed. Six components of the education process, namely (1) frequency of individual teaching, (2) quality of contact with staff-clinicians, (3) appropriateness of responsibility for patient care, (4) appropriateness of supervision received, (5) frequency of admissions reviewed and (6) frequency of opportunity to follow-up patients admitted, were correlated with students' confidence in their ability to function competently. Mean scores of clerks' confidence in their competence was the same for both rotations. Breakdown by sex revealed females to feel more competent on medicine, and males on surgery. On the medicine rotation a moderate relationship was found between two of the components tested and the dependent variable; on surgery, strong correlations were found between four of the components tested and the dependent variable. Regression analysis demonstrated appropriateness of responsibility for patient care to have a low predictor value for achievement of competence on medicine, while quality of contact with staff-clinician and appropriateness of supervision received were strong predictors of achievement of competence on the surgery rotation. PMID- 2233182 TI - Role play for the clinical tutor: towards problem-based learning. AB - A method of helping students learn paediatrics was developed utilizing role play as a stimulus to problem-based learning to arrive at a diagnosis. The tutor briefly stated a common paediatric problem and then took on the role of the patient and/or child, allowing himself to be interviewed by students working co operatively in a group. This process was interrupted by the students to discuss their progress and to determine what further information was required. A suitable patient was available to be examined if requested by the students. Although there was an initial tendency on the part of students to regard the exercise as 'unreal', they delighted in refining their communication skills and trying out their skills in problem solving. The tutor had to adopt a non-traditional role, as he was not directing the students or interrupting, so as to 'teach' the students more efficient information-gathering techniques or to correct any error made. The students were able to define and complete set tasks which they derived out of the session. The introduction of this technique encourages independent learning and the acquisition of problem-solving skills, and the students enthusiastically accepted this novel way of learning. The ready availability and versatility of the tutor allowed him to be used as the principal resource, and did away with the need for (and the additional expense of) specially constructed problem-based learning units, often unavailable in most departments. The method is described in detail so that other clinical tutors may feel encouraged to adopt a similar strategy. PMID- 2233183 TI - The surgeon simulator. AB - A new technique of small group surgical teaching has been developed wherein the surgeon takes on the role of the patient. This technique, which incorporates extensive and immediate formative evaluation, has all the advantages of simulation techniques while avoiding the major problems of training, scheduling and cost. This method has been used to teach a wide variety of surgical disease processes with the major emphasis being teaching patient management strategies. Sixty-one medical students have been taught using this method and they have found it superior to conventional seminar teaching, particularly in the domains of problem solving, patient management strategies and thought provocation. PMID- 2233184 TI - Effectiveness of an independent sexology course for Colombian medical students. AB - The outcome of an independent sexology course for Colombian medical students was evaluated by means of the Sex Knowledge and Attitude Test (SKAT), stressing the 'material' or 'substantial', rather than statistical, significance of changes after instruction. The results indicate that the course was as effective in producing increases in the students' sexual knowledge as previous non-independent courses, and as effective as them, or more, in modifying positively the students' sexual attitudes. These results are at variance with those of most sex education programmes described so far in the literature, whose effectiveness is in doubt due to the small magnitude of changes after instruction. PMID- 2233185 TI - What is ... a study guide? PMID- 2233186 TI - Community health staff's prejudice and knowledge about AIDS. AB - Health service workers' attitudes to their patients carry significant health care consequences. In order to investigate the relationships between health workers' attitudes to groups at high risk of AIDS and their knowledge of the disease and views on procedures for care, community health care workers and students completed a social distance questionnaire concerning groups defined by ethnicity, sexual proclivity, or illness. There was strong negativity towards individuals of minority sexual proclivity and AIDS high risk groups. Fear of the disease and ignorance of its transmission and effective care procedures increase with prejudice towards these groups. Analysis of their relevant prior learning experiences demonstrates the need for an educational programme which addresses the identified sources of ignorance and which also necessarily concentrates on the prejudices which serve as a barrier to effective patient care. PMID- 2233187 TI - The influence of laboratory experimental work on concept acquisition in a medical physiology course with implications for curriculum deliberations and instructional design. AB - Following revision of the curriculum the effectiveness of a traditional cookbook experiment, used in conjunction with an 'interpretation seminar', was evaluated. Curriculum revision had been predominantly concerned with an avoidance of overloading and provision of self-study periods. The preceding lectures were integrated with the experiment. The learning resulting from the practical experience was assessed using pre- and post-tests. The practical exercise was ineffective and did not facilitate conceptual understanding. Due to the central role of passive teaching methods the students adopted a surface approach to all learning, were teacher dependent and did not make effective use of their private study. Furthermore, owing to a broad-based entry into medical school many students lacked the basic skills essential to the achievement of meaningful learning. Clearly, for effective learning the curriculum and pedagogy must be geared to the background and educational needs of the students. PMID- 2233188 TI - Regulating patient flow for educational benefit in the pediatric teaching clinic: promoting learning through telephoned reminders. AB - As trends in medical care delivery shift from the inpatient to the outpatient setting, it is important that practices in medical education adapt accordingly. The environment of the teaching clinic should be warm, considerate of the needs of students, faculty, patients and their parents, and should allow ample time for discussion and independent learning. It may be difficult to cultivate such an environment in a medical school setting, if patient flow is uncontrolled. We piloted a simple program of telephone reminders for parents of children with appointments. Telephone reminders increased appointment compliance and improved the educational process. PMID- 2233189 TI - The child study: a multipurpose practical project in behavioural science. AB - This paper describes a behavioural science practical project suitable for preclinical medical students, in the form of a child study. The practical has low costs yet offers multiple benefits to students, including (a) first-hand exploration of the concepts of psychosocial development, (b) encouragement of self-directed learning and appraisal of research methodology, and (c) teaching and assessment of communication skills. PMID- 2233190 TI - J.B. Wolffe memorial lecture. Biomechanics: a bridge builder among the sport sciences. PMID- 2233191 TI - Bone mineral content of cyclically menstruating female resistance and endurance trained athletes. AB - The bone mineral content (BMC) at four sites on the axial and appendicular skeleton was compared among four groups of young adult (age = 17-38 yr) cyclically menstruating athletes (N = 40) who regularly performed either weightlifting resistance exercise (body builders) or nonresistance endurance exercise (runners, swimmers) and an inactive group of females (N = 18) of about equal age. Forearm BMC was measured using single photon absorptiometry at proximal (shaft) and distal sites on the radius. Dual photon absorptiometry was used to measure BMC at the lumbar vertebrae (L2-4) and femur at the femoral neck, Ward's triangle, and greater trochanter. Fat-free body mass (FFBM) was estimated from densitometry. Body builders had greater BMC than swimmers, collegiate runners, recreational runners, and controls. Mean differences in BMC among runners, swimmers, and controls were not significant (P less than or equal to 0.05). FFBM was correlated significantly with BMC (r = 0.35-0.56) at each site in the combined group of athletes (N = 39), whereas total body weight and BMC were correlated significantly at the distal radius site (r = 0.38) only. The results suggest that weight training may provide a better stimulus for increasing BMC than run and swim training. PMID- 2233192 TI - Variation in bone mineral content and estimated body fat in young adult females. AB - This study was designed to determine whether variability in bone mineral content (BMC) at the lumbar vertebrae (L2-4), radius shaft (RS), femoral neck, and distal radius can significantly contribute to the variability observed in body density (Db) among 89 females (age = 25.1 +/- 5.3 yr) of varying activity levels and menstrual status. Theoretical differences in Db were calculated at +/- 1 and +/- 2 standard deviations of BMC (SDBMC) for the population as well as for the subgroups: eumenorrheic inactive controls (C), recreational runners (RR), collegiate runners (CR), body builders (BB), swimmers (S), and amenorrheic runners (AR). Multiple regression to predict Db yielded significant coefficients (b) for BMC at L2-4 (b = 0.0190, P less than 0.001) and RS (b = 0.0425, P less than 0.01) when added separately to the sum of four skinfolds (subscapula, abdomen, thigh, calf). The differences in % BFHW at +/- 1 and +/- 2 SDBMC for the sample mean for RSBMC were +/- 1.0% and +/- 2.0%, respectively. Variability in L2 4 contributed differences of +/- 1.3% and +/- 2.6% at +/- 1 and +/- 2 SDBMC. The subgroup % BFHW differences (due to L2-4 and RS combined) ranged from an average overestimation of 1.3% for the AR to an average underestimation of 1.4% for the BB. Estimated mean errors for remaining groups were less than or equal to 0.5%. Individual differences ranged from a 3.3% underestimation (BB) to a 3.0% overestimation (AR).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233193 TI - Bone density in eumenorrheic female college athletes. AB - Information is limited on the effect of exercise on bone density in young eumenorrheic athletes. We studied 12 Caucasian intercollegiate volleyball players (V), nine basketball players (B), ten swimmers (S), and 13 non-athletes (N) with bone density measurements by photon absorptiometry of their calcaneus and lumbar spine (L2-L4). The effect of athletic status on bone density was analyzed by multivariate analysis of covariance, with height and weight as covariates. The bone densities reported below are mean +/- SE, adjusted for the covariates; units = g.cm-2, P less than 0.005. The swimmers had a significantly lower mean density in the lumbar spine than all other groups; the non-athletes' mean density was also lower than that of volleyball players (V = 1.31 +/- 0.03, B = 1.26 +/- 0.04, N = 1.18 +/- 0.03, S = 1.05 +/- 0.03). The volleyball and basketball players' mean calcaneal densities were greater than those of the swimmers and non-athletes (V = 0.530 +/- 0.017, B = 0.564 +/- 0.023, N = 0.438 +/- 0.018, S = 0.375 +/- 0.019). The higher bone densities for athletes in vertical weight-bearing activities are consistent with some but not all published data. The swimmers' low bone density in the lumbar spine, less than published values for amenorrheic runners, was unexpected. PMID- 2233194 TI - Effects of menstrual phase and amenorrhea on exercise performance in runners. AB - There are few well controlled studies in terms of subject selection, menstrual classification, and exercise protocol that have examined both maximal and submaximal exercise responses during different phases of the menstrual cycle in eumenorrheic runners and compared these runners to amenorrheic runners. Thus, the purpose of this study was to measure selected physiological and metabolic responses to maximal and submaximal exercise during two phases of the menstrual cycle in eumenorrheic runners and amenorrheic runners. Eight eumenorrheic runners (29.0 +/- 4.2 yr) and eight amenorrheic runners (24.5 +/- 5.7 yr) matched for physical, gynecological, and training characteristics were studied. The eumenorrheic runners performed one maximal and one submaximal (40 min at 80% VO2max) treadmill run during both the early follicular (days 2-4) and midluteal (6-8 d from LH surge) phases. The amenorrheic runners performed one maximal and one submaximal (40 min at 80% VO2max) treadmill run. Cycle phases were documented by urinary luteinizing hormone and progesterone assays and by plasma estradiol and progesterone assays. No differences were observed in oxygen uptake, minute ventilation, heart rate, respiratory exchange ratio, rating of perceived exertion, time to fatigue (maximal), and plasma lactate (following the maximal and submaximal exercise tests) between the follicular and luteal phases in the eumenorrheic runners and the amenorrheic runners. We conclude that neither menstrual phase (follicular vs luteal) nor menstrual status (eumenorrheic vs amenorrheic) alters or limits exercise performance in female athletes. PMID- 2233195 TI - Plasma volume and renal function during and after ultramarathon running. AB - Plasma volume (PV) and renal function were studied in eight subjects for 3 d prior to and 6 d after a 56 km footrace. Immediately following the race, PV, creatinine clearance, and urine flow were unchanged from pre-race values. Over the subsequent 3 d, PV increased due initially to a 17 g influx of serum albumin and an associated increase in plasma sodium content, which persisted throughout the study period. A reduction in urine sodium secretion occurred during the race day. Creatinine clearance increased after the race and remained elevated for 48 h. Increases serum enzyme activities, C-reactive protein concentration, serum uric acid content, and plasma creatinine concentration and production suggest muscle damage. We suggested the following. First, the persistent post-exercise plasma volume expansion is initiated by an influx of albumin into the intravascular space with an associated increase in plasma sodium content. A decrease in urine sodium excretion during the race day would contribute to the latter. Second, the interpretation of post-race changes in serum constituents must take account of changes in plasma volume. Third, there is an increase in creatinine clearance, indicating an increase in glomerular filtration rate, after both standard and ultramarathon running. This may be caused by the products of muscle cell damage although the physiologic mechanism for this is unclear. PMID- 2233196 TI - Immediate and delayed effects of marathon running on lipids and lipoproteins in women. AB - The purpose of this investigation was to examine the immediate and delayed effects of prolonged strenuous exercise on plasma lipid and lipoprotein concentrations in female runners. Venous blood samples were collected from 12 female runners 24 h before, 10 min after, and 1, 3, and 5 d after running a 42 km marathon. Whole blood was analyzed for hematocrit and hemoglobin to determine plasma volume shifts. Plasma aliquots were assayed for total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglyceride concentrations, while low-density lipoprotein cholesterol (LDL-C) was estimated. Total cholesterol concentrations were significantly reduced 1 d following the exercise and were still lower 3 and 5 d post-marathon. LDL-C was lower immediately and 1 d after the marathon. HDL-C concentrations, corrected for changes in plasma volume, were elevated 24 h post-exercise. The ratio of HDL/total cholesterol was increased 24 h post-exercise. Triglyceride concentrations were elevated immediately following the marathon but returned to baseline levels by 24 h post-exercise. These results demonstrate that prolonged strenuous exercise in women produces changes in blood lipid profiles that can last for several days. PMID- 2233197 TI - Effects of exercise mode on muscle glycogen restorage during repeated days of exercise. AB - The purpose of this study was to examine differences in muscle glycogen storage during three successive days of running or cycling. In a crossover design, seven male subjects performed two 3-d trials of either running (trial R) or cycling (trial C) for 60 min at 75% VO2max. Biopsy samples were obtained before and after each day's exercise from the gastrocnemius (trial R) or vastus lateralis (trial C) muscle. Diets in the 2 d preceding and during each trial contained 5 g carbohydrate.kg-1.d-1 and 14,475 +/- 402 kJ.d-1. Mean pre-exercise glycogen content (mmol.kg-1 wet wt.) was significantly reduced in both trials on day 3 (103.4 +/- 6.0) when compared to day 1 and day 2 (119.9 +/- 6.8 and 116.4 +/- 5.7, respectively). Day 1 glycogen reduction was significantly greater in trial C (P less than 0.03), and glycogen restorage was greater (P less than 0.02) only in trial C between the 1st and 2nd d. On day 3, spectrophotometric analysis of PAS strains showed that pre-exercise glycogen content in either muscle group was significantly (P less than 0.01) less in Type I as compared to Type II fibers. This difference in fiber glycogen storage did not appear to be attributable to muscle damage as negligible leukocyte infiltration and low blood CK levels were obtained. No difference between modes were observed for CK values throughout the trials. These data suggest that the depressed glycogen storage before the 3rd d of exercise was due to the moderate carbohydrate intake. PMID- 2233198 TI - Changes in the protein nutritional status of adolescent wrestlers. AB - The protein nutritional status of adolescent wrestlers was studied to determine whether changes occur during a season of competition and weight loss. Subjects (N = 18) were measured prior to the start of the season (PRE), twice in the midseason, and once during late season (LATE) for weight, percent body fat, and height. At each of these times, a venous blood sample was obtained from the subjects, who were fasted, and analyzed for concentrations of albumin, prealbumin, retinol binding protein (RBP), blood urea nitrogen (BUN), hemoglobin, hematocrit, and 23 amino acids. Diet records were kept by subjects to assess daily energy, protein, fat, and carbohydrate intake. Data were analyzed by repeated measures ANOVA. Results showed that wrestlers decreased weight by an average of 6.6 +/- 0.9% and that percent body fat, fat-free weight, plasma levels of prealbumin and RBP, the ratio of total essential amino acids to total amino acids, and dietary energy nutrient intakes were significantly lower at LATE compared to PRE. RBP decreased during midseason and averaged (+/- SE) 3.21 +/- 0.15 mg.100 ml-1 at LATE; prealbumin was significantly lower at LATE with a mean value of 19.8 +/- 1.0 mg.100 ml-1. Total energy intake decreased from PRE values by 35%, to approximately 27 kcal.kg-1.d-1 during the season. In conclusion, in these high school wrestlers who lost approximately 6.6% of weight, there were adverse effects on some of the indices of protein nutritional status. PMID- 2233199 TI - Strength training effects in prepubescent boys. AB - Possible changes in muscle size and function due to resistance training were examined in prepubertal boys. Thirteen boys (9-11 yr) volunteered for each of the training and control groups. Progressive resistance training was performed three times weekly for 20 wk. Measurements consisted of the following: 1 repetition maximum (RM) bench press and leg press; maximal voluntary isometric and isokinetic elbow flexion and knee extension strength; evoked isometric contractile properties of the right elbow flexors and knee extensors; muscle cross-sectional area (CSA) by computerized tomography at the mid-right upper arm and thigh; and motor unit activation (MUA) by the interpolated twitch procedure. Training significantly increased 1 RM bench press (35%) and leg press (22%), isometric elbow flexion (37%) and knee extension strength (25% and 13% at 90 degrees and 120 degrees, respectively), isokinetic elbow flexion (26%) and knee extension (21%) strength, and evoked twitch torque of the elbow flexors (30%) and knee extensors (30%). There were no significant effects of training on the time related contractile properties (time to peak torque, half-relaxation time), CSA, or %MUA of the elbow flexors or knee extensors. There was, however, a trend toward increased MUA for the elbow flexors and knee extensors in the trained group. Strength gains were independent of changes in muscle CSA, and the increases in twitch torque suggest possible adaptations in muscle excitation contraction coupling. Improved motor skill coordination (especially during the early phase of training), a tendency toward increased MUA, and other undetermined neurological adaptations, including better coordination of the involved muscle groups, are likely the major determinants of the strength gains in this study. PMID- 2233200 TI - The influence of exercise intensity on heat acclimation in trained subjects. AB - Low-intensity exercise (less than or equal to 50% VO2max) has been demonstrated to produce heat acclimation (HA) in trained subjects. The purpose of this study was to determine whether shorter-duration, moderate-intensity exercise would also result in HA. Nine trained runners performed two 9-d exercise heat-stress protocols. Each protocol consisted of a 90-min heat tolerance test on days 1 (HTT1) and 9 (HTT2). On days 2-8 the subjects exercised at 50% VO2max for 60 min.d-1 (T50) or at 75% VO2max for 30-35 min.d-1 (T75). Final HTT2 heart rate and rectal temperature (Tr) were significantly (P less than 0.001) reduced, as compared to HTT1, with no differences between T50 and T75. Both protocols resulted in significant (P less than 0.05) reductions in HTT2 pre-exercise Tr and total exercising caloric expenditure, both of which are known to contribute to HA. No changes in resting plasma volume, osmolality, protein, post-HTT aldosterone, and exercising sweat rate were observed. These results demonstrate that equal levels of HA were obtained with T50 and T75, which suggests that moderate-intensity, short-duration exercise in the heat can produce HA in trained subjects. PMID- 2233201 TI - Carbohydrate-electrolyte replacement during a simulated triathlon in the heat. AB - Effects of a 7% carbohydrate-electrolyte drink (CE) or a flavored water placebo (P) on physiological function and performance were compared during a simulated triathlon (ST) in the heat. Ten trained male triathletes performed two STs, consisting of 1.5 km swimming, 40 km cycling, and 10 km running in an environmentally controlled area at self-selected race pace. Subjects consumed 2 ml.kg-1 (130-174 ml) of CE or P following the swim, at 8.0-km intervals during cycling, and at 3.2-km intervals during running. Sweat rate, rectal and mean skin temperatures, perceived exertion, heart rate, plasma osmolality, percent change in plasma volume, total protein, Na+, K+, and lactate were similar during the ST under both drink conditions, but RER and plasma glucose were higher (P less than 0.05) with CE. During the last 4 km of running, VO2 was significantly higher with CE. Mean run time and total ST time were faster with CE (by 1.4 and 1.2 min) although not significantly different (P less than 0.06 and P less than 0.10) from P. Subjects reported no significant difference in nausea, fullness, or stomach upset with CE compared to P. General physiological responses were similar for each drink during 2 h of multi-modal exercise in the heat; however, blood glucose, carbohydrate utilization, and exercise intensity at the end of a ST may be increased with CE fluid replacement. PMID- 2233202 TI - Circulatory and thermal adjustments to prolonged exercise in paraplegic women. AB - The circulatory and thermal responses to 90 min of wheelchair ergometer exercise were examined in five wheelchair dependent (WD) women with low level spinal dysfunction and five able-bodied (AB) women who served as a comparison group. Metabolic rate during exercise was 221 W for WD and 255 W for AB (P greater than 0.05). Oral temperature (Tor), mean skin temperature (Tsk), oxygen uptake (VO2), heart rate (HR), and cardiac output (Qc) were assessed periodically throughout the exercise period. Ambient conditions were 24-25 degrees C and 38-52% relative humidity. A significant group X time interaction was found for Tor (P less than 0.001) and Tsk (P less than 0.001). Tor of the WD group steadily increased during the exercise, whereas the AB group showed a stable Tor. Tsk of WD increased rapidly during the first 5-10 min of exercise and continued to rise at a slower rate throughout the exercise. In contrast, Tsk of AB rose to a peak during the first 10 min and then showed a decreasing trend. VO2 and HR remained stable in both groups throughout the exercise period. Following an initial increase in Qc from minute 10 to minute 20 in both groups, values for WD continually decreased until Qc at 80 min was 14% lower than at 10 min. The findings suggest that the WD women had greater thermoregulatory strain than the AB women as indicated by a higher Tor and Tsk and by an inability to maintain Qc due to paralysis of the lower limbs and perhaps an increase in cutaneous blood volume. PMID- 2233203 TI - Body temperature rhythm and response to pyrogen in exercising and sedentary hamsters. AB - In this study, we tested the hypothesis that daily voluntary exercise results in a chronic elevation in core temperature in the female golden hamster. Temperature and activity were measured by biotelemetry. Hamsters ran 6-7 km per night (12:12 L:D) when permitted access to wheels. No running occurred during the light periods. During the 3rd wk of running, temperatures of exercising hamsters were significantly elevated by 0.5 degree C (P less than 0.001) during the dark period and by 0.3 degree C (P less than 0.003) during the light period compared with sedentary hamsters. Cessation of running removed the difference between groups, and resumption of running restored it. Both the injection of endotoxin and the psychological stress of cage switch resulted in similar peak temperatures in exercising and sedentary hamsters despite higher pre-treatment temperatures in the exercise group. We interpret these results to support the hypothesis that regular exercise may cause an upward resetting of the set-point for body temperature. PMID- 2233204 TI - Daily pattern of %VO2max and heart rates in normal and undernourished school children. AB - The pattern of usage of the VO2max, expressed as %VO2max during ordinary school days, with minute-by-minute heart rate recording, was studied in 106 boys and 83 girls, 6-16 yr of age divided into three age groups (6-8, 10-12, and 14-16 yr), living under economically deprived conditions in Colombia and classified as nutritionally normal or marginally malnourished. In a 12-h period, the 12 groups of children spent, on the average, 7-10 h at less than 30% VO2max, 1.5-4 h at 30 50% VO2max, and an accumulated time of 20-60 min above 50% VO2max. The latter occurred in short bursts rather than during sustained periods. There was a statistically significant but small decrease (approximately -3%) in the average 12 h %VO2max with age but no effects of sex or nutritional status. The overall average was about 25% VO2max in all groups. The data may suggest the existence of the regulation of physical activity to some level easily sustainable for long periods. Expressing the data as 30 min averages during 5 h of school and 5 h of free-time activity allows for the possibility of seeing group differences during shorter periods of time. This may prove useful in exercise training programs and studies of effort in the workplace. PMID- 2233205 TI - Cross-modal exercise prescription at absolute and relative oxygen uptake using perceived exertion. AB - Cross-modal exercise prescription at absolute and relative oxygen uptake using perceived exertion. Med. Sci. Sports Exerc., Vol. 22, No. 5, pp. 653-659, 1990. The validity of cross-modal prescription of exercise intensity based on rated perceived exertion (RPE) was determined for eight men (26 +/- SE 1.9 yr) at absolute and relative VO2. Exercise modes were treadmill (TM), cycle ergometer (C), and bench stepping while pumping 0.91 kg handweights (HB). Relative (Rel) constant load sessions were performed for each mode at 70% of mode-specific VO2 peak. Absolute (Absol) constant load sessions were performed for C and HB at the VO2 equivalent to 70% of TM VO2 peak. The five 12 min sessions were presented on separate days in random order. RPE-Overall during TM-Rel (11.1) was a) lower (P less than 0.05) than C-Absol (12.6) and HB-Absol (12.5) and b) the same as C-Rel (11.3) and HB-Rel (10.7). RPE-Legs during TM-Rel was a) lower (P less than 0.05) than C-Absol and HB-Absol and b) the same as C-Rel and HB-Rel. RPE-Chest a) did not differ between TM-Rel and C-Absol or HB-Absol and b) was lower (P less than 0.05) for C-Rel and HB-Rel than TM-Rel. RPE-Arms was higher (P less than 0.05) for C-Absol, HB-Absol, and HB-Rel than TM-Rel but did not differ between TM-Rel and C-Rel. Oxygen uptake, heart rate, and ventilation during TM-Rel were a) the same as C-Absol and HB-Absol and b) higher (P less than 0.05) than C-Rel and HB Rel. Perceptually based cross-modal prescription of exercise intensity using a psychophysical estimation method is valid provided that the physiological reference is the relative, not the absolute, VO2. PMID- 2233206 TI - Mechanical output about the ankle joint in isokinetic plantar flexion and jumping. AB - The purpose of this study was to compare for a group of ten subjects the mechanical output about the ankle during isokinetic plantar flexion with that during one-legged vertical jumps. For evaluation of the mechanical output the plantar flexion moment of force was related to the angular velocity of plantar flexion. The relationship for isokinetic plantar flexion was obtained using an isokinetic dynamometer; that for plantar flexion in jumping was obtained by combining kinematics and ground reaction forces. It was found that, at any given angular velocity of plantar flexion above 1 rad.s-1, the subjects produced much larger moments during jumping than during isokinetic plantar flexion. In order to explain the observed differences in mechanical output about the ankle, a model was used to simulate isokinetic plantar flexion and plantar flexion during jumping. The model represented both m. soleus and m. gastrocnemius as a complex composed of elastic tissue in series with muscle fibers. The force of the muscle fibers depended on fiber length, shortening velocity (Vfibers), and active state. The input variables of the model were histories of shortening velocities of the complexes, determined from kinematics, and active state. Among the output variables were Vfibers and plantar flexion moment. The simulation results were very similar to the experimental findings. According to the simulation results there are two reasons why at the same angular velocity of plantar flexion larger moments were produced during jumping than during isokinetic plantar flexion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233207 TI - Stance phase knee and ankle kinematics and kinetics during level and downhill running. AB - To study possible mechanisms for muscle soreness in downhill running, ground reaction force and kinematic data were collected on seven male runners during 4.5 m.s-1 level running (LR) and 8.3% downhill grade running (DR). For DR, a force platform was mounted on a sloped concrete block flush with the surface of a ramp. A two-dimensional link segment model was used to calculate net stance phase moments for the knee and ankle. Data were averaged over all subjects for each condition. There was no significant difference (P less than 0.05) between DR and LR for peak flexion velocity, peak extensor moment, or peak power absorption at the knee. Negative work done on the extensor muscles of the knee during stance was significantly greater for DR (58.0 +/- 13 J) than for LR (30.0 +/- 9.0 J). Peak ankle power absorption was significantly greater for DR (619 +/- 85 W) than for LR (396 +/- 180 W). The negative work done on the extensor muscles of the ankle during stance was significantly greater for DR (26.1 +/- 3.2 J) than for LR (12.6 +/- 6.6 J). The results suggest that muscle soreness during DR may be related to high peak power absorption values since the peak joint extensor moments are similar between conditions. PMID- 2233208 TI - The health belief model: predicting compliance and dropout in cardiac rehabilitation. AB - We investigated the health belief model and the health locus of control constructs as predictors of group membership (compliers or dropouts) with cardiac rehabilitation and whether they added predictive utility to routinely assessed patient demographics and health behaviors. Questionnaires were completed on entry into the study by 120 patients with coronary artery disease, and by the end of the 6 month program there were 58 compliers and 62 dropouts. Discriminant function analyses were carried out to determine prediction of group membership. The health belief model predicted group membership 64.6% of the time, explaining 5.2% of the variance. Demographics, health behaviors, and health belief model factors accounted for 21.1% of the variance between compliers and total dropouts with group membership correctly predicted 74.4% of the time; avoidable and unavoidable dropout was correctly predicted 84.2% of the time with 56.9% of the variance explained. Health locus of control did not distinguish between compliers and dropouts. The addition of the health belief model provided additional information about compliance with cardiac rehabilitation beyond that explained by demographic and health behavior variables alone, particularly when predicting avoidable/unavoidable dropout. PMID- 2233209 TI - The accuracy of self-reports of physical activity. AB - This investigation determined the accuracy of self-reports of physical activity compared to observations obtained surreptitiously. Subjects were 44 adults engaged in 1 h of their preferred physical activity while actual activity levels were surreptitiously obtained and compared to immediate self-reported estimates of physical activity. Results indicated that subjects were moderately accurate in recalling their physical activity levels (R = 0.62) but underestimated sedentary activities and overestimated aerobic activities by over 300%. Males overestimated their activity relative to females, and obese subjects underestimated their activity levels compared to normal-weight subjects. Finally, a number of two-way interactions that moderated the accuracy of those subjects engaging in high chronic levels of physical activity were observed. PMID- 2233210 TI - The Caltrac accelerometer as a physical activity monitor for school-age children. AB - The performance of the Caltrac accelerometer was studied in elementary school-age children under field and laboratory conditions. In Study 1, 35 children (20 boys, 15 girls, mean age = 10.8 yr) wore the accelerometer and a heart rate (HR) monitor for 2 d. Caltrac activity counts per hour were compared to the mean "activity HR", which was calculated by subtracting the mean of the five lowest HRs of the day from each recorded HR. Pearson r's between accelerometer and activity HR were 0.54 (P less than 0.001) on day 1 and 0.42 (P less than 0.02) on day 2. Inter-instrument reliability in the field was r = 0.96. Both accelerometer and HR data were significantly correlated with physical activity recalls of the same day. In Study 2, 15 children walked/ran for 10 min at 3, 4, and 5 mph on a horizontal treadmill while wearing two accelerometers. Oxygen uptake was directly measured each minute. Reliability of the Caltracs in the laboratory was 0.89. Activity count correlated r = 0.82 (SEE = 23%) with net calorie cost per kg of body weight. Net caloric expenditure per kg of weight was 0.101 kcal.kg-1.d-1 per Caltrac activity count. These data support the use of the Caltrac accelerometer as a physical activity measure for school-age children, and the objective data tended to corroborate the children's short-term activity recalls. PMID- 2233211 TI - Accurate prediction of VO2max in cycle ergometry. AB - Numerous equations exist for predicting VO2max from the duration (an analog of maximal work rate, Wmax) of a treadmill graded exercise test (GXT). Since a similar equation for cycle ergometry (CE) was not available, we saw the need to develop such an equation, hypothesizing that CE VO2max could be accurately predicted due to its more direct relationship with W. Thus, healthy, sedentary males (N = 115) and females (N = 116), aged 20-70 yr, were given a 15 W.min-1 CE GXT. The following multiple linear regression equations which predict VO2max (ml.min-1) from the independent variables of Wmax (W), body weight (kg), and age (yr) were derived from our subjects: Males: Y = 10.51 (W) + 6.35 (kg) - 10.49 (yr) + 519.3 ml.min-1; R = 0.939, SEE = 212 ml.min-1. Females: Y = 9.39 (W) + 7.7 (kg) - 5.88 (yr) + 136.7 ml.min-1; R = 0.932, SEE = 147 ml.min-1 Using the 95% confidence limits as examples of worst case errors, our equations predict VO2max to within 10% of its true value. Internal (double cross-validation) and external cross-validation analyses yielded r values ranging between 0.920 and 0.950 for the male and female regression equations. These results indicate that use of the equations generated in this study for a 15 W.min-1 CE GXT provides accurate estimates of VO2max. PMID- 2233212 TI - Genucom knee analysis system: reproducibility and database development. AB - The Genucom is a relatively new computerized system that performs a multidimensional analysis of knee laxity. Therefore, the purposes of the present investigation were twofold: 1) to estimate the reproducibility of the testing system in its ability to obtain similar test values on the same test subject within a back-to-back two-test protocol and 2) to develop a database of normal values as a standard against which values of suspected ligament injury can be compared to reliably determine whether, in fact, ligament injury has occurred. In the reproducibility phase of the study, 20 subjects were tested in two trials each of eight tests, yielding 20 separate test values per trial, accounting for each angle of flexion and plane of force tested. Both legs were tested, providing an N of 40. Test-retest correlations of the two trials and dependent t-tests indicated that the Genucom provided generally stable and reproducible results. In the normal value database phase of the study, 218 different subjects were given one trial of the same eight tests. Testing of both legs provided an N greater than 400. Means and standard deviations were calculated for each test. PMID- 2233213 TI - A simulation of speed skating performances based on a power equation. AB - Using kinetics of aerobic and anaerobic power production as measured during supramaximal bicycle tests of five speed skaters of international level, a model of the kinetics of power production during skating is obtained. Velocity time courses of a generalized speed skater were calculated for all Olympic distances (500 m, 1000 m, 1500 m, 5000 m, and 10,000 m) by means of simulation of an equation of produced power, power dissipated to air and ice friction, and rate of change of kinetic energy of the skater. Different strategies of distribution of anaerobic energy during a race were compared. With a single equation it appeared to be possible to simulate the mean split and final times of the five distances realized during the Winter Olympics 1988 within an error which does not exceed 1.6% (mean error in final times: 0.8%). The results show that a fast acceleration (high initial power output) is crucial for the sprinting events (500 m and 1000 m). It is shown that this initial power output level is even more important than the total amount of energy available for a 500 m and 1000 m race. For the long distances the simulations show that skaters should combine a fast but short lasting start with a constant power output following the start in order to minimize air frictional losses. PMID- 2233214 TI - Anthropometric estimation of muscle mass in men. AB - Twelve male cadavers (aged 50-94 yr) were subjected to comprehensive anthropometry, dissection, and weighing of all skeletal muscle. Correlation coefficients of limb girths with total skeletal muscle mass (MM) were high: forearm r = 0.96, mid-thigh r = 0.94, calf r = 0.84, and midarm r = 0.82. These increased when limb girths were corrected (by subtracting pi times the skinfold thickness) to estimate muscle girth. For dimensional consistency, variables in the regression analyses included the product of stature and the square of each corrected girth. For the six unembalmed cadavers, this yielded a three-girth equation for MM (r2 = 0.93; SEE = 1.56 kg), which was then validated using data from the embalmed cadavers. It predicted MM with an SEE of 1.58 kg and r2 = 0.93. Because the values of these SEEs were similar, we pooled the subjects from the two groups to generate the final estimation equation: MM = STAT (0.0553CTG2 + 0.0987FG2 + 0.0331CCG2) - 2445 (SEE = 1.53 kg, r2 = 0.97), where STAT is stature (cm), CTG is thigh circumference corrected for the front thigh skinfold thickness (cm), FG is the uncorrected forearm circumference (cm), and CCG is the calf circumference corrected for the medial calf skinfold thickness (cm). Despite the limitations of the cadaver sample, the proposed equation appears to provide the best estimate of skeletal muscle mass to date, in that it is the only cadaver validated equation and it gives values that are consistent with all known dissection data. PMID- 2233215 TI - In vivo NMR spectroscopy of lithium-7 in humans. AB - The pharmacokinetics of lithium uptake was measured by 7Li NMR spectroscopy at 24.83 MHz in vivo in the brain and muscle of a normal subject and a patient suffering from bipolar affective disorder, using a modified General Electric Signa clinical magnetic resonance imaging system. Comparison was made to standard phantoms to estimate Li concentrations. The levels of Li in brain and muscle were similar, were typically less than the level in serum, and generally tracked the level in serum. The Li level at steady state in the brain of a patient suffering from schizoaffective disorder was measured over a 7-month period. Substantial variation was seen, which showed some correlation with serum level. Serum level peaked about 2 h after a single 300-mg dose at steady state, and muscle level, immediately thereafter. Brain level peaked considerably later at 4 h. Localized in vivo 7Li NMR spectroscopy was demonstrated by acquisition of a 125-cm3 DRESS slice from the occipital region in less than 7 min. PMID- 2233216 TI - Application of interlaced orientation slices in orthogonal planes for system characterization and as a basis for standardized brain sections in multiple oblique positions. AB - Interlaced acquisition of orthogonal spin-echo orientation slices yields saturated intersection lines, which are available for a system characterization (spatial distortions, slice thickness, chemical shift displacement). Additionally, these scout images contain complete information for a transformation of the gradient coordinate system into the oblique coordinate system of the patient, bearing standardized planes for improved image interpretation and quantitative examinations. PMID- 2233217 TI - Aortoiliac and femoropopliteal phase-based NMR angiography: a comparison between FLAG and RSE. AB - To assess the performance of FLAG and RSE NMR angiography 22 aortoiliac (AI) and 22 femoropopliteal (FP) angiograms in 11 healthy males, mean age 38 +/- 7.6 years, were acquired. The image quality was graded in a blinded fashion by two independent readers. The readers grades were not statistically different (kappa = 0.5696). The representation of diagnostic images was 6/11 FLAG and 8/11 RSE AI as well as 8/11 FLAG and 8/11 RSE FP. On back-to-back comparison six RSE AI and seven RSE FP were graded better than their FLAG counterparts. Although these differences did not achieve a statistical significance RSE NMR angiography provided consistently better images and appears preferable for imaging of the peripheral vascular system in normal subjects. PMID- 2233218 TI - NMR imaging in the earth's magnetic field. AB - The most important and very expensive part of a magnetic resonance imaging set-up is the magnet, which is capable of generating a constant and highly homogeneous magnetic field. Here a new MR imaging technique without the magnet is introduced. This technique uses the earth's magnetic field instead of a magnetic field created by a magnet. This new method has not yet reached the stage of medical application, but the first images obtained by MRIE (magnetic resonance imaging in the earth's field) show that the resolution is close to that expected based on sensitivity estimations. PMID- 2233219 TI - An apparatus for applying a mechanical massage to rat hearts inside a wide-bore NMR spectrometer. AB - A device for applying mechanical massage to the isolated perfused rat heart inside a wide-bore NMR spectrometer was developed. This device exerts a squeezing pressure on a fibrillating heart placed inside a NMR spectrometer without interfering with the NMR measurements. It appears that the apparatus is important for obtaining reliable results in the postischemic reperfusion period. PMID- 2233220 TI - Cooperative T1 and T2 effects on contrast using a new driven inversion spin-echo (DISE) MRI pulse sequence. AB - A pulse sequence is presented for obtaining a single image with combined T1/T2 weighting. T2 relaxation is made to increase intensity, in cooperation with the effect of T1 relaxation, by providing T2 weighting with a 90 degrees-180 degrees 90 degrees driven inversion pulse triplet in an inversion recovery method. Unlike the inversion spin-echo method having a short inversion time (TI), signals in the new driven inversion spin-echo (DISE) method need not be negative and the most T1 sensitive region of the recovery curve can be used. Selecting sensitivity to one relaxation time does not degrade the sensitivity to the other relaxation time. T1 sensitivity is thus extended to longer echo times (TE intervals). T2 sensitivity is extended to longer TI intervals, and the combined T1/T2-weighted technique with intermediate TE and TI has highly cooperative and near-maximal T1 and T2 effects on contrast. Intensity is not multiplicatively degraded by T1 and T2 weighting so that the signal-to-noise of the combined T1/T2-weighted method is high. High intensity and T1 and T2 cooperatively occur for a much wider range of relaxation times, and especially for images heavily weighted to the pathologic intermediate and long T1 and T2 regime. PMID- 2233222 TI - Rapid radiofrequency calibration in MRI. AB - A collection of modified procedures for setting rf transmitter levels using a three-pulse sequence is described. Based on a geometrically weighted ratio of four signals, an estimate of the flip angle is calculated and used for an updating prescription. These techniques are designed to perform rapidly yet eschew systematic errors due to relaxation during the pulse sequence. PMID- 2233221 TI - Signal-to-noise in phase angle reconstruction: dynamic range extension using phase reference offsets. AB - The dynamic range of phase-reconstructed magnetic resonance images is compared to that of magnitude-reconstructed images. From analysis of propagation of errors, the phase angle noise is phase-independent and given in radians by sigma ([I])/[I], the noise-to-signal ratio of the corresponding magnitude-reconstructed image. As the phase can range from minus pi to pi, the phase angle dynamic range is 2 pi times that of the signal magnitude. These results agree with experiment, verifying that the noise in the two receiver channels is uncorrelated. An artifact-free technique is presented for correcting phase spillover, which further extends the phase angle dynamic range. The reconstruction-based reference phase is adjusted on a local basis so that the boundary of phase wraparound is reconstructed near the center of the [- pi, pi] interval. For a particular flow study, the phase signal-to-noise was extended over twofold by spillover correction, to a value 15 times that of the magnitude signal-to-noise. PMID- 2233223 TI - The effect of cardiopulmonary bypass on brain and heart metabolism: a 31P NMR study. AB - The development of a large animal preparation using 31P nuclear magnetic resonance (NMR) spectroscopy for the study of cerebral and myocardial metabolism during cardiopulmonary bypass (CPB) is reported. The effect of normothermic CPB on myocardial and cerebral metabolism was evaluated. Adolescent sheep were used which have low levels of 2,3-diphosphoglycerate, a compound which can interfere with the calculation of intracellular pH and inorganic phosphate content. CPB was performed using standard procedures modified for the presence of a high magnetic field and limited access to the animal. High quality 31P NMR data were obtained from the brains and hearts of these animals before and during normothermic CPB. These results demonstrate that the initiation of normothermic CPB does not change high energy phosphate levels or intracellular pH. In particular, the decreased myocardial oxygen demand associated with CPB is not associated with improvement in the levels of adenosine triphosphate or phosphocreatine. The measurements of energy metabolism and intracellular pH of the brain and heart during CPB were possible within the constraints of the NMR experiment without compromising the CPB procedure. Combining NMR and CPB techniques permits future studies of cerebral and myocardial metabolism, especially those relating to ischemia. PMID- 2233224 TI - Application of reverse-DEPT polarization transfer pulse sequence to study the metabolism of carbon-13-labeled substrates in perfused organs by 1H NMR spectroscopy. AB - Metabolism of 13C-enriched metabolites can be advantageously studied by reverse polarization transfer methods. In this work an improved reverse-DEPT sequence has been applied for the first time on perfused organs in a 20-mm probe. The metabolic fate of 99% enriched [2-13C]acetate perfused in excised rat liver and heart has been documented. PMID- 2233225 TI - In vitro 31P NMR spectroscopy of the reproductive organs of the male rat: an improved preparation method. AB - In vitro 31P spectroscopy can be applied to disentangle the broad resonances in in vivo 31P NMR spectra of the reproductive organs of the male rat. However, adenosinetriphosphate (ATP) and glycerophosphocholine (GPC), present in large amounts in vivo, are nearly completely absent in vitro. With a modified PCA extraction method, in which the organs were lyophilized before extraction, a large amount of ATP and GPC could be found in vitro. This new extraction method is probably not only restricted to in vitro analysis of the testis but is likely to be useful for analysis of other organs such as kidney and liver. PMID- 2233226 TI - High-speed line scan MR angiography. AB - We describe a system which forms MR angiographic images at high speed. Multiple axial sections are imaged sequentially using a 2DFT GRASS sequence with TR/TE 50/15 ms, 64 phase encodings per image. Reconstruction and projection of each image are performed immediately (within 220 ms) after data for that image are acquired. The projection angiogram is constructed line by line as the scan progresses, thereby totally eliminating any additional time required for reconstruction and projection. PMID- 2233227 TI - A simple method of generating variable T1 contrast images using temporally reordered phase encoding. AB - A rapid method of generating T1 images by means of an inversion pulse followed by a fast low-angle imaging experiment is presented. The T1 contrast is manipulated by a temporal reordering of the phase-encoding gradient, resulting in an almost completely free choice of T1 contrast, without any extra restriction on the size of the data acquisition matrix. The intrinsic rapidity of the sequence renders it insensitive to motion artifacts and lends itself to multipoint T1 calculations. The method is particularly well suited to high-field imaging. PMID- 2233229 TI - Multislice snapshot FLASH using SIMUSIM. AB - A combination of the SIMUSIM technique and snapshot FLASH which allows efficient multislice snapshot FLASH imaging is described. Simultaneously acquired images of deliberate slice position and thickness are obtained with an increased SNR compared to standard time sequential multislice experiments. Experimental results show four coronal cross sections through the human head measured in four acquisitions. PMID- 2233228 TI - 1H MR imaging of anatomical compartments within the finger flexor muscles of the human forearm. AB - Fast T2-weighted 1H MRI following exercise allows investigation of the location of muscle fiber activity within skeletal muscle. Using this method, we have demonstrated that the finger flexor muscles of the human forearm consist of anatomical compartments, located at various depths, which are involved individually in flexion of the index, middle, or ring and little fingers. The results of this study indicate that the exercise protocol in 31P MRS studies of the finger flexor muscles of the human forearm, in which a small surface coil is used for detection, should be carefully reviewed. PMID- 2233230 TI - A chronic granulomatous syndrome of unknown origin. AB - A small clinically distinct group of patients with widespread tissue granulomata are described. The principal presenting symptoms are malaise, fever, and weight loss, although a wide variety of complaints are documented. Pulmonary involvement is uncommon. The granulomata are noncaseating with a few multinucleate giant cells and some surrounding chronic inflammatory infiltrate. There is no evidence of an associated arteritis. The disease has a relapsing and remitting course and although it may require treatment with immunosuppressive drugs, particularly if the kidneys are involved, the prognosis is relatively good. We propose that this entity be called granulomatous syndrome of unknown origin. The characteristics that set this syndrome apart from the other granulomatous vasculitides are discussed. The current limited understanding of granuloma formation does not allow us to propose a definite etiology for this condition. It is emphasized that it is not helpful to encompass it within a label of sarcoidosis. First, it may only serve to confuse the doctor in assessing and treating this very particular group of patients. Secondly, it may hinder future attempts to understand the different pathogenetic mechanisms underlying the various conditions in which granulomata may arise. PMID- 2233231 TI - Pancreaticopleural fistula. Report of 7 patients and review of the literature. AB - Pancreaticopleural fistula is an uncommon clinical condition. Its presentation is often confusing because of the paucity of clues suggestive of pancreatic disease and the preponderance of pulmonary symptoms and signs. Most patients are alcoholics but only one-half will have a clinical history of previous pancreatitis. Pleural effusions are large, recurrent, and highly exudative in nature. Many patients go through extensive pulmonary evaluation before the pancreas is identified as the site of primary pathology. An elevated serum amylase may be the first clue to the diagnosis. However, the key to the diagnosis is a dramatically elevated pleural fluid amylase. Effusions in association with acute pancreatitis, esophageal perforation, and thoracic malignancy are important to consider in the differential diagnosis of an elevated pleural fluid amylase but are usually easy to exclude. Computed tomography is excellent in defining pancreatic abnormalities and should be the first abdominal imaging study in suspected cases. Endoscopic retrograde cholangiopancreatography (ERCP) is used as a diagnostic tool only in confusing cases. Although no systematic study evaluates medical versus surgical therapy, we recommend an initial 2 to 4-week trial of medical therapy, including allowance of no oral intake, total parenteral nutrition, chest tube thoracostomy, and possibly a regimen of somatostatin or its analogs. The major complication in these patients is superinfection, which results in significant morbidity and mortality. Failure of medical therapy should be considered failure of pleural effusion(s) to clear, recurrence after reinstatement of oral intake, or superinfection. For those patients who fail to benefit from medical therapy, surgery is indicated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233232 TI - Primary central nervous system lymphoma in patients with and without the acquired immune deficiency syndrome. A retrospective analysis and review of the literature. AB - Twenty-two cases of PCL were reviewed, in which 9 patients had AIDS and 13 did not. A review of the literature identified 247 cases of AIDS-related PCL. Differences between patients with AIDS and immunocompetent PCL were noted in our series. AIDS-related PCL when compared to non-AIDS PCL in our series has the following notable clinical features: 1) significantly younger age at presentation, median age 34 versus 59 years; 2) significantly higher incidence of B symptoms, 44% versus 8%; 3) worse median performance status at presentation, 3 versus 1; and, 4) shorter median survival, 3 versus 10 months. Differences in performance status and survival, however, were not significant. AIDS-related PCL is further characterized by frequent (44%) ring-enhancing mass lesions on head CT scan, a finding that makes it clinically difficult to distinguish from toxoplasmosis. Median survival appears to be improved in the absence of opportunistic infection at time of diagnosis of PCL, 6 versus 2 months. The therapeutic approach to patients with PCL, with and without AIDS, is variable. Combined modality therapy may improve the survival in patients with non-AIDS PCL. Therapy for patients with AIDS-related PCL is tailored to the status of the individual and it is, therefore, difficult to make comparisons to non-AIDS PCL patients. AIDS patients are often too ill to tolerate aggressive surgery or systemic treatment and in this instance, radiotherapy alone may be an acceptable alternative. Nonetheless, overall survival for patients with AIDS-related and non AIDS PCL remains poor. PMID- 2233235 TI - [Occupational medicine in the XXI century--the role and tasks of the Institute of Occupational Medicine in Lodz]. AB - The article presents strategy and goals of study program in occupational health for the years 1991-1995. Five strategy lines and corresponding to them goals have been determined. These are: (1) Development and implementation of detailed programmes for preventing the main occupational and work-related diseases causing the substantial social-economic losses to limit health effects induced by occupational exposure; (2) Development, integration and improvement of chemical safety system to limit environmental exposure to chemicals and to reduce health consequences due to living and working environment pollution with chemicals; (3) Development and implementation of methods of psychophysical effort load evaluation, methods of proper vocational selection and principles of preventive action to limit work strenuosness and changes in health status induced by process and organization of work; (4) Increasing the effectiveness and extension of health care and preventive activities for national economy workers; (5) Development and practical implementation of modern programmes of training in occupational health (under- and postgraduate) together with preparing didactic aids and scientific-technical information. The last line of study programme will be preceded by discussion taking into account the currently available financial means and scientific facilities. PMID- 2233233 TI - Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature. AB - Histoplasmosis is a serious opportunistic infection in patients with AIDS, often representing the first manifestation of the syndrome. Most infections occurring within the endemic region are caused by exogenous exposure, while those occurring in nonendemic areas may represent endogenous reactivation of latent foci of infection or exogenous exposure to microfoci located within those nonendemic regions. However, prospective investigations are needed to prove the mode of acquisition. The infection usually begins in the lungs even though the chest roentgenogram may be normal. Clinical findings are nonspecific; most patients present with symptoms of fever and weight loss of at least 1 month's duration. When untreated, many cases eventually develop severe clinical manifestations resembling septicemia. Chest roentgenograms, when abnormal, show interstitial or reticulonodular infiltrates. Many cases have been initially misdiagnosed as disseminated mycobacterial infection or Pneumocystis carinii pneumonia. Patients are often concurrently infected with other opportunistic pathogens, supporting the need for a careful search for co-infections. Useful diagnostic tests include serologic tests for anti-H. capsulatum antibodies and HPA, silver stains of tissue sections or body fluids, and cultures using fungal media from blood, bone marrow, bronchoalveolar lavage fluid, and other tissues or body fluids suspected to be infected on clinical grounds. Treatment with amphotericin B is highly effective, reversing the clinical manifestations of infection in at least 80% of cases. However, nearly all patients relapse within 1 year after completing courses of amphotericin B of 35 mg/kg or more, supporting the use of maintenance treatment to prevent recurrence. Relapse rates are lower (9 to 19%) in patients receiving maintenance therapy with amphotericin B given at doses of about 50 mg weekly or biweekly than with ketoconazole (50-60%), but controlled trials comparing different maintenance regimens have not been conducted. Until results of such trials become available, our current approach is to administer an induction phase of 15 mg/kg of amphotericin B given over 4 to 6 weeks, followed by maintenance therapy with 50 to 100 mg of amphotericin B given once or twice weekly, or biweekly. If results of a prospective National Institutes of Allergy and Infectious Disease study of itraconazole maintenance therapy document its effectiveness, alternatives to amphotericin B may be reasonable. PMID- 2233234 TI - Extrapulmonary pneumocystosis: clinical features in human immunodeficiency virus infection. AB - Pneumocystis carinii infection is reported with increasing frequency as a cause of disease outside of the respiratory tract in patients with human immunodeficiency virus (HIV) infection. Extrapulmonary pneumocystosis is not limited to patients in any discrete risk group for HIV infection. Patients with HIV infection who develop extrapulmonary pneumocystosis frequently do not have concurrent P. carinii pneumonia. Signs and symptoms of extrapulmonary pneumocystosis are nonspecific but when present are frequently referable to the tissues or organs involved. Extrapulmonary pneumocystosis can be diagnosed by examination of tissue biopsies from affected sites using standard histologic techniques. Therapy with antimicrobial agents used to treat P. carinii pneumonia has been effective in some patients. An association between use of aerosolized pentamidine for prevention of P. carinii pneumonia and development of extrapulmonary pneumocystosis has been suggested but remains unconfirmed. Other factors such as the use of zidovudine and duration of immunodeficiency may also be important to the pathogenesis of extrapulmonary pneumocystosis. Further studies are needed to better identify risk factors that may predispose patients to the development of extrapulmonary pneumocystosis. PMID- 2233236 TI - [Diseases of the upper respiratory tract in furniture industry workers]. AB - A group consisting of 100 cabinet-makers (at average age of 44.6 +/- 12.8 years) employed at furniture manufacturing plants exposed to wood dust at concentrations exceeding several times (from 7 to 8 times) the hygienic standard was subject to examination. The higher, as compared to the data for general population, prevalence of chronic rhinitis , pharyngitis, laryngitis--among other--atrophic rhinitis and pharyngitis which occurred in 37% of examined population, increasing together with prolonging period of exposure was found. At the same time there have not been found any cases of allergy, nasal or nasal sinuses neoplasms which could be a result of exposure to wood dust. PMID- 2233237 TI - [Olfactory adaptation as a factor limiting the warning role of odors]. AB - Threshold concentrations of olfactory sensation of odorants change due to adaptation to polluted atmosphere. The study was aimed at determination of trimethylamine and n-butanol threshold concentrations of olfactory sensation under standard laboratory conditions. The results were analysed from two viewpoints: the role of odour as a warning against chemical hazard, a possibility of using the shift of sensation threshold of appropriately selected reference standards as a measure of discomfort created by odours in working environment. PMID- 2233238 TI - [Evaluation of the status of nasal mucosa in workers engaged in the production of chlorfenvinphos (enolophos)]. AB - In 41 men aged from 23 to 59 years (on an average--37.5 years) and employment duration from 1-10 years (on an average--4.9 years) working in the division of chlorfenvinphos synthesis and manufacturing "enolophos"--a preparation for agriculture, laryngological examinations were carried out including cytologic assessment of nasal mucosa and olfactometric tests. Rhinoscopy as well as cytological examinations confirmed the higher prevalence of nasal mucosa changes of inflammatory or allergic character as compared to the control group. The association between duration of employment and the changes perceived was found. Simultaneously olfactometric tests revealed in this group of workers frequent lowering of odours sensation and identification threshold. PMID- 2233239 TI - [Effect of occupational exposure to lead, zinc and cadmium on various indicators of the circulatory system of metallurgical workers]. AB - 386 workers occupationally exposed to Pb, Cd and Zn in metallurgical plants were examined to evaluate the influence of lead, cadmium and zinc on circulatory system. The workers were divided into groups according to age and degree of poisoning with metals. Control group included 325 persons, selected according to age, occupationally unexposed to metals. All groups of persons were subject to medical examinations including ECG. Significantly higher prevalence of systolic murmur and heart ventricles repolarization disorders was found in the group exposed irrespective of the age of particular individuals. The workers exposed aged up to 40 years develop more frequently arterial hypertension and heart rhythm disorders. The results obtained indicate that Pb, Cd and Zn adversely affect the circulatory system. PMID- 2233240 TI - [Acid phosphatase and non-specific esterase activities in peripheral blood lymphocytes of coke plant workers]. AB - In 32 workers of coking plants cytoenzymatic reaction was examined in lymphocytes peripheral blood to determine the presence of acid phosphatase and unspecific esterase expressed in total score values. Statistically significant decrease of unspecific esterase activity and lower mean values of acid phosphatase activity were found as compared to the results obtained in the control group. It seems that periodical determinations of cytoenzymatic activity of unspecific esterase in lymphocytes of peripheral blood may be useful in assessment of biological effects of occupational exposure in coking plants workers. PMID- 2233241 TI - [Study of morbidity among industrial workers based on periodic medical examinations]. AB - The report presents the results of periodical medical examinations in a group of 530 men working in machine-building industrial plant. Average age of men examined was 37.4 +/- 11.4 years. The population examined was exposed to silica dust, noise, vibration, carbon monoxide, benzene irritative gases. Most of them worked in a forced position: standing and stooping. In the population examined 1632 cases of chronic diseases were found and the calculated morbidity rate amounted to 308.0 per 100 workers. Calculating the morbidity rate some not well determined states and symptoms as well as oral cavity, salivary glands and maxillary diseases were excluded. It was found that in the population examined 91.1% of workers developed chronic diseases and only 8.9% could be conventionally considered as healthy subjects. The report presents structure of diseases and their prevalence. A conclusion is drawn that in workers of machine-building industry exposed to many occupational hazards the prevalence of some chronic diseases is higher than in some other industrial branches. It is recommended to adopt age criteria, apart from occupational exposure, as one of principal measures of effectiveness of health care provided by occupational health care units. PMID- 2233242 TI - [Effect of the selection of reference population on the evaluation of the degree of the risk of death among industrial cohorts]. AB - The report is devoted to one of the main problems of studies on death rate in industrial cohorts. In the study on cohort consisting of workers of asbestos processing plant in Lodz, the general population of Poland was selected as a reference population. Such method of analysis was used chiefly due to the fact that the data for local population of the Lodz district were unavailable. The report presents a comparative analysis of mortality based on the standardized death rate calculated for the total Polish and the Lodz district populations for the period for which appropriate data were available (1974-1985). The conclusions resulting from both analyses point to overmortality due to some selected causes regardless which reference population was taken into consideration although absolute number of these surpluses depends on selection of reference population. PMID- 2233243 TI - [Biochemical basis of the effect of organophosphate pesticides on humans]. AB - The rapidly increasing use of organophosphorous compounds in everyday life causes that greater attention should be paid to the toxic effect exerted by these compounds on human organism. Acute toxic effects have been relatively well known whereas chronic effects require further studies. It is essential especially in view of progressive pollution of environment. The report presents data on the mechanism of action of organophosphorous compounds on human organism with particular regard to those effects which lead to the so called delayed neuropathy. The occurrence of that phenomenon as a result of single exposure to high concentrations of organophosphorous compounds as well as due to long-term exposure to the relatively low doses of those substances has been discussed. PMID- 2233244 TI - Molecular pathology of type 1 diabetes. AB - Evidence from epidemiological and histopathologic studies in humans with autoimmune type 1 (insulin-dependent) diabetes suggests that beta-cell destruction within the islets of Langerhans progresses through a number of stages. In this review we draw on recent experimental evidence in an attempt to define the molecular pathology of these stages. Stage 1 is postulated to be initiated by modification of the beta cell by virus, chemical or other factors, leading to the production of interferon-alpha, hyperexpression of major histocompatibility complex (MHC) class I molecules and induction of MHC class II molecules. Experiments in transgenic mice suggest that overexpression of MHC molecules is in itself detrimental to beta-cell function. Shedding of antigen(s) from dying beta cells in combination with hyperexpression of MHC molecules may be a powerful immunogenic stimulus. Stage 2 commences with infiltration of the islets by immuno-inflammatory cells (termed insulitis). It is proposed that production of cytokines from the infiltrating cells induces "phenotypic switching" in beta cells, with further upregulation of MHC molecules and the induction of intracellular adhesion molecule-1 expression and interleukin-6 production. Together, these properties are seen as a prerequisite for the presentation of autoantigen by beta cells to adherent T lymphocytes and autoimmune activation. The final stage encompasses autoimmune-mediated destruction of the beta cells by the targeted delivery of cytotoxic cytokines and other mediators. PMID- 2233245 TI - Development of antigen-specific therapies for autoimmune disease. AB - Reversal of autoimmune disease with monoclonal antibodies to polymorphic determinants associated with class II gene products of the major histocompatibility complex (MHC) and to T-cell receptor variable region segments has been demonstrated in animal models. Recent studies have shown that it is also possible to use mutant peptides to block recognition of self-antigen associated with MHC by T-cells that mediate autoimmune disease. These mutant peptides have been used to prevent the model autoimmune condition experimental allergic encephalomyelitis. The possibility of extending these approaches to human disease is discussed. PMID- 2233246 TI - Tolerance to self-antigens in transgenic mice. AB - Transgenic mice represent a versatile experimental approach for understanding the pathways by which the immune system regulates responsiveness to self-antigens, thereby establishing self-tolerance. The introduction of immunoglobulin and T cell receptor genes with specificity for self-antigens into the germline of mice has enabled the fate of self-reactive lymphocyte precursors to be followed in vivo. The influence of both developmentally regulated, and tissue-specific gene expression on tolerance to self-antigens has been addressed using transgenic mice expressing novel self-antigens under the transcriptional control of heterologous gene promoters. The generation of transgenic mice expressing structurally altered forms of self-antigens has allowed the role of antigen-processing in the induction of tolerance to be examined. Significantly, while these studies have confirmed the classically derived principles of immunological self-tolerance, they also point to the existence of pathways, as yet undefined, by which tolerance to self-antigens may be implemented and maintained. PMID- 2233247 TI - Sequence of a cDNA encoding human galactose-1-phosphate uridyl transferase. AB - We report a revised sequence of a cDNA that encodes a human galactose-1-phosphate uridyl transferase. The cDNA is 1295 bases in length and encodes a 43,000 Mr protein. The sequence was derived from a cDNA clone isolated from a transformed human lymphoblast cell line and amplified in a polymerase chain reaction. The revised sequence reveals a higher degree of amino acid conservation between the human enzyme and the homologous enzymes from Escherichia coli and yeast than was previously thought to exist. PMID- 2233248 TI - Surface-induced swarmer cell differentiation of Vibrio parahaemolyticus. AB - Vibrio parahaemolyticus distinguishes between life in a liquid environment and life on a surface. Growth on a surface induces differentiation from a swimmer cell to a swarmer cell type. Each cell type is adapted for locomotion under different circumstances. Swimmer cells synthesize a single polar flagellum (Fla) for movement in a liquid medium, and swarmer cells produce an additional distinct flagellar system, the lateral flagella (Laf), for movement across a solid substratum, called swarming. Recognition of surfaces is necessary for swarmer cell differentiation and involves detection of physical signals peculiar to that circumstance and subsequent transduction of information to affect expression of swarmer cell genes (laf). The polar flagellum functions as a tactile sensor controlling swarmer cell differentiation by sensing forces that restrict its movement. Surface recognition also involves a second signal, i.e. nutritional limitation for iron. Studying surface-induced differentiation could reveal a novel mechanism of gene control and lead to an understanding of the processes of surface colonization by pathogens and other bacteria. PMID- 2233249 TI - The normally periplasmic enzyme beta-lactamase is specifically and efficiently translocated through the Escherichia coli outer membrane when it is fused to the cell-surface enzyme pullulanase. AB - Hybrid proteins were constructed in which C-terminal regions of the bacterial cell surface and extracellular protein pullulanase were replaced by the mature forms of the normally periplasmic Escherichia coli proteins beta-lactamase or alkaline phosphatase. In E. coli strains expressing all pullulanase secretion genes, pullulanase-beta-lactamase hybrid protein molecules containing an N terminal 834-amino-acid pullulanase segment were efficiently and completely transported to the cell surface. This hybrid protein remained temporarily anchored to the cell surface, presumably via fatty acids attached to the N terminal cysteine of the pullulanase segment, and was subsequently specifically released into the medium in a manner indistinguishable from that of pullulanase itself. These results suggest that the C-terminal extremity of pullulanase lacks signal(s) required for export to the cell surface. When beta-lactamase was replaced by alkaline phosphatase, the resulting hybrid also became exposed at the cell surface, but exposition was less efficient and specific release into the medium was not observed. We conclude that proteins that do not normally cross the outer membrane can be induced to do so when fused to a permissive site near the C terminus of pullulanase. PMID- 2233250 TI - Sequence, localization and function of the invasin protein of Yersinia enterocolitica. AB - The inv locus of Yersinia enterocolitica is sufficient to convert a non-invasive Escherichia coli K12 strain into a microorganism that is able to penetrate cultured mammalian cells. The nucleotide sequence of inv reveals an open reading frame corresponding to an 835-amino-acid protein that is homologous to the invasin protein from Yersinia pseudotuberculosis. A polyclonal antiserum elicited by a synthetic peptide corresponding to the C-terminal 88 amino acids of this open reading frame detected a unique 100 kD protein in cell lysates of Y. enterocolitica strain 8081 c and in an E. coli strain harbouring the cloned inv gene. This protein localized to the outer membranes of both microorganisms and was cleaved by low concentrations of extracellular trypsin. HEp-2 cells were shown to attach to surfaces coated with bacterial outer membranes containing invasin and this attachment was destroyed by treatment of the membranes with trypsin. Thus it appears that the invasin protein from Y. enterocolitica is able to mediate both attachment to and entry of cultured epithelial cells. PMID- 2233251 TI - Streptococcus pneumoniae possesses canonical Escherichia coli (sigma 70) promoters. AB - Seventeen DNA fragments from Streptococcus pneumoniae were randomly cloned in Escherichia coli with selection for promoter activity. The fragments were sequenced and the promoter locations were determined by primer extension analysis. Examination for sites similar to the E. coli major consensus promoter sequence revealed such a site in each of the seventeen fragments, located five to eight base pairs upstream of the point at which transcription was initiated in the E. coli host. Thus, the abundance of promoter activity found in pneumococcal DNA cloned in E. coli hosts arises primarily from sigma-70-type promoter structures. Combined with the observation that such sequences are usually found just upstream of, but not within, pneumococcal genes, this implies that one class (perhaps the major class) of pneumococcal promoters closely resembles the canonical E. coli promoter consensus. PMID- 2233252 TI - Characterization of the virB operon of an Agrobacterium tumefaciens Ti plasmid: nucleotide sequence and protein analysis. AB - The virulence regulon of the Agrobacterium tumefaciens TiC58 plasmid is composed of six operons, virA, virB, virG, virC, virD and virE, which direct the transfer of T-DNA into plant cells. The 9.5 kbp virB operon is the largest of these operons and its entire nucleotide sequence was determined and found to contain eleven open reading frames (ORFs). Gene fusions of each VirB ORF to T7 phi 10 were made and overexpressed in Escherichia coli to confirm that they encode proteins of predicted size. Hydrophobic analysis of these peptide sequences revealed nine proteins that contain hydrophobic spanning regions including signal peptide-like sequences. These data suggest that the majority of VirB proteins may associate with bacterial cell membranes, while the two additional proteins possess a potential ATP-binding site. Strong homologies in amino acid sequences were observed between nopaline- and octopine-type plasmids. Specific differences in amino acid sequence encoded by VirB ORFs of nopaline and octopine Ti plasmid and a functional role of the gene products are discussed. PMID- 2233253 TI - Isolation and characterization of the recA gene of Bordetella pertussis. AB - This report describes the detection and cloning of the Bordetella pertussis recA gene. Escherichia coli clones having recombinant plasmids containing the B. pertussis recA gene were isolated by complementing an E. coli RecA- mutant's inability to survive in the presence of methylmethanesulphonate (MMS). This gene was shown to complement the deficiency of E. coli RecA- strains to tolerate the DNA-damaging effects of both a chemical agent and ultraviolet light (u.v.). Deletion mapping experiments localized the gene to a 2.5 kb StuI-EcoRI fragment, and expression of the gene in E. coli resulted in the production of a 40 kD protein. These data strongly suggest that a region of the B. pertussis chromosome that encodes RecA-like activity has been isolated and cloned. PMID- 2233254 TI - Identification and characterization of a porcine-specific transferrin receptor in Actinobacillus pleuropneumoniae. AB - All six strains of Actinobacillus pleuropneumoniae screened for the ability to use different transferrins as a source of iron for growth were capable of using porcine but not human, bovine, or avian transferrins. A specific binding activity for porcine transferrin (pTf) was expressed in cells grown in the presence of specific iron-chelators and was repressed by addition of excess iron. Two iron repressible outer-membrane proteins of 105 and 56 kD were specifically isolated from serotype 1, 2 and 7 strains of A. pleuropneumoniae by an affinity-isolation method using biotinylated porcine transferrin and streptavidin-agarose. PMID- 2233256 TI - COBIOTECH's role in biotechnology worldwide. AB - Curious or sceptical friends often ask, 'What and why is COBIOTECH? What is it doing?'. After serving as President during its formative first years, I attempt here to provide information for the curious and allay concerns of the sceptics about COBIOTECH's emerging role in biotechnology internationally. PMID- 2233255 TI - Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super-gene family. AB - A Staphylococcus epidermidis plasmid conferring inducible resistance to 14 membered ring macrolides and type B streptogramins has been analysed and the DNA sequence of the gene responsible for resistance determined. A single open reading frame of 1.464 kbp, preceded by a complex control region containing a promoter and two ribosomal binding sites, was identified. The deduced sequence of the 488 amino-acid protein (MsrA) revealed the presence of two ATP-binding motifs homologous to those of a family of transport-related proteins from Gram-negative bacteria and eukaryotic cells, including the P-glycoprotein responsible for multidrug resistance. In MsrA, but not these other proteins, the two potential ATP-binding domains are separated by a Q-linker of exceptional length. Q-linkers comprise a class of flexible interdomain fusion junctions that are typically rich in glutamine and other hydrophilic amino acids and have a characteristic spacing of hydrophobic amino acids, as found in the MsrA sequence. Unlike the other transport-related proteins, which act in concert with one or more hydrophobic membrane proteins, MsrA appears to function independently when cloned in a heterologous host (Staphylococcus aureus RN4220). MsrA might, therefore, interact with and confer antibiotic specificity upon other transmembrane efflux complexes of staphylococcal cells. The active efflux of [14C]-erythromycin from cells of S. aureus RN4220 containing msrA has been demonstrated. PMID- 2233257 TI - Processing speed and mental retardation: deadline procedures indicate fixed and adjustable limitations. AB - Brewer and Smith (1984) showed that control mechanisms mediating speed-accuracy regulation contribute to retarded-nonretarded differences in processing speed, with poorly controlled trial-to-trial RT adjustments underlying the greater RT variability of retarded individuals. In Experiment 1, response deadlines controlled processing time, thus minimizing the influence of such control mechanisms. The obtained speed-accuracy relations showed that retarded subjects were unable to match nonretarded subjects' accuracy when responding as rapidly, thus indicating structural limitations on processing speed. The results of Experiment 2 showed, however, that significant adjustments to retarded subjects' processing speed--exceeding those produced by practice--are achievable. Extended training at a short deadline led to tighter control of RT adjustments, with substantial improvements in mean RT when subjects transferred to a self-paced RT task. PMID- 2233258 TI - Role of the preprobe delay in memory-scanning tasks. AB - In a variation of Sternberg's (1966, 1969) memory-scanning task not requiring an explicit negative response, Diener (1988) found that a preprobe delay was necessary to produce the usual set-size effect. In Experiment 1 of the present study, the effect of the preprobe delay was investigated in the typical two response task. In the absence of a preprobe delay, the function relating response latency to set size was virtually flat for negative responses, but was described by a slope of about 18 msec/item for positive responses. Further research suggested that the reduced set-size effect in the absence of a preprobe delay is the result of expectancy effects usually controlled by the preprobe delay. Informing the subject of the size of the memory set before it was presented (Experiment 2) produced a set-size effect of the usual magnitude in the absence of a preprobe delay. Experiment 3 was designed to assess the effects of expectancy in the absence of a memory search. A task similar in stimulus arrangement to the memory-scanning task but requiring the subject to indicate whether the last digit in the set was odd or even produced a decrease in response latency with set size of 29 msec/item in the absence of a preprobe delay. PMID- 2233259 TI - Cuing efficiency in a Stroop-like task with visual half-field presentation. AB - Stroop-like stimuli were presented to either the left or the right visual half field. Subjects responded to the identity of the words above and below (the target dimension), which appeared above or below a reference point (the cuing dimension). Automatic Stroop-like effects were assessed as the difference in reaction times between congruent trials (e.g., above the reference point) and incongruent trials (e.g., above below the reference point) when both trial types were equally frequent. In blocks in which most trials were of one type (e.g., 80% congruent trials), controlled Stroop-like effects could be assessed. Automatic Stroop-like effects remained unchanged under different task manipulations. In contrast, controlled Stroop-like effects were reduced by lowering cue-response compatibility and by increasing the response alternatives from two to four. Thus, similar to other cuing effects, controlled Stroop-like effects are susceptible to manipulations that affect the response-decision stage and appear to involve response-selection processes. The resources supporting these response-selection decisions were not hemisphere-specific, and were sufficiently nonspecific that interference from a memory-load task was found. When resources were scarce, a consistent bias to attend to stimuli presented or responded to on the right was evident. PMID- 2233260 TI - Physical interaction and association by contiguity in memory for the words and melodies of songs. AB - Three experiments were designed to investigate two explanations for the integration effect in memory for songs (Serafine, Crowder, & Repp, 1984; Serafine, Davidson, Crowder, & Repp, 1986). The integration effect is the finding that recognition of the melody (or text) of a song is better in the presence of the text (or melody) with which it had been heard originally than in the presence of a different text (or melody). One explanation for this finding is the physical interaction hypothesis, which holds that one component of a song exerts subtle but memorable physical changes on the other component, making the latter different from what it would be with a different companion. In Experiments 1 and 2, we investigated the influence that words could exert on the subtle musical character of a melody. A second explanation for the integration effect is the association-by-contiguity hypothesis, which holds that any two events experienced in close temporal proximity may become connected in memory such that each acts as a recall cue for the other. In Experiment 3, we investigated the degree to which simultaneous presentations of spoken text with a hummed melody would induce an association between the two components. The results gave encouragement for both explanations and are discussed in terms of the distinction between encoding specificity and independent associative bonding. PMID- 2233262 TI - Vivid memories of emotional events: the accuracy of remembered minutiae. AB - It has been claimed that emotional arousal causes a narrowing of attention, and, therefore, impoverished memory encoding. On this view, if details of an emotional event are reported subsequently, these details must be after-the-fact reconstructions that are open to error. Our study challenges these claims. Using a long-term (2-week), incidental learning procedure, we found that emotion promotes memory both for information central to an event and for peripheral detail. This contrasts with the results of explicit instructions to remember or to attend closely to the event, both of which seem to promote memory for the event's gist at the expense of detail. The likely mechanisms underlying these effects are discussed. PMID- 2233263 TI - On the differential nature of implicit and explicit memory. AB - In this article, we report two experiments that provide further evidence concerning the differential nature of implicit and explicit memory. In Experiment 1, subjects first undertook a sentence-verification task. While carrying out this task, half of the subjects were also required to carry out a secondary processing task involving tone monitoring. Twenty-four hours later, the subjects' memory for target items in the sentence-verification task was tested explicitly by means of a recognition task and implicitly by examining the extent to which the items primed fragment completion. Recognition performance was significantly impaired by the imposition of secondary processing demands during the original learning phase. In contrast, fragment completion was completely unaffected by this additional processing, even though substantial priming was observed. In Experiment 2, we examined whether priming in fragment completion is influenced by the nature of repetition during initial learning. Subjects studied a list of target items that were each repeated twice. Half the items were repeated immediately (lag 0) and half were repeated after six intervening items (lag 6). Memory for the items was assessed by recognition and by priming in fragment completion. Recognition was affected by lag, with lag 6 items being recognized better than lag 0 items. However, although significant priming was obtained, the extent of this priming was uninfluenced by lag. These data indicate two additional dimensions along which implicit and explicit memory differ and, furthermore, they support recent conceptualizations of processing differences underlying these two forms of memory. PMID- 2233261 TI - Processes underlying dimensional interactions: correspondences between linguistic and nonlinguistic dimensions. AB - In six experiments, we examined speeded classification when one dimension was linguistic and the other was nonlinguistic. In five of these, attributes on the dimensions corresponded meaningfully, having in common the concepts "high" and "low." For example, in Experiment 1, the visually presented words HI and LO were paired with high- or low-pitched tones; in Experiment 2, the dimensions were visual words and vertical position, in Experiment 3, they were spoken words and position, and in Experiments 4 and 5, spoken words and pitch. For each dimension in each pair, subjects suffered Garner interference when dimensions were varied orthogonally. Garner interference remained constant across 15 blocks of trials (Experiment 5). Subjects also showed significant congruity effects in all experiments, with attributes from congruent stimuli (e.g., HI/high pitch) classified faster than attributes from incongruent stimuli (e.g., HI/low pitch). These results differ from those obtained previously with noncorresponding pairs of linguistic-nonlinguistic dimensions. The results also differ from those obtained with traditional Stroop dimensions (colors and color words; Experiment 6), which showed minimal Garner interference and diminishing congruity effects across blocks of trials. We conclude that the interactions found here represent cross-talk between channels within a semantic level of processing. We contrast our view with current models of dimensional interaction. PMID- 2233264 TI - The effect of context on discrimination and bias in recognition memory for pictures and words. AB - When the context accompanying a to-be-remembered word is changed between study and test, recognition memory is impaired. The deleterious effect of context change on recognition memory can be viewed as support for encoding specificity theory, semantic theory, or the existence of two bases for recognition. A fourth possible interpretation, examined here, is that the effect of context change on recognition memory is due to an accompanying change in response bias, rather than a "true" decrease in sensitivity to old and new items. In two experiments, the effect of context change on discrimination and bias in recognition of simple line drawings and their names was examined. Bias was measured using two measures shown by Snodgrass and Corwin (1988) to be theoretically independent of their associated discrimination measures. Context change produced marked conservatism in response bias in both experiments but demonstrated an effect on discrimination in the second experiment only. The shift from a neutral to a conservative response strategy as a result of context change may also be seen in other experiments, in which the same experimental paradigm was used with a variety of stimulus materials. We suggest that the major effect of context manipulation is to produce a change in bias. A stimulus in a familiar environment appears to be more familiar than a stimulus in a strange environment, regardless of its old/new status. In addition, there appears to be a true decrease in discrimination with context change, but this is more difficult to detect. The finding that pictures, which are less polysemous than words, are as affected by context change as words are supports encoding specificity theory over semantic theory. PMID- 2233265 TI - The relation between syllable number and visual complexity in the acquisition of word meanings. AB - Four experiments were conducted to explore the correlation between syllable number and visual complexity in the acquisition of novel words. In the first experiment, adult English speakers invented nonsense words as names for random polygons differing in visual complexity. Visually simple polygons received names containing fewer syllables than visually complex polygons did. In addition, analyses of English word-object pairings indicated that a significant correlation between syllable number and visual complexity exists in the English lexicon. In Experiments 2 and 3, adult English speakers matched monosyllabic novel words more often than trisyllabic novel words with visually simple objects, whereas trisyllabic matches were more common for visually complex objects. Experiment 4 replicated these findings with children, indicating that the assumption of a correlation between word and visual complexity exists during the period of intense vocabulary growth. Although the actual correlation between syllable number and visual complexity is small, other posited constraints on word meaning are also limited in strength. However, an increasing number of small, language specific word-meaning correlations are being uncovered. Given the documented ability of speakers to detect and use these subtle correlations, we argue that a more fruitful approach to word-meaning acquisition would forgo the search for a few broad, powerful word-meaning constraints, and we attempt to uncover individually weak, but perhaps jointly powerful word-meaning correspondences. PMID- 2233266 TI - Cue interaction in human contingency judgment. AB - Most studies of human contingency judgment have been based on the assumption that frequency information about one predictor is assessed in isolation of information about other predictors. Recent evidence, however, suggests that the judged predictive strength of one cue is influenced by the predictive strengths of other copresent cues. Two experiments demonstrate that stimuli with the same outcome contingencies may nonetheless have different predictive strengths as the result of cue interaction. The first experiment, in which a within-subject design was used, provides a demonstration of blocking. A stimulus presented in compound with a strong predictor was rated as less predictive than another stimulus that was presented in compound with a nonpredictive cue. In the second experiment, cue interactions in conditioned inhibition were examined. A stimulus gained negative predictive strength as the result of compound presentations with a positive predictor when the outcome was not presented. This negative predictor was compared with an otherwise analogous stimulus that was not presented in compound with a positive predictor. These results support the use of animal-conditioning models as accounts of human contingency learning. PMID- 2233268 TI - The effect of apparent movement on mental rotation. AB - Eleven subjects were timed as they judged whether a small bar perpendicular to one side of a clockhand would point left or right if the hand was pointing upward (i.e., at the "12 o'clock" position). The clockhand was shown in two successive orientations 30 degrees apart, so that it was perceived to jump from one to the other in either a clockwise or a counterclockwise direction. Reaction times were consistent with the interpretation that the subjects "mentally rotated" the clockhand from its perceived orientation back to the upright before making their decisions. The direction of the jump influenced perceived orientation but did not influence either the direction or rate of mental rotation itself. PMID- 2233267 TI - Sex differences in visual-spatial ability: the role of performance factors. AB - Two studies were designed to explore the role of performance factors as sources of the frequently noted higher male scores on visual-spatial ability tests. In the first study, the mental rotations test (MRT) was administered to male and female college students of equally high quantitative ability (based on SAT math scores). Although males had significantly more correct responses on the test than did females, their advantage was eliminated when the ratio of correct responses to items attempted was used as the dependent measure. In the second study, the same test was administered to new groups of male and female college students. In this sample, the males had significantly higher SAT math scores. The MRT was administered under standard, timed conditions and under untimed conditions. Both raw and ratio scores were calculated. With SAT math score as the covariate, analyses of covariance indicated that males demonstrated higher performance in the timed, raw-score condition but not in the untimed or in the ratio-score conditions. The theoretical and social policy implications of these studies are discussed. PMID- 2233269 TI - Patient care episodes in mental health organizations, United States: selected years between 1955 and 1986. AB - The 4,747 mental health organizations (excluding territories) providing mental health services in the United States during 1986 generated almost 7.9 million patient care episodes including those in Veterans Administration outpatient and partial care programs. However, in order to make comparisons between 1986 data and all years dating back to 1955, outpatient and partial care programs administered by the Veterans Administration (VA) are omitted. Thus the 7.5 million patient care episodes (exclusive of the aforementioned VA programs) represented a more than four-fold increase over the 1.7 million patient care episodes in mental health organizations observed 31 years earlier in 1955. The major shifts in patient care episodes over the 1955-1986 period 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 were inpatient care episodes, and the remaining 23 percent were outpatient episodes; by 1986, inpatient care episodes constituted only 27 percent of the total, while 68 percent were outpatient episodes, and 5 percent were partial care episodes. Moreover, between 1955 and 1986, the primary locus of inpatient care episodes shifted from State and county mental hospitals to non-Federal general hospitals, and by 1986 over one-half of the outpatient care episodes and about two-thirds of the partial care episodes occurred in the multiservice mental health organizations. PMID- 2233270 TI - Fluoride stimulates [3H]thymidine incorporation and alkaline phosphatase production by human osteoblasts. AB - The effect of sodium fluoride on alkaline phosphatase (ALP) release and [3H]thymidine uptake by human osteoblasts in culture was investigated. Sodium fluoride stimulated both ALP release and [3H]thymidine uptake at concentrations of sodium fluoride greater than 250 mumol/L. This stimulation was similar in magnitude to that induced by 1,25-dihydroxycholecalciferol. The fluoride-induced increase in ALP was inhibited by verapamil, a calcium channel blocker. We conclude that sodium fluoride stimulates osteoblasts to proliferate and to release ALP. This stimulation by fluoride is dependent on calcium influx. Fluoride-induced stimulation of human osteoblasts may be relevant to its effect in enhancing bone formation in patients with osteoporosis. PMID- 2233271 TI - Time-dependent variations in bone turnover parameters during 2 months' cyclic treatment with different doses of combined estrogen and progestogen in postmenopausal women. AB - We determined the time-dependent variations in biochemical estimates of bone resorption and bone formation in 30 healthy postmenopausal women treated for two consecutive cycles of 28 days with a sequential estrogen/gestagen therapy. The women received either 1, 2, or 4 mg estradiol (E2) for 22 days and 1 mg norethisterone acetate (NETA) from day 13 to 22 of each cycle. Blood samples were drawn twice a week, ie, 16 blood samples in each woman. Biochemical estimates of bone resorption (fasting urinary hydroxyproline/creatinine, fasting urinary calcium/creatinine) decreased significantly during the two treatment cycles. In contrast, there was no overall decrease in bone formation parameters (plasma bone Gla protein [pBGP], serum alkaline phosphatase), and serum alkaline phosphatase decreased significantly during the estrogen-only phase, but increased during the E2 plus NETA phase. The present study supports our previous suggestion that NETA stimulates bone formation in early postmenopausal women. PMID- 2233272 TI - Repeated pregnancy without lactation: effects on maternal glycemic control, pregnancy outcome, carcass composition, and fat distribution in rats. AB - Repeated pregnancy without lactation in rats has been reported to produce permanently elevated carcass fat mass and hyperplasia in subcutaneous fat depot. In the present study, the pregnancy outcome, intravenous glucose tolerance ability (IVGTT), and carcass composition were further examined in Osborne-Mendel rats. Female rats were divided into pregnancy-lactation (PL), pregnancy-no lactation (PNL), and control (CON) groups. Half of the rats were killed after three pregnancy/lactation cycles, whereas the rest were given a 12-week rest period before killing. It was found that rats in PNL group had fasting hyperglycemia and insulin insensitivity during the third pregnancy (P less than or equal to .05), elevated spontaneous abortion rate (P less than or equal to .05), and elevated subcutaneous fat content (P less than or equal to .01) relative to that of PL rats or CON rats. After a 12-week rest period, a significant increase in subcutaneous fat cell number was also observed in PNL rats. PL rats, on the other hand, have significantly elevated internal/subcutaneous fat ratios (P less than or equal to .05), both immediately after weaning and after the 12-week rest period. The significance of this change is not yet known. PMID- 2233273 TI - Sources of propionate in inborn errors of propionate metabolism. AB - Amino acids are widely regarded as the most important sources of propionate in disorders of propionate metabolism. Propionate production was measured in the fasting state by continuous infusion of sodium [1-13C]propionate in three children with methylmalonic acidemia (MMA) and three with propionic acidemia (PA). The contribution of isoleucine, valine, threonine, and methionine catabolism to total propionate production was estimated by extrapolation from the hydroxylation of phenylalanine determined by a continuous-infusion [2H5]phenylalanine technique. The contribution of gut bacterial propionate production was determined by measuring total propionate production before and after treatment with oral metronidazole (10 to 20 mg/kg/d for 1 week). Amino acid catabolism accounted for a mean of 51.7% (range, 24.5% to 66.4%) of total propionate production. The mean decrease in propionate production after metronidazole was 22.2% +/- 8.5 (P less than .02); this percentage is likely to represent the minimum propionate production attributable to gut bacteria. Approximately 30% of total propionate production was unaccounted for, and is likely to arise primarily from odd-chain fatty acid catabolism in the fasting state. These results indicate that sources of propionate other than from protein catabolism are important in disorders of propionate metabolism, and explain the generally disappointing response to dietary protein restriction. PMID- 2233274 TI - Counterregulatory response to insulin-induced hypoglycemia in trained and nontrained humans. AB - The aim of the present series of experiments was to investigate the hormonal counterregulatory response to insulin-induced hypoglycemia in trained and nontrained healthy individuals. Five endurance athletes and six controls were administered intravenous insulin infusion at a rate of 0.15 U/kg/h until plasma glucose reached 50 mg/dL. The mean duration of the infusion in the trained and nontrained subjects corresponded to 18.6 and 26.3 minutes (P less than .01), suggesting that the former were characterized by an increased insulin sensitivity. Plasma glucose levels were similar in the two groups at the end of the insulin infusion, as well as during the postinfusion recovery period. Forty five minutes after the end of the infusion, plasma glucose levels were not significantly different from the preinfusion levels in the two groups. During this period of glycemia recovery, the increases in plasma glucagon, epinephrine, norepinephrine, and growth hormone were at least 50% lower in the trained than in the nontrained subjects. The increase in heart rate and oxygen uptake during the same period of time was significantly higher in the trained subjects. To determine whether this reduced hormonal response to hypoglycemia was due to reduced insulin levels or to an increased sensitivity to counterregulatory hormones, we investigated the effect of epinephrine on plasma glucose in two other groups of trained and nontrained subjects. In response to a constant epinephrine infusion of 0.01 or 0.1 micrograms/kg fat-free mass (FFM)/min, plasma glucose levels increased similarly in the two groups. In conclusion, these results indicate that trained subjects are characterized by a normal recovery from hypoglycemia despite a reduced response of counterregulatory factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233275 TI - Aging bone loss from the femur, spine, radius, and total skeleton. AB - In order to establish a comprehensive model for involutional bone loss, the following measurements were made of healthy white women: total body calcium by neutron activation analysis, bone density of the distal radius by single-photon absorptiometry, and dual-photon absorptiometry of the lumbar spine and femur (neck, Ward's triangle, and intertrochanteric areas). Longitudinal measurements were made for each of these skeletal sites except the femur. Evidence for a curvilinear component to the pattern of bone loss with aging was found for total body calcium and bone density of the radius, but not for the other measurements on analysis of cross-sectional data. Longitudinal studies confirmed that substantial bone loss begins only after menopause for the radius, whereas there is substantial premenopausal loss of bone from the lumbar spine. Prevention of vertebral osteoporosis requires maximizing bone mass before menopause. If longitudinal data confirm the model of linear rates of bone loss for the femur, there will be important implications for prevention of hip fractures. PMID- 2233276 TI - Altered ketone body metabolism during gram-negative sepsis in the rat. AB - To investigate why blood ketone bodies are depressed during sepsis, the production and utilization of ketone bodies was studied in fasted control, fasted, Escherichia coli-treated, fed control, and fed E coli-treated rats. Gram negative sepsis was induced by intravenous (IV) injection of 8 x 10(7) live colonies of E coli per 100 g body weight. Food was removed from the fasted rats after E coli injection. Fed rats were infused intragastrically with a nutritionally adequate diet for 5 days before inducing sepsis. Twenty-four hours after E coli injection, blood ketone bodies were reduced in fasted septic rats and fed septic rats compared with their respective control rats. Ketogenesis and oxidation of labeled palmitate was not altered in hepatocytes from fasted E coli treated rats. Yet, ketogenesis declined significantly in hepatocytes from fed E coli-treated rats. Oxidation of labeled palmitate was also significantly reduced in hepatocytes from fed E coli-treated rats. Utilization of ketone bodies as measured by the incorporation of [3-14C]beta-hydroxybutyrate into CO2, increased over threefold in the diaphragm, 12% in the heart, and 19% in the kidneys from the fasted E coli-treated rats. In the fed state, incorporation of [3-14C]beta hydroxybutyrate into CO2 was elevated fivefold in the heart, fourfold in the diaphragm, and over threefold in the kidneys from the septic rats. These results suggest that in the fasted state, plasma ketone bodies remain low during gram negative sepsis because peripheral tissues use more ketone bodies and because liver ketogenesis is not increased to compensate for the increased utilization. In the fed state, the reduction in blood ketone bodies appears to be attributed to both impaired ketogenic capacity and increased peripheral utilization. PMID- 2233277 TI - Unique alterations of neuropeptide content in median eminence, amygdala, and dorsal vagal complex of 3- and 6-week-old diabetes mutant mice. AB - The nature of the genetic defects which define the obese (ob) and diabetes (db) loci in mice remain unknown, but both produce similar syndromes when maintained in the same strain of mice. There is some evidence suggesting a lesion in the central nervous system (CNS) in db/db mice, while ob/ob mice appear to have a primary lesion outside the CNS. In a search for further evidence of a unique central lesion in db/db mice, we have examined neuropeptide content in selected, microdissected brain areas in both of these mutants and lean controls. In order to rule out possible interactions of the db mutation with the genetic background, diabetes mice of both C57BL/KsJ and C57BL/6J strains were studied. When concentrations of nine neuropeptide immunoreactivities were examined in up to seven microdissected areas of the brain, C57BL/6J ob/ob mice showed only one reproducible alteration, a lower content of beta-endorphin-like immunoreactivity (LI) in the preoptic area at both 3 and 6 weeks of age as compared with lean littermates. In contrast, db/db mice of both C57BL/6J and C57BL/KsJ strains exhibited alterations in a total of four peptides in three brain areas: lower concentration of somatostatin-LI in median eminence, higher Met-enkephalin-LI in dorsal vagal complex of the medulla oblongata, higher substance P-LI and lower vasoactive intestinal polypeptide (VIP)-LI in amygdala. The concentrations of the peptides studied in medial basal hypothalamus, lateral hypothalamus, substantia nigra, and preoptic area were not reproducibly altered in db/db mice. These data provide preliminary evidence for unique brain abnormalities in db/db mice in specific areas that are involved in processing of neural signals that can affect the islets of Langerhans, gonadotrophin secretory patterns, and many other visceral functions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233278 TI - Collagen synthesis in postmenopausal women during therapy with anabolic steroid or female sex hormones. AB - The effect of anabolic steroid therapy and estrogen-progestogen substitution therapy on serum concentration of procollagen type III aminoterminal peptide (PIIINP), a measure of collagen synthesis, in postmenopausal women was studied in two double-blind studies: (1) 39 women allocated to treatment with either 50 mg nandrolone decanoate as an intramuscular depot or placebo injections every third week for 1 year, and (2) 40 women allocated to receive either 2 mg 17 beta estradiol plus 1 mg norethisterone acetate daily or placebo tablets for 1 year. Serum PIIINP was measured every 3 months during the study. Anabolic steroid therapy resulted in a more than 50% increase (P less than .001) in serum PIIINP at 3 months, which thereafter decayed but remained significantly increased throughout the study period. Serum PIIINP showed the same pattern during estrogen progestogen therapy, but to a lesser degree. We conclude that anabolic steroids stimulate type III collagen synthesis in postmenopausal women, while estrogen progestogen therapy may have such an effect, but only to a lesser degree. PMID- 2233279 TI - Protein kinase C inhibitors block insulin and PMA-stimulated hexose transport in isolated rat adipocytes and BC3H-1 myocytes. AB - Effects of protein kinase C (PKC) inhibitors and "down-regulation" on insulin and PMA-stimulated 2-deoxyglucose transport were determined in isolated rat adipocytes or BC3H-1 myocytes. In both model systems, H-7, sangivamycin, and staurosporine, inhibitors of the catalytic domain of PKC, each effectively blocked insulin and PMA-stimulated hexose uptake at similar concentrations. In the myocytes, staurosporine completely blocked the insulin effect retained post chronic phorbol myristate acetate (PMA)-induced "down-regulation." These findings indicate (1) that chronic pretreatment with PMA may not lead to a complete loss of PKC activity in the myocyte, and (2) that PKC is involved in insulin stimulated hexose transport in both isolated rat adipocytes and BC3H-1 myocytes. PMID- 2233280 TI - Increased resting energy expenditure in human immunodeficiency virus-infected men. AB - Even in the absence of anorexia and malabsorption, weight loss is frequently observed in patients with acquired immunodeficiency syndrome (AIDS) or AIDS related complex (ARC). To investigate whether increased resting energy expenditure (REE) might be responsible for this weight loss, indirect calorimetry was performed in 18 human immunodeficiency virus (HIV)-infected men free of clinically active opportunistic infections for at least 2 months. Patients with AIDS (n = 11) or ARC (n = 7) had 9% higher rates of REE when compared with 11 healthy volunteers (P less than .05) with similar food intake and of the same body composition. The results obtained from patients with AIDS or ARC were identical. As no differences were found between patients and controls in plasma concentrations of catecholamines, thyroid hormones, cortisol, or tumor necrosis factor, except for lower concentrations of norepinephrine in the patients (mean +/- SD, 233 +/- 111 v 367 +/- 125 ng/L, patients v controls, P less than .01), this hypermetabolism is not explained by higher levels of these catabolic hormones. The results indicate that even in the absence of acute concomitant infections, increased REE may contribute to the weight loss in patients with AIDS or ARC. PMID- 2233281 TI - Early signs of vascular disease in homocystinuria: a noninvasive study by ultrasound methods in eight families with cystathionine-beta-synthase deficiency. AB - Fourteen patients (six males, eight females; mean age, 20 years) with homocystinuria due to homozygous cystathionine-beta-synthase (CBS) deficiency, underwent a vascular examination. Fourteen heterozygotes (seven males, seven females; mean age, 46 years), including 12 parents and one daughter of homozygotes (obligate heterozygotes), and one sister of a homozygote (with low enzyme activity as evaluated in vitro), were also examined. Homozygotes and heterozygotes were compared with two separate control groups of different age (mean age, 20 and 43 years, respectively). Ankle/arm systolic pressure index (by continuous-wave Doppler) was, on average, lower in homozygotes (P less than .01) and heterozygotes (P less than .05) as compared with the controls. An ankle/arm index less than 0.97 and suggesting flow-reducing arterial lesions was found in six (21%) lower limbs of homozygotes versus zero in controls (P less than .05). Echo Doppler (Duplex Scanner) abnormalities, indicating early, non-flow-reducing lesions of iliac arteries were more frequent in homozygotes (seven wall abnormalities or stenoses less than 15%) than in young controls (P less than .05). The corresponding figures for heterozygotes were seven wall abnormalities or stenoses (1% to 15% and one stenosis 16% to 50%) (P less than .01 v middle aged controls). Early lesions (three wall abnormalities or stenoses less than 15%, three stenoses 16% to 50%) were detected in six (23%) internal carotids of heterozygotes versus three (3%) of corresponding controls (P less than .05). Technical limitations precluded the accurate detection of early lesions in the internal carotid arteries of young homozygotes and controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233282 TI - Type III hyperlipoproteinemia in a child with hemolytic uremic syndrome. AB - The case of a 6-year-old girl with severe hyperlipoproteinemia and chronic renal failure that developed after hemolytic uremic syndrome (HUS) is reported. The patient was homozygous for apolipoprotein (apo) E2, and her very-low-density lipoprotein (VLDL)-cholesterol/serum-triglyceride (TG) ratio of 0.63 was unusually high. She was consistently diagnosed to have type III hyperlipoproteinemia (HLP). This is the first report of type III HLP in a child with chronic renal disease. PMID- 2233283 TI - Bioavailability of phenylalanine and aspartate from aspartame (20 mg/kg) in capsules and solution. AB - Aspartame (L-aspartyl-L-phenylalanine methyl ester) was given in capsules or solution to compare the bioavailability of its constituent amino acids, aspartate and phenylalanine. Twenty healthy subjects received a single 20 mg/kg dose of aspartame in capsules or solution in a randomized, crossover design. Plasma amino acid concentrations and the phenylalanine to large neutral amino acid ratios (Phe/LNAA) were determined. Plasma aspartate concentrations did not increase with either treatment. For plasma phenylalanine following capsule ingestion, there was a smaller peak plasma concentration (Cmax; 103.3 v 126.6 mumol/L), a longer time to peak concentration (tmax; 108.6 v 36.6 minutes), but no significant difference in the area under the plasma concentration-time curve (AUC) (7,656 v 7,200 mumol.min/L) when compared with solution ingestion. The maximum plasma Phe/LNAA ratio was smaller (0.16 v 0.19) with capsules. The changes for plasma tyrosine were similar to those seen with phenylalanine. There were no significant differences in the plasma concentrations of the other LNAAs between capsule and solution ingestion. Thus, given the small effect on phenylalanine Cmax and Phe/LNAA and no effect on the extent of absorption of phenylalanine, aspartame ingested in capsules at doses up to 20 mg/kg is a suitable dosage form for blinded clinical studies, provided that the slower rate of absorption of phenylalanine from capsules is taken into account. PMID- 2233284 TI - Influence of cold exposure on plasma triglyceride clearance in humans. AB - Recent human studies have shown that cold exposure increases lipid oxidation, even when the oxidation of circulating free fatty acid (FFA) is markedly reduced by the ingestion of nicotinic acid, thus seriously questioning the importance of FFA for lipid oxidation in the cold-exposed humans. It was therefore hypothesized that similarly to prolonged exercise, fatty acids from plasma triglycerides (TG) are important energy substrates for oxidation during prolonged cold exposure in man. The goal of this study was to determine the influence of cold exposure on an index of plasma TG utilization, the intravenous fat tolerance test (IVFTT). To evaluate the possibility of a delayed increase in fat tolerance, a second cold exposure and an IVFTT were also performed 24 hours after the first cold exposure. Seven healthy males (fasting, seminude) were subjected to an IVFTT (1 mL/kg 10% Intralipid) on three occasions while resting for 160 minutes: (1) at 29 degrees C, (2) in the cold (10 degrees C, 1 m/s wind), and (3) at 10 degrees C 24 hours after the first cold test. One week separated the warm test from the cold tests. Cold exposure reduced mean body temperature by 3.4 +/- 0.1 degree C and increased energy expenditure 2.5 times in comparison to warm values (P less than .01). It also increased fat oxidation by 70% (P less than .05) and plasma glycerol levels (P less than .05), but did not alter fat tolerance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233285 TI - Methods in enzymology. Cumulative subject index. PMID- 2233286 TI - Oxygen radicals in biological systems. Part B: Oxygen radicals and antioxidants. PMID- 2233287 TI - Free radical initiators as source of water- or lipid-soluble peroxyl radicals. PMID- 2233288 TI - Generation of iron(IV) and iron(V) complexes in aqueous solutions. PMID- 2233289 TI - Use of ascorbate as test for catalytic metals in simple buffers. PMID- 2233290 TI - Detection of singlet molecular oxygen during chloride peroxidase-catalyzed decomposition of ethyl hydroperoxide. PMID- 2233291 TI - Determination of hydroperoxides with fluorometric reagent diphenyl-1 pyrenylphosphine. PMID- 2233292 TI - Phycoerythrin fluorescence-based assay for reactive oxygen species. PMID- 2233293 TI - Determination of superoxide dismutase activity by purely chemical system based on NAD(P)H oxidation. PMID- 2233294 TI - Assay for superoxide dismutase based on chemiluminescence of luciferin analog. PMID- 2233295 TI - Automated assay of superoxide dismutase in blood. PMID- 2233296 TI - Assay of superoxide dismutase applicable to whole bacterial cells. PMID- 2233297 TI - Superoxide dismutase mimic prepared from desferrioxamine and manganese dioxide. PMID- 2233298 TI - Analysis of extracellular superoxide dismutase in tissue homogenates and extracellular fluids. PMID- 2233299 TI - Assays for cytochrome P-450 peroxygenase activity. PMID- 2233300 TI - Reductive cleavage of hydroperoxides by cytochrome P-450. PMID- 2233301 TI - DT-diaphorase: purification, properties, and function. PMID- 2233302 TI - Antioxidant activities of bile pigments: biliverdin and bilirubin. PMID- 2233303 TI - Fluorescence measurements of incorporation and hydrolysis of tocopherol and tocopheryl esters in biomembranes. PMID- 2233304 TI - Assay of lipid hydroperoxides using high-performance liquid chromatography with isoluminal chemiluminescence detection. PMID- 2233305 TI - Determination of methyl linoleate hydroperoxides by 13C nuclear magnetic resonance spectroscopy. PMID- 2233306 TI - Gas chromatography-mass spectrometry assays for lipid peroxides. PMID- 2233307 TI - Gas chromatography-mass spectrometry of 4-hydroxynonenal in tissues. PMID- 2233308 TI - Determination of aldehydic lipid peroxidation products: malonaldehyde and 4 hydroxynonenal. PMID- 2233309 TI - Malondialdehyde determination as index of lipid peroxidation. PMID- 2233310 TI - Cholesterol epoxides: formation and measurement. PMID- 2233311 TI - Oxystat technique in study of reactive oxygen species. PMID- 2233313 TI - Iron redox reactions and lipid peroxidation. PMID- 2233312 TI - Phospholipid hydroperoxide glutathione peroxidase. PMID- 2233314 TI - Protein that prevents mercaptan-mediated protein oxidation. PMID- 2233316 TI - Photodynamic methods for oxy radical-induced DNA damage. PMID- 2233315 TI - Protein degradation as an index of oxidative stress. PMID- 2233317 TI - In vivo oxidative DNA damage: measurement of 8-hydroxy-2'-deoxyguanosine in DNA and urine by high-performance liquid chromatography with electrochemical detection. AB - HPLC with electrochemical detection is a highly sensitive and selective method for detecting the oxidatively modified DNA residue oh8dG. By this method, the detection of oh8dG from DNA and urine offers a powerful approach for assessing in vivo oxidative damage. Application of this technique to the detection of oh8dG from DNA permits the quantitation of the steady-state levels of this oxidatively modified deoxynucleoside and overcomes the detection problems associated with the extremely low levels present in DNA. In addition, the selectivity gained by this detection method eliminates the problem of separating the signal for oh8dG from normal deoxynucleosides. The quantitation of oh8dG in urine complements the measurement of oh8dG in DNA by estimating cumulative oxidative DNA damage in the body. In addition, the urinary assay provides a noninvasive means of measuring this type of damage in laboratory animals and human populations. Thus, an individual animal or human subject may be monitored over time, possibly under various prooxidant conditions, using oh8dG as a sensitive marker for oxidative DNA damage. This analytical approach may allow one to estimate the exposure of an individual to prooxidant conditions associated with lifestyle, genetic predisposition, degenerative diseases, and environmental toxins. PMID- 2233318 TI - Fluorometric analysis of DNA unwinding to study strand breaks and repair in mammalian cells. PMID- 2233320 TI - Measurement of oxidized proteins in systems involving activated neutrophils or HL 60 cells. PMID- 2233319 TI - Clastogenic factors: detection and assay. PMID- 2233321 TI - Visible-range low-level chemiluminescence in biological systems. PMID- 2233322 TI - Modulation of cellular glutathione and protein thiol status during quinone metabolism. PMID- 2233323 TI - Measurement of xanthine oxidase in biological tissues. PMID- 2233324 TI - Oxy radicals in disseminated intravascular coagulation. PMID- 2233325 TI - Oxy radicals in endotoxin shock. PMID- 2233326 TI - Biochemical pharmacology of inflammatory liver injury in mice. PMID- 2233327 TI - Measurement of oxidant stress in vivo. PMID- 2233328 TI - Oxygen-derived free radicals in reperfusion injury. PMID- 2233329 TI - Noninvasive fluorometric measurement of mitochondrial membrane potential in isolated working rat hearts during ischemia and reperfusion. PMID- 2233330 TI - Oxygen scavengers in myocardial preservation during transplantation. PMID- 2233331 TI - Quantitation of free radical-mediated reperfusion injury in renal transplantation. PMID- 2233334 TI - Arachidonate related lipid mediators. PMID- 2233333 TI - Use of perfused organs in measurement of drug-induced oxidant stress. PMID- 2233332 TI - Use of isolated perfused organs in hypoxia and ischemia/reperfusion oxidant stress. PMID- 2233335 TI - Nomenclature. PMID- 2233336 TI - Bioassay of paf-acether by rabbit platelet aggregation. PMID- 2233337 TI - Electron-capture negative-ion chemical ionization mass spectrometry of lipid mediators. PMID- 2233338 TI - Bioassay of platelet-activating factor by release of [3H]serotonin. PMID- 2233339 TI - Quantitation of platelet-activating factor by gas chromatography-mass spectrometry. PMID- 2233340 TI - Quantitative analysis of platelet-activating factor by gas chromatography negative-ion chemical ionization mass spectrometry. PMID- 2233341 TI - Isolation of platelet-activating factor and purification by thin-layer chromatography. AB - Isolation and purification of platelet-activating factor can be accomplished with reasonable ease and effectiveness given the precautions and suggestions outlined above. These experimental approaches represent a composite of those practiced in the author's laboratory combined with selected observations reported in the literature. PMID- 2233343 TI - High-performance liquid chromatography separation and determination of lipoxins. PMID- 2233342 TI - Separation and characterization of arachidonate-containing phosphoglycerides. PMID- 2233344 TI - Quantitation of epoxy- and dihydroxyeicosatrienoic acids by stable isotope dilution mass spectrometry. PMID- 2233345 TI - High-performance liquid chromatography for chiral analysis of eicosanoids. PMID- 2233347 TI - Enzyme immunoassays of eicosanoids using acetylcholinesterase. PMID- 2233346 TI - Extraction of phospholipids and analysis of phospholipid molecular species. PMID- 2233349 TI - Purification of arachidonate 5-lipoxygenase from potato tubers. PMID- 2233348 TI - Preparation of prostaglandin H2: extended purification/analysis scheme. PMID- 2233351 TI - Immunoaffinity purification of arachidonate 5-lipoxygenase from porcine leukocytes. PMID- 2233350 TI - Potato arachidonate 5-lipoxygenase: purification, characterization, and preparation of 5(S)-hydroperoxyeicosatetraenoic acid. PMID- 2233353 TI - Synthesis of epoxyeicosatrienoic acids and heteroatom analogs. PMID- 2233352 TI - Radioimmunoassay of 11-dehydrothromboxane B2. PMID- 2233354 TI - Isolation of rabbit renomedullary cells and arachidonate metabolism. PMID- 2233355 TI - Cytochrome P-450 arachidonate oxygenase. PMID- 2233356 TI - Measurement of thromboxane metabolites by gas chromatography-mass spectrometry. PMID- 2233357 TI - Use of WEB 2086 and WEB 2170 as platelet-activating factor antagonists. PMID- 2233359 TI - Culture of bone marrow-derived mast cells: a model for studying oxidative metabolism of arachidonic acid and synthesis of other molecules derived from membrane phospholipids. PMID- 2233358 TI - Cloning of leukotriene A4 hydrolase cDNA. PMID- 2233360 TI - Endothelial cells for studies of platelet-activating factor and arachidonate metabolites. PMID- 2233361 TI - Use of cultured cells to study arachidonic acid metabolism. PMID- 2233362 TI - Eicosanoid biochemistry in cultured glomerular mesangial cells. PMID- 2233363 TI - Interaction between platelets and lymphocytes in biosynthesis of prostacyclin. PMID- 2233364 TI - Eicosanoid interactions between platelets, endothelial cells, and neutrophils. PMID- 2233365 TI - Isolated perfused rat lung in arachidonate studies. PMID- 2233367 TI - Immunoaffinity purification-chromatographic quantitative analysis of arachidonic acid metabolites. PMID- 2233366 TI - Isolated coronary-perfused mammalian heart: assessment of eicosanoid and platelet activating factor release and effects. PMID- 2233368 TI - Preparation of human and animal lung tissue for eicosanoid research. PMID- 2233369 TI - Preparation of tetradeuterated leukotriene A4 methyl ester: methyl-[11,12,14,15 2H4]-(5S,6S)-oxido-(7E,9E,11Z, 14Z)-eicosatetraenoat e. PMID- 2233370 TI - Quantitation of sulfidopeptide leukotrienes in biological fluids by gas chromatography-mass spectrometry. PMID- 2233371 TI - Standardization and validation of medical decision-support systems: the CSE project. PMID- 2233373 TI - A brief history of computer-assisted electrocardiography. AB - This paper reviews the history of the development of computer methods for ECG interpretation. Selected highlights are presented which indicate how technological advances have paralleled the growth of the application of the technique to a point where globally over 100 million ECGs per annum are now interpreted by computer. PMID- 2233372 TI - Common standards for quantitative electrocardiography: goals and main results. CSE Working Party. AB - Computer processing of electrocardiograms (ECGs) has over the last 15 years increased rapidly. Still, there are at present no standards for computer ECG interpretation. Different techniques are used not only for measurement and interpretation, but also for transmission and storage of data. In order to fill these gaps, a large international project, sponsored by the European Commission, was launched in 1980 to develop "Common Standards for Quantitative Electrocardiography (CSE)". The main objective of the first CSE study was to reduce the wide variation in wave measurements currently obtained by ECG computer programs. The second study was started in 1985 and aimed at the assessment and improvement of diagnostic classification of ECG interpretation programs. To this end reference libraries of well documented ECGs have been developed and comprehensive reviewing schemes devised for the visual and computer analysis of ECGs. This task was performed by a board of cardiologists in a Delphi review process, and by 9 VCG and 10 standard 12-lead programs developed by university research groups and by industry. A third action was started in June 1989 to harmonize acquisition, encoding, interchange and storing of digital ECG data. The action thus performed have become internationally recognized milestones for the standardization of quantitative electrocardiography. PMID- 2233374 TI - The role of computer modeling in electrocardiography. AB - This paper introduces some levels at which the computer has been incorporated in the research into the basis of electrocardiography. The emphasis lies on the modeling of the heart as an electrical current generator and of the properties of the body as a volume conductor, both playing a major role in the shaping of the electrocardiographic waveforms recorded at the body surface. It is claimed that the Forward-Problem of electrocardiography is no longer a problem. Several source models of cardiac electrical activity are considered, one of which can be directly interpreted in terms of the underlying electrophysiology (the depolarization sequence of the ventricles). The importance of using tailored rather than textbook geometry in inverse procedures is stressed. PMID- 2233375 TI - Reference standards for software evaluation. AB - The field of automated ECG analysis was one of the earliest topics in Medical Informatics and may be regarded as a model both for computer-assisted medical diagnosis and for evaluating medical diagnostic programs. The CSE project has set reference standards of two kinds: In a broad sense, a standard how to perform a comprehensive evaluation study, in a narrow sense, standards as specific references for evaluating computer ECG programs. The evaluation methodology used within the CSE project is described as a basis for presentation of results which are published elsewhere in this issue. PMID- 2233376 TI - Evaluation of ECG interpretation systems: signal analysis. AB - Performance analysis of biosignal processing systems which provide diagnostic statements requires particular care. Besides general accuracy requirements, psychological and legal implications for patient and physician have to be considered on both the development and the user sites. Cybernetics and control engineering have provided the basic methodology for performance analysis of systems: in technical systems often mathematically defined functions and signals can be fed into the system to be tested and its response and output provide the necessary performance characteristics after adequate mathematical analysis. For systems which process biosignals, as for example ECG analysis systems, instead of analytically given signals learning and test sets of data derived from patients have to be applied. The performance analysis is done on a statistical basis. In this paper construction and composition of learning and test data sets as well as methods for performance evaluation of the signal processing part of ECG programs are described. Specific reference is made to the European project Common Standards for Quantitative Electrocardiography (CSE) where ten ECG- and nine VCG programs have been tested. The results of these tests provide reference data and standards for further program development as well as for independent system performance evaluation. PMID- 2233377 TI - Evaluation of ECG interpretation results obtained by computer and cardiologists. AB - In an international project investigators from 25 institutes are trying to establish a common reference library and evaluation methods for testing the diagnostic performance of various ECG computer programs and of cardiologists, based on ECG-independent clinical information. A first set of 500 validated ECGs was collected and analyzed by fifteen different computer programs and nine cardiologists, seven of who analysed the ECG and five the VCG. A coding scheme was used to map individual diagnostic statements onto a common set. Combined program and referee results were obtained by weighted averaging. Preliminary results indicate that the classification accuracy of several programs can still be improved. However, it was also apparent that the results of the best 12-lead ECG computer programs proved to be almost as accurate as the best of seven cardiologists in classifying seven main disease categories, i.e., normal, left, right and biventricular hypertrophy, anterior, inferior and combined myocardial infarction. Evaluation of rhythm statements and conduction disturbances was not included in the study. The data collection is still being pursued in order to reach over 1,000 cases. In this way a common diagnostic database is being established for comparative testing of diagnostic computer programs. This should lead to consumer protection and improve the accuracy and reliability of computerized electrocardiography. PMID- 2233378 TI - Signal analysis for ECG interpretation. AB - In ECG interpretation usually two main areas are discerned: the signal analysis and the diagnostic classification. This article reviews the major developments in the first area. ECG signal analysis itself is subdivided into the stages data acquisition, data transformation, feature selection, and data reduction. These stages are consecutively reviewed, while in the data transformation stage digital filtering, detection, wave typing, beat selection, and boundary recognition are discussed. PMID- 2233379 TI - Classification methods for computerized interpretation of the electrocardiogram. AB - Two methods for diagnostic classification of the electrocardiogram are described: a heuristic one and a statistical one. In the heuristic approach, the cardiologist provides the knowledge to construct a classifier, usually a decision tree. In the statistical approach, probability densities of diagnostic features are estimated from a learning set of ECGs and multivariate techniques are used to attain diagnostic classification. The relative merits of both approaches with respect to criteria selection, comprehensibility, flexibility, combined diseases, and performance are described. Optimization of heuristic classifiers is discussed. It is concluded that heuristic classifiers are more comprehensible than statistical ones; encounter less difficulties in dealing with combined categories; are flexible in the sense that new categories may readily be added or that existing ones may be refined stepwise. Statistical classifiers, on the other hand, are more easily adapted to another operating environment and require less involvement of cardiologists. Further research is needed to establish differences in performance between both methods. In relation to performance testing the issue is raised whether the ECG should be classified using as much prior information as possible, or whether it should be classified on itself, explicitly discarding information other than age and sex, while only afterwards other information will be used to reach a final diagnosis. Consequences of taking one of both positions are discussed. PMID- 2233380 TI - Methodology of ECG interpretation in the AVA program. AB - The AVA program combines a thirty-year history with an approach that remains innovative; namely: multivariate statistical analysis on orthogonal ECG leads. Its diagnostic reference base includes only diagnoses independently verified by non-ECG criteria. The diagnostic module assesses probabilities of nine alternative disease categories, based on QRS-T parameters; or four other categories in case of conduction defects. Probabilities of left or right atrial overload are also computed. The program also recognizes wall injury, T-wave abnormalities, electrolyte disturbances, myocardial ischemia, and makes differential diagnoses between strain and digitalis effects. An arrhythmia classification module can generate any of 40 rhythm statements. Signal recognition is based on the spatial velocity function. The program has been translated to a microcomputer version. PMID- 2233381 TI - Methodology of ECG interpretation in the Nagoya program. AB - The outline of the Nagoya Program, the most representative software package for computerized electrocardiography in Japan, is described. First, the history and current status of research and its transfer to commercial products for computerized interpretation of electrocardiograms is briefly reviewed. Second, development and testing of the Nagoya Program is depicted, referring to a gold standard for evaluation and the database being used for this purpose, and to its participation in the CSE study. Third, a description of signal acquisition and wave identification is given, followed by the detection of rhythm disturbances. Next, algorithms for contour classification, which consist of decision-tree logic established through trial and error and making use of the database of ECGs, are described. Finally, special features and future plans of the Nagoya Program are mentioned. PMID- 2233382 TI - Methodology of the modular ECG analysis system MEANS. AB - The methodology, used in the Modular ECG Analysis System (MEANS) is described. MEANS consists of modules for signal analysis and diagnostic classification. The basic structure of the modular interpretation system remained intact over a period of 20 years, while all modules underwent many changes as a function of experience and insight, and the continuously changing information technology. The article describes the advantages of a modular approach to decision-support systems, the most important ones being easier maintenance of the software package and separate optimization and testing of each module. The overall evaluation of MEANS was done in the CSE study. Evaluation results for modules and for the entire system are presented. PMID- 2233383 TI - Methodology of ECG interpretation in the Glasgow program. AB - This paper describes the methods currently used in Glasgow Royal Infirmary for computer analysis of electrocardiograms. The software is designed to analyse from 3 to 15 simultaneously recorded leads, with facilities for analysis of rhythm and serial changes. Options for Minnesota Code (with serial comparison) and XYZ lead interpretation are available. PMID- 2233384 TI - Methodology of ECG interpretation in the Dalhousie program; NOVACODE ECG classification procedures for clinical trials and population health surveys. AB - The Dalhousie ECG Program was designed specifically for the needs of epidemiologic studies, health surveys, and clinical trials. The program logic is dynamic in that it can accommodate any combination of ECG leads, record length and sampling rate. The NOVACODE module of the program classifies ECGs according to the Minnesota Code, supplemented with new sets of logic criteria for conduction defects, acute myocardial infarction, and serial ECG changes. Improved statistical models are incorporated for enhanced detection of myocardial infarction using the Cardiac Infarction Injury Score, and for quantification of left ventricular mass estimation. It is anticipated that these program improvements will enhance its utility particularly in monitoring progression and regression of cardiac involvement in hypertensive and ischemic heart disease, and in the assessment of the effectiveness of intervention on cardiovascular disease risk factors. PMID- 2233385 TI - Methodology of ECG interpretation in the Hannover program. AB - The Hannover ECG program HES has been designed for measurement and interpretation of resting and (moderate) exercise electrocardiograms. In the signal analysis part the program follows an averaging strategy. For diagnostic classification a hybrid model with decision trees and scoring algorithms, and with multivariate probabilistic tests for derivation of category A statements is applied. The multivariate classification technique allows to adjust sensitivity and specificity for specific application areas without changing the diagnostic criteria. PMID- 2233386 TI - Methodology of ECG interpretation in the Padova program. AB - The main lines of the program designed for the interpretation of ECGs, developed in Padova by LADSEB-CNR with the cooperation of the Medical School of the University of Padova are described. In particular, the strategies used for (i) morphology recognition, (ii) measurement evaluation, and (iii) linguistic decision making are illustrated. The main aspect which discerns this program in comparison with other approaches to computerized electrocardiography is its ability of managing the imprecision in both the measurements and the medical knowledge through the use of fuzzy-set methodologies. So-called possibility distributions are used to represent ill-defined parameters as well as threshold limits for diagnostic criteria. In this way, smooth conclusions are derived when the evidence does not support a crisp decision. The influence of the CSE project on the evolution of the Padova program is illustrated. PMID- 2233387 TI - Methodology of ECG interpretation in the Lyon program. AB - To provide an in-depth interpretation of the spatial QRS-T contour, we established a set of vectorcardiographic parameters computed octant by octant. For each statement the criteria constitute a model which is closely related to pathophysiological patterns. The diagnostic strategy is of the heuristic type. For each diagnosis a table lists several criteria providing both specific and differential diagnostic information. Inter-table competition is handled by specific logic. The program classifies diagnoses according to the number of non satisfied criteria. Three versions are available including 124, 51 and 7 diagnoses, respectively. The first, intended for interpretation of complex situations, has given satisfactory results in such situations. Rhythm analysis is performed from 8-second recordings. All functions--acquisition, quality control, choice of a dominant complex, wave recognition, parameter extraction, interpretation, editing, storage--are integrated into a mobile cart. A complementary program performs serial analysis of successive tracings. It highlights with great precision morphological changes in the spatial loops and interval variations. PMID- 2233389 TI - Interpretation of short ECGs with a personal computer: the Porto program. AB - A computer program for ECG analysis and interpretation developed at the University of Porto, Portugal is presented. The program runs on a microcomputer and employs the three-lead Frank VCG. The signals are sampled at 250 Hz with 8 bit precision during 5.5 s. Details on signal conditioning and wave recognition and measurement techniques are given. The diagnostic part of the program uses decision-tree logic. The decision rules are mainly derived from the Washington Code. The diagnostic accuracy of four classes (normal, left and right ventricular hypertrophies and myocardial infarction), evaluated in a sample of 1,075 pediatric and adult patients and classified by ECG-independent means was 76%. The program is currently being evaluated on the CSE database. PMID- 2233390 TI - Value of scatter-graphs for the assessment of ECG computer measurement results. AB - A new method is presented, different from usual methods, for the discussion of the results of computer ECG measurement programs, based on a new graphical evaluation method. The proposed "scatter-graphs" both highlight the main program results and facilitate the comparison between various wave-recognition algorithms. They allow the distinction between the reliability of an algorithm, which is its capacity to provide a maximum of measurements with a minimum amount of errors, and its precision, i.e., the standard deviation of the differences between its point estimates and the reference. The method proves to be a powerful tool for the discussion of individual, as well as the median program results in CSE Measurement Study. It allows to highlight limitations induced in performance assessment by the variability of the reference itself, and to state that the median program is at least as close to the "Gold Standard" as the median of the referees. PMID- 2233388 TI - Methodology of ECG interpretation in the Louvain program. AB - The Louvain program performs the analysis and interpretation of the vectorcardiogram (VCG) to increase the clinical utility of ECG analysis. Among its original features, there are (1) a high-resolution vector-loop display for visual analysis, (2) quantitative analysis of the spatial VCG using age-sex stratified limits, (3) separate software for adult and pediatric series and (4) complementary deterministic and statistical methods of diagnostic classification. Using objective, ECG-independent evidence as a reference standard, the Louvain program has shown satisfactory levels of diagnostic accuracy in most basic categories. However, its usefulness is especially marked in "borderline" or "complex" situations, where the 12-lead ECG cannot provide a clear answer. It corresponds to the concept of "computer-assisted ECG interpretation" as opposed to "computer ECG analysis". PMID- 2233391 TI - Do we really value the health of the world's babies and children? PMID- 2233392 TI - Private midwives: a new approach to family planning service delivery in Ghana. AB - Data on 134 private sector midwives who were educated and trained in family planning service delivery by the Ghana Registered Midwives' Association (GRMA) showed that, for most, the course was the first they had received since qualifying as a midwife. Four out of five of the new family planning clients served by these midwives were first time contraceptive users. Approximately 9% of the clients were men, most of whom requested condoms. While delivering women is still the main function of the maternity homes, it is clear that family planning services have come to represent an important element of the health care the midwives provide. A follow-up study of family planning acceptors found extremely encouraging continuation rates. In addition, a survey of the women that the midwives had delivered showed that the contraceptive prevalence rate among these women was higher than the national rate. Providing family planning services through private sector midwives has been shown to be a very successful approach in Ghana, and one that has the potential to become a pillar of the nation's overall family planning delivery programme. As several other countries in Africa also have active private sector health networks, this approach holds promise far beyond its initial success in Ghana. PMID- 2233393 TI - Stereotypes of childbearing women: a look at some evidence. AB - We all use stereotypes to help us to behave in what we hope will be appropriate ways towards people that we have not met before. On the labour ward midwives are likely to use such stereotypes to make assumptions about what a particular woman is likely to want during labour and delivery. Two commonly encountered stereotypes are those of the 'well educated, middle-class NCT type' and the 'uneducated working class woman'. This paper explores evidence for these two stereotypes drawing on data from a large scale prospective survey of women's expectations of childbirth. The stereotypes were not supported in a number of important respects. In particular: women of different levels of education were equally likely to subscribe to the ideal of avoiding drugs during labour; the less educated women did not want to hand over all control to the staff; it was less educated women who had the highest expectations that birth would be a fulfilling experience. PMID- 2233395 TI - Nutritional requirements in pregnancy. What happens if they are not met? AB - In a previous paper (Hytten, 1990) the specific extra nutritional needs of pregnancy were described. This paper examines what happens if these needs are not met. PMID- 2233394 TI - Childbirth expectations: a qualitative analysis. AB - Maternal childbirth expectations play an important role in determining a woman's response to her childbirth experience. As part of the initial phase in the development of a research tool to investigate maternal childbirth expectations, in-depth interviews were conducted with a sample of eleven urban Canadian women in their third trimester of pregnancy. Content analysis of interview data indicated that the women had developed detailed expectations of the childbirth experience as well as for the roles of support persons and health care personnel. Exploration of women's childbirth expectations is discussed as an important component of childbirth education. PMID- 2233396 TI - Awareness among pregnant women of the effect on the fetus of commonly used drugs. AB - Epidemiological studies have shown that pregnant women continue to take substantial quantities of drugs, particularly those readily available to them without prescription. Little is known of the attitudes and knowledge among pregnant women of the effects of these substances on the fetus. Awareness of the effects on the fetus of commonly used drugs, cigarettes and alcohol among 514 women in the postnatal wards of two maternity units in Glasgow was assessed by self completion questionnaire between October 1987 and April 1988. Most of the women recognised that the fetus is most at risk of being harmed by drugs during the first 3 months of pregnancy. The majority felt it was safest not to smoke cigarettes and were aware of the adverse effects of smoking on fetal growth. Over half thought smoking was harmful while breastfeeding. Over half thought that alcohol should be avoided altogether in pregnancy and that drinking could harm the fetus. Most women considered alcohol harmful to the breast feeding baby. The majority of the women would opt for paracetamol containing analgesics only and only a small proportion would take one containing aspirin. Only half the study population would take a prescribed antibiotic. A generally high level of awareness of commonly used drugs was demonstrated although there are areas where further health education could be directed. The study has highlighted areas worthy of further research. PMID- 2233397 TI - Risk factors for birth asphyxia and brain damage in pregnancy and labour. AB - In this review the patho-physiology and risk factors of birth asphyxia are discussed. Simple and appropriate, but scientifically sound, technology for the prevention of birth asphyxia is described. This can be used at home, in the community, in health sub-centres and health centres to identify and assess risk factors so that appropriate referral can be made. Based on experience in developing countries, actions which can be performed by the mother, relatives, neighbours, traditional birth attendants and nurses and midwives are described. PMID- 2233398 TI - Surface hydrophobicity and surface free energy of Actinobacillus actinomycetemcomitans strains from human periodontitis. AB - The surface properties of five freshly isolated clinical strains of Actinobacillus actinomycetemcomitans and a non-sticky, non-cohesive colonial variant were characterized. On growth in serum-containing and serum-free media, the primary isolates had a high surface free energy, corresponding with the low hydrophobicity observed, using as assay adsorption to hexadecane. The dispersion component of the surface free energy was significantly lower upon growth in serum free medium. In the electron microscope the cells appeared covered with vesicles. In sharp contrast, the colonial variant had a very low surface free energy but still showed a low hydrophobicity in the hexadecane assay. Expression of the surface free energy characteristics in serum-grown cultures appeared strongly dependent on cell treatment, suggesting a significant influence of an adsorbed proteinaceous layer. The cells of the variant strain generally carried fewer surface vesicles. No major difference was observed in the outer membrane protein composition between parent and variant strain. PMID- 2233399 TI - Naphthoquinone pigments related to fusarubin from the fungus Fusarium solani (Mart.) Sacc. AB - A review is presented on the naphthoquinone pigments produced by the filamentous fungus Fusarium solani (Mart.) Sacc., and related species. After description of the naphthoquinone structures and biogenesis, the physiological and genetical controls of pigment production are discussed. The biological properties of the main naphthoquinone pigments so far investigated are described. Many problems still remain to be resolved in these fields, where Nectria haematococca (Berk. and Br.) Wr., the sexual state of Fusarium solani, is used as an experimental model. PMID- 2233402 TI - The race is on. A look at Michigan's gubernatorial candidates. PMID- 2233400 TI - Effect of ciprofloxacin on experimental osteomyelitis in the rabbit tibia, induced with a mixed infection of Staphylococcus epidermidis and Bacteroides thetaiotaomicron. AB - After induction of experimental polymicrobic osteomyelitis with Staphylococcus epidermidis and Bacteroides thetaiotaomicron (ciprofloxacin MIC, 0.5 micrograms/ml and 4.0 micrograms/ml, respectively), in the presence of a foreign body implant, in a rabbit tibia model, ciprofloxacin was administered to infected animals for 2- and 4-week periods. At necropsy, rabbits in the 2-weeks-treated group had mean ciprofloxacin levels of 5.94 micrograms/ml in serum, 3.63 micrograms/g in marrow, and 1.88 micrograms/g in bone. Rabbits in the 4-weeks treated group had mean ciprofloxacin levels of 7.77 micrograms/ml in serum, 5.84 micrograms/g in marrow, and 2.01 micrograms/g in bone. Quantitative bacterial plate counts were conducted on weighed samples of infected bone, marrow, and the catheter implant, taken at necropsy from treated and control rabbits. Variable reduction of bacterial numbers was observed in samples from treated animals, as compared to untreated controls. Samples of infected bone, marrow and catheter, showed comparable evidence of osteomyelitis and bacterial colonization in both treated and control animals. Although relatively high tissue levels of ciprofloxacin were attained, little therapeutic effect was observed. PMID- 2233401 TI - Growth of Mycobacterium leprae under low oxygen tension. AB - Despite numerous attempts, Mycobacterium leprae has yet to be cultivated in vitro. This organism has been considered as microaerophilic. The effects of various known gas mixtures on the in vitro growth of M. leprae were investigated. A gas mixture containing 2.5% O2 and 10% CO2 was found to be more favourable for the growth of this mycobacterium on artificial medium. Growth was evaluated by three parameters namely cell counts, bacterial ATP and DNA. An optimal growth of M. leprae, as determined by all three parameters, on both liquid and solid media was obtained between 18 and 24 weeks of incubation under optimal gas mixture. Solid medium which contained egg-yolk was relatively more beneficial for in vitro growth than the liquid medium. The cultivated bacilli exhibited some important characteristics specific for M. leprae, including growth in mouse foot-pads. The bacilli gradually lost their power of adaptation to grow on artificial media and did not show any ATP or DNA after about 36 weeks of incubation. PMID- 2233403 TI - Attorney/physician. Guidelines for inter-professional conduct. AB - It has come to our attention that many attorneys are causing record copy companies to subpoena medical records without attaching an authorization or consent signed by the patient. This is unacceptable. Physicians should never honor a third-party request or subpoena for records without a properly executed authorization signed by the patient. The power of a subpoena should never be used to put a physician in the position of violating patient confidentiality through lack of understanding or intimidation. The attorney should be responsible to see that a proper authorization is submitted with the records request or subpoena. A physician who receives a records request or subpoena without such an authorization should immediately communicate refusal to comply and the reason to the initiating attorney. The medical and legal professions have established an attorney/physician code covering this and related issues. The code is set forth verbatim. PMID- 2233404 TI - Michigan Health Care Data Corporation. The first and only statewide voluntary health data system in the US. AB - To continue its mission of providing information to improve understanding of health care in Michigan and to aid in planning and decisionmaking, the Michigan Health Care Data Corporation needs to achieve several things. The following is a look at its history and structure, MSMS participation, public reports, and future expectations. PMID- 2233405 TI - Disposition of a medical practice. PMID- 2233406 TI - Graduate medical education and state law. PMID- 2233407 TI - A creative partnership between practicing physicians and local health departments could help everyone. PMID- 2233408 TI - Midwifery education in Japan. PMID- 2233409 TI - Why education? PMID- 2233410 TI - Breast-feeding practices in Japan. PMID- 2233411 TI - Japan's Maternal and Child Health Handbook. PMID- 2233412 TI - [Changes in the energy indices of Escherichia coli during exhaustion and renewal of glucose and ammonia supply as a factor responsible for the coupling of energy and constructive types of metabolism]. AB - The shift down of glucose in the growth medium lowered the energetic status of cells whereas that of ammonium elevated it, which was indicative of their specific effect on metabolism. The shift up of glucose within the first four seconds promptly increased the intracellular ATP pool, the energy charge and the ATP/ADP ratio up to values characteristic of growth, while the addition of ammonium after its exhaustion resulted in the opposite effect. The described changes are typical of an incomplete coupling between energetic and constructive metabolic types in E. coli. PMID- 2233413 TI - No correlation between tumor markers and prognosis under polygenic control systems. AB - Tumor markers in serum should not be correlated with the prognosis of patients with malignant tumors, although the markers indicate the presence of tumors, since marker levels and prognosis are controlled independently by poly-genes. Furthermore, prognostic factors, including incidence of pulmonary metastasis, tumor growth rate, tumor drug sensitivity and host response, vary among patients. In general, tumor markers may be used to demonstrate response of tumor to treatments only when expression of the markers does not change in a time dependent manner. PMID- 2233414 TI - Pickles, peptide hormones and pregnancy: a hypothesis. AB - In western societies a high frequency of heartburn, nausea and vomiting occur during pregnancy. The causes and mechanisms of these clinical symptoms remain poorly understood. Evidence suggests steroid hormones modulate gastrointestinal transit time and plasma peptide hormones, while peptide hormone modulated food intake and preferences. Since diurnal and episodic release of steroid and peptide hormones occur, it is postulated that heartburn and other digestive dysfunction during pregnancy are associated with elevated steroid and peptide (beta endorphin, NPY) hormone interaction with innate biological rhythms controlling the gastrointestinal tract. PMID- 2233415 TI - Alcohol withdrawal syndrome--an auto-immune disease? A neuroimmunologic model for pathogenesis of alcohol withdrawal symptoms. AB - A neuroimmunologic model of alcohol withdrawal symptoms is developed according to which these may be considered as an idiopathic auto-immune disease. During the alcohol abuse period of non-addicts, homeostasis may alter pathologically by gradual adaptation of the organism: auto-sensitisation develops and finally leads to the breakdown of auto-immune tolerance of the structural modifications set by alcohol withdrawal. The immunosystem regards the existing assimilation of alcohol as self, the withdrawal of alcohol as non-self. Alcohol withdrawal may be considered as an acknowledged physical stressor, and physical stressors as potential triggers of auto-immune diseases. Some so-called alcohol-induced diseases may originate in the pathogenic effects of preceding auto-immune responses to repeated alcohol withdrawals. Neuroimmunologic preconditions of potential auto-immune diseases exactly fit the alcohol withdrawal situation. Neuroimmunologic diseases themselves show close analogies respectively to alcohol withdrawal symptoms as well as to some alcohol-induced diseases. The myelin basis protein is assumed to be a potential auto-allergen. Finally withdrawal symptoms being the expression of physical dependence on alcohol, the model may highlight the very nature of physical dependence. PMID- 2233416 TI - The 'hyperprosexia phenomenon' in traumatic brain injured patients (a forgotten term for an old problem). AB - In traumatic brain injured patients the basic functions of the cognitive, behavioral, emotional and intellectual systems are disturbed. The patients' ability to regulate the interaction between the ego and the external world is diminished and they present inflexible, concrete and sometimes inappropriate behavior. We have not observed anosognostic phenomena in these patients. Most of them are preoccupied with their physical impairments and unaware of their intellectual deficits. We hypothesize that this preoccupation or 'hyperprosexia phenomenon' may be observed in traumatic brain injured patients. The various neuropsychological, medical and philological aspects of these terms are discussed. PMID- 2233417 TI - Potential role of acute hypophosphatemia during hypokalemic periodic paralysis attack. AB - A paralysis attack was induced by glucose load in a patient with hypokalemic periodic paralysis. A profound drop in serum phosphorus was observed (from 3.0 to 0.8 mg/dl) in parallel to the serum potassium decrease. The potential role of phosphorus metabolism in the pathophysiology of muscle weakness in this disease is discussed. PMID- 2233418 TI - Parkinson's disease and cytochrome P450: a possible link? AB - The possibility that idiopathic Parkinson's disease may be linked to a deficiency of an important detoxifying enzyme such as the cytochrome P450 enzyme bufuralol hydroxylase is examined. A hypothetical model of how this might operate to produce early onset Parkinson's disease is suggested. PMID- 2233419 TI - Competing antagonists to energy production in space and their effect on calcium metabolism. AB - In microgravity, energy demand and its production are impressively decreased resulting in the clinical consequences of negative calcium balance and inhibited biosynthesis. Increased concentration of the underutilized ATP inhibits phosphorylation and decarboxylation resulting in increased tricarboxylates. Citrates mobilize calcium resulting in diseases mediated by the withdrawal of the citrate complexed calcium from hard and soft tissues. If man is to live in space for extended periods of time, he must dramatically reduce antagonists to energy production and substitute measures that enhance metabolic respiration. PMID- 2233420 TI - Space adaptation syndrome is caused by elevated intracranial pressure. AB - Space adaptation syndrome (SAS) incapacitates about 50% of the astronauts with symptoms of headache, malaise, vomiting, vertigo, etc. A hypothesis that SAS is caused by elevated intracranial pressure secondary to the cephalad fluid shift in zero G is proposed. A mechanism of how the cephalad fluid shift could cause elevated intracranial pressure is discussed. Factors known to alleviate and exacerbate SAS are interpreted in light of the elevated intracranial pressure mechanism. PMID- 2233421 TI - Stress-adaptation failure hypothesis of Alzheimer's disease. AB - It is proposed that the higher incidence of chronic stress-adaptation failure in patients with Alzheimer's disease is of specific etiopathological significance. Such chronic stress-adaptation failure leads to a vicious circular reaction, namely: intense, stressful stimuli----neocortico-limbic excitation----hypothalamo pituitary-adrenocortical (HPA) axis activation----excessive secretion of neurohormones including cortisol----stimulation of inhibitory glucocorticoid sensitive hippocampal neurons----failure to terminate the HPA axis response--- chronic excessive secretion of neurohormones including cortisol--- overstimulation degeneration of glucocorticoid sensitive hippocampal inhibitory neurons----progressive cognitive-affective behavioral disorganizational failure which is typical of dementia of the Alzheimer's type. Possibilities of neuropharmacological corrections and neurobehavioral re-education are suggested. PMID- 2233422 TI - The integration of the cerebral and coronary circulations with the dynamic system structure of brain and myocardium and the form of the cerebral and coronary artery trees. AB - Cerebral and coronary arterial trees lack functional anastomoses and are 'non redundant' in the number of arteries. These two morphological characteristics expose brain and myocardium to vascular pathologies. An elementary model common to the cerebral and myocardial blood supply permits an explanation of the two characteristics. On the ground of this model the brain and the myocardium are represented as dynamic systems--organ-systems--made up of units, these corresponding to neurons and to cardiac cells. A flow of information between the units determines variations of state of the units. The whole of the variations of state of the units gives the organ-system function. The artery tree is considered as an information channel--tree-channel--that conveys information to the units. This artery-transmitted information determines the way the units function. The tree-channel always emits the same message. Therefore the artery-transmitted information does not cause local or temporal variations in the functioning of the units. On the contrary, if the tree-channel is noised the ending branches will emit randomly varied messages. Such random emission--disorder--will cause random loco-temporal variations in the functioning of the units. Consequently the functioning of the organ-system will be disturbed. It is shown that a low number of branches lowers the quantity of disorder that a noised tree-channel can emit. The absence of anastomoses avoids combinatory phenomena between the diverse messages that would increase the disorder. Biological and pathological evidence supports the model and the explanation. PMID- 2233423 TI - Popperian everyday diagnostics--the growth of diagnostic knowledge in the particular case. AB - In an earlier paper the Bayesian model for everyday diagnostics of disease in the particular patient and the Bayesian decision model was criticized. Here a Popperian model is applied and its presumptions and consequences are investigated. Abandoning calculable probabilities as Popper suggests in science, and substituting them with degrees of corroboration, is realistic. PMID- 2233424 TI - Bovine spongiform encephalopathy--a new disease transmissable to humans? AB - Current concerns about the cattle disease bovine spongiform encephalopathy do not appear to take cognisance of the parallel with scrapie, the similar/identical disease of sheep/goats. This has existed for 200 years, and clearly involved a longstanding consumption of meat/offal from affected animals, but apparently without consequential human disease. A summary is given of the characteristics of the human and animal spongiform encephalopathy diseases and their causative agents. The conclusion of the official Southwood Report that the bovine disease is caused by the inclusion of sheep scrapie material in cattle fodder is critically discussed: an alternative mechanism is proposed for its emergence. PMID- 2233425 TI - Transcutaneal suture ligations of varicose veins. PMID- 2233426 TI - Male sex and heart disease--iron loss in semen? PMID- 2233427 TI - Bone marrow transplantation. PMID- 2233428 TI - An NHMRC code for the conduct of science. PMID- 2233429 TI - Chemonucleolysis: a further look at a contentious issue. PMID- 2233430 TI - The perinatal autopsy. PMID- 2233432 TI - Leg ulcers in rheumatoid arthritis. AB - A retrospective study over an eight-year period of 33 episodes of leg ulceration in 26 patients with rheumatoid arthritis requiring inpatient management is reported. the aetiology of the ulcers was found to be multifactorial. The most common factors were venous insufficiency (45.5%), trauma or pressure (45.5%) and arterial insufficiency (36.4%). Vasculitis (18.2%) and Felty's syndrome (12.1%) were less frequent causes, and pyoderma gangrenosum was rare. Most patients had seropositive erosive disease with high rheumatoid factor titres and significant functional impairment; over half were on maintenance corticosteroids. Colonisation of the ulcers by organisms, predominantly Staphylococcus aureus, was common (69.7%). Skin grafting was required in 63.3%, but the rate of complete take was only 42.9% despite multiple attempts. Hospitalisation was prolonged (mean 47.9 days) and the recurrence rate requiring further hospitalisation was 26.9%. The diagnosis of vasculitis and the limited role of biopsy in establishing its presence are discussed. PMID- 2233431 TI - Bone marrow transplantation: a review of a programme and its first 100 patients. AB - We review the first 100 patients receiving a bone marrow transplant as definitive therapy for their underlying disease. These patients were treated between May 1975 and June 1988. Median age was 8 years (range, 1 month to 43 years). Initially, patients were given transplants late in their disease but, as the programme progressed, patients were given transplants earlier and while in remission from their disease. The types of disease considered for treatment by bone marrow transplantation (BMT) expanded from leukaemia, and aplastic anaemia to include neuroblastoma, thalassaemia and immune deficiency. Initially matched donors were used but the source of marrow broadened to include mismatched family members, matched unrelated donors and autologous marrow. Problems after BMT were rejection (11%), acute graft-versus-host disease (GVHD) (45%), interstitial pneumonitis (22%) and relapse (36%). Recurrence of disease was the cause of half the deaths. GVHD was less frequent with the use of methotrexate and cyclosporin, T-cell depleted marrow or matched donors. Interstitial pneumonitis was more commonly associated with the use of mismatched donors and the development of GHVD. Relapse was less likely when BMT was undertaken in the first remission. At least one long-term side effect was seen in all patients treated with total body irradiation whereas no patient treated without irradiation had long-term side effects. The rate of disease free survival of patients at 24 months was 56% for matched, 48% for closely matched, 46% for autologous and 29% for mismatched transplants. For matched transplants mortality within the first 6 months after transplantation decreased from 28% before 1984 to 5% since 1984. Fifty-one patients have survived to June 1989, 49 of them disease free, for periods ranging from 12 to 123 months (median 29 months). PMID- 2233433 TI - Hypertension control and the risk of myocardial infarction and stroke: a population-based study. AB - A population-based case-control study was performed to determine the importance of the presence of hypertension and the control of blood pressure level during treatment for hypertension on the occurrence of acute myocardial infarction (AMI) and stroke in persons aged 35-69 years in the Hunter Region community. Patients with a first episode of AMI or stroke were identified from community-based heart attack and stroke registers and compared with control subjects obtained from a random population sample from the same community. Twenty per cent of control subjects were currently receiving treatment for hypertension compared with 37% of patients with myocardial infarction (odds ratio adjusted for age, sex and several other possible confounding variables, 2.6; 95% confidence interval (CI), 1.9-3.4) and 51% of patients with stroke (adjusted odds ratio, 3.5; 95% CI, 2.3-54). Among those who had ever been told they had hypertension, 71%, 73% and 59% of patients with AMI, patients with stroke and control subjects, respectively, were receiving treatment at the time of the AMI or the stroke or at the time of the survey (control subjects). For those receiving treatment for hypertension, blood pressure levels were obtained from the records of their general practitioner. Despite similar pretreatment levels the last recorded blood pressure level (either before the survey of the development of AMI or stroke) was higher among those who developed AMI or stroke than those in the control group. Those with a treated diastolic blood pressure of less than 80 mmHg appeared to be at a higher risk of both AMI and stroke than those with a treated diastolic blood pressure level of 80-89 mmHg, but the difference was not statistically significant. Randomised controlled trials do not show a reduction in rates of AMI in response to a reduction of blood pressure. Nevertheless our findings suggest that the presence of hypertension and poor control of blood pressure levels despite treatment may be important aetiologically both for AMI and stroke occurrence. PMID- 2233434 TI - Psychotropic drugs in Australia: consumption patterns. AB - This paper reviews studies of psychotropic drug use in Australia, analyses results from the Australian Health Surveys and compares the findings with those from other countries. It identifies subpopulations with high rates of drug use, which may consequently be at greater risk of drug-related harm. The levels of consumption of psychotropic agents in Australia were estimated from the results of studies conducted in community and institutional settings between 1970 and 1986. In the absence of more recent data national prevalence rates were derived from analysis of data provided by the Australian Health Surveys (AHS) of 1977 1978 and 1983-1984, and comparisons were made with rates available from other countries. While the prevalence of current and frequent use of drugs for nervous conditions was found to have decreased in most age groups over this period, it was consistently higher in females than in males, and increased with age. An analysis of the 1983-1984 AHS data revealed that the consumption of "medicines for nervous conditions" fell by 35% but that no change occurred in the prevalence of persons taking sleeping medicines. This fall appeared to occur in both rural and urban populations. Further analysis of data relating to the consumption of hypnotic agents revealed that changes occurred in the patterns of use within age and gender subgroups. Significant differences were observed between Australian States in consumption rates of sleeping medicines (chi 2 = 282.2; df = 7; P less than 0.01) and of medicines for nervous conditions (chi 2 = 289.7; df = 7; P less than 0.01). There were high rates of use of medicines for sleep in South Australia and of medicines for nervous conditions in Queensland. The prevalence of use of both drugs for sleep (rs = 0.71; P less than 0.05) and drugs for nervous conditions (rs = 0.77; P less than 0.05) was related to the rate of consultations with doctors. Preliminary surveys of various non-British subpopulations including Aborigines were inconclusive. These results have implications for reducing the harm associated with the use of psychotropic agents, particularly hypnotics and drugs for nervous conditions, in Australia. PMID- 2233435 TI - The pivot: the First Australian Casualty Clearing Hospital at the Gallipoli beachhead--the first seven days. AB - In October 1914, a new type of medical unit was added to the order of battle of the Australian Army's casualty evacuation chain. Designated the casualty clearing hospital, it was called a Casualty Clearing Station on the beach at Anzac Cove in the Gallipoli campaign. This unit was established as the most forward unit to provide emergency surgery, freeing the forward field ambulances from the necessity of holding wounded soldiers, a task which compromised their mobility and prevented them from moving with the brigades they supported. The Casualty Clearing Station was to be the most forward unit where specialist surgeons, anaesthetists, nurses, radiologists and a dentist were to be found. The 1st Australian Casualty Clearing Station (1ACCS) was raised in Hobart and consisted of 93 men including 7 doctors. After some seven weeks of training in camp, the new unit embarked for Egypt and the Gallipoli offensive. They landed on the beach at Anzac Cove at 11 a.m. on 25th April 1915, and remained on a 20 metre stretch of beach through eight months of the Gallipoli campaign. This paper reviews the first seven days of the Station's role at Anzac Cove, during which time this essentially inexperienced medical unit treated and evacuated an estimated 2700 wounded Australian and New Zealand soldiers. This paper also reviews the Commanding Officer's hitherto unpublished war diary and other archival and family records which add to the medical story of Anzac. This frightful baptism of mass casualty evacuation, undergone by the Australian Army Medical Corps, brings a perspective to the problems of mass disasters today. PMID- 2233436 TI - The final assault--Gallipoli 1990. PMID- 2233437 TI - Stress and hypertension--a critical review. AB - Recurrent psychosomatic stress has been popularly thought to cause permanent hypertension by repeated reactive blood pressure elevations. These are considered by some to be caused by various mechanisms, including an increased sympathetic outflow and a decreased parasympathetic inhibition, or possibly an inborn functional abnormality in the walls of the resistance vessels, which becomes a structural abnormality as a result of the elevated pressure. Recent work, however, has questioned some of these concepts. Many of the assumptions in the past concerning the ill-effects of elevated blood pressure have been based on clinic or office readings. With the more widespread use of ambulatory monitoring, first developed in the 1960s, information has accumulated which has helped to clarify the predictive value of such office readings. Ambulatory monitoring has also given much information about the relationship between daily activities, blood pressure reactivity and the mean daily blood pressure level. It appears that only the mean daily level is related to cardiovascular morbidity and mortality. Variations in blood pressure in response to bodily and mental activity are not so related. Nor has it been shown that variability is a precursor of fixed hypertension. The role of laboratory stressors is discussed to see whether they are predictive of future hypertension and whether they reflect real life situations. Clinical studies of the relationship between stress and hypertension and, in particular, specific causes of stress such as anxiety and hostility are considered. It is concluded that there is no satisfactory evidence that psychosocial stress leads to the elevation of the mean daily blood pressure with its pathogenic connotations. PMID- 2233438 TI - Sarcomatous mesothelioma of the pleura with cerebral metastases. AB - A case of sarcomatous pleural mesothelioma in a 22-year-old woman is presented. There was no history of occupational exposure to asbestos. Twenty months after the first symptoms occurred the patient noticed weakness in the right arm. A computed tomography scan of the brain showed multiple metastases. The patient died 10 days later. PMID- 2233439 TI - Use of tranexamic acid mouthwash in dental procedures in patients taking oral anticoagulants. PMID- 2233441 TI - Pap smear rates in New South Wales--1984 to 1988. PMID- 2233440 TI - Evening primrose oil and premenstrual syndrome. PMID- 2233442 TI - Side effects of rubella immunisation in teenage girls. PMID- 2233443 TI - Eritrean medicine. PMID- 2233444 TI - Lymphoedema: a vascular problem. PMID- 2233445 TI - Osteomyelitis: approaching the 1990s. PMID- 2233446 TI - Training aboriginal doctors. PMID- 2233447 TI - Screening: the need for a population register. PMID- 2233448 TI - Diabetes among aboriginal people in central Australia: a high prevalence based on health service attendance. AB - The prevalence of diagnosed diabetes in Aboriginal people living in central Australia (population, 9983) was determined by collating data from the hospital, rural and urban health services, nursing homes and death registers. A total of 98 male and 183 female Aboriginal residents with diabetes attended health services in central Australia between January 1984 and December 1986. The point prevalence of diagnosed diabetes at the end of 1986 in the age group 25-34 years was 1.6% in men and 3.1% in women, and in those over 35 years, 8.8% and 14.1%, respectively. The true prevalence of diabetes (diagnosed and undetected) is likely to be at least twice this rate, and constitutes a major public health problem in central Australia. Diabetes and other disorders such as obesity, hypertension and ischaemic heart disease have common antecedents and outcomes. The control of these non-communicable diseases requires integrated and culturally appropriate educational, social and medical strategies. PMID- 2233450 TI - A prospective study to assess the efficacy of ketoconazole in the treatment of recurrent vaginal candidiasis. AB - A prospective study of oral ketoconazole therapy was undertaken in 40 women who suffered from recurrent thrush. Symptoms were relieved within three days for half the women, and two-thirds of the women maintained an absence of symptoms for a period of at least a month. Over 80% of the patients assessed the treatment as being effective, with 90% preferring oral to topical therapy. PMID- 2233449 TI - Trends in caesarean section in Western Australia, 1980-1987. AB - During the 1980s the incidence of both emergency and elective caesarean section in Western Australia increased, accompanied by a decrease in that of all other delivery methods. The proportion of emergency caesarean sections increased from 5.9%. of all deliveries in 1980 to 8.2% in 1987 and that of elective sections from 5.3% to 8.7%. For each year studied less than 50% of primiparous women delivering singletons had a normal vaginal delivery. Emergency caesarean sections were more common in primiparas and at the teaching hospital and elective sections in multiparas and at the metropolitan private hospitals. The proportion of primiparas having either emergency or elective caesarean sections rose with maternal age, but for multiparas the proportion having elective sections rose, but there were few differences in emergency sections with increasing age. Repeat caesarean sections, which made up 28.8% of the total in 1987, have contributed increasingly to the rising proportion of caesarean section deliveries. Unless the number of emergency sections in primiparous women falls and the challenge of vaginal birth after caesarean section is met, it is likely that the caesarean section rate in Western Australia will continue to increase over the next decade. PMID- 2233451 TI - Invasive disease due to Salmonella virchow: a north Queensland problem. AB - Salmonella virchow is the second most commonly isolated salmonella serotype from human sources in Australia, and overseas studies indicate that S. virchow is a significant cause of extraintestinal salmonellosis. The successful management of three infants, two with septicaemia and one with leptomeningitis and septicaemia due to S. virchow, is described. A review of the Townsville General Hospital laboratory records (1978-1988) showed that, among other aspects, S. virchow accounted for 46% of all salmonella septicaemias, further exemplifying the invasive propensity of this serotype. Information obtained from various sources, after crude analyses, demonstrates that more than 90% of S. virchow infections in humans in Australia occur in Queensland, and that most (greater than 78% in 1987) of those infections in Queensland come from a coastal zone north of Bundaberg, with the highest concentration (0.4 per 1000 persons) occurring in the Cairns region. PMID- 2233452 TI - Acute rheumatic fever and rheumatic heart disease in a rural central Australian aboriginal community. AB - A retrospective study of clinical case records was conducted at the health centre of a rural central Australian Aboriginal community to determine the frequency of acute rheumatic fever and of rheumatic heart disease between 1978 and 1987. The case records of 976 residents over 5 years of age were examined for evidence of the clinical indicators of acute rheumatic fever or rheumatic heart disease; together they contributed 8015 person-years of study. During the 10-year study period, 18 patients developed acute rheumatic fever and 12 patients had rheumatic heart disease. The annual incidence of acute rheumatic fever (first and recurrent attacks) for children aged 5-14 years was 815 per 100,000 person-years. For the residents aged 5 years and over, the point prevalence for rheumatic heart disease at the end of 1987 was between 7.9 and 12.3 per 1000 persons, according to health clinic records and the official population census, respectively. These rates are similar to those reported for Third World countries. Preventive measures must include efforts by health professionals to help to alleviate the adverse living conditions in Aboriginal communities. PMID- 2233453 TI - Obstetrics and litigation: a consumer perspective. PMID- 2233454 TI - Abnormal illness behaviours and their treatments. PMID- 2233455 TI - A unique mental health network for Victorian aboriginal people. AB - The Victorian Aboriginal Mental Health Network (VAMHN) is a unique mental health programme for Aboriginal people in Australia. The network was set up in 1987. The services and programmes developed include a community consultation service, a psychiatric inpatient unit; and educational, evaluative and research programmes. Utilisation of the network has steadily increased and the demand for both primary and secondary consultations continues to grow. PMID- 2233456 TI - Aerosol delivery in lung disease. AB - Metered-dose inhalers are the preferred method of aerosol delivery under normal circumstances because of their convenient size, ease of use and better patient compliance. Where poor coordination exists a spacer device, breath-activated inhaler or powder inhalation should be used and if muscular weakness presents a problem a Haleraid should be tried. A clinical air pump with jet nebuliser is appropriate if these methods prove unsatisfactory; where wet aerosol has been shown to result in clearly superior effects; for very small children; and for the "brittle" asthmatic prone to sudden life-threatening attacks, especially patients living in isolated conditions. Regular checks on aerosol techniques and efficacy of therapy are important aspects of follow up and education of all patients with airflow obstruction. PMID- 2233457 TI - "Stockpiling" psychotropic drugs and HIV infection. PMID- 2233458 TI - Notification of HIV infection. PMID- 2233459 TI - Tropical arthritis in Papua New Guinea: a reactive arthritis. PMID- 2233461 TI - The self-seeking syringe. PMID- 2233460 TI - The diagnosis of breast cancer. PMID- 2233463 TI - Drug company representative. PMID- 2233462 TI - HDL-cholesterol testing. PMID- 2233464 TI - The health effects of chemical waste in an urban community. PMID- 2233465 TI - Trends in asthma mortality in Australia, 1911-1986. PMID- 2233466 TI - Dangers of immunotherapy for the treatment of asthma in children. PMID- 2233467 TI - Which waist-hip ratio? PMID- 2233468 TI - Are blackflies in Australia? PMID- 2233469 TI - Methylprednisolone in the management of acute spinal cord injuries. PMID- 2233470 TI - Liver transplantation in children. PMID- 2233471 TI - Patterns of treated non-melanoma skin cancer in Queensland--the region with the highest incidence rates in the world. AB - The incidence of non-melanoma skin cancer, comprising basal cell carcinoma and squamous cell carcinoma, was studied in Queensland during 1984. The world standardised annual incidence rates (per 100,000 population) for the number of persons with non-melanoma skin cancer were estimated to be 1372 for men and 702 for women, the highest recorded incidence rates in the world. Rates in men were nearly double the rates in women and age-specific incidence rates increased curvilinearly with age. There were, on average, 1.4 skin cancers per person with non-melanoma skin cancer and the ratio of basal cell carcinomas to squamous cell carcinomas was approximately three to one. The age-standardised annual incidence rate (per 100,000 population) of basal cell carcinoma for residents of the Gold Coast was 1.83 times the Brisbane rate for men and 1.57 times that for women, indicating significant differences between the two regions. For squamous cell carcinoma the regional differences were not statistically significant. The average potential number of non-melanoma skin cancers (per person) treated during the lifetime of a cohort of 100,000 was estimated to be 0.014 for men and 0.009 for women by age 40. By age 65, these numbers increased to 0.22 for men and 0.11 for women. At age 90, these average numbers were 1.09 and 0.42, respectively. Although the incidence of non-melanoma skin cancer is much higher in the older age groups, it should be kept in mind that it also affects the younger population; 1028 Queenslanders under 40 required treatment for 2300 non-melanoma skin cancers in 1984. This study which provides baseline information about the occurrence of non-melanoma skin cancer in Queensland emphasises the importance of developing safe sun-exposure habits, detecting non-melanoma skin cancer early and protecting and restoring the atmosphere. PMID- 2233472 TI - Cost comparison of intravenous antibiotic administration. AB - The cost of preparing and administering intravenous antibiotics in an Australian teaching hospital was determined. The costs associated with acquisition, delivery (administration system, ancillary equipment, labour), and laboratory monitoring for potential toxicity were calculated. Standard regimens based on antibiotic guidelines were used to compile the daily total cost. The results indicate that these components affect the daily total cost of individual antibiotics in different ways. Acquisition cost is often a poor predictor of total cost, which ranges from 1.2 times to almost eight times the acquisition cost. Less frequent administration reduces total costs substantially, as does slow injection compared with infusion. Laboratory costs constitute between 3.6% and 23% of the daily total cost and are most pronounced with antibiotics that have low acquisition costs. Antibiotic cost containment should not focus on acquisition cost alone. Daily total cost to administer antibiotics is a more appropriate and accurate costing method. Hospitals must acknowledge the need for innovative resource allocation methods which recognise this fact. PMID- 2233473 TI - Suicide and related deaths in Victorian doctors. AB - A cohort of University of Melbourne medical graduates (1950-1959 graduates inclusive) was followed up until December 31, 1986. Vital status at the end of the study period was ascertained and, for those who had died, cause of death was determined. The cohort consisted of 1453 members (1279 men and 174 women). One hundred and twenty-six of the group had died (115 men and 11 women) and 68 (4.7%; 57 men and 11 women) were lost to follow-up. The major causes of death were cardiovascular disease and malignant neoplasms. The standardised mortality ratios (SMRs) for all-cause mortality were low (59 for the male doctors and 84 for the female doctors) indicating that male doctors experience a "force of mortality" 59% that of the general population and female doctors 84%. For the male doctors, the SMR for suicide was 113 (95% confidence interval [CI], 54-207) (10 of 115 deaths in male doctors) about double the SMR for mortality from all causes. For the female doctors, the SMR for suicide was 501 (95% CI, 103-1500) (3 of 11 deaths in female doctors). For deaths resulting from all accidents the SMR was low for the males (29) and higher for the females (126). The SMR for mental disorders for the male doctors was marginally raised (132). This study reveals some indication of a problem in doctors in regard to deaths by suicide, other violent deaths and mental disorders. A larger study involving a control group of equivalent social class is required to confirm the findings of this study. PMID- 2233474 TI - Prevalence of chronic fatigue syndrome in an Australian population. AB - An epidemiological study was undertaken to provide the first reported estimate of the point prevalence of chronic fatigue syndrome in an Australian community. After a pilot study in a separate location, the population of the Richmond Valley, New South Wales, was sampled using a structured case-finding technique, which included notification from local medical practitioners, the use of a screening questionnaire and standardised interviews conducted by a physician and psychiatrist. In addition, investigations were performed to exclude alternative diagnoses and to assess cell-mediated immunity. Forty-two patients with chronic fatigue syndrome, with a female:male ratio of 1.3:1.0, were detected in a population of 114,000. The mean age at onset of symptoms was 28.6 years (SD, 12.3 years), and the median duration of symptoms from onset to sampling date was 30 months. The social status of the patients was distributed in accordance with that of the remainder of the population sampled, with no bias towards the middle or upper social classes. The disorder was causing considerable incapacity, with 43% of patients unable to attend school or work. The conservative estimate from this study suggests a prevalence on June 30 1988 of 37.1 cases per 100,000 (95% confidence interval [CI], 26.8-50.2). Chronic fatigue syndrome is an important disorder in this Australian community that affects young individuals from all social classes and causes considerable ill health and disability. PMID- 2233475 TI - Muscle versus brain: chronic fatigue syndrome. PMID- 2233476 TI - Pharmacokinetics in acute illness. AB - Severe illness at any age is accompanied by organ dysfunction, the administration of numerous drugs and complex changes in drug absorption, disposition and action. The clinician faced with a seriously ill patient should be aware of the important principles of drug treatment in critical illness. With acute illness of all types, the premature infant and the octogenarian lie at opposite ends of an age spectrum which encompasses the gamut of human disease and changeable organ pathophysiology. The common requirement of this host of variables is a flexible management plan, and careful observation of the patient's response to a therapeutic regimen which has been based on a sound knowledge of drug pharmacokinetics. PMID- 2233477 TI - The accreditation of undergraduate medical education in Australia. AB - The Australian Medical Council was established in 1985 with one of its three functions being the accreditation of medical schools and of courses leading to basic medical qualifications. The Accreditation (Standing) Committee has developed guidelines for assessment and accreditation in Australia, and commenced its programme of visits to Australian medical faculties in March 1988, with the tenth faculty scheduled to be visited in September 1993. This article describes the process of assessment and accreditation developed in Australia by the Australian Medical Council. A later article will discuss the issues in medical education that have been identified during the process of accreditation. PMID- 2233478 TI - A training programme for rural general practice. AB - An improvement in methods of training graduates for general practice has been recommended as a result of several investigations into the problems faced by rural medical practitioners. This paper describes a rural vocational training programme conducted by the Family Medicine Programme in North Queensland. The programme combines educational support, professional support and mentorship with a medical educator experienced in rural practice. The educational support is partly chosen by members of the rural group, and is designed to meet needs of group members and the communities they serve. The cost of such a programme is high, due to travel and communication over long distances, but is justifiable if it improves recruitment and retention of rural practitioners. PMID- 2233479 TI - Communication and health--health as an ecosystem. AB - The importance of communication in public health is described with reference to recent experiences in Australia where good progress has been made with certain major public health problems. There has been a 30% fall in road accident deaths and a 40% fall in deaths from coronary heart disease, and a smoke free environment has been established in public places and in the work place. These successes depended on effective communication based on appropriate data. Evaluation data have also been used to keep the public informed and to reinforce the message. The cooperation of the media has been most important in stimulating a new awareness of health and the opportunities for self help and community initiatives. In central Australia, new initiatives involving the Central Australian Aboriginal Congress have led to an improvement in the health of Aborigines, the training of Aborigines as health workers and the development of a Centre for Appropriate Technology at the Alice Springs College of Technical and Further Education. At the international level, Australia sponsored a World Health Assembly resolution in 1986 calling for the elimination of iodine deficiency disorders. With the support of the Australian International Development Assistance Bureau and the United Nations Children's Fund (UNICEF), an international expert group of scientists and public health professionals, the International Council for Control of Iodine Deficiency Disorders (ICCIDD), based in Adelaide, has been able to work with the World Health Organization (WHO) and UNICEF in the development of an international public health programme aimed at eliminating iodine deficiency disorders by the year 2000. The ICCIDD is a new model for communication and action in international health which is now being advocated for other areas. PMID- 2233480 TI - The prediction of suicide. AB - The prediction of suicide remains a major challenge for health professionals. Sociodemographic predictors of the risk of suicide lack specificity: factors such as living alone, being unemployed, or having a physical or mental illness are common, separately or in combination, but suicide is rare. Psychiatric conditions, such as depression, alcohol dependence, schizophrenia and personality disorders, are strongly associated with suicide, but most psychiatrically ill patients do not suicide. Most suicidal patients consult a helping agency within a month of their act and, in practice, successful assessment of the risk of suicide and intervention to prevent it depend on gaining an understanding of the individual patient and developing a therapeutic relationship. More research into the biological, psychological and social factors that distinguish suicidal from non-suicidal individuals is needed. We review key studies that have addressed the issue of suicide prediction, outline the clinician's role in evaluating the risk of suicide in the individual, and suggest directions for future research. PMID- 2233481 TI - Diaphragmatic paralysis following cervical herpes zoster. AB - A 74-year-old man was found to have a paralysed left hemidiaphragm within four months of the appearance of a typical herpes zoster rash involving his left shoulder and neck. Investigations, including bronchoscopy and computed tomography of the chest, failed to detect a cause for the diaphragmatic paralysis. We believe that the cervical zoster and diaphragmatic paralysis were causally related, a rare but recognised association. PMID- 2233482 TI - An unusual presentation of herpes zoster. PMID- 2233483 TI - Muscle side effects associated with simvastatin therapy. PMID- 2233484 TI - Guns and violence in Australia. PMID- 2233485 TI - Hand dermatitis caused by Peruvian lily. PMID- 2233486 TI - Alzheimer's disease and omega-3 fatty acids: hypothesis. PMID- 2233487 TI - Colorectal cancer. PMID- 2233488 TI - Risk of HTLV-1 transmission in renal transplantation among aborigines. PMID- 2233489 TI - Severe heat stroke in an experienced athlete. PMID- 2233490 TI - Cricopharyngeal myotomy. PMID- 2233491 TI - Variation in cholesterol levels. PMID- 2233492 TI - Hyper IgE syndrome? A new disease. PMID- 2233493 TI - Endometriosis and social class. PMID- 2233494 TI - Thiamine in our bread and wine. PMID- 2233495 TI - Introduction or artificial limbs scheme. PMID- 2233496 TI - True and false contraindications to pertussis vaccine. PMID- 2233497 TI - Skateboard injuries. PMID- 2233499 TI - Confidentiality ad absurdum. PMID- 2233498 TI - Foreign medical graduates. PMID- 2233500 TI - Snake venom allergy. PMID- 2233501 TI - Marbled beef. PMID- 2233502 TI - Residential care for Australians with dementia. PMID- 2233503 TI - Seatbelts save lives. PMID- 2233504 TI - Nuts and iron deficiency. PMID- 2233505 TI - [Iodide instead of L-thyroxine]. PMID- 2233506 TI - [Postural problems at the work site. Prevention of pain and physical damage by proper sitting, standing, gait and lifting]. PMID- 2233508 TI - Desk-top systems for office chemistries. PMID- 2233507 TI - [Drug information. Instructions for storage and administration. Drugs for use in the nose and ear]. PMID- 2233509 TI - Botulinum toxin for ocular muscle disorders. PMID- 2233510 TI - Moricizine for cardiac arrhythmias. PMID- 2233511 TI - Prevention and treatment of nerve gas poisoning. PMID- 2233512 TI - Olsalazine for ulcerative colitis. PMID- 2233513 TI - Impact of political change on the psychological stress process among West Bank Palestinian women. AB - This article reports the relationships between political change, personal factors and the psychological stress process among 40 West Bank Palestinian women. The women were tested in spring 1982 and in autumn 1985. The stress process assessed consists of exposure to stressful life events, the way that women perceive the severity of stress (worry) and appraise their own resources to cope with it (locus of control), as well as actual coping modes, and mental health problems. The results show that the Palestinian women had more personal and political worries, and showed more personal helplessness (external locus of control) after the Lebanon war in 1985 than in 1982. The results further show that women employed less avoidance and retreat, and less denial as coping modes in 1985 than in 1982. No changes between these years were found in the women's mental health, their locus of control on the Palestinian issue, and coping modes of aggressive action and social-political activity. The results on the roles of personal factors in the stress process show that younger women expressed more political worries and initiative (internal locus of control) on the Palestinian issue. Furthermore, women who had many children had fewer political worries and more personal worries, and were less external in their locus of control on the Palestinian issue than women with few children. PMID- 2233514 TI - Review of some studies of group behaviour relevant to global security. AB - Since the publication of Lionel Penrose's On the Objective Study of Crowd Behaviour, significant advances have been made in the understanding of intragroup and intergroup behaviour relevant to world security and peace. Some of these are reviewed in this article. Rational decisions in the complex and dangerous modern world may require understanding of the constraints and influence of both the cultural and biological backgrounds of human social existence. PMID- 2233515 TI - Security through co-operation. PMID- 2233516 TI - Clinical trial and pharmacokinetics of carboplatin 560 mg/m2 in children. AB - We report a clinical trial with carboplatin (CBDCA) in 15 children with malignant solid tumors recurrent after or resistant to conventional treatment. Based on previous phase I clinical trials, these children were given a dose of CBDCA 560 mg/m2 by intravenous infusion every 4 weeks. The study includes a pharmacokinetic analysis of CBDCA in three patients. This clinical trial shows the feasibility of this CB-DCA schedule, even after high cumulative doses of previous chemotherapy. As expected the main toxicity was hematologic but the risk of renal and ototoxicity is not excluded and these functions have still to be monitored when this relatively high dose of CBDCA chemotherapy is used. PMID- 2233517 TI - Prognostic significance of regional lymph node involvement in childhood extremity rhabdomyosarcoma. AB - Thirty-four patients with extremity rhabdomyosarcoma were treated at Memorial Sloan-Kettering Cancer Center during the years 1970 to 1987. The regional lymph node status at diagnosis was histologically confirmed in 27 patients. Of these 27 patients, there were 20 males and 7 females, ranging in age from 6 months to 22 years (median 10 years). The primary tumor was located in the upper and lower extremity in 11 and 16 patients, respectively. The histologic subtypes included embryonal in 13 patients and alveolar in 14 patients. Fourteen patients had no evidence of regional lymph node involvement (N0) and 13 patients had lymphatic metastases (N1). All patients were further staged according to the extent of surgical resection, the local invasiveness and size of the primary tumor, and the presence (M1) or absence (M0) of distant metastases. With a median follow-up time from diagnosis of 9.2 years (minimum 5.3 years), the overall survival was 48% (13/27): N0, 12/14 and N1, 1/13 (P = .0002). Excluding those patients with M1 disease, the survival rate was: N0, 11/12; N1, 1/10 (P = .0001). The first site of relapse in the M0 patients was distant metastases in 8/10 cases. Our results suggest that regional lymph node involvement at diagnosis is an important prognostic factor in extremity RMS. Its presence appears to be associated with a high incidence of relapse in metastatic sites and poor survival outcome. PMID- 2233518 TI - Decrease in childhood neuroblastoma death in Japan. AB - Death statistics cards under 15 years of age submitted between 1979 and 1987 and coded as malignant neoplasms of organs or sites, in which neuroblastoma might affect, were inspected. A total of 1,037 cases of neuroblastoma death were identified. Total number of neuroblastoma deaths among those under 15 years of age ranged between 118 and 145 from 1979 to 1984. However, after 1985 the number of deaths showed a declining tendency, down to 89 in both 1985 and 1986 and totalling only 93 in 1987. This declining tendency was mostly-seen among children between 1 to 4 years of age. In this age group, the rate of death in 1987 was about one half of that in 1979; In the other age groups no declining tendency of neuroblastoma death was found. The reason for the decrease in neuroblastoma death among children in Japan may be a result of widespread mass-screening for neuroblastoma. However, further study is necessary before any final conclusions can be drawn. PMID- 2233519 TI - Superior vena cava syndrome associated with childhood malignancy: analysis of 24 cases. AB - Twenty-four children with superior vena cava obstruction at initial presentation or associated with disease recurrence were treated at St. Jude Children's Research Hospital from 1973 to 1988. Of the 16 patients with superior vena cava syndrome at presentation, eight had non-Hodgkin's lymphoma, four had acute lymphoblastic leukemia, two had Hodgkin's disease, one had neuroblastoma, and one had a yolk sac tumor. Their clinical condition at presentation was often critical and required rapid treatment. In all cases, histopathologic diagnosis was obtained without complication by either bone marrow aspiration, lymph node biopsy, thoracentesis, or thoracotomy prior to the initiation of definitive therapy. Eight children had superior vena cava syndrome as a late complication during the course of their therapy. None had an antecedent history of superior vena cava obstruction. In contrast to the patients with superior vena cava obstruction at presentation, this group was composed predominantly of patients with recurrent solid tumors. Other causes included disseminated candidiasis and superior vena cava thrombosis, thus underscoring the importance of recognizing the etiology of superior vena cava syndrome to facilitate proper treatment. PMID- 2233520 TI - Phase II study of MOPLACE chemotherapy for patients with previously treated Hodgkin's disease: a CALGB study. AB - To further evaluate possible non-cross-resistant regimens in Hodgkin's disease, a phase II trial utilizing antimetabolites and etoposide was initiated by the Cancer and Leukemia Group B (CALGB). Etoposide was included because of its known efficacy in relapsed Hodgkin's disease and to evaluate for synergy with an alkylating agent and vincristine. Cytosine arabinoside and methotrexate were included to evaluate their effectiveness in rapidly growing resistant disease. Forty-two patients with previously treated Hodgkin's disease were entered, of which 37 are evaluable for response and toxicity. All patients had at least 2 prior regimens of chemotherapy and 59% had additional radiation therapy. Complete and partial response was observed in 61%; there were 32% complete responders. Duration of complete response was a median of 8 months (range 2-28+ months). Duration of partial response was 7 months (range 1-17 months). Three patients remain in complete remission at 19, 19, and 28 months. Major toxicity was hematologic with severe or life-threatening toxicity in 54%. There was one patient with a fatal infection. Non-hematologic toxicity, save for nausea and vomiting, was mild and uncommon. There were two fatal and one severe pulmonary toxicities reported in patients who had previous exposure to bleomycin and mediastinal radiation. Three had interstitial pneumonitis and one pulmonary emboli. The interstitial pneumonitis was thought to be drug related. Survival of the entire group is estimated at 61% at 12 months. We conclude that MOPLACE is an effective regimen with an appreciable complete response rate in this heavily pretreated group of patients. Hematologic and pulmonary toxicities are severe and may necessitate dose modifications. The use of etoposide containing combinations requires further study as primary therapy in untreated patients. PMID- 2233521 TI - Phase II trial of etoposide and doxorubicin in advanced head and neck cancer. AB - In an effort to improve the response rate of patients with advanced head and neck cancer, a clinical trial combining two infrequently studied drugs was conducted. Twelve patients with squamous cell carcinoma of the head and neck were treated with 3-day continuous infusions of etoposide (90 mg/m2/day) and doxorubicin (15 mg/m2/day). All patients had been heavily pre-treated with surgery, radiation therapy, and/or chemotherapy. No objective responses were observed in 9 evaluable patients. One patient maintained stable disease state for 4 months. The major toxicity was Grade 3 or 4 myelosuppression which occurred in 42% of administered cycles. Although single-agent etoposide and doxorubicin have shown response rates of 10%-40% in patients with squamous cell carcinoma of the head and neck, we were disappointed to find that the combination of etoposide and doxorubicin has little or no activity in patients with advanced head and neck cancer. The toxicity encountered with this combination was significant. PMID- 2233522 TI - Histological, immunohistochemical, and chromosomal studies on non-adrenal neuroblastomas without increased excretion of catecholamines and their metabolites in urine. AB - We reviewed our records for the last 10 years and found three of the 36 patients with neuroblastoma did not excrete significantly increased quantities of catecholamine metabolites in urine. All of these tumors were histologically characterized by small round cells and possessed a few dense core granules on the electron microscopic examination. All of them were reacted with anti-neuron specific enolase (NSE) antibodies, OKB2, PI153/3 monoclonal antibodies (MoAbs). The HNK-1, BA-1, and SJ-9A4 MoAbs reacted with two out of three. One of them demonstrated a reciprocal translocation involving the short arm deletion of chromosome 1. This multidisciplinary study has been helpful in making more accurate diagnoses for neuroblastoma without classical clinical characters. PMID- 2233523 TI - Non-randomised study comparing toxicity of Escherichia coli and Erwinia asparaginase in children with leukaemia. AB - Seven hundred fifty-eight unselected children entered into the United Kingdom Medical Research Council acute lymphoblastic leukaemia UKALL VIII Study and Trial were studied for differences in early treatment-related toxicity according to the type of intramuscular L-asparaginase received. Two hundred seventy-five received a product obtained from Escherichia coli and 483 the enzyme from Erwinia chrysanthemi. The E. coli patients had a significantly higher incidence of neurotoxicity, pancreatitis, and life-threatening sepsis (4%, 2%, and 20%, respectively) when compared with the Erwinia group (2%, 0%, and 18%). Severe hypersensitivity was seen in one patient from both groups and the incidence of glucose intolerance was not significantly different. These findings indicate that E. coli asparaginase may be more toxic. With a minimum follow up of 4 1/2 years there is no evidence that either product has made a significantly different contribution to disease-free survival. PMID- 2233524 TI - Non-Hodgkin's lymphoma in a cardiac transplant patient--successful management without chemotherapy. PMID- 2233525 TI - Breast nodules as the initial site of relapse in childhood leukemia. AB - Two children with acute monoblastic leukemia in remission developed breast nodules that were the initial sites of disease relapse. Shortly after the appearance of disease in this site, the children developed marrow recurrence and, despite additional treatment, rapidly deteriorated and died from pancytopenia related complications. The importance of careful breast examination is stressed as part of the surveillance physical examination for children with monoblastic leukemia. PMID- 2233526 TI - Gastric tumor and hematemesis in a patient with chronic lymphocytic leukemia. PMID- 2233527 TI - [Data on the epidemiology of Lyme disease in Bulgaria]. AB - 134 patients with clinically, epidemiologically and serologically confirmed Lyme's disease have been examined. 89.5% of them had erythema chronicum migrans, 112 patients (83.6%) were known to have had tick bites. The majority of patients were white-collar workers and townspeople. Hungry ticks collected from plants were shown to contain B. burgdorferi. 497 foresters and animal farmers have been serologically examined, using an indirect immunofluorescence test. Antibodies to B. burgdorferi in diagnostic titres have been revealed in 15.3% of foresters and 17.8% of animal farmers. PMID- 2233528 TI - [Data on the typing of natural foci of tick-borne rickettsiosis in Siberia and the Far East]. AB - The studies of the level of Ixodidae ticks infestation and seroepidemiological parameters made it possible to characterize specific features of the epidemic process in foci with different tick species. A working principle for the typing of the natural foci of tick-borne rickettsiosis has been suggested. According to the number of tick species 3 types of foci have been identified: monovector, divector and polyvector foci. PMID- 2233529 TI - [An analysis of the multiyear dynamics of ascariasis morbidity in the USSR]. PMID- 2233530 TI - [The current situation with strongyloidiasis in the USSR]. AB - The literary data available and our own observations served the basis for characterization on strongyloidiasis distribution areas in the USSR. They embrace the Caucasus, Middle Asia, the European part of the country up to latitude 55-56 degrees north in the Maritime Territory and the southern part of the Khabarovsk Territory. Intensive invasion foci in specialized hostel-type institutions, invasion importation from the tropics to moderate climatic zones and their role in the epidemic process are discussed. PMID- 2233531 TI - [Opisthorchiasis in Chernigov Province (the situation and control and prevention measures)]. AB - The results of planned population surveys for opisthorchiasis performed by teams of epidemiologists in 11 districts of Chernigov Province have been reviewed. 130,067 individuals in 156 communities have been examined. All the communities were situated not more than 5 km from the main water artery of the area--the Desna River and its main tributaries--the Seim, the Ubed', the Doch', the Borzna. 713 cases of opisthorchiasis have been identified in 96 villages. 1.0 +/- 0.2% (out of 3,180) of mollusks C. inflata and 0.9 +/- 0.4% of carps from the river basins in 8 districts of the region proved to be invaded with Opisthorchis larvae. PMID- 2233532 TI - [The characteristics of the circulation of the causative agent of opisthorchiasis in the tributaries of the Ob]. AB - Opisthorchiasis morbidity is reviewed in the area of the Vasyugan River, an Ob tributary. Intermediate hosts have been found in 3 settlements situated at various distances from the ostium. The infestation of intermediate and additional hosts with Opisthorchis larvae is investigated. The above data and the results of previous population surveys (establishing infestation and contamination) served the basis for elucidating the nature of helminth circulation on the territory along the Vasyugan River. The role of infected fish migration is discussed as a source of human infection in areas where helminth circulation is altogether absent or is at an extremely low level. PMID- 2233533 TI - [Alveolar hydatid disease in the Koryak Autonomous Okrug]. PMID- 2233534 TI - [The serum immunoglobulin E level and the endocrine activity of the stomach, duodenum and pancreas after recovery from opisthorchiasis]. AB - Serum IgE level and blood levels of gastrin, insulin, C peptide and glucagon have been studied in 34 patients with chronic opisthorchiasis (18 females and 16 males aged 36.5 +/- 2.6 years) prior to treatment and 10 days, 6 months and 12 months after recovery from the invasion. Blood levels of gastrin, insulin and C peptide remained unchanged. A trend towards normalization of glucagon levels about a year after recovery from opisthorchiasis has been observed. Serum IgE level a year after recovery was normal. PMID- 2233536 TI - [The decreased susceptibility of Syrian hamsters to Opisthorchis felineus invasion after its repeated administration]. AB - The investigations conducted on Syrian hamsters have revealed that multiple enteral infusions of cold inactivated (t = -10 degrees C) O. felineus metacercariae resulted in the formation of immunocompetent cell and fibroblast infiltrations around the branches of the portal vein. The infestation of animals by viable pathogens led to reduced accommodation of helminths and suppressed cell infiltration in the liver. It is assumed that the native population of the foci become tolerant to the disease with the penetration of noninvasive Opisthorchis larvae into their body and the development of latent forms of helminthiasis. PMID- 2233535 TI - [Cross-reacting antigens of Opisthorchis felineus and Salmonella typhi and their possible effect on the clinical course of typhoid fever]. AB - The experiments on rabbits immunized with a complex O. felineus antigen and spirit abdominal typhoid vaccine enriched with Vi-antigen, as well as studies on patients with chronic opisthorchiasis and bacterial carriers of S. typhi have established the presence of cross-reacting antigens in abdominal typhoid and opisthorchiasis pathogens. It is suggested that these antigens play an essential role in the development and outcome of abdominal typhoid secondary to chronic opisthorchiasis invasion. PMID- 2233537 TI - [A comparative study of the efficacy of praziquantel and its liposomal form in experimental opisthorchiasis]. AB - Intensive and extensive efficacy of praziquantel pure and that included in multilamellar liposomes was studied. As a result, a high anti-helminthic activity of liposomal praziquantel has been established. Negative effect of praziquantel on protein synthetic and enzymatic function of the liver has been revealed in normal animals. The treatment with liposomal praziquantel led to a rapid normalization of total lipid and bilirubin levels, thymol turbidity test, transaminase indices and also to a decrease in dystrophic liver changes. PMID- 2233538 TI - [The effectiveness of 2 immunoenzyme analysis test systems in the diagnosis of human trichinelliasis]. AB - The efficacy of 2 test systems for enzyme immunoassay using various ingredients (produced in the E. I. Martsinovskii Institute of Medical Parasitology and Tropical Medicine, USSR Ministry of Public Health and Institute of Advanced Medical and Pharmaceutical Training, Prague) has been assessed on blood sera of 122 patients with trichinellosis, 200 patients with other parasitic diseases and 300 healthy donors. No considerable differences in the efficacy of 2 test systems have been revealed. The test sensitivity is higher with the use of somatic than secretory-excretory antigens of identical specificity. PMID- 2233539 TI - [Antigenic preparations from Opisthorchis and their use in immunodiagnosis. 2. The effectiveness of antibody detection in infected patients]. AB - Serological studies using opisthorchis immunoreagents of various specificity (metabolic, somatic and from eggs) have shown that metabolic antigen preparations were the most effective. Simultaneous use of 3 immunoreagents of various specificity ensures higher percentage of opisthorchiasis patients' identification. Passive hemagglutination test and enzyme immunoassay are practically identically effective for the antibody determination. PMID- 2233541 TI - [The ultrastructure of sterile larvocysts of Echinococcus granulosus from different hosts]. AB - The sterile larvocysts of Echinococcus granulosus are characterized by host dependent morphological variability. The distinctions reside in the intensity of germinative layer development, glycogen and lipid content, ultrastructure of the tegument distal cytoplasm. The larvocysts obtained from one host species in different geographic zones of the country are morphologically similar. The sterile Echinococcus granulosus larvocysts obtained upon experimental infection of mice demonstrate typical morphological signs of the strain used for infection. PMID- 2233540 TI - [The clinical picture of tropical malaria in nonimmune newcomers in endemic foci in Africa]. AB - 415 nonimmune patients with acute signs and symptoms of falciparum malaria have been examined. The study has shown that 2/3 of patients had a moderate form of the disease, a severe form was noted only in 4.57% of patients. Classical symptoms of malaria--chill, body ache, headache--were observed only in half of the patients, 1/3 of patients had so-called masks of malaria--respiratory catarrh, pharyngitis, allergy, symptoms of enterocolitis. Early diagnosis and complex treatment with chloroquine or chloroquine combined with fansidar (1.16% of patients) promoted to a rapid improvement of the clinical symptoms and to favourable outcome. No fatal outcomes or severe complications have been observed. The mean duration of the disability period was 8.9 days. The first-degree resistance to chloroquine (clinical data) was noted in 11 patients, repeated manifestations of malaria occurred in 8.12% of patients and were more severe. PMID- 2233542 TI - [The Wilcoxon nonparametric statistical criterion in the Mann-Whitney modification in evaluating the results of parasitological health research]. PMID- 2233543 TI - [Invention activities and the structure of conducting patent research at the E. I. Martsinovskii Institute of Medical Parasitology and Tropical Medicine. The tasks of the Patent Service of the Institute]. PMID- 2233544 TI - [The first Russian expedition to Brazil in 1821-1829 (the medical parasitological aspects)]. PMID- 2233546 TI - [Ecology and health]. AB - The World Health Organization (WHO) has proclaimed 1990 as the year of human environment protection. A tight bond between ecology as a science, and preventive medicine has been observed. The paper presents the basic facts about ground, water and air pollution, as well as the effects of ecological disorders on human health. Noted are the basic pointers for the improvement of the conditions in our environment and the role that society and the individual, especially a physician has to carry. Everybody should act accordingly with the proclaimed slogan: Think global--Act local. PMID- 2233545 TI - [The efficacy of and tolerance for fansimef in the treatment of tropical malaria in the south of the Socialist Republic of Vietnam]. AB - The efficacy of and tolerance to fancimef in 49 patients was compared to the efficacy of and tolerance to quinine in combination with fansidar in 33 patients with moderate P. falciparum malaria. A good tolerance to and a high efficacy of fancimef have been shown, which was manifested in rapid fever arrest, disappearance of parasitemia, absence of the disease relapses, which were observed in 2 patients on quinine combined with fansidar. The advantage of fansimef is one-time administration of the total course dose. PMID- 2233548 TI - [The importance of monitoring with the Swan-Ganz catheter in cardiac surgery- personal experience]. AB - In our paper we will present the advantages of the modern hemodynamic monitoring system in open heart surgery, especially in high risk patients. The Swan-Ganz monitoring system, with great possibilities for measuring and calculating a large number of parameters, is necessary for the postoperative treatment, for regular diagnosis and therapy of heart insufficiency, as well as the low cardiac output syndrome. There is no correlation between pulmonary capillary wedge pressure and central venous pressure, and central venous pressure isn't significant for heart insufficiency estimation, more exactly left heart insufficiency estimation. Pulmonary capillary wedge pressure is significant in the prevention and therapy of the low cardiac output syndrome. PMID- 2233547 TI - [Ecological characteristics of viral hepatitis. III. Hepatitis B in Vojvodina]. AB - The significance of particular risk factors for hepatitis B virus infection in persons of various ages was analyzed by active epidemiological investigation. Among the diseased children, the largest number of them were mentally retarded and accommodated in special institutions. Sexual and professional exposure to the hepatitis B virus is responsible for a considerable percentage of diseased adults, aged 20-49. In persons over 50 years of age, parenteral medical interventions are the most frequent risk factor. By carrying out proper sterilization in medical practice and vaccination of the exposed categories of the population, a significant reduction of the hepatitis B morbidity rates can be achieved. PMID- 2233549 TI - [Morphometric analysis of the vascular network of the suprachiasmatic and paraventricular nucleus in the human brain]. AB - The aim of the study is to discover, the sources of vascularization, vascular areas, the size and density of the capillary network in the suprachiasmatic and the paraventricular nuclei of postnatal human brains of both sexes. The brain blood vessels under examination were filled with a mixture of India ink and gelatin. The serial paraffin sections of 200 microns cleared after Spalteholz. In the vascularization of the suprachiasmatic and the paraventricular nuclei, two arterial stems, take part with their branches (a. cerebri anterior and a. communicans anterior). In order to quantify the density of the capillary network, the authors used the standard stereologic parameters - volume density, surface density and mean radius of blood vessels. The comparative testing of the mean values obtained in male and female subjects did not reveal any significant sex - dependent differences regarding the size and density of the capillary network in the suprachiasmatic and the paraventricular nuclei of the human brain. PMID- 2233550 TI - [Psychological changes in diabetic patients with polyneuropathy]. AB - The study has multi-sidedly examined and considered the possible relations between psychic, especially unsuitable emotional charges and the most frequent peripheral nerve complications in diabetes mellitus patients. By the comparative method of researching the psychic status and electro-physiological characteristics in patients with diabetic polyneuropathy, it has not been determined that distinct psychic disorders exist in patients with roughly expressed nervous complications in relation to the control group on condition, which consists of patients with complications of a lighter form. The results of this research lead the assumptions, of a possible psychic induction of nervous complications in the course of diabetes mellitus, to a doubt. PMID- 2233551 TI - [Social tension--a factor in conversion. Case report]. AB - Presented is a case of a girl of Albanian nationality, an adolescent, one of the ill in the group of "mass poisoned" in Kosovo, at the beginning of 1990. The up to then, completely healthy girl had repeated crises of the same type four times, with functional disorders. She was hospitalized at the request of her father in Novi Sad, at the Institute for Neurology and Psychiatry of the Developmental Age. The somatic and laboratory findings were within the average limits. The psychological tests indicated a person prone to conversive reacting in situations which she does not succeed to process emotionally in an adequate manner. Such a personality structure had the role of inducing a conversive atmosphere in the immediate school environment. The presented case has suggested that a low level of general culture and expected school knowledge primarily creates favorable grounds for massive hysterical occurrences. PMID- 2233553 TI - [Fluoridation of drinking water in Pancevo]. AB - In Pancevo on May 12, 1988 the continual fluoridation of water was started. Fluoridation is conducted with 2% silicofluoride acid. Up to now, controls on fluoride content in drinking water, which are conducted on eight places in the city, show that the concentration of fluoride is about 1 mg of fluoride per liter of drinking water. There are very little deviations during measurement, so the system can be considered as safe. The analysis of costs of water fluoridation in October 1988 was 250 dinars per inhabitant. In this way we achieved the most efficient and at the same time cheap method of dental health protection as well as the protection of the whole human organism, in accordance with the opinions of the World Health Organization concerning that subject. PMID- 2233552 TI - [Acute gastrointestinal hemorrhage after placement of a peritoneojugular shunt]. AB - Since 1984 the peritoneovenous (LeVeen) shunt has been installed in 33 patients (10 females 30.3%, and 23 males 69.7%), with the average age of 54 +/- 8 years all in the oedema--ascitic decompensation phase of their primary illness. The control group consisted of 39 patients with identical etiology and primary illness stadium, sex and age structure and duration of primary illness, all treated with medicament - diet therapy. All the operated patients and those treated with medicament--diet regime died. Their autopsy findings were confronted. The aim of this study was to indicate the type and frequency of digestive hemorrhage in this population on our own clinical--patient material. Gastrointestinal hemorrhage was the cause of death in 8 (24.24%) patients out of the group operated on, and 6 (15.3%) from the control group. The isolated rupture of esophageal varices was the cause of death in one (3.03%) patient out of the group operated on, and in 5 (12.12%) patients from the control group, the rupture of esophageal varices with toxic vasculitis in 3 (0.09%) patients from the group operated on, and not in one out of the control group; rupture of esophageal varices associated with toxic vasculitis and disorders of the hemostatic mechanism appeared in 4 (12.12%) of patients from the group operated on, and in 1 (2.56%) of the control group. On the basis of the presented it can be concluded that gastrointestinal hemorrhage is a significantly more frequent cause of death in the group operated on than in the control group, and that hemorrhages are of an all the more complex etiology when the flow-in of ascites into circulation is greater. Hemodilution and endotoxins are to blame for their occurrence and it is necessary to preoperatively conduct, beside the control of the hemostatic mechanism, also the test of ones own ascitic burdening and to determine the level of endotoxin in the ascites. PMID- 2233554 TI - [Analysis of the causes of suicide attempts in women]. AB - In suicidological literature and practice there is a repeated confirmation of the presence of the appeal function as an unconscious motive in the suicide attempt. In the basis of the appeal is the attempt of the suicidant to restore disturbed relations with surroundings, and according to this, in this case, the suicide attempt is directed more to life than death. In the researched material an analysis was conducted of the cause of death in 319 women with the aim to evident the possible presence of unwanted pregnancy and to give light to the causes and motives of the act of suicide. PMID- 2233555 TI - [Hypoglycemia in childhood. I. Physiology, pathophysiology and the classification of hypoglycemia]. AB - Regardless of age and body mass, hypoglycemia is defined as the glycemia value below 2.6 mmol/l. This is the borderline glycemia value, below which the suffering begins which directly endangers the CNS development in the newborn period. The fact that we registered hypoglycemias in 2/3 of premature infants and in 3/4 of low birth weight infants at registration on the ward for premature infants at the Institute for Mother and Child Health Protection, in the course of 1988, tells of the complexity and seriousness of the situation with which we meet during the depopulation of the inhabitants. The paper gives physiological basics for the understanding of glucose homeostasis in the organism, as the most frequent forms of hypoglycemia with which the physician meets in practice. A diagnosing and hypoglycemia treatment algorithm is given. PMID- 2233556 TI - [Rehabilitation of the rheumatoid hand]. AB - Treatment of patients suffering from rheumatoid arthritis is complicated and it consists mainly of applying general measures, medical therapy, physical therapy and rehabilitation, and, if necessary, surgical - orthopedic measures. The treatment is conducted as team work and it lasts for years. The chronic and evolutionary character of the disease requires a rather dynamic effort against the onset of joint deformation as well as the constant follow up of the evolution of the disease, and the local condition of the joints. Within the examined group of a hundred patients with classical and definitive rheumatoid arthritis, formed deformations of hand joints were registered in 72% of patients by means of clinical examination. Preventive measures against joint deformation make an integral part of rheumatoid arthritis patient treatment. Their application starts from the moment when the diagnosis is made and lasts as long as the disease does. PMID- 2233558 TI - [Regulation of muscle tonus]. AB - The regulation of muscle tonus takes place at least at six levels of the central nervous system: the spinal cord, vestibular nuclei, the cerebellum, the reticular formation, extrapyramidal system and the motor cortex. A multiple complexity of the connections of these systems in the regulation of muscle tonus is presented, so that therapy can be usefully applied in states of muscle tonus disorders. PMID- 2233557 TI - [Clinical and radiologic status of the hip joint in adolescents and children with late detection of anomalies of the hip joint]. AB - The study analyzed 35 questionnaires (70 hips) with an overdue discovered anomaly of the hip joint. 32 cases (91.5%) were girls, 3 cases (8.5%) boys, while the relation of girls to boys was 10.6:1. The average age at the moment of discovery of the defect was 3.9 months and in the period of control 12-13 years. All the questionnaires were conservatively treated but it was not observed that the method of treatment had any influence on the final result. According to analysis of clinical and radiological parameters the authors accepted the thought that these hips should be followed up until the end of their growth, and when an indication for operative treatment has been set it should take care about the development of the acetabulum as well as the shape of the proximal edge of the femur and the orientation of the ilium bone. PMID- 2233559 TI - [Organic factors in behavior disorders in the developmental age]. AB - The problem of bad behavior in the young is as old as the written history of mankind. It is always a current problem in a practical and theoretical sense as well. While everyday life is filled with various forms of criminal offense, drug addiction, the forming of gangs-especially in dynamic societies, theoretical opinions tend to oscillate between biological factors and the psychological social ones which are always unsuitable for a person in the course of its development. The authors have presented a review of the basic theoretical directions, and after that the results of their own research. Children with behavior disorders were investigated: parallely by psychological-psychiatric investigation as well as with an up-to-date biological approach, examining subclinical semiotics, EEG and REG. On the basis of these comparisons we have come to the following principal opinions: the suggested psycho-neuro-vegetative subclinical syndrome, recommended by the same authors, does not take the behavior disorder upon itself. Also, not every behavior disorder includes the obligatory psycho-neuro-vegetative subclinical syndrome (PNVSS). Nevertheless, PNVSS presents a risk factor for behavior disorder, in the case that the personality in development is growing up under unfavorable psycho-social conditions. Finally, in the younger ages PNVSS, by its primary features, determines the behavior disorder also, while at an older age (after 11) behavior has all the more of an asocial and antisocial character. PMID- 2233560 TI - [The 88th anniversary of the Novi Sad Iodine Spa]. PMID- 2233561 TI - Random sampling for evaluating treatment plans. AB - We analyze the influence of sampling technique on the accuracy of estimating irradiated volumes, dose-volume histograms and tumor control and normal tissue complication probabilities. The sampling techniques we consider are uniform distribution of points on a regular Cartesian grid and random selection of points. For three-dimensional treatment planning, random sampling leads to a significant reduction in estimation error and/or in the number of calculation points necessary to achieve a required accuracy. We discuss advantages and drawbacks of random sampling, as compared to sampling on a regular grid. It is suggested that, in practical situations, at least 50 times fewer randomly sampled points per organ/volume of interest are needed for fast estimation of complication probability with the same accuracy, i.e., not exceeding 5% (within 95% confidence limits) in the worst case. PMID- 2233562 TI - Therapy imaging: a signal-to-noise analysis of a fluoroscopic imaging system for radiotherapy localization. AB - We have been developing a digital fluoroscopic imaging system to replace the portal films that are currently used to verify patient positioning during radiotherapy treatments. Our system differs from previously reported devices in the construction of the detector and in the operation of the TV camera. The signal, noise, and signal-to-noise properties of this system have been determined by measuring the modulation transfer function [MTF(f)], the noise power spectra [NPS(f)], and by calculating the detective quantum efficiency [DQE(f)] of the system. The results show: (i) that the spatial resolution of the system is determined largely by the lens of the TV camera and by frame grabber; and (ii) that the noise in the system is dominated by the secondary light quanta, due to the poor light collection efficiency of the optical chain. Despite these physical limitations, a contrast-detail study shows that the fluoroscopic system is better at detecting large, low contrast objects than portal films. Therefore the system is already a reasonable alternative to portal films and modifications to the metal plate/phosphor detector, lens, TV camera, and frame grabber should improve the performance of the system further. PMID- 2233563 TI - Forward-directed bremsstrahlung of 10- to 30-MeV electrons incident on thick targets of Al and Pb. AB - Bremsstrahlung spectra from thick targets of Al and Pb have been measured absolutely (photons per incident electron) along the beam axis for electrons of 10-, 15-, 20-, 25-, and 30-MeV incident energy. The spectra have a 220-keV low energy cutoff. The targets were cylinders with nominal thicknesses of 110% of the electron CSDA range. A thin transmission detector, calibrated against a toroidal current monitor, was placed upstream of the target to measure the beam current. The spectrometer was a 20-cm diameter by 25-cm-long cylindrical NaI detector. Measured spectra were corrected for pile-up, background, detector response, detector efficiency, attenuation in materials between the target and detector and the collimator effect. Spectra were calculated using the EGS4 Monte Carlo system for simulating the radiation transport. The simulation model included the small amount of material upstream of the target. This material contributed about 40% of the spectrum, but its presence or absence had little effect on the calculated bremsstrahlung yield. The shapes of the measured and calculated spectra were in excellent agreement. The ratio of the total number of photons in each measured spectrum to those in the corresponding calculated spectrum varied from 0.97 +/- 0.06 to 1.12 +/- 0.06, depending largely on the atomic number of the target. Absolute spectral measurements in the literature agreed with our calculations of spectral shape but showed a range of +/- 30% in the number of photons per incident electron relative to the calculated values, which is contrary to our result. PMID- 2233564 TI - Effect of tissue inhomogeneity on dose distribution of point sources of low energy electrons. AB - Perturbation in dose distributions of point sources of low-energy electrons at planar interfaces of cortical bone (CB) and red marrow (RM) was investigated experimentally and by Monte Carlo codes EGS and the TIGER series. Ultrathin LiF thermoluminescent dosimeters were used to measure the dose distributions of point sources of 204Tl and 147Pm in RM. When the point sources were at 12 mg/cm2 from a planar interface of CB and RM equivalent plastics, dose enhancement ratios in RM averaged over the region 0-12 mg/cm2 from the interface were measured to be 1.08 +/- 0.03 (SE) and 1.03 +/- 0.03 (SE) for 204Tl and 147Pm, respectively. The Monte Carlo codes predicted 1.05 +/- 0.02 and 1.01 +/- 0.02 for the two nuclides, respectively. However, EGS gave consistently 3% higher dose in the dose scoring region than the TIGER series when point sources of monoenergetic electrons up to 0.75 MeV energy were considered in the homogeneous RM situation or in the CB and RM heterogeneous situation. By means of the TIGER series, it was demonstrated that aluminum, which is normally assumed to be equivalent to CB in radiation dosimetry, leads to an overestimation of backscattering of low-energy electrons in soft tissue at a CB-soft-tissue interface by as much as a factor of 2. PMID- 2233565 TI - Anthropomorphic radiation therapy phantoms: a quantitative assessment of tissue substitutes. AB - Compositional analyses of samples of soft tissue and lung substitutes used in the construction of anthropomorphic radiotherapy phantoms were performed for products from Alderson Research Laboratories Inc., Kyoto Scientific Specimens Company/Capintec Inc., Humanoid Systems Inc., Radiology Support Devices Inc., and The Phantom Laboratory Inc. To assess quality control in the manufacture process, the results of these compositional analyses were compared with individual manufacturer's design specifications and electron densities measured by computed tomography analysis of actual phantom slices. A comparison of the manufacturers design specifications against reference tissue parameters from Tissue Substitutes in Radiation Dosimetry and Measurement (International Commission on Radiation Units and Measurements) indicates marked differences in the basic design of commercially available anthropomorphic phantoms. PMID- 2233566 TI - On methods of inhomogeneity corrections for photon transport. AB - Eight methods of photon inhomogeneity correction were examined for their photon transport approximations. The methods were categorized according to the different approaches used to model scatter photon dose contribution. They were the ratio of TAR (RTAR) and the modified Batho power law which utilized only the 1-D density information along the primary photon path; the equivalent TAR (ETAR) and the FFT convolution methods which incorporated the 3-D density information of the medium for empirical scatter dose calculation; the differential SAR (DSAR), the delta volume (DV), dose spread array (DSA), and differential pencil beam (DPB) methods which employed explicit 3-D scatter ray-trace calculation. Cobalt-60 measurements in horizontal slab phantoms were used to allow simpler data analysis. RTAR consistently overestimated lung corrections by approximately 10%. The scatter ray trace approach was not always better as the DSAR calculations were inferior to those using the Batho method. The ray-tracing DV, DPB, and DSA methods agreed with measurements mostly to within 2%, at the expense of long computation time. The nonscatter ray-tracing ETAR and FFT convolution calculations were only slightly inferior in the same geometries. These methods improve on the current 1 D methods and should be seriously considered for fast optimization purposes in practical 3-D treatment planning. PMID- 2233567 TI - Dose rate determination for 125I seeds. AB - Dose rates in water have been determined for the two types of 125I seed currently used in brachytherapy. The need for such determinations became evident when water/air ratios measured with a silicon diode were found to be lower than expected. Extensive measurements using lithium fluoride thermoluminescent dosimeters (TLD's) have been performed in a solid water phantom, at distances from 0.1 to 10 cm from the seed center and at angular increments of 10 degrees, 15 degrees, or 30 degrees within a plane through the seed axis. Dose calibration of the TLD's was accomplished by irradiation in air with 125I seeds of the same type and of strengths traceable to a calibration at the National Institute of Standards and Technology (NIST). Relative calibration of TLD's was monitored by irradiation, in an oven-type x-ray machine, of control dosimeters simultaneously and all dosimeters intercurrently with the 125I irradiations. Values obtained for the dose rate constant, i.e., dose rate per unit air-kerma strength at 1 cm on the transverse axis, were 0.853 and 0.932 cGy h-1 U-1 (1.08 and 1.18 cGy h-1 mCi 1) for the 6711 and 6702 seeds, respectively. Measured data were supplemented with Monte Carlo-calculated relative dose rate data generated using the MORSE code. These calculations used 100 energy groups from 10 to 35.4 keV and involved energy collection bins ranging from 0.025 to 1.2 cm on an edge. Normalized at 1 cm, transverse axis calculated data are not significantly different from measured data (ours or cited literature) at distances either less than 2.5 or greater than 8 cm. Normalized at different distances along the transverse axis, our off-axis calculated and measured distributions agree closely at all angles but differ from literature measured distributions at small (less than or equal to 1 cm) distances and, for small angles, increasingly at larger distances (greater than or equal to 5 cm). PMID- 2233568 TI - Dose distribution of 125I sources in different tissues. AB - The low-energy photons of 125I deposit energy in tissues primarily by the photoelectric effect, which is strongly dependent on the atomic number Z. Thus dose distributions of 125I sources in media of different Z are not the same. LiF and CaF2 thermoluminescent dosimeters were used for relative dose distribution measurements in materials that are equivalent to muscle, breast, and bone. The experimental data are in good agreement with published results for muscle, and in reasonable agreement with Monte Carlo calculations for all the tissues tested. These measured data provide the basis for dose distribution calculations when 125I seeds are implanted in or near inhomogeneous tissues. PMID- 2233570 TI - Film dosimetry analyses on the effect of gold shielding for iodine-125 eye plaque therapy for choroidal melanoma. AB - One of the methods currently being used to treat choroidal melanoma employs an episcleral plaque containing I-125 radioactive seeds. However, comprehensive dosimetry studies on the plaque are scarce and controversial. For this work, we use film to study the dosimetry outside the lip of the gold shield of the eye plaque. This lip around the gold shield was made to protect the critical structures behind and adjacent to the lesion. Since the changes of energy spectrum of I-125 in tissue are negligible, film dosimetry seems to be a logical choice because of high spatial resolution required around the lip of the gold plaque. For this study, we first established an H and D curve with dose expressed in a unit of specific dose rate constant. This avoids absolute dose measurements. All film density measurements are made with a 1-mm aperture scan, normalized to the density at the prescription point for tumor of 3-5-mm apical height, i.e., 5 mm from the interior surface of sclera, and converted to percentage isodose curves. With a gold shield, it is found that when the plaque is placed against the optical nerve, the optical disk and macula, located at 2 mm outside the lip, on the exterior surface of sclera, may receive 85% of the prescription dose for a 12-mm plaque and 58% for a 16-mm plaque. For tumors of 8-mm apical height, the optical nerve would receive more than the prescription dose. PMID- 2233569 TI - A dose computation model for 241Am vaginal applicators including the source-to source shielding effects. AB - A dose computation model has been developed for the determination of dose distributions around vaginal plaque applicators containing encapsulated 241Am sources. Encapsulated sources of 241Am emit primarily 60-keV photons which have a half-value layer thickness of 1/8 mm of lead. This makes possible highly effective in vivo shielding of normal tissues at risk, by placing thin lead shields at appropriate places on the applicator. However, self-absorption of photons in the source material itself is intense, requiring bulky sources of about 1 cm diameter. These sources also produce considerable source-to-source shielding which must be taken into account in dose calculations. Our dose computation model for a single source employs three-dimensional integration of dose contributions from volume elements of the source including the effects of absorption and scattering of photons in the source material, titanium encapsulation, and water. An empirical correction to Berger's data on buildup factors of point, isotropic sources is made to account for the effects of anisotropic photon emission by cylindrical 241Am sources. The second part of our dose computation model takes into account source-to-source shielding effects on both primary and scattered photons for the vaginal plaque geometry. The results of the model have been verified for accuracy by comparisons with extensive dosimetry measurements using lithium fluoride thermoluminescent dosimeters. PMID- 2233571 TI - Line and slice selection for moving spins. AB - The Bloch equations are solved numerically for spins moving at constant velocity for the case of 90 degrees slice selection, and for subsequent 180 degrees spin echo line selection. The calculations use the comoving, rotating reference frame which is shown to be valid for general accelerated motions. Magnetization profiles and phase shifts are presented for slice selection for both plug and laminar flow. Line selection is studied for the case of plug flow, where a "local vector sum" is introduced to demonstrate effective localization of activated spins. In addition to local magnetization densities, the spatially integrated signals seen by a nonselective antenna are calculated. The relation between net phase shift and flow rate is examined and deviations from the predictions of simple analytic models are discussed. PMID- 2233572 TI - Hyperthermia system combined with a magnetic resonance imaging unit. AB - Magnetic resonance imaging (MRI) has recently been proposed as a method to monitor, noninvasively, temperature, blood flow, and cell metabolism during oncologic hyperthermia (HT). To heat and "image" simultaneously, it is necessary to combine a HT device and a MRI unit. As a demonstrative example of the problems associated with implementing such a system, a mini-annular phased array hyperthermia applicator was combined with a 0.5-T whole body MRI unit. With the aid of filters, baluns, and switches, the HT applicator and the MRI unit were made compatible. The overall system was tested using a muscle-equivalent, cylindrically shaped polyacrylamide gel phantom. No interference between the HT device and the MRI unit was observed. Noninvasive temperature images, with a resolution better than 1 degree C/cm, were obtained from images of molecular diffusion recorded before and during heating. PMID- 2233573 TI - Computerized detection of pulmonary nodules in digital chest images: use of morphological filters in reducing false-positive detections. AB - Currently, radiologists can fail to detect lung nodules in up to 30% of actually positive cases. If a computerized scheme could alert the radiologist to locations of suspected nodules, then potentially the number of missed nodules could be reduced. We are developing such a computerized scheme that involves a difference image approach and various feature-extraction techniques. In this paper, we describe our use of digital morphological processing in the reduction of computer identified false-positive detections. A feature-extraction technique, which includes the sequential application of nonlinear filters of erosion and dilation, is employed to reduce the camouflaging effect of ribs and vessels on nodule detection. This additional feature-extraction technique reduced the true-positive rate of the computerized scheme by 13% and the false-positive rate by 50%. In a comparison of the scheme with and without the additional feature-extraction technique, inclusion of the additional technique increased the detection sensitivity by about half at the level of three to four false-positive detections per chest image. PMID- 2233574 TI - Single-exposure dual-energy computed radiography. AB - This paper focuses on analysis and development of a single-exposure dual-energy digital radiographic method using computed radiography (Fuji FCR-101 storage phosphor system). A detector sandwich consisting of storage phosphor imaging plates and an interdetector filter is used. The goal of this process is to provide a simple dual-energy method using typical plane-projection radiographic equipment and techniques. This approach exploits the transparency of the storage phosphor plates, using radiographic information that would be otherwise lost, to provide energy selective information essentially as a by-product of the radiographic examination. In order to effectively make use of the large dynamic range of the storage phosphor imaging plates (10,000:1), a computed radiography image reading mode of fixed analog-to-digital converter gain and variable photomultiplier sensitivity provides image data which can be related to relative incident exposure for export to the decomposition algorithm. Scatter rejection requirements necessitated crossed 12:1 grids for a field size of 36 x 36 cm. Optimal technique parameters obtained from computer simulation through minimization of the aluminum and Plexiglas equivalent image uncertainty under conditions of constant absorbed does resulted as: 100 kVp using a 0.15-mm-thick tin (Sn) interdetector filter for the lung field. This yields a surface exposure of 23 mR and a surface absorbed dose of 0.26 mGy for a 23-cm-thick chest. Clinical application in evaluation of the solitary pulmonary nodule is discussed, along with an image set demonstrating this application. PMID- 2233575 TI - A time-delay integration charge-coupled device camera for slot-scanned digital radiography. AB - We have developed a low-noise digital camera based on a 512 x 96 element CCD operating in the time-delay integration mode. This camera has been combined with an x-ray image intensifier to record radiographic images produced by a scanning slot beam of radiation. This results in the rejection of a large fraction of scattered radiation, without a significant increase in x-ray tube heat loading or image acquisition time. Here we describe the design of our CCD camera and the results of our investigations of camera resolution, linearity, noise, and quantum efficiency. We have found that both the resolution limit (50 mm-1) and the dynamic range (2100) of this novel camera are greater than reported values for conventional video cameras. Applications of this system in digital angiography and mammography are discussed. PMID- 2233576 TI - Effect of various noise sources on the detective quantum efficiency of phosphor screens. AB - We have examined the effect of screen-structure, optical-detector, and secondary quantum noise sources on detective quantum efficiency, DQE(f). This was done by using experimental measurements of screen-structure and optical-detector noise in combination with a theoretical model which predicts x-ray quantum and secondary quantum noise for different optical and physical properties of a phosphor screen. The reduction in DQE(f) from noise sources other than x-ray quantum noise depends on the noise power spectra (NPS) of these other sources relative to the x-ray quantum NPS. Even though x-ray quantum noise may be the dominant noise source at low spatial frequencies, it decreases relatively rapidly with increasing frequency so that other noise sources, which may be small at low frequencies, dominate. Our model predicts that DQE(f) can be increased, at spatial frequencies less than 4 mm-1, by changing the optical properties of the screen even though modulation transfer function MTF(f) may decrease. Furthermore, if screen and optical-detector noise decrease with increasing frequency and secondary-quantum noise sufficiently small, then DQE(f) will also be improved at frequencies greater than 4 mm-1. PMID- 2233578 TI - Effects of nonmineral tissues on measurement of bone mineral content by dual photon absorptiometry. AB - Computer simulations were performed to investigate the effects of nonmineral tissue (overlying soft tissue and nonmineral components of bone) on the measurement of bone mineral content by dual-photon absorptiometry (DPA). Selected experimental studies were performed to test the predictions of the simulations. The results indicate that variations in the composition of nonmineral tissue can significantly affect measurement precision and accuracy at the levels achievable with modern x-ray based absorptiometry systems (0.5%). Thus biological variables may limit further improvements in measurement precision and accuracy. Biological variables also can affect intercalibration of systems that use different radiation sources and/or calibration techniques. PMID- 2233577 TI - Model of the spatial-frequency-dependent detective quantum efficiency of phosphor screens. AB - We have developed a theoretical model to predict the modulation transfer function (MTF), the shape of the x-ray quantum noise power spectrum (NPS), and the spatial frequency-dependent detective quantum efficiency (DQE) of an x-ray phosphor screen. The transfer of energy through the screen is modelled as a series of cascaded stochastic processes assuming that the screen consists of many thin phosphor layers. In this way, the model is able to account for the possibility of secondary-quantum noise and the difference in shape between MTF2 and the x-ray quantum NPS. Modelling a Kodak Min-R screen we were able to predict both the number of light quanta emitted per absorbed x-ray and MTF(f) to better than +/- 5%, and the scintillation efficiency to within 10% of experimentally measured values. The shape of the x-ray quantum NPS is predicted to within +/- 5% for spatial frequencies less than about 6 mm-1 and to within +/- 20% for higher frequencies. PMID- 2233579 TI - Origins of flare in x-ray image intensifiers. AB - The disk spread function of flare of an x-ray image intensifier (XRII) was measured using monoenergetic x rays. The signal-to-noise ratio at the center of the disks and the pulse height spectrum of the flare are also measured. These measurements are correlated with the physical construction of the XRII. A simple model of the XRII is developed which is used to identify the various sources of flare. PMID- 2233580 TI - Some possible effects of a catheter on the arterial wall. AB - When a catheter is inserted through an artery, the wall shear stress increases and the secondary flow exhibits an increased number of instantaneous vortices. These effects become more evident when the annular gap between the catheter and the artery becomes more narrow. Accordingly it is suggested that these factors may affect the preferential distribution of the atheromatous plaques at the sites of the wall with an increased permeability. PMID- 2233581 TI - Lesion detection in radiologic images using an autoassociative paradigm: preliminary results. AB - An area of artificial intelligence that has gained recent attention is the neural network approach to pattern recognition and classification. The use of neural networks in radiologic lesion detection is explored by employing what is known in the literature as the "novelty filter." This filter uses a linear algebraic model, whereupon in neural network terms, images of normal patterns become "training vectors" and are stored as columns of a matrix. An image of an abnormal pattern is introduced and the abnormality or the "novelty" is extracted. A noniterative technique has been applied. In a preliminary experiment, autoassociative recall was tested using alphabetic characters as training vectors. The second experiment used sections of transverse magnetic resonance (MR) images (TR = 3000 ms, TE = 40 ms) of normal patients as the training vectors. A section of a transverse MR brain image with multiple sclerosis lesions was introduced to the filter and the abnormalities were extracted. In conclusion, a neural network based lesion detector may have great promise in medical pattern recognition. PMID- 2233582 TI - Improving precision and safety in the use of beam modifying devices in radiation therapy. AB - Reliable and safe implementation of beam modifying devices such as wedges and block trays requires careful design and construction. Inappropriate design may pose problems ranging from user-hostile operation to hard-to-track, but significant variations in actual position in a beam. This may cause variation in actual wedge output factors, or variation in the position of a block tray. In case of simple mechanical failure or personnel mistake, design related mechanical conditions may result in injury to either a patient or a staff member. This paper is based on experience with linear accelerators from one manufacturer, but similar conditions are likely to exist with other radiation machines. A simple technical modification is offered which improves both accuracy and reproducibility in the placement of wedge-type filters. For our machines the solution also provides improved safety in the use of both wedge trays and block trays. PMID- 2233583 TI - A proposal for the calibration of plane-parallel ion chambers by accredited dosimetry calibration laboratories. AB - A procedure is described by which the AAPM-accredited dosimetry calibration laboratories could offer calibrations of plane-parallel ionization chambers for radiotherapy dosimetry applications, by comparison with a cylindrical ion chamber in a phantom irradiated by 60Co gamma rays. Ngas can thus be determined for the plane-parallel chamber under uniform conditions of photon scatter, and without the need for an electron fluence correction. PMID- 2233584 TI - Problems with the Radiation Measurements Incorporated/American College of Radiology mammography accreditation phantom. PMID- 2233585 TI - Assessment of 125I clinical dose specification from recent dose rate evaluations. PMID- 2233586 TI - Evaluation of the Crohn's Disease Activity Index (CDAI) and the Dutch Index for severity and activity of Crohn's disease. An analysis of the data from the European Cooperative Crohn's Disease Study. AB - In the European Cooperative Crohn's Disease Study a general documentation of clinical and laboratory data was made at the entry into the study in 452 patients. These patients were in different states of their disease from quiescent to very active. In all patients the Crohn's Disease Activity Index of Best (CDAI) and the Dutch Index of van Hees was calculated. Three gastroenterologists did a global clinical rating and a separate laboratory rating without knowledge of the indices. The ratings were then correlated with the indices in the individual patients. The clinical rating correlated well with the CDAI (r = 0.88) and less with the Dutch Index (r = 0.672). On the other hand the laboratory rating showed a better correlation with the Dutch Index (r = 0.742) than with the CDAI (r = 0.573). This demonstrates that the CDAI preferably is an estimate of the clinical severity of the disease and not of the activity of inflammation. Vice versa the Dutch Index is mainly reflecting the activity of the inflammatory process. PMID- 2233587 TI - [Sonographic percutaneous drainage of liver abscesses]. AB - 13 patients with pyogenic liver abscess and five patients with amoebic abscess underwent percutaneous drainage of the abscesses using the Seldinger (n = 8) or trocar technique (n = 11). The results showed that the trocar method was easier and faster to perform and well tolerated by the patients. No complications were observed despite of one case of transient peritonitis caused by a dislocated catheter. One patient with pyogenic liver abscess died of septic shock. All other patients were successfully treated, using local drainage and systemic antibiotic therapy. PMID- 2233588 TI - [Bowel cleansing prior to colonoscopy. A prospective, randomized, blind comparative study]. AB - A randomized, prospective, single blind study was performed in 90 hospital inpatients to compare the effect of three different bowel preparatory regimens prior to total colonoscopy. The extend of bowel cleansing, acceptance by the patients, side effects as well as body weight, blood pressure, pulse rate and various laboratory parameters served as major assessment criteria. Peroral colonic lavage was superior to a senna preparation and a combined laxative agent with regard to the extend of bowel cleansing (p less than 0.001). The study failed to detect significant differences in terms of acceptance by the patients between the three study groups. Minor deviations were found after the combination laxative (slight decrease of serum potassium levels by 0.32 mmol/l), after the senna preparation (minimal decrease of the heart rate), and after peroral lavage (slightly less weight reduction) as compared with the other study groups, respectively. We conclude that peroral lavage is significantly more effective with regard to the extend of bowel cleansing, when compared with two other bowel preparatory regimens, which use a senna preparation or a laxative combination, respectively. Likewise, this study failed to detect significant differences in terms of acceptance by the patients. PMID- 2233589 TI - [The effect of age and sex on localization, tumor stage and prognosis of colorectal carcinoma]. AB - In a retrospective study including 946 cases with colorectal cancer we analysed age, sex, distribution and stage. There was a significant higher prevalence in women and in all tumor stages women were older than men. The frequencies of Dukes C and proximal colon cancer was significantly higher in women. In older patients we found an increasing incidence of proximal cancer. Instead of tumor stage the age, sex and distribution showed no influence on the outcome. PMID- 2233590 TI - [Imitation of primary sclerosing cholangitis by an infiltrating growing adenocarcinoma originating from the gallbladder]. PMID- 2233592 TI - [Hepatobiliary complications of chronic inflammatory bowel diseases]. PMID- 2233591 TI - [Indications for and efficacy of endoscopic sclerosing treatment of esophageal varices in liver cirrhosis]. PMID- 2233593 TI - [Postgastrectomy syndrome]. PMID- 2233594 TI - [Secondary esophageal perforation following sclerosing of varices--healing with conservative therapy]. PMID- 2233595 TI - [Clinical aspects and therapy of achalasia exemplified by a case of dolicho esophagus]. PMID- 2233596 TI - [Vascular risk factors in patients with ophthalmoplegia]. AB - The occurrence of high-risk factors for vascular disorders was analysed in a group of 43 patients suffering from diplopia of unknown aetiology. The subjects (25 men and 18 women) were aged between 17 and 78 years. Previously excluded were patients with intracranial or orbital tumors, ocular myositis or myasthenia, multiple sclerosis, endocrine orbitopathy, head trauma, cerebral hemorrhage or aneurysms, leucaemic infiltrates or metastasising tumors. Compared to the control groups of extensive epidemiological studies, the patients showed a higher prevalence of arterial hypertension and diabetes mellitus. Adipositas, lipometabolic disturbance and cigarette smoking were also more frequent. The findings support the hypothesis of a vascular origin of eye-muscle paresis. PMID- 2233597 TI - [Serology and culture diagnosis of Campylobacter jejuni infections]. AB - Campylobacter jejuni is known today as one of the most common pathogens in acute infectious enteritis. In 77 patients serological testing by complement fixation as well as stool cultures were performed. A campylobacter jejuni infection was identified in 53% by culture and in 64% by serology, only in 17% the diagnosis was made with both methods. We conclude, that because of these data stool culture and serological testing should be used simultaneously. The complement fixation technique shows an increase in serum titer one to three weeks after beginning of the illness and a decrease in serum titer after four to eight weeks. For this reason it is an appropriate method for the identification of acute infections. PMID- 2233599 TI - [Effect of nitrendipine on the function of the upper gastrointestinal tract]. AB - A double-blind crossover-trial comparing the influence of orally administered nitrendipine and placebo on the function of the upper gastrointestinal tract was carried out in ten healthy volunteers. Esophageal motility, intestinal transit time, size and motility of the gallbladder, serum gastrin levels and gastric secretion (basal and after stimulation with pentagastrin) were determined. No statistically significant differences between nitrendipine and placebo could be observed. Most parameters remained unchanged in both groups. Serum gastrin levels slightly increased after nitrendipine but did not exceed the normal range. The results demonstrate that nitrendipine given in an antihypertensive dosage, in contrast to other calcium antagonists, does not influence the function of the upper gastrointestinal tract. PMID- 2233598 TI - [Therapy of moderate hypertension with the calcium antagonist nitrendipine in combination with beta receptor blocker or diuretic]. AB - The efficacy of the calcium channel blocker nitrendipine alone and in combination with the beta blocking agent acebutolol or hydrochlorothiazide was tested in 34 patients with moderate essential hypertension. After a wash out period of three to four weeks, all patients received placebo for two weeks, thereafter 20 mg of nitrendipine per day for four weeks. When diastolic blood pressure remained above 95 mmHg with nitrendipine, acebutolol (200 mg/d) or the thiazide (25 mg/d) was added in a randomised double-blind fashion. With nitrendipine alone, blood pressure could be normalized in nine patients with a drop in pressure from 168/108 to 152/89 mmHg. The other patients showed a fall in blood pressure from 164/110 to 152/102 mmHg. In these patients, the addition of acebutolol or thiazide was followed by a further fall in blood pressure which was similar with both drugs. With acebutolol blood pressure decreased from 154/102 to 146/94 mmHg and with the thiazide from 152/102 to 147/95 mmHg, respectively. Minor and mostly transient side effects were predominantly seen during therapy with nitrendipine alone. The fall in diastolic but not systolic blood pressure with nitrendipine was correlated with age. The blood pressure lowering effect of nitrendipine was independent of plasma renin activity and intracellular electrolyte concentrations. In the therapy of moderate hypertension, nitrendipine given in combination with a betablocker or a thiazide diuretic is effective and well tolerated. PMID- 2233601 TI - [Therapy of bullous pemphigoid with erythromycin]. AB - Bullous pemphigoid is the most common autoimmune mediated bullous disease in men. Erythromycin combined with a low dose methylprednisolone was tested in eleven patients in a prospective study. A historical collective of the last 33 patients treated before this study was started served as the control group. The duration of hospitalization as an expression of therapeutic response, but also of lowered side effects dropped down from 43 to 33 days in the erythromycin treated group. The study further shows a responder rate of about two thirds of the patients, one third, however, required a high dose regimen of corticosteroids in order to ameliorate. From this could be concluded, that two different subtypes of bullous pemphigoid exist concerning their therapeutic response. PMID- 2233600 TI - [Compliance problems in therapy with levothyroxine]. AB - In order to evaluate problems with long-term levothyroxine therapy, the course of treatment in 185 patients of an endocrinological outpatient ward (88 with euthyroid goiter, 41 with overt or latent hypothyroidism, ten with Hashimoto's thyroiditis, 46 after resection of goiter) was analyzed retrospectively. Duration of therapy ranged from one to 28 years. Suppressive therapy of euthyroid goiter was stopped by the treating physician in eleven patients (11%), in five permanently. To the contrary, 30 patients (34%) stopped medication by themselves 31 times, 29 times, however, levothyroxine was restarted again. Observations in the group with latent hypothyroidism were similar. After operation levothyroxine therapy was stopped by the physician eight times, six times only for a limited time period. Eight patients (17%) decided to stop therapy without knowledge of the treating physician, but in all it was restarted later. The presented results show that the success of levothyroxine therapy of euthyroid goiter as well as of prophylaxis of goiter relapse after operation is threatened by dyscompliance of the patients. In goiter suppression therapy compliance is further challenged by a lack of consequence in therapy planning and guidance. PMID- 2233603 TI - [Radiologic skeletal diagnosis in dialysis patients]. PMID- 2233602 TI - [Syncope in coin lesion of the liver and anemia. Freiburg gastroenterology conference]. PMID- 2233605 TI - [Quality assurance in medicine]. PMID- 2233604 TI - [Prevention of obliterating arterial diseases with acetylsalicylic acid]. PMID- 2233606 TI - [Post-primary multifocal soft tissue and bone tuberculosis]. PMID- 2233607 TI - [Tongue necrosis in temporal arteritis]. PMID- 2233608 TI - [Myelodysplastic syndrome--a retrospective study of 38 patients]. AB - 38 patients diagnosed as myelodysplastic syndrome (MDS) were retrospectively evaluated for clinical course, prognostic factors, diagnostical power of cytology and histology and relevance of hypoplastic myelodysplastic syndrome. Median observation time was 14.5 (0 to 104) months. 15 patients (40%) developed an acute myelogenous leukemia after two to 67 (median eleven) months. Prognosis was negatively influenced by age, suggested myelotoxic agents in prior history and leukemia in first-grade relatives as well as ESR greater than or equal to 30 mm Hg (first hour). FAB-classification and Bournemouth-score reflected prognosis in respect to survival time and development of an acute leukemia. Cytology and histology revealed contradictory results in four of 14 comparable cases (28.6%). Hypoplastic myelodysplastic syndrome was diagnosed by histology in seven out of eight cases. This entity showed significantly lower WBC-values and a considerable longer survival time. PMID- 2233609 TI - [Prevalence, causes and effects of increased iron storage in patients with kidney transplantation]. AB - Patients on chronic hemodialysis often need blood transfusions due to erythropoietin deficiency. Even after successful kidney transplantation iron overload may persist. Former histological studies have revealed siderosis of the liver in 69% of all patients whose serum ferritin was above 1100 ng/ml. The aim of the present study was to evaluate the influence of iron overload on liver function. In 146 symptom free patients with renal allografts serum ferritin was determined to detect possible iron overload. Serum ferritin between 4 and 5480 ng/ml were found (women: 358.7 +/- 105.3; men 282.4 +/- 63.3 ng/ml; x +/- SEM). Twelve patients (8.1%) had ferritin levels higher than 1100 ng/ml. These twelve patients as well as another group of eight patients with renal allografts whose serum ferritin was known to be higher than 1100 ng/ml were included for further evaluation. Their data were matched and compared with those of a control group also patients with renal allograft (same age and sex) whose serum ferritin was lower than 1100 ng/ml. Transaminases (SGPT 22.6 +/- 3.6 vs. 15.4 +/- 6.0 U/l; SGOT 14.7 +/- 2.0 vs. 13.0 +/- 4.8 U/l) and plasma glucose (90.5 +/- 7.1 vs. 76.8 +/- 3.7 mg/dl) were found to be significantly higher (p less than 0.05) in patients with serum ferritin levels above 1100 ng/ml. Elevated transaminases were significantly more frequent in patients with high serum ferritin (9 vs. 2; p less than 0.02) as compared with the control. Ferritin levels significantly correlated with the number of preceding blood transfusions (p less than 0.002). Hbs persistence was detected in six out of 20 patients with high ferritin levels but only in one out of 20 in the control group (p less than 0.05) whereas anti-Hbs prevalence was not different in the two groups. These data indicate that chronic iron overload should be considered as a possible cause of chronic liver disease in patients with renal allografts. PMID- 2233610 TI - [Long-term therapy of tumor pain using morphine-retard tablets]. AB - We analysed the effect of sustained-release morphine tablets in 174 patients with severe cancer pain. A good relief of pain could be obtained in 65% of the patients within the first week and in 80% of the patients at the end of therapy. The mean daily dose was at 178 mg morphine, six patients needed more than 1000 mg per day. The sustained-release morphine was given at fixed intervals, in 80% of the cases every eight hours. No severe side-effects were associated with long term morphine therapy. We often saw nausea and vomiting, constipation and drowsiness, but these side-effects decreased after the first weeks of treatment. Only in ten patients we had to stop therapy because of side-effects. Morphine can be used successfully in the treatment of cancer pain for long periods without concern about tolerance. PMID- 2233611 TI - [Ascites and splenomegaly in childhood. Freiburger gastroenterology discussions]. PMID- 2233612 TI - [Immunocytological phenotyping of leukemias and lymphomas. Methods, results, indications and significance]. PMID- 2233613 TI - [Plasmocytoma: immunology and molecular genetics]. PMID- 2233615 TI - [Immunotherapy of malignant diseases using interleukin 2. Bases, results, trends]. PMID- 2233614 TI - [Immunotoxin: from the idea of "magic bullets" to clinical applications]. PMID- 2233616 TI - [Motivation for and problems in the cooperation of psychosomatic medicine and oncology]. PMID- 2233617 TI - [Therapy and prevention of malaria]. PMID- 2233618 TI - Nicholas M. Greene, M.D. to receive ASA Distinguished Service Award. PMID- 2233619 TI - Ventilation of the newborn with tracheoesophageal fistula. PMID- 2233620 TI - Recolonization of anesthetic instruments after regular treatment with potentially pathogenic organisms. AB - Anesthetic instruments are classified as classes B with regard to sterilization status. This means that washing with soap and water or other detergents is sufficient for reuse. A prospective study was conducted over a 6 month period in the operating (rooms) theatres at Princess Basma Teaching Hospital on anesthetic instruments including laryngoscopes, oxygen masks, airways, tracheal tubes and suction catheters. Fifteen different samples were taken randomly at different sites on these instruments after they had been prepared conventionally for use, and these samples were cultured for bacterial contamination (e.g. P. Aeruginosa). The results showed that potentially pathogenic bacteria were colonizing these instruments. It was concluded that these instruments are important vehicles for transmitting various agents of infection and play an important role in causing nosocomial infections. It is recommended that more effective methods be used for sterilizing these instruments. PMID- 2233621 TI - Cardiopulmonary resuscitation in Saudi Arabia--past, present and future. PMID- 2233622 TI - Influence of head-up versus head-down position on intracardiac pressures during pulmonary artery catheterization. PMID- 2233623 TI - Dysrhythmias during oral surgery--effect of combined local and general anesthesia. AB - In two groups, each of 50 patients undergoing pulpectomy or multiple extractions, effects of combining xylocaine nerve block with halothane general anesthesia were studied. Local blockade of surgical stimuli reduced markedly the incidence of dysrhythmias occurring during halothane anesthesia. Recovery was faster and postoperative analgesia was enhanced. PMID- 2233624 TI - Hypotensive anesthesia for microsurgery of the middle ear--a review. PMID- 2233625 TI - Intraoperative one-lung ventilation for total laryngotracheoesophageal cleft. AB - A case of complete laryngotracheoesophageal cleft, diagnosed as an esophageal atresia with tracheoesophageal fistula, was successfully managed with one-lung ventilation during surgery, although some complications have occurred during surgery. Higher positive end-expiratory pressure (PEEP) was required to produce adequate expansion of the independent lung postoperatively. PMID- 2233626 TI - Droperidol-induced extrapyramidal symptoms in an adolescent following strabismus surgery. PMID- 2233627 TI - Disseminated intravascular coagulopathy diagnosed by computed tomography. AB - A 24-year-old man was brought to casualty after a fall. He suffered from head injury and multiple fractures. On arrival he was apneic and the heart was at a standstill. Resuscitation was successful and the patient was taken to the CT room to assess the extent of his head trauma. At the end of the procedure, maintaining adequate ventilation proved to be very difficult; the blood pressure was rapidly falling and the ECG showed severe bradycardia. Asystole followed and resuscitation was unsuccessful. Postmortem CT scanning of the chest revealed that the tracheobronchial tree was flooded with blood and coagulation profile showed the picture of disseminated intravascular coagulopathy. CT may be useful in the diagnosis of some pathological conditions when autopsy is difficult to perform. PMID- 2233628 TI - Ventricular fibrillation in a normokalemic hemiplegic patient during induction of anesthesia. PMID- 2233629 TI - The use of anencephalic organs: historical and ethical dimensions. AB - The condition of newborn infants with anencephaly, a neural tube defect, is incurable and uniformly fatal. Although physicians reached a consensus two decades ago on the appropriateness of using these infants' organs, ethical and legal questioning has since challenged the grounds on which medical authorities justified transplantation. Advocates have proposed three conceptual strategies to warrant procuring anencephalics' organs: redefining death, excluding the infants from possessing personhood, and intubating and ventilating them while keeping a vigil for brain death. Each of these conceptual schemes has arguable shortcomings in its construction, however; as such, the case for using anencephalic infants as sources of organs has yet to be conclusively demonstrated. PMID- 2233630 TI - Recall strategies and memory for health-care visits. AB - Complex questions in health surveys place heavy cognitive demands on respondents, prompting researchers to appraise how specific cognitive interventions may improve the accuracy of people's answers. Investigators in one experiment asked participants to recall visits to medical providers in forward, backward, or no particular order, and matched results with providers' records. "Free" recall proved marginally superior to forward or backward ordering, although overall respondents underreported the number of visits by 20 percent; participants' gender and self-reported health status, among other factors, also affected quality of recall. The experiment lends support to contentions that the methods of cognitive science applied to survey research better the accuracy of population survey data. PMID- 2233631 TI - Toward new typologies for HMOs. AB - The evolution of health maintenance organizations (HMOs) has entailed changes in both their structural characteristics and incentives to attract physicians' participation. Previous classifications of HMOs have failed to capture explicitly key features of these changes. Two alternative typologies based on incentives or organizational structures may be constructed by examining precise forms of two- or three-tiered contractual arrangements, physicians' payment methods, clienteles served, and means of pooling risks. Classifications of these kinds may represent or aid in generating a valid typology to help managers, consumers, providers, and analysts understand better how HMOs operate and which factors are critical in the dynamic managed-care industry. PMID- 2233632 TI - Estimated prevalence of Alzheimer's disease in the United States. AB - Although awareness of Alzheimer's disease has increased strikingly among professional and lay audiences, precise means do not exist to calculate how many Americans the disease affects. Projecting data from a cohort of 32,000 individuals in a defined community in the United States, however, suggests that there were 2.88 million persons aged 65 or older with probable Alzheimer's disease in 1980. Using U.S. Census Bureau middle series projections yields an estimated total of 10.3 million persons with the disease for the year 2050. Limitations on these estimates notwithstanding, the projections indicate that more studies are needed to identify the etiology of Alzheimer's disease, its incidence, and the future costs of relevant institutional and community care. PMID- 2233634 TI - Informed consent. Opening the doors to physician-patient communication (1). PMID- 2233633 TI - Intracranial aneurysms. A review. AB - Intracranial aneurysms are common, and their rupture carries a grave prognosis. There is no effective way of preventing the development of intracranial aneurysms, but noninvasive means of detection are becoming increasingly practical and, at present, should be used routinely--at least in populations at high risk. SAH is frequently preceded by warning signs that, when recognized by the primary care or the emergency room physician, can lead to prompt and safe surgical intervention. About half the patients who suffer a major rupture either die or remain in poor condition as a result of the hemorrhage. In the rest, surgical intervention has become safer and very effective in preventing subsequent hemorrhage, which occurs in about 50% of patients if the aneurysm is left untreated. Since early surgery should be at least considered in the majority of these patients and since the early treatment of a patient after SAH is so specialized, it appears prudent to manage patients with SAH in units where the necessary neurological and neurosurgical specialized intensive care is available. PMID- 2233635 TI - Beware the UBIT--taxes on qualified plan investments can bite. PMID- 2233636 TI - Promising AIDS drug. PMID- 2233637 TI - AZT-cancer link. PMID- 2233638 TI - Changes in the practice of pathology. PMID- 2233639 TI - Listening to patients and to physicians. PMID- 2233641 TI - Medical charity in the 1990s. PMID- 2233640 TI - Score one for physicians as business people. Minnesota Medicine interviews George V. Tangen, M.D. PMID- 2233642 TI - Cholecystectomy in two small community hospitals. AB - From 1958 to 1988, the author performed 981 cholecystectomies for nonmalignant gallbladder disease in two small southeastern Minnesota hospitals. Of the 981 patients treated, 708 were women. Among patients under age 40, the proportion of women was even higher, about 9 to 1. The peak age for cholecystectomy in both sexes was between 50 and 70. A normal gallbladder was found in 0.5% of patients, and 0.4% had cholecystitis without stones. The complication rate was 9.7%, and the mortality rate was 0.6%. All of those who died were 70 years old or older. These results compare favorably with those published from large institutions and indicate gallbladder surgery can be performed safely and effectively in small hospitals. PMID- 2233644 TI - The National Practitioner Data Bank. From the physician's perspective. PMID- 2233643 TI - The urethral syndrome: myth or reality? A commentary. AB - Although most urologists will agree that dealing with patients suffering from the multiple symptom complex commonly called the urethral syndrome is often time consuming, its origin and treatment continue to generate debate. This essay proposes that entrapment of sensory nerves in the wall of the urethra by fibrosis leads to an abnormal response of Barrington's reflex II, which, in turn, leads to the urethral syndrome. Periurethral fibrosis occurs following trauma, infections, and pelvic irradiation therapy. The urethral syndrome, the author concludes, is therefore based on recognized anatomical factors. The recommended treatment is urethral dilation accompanied by hot sits baths and short courses of Sulfamethoxazole-Trimethoprim. Long-term drug therapy is to be avoided. PMID- 2233645 TI - Successful long-term investing. PMID- 2233646 TI - MMA urges postponement of balance billing cap. PMID- 2233648 TI - Nutrition and immunology: challenge for the 1990s. PMID- 2233647 TI - Proposed modifications to the JCAHO Accreditation Manual For Hospitals by the National Committee for Nutrition Standards. PMID- 2233649 TI - A key to the literature of nutrition and immunology. PMID- 2233650 TI - Part II: Federal involvement in clinical nutrition. PMID- 2233651 TI - Psycho-motor skills in hemiplegic patients: reaction time differences related to hemispheric lesion side. AB - Psychomotor performances are frequently impaired in patients with cerebral lesion. The locus of lesion seems to play an important role: patients with right hemispheric lesion (RHL) frequently show a more important impairment in reaction to external stimuli than patients with left hemispheric lesion (LRH). The aim of this work was to study simple and choice visual reaction times in 2 groups of hemiplegic patients, with different hemispheric lesion side. Results confirm that patients with RHL have significantly more prolonged reaction times. No differences were found in a time we called choice time, related to "central delay" confirming that the more important psychomotor performances deficit in RHL patients is mainly related to impairment of attention, alertness, arousal systems. PMID- 2233652 TI - [Prolonged confusion syndrome in the course of cyclosporine treatment: a state of confusion?]. AB - Cyclosporine is a potent immunosuppressant that is more and more widely used, particularly after organ transplantations. Many neurological side effects, including convulsions, that could be related to this drug, have been previously observed, most often with high blood concentrations. We report, for the first time, a case of prolonged confusion where a non convulsive status epilepticus may be discussed. It occurred in a 64-year-old woman, 17 days after a liver transplantation. The whole blood cyclosporine value was 230 micrograms/l (normal range: 100-200 micrograms/l) at the beginning of the status epilepticus. The cyclosporine imputability and the part of other factors that could have facilite are discussed. PMID- 2233653 TI - Nocturnal paroxysmal dystonia with atypical short-lasting attacks. PMID- 2233654 TI - [Clinico-pathological study of xanthogranulomatous cholecystitis]. AB - Xanthogranulomatous cholecystitis (XGC) is an uncommon lesion which may form a tumor-like mass in inflamed gallbladders. In a review of 44 cases there were 40 associated with gallstones which had been incarcerated in the neck of the gallbladder, 10 with past histories of abdominal surgeries, 15 with diabetes mellitus, three with carcinomas in the neck of the gallbladder and four with carcinomas in the other organs. Radiologically the differential diagnosis of gallbladder cancer and XGC was difficult in several cases. Thirty five cases of XGC have been diagnosed as chronic cholecystitis and 7 have been mistaken for feature of XGC in the contrast enhancement CT that is, detection of an intramural low density mass with continuously enhanced internal membraneous layer of the gallbladder wall. In view of the clinico-pathological findings of XGC, the lesions appear to result from intramural extravasation of bile and subsequent xanthogranulomatous reaction under obstructive conditions in the neck of the gallbladder. We conclude that XGC is not an uncommon special type of cholecystitis but an accompanied lesion sometimes seen in a kind of cholecystitis. PMID- 2233655 TI - [A clinical study of cerebral perfusion during pulsatile and nonpulsatile cardiopulmonary bypass]. AB - The purpose of this study was to determine the effect of pulsatile flow on cerebral perfusion under cardiopulmonary bypass (CPB). Twenty-three patients who underwent cardiac operations were divided into two comparable groups: Group A (N = 11) had standard nonpulsatile flow, while in Group B (N = 12), a pulsatile pump was used. The blood flow of left common carotid artery and radial arterial pressure were continuously monitored during cardiac operation in both groups and cerebral vascular resistance was calculated. In Group B, the perfusion pressure of left common carotid artery was monitored and compared with that of radial artery. Arterial and internal jugular venous blood were sampled and the difference of cerebral A.V O2 contents and cerebral oxygen consumption was calculated. Cerebral vascular resistance in Group B (54.0 +/- 11.2% of the value of before-CPB) significantly decreased compared to that in Group A (72.2 +/- 11%) at the end of CPB (p less than 0.05). Pulse pressure following pulsatile CPB flow was 15.1 +/- 5.8 mmHg monitored in radial artery and it reduced to 8.5 +/- 5 mmHg in left common carotid artery. Although there was no significant difference in cerebral oxygen consumption of both groups during and just after CPB, the difference of cerebral A-V O2 contents of Group B was greater than Group A just after CPB. These data suggest that pulsatile flow may minimize the cerebral microcirculatory shunt during CPB, resulting from the reduction of cerebral vascular resistance. PMID- 2233656 TI - [The effect of peripheral blood leukocyte depletion on reperfusion injury of warm ischemic lung]. AB - To clarify the role of leukocytes in reperfusion injury of preserved lung for lung transplantation, leukocyte depletion was performed and lung tissue generation of oxygen metabolites and histological evaluation were investigated. METHOD: 12 mongrel dogs were utilized, divided into 2 groups. In group A, hilar stripped left lung was submitted to 2 hour warm ischemia and 2 hour reperfusion. Blood filtration was performed three times using leukocyte filter. In group B, warm ischemia and reperfusion were performed without filtration. Lipid peroxidation products of lung tissue were measured by thiobarbituric acid assay. Tissue damage was estimated by wet/dry ratio and histological analysis. Results 1). Peripheral blood counts revealed that effective leukocyte depletion was obtained and leukocyte efflux from reperfused lung was observed in group A. 2) Significant increase of lung tissue oxygen metabolite generation after reperfusion was observed in group B, while no significant fluctuate of tissue MDA titers was noted in group A. Tissue damage estimated by histological analysis and wet/dry ratio were considered to be controlled in group A compared with group B. In conclusion, leukocyte depletion by in vivo use of leukocyte filter was effective for reperfusion injury of warm ischemic lung and oxygen metabolites may play a role in these process. PMID- 2233657 TI - [An experimental study of the influence of positive end-expiratory pressure for a bidirectional cavopulmonary shunt]. AB - In 8 mongrel dogs (weight 9-13 kg), we created a bidirectional cavopulmonary shunt through 4th intercostal thoracotomy. Positive end-expiratory pressure (PEEP) was added from 0cmH2O to 16cmH2O at the steps of 2cmH2O. The heart rate (HR), central venous pressure (CVP), pulmonary artery pressure (PAP), femoral artery pressure (FAP), pulmonary vascular resistance index (PVRI), and systemic vascular resistance index (SVRI) were measured as parameters of hemodynamics. Cardiac output (CO), pulmonary artery flow at proximal and distal site of this shunt (D-SF, P-SF) were measured using a magnetic flow meter. Blood gas analysis (PH, PaO2, PaCO2, HCO3-) were performed at the same time. HR had no significant change. CVP, PAP, PVRI, SVRI increased significantly (p less than 0.05, p less than 0.05, p less than 0.05, p less than 0.05) at 2cmH2O (9.2 +/- 2.5 mmHg), 10cmH2O), (29.3 +/- 5.5 mmHg), 4cmH2O (287 +2- 56 dyne.sec.cm-5.m2), and 8cmH2O (1298 +/- 156 dyne.sec.cm-5.m2) compared with 0cmH2O (87.3 +/- 2.6 mmHg, 26.8 +/- 3.4 mmHg, 240 +/- 29 dyne.sec.cm-5.m2, 1136 +/- 176 dyne.sec.cm-5.m2). FAP, CO, D SF, P-SF decreased significantly (p less than 0.01, p less than 0.05, p less than 0.01, p less than 0.05) at 6cmH2O (129 +/- 7 mmHg), 2cmH2O(0.44 +/- 0.05 L/min), 2cmH2O(449 +/- 47 ml/min), and 8cmH2O(105 +/- 17 ml/min) compared with 0cmH2O(148 +/- 11 mmHg, 048 +/- 0.06 L/min, 471 +/- 44 ml/min, 132 +/- 19 ml/min). On blood gas analysis, PaO2 increased significantly (p less than 0.05) from 2cmH2O PEEP except PH, PaCO2, HCO3-. A mechanism for decline in D-SF was considered of being a secondary effect due to increase in CVP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233658 TI - [A case of fatal graft-versus-host disease following blood transfusion in esophageal cancer documented by homozygous changes of HLA typing]. AB - A 72 year-old Japanese male with esophageal cancer underwent esophagectomy. After seemingly uneventful recovery, he developed high fever on 11 post-operative day (POD), rashes over the whole body on 13 POD and leukopenia on 15 POD. On 22 POD, thrombopenia and parenchymal bleeding of lungs were noted. He died on 26 POD after progressive hypoxia and hypotension. HLA type of peripheral lymphocytes on him changed homozygously to that of the transfused fresh blood. Skin biopsy showed mild leukocyte infiltration in the epidermis and the dyskeratotic keratinocytes were associated with a contiguous lymphocyte, the so-called satellite cell necrosis. In the findings of autopsy, aplastic bone marrow and atrophied spleen, whose weight was 14g, were noted. Based on the clinical picture, skin biopsy and HLA study findings, we diagnosed this case as post transfusion GVHD. We think that high age, operative injury and preoperative irradiation might be inducement to reveal post-transfusion GVHD in this case. PMID- 2233659 TI - [A clinical case of ABO-incompatible living renal transplantation]. AB - We successfully made ABO-incompatible renal transplantation, of which report is methodologically the first in Japan and probably the second in the world to our knowledge. Sixty year-old-female (mother) with B-blood type donated her right kidney to 36 years-old male (son) with O-blood type. Pretransplant removal of plasma isoagglutinin of the recipient through plasma exchange with albumin solution followed by hemodialysis with administration of fresh frozen B-type plasma effectively reduced the anti-BIgM-antibody titre of x256 to x8 and the anti-IgG-antibody titre of x512 to x16. Splenectomy was performed at the time of transplantation. On the 10th POD, the anti-B antibody titres were more decreased to IgM antibody x2 and IgG antibody x8. Patient is doing well without any sign of rejection as of 4 months postoperatively. PMID- 2233660 TI - [Human erythrocyte polyamine levels after partial hepatectomy: preliminary report]. PMID- 2233661 TI - [Effect of tamoxifen on estrogen-stimulated growth of MCF-7 tumors in athymic mice: preliminary report]. PMID- 2233662 TI - [Evaluation of in vitro prostaglandin production in human peripheral macrophage derived from healthy subjects and patients with cancer: preliminary report]. PMID- 2233663 TI - [Intravenous administration of vancomycin for postoperative MRSA infection and its pharmacokinetics: preliminary report]. PMID- 2233664 TI - [Intramural pH monitoring: early diagnosis of intestinal ischemia: preliminary report]. PMID- 2233665 TI - [Meaning in measurement of bone mineral content as preoperative evaluation of aged patients]. AB - Recently, mean span of life has been prolonged, and extensive operations are performed on aged patients. However, there are cases which have a difference between their chronological and actual ages. Bone mineral content (BMC) decreases with age and the decrease in BMC might suggest deterioration of immunological competence as observed in osteoporosis. Whether BMC can be an index for evaluation of geriatric patients' actual age from the aspect of immunological competence was investigated. Subjects were 54 cases aged more than 60. Twenty-one healthy young males and females were enrolled as the control group. Quantitative CT is used for assessment of BMC. The value obtained by dividing BMC by the standard BMC of the same age and sex, was defined as BMC index. BMC indices of normal BMC group were more than 0.8 and those of decreased BMC group were less than 0.8. Some immunological markers were investigated. Lymphocyte subset OKT3+ was reduced and juvenile lymphocytes expressed by OKT6+ and OKT3+-(OKT4+ + OKT8+) increased (corrected). Increased in juvenile lymphocyte and decrease in lymphocyte blast transformation and competence of generating interleukin 2 were observed in decreased BMC group. BMC is useful as preoperative evaluation for geriatric operative cases and patients of BMC index below 0.8 need to be paid attention to postoperative infection. PMID- 2233666 TI - [Effect of postoperative hypertonic sodium infusion in the patients with total gastrectomy for gastric cancer]. AB - In 17 patients with gastric cancer undergoing total gastrectomy, the effect of postoperative hypertonic sodium infusion were studied. The subjects were divided into 2 groups by concentration in the postoperative infusions. Group 1(Na group): over 5.0 mEq/Kg/day of sodium were infused in the postoperative days (POD). (End of operation to POD-4), Group 2 (Control group): 2.0-2.5 mEq/Kg/day of sodium (End of Op. to POD-1), 1.5-2.0 mEq/Kg/day (POD-2-4). 2.0-2.5 mEq/Kg/day were infused after POD-5 in both groups. In the Na group, NAG-Index, FENa and BUN were higher than those of control group. And cumulative primary Na balance (from end of operation to POD-5) indicated positive balance in Na group, and negative in control group. Furthermore, the cumulative infused sodium dose correlated with cumulated urinary sodium dose, potassium dose and cumulative NAG dose (from end of operation to POD-5). Significant difference was observed between two groups in urinary nitrogen. These findings suggest that the sodium dose in the postoperative infusion were suitable with 2.0-2.5 mEq/Kg/day. PMID- 2233667 TI - [Selective conservatism in the management of abdominal stab wounds]. AB - Two hundred and two consecutive patients with abdominal stab wounds in a 14-year period were analysed as follows: (1) The patients were classified into 4 categories; type I (no peritoneal penetration) 12%, type IIa (peritoneal penetration, no organ injury) plus type IIb (organ injury, no repair required) 26% and type III (organ injury, repair required) 62%. Injuries caused by kitchen knife or violence, wounds in the lower chest or epigastrium, and harakiri injuries (Japanese traditional method of suicide) resulted in high frequencies of type III injury. (2) Hematoemesis, hematuria, unstable hemodynamics, and signs of peritonitis were reliable indications for immediate laparotomy. Both stabography and diagnostic peritoneal lavage were unuseful as adjunctive diagnostic methods. (3) A policy of selective management in 126 patients (1981-1988), comparing with a policy of mandatory exploration in 76 patients (1975-1980), reduced unnecessary laparotomy rate from 32% to 14% (p less than 0.01). (4) Injury patterns, observed in this series and the reported series from Japanese emergency centers, were strikingly different from the American series. The author emphasize the threat of morbidity caused by delayed diagnosis in the application of selective conservatism and propose the acceptable rate of unnecessary laparotomy; less than 15%. PMID- 2233668 TI - [Characterization of a liver metastatic cell line derived from a human gastric cancer cell line]. AB - This study was carried out to investigate whether there is any difference of biological characteristics between a gastric cancer cell line (KATOIII) and another cell line derived from liver metastasis of the same cell line (KATOIII H2). The liver metastasis was produced by intrasplenic injection of the fluid containing of KATOIII in nude mouse and new cell line was established using the cells of metastatic site. The results are as follows. 1) Inoculation of KATOIII H2 into the spleen produced liver metastases in all of the experimental animals, whereas the same procedure with KATOIII produced metastasis only in 30% of the animals. 2) KATOIII-H2 exhibited more prominent platelet-aggregating activity than KATOIII. 3) There is no difference between two cell lines on doubling time, histological findings of the xenografts and chromosomal number. 4) DNA index of KATOIII-H2 is lower than KATOIII and the trisomy in NO. 20 chromosome of KATOIII H2 was noted. The results indicate that metastatic potential is different between two cell lines and this fact is probably in a part because of the different platelet-aggregating activity of each cell line. PMID- 2233669 TI - [Serorrhaphy prevents regeneration of vagus nerve fibers after proximal gastric vagotomy]. AB - Spouting or regeneration of vagus fibers occurs after vagotomy. An axonal tracing method was used to see the long-term effect of serorrhaphy in the prevention of axonal regeneration after proximal gastric vagotomy (PGV) in ferrets. METHODS: A neurotracer, wheat-germ agglutinin-horseradish peroxidase (0.5 mg), was injected subserosally at the corpus of the anterior stomach (1) without PGV (n = 4), (2) immediately after PGV (n = 2), (3) one year after PGV with serorrhaphy (n = 3), and (4) one year after PGV without serorrhaphy (n = 3). The ferrets were killed by perfusion-fixation. The brainstem was processed histochemically. Numbers of labeled cells in the dorsal motor nucleus of the vagus were statistically analyzed using square-root transformation. RESULTS: Numbers of labeled cells were 348 for (1), 13 for (2), 2 for (3), and 43 for (4). Multiple comparisons revealed significant differences in (1) vs. (2), (3), (4) and (3) vs. (4). DISCUSSION: The number of preganglionic efferent vagus cells decreased acutely after PGV, which persisted one year. Regenerated vagus axons were less in the chronic group with serorrhaphy than in the group without one. Thus time factor did not influence the regeneration, but serorrhaphy was important in preventing vagal regeneration. CONCLUSION: Serorrhaphy during PGV prevents the regeneration of preganglionic efferent vagus fibers. PMID- 2233670 TI - [Preoperative oral antimicrobial bowel preparations in elective colorectal surgery]. AB - Colorectal surgery is associated with high incidence of postoperative wound infection due to contamination of the field of operation by organisms from the intestine. A consecutive series of 300 patients undergoing elective operations on the colon and rectum, was studied to determine the efficacy of oral antibacterial preparations on the influence of intestinal organisms at operation and the incidence of postoperative wound infection. The patients were divided into four groups as their preoperative bowel preparations as follows; 1st group: mechanical preparation alone, 2nd group: mechanical preparation and oral kanamycin, 3rd group: mechanical preparation and oral kanamycin and metronidazole, and 4th group: mechanical preparation and oral polymyxin B and metronidazole. The results of bacteriological studies on specimens taken by swab from colonic lumen and wound at operation showed effectiveness of kanamycin and polymyxin B against aerobic gram-negative rods and metronidazole against anaerobes. The rates of postoperative wound infection were 47.5% in 1st group, 27% in 2nd group, 12% 3rd group, and 2.7% in 4th group, respectively. PMID- 2233671 TI - [Clinical significance of DNA content of rectal cancer measured by flow cytometory]. AB - DNA content of 369 rectal cancers was measured by flow cytometry. One hundred and four (28.2%) were diploid, 252 (68.3%) were aneuploid and 13 (3.5%) were tetraploid. Diploid cancers were associated with an improved 5 year survival (p less than 0.001) and were more likely to be diagnosed at an early stage. However DNA content did not confer independent prognostic information in a Cox model based on four discrete pathological variables. Patients were classified by a new system of prognostic grouping and those with a very good or a very poor outlook were removed leaving 137 prognostic group 3 patients. No further substratification of this group by DNA content or by four additional pathological variables could be achieved. As the new prognostic system is not improved by the additional of ploidy, routine adoption of flow cytometry in the assessment of rectal cancer can not be recommended. PMID- 2233672 TI - [Evaluation of correlation between the disappearance rate of indocyanine green and the maximum removal rate]. AB - The disappearance rate of indocyanine green (K.ICG) and the maximum removal rate (Rmax) usually correlate with each other. However, in some cases it was shown there was a dissociation between them. We investigated the relationship between the two rates in 146 subjects. K.ICG and Rmax correlated strongly with a correlation coefficient of 0.749 (p less than 0.001). Sixty-six cases were included in the limits of 95% confidence, and the other 80 cases outside the limits were defined as dissociated cases. Among them a lower Rmax rate as compared to the K.ICG rate was found in many cases of obstructive jaundice. Particularly a lower K.ICG rate compared to the Rmax rate was found in many cases of liver cirrhosis accompanied by esophageal varices and idiopathic portal hypertension. On the other hands, we performed multiple regression analysis on 12 other liver function tests. K.ICG was strongly related to platelet count, circulatory blood volume, and albumin, all factors relating to portal hypertension. Rmax largely depended on LCAT, A/G ratio, and cholinesterase, which are Therefore, the dissociation between K.ICG and Rmax was caused by differences in the characteristic of each disease. PMID- 2233673 TI - Nitrate reductases of Escherichia coli: sequence of the second nitrate reductase and comparison with that encoded by the narGHJI operon. AB - The structural genes for NRZ, the second nitrate reductase of Escherichia coli, have been sequenced. They are organized in a transcription unit, narZYWV, encoding four subunits, NarZ, NarY, NarW and NarV. The transcription unit is homologous (73% identity) to the narGHJI operon which encodes the genes for NRA, the better characterized nitrate reductase of this organism. The level of homology between the corresponding polypeptides ranges from 69% for the NarW/NarJ pair to 86% for the NarV/NarI pair. The NarZ polypeptide contains the five conserved regions present in all other known molybdoproteins of E. coli and their relative order is the same. The NarY polypeptide, which contains the same four cysteine clusters in the same order as NarH, is probably an electron transfer unit of the complex. Upstream of narZ, an open reading frame, ORFA, is present which could encode a product which has homology (73% identity) with the COOH terminal end of NarK. The ORFA-narZ intergenic region, however, is about 80 nucleotides long and does not contain the cis-acting elements, NarL and Fnr boxes, nor the terC4 terminator sequence present in the 500 nucleotide narK-narG intergenic region. This might explain why the narZYWV and the narGHJI operons are regulated differently. Our results tend to support the hypothesis that a DNA fragment larger than that encompassing the narGHJI genes has been duplicated. PMID- 2233674 TI - Paternal inheritance of mitochondria in rapeseed (Brassica napus). AB - Transfer of a mitochondrially associated plasmid following sexual crosses in Brassica napus rapeseed suggested that paternal mitochondria were being transferred to the cytoplasm of the egg. To examine this possibility further, plants carrying the chloroplast (cp) marker of triazine resistance, but which had lost the plasmid associated with the mitochondria of this cytoplasm, were crossed as females to males carrying the polima cytoplasm. The males carried a nuclear fertility restorer gene on an extra chromosome to overcome the male sterility marker conferred by the mitochondria of this cytoplasm. Approximately 10% of the F1 progeny displayed the male sterility and flower morphology of the male parent. Mitochondrial (mt) DNA from the progeny showed the combined restriction patterns of both parents, but this mt heterogeneity did not continue into subsequent generations. All progeny retained the cp DNA restriction patterns of the maternal plant as well as resistance to the herbicide atrazine. To date, sexually mediated cybrid plants have shown no morphological abnormalities and have maintained their unique combination of cp and mt traits through several sexual generations. PMID- 2233675 TI - Use of oligonucleotide probes to identify members of two-component regulatory systems in Xanthomonas campestris pathovar campestris. AB - Two-component regulatory systems comprising a sensor and a regulator protein, both with highly conserved amino acid domains, and commonly genetically linked, have been described in a range of bacterial species and are involved in sensing environmental stimuli. We used two oligonucleotide probes matching the postulated coding regions for domains of sensor and regulator proteins respectively in Xanthomonas campestris pathovar campestris (Xcc) to identify possible two component regulatory systems in Xcc. Two different fragments of Xcc DNA with homology to both of these probes were cloned. The DNA sequence of part of one of these fragments encompassed a potential open reading frame (ORF), the predicted amino acid sequence of which had extensive homology with regulator proteins of two-component regulatory systems. Analysis of the predicted amino acid sequence for the 3' end of an adjacent ORF revealed a very high level of homology with the C-terminal end of sensor proteins. Strains of Xcc with Tn5-induced mutations in the regulator gene were affected in extracellular polysaccharide production, and also in resistance to salt and chloramphenicol. No effects of mutation in the second clone were observed. PMID- 2233676 TI - T-T cyclobutane dimers are misinstructive, rather than non-instructive, mutagenic lesions. AB - The lesions produced by SOS-dependent mutagens in Escherichia coli are commonly referred to as nonpairing or non-instructive. Although these terms are likely to be appropriate for some lesions, particularly the abasic site, for others, such as the cyclobutane dimer, their suitability is open to question. To address this question, we have compared the error frequencies and spectra that result when a uniquely located T-T sequence, carried in a single-stranded vector, contains either a cis-syn or a trans-syn cyclobutane dimer, or when either the 5'T or 3'T is converted to an abasic site. The data suggest that the high accuracy with which the dimer-containing templates are replicated is unlikely to be the consequence of polymerase preference for the non-instructive insertion of dAMP. Similarly, mispairing, rather than non-pairing, is likely to cause mutations. Cyclobutane dimers seem therefore to be misinstructive rather than non instructive lesions, and the common feature shared by SOS-inducing lesions is more their ability to block replication than inability to form correct base pairs. PMID- 2233677 TI - Interchromosomal and intrachromosomal recombination in rad 18 mutants of Saccharomyces cerevisiae. AB - The frequency of intra- and interchromosomal recombination was determined in RAD18 and rad18 deletion and rad18-3 mutant strains. It was found that spontaneous interchromosomal recombination at trp5, his1, ade2, and MAT was elevated 10- to 70-fold in the rad18-3 and rad18 delta mutants as compared to the RAD+ strains. On the other hand the frequencies of spontaneous intrachromosomal recombination for the his3 delta 3', his3 delta 5' and the his4C-, his4A- duplications and for heterothallic mating type switching were only marginally elevated in the rad18 deletion mutant, and recombination between ribosomal DNA repeats was only 2-fold elevated in the rad18-3 mutant. These differences may be due to a haploid versus diploid specific difference. However interchromosomal recombination was elevated 40-fold and intrachromosomal recombination was only marginally (1.5-fold) elevated in a diploid homozygous for rad18 delta, arguing against a haploid versus diploid specific difference. Possible explanations for the difference in the elevated levels of intra- versus interchromosomal spontaneous recombination are discussed. PMID- 2233678 TI - Cellular localization of the MalG protein from the maltose transport system in Escherichia coli K12. AB - In Escherichia coli five proteins are directly involved in the high affinity transport system for maltose and maltodextrins. Sequence data and genetic evidence indicate that three of them, MalF, MalG and MalK, are associated with the inner membrane. In order to characterize the MalG protein more thoroughly and to determine its subcellular localization under physiological conditions, we generated well-defined mutations induced in vitro that affect the size and the function of the malG gene product. Wild-type and mutant proteins were detected in total bacterial extracts and on purified subcellular fractions with the help of an antibody prepared against a synthetic peptide based on the predicted N terminal sequence of MalG. The protein was solubilized from crude membranes by the detergent Triton X-100, indicating that it was localized in the inner membrane. A mutant carrying an in-phase insertion of four amino acids into a region conserved in several inner membrane proteins from periplasmic transport systems displayed a maltose-negative phenotype. This suggested that this region is very probably essential for MalG function. PMID- 2233679 TI - Colicin M is only bactericidal when provided from outside the cell. AB - The colicin M structural gene, cma, was subcloned in a vector which allowed temperature-inducible control of its expression. Induction of expression of cma in colicin M uptake proficient strains was lethal for the host cell when the colicin M immunity protein was not present. In liquid culture cells lysed, and no colonies were formed on solid media. These effects were not observed in mutants defective in the colicin receptor (FhuA) or uptake functions (TonB, TolM), nor in wild-type cells treated with trypsin prior to induction of cma expression. It was concluded that cytoplasmic colicin M is not toxic for the producing cell. To exert a lethal effect the colicin has to enter the cell from outside. Cells expressing cma released small amounts of colicin M. PMID- 2233680 TI - Developmentally regulated expression of a sunflower 11S seed protein gene in transgenic tobacco. AB - Helianthinin is the major 11S seed storage protein of sunflower (Helianthus annuus). Like most seed proteins, helianthinin is encoded by a small gene family; two members of this gene family, HaG3-A and HaG3-D, have been isolated and characterized. Tobacco was transformed with a 6 kb fragment of HaG3-A containing the helianthinin coding region flanked by 3.8 kb upstream and 0.4 kb downstream sequence. Expression of helianthinin was developmentally regulated in seeds of transgenic tobacco plants; furthermore, helianthinin polypeptides were proteolytically processed and targeted to the protein bodies of transgenic tobacco. A fragment of HaG3-A from -2376 to +24 was fused to the beta glucuronidase (GUS) reporter gene and transferred to tobacco. GUS expression driven by this helianthinin upstream region was developmentally regulated in seeds. Germinating seedlings of the same transformant exhibited a time-dependent decrease in GUS activity with none detected by 6 days post imbibition (DPI). Histochemical analysis of GUS activity in embryos and 2 to 5 DPI seedlings showed expression restricted to the cotyledons and upper embryonic axis with none detected at the radicle end. No GUS activity was found in cotyledons, hypocotyls, leaves, and roots of 18 day seedlings or in leaves of an 8 week F1 plant. These results indicate that the cis-regulatory elements required for developmental control of the HaG3-A helianthinin gene are located in a 2.4 kb upstream region of this gene. This region was sequenced together with the upstream region of the HaG3-D helianthinin gene. PMID- 2233681 TI - A repeated chromosomal DNA sequence is amplified as a circular extrachromosomal molecule in rice (Oryza sativa L.). AB - The plasmid pE10 is a pBR322-derived plasmid carrying a 4.5 kb rice (Oryza sativa L.) repeated DNA sequence. The cloned sequence has been shown to be amplified in cultured rice cells. The analysis of practically intact chromosomal rice DNA molecules by pulsed field gel electrophoresis has now shown that the amplification is associated with the appearance of extrachromosomal molecules. In fact, pE10 hybridizes exclusively with unfractionated DNA from leaf protoplasts, while it recognizes predominantly an extrachromosomal DNA molecule (ECD) of about 45 kb and its multiples in the case of protoplasts from cultured cells. Insensitivity to the action of the exonuclease Bal31 suggests that the molecule is circular. Analysis of restriction endonuclease products with both standard horizontal and pulsed field gel electrophoresis suggest that the extrachromosomal DNA, and its chromosomal counterpart, is composed of tandemly repeated units of about 7 kb. Thus, the smaller extrachromosomal circle should contain 6-7 repeats, while the sequence cloned in pE10 is a subset of this repeat. The extrachromosomal DNA represents about 1% of total rice DNA and its level of amplification is not affected by the different phases of growth in culture. PMID- 2233682 TI - Par site of the ColN plasmid: structural and functional organization. AB - A par site involved in the resolution of multimeric plasmid DNA forms was localized in a 679 bp SalI-KpnI fragment of the small colicinogenic plasmid ColN. It was shown that replication of the monomeric pUC19 recombinant plasmid carrying the par region of ColN does not result in the formation of significant numbers of multimers. In order to function properly, the ColN multimer resolution mechanism requires the product of the xerA gene, just as in the case of ColE1. Nucleotide sequence analysis of the par region of ColN revealed substantial homology with the par locus of the ColE1 plasmid. The results of this study and data from the literature indicate that the par sites of ColE1-type plasmids have substantial homology and the same mechanism of action, and in fact represent a universal stability module for small multicopy colicinogenic plasmids. PMID- 2233683 TI - Either of two nod gene loci can complement the nodulation defect of a nod deletion mutant of Rhizobium leguminosarum bv viciae. AB - A deletion mutant of Rhizobium leguminosarum biovar viciae lacking the host specific nodulation (nod) gene region (nodFEL nodMNT and nodO) but retaining the other nod genes (nodD nodABCIJ) was unable to nodulate peas or Vicia hirsuta, although it did induce root hair deformation. The mutant appeared to be blocked in its ability to induce infection threads and could be rescued for nodulation of V. hirsuta in mixed inoculation experiments with an exopolysaccharide deficient mutant (which is also Nod-). The nodulation deficiency of the deletion mutant strain could be partially restored by plasmids carrying the nodFE, nodFEL or nodFELMNT genes but not by nodLMN. Surprisingly, the mutant strain could also be complemented with a plasmid that did not carry any of the nodFELMNT genes but which did carry the nodO gene on a 30 kb cloned region of DNA. Using appropriate mutations it was established that nodO is essential for nodulation in the absence of nodFE. Thus, either of two independent nod gene regions can complement the deletion mutant for nodulation of V. hirsuta. Similar observations were made for pea nodulation except that nodL was required in addition to nodO for nodulation in the absence of the nodFE genes. These observations show that nodulation can occur via either of two pathways encoded by non-homologous genes. PMID- 2233685 TI - Identification and characterization of stamen- and tapetum-specific genes from tomato. AB - Differential screening of a tomato cDNA library produced from pre-anthesis stamens resulted in the isolation of 25 cDNA clones that hybridized to probes made from stamen RNA and showed no hybridization to probes made from RNA of vegetative organs. The 25 clones were found to represent 11 noncross-hybridizing classes. The majority of these clones were derived from genes that were single or low copy in the tomato genome. Northern RNA blotting experiments of vegetative and floral organs at several stages of development demonstrated that expression in all 11 classes was confined to floral organs. Of the 11 classes 9 were found to be expressed exclusively in stamens prior to anthesis. Two classes showed expression in immature stamens and in petals, with one of these two additionally being expressed in mature stamens at anthesis. Clones from three of the classes that were expressed exclusively in stamens were used as probes for in situ localization of RNA in floral organs. These experiments demonstrated that expression of the genes corresponding to these clones was confined to the tapetal cells of the anthers. Expression of one of the three genes was found to be limited to a single cell type during the 5-6 day period from late meiosis to immature pollen formation. PMID- 2233686 TI - Differentiated induction of cytochrome P450b/e and P450p mRNAs by dose of phenobarbital in primary cultures of adult rat hepatocytes. AB - Phenobarbital induces cytochromes P450 (P450s) of not only the class IIB gene subfamily (i.e., P450b and P450e) but also the class IIIA gene subfamily (P450p and P450pcn2). To determine whether coinduction of these structurally dissimilar gene products involves the same mechanism, we examined the dose dependency of phenobarbital induction of the mRNAs for these four P450s in a new responsive system for primary monolayer cultures of adult rat hepatocytes on Matrigel, a reconstituted basement membrane. Two-day treatments of the cultures with phenobarbital produced marked dose-dependent increases in the levels of P450b, P450e, and P450p mRNAs, which reached maximal inductions ranging from 11- to greater than 193-fold. Although the dose-response relationships for the inductions of P450b and P450e mRNAs by phenobarbital were similar (ED50 = 1.5 x 10(-5) and 5.7 x 10(-6) M, respectively), the dose-response curve for the induction of P450p mRNA was positioned distinctly to the right (ED50 = 3.0 x 10( 4) M). This difference reflects a potency ratio of 20-fold for P450p/P450b mRNA induction. Phenobarbital also produced a weak dose-dependent induction of P450pcn2 mRNA, with a potency (ED50 = 3.4 x 10(-5) M) intermediate between those for P450b/e and P450p. In a similar experiment using two phenobarbital-like inducers, (trans)nonachlor and clotrimazole, the relative inductions of P450b, P450e, P450p, and P450pcn2 mRNAs proved to be similar to those produced by phenobarbital (P450p/P450b potency ratios = 14- and 16-fold, respectively). These findings provide strong further evidence in support of the newly emerging concept that "phenobarbital" induction of the responsive class IIB and class IIIA P450 isozymes likely reflects multiple mechanisms. PMID- 2233684 TI - Differential regulation of STA genes of Saccharomyces cerevisiae. AB - The single glucoamylase gene (SGA1) of the yeast Saccharomyces cerevisiae is expressed exclusively during the sporulation phase of the life cycle. Enzymatic studies and nucleic acid sequence comparisons have shown that the SGA1 glucoamylase is closely related to the secreted enzymes of S. cerevisiae var. diastaticus. The latter are encoded by any of three unlinked STA genes, which have been proposed to derive from the ancestral SGA1 form by genomic rearrangement. We show that the regulation of SGA1 is distinct from that of the other members of the STA gene family. SGA1 expression did not respond to STA10, the primary determinant of glucoamylase expression from STA2. Unlike STA2, SGA1 was not regulated directly by the mating type locus. Expression of SGA1 depended on the function of the MAT products in supporting sporulation and not on the formation of haploid progeny spores or on the composition of the mating type locus per se. We conclude that the STA genes acquired regulation by STA10 and MAT by the genomic rearrangements that led to their formation. This regulation is thus distinct from that of the ancestral SGA1 gene. PMID- 2233687 TI - Perturbations of intracellular calcium distribution in kidney cells by nephrotoxic haloalkenyl cysteine S-conjugates. AB - The Ca2(+)-sensitive dye fura-2 was used to investigate the disturbances in intracellular Ca2+ concentration [( Ca2+]i) and distribution induced by the nephrotoxic cysteine S-conjugate S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and its homocysteine analog S-(1,2-dichlorovinyl)-L-homocysteine (DCVHC) in LLC-PK1 cells. After 24-hr treatment with DCVC, the average [Ca2+]i increased from 88 +/- 23 nM to 415 +/- 92 nM. Digital image analysis revealed that the mitochondrial region, which was stained with rhodamine-123, contained lower Ca2+ concentration ([Ca2+]) than other cell areas. This distribution was different from the higher [Ca2+] in the nuclear and mitochondrial regions observed in control cells. In DCVHC-treated cells, there was also an increase in [Ca2+]i to 355 +/- 85 nM, but the increase in [Ca2+] was greater in the mitochondrial region, compared with the rest of the cell. After 72-hr treatment with DCVC or DCVHC, the average [Ca2+]i was 410 +/- 85 nM and 340 +/- 90 nM, respectively, and blebs with markedly higher [Ca2+] (600-1000 nM) than the rest of the cell appeared in both DCVC- and DCVHC treated cells. Moreover, in DCVC-treated cells the mitochondria could not be stained with rhodamine-123, indicating severe mitochondrial damage and loss of membrane potential. All changes described above took place in viable (propidium iodide-negative) cells. The experiments demonstrate that severe perturbations of intracellular Ca2+ distribution, particularly in the mitochondrial region, precede bleb formation and cell death in the course of development of toxicity by DCVC and DCVHC. PMID- 2233688 TI - Developmental expression and in situ localization of the phenobarbital-inducible rat hepatic mRNAs for cytochromes CYP2B1, CYP2B2, CYP2C6, and CYP3A1. AB - In this study we examined the differential hepatic expression of four phenobarbital (PB)-inducible rat cytochrome P450 genes, CYP2B1, CYP2B2, CYP2C6, and CYP3A1. The mRNAs encoding these cytochromes were analyzed in the liver with respect to PB responsiveness, developmental expression, and in situ localization. Utilization of the polymerase chain reaction enabled assessment of specific hepatic mRNA expression patterns during early development that were not detectable with standard Northern blot or slot-blot procedures. The polymerase chain reaction data demonstrated that fetal liver from day 15 of gestation was responsive to the inductive effects of transplacental PB administration. Both constitutive and PB-induced levels of each mRNA increased with increasing developmental age, reaching maximal levels approximately 3 weeks postpartum. An exception to this trend was observed for rats of gestational day 22, which exhibited transiently increased constitutive levels of CYP2B1, CYP2B2, and CYP3A1 mRNAs, such that PB-induced levels were not elevated over those observed in untreated animals. In situ hybridization data, obtained with livers form 6-week postpartum animals, revealed striking differences in regional distributions among the cytochrome P450 transcripts. Whereas patterns of PB-induced expression of CYP2C6 mRNAs were relatively homogeneous across the hepatic lobule, CYP3A1 mRNAs in PB-treated livers demonstrated marked centrilobular localization. These results were in contrast to data obtained previously for PB-inducible CYP2B1 and CYP2B2 mRNAs, which were distributed homogeneously across the hepatic lobule except for cells in the immediate vicinity of the periportal tract. PMID- 2233689 TI - Multiple forms of biliverdin reductase: age-related change in pattern of expression in rat liver and brain. AB - Biliverdin reductase is the dual nucleotide-dependent cytosolic enzyme that converts biliverdin to the bile pigment, bilirubin, and displays extensive microheterogeneity in rat organs. The enzyme is unique in having two pH optima. The present study reports on the tissue-dependent pattern of developmental expression of the reductase in rat liver and brain. When analyzed by Western immunoblotting, two closely migrating immunoreactive proteins were detected in the liver cytosol during the first 2-3 weeks after birth; the protein with greater mobility was not detected in the liver of adult aged animals (6 months old) and was present at low levels in rats during the first week of life. The faster migrating protein was not detected in the brain cytosol at any stage of development. Furthermore, in the brain the total amount of enzyme protein increased as the animal matured, whereas in the liver the enzyme protein level decreased with age. When the purified enzyme was analyzed, age-related changes in the variant composition of the enzyme in the liver were noted. Although in both adult and newborn animals (14 days old) the purified enzyme, when subjected to isoelectric focusing, separates into five net charge forms (pl 6.23, 5.91, 5.76, 5.61, and 5.48), the relative abundance of the variants notably differed in the two preparations. In addition, when the purified preparations were subjected to two-dimensional electrophoresis, although both purified preparations separate into three molecular weight forms (Mr 30,400, 30,700, and 31,400) one species (Mr 31,400, pl = 5.77), which was very prominently expressed in the newborn, was essentially absent in the adult. Biliverdin reductase activity of the liver cytosol with both NADPH (pH 8.7) and NADH (pH 6.7) exhibited developmental changes, with the activity increasing after birth, reaching a peak on day 14, and decreasing to low levels in the adult. The existence of a close correlation between development of biliverdin reductase activity in the brain and liver and that of heme oxygenase in these organs is noted. The suggestion is made that the reductase is not a passive component of the heme degradation pathway; rather, its activity could become limiting in the elimination of heme degradation products. PMID- 2233690 TI - Hemin administration to rats reduces levels of hepatic mRNAs for phenobarbitone inducible enzymes. AB - The levels of hepatic mRNAs for several enzymes involved in drug metabolism were measured following administration to rats of either phenobarbitone or 2-allyl-2 isopropylacetamide. There was a substantial elevation in the mRNA levels for cytochromes P450 IIB1, IIB2, and IIIA1, epoxide hydrolase, glutathione-S transferase Ya/Yc subunit, UDP-glucuronosyltransferase isoenzyme (UDPGTr-2), NADPH-cytochrome P450 oxidoreductase, and 5-aminolevulinate synthase. When rats were treated with hemin, together with inducing drug, there was a marked reduction in the induced levels of these mRNAs, with decreases in the range of 55 95%. Basal levels of these mRNAs in the noninduced rat liver were also lowered by hemin administration. Nuclear run-on transcriptional experiments showed that hemin administration substantially lowered both the basal and drug-induced transcriptional activities of the genes for cytochrome P450IIB1/IIB2 and 5 aminolevulinate synthase. In contrast, the mRNA for heme oxygenase was elevated by hemin treatment, whereas the mRNA levels of beta-actin, albumin, and ornithine transcarbamylase, used as controls, were not affected. Treatment of rats with clofibrate resulted in increased levels of mRNA for cytochrome IVA1 and, in addition, those for cytochromes P450IIB1 and P450IIB2. Hemin administration repressed the induction of mRNA levels for cytochromes P450IIB1 and IIB2 but not that for cytochrome P450 IVA1. Additionally, the induction of P450IAI by beta naphthoflavone was not affected by hemin. The results suggest that heme may negatively control the induction of cytochromes P450IIB1 and IIB2 and other hepatic enzymes by phenobarbitone and phenobarbitone-like drugs and perhaps play a role in regulating drug metabolism. There is, however, no evidence at present as to whether heme has a direct role in such a mechanism or whether injected hemin promotes a secondary response. PMID- 2233691 TI - Epidermal growth factor stimulates linoleic acid metabolism in BALB/c 3T3 fibroblasts. AB - One response of BALB/c 3T3 cells to epidermal growth factor (EGF) is the release and subsequent metabolism of arachidonic acid. Prostaglandins generated from EGF treatment appear to play a role in the mitogenic signal. Lipoxygenase inhibitors (nordihydroguaiaretic acid and 5,8,11,14-eicosatetraynoic acid) were previously shown to be very effective in blocking EGF-stimulated DNA synthesis; however, only low levels of lipoxygenase-derived arachidonate metabolites were detected. In an extension of these investigations, we have now found that EGF stimulates lipoxygenase metabolites of linoleic acid in BALB/c 3T3 fibroblasts. In the presence of EGF (10 ng/ml), the cells converted 10-15% of exogenous linoleic acid (10 microM) to hydroxy fatty acids that were isolated on reverse phase high performance liquid chromatography. No linoleate metabolites were detected in the absence of EGF. The isolated compounds were characterized further by straight phase high performance liquid chromatography, UV spectroscopy, and gas chromatography-mass spectrometry analyses, and they were identified as 13 hydroxyoctadecadienoic acid and 9-hydroxyoctadecadienoic acid. The hydroxy metabolites and their hydroperoxy precursors produced a 2- to 4-fold potentiation of EGF-stimulated [3H]thymidine incorporation in BALB/c 3T3 cells. These linoleate derivatives stimulated DNA synthesis at concentration ranges of 10(-8) to 10(-6) M. Thus, linoleic acid metabolism might be an important element in the EGF-regulated cascade of biochemical events leading to fibroblast mitogenesis. PMID- 2233692 TI - Quantitative molecular analysis predicts 5-hydroxytryptamine3 receptor binding affinity. AB - A quantitative molecular model was derived to predict drug affinities for 5 hydroxytryptamine3 (5-HT3) receptors. The model was based on the molecular characteristics of a "learning set" of 40 pharmacological agents that had been analyzed previously in radioligand binding studies. Molecules were analyzed for various structural features, i.e., the presence of a benzenoid ring and nitrogen atom, substitutions on the benzenoid ring, the location of the substitutions on the nitrogen, and the molecular characteristics of the most direct pathway from the benzenoid ring to the nitrogen. Weighting factors, based on published 5-HT3 receptor affinity data, were then assigned to each of 10 molecular characteristics. The derived computational model predicts accurately the affinities of the learning set for the 5-HT3 receptor (r = 0.98; p less than 0.001). The computational model was then used to predict the receptor affinities of a "test set" of 40 pharmacological agents. The predicted values for these agents also correlate significantly (r = 0.83; p less than 0.001) with drug affinities for the 5-HT3 receptor, as determined by radioligand binding assays. This first line screening approach allows for the accurate prediction of drug affinities based on molecular characteristics with minimal dependence upon animal tissues or radioactivity. PMID- 2233693 TI - Inhibition of ribonucleotide reduction in CCRF-CEM cells by 2',2' difluorodeoxycytidine. AB - The new deoxycytidine analogue 2',2'-difluorodeoxycytidine (dFdC) is a specific inhibitor of DNA synthesis that has marked cytotoxicity and therapeutic activity. A 2-hr incubation with 0.1-10 microM dFdC decreased cellular viability 78-97%. This treatment reduced deoxynucleoside triphosphate pools, similar to the action of the ribonucleotide reductase inhibitor hydroxyurea. The most pronounced decrease occurred in the dCTP pool, quantitatively followed by the decrease of dATP, dGTP, and dTTP. In contrast, inhibition of DNA synthesis by arabinosylcytosine did not affect the dCTP level, whereas dATP, dGTP, and dTTP pools increased, but less than 2-fold. The incorporation of [5-3H]cytidine into the dCTP pool, a measure of ribonucleotide reductase activity in whole cells, was reduced to 3% of controls by 0.1 microM dFdC, but to only 40% by 0.1 microM ara C. Each drug decreased incorporation of [5-3H]cytidine into DNA to a similar extent (greater than 94%), suggesting limitation by a reaction proximal to this step. The cellular concentration of dFdC 5'-diphosphate was 0.3 microM at 50% inhibition of the in situ activity of ribonucleotide reductase. Direct assays of partially purified ribonucleoside diphosphate reductase (EC 1.17.4.1) demonstrated 50% inhibition by 4 microM dFdC 5'-diphosphate; dFdC 5'-triphosphate was much less inhibitory. We conclude that dFdC 5'-diphosphate acts as an inhibitor of ribonucleoside diphosphate reductase. PMID- 2233694 TI - Stereoselective S-oxygenation of 2-aryl-1,3-dithiolanes by the flavin-containing and cytochrome P-450 monooxygenases. AB - The reaction of NalO4, highly purified flavin-containing monooxygenase (EC 1.14.13.8), and microsomes from hog liver with 2-aryl-1,3-dithiolanes and 2-aryl 1,3-dithiolane S-oxides was investigated. The initial rates determined for the microsome- and purified flavin-containing monooxygenase-catalyzed rate of S oxidation of para-substituted 2-aryl-1,3-dithiolanes were similar, demonstrating that S-oxidation of these substrates occurred with similar velocities at saturating concentrations of substrate and, at least for the first S-oxidation, the reaction was insensitive to the nature of the para-substituent. The diastereoselectivity of S-oxygenation of 2-aryl-1,3-dithiolanes was determined and, in general, a marked preference for addition of oxygen to the sulfide sulfur atom was observed to occur trans to the aryl groups. In all cases examined, enantioselective enzymatic S-oxidation was observed. For S-oxide formation in microsomes, the data provided evidence for a minor role of cytochrome P-450 in S oxide formation, but the flavin-containing monooxygenase was mainly responsible for production of S-oxide. In contrast to previous reports, the enantioselectivity of S-oxidation catalyzed by highly purified cytochrome P 450IIB-1 and cytochrome P-450IIB-10 was not always opposite to that catalyzed by hog liver flavin-containing monooxygenase activity. 2-Aryl-1,3-dithiolane S oxides were also oxidized a second time by NalO4, microsomes, or highly purified flavin-containing monooxygenase from hog liver but not cytochrome P-450IIB-1 or P 450IIB-10. The rate of the second oxidation was 10-15-fold slower than the corresponding first S-oxidation and S,S'-dioxide formation was markedly dependent on the electronic nature of the para-substituent (Hammett correlation rho value of -1.3 and -1.1 for microsomes and highly purified flavin-containing monooxygenase from hog liver, respectively). The large dependence of the rate of S,S'-dioxide formation on the nature of the para-substituent demonstrates that velocity values at saturating concentrations of S-oxide were not the same for all 2-aryl-1,3-dithiolane S-oxides and suggests that the chemical nature of the 2 aryl-1,3-dithiolane S-oxide contributes to the rate-determining step of this enzymatic reaction. PMID- 2233695 TI - Cross-reactivity of antibodies raised against acetaldehyde adducts of protein with acetaldehyde adducts of phosphatidyl-ethanolamine: possible role in alcoholic cirrhosis. AB - This study measured the possible cross-reactivity of hapten-specific IgG antibodies purified from the sera of rabbits sensitized to an albumin acetaldehyde conjugate [N-ethyl-rabbit serum albumin (N-ethyl-RSA)] with acetaldehyde-phosphatidylethanolamine adducts. The N-ethyl-RSA was coupled to an Affigel-10 column to affinity purify the IgG (anti-N-ethyl-RSA IgG). Dioleoyl phosphatidylethanolamine (DOPE) was reacted with acetaldehyde to form a Schiff base, which was reduced to N-ethyl-DOPE, purified by high pressure liquid chromatography, and analyzed with direct chemical ionization mass spectrometry. Lamellar liposomes containing either 5% by weight N-ethyl-DOPE and 95% egg phosphatidylcholine or a mixture of 5% N-ethyl-DOPE, 71% DOPE, and 24% dioleoylphosphatidylcholine, as well as hexagonal phase micelles containing 5% N ethyl-DOPE and 95% DOPE, were prepared by sonication. Anti-N-ethyl-RSA IgG was then incubated with each of these lipid mixtures for 30 min, a fluorescein conjugated goat anti-rabbit IgG was added for an additional 30 min, and then binding of anti-N-ethyl-RSA IgG to N-ethyl-DOPE in the liposomes or micelles was measured by flow cytometry. Anti-N-ethyl-RSA IgG bound to N-ethyl-DOPE in both vesicles and hexagonal phase micelles, but the affinity was 16 times greater for the hapten in the hexagonal phase. This result demonstrates that physical presentation of the hapten can affect antibody recognition and that antibodies raised against N-ethyl-RSA can cross-react with acetaldehyde-phospholipid adducts. PMID- 2233697 TI - [3H]-DOB(4-bromo-2,5-dimethoxyphenylisopropylamine) and [3H] ketanserin label two affinity states of the cloned human 5-hydroxytryptamine2 receptor. AB - The binding properties of the 5-hydroxytryptamine2 (5-HT2) receptor have been the subject of much interest and debate in recent years. The hallucinogenic amphetamine derivative 4-bromo-2,5-dimethoxyphenylisopropylamine (DOB) has been shown to bind to a small number of binding sites with properties very similar to [3H]ketanserin-labeled 5-HT2 receptors, but with much higher agonist affinities. Some researchers have interpreted this as evidence for the existence of a new subtype of 5-HT2 receptor (termed 5-HT2A), whereas others have interpreted these data as indicative of agonist high affinity and agonist low affinity states for the 5-HT2 receptor. In this investigation, a cDNA clone encoding the serotonin 5 HT2 receptor was transiently transfected into monkey kidney Cos-7 cells and stably transfected into mouse fibroblast L-M(TK-) cells. In both systems, expression of this single serotonin receptor cDNA led to the appearance of both [3H]DOB and [3H]ketanserin binding sites with properties that matched their binding characteristics in mammalian brain homogenates. Addition of guanosine 5' (beta, gamma-imido) triphosphate [Gpp(NH)p] to this system caused a rightward shift and steepening of agonist competition curves for [3H] ketanserin binding, converting a two-site binding curve to a single low affinity binding state. Gpp(NH)p addition also caused a 50% decrease in the number of high affinity [3H]DOB binding sites, with no change in the dissociation constant of the remaining high affinity states. These data on a single human 5-HT2 receptor cDNA expressed in two different transfection host cells indicate that [3H]DOB and [3H]ketanserin binding reside on the same gene product, apparently interacting with agonist and antagonist conformations of a single human 5-HT2 receptor protein. These observations are consistent with the classical view of interconvertible agonist affinity states of GTP-binding protein-coupled receptors and strongly support the "two state" over the "two receptor" model for DOB binding to the 5-HT2 receptor. PMID- 2233696 TI - 4-[125I]iodo-(2,5-dimethoxy)phenylisopropylamine and [3H]ketanserin labeling of 5 hydroxytryptamine2 (5HT2) receptors in mammalian cells transfected with a rat 5HT2 cDNA: evidence for multiple states and not multiple 5HT2 receptor subtypes. AB - Evidence has accumulated indicating that the radioactive hallucinogens 4-bromo [3H](2,5-dimethoxy)phenylisopropylamine ([3H]DOB) and 4-[125I]iodo-(2,5 dimethoxy)phenylisopropylamine ([125I]DOI) label an agonist high affinity state of the 5-hydroxytryptamine2 (5HT2) receptor and [3H]ketanserin labels both agonist high and low affinity states. Recently, an alternative hypothesis has been put forward proposing that the radioactive hallucinogens are labeling a 5HT2 receptor subtype distinct from the receptor labeled by [3H]ketanserin. In order to provide definitive evidence as to which of these hypotheses is correct, the rat 5HT2 receptor gene was transfected into NIH-3T3 (mammalian fibroblast) cells and COS (green monkey kidney) cells. Neither nontransfected cell type expresses 5HT2 receptors; the transfected cells expressed high affinity binding sites for both [125I] DOI (KD = 0.8 nM and Bmax = 363 fmol/mg in NIH-3T3 cells; KD = 0.2 nM and Bmax = 26 fmol/mg in COS cells) and [3H]ketanserin (KD = 0.4 nM and Bmax = 5034 fmol/mg in NIH-3T3 cells; KD = 1.0 nM and Bmax = 432 fmol/mg in COS cells). The affinities of agonists and antagonists for the [125I]DOI-labeled receptor were significantly higher than for the [3H]ketanserin-labeled receptor. The affinities of agonists and antagonists for these binding sites were essentially identical to their affinities for the sites radiolabeled by these radioligands in mammalian brain homogenates. The [125I]DOI binding was guanyl nucleotide sensitive, indicating a coupling to a GTP-binding protein. These data indicate that the 5HT2 receptor gene product contains both the guanyl nucleotide-sensitive [125I]DOI binding site and the [3H]ketanserin binding site. Therefore, these data indicate that the 5HT2 receptor gene product can produce a high affinity binding site for the phenylisopropylamine hallucinogen agonists as well as for the 5HT2 receptor antagonists. These results strongly support the two-state hypothesis for the 5HT2 receptor and do not support the multiple 5HT2 receptor subtype hypothesis. PMID- 2233698 TI - Long lasting increase in neuropeptide Y gene expression in rat adrenal gland with reserpine treatment: positive regulation of transsynaptic activation and membrane depolarization. AB - To elucidate how the neuropeptide Y (NPY) gene is regulated by physiological/pharmacological changes in neural functions, the expression and regulation of the NPY gene were studied by measuring changes in the abundances of NPY and NPY mRNA in the adrenal gland and brain regions of rats in vivo and in PC12 rat pheochromocytoma cells after reserpine treatment. Long term treatment with reserpine in vivo, which causes hypotension and increased splanchnic nerve activity, induced prolonged increases in the abundance of NPY mRNA and putative NPY pre-mRNA, with concomitant increases in NPY, in the adrenal gland in a tissue dependent manner but caused no changes in the abundance of beta-actin mRNA. Transection of the splanchnic nerves almost completely (76%) prevented the reserpine-induced increases in the abundance of NPY mRNA and NPY pre-mRNA, but denervation alone did not affect their steady state levels. These results suggested that increased activity of the splanchnic nerves regulates NPY gene expression positively in the adrenal gland, probably at the level of transcription. In PC12 cells, reserpine decreased the abundance of NPY mRNA directly, but nicotinic receptor activation increased its abundance transiently and the persistent membrane depolarization increased its abundance markedly. Thus, NPY gene expression is positively regulated by membrane depolarization via increased transsynaptic activation with reserpine. PMID- 2233699 TI - Immunochemical analysis of a cytochrome P-450IA1 homologue in human lung microsomes. AB - The monoclonal antibody MAb 1-7-1, which specifically binds to cytochromes P 450IA1 and P-450IA2 in 3-methylcholanthrene-induced rat liver microsomes, was used to identify a cytochrome P-450IA1 homologue in human lung microsomes. Although MAb 1-7-1 had similar affinity constants for human and rat microsomes, the amount bound to human lung microsomes was severalfold lower than that bound to microsomes from untreated rat or rabbit lung and much lower than the amount bound to 3-methylcholanthrene-induced rat lung or liver microsomes. The amount bound to untreated baboon lung microsomes was similar to that bound to human lung microsomes. Three cytochrome P-450IA1-catalyzed activities, 7-ethoxyresorufin O deethylase, 7-ethoxycoumarin, O-deethylase, and aryl hydrocarbon hydroxylase, were measurable in human lung microsomes, but the cytochrome P-450IA2-dependent activity acetanilide 4-hydroxylase was not. MAb 1-7-1 inhibited, and its binding correlated strongly with, 7-ethoxyresorufin O-deethylase activity (r = 0.92, p less than 0.01) in human lung microsomes. 7-Ethoxyresorufin O-deethylase activities in human lung were similar to those measured in untreated baboon lung but considerably lower than those present in untreated rabbit lung, untreated or 3-methylcholanthrene-induced rat lung and liver, or human liver. We conclude that MAb 1-7-1 recognizes a cytochrome P-450IA1 homologue in human lung and that no cytochrome P-450IA2 homologue is detected. Cytochrome P-450IA1 is expressed in human lung at relatively low levels, similar to those observed in untreated primate (baboon) lung. The majority of the 19 human lung samples examined do not exhibit a permanent polycyclic aromatic hydrocarbon-induced state with respect to this isozyme. PMID- 2233700 TI - Positive cooperativity in the binding of alcuronium and N-methylscopolamine to muscarinic acetylcholine receptors. AB - The effect of the neuromuscular blocker alcuronium on the binding of N-[3H] methylscopolamine [( 3H]NMS) and l-[3H]quinuclidinylbenzilate ([3H]QNB) to muscarinic binding sites in rat heart atria, longitudinal smooth muscle of the ileum, cerebral cortex, cerebellum, and submaxillary glands was measured using filtration techniques. In the presence of 10(-5) M alcuronium, the binding of [3H]NMS (which was present at a subsaturating concentration of 2 x 10(-10) M) was increased 5.3-fold in the atria and smooth muscle and 3-fold in the cerebellum; no increase was observed in the brain cortex and salivary glands. The binding of [3H]NMS was inhibited at 10(-3) M and higher concentrations of alcuronium. The rates of [3H]NMS association to and dissociation from muscarinic binding sites in the atria were diminished by 10(-5) M alcuronium. Scatchard plots of [3H]NMS binding data obtained with and without 10(-5) M alcuronium indicated that the maximum number of binding sites was not altered by the drug, whereas the apparent Kd for [3H]NMS was diminished. In contrast to [3H] NMS, the effects of alcuronium on the binding of [3H]QNB were only inhibitory. The concentration of alcuronium required to diminish the binding of [3H]QNB by 50% (IC50) was 4-7 microM in the atria, ileal smooth muscle, and the cerebellum, 140 microM in the brain cortex, and 1200 microM in the parotid gland. The results suggest that the binding of low concentrations of alcuronium to muscarinic receptors in the heart, ileal smooth muscle, and cerebellum allosterically increases the affinity of muscarinic receptors towards [3H]NMS, although not [3H]QNB. At high concentrations, alcuronium inhibits the binding of muscarinic ligands, presumably by competition for the classical muscarinic binding site. Positive cooperativity induced by alcuronium appears to be specific for the m2 (cardiac) subtype of muscarinic receptors. PMID- 2233701 TI - Structure-function relationships of hydroxylated metabolites of tamoxifen that control the proliferation of estrogen-responsive T47D breast cancer cells in vitro. AB - Several hydroxylated derivatives of tamoxifen were tested for their effects on the growth of T47D human breast cancer cells in vitro. Compounds containing a fused seven-membered ring were used to prevent isomerization of the triphenyl ethylenes at the double bond. This stable structure permitted the determination of the activity of the cis and trans forms of tamoxifen and the true activity of two of its metabolites, 4-hydroxytamoxifen and metabolite E. Estradiol stimulates the growth of T47D cells 3-4-fold over control after 6 days of treatment (EC50 = congruent to 3 x 10(-12) to 3 x 10(-11) M, depending upon the particular experiment). The fixed ring form of the trans isomer of tamoxifen is an antiestrogen, whereas the cis isomer is estrogenic. Fixed ring-trans-4 hydroxytamoxifen is a potent antiestrogen, and its cis isomer is a weak antiestrogen (IC50 congruent to 4 x 10(-8) to 2 x 10(-7) M). The fixed ring form of trans-metabolite E (tamoxifen without the dimethylaminoethane side chain) is only a weak partial estrogen agonist, whereas the fixed ring derivative of its cis isomer is a potent estrogen agonist (EC50 congruent to 4 x 10(-12) to 1 x 10( 11) M). These studies have determined the true biological activities of the hydroxylated derivatives of tamoxifen. This information will be valuable for the development of drug receptor models and will be particularly useful when the three-dimensional structure of the receptor complex is determined. PMID- 2233703 TI - Regulatory volume decrease of pancreatic beta-cells involving activation of tetraethylammonium-sensitive K+ conductance. AB - Beta-cell-rich pancreatic islets from ob/ob-mice were used for evaluating the early effects of hypotonic stress. The beta-cells responded to an abrupt lowering of the osmotic pressure by 102 mOsm with both a transient stimulation of insulin release (peak value 25 times above basal) and a loss of potassium without major effects on sodium. The secretory response was obtained also in the presence of 100 microM quinine or 20 mM tetraethylammonium+. The loss of potassium was not affected by 20 mM glucose or 10 microM bumetanide, but became less apparent in the presence of 100 microM quinine and disappeared when the islets were exposed to 20 mM tetraethylammonium+. Amiloride and high concentrations of the hypoglycemic sulfonylureas tolbutamide and glibenclamide had only a slight suppressive action on potassium mobilization. Patch clamp analyses revealed an increased frequency of small channel openings after exposure to the hypotonic medium. It is concluded that the pancreatic beta-cells have the ability for a regulatory volume decrease involving activation of tetraethylammonium-sensitive K+ conductance. The stimulation of insulin release obtained by lowering the osmotic pressure seems to be related to the entry of water rather than to the ion movements responsible for the readjustment of the beta-cell volume. PMID- 2233702 TI - Molecular events regulating messenger RNA stability in eukaryotes. AB - The regulation of mRNA turnover plays a major role in the overall control of gene expression. Transcriptional control of eukaryotic gene regulation by external and/or internal stimuli has received considerable attention and the purpose of this review is to highlight recent work elucidating the mechanisms underlying the steady-state levels of mRNAs in the cytoplasm. Protection of mRNA from the action of nucleases as it passes from the nucleus to the ribosomes for translation is achieved, at least in part, by its union with mRNA binding proteins and the presence of poly(A) tail. The half-life of a message represents a balance between the transcriptional activity and intracellular degradative processes. These properties can be modulated by the presence of specific nucleotide sequences in a mRNA along with cis- and trans-acting elements and accompanied by post translational feed back mechanisms. Presently, various regulatory mechanisms involved in the mRNA decay process are ill-defined. The work described here illustrates the complexity of this emerging field of study and outlines its contribution to our understanding of gene regulation in eukaryotes. PMID- 2233704 TI - Characterization and analysis of the subclasses and molecular species of choline phosphoglycerides from porcine heart by successive chemical hydrolyses and reverse phase high-performance liquid chromatography. AB - Choline phosphoglycerides (CPG) represent the major fraction of heart phospholipids. Since depletion of membrane phospholipids and accumulation of lyso compounds, particularly lysophosphatidylcholines, have been implicated in arrhythmogenesis, it was of great interest to study the composition of this major phospholipid fraction of the heart at a molecular level in an established animal model. The data presented here describe the first report on the detailed chemical examination of CPG and resolution, characterization and quantitative analysis of the molecular species of this phospholipid fraction from porcine heart by high performance liquid chromatography (HPLC). This fraction constitutes 37.5 +/- 0.7% (n = 21) of the total phospholipids and upon successive mild acid and alkaline hydrolyses revealed the presence of essentially three subclasses: diacyl-, alkenylacyl-, and alkylacyl glycerophosphorylcholines, in a relative abundance of 57.7 +/- 2.2% (n = 8), 37.3 +/- 1.3% (n = 8) and 4.6 +/- 0.2% (n = 8), respectively. The fourth subclass, dialkyl CPG was found only in minute amounts (0.43 +/- 0.05%, n = 8) and the presence of dialkenyl and alkenylalkyl analogues could not be detected. Alternatively, by converting the CPG fraction to benzoate derivatives after phospholipase C digestion, it was possible to isolate and quantitate subclass composition by TLC/spectroscopy or both subclass compositions and molecular species analysis by HPLC directly by a UV detector online with the column. By these techniques, subclass composition was found to be very similar to that obtained by the chemical hydrolysis technique. By HPLC, up to 25 species can be identified and quantitated in each subclass, their identity being confirmed by gas-liquid chromatography, after their isolation from the column. The analyses showed that up to 74% of the diacyl moiety consisted of 16:0-18:2 (34%), 16:0 18:1 (27%), and 18:0-18:2 (13%) species, while the major species of the alkenylacyl moiety were 16:0-18:2 (44%) 16:0-18:1 (13%), 16:0-20:4 (12%) and 18:1 18:2 (9%) making up more than 75% of the total mass of this subclass. The major molecular species of the alkylacyl moiety was 16:0-18:2, constituting up to 47% of this fraction, while others constituted about 10% (16:0-18:1), 9% (18:1-18:2), 8% (16:0-20:4) and 6% (18:0-18:2), making up 80% of the total mass. The ether chain composition of akylacyl CPG whether determined after isolation of this fraction by the chemical hydrolysis technique or by HPLC was indistinguishable.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2233705 TI - The kinetics of fibronectin synthesis and release in normal and tumor promoter treated human lung fibroblasts. AB - The present study is a detailed kinetic analysis of the synthesis, release and multimerization of fibronectin (FN) in normal and tumor promoter-treated human lung fibroblasts. Pulse/chase and surface labeling experiments were performed to follow the fate of both newly synthesized and preexisting cell-surface FN over time. The majority of FN (80%) left the intracellular compartment within one hour of synthesis. However, the rate of direct secretion was very low and after one hour, 70% of newly synthesized FN was still at the cell surface. This material was primarily dimeric. Dimeric and multimeric (very high molecular weight) FN was detectable at the cell surface and in the medium 4 hours after synthesis. Pulse labeled FN multimer levels peaked at 12 hours and declined thereafter. After 24 hours, 85% of pulse-labeled FN had been shed into the medium and the labeled FN remaining at the cell surface was primarily multimeric. Surface labeling experiments confirmed that the majority of FN resides at the cell surface prior to release into the medium. One hour treatment with the phorbol ester tumor promoter, 12-0-tetradecanoyl phorbol-13-acetate (TPA), stimulated a nine-fold increase in release of preexisting, dimeric cell-surface FN (125I-labeled). The major effect of longer term TPA treatment up to nine hours was continued depletion of dimeric cell-surface FN. Increased release of cell-surface multimeric FN was also stimulated by TPA, but to a much lesser extent. Release of newly synthesized (pulse-labeled) dimeric FN was also stimulated by TPA though much less than pre-existing FN, and TPA treatment produced a small decrease in the steady-state level of multimeric FN. Thus, preexisting cell-surface FN and newly synthesized FN differ dramatically in their susceptibility to TPA treatment. PMID- 2233706 TI - Protein kinase C does not regulate diacylglycerol metabolism in aortic smooth muscle cells. AB - The effect of a reduction in protein kinase C activity on the metabolism of exogenous [3H]diC8 by freshly isolated smooth muscle cells from rabbit aorta and cultured A10 smooth muscle cells was determined. The metabolism of [3H]diC8 by both smooth muscle cell preparations was predominantly by hydrolysis to yield monoC8 and glycerol (lipase pathway); very little radioactivity was incorporated into phospholipids. Diacylglycerol lipase activity measured in vitro with A10 cell homogenates was much greater than diacylglycerol kinase activity. The addition of the protein kinase C inhibitor H-7 to incubations of isolated aortic smooth muscle cells and cultured A10 cells had no significant effect on the metabolism of [3H]diC8. Protein kinase C activity in cultured A10 cells preincubated for 20 h with a phorbol ester was reduced to 14% of control as a consequence of down-regulation, but diC8 metabolism was not changed. Therefore, protein kinase C does not regulate the metabolism of diacylglycerols in aortic smooth muscle cells. PMID- 2233707 TI - Lymphocyte calcium extrusion: kinetic and thermodynamic measurements using ratiometric dual-emission spectrofluorometry. AB - A method is described for monitoring intracellular ionized calcium (Ca2+) and determining kinetic and thermodynamic parameters of Ca2(+)-extrusion from intact lymphocytes. The method uses ratiometric spectrofluorometry and the fluorescent Ca2+ dye indo-1. Lymphocytes were loaded with calcium and placed in a low calcium medium. A novel formula for calculation of intracellular Ca2+ that corrects for background fluorescence and fluorescence quenching was used. Calcium extrusion resulted in exponential decrease in cytoplasmic Ca2+ with a rate constant of 0.031 +/- 0.003 sec-1, maximal rate of 23 +/- 7 nM/sec, dissociation constant of 366 +/- 63 nM, Hill coefficient of 2.3 +/- 0.4, Q10 of 2.58 +/- 0.28, and activation energy of 18.3 Kcal/mol. This method should allow for characterization of the Ca2(+)-extrusion system of lymphocytes and may be applicable to other blood cell types. PMID- 2233709 TI - Tissue-specific expression from a compound TATA-dependent and TATA-independent promoter. AB - We have found that the mouse metallothionein-I (MT-I) gene promoter functions in an unusual, compound manner. It directs both TATA-dependent and TATA-independent modes of transcription in vivo. The TATA-dependent message is initiated at the previously characterized +1 transcription start site and is the predominant species in most tissues. In many cell types it is metal inducible. The TATA independent initiation sites are distributed over the 160 bp upstream of the previously characterized +1 start site, and the RNA products are present in all tissues examined. Only in testis, however, do the TATA-independent transcripts predominate, accumulating to highest levels in pachytene-stage meiotic cells and early spermatids. Unlike the TATA-dependent +1 transcript, these RNAs are not induced by metal, even in cultured cells in which the +1 species is induced. Transfection studies of site-directed mutants show that destruction of the TATA element drastically alters the ratio of the two RNA classes in cells in which the +1 transcripts normally dominates. In TATA-minus mutants, the TATA-independent RNAs become the most prevalent, although they remain refractory to metal induction. Thus, the MT-I promoter utilizes two different types of core promoter function within a single cell population. The two different types of core promoter respond very differently to environmental stimuli, and the choice between them appears to be regulated in a tissue-specific fashion. PMID- 2233708 TI - The SNF5 protein of Saccharomyces cerevisiae is a glutamine- and proline-rich transcriptional activator that affects expression of a broad spectrum of genes. AB - The Saccharomyces cerevisiae SNF5 gene affects expression of both glucose- and phosphate-regulated genes and appears to function in transcription. We report the nucleotide sequence, which predicts that SNF5 encodes a 102,536-dalton protein. The N-terminal third of the protein is extremely rich in glutamine and proline. Mutants carrying a deletion of the coding sequence were viable but grew slowly, indicating that the SNF5 gene is important but not essential. Evidence that SNF5 affects expression of the cell type-specific genes MF alpha 1 and BAR1 at the RNA level extends the known range of SNF5 function. SNF5 is apparently required for expression of a wide variety of differently regulated genes. A bifunctional SNF5 beta-galactosidase fusion protein was localized in the nucleus by immunofluorescence. No DNA-binding activity was detected for SNF5. A LexA-SNF5 fusion protein, when bound to a lexA operator, functioned as a transcriptional activator. PMID- 2233710 TI - Transcriptional activation of the human cytotoxic serine protease gene CSP-B in T lymphocytes. AB - The cytotoxic serine protease B (CSP-B) gene is activated during cytotoxic T lymphocyte maturation. In this report, we demonstrate that the PEER T-cell line (bearing gamma/delta T-cell receptors) accumulates CSP-B mRNA following exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA) and N6-2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (bt2cAMP) because of transcriptional activation of the CSP-B gene. TPA and bt2cAMP act synergistically to induce CSP-B expression, since neither agent alone causes activation of CSP-B transcription or mRNA accumulation. Chromatin upstream from the CSP-B gene is resistant to DNase I digestion in untreated PEER cells, but becomes sensitive following TPA-bt2cAMP treatment. Upon activation of PEER cells, a DNase I-hypersensitive site forms upstream from the CSP-B gene within a region that is highly conserved in the mouse. Transient transfection of CSP-B promoter constructs identified two regulatory regions in the CSP-B 5'-flanking sequence, located at positions -609 to -202 and positions -202 to -80. The region from -615 to -63 is sufficient to activate a heterologous promoter in activated PEER cells, but activation is orientation specific, suggesting that this region behaves as an upstream promoter element rather than a classical enhancer. Consensus AP-1, AP-2, and cAMP response elements are found upstream from the CSP-B gene (as are several T-cell-specific consensus elements), but the roles of these elements in CSP-B gene activation have yet to be determined. PMID- 2233711 TI - Molecular genetic analysis of Saccharomyces cerevisiae C1-tetrahydrofolate synthase mutants reveals a noncatalytic function of the ADE3 gene product and an additional folate-dependent enzyme. AB - In eucaryotes, 10-formyltetrahydrofolate (formyl-THF) synthetase, 5,10-methenyl THF cyclohydrolase, and NADP(+)-dependent 5,10-methylene-THF dehydrogenase activities are present on a single polypeptide termed C1-THF synthase. This trifunctional enzyme, encoded by the ADE3 gene in the yeast Saccharomyces cerevisiae, is thought to be responsible for the synthesis of the one-carbon donor 10-formyl-THF for de novo purine synthesis. Deletion of the ADE3 gene causes adenine auxotrophy, presumably as a result of the lack of cytoplasmic 10 formyl-THF. In this report, defined point mutations that affected one or more of the catalytic activities of yeast C1-THF synthase were generated in vitro and transferred to the chromosomal ADE3 locus by gene replacement. In contrast to ADE3 deletions, point mutations that inactivated all three activities of C1-THF synthase did not result in an adenine requirement. Heterologous expression of the Clostridium acidiurici gene encoding a monofunctional 10-formyl-THF synthetase in an ade3 deletion strain did not restore growth in the absence of adenine, even though the monofunctional synthetase was catalytically competent in vivo. These results indicate that adequate cytoplasmic 10-formyl-THF can be produced by an enzyme(s) other than C1-THF synthase, but efficient utilization of that 10-formyl THF for purine synthesis requires a nonenzymatic function of C1-THF synthase. A monofunctional 5,10-methylene-THF dehydrogenase, dependent on NAD+ for catalysis, has been identified and purified from yeast cells (C. K. Barlowe and D. R. Appling, Biochemistry 29:7089-7094, 1990). We propose that the characteristics of strains expressing full-length but catalytically inactive C1-THF synthase could result from the formation of a purine-synthesizing multienzyme complex involving the structurally unchanged C1-THF synthase and that production of the necessary one-carbon units in these strains is accomplished by an NAD+ -dependent 5,10 methylene-THF dehydrogenase. PMID- 2233712 TI - Temperature-sensitive DNA mutant of Chinese hamster ovary cells with a thermolabile ribonucleotide reductase activity. AB - JB3-B is a Chinese hamster ovary cell mutant previously shown to be temperature sensitive for DNA replication (J. J. Dermody, B. E. Wojcik, H. Du, and H. L. Ozer, Mol. Cell. Biol. 6:4594-4601, 1986). It was chosen for detailed study because of its novel property of inhibiting both polyomavirus and adenovirus DNA synthesis in a temperature-dependent manner. Pulse-labeling studies demonstrated a defect in the rate of adenovirus DNA synthesis. Measurement of deoxyribonucleoside triphosphate (dNTP) pools as a function of time after shift of uninfected cultures from 33 to 39 degrees C revealed that all four dNTP pools declined at similar rates in extracts prepared either from whole cells or from rapidly isolated nuclei. Ribonucleoside triphosphate pools were unaffected by a temperature shift, ruling out the possibility that the mutation affects nucleoside diphosphokinase. However, ribonucleotide reductase activity, as measured in extracts, declined after cell cultures underwent a temperature shift, in parallel with the decline in dNTP pool sizes. Moreover, the activity of cell extracts was thermolabile in vitro, consistent with the model that the JB3-B mutation affects the structural gene for one of the ribonucleotide reductase subunits. The kinetics of dNTP pool size changes after temperature shift are quite distinct from those reported after inhibition of ribonucleotide reductase with hydroxyurea. An indirect effect on ribonucleotide reductase activity in JB3 B has not been excluded since human sequences other than those encoding the enzyme subunits can correct the temperature-sensitive growth defect in the mutant. PMID- 2233713 TI - The phenotype of the minichromosome maintenance mutant mcm3 is characteristic of mutants defective in DNA replication. AB - MCM3 is an essential gene involved in the maintenance of minichromosomes in yeast cells. It encodes a protein of 971 amino acids that shows striking homology to the Mcm2 protein. We have mapped the mcm3-1 mutation of the left arm of chromosome V approximately 3 kb centromere proximal of anp1. The mcm3-1 mutant was found to be thermosensitive for growth. Under permissive growth conditions, it was defective in minichromosome maintenance in an autonomously replicating sequence-specific manner and showed an increase in chromosome loss and recombination. Under nonpermissive conditions, mcm3-1 exhibited a cell cycle arrest phenotype, arresting at the large-bud stage with an undivided nucleus that had a DNA content of nearly 2n. These phenotypes are consistent with incomplete replication of the genome of the mcm3-1 mutant, possibly as a result of limited replication initiation at selective autonomously replicating sequences leading to cell cycle arrest before mitosis. The phenotype exhibited by the mcm3 mutant is very similar to that of mcm2, suggesting that the Mcm2 and Mcm3 protein may play interacting roles in DNA replication. PMID- 2233714 TI - Nucleosome depletion alters the chromatin structure of Saccharomyces cerevisiae centromeres. AB - Saccharomyces cerevisiae centromeric DNA is packaged into a highly nuclease resistant chromatin core of approximately 200 base pairs of DNA. The structure of the centromere in chromosome III is somewhat larger than a 160-base-pair nucleosomal core and encompasses the conserved centromere DNA elements (CDE I, II, and III). Extensive mutational analysis has revealed the sequence requirements for centromere function. Mutations affecting the segregation properties of centromeres also exhibit altered chromatin structures in vivo. Thus the structure, as delineated by nuclease digestion, correlated with functional centromeres. We have determined the contribution of histone proteins to this unique structural organization. Nucleosome depletion by repression of either histone H2B or H4 rendered the cell incapable of chromosome segregation. Histone repression resulted in increased nuclease sensitivity of centromere DNA, with up to 40% of CEN3 DNA molecules becoming accessible to nucleolytic attack. Nucleosome depletion also resulted in an alteration in the distribution of nuclease cutting sites in the DNA surrounding CEN3. These data provide the first indication that authentic nucleosomal subunits flank the centromere and suggest that nucleosomes may be the central core of the centromere itself. PMID- 2233715 TI - On the mechanism for efficient repression of the interleukin-6 promoter by glucocorticoids: enhancer, TATA box, and RNA start site (Inr motif) occlusion. AB - The feedback inhibition of interleukin-6 (IL-6) gene expression by glucocorticoids represents a regulatory link between the endocrine and immune systems. The mechanism of the efficient repression of the IL-6 promoter by dexamethasone (Dex) was investigated in HeLa cells transiently transfected with plasmid constructs containing different IL-6 promoter elements linked to the herpesvirus thymidine kinase gene (tk) promoter and the bacterial chloramphenicol acetyltransferase gene (cat) and cotransfected with cDNA vectors constitutively expressing either the active wild-type or inactive mutant human glucocorticoid receptor (GR). The induction by interleukin-1, tumor necrosis factor, phorbol ester, or forskolin of IL-6-tk-cat chimeric constructs containing a single copy of the IL-6 DNA segment from -173 to -151 (MRE I) or from -158 to -145 (MRE II), which derive from within the multiple cytokine- and second-messenger-responsive enhancer (MRE) region, was strongly repressed by Dex in a wild-type GR-dependent fashion irrespective of the inducer used. The induction by pseudorabies virus of an IL-6 construct containing the IL-6 TATA box and the RNA start site ("initiator" or Inr element) but not the MRE region was also repressed by Dex in the presence of wild-type GR. DNase I footprinting showed that the purified DNA binding fragment of GR bound across the MRE, the TATA box, and the Inr site in the IL-6 promoter; this footprint overlapped that produced by proteins present in nuclear extracts from uninduced or induced HeLa cells. Imperfect palindromic nucleotide sequence motifs moderately related to the consensus GR-responsive element (GRE) motif were present at the Inr, the TATA box, and the MRE II site in the IL-6 promoter; although MRE I and a GR-binding site between -201 and -210 in IL-6 both lacked a discernible inverted repeat motif, their sequences showed considerable similarity with negative GRE sequences in other Dex-repressed genes. Surprisingly, chimeric genes containing MRE II, which lacks a recognizable GACGTCA cyclic AMP- and phorbol ester-responsive motif, were strongly induced by both phorbol ester and forskolin, suggesting that MRE II (ACATTGCACAATCT) may be the prototype of a novel cyclic AMP- and phorbol ester-responsive element. Taken together, these observations suggest that ligand-activated GR represses the IL-6 gene by occlusion not only of the inducible IL-6 MRE enhancer region but also of the basal IL-6 promoter elements. PMID- 2233716 TI - Functional analysis of c-Myb protein in T-lymphocytic cell lines shows that it trans-activates the c-myc promoter. AB - The function of c-Myb protein was revealed by transfecting an expression vector containing the entire c-Myb protein-coding sequence into the murine CTLL-2 T-cell line. Expressions of high levels of c-Myb protein did not alter the expression of several T-cell markers, c-fos mRNA expression, responses to interleukin-2, and growth characteristics of these cells. Interestingly, expression of the c-myc gene was drastically increased in this clone. Further, the c-myb expression plasmid, but not a frameshift mutant of c-myb, enhanced the expression of a hybrid construct of c-myc promoter linked to a reporter gene by 8- to 14-fold. These results demonstrate a role of c-Myb protein in c-myc gene expression. PMID- 2233717 TI - p53 functions as a cell cycle control protein in osteosarcomas. AB - Mutations in the p53 gene have been associated with a wide range of human tumors, including osteosarcomas. Although it has been shown that wild-type p53 can block the ability of E1a and ras to cotransform primary rodent cells, it is poorly understood why inactivation of the p53 gene is important for tumor formation. We show that overexpression of the gene encoding wild-type p53 blocks the growth of osteosarcoma cells. The growth arrest was determined to be due to an inability of the transfected cells to progress into S phase. This suggests that the role of the p53 gene as an antioncogene may be in controlling the cell cycle in a fashion analogous to the check-point control genes in Saccharomyces cerevisiae. PMID- 2233718 TI - In vitro analysis of a transcription termination site for RNA polymerase II. AB - Transcription from the adenovirus major late (ML) promoter has previously been shown to pause or terminate prematurely in vivo and in vitro at a site within the first intron of the major late transcription unit. We are studying the mechanism of elongation arrest at this site in vitro to define the DNA sequences and proteins that determine the elongation behavior of RNA polymerase II. Our assay system consists of a nuclear extract prepared from cultured human cells. With standard reaction conditions, termination is not observed downstream of the ML promoter. However, in the presence of Sarkosyl, up to 80% of the transcripts terminate 186 nucleotides downstream of the start site. Using this assay, we showed that the DNA sequences required to promote maximal levels of termination downstream of the ML promoter reside within a 65-base-pair region and function in an orientation-dependent manner. To test whether elongation complexes from the ML promoter were functionally homogeneous, we determined the termination efficiency at each of two termination sites placed in tandem. We found that the behavior of the elongation complexes was different at these sites, with termination being greater at the downstream site over a wide range of Sarkosyl concentrations. This result ruled out a model in which the polymerases that read through the first site were stably modified to antiterminate. We also demonstrated that the ability of the elongation complexes to respond to the ML termination site was promoter specific, as the site did not function efficiently downstream of a heterologous promoter. Taken together, the results presented here are not consistent with the simplest class of models that have been proposed previously for the mechanism of Sarkosyl-induced termination. PMID- 2233719 TI - A novel immediate-early response gene of endothelium is induced by cytokines and encodes a secreted protein. AB - We have previously described the cloning of a group of novel cellular immediate early response genes whose expression in human umbilical vein endothelial cells is induced by tumor necrosis factor alpha in the presence of cycloheximide. These genes are likely to participate in mediating the response of the vascular endothelium to proinflammatory cytokines. In this study, we further characterized one of these novel gene products named B61. Sequence analysis of cDNA clones encoding B61 revealed that its protein product has no significant homology to previously described proteins. Southern analysis suggested that B61 is an evolutionarily conserved single-copy gene. B61 is primarily a hydrophilic molecule but contains both a hydrophobic N-terminal and a hydrophobic C-terminal region. The N-terminal region is typical of a signal peptide, which is consistent with the secreted nature of the protein. The mature form of the predicted protein consists of 187 amino acid residues and has a molecular weight of 22,000. Immunoprecipitation of metabolically labeled human umbilical vein endothelial cell preparations revealed that B61 is a 25-kilodalton secreted protein which is markedly induced by tumor necrosis factor. PMID- 2233720 TI - Repair and recombination of X-irradiated plasmids in Xenopus laevis oocytes. AB - Plasmid DNA substrates were X-irradiated and injected into the nuclei of Xenopus laevis oocytes. After incubation for 20 h, DNA was recovered from the oocytes and analyzed simultaneously for repair and for intermolecular homologous recombination by electrophoresis and bacterial transformation. Oocyte-mediated repair of DNA strand breaks was observed with both methods. Using a repair deficient mutant Escherichia coli strain and its repair-proficient parent as hosts for the transformation assay, we also demonstrated that oocytes repaired oxidative-type DNA base damage induced by X-rays. X-irradiation of a circular DNA stimulated its potential to recombine with a homologous linear partner. Recombination products were detected directly by Southern blot hybridization and as bacterial transformant clones expressing two antibiotic resistance markers originally carried separately on the two substrates. The increase in recombination was dependent on X-ray dose. There is some suggestion that lesions other than double-strand breaks contribute to the stimulation of oocyte-mediated homologous recombination. In summary, oocytes have considerable capacity to repair X-ray-induced damage, and some X-ray lesions stimulate homologous recombination in these cells. PMID- 2233721 TI - Structure and evolution of the U2 small nuclear RNA multigene family in primates: gene amplification under natural selection? AB - The organization of U2 genes was compared in apes, Old World monkeys, and the prosimian galago. In humans and all apes (gibbon, orangutan, gorilla, and chimpanzee), the U2 genes were organized as a tandem repeat of a 6-kb element; however, the restriction maps of the 6-kb elements in these divergent species differed slightly, demonstrating that mechanisms must exist for maintaining sequence homogeneity within this tandem array. In Old World monkeys, the U2 genes were organized as a tandem repeat of an 11-kb element; the restriction maps of the 11-kb elements in baboon and two closely related macaques, bonnet and rhesus monkeys, also differed slightly, confirming that efficient sequence homogenization is an intrinsic property of the U2 tandem array. Interestingly, the 11-kb monkey repeat unit differed from the 6-kb hominid repeat unit by a 5-kb block of monkey-specific sequence. Finally, we found that the U2 genes of the prosimian galago were dispersed rather than tandemly repeated, suggesting that the hominid and Old World monkey U2 tandem arrays resulted from independent amplifications of a common ancestral U2 gene. Alternatively, the 5-kb monkey specific sequence could have been inserted into the 6-kb array or deleted from the 11-kb array soon after divergence of the hominid and Old World monkey lineages. PMID- 2233723 TI - An amino-terminal c-myc domain required for neoplastic transformation activates transcription. AB - The product of the c-myc proto-oncogene is a nuclear phosphoprotein whose normal cellular function has not yet been defined. c-Myc has a number of biochemical properties, however, that suggest that it may function as a potential regulator of gene transcription. Specifically, it is a nuclear DNA-binding protein with a short half-life, a high proline content, segments that are rich in glutamine and acidic residues, and a carboxyl-terminal oligomerization domain containing the leucine zipper and helix-loop-helix motifs that serve as oligomerization domains in known regulators of transcription, such as C/EBP, Jun, Fos, GCN4, MyoD, E12, and E47. In an effort to establish that c-Myc might regulate transcription in vivo, we sought to determine whether regions of the c-Myc protein could activate transcription in an in vitro system. We report here that fusion proteins in which segments of human c-Myc are linked to the DNA-binding domain of the yeast transcriptional activator GAL4 can activate transcription from a reporter gene linked to GAL4-binding sites. Three independent activation regions are located between amino acids 1 and 143, a region that has been shown to be required for neoplastic transformation of primary rat embryo cells in cooperation with a mutated ras gene. These results demonstrate that domains of the c-Myc protein can function to regulate transcription in a model system and suggest that alterations of Myc transcriptional regulatory function may lead to neoplastic transformation. PMID- 2233722 TI - The HXT2 gene of Saccharomyces cerevisiae is required for high-affinity glucose transport. AB - The HXT2 gene of the yeast Saccharomyces cerevisiae was identified on the basis of its ability to complement the defect in glucose transport of a snf3 mutant when present on the multicopy plasmid pSC2. Analysis of the DNA sequence of HXT2 revealed an open reading frame of 541 codons, capable of encoding a protein of Mr 59,840. The predicted protein displayed high sequence and structural homology to a large family of procaryotic and eucaryotic sugar transporters. These proteins have 12 highly hydrophobic regions that could form transmembrane domains; the spacing of these putative transmembrane domains is also highly conserved. Several amino acid motifs characteristic of this sugar transporter family are also present in the HXT2 protein. An hxt2 null mutant strain lacked a significant component of high-affinity glucose transport when under derepressing (low glucose) conditions. However, the hxt2 null mutation did not incur a major growth defect on glucose-containing media. Genetic and biochemical analyses suggest that wild-type levels of high-affinity glucose transport require the products of both the HXT2 and SNF3 genes; these genes are not linked. Low-stringency Southern blot analysis revealed a number of other sequences that cross-hybridize with HXT2, suggesting that S. cerevisiae possesses a large family of sugar transporter genes. PMID- 2233724 TI - A hypoxic consensus operator and a constitutive activation region regulate the ANB1 gene of Saccharomyces cerevisiae. AB - We have identified a consensus operator sequence, YYYATTGTTCTC, which mediates the repression imposed by the ROX1 factor upon the members of the hypoxic gene regulon, which includes ANB1, HEM13, COX5b, and CYC7. The members of the regulon were repressed with widely varying stringency, and the variation was correlated with the number and fidelity of operator sequences observed. ANB1 had two operators operating with unequal efficiency, each containing two copies of the operator sequence. Synthetic operator sequences introduced into an operator deletion were effective as monomers but much more so as dimers, consistent with cooperativity. The native operators both imposed ROX1 repression on the GAL1 gene, in either orientation, but the synthetic operators did not, indicating that the sequence context may be important. The repression and activation of ANB1 are independent spatially and functionally, since deletion of the operators did not reduce expression and since both the operator and activation regions functioned separately in the GAL1 UAS. The ANB1 UAS was constitutive, containing several elements distributed over a 300-bp region. There were two dT-rich segments, one of 51 bp and one of 165 bp, the latter capable of activating transcription by itself. Flanking segments containing GRF2 (REB1) and ABF1 (GF1) sites may contribute to activation but were not essential. The UAS showed a strongly preferred orientation. PMID- 2233725 TI - The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs. AB - The SIN3 gene (also known as SDI1) is a negative regulator of the yeast HO gene. Mutations in SIN3 suppress the requirement for the SWI5 activator for expression of the yeast HO gene and change the normal asymmetric pattern of HO expression in mother and daughter cells. Furthermore, the in vitro DNA-binding activity of several DNA-binding proteins is reduced in extracts prepared from sin3 mutants. We have cloned the SIN3 gene and determined that a haploid strain with a SIN3 gene disruption is viable. We determined the sequence of the SIN3 gene, which is predicted to encode a 175-kDa polypeptide with four paired amphipathic helix motifs. These motifs have been identified in the myc family of helix-loop-helix DNA-binding proteins and in the TPR family of regulatory proteins. The SIN3 transcript was mapped, and it was determined that the SIN3 transcript was absent in stationary-phase cells. Immunofluorescence microscopy with anti-SIN3 antibody demonstrated that SIN3 protein was present in nuclei. A comparison of restriction map and sequence data revealed that SIN3 is the same as regulatory genes UME4 and RPD1. PMID- 2233726 TI - Prenylation of mammalian Ras protein in Xenopus oocytes. AB - Ras protein requires an intermediate of the cholesterol biosynthetic pathway for posttranslational modification and membrane anchorage. This step is necessary for biological activity. Maturation of Xenopus laevis oocytes induced by an oncogenic human Ras protein can be inhibited by lovastatin or compactin, inhibitors of the synthesis of mevalonate, an intermediate of cholesterol biosynthesis. This inhibition can be overcome by mevalonic acid or farnesyl diphosphate, a cholesterol biosynthetic intermediate downstream of mevalonate, but not by squalene, an intermediate after farnesyl pyrophosphate in the pathway. This study supports the idea that in Xenopus oocytes, the Ras protein is modified by a farnesyl moiety or its derivative. Furthermore, an octapeptide with the sequence similar to the C-terminus of the c-H-ras protein inhibits the biological activity of Ras proteins in vivo, suggesting that it competes for the enzyme or enzymes responsible for transferring the isoprenoid moiety (prenylation) in the oocytes. This inhibition of Ras prenylation by the peptide was also observed in vitro, using both Saccharomyces cerevisiae and Xenopus oocyte extracts. These observations show that Xenopus oocytes provide a convenient in vivo system for studies of inhibitors of the posttranslational modification of the Ras protein, especially for inhibitors such as peptides that do not penetrate cell membranes. PMID- 2233727 TI - Promoter elements and erythroid cell nuclear factors that regulate alpha-globin gene transcription in vitro. AB - We have previously purified four factors (alpha-IRP, alpha-CP1, alpha-CP2, and NF E1) that interact with the promoter of the alpha-globin gene. One of these (NF E1) is a tissue-restricted factor that has recently been cloned. The binding sites of these factors identify DNA sequence elements that might mediate the tissue-specific and inducible transcription of the alpha-globin gene. This possibility was tested in a series of in vitro transcription experiments. An examination of 5' truncated templates and synthetic promoters constituted from individual factor-binding sites apposed to the alpha-TATAA box showed that the binding elements of three factors (alpha-CP1, alpha-IRP, and NF-E1) mediate four- to sixfold activation of transcription in vitro. In contrast, one element (alpha CP2) stimulated transcription less than twofold. The 5- to 10-fold stimulation of these latter templates upon addition of a DNA sequence affinity-purified factor suggests that alpha-CP2 is functionally limiting in nuclear extracts. Additional experiments further tested the effect of supplementing extracts with factors purified from erythroid cell nuclear extracts or, in the case of NF-E1, enriched from a bacterial cDNA expression system. Each factor tested stimulated transcription in vitro in a binding-site-dependent manner. Our results provide a comprehensive functional view of the murine alpha-globin promoter and suggest possible mechanisms for activation of alpha-globin gene transcription during induced differentiation of murine erythroleukemia cells. PMID- 2233728 TI - A phorbol ester-regulated ribonuclease system controlling transforming growth factor beta 1 gene expression in hematopoietic cells. AB - 12-Tetradecanoylphorbol-13-acetate (TPA)-induced differentiation of U937 promonocytes leads to a 30-fold increase in transforming growth factor beta 1 (TGF-beta 1) gene expression, and this effect results from a stabilized mRNA. Similar up-regulation was detected in TPA-treated K562 erythroblasts but was absent from cell lines that do not differentiate in response to TPA. Related studies in vitro showed that postnuclear extracts of U937 promonocytes contain a ribonuclease system that degrades TGF-beta 1 mRNA selectively and that this system is completely blocked by prior treatment of the cells with TPA. These data identify a new mechanism for regulating TGF-beta 1 mRNA levels and allow us to establish the overall basis for control of TGF-beta 1 gene expression by activation of protein kinase C. Our results also provide a new basis for understanding the long-term up-regulation of TGF-beta 1 gene expression that can accompany hematopoietic cell differentiation. PMID- 2233729 TI - Analysis of the mouse Dhfr/Rep-3 major promoter region by using linker-scanning and internal deletion mutations and DNase I footprinting. AB - The mouse dihydrofolate reductase (Dhfr) promoter region is buried within a CpG island (a region rich in unmethylated CpG dinucleotides), has a high G+C content, and lacks CAAT and TATA elements. The region contains four 48-bp repeats, each of which contains an Sp1-binding site. Another gene, Rep-3 (formerly designated Rep 1), shares the same general promoter region with Dhfr, being transcribed in the direction opposite that of Dhfr. Both genes appear to be housekeeping genes and are expressed at relatively low levels in all tissues. The 5' termini of the major Dhfr transcripts are separated from the 5' termini of the Rep-3 transcripts by approximately 140 bp. This curious structural arrangement suggested that the two genes might share common regulatory elements. To investigate the promoter sequences driving bidirectional transcription, a series of promoter mutations was constructed. These mutations were assayed by a replicating minigene system and by promoter fusions to the chloramphenicol acetyltransferase gene. Linker-scanning mutations that spanned the four repeats produced a variety of mRNA transcript phenotypes. The effects were primarily quantitative, generally reducing the abundance of transcripts for one or both genes. Some mutations affected Dhfr in a qualitative manner, such as by changing the startpoint of one of the major Dhfr transcripts or changing the relative abundance of the two major Dhfr transcripts. Additionally, protein transcription factors that bind to sequences in the mouse Dhfr/Rep-3 major promoter region, potentially affecting expression of either or both genes, were investigated by DNase I footprinting. The results indicate that multiple protein-DNA interactions occur in this region, reflecting potentially complex transcriptional control mechanisms that might modulate expression of either or both genes under different physiological conditions. PMID- 2233730 TI - Structural and functional dissection of Sec62p, a membrane-bound component of the yeast endoplasmic reticulum protein import machinery. AB - SEC62 is required for the import of secretory protein precursors into the endoplasmic reticulum (ER) of Saccharomyces cerevisiae. The DNA sequence of SEC62 predicts a 32-kDa polypeptide with two potential membrane-spanning segments. Two antisera directed against different portions of the SEC62 coding region specifically detected a 30-kDa polypeptide in cell extracts. A combination of subcellular fractionation, detergent and alkali extraction, and indirect immunofluorescence studies indicated that Sec62p is intimately associated with the ER membrane. Protease digestion of intact microsomes and analysis of the oligosaccharide content of a set of Sec62p-invertase hybrid proteins suggested that Sec62p spans the ER membrane twice, displaying hydrophilic amino- and carboxy-terminal domains towards the cytosol. Sec62p-invertase hybrid proteins that lack the Sec62p C terminus failed to complement the sec62-l mutation and dramatically inhibited the growth of sec62-l cells at a normally permissive temperature. The inhibitory action of toxic Sec62p-invertase hybrids was partially counteracted by the overexpression of Sec63p. Taken together, these data suggest that the C-terminal domain of Sec62p performs an essential function and that the N-terminal domain associates with other components of the translocation machinery, including Sec63p. PMID- 2233731 TI - Manipulations of cholinesterase gene expression modulate murine megakaryocytopoiesis in vitro. AB - Megakaryocytopoiesis was selectively inhibited in cultured murine bone marrow cells by a 15-mer oligodeoxynucleotide complementary to the initiator AUG region in butyrylcholinesterase mRNA. Furthermore, conditioned medium from Xenopus oocytes producing recombinant butyrylcholinesterase stimulated megakaryocytopoiesis. These observations implicate butyrylcholinesterase in megakaryocytopoiesis and suggest application of oligodeoxynucleotides for modulating bone marrow development. PMID- 2233732 TI - Alternatively spliced platelet-derived growth factor A-chain transcripts are not tumor specific but encode normal cellular proteins. AB - Two platelet-derived growth factor A-chain proteins, termed short and long A chains, are generated as a result of alternative mRNA splicing of exon 6 of the A chain gene. S1 nuclease mapping and polymerase chain reaction analyses demonstrate that both short and long A-chain transcripts are expressed in a variety of normal tissues. In addition, immunohistochemical localization of long A-chain protein reveals a cellular distribution identical to that observed with platelet-derived growth factor heteroserum. PMID- 2233733 TI - Chromosome organization of the protozoan Trypanosoma brucei. AB - The genome of the protozoan Trypanosoma brucei is known to be diploid. Karyotype analysis has, however, failed to identify homologous chromosomes. Having refined the technique for separating trypanosome chromosomes (L. H. T. Van der Ploeg, C. L. Smith, R. I. Polvere, and K. Gottesdiener, Nucleic Acids Res. 17:3217-3227, 1989), we can now provide evidence for the presence of homologous chromosomes. By determining the chromosomal location of different genetic markers, most of the chromosomes (14, excluding the minichromosomes), could be organized into seven chromosome pairs. In most instances, the putative homologs of a pair differed in size by about 20%. Restriction enzyme analysis of chromosome-sized DNA showed that these chromosome pairs contained large stretches of homologous DNA sequences. From these data, we infer that the chromosome pairs represent homologs. The identification of homologous chromosomes gives valuable insight into the organization of the trypanosome genome, will facilitate the genetic analysis of T. brucei, and suggests the presence of haploid gametes. PMID- 2233734 TI - The repeated sequence CATT(A/T) is required for granulocyte-macrophage colony stimulating factor promoter activity. AB - The hematopoietic growth factor GM-CSF (granulocyte-macrophage colony-stimulating factor) is expressed by activated but not resting T lymphocytes. Previously, we localized GM-CSF-inducible promoter activity to a 90-bp region of GM-CSF 5' flanking sequences extending from bp -53 to +37. To more precisely identify the GM-CSF DNA sequences required for inducible promoter activity in T lymphocytes, we have performed mutagenesis within a region of GM-CSF 5'-flanking sequences (bp -57 to -24) that contains the repeated sequence CATT(A/T). Mutations that do not alter the repeated CATT(A/T) sequence do not eliminate inducible promoter activity, whereas mutation or deletion of either of the CATT(A/T) repeats eliminates all inducible promoter activity in T-cell lines and in primary human T lymphocytes. Thus, both copies of the direct repeat CATT(A/T) are required for mitogen-inducible expression of GM-CSF in T cells. PMID- 2233735 TI - Molecular characterization of SerH3, a Tetrahymena thermophila gene encoding a temperature-regulated surface antigen. AB - The DNA sequences of a cDNA clone and the macronuclear genomic fragment corresponding to the functional copy of the SerH3 surface antigen gene of Tetrahymena thermophila were determined. Primer extension and nuclease protection assays show that the SerH3 transcription unit is 1,425 nucleotides long and contains no introns. The predicted polypeptide encoded by the SerH3 gene has a molecular mass of 44,415 daltons; one-third of its 439 residues are either cysteine, serine, or threonine. The central half of the polypeptide consists of three homologous domains in tandem array; within these domains, the cysteine, proline, and tryptophan residues occur in highly regular patterns. PMID- 2233736 TI - Functional analysis of a duplicated linked pair of ribosomal protein genes in Saccharomyces cerevisiae. AB - Ribosomal protein genes RP28 and S16A (RP55) are closely linked. Another set of this pair of genes exists in the genome (copy 2), genetically unlinked to copy 1. By using gene replacement techniques, we have shown that RP28 from copy 1 is required for vegetative growth and that the cells need S16A from copy 2 to achieve maximum growth rate. PMID- 2233737 TI - An abnormal splice donor site in one allele of the thyroid peroxidase gene in FRTL5 rat thyroid cells introduces a premature stop codon: association with the absence of functional enzymatic activity. AB - Low stringency screening of an FRTL5 cDNA library with a human thyroid peroxidase (TPO) cDNA probe yielded two different types of TPO cDNA clones. One type contained the full-length structural gene, but there was an A at the first nucleotide of an intronic splice donor site that leads to alternate splicing, with the retention of part of an intron. This 54-basepair retained intron fragment contains a premature inframe stop codon that would truncate the protein at its carboxyl-terminus by 71% with the loss of enzymatic activity. The second type of TPO cDNA does not contain the retained intron fragment and premature stop codon, but it is not full-length and lacks 580-680 basepairs at its 5' end. However, Northern blot analysis reveals only full-length copies (3.2 kilobases) of TPO mRNA in FRTL5 cells, and this 5' truncation is, therefore, an artifact of library construction. The relative proportions of the two types of TPO mRNA in FRTL5 cells was determined by the polymerase chain reaction, using as template single stranded cDNA generated by reverse transcription of FRTL5 mRNA. Slightly more than half of the TPO mRNA in the FRTL5 cells represented the form with the abnormal splice donor site. The relative proportions of the two TPO mRNA forms was not influenced by TSH stimulation of the FRTL5 cells, and the proportion remained unaltered even after the FRTL5 cells were subcloned by limiting dilution. At the genomic level, we used allele-specific oligonucleotides for the mutant and normal forms of TPO, and found FRTL5 cells to have both normal and abnormal TPO alleles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233738 TI - Glucagon gene 3'-flanking sequences direct formation of proglucagon messenger RNA 3'-ends in islet and nonislet cells lines. AB - Glucagon and the glucagon-like peptides are encoded within a larger precursor, proglucagon. Transcription of the glucagon gene in pancreas, intestine, and brain gives rise to identical proglucagon mRNA transcripts, after which tissue-specific post-translational processing produces different profiles of proglucagon-derived peptides in each tissue. The importance of glucagon gene 3'-untranslated and 3' flanking sequences in the control of glucagon mRNA production was studied by transfecting a series of 3'-deleted glucagon genes into fibroblast and islet cell lines. Glucagon genes containing 2 kilobases of 3'-flanking sequences gave rise to accurately processed mRNA transcripts in both baby hamster kidney fibroblasts and InR1-G9 islet cell lines. Deletion of all but 50 basepairs of 3'-flanking sequence had no effect on glucagon mRNA 3'-end formation. In contrast, additional deletion of 3'-flanking and 3'-untranslated sequences resulted in the production of read-through mRNA transcripts with aberrant 3'-ends. The results of these studies define a 50-basepair region in the 3'-flanking sequence of the glucagon gene important for the accurate processing of proglucagon mRNA transcripts. PMID- 2233739 TI - High concentrations of estrogen stabilize vitellogenin mRNA against cytoplasmic degradation but physiological concentrations do not. AB - Using DNA excess filter hybridization to pulse-labeled cellular RNA, we examined the stability of vitellogenin mRNA in Xenopus liver in relation to estrogen concentration. We showed that pharmacological concentrations of estrogen stabilize vitellogenin mRNA against degradation but that physiological concentrations do not. We concluded that there is little foundation for the common belief that estrogen stabilizes vitellogenin mRNA in normal liver cells and that such stabilization contributes to the normal expression of vitellogenin genes. We also discuss the importance of steroid concentration in other contexts, and show that the widespread tendency to use artificially high concentrations may lead to questionable conclusions. PMID- 2233740 TI - Developmental changes in levels of proopiomelanocortin intron A-containing heterogeneous nuclear RNA and mature messenger RNA in the anterior and neurointermediate lobes of the rat pituitary. AB - The POMC cells of the rat pituitary undergo dynamic phenotypic changes during differentiation. Here we have determined that alterations in the relative levels of a POMC precursor RNA species and POMC mRNA occur during development and may represent another level at which the POMC phenotype is developmentally regulated. We performed solution hybridization/nuclease protection assays using a POMC exon 1/intron A splice junction probe to quantitate levels of both intron A-containing POMC heterogeneous nuclear (hnRNA) and fully processed POMC mRNA in separated anterior and neurointermediate lobes of the fetal, neonatal, and adult pituitary. The levels of POMC hnRNA per anterior lobe increased 7-fold from embryonic day 15 to adulthood (0.022 to 0.159 fmol/lobe), while POMC mRNA levels increased 121 fold (0.15 to 18.2 fmol/lobe). POMC hnRNA levels per neurointermediate lobe increased 23-fold from embryonic day 18 to adulthood (0.024 to 0.54 fmol/lobe), while POMC mRNA levels increased 69-fold (0.65 to 44.6 fmol/lobe). Thus, both anterior and neurointermediate lobes contain higher relative abundances of POMC hnRNA compared to mRNA during early development. These subsequently decrease (from 1:7 to 1: approximately 110 in the anterior lobe and from 1:27 to 1:83 in the intermediate lobe over the ages examined) as the levels of POMC mRNA in both anterior and neurointermediate lobe increase at a greater rate than POMC hnRNA as development progresses. These results provide the first measurements of POMC mRNA and hnRNA levels during ontogeny and suggest that there may be a developmental change in the regulation of POMC primary transcript processing. PMID- 2233741 TI - Progestin regulation of estrogen receptor messenger RNA in human breast cancer cells. AB - Progestin antagonism of estrogen action is thought to be due, at least in part, to progestin down-regulation of the estrogen receptor (ER). The molecular mechanisms subserving this effect, and the functional consequences in terms of target cell sensitivity to estrogens, are poorly understood. The present study was undertaken to address these issues with particular emphasis on progestin regulation of ER gene expression at the mRNA level. The T-47D human breast cancer cell line was treated with the synthetic progestin, ORG 2058, and the resultant changes in ER mRNA and ER levels determined by Northern analysis and radioligand binding, respectively. Treatment of T-47D cells with ORG 2058 resulted in rapid down-regulation of ER mRNA levels to a nadir of 35-40% of control by 6 h. This fall in ER mRNA levels was accompanied by a slower but more sustained fall in ER binding to a nadir of 20% of control at 24 h. Between 12 and 24 h ER mRNA levels recovered partially while ER ligand binding continued to fall. At 48 h both ER mRNA and ER concentrations remained depressed, although the latter to a greater extent. ER mRNA half-life was determined by [3H]uridine incorporation to be approximately 60 min and was unaffected by progestin treatment during the early rapid phase of ER mRNA down-regulation. These data demonstrate that progestins cause rapid down-regulation of the ER mRNA and suggest that during the early rapid phase of this effect, reduced transcription of the ER gene rather than altered ER mRNA half-life mediate this effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233742 TI - Identification and characterization of two upstream elements that regulate adrenocortical expression of steroid 11 beta-hydroxylase. AB - We have studied the mechanisms that regulate the expression of the mouse gene encoding steroid 11 beta-hydroxylase (11 beta-OHase), a steroidogenic cytochrome P450 enzyme that is expressed only in the adrenal cortex. DNase I footprinting and gel-mobility shift analyses revealed potential regulatory elements at -370 and -310 in the 11 beta-OHase promoter region. To determine the contributions of these elements to expression, we altered their sequences by site-selected mutagenesis and studied promoter activity after transfection into Y1 mouse adrenocortical tumor cells. Mutation of either element markedly decreased basal promoter activity but did not affect the response to treatment with 8-bromo cAMP. These experiments thus document the functional roles of these elements, within the context of the intact promoter, in constitutive expression of 11 beta-OHase. Moreover, addition of either of these elements to p-40GH, a 5'-deletion plasmid containing 11 beta-OHase sequences from -40 to +8 upstream of a growth hormone reporter gene, significantly increased promoter activity but did not confer cAMP responsiveness. Finally, increased expression was seen after transfection of Y1 derivatives deficient in cAMP-dependent protein kinase, indicating that neither element required cAMP-dependent protein kinase activity. These studies thus define two regulatory elements that play important roles in 11 beta-OHase expression. PMID- 2233743 TI - Identification of an up-stream promoter of the human parathyroid hormone-related peptide gene. AB - Previous evidence has suggested that the human PTH-related peptide (PTHRP) gene uses two promoters, one a short down-stream element lying immediately between two 5' exons (1 and 2) and a second lying in an unknown up-stream location. We approached identification of the up-stream element in three steps. First, Northern analysis carried out using progressively 5' fragments of the gene as probes identified a candidate region some 2.5 kilobases up-stream of exon 1. Second, a battery of overlapping 5' cRNA probes was used in RNase protection experiments to identify two previously unrecognized exons, 212 and 93 basepairs in length (termed exons 1A and 1B to distinguish them from the previously designated exon 1, which was termed exon 1C). Third, primer extension experiments were performed with oligonucleotides complementary to each of the 5' exonic sequences. These experiments identified a transcription start site up-stream of exon 1A and also demonstrated that the 5' exons of the PTHRP gene could be spliced together in several combinations. The up-stream promoter element contains a TATA box, but does not otherwise resemble the down-stream PTHRP gene promoter or the PTH gene promoter. We conclude that the human PTHRP gene contains eight exons spanning more than 15 kilobases of genomic DNA, with promoter elements lying immediately up-stream of exons 1A and 2. The identification of these elements will permit functional analysis of their roles in mediating tissue- and tumor-specific PTHRP gene expression. PMID- 2233744 TI - Molecular modeling of residues 38-57 of the beta-subunit of human lutropin. AB - Several regions on both the alpha- and beta-subunits of human LH comprise the receptor-binding domain of the hormone. One of these, a disulfide loop peptide containing residues 38-57 on the beta-subunit, also stimulated steroidogenesis in rat Leydig cells. Circular dichroism analysis and a Schiffer-Edmundson helical wheel projection of beta-(38-57) revealed the possibility of an amphipathic alpha helical structure through its N-terminal region. Secondary structure prediction algorithms do not predict alpha-helix in beta-(38-57), but, rather, suggest a sheet-coil-sheet topology. Homology searches between this peptide and proteins with known structure revealed that the two best matches are with prealbumin-(10 30) and melittin-(1-26). Based on hydrophobic moment calculations, we suggest that beta-(38-57) more closely resembles melittin, a known example of an amphipathic helix. Molecular models were constructed that included an alpha-helix between Pro-39 and Pro-50 producing a hydrophilic face involving Thr-40, Arg-43, and Gin-46. Loop closure was performed either visually or by an incremental minimization procedure, using distance constraints to patch in a disulfide bond. Molecular dynamics at 300, 360, and 1000 K were used to explore the local conformational space, and dynamic structures were minimized. The most reasonable structures were found with the 300 and 360 K simulations, with those at 360 K consistently producing structures with lower conformational energies. In each of these simulations, the N-terminus of the alpha-helix unraveled to form a reverse turn (predicted by the GOR algorithm) which include Cys-38, Pro-39, Thr-40, and Met-41. Simulations at 1000 K produced the most variation in structure, but these were deemed unreasonable. Although not all possible conformations were explored, several models were found that comply with the assumption of an amphipathic helix in the N-terminal half of the peptide. PMID- 2233745 TI - Diurnal pattern of proopiomelanocortin gene expression in the arcuate nucleus of proestrous, ovariectomized, and steroid-treated rats: a possible role in cyclic luteinizing hormone secretion. AB - Opiate peptides are thought to modulate the pattern of LH release in female rats. We tested the hypothesis that changes in proopiomelanocortin (POMC) gene expression occur in proestrous (PRO) and ovariectomized (OVX) steroid-treated rats which may explain their unique patterns of LH secretion. Using in situ hybridization, we examined whether diurnal changes in POMC gene expression occur in the arcuate nucleus. Four groups of rats were used in this study. 1) PRO rats were used after exhibiting at least two consecutive 4-day estrous cycles; 2) OVX rats were killed 9 days after ovariectomy; 3) estradiol (E2)-treated rats were OVX for 7 days and then treated for 2 days; and 4) E2-progesterone (P4)-treated rats were treated with E2 as described above, and on day 9 at 1030 h, P4 was administered. Rats were killed at 2300, 0300, 1000, 1300, 1500, 1800, or 2300 h, beginning on the evening of diestrous day 2 or day 8 after ovariectomy. POMC gene expression exhibited a diurnal rhythm on PRO. Levels of mRNA rose during the morning, peaked between 0300-1000 h, and decreased by 2300 h. In E2-treated rats, which exhibited a LH surge similar in timing to the PRO surge, POMC mRNA levels exhibited a diurnal rhythm strikingly similar to that observed in PRO animals. OVX abolished the rhythm; however, average POMC mRNA levels across the 24-h period were not significantly different from those in PRO or E2-treated rats. P4 treatment increased POMC mRNA levels by 2300 h compared to those in all other experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233746 TI - Expression of human 21-hydroxylase (P450c21) in bacterial and mammalian cells: a system to characterize normal and mutant enzymes. AB - Cytochrome P450c21 (steroid 21-hydroxylase) is a key enzyme in the synthesis of cortisol, whose deficiency is the cause of a common genetic disease, congenital adrenal hyperplasia. We have expressed P450c21 (steroid 21-hydroxylase) in E. coli and mammalian cells. In E. coli, P450c21 cDNA was cloned into a T7 expression vector to produce a large amount of P450c21 fusion protein, which enabled antiserum production. In mammalian cells, a plasmid containing full length P450c21 cDNA (phc21) was constructed and transfected into COS-1 cells to produce active P450c21, which was detected by immunoblotting and 21-hydroxylase activity assay. This system was used to assay mutations involved in the disease. Ile172 of phc21 corresponding to the site of mutation in some cases of the disease was mutagenized to become Asn, Leu, His, or Gln. Mutant as well as normal P450c21 was produced when their cDNAs were transfected into COS-1 cells. The mutant proteins, however, had greatly reduced 21-hydroxylase activities. Therefore, missense mutation at Ile172 resulted in inactivation of the enzyme, but not in repression of enzyme synthesis. The Leu for Ile substitution at amino acid 172 did not result in partial restoration of enzymatic activity, indicating that hydrophobicity at this residue may not play a role in its function. PMID- 2233747 TI - Alternative splicing produces messenger RNAs encoding insulin-like growth factor I prohormones that are differentially glycosylated in vitro. AB - Rat insulin-like growth factor-I (IGF-I) cDNA sequences predict two prohormones that differ in the carboxy-terminal extension peptide (E-peptide) as a result of the inclusion or exclusion of the 52-basepair exon 4 sequence. In the absence of exon 4, the sequence codes for the IGF-Ia prohormone, whose E region contains two potential N-glycosylation sites. With differential splicing and the inclusion of exon 4, the resultant mRNA codes for IGF-Ib, with a longer E-region sequence. In addition, as a consequence of a frame shift, both potential glycosylation sites are lost in the IGF-Ib peptide. We used an in vitro translation system supplemented with canine pancreatic microsomal membranes to analyze cotranslational processing of the IGF-I propeptides. We have demonstrated that IGF-Ia prohormone, which contains two potential N-glycosylation sites in the E region, can be N-glycosylated in vitro, and that both glycosylation sites are probably used. As expected, the IGF-Ib preprohormone is processed by microsomes, but is not glycosylated. PMID- 2233748 TI - Cellular localization of ovarian proopiomelanocortin messenger RNA during follicular and luteal development in the rat. AB - Opioid peptides are expressed in the reproductive system and have been reported to regulate reproductive function. The present study used in situ hybridization to selectively localize ovarian cells containing high levels of proopiomelanocortin (POMC) mRNA, an opioid precursor, during different stages of ovarian development. Prepubertal rats were primed with PMSG to stimulate follicular development, followed by hCG to induce ovulation. Treatment groups consisted of control (no treatment), PMSG (2 days post-PMSG), 1 day corpus luteum (CL; 1 day post-hCG), and 8 day CL (8 days post-hCG). POMC mRNA-containing cells were present in antral follicles, CL, and the interstitial compartment. With gonadotropin treatment, the percentage of follicles containing heavily labeled cells increased in the PMSG and 1 day CL groups. The number of POMC mRNA containing cells per follicle also increased in the 1 day CL group. In the CL, no difference was observed in the percentage of CL exhibiting labeled cells between the 1 day CL and 8 day CL groups; however, more labeled luteal cells per CL were present in the 1 day CL group. A marked increase in POMC mRNA-containing cells was observed in the interstitial compartment of the 1 day CL group. These results indicate that the number of POMC mRNA-containing cells increases with follicular development and CL formation; however, the ovarian distribution suggests that the labeled cells could be nonendocrine cells, possibly white blood cells. The in situ hybridization findings are indicative of low total concentrations of ovarian POMC mRNA, suggesting mainly an autocrine or paracrine role for POMC or POMC derived peptides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233749 TI - Tissue specificity of the hormonal response in sex accessory tissues is associated with nuclear matrix protein patterns. AB - The DNA of interphase nuclei have very specific three-dimensional organizations that are different in different cell types, and it is possible that this varying DNA organization is responsible for the tissue specificity of gene expression. The nuclear matrix organizes the three-dimensional structure of the DNA and is believed to be involved in the control of gene expression. This study compares the nuclear structural proteins between two sex accessory tissues in the same animal responding to the same androgen stimulation by the differential expression of major tissue-specific secretory proteins. We demonstrate here that the nuclear matrix is tissue specific in the rat ventral prostate and seminal vesicle, and undergoes characteristic alterations in its protein composition upon androgen withdrawal. Three types of nuclear matrix proteins were observed: 1) nuclear matrix proteins that are different and tissue specific in the rat ventral prostate and seminal vesicle, 2) a set of nuclear matrix proteins that either appear or disappear upon androgen withdrawal, and 3) a set of proteins that are common to both the ventral prostate and seminal vesicle and do not change with the hormonal state of the animal. Since the nuclear matrix is known to bind androgen receptors in a tissue- and steroid-specific manner, we propose that the tissue specificity of the nuclear matrix arranges the DNA in a unique conformation, which may be involved in the specific interaction of transcription factors with DNA sequences, resulting in tissue-specific patterns of secretory protein expression. PMID- 2233750 TI - Selective expression and developmental regulation of the ancestral rat insulin II gene in fetal liver. AB - Previous studies have indicated that high levels of insulin synthesis occur in the yolk sac of fetal rats. Because the yolk sac is an early site for synthesis of several tissue-specific proteins synthesized by liver later in development, these studies were performed to determine whether insulin gene expression also occurs in fetal liver. To this purpose, liver RNA obtained on consecutive days of rat fetal development from embryo day (E) 13 to E21 was evaluated for the presence of insulin or insulin-like mRNA species using Northern hybridization with a uniformly labelled rat insulin II genomic antisense RNA probe. Two species were detected. The larger was approximately 2.4 kilobases in length, was very low in abundance, and was present only during the earliest days studied (E13-15). The second species was approximately 720 bases in length, increased in abundance between days E13-16, and decreased between days E16-21. Maximum abundance of this mRNA was 0.3 pg/microgram total liver RNA, or 1/10th to 1/20th the abundance of total insulin mRNA in adult rat pancreas. Sequencing of multiple cloned products of E15 rat liver cDNA amplified by polymerase chain reaction using insulin I or II gene-specific primers indicated that the bands detected on Northern hybridization were (ancestral) rat insulin II gene transcripts. Analysis of products of polymerase chain reactions also indicated that the duplicated rat insulin I gene was not expressed in fetal liver. The content of insulin mRNA in fetal liver is sufficient to suggest that the liver may be a significant source for insulin at specific times during fetal development. PMID- 2233751 TI - Association of proenkephalin transcripts with polyribosomes in the heart. AB - Previous results have shown that the relative abundance of proenkephalin mRNA in the rat heart is comparable to the levels found in the brain; however, the extractable enkephalin-containing peptide levels are much lower in the heart. This lack of correspondence between the levels of transcript and peptide could arise from either the inefficient translation of proenkephalin transcripts or the translation of proenkephalin transcripts into peptides that are rapidly secreted or degraded. To distinguish between these possibilities, the translational status of proenkephalin mRNA in the rat heart was established by Northern blot analysis of sucrose density gradient-sedimented polysomal fractions and compared to the striatum, which is known to efficiently translate proenkephalin transcripts. In both tissues, we detected 1.5-kilobase transcripts, but an additional larger transcript of approximately 3.6 kilobases was detected in the heart. Both transcripts were associated primarily with polyribosomes, suggesting active translation of proenkephalin mRNA in the rat heart. RIA of the culture media and extracts from primary cultures of neonatal rat cardiomyocytes indicated the presence of immunoreactive Met-enkephalin-Arg6-Phe7, which was stimulated by 8-(4 chlorophenylthio)cAMP. These results suggest that proenkephalin transcripts are translated in the heart and that detectable levels of immunoreactive Met enkephalin-Arg6-Phe7 are present in the media and cell extracts of primary cultures of neonatal rat cardiomyocytes. PMID- 2233752 TI - Lipoprotein lipase gene expression in rat adipocytes is regulated by isoproterenol and insulin through different mechanisms. AB - Lipoprotein lipase (LPL) is highly regulated by catecholamines and insulin in adipocytes. Isoproterenol, a beta-adrenergic agonist, decreases LPL enzyme activity, whereas insulin increases LPL activity. We have isolated an 868 basepair rat LPL cDNA clone to assess hormone-mediated changes in LPL steady state mRNA levels and LPL gene transcription rates in adipocytes. Northern blot analysis of isoproterenol-treated (10(-6) M) adipocytes showed that LPL steady state mRNA decreased by 15 min. Nuclear run-on transcription assays in isoproterenol-treated cells indicated that LPL gene transcription was also decreased at 15 min compared to that in control cells. Conversely, insulin (6.7 x 10(-8) M) mediated an increase in LPL steady state mRNA in treated adipocytes, yet LPL gene transcription was not different from that in control cells. Thus, the isoproterenol-mediated decrease in LPL enzyme activity and steady state mRNA levels in adipocytes is associated with decreases in LPL gene transcription. Insulin, which does not affect LPL gene transcription, increases LPL enzyme activity and steady state mRNA levels. The effect of insulin on LPL mRNA is probably due to insulin-induced changes in mRNA stability. PMID- 2233754 TI - Immunoassays employing substituted ammonium compounds other than neuromuscular blocking drugs to increase the detection of IgE antibodies to these drugs. AB - Subjects who experience life-threatening anaphylactic reactions to neuromuscular blocking drugs frequently have serum IgE antibodies that react with substituted ammonium groups on the drugs. Failure to detect drug-reactive antibodies may be due to the nature of the drug-solid support used for testing sera. With this in mind, solid phases of some selected compounds containing substituted ammonium groups, in particular triethylamine and morphine, were prepared and used to screen sera in an attempt to increase the frequency of detection of IgE antibodies complementary to tertiary and/or quaternary ammonium groups. For subjects who experienced an anaphylactic reaction to succinylcholine or gallamine, use of the supplementary assays increased the frequency of detection from 83 to 100%. For d-tubocurarine and alcuronium, detections increased from 92 to 100% and from 67 to 88%, respectively. Molecular models revealed a clear structural similarity between the conformations of the trialkylammonium groups on one face of the molecules of morphine and d-tubocurarine. PMID- 2233753 TI - Comparison of three related methods to select T cell-presented sequences of protein antigens. AB - A comparison of three methods to predict T cell-presented sequences within antigenic proteins led to the view that recurrent hydrophobic residues might nucleate excised peptides as alpha-helices against hydrophobic surfaces. Such helices could be protease-protected structures on their way to desetope binding. The compared methods were: the amphipathicity algorithm of DeLisi and Berzofsky [Proc. natn. Acad. Sci. U.S.A. 82, 7048-7052. (1985)] as modified by Margalit et al. [J. Immun. 138, 2213-2229. (1987)] the strip of-helix hydrophobicity algorithm (SOHHA) of Stille et al. [Molec. Immun. 24, 1021-1027. (1987)] and the motifs algorithm of Rothbard and Taylor [EMBO J. 7, 93-100. (1988)]. Correct prediction was defined at two levels of stringency: (1) the predicted sequence overlapped the experimentally reported sequence when the ratio of the intersection of both to the union of both greater than or equal to 0.5 or (2) the sequences touched when there was a non-empty intersection of both sequences. We determined the sensitivity (correct predictions/number of reported T cell presented sequences) and efficiency (correct predictions/number of predictions) at each level of stringency. In terms of overlap, the SOHHA was more sensitive (0.43) than the amphipathicity (0.29) (not significant) and motifs (0.0, 0.0) (p less than 0.05) predictions and more efficient (0.35) than the amphipathicity (0.14) and motifs (0.0, 0.0) predictions. At the less stringent criterion touching, the amphipathicity method (0.71) was as sensitive as motif Rothbard-4 (0.79) and more sensitive than SOHHA (0.57) and motif Rothbard-5 (0.43). At that criterion, the SOHHA was more efficient (0.47) than the amphipathicity (0.36) and motifs (0.25, 0.40) methods. We hypothesize that the comparability of these approaches reflected the common, predominant influence of recurrent hydrophobicity in their predictions. PMID- 2233755 TI - Isolation and characterization of a glycoprotein allergen, Art v II, from pollen of mugwort (Artemisia vulgaris L.). AB - A glycoprotein allergen, Art v II, was isolated from pollen of mugwort by two different isolation procedures. Art v II-A was isolated by a combination of ion exchange chromatography on DEAE-Sepharose, affinity chromatography on Con A Sepharose and ion-exchange chromatography on Mono P. Art v II-B was isolated by a combination of preparative IEF in Ultrodex granulated gel, affinity chromatography on Con A-Sepharose and HPLC size exclusion on Ultropac TSK G2000SW. Art v II-A and Art v II-B were shown to be antigenically identical with the allergen we have formerly denoted Ag7. The MW of Art v II A/B was determined to be 34,000-38,000 by HPLC size exclusion, and 35,000 and 20,000 by SDS-PAGE under non-reducing and reducing conditions, respectively. Art v II was found to consist of 6(7) isoforms with pI 4.10, 4.20 (major component), 4.35, 4.45, 4.55, 4.65, (4.80). The glycoprotein allergen had a protein to carbohydrate ratio of 10:1 and the carbohydrate part contained mannose (70.7%), N-acetyl-glucosamine (17.0%), glucose (7.0%) and galactose (5.3%). In R(R)IE the purified allergen bound IgE from 5 (33%) of 15 sera from patients with clinical allergy against mugwort pollen and from 13 (52%) of 25 sera from patients selected only on the basis of a RAST-class 4 against mugwort pollen. PMID- 2233756 TI - Confirmation by peptide sequence and co-expression on various cell types of the identity of CD44 and P85 glycoprotein. AB - The p85 glycoprotein expressed on a variety of human cell types including astrocytes and lymphocytes has not been associated with the CD44 cluster. The recent demonstration that Hermes, a glycoprotein implicated in the adhesion of lymphocytes to endothelium, belongs to the CD44 cluster raises interesting questions concerning the role of this molecule on astrocytes and on non-lymphoid cells. To obtain confirmation of the identity of p85 glycoprotein and CD44, p85 glycoprotein was purified from B-chronic lymphocytic leukemia cells by affinity to monolonal 50B4-IgG and electrophoretic elution, digested with trypsin or CNBr and fractionated by reversed-phase HPLC. The sequences of three peptides were obtained which could be aligned with the amino acid sequence deduced from the CD44 cDNA at residues 49-54, 59-66 and 309-323. These constitute the first reported peptide sequences for antigens of the CD44 cluster and confirm that p85 glycoprotein is indeed the product of the CD44 gene. Since two different cDNA clones encoding molecules with cytoplasmic tails of 72 and 5 amino acids have been isolated, the isolation of peptide 309-323 confirms the existence of a processed protein with the longer cytoplasmic domain. Using a cDNA probe, we have characterized the expression of CD44 in several normal and malignant cell types. The level of CD44 mRNA was correlated with the surface expression of CD44 antigens (50B4) in several leukemic cell lines, in astrocytoma lines and in normal granulocytes. Negative cells included the Y79 retinoblastoma line, the NALM-6 leukemic line and endothelial cells. Identical mRNA species of 5.0, 2.3 and 1.7 kb were present in all CD44-positive samples, including normal granulocytes, astrocytoma, melanoma and leukemia cell lines and leukemic cells from patients. The highest level of expression of CD44 was observed on astrocytoma lines and on acute lymphoblastic leukemia cells of immature phenotype. The presence of high levels of CD44 on malignant cells could increase the ability of these cells to adhere to matrix proteins and/or to interact with endothelium, thus potentially altering their capacity for invasiveness and metastasis. PMID- 2233757 TI - Complement killing of human neuroblastoma cells: a cytotoxic monoclonal antibody and its F(ab')2-cobra venom factor conjugate are equally cytotoxic. AB - Only a few monoclonal antibodies mediate complement lysis of tumor cells, but for several antibodies it has been demonstrated that a complement-activating function can be introduced by covalent coupling of cobra venom factor (CVF), a non-toxic glycoprotein which is a structural and functional homologue of human complement component C3. In this study we compared the efficacy of complement killing of human neuroblastoma cells by the complement-activating monoclonal antibody 3F8 directed against the GD2 ganglioside antigen with that of its F(ab')2-CVF conjugate. At equal numbers bound per cell the 3F8 antibody and the 3F8 F(ab')2 CVF conjugate were found to be equally cytotoxic in the presence of complement from several species including human. Maximal killing reached up to 98%. The kinetics of killing and the bivalent metal requirement confirmed that the cytotoxic activity of the 3F8 antibody is mediated via the classical pathway and that of the 3F8 F(ab')2-CVF conjugate via the alternative pathway. To achieve a comparable degree of killing, an approximately eight-fold higher concentration of the 3F8 F(ab')2-CVF conjugate was required which appears to be a consequence of the approximately eight-fold lower binding activity of the 3F8 F(ab')2-CVF conjugate compared to the intact 3F8 antibody. Our data suggest that the coupling of CVF to non-cytotoxic antibodies allows the generation of conjugates with a cytotoxic activity similar to that of inherently cytotoxic antibodies. PMID- 2233758 TI - Polyvalent interaction of antibodies with bacterial cells. AB - We have studied the physical-chemical characteristics of the interaction of peroxidase-labelled rabbit antibodies with Bacillus sp. bacterial cells. The antibodies are able to bind bivalently with two antigen sites on the bacterial cells with the formation of intramolecular "cyclic" complexes. A kinetic model is proposed suggesting the existence of monovalent and bivalent cell surface antigens. The equilibrium constant of the bivalent IgG binding to the bacterial cell is by two orders of magnitude higher as compared to monovalent Fab fragments. The intramolecular reaction between the free active site of the monovalently bound antibody and a free antigen site on the cell surface is the rate limiting step of the polyvalent interaction. Formation of the cyclic complexes seems to be accompanied by essential tension of bonds and deformation of the IgG molecule. Agglutination of bacterial cells was also studied. The cell agglomerate size dependence on the antibody concn has a threshold. Agglutination proceeds under conditions where the antigen-antibody binding on the cell surface is far from equilibrium. PMID- 2233759 TI - Recognition of imidazole and histamine derivatives by monoclonal antibodies. AB - The different ways of raising antibodies to histamine are reviewed. High affinity monoclonal antibodies could be raised only against derivatized histamine. Succinyl glycinamide derivatization provided the basis of an efficient radioimmunoassay. In this paper the molecular pattern and the thermodynamical properties of histamine recognition were thoroughly investigated. Only the neutral form and not the cationic form of imidazole was recognized. As expected, the ligand recognition increased, with improved structural homology to the immunogen. However, a detailed analysis revealed a zwitterionic effect whenever a carboxylic group was present on the side chain of the ligand. PMID- 2233760 TI - [Treatment of acute bronchial obstruction in childhood]. PMID- 2233762 TI - [Acute bronchial obstruction in infancy--therapeutic concepts]. AB - Acute wheezing in infancy is a very common problem in pediatric practice. One diagnosis is RSV-bronchiolitis in the very young infant, but more often acute wheezy bronchitis will be diagnosed, which is also induced by viral infection and may be the first exacerbation of asthma. Both require the same basic therapy, but there ist no agreement about the therapy with bronchodilators. Similarly their is controversy about the use of antiviral agents for RSV-bronchiolitis. The most important strategies for the acute, and not the long term therapy, will be reviewed and discussed. PMID- 2233761 TI - [Bronchial asthma: allergy and inflammation. Principles of rational asthma therapy]. AB - Improved concepts concerning the pathogenesis of chronic bronchial asthma, the role of air pollutants, infections, and allergic reactions are the basis of established therapeutic principles and the development of new drugs: Allergens initiate long lasting inflammatory processes ("late phase reactions") in the bronchial system. This inflammation causes bronchial hyperreactivity and altered lung function. A large number of inflammatory cells and mediators are involved. Air pollutants and infections can act in the same way. Asthma treatment should focus in the inflammatory process, start early and prevent and treat both chronic inflammation and acute bronchospasm. PMID- 2233763 TI - [Miller-Dieker syndrome (type I lissencephaly) with specific EEG changes]. AB - We present the case report of a girl with a subtype of Lissencephaly syndrome, type I, "Miller-Dieker syndrome", pointing out the specific EEG features in infancy and early childhood. The following pathognomonic EEG manifestations may confirm the diagnosis of an lissencephalic syndrome: abnormally fast background activity of an extraordinary high voltage increasing with age, missing topographic structuring, no reactivity to sleep or medication, unusually high voltaged sharp-slow-wave complexes. PMID- 2233764 TI - [Subsepsis allergica in a patient with type I polyglandular autoimmune syndrome]. AB - A 10.6 year old Turkish girl developed + the signs of a polyglandular autoimmune syndrome (PGA) type I since her first year of age. Apart from the endocrine and non-endocrine symptoms of PGA, she suffered from an acute state of illness with therapy-resistant fever and multiform exanthemas in the early course of disease. All included the criteria of Wissler-Fanconi syndrome became clear which has not yet been reported in association with PGA. Although this syndrome generally is considered an equivalent of Still's syndrome, rheumatoid symptoms could not be ascertained during the following 9-year-course of PGA. PMID- 2233765 TI - [Cystic fibrosis and celiac disease. Report of two cases]. AB - Two patients with cystic fibrosis who subsequently developed celiac disease are described. Difficulties in the diagnosis of coexistence of both diseases are discussed. PMID- 2233766 TI - [Congenital intracranial teratoma with exophthalmos]. AB - We report the rare case of a term newborn with an excessively large congenital, intracranial teratoma expanding into the right orbita and maxilla. The main symptoms were a total unilateral exophthalmos, a tumorous mass in the right cheek, macrocephaly with wide sutures, and a bulging fontanel. The diagnosis was confirmed by sonography, computed tomography and an exploratory excision from the retromaxillary region. PMID- 2233767 TI - [Bilateral adrenal pheochromocytoma. Diagnosis and follow-up using the clonidine test and measurement of plasma neuropeptide Y concentration]. AB - The role of the clonidine suppression test and determination of the plasma concentration of noradrenaline and of neuropeptide Y (NPY) for the diagnosis and monitoring of bilateral pheochromocytoma was studied in a ten year old girl. Prior to tumor removal plasma concentration of noradrenaline (25.9 nmol/l) and NPY (14 pmol/l) were markedly elevated. Inhibition of central sympathetic activity by clonidine (150 micrograms orally) did not lower the plasma concentration of noradrenaline (70.4 nmol/l) and NPY (52.6 pmol/l). However in an adolescent boy with renal hypertension plasma concentration of noradrenaline and NPY fell following clonidine application (noradrenaline from 1.9 to 1.3 nmol/l, NPY from 3.6 to 2.4 pmol/l). After complete removal of the pheochromocytoma noradrenaline and NPY fell back to normal. PMID- 2233768 TI - [Models for management of premature and sick newborn infants--a structural analysis]. PMID- 2233769 TI - [The effect of D-penicillamine on experimental liver cirrhosis induced by CCl4]. AB - Authors examined the effect of D-penicillamin (Pw) on liver cirrhosis induced by chronic CCl4 and phenobarbital (Pb) treatment in Fischer 344 rats. Morphometric analysis of quantity of connective tissue fibres did not show decrease on the effect of Pe treatment. Quantity of hydroxiproline, which is one of the parameters of coll ahen decrease, did not change significantly on effect of drug, but only compared to CCl4 and Pb treated control. Quantity of glycosaminoglycan showed increase following Pe treatment. Lymphocyte stimulation by Con-A was different in CCl4 and Pb and Pe treated groups, respectively. According to our examinations in case of liver fibrosis cirrhosis induced by CCL4-PB treatment in rats the Pe treatment proved to be unsuccessful. It seems that Pe is effective only in forms of cirrhosis accompanied by significant copper accumulation, by decrease of toxic effects of copper. PMID- 2233770 TI - [Changes in the femoral vein in dogs as an effect of experimental lymphedema]. AB - Authors studied changes of femoral vein developed by the effect of examinations experimental lymphoedema in dogs. Light and electronmicroscopic were performed from femoral vein of animals killed on 3rd and 14th postoperative day, and biomechanical examinations were done too from dogs killed on 14th postoperative day. In vessel wall edema, fibrosis, and in valves infiltration consisting of macrophages, neutrophilic granulocytes and of mesenchymal cells were observed. Biomechanical examinations did not show significant deviation. Their results suggest the possibility that extremital lymphoedema also in man may contribute to development of varicosity or to its aggravation. Experimental lymphoedema of lower limb of dog can be proposed as model experiment to the complex study of pathogenesis of development of varix. PMID- 2233771 TI - [Morphological of biological effects of progestagens]. AB - During their clinical studies on human endometric tissue in normal and pathologic condition authors attempt to determine morphologic changes occurring to the effect of progestagens. Klt is established that progestagens cause typical morphologic changes which are manifested in regression of endometrium on varying scale. The most striking effect is exerted on mitochondria among respective cell organelles; it means the damage of these structures. Decrease of enzymatic processes linked to mitochondrea, caused by effect of progestagens, presumably inhibits cell proliferation. Inhibition of cellular oxidation in pathologic conditions, like in endometric hyperplasia and in highly differentiated cases of endometric cancer, can be of therapeutic effect. Their studies provide opportunity to interpretation of morphologic changes performed in hormone dependent tissues and to better understanding of its role in carcinogenesis of sexual hormones. PMID- 2233773 TI - [Methods of informatics in pathology]. AB - Author surveys literature of pathology and medical informatics of last 25 years regarding pathological information systems. He studies changes of used hardware and software means related to development of computer technique. Some issues of use of pathological informatics in Hungary are also touched on basis of literature. PMID- 2233772 TI - [Immunohistology of Hodgkin's disease. Use of monoclonal antibodies in the analysis of the pathomorphology of Hodgkin's disease]. AB - Author studied cryostatic sections of lymph node biopsy of 45 untreated patients suffering in lymphogranulomatosis by known T and B lymphocyte, macrophage histiocyte, Ia and HLA-DR and transferrine receptor specific monoclonal antibodies (moats). In HK-LP, HK-NS, HK-MC and HK-LD the infiltrations were formed by phenotyped lymphocytes contrary to HK-NP, where HK nodules were composed of B-cells. In HK-LPs T lymphocytes were of T-helper phenotypes, and these T-cells were observed in cases of HH-NS and HK-MC, abounding in lymphocytes, besides a few T-suppressor cells. The number of lymphocyte of latter type increased in HK-NS and and HK-MC, poor in lymphocytes and in HK-LD. The giant cells had positive reaction with Leu3a, Leu5, OKIa, HLA-DR and transferrine receptor specific moats. SR cells are such anaplasic cells or probably tumorous cells developed by cell hybridization, which are able to antigen expression characteristic of various hemopoietic cell line and of activated cells, respectively. PMID- 2233774 TI - [Adenomatoid tumor of the uterus: report of 3 cases]. AB - Adenomatoide tumor of uterine is reported on the basis of study of three surgical preparations. Tumors were detected as causal finding in uterines removed for other changes. The tumor can be a histopathologic diagnostic problem. It is likely considered to be of mesothelial origin. Its two forms are separated; in one also smooth muscle cells take part in growth. PMID- 2233775 TI - [Morphologic and morphometric analysis of atheromatous changes in the aorta in silibinin-treated cholesterin-fed rabbits]. AB - Authors studied the effect of Silibinin of antioxidative effect on cholesterin sclerosis of rabbits. Qualitative analysis of aorta sections, macroscopic and microscopic morphometric examination of aorta were the applied methods. Their results seem to show that Silibinin has a favourable influence on cholesterin sclerosis. According to their opinion only joint use of qualitative and quantitative macroscopic and microscopic methods can provide basis for really accurate judgment of any atheromatose change. PMID- 2233776 TI - [Pathomechanism of the development of chronic obliterative transplantation arteriopathy in human kidney allografts]. AB - Authors examined cells participating in intimaproliferation in transplantation arteriopathy ultrastructurally in needle and wedge biopsy material from 40 transplanted kidneys, and immunohistochemically in 10 cases. In early biopsies- even in two control kidneys--it could be observed that the smooth muscle cells of media are in direct contact with endothel cells by their small processes. Processes can fulfil a receptor function and can transmit endothel noxa to smooth muscle cells. Smooth muscle cells of media react to endothel damage caused by rejection with migration to intima and during this period they are transformed to myofibroblasts (myointimal cells). In the mean time inflammatory cells (mainly macrophages, helper and cytotoxic cells in lower number) from the lumen infiltrate the intima, and mediators, enzymes released from them can inspire smooth muscle cells to further proliferation, migration to intima and transformation to myofibroblast. To effect of mediators (gamma interferon) released from inflammatory cells, the myointimal cells during rejection will press out 2nd class transplantation antigens (HLA-DR), and as vicious circle it further aggravates immune reply to graft, causing vascular damage, intimaproliferation. PMID- 2233777 TI - [Clinico-pathological observations in myocardial rupture]. AB - In their material of 10 years authors describe 42 myocardial ruptures developed as complication of acute myocardial infarct. The rupture developed in the acute stage of infarct. Rupture of anterior wall infarct is the most frequent. The most decisive clinical factor in development of rupture is the loading in acute stage, from pathologic aspect the strongly infiltrated, transmural infarct is considered the most decisive pathologic factor. Diabetes mellitus and hypertonia can predispose to myocardial rupture. PMID- 2233778 TI - [Histological changes in the appendix in the prodromal stage of measles]. AB - Morphological changes of adenoid tissue associated with morbilli are known. However, it is less known that the disease may start with symptoms of acute appendicitis and on the basis of histological picture morbilli can be raised or rendered probable, respectively, before appearance of typical clinical symptoms. Among morbilli cases of recently increased number the later developed morbilli was diagnosed from appendix in an appendectomy performed on a patient being in prodormal stage. PMID- 2233779 TI - [Localization of the structural gene for botulinum neurotoxin type A using synthetic DNA probe for neurotoxin light chain]. AB - To obtain the information on the genetic control of toxin production in the botulism causative agents, the oligonucleotides were synthesized as the molecular probes by translation of the amino acid sequence of the botulinic type A neurotoxin. The optimal conditions for hybridization of botulinic DNA with the synthetic DNA probes were determined and the probes specificity was demonstrated. The DNA fragments homologous to the probes used were shown to belong to bacterial genome, but not to bacteriophage one. PMID- 2233780 TI - [Isolation of transmissible cointegrates of Yersinia pestis plasmids pYV and pYT with the plasmid RP4::Mu cts 62, IncP1]. AB - The transmissible cointegrates of the Yersinia pestis plasmids pYV and pYT with the broad host range plasmid RP4::Mu cts62 of the incompatibility group IncP have been constructed by the in vivo recombination. The cointegrative plasmid pKR14 (pYV76 omega RP4::Mu cts62) conferred on the transconjugants the properties of Ca2(+)-dependence at 37 degrees C, V-antigen synthesis, RP4 plasmid markers (ApR, KmR, TcR), immunity to the lysis by the bacteriophage Mu cts62 and incompatibility with the homologous replicon pYV76. Cointegrates pKR103 and pKR106 (pYT omega RP4::Mu cts62) conferred on the transconjugant clones the ability to synthesize the "mouse" toxin and fraction I. The capability of Escherichia coli cells to synthesize the latter products has been demonstrated together with the deficiency of these cells to transport the synthesized fraction I to the cell surface. PMID- 2233781 TI - [Expression of Yersinia pestis antigens encoded by the Ca2+-dependence plasmid]. AB - Antigens coded by the Ca2(+)-dependance plasmid were found in the cultural medium, cytoplasm and outer membranes of the three monoplasmid (pCadV) strains of Yersinia pestis with the different basic properties. The presence of 20 mM of Mg2+ at least in the medium is necessary for optimal expression of these proteins. The existence of strain differences in the bacterial cells reaction to temperature, cultivation medium has been demonstrated. No difference in the pCad dependent proteins was found in Yersinia pestis and the causative agents of pseudotuberculosis, enterocolitis. PMID- 2233782 TI - [Covalent-bound aggregates of equine venezuelan encephalomyelitis virus induced by UV-irradiation]. AB - Formation of Venecuelan equine encephalomyelitis virus (VEE) aggregates induced by UV-light has been studied. The high doses of UV-irradiation induced the protein-protein cross-links resulting in formation of fast sedimenting viral structures. The latter structures are supposed to be presented by the aggregates of several virions linked by the UV-light induced RNA-protein and protein-protein covalent bonds. The lesions in the fine structure of virion envelope was registered by the electron microscopy technique. PMID- 2233783 TI - [Polypeptides of African swine fever virus]. AB - The published data on the characteristics and properties of structural and nonstructural polypeptides of the African porcine virus are reviewed. Localization of the viral proteins in virions and infected cells, kinetics of biosynthesis, glycosylation, phosphorylation and the antigenicity of the proteins are discussed. PMID- 2233784 TI - [New shuttle-type vectors for cloning in Escherichia coli and Agrobacterium tumefaciens]. AB - The vectors capable of replication in Escherichia coli and Agrobacterium tumefaciens have been constructed on the basis of the plasmid pUB5502. The constructed vectors pVA12, pVA12-2, pVA12-4 contain the mini-replicon and trimethoprim resistance gene (Tp) of a broad host-range plasmid R388 (IncW). The pVA12 vector (8.8 kb) has been constructed by insertion of a kanamycin resistance gene (Km) from the plasmid pUC-4K into a Psti site. It possesses 7 unique restriction sites for XhoI, SmaI, PvuI, PvuII, HindIII, EcoRI, BamHI and the markers for kanamycin and trimethoprim resistance (Km and Tp). The pVA12-2 and pVA12-4 vectors were obtained as a result of changing of the PvuII-EcoI fragment of pVA12 carrying the Tp gene for the PvuII-EcoRI fragment of pBR322 carrying the Tc gene. These plasmids have the same size of 9.7 kb and 8 unique sites for restriction endonucleases XhoI, SmaI, PvuI, PvuII, EcoRI, EcoRV, SalI, BalI and Km and Tc genes. No difference has been registered between the two plasmids by restriction analysis, but pVA12-4 has the dramatically increased copy number in Escherichia coli cells. All three vectors are transferable to Agrobacterium tumefaciens with the same frequencies by transformation or conjugation and do not affect the oncogenicity of pTi. PMID- 2233785 TI - [Relation between the Yersinia phage and bacteriophages isolated from the environment]. AB - The bacteriophage designated RD2 has been isolated from the sewage in Rostov-on Don city and studied. The morphology of bacteriophage particles and the biological properties of the bacteriophage make it related to the plague bacteriophage isolated by D'Errel. The molecular masses of the compared bacteriophages are almost identical being 26.4 +/- 0.4 Md for RD2 and 24.7 +/- 0.2 Md for D'Errel bacteriophage. The DNAs of the bacteriophages share 80% of homology and possess 15 nonhomologous regions scattered along the genomes. The phages are serologically related. The DNAs of both bacteriophages give the similar pattern of hydrolysis by restriction endonuclease EcoRV, but have the different sensitivity to many other restriction endonucleases. The protein specter of bacteriophage RD2 contains 18 polypeptides (11 minor ones), while the one of D'Errel bacteriophage contains 7 polypeptides similar in molecular mass with the polypeptides of RD2. The bacteriophage RD2 cannot be considered one of the plague causative agents of bacteriophages since the region where it has been isolated has a long epidemiological and epizootical record of absence of plague. PMID- 2233786 TI - [The effect of recombinant plasmids containing the antisense sequence of E. coli gene rplJ on the expression of tester gene rplJ-lacZ]. PMID- 2233787 TI - [Inactivation of bacteriophage PM2 during storage]. AB - The kinetics of bacteriophage inactivation in the medium that is optimal for its storage has been studied at temperatures from 4 to 55 degrees C. The plot of Arrhenius dependence of the constant of inactivation rate consists of the two linear parts with the energies of activation Ea = 25 kcal/mol for 4-37 degrees C and Ea = 91 kcal/mol for 37-55 degrees C. The DNA of inactivated bacteriophage remained mostly in superspiralized form and completely preserved its biological activity as tested by transfection in spheroplasts. The analysis of inactivation kinetics suggests ageing of virions cultivated at 4 degrees C. The addition of watersoluble antioxidant amoxipin did not change the inactivation kinetics. The addition of antioxidant ionol with twin-80 increased the inactivation that was paralleled by the bacteriophage DNA degradation. PMID- 2233788 TI - [Antisense RNA in transgenic plants]. AB - The data on the effects of antisense RNA in plants is reviewed. Results of expression of the genes for selective markers, antisense reporter genes, functioning and viral genes are analyzed. The molecular mechanisms for inhibiting effects of antisense RNA and the potential use of the phenomenon in the plants biotechnology are discussed. The formation of long duplexes between the antisense RNA and messenger RNA are supposed to be irrelevant to suppression of gene expression in plants by the antisense RNA. PMID- 2233789 TI - [Interaction of staphylococcal alpha-toxin with biomembranes]. AB - The recent data on staphylococcal alpha-toxin, its functions, methods for its purification, forms are presented in the review. The problem of a target for toxin molecule is discussed. PMID- 2233790 TI - [Directed cloning of the HLA-B27 gene isolated from a patient with ankylosing spondylitis (Bechterew's disease)]. AB - The authors have used the modified method of the direct gene cloning suggested by Nichols et al to isolate HLA-B27 gene from a patient suffering from ankylosing spondylitis. Five restriction enzymes (ClaI, HindIII, SnaBI, PvuI, SalGI) which had no recognition sites within the 6.0 kb EcoRI-BamHI-DNA fragment supposedly containing the HLA-B27 gene have been chosen by blotting-hybridization of the restriction fragments of the patients DNA with HLA-B27-specific probe. The 6.0 +/ 0.5 kb DNA fragments were isolated and cloned after the DNA treatment by 300 micrograms of all of these restriction enzymes. The obtained mini-library containing 280 recombinants has been screened with the use of HLA-B27 specific oligonucleotide probe. The clone PB27-2 has been isolated the restriction map of which is identical to HLA-B27k. The authors are planning to determine the sequence of the isolated gene in order to find a possible structural defect in it. PMID- 2233791 TI - Alkylation, mutagenesis and repair. PMID- 2233792 TI - Role of DNA methylation in the activation of proto-oncogenes and the induction of pulmonary neoplasia by nitrosamines. AB - The relationships between DNA methylation and repair induced by the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to the activation of proto-oncogenes and the induction of pulmonary neoplasia by this carcinogen is described. The formation of the O6-methylguanine (O6MG) adduct following metabolic activation of NNK appears to be a major factor in the induction of lung tumors in both rats and mice and in the activation of the K-ras oncogene in lung tumors from A/J mouse. The potent carcinogenicity of NNK in the rat lung correlated strongly with cell specificity for formation and persistence of the O6MG adduct in the Clara cells. This conclusion was supported by studies with nitrosodimethylamine (NDMA), a weak carcinogen in the rodent lung. Treatment with NDMA was not associated with any pulmonary cell specificity for DNA methylation. The high affinity for activation of NNK compared to NDMA was ascribed to a difference in cytochrome P-450 isozymes involved in the activation of these two nitrosamines. In the A/J mouse, the induction of pulmonary tumorigenesis involved direct genotoxic activation of the K-ras proto-oncogene as a result of the base mispairing produced by formation of the O6MG adduct. In contrast, the induction of pulmonary tumors in the rat by NNK does not appear to involve the ras pathway. It is apparent that different molecular mechanisms are involved in the development of pulmonary tumors by NNK in the mouse and rat. The studies described in this paper illustrate the utility of performing dose response experiments and the quantitation of DNA methylation and repair in not only target tissues but also target cell types. The fundamental knowledge gained from unraveling the mechanism of carcinogenesis by NNK could lead ultimately to the identification of factors important in the development of human lung cancer. PMID- 2233793 TI - DNA alkylation by the haloethylnitrosoureas: nature of modifications produced and their enzymatic repair or removal. PMID- 2233794 TI - Sequence-dependent formation of alkyl DNA adducts: a review of methods, results, and biological correlates. AB - Understanding the influence of the DNA sequence on chemical-DNA interactions may provide insight into the processes of chemical carcinogenesis and mutagenesis. This article provides a brief overview of studies and methods devoted to examining the distribution of DNA adducts produced by alkylating agents. Particular emphasis is placed on discussion of DNA adducts generated by simple alkylating agents and the role that their distribution may play in the generation of mutational hotspots. PMID- 2233795 TI - The control of O6-methylguanine-DNA methyltransferase (MGMT) activity in mammalian cells: a pre-molecular view. AB - Human peripheral blood lymphocytes (PBLs) can have a range of O6-methylguanine DNA methyltransferase (MGMT) activities. PBLs from some individuals may have almost no MGMT activity. Such individuals have most often been subject to malignancy or to immunodeficiency disease. Long-term lymphoblastoid lines (LCLs) prepared from PBLs of normal subjects by Epstein-Barr virus (EBV) transformation have MGMT activities which are in general somewhat higher than the PBLs from which they derive. Such cultures are therefore generally MGMT-positive. Only in rare cases, and generally from patients with low MGMT activity, are freshly obtained lines with very low activity obtained. There is however a 4-fold range of MGMT activity over which multiple lines derived from the same PBL sample can be found. Long-term cultivation can lead to LCLs with low activity as well as to lines of high activity. On rare occasions an MGMT-positive line may, within a few divisions, give a negative line. Some (but not all) MGMT-negative (or very low) lines have been known to gain (some) activity. Chinese hamster ovary (CHO) cell lines are in general very low in MGMT activity. Lines of higher activity can be selected by treatment with mutagenic crosslinking alkylating agents. Chinese hamster lines with high MGMT activity can be obtained by transfection with human DNA from MGMT-positive cells. Lines with significant activity can also be obtained by transfection of CHO cells with human DNA from MGMT-negative (or very low) cells. Resistance to MNNG treatment can be acquired without the acquisition of significant MGMT activity. Crosses of lines of high and low MGMT activity give equivocal results. Hybrids of low x low activity have no activity. Crosses of positive x positive strains give varied results. It has not been possible to identify MGMT-positive hybrids as including one particular chromosome by this type of experiment. There is no evidence for a general adaptive effect on MGMT synthesis greater than the variation within the cell cycle. PMID- 2233796 TI - The E. coli ogt gene. PMID- 2233797 TI - Macromolecular adducts of ethylene oxide: a literature review and a time-course study on the formation of 7-(2-hydroxyethyl)guanine following exposures of rats by inhalation. AB - The results of efforts to identify and quantify macromolecular adducts of ethylene oxide (ETO), to determine the source and significance of background levels of these adducts, and to generate molecular dosimetry data on these adducts are reviewed. A time-course study was conducted to investigate the formation and persistence of 7-(2-hydroxyethyl)guanine (7-HEG; Fig. 1) in various tissues of rats exposed to ETO by inhalation, providing information necessary for designing investigations on the molecular dosimetry of adducts of ETO. Male F344 rats were exposed 6 h/day for up to 4 weeks (5 days/wk) to 300 ppm ETO by inhalation. Another set of rats was exposed for 4 weeks to 300 ppm ETO, and then killed 1-10 days after cessation of exposures. DNA samples from control and treated rats were analyzed for 7-HEG using neutral thermal hydrolysis, HPLC separation, and fluorescence detection. The adduct was detectable in all tissues of treated rats following 1 day of ETO exposure and increased approximately linearly for 3-5 days before the rate of increase began to level off. Concentrations of 7-HEG were greatest in brain, but the extent of formation was similar in all tissues studied. The adduct disappeared slowly from DNA, with an apparent half-life of approx. 7 days. The shape of the formation curve and the in vivo half-life indicate that 7-HEG will approach steady-state concentrations in rat DNA by 28 days of ETO exposure. The similarity in 7-HEG formation in target and nontarget tissues indicates that the tissue specificity for tumor induction is due to factors in addition to DNA-adduct formation. PMID- 2233798 TI - Properties of mammalian O6-alkylguanine-DNA transferases. PMID- 2233799 TI - Mutagenesis by N-nitroso compounds: relationships to DNA adducts, DNA repair, and mutational efficiencies. AB - The relationships between DNA alkylation, DNA repair and mutagenesis by N-nitroso compounds in Salmonella were examined. DNA adducts formed by treatment of the bacteria with N-nitroso compounds were monitored. Critical to the study was establishing which adducts led to mutations. Two methods were employed. In one, correlations in the dose-responses for adducts and mutagenesis were sought. For instance O6-methyl- and -ethyl-guanine, in contrast to other adducts, exhibited thresholds in their accumulation in Salmonella DNA, and mutagenesis at GC base pairs also exhibited the same threshold, suggesting a dependence of mutagenesis on the O6-alkylguanines. In the second method, mutagenesis induced by different mutagens with overlapping adduct spectra was compared. For example, EMS and ENU generate similar ratios of adenine adducts, but only ENU produces thymine adducts, and only ENU induced AT-GC and AT-CG base changes. These observations suggested that ethylthymines led to these mutations. Furthermore, it was found that these mutations were largely dependent on the presence of the plasmid, pKM101, indicating that error-prone repair activity contributes importantly in their processing to mutations. When DNA adducts by N-nitrosopyrrolidine were examined it was found that only one major adduct was detected in an excision repair-deficient strain, and that this adduct was not present in a repair proficient strain. Mutagenesis was also greatly reduced in the proficient strain, suggesting that mutagenesis was dependent on this adduct. From the relationships between premutagenic adduct levels and mutagenesis it was possible to calculate estimated values for the mutational efficiencies for several adducts. This calculation assumed an average distribution of adducts and mutations and required knowledge of the target size and the types of mutations that could lead to phenotypic changes. For the unrepaired O6-methyl- and -ethyl-guanines, and the O ethylthymines the mutational efficiencies were high (ca. 30-70%), but for the N nitrosopyrrolidine adduct it was low (ca. 1%). Initial studies were carried out on the mutational specificities of two higher homologue N-nitroso compounds (the N-nitroso-N-propyl- and N-butyl-nitroguanidines) in uvrB/pKM101 strains. This class of nitroso compounds is known to form similar DNA adducts as ENU. Their specificities were similar to that of N-nitroso-N-ethylurea at a high dose except the fraction of mutations at AT base pairs was reduced. The fraction of GC-CG transversions was although low, increased. The mutational specificities of N nitroso-N-methylurea and N-nitrosopyrrolidine were significantly different from the specificity of E PMID- 2233800 TI - Site-specifically alkylated oligodeoxynucleotides: probes for mutagenesis, DNA repair and the structural effects of DNA damage. PMID- 2233801 TI - Molecular dosimetry for sister-chromatid exchange induction and cytotoxicity by monofunctional and bifunctional alkylating agents. AB - The induction of sister-chromatid exchanges (SCEs) and cytotoxicity in 9L cells treated with monofunctional and bifunctional alkylating agents has been investigated. Three classes of monofunctional and bifunctional agents were studied: nitrosoureas, mustards and epoxides. Independent of class the bifunctional agents were 55-630-fold more effective at inducing SCEs and 300-2400 fold more effective at inducing cellular cytotoxicity than the corresponding monofunctional agents. Comparing the induction of SCEs and cytotoxicity by these agents showed that these two cellular responses to DNA damage are highly correlated. The extent of DNA alkylation in cells treated with 1-ethyl-1 nitrosourea (ENU) or 1-(2-chloro-ethyl)-1-nitrosourea (CNU) was similar indicating that the increased effectiveness of CNU to induce SCEs and cytotoxicity was not due to increased DNA alkylation. Molecular dosimetry calculations indicate that for CNU and ENU treatment of 9L cells there are 116 and 8500 alkylations per SCE induced and 2.6 x 10(4) and 4.6 x 10(6) alkylations at the dose required to reduce survival of 9L cells by 90%. Comparison of the DNA alkylation products produced by CNU and ENU treatment of 9L cells suggests that the formation of the intrastrand crosslink N7-bis(guanyl)ethane and the interstrand crosslink 1-(3-deoxycytidyl)-2-(1-deoxyguanosinyl)ethane by CNU is responsible for the increased effectiveness of CNU treatment at both induction of SCEs and cytotoxicity. PMID- 2233803 TI - Antibodies to DNA alkylation adducts as analytical tools in chemical carcinogenesis. PMID- 2233802 TI - Induction of proteins involved in the repair of alkylated bases in mammalian cells by DNA-damaging agents. PMID- 2233804 TI - Regulation of O6-methylguanine-DNA methyltransferase expression in the Burkitt's lymphoma cell line Raji. AB - We have investigated the expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase in the Burkitt's lymphoma cell line Raji. An existing mutant Raji cell line which lacks thymidine kinase activity had previously been shown to be Mex- and to no longer express O6-methylguanine-DNA methyltransferase. We report here that in addition to the methyltransferase and thymidine kinase, a third enzyme with an unrelated function, galactokinase, is also not expressed in Raji cells. The control of thymidine kinase expression is post-transcriptional and it is possible that galactokinase and methyltransferase can share a common post-transcriptional regulation with thymidine kinase. PMID- 2233805 TI - Alkylation damage, DNA repair and mutagenesis in human cells. AB - 17 human cell lines that differ significantly in level of O6-alkylguanine-DNA alkyltransferase (AGT) activity were identified by comparing their sensitivity to the cytotoxic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and determining the level of AGT activity in cell extracts from the various lines by measuring the decrease in radiolabeled O6-methylguanine from DNA, using high performance liquid chromatography. 9 lines exhibited high levels of AGT activity, 2 showed an intermediate level (25-50% of the mean of those with the higher levels), and 6 exhibited very low or virtually undetectable levels of AGT. Included were several lines that are very deficient in capacity for nucleotide excision repair. When representatives from the 3 categories of cell lines defined by the level of AGT activity were compared for sensitivity to the cytotoxic and mutagenic effect of MNNG, they showed an inverse correlation between the degree of cell killing and frequency of mutants induced and the level of AGT activity. The cells' capacity for nucleotide excision repair did not affect these results. Exposure of cells with a high level of AGT activity to O6-methylguanine in the medium reduced the AGT activity 60-80%. These pre-treated cells exhibited a significantly higher frequency of MNNG-induced mutants than did cells that were not pre-treated, suggesting that the O6-methylguanine lesion in DNA is responsible for a significant proportion of the mutations induced. Cell strains containing substrates for assaying intrachromosomal homologous recombination were constructed using parental cell lines from each of the 3 categories of AGT activity. These strains showed an inverse correlation between the level of AGT activity and the frequency of MNNG-induced recombination. When various cell lines representing the 3 categories of AGT activity were compared for sensitivity to ethylnitrosourea, the results were consistent with AGT and nucleotide excision repair playing a role in preventing cell killing and mutation induction by this agent. PMID- 2233806 TI - DNA alkylation damage: consequences and relevance to tumour production. PMID- 2233807 TI - Properties of mer- HeLa cells sensitive or resistant to the cytotoxic effects of MNU; effects on DNA synthesis and of post treatment with caffeine. AB - A line of HeLa cells was shown to be particularly sensitive to N-methyl-N nitrosurea (MNU) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but not to a variety of other cytotoxic agents. A resistant line (designated HeLa/A22), was derived by treating HeLa cells repeatedly with MNU. Both the sensitive (HeLa) and resistant (HeLa/A22) cells have a mer- phenotype based both on their reduced rates of loss of O6-methylguanine (O6-MeG) from DNA and their low levels of the enzyme O6-methylguanine methyltransferase (MT). HeLa cells are therefore sensitive to unrepaired O6-MeG in DNA while the HeLa/A22 cells are resistant to unexcised O6-MeG and thus the A22 cells have the mer-rem+ phenotype. MNU produced an immediate dose-dependent inhibition of DNA synthesis in cultures of both sensitive and resistant cells which increased with time until about 4 h after treatment. DNA synthesis then recovered to near control rates in both sensitive and resistant cells before then exhibiting a progressive decrease after about 24 h. DNA synthesis was more depressed at these late times after treatment in cultures of sensitive cells than in those of similarly-treated resistant cells. DNA synthesis remained depressed in sensitive cells but recovered 3 days after treatment in resistant cells. Post treatment incubation of MNU-treated HeLa cells with caffeine did not increase the toxic action of MNU. In contrast, post treatment of the resistant HeLa/A22 cells with caffeine resulted in a dramatic increase in the toxic effects of a higher equitoxic dose of MNU. The depressed rate of DNA synthesis observed in both cell lines after high doses of MNU was partially reversed by post treatment with caffeine in both sensitive and resistant cells. These observations can be interpreted in terms of the effects of caffeine on DNA replication in treated cells. PMID- 2233808 TI - Immunocytochemical analysis of in vivo DNA modification. AB - In the past decades a large number of DNA adducts induced in the intact animal by alkylating agents have been identified. The formation and repair of these adducts are important determinants, not only of mutagenesis, tumor initiation and DNA mediated toxicity but probably also of tumor progression. Most studies on in vivo DNA modification have been performed on isolated bulk DNA. More recently, methods have been developed to study the distribution of DNA adducts at the level of either the individual gene or the individual cell. This paper reviews immunocytochemical methods to study the formation and repair of DNA adducts and other DNA modifications at the level of the individual cell. DNA modifications induced by alkylating agents and a variety of other agents including ultraviolet radiation, aromatic amines, polycyclic aromatic hydrocarbons and platinum anti cancer drugs will be discussed. Up to now, immunocytochemical analysis of in vivo modified DNA has largely concentrated on experimental animals. These studies have revealed striking heterogeneities with regard to formation and/or repair of DNA adducts in tissues from rat, hamster and mouse. Immunocytochemical adduct analysis can be used to identify in a convenient, fast and detailed way cell types, cell stages and sites in which biological effects of the adducts might be expressed. More recently, immunocytochemical analysis of DNA adducts also proved to be feasible on in situ exposed human samples. A number of existing and potential applications in the field of chemical carcinogenesis, experimental chemotherapy and molecular epidemiology are discussed. PMID- 2233809 TI - The early history of the biological alkylating agents, 1918-1968. PMID- 2233811 TI - Molecular modeling studies of O2-alkylthymines and O4-alkylthymines in DNA: structures that may be pertinent to the incorporation of the corresponding dAlkTTP into DNA by DNA polymerases in vitro. PMID- 2233810 TI - Lack of sequence-specific removal of N-methylpurines from cellular DNA. AB - The removal of N-methylpurines from the DHFR gene and an unexpressed adjacent locus located downstream occurs at similar rates and to a similar extent in dimethyl sulfate treated Chinese hamster ovary B11 cells. Furthermore, no significant differences in repair rates are observed between the strands of the active gene. These data primarily reflect the removal of the most abundant lesion produced by dimethyl sulfate, 7-methylguanine, and are in contrast to the results obtained for the removal of ultraviolet-induced cyclobutane pyrimidine dimers from the same region of the genome. Pyrimidine dimers are cleared preferentially from the transcribed strand of the DHFR gene and are removed poorly from the non transcribed complementary strand and unexpressed adjacent regions. The results suggest that DNA lesions such as dimers that block transcription are removed preferentially from active genes, whereas lesions that do not interfere with nucleic acid synthesis (i.e. 7-methylguanine) are removed at similar rates from expressed and silent loci. PMID- 2233812 TI - Site-directed mutagenesis for quantitation of base-base interactions at defined sites. AB - Two alkylation products implicated in initiation of carcinogenesis are O6 alkylguanine (m6G) and O4-alkylthymine (m4T). We have used site-specific insertion of these derivatives into oligonucleotides and measured the kinetic constants of various pairings, using both prokaryotic and eukaryotic polymerases for replication. Preliminary data are also reported for another carcinogen product, N2,3-ethenodeoxyguanosine ( epsilon G). The immediate neighbor bases play an important role in determining the frequency of specific changed basepairing and subsequent elongation of the annealed primer. However, both m4T and m6G prefer to form a type of G.T pairing which would lead to the transitions: G.C----A.T or T.A----C.G. The enzymes were the Klenow fragment of E. coli DNA polymerase I (Kf), engineered 3'----5' exonuclease-free Kf (exo-free Kf), polymerase alpha-primase complex from Drosophila melanogaster or calf thymus, and human immunodeficient virus-I reverse transcriptase (HIV-I RT). All enzymes led to approximately the same frequency of transitions. It is postulated that the mutation frequency at a given site is primarily a function of the structure of the sequence around the target site. PMID- 2233813 TI - Resistance to alkylation damage in Escherichia coli: role of the Ada protein in induction of the adaptive response. PMID- 2233814 TI - Physiological properties and repair of apurinic/apyrimidinic sites and imidazole ring-opened guanines in DNA. PMID- 2233815 TI - Why do O6-alkylguanine and O4-alkylthymine miscode? The relationship between the structure of DNA containing O6-alkylguanine and O4-alkylthymine and the mutagenic properties of these bases. AB - The carcinogenic and mutagenic N-nitroso compounds produce GC to AT and TA to GC transition mutations because they alkylate O6 of guanine and O4 of thymine. It has been generally assumed that these mutations occur because O6-alkylguanine forms a stable mispair with thymine and O4-alkylthymine forms a mispair with guanine. Recent studies have shown that this view is mistaken and that the alkylG.T and alkylT.G mispairs are not more stable than their alkylG.C or alkylT.A counterparts. Two possible explanations based on recent structural studies are put forward to account for the miscoding. The first possibility is that the DNA polymerase might mistake O6-alkylguanine for adenine, and O4 alkylthymine for cytosine, because of the physical similarity of these bases. O6 Methylguanine and adenine are similarly lipophilic and X-ray crystallography of the nucleosides has shown a close similarity in bond angles and lengths between O6-methylguanine and adenine, and between O4-methylthymine and cytosine. The second possible explanation is that the important factor in the miscoding is that the alkylG.T and alkylT.G mispairs retain the Watson-Crick alignment with N1 of the purine juxtaposed to N3 of the pyrimidine while the alkylG.C and alkylT.A pairs adopt a wobble conformation. 31P NMR of DNA duplexes show that the phosphodiester links both 3' and 5' to the C have to be distorted to accommodate the O6-ethylguanine:C pair, whereas there is less distortion of the phosphodiesters 3' and 5' to the T in an ethylG.T pair. Recent kinetic measurements show that the essential aspect of base selection in DNA synthesis is the ease of formation of the phosphodiester links on both the 3' and 5' side of the incoming base. The Watson-Crick alignment of the alkylG.T and alkylT.G mispairs may facilitate formation of these phosphodiester links, and this alignment rather than the strength of the base pairs and the extent of hydrogen bonding between them may be the crucial factor in the miscoding. If either hypothesis is correct it suggests that previously too much emphasis has been placed on the stability of the normal pairs in the replication of DNA. PMID- 2233816 TI - N-methyl-N'-nitro-N-nitrosoguanidine induced DNA sequence alteration; non-random components in alkylation mutagenesis. AB - Our approach to the study of how the molecular nature of DNA modulates the behavior of mutational sites involves the characterisation of distributions of mutations. The Escherichia coli lacI genetic/M13 cloning system allows the comparison of base substitution frequencies at a large number of sites. The observed distribution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced G:C- --A:T transition (the predominant event), and A:T----G:C transition (a relatively rare event), is strikingly non-random. Some sites of G:C----A:T mutation are almost 100 times more often mutated by MNNG than the least susceptible sites. Sites of mutation, however, do not display a continuum of mutability, but rather can be strictly demarcated by their 5' flanking base. Sites with a high frequency of occurrence share a common sequence motif, namely 5'-R-G-N-3', which is the sole apparent feature that distinguishes them from sites less commonly mutated (i.e. 5'-Y-G-N-3'). A corollary of this defined site specificity is the absence of a strand bias in MNNG-induced lacI-d mutation. The availability of specific or non-specific alkylation-repair systems does not appear to alter the distribution of mutation, which suggests that the observed mutational distribution is a direct reflection of the initial damage distribution. MNNG does not belong to that class of compounds typified by ultraviolet light or 4-nitroquinoline-N-oxide which exhibit both random and non-random components of mutagenesis. PMID- 2233817 TI - The influence of age on the inducibility of rat liver cytochrome P450IA1 (CYPIA1) and P450IA2 (CYPIA2) mRNAs. AB - The levels of the messenger RNAs for the cytochromes P450IA1 (CYPIA1) and P450IA2 (CYPIA2) were determined in liver cytoplasmic RNA of rats of various ages after maximal induction with either 3-methylcholanthrene or isosafrole and in untreated rats. An increase in the CYPIA1 mRNA levels was observed only after treatment with 3-methylcholanthrene, whereas both 3-methylcholanthrene and isosafrole were able to induce the levels of CYPIA2 mRNA. The study presented here shows that the maximal induction of these 2 mRNAs did not change with age when 3 methylcholanthrene was used as the inducing agent. Isosafrole induction did not yield higher CYPIA1 mRNA levels in young rats but reduced the amount of this mRNA in old animals to levels below the detection limit of our assay. After induction with isosafrole the levels of the CYPIA2 mRNAs in the older age groups were lower than those observed in young rats. It is concluded that with age the responsiveness to cytochrome P450 inducers may change. This change is different for the various cytochrome P450 enzymes and depends on which inducer is used. PMID- 2233818 TI - DNA damage and repair with age in individual human lymphocytes. AB - Previous biochemical studies on DNA repair competence and aging have been limited to techniques, such as alkaline elution or nucleoid sedimentation, involving mass cell populations. These techniques provide no information about the distribution of DNA damage and repair among individual cells and are unlikely to detect age dependent changes affecting a minor fraction of the cell population. We have recently described a microgel electrophoretic assay (Singh et al., 1988) that measures, at the level of the individual cell, single-strand DNA breaks and alkali-sensitive sites. Here, we employ this method to analyze DNA damage and repair in lymphocytes isolated from the peripheral blood of 31 subjects (23 males and 8 females aged 25-91 years) and exposed in vitro to 200 rads of X irradiation. While basal (pre-irradiation) levels of damage were independent of the age of the donor, an age-dependent increase in DNA damage was observed immediately following irradiation. For all subjects, the mean level of DNA damage was restored to pre-irradiation control levels within 2 h of incubation at 37 degrees C. However, a distribution analysis of DNA damage among cells within each sample indicated the presence of a few highly damaged cells (4-16%) in the 2-h sample, the occurrence of which was significantly more common among aged individuals. These data indicate an age-related decline in DNA repair competence among a small subpopulation of lymphocytes. PMID- 2233820 TI - A methyl viologen-sensitive mutant of the nematode Caenorhabditis elegans. AB - A methyl viologen (paraquat)-sensitive mutant, mev-1 (LG III), in Caenorhabditis elegans was about 4 times more sensitive to methyl viologen than the wild type. This mutant was also hypersensitive to oxygen. The brood size was about 1/4 that of the wild type. The average life span was determined to be 9.3 days as compared to 14.3 days for the wild type. The activity of superoxide dismutase (SOD), a scavenging enzyme for superoxide anion, was about half the wild-type level. We suggest that oxygen radicals may be involved in the normal aging mechanism in C. elegans. PMID- 2233819 TI - The relationship between DNA repair after alkylation damage and in vitro aging in human T-lymphocytes. AB - In vitro cultures of human peripheral blood lymphocytes, both unstimulated G0 cells as well as phytohemagglutinin (PHA) stimulated cells, have been used in the investigation of DNA repair following different types of damage, including that induced by ultraviolet light, ionizing radiation, and chemical agents. We report here repair of DNA damage in cultured normal human T-lymphocytes after treatment with the alkylating agents, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or methanesulfonate (MMS), as measured by the alkaline elution technique. T lymphocytes cultured with different sources of T-cell growth factors (TCGFs) were shown to have similar repair levels, as measured by loss of single-strand breaks. However, diminished repair was observed with in vitro culture age when T-cells were cultured with PHA and TCGF for a 3-week period. Cell-cycle analysis performed on asynchronously growing cultures indicated that differential repair with in vitro aging was not cell-cycle-related. Fluorescence Activated Cell Sorting (FACS) was used to determine the percentages of CD4+ and CD8+ T-cell subsets present during the in vitro culture periods. Cultures consisted primarily of CD4+ cells until day 20 when the percentage of CD8+ cells increased to approximately 50% of the T-cell population. Neither the absolute percentages of CD4+ and CD8+ cells not the CD4+/CD8+ ratios correlated with repair rates of cultured T-cells. Therefore, the observed decreases in the repair of alkylating agent-induced damage are not due solely to the change in the CD4+/CD8+ ratio. PMID- 2233821 TI - Hyperoxia-induced clonogenic killing of HeLa cells associated with respiratory failure and selective inactivation of Krebs cycle enzymes. AB - Cellular intoxication by elevated concentrations of O2 may be considered as a model for accelerated cellular aging processes resulting from excessive free radical production by normal metabolic pathways. We describe here that exposure of HeLa cell cultures to 80% O2 for 2 days causes progressive growth inhibition and loss of reproductive capacity. This intoxication was correlated with inhibition of cellular O2 consumption and inactivation of 3 mitochondrial flavoproteins, i.e., partial inactivation of NADH and succinate dehydrogenases and total inactivation of alpha-ketoglutarate dehydrogenase. As alpha ketoglutarate dehydrogenase controls the influx of glutamine/glutamate into the Krebs cycle, which is the major pathway for oxidative ATP generation in HeLa cells, the inactivation of alpha-ketoglutarate dehydrogenase was expectedly correlated with a net fall in glutamine/glutamate utilization. Furthermore, a simultaneous increase in glucose consumption and lactate production was observed, indicating that the cellular response to respiratory failure is to generate more ATP from glycolysis. In spite of this response, extensive depletion of ATP was observed. Thus, hyperoxia-induced growth inhibition and loss of clonogenicity seem to be due primarily to an impairment of mitochondrial energy metabolism resulting from inactivation of SH-group-containing flavoprotein enzymes localized at or near the inner mitochondrial membrane. These observations may be relevant for theories implicating loss of mitochondrial function as a prime factor in the aging process. PMID- 2233822 TI - The aging genome: determinant or target? Report of the EURAGE meeting on 'Genomic Instability and Aging', Nerja (Spain). PMID- 2233823 TI - International Commission for Protection Against Environmental Mutagens and Carcinogens. The possible involvement of somatic mutations in the development of atherosclerotic plaques. Report of ICPEMC Subcommittee 7/1. Conclusions and recommendations. PMID- 2233824 TI - International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/2. Shared risk factors for cancer and atherosclerosis--a review of the epidemiological evidence. AB - This paper reviews the epidemiological literature of relevance for the hypothesis that somatic mutation is involved in the formation of the atherosclerotic plaque. Assuming that somatic mutations are involved in atherogenesis, one would expect at least some of the risk factors for cancer and for atherosclerosis to be identical. Therefore, the review covers the correlated occurrence of cancer and atherosclerotic disease. Special interest is given to populations at high risk of cancer, including subpopulations with certain genetic diseases, and populations exposed to certain carcinogenic environmental agents including ionizing radiation, vinyl chloride monomer (VCM), arsenic, tobacco, and various industrial combustion effluents containing polycyclic aromatic hydrocarbons (PAHs). Exposure to combustion effluents from burning of tobacco or fuel is associated with an increased risk of cancer and atherosclerotic disease. Combustion effluents constitute a complex mixture of potentially hazardous agents, however, and the observed correlation of cancer and atherosclerosis among exposed persons cannot be unambiguously interpreted as evidence of a common etiology of the two groups of diseases. For ionizing radiation, arsenic, and VCM there is suggestive evidence that these agents possess an atherogenic effect beside their well-known carcinogenic properties. Both arsenic and VCM seem to have a specific affinity to the vascular bed causing various lesions including angiosarcomas and atherosclerotic plaques. Regarding ionizing radiation, the atherogenic effects seem to be localized to heavily irradiated fields. Beside the carcinogenic and atherogenic effects, exposure to arsenic, VCM, and ionizing radiation brings about an increase in the incidence of mutations and chromosomal aberrations. A theory involving somatic mutation in the pathogenesis of the atherosclerotic plaque could be consistent with the observed biological effects of ionizing radiation, arsenic, and VCM. The scant data from families with certain inherited diseases may also be consistent with an involvement of the genome in the pathogenesis of atherosclerosis. In conclusion, there is strong epidemiological evidence that several factors associated with an increased risk of cancer are also associated with an increased risk of atherosclerosis. PMID- 2233825 TI - International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Working Paper 7/1/3. Animal studies suggesting involvement of mutagen/carcinogen exposure in atherosclerosis. AB - It is very important to elucidate the causative agents of atherosclerosis because coronary heart disease and cerebrovascular disease are the main causes of death in the developed countries. The evidence for a monoclonal origin of atherosclerotic plaques in humans prompted the study of the involvement of mutagens/carcinogens in the development of atherosclerosis. Polycyclic hydrocarbons, including 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene, were shown to act as initiators and/or accelerators in atherosclerotic plaque formation in the chicken, pigeon and mouse. Radiation and oxygen radicals were also demonstrated to be involved in the development of atherosclerosis in animals. PMID- 2233826 TI - Evidence for an acetoxyarylamine as the ultimate mutagenic reactive intermediate of the carcinogenic aromatic amine 2,4-diaminotoluene. AB - 2,4-Diaminotoluene (2,4-DAT) is a mutagenic and hepatocarcinogenic aromatic amine, requiring metabolic activation. We have found that the mutagenic potency of 2,4-DAT in Salmonella TA98 is similar when activated by either Aroclor-1254 induced rat primary hepatocytes or 9000 x g supernatant. Previous work has demonstrated that 2,4-DAT is activated by cytochrome P450. The present report describes an investigation of the role of acetyltransferase in 2,4-DAT activation. Substitution of TA98 with the acetyltransferase-deficient strain TA98/1,8-DNP6 resulted in an approximately 90% decrease in the mutagenic potency for 2,4-DAT using S9 activation. The newly engineered acetyltransferase-enhanced Salmonella tester strain YG1024 (TA98(pYG219] demonstrated greatly enhanced sensitivity to the mutagenicity of 2,4-DAT. Inhibition of O-acetyltransferase activity, either with the selective acetyltransferase inhibitor thiolactomycin, or by competitive inhibition with an alternative substrate for the enzyme, reduced the mutagenicity of 2,4-DAT in this acetyltransferase-enhanced bacterial strain. From these data we conclude that following 2,4-DAT activation by N hydroxylation by cytochrome P450, the resulting hydroxylamino intermediate is further activated in the bacteria via O-acetylation to form the ultimate reactive intermediate, which is postulated to be 4-acetoxyamino-2-aminotoluene. PMID- 2233827 TI - Acute and subacute cytogenetic effects of the trihalomethanes on rat bone marrow cells in vivo. AB - The mutagenic effects of the trihalomethanes (THMs: chloroform, CHCl3; dichlorobromomethane, CHCl2Br; dibromochloromethane, CHClBr2; bromoform, CHBr3), found in chlorinated drinking water have been studied for their ability to induce chromosome aberrations (CA) in vivo in rat bone marrow cells. THMs were administered intraperitoneally (i.p. acute) and orally (subacute). Using a maximal dose of 1 mmole/kg body weight, positive results were noted for CHCl3, CHCl2Br, CHClBr2 and CHBr3 with i.p. treatment, and for CHCl3 and CHBr3 with oral treatment. The time-dependent increase in CA showed a maximum level at 12 h after i.p. injection and at 18 h after the fifth and last day of oral treatment. PMID- 2233828 TI - Evaluation of the mutagenic potential of endosulfan using the Salmonella/mammalian microsome assay. AB - The mutagenic potential of endosulfan, a polychlorinated insecticide, was assessed using the highly sensitive Salmonella tester strains TA97(a), TA98, TA100 and TA102. It exhibited a toxic effect at dose levels of 50 micrograms/plate and higher. Plate incorporation studies did not show mutagenic response with any of the tester strains used. A modification of the assay using a preincubation procedure showed mutagenic activity with and without metabolic activation with TA97(a) only. Increased toxicity was observed after addition of phenobarbital-induced S9 mix. PMID- 2233829 TI - Inhibitory effect of theophylline on repair of potentially lethal MMS-induced damages to DNA in V79 cells. AB - In a study of Chinese hamster V79 cells growing in the presence of sublethal concentrations of theophylline, we followed both the nature of DNA replication and the cells' response to toxic and DNA-damaging effects of methyl methanesulfonate (MMS). We found that cells cultured at low concentrations of theophylline (less than or equal to 0.3 mg/ml medium) showed deviations in the rate of DNA replication which, however, did not depress either the growth activity of the cells or their colony-forming ability. Considerable differences as against the controls appear in theophylline-cultured cells after treatment with MMS. Not only are they more sensitive to the toxic effects of this alkylating agent, but also their DNA synthesis is strikingly inhibited. More unrepaired lesions remain in parental DNA, and short fragments of daughter DNA, synthesized following cell treatment with MMS, are not elongated during a 2-h post-MMS treatment. Theophylline obviously belongs among agents inhibiting repair of potentially lethal MMS-induced DNA damages in Chinese hamster V79 cells. PMID- 2233830 TI - Absence of genotoxic activity of penbutolol in bacterial and mammalian cell screening systems. AB - The genotoxic potential of the beta-adrenergic blocker penbutolol was assessed using the Ames and HGPRT tests, unscheduled DNA synthesis (UDS) and alkaline elution assays. In the Ames test, penbutolol was tested for cytotoxicity and genotoxic activity in concentration ranges of 0.8-500 micrograms/plate and 0.1 125 micrograms/ml in the HGPRT, UDS and alkaline elution assays. In the Ames test penbutolol showed significant toxicity above 500 micrograms/plate. In the mammalian cells (V79) used for the HGPRT test and A459 cells used for alkaline elution and UDS assays, penbutolol was cytotoxic at concentrations above 30 micrograms/ml. In another series of experiments, male Wistar rats were treated i.p. with penbutolol (1, 10 and 100 mg/kg) and after 2 h liver nuclei were isolated and formation of single DNA-strand breaks was measured. The results of the present study demonstrate the absence of genotoxic activity of penbutolol in the 5 strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537 and TA1538) and in the strain of Escherichia coli WP2 uvrA in the presence or absence of metabolic activation. In V79 cells, penbutolol showed no mutagenic effects at the HGPRT locus in the presence or absence of metabolic activation. Additionally, no significant incorporation of [3H]thymidine into the DNA in the UDS test or formation of DNA-strand breaks in the alkaline elution assay was detected in the non-toxic concentration range of penbutolol with or without metabolic activation. Furthermore, penbutolol did not cause DNA damage in liver nuclei isolated from penbutolol-treated rats. PMID- 2233831 TI - Effect of alcohol sulfate, linear alkylbenzene sulfonate and natural soap on the development of fertilized eggs of the mouse in vitro. AB - Eggs from B6 x C3F1 female mice, which were fertilized in vitro with sperm from C3 x 101F1 male mice, were treated with synthetic surfactants, alcohol sulfate (AS) and linear alkylbenzene sulfonate (LAS), and natural soap for 1 h at the pronucleus stage, and then cultivated for 5 days. Eggs treated with AS or LAS at concentrations of less than 0.025% developed to the blastocyst stage as well as the untreated ones. At concentrations of AS or LAS higher than 0.03% no egg developed beyond the 1-cell stage. There appeared to be a threshold concentration between 0.025% and 0.03% of AS or LAS on the development of the mouse egg. However, natural soap had no effect on the development of the mouse egg up to 0.05%. When AS or LAS was applied to the culture medium throughout the cultivation of fertilized eggs for 5 days, there also appeared to be a threshold concentration between 0.01% and 0.025%, but not in the case of natural soap. The results provide additional support to our previous observations that AS and LAS can interrupt mouse pregnancy by killing fertilized eggs. PMID- 2233832 TI - Comparison of different plants in screening for Mn clastogenicity. AB - Cationic (MnSO4.H2O) and anionic (KMnO4) manganese salts in aqueous solutions enhanced the frequency of chromosomal aberrations including both chromosome- and chromatid-type breaks, gaps, translocations and spindle disturbances in different plant systems in vivo to a statistically significant level. The activity of the cationic salt was more drastic, particularly on the submerged plant studied (Vallisneria spiralis L.), on prolonged exposure, when compared with bulbs of Allium cepa L. and seeds of Pisum sativum L. PMID- 2233833 TI - Cytogenetic study for possible mutagenic activity induced by ice-nucleation bacteria or their metabolic products in human lymphocytes in vitro. AB - A means for eliminating ice-nucleation-active (INA) bacteria, the microorganisms responsible for frost damage to plants at mild freezing temperatures, is the use as competitors of other naturally occurring, non-nucleating strains. Inactive mutants (INA-) of INA bacteria have been produced by genetic or chemical methods and proposed for biological control of INA populations. Since, however, the application of these INA- mutants in the field may create health hazards to animals, we have studied the possible mutagenic activity of the INA- mutants by examining chromosome aberrations, sister-chromatid exchange (SCE) frequencies, and proliferation kinetics of human lymphocyte cultures. These cultures were treated with: (a) a naturally occurring INA- bacterium (p 767), (b) 2 parental strains (cit 7 and cit 13) of INA bacteria isolated from Citrus orchards, and (c) 2 INA- mutant strains (cit 7 del 1b and cit 13-12), produced, respectively, by chemical modification and by deletion of the corresponding parental strains. Neither whole bacteria nor infiltrates of bacterial growth media, in which toxic metabolic bacterial products might have been released, induced elevation of either chromosome aberrations and SCEs or a cell-division delay. Negative results were also obtained when sonicated bacteria were tested for possible intracellular mutagenic components. PMID- 2233834 TI - Cytogenetic analysis of mouse oocytes and one-cell zygotes as a potential assay for heritable germ cell aneuploidy. AB - Assays are needed for detecting chemically-induced aneuploidy, for investigating the mechanisms of aneuploidy production, and for obtaining heritable germ cell data that can be used to formulate human risk estimates. In this report, we describe the results of experiments designed to study aneuploidy in metaphase II (MII) oocytes induced by intraperitoneal (i.p.) or oral dosages of colchicine, and to investigate the proportion of aneuploid oocytes transmitted to one-cell (1C) zygotes following oral administration of colchicine immediately following HCG. The proportions (and percentages) of hyperploid MII oocytes were: 1/606 (0.2), 37/504 (7.3), 152/731 (20.8) and 75/319 (23.5) for control, 0.2, 0.3 and 0.4 mg/kg, respectively for i.p. administration of colchicine; and 3/216 (1.4), 8/539 (1.5), 81/511 (15.9), 71/398 (17.8) and 98/391 (25.1) for control, 1.0, 2.0, 3.0 and 4.0 mg/kg, respectively for oral administration of colchicine. The proportions of hyperploid 1C zygotes were 2/327 (0.6), 21/389 (5.4), 62/435 (14.3) and 69/438 (15.8) for control, 2.0, 3.0 and 4.0 mg/kg, respectively for oral colchicine. The proportions of hyperploid MII oocytes and 1C zygotes were significantly higher (Chi-square, P less than 0.01) at each i.p. or oral dose (except 1.0 mg/kg oral) than in the controls. The frequencies of hyperploidy induced by oral doses of colchicine were greater in MII oocytes than in 1C zygotes. We also found that the frequency of developmentally delayed and polyploid 1C zygotes increased with the dose of oral colchicine. Developmentally delayed zygotes contained male-derived chromosomes and female-derived fragmented pronuclei and pronuclei with decondensed chromosomes. These results indicate that higher doses of oral colchicine are needed to induce comparable levels of aneuploidy found after i.p. administration, and that aneuploid oocytes are fertilized and reach first cleavage metaphase. In addition, colchicine induces a spectrum of events including aneuploidy, polyploidy and developmentally delayed oocytes and zygotes. PMID- 2233835 TI - The effect of sampling time on radiation-induced translocation yield in spermatogonial stem cells of male mice, differing in chromosomal constitution and sexual activity. AB - We have investigated the frequency of reciprocal translocations in the first differentiating spermatogonia entering the first meiotic division after 2 x 2.5 Gy X-rays, given 24 h apart, as well as the development of this parameter in later stem-cell generations by studying multivalent configurations at the first meiotic division. Diakinesis-metaphase I cells were found for the first time between 30 and 40 days after irradiation. Subsequently, meiotic stages were sampled at 120, 180 and 280 days post irradiation. From day 40 post irradiation on, half of the males were allowed to impregnate females which enabled us to estimate the length of the post-irradiation sterile period, the development of litter size and the possible effect of sexual activity on the development of reciprocal translocation-containing stem cells. Half of the males were karyologically normal, the other half were homozygous for a reciprocal translocation (T/T) that affects testis weight and about halves sperm production. Irrespective of male karyotype, the first meiocytes had an induced translocation frequency of 9.00 +/- 2.56% (n = 8 males), followed by frequencies of 20.70 +/- 4.87% (n = 15) at 180 days and 20.20 +/- 4.30% (n = 20) at 280 days (males with and without mating behavior showing no difference). At 120 days post irradiation, +/+ males had a frequency of 14.59 +/- 2.97% irrespective of sexual activity. T/T males (120 days post irradiation) that had mated showed a frequency of 18.63 +/- 0.85% (n = 4) compared with 13.64 +/- 2.36% (n = 7) for those that had not. The observed rise of multivalent-carrying spermatocytes in time was highly significant. Notwithstanding the differences in testis weight and epididymal sperm count between the karyotypes, fertile matings occurred on average 72 days after irradiation, though with relatively wide margins. For the T/T karyotype, the first litter was statistically smaller than the subsequent litters. At 78 days post irradiation, testis weights were back in the subnormal range for both karyotypes and hardly improved in time. Restoration of fertility thus coincided with the period just prior to the return to subnormal testis weights. The first diakinesis-metaphase I cells precede those that are numerous enough to accomplish 'return to fertility' by about 2 weeks. Thus differentiation of stem-cell spermatogonia already follows a few days after irradiation. A pattern of spermatogonial cell divisions compatible with 'return to fertility' is only established some 2 weeks later. PMID- 2233836 TI - Induction of DNA-repair synthesis in primary rat hepatocytes by epoxides. AB - The genotoxicity of 10 epoxides was investigated in the UDS test with primary rat hepatocytes. The sensitivity of the assay was demonstrated using 2 acetylaminofluorence. The epoxides 1,2-epoxyoctane, 1,2-epoxydecane, epoxycyclooctane, epoxycyclododecane, (+)-limoneoxide, alpha-pinaneoxide, transstilbeneoxide, and cis-2,3-epoxysuccinic acid, which are known to be non mutagenic in the Ames test, as well as the bacterial mutagen, 1,2 epoxyphenoxypropane did not induce UDS in primary hepatocytes of the rat. However, a positive UDS response obtained with glycidyltrimethylammonium chloride showed that metabolic inactivation of the oxirane ring in hepatocytes is influenced by further structural substituents. PMID- 2233837 TI - Chirality-dependent DNA reactivity as the possible cause of the differential mutagenicity of the two components in an enantiomeric pair of epoxides. AB - Chemical compounds containing an epoxy group are very reactive substances and, in many cases, they therefore exhibit strong mutagenic properties. Very often such epoxides contain an asymmetric C atom and thus exist as racemic mixtures of optical isomers, the so-called R- and S-enantiomers. It is well known that in many cases a biological activity resides completely in one of the two enantiomeric forms of a molecule. Also, the R- and S-enantiomeric forms of epoxystyrene exhibit different mutagenic activities in Salmonella typhimurium TA100, although their chemical reactivity does not differ to a recognizable extent. Neither could the higher mutagenic activity of the R-epoxystyrene be attributed to a slower enzymatic hydrolysis reaction. Thus, the intrinsic potential for eliciting mutagenic responses may not be the same for the two enantiomers, as there is evidence of qualitative differences in the binding to DNA, pointing strongly to an intrinsic difference in mutagenic activity of the two enantiomers. PMID- 2233838 TI - Evaluation of the mutagenicity of combustion particles from several common biomass fuels in the Ames/Salmonella microsome test. AB - We have evaluated the mutagenicity of dichloromethane extracts of combustion particles from several biomass fuels that are commonly used in developing countries in Salmonella strains TA98 +/- S9 and TA100 +/- S9. Combustion-particle extracts from dried cow dung and crop residue exhibited mutagenic potencies similar to wood-smoke extracts (0.0-1.0 rev./microgram extract). However, extracts from coconut-shell-smoke particles showed relatively potent direct acting mutagenicity (1.6 rev./micrograms, TA98-S9). Results from testing this sample in nitroreductase- and acetylase- deficient strains TA98NR and TA98 (1,8 DNP-6) revealed no contribution from nitroarenes. PMID- 2233840 TI - Methyl vinyl sulphone: a new class of Michael-type genotoxin. AB - Methyl vinyl sulphone (MVS) is a labile, Michael-reactive chemical, similar in structure to acrylamide (AA). Given that acrylamide is a reference mammalian mutagen and a rodent carcinogen, studies were undertaken to evaluate the potential genotoxicity of MVS. In common with AA, MVS was non-mutagenic to Salmonella but active as an aneugen to cultured mammalian cells. It is concluded that vinyl sulphones should be regarded as representative of a new class of genotoxic chemical whose mode of action is probably primarily dependent upon Michael reactivity to proteins. PMID- 2233839 TI - Role of sulfation and acetylation in the activation of 2-hydroxyamino-1-methyl-6 phenylimidazo[4,5-b]pyridine to intermediates which bind DNA. AB - Mutagenic activity associated with amino-imidazoazaarene food-derived mutagens such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) appears to be dependent upon N-hydroxylation, though additional metabolic pathways may be involved in the production of the ultimate reactive intermediate which covalently binds DNA. We have evaluated the ability of 2-hydroxyamino-1-methyl-6 phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP) to bind DNA in vitro and have determined which secondary metabolic pathways are involved in the production of electrophilic intermediates. Incubation of DNA with 10 microM N-hydroxy-PhIP alone or with mouse-liver cytosol did not result in detectable adduct formation. Addition of 3'-phosphoadenosine 5'-phosphosulfate or acetyl coenzyme A to cytosolic incubations containing N-hydroxy-PhIP resulted in DNA adducts which could be detected by 32P-postlabeling at levels of 594 and 30 fmoles/micrograms DNA, respectively. Addition of 3'-phosphoadenosine 5'-phosphosulfate and to a lesser extent acetyl coenzyme A to cytosolic incubations also increased the rate of degradation of the unstable N-hydroxy-PhIP intermediate. These data suggest that both sulfation- and acetylation-dependent metabolic pathways may be important in the mammalian genotoxic actions of PhIP. PMID- 2233841 TI - Growth delay and filamentation of Escherichia coli wild-type and Rec A cells in response to hexavalent chromium and other metal compounds. PMID- 2233842 TI - Severe chromosomal damage in mammalian cells induced by pulse labeling with small amounts of [3H]thymidine. AB - Pulse labeling of cultured mammalian cells with tritiated thymidine ([3H]TdR; different specific activities, 2-47 Ci/mmole) for 30 min at low concentrations of radioactivity (0.2-2 microCi/ml) causes an unusually high degree of chromosomal aberrations which becomes fully evident in the cohort of cells analyzed 8 h later. The effect depends on the total amount of radioactivity. In HeLa cells up to 93% aberrant metaphases with up to 3.6 aberrations per metaphase were observed; in CHO cells the corresponding figures are 62% aberrant metaphases with 1 aberration per metaphase. The results may be valuable (i) for users of the pulse-labeling technique for analysis of cell-cycle kinetics, as this shows the technique as such may delay the labeled cohort of cells and therefore interferes with the matter under study and (ii) for risk assessment. PMID- 2233843 TI - Effects of in vivo exposure to antineoplastic drugs on DNA repair and replication in human lymphocytes. AB - In peripheral blood lymphocytes of 12 nurses and 3 patients exposed to antineoplastic drugs we determined the ability to repair DNA after UV irradiation and DNA replicative synthesis after stimulation by PHA. In nurses the levels of unscheduled DNA synthesis and DNA replication were not different than in a control group, whereas in patients significant changes were observed during and after chemotherapy in the level of both types of DNA synthesis. PMID- 2233844 TI - Inactivity of copper sulphate in a mouse bone-marrow micronucleus assay. PMID- 2233845 TI - Activity of urethane and N,N-dimethylurethane in the mouse bone-marrow micronucleus assay: equivalence of oral and intraperitoneal routes of exposure. AB - Urethane is shown to be active in the mouse bone-marrow micronucleus assay when administered as a single dose by either gavage or intraperitoneal injection. The magnitude of the response using the two routes was not statistically significantly different. N,N-Dimethylurethane (DMU) is shown to be mutagenic to Salmonella and active in the bone-marrow micronucleus assay by both routes of administration. The activity of DMU in the bone marrow precludes elimination of ethanol, yielding cyanate ion, as an explanation for the micronucleus-inducing activity of urethane. PMID- 2233846 TI - Multiple-pulse stimulation and dantrolene in malignant hyperthermia. AB - A potentially fatal condition, yet preventable, malignant hyperthermia (MH) lacks a satisfactory noninvasive diagnostic test. Studying the effects of intravenous dantrolene (3 mg/kg) on electrically stimulated skeletal muscle, we found that this approach does not conclusively distinguish between normal humans and those susceptible to malignant hyperthermia but nonetheless yielded important information about the action of dantrolene in man and in MH. Supramaximal single- and multiple-pulse stimulation of the common peroneal nerve produced stable torque responses of the dorsiflexor muscles (monitored in vivo), which dantrolene suppressed. With the multiple-pulse stimulation (5-6 pulses) this torque suppression was significantly less in MH-susceptible subjects than in control subjects. This distinction, also observed in MH swine, confirms this animal as a good model for human MH. That dantrolene's effect in MH can be more completely reversed with high frequency stimulation is intriguing; presumably, excitation contraction coupling differs in MH and normal muscle. PMID- 2233847 TI - Recording and physical characteristics of disposable concentric needle EMG electrodes. AB - There is currently considerable interest in using disposable concentric needle (CN) electrodes for clinical electromyography (EMG). To determine how these electrodes compare with reusable CN electrodes, we have compared signals recorded by these two electrode types from the same muscle in normal subjects. We also made similar recordings with two groups of reusable electrodes. There was no difference in the features of motor unit action potentials (MUAPs) recorded by the two groups of reusable electrodes. Disposable electrodes performed satisfactorily in conventional EMG examination. However, compared to reusable electrodes, the disposable electrodes recorded MUAPs with smaller amplitude and area but with the same area:amplitude ratio and MUAP duration. The physical and electrical properties of the CNE groups were also investigated. Disposable electrodes had lower electrical resistance and greater capacitance than reusable electrodes when measurements were made in saline. Photomicrographs showed that the disposable electrodes had smaller recording surfaces and that the central wire was frequently eccentric in the cannula. The differences in electrical recording characteristics could be due to differences in the size of the recording surface, eccentric placement of the central wire in the cannula or differences in the metal used for the central wire. We conclude that electrical and physical testing may not predict the recording characteristics of needle electrodes. Electrophysiologic testing is necessary to determine how EMG signals recorded by new types of electrodes compare with those recorded by currently used electrodes. PMID- 2233848 TI - Concurrence of malignant hyperthermia and congenital abnormalities. AB - Two children about to undergo corrective surgery were required to be investigated for malignant hyperthermia (MH). These investigations arose out of concern by the anesthetist who had obtained a history of unexplained pyrexial reactions to anaesthetic in other members of the family. Because over the years we have encountered several children with multiple congenital abnormalities who have been found to be susceptible to MH, we stressed the advisability of biopsying not only the patient but also the patient's parents. Positive responses for MH were obtained in the patients and in one of the parents on each occasion. The hypothesis of intrauterine MH with its pharmacogenetic propensity for heat production is considered as a possible etiological factor which may cause abnormalities of a congenital nature. PMID- 2233849 TI - Isometric features of orthostatic tremor: an electromyographic analysis. AB - A patient is described with "orthostatic" tremor. Electromyography revealed tremor bursts of 15 Hz in the lower extremities while standing and with isometric activation of the muscles, but the bursts disappeared with isotonic activation of muscles. Similar tremor was recorded in the arms with isometric, but not isotonic activation. Review of previously reported cases confirms these findings. The clinical and electrophysiologic features of this tremor distinguish it from other recognized forms of tremor. PMID- 2233850 TI - Soleus-specific myopathy induced by passive stretching under local tetanus. AB - Twenty-four adult albino rats were injected with tetanus toxin into the right gastrocnemius muscle and then subjected to sustained dorsiflexion of the right ankle joint for 2 to 14 days. Histologic examinations of the soleus after this procedure showed myopathic changes, characterized by variations in fiber diameters, myonecrosis with opaque fibers, interstitial fibrosis, and small groups of regenerated fibers. Electron microscopy revealed derangement of T tubules immediately adjacent to the sarcolemma in the early degenerative stage. The size and wet weight of soleus increased compared to that of the control side between 2 and 5 days post-tetanus. Serum GOT, LDH, and creatine kinase (CK) levels were elevated especially in the early degenerative stages. Peri- and endomysial fibrosis developed gradually from about 3 days post-tetanus. Pathomechanisms inducing these changes were discussed. PMID- 2233851 TI - Measurement of the amplitude of the EMG envelope. AB - When the force of muscle contraction is increased, the amplitude of the EMG envelope (ENAMP) increases. The ENAMP is usually assessed subjectively and its value in EMG analysis has been established. In this article we describe a method to make automatic measurements of the ENAMP. This method was tested on recordings of the EMG interference pattern (IP) from the biceps muscle of normal subjects. Normal values of this feature in the biceps muscle are described. There was a good concordance between the ENAMP measurements made by subjective assessment and by automatic analysis and the ENAMP values correlated strongly with a previously described feature of the IP called the upper centile amplitude. We infer that ENAMP is a robust feature of the IP that reflects the amplitude of the largest MUAP in the IP. PMID- 2233852 TI - Central changes in hypothyroid myopathy: a case report. AB - A muscle biopsy from a patient with hypothyroid myopathy showed striking central changes. "Cores" were seen in most type 1 fibers with oxidative enzyme preparations. Electron microscopy of these areas revealed Z disc streaming, myofilament disruption, and absent mitochondria. The myopathy rapidly improved with thyroxine treatment. This biopsy is of interest, as numerous "cores" have not previously been reported in hypothyroid myopathy. PMID- 2233853 TI - A comparison of magnetic and electrical stimulation of peripheral nerves. AB - We compared magnetic stimulation using different coil designs (2 rounded coils and a butterfly-prototype coil) with electrical stimulation of the median and ulnar nerves in 5 normal subjects. Using magnetic stimulation we were able to record technically satisfactory maximal sensory and motor responses only with the butterfly coil. Submaximal electrical stimuli preferentially activated sensory rather than motor axons, but submaximal magnetic stimuli did not. The onset latency, amplitude, area and duration of responses elicited electrically or magnetically with the butterfly coil during routine sensory and motor nerve conduction studies were similar, and motor and sensory conduction velocities were comparable when studied over long segments of nerve. However, the motor conduction velocities with magnetic and electrical stimulation differed by as much as 18 m/sec in the across-elbow segment of ulnar nerve. Thus, recent developments in magnetic stimulator design have improved the focality of the stimulus, but the present butterfly coil design cannot replace electrical stimulation for the detection of focal changes in nerve conduction velocity at common entrapment sites, such as in the across-elbow segment of the ulnar nerve. PMID- 2233854 TI - Quantitative electromyography in polymyositis: a reappraisal. AB - Manual analysis of motor unit action potentials (MUAPs) was performed in 33 patients with polymyositis of whom 16 were studied in the acute stage and 17 in the chronic stage. Contrary to common description of "myopathic potentials" as being of low amplitude, short duration, and polyphasic shape, the quantitated study revealed no difference as to amplitude of short duration MUAPs in patients and normal subjects though short-duration MUAP and short duration polyphasic potentials were 4 and 3 times, respectively, more common in patients than in controls. Although the mean duration of MUAPs usually was significantly shorter in polymyositis than in controls, the average scatter of MUAPs duration was the same in the 2 groups. The average incidence of polyphasic MUAPs was 4 times higher in patients than in controls, as was the incidence of those of long duration. To avoid misinterpretation of EMG findings due to an excess of polyphasic MUAPs, a greater number of individual potentials than usually recommended should be collected allowing a valid estimate of the mean duration of MUAPs of simple configuration. PMID- 2233855 TI - Abstracts of poster and platform presentations: Fourth International Conference on Computerized and Quantitative EMG. Mainz, Germany, September 13-15, 1990. PMID- 2233856 TI - Fibrillation potentials and muscle fiber types. PMID- 2233857 TI - Myoclonus (nocturnus) PMID- 2233858 TI - Sensitivity for detecting fibrillation potentials: a comparison between concentric and monopolar needle electrodes. AB - The sensitivity of monopolar and concentric electrodes for detecting fibrillation potentials (FP) has never been formally compared. We studied 35 muscles with FP, sampling 20 sites each with concentric and monopolar needles. The concentric needle identified 0.88 +/- 3.44 (mean +/- standard deviation) more sites with spontaneous activity. Although statistically significant (Wilcoxon signed rank test P less than .03), this difference in sensitivity did not appreciably affect diagnostic interpretation. Subjects described the concentric needles as more painful. Needle insertions in 25 other muscles demonstrated that needle movement generated the majority of FP. We suggest that the increased tissue injury caused by concentric needles may account for both their increased sensitivity and discomfort. PMID- 2233859 TI - Time course of sprouting during muscle reinnervation in vitamin E-deficient rats. AB - A typical aspect of motoneuron plasticity is the sprouting which occurs during muscle reinnervation, resulting in a transitory multiple innervation of the muscle cells. In order to verify the effect of a decreased protection from free radical attack on the sprouting, the multiple innervation in the extensor digitorum longus muscle, following sciatic nerve crush and regeneration, was studied in vitamin E-deficient rats. Thus, the innervated end-plates and the end plates with multiple innervation were studied with histochemical and electrophysiological techniques. The percentage of innervated end-plates was similar in both groups at 30 as well as at 60 days after nerve crush. Nevertheless, multiple innervation was found in a larger part of the muscle and it lasted longer in the deficient rats. This finding is discussed in relation to some of the major hypotheses of sprouting; it may be relevant in the treatment of some lesions of peripheral nerve. PMID- 2233860 TI - A review of techniques employed to estimate the number of motor units in a muscle. AB - Being the smallest functional units under neural control, motor units play an integral role in muscle physiology. However, at the present time, there does not exist any widely accepted technique for quantifying or estimating the number of motor units in a muscle. Specifically, the existing techniques are the increment counting technique, a technique based on spike-triggered averaging, and a macro EMG based technique which vary in invasiveness from noninvasive to highly invasive, respectively. We discuss each of these techniques, along with their associated shortcomings, in detail. PMID- 2233861 TI - Spatial dispersion of magnetic stimulation in peripheral nerves. AB - To assess the longitudinal dispersion of the stimulus induced by the magnetic coil, collision experiments were performed in seven normal ulnar nerves. A supramaximal electrical stimulus S1 was delivered at the wrist, and followed by a supramaximal stimulus S2 in the upper arm, which was either electrical (electrical collision studies), or magnetic (magnetic collision studies). The interstimulus interval was varied by 0.2 msec increments from the time of complete cancellation of the S2 evoked motor response onwards, to include the entire span of recovery of that compound motor action potential. Collision curves were obtained for both magnetic and electrical stimuli by plotting the amplitude of the motor response elicited by S2 as a function of the interstimulus interval. In all seven normal ulnar nerves, comparison of the collision curves showed that the S2 evoked motor response is restored significantly more slowly when magnetic stimulation is used. This finding is best explained by longitudinal dispersion of the stimulus induced by the magnetic coil relative to conventional electrical stimulation, the large fibers being stimulated further away from the coil than the small ones. This interpretation is confirmed by the findings obtained with the same method in two cases of ulnar neuropathy, and by comparison of different intensities of magnetic stimulation. PMID- 2233863 TI - International symposium on peripheral nerve regeneration. Washington, DC, September 17, 1989. Proceedings. PMID- 2233862 TI - AAEM minimonograph #35: Clinical experience with transcranial magnetic stimulation. AB - We elicited motor evoked potentials (MEPs) using transcortical magnetic stimulation in 150 control subjects aged 14 to 85 years and 275 patients with a variety of diseases. There were no significant side effects. Cortex-to-target muscle latencies measured 20.2 +/- 1.6 ms (thenar), 14.2 +/- 1.7 ms (extensor digitorum communis), 9.4 +/- 1.7 ms (biceps), and 27.2 +/- 2.9 ms (tibialis anterior). Central motor delay between the cortex and the C-7 and L-5 measured 6.7 +/- 1.2 ms and 13.1 +/- 3.8 ms, respectively. Mean spinal cord motor conduction velocity measured 65.4 m/s. MEP amplitude expressed as a percentage of the maximum M wave was never less than 20% of the M wave. A value of less than 10% is considered abnormal. MEP latency increases linearly with age and central motor delay is longer in older subjects. Compound muscle action potentials and absolute MEP amplitudes decreased linearly with age. In multiple sclerosis (MS), MEP latency and central delay were often very prolonged. The MEP was more sensitive than the SEP in MS. In amyotrophic lateral sclerosis, MEP latencies were only modestly prolonged; the characteristic abnormality was reduced amplitude. When pseudobulbar features predominated MEPs were often absent. The MEP was of normal latency in Parkinson's disease, but age-related amplitude was often increased. MEP latency and amplitude were normal in Huntington's disease. Abnormal MEPs persisted several months after stroke despite good functional recovery. The MEP could be used to advantage to demonstrate proximal conduction slowing and block in demyelinating neuropathies. In plexopathy, ability to elicit an MEP several days after onset of paresis was good evidence of neuronal continuity in motor fibers. PMID- 2233864 TI - The anatomy and physiology of nerve injury. AB - Nerves have a structure of considerable complexity with features of special relevance to nerve injury and nerve regeneration. These include variations in the cross-sectional areas devoted to fascicular and epineurial tissue, the fascicular redistribution and mixing of different branch fibers brought about by fascicular plexuses, and the numbers of nerve fibers representing individual branches. The elasticity and tensile strength of nerve trunks and their capacity to resist traction deformation reside in the fascicular tissue, while the epineurium provides a protective cushion against compression. The microstructure of nerve trunks provides the basis for a classification of nerve injuries into five degrees of severity with partial and mixed types--each with a clearly defined pathology and distinguishing clinical features. Following a transection injury, changes occur in the severed axons, endoneurial tubes, fasciculi, and nerve trunk. The type of injury and the nature of these changes determine the outcome of axon regeneration. PMID- 2233865 TI - Enhancement of peripheral nerve regeneration. AB - Numerous factors external to the nerve cell can support and enhance nerve regeneration after injury. The definition of these factors and the elucidation of their mechanisms of action are the central goals of much contemporary neurobiologic research. This research will hopefully lead to the discovery of factors that will prove to be therapeutically beneficial for patients with either peripheral nervous system (PNS) injury or central nervous system (CNS) injury. This article reviews the biology of the regeneration response of the nerve to injury and discusses many of the factors that enhance nerve growth. Finally, the nerve guide or nerve regeneration chamber model for the evaluation of putative nerve regeneration enhancing agents in vivo is also discussed. PMID- 2233866 TI - Aberrant reinnervation. AB - Although great emphasis is placed on providing a satisfactory conduit for regeneration of peripheral axons after nerve repair, the quality of functional restoration is influenced as much by the quality as the quantity of axonal regeneration. Misdirected regeneration is so commonly encountered that motor axons appear to enter and regenerate to muscles in an almost random manner. Thus, when there are several choices, as usually is the case with more proximal nerve or plexus repairs, misdirected reinnervation accounts in many incidences for a poor quality of functional restoration. The regenerative capacities of type I and type II motor axons appear to differ. Proprioceptors and other sensory axons have been shown to reinnervate inappropriate end organs. Consequently, deranged central reflex modulation and disturbed orderly recruitment of motor units according to the size principle also contributes to this problem. Central re education or adaptation to misdirected regeneration does not occur to any appreciable extent. PMID- 2233867 TI - Fibrillation potential amplitude and muscle atrophy following peripheral nerve injury. AB - Maximum peak-to-peak fibrillation potential amplitude was measured in 69 subjects between 7 days and 10 1/2 years post complete or partial peripheral nerve injury. Mean amplitude during the first 2 months was 612 muV; third and fourth months 512 muV, fifth and sixth months 320 muV. After the first year, no population of fibrillation potentials greater than 100 muV was recorded. The sciatic nerve was sectioned in 13 guinea pigs and animals studied up to 17 weeks. Fibrillation potential amplitude in gastrocnemius muscles declined paralleling that in humans. By the end of the study, type I fibers had lost almost half of their initial diameter and type II fibers had atrophied more than twice this amount. Fibrillation potential amplitude may be useful in estimating the time post nerve injury and appears to correlate with the surface area and fiber diameter of a type I muscle fiber. PMID- 2233868 TI - Quantitative clinical electrophysiology in the evaluation of nerve injury and regeneration. AB - Neuromuscular electrophysiological techniques can provide clinically important information about the localization, severity, and pathophysiology of peripheral nerve injuries, and about the progress of reinnervation. The relevant variables for study are compound nerve and muscle action potentials, motor unit action potentials, and denervation potentials. Available methods do not permit meaningful quantitation of regeneration. Newer methods under development attempt to estimate the number of motor units in a muscle and the number of axons in a nerve. PMID- 2233869 TI - Single fiber EMG evaluation in denervation and reinnervation. AB - SFEMG can be used to follow the course of reinnervation. The parameters of fiber density, mean jitter and percent blocking must each be followed and related to the type of injury to determine the stage of reinnervation. The few reported cases in the literature of SFEMG recordings followed over time after nerve compromise are reviewed and an additional case is presented by the author. Mean jitter values can return to normal approximately 1 1/2 years postonset of reinnervation. Some individual recordings may remain abnormal permanently. PMID- 2233870 TI - Critical review of gangliosides and thyrotropin-releasing hormone in peripheral neuromuscular diseases. AB - The lack of effective therapy for many of the chronic neuromuscular diseases such as amyotrophic lateral sclerosis, hereditary motor sensory neuropathy (Charcot Marie-Tooth disease), spinocerebellar degenerations and idiopathic polyneuropathy has led to a search for substances that may stimulate peripheral nerve regeneration. Two such agents that have been proposed are gangliosides (mixed purified bovine brain gangliosides, Cronassial) and thyrotropin releasing factor (TRH). Studies on both of these agents were initially reported with enthusiasm to be successful, but later double-blind controlled studies have failed to confirm these findings. This review provides critical analysis of the designs of studies of potentially effective agents in chronic neuromuscular diseases, and emphasizes the power of the placebo response, and the importance of designing placebos which are indistinguishable from the trial medication other than in the active effect. PMID- 2233871 TI - Surgical repair of peripheral nerve injury. AB - Magnification, use of fine interfascicular grafts for repair, and development of intraoperative electrophysiologic measurements of function have had a substantial impact on this field in the last 10 to 20 years. Basic surgical principles established during and since World War II remain the foundation for surgical repair of peripheral nerve injury but have been complemented nicely by these more recent advances. Selection of patients for surgery, as well as the timing of such, has been reviewed with emphasis on the differences between suspected transections and lesions in continuity, as well as comments on serious peripheral entrapments and tumors affecting nerve. The importance of not only preoperative electromyographic studies but also the intraoperative use of stimulation and stimulation and recording of nerve action potentials (NAPs) for lesions in continuity has been stressed. Operative techniques such as neurolysis, NAP recordings, suture, split repair, and interfascicular graft repair have been reviewed and some commentary on results provided. There has been a gradual evolution of centers in this country and abroad for care of the more serious surgical nerve problems. It is anticipated that in the future, such centers will be able to provide improved data concerning results with civilian nerve injuries. PMID- 2233872 TI - Abstracts of poster and platform presentations: 37th annual meeting. American Association of Electrodiagnostic Medicine. Chicago, Illinois, September 7-8, 1990. PMID- 2233873 TI - Testing of therapeutic interventions in humans. PMID- 2233874 TI - Evaluating muscle strength and function. Proceedings of a workshop. Nashville, Tennessee, April 27-28, 1989. PMID- 2233875 TI - Preliminary observations on the reliability of the DCN-SMA Study Group methodology. Dallas-Cincinnati-Newington Spinal Muscular Atrophy (DCN-SMA) Study Group. PMID- 2233876 TI - Sensitivity of the DCN-SMA Study Group methodology. Dallas-Cincinnati-Newington Spinal Muscular Atrophy (DCN-SMA) Study Group. PMID- 2233877 TI - Manual muscle testing. PMID- 2233878 TI - Biomechanical muscle performance. PMID- 2233879 TI - Functional testing. AB - Functional testing is useful to monitor the natural history of several neuromuscular disorders, and to measure the efficacy of therapeutic agents in clinical trials. A major limitation of functional testing is that a single test is often not appropriate throughout all stages of disease. The same limitation holds true for other measurements of disease progression. MMT and quantitative myometry become technically difficult to perform and lack sensitivity to disease progression at some stages in the course of DMD, ALS, and spinal muscular atrophy. Other limitations of functional testing are its lack of sensitivity to detect a subtle improvement or decline in muscle strength, and the difficulty of applying standard statistical methods to analyze disease progression or therapeutic efficacy. The advantages of functional testing outweigh the limitations. Function testing uses daily activities to monitor disease progression. Patient's appreciate improvements in function more readily than improvements in muscle strength. Functional testing is easily standardized and is reliable. It can be performed, with little or no expense, in almost any clinical setting. The primary challenge for investigators who wish to incorporate functional tests is to identify functional tests that best measure the natural history of the specific disease under investigation. Further, functional testing allows the clinician to provide an educated guess on the likely future course of disease. PMID- 2233880 TI - Clinical trials in neuromuscular disease. PMID- 2233881 TI - The use of pulmonary function testing as a quantitative measurement for therapeutic trials. PMID- 2233882 TI - Fatigue testing. PMID- 2233883 TI - Introductory comments on disease-specific tests. PMID- 2233884 TI - Specific tests for polymyositis. PMID- 2233885 TI - Statistical considerations in clinical trials. PMID- 2233887 TI - Modeling of time-strength relationships. PMID- 2233886 TI - Statistical considerations in the study of spinal muscular atrophy. Dallas Cincinnati-Newington Spinal Muscular Atrophy (DCN-SMA) Study Group. PMID- 2233888 TI - Isokinetic dynamometry. AB - Quantitative muscle performance assessments require standardized protocols and logical explication of raw scores, regardless of technique used. A very expensive dynamometer is not a substitute for competent personnel carrying out strength assessments, and well-thought-out interpretations of the data. PMID- 2233889 TI - A methodology to measure the strength of SMA patients. Dallas-Cincinnati Newington Spinal Muscular Atrophy (DCN-SMA) Study Group. PMID- 2233890 TI - Osteomyelitis due to Cryptococcus neoformans in advanced age. Case report and review of literature. AB - In an 84-year-old man cryptococcosis with a pronounced osteomyelitic course (involvement of a rib, two thoracic vertebrae, the sacrum and a femur) was diagnosed histologically post mortem, thus directing attention to cryptococcosis in advanced age. The presumptive chronic course of the Cryptococcus neoformans (Cr. n.) infection in this patient was ascribed to chronic kidney failure, diabetes mellitus and chronic obstructive lung disease. Special reference is made to the mycological and radiological diagnosis of cryptococcosis of the bones as well as to its pathogenesis, therapy and epidemiology. PMID- 2233891 TI - Experimental dermatophytosis in nude guinea pigs compared with infections in Pirbright White animals. AB - With this investigation we wanted to compare the suitability of two different strains of guinea pigs to evaluate topical antifungals after experimental Trichophyton mentagrophytes infection. The "hairless"-strain was compared with the hairy Pirbright White strain. The infection areas were treated with a skin retention test (application before infection) and two sets of therapy tests (application after infection). In the retention test the different antimycotic compounds led to better gradations. Also, in the two sets of therapy tests the gradations among the compounds were more clearly and more comparable to published results of clinical trials. In the histological investigations the infections in the "hairless" animals developed in a way which is known from dermatophytoses in human skin. In the Pirbright White strain, however, due to the adjacent hair roots, a marked inflammatory reaction of the tissue persisted for 3 weeks which is not observed on human skin of the trunk and extremities. We, therefore, consider the "hairless" strain of guinea pigs to be more suitable than hairy animals for the comparison of topical antimycotics. PMID- 2233892 TI - Rilopirox--a new hydroxypyridone antifungal with fungicidal properties. AB - Rilopirox, 6-[[p-chlorophenoxy)phenoxy]methyl]-1hydroxy-4-methyl-2(1H)-pyrido ne, is a new fungicidal antimycotic with very low water solubility. It was designed to meet the demand for an intravaginal antifungal with a long skin retention time and a strong killing effect on pathogenic yeasts. In addition, it inhibits all common fungal pathogens in the range 0.98 to 15.6 micrograms/ml. Fungicidal rates vis-a-vis Trichophyton mentagrophytes and Candida albicans under proliferative and non-proliferative conditions are higher than those achieved with common azole and allylamine antifungals. Rilopirox is affected by Fe3+ ions and high concentrations of human serum owing to its chelating activity. The peptone source is of utmost importance to the inhibitory activity of rilopirox whereas the pH value seems to be unimportant so long as it is within the range 5-8.5. Rilopirox appears to meet the demand for an intravaginal antifungal as a result of its very low water solubility of 50 ng/ml and its immediate fungicidal action even under non-proliferative conditions. PMID- 2233893 TI - In vitro activities of polyene and imidazole antifungal agents against unusual opportunistic fungal pathogens. AB - Guidelines for the treatment of infections caused by unusual opportunistic fungi are limited and available in vitro data are scanty. In vitro susceptibility tests, employing an agar dilution procedure, were performed with amphotericin B (AMB), natamycin (NTC), itraconazole (ICZ), and ketoconazole (KTZ). Two media were used: Kimmig's agar (KA) and Yeast Morphology Agar (YMA). Fungi tested included isolates (n) of Acremonium spp. (10), Cunninghamella spp. (6), Fusarium spp. (18), Pseudallescheria boydii (14), and Trichosporon beigelii (5). All Acremonium and Cunninghamella isolates were susceptible to NTC (MIC less than or equal to 4 micrograms/ml) but many appeared to be resistant to AMB, (MIC greater than or equal to 32 micrograms/ml), KTZ and ICZ (MIC greater than or equal to 128 micrograms/ml). Most isolates of Fusarium spp. were susceptible to both AMB and NTC (MIC90 = 4 micrograms/ml); one isolate was cross-resistant to both polyenes (MIC greater than 32 micrograms/ml). Only two of 18 Fusarium isolates appeared susceptible to the imidazoles (MIC less than or equal to 4 micrograms/ml); the remaining isolates exhibited high MICs (greater than or equal to 64 micrograms/ml). All 14 isolates of P. boydii were susceptible to NTC (MIC less than or equal to 4 micrograms/ml) but four appeared to be resistant to AMB (MIC greater than or equal to 32 micrograms/ml). Most isolates of P. boydii were susceptible to both KTZ (MIC less than or equal to 4 micrograms/ml) and ICZ (MIC less than or equal to 16 micrograms/ml) but two isolates appeared to be resistant (MIC greater than or equal to 16 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2233894 TI - Structure of a telomeric expression site for variant specific surface antigens in Trypanosoma brucei. AB - We have studied the organization of the expression site, in which most chromosome internal variant-specific surface glycoprotein (VSG) genes of Trypanosoma brucei strain 427 are expressed (the dominant expression site) and compared it to the previously characterized VSG 221 expression site. With the exception of a 500 bp segment and a VSG pseudogene, which are absent from the dominant expression site, overall all major sequence elements of the two sites are organized similarly, as judged from their relative mapping positions by UV inactivation of transcription. Transcription is insensitive to 1 mg alpha-amanitin per ml, a characteristic property of VSG gene expression sites analyzed thus far. The sequence elements of the dominant expression site include at least one other expressed gene of unknown function and homologues of at least two other open reading frames. The large internal duplication of the 60-kb 221 expression site appear to be missing from the dominant site, resulting in a shorter, 40-kb transcription unit. As judged from its relative sensitivity to UV inactivation of transcription, a subsidiary promoter, identified by other methods in the dominant expression site appears fully dependent for its activity on the promoter located 40 kb upstream of the VSG gene. We conclude that all VSG gene expression sites may be similarly organized as large polygenic transcription units. PMID- 2233895 TI - A 31P nuclear magnetic resonance study of Crithidia luciliae. AB - 31P NMR has been used to observe phosphorus-containing compounds in both perchloric acid and KOH extracts and in whole cell suspensions of Crithidia luciliae. Cells were grown in Bone and Steinert medium, or in a modified RPMI culture medium and harvested after about 72 h in mid- to late log phase. 31P NMR spectra of the perchloric acid extracts indicated that 3-phosphoglycerate, which is normally at low concentrations in most cells, was the dominant phosphorus containing compound in the sugar phosphate region. 3-Phosphoglycerate is the end product of glycosomal glycolysis and our finding is consistent with previous observations of the failure to detect prior glycolytic intermediates. Other metabolites observed were ATP, ADP, NAD(P)+, phosphoenolpyruvate and low molecular weight polyphosphates (PPn, n less than 20). The presence of high molecular-weight polyphosphates was established by spectra recorded on extracts obtained through subsequent treatment of the insoluble fraction with KOH. 31P NMR experiments on whole cells indicated that the average main internal pH of cells in late-log growth phase was approx. pH 7.2 +/- 0.1, using the orthophosphate resonance as an indicator. The cells responded to the addition of glucose (final concentration approx. 35 mM) with a decrease in pH, both internal (delta pH = 0.9 (55 min)-1) and external (delta pH = -1.3 (15 min)-1). Polyphosphates and ATP could not be observed in whole cell experiments, although perchloric acid extracts of identically treated cells showed no significant depletion of these compounds. PMID- 2233896 TI - Ca2+ transport in digitonin-permeabilized trypanosomatids. AB - The use of digitonin to permeabilize Leishmania mexicana mexicana, Leishmania agamae, and Crithidia fasciculata plasma membranes enabled us to study Ca2+ transport in situ. The present results show that the mitochondria of these trypanosomatids are able to build up and retain a membrane potential as indicated by a tetraphenylphosphonium-sensitive electrode. Ca2+ uptake caused membrane depolarization compatible with the existence of an electrogenically mediated Ca2+ transport mechanism in these mitochondria. Ca2+ uptake was partially inhibited by ruthenium red, almost totally inhibited by carbonyl cyanide p trifluoromethoxyphenylhydrazone, and stimulated by inorganic phosphate. Large amounts of Ca2+ were retained by C. fasciculata mitochondria even after addition of thiols and NAD(P)H oxidants such as t-butylhydroperoxide and diamide. In contrast, Ca2+ was not retained in the matrix of Leishmania sp. mitochondria for long periods of time. In addition to the mitochondrial Ca2+ uptake, a vanadate sensitive Ca2(+)-transporting system was also detectable in these trypanosomatids. PMID- 2233897 TI - Recurrent de novo appearance of small linear DNAs in Leishmania major and relationship to extra-chromosomal DNAs in other species. AB - We have detected several new chromosome-sized DNAs in lines derived from the LT252 isolate of Leishmania major. These DNAs appeared de novo in two clonal lines undergoing methotrexate (MTX) selection (clone 7-R50, clone 15-R50), in a stably MTX-resistant population reverting from MTX pressure (R1000-11-P55rev), and spontaneously during routine serial passage of the wild-type LT252 line in vitro (LT252+). No association of these new DNAs with drug resistance was detected. The new chromosomes were present in multiple copies, stably maintained, linear, and hybridized to a telomere-specific probe, and ranged in size from 180 to 220 kb. Southern blot hybridization revealed that all four new DNAs were related, and the family was designated the 715 class of small linear DNAs (SLDs). A 715-class SLD hybridization probe also identified small chromosomes described previously in Leishmania donovani (LD-1, HU-3 minichromosome) and Leishmania braziliensis (LD-1); LD-1 is known to be related to a smaller circular DNA, CD-1. A cloned probe derived from CD-1 (from K. Stuart and C. Tripp) identified two of the four L. major 715 class of SLDs in addition to the LD-1 DNAs of L. donovani and L. braziliensis, however the 715-class SLD probe did not identify CD-1 itself. L. major and L. donovani possess a homologous 1.5 Mb chromosome containing both the CD-1 and 715 sequences within a 40-kb region, whose size remained unaltered following appearance of the SLDs. These data suggest that SLDs and CD-1 may arise from an evolutionarily conserved chromosomal reservoir. PMID- 2233898 TI - Chromosomal rearrangements and point mutations in the DHFR-TS gene of Plasmodium chabaudi under antifolate selection. AB - Selection of the rodent malaria Plasmodium chabaudi with low levels of the antifolate drug pyrimethamine has previously been shown by us to result in duplication of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene by a duplication of chromosome 7 and subsequent rearrangements. We have selected this resultant parasite line with large doses of pyrimethamine and analysed the DHFR-TS gene and chromosomes for any changes. Increased drug pressure has resulted in reappearance of a chromosome with the same structure as chromosome 7 from DS the parent line. Sequencing of the DHFR gene from each of the chromosomes has identified a single point mutation that results in a serine to asparagine change at position 106. This is the equivalent mutation that has been identified as the key residue in the mechanism of resistance to pyrimethamine in Plasmodium falciparum. There is no apparent increase in transcription of the DHFR-TS gene and the large increase in resistance is most likely a result of the mutation in the DHFR gene. PMID- 2233900 TI - Analysis of the sequences flanking the translational start sites of Plasmodium falciparum. AB - The 5' and 3' regions adjacent to the initiation codon in 22 Plasmodium falciparum sequences were examined. A 5' consensus sequence (AAAA/ATG) was found. Although P. falciparum non-translated DNA is A-rich, A occurred significantly more frequently in the 4 positions preceding the initiation ATG than in adjacent non-translated DNA, suggesting that this consensus sequence has functional significance in the initiation of translation. This region has similarities with the equivalent sequences in yeast and Drosophila but differs markedly from that in vertebrates. No significant bias in nucleotide frequencies was found 3' to the initiation codon. PMID- 2233899 TI - Kinetoplast DNA minicircles are inherited from both parents in genetic hybrids of Trypanosoma brucei. AB - We have examined the inheritance of kinetoplast DNA (kDNA) in gentic crosses of trypanosomes. In 2 independent crosses of Trypanosoma brucei spp. trypanosomes, the kDNA maxicircles which carry the genes for mitochondrial biogenesis, were inherited from one parent only, as already found by other workers. However, the other component of kDNA, the minicircles, were inherited from both parents. This was demonstrated by Southern analysis using cloned minicircle probes. The inheritance of kDNA is therefore not uniparental. Our data point to fusion of the parental kinetoplast DNA networks during genetic exchange, with gradual loss of one or other parental maxicircle type due to random segregation of maxicircles at subsequent mitotic divisions. We infer that the first event of genetic exchange is fusion of parental trypanosomes (either haploid or diploid), followed at some point by fusion of the parental mitochondria. PMID- 2233902 TI - Cerebral glucose metabolism in adults with hyperactivity of childhood onset. AB - BACKGROUND AND METHODS: The cause of childhood hyperactivity (attention deficit hyperactivity disorder) is unknown. We investigated the hypothesis that cerebral glucose metabolism might differ between normal adults (controls) and adults with histories of hyperactivity in childhood who continued to have symptoms. Each patient was also the biologic parent of a hyperactive child. None of the adults had ever been treated with stimulant medication. To measure cerebral glucose metabolism, we administered 148 to 185 MBq (4 to 5 mCi) of [18F]fluoro-2-deoxy-D glucose intravenously to 50 normal adults and 25 hyperactive adults while they performed an auditory-attention task. Images were obtained for 30 minutes with a Scanditronix positron-emission tomograph with a resolution of 5 to 6 mm. Whole brain and regional rates of glucose metabolism were measured with computer assistance by two trained research assistants, working independently, who were blinded to the subjects' status (control or hyperactive). RESULTS: Global cerebral glucose metabolism was 8.1 percent lower in the adults with hyperactivity than in the normal controls (mean +/- SD, 9.05 +/- 1.20 mg per minute per 100 g vs. 9.85 +/- 1.68 mg per minute per 100 g; P = 0.034). In the adults with hyperactivity, glucose metabolism was significantly reduced, as compared with the values for the controls, in 30 of 60 specific regions of the brain (P less than 0.05). Among the regions of the brain with the greatest reductions in glucose metabolism were the premotor cortex and the superior prefrontal cortex. When the seven women with hyperactivity or the six patients with learning disabilities were omitted from the analysis, the results were similar. CONCLUSIONS: Glucose metabolism, both global and regional, was reduced in adults who had been hyperactive since childhood. The largest reductions were in the premotor cortex and the superior prefrontal cortex--areas earlier shown to be involved in the control of attention and motor activity. PMID- 2233901 TI - Mutant dihydrofolate reductase-thymidylate synthase genes in pyrimethamine resistant Plasmodium falciparum with polymorphic chromosome duplications. AB - We have identified dihydrofolate reductase (DHFR) gene point mutations and chromosomal changes in pyrimethamine-resistant mutants selected in vitro of Plasmodium falciparum strain FCR3. A pyrimethamine-resistant derivative of the pyrimethamine-sensitive strain FCR3, FCR3-D8, that had been grown in the absence of pyrimethamine for an extended time, was grown in two concentrations of pyrimethamine, and surviving drug-resistant parasites were subcloned. One selected mutant, FCR3-D81, that grew at 1 X 10(-6) M pyrimethamine, contained a single point mutation in the DHFR domain which caused an amino acid change (Phe to Ser) at amino acid 223, whereas another mutant, FCR3-D85, that grew at 5 X 10( 6) M pyrimethamine had that same mutation and an additional point mutation that changed amino acid 54 (Asp to Asn). The selection of FCR3-D85, whose nucleotide sequence was identical to that previously reported for FCR3-D8, confirmed that the original FCR3-D8 parasite population had changed during extended growth in vitro in the absence of drug pressure. FCR3-D81 and FCR3-D85 cells contained different pairs of polymorphic chromosomes that hybridized to a DHFR-TS probe as well as to three other chromosome 4 specific DNAs, indicating that at least part of chromosome 4 had been duplicated and that these parasites were aneuploid with 15 rather than 14 chromosomes. The mutant DHFR-TS genes were diploid. We consider the roles of the polymorphic chromosome duplications and DHFR point mutation(s) as causes of pyrimethamine resistance. PMID- 2233903 TI - The little women of Loja--growth hormone-receptor deficiency in an inbred population of southern Ecuador. AB - BACKGROUND AND METHODS: Laron-type dwarfism, which is characterized by the clinical appearance of isolated growth hormone deficiency with elevated serum levels of growth hormone and decreased serum levels of insulin-like growth factor I (IGF-I), has been described in approximately 50 patients. This condition is caused by a deficiency of the cellular receptor for growth hormone, and it is transmitted as an autosomal recessive trait, as indicated by an equal sex distribution and a high rate of consanguinity in affected families. We studied 20 patients (19 females and 1 male, 2 to 49 years of age), from an inbred Spanish population in southern Ecuador, who had the clinical features of Laron-type dwarfism. RESULTS: Seventeen patients were members of two large pedigrees. Among the 13 affected sibships, there were 19 affected and 24 unaffected female siblings and 1 affected and 21 unaffected male siblings. The patients' heights ranged from 10.0 to 6.7 SD below the normal mean height for age in the United States. In addition to the previously described features, 15 patients had limited elbow extensibility, all had blue scleras, affected adults had relatively short extremities, and all four affected women over 30 years of age had hip degeneration. Basal serum concentrations of growth hormone were elevated in all affected children (30 to 160 micrograms per liter) and normal to moderately elevated in the adults. The serum level of growth hormone-binding protein ranged from 1 to 30 percent of normal; IGF-I concentrations were low--less than or equal to 7 micrograms per liter in the children and less than or equal to 66 micrograms per liter in the adults (normal for Ecuadorean women, 98 to 238). Serum levels of IGF-II and growth hormone-dependent IGF-binding protein-3 were also low. CONCLUSIONS: We describe an inbred population with a high incidence of growth hormone-receptor deficiency resulting in a clinical picture resembling Laron-type dwarfism but differing principally in showing a marked predominance of affected females. This population, of Mediterranean origin, may be genetically related to other reported populations with Laron-type dwarfism, but with the genetic defect linked to a trait resulting in the early fetal death of most affected males. PMID- 2233904 TI - A randomized, prospective field trial of a conjugate vaccine in the protection of infants and young children against invasive Haemophilus influenzae type b disease. AB - BACKGROUND: Haemophilus influenzae type b is the leading cause of invasive bacterial disease in young children. The capsular polysaccharide vaccine does not protect children at greatest risk (those under the age of 18 months), but a polysaccharide-protein conjugate vaccine has proved to be more immunogenic in this age group. METHODS: We enrolled 114,000 infants in Finland in an open, prospective, randomized trial of a H. influenzae type b capsular polysaccharide diphtheria toxoid conjugate vaccine (polyribosylribitol phosphate-diphtheria toxoid [PRP-D]). Children born on odd-numbered days were vaccinated at the ages of 3, 4, 6, and 14 to 18 months; those born on even-numbered days formed the control group and received the same vaccine at the age of 24 months. RESULTS: After three doses of the vaccine there were 4 cases of verified bacteremic H. influenzae type b disease in the group receiving early vaccination, as compared with 64 cases in the control group, between the ages of approximately 7 and 24 months. The protective efficacy of the vaccine was thus 94 percent (95 percent confidence interval, 83 to 98). No serious adverse effects were reported. The immune response to the conjugate vaccine was characteristic of a T-cell-dependent response when studied in a cohort of 120 infants. The primary immunization series resulted in a geometric mean concentration of anticapsular antibody of 0.53 micrograms per milliliter at the age of seven months, and the fourth dose evoked an anamnestic response, with a mean antibody concentration of 45.22 micrograms per milliliter. CONCLUSIONS: A new conjugate vaccine consisting of the capsular polysaccharide of H. influenzae type b covalently linked to a protein carrier (PRP-D), administered to infants beginning at the age of 3 months, is highly effective in protecting young Finnish children (7 to 24 months old) against invasive H. influenzae type b infections. PMID- 2233905 TI - Impaired antibody response to Haemophilus influenzae type b polysaccharide and low IgG2 and IgG4 concentrations in Apache children. AB - BACKGROUND AND METHODS: Because Native American children are at much higher risk for invasive Haemophilus influenzae type b infection than white children, we compared the antibody responses to H. influenzae type b polysaccharide vaccine in healthy Apache and white children. RESULTS: The concentrations of H. influenzae type b antibody after immunization with polysaccharide vaccine were approximately 10-fold lower in 24-month-old Apache children than in whites of a similar age (P less than 0.01). The decreased response involved H. influenzae type b antibodies of the IgG, IgM, and IgA classes. Concentrations of IgG antibody to tetanus toxoid did not differ significantly, and IgG antibodies to diphtheria toxoid were only twofold lower (P = 0.028). Although total IgG, IgM, and IgA levels were higher in two-year-old Apaches than in whites (all P less than 0.001), IgG2 and IgG4 subclasses were lower (both P less than 0.001). Among the Apaches, individual immunoglobulin levels and allotypes were not significantly correlated with their antibody responses to H. influenzae type b polysaccharide. CONCLUSIONS: Apache children have significant impairment of their antibody response to H. influenzae type b polysaccharide and little or no impairment of their antibody responses to protein toxoids. This immunodeficiency may explain the high incidence of H. influenzae type b infection in this population. PMID- 2233906 TI - Limited efficacy of a Haemophilus influenzae type b conjugate vaccine in Alaska Native infants. The Alaska H. influenzae Vaccine Study Group. AB - BACKGROUND: The prevention of invasive Haemophilus influenzae type b disease requires a vaccine that is effective when administered during the first six months of life. The infants of Alaska Natives are at particularly high risk of invasive H. influenzae type b disease. METHODS: To evaluate the protective efficacy of a H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (polyribosylribitol phosphate-diphtheria toxoid [PRP-D]), we enrolled 2102 Alaska Native infants in a randomized, double-blind, placebo-controlled trial in which either the vaccine or a saline placebo was administered at approximately two, four, and six months of age. RESULTS: After 3969 subject-years of follow-up and 32 episodes of H. influenzae type b disease, the overall incidence of invasive disease was not reduced significantly in the vaccinated subjects (6.0 cases per 1000 patient-years), as compared with the placebo controls (9.6) or with other Alaska Native infants (6.0). After one, two, or three doses there was no significant protective efficacy with the vaccine; after three doses the efficacy was only 35 percent (95 percent confidence interval, -57 to 73). The lack of efficacy was not related to the age at onset of disease, age at immunization, type of disease, degree of Alaska Native heritage, time after immunization, or year of the study. Levels of H. influenzae type b anticapsular antibody in recipients of the vaccine became significantly higher than levels in those who received placebo only after the second and third doses. Even after the third dose, only 48 percent of the vaccinated infants had antibody levels of more than 0.1 microgram per milliliter (geometric mean titer, 0.18). Antibody responses did not vary with the level of maternally acquired antibody, degree of Alaska Native ancestry, or age at time of the first or second immunizations, but they increased with increasing age at time of the third dose (P less than 0.001). CONCLUSIONS: We found no evidence that the PRP-D vaccine provides significant protection, at least for Alaska Native infants, against invasive diseases caused by H. influenzae type b. The ineffectiveness of the vaccine paralleled its limited immunogenicity. PMID- 2233907 TI - Hormonal evaluation of the patient with an incidentally discovered adrenal mass. PMID- 2233908 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 46-1990. A 63-year-old woman with diarrhea and bullous lesions of the buttock. PMID- 2233909 TI - Hyperactivity in childhood. PMID- 2233910 TI - Evaluating the Haemophilus influenzae type b conjugate vaccine PRP-D. PMID- 2233911 TI - Prevention of coronary artery disease. A medical imperative. PMID- 2233912 TI - Transfusion of racially unmatched blood. PMID- 2233913 TI - Prevalence of lymphocytopenia in severe combined immunodeficiency. PMID- 2233915 TI - Another cause of tennis elbow. PMID- 2233914 TI - Acute response to recombinant insulin-like growth factor I in a patient with Mendenhall's syndrome. PMID- 2233916 TI - Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial. AB - BACKGROUND: Preliminary reports suggest that patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia may benefit from the addition of corticosteroid treatment to antibiotic therapy. METHODS: We conducted a double-blind, placebo-controlled trial to assess the efficacy of adjunctive corticosteroids in patients with AIDS and severe P. carinii pneumonia. Patients with marked abnormalities in gas exchange who had been treated with antibiotics for less than 72 hours were randomly assigned to receive either methylprednisolone (40 mg) or placebo every 6 hours for 7 days, in addition to treatment for 21 days with trimethoprim-sulfamethoxazole. The primary outcome measures were survival until hospital discharge and the development of respiratory failure. RESULTS: Twenty-three patients were enrolled in the study; there were no significant differences in base-line clinical or laboratory measures between the two treatment groups. Of 12 patients treated with corticosteroids, 9 (75 percent) survived until hospital discharge, as compared with only 2 of 11 placebo recipients (18 percent) (P less than 0.008). Respiratory failure developed in nine placebo recipients, as compared with only three patients treated with corticosteroids (P less than 0.008). No patient required the interruption or discontinuation of corticosteroid or antibiotic treatment because of toxicity or a complicating event. Because of the marked difference in survival, it was deemed unethical to continue the trial, and the study was terminated. CONCLUSIONS: Early adjunctive corticosteroid therapy can improve survival and decrease the occurrence of respiratory failure in patients with AIDS and severe P. carinii pneumonia. PMID- 2233917 TI - A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group. AB - BACKGROUND: Pneumocystis carinii pneumonia remains a common cause of serious morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). The extensive lung injury that accompanies pneumocystis-associated respiratory failure and the reports of clinical benefit from the use of adjunctive corticosteroids provided the rationale for this prospective multicenter trial. METHODS: A total of 333 patients with AIDS and pneumocystis pneumonia received standard treatment and were randomly assigned to receive either corticosteroids (beginning with the equivalent of 40 mg of prednisone twice daily) or no additional therapy. The primary end points in this unblinded trial were the occurrence of respiratory failure (hypoxemia ratio [partial pressure of arterial oxygen divided by fraction of inspired oxygen] less than 75, intubation, or death), death, and dose-limiting toxicity of the initial standard therapy. RESULTS: Of the patients with confirmed or presumed pneumocystis pneumonia (n = 225 and n = 26, respectively), those assigned to treatment with corticosteroids had a lower cumulative risk at 31 days of respiratory failure (0.14 vs. 0.30, P = 0.004) and of death (0.11 vs. 0.23, P = 0.009), as well as a lower risk of death within 84 days (0.16 vs. 0.26, P = 0.026). The frequency of dose-limiting toxicity of the standard therapy was similar in the two treatment groups. Intention-to-treat analyses of the entire cohort confirmed these findings. Clinical benefit could not be demonstrated, however, for patients with mild disease (hypoxemia ratio, greater than 350), equivalent to a partial pressure of oxygen greater than 75 torr on room air. The patients assigned to corticosteroid treatment had an excess of localized herpetic lesions (26 percent vs. 15 percent, P = 0.04) but not of other infections or of neoplasms. CONCLUSIONS: Early adjunctive treatment with corticosteroids reduces the risks of respiratory failure and death in patients with AIDS and moderate-to-severe pneumocystis pneumonia. Because the adverse effects are few, corticosteroids should be included as part of the initial treatment for persons with AIDS who have moderate-to-severe pneumocystis pneumonia. PMID- 2233919 TI - The evaluation and treatment of seizures. PMID- 2233918 TI - Altered expression of the retinoblastoma gene product in human sarcomas. AB - BACKGROUND: The retinoblastoma-susceptibility (Rb) gene is a prototype tumor suppressor gene originally isolated from patients with heritable retinoblastoma. This gene encodes a nuclear phosphoprotein whose expression is altered in several types of human tumors. METHODS: We studied the expression of the Rb protein in 44 primary and 12 metastatic high-grade human sarcomas by means of immunohistochemical methods and Western blotting. Computerized image analysis was used to quantify the level of Rb gene product in individual tumor cells. The expression of the Rb gene was then correlated with clinical outcome in the patients with primary tumors. RESULTS: Of the 44 patients with primary sarcomas, 13 (30 percent) had tumors with normal, homogeneous expression of the Rb protein in essentially all tumor cells. Thirty-one patients with primary tumors (70 percent) had altered Rb expression; in 18 (40 percent) the Rb protein was heterogeneously expressed, and in 13 (30 percent) it was detected in fewer than 20 percent of the tumor cells. All 12 of the patients with metastatic sarcomas had altered expression of the Rb protein. When the findings in the patients with primary tumors were correlated with clinical outcome, survival was found to be significantly increased in the patients whose tumors had homogeneous Rb expression, as compared with those with either heterogeneous expression (P = 0.026) or no expression (P = 0.012). CONCLUSIONS: Tumors in which the expression of Rb gene product was decreased were more aggressive than tumors in which this protein was expressed by nearly all cells. The Rb gene product may be an important prognostic variable in patients with these tumors. PMID- 2233920 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 47-1990. A 51-year-old man with hemoptysis and cavitary lesions of the left lung. PMID- 2233921 TI - An error corrected, a conclusion withdrawn, and a lesson learned. PMID- 2233922 TI - Conjunctive antithrombotic and thrombolytic therapy for coronary-artery occlusion. PMID- 2233923 TI - Plasma endothelin-1 levels in patients with pregnancy-induced hypertension. PMID- 2233924 TI - Ticlopidine and thrombocytopenia. PMID- 2233925 TI - Prevalence and predictors of rhabdomyolysis in patients with hypokalemia. PMID- 2233926 TI - Improved molecular-genetic diagnosis of Leber's hereditary optic neuropathy. PMID- 2233928 TI - Health insurers and medical directives. PMID- 2233927 TI - The role of Veterans Affairs hospitals in the health care system. PMID- 2233929 TI - Immigrants, international travelers, and HIV. PMID- 2233930 TI - Organ transplantation in HIV-positive patients. PMID- 2233931 TI - The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. AB - BACKGROUND: Nonrheumatic atrial fibrillation increases the risk of stroke, presumably from atrial thromboemboli. There is uncertainty about the efficacy and risks of long-term warfarin therapy to prevent stroke. METHODS: We conducted an unblinded, randomized, controlled trial of long-term, low-dose warfarin therapy (target prothrombin-time ratio, 1.2 to 1.5) in patients with nonrheumatic atrial fibrillation. The control group was not given warfarin but could choose to take aspirin. RESULTS: A total of 420 patients entered the trial (212 in the warfarin group and 208 in the control group) and were followed for an average of 2.2 years. Prothrombin times in the warfarin group were in the target range 83 percent of the time. Only 10 percent of the patients assigned to receive warfarin discontinued the drug permanently. There were 2 strokes in the warfarin group (incidence, 0.41 percent per year) as compared with 13 strokes in the control group (incidence, 2.98 percent per year), for a reduction of 86 percent in the risk of stroke (warfarin:control incidence ratio = 0.14; 95 percent confidence interval, 0.04 to 0.49; P = 0.0022). There were 37 deaths altogether. The death rate was markedly lower in the warfarin group than in the control group: 2.25 percent as compared with 5.97 percent per year, for an incidence ratio of 0.38 (95 percent confidence interval, 0.17 to 0.82; P = 0.005). There was one fatal hemorrhage in each group. The frequency of bleeding events that led to hospitalization or transfusion was essentially the same in both groups. The warfarin group had a higher rate of minor hemorrhage than the control group (38 vs. 21 patients). CONCLUSIONS: Long-term low-dose warfarin therapy is highly effective in preventing stroke in patients with non-rheumatic atrial fibrillation, and can be quite safe with careful monitoring. PMID- 2233933 TI - Prevalence of the human immunodeficiency virus among university students. AB - BACKGROUND AND METHODS: To estimate the magnitude of the human immunodeficiency virus (HIV) epidemic among university students, we conducted a blinded HIV seroprevalence survey at 19 universities throughout the United States. HIV antibody testing was performed on blood collected for routine medical purposes at the student health centers of the participating institutions. At each campus, from 250 to 1000 blood specimens were collected consecutively and tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot analysis. Nonidentifying demographic data were linked with the test results. RESULTS: Of 16,863 specimens in the sample, 30 (0.2 percent) were positive for antibodies to HIV. Positive specimens were found at 9 of the 19 schools. All were from students over 18 years old; 19 (63 percent) were from students over 24. All but 2 of the 30 infected students were men. The seroprevalence rate for men was 0.5 percent (95 percent confidence interval, 0.3 to 0.7), and for women it was 0.02 percent (95 percent confidence interval, 0.002 to 0.066). Seroprevalence increased with age--from 0.08 percent (95 percent confidence interval, 0.04 to 0.15) for students 18 to 24 years old to 1.0 percent (95 percent confidence interval, 0.2 to 2.9) for those 40 or older. CONCLUSIONS: HIV infection is present on U.S. university campuses, although the rate appears to be far lower than that of populations known to be at high risk. The potential clearly exists, however, for the further spread of HIV infection in this population, and preventive measures are needed. PMID- 2233932 TI - The relation between genotype and phenotype in cystic fibrosis--analysis of the most common mutation (delta F508). AB - BACKGROUND AND METHODS: Both the clinical manifestations of cystic fibrosis and the genotypes of patients are heterogeneous, but the associations between the two are not known. We therefore studied blood samples from 293 patients with cystic fibrosis for the presence of the most common disease-causing mutation (delta F508) on chromosome 7 and compared the results with the clinical manifestations of the disease. RESULTS: The prevalence of the delta F508 allele in the cohort was 71 percent; 52 percent of the patients were homozygous for the mutation, 40 percent were heterozygous, and 8 percent had other, undefined mutations. The patients who were homozygous for the mutation had received a diagnosis of cystic fibrosis at an earlier age and had a greater frequency of pancreatic insufficiency; pancreatic insufficiency was present in 99 percent of the homozygous patients, but in 72 percent of the heterozygous patients and only 36 percent of the patients with other genotypes. The patients with pancreatic insufficiency in all three genotype groups had similar clinical characteristics, reflected by an early age at diagnosis, similar sweat chloride values at diagnosis, similar severity of pulmonary disease, and similar percentiles for weight. In contrast, the patients in the heterozygous-genotype and other-genotype groups who did not have pancreatic insufficiency were older and had milder disease. They had lower sweat chloride values at diagnosis, normal nutritional status, and better pulmonary function after adjustment for age. CONCLUSIONS: The variable clinical course in patients with cystic fibrosis can be attributed at least in part to specific genotypes at the locus of the cystic fibrosis gene. PMID- 2233934 TI - Cardiac localization of eosinophil-granule major basic protein in acute necrotizing myocarditis. PMID- 2233935 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 48-1990. A 65-year-old man with pulmonary infiltrates after treatment for Wegener's granulomatosis. PMID- 2233936 TI - Atrial fibrillation--risk marker for stroke. PMID- 2233937 TI - Red-cell cytoskeletal abnormalities--implications for malaria. PMID- 2233938 TI - Heart disease and the eosinophil. PMID- 2233939 TI - Effects of human growth hormone in men over 60 years old. PMID- 2233940 TI - Differences in the quality of semen in outdoor workers during summer and winter. PMID- 2233942 TI - Evaluation of acute aortic dissection by intravascular ultrasonography. PMID- 2233941 TI - Pharmacokinetics of mercaptopurine in children with acute lymphocytic leukemia. PMID- 2233943 TI - New editorial policy on conflicts of interest. PMID- 2233944 TI - When doctors question kids. PMID- 2233945 TI - The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens. AB - BACKGROUND: Bacillary angiomatosis is an infectious disease causing proliferation of small blood vessels in the skin and visceral organs of patients with human immunodeficiency virus infection and other immunocompromised hosts. The agent is often visualized in tissue sections of lesions with Warthin-Starry staining, but the bacillus has not been successfully cultured or identified. This bacillus may also cause cat scratch disease. METHODS: In attempting to identify this organism, we used the polymerase chain reaction. We used oligonucleotide primers complementary to the 16S ribosomal RNA genes of eubacteria to amplify 16S ribosomal gene fragments directly from tissue samples of bacillary angiomatosis. The DNA sequence of these fragments was determined and analyzed for phylogenetic relatedness to other known organisms. Normal tissues were studied in parallel. RESULTS: Tissue from three unrelated patients with bacillary angiomatosis yielded a unique 16S gene sequence. A sequence obtained from a fourth patient with bacillary angiomatosis differed from the sequence found in the other three patients at only 4 of 241 base positions. No related 16S gene fragment was detected in the normal tissues. These 16S sequences associated with bacillary angiomatosis belong to a previously uncharacterized microorganism, most closely related to Rochalimaea quintana. CONCLUSIONS: The cause of bacillary angiomatosis is a previously uncharacterized rickettsia-like organism, closely related to R. quintana. This method for the identification of an uncultured pathogen may be applicable to other infectious diseases of unknown cause. PMID- 2233946 TI - Clinical and pathological features of bacillary peliosis hepatis in association with human immunodeficiency virus infection. AB - BACKGROUND: Peliosis hepatis is characterized by cystic, blood-filled spaces in the liver and is seen in patients with chronic infections or advanced cancer and as a consequence of therapy with anabolic steroids. Cutaneous bacillary angiomatosis is a bacterial infection that occurs in patients with human immunodeficiency virus (HIV) infection; its histologic appearance is that of a pseudoneoplastic vascular proliferation. METHODS: We studied liver tissue from eight HIV-infected patients with peliosis hepatis, two of whom also had cutaneous bacillary angiomatosis. For comparison we examined tissue from four patients who had peliosis hepatis without HIV infection. Tissues were examined histologically on routine sections and with special stains and electron microscopy. RESULTS: The histologic features seen in peliosis hepatis associated with HIV infection, but not in the four cases unrelated to HIV infection, were myxoid stroma and clumps of a granular purple material that on Warthin-Starry staining and electron microscopy proved to be bacilli. The bacilli, which could not be cultured, were morphologically identical to those found in the skin lesions of cutaneous bacillary angiomatosis. The clinical courses of two of the patients with this "bacillary peliosis hepatis" indicate that it responds to antibiotic treatment. CONCLUSIONS: HIV-associated bacillary peliosis hepatis is an unusual, treatable opportunistic infection, probably caused by the same organism that causes cutaneous bacillary angiomatosis. Our failure to find bacilli in non-HIV associated cases implies that other pathogenetic mechanisms may also be responsible for peliosis hepatis. PMID- 2233948 TI - Regional myocardial metabolism of high-energy phosphates during isometric exercise in patients with coronary artery disease. AB - BACKGROUND: The maintenance of cellular levels of high-energy phosphates is required for myocardial function and preservation. In animals, severe myocardial ischemia is characterized by the rapid loss of phosphocreatine and a decrease in the ratio of phosphocreatine to ATP. METHODS: To determine whether ischemic metabolic changes are detectable in humans, we recorded spatially localized phosphorus-31 nuclear-magnetic-resonance (31P NMR) spectra from the anterior myocardium before, during, and after isometric hand-grip exercise. RESULTS: The mean (+/- SD) ratio of phosphocreatine to ATP in the left ventricular wall when subjects were at rest was 1.72 +/- 0.15 in normal subjects (n = 11) and 1.59 +/- 0.31 in patients with nonischemic heart disease (n = 9), and the ratio did not change during hand-grip exercise in either group. However, in patients with coronary heart disease and ischemia due to severe stenosis (greater than or equal to 70 percent) of the left anterior descending or left main coronary arteries (n = 16), the ratio decreased from 1.45 +/- 0.31 at rest to 0.91 +/- 0.24 during exercise (P less than 0.001) and recovered to 1.27 +/- 0.38 two minutes after exercise. Only three patients with coronary heart disease had clinical symptoms of ischemia during exercise. Repeat exercise testing in five patients after revascularization yielded values of 1.60 +/- 0.20 at rest and 1.62 +/- 0.18 during exercise (P not significant), as compared with 1.51 +/- 0.19 at rest and 1.02 +/- 0.26 during exercise before revascularization (P less than 0.02). CONCLUSIONS: The decrease in the ratio of phosphocreatine to ATP during hand-grip exercise in patients with myocardial ischemia reflects a transient imbalance between oxygen supply and demand in myocardium with compromised blood flow. Exercise testing with 31P NMR is a useful method of assessing the effect of ischemia on myocardial metabolism of high-energy phosphates and of monitoring the response to treatment. PMID- 2233947 TI - A newly recognized fastidious gram-negative pathogen as a cause of fever and bacteremia. AB - BACKGROUND: We identified a motile, curved, gram-negative bacillus as the cause of persistent fever and bacteremia in two patients with symptomatic human immunodeficiency virus infection. The same organism was subsequently recovered from a bone marrow-transplant recipient with septicemia and from two immunocompetent persons with week-long febrile illnesses. All the patients recovered after antimicrobial therapy. METHODS AND RESULTS: Primary cultures of blood processed by centrifugation after blood-cell lysis yielded adherent, white, iridescent, morphologically heterogeneous colonies in 5 to 15 days. Subcultures grew in four days on chocolate, charcoal-yeast extract, or blood agar. The organisms stained weakly with safranin and were not acid-fast. Fluorescent antibody tests for legionella and francisella were negative. Biochemical reactivity was minimal and difficult to ascertain. Agar-dilution testing revealed in vitro susceptibility to most antimicrobial agents tested. The cellular fatty acid composition of the isolates was similar, resembling that of Rochalimaea quintana or brucella species, but not Helicobacter pylori or species of campylobacter or legionella. As resolved by gel electrophoresis, cell-membrane preparations of all isolates contained similar proteins, with patterns that differed from that of R. quintana. Patterns of digestion of DNA from all isolates by EcoRV restriction endonuclease were virtually identical and also differed from that of R. quintana. On immunodiffusion, serum from one convalescent patient produced a line of identity with sonicates of all five isolates. CONCLUSIONS: This pathogen may have been unidentified until now because of its slow growth, broad susceptibility to antimicrobial agents, and possible requirement of blood cell lysis for recovery in culture. It should be sought as a cause of unexplained fever, especially in persons with defective cell-mediated immunity. PMID- 2233949 TI - Frequency and costs of diagnostic imaging in office practice--a comparison of self-referring and radiologist-referring physicians. AB - BACKGROUND: To assess possible differences in physicians' practices with respect to diagnostic imaging, we compared the frequency and costs of imaging examinations as performed by primary physicians who used imaging equipment in their offices (self-referring) and as ordered by physicians who always referred patients to radiologists (radiologist-referring). METHODS: Using a large, private insurance-claims data base, we analyzed 65,517 episodes of outpatient care by 6419 physicians for acute upper respiratory symptoms, pregnancy, low back pain, or (in men) difficulty urinating. The respective imaging procedures studied were chest radiography, obstetrical ultrasonography, radiography of the lumbar spine, and excretory urography, cystography, or ultrasonography. RESULTS: For all four clinical presentations, the self-referring physicians obtained imaging examinations 4.0 to 4.5 times more often than the radiologist-referring physicians (P less than 0.0001 for all four). For chest radiography, obstetrical ultrasonography, and lumbar spine radiography, the self-referring physicians charged significantly more than the radiologists for imaging examinations of similar complexity (P less than 0.0001 for all three). The combination of more frequent imaging and higher charges resulted in mean imaging charges per episode of care that were 4.4 to 7.5 times higher for the self-referring physicians (P less than 0.0001). These results were confirmed in a separate analysis that controlled for the specialty of the physician. CONCLUSIONS: Physicians who do not refer their patients to radiologists for medical imaging use imaging examinations more frequently than do physicians who refer their patients to radiologists, and the charges are usually higher when the imaging is done by the self-referring physician. From our results it is not possible to determine which group of physicians uses imaging more appropriately. PMID- 2233950 TI - Blunt trauma during pregnancy. PMID- 2233952 TI - New opportunistic infections--more opportunities. PMID- 2233951 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 49-1990. A 47-year-old Cape Verdean man with pericardial disease. PMID- 2233953 TI - Immunotherapy for allergy to insect stings. PMID- 2233955 TI - High-impact aerobic exercises and vertigo--a possible cause of bilateral vestibulopathy. PMID- 2233954 TI - Protecting severely abused and neglected children. An unkept promise. PMID- 2233956 TI - Theophylline for erythrocytosis after renal transplantation. PMID- 2233957 TI - Infection with a novel, unidentified mycobacterium. PMID- 2233958 TI - Stereotactic radiation for intracranial arteriovenous malformations. PMID- 2233959 TI - Postgraduate experience--the great sex divide in health sciences. PMID- 2233960 TI - Sudden death caused by inhalation of butane and propane. PMID- 2233962 TI - Seizures and other neurologic sequelae of bacterial meningitis in children. AB - BACKGROUND: Although the mortality rate among children with bacterial meningitis has decreased dramatically in recent decades, some patients are left with neurologic sequelae. It has not been clearly established which features of the acute illness predict the chronic neurologic sequelae, including late seizures or epilepsy. METHODS: We followed 185 infants and children prospectively during and after acute bacterial meningitis. The mean duration of follow-up was 8.9 years (range, 0.1 to 15.5). During the first six years standard neurologic examinations were performed; telephone interviews were conducted thereafter. RESULTS: One month after meningitis, 69 children (37 percent) had neurologic abnormalities. Many of these signs resolved within a year, leaving only 26 children (14 percent) with persistent deficits: 18 (10 percent) had only sensorineural hearing loss, and 8 (4 percent) had multiple neurologic deficits. Thirteen children (7 percent) had one or more late seizures not associated with fever. The presence of persistent neurologic deficits indicative of cerebral injury was the only independent predictor of late afebrile seizures (P less than 0.001). CONCLUSIONS: After bacterial meningitis only children with permanent neurologic deficits are at high risk for epilepsy. Those with normal examinations after the acute illness have an excellent change of escaping serious neurologic sequelae, including epilepsy. PMID- 2233961 TI - Long-term outcome after surgical repair of isolated atrial septal defect. Follow up at 27 to 32 years. AB - BACKGROUND: Atrial septal defects have been surgically correctable for more than 30 years. The long-term survival rates among patients treated in the early era of cardiac surgery are poorly documented, but such data are of critical importance to the future medical care, employability, and insurability of these patients. METHODS: To determine the natural history of surgically corrected atrial septal defects, we studied all 123 patients who underwent repair of an isolated defect (ostium secundum or sinus venosus) at the Mayo Clinic between 1956 and 1960, 27 to 32 years after the procedure. The follow-up status of all patients was determined by written questionnaires and telephone interviews. Hospital records and death certificates were obtained if interim hospitalization or death had occurred. RESULTS: The overall 30-year actuarial survival rate among survivors of the perioperative period was 74 percent, as compared with 85 percent among controls matched for age and sex. The perioperative mortality was 3.3 percent (four deaths). Actuarial 27-year survival rates among patients in the younger two quartiles according to age at operation (less than or equal to 11 years and 12 to 24 years) were no different from rates among controls--97 percent and 93 percent, respectively. In the two older quartiles (25 to 41 years and greater than 41 years), 27-year survival rates were significantly less (P less than 0.001)--84 percent and 40 percent, respectively--than in controls (91 and 59 percent). Independent predictors of long-term survival according to multivariate analysis were age at operation (P less than 0.0001) and systolic pressure in the main pulmonary artery before operation (P less than 0.0027). When repair was performed in older patients, late cardiac failure, stroke, and atrial fibrillation were significantly more frequent. CONCLUSIONS: Among patients with surgically repaired atrial septal defects, those operated on before the age of 25 have an excellent prognosis, but older patients require careful, regular supervision. PMID- 2233963 TI - The sequelae of Haemophilus influenzae meningitis in school-age children. AB - BACKGROUND: Previous data on the consequences of Haemophilus influenzae type b meningitis for school-age children have been inconsistent, and much of the information on risk factors has been inconclusive. The present study was designed to evaluate the sequelae of this disease with a protocol for the comprehensive assessment of neuropsychological function. METHODS: Ninety-seven school-age children (mean age, 9.6 years), each of whom had a school-age sibling, were recruited from a survey of the medical records of 519 children treated for H. influenzae type b meningitis between 1972 and 1984 (at a mean age of 17 months) at the children's hospitals of Toronto, Ottawa, and Montreal. Of the 97 children, 41 had had an acute neurologic complication. Sequelae were assessed by comparing the index children with their nearest siblings on the basis of standardized measures of cognitive, academic, and behavioral status. RESULTS: Only 14 children (14 percent) had persisting neurologic sequelae: sensorineural hearing loss in 11 (unilateral in 6 and bilateral in 5), seizure disorder in 2, and hemiplegia and mental retardation in 1. Although the total sample of index children scored slightly below the siblings in reading ability, the 56 children without acute phase neurologic complications (58 percent) were indistinguishable from their siblings on all measures. The differences between the groups were small even for the 41 pairs in which the index child had had an acute neurologic complication (mean full-scale IQ, 102 for the index children vs. 109 for the siblings). Sequelae were also associated with lower socioeconomic status and a lower ratio of glucose in cerebrospinal fluid to that in blood at the time of the meningitis. Behavioral problems were more prominent in index boys than index girls and in those who were older at the time of testing, but sex and age were not related to cognitive or academic sequelae. CONCLUSIONS: We find a favorable prognosis for the majority of children who are treated for meningitis caused by H. influenzae type b. PMID- 2233964 TI - Random ciliary orientation. A cause of respiratory tract disease. PMID- 2233966 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 50-1990. A 65-year-old man with pharyngitis, upper-airway obstruction, and a rash. PMID- 2233965 TI - Two patients with cystic fibrosis, nonsense mutations in each cystic fibrosis gene, and mild pulmonary disease. PMID- 2233967 TI - Atrial septal defect--lessons from the past, directions for the future. PMID- 2233968 TI - Ciliary dysmorphology and dysfunction--primary or acquired? PMID- 2233969 TI - Defining experimental therapy--a third-party payer's dilemma. PMID- 2233970 TI - Platelet hyperreactivity and prognosis in survivors of myocardial infarction. PMID- 2233971 TI - Case 47-1989--sexual precocity. PMID- 2233972 TI - Transmission of HIV by transfusion of screened blood. PMID- 2233973 TI - Finder's fees for research subjects. PMID- 2233974 TI - Legally required disclosure of conflicts of interest. PMID- 2233975 TI - Coelomomyces psorophorae var tasmaniensis Couch + Laird (1988) (Coelomomycetaeceae: Blastocladiales), a fungal pathogen of the mosquito Aedes australis. I: Structural changes in the outer walls of sporangia during germination. AB - The germination of sporangia in Coelomomyces psorophorae var tasmaniensis (C. p. tas.) is uncoordinated and thus there is a mixture of developmental stages in any given population. Continuous urografin gradients separated out the critical stages of germinating sporangia giving four bands, each band representing a consecutive stage of germination. These stages were investigated for changes in the sporangial wall using Transmission Electron Microscopy (TEM). The sporangia have a typical two-layered wall, an electron dense outer layer which can be divided into three distinct sub-layers D1, D2, and D3 and an inner electron transparent secondary wall. Stage 3 sporangia have an intact D1 layer on their outer wall. In the subsequent stages (4 & 4b) there is a progressive breakdown of this layer. PMID- 2233976 TI - Pityriasis versicolor: unicity or duality? PMID- 2233977 TI - Coelomomyces psorophorae var tasmaniensis Couch + Laird (1988) (Coelomomycetaeceae: Blastocladiales), a fungal pathogen of the mosquito Aedes australis. II: Nuclear changes during meiospore formation. AB - The presence of synaptonemal complexes were checked in dividing chromosomes as evidence for meiotic division in germinating sporangia. Continuous urografin gradients were used to separate out the various phases of germinating sporangia, the nuclei were removed and embedded for ultrastructural studies. Meiotic inhibitors were applied to germinating sporangia to retard meiotic division to highlight the synaptonemal complexes. At an early phase of sporangial differentiation dividing nuclei developed with synaptonemal complexes. Meiotic inhibitors and stimulators may be used to control sporangial germination for an induction of a high meiospore count. This may be of crucial importance in the utilization of Coelomomyces spp. as a biological control agent of mosquito species. PMID- 2233978 TI - Versicolorin A hemiacetal, hydroxydihydrosterigmatocystin, and aflatoxin G2 alpha reductase activity in extracts from Aspergillus parasiticus. AB - Versicolorin A hemiacetal was converted to versicolorin C in cell-free systems from Aspergillus parasiticus. The rate of reaction catalyzed by the 35-70% ammonium sulfate fraction was 0.43 nmol min-1 mg-1 with NADPH as cosubstrate and 0.17 nmol min-1 mg-1 with NADH at 25 degrees C at pH 7.4. The product from incubation of 17-hydroxy-16,17-dihydrosterigmatocystin with the 35-70% ammonium sulfate fraction and NADPH was a polar compound which was converted to dihydrosterigmatocystin by 0.4 M HCl. The polar compound is proposed to be the 14,17-hydrated open-chain derivative of dihydrosterigmatocystin. Aflatoxin G2 alpha was also reduced in this system to a polar product tentatively identified as the 13,16-hydrated open-chain derivative of AFG2. The reductase activity may be involved in the formation of reduced intermediates and aflatoxins in cultures of A. parasiticus. PMID- 2233979 TI - Pulmonary aspergillosis due to Aspergillus terreus combined with staphylococcal pneumonia and hepatic candidiasis. AB - A female patient with systemic lupus erythematosus (SLE) developed pulmonary aspergillosis with staphylococcal pneumonia and hepatic candidiasis. Aspergillus terreus, which is a rare causative organism of pulmonary aspergillosis, was identified from a pulmonary lesion by culture. The aleurioconidium production, a characteristic of the genus Aspergillus sect. terrei, was demonstrated on short and irregular hyphal features in tissue sections. This report is the first of a combined case of pulmonary aspergillosis due to A. terreus with infections caused by other microorganisms. PMID- 2233981 TI - Fungi associated with dried fish in Sri Lanka. AB - The mycoflora of dried-salted fish from markets in Kandy, Sri Lanka was studied with emphasis on visibly spoiled dried fish. A total of 61 fungal isolates from 25 dried-fish were isolated and identified. The most prevalent fungus was Aspergillus niger. Species of Aspergillus flavus, A. fumigatus, A. glaucus, A. restrictus, Aureobasidium spp. Basipetospora halophila (a genuinely halophilic fungus) Cladosporium herbarum, Gliomastix, spp., Penicillium chalybeum and Penicillium expansum were present. The isolated fungi did not grow in synthetic media containing more than 30% sodium chloride. Aureobasidium spp. and Gliomastix spp. did not grow on dried-fish under laboratory conditions. The protective exoskeleton appeared to prevent fungal growth on dried shrimp. The A. flavus strains isolated were not aflatoxigenic. PMID- 2233980 TI - Ocular rhinosporidiosis in Tamil Nadu, India. AB - A high incidence of ocular rhinosporidiosis in Kanyakumari district of Tamil Nadu, India is reported. Among the four taluks (sub-division for administration), highest occurrence was found in Agastheeswaram taluk (51.2%) followed by Kalkulam (24.4%), Thovalai (22%) and Vilavancode (2.4%). The disease occurred among both sexes equally and preponderance of a particular sex was not observed. The young adolescents were found to be more susceptible. The disease was found in all socio economic strata and among all communities and persons belonging to different religious groups. Most of the patients gave a history of bathing in muddy stagnant pools of water. PMID- 2233982 TI - Initial attachment of Candida albicans cells to buccal epithelial cells. Demonstration of ultrastructure with the rapid-freezing technique. AB - The rapid-freezing technique was applied in association with scanning and transmission electron microscopy to observe the initial attachment (or contact) of Candida albicans cells to exfoliated human buccal epithelial cells. Low temperature scanning electron microscopy provided detailed three-dimensional morphological features of the yeast-epithelial cell association; adhesion of C. albicans cells to host cells was primarily owing to an interaction between fibrillar layer of the yeast cell wall and the membrane interdigitations of the epithelial cells. Such a particular interconnection between the two cells was confirmed by the freeze-substitution fixation for transmission electron microscopy. These results clearly demonstrate the outermost fibrillar cell wall layer of C. albicans responsible for adhesion to host cells. PMID- 2233983 TI - Antimicrobial activity of naphthoquinones from fusaria. AB - Twenty-two naphthoquinone compounds isolated or derived synthetically from culture extracts of Fusarium solani and F. oxysporum were examined for antimicrobial activity. Fifteen exhibited antibiotic activity against Staphylococcus aureus, and 12 were active against Streptococcus pyogenes, but none were active at the highest rate of 128 micrograms/ml against Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Serratia marcescens, or Pseudomonas aeruginosa. Of 8 plant pathogenic bacteria tested against 11 naphthoquinones, Corynebacterium poinsettiae was inhibited by 6 compounds, and Pseudomonas viridiflava was weakly inhibited by one. Only one of a group of 6 fluorescent soil pseudomonads was inhibited by one naphthoquinone. Antifungal activity of 10 compounds against 8 fungal plant pathogens was limited to inhibition of Phytophthora parasitica by one naphthopyran. PMID- 2233985 TI - The effect of mycophenolic acid on the cell cycle of Candida albicans. AB - Mycophenolic acid inhibited the growth of Candida albicans. Cultures exposed to a concentration of 8.4 micrograms ml-1 mycophenolic acid were found to exhibit cell cycle arrest with two or more buds. Nuclear staining revealed that these were nucleate implying a possible defect in cytokinesis. The results are discussed in relation to the possible mode of action of mycophenolic acid. PMID- 2233986 TI - Alterations in the pathogenicity of one Paracoccidioides brasiliensis isolate do not correlative with its in vitro growth. AB - The in vitro subcultivation of some microorganisms for long periods causes measurable loss of their pathogenicity, which can be reverted by reisolation from infected hosts. We compared the pathogenicity and the in vitro growth pattern of one P. brasiliensis isolate (Pb 18) in its yeast phase, using the following samples: 1) The original pathogenic Pb 18 (OP). 2) Pb 18 attenuated by continuous in vitro subcultivation (AT). 3) Pb 18 (AT) reisolated from susceptible B10.A mice (RS). 4) Pb 18 (AT) reisolated from resistant A/SN mice (RR). Pathogenicity was evaluated by anatomopathology and mortality of mice infected i.p. with 5 x 10(6) fungi. Median survival times of mice infected with OP ranged from 74 to 117 days during the first 51 months of subculturing; with more cycles of subculturing the median survival time increased, reaching 250 days at the 64th month. This indicated decreasing virulence of OP during this period of subculturing. Survival of mice infected with RS and RR was respectively 112 and 123 days, which is similar to the behavior of the OP variant. The in vitro growth curve profile of RR showed significantly higher numbers of total and viable yeasts than the other studied variant. These results show that: 1) Pb 18 isolate loses its pathogenicity by continuous subcultivation. This phenomenon is reverted by reisolation from mice, independently from their susceptibility to the fungus; 2) the in vitro growth patterns of Pb 18 do not correlate with alterations in pathogenicity but are influenced by the host's environment. PMID- 2233988 TI - [The characterization of microbial lipases. 1. The determination of lipase activity]. AB - In the selection of an appropriate method for activity determination of lipases existing technical equipment, kind of enzymes, number of samples investigated (e.g. in routine analysis), and expected sensitivity range have to be taken into account. Titrimetric methods and above all copper salt methods with their high detection sensitivity are the most suitable procedures for activity determination of lipases used in laboratories and institutions without equipment for radiochemical analysis. PMID- 2233989 TI - Drugs of abuse: chemistry, pharmacology, immunology, and AIDS. Introduction. PMID- 2233987 TI - Effect of the ingestion of an extract from Bauhinia monandra seeds on rats. AB - Bauhinia monandra is a leguminous plant that would be used in human nutrition, however it shows a high hemagglutinating activity against trypsin-treated erythrocytes of rabbit, 2 ml of a NaCl-solution extract of the seeds was given to a group of rats for 10 days. Intestinal disaccharidase activity was determined. Histopathological and histochemical examinations were also performed. Lectins from Bauhinia monandra seeds did not cause any visible intestinal damage even when they seem to be able to bind to the enterocyte brush border. The low disaccharidase activity in the membrane and enterocyte fractions, which represent the enzyme synthesis level, indicates that lectins could reduce the synthesis of these enzymes rather than inhibit the active sites of the enzymes. This effect could be in turn related with the binding action of lectins, because no effect of the autoclaved extract on the disaccharidase activity was observed. PMID- 2233984 TI - Review of animal mycoses in Australia. AB - This review covers the available literature on the mycoses of animals in Australia since the last review published in 1967. Of the cutaneous infections, dermatophytoses have been recorded in a wide range of animals: cattle, horses, goats, pigs, sheep, cats, dogs, mice, guinea-pigs, rabbits, a lion, kangaroos, a camel, koalas and wallabies. These infections were caused by several species and varieties of the genera, Microsporum and Trichophyton. Eight agents of ringworms have been recorded in the horse. Two subcutaneous mycoses, phaeohyphomycosis and sporotrichosis have been reported. Phaeohyphomycosis is becoming more common but sporotrichosis is rare having been recorded only once in a cat. The following systemic mycoses have been recorded: adiaspiromycosis, aspergillosis, candidiasis, cryptococcosis, dactylariosis, fusariomycosis, histoplasmosis, miscellaneous mycoses, mycotic abortion and related conditions, zygomycosis, pythiosis, protothecosis and green algal infections. Cryptococcosis has affected 11 different animal species. Mycotic abortion is a serious disease in Victoria. Pythiosis of horses has been extensively studied in northern Australia. PMID- 2233990 TI - Drugs of abuse: chemistry, pharmacology, immunology, and AIDS. A technical review. October 31-November 2, 1988, Rockville, MD. Proceedings. PMID- 2233991 TI - Cocaine receptor--design of ligands. PMID- 2233992 TI - Immunomodulatory effects of chronic morphine treatment: pharmacologic and mechanistic studies. PMID- 2233993 TI - Morphine-induced immune modulation: does it predispose to HIV infection? PMID- 2233994 TI - A murine retrovirus model for studies of the role of cofactors and ethanol in AIDS development. PMID- 2233995 TI - Drug abuse and AIDS: causes for the connection. PMID- 2233997 TI - Novel thebainelike morphinandienes and their Diels-Alder adducts. PMID- 2233996 TI - Immune function in heroin addicts and former heroin addicts in treatment: pre- and post-AIDS epidemic. AB - These studies suggest that specific opiate receptors are not involved significantly in modulating NK-cell activity by any direct effect. The role normally played by the endogenous opioids in directly modulating NK-cell cytotoxic activity may be minimal and certainly is not a clinically relevant controlling factor. These findings also suggest that the repeatedly observed lowering of NK-cell activity in untreated heroin addicts is not due to a direct drug effect. It may be due, however, to an indirect drug effect, possibly by way of altering neuroendocrine function, which we and others have shown predictably occurs during cycles of heroin addiction, and which, as discussed above, has been shown to become normalized during steady-dose, long-term, methadone-maintenance treatment. The lowering of NK-cell activity in heroin addicts may also be due primarily to the use of unsterile needles, with exposure to and infection with multiple diseases as well as injection of many foreign substances. Clinical studies of all the important immunological indices will have to be carried out in well-characterized human populations, including normal healthy control subjects, drug abusers, drug addicts, and former drug addicts in defined treatment status, before the actual roles of drugs of abuse or drugs used to treat drug abuse in immune function in humans will be fully understood. PMID- 2233999 TI - Opiate antagonists and anti-HIV agents. PMID- 2233998 TI - Effect of fluorine substitution on the anti-HIV activity of dideoxynucleosides. PMID- 2234000 TI - Recovery from opiate addiction without treatment: a summary. PMID- 2234001 TI - The role of ethnography in substance abuse research and public policy: historical precedent and future prospects. PMID- 2234002 TI - Women and addiction: process, treatment, and outcome. PMID- 2234003 TI - Chicano intravenous drug users. PMID- 2234004 TI - The German Bridge: a street hookers' strip in the Amsterdam Red Light District. PMID- 2234005 TI - Methodological and design issues: techniques for assessing the representatives of snowball samples. PMID- 2234007 TI - Requirements for inductive analysis. PMID- 2234006 TI - Identifying and gaining access to hidden populations. PMID- 2234008 TI - Computer analysis of qualitative data. PMID- 2234009 TI - Ethnographic field stations. AB - Ethnographic field stations are not a substitute for traditional ethnography, because they provide an "unnatural" setting for research interaction and observation to take place. However, they do provide perhaps the optimal setting for qualitative and quantitative methodologies to be undertaken in a single research effort. In this sense, they are critically important for advancing our knowledge about drug abusers and their behaviors. PMID- 2234010 TI - Ethnographic research on hidden populations: penetrating the drug world. PMID- 2234011 TI - Building blocks. PMID- 2234012 TI - Which dressing? PMID- 2234013 TI - A trialist's perspective of conducting research in ICU. PMID- 2234014 TI - The role of cancer nursing societies in cancer programmes. PMID- 2234016 TI - Copying and copyright. PMID- 2234015 TI - The planning of hospitals. Part III: Planning the New Durban Academic Hospital. PMID- 2234017 TI - AIDS scan. PMID- 2234018 TI - Malaria the forgotten disease? PMID- 2234020 TI - AIDS scan. PMID- 2234019 TI - The victims of violence. PMID- 2234021 TI - A strange caesarean section. PMID- 2234023 TI - The menopause. PMID- 2234022 TI - The nursing care of AIDS patients: caring, not curing. AB - In sum, examination of the complex issues surrounding AIDS brings the disease into clearer focus for the individual health care professional. One of the benefits is that AIDS is causing the nursing profession to re-examine its role in health care. Absence of a cure is not tantamount to having nothing more to offer. In fact, care rather than cure, becomes imperative. The highest quality care possible for all patients irrespective of their background, colour, religion, sexual orientation, diagnosis and prognosis, is a priority. Hopefully everyone in health care and society at large will learn valuable lessons from the AIDS experience. In this context, the role of health care professionals should be that of student learning from the patient. PMID- 2234024 TI - Leadership and the professional nurse. PMID- 2234025 TI - Suntanning? Don't take a chance--take care. PMID- 2234026 TI - The critical care nursing issue: an update. PMID- 2234027 TI - Transcultural nursing. PMID- 2234028 TI - [Health services in the Homelands of the East Transvaal]. PMID- 2234029 TI - Cross-cultural perspectives in breast-feeding. PMID- 2234030 TI - Labour pains. PMID- 2234031 TI - Re-examining the nursing process: Part 1. PMID- 2234032 TI - Electrosurgery--Part 3. Uses of electrosurgery. PMID- 2234033 TI - A gift. PMID- 2234034 TI - Day surgery. PMID- 2234035 TI - Shared experience: post-registration theatre courses and common core learning. PMID- 2234036 TI - Respiration monitoring in the recovery unit. PMID- 2234037 TI - Life without swab racks. PMID- 2234038 TI - Ethics--a proper study for the nurse. PMID- 2234039 TI - Some important medical law cases of interest to theatre nurses. PMID- 2234040 TI - Surgical cement friend or foe? PMID- 2234041 TI - Electrosurgery--Part II. The principles of electrosurgery. PMID- 2234042 TI - Science defeats all odds in US budget. PMID- 2234043 TI - AIDS research. NIH digging in. PMID- 2234044 TI - Research quality. David, meet Goliath. PMID- 2234045 TI - Contraception. Equality for the sexes? PMID- 2234046 TI - Human genome. A different approach. PMID- 2234047 TI - Cancer research. Uncharitable actions. PMID- 2234048 TI - Recipe for safer sauces. PMID- 2234049 TI - Overall mortality and cancer mortality around French nuclear sites. AB - Higher than expected mortality from leukaemia has been observed in the population under age 25 living around Sellafield and Dounreay, nuclear reprocessing plants in the United Kingdom. We report the results of a similar study for the population residing around nuclear sites in France. The number of leukaemia deaths was 58, comparable to the 62 in control areas, and slightly less than the 67 expected from national mortality statistics. Twelve deaths due to Hodgkin's disease were observed around nuclear sites; this is about twice the number of Hodgkin's deaths observed in control areas and twice the number expected from national mortality statistics. This observation must, however, be interpreted in light of the fact that several causes of deaths were studied, increasing the play of chance. PMID- 2234050 TI - X-ray analysis of beta B2-crystallin and evolution of oligomeric lens proteins. AB - The beta, gamma-crystallins form a class of homologous proteins in the eye lens. Each gamma-crystallin comprises four topologically equivalent, Greek key motifs; pairs of motifs are organized around a local dyad to give domains and two similar domains are in turn related by a further local dyad. Sequence comparisons and model building predicted that hetero-oligomeric beta-crystallins also had internally quadruplicated subunits, but with extensions at the N and C termini, indicating that beta, gamma-crystallins evolved in two duplication steps from an ancestral protein folded as a Greek key. We report here the X-ray analysis at 2.1 A resolution of beta B2-crystallin homodimer which shows that the connecting peptide is extended and the two domains separated in a way quite unlike gamma crystallin. Domain interactions analogous to those within monomeric gamma crystallin are intermolecular and related by a crystallographic dyad in the beta B2-crystallin dimer. This shows how oligomers can evolve by conserving an interface rather than connectivity. A further interaction between dimers suggests a model for more complex aggregates of beta-crystallin in the lens. PMID- 2234051 TI - Computer modelling at the single-neuron level. PMID- 2234052 TI - Xeroderma pigmentosum. A gene for tumour prevention. PMID- 2234053 TI - Mitosis. The kinetochore in captivity. PMID- 2234054 TI - Human genetics. Bone disease cracks genetics. PMID- 2234056 TI - Differences in hair and fleece loss. PMID- 2234055 TI - Morbillivirus in dolphins. PMID- 2234058 TI - UK Research Councils. Storm over funding policy. PMID- 2234057 TI - Invariant chain distinguishes between the exogenous and endogenous antigen presentation pathways. AB - Class I MHC molecules acquire peptides from endogenously synthesized proteins, whereas class II antigens present peptides derived from extracellular compartment molecules. This dichotomy is due to the fact that the invariant chain associates with class II molecules in the endoplasmic reticulum, preventing binding of endogenous peptides. The mutually exclusive binding of peptide and invariant chain to class II molecules suggests that the invariant chain might play a part in autoimmune disease. PMID- 2234060 TI - Genetic testing. Still over the horizon. PMID- 2234059 TI - Stimulation of the phosphatidylinositol pathway can induce T-cell activation. AB - The T-cell antigen receptor (TCR) regulates two signal transduction pathways: the phosphatidylinositol (PtdIns) and tyrosine kinase pathways. Stimulation of T cells with antigen or anti-TCR monoclonal antibodies induces an increase in inositol phosphates and diacylglycerol, the second messengers responsible for the mobilization of cytoplasmic free calcium and activation of protein kinase C-4. The TCR also activates a tyrosine kinase that is not intrinsic to the TCR. The relationship between these two signal transduction pathways and their contribution to later T-cell responses is unclear. Studies using variants of a murine hybridoma suggested that the PtdIns pathway might not be necessary for or be involved in regulating interleukin-2 (IL-2) production. To address the relationship between later T-cell responses and the early biochemical signals, we investigated the ability of a heterologous receptor with defined signal transduction function to induce T-cell activation. The human muscarinic subtype-1 receptor (HM1), which elicits PtdIns metabolism in neuronal cells through a G protein-coupled mechanism, also functionally activates this pathway when expressed in the T-cell line Jurkat-derived host, J-HM1-2.2 (ref.8). We show here that stimulation of HM1 alone induced IL-2 production and IL-2 receptor alpha chain expression. HM1 does not induce the tyrosine kinase pathway, suggesting that this pathway does not directly influence later T cell-activation responses. Instead, our studies indicate that activation of the PtdIns pathway is probably sufficient to induce later T-cell responses. PMID- 2234061 TI - Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain. AB - Xeroderma pigmentosum (XP) is an autosomal recessive disease, characterized by a high incidence of sunlight-induced skin cancer. Cells from people with this condition are hypersensitive to ultraviolet because of a defect in DNA repair. There are nine genetic complementation groups of XP, groups A-H and a variant. We have cloned the mouse DNA repair gene that complements the defect of group A, the XPAC gene. Here we report molecular cloning of human and mouse XPAC complementary DNAs. Expression of XPAC cDNA confers ultraviolet-resistance on several group A cell lines, but not on lines of other XP groups. Almost all group A lines tested showed abnormality or absence of XPAC messenger RNAs. These results indicate that a defective XPAC gene causes group A XP. The human and mouse XPAC genes are located on chromosome 9q34.1 and chromosome 4C2, respectively. Human XPAC cDNA encodes a protein of 273 amino acids with a zinc-finger motif. PMID- 2234062 TI - Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs. AB - We have cloned and characterized a mitogen-inducible gene isolated from human T cells that predicts a protein of 968 amino acids. The amino-terminal domain has regions homologous to the oncogene rel and to the developmentally important gene dorsal of Drosophila. The carboxy-terminal domain contains repeat structures found in a variety of proteins that are involved in cell-cycle control of yeast and in tissue differentiation in Drosophila and Ceanorhabditis elegans, as well as in the putative human oncogene bcl-3 and in the ankyrin protein. A truncated form of the product of this gene translated in vitro is a DNA-binding protein which interacts specifically with the kappa B binding site found in many inducible genes, including the enhancer in human immunodeficiency virus. This gene is yet another in a growing list of important regulatory molecules whose expression is transcriptionally induced upon cellular activation. PMID- 2234063 TI - Embryo research. Germany turns clock back. PMID- 2234064 TI - EMBO. Fellowships for East. PMID- 2234065 TI - Scientific misconduct. Chained to the bench. PMID- 2234066 TI - TATA-dependent and TATA-independent transcription at the HIS4 gene of yeast. AB - Two systems of transcription factors stimulate expression of the HIS4 gene of Saccharomyces cerevisiae. High-level transcription induced by amino-acid starvation is mediated by Gcn4(ref.1) and basal transcription is mediated jointly by the factors Bas1 and Bas2 (Pho2). We now show that wild-type Gcn4 requires the TATA element for correct messenger RNA start-site selection, but Gcn4 derivatives with deletions in the activation domain activate HIS4 transcription at the correct mRNA start site (I) in the absence of the TATA element. Gcn4 derivatives that activate TATA-independent transcription show low levels of activation. Similarly, we find that low levels of transcription by Bas1/Bas2 are TATA independent, whereas high levels are TATA-dependent. These results show that the HIS4 TATA element is required for mRNA start-site selection only under conditions of high-level transcription. PMID- 2234067 TI - A downstream initiation element required for efficient TATA box binding and in vitro function of TFIID. AB - The gfa gene encodes glial fibrillary acidic protein, an intermediate filament protein expressed in glial cells. In vitro transcription analysis has shown that the human gfa promoter contains two initiation elements that can independently specify the transcription startpoint. One of the elements is a TATA box 25 base pairs (bp) upstream from the transcription startpoint; the other is located between 10 and 50 bp downstream from the transcription initiation site. We have now shown by transfection that both elements are required for efficient transcription in cultured cells. A partially purified natural human TATA box binding factor (TFIID) from HeLa cells gave footprints that extended from upstream of the TATA box through the downstream initiator. Deletion of the downstream initiator inhibited both TFIID binding to the TATA box and transcription in vitro. In contrast to natural human TFIID, clone human and yeast TFIIDs expressed in bacteria gave footprints covering only the TATA box region, although hypersensitive sites were observed in the downstream region. The cloned TFIIDs also showed less dependence than natural human TFIID on the downstream initiator for both TATA box binding and in vitro transcription. These results suggest that natural human TFIID contains an additional component(s) that contribute(s) to stable TFIID binding and effective transcription by interacting with the downstream initiator. PMID- 2234069 TI - Bills pass at last minute. PMID- 2234068 TI - Product review. New mammalian expression vectors. PMID- 2234071 TI - Public health in Italy. PMID- 2234070 TI - Battle over censorship. PMID- 2234072 TI - Gene targeting. How efficient can you get? PMID- 2234073 TI - Vision. Knowing where you're going. PMID- 2234074 TI - Parasites in Drosophila embryos. PMID- 2234075 TI - Role of nerves in hypertension. PMID- 2234076 TI - When are parasites clonal? PMID- 2234077 TI - Requirement for hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins. AB - By analysis of a temperature-sensitive yeast mutant, a heat-shock protein in the matrix of mitochondria, mitochondrial hsp70 (Ssc1p), is found to be involved both in translocation of nuclear-encoded precursor proteins across the mitochondrial membranes and in (re)folding of imported proteins in the matrix. PMID- 2234078 TI - The role of disparity-sensitive cortical neurons in signalling the direction of self-motion. AB - Movement of an observer through the environment generates motion on the retina. This optic flow provides information about the direction of self-motion, but only if it contains differential motion of elements at different depths. If the observer tracks a stationary object while moving in a direction different from his line of sight, the images of objects in the foreground and in the background move in opposite directions. We have found neurons in the cerebral cortex of monkeys that prefer one direction of motion when the disparity of a stimulus corresponds to foreground motion and prefer the opposite direction when the disparity corresponds to background motion. We propose that these neurons contribute a signal about the direction of self-motion. PMID- 2234079 TI - Reduced levels of hsp90 compromise steroid receptor action in vivo. AB - Signalling by steroid hormones is mediated by receptor proteins that bind hormonal ligands and regulate the transcription of specific genes. The heat-shock protein hsp90 seems to associate selectively with unliganded receptors (aporeceptors), but it has not been determined whether this interaction affects receptor function in vivo. To address the role of hsp90, we have taken advantage of the capacity of mammalian steroid receptors to function in yeast. We constructed a strain of Saccharomyces cerevisiae in which hsp90 expression was regulatable and could be reduced more than 20-fold relative to wild type. At low levels of hsp90, aporeceptors seem to be mostly hsp90-free, yet fail to enhance transcription; on hormone addition, the receptors are activated but with markedly reduced efficiency. Thus hsp90 does not inhibit receptor function solely by steric interference; rather, hsp90 seems to facilitate the subsequent response of the aporeceptor to the hormonal signal. This is the first biological evidence that hsp90 acts in the signal transduction pathway for steroid receptors. PMID- 2234080 TI - Limitation of the size of the vulval primordium of Caenorhabditis elegans by lin 15 expression in surrounding hypodermis. AB - In the nematode Caenorhabditis elegans six hypodermal cells, the vulval precursor cells, are each competent to generate vulval cells. Normally only the three nearest precursor cells to the uterine anchor cell generate the vulva (22 nuclei), while the three others fuse with the non-specialized hypodermal syncytium (hyp7) surrounding each precursor cell and covering the body. Without an inductive signal from the anchor cell, all six vulval precursor cells fuse with hyp7 and no vulva is formed. But without activity of the vulval determination gene lin-15(+), all six cells undergo vulval divisions whether the anchor cell is present or not. Using mosaic analysis, we demonstrate here that lin-15(+) expression is necessary in cells other than the vulval precursor cells or the anchor cell, most probably in the hyp7 syncytium. We propose that lin 15(+) is active in hyp7 in order to repress an intrinsic vulval program in the precursor cells. The inductive signal from the anchor cell counteracts this repression for three precursor cells, allowing them to generate vulval cells. Such a two-signal (repressor/derepressor) mechanism may operate in other cases of tissue induction. PMID- 2234081 TI - Gene replacement in parasitic protozoa. AB - Trypanosomatid protozoa frequently cause severe diseases in humans. Many molecules likely to have a role during the infectious cycle have been identified, yet proof of their function is often lacking. We describe studies in Leishmania major of homologous gene targeting, a powerful method for testing gene function in other organisms. Following introduction of a construct containing dihydrofolate reductase-thymidylate synthase (dhfr-ts) flanking sequences fused to neomycin phosphotransferase, 45% of the colonies contained the planned homologous replacement; this frequency rose to nearly 100% in transfections using low amounts of DNA. Integrative transfection in Leishmania thus resembles that of Saccharomyces cerevisiae in giving predominantly homologous events. To facilitate studies of folate metabolism and chemotherapy the sole dhfr-ts copy in a heterozygous deletion line was replaced, yielding lines that were functionally DHFR-TS-. Although most genes are diploid in trypanosomatids, methods exploiting the high frequency of homologous recombination should permit complete replacement of any parasite gene. PMID- 2234082 TI - An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea. AB - Erythromycin A, a clinically important polyketide antibiotic, is produced by the Gram-positive bacterium Saccharopolyspora erythraea. In an arrangement that seems to be generally true of antibiotic biosynthetic genes in Streptomyces and related bacteria like S. erythraea, the ery genes encoding the biosynthetic pathway to erythromycin are clustered around the gene (ermE) that confers self-resistance on S. erythraea. The aglycone core of erythromycin A is derived from one propionyl CoA and six methylmalonyl-CoA units, which are incorporated head-to-tail into the growing polyketide chain, in a process similar to that of fatty-acid biosynthesis, to generate a macrolide intermediate, 6-deoxyerythronolide B. 6 Deoxyerythronolide B is converted into erythromycin A through the action of specific hydroxylases, glycosyltransferases and a methyltransferase. We report here the analysis of about 10 kilobases of DNA from S. erythraea, cloned by chromosome 'walking' outwards from the erythromycin-resistance determinant ermE, and previously shown to be essential for erythromycin biosynthesis. Partial sequencing of this region indicates that it encodes the synthase. Our results confirm this, and reveal a novel organization of the erythromycin-producing polyketide synthase, which provides further insight into the mechanism of chain assembly. PMID- 2234083 TI - Bidirectional incompatibility between conspecific populations of Drosophila simulans. AB - Cytoplasmic incompatibility (CI) describes the phenomenon whereby eggs fertilized by sperm from insects infected with a rickettsial endosymbiont fail to hatch. Unidirectional CI between conspecific populations of insects is a well documented phenomenon. Bidirectional CI has, however, only been described in mosquito populations, and recently between closely related species of parasitic wasps, where it is of interest as both an unusual form of reproductive isolation and as a potential means of insect population suppression. Here we report on the first known example of bidirectional CI between conspecific populations of Drosophila simulans. Further, we show that defects as early as the first cleavage division are associated with CI. This observation suggests that the cellular basis of CI involves disruption of processes before or during zygote formation and that CI arises from defects in the structure and/or function of the sperm during fertilization. PMID- 2234084 TI - French research. Pleas made for science spy. PMID- 2234086 TI - Bush veto fuels orphan drug act uncertainties. PMID- 2234085 TI - Belt-tightening at MRC. PMID- 2234087 TI - The buck stops with government. PMID- 2234088 TI - Protein conformation. Hinge-bending and folding. PMID- 2234089 TI - Dental caution. PMID- 2234090 TI - Molecular structure of F-actin and location of surface binding sites. AB - Comparisons of three-dimensional maps of vertebrate muscle thin filaments obtained by cryo-electron microscopy and image analysis, reveal the molecular structure of F-actin, the location of the C terminus of the monomer and the positions of the binding sites of tropomyosin, the myosin head and the N-terminal portion of the myosin A1 light chain on the filament. These data provide strong constraints for evaluating models built from the atomic structure of the monomer and the subsequent identification of molecular contacts. PMID- 2234091 TI - New Sivapithecus humeri from Pakistan and the relationship of Sivapithecus and Pongo. AB - New humeri of two species of the Miocene hominoid Sivapithecus are described from near Chinji in Pakistan from between approximately 9 and 11 Myr ago. Sivapithecus, a middle and late Miocene hominoid from Turkey and Indo-Pakistan, is overall unlike any living hominoid, although facial-palatal similarities to the extant orangoutan, Pongo, have been used to support a hypothesis of close relationship. Living hominoids have postcranial similarities assumed to be shared derived, among them features of the proximal humerus. However, the new Sivapithecus proximal humeri differ from those of living hominoids, supporting an alternative hypothesis in which Sivapithecus and Pongo are not closely related. It is not clear how to choose between these incompatible hypotheses. PMID- 2234092 TI - Cellular peptide composition governed by major histocompatibility complex class I molecules. AB - Major histocompatibility complex (MHC) class I molecules present peptides derived from cellular proteins to cytotoxic T lymphocytes (CTLs), which check these peptides for abnormal features. How such peptides arise in the cell is not known. Here we show that the MHC molecules themselves are substantially involved in determining which peptides occur intracellularly: normal mouse spleen cells identical at all genes but MHC class I express different patterns of peptides derived from cellular non-MHC proteins. We suggest several models to explain this influence of MHC class I molecules on cellular peptide composition. PMID- 2234093 TI - Structure, expression and function of a schwannoma-derived growth factor. AB - During the development of the nervous system, cells require growth factors that regulate their division and survival. To identify new growth factors, serum-free growth-conditioned media from many clonal cell lines were screened for the presence of mitogens for central nervous system glial cells. A cell line secreting a potent glial mitogen was established from a tumour (or 'schwannoma') derived from the sheath of the sciatic nerve. The cells of the tumour, named JS1 cells, were adapted to clonal culture and identified as Schwann cells. Schwann cells secrete an autocrine mitogen and human schwannoma extracts have mitogenic activity on glial cells. Until now, neither mitogen has been purified. Here we report the purification and characterization of a mitogenic molecule, designated schwannoma-derived growth factor (SDGF), from the growth-conditioned medium of the JS1 Schwann cell line. SDGF belongs to the epidermal growth factor family, and is an autocrine growth factor as well as a mitogen for astrocytes, Schwann cells and fibroblasts. PMID- 2234094 TI - A mutant T4 lysozyme displays five different crystal conformations. AB - Phage T4 lysozyme consists of two domains between which is formed the active-site cleft of the enzyme. The crystallographically determined thermal displacement parameters for the protein suggested that the amino terminal of the two domains undergoes 'hinge-bending' motion about an axis passing through the waist of the molecule. Such conformational mobility may be important in allowing access of substrates to the active site of the enzyme. We report here a crystallographic study of a mutant T4 lysozyme which demonstrates further the conformational flexibility of the protein. A mutant form of the enzyme with a methionine residue (Met 6) replaced by isoleucine crystallizes with four independent molecules in the crystal lattice. These four molecules have distinctly different conformations. The mutant protein can also crystallize in standard form with a structure very similar to the wild-type protein. Thus the mutant protein can adopt five different crystal conformations. The isoleucine for methionine substitution at the intersection of the two domains of T4 lysozyme apparently enhances the hinge-bending motion presumed to occur in the wild-type protein, without significantly affecting the catalytic activity or thermal stability of the protein. PMID- 2234095 TI - Analysis of the 5-HT receptor in rabbit saphenous vein exemplifies the problems of using exclusion criteria for receptor classification. AB - 5-Hydroxytryptamine (5-HT) contracts ring preparations of rabbit saphenous vein via direct and indirect components, the latter being compatible with a "tyramine like" action at sympathetic nerve terminals. Here an attempt was made to establish the identity of the receptor mediating contraction directly, in terms of the currently accepted proposals (Bradley et al. 1986). Results with agonists suggested 5-HT1-like receptor activation: methylsergide behaved as a partial agonist with microcolar affinity and 5-HT effects were mimicked by 5 carboxamidotryptamine (5-CT) and GR43175. The agonist potency order was 5-CT greater than 5-HT greater than methysergide greater than or equal to GR43175, the same as that reported at the 5-HT1-like receptor in dog saphenous vein (Feniuk et al. 1985; Humphrey et al. 1988). Consistent with this, 5-HT effects were resistant to blockade by the selective 5-HT3 receptor antagonist MDL72222 (1.0 mumol/l). In contrast, methiothepin (0.01-0.3 mumol/l), ketanserin (0.3-30.0 mumol/l) and spiperone (0.3-30.0 mumol/l) each produced surmountable antagonism which, although competitive in nature only for methiothepin (pKB = 9.45 +/- 0.09, 17 d.f.), implied 5-HT2 receptor involvement. The possibility that these discrepancies resulted from mixed populations of 5-HT1-like and 5-HT2 receptors can be excluded because; 1). Ketanserin and spiperone blocked the actions of 5-HT and the selective 5-HT1-like receptor agonist GR43175 with equal facility and 2). Responses to all of the agonists studied were similarly antagonised by flesinoxan (pKB approximately 6.4), a simple competitive antagonist at the receptor in rabbit saphenous vein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234096 TI - Actions of non-peptide ergot alkaloids at 5-HT1-like and 5-HT2 receptors mediating vascular smooth muscle contraction. AB - This report describes the actions of the non-peptide ergot alkaloids methysergide, methylergometrine and ergometrine at two types of 5-HT receptor mediating vascular contraction; the well established 5-HT2 receptor in rabbit aorta and a non-5-HT2 receptor in rabbit saphenous vein which resembles the 5-HT1 like receptor in dog saphenous vein. In the rabbit aorta ergometrine (1 mumol/l) and methylergometrine (0.3 mumol/l), but not methysergide, produced small contractions (14% and 7% respectively of the maximal response to 5-HT). This contraction was not related to activation of 5-HT2 receptors since it was resistant to blockade by ketanserin (0.3 mumol/l). When examined as antagonists of 5-HT-induced contractions of rabbit aorta, each ergot displayed nanomolar affinity at the 5-HT2 receptor but only methysergide behaved as a simple competitive antagonist (pKB = 8.25). Methylergometrine and ergometrine produced surmountable blockade which was accompanied by a non-parallel displacement of the 5-HT concentration-effect curves. The selective 5-HT1-like receptor agonist GR43175 (less than or equal to 30 mumol/l) was devoid of affinity at the 5-HT2 receptor in rabbit aorta. In the rabbit saphenous vein each of the ergots produced concentration-dependent contractions which resulted in overtly biphasic concentration-effect curves. Only the first phase of contraction mimicked the effects of 5-HT and GR43175 since contractions were not blocked by MDL 72222 (1 mumol/l), but were surmountably antagonised by methiothepin (10 nmol/l), ketanserin (0.3 mumol/l) and spiperone (0.3 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234097 TI - The effects of ageing on prejunctional 5-hydroxytryptamine receptors in the rat vas deferens. AB - The prejunctional inhibitory effects of a series of 5-HT1 receptor agonists were examined against the isometric contraction of epididymal portions of rat vas deferens evoked by single stimulus pulses in the presence of nifedipine (10 mumol/l). The 5-HT1A ligand flesinoxan produced inhibition of contractions which was not inhibited by cyanopindolol or yohimbine. However, the prejunctional inhibitory concentration response curve for the 5-HT1 agonist 5 carboxamidotryptamine (5-CT) was biphasic in tissues from 1.5 month old animals but monophasic in tissues from 24 months animals. Cyanopindolol (1 mumol/l) antagonised the inhibitory effects of 5-CT in tissues from 1.5 and 3 month animals but not in tissues from 8 or 24 months animals. Inhibitory actions of 5 CT were not prevented by pretreating animals with pertussis toxin (6 micrograms/kg i.v.), a dose which abolished the negative inotropic response to acetylcholine in rat left atria. It is concluded that the nerve terminals of vas deferens from 1.5 month old animals contain both 5-HT1B and other as yet unclassified 5-HT1 receptors, but that this 5-HT1B-mediated response is lost in maturation and ageing. PMID- 2234098 TI - Muscarinic inhibition of acetylcholine release from a novel in vitro preparation of the guinea-pig trachea. AB - An isolated preparation of the guinea-pig trachea is described which allows the simultaneous measurement of acetylcholine release and smooth muscle contraction. Incubation of the epithelium-free preparation with [3H]choline resulted in the formation of [3H]acetylcholine. Electrical stimulation caused the release of [3H]acetylcholine and a contractile response. Tetrodotoxin and omission of calcium from the medium abolished both the evoked release and contractions. The muscarinic agonists oxotremorine, carbachol and pilocarpine concentration dependently inhibited the electrically evoked acetylcholine release and contracted the tracheal smooth muscle. Pre- and postsynaptic EC50 values for a given agonist were not different. Atropine (100 nmol/l) significantly facilitated the evoked acetylcholine release. A concentration of 10 nmol/l atropine did not change the evoked release but antagonized the inhibitory effect of oxotremorine. It is concluded that presynaptic muscarine autoreceptors inhibit the release of acetylcholine from parasympathetic nerves of the guinea-pig trachea. PMID- 2234099 TI - Pharmacokinetic properties of the antimuscarinic drug [3H]-hexahydro-sila difenidol in the rat. AB - The pharmacokinetics of tritiated hexahydro-sila-difenidol [( 3H]-HHSiD) were examined in rats. Furthermore, the distribution of radioactivity was studied by means of whole body autoradiography. After i.v. administration of 2.9 mg/kg HHSiD plus [3H]-HHSiD to anaesthetized rats bearing a catheter implanted in the ductus choledochus and receiving a mannitol infusion, HHSiD was rapidly distributed and metabolized. Only 5% of the radioactivity was recovered in blood after 23 s and 0.4% after 2.5 h. 64% of the plasma radioactivity could be extracted with hexane from the samples taken 23 s after administration. 52% of the radioactivity was eliminated within 2.5 h, 13% by urinary and 39% by biliary excretion. Following oral administration of 8.6 mg/kg HHSiD plus [3H]-HHSiD there was an absorption of approximately one fourth of the administered radioactivity within 4 h. By means of whole body autoradiography (i.v. injection) as well as by tissue distribution measurement the highest levels of radioactivity were found in bile, urine, lung, kidney, adrenals, liver and pancreas. Thus, after i.v. administration to rats HHSiD is rather quickly distributed, metabolized and excreted. This explains its low antimuscarinic potency in vivo. PMID- 2234100 TI - Differential distribution in, and release from, sympathetic nerve endings of endogenous noradrenaline and recently incorporated catecholamines. AB - Guinea-pig vasa deferentia or hypogastric nerve-vas deferens preparations, preincubated with pargyline (to irreversibly inhibit monoamine oxidase), were exposed to 2.3 mumol/l of unlabelled adrenaline or of 3H-7-(-)-noradrenaline in the presence of hydrocortisone (to inhibit extraneuronal uptake). The vasa deferentia were then mounted in perifusion chambers and subjected to transmural electrical stimulation, electrical stimulation of the nerve, depolarization by potassium (50 mmol/l), or addition of tyramine (40 mumol/l). The evoked overflow of tritium and of unlabelled catecholamines was expressed as a fraction of their tissue content. For all stimuli, the fractional release of the exogenous amines was higher than that of endogenous noradrenaline. Thus, recently incorporated amines are preferentially mobilized irrespective of the particular type of releasing mechanism or the chemical nature of the amine. In vasa deferentia which had been loaded with increasing amounts of adrenaline (by incubating the tissues with adrenaline at concentrations ranging from 0.6 to 160 mumol/l), the fractional release of adrenaline decreased and became closer to that of endogenous noradrenaline. Hence, the access of exogenous catecholamines to the deepest storage sites requires higher concentrations of amines than those needed to reach the more easily releasable pools. Light microscope autoradiographs obtained from slices of vasa deferentia previously loaded with 2.3 mumol/l 3H-(-) noradrenaline showed that the outer layers were strongly labelled with silver grains whereas the inner layers were poorly marked. It is concluded that recently incorporated amines are preferentially stored in varicosities close to the surface of the tissue and, in comparison with endogenous noradrenaline, are preferentially released from sympathetically innervated organs. PMID- 2234102 TI - Central, naloxone-reversible antinociception by diclofenac in the rat. AB - The antinociceptive effect of subcutaneously (s.c.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) administered diclofenac was studied in a series of experiments employing the tail-flick (0.01-10.0 mg/kg body weight i.p., 1-50 micrograms i.c.v., 1-10 micrograms i.t.) and hot-plate (0.01-50 mg/kg body weight i.p., 1-50 micrograms i.c.v., 1-10 micrograms i.t.) models representing somatosensory stimuli and the writhing test (0.001 mg-10 mg s.c., 0.1-200 micrograms i.c.v., 0.1-100 micrograms i.t.) and colorectal distension (1-200 micrograms i.c.v.) models representing noxious visceral stimuli. Diclofenac did not exert any antinociceptive effects in the tail-flick or hot-plate models. In the writhing test, diclofenac dose-dependently inhibited the number of writhings after s.c. administration (0.001-10.0 mg/kg body weight) with an ED50 of 1 mg/kg. A similar dose-dependent action of diclofenac was seen after i.c.v. (0.1-200 micrograms) and i.t. (0.1-100 micrograms) administration with an ED50 of 3 micrograms in both cases. The antinociceptive effect of diclofenac administered s.c., i.c.v. or i.t. was almost completely reversed by pretreatment with naloxone, (1 mg/kg body weight s.c.). In the colorectal distension model, the i.c.v. administration of diclofenac (1-200 micrograms), which attenuated the cardiovascular response to colorectal distension, was reversed by naloxone. The pressor and tachycardia response to a 20 s, 80 mmHg colorectal distension was inhibited by diclofenac 100 micrograms i.c.v. (16.1 +/- 1.7 mmHg or 58% and 39.4 +/- 0.4 bpm or 70% versus control, respectively). It is concluded that diclofenac exerts a central, naloxone-reversible antinociceptive action in experimental animals after noxious visceral stimuli but not after somatosensory stimuli. PMID- 2234101 TI - The heterogeneity of the neuronal distribution of exogenous noradrenaline in the rat vas deferens. AB - After loading of the incubated rat vas deferens with 0.2 mumol/l 3H-noradrenaline (followed by 100 min of wash-out with amine-free solution), the efflux of endogenous and exogenous compounds was determined by HPLC with electrochemical detection and by column chromatography with scintillation counting. Two different types of heterogeneity of labelling were found. The first one is due to the preferential labelling of varicosities close to the surface of the tissue, the second one to the preferential labelling of vesicles close to the surface of loaded varicosities. As diffusion distances within the tissue and within varicosities are then longer for endogenous than for exogenous amine and metabolites, the composition of spontaneous efflux of exogenous compounds differed from that for endogenous compounds. Because of preferential neuronal and vesicular re-uptake of endogenous noradrenaline, the percentage contribution by noradrenaline to overall efflux was: endogenous less than exogenous. While 3H DOPEG was the predominant exogenous metabolite, DOPEG and MOPEG equally contributed to the "endogenous" efflux. Desipramine abolished the consequences of the first heterogeneity of labelling, i.e., it increased the efflux more for endogenous than for exogenous noradrenaline; moreover it decreased the efflux of 3H-DOPEG, but increased that of 3H-MOPEG. The reserpine-like compound Ro 4-1284, on the other hand, abolished the consequences of the second type of heterogeneity; it reduced the specific activity of "total efflux" (i.e., of the sum of noradrenaline + DOPEG + MOPEG) to the specific activity of the tissue noradrenaline. The degree of heterogeneity of labelling was reduced after inhibition of monoamine oxidase and also when the tissues were loaded with 2 or 20 mumol/l 3H-noradrenaline. It is proposed that the various "compartments" and "pools" of noradrenaline described in the literature reflect the two heterogeneities described here. PMID- 2234103 TI - A bradykinin antagonist inhibits carrageenan edema in rats. AB - Bradykinin has been implicated in acute inflammatory reactions. Intradermal injection elicits increased vascular permeability and hyperalgesia, and bioassays have suggested increased bradykinin concentration in inflammatory exudates. Poorly specific inhibitors of kallikrein, the enzyme catalyzing formation of bradykinin, inhibit certain acute inflammatory reactions. However, the lack of a specific bradykinin receptor antagonist has made proof of the hypothesis difficult. In this study, we have used the potent, specific bradykinin antagonist DArg[Hyp3DPhe7] bradykinin (NPC 567) as a probe to examine the role of bradykinin in carrageenan-induced edema in the paws of rats. Subplantar injection of carrageenan led to an increase in immunoreactive bradykinin and metabolic product, desArg9bradykinin. NPC 567 inhibited the development of edema in response to carrageenan, to a maximum 65%. Thus, bradykinin appears to be a major mediator of increased vascular permeability in response to carrageenan. PMID- 2234104 TI - Interaction of adenine nucleotides, UTP and suramin in mouse vas deferens: suramin-sensitive and suramin-insensitive components in the contractile effect of ATP. AB - Effects of various nucleotides, nucleosides and noradrenaline on smooth muscle tension were studied in the isolated mouse vas deferens. alpha, beta-Methylene ATP, ATP gamma S, noradrenaline, ATP and UTP elicited contraction, with potency decreasing in that order; there was no contractile response to adenosine or uridine (up to 100 mumol/l). Prolonged incubation with alpha, beta-methylene-ATP (concentration increased stepwise from 0 to 15 mumol/l) selectively reduced contractions induced by ATP and UTP but not those induced by noradrenaline, and there was cross-tachyphylaxis between ATP and UTP. Suramin (10-300 mumol/l) did not alter the response to noradrenaline but shifted the concentration-response curves for alpha, beta-methylene-ATP, ATP gamma S, UTP and lower concentrations of ATP (0.1-1 mumol/l) to the right. The pA2-values of suramin were 5.2 against alpha, beta-methylene-ATP, 4.8 against ATP gamma S, 5.1 against UTP and 5.4 against lower concentrations of ATP. The effects of higher concentrations of ATP were largely resistant to suramin. The results indicate that the mouse vas deferens possesses contraction-mediating smooth muscle P2x-receptors. UTP also acts at this receptor, and there is no evidence for a separate UTP receptor. The selective inhibition of nucleotide- but not noradrenaline-induced contractions by suramin confirms the view that suramin is a selective P2-antagonist. The resistance against suramin of part of the effect of ATP suggests that ATP activates a suramin-insensitive site in addition to the P2x-receptor. PMID- 2234105 TI - Absorption and metabolism of procaine by the rat small intestine. AB - The aim of this study was to obtain information about the absorption of procaine in the rat small intestine (Fisher-Parsons preparation). In the range from 0.25 10 mmol.l-1 procaine in the luminal perfusate, much more of the unchanged drug was absorbed in segments of the ileum than of the duodenum and jejunum. Besides procaine, two metabolites, p-aminobenzoic acid (PABA) and acetylated p aminobenzoic acid (AABA), formed in the intestinal mucosa, appeared in the absorbate. With increasing substrate concentration in the perfusate the PABA in the absorbate increased considerably in all three segments; from 0.75 mmol.l-1 procaine upwards the PABA produced was highest in the jejunum. AABA formed in the mucosa and measured in the absorbate did not increase in the same manner with increasing substrate concentration; in the absorbate of jejunal segments the amount of AABA was significantly higher than in duodenal and ileal segments. Taking into account that in rats the microclimate of the ileum differs considerably from that of the upper part of the small intestine, the marked difference observed in the absorption of procaine between ileal segments on the one side, and duodenal and jejunal segments on the other, can be explained on the basis of the "non-ionic diffusion" theory. PMID- 2234106 TI - Alteration of cytochrome P-450 by prolonged administration of imipramine and/or lithium to rats. AB - The aim of this study was to investigate imipramine-induced alterations of cytochrome P-450 and to determine whether prolonged concomitant administration of imipramine and lithium results in a pharmacokinetic interaction. Male Wistar rats received imipramine (10 mg/kg i.p.) at 12 h intervals or lithium chloride (100 mg/kg in drinking water) or they were treated with the combination of these drugs for 2 weeks. The long term treatment with imipramine produced a very complex alteration of cytochrome P-450: imipramine increased the level of the cytochrome, but it decreased the rate of its own aromatic hydroxylation in position 2. The rate of N-demethylation in the side chain was not changed. Consequently, in the case of both hydroxylation and demethylation, calculated molecular activities were decreased to 48% and 70% respectively. This differential change in activities corresponded well to the observed decrease of absorption in difference spectra (type I) produced in microsomes by imipramine. Carbamazepine-induced type I difference spectra were also decreased by imipramine pretreatment, but to a lesser extent. In contrast, hexobarbital type I binding was increased by imipramine treatment while type II difference spectra produced by metyrapone were not affected. The preliminary SDS-PAGE analysis of cytochrome P-450 isoenzymes of control and imipramine treated rats showed that the investigated antidepressant markedly intensified a protein band at 50.11 kD while bands at 51.28 kD, 56.20 kD and 56.88 kD were less intensive. These results indicate that the alteration of cytochrome P-450 by imipramine treatment is not only of quantitative but also of qualitative character. Lithium alone given to rats affected neither the concentration of cytochrome P-450 in microsomal protein nor the rate of imipramine metabolism in vitro. Lithium given jointly with imipramine reduced imipramine-induced elevation of cytochrome P-450.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234107 TI - Autoradiographic study of the rat vas deferens incubated with 3H-noradrenaline. AB - Rat vasa deferentia were incubated with 0.2 mumol/l 3H-noradrenaline for 60 min and then washed out with amine-free solution for 100 min. Autoradiography then revealed a preferential labelling of the varicosities in the immediate vicinity of the surface of the tissue. However, when tissues were obtained from reserpine- and pargyline-pretreated rats (to block vesicular uptake and monoamine oxidase), 3H-noradrenaline was able to penetrate more deeply into the tissue. These differences are in accordance with the view that the autoradiographs reflect the 3H-noradrenaline concentration gradient (within the extracellular space) generated by the neuronal uptake of the 3H-amine; the concentration gradient is steeper (and the heterogeneity of labelling is more pronounced) in tissues with intact vesicular uptake and monoamine oxidase than in tissues in which these mechanisms had been inhibited. PMID- 2234108 TI - Black stool. Some light on a dark subject. PMID- 2234109 TI - Hemochromatosis discovered through blood donor screening for alanine aminotransferase. PMID- 2234110 TI - A rationale for evaluation of byssinosis. PMID- 2234111 TI - This here and that there. The night I wrote a prescription on a piece of wood. PMID- 2234112 TI - Recreational safety. PMID- 2234113 TI - Trauma care in North Carolina: an update. PMID- 2234114 TI - David Tillerson Smith. PMID- 2234115 TI - On the AHEC airplanes: Response to Dr. Sedwitz's letter (1990;51:246) PMID- 2234116 TI - A followup to the article on maternal-fetal consultative services. PMID- 2234117 TI - A comment on Dr. Tyor's article, "Nancy Slater's Saga". PMID- 2234118 TI - The importance of maintaining water quality in the dialysis unit. A case study. PMID- 2234120 TI - Negative view of dialysis nurses. PMID- 2234119 TI - Bringing the nurse-tech turf war to an end: a priority for both professions. PMID- 2234121 TI - Quality care and cost containment--a practical approach. PMID- 2234122 TI - Dwindling donations make presumed consent a proposal worthy of consideration. PMID- 2234123 TI - Reporting device-related problems and incidences to the FDA. PMID- 2234124 TI - Guilty until proven innocent? PMID- 2234126 TI - The student practicum: 1990. PMID- 2234125 TI - Who's that knocking at my door? PMID- 2234127 TI - Facilitating expert practice in gerontological nursing. AB - Educators and clinical specialists can collaborate to develop experts in gerontological nursing. The authors use Loevinger's theory of ego development and Benner's model to guide their work. Their teaching strategies are designed to increase self-awareness, add conceptual contexts, broden practice perspectives, and promote professional esteem. PMID- 2234128 TI - Strategic planning: collaboration and empowerment. AB - This article describes a strategic planning process for the redesign of patient care delivery based on a systems approach. The process included an assessment of internal hospital strengths and weaknesses matched with external opportunities and threats in the community that the hospital serves. An essential component of the strategic planning process was collaboration. Two types of collaboration emerged, interdisciplinary and intradisciplinary. The outcome of involving all disciplines in the hospital as well as multiple levels and roles within nursing was a comprehensive implementation plan based on the empowerment of the health care provider, health care recipient, and the health care system. PMID- 2234129 TI - Ethical issues. Least restrictive conditions. PMID- 2234130 TI - Enhancing the success of NCLEX-RN retesters. AB - The widely recognized shortage of nurses, together with uncertain trends in nursing school enrollments, poses a dilemma for the health care industry. This dilemma is aggravated by the loss from the work force of graduate nurses who fail the registered nurse licensure examination. Employer institutions fail to reap the benefits of expensive recruiting and orientation, the graduate nurses face a personal and professional crisis, and a shadow is cast over their nursing school. Out of mutual concern, a tertiary care hospital and its affiliated university school of nursing collaborated to develop a model for a clinically based remedial program to increase the likelihood of passing a licensure retest. Developmental aspects and advantages of this model are described. Issues for consideration prior to implementation of such a program are discussed. PMID- 2234131 TI - Managers' ability to perform: individual and collective assessment findings. AB - Changes in role responsibilities, organizational relationships and mix of professional and non-licensed personnel have increased the need for well prepared managers who can be effective in new work environments. Because such individuals are not readily available, identification of potential managers and development of incumbents are crucial. This article describes how four hospitals used the same unique assessment system to identify the strengths and limitations of 116 managers, the implications of their findings, and subsequent interventions. Suggested also are activities with potential for meeting hospitals' future needs for effective managers. PMID- 2234132 TI - The house of collaboration. PMID- 2234133 TI - A career mobility program for skilled nursing facilities. AB - This article reports the results of a 3-year demonstration project in career mobility for nursing personnel in skilled nursing facilities. The goal of the project was to demonstrate the effectiveness of a career mobility program in addressing service delivery challenges such as recruitment, retention, and satisfaction of nursing personnel in skilled nursing facilities. The project was a joint effort between an educational department of a large university and a major long-term care corporation. The project evaluation addressed the effectiveness of this career mobility program in attracting and retaining nursing personnel, the satisfaction of nursing personnel with their jobs, and whether the additional training affected the quality of care. Five pilot and three comparison sites were designated in Southern California. Survey, self-report, and interview data were collected at yearly intervals and at the completion of the project. Descriptive statistics and analysis of variance formed the basis for data analysis and interpretation. Overall, the findings suggested that the career mobility program has the potential to retain staff who benefit from a career development program. The career mobility program was a valuable strategy, but its success was only as good as the management team's authority to support the program and emphasize its goals. PMID- 2234134 TI - Political issues. Opportunities to share and learn. PMID- 2234135 TI - An interview with Gail R. Wilensky. Interview by Carmella A. Bocchino. AB - In this interview, conducted just 4 months after assuming her new position as Administrator of HCFA, Dr. Wilensky discusses her goals for the agency, the emergence of Medicaid as a separate bureau, Medicare reimbursement policies, and nurses' potential as recognized health care providers. PMID- 2234136 TI - Are nurses less satisfied than other workers? AB - Are nurses less satisfied than other workers? In this study comparing job satisfaction of baccalaureate nurses with elementary teachers and accountants, the three groups rated many aspects of their jobs similarly. Nurses were not comparatively or pervasively less satisfied with their jobs than these other professionals except in the areas of salary, chance for administrative participation, and job security. PMID- 2234138 TI - Shopping for quality: the Greater Cleveland Health Quality Choice Project. AB - The Greater Cleveland Health Quality Choice Project, a competitive strategy for reforming the delivery and reimbursement of health care, can be a model for national health care reform. PMID- 2234137 TI - Staffing accommodations to hospital unit admissions. AB - This study of the flow of patients through five general medical units in a 750 bed medical center described the relentless and unpredictable demand for nursing services (with 80% of the admissions coming from the emergency department) and the resulting costs in terms of supplementary staffing and overtime usage. PMID- 2234140 TI - Economic considerations for epidural anesthesia in childbirth. AB - The relationships between epidural anesthesia and selected intrapartum outcomes was examined in 140 first-term pregnancies. Significant relationships were found with four outcomes: increased use of forceps or vacuum extractor, increased length of second stage labor, increased incidence of Cesarean birth, and increased need for oxytocin augmentation. These findings have significant implications for staffing on labor units and costs. PMID- 2234139 TI - Analysis of ambulatory nursing practice. AB - A nursing patient classification system can be used in ambulatory care to facilitate decision making relative to staffing assignments and to begin examining differences in patients' nursing care requirements according to medical diagnosis or other patient characteristics. PMID- 2234141 TI - The roar of the Titans. PMID- 2234142 TI - Technology administration in the hospital. PMID- 2234143 TI - Patient care automation: the future is now. Part 3. The five rules of automation. AB - Five key principles for creating effective operations optimization-based patient care automation have now been established: (a) The old system architectures did not provide operations optimization; (b) primary patient care optimization (nurses and doctors) must be the central focus of any effective system; (c) the system must provide a platform that allows for eliminating both the retrospective and prospective (subterranean) paper records; (d) point-of-care data capture, including at the bedside, must be provided; and (e) integration around the patient is critical to success. Systems that ignore these principles will ultimately be doomed to repeat the problems of the manual system. Adherence to these principles opens a myriad of possibilities and provides a road map for how such a system should function. The next installment in this series of articles will address the ramifications of integration in system design and system use. The positive effects that such system designs can have on the realization of demonstrable benefits from system technology will also be reviewed. PMID- 2234144 TI - Political involvement: a nursing necessity. PMID- 2234145 TI - Managing cultural diversity: turning demographic factors into a competitive advantage. PMID- 2234146 TI - [Psychiatric is not always psychogenic, especially in the general hospital]. PMID- 2234147 TI - [Vitamin D poisoning; real and spurious]. AB - Vitamin D in large doses is a proper therapy in hypoparathyroidism, osteomalacia, vitamin D-resistant rickets and also in chronic renal failure although in those cases the active metabolite of vitamin D is preferred because of the much shorter biologic halflife. Apart from these disorders there are no good reasons for using megadoses of vitamin D. Pseudo-vitamin D intoxication is caused by granulomatous diseases as a so-called inappropriate calcitriol secretion. In cases of vitamin D intoxication the 25-OHD3 content in the serum is much too high, the parathyroid hormone concentration is suppressed and the I,25-(OH)2D3 level is low, whereas in pseudo-vitamin D intoxication the 25-OHD3 content in the serum is normal and the I,25-(OH)2D3 is seriously elevated. Cultured alveolar macrophages of patients with sarcoidosis can produce I,25-(OH)2D3 as can sarcoid lymph node homogenate. I,25-(OH)2D3 proved to promote the fusion of alveolar macrophages to form polykaryons. Local concentrations of I,25-(OH)2D3 may be higher at sites of granulomatous tissue and can act in a paracrine or autocrine fashion to enhance granuloma formation. The action of glucocorticoids and chloroquine in patients with sarcoidosis and hypercalcaemia is presumably an interruption of the described vicious circle. PMID- 2234148 TI - [The older worker: a medical problem or not?]. PMID- 2234149 TI - [Family practitioner's and specialist's role in the care of the patient with epilepsy]. AB - Differences of opinion between GPs and medical specialists about their roles in the care of patients with epilepsy make it difficult to improve this care. To assess the roles of GP and specialist care a random sample of 500 GPs and all clinical neurologists in The Netherlands were sent a questionnaire about their attitude and actual behaviour towards tasks concerning epilepsy. The response was 54%. Non-response analysis did not bring forward statistically significant differences. Both GPs and specialists considered further diagnosis and starting antiepileptic drug regimens tasks for the specialist. The treatment of attacks in the patient's home situation was considered by both groups as a task for the GP. About other tasks opinions were that they ought to be shared or opinions appeared to be divided. According to the authors tasks about which consensus exists as well as tasks about which opinions differ should be considered carefully: on management level by the Epilepsy consultation group of the Dutch Society of General Practitioners and the Dutch Epilepsy Federation, on care level by introducing a patient information card. PMID- 2234151 TI - [The sickness impact profile; results of an evaluation study of the Dutch version]. AB - The U.S. clinimetric instrument, the sickness impact profile (SIP), was validated for The Netherlands. The SIP is a standardized list of 136 statements aimed at measuring changes of conduct in everyday activities due to sickness, and may be used as a measure of outcome in clinical studies. Three necessary stages of a validation study were performed: translation, assignment of weighing factors to the statements and comparison of SIP measurements in a Dutch and an U.S. open population. The findings were that a good Dutch version of the SIP is available, that there is a strong correlation between the weighing factors assigned to the statements of the Dutch and of the U.S. version, and that the SIP scores of open populations of the two countries are in agreement. The findings for the Dutch open population may be used as reference values in other studies. PMID- 2234150 TI - [Extracardial manifestations in constrictive pericarditis]. AB - Constrictive pericarditis is a slowly progressive disabling disease. The diagnosis is easily overlooked because of the striking extracardial signs and symptoms such as abdominal discomfort, general fatigue, cachexia, ascites and oedema. We describe 7 patients with these symptoms in whom the diagnosis was missed during 0.5-17 years. The decisive clue for correct diagnosis appeared to be the raised central venous pressure. This proves the importance of an accurate physical examination. Other findings were: ascites (7/7), hepatomegaly (7/7), oedema (6/7), narrow pulse pressure (less than or equal to 35 mmHg) (5/7), ECG abnormalities (7/7) and pericardial calcifications on the chest X-ray (5/7). In addition we found slightly raised liver enzymes and a protein-losing enteropathy leading to low serum protein levels. These abnormalities are all explained by the alterations in haemodynamics and lymph flow. The only curative therapy is surgical decortication of the heart. PMID- 2234153 TI - [Tracheotomy and intubation]. PMID- 2234152 TI - [Mega-dosages vitamin D: progressive medicine?]. AB - Although the risk of vitamin intoxication is well recognised, massive doses of these preparations continue to be prescribed, especially in the so-called 'alternative' medical sector. We describe a patient with hypervitaminosis D due to administration of megadoses of vitamin D in the absence of an obvious indication. Mode of action and symptoms of vitamin D intoxication are discussed. It is emphasized that vitamin preparations should only be used when strictly indicated and that close clinical and biochemical supervision is necessary. PMID- 2234154 TI - [Medical therapy in patients with chronic coma; a contribution from nursing home medicine]. PMID- 2234155 TI - [Emergency medicine; a very necessary new discipline]. PMID- 2234156 TI - [Diagnosis and treatment of chronic polymorph light dermatoses]. PMID- 2234157 TI - [Organ donation in a general hospital]. PMID- 2234158 TI - [A misunderstood peripheral facial nerve paralysis and yet not Bell's palsy]. PMID- 2234159 TI - [Heredity: science and society; advice from the Public Health Council]. PMID- 2234160 TI - [Long-term anticoagulant treatment following an acute myocardial infarction]. PMID- 2234161 TI - [Heart aneurysm: pathophysiology, complications and treatment]. PMID- 2234162 TI - [The average costs of an admission to the hospital]. AB - The mean cost of the hospital admission has increased considerably in the last 12 years, to an amount of Dfl. 7,415,- in 1988. However, if the greying of the patient population is taken into account (the elderly on average stay long in hospital), together with the devaluation of the guilder, a clear rise of the mean costs per hospitalization is no longer demonstrable. On the contrary, there is firm evidence to support the view that the cost per hospitalization has actually been decreasing since 1982, the last year before the beginning of budgeting. In addition, a very large amount has been saved due to a considerable decrease of the number of admissions. PMID- 2234163 TI - [Revised guidelines for the treatment of patients with severe traumatic brain injury]. AB - The early assessment and acute treatment of patients with severe traumatic brain injury require a well structured and organized policy. This policy should include rapid transport to, and effective first aid in trauma centres especially equipped for this purpose, adequate communication of information between the (para )medical workers successively involved and a multidisciplinary handling of diagnostics and treatment of the various traumatic and posttraumatic conditions. This requires the imposition of unequivocal priorities known to all concerned. In this paper, which was written in cooperation with the different medical disciplines concerned, the main features of the acute treatment of severe head injury, about which a wide agreement was reached, are worked out in 18 theses. The guidelines regard the admission and first aid, the diagnostic procedures and the conservative and surgical treatment of patients with severe head injury. These guidelines can be developed in the different hospitals into detailed blueprints for the treatment, in accordance with the local situation. PMID- 2234164 TI - [The watermelon stomach; linear convolutions of vascular ectasias in the antrum]. AB - The watermelon stomach or 'gastric antral vascular ectasia' is a rare clinical entity. It may cause persistent blood loss. The endoscopic picture is highly characteristic and consists of parallel erythematous folds in the antrum. Histological characteristics are: dilated mucosal capillaries and venules, containing fibrin thrombi, along with fibromuscular hyperplasia in the lamina propria. In case of severe blood loss partial resection of the stomach or laser photocoagulation is often necessary. PMID- 2234165 TI - [When latex disintegrates, or a mechanical pyloric ulcer]. AB - Complications of Celestin oesophageal tube disintegration are discussed with reference to the case of a patient with a tube inserted because of extrinsic stenosis presenting with upper abdominal complaints. PMID- 2234166 TI - [Biceps tendon rupture]. PMID- 2234167 TI - [Abuse of anticholinergic agents]. PMID- 2234168 TI - [Smoking behavior among family physicians, specialists and students in Rotterdam, 1989]. PMID- 2234169 TI - [Liability for professional mistakes--breakthrough of a taboo?]. PMID- 2234170 TI - [Small intestinal perforation as a complication of treatment with loperamide in a Salmonella typhimurium infection]. PMID- 2234171 TI - [Deep frozen, deeply regretted]. PMID- 2234172 TI - [The melanoma problem in The Netherlands]. PMID- 2234173 TI - [Should congenital melanocytic nevi be removed?]. PMID- 2234174 TI - [Revised consensus melanoma of the skin]. AB - A second consensus meeting on cutaneous melanoma was held on June 15, 1990. The present report concisely discusses the recommended policy concerning the diagnosis and treatment of melanoma. The changes in melanoma management in comparison with the first consensus meeting in 1984 are emphasized. PMID- 2234176 TI - [Epidemiology of melanoma of the skin in The Netherlands: a descriptive study]. AB - A study of the mortality rates of cutaneous malignant melanoma over the period 1950-1985 in The Netherlands showed a fourfold increase of mortality. An analysis by birth cohort suggests a cohort effect: age-specific mortality rates increase with successively younger generations. To determine the incidence of malignant melanoma of the skin data were derived from a registration of histological diagnoses of diseases (PALGA). The estimated numbers of new cases of melanoma of the skin were 1270 and 1372 in the years 1986 and 1987 respectively. Data on the trend in incidence are restricted, but indicate an increase. This descriptive study allows no conclusions about the cause of the rise in incidence and mortality rates. PMID- 2234175 TI - [Melanoma of the skin in the national cause-of-death statistics and in the hospital statistics]. AB - In the last 40 years the national mortality from melanoma of the skin, corrected for age, has increased by over 300%. Figures for males are always higher than those for females and this difference tends to grow larger. Since 1960 it has mostly been the mortality in the age groups 30-69 years that increased. The rise in mortality of older persons has been relatively small. Among the patients treated clinically, females are in the majority and increasingly so from year to year. Probability of survival is better for females than for males. Major shifts seem to occur in the localization of the lesion. Lesions are localized relatively less often in the skin of the head. In males, it is the frequency of melanomas of the trunk that is rising, while melanomas of the extremities are markedly increasing in frequency in both males and females. PMID- 2234177 TI - [Adjuvant regional isolation perfusion of the extremities of patients with stage I melanoma thicker than 1.5 mm]. AB - The use of isolated regional perfusion with melphalan as an adjuvant treatment for stage I melanoma of the extremity continues to be controversial. The present retrospective study evaluates the past 25 years' experience by comparing 227 perfused patients from Groningen with 238 matched controls from five hospitals in The Netherlands and Westphalia (West Germany). All patients underwent wide local excision for a primary extremity melanoma of 1.5 mm or greater in thickness. A proportional hazards regression analysis for recurrence of disease and survival identified the significant prognostic factors, of which, besides level of infiltration, ulceration, age and sex, tumour thickness was found to be the most important. Corrected for these factors, it was not possible to demonstrate a statistically significant effect for perfusion in terms of time to limb recurrence (p = 0.61), time to regional lymph node metastasis (p = 0.11), time to distant metastasis (p = 0.73), disease-free interval (p = 0.42), and survival (p = 0.90). No statistically significant differences were seen for adjuvant perfusion in any of the subgroups. PMID- 2234178 TI - [The 'freckle bus' campaign; an unhealthy phenomenon or a sensible experiment?]. AB - In the summer of 1989 a screening campaign for skin cancer was organized in four seaside resorts of The Netherlands using a mobile examination room. On 4 consecutive Saturdays 3069 individuals were examined. A total of 65 individuals with a suspected lesion were found. Histological reports were obtained on 46 suspected lesions and showed: 6 melanomas (all with a thickness less than 1 mm), 2 squamous cell carcinomas, 23 basal cell carcinomas, 5 dysplastic naevi and 10 benign skin lesions. The positive predictive value of the clinical examination appeared to be 83%. Much publicity was given to the campaign by the (inter)national media. The effects of this publicity were measured by a questionnaire sent to the general practitioners (856) and dermatologists (25) in the region, of whom 44% and 84%, respectively, responded. It appeared that during and after the campaign there had been an increase in the number of consultations for skin lesions, and an increase in the diagnoses of malignant lesions. PMID- 2234179 TI - [Malignant melanoma in a primary care pathologico-anatomical laboratory in 1988 and the freckle bus year]. AB - Our laboratory is specialized in pathology and cytology service to general practitioners (GPs). In 1988 we received approx. 1600 skin biopsies from GPs, two were melanomas. In 1989, when some 3200 biopsies were examined, the number of melanomas increased to 15. In that year a screening service was provided in the summer months using a 'freckle bus'. Only one melanoma patient was sent to the GP for further investigation through this screening service. We presume that the concomitant publicity in the mass media was more important for melanoma detection. The characteristics of the 17 melanomas detected by the GPs were in accordance with published epidemiological data. They were, however, very small with a median diameter of 5 mm. More than 70% of the melanomas had a thickness less than 1 mm. The task of the GP in detecting melanomas is discussed. In our study the GPs act in accordance with the proposed guidelines: they only excise lesions with a low suspicion, the margin being at least 1 mm and all biopsies are verified histologically. PMID- 2234180 TI - [Scintigraphy using I 131 iodobenzylguanidine and malignant melanomas]. AB - The successful use of iodine-131-meta-iodobenzylguanidine (I-131-MIBG) scintigraphy for diagnosis of phaeochromocytoma and neuroblastoma stimulated investigation into its diagnostic and therapeutic usefulness in other neural crest tumours. It appears that there is a difference in capacity to absorb I-131 MIBG between the different tumour types. In I-131-MIBG scintigraphy of carcinoids there are more false negative results in comparison with phaeochromocytomas and neuroblastomas. Melanoma, also a neural crest tumor, turned out to be false negative in 100% of the cases reported until 1989. The authors present a case of a malignant melanoma with metastases in liver and stomach, concentrating I-131 MIBG. Biochemical examination demonstrated that this particular tumour was metabolically very active. It is suggested that the I-131-MIBG-positive scintigram of the melanoma may be related to the level of metabolic activity. By biochemical screening in proven cases of malignant melanoma it may be possible to select cases in which I-131-MIBG scintigraphy is worthwhile with a view to therapeutic application of I-131-MIBG. PMID- 2234181 TI - [Mass screening for skin cancer; experiences in Oss]. PMID- 2234182 TI - [Eurothemes. Physicians and patients without borders]. PMID- 2234183 TI - [The treatment of ankle edema in the elderly in family practice; when and how often are diuretics used?]. PMID- 2234184 TI - [The unborn child as patient; advice from the Public Health Council]. PMID- 2234185 TI - [In-vitro fertilization in The Netherlands]. PMID- 2234186 TI - [Invasive diagnosis and treatment of the urinary tract in the fetus]. PMID- 2234187 TI - [Tubes, cuffs and cannulas]. PMID- 2234188 TI - [Hypertension consensus in The Netherlands]. AB - It is known that mild hypertension is a common disorder and there is increasing evidence that it is possible to decrease the incidence of cardiovascular damage by antihypertensive treatment. Stimulated by the controversy on the identification and treatment of patients with mild hypertension, a Dutch hypertension consensus meeting was held on March 16th 1990. Consensus was reached that the decision to treat should be taken on the basis of both the blood pressure level and the individual risk profile, including hypercholesterolaemia, history of smoking, diabetes, or a family history of cardiovascular disease. Subjects at risk should be identified by selective case finding (persons with known additional risk factors) and screening restricted to men aged 55 to 65 years. All patients should be started on non-pharmacological treatment by decreasing sodium intake, and where necessary reducing body weight and alcohol consumption, and stopping smoking. If antihypertensive drugs are to be given, diuretics, beta-blockers, ACE-inhibitors, and (or) calcium antagonists are the drugs of choice. PMID- 2234189 TI - [An unusual hospital infection: Aeromonas hydrophila infection due to the use of leeches]. AB - A patient is described with an infection with Aeromonas hydrophila after the use of medical leeches to improve the circulation of a congested region of surgery. The use of medical leeches and the treatment of a leech-related infection are discussed. PMID- 2234190 TI - [Valproic acid and stupor]. AB - A patient treated with valproic acid and phenytoin for complex partial epilepsy developed a stupor at therapeutic serum levels of the anti-epileptic agents. A few days after discontinuation of valproic acid, complete recovery occurred. The pathogenic mechanism involved is still obscure. PMID- 2234191 TI - [Eurothemes. Eastern Europe AIDS prevention; a lot of 'policy' but few condoms]. PMID- 2234192 TI - [Treatment of unstable wrist fractures using the external fixator]. PMID- 2234193 TI - [The long-term prognosis of hangman's fractures]. PMID- 2234194 TI - [The risks of diazepam in newborn infants]. PMID- 2234195 TI - Brain brachytherapy for malignant gliomas at Creighton University. PMID- 2234196 TI - Leptomeningeal carcinomatosis: CT and MRI appearances. PMID- 2234197 TI - Health managed care. PMID- 2234198 TI - Medicaid update. PMID- 2234199 TI - Some electrochemical characteristics of synthetic analogs of nucleic acid components. I. Derivatives of cytidine and arabinosylcytosine. An attempt to find correlation among some of their properties. AB - The polarographic reduction and parameter tg alpha of a series of natural and synthetic pyrimidine nucleosides, cytidine derivatives, and the cancerostatic agent arabinosylcytosine were studied. Correlations were found between these newly determined characteristics and capacity factor kappa from HPLC analysis, growth inhibition of E. coli B bacteria, deamination of nucleosides by cytidine deaminase, DNA synthesis, and rate of biotransformation and lipophilicity expressed as log P. It was confirmed that the molecule of nucleosides is complex to such an extent that no linear correlation could be revealed among the respective parameters. Linear correlation was found only in smaller, structurally similar groups of derivatives. PMID- 2234200 TI - Tumor inhibition and hematological improvements by dopamine analog 3,4 dihydroxybenzylamine in mice bearing transplantable carcinoma. AB - The cancer chemotherapeutic efficacy of 3,4-dihydroxybenzylamine (DHBA), a dopamine analog with reduced neurotoxic effects, was evaluated in strain A mice bearing transplantable Ehrlich's ascites carcinoma. The analog was administered intraperitoneally on day 1 post-transplantation at dose schedules of 50, 100 and 200 mg/kg/day for 7 consecutive days. The results demonstrated a significant inhibition of tumor growth and prolongation of the survival time of EAC tumor bearing mice following DHBA treatment. Diminished activity of the growth-related respiratory enzyme succinate dehydrogenase along with the stimulated activity of the lysosomal enzyme beta-glucuronidase in the DHBA-treated tumor cells indicated inhibition of tumor growth as well as active lysis of the tumor cells. Tumor inhibition was accompanied by marked improvements in hemoglobin concentration. RBC count and bone marrow cellularity. The results demonstrated that DHBA did not adversely affect hematological profile of the host while it inhibited the growth of Ehrlich's ascites carcinoma. PMID- 2234201 TI - HPLC determination of methotrexate and its metabolite in serum. AB - Determination of methotrexate (MTX) residues in biological samples (serum, cerebrospinal fluid) was worked out using liquid-liquid and solid-phase extractions and high performance liquid chromatography (HPLC) with UV detection. Clinical samples from patients treated by low and high doses of MTX were analyzed using reversed-phase and ion-pair liquid chromatography, and buffer-methanolic mobile phases. Chromatographic conditions were optimized for the simultaneous determination of MTX and its metabolite and the minimal analysis time was recommended. The results were statistically evaluated, elimination curves and chromatograms have been demonstrated. Solid-phase extraction recovery was 93.1 +/ 1.5% and the determination limit for methotrexate in serum samples was 5.10(-7) mol/l and after the preconcentration of samples 5.10(-8) mol/l. PMID- 2234203 TI - Inhibition of proliferation of HeLa cells by cocultivation with early mouse embryos (preliminary report). AB - Eight- to 16-cell zona-free mouse embryos were cocultivated with 5 to 10 HeLa cells in cultivation drops of 0.1 microliter containing D-PBS medium supplemented with 20% fetal bovine serum. The control group included HeLa cells alone cultivated in the same medium under the same culture conditions. The two cultures were evaluated after 72 hours. The control group showed 147 out of 181 cases of proliferation of HeLa cells (81.22%), whereas HeLa cells cocultivated with zona free mouse embryos only proliferated in 2 out of 156 cases (1.28%). Proliferation of HeLa cells was inhibited even though these were not in direct contact with the embryos. The experiments suggest that the secretory activity of early embryos in culture medium inhibits proliferation of transformed cells via a special agent. PMID- 2234202 TI - In vitro activation of tumoricidal properties of rat peritoneal macrophages using lipopolysaccharide. AB - The peritoneal macrophages from normal Lewis rats were characterized by their capacity to phagocytose, by the presence of nonspecific esterase and Fc receptors. In vitro, these macrophages were maintained in culture 7 and/or 21 days, respectively, and for the last 24 h (activation period) were cultured with 0.1-4.0 micrograms/ml of lipopolysaccharide (LPS) and were found tumoricidal against different rat fibrosarcomas, at a ratio of 50:1 (BP6-Tu2, MC-1 and B77). Macrophage-mediated tumor cytolysis was determined using 51Cr-release assay. The sensitivity of used tumors to macrophage-mediated cyto-toxicity was different. In vivo the transfer of the activated macrophages together with the mentioned tumor cells to rats inhibited the growth of tumors. The adoptive transfer of macrophages activated with "activators" might lead to a new kind of immunotherapy of neoplastic diseases. PMID- 2234204 TI - Hairy cell leukemia and other "hairy-cell" lymphoproliferative disorders (LPD HC): the significance of morphologic, histologic and immunologic studies. AB - In this report the clinical, morphologic, histologic and immunologic findings of 41 patients with hairy lymphoid cells in peripheral blood and/or bone marrow are analyzed. In 27 patients the diagnosis of hairy cell leukemia was established. 14 patients had other variants of lymphoproliferative disorders: malignant lymphoma with hairy cells--7, chronic lymphocytic leukemia with hairy cells--5, and T cell lymphoproliferative disorder with hairy cells--2 patients, respectively. Several variants of malignant lymphoma with hairy cells were defined: lymphocytic, centrocytic and lymphoplasmacytic. The importance of combined use of bone marrow biopsy and immunophenotyping for the correct diagnosis of hairy cell leukemia and other "hairy-cell" lymphoproliferative disorders is stressed. The obtained data suggest relationship between characteristic clinical manifestation (isolated splenomegaly), presence of hairy cells and CD11c-antigen expression. PMID- 2234205 TI - Expression of blood group A and B antigens in gastric cancer examined by monoclonal antibodies. AB - Fourty-eight patients with gastric carcinoma were histologically examined and classified according to Lauren as intestinal or diffuse type. Employing monoclonal antibodies, in all samples the expression of blood group A and B antigens was studied using the method of indirect immunoperoxidase reaction. In patients with blood groups A and AB the comparison of expression revealed marked differences between the intestinal and diffuse type carcinomas. In the intestinal type, the expression of the blood group antigens was highly heterogenous, while diffuse type carcinomas displayed a homogenous expression. The obtained differences support Lauren's classification. The staining of supranuclear regions of tumor cells by the monoclonal antibody HE 10 (which reacts with antigenic determinants A and H of type 3 and 4) was found more frequently in intestinal type carcinomas. The possible prognostic significance of these findings is discussed. PMID- 2234206 TI - Sonography in the evaluation of treatment of differentiated thyroid cancer. First results in 158 patients. AB - Sonographic examination of soft tissues of the neck was used to search for recurrent thyroid cancer in 158 patients. Two hundred and thirty-six sonographic findings were evaluated. Specificity of the method, regardless of the type of recurrence, was 0.96, sensitivity 0.66, precision 0.81, predictive value of negative finding 0.72. This compares favorably with the results of examination by palpation (sensitivity 0.32 to 0.52, according to the type of recurrence), or with those of palpation combined with thyroglobulin estimation (sensitivity 0.50 to 0.60). Most important was the possibility of early detection of unpalpable recurrent lesions showing no radioiodine uptake, or relapses with low thyroglobulin production. Systematic evaluation of out-patients using sonography could lower the need for radioiodine scans that are necessarily connected with thyroid hormone therapy withdrawal and that are usually performed in in-patients. PMID- 2234207 TI - Survival and mortality in a randomized study of lung cancer detection. AB - In a randomized prospective study of lung cancer detection in a high-risk population of over 6000 heavy smokers semiannual screening by X-ray and sputum cytology was compared to screening at a 3-year interval. The comparison of Kaplan Meier estimates of survival curves done without and with correcting for lead-time bias disclosed a rather important impact of lead-time bias on survival comparisons. On the contrary, controlling for possible length bias had no obvious effect on the shape of survival curves. The evaluation of mortality from lung cancer, being used as a basic criterion, indicated no traceable benefit from semiannual screening. The higher incidence of lung cancer in the frequently screened group was paralleled by a higher mortality. It is concluded that currently available screening techniques will not solve the problem of lung cancer mortality in smokers. The results underline the importance of primary prevention for lung cancer. PMID- 2234208 TI - Occupational risk factors for cancer of the larynx in Spain. AB - Spain is one of the countries with the highest incidence of laryngeal cancer and, together with France, is the country with the lowest percentage of women with this disease. In order to identify the occupational risk factors associated with laryngeal cancer in this country a case-control study was performed. Cases included 85 patients with epidermoid carcinoma of the larynx diagnosed in "La Paz" Hospital, Madrid, between 1985 and 1987. A sample of 170 patients from the same hospital was used as control. The results of the study revealed that 56.5% of larynx cancer patients had a sedentary occupation working in the service sector. Exposure to insecticides or silica were strongest risk factors for laryngeal cancer. An association between laryngeal cancer and exposure to fumes, chemical products, mineral dust, or wood dust was not found. PMID- 2234209 TI - Risk for development of cancer in three urban areas of India. AB - The probability of developing cancer by using life table approach has been computed for the population of three metropolitan cities of India based on data of population based cancer registries located at Bangalore, Bombay and Madras. It was observed that the risk for development of malignancy of all sites from 20 to 64 years ranged from 4.73% to 5.28% in males, whereas it was 6.76% to 9.18% in females. The increased risk in females was mainly due to the high risk of development of cancer of the uterine cervix and breast. The available morbidity indices such as cumulative incidence rate and cumulative risk do not account for the mortality experiences of population. The present exercise will be useful in evaluating the changes in the disease spectrum as a result of change in the mortality experiences and population structure. PMID- 2234210 TI - Flow cytometry (FCM) analysis of endometrial hyperplasia and carcinoma. AB - In a series of 52 biopsy specimens (31 endometrial carcinomas, 10 atypical endometrial hyperplasias, and 11 cases of normal endometrium), DNA ploidy and S phase cell fraction were estimated in paraffin-embedded material. DNA aneuploidy was detected in 2 of the 10 atypical endometrial hyperplasias and 7 of the 31 endometrial carcinomas. The majority of aneuploidy was found to be connected with the loss of tumor differentiation. No ploidy disturbances were found in normal endometrium. The S-phase cell fraction value of normal endometrium was significantly lower when compared with that of endometrial carcinoma. The broad variation in S-phase cell fraction values of the endometrial carcinomas and atypical endometrial hyperplasias was in contrast with the low variability of S phase cell values of normal endometrium. Very low incidence of aneuploidy in the group of well differentiated endometrial carcinomas (Grade I) enables the suggestion that the presence of aneuploidy predicts a more aggressive disease and that the detection of an aneuploid stemline in atypical endometrial hyperplasia may already indicate the neoplastic transformation. PMID- 2234211 TI - Microphotometric nuclear DNA analysis in cervical dysplasia of the uterine cervix: its relation to the progression to malignancy and regression to normalcy. AB - The present study was attempted to reveal the predictive value of DNA ploidy pattern of uterine cervical dysplasia cases in relation to cervical carcinogenesis. Microphotometric nuclear DNA analysis using Feulgen stain was carried out in 310 cervical smears of 80 dysplasia cases consisting of 53 cases which progressed to malignancy and 27 cases which regressed to inflammation or normalcy during their follow-up periods. Aneuploid DNA pattern was observed in initial as well as follow-up smears in 69.8% of cases of the progressive group, and in 7.4% of cases of the regressive group. This difference is statistically highly significant (chi 2 27.88, p less than 0.001). In the progressive group, an aneuploid DNA value was observed in 40.0% of mild dysplasia, 71.9% of moderate dysplasia and 90.9% of severe dysplasia. In the regressive group, DNA aneuploidy was observed in only 9.1% of moderate dysplasia. This difference is statistically significant. These findings indicate that an aneuploid DNA value is a risk indicator for malignant potential of dysplasia cases. PMID- 2234212 TI - Modulation of glycoconjugate biosynthesis by 5-hexyl-2'-deoxyuridine in highly metastatic Lewis lung carcinoma cells. AB - The mechanism of action of 5-hexyl-2-'deoxyuridine (HUdR), a compound with antitumor activity, has been investigated in the HM cell lines derived from the highly metastatic variant of Lewis lung carcinoma (3LL-HH). It was shown that this pyrimidine analog did not inhibit the biosynthesis of nucleotides but modified the biosynthesis of glycoconjugates. The incorporation of [14C] glucosamine into cytoplasmic glycoconjugates [glycosaminoglycan (GAG), glycolipid (GL), glycoprotein (GP), neutral polysaccharide (NP)] decreased to a similar level. The [14C]-glucosamine derived radioactivity was reduced to about 60-70% of the untreated controls in the presence of 15 micrograms/ml HUdR, which caused no inhibition of cell proliferation. These results might be explained by the reduced conversion of glucosamine into uridine-5'-diphospho-hexosamine. As more reduction was observed in the glucosamine labeling of glycoconjugates in nuclei and extracellular compartment, it may be conceivable that the intracellular transport of certain glycoconjugates (GAG, GP) is also affected by HUdR. In the extracellular compartment the reduced level of GAG labeling was the most apparent change. However, at a higher concentration of HUdR (75 micrograms/ml) there was a higher radioactivity in the combined GL + GP fraction. Using [35S]-labeling, the GAG fractions also showed a decreased radioactivity but only at the concentration of 75 micrograms/ml HUdR. PMID- 2234213 TI - The role of polyamines as a marker of tumor progression and regression in experimental tumors. AB - The pattern of changes in the polyamine spectrum has been studied under the stress of Sarcoma 180, a transplanted tumor growing in the peritoneal cavity of mice. Retinol, a known inhibitor of ornithine decarboxylase, was used to modulate tumor growth pattern and subsequent changes in the level of polyamines. The polyamine levels showed an increase during tumor proliferation. In the treated group, however, the enhanced levels exhibited a tendency to decrease, along with tumor inhibition, indicating that a positive correlation exists between the polyamine content in the red blood cells of mice and the tumor growth pattern. PMID- 2234214 TI - Stimulating effect of blood serums from tumor-bearing rats on cholesteryl ester synthesis in normal rat liver cytosol in vitro. AB - Addition of diluted blood serum from tumor-bearing rats stimulated significantly the synthesis of cholesteryl esters from labeled cholesterol and endogenous fatty acids in the cytosol derived from normal rat liver. With both Zajdela and Walker transplantable tumors this effect was found to be associated with the most intensive period of tumor growth. During chemical carcinogenesis induced by a single subcutaneous administration of benzo(a)pyrene the stimulating effect of sera was found to precede several weeks the appearance of palpable tumors and persisted during the period of progressive tumor growth. With all tumors used, sera in ultimate stages of tumor growth failed to show a stimulating effect. The stimulating effect was due to the presence of a yet unidentified lipid. Higher quantities of this substance may appear in the serum of tumor-bearing animals to meet higher requirements for cholesteryl esters during tumor growth. The stimulating effect of the blood serum on cholesteryl esters may be a useful marker of malignant tumors in humans. PMID- 2234215 TI - Long-term carcinogenicity bioassay of the herbicide atrazine in F344 rats. AB - In Fischer F344/LATI rats of both sexes the herbicide atrazine was given in the diet at concentrations of 0, 375 and 750 ppm for 126 weeks. Food and water consumption was similar in the treated and control groups. Feeding of atrazine resulted in dose-dependent depression of body weight gain in both sexes. There was no difference in the survival among the females. The males in the treated groups lived significantly longer than the controls. Exposure to atrazine resulted in significantly increased incidence of mammary tumors in the high dose male group. Uterine carcinomas were observed at a dose-related, significantly increased incidence. The number of combined leukemias/lymphomas increased in the treated males and females, but it was statistically significant only for females. The total number of malignant tumors showed a dose-related increase in both sexes. Other tumors and nontumorous lesions occurred at background level and were not influenced by treatment. PMID- 2234216 TI - Some electrochemical characteristics of synthetic analogs of nucleic acid components. II. Derivatives of uridine and arabinosyluracil. An attempt to find correlation between some of their properties. AB - The relation between half-wave potentials E1/2, parameter tg alpha, and chemical structure of a series of natural and synthetic compounds of nucleic acids were studied. This series included the pyrimidine nucleobase uracil, the natural pyrimidine nucleoside uridine and its deoxy-derivatives, the synthetic analog arabinosyluracil, its deoxy- and thio-analogs, and some cyclonucleosides. It was confirmed that the value of tg alpha, which may suggest a potential carcinogenic activity of the compounds studied, is dependent upon lipophilicity and rate of biotransformation of these compounds. Generally, it was shown that the complexity of nucleoside molecules makes it impossible to find parameters showing correlation. Linear correlation was found only in small, structurally similar groups of derivatives. PMID- 2234217 TI - Treatment of murine EL4 leukemia in ascitic form with anti-Thy 1.2 specific immunotoxins. AB - C57BL/6 mice with EL4 leukemia cells in ascitic form were intraperitoneally treated with ricin A chain-multivalent antibody immunotoxins. The immunotoxins containing rabbit IgG anti-Thy 1.2 antibodies complemented by protein A of Staphylococcus aureus were able to interact specifically with the target cells and to induce an antitumor effect as revealed by an increase in survival time of the mice. No apparent secondary effects consecutive to a cytotoxic action on the normal Thy 1.2 antigen bearing cells were observed with the immunotoxin doses used. PMID- 2234219 TI - Antitumor activity of Borrelia burgdorferi cultures. AB - Cultures of B. burgdorferi, their supernatants as well as washed cells revealed in vitro a considerable antitumor activity against cells of Gardner lymphoma. Nemeth-Kellner lymphoma and LP-2 plasmacytoma. In in vivo tests an inhibition of tumor growth was evident, even if the treatment was started on day 4 after implantation of the tumor. The best results were obtained with the supernatants of the cultures. PMID- 2234220 TI - Management of patients with brain metastases of unknown origin. AB - During the years 1973-1987, 75 patients were irradiated for brain metastases of unknown origin at the Institute of Oncology in Ljubljana. Of these, 35 (47%) were previously treated by surgery: Metastases were completely removed in 22 patients and partially in 7, whereas biopsy alone was performed in 6 patients. Based on the examinations carried out during radiation therapy and at the time of follow up, the primary sites of tumor were established as follows: The lung in 40 patients, the breast in 2, melanoma in 2, and the esophagus, kidney, and parotid gland in one patient, respectively. Primary tumor could not be detected in 28 (37%) patients. Metastases were microscopically verified in 48 cases in which anaplastic carcinoma and adenocarcinoma were most frequent. All the patients were irradiated on a cobalt unit, generally with doses of 10 x 300 cGy in 2 weeks. Median survival of the 22 patients with total removal of brain metastases was 9.5 months, one-year survival being achieved in 41% of cases. In the remaining patients median survival was 3 months, whereas only 12% of the patients survived one year. The cause of death were most frequently, i.e. in 45 patients, brain metastases. PMID- 2234218 TI - On the background of differences in survival of female breast cancer patients in the German Democratic Republic and the Estonian SSR. AB - The aim of this study was to describe the age-specific survival patterns and to analyse the differences between the survival rates of female breast cancer patients in the German Democratic Republic in 1976-1977 and the Estonian SSR in 1968-1981. The estimated 5-year relative survival rate (RSR) was 64.1% in the GDR and 55.9% in Estonia. Patients aged 55 years or older at diagnosis had higher survival in the GDR (5-year RSR 62.6%) than in Estonia (49.5%). That result was clearly connected with higher proportion of advanced tumors among older patients in Estonia. For patients younger than 55 years the difference of the 5-year RSR between the both countries was not statistically significant (GDR 65.3%, Estonia 63.4%). The standardization of overall 5-year RSR by stage and age, but also only by stage of the disease produced virtually equal results for the GDR and Estonia. It means that the main source of the differences in overall breast cancer survival rates between the GDR and Estonia are the discrepancies in stage distribution, particularly in older age groups. PMID- 2234221 TI - [Recent developments in ultrasound study of cerebral arteries and their clinical value]. PMID- 2234222 TI - [Pattern of cerebral infarct in computerized tomography. Pathophysiologic concepts, validation and clinical relevance]. AB - Our pathogenetically oriented classification system of hemispheric brain infarctions is reviewed. New data are presented to validate this classification from various points of view. A retrospective analysis of 73 patients with large striato-capsular infarcts demonstrated that two-thirds of them had a source of embolism either in the carotid bifurcation or in the heart. SPECT-imaging in patients with hemispheric brain infarctions of various origin revealed that the area of exhausted cerebral perfusion reserve largely exceeds the area of the infarct visible on CT if a hemodynamically caused low-flow infarction is present. This is not the case in the territorial type. Measurement of the hemispheric vasomotor reactivity to capnic stimuli confirmed this finding by demonstrating a severely reduced VMR in low-flow infarctions, but not in thrombo-embolically caused territorial infarctions. Lacunar infarctions due to occlusion of single long penetrating arteries should be judged as either "unequivocal", "probable" or "possible lacunae" and should be differentiated from small lacunar-like infarctions in the cortex ("non-lacunae") which represent small territorial infarctions due to thromboembolism of small pial arteries. Infarctions in the temporo-parieto-occipital watershed area are difficult to distinguish from territorial infarctions within the posterior part of the middle cerebral artery distribution. For research purposes, such patients should be excluded in order to keep the subgroups homogeneous. Consequences of this classification system for diagnostic and therapeutic strategies in stroke patients are discussed. PMID- 2234223 TI - [Cerebral ischemia in young adults. Typical causes and diagnostic problems]. PMID- 2234224 TI - [Diagnosis and prognosis of acute cerebellar infarcts. A retrospective study]. AB - 37 patients with acute cerebellar infarction were analysed retrospectively. Diagnosis of cerebellar infarction cannot be made by clinical symptoms alone rather together with CT and MRT displaying the localisation and size of the lesion. Evoked potentials do predict clinical outcome more accurately than EEG or doppler sonography do. PMID- 2234226 TI - [Measuring premorbid performance capacity]. PMID- 2234225 TI - [Orthostatic dysregulation in Parkinson syndrome. Results of a study of 250 patients]. PMID- 2234227 TI - [Aneurysms of the anterior inferior cerebellar artery. A case report and review of the literature]. AB - A case of an anterior inferior cerebellar artery (AICA) aneurysm in a 63-year-old female who had suffered from subarachnoid hemorrhage and died after repeated bleeding is presented. A review of 26 cases available from literature is given. Clinical symptomatology and diagnostic procedures are discussed. PMID- 2234228 TI - [Traumatic rupture of the inferior petrous sinus with fatal subarachnoid hemorrhage after a fall on the back of the head]. PMID- 2234229 TI - [Familial paroxysmal dystonic choreoathetosis]. PMID- 2234230 TI - [Hemiballism as the primary symptom of AIDS]. PMID- 2234231 TI - Anatomy and physiology of the mechanism of continence. PMID- 2234232 TI - Anal hemorrhoids. PMID- 2234233 TI - Proctitis. AB - An overview is given of the various aspects of idiopathic proctitis. Special emphasis is given on the diagnostic possibilities especially the endoscopic appearances. The list of other inflammatory conditions to be considered in the differential diagnosis is long and includes especially infectious disorders, Crohn's disease, post-radiation abnormalities, caustic damage and ischaemic damage. The mainstay of therapy is topical application of measalazine and corticosteroids. In general measalazine appears to be equally effective as corticosteroids. PMID- 2234234 TI - General perianal skin problems. AB - In this paper attention is focused on the following conditions: perianal skin problems such as pruritus in the perianal area, the eczemas, psoriasis, premalignant and malignant tumours such as Bowen's disease and Bowenoid papulosis, squamous cell carcinoma, dermatophyte and yeast infections and sexually transmitted diseases such as syphilis, condylomata acuminata (warts) and genital herpes. Principles of clinical, bacteriological and histopathological diagnosis will be discussed briefly for each of the above-mentioned diseases. For some of these, therapeutic effectiveness and particular side effects due to the use of topically applied drugs containing corticosteroids, anaesthetics, antibiotics and preservatives will also be considered. PMID- 2234235 TI - Perianal complications in Crohn's disease. PMID- 2234236 TI - Extra-ordinary forms of proctitis. PMID- 2234238 TI - Abstracts of The Netherlands Society of Gastroenterology. 1988 and 1989. PMID- 2234237 TI - Radiology of anorectal diseases. PMID- 2234239 TI - Treatment of renal failure in the primary hyperoxalurias. PMID- 2234241 TI - Radical esophagectomy on a maintenance hemodialysis patient. PMID- 2234240 TI - Aortobronchial fistula complicated with an aortic aneurysm in hemodialysis patient. PMID- 2234242 TI - Cardiac risk score for coronary artery disease and preparation for kidney transplantation. PMID- 2234243 TI - Intraperitoneal cisapride for the treatment of diabetics with gastroparesis and end-stage renal disease. PMID- 2234244 TI - In vitro production of 'glomerular red cells': role of pH and osmolality. AB - We used an in vitro model consisting of a polycarbonate filter with pore diameters of 3 microns, through which red cells suspended in urine or buffer were pumped at a flow rate of 0.5 ml/min. pH and osmolality of the suspension were systematically changed within a range of pH 5-8 and 200-800 mosm/kg H2O. It was found that: (1) glomerular shapes could be produced by this filtration technique; (2) urine facilitated the production of glomerular shapes; (3) certain shapes occurred predominantly, at specific conditions of pH and osmolality and (4) hemolysis decreased with increasing osmolality or very low pH. These observations shed light on the mechanism by which glomerular red cell shapes are formed. PMID- 2234245 TI - Ocular and auditory toxicity in hemodialyzed patients receiving desferrioxamine. AB - During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible. PMID- 2234246 TI - Urinary excretion of apolipoproteins bound to HDL-like particles in rat nephrotic syndrome and their relation to plasma HDL. AB - Lipoprotein excretion was investigated in the urine of hyperlipidemic rats with nephrotic syndrome induced by aminonucleoside of puromycin. Incubation with phosphatidylcholine liposomes was employed to float apoproteins not bound to lipids, by ultracentrifugation at d = 1.21 g/ml. On ultracentrifugation of whole, untreated urine, the amount of protein floated was 6-fold greater in nephrotic vs. control rats and consisted mainly of HDL-like particles. Sodium dodecylsulfate-polyacrylamide gel electrophoresis showed that control urine contained apoproteins A-I, A-II, E and traces of C, whereas in the nephrotic urine apo-E and a large amount of apo-C was found. Addition of liposomes to the ultracentrifugal d = 1.21 g/ml infranate and reflotation at the same density resulted only in slight increment in the floated apoproteins, mainly C and A-I. Addition of liposomes to the whole urine and centrifugation at d = 1.21 g/ml also did not produce a greater yield in the floated apoproteins of control or nephrotic urine. These results indicated that the urine is virtually devoid of lipid-free apoproteins and those floated from both the nephrotic and control urine are complexed with lipids. The plasma VLDL + LDL fraction of nephrotic rats, though increased in quantity, did not differ markedly in composition from that of control rats. The HDL, approximately 3-fold elevated in nephrotic rats, were poorer in esterified cholesterol and richer in phospholipids. Relative to plasma HDL, the nephrotic urine HDL were protein-rich and phospholipid-poor and appeared to be larger in particle size as suggested by the lower estimated specific volume. The modified plasma HDL in nephrosis may have a pathophysiological implication. PMID- 2234247 TI - Serum immunoglobulin levels and natural antibodies to Haemophilus influenzae in hemodialysis patients: evidence for IgG subclass imbalances. AB - Humoral immune parameters were studied in 13 patients with end-stage renal failure on maintenance hemodialysis. Serum IgA, IgM and IgG concentrations were comparable to control values from 14 healthy blood donors. IgG subclass analysis revealed significantly increased IgG1 levels in the patients when compared to controls (p less than 0.01). In 3 patients, IgG2 deficiency was found, in one case associated with low IgG3 level. Concentrations and subclass composition of naturally occurring antibodies to Haemophilus influenzae type b (Hib) polysaccharide (PS) were measured using an indirect ELISA. In patients IgM and IgG, including IgG1 and IgG2 antibodies to Hib, presented no difference from controls. Subclass analysis of Hib specific IgG antibodies revealed that IgG2 accounted for a substantial amount of the anti-Hib PS antibody response in controls as well as in patients. We conclude that patients on maintenance hemodialysis present imbalances of immunoglobulin levels. However, the antibody response to certain PS antigens could remain unaffected by renal failure. PMID- 2234248 TI - Endotoxemia in patients on hemodialysis. AB - We examined endotoxins and limulus amebocyte lysate-reactive material (LAL-RM) in serum from 87 patients on hemodialysis, using the conventional chromogenic limulus test (CCLT) and a new specific endotoxin assay with factor G-free LAL (endotoxin-specific test: EST). All patients with regenerated cellulose dialyzers had increased CCLT values, whereas the EST values were not higher than in controls. This discrepancy can be explained by the LAL-RM which is cellulose derived and cross-reacts with LAL via factor G. Using EST for measurements of endotoxin, 6 patients out of 87 had pathological endotoxemia and all of these patients were associated with either cirrhosis, infection, or malignancy. Some patients who had no complications showed fever before or during dialysis, but they did not have high endotoxin levels. EST is useful for the diagnosis of endotoxemia in patients on hemodialysis because of the presence of LAL-RM in serum. Endotoxemia is rare in patients on hemodialysis, if they are not associated with infection, cirrhosis, or other complications. PMID- 2234249 TI - Urinary IgA, secretory IgA and secretory component in women with recurrent urinary tract infections. AB - Urinary secretory IgA (sIgA), consisting of free secretory component (FSC) and dimeric IgA, is involved in the defense against urinary tract infections (UTI). Recurrent UTIs (rUTI) have been suggested to be associated with a defective excretion of sIgA. Therefore urinary sIgA, FSC and serum-type IgA concentrations were measured by ELISA in 68 normal women, 10 asymptomatic women with rUTIs and no urological abnormality (group A), 8 asymptomatic women with rUTIs and a urological abnormality (B), 4 women with acute UTI (C) and 5 women with a selective serum IgA deficiency (D). Annual UTI rates were increased in groups A, B and C, but normal in group D. In no patient group urinary FSC concentration was different from the normals, while sIgA concentrations were increased in group C, markedly reduced in group D, but normal in groups A and B. Urinary serum-type IgA concentrations were significantly increased in group A and C, markedly reduced in group D and normal in group B. These results demonstrate that the urinary sIgA system participates in the immune response to bacterial infections, but that even a complete failure of the sIgA system does not lead to an increased UTI rate. Furthermore, no association of recurrent UTIs with disturbances of the urinary sIgA excretion could be demonstrated. PMID- 2234250 TI - Sustained-release bezafibrate corrects lipid abnormalities in patients on continuous ambulatory peritoneal dialysis. AB - A study was undertaken in 24 Chinese patients on maintenance continuous ambulatory peritoneal dialysis, using bezafibrate in its sustained-release form to correct lipid abnormalities. Six patients who received 400 mg/day developed severe muscle weakness with grossly elevated creatine phosphokinase activities within 3 weeks. The drug was discontinued and the symptoms disappeared. The remaining 18 patients received 400 mg/week for 8 weeks. There was a significant decrease in serum triglyceride (2.74 +/- 0.33 to 1.86 +/- 0.17 mmol/l at the 4th week and 1.65 +/- 0.4 mmol/l at the 8th week). Concomitantly, serum total cholesterol decreased. Serum high-density lipoprotein cholesterol increased significantly (from 1.18 +/- 0.082 to 1.36 +/- 0.060 mmol/l at the 4th week and 1.40 +/- 0.103 mmol/l at the 8th week). Post-heparin lipoprotein and hepatic lipases were measured by a substrate-specific method. The former increased significantly (p = 0.000) after bezafibrate treatment while the latter did not change. All parameters of lipid metabolism returned towards baseline 4 weeks after discontinuation of therapy. The drug was well tolerated at 400 mg/week and there was no significant rise in serum creatine phosphokinase. PMID- 2234251 TI - Oxyphil cells of parathyroid glands in chronic renal failure may not secrete parathyroid hormone. AB - To evaluate the function of parathyroid oxyphil cell in chronic renal failure, we studied the histopathological findings of 148 parathyroid glands of 42 patients (29 males, 13 females) on maintenance hemodialysis. The individual and total weights of resected parathyroid specimens in each patient were recorded. Using the morphometrical analyzing system, we measured the oxyphil cell area and total area in each excised section taken through the maximum diameter, to estimate them in each patients. According to the fractional ratio (R:oxyphil cell area/total area), patients were divided into four groups: group I (R less than 1%), group II (1% less than or equal to 5%), group III (5% less than or equal to R less than 10%) and group IV (10% less than or equal to R). There were no differences in age, duration of hemodialysis and serum C-PTH level among the different groups. There was a positive correlation not only between total glandular weight and serum C-PTH level, but also between total glandular weight and total area, and also a positive correlation was found between serum C-PTH level and total area. No tendency was found between oxyphil cell area and serum C-PTH level. However, in 15 patients whose oxyphil cell area was more than 10 mm2, there was a negative correlation between the area and serum C-PTH level. Also, in 16 patients whose R was more than 5%, there was a negative correlation between the rate and serum C PTH level. These results suggested that oxyphil cell in chronic renal failure might not secrete PTH. PMID- 2234252 TI - Pattern of double glomerulopathies. A clinicopathologic study in nine nondiabetic patients. AB - Nine new cases of double glomerulopathies (GP) were found among 1,715 renal biopsies. Immunofluorescence and electron microscopy were needed to achieve a correct diagnosis and the prevailing relevance of these techniques in single cases was stressed. IgA nephropathy was the most commonly found GP, being associated with membranous glomerulonephritis (GN) (2 patients), minimal change disease (3 patients), and focal segmental glomerulosclerosis (1 patient). In addition, single cases of membranous GN plus crescentic GN and acute GN plus cryoglobulinemic GN were recorded. Possible factors involved in the pathogenesis and clinical significance of double glomerulopathies are discussed. PMID- 2234253 TI - Elimination of iohexol, a low osmolar nonionic contrast medium, by hemodialysis in patients with chronic renal failure. AB - The dialyzability of iohexol was examined in patients with chronic renal failure on long-term hemodialysis treatment. Eight patients had iohexol (Omnipaque 240 or 350 mg I/ml) injected in doses between 98 and 1,493 mg I/kg body weight (BW) 25 h (mean time) before start of hemodialysis. Dialysance of iohexol was 81 +/- 15 ml/min (mean +/- SD) compared to 120 +/- 16.8 ml/min for creatinine. Elimination half-life for iohexol during hemodialysis was 3.9 +/- 1.1 h while plasma clearance was 64 +/- 17 ml/min. The distribution volume calculated (0.25 +/- 0.05 liters/kg BW) confirms previous observations with distribution in the extracellular fluid only. Before the start of hemodialysis 36 +/- 28% of the dose injected was eliminated, indicating some extrarenal elimination. After 4 h of hemodialysis 72 +/- 11% of the dose was removed. PMID- 2234254 TI - Dynamic pulmonary accumulation of labelled neutrophils by blood membrane contact in the pig. AB - Nine anesthetized pigs were subjected to short (90 min) sham dialysis with blood membrane contact with the aim to select effects of the artificial surface during dialysis. The importance of the neutrophil (PMN) was investigated by the selective isotope labelling, dynamically followed by gamma-camera imaging and biochemical assays specifically oriented for PMN function. These assays included cell count, PMN aggregation, PMN luminescence, fibronectin and catalase activity. Additionally, pulmonary and systemic hemodynamics and acid base balance were monitored. Sham dialysis induced an accumulation of labelled PMN attaining a maximum between 15 and 17 min. This was coupled with a time-related neutropenia, pulmonary vasoconstriction, increased in vitro PMN aggregation and luminescence response. The neutrophil response abated by the end of dialysis. Cardiac output and arterial blood pressure declined to a steady level after 30 min of sham dialysis. There was an insignificant decrease in catalase activity. All other parameters remained unaltered. The results indicate that PMN accumulates in the pulmonary vessels, in association with neutropenia and activation. The transience of the event points to a protective mechanisms of humoral and/or cellular character. PMID- 2234255 TI - Acute renal failure of renovascular origin: cure by aortorenal reconstruction after 25 days of anuria. AB - A case of dialysis-dependent acute renal failure due to bilateral renal artery occlusion is described. Renal function was improved dramatically by revascularization after 25 days of anuria and no further dialysis was required. PMID- 2234256 TI - Uric acid handling, pregnancy and cyclosporin in renal transplant women. PMID- 2234257 TI - [Harvey Cushing: neurosurgeon and artist]. AB - Harvey Cushing was a man of many talents. He was a skilled, surgeon, scientist, author and bibliophile. In addition, he was an accomplished artist for both medical non-medical subjects. In this paper, we present three surgical drawings of Dr Cushing's that are representative of the nearly one hundred drawings we have thus far found with his operative notes in the Peter Bent Brigham Archives. We will also discuss Cushing's non-medical art, some of the best of which is of the French countryside. PMID- 2234258 TI - [The retrolabyrinthine approach. Its value in the treatment of lesions of the lateral sinus]. AB - The Authors conceive the petrous bone as made of four segments bounded by two vertical plans, one passing through the anterior wall of the internal auditory canal and the posterior wall of the external auditory canal, the other passing through the inner aspect of the tympanic cavity and the outer aspect of the labyrinthe. Drilling away one or several segments realizes a trans-petrous approach which always begins by drilling away the posterior-external segment, the retro-labyrinthine segment. Drilling away only the retro-labyrinthine segment realizes retro-labyrinthine approach which entirely put into sight the circumference of the bending of the lateral sinus. Thus, it is possible to perfectly and more easily deal with lesions localized in this region. The skin incision is made two fingerbreadths above and behind the external ear. The scalp uncovers the mastoid as far as the posterior ring of the external auditory canal. The superficial drilling uncovers the temporal dura, the lateral sinus and the occipital dura and between them the sinuso-dural angle. Then the mastoid is drilled away as far as the antrum is opened. Its aditus internally sided by the loop of the external semi-circular canal serves to localize the external surface of the labyrinthe. Finally, the retro-labyrinthine approach is bounded by the posterior wall of the external auditory canal anteriorly, by the external surface of the labyrinthe internally, by the dura of the superior surface of the petrous bone superiorly and by the bended part of the lateral sinus and the dura of the posterior surface of the petrous bone posteriorly. The closure is made with a dural graft then with bony dust mixed with biologic glue, then the petrectomy is plugged with under-skin fat and then the superficial planes are carefully stitched. The authors report 5 cases of meningiomas of the lateral sinus, 1 case of hemangiopericytoma and 2 dural arteriovenous fistulas which demonstrate the interest of this approach to lesions developed on this part of the lateral sinus. PMID- 2234259 TI - [Cell proliferation in human cerebral tumors. In vivo study of 45 cases by incorporation of 5-iododesoxyuridine]. AB - A method to study the proliferation of human brain tumors, is presented. Non radioactive 5-Iododeoxyuridine (2.4 gr) infused over a 24 hours period is detected in situ on histologic section by an immunological technique (peroxidase anti-peroxidase) using a specific anti-Iododeoxyuridine antibody. This exploration utilised in 45 patients is easy, reliable and harmless. All cells which enter in S phase of cellular cycle during the infusion are labelled. So the cellular kinetics of all the brain tumor cells (malignant cells, inflammatory stroma reaction cells, reactive astrocytes, endothelial and muscular cells of the vessels) are detected on the same histological section, as well as all the others proliferative cells of the body (leukocytes, primitive tumor of the metastatic brain localisation...) if multiples biopsies are done. 8 of 9 gliomas of low histological malignancy (grade I and II) have a slow cellular kinetic. The 23 astrocytomas of different histological malignancy (grade III and IV) have variable proliferative speed (7 very fast, 8 fast and 8 slow). Only the large cells of the pinealoma are very proliferative, the lymphoid stroma is quiescent. The 5 metastasis have a slow to very fast kinetic without correlation with the cellular differentiation except in one case (important differentiation and slow cellular proliferation). The 5 lymphoma cells kinetics are well correlated with the histologic differentiation (3 large cells poor differentiated lymphomas and very fast kinetic, 2 better differentiated and slower proliferation). The 2 meningiomas proliferate slowly. The biochemical and histopathological grounds of the presented method and the limits of quantification are discussed. This method is compared with this using Bromodeoxyuridine. The correlation between proliferation and histologic malignancy is analysed. The use of cytokinetic results for therapeutic and prognosis need further statistical anatomoclinical studies. PMID- 2234260 TI - [Laitinen's stereo-adapter: application to the fractionated cerebral irradiation under stereotaxic conditions]. AB - Radiosurgery is a technique which provides a single high dose of radiation very precisely to an intracranial lesion. The volume of tissue treated is small enough to avoid undue biological damage. This treatment requires very sophisticated apparatus and often considerable modifications in the treatment apparatus. The authors have closen to elaborate a system which makes it possible to deliver conventional fractionated irradiation, using a non-invasive stereotactic head frame called "Laitinen stereo-adapter". By fractionating the dose, most benign or low-grade malignant brain tumours can be treated, whatever their volume. The stereo-adapter and the target localization process are described. It can be used with C.T. scanning, angiography or M.R.I. The treatment apparatus is a linear accelerator delivering a 10 M.V. photon beam and treatment is made in the precise positioning of the target localization. The geometrical accuracy of the repeated mountings was studied in a preliminary study, showing a mean discrepancy of less than 1 mm in the three space planes. The geometrical accuracy of the radiation treatment was also studied on a phantom and the precision evaluated at less than 1 mm. The addition of extra collimators with a precollimation system decreased the lateral penumbra to 2-3 mm. Careful dosimetry was performed for each collimator. The use of non-coplanar arcs makes it possible to obtain a steep dose fall off outside the target volume. The dose planning calculations were compared to photodensitometry and thermoluminescent measurements, showing a good correlation. Each technical point will be discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234261 TI - [Multiple intracranial aneurysms: discussion of the therapeutic management of a case]. AB - The authors report the case of a 57-year-old, right-handed female who experienced a sudden acute headache, followed by a period of confusion and fever. Over the next week she developed language disturbances. No diagnosis was established. Three weeks later she was referred to the neurologist, complaining of a right frontal headache. The C.T. scans with and without contrast enhancement were suggestive of an aneurysm in each sylvian fissure. The angiography disclosed the presence of four aneurysms: a large left M.C.A. aneurysm, a larger right M.C.A. aneurysm, an aneurysm on the anterior communicating aneurysm and a small right M.C.A. aneurysm located more distally. The left M.C.A. aneurysm was presumably ruptured and responsible for the initial symptoms. The right M.C.A. aneurysms was apparently unruptured, but accounted for the persistent right headache. The other two aneurysms were thought to be asymptomatic. The left M.C.A. was operated first. Blood in the sylvian fissure confirmed the earlier rupture. Two weeks later, the three other aneurysms were surgically treated, via the same right pterional approach. No sign of hemorrhage was found on the right side. The post operative angiogram demonstrated the disappearance of all four aneurysms. Three months later, the patient was able to resume her previous occupations and clinically, she demonstrated no sign of psychological or intellectual disturbances. The management of multiple and bilateral cerebral aneurysms is discussed, as well as the management of asymptomatic aneurysms. PMID- 2234262 TI - [Mature lumbar multi-tissue dysembryoma of the spinal cord with sacral spina bifida occulta]. AB - The authors report the case of a 28-year-old woman who presented with L5 bilateral sciatica associated with perineal sensory disorders. During surgery, a mature pluritissular dysembryoma originating in a tethered spinal cord was discovered at the level of the L2-L3 intervertebral space. Following removal of the lesion, all symptoms disappeared. Mature pluritissular dysembryomas of the spinal cord result from the inclusion of neuroectodermal and mesodermal tissue which has not followed normal evolutive embryonic organization. PMID- 2234263 TI - [Hydrocephalus and cerebral cysticercosis. A case report. Review of the literature]. AB - A case of intraventricular and cisternal cerebral cysticercosis with no intraparenchymatous involvement is reported. The clinical features were characterized by episodes of blockage of the C.S.F. pathways producing acute hydrocephalus. On three occasions surgical treatment was required: two ventriculoperitoneal shunts and a ventriculocisternostomy were performed. The intraventricular cystic membranes found during the third operation suggested the diagnosis. Epidemiological arguments, the pathogenesis of hydrocephalus and diagnostic and therapeutic aspects are discussed in the light of the literature data. PMID- 2234264 TI - [Hydatidosis of the cranial vault. Two case reports]. AB - The authors report 2 cases of echinococcosis of the cranial vault, an extremely rare localization of hydatid disease. The parietal bone was involved in one case and the occipital bone in the other. The authors discuss the mechanism and classification of cranial vault echinococcosis. The clinical signs of the disease as well as its radiological appearances and especially its very characteristic CT scan appearances are studied in relation to the literature. PMID- 2234265 TI - [New strategies for the treatment of acute renal insufficiency]. PMID- 2234266 TI - [Continuous hemodialysis with low blood flow and low dialysate flow in the treatment of acute renal insufficiency]. AB - Slow continuous hemodialysis (SCHD) was performed in 9 patients with oliguric acute renal failure and cardiovascular instability. The vascular access was a Scribner's shunt in 7 patients and a double lumen venous catheter with a BSM22 blood system in 2 patients. Three different dialyzers were tested. The mean urea clearance was 10.8 +/- 1.5 ml/min with the 0.2 m2 polysulfone hollow fiber dialyzer, 14.3 +/- 2.7 ml/min with the 0.5 m2 AN 69 S parallel plate dialyzer and 13.8 +/- 1.8 ml/min with the 0.6 m2 AN 69 hollow fiber dialyzer. The mean dialysate flow rate was 15.6 +/- 1.9 ml/min, 15.2 +/- 0.7 ml/min and 15.1 +/- 1.6 ml/min for the three dialyzers, respectively. A linear relationship was documented for blood urea clearance and dialysate flow rate indicating clearly that low blood flow from 60 to 100 ml per min was appropriate for optimal diffusive transfer. The technic required continuous heparin anticoagulation. Three patients died of causes not related to the SCHD technic. When used in critically ill patients, SCHD is a simple method, suitable for intensive care unit staff with no trained dialysis nurses and allows an adequate control of uremia, fluid removal, acid base homeostasis and parenteral nutrition. PMID- 2234268 TI - [Daily hemodialysis of ultra-short duration with non-traumatic vascular access. Two cases]. AB - The authors report their experience on treating two patients, suffering end-stage renal disease, by daily hemodialysis of ultra-short duration with a non-traumatic vascular access. 90 minutes dialysis are realized 6 days a week. Clinical tolerance is excellent and patients' adhesion is satisfactory. However, despite reutilization of the dialyzer, the method remains costly. PMID- 2234267 TI - [Continuous veno-venous hemofiltration in acute renal insufficiency]. AB - A fully pump-assisted continuous veno-venous hemodiafiltration system (CVVHDF) was studied in 10 acute renal failure patients. A counter current pump system ensured slow dialysis at a mean flow rate of 24.6 +/- 0.6 ml/min (single pass) and guaranteed recovery of 97% of dialysate. Ultrafiltration rates were controlled by a separate occlusive pump, connected to the dialysate compartment. Blood was circulated by mean of a third pump at flow rates ranging form 100 to 150 ml/min. Mean duration of CVVHDF was 197 +/- 32 h (range 96-336). Mean serum creatinine and urea before initiation of CVVHDF were 525 +/- 52 mumol/l and 36 +/ 14 mmol/l and stabilized after 4-7 days of CVVHDF at 280 +/- 27 mumol/l and 14 +/- 3 mmol/l. Hemodynamic parameters remained stable. Glucose and phosphate removal by CVVHDF was 296 +/- 42 mmol/day and 33 +/- 6 mmol/day respectively. Fractional losses of aminoacids given by parenteral nutriton averaged 8 +/- 1%. An 69 filters induced no significant changes in leucocyte and thrombocyte counts and only a slight decrease in pO2 (-0.78 +/- 0.30 K Pa at 60 min). We conclude that CVVHDF is a safe, efficient and reliable treatment modality, allowing a good control of the fluid balance. PMID- 2234269 TI - [Rapid development of mitral and aortic stenoses with chronic hemodialysis. A report of 2 cases]. AB - Chronic renal failure is associated with a high incidence of calcifications of the mitral anulus, which if severe enough may result in mitral stenosis or regurgitation. Aortic valve calcifications, though less frequent, may also occur and cause aortic valve stenosis, as observed in two patients. In hemodialysed patients, identification of valvular aortic stenosis might be difficult on a clinical basis since the systolic ejection murmur might be attributed to aortic sclerosis or a high output state and left ventricular hypertrophy to previous hypertensive disease. Calcific aortic stenosis may easily be detected using echocardiography combined with the continuous Doppler technique. PMID- 2234270 TI - [Parameters of hemostasis during treatments associating fractionated heparin administered subcutaneously to standard and fractionated heparin administered intravenously in the chronic hemodialysis patient]. AB - The hemorrhagic risk of an association of fractioned heparin (Fraxiparine) injected intravenously at the dose of 7500 AXaICU or of unfractionned heparin (UFH) injected intravenously at the usual dose used for a priming dose for hemodialysis (3750 +/- 1280 IU + 1000 IU after 2 hours of dialysis) to the subcutaneous administration of a thrombo-embolism preventive dose of Fraxiparine (7500 AXaICU) was evaluated on the modifications of the following hemostasis parameters: thrombin time, Activated Partial Thrombin Time (APTT), prothrombin time, anti Xa activity in 13 uremic patients on hemodialysis. The association of intravenous and subcutaneous Fraxiparine prevents efficiently the clotting of the extracorporeal circulation without inducing a detectable antithrombinic activity. In contrast, the association of I.V. UFH to subcutaneous Fraxiparine induces a significant increase of the thrombin time and of the APTT. This latter is exclusively explained by the activity of UFH. It is concluded that subcutaneous Fraxiparine at the thromboembolism preventive dose can be associated as well to I.V. Fraxiparine as to UFH without increasing the antithrombinic activity of the plasma. PMID- 2234271 TI - [Financial impact of anemia in patients with chronic renal insufficiency undergoing hemodialysis at centers]. AB - The aim of this study was to evaluate the financial impact of anemia and transfusions in patients undergoing hemodialysis. Among a total population of 309 patients treated in 6 French hemodialysis centers, 30 have been selected to enter in a detailed evaluation: 15 (Group 2) having received in 1987 eight blood units or more, and 15 (Group 1) not transfused during the period of study. The expenditures were calculated for both groups in each category, excluding the direct cost of dialysis sessions. The analysis shows that transfused patients cost roughly 28542 FF more per capita and per year than nontransfused patients. The most important causes of increasing expenditure were not only the cost of blood units (10140 FF per patient and per year), but also direct and indirect costs of medical and biologic follow-up of transfused dialysis patients, such as outpatient visits, surgery and hospitalizations (19061 FF per capita and per year). A major center effect was evidenced, the center variation being influenced by the variation in inpatient enrollment, and variation in medical policies. Since the cost of the end-stage renal failure would be strongly affected by the costly addition of human recombinant erythropoietin to the therapeutic armamentorium, it would be advisable to take into account in economic outcomes for dialysis patients savings through reduced need for blood transfusions and perhaps fewer hospitalizations. PMID- 2234272 TI - [Continuous ambulatory peritoneal dialysis in Tunisia]. AB - CAPD covers about 4% of renal replacement therapy patients in Tunisia. From February 1983 to 1988, 47 patients, 21 males and 26 females whose mean age was 36, 14 +/- 15 were treated. Their socio-cultural level was variable. The mean duration of therapy was 14.5 months/patient/year. The five years patient survival rate was 46% and the technique survival rate 21%. Most patients had a good general condition and were professionally rehabilitated. Peritonitis was the main complication: its incidence was 1.8 episodes/patient/year. Yeasts peritonitis were relatively frequent, specially in patients who had previously been treated with antibiotics. Peritonitis was often cured with a local and general treatment. Yearly CAPD cost was 1/3 lower than center hemodialysis and a better management allowed to decrease the expenses due to laboratory and X ray investigations and to hospitalization. On the basis of this clinical experience, we believe that CAPD is an efficient and valid therapeutic modality, less expensive than hemodialysis. It is probably a suitable renal replacement therapy in other centers in Tunisia and in other developing countries. PMID- 2234273 TI - [The first thirty months of kidney transplantation in Tunisia]. AB - Kidney transplantation is actually the best replacement therapy for the end stage renal failure. It sets free the hemodialysed patient from the hemodialysis restraint and contributes to solve the socio-economic problems risen by chronic hemodialysis. The authors report the results of this technic during the first 30 months of kidney transplantation in the "Hopital Charles Nicolle" of Tunis. They describe the first steps which led to kidney transplantation, the therapeutic regimens, the medico-legal problems and the specific complications observed during this start period. PMID- 2234275 TI - [Recurring arterial thrombosis in the adult during a nephrotic syndrome. Report of a case and review of the literature]. AB - A 55 year old male with idiopathic nephrotic syndrome (minimal glomerular changes at light microscopy) developed recurrent arterial thrombosis (aortic, popliteal and prosthetic) combined with recurrent proteinuria. Fourty nine cases of adult arterial thrombosis associated with nephrotic syndrome are reviewed. This complication mainly affects the coronary, iliac and femoral, renal and cerebral arteries. Any type of nephrotic syndrome can be involved. The hypercoagulable state predisposes to thromboembolic events. Corticosteroid induced thrombotic episodes have been described during nephrotic syndrome. Therefore anticoagulant therapy is mandatory when steroid therapy is used. PMID- 2234274 TI - [Evaluation of nutritional status in chronic renal insufficiency]. AB - No nutritional criteria have been validated in uremic patients. Chronic renal failure directly alters biological nutritional criteria. Anthropometric criteria are inadequate to routine follow up, but advisable to compare groups of patients. Quantitative evaluation of nitrogen ingestion and excretion allows to control dietetic compliance. They can not be used to check long term nitrogen balance. Nutritional criteria fail to diagnose mild undernutrition in uremic patients but they help to detect patients at risk to develop undernutrition when ascribed to low protein diets. Food inquiries, conducted by well trained dietitians are quite advisable, and helpful to the patients. PMID- 2234276 TI - [Fetal and maternal risks in pregnant women with primitive chronic glomerulonephritis]. PMID- 2234277 TI - [Concentration of calcium in the dialysate and in the reinjection liquid in "on line" hemofiltration]. PMID- 2234278 TI - [Hyperkalemia induced by heparin. A case]. PMID- 2234279 TI - Acetyl-1-carnitine. 1: Effects on mortality, pathology and sensory-motor performance in aging rats. AB - Three different test sites assessed the effects of acetyl-1-carnitine (AC) on age related changes in general health, sensory-motor skills, learning, and memory. Two groups of rats began the experiments at 16 months of age. One group (OLD-AC) was given AC, 75 mg/kg/day, beginning at 16 months. The other group (OLD-CON) was treated identically except it was not given the drug. Beginning at 22 months of age, these rats and a group of young (3-4 months old) rats (YG-CON) were given a series of sensory-motor tasks. AC decreased mortality, and had no reliable effect on body weight, fluid intake, or the general health of the rats. These data indicate that a chronic dose of AC does not interfere with food and water intake, and may increase longevity. An age-related decline of performance occurred in most of the sensory-motor tasks; locomotor activity was reduced in a novel environment and in a runwheel, and the ability to prevent falling was reduced in tests on a taut wire, rotorod, inclined screen, and several types of elevated bridges. An age-related decline of performance did not occur in grooming, or in the latency to initiate several different behaviors. AC had no effect on performance in any sensory-motor task. These data indicate that the improvements produced by AC in some tests of spatial memory may be due to the effects of AC on cognitive abilities rather than on sensory-motor skills. PMID- 2234280 TI - Acetyl-1-carnitine. 2: Effects on learning and memory performance of aged rats in simple and complex mazes. AB - Acetyl-1-carnitine (AC) was administered via drinking water for six months to one group (OLD-AC) of male F-344 rats beginning at 16 months of age, while another group (OLD-CON) of rats was given water only during that period. The rats were maintained on this treatment throughout behavioral testing, which began at 22 months of age. Performance of the OLD-AC and OLD-CON rats was compared to that of young control (YG-CON) rats on the following set of tasks: spontaneous alternation in the arms of a T-maze, two-choice simultaneous discrimination in the stem of a T-maze, rewarded alternation in the arms of a T-maze, spatial discrimination and reversal on a circular platform, spatial working memory in the radial 8-arm maze, long-term memory in the 14-unit T-maze, and for preference of the light or dark chamber of a two-compartment box. AC improved the long-term memory performance in the split-stem T-maze and on the circular platform but had no discernable effects on performance of aged rats in the other tasks. Possible reasons for the selectivity of this agent's action on behavior are suggested. PMID- 2234282 TI - A comparison of the working memory performances of young and aged mice combined with parallel measures of testing and drug-induced activations of septo hippocampal and nbm-cortical cholinergic neurones. AB - The spatial working memory performances of young (2 months) and aged (24-26 months) mice of the C57BL/6 strain were compared using a delayed nonmatching to place (DNMTP) protocol in an automated 8-arm radial maze. The aged mice were observed to exhibit a selective and interference-related memory deficit. Parallel neurochemical analysis of the activity of septo-hippocampal and nbm-cortical cholinergic neurones in vivo was conducted using measures of sodium-dependent high-affinity choline uptake. Results showed that whereas the level of cholinergic activity in both brain regions varied less than 10% between young and aged mice in quiet conditions (basal) the activation usually observed at 30-sec posttest (+20-25%) in young mice was greatly attenuated in the frontal cortex and almost totally absent in the hippocampus of aged mice. In view of these results a complementary experiment was carried out in order to test the intrinsic ability of septo-hippocampal cholinergic neurones to activate using acute injection of scopolamine (1 mg/kg IP 20 min) to both young and aged mice in quiet conditions. The drug injection resulted in a very large (+70%) increase in hippocampal high affinity choline uptake and with amplitudes which did not vary significantly between young and aged subjects. These observations attest to a relatively well preserved state of central cholinergic neurones and an intact capacity to activate normally when challenged pharmacologically in aged mice. The results strongly suggest that the loss of cholinergic activation and associated memory deficit in aged mice might rather be related to a hypofunction of phasically active transsynaptic processes which normally mediate the activation of these cholinergic pathways during memory testing. PMID- 2234281 TI - Markers for biogenic amines in the aged rat brain: relationship to decline in spatial learning ability. AB - The major goal of the study was to evaluate the relationship of brain aging to individual differences in functional decline in rats. Forebrain choline acetyltransferase (ChAT) and monoamines, including their metabolites, were examined in young and aged male Long-Evans rats in relation to their spatial learning ability. Aged rats that were unimpaired on a spatial learning task exhibited few changes in neurochemistry relative to the young group: each change in this subgroup was also evident in the remaining aged animals that were behaviorally impaired. Additional changes in neurochemical measures only found in the behaviorally impaired aged animals included decreased ChAT in the basal forebrain, striatum, and frontal cortex. A cluster analysis using the 15 neurochemical measures that were sensitive to aging yielded groupings of aged animals that differed with respect to their spatial learning ability, but not in their cue learning latencies. In this analysis the activity of ChAT in the basal forebrain and striatum appeared to be the best predictors of spatial learning impairment. PMID- 2234283 TI - Disrupted retention of the classically conditioned nictitating membrane response in the aluminum-intoxicated rabbit using electrical stimulation of the brain as a conditioned stimulus. AB - Rabbits were classically conditioned to emit an eyeblink conditioned response (CR) to electrical stimulation (ESB) of the medial geniculate nucleus (MGN) paired with a corneal air puff until they attained a criterion of two consecutive days of greater than 90% CRs. They then received intraventricular injections of 1% AlCl3, HCL, or normal saline. Ten days postinjection, each animal underwent a retention test consisting of 50 ESB alone presentations. Whereas all saline and HCL animals gave at least 90% CRs during retention, no aluminum rabbit emitted more than 30% CRs. Considered with the results of previous work, these data suggest that aluminum-induced neurofibrillary degeneration disrupts retention of the CR by affecting central associative processes. PMID- 2234284 TI - The supraoptic and paraventricular nuclei of the human hypothalamus in relation to sex, age and Alzheimer's disease. AB - Volume and total cell number were determined in the supraoptic (SON) and paraventricular (PVN) nuclei of 14 male and 16 female subjects ranging in age from 10 to 93 years. In addition, 4 male and 6 female subjects suffering from Alzheimer's disease (AD) and ranging in age from 46 to 97 years were studied. Subjects were divided into two age groups, viz., "young" for subjects up to 60 years, and "old" for subjects older than 60. No sex differences in volume and in total cell number were observed in the SON and PVN in either age group. In addition, no significant correlation was found between total cell number in the SON and PVN and brain weight. No significant differences in volume and total cell number were found in either the SON or PVN between young and old control subjects or between AD cases and controls, indicating that these nuclei are spared from degenerative changes in senescence and AD. Determination of neuron numbers in the SON supported this view. In contrast, volume and total cell counts in the suprachiasmatic decreased in senescence and were dramatically reduced in AD. The present results indicate the occurrence of differential patterns of cell loss within the human hypothalamus with aging and in AD, which are proposed to be related to functional differences between the hypothalamic nuclei. PMID- 2234285 TI - Quantitative analysis of age-related dendritic changes in medium spiny I (MSI) striatal neurons of C57BL/6N mice. AB - Our study used quantitative morphometric analysis and Golgi staining methods to evaluate postnatal changes in the dendritic architecture of MSI neurons of the striatum between 1 and 30 months of age. Morphological changes and chronological age were also correlated with functional testing in order to identify subpopulations of aged mice with dendritic alterations that may be more characteristic of a motor deficit rather than the normal aging process. We found that the overall size of the dendritic arbor of MSI neurons in the rostral striatum remained stable with age, while caudal MSI neurons exhibited a significant elongation of terminal dendritic segments between 25 and 30 months of age. In addition, our correlation analysis of motor performance and chronological age found that neither striatal-motor deficits nor their associated anatomical correlates were inevitable consequences of senescence but were characteristic for a select subpopulation of aged mice with striatal-motor deficits. We found that mice that tested poorly on the balance rod had a significant increase in the number of MSI neurons with small dendritic arbors in various stages of atrophic degeneration. Conversely, 30-month-old mice that had no functional impairment showed no significant change in the number of neurons with atrophic dendrites. These data reinforce the premise that the correlation of structure and function plays an important role in the analysis of an aging population since data may vary based on the number of functionally impaired or unimpaired mice that make up an experimental group. PMID- 2234286 TI - The indusium griseum: is it involved in Alzheimer's disease? AB - The histopathology of the indusium griseum (IG), a displaced hippocampal anlage, was studied in five patients with Alzheimer's disease (AD) and five controls. In the AD group, the IG had occasional neurons with granulovacuolar change (GVD) and rare Hirano bodies (HB), but no senile plaques (SP), neurofibrillary tangles (NFT), or neurons staining for phosphorylated neurofilament antigen. There was a slight but not statistically significant diminution of neurons within the IG. In all AD cases, the hippocampus showed abundant AD-associated histopathology. In the control cases, only rare neurons with GVD were present in the IG. These findings indicate that although single neurons within the IG may show some of the cytologic changes seen in the hippocampal neurons in normal aging and AD, IG neurons do not express the full range and severity of histopathologic abnormalities characteristic of AD. This suggests that factors other than selective vulnerability of neurons of hippocampal origin might be operating to induce the neuropathologic picture of AD. PMID- 2234287 TI - Effect of exercise on physiological age-related change at mouse neuromuscular junctions. AB - To determine the effect of endurance exercise on physiological age-related change at the mouse neuromuscular junction (NMJ), synaptic function was studied for extensor digitorum longus (EDL) and soleus muscles of three C57BL/6J mouse groups, 1) young adult control (YC: 10 months), 2) old control (OC: 20 months), and 3) old mice which exercised (OE: 20 months) since young-adulthood. Electrophysiological properties were studied with intracellular recording techniques. Safety margin was studied by measuring indirect isometric twitch tension in different calcium concentrations. With sedentary aging, EDL and soleus quantal contents increased. Following aging combined with 10 months of exercise, the EDL quantal contents in OE and YC animals were similar. In contrast, soleus quantal content was greater in OE than in YC animals. Determined safety margins were OC greater than YC = OE for EDL, and OC = YC = OE for soleus. This is the first study to indicate that physiological age-related changes at NMJs of EDL and soleus muscles are affected differently by endurance exercise. Exercise prevented all physiological age-related changes in EDL NMJs but not in soleus NMJs, this suggests that EDL changes are associated with inactivity during aging, while soleus changes are "fundamental" age changes. PMID- 2234288 TI - Regulation of phorbol ester binding and protein kinase C activity in aged rat brain. AB - Protein kinase C (PKC) function was analyzed in aged male Sprague-Dawley rat brain using two different approaches: the binding of [3H]-phorbol-12,13 dibutyrate and the in vitro phosphorylation of histone H1. In cortex the binding was decreased while in cerebellum no age-related modifications were observed. In hippocampus the binding capacity was increased in old animals and the affinity decreased. The kinase activity in both soluble and particulate fractions was decreased in cortex, increased in hippocampus and unmodified in cerebellum. The area selective, age-dependent modifications in neuronal PKC may sustain short- and long-term regional changes of neuronal excitability. PMID- 2234289 TI - Aging and cognition: facilitation of recent memory in aged nonhuman primates by nimodipine. AB - Impairments of recent memory are a common complaint associated with aging and especially with respect to certain neural pathological conditions that may accompany aging. While this is well recognized, there is little clear evidence for a viable therapeutic treatment. Recently, however, certain investigations have suggested that blocking neuronal calcium channels may be an effective treatment for the memory impairments that are associated with brain injury as well as the memory failures that may occur during aging. The present research supports this suggestion by demonstrating that the dihydropyridine calcium channel blocker, nimodipine, will significantly improve the stabilized performance of 28-29-year-old rhesus monkeys when they are tested on a delayed response task which depends upon trial-specific, or recent, memory. PMID- 2234291 TI - [Combination of serial transcranial Doppler examinations and cerebral blood flow studies in the management of cerebral vasospasm after subarachnoid hemorrhage]. AB - In 13 patients who had ruptured intracranial aneurysms, serial transcranial Doppler (TCD) and cerebral blood flow (CBF) examinations were performed in order to evaluate the degree of cerebral vasospasm. All patients showed some extent of vasospasm on angiography, which was performed between Day 7 and 10. The flow velocities of either the middle cerebral arteries or the anterior cerebral arteries, measured by TCD, began to increase on post hemorrhage Day 5, and maximum flow velocities were recorded between Day 9 and 13, with normalization occurring within the following 2 weeks. In 5 cases of symptomatic vasospasm, a rapid increase of flow velocities preceded clinical manifestation of the vasospasm. Maximum flow velocities of the 5 cases were at a higher level in the range of 119-184cm/sec (mean 149cm/sec) that the cases where there were no symptoms. Consequently, serial TCD examinations were very useful for the early detection of vasospasm after subarachnoid hemorrhage. And it was confirmed that the change of flow velocities was more important than the value itself, and that the rapid increase of flow velocities indicated severe ischemia. However, for judging when vessel narrowing was resolving, the usefulness of the TCD examinations were doubtful. This is because flow velocities measured by TCD are thought to be fairly much influenced by multiple factors such as the change of blood pressure, blood volume, which were caused by the active treatment for the vasospasm. Serial measurements of CBF were also made 2-7 times (mean 3.1 times) during the first two weeks following subarachnoid hemorrhage using the 133Xe intravenous injection method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234290 TI - [Histological diagnosis of brain tumors (14): Histiocytosis X]. PMID- 2234292 TI - [Computed tomography in diagnosis of diffuse axonal injury]. AB - Diffuse axonal injury (DAI) has been described in instances of prolonged traumatic coma on the basis of the neuropathological findings, but the same findings are also found in patients with cerebral concussion. Experimental studies confirm that the quality of survivors following trauma is directly proportional to the amount of primarily injured-axon. When the injured axon lies in a widespread area of the brain, outcome for the patient is always poor. In a series of 260 severely head-injured patients, based on their poor outcome, 69 (27%) were diagnosed as DAI. Because of their relatively good outcome, eighty-two patients (32%) were classified into non-DAI group. The predominant CT finding of DAI patients was intraparenchymal deep-seated hemorrhagic lesion. This was observed in 28 patients (41%). Normal CT was also observed in 11 patients (16%). On the other hand, 8 of the non-DAI group (10%) manifested deep-seated lesions. Diffuse cerebral swelling (DCS) appeared in both groups in the same incidence. Subarachnoid hematoma in the perimesencephalic cistern (SAH (PMC] and intraventricular hematoma (IVH) were observed in 64% of the DAI group, and in 23% of the non-DAI group. The available evidence indicates that various types of hematoma seen in the deep-seated structures of the brain do not have an absolute diagnostic value, but the frequency of hematoma is thought to increase in proportion to the amount of injured-axon. PMID- 2234293 TI - [Postoperative MR findings in acoustic neuromas: nerve edema within the internal auditory canal]. AB - Postoperative MR findings of eleven acoustic neuromas were analyzed. MRI's were able to clearly visualize residual tumor around the 7th and 8th cranial nerves that were left to preserve cranial nerve function, although conventional X ray CT scans often failed to detect it due to artifacts in the parapetrous area. The facial nerves preserved during operations were also visualized from their brainstem portion to the internal auditory meatus. These findings indicate that MRI is excellent in delineating soft tissue in the CP angle that would be overlooked by conventional X ray CT scan. It was also found that the nerve bundles within the internal auditory canal gained increased signal intensity on the T1 and proton weighted images after surgical interventions and that this effect extended into the most distal end of the nerve bundles and even into the intracochlear portion of the cochlear nerve. The nerve bundles with increased signal intensity were conspicuously enhanced after intravenous administration of Gd-DTPA. This indicated that the blood nerve barrier of the nerves within the internal auditory canal were disrupted due to the surgical manipulations in excising tumors. Following such surgical manipulations, nerve edema ensued, although manipulations in the cerebello-pontine angle were done carefully and protectively under a surgical microscope. The clinical significance of disruption of the blood nerve barrier and following nerve edema were discussed from the standpoint of preservation of the 7th and 8th cranial nerve functions. PMID- 2234294 TI - [Treatment of metastatic brain tumor from renal cell carcinoma]. AB - Twenty-eight patients with metastatic brain tumor from renal cell carcinoma were treated at the National Cancer Hospital, Tokyo, between 1962 and March 1989. In 13 patients, the median time interval between the initial diagnosis and pulmonary metastasis was 18 months, and the interval between pulmonary metastasis and brain metastasis was 13 months. In 10 patients, whose initial diagnosis was pulmonary metastasis, the median interval between pulmonary metastasis and brain metastasis was also 13 months. There were 2 patients who presented brain metastasis initially. The median survival time from the diagnosis of brain metastasis was 17 months for the patients whose brain tumors were surgically resected, but only 4 months for the patients who didn't receive surgery. The median survival time of the patients who received postoperative radiation was 20 months, while it was 10.5 months for the patients who received radiation therapy alone. Repeated serial CT scans of 7 patients with measurable brain metastases revealed partial response (PR) to radiotherapy in 2 patients (28.6%), no change (NC) in 4 patients (57.2%), and progressive disease (PD) in one patient (14.3%). BrdU labeling indices of resected brain metastases were about 2%, and the doubling time calculated on repeated serial CT scans was about 20 days. As these lesions are rather resistant to radiotherapy and grow relatively slowly they should be resected as much as possible. PMID- 2234295 TI - [Clinical analysis of malignant meningiomas]. AB - It seems generally accepted that meningiomas are benign tumors, and that malignant meningiomas are not common. The pathological criteria for judging whether meningiomas are malignant or not are controversial. Hemangiopericytic type, high cellularity, brain invasion, high mitotic rate, necrotic foci, and papillary type are regarded as histological characteristics of malignant meningiomas. Of a series of 105 patients with surgically treated meningioma, 25 patients demonstrated malignant characteristics (24%). The overall recurrence rate in our patients was 14%. The incidence of recurrence in 25 patients with pathologically malignant characteristics, and recurrence in 80 patients with pathologically benign characteristics were 32% and 9%, respectively. In comparison with benign meningiomas, recurrent factors in malignant ones included Simpson grade II operation, attachment of skull base, and no radiation-therapy. In conclusion, our criteria for malignant meningiomas have proved to be acceptable, and these cases should be treated with radiation therapy after surgery. PMID- 2234296 TI - [A case of giant osteoma in the occipital bone]. AB - A 51-year-old female patient, admitted with a chief complaint of dizziness, had bulging of the occipital area, which had started insidiously. On admission, a bony hard swelling with a smooth surface was noted in the left occipital region, extending over the midline of the skull. Plain X ray films revealed a uniform shadow of an osteoid mass inside the occipital bone. A tomogram indicated that the mass originated in the diploe or outer table of the skull, although there was no evidence of destruction of the inner table. CT scan revealed mixed density mass with high density of bone and an irregularly shaped low density area. In the T1-weighted images of MRI, the entire mass showed a low intensity, while in the T2-weighted image the mass showed 3 areas with different intensities. Bone scintigraphy was performed with 99mTc-MDP and revealed an image of accumulation in the mass. Carotid and vertebral angiograms were negative for evidence of feeding arteries to the mass, for tumor stain, and for occlusion of either sigmoid sinus or transverse sinus. The mass was diagnosed as a giant osteoma, and was totally removed. The excised tumor measured 10 x 9 x 5 cm, and inspection at operation revealed it to be composed of a fragile osteoid portion and a comparatively soft connective tissue portion. The histological diagnosis of the mass was that it was a spongy osteoma including a comparatively large amount of connective tissue. The postoperative recovery of the patient was satisfactory and her dizziness disappeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234297 TI - [A case of arteriovenous malformation in a neonate]. AB - Although arteriovenous malformation (AVM) is considered a congenital disease, few cases of AVM are manifested clinically in the neonatal period. In this paper a neonatal case of AVM manifested as intracranial hemorrhage is reported. A newborn female infant 12 days after birth, was admitted to a hospital with the chief complaint of sudden onset of vomiting and fever. Neurological examination revealed left hemiparesis with bulging of the anterior fontanel. CT examination demonstrated a large mass lesion with hemorrhage in the right parietal lobe. The lesion was enhanced with contrast medium. Consent for surgery was not able to be obtained from her family, so she was treated conservatively. A gradually enlarging cyst surrounding the mass appeared in follow-up CT examination. Her left hemiparesis and bulging of the anterior fontanel remained unchanged, and a rather good general health condition was maintained. Consent for surgery was finally obtained from her parents and the patient was transferred to our hospital three months after the onset of the symptoms. Cerebral angiogram showed AVM with a big aneurysmal sac. The feeder arteries of the AVM arose from the right middle cerebral artery and the anterior cerebral artery. The drainers poured into the superior sagittal sinus. AVM was removed totally by right parietal craniotomy on the 24th January, 1989. Postoperatively, her left hemiparesis started to improve gradually. Her general condition was also good, and she showed no neurological deficits at the age of 8 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234298 TI - [Anterolateral approach to giant cell tumor in T4 vertebral body]. AB - A case of giant cell tumor involving the Th4 vertebral body is reported. A 27 year-old man, who had a 2 month history of back pain and paraparesis, was admitted to our department in August, 1986. On the first admission, he manifested severe paraparesis and sensory disturbance below the Th5 dermatome level. Neuroradiological examination demonstrated an epidural tumor involving the Th4 vertebral body and compressing the spinal cord. Emergency laminectomy for decompression and biopsy was performed. The surgical specimen was a giant-cell tumor. 6 weeks after the first operation, total removal of the tumor and anterior fusion of the Th 3-5 with iliac bone graft was performed through the anterolateral transthoracic approach. Postoperative course was uneventful. A curative resection and immediate stabilization was thus able to be undertaken through the anterolateral transthoracic approach, when the epidural tumor was confined to the thoracic vertebral body. PMID- 2234299 TI - [A case of intracranial hypoglossal neurinoma with no preoperative hypoglossal nerve palsy]. AB - A case of intracranial hypoglossal neurinoma without hypoglossal nerve palsy is reported. A 43-year-old housewife was admitted to our hospital with vertigo and left occipital headache. Neurologically, no cranial nerve deficits were present. CT scan and cerebral angiography showed a mass in the lower left posterior fossa. MRI also revealed a well circumscribed extra-axial mass compressing brain stem and cerebellum to the right. Left suboccipital craniotomy was performed and the tumor was removed subtotally. From the operative findings, the 8th to 11th cranial nerves were not related to the tumor, however, the origin of the tumor was not confirmed. The histology showed Antoni A type neurinoma mixed partially with Antoni B type. After the operation, the tongue deviation appeared to the left, but no other cranial nerve deficit was noticed. Post-operative neuroradiological reexaminations defined slight enlargement of the hypoglossal canal. Then, we concluded that the origin of the tumor must have been the hypoglossal nerve. Most intracranial hypoglossal neurinoma grow in the hypoglossal canal followed by enlargement or erosion of the hypoglossal canal. The author thought that this case suggests that this hypoglossal neurinoma originated from a few rootlets of hypoglossal nerve and grew mainly between the medulla and the hypoglossal canal. PMID- 2234300 TI - [Disproportionately large communicating fourth ventricle with bilateral exotropia: report of two cases]. AB - Two cases of disproportionately large communicating fourth ventricle (DLCFV) accompanied by consciousness disturbance and bilateral exotropia are reported. Case #1 was a 21-year-old male who suffered from consciousness disturbance and bilateral exotropia due to malfunction of the ventriculoperitoneal shunt (VPS) which had previously been operated on twice for a left parietal arteriovenous malformation, which had caused ventricular hemorrhage several times. The last hemorrhage was massive and made ventricular casting, including the fourth ventricle. Both bilateral exotropia and the fourth ventricular dilatation were well controlled by the reconstruction of the VPS. Case #2 was a 66-year-old female, semicomatous because of massive subarachnoid hemorrhage with ventricular casting hematoma due to rupture of the right middle cerebral aneurysm. Though an improvement of the consciousness disturbance was obtained by continuous ventricular drainage (CVD), bilateral exotropia and consciousness deterioration appeared after lumboperitoneal shunt followed by the removal of the CVD. Another CVD was then carried out and some improvement was obtained again. However, the same symptoms appeared again after the VPS, followed by the removal of the CVD. The patient finally died despite a third CVD. Autopsy revealed a markedly dilated fourth ventricle and massive subarachnoid clots particularly around the foramen of Magendie and Luschka. The pathogenesis of DLCFV and bilateral exotropia are also discussed. PMID- 2234301 TI - [Clinical study of pseudomembranous colitis: a neurosurgical viewpoint]. AB - In many instances patients who have undergone neurosurgery are given antibiotics. Some of these patients, however, run the risk of developing pseudomembranous colitis. In our department over the past three years, 239 patients, whose hospitalization period exceeded two weeks, were given antibiotics. Of this total number, 6 patients (2.5%) contacted pseudomembranous colitis and a clinical study of these 6 cases was conducted from a neurosurgical viewpoint. This study concentrated on diarrhea, the primary symptom, and the 6 patients consisted of 1 male and 5 females whose ages ranged from 61 to 75 years. All had undergone surgery, and a breakdown of their diseases is as follows: 2 cases of a subarachnoid hemorrhage, 2 cases of an intracerebral hemorrhage, 1 case involving a glioblastoma multiforme, and a case of normal pressure hydrocephalus. Diarrhea was present in all 6 cases and, additionally, pyrexia, abdominal pains, and leukocytosis were seen. On colonoscopic examination, 5 patients were diagnosed as having developed pseudomembranous colitis, and were treated by oral administrations of Vancomycin. In the remaining cases, in which a colonoscopic examination had not been performed, a diagnosis of pseudomembranous colitis had not been achieved and, subsequently, one patient died of multiple organ failure. On autopsy, however, it was determined that the patient had had pseudomembranous colitis. Thus, if symptoms of diarrhea occur during or after administrations of antibiotics, the possibility of pseudomembranous colitis must be assumed, and a colonoscopic examination should be performed immediately, so as to detect the disease at an early stage. This condition can be transmitted within a hospital and, therefore, great emphasis must be placed on preventing secondary infections. PMID- 2234302 TI - [Diagnostic value of short latency somatosensory evoked potentials for various intracranial lesions]. AB - Diagnostic value of short latency somatosensory evoked potentials (SSEP) was studied in 124 patients with various intracranial lesions. Abnormal SSEPs were recorded in 58 of 124 patients (46.8%) and were classified into three types. Type I (6 cases) showed abnormality of late components with N18 being preserved. All patients with type I abnormality had cortical or subcortical lesions in the parietal lobe. Type II (20 cases) was characterized by abnormality of N18 and late components with N16 being preserved, and mainly seen in patients with a lesion involving thalamus and internal capsule. Type III (31 cases) showed abnormality of N16 and N18 which was elicited by unilateral stimulation (IIIa: 11 cases), or bilateral stimulation (IIIb: 21 cases), and this indicated brainstem impairment. The incidence of SSEP abnormality was as high as 93.1% in patients with sensory disturbance, and 23.1% in patients without such disturbance, and it was suggested that SSEP is useful to detect subclinical dysfunction in the somatosensory pathway. The SSEP grades defined by Anderson et al were found to be well correlated with the outcome of patients with severe head injury, and the SSEP was more reliable for predicting the outcome of patients than the auditory brainstem evoked responses. The SSEP grades were also fairly well correlated with the outcome of patients with cerebrovascular accidents, although the outcome was not consistent in patients with moderately abnormal SSEP. PMID- 2234303 TI - [Cerebellar infarction: analysis of 33 cases]. AB - During the past 9 years and 2 months we have encountered 33 cases with cerebellar infarction. These patients were classified into 3 types according to their clinical course. Type 1 (18 cases); The course was benign, and symptoms and signs improved without surgical treatment. Type 2 (11 cases); The course was progressive with deterioration of consciousness between 24-72 hours after the onset. Type 3 (4 cases); The course was rapid resulting in lapse into coma within a few hours. Also, its prognosis was fatal due to coexisting brain-stem infarction regardless of any treatment. Surgical intervention was required for Type 2 in which the lesion included the region of the vermis or occupied more than one-third of the cerebellar hemisphere, and had subsequently compressed the brain-stem and caused obstructive hydrocephalus. In 9 cases out of Type 2, ventricular drainage alone was performed and prompt improvement of consciousness level was detected except in one case. We consider that ventricular drainage is not so invasive a method, and it is beneficial. However, in 2 cases of Type 1 and 4 cases of Type 2, hemorrhagic infarction occurred. Thus, one should be aware of the possibility of hemorrhagic infarction, even though it may be asymptomatic infarction. If prompt improvement of consciousness is not detected after ventricular drainage, suboccipital craniectomy should be recommended. PMID- 2234304 TI - [Regional effects of craniotomy on cerebral circulation and metabolism: PET study on the un-ruptured aneurysmal surgery]. AB - Regional effects of craniotomy on cerebral circulation and metabolism, such as regional cerebral blood flow (rCBF), regional cerebral oxygen consumption (rCMRO2), regional oxygen extraction fraction (rOEF), and regional cerebral blood volume (rCBV) were examined by a PET (positron emission tomography) study concerning surgery that was performed on unruptured aneurysm patients. Eight patients with intracranial un-ruptured aneurysms were studied pre- and post operatively by the 15O labelled-gas steady-state method, using HEADTOME-III. All patients underwent aneurysmal surgery performed by the transsylvian approach. There was a significant increase in the mean OEF values taken from the whole brains of 8 patients, but there was not a significant change in CBF, CMRO2 or CBV. The increase in OEF was caused by decrease of O2 content, which was caused by post-operative decrease in the Hb value. So, this OEF increase was not the direct effect of craniotomy. In 2 patients, the rCBF and rCMRO2, in the fronto temporal region (where craniotomy was performed) increased post-operatively. This regional effect suggests transient reactive hyperemia following compressive ischemia during the operative procedure, and metabolic demands for recovery of brain function. In 2 other patients, who had relatively low rCBFs during the pre operative study, rCBF and rCMRO2 in the bi-frontal region had decreased more at the post-operative study. This change appears to have been caused by removal of cerebrospinal fluid and depression of the frontal lobe. From this study, it becomes evident that the regional effect of craniotomy on cerebral circulation and metabolism is not so great, when adequate microsurgical techniques are used. PMID- 2234305 TI - [A case of pineocytoma totally removed]. AB - A case of pineocytoma which is thought to be uncommon is reported. A 50-year-old man complaining of occasional dizziness and tinnitus of the left ear was referred to our Center on Feb. 10, 1989. No noteworthy signs were detected out neurologically. Plain CT scan disclosed a homogeneous iso- to high-density area in the pineal region, which was markedly enhanced on the post-contrast study. On the T1 MRI, that pineal tumor appeared as a low intensity area and on the T2, a high intensity area with intratumoral low signal intensity suggesting calcification. The tumor was conspicuously enhanced by Gd-DTPA. Left vertebral angiography demonstrated a faint tumor blush which was confirmed to be fed by the medial and the lateral posterior choroidal and the thalamo-perforating arteries bilaterally. The superior thalamic and the internal cerebral veins were displaced upwardly and the precentral cerebellar vein posteriorly. On Feb. 20, the tumor was totally removed via infratentorial-supracerebellar approach. Histological examination of the removed tumor disclosed that it was a "true" pineocytoma. The patient was discharged on Mar. 15 and has been free from signs and symptoms by the 4th postoperative month. Neither irradiation nor chemotherapy was added. Literature concerned are reviewed and brief discussion on pineocytoma done. PMID- 2234306 TI - [A case of traumatic syringomyelia which disappeared after anterior decompression: a suggestion for surgical treatment of syringomyelia]. AB - A 37-year-old man had received cervical spinal-cord injury 20 years previously. Recently, he complained of progressive spastic gait and was shown to have fracture dislocation of the C5 vertebral body which compressed the spinal cord posteriorly. He also had a syrinx from the C5 to C2 vertebral level. Postoperatively, this syrinx disappeared after anterior decompression of the C4 and C5 vertebral bodies. Such a case as this has never been reported, and this case may give a suggestion for surgical treatment of syringomyelia, because it is very natural that the most reasonable treatment of any disease is removal of the cause. PMID- 2234307 TI - [Complete occlusion of right middle cerebral artery by radiation therapy after removal of pituitary adenoma: case report]. AB - Radiation angiopathy is a well-known complication accompanying irradiation. But the majority of effected vessels are small vessels. Cases of intracranial major arteries being effected are not so numerous. We report the case of a 47-year-old female patient. The removal of pituitary adenoma was carried out on her in 1982. After that, 4500rad irradiation was performed. It was about six years after irradiation that the first angiography was made. Right MCA occlusion, multiple stenosis of both ACAs and Moya-Moya like vessels were discovered. On admission light paresis on her left lower extremity was recognized and hyperlipidemia was noted. It was interesting that the multiple stenosis was found in an area outside the irradiation field. MCA-STA anastomosis was performed and the prognosis was good. The authors described this case and reviewed the pertinent literature. PMID- 2234308 TI - [Cerebellar ganglioglioma: a case report]. AB - A case of cerebellar ganglioglioma in a 5 year-old girl is presented. She came to our hospital on January 30, 1989 with complaints of headache of one year duration. CT scans disclosed a low density lesion suggesting a cystic tumor in the left cerebellar hemisphere with moderate hydrocephalus. Preoperative MRI demonstrated more clearly the location and extent of the tumor. She was operated on using suboccipital craniotomy, on March 3. Subtotal removal of the tumor was performed because the tumor had invaded the brain stem. She made an uneventful recovery without any neurological deficits. Histologically, the tumor was composed of ganglion cells and astrocytic cells, so it was diagnosed as ganglioglioma. Cerebellar ganglioglioma is a rare tumor, and only 17 cases have been reported including the present case. Clinical and radiological study of these cases revealed that there are no specific findings to indicate cerebellar ganglioglioma and preoperative diagnosis is impossible. But practically, MRI is the most sensitive method for identifying the extent of the lesion and, thus, is of benefit for deciding operative strategy. PMID- 2234309 TI - [Aneurysm arising from the cortical branch of the superior cerebellar artery: case report]. AB - We reported a case of a 64-year-old man who presented a subarachnoid hemorrhage due to rupture of an aneurysm arising from the cortical branch of the superior cerebellar artery (SCA) at the junction of the superior vermian branch and the hemispheric branch. Eight days after the rupture, neck clipping of the aneurysm was performed successfully using the occipital transtentorial approach in a prone position, and the patient's postoperative course was uneventful. This rare case of aneurysm arising from the cortical branch of SCA was discussed with a review of literature. PMID- 2234310 TI - [A case of large basal ganglia AVM totally removed by staged operation]. AB - Large basal ganglia AVMs have been deemed inoperable because of their location in critical structures. Nonetheless, the unfavorable natural history of an untreated ruptured AVM in a young patient induced us to approach these lesions. We presented a case of a large basal ganglia AVM totally removed by a three-staged operation. A 26-year-old man who had twice experienced intracranial hemorrhage was admitted for examination. On admission, mild left hemiparesis, hypesthesia and left hemianopsia were disclosed. CT scan showed the AVM was located in the posterior thalamus with the hematoma cavity laterally. Right carotid and vertebral angiograms demonstrated a large AVM, 5cm in diameter, supplied by the anterior choroidal artery (AchoA), the lateral lenticulostriate arteries (I LSAs), the lateral posterior choroidal artery (LPchoA) and the thalamo perforating artery. Drainage was via the internal cerebral vein and the basal vein of Rosenthal. MRI demonstrated more clearly the anatomical relationship of the nidus and surrounding structures. The patient underwent a three staged operation. At the first operation AchoA was interrupted in the inferior horn of the lateral ventricle (IHL) via the hematoma cavity using the trans-sylvian approach. The anterior part of the nidus was dissected with all except one of the I-LSAs being disconnected. At the next operation by occipital interhemispheric approach, some feeders from the posterior cerebral artery were coagulated and disconnected. The medial and posterior part of the nidus was dissected from the thalamus along with the choroid plexus of the trigone of the lateral ventricle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234311 TI - Glutathione S-transferase in human brain. AB - The glutathione S-transferases are a complex group of multifunctional enzymes which may detoxify a wide range of toxic substances including drugs and carcinogens. Different isoenzymes vary in substrate specificity, tissue distribution and level of expression during development. Following reports of cell-specific and age-dependent expression in rat brain we have studied, immunohistochemically, expression of the Pi and Alpha class isoenzymes in 10 adult and 21 human fetal brains. Whilst Alpha isoenzyme is expressed only in adult brain, and then only focally, Pi isoenzyme is strongly expressed from as early as 12 weeks gestation. In the adult, expression is localized to choroid plexus, vascular endothelium, ventricular lining cells, pia-arachnoid and astrocytes. In fetal brain, expression is also strong in cells with the morphology of tanycytes and in the cell bodies of radial glia. Neurons are consistently negative. Pi isoenzyme thus localizes to the sites of the blood-CSF barrier, blood-brain barrier, CSF-brain barrier and pia-arachnoid-brain barrier. It is ideally placed to regulate neuronal exposure to potentially toxic substances derived from blood or cerebrospinal fluid. Expression so early in gestation is of significance and may imply a role in protection of the developing human brain. PMID- 2234312 TI - Spinal cord disease in children with HIV-1 infection: a combined molecular biological and neuropathological study. AB - An autopsy study was performed on spinal cords from 18 children who died with HIV 1 infection, using standard histopathologic techniques as well as in situ hybridization and immunocytochemistry for HIV-1. Of 16 spinal cords examined by histology, nine had inflammatory cell infiltrates and six had multinucleated cells; both types of lesion are associated with the presence of HIV-1 in central nervous system tissue. HIV-1 type lesions were often present in the spinal cord and brain from the same patient. Pallor of myelin in corticospinal tracts in the cord was present in half of the cases; this change correlated with diffuse myelin pallor in the corresponding brains, but not with the HIV-1 associated changes in the cords. In situ hybridization for HIV-1 nucleic acid sequences gave positive results in seven of 18 spinal cords, with hybridizing signal usually localized to inflammatory cell infiltrates and multinucleated cells. Positive in situ hybridization, on frozen sections, correlated with the presence of HIV-1 associated changes on paraffin sections from the same cases. Immunocytochemistry for p25 core protein of HIV-1, using a monoclonal antibody on frozen sections, was positive in multinucleated cells, macrophages, and microglia. In this series there were two cases of vacuolar myelopathy, one a 30-month-old boy who had concomitant measles virus in the spinal cord grey matter, and the other nine-year old girl who had severe HIV-1 infection of the cord. Other than the single case of measles virus, there were no opportunistic infections in the cords in this series. HIV-1 frequently involves the spinal cord in children with AIDS, while opportunistic infections are rare. Vacuolar myelopathy occurs in children with HIV-1 infection, although its occurrence is much less frequent than in adults with AIDS. PMID- 2234313 TI - Pathology of Streptococcal meningitis following intravenous intracisternal and natural routes of infection. AB - The distribution of pathological lesions present in 20 cases of naturally occurring Streptococcus suis type 2 meningitis and 20 cases of the disease induced experimentally by intravenous or intracisternal inoculation was examined. It was found that the distribution of lesions was similar; mild lesions were present at the choroid plexuses whilst the most dense cellular accumulations were found at sites of cerebrospinal fluid (CSF) efflux, such as arachnoid villi and olfactory nerve sheaths. The distribution of changes was considered to reflect the dynamics of CSF flow rather than indicate the site of entry of the organisms into the CSF compartment. PMID- 2234314 TI - Brainstem auditory evoked potentials in icteric fullterm newborns: alterations after exchange transfusion. AB - Brainstem auditory evoked potentials (BAEP) were studied in five fullterm newborns before and during an exchange transfusion (ET) for hyperbilirubinemia and 1, 24, 48 hours after, in order to evaluate the changes of BAEP following acute decreases in bilirubinemia. Hyperbilirubinemia was due to ABO incompatibility. The newborns were free of other risk factors known to alter BAEP. In comparison with our normal laboratory data, we observed significant differences in pre-ET recordings for latencies I and V (p less than 0.01), and for interpeak latency V-III (p less than 0.01). After ET, there was a tendency towards shortening of all mean latencies and interpeak latencies in correlation with the acute decrease in bilirubinemia, but post-ET BAEP alterations consisted predominantly of a wave V latency and of a wave V-I interval shortening (p less than 0.01). In four patients, during the 48 hours post-ET we observed modifications of the wave V-I interval related to variations of bilirubinemia. At 12 months, BAEP were normal. Even acceptable increase of bilirubinemia in otherwise normal newborns may have a deleterious influence on BAEP and this could have implications for the determination of a so-called threshold of bilirubin neurotoxicity. Our results suggest that bilirubin neurotoxicity is rapidly reversed by ET, but it seems important to verify BAEP in the follow-up of hyperbilirubinemic newborns. PMID- 2234315 TI - Analysis of very long-chain fatty acids and plasmalogen in the erythrocyte membrane: a simple method for the detection of peroxisomal disorders and discrimination between adrenoleukodystrophy and Zellweger syndrome. AB - We analyzed the sphingomyelin very long-chain fatty acids (VLCFAs) and phosphatidylethanolamine (PE) plasmalogen contents of the erythrocyte membrane in patients suffering from peroxisomal disorders. In a patient with Zellweger syndrome, both a decrease in the PE plasmalogen content and an increase in the sphingomyelin VLCFAs content of the erythrocyte membrane were noted. In patients with adrenoleukodystrophy, however, there was no decrease in PE plasmalogen, although the sphingomyelin VLCFAs content of the membrane was significantly increased in comparison with control values. Analyses of both sphingomyelin VLCFAs and PE plasmalogen were carried out simultaneously, using both the same process and the same sample. PMID- 2234316 TI - Fetal ventriculomegaly due to isolated brain malformations. AB - Management of 32 consecutive cases of fetal hydrocephalus diagnosed prenatally during a five years period is presented. Thirteen cases (40%) being patients with ventriculomegaly due to isolated brain malformation are the topic of this paper. In this group, management was conservative and consisted of termination of pregnancy by elective cesarean section after prenatal fetal assessment. Agenesis of corpus callosum (6 cases) and Dandy-Walker malformation (7 cases) were the most common observed forms. Antenatal sonography improved intrauterine follow-up. Skillful perinatal management and support facilities after birth have been found a reliable approach to conservative management of fetal hydrocephalus by lacking of satisfactory techniques for in utero permanent cerebrospinal fluid shunting. PMID- 2234317 TI - Acute hemiparesis as the presenting sign in a heterozygote for ornithine transcarbamylase deficiency. AB - Strokes in children occur in conjunction with cardiac disease, hematological disorders, trauma, intracranial infections and migraine. Recently several inborn errors of metabolism have been recognized as possible causes of stroke-like symptoms. We describe a female heterozygote of ornithine transcarbamylase deficiency, who presented with convulsions and right sided hemiplegia. MR-imaging of the brain demonstrated an acute ischemic lesion in the left hemisphere. In addition to other known metabolic causes of stroke like attacks urea cycle defects should be considered in the differential diagnosis of acute hemiplegia in childhood. PMID- 2234318 TI - The role of short latency somatosensory evoked responses in infants with rapidly progressive ventricular dilatation. AB - The effect of hydrocephalus on somatosensory evoked potentials was studied in nine infants. An increase in N1 latency was found in five infants studied longitudinally during a period of progressive ventricular dilatation. A marked decrease in N1 latency was noted in 7 infants, within one week following shunt insertion and in two infants who showed spontaneous arrest of ventricular growth. A correlation was found between cerebrospinal fluid pressure and the delay in N1 latency, but the number of infants studied is still small. SEPs appear to be a useful additional test when assessing infants with progressive ventricular dilatation. Once a baseline value for N1 has been obtained following shunt insertion, SEPs may subsequently be useful when assessing a child with possible shunt dysfunction. PMID- 2234319 TI - N-acetylaspartic aciduria in Canavan disease: another proof in two infants. AB - Increased amounts of urinary N-acetyl-aspartic acid was found in two infants with biopsy proven Canavan disease. The aspartoacylase assay is a new tool for determining both the prenatal and antenatal diagnosis of Canavan disease. This assay should be screened in patients with early onset of psychomotor deterioration, macrocephaly, spasticity/hypotonia and white matter hyperleucency at CT scan. PMID- 2234320 TI - MR-imaging findings in children with Sturge-Weber syndrome. AB - Intracranial extent and distribution of leptomeningeal angiomatosis, visualized by magnetic resonance imaging (MRI) with Gadolinium-DTPA (Gd-DTPA) enhancement, is demonstrated in four children with Sturge-Weber syndrome (SWS). Aged 7, 9, 11 and 19 months, they presented with cutaneous, neurologic and ocular symptoms at the time of MRI examination. Angiomatous alteration of the skull, atypically located and congested intracerebral and basal veins as well as intracerebral changes secondary to the leptomeningeal angiomatosis are demonstrated with T2 weighted images. Gd-DTPA enhanced T1 weighted images exhibit clearly the regional distribution of angiomatosis in the skull, meninges and within the brain. Before calcifications in children with SWS are detectable by CT, MRI is the method of choice to detect intracranial involvement. Enhancement with Gd-DTPA improves the diagnostic value of MRI, before neurological symptoms appear. Follow-up studies with Gd-DTPA enhanced MRI can be applied to recognize thrombotic changes of leptomeningeal angiomatosis as well as subsequent intracerebral impairment. PMID- 2234321 TI - An incident case-referent study of febrile convulsions in children: genetical and social aspects. AB - In a prospective community-based study of 103 children with febrile convulsions (FC), social and genetical factors were compared with 193 age and sex matched referents sampled from the community. FC were found more often among parents of cases than referents (odds ratio 21.0; p less than 0.001). A history of FC in any type of relative was found in 39.8% of cases and 10.4% of referents (odds ratio 5.8; p less than 0.001). The familial occurrence of FC is best described by a multifactorial (polygenic) model. No difference was found between groups in the occurrence of other diseases than FC affecting the central nervous system and only one case was mentally retarded. No difference was found between cases and referents in the age of independent walking and ability to speak at age 18 months. Children with FC more often had infectious diseases than referents (odds ratio 2.84; p = 0.002). Children with FC more often lived in apartments and spent their time in day by day care institutions (odds ratio 2.91; p = 0.02). Parents' occupation did not differ between groups. Mothers of children with FC more often had compulsory education only compared with mothers of referents. PMID- 2234322 TI - Cutaneomeningo-spinal angiomatosis: the syndrome of Cobb. A case report. AB - We present the case of a young patient with Cobb's syndrome who presented with an acute paraplegia. A review of the literature indicates that this condition is rare. The coexistence of cutaneous naevi in a dermatomal pattern and neurological signs of a spinal cord lesion is significant and should always be considered as the excision of spinal arteriovenous malformations can be accomplished safely. PMID- 2234323 TI - Moya-Moya syndrome and primary pulmonary hypertension in childhood. AB - A child is described with Moya-Moya disease and a primary pulmonary hypertension. This association has never been reported until now. It is attempting to consider a common vascular denominator for both diseases although we were not able to prove this hypothesis. PMID- 2234324 TI - Megalencephaly with dysmyelination, spasticity, ataxia, seizures and distinctive neurophysiological findings in two siblings. AB - A progressive neurological condition characterised by megalencephaly, spasticity, ataxia and seizures in two siblings of consanguineous parents is described. The electroencephalogram showed posterior discharges and an unusual photoparoxysmal response whereas brainstem auditory evoked potential findings were consistent with a white matter disorder. Computerized tomography scans revealed diffuse hypodensity of the white matter and a brain biopsy on one sibling showed features of dysmyelination without evidence of demyelination, Rosenthal fibres or the spongy changes characteristic of Canavan's disease. There was no detectable biochemical abnormality. This combination of clinical, neurophysiological and neuropathological abnormalities has not previously been described. PMID- 2234325 TI - Thickness of carotid artery atherosclerotic plaque and ischemic risk. AB - Noninvasive duplex scanning of carotid artery atherosclerotic plaque was performed in 286 consecutive patients referred to a cerebrovascular diagnostic laboratory. The presence and thickness of such plaque in the region of the carotid bifurcation were examined for association with the degree of vessel stenosis, age, sex, smoking history, history of prior transient ischemic attack or stroke, and systemic manifestations of atherosclerotic disease. Atherosclerotic plaque thickness was positively correlated with degree of vessel stenosis (P less than 0.0001). Both parameters were independent predictors of cerebrovascular events but plaque thickness was a better predictor of prior transient ischemic attacks (P less than 0.05), and vessel stenosis was a better predictor of prior stroke (P less than 0.005). Patient age (P less than 0.001) and pack-years of cigarette use (P less than 0.001) were independent positive predictors of carotid atherosclerotic plaque thickness. The greatest effect of smoking and atherosclerotic plaque thickness was seen in heavy smokers younger than age 55. Both carotid artery plaque thickness and pack-years of smoking were significant independent predictors of other systemic manifestations of atherosclerotic disease (P less than 0.05). Such noninvasive scanning of carotid artery atherosclerotic plaque demonstrates the significant role of age and smoking in the progression of disease. It also suggests a significant role for carotid atherosclerotic artery plaque in the pathophysiology of cerebrovascular events, especially transient ischemic attacks, even prior to the production of a flow-limiting stenosis. Finally, noninvasive screening of carotid artery plaque may provide a useful marker for the patient at risk for systemic atherosclerotic disease and identify the patient for whom maximal atherosclerotic risk factor modification is needed. PMID- 2234326 TI - A rat femoral artery model for vasospasm. AB - A new animal model for vasospasm using rat femoral artery has been developed. Whole blood, washed erythrocytes, or leukocytes in platelet-rich plasma were selectively applied to the adventitial surface of the femoral artery for 7 days in 15 rats, after which the vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. As compared with matched control arteries, there was a prominent reduction in luminal cross sectional area after 7 days in vessels exposed to whole blood or washed erythrocytes, but not in those exposed to leukocytes in platelet-rich plasma. In arteries with luminal narrowing, light and transmission electron microscopy demonstrated marked morphological changes throughout the vessel wall similar to those seen in cerebral vasospasm after subarachnoid hemorrhage. Immunohistochemistry disclosed a prominent loss of immunoreactive actin in smooth muscle cells of arteries exposed to whole blood or erythrocytes. To assess the time course of arterial narrowing in this model, whole blood was selectively applied to the adventitial surface of femoral arteries in 23 rats for periods from 2 to 20 days. As compared with control arteries, arterial narrowing was variably present at 2 days, progressively increased by 5 days, was maximal at 7 to 10 days, and returned to near control levels by 20 days. The presence and severity of ultrastructural changes in vessel wall corresponded to the degree of arterial narrowing over time. These results suggest that chronic narrowing in rat femoral artery exposed to periadventitial blood is analogous to that observed in cerebral arterial vasospasm after subarachnoid hemorrhage. This new model represents a simple and reliable means to investigate pathogenic mechanisms and potential therapies for vasospasm. PMID- 2234327 TI - Effect of endothelin on the canine basilar artery. AB - Endothelin, a recently discovered peptide produced by endothelial cells, has been shown to have potent constrictor effects on major arteries in vitro. This experiment was performed to determine whether endothelin plays a physiological role in cerebral vasospasm after subarachnoid hemorrhage. A cisternal injection of endothelin (10(-8) mol or 10(-9) mol) caused severe vasoconstriction of the canine basilar artery. The degree of vasoconstriction was dose related and long lasting, persisting for more than 24 hours. This constriction was prevented completely by pretreatment with nicardipine (10(-8) mol). Endothelin produced a marked and transient elevation in blood pressure and might play an important role in cerebral vasospasm. Further investigation will be needed to determine the role of endothelin in the pathogenesis of vasospasm. PMID- 2234329 TI - Acute changes in the dynamics of the cerebrospinal fluid system during experimental subarachnoid hemorrhage. AB - Early changes in intracranial pressure (ICP), ICP volume index, and resistance to absorption of cerebrospinal fluid induced by experimental subarachnoid hemorrhage were studied in cats. After SAH, the ICP was slightly elevated, and there was a decrease in the buffering capacity of the intracranial space and a sharp rise in outflow resistance. During infusion of blood into the cisterna magna with a constant infusion rate, an extensive increase in ICP could be demonstrated in contrast to the infusion of saline, which caused only slight elevation of ICP. Furthermore, during blood infusion, the ICP level did not reach a plateau phase of pressure, as was demonstrated during infusion of saline. It is suggested that the marked increase in ICP during blood infusion into the subarachnoid space is caused by intracranial volume loading and the simultaneous increase in cerebrospinal fluid outflow resistance. It is concluded that the reported relationship between increased cerebrospinal fluid outflow resistance and increased ICP supports the hypothesis of a strong increase in ICP during subarachnoid hemorrhage in human subjects. PMID- 2234328 TI - The frequency-dependent behavior of cerebral autoregulation. AB - Cerebral autoregulation is a complex physiological process composed of both fast and slow components that may respond differently to different rates and patterns of blood pressure variation. To assess the temporal nature of autoregulation, transcranial Doppler velocity recordings of the middle cerebral artery obtained over prolonged periods were compared with blood pressure recordings in 5 patients without cerebral disease and in 13 patients with intracranial pathological changes. Correlations between the velocity and pressure wave forms at various frequencies of variation were measured with systems analysis techniques. Patients with aneurysmal subarachnoid hemorrhage had high correlations indicating pressure dependent flow and impaired autoregulation. Patients without cerebral disease had significantly lower correlations (P less than 0.01), indicating intact autoregulation. Examples of increasing correlations and correlations at new frequencies emerging as the clinical condition worsened are given. These preliminary examples suggest that the application of systems analysis techniques to velocity and pressure data allow measurement of the temporal nature of cerebral autoregulation. PMID- 2234330 TI - Inhibition of tumor growth in a glioma model treated with boron neutron capture therapy. AB - This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2. Ten rats, serving as controls, received no treatment either before or after tumor implantation. A second group of 10 rats was treated with BNCT 4 days before tumor implantation; these animals received no further treatment. The remaining group of 10 rats received no pretreatment but was treated with BNCT 10 days after implantation. Histological and ultrastructural analyses were performed in 2 animals from each group 17 days after implantation. Survival times of the untreated control animals (mean, 25.8 days) did not differ statistically from the survival times of the rats in the pretreated group (mean, 25.5 days). The rats treated with BNCT after implantation survived significantly longer (P less than 0.02; mean, 33.2 days) than the controls and the preirradiated animals. Tumor size indices calculated from measurements taken at the time of death were similar in all groups. These results indicate that, with this tumor model, BNCT does not cause a tumor bed effect in cerebral tissue. The therapeutic gains observed with BNCT result from direct effects on tumor cells or on the peritumoral neovascularity. PMID- 2234331 TI - Characterization of a newly established malignant meningioma cell line of the human brain: IOMM-Lee. AB - A permanent malignant meningioma (MM) cell line of the human brain designated "IOMM-Lee" is reported. This cell line was successfully established from the tumor of a 61-year-old Chinese man with repeated recurrent primary intraosseous malignant meningioma of the skull. It has been subcultured for more than 60 passages during the past 30 months. The doubling time of cultured cells is approximately 62 hours. Tumorigenicity in athymic nude mice (Balb/c-nu/nu) who develop multiple pulmonary metastases was observed; the doubling time of tumor volume in vivo is approximately 5 days. Karyotypic analysis revealed this cell line to be of human origin and near-diploid, with a modal chromosome number of 49. The mesenchymal tumor marker vimentin and intracytoplasmic microfilaments were identified in the cytoplasm of tumor cells by indirect immunohistochemical peroxidase-anti-peroxidase assays and immunogold ultrastructural localization by transmission electron microscopy, respectively. Scanning electron microscopy of cultured cells and xenografted tumors revealed ellipsoidal or carrot-shaped tumor cells presenting a wrinkled surface with short sparse microvilli. Potential proliferating activity was determined by Ki-67 monoclonal antibody; the Ki-67 labeling index of cultured cells and xenografted tumors was approximately 36% and 30%, respectively. This newly established malignant meningioma cell line of the human brain may prove useful as a research model. PMID- 2234332 TI - Repair of isolated axillary nerve lesions after infraclavicular brachial plexus injuries: case reports. AB - Stretch injuries of the infraclavicular brachial plexus have a much better prognosis for spontaneous recovery than do their supraclavicular counterparts. We present three patients with stretch injuries of the infraclavicular brachial plexus who had spontaneous restoration of function in all muscles except the deltoid. Decreased shoulder abduction was a serious handicap to these individuals. At surgical exploration, each patient had an isolated, complete axillary nerve disruption at the quadrilateral space. Deltoid muscle function was restored in all three patients by repair of the axillary nerve with sural nerve grafts across the quadrilateral space. PMID- 2234333 TI - Functional results of facial nerve suture after removal of acoustic neurinoma: analysis of 25 cases. AB - The facial nerve is sometimes severed during the removal of acoustic neurinomas, either intentionally to ensure complete removal, or unintentionally because of difficulties in identification. In such cases we have, if possible, sutured the nerve stumps microsurgically, either end to end or by use of an intervening nerve graft. We analyzed the outcome of 25 instances of facial nerve suturing in a series of 219 patients operated on for acoustic neurinoma from 1979 to 1987. The first signs of recovery appeared at an average of 12 months, and there was continued improvement for several years. Recovery was graded from 1 to 6. The anastomosis was successful in 24 of the 25 sutured nerves, in that at least some facial movement and tone were restored (Grade 5 or higher). In 11 of the 25 cases, facial appearance at rest and with movement was moderately good (Grade 2 or 3). A Grade 1 result, with no perceivable facial dysfunction, was never achieved. Typically, oral muscles showed the most improvement and frontal muscles the least. Facial appearance was better at rest than with movement, which was always complicated by some degree of synkinesis. Closure of the eye was so good in 13 of the 25 cases that neither tarsorrhaphy nor an eyelid spring was necessary. When the facial nerve is severed, intraoperative suture is recommended, because it provides a chance for moderately good restoration of facial appearance. PMID- 2234334 TI - Extracranial repair of cerebrospinal fluid fistulas: technique and results in 37 patients. AB - Although neurosurgeons have traditionally preferred intracranial repair for the management of cerebrospinal fluid (CSF) fistulas, this approach is associated with the complications of a craniotomy, anosmia, and a high incidence of recurrent fistulas. Extracranial repair, on the other hand, produces no central nervous system morbidity, preserves olfaction, and is associated with a low incidence of recurrence. Although there have been several reports of extracranial repair of CSF fistulas by otorhinolaryngologists, this approach has received scant mention in the neurosurgical literature. We report here our experience with 37 patients with CSF rhinorrhea or otorrhea who underwent extracranial repair. The etiology of the fistula was postoperative in 22, traumatic in 6, and spontaneous in 9. The fistulas were repaired using one of four techniques: external ethmoid-sphenoid in 18 patients, transmastoid in 9, transseptosphenoid in 7, and osteoplastic frontal sinusotomy in 3. In 32 of the 37 patients (86%) the fistulas were successfully repaired with the initial procedure. Of the 5 patients requiring a second operation, the fistula was successfully closed in 4 for an overall success rate of 97%. Complications were few and consisted of a transient facial paresis in a patient undergoing transmastoid repair and one death from meningitis. The authors conclude that because of low morbidity and mortality and a high success rate in closing fistulas, extracranial repair is the preferred technique for the operative management of CSF rhinorrhea and otorrhea. PMID- 2234335 TI - Whither short-course chemotherapy for tuberculous meningitis? AB - Short-course chemotherapy is well established for the treatment of pulmonary tuberculosis but not for extrapulmonary disease. We present a series of 35 cases in which chemotherapy for tuberculous meningitis was given for a period of less than 2 years. Short-term therapy was associated with recrudescence of tuberculous meningitis and, in some cases, with the development of deep cerebral infarcts and permanent neurological deficits. We think short-term chemotherapy for tuberculosis of the central nervous system is inadequate. PMID- 2234336 TI - Mild head injury classification. AB - Inconsistencies across studies concerning outcome after mild head injury may reflect differences in the diagnostic criteria used for selection of patients. Consequently, we compared the neurobehavioral outcome in three groups of consecutively hospitalized patients (aged 16 to 50 years) who sustained a closed head injury (CHI) and had a Glasgow Coma Scale (GCS) score in the 9 to 15 range. These groups included patients with uncomplicated CHI with mild impairment of consciousness as reflected by a GCS score in the 13 to 15 range (n = 78), patients with initially mild impairment of consciousness complicated by brain lesion or depressed skull fracture (n = 77), and patients with moderate CHI (n = 60). Tests of memory, information processing, and verbal fluency were administered within 1 to 3 months after injury, and the Glasgow Outcome Scale was completed at 6 months. Neurobehavioral functioning was impaired in the groups with complicated mild CHI and moderate CHI as compared to the group with uncomplicated mild CHI. Although moderate CHI produced longer durations of impaired consciousness and posttraumatic amnesia than complicated mild head injury, patients in these groups did not differ in neurobehavioral performance. Global outcome at 6 months was better in the patients with mild CHI than in patients with complicated mild and moderate injuries. Analysis of the various complications of mild CHI revealed that the presence of an intracranial lesion was related to more severe neurobehavioral sequelae than injuries complicated by a depressed fracture. PMID- 2234337 TI - Diffuse axonal injury: analysis of 100 patients with radiological signs. AB - One hundred patients with head injuries who showed diffuse axonal injury on computed tomographic scans are reported. Evaluation of the Glasgow Coma Score, pupillary signs, and computed tomographic findings on admission led to an improved ability to forecast outcomes. Our relatively good results as compared with other series, can be explained by the high proportion of children and by the liberal use of computed tomography to evaluate head injuries, thus revealing that concussion may sometimes be regarded as an early form of diffuse axonal injury. PMID- 2234338 TI - Ischemic brain damage in a model of acute subdural hematoma. AB - Ischemic brain damage is the most important neuropathological finding in humans who die after acute subdural hematoma; however, its causes are poorly understood. We have produced acute subdural hematoma in the rat by injecting 400 microliters of autologous blood (approximately 20% of intracranial volume) into the subdural space. Extensive areas of ischemic damage, involving 14 to 16% of the volume of the hemisphere, developed in this model at 4 and 24 hours after the lesion. The hematomas were associated with a brief peak in intracranial pressure (51 mm Hg), which remained at three times normal levels (14 mm Hg) for 3 hours. In this model, therefore, ischemic damage appears to be due to the local effects of blood overlying the cortex at 4 hours after the ictus, rather than to globally raised intracranial pressure. The implications for the pathophysiology of acute subdural hematomas in humans are discussed. PMID- 2234339 TI - Stroke: a selective history. PMID- 2234340 TI - Chronic Lyme disease with an expansive granulomatous lesion in the cerebellopontine angle. AB - Expansive granulomatous lesions in the posterior cranial fossa are rare and have not been reported in conjunction with Lyme disease. We report a patient with verified Borrelia burgdorferi infection who developed a tumor in the cerebellopontine angle. Rapid growth of the tumor led to signs of cerebral compression and to hydrocephalus. Surgical intervention was required despite florid meningitis. The histological examination showed inflammatory, nonspecific granulation tissue. The origin of this tissue is almost certainly causally related to the B. burgdorferi infection. Signs of inflammation resolved rapidly after subtotal resection. The clinical, radiological, and biochemical course is documented. This is the first report of an expansive cerebral lesion in the chronic phase of Lyme disease. PMID- 2234341 TI - Symptomatic pineal cyst: case report. AB - Pineal cysts are being described with increasing frequency since the advent of magnetic resonance imaging. Although pineal cysts are incidental findings in as many as 4% of magnetic resonance imaging studies, symptomatic pineal cysts are quite rare. We present a case of pineal cyst causing aqueductal obstruction with symptomatic hydrocephalus and resultant headache and syncope, which was treated by surgical resection. A review of the relevant literature and discussion follow. PMID- 2234342 TI - Vagal schwannoma associated with syncopal attacks and postural hypotension: a case report. AB - A case of vagal schwannoma in the cerebellomedullary angle is reported. Preoperatively, the patient had paroxysmal episodes of postural hypotension with syncope. After total removal of the vagal tumor, her systemic blood pressure returned to normal. PMID- 2234343 TI - Multiple intracranial tumors of different cell types. AB - Multiple intracranial tumors of different cell types are rare. We report nine patients with multiple intracranial tumors, who did not have a history of trauma, irradiation, or phacomatosis. The clinical, radiological, and histopathological findings as well as indications for operations in patients with asymptomatic second tumors are discussed. PMID- 2234344 TI - Occult vascular malformations of the optic chiasm: magnetic resonance imaging diagnosis and surgical laser resection. AB - Angiographically occult vascular malformations of the optic nerve and chiasm are extremely rare. Before the advent of magnetic resonance imaging (MRI), it was difficult to diagnose these lesions preoperatively. We report MRI scan findings of optic chiasm cavernous angiomas in two patients with chiasmal syndrome. MRI was useful in localizing the vascular malformation and delineating its characteristics, especially chronic hemorrhage. One patient underwent biopsy of the lesion. The other patient underwent complete microsurgical resection of the malformation with the carbon dioxide laser with preservation of vision. Occult vascular malformations of the optic nerve and chiasm may be a more common cause of visual deterioration than previously recognized. The MRI scan is the imaging modality of choice for diagnosing and following these lesions. In certain patients, these vascular malformations may be amenable to complete surgical removal with stabilization or improvement of visual function. PMID- 2234345 TI - Cyst of the choroid plexus in the lateral ventricle: case report and review of the literature. AB - We report an intraventricular cyst in a 2-year-old boy who had myoclonic jerks of the extremities. The cyst had no communication with the ventricular system or subarachnoid space. Total removal of the cyst adhering to the choroid plexus was accomplished. The glial cyst wall was lined in part by flattened or cuboidal epithelium. The preoperative and postoperative computed tomographic scans and magnetic resonance images are presented, and congenital benign cysts in the lateral ventricle are reviewed and discussed. PMID- 2234346 TI - Traumatic aneurysm of the superior cerebellar artery: case report and review of the literature. AB - Less than 10% of the 250 reported cases of traumatic intracranial aneurysms have involved the posterior circulation. Traumatic aneurysms of the superior cerebellar artery are extremely rare, with only three cases previously reported. This is the first report of a traumatic superior cerebellar artery aneurysm in which the diagnosis was suggested by computed tomographic scan. The potential for a good outcome suggests the value of early angiography when the history and diagnostic imaging studies suggest the possibility of a traumatic aneurysm. PMID- 2234347 TI - Intradural herniation of a thoracic disc presenting as flaccid paraplegia: case report. AB - A case of intradural herniation of a thoracic disc in a patient with a flaccid paraplegia is described. Intradural herniation of a thoracic disc is considered a rare event. A review of the relevant patient literature revealed 14 other reports involving 28 patients. No other report has described a patient with an intradural thoracic disc herniation who developed a flaccid paraplegia. PMID- 2234348 TI - A case of dyschondroplasia associated with brain stem glioma: diagnosis by stereotactic biopsy. AB - We present a 24-year-old patient with multiple chondromas of both hands, the pelvis, the left leg, and an associated brain stem glioma. There was no evidence of hemangioma or dyschromia, and the condition was diagnosed as Ollier's disease, a special type of dyschondroplasia like Maffucci's syndrome and Kast's disease. An increased overall risk for development of malignant skeletal and nonskeletal tumors is associated with Maffucci's syndrome. The risk of malignant degeneration is lower in Ollier's disease. A glioma in the pons and the right lobe of the cerebellum was found in this patient. The literature describes an association with gliomas in only 12 cases of dyschondroplasia and an infratentorial localization in just one case. Signs of malignancy were histologically confirmed in 7 cases without significant preponderance of any one type. Our patient had a low-grade brain stem astrocytoma with fibrillar and gemistocytic components. A stereotactic serial biopsy made it possible to rule out malignant degeneration. Stereotactic brain tumor biopsy as a routine neurosurgical procedure is particularly valuable for deep space-occupying processes and forms the basis for therapy. In the present case, irradiation was not recommended. PMID- 2234349 TI - An unusual complication of silastic dural substitute: case report. AB - A case is presented in which a patient developed an unusual complication after the use of Silastic dural substitute. In 1983, the patient underwent removal of a meningioma with the involved dura. Five years later, he developed around the graft material a very thick connective tissue capsule, which simulated a recurrent meningioma clinically and radiologically. PMID- 2234350 TI - Decompression of lumbar spinal stenosis. PMID- 2234351 TI - Prediction of outcome of shunt procedures for communicating hydrocephalus. PMID- 2234352 TI - Ultrastructural evidence for differentiation in a human glioblastoma cell line treated with inhibitors of eicosanoid metabolism. AB - Human glioblastoma cells incubated in the presence of inhibitors of eicosanoid biosynthesis show decreased cellular proliferation without cytotoxicity. We studied the ultrastructural morphology of a human glioblastoma cell line cultured with nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, or 5,8,11,14 eicosatetraynoic acid, a cyclooxygenase and lipoxygenase inhibitor. When glioblastoma cells were treated for 3 days with antiproliferative concentrations of either agent, they shared many morphological characteristics, including evidence for increased astrocytic differentiation with only limited signs of toxicity. The inhibited glioma cells demonstrated an increase in the number and length of astrocytic processes containing greater numbers of glial filaments, and the NDGA-treated cells also demonstrated extensive lateral pseudopod formation along the processes. The glioblastoma cell shape also became more elongated, losing the usual nuclear lobularity and nuclear inclusions, especially in NDGA treated cells. Many cytoplasmic organelles packed the cytosol of the inhibited glioma cells, including prominent Golgi apparatus, dilated smooth endoplasmic reticulum evolving into dilated vesicles, cytoplasmic vacuoles, and numerous concentric laminations. There was limited evidence for toxicity, however, as the mitochondria were more pleomorphic with some mitochondrial distention and disruption of the cristae along with an increase in cytoplasmic vacuolization. We conclude that the inhibitors of eicosanoid biosynthesis, NDGA and 5,8,11,14 eicosatetraynoic acid, not only suppress glioblastoma cell proliferation, but also induce increased astrocytic differentiation. PMID- 2234353 TI - Epidermoid tumors of the 4th ventricle: report of seven cases. AB - Epidermoid tumors occur very rarely in the 4th ventricle. We discuss the history, clinical course, and the surgical results for seven patients. One patient had a remittal of symptoms, probably due to the emergence of the tumor from the 4th ventricle into the cisterna magna. Total removal of the capsule was possible only in the youngest patient. At present, four patients (mean follow-up, 6 years) enjoy good general and neurological health. PMID- 2234354 TI - Limited selective posterior rhizotomy for the treatment of spasticity secondary to infantile cerebral palsy: a preliminary report. AB - A limited selective posterior rhizotomy was performed on 30 children suffering from spasticity secondary to infantile cerebral palsy. As opposed to standard techniques that stimulate and divide the dorsal rootlets from L2 to S1, we dissected L4, L5, and S1 dorsal roots through an L5 to S1 laminectomy. Eight to 12 rootlets from each root were electrically stimulated with two unipolar electrodes (pulse width, 50 microseconds; 10-50 V). The muscle responses were observed visually and registered by electromyography. Those rootlets associated with an abnormal motor response as evidenced by sustained muscular contraction or by prolonged electromyographic response were divided. Spasticity was scored from 0 to +. The muscular groups assessed were those involved in the flexion of the shoulder, elbow and wrist in the upper limbs, and those involved in flexion and adduction of the hip, flexion of the leg, and plantar flexion in the lower limbs. The patients were assessed 1 week before and 6 months after the operation. Reduction of spasticity was observed in all the muscular groups, and all the patients presented functional improvement of motor abilities. These preliminary results indicate that a limited procedure that reduces the extension of the laminectomy and the length of the operation could be effective for treating spasticity secondary to infantile cerebral palsy. PMID- 2234355 TI - Radical osteoclastic craniectomy in sagittal synostosis. AB - We report our experience in the surgical treatment of sagittal synostosis using radical osteoclastic craniectomy in 60 consecutive patients. After surgery in children aged 6 months or younger (Group I), reossification usually started 2 weeks postoperatively and was complete within 6 months, resulting in an optimal skull contour. In children aged 7 to 12 months (Group II), reossification was prolonged and lasted for 12 months or longer. The skull contour normalized in its biparietal width and improved in sagittal diameter, remaining, however, slightly abnormal. In children older than 12 months (Group III), the skull contour partly improved in the biparietal diameter but did not change in the sagittal direction. Reossification was incomplete with persistent pseudosutures. Enlarged frontal subarachnoid spaces were reversible or improved in all patients independent of age at the time of surgery. We encountered no complications in our series. In our opinion, radical osteoclastic craniectomy is the simplest, most efficient, and most physiologically sound method for the treatment of sagittal synostosis in patients up to 6 months of age. This procedure allows the rapidly growing brain to form its skull vault, thus providing optimal cosmetic results. In older children, osteoplastic morcellation procedures should be the treatment of choice. PMID- 2234356 TI - Serial ultrasonographic evaluation of neonatal vein of Galen malformations to assess the efficacy of interventional neuroradiological procedures. AB - Two-dimensional echocardiography complemented with color-flow imaging and pulsed Doppler ultrasound was used to evaluate one fetus and five neonates with a vein of Galen malformation who had severe high-output congestive heart failure and cranial bruits at birth. Intracranial blood flow through the vein of Galen malformations, cardiac status, and direction of aortic blood flow were assessed before and after staged interventional neuroradiological treatment with transarterial and transvenous embolization procedures. Color-flow imaging in each infant displayed the major vascular anatomy including feeding vessels and the patterns of filling of the vein of Galen malformations. Pulsed Doppler ultrasound performed on the descending aorta above the diaphragm showed the degree of diastolic flow reversal indicative of runoff into the vein of Galen malformations. A reduction in blood flow through the vein of Galen malformation was seen on color-flow imaging in four patients treated successfully by embolic procedures. The ratio of diastolic retrograde flow velocity in the descending aorta to systolic antegrade velocity decreased from 0.51 +/- 0.15 (mean +/- standard deviation) to 0.15 +/- 0.20 (P less than 0.05). Color-flow imaging and pulsed Doppler ultrasonography provided anatomical and pathophysiological information regarding cardiac hemodynamics and intracranial blood flow; with the patient's clinical status, these methods provided a reliable, noninvasive means to evaluate the effectiveness of therapy and the need for further treatment in neonates with vein of Galen malformations. PMID- 2234357 TI - Spinal cord thromboplastin-induced coagulopathy in a rabbit model. AB - Coagulopathy results from many diverse events, including several neurogenic causes. Using a rabbit model, we produced coagulopathy by injecting autologous spinal cord and extracted thromboplastin intravenously. Serial coagulation panels were performed to evaluate the activation of the thrombotic and fibrinolytic pathways. Group 1 animals (n = 4) received intravenous injections of homogenized spinal cord tissue. Coagulopathy was not produced with 36 mg of homogenized spinal cord tissue, but 50 mg or more resulted in death. Group 2 animals (n = 12) received intravenous injections of extracted rabbit cord thromboplastin, which contained approximately 60% activity of a commercially purified rabbit brain thromboplastin. Five animals receiving 2.5 to 5.5 mg of thromboplastin per kilogram of body weight survived with evidence of coagulopathy. Seven animals receiving 2.5 to 100 mg of thromboplastin per kilogram of body weight died. Group 3 (4 control animals) received normal saline injections without changes in clinical or laboratory status. The thrombotic pathway was activated in all animals as evidenced by decreased platelet counts and fibrinogen levels. Activation of the fibrinolytic system was demonstrated by increased concentrations of protamine sulfate and abnormal euglobulin clot lysis times. The most sensitive parameters were the platelet count, protamine sulfate concentration, and white cell count (margination), which became abnormal within 15 minutes after the injections and returned to normal within 1 hour. PMID- 2234358 TI - Xenon-enhanced computed tomographic measurement of cerebral blood flow in patients with chronic subdural hematomas. AB - We compared clinical symptoms with extent of brain shift on computed tomographic (CT) scans and quantitative and three-dimensional measurements of cerebral blood flow (CBF) on xenon-enhanced CT scans in 10 patients with chronic subdural hematomas. Five patients had only headache and minimal or no brain shift on a CT scan. The other five had hemiparesis and/or mental disturbance in addition to headache and moderate or severe brain shift on a CT scan. The mean hemispheric CBF decreased about 7% in patients with headache and about 35% in patients with hemiparesis and/or mental disturbance. It decreased also on the side without the hematoma. The CBF reduction was always more pronounced in the putamen and thalamus than in the cortex. On the contrary, the cortex CBF was mostly preserved or even elevated in both groups of patients. We speculate that CBF reduction in patients with a chronic subdural hematoma occurs initially in central cerebral areas like the basal ganglia and thalamus, and then extends to the entire hemisphere including the cortex as brain compression and displacement progress. Central cerebral area involvement might be more responsible for clinical symptoms than the cortex. PMID- 2234359 TI - Infectious intracranial aneurysms: comparison of groups with and without endocarditis. AB - A series of 12 patients with infectious intracranial aneurysms is presented, and a number of unusual features of the disorder are emphasized. A comparison of characteristics of the aneurysms and clinical course is made between patients with and without infective endocarditis. Most of the unusual characteristics of infectious aneurysms, including rare locations, causative organisms, and predisposing medical conditions, occurred in the group without endocarditis. The relationship of atypical features of infectious aneurysms to the etiology of aneurysm formation is discussed, and an approach to treatment is presented. PMID- 2234360 TI - Distribution of angiographic vasospasm after subarachnoid hemorrhage: implications for diagnosis by transcranial Doppler ultrasonography. AB - A study was undertaken to determine how frequently angiographic vasospasm occurs outside the normal access range of transcranial Doppler ultrasound in patients who have suffered a subarachnoid hemorrhage. Vasospasm located in the basal vessels is readily identifiable using transcranial Doppler ultrasound whereas spasm affecting the more distal, vertically oriented arteries is outside the standard detection range. It is therefore speculated that the sensitivity of the technique would be adversely affected by a high incidence of distal vasospasm. A total of 136 angiograms performed on 68 patients after a subarachnoid hemorrhage from anterior circulation aneurysms were reviewed to determine the typical distribution of vasospasm. Of the 40 cases that showed greater than or equal to 25% vessel narrowing, 50.0% had spasm restricted to the basal vessels, 42.5% had spasm involving both basal and distal segments, and 7.5% had spasm of the distal segments only. None of the patients with distal vasospasm alone developed delayed ischemic deficits. It is concluded that most patients with anterior circulation aneurysms who develop vasospasm will have involvement of the basal vessels, but a small number of patients may develop vasospasm only in distal vessels. PMID- 2234361 TI - Hypertension as a risk factor for epilepsy after aneurysmal subarachnoid hemorrhage and surgery. AB - A prospective, consecutive series of 307 patients with aneurysmal subarachnoid hemorrhage ranging from Grades 1 to V according to the classification of Hunt and Hess on admission were evaluated to determine the incidence of epilepsy 1 to 3 years (mean, 1.4 years) after aneurysmal subarachnoid hemorrhage (SAH) and surgery. Sixty-three patients had died and one patient was lost to follow-up. Twenty-nine patients developed epileptic seizures after the SAH and surgery. The mean time from the SAH to epileptic seizure varied from 0 days (day of the SAH) to 2 years (mean, 6.7 months). The seizures were classified as focal in 9 patients (31%) and as generalized in 20 patients (69%). All patients received anticonvulsant medication after more than one seizure. The risk factors for development of posthemorrhagic/postoperative epilepsy were, in order of importance: a history of hypertension; an infarct on late computed tomographic scan; and the duration of coma after the ictus. Of the 85 patients with histories of hypertension, 17 (20.0%) developed epilepsy. Only 12 (5.4%) of the 222 nonhypertensive patients developed epileptic seizures. The difference between the groups was significant (P = 0.0001). Computed tomographic scans were undertaken in 237 patients 1 to 3 years (mean, 1.4 years) after the SAH and surgery. Postoperative epilepsy was significantly associated with infarcts visualized on computed tomographic scan (P = 0.0005). PMID- 2234362 TI - Pharmacological reversibility of experimental cerebral vasospasm. AB - Using a morphometric technique, the pharmacological reversibility of luminal narrowing after experimental subarachnoid hemorrhage (SAH) was investigated. For vasodilation, a "cocktail" consisting of 10(-4) M papaverine, 2 x 10(-4) M sodium nitroprusside, and 10(-5) M adenosine was administered intra-arterially. Forty two rabbits were divided into six groups: control (normal animals); control plus cocktail (normal animals perfused with the cocktail before fixation); SAH (animals sacrificed 48 hours subsequent to intracisternal injection of 1.5 ml/kg of arterial blood); SAH plus cocktail (SAH plus perfusion with the cocktail); BaCl2 (animals sacrificed 10 minutes after intracisternal injection of 2 ml of 3 x 10(-3) M BaCl2); and BaCl2 plus cocktail (BaCl2 animals perfused with the cocktail). The diameter of the basilar arteries in the control and the control plus cocktail groups was not significantly different. BaCl2 reduced the diameter 44% and SAH reduced the diameter 27%. There were no significant differences between the diameter of the BaCl2 plus cocktail group and SAH plus cocktail group when compared with the control or the control plus cocktail group. Morphological examination by light and transmission electron microscopy showed luminal narrowing and corrugation of the elastic lamina with few degenerative or proliferative changes of the vessel wall in animals with SAH. These results suggest that cerebral vasospasm is caused initially by smooth muscle contraction rather than by proliferative vasculopathy and that it is not an irreversible process. PMID- 2234363 TI - Changes in intracochlear and intracanalicular nerves after acoustic neurinoma excision confirmed by magnetic resonance imaging. AB - Postoperative magnetic resonance imaging findings related to the vestibulocochlear and facial nerves within the internal auditory canal were analyzed in acoustic neurinomas. T1- and proton-weighted magnetic resonance images showed that the vestibulocochlear nerves distal to the internal auditory meatus increased in signal intensity after surgical intervention. These nerves were conspicuously enhanced after intravenous administration of gadolinium diethylene-triamine-pentaacetic acid. The preserved facial nerves were also markedly enhanced postoperatively. As a possible cause of these findings, we suggest operative disruption of the blood-nerve barrier with ensuing nerve edema, although the operative procedures were carefully carried out using a surgical microscope. The clinical significance of traumatic disruption of the blood-nerve barrier and subsequent nerve edema are discussed from the standpoint of preservation of cochlear nerve function. PMID- 2234364 TI - Fractures of the clivus: classification and clinical features. AB - Fractures of the clival complex were diagnosed in a series of 17 patients admitted to the Maryland Institute for Emergency Medical Services System and the University of Maryland Medical System over a 30-month period. These fractures were divided pathologically into three types based upon their appearance on computed tomography: longitudinal, transverse, and oblique. The mechanisms of injury were similar in all groups, and the Glasgow Coma Scale scores at admission were comparable, regardless of fracture type, in survivors and nonsurvivors. Longitudinal fractures were associated with severe injury to the central nervous system and with brain stem infarction, and 4 of 6 (67%) of these patients died. Transverse fractures of the clival complex were found in 6 patients, 3 of whom (50%) died. All of these patients had fractures of the petrous ridge; 2 of the 3 survivors had multiple cranial nerve deficits, and one patient developed a carotid-cavernous fistula. Of the 5 patients with oblique clival fractures, 2 survived (40%), both of whom had multiple cranial nerve palsies; in addition, one of these patients developed a carotid-cavernous fistula. Using the present generation of computed tomographic scanners, fractures of the clival complex can be reliably diagnosed; they are probably more common than previously believed and can be separated into three groups based on the characteristics on computed tomographic scans and clinical findings. PMID- 2234365 TI - Effect of dosage and timing of administration of naloxone on outcome in the rat ventral compression model of spinal cord injury. AB - The effect of the dosage and timing of administration of naloxone after spinal cord injury in rats via the ventral compression technique is presented. The rat ventral compression technique allows for a ventral compression of the spinal cord without the requirement of a previous laminectomy. It therefore facilitates the creation of an experimental lesion that is similar to that observed in the human clinicopathological situation. The first part of the two-part study presented herein involved the determination of the optimal dose of naloxone, administered intraperitoneally 45 minutes after the creation of the lesion. Of the groups studied (control group through 10.0 mg/kg group), 2.0 mg/kg of naloxone proved to be superior to both lesser and greater dosages. The second part of the study involved the administration of a 2.0 mg/kg dose of naloxone at varying intervals ranging from 10 minutes before lesioning to 24 hours after lesioning. A multiphasic response was again demonstrated, with an optimal time of administration occurring 45 minutes after the creation of the lesion. A significant effect was offered by a midrange dose of naloxone (2.0 mg/kg), administered at 45 minutes after injury (P less than 0.02 by analysis of variance and Duncan's multiple range test). These findings are discussed with respect to recent evidence regarding the effects of narcotic antagonists on both mu and kappa narcotic receptors. Past and future experiments must account for these responses to multiphasic dosage and timing of administration. Failure to do so may lead to erroneous conclusions. PMID- 2234366 TI - Harvey Cushing and pediatric neurosurgery. AB - Harvey Cushing made fundamental and seminal contributions to pediatric neurosurgery. Early in his surgical career, he described the diagnosis and treatment of subdural hematomas in newborn infants. Important investigations on the cerebrospinal fluid and the nature of hydrocephalus were carried out under his direction, first by Walter Dandy and Kenneth Blackfan in the Hunterian Laboratory at the Johns Hopkins School of Medicine, and shortly afterward by Lewis Weed at the Laboratory of Surgical Research at Harvard. Cushing's principle interest throughout his professional career was the surgical treatment of brain tumors. By his careful clinical examination of patients. Cushing described for the first time a typical and composite picture of the more common tumors of the posterior fossa in children, particularly the cerebellar astrocytomas and medulloblastomas. Percival Bailey, working under Cushing's supervision at Harvard, studied and classified the glioma group of brain tumors. This contribution by Bailey was a major factor in the understanding of the characteristics and natural history of these tumors. In the closing years of Cushing's surgical practice, he published three major papers summarizing the characteristics, clinical picture, and treatment of the more common brain tumors in the pediatric age group. As a result of his exceptional surgical skill and innovations, he was able to achieve a surgical mortality of only 4% in operations on brain tumors in children. These landmark papers secured Cushing's place as a pioneer in pediatric neurosurgery. PMID- 2234367 TI - Clinicopathological experience with pineocytomas: report of five surgically treated cases. AB - The clinicopathological experience associated with five cases of pineocytoma is presented. All patients were treated by surgical removal without postoperative radiotherapy. In three individuals, 2000 cGy was administered to the tumor as a presurgical diagnostic test, with no evidence of response. All cases demonstrated histological features of pineocytoma, according to the criteria of Borit et al., and of the so-called "pineocytoma with neuronal differentiation," according to the criteria of Rubinstein. The experience obtained from the present series reveals that these tumors can occur in the initial decades of life, that a cystic appearance and the presence of calcifications are distinctive features of their radiological evaluation, and that they have a good prognosis after surgical removal, even when the histological data indicate local invasion. The convenience of reserving the term "pineocytoma" for these tumors, and of including the so called "pineocytomas without further differentiation" within the group of pineoblastomas, is suggested in order to achieve a practical clinicopathological assessment of parenchymatous pineal tumors. PMID- 2234368 TI - Maffucci's syndrome with bilateral cartilaginous tumors of the cerebellopontine angle. AB - Maffucci's syndrome is characterized by the combination of multiple enchondromas (Ollier's disease) and hemangiomatosis. These hemangiomas develop in the subcutaneous tissue and form red-blue tumors dispersed over the whole body. Intracranial involvement is rare, making a preoperative radiological diagnosis and differentiation from other tumors rather difficult. The radiological characteristics and successful removal of the intracranial part of a chondrosarcoma of the cerebellopontine angle in a case of Maffucci's syndrome are reported in this paper. PMID- 2234369 TI - Concurrent intradural and extradural meningiomas of the cervical spine. AB - A case of an extradural spinal meningioma presenting with a separate intradural meningioma at the same cord level is reported. Review of the English literature on spinal epidural meningiomas reveals a high incidence of concurrent intradural tumors in patients with epidural meningiomas. This leads to the conclusion that the intradural space should be evaluated carefully when an epidural meningioma is encountered. PMID- 2234370 TI - Intradural spinal cord tumor presenting as a subarachnoid hemorrhage: magnetic resonance imaging diagnosis. AB - Negative findings on four-vessel angiography after a subarachnoid hemorrhage are seen in 5 to 30% of patients. A previously silent lesion in the spinal canal may be responsible for the ictus in a small percentage of this group. The etiological factors include tumors and arteriovenous malformations; however, investigations of such lesions have been limited to patients with signs and symptoms of spinal cord or nerve root pathological processes. This report describes the management of a 56-year-old woman with clinical findings typical of an aneurysmal subarachnoid hemorrhage and negative findings on cerebral angiography, in whom magnetic resonance imaging with gadolinium enhancement revealed an intradural extramedullary cervical schwannoma. For this reason, cervicothoracic magnetic resonance imaging with gadolinium enhancement should be considered as an adjunctive scanning examination in all patients with a subarachnoid hemorrhage and negative findings on angiography. PMID- 2234371 TI - Myelopathy presenting decades after surgery for congenital cervical cutaneous lesions. AB - We report on two patients in whom cervical myelopathy developed decades after they had undergone surgery for congenital cervical cutaneous lesions. Preoperative magnetic resonance imaging demonstrated dorsal tethering and cavitation of the cervical cord in the area of the previous surgery and was helpful in decision making regarding surgical exploration and in planning for it. We stress the importance of long-term follow-up by both clinical examination and magnetic resonance imaging in children who have been operated on for cervical cutaneous masses that may have central connections. PMID- 2234372 TI - Paraplegia after a routine lumbar laminectomy: report of a rare complication and successful management. AB - Arachnoid cysts of the spinal canal are relatively common lesions that may be either intra- or extradural. These cysts are usually asymptomatic but may produce symptoms by compressing the spinal cord or nerve roots. We report a case in which an intradural thoracic arachnoid cyst became symptomatic after a routine decompressive lumbar laminectomy for spinal stenosis. Myelography revealed no abnormality, although magnetic resonance imaging and computed tomography after myelography demonstrated a mass within the posterior aspect of the thoracic spinal canal associated with anterior displacement and compression of the spinal cord. A change in the flow dynamics of the cerebrospinal fluid probably allowed the development of spinal cord compression due to one of the following: expansion of the cyst, decreased cerebrospinal fluid buffer between the cord and the cyst, or epidural venous engorgement. A concomitant and more cephalad lesion such as an arachnoid cyst should be considered when myelopathic complications arise after lumbar surgery. Magnetic resonance imaging and computed tomography after myelography are useful to demonstrate the additional pathological processes. PMID- 2234373 TI - Radiation necrosis of the optic chiasm, optic tract, hypothalamus, and upper pons after radiotherapy for pituitary adenoma, detected by gadolinium-enhanced, T1 weighted magnetic resonance imaging: case report. AB - A 26-year-old woman was treated for a prolactin secreting pituitary adenoma by surgery and radiotherapy (5860 rads). Fourteen months later, she developed right hemiparesis and dysarthria. A T1-weighted magnetic resonance imaging scan using gadolinium contrast showed a small, enhanced lesion in the upper pons. Seven months later, she had a sudden onset of loss of vision, and radiation optic neuropathy was diagnosed. A T1-weighted magnetic resonance imaging scan showed widespread gadolinium-enhanced lesions in the optic chiasm, optic tract, and hypothalamus. Magnetic resonance imaging is indispensable for the early diagnosis of radiation necrosis, which is not visualized by radiography or computed tomography. PMID- 2234375 TI - Suprasellar pituitary adenoma arising from the pars tuberalis: case report. AB - A rare case of suprasellar pituitary adenoma arising from the pars tuberalis in a 53-year-old woman is presented. The tumor was located exclusively above the diaphragma sellae, and no invasion into the sella turcica was noted. PMID- 2234374 TI - Pituitary hemorrhage into a Rathke's cleft cyst. AB - This report describes a case of symptomatic pituitary hemorrhage into a Rathke's cleft cyst in a 25-year-old woman. The literature on pituitary hemorrhage in nonadenomatous sellar tumors is reviewed. PMID- 2234376 TI - An operative complication in a patient with a true posterior communicating artery aneurysm: case report and review of the literature. AB - Intraoperative oculomotor nerve injury in a patient with a true posterior communicating artery aneurysm is reported in detail. A comparison of internal carotid artery aneurysms at the posterior communicating artery junction with true posterior communicating artery aneurysms deserves special attention, because the vascular relationships of the aneurysm are more complex. A clip along the internal carotid artery does not occlude blood flow to the aneurysm, and the aneurysmal neck and the distal posterior communicating artery are closer to the oculomotor nerve. This is the 27th reported case of a true posterior communicating artery aneurysm. The incidence of true posterior communicating artery aneurysms ranges from 0.1 to 2.8% of all aneurysm patients. Such aneurysms constitute 4.6 and 11% of so-called posterior communicating aneurysms in two series. Difficulty associated with a preoperative diagnosis has been documented in at least 4 cases. An awareness of this rare aneurysm is stressed in order to avoid operative complications. PMID- 2234377 TI - A method for monitoring intracerebral temperature in neurosurgical patients. AB - Current interest in brain temperature and selective brain cooling makes a method allowing for continuous monitoring of intracerebral temperature in humans desirable. The authors describe a safe, simple, and reliable technique using a thermocouple of copper and constantan in combination with intraventricular monitoring of intracranial pressure for measurement of brain temperature in neurosurgical patients. PMID- 2234378 TI - Adult hydrocephalus and shunting. PMID- 2234379 TI - Spinal epidural hematoma and garlic ingestion. PMID- 2234380 TI - Osteochondroma of the vertebral column. PMID- 2234381 TI - Indomethacin in severe head injury. PMID- 2234382 TI - Clinical utility of partial flip angle T2-weighted spin-echo imaging of the brain. AB - To assess the clinical usefulness of partial flip angle (PFA) spin-echo (SE) brain imaging, a total of eighty patients were examined with both conventional double echo T2-weighted SE (2500/30, 80/90 degrees/one excitation) and PFA double echo SE (1200/30, 70/45 degrees/two excitations) on 2.0T system. Two comparative studies were performed: (1) in 65 patients PFA SE technique was compared with conventional SE without flow compensating gradients, and (2) in 15 patients the former was compared with the latter with flow compensating gradients. Imaging time was nearly identical in each sequence. In both studies we found that PFA T2 weighted SE images were almost identical to those obtained with the conventional SE technique in the contrast characteristics and the detection rate of the abnormalities (100%, 85/85 lesions), and more importantly, PFA SE revealed few flow artifacts in the brain stem, temporal lobes and basal ganglia which were frequently seen on conventional SE without flow compensating gradients. Additionally, PFA SE images demonstrated no suppression of CSF flow void in the aqueduct which was commonly seen on conventional SE with flow compensating gradients. In overall image quality, the PFA SE images, particularly the second echo images, were almost comparable with those of conventional SE with flow compensating gradients. A flip angle of 45 degrees seems to be close to Ernst angle, the angle at which maximum signal occurs, for a given TR of 1200 msec for CSF and most of the abnormalities containing higher water content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234383 TI - Value of contrast enhanced CT scanning in the non-trauma emergency room patient. AB - To determine the value of performing contrast CT in addition to non-contrast CT in the evaluation of acute non-traumatic central nervous system disorders, we retrospectively reviewed 322 cases originating from the emergency room at our institution. The most common indication for scanning was seizure activity (34% of total), followed by headache (30%), focal neurological deficit (10%), and altered mental status (8%). 75% of the non-contrast scans were normal. The contrast enhanced scan revealed abnormalities not evident on the non-contrast scan in only three of these cases, and the information did not alter patient management. We conclude that in the acute setting, if a non-contrast CT is normal, a contrast study is usually unnecessary. Therefore, given the additional risks of contrast infusion, the contrast study, if needed, is generally best obtained at a later date, after more careful evaluation of the patient's history and medical records. If the non-contrast CT scan is abnormal, a contrast enhanced CT scan may be beneficial, but, again, is often not needed to direct acute patient management. PMID- 2234385 TI - Dissecting and fusiform aneurysms of vertebro-basilar systems. MR imaging. AB - The magnetic resonance (MR) findings of three cases with vertebro-basilar dissecting aneurysms (DA) were compared with those of two cases with vertebro basilar fusiform aneurysms (FA). No abnormal findings, excepting a dilatation of a signal-void area corresponding to the arterial blood flow, were shown on the MR images in the patients with a FA. In contrast to the FA cases, various abnormalities were detected by the MR studies in all three DA cases. An intimal flap and a double lumen were demonstrated in one case. An intra-mural hematoma was shown in one case. A hematoma neighboring the parent artery was demonstrated in two cases. MR imaging was thought to be useful for detecting intracranial vascular lesions, such as a DA, and for discriminating between a DA and a FA. PMID- 2234384 TI - Pediatric brainstem glioma. Post-radiation clinical and MR follow-up. AB - Thirty-four pediatric patients, twenty with presumed and fourteen with biopsy or autopsy proven brainstem gliomas were imaged by CT and MR before radiation therapy. Twenty-eight patients received radiotherapy. Of these, eighteen fit the protocol for combined clinical and MR post-treatment evaluation. No cases of radionecrosis were seen at autopsy. This study shows that MR can demonstrate tumor response to radiation therapy, tumor progression prior to clinical deterioration, post-treatment cyst formation and hemorrhage. Although MR clinical correlation was not optimal on six week post-treatment evaluation, 4-10 month post-treatment MR scanning correlated well with clinical evaluation. MR appears useful in post-therapeutic monitoring of tumor response. PMID- 2234386 TI - Imaging of cerebral arterio-venous malformations by transcranial colour-coded real-time sonography. AB - Transcranial color-coded real-time sonography (TCCS) is a new diagnostic method allowing the non-invasive imaging of parenchymal and vascular structures of the adult brain through the intact skull. A description of the sonographic findings in two patients presenting with a radiologically ascertained arterio-venous malformation is provided. The AVM's can be depicted in the two-dimensional B-mode image as echodense areas interspersed with zones of lower echodensity. Their extension correlated with corresponding MRI images. The color-coded illustration of intravascular flow phenomena allowed the distinct identification of the major afferent feeding vessels, the venous drainage and of the vascular convolution of both AVM's. Information on hemodynamics, as e.g. the blood supply of the angioma by the contralateral internal carotid artery, are obtained by color-coded identification of intravascular flow direction including analysis of the Doppler frequency spectrum. All findings obtained by TCCS complied with those established by angiography. We conclude, that TCCS is a suitable method for early diagnosis and long term follow up of cerebral AVM's. PMID- 2234387 TI - Cerebral blood flow mapping using stable xenon-enhanced CT in sickle cell cerebrovascular disease. AB - The cerebral blood flow (CBF) of 25 patients with sickle cell cerebrovascular disease (SCCVD) was examined using a Xenon-CT flow mapping method. Brain CT and MR findings were correlated with those of the Xenon-CT flow studies. CBF defects on Xenon-CT correlated reasonably well with the areas of cortical infarctions on the MR images, but in 27% of the cases, flow defects were slightly larger than the areas of infarctions on the MR images. In deep watershed or basal ganglia infarctions, abnormal CBF was noted about the cerebral cortex near infarctions in 72% of the patients, regardless of infarction sizes on the MR images. However, decreased CBF was recognized in 4 of the 9 children whose MR images were virtually normal. Thus, the extent of flow depletion cannot be predicted accurately by MR imaging alone. Xenon-CT flow mapping proved a safe and reliable procedure for evaluation of the CBF of patients with SCCVD. Although this study is preliminary, it may have a potential in selecting patients for hypertransfusion therapy, as a noninvasive test and for following children with SCCVD during their therapy. Careful correlation of results of CBF with those of MR imaging or of CT is important for objective interpretations of flow mapping images. PMID- 2234389 TI - Volumetric quantification of brain volume in children using sequential CT scans. AB - We devised a three dimensional method for the accurate measurement of brain volume and applied it to 32 neurologically normal children, 7 children with only mental retardation and 15 children with both mental retardation and motor disturbance. In the group of neurologically normal children, the total brain volume increased from 723 cm3 to 1407 cm3 in order of age. The correlation ratio between the total brain volume and age was significant (P less than 0.0001). The values of the total brain volume and the developmental curve were similar to those of the total brain weight of normal children previously reported. The combined volume of the cerebellum, the midbrain, the pons and the medulla also increased from 76 cm3 to 200 cm3 in a manner similar to that of the total brain. The correlation between total brain volume and head circumference was significant (P less than 0.0001). In the group of children with mental retardation, the total brain volume was relatively smaller than that of neurologically normal children. In the group of the children with mental retardation and motor disturbance, 10 out of 15 cases showed values below -2 SD of those of neurologically normal children. The values of the total brain volume were each less than -3 SD in 3 cases whose head circumferences were each more than -3 SD. Our method for the direct measurement of brain volume based on serial CT scans may be useful for the accurate examination of brain development. PMID- 2234388 TI - Selective cerebral intraarterial DSA. Complication rate and control of risk factors. AB - In 1095 patients 2770 brain supplying arteries have been studied by i.a.-DSA. Definitive neurological deficits occurred in 0.09%, transient deficits were observed in 0.45%. The reduced complication rate in comparison to former studies seems to be a continued effect of technical progress (DSA) and the use of new isoosmotic contrast media. In order to reduce the "training hospital effect" as to complication rate careful supervision of trainees is necessary. The average fluoroscopy time per vessel is proposed as an objective measure of the investigational skill of a neuroradiologist. PMID- 2234390 TI - Use of a new mixture for embolization of intracranial vascular malformations. Preliminary experimental experience. AB - The internal carotid artery system in swine has a special anatomic configuration similar to a brain "arterial-arterial malformation." The internal carotid artery breaks up into a multitude of fine channels (rete mirabile) situated at the base of the skull on the side of the hypophysis. This anatomic arterial model was used to analyze acute and chronic angiographic and histological changes after occlusion of the rete mirabile with I) avitene, II) avitene, and 50% ethanol, III) avitene, 30% ethanol and Polyvinyl alcohol, IV) avitene 50% ethanol and Polyvinyl alcohol, V) IBCA and VI) silk. Histopathological changes observed in the rete mirabile six weeks following occlusion demonstrated that a mixture of avitene, 30% ethanol and Polyvinyl alcohol and IBCA produced the best anatomic results. Embolization with avitene, PVA and ethanol induced a more bland histological reaction than the one observed with IBCA. Preliminary clinical experience with this mixture is reassuring in those cases in which the AVM was surgically resected. The partially thrombosed AVM was easily depressed and compressed by the neurosurgeon allowing for satisfactory hemostasis in and around the nidus of the AVM. PMID- 2234391 TI - (D, L) polylactide microspheres as embolic agent. A preliminary study. AB - Owing to their shape, accurately calibrated microspheres appear to be very suitable material for distal embolization. Moreover, the biocompatible (D, L) polyactide (PLA) microspheres possess two other valuable advantages: easy adjustment of their biodegradation rate, and incorporation of chemotherapeutic agents during their production. The authors describe the preparation of these (D, L) PLA microspheres and their clinical applications as a preliminary step to arterial chemoembolization. PMID- 2234392 TI - Neurography using the intramuscular injection of ionic iodine contrast media. AB - Our report presents a new method of neurography. Sciatic nerve and lumbosacral plexuses in frogs have been visualized after the intramuscular injection of water and lipid soluble ionic iodine contrast media (Telebrix 300, Potassium Iodide 30% and Lipiodol Ultra Fluid). The ascendant flow of the iodine ions (anions) has been achieved by establishing the electrical potential difference between the injection site and the proximal part of the sciatic nerve and lumbosacral plexus. The application of DC current ensued immediately after the injection. Several minutes later the proximal segments of tibial and peroneal common nerves, as well as the sciatic nerve in its full length, have been visualized on X-Ray film. Lumbosacral plexuses became radioopaque after 20 plus minutes. PMID- 2234394 TI - Intracavernous aneurysm. Superior demonstration by magnetic resonance angiography. AB - A case of intracavernous aneurysm in a 56-year-old woman is reported. The superiority of MRI and MRA in the diagnosis is shown. PMID- 2234393 TI - MRI demonstration of cortical laminar necrosis and delayed white matter injury in anoxic encephalopathy. AB - We performed serial radiological examinations on a patient with anoxic encephalopathy. In the early term after the anoxic insult, T1-weighted MRI revealed high signal intensity areas distributed laminarly in the cerebral cortex and diffusely in the putamen, which were thought to reflect the cortical necrosis and necrosis in the putamen. Single photon emission computed tomography using I 123 isopropylamphetamine showed persistent hypoperfusion in the arterial watershed zones. T2-weighted MRI performed several months after the anoxic episode revealed diffuse high-intensity lesions in the arterial water-shed zones. These delayed-onset white matter lesions continued to extend over several months. PMID- 2234395 TI - High field MR imaging of the brain in pseudohypoparathyroidism. AB - Two cases of pseudohypoparathyroidism were examined with a superconductive 1.5 T MR imaging system. High signal intensities were seen in both putamina, pulvinars and dentate nuclei on T1-weighted images. PMID- 2234396 TI - MRI of radiation induced spinal cord glioma. AB - Radiation induced neoplasms of the spinal cord are rare lesions. This report details the MR evaluation of a patient with radiation induced astrocytoma of the cervical cord. The diagnosis of second primary neoplasm should be considered in patients with prior radiation therapy when MRI demonstrates an intramedullary lesion. PMID- 2234397 TI - Amyloidosis of the spine in a patient on long-term hemodialysis. AB - A 54-year-old man with a history of renal failure treated with hemodialysis for over 10 years presented with clinical signs and symptoms and plain radiographic, computed tomographic and magnetic resonance imaging features of cervical vertebral osteomyelitis with spinal cord compression. Decompressive surgery revealed amyloid deposition. In the setting of chronic hemodialysis, differentiation between amyloid deposition and osteomyelitis may not be possible on an imaging basis necessitating biopsy for diagnosis. PMID- 2234398 TI - Spiculated vertebral metastases from prostatic carcinoma. Report of first two cases. AB - Periosteal reaction with spicule formation is very rare in metastatic bone disease, as only 75 cases are reported in the literature. Although prostatic cancer often metastasizes to the spine, spiculation here has not been reported. We present the first two cases of vertebral metastases from prostatic carcinoma with spicule formation giving rise to osseous spinal stenosis and neurological deficits, best demonstrated by CT. PMID- 2234399 TI - MR demonstration of a unilateral olivary hypertrophy caused by pontine tegmental hematoma. AB - Two patients with unilateral olivary hypertrophy (OH) following a pontine tegmental hematoma are presented. Both showed palatal myoclonus and one patient showed an extremity myorhythmia on the opposite side of OH. The magnetic resonance (MR) examination demonstrated an abnormal unilateral hyperintense lesion in the ventral part of medulla oblongata on T2-weighted images. The MR findings were highly suggestive of the pathological nature of the lesion, showing the value of MR. PMID- 2234400 TI - Brown tumor in secondary hyperparathyroidism, causing progressive paraplegia. PMID- 2234401 TI - Bilateral aberrant jugular bulbs. PMID- 2234403 TI - Submicromolar concentrations of zinc irreversibly reduce a calcium-dependent potassium current in rat hippocampal neurons in vitro. AB - The action of the endogenous divalent cation zinc on Ca2+ and Ca2(+)-dependent currents was studied in rat hippocampal CA1 and CA3 neurons in vitro, by means of a single electrode voltage clamp technique. Bath application of zinc (0.5-1 microM) produced a small membrane depolarization associated with an increase in synaptic noise and cell excitability and a depression of the afterhyperpolarization following a train of action potentials. The effects on the afterhyperpolarization, could not be reversed on washout. In voltage-clamped neurons, zinc induced a steady inward current and reduced, at resting membrane potential, the peak amplitude of the outward current underlying the afterhyperpolarization, IAHP. In caesium loaded neurons (in the presence of tetrodotoxin and tetraethylammonium), zinc reduced the slow inactivating Ca2+ current activated from a holding potential of -40 mV. Similar results were observed with nickel and cobalt at comparable concentrations, with Zn2+ greater than Ni2+ greater than Co2+, in their order of potency. In contrast to nickel and cobalt the effects of zinc did not reverse on washout. These results suggest that low concentrations of zinc enhance cell excitability by reducing IAHP. In addition, zinc reduces the slow inactivating voltage-dependent Ca2+ current. The irreversible effect of this metal ion is compatible with a toxic, intracellular site of action. PMID- 2234402 TI - Systemic administration of MK-801 protects against N-methyl-D-aspartate- and quisqualate-mediated neurotoxicity in perinatal rats. AB - MK-801, a non-competitive antagonist of N-methyl-D-aspartate-type glutamate receptors, was tested for its ability to antagonize excitotoxic actions of N methyl-D-aspartate or quisqualic acid injected into the brains of seven-day-old rats. Stereotaxic injection of N-methyl-D-aspartate (25 nmol/0.5 microliters) or quisqualic acid (100 nmol/1.0 microliter) into the corpus striatum under ether anesthesia consistently produced severe unilateral neuronal necrosis in the basal ganglia, dorsal hippocampus and overlying neocortex. The distribution of the damage corresponded to the topography of glutamate receptors in the vulnerable regions demonstrated by previous autoradiographic studies. N-Methyl-D-aspartate produced severe, confluent neuronal destruction while quisqualic acid typically caused more selective neuronal necrosis. Intraperitoneal administration of MK-801 (0.1-1.0 mg/kg) 30 min before N-methyl-D-aspartate injection had a prominent dose dependent neuroprotective effects as assessed morphometrically by comparison of bilateral striatal, hippocampal and cerebral hemisphere cross-sectional areas five days later. A 1 mg/kg dose of MK-801 given as pre-treatment completely protected the infant brain. The same dose of MK-801 was also completely protective when administered 30 or 40 min after N-methyl-D-aspartate and afforded partial protection when given 2 h later. MK-801 pre-treatment also prevented the electrically confirmed behavioral seizures induced by N-methyl-D-aspartate. The drug significantly reduced striatal but not hippocampal or neocortical injury when given as two doses (1 mg/kg) 30 min prior to and immediately following quisqualic acid injection. The data indicate that systemic administration of MK 801 can prevent N-methyl-D-aspartate-induced neuronal injury in perinatal rat brain even when administered after the initial insult. MK-801 also partially antagonized quisqualic acid-mediated neurotoxicity, suggesting that quisqualic acid-induced toxicity is, in part, mediated through N-methyl-D-aspartate receptor activation. The sensitivity of the developing brain to the toxicity of N-methyl-D aspartate provides a sensitive and reproducible in vivo model for exploring these issues and for screening prospective neuroprotective drugs that act at the N methyl-D-aspartate receptor-channel complex. PMID- 2234404 TI - Serotonin attenuates a slow inhibitory postsynaptic potential in rat hippocampal neurons. AB - Activity of hippocampal neurons was recorded in an in vitro slice preparation. Topical application of serotonin produced hyperpolarization, blockade of a slow afterhyperpolarization which follows a burst discharge and blockade of a slow inhibitory postsynaptic potential. The slow inhibitory postsynaptic potential evoked by stimulation of the apical dendritic region of the hippocampus is more sensitive to serotonin than the membrane potential or conductance. The effects of serotonin on the inhibitory postsynaptic potentials are blocked by the 5-HT1a antagonist spiperone, and not by mianserin, a 5-HT2 antagonist. The attenuation of the inhibitory postsynaptic potentials is not accompanied by a change in postsynaptic reactivity to GABA or baclofen. Serotonin blocks repetitive large inhibitory postsynaptic potentials evoked in hippocampal neurons by topical application of 4-aminopyridine. Putative interneurons are more sensitive to topical application of serotonin than pyramidal neurons. Fenfluramine, a serotonin releaser mimics the effects of topical application of serotonin indicating that synaptically released serotonin can produce the changes in membrane potential and reactivity to afferent stimulation. It is suggested that serotonin attenuates slow inhibitory postsynaptic potentials by inhibiting feed forward inhibitory interneurons which impinge upon the recorded pyramidal neurons. PMID- 2234405 TI - Characterization of dopamine release in the rat medial prefrontal cortex as assessed by in vivo microdialysis: comparison to the striatum. AB - Using the technique of perfusion microdialysis combined with a small-bore liquid chromatography system we have measured the basal and drug-induced fluxes of extracellular dopamine in the medial prefrontal cortex of chloral hydrate anesthetized rats and have compared our findings in the cortex to that observed in the striatum. The results were as follows. (1) At a flow rate of 2 microliter/min, the basal level of dopamine in the medial prefrontal cortex was 0.28 +/- 0.1 (n = 32) fmol/microliter perfusate, which was nearly an order of magnitude less than that obtained from the striatum. (2) alpha-Methyl-para tyrosine (150 mg/kg i.v.) significantly decreased the extracellular levels of striatal and cortical dopamine. The magnitude and duration of the responses were similar in both regions. (3) Local perfusion with 30 mM K+ had a more profound effect on dopamine release in the striatum than in the medial prefrontal cortex. The K(+)-induced release in both regions was significantly attenuated in the absence of Ca2+. (4) The anxiogenic beta carboline FG 7142 (15 mg/kg, i.p.) enhanced the release of cortical dopamine by about 50% while it was without an effect in the striatum. (5) Amphetamine (1 mg/kg, i.v.) significantly elevated, while reserpine (5 mg/kg, i.p.) rapidly attenuated, the dopamine level in the medial prefrontal cortex. These studies demonstrate that perfusion microdialysis, in conjunction with small-bore liquid chromatography with electrochemical detection, can be used to measure the basal release of dopamine in the rat medial prefrontal cortex and that the dopamine release process in this region, as has been shown in the striatum, is sensitive to stimulation conditions and pharmacological manipulations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234406 TI - Nerve growth factor in the primate central nervous system: regional distribution and ontogeny. AB - An enzyme immunoassay for nerve growth factor was developed to determine the regional distribution and ontogenic change in the macaque (Macaca fascicularis) CNS. The standard curve of mouse nerve growth factor paralleled the dilution curves of extracts from the primate CNS at the adult and pre-natal stages. Furthermore, the nerve growth factor immunoreactive material comigrated with mouse nerve growth factor by means of carboxy methyl cellulose chromatography. These findings suggest that the immunoreactive material extracted from the primate CNS is mouse nerve growth factor-like molecules. At the adult stage, the highest level of nerve growth factor was in the hippocampus, with relatively high levels also in the hypothalamus, the cerebral cortex, the amygdala, the basal nucleus of Meynert, the septal nucleus, the cerebellum and the caudate nucleus. No detectable amounts were observed in the spinal cord, the substantia nigra or the dentate nucleus. In addition to the CNS, the pituitary gland contained about four times the level found in the hippocampus. At embryonic day 120, a high level of nerve growth factor already existed in the occipital cortex (80% of the level at the adult stage) and in the hippocampus (70% of the level at the adult stage). Between embryonic day 120 and the newborn stage in the occipital cortex and between embryonic day 120 and postnatal day 60 in the hippocampus, nerve growth factor levels increased about 1.7-fold, and after that, they gradually decreased until the adult stage was reached. In contrast, in the cerebellum, the level was quite high during the pre-natal period and declined to one-third at postnatal day 60. The developmental changes in nerve growth factor and choline acetyltransferase activity in the hippocampus were well correlated (r = 0.963) between embryonic day 120 and postnatal day 60. Our studies reveal that nerve growth factor is present in the primate CNS. The high level of nerve growth factor during embryonic stages and the good correlation with choline acetyltransferase activity suggest a physiological role for nerve growth factor in the development of the primate CNS. PMID- 2234408 TI - Calcitonin gene-related peptide in primary afferent neurons of rat: co-existence with fluoride-resistant acid phosphatase and depletion by neonatal capsaicin. AB - Immunohistochemical and histochemical techniques were used to re-examine the extent to which neonatal capsaicin treatment depletes calcitonin gene-related peptide in the dorsal horn of the spinal cord, to determine the localization of calcitonin gene-related peptide in relation to that of fluoride-resistant acid phosphatase in lumbar dorsal root ganglia, and to compare the distribution of these primary afferent markers in the dorsal horn. A substantial depletion of calcitonin gene-related peptide was observed in the dorsal horn of adult rats treated neonatally with capsaicin suggesting that a large proportion of this peptide in the dorsal horn is contained within capsaicin-sensitive primary afferent fibers. In dorsal root ganglia 30% of all or 44% of small- and medium sized calcitonin gene-related peptide-immunoreactive cells were positive for fluoride-resistant acid phosphatase. Conversely, 50% of cells positive for the phosphatase enzyme also displayed immunoreactivity for the peptide. In lamina II of the dorsal horn calcitonin gene-related peptide and fluoride-resistant acid phosphatase were found to have an overlapping distribution. The presence of fluoride-resistant acid phosphatase in a substantial proportion of neuropeptide containing primary sensory neurons suggests a lack of segregation of sensory neuronal populations into peptide- and non-peptide-containing subgroups at least on the basis of non-peptide neurons defined as those containing fluoride resistant acid phosphatase. PMID- 2234409 TI - Neural mechanisms underlying the action of primer pheromones in mice. AB - Our electrophysiological experiments in female mice have provided evidence that electrical stimulation of the accessory olfactory bulb orthodromically excites a subpopulation of tuberoinfundibular arcuate neurons by way of the amygdala. The present study shows that half of such neurons are identified as dopaminergic by examining the effectiveness of infusing 6-hydroxydopamine and 5,7 dihydroxytryptamine locally into the median eminence in blocking their antidromic response. Further attention is focused on excitatory amino acid receptors within the amygdala and the amygdaloid pathway that mediate the accessory bulb-induced excitation of tuberoinfundibular arcuate neurons. The excitatory transmission was reversibly blocked by intra-amygdala infusion (3 nmol) of the excitatory amino acid antagonists kynurenic acid, D,L-2-amino-5-phosphonovalerate, gamma-D glutamylaminomethylsulphonate and D,L-2-amino-4-phosphonobutyrate. Intra-amygdala infusions (3 nmol) of N-methyl-D-aspartate and kainate markedly enhanced the firing activity of tuberoinfundibular arcuate neurons with excitatory inputs from the accessory bulb, whereas similar infusions of quisqualate were without effect Intra-stria terminalis infusions of the local anaesthetic lignocaine completely abolished the excitatory transmission in all the cells tested. Furthermore, tuberoinfundibular arcuate neurons stimulated from the accessory bulb were also orthodromically stimulated from the stria terminalis with a shorter latency. These studies demonstrate that the projections of the accessory olfactory bulb activate excitatory amino acid receptors within the amygdala and subsequently the stria terminalis route, thereby causing excitation of tuberoinfundibular dopaminergic arcuate neurons. This functional pathway can account for the reproductive effects so far described as a consequence of vomeronasal chemoreception. PMID- 2234407 TI - Early accumulation of serotonin in rat spinal cord subjected to traumatic injury. Relation to edema and blood flow changes. AB - Changes in the concentration of serotonin (5-hydroxytryptamine) in the early period after a focal traumatic injury to rat spinal cord were determined and related to the formation of edema and alterations in blood flow. A unilateral, 5 mm-long and 3-mm-deep traumatic injury located 2 mm from the midline was created in the T10-11 segment of the cord. Five hours after the injury the serotonin concentration in the traumatized segment had increased more than 100% compared with controls. There was also a progressive increase in water content of the traumatized segment measured 1-5 h after the injury. On the other hand, the spinal cord blood flow showed a progressive decrease to about 35% of its initial value at 5 h. Pretreatment with p-chlorophenylalanine, a serotonin synthesis inhibitor, impeded the elevation in water content measured 5 h after the trauma. The spinal cord blood flow remained close to normal values and the increase in serotonin was absent. Our results show that trauma to the rat spinal cord will induce changes in the serotonin concentration of the tissue and that the associated formation of edema and blood flow alterations can be alleviated in serotonin depleted rats. Obviously, serotonin plays a significant role in the pathophysiology of traumatic injury of rat spinal cord. PMID- 2234410 TI - Reflex responses of fusimotoneurons to sinusoidal muscle stretching. AB - Reflex response of fusimotoneurons to sinusoidal muscle stretching were investigated in decerebrated cats. Nerve impulses of single fusimotoneurons were recorded from thin filaments dissected from otherwise intact nerves to triceps surae muscles. Amplitude of the sinusoidal stretching of these muscles was 3 mm peak-to-peak and the frequencies 0.1-10 Hz. Electric muscle activity was also recorded in some experiments. Fusimotor responses were similar to those of the skeletomotoneurons in that both were advanced in phase with respect to muscle length changes, while their amplitude increased with increase in stretching frequency. Modulation at the frequency corresponding to the second harmonic of the input signal was predominant in fusimotor responses. It is supposed to appear mainly due to the convergence to fusimotoneurons of afferent impulses from different muscle receptors arriving after different delays. Its functional role is discussed. PMID- 2234411 TI - Synaptic efficacy of inhibitory synapses and repetitive firing in the reinnervating trigeminal and hypoglossal motoneurons. AB - The synaptic efficacy and repetitive firing in masseteric motoneurons after the self-union operation and in tongue protruder motoneurons after their cut axons were reunited to tongue retractor muscles, the styloglossus muscle, were studied in cats. To ensure the correct identification of reinnervating motoneurons, the muscle response produce by an induced spike in a motoneuron by intracellularly injected depolarizing current was recorded. In both masseteric and tongue protruder motoneurons there were no differences on the patterns of postsynaptic potentials produced in reinnervating and non-reinnervating motoneurons by peripheral nerve stimulation, suggesting that the recovery of the synaptic efficacy of inhibitory synapses is time-dependent rather than muscle reinnervation. However, the present study demonstrated that the recovery of processes that control rhythmical firing of motoneurons is probably dependent on muscle reinnervation. PMID- 2234412 TI - Involvement of a cholinergic mechanism in the sustained depolarization and contraction of the lower oesophageal sphincter muscle cells in the cat. AB - Membrane potentials were recorded in vitro with intracellular electrodes from the circular muscle cells of the cat lower oesophageal sphincter and oesophageal body. In addition, the tension of lower oesophageal sphincter and oesophageal body strips was recorded isotonically. Under the experimental conditions, no spontaneous electrical activity or variation in the tension of the strips occurred. The resting membrane potential of the circular muscle cells was significantly lower in the lower oesophageal sphincter (-51.0 +/- 0.3 mV) than in the circular muscle cells of the oesophageal body (-57.1 +/- 0.4 mV). These values were not affected by infusion of tetrodotoxin 3.1 x 10(-6) M. In the presence of atropine (3.5 x 10(-7) M), the resting membrane potential of the circular muscle cells of the lower oesophageal sphincter increased significantly (-57.6 +/- 0.4 mV), whereas the resting membrane potential of the circular muscle cells of the oesophageal body was not significantly affected (-57.8 +/- 0.6 mV). In the presence of atropine, no significant difference in the values of the resting membrane potential of the circular muscle cells was observed between the lower oesophageal sphincter and the oesophageal body. Hyoscine (2.9 x 10(-7) M) significantly increased the resting membrane potential of the circular muscle cells of the lower oesophageal sphincter, whereas eserine (3.6 x 10(-6) M) significantly decreased it. Atropine induced a significant decrease in the membrane resistance of the circular muscle cells of the lower oesophageal sphincter. Atropine decreased the resting tension of lower oesophageal sphincter strips whereas eserine increased it, but no such effects were recorded on oesophageal body strips.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234413 TI - Electrophysiological properties of subpopulations of rat dorsal root ganglion neurons in vitro. AB - Intracellular recordings were made from rat dorsal root ganglion neurons in vitro. Action potentials with an inflection on the falling phase occurred in all cells conducting up to 5.2 m/s and in a proportion of faster conducting cells which decreased with increasing conduction velocity, until no cells conducting faster than 31 m/s had an inflection. Overall, all C-cells (less than 1.3 m/s), 61% of A delta-cells (1.3-12 m/s) and 23% of A alpha/beta-cells (greater than 12 m/s) had inflections. A-cells with inflections were found to be electrophysiologically distinct from those without as they differed in the mean and distribution of every action potential and afterhyperpolarization parameter measured. C-cells differed from all A-cell groups, but the means and distributions of most parameters were closer to those of A-cells with inflections than of A-cells without. In addition, all A- and C-cell action potentials with inflections were tetrodotoxin resistant, while all those without were sensitive. The only parameters whose means differed between A alpha/beta- and A delta neurons were ones which correlated with conduction velocity (action potential duration, overshoot and maximum rate of rise and fall). The response pattern to prolonged current injection did not correlate with conduction velocity, but slightly more A-cells with inflections were single firing. A-cells with long afterhyperpolarizations always fired singly, while those with shorter durations fired singly or multiply. Somatic following frequency was most strongly limited by long afterhyperpolarization duration; it was also slightly lower in A delta- than in A alpha/beta-cells, and lower in A-cells with inflections than in those without. Fibre following frequencies were highest in the fastest conduction neurons. PMID- 2234414 TI - Selective uptake of C-fragment of tetanus toxin by sympathetic preganglionic nerve terminals. AB - Immunohistochemical techniques have shown that the C-fragment of tetanus toxin injected into medial gastrocnemius muscle in the guinea-pig and rat, in addition to its retrograde transport in the axons of the somatomotor, sympathetic and sensory neurons supplying this muscle, is taken up and concentrated by terminal varicosities within pre- and paravertebral sympathetic ganglia at all thoracolumbar levels. Staining was absent in chronically denervated ganglia, demonstrating the specific association of the antigen with preganglionic varicosities. Preganglionic varicosities at all levels were also labelled after C fragment injection into the peritoneal cavity or into denervated medial gastrocnemius; both of these procedures failed to label somatomotor or sensory neurons. Although retrograde trans-synaptic transport could be demonstrated, sympathetic labelling was sparse and non-specific, so that the C-fragment of tetanus toxin is unsuitable for the identification of sympathetic pathways. The selective and widespread uptake of tetanus toxin by sympathetic preganglionic terminals could explain the diverse autonomic symptoms observed in tetanus intoxication. PMID- 2234415 TI - Neural control of ectopic filiform spines in adult tongue. AB - The tongue surface directly above a fungiform taste bud is flat, thinly keratinized, and free of filiform spines. We examined fungiform papillae in serial sections of rat and gerbil tongues after unilateral transection of the chorda-lingual nerve had caused many fungiform taste buds to degenerate. Such empty fungiform papillae often formed a solitary keratinized outgrowth that closely resembled the spine of an ordinary filiform papilla. By six months an ectopic spine was found on 61% of empty fungiform papillae, but never on fungiform papillae that contained a taste bud. Experimental innervation of the tongue reduced the incidence of ectopic filiform spines in proportion to the cross-sectional area of the trigeminal nerve branches tested (the mylohyoid nerve, the lingual nerve, lingual + mylohyoid or lingual + auriculotemporal nerves). The chorda tympani nerve was 60 times more effective than trigeminal nerves in preventing ectopic filiform spines. We suggest that positive and negative trophic actions are normal characteristics of taste axons, for they promote the formation of taste buds and prevent the expression of ectopic filiform spines. By preventing the outgrowth of ectopic spines on fungiform papillae, taste axons maintain a thinly keratinized apical surface that can be breached by the taste receptor cells. PMID- 2234416 TI - Cajal-Retzius cell ontogenesis and death in mouse brain visualized with horseradish peroxidase and electron microscopy. AB - The ontogenetic development of Cajal-Retzius cells was studied in mouse by local application of horseradish peroxidase over the developing neocortex, revelation with 3,3'-diaminobenzidene and examination from horizontal thick sections. Cajal Retzius cells were completely stained in Golgi-like fashion. The Cajal-Retzius cells were seen to be elongated spindle-shaped bipolar neurons with their main processes horizontally oriented. They were exclusively located in the first cortical layer and were connected to the cortex surface by the numerous vertical appendages. Except for these appendages, the Cajal-Retzius cells were two dimensional, with an immature structure at their tips resembling a growth cone. Cajal-Retzius cell dendrites were up to 400-microns-long and reached their maximal length prenatally. Their axon and its collaterals were very fine and sometimes measured several millimetres. It followed a random but planar trajectory confined to the first layer. Healthy Cajal-Retzius bearing growth cones were seen until one week after birth when signs of Cajal-Retzius cell degeneration began to occur and intensified in the days that followed. Rough endoplasmic reticulum and Golgi complex swelling along with a progressive darkening of the Cajal-Retzius cells were revealed by electron microscopy, strongly suggesting that most Cajal-Retzius cells disappear from the first cortical layer. Usually neuronal death is the result of cell deafferentation following synapse retraction; however, this effect does not seem to apply to Cajal-Retzius cells engaged in the process of death since normal synaptic junctions were seen on them. No signs of the morphological transformation of Cajal-Retzius cells into persisting horizontal first layer cells were observed. The concept of dual origin of neocortex is discussed in light of the similar fate of Cajal-Retzius cells and subplate neurons which both are transient neurons. PMID- 2234417 TI - Assessment: generic substitution for antiepileptic medication. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. PMID- 2234418 TI - Assessment: intraoperative neurophysiology. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. AB - Experience to date in both humans and controlled animal research studies substantiates that several electrophysiology tests and monitoring techniques are safe and efficacious, to a variable degree, as commonly applied in the operating room for the following procedures: EEG or SEP to monitor for cerebral ischemia; ECoG and SEP sensory cortex identification to define the limits of cortical resection; SEP spinal cord monitoring; BAEP and cranial nerve EMG monitoring during posterior fossa procedures; functional localization of cortex with direct cortical stimulation in expert hands; and EMG and compound muscle and nerve action potential measurements of various peripheral nervous system structures. All these techniques need to be applied by a well-trained, knowledgeable physician-neurophysiologist or personnel directly under his or her supervision. Clinical situations need to be chosen carefully, avoiding those in which the nervous system is only at low risk. PMID- 2234419 TI - Generic substitutions for antiepileptic drugs. PMID- 2234421 TI - The mesoneocortical dopamine neuron system. PMID- 2234420 TI - How acute brain failure becomes chronic: a view of the mechanisms of dementia related to stroke. PMID- 2234422 TI - Aspiration in bilateral stroke patients. AB - Seventy patients with bilateral strokes underwent neurologic and videofluoroscopic barium swallowing examinations; 34 (48.6%) aspirated. Patients with aspiration were more likely to have posterior circulation strokes, abnormal cough, abnormal gag, and dysphonia. However, patients likely to aspirate can be identified best by the presence of an abnormal voluntary cough, an abnormal gag reflex, or both. The prediction of patients at risk for aspiration was not improved by additional clinical information (ie, presence of dysphonia or bilateral neurologic signs). PMID- 2234423 TI - Prolonged confusion following convulsions due to generalized nonconvulsive status epilepticus. AB - Among patients with a prolonged confusional state after convulsive seizure, we diagnosed 8 cases as generalized nonconvulsive status epilepticus. Six had a history of seizures, and 2 had new onset. The convulsive seizures were generalized in 6 and focal in two. The postictal confusion lasted up to 36 hours in the most prolonged case, and a delayed response to anticonvulsant medications occurred in all cases. The clinical symptoms ranged from mild confusion to coma. Psychiatric manifestations or automatisms were rare. The presumed etiology was due to diverse causes, but a withdrawal state was the most common. EEG demonstrated continuous or nearly continuous generalized ictal discharges of variable morphology. These cases call attention to the fact that some prolonged confusional states following convulsive seizures are in fact due to persistent seizure activity that can be diagnosed by EEG. PMID- 2234424 TI - Verbal memory impairment correlates with hippocampal pyramidal cell density. AB - Thirty-five patients with medically refractory epilepsy localized to the temporal lobe (18 left, 17 right) completed the verbal Selective Reminding Test before surgery. Verbal memory impairments existed before surgery regardless of the lateralization of the seizure focus, but patients with left temporal seizure foci were significantly more impaired. After surgical removal of the mesial temporal lobe structures, 2 blinded observers established volumetric cell densities for hippocampal subfields CA1, CA2, CA3, the hilar area, and the granule cell layer of the area dentata. Statistically significant correlations existed between presurgical memory impairment and cell counts (in CA3 and the hilar area, only) for patients with left temporal seizure foci. These findings support the hippocampal model of memory and complement prior research documenting the memory impairments present after surgical removal of the mesial temporal structures. PMID- 2234425 TI - The opposite pupil in herniation. AB - I serially examined the pupil opposite the one already enlarged from transtentorial herniation in 13 patients. The main abnormalities, stereotyped in most patients, were an initially diminished light reaction with a 2.5- to 4-mm diameter pupil, followed by slight reduction in size, and then reenlargement to greater than original size, all with preserved roundness. Subsequent deterioration varied among patients, but a transitional oval shape was infrequent and oculomotor function was preserved until both pupils were enlarged and fixed. Once the pupil on the side of a mass enlarges, heralding herniation, subsequent deterioration can be appreciated through changes in reactivity and size of the opposite pupil. PMID- 2234426 TI - Spatiotemporal contrast sensitivity differs in normal aging and Parkinson's disease. AB - We measured contrast sensitivity for static and laterally drifting vertical gratings in 12 young adults, 7 normal elderly adults, and 8 patients with Parkinson's disease (PD). We compared static and motion contrast sensitivity for spatial frequencies of 0.25, 1, and 4 cycles per degree (cpd), and temporal frequencies of 1, 3, and 9 Hz. Results show that normal aging leads to a reduction of motion sensitivity for the spatial frequency of 0.25 cpd. Compared with elderly controls, PD patients do not present specific abnormalities in this domain. However, for spatial frequencies of 1 and 4 cpd and temporal frequencies of 1 and 3 Hz, motion sensitivity is worse than static sensitivity in PD patients and not in elderly controls. These findings suggest a specific deficit of motion perception in PD, and possible dopaminergic involvement in the control of visuospatial behavior. PMID- 2234427 TI - Central neurogenic hyperventilation: pharmacologic intervention with morphine sulfate and correlative analysis of respiratory, sleep, and ocular motor dysfunction. AB - Central neurogenic hyperventilation (CNH), for which there is no effective therapy, can eventually result in respiratory fatigue and death. This report describes a patient with CNH due to a brainstem anaplastic astrocytoma who also exhibited disturbances of sleep and ocular motor function. The CNH responded clinically to morphine sulfate and methadone. Analysis of ventilatory response to CO2 before and after morphine demonstrated a depression of ventilatory response (49 to 53% of baseline) and occlusion pressure response (35 to 50% of baseline) to CO2, with a requirement for high doses of naloxone (10 mg IV) to reverse the effect. Polysomnography revealed sustained hyperventilation, elevated O2 saturation, and low end-tidal CO2 throughout all stages of non-rapid eye movement (NREM) sleep, and absence of rapid eye movement (REM) sleep. Ocular motor evaluation disclosed absence of horizontal and reflexive saccades with compensatory head thrusts. Correlation of the clinical and physiologic data with the MRI abnormalities suggested that the lesion responsible for CNH in this patient might reside in the medial tegmental parapontine reticular formation. Since recurrent episodes of hyperventilation responded in a sustained fashion to IV and oral opiates, this treatment may warrant consideration in other patients with CNH. PMID- 2234428 TI - Memory-related neural systems in Alzheimer's disease: an anatomic study. AB - In the primate brain, there are strong connections among the entorhinal cortex, the hippocampal formation, and the amygdala, 3 structures of the ventromedial temporal lobe that are related to memory function. Because memory impairment is a central feature of Alzheimer's disease, we examined the probable cells of origin and terminal zones of these connections in the brains of humans affected by the disease, using thioflavine S, Alz-50, and anti-A4 amyloid protein immunocytochemistry. Specific cytoarchitectural areas and lamina that give rise to projections from the entorhinal cortex, the hippocampal formation, and the amygdala consistently contained neurofibrillary tangles. The terminal zones of many of these projections contained neuritic plaques, Alz-50-positive neuritic alterations, and A4 deposition. Other cytoarchitectural areas and lamina, sometimes immediately adjacent, were consistently spared from these Alzheimer changes. This pattern of Alzheimer-related alterations would disrupt projections among the entorhinal cortex, hippocampal formation, and amygdala at multiple sites, and also disrupt projections between these structures and cortical and subcortical targets. In functional terms, this pattern of structural damage is likely to be as devastating as bilateral destruction of the ventromedial temporal lobe, and thus contribute substantially to the memory disorder seen in this condition. PMID- 2234429 TI - Hemiparkinsonism-hemiatrophy syndrome: clinical and neuroradiologic features. AB - We evaluated 11 patients with hemiparkinson-hemiatrophy syndrome, 6 with body and contralateral cerebral hemispheric hemiatrophy, 4 with only body hemiatrophy, and 1 with just brain hemiatrophy. The mean age of symptom onset was 38.1 years (range, 18 to 54) with 5.2 +/- 3.1 (mean +/- SD) years of illness until the last follow-up visit. The presenting symptom was unilateral tremor in 6 patients, hand dystonia in 2, bradykinesia in 2, and abnormal gait in 1 patient. Three patients had a good response to levodopa, 4 had moderate response, and 2 patients had a poor response. During a mean follow-up period of 1.7 years (range, 4 months to 5 years), the Hoehn and Yahr score changed in only 3 patients: 2 gained 1.5 points and 1 gained 3 points over 2.5 years. We discuss the association between hemiparkinsonism-body hemiatrophy and contralateral hemispheric hemiatrophy, and raise the possibility of early childhood brain insult with delayed-onset parkinsonism. PMID- 2234430 TI - Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6. AB - We identified the cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF), and interleukin-6 (IL-6) by specific radioimmunoassays in the CSF of patients with multiple sclerosis (MS) and other neurologic diseases (OND). There was a high incidence of detectable IL-1 beta in patients with active MS compared with inactive MS or OND patients. TNF was also more frequently present in active MS than in OND CSF. By contrast, most MS CSF did not contain detectable IL-6. There was no correlation between the degree of CSF pleocytosis and the level of individual cytokines, suggesting that cytokine accumulations may be derived from CNS, and not CSF, cells. As IL-1 beta and TNF experimentally induce astrogliosis, demyelination, temperature elevation, lassitude, and sleep, and results raise the possibility that these cytokines may contribute to a variety of manifestations in MS and in other disease states. PMID- 2234431 TI - Anti-GM1 IgM antibodies in motor neuron disease and neuropathy. AB - We found anti-GM1 IgM antibodies in 23% of 56 patients with motor neuron disease (MND), in 19% of 69 patients with neuropathy, and in 7% of 107 controls with other neurologic and nonneurologic diseases. Most of these patients had anti-GM1 IgM antibody titers of 1:80 or less; slightly higher antibody titers (up to 1:640) were found in 3 patients, 1 with MND and 2 with neuropathy, and very high titers (1:20,480) in a patient with MND and an IgM kappa M protein that reacted with GM1, GD1b, and asialo GM1. Six other patients with anti-GM1 IgM that also bound to GD1b. Reactivity with GD1b did not correlate with anti-GM1 titers but was only present in patients with MND or neuropathy. Anti-GM1 IgM antibodies may be a normal constituent of the human antibody repertoire but their frequency and, in some cases, their levels are higher in patients with MND and neuropathy. The origin and the pathogenetic role of these antibodies in neural impairment remain to be established. PMID- 2234432 TI - Cervical magnetic stimulation. AB - We stimulated the cervical region with a 9-cm-diameter magnetic coil on centered on the spinous processes in 21 normal subjects. We obtained maximal amplitudes with clockwise coil current in right-sided upper extremity muscles and counterclockwise coil current in left-sided upper extremity muscles. Optimal stimulation sites for biceps, triceps, and abductor digiti minimi were C-3 or C 4, C-4 or C-5, and C-4, C-5, or C-6, respectively. The latencies of the muscle responses varied little in the same subject in spite of marked amplitude changes due to suboptimal position of the coil or submaximal stimulator output. In abductor digiti minimi, the amplitude of the muscle response on cervical magnetic stimulation was 9 to 100% of the supramaximal amplitude on wrist electrical stimulation. We established normal values for latency, amplitude, and interside differences for the above 3 upper extremity muscles. The findings were reproducible, and the latencies obtained with large coils from different manufacturers in the same subjects were comparable. We found no advantage in bipolar recording over tendon-belly montage. Comparison of magnetic and electrical needle root stimulation in the same subjects showed that the magnetic stimulus was more proximal in biceps and triceps, and that the site of excitation was approximately the same in abductor digiti minimi. Indirect assessment of the longitudinal site of excitation based on F-wave minimal latency indicated that excitation occurred within millimeters of the emergence of axon of the peripheral motor neuron. PMID- 2234433 TI - Neuronal injury due to HIV-1 envelope protein is blocked by anti-gp120 antibodies but not by anti-CD4 antibodies. AB - Picomolar concentrations of native or recombinant coat protein gp120, from the human immunodeficiency virus type 1 (HIV-1), injured rat retinal ganglion cell neurons in culture. This form of neurotoxicity could be completely abrogated by anti-gp120 but not by control preimmune serum, suggesting that the lethal effects of the purified preparations of the envelope protein were due to gp120 and not to a contaminant. Entry of HIV-1 is mediated by gp120 binding to a surface protein, designated "CD4," which is located, for example, on T lymphocytes. However, in the present study, specific anti-CD4 antibodies, at concentrations known to block effects mediated by high-affinity binding to CD4 on the surface of rat T cells, did not prevent neuronal injury induced by gp120. These findings suggest that injury of central neurons engendered by gp120 may be responsible, at least in part, for the neurologic manifestations observed in as many as 2/3 of the patients with acquired immunodeficiency syndrome, such as dementia, myelopathy, and visual loss, even in the absence of superinfection. In contrast with previous studies, however, this report suggests that the deleterious effects of gp120 on neurons may not be mediated via binding to the CD4 molecule. PMID- 2234435 TI - Antibodies to synthetic peptide (125-148) of the alpha-subunit of human nicotinic acetylcholine receptor in sera from patients with myasthenia gravis. AB - We measured the amount of antibodies to a synthetic peptide that corresponds to the alpha-subunit residues Lys125-Thr148 of human acetylcholine receptor (AChR) in myasthenic sera. We detected anti-peptide antibodies in 52% (89/171) of the patients with myasthenia gravis (MG), but none in any of the healthy controls. Anti-peptide antibodies should provide a valuable immunologic parameter for the clinical evaluation of MG, but no apparent correlation was observed between the titers of anti-peptide and anti-AChR antibodies. PMID- 2234434 TI - Kearns-Sayre syndrome presenting as renal tubular acidosis. AB - Renal tubular acidosis and tetany were the 1st manifestations of Kearns-Sayre syndrome in a 5-year-old child. Subsequently, he developed progressive external ophthalmoplegia, ptosis, retinopathy, heart block, and endocrinopathy. There was a 7.5-kb deletion of mitochondrial DNA documented in muscle, kidney, skin fibroblasts, and leukocytes, providing evidence for a multisystem mitochondrial cytopathy. PMID- 2234436 TI - Electron transfer flavoprotein: ubiquinone oxidoreductase (ETF:QO) deficiency in an adult. AB - A 19-year-old woman with mild myopathic symptoms from age 6 and fasting intolerance presented with a Reye-like syndrome and a myopathy. Investigations disclosed a lipid storage myopathy, type II glutaric acidemia, and carnitine deficiency in skeletal muscle. Riboflavin and carnitine treatment corrected the metabolic abnormalities and she improved clinically. She later died from pulmonary complications secondary to aspiration. Subsequent studies established electron transfer flavoprotein: ubiquinone oxidoreductase (ETF:QO) deficiency (fibroblast ETF:QO activity was 2.9 mU/mg, normal range is 14.1 +/- 3.8 mU/mg) as the cause of her illness. This is the first documented case of ETF:QO diagnosed in an adult. PMID- 2234437 TI - Streptococcus bovis meningitis: report of 2 cases. AB - We describe 2 cases of Streptococcus bovis meningitis and review the 9 cases previously reported. This microorganism is a rare cause of meningitis in which there are no distinctive clinical or laboratory features. The Gram stain of the CSF is usually negative. Ten of the 11 cases had some underlying disease or comorbid condition that predisposed to S bovis infection: gastrointestinal disorder, endocarditis, CSF leak, polymyalgia rheumatica, and mandibular block. Treatment with high-dose penicillin is usually adequate. PMID- 2234438 TI - Cavernous hemangioma of the spinal cord: report of 2 unusual cases. AB - We present 2 cases of spinal cord intramedullary cavernous hemangioma; 1 patient is the 1st reported case of multiple spinal cord lesions. Diagnosis is greatly enhanced by the use of MRI. PMID- 2234439 TI - Eosinophilia-myalgia syndrome (L-tryptophan-associated neuromyopathy). AB - Histopathologic study of skeletal muscle biopsy in a patient with eosinophilia myalgia syndrome following L-tryptophan use showed prominent lymphocytic perineuritis, neuritis, and perimysial fasciitis. The presence of perineuritis and neuritis provides a histopathologic basis for clinical features of neuropathy in eosinophilia-myalgia syndrome and occurred in conjunction with a fasciitis or interstitial myositis that was predominantly perimysial and focally endomysial. PMID- 2234440 TI - Neuroleptic malignant syndrome: a unique association with a tricyclic antidepressant. AB - We report the lst case of neuroleptic malignant syndrome occurring in a patient receiving desipramine, a tricyclic antidepressant, with no exposure to neuroleptics. Our case suggests that this syndrome may be caused by a central imbalance between norepinephrine and dopamine, and not by dopamine depletion alone. PMID- 2234441 TI - Selective involvement of the pyramidal tract on magnetic resonance imaging in primary lateral sclerosis. PMID- 2234442 TI - Cerebellar atrophy following acute intoxication with phenytoin. PMID- 2234443 TI - Intracerebral hemorrhage following scorpion bite. PMID- 2234444 TI - Primary CNS lymphoma. PMID- 2234445 TI - Rett's syndrome. PMID- 2234446 TI - Antineuronal antibodies. PMID- 2234447 TI - [The aorto-coronary bypass in the elderly patient]. AB - In the FRG one person every ten is more than 70-years old; the average life expectancy, often underestimated, is about 11 years for the 70-years old and 6 years for 80-years old. The modern approach to coronary disease has broadened the indications for coronary artery bypass grafting in the elderly. The present report, studying 152 patients more than 70-years old, suggests the usefulness of a myocardial revascularization in the elderly; it remains to define the relative contraindications (renal failure, high LVEDP, valve replacement). However, the symptomatic improvement we could achieve (95.45%) seems to be a good result, considering the low CABG-related postoperative lethality (1.9%). The trend of our results regardless of 5 years survival is also encouraging (85.1%). PMID- 2234448 TI - [Hyperkinetic ventricular arrhythmia during the treadmill test in chronic ischemic heart disease]. AB - Aim of this study was to evaluate the pattern of onset and the characteristics of ventricular arrhythmias (VA) observed during treadmill test (TT) in patients with chronic ischemic heart disease (CIHD). Two groups of patients with CIHD were retrospectively compared: group A consisted of 120 consecutive patients with premature ventricular beats (PVBs) either isolated (greater than 2/min) or repetitive during exercise, or maximal exercise, or recovery; group B consisted of 140 consecutive patients without PVBs during TT. The two groups were comparable in mean age, male/female ratio, incidence of previous myocardial infarction, of previous coronary artery by-pass graft or of percutaneous transluminal coronary angioplasty. There were no significant differences between the two groups regarding the parameters evaluated during TT: duration of exercise, maximal heart rate, heart rate-systolic blood pressure product as well as in the percentage of positive tests for acute myocardial ischemia (51.6% vs 40.7%). In the two subgroups of patients who underwent coronary arteriography and left ventricular angiography (24/120 and 23/140 patients respectively) no differences were found in the number and distribution of critical coronary stenosis and of dyskinetic or akinetic areas. In both groups A and B the QTc interval at maximal exercise was significantly longer than its value at rest (p less than 0.001), but there was no relevant difference between the two groups. In group A patients with VA during maximal exercise (n = 60) showed a higher prevalence of complex VA (class Lown greater than or equal to 3) compared to the others (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234449 TI - [Surgical risk in patients with heart valve disease in non-cardiac surgery]. AB - Our purpose was to retrospectively evaluate major risk of non cardiac surgery in patients with valvular heart disease. We studied retrospectively 136 patients, 44 affected by aortic, 81 by mitral and 11 by mitroaortic valve disease. NYHA class was I-II in 130 and III in 6 patients. Sixty four patients underwent orthopedic surgery, 57 patients occulistic surgery and 5 patients urological surgery. There were no hospital deaths. Fifteen patients developed major perioperative complication: 7 serious ventricular arrhythmias, 6 hypotension, 2 "hypertensive attacks". We conclude that non cardiac surgery is safe in patients with valvular heart disease. PMID- 2234450 TI - [The use of dynamic electrocardiographic monitoring in scleroderma patients]. AB - A comparative analysis of arrhythmias by "basal" electrocardiogram (ECG) and by continuous 24-hour Holter electrocardiogram monitoring was performed in 17 patients with systemic sclerosis (16 women and one man). Our study confirms that rhythm disturbances are better detectable using Holter monitoring. In fact, no patients had ventricular arrhythmias detected by ECG; on the contrary, Holter monitoring revealed ventricular arrhythmias in nine patients (53.3%). This method also revealed a ventricular tachycardia, not detected by ECG. In two patients ventricular repolarisation abnormalities without symptoms was revealed. PMID- 2234452 TI - [Peripheral nerve injuries during carotid endarterectomy]. AB - Our experience with patients undergoing carotid endoarteriectomy over a 10 year period has been retrospectively reviewed. Nerve injuries were detected by reviewing postoperative progress and clinical notes. One hundred thirty-four procedures were performed on 120 patients, to 15 of whom (9%) occurred major nerve injuries. These included seven vagal nerve injuries causing ipsilateral vocal cord paralysis and hoarseness, five injuries of the marginal mandibular nerve and three injuries of the hypoglossal nerve. None of the patients with nerve injury had a stroke as a result of carotid operation. Vocal cord paralysis was documented by laryngoscopy. The incidence of cranial nerve injury during carotid endoarteriectomy appears to be higher than expected, particularly if asymptomatic patients are controlled. PMID- 2234451 TI - [A study of the distribution of some risk factors in patients with myocardial infarct. Different cardiovascular prevention methods in relation to age]. AB - In order to evaluate whether a different method of preventive approach to ischemic cardiopathy is appropriate in relation to age, the distribution of some classic cardiovascular risk factors (cigarette smoke, cholesterol) and a stress related risk factor (type of work) was studied in two groups of patients, aged respectively over and under 60, admitted to hospital for acute myocardial infarction. The most significant data were: blood cholesterol values less than 220 mg/ml, found mainly in older patients; a larger number of heavy smokers in the group of patients aged under 60; the majority of patients were employees. In the light of these results, the paper discussed the need for different forms of preventive intervention, both clinical and epidemiological, for Ischemic cardiopathy in relation to age. PMID- 2234453 TI - [Follow-up in femoral artery embolectomy]. AB - The results of 112 femoral embolectomies performed on 100 patients were reviewed. Operative mortality rate was 15% and early amputation (within 30 day-after the procedure) 18%. The role of early amputation was closely related to the time of leg ischemia. Current follow-up as established for 86 patients. 5 years and 10 years survival rates for the group were 49% and 40%. Although early survival is decreased after femoral embolectomy long term survivors can be expected to live independently with excellent limb salvage and function. PMID- 2234454 TI - [Popliteal aneurysm. Our experience in 65 cases]. AB - Fifty patients with 65 popliteal aneurysms underwent reconstructive procedures (mean age 64). Atherosclerosis is almost the exclusive cause of popliteal aneurysms. Most of the cases showed an acute ischemia, while he others were asymptomatic or presented a complication of venous occlusion or neural compression. Numerous cases were found incidentally at amputations (these were not included). The best operational method is ligation of the aneurysm sometimes with partial resection and autologous venous graft bypass. The immediate results were excellent in all cases, loss of limb was observed in only three. PMID- 2234455 TI - [Evaluation of acute cardiotoxicity from the combination cyclophosphamide mitoxantrone-5-fluorouracil (CMF) with Holter ECG]. AB - By making use of a twenty-four hour Holter monitoring, it as been possible to compute the acute cardiotoxicity of the cyclophosphamide + mitoxantrone + 5 fluorouracil (CNF) association in twenty oncologic patients (pts) each of whom being immune from organic cardiopathy emerging clinically and at their first cycle of chemotherapy. The following parameters have been computed: meaningful changes in the heart frequency; premature atrial and ventricular depolarizations, both as a first appearance and as a clear growth in the number; the ST dislocation entity; malignant ventricular arrhythmias. The administration of CNF at the doses of: 600 mg/m2 of cyclophosphamide, 12 mg/m2 of mitoxantrone and 600 mg/m2 of 5-fluorouracil , has caused a meaningful increase in the heart frequency on 6 pts (30%), an increase of premature atrial depolarization on 4 pts (20%) with an appearance ex novo on 2 pts (10%), an increase of premature ventricular depolarization, without any passing to superior Lown classes, on 2 pts (10%) with an appearance ex novo on 3 pts (15%). Although the results in the study point out a frequency percentage of simple hyperkinetic arrhythmias equal to the 55%, the lack of more serious hyperkinetic arrhythmias and of intense disorders of ventricular repolarization testified to a synergic effect as a determining factor on the acute cardiotoxicity of the previously discussed association, in our opinion. PMID- 2234456 TI - [Pharmacologic effects and safety profile of bethanechol in the differential diagnosis of pseudo-anginal thoracic pain]. AB - The use of bethanecol has recently been proposed to improve the diagnostic accuracy of esophageal manometry in identifying the origin of symptoms in patients with non cardiac chest pain. In this study we report our experience in 30 patients who underwent esophageal functional studies. Despite its low diagnostic value, bethanecol test (two subsequential doses of 50 micrograms/kg) demonstrated an excellent safety profile, there were few side effects, and patients tolerance was good. The Holter electrocardiographic study showed an isolated case of transient atrioventricular block. PMID- 2234458 TI - [AIDS: Mycoplasma and/or HIV?]. PMID- 2234457 TI - [Dilated cardiomyopathy and visceral anomalies in myotonic dystrophy]. AB - In dystrophia myotonica clinical evidence of cardiac involvement usually appears several years after the onset of neuromuscular symptoms. In more than 90% of cases there is damage to the specialized cardiac tissues and in about 7% of cases there are alterations to the myocardium. We report a case characterized by early and spread deterioration of the pump function developing into refractory congestive heart failure. The contemporary involvement of the smooth muscle of gallbladder and colon confirms the hypothesis that dystrophia myotonica is a pan muscle disease. PMID- 2234459 TI - [Anatomo-functional consequences of the radical surgery of the cervico-cephalic region in oncologic patients]. AB - The role of surgery in head and neck cancer treatment is now well established, as it appears the most effective approach to such patients, while other therapies (i.e. chemotherapy, radiotherapy) can be of some help as second choice procedures. Surgery demonstrates however its own pitfalls, as it can often cause secondary anatomo-functional defects. The main problems appear to be related to the impossibility of physiological feeding following composite resection for oral cancer. An immediate reconstruction by transposition of myocutaneous flaps is of the utmost importance, as it reestablishes the preoperative condition lessening hospitalization time and postoperative disabilities. Neurological lesions, an unfrequent major complication of cervical lymphadenectomy, can cover a wide range of seriousness, from hardly detectable sensorial deficits to the impossibility of spontaneous ventilation. In this paper the Authors, on the basis of their experience, describe the measures to be taken in order to avoid secondary lesions (or to minimize their effects) in head and neck cancer surgery. PMID- 2234460 TI - [Osteo-articular amyloidosis caused by dialysis. Clinical and radiologic aspects]. AB - Twenty-nine patients who had received chronic hemodialysis for more than 5 years provided the material for the present study. In 12 of them (41%) there were radiological findings of dialysis related amyloidosis, mainly destructive spondyloarthropathy of the cervical spine (n = 11) and geodes of the shoulder (n = 5). When compared with negative patients, these patients were significantly older (p less than 0.001 and had been dialyzed for longer periods of time (p less than 0.01). Moreover, in such patients there was an higher incidence of carpal tunnel syndrome (p less than 0.025) and shoulder pain (p less than 0.001). Our results confirm that osteoarticular amyloidosis is a frequent long-term complication of chronic hemodialysis and underline the correlation between clinical and radiological findings. PMID- 2234461 TI - [Behavior of ionized calcium in hypertensive and normotensive patients]. AB - Serum concentrations of ionized calcium have been measured in a group of 38 patients with essential hypertension (26 women and 12 men with mean age 61 +/- 12 years) and in a group of 19 normotensives (14 women and 5 men with mean age 70 +/ 12 years). Serum Ca++ levels were significantly lower in hypertensives than in normotensives (4.16 +/- 0.43 mg/dl and 4.46 +/- 0.38 mg/dl respectively, with p less than 0.05). The lower serum concentrations found in hypertensives may be due ions in arterial smooth muscle cells may cause an increase of vascular tone and peripheral resistances. Our results support, in agreement with other Authors, the possible role of ionized calcium in the pathogenesis of essential hypertension. PMID- 2234462 TI - [Occult blood in the feces for the early diagnosis of tumors of the digestive system]. AB - Mortality from colon-rectal cancer is rising steadily in Italy; of malignant tumours, those of the nitestine come second after those of the lung. Hence the ned for early diagnosis based on the search for occult blood in the stools. This test takes on important significance for screening purposes in subjects at risk. Alongside diagnosis it is important to effect primary prevention diet, food and environmental factors). A negative result of the identification of occult blood in the stools absolutely does not exclude tumour of the intestinal tract. A positive finding, on the other hand, does not necessarily confirm the presence of a tumour. Such an investigation was carried out at the Analysis Laboratory of the Sant'Antonio di Ovada Hospital, Health Unit 74, in the period between October '87 and June '88. The samples were taken from hospitalised patients and from out patients. The samples from hospitalised patients totalled 324 and 20 proved positive for occult blood; of the out-patient samples (176), positivity was observed in 12. Hospitalised patients were recontrolled and results were confirmed positive. The out-patients did not present for further controls. PMID- 2234463 TI - [Plasma beta-endorphin and caffeine consumption in chronic hemicrania]. AB - Thanks to recent biochemical and neuroendocrine findings, migraine belonging to the group of primary headaches appears as a pathology of the antinociceptive system with evolutive character. It has been demonstrated, in fact, that right at the early stage of migraine, there is a significant reduction in liquoral concentrations of beta-endorphin (beta-E), endogenous opioid peptide followed by a similar change in the plasma opioid system. The opioid system deficiency is even more evident after stimulation tests that point to reduced reactivity of the hypothalamo-hypophyseal system with respect to stimuli that in normal subjects trigger hypophyseal beta-E incretion. Caffeine, a member of the methyl-xanthine group, is an interesting molecule in the study of migraine patients because the chronic intake of this substance, contained in numerous analgesics, has been related to the chronic nature of the pain. The purpose of the present study is to assess the relationship between caffeine consumption and plasma opioid system. With the administration of a single oral dose of caffeine, normal subjects present an increase in plasma concentrations of beta-E, while in patients with chronic migraine, the response is significantly lower. These data confirm the poor reactivity of the plasma opioid system to pharmacological stimuli in migraine. Average daily consumption of caffeine has also been determined. It was not possible to establish a correlation between consumption of caffeine and plasma concentrations of beta-E whether basal or after stimulus with caffeine. PMID- 2234464 TI - [Cardiac effects of prostacyclin infusion]. AB - The purpose of this investigation is the evaluation of cardiac effects of short term prostacyclin intravenous infusion. Prostaglandin I2 has been administered at rate of 5 ng/kg/min. Systolic blood pressure (mmHg) remains unchanged, heart rate (beats/min) significantly increases (p less than 0.01). Diastolic blood pressure (mmHg) significantly decreases (p less than 0.01) during the first hour: this decrease is not significant during the second and third hour. The QTc shortens during the first and third hour and returns to normal values during 60-90 minutes of infusion. This preliminary study suggests that cardiac effects of prostacyclin infusion are indirect. PMID- 2234465 TI - [Clinical experience with piperacillin in the prophylaxis of post-operative infections]. AB - Ninety patients who had undergone surgery have been treated with piperacillin as a prophylaxis for hospital infections. Twenty-two (24.4%) emergency operations and sixty-eight (75.6%) elective ones have been performed. Thirty-five open drainages, seven vacuum drainages and fifty-five urinary catheters have been placed. Post-operative infections occurred in 18 patients (20%), five of them submitted to emergency operations and thirteen submitted to elective operations. In eight cases an open drainage had been placed and in three cases a vacuum rate. The Author concludes that the hospital infections rate agrees with that occurring in the quoted sources; that open drainages, especially if placed through surgical wound, have main responsibilities for infections, and that piperacillin acted as a very well tolerated antibiotic and a highly manageable and effective one, offering therefore a good prophylaxis for hospital infections. PMID- 2234466 TI - [Netilmicin in a single daily dose for treatment of systemic infections]. AB - The Authors report the results obtained in 35 patients of either sex suffering from various systemic infections and treated with netilmicin. Netilmicin has been intramuscularly administered in once daily dose of 4.5 mg/kg (mean daily dose 294.3 mg) for a mean duration of 17.8 days. The clinical resolution of the infections has been achieved in 97.1% (34 patients) of the study population; only one patient showed failure. Thirty-three of the 35 baseline causative pathogens have been eradicated. The local and systemic tolerability was good. The serum pharmacokinetics showed bactericidal levels of netilmicin and no serum accumulation. PMID- 2234467 TI - [Socioeconomic status and survival in multiple myeloma]. AB - In order to investigate the relationship between socioeconomic status and survival in multiple myeloma, a group of 121 patients, followed from first diagnosis to their demise, was subdivided into three social classes: high, medium, and low. Social class subdivision was performed taking into account the degree of education, occupation, and income. Significant differences (p less than 0.05) exist regarding mean survivals, survival curves, clinical stages, and responses to therapy between the three considered classes. A low socioeconomic status is associated with shorter survival, higher frequence in poor clinical stage, and less percentage of positive responses to chemotherapy. In conclusion, the socioeconomic status is an important prognostic factor in patients with multiple myeloma, to be considered with other clinical and laboratory data. PMID- 2234468 TI - [Anatomo-clinical considerations on early gastric cancer]. AB - The morphological features of early gastric carcinoma and its differences with respect to advanced gastric cancer are discussed on the basis of reported data. In particular, prognostic morphological implications and therapeutic possibilities are discussed. Study of recurrences suggest factors to improve prognostic productivity. PMID- 2234469 TI - [Scientific institutions for treatment and care: purpose, characteristics and specific role in the oncologic sector]. AB - The qualities of Comprehensive Health Care Institutes facilities established to foster, carry out and coordinate activities of scientific research and assistance in the field of biomedicine are described. At present there are 23 centers, their activity being based on two fundamental features: 1) topical research in specific themes characterizing the role these Institutes continuously play; 2) specialized research concerning subjects of particular interest and/or urgency suggested by the Ministry of Health. PMID- 2234470 TI - [Peculiar clinical pictures of Guillain-Barre-Strohl syndrome. Description of 2 clinical cases]. AB - A clinical of 37 patients suffering form Guillain-Bare syndrome has been carried out. Because of their unusual onset and clinical course, two of the cases are reported in full. The first case presented atypical onset modalities characterised by dysarthria, dysphonia and dysphagia with subsequent diplegia of the facial nerve and motor involvement of all four extremities; the second was difficult to diagnose and over time it turned out to be disimmune chronic recurrent polyneuropathy. The clinic instrumental diagnostic and therapeutic course of this case, which was characterised by the poor response to corticosteroid therapy as a result of which use of immunosuppressor (azatioprine) and plasma-feresis were employed with a reaosable improvement, is described in detail. The differential diagnosis and nosologica classification are discussed. PMID- 2234471 TI - [Unilateral cavernous angioma of the thalamus disclosed by transitional disorders in the upward gaze]. AB - We describe a case of a cavernous angioma of the right thalamus, identified by MRI, showing transient vertical diplopia in the upward gaze, present only in protracted recumbency. We consider possible pathogenetic mechanisms in an attempt to explain this peculiar disturbances. In addition we emphasize that MRI is the most sensitive procedure for detection of the cavernous angioma. PMID- 2234472 TI - [Eosinophilic gastritis. Clinico-pathologic considerations on a case and review of the literature]. AB - The clinical, radiographic and histological features of a case of eosinophilic gastritis in a 26 year old-man without personal or familial signs of allergy are reported. The Authors pointed out the importance of radiographic and histological aspects of the case studied. Therefore they represent essential methods for a correct diagnosis and an appropriate management that in this case is only pharmacological. The diagnosis of eosinophilic gastritis is, however, important for the recognition of specific allergens. PMID- 2234473 TI - [Myocardial damage and pheochromocytoma. Description of 2 cases and review of the literature]. AB - The usual presentation of phaeochromocytoma is well known. It is a catecholamine producing tumor of the sympathochromaffin system that typically cause sustained hypertension or hypertensive crisis. Rarely it has an uncommon clinical presentation with or without arterial hypertension and so the most significant symptoms are episodes of left ventricular failure, arrhythmias, ischemic ECG changes, angina pectoris, myocardial infarction, hypertrophic or dilated cardiomyopathy. On report two cases of uncommon presentation of phaeochromocytoma and a few cases of myocardial damage from the literature are reviewed. PMID- 2234474 TI - [Serum paraprotein in a patient with chronic lymphatic leukemia]. AB - We report a case of chronic lymphocytic leukemia associated with paraproteinemia which proved to be a complete immunoglobulin IgM lambda. This case is reported because the process of cellular differentiation exposed to intrinsic or extrinsic stimulation may undergo morphofunctional variations which lead to the formation of plasma cells with extremely high secretionary capacities during the course of chronic lymphocytic leukemia. PMID- 2234475 TI - [Andersson's phenomenon in HLA-B27 negative ankylosing spondylitis]. AB - A computed tomography (CT) and conventional radiography study is reported in a case of HLA-B27 negative ankylosing spondylitis. The value of CT in comparison with conventional radiography in evaluation of anatomic alterations is determined. PMID- 2234476 TI - [Cardiovascular involvement and relative risk factors in systemic sclerosis. Personal contribution]. AB - In systemic sclerosis (SS), cardiovascular commitment was recorded in an autopsy series, in widely different percentages, from 12 to 81%. On the other hand, clinical diagnosis of cardiopathy is made in far fewer cases. In addition, the coexistence of renal and/or pulmonary commitment makes difficult separation between primary and secondary heart damage. In 22 patients (2 m, 20 f) aged between 34 and 75 (average 55 +/- 11) with SS, a study has been made of the a) prevalence of cardiovascular commitment; b) the significance of the classic risk factors; c) the erythrocyte filtration time or TF (index of microangiopathic damage). Metabolic stability, fibrinogen, haematocrit and TF (Reid et al. method) were assessed in each patient. Nine patients (40.9%) presented ischaemic cardiopathy (myocardial infarction in three and effort angina in six), one (4.5%) presented hypertensive cardiopathy. Conduction disturbances were observed in five patients (22.7%). Whereas a statistically significant increase in TF was observed in cardiopaths, no differences in plasma levels of glucose, cholesterol or fibrinogen were observed. The incidence of smoking and the familial factor were also insignificant. PMID- 2234477 TI - [Regulation mechanisms in prolactin secretion. Possible role of the hypophyseal renin-angiotensin system]. AB - Recent studies have shown a possible role of different factors in the regulation of prolactin secretion. In fact many neurotransmitters (dopamine) and peptides can modulate prolactin release from anterior pituitary lactotrophs. In vitro and in vivo studies, Angiotensin II has been shown to increase prolactin release. On the basis of these data we have studied the effects of enalapril (ACE-Inhibitor) on baseline plasma prolactin in nine hypertensive post-menopausal women. The results indicate that 15-day inhibition of angiotensin-converting enzyme by enalapril significantly reduced serum prolactin levels. These data suggest that the Angiotensin II may play a role in the control of prolactin secretion in hypertensive women. PMID- 2234478 TI - [Hyponatremia in cirrhosis with ascites]. AB - Hyponatremia complicates ascitic hepatic cirrhosis with frequency and gravity related to the gravity of the cirrhosis itself. When hyponatremia develops, it worsens the already present secondary hyperaldosteronism and makes therapy with spironolactone inefficacious. From a pathophysiologic viewpoint a pathogenetic role in determining hyponatremia is attributable to the reduced plasmatic renal perfusion; in several patients a syndrome of inappropriate ADH secretion develops. Other neurohormonal systems (catecholamines, prostaglandins, natriuretic hormones) are probably very important in modifying renal hemodynamics and renal tubular function. In some patients a causative role for hyponatremia is attributable to iatrogenic factors (e.g.: diuretics). From a therapeutic viewpoint, we examine some schedules, pharmacologic or not, that, however, are far from being useful for all patients. We discuss, mainly, water restriction, osmotic diuretics with or without loop diuretics, loop diuretics followed by sodium reintegration and concentration-reinfusion of ascites or application of peritoneovenous shunt. PMID- 2234479 TI - [Chronic gastritis. A study of 151 cases diagnosed using gastric biopsy]. AB - With the aim to detect a correlation between endoscopic aspects and histological features of chronic gastritis, the Authors have analysed retrospectively a series of 151 cases where endoscopic alterations were likely due to chronic gastritis and in all cases multiple biopsies were performed. A possible correlation between endoscopy, histology and occurrence of intestinal metaplasia has been carefully evaluated. Only in chronic atrophic gastritis a certain relationship between endoscopic features and histologic diagnosis was detectable: in the same cases a high incidence of intestinal metaplasia was found as well, independently from the severity of endoscopic and/or histologic aspects. The Authors discuss the controversial problems in terminology and endoscopic definition of chronic gastritis. PMID- 2234480 TI - [Campylobacter pylori infection. Results of an investigation of 130 patients]. AB - After recalling the main data on diagnosis, pathogenesis and treatment of CP infection, the results of a study on 130 patients are presented. PMID- 2234481 TI - [Echocardiographic analysis of the left ventricular mass in smokers]. AB - A morphometric echocardiographic analysis of left ventricular mass was performed in 110 heavy smokers and 110 controls aged 20-60. Taken as a whole, the smoker group revealed a higher ventricular mass index (88.4 +/- 19.5 v 78.3 +/- 16.8 g/sq m; p less than 0.01). The difference was not significant in the 20-40 age group (78.1 +/- 18.3 v 76.7 +/- 18.1 g/sq m) but was highly significant (p less than 0.001) in the 41-60 age group (96.0 +/- 18.8 v 80.7 +/- 15.8 g/sq m). The increase in mass may be related to increased catecholamine incretion, raised blood viscosity due to increased fibrinogen and haemocrite and to transitory but repeated increases in telesystolic stress caused by the cigarette smoke. The increase in myocardial mass together with other well-known coronary alterations induced by smoking might explain the greater incidence an severity of ischaemic heart disease, not to mention sudden death among heavy smokers. PMID- 2234482 TI - [Epidemiologic observations on the subject of phlebopathy of the legs and its dermatologic complications]. AB - The authors carried out an epidemiological study on a group of 10032 patients with chronic venous insufficiency, composed of 2686 males (26.77%) and 7346 females (73.23%). The case report is divided into varicose diseases (83.30%) and sequelae of deep vein thrombosis (16.70%). As well as the relationship between sex and age is considered rate of dermatological complications, with regard both to the type of venous diseases (65.54% varicose and 34.46% post-thrombotic) and to their clinical manifestations. As well as any family connection, various environmental factors are taken into account such as the patient's work, noxae iatrogenic, pregnancy and obesity. PMID- 2234483 TI - [The use of weight and height data reported in surveys for screening for obesity and juvenile arterial hypertension]. AB - The surveying of weight and height allows to measure for every subject the body mass index which is a risk indicator both for obesity and for juvenile blood hypertension. The A. have verified and demonstrated that the surveying of weight and height orally told by teen-agers can be a rapid and economic instrument to execute a first screening for such pathologies. PMID- 2234484 TI - [Study of a population sample conducted using the bioenergy gold test]. AB - Experiments carried out using the bioenergy gold test showed that a bioradiant subject working on water without touching, is able to modify the evolution of the gold colloid generated by chemical reaction in the treated water sample. To complete these researches, experiments were carried out on 50 pranotherapeutic practitioners and on 50 normal subjects. Statistical analysis shows that the results in normal subjects differ from those in the pranotherapeutic practitioners. These observations confirm that pranotherapeutists act physically on the water, modifying the structure of the liquid and the chemical gold test is able to reveal these changes. PMID- 2234485 TI - [A systematic approach to the prediction of psychosomatic disease]. AB - This paper is an introduction to the "philosophy" adopted in research on the influence of mental factors in the onset of psychosomatic diseases. The research is oriented to the construction and implementation on a computer of a model that makes it possible to formulate predictions regarding the onset and possibly the classification of the "type" of psychosomatic disease so as to be able to activate an appropriate prophylaxis. PMID- 2234486 TI - [Additional contribution to the epidemiology of fractures of the proximal end of the femur in the elderly (1965-1985)]. AB - The seasonal incidence of hip fractures was studied in the Department of Orthopaedics of the University of Siena in a 22 year period (1965-1985). The fracture incidence rate per 100,000 individuals in the population at risk was calculated. The incidence rate of fracture increased significantly in women during the period studied, whereas there was no significant increase in men. PMID- 2234487 TI - [Survey on goiter in elementary school children in the Bisagno and Trebbia valleys (Liguro-Emilian Apennines)]. AB - The authors have made an inquiry about school-children of two villages of Northern Appennines: Bargagli and Ottone, formerly seats of endemic goiter. The disappearance of endemic goiter in the younger generations of these villages, is in accordance with previous observations by one of the writers suggesting that sheep represent an important ecologic factor in endemic areas. PMID- 2234488 TI - [Role of the cerebral CAT examination in the diagnosis of neurotoxoplasmosis]. AB - A case of central nervous system toxoplasmosis is reported. Attention is called to the diagnosis of this infection; moreover, the authors emphasize the importance of the TAC brain for the diagnosis and evaluation of the clinical evolution and response to the therapy. PMID- 2234489 TI - [Clonidine abstinence syndrome. A clinical case]. AB - During hospitalization a patient with acute pulmonary oedema caused by myocardial dilation and chronic kidney failure presented high blood pressure and repeated episodes of supraventricular tachycardia. The complication was attributed to the withdrawal of clonidine and was treated by reintroduction of the drug combined with nifedipine, nitroderivates and antiarrhythmic drugs. PMID- 2234490 TI - [Hereditary spherocytosis and splenectomy]. AB - The case of a sixteen year old girl with hereditary spherocytosis, submitted to splenectomy, is presented. After operation the patient had four serious infections; for this reason she is now treated by antibiotic prophylaxis. PMID- 2234491 TI - [AIDS in Italy: update to March 31, 1990]. PMID- 2234492 TI - Immunohistochemical evidence for the presence of protein kinase C beta-subtype in rat motoneurons and myoneural junctions. AB - The localization of protein kinase C beta-subtype-like immunoreactivity (PKC-beta LI) was studied in the spinal cord and in different striated muscles of rat. In the spinal cord, large motoneurons in the ventral horn were PKC-beta immunoreactive (IR). Strong immunoreactivity to PKC-beta was found in large nerve bundles between muscles, and in smaller nerves among muscle fibers. Myoneural junctions, which showed weaker immunoreactivity to PKC-beta, were also demonstrated in all muscles studied; the external ocular muscles, the diaphragma and the triceps surae muscle. Muscle cells were not labelled. PMID- 2234493 TI - Differential control of operant and consummatory licking in rats. AB - The failure of rats to optimize their behavior when drinking from two retractable spouts available for single licks was analyzed. The rats were trained in an apparatus where the contacted spout was withdrawn after completion of a lick and the other spout was presented. After 5 days of such forced spout alternation training the animals continued to emit 2.7 instead of the optimum 1.0 lick per spout presentation (LPSP). With water available in one spout only the average LPSP at the empty spout dropped to 1.2 and increased to 3.6 at the water containing spout. It is argued that the operant licks at the dry spout approach the ideal value of 1.0 LPSP whereas the number of LPSPs at the water spout is increased by the consummatory nature of licking triggered by the presence of water in the oral cavity. PMID- 2234494 TI - Changes in calcitonin gene-related peptide immunoreactivity in the rat dorsal horn following electrical stimulation of the sciatic nerve. AB - Immunoreactive staining for calcitonin gene-related peptide (CGRP) in the rat superficial dorsal horn (L4-L5 segments) was examined following electrical stimulation of the sciatic nerve. Electrical stimulation for twenty minutes at an intensity to elicit both A and C fiber volleys resulted in a significant decrease in CGRP immunoreactivity in the medial two-thirds of the dorsal horn on the stimulated side as compared to the non-stimulated side of the spinal cord. The change was most pronounced in the medial area of the dorsal horn, with a 54% decrease in immunostaining density compared to the non-stimulated side. In contrast, when the sciatic nerve was stimulated for the same period at an intensity that stimulates only A fibers, there was no significant difference in the density of immunoreactive staining in the dorsal horn between the non stimulated and stimulated sides of the spinal cord. These results suggest that activity in a specific population of primary afferent fibers causes a dramatic depletion of CGRP in the dorsal horn. PMID- 2234495 TI - Progressive loss of messenger RNA and delayed neuronal death following transient cerebral ischemia in gerbils. AB - We examined mRNA, cytoplasmic RNA and structural damage in the hippocampus of the gerbil brain after transient ischemia by in situ hybridization, Acridine orange histochemistry and immunohistochemistry. Progressive decline of mRNA became visible in the CA1 region after reperfusion for 3 h and loss of cytoplasmic RNA and emergence of structural damage in 3 days. Reduction of mRNA in the CA3-CA4 region was transient. The findings suggested positive correlation between progressive loss of mRNA and delayed neuronal death. PMID- 2234496 TI - Influence of the nervous system on experimentally induced urethral inflammation. AB - We have studied the contribution of the nervous system on experimentally induced urethral inflammation in the rat. Urethral inflammation was induced by inserting latex strips into the urethra. The effects of different experimental procedures was assessed by using a 4-graded inflammation scale based on the histological findings. Attenuation of urethral inflammation was produced by administration of capsaicin at birth. A more complete attenuation was produced by sympathectomy prior to application of the latex strip. Urethral inflammation was also severe in the spontaneous hypertensive rat. Injection of morphine into the third ventricle of the brain significantly reduced the experimentally induced urethral inflammation. These data taken together indicate that the sensory and postganglionic innervation of the urethral mucosa as well as the central nervous system is critically involved in the inflammatory reaction of the urethra following exposure to latex strips. PMID- 2234497 TI - The regional difference of neuronal susceptibility in the dentate gyrus to hypoxia. AB - The effects of hypoxia on neuronal activity in dentate gyrus granule cells were studied in submerged guinea pig hippocampal slices. In all regions of the dentate gyrus granule, the amplitude of the population spike recorded from the dentate granule cell layers, in response to electrical stimulation of the perforant path, decreased during hypoxia and recovered during reoxygenation. However, the ventral dentate gyrus granule cells (upper blade) were more susceptible to hypoxia than the dorsal ones (lower blade), indicating regional differences of neuronal susceptibility to hypoxia in the dentate gyrus. PMID- 2234498 TI - Potassium channel activators abolish excitotoxicity in cultured hippocampal pyramidal neurons. AB - When hippocampal pyramidal neurons are grown in culture they develop excitatory synaptic contacts. If these cultures are perfused with Mg2(+)-free, glycine supplemented medium the neurons exhibit fluctuations in [Ca2+]i and associated cell death ('excitotoxicity'). These phenomena involve the activation of NMDA receptors. When cultures are treated with the K(+)-channel activators cromakalim and diazoxide both the [Ca2+]i fluctuations and the neuronal death are abolished. These effects are reversed by the sulfonylurea glyburide. It thus appears that K(+)-channel activators may be a novel therapeutic intervention in epilepsy and associated disorders. PMID- 2234499 TI - Intradermal injections of bradykinin or histamine cause a flare-like vasodilatation in monkey. Evidence from laser Doppler studies. AB - The spreading cutaneous vasodilatation (flare) that follows a cutaneous injury is readily visible in humans but cannot be visualized in monkey. To determine if monkeys exhibit this neurally mediated reaction, cutaneous blood flow changes after intradermal injections of bradykinin and of histamine were monitored in the hairy skin of pentobarbital anesthetized monkeys. Using a laser Doppler device, recordings of cutaneous blood flow were made at distances of 15 and 25 mm from the injection of 50 microliters of saline, bradykinin (10(-3) M) and histamine (10(-3) M). These sites were beyond the radius of the wheal caused by bradykinin (6.3 mm) or histamine (6.8 mm). At both recording sites, both drugs caused an increase in blood flow that was significantly larger than that caused by the injection of the same volume of saline. These results provide evidence that although a flare is not visible in monkey skin, a flare-like vasodilatation does occur over an area of at least 50 mm diameter. PMID- 2234500 TI - Respiratory patterning of the rat olfactory bulb unit activity: nasal versus tracheal breathing. AB - To assess the role of nasal/tracheal (N/T) breathing in the respiratory patterning of the olfactory bulb (OB) neurons, the activity of 21 units was recorded in 6 anesthetized rats set with a cannula enabling reversible tracheotomy: the rats could inhalate either through nasal pathways or through trachea directly. Shift from tracheal to nasal breathing induced respiratory patterning in 7 units. The changes were steady, reversible and reproducible. The present data, matched with previous ones, indicate that tracheotomy and anesthesia decrease the occurrence of respiratory patterning in OB neurons. The experiments also suggest that peripheral as well as central structures may be a source of respiratory modulation in the olfactory bulb. PMID- 2234501 TI - Extracellular tumor necrosis factor induces a decreased K+ conductance in an identified neuron of Aplysia kurodai. AB - Recombinant human tumor necrosis factor (rhTNF) was pressure-applied onto the the soma of identified neuron R12 in the Aplysia abdominal ganglion. rhTNF induced a slow inward current (ITNF, 80-100 s in duration, 5-10 nA in amplitude) associated with a conductance decrease. ITNF begins 1-2 s after applying rhTNF and peaks in 5-6 s. ITNF was decreased by hyperpolarization and had a reversal potential of approximately -87 mV (close to the K+ equilibrium potential). Ion substitution and pharmacological experiments suggest that ITNF is due to a decreased K+ conductance and that TNF, a product of macrophages, may form an important link in communications between nervous and immune systems. PMID- 2234502 TI - Catalepsy induced by carbachol microinjected into the pontine reticular formation of rats. AB - Rats were implanted stereotaxically with permanent guide tubes aimed at the pontine reticular formation. Carbachol was microinjected in the awake, freely moving rats. Catalepsy was evaluated with the horizontal bar test. Intense and long-lasting, dose-dependent catalepsy was observed following microinjections of 2-8 micrograms of carbachol. Pretreatment with intraperitoneally administered scopolamine significantly reduced the cataleptogenic effect of carbachol. These results show that the pontine reticular formation is part of the neuroanatomical substrate of catalepsy induced by cholinergic drugs. PMID- 2234503 TI - The proton-activated inward current of rat sensory neurons includes a calcium component. AB - Many neurons possess a proton-activated conductance, IH, which supports a large transient inward current at negative potentials and thereby depolarizes cells during rapid drops in external pH. The channels underlying this conductance are permeant to monovalent cations, with a clear preference for sodium. In earlier experiments, it appeared that divalent cations were impermeant: increasing concentrations of extracellular Ca2+ actually decreased the current amplitude. Using whole-cell patch clamp recording techniques, we find that the proton activated channel is permeant to Ca2+ ions. In the absence of monovalent cations, a substantial current is supported by divalent cations. The previously reported block results from competition between divalents and monovalents. This finding suggests that IH may provide a pathway for Ca2+ entry during the acidification that accompanies normal synaptic transmission, excessive electrical activity, and tissue ischemia. PMID- 2234505 TI - Tetrahydroaminoacridine increases acetylcholine synthesis and glucose oxidation by mouse brain slices in vitro. AB - 1,2,3,4-Tetrahydro-5-aminoacridine (THA; tacrine) reportedly improves cognitive deficits in certain individuals with Alzheimer's disease. The present study describes increased glucose oxidation and acetylcholine (ACh) synthesis by mouse brain slices after THA treatment. THA increased [U-14C]glucose decarboxylation and ACh formation in a concentration-dependent manner in hippocampal slices (50 nM less than 50 microM less than microM). In striatal and cortical slices, 50 microM THA effectively elevated the oxidation of glucose and its incorporation into ACh. Thus the efficacy of THA treatment on Alzheimer patients may be partially related to increased ACh synthesis and oxidative metabolism. PMID- 2234504 TI - Microinjections of nicotine in the medial pontine reticular formation elicits REM sleep. AB - Microinfusion of non-specific cholinergic muscarinic-nicotinic agonists, such as carbachol, into the medial pontine reticular formation readily elicits REM sleep. It has generally been assumed that muscarinic receptors mediate the action of cholinergic agonists in triggering rapid eye movement (REM) sleep. Very little is known, however, about the role of nicotinic mechanisms in REM sleep generation. In this study, we administered nicotine and Ringer's solution into the medial pontine reticular formation of freely moving cats. Compared to control Ringer's injections, nicotine increased REM sleep and decreased wake and slow wave sleep (SWS) I percentage. Nicotine also shortened the time to REM sleep onset. These findings suggest a role of nicotinic mechanisms in REM sleep generation. PMID- 2234506 TI - Effects of hyperinsulinemia on local cerebral insulin binding and glucose utilization in normoglycemic awake rats. AB - The present study was carried out to characterize the effects of insulin, using the euglycemic hyperinsulinemic clamp, on insulin binding and glucose utilization in specific areas of rat brain, by autoradiographic methods. Binding of [125I]Insulin was significantly higher in the hippocampus CA1, the ventromedial and lateral hypothalamus nuclei of the hyperinsulinemic rats than in control rats. Glucose utilization was slightly but not significantly decreased in the hippocampus CA1, the ventromedial and lateral hypothalamus of hyperinsulinemic rats. These data suggest that insulin, via its specific receptors, may exert its central actions by affecting glucose utilization. PMID- 2234507 TI - Effects of polyvalent cations and dihydropyridine calcium channel blockers on recovery of CNS white matter from anoxia. AB - The effects of anoxic injury on the functional integrity of mammalian central white matter were studied electrophysiologically using the rat optic nerve model. Previous studies on this model have shown that extracellular Ca2+ is critical to the production of irreversible anoxic injury, and suggest that during anoxia Ca2+ crosses the membrane to enter the intracellular compartment. We attempted to elucidate the mechanism by which this damaging Ca2+ influx occurs. The inorganic Ca2+ channel blockers Mn2+ (1 mM), Co2+ (1 mM) or La3+ (0.1 mM) had no effect on recovery of the area under the compound action potential after a standard 60 min period of anoxia; only Mg2+ (10 mM) significantly improved recovery (54.9 +/- 8.9% vs. 28.7 +/- 10.1%, P less than 0.005). Treatment with organic Ca2+ channel blockers of the dihydropyridine class, nifedipine (1-10 microM) or nimodipine (1 40 microM), also had no effect on recovery from anoxia. We conclude that Ca2+ influx during anoxia does not occur via conventional Ca2+ channels sensitive to polyvalent cations or dihydropyridines. PMID- 2234509 TI - Distribution of Alzheimer's disease amyloid A4-generating enzymes in rat brain tissue. AB - To screen for putative amyloid A4-splitting proteinases, model peptide substrates homologous to the N- and C-terminal portions of the A4 protein were synthesized. The N-terminal A4-splitting enzyme activity was found to be higher in the hypothalamus and limbic area, compared with in the cerebral cortex and cerebellum in 2-month-old rat. The activity decreased throughout the brain in 20-month-old rat. On the other hand, the activity of the putative C-terminal A4-splitting enzyme was significantly higher, 1.4-fold, in the hippocampus than in the cerebral cortex in the young rat. The activity also significantly decreased in the brain of 20-month-old rat, but was still higher in the cerebral cortex, hippocampus and cerebellum. PMID- 2234508 TI - Inhibitory influences of mammalian FMRFamide (Phe-Met-Arg-Phe-amide)-related peptides on nociception and morphine- and stress-induced analgesia in mice. AB - The effects of two endogenous mammalian FMRFamide (Phe-Met-Arg-Phe-NH2)-related peptides, an octapeptide F8Fa (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) and an octadecapeptide A18Fa (Ala-Gly-Glu-Gly-Leu-Ser-Ser-Pro-Phe-Trp-Ser-Leu-Ala-Ala Pro-Gln-Arg-Phe -NH2) on morphine- and restraint stress-induced analgesia and basal nociceptive sensitivity, as measured by the latency of a foot-lifting response to a warmed surface, were examined in male mice. Intracerebroventricular (i.c.v.) administrations of F8Fa and A18Fa (0.10-10 micrograms) during the day time significantly reduced morphine (10 mg/kg) and restraint-induced analgesia at 30 min after administration, with F8Fa having a greater inhibitory effect than A18Fa. At night during the dark period i.c.v. F8Fa also significantly reduced the elevated nocturnal thermal response latency, while not affecting the shorter day time nociceptive responses. Peripheral administrations of the prototypic opiate antagonist, naloxone (1.0 mg/kg), had similar inhibitory effects on morphine- and stress-induced analgesia, and the day-night rhythm of nociceptive sensitivity. These results indicate that F8Fa and A18Fa are involved in the modulation of opioid analgesia and suggest that these endogenous FMRFamide-related peptides may be associated with the expression of the day-night rhythm of opioid-mediated nociceptive sensitivity. PMID- 2234510 TI - Cycles of nursing. PMID- 2234511 TI - An interview with Lucille Joel. Interview by Barbara J. Barnum. PMID- 2234512 TI - Inside ICN headquarters with Constance Holleran. Interview by Craig Little. PMID- 2234513 TI - A national health insurance program: a nursing perspective. PMID- 2234514 TI - International credentials review: crucial and complex. PMID- 2234515 TI - Baccalaureate and master's degree programs in nursing accredited by the NLN 1990 91. PMID- 2234516 TI - Standard of care: the honest error of judgment rule. PMID- 2234517 TI - Legal implications of routine screening for asymptomatic silent myocardial ischemia. AB - A recent case in California raises legitimate concern about the risks of a lawsuit arising out of a routine physical examination. This ruling has an ominous portent for many physicians who either are not current or are not comfortable with the available testing procedures for screening asymptomatic patients for silent myocardial ischemia. PMID- 2234518 TI - Carotid endarterectomy under local anesthesia. AB - Carotid endarterectomy has been used increasingly in the management of cerebrovascular disease. However, morbidity and mortality statistics for this procedure have caused criticism. The authors believe neurologic and medical complications can be reduced with the use of regional anesthesia for carotid endarterectomy. PMID- 2234519 TI - Maintaining an office laboratory. AB - The author discusses the need to have a complete, up-to-date procedure manual available at all times; information on ways to investigate reference laboratories is included. PMID- 2234520 TI - Carcinoma of the male breast. AB - Carcinoma of the male breast remains an unusual entity. Because of this, large series of patients are infrequent and a standard of care has not been established. In this study, 31 male patients with mammary carcinoma were treated over a 29-year interval. The course of these individuals was examined and comparisons were made with the existing literature. PMID- 2234521 TI - Squamous cell cancer of the larynx in an intravenous drug user with AIDS. AB - We present the case of a 29-year-old intravenous drug user with AIDS and squamous cell cancer of the larynx. Profound immunosuppression was evident by an OKT4:OKT8 ratio of 0.1. Simultaneous treatment of the laryngeal cancer by laser vaporization and treatment of immunosuppression with zidovudine resulted in no tumor recurrence after one year. PMID- 2234522 TI - Parathyroid adenoma with conflicting parathyroid hormone levels. AB - For discrepant diagnoses in a patient with hypercalcemia, the authors utilized three different parathyroid hormone assays. The new two-site immunoradiometric assay (IRMA) proved to be the most accurate and is recommended in the differential diagnosis of hypercalcemia. PMID- 2234523 TI - Pediatric cancer mortality rates in New Jersey and the United States. AB - The authors studied pediatric mortality rates for four major categories of neoplasms for the years 1950 to 1985. This report indicates differences in trends between the rates of the New Jersey population and of the United States population, for males and females, and whites and nonwhites. PMID- 2234524 TI - Intussusception in childhood. AB - We present our experiences with 41 consecutive cases of intussusception. Most cases had a preliminary barium enema performed that successfully reduced the intussusception in 12 cases. Twenty-nine patients were explored surgically; bowel resection was carried out in 6 patients, and surgical reduction was carried out in 23 cases. PMID- 2234525 TI - Physicians' office laboratories. AB - The number of physicians' office laboratories (POLs) is increasing. Formal technical education and certification for physician office laboratory personnel assure more accurate results. PMID- 2234526 TI - Focal Candida hepatitis in a patient with Richter's syndrome. PMID- 2234527 TI - Contemporary leadership begins with mentoring. PMID- 2234528 TI - Contemporary leadership: mentors and stewards. PMID- 2234530 TI - Modern mentoring: strategies for developing contemporary nursing leadership. PMID- 2234529 TI - Nurse executive profile of excellent nursing leadership. PMID- 2234531 TI - The mentor perspective. PMID- 2234532 TI - The mentee perspective. PMID- 2234533 TI - An interactive model of leadership. PMID- 2234534 TI - Nursing leaders as mentors: how are we doing? PMID- 2234535 TI - The influence of gender on communication for nurse leaders. PMID- 2234536 TI - Toward achievement of mentoring for nurses. PMID- 2234537 TI - The most important characteristics of nursing leaders. PMID- 2234538 TI - Mentoring: a concept analysis. PMID- 2234539 TI - The importance of risk assessment to the nation's health and economy. AB - The global marketplace is changing rapidly. Never in history has the opportunity to capture new markets with new products and new generations of products been greater. However, never has the chance of losing established markets been higher. We are failing to develop new products despite the fact that Americans have paid for the science from which the world's new technologies were developed. There are many reasons for our failure to turn scientific leads into products. One of the most obvious is that we overestimate the risk of new technologies. Present policy uses a conservatively biased risk assessment process to estimate risk. This process uses many assumptions to bridge gaps in our scientific knowledge about risk. If we wish to be competitive, we must bring safe, inexpensive new products to the marketplace faster. We must seek ways of making our policies more effective while still protecting public health. Risk assessment sets the standards for product development, product approval, and environmental release. A slight miscalculation in "safety levels" can result in tens of billions of dollars in cost added to products. These added costs have a major and direct impact on the competitiveness of U.S. products in the global marketplace where differences in consumer acceptance can be calculated in a few percentage points difference in price.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234540 TI - Quantitative approaches to human risk assessment for noncancer health effects. AB - The estimation of risk for health effects due to chemical exposure is important to the development of standards for regulating the manufacture, use and release of chemicals into the environment. The quantitative data used to develop risk estimates usually come from laboratory animal studies employing relatively high dose levels. Thus, both interpolation from high to low dose levels and extrapolation from laboratory animals to humans are required. The approach most widely used for noncancer end points is to determine the no-observed-adverse effect level (NOAEL) for the critical effect and then apply uncertainty factors (UFs) to account for scientific uncertainties in the total data base, such as response variability within and between species, the lack of chronic exposure data, the lack of a NOAEL, etc. The resulting value is a reference dose (RfD), i.e., the dose at or below which there is unlikely to be any excess risk. One difficulty with the NOAEL/UF approach is that it does not provide a basis for estimating risk at doses above the RfD; thus, if the exposure assessment indicates that human exposure is above the RfD, there is no way to judge the risk of that exposure. Alternative quantitative approaches for risk estimation of noncancer end points have been proposed and include both statistical and biologically-based dose-response modeling. Research is currently underway to further develop and explore the application of such approaches. PMID- 2234541 TI - Towards quantitative risk assessment for neurotoxicity. AB - Methods for quantitative risk assessment have been developed in some detail for carcinogens. These methods attempt to be consistent with current knowledge about the mechanism of carcinogenesis and are probably not applicable to neurotoxicity endpoints. The traditional approach for neurotoxicants has been to define the NOAEL (No Observed Adverse Effects Level) or LOAEL (Lowest Observed Adverse Effects Level) and to divide by a safety factor. One of the weaknesses of this approach is that it does not yield a risk estimate; however, this approach has been widely used, and it is consistent with very limited data. Alternative methods to assess risk are available and have been applied to existing data. These methods are very much dependent upon the nature of the data analyzed, but current data are often limited and do not allow good and comprehensive risk assessments of neurotoxic endpoints. Additional experiments and expanded experimental designs can facilitate improved and more precise risk assessments. Experiments should consider dose ranges which encompass conceivable environmental exposures. Experiments should measure and report individual, as well as group response, and indices of exposure. Finally, more work needs to be done to compare responses across several species. More comprehensive experiments can only lead to more comprehensive risk assessments. PMID- 2234542 TI - Analysis of dose/time/response relationships for chronic toxic effects: the case of acrylamide. AB - This case study illustrates how a very simple dynamic modeling approach can extract information of interest for both toxic mechanism research and risk assessment from a series of dose/time/response data. The technique is applicable for effects that are thought to result from damage processes that are reversible, at least at low doses and times of exposure. The data sets analyzed provided information on some specific manifestation of acrylamide neurotoxicity produced by different combinations of acrylamide dose rate and duration of exposure. Assuming that responses occur when a specific amount of axonal damage accumulates, and that the repair of damage depends directly on the amount of damage present, the dose-related change in the time required to produce a specific type of effect can be used to estimate: (1) The rate of repair of the incipient damage - and differences in repair rates for different individuals within species, and among different species, and (2) The dose of acrylamide that would be just barely able to produce each effect in each species, if the experiment were conducted over the animal's entire lifespan. Information of the first type may also be helpful in neurotoxicology research. Specific biomarkers for the main process causing a particular response should be repaired in different locations and in different species with the dynamics that are consistent with the repair rates calculated from the dose vs. time-of-effect data. PMID- 2234543 TI - Neurotoxicology dose/response assessment for several cholinesterase inhibitors: use of uncertainty factors. AB - Dose/response assessment for non-carcinogenic endpoints typically uses the Acceptable Daily Intake (ADI) or Reference Dose (RfD) approach, in which a dose believed to cause no toxic effect is divided by a number of safety or uncertainty factors (e.g., to control for variability and cross-species extrapolation), in order to estimate a dose presumed to have no adverse effects in humans. With the establishment of neurotoxicology testing guidelines, routine use of uncertainty factors to undertake neurotoxicity dose/response assessment procedures is likely. This approach to dose/response assessment has not yet been widely applied to neurotoxicity data. The purpose of this study was to assess the use of uncertainty factors and the assumptions underlying the use of the uncertainty factor method in assessing risk for several known human neurotoxicants. Because of the availability of a large neurotoxicity data base which included human exposure data, parathion, diisopropylfluorophosphate, physostigmine and acrylamide were chosen for this analysis. Literature searches were conducted for both human and animal data. The resulting data were assigned to one of five end point categories: Neurochemistry/neuropathology, physiology/consummatory behavior, sensory/motor, electrophysiology, and learning/memory behavior. No observed-adverse-effect levels (NOAELs) and/or lowest-observed-adverse-effect levels (LOAELs) were determined when possible for each end point and for several species. Reference doses (RfDs) were calculated and compared across species. A number of issues and critical assumptions were identified. PMID- 2234544 TI - Effects of exposure period and nutrition on the developmental neurotoxicity of anticonvulsants in rats: short and long-term effects. AB - The results of three experiments on the functional neuroteratogenicity of anticonvulsants in rats are presented. Two of the experiments have been reported previously and are reviewed here, while the third experiment is presented here for the first time. The first experiment examined prenatal phenytoin (200 mg/kg), trimethadione (250 mg/kg), and phenobarbital (80 mg/kg) for critical period effects by exposing separate groups of rats to the drugs or to vehicle on embryonic (E) days 7-10, 11-14, or 15-18. Phenytoin produced effects in the E11 14 offspring, but few effects in the E15-18 offspring, and almost no effects in the E7-10 offspring. Phenytoin's E11-14 effects in the offspring were increased pivoting, delayed swimming ontogeny, hyperactivity, impaired water maze learning, and impaired passive avoidance retention. The second experiment looked for phenytoin's long-term effects. Phenytoin-exposed offspring administered 200 mg/kg on E7-18 exhibited numerous postnatal dysfunctions, including water maze learning deficits that persisted to beyond 501 days of age. The learning deficits were neither increased nor decreased in severity at this age compared to those seen in littermates tested at 50 days of age. The third experiment assessed the role of manganese in counteracting phenytoin-induced postnatal dysfunction and the possible confounding effects of maternal undernutrition associated with the drug's administration. The typical pattern of phenytoin-induced behavioral effects was observed in rat offspring. The results demonstrated that undernutrition was not a confound, since pair-feeding and pair-watering controls did not diminish the phenytoin-induced dysfunction in the offspring. Also, administration of a manganese supplementation (200 ppm in the drinking water) during gestation did not significantly alter the pattern of phenytoin-induced postnatal effects. PMID- 2234545 TI - Risk assessment of the developmental neurotoxicity of lead. AB - Lead has long been recognized as a developmental neurotoxicant. Although no reasonable doubt exists about this qualitative characterization, quantitative aspects of the developmental neurotoxicity of lead have been more difficult to resolve. This paper focuses on two key issues in a risk assessment of lead: the blood lead level of concern, i.e., the lowest level of exposure associated with neurotoxic effects in children, and the magnitude and implications of such effects. The distinction between a threshold and a level of concern is also discussed, along with the issue of whether a threshold exists for lead-induced health effects. PMID- 2234546 TI - Polypeptide growth factors in mammalian development: some issues for neurotoxicology and behavioral teratology. AB - Protein molecules known as Growth Factors (GFs) appear to play an important regulatory role in a number of CNS functions. In particular Nerve Growth Factor (NGF), the best characterized among about 30 GF molecules, is endowed with specific activities on cholinergic and peptidergic CNS neurons. Indexes of neurobehavioral maturation are accelerated in the mouse by neonatal NGF exposure, while a similar treatment with EGF exerts both growth-promoting and growth inhibiting effects on somatic and behavioral development. Scopolamine hyperactivity is enhanced around weaning by NGF pretreatment. Data are discussed along with (a) NGF prevention of cholinergic system damage and (b) the molecular mechanism of endogenously-triggered CNS repair processes. PMID- 2234547 TI - Risk assessment: the insidious nature of neurotoxicity and the aging brain. AB - Neurotoxicology is a fertile source of ambiguities. They complicate the conventional risk assessment process, whose current procedures and models were designed to accommodate a unitary endpoint and mechanism. All of these ambiguities are multiplied by their interaction with aging because many manifestations of neurotoxicity, such as impaired sensory acuity, mimic the natural course of aging. With aging as a model, modifications of the risk assessment paradigm have been designed. These modifications take the form of adaptations able to accommodate the unique properties of neurotoxicity. Properties such as progressive declines in function, the late impact of prenatal damage, multiple endpoints, variations in exposure pattern, reversibility, and population shifts in performance are explicitly recognized by these adaptations. PMID- 2234548 TI - Memory, synaptic plasticity and neurotoxins. AB - Most neurotoxins induce serious impairments in cognitive or intellectual functioning; therefore, the ability of the individual to learn and remember forms a critical component of neurotoxin assessment. In depth investigations of neurotoxin-induced cognitive deficits have assisted in pinpointing the neural site of toxin activity. However, specific impairments in learning and memory can depend on the developmental stage at which the individual is exposed to the toxin, and certain neurotoxins show cognitive lifespan selectivity. There appears to be a basic sequence of events underlying neural development and information storage, and neurotoxins may disrupt this neuronal sequel critical for the storage or expression of "ancestral" or "environmental" memories. Certain primary rules govern the orderly development of the nervous system; these rules or mechanisms allow the expression of "ancestral memories" concerning neuronal differentiation and primitive behaviors. Following birth, these same mechanisms have been retained in a less robust form to allow learning and information storage, or the retention of "environmental memories." Neurotoxins which disrupt learning and memory capacities appear to interfere in this basic sequence of events, with the specific outcome depending on when during lifespan development the neurotoxin intervenes. PMID- 2234549 TI - Comparative sensitivity of neurobehavioral tests for chemical screening. AB - Guidelines for conducting neurobehavioral tests of motor activity, schedule controlled operant performance, and a functional observational battery (FOB) were published by the U.S. EPA Office of Toxic Substances (1985). We have utilized a specific FOB protocol in conjunction with motor activity measured in a figure eight maze and performance maintained under a fixed-interval schedule of reinforcement to determine the acute effects of chemicals which produce different syndromes of intoxication in rats (chlordimeform, carbaryl, pentobarbital, triadimefon, nicotine, and 3-acetyl pyridine). The results showed that for each compound there was a substantial degree of overlap in the dose range of effectiveness across the different tests. In all cases, however, the lowest effective dose identified using the FOB was equal to or less than that provided by motor activity and operant tests. For most compounds, motor activity and operant performance were equally sensitive. Nicotine and triadimefon, however, increased the rate of operant responding at lower doses than those that affected motor activity. The time course of each chemical appeared similar across tests with one exception. 3-Acetyl pyridine produced clear effects in the FOB throughout testing (up to three weeks) whereas recovery was evident within one week using motor activity and operant performance. FOB and motor activity testing can be easily integrated into ongoing toxicity studies. On the other hand, the traditional approach to testing the effects of chemicals on operant performance requires prior food or water deprivation, and time for training the animals and establishing a stable level of performance. In the context of hazard identification (i.e., testing for the effects of unknown chemicals) the FOB and motor activity may be expected to adequately detect neurotoxicity. Operant performance may be more valuable in characterizing the actions of identified neurotoxicants. PMID- 2234550 TI - Neonatal exposure to DDT and its fatty acid conjugate: effects on cholinergic and behavioural variables in the adult mouse. AB - We have recently observed that DDT and a DDT metabolite, DDOH, conjugated to a fatty acid, palmitic acid, DDOH-PA, affects muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice during rapid brain growth. This early exposure of the neonatal mouse also affects the behaviour of the animals as adults. When DDT and DDOH-PA was given as a single low oral dose of 1.4 mumol/kg body weight, DDT (0.5 mg), DDOH-PA (0.7 mg) and a 20% fat emulsion vehicle (10 ml) per kg body weight to 10-day-old NMRI mice, behavioural tests at adult age of four months, indicated disruption of a simple, non-associative learning process, i.e. habituation, in both DDT and DDOH-PA treated mice. There was also a significant increase in the potassium evoked release of ACh from slices of cerebral cortex and a tendency towards a decrease in the density of MAChR in mice receiving DDT. These effects in the adult mice could not be correlated to the concentration of DDT in the adult brain since DDT one month after its administration to the 10-day-old mouse no longer is present in the brain. PMID- 2234552 TI - Toxic effects of cocaine to the cardiovascular system in conscious and anesthetized rats and rabbits: evidence for a direct effect on the myocardium. AB - The cardiovascular toxicity of cocaine is complex because it has local anesthetic properties, central nervous system stimulatory effects, as well as cardiac effects. Recreational use of this drug has increased recently, but the precise mechanism of sudden cardiac death induced by cocaine is not known. The primary objective of this work was to test for a direct cardiovascular toxicity of cocaine. Rats and rabbits were anesthetized, and the femoral vein and artery were cannulated for drug infusion and blood pressure monitoring. Different doses of cocaine (0.3, 1, 3, 10 mg/kg) were infused. For conscious animal experiments, the animals were allowed to recover from the anesthesia and then were subjected to cocaine. Low doses of cocaine (0.3 and 1 mg/kg) increased systolic as well as diastolic pressure in conscious rats and rabbits. In anesthetized rats and rabbits, the same dose of cocaine increased blood pressure with a decrease in heart rate. With the high doses of cocaine (3 and 10 mg/kg), all cardiac parameters were reduced in both rats and rabbits. In isolated rabbit hearts, cocaine decreased all cardiac parameters. Based on the fact that high doses of cocaine severely depressed all cardiac parameters and its effect on the isolated heart, cocaine-induced sudden cardiac death appears to be due to a primary effect on the myocardium. PMID- 2234551 TI - Acute cardiovascular toxic effects of copper in anesthetized rabbits. AB - Copper deficiency is linked to many types of cardiovascular diseases. Copper toxicity may not be common, but it produces cardiac problems and even lethality. However, little is known about the precise mechanism of cardiotoxic action of copper in mammals. In an effort to characterize the cardiovascular effects and potential toxic action of copper, white New Zealand rabbits were instrumented for the measurement of cardiovascular parameters under urethane anesthesia. Left ventricular pressure and its dP/dt as well as the sympathetic efferent renal nerve activity were also monitored continuously before, during and after the injection of various doses of copper. Low doses of copper (3 mg/kg or less) increased blood pressure with a slight reduction in heart rate. There was also a transient increase in cardiac contractile force as shown by an increase of dP/dt with a reduction in sympathetic renal efferent nerve activity. However, high doses of copper (10 mg/kg or higher) decreased these cardiac parameters, which led to a state of shock, 90 seconds after the copper treatment. There was a compensatory increase in respiration rate and renal nerve activity during the shock. Thus, the data suggest that copper initially activates peripheral organs such as the heart and subsequently produces a distinct inhibitory action on sympathetic outflow, which is related to the toxic action of this metal. PMID- 2234553 TI - Ethanol inhibition of spontaneous calcium release from isolated sarcoplasmic reticulum of alcoholic rats. AB - Ethanol is a well-recognized cause of muscle damage in humans. In vitro, ethanol decreases muscle fiber twitch tension by a mechanism unrelated to the electrical events of the motor endplates or muscle surface membranes. One possible explanation for this effect is a primary ethanol effect on calcium release from the sarcoplasmic reticulum (SR). Ethanol has been shown to progressively decrease a form of calcium release from isolated SR vesicles seen in vitro in the presence of high phosphate concentrations ("spontaneous calcium release"). In this study, ethanol is shown to have similar inhibiting effects on spontaneous calcium release from sarcoplasmic reticulum isolated from alcoholic rats and from pair fed controls. This suggests that membrane adaptation to chronic ethanol exposure, such as has been described for brain and liver membranes, does not produce tolerance to ethanol effects on spontaneous calcium release in sarcoplasmic reticulum. PMID- 2234554 TI - Zinc nutrition in fetal alcohol syndrome. AB - Because alcohol has an adverse effect on zinc homeostasis, this study was designed to study if zinc content of the diet modifies the severity of fetal alcohol syndrome in a mouse model. The effect of varying zinc intake on the progeny of pregnant mice fed a liquid diet containing 15% of the calories as ethanol was studied. Prenatal mortality was higher when the mothers consumed alcohol with inadequate zinc intake. Because of the adverse effect of alcohol on zinc homeostasis and because zinc deficiency has been shown to potentiate alcohol embryopathy, one group was given zinc supplementation to four times the Recommended Dietary Allowance. Supplemental zinc above the Recommended Dietary Allowance was not protective and appeared to have an adverse effect on fetal weight and prenatal mortality. These results suggest that zinc intake should be optimized during pregnancy but that zinc supplementation above the Recommended Dietary Allowance does not reduce the incidence or severity of fetal alcohol syndrome. PMID- 2234556 TI - Assessment and management of cervical intraepithelial neoplasia. AB - Although cervical intraepithelial neoplasia (CIN) once was thought to be a clinical problem primarily for older women, data reveal an alarming rise of this condition among younger women. The gains made in decreasing the incidence of cervical cancer have been tempered by the steadily increasing incidence of its precursor state, CIN. Because of increasing evidence of the association of the human papillomavirus (HPV) with cervical cancer and CIN, this virus is of particular concern. Colposcopy is a valuable method for evaluating CIN that has been indicated on Pap, as well as for identifying HPV. Since having an abnormal Pap and undergoing colposcopic examination may be stressful, the clinician can play a significant role in helping the client cope with the process of evaluation and treatment of abnormal Paps in addition to controlling cervical cancer. PMID- 2234555 TI - Otitis media: an overview of acute and chronic disease. AB - Otitis media is the most prevalent illness affecting the pediatric population. Each year in the United States there are 30 million visits to pediatricians for the treatment of otitis media infections and their sequelae, at a cost of $1 billion in health care dollars. This article offers a discussion of the factors that predispose children to otitis media, with emphasis on diagnosis and treatment. The clinical presentation, disposition and associated morbidity of common complications are also discussed. PMID- 2234557 TI - Diagnosis and management of cluster headaches. AB - Cluster headaches are vascular headaches that predominantly affect males and occur frequently, with cyclic regularity. Treatment is predominantly pharmacological in nature and is divided into symptomatic and prophylactic relief. This article discusses the pathogenesis, clinical features, and current prophylactic and symptomatic treatments used with cluster headaches. PMID- 2234558 TI - Antibiotic therapy for epididymitis clarified. PMID- 2234560 TI - Furosemide for pulmonary edema. PMID- 2234559 TI - A tragic breach in the standard of care. PMID- 2234561 TI - Making it better. PMID- 2234562 TI - Improving nurse/doctor communications. PMID- 2234563 TI - The mouth organ. PMID- 2234564 TI - Complying with vaccine law will help prevent errors. PMID- 2234565 TI - The need to laugh. PMID- 2234566 TI - Consent for treatment. Lover's rights. PMID- 2234567 TI - Caring for patients with intracranial tumors. PMID- 2234568 TI - Managing C.H.F. at home. PMID- 2234569 TI - Working with a transhepatic biliary catheter. PMID- 2234570 TI - Choosing a leadership style that fits. PMID- 2234571 TI - Action stat! Tetanus. PMID- 2234573 TI - Fast facts about Fax. PMID- 2234572 TI - Today's insulins. What you and your patient need to know. PMID- 2234574 TI - David had all but surrendered to death ... until a nurse stepped in. PMID- 2234576 TI - Assessing cardiac emergencies. PMID- 2234575 TI - Working with kids who have cancer. PMID- 2234577 TI - When nurses are addicted to drugs. Confronting an impaired co-worker. PMID- 2234578 TI - Get on the right track with Z-track injections. PMID- 2234579 TI - Respiratory alkalosis. Pathophysiology, signs, and symptoms. PMID- 2234580 TI - How to assess deep tendon reflexes. PMID- 2234581 TI - Controlling the flow. Electronic infusion devices. PMID- 2234582 TI - Making room for love. PMID- 2234583 TI - Determining the cause of postoperative fever. PMID- 2234584 TI - Reviewing A.I.D.S. PMID- 2234585 TI - Research in nurse education. PMID- 2234586 TI - Cancer nursing: learning to cope with an artificial limb. PMID- 2234587 TI - Cancer nursing: biological therapy. PMID- 2234588 TI - Cancer nursing: management of constipation. PMID- 2234591 TI - Racism: just a hue and cry? PMID- 2234590 TI - The Edinburgh experience. PMID- 2234589 TI - Cancer nursing: a history of pain. PMID- 2234592 TI - Project 2000 Australian style. PMID- 2234593 TI - Patient care--or repression? PMID- 2234594 TI - Homes fit for nurses. PMID- 2234595 TI - PREPP: what it will mean. PMID- 2234596 TI - Theatre nursing. Involving the parents. PMID- 2234597 TI - Theatre nursing. Pre-op visits: why they don't happen. PMID- 2234598 TI - Theatre nursing. Operation Green. PMID- 2234599 TI - Returning to nursing. PMID- 2234601 TI - Central Birmingham: the personal touch. PMID- 2234602 TI - I thought I was discharged. PMID- 2234600 TI - Creative arts as therapy. PMID- 2234603 TI - Identity crisis. PMID- 2234604 TI - Theatre nursing. Developing the role of the nurse. PMID- 2234605 TI - Pharmacologic control of aberrant behavior in the mentally retarded: toward a more rational approach. AB - Drugs are frequently used to control aberrant behavior in the mentally retarded. However, despite decades of research, this approach to behavioral management has had very limited success. Slow progress in this area can be attributed, in part, to the lack of a theoretical framework to guide research. The main purpose of this review is to integrate clinical research in this area with evidence concerning the neurochemical mechanisms that mediate aberrant behaviors. It is concluded that a theoretical framework that takes into account the biological mechanisms that underlie disordered behavior and the actions of drugs provides the basis for a more rational approach to the development of pharmacological therapies in the mentally retarded. PMID- 2234606 TI - Central effects of CRF on metabolism and energy balance. AB - CRF is recognised for its actions on pituitary ACTH release, but also has direct effects within the brain which are important in mediating physiological responses to stress. Behavioral effects of CRF include increased locomotor activity and inhibition of food intake and its actions on metabolism are mediated mainly by activation of the sympathetic nervous system. CRF appears to be important in the regulation of energy balance and body weight, influencing both food intake and sympathetically-mediated thermogenesis. A defect in the synthesis or release of CRF has been implicated in the development of obesity in laboratory animals, since the condition is alleviated by adrenalectomy, hypophysectomy or exogenous CRF treatment. Recent data have revealed an additional role for CRF as a mediator of the neuroendocrine and metabolic responses to immune signals, particularly cytokines. The central actions of CRF are independent of the pituitary but may involve release of proopiomelanocortin products within the brain. CRF is thus emerging as an important integrator of the physiological responses to stress, infection and immunity, a finding which may have important implications for future therapies. PMID- 2234607 TI - Behavioral adaptations to pathogens and parasites: five strategies. AB - The ever present threat of viral, bacterial, protozoan and metazoan parasites in the environment of wild animals is viewed as responsible for the natural selection of a variety of behavioral patterns that enable animals to survive and reproduce in this type of environment. Several lines of research, some quite recent, point to five behavioral strategies that vertebrates utilize to increase their personal or inclusive fitness in the face of parasites (broadly defined to include pathogens). These are: 1) avoidance of parasites; 2) controlled exposure to parasites to potentiate the immune system; 3) behavior of sick animals including anorexia and depression to overcome systemic febrile infections; 4) helping sick animals; 5) sexual selection for mating partners with the genetic endowment for resistance to parasites. The point is made that to consider a behavioral pattern as having evolved to serve a parasite control function the parasite or causative agent should be shown to adversely impact the animal's fitness and the behavior in question must be shown to help animals, or their offspring or group mates, in combating their exposure, or reducing their vulnerability, to the parasite. PMID- 2234608 TI - The neural mechanism of declarative memory consolidation and retrieval: a hypothesis. AB - This paper proposes a new theory addressing the neural mechanism of declarative memory consolidation and retrieval. The premise of the theory is that the cortex is responsible for the storage of declarative memory while the medial temporal lobe is responsible for the consolidation and retrieval of declarative memory. The theory suggests that the medial temporal lobe can only accomplish its functions related to memory by hierarchically and cooperatively regulating the descending limbic system, including the hypothalamus, epithalamus, septum, mammillary bodies and the bed nucleus of the stria terminalis. These descending limbic structures, together with the amygdala, further send efferents to the four ascending NA, 5-HT, DA and ACh systems. It is these four ascending extrathalamic regulatory systems that provide the feedback neural pathways to the cortex and regulate the processes of memory consolidation and retrieval in the cortex. Therefore, the coupling of these descending limbic structures to the ascending NA, 5-HT, DA and ACh systems completes the neural circuits responsible for the consolidation and retrieval of new declarative memories. This neural mechanism of declarative memory consolidation and retrieval is universal to all species in higher mammals. PMID- 2234609 TI - Neuroendocrine mechanisms involved in regulation of body weight, food intake and metabolism. AB - Body weight regulation is the result of food intake and energy expenditure. The central nervous system (CNS), and in particular, the hypothalamus, controls food intake as well as metabolism, the latter mainly by autonomic effects on the islet of Langerhans, hepatocytes and adipocytes. Body weight, more precisely body fat content, is probably controlled by a feedback mechanism in which insulin, released from the B cell of the islet of Langerhans, plays a key role. The islet of Langerhans is an intricate neuroendocrine unit in which the release of glucagon, insulin, and somatostatin from A, B, and D cells, respectively, is controlled by the CNS via a rich autonomic innervation. In addition, the endocrine cells of the pancreas influence each other by paracrine actions. The CNS control of the islets shapes the plasma insulin and blood glucose profiles during the circadian cycle and thereby regulates the nutrient flow to the different tissues in the body. Thus, the CNS structures involved in regulation of body weight and food intake control also metabolism. The mechanisms contributing to match food intake and the needs of metabolism are discussed. PMID- 2234610 TI - Pancreatic glucagon signals postprandial satiety. AB - The hypothesis that prandial increases in circulating pancreatic glucagon initiates an important peripheral satiety signal is reviewed. Glucagon administration at the beginning of meals reduces the size of test meals in animals and humans and reduces the size of spontaneous meals in rats. Exogenous glucagon may also interact synergistically with cholecystokinin to inhibit feeding. These appear to be satiety effects because they are behaviorally specific in rats and subjectively specific in humans. Glucagon's pharmacological satiety effect is complemented by compelling evidence for a necessary contribution of endogenous glucagon to the control of meal size: administration of glucagon antibodies increases both test and spontaneous meal size in rats. Under many, but not all, conditions exogenous glucagon's satiety effect appears to originate in the liver and to be relayed to the brain via hepatic vagal afferents. Analysis of the central processing of this signal, however, has barely begun. How glucagon changes are transduced into neural afferent signals also remains an open question. The only hypothesis that has been extensively tested is that stimulation of hepatic glucose production initiates the satiety signal, but this is neither convincingly supported nor clearly rejected by currently available data. It is also not yet clear whether glucagon contributes to some forms of obesity or has potential use as a therapeutic tool in the control of eating disorders. Of the several proposed controls of hunger and satiety, glucagon appears to be one of the most likely to be physiologically relevant. This encourages further analysis of its behavioral characteristics, its neural mechanisms, and its clinical potential. PMID- 2234611 TI - A review of the physiological bases of the anorexic action of phenylpropanolamine (d,1-norephedrine). AB - Phenylpropanolamine (PPA) is a phenethylamine that induces a variety of effects including anorexia and weight loss. The present review compares the acute anorexic effects of PPA with those of amphetamine in animals and humans, describes the persistent chronic effects of PPA on feeding as well as differences in anorexic potency between the norephedrine enantiomers (d-norephedrine less than 1-norephedrine) and summarizes the generality of PPA anorexia. The review also describes the putative mechanisms by which PPA is thought to reduce feeding behavior including alteration of gastric emptying and interaction with central nervous system neurons. PMID- 2234612 TI - The rising incidence of congenital syphilis: back to the future. PMID- 2234613 TI - Crack cocaine: ripples of a rock in a pond. PMID- 2234614 TI - Syphilis among parturients at an inner city hospital: association with cocaine use and implications for congenital syphilis rates. AB - The frequency of positive cord blood rapid plasma reagin (RPR) tests among newborns at an inner city hospital and associations with maternal cocaine use, prenatal care, and adequacy of syphilis therapy were retrospectively assessed. The incidence of positive cord blood RPRs increased from 1.1% of all live births in 1985 to 3.4% in 1988. In 1987, 98 babies were born with positive cord blood RPRs; 86 of their charts were available for review. Four infants had false positive RPRs, and one patient delivered twins, leaving 81 mothers who could be evaluated. Almost 37% of these patients had had no prenatal care. More than 55% had inadequate or not therapy for syphilis. Of these, only 17.4% had prenatal care. Slightly more than 40% of patients acknowledged using drugs during pregnancy, 87.9% of whom used cocaine. Among the patients who used drugs, 75.8% received no prenatal care, in contrast to 10.4% of mothers who did not use drugs (p less than 0.001). It appears that drug use, particularly use of cocaine, is associated with low levels of utilization of prenatal services and inadequate therapy for syphilis. This may lead to increased risk of congenital syphilis in newborns. PMID- 2234615 TI - The prevalence of marijuana (cannabis) use and dependence in cocaine dependence. AB - In a retrospective and prospective study using DSM-III-R criteria for substance dependence in 232 inpatients and 51 outpatients, the clinical suspicion that cocaine addicts use other drugs including marijuana was confirmed. As many as 53% of cocaine addicts diagnosed by DSM-III-R criteria for cocaine dependence qualified for a diagnosis of cannabis dependence. The reports regarding marijuana and other drug dependence among cocaine addicts have been few and inconclusive. The diagnosis of other drug use and dependence in cocaine dependence has importance with regard to prognosis and treatment. This study found a high prevalence of marijuana (cannabis) dependence in patients with cocaine dependence. PMID- 2234616 TI - The public health consequences of crack cocaine. PMID- 2234617 TI - Position paper of the Associated Medical Schools of New York on HIV testing and access to treatment. PMID- 2234618 TI - Gas warfare: military-medical responsiveness of the Allies in the Great War, 1914 1918. PMID- 2234620 TI - Eosinophilia-myalgia syndrome and L-tryptophan. PMID- 2234619 TI - Crack abuse and asthma: a fatal combination. PMID- 2234621 TI - Neurocutaneous manifestations of neurofibromatosis-2. PMID- 2234622 TI - Defining brain death. PMID- 2234623 TI - Trade and generic names of drugs. PMID- 2234624 TI - A neglected resource. PMID- 2234626 TI - The community health worker program. PMID- 2234625 TI - Reversible hypoxic cerebral edema in severe hemolytic crisis. PMID- 2234627 TI - Skin cancer prevention. PMID- 2234628 TI - Cervical cancer in New York State. PMID- 2234629 TI - [General supervision of practice and agency placement nurses]. PMID- 2234630 TI - [Choose a theoretical framework--choose Orem]. PMID- 2234631 TI - [Dying a little each day]. PMID- 2234632 TI - [Pakistan. The beginning of a new time for the nursing profession]. PMID- 2234633 TI - [What do you know about prostate cancer?]. PMID- 2234634 TI - [Alcohol and community action]. PMID- 2234636 TI - [To stop conjugal violence]. PMID- 2234635 TI - [Psychiatric day hospitals]. PMID- 2234637 TI - An illustrious past, but our future needs rethinking. PMID- 2234638 TI - [Career plans in the clinical milieu]. PMID- 2234639 TI - [Drug-food interactions]. PMID- 2234640 TI - Evaluation of standards of practice for general practitioners using eight hypothetical cases. AB - Concerns about the quality of primary care in New Zealand have increased over recent years as the scarcity of research in this field has become more apparent. A survey was undertaken among 132 general practitioners in Otago and Southland to gauge the degree of consensus of care for eight hypothetical cases. An 87.3% response rate was obtained. The year of graduation of the respondents was a significant factor in determining the response to the choice of management options for the paediatric sore throat and the benign hypertension cases. A variation in treatment of a 65 year old with epigastric pain was seen between rural and urban practitioners, with the cluster containing the most rural practitioners being least likely to undertake detailed diagnostic procedures. PMID- 2234641 TI - Dependency levels of people in aged care institutions in Auckland. AB - Between January and June 1988, a survey of 7516 people in aged care facilities in the Auckland region (99.4% response rate) was undertaken to ascertain the extent and provision of care for elderly people requiring ongoing care in order to make comparisons with other centres in New Zealand. Information was gathered about their ability to perform various activities of daily living by staff members who completed a structured precoded and pretested questionnaire for each resident or patient. Overall levels of dependency were also assessed as part of the questionnaire: 13% were assessed as requiring long stay hospital care, 48% had moderate or appreciable dependency, and the remainder had some dependency (23%) or none at all (16%). Almost one quarter (23%) of the 5213 residents in old people's homes were rated as apparently independent. Of people in religious and welfare residential homes, 38% were rated as independent whereas in commercial rest homes 12% of people were classified in this way. This high level of apparent independence in religious and welfare homes is the main aspect in which the Auckland long term care scene is distinct from other regions in the country. PMID- 2234642 TI - Silent myocardial ischaemia. PMID- 2234643 TI - The spectrum of systemic candidiasis at Auckland Hospital. AB - Systemic candidiasis is uncommon. We reviewed our experience with this disease from the infectious disease unit, Auckland Hospital, between 1982 and 1988, because many of these patients are referred to us. We then selected 11 of them to highlight particular presentations, diagnostic or management issues. We included both compromised and noncompromised patients from medical and surgical services. Candida albicans was the most common cause, but we also saw patients infected with C glabrata, C parapsilosis, and C tropicalis and present them to exemplify their different clinical presentations. Demonstrable fungaemia is uncommon in patients with systemic candidiasis, serological techniques are both insensitive and nonspecific and patients are often too ill from underlying disease to allow for invasive diagnostic procedures. Thus diagnosis is often difficult. Parenteral amphotericin B with or without 5-fluorocytosine is still the main antifungal treatment. Triazole antifungals may change that in the future. Systemic candidiasis retains a high mortality: careful individualised management of patients may improve mortality and morbidity. PMID- 2234644 TI - Asthma and its management at a student health service. AB - Of 96 asthmatic students 62 said their asthma had not required them to give up any activity but only seven said it had not interfered in some way with their sport. Thirty-nine regarded their asthma as an annoyance and 13 of these were angered by it. Fifty-seven respondents took treatment continuously and the most favoured agent in attacks was salbutamol. Peak flow meters were not used regularly except by six students. About two-thirds had significant deficiencies in their knowledge of asthma and the most popular source of information was the general practitioner. Only 30 had read the Asthma Foundation pamphlets. PMID- 2234645 TI - Acute transfusion reactions. AB - We reviewed 1500 acute transfusion reactions that were reported to the Auckland Regional Blood centre over a 7 year period, from approximately 440,000 transfusions. The majority of reactions were to red cells, and these had the highest reaction incidence per unit (0.73%) of all blood products. The reaction incidence per unit transfused for plasma was 0.1%, for stable plasma protein solution 0.01%, and for platelets 0.04%. The majority of symptoms reported were mild and transient. The commonest were fever (72%), rigors (33%), and rash or urticaria (30%). Although more serious reactions were reported such as angioedema, hypotension and pulmonary oedema, none of these were severe, as judged from the data reported to the centre. There were two transfusion related deaths during the study period, one due to an ABO incompatible transfusion, the other due to bacterial contamination of a unit of blood. Leucocyte agglutinins or antibodies were detected in 29% of those with a febrile reaction, but were also detected in 22% of those who remained afebrile. Serological abnormalities that may have accounted for the reaction were only detected in 12 patients six of whom had autoantibodies. As laboratory investigation reveals little that accurately defines the aetiology of a reaction, a rationalisation of the investigation into acute transfusion reactions is suggested. PMID- 2234646 TI - Poor participation of nulliparous women in a low dose aspirin study to prevent preeclampsia. AB - Only four of 39 nulliparous women agreed to participate in a placebo controlled study of low dose aspirin therapy to prevent preeclampsia. The major reason for nonparticipation was fear the aspirin would harm the fetus (30 of 35 women). Twenty-four women felt public promotion of a healthy lifestyle influenced their nonparticipation. No woman felt any practical problems related to the study impeded their recruitment and all but one woman felt the study was important and worthwhile. Eleven women considered any drug therapy or research in pregnancy was anathema. As a result of the low response rate a multicentered study was not feasible. Unless new approaches to research are developed, scientific advances in obstetric practice in New Zealand may depend only on research conducted overseas. PMID- 2234647 TI - The Cartwright inquiry. PMID- 2234648 TI - Tobacco advertising and consumption. PMID- 2234649 TI - Indentured slavery. PMID- 2234650 TI - HIV testing. PMID- 2234651 TI - Melanoma and polyunsaturated fat; cancer and diet. PMID- 2234652 TI - Strategic ethics. PMID- 2234653 TI - Thin membrane nephropathy. PMID- 2234654 TI - Doxorubicin-associated hyperpigmentation. PMID- 2234655 TI - Fluoridation and caries. PMID- 2234656 TI - Does a low serum potassium predispose to admission to coronary care? PMID- 2234657 TI - Double gloving during surgery: a technical tip. PMID- 2234658 TI - Treatment of cutaneous larva migrans. PMID- 2234660 TI - Auckland revisited. Busy, busy, busy. PMID- 2234659 TI - Letters from Romania. PMID- 2234662 TI - Auckland revisited. Bureaus in business. PMID- 2234661 TI - Auckland revisited. Baby boom. PMID- 2234663 TI - Nursing, mental health and the community. PMID- 2234664 TI - The price of participation. PMID- 2234666 TI - After the act. PMID- 2234665 TI - Professional? Industrial? Closing the gap. PMID- 2234667 TI - Care of the elderly: sound sleep. PMID- 2234669 TI - Save time and money on new products. PMID- 2234668 TI - The decision wasn't made alone... PMID- 2234671 TI - Emergency department liability: general legal issues for nurses. PMID- 2234670 TI - Closing the gap between school and service. PMID- 2234672 TI - National practice guidelines: what do they mean for nurses? PMID- 2234674 TI - Trust: essential for delegation. PMID- 2234673 TI - Model Medicare physician fee schedule published. PMID- 2234675 TI - Peer interviews: sharing the hiring process. PMID- 2234676 TI - Health patterns as DRG outlier predictors. PMID- 2234677 TI - A study of nursing documentation. PMID- 2234678 TI - Daily nursing documentation can be quick and thorough! PMID- 2234679 TI - Charting for accountability. PMID- 2234681 TI - Home health challenges: paperwork vs. peoplework. PMID- 2234680 TI - New nurse managers: Part I--Orientation for the 1990s. PMID- 2234682 TI - What keeps nurses in nursing? PMID- 2234683 TI - MBO theory versus the real world. PMID- 2234684 TI - Patient classification interrater reliability. PMID- 2234685 TI - Attitude: the new posture for the nineties. PMID- 2234686 TI - Power: from commanding turf to generating excellence. PMID- 2234687 TI - Iconodontalgia VI. PMID- 2234688 TI - Computers? PMID- 2234689 TI - Autologous blood: the safest alternative. PMID- 2234691 TI - Albany, where the action is. PMID- 2234690 TI - Decreasing the density of dark radiographs--a lost art. AB - The purpose of this paper is to describe a procedure that appears to have been lost with time and that reduces excess density [immaterial of the cause] on radiographs. This results in radiographs of greatly improved diagnostic quality. This procedure results in avoiding retakes resulting in a lower radiation dose to the patient and a saving of time. This procedure should not be considered as a substitute for poor radiological or processing techniques. PMID- 2234692 TI - Clarifying "managed care". PMID- 2234693 TI - International Commission on Radiation Protection. PMID- 2234694 TI - Technetium-99m antimony sulphide colloid lymphoscintigraphy of the prostate by direct transrectal injection. AB - Laterality of prostatic lymphatic drainage was successfully assessed in nine patients with prostatic carcinoma after direct unilateral transrectal injections of 99Tcm-antimony sulphide colloid by Franzen needle. Pelvic lymphatic drainage was equally divided between ipsilateral, contralateral and bilateral patterns. The frequent observation of radiocolloid migration to contralateral lymph node groups in patients with prostate carcinoma, including those with primary disease localized clinically to a single lobe of the prostate, indicates the potential for contralateral pelvic lymph node metastases in this population. This finding may be important in determining the appropriate surgical staging and treatment of patients with prostate carcinoma. The clinical applicability of lymphoscintigraphy in the evaluation of metastatic spread and in lymph node biopsy planning requires further study. PMID- 2234695 TI - Anti-melanoma antibodies bind preferentially to diploid metastases in immunoscintigraphy. AB - Immunoscintigraphy with 99Tcm-labelled anti-melanoma monoclonal antibody F(ab')2- fragments was performed in 23 patients with histologically verified metastatic melanoma. Immunoscintigraphy was positive in 14 patients and all known metastases were detected in eight patients, five of whom had only one lesion. Lesion localization and detectability were as follows: 12/13 (92%) cutaneous and subcutaneous, 11/14 (79%) lymph node, 5/7 (71%) bone, 3/6 (50%) lung and 1/5 (20%) abdominal metastases were visualized. Despite its high specificity--no false positive immunoscintigrams--the low sensitivity of this method in detecting deep metastases hampers its usability. The false negative results were not due to lack of antigen expression as positive immunostaining results were observed also in specimens from patients with negative immunoscintigrams. Flow cytometric analysis of the metastases revealed that in 7/8 (88%) patients with diploid tumours had positive immunoscintigrams but only 7/15 (47%) patients with aneuploid tumours. These results show that the diagnostic accuracy of melanoma immunoscintigraphy can be improved by selecting patients not only by testing for the antigen but also on the basis of DNA analysis of an accessible lesion. PMID- 2234697 TI - Cortical cerebral blood flow in HIV-1-related dementia complex. AB - Dementia complex is a syndrome that affects a high percentage of AIDS patients. Neuroradiological findings may be non-specific and the diagnosis can be difficult in its earlier stages. Preliminary radionuclide studies have recently reported derangements of regional cerebral blood flow (CBF) which may be present before overt anatomical injury. This study reports on cortical and cerebellar CBF changes in 26 patients studied with 99Tcm-HM-PAO and single photon emission computed tomography (SPECT). Extensive cortical CBF derangements were observed in all patients and an evident cerebellar hypoperfusion was also present in three. The prevalence of hypoperfusion was highest in the frontal and parietal lobes. The extension of the hypoperfusion showed a highly significant correlation with the severity of the dementia complex (P less than 0.01 by chi 2 test). The SPECT also showed hypoperfused areas in three patients with normal CT scans and in two patients with normal MRI scans. These results confirm previous preliminary reports on the high prevalence of cortical hypoperfusion in dementia complex and suggest the use of this radionuclide technique to assist in the early diagnosis and follow-up of AIDS patients, especially when CT and MRI are still normal. PMID- 2234696 TI - Radionuclide studies of left ventricular function in normal subjects. AB - The effects of age and exercise on cardiac function in a normal male population have been assessed by ECG-gated radionuclide ventriculography. Fifty-nine subjects aged from 25 to 54 years were studied (mean 44 +/- 10 S.D. years). Resting left ventricular ejection fraction (LVEF) was 0.54 +/- 0.07 and this increased by 0.07 +/- 0.05 during supine submaximal exercise at 75 watts. The mean increase in cardiac output on exercise was 93 +/- 30%. Stroke volume increased on exercise by 23 +/- 13% and end-systolic volume decreased by 10 +/- 16%. There was a weak correlation (P less than 0.05) between age and change in LVEF on exercise but the increase in cardiac output on exercise was not age dependent. It is important to use an age matched control population in any study of cardiac function. PMID- 2234699 TI - Difficulties in detecting osteitis in the diabetic foot. PMID- 2234698 TI - 67Ga-scintigraphy for evaluation of AIDS-related intestinal infections. AB - This study was designed to evaluate the role of 67Ga-scintigraphy in AIDS-related intestinal infections. Seventeen out of twenty-five HIV-positive patients (68%) primarily investigated with 67Ga-scans to screen for opportunistic pneumonia presented pathologic abdominal 67Ga-uptake which was, in most cases, due to proven opportunistic intestinal infection (cytomegalovirus, atypical mycobacteria, cryptosporidiosis etc.). The correlation of abdominal with pulmonary findings has shown that AIDS-related intestinal infections and opportunistic pneumonia may occur concomitantly in the majority cases (11/17). In 6/17 patients positive abdominal findings were observed without opportunistic pneumonia at the same time. Gallium imaging of the abdomen has shown to identify successfully the most common extrapulmonary sites of HIV-related infections. Thus, abdominal imaging or whole body scintigraphy should be a mandatory part of each 67Ga-scan in patients with HIV infection, even if it was primarily performed to screen for opportunistic pneumonia only. Knowledge of multilocular opportunistic infections, usually caused by different pathogens, is clinically important for further diagnostic and therapeutic management. PMID- 2234700 TI - Prenatal diagnosis of fetal tumors by ultrasonography. AB - Fetal tumors lead to serious illness or even death in the fetal or neonatal period. Problems vary from severe hydrops to underdevelopment of fetal organs. In some instances a tumor may cause mechanical obstruction during the birth process. Polyhydramnios frequently develops. Adequate prenatal diagnosis is of utmost importance. Timely detection of the fetal tumor prevents traumatic birth and postnatal care and treatment can be scheduled. This report is a review of the relevant recent literature and the tumors detected in our ultrasound unit between 1982 and 1988. The ultrasonographic appearance, clinical course, and differential diagnosis of the tumors are discussed. PMID- 2234701 TI - Recurrent miscarriage: a review of current concepts, immune mechanisms, and results of treatment. PMID- 2234702 TI - Retroperitoneal soft tissue sarcomas: a review of the literature. AB - The English language literature on retroperitoneal sarcomas published between 1981 and 1988 has been reviewed. The histology, different prognostic factors, value of imaging techniques, and need for multidisciplinary management are discussed. Complete surgical excision with tumor-free margins confirmed by histology is essential if long-term survival and local control are to be achieved. In many cases resection of adjacent organs is required as most patients present with advanced, aggressive local disease. The roles of adjuvant radiotherapy and chemotherapy in the treatment of retroperitoneal sarcomas are uncertain and must await further controlled, randomized, prospective studies. PMID- 2234703 TI - Sexuality and reproduction in spinal cord injured women. AB - Sexuality, reproduction, and childbearing are essential issues for the spinal cord injured women. The medical complications, including urinary tract infections, anemia, pressure sores, sepsis, and autonomic hyperreflexia are significant in each of these areas with both physical as well as emotional ramifications. Patient and family education is of primary importance in both anticipating as well as dealing with the potentially serious consequences. A consultant knowledgeable in the problems of the spinal cord injured can be of utmost benefit especially in the labor and delivery process. PMID- 2234704 TI - Primary malignant melanoma of the uterine cervix: two case reports and a century's review. AB - Primary malignant cervical melanoma is diagnosed by the presence of junctional melanocytic abnormality and the absence of distant metastasis. Amelanotic and poorly differentiated tumors can often be diagnosed with the HMB-45 immunoperoxidase stain which is very specific for melanoma. Early reported cases were treated with simple excision followed many times by radiation therapy. Radical hysterectomy, pelvic lymphadenectomy, and partial vaginectomy have been advocated by some contemporary investigators. Radiation can be used as adjuvant or palliative treatment; its efficacy is not well established. Few patients have been treated with modern chemotherapy. No patient has been treated with immunotherapy. Primary malignant cervical melanoma carries a very poor prognosis. Most patients succumb from their disease within 2 years. One patient has survived 14 years. The small number of reported cases makes it difficult to evaluate the efficacy of any treatment modality. PMID- 2234705 TI - Pulmonary hypoplasia: a review. PMID- 2234706 TI - Classification of endometrial cells on cervical cytology. AB - One hundred eighty-eight women who had endometrial cells on cervical cytologic specimens during the secretory phase or in the postmenopausal period were studied retrospectively. Each had undergone hysterectomy or endometrial biopsy within 12 months of the original smear. The endometrial cells were classified as typical, atypical, or suspicious for carcinoma. Among premenopausal subjects, three of 57 with typical cells had endometrial hyperplasia, one of two with atypical cells had endometrial polyps, and both with cells suspicious for carcinoma had endometrial carcinoma. In the postmenopausal group, ten (13.5%) of 74 with typical endometrial cells had either hyperplasia or carcinoma, and five (22.7%) of 22 with atypical cells and 24 77.4%) of 31 patients with suspicious cells had either hyperplasia or carcinoma. The present findings and a review of the pertinent literature demonstrate that the classification system used is helpful in predicting the risk for endometrial disease in patients with endometrial cells seen on cervical cytologic smears during the secretory phase or in the postmenopausal period. PMID- 2234707 TI - Observer variability in the scoring of colpophotographs. AB - Colposcopy and cervicography are accepted tools for assessing the cervix for an atypical transformation zone. We studied the validity of the colpophotograph as a measurement tool by determining the agreement of experienced colposcopists using colpophotographs of 50 women. Interobserver agreement was generally fair to good (kappa greater than or equal to 0.40) for the presence of the squamocolumnar junction and the area of ectopia but it was poor (kappa less than 0.40) for the area, border, and color characteristics of an atypical transformation zone. Intra observer agreement was fair to good for the color characteristics of an atypical transformation zone, but it was poor for the area and border characteristics. We conclude that observer agreement studies should play a role in the validation of methods used in the visual diagnosis of cervical intraepithelial neoplasia. Considerable lack of agreement in reporting cytologic findings is a well-known problem, and lack of agreement might be an even bigger problem in reporting colposcopic findings. PMID- 2234708 TI - A randomized trial comparing two methods of cold knife conization with laser conization. AB - In a randomized study, 62 women were submitted to cold knife conization with application of Sturmdorf sutures, 60 to cold knife conization without sutures, and 61 to laser conization. Early hemorrhage occurred in 1.6, 13.3, and 6.6% of women, respectively (P less than .05), and late hemorrhage in 15.3, 3.6, and 11.7%, respectively. Considering early and late hemorrhage together, there was no significant difference among the three treatment groups. Dysmenorrhea tended to be more common after application of Sturmdorf sutures, as it was reported by 27.8, 13.2, and 14.3% of patients, respectively, but the difference was not statistically significant. Dysmenorrhea occurred in 13% of the cases with a cone height of 20 mm or less and in 26% of the cases with a cone height greater than 20 mm (P less than .05). Endocervical cells were present significantly more often after sampling with a cytobrush than with a cotton swab (P less than .0001), whereas the method of conization had no influence. In smears obtained with a cytobrush, endocervical cells were present in 88.0, 84.9, and 82.5% of the cases; in smears obtained with a cotton swab, endocervical cells were present in 46.6, 57.7, and 54.5%, respectively. We conclude that cold knife conization without Sturmdorf sutures is about equal to laser conization in overall complications, but the laser is preferable for outpatient treatment because of a lower frequency of early hemorrhage. Sturmdorf sutures should be avoided. Smears at follow-up should be taken with a cytobrush and a wooden spatula. PMID- 2234709 TI - Basement membrane of cervical adenocarcinoma: an immunoperoxidase study of laminin and type IV collagen. AB - The basement membrane components type IV collagen and laminin were examined immunohistochemically in 14 cases of adenocarcinoma of the cervix. The patterns of staining in adenocarcinoma in situ, invasive adenocarcinoma, and early invasive adenocarcinoma were compared to see whether characteristic patterns could be delineated. Adenocarcinoma in situ had a uniform intact basement membrane, whereas the basement membrane of invasive adenocarcinoma was fragmented and irregular. Cases of early stromal invasion showed early gland buds and outpouchings with defective basement membrane staining. The degree of histologic differentiation of the tumor was not clearly related to the amount of basement membrane component staining. The concept of early stromal invasion in cervical adenocarcinoma, as supported by our immunohistochemical studies, is discussed as it relates to a possible pathogenic mechanism in early invasion and infiltration of adenocarcinoma of the cervix. PMID- 2234710 TI - Treatment of fallopian tube carcinoma with cisplatin, doxorubicin, and cyclophosphamide. AB - Primary carcinoma of the fallopian tube is uncommon and is often treated using regimens active in ovarian carcinoma. Evidence is scant that such therapies benefit patients with fallopian tube carcinoma. Between December 1979 and July 1988, we treated 18 patients who had adenocarcinoma of the fallopian tube with the combination of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) administered intravenously on 1 day every 28 days. Histologic confirmation of fallopian tube carcinoma was obtained before entry in the study. Three patients had stage I disease, five had stage II, nine had stage III, and one had stage IV. Sixteen patients received the combination therapy as first-line treatment after cytoreductive surgery, and two patients received it for recurrent carcinoma. Seven patients had clinically measurable disease at the start of therapy. Two of these patients had a complete clinical response, two had stable disease, and three had progressive disease. Eight of the 15 patients with stages II-IV disease underwent second-look laparotomy; four had a complete response to therapy and four had a partial response, making the overall response rate 53%. The toxicity of the regimen was moderate. The median survival was 81 months. Patients with stages II-IV disease had a median survival of 43.9 months and a progression-free survival of 22.5 months. This regimen appears to be active in fallopian tube carcinoma and can result in response rates comparable to those reported for epithelial ovarian cancer. PMID- 2234711 TI - Early amniocentesis: report of 407 cases with neonatal follow-up. AB - Amniocentesis was performed for prenatal diagnosis in 407 pregnancies between the gestational ages of 11-14 weeks. The safety and accuracy of the procedure were compared with data obtained from collaborative studies of amniocentesis performed later in the second trimester. There were no differences observed with respect to accuracy, pseudomosaicism, or maternal-cell contamination related to the timing of the procedure. The fetal loss rate within 4 weeks of the procedure was 2.3%. Fetal losses appeared to be related to maternal complications such as bleeding and leakage of fluid that occurred within a day of the procedure. No major maternal complications were noted. Information regarding neonatal outcome, including pulmonary complications and congenital orthopedic postural deformities, was found to be similar to that in previous reports. PMID- 2234712 TI - Effect of maternal smoking and age on congenital anomalies. AB - The incidence of congenital anomalies was examined by the level of maternal and paternal smoking during pregnancy for 17,152 infants. A multiple regression analysis was used to control for the possible confounding effects of maternal age, formal education, ethnic origin, religion, marital status, parity, social class, and work outside the home. Neither maternal nor paternal smoking habits were significantly associated with the occurrence of congenital malformations. Maternal age was significantly (P less than .005) related to the incidence of major anomalies. Mothers aged 35 years and older who smoked were found to have a significantly (P less than .002) higher risk for minor malformations and a nonsignificantly increased rate of major malformations. Maternal cigarette smoking may be an important preventable risk factor for congenital anomalies among mothers aged 35 years or older. PMID- 2234713 TI - Maternal mortality in the United States, 1979-1986. AB - To understand better the epidemiology and to describe the causes of maternal death, we reviewed all identified maternal deaths in the United States and Puerto Rico for 1979-1986. The overall maternal mortality ratio for the period was 9.1 deaths per 100,000 live births. The ratios increased with age and were higher among women of black and other minority races than among white women for all age groups. The causes of death varied for different outcomes of pregnancy; pulmonary embolism was the leading cause of death after a live birth. Unmarried women had a higher risk of death than married women. The risk of death increased with increasing live-birth order, except for primiparas. In order to develop strategies to reduce the risk of maternal death in the United States, future studies should include expanded information about each death, which will allow better understanding of factors associated with maternal mortality. PMID- 2234714 TI - Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study. AB - Preeclampsia is a disease unique to pregnancy that contributes substantially to maternal and fetal morbidity and mortality. The condition has been thought to be one of hypoperfusion in which increased vascular resistance characterizes the associated hypertension. This study was designed to test an alternative hypothesis, that preeclampsia is characterized by high cardiac output. In a blinded longitudinal study of nulliparas with uncomplicated pregnancies, cardiac output was measured serially by Doppler technique. Cardiac output was elevated throughout pregnancy in patients who became preeclamptic (P = .006). Six weeks postpartum, the hypertension of the preeclamptic subjects had resolved but cardiac output remained elevated (P = .001) and peripheral resistance remained lower than in the normotensive subjects (P = .001). This study demonstrates that preeclampsia is not a disease of systemic hypoperfusion and challenges most current models of the disease based on that assumption. PMID- 2234715 TI - Aggressive or expectant management for patients with severe preeclampsia between 28-34 weeks' gestation: a randomized controlled trial. AB - Fifty-eight women with severe preeclampsia between 28-34 weeks' gestation qualified for a randomized controlled trial to establish whether elective delivery 48 hours after administration of betamethasone (aggressive-management group) or delivery later as indicated by maternal or fetal condition (expectant management group) was more beneficial to maternal and fetal outcome. Twenty women who qualified were not randomized because they developed maternal or fetal indications necessitating delivery within 48 hours; these newborns developed most of the complications. Expectant management was not associated with an increase in maternal complications, but it significantly prolonged the gestational age (mean 7.1 days; P less than .05), reduced the number of neonates requiring ventilation (P less than .05), and reduced the number of neonatal complications (P less than .05). PMID- 2234716 TI - Does indomethacin alter the hemodynamic response to magnesium sulfate infusion and hemorrhage in gravid ewes? AB - The purpose of this study was to determine whether indomethacin alters the maternal and fetal hemodynamic response to magnesium sulfate (MgSO4) infusion and hemorrhage in gravid ewes. We studied seven chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included: 1) at time 0, indomethacin, 2 mg/kg, or vehicle only intravenously (IV) over 5 minutes; 2) at 60 minutes, MgSO4 4 g IV over 5 minutes; 3) at 65 minutes, MgSO4 infusion at 4 g/hour; 4) at 150 minutes, maternal hemorrhage, 20 mL/kg, over 60 minutes; and 5) at 215 minutes, reinfusion of maternal blood over 60 minutes. Each animal was studied with and without indomethacin. Indomethacin, but not vehicle only, transiently increased maternal and fetal mean arterial pressure (MAP), decreased maternal and fetal heart rate, and decreased maternal cardiac output. Magnesium sulfate significantly decreased uterine vascular resistance and increased uterine blood flow both with and without indomethacin. Hemorrhage significantly decreased maternal MAP, heart rate, cardiac output, and uterine blood flow in both groups. The magnitude of each change was similar between the groups. For example, at the end of hemorrhage, maternal MAP was 36 +/- 7% below baseline (P = .0001) with indomethacin and 41 +/- 2% below baseline (P = .0001) in the vehicle-only group (P = not significant between groups). Hemorrhage significantly decreased fetal heart rate, pH, and PO2, and increased fetal MAP and PCO2 in both groups. We conclude that indomethacin did not alter the maternal or fetal hemodynamic response to MgSO4 infusion and hemorrhage in gravid ewes. PMID- 2234717 TI - Pregnancy and liver transplantation. AB - To define the risks and outcomes associated with pregnancy and liver transplantation, we reviewed our experience in managing eight pregnant women who had undergone orthotopic liver transplantation. Seven patients conceived after transplantation; the interval from transplantation to conception ranged from 3 weeks to 24 months. One patient received an allograft at 26 weeks' gestation for hepatic failure secondary to acute fulminant hepatitis B. Of the seven patients who conceived after transplantation, six had live births and one electively terminated her pregnancy. Five patients developed worsening hypertension and/or preeclampsia. Three patients developed severe preeclampsia and required delivery. One patient suffered acute allograft rejection during pregnancy which was successfully treated with corticosteroids. Two patients had persistent elevation of serum transaminases and two had severe anemia. The mean gestational age at delivery was 32.8 weeks. Of the six live births to women who conceived after transplantation, five infants survived and are well and one infant died. There were no congenital anomalies. All mothers are alive at this time. Pregnancy in recipients of hepatic allografts is associated with good perinatal outcome, but there is an increased risk of preeclampsia, worsening hypertension, and preterm delivery. Pregnancy does not appear to have a deleterious effect on hepatic graft function or survival. Joint management of these patients by a transplant specialist and a perinatologist is essential. PMID- 2234718 TI - Objective tocodynamometry identifies labor onset earlier than subjective maternal perception. AB - The ability of women instructed in self-detection of uterine contractions to identify the abrupt rise in uterine activity known to precede the onset of labor has not been evaluated. This study was designed to assess the temporal relationship between objective uterine activity monitoring, subjective maternal perception of uterine activity above a commonly used threshold value (four or more contractions per hour), and progressive cervical change. Daily tocodynamometry (7-9 AM) was recorded in 79 women with preterm premature rupture of the membranes from admission until the onset of spontaneous labor (5.3 +/- 6.3 days). The subjects were at bed rest, received no tocolytic therapy, and were instructed in the signs of labor and uterine self-palpation. Patients simultaneously provided a subjective assessment of uterine activity (four or more contractions per hour). The majority of uterine activity recordings (78%) revealed fewer than four contractions per hour, and the patients' subjective reports agreed in almost all instances (97.6%). On 91 days, four or more contractions per hour were recorded objectively, but the patients' subjective reports agreed in only 25 instances (27%). On the day of labor onset, significantly more women had an objective assessment (32%) (P less than or equal to .01). Patients subjectively identified labor onset 10.6 +/- 6.7 hours after objective monitoring indicated increased uterine activity, and when subjectively identified, both cervical dilatation (4.9 +/- 2.5 cm) and effacement (85 +/- 30%) were significantly advanced (P less than or equal to .001) compared with the admission examination (1.1 +/- 1.2 cm; 20 +/- 30%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2234720 TI - Doppler umbilical artery studies in the twin-twin transfusion syndrome. AB - Eleven patients with twin pregnancies were identified as having twin-twin transfusion syndrome on the basis of like-sex twins with monochorionic placentation and umbilical venous blood hemoglobin differences exceeding 50 g/L at delivery. Umbilical artery velocity-time waveform studies had been performed in these pregnancies as part of a large series of 456 twin pregnancies. In all 11 cases, the systolic-diastolic (S-D) ratio differences between the twins were less than 1 unit (mean 0.4 +/- 0.2), indicating that in twin-twin transfusion, umbilical artery S-D ratios are concordant even in the presence of discordancy in fetal size. PMID- 2234719 TI - Effect of angiotensin II infusion during normal pregnancy on flow velocity waveforms in the uteroplacental and umbilical circulations. AB - Women destined to develop preeclampsia show an increased systemic pressor response to infused angiotensin II, and the angiotensin sensitivity test has been accepted as an appropriate means of identifying these women. However, the effect of angiotensin II infusion on uteroplacental blood flow is unknown and may be deleterious. Patients undergoing angiotensin sensitivity tests as part of a protocol examining the effect of aspirin on the incidence of preeclampsia were studied with Doppler velocimetry performed before and during the angiotensin II infusion. Fetal well-being was documented with biophysical profiles performed before and after the infusions. Neither the systolic-diastolic ratios in the uterine and umbilical arteries nor the biophysical profile scores were altered significantly (P = .43, P = .23, Wilcoxon signed-rank median test, and P = .35, Fisher exact test, respectively). These findings suggest that the angiotensin sensitivity test does not increase resistance to flow in the uterine or umbilical circulation, and therefore may be used safely in screening for preeclampsia. PMID- 2234721 TI - The association between oligohydramnios and intrauterine growth retardation. AB - Among 147 cases of suspected intrauterine growth retardation (IUGR) identified based upon ultrasonic abdominal circumference below the tenth percentile, 56 were confirmed IUGR infants at birth and 91 were non-IUGR infants. Eight of 316 control fetuses with abdominal circumference above the tenth percentile turned out to be IUGR infants at birth. The incidence of oligohydramnios was strikingly different among the three groups: 29% for the IUGR group, 9% for the non-IUGR group, and 0.6% for the controls (P less than .001). When the criteria of abdominal circumference below the tenth percentile and presence of oligohydramnios were used together, the positive predictive value doubled (from 38.1 to 66.7%; P less than .01). Oligohydramnios developed some time after the somatic evidence of fetal growth retardation in all cases in this study. Finally, there were no significant differences between fetal growth retardation with or without oligohydramnios with respect to maternal risk factors or fetal outcome. We conclude that in fetal growth retardation, the occurrence of oligohydramnios during the third trimester of pregnancy is not associated with worse fetal outcome. PMID- 2234722 TI - Obstetric practice patterns in Washington state after tort reform: has the access problem been solved? AB - We surveyed all potential obstetric providers in Washington state in the spring of 1989 to determine whether the passage of tort reform in 1986 had improved access to care for rural and medically indigent women. We found that, although the exodus of family physicians from obstetric practice that had been observed between 1985-1986 appears to have slowed, there is still substantial net attrition among family physicians. As a result, rural patients are having increasing difficulty obtaining local access to obstetric care. By contrast, the supply of obstetricians and midwives seems to be stable. All three groups of providers are increasingly reluctant to provide care to the growing number of Medicaid patients. Although tort reform may have slowed the rate at which providers are quitting obstetrics, equilibrium has not yet been achieved. Shortages of rural physicians and inadequate Medicaid reimbursement rates must be addressed to improve obstetric access for underserved groups. PMID- 2234723 TI - Early age at menopause among left-handed women. AB - Associations have been suggested between handedness, autoimmune disorders, and reproductive hormonal changes. The purpose of this study was to test a proposed relationship between handedness and age at menopause. Two national survey data sets were used to compare recalled ages at menopause. Mexican-American women, ages 35-74, naturally postmenopausal for at least 1 year, were selected from the Hispanic Health and Nutrition Examination Survey (HHANES). White and black women were selected from the National Health and Nutrition Examination Survey (NHANES I) using similar criteria. The mean age at menopause was found to be earlier among left-handed women than right-handed women from the NHANES-I data set. In the HHANES data set, the mean age at menopause was significantly earlier among left-handed women than in right-handed women (t = 2.35, P less than .05). Early age at menopause among left-handed women may result from misclassification of handedness among older women or differential mortality among left-handed individuals. Alternatively, the association may be related to possible correlations between left-handedness and autoimmune disorders, which may include reactions against hormone receptor sites and oocytes. PMID- 2234724 TI - Whither electronic fetal monitoring? AB - Largely based on promising animal studies, continuous electronic fetal monitoring (EFM) was introduced into clinical practice in the early 1970s. After almost 20 years of experience, it is now apparent that the anticipated benefits of this technology have not materialized. Undesirable side effects of EFM include inappropriate operative intervention for some patients and increased liability for physicians and hospitals, resulting in an increase in the costs of obstetric services. After reviewing several research studies, The American College of Obstetricians and Gynecologists concluded that EFM and intermittent auscultation are equivalent methods for intrapartum assessment. We have developed a protocol for the performance of intermittent auscultation, including indicated responses to different levels of bradycardia. This protocol has allowed us to substitute auscultation for EFM in a high percentage of patients using existing nursing personnel. Laboring patients should, at a minimum, receive information on both intermittent auscultation and EFM to enable them to make an informed choice of method for intrapartum fetal assessment. PMID- 2234725 TI - Debulking of pelvic and para-aortic lymph node metastases in ovarian cancer with the cavitron ultrasonic surgical aspirator. AB - Six patients with metastatic ovarian cancer with extensive involvement of the pelvic and/or para-aortic lymph nodes underwent surgical debulking with the Cavitron Ultrasonic Surgical Aspirator. Intraoperative and postoperative morbidity was minimal. It is suggested that this technique may be used for cytoreductive surgery in combination with standard surgical techniques. PMID- 2234726 TI - Objective assessment of meconium content of amniotic fluid. AB - The amount of meconium in amniotic fluid is subjectively estimated by visual inspection and classified as thin (light), moderate, or thick (heavy). This estimate may be important for assessing the neonatal risk of perinatal asphyxia and meconium aspiration syndrome. This study reports on the "meconium-crit," a simple, rapid, inexpensive, and reproducible method of quantifying meconium concentration in amniotic fluid. The purpose of the study was to determine the relationship between the meconium-crit and meconium concentration. Specimens were prepared by placing 3.0 g of fresh neonatal meconium into clear amniotic fluid and vortexing for 15 minutes to obtain a stock solution of 15.0 g meconium/100 mL amniotic fluid. Stock solutions were then diluted with clear amniotic fluid to obtain concentrations of 10.0, 7.5, 5.0, 3.0, and 1.5 g/100 mL. One-tenth milliliter of the amniotic fluid/meconium mixture was drawn into a standard hematocrit tube and centrifuged. The meconium-crit was then measured directly as with a hematocrit. Regression analysis indicated that meconium-crit values were linearly related to meconium concentration (r = 0.901-0.995). This method provides a reproducible means of quantifying meconium in amniotic fluid. PMID- 2234727 TI - Terms of confinement. PMID- 2234728 TI - Complications of first-trimester abortion: a report of 170,000 cases. PMID- 2234729 TI - Oral contraceptives and breast cancer: a case-control study with hospital and community controls. PMID- 2234730 TI - Pregnancy outcome of patients with uncorrected uterine anomalies managed in a high-risk obstetric setting. PMID- 2234732 TI - Stress in life and work. Part 1: How it affects the individual. PMID- 2234731 TI - The significance of moderate and severe inflammation on class I Papanicolaou smear. AB - The significance of a cytologic diagnosis of moderate and severe inflammation with a normal (class I) Papanicolaou smear has not been addressed. A retrospective review of 596 consecutive cervical smears performed over 13 months revealed 85 women who had a class I cytologic smear with moderate to severe inflammation. Seventy-eight patients had colposcopic examinations and were considered for this study. Fifty-nine (75.6%) had cervical punch biopsies and/or endocervical biopsies. Of the 78, 19 (24.4%) had cervical condylomata and nine (11.5%) had cervical intraepithelial neoplasia. We conclude that class I cytologic smears with moderate to severe inflammation may be associated with findings of condylomata and cervical dysplasia. PMID- 2234733 TI - Does sex sell safety? PMID- 2234734 TI - The end justifies the means. PMID- 2234735 TI - Psychotherapy: a counselling success. PMID- 2234736 TI - Advising early retirement on medical grounds. PMID- 2234737 TI - Building inspection crucial part of effective asbestos management. PMID- 2234738 TI - Asbestos in place may present immeasurable risks in buildings. PMID- 2234739 TI - Asbestos warrants care, management but society must resist urge to panic. PMID- 2234740 TI - Respirator innovation. PMID- 2234741 TI - Industrial hygienists take the field with new gas-detection technology. PMID- 2234742 TI - Preventing employee drug abuse starts with firm policy, awareness. PMID- 2234743 TI - Menstrual cycle disorders. PMID- 2234744 TI - Characteristics and control of the normal menstrual cycle. AB - The most important activity during the follicular phase of the cycle is the secretion of gonadotropins, which control folliculogenesis and influence uterine proliferation. The dominant events of the periovulatory phase are the LH surge and ovulation. The significant change during the luteal phase is the production of a nutritive mucus by the endometrial glands in preparation for an embryonic blastocyst. The cardinal passage of the menstrual phase is the menstrual flow itself. These different events (and the metabolic processes that regulate them) have wide-ranging effects on the integrity of the body. As Havelock Ellis, the eminent English psychologist, stated at the turn of this century, "the omnipresent process of sex, as it is woven into the whole texture of our body, is the pattern of all the process of our life" (source unknown). The sweeping influences of the menstrual cycle illustrate the extent to which the process of reproduction is indeed woven into the whole of the human body. PMID- 2234745 TI - Clinical manifestations of hormonal changes in the menstrual cycle. AB - The human female reproductive cycle is the result of repeated interactions- giving positive and negative feedback--of pituitary gonadotropic hormones and ovarian sex steroid hormones. If any of the pituitary or ovarian hormones becomes tonically elevated or suppressed, ovulation will cease. The charge to the clinician in evaluating disorders of ovulation is to determine which hormone(s) is tonically elevated or suppressed. Sex steroid hormones exert effects on their target tissues that can be observed directly. These changes aid the clinician in evaluating disorders of ovulation and establishing which hormone(s) is tonically elevated or suppressed. Changes in thermoregulation can be detected by the basal body temperature record. Changes in the vagina can be detected by cytologic examination. Changes in the endometrium can be observed by obtaining a biopsy specimen for histologic examination. Premenstrual molimina suggest to the woman and her clinician that ovulation has occurred. Utilization of these changes in clinical practice aids the clinician in making a specific diagnosis of the cause of anovulation and in developing a treatment plan. Moreover, when the woman is aware of these clinical changes, it makes her a more involved participant in her health care. PMID- 2234746 TI - Systemic illness and menstrual dysfunction. AB - Menstrual dysfunction can be associated with a number of systemic illnesses. Whereas the effects of some diseases on the reproductive system are simply a result of the pathophysiology of the disorders, in other cases, temporary cessation of reproductive function conserves energy for other tasks related to survival and well being. PMID- 2234747 TI - Influence of the menstrual cycle on systemic diseases. AB - Physiological changes associated with the menstrual cycle influence the clinical course of some diseases such as bronchial asthma, allergies, anaphylaxis, epilepsy, migraine, dermatoses, and porphyria. Hormonal manipulation can be beneficial in some patients. PMID- 2234748 TI - Menorrhagia. AB - Excessive vaginal bleeding, or menorrhagia, is one of the most common presenting symptoms for gynecologic patients. Although this disorder has many possible etiologies, it is generally possible to approach its diagnosis and management in an orderly fashion. When evaluating the menorrhagic patient, it important to gear the work-up toward a differential diagnosis that includes pregnancy-related causes, hormonal problems, iatrogenic etiologies, mechanical intrauterine disorders, infections of the lower genital tract, and gynecologic cancers (PHIMIC). This differential approach can guide the types of historical data obtained from the patient, focus the physical examination, and alert the practitioner to the most appropriate laboratory and radiologic evaluation. Therapy can differ widely, depending on the cause of the bleeding. Most types of menorrhagia respond to medical therapy with oral contraceptives, oral synthetic estrogens or progestins, and long-acting intramuscular progestins or GnRH agonists. Surgical approaches, such as dilatation and curettage or hysterectomy, are less and less a first-line therapy; but innovative surgical techniques such as hysteroscopy and laparoscopic surgery are becoming increasingly important. With rapid, goal-directed diagnosis and specific therapy, the medical complications, anxiety, and discomfort suffered by the woman with menorrhagia can be alleviated quickly. PMID- 2234749 TI - Amenorrhea. AB - Amenorrhea, the lack of menstruation, is a gynecologic disorder that may arise from a variety of causes. If a logical and orderly schema is followed, the correct diagnosis and appropriate management plan can be formulated. PMID- 2234750 TI - Vaginal bleeding in childhood and adolescence. AB - Vaginal bleeding in early childhood, regardless of its duration and quantity, is always of clinical importance. This article discusses the examination of the child and adolescent and reviews the various causes of vaginal bleeding in these patient groups. PMID- 2234751 TI - Abnormal bleeding in the climacteric. AB - In the perimenopausal years, we encounter a situation where the normal diminution in reproductive capacity, with its resulting disruption of the normal menstrual hormonal pattern, coincides with a very real risk of pelvic pathology. Limitation in the ability to diagnose and to treat these patients conservatively has in the past resulted in a high rate of hysterectomy. With increased understanding of the normal physiology of this stage of transition and with improved diagnostic tools, we are now able to come to a definitive diagnosis in most patients. This ability to assure the diagnosis has made it much easier to counsel the patient confidently about the appropriate course of action. We will continue to encounter the problem of hysterectomy for bleeding with no histologic lesion being found. Although reviewers' letters may be considered an unnecessary thorn in the side, the improved practice that has resulted from these efforts gives strong support to their continued activities. We can have confidence that our treatment plan evolved in a logical manner and offers our patients a high probability of benefit at justifiable risk. PMID- 2234752 TI - Cyclic pelvic pain. AB - Cyclic pelvic pain is a common gynecologic problem caused by relatively few diseases, which usually can be diagnosed and remedied quickly. Some complaints reflect normal physiologic aspects of the menstrual cycle (mittelschmerz, menstrual awareness). Premenstrual syndrome can be diagnosed, but an effective and convenient treatment is lacking. Dysmenorrhea is the commonest source of cyclic pain, diagnosed by its characteristic history and rapid relief on administration of antiprostaglandin agents. Endometriosis is diagnosed surgically and best treated either surgically then, or medically by danazol or GnRH agonists. In contrast, adenomyosis is a problem commonly encountered in later life, and hysterectomy is usually needed for both definitive diagnosis and treatment. PMID- 2234753 TI - Pelvic pain and infections. AB - Infectious etiologies of both acute and chronic pelvic pain are common and may involve multiple organ systems. In the evaluation of the acute pain, it is important to remember that rapidity of diagnosis is important because of the possibility of significant morbidity and even death if a condition is not attended to rapidly. In recent years, laparoscopic evaluation of the pelvis has provided a better understanding of the pathophysiology of some of these infections, as well as possible therapeutic maneuvers. The evaluation of chronic pelvic pain requires a thorough attempt at careful diagnosis with minds open to the possibility that other organ systems besides the genital tract may be involved. Laparoscopy also may be an important diagnostic and therapeutic tool in the evaluation of the sequelae of pelvic inflammation leading to chronic pelvic pain. All therapeutic modalities that are instituted on the basis of the diagnostic evaluation must take into consideration that a strong emotional component is generally associated with chronic pelvic pain. Such components must be addressed in order to achieve the best possible results for the patient. PMID- 2234754 TI - Premenstrual syndrome: an update for the clinician. AB - Premenstrual syndrome is a complex disorder in which a variety of symptoms can occur in the luteal phase of the menstrual cycle. The symptoms should occur each cycle only from the time near ovulation to soon after the onset of menses. There should be at least 1 week in follicular phase that is symptom-free. Symptoms should be severe enough to significantly interfere with the ability of the patient to function within her normal lifestyle. Diagnosis is based on clinical information from prospective charting of symptoms. Up to 50 per cent of patients who think they have PMS really suffer from another type of mental illness, usually a depressive disorder. Laboratory tests are not generally helpful in the diagnosis. Treatment is based on the type(s) of symptom(s). Available treatments are reviewed with documentation of results from double-blind placebo-controlled experimental designs. The etiology of PMS is not known. However, there are good empiric therapies available that can help most PMS patients. PMID- 2234755 TI - Hypnosis modality defended. PMID- 2234756 TI - The difference between ethical and unethical "marketeering". Another big fish/little fish scenario? PMID- 2234757 TI - The National Practitioner Data Bank. PMID- 2234759 TI - Perceptions realigned. PMID- 2234758 TI - Beyond instructions for use: how to counsel your patients about their prescriptions. PMID- 2234760 TI - "How far should physicians go to facilitate a patient's death?". PMID- 2234761 TI - What you need to know about disposing of infectious waste. PMID- 2234762 TI - What is infectious waste (and how do I get rid of it?). PMID- 2234763 TI - The State Health Insurance Task Force: progress notes from OSMA representative Owen Johnson, MD. PMID- 2234765 TI - Job's syndrome (granulomatous disease variant). PMID- 2234764 TI - Failure to diagnose: a key element in malpractice. PMID- 2234767 TI - The "longer view" of health care. PMID- 2234766 TI - Skin cancer: a review with consideration of treatment options including Mohs micrographic surgery. AB - A review of basal and squamous cell carcinoma of the skin is presented with emphasis on treatment modalities. A series of 312 cases of skin cancer is presented in which Mohs micrographic surgery was the treatment. This technique is indicated for tumors that are 1) recurrent; 2) on anatomic sites with a high risk for recurrence; 3) of large size; 4) of aggressive histologic type; 5) incompletely excised; or 6) present on important functional or asthetic areas. PMID- 2234768 TI - Anabolic steroids and the Ohio State Medical Board. PMID- 2234769 TI - Medical students take a fantastic voyage. PMID- 2234770 TI - New crop of medical students is on the 'horizon'. PMID- 2234771 TI - Cancer hospital dream becomes reality. PMID- 2234772 TI - How to find your way through the yellow pages maze. PMID- 2234773 TI - They tell us medicine is changing. PMID- 2234774 TI - Janiceps twins. PMID- 2234775 TI - Contraceptive use and counseling before and after an abortion in Ohio, 1981 and 1986. PMID- 2234776 TI - Therapeutic aspects of low-risk breast cancer. AB - Attempts to treat patients suffering from metastasizing or primary operable breast cancer in a risk adapted fashion have always been dependent on the detection and clinically relevant ranking of prognostic parameters. Despite a variety of assumed prognostic parameters and description of prognostic indices no generally accepted definition of low or high risk breast cancer has been established as yet. Nevertheless, attempts have been successful to accomplish risk adapted treatment strategies that resulted in a substantial reduction in treatment related morbidity. Thus, replacement of surgical ablation procedures by drugs manipulating hormonal feedback regulation has yielded less side effects. Furthermore, new antiestrogens and antigestagens are aiming at a reduction in the rate and degree of toxicity. In addition, chemotherapy of metastasizing disease as well as adjuvant systemic therapy is being investigated with consideration of the concept of a maximum in efficacy and a minimum in toxicity. PMID- 2234777 TI - Ether lipids and derivatives as investigational anticancer drugs. A brief review. AB - There is considerable evidence that certain ether lipids represent a new class of antineoplastic agents. The activity of some of these structures is partially mediated through non-specific host resistance cells. In addition, more importantly, these ether lipids have been shown to be cytotoxic for cells from a wide variety of tumors and leukemias. The site of the cytotoxic action of ether lipids appears to be the cell membrane. They inhibit the biosynthesis of phosphatidylcholine as well as the activity of protein kinase C and might interfere with some growth factor receptors. Higher concentrations of some of these compounds are not compatible with the lipid bilayer matrix of the membrane. However, it remains uncertain whether or not these effects represent the only mechanisms for the cytotoxic action of this material. Further experiments elucidating the molecular mechanisms in the cytotoxicity of these compounds are necessary. In vivo a wide variety of mouse and rat tumors have been found to be sensitive to the therapeutic activity of ether lipids, with other tumor and leukemia models, however, being resistant to this material. Clinical phase I pilot trials have been completed, showing tumor response in a small number of patients treated, and 3 drugs are currently in phase II studies. Some of these ether lipids are preferentially cytotoxic to leukemic cells in comparison with normal bone marrow cells within a certain dose range. Thus, they are suitable for purging residual leukemic cells from remission bone marrow used for autologous bone marrow transplantation. A phase I/II study of autologous bone marrow transplantation in acute leukemia using bone marrow cells treated with ether lipids is in progress. PMID- 2234778 TI - [Postoperative adjuvant whole abdomen irradiation in ovarian cancer]. AB - Seventy-nine patients with ovarian carcinoma stage I-III postoperatively received a whole abdominal irradiation (median dose: 22.5 Gy) followed by pelvic boost irradiation (median pelvic dose: 45 Gy) as the sole adjuvant therapy. Surgery preceding the irradiation was radical only in 59 percent of the patients. Whole abdominal irradiation was performed either in the moving-strip-technique or the open-field-technique. The median follow-up time was 57 months. The overall and the progression-free five-year survival rate of the whole group is 66 +/- 6% and 63 +/- 6%, respectively. We have not seen a clear-cut dependence of the survival rates on the completeness of the surgery, on tumor histology or grading. In a statistically significant way, the survival rates depend on the stage, the presence of tumor rests, and, above all, on the risk group. The overall five-year survival rate for the intermediate-risk patients is 78 +/- 7% and 22 +/- 11% for high risk patients. There aren't any randomized studies concerning the optimal adjuvant therapy for intermediate-risk patients. Because of the reproduceable results and the infrequent toxicity, whole abdominal irradiation seems to be a treatment equivalent to other adjuvant therapies for these patients. PMID- 2234780 TI - High-dose epirubicin in combination with cyclophosphamide (HD-EC) in advanced breast cancer: final results of a dose finding study and phase II trial. AB - In the dose finding study we were able to demonstrate that an increase of the epirubicin dose to 120 mg/m2 in combination with cyclophosphamide (600 mg/m2) is possible. The phase II trial had to check the efficacy and the toxicity of this combination with a therapy interval of 21 days. 34 patients with metastatic breast cancer previously not treated with chemotherapy for metastatic disease entered this phase II trial, which tested the efficacy and toxicity of the chemotherapy combination epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 (HD EC regimen) i.v. every three weeks. Excluded from the trial were patients at risk of anthracycline toxicity and those with bone or brain metastases. Results compare favourably with best data reported in the literature for chemotherapy of metastatic breast cancer: overall remission rates of 73% (35% CR, 38% PR), median TTP of 58 weeks for CR (range 32-168 weeks) and 52 weeks for the PR group (range 24-110 weeks); median survival time for CR 71+ weeks (range 52-196+), for PR 74+ weeks (range 40-134+ weeks). No therapy was given for remission maintenance after a stable remission was obtained. This results in a very favourable ratio of time with chemotherapy to maintenance time without chemotherapy, which is 10 weeks/62 weeks for CR and 12 weeks/49 weeks for PR. Evidence of tumor remission was found in 80% of the patients who already responded to chemotherapy after the first cycle. The early onset of tumor response as well as the short induction chemotherapy period necessary to obtain best response are considered major advantages of the HD-EC regimen. PMID- 2234779 TI - [Vaginal ultrasound as a screening method for detection of adnexa tumors in postmenopause?]. AB - 424 ovaries of 212 postmenopausal women not on hormone treatment were examined by vaginal ultrasound. 155 patients had no clinical complaints, 57 patients showed atypical uterine bleeding. 48 pathological findings could be detected sonographically (11.3%). Among the histologically clarified cases were 2 asymptomatic ovarian cancers. Altogether, the vaginosonography proved to be a very simple and effective method to detect ovarian tumors in postmenopausal women. PMID- 2234782 TI - [Dialysability of cytostatic drugs. Experimental studies in vitro]. AB - There are no established guidelines for detoxification for most cases of overdosage or intoxication with cytostatic drugs. Little is known about the dialysability of cytostatic drugs. To obtain further information on the dialysability of cytostatic drugs, human plasma was incubated with cytostatic drugs and dialysed in vitro using "mini-modules" with capillaries identical to clinical use. Cytotoxicity before and after dialysis was measured in a biological test system using permanent human lymphoblast cultures (LS2). The 20 cytostatic drugs studied could be categorised as follows: Good dialysability in vitro: methotrexate, 5-fluorouracil, cytarabine, actinomycin D, mitomycin C, 4-OH cyclophosphamide, ifosfamide, melphalan, dacarbazine, cisplatin. Intermediate dialysability in vitro: adriamycin, epirubicin, carmustine. Ineffective dialysability in vitro: daunorubicin, vincristine, vinblastine, vindesine, etoposide, teniposide, mitoxantrone. These in vitro results cannot be transferred automatically into the in vivo situation because of specific drug distribution and metabolic rates. Considering pharmacokinetic data, the following recommendations can be made for practical clinical purposes: Detoxification by hemodialysis in vivo: Possibly effective: Methotrexate, 5-fluorouracil, mytomicin C, cyclophosphamide, ifosfamide, melphalan, carmustine, dacarbazine. Ineffective: Adriamycin, epirubicin, daunorubicin, mitoxantrone, actinomycin D, etoposide, teniposide, vincristine, vinblastine, vindesine, cytarabine, cisplatin. PMID- 2234781 TI - Results and prognosis of acute non-lymphocytic leukemia in adults. A retrospective study of 319 patients between 1977-1987. AB - Between 1977-87, 319 patients with AML were admitted to Hannover Medical School. At all 41 of these patients were not treated (median duration of survival 0.6 months). Among the 278 treated patients, there was a CR rate of 53.6%, the median duration of remission was 10.1 months and the median duration of survival 7.0 months. The patients with FAB-classification M4-M5 had a worse prognosis than those with M1-M3. Patients under 50 years of age had a significant higher remission rate and survival time than those over 50 years. In the last 10 years, the remission rate rose from 37.3% to 61.0% (p = 0.1776). There was a rise in median duration of survival from 5.9 months (1977-79) to 8.0 months (1984-85) (p less than 0.001). The median remission time decreased from 15.8 months (1977-79) to 12.0 months (1984-85) (p less than 0.001). After the first reinduction therapy, the remission rate (46.6%), duration of remission (5.3 months), and duration of survival (4.1 months) was lower than after primary therapy. After the second reinduction therapy the CR rate was 69.2%, and the remission time 2.9 months. The CR rate after the third reinduction therapy was 22.2%. PMID- 2234783 TI - Cytotoxic activity of lysophosphatidylcholine analogues on human lymphoma Raji cells. AB - The cytotoxic activity of 21 lysophosphocholine analogues was tested on human lymphoma Raji cells. Structure-activity investigations revealed a more than 50 fold difference in the cytotoxicity between the different compounds. Whereas acyllysophosphocholines showed only borderline effects, the most pronounced toxic activity was observed with compounds which have an etherbond in the sn-1 position and a hydrogen, a methoxy or a methoxymethylgroup in position sn-2. Elongation of the phosphorous-nitrogen distance in the choline group markedly reduced the cytotoxicity of the compounds. From the results obtained it was concluded that a long chain fatty alcohol adjacent to a phosphocholine headgroup represents the minimal requirement for antineoplastic activity. Thus, a new group of antineoplastic compounds, the alkylphosphocholines, was developed in our laboratory, with in vitro cytotoxic activities just as effective as the most toxic alkyllysophosphocholines. PMID- 2234784 TI - Characterization of human glioblastoma cell lines in vitro and their xenografts in nude mice by DNA fingerprinting. AB - Human gliomas were grown as permanent tissue cultures and xenografts in nude mice. DNA fingerprint patterns from two human gliomas were established using two different hypervariable multilocus probes [( GTG]5 and 33.15). In general the cell lines investigated showed an overall stability in the DNA fingerprint pattern. However, differences in the DNA fingerprint patterns were shown to occur depending upon the above mentioned parameters. PMID- 2234785 TI - [Cisplatin, vindesine and hyaluronidase combined with simultaneous radiotherapy of advanced head and neck tumors]. AB - In a prospective pilot study 21 patients with advanced squamous cell carcinoma of the head and neck were treated with polychemotherapy and Hyaluronidase combined with radiation. With the exception of one patient, who refused laryngectomy, all patients were inoperable. Chemotherapy consisted of 5 mg Vindesine on day 1 and 80 mg/m2 Cisplatin on day 2. 200,000 U Hyaluronidase were given by infusion over 20 min prior to Vindesine and Cisplatin. Radiation in fractions of 2 Gy a day was administered 12 times per cycle (day 3-5, 8-12 and 15-18). Treatment was repeated on day 22 and 43. Total radiation dose was 72 Gy. Side-effects were mainly of local character (moderate severe mucositis in 7, mild mucositis in 14 patients). No severe systemic toxicity was seen. Complete remission was noted in 17 out of 21 patients. 16 patients are now a life without progression. 1 patient in complete remission died 5 months after therapy due to pneumonia without evidence of tumor. The mean time of follow up is 16 months (range 3-42). The preliminary results suggest that combined therapy with Vindesine, Cisplatin, Hyaluronidase and Radiation is well tolerable and highly effective against advanced squamous cell carcinoma of the head and neck. PMID- 2234786 TI - [Requirements in clinical evaluation of drugs in oncology. Guidelines of the phase I/II study group of the Professional Society of Internal Oncology of the German Cancer Society]. PMID- 2234787 TI - [The role of the myoblasts and connective tissue in the regeneration of the limbs in amphibians]. AB - A possibility of tissue metaplasia (transformation of one cell type into another) during limb regeneration in lower vertebrates has been a matter of vivid arguments over the last decades. These discussions are rather irreconcilable in character mainly due to the lack of reliable cell markers which permit to follow all the stages of cell transformation during metaplasia. The final conclusions can be made only if any artifacts of cell labelling are excluded. Latest findings obtained using nuclear and cytoplasmic markers are presented which suggest that many data interpreted previously as a convincing proof of metaplasia may be a consequence of the involvement of nondifferentiated cells in regeneration. Molecular biological approaches are believed to be most promising for the solution of disputable problems of tissue metaplasia. However, recent findings about actin gene hypomethylation are insufficient for any final conclusions about the possibility of metaplasia during limb regeneration. The answer to many unsolved questions of developmental biology can be made only when combined use is made of modern methods of cell and molecular biology. PMID- 2234788 TI - [The molecular factors of the cell adhesion of neural tissues and the Ca2+ independent adhesion system]. AB - The review discusses various technical approaches to identification of plasma membrane and extracellular matrix proteins involved in cell adhesion. Physicochemical characteristics of macromolecular factors of the Ca2(+) independent adhesion system in neural tissue cells are discussed alongside with the findings on their biosynthesis and expression on the cell surface at different stages of embryogenesis. PMID- 2234789 TI - [Changes in the activity of different classes of enzymes in the cerebral cortex of rats in ontogeny and after the transplantation of embryonic nerve tissue]. AB - The activity of lactate dehydrogenase (LDH), indophenol oxidase, aspartate aminotransferase (AsAT), alkaline phosphatase, acid phosphatase and aldolase at different stages of rat development was measured. We have also determined changes in the activity of these enzymes resulting from transplantation of embryonic nerve tissue (ENT) into the brain of adult animals. During development from the embryo to the adult animal, LDH and AsAT activities increased, while alkaline phosphatase activity diminished. After ENT transplantation, the most prominent changes were in the alkaline phosphatase activity whereas the activity of LDH, AsAT and acid phosphatase remained unchanged and similar to that in the brain cortex of intact adult animals. Changes in the enzyme activity resulting from ENT transplantation changed in a manner characteristic of the transplant. Local brain damage did not change the activity of the studied enzymes fifty days after surgery. PMID- 2234790 TI - [Astrocyte death in organotypic cultures of fetal spinal cord from rats with unilateral micromelia]. AB - Growth and differentiation of neurons and glia in spinal cord explants of 16 days old rat fetuses with teratogen-induced left-sided micromelia were studied. Progressive destruction of astrocytes that differentiate in interstitial zone of cultures was observed in 37% of explants of the left side, while the development was normal in cultures of the right side. Possible mechanisms leading to destruction of astrocytes in cultures of spinal cord regions that innervate anomalous limbs are discussed. PMID- 2234792 TI - [The ultrastructure of the neurons of a graft developing in the brain of rats experiencing hypoxia]. AB - Fragments of the brain cortex of 17- or 18-day-old rat embryos were allotransplanted into the brain cortex of rats subjected to hypoxia. Four days later the graft consisted of mixed differentiating neuroblasts. By the 100th to 130th day after transplantation the graft contained mature neurons, differentiating neurons and neuroblasts. Hypochromic neurons showing the signs of intracellular reparation were also detected. A well-developed neuropile was localized inside the graft. In contrast to the normal brain, neurons in the graft were not organized in layers. PMID- 2234791 TI - [The differentiation of the nerve and glial cells of neocortical transplants placed into the brain of adult rats]. AB - Embryonal neural tissue of 17-day-old rat embryos was transplanted into the brain of adult Wistar rats to test the differentiation of transplants with reference to the normal cerebral cortex development. The control and the experimental rats were decapitated 2, 5, 7, 10, 15, 20, 25, and 35 days after the transplantation. Differentiation of neural tissue was studied using monoclonal antibodies against neurofilaments as well as by counting the proportion of differentiated neurons. The glial differentiation was studied by immunohistochemical method using monoclonal antibodies against acid glial fibrillar protein and vimentin. The differentiation of neural cells of transplants proved to be synchronous with the normal ones while the differentiation of glial cells accelerates. PMID- 2234793 TI - [Fibronectin distribution during the transdifferentiation and proliferation of eye cells after retinal detachment and removal of the crystalline lens in tritons]. AB - Expression of fibronectin (Fn) during eye tissue regeneration in the newt after retinal detachment and lens removal was studied by immunohistochemistry. Proliferation of cells involved in eye tissue regeneration was studied using autoradiography. Fn was detected around the cell membranes of undifferentiated proliferating and migrating cells in ciliary body of the iris and growth zone of the retina. Redistribution of Fn was observed in proliferating cells of the dorsal iris participating in lens regeneration. Fn appeared on the apical surface of proliferating redifferentiating pigment epithelium (PE) cells at the periphery of the eye and over the whole surface of proliferating PE cells in the central part of the eye. The Fn level in the Bruch's membrane decreased in the area of transdifferentiating cells detachment from PE layer (in the lower part of the eye) but continued to be stable in the area of PE cell redifferentiation (at the periphery of the eye). The role of Fn is discussed in relation to transdifferentiation, proliferation and migration of cells in the regenerating eye. PMID- 2234794 TI - [The capacity for regeneration of the myocardium in rat fetuses]. AB - A reproducible model of heart injury in 16-days old rat fetuses has been developed. 30 days after the injury a 4-fold increase of the damaged area was observed. Decrease of reparative capacity of myocardium in fetuses as compared with the adults is due to the functional immaturity of the connective tissue cells. PMID- 2234796 TI - [The parthenogenetic activation under the action of cycloheximide of mouse oocytes matured in vivo]. AB - Treatment of mouse oocytes matured in vivo by cycloheximide at a concentration 25 micrograms/ml for 2 h induced female pronucleus formation. In all activated oocytes the formation of the female nucleus was completed 5-6 h after the beginning of cycloheximide treatment. When cycloheximide concentration was decreased down to 5 micrograms/ml, its effect was detected 1 h later as compared with that at a concentration of 25 micrograms/ml. PMID- 2234795 TI - [The enzymes of fructose metabolism in the liver of chick embryos]. AB - The activity of fructose cycle enzymes remains practically constant in chick embryonic liver during ontogenesis. Change in ratio of aldolase A to B activities was detected. It is suggested that fructose enters the cycle via the sorbitol pathway in which aldose reductase and sorbitol dehydrogenase are involved. PMID- 2234797 TI - [Sexual dimorphism in the development of the neuronal populations of tractus solitarius nuclei in rats]. AB - Using light microscopy, we performed morphometric analysis of various cell populations of brain solitary tract nuclei at various stages of ontogenesis in rats. Sex-related dimorphism of development was observed in eight neuronal populations. Sex-related differences in the structure of these neurons persist in adult rats. The data obtained suggest that solitary tract nuclei participate in brain sexual differentiation. PMID- 2234799 TI - Laser madness in medicine. PMID- 2234798 TI - [Positional information and finger growth in man]. PMID- 2234800 TI - Overnight admission of outpatient strabismus patients. AB - The trend to outpatient strabismus surgery prompted us to determine the frequency of, and the reasons for, postoperative overnight hospital admission following such surgery. In one year, 303 outpatient strabotomies were performed at the Jules Stein Eye Institute on patients over 15 months old. Twenty-four (7.9%) were admitted overnight postoperatively. Compared with controls, those admitted were older (37 vs 20.5 years), and had a longer duration of anesthesia (145 vs 116 minutes) and surgery (104 vs 75 minutes) (P less than .01 for each). The time that surgery commenced and the use of perioperative medications were not significant factors. The most frequent reasons for overnight admission were nausea (38%) despite prophylaxis and the use of bilateral patches (16%). To minimize postoperative admissions, better strategies should be developed to decrease the frequency of significant postoperative nausea, the duration of surgery and anesthesia, and, if possible, the use of bilateral patches. PMID- 2234801 TI - Vitreous changes and macular edema in central retinal vein occlusion. AB - The condition of the posterior vitreous was determined in 56 eyes with central retinal vein occlusion (CRVO). Using a life-table analysis, it was studied in 56 eyes. The incidence of posterior vitreous detachment (PVD) in the CRVO eyes at the first vitreous examination did not differ significantly from that in 64 age matched control eyes. However, the incidence of PVD in CRVO eyes increased from 39.3% at the first vitreous examination to 58.5% after 6 months, and to 69.6% 1 year from the examination. The incidence of PVD in CRVO eyes during follow-up was statistically higher than that of the controls (P = .009). The incidence of PVD after the first vitreous examination was significantly higher in eyes with hemorrhagic retinopathy than in eyes with venous stasis retinopathy (P = .04). In the 34 eyes with macular edema, the edema lasted significantly longer in those with vitreomacular attachment (VMA) at the first examination than in those without VMA at this time (P = .02). VMA may play an important role in the pathogenesis and chronicity of macular edema in CRVO. PMID- 2234802 TI - Management of macular puckers associated with retinal angiomas. AB - Monocular visual loss in four patients was caused by epiretinal macular membranes associated with peripheral retinal capillary angiomas or angioma-like lesions. Three patients had solitary vascular lesions and one had two discrete vascular lesions. All patients were in good health, with no evidence of the von Hippel Lindau syndrome. In three patients, spontaneous peeling of the macular membranes and visual improvement occurred 2 to 6 months after obliteration of the angioma like lesions with cryotherapy (two patients), or cryotherapy combined with argon laser (one patient). The fourth patient underwent a vitrectomy 8 months after the macular pucker had failed to respond to treatment of the vascular lesion. PMID- 2234803 TI - Pupillary dilatation during cataract surgery--relative efficacy of indomethacin and flurbiprofen. AB - In a prospective, randomized, double-blind trial, we evaluated the relative efficacy of indomethacin and flurbiprofen when used as adjuvants to routinely used mydriatics for maintenance of pupillary dilatation in patients with heavily pigmented iris undergoing extracapsular cataract extraction. The drugs were administered orally as well as topically according to a fixed regimen. The pupillary diameters, measured with calipers at various surgical steps, were significantly larger at every step in the study groups in which either of the adjuvants had been used than they were in the control group (P less than .001). Flurbiprofen tended to help maintain a larger pupillary diameter in the later stages of surgery than indomethacin, but this difference was not statistically significant. We conclude that it is important to use prostaglandin synthetase inhibitors as adjuvants to routine mydriatics, and that flurbiprofen may be somewhat more effective than indomethacin in this capacity. PMID- 2234804 TI - Management of postoperative inflammation: dexamethasone versus flurbiprofen, a quantitative study using the new Flare Cell Meter. AB - A consecutive, random, prospective study was conducted to compare the effect of topical dexamethasone and flurbiprofen drops on postoperative inflammation in patients undergoing extracapsular cataract extraction with lens implantation. Objective, quantitative measurements were made postoperatively, using the Kowa FC 1000 Flare Cell Meter. The two treatments were equally effective. PMID- 2234805 TI - Retinal toxicity of intravitreal ticarcillin. AB - The retinal toxicity of the penicillin derivative, ticarcillin, was tested in albino rabbits by injecting the animals intravitreally with doses ranging from 50 to 3,000 micrograms, and monitoring them for 4 weeks. A second confirmatory study was performed by repeating the high-dose injections in a different set of rabbits and monitoring them for 3 weeks. Histologic examination and electroretinography of both groups showed that dosages up to 3000 micrograms produced no detectable damage to the retina. A dosage of 3000 micrograms of ticarcillin, which is 38 times the minimal inhibitory concentration for Pseudomonas aeruginosa, appears safe. PMID- 2234806 TI - Evaluation of peribulbar anesthesia in eye camps. AB - Modified peribulbar anesthesia was administered with a 26-gauge, half-inch, insulin needle to 367 eyes of 360 patients in three eye camps in India. The intraocular procedures consisted of cataract extraction in 349 eyes, trabeculectomy in 11 eyes, and combined cataract extraction and trabeculectomy in seven eyes. The overall success rate of the anesthesia technique was 90.2% (supplemental anesthesia was required in 36 eyes). There was good lid and globe akinesia and anesthesia, adequate pupillary dilatation for intracapsular cataract extraction, and excellent hypotony. No significant local or systemic complications were observed, except for mild to moderate chemosis in some eyes, which did not produce any intraoperative or postoperative problems. We found this technique easy to learn, relatively safe, effective, and well tolerated by our patients. PMID- 2234807 TI - Experience with photocoagulation in Behcet's disease. AB - Between 1973 and 1987 we examined both eyes of 300 patients with the uveoretinitis-type lesions characteristic of Behcet's disease. Of the 556 eyes whose fundus could be examined, 38 eyes (6.8%) in 33 patients (11%) had developed retinal capillary nonperfusion, branch retinal vein occlusion, or retinal or disc neovascularization. These eyes were treated by photocoagulation, primarily to forestall vitreous hemorrhage and the development of neovascular glaucoma, as well as to decrease the macular edema resulting from vein occlusion. The treatment, which was well tolerated, was successful in closing retinal capillary nonperfusion areas and eliminating retinal neovascularization. Disc neovascularization was resolved completely in some cases, and partially in others. PMID- 2234808 TI - Flexible endoscopy in primary dye testing of the lacrimal system. AB - The Olympus PF-22 angioscope was used to examine the inferior meatus during primary dye testing in 80 lacrimal systems in 48 patients. Dye testing was done bilaterally in 32 subjects with no known abnormalities of lacrimal excretory function; it also was performed on the apparently normal contralateral side of 16 patients with unilateral epiphora. Dye was observed in the nose in 79 of 80 lacrimal systems (99%). Dye was not observed in one patient, who appeared to have a dysfunctional lacrimal excretory system. Primary dye testing of the lacrimal system is reliable when the Olympus PF-22 angioscope is used to examine the inferior meatus. PMID- 2234809 TI - Increase of neuroretinal rim area after surgical intraocular pressure reduction. AB - The Optic Nerve Head Analyzer was used to measure the optic disc structure of 18 eyes (13 adult glaucoma patients) before and after surgical intraocular pressure reduction. Neuroretinal rim area markedly increased (from +0.15 mm2 to +0.45 mm2) in eight eyes, but changed either very little (less than +/- 0.1 mm2) or not at all in the remaining 10 eyes. The mean increase was from 0.75 +/- 0.26 mm2 to 0.92 +/- 0.36 mm2. The increased neuroretinal rim area found at this time remained in all eyes reexamined 1 to 3 years after surgery. Our data support previous findings that glaucomatous disc cupping may be reversed even in adult eyes, perhaps as the result of adequate pressure reduction. PMID- 2234811 TI - Monocanalicular intubation. PMID- 2234810 TI - Subconjunctival THC: YAG laser limbal sclerostomy Ab externo in the rabbit. AB - A chromium-sensitized, and thulium and holmium-doped YAG laser (THC:YAG laser) was used to create bilateral limbal sclerostomies in six Dutch pigmented rabbits. The laser is a long-pulsed (300 microseconds) [corrected], compact, self contained, solid-state laser operating in the near infrared (2.1 microns). A 1-mm conjunctival stab incision was made 12 mm away from the sclerostomy site to allow entry of a specially designed 26-gauge (480 microns) optic probe that delivers energy at right angles to the long axis of the fiber. Probe insertion minimally disturbed the conjunctiva. Pulse energies of 60 to 150 mJ were used with a repetition rate of 5 pulses/s. Energy levels ranging from 1.35 to 6.6 J produced full-thickness sclerostomies. Histopathology showed a sharply defined perforating limbal wound at all energy levels. The overlying conjunctiva was intact, with swelling of the adjacent cornea. A peripheral iridectomy was intentionally created with the laser through the peripheral limbus, resulting in a sharply defined perforating tract through the iris/ciliary body. This technique may simplify filtering sclerostomy surgery, without anterior chamber instrumentation and with minimal conjunctival trauma. PMID- 2234812 TI - Postkeratoplasty suture removal. PMID- 2234813 TI - In vivo intraocular lens failure. PMID- 2234814 TI - Polypropylene ligatures with Molteno implants. PMID- 2234815 TI - Evaluation of visual fields by ophthalmologists and by OCTOSMART program. AB - The introduction of Goldmann perimetry standardized measuring conditions as much as possible. In spite of this, it had been possible for the perimetrist to influence the results of perimeter measurements. The introduction of computer controlled perimetry, however, has largely eliminated the influence of the investigator on perimetry results. Nevertheless, the interpretation of a perimetric result in the everyday clinical situation is still extensively subjectively coloured and is liable to vary, depending on the doctor carrying it out. The OCTOPUS Program G1 was introduced a few years ago and used above all for glaucoma. This program greatly simplified visual field assessment thanks to its visual field indices. The indices make it possible to compare visual field results with those of a normal population. The present introduction of the OCTOSMART program represents a further step forward. This program analyses measured visual fields with the aid of standardized, statistical criteria based on a large, normal value study. This analysis standardizes and thereby simplifies the interpretation of visual field results. This study compares the outcome of the OCTOSMART program with visual field interpretations by eye doctors. PMID- 2234816 TI - Fluorescein angiography in ciliary body melanomas. AB - We retrospectively studied the value of iris fluorescein angiography in predicitng benignity or malignancy in 10 cases of ciliary body melanoma with iris extension. No correlation between fluorescein-angiographic appearance and histopathologic features was observed. Fluorescein angiography adds little to the management of ciliary body melanomas with iris extension. PMID- 2234817 TI - Argon versus krypton panretinal photocoagulation side effects on the anterior segment. AB - The modification of corneal sensitivity, accommodation, pupillary diameter and endothelial cell density after argon versus krypton panretinal photocoagulation were studied prospectively in 88 eyes of 64 diabetic patients with proliferative diabetic retinopathy, randomized for one of the two laser treatments. In both groups a marked internal ophthalmoplegia and reduction of corneal sensitivity occurred after laser photocoagulation. At no time, 2, 90 and 180 days after PRP, were these parameters significantly different. Endothelial cell loss was non significantly greater in the krypton group. The results indicated that the side effects commonly observed on the anterior segment after PRP are comparable using argon or krypton lasers. PMID- 2234818 TI - Central visual field changes after panretinal photocoagulation in proliferative diabetic retinopathy. AB - This study comprises 53 eyes, divided into two groups A and B, with proliferative diabetic retinopathy which were treated with panretinal photocoagulation (PRP). Its purpose is to investigate the alterations in the central 15 degrees and 30 degrees of the visual field and in each quadrant separately. In both groups A and B, PRP covered the periphery and mid-periphery. In group A, it stopped 2 disc diameters (DD) from the upper temporal and lower margin of the fovea including the papillomacular bundle, while in group B, PRP stopped 3 DD from the upper temporal and lower margin of the fovea and 1 DD of the nasal margin of the optic disc. The investigation revealed, in group B after PRP, an improvement of the retinal sensitivity in the central 15 degrees of the visual field (p less than 0.01). In the 30 degrees of the visual field a deterioration after PRP was noted in both groups A and B, the deterioration being however much more prominent in group A. Comparing the results between groups B and A after PRP, a difference in the retinal sensitivity in favour of group B at 15 degrees and 30 degrees of the visual field was found. As regards regression of neovascularization and visual acuity, no statistically significant difference has been observed between the two groups. PMID- 2234819 TI - Unusual exudative retinal detachment 9 months after scleral buckling surgery. AB - A 49-year-old man developed exudative retinal detachment 9 months after uncomplicated scleral buckling surgery in the left eye. The subretinal exudates were strictly localized along the buckle and showed remarkable response to steroid. The cause would be noninfectious inflammation like posterior scleritis, triggered by the buckle itself or its associated factors. It is important to note that subretinal exudates long after scleral buckling can occur in consequence of steroid-responsive inflammation as well as insidious bacterial or fungal infection described previously. PMID- 2234820 TI - Comparative study of different techniques of intraocular gas tamponade in the treatment of retinal detachment due to macular hole. AB - The injection of sulfur hexafluoride (SF6) or perfluoropropane (C3F8) was used as a method of internal tamponade in 43 eyes affected by retinal detachment due to macular hole. The technique of ocular hypotension prior to gas injection varied according to the characteristics of each case, using vitrectomy and SF6 30% in 8 cases (group 1), fluid-gas (SF6) exchange through the pars plana in 10 cases (group 2), paracentesis of the anterior chamber prior to injection of SF6 in 12 cases (group 3) and injection of C3F8 without drainage in 13 cases (group 4). Retinal reattachment was initially achieved in 87 (group 1), 83.3 (group 2), 100 (group 3) and 92.3% (group 4), but 4 recurrences yielded a 6-month follow-up cure of 75 (group 1), 75 (group 2), 91 (group 3) and 84% (group 4). Postoperative complications included proliferative vitreoretinopathy (7%), endophthalmitis (2.3%) and subretinal hemorrhage (2.3%). The use of intraocular gas tamponade appears to be a procedure with an acceptable complication rate in the treatment of retinal detachment due to macular hole. This study suggests the use of paracentesis and SF6 in phakic eyes, C3F8 in aphakic eyes and vitrectomy plus 30% SF6 in eyes with proliferative vitreoretinopathy or vitreoretinal traction adjacent to the macular hole. PMID- 2234821 TI - Visual disturbance in patients with melanocytoma of the optic disk. AB - Visual disturbance in 11 patients with melanocytoma of the optic disk was analyzed. Goldmann visual field examination showed enlargement of Mariotte's blind spot in 7 of 10 patients (70%) and visual field defect or depression in 7 patients (70%). In 6 of the 7 patients with visual field defect of depression (86%), the portion of visual field damage corresponded with the location of the tumor and retinal nerve fiber bundle defect. In 1 patient, sudden loss of visual acuity occurred, presumably due to anterior ischemic optic neuropathy induced by melanocytoma. PMID- 2234823 TI - Distance heterophoria and tonic vergence. AB - It has previously been suggested that the difference between tonic vergence (TV) and distance heterophoria may relate either to proximally induced vergence or accommodative divergence. To identify which of these components was responsible for this difference, the present study compared TV and distance heterophoria in a population of 20 subjects. However, distance heterophoria was now assessed with open-loop accommodation. No significant difference was observed between these two measures. This suggests that the previously observed variations between TV and distance heterophoria (with accommodation closed-loop) were produced by accommodative divergence. However, in a subgroup of 7 subjects, measurements of TV were more convergent (greater than 2 delta) than the distance heterophoria. In these subjects, proximally induced vergence may have accounted for the difference in response. PMID- 2234822 TI - Retinal sensitivity in acute hypoglycemia. AB - We measured retinal threshold sensitivity via automated computerized static perimetry in predetermined meridians in euglycemic diabetic subjects and in the same subjects during insulin-induced hypoglycemia. During periods of reduced blood glucose levels, decreased retinal sensitivity, most marked in temporal meridians, was observed. PMID- 2234824 TI - Changes in corneal thickness under four different rigid gas permeable contact lenses for daily wear. AB - The relation between corneal thickness changes and the Dk value of rigid contact lenses was investigated in 42 patients who were fitted with contact lenses for the first time. These 42 patients were divided into 4 groups that were fitted with contact lenses of different Dk values. Corneal thickness in the open-eye state was measured (mid-afternoon) before contact lens fitting and after 6 weeks of daily contact lens wear. The changes in corneal thickness were not significantly different among the 4 contact lens materials (Dk values 8, 26, 54, and 92). We conclude that for daily wear use the lower Dk materials meet corneal requirements. However, there is a significant trend; the higher Dk values result in a thinner cornea. Causes for this phenomenon are discussed. PMID- 2234825 TI - Clinician interpersonal communication skills and contact lens wearers' motivation, satisfaction, and compliance. AB - The relation between the practitioner and patient may have important effects upon the safety and success of contact lens wear. In this study we investigated the interrelations among clinicians' interpersonal communication skills and patients' motivation, satisfaction, and compliance with care and maintenance instructions. These variables were measured through questionnaires and interviews. Significant associations were found among many aspects of the clinicians' interpersonal skills and aspects of the patients' motivation and satisfaction. These findings are consistent with those from other health care settings and indicate that the quality of the contact lens practitioner's interpersonal skills can substantially influence patient outcomes and perceptions. PMID- 2234827 TI - A simple method for improving stereopsis. AB - Presented here is a method for the improvement of stereopsis. It is based on covering and uncovering one eye in a particular way. A complete program for the improvement of stereopsis is described. This includes an uncovering technique, the use of an Orthofuser, and the observation of specular reflections. Examples are given which demonstrate the effectiveness of the method. Persons who are capable of stereopsis but who use it selectively or not at all in everyday life (paradoxical stereopsis) are particularly easy to cure. PMID- 2234826 TI - Soft contact lens-induced longitudinal spherical aberration and its effect on contrast sensitivity. AB - Some investigators have suggested that the poor quality of vision which some spherical, single vision, soft lens-wearing patients report may be a result of spherical aberration induced in the ocular system when a soft lens is placed on the eye. In this study, the longitudinal spherical aberration of spherical soft lenses, both on and off the eye, was calculated using an aspheric corneal model and two-dimensional ray tracing program. Specifically designed front-surface aspheric, soft lenses were produced which demonstrated levels of in-air power variation similar to that calculated for similar-parameter spherically surface lenses. The effect of these lenses on the visual performance of nine subjects was assessed by measuring changes in contrast sensitivity and high contrast visual acuity through 3- and 6-mm artificial pupils. Significant losses of contrast sensitivity were recorded for the spherically aberrated lenses with the 6-mm pupil but not with the 3-mm pupil. High contrast acuity was not affected by any of the aberrated lenses with either the 3- or 6-mm pupils. Theoretical calculations and the contrast sensitivity results indicate that negatively powered lenses produce significantly less spherical aberration in situ than positively powered lenses. Because the majority of the prepresbyopic soft lens wearing population have low to moderate amounts of myopia, it would appear that soft lens-induced spherical aberration is unlikely to be responsible for the reduction in visual performance which some patients report when corrected with single vision soft lenses. PMID- 2234829 TI - Comparison of two clinical methods for measuring tonic accommodation in children. AB - Two methods have been described for measuring tonic accommodation (TA) under clinical conditions. One is the near retinoscopy (NEAR) method; the other uses Nott retinoscopy as the patient views a low spatial frequency difference of Gaussian (DOG) target. The purpose of this study was to compare the TA measures made by these two procedures on a group of 6- to 14-year-old children. The data indicate that the procedures yield significantly different information. PMID- 2234828 TI - Binocular inhibition: psychophysical and electrophysiological evidence. AB - Binocular summation, defined as an increase in the binocular response compared with the monocular, occurs when the sensitivities of the two eyes are equal. We investigated the psychophysical and electrophysiological binocular response to a difference in monocular retinal illuminance. Different levels of unequal monocular sensitivities were induced by means of neutral density filters placed in front of one eye. Both studies produced similar results. In the absence of filters, maximum binocular summation was produced. With increasing difference in monocular illuminance, the binocular response decreased steadily until it reached a level below the monocular. The clinical implications of binocular inhibition, a perceptual phenomenon similar to Fechner's Paradox, are discussed. PMID- 2234830 TI - Visual neural performance for chromatic displays. AB - Various subjective procedures have been used in the past to examine the visual disorders and ocular symptoms often associated with prolonged usage of Video Display Units (VDU's). We examined visual neural performance for VDU stimuli which differed in size (14, 21, or 28 min arc), chromaticity (white, red, green, or blue), and retinal clarity, by transient pattern visually evoked potentials (t p VEP's). Such information could prove useful in the design of electro-optical display systems that optimize visual neural performance and minimize ocular fatigue. Stimuli consisted of "monochromatic" (W, R, G, or Blue on black) and "multichromatic" (Blue/R, Blue/G, and R/G) checkerboards with brightness-matched chromatic elements displayed on a high resolution RGB monitor at 40 and 80 cm. The ambient lighting level was 54 lux. Group-averaged amplitudes and implicit times of t-p VEP's from 20 visually normal subjects indicated a differential neural response across target colors and three experimentally induced levels of blur. For monochromatic stimuli, the Blue/Black targets elicited t-p VEP's with the lowest amplitude, longest implicit time, and greatest sensitivity to optical defocus. Increasing the target element size reduced the VEP sensitivity to defocus across all colors except red. For multichromatic targets, Red/Green targets elicited the most vulnerable t-p VEP's. Several optical and neural explanations are given to explain these results. Implications for VDU designs are presented. PMID- 2234831 TI - Prevalence of Meibomian gland dysfunction. AB - This study was performed to determine the prevalence of Meibomian gland dysfunction (MGD) and to determine which patient profile factors might be associated with the syndrome. Patients were randomly selected, apparently normal patients presenting for routine vision examinations. Of the 398 patients for whom Meibomian gland expression was performed and a detailed history obtained, 155 patients or 38.9% exhibited MGD based on the principal clinical criterion of an absent or cloudy Meibomian gland secretion upon expression. Patient profile factors of gender, age, allergy occurrence, and contact lens wear were analyzed for correlation with MGD. Age was found to be the only significant correlating factor (positive correlation, p less than 0.0001). PMID- 2234832 TI - Visual acuity assessment from birth to three years using the acuity card procedure: cross-sectional and longitudinal samples. AB - We used the Teller Acuity Cards (TAC) to test 7 groups of 20 healthy infants and children ranging in age from 1 week to 36 months. We also tested 27 of these children at least twice within their first year. We had two primary goals: (1) to provide normative data on the development of visual acuity as assessed with the new version of the TAC (Vistech, Inc.) and (2) to investigate the predictive value of the TAC. The results from the cross-sectional samples show that our estimates of visual acuity are consistent with those reported by other researchers who used earlier versions of the TAC. The longitudinal data indicate that, on the average, an early estimate of visual acuity was not predictive of a later estimate, at least within the first year. The results are discussed in terms of the usefulness of the TAC for testing normal and clinical populations. PMID- 2234833 TI - Current methods of treating and preventing myopia. AB - In this review, we discuss and compare current methods of treating and preventing myopia including radial keratotomy, keratomileusis, keratophakia, epikeratoplasty, keratokyphosis, scleral reinforcement, phakoemulsification, and heat application. Among the visual training methods are such procedures as biofeedback and behavior modification. The use of drugs, orthokeratology, spectacles, bifocals, prisms, intraocular lenses, contact lenses, and ultrasound are described. PMID- 2234834 TI - Observations relating to paradoxical stereopsis. PMID- 2234835 TI - A possible reason for the lack of symptoms in aged eyes with low tear stability. PMID- 2234836 TI - Toxic ulcerative keratopathy. PMID- 2234837 TI - Penetrating keratoplasty in the management of posterior amorphous corneal dystrophy. PMID- 2234838 TI - More about advertising. PMID- 2234839 TI - Paying bounty for patients. PMID- 2234840 TI - Argon green (514 nm) versus krypton red (647 nm) modified grid laser photocoagulation for diffuse diabetic macular edema. AB - Between 1984 and 1988, 225 eyes of 132 patients were entered in a prospective, randomized clinical trial to determine if any significant differences exist between treatment with argon green (514 nm) and krypton red (647 nm) modified grid laser photocoagulation for patients with diffuse diabetic maculopathy with or without cystoid macular edema. At the 12- and 24-month follow-up visits, no statistically significant difference was found between the two groups with respect to all of the following: reduction or elimination of macular edema, improvement in visual acuity, worsening of visual acuity, number of treatments per eye, and effect on the visual field. At the 12-month follow-up visit, none of the following factors statistically affected the visual outcome in either of the two groups: a history of systemic hypertension, systemic vascular disease, cystoid macular edema, or initial poor visual acuity. PMID- 2234841 TI - Intraoperative massive suprachoroidal hemorrhage during pars plana vitrectomy. AB - Seven eyes (7 patients) developed massive suprachoroidal hemorrhage (MSCH) during pars plana vitrectomy (PPV) for complicated retinal detachments. The MSCH developed late in the procedure following PPV, air fluid exchange, endolaser, cryopexy, and scleral buckling in five of seven eyes. In two eyes, mild hemorrhagic choroidal detachments noted intraoperatively progressed to MSCH within 72 hours postoperatively. Diagnosis of MSCH was confirmed by echography and CT scan. Multiple scleral buckling surgeries, high myopia, aphakia, and intraocular inflammation were the main risk factors. Placement of a broad posterior scleral buckle with intraoperative hypotony and cryopexy were important precipitating factors. Visual results were poor, with six of seven eyes showing no light perception. The mean follow-up time was 12.8 months. Once acute MSCH is recognized intraoperatively, surgical decompression at that time should be avoided as MSCH itself may tamponade the choroidal bleed. Details of prevention and management are discussed. PMID- 2234842 TI - Autosomal dominant neovascular inflammatory vitreoretinopathy. AB - Twenty-eight of 61 members of a six-generation family are affected by an autosomal dominant eye disease which has not been described previously. Affected patients are asymptomatic in early adulthood, but have vitreous cells and the selective loss of the b-wave on the electroretinogram. Later, peripheral retinal scarring and pigmentation, peripheral arteriolar closure, and neovascularization of the peripheral retina at the ora serrata or occasionally neovascularization of the optic disc develop. Cystoid macular edema, vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma can cause profound visual loss. Vitrectomy reduces traction on the retina and allows for retinal reattachment. The role of argon laser photocoagulation or cryopexy in reducing the neovascular complications remains uncertain. PMID- 2234843 TI - HLA associations and ancestry in Vogt-Koyanagi-Harada disease and sympathetic ophthalmia. AB - A strong association with HLA antigens DR4, DRw53, and Bw54 has previously been reported among Japanese patients with Vogt-Koyanagi-Harada disease (VKH) and sympathetic ophthalmia (SO). In the United States, no firm association between HLA-A or -B loci and VKH has been found previously; testing for HLA-DR loci has not been performed to date. The authors performed HLA typing of 23 American patients with VKH and 8 patients with SO. When VKH patients were compared with racially matched controls without disease and patients with other types of uveitis, strong associations with HLA-DR4 and HLA-DRw53 were found. The strongest associations observed in this sample were with HLA-DQw3, an antigen which is in positive linkage disequilibrium with DR4, and with the HLA-DR4/DQw3 haplotype. The small number of patients with SO precluded statistical analysis; however, similar HLA associations were noted. The patients also were questioned regarding their ancestry. The anecdotal association of VKH with American Indian ancestry was confirmed. It appears that the ethnoracial association may be explained by HLA type. One possible explanation for identical HLA associations in two diseases with different precipitating events yet similar ocular manifestations is development of an altered immune response to exogenous microbial antigen with subsequent autoimmunity. Further definition of the genetic susceptibility to VKH and SO may help define the pathophysiology of both diseases and allow the prediction of which patients are at increased risk for SO. PMID- 2234844 TI - The epidemiology of ophthalmic malignancies in New York State. AB - The epidemiologic characteristics of more than 1400 primary eye cancers (ICD-9, site 190) diagnosed among New York State (NYS) residents between 1975 and 1986 are described. Among NYS male residents, the average annual age-adjusted incidence rate was 7.5 per 1,000,000, and among NYS female residents, the rate was 5.4 per 1,000,000 (male:female rate ratio, 1.39). The majority of ophthalmic malignancies were included within three histologic groupings: melanomas (70.4%), retinoblastomas (9.8%), and squamous cell carcinomas (9.2%). The average annual incidence of retinoblastoma among persons in NYS who were less than 5 years of age was 9.5 per 1,000,000 for boys and 8.7 per 1,000,000 for girls (male:female rate ratio, 1.09). The average annual incidence (age-adjusted) of ocular melanomas was 4.9 per 1,000,000 among men and 3.7 per 1,000,000 among women in NYS (male:female rate ratio, 1.32). Expanded knowledge of the epidemiology of ophthalmic cancers can help to develop a foundation on which to monitor disease patterns and can serve to stimulate further etiologic research involving these rare malignancies. PMID- 2234845 TI - Acquired retinal arteriovenous communications in occlusive disease of the carotid artery. AB - Retinal arteriovenous communications proximal to extensive areas of complete vascular closure developed in three patients with occlusive disease of the carotid arteries. In one case, the authors document the development of the arteriovenous communications through successive enlargement of small retinal vessels after progressive signs of retinal ischemia in the form of narrowed retinal arteries, venous dilation and beading, microaneurysms, retinal dot and blot hemorrhages, cotton-wool spots, and capillary nonperfusion. The development of arteriovenous communications in carotid occlusive disease has not been described previously. PMID- 2234846 TI - Serum and aqueous humor sialic acid levels in Behcet's disease. AB - Serum and aqueous humor sialic acid (SA) levels were determined in 27 patients with Behcet's disease (Bd). Serum SA levels were elevated significantly during the active episode (mean, 113.4 +/- 4.12 mg/dl) and in the remission stages (mean, 85.4 +/- 4.79 mg/dl; P less than 0.001). A significant increase was also detected in active episodes when compared to chronic stages (P less than 0.02). Aqueous humor levels were also evaluated but could only be determined in the six eyes at the end-stage of the disease (mean, 2.65 +/- 0.60 mg/dl; P less than 0.05). PMID- 2234847 TI - Clinical spectrum of leber's congenital amaurosis in the second to fourth decades of life. AB - Leber's congenital amaurosis is a type of congenital retinitis pigmentosa in which the fundus abnormalities are extremely variable and to some extent age dependent. Most cases are seen in infancy. The retinal, electroretinogram, and fluorescein angiographic findings are described in ten patients with Leber's congenital amaurosis who ranged in age from 13 to 36 years when first seen. All of the patients were from Honduras and were unrelated except for one pair (a brother and sister). The polymorphic appearance of the fundus is emphasized and is particularly striking in the siblings. A macular lesion (a bull's-eye maculopathy) not previously associated with Leber's congenital amaurosis is reported as a variant fundus appearance in this entity. PMID- 2234848 TI - Early magnetic resonance imaging in acute traumatic internuclear ophthalmoplegia. AB - Adduction deficiency following acute head trauma may result not only from orbital damage but also from internuclear ophthalmoplegia, and in most instances this resolves over weeks to months. To date, noninvasive imaging studies during the acute phase following injury have not been definitive in localizing the pathology. Three cases of adduction deficiency following head trauma that were caused by internuclear ophthalmoplegia are reported. A lesion in the brain stem was found in all three cases by magnetic resonance imaging in the subacute post traumatic period. These lesions were not visible on routine x-ray computed tomography obtained at the time of injury. PMID- 2234849 TI - Signs distinguishing spasmus nutans (with and without central nervous system lesions) from infantile nystagmus. AB - Clinical findings as well as eye and head movement recordings were analyzed from 23 patients with spasmus nutans without central nervous system (CNS) changes, 10 patients with spasmus nutans-like disease (head nodding, intermittent nystagmus associated with intracranial anomalies or visual pathway disorders), and 25 patients with infantile nystagmus. Ten diagnostic signs were established to differentiate between the patient groups. Although they were helpful in separating patients with infantile nystagmus from those with spasmus nutans, no difference was found between the patients with spasmus nutans with and without CNS lesions. This study indicates that eye and head movement recordings do not allow differentiation between benign spasmus nutans and spasmus nutans-like disease. The differentiation must be made on the basis of neuroimaging. PMID- 2234850 TI - Late juvenile-onset Krabbe's disease. AB - Krabbe's disease is an autosomal recessive leukodystrophy characterized by a lack of galactocerebroside beta-galactosidase activity. In contrast to the classic early infantile-onset form of Krabbe's disease, less recognized, late-onset variants exist. The authors present a case of late juvenile-onset Krabbe's disease, including the associated magnetic resonance imaging (MRI) findings. Most patients with late-onset Krabbe's disease present with visual loss due to optic atrophy. Associated gait abnormalities and parental consanguinity should increase the clinician's suspicion that a child may have late-onset Krabbe's disease. Because of the prolonged survival in late-onset Krabbe's disease, the recent development of bone marrow transplantation for these patient makes diagnosis of this disorder particularly important. PMID- 2234851 TI - Crystalline cataract and uncombable hair. Ultrastructural and biochemical findings. AB - A 7-year-old girl was found to have a progressive axial crystalline cataract located in the embryonal, fetal, and infantile nucleus. She also had the unknown association of crystalline cataract with uncombable hair. Samples of the aspirate after extracapsular cataract extraction (ECCE) showed elongated, trigonal crystals on scanning electron microscopy. On transmission electron microscopy, the crystals were surrounded by a membrane sometimes consisting of up to 30 concentric layers. The crystals were found to contain carbon, oxygen, nitrogen, sulfur, and disulfide bonds. The findings suggest that a major constituent of the crystals was a sulfur-containing aminoacid, probably cystine. Protein analysis of the remaining lens material showed elevated alpha-, beta 2-, and gamma 2- crystallin levels. Analysis of the hair root status showed hair loss in the resting phase of the hair cycle with abnormal sheathing in most hairs that were in the growth phase. PMID- 2234852 TI - Bilateral keloid-like myofibroblastic proliferations of the cornea in children. AB - Two 6-month-old white boys developed localized multifocal white nodules of the anterior corneal stroma without evidence of antecedent trauma, inflammatory disease, or familial occurrence. The first patient had bilateral lesions initially; the second patient initially had unilateral involvement followed by a corneal nodule in the second eye at 11 years of age. Light and electron microscopic studies of the lesions in both patients were similar and disclosed stromal nodules composed of proliferating myofibroblasts, activated fibroblasts, and haphazardly arranged fascicles of collagen. Immunohistochemical studies revealed that the spindle cells within the nodules expressed immunoreactivity for vimentin and alpha-smooth muscle actin. Management options for these slowly progressive corneal lesions include lamellar versus penetrating keratoplasty and topical corticosteroids. PMID- 2234853 TI - Macular dystrophy of the cornea. A systemic disorder of keratan sulfate metabolism. AB - The serum of most patients with type 1 macular corneal dystrophy (MCD), the most prevalent subtype, lacks detectable antigenic keratan sulfate (KS), and it has been postulated that such individuals may lack antigenic KS in their cartilage as well. To test this hypothesis, we studied the cornea, serum, and nasal cartilage from an MCD patient using light and electron microscopy, immunohistochemistry, and a quantitative enzyme-linked immunosorbent assay (ELISA) which uses a monoclonal antibody against a sulfated epitope on the KS chain to measure KS content. Histologically, corneal deposits seen were characteristic of MCD. No abnormal deposits were noted in the cartilage. The lack of immunoreactivity in corneal sections with antibodies against sulfated epitope on KS and the absence of this epitope in serum showed that the patient had type 1 MCD. The cartilage specimen showed no immunoreactivity in the chondrocytes or extracellular matrix. Quantitative analysis by ELISA demonstrated that the antigenic KS content of the cornea and cartilage was at least 800 times lower than that in normal controls. This provided direct evidence that the abnormality in the sulfation of keratan in type 1 MCD involves the cornea and cartilage. PMID- 2234855 TI - Glaucomatous optic nerve atrophy in small discs with low cup-to-disc ratios. AB - Glaucomatous optic nerve damage has generally been associated with high cup-to disc ratios. Fifteen eyes of nine patients with increased intraocular pressure and glaucomatous visual field loss but low cup-to-disc ratios are reported. The optic disc area was significantly (P less than 0.01) smaller than in 429 normal subjects and 556 glaucoma patients with high cup-to-disc ratios. Parapapillary chorioretinal atrophy was significantly larger and retinal nerve fiber bundles were significantly less visible than in the normal group. The latter two parameters were not significantly different in the glaucoma groups with low and high cup-to-disc ratios when the groups were matched for mean perimetric loss. The authors conclude that in eyes with small optic discs, glaucomatous optic nerve damage may be indicated more sensitively by parapapillary changes than by cup-to-disc ratios. Glaucomatous eyes with small optic nerve heads can have misleadingly low cup-to-disc ratios. PMID- 2234854 TI - Delivery of fluorescein to the anterior chamber using the corneal collagen shield. AB - Collagen corneal shields show promise as an alternative method of drug delivery to the eye. The authors quantified collagen shield delivery of sodium fluorescein to the aqueous humor in human volunteers using fluorophotometry. Collagen shields that had been immersed in 0.01% sodium fluorescein were applied to eyes of human volunteers. The shields delivered significantly more fluorescein to the aqueous humor at 2 and 4 hours compared with drops of the same concentration instilled every 30 minutes for 4 hours (P less than 0.0001 and P = 0.0003, respectively) or daily wear soft contact lenses presoaked in 0.01% fluorescein (P less than 0.0001 and P less than 0.0025, respectively). Collagen shields did not induce damage to the corneal epithelium over a 2-hour wearing period. These results suggest that the collagen shield may be superior to topical drops in delivering water-soluble compounds to the cornea and aqueous humor. PMID- 2234857 TI - Epikeratoplasty. American Academy of Ophthalmology. PMID- 2234858 TI - Contrast sensitivity and glare testing in the evaluation of anterior segment disease. American Academy of Ophthalmology. PMID- 2234856 TI - Cellular reactions on heparin surface-modified versus regular PMMA lenses during the first postoperative month. A double-masked and randomized study using specular microphotography. AB - Specular microscopy was used for investigation of cellular reactions on the intraocular lens (IOL) anterior surface of Heparin surface-modified (HSM) versus regular polymethylmethacrylate (PMMA) lenses (Pharmacia types 700C versus 700B, respectively). The double-masked randomized study included 53 patients investigated at 1 and 4 weeks postoperatively. Giant cells were only found on control lenses and more frequently at 4 weeks. Small cells were found on both lens types, but in a higher frequency on the control lenses. The number of small cells decreased during the first 4 weeks on both the control and HSM lenses. However, those control lenses that had giant cells on their surface showed an increase in the number of small cells during the same time. The results of the current study show that HSM lenses give rise to less postoperative inflammatory cellular reactions than regular PMMA lenses. PMID- 2234859 TI - The freeze-drying of Cowdria ruminantium. AB - Lyophilized tissues of mice and blood of sheep, infected with either the Kumm, the Welgevonden or the Ball 3 stock of Cowdria ruminantium, remain infective to mice and sheep after storage at 4 degree C for 90 days. Freeze-dried tissues stored at -18 degrees C and -28 degrees C are still infective after 6 months and 2 years, respectively. PMID- 2234860 TI - Concurrent babesiosis and ehrlichiosis in the dog: blood smear examination supplemented by the indirect fluorescent antibody test, using Cowdria ruminantium as antigen. AB - Giemsa-stained, peripheral blood smears of 67 dogs, showing clinical signs typical of babesiosis or reminiscent of concurrent babesiosis and ehrlichiosis, were examined for the presence of Babesia canis and Ehrlichia canis. Since Cowdria ruminantium cross-reacts with Ehrlichia, the sera of these dogs were also subjected to the indirect fluorescent antibody (IFA) test in which C. ruminantium was used as antigen. Fifty-five per cent of these dogs had mixed infections of B. canis and E. canis, as judged by blood smear examination and serology. The serum of 32% of these dogs with mixed infections reacted positively in the IFA test. Six out of 9 dogs, the blood smears of which were negative for both B. canis and E. canis, were serologically positive for E. canis. Furthermore, sero-conversion from a negative in the initial serum sample to titres of up to 1:160 in a subsequent sample was recorded in 9 out of 13 dogs with suspected mixed infection on blood smear. PMID- 2234861 TI - A comparison of haemodynamic and vasoconstrictory responses in sheep with a toxic fraction from Pachystigma pygmaeum and with the plant material. AB - ST-segment changes in the ECG, which are an indication of acute myocardial ischaemia, are obtained when a small quantity of an extract from dried Pachystigma pygmaeum is injected intravenously in sheep. When the fraction was injected subcutaneously, animals reached a crisis after about 5 h, with low values of stroke volumes and high values for pulmonary arterial pressures, pulmonary vascular resistances and heart rates. The haemodynamic changes are an indication of the development of pump failure of the heart. In sheep, injected subcutaneously with the toxic fraction, as well as for sheep dosed with plant material through rumen fistula, increased serum levels for thromboxane and increased or decreased levels for prostacycline were observed. The experimental results are interpreted as being an indication that these prostaglandines may be involved in the development of gousiekte by impeding cardiopulmonary function as a result of coronary and pulmonary vasoconstriction. The sudden death observed in some gousiekte sheep may be due to myocardial ischaemia and associated arrhythmias. PMID- 2234862 TI - The detection and isolation of a paralysis toxin present in Argas (Persicargas) walkerae. AB - One-day-old leghorn chickens were used in a laboratory assay to determine the toxicity of crude extracts of the tick Argas (Persicargas) walkerae and of fractions obtained during the isolation procedure. Extracts of unfed and engorged larvae, nymphae and females were tested using this in vivo test system. Only extracts of replete A. (P.) walkerae larvae produced paralysis. A toxic fraction was isolated from replete larval extracts by gel-permeation and ion-exchange chromatography. This fraction with a pI of 4,5, showed 2 major bands corresponding to a Mr of 32 kDa and 60 kDa after SDS-polyacrylamide gel electrophoresis. PMID- 2234863 TI - Parasites of South African wildlife. V. A. description of the males of Oesophagostomum mocambiquei Ortlepp, 1964 from warthogs, Phacochoerus aethiopicus (Pallas, 1766). AB - Oesophagostomum mocambiquei Ortlepp, 1964 was described from 9 females recovered from a warthog, Phacochoerus aethiopicus (Pallas, 1766), from northern Mozambique. Large numbers of O. mocambiquei were recovered during subsequent surveys of the parasites of warthogs from the Kruger National Park and the Hoedspruit Nature Reserve. The males, which have not yet been described, resemble those of Oesophagostomum santosdiasi Ortlepp, 1964 in the principal measurements. They can, however, be differentiated by the shape of the mouth capsule, which is round in O. mocambiquei and oval in O. santosdiasi. A simplified key for the identification of the Oesophagostomum species that occur in warthogs in South Africa and Namibia is provided and the differences between them tabulated. The names Oesophagostomum mocambiquei and Oesophagostomum santos-diasi are corrected to O. mocambiquei and O. santosdiasi respectively, since diacritic marks are not allowed under the Code of International Zoological Nomenclature. PMID- 2234864 TI - Salmonella isolated from feeds and feed ingredients during the period 1982-1988: animal and public health implications. AB - The prevalence of Salmonella in southern Africa in farm feeds and by-products of animal origin during 1982-1988 was determined. Salmonella occurred in 5.18% of the farm feed samples and in 9.54% of the by-product samples. Different serovars were isolated, some only once. The findings underestimate the true prevalence of Salmonella in farm feeds and by-products, and is representative of only the most severely contaminated products. The epidemiology of salmonellosis is discussed with special reference to the importance of multiple resistance to antibiotics, the increase in the number of cases of salmonellosis worldwide and "Salmonella free" feeds and foods. More detailed research on the role of farm feeds in the epidemiology of salmonellosis is required. Efforts should be made to increase awareness of the problem, to improve quality management at farm feed production plants and to develop efficient systems to monitor the hygienic safety of feeds and foods. PMID- 2234865 TI - Heat stress in dairy cattle under southern African conditions. II. Identification of areas of potential heat stress during summer by means of observed true and predicted temperature-humidity index values. AB - November-March are the hottest months of the year with the highest monthly mean "temperature-humidity index" (THI) in South Africa and Namibia. These 5 months are associated with severe heat stress in dairy cattle, are of critical importance for their performance and may have great economic implications for the owner as well as for the dairy industry. Firstly, compared with the existing Livestock Weather Safety index (LWSI), more relevant meteorological data can be generated when mapping South Africa and Namibia according to the LWSI modified for lactating dairy cattle (LDC). Secondly, compared with the observed true THI values alone, more relevant data on heat stress and its deleterious effects on dairy cattle performance, become available when mapping South Africa and Namibia according to the combined observed true and predicted THI values. Minimum precautions against heat stress in dairy cattle are recommended depending on THI values as classified by the LWSI for LDC. PMID- 2234866 TI - A survey of annoyance of livestock by Simulium chutteri Lewis along the Orange River, South Africa (Diptera: Simuliidae). AB - A survey by means of questionnaires was conducted along the Orange River to determine the extent of blackfly annoyance to livestock during 1984-1988. Severe annoyance reached peaks during September-November and increased over the years. Annoyance levels decreased with distance from the river with occasional severe annoyance as far away as 76 km. Annoyance levels increased with distance downstream from the P. K. le Roux dam to Augrabies (750 km). Greater water releases for increased irrigation and electricity generation may be an important reason for the higher annoyance levels. Present day high and increasing irrigation water requirements and the great length of the river probably render control by water level fluctuations impractical. Loss of condition of especially small livestock is the main consequence of annoyance by female blackflies. Decreased percentage lambing and occasional deaths were also reported. PMID- 2234867 TI - The use of filter paper discs impregnated with thionin acetate, basic fuchsin and thionin blue in the identification of Brucella species. AB - Filter paper discs impregnated with solutions containing 0.25, 0.5 and 1 mg/milliliter of thionin acetate, 0.75 and 1.5 mg/milliliter of basic fuchsin and 0.5 mg/milliliter of thionin blue were used in the typing of Brucella species. All the strains used reacted as expected, proving this new technique to be reliable in the identification of Brucella species. The method is less expensive and the results easier to interpret than those obtained with methods previously used. PMID- 2234868 TI - Epizootology of wildebeest-derived malignant catarrhal fever: possible transmission among cows and their calves in the north-western Transvaal. AB - The investigation involved 52 cases of wildebeest-derived malignant catarrhal fever in 1986 and 1989 in a herd of cattle kept in camps adjacent to a game farm harbouring a herd of approximately 330 blue wildebeest (Connochaetes taurinus). In the outbreaks, 34 cows and 18 calves died as result of the disease. The exceptionally high incidence of the disease in both cows and their calves, the low incidence in calves of unaffected cows, the relatively short period between the death of cows and their calves as well as the occurrence of the disease in 2 calves born after their mothers had been moved away from wildebeest, are indicative of transmission among cows and calves. The death of at least 6 calves within 6 weeks of birth is ascribed to intra-uterine infection while some calves that survived longer may have acquired the infection from other cattle or from wildebeest. PMID- 2234869 TI - An attempt to improve the immunization of sheep against heart-water by using different combinations of 3 stocks of Cowdria ruminantium. AB - Neither sheep immune to the Ball 3, the Kwanyanga or the Mara stocks of Cowdria ruminantium nor those immunized with combinations of these 3 stocks were protected against challenge with the Mali stock. Against challenge with the Welgevonden stock, however, immunization with each of the 3 combinations and with single stocks effected a protective immunity. PMID- 2234870 TI - An efficient medium for the isolation of Trichomonas foetus. AB - Trials were conducted to compare a modification of a commercial medium with the 2 media currently used at the Veterinary Research Institute, Onderstepoort, for the isolation of Trichomonas foetus. An antifungal agent was also added to the medium. Results obtained proved the modified medium to be more reliable for the isolation of T. foetus than the other 2, and the addition of antifungal more efficient in the control of contaminants. PMID- 2234871 TI - Introducing the 'walk-up' flap. AB - Reconstructive oral and maxillofacial surgeons often find the need for additional soft tissue even when a myocutaneous flap has been previously placed. This article introduces the principles, technique, and results of 32 "walk-up" muscle flaps derived from existing myocutaneous flaps. The anastomotic vascular ingrowth at the original myocutaneous flap's distal end permits its proximal detachment and axial vessel ligation to rotate the proximal two thirds to a tissue-deficient site. In our experience at the University of Miami, these flaps have been predictable (97% viable transfer rate), have provided vascular soft tissue in deficient areas, and have been skin grafted at their surface to increase oral lining or skin cover, among several other uses. PMID- 2234872 TI - Cephalometric analysis of long-term airway space changes with maxillary osteotomies. AB - The cephalometric radiographs of 13 patients without sleep apnea who had undergone isolated maxillary surgery were studied. The authors found increases in both the nasopharyngeal and hypopharyngeal airway spaces 3 to 5 years after surgery. The results suggest that adaptive processes occur in both the upper and lower jaw, which contribute to an enlarged airway after surgery. PMID- 2234873 TI - Psoriatic arthropathy of the temporomandibular joint. AB - A case of psoriatic arthritis of both temporomandibular joints is described with a brief review of the literature and discussion on the management of this condition. To date, psoriatic arthritis has been successfully treated by conservative means. In the case reported, surgical replacement of the condyles became necessary to eliminate pain and restore function. PMID- 2234874 TI - A study of the comparative efficacy of four common analgesics in the control of postsurgical dental pain. AB - Four common oral analgesics were tested in a single-blind trial to determine their relative efficacy in the management of postsurgical pain in 103 patients who had their impacted third molars surgically removed under general anesthesia. The analgesics tested were acetylsalicylic acid (26 patients), ibuprofen (26 patients), a paracetamol/codeine/caffeine combination (Solpadeine) (25 patients), and dihydrocodeine (26 patients). The paracetamol/codeine/caffeine combination, ibuprofen, and acetylsalicylic acid preparations produced equally effective analgesia. Dihydrocodeine was found to be a poor analgesic in this pain model. There were no adverse reactions to any of the preparations. PMID- 2234875 TI - Histologic evaluation of the width of soft tissue necrosis adjacent to carbon dioxide laser incisions. AB - This study evaluated the width of tissue necrosis lateral to carbon dioxide laser incisions on human intraoral excisional biopsy specimens. Measurements were made on specimens including epithelium, muscle, dense and loose connective tissue, and salivary gland. Results showed a mean width of tissue necrosis of 86 microns in epithelium, 85 microns in muscle, 51 microns in loose connective tissue, 96 microns in dense connective tissue, and 41 microns in salivary gland. The range of thermal necrosis in different tissue types is probably based on the water content within each type. A cellular partially homogenized zone of reversible thermal damage up to 500 microns in width was visible adjacent to the zone of thermal necrosis. The relatively narrow width of tissue necrosis with this technique may account for the claimed superior properties of laser-induced wounds compared with those created by electrosurgery. PMID- 2234876 TI - Unilateral mydriasis caused by transdermal scopolamine. AB - Contamination of the eye after handling of a transdermal scopolamine patch may cause accidental mydriasis. A simple office test is discussed to identify this pharmacologic blockade and thereby avoid an extensive neurologic workup. PMID- 2234877 TI - Autogenous transplantation of impacted maxillary canines. PMID- 2234878 TI - Propolis allergy: a cause of oral mucositis with ulceration. AB - Propolis has been used since ancient times in folk medicine for its alleged beneficial effects. It is a potent sensitizer and is well recognized as a cause of occupational allergic eczematous contact dermatitis in apiarists. Recently, there has been an increase in allergic eczematous contact dermatitis because of nonoccupational exposure to propolis in "natural products" and biocosmetics. This report describes a patient who had acute oral mucositis with ulceration as a result of using propolis-containing lozenges. PMID- 2234879 TI - Multiple myeloma and bullous lichenoid lesions: an unusual association. AB - Many associations of lichenoid reactions have been described but this case appears to be a previously unreported association--with multiple myeloma. This case also demonstrates the necessity of a mucosal biopsy with adequate hematologic and serologic investigations to obtain a definitive diagnosis. PMID- 2234880 TI - Nitrendipine-induced gingival hyperplasia. First case report. AB - Drug-induced gingival hyperplasia is well documented within the literature. It has been associated with phenytoin, cyclosporine, and calcium channel blocking agents. Nitrendipine is an experimental calcium channel blocking agent that also appears to cause the side effect of drug-induced gingival hyperplasia. The clinical and histologic presentation of this side effect and possible biochemical mechanisms of pathogenesis are discussed. PMID- 2234881 TI - Thermally induced 'nicotine' stomatitis. A case report. AB - A palatal lesion resembling "nicotine" stomatitis was found in a woman who did not smoke. However, the patient frequently drank extremely hot beverages. After she was instructed to reduce the temperature of the beverages, the lesion almost completely resolved. This suggests that heat was the primary cause of this lesion and also implicates heat as the major cause of nicotine stomatitis. PMID- 2234882 TI - The cellular composition of basal cell adenoma of the parotid gland: an immunohistochemical analysis. AB - Four cases of basal cell adenoma of the parotid gland were examined immunohistochemically to characterize their cellular composition. In all cases epithelial membrane antigen and keratin were detected in the inner luminal cells; some cells also showed positive staining for secretory functional markers, indicating their differentiation toward secretory epithelium. In tubular and trabecular types the outer cells consistently displayed an intense staining for vimentin and some were also positive for actin, indicating their myoepithelial nature. In the solid type, most tumor cells resembled the ductal cells or basal cells of larger ducts in normal gland with regard to their immunoreactivity. Our results may suggest that the proportion and arrangement of heterogeneous tumor cells are responsible for different histologic patterns of the salivary basal cell adenoma. PMID- 2234883 TI - Primary malignant melanoma in the parotid gland. AB - Reports of primary malignant melanoma arising from the parotid salivary gland are extremely rare and, to date, have been sporadic. We report a pertinent case, and tabulate and correlate the clinical findings of the 13 cases reported thus far in the literature. The most common symptom is a progressively enlarging, asymptomatic, firm, and fixed mass. Total excision has been the established treatment of choice. The contribution of radiotherapy, chemotherapy, and immunotherapy remains unclear, and it is not possible at present to predict the outcome of treatment in individual patients. Although rare, primary malignant melanoma should be considered in the differential diagnosis of parotid tumors. The clinical significance of establishing the diagnosis of primary malignant melanoma of the parotid gland is emphasized. PMID- 2234884 TI - Oral histoplasmosis as a presenting disease in acquired immunodeficiency syndrome. AB - A 43-year-old homosexual man visited his dentist with painful, nodular, ulcerated lesions on the soft palate, right buccal mucosa, and right posterior maxillary gingiva. Serologic studies for exposure to human immunodeficiency virus, performed before biopsy, were positive. Biopsy of the maxillary gingiva demonstrated sheets of histiocytes containing small intracellular yeasts, which on culture were identified as Histoplasma capsulatum. Bilateral leukoplakic lesions with some vertical furrowing involving the lateral borders of the tongue were also noted. Histologically, hyperkeratosis and fungal hyphae were identified. The patient was treated for histoplasmosis with amphotericin B, which resulted in significant improvement of the oral lesions. He was subsequently hospitalized for fatigue and dyspnea and was found to have Pneumocystis carinii pneumonia. Pulmonary status deteriorated within a 3-week period, and the patient died. Autopsy findings were negative for histoplasmosis but positive for necrotizing and cavitary P. carinii pneumonia, pulmonary and hepatic herpes simplex infections, and pulmonary and intestinal cytomegalovirus infection. PMID- 2234885 TI - An SEM investigation of the mesiolingual canal in human maxillary first and second molars. AB - The mesiolingual orifices of 21 maxillary first molars and 37 maxillary second molars were examined with the scanning electron microscope. The mesiobuccal roots of these teeth were also typed by means of a clearing technique. The results demonstrated that 90% of first molars and 70% of second molars had two canals in the mesiobuccal root. Type 3 canal systems occurred in 33% of first molars and 35% of second molars. Eighty-one percent of first molars and 59% of second molars had a separate mesiolingual canal orifice. The mean diameter of the mesiolingual orifice was 0.49 mm in first molars and 0.42 mm in second molars. The mean distance of the mesiolingual orifice from the mesiobuccal orifice was 2.31 mm in first molars and 2.06 mm in second molars. In type 3 roots, the average distance of the mesiolingual foramen to the anatomic apex was 2.0 mm for first molars and 1.45 mm for second molars. PMID- 2234886 TI - Replantation: an analysis of 29 teeth. AB - The results of replantation of 29 teeth are described. Maxillary incisors constituted 85% of 27 permanent teeth. The period between avulsion and replantation ranged from within an hour to 86 days, but the actual extraoral period was within 5 hours in all but one case. Nineteen of the 27 permanent teeth were functioning for 7 months to 6 years and 7 months postoperatively. Root resorption was the cause of tooth loss in five cases. The incidence of root resorption seemed to increase with the increase of the extraoral period, but it was not affected by the period between avulsion and replantation, the condition of supporting tissues, the degree of root formation, and the type and period of splinting, indicating multiple factors involved in determining the prognosis of replanted teeth. In conclusion, every effort should be made to preserve avulsed teeth even in unfavorable conditions. PMID- 2234887 TI - Apical closure of mature molar roots with the use of calcium hydroxide. AB - Calcium hydroxide may induce apical root closure in affected mature teeth as well as in immature teeth. Once an apical hard tissue barrier is formed, a permanent root canal filling can be safely condensed. Two cases are described in which calcium hydroxide induced apical root closure in mature molar teeth where the apical constriction was lost because of chronic inflammatory process. PMID- 2234888 TI - Quantitative evaluation of digital dental radiograph imaging systems. AB - Two digital imaging systems, a video camera and analog-to-digital converter, and a charge-coupled device linear photodiode array slide scanner, were tested for their suitability in quantitative studies of periodontal disease. The information content in the original films was estimated, and digital systems were assessed according to these requirements. Radiometric and geometric performance criteria for the digital systems were estimated from measurements and observations. The scanner-based image acquisition (digitization) system had no detectable noise and had a modulation transfer function curve superior to that of the video-based system. The scanner-based system was equivalent to the video-based system in recording radiographic film densities and had more geometric distortion than the video-based system. The comparison demonstrated the superiority of the charge coupled device linear array system for the quantification of periodontal disease extent and activity. PMID- 2234890 TI - Unusually placed molars. PMID- 2234889 TI - Cross-sectional radiography for implant site assessment. AB - An accurate tomographic technique is described for acquisition of optimal cross sectional images of implant sites before implant surgery. The described technique is applicable to tomographic systems equipped with a cephalometric head positioner. This cross-sectional tomographic technique was performed on a series of patients and the images of the first 20 patients subsequently evaluated. The cross-sectional images allowed for the characterization of the alveolar crest and visualization of anatomic structures in a buccolingual dimension while providing an accurate estimation of available vertical space from the crest. PMID- 2234891 TI - Butterfly artifact in the oral cavity. PMID- 2234893 TI - Unusual calcareous bridge. PMID- 2234894 TI - Absence of all permanent second molars. PMID- 2234892 TI - Disturbance in lip sensation. PMID- 2234895 TI - Antrolith. PMID- 2234896 TI - Rupture of a mucous retention cyst. PMID- 2234897 TI - Reissner's membrane in aging, Meniere's disease, and profound sensorineural deafness. AB - The characteristics of Reissner's membrane from 47 human cochleae with mild endolymphatic hydrops, profound sensorineural deafness and normal ears were studied by light microscopy. The highest cell densities were observed in the zones adjacent to the limbus spiralis and the stria vascularis. The cell density of Reissner's in normal ears decreased with age concomitant with an increased formation of epithelial cell clusters. In hydrops, the density increased with the exception of the apical turn. However, sporadic loss of the cells in isolated areas of the membrane was observed. The ears with profound deafness showed no significant changes compared with age-related controls. No definite relationship between Reissner's cell density and hair cell loss or strial atrophy was observed. PMID- 2234898 TI - Relationship between results of electrocochleography and caloric test in Meniere's disease. AB - The relationship between an increase in the negative summating potential (-SP) and the results of caloric tests was examined in 35 patients with unilateral Meniere's disease. The -SP was recorded by extratympanic electrocochleography. The quantitative bithermal caloric test was performed by irrigating with cool (30 degrees C) and hot (44 degrees C) water. An increased -SP was recorded in 20 of 35 patients (57%). Abnormal unilateral weakness (UW) on the involved side and abnormal directional preponderance (DP) to the involved side were observed in 16 of 35 (46%) and in 4 of 35 patients (11%), respectively. No significant correlation was found between an increased -SP and an abnormal UW and DP in Meniere's disease. PMID- 2234899 TI - Effect of mechanical trauma on the stapedial footplate after stapedectomy. A scanning electron microscopic study. AB - The possible occurrence of inner-ear trauma linked to stapedectomy was studied by scanning electron microscopy of the medial (or labyrinthine) side of human stapedial footplates after performing a hole with different instruments. The anatomic variations induced experimentally by the different procedures are presented in detail and discussed. Manual instruments were shown to induce irregularities on the rim of the hole, whilst the utilization of either electric or pneumatic drills produced more regular margins. Finally, laser-produced holes were also examined. Rather neat rims were observed, but the thermal effect produced by this device has to be considered the major parameter involved in a possible inner-ear postoperative trauma. PMID- 2234900 TI - Tympanic neurectomy: its effects on the seromucinous glands of the middle ear of cats. AB - The effect of tympanic neurectomy on the seromucinous glands of the middle ear was evaluated experimentally in cats. The operation suppressed the secretory activity of the glands and induced their atrophy, and glandular suppression was still evident 1 year postoperatively. This work points to the possibility of employing tympanic neurectomy in the treatment of refractory cases of otitis media with effusion. The operation is easy to perform, and, theoretically, it should allow drainage of the effusion and inspection of the ossicles. However, neurectomy should be carried out as completely as possible in order to achieve optimum and long-lasting effects. PMID- 2234901 TI - Cisplatin reduces epidermal growth factor receptors in squamous-cell carcinoma in vitro. Preliminary results. AB - A radioreceptor assay was used to determine the number and affinity of epidermal growth factor (EGF) receptors in a human squamous carcinoma cell line of the larynx (HLac 79) after exposure to cisplatin (DDP). Cells exposed to high concentrations of cisplatin showed about 30% fewer receptors compared to untreated and low-dose-treated cells. This reduction in the number of receptors might be responsible for the decreased growth when stimulated by EGF. Cisplatin appears to lower the concentration of EGF receptors on carcinoma cells, which might result in additional antiproliferative activity especially in carcinomas with high EGF receptor expression. PMID- 2234902 TI - Laryngoplasty with vascularized and non-vascularized auricular mucochondral grafts. An experimental study in rabbits. AB - A composite graft from the rabbit ear, consisting of cartilage, perichondrium and oral mucosa, was transposed to reconstruct a defect in the thyroid cartilage of the larynx in 10 rabbits. Five grafts were transposed as an island on an intact neurovascular pedicle; the other 5 were performed as a free graft without vascularization. After 9 weeks all the rabbits with a vascularized cartilaginous graft survived, with no sign of respiratory distress. The internal lining of the newly formed larynx was composed of undifferentiated stratified squamous cell epithelium. The survival of an intact cartilage and mucosa prevented a serious scar reaction in the neo-larynx and maintained the patency of the restored lumen. In the rabbits with non-vascularized cartilaginous grafts, there was necrosis present within the mucosal grafts, with intensive formation of granulation tissue in the transplanted region and retraction of the lumen. The present study highlights the importance of using well-vascularized composite cartilaginous grafts in laryngeal reconstruction. The possibility of utilizing a vascularized cartilaginous graft in man is discussed. PMID- 2234903 TI - Nasal mucociliary clearance in patients with nasal polyposis. AB - We have studied 30 patients (13 males and 17 females) with nasal polyposis, measuring the nasal mucociliary clearance using the saccharin test. The results have been compared with those obtained in a control group of 20 healthy subjects. The values obtained in the group with nasal polyposis (mean +/- SD = 31.7 +/- 13.4 min) were significantly higher than those of the healthy subjects (mean +/- SD = 12 +/- 6 min; p less than 0.002). These results suggest that there is a significant decrease in the nasal mucociliary clearance of patients with nasal polyposis. PMID- 2234904 TI - Laryngeal carcinoma showing multidirectional epithelial neuroendocrine and sarcomatous differentiation. PMID- 2234905 TI - Wegener's granulomatosis with otological disorders as primary symptoms. AB - Otological symptoms as initial manifestations of Wegener's granulomatosis have been observed in 3 patients. In one of them, symptoms consisted of a bilateral sensorineural hearing loss, improved by corticoid therapy. No other organ system was involved and laboratory tests remained within normal limits for 2 years after the onset of otological signs. In the other 2 patients, Wegener's granulomatosis manifested mainly as serous otitis media. Otologic involvement underscores the role of the otolaryngologist in the early diagnosis and treatment of this disease. PMID- 2234906 TI - Fluctuating hearing loss in lipoma of the cerebellopontine angle. AB - Two cases of lipoma of the cerebellopontine angle are presented. Both of them showed fluctuating hearing loss, and one case exhibited Meniere-like symptoms. In one of the cases, continued clinical surveillance is considered in view of a high chance of postoperative morbidity. PMID- 2234907 TI - [Effect of extra- and intra-cranial vascular anastomosis on regional blood flow, studied by SPECT using 99m-Tc HMPAO]. AB - Thirty-two patients suffering from occlusive cerebrovascular disease were investigated by means of 99mTc-HMPAO brain SPECT before and one month after EC-IC bypass operation. The regional cerebral blood flow was unchanged postoperatively in 19 patients, increased in 7 cases, and deteriorated in 6 patients. One patient died in the postoperative period and in another no follow-up SPECT could be performed. It is concluded that the regional cerebral blood flow, even in the absence of a morphological deficit on CT, was not improved by the operation in the majority of cases. PMID- 2234908 TI - [Correlations between cardiorespiratory reflex impairment and distal neuropathy in diabetics free of clinical symptoms of autonomic neuropathy]. AB - Signs of autonomic cardiac neuropathy and its association with distal symmetrical polyneuropathy were investigated in adult diabetic patients free from clinical symptoms of autonomic neuropathy. Cardiorespiratory reflexes were assessed by non invasive tests (deep-breathing, Valsalva manoeuvre and lying-to-standing) evaluating parasympathetic function of cardiac innervation. Measurement of motor nerve conduction velocity in both peroneal nerves and neurological physical examination were carried out for assessment of distal somatic neuropathy. Among 64 diabetics, definitive signs of cardiac autonomic neuropathy were found in 28 patients (44%), early signs of cardiac autonomic neuropathy were observed in 19 patients (30%) while no alterations were documented in 17 patients (26%). The values of motor nerve conduction velocity in peroneal nerves (41.8 +/- 0.7 m/s) were significantly (p less than 0.01) lower in patients with definitive cardiac autonomic neuropathy (n = 28) than those (45.8 +/- 1.1 m/s) of patients without any signs of cardiac autonomic neuropathy (n = 17). These latter values were, however, significantly (p less than 0.001) lower than those (53.7 +/- 0.7 m/s) of control subjects (n = 50). Abnormal results of non-invasive tests for autonomic neuropathy, i.e. alterations of cardiorespiratory reflexes indicating parasympathetic impairment in cardiac innervation could be often found in diabetics without clinical signs of autonomic neuropathy. These alterations could be frequently observed in diabetics with distal symmetrical neuropathy as well as in diabetic patients with one or more late specific complications. PMID- 2234909 TI - [Normalization of ECG after right ventricular infarct]. AB - 6-month ECG follow-up was carried out in 65 patients with right ventricular infarction accompanied by anterior (n = 17) and inferior (n = 48) left ventricular necrosis. QRS morphology and ST segment alterations were evaluated in the period of rehabilitation and 6 months later. By the end of the 6th month QRS in V3-4R returned to normal in 12 patients (18%) and there was no ST elevation in none case by this time. Normalization of QRS in V3-4R was about the same in the two groups and it was independent from the age of patients. PMID- 2234912 TI - [In memory of Janos Ambro--on the centenary of his death]. PMID- 2234910 TI - [Imported food poisoning caused by fish toxins (ciguatoxin)]. AB - Various types of fish-poisoning mainly occur in tropical areas. Saxitoxin, tetrodotoxin, scombrotoxin and clupeotoxin are heat labile while ciguatoxin, in contrast, is heat stable thus it may be the source of severe poisoning even in case of thorough cooking and baking. In December 1987 a mass alimentary poisoning occurred following ingestion of fish meat in a group returning from Cuba. The most severe case was admitted to our department with symptoms of extended paresis. Diagnosis of ciguatoxin poisoning was established based upon the history, clinical features and laboratory results. Nowadays exotic, remote "Fish poisoning" cases have to be taken into consideration even in our country. PMID- 2234911 TI - [Primary choriocarcinoma of the lung simulating tuberculosis]. AB - The authors report the case of a young female patient in whose lung they found a hollow, infiltrating lesion characteristic of tuberculosis which was removed by operation. Histologically, the lesion proved to be choriocarcinoma. Elsewhere tumour could not be detected. PMID- 2234913 TI - [Physician-agronomist or agronomist-physician: Janos Karoly L ubeck (1776-1814)]. PMID- 2234914 TI - [Perinatal serum lead levels]. PMID- 2234915 TI - [Joint involvement in septic salmonellosis]. PMID- 2234916 TI - [The practice of genetic counseling]. AB - The most important practical application of medical genetics is the genetic counselling. It is based on the specific burden of potential offspring which involves severity and treatibility of expected disorder, possibility of prenatal diagnosis, risk, etc. The separation of specific and random burdens is also very important. In Hungary a new counselling method entitled "information guidance counselling" was introduced which means an intermediate position between directive and nondirective counselling because of the expectation of family planners. PMID- 2234917 TI - [Causes and management of local tumor recurrence after low resection of the rectum]. AB - The postoperative course of 64 patients resected with EEA stapler because of their midrectal cancer have been followed. 13 (20.3%) local tumor recurrence have been observed in the first 24 postoperative months. 5 patients could be rectum exstirpated at the reexploration, only colostomy was performed in 8 cases. All the inoperabel patients have died in a year, but 3 of the exstirpated ones overlived this time. A direct connection have been observed between the Dukes stadium and the differentiation of the tumor, the distance of the distal resection line from the lower end of the tumor and the probability of the local recurrence. No connection has been found between the distance of the tumor from the linea dentata and the local tumor recurrence. On the basis of the oncological observations the deep rectal resection can be performed only by tumors in stadium Dukes A and B, if the tumor is well differentiated, there are no signs for local propagation or lymph node metastases, and more then 2 cm distal distance can be kept by the resection from the lower and of the tumor. In all other cases the rectum exstirpation must be the method of choice. PMID- 2234919 TI - [Melanoma screening in Debrecen]. AB - Melanoma screening examination has been organized in Debrecen. The aid of it is the early detection and treatment of melanoma. Different methods (educational pamphlet, postgradual training of GP's, TV, radio) help the work of dermatologists. PMID- 2234918 TI - [Subglottic laryngitis treated with corticosteroid inhalation]. AB - On basis of examinations the authors established that in case of a mild pseudocroup syndrome the inhalation of beclomethasone in itself, in more severe cases combined with racem epinephrine has a favourable effect; it shortens the period of symptoms, and effectively reduces the progress of laryngitis with resting dyspnoe. In 15 cases out of 18 patients treated without local steroids, airway stenosis increased, while in patients getting inhalative steroids only 15 cases out of 29 worsend. In practice the use of beclomethasone makes possible the home treatment in mild cases of pseudocroup. It must be considered, however, that one hour is needed while its effect develops. The progress of laryngitis can be stopped by inhalative corticosteroids, but in most severe cases they must be combined with racem epinephrine. PMID- 2234920 TI - [Gentamycin concentration in the milk of a mother after treatment by implantation of a Septopal chain]. AB - The author implanted 90 beads of Septopal into the osteomyelitic femur of a wet mother. The excretion of gentamycin in the mother's milk was continuously examined. The investigations revealed that the excretion of gentamycin with the mother's milk was so minimal that it did not signify any risk for the newborn baby. PMID- 2234921 TI - [Solitary ulcus recti simplex]. PMID- 2234922 TI - [Abuses in alternative medicine]. PMID- 2234923 TI - [Angiologic aspects of surgery of the extremities in diabetics]. PMID- 2234924 TI - [Teratogenic effects of the workplace on pregnant women]. PMID- 2234925 TI - [Surgical treatment of stomach cancer with extended removal of lymph nodes]. AB - The authors evaluate the results of extensive lymph node dissection for gastric cancer at 50 patients. It has been found that the lymph node dissection did not increase the risk of operation. The mortality rate was 2%. The average number of removed and histologically examined lymph nodes was 26. The extensive lymph node dissection and the accurate histology provided opportunity for precise staging. Their first evaluation of survival showed an encouraging improvement of prognosis regard to that of patients survival treated by traditional surgical method. Besides it they reviewed the classification of Japanese Research Society for Gastric Cancer for the lymph drainage of the stomach and the surgical technique of the lymph node dissection. PMID- 2234927 TI - [Management of intussusception in infancy by hydrostatic desinvagination under ultrasonic monitoring]. AB - The ultrasonographic diagnosis of intussusception may be a recent complementation of X-ray fluoroscopy controlled hydrostatic desinvagination. Ultrasound is also useful in follow-up of the effectiveness of conservative management. By presenting their experience gathered by successful treatment of one case, the authors' aim is to contribute to the spread of this method. PMID- 2234926 TI - [Early calcipenic osteopathy in the panoramic x-ray image of the maxillary and mandibular alveolar process of young adult alcoholics]. AB - The authors have examined 220 maxillary and mandibular panoramic roentgenograms of 55-55, all 110, between 21-34 years of age alcohol addict males and females with a complete dentitions and intact parodontium. In 19 per cent of patients developed osteoporomalacia, cystic rarefications and multiple pathologic microfractures of the alveolar spongy bone tissues. The calcipenic osteopathia was verified by the routine laboratory disorders of calcium and phosphor metabolisms, besides by the diminution of roentgenmorphometrical index of right 2nd metacarpus and tibia. The osteoporomalacia of alveolar parts preceded calcipenic osteopathia of all bones in 52 per cent of patients. A quantity of 25 50 g alcohol consumed daily would be resulting the calcipenic osteopathia after 3 5 years. Its development may be due to individual praedisposition influenced by nutritional, hormonal, genetic and hepatopancreatic factors. PMID- 2234929 TI - [The status of public health in Hungary 100 years ago]. PMID- 2234928 TI - [Remembering Pal Bugat. "Every human thought yearns to be realized"]. PMID- 2234930 TI - [Bohumil Eiselt--the Czech Markusovszky]. PMID- 2234931 TI - [Contraceptive pills and congenital abnormalities]. PMID- 2234933 TI - [Preoperative diagnosis of breast tumors in our clinic]. AB - Between 1983 and 1988 197 patients underwent mammography and fine needle aspiration cytology procedure beside physical examination before operation for breast tumor in our clinic. The sensitivity of mammography and fine needle aspiration cytology were 81.9 and 66.1%, their specificities were 91.2 and 95%, the specificity of physical examination was 97.7%. When all three examinations indicated malignancy, this was confirmed by histology without exception. When the examinations showed benign lesion in concert, four of the 26 diagnoses were false, histology proved breast cancer smaller than 2 centimetres in diameter without lymph node metastases in each case. Those aspirations which were considered unsatisfactory because of the lack of cells supported the diagnosis of a benign tumor raised by physical examination and mammography. Our data indicate that the diagnosis yielded by the combination of the three examinations may support therapy more than it does in the present. PMID- 2234932 TI - [Surgical management of corrosive lesions of the esophagus]. PMID- 2234935 TI - [Plasma fibronectin level in thyroid disease]. AB - Fibronectins are widespread components of connective tissues and their production is partly under hormonal control. A study was undertaken to reveal the influence of thyroid diseases on plasma fibronectin level. It is stated that compared with a euthyroid control group (n = 33; 436 +/- 82 micrograms/ml) plasma fibronectin content is significantly higher in untreated, overt hyperthyroidism (n = 27; 1036 +/- 389 micrograms/ml), while its plasma level is lower in hypothyroidism (n = 18; 230 +/- 123 micrograms/ml). Data hint to the possibility that the measurement of plasma fibronectin level may yield a help to assess the effect of thyroid hormones at target organ (connective tissue) level. PMID- 2234934 TI - [Fetal diagnosis of Edwards syndrome]. AB - Eight cases of Edward's syndrome were found prenatally by cytogenetical analysis of 1680 pregnant women. It has been estimated that after Down's syndrome Edwards's syndrome is the most frequently encountered chromosomal abnormality. This syndrome is associated with high rate of anomalies detectable by ultrasound (e.g. omphalocele, polyhydramnion, growth retardation). Here it is discussed in relation with sonographical findings related to Edwards's syndrome and representing clear indications for chromosomal analysis. The authors call attention to the importance of the diagnosis of Edward's syndrome at each gestational age. PMID- 2234937 TI - [Indications for ultrasonography in abdominal injuries, based on a 5-year case load]. AB - The authors performed during 5 years 2620 emergency ultrasonographies of 34,873 ultrasonographic examinations. In 640 cases the examinations were carried out with injured patients. The results were positive in 46 cases. The distribution of positive cases are presented and certain cases are described. On the basis of literary data and their own experiences the authors summarize the advantages and indications of ultrasonography and deal briefly with the order of sequence of image-forming diagnostics emphasizing the primary role of ultrasonography. It is stressed that with the joint evaluation of the clinical picture and ultrasonography no other intervention was required with 16 patients than a close observation whereas acute surgery had to be performed with 17 patients. PMID- 2234936 TI - [Recombinant human erythropoietin in the therapy of anemia in hemodialyzed patients]. AB - The authors reported on a three month long EPREX (human recombinant erythropoietin) therapy of 5 hemodialysis patients for the treatment of their anemia. The drug was administered in bolus form 2 or 3 times a week after dialysis in a dose of 50 to 150 IU/bodyweight increased gradually in every (or every second) week. Hgb ad Htk values were determined once a week while erythrocyte, leukocyte, thrombocyte and reticulocyte count once a month. Serum iron, TIBC, serum ferritin, BUN, serum creatinine, urea, serum ions, liver function assays, serum lipids and amylase were also established. Hgb, Htk levels and reticulocyte count have significantly increased in the 4th week of treatment already, severe anemia ceased with improved appetite, general condition and physical strength. Serum urea and LDH levels significantly increased while SGOT decreased. No significant change in leukocyte and thrombocyte count, serum Na, K, Ca, P, Cl, BUN, creatinine, total protein level, serum albumin, bilirubin, alkaline phosphatase, GGT, GPT, amylase and blood sugar as well as serum lipid level were observed. No adverse reactions occurred during the treatment. After the three gradually decreased and within 6 weeks they had to be transfused again. In three patients the need for transfusion has significantly grown after the treatment. The authors consider EPREX a highly efficient drug in the treatment of anemia in dialysis patients. PMID- 2234938 TI - [Epidemiologic study of primary liver cancer in Vas County]. AB - The incidence of primary liver carcinoma in the last twelve years was investigated retrospectively in the county Vas. A continuously increasing tumor frequency was found, by the end of the period the value had doubled. The phenomenon attained nearly exclusively the male population while no change could be seen in females. For further clarification comparative investigations into the association between chronic HBV infection and chronic alcohol abuse as well and hepatic carcinoma were performed. Changes in these factors cannot fully explain the gross increase in hepatic tumor incidence, the effect of other risk factors has to be suspected. PMID- 2234939 TI - [Quality assurance in clinical laboratory diagnosis]. AB - Both the internal and the external quality controls are necessary to achieve reliable and comparable laboratory tests. The internal quality control includes preanalytical, analytical and postanalytical checking of factors to eliminate all interferences of laboratory tests. The use of reliable methods which result in a good accuracy and precision, however, can provide results which are not comparable to the results of other laboratories. The role of the external quality control is to check differences between the laboratories and to make the results as comparable as possible. The accuracy and precision of Hungarian laboratories improved during the past decade which can be attributed to the better technical conditions, on the one hand, and to the regular internal and external quality control, on the other hand. An increasing number of the small laboratories, mostly in the service of general practitioners, are unable to perform the same quality of laboratory tests as that of the central laboratories, since their technical conditions are old-fashioned and inadequate to use up-to-date methods. The urgency of improvement in technical condition of small laboratories is obvious from both professional and economical reasons. PMID- 2234940 TI - [Leukocyte migration inhibition test in celiac disease]. AB - The leukocyte migration inhibition test is a method used to assess the cell mediated immune function. The authors examined 251 samples for a period of 3 years; 169 samples from celiac patients and 82 were control. The sensitivity of this test was 34/35 (97%) in proved gluten sensitive patients, but this was found after repeating the test at different periods of time. According to these results the authors conclude that the efficacy of this test is less sensitive in the newly diagnosed celiac patients, which means that it is not suitable for screening purpose, but useful for detecting gliadin sensitivity during the diagnostic period of celiac disease (e. i. the 3 biopsies). LMT may be used to indicate the proper time for the 2nd and/or 3rd biopsy, and can also be used to reveal the gluten-free diet defaults. The authors agree with those who believe that this test cannot substitute the performance of the small intestinal biopsy. PMID- 2234941 TI - [The significance of hypocitruria in calcium oxalate induced nephrolithiasis]. AB - The citrate concentration of the daily collected urine was measured by citrate lyase method in 25 untreated patients with recurrent calcium stone disease (10 hypercalciuric and 15 normocalciuric) and in 11 patients with stone disease treated with hydrochlorothiazide and in 16 healthy controls. We found a great variancy of the results what rather looks like biological than methodic type. The concentration (1.99 +/- 1.33 mmol/l in normocalciuric and 2.77 +/- 1.62 in hypercalciuric stone formers but 5.06 +/- 2.81 in controls) and the daily output of the urinary citrate (2.74 +/- 1.38 mmol/d and 4.24 +/- 1.69 vs. 4.41 +/- 1.85) but not the citrate/creatinine ratio was significantly less in about the half of stone formers. The hypocitraturia was frequent in the normocalciuric and very rare in the hypercalciuric group of the renal stone patients. Measurement of the urine citrate concentration is more sensitive tool in the diagnosis of hypocitraturic state than daily citrate output while the latter is more characteristic for the patient, so common study of the two parameters is recommended. PMID- 2234942 TI - [Early results of balloon catheter dilatation in ilio-femoral-popliteal arterial occlusion]. AB - Since 1981 intraoperative balloon dilatation has been performed in 78 patients suffering from occlusive arterial disease of the lower extremities. In 34 patients the proximal iliac stenosis was dilated (common iliac artery: 15 and external iliac artery: 27) in association with a femoro-popliteal reconstruction. In 44 patients, the femoro-popliteal segment distal to an ilio-femoral reconstruction was dilated. In the early postoperative period (0-30 days) there was no reocclusion in the group of proximal dilation. In the other group, where the out-flow tract was dilated, in one case femoral amputation, while in another patient reoperation was necessary because of early reocclusion. The combining intraoperative balloon dilatation with surgical reconstruction may decrease the risk, and simplify the management of patients with multiple vascular lesions and it is valuable adjunct to vascular surgery to improve inflow or outflow. PMID- 2234943 TI - [Liver tumors caused by androgenic steroids]. AB - 11 hepatocellular tumours associated with the long term use of androgenic steroids were reported. Three of the tumours were seen on the basis of diffuse peliosis hepatis. One of the 11 tumours was benign hepatocellular adenoma. In one case malignant transformation of an adenoma was observed. Nine tumours proved to be highly differentiated hepatocellular carcinomas. Metastases were observed in three cases. Histological and electron microscopical peculiarities of the tumours were the accumulation of glycogen in the cytoplasm of tumour cells, nuclear inclusions, and great number of peculiar formed vessels. The last case is a rarity. One year after the needle biopsy implantation of hepatocellular carcinoma was observed with several tumorous metastases at the site of the previous biopsy. The authors suggest regular hepatic control by ultrasound examinations of patients on sexual steroid hormones. PMID- 2234945 TI - [What innovations does the recent change in the nursing legislation cause?]. PMID- 2234944 TI - [T gamma-lymphoproliferative disease]. AB - The case of a rare type of T-cell malignant lymphomas, clinically with a relatively favorable course, a T gamma-lymphoproliferative disease (T gamma-cell chronic lymphocytic leukaemia) was presented. The cytomorphological, cytochemical, immuncytochemical and cytogenetical markers and functional tests of the peripheral blood lymphocytes from the patient were tested. The leukaemic cells with light- and electron microscopy showed the so called LGL (large granular lymphocyte) morphology with multifocal reactions of acid hydrolase enzymes. These cells also expressed IgG-Fc-receptor, CD 8 monoclonal antibody positivity and a monoclonally rearranged T-cell receptor gen expression. Functionally the patient's lymphocytes developed a blastic response to the T-cell mitogen Concanavalin A (ConA), they suppressed the immunoglobulin production of B lymphocytes in co-cultures and had a normal NK-activity but decreased ADCC values. The patient was diagnosed by blood, bone marrow and lymph node examination and does not need any therapy. This case was published because of it's diagnostic, immunological and prognostical interests. PMID- 2234946 TI - [Education in nursing--formation of the personality]. PMID- 2234947 TI - [From custodian in a mental hospital to psychiatric nurse. A new profession is introduced]. PMID- 2234948 TI - [Nursing care of patients with stroke]. PMID- 2234949 TI - [5 years of Austrian AIDS assistance. AIDS knows no differences, no boundaries]. PMID- 2234950 TI - [New ways for better understanding between family and nursing personnel]. PMID- 2234951 TI - [Report on the inquiry on personnel procurement in Austrian health facilities]. PMID- 2234953 TI - [15 years of toxoplasmosis surveillance of pregnant women in Austria. An exemplary results in the prevention of neonatal infection]. PMID- 2234952 TI - [Chlamydia--only the name is beautiful]. PMID- 2234954 TI - [Health care of tomorrow: synergies instead of hopelessness]. PMID- 2234955 TI - [The Graz pediatric nursing school makes contact with Marburg nursing high school students]. PMID- 2234956 TI - [Pelvic tilt and leg length discrepancy]. AB - Pelvic obliquity caused by leg length discrepancy is a problem facing patients with a wide variety of conditions. It is the degree of discrepancy and the growth pattern of the legs that usually govern treatment decisions, with the cause of the discrepancy having little influence. We analyzed the results recorded in 345 patients with pelvic obliquity caused by leg length inequality operated on between 1969 and 1989. In 146 patients a shortening procedure was done and in 199 patients a lengthening procedure. Biological bone growth stimulation did not prove to be predictable and effective in 65 cases. In 134 patients and 138 segments a distraction procedure was performed. In 26 segments the technique was according to Wagner; in 37 cases the Ilizarov fixator was used and in 75 the Orthofix device. Excellent results were obtained in 65% and good results in 23%; the condition became worse in 12%. Analysis of the results justifies the use of epiphysiodesis, shortening osteotomies and bone lengthening according to the biological principles investigated by Ilizarov in the presence of well-defined indications outlined in this report. Patients with a discrepancy of up to 2-3 cm are treated conservatively by shoe lift. For patients with a leg length inequality of 3-5 cm, epiphysiodesis or shortening osteotomy is still a good indication although lengthening procedures can also be performed. Discrepancies between 5 and 15 cm are treated mainly by lengthening operations. New lengthening techniques such as corticotomy and callus distraction, as well as new external fixation systems like Orthofix and Ilizarov, have made bone lengthening a less risky, easier, and more effective procedure. In a growing child, careful clinical and radiological assessment and repeated analysis of past growth in order to predict future growth can provide an exact plan for effective treatment, which often consists of bone lengthening, combined with shortening procedures on the contralateral side to establish leg length equality even in cases when there is 20 cm difference. Surgical treatment can be especially gratifying when anatomical, cosmetic and functional symmetry is restored and a lifetime of shoe lifts, braces or prostheses can be avoided. PMID- 2234958 TI - [Pelvic tilt and leg length correction]. AB - Pelvic tilt is often the consequence of a discrepancy in leg length and can be corrected either with orthotic devices or by operative equalization of the leg length. However, pelvic tilt can also occur independently of the leg length in cases of asymmetry of the pelvis, malposition of the hip joint or contracted scoliotic deviation of the spine. In such cases with complex deformities correction of the pelvic tilt should aim a balanced body posture rather than necessarily a symmetric level of the iliac crests. PMID- 2234957 TI - [Lower leg lengthening using the Ilizarov system. Presentation of the various surgical techniques and analysis of lower leg lengthening procedures performed 1986-1989]. AB - The technique of lengthening the tibia with the Ilisarov device is explained. Different variations (bifocal or simultaneous) of the method are demonstrated, as well as the results of 53 cases of tibia lengthening in 37 patients of our hospital between 1986 and 1989. In 14 patients, a second operative procedure was necessary during treatment. In no case was internal fixation or grafting necessary. The Ilisarov ring fixator is very efficient, especially in major lengthening procedures and for simultaneous correction of deformities. PMID- 2234959 TI - [Pelvic abnormalities affecting the statics of the vertebral column]. AB - Of all the bony anomalies of the pelvis, unilateral developmental disturbances of the body of the iliac bone and the lateral parts of the os sacrum mainly affect the statics of the vertebral column. After a short description of the normal development of the os coxae and os sacrum, an attempt is made to systematize these anomalies and explain them from a developmental point of view. This is achieved by studying anatomical specimens and clinical cases. Primary disturbances concerning the growing of the cartilaginous epiphysis itself or secondary disturbances, which result from unilateral muscular palsy, can be responsible for retarded development of the body of the iliac bone. Unilateral dysplasia of the lateral part of the os sacrum could be based on disturbances of the precartilage. This is also thought to be the reason for asymmetrical formations of so-called transitional vertebrae. PMID- 2234960 TI - [Transiliac leg lengthening: experiences with a modified Salter osteotomy]. AB - Transiliac limb lengthening osteotomy is a modified Salter innominate osteotomy which uses a trapezoidal interposition bone graft instead of the usual triangular graft to achieve up to 3 cm of intrapelvic lengthening. It allows correction of certain forms of postural imbalance and pelvic obliquity, as well as allowing an optimal and variable amount of acetabular redirection. This review of 105 patients who have undergone the procedure at our institution revealed the following indications: decompensated scoliosis, 26 patients; acetabular dysplasia with ipsilateral femoral shortening, 34 patients; intrapelvic asymmetry, 7 patients; pure limb length inequality, 38 patients. Intrapelvic lengthening averaged 2.5 cm. Correction of decompensated scoliotic curves averaged 7 degrees reduction in Cobb angle. Improvement in center-edge angle in patients with hip dysplasia averaged 17 degrees. Reduction in size of shoe lift required to balance the trunk in all cases was correlated closely with the intrapelvic lengthening achieved. Complications included two transient neurapraxias (one femoral, one femoral and sciatic), two cases of sacroiliac subluxation (one patient with myelodysplasia, and one patient with polio), three cases of partial graft collapse, and six instances of broken fixation pins, and three deep wound infections. No patient had chondrolysis or avascular necrosis of the femoral head. After average follow-up of nearly 5 years (minimum follow-up 2 years), patients who underwent transiliac limb lengthening osteotomy for correction of postural imbalance for various causes retained satisfactory correction. PMID- 2234961 TI - [Pelvic tilt in neuromuscular diseases]. AB - On the basis of a study of the literature and observations in 53 of our own patients, we attempted to establish the cause and best treatment for neuropathic oblique pelvis. In addition, we tried to find out if certain kinds of neurologic dysfunctions coincide with certain kinds of oblique pelvis. It is highly probable that this pelvis malformation is the result of neuropathic spinal deformity. Severe oblique pelvis and scoliosis can be related to the severity of the neurologic dysfunction. Hip dislocation is not the reason for oblique pelvis. It can be assumed that hip dislocation, on the one hand, and oblique pelvis and scoliosis on the other can influence each other. To correct oblique pelvis, the neuropathic spinal deformity must be corrected. Anterior and posterior fusion, including the lumbosacral junction, give the best results. PMID- 2234962 TI - [CD instrumentation in pelvic tilt]. AB - Our realistic definition of pelvic obliquity is: any fixed malalignment existing between the spinal and pelvic structure in the frontal, sagittal and horizontal plane. The pelvic unit--with rare exceptions--must be considered one unique vertebra, an intercalary bone between the trunk and lower limbs. Like a structural vertebra in a scoliotic spine, the pelvic unit can be distorted in structure. The etiologies of pelvic obliquity can be divided into three major levels: below, inside and above the pelvis. Preoperative surgical planning must consider the position of the pelvis in the three dimensions. The technical options of pelvic fixation are described: alar staples, sacral screws, the cannulated iliosacral screw and finally the Galveston technique. The surgical technique is described. The results are presented in about 80 cases of CD instrumentation with pelvic fixation. For preoperative hyperlordosis a mean correction of 40 degree was achieved and for preoperative hyperkyphosis a mean correction of 66 degree. PMID- 2234963 TI - [The Luque-Galveston operation in the treatment of neuropathic pelvic tilt]. AB - A series of 17 patients with neuromuscular pelvic obliquity underwent Luque Galveston instrumentation. None of these patients had an increased neurologic deficit. One intraoperative death occurred due to pulmonary air embolism. It was possible to follow up 13 patients for an average of 2.7 years. The average correction achieved was from 97.6 degree to 38.8 degree for pronounce unbalanced lumbar or thoracolumbar curves: the correction loss averaged 3.6%. Combination with anterior correction or fusion in 38% is believed to be the factor that enabled us to reduce the incidence of pseudarthrosis and implant failure. PMID- 2234965 TI - [Cancer of the retrocricoid region]. AB - Five cases of the postcricoid carcinoma surgically treated during the last 6 years were described. During the same period 20 other patients with hypopharyngeal (piriform sinus) and 311 laryngeal cancer were operated upon. PMID- 2234964 TI - [Cryosurgery of precancerous conditions of the oral cavity and pharynx]. AB - In ENT Clinic, II Faculty of Medical Academy in Warszawa 108 patients with precancerous lesions were treated by cryosurgery during the years 1975-84. In 43 patients the lesions were in oral and in pharyngeal cavities, 33 out of 43 have had before the cryosurgery some form of therapy, conservative or radical without lasting effects. In all treated cryosurgically patients the positive results were obtained, which were consecutively verified during 3 to 9 years of observations. There were no malignant transformations, no other complications. The authors found, that the cryosurgery is a promising method of therapy in precancerous lesions. PMID- 2234966 TI - [A card for selective laryngeal examinations adapted for computerized data processing]. PMID- 2234968 TI - [Autogeneic bone transplants in the treatment of nose deformities]. AB - The late results of the nasal reconstruction by means of the autogenic osseous grafts from hip were described. 24 patients were described after being controlled 3 to 15 years after surgery. The deteriorations of the cosmetic effects were observed, because of the graft resorption. The complications at the place of taking graft were also possible. However, the authors stressed the usefulness of this autogenic osseous graft method of surgery. PMID- 2234967 TI - [Pleomorphic adenoma of atypical localization]. AB - The authors described 4 cases of multiform adenomata located in other than parotid gland sites. The diagnostic difficulties were stressed as well as the necessity of the histologic verification. PMID- 2234969 TI - [Various forms of mycoses of the oral cavity, pharynx, nasal cavity, paranasal sinuses, larynx and ear. II. Candidiasis and cryptococcosis]. PMID- 2234971 TI - [Tonsillectomy. Analysis of the data for the 25-year period]. AB - The author analysed the 38734 out of 39653 tonsillectomies performed in region of Gdansk during the years 1961-85. Age, sex and kind of intervention were evaluated (adenoidectomy, tonsillectomy, adenotonsillectomy and others). The frequency of above mentioned surgery was reduced during these 23 years by 32% (from 14.5 to 9.8 for 10,000). The great majority of this surgery was performed in children aged 3 to 7 years. The rarest age was below 3 and over 40. Under the age of 11 years prevailed boys, over 11 girls. Adenoidectomy represented 65% of cases, adenotonsillectomy only 6.6%. The tonsillotomy was also present. The author discussed the reason of decreasing number of tonsillectomy. PMID- 2234970 TI - [Cytological examination of nasal discharge before and after local administration of flunisolide (syntaris)]. AB - The influence of syntaris therapy on nasal mucosa was testified by means of the cytologic examinations. After therapy the number of the cylindric multilayer epithelial and inflammatory cells was lowered. No cell damage was observed. PMID- 2234972 TI - [Directional hearing in relation to individual circadian biorhythm]. AB - Acuity angle of the directional hearing was investigated in connection with the individual circadian rhythm. Two groups of 15 persons represented the morning and evening form of the circadian rhythm. Body temperature fixed the rhythm character. The evaluations of the angle acuity of the directional hearing were performed in the highest and the lowest point of body temperature as well as in the neutral point, which was determined in the morning group in the middle between the two extremes. The possibility of the sound localization in individual and linked with the body temperature circadian rhythm. PMID- 2234973 TI - [Problem of hereditary deafness]. PMID- 2234974 TI - [Post-influenza parageusia]. AB - A case of postinfluenzal qualitative taste disorders lasting over two years was described. After short treatment subjective symptoms subsided completely and the results of the gustometric tests normalized themselves. PMID- 2234975 TI - [Ludwik Guranowski (1853-1926)--otologist and co-founder of the Polish Otolaryngological Society]. AB - The life, work and scientific activity of Ludwik Guranowski a known Warsaw Doctor were presented. The review of his scientific publications, practice, social and publishing activity was also described, specially in connection with the edition of "Polski Slownik Lekarski" by Stanislaw Kosminski. The personality traits of this appreciated man were also depicted. PMID- 2234976 TI - [Neonatal sepsis: bases and possibilities for immunotherapy and immunoprophylaxis. 1: Maturation of immune mechanisms in the fetus and in newborn infants]. PMID- 2234978 TI - [Neonatal sepsis: bases and possibilities for immunotherapy and immunoprophylaxis. 3: Immunoprophylaxis]. AB - This paper reviews several specific and nonspecific procedures for immunoprophylaxis to prevent bacteriological infections in preterm and term newborns. An active or passive immunization is limited necessarily by the wide range of organisms causing neonatal infections. There exist first experiences regarding the prophylactic use of intravenous gammaglobulins for high-risk neonates or pregnant women with symptoms of infection and at risk for preterm delivery. Bacterial polysaccharide vaccines are under development, but up to now far off any universal availability. PMID- 2234977 TI - [Neonatal sepsis: bases and possibilities for immunotherapy and immunoprophylaxis. 2: Immunotherapy]. AB - The physiological immunodeficiency of preterm and term newborns is the major cause of their increased susceptibility to infections. Although nonspecific and specific host defence mechanisms are morphologically intact, there are functional and quantitative defects. Supportive immunotherapy is required to equalize these immunological defects. This article reviews topical possibilities for immunotherapy of neonatal sepsis (exchange transfusion, transfusion of fresh blood or fresh plasma, granulocyte transfusion, use of immunoglobulins, fibronectin, interferon and colony-stimulating factor). PMID- 2234979 TI - The effect of antibiotics on the function of the phagocytic system. AB - The present paper reviews the effect of various antibiotics (ATB) on the cells of the phagocytic system. The first part deals with an indirect mechanism of action of ATB, i.e. with changes induced in the bacterial cell which in turn renders these bacteria susceptible to phagocytosis. In the second part, the direct effect of ATB on phagocytic cells is discussed: binding of ATB to phagocytes, penetration into the cell, change in chemotactic (migratory) activity, effects on ingestion of particles, intracellular killing of bacteria and on phagocytosis associated metabolic changes (e.g. chemiluminescence). PMID- 2234981 TI - [Adrenaline and noradrenaline levels in 10-12-year-old boys during a mathematics test]. AB - Blood plasma adrenaline and noradrenaline levels were measured using radio-enzyme techniques in 53 normally intelligent boys aged 10 to 12 years with and without Attention Deficit Disorders. The measurements were performed while the subjects were at rest and during a calculation load test. An anticipatory effect in the release of catecholamine and phasic phenomena were observed. Intelligence and mental lability are implicated in catecholamine release during load situations als well as genetic factors. PMID- 2234980 TI - [Neuromuscular diseases and respiratory insufficiency in newborn infants]. AB - Myopathological examinations which served to gain information on the potential impact of neuromuscular disease on the syndrome of perinatal respiratory failure included 47 consecutively deceased premature infants and neonates. A definite muscular disease could not be safety diagnosed in any case. However, only a very small number of investigations and data on the initial (possibly prenatal) manifestations have been available up to now. We found a total of 11 cases with increased intrafibrillary fat deposits coupled with mitochondrial aggregations in three cases. In seven cases, we found a retarded maturation ranging from three to nine weeks. Focally manifest myopathic changes were recorded in three cases. In one case, a large-group atrophy was found which might indicate the existence of a defect in the region of the second motor neuron. Biochemical backup investigations are necessary to be able to assess the relatively high incidence of increased fat deposits. We consider myopathological examinations of premature infants who died of respiratory failure to be desirable because far more comprehensive studies are necessary to be able to assess the importance of perinatally occurring muscular changes for the diagnosis of neuromuscular diseases. PMID- 2234982 TI - Spontaneous growth in Turner's syndrome. AB - The natural course of growth in Turner's syndrome is demonstrated on the basis of growth data from untreated patients. The mean adult height was found to be 145.5 cm (range 136-166 cm), the growth curve was similar to that in comparable studies. A decreased growth potency of skeletal (and other) cell populations seems to be the causal defect, beginning with intrauterine growth retardation. Special other causes like metabolic or endocrine changes could be excluded. PMID- 2234983 TI - [Grey value analysis of the ultrasonic image of the thyroid in children]. AB - Simultaneously with the sonography of the infantile thyroid gland in addition to the description of the echo texture we tried to elaborate with the aid of a grey value analysis quantitatively comparable parameters for healthy thyroid glands. The thyroid gland of newborn showed by 17.4 the lowest mean grey-value. In schoolchildren it ranges between 25.5 and 31.0. Consequently the differences in grey-values objectively found out may be of use for diagnostics of thyroid diseases in infancy by the fact that before the rear of values dependent on age abnormalities will become better percentile. PMID- 2234984 TI - [75 years of Gottfried von Preyer's pediatric hospital of the city of Vienna]. PMID- 2234986 TI - [Allergy diagnosis: indication and evaluation]. AB - Allergy diagnosis is based on history, skin-test, RAST and lung functions test. For skin-test a modified PRICK-test is used. In allergic rhinitis and bronchial asthma the evaluation of this test is clear, in food-allergies however 50% false positive resp. negative results are seen. Very difficult is the diagnosis in drug allergies. In atopic dermatitis and contact-eczema a patch-test has to be done too. PMID- 2234985 TI - [Atopy: definition--pathogenesis]. AB - After a short historical review about the detection of reagins by Coca and Prausnitz-Kustner 1921-1923 and about their physico-chemical characterisation as IgE-antibodies by Ishizaka and Johansson 1967-1968 the definition and the clinical relevance of atopy is discussed. The IgE-regulation by interleukins and the pathomechanism of IgE-mediated allergies is reviewed. Of special importance is the IgE-mediated inflammatory late-reaction and the--therefore caused- unspecific hyperreactivity of the stricken tissue, both characteristic features of asthma bronchiale as well as atopic dermatitis. PMID- 2234987 TI - [Antibody deficiency in obstructive lung diseases]. AB - Severe chronic chest disease is the most serious complication in patients with antibody deficiency syndromes. IgG-subclass-deficiencies were a frequent finding in patients with obstructive lung disease and in patients with sinopulmonary infections. In the patient population referred to us for immunological investigation recurrent infection of the upper and lower respiratory tract was the most common reason to suspect undue susceptibility to infection. In 1034 pediatric patients analyzed 299 were found to be deficient in one of several IgG subclasses. In a group of 30 children, all of whom had severe lung disease and normal concentrations of serum IgG, IgA and IgM, airway-obstruction has been diagnosed in 19. 20 of the 30 patients had IgG-subclass-deficiency. The large percentage of IgG-subclass-deficiencies in this group of patients indicates that immunological disregulation is likely to contribute to the pathogenesis of chronic lung disease. PMID- 2234988 TI - [Pollinosis and bronchial asthma: pathogenesis, immunology, clinical aspects]. AB - Rhinoconjunctivitis induced by pollen exposure and bronchial asthma are generally easily recognizable clinically. In asthma a number of differential diagnoses such as ciliary dyskinesia, cystic fibrosis and gastro-oesophageal reflux must be considered. The predominant symptoms are coughing and wheezing. Investigations into the complex nature of mediator release and IgE synthesis have established a predominantly inflammatory pattern of reactions largely responsible for induction and maintenance of bronchial hyperresponsiveness due to both acute and chronic processes. Future therapeutic consequences may be derived from anti-inflammatory strategies. This has already lead to reassessment and upgrading of use of corticosteroids in paediatric asthma. PMID- 2234989 TI - [Pathogenesis and clinical aspects of atopic dermatitis]. AB - Atopic dermatitis (a. D.) is a chronically relapsing inflammatory disease of the skin caused by a genetically transmitted hypersensitivity to environmental substances. Its pathogenesis is complex and multifactorial: heredity of atopic constitution, disturbances of humoral (hyperimmunoglobulinemia-E) and cellular (defect of suppressor-T-cells) immunity, abnormal vascular reactions and abnormal skin functions. A. D. shows different forms in different age groups: Eczema infantum in infancy, Eczema flexurarum in childhood and Neurodermatitis disseminata and pruriginosa while and after puberty. Typically for all forms is a pruritus and the status neurodermiticus. The healing of a. D. is spontaneously possible at any time, but not predictable for a special case. PMID- 2234990 TI - [Therapy of bronchial asthma]. AB - Asthma stems from chronic inflammatory changes in the bronchial mucosa: its long term treatment is mainly based on the antiinflammatory action of the employed substances. Topical (aerosol) treatment is considered as the most effective route of medication; availability of new substances and new aerosols in Austria requires a revision of previously established treatment strategies. Such revised strategies are presented for schoolchildren, babies and toddlers respectively; they follow the same principles, but differ in respect to the preferred method of topical medication. In addition, coexistent allergy has to be evaluated and treated on an individualized basis; occasionally, so-called "tertiary strategies" of asthma treatment are employed as well. PMID- 2234991 TI - [Recommendations and guidelines for the treatment of atopic dermatitis]. AB - Till now no causal and healing treatment of atopic dermatitis (a. D.) is known. About this fact and about the relapsing course of a. D. the parents of the atopic children have to be informed before starting treatment. The principles of treatment are avoiding of pruritus and scratching, keeping the skin cool and humid, and avoiding of bacterial superinfections. Topic steroid-treatment is very effective, dose and application however have to be strongly controlled. The nutrition of children with a. D. should be as normal as possible, extreme regimes of diet have to be avoided. Very essential is a consequent cure of the skin, especially in the symptom-free intervals, keeping the skin cool and humid and avoiding all mechanical and chemical irritants. PMID- 2234992 TI - Antinociception and cardiovascular responses produced by electrical stimulation in the nucleus tractus solitarius, nucleus reticularis ventralis, and the caudal medulla. AB - In experiment 1, quantitative regional comparisons of the antinociceptive and cardiovascular responses produced by electrical stimulation in the caudal medulla, including regions such as the nucleus tractus solitarius (NTS), nucleus reticularis ventralis (NRV), nucleus reticularis gigantocellularis (NRGC), nucleus reticularis paragigantocellularis (NRPGC), nucleus raphe obscurus (NRO), and medial portions of the lateral reticular nucleus (LRN), were made in the rat. Electrical stimulation in all of these regions resulted in inhibition of the nociceptive tail-flick reflex, although the threshold intensity for inhibition was greater for sites in NTS compared to many sites ventral to the NTS. Antinociception was generally accompanied by an increase in mean arterial blood pressure, with the exception of sites in the NRO, where depressor responses were evoked by stimulation. Detailed comparisons between the NTS and NRV revealed that greater intensities of electrical stimulation were required to produce antinociception for sites in the NTS as compared to the NRV. There were no significant differences in threshold intensities for antinociception as a function of rostrocaudal subdivisions of the NTS, but the lateral subdivision of the NTS was significantly more efficacious than the medial subdivision. This mediolateral difference within NTS was primarily due to stimulation in medial sites producing overt movements in some animals, probably due to stimulation of adjacent midline nuclei or pathways. Within the NRV, thresholds for inhibition of the tail-flick reflex were greater for sites in the dorsal subdivision as compared to the ventral subdivision, which contains spinopetal projections from the NRM. The slopes of the lines of recruitment for inhibition of the tail-flick reflex at stimulation sites in either the NTS or NRV were both very steep, similar to other forms of antinociception. In experiment 2, the pulse duration of electrical stimulation was varied for sites of stimulation in the lateral NTS and NRV to generate strength-duration curves. This experiment confirmed that stimulation sites in the lateral NTS required greater current intensities to inhibit the tail-flick reflex than sites in the NRV. However, the chronaxies derived from the strength-duration functions for the NTS or NRV were both approximately 170 microseconds, indicating that the antinociceptive effects in these regions may not be exclusively due to the stimulation of fibers of passage. These results are discussed in terms of the role of the NTS, NRV, and caudal medulla in the modulation of nociceptive responses and cardiovascular function. PMID- 2234993 TI - Leakage of fluid administered epidurally to rats into subcutaneous tissue. AB - Epidural catheters were implanted in rats under halothane/nitrous oxide anaesthesia. Contrast medium (Iopamidol) was injected via the catheter under fluoroscopic control 24-48 h after implantation. In 15 of 20 rats contrast could be seen leaking out of the epidural space, usually after only 25 microliters was administered. Leakage was associated with diminished antinociceptive response to morphine administered via the catheter. Both leakage and decreased response to morphine could be largely prevented by applying a drop of Supa-Glue over the site of entry of the catheter to the epidural space at the time of catheter implantation. Investigators using epidurally cannulated rats should document that leakage does not occur or discard results from rats showing evidence of leakage. PMID- 2234994 TI - Clinical judgments in pain management. AB - From research reports published over the last 20 years, it appears that moderate to severe uncontrolled pain may be the norm for hospitalized patients despite recent advances in the management of pain. Research on the extent of under management of pain and the factors associated with it is examined and summarized in this paper. Methodological imperfections of the research are identified. Several explanations for pain under-management have been proposed and these are reported. A clinical decision making model is also reviewed and it is suggested that this model could be applied to pain management problems. Further, it is suggested that this model may be very useful in developing educational interventions to improve health practitioners' clinical skills in pain management. PMID- 2234995 TI - Evaluating the efficacy of EMLA in alleviating pain associated with lumbar puncture; comparison of open and double-blinded protocols in children. AB - Potential benefit of the topical anesthetic EMLA prior to lumbar puncture was studied in children with cancer. Comparison was made between 2 types of study: the first one involved 10 children who were enrolled in a double-blind placebo controlled study and in the second, 18 children in an open crossover study. Although both studies suggested the favourable effects of EMLA in alleviating pain associated with LP, they illustrated the need to perform such studies in a controlled blinded fashion; the effect in the double-blind study was not apparent in some cases, whereas it was clear cut in all open cases. PMID- 2234996 TI - Low dose amitriptyline in chronic pain: the gain is modest. AB - In the double-blind placebo-controlled study presented here, the effects were investigated of a low dose of amitriptyline (75 mg) in patients with chronic pain of various origins. The active drug was superior to placebo in reducing pain intensity. The reduction was small. In the second treatment week, the amitriptyline treated patients slept longer. No differences between active drug and placebo were found with respect to daily activities or use of analgesics. Based on our data and those of other studies, it is concluded that amitriptyline (and other antidepressants) in low doses does have a positive effect on the intensity and some other aspects of chronic pain, but that the effect is modest. It must be kept in mind that chronic pain is a very treatment-resistant condition. Therefore, even modest positive effects may be worthwhile. PMID- 2234998 TI - A genetic factor in the reaction of rats to peripheral nerve injury. PMID- 2234997 TI - Pain relief achieved by transcutaneous electrical nerve stimulation and/or vibratory stimulation in a case of painful legs and moving toes. AB - A patient is described with painful legs and moving toes. The pain had been occurring for more than 15 years, and a variety of therapies had been attempted with only partial, if any, success. Only morphine had succeeded in relieving the pain, but it had to be discontinued to avoid tolerance and dependence. We devised a treatment consisting of transcutaneous electrical nerve stimulation (TENS), vibratory stimulation (VS), and a combination of the two methods (TENS + VS). TENS brought about partial pain relief, but was less effective than VS; dual stimulation (TENS + VS) led to complete alleviation of the pain. Four months later, the patient was applying dual stimulation himself at home and was thus able to maintain complete relief with 3 or 4 weekly sessions. We suggest that dual stimulation results in a large-scale recruitment of large-diameter afferent fibres and may thus set up a powerful inhibitory control of nociception in our patient. PMID- 2234999 TI - Heritability of symptoms in an experimental model of neuropathic pain. AB - Male and female rats underwent transection and ligation of the sciatic and saphenous nerves, and the development of autonomy was monitored. The deafferented animals were then interbred, always selecting males and females that expressed relatively high and, alternatively, relatively low levels of autotomy. Offspring were similarly operated and interbred. By the sixth generation of selective breeding, lines were achieved in which autotomy was consistently high (HA) or consistently low (LA). There was no indication of sex linkage. Thermal and mechanical nocifensive responsiveness co-selected with propensity to express autotomy following nerve injury: response thresholds were lower in HA than in LA rats. F1 hybrids formed by crossing homozygous HA and LA animals showed low levels of autotomy, similar to LA stock. This indicates recessive inheritance of the autotomy trait. Backcrossing F1 hybrids onto the LA line yielded a low autotomy phenotype in almost all cases; backcrossing F1 hybrids onto HA stock yielded about 50% high autotomy and 50% low autotomy. These ratios are consistent with simple mendelian inheritance of a single gene. Taken together, the data suggest that autotomy is inherited as a single-gene autosomal recessive trait. PMID- 2235001 TI - [Principles and histologic effects of the treatment of hypertension with focused high-intensity ultrasound]. AB - Focused high-intensity ultra-sound is used to treat glaucoma. Histopathologic examinations of rabbit and pig eyes following therapeutic ultrasound demonstrated highly localized lesions including destruction of the ciliary epithelium and thinning of the sclera. The bond between the sclera and the ciliary epithelium is weakened. The conjunctiva remains intact. The histologic findings in human eye enucleated after ultra-sound therapy are identical. Three mechanisms for pressure reduction are proposed: transscleral outflow of aqueous humor can occur under the overlying conjunctiva; focal destruction of the ciliary epithelium can reduce aqueous production; scleral scarring produces the potential for separation of the ciliary body and the sclera. PMID- 2235000 TI - Adrenal medullary implants in the rat spinal cord reduce nociception in a chronic pain model. AB - Previous work in this laboratory has indicated that the transplantation of adrenal medullary tissue into the subarachnoid space of the rat spinal cord can reduce pain sensitivity to acute noxious stimuli, particularly following stimulation by nicotine. This most likely results from the stimulated release of opioid peptides and catecholamines from the transplanted chromaffin cells. However, chronic pain models may more closely resemble human clinical pain, and the arthritic rat model has been used for screening potential therapeutic strategies. The purpose of the present study was to assess the potential for adrenal medullary tissue implanted into the spinal subarachnoid space to alleviate chronic pain. Adrenal medullary tissue was implanted into adjuvant induced arthritic rats, and changes in body weight and vocalization responses were monitored over the 10 week course of the disease. Results indicate that the severe weight reduction normally associated with this inflammatory arthritis was attenuated by adrenal medullary, but not control, implants. In addition, vocalizations were reduced in animals implanted with adrenal medullary, but not control tissue following nicotine stimulation. This reduction was blocked by the opiate antagonist, naloxone, and partially attenuated by the alpha-adrenergic antagonist, phentolamine. Together, these results suggest that the transplantation of adrenal medullary tissue into the subarachnoid space of the spinal cord may provide a local source of opioid peptides and catecholamines for the reduction of chronic pain. PMID- 2235003 TI - [The treatment of failed trabecular surgery in glaucoma with ultrasound (Sonocare)]. AB - We have treated 62 recently post-operative eyes with non functioning trabeculectomies at the site of the failed bleb with one to four ultrasound applications each of five seconds duration and at an intensity level of 10 kw/cm2; 32 eyes were phakic, 7 aphakic, and 23 pseudophakic (anterior or posterior chamber). The two groups of patients showed the best response when the ultrasound treatment was performed three to twelve weeks after the last trabeculectomy; 82% are success in the phakic group, and 68% in the aphakic or pseudophakic group after three months. After the ultrasound treatment, 5FU subconjunctival injections seem to be effective in the very bad cases with a low rate of complications. PMID- 2235002 TI - [Indications and results of Sonocare (ultrasound) in the treatment of ocular hypertension. A preliminary study of 395 cases]. AB - The Sonocare system CST 100 provides high-intensity focused ultrasound to lower the intraocular pressure by three different mechanisms: partial destruction of the ciliary epithelium, scleral thinning allowing transcleral outflow of aqueous humor, and mainly the ciliary body separation from the sclera. Initially it was used to treat blind eyes with painful elevated intraocular pressure; now the indications are gradually extended to eyes with good vision. This technique takes place between laser trabeculoplasty and filtering surgery. The first 395 cases which were treated with ultrasound these two last years in the Quinze-Vingts Hospital, are displayed in this report. PMID- 2235004 TI - [An anterior chamber-subtenonian drainage tube. A long-term study]. AB - A drainage of aqueous humor from the anterior chamber to the subtenonian space using a tube and a scleral implant was performed in 22 eyes, previously unsuccessfully operated on for glaucoma. The results after a follow up of 12 to 36 months were good, specially in cases with undissectable conjunctiva (a 73% rate of success). The small incidence of serious complications incites us to use this technique earlier in the surgical treatment of uncontrolled ocular hypertension. PMID- 2235005 TI - [The value of inferior trabeculectomy in combined cataract-glaucoma surgery. Apropos of 54 cases]. AB - In 54 consecutive cases of glaucoma triple procedure, a trabeculectomy was systematically performed at six o'clock. By separating the order and the locations of the incisions as well as their placement in limbo-corneal sites, haemorrhages are minimized. A watertight, controlled running suture avoids post operative flat anterior chamber, and permits rapid tonometric normalisation. The results of these first cases are: a mean post-operative ocular pressure (O.P.): 15.1 mmHg, mean drop of O.P.: 36%; tonometric normalisation and visual-functional improvement above 90%. PMID- 2235006 TI - [Early postoperative campimetric outcome after trabecular surgery of chronic advanced glaucoma]. AB - The authors report about the results of a preliminary study concerning the changes of glaucomatous visual field just after glaucoma filtering surgery in patients with advanced glaucoma. The visual field was established preoperatively, then 7 and 30 days in post operative period. Mesopic campimetry had been selected because of its precision for central field defects. The results appear to be favourable with 13 improvements 14 stabilizations, and 7 aggravations without loss of central vision. The authors have tried to determine predictive risk factors. The most important one are preoperative campimetric shape, angle anatomy, refraction and cardiovascular diseases. PMID- 2235007 TI - [Aqueous humor flow measured by fluorophotometry. A comparative study of the effect of various beta-blocker eyedrops in patients with ocular hypertension]. AB - A randomized double-blind study of aqueous humor flow and intraocular pressure measurements before and four hours after instillation of placebo and beta-blocker eyedrops, was carried out in 40 hypertensive patients. The treated and non treated patients either did or didn't show an optic disc excavation and a visual field defect. Hypertensive patients with a previous tension treatment will stop therapy on a 3-week period up to an increase of their own ocular tension value greater than or equal to 3 mmHg. The intraocular pressure statistically decreased of 20.8% four hours after topical placebo, the aqueous humor flow remaining unchanged. In this study, timolol eyedrops induced a greater decrease of the aqueous humor flow (39%), followed equally by betaxolol (23.8%) and carteolol (20.42%). Timolol and betaxolol eyedrops equally induced a significant decrease of the intraocular pressure. There was no effect of carteolol on the intraocular pressure. The outflow facility was independent of the instilled beta-blocker eyedrop. PMID- 2235008 TI - [2 fluorophotometric methods of measuring aqueous humor flow in hypertensive patients]. AB - Two fluorophotometric methods, by instillation and oral route, allowed the aqueous humor flow measurement and apparent outflow resistance calculation in normal and hypertensive subjects. There was no statistically significant difference between the two methods in the aqueous humor flow of hypertensive patients and normal subjects. On the contrary, there was an increase of the outflow resistance in hypertensive patients in relation to normal subjects. Finally, oral route fluorophotometry allowed the individualization and calculation of a coefficient of aqueous humor production from the iris, which is statistically increased in hypertensive in comparison with normal subjects. Subsequent studies thanks to this fluorophotometric method by oral route, which interest is certain in treated hypertensive patients, should allow to determine the action site of the drug and to quantify its efficiency. PMID- 2235010 TI - [The value of electroretinography in uveitis]. AB - The involvement of the retina in the inflammation being one important factor in severe uveitis, the authors have tested the "ganzfeld" electroretinogram (ERG) in various forms of uveitis, especially in cases having opaque media. In Fuchs' syndrome and chronic anterior uveitis, the ERG is normal or only slightly altered, while important reduction of the potentials can occur even in case of good vision in intermediate uveitis, probably indicating concomitant retinal vasculitis. In Behcet's disease, ERG is mostly useful in testing the efficacy of therapy. ERG can be rather deceiving in idiopathic vasculitis, where the potentials are not always as reduced as expected. On the contrary, this test seems to allow differential diagnosis between Harada's disease and acute multifocal placoid pigment epitheliopathy. However, one must bear in mind that concurrent steroid treatment can elevate the amplitude of the potentials, a phenomenon which has to be taken into account when interpreting ERG results. PMID- 2235009 TI - [Study of the postoperative uveal reaction using the laser flare-cell meter]. AB - Aqueous flare and cells can be quantified by a new system, the laser flare-cell meter (KOWA FC 1000). Mydriasis does not influence the results, that can positively be compared to fluorophotometry. It is possible to precisely measure the surgical trauma, and inflammatory diseases of the eye. PMID- 2235011 TI - [Functional evaluation of the corneal endothelium using anterior segment fluorophotometry]. AB - The AA have studied the permeability of the corneal endothelium by anterior segment fluorophotometry using instillation of fluorescein. The Fluorotron Master TM has been modified with the introduction of a new slit (58.4 microns) and of the voltage output (6.5 v) has also been increased. The resolution has been improved from 2.39 mm to 0.59 mm. Of this study, we have examined 20 patients submitted to extracapsular cataract extraction with intraocular lens implantation (ECCE + IOL). The patients have been divided in two groups, according to the surgical technic used: "can-open" and intracapsular. Each patient have been submitted before surgery and 1 week after to an ophthalmologic examination, paquimetry and anterior segment fluorophotometry. The permeability coefficient (PAC) increases with the duration of surgery and when using "can-opener" instead of endocapsular. PMID- 2235012 TI - [Intra-corneal lens implantation: an experimental study in rabbits]. AB - After the theoretical analysis, the authors describe the experimental results of hydrogel intracorneal lenses in the rabbit stroma. PMID- 2235013 TI - [Epithelial and stromal healing after radial keratotomy. Scanning electron microscopy analysis]. AB - A study of corneal healing after radial keratotomy was conducted under scanning electron microscopy in 28 papio-papio baboons. The appearance of the incisions after follow-ups ranging from one hour to three and a half years postoperatively permits to emit some hypotheses regarding the precise mechanisms of action of radial keratotomy, as well as those governing any functional or anatomical complications susceptible to occur after the operation. PMID- 2235014 TI - [A histologic study 7 months after radial keratotomy in a 32-year-old man]. AB - A 32 years old patient died seven months after a radial keratotomy. The histologic study of one cornea is realized. The wound of anterior stroma varies from 0.08 to 0.13 mm; it is filled of epithelial cells with eosinophile cytoplasm and a round nucleus. Near this epithelial ingrowth Bowman's membrane is interrupted and the fibres of stroma lose their parallel direction in comparison with the epithelial plane. These histopathologic results are compared with the other publications; and in reference with the mechanism of the healing, an histogenesis of the corneal healing is proposed. PMID- 2235015 TI - [A comparative study of extra-capsular extraction and intra-capsular extraction with implants after 24 months' follow up]. AB - This statistical study follows the one already made in 1987 on a series of 200 patients, 150 of them have been properly analysed after 24 months. It shows that after this delay the ECCE gives an efficient protection against complications especially in regard of central and peripheral retina. PMID- 2235016 TI - [The examination of color vision using a 2 metameric equation method]. AB - Modern anomaloscopes with four independent light channels (i.e. Besancon Anomalometer which was presented in 1979 at the SFO Congress) allow accurate examinations of color vision. In our routine clinical examination, we use two metameric equations: the red-green Rayleigh equation and the blue-green Moreland equation. This so called Two-Equation-Method enables the diagnosis of congenital and acquired color vision defects in a precise qualitative as well as quantitative way. For both equations the goal of the examination is to measure the absolute matching range. Abnormal color vision is diagnosed if the absolute matching range is shifted and/or enlarged in one or both of the two metameric equations. In congenital colour vision deficiencies, the results are similar to those obtained with the Nagel anomaloscop. The different types of acquired defects are compared with the types of Verriest's classification. A computer controlled clinical examination of color vision, which will make the procedure simplier and shorter for the patient is actually being developed. PMID- 2235017 TI - [500 visual acuity tests in infants with Teller acuity cards]. AB - Assessment of visual resolution with Teller Acuity Cards is now routine procedure in infant visual check-up. A grating is printed on one end of a card on an homogeneous background of the same mean luminance. A series of spatial frequencies at an interval of one half octave covers the range of infant acuity. Binocular and monocular acuities have been measured on 517 infants between 100 and 399 days of age. The cards can be used from a few weeks of age up to 18 months at least. Then it gets more chancy to keep the child attentive. Binocular and two monocular tests take 6 minutes with a normal child. Binocular grating acuity normally reaches 6.5 cycles/degree at 4 months of age, and 12 c/deg at 12 months. Monocular acuity is one half octave lower. From the level of acuity obtained and observation of the behaviour, amblyopia can be detected and low vision can be estimated easily in infants. PMID- 2235018 TI - [Aniseikonia. A clinical study of 51 unilateral pseudophakic patients and practical applications]. AB - The subjective aniseiconia was measured with spatial eiconometer on 51 isometropic and unilateral pseudophakic patients in relation with the post operative anisometropia. The median value of subjective aniseiconia is 2-3% for anisometropia minus or equal to 5 diopters, without statistic correlation, related to a probably "sensorial brain adaptation". So error of intra-ocular lens power calculation less than 7.5 diopters may be accepted. PMID- 2235019 TI - [A new evaluation system of 3D vision]. AB - 3D vision assessment depends on monocular and binocular factors. In ophthalmology, it is clinically evaluated through the optometric examination which is not exhaustive according to the monocular elements and doesn't take on the visual stimulus quantification. The video and electro-optic displays can meet all these exigencies. The basic principles they share are exposed and then an illustration is given of their performance and their adaptation to the physiologic mechanisms. So is presented a study on the fusion area of heterophoric subjects depending on the stimulus spatial frequencies (the synthetic precisely quantified images shown were circular DOGs). This area is greatly modified following the variety of subject's heterophoria. PMID- 2235020 TI - Epidemiology of spinal cord lesions in Denmark. AB - Denmark has a population of about 5.2 million. The rehabilitation of spinal cord injured (SCI) takes place in two specialised rehabilitation hospitals. The incidence of new traumatic SCI admitted to these hospitals in the period 1975 1984 was 9.2 per million per year. During this period 92 Danes with non-traumatic and 268 with newly sustained traumatic spinal cord lesions were admitted to the rehabilitation hospital in Hornboek, which uptake area corresponded to South and East Denmark and Greenland and the Faroe Islands. Among the traumatic SCI 47% were due to traffic accidents, 23% to falls to a level below, 8% to attempted suicides, 6% to shallow water diving, and 6% to sporting accidents. The number of SCI caused by traffic accidents was found to decrease coincidently with the introduction of general speed limits and compulsory seat belt wearing. The male/female ratio was for the traumatic SCI 3.3, which was significantly lower than in the preceding 10-year period. 40% of all traumatic SCI were sustained at 15-24 years of age, and 51% had tetraplegia. Traffic accidents gave rise to more cervical, and falls to more caudal lesions. 41% of the traumatic SCI had an improvement in their neurological status after their admission to the neurosurgical department until the discharge from the rehabilitation hospital. Those with incomplete lesions showed greater improvement than those with complete lesions regardless of the level. Complete cervical lesions had significant better remissions than complete thoracic/lumbar lesions. PMID- 2235021 TI - Bone and soft tissue injuries in post-mortem lumbar spines. AB - A histological study of transverse sections of lumbar facet joints from 36 lumbar spines of subjects dying from serious trauma revealed injuries not visible on standard radiography, and in a high percentage of joints. They include fractures of the superior articular process, central infractions of the subchondral bone plate, and tears of the articular capsule, including the ligamentum flavum. The facet joint injuries in young subjects were almost entirely absent from the facet joints of a comparable group of young subjects with no recent history of major trauma. The injuries resemble some of the 'age changes' seen in older subjects dying non-violent deaths. It is suggested that such injuries may lead to early onset facetal arthritis in survivors of major trauma. PMID- 2235022 TI - A comparison of past and future leisure activity participation between spinal cord injured and non-disabled persons. AB - Leisure activity profiles of 81 male and 21 female SCI subjects were compared with profiles of 135 male and 151 female non-disabled individuals. These profiles, derived from the Leisure Activities Blank (McKechnie, 1985), revealed that SCI subjects had been more physically active (prior to injury) than those in a non-disabled comparison group; however, their post-injury expectations for future leisure activity involvement were considerably lower than a similar study of non-disabled individuals. These reduced expectations were found for both active and sedentary activity categories. It is suggested that awareness of pre morbid leisure activity profiles, plus recognition that post-injury expectations for leisure activity participation are often reduced, could assist medical personnel to prescribe treatment or offer programmes that enable SCI patients to maintain their pre-morbid lifestyles and enhance future leisure activity expectations. PMID- 2235023 TI - Late asystole in high cervical spinal cord injury: case report. AB - A patient with delayed episodes of extreme bradycardia, asystole and syncope occurring 5 to 9 weeks after traumatic high cervical spinal cord injury is described. Temporary transvenous ventricular pacing followed by oral propantheline was required to prevent further episodes. The investigation, physiology and treatment of this arrhythmia in tetraplegia are discussed. PMID- 2235024 TI - The locked-in syndrome and related states. PMID- 2235025 TI - Early intermittent self-catheterisation after spinal cord injury. AB - An evaluation has been made of intermittent self-catheterisation (ISC) carried out by 25 paraplegic patients early after injury. The results were compared with those of intermittent catheterisation (IC) done in another 48 paraplegic patients by a catheter team. No significant difference was found regarding the rate of urinary infection or the incidence of urethral trauma. The final outcome of bladder training did not differ significantly between the two groups. Patients on self-catheterisation went home earlier for the weekend. Most patients and their relatives found that self-catheterisation in the early stage was easy to perform and meant a more active participation in bladder training. Early self catheterisation may help to overcome a nursing staff shortage in a busy acute spinal cord injury ward. PMID- 2235026 TI - Respiratory function in patients with spinal cord injuries: effects of posture. AB - The purpose of this study was to evaluate the respiratory function of spinal cord injuries (SCI) during different postures. Measurements were performed with a Fukuda PM 80 spirometer on 31 chronic stable SCI and 22 normal controls. Among the SCI patients, there were 12 quadriplegics and 19 paraplegics. The respiratory parameters, including forced vital capacity (FVC) and forced expiratory volume during first second (FEV1.0) were collected in each subject during supine, sitting and standing postures. The results revealed that SCI patient had impaired FVCs (p less than 0.05), the degree of impairment depending upon the level of cord injury (r = 0.81). The FEV1.0/FVC ratio of SCI was normal. For quadriplegics, the FVC during sitting and standing fell on 30 to 50% of normal values. The FVCs of paraplegics during all postures were around 80% of the predicted values. The FVC in the control group was reduced by 5 to 7% when changing postures from erect to supine. This study concludes that respiratory impairment does occur in SCI. The results obtained display a typical pattern of restrictive pulmonary impairment. The severity of the impairment is affected by the level of cord damage and is posturally dependent. PMID- 2235027 TI - Relationship between heart rate and oxygen uptake in thoracic level paraplegics. AB - In able-bodied subjects heart rate and oxygen uptake have a linear relation up to submaximal workloads. Cardiac response to exercise or physical stress is described to be under the control of the sympathetic nervous system. Various workers have claimed that the sympathetic contribution to the cardiac plexus arises between thoracic spinal cord levels T1 and T6. Paraplegics are participating in various sporting activities in increasing numbers. Theoretically, assessing the progress of physical fitness of paraplegics with lesions above T6 by monitoring heart rate alone becomes unreliable because of damage to their sympathetic system. Forty-four paraplegics with lesion levels between T3 and T10 were put through an arm cranking exercise routine with increasing power levels. Their heart rate and oxygen uptake was measured for each power level. For analytical purposes the subjects were grouped into two groups according to their lesion level. All the subjects with the lesion at T6 or above were in one group and the other group consisted of lesion at T7 or below. Almost linear relation was found between the heart rate and oxygen uptake in all subjects of both groups. The findings of this study suggest that either the sympathetic contribution comes from above spinal level T3, or the cardiac response to an increased demand in physical exercise is controlled by some other mechanism. PMID- 2235028 TI - Quality of semen after repeated ejaculation treatment in spinal cord injury men. AB - The study was designed to document the effects of regular drainage after penile vibrator stimulation on the quality of semen in SCI men. Twenty three tetraplegics and 9 paraplegics, 18 to 40 years of age and with neurological levels ranging from C4 to L1, were examined between 1 and 23 years after injury (median 2 years). None had ejaculated after the injury. Penile vibrator stimulation was tried in patients with cervical or thoracic lesions who showed reflex hip flexion on scratching the soles of the feet, 29 out of 32, and rectal electrostimulation in the remaining 3 low lesions with no reflex function in lumbar and sacral segments. The stimulation yielded semen in 29 (91%) of the men; 22 had antegrade and 7 retrograde ejaculation. Sixteen of the 22 patients with antegrade ejaculation entered a home programme of vibrator stimulation prescribed once weekly. Four to 6 months of stimulation resulted in a rise of semen volume and of fructose and acid phosphatase levels in the seminal plasma, suggesting improved function of the seminal vesicles and the prostate. The percentage of motile sperms was low both before and after the treatment period. Despite this, the total count of motile sperms per ejaculate was already high in the patient's first ejaculates compared to the laboratory normal standard, and further clearly increased after the stimulation period. A standardised functional test measuring sperm penetration capacity showed strong evidence of long term stimulation effect. It is suggested that the test is used in the assessment of fertility potential in SCI men. PMID- 2235030 TI - A new building for the oldest spinal cord unit in The Netherlands. PMID- 2235029 TI - The various types of neurogenic bladder dysfunction: an update of current therapeutic concepts. AB - Increased experience with treatment strategies developed during the last 10 years in the field of neurourology justifies an update of current therapeutic concepts. Based on a rather simple, but clinically useful, classification of detrusor sphincter dysfunction the therapeutic concepts now available for four prototypes of detrusor-sphincter dysfunction are discussed. (1) For the combination of a hyperreflexive detrusor with a hyperreflexive (spastic) sphincter, characteristic for the reflex- and the uninhibited neuropathic bladder, detrusor-sphincter dyssynergia (DSD) is still the greatest problem, and transurethral sphincterotomy is the method of choice if this situation cannot otherwise be managed. One concept is to convert detrusor hyperreflexia into hyporeflexia by adequate pharmacotherapy, which is nowadays available, and to assist or to accomplish bladder emptying by clean intermittent (self-) catheterisation (CIC) with the advantage of dry intervals in between. Japanese colleagues recommend bladder overdistension during the spinal shock phase to achieve detrusor hyporeflexia, but this procedure is rather decisive at an early stage of the disability, leaving the detrusor no chance for further rehabilitation. Another possibility is rhizotomy of the sacral posterior roots to eliminate detrusor hyperreflexia, and the simultaneous implantation of a sacral anterior root stimulator (Brindley) to achieve electrically induced micturition. From our personal experience with 12 patients this concept is ideal for female patients with unbalanced reflex bladder and otherwise uncontrollable reflex incontinence. (2) The combination of a weak detrusor with a spastic sphincter is a clear indication for CIC, as the bladder is emptied regularly, and due to the spastic sphincter, the patient stays continent as long as controlled fluid intake prohibits overflow incontinence. The implantation of an anterior sacral root stimulator is an alternative approach provided that at least weak reflex detrusor contractions are present. (3) With the combination of an areflexive or hyporeflexive detrusor and a flaccid pelvic floor, passive voiding by abdominal straining or by the Crede manoeuvre is usually recommended, but should be replaced by CIC if this mechanism of bladder emptying creates unphysiological high and dangerous intravesical pressures, or if vesico-uretero-renal reflux is present. Neurogenic urinary stress incontinence is usually associated with this type of lesion and can be successfully treated by the implantation of an artificial urinary sphincter (Scott). However in two thirds of the patients with neurogenic bladder dysfunction, additional, usually operative treatment is necessary to meet the criteria for implantation. Moreover, a 30% rate of repair operations must be accepted by patients, but is becoming less frequently required with an improved design of the device.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2235031 TI - Functional neuromuscular stimulation in 4 patients with complete paraplegia. AB - The effect of functional neuromuscular stimulation (FNS) on muscle strength and endurance was studied in 3 patients with long-standing complete injuries (T7-T12) and in 1 patient with a recent complete injury (T5). All 4 patients became strong enough to rise, stand and to walk a few steps within parallel bars. However, only 1 patient was able to walk without parallel bars (60 m). The energy demand of FNS assisted walking was measured to be more than 60% of the maximal endurance capacity of this patient. This finding partly explains the low patient acceptance of FNS. PMID- 2235032 TI - Cisapride stimulates small intestinal motility and relieves constipation in myelopathy due to cervical spinal stenosis: case report. AB - A patient with progressive spinal stenosis, paraplegia, chronic pain syndrome and simultaneous severe chronic constipation is described. Treatment with cisapride 10 mg, 4 times daily improved her condition, and this was associated with improved small intestinal motility during a 12-hour examination using a computer aided system. PMID- 2235033 TI - Wrestling causing paraplegia. AB - This report deals with 4 patients who had a spinal cord injury resulting from wrestling. The cause and the results are discussed. PMID- 2235034 TI - The use of a calcium alginate dressing in the management of decubitus ulcers in patients with spinal cord lesions. PMID- 2235035 TI - The right to die of a high quadriplegic in a developing country: case report. AB - In the north of Thailand a 21-year-old patient with a complete quadriplegia at C4 level with respiratory insufficiency was treated, including assisted respiration. The patient felt that living held nothing for him and therefore he requested at his own free will to go home and die. PMID- 2235036 TI - Halo versus Minerva--which orthosis? PMID- 2235037 TI - Sexual ability, activity, attitudes and satisfaction as part of adjustment in spinal cord-injured subjects. AB - Changes in different aspects of sexuality were investigated and related to overall quality of life and physical, psychological and social adjustment in 73 SCI subjects, who were sexually active both before and after injury. Items on sexual interest and satisfaction were treated as one composite variable, the SIS scale, measuring sexual adjustment after injury. Despite severe genital dysfunction, more than half of the subjects (57%) rated their sexual relations after injury as satisfying or at least rather satisfying. The majority continued having intercourse, although many of them more seldom than before, and about half experienced orgasm. Sexual adjustment after injury was closely and positively correlated to frequency of intercourse, willingness to experiment with alternative sexual expressions and young age at injury. Physical and social independence and a high mood level were further positive determinants of sexual adaptation after injury, whereas the neurological level and completeness of injury showed no significant correlation with sexuality. It is suggested that sexual information and counselling should be integrated in the total care of the SCI patient to reduce the negative effects on sexuality, caused by the injury. PMID- 2235038 TI - Post-traumatic syringomyelia, an update. AB - Post-traumatic and post-arachnoiditic syringomyelia is described in 31 patients from the Midland Centre for Neurosurgery and Neurology (MCNN). It is suggested that the mechanisms may be similar in the two groups and that treatment is best directed to disabling the likely filling mechanisms by opening up the cerebrospinal fluid (CSF) pathways and deliberately leaving the dura open to create an artificial meningocele. It is suggested that drainage on its own is inappropriate but that when drainage of the syrinx is chosen as an ancillary technique then syringopleural drainage may be the procedure of choice. PMID- 2235039 TI - The team approach to urinary bladder management in spinal cord injury patients: a 26-year retrospective look at the Highland View Hospital Urinary Catheter Care Team. AB - The Highland View Hospital Urinary Catheter Care Team was organised in 1962, primarily in response to the problems of increasingly drug resistant urinary infections and their complications in a chronic disease population which included patients with strokes, renal and liver failure and heart disease as well as those with spinal cord injury (SCI). When the spinal cord injury centre was formed in 1970 the team became an integral part of the service. The early problems in organising the team, its evolution into a valuable, economically viable, patient care service and its role in urological clinical research, are discussed. PMID- 2235040 TI - China's first total care unit for the spinal cord injured. AB - Before discussing China's first total care unit for the spinal cord injured, it is important, though difficult due to lack of an epidemiological study, to give the incidence of spinal cord injury in China. The only seriously conducted study of this kind was that from the Beijing Area (Spinal Cord Injury Investigating Group in Beijing, 1988). Some of the results will be presented below. PMID- 2235041 TI - Spinal cord injury care system: fifteen-year experience at the Rehabilitation Institute of Chicago. AB - A statistical study of 15 years of the spinal cord injury care system of the Rehabilitation Institute of Chicago is reported. The Rehabilitation Institute of Chicago (RIC) is the rehabilitation component of the Midwest Regional Spinal Cord Injury Care System, a collaborative programme with Northwestern Memorial Hospital and Northwestern University. Data are reported on 1382 patients, a representative sample of the over 2000 patients treated since the inception of the centre. The sample was predominantly male (83%, N = 1147) and caucasian (64%, N = 888). The most common aetiology was motor vehicle accidents (36%, N = 505). During the 15 year period there were significant decreases in both acute and rehabilitation lengths of stay. Ninety three per cent of the patients were discharged home. Rehabilitation benefits were demonstrated by improvements in the Modified Barthel Index. The research, educational and clinical programmes are described. PMID- 2235042 TI - Surgical rehabilitation of the upper limb in tetraplegia. PMID- 2235043 TI - Injuries to elite wheelchair athletes. AB - The purpose of this project was to describe the nature, type, and frequency of athletic injuries incurred by the elite wheelchair athlete. Nineteen athletes participated in a 1-year injury recall study at an elite wheelchair training camp. An injury was defined as anything the athlete expressed concern about and (a) caused a loss of participation due to an injury or illness or (b) an injury in which a fracture, dislocation, or subluxation occurred and the athlete was able to continue participation. There were 10 male and 9 female subjects who reported their injuries from 1 June 1987 to 31 May 1988. Fifty injuries were reported, strains and muscular injuries accounted for almost half of the injuries. Physicians were the primary care provider for 37% of the injuries, followed by physical therapists and athletic trainers at 26% and 15% respectively. Slightly over 57% of the injuries were classified as minor, missing 7 days or less of participation and 32% were classified as major, missing 22 days or more of participation. The upper extremity was the most frequently injured, followed by the lower extremity, head and spine, and illnesses. Conventional treatments of ice, heat, modalities, and medications, were the most common methods of treating these injuries. Flexibility and strength training programmes should be implemented throughout the competitive season. Careful consideration of the training programme and workout intensity should also be evaluated. PMID- 2235044 TI - Cotrel-Dubousset rods in spinal fractures. PMID- 2235045 TI - Intravesical electrical stimulation for the rehabilitation of the neuropathic bladder. PMID- 2235047 TI - Changes in ambulation parameters in spinal cord injury individuals following rehabilitation. AB - The energy cost and gait parameters of 10 spinal cord injury patients (mean age = 21.7 +/- 2.3 years) were measured at discharge from initial rehabilitation and at 1 year follow-up. At follow-up testing patients walked faster (59.5 m/minute vs 40.4 m/minutes; p less than 0.001), more efficiently (0.26 ml O2/kg.m vs 0.40 ml O2/kg.m; p less than 0.05) had slower heart rates (115 beats/minute vs 133 beats/minute; p less than 0.01), and required decreased axial load on upper extremity assistive devices (18% body weight vs 26% body weight; p less than 0.03). At follow-up testing, those patients with remaining weakness in the lower limbs had greater conditioning effects (increased rate of oxygen consumption and oxygen pulse) than those patients with relatively stronger limbs. These findings indicate that clinicians can expect significant improvements in functional ambulation performance in the first year following initial rehabilitation due to improved strength and conditioning. PMID- 2235046 TI - Reciprocal aided gait in paraplegia. AB - A group of 9 male paraplegics, experienced in the use of walking aids for ambulation, were tested using an alternate four-point gait. Data were collected pertaining to the axial load transmitted through the crutches, the upper limb joint displacements and the moments about the elbow and shoulder joints during the period of contact of the walking aid with the ground. This gait was found to be slow with long periods of load transmission through the walking aids. Comparatively high values were calculated for the moments about the joints of the upper limb. PMID- 2235048 TI - The Spinal Cord Injuries Center Hamburg. PMID- 2235049 TI - Differences between rehabilitation disciplines in views of depression in spinal cord injury patients. AB - Reports based on clinical impressions have suggested that depression after spinal cord injury (SCI) is a near-universal phenomenon; however, studies using objective methods and strict criteria have not confirmed this. The aim of this study was to explore the experiences and opinions of rehabilitation clinicians with the depressed mood in their SCI patients. A questionnaire was completed by 149 staff members of various disciplines working in four specialised SCI rehabilitation centres. We found that the disciplines vary in the symptomatology they observe (nurses most, physicians and mental health professionals least), and that these differences to some degree correspond to variations in the estimate of the frequency and intensity of depression in the average patient. The amount of staff experience was found not to be a factor. The implications of these findings for theories of staff expectations regarding patient mood states and the functioning of the clinical team are discussed. PMID- 2235050 TI - Obstructive disordered breathing during sleep in patients with spinal cord injury. AB - Little is known about respiration and sleep in spinal cord injured (SCI) patients, and yet they frequently have complaints related to sleep. Four SCI patients with various sleep complaints were evaluated with nocturnal polysomnography. All 4 had evidence of obstructive sleep apnea (disordered breathing). These findings suggest that obstructive sleep apnea may be contributing to disruptive sleep in SCI patients and may be responsible for many of their daytime symptoms. PMID- 2235051 TI - Neural stimulation for spinal spasticity. AB - The knowledge of neural plasticity is used to improve motor function of the spinal cord by chronic stimulation of the dorsal columns. We achieved this with an improvised technique. The electrodes are exteriorized and stimulated by using a Grass stimulator. Five paraplegic patients with different aetiologies causing their paraplegia were treated by this method, and the details are enumerated. Four had good improvement and relaxation was maintained for varying periods after cessation of the stimulation. Mode of action is discussed. PMID- 2235052 TI - Hip joint instability in an infant with paraplegia following aortic surgery. AB - A report on an infant with paraplegia following aortic surgery who suffered from coarctation of the aorta and a ventricular septum defect (VSD). The spinal paralysis was complete and flaccid. He was found to have paralytic bilateral dislocatable hip joints. Magnetic resonance image (MRI) of spinal cord showed no pathological findings. The hip joints were treated by a hip abduction brace. PMID- 2235053 TI - Techniques for lumbar discography and computed tomography/discography in clinical practice. AB - The technique for lumbar discography is not well standardized. To better understand lumbar pathology, we have developed a consistent, reproducible, and relatively simple procedure for lumbar discography. We describe our technique and discuss variables that may differ among individual lumbar discography procedures. PMID- 2235054 TI - Complications in primary total knee arthroplasty. AB - Total knee arthroplasty is one of the most popular and satisfying procedures in orthopaedic surgery. However, several perioperative and postoperative complications may follow total knee arthroplasty, leading to reconstruction failure. This article summarizes the issues of wound healing, infection, supracondylar fractures, thromboembolic disease, soft tissue balance, peroneal nerve palsy, and patellofemoral problems following primary total knee arthroplasty. PMID- 2235055 TI - Treatment of comminuted distal radial fractures with preliminary horizontal finger trap traction and a Roger-Anderson external fixation device. AB - Over a five-year period, 43 patients with comminuted distal radial fractures were treated with a Roger-Anderson external fixation device after the fracture was aligned in Strong's horizontal finger trap traction. Nineteen patients (21 wrists) were available for personal interview and radiographic follow-up. A 0.5 mm loss of radial height and an average loss of 2.4 degrees of palmar angulation presented. Range of motion (ROM) was excellent, stiffness was nonexistent or minimal in 81%, pain was nonexistent or minimal in 86%, and weakness of grasp was nonexistent or minimal in 81%. Complications were minimal; they included three pin tract infections, two of which required pin removal before they resolved. One patient fractured a pin that also required removal. Strong's horizontal finger trap traction and the Roger-Anderson external fixation device simplified the sometimes difficult treatment of this fracture. It seems to be most effective in young athletic individuals who have good bone stock and very comminuted fractures. PMID- 2235058 TI - Tips of the trade #28. Accurate tunnel placement using drill guides in knee ligament reconstruction. AB - Knee ligament reconstruction is optimized when intra-articular grafts are placed isometrically. Several drill guides have been designed to facilitate accurate tunnel placement. The use of an intra-articular keying hole, made with a burr, enhances proper and secure drill guide placement. Sterile mineral oil lubrication of the drill guide components will help prevent their distortion and will eliminate improper tunnel placement. PMID- 2235057 TI - Arthroscopy update #8. Auxiliary portal for assessing patellofemoral alignment. AB - An auxiliary arthroscopic portal may be used to improve visualization and evaluation of the patellofemoral joint. A reusable transquadriceps tendon portal, which assesses patellar alignment within a 0 degree to 90 degrees range of motion, is described. PMID- 2235056 TI - A technique of acetabular reconstruction for uncemented total hip replacement. AB - A technique for performing uncemented total hip replacement in the presence of osteoarthritis with proximal femoral migration is detailed. The femoral head is used as an autograft. The center of rotation of the hip is returned to its anatomic location, and subchondral bone is preserved. Rigid fixation of the graft is accomplished with matching reamers and AO lag screw fixation. Simultaneous reaming of graft and host bone produces a seamless transition to ensure graft loading. The goals of restoration of anatomic hip center, rigid press fit, and complete cup coverage are accomplished. PMID- 2235059 TI - Pediatric update #15. Florid reactive periostitis of the digits. AB - Benign fibrous lesions of the digits can present a considerable diagnostic challenge. Some lesions may resemble sarcomas, resulting in needless amputation. One such benign entity resembles myositis ossificans histologically but presents as an aggressive hand lesions. Unfortunately, this lesion has been given multiple names. It is most appropriately termed florid reactive periostitis. This paper reports a case of florid reactive periostitis in a 12-year-old girl. PMID- 2235061 TI - B-chromosomes: germ-line parasites which induced changes in host recombination. PMID- 2235060 TI - Selection and evolution of virulence in bacteria: an ecumenical excursion and modest suggestion. AB - Why do parasites kill their hosts? During this past decade, research in three different areas; evolutionary ecology, medical microbiology, and population genetics has provided theory and data that address this and related questions of selection and the evolution and maintenance of parasite virulence. A general theory of parasite-host coevolution and the conditions for selection to favour parasite virulence has been put forth. Considerable advances have been made in elucidating the mechanisms of pathogenicity and inheritance of virulence in bacteria. The population genetic structure and the relationship between pathogenic and non-pathogenic forms has been determined for a number of species of bacteria. We critically review these developments and their implications for questions of selection and the evolution and maintenance of virulence in bacteria. We postulate how selection may operate on specific types of bacterial virulence and present a general protocol to experimentally test hypotheses concerning selection and the evolution of virulence in bacteria. PMID- 2235062 TI - Virulence of lizard malaria: the evolutionary ecology of an ancient parasite-host association. AB - The negative consequences of parasitic infection (virulence) were examined for two lizard malaria parasite-host associations: Plasmodium agamae and P. giganteum, parasites of the rainbow lizard, Agama agama, in Sierra Leone, West Africa; and P. mexicanum in the western fence lizard, Sceloporus occidentalis, in northern California. These malaria species vary greatly in their reproductive characteristics: P. agamae produces only 8 merozoites per schizont, P. giganteum yields over 100, and P. mexicanum an intermediate number. All three parasites appear to have had an ancient association with their host. In fence lizards, infection with malaria is associated with increased numbers of immature erythrocytes, decreased haemoglobin levels, decreased maximal oxygen consumption, and decreased running stamina. Not affected were numbers of erythrocytes, resting metabolic rate, and sprint running speed which is supported by anaerobic means in lizards. Infected male fence lizards had smaller testes, stored less fat in preparation for winter dormancy, were more often socially submissive and, unexpectedly, were more extravagantly coloured on the ventral surface (a sexually dimorphic trait) than non-infected males. Females also stored less fat and produced smaller clutches of eggs, a directly observed reduction in fitness. Infected fence lizards do not develop behavioural fevers. P. mexicanum appears to have broad thermal buffering abilities and thermal tolerance; the parasite's population growth was unaffected by experimental alterations in the lizard's body temperature. The data are less complete for A. agama, but infected lizards suffered similar haematological and physiological effects. Infected animals may be socially submissive because they appear to gather less insect prey, possibly a result of being forced into inferior territories. Infection does not reduce clutch size in rainbow lizards, but may lengthen the time between clutches. These results are compared with predictions emerging from several models of the evolution of parasite virulence. The lack of behavioural fevers in fence lizards may represent a physiological constraint by the lizards in evolving a thermal tolerance large enough to allow elimination of the parasite via fever. Such constraints may be important in determining the outcome of parasite-host coevolution. Some theory predicts low virulence in old parasite-host systems and higher virulence in parasites with greater reproductive output. However, in conflict with this argument, all three malarial species exhibited similar high costs to their hosts. PMID- 2235063 TI - The evolution of inducible defence. AB - Defences against parasites are characterized by inducible, amplifiable responses, often with a memory component. Inducible defences with similar properties are common in a variety of other types of interactions, for example many aquatic invertebrates produce inducible structural defences against their predators and competitors. Most inducible defences have the following properties: (1) a threshold of activation; (2) an amplification of response with increasing stimulus; (3) a memory component. Specificity, amplification and memory are the basis for defining a defence as 'immune' (Klein, 1982), and these properties are present in both the vertebrate and invertebrate internal defence responses to pathogens. Invertebrates differ in the absence of immunoglobulins and therefore in reduced specificity. Although the reduced specificity of invertebrate internal defence systems is often viewed as proof of their 'primitiveness', the differences in defence systems of vertebrates and invertebrates may be more related to their respective selection regimes than to phylogeny. The syngeneic recognition system of vertebrates functions to recognize small departures from self, such as would arise from neoplasia. Are vertebrates under more intense selection from neoplasia, perhaps due to a greater incidence of hormonal imbalance or hypersensitivity reactions? The invertebrate internal defence systems are all less discriminating than the vertebrate, but there are marked differences in degree of discrimination depending on whether the group is colonial or not. Even the phyla of colonial animals with quite simple body plans, the sponges and cnidarians, have a more discriminating recognition system than the phyla of solitary animals with more complex body plans, such as the molluscs and arthropods. The primary effectors of all invertebrate responses to parasites are encapsulation and phagocytosis, although in some phyla there are specific antibacterial proteins than can also be induced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235064 TI - Parasites, desiderata lists and the paradox of the organism. PMID- 2235065 TI - Genetic exchange and evolutionary relationships in protozoan and helminth parasites. AB - The study of genetic exchange systems and the use of genetic analysis has been relatively limited in parasites leading to considerable gaps in our basic knowledge. This lack of knowledge makes it difficult to draw firm conclusions as to how these systems evolved. An additional problem is also raised by the difficulties in defining evolutionary distances particularly with the unicellular protozoa, using classical ultrastructural and cytological criteria. While these difficulties have by no means been overcome, the use of rapid sequencing techniques applied to the ribosomal genes has allowed measurement of evolutionary distances, and considerable advances in our understanding of the genetic exchange systems in a few parasitic protozoa have recently been made. The conclusions from these recent sets of analyses are reviewed and then examined together in order to discuss the evolution of genetic exchange systems in parasitic protozoa. The evolutionary distances defined by ribosome sequence analysis show that parasites are an extremely divergent group, with distances which, in some cases, are orders of magnitude greater than the distances between mammals and fish; furthermore these studies suggest that the parasitic protozoa or their free-living ancestors are extremely ancient. These findings support the view that parasitism has occurred independently many times and that the parasitic life-style has been adopted by evolutionarily distinct groups. The recent observation of a non obligatory genetic system in the diploid but evolutionary ancient kinetoplastid Trypanosoma brucei suggests that diploidy and meiosis are extremely old. The observation, in parasitic protozoa and helminths, that selfing or non-obligatory mating is a common feature suggests that these processes may be strategies to overcome the cost of meiosis. In this context, the question of what selective forces maintain genetic exchange is discussed. PMID- 2235066 TI - Eimeria species: studies using rRNA and rDNA probes. AB - rRNA and a heterologous cloned rDNA probe have been used to detect the rRNA genes of Eimeria species which infect the chicken, and has allowed the isolation and preliminary characterization of cloned rDNA sequences from a genomic DNA library of Eimeria tenella. It is demonstrated that rRNA and rDNA probes can be used to identify individual Eimeria species by the restriction fragment patterns detected after Southern hybridization. In addition, studies have shown that the large and small subunit rRNAs are expressed throughout sporulation. PMID- 2235067 TI - Hymenolepis diminuta: changes in intestinal morphology and the enterochromaffin cell population associated with infection in male C57 mice. AB - Mean villus height, crypt depth and the number of 5-HT-positive enterochromaffin (EC) cells have been examined in two regions of the small intestine (20-30% and 60-70% distance from the pylorus) of male, 6 to 8-week-old, C57 mice following a 5-cysticercoid infection of the rat tapeworm, Hymenolepis diminuta. Test mice and sham-infected controls were autopsied 0, 4, 8, 10, 14 and 28 days post-primary infection (p-1 degree-i) and 2, 4, 5, 7 and 14 days post-secondary infection (p-2 degrees-i), administered 28 days p-1 degree-i. Morphometric analysis revealed a statistically significant increase in crypt depth in the 60-70% intestine region in infected mice during both primary and secondary infections; no significant deviation from the control was observed for villus height in infected mice. Statistical analysis showed a significant increase in the number of 5-HT-positive EC cells in infected mice. This response occurred in the lower portion of the intestine on days 10-p-1 degree-i and 5-p-2 degrees-i, and was not due to increased mucosal surface area in this region. Results are discussed with reference to murine cestode rejection and the possible involvement therein of the neuroendocrine system. PMID- 2235068 TI - Molecular characterization of the surface and cyst fluid components of Taenia crassiceps. AB - Information relating to the characterization of cestode surface macromolecules is limited. This is especially the case with Taenia crassiceps, a well-recognized model for the study of larval cestodiasis. Here, the protein and glycoprotein composition of the tegumental surface and cyst fluid of the metacestode have been investigated using radio-isotope labelling, immunoprecipitation, SDS-PAGE and lectin affinity chromatography. A restricted number of surface proteins was labelled with the 125I/Iodogen method although the majority were immunogenic; in contrast an array of cyst fluid antigens were labelled. Host serum proteins, including immunoglobulins, were identified on the surface and in the cyst fluid. Some of the 125I-labelled surface proteins, including a 37 kDa molecule, have been shown to be glycoproteins and probably contain-D-mannose and/or D-glucose; there is limited or no N-acetylglucosamine and no terminal galactose present on these components. A 37 kDa surface molecule, possibly the same glycoprotein, was also precipitated by infection sera and this may endorse the theory that highly immunogenic carbohydrates are continuously shed by T. crassiceps as a mechanism for diverting the immune response of the host. Radio-iodinated and biosynthetically labelled T. crassiceps antigens were highly cross-reactive with antibody raised to other cestodes and not one antigen was identified as a possible candidate for use in specific immunodiagnosis of any of the important taeniid infections. PMID- 2235070 TI - Population dynamics in echinococcosis and cysticercosis: regulation of Taenia hydatigena and T. ovis in lambs through passively transferred immunity. AB - A comparison has been made of the interactions between passively transferred and actively acquired immunity in regulating populations of Taenia hydatigena and T. ovis. When ewes were grazed prior to parturition under a high infection pressure, immunity was transferred to their offspring for up to 8 weeks. A qualitative difference between the species was the destruction of larval T. ovis prior to their establishment ('pre-encystment immunity') and that of T. hydatigena after they had become established ('post-encystment immunity') in the challenged lambs. The major difference in terms of population regulation between the two parasites was that infection occurred with T. hydatigena but not with T. ovis in those lambs reared from birth for 16 weeks under high infection pressure. Passive, like active immunity, is a density-dependent constraint. It plays an important role in the population regulation of T. ovis, but not of T. hydatigena. This is discussed in terms of transmission in the natural environment, an hypothesis on humoral protection and the need to elucidate pathways of protection when immunization schedules are being evaluated for controlling the taeniid zoonoses. PMID- 2235069 TI - The relationship between the frequency distribution of Ascaris lumbricoides and the prevalence and intensity of infection in human communities. AB - Observed field data from a range of geographically distinct human communities suggest a consistent non-linear relationship between prevalence and mean intensity of Ascaris lumbricoides infection. Utilizing the negative binomial distribution as a description of observed aggregation, maximum-likelihood analysis reveals that the degree of aggregation is a negative linear function of mean worm burden. The factors responsible for this relationship in human populations require further study but may involve some combination of (i) density dependent reduction in worm numbers within individuals, (ii) density-dependent parasite-induced host mortality or (iii) self-treatment by heavily infected hosts. Variability in the degree of aggregation appears dependent on the level of infection in a community and independent of geographical differences in the host or parasite populations. PMID- 2235071 TI - The laboratory maintenance of Diphyllobothrium dendriticum (Nitzsch, 1824). AB - A protocol for the routine laboratory maintenance of the life-cycle of Diphyllobothrium dendriticum, using herring gulls (Larus argentatus), Cyclops abyssorum and rainbow trout Oncorhynchus mykiss ( = Salmo gairdneri) as the definitive, first and second intermediate hosts respectively, is described. PMID- 2235072 TI - Speciation of echinostomes: evidence for the existence of two sympatric sibling species in the complex Echinoparyphium recurvatum (von Linstow 1873) (Digenea: Echinostomatidae). AB - Evidence for the existence of 2 first intermediate host-specific sibling species of the 45 collar-spined echinostome Echinoparyphium recurvatum is presented. Experimental studies on their life-cycles were carried out under controlled laboratory conditions. The two entities were found to be morphologically indistinguishable in all major respects, yet they exhibited distinct biological characteristics. One of the sibling species utilizes the freshwater lymnaeid pulmonate snail Lymnaea peregra as first intermediate host, and the adults occur in the anterior small intestine of the wildfowl experimental definitive host Anas platyrhynchos. The other utilizes the freshwater mesogastropod prosobranch snail Valvata piscinalis as first intermediate host, and the adults occur in the posterior small intestine and rectum of A. platyrhynchos. The existence of the two sibling species in sympatry may be explained by the fact that the life-cycles of the two forms represent two distinct cycles of transmission serving to reduce excessive competition between them. PMID- 2235073 TI - The influence of second intermediate host dispersion pattern upon the transmission of cercariae of Echinoparyphium recurvatum (Digenea: Echinostomatidae). AB - Transmission of cercariae of the echinostome digenean Echinoparyphium recurvatum was observed in experimental populations of the second intermediate host snail Lymnaea peregra. Populations of 100 snails were distributed among plastic mesh cages in an infection arena to produce different patterns of host dispersion. Cercarial transmission was investigated in host populations showing three separate patterns of host dispersion; Ideal Regular, Random and Contagious ('Clumped'). Levels of cercarial transmission in populations showing each type of dispersion pattern were found to be significantly different. The highest rate of cercarial transmission occurred in the contagiously dispersed host population, and the lowest in the randomly dispersed population. Analysis of results from the randomly dispersed population also showed that both the mean percentage prevalence of infection, and also the mean number of cysts recovered per snail, increased significantly with the number of snails per cage. The positive relationship between the mean number of cysts per snail and the number of snails per cage was found to be best described by an exponential function. Chemosensory location of L. peregra snail hosts by E. recurvatum cercariae may provide an explanation for the patterns of cercarial transmission observed. PMID- 2235074 TI - A comparison of multiplication rates in primary and challenge infections of Trypanosoma brucei bloodstream forms. AB - The hypothesis that division of Trypanosoma brucei slender bloodstream forms is dependent upon the availability of a host-derived growth factor has been tested by superimposing challenge doses of slender-form trypanosomes onto preexisting infections at a time during the primary infection when stumpy forms predominated. The challenge populations grew in the doubly-infected mice indicating that depletion of a putative growth factor by the expanding population of the primary infection had not prevented division of the trypanosomes although slight reductions in multiplication rates were observed. This effect was independent of the variable antigen type (VAT) of the trypanosomes and of their stock of origin. PMID- 2235075 TI - Proteolytic activity in Tritrichomonas mobilensis. AB - Cell extracts of an entero-invasive protozoon of squirrel monkeys, Tritrichomonas mobilensis, contained relatively high proteolytic activity, measured on hide powder azure (HPA). Multiple proteinase forms, optimally active at pH 5-7, were detected by electrophoretic analysis in gelatin-containing polyacrylamide gels. Three major proteinase bands of apparent low molecular weights, Mr 18, 23 and 30 kDa, were seen on gels. Inhibition-activation studies suggest that only cysteine proteinases were involved in HPAase and gelatinolytic activities of T. mobilensis cell extracts. PMID- 2235076 TI - The influence of genes mapping within the major histocompatibility complex on resistance to Trichuris muris infections in mice. AB - Two panels of H-2 recombinant strains of mice were used in an attempt to map the H-2-linked genes which control resistance to infection with Trichuris muris. Response phenotypes could be related to the presence of 'resistance' (q,b) or 'susceptibility' (k,d) alleles at I-A. The influence of these genes was modulated by other alleles, particularly q or d alleles, at the D end of the H-2. Absence of I-E molecules correlated with resistance to infection in some but not all strains studied. Thus the (B10.BR x B10.G) F1 strain which expressed I-Ek gene products was resistant to infection. A study of the time-course of infection in strains of mice expressing q alleles throughout the H-2 on 4 different genetic backgrounds (NIH, SWR, DBA and B10) revealed that most strains were resistant to infection. However, the DBA/1 strain exhibited differential responsiveness, 4 out of 6 individuals harbouring mature adult parasites on day 35 post-infection. PMID- 2235077 TI - Immunogenetic correlates of susceptibility to infection with Heligmosomoides polygyrus in outbred mice. AB - Outbred MF1 mice were characterized with respect to their susceptibility to infection with Heligmosomoides polygyrus (Nematoda) on the basis of faecal egg counts after 8 weeks of repeated infection (50 larvae/week). Selective breeding for resistance and susceptibility was carried out over 3 generations. The H-2 type of a sample of the mice was determined, and antigen recognition assessed on the basis of Western blots against adult and larval H. polygyrus homogenate. The selective breeding programme yielded very strong evidence for the heritability of susceptibility to infection. The results were consistent with a model of single gene control with resistance dominant over susceptibility. The presence of the H 2k haplotype was significantly associated with susceptibility, as was the recognition of a 17 kDa antigen in blots against both larval and adult worm homogenate. The proportion of mice phenotypically susceptible to infection, the proportion bearing the H-2k haplotype, and the proportion recognizing the 17 kDa antigen, were all approximately 0.25. PMID- 2235079 TI - An experimental and theoretical study of the dynamics of a mouse-nematode (Heligmosomoides polygyrus) interaction. AB - The population dynamics of outbred laboratory mice in indoor enclosures in the absence and presence of a naturally transmitted direct life-cycle nematode Heligmosomoides polygyrus Dujardin 1845 were reported previously. This manuscript presents further information on the age and sex structure of the populations, results of experiments designed to estimate the density-dependent effect of the parasite on host survival and reproduction, and a mathematical model of both uninfected and infected mouse populations. In the uninfected mouse population, survival of female mice was age- and density-independent, survival of male mice was age-dependent and density-independent, and recruitment was density-dependent. Independent experiments revealed that the parasite had no density-dependent effect on mouse reproduction, but had density-dependent effects on both acute and chronic survival of mice. An age-structured Leslie matrix model captured the exponential growth and plateau of the uninfected mouse population. Modification of the model to incorporate the effects of the parasite provided a good fit to the data from the infected populations, supporting the hypothesis that density dependent effects of the parasite on host survival could lead to regulation of host abundance. PMID- 2235078 TI - Intracellular differentiation of Leishmania amazonensis promastigotes to amastigotes: presence of megasomes, cysteine proteinase activity and susceptibility to leucine-methyl ester. AB - Intracellular differentiation of Leishmania promastigotes to amastigotes is a critical step in the establishment of infection. In this report three related features of mexicana subspecies amastigotes were used to follow the differentiation of the parasites within macrophages. Early after infection, (a) parasites did not contain ultrastructurally recognizable megasomes, (b) cysteine proteinase activity of parasite lysates was not detected in gelatin-containing acrylamide gels, and (c) parasites were essentially resistant to L-leucine-methyl ester (Leu-OMe). Typical megasomes were first identified on the 5th day, were more prevalent on day 7, and underwent swelling in macrophages exposed to Leu OMe. Cysteine proteinase activity was first detected on day 3 and increased thereafter. Susceptibility to Leu-OMe of parasites studied in situ or isolated from infected macrophages increased with time of intracellular residence and by 7 days approached that of amastigotes isolated from mouse lesions. In contrast, parasites derived from either promastigotes or amastigotes were equally susceptible to another leishmanicidal compound, tryptophanamide (Trp-NH2). The results provide additional support for the involvement of megasomes and their cysteine proteinases in parasite killing by Leu-OMe, and highlight the slow pace of the intracellular differentiation of L. amazonensis promastigotes to amastigotes. PMID- 2235080 TI - Capture and penetration processes of the free-living juveniles of Trichostrongylus colubriformis (Nematoda) by the nematophagous fungus, Arthrobotrys oligospora. AB - The nematode-trapping fungus Arthrobotrys oligospora traps and invades all the free-living juvenile stages of the trichostrongyle nematode Trichostrongylus colubriformis. The processes of capture and invasion of the 1st-stage juveniles are described using differential interference contrast optics and 3-D reconstruction techniques. The adhesive responsible for capture is well preserved using a freeze-substitution technique for scanning electron microscopy. The invasion process of the ensheathed 3rd-stage juvenile of T. colubriformis takes much longer than in the 1st- or 2nd-stage juvenile and involves the formation of secondary infection pegs between the sheath and the cuticle which appear to penetrate the cuticle by physical pressure. PMID- 2235081 TI - [Ataxia telangiectasia: a model of investigation of chromosomal translocations]. PMID- 2235082 TI - [Platelet antibody activity in malaria thrombocytopenia]. AB - To assess immune responses to malaria-induced thrombocytopenia, an haematologic and immunologic study was performed on 25 patients with imported malaria upon admission and 8 days after treatment. Thrombocytopenia (150 x 10(9)/litre) was detected in 19 cases (P. falciparum: 11 cases, P. ovale: 6 cases, P. vivax: 2 cases). No laboratory evidence of disseminated intravascular coagulation impairment was found in any of the patients. Bone marrow examination performed in 9 cases showed no abnormality in the megakaryocyte series. Platelet count was independent of circulating parasite levels (r = 0.27) and inversely related to the number of antibody binding sites (ABS) on platelets (r = -0.6, p. less than 0.01). The indirect Coombs test (r = -0.54; p less than 0.01) and IgG and IgE levels (p less than 0.02) gave similar findings. A statistical correlation was observed between the level of circulating immune complex and the number of ABS (r = 0.525, p less than 0.01). Thus malaria-induced thrombocytopenia seems to mainly involve IgG type antiplatelet antibody activity. Although they may be implicated in the binding of antibodies to platelets, circulating immune complexes do not appear to mediate thrombocytopenia. PMID- 2235083 TI - [Hourly serum cortisol assay over 24hr by immunoenzymology in depression]. AB - Enzymoimmunoassays have been developed as alternatives to radioimmunoassays because they obviate the need for labelled compounds yet offering comparable specificity. The authors used an enzymoimmunoassay to investigate hourly serum cortisol levels over 24 hours in 6 patients (aged over 40 years) with endogenous depression (4 unipolar depressions, under antidepressor treatment and 2 bipolar depressions, without medication) and in 2 controls, aged 20 and 47 years. In agreement with literature data, a clear circadian rhythm was observed in controls and in the depressed patients, and hypercorticism was noted in one depressed patient. A trend towards phase advance in depression was seen in both the treated and untreated patients. PMID- 2235085 TI - [Identification of Campylobacter jejuni by using a biotinylated probe]. AB - A DNA biotinylated probe for the rapid identification of Campylobacter jejuni in culture (Enzo Biochem, New York) has been evaluated. The hybridized biotinylated DNA probe is detected by its interaction with streptavidin linked to horseradish peroxidase. Sixteen strains of C. jejuni, including type strain. 24 strains of other Campylobacter and Helicobacter species, and 59 strains of other general have been studied. The probe was highly sensitive (100%) and specific (100% inside the genera Campylobacter and Helicobacter). All Campylobacter strains gave strong signals, and only three weak signals have been observed with non Campylobacter strains. Our results indicate that specific recombinant DNA probe should offer a reliable and rapid method for routine diagnosis of Campylobacter jejuni enteritis. PMID- 2235084 TI - [Prevalence of hepatitis B (Hbs Ag, Hbe Ag, DNA) and delta virus markers, in about 10,000 pregnant women in Limoges (France)]. AB - The risk of perinatal B virus transmission is well known, but is estimated in France on results obtained from blood donors or from urban populations. In the present study, the screening of HBs Ag was carried out during five years (1984 1988), within a sample population of pregnant women (french women: 8,364, immigrant women: 1,206) seen in the university hospital of Limoges. Positive sera for HBs Ag were also tested for the other markers of B virus including specific DNA, and markers of the delta virus. The total seroprevalence of HBs Ag among these women was 0.54%, and was significantly higher in the immigrant women group (2.57%) when compared to that of french women (0.25%). During the same period (1984-1988), the seroprevalence among females blood donor was 0.03%. Among the HBs Ag chronic carrier pregnant women (n = 52), 27% were HBe Ag positive and four of them (31%) had viral DNA in their serum. Viral DNA was found in three women who were HBe Ag negative. Thirteen per cent of the HBs Ag positive pregnant women were infected by the delta virus. PMID- 2235086 TI - [Effect of ceftriaxone on aerobic fecal flora in children]. AB - Counts of aerobic faecal flora were done using serial dilutions of stools cultured on selective media in order to estimate the ecological effects of ceftriaxone. Twenty children were studied (24 courses of treatment), 17 of them with post-chemotherapy agranulocytosis. Enterobacteriaceae disappeared in all cases. After treatment, they rose again, unless another antibiotic was administered. No Pseudomonas could be found, due to the protective isolation. Streptococci D disappeared in 6 children. Staphylococcus aureus was present transiently at a low level in one case. Candida persisted in two cases at the same level in spite of antifungal therapy. PMID- 2235087 TI - [In vitro antifungal activity of mercurobutol]. AB - Mercurobutol, in its commercial form, exhibits fungistatic and fungicidal activities against both yeasts: Candida albicans, C. tropicalis, Torulopsis glabrata, Pityrosporum spp., and filamentous fungi: dermatophytes, Aspergillus fumigatus, mainly saprophytic or potentially pathogenic fungi of the cutaneo mucous flora. Minimal inhibitory concentrations on this antiseptic indicate a high susceptibility of the species tested, that could justify the enlargement of the indication of the drug to the complementary treatment of most cutaneous mycosis. PMID- 2235088 TI - [Proteinuria selectivity: description of a new index]. AB - An improved simple method for determination of selectivity index has been described. This new index (Creteil index) has been compared to Cameron index. The correlation between both indexes has been 0.949 (R-squared). Creteil index is a less expensive method because only two determinations are requisited in serum and urine: albumin and IgG. In Cameron index, transferrin and IgG are detected and albumin has to be measured in addition in the blood to appreciate the nephrotic syndrome. PMID- 2235089 TI - [Cancer of the breast. Genetic alterations and prognostic factors]. AB - The etiology of breast cancer is thought to involve a complex interplay of various factors, among them: genetic alterations. Multiple studies have been made to identify and characterize mutations that frequently occur during tumorigenesis. In human breast cancer, some of these alterations involve implication of proto-oncogenes (c-myc, c-erbB-2 and int-2) that have been shown to contribute to tumorigenesis by using the transgenic mouse model. Loss of heterozygoty represents the other important type of abnormalities that has been frequently observed in breast tumor DNAs; these specific genic deletions could inactivate or remove suppressor genes. In some studies, specific alterations have been associated with some clinical parameters, but have led to numerous controversies. Larger studies would be necessary to confirm some alterations as useful prognostic factors of the post-surgical course of the disease. PMID- 2235090 TI - [Norfloxacin: a broad-spectrum quinolone for superficial eye infections]. AB - Norfloxacin is a synthetic antibiotic belonging to the fluoroquinolone class. At present, an oral formulation is available and indicated for the treatment of urinary tract infections. Because of the properties of norfloxacin, a 0.3% norfloxacin ophtalmic solution may be used by ophtalmologists. The molecular target of norfloxacin is DNA gyrase that regulates DNA replication. Norfloxacin is a broad spectrum antibiotic. A flurin atome in position 6 is responsible for the broad spectrum of activity as compared with the first generation quinolones. MICs of norfloxacin against Haemophilus influenzae, Neisseria gonorrhoeae, Staphylococcus aureus, Pseudomonas aeruginosa, and enterbacteriaceae are low or intermediate. Norfloxacin is a bactericidal drug of which MBCs are equivalent to or twice as high as MICs against the majority of organisms. The proportion of norfloxacin resistant strains is limited and, at present, no plasmid resistance has been observed. This explains the activity of norfloxacin against clinical isolates whose drug resistance is plasmid-mediated. Norfloxacin resistance is chromosomic, but the mutation rate is low. There is no cross-resistance between quinolones and other classes of drug, with the exception of drug resistance related to changes in the bacterial outer membrane proteins. A low decrease in norfloxacin susceptibility is observed in case of resistance to first generation quinolones. The above-mentioned properties make norfloxacin in ophtalmic solution a first line drug for treatment of superficial ocular infections and a second line drug for treatment of infections due to organisms resistant to other drugs. PMID- 2235091 TI - Evaluation of the white blood cell differential given by the new analyser Coulter STKS in both hematological and non-hematological patient groups. AB - The White Blood Cell differential given by the new analyser Coulter STKS was studied in a group of hospitalized patients originating from non-hematological departments (group 1; n = 290) and a group of patients suffering from an hematological disease (group 2; n = 106) with blood smear abnormalities. A good relationship between the reference method and the STKS results was shown in 200 patients without hematological abnormalities. Both sensitivity and reliability of alarms were evaluated in both groups. In group 1, we noticed respectively: 208 true negative, 40 true positive, 7 false negative, 35 false positive. Six of the seven false negative results were related to the presence of a slight myelemia without hematological significance, one to the presence of small quantity of circulating blasts with a leuconeutropenia. In group 2, all abnormalities seen on the blood smear were detected by the Coulter STKS either by an alarm message (93 cases) or by an increase of the lymphocyte population (9 cases) in some chronic lymphocyte leukemias, or by an important leuconeutropenia (4 cases) in acute treated leukemias. The results of the White Blood Cell differential performed with the Coulter STKS exhibited a good relationship with the reference method for normal bloods and a good reliability for detection of abnormal cells. PMID- 2235092 TI - Follicular immunoblastic lymphoma: neoplastic counterpart of the intrafollicular immunoblast? AB - B-immunoblasts, the precursors of plasma cells, occur predominantly in the interfollicular regions of lymphoid tissue, but may also occur in small numbers in germinal centres (intrafollicular immunoblasts). We report an unusual case of de novo follicular lymphoma composed of immunoblasts with an appreciable amount of plasmacytoid cytoplasm. We postulate that follicular immunoblastic lymphoma probably represents the neoplastic counterpart of the intrafollicular immunoblast. PMID- 2235093 TI - Mycobacterium terrae tenosynovitis. AB - Atypical mycobacteria causing extra-pulmonary disease in man are well documented. These infections are manifested by the presence of ulcers, abscesses and lymphadenitis. Mycobacterium marinum is particularly noted for infections involving the synovium, tendon sheaths, bursae and bone. Of lesser note is Mycobacterium terrae (radish bacillus), a nonchromogen also associated with tenosynovitis. We are not aware of any previous report of the association of M. terrae with synovitis in Australia. This case report describes a culture-proven case of tenosynovitis caused by M. terrae. PMID- 2235094 TI - Angiosarcoma of the prostate. An immunohistochemical study of a case. AB - A rare case of angiosarcoma occurring in the prostate of a 35-year-old man and characterized by a classical histological appearance is presented. The diagnosis was confirmed by the demonstration of factor VIII-related antigen in the tumor cells. The case illustrates the aggressive nature of angiosarcoma of the prostate. PMID- 2235095 TI - Grossly elevated serum prostatic acid phosphatase in a patient with carcinoid. AB - We report a case of carcinoid, diagnosed histochemically and biochemically, which was associated with grossly elevated serum prostatic acid phosphatase and normal serum prostate specific antigen. PMID- 2235096 TI - Macromolecular lactate dehydrogenase: an innocent bystander. AB - Lactate dehydrogenase (LD) activity is often increased in malignancy, and may occasionally be a useful tumor marker. In the case reported here, a persistently increased LD activity led to an extensive search for a neoplasm. Results of routine investigations were normal, but LD electrophoresis followed by gel filtration and immunofixation confirmed the presence of a circulating macromolecular LD, comprising IgAK bound to LD. Altogether it may provoke unnecessary investigations, the LD-IgA complex currently has no diagnostic significance. PMID- 2235097 TI - Osteolytic skeletal lesions in chronic myeloid leukemia. PMID- 2235098 TI - Apolipoprotein localization in the human bile duct and gallbladder. AB - Apolipoproteins AI, AII and B were identified in the normal and pathological human bile duct and the gallbladder epithelium using an avidin-biotin immunoperoxidase technique. Small intestine and stomach sections served as positive and negative controls respectively. Staining was focal for apolipoproteins AI and AII, and continuous for apolipoprotein B. In addition to homogenous and granular cytoplasmic staining, foamy cytoplasmic staining, particularly for apolipoproteins AI and AII, was observed around lipid droplets in cells containing much lipid. No correlation between a particular pathological condition of the gallbladder (acute cholecystitis, mucocele, chronic cholecystitis, cholesterolosis) and staining pattern or intensity of staining was found for any of the apolipoproteins, although both apolipoproteins AI and AII stained more intensely than apolipoprotein B in each group. Positive staining was also found for all apolipoproteins in epithelial cells which had invaded the underlying connective tissue (gallbladder carcinoma), suggesting that the epithelial cells are capable of synthesizing apolipoproteins de novo. In this latter case, apolipoprotein B stained more intensely than for either AI or AII, and significantly (p less than 0.05) more strongly than that found in the other pathological groups. The identification of apolipoproteins in the gallbladder epithelium raises the interesting question of their origin and functional role. PMID- 2235099 TI - Human leucocyte differentiation antigens: review of the CD nomenclature. AB - In February 1989 the 4th International Workshop and Conference on Human Leucocyte Differentiation Antigens was held in Vienna. At this meeting the structure and function of recognized cellular antigens was reviewed and new antigens defined. In addition, information was obtained on the molecular genetics of antigens from gene cloning and sequencing. The CD (clusters of differentiation) nomenclature was extended, giving a total of 78 CD clusters, and some previously described CD groups revised and sub-divided. In this paper new information on the structure and function of leucocyte antigens presented at the meeting will be discussed. In addition, descriptions of the newly defined CD clusters and changes to established clusters will be outlined. PMID- 2235100 TI - Comparison of thromboplastins using the ISI and INR system. AB - Twelve thromboplastins were tested against a secondary reference thromboplastin (human brain CRM BCR No. 147) or a tertiary house standard (human brain thromboplastin) with plasmas from normal healthy individuals and patients on oral anticoagulant therapy. The relationship between the prothrombin ratios of the thromboplastins tested versus the reference reagent was either a straight or curved line. The International Sensitivity Index (ISI) was estimated for each of the test thromboplastins and these ranged from 0.98 to 2.24. Some ISIs stated by manufacturers were different from our results. Thromboplastins with a high ISI showed a loss of sensitivity in assessing the level of anticoagulation at the upper end of the therapeutic range. In addition, the 95% Confidence Interval (CI) of the ISI estimations were widest for thromboplastins with the highest ISIs. Conversion of the prothrombin ratio to International Normalized Ratio (INR) was most accurate with the Australasian Reference Thromboplastin (ART) and least accurate with reagents having an ISI of 2.00 and over. Thromboplastins with an ISI between 1.10 and 1.50 may be adequate for the control of oral anticoagulant therapy, but were less accurate than a thromboplastin with an ISI approximating 1.00. Factors other than ISI should be considered in the choice of a thromboplastin, in particular a measurement of the accuracy of the ISI estimation such as the 95% confidence interval estimation used here. PMID- 2235101 TI - Ras gene product expression in blood and marrow smears of patients with acute leukemia: importance of fixation. AB - Activation of ras protooncogenes by any of several possible mutations in codons 12, 13 or 61 has been demonstrated in a variety of human malignancies, including acute non-lymphoblastic leukemia (ANLL). In situ staining for the ras gene product, p21, has been demonstrated in carcinomas of several sites. High levels of p21 expression have been associated with histologic anaplasia in prostate cancer and regional lymph node metastasis in breast cancer. We examined 16 marrow aspirates and blood smears from patients with acute leukemia, predominantly ANLL, and eight controls. Marrow aspirates or blood were smeared on glass slides and fixed immediately in 10% buffered formalin. p21 was examined with avidin-biotin linked immunoperoxidase visualization. Particular attention must be paid to antibody selection and fixation protocol to demonstrate p21, owing to its rapid degradation ex vivo. Three of 16 patients exhibited occasional high p21 expression primarily in leukemic blasts, but in no case were more than 10% of blast cells positive. Normal reticuloendothelial and myeloid cells occasionally exhibited mild to moderately heavy staining, but megakaryocytes, erythroid precursors, lymphocytes and plasma cells were consistently negative. Most patients, 5 normal volunteers and 3 patients with non-malignant disease, exhibited no reactivity, or only a faint blush. These data suggest that while point mutation and concomitant activation of c-N-ras occurs regularly in ANLL, high levels of ras p21 expression are rarely found with this technique. PMID- 2235102 TI - Red cell folate assays: some answers to current problems with radioassay variability. AB - Red cell folate specimens were added to the Quality Assurance Program (QAP) of the Royal College of Pathologists of Australasia in 1986. The interlaboratory variation in the results of these red cell folate surveys has been persistently unsatisfactory. This study reports an investigation into the factors contributing to the wide variation of results reported in QAP surveys. Survey results were studied, replies to a questionnaire regarding methods sent to all participants were assessed and some new experimental studies were performed. Factors contributing to the poor QAP results include variation in dilution and diluent, calculation errors, failure to freeze the hemolysate prior to assay and to follow the kit manufactorer's instructions, stability of dithiothreitol, and variations in kit methods, especially in the release of bound folate by "boil" and "no-boil" methods. Photodecomposition and the form and concentration of ascorbate may also be significant. Adequate preparation of the hemolysate sample should ensure release of all protein-bound red cell folate with the reduction of all folates to a single form. Kit manufactures, users and the QAP committee can all contribute in all attempt to rectify current sources of error. PMID- 2235103 TI - Neurotic and psychosomatic disorders. Interdependence in terms of the search activity concept. AB - There are no correlations between MMPI Hysteria (Hs) and Depression (D) scales in psychosomatic patients in contrast to other patients with somatic disturbances, neurotic disturbances, and in healthy subjects. The roles of depression and hypochondria in the dynamics of psychosomatic disturbances are discussed according to the search activity concept. It is suggested that hypochondriacal complaints are prognostically favorable in comparison with anxiety-depression complaints. PMID- 2235104 TI - Pavlov, psychoanalysis, and neuroses. AB - Pavlov's discovery of experiment neurosis was serendipitous, yet it was made under the influence of Breuer and Freud's case of Anna O. In 1914, Pavlov's disciple N. R. Shenger-Krestovnikova, exploring the limits of visual discrimination in dogs, noticed that when the discrimination was difficult, the dogs' behavior became disorganized. Pavlov drew an analogy between the condition of Shenger-Krestovnikova's dogs and their disorganized behavior with Anna O.'s situation and her neurotic reaction. Pavlov concluded that he had demonstrated in the laboratory the elements of neurosis in animals and human alike. Schilder's criticism of his position, his later study of human neuroses in clinical settings, and the views of Janet may have induced Pavlov to differentiate between animal and human neuroses. PMID- 2235105 TI - Locus of semantic generalization of the galvanic skin response and possible inhibitory influence of conditional stimuli upon unconditional response following conditioning with innocuous and noxious unconditional stimuli. AB - Two different problems were investigated using the GSR index of the orienting reflex (OR): 1) the locus of semantic generalization; and 2) a possible inhibitory influence of the CS upon the UCR. Two experiments were conducted. One experiment employed an innocuous USC, and a second similar experiment used a loud noise as the UCS. Unidirectional word associates were employed in the test of the direction of semantic generalization. Constant and varying CS words were used to test the possible inhibitory influence of the CS upon the UCR. Evidence was obtained of semantic generalization occurring in the training and in the test situation. There was no evidence of the CS developing inhibition over the UCR. Theoretical interpretation of both phenomena were considered. The need for developing theories of conditioning of the OR in humans was emphasized in contrast to current efforts to apply inappropriate cognitive animals learning theories which fail to consider biologic constraints. PMID- 2235106 TI - Reaction time task as unconditional stimulus. Comparing aversive and nonaversive unconditional stimuli. AB - Nonaversive unconditional stimuli (USs) are seldom used in human classic conditioning of autonomic responses. One major objection to their use is that they produce deficits in electrodermal (ED) second- and third-interval response conditioning. However, a nonaversive reaction time (RT) task that includes feedback of success has been shown to be an effective US while avoiding this disadvantage (Lipp and Vaitl 1988). The present study compared this new RT task (RT-new) with a traditional RT task (RT-old) and with a standard aversive US (shock) in differential classic conditioning of ED, heart rate (HR), and digital pulse volume (DPV) responses. Eight-second-delay differential conditioning was applied in three groups of 12 subjects each. Simple geometric features (square, cross) displayed on a television screen served as conditional stimuli (CS+ and CS ). In acquisition, there were no statistically significant differences among the groups; differential conditioning did occur in HR, first- and second-interval ED responses, and first-interval DPV responses. Separate analyses within each group, however, revealed that there was no second-interval ED conditioning in the RT-old group. During extinction, neither DPV nor second-interval ED conditioning could be obtained, whereas HR and first-interval ED conditioning occurred in each group. In third-interval omission ED responses, RT-old and shock groups exhibited extinction, while response differentiation was maintained in the RT-new group throughout extinction. The RT task including feedback proved to be as reliable a US as a standard aversive US, whereas application of a traditional RT task again yielded some weaknesses in second-interval ED conditioning. PMID- 2235108 TI - A pediatrician's view: some things old, some things new. PMID- 2235107 TI - Kupalov's concept of shortened conditional reflexes: psychophysiological and psychopharmacological implications. PMID- 2235109 TI - Viral otitis media. PMID- 2235110 TI - Measles vaccine and measles control. PMID- 2235111 TI - Developmental regulation of angiotensinogen gene expression in sheep. AB - It has been suggested that the liver is not the main source of angiotensinogen during fetal life in rats, but that the kidney is an important site of fetal angiotensinogen synthesis. In an effort to determine if this phenomenon is specific to the rat or applicable to other species, we compared the ontogenic changes in hepatic and renal angiotensinogen mRNA expression in fetal (60, 90, 118, and 138 d of gestation, term being 145 d), newborn (7 d postnatal), and adult sheep. Total RNA was extracted, subjected to Northern blotting and hybridized using a full-length rat radiolabeled antisense RNA. Angiotensinogen mRNA sequences were detected in all fetal liver samples and appeared to increase 3-fold from 60 to 138 d gestation and then to decrease after birth. In contrast, angiotensinogen mRNA could not be detected in renal cortical tissue of 118 or 138 d fetuses, or newborn or adult sheep. We conclude that, unlike in the rat, liver angiotensinogen gene expression is detectable during the 2nd trimester of gestation in sheep and is developmentally regulated. Furthermore, in contrast to the fetal rat, angiotensinogen mRNA sequences were undetectable in fetal sheep kidney. PMID- 2235112 TI - The effect of maternal ethanol ingestion on fetal vitamin A in the rat. AB - The effect of maternal ethanol ingestion on fetal tissue vitamin A was investigated. Pregnant rats were pair-fed control diets or diets containing 36% of energy as ethanol. After 17 or 21 d gestation, fetuses were removed and fetal and maternal tissues were analyzed by HPLC for retinol and retinyl palmitate. Ethanol consumption resulted in fewer fetuses per pregnancy, increased number of resorptions, and increased numbers of gross fetal abnormalities. In maternal tissues, ethanol consumption resulted in greater lung and kidney vitamin A concentrations. In the fetuses of ethanol-consuming pregnancies, free retinol in liver was higher at d 17. However, fetal liver palmitate levels and total retinyl palmitate in liver, lung, and kidney were lower in ethanol-fed rats at d 21 of gestation. Fetal lung retinyl palmitate concentrations were greater at both d 17 and d 21, and kidney levels were also greater at d 21. In conclusion, the ingestion of ethanol by pregnant rats is associated with a reduction in fetal liver vitamin A levels and an elevation in the levels of lung and kidney vitamin A, indicating possible altered vitamin A metabolism as a result of ethanol consumption. PMID- 2235113 TI - Effect of aminophylline on diaphragmatic contractility in the piglet. AB - Minute ventilation, arterial blood gases, arterial pH, cardiac output, and transdiaphragmatic force generation, both during spontaneous ventilation and in response to phrenic nerve stimulation during airway occlusion at end expiration, were measured in nine anesthetized, tracheostomized piglets before and 30 min after parenteral infusion of 20 mg/kg aminophylline. Serum theophylline levels averaged 109 +/- 21 mumol/L (19.7 +/- 3.7 micrograms/mL) at 30 min postinfusion. No significant changes were noted in pH, blood gases, blood pressure, or ventilatory measures after aminophylline. Aminophylline infusion also had no effect on transdiaphragmatic force generation at any frequency of phrenic nerve stimulation studied. It is concluded that aminophylline has no effect on diaphragmatic contractility in the quietly breathing, nonfatigued piglet. PMID- 2235114 TI - Biotin labeling of red cells in the measurement of red cell volume in preterm infants. AB - Determination of circulating red cell volume (RCV) in anemic preterm infants is, in theory, a better indicator of transfusion needs than Hb concentration. Our study reports the results of RCV measurement using biotin labeling of red cells on 40 occasions in preterm infants of 25-34 wk gestation. In 20 infants, who had estimations made within 24 h of birth, the RCV varied between 17.7 and 66 mL/kg. Twenty measurements were made at a later age at the time of a blood transfusion. RCV values were between 13.1 and 41.5 mL/kg before transfusion. In 13 infants, RCV was determined simultaneously using two methods, biotin and dilution of autologous HbF with donor HbA at transfusion. There was no significant difference between the results of RCV estimations using these two methods. Our study demonstrates that biotin labeling is an effective method for determining RCV in preterm infants. PMID- 2235115 TI - Placental transfer of glucose and amino acids in intrauterine growth retardation: studies with substrate analogs in the awake guinea pig. AB - After experimentally inducing growth retardation by unilateral uterine artery ligation in midpregnancy, placental blood flow (PBF) (microsphere technique) and placental transfer of 14C-aminoisobutyric acid (AIB) and 3H-methylglucose (MG) were studied at d 44, 50, or 63 of gestation in 19 chronically catheterized awake guinea pigs. At d 44, fetal wt (FW) and placental wt were reduced by 16 and 18%, respectively, in the ligated horn and FW/PBF was increased by 122%. Placental efficiency to transfer MG and AIB (fetal dpm/g placenta) was maintained in the ligated horn, feto-placental extraction (feto-placental dpm/PBF) was increased, and placental transfer of the substrate analogs (fetal dpm/g fetus) was unchanged. At d 50 and 63, placental wt and FW were reduced in proportion (approximately 40%) in the growth-retarded group and FW/PBF was increased by 80 and 51%, respectively. Placental transfer of AIB was reduced by 33% at d 50 and by 18% at d 63. In addition, placental efficiency to transfer AIB was reduced by 36% at d 50 and by 22% at d 63 in the growth-retarded group. Fetal uptake of MG per g fetus was slightly reduced (-6%) at d 50 of gestation, but unaffected at d 63. Extraction of MG from the maternal PBF was increased, whereas the wt-specific transfer capacity of the placenta was unaltered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235116 TI - Comparison of urinary growth hormone and IGF-I excretion in small- and appropriate-for-gestational-age infants and healthy children. AB - The output of urinary growth hormone (GH) and IGF-I were quantitated by RIA in 12 h urine collections obtained from infants who were preterm, small for gestational age (PT-SGA, n = 13); preterm, appropriate for gestational age (PT-AGA, n = 27); full term, small for gestational age (FT-SGA, n = 13); and full term, appropriate for gestational age (FT-AGA, n = 29); and from normal children (n = 33). The amounts of GH and IGF-I (mean +/- SEM) excreted by the PT-SGA and FT-SGA infants were not significantly lower than those excreted by the PT-AGA and FT-AGA groups, respectively [GH (micrograms/kg): PT-SGA 13.7 +/- 3.1 versus PT-AGA 14.0 +/- 2.2, FT-SGA 7.8 +/- 2.4 versus FT-AGA 6.6 +/- 1.8; IGF-I (nmol/kg): PT-SGA 0.52 +/- 0.09 versus PT-AGA 0.53 +/- 0.04, FT-SGA 0.31 +/- 0.05 versus FT-AGA 0.35 +/- 0.04]. All infant groups exhibited significantly greater outputs of urinary GH and IGF-I compared with the children (p less than 0.01). The plasma concentrations of GH in all infant groups were high, whereas the plasma IGF-I levels were low. Microalbumin and beta-2 microglobulin excretion did not correlate with urinary GH and IGF-I output. Despite the higher microalbumin output in FT babies, urinary GH and IGF-I excretion was lower in these groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235118 TI - Reversal of venous blood flow with atrial tachycardia and hydrops in fetal sheep. AB - The purpose of this project was to characterize the reversal of blood flow in the proximal inferior vena cava (IVC) seen in fetal sheep with pacing-induced atrial tachycardia and hydrops. We successfully operated on seven pregnant ewes at 118 130 d gestation to attach ECG and pacing wires, insert vascular catheters, and place Doppler flow probes around the common aortic trunk and the IVC. We also performed two-dimensional and Doppler ultrasonographic exams at baseline, after initiation of pacing, and daily thereafter. All fetuses developed hydrops. Ultrasonographic appearance of ascites and pleural effusion occurred within 4 h in four fetuses and within 48 h in all fetuses. Atrial pacing did not affect arterial pH or arterial O2 tension, but arterial CO2 tension increased by a small amount. Mean IVC pressure increased 75%, whereas mean aortic pressure remained the same. Concentrations of plasma protein and albumin and the hematocrit did not change with atrial pacing. Doppler ultrasound examination and Doppler IVC flow tracings showed that flow reversal began immediately with atrial pacing and disappeared immediately with cessation of pacing. Reversed flow was 21% of forward flow. Inspection of simultaneous recordings of ECG, Doppler aortic and IVC flows, and aortic and IVC pressure tracings revealed that the reversed blood flow occurred in diastole in conjunction with atrial contraction and, therefore, could not be due to tricuspid insufficiency. Our findings of increased venous pressure and reversed venous blood flow suggest that ventricular function is impaired and further suggest that oxygen supply to the ventricles may not be sufficient for the increased demand. PMID- 2235117 TI - Effect of sleep on regional blood flow distribution in piglets. AB - The regional distribution of blood flow to the brain and to other major organs was studied during wakefulness and sleep in growing piglets. A young group was studied at 6.8 +/- 1.3 d of age and an older group at 33.5 +/- 5.5 d. Two d before the experiments, we instrumented the animals for measurement of blood flow by the microsphere technique. We determined sleep state using EEG and behavioral criteria. Although we did not find significant differences in blood gas tensions and cardiac output with changes in behavioral states, we did note a number of important changes in brain and muscle blood flow with sleep. 1) Although total brain blood flow changed little between wakefulness and sleep at both ages, regional differences existed. Indeed, at both ages, during rapid eye movement sleep (active sleep), blood flow to the thalamus-hypothalamus and brainstem was significantly higher than during wakefulness (p less than 0.025); in older piglets, blood flow to these two regions was significantly lower in quiet sleep than in wakefulness (p less than 0.05). 2) Blood flow to most skeletal muscle groups, and particularly to the diaphragm, was lower during sleep than during wakefulness. 3) Age did not have a significant effect on the regional distribution of blood flow during sleep. We conclude that behavioral states influence the regional distribution of blood flow in early life, but not in an age-dependent fashion. We speculate that, because no difference was observed in other hemodynamic variables, the regional changes in organ blood flow with sleep most probably reflect the differences in local metabolic needs. PMID- 2235119 TI - Early changes in the permeability of the blood-brain barrier produced by toxins associated with liver failure. AB - Our study was designed to determine whether substances that appear in the serum during the course of liver failure have a detrimental effect on the passive permeability of the blood-brain [blood-cerebrospinal fluid (CSF)] barrier. Lactic acid, octanoic acid, and ammonia were infused into rabbits for 4 h. The permeability changes of the blood-brain barrier were quantified by infusing polyethylene glycol 400 (PEG 400) and measuring the quantity and average mol wt of the PEG 400 that entered the CSF. The lipid solubility and effective diffusional radius of the PEG molecules were also quantified to provide greater precision for measurements using this probe. None of the animals receiving toxic infusions became seriously ill during the infusions. Low dose infusions of lactic acid, octanoic acid, and ammonia increased the effective pore diameter of the blood-brain barrier from 7.3 A to an average of 8.5 A. The amount of PEG entering the CSF increased from 1.7 to 4.0 (p less than 0.025), 4.7 (p less than 0.025), and 6.7 (p less than 0.001) mmol/L, respectively. Rabbits with galactosamine induced liver failure had 10.1 mmol/L PEG 400 in the CSF (P less than 0.001) before any evidence of cerebral edema. These changes occur soon after these toxins accumulate in the plasma and may alone or together with other toxins account for the permeability changes that allow neurotoxic substances to enter the brain during hepatic disease and encephalopathies such as Reye's syndrome. PMID- 2235120 TI - Effect of gentamicin on the auditory brainstem evoked response in term infants: a preliminary report. AB - Seven essentially healthy term infants who received gentamicin starting on the 1st day of life for prolonged rupture of membranes and maternal fever were compared with nine healthy term infants to determine whether this drug induces alterations in the auditory pathway. The auditory pathway was studied on the 3rd day of life by analyzing brainstem auditory evoked potentials elicited by a click stimulus presented at the infant's ears. Latencies of components III and V, interval I-III, and interval I-V were significantly prolonged in the gentamicin group, indicating impairment of the central component of the auditory pathway. Peak and trough serum gentamicin levels all fell within the recommended therapeutic range. The study indicates that short course gentamicin therapy in healthy newborn infants can lead to abnormality of auditory function. PMID- 2235121 TI - Protein metabolism in phenylketonuria and Lesch-Nyhan syndrome. AB - Animal and in vitro studies have implicated decreased protein synthesis in the pathogenesis of tissue damage in phenylketonuria (PKU) and of growth failure in Lesch-Nyhan syndrome. Protein turnover was measured in vivo in ten young adult subjects with classical PKU, two subjects with hyperphenylalaninemia, and three children with Lesch-Nyhan syndrome using techniques based on continuous infusions of [13C]leucine and, in Lesch-Nyhan subjects, [2H5]phenylalanine. The PKU subjects had various degrees of dietary phenylalanine restriction and plasma phenylalanine levels at the time of study ranged from 450-1540 mumol/L (mean 1106). Plasma phenylalanine in the two hyperphenylalaninemic subjects was 533 and 402 mumol/L. Rates of protein synthesis in all PKU subjects (mean 3.71 g/kg/24 h, range 2.68-5.10, [13C]leucine as tracer) were in a range similar to or above control values (mean 2.97, range 2.78-3.22, n = 6), as were rates of protein catabolism (PKU mean 4.23 g/kg/24 h, range 3.15-5.45; controls 3.64, 3.50-3.91). Protein turnover values in hyperphenylalaninemia were also similar to those in controls. With [13C]leucine as tracer, both mean protein synthesis and catabolism values in Lesch-Nyhan subjects (mean 4.80 and 5.64 g/kg/24 h, respectively) were higher than values in control children matched for protein intake (synthesis 4.32 +/- 0.74 (SD) and catabolism 4.85 +/- 0.57 (g/kg/24 h, n = 5). Similar results were obtained in Lesch-Nyhan subjects using [2H5]phenylalanine as tracer. These results suggest that protein turnover is not decreased in either PKU or Lesch Nyhan syndrome. This conclusion is inconsistent with the hypothesis that tissue damage in PKU results from impaired protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235122 TI - Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy. AB - Evidence is emerging that primary systemic carnitine deficiency, a potentially lethal but eminently treatable inborn error of fatty acid oxidation, involves a cellular defect in the uptake of carnitine. We present four unrelated children with primary carnitine-responsive cardiomyopathy, weakness (with or without hypoketotic hypoglycemic encephalopathy), low serum and/or tissue carnitine concentrations, and severe renal carnitine leak. Dicarboxylic acids were absent in the urine of three children who were tested, and all four had a rapid and dramatic improvement in cardiac function, strength, and somatic growth after carnitine therapy. We studied carnitine uptake in cultured skin fibroblasts from all four children and seven of the eight healthy nonconsanguinous parents. [3H]L carnitine uptake was evaluated in vitro under linear time kinetics. Substrate concentrations were varied from 0.1 to 1000 microM. Physiologic uptake was determined at carnitine concentrations between 0.1 and 50 microM. Nonspecific uptake was determined at a concentration of 10 mM. The four patients had negligible uptake throughout the physiologic range, implying a marked deficiency in the specific high-affinity, low-concentration, carrier-mediated uptake mechanism. At a concentration of 5 mumol/L, the mean velocity of uptake in the four patients was 2% of control values. Their parents showed intermediate maximal rates of carnitine uptake ranging from 13 to 44% of control Vmax values, but normal Km values, suggesting that the heterozygotes had a reduced number of normal functioning carnitine transporters. The observed reduction in Vmax values for the parents supports an autosomal recessive inheritance pattern and may be a more sensitive indicator of heterozygosity than serum carnitine concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235124 TI - Development of ornithine metabolism in the mouse intestine. AB - Circulating arginine available for synthesis of protein is produced in the kidney of the adult mammal by the action of the last two enzymes of the urea cycle, argininosuccinate synthase and argininosuccinate lyase. In a previous publication, we reported the presence of a complete biosynthetic pathway for arginine in the intestine of the neonatal mouse at a time when no other endogenous sources of arginine were available. Our present study was aimed at the determination of the source of ornithine used by the intestine of the neonatal mouse for the synthesis of arginine. We established the developmental profile of the two intestinal mitochondrial enzymes, pyrroline 5-carboxylate synthase and ornithine aminotransferase, responsible for the conversion of glutamate to ornithine. Both enzymatic activities were found to be significantly elevated throughout the suckling period with a peak of activity during the 2nd wk of life. Glutamate dehydrogenase activity in the intestine did not appear to be developmentally regulated during the suckling and weaning periods; therefore, this enzyme was used as a convenient marker to quantify mitochondrial preparations. Ornithine decarboxylase activity was undetectable in the intestine of the mouse during the suckling period and was detected briefly at weaning, indicating that ornithine synthesized in the intestinal mitochondria is probably not diverted actively into the polyamine pathway and is available for synthesis of arginine by the enzymes of the urea cycle. PMID- 2235123 TI - Failure of L-carnitine to protect mice against hyperammonemia induced by ammonium acetate or urease injection. AB - Reports indicate that L-carnitine administration before 100% lethal dose of ammonium acetate suppresses the symptoms of ammonia toxicity and prevents death in mice. However, we have been unable to confirm this observation. The cause of discrepancy between our results and the results of others was investigated with two models of hyperammonemia in mice: 1) that induced by intraperitoneal injection of urease and 2) that induced by intraperitoneal injection of ammonium acetate. L-Carnitine administration failed to protect mice against ammonia toxicity induced by intraperitoneal injection of urease. Mortality in mice treated with L-carnitine 30 min before injection of ammonium acetate was similar to that of controls pretreated with saline. Ammonia and urea levels in plasma, liver, and brain were also similar in both groups. However, the values were significantly lower than those in mice denied either pretreatment before the ammonium acetate challenge. These results indicate that pretreatment acts to reduce blood and tissue ammonia simply by diminishing the rate of absorption of the challenge, owing to the dilution of ammonium acetate upon mixing with the contents of the peritoneal cavity. Thus, any protocol that does not compare results of a putative protective agent with those obtained with an equal volume of solvents or saline runs the risk of ascribing protective property to the agent when the protection may, in fact, have been afforded by the solvent. PMID- 2235125 TI - Transport of biotin in the ileum of suckling rats: characteristics and ontogeny. AB - Unlike adult rats, which transport biotin preferentially in the jejunum of the small intestine, suckling rats transport biotin preferentially in the ileum. The characteristics and kinetics of the transport process of biotin in the ileum of developing suckling rats and the subsequent maturation of the process in weanling and adult rats are not known and, therefore, are examined in this study. Transport studies were performed in suckling (16-d-old), weanling (25- to 27-d old), and adult (90-d-old) rats using the everted sac technique. Transport of biotin in the ileum of suckling rats was significantly higher (p less than 0.01) than that in weanling rats, and transport in weanling rats was in turn significantly higher (p less than 0.01) than that in adult rats. In all age groups examined, transport of biotin was found to be Na(+)-dependent and saturable as a function of concentration within the physiologic range (less than 10 microM), but linear at high concentrations. However, the Vmax of the carrier mediated transport system of biotin showed progressive decrease with maturation (3290 +/- 363, 829 +/- 47, and 463 +/- 19 pmol/g tissue wet wt/15 min in suckling, weanling, and adult rats, respectively), whereas no significant changes were observed in the apparent Km (2.8 +/- 0.6, 2.6 +/- 0.4, and 3.4 +/- 0.4 microM in suckling, weanling, and adult rats, respectively). These findings suggest that maturation is associated with a decrease in the number (and/or activity) but not the affinity of the ileal biotin transport carriers. Transport of biotin by the diffusion process was also found to decrease with maturation (diffusion rates of 144, 86.5, and 40 pmol/g tissue wt/15 min were found for suckling, weanling, and adult rats, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235126 TI - Mechanism of the unique susceptibility of deep cortical glomeruli of maturing kidneys to severe focal glomerular sclerosis. AB - The alterations in single glomerular hemodynamics, glomerular size, and development of glomerular sclerosis after subtotal nephrectomy were assessed in approximately 32-d-old young and greater than 3-mo-old adult Munich-Wistar rats. In 6 wk, young rats developed more pronounced glomerular sclerosis and more marked elevation in blood urea nitrogen. The deep (versus superficial) cortical region of young rats was characterized by having a greater number of glomeruli with advanced sclerosis. Single nephron glomerular filtration rate of superficial glomeruli of the young increased to a much greater extent than whole kidney glomerular filtration rate, whereas there were comparable post-subtotal nephrectomy increases in whole kidney glomerular filtration rate in these two age groups, indicating that the deep glomeruli were exposed to a lesser hemodynamic load than were the superficial. Since the remnant nephrons of young and adult rats achieved equally high glomerular pressures and comparably large glomerular size shortly after subtotal nephrectomy, the unique susceptibility of young glomeruli to sclerosis is attributed to the intrinsic property of these glomeruli, rather than the abnormal hemodynamics or stimuli promoting hypertrophy and mesangial matrix accumulation imposed upon the glomeruli. PMID- 2235127 TI - Society for Pediatric Research presidential address 1990: pediatric research- integrated evaluations to achieve insights into organ function. PMID- 2235128 TI - In vivo effect of interleukin-6 on cycling status of hematopoietic progenitors from adults and neonates. AB - In vitro, IL-6 can induce hematopoietic progenitors to progress from G0 into cycle, but a role for IL-6 in regulating cycling status of progenitors in vivo has not been established. In our studies, groups of five to six adult and newborn rats received i.v. injections of either IL-6 (1 ng/g body wt) or the vehicle (control), after which cycling of hematopoietic progenitors was evaluated by tritiated thymidine suicide. Progenitors from adult rats injected with the control had thymidine suicide rates of 7 +/- 1% (mean +/- SEM), compared with 23 +/- 7% in the IL-6 recipients (p less than 0.02). Progenitors from newborn rats injected with the control had thymidine suicide rates of 19 +/- 2%, compared with 29 +/- 1% in the IL-6 recipients (p less than 0.003). In addition, IL-6 administration resulted in release of cells from the neutrophil storage pool into the circulation, as evidenced by fewer polymorphonuclear cells flushed from the long bones (neonates, p less than 0.001; adults, p less than 0.003), a rise in blood neutrophil concentration (neonates, p less than 0.001; adults, p less than 0.05), and a leukocyte "left shift" (neonates, p less than 0.001; adults, p less than 0.01). Thus, the effects of IL-6 in vivo in newborn and adult rats include cycle induction of hematopoietic progenitors and release of neutrophils from the storage pool into the circulation. PMID- 2235129 TI - Discrimination between low dietary zinc and endotoxin exposure: a model study on weaning rats. AB - To establish a parameter for zinc status that is independent of the occurrence of infection, we studied the effects of low dietary zinc and endotoxin in weaning rats 21 d after 65Zn intubation. We monitored aspects of zinc status (tissue zinc content, 65Zn distribution, and specific 65Zn activity in tissue) and 65Zn metabolism (absorption, excretion, and biologic half-life), as well as weight gain, feed conversion, and dietary zinc use. The low zinc diet induced classical deficiency with losses of bone zinc, resulting in lower content (7.4 versus 19.6 mumol) and higher spec act (17 versus 8 kBq/mumol). Other tissue-specific and plasma-specific activities were also higher (overall, 20 versus 8 kBq/mumol; plasma, 8 versus 4 kBq/mumol). Endotoxin caused lower total-plasma zinc (0.04 versus 0.05 mumol) but did not affect spec act (4 kBq/mumol); combined endotoxin and low-zinc diet caused low total-plasma zinc (0.01 mumol) and high spec act, as did the low-zinc diet alone (12 kBq/mumol). We conclude that plasma-spec act (or stable isotope enrichment) can serve as an index for nutritional zinc status during recurrent infection. PMID- 2235130 TI - Response to calcium of skinned gallbladder smooth muscle from newborn and adult guinea pigs. AB - Guinea pig gallbladder smooth muscle contractility undergoes a period of postnatal maturation. Because tissues from adult animals contract more forcefully than tissues from newborn animals when stimulated with agonists that activate the contractile process through different mechanisms (receptor activation, membrane depolarization), we proposed that factors unrelated to the mechanism of action of the agonist may contribute to the difference in force development between the age groups. Our study tested this hypothesis by examining the in vitro contractile response to calcium of membrane skinned muscle preparations from newborn and adult guinea pigs. Cell membranes were permeabilized using a Triton X-100 (0.5%) skinning solution. The muscle strips were rinsed in relaxing solution then contracted with calcium. The contracting solution contained either 1, 5, 10, or 20 microM calcium. Each muscle strip was stimulated with a single concentration of calcium. The results can be summarized as follows: 1) the maximal response of the skinned preparations did not differ from that of membrane intact preparations; 2) tissues from each age group contracted in a dose-response manner with the maximal response occurring at 10 microM calcium; and 3) at each calcium concentration, tissues from adult animals developed more active force than tissues from newborn animals. The data suggest that the postnatal maturation of gallbladder smooth muscle contractility includes factors involved in calcium activation of the excitation-contraction coupling process. PMID- 2235131 TI - Bile secretion of trace elements in rats with a congenital defect in hepatobiliary transport of glutathione. AB - Bile secretion of trace elements, analyzed by proton-induced x-ray emission, was studied in rats with a congenital defect in hepatobiliary transport of organic anions [Groningen Yellow (GY) rats], in which the process of bile secretion resembles that of the neonatal period. Bile flow (-41%) and biliary glutathione secretion (-99%) were drastically impaired in GY rats compared with controls. Plasma concentrations of all detectable trace elements (Fe, Cu, Zn, Mo, Br, and Se), as well as that of simultaneously determined Ca, were similar in GY and age matched control Wistar rats. Bile concentrations of Fe, Mo, Br, and Ca were also similar in both groups, resulting in a approximately 40% reduction of their secretion rates in GY rats. The concentrations of Zn (-62%) and Mn (-64%) were significantly lower in GY rats in contrast to that of Cu, which was 50% higher. Se could not be detected in bile of either group. Recovery in bile (% dose/3 h) after i.v. injection of MnCl2, CuSO4, or SeO2 (1 mg metal/kg) was lower in GY rats than in controls: Mn, 26 and 35%; Cu, 2.6 and 5%; and Se, 1.5 and 5%, respectively. Injection of ZnSO4 did not lead to increased Zn secretion in GY rats, and only 1.1% of the dose was recovered in controls. Thus, the hepatic handling of different endogenous and exogenously administered trace metals is affected to a variable extent in the GY rat. For a number of metals (e.g. Fe, Mo), this may be related to the reduced bile flow; for others (e.g. Zn, Mn, Cu), other regulatory factors appear to be responsible. PMID- 2235132 TI - Rat heart perfusion as model system for enzyme replacement therapy in glycogenosis type II. AB - Cardiac failure and skeletal muscle weakness are the main clinical features of glycogenosis type II, a lysosomal storage disorder caused by acid alpha glucosidase deficiency. In our study, we have investigated in a rat heart perfusion-recirculation system whether acid alpha-glucosidase can be taken up from the vascular system into cardiomyocytes. When rat hearts were perfused with mannose 6-phosphate-containing acid alpha-glucosidase purified from bovine testis, a 3- to 4-fold increase of enzyme activity was obtained. Perfusion with human placental acid alpha-glucosidase not containing the mannose 6-phosphate recognition marker did not have such an effect. The presence of bovine testis acid alpha-glucosidase in heart tissue was demonstrated by immunoblotting. Immunocytochemistry provides evidence for uptake of the exogenous enzyme in lysosomes of the cardiomyocytes. The relevance of these findings for enzyme therapy in glycogenosis type II is discussed. PMID- 2235133 TI - Interstitial transudate purines in normoxic and hypoxic immature and mature rabbit hearts. AB - Interstitial transudate and coronary venous concentrations of adenosine, inosine, and hypoxanthine were determined in isolated isovolumic immature and mature rabbit hearts during normoxia and hypoxia. During normoxia, interstitial transudate adenosine was lower in immature hearts compared with mature hearts. Interstitial transudate concentrations of adenosine, inosine, and hypoxanthine were 130 +/- 16 nM, 699 +/- 88 nM, and 392 +/- 80 nM, respectively, in immature rabbit hearts and 228 +/- 35 nM, 1154 +/- 126 nM, and 287 +/- 30 nM, respectively, in mature rabbit hearts. Interstitial transudate adenosine was significantly lower in the immature hearts. Coronary venous purine concentrations were 6- and 8-fold lower than their respective interstitial transudate concentrations during normoxia in both age groups. Hypoxia significantly increased interstitial transudate purines in both age groups. Interstitial transudate adenosine, inosine, and hypoxanthine increased to 1180 +/- 231 nM, 4049 +/- 500 nM, and 1099 +/- 98 nM, respectively, in immature hearts and to 1225 +/- 300 nM, 5220 +/- 1217 nM, and 876 +/- 147 nM, respectively, in mature hearts. The age-related difference in transudate adenosine levels present during normoxia was not detected during hypoxia. Venous purine levels increased during hypoxia and the gradient from interstitial transudate fluid to venous effluent was abolished for adenosine in both groups. In immature hearts, hypoxia led to higher venous effluent adenosine levels than in the mature hearts. Coronary resistance correlated with interstitial transudate adenosine in both groups, although immature hearts displayed lower resistances at all adenosine levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235134 TI - Regional cerebral blood flow after hemorrhagic hypotension in the preterm, near term, and newborn lamb. AB - Developmental changes in regional cerebral blood flow (CBF) responses to hemorrhagic hypotension during normoxia and normocapnia were determined using radioactively labeled microspheres to measure flow to the cortex, brainstem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs: 90- to 100-d preterm fetal lambs (n = 9); 125- to 136-d near-term fetal lambs (n = 9); and newborn lambs 5- to 35-d-old (n = 8). Heart rate, central venous pressure, and arterial blood pressure were monitored continuously and arterial blood gas tensions, pH, Hb, and oxygen saturation together with regional CBF were measured periodically. Hemorrhagic hypotension produced a mean decrease in arterial blood pressure of 27 +/- 4, 23 +/- 2, and 41 +/- 4% in the three groups, respectively, whereas reinfusion of the lamb's blood resulted in a return to control blood pressure within 3% in all three groups. In the pre-term fetal lamb, CBF decreased significantly in all regions during hypotension. In the near-term fetal lamb, only blood flow to the cortex decreased significantly during hypotension. In the newborn lamb, only the choroid plexus demonstrated a significant decrease in blood flow during hypotension. The lower limit of regional CBF autoregulation was identical to the resting mean arterial pressure in fetal life but significantly lower in newborn lambs. These experiments demonstrate for the first time that vulnerability to hypotension decreases with increasing maturity and that the brainstem, the phylogenetically oldest region of the brain, is the least vulnerable to the effects of hypotension at any age in the lamb model. PMID- 2235135 TI - Proximal, tracheal, and alveolar pressures during high-frequency oscillatory ventilation in a normal rabbit model. AB - To study the effect of different high-frequency oscillatory ventilation parameters on airway pressure, we measured oscillatory pressure amplitude ([Paw[) and mean airway pressure (Paw) at three sites in open-chested normal rabbits: proximal, trachea, and alveolus. Five animals were studied to test a new pleural capsule design, which was then used in two groups of animals to measure right upper (n = 4) or middle (n = 5) lobe alveolar pressures. Animals were randomly sequenced through combinations of frequency (10, 15, and 20 Hz) and fractional inspiratory time (Ti) (0.3 and 0.5) while normoxic and eucapnic. During capsule testing, we noted that alveolar pressures increased (p less than 0.05) with increasing capsule mass, suggesting that compressive forces from the capsule may alter the capsule measurement. We thus used a low-mass (430 mg) transducer system in the rabbit high-frequency oscillatory ventilation experiments. Using multifactorial analysis of variance, we found significant main effects of Ti on Paw, and of measurement site on both [Paw[ and Paw (all p less than 0.009). Frequency did not influence variations in either [Paw[ or Paw. For both Ti settings, alveolar upper lobe Paw was lower compared with that of the middle lobe (p less than 0.0005). Lengthening Ti (0.3 to 0.5) increased tracheal Paw in each capsule group (p less than 0.0005). At Ti = 0.5, tracheal Paw exceeded Paw measured proximally (p less than 0.05). Our data support in vivo alveolar Paw inhomogeneity and demonstrate significant changes in pressures within the lung related to Ti during high-frequency oscillatory ventilation. PMID- 2235136 TI - Influence of carotid denervation on the arousal and cardiopulmonary responses to upper airway obstruction in lambs. AB - Experiments were done on five lambs to determine if carotid denervation influences the arousal and cardiopulmonary responses to upper airway obstruction during sleep. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial Hb oxygen saturation. A tracheotomy was done and a fenestrated tracheotomy tube placed in the trachea. During the study, a 5 F balloon-tipped catheter was inserted into the tracheotomy tube so that air flow could be obstructed by inflating the balloon. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing room air and during experimental periods of upper airway obstruction. Carotid denervation significantly affected the arousal response to upper airway obstruction. Arousal occurred during 14 of 14 epochs in quiet sleep and during 12 of 13 epochs in active sleep before the arterial Hb oxygen saturation decreased to 30%. However, the time to arousal was increased and the arterial Hb oxygen saturation at arousal was decreased in carotid-denervated lambs compared with what we have previously observed in carotid-intact lambs. These data provide evidence that the carotid chemoreceptors and/or carotid baroreceptors play a major role in causing arousal from sleep during upper airway obstruction in lambs. Our results may have implications for sudden infant death syndrome, because it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death. PMID- 2235137 TI - Developmental changes of tropoelastin synthesis by rat pulmonary fibroblasts and effects of dexamethasone. AB - Lung elastin is an important extracellular structural protein and it has been postulated that it plays a regulatory role in alveolar formation. To study the developmental regulation of elastin gene expression, we examined the tropoelastin (TE) production in primary culture of rat pulmonary fibroblasts (RPF). We found that developmental changes in elastin production as assessed by TE synthesis and 3.6-kb TE mRNA levels were similar for RPF and whole tissue except those results from late gestation animals, with peak elastin expression occurring 7 d postnatally with a decline out to 21 d. At late gestation (20 d), TE mRNA was barely detectable in RPF but clearly detectable TE mRNA in the whole tissue, indicating that there are elastogenic cells other than RPF in the tissue at this age. When TE-producing cells were treated with dexamethasone, there was a dose dependent stimulation of TE synthesis with the maximum response at 10(-9) to 10( 7) M. Interestingly, dexamethasone had no stimulatory effect on cells from late gestation animals. The developmental window of elastin synthesis in this RPF model between late gestation and 21 d postnatal seems to correlate with the reported period of secondary alveolar formation, and thus we speculate that RPF elastogenic activity reflects that of the alveolar wall. PMID- 2235138 TI - Changes in placental blood flow in the normal human fetus with gestational age. AB - We assessed fetoplacental blood volume flow and placental resistance prospectively with Doppler sonography in 74 normal human fetuses of 19 to 42 wk gestation to determine the changes in placental perfusion with gestational age. Placental blood volume flow was assessed from the umbilical vein as the product of the mean flow velocity integral and the cross-sectional area of the umbilical vein. Placental resistance was assessed as the ratio of maximum systolic and minimum diastolic blood flow velocities from an umbilical artery. Umbilical vein blood volume flow increased exponentially (r = 0.86) with gestational age from 19 wk to term, and did not decrease in postdate fetuses. Umbilical vein blood volume flow increased linearly with fetal weight (r = 0.77), although volume flow per unit body weight changed little with gestational age. Umbilical artery velocity ratio decreased progressively, indicating diminishing placental resistance with gestational age, but did not correlate closely with umbilical vein blood volume flow. We submit that fetoplacental blood volume flow can be readily calculated directly from the umbilical vein with Doppler ultrasound and may provide a better index of placental perfusion than the umbilical artery velocity ratio. PMID- 2235139 TI - Whole body nitrogen kinetics and their relationship to growth in short children treated with recombinant human growth hormone. AB - We studied the effects of growth hormone on retention of 15N-labeled amino acids in 34 short, prepubertal, growth hormone-sufficient children and three growth hormone-deficient subjects. All 34 non-growth hormone-deficient children had apparently normal circulating growth hormone molecules and no mutations were detected in the growth hormone or IGF-I genes of any subjects. Fibroblasts from 34 children responded normally when challenged with recombinant human IGF-I. During the last 72 h of a 4-d challenge with recombinant human growth hormone (16 micrograms/kg body wt), retention of a mixed 15N-amino acid dose varied between 5.7 and 50.5%. Whole body protein synthesis, breakdown, and net anabolism calculated from the 15N kinetics were all increased by the acute growth hormone challenge. However, no routine clinical feature or laboratory determination correlated with the nitrogen retention response. After subsequent treatment (75 micrograms/kg three times a week) with recombinant human growth hormone for 1 y, there was a significant increase in height velocity, but this increase was not related significantly to pretreatment variables other than inversely to pretreatment height velocity. There was a significant (p = 0.03) correlation between the change in height velocity Z score and the degree of nitrogen retention to acute challenge with growth hormone, but this correlation was too weak (r = 0.37) to be of practical value in predicting the treatment growth response in an individual child. PMID- 2235141 TI - Treatment considerations for children with human immunodeficiency virus infection. PMID- 2235140 TI - Howland award presentation to Julius B. Richmond. PMID- 2235142 TI - Serologic evidence of subclinical pertussis in immunized children. AB - Incidental to a vaccine study involving 783 immunized children conducted at two study sites, inner city children had significantly higher geometric mean pertussis agglutinin titers compared with suburban children just before the fourth dose of diphtheria-tetanus-whole cell pertussis vaccine (47 vs. 25; P less than 0.001). Higher titers in the inner city were correlated with residence in census tracts where cases of pertussis were reported. Three hundred thirty-two children in a placebo arm of the study who were clinically observed and had paired serum samples taken during a 2- to 4-month period were analyzed for evidence of natural Bordetella infection. Twelve (11%) inner city children and three (1.3%) suburban children had spontaneous 4-fold or greater rises in at least two different pertussis antibodies measured (agglutinin, antitoxin or enzyme-linked immunosorbent assay for IgG to pertussis toxin, IgG and IgA to filamentous hemagglutinin). Eighty percent of these children had IgA to filamentous hemagglutinin. Nine of 12 inner city children with serologic evidence of pertussis lived within 6 blocks of a case of pertussis reported within 1 month of the observed antibody rise in study subjects; none had a household member with pertussis and none had symptomatic disease. PMID- 2235143 TI - Current epidemiology of pertussis in Japan. AB - Since the introduction of whole cell pertussis vaccine into general use as part of the routine immunization in 1947 under the Preventive Immunization Law, a steady decrease in reported cases of pertussis was noted until 1974. At that time the number of reported cases reached an all time low and no deaths caused by pertussis were reported. The vaccine (diphtheria-tetanus-whole cell pertussis vaccine) had been given to infants 12 weeks old or older in a 0.5-ml dose by deep subcutaneous injection; three doses were given at intervals of 3 to 8 weeks and the fourth dose (booster) was given 12 to 18 months after the third dose. The immunization was completed with those four doses. Because whole cell vaccine appeared to be associated with severe neurologic illnesses, it was temporarily suspended in 1975. The vaccine was resumed soon thereafter but the age of administration was raised to 24 to 48 months. Under these circumstances acceptance rates of pertussis occurred, reaching a peak in 1979. Although whole cell vaccine was used even after temporary suspension, it was considered to be unacceptable by the public. As a result the acellular pertussis vaccine was developed and has totally replaced whole cell vaccine since 1981. A steady decrease in reported cases of pertussis as well as the number of deaths has been noted since 1979 in accordance with increase in vaccine acceptance rates. The national surveillance system begun in 1981 demonstrated also a steady decrease in the incidence of pertussis during the past 9 years. PMID- 2235144 TI - Nosocomial bacteremias in measles. AB - The purpose of this study was to determine whether nosocomial bacteremias occurred more frequently in patients admitted with severe measles compared with general pediatric admissions. In a retrospective survey of 977 blood culture reports during a 4-year period, 1985 to 1988, the incidence of nosocomial bacteremias in patients with measles was found to be on the average of 3.37/100 admissions/year, approximately 6 times that of general pediatric patients (0.57). Gram-negative organisms (predominantly Klebsiella and Salmonella species) accounted for 86.5% of all isolates from measles patients, with 23% of these being multiply antibiotic-resistant. All the isolates from the general patients were fully susceptible to antibiotics. The duration of hospitalization was more than doubled in both groups of affected patients. The onset of hospital-acquired bacteremias occurred on an average of 11.2 days after admission in the patients with measles and 20.5 days in the general patients. Our findings revealed that nosocomial bacteremias occurred with greater frequency in patients with measles and contributed to the morbidity of these patients. PMID- 2235145 TI - Thrombocytosis after pneumonia with empyema and other bacterial infections in children. AB - Thrombocytosis is seen in association with many conditions, including infectious diseases. We studied thrombocytosis after severe bacterial infections, particularly pneumonia with empyema in children. A systematic survey of the phenomenon was conducted. Twenty-seven children admitted for pneumonia with empyema were studied. Thrombocytosis (platelet counts greater than 500 x 10(3)/microliters) was present in 92.5%. Platelet counts reached their maximum at 15.1 +/- 3.7 days (range, 7 to 25) and declined to normal after 3 weeks of illness. Compared with a healthy control group, significant thrombocytosis, but of lower incidence, was also noted in children with lobar pneumonia without pleural effusion, bacterial meningitis and osteomyelitis. Platelet functions were examined in seven of the children but no abnormalities were observed. Bone marrow aspiration of three children with pneumonia and empyema showed megakaryocytic hyperplasia. We found no correlation between thrombocytosis, neutrophilia, fever, the clinical course, complications, prognosis or treatment. Neither thromboembolic nor hemorrhagic phenomena were observed. PMID- 2235146 TI - Fatal varicella after a single course of corticosteroids. PMID- 2235147 TI - Aspergillus osteomyelitis in a child treated for acute lymphoblastic leukemia. PMID- 2235148 TI - Pseudallescheria boydii and brain abscesses. PMID- 2235149 TI - Diabetes insipidus as a complication of neonatal group B streptococcal meningitis. PMID- 2235151 TI - Histoplasmosis after multiple trauma. PMID- 2235150 TI - Dipylidium caninum, an underrecognized infection in infants and children. PMID- 2235152 TI - Hyperammonemia and neonatal herpes simplex pneumonitis. PMID- 2235153 TI - Use of antibiotics in neonates weighing less than 1200 g. PMID- 2235154 TI - Fatal adenovirus disease and human immunodeficiency virus infection. PMID- 2235155 TI - Diagnosis of Lyme arthritis. PMID- 2235156 TI - Antibiotics for respiratory syncytial virus infection. PMID- 2235157 TI - The tragedy of toxoplasmosis. PMID- 2235158 TI - Herpes simplex virus infections. PMID- 2235159 TI - Pediatric acquired immunodeficiency virus syndrome. PMID- 2235160 TI - Syphilis. PMID- 2235161 TI - Varicella in the womb and beyond. PMID- 2235162 TI - Subclinical infection as a cause of preterm delivery. PMID- 2235163 TI - Bacteriology of neonatal sepsis. PMID- 2235164 TI - Group B streptococcal infections. PMID- 2235165 TI - Adjuncts to the therapy of bacterial meningitis. PMID- 2235166 TI - Current antibacterial therapy for neonatal sepsis and meningitis. PMID- 2235167 TI - Management of chronic middle ear effusion with prednisone combined with trimethoprim-sulfamethoxazole. AB - Fifty-three patients were enrolled and evaluable in a randomized, double-blinded controlled clinical trial comparing prednisone for 7 days plus trimethoprim sulfamethoxazole (TMP/SMZ) for 30 days vs. TMP/SMZ alone in treating chronic middle ear effusion (MEE). Clearing of the effusion in both ears or in one when only one was involved was called complete resolution; clearing in one of two affected ears was called partial resolution. The outcomes 2 weeks after initiation of therapy of 26 patients initially treated with prednisone plus TMP/SMZ were complete resolution in 20, partial resolution in three, and unchanged in three. The outcomes in 27 patients initially treated with TMP/SMZ alone were complete resolution in eight, partial resolution in three, unchanged in 13 and development of acute otitis media in three (P less than 0.01 for complete resolution). Two weeks after initiation of therapy, patients with a MEE that failed to clear were crossed over to the alternative regimen. Overall 29 of 41 patients (71%) who received oral prednisone plus TMP/SMZ initially or after the crossover had complete resolution of their middle ear effusion at 2 weeks after starting prednisone and TMP/SMZ. Five of 35 (14%) patients treated with prednisone plus TMP/SMZ and one of six (17%) patients treated with TMP/SMZ alone who had complete resolution at 4 weeks required subsequent referrals for tympanostomy tubes. A course of prednisone for 7 days plus TMP/SMZ for 30 days with monthly follow-up should be considered in children with MEE persisting beyond 6-8 weeks before referral for tympanostomy tube placement. PMID- 2235168 TI - Central nervous system tuberculosis in children: a review of 30 cases. AB - The medical records of 30 children with central nervous system tuberculosis (CNS tuberculosis) who were treated between March, 1976, and February, 1989, were reviewed. All had cranial computerized tomography scans at presentation. The mean cerebrospinal fluid leukocyte count was 200/mm3, protein 239 mg/dl, glucose 25 mg/dl and CSF/serum glucose ratio 21%. Mantoux skin tests with 5 tuberculin units were greater than or equal to 10 mm induration in 50%, and chest radiographs were positive in 40% of patients. Hydrocephalus was demonstrated by cranial computerized tomography in all 30 patients (100%). Cranial computerized tomography scan demonstrating hydrocephalus is a sensitive radiographic nervous system tuberculosis and should be part of the early evaluation of children with suspected central nervous system tuberculosis. PMID- 2235169 TI - Immunoglobulin G subclasses in serum and circulating immune complexes in patients with Kawasaki syndrome. AB - IgG subclass concentrations in sera of 17 patients with Kawasaki syndrome were determined. Significantly increased IgG1 (P less than 0.001) and IgG3 (P less than 0.001) were found in the patients compared with 22 age-matched healthy children, whereas IgG2 and IgG4 were normal or slightly decreased. IgG immune complexes were measured by protein A-enzyme-linked immunosorbent assay (ELISA) combined polyethylene glycol precipitations. Eight of 17 patients (47.1%) were found to have circulating immune complexes (CIC) values above the normal control range (geometric mean +2 SD). IgG subclass composition in CIC was analyzed. The subclasses in CIC were predominantly IgG1 and IgG3. Because the antibody responses to different antigens exhibit IgG subclass restriction, it would suggest that the change of serum and CIC IgG subclasses in Kawasaki syndrome may have relevance to the pathogenesis of the disease. PMID- 2235170 TI - The use of prophylactic furazolidone to control a nosocomial epidemic of multiply resistant Salmonella typhimurium in pediatric wards. AB - The nosocomial spread of enteric pathogens is often difficult to control in overcrowded pediatric wards. During 1983 and 1984, despite cohorting of patients and enforced hand washing, more than 200 cases of nosocomial multiply resistant Salmonella typhimurium phage type R-9 were observed on two adjacent pediatric wards. Most cases occurred during the summer months. After 19 new cases were detected early in the summer of 1985, oral administration of furazolidone throughout their entire hospital stay (2.5 mg/kg twice daily) was recommended for all subsequently hospitalized infants. Among the 114 (65%) infants who were appropriately treated, only one additional case (1%) was detected. In contrast 11 (19%) cases occurred among the 59 infants who were inappropriately treated: 5 of 35 (14%) of those who were not treated and 6 of 24 (25%) in whom treatment with furazolidone was delayed greater than 24 hours (P less than 0.001 between the appropriately and inappropriately treated groups). In pediatric wards where infection control measures cannot be optimally applied, prophylactic furazolidone administration may be helpful in preventing the spread of enteric pathogens. PMID- 2235171 TI - Safety evaluation of PRP-D Haemophilus influenzae type b conjugate vaccine in children immunized at 18 months of age and older: follow-up study of 30,000 children. AB - We evaluated the safety of the PRP-D conjugate Hib vaccine (ProHIBit, Connaught) in 29,309 children vaccinated at 18-60 months of age in the Southern California Kaiser Permanente medical clinics during the period April 1, 1988, to July 31, 1989. Surveillance for potential reactions involved postcard questionnaires, telephone surveys, reports of Kaiser staff and review of hospitalizations and covered two periods following immunization: (1) the first 48 hours and (2) days 2 through 30. Surveillance for invasive Hib disease involved the above methods in addition to systematic reviews of laboratory and hospital records through January 31, 1990. Rates of local and systemic reactions within 48 hours of vaccination with PRP-D alone were low (less than or equal to 2% for fever greater than 102 degrees F, local redness or swelling) and similar to those previously reported after vaccination with PRP. Hospitalization and seizures (0.15% and 0.09% of vaccinated children, respectively) occurring within 1 month of immunization appeared to be unrelated to vaccination. One 29-month-old child had onset of a fatal episode of Hib sepsis/meningitis within 48 hours of vaccination. Also, a 30 month-old child developed Hib meningitis 10 months after PRP-D vaccination. We conclude that PRP-D is safe when given alone or in combination with other childhood vaccines between 18 and 60 months of age. PMID- 2235172 TI - An epidemic outbreak of cryptosporidiosis: a prospective community study from Guinea Bissau. AB - In the first year of a prospective community study of childhood diarrhea conducted in a semiurban area in the capital of Guinea Bissau, Cryptosporidium sp. was found in 73 (6.0%) of 1216 episodes of diarrhea. The parasite was the second most prevalent intestinal parasite, and the only one significantly associated with diarrhea (OR = 2.79, P = 0.0006). The seasonal distribution was striking, with a peak prevalence in the beginning of the rainy season (May 17.6%) when an epidemic outbreak of diarrhea started. The prevalence was highest in children younger than 18 months, an age at which prevalences of other intestinal parasites were low. This reverse age pattern may possibly be explained by the small infective dose needed to create severe infections, by air-borne transmission and by the development of protective immunity. PMID- 2235173 TI - Pre-discharge immunization among hospitalized Filipino children. AB - Identifying opportunities to vaccinate eligible children is one way to boost rates of immunization especially in countries with low immunization coverage and where convalescence from infectious illness is a contraindication to vaccination. To determine the safety and immunogenicity of diphtheria-tetanus toxoid-pertussis and oral polio immunization, 210 convalescing infants and children and community controls, comparable image and nutritional status, were studied. Using the pertussis agglutination and poliovirus neutralization tests, quantitative serologic responses were compared in the two study groups. No significant differences in the incidence rates of febrile reactions (23% in controls; 28% in convalescents) of local reactions (92% in controls; 87% in convalescents) and of seroconversion (P greater than 0.05) were noted between the two groups. Our investigation suggests that infants and children convalescing from infectious illnesses can be safely and effectively vaccinated. This study further suggests that hospitalization provides an opportunity to vaccinate such children. PMID- 2235174 TI - Maternal immunization. PMID- 2235176 TI - A clue (tip-off) to urinary infection with Candida. PMID- 2235175 TI - Clostridium sordellii infection and toxin neutralization. PMID- 2235178 TI - Lyme disease presenting as hepatitis and jaundice in a child. PMID- 2235177 TI - Eustachian tube dysfunction in children with streptococcal pharyngitis. PMID- 2235179 TI - Bacteriology of retropharyngeal abscess in children. PMID- 2235180 TI - Haemophilus influenzae type B abscess after diphtheria-tetanus toxoids-pertussis immunization. PMID- 2235181 TI - Interstitial pneumonia and alpha-hemolytic Streptococcus sepsis in a child with malignancy who recently received cytosine arabinoside. PMID- 2235182 TI - False-positive Chlamydia immunoassays. PMID- 2235183 TI - Prophylactic zidovudine for a child after human immunodeficiency virus needlestick exposure. PMID- 2235184 TI - The Pediatric Infectious Diseases Society 1990 awards. PMID- 2235185 TI - Perinatally acquired human immunodeficiency virus infection. PMID- 2235186 TI - Case-control study of Cryptosporidium parvum infection in Peruvian children hospitalized for diarrhea: possible association with malnutrition and nosocomial infection. AB - A retrospective, hospital-based case-control study was used to investigate whether there were any clinical characteristics that could distinguish Cryptosporidium parvum-infected children with diarrhea from other non-C. parvum infected children with diarrhea. Ten percent (24 of 248) of children admitted to a rehydration ward at Cayetano Heredia University Hospital, Lima, Peru, were infected with C. parvum. The 24 patients infected with C. parvum (cases) were matched to an equal number of noninfected patients (controls). C. parvum-infected patients were more likely to be malnourished than were children without this infection (P less than 0.05). Also nosocomial infection caused by C. parvum occurred in three severely malnourished patients, two of whom died. No other clinical or laboratory characteristics were found that would distinguish children with diarrhea caused by C. parvum from other children with diarrhea. In children hospitalized for diarrhea C. parvum infection occurs most frequently in malnourished children. PMID- 2235187 TI - Immunogenicity of Haemophilus b conjugate vaccine (meningococcal protein conjugate) in children with prior invasive Haemophilus influenzae type b disease. AB - Children younger than 2 years of age with previous invasive Haemophilus influenzae (Hib) type b disease may not develop protective antibodies to antigens of Hib and may be at risk of developing a second episode of Hib disease. Twenty three children with prior Hib disease were immunized with Haemophilus b conjugate vaccine (meningococcal protein conjugate). Children 12 to 24 months of age were given one dose of vaccine and children younger than 12 months of age were given 2 doses 2 months apart. Antibody to the polysaccharide capsule of Hib (PRP) was measured by radioimmunoassay. Eighteen children had preimmunization serum antibody concentrations less than 0.150 micrograms/ml. All 18 children responded with greater than 0.150 micrograms/ml of antibody after a single dose of vaccine. Only 1 of the 23 children had a preimmunization serum antibody concentration greater than 1.000 micrograms/ml. Seventeen children ultimately responded with greater than 1.000 micrograms/ml of antibody (P less than 0.0001), concentrations of antibody thought to correlate with protection. Haemophilus b conjugate vaccine (meningococcal protein conjugate) is immunogenic in children with invasive Hib disease. Children younger than 2 years of age with invasive Hib disease should be subsequently immunized with a Hib conjugate vaccine. PMID- 2235188 TI - Clinical features of adenovirus enteritis: a review of 127 cases. AB - We retrospectively analyzed the clinical features of 127 hospitalized pediatric patients whose fecal samples were positive for adenovirus (Ad) by electron microscopy during an 18-month period. Serotyping results obtained by microneutralization tests and restriction endonuclease analysis were available for 105 of 127 cases. There were 69 males and 58 females and 94% of patients were less than 4 years of age. The average body temperature was 38 degrees C rectal (range, 36.2-40.8 degrees C) with an average duration of fever of 1.6 days. The average duration of clinical illness was 8.8 days (range, 1 to 32 days). Although Ad 40 and Ad 41 were isolated in the majority of cases (59 of 105 (56%], Ad 31 was associated with 18 of 105 cases (17%). Of the 18 cases associated with Ad 31, 14 were nosocomial and associated with diarrhea. Our survey confirms the importance of fastidious enteric Ad in infantile diarrhea (Ad 40, Ad 41) and suggests that Ad 31 produces a clinical syndrome indistinguishable from that caused by Ad 40 and Ad 41. The occurrence of Ad enteritis in patients admitted for unrelated illnesses well after initial hospitalization suggests that Ad is also an important cause of nosocomial enteritis in our hospital. PMID- 2235189 TI - Pneumococcal endocarditis in infants and children: report of a case and review of the literature. PMID- 2235190 TI - Central nervous system melioidosis in children. PMID- 2235191 TI - Candida albicans placentitis and funisitis: early diagnosis of congenital candidemia by histopathologic examination of umbilical cord vessels. PMID- 2235193 TI - Limp as a presenting sign of meningitis. PMID- 2235192 TI - Campylobacter infection in the neonate: case report and review of the literature. PMID- 2235194 TI - External ophthalmomyiasis in an urban infant. PMID- 2235195 TI - Catheter-related sepsis refractory to antibiotics treated successfully with adjunctive urokinase infusion. PMID- 2235196 TI - Stomatococcus mucilaginosus infections in children with leukemia. PMID- 2235197 TI - Adverse reactions to ribavirin. PMID- 2235198 TI - Haemophilus influenzae type b resistant to ampicillin and chloramphenicol. PMID- 2235199 TI - Treatment of congenital toxoplasmosis. PMID- 2235201 TI - An industrial hygiene approach to controlling nonpatient exposure to ribavirin aerosol. PMID- 2235200 TI - Benzathine penicillin G for the treatment of infants and children with pneumonia. PMID- 2235202 TI - Reproductive risk assessment with occupational exposure to ribavirin aerosol. PMID- 2235203 TI - Studying the safety of ribavirin in human pregnancy. PMID- 2235204 TI - Pulmonary function testing in infants with respiratory syncytial virus bronchiolitis requiring mechanical ventilation. PMID- 2235205 TI - Safety of ribavirin with mechanical ventilation. PMID- 2235206 TI - Adverse drug reactions: United States experience. I. PMID- 2235207 TI - Prioritizing research questions on the safety of ribavirin in the treatment of respiratory syncytial virus infections. PMID- 2235208 TI - Clinical studies with ribavirin. PMID- 2235209 TI - Study design considerations for ribavirin: efficacy studies. AB - Five placebo-controlled double-blind studies, each including approximately 30 subjects, have addressed the question of the effect of aerosolized ribavirin on the course of RSV lower respiratory infection in infancy. The fact that each was able to establish a beneficial effect despite the small number of subjects studied is convincing evidence that such an effect exists. The studies from Rochester using oximetry and an analog illness severity scale indicate that this effect is both statistically significant and clinically relevant. These tools are reliable and easily applicable measures for multicenter studies when illness severity is selected as an outcome measure. Characteristics that should be taken into consideration when assigning experimental groups include age, sex, a history of prematurity or underlying conditions and arterial oxygen saturation. Future studies will address additional questions about the efficacy of ribavirin, such as its role in critically ill children, the economic benefits of its use in terms of duration of hospitalization, the usefulness of early treatment of RSV disease in high risk infants, and the impact of treatment on long-term consequences of RSV infection. These studies may require outcome variables and subject selection strategies different from those used in earlier studies. PMID- 2235210 TI - New data on clinical efficacy of ribavirin. PMID- 2235211 TI - Early ribavirin aerosol treatment of respiratory syncytial virus infection in high-risk children. PMID- 2235212 TI - Clinical use of ribavirin in the future. PMID- 2235213 TI - Developmental toxicity and safety evaluations of ribavirin. PMID- 2235214 TI - Ribavirin pharmacokinetics. PMID- 2235215 TI - Hemodynamic alterations in patients treated with ribavirin. PMID- 2235216 TI - Environmental exposure to ribavirin aerosol. PMID- 2235217 TI - Primary care: the future for pediatric education. PMID- 2235218 TI - Prevalence of human immunodeficiency virus seropositivity in pediatric emergency room patients undergoing phlebotomy. AB - Information on the prevalence of human immunodeficiency virus (HIV) infection among children and adolescents requiring medical care is sparse. A small but significant risk of seroconversion occurs in health care workers who handle blood and body fluids of patients infected with HIV. The prevalence of HIV seropositivity in children who had phlebotomy as part of emergency care was measured. Of 749 blood samples, 21 (2.8%) tested positive for HIV antibody by enzyme-linked immunosorbent assay and Western Blot analysis: 14 samples from 6 patients with hemophilia, 6 from 3 patients with acquired immunodeficiency syndrome/acquired immunodeficiency syndrome-related complex, and 1 from a patient with asthma. Of these 21 blood samples, 10 were from 4 children previously known to be HIV positive, 4 were from patients with a known parental risk factor, and 16 were from patients with known history of blood transfusion. One sample was from a children with unknown HIV status and no documented risk factors. Procedures included 9 venipunctures, 17 intravenous line placements, 1 lumbar puncture, and 1 pelvic examination. Most patients with HIV seropositivity had been known to be HIV seropositive or at significant risk for HIV seropositivity. Although the potential risk to health care workers from children without known risk factors for HIV seropositivity was small in this population, the currently recommended infection-control precautions should always be observed. PMID- 2235219 TI - Access to medical care for children and adolescents in the United States. AB - To evaluate access to health care for American children and adolescents, a telephone survey of a national random sample of households was conducted in which 2182 children 17 years or younger were studied. Approximately 10% had no medical insurance; 10% had no regular source of care; and 18% identified emergency rooms, community clinics, or hospital outpatient departments as their usual site of medical care. Children who were uninsured, poor, or nonwhite were less likely to have seen a physician in the past year (P less than .001), and uninsured children were less likely to have up-to-date immunizations. Logistic regression analyses revealed that poor, uninsured, or nonwhite children less frequently had a regular source of care; more frequently used emergency rooms, community clinics, and hospital outpatient departments as their regular providers; and more frequently encountered financial barriers to health care. Low-income or nonwhite children had much less access to care compared with children from more affluent or white families, independent of insurance status or health status. PMID- 2235220 TI - Children riding in the back of pickup trucks: a neglected safety issue. AB - Motor vehicle-related trauma is the leading cause of death in children in the United States. All states have pediatric restraint requirements for passenger vehicles to help prevent these deaths and injuries. Only a few states, however, possess safety laws or restrictions for passengers who ride in the back of pickup trucks. A retrospective review of medical records for a 40-month period revealed 40 patients whose injuries were a direct result of being a passenger in the cargo area (bed) of a pickup truck. Their injuries and other pertinent data are discussed. Representatives from the Highway Safety Commission of each state were surveyed about their specific highway safety laws. The responses revealed that all states and the District of Columbia have child restraint requirements for passenger automobiles, 34 states have adult restraint laws, but only 17 states have any type of restriction for passengers riding in the back of pickup trucks. Seventy-one percent of the states with pickup truck regulations include only the preschool-age child. Data from the National Highway Traffic Safety Administration concerning pickup trucks and passenger fatality are presented and discussed. PMID- 2235221 TI - Hair dryer burns in children. AB - Three children with burn injuries caused by home hair dryers are described. In one patient the injury was believed to be accidental, and in the other two cases the injuries were deliberately caused by a caretaker. The lack of prior experience with hair dryer burns initially led to suspicion of other causes. The characteristics of each case aided in the final determination of accidental vs nonaccidental injury. These cases prompted testing of home hair dryers to determine their heat output. At the highest heat settings, the dryers rapidly generated temperatures in excess of 110 degrees C. After the dryers were turned off, the protective grills maintained sufficient temperatures to cause full thickness burns for up to 2 minutes. These cases and the results of testing demonstrate that hair dryers must be added to the list of known causes of accidental and nonaccidental burns in children. PMID- 2235222 TI - Transbronchial biopsies in children after heart-lung transplantation. AB - Sixty transbronchial biopsies have been performed in eight children after heart lung transplantation. The selection of fiber-optic bronchoscope or a small (4 mm; 30 cm) rigid bronchoscope was made according to the size of endotracheal tube required at surgery. If the endotracheal tube was size 7.5 or greater, a fiber optic bronchoscope was used, whereas if the endotracheal tube size was below 7, a rigid bronchoscope was used. For the diagnosis of lung rejection, the histology of biopsies revealed a sensitivity of 91% and specificity of 69% (similar to the result in adults). The histology also distinguished lung infection from rejection. Complications included three pneumothoraces and two clinically significant episodes of hemorrhage, one of which led to a cardiorespiratory arrest, which may have been caused by hypoxia. As a result, arterial oxygen saturation is now monitored during the procedure using a pulse oximeter. PMID- 2235223 TI - Self-induced urinary tract infection in school-age boys. AB - This study focuses on a consecutive series of 31 boys, aged 5 years 3 months to 14 years 9 months, who had a first diagnosed urinary tract infection. A questionnaire administered after diagnosis revealed that 10 of these boys injected water into their urethra while taking a bath in the few days preceding the onset of infection. Neither presenting symptoms nor urine tests can distinguish self-inflicted infections from infections occurring spontaneously. However, no urinary tract malformations were detected among the boys with a history of urethral manipulation whereas one third of the other 21 boys had anomalies. If these data are confirmed by other studies, complete imaging investigation could then be avoided in such cases. It could also become possible to prevent a number of urinary tract infections in school-age boys by warning parents and children of the serious risks of self-instrumentation. PMID- 2235224 TI - Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome. AB - Previous prognostic studies of infants with intrauterine growth retardation (IUGR) have not adequately considered the heterogeneity of IUGR in terms of cause, severity, and body proportionality and have been prone to misclassification of IUGR because of errors in estimation of gestational age. Based on a cohort of 8719 infants with early-ultrasound-validated gestational ages and indexes of body proportionality standardized for birth weight, the consequences of severity and cause-specific IUGR and proportionality for fetal and neonatal morbidity and mortality were assessed. With progressive severity of IUGR, there were significant (all P less than .001) linear trends for increasing risks of stillbirth, fetal distress (abnormal electronic fetal heart tracings)O during parturition, neonatal hypoglycemia (minimum plasma glucose less than 40 mg/dL), hypocalcemia (minimum Ca less than 7 mg/dL), polycythemia (maximum capillary hemoglobin greater than or equal to 21 g/dL), severe depression at birth (manual ventilation greater than 3 minutes), 1-minute and 5-minute Apgar scores less than or equal to 6, 1-minute Apgar score less than or equal to 3, and in-hospital death. These trends persisted for the more common outcomes even after restriction to term (37 to 42 weeks) births. There was no convincing evidence that outcome among infants with a given degree of growth retardation varied as a function of cause of that growth retardation. Among infants with IUGR, increased length-for-weight had significant crude associations with hypoglycemia and polycythemia, but these associations disappeared after adjustment for severity of growth retardation and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235225 TI - Development and validation of an index for scoring baseline respiratory disease in the very low birth weight neonate. Severity Index Development and Validation Panels and Newborn Lung Project. AB - An accurate description of the population at risk for neonatal chronic lung disease is clearly of prime importance for comparative studies and the planning of interventions. Attempts to explain variations in chronic lung disease rates in such studies have been compromised by lack of a way of estimating the severity of the initial pulmonary disease as a risk factor. Therefore, a severity index was developed for use in very low birth weight (less than 1501 g) neonates. Special emphasis was placed on applicability of the index in the multicenter observational setting. Development followed a clinician panel approach, with the resulting index designed to capture clinical judgment of severity. The index was validated prospectively on neonates in a neonatal intensive care unit, and retrospectively using charts from nine hospitals nationwide. Correlations of the index with clinical judgment in the two samples were .95 and .93, respectively. In an additional validation the index combined with birth weight correctly predicted oxygen dependence status at 30 days in 36 of 42 neonates consecutively admitted to five neonatal intensive care units (P = .002). Birth weight and the severity index contributed about equally to the prediction, and therefore they seem to represent partly independent components of baseline propensity for prolonged oxygen dependence. PMID- 2235226 TI - Dexamethasone effects on the hospital course of infants with bronchopulmonary dysplasia who are dependent on artificial ventilation. AB - A randomized double-blind placebo-controlled trial was conducted to evaluate the effects of enterally administered dexamethasone on the hospital course of infants with bronchopulmonary dysplasia. A total of 23 infants with a birth weight less than 1500 g who were dependent on artificial ventilation 3 to 4 weeks of age received dexamethasone (n = 12) or saline placebo (n = 11). Dexamethasone (0.5 mg/kg per day) was given in tapering doses for 7 days followed by hydrocortisone (8 mg/kg per day) which was progressively reduced for a total of 17 days of therapy. Infants who received dexamethasone required less oxygen on days 8 and 17 (P less than .05) and were more likely to extubate 8 days after therapy than infants in the control group (respectively 8/12 vs 3/11 infants, P less than .05; P = .12 after Yates correction). The use of dexamethasone significantly shortened median duration of mechanical ventilation (4 vs 22 days, P less than .05) but had no effect on length of oxygen therapy, hospitalization, home oxygen therapy, occurrence and severity of retinopathy of prematurity, rate of growth, and mortality. No significant complications resulted from dexamethasone therapy. Measurements of plasma dexamethasone levels confirmed the absorption of drug from the gastrointestinal tract (23.7 ng/mL in dexamethasone vs 4.6 ng/mL in the control group, P less than .05). Dexamethasone administration resulted in short term improvements in pulmonary function but did not ameliorate the hospital course of infants with bronchopulmonary dysplasia. PMID- 2235228 TI - Prolonged maternal fluid supplementation in breast-feeding. AB - A randomized, crossover study design was used to evaluate the effect of prolonged maternal fluid supplementation on the milk supply of breast-feeding women. A total of 19 well-nourished women whose infants were solely breast-fed and thriving were enrolled when their infants were 90 to 120 days of age. Of this group, 15 women consumed at least a 25% increase in fluids above baseline for 7 days. Mean daily milk production was 767 +/- 178 mL for the baseline period and 744 +/- 138 mL for the increased fluid period. There was no significant change in milk production between baseline and increased fluid periods. No significant linear relationship between the percentage increase in fluid intake and percentage change in milk production was found. PMID- 2235227 TI - Predicting risk for bronchopulmonary dysplasia: selection criteria for clinical trials. AB - Early identification of neonates in whom bronchopulmonary dysplasia is most likely to develop permits appropriate enrollment into clinical trials testing early intervention therapies for the prevention or treatment of bronchopulmonary dysplasia. Analysis of 160 neonatal intensive care unit survivors to 28 days revealed that supplemental oxygen requirement at 28 days could be predicted by a logistic regression including (1) birth weight, gestational age, 5-minute Apgar score, and peak inspiratory pressure at 12 hours for 12-hour-old neonates and (2) birth weight, gestational age, peak inspiratory pressure at 12 hours, and mean airway pressure at 10 days for 10-day-old neonates. These two regression analyses were applied prospectively to three new data sets totaling 238 neonates to test their predictive ability. Neonates were classified into low-, moderate-, or high risk groups on the basis of their predicted probability of requiring oxygen supplementation at 28 days; low = probability of less than 25%, moderate = probability of 25% to 75%, and high = probability greater than 75%. Although these populations were demographically distinct from the original group, the regression analyses performed well. The regression analysis for 12 hours of age classified 125 neonates at low risk of whom 9% required supplemental oxygen at 28 days, and the regression analysis for 10 days classified 141 neonates at low risk of whom 7% required supplemental oxygen. The 12-hour regression analysis classified 80 neonates at moderate risk of whom 33% required supplemental oxygen at 28 days and the 10-day regression analysis classified 49 neonates at moderate risk of whom 24% required supplemental oxygen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235229 TI - Breast-feeding rates among black urban low-income women: effect of prenatal education. AB - Many factors are associated with low breast-feeding rates among black low-income women. This study examines whether, despite such factors, health professionals' prenatal education of black poor women is associated with increased breast feeding rates. Black women born in the United States who attended a midwives prenatal clinic (N = 159) were randomly assigned to two types of prenatal education or were followed up in a control group. All women were interviewed on entry into the study and after delivery of their infants. Women assigned to group classes attended at least one session discussing myths, problems, and benefits of breast-feeding. Women assigned to individual prenatal counseling spoke with a pediatrician or nurse practitioner, who discussed breast-feeding topics similar to those covered in the classes. Women in the control group received no additional prenatal education. The three study groups had significantly different percentages of women who breast-fed (controls 22%, classes 46%, individual sessions 53%). Higher percentages of women in the study groups carried out their prenatal plans to breast-feed (controls 50%, classes 86%, individual sessions 62%) or breast-fed despite prenatal plans to bottle-feed (controls 10%, classes 26%, individual sessions 48%). After multivariable analysis controlling for age, prenatal plans to breast-feed, prior breast-feeding experience, perceived support for breast-feeding, education, gravidity, and employment plans, women in intervention groups had a higher likelihood of breast-feeding than control subjects. These findings suggest that an increase in relatively simple, not-too time-consuming educational efforts in institutions and offices serving black low income women might yield significant narrowing of the gap in breast-feeding rates between white affluent women and black low-income women. PMID- 2235230 TI - Surfactant replacement therapy with a single postventilatory dose of a reconstituted bovine surfactant in preterm neonates with respiratory distress syndrome: final analysis of a multicenter, double-blind, randomized trial and comparison with similar trials. The Surfactant-TA Study Group. AB - The effects of a single dose of surfactant TA were assessed in premature neonates (birth weight 750 to 1749 g) with respiratory distress syndrome (RDS) in a multicenter, double-blind, randomized clinical trial. Only neonates with surfactant deficiency and without ultrasonographic evidence of intracranial hemorrhage greater than or equal to grade II were enrolled. Fifty-four patients received surfactant (100 mg of phospholipid per kilogram of body weight) and 46 patients received an air placebo within 8 hours of life. Treatment with this surfactant resulted in a significant reduction in the severity of RDS with a concomitant increase in the proportion of neonates with mild disease. The frequency of pulmonary interstitial emphysema and of pneumothorax was significantly lower in treated neonates compared with control neonates (2% vs 26%, P = .0008, and 7% vs 39%, P = .0004, respectively). The frequency of intracranial hemorrhage was significantly lower in the surfactant group compared with the control group (20% vs 54%, P = .0008) and was also reduced for the smallest neonates in the surfactant group (13% vs 73%, P = .00008). When categorized according to severity of intracranial hemorrhage and severity of bronchopulmonary dysplasia, the surfactant group was at a significant advantage (adjusted Cochran-Mantel-Haenszel X2 = 10.72, P less than .001 and X2 = 4.43, P = .036, respectively). The proportion of neonates surviving without intracranial hemorrhage and/or bronchopulmonary dysplasia was 63% in the surfactant group vs 26% in the control group (P = .0004); as for the smallest neonates, it was 58% in the surfactant group vs 4% in the control group (P = .0002). There were no differences between the groups with respect to the frequency of patent ductus arteriosus (46% vs 37%), pulmonary hemorrhage (6% vs 7%), necrotizing enterocolitis (0% vs 2%), sepsis (4% vs 2%), retinopathy of prematurity (13% vs 22%), or death (15% vs 22%). It is concluded that treatment with the single-dose surfactant regimen used in this study reduces the severity of respiratory distress during the 48 hours after treatment and decreases the major pulmonary morbidity and intracranial hemorrhage in premature neonates with RDS. Further studies are needed to determine whether (1) treatment at birth or as soon as after RDS is diagnosed and (2) the use of multiple dose of this surfactant would result in any additional benefits. PMID- 2235231 TI - Pediatric acquired immunodeficiency syndrome: an unusually high incidence of twinning. AB - Surveillance data on incidence of twins among reported cases of pediatric AIDS in New York City are presented. Most pairs are concordant for HIV infection. Three discordant pairs have been described elsewhere. Possible reasons for the association are discussed, including the most likely explanation that twins show symptoms early and are overrepresented in the early years of surveillance of pediatric AIDS. PMID- 2235232 TI - Failure of a nursing infant to thrive after the mother's gastric bypass for morbid obesity. PMID- 2235233 TI - Drug prescribing in pediatrics: challenges for quality improvement. PMID- 2235234 TI - Economy, convenience, and safety: can we have it all? Some thoughts on the occasion of the fortieth anniversary of the Committee on Injury and Poison Prevention. PMID- 2235235 TI - Predicting risk for bronchopulmonary dysplasia. PMID- 2235236 TI - Screening for neuroblastoma in infants: investigate or implement? PMID- 2235237 TI - American Academy of Pediatrics Committee on Infectious Diseases: Haemophilus influenzae type b conjugate vaccines: immunization of children at 15 months of age. PMID- 2235238 TI - American Academy of Pediatrics Committee on Sports Medicine: Risks in distance running for children. PMID- 2235239 TI - American Academy of Pediatrics Committee on Sports Medicine: Strength training, weight and power lifting, and body building by children and adolescents. PMID- 2235240 TI - Sports deficit disorder. PMID- 2235241 TI - Child abuse. PMID- 2235242 TI - Infant feeding and infectious disease. PMID- 2235244 TI - Pediatric emergencies. PMID- 2235243 TI - Fever and petechiae in children. PMID- 2235245 TI - The work of pediatric residents. PMID- 2235246 TI - Persistent pulmonary hypertension and ECMO. PMID- 2235247 TI - The NICHD phototherapy study. PMID- 2235248 TI - Identification of time-compressed sentential stimuli by good vs poor readers. AB - Ability of eight good and eight poor readers (in Grade 1, ages ranging from 6.7 to 7.4 yr.) to discriminate phonemic contrasts presented in 50% time-compressed sentential stimuli (Subtest 13 of the Carrow-Auditory Visual Abilities Test) was measured. Good readers exhibited a significantly higher over-all mean performance than poor readers on the time-compressed task. Effects of time-compression on the perception of manner, place, voicing and frequency contrasts showed a similar pattern of errors for both groups of readers. Implications of the effects of auditory discrimination on reading abilities are discussed. PMID- 2235249 TI - A choice-reaction time task utilizing congruent and incongruent colour/word stimuli: another reaction to Stroop. AB - A choice reaction time task was devised, using incongruent colour/word (Stroop type) and congruent colour/word stimuli. A significant difference was found between reaction times to the two stimulus types with the Stroop-type stimuli eliciting longer reaction times. It is argued that traditional hypotheses about channel limitation can not explain this finding; the suggestion that the delay may lie in the decision-making process is put forward. PMID- 2235250 TI - Effect of the standard on size of the horizontal-vertical illusion. AB - 70 subjects participated in a study designed to replicate the 1968 claim of Gardner and Long that the horizontal-vertical illusion is larger with the vertical than with the horizontal as standard. The effect did not appear in Exp. 1 when subjects made judgments under both the reproduction and graded-series methods but did in a pilot study and in Exp. 2, although more strongly with the method of reproduction. PMID- 2235251 TI - Perception of unilateral weightbearing during unilateral and bilateral upright stance. AB - To compare the effect of stance (unilateral vs bilateral) and of weightbearing target (25%, 50%, 75%) on error in weightbearing perception, two groups, unilateral and bilateral, of 30 comparable subjects were tested. Weightbearing was measured while subjects stood on digital scales; bilateral stance was accomplished using two scales, and unilateral stance was accomplished using a walker and a single scale. The subject's error in perceiving weightbearing at each target level was assessed by taking the absolute value of the target percent weightbearing minus the mean actual percent weightbearing. The mean errors at the 25, 50 and 75% targets were 6.5, 3.2, 17.6% for the unilateral group and 3.1, 1.4, 3.8% for the bilateral group. A two-way analysis of variance indicated the magnitude of error differed between groups and target levels, with a greater over all error displayed by the unilateral weightbearing group. Our results suggest that adults are less accurate in judging weightbearing while standing on one, rather than on two, lower extremities. Clinicians should not expect patients to follow accurately instructions to weightbear at a specific percentage of full weight, particularly when using an assistive device to adjust weightbearing. PMID- 2235252 TI - Effects of walking on reaction and movement times among elders. AB - The purpose of this study was to examine the effects of a 6-wk. walking program on reaction times and movement times among 52 elders. Twenty-seven elderly, whose mean age was 71.8 yr. comprised the experimental group, and 25 elderly whose mean age was 71.8 yr. comprised the comparison group. The former subjects walked for 30 min. three times a week for 6 wk. while the latter maintained their normal activity. No significant differences in simple or choice reaction times and the associated movement times were found. To clarify the relationship of health and current and past physical activity, correlations of these with both simple and choice reaction times and movement times were examined. Except for the number of miles walked in a week, none of the correlations were significant. These results may not support previous findings that reaction and movement times were shorter with life-long participation in aerobic activity. However, the present study examined persons who were sedentary and were not involved in a life-long participation in aerobic exercise. Implications of these findings are discussed. PMID- 2235253 TI - Role of color in perception of attractiveness. AB - In this color study females reported a favorite color significantly more often than males. Males preferred bright colors significantly more than females, with a converse finding for preference for soft colors. The 276 subjects, when asked to evaluate the attractiveness of stimulus models in photographs, gave as the reason color significantly more often than style of clothing or facial expressions. Subjects significantly concurred with expert choices of recommended and nonrecommended colors in five of the six sets of photographs. This study lends credence that wearing recommended colors makes a difference in judgments of what looks best by subjects over the age of 12. PMID- 2235254 TI - Nonballistic coincident timing. AB - A nonballistic coincident timing task was used to assess to what extent retarded subjects could use spatial and temporal information to plan their movements. Subjects did not just respond to events but appeared able to modify/plan their responses, given sufficient time. PMID- 2235255 TI - Sex differences in severity of injury in attempted suicides who jump. PMID- 2235256 TI - Microgenetic patterns of adaptation on the Stroop task by patients with bronchial asthma and duodenal peptic ulcer. AB - Microgenetic patterns of adaptation on the Stroop task were assessed by means of the Serial Color-Word Test given 21 patients with bronchial asthma and 20 with duodenal peptic ulcer, who were compared with 41 normal controls matched for sex, age, and education. Two measures were calculated on each of the five trials of the test, one of linear change and one of nonlinear change in reading times. As predicted, patients presented more frequently patterns characterized by high nonlinear change and less frequently stabilized patterns (low linear and nonlinear change of reading speed). Linear and nonlinear change were then calculated on the five linear change scores and the five nonlinear change scores; again patients presented more frequently patterns characterized by high nonlinear change on both the linear change scores and nonlinear change scores and less frequently stabilized patterns. These findings indicate strong similarities between the adaptation patterns of patients with ulcer and asthma and the microgenetic patterns previously known to characterize neurotic and psychotic patients. Furthermore, scores on the Serial Color-Word Test also differentiated between ulcer and asthma groups. PMID- 2235257 TI - Responses of psychotic adolescents to PPVT-R items of human versus nonhuman content. PMID- 2235258 TI - Effect of orientation on visual and vibrotactile letter identification. AB - The effect of stimulus orientation of letters presented either visually or vibrotactually was examined to obtain basic information on sensory substitution using the tactile sense. The reaction time (RT) to identify the letters F and R presented in normal or mirror-image form at four orientations each was measured. In addition, conditions of 0 degree and 270 degrees of head rotation from vertical and arm rotation from the midline axis were employed. Data from 5 trained subjects showed that vibrotactile RTs were always longer than visual RTs. Stimulus rotation away from normal orientation increased visual RTs significantly but not vibrotactile RTs. Visual orientation effect then seemed to be determined by the body-coordinate system but not the vibrotactile orientation. Although further studies are warranted, from the results of this experiment, any convenient and constant stimulus orientation could be used with a wearable vibrotactile display system to exploit passive touch. PMID- 2235259 TI - Sport activity and personality as elements in preventing cancer and coronary heart disease. AB - Results are reported for 3 groups of healthy male probands, 318 in each group, matched for age and personality type on the Personality-Stress Questionnaire. One group was actively engaged in sports, one had discontinued former sporting activities, and one group had never taken part in regular sports. Follow-up after 13 yr. showed lowest mortality in those actively engaged in sport, highest mortality in those who had given up sport, with those who had never been engaged in sport intermediate. Prophylactic behaviour therapy was shown to reduce mortality of those who had given up sport to a significant extent but not to affect degree of retinal sclerosis. PMID- 2235260 TI - Encoding of colors in short-term memory. AB - A theory is proposed to explain results from prior experiments on release from proactive inhibition and the recall of colors or color names in short-term memory. It is assumed that colors are encoded in two ways, verbally and perceptually, while color names are encoded only verbally. Assuming that the release occurs when a new and different encoding is performed on changed material, it follows that release from proactive inhibition should occur with shifts from color names to colors but not with shifts in the opposite direction. These results were obtained in prior experiments. In the present experiment ambiguous colors were used to minimize the verbal encoding. As predicted, release from proactive inhibition was found with shifts from ambiguous colors to names as well as with shifts from names to the ambiguous colors. PMID- 2235261 TI - The prediction of death from cancer by means of personality/stress questionnaire: too good to be true? AB - Recent work by Grossarth-Maticek and Eysenck has suggested that there are personality traits which in combination can predict cancer in healthy probands with 81% accuracy. Many critics have considered this result "too good to be true." It is shown that earlier studies have given results not very different in accuracy, suggesting that such a criticism is unwarranted. PMID- 2235262 TI - Causal attributions of physical education majors and mentally retarded adults. AB - This exploratory study examined the causal attributions and expectancies of 51 physical education majors and 25 mentally retarded adults. The majors completed a written questionnaire concerning their causal attributions and expectancies for motor performance of the adults. The adults responded through an interview procedure regarding causal attributions and expectancies for their own motor performance. Analysis did not support the hypothesis that people make stable attributions about the performance of mentally retarded populations and subsequently maintain low expectancies. Previous experiences of failure did not diminish the expectancies of the adults for their own future success. PMID- 2235263 TI - Validity of the Estimated Learning Potential and other measures of learning potential. AB - The validity of the Estimated Learning Potential from the System of Multicultural Pluralistic Assessment was estimated using other measures of learning potential as criteria. In addition, correlations of traditional IQs with the learning potential measures were examined. The correlations between the Estimated Learning Potential and the criterion measures were low to moderate. Further, the traditional IQ was more strongly related to the learning potential measures than to the Estimated Learning Potential. Implications of these results, including the finding that learning potential should not be considered a unitary construct, were discussed. PMID- 2235264 TI - Mortality from suicide in follow-up studies of psychiatric patients. PMID- 2235265 TI - Perceptual inequality between two physically equal constant velocities. AB - When an object moves with an equal constant velocity before and after passing through a tunnel (or before and after a sudden acceleration--or deceleration--in the central part of its trajectory), the two velocities (the one preceding and the one following the tunnel or the sudden acceleration or deceleration) are perceived as different even if actually physically equal. Four experiments were carried out to underestimation of the second velocity (i.e., the one following the tunnel) when the first one (i.e., the one preceding the tunnel) is low, and an overestimation of the second one when the values of the first velocity are higher. An interpretation of the results is proposed, suggesting that an appearance effect (i.e., an apparent higher velocity at the beginning of the movement) could be for the perceptual inequality between the two physically equal constant velocities. PMID- 2235266 TI - Menninger's motives for suicide in genuine, simulated and hoax suicide notes. PMID- 2235267 TI - Stroop phenomena in the Vietnamese language: the case of Quocngu, Chunom and Chinese characters. PMID- 2235268 TI - Socioemotional functioning of creative preschoolers. AB - This study investigated the relationship between original thinking and socioemotional characteristics of 40 preschoolers, ranging in age from 44 to 68 mo. (M = 56.2 mo.). Socioemotional behavior was assessed by teachers on two ratings, the Kohn Social Competency and the Child's Behavior Traits scales. Creative potential was assessed by the Multidimensional Stimulus Fluency Measure which measures ideational fluency. Contrary to expectations, no statistically significant differences in psychosocial adjustment were found between the more and less creative preschoolers on a median split. A significant effect for sex was detected on six of seven socioemotional variables examined, with girls scoring higher than boys on over-all adjustment. Similarly, more positive attributes of preschool girls are indicated in areas of functioning that traditionally have been reported to be characteristic of boys. PMID- 2235269 TI - Overcrowding in prisons and rates of suicide and homicide. PMID- 2235270 TI - Relationship between academic placement and perception of abuse of the voice. AB - Informal polling of public school speech-language pathologists indicated that special education teachers referred more children for disorders of voice than did regular classroom educators. This study evaluated the effect of academic placement (regular or special education settings) upon children's and their teachers' ratings of abuse of the voice. Analysis showed the two groups of teachers' criteria for judging abusive vocal behaviors differed while the children's ratings from each setting did not differ. The special educators appeared to perceive their students' vocal behavior as more abusive possibly due to environmental constraints, training or the social affective interactions of their students. PMID- 2235271 TI - Anxiety, self-control and shooting performance. AB - 55 rifle shooters were administered state-trait anxiety and self-control questionnaires. Shooting performance was recorded on 7 competitive occasions. Analysis indicated shooting performance is dependent more on anxiety state than on anxiety trait and self-control. Highly skilled shooters were less anxious and performed better across all competitions than moderately skilled shooters but did not differ on self-control and anxiety trait. The assumption that increased anxiety negatively affects performance through the mediation of self-control should be further studied. PMID- 2235272 TI - Lack of sex differences with the Baldwin illusion. AB - Responses of college students (16 men and 16 women) to the Baldwin illusion showed a significant effect for size of square but not for sex. Findings are consistent with those reported previously by Porac, Coren, Girgus, and Verde for adults and for the oldest group of children tested by Pressey and Wilson. PMID- 2235274 TI - Effects of different attentional strategies and practice on motor efficiency. AB - The effect of different attentional strategies on motor efficiency, measured by reaction-response time components, has historically been based on memory-drum construct theory, which implied limited attention and motor-response processing. The present study contrasts these principles by using a recording system and automatic analysis of reaction-response parameters. A within-subject design allowed detailed observation of the frequency of each preparatory set within each parameter and with control of the effects of practice. Analysis indicates (a) practice changes the effects of the attentional strategies on the components of reaction response but not the actual movement; (b) the motor-set strategy produces shorter movement times and, inversely, higher motor reaction times; and (c) the motor-sensory set integrated strategy produces improvements on each component of the reaction response. These findings suggest the memory-drum construct theory needs revision and should be based on other attentional models. PMID- 2235273 TI - Syllogistic reasoning in Puerto Rican bilingual elementary school children. AB - The purpose of the present study was to measure the effects of language proficiency and grade (age) on the reasoning of Puerto Rican bilingual children in elementary school. 20 syllogisms were administered, 10 in English and 10 in Spanish, and accuracy of and strategy for solution were examined. Solutions were more often accurate, and the proportion of theoretical explanations given for them was higher in Spanish. Differences by grade were not significant except a higher proportion of theoretical explanations were given by children in Grade 5 for syllogisms in Spanish. PMID- 2235275 TI - Color CRT characterization presented solely in terms of the CIE system. AB - Color CRT characterization provides a convenient means of producing colors specified in terms of their chromaticity coordinates and luminances. It also simplifies the inverse procedure by enabling the determination of the chromaticities and luminances of displayed colors without direct measurement. This paper presents the characterization procedure entirely within the context of the well-known CIE system, a brief description of which is provided as background. This presentation is intended for those with access to a spectral radiometer but little familiarity with color specification or measurement. PMID- 2235276 TI - An intercultural comparison of immediacy among Japanese and Americans. PMID- 2235277 TI - The diagnostic value of cerebellar-vestibular tests in detecting learning disabilities, dyslexia, and attention deficit disorder. AB - Neurological and optokinetic measures of cerebellar-vestibular (CV) dysfunctioning were shown to be of significant diagnostic value in differentiating between learning disabled subjects and controls matched for chronological age, sex, handedness, IQ, and background (ns = 35). Although traditionally used electronystagmographic positional and caloric parameters were not similarly discriminating, quantitative measures of vertical nystagmus in various eyes-closed positions appeared to have diagnostic potential and were related significantly to such CV-determined neurological signs as positive monopedal Romberg. As a substantial majority of learning disabled (82.9%) evidenced ADD-like symptoms and since learning disabled subsamples with and without Attention Deficit Disorder (ADD) shared similar coexisting symptoms and CV signs, it appeared probable that learning disabilities and ADD were reflections of the same underlying CV determinants. PMID- 2235278 TI - Insulin and dextrose effects on fixed-interval behavioral thermoregulation in albino rats. AB - This study is a systematic replication of the effects of insulin doses on operant behavior reinforced (in an earlier study) by fixed-ratio schedules of microwave (MW) reinforcement. In this study, insulin and dextrose doses were administered (ip) prior to fixed-interval 2-min. schedules of MW reinforcement in rats tested in a cold environment. Six Sprague-Dawley rats were conditioned to regulate their thermal environment with 5-sec. exposures of MW radiation (SAR = 0.34 Watts/kg/(mW/cm2) under the FI-2' schedules. Humulin-regular insulin and 50% solutions of dextrose were administered (ip) alternately with saline control sessions for 8-hr. durations. A within-subjects, repeated-measures 4 x 8 x 3 factorial analysis of variance design showed that insulin doses suppressed operant responding for heat, which confirmed the results of the earlier study under a different schedule. In addition, high doses of dextrose had similar suppressing effects on operant responding for heat. The data are interpreted in terms of the discriminative properties of increased thermogenesis produced by the insulin and dextrose doses. The suppressing effects were more pronounced for the first two hours, yet they persisted for approximately six hours of the 8-hr. sessions. PMID- 2235279 TI - Computerized interpretation of the Luria-Nebraska Neuropsychological Battery: a pilot study. AB - Programs for the computer analysis and interpretation of neuropsychological test data have been developed in recent years. In this paper, a new computer program, with initial validation data, is presented. Diagnostic hit rate for brain damage was 80% (52 of 65). For the extent of brain damage the hit rate was 60% (12 of 20). When laterality was considered, the hit rate was 71% (10 of 14). These results are comparable with computer programs for data from the Halstead-Reitan Neuropsychology Test Battery. PMID- 2235280 TI - Subliminal stimulation and cognitive and motor performance. AB - The present experiment investigated whether subliminally exposed messages affect cognitive and motor performance and whether personality factors can explain interindividual differences in this respect. According to Silverman (1983), people have a symbiotic fantasy, that is, a need for symbiotic oneness with the mother figure. This need can temporarily be satisfied by a tachistoscopic exposure of the message "Mommy and I are one." By relieving the unconscious conflict, psychological tension is reduced. Using these notions, it was hypothesized that different measures of performance should be improved. The results indicate that both cognitive performance, in terms of the ability to interpret incomplete and fragmented pictures, and motor performance, in terms of the ability to follow a printed line with a stylus, is improved by this procedure compared to that of a control group exposed to the neutral message "People are walking." However, it was not possible to relate these changes to individual differences in terms of the individual's structure of his psychological defense system as measured by the Defense Mechanism Test (DMT). Other possible explanations are discussed. PMID- 2235281 TI - Effects of alcohol on cognitive performance measured with Stroop's Color Word Test. AB - An experiment was performed to test whether alcohol intoxication leads to cognitive disinhibition as measured by the Color Word Test. In psychoanalytic terms, it was hypothesized that alcohol would decrease secondary process functioning leading to disinhibition and so make it easier to perform a primary process function. 24 men and 24 women participated and were randomly assigned to an Alcohol group, a Placebo group or a Control group. The alcohol dose was 1.0 ml of 100% alcohol/kg body weight. No statistically significant differences were found on any of the three dependent measures, number of errors, number of hesitations and total time needed, except that men in the Alcohol group needed significantly longer time to complete the test. These results indicate that cognitive disinhibition is not valid as an explanation for alcohol-related changes in cognitive functioning. PMID- 2235282 TI - Cracks--of Kuhn and doom. PMID- 2235283 TI - Pigeon pattern perception: limits on perspective invariance. AB - Two experiments are reported in which the response of pigeons to perspective transformations of a pattern target was measured. In the first experiment an alphabet letter was taken as the pattern target (the 'positive') and the response to its perspective transforms was compared to the response to nontarget letters ('negatives') over the course of discrimination training. In the second experiment irregular quadrilaterals were used as positives and the responses to slight perspective deformations of the prototypes were compared to the responses to random transformations of the same magnitude under steady-state conditions. The amount of differential responding depended on the type of transformation. There was no differential response to targets rotated in the picture plane or around the horizontal axis in either experiment. There was differential response to small reductions and enlargements of the target. There was also differential response to translated targets, and this was seen irrespective of the amount of displacement. Results from targets rotated around the vertical axis were erratic, some target-plus-angle combinations elicited differential responding, but most did not. The erratic responses are attributed to symmetries in pattern elements that were abstracted as critical features. Pigeons therefore exhibit no true rotation invariance, limited size invariance, and complete shift invariance. It is argued that size invariance, but not position invariance, may depend on prior exposure to the alternatives. PMID- 2235284 TI - Stereo and motion cues in preattentive vision processing--some experiments with random-dot stereographic image sequences. AB - Low-level preattentive vision processing is of special interest since it seems the logical starting point of all vision processing. Exploration of the human visual processing system at this level is, however, extremely difficult, but can be facilitated by the use of stroboscopic presentation of sequences of random-dot stereograms, which contain only local spatial and temporal information and therefore limit the processing of these images to the low level. Four experiments are described in which such sequences were used to explore the relationships between various cues (optical flow, stereo disparity, and accretion and deletion of image points) at the low level. To study these relationships in more depth, especially the resolution of conflicting information among the cues, some of the image sequences presented information not usually encountered in 'natural' scenes. The results indicate that the processing of these cues is undertaken as a set of cooperative processes. PMID- 2235285 TI - Adaptation to optically-increased interocular separation under naturalistic viewing conditions. AB - Mirror spectacles which enhance binocular disparity by optically doubling the normal separation between the eyes were used to create conditions of combined perceptual and oculomotor conflict. Apparent depth and distance, as well as tonic accommodation, tonic vergence, and accommodative-vergence gain (response AC/A ratio), were assessed immediately before and after a 30 min exposure period of naturalistic viewing with the spectacles. Wearing the spectacles produced an increase in tonic vergence, and perceptual aftereffects consisting of increased apparent distance and depth. The results indicate that oculomotor conflict associated with enhanced interocular separation may be resolved through adaptation of tonic vergence, rather than through alteration of accommodative vergence gain. The results also demonstrate that perceptual conflict between disparity and multiple veridical depth cues does not necessarily produce adaptive modification of the relationship between binocular disparity and apparent depth. PMID- 2235287 TI - Perception of structure from two-, four-, or eight-dot oscillatory motion: restoration of rigidity with the aid of structural information. AB - The motion of two dots corresponding to the two endpoints of an oscillating rigid pendulum produces the perception of an elastic rod, not a rigid one. The possibility that structural information about a rigid object whose motion is simulated plays an important role in the perceptual restoration of the rigidity is examined. Two experiments are reported in which the motion of the endpoints of rigid objects (two endpoints for a rod, four for a sheet, and eight for a board) was displayed. Rigid structure was restored whenever structural information could be used to activate a knowledge data-base on the properties of the objects. PMID- 2235286 TI - How the visual system detects changes in the direction of moving targets. AB - To determine how the visual system represents information about change in target direction, we studied the detection of such change under conditions of varying stimulus certainty. Target direction was either held constant over trials or was allowed to vary randomly. When target direction was constant the observer could be certain about that stimulus characteristic; randomizing the target direction rendered the observer uncertain. We measured response times (RTs) to changes in target direction following initial trajectories of varying time and distance. In different conditions, the observer was uncertain about either the direction of the initial trajectory, or the direction of change or both. With brief initial trajectories in random directions, uncertainty about initial direction elevated RTs by 50 ms or more. When the initial trajectories were at least 500 ms, this directional uncertainty ceased to affect RTs; then, only uncertainty about the direction of change affected RTs. We discuss the implications of these results for (i) schemes by which the visual system might code directional change; (ii) the visual integration time for directional information; and (iii) adaptational processes in motion perception. PMID- 2235288 TI - Vernier acuity with opposite-contrast stimuli. AB - Vernier acuity has usually been tested with stimuli of the same contrast polarity (SC). This traditional vernier acuity was compared to that obtained with stimuli of opposite-contrast (OC) in which one target was brighter than the background and the other was darker. For both bar and dot targets vernier acuity with OC stimuli was about half as good as with SC stimuli. There were large individual differences in the size of the disadvantage with OC stimuli, although thresholds remained within the hyperacuity range. There were also individually-differing biases to see a dark vernier stimulus on one or the other side of a bright stimulus. Differences between OC and SC vernier acuities persisted over a wide range of interstimulus spacings, widths, and contrasts. At extremes of these spatial manipulations acuities became similar, but only because SC acuities were degraded to the level of OC acuities. Subjects showed little improvement in OC vernier acuity, even after 50,000 trials. It is concluded that finest judgements of spatial position arise in a level of the visual system at which light and dark stimuli are treated independently. PMID- 2235289 TI - Perceptual information for the timing of interceptive action. AB - Time-to-contact is an important quantity for controlling activities which involve the timing of interactions with objects and surfaces in motion relative to an observer. Two alternative means for obtaining perceptual information that might be used to obtain the time-to-contact required to correctly time an interaction have been contrasted: a method based on the perception of distance and velocity, and a method due to Lee involving a perceptual variable called tau. A monocular version of the first method is presented and shown to place a highly unrealistic and arbitrary limitation on the capabilities of the visual system. The second method is reviewed and its limitations discussed. Several means by which these limitations can be overcome are presented. Recently reported results from experiments which involved catching self-luminous balls in the dark are interpreted in terms of timing information available to the subject, and the notions of intermodal and multimodal timing information are introduced. Finally, the possibility that timing information is available to an observer which does not involve the variable tau is considered. It is concluded that many questions regarding the perception of time-to-contact remain unresolved and that much empirical research remains to be done. PMID- 2235291 TI - Perception and art: links with normal and abnormal brain function. Fifth international symposium of the Northern Eye Institute. Bristol, July 1989. Abstracts. PMID- 2235290 TI - Binaural and monaural localization of sound in two-dimensional space. AB - Two experiments were conducted. In experiment 1, part 1, binaural and monaural localization of sounds originating in the left hemifield was investigated. 104 loudspeakers were arranged in a 13 x 8 matrix with 15 degrees separating adjacent loudspeakers in each column and in each row. In the horizontal plane (HP), the loudspeakers extended from 0 degrees to 180 degrees; in the vertical plane (VP), they extended from -45 degrees to 60 degrees with respect to the interaural axis. Findings of special interest were: (i) binaural listeners identified the VP coordinate of the sound source more accurately than did monaural listeners, and (ii) monaural listeners identified the VP coordinate of the sound source more accurately than its HP coordinate. In part 2, it was found that foreknowledge of the HP coordinate of the sound source aided monaural listeners in identifying its VP coordinate, but the converse did not hold. In experiment 2, part 1, localization performances were evaluated when the sound originated from consecutive 45 degrees segments of the HP, with the VP segments extending from 22.5 degrees to 22.5 degrees. Part 2 consisted of measuring, on the same subjects, head-related transfer functions by means of a miniature microphone placed at the entrance of their external ear canal. From these data, the 'covert' peaks (defined and illustrated in text) of the sound spectrum were extracted. This spectral cue was advanced to explain why monaural listeners in this study as well as in other studies performed better when locating VP-positioned sounds than when locating HP-positioned sounds. It is not claimed that there is inherent advantage for localizing sound in the VP; rather, monaural localization proficiency, whether in the VP or HP, depends on the availability of covert peaks which, in turn, rests on the spatial arrangement of the sound sources. PMID- 2235292 TI - Glucose utilization, blood flow and capillary density in the ventrolateral medulla of the rat. AB - A specific population of neurons in the ventrolateral medulla (VLM) acts as the main integration center for the regulation of the sympathetic outflow to the cardiovascular system. In order to investigate whether this nucleus can be distinguished from its surroundings in the reticular formation of the medulla with respect to functional and morphological variables, the present study investigates several of such variables in this area on a quantitative basis. Local medullary glucose utilization was measured by the 2-[14C]deoxyglucose method; local medullary blood flow was quantified using iodo[14C]-antipyrine, and the local density of perfused capillaries was calculated by counting the number of intravascular fluorescent spots in brain sections after i.v. infusion of a globulin-coupled fluorescent dye. The values obtained from the VLM were compared with the respective values found in a reference area of the same brain section (gigantocellular nucleus). The values for glucose utilization, blood flow and capillary density were significantly (P less than 0.05) higher in the VLM than in the reference area (gigantocellular nucleus). This difference was 44.7% for glucose utilization, 34.1% for blood flow and 19.7% for capillary density. These data support the hypothesis that neurons in the VLM are specifically well supplied for being directly regulated in their activity by the PCO2 and pH in the arterial blood. PMID- 2235293 TI - Dependence of intracellular free calcium and tension on membrane potential and intracellular pH in single crayfish muscle fibres. AB - The dependence of intracellular free calcium ([Ca2+]i) and tension on membrane potential and intracellular pH (pHi) was studied in single isolated fibres of the crayfish claw-opener muscle using ion-selective microelectrodes. Tension (T) was quantified as a percentage of the maximum force, or as force per cross-sectional area (N/cm2). In resting fibres, pHi had a mean value of 7.06. Contractions evoked by an increase extracellular potassium [( K+]0) produced a fall in pHi of 0.01-0.05 units. The lowest measured levels of resting [Ca2+]i corresponded to a pCai (= -log [Ca2+]i) of 6.8. Intracellular Ca2+ transients recorded during K(+) induced contractions did not reveal any distinct threshold for force development. Both the resting [Ca2+]i and resting tension were decreased by an intracellular alkalosis and increased by an acidosis. The sensitivity of resting tension to a change in pHi (quantified as -dT/dpHi) showed a progressive increase during a fall in pHi within the range examined (pHi 6.2-7.5). The pHi/[Ca2+]i and pHi/tension relationships were monotonic throughout the multiphasic pHi change caused by NH4Cl. A fall of 0.5-0.6 units in pHi did not produce a detectable shift in the pCai/tension relationship at low levels of force development. The results indicate that resting [Ca2+]i is slightly higher than the level required for contractile activation. They also show that the dependence of tension on pHi in crayfish muscle fibres is attributable to a direct H+ and Ca2+ interaction at the level of Ca2+ sequestration and/or transport. Finally, the results suggest that in situ, the effect of pH on the Ca2+ sensitivity of the myofibrillar system is not as large as could be expected on the basis of previous work on skinned crustacean muscle fibres. PMID- 2235294 TI - Madin-Darby canine kidney cells. I. Aldosterone-induced domes and their evaluation as a model system. AB - Vectorial transport of salt and water in the Madin-Darby canine kidney (MDCK) cell line is indicated by the formation of domes when a monolayer is grown on an impermeable support. We investigated aldosterone-induced dome formation and evaluated the dome as an experimental model. Transepithelial dome resistance was about 80 omega cm2 and constant when dome size exceeded 2.10(-4) cm2. The relative ion conductances (expressed as transference numbers) across the dome epithelium were tNa:tCl:tk = 0.64:0.24:0.06. They reflect the permeability properties of the paracellular shunt pathway tested at physiological concentrations of the individual ions. Aldosterone accelerated dome formation in serum-deprived MDCK monolayers. Prostaglandin E1 and transferrin were supportive but not essential for aldosterone-induced dome formation. After 72 h dome density was equal in monolayers cultured in serum-supplemented medium either in the presence or absence of mineralocorticoids. We conclude that aldosterone induces cell polarization in MDCK monolayers, leading to the formation of domes. The dome epithelium appears to be electrically isolated from the adjacent monolayer and can be studied by microelectrode techniques. PMID- 2235295 TI - Autoregulation of the glomerular filtration rate and the single-nephron glomerular filtration rate despite inhibition of tubuloglomerular feedback in rats chronically volume-expanded by deoxycorticosterone acetate. AB - Tubuloglomerular feedback (TGF) function and autoregulation (renal blood flow RBF; glomerular filtration rate, GFR; single-nephron glomerular filtration rate, SNGFR) were examined in rats chronically treated with deoxycorticosterone acetate (DOCA) and given isotonic saline to drink. DOCA treatment depressed arterial plasma renin activity, expanded plasma volume by 25% and increased arterial blood pressure. Autoregulation of RBF and GFR was maintained in the DOCA animals above 90 mm Hg and 110 mm Hg respectively, whereby both GFR and RBF were lower than in controls. Micropuncture experiments demonstrated the absence of TGF in the DOCA animals. There was no difference between SNGFR values measured in the distal and proximal tubules, nor was there a significant response of SNGFR when loops of Henle were perfused with Ringer's solution at 20 nl/min. Loop perfusion in control rats with tubular fluid collected in DOCA rats elicited a normal TGF response, showing that TGF inhibition in the DOCA animals is due to changes in the function of the juxtaglomerular apparatus. In contrast to control rats, proximal SNGFR was perfectly autoregulated. These results suggest that TGF is not primarily responsible for autoregulation and that the vasodilatation normally resulting from acute TGF interruption is therefore compensated by some other mechanism such that RBF and GFR are lower than in controls. PMID- 2235296 TI - Cholinergic agonists increase cell calcium in rat medullary collecting tubules. A fura-2 study. AB - The intracellular free calcium concentration [Ca2+]i of rat medullary collecting tubules was calculated from microscope fluorescence measurements in single pieces of fura-2-loaded tubules superfused at 37 degrees C. When carbachol (10(-4)-10( 3) M) was added in the superfusate, a biphasic increase in [Ca2+]i was generally obtained, which included an early peak phase and a sustained plateau thereafter; sometimes, the peak phase was not apparent; the plateau was maintained as long as the agonist was applied. Several responses could be induced successively without a fall in responsiveness. From dose/response curves, K1/2 values of about 10(-5) M for carbachol and 10(-6) M for acetylcholine were obtained. The effects of the agonists were suppressed with 10(-4) M of atropine or pirenzepine, indicating the presence of muscarinic receptors of the M1 type. In the absence of external calcium, the peak phase of the response was preserved while the plateau phase was suppressed; thus, the peak involves the release of calcium stored in organelles, whereas the plateau involves the entry of external calcium through calcium channels which were voltage independent and insensitive to the usual calcium blockers. PMID- 2235297 TI - Role of voltage- and Ca2(+)-dependent K+ channels in the control of glucose induced electrical activity in pancreatic B-cells. AB - Low concentrations of tetraethylammonium chloride (TEA), which inhibit voltage- and Ca2(+)-sensitive K+ channels (K(+)-VCa channels), were used to investigate whether these channels play a role in the control of glucose-induced electrical activity (slow waves with spikes) in mouse pancreatic B-cells. Addition of 2 mM TEA to a medium containing 0, 3 or 6 mM glucose had no effect on the membrane potential of B-cells or on 86Rb+ efflux and insulin release from isolated islets. In 10 mM glucose, 0.5-2 mM TEA produced a concentration-dependent increase in spike amplitude without modifying slow-wave duration or frequency. Insulin release was only slightly increased under these conditions. In conclusion, K(+) VCa channels are not operative when the B-cell membrane is not depolarized (in low glucose). They appear to play a role in the repolarization of the spikes but not in that of the slow waves. In contrast to ATP-sensitive K+ channels, K(+)-VCa channels are not a target on which glucose acts to regulate electrical activity in B-cells and, hence, insulin release. PMID- 2235299 TI - Phrenic nerve responses to lung inflation and hypercapnia in decerebrate dogs. AB - The effects of changes in static airway pressure (Paw) and arterial PCO2 (PaCO2) on phrenic nerve activity were studied in unanesthetized, decerebrate dogs and compared with previous results from chloralose/urethane anesthetized dogs using the same experimental preparation (Mitchell et al. 1982; Mitchell and Selby 1987). In ten mid-collicular decerebrate dogs, the lungs were independently ventilated while the left pulmonary artery was occluded and the right vagus nerve was transected. Changes in left lung Paw, therefore, exerted effects on pulmonary stretch receptors without altering blood gases; changes in the inspired gas ventilating the right lung controlled blood gas composition, without altering lung volume feedback. Phrenic burst frequency (f) and integrated amplitude (Phr) were monitored while Paw was varied between 2 and 12 cmH2O at various constant levels of PaCO2 between 31 and 69 mmHg. The major findings of this study are: (1) hypercapnia decreases the slope of the relationship between expiratory duration (tE) and Paw in both decerebrated and anesthetized dogs; (2) hypercapnia increases the inspiratory duration (tI) in decerebrated, but not anesthetized dogs; and (3) hypercapnia decreases the slope of the relationship between f and Paw due to these effects on tE and tI. These results support previous studies indicating that vagal and suprapontine mechanisms exert independent effects on respiratory timing. It is concluded that neither suprapontine influences nor anesthesia are necessary in the mechanism underlying interactions between stretch receptors and CO2-chemoreceptors in modulating tE. Furthermore, decerebration reveals a unique effect of CO2-chemoreceptors on tI, an effect found in anesthetized dogs only after carotid denervation. PMID- 2235300 TI - Long term comparison of some shock attenuating insoles. AB - The effect of one years general use on the performance of four shock attenuating insoles is reported. Testing was carried out using the JP Biomechanics Shock Meter on twelve volunteers on a timed oval course at eight intervals during the year. The results show that two of the insoles perform well (Viscolas and PPT) although deterioration does occur after 6-9 months use; the other two insoles (Plastazote and Gait Aid) perform poorly. It is suggested that manufacturers provide some information to the user or supplier regarding the effective life of their products. PMID- 2235298 TI - Aldosterone low-dose, short-term action in adrenalectomized glucocorticoid substituted rats: Na, K, Cl, HCO3, osmolyte, and water transport in proximal and rectal colon. AB - The short-term action of aldosterone in physiological concentration on net fluxes of Na, K, Cl, HCO3, osmolytes, and water was examined in the proximal colon and rectal colon of adrenalectomized (ADX) rats in vivo. The measuring time was 12 h, divided in eight periods of 90 min. (a) Aldosterone alone (6 nmol h-1 kg-1) did not stimulate transport in ADX rats. In these experiments plasma [K] increased to fatal values. A basal glucocorticoid substitution of 24 nmol h-1 kg-1 corticosterone caused plasma K to stay constant throughout the experiment, so that epithelial transport was not handicapped by non-specific effects of ADX, but this also did not restore the decreased transport of ADX rats to control values. Under these conditions (absence of aldosterone) in the rectal colon Na and H2O transport was zero, whereas in the proximal colon flux rates were depressed by between 30% and 50%. In contrast, basal glucocorticoid substitution of 18 nmol h 1 kg-1 corticosterone plus infusion of 6 nmol h-1 kg-1 aldosterone caused transport stimulation to values not significantly different from those of non-ADX controls. We conclude that after ADX, aldosterone at physiological concentrations increases transport if, as a prerequisite, a basal glucocorticoid substitution is provided. Transport of Na, K, and H2O is under the total control of aldosterone in the rectal colon but is only moderately altered in the proximal colon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235301 TI - Accelerations due to impact at heel strike using below-knee prosthesis. AB - The acceleration in the sagittal plane of the prosthetic tube at heel strike in normal walking was measured in five healthy amputees with their definitive below knee prosthesis, every subject using six different prosthetic feet, wearing sport shoes as well as leather shoes. The experiments were carried out in the rehabilitation centre "Het Roessingh", Enschede, The Netherlands. Maximum accelerations were extracted from the acceleration-time-signal. Mean acceleration maxima of all subjects were calculated for each foot-shoe combination to eliminate the individual influence of the subjects. In the axial direction the maximal accelerations demonstrate a clear difference among the prosthetic feet and the shoes, while in dorsoventral (tangential) direction the inter-individual variation in the acceleration extremes dominates the difference between the types of footwear. In comparison with non-amputees the magnitude of the maximal axial acceleration at heel strike does not differ significantly. PMID- 2235302 TI - An audit of amputation levels in patients referred for prosthetic rehabilitation. AB - Most lower limb amputations in the United Kingdom (UK) are carried out within general surgical, orthopaedic and plastic surgical units of district hospitals. This study of patients referred for rehabilitation was undertaken to determine the number and specialty interests of surgeons referring amputees, the numbers referred by each and, as one of several possible measures of appropriateness for rehabilitation, the amputation levels in patients referred for the first time to one sub-regional Disablement Services (limb fitting) Centre (DSC) over a 14 month period. Thirty nine surgeons, referred 263 amputees. The majority (61%) of surgeons referred 5 or fewer: a nucleus of 11 vascular surgeons (28%) referred 64% of the patients. The underlying pathology, specialty interest of the surgeon or numbers referred by individual surgeons had no relation to final healed level which was below the knee in 55% of cases compared to national figures for all other DSC's ranging between 39% and 48% below-knee between 1981 and 1988. Since current practice in the UK is to refer all but the frailest patients for consideration of prosthetic rehabilitation, this study suggests that, nationally, more patients could be suited for the functionally superior below-knee level of amputation than are currently benefiting from it. PMID- 2235303 TI - A survey of amputations at Dodoma Regional Hospital, Tanzania. AB - A survey of 143 amputations performed at Dodoma Regional Hospital, Tanzania between 1983 and 1988 is presented. Consideration is given to indications for amputation, amputation levels, stump revision and supply of prostheses. PMID- 2235304 TI - Prosthetic use and functional and social outcome following major lower limb amputation. AB - A total of 175 consecutive below and above-knee amputees sent to the prosthetic workshop in Helsinki for prosthetic fitting from 32 hospitals were reviewed to determine their functional ambulation and social adaptation. The average age of the patients was 62.2 years at the time of the prosthetic fitting. The mortality was 11% (19) during the first postoperative year. One-year postoperative information was obtained for 141 of the surviving patients (90%) by personal contact. At the time of the review, 68% of the amputees (96 patients) who had been fitted with a prosthesis made extensive and regular use of it. Half of all the above-knee amputees and 79% of the below-knee amputees used their prosthesis throughout the day or over seven hours a day. A total of 72% of the above-knee amputees (33/46) and 85% of the below-knee amputees (67/79) had useful ambulation, at least indoors. Of the 141 patients contacted, 124 (88%) lived in their own homes. The remaining 16 patients (11%) lived in apartment houses for the aged or old people's homes. A total of 48 amputees (34%) needed a regular home help. PMID- 2235305 TI - Gait recovery pattern of unilateral lower limb amputees during rehabilitation. AB - The aim of this study was to determine the rate at which gait recovery as measured by temporal distance factors (velocity and symmetry) occurs in unilateral lower limb amputees. A microcomputer foot switch system was used to record the gait patterns of twenty subjects, mean age 65.1 years. The initial measurement was taken when the subject was capable of walking 6 metres with an interim prosthesis within the parallel bars. The patient sample as a whole was analyzed and subjects were further divided into four groups, depending on ambulatory aid required at discharge. Group A, n = 3 used no aid, Group B, n = 5 used a single stick, Group C, n = 6 used 2 single sticks and Group D, n = 5 required frames. A one way analysis of variance (F = 4.55, p = 0.02) showed a significant difference between the Groups, (A and D, B and D, C and D). The major velocity increase occurs within the first 30 days of the gait training programme. Overall about 55% increase in velocity can be expected within the first fifteen day period followed by an additional 30% between days 15-30. A moderately strong correlation (r = 0.78) was found between initial and discharge velocity. The correlation between initial and discharge symmetry was weaker (r = 0.50). PMID- 2235306 TI - Splinting for CDH: temporary splinting for the neonate. AB - A simple method of maintaining hip abduction in the neonate with suspected congenital hip instability is described. Clinical observations and parental impressions are initially favourable. PMID- 2235307 TI - [MR imaging of compressive cervical myelopathy after surgery--high signal intensity of the spinal cord on T2 weighted images]. AB - We reviewed the MR images of 32 patients with cervical myelopathy, showing lesions of high signal intensity in the spinal cord on the sagittal T2 weighted images (T2WI) after surgery: 16 with OPLL; 9 with spondylosis; 4 with disc herniation and 3 with trauma. All images were obtained on a superconducting 1.5 Tesla system. The lesions were classified into five groups, according to the shape and grade of signal intensity on the sagittal T2WI: (I) oval-shaped lesion of signal intensity less brighter than CSF with blurred margin, (II) longitudinal linear-shaped lesion of signal intensity similar to CSF, (III) spindle-shaped lesion of signal intensity similar to CSF, (IV) round-shaped lesion of signal intensity similar to CSF and (V) mixed-types lesions which consisted of group I and II. The present study was summarized as follows: 1) Oval-shaped lesions were seen in the cases of disc herniation and spondylosis with relatively short duration of the symptom, presumptively with relatively short duration of the symptom, presumptively indicative of edema. 2) Most cases of OPLL and spondylosis showed linear-shaped lesions, suggesting necrosis and/or cavitations of the central gray matter. 3) One case of spondylosis developed a spindle-shaped lesion, implicating syringomyelia. 4) Round-shaped lesions were seen in the cases of spinal trauma, suggesting posttraumatic cyst. 5) In a case of mixed-typed lesion examined pre- and postoperatively, only an oval-shaped lesion decreased in size after surgery. PMID- 2235308 TI - [MRI of splenomegaly]. AB - Splenomegaly was evaluated by a 0.1 T MR system using multi-echo SE image. (TR = 1500 msec., TE = 40, 80 and 120 msec.) Calculated measurement of T2 relaxation time was obtained. Material consists of 32 cases including 14 liver cirrhosis, 3 chronic myelocytic leukemia, 1 malignant lymphoma and 14 normals. 1) T2 value of normal spleen measured 113.7 +/- 5.68 msec. 2) Splenomegaly due to congestion had the prolonged T2 value of 122.6 +/- 10.25 msec. 3) T2 value of splenomegaly with malignant cell infiltration such as leukemia and lymphoma were shorter than normal spleen. Good histological correlation was obtained in MRI findings of splenomegaly due to congestion and malignant cell infiltration. PMID- 2235309 TI - [Improved methods for transseptal left heart catheterization]. AB - Although the transseptal approach is useful for evaluation of reliable hemodynamics, this technique is not used commonly for its invasive procedure. We report a new technique for transseptal left heart catheterization utilizing J shaped guide wire (0.018 inch). The guide wire is available for protecting the atrial wall from perforation by transseptal needle. Transseptal approach was performed by this technique in 58 patients with aortic valvular disease and mitral stenosis, including 6 cases of percutaneous transluminal mitral commissurotomy. We conclude that the J-shaped guide wire and the new technique make transseptal approach a safe and reliable procedure for even inexperienced hands. PMID- 2235310 TI - [Liver abscess as a complication of TAE--risk factors and prevention]. AB - Transcatheter hepatic arterial embolization for not only hepatocellular carcinoma but metastatic liver cancers is nowadays prevalent. Gall bladder infarction, cholangitis, peptic ulcers, pancreatitis, and aneurysm are reported as complications of it. But the liver abscess following it is rare. We reviewed three cases of liver abscesses after transcatheter hepatic arterial embolization. Biliary tract congestion and inflammation, and iatrogenic contaminations are supposed to major factors that caused liver abscesses. We think we should refrain from the embolization until biliary tract disorders are resolved and take care not to contaminate the proceeding materials in addition to mixing antibiotics with embolus. PMID- 2235311 TI - [Self-expandable metallic stent for use in venous occlusions]. AB - Expandable metallic stent was successfully introduced to 5 patients including idiopathic obstruction of the hepatic portion of the inferior vena cava (1 case), superior vena cava obstruction from metastatic lymphnodes swelling (2 cases) and IVC obstructions from liver metastases or lymphnodes metastases (2 cases). The obstructions were 4-14 cm long in the case of venous obstructions due to lymphnodes metastases and 2 cm long in the case of idiopathic hepatic IVC obstruction. In all cases, the stents were introduced by using 12-16 Fr catheter percutaneously without any complications. The stent used was connected up to 7 pieces by using wire struts depending length of the obstructions. However the stents connected more than 5 pieces were difficult to advance through the catheter. The patients who had been treated with stents had been free from hazardous complications such as lower extremity swelling, and pain. PMID- 2235312 TI - [Evaluation of tiny abnormal mucosal findings on double contrast barium enema study]. AB - Tiny abnormal mucosal findings on double contrast barium enema studies in 104 cases were classified into 5 patterns, as follows 1) small elevation, 2) elevation with barium fleck, 3) spotty barium fleck, 4) ill defined barium fleck and 5) barium fleck with halo. Each mucosal pattern was correlated with age, sex and symptoms, as well as the coexistence of the fine network pattern. They were compared with those of 86 control cases. 44 histologically proven cases were reviewed in order to clarify the clinical significance of the above 5 patterns. Incidence of the tiny mucosal findings was 4.8% (104/2186). 1) small elevation, 2) spotty barium fleck, 3) ill defined barium fleck and 4) barium fleck with halo were suggested the possibility of inflammatory bowel diseases. PMID- 2235313 TI - [Preliminary study and clinical evaluation method of ioversol in angiocardiography--establishment of safety evaluation parameters and reliability of radiographic quality evaluation]. AB - A multi-center clinical study of a new nonionic iodinated contrast medium (ioversol) was performed in 26 patients undergoing left ventriculography (LVG) and coronary angiography (CAG) at four centers. The aims of this study were to try to establish a clinical evaluation method on contrast media in angiocardiography and to determine radiographic efficacy and safety of ioversol. The reliability of the method evaluating the radiographic quality of the contrast medium was also examined with statistical analysis. Excellent radiographic efficacy was observed with ioversol and morphological diagnosis was possible in all cases. The electrocardiograms (ST-segment deflection, T-wave amplitude, QT interval, corrected QT interval, arrhythmia and heart rate) and the hemodynamic parameters (left ventricular systolic and end diastolic pressures, left ventricular dp/dt max, aortic systolic and diastolic pressures) indicated no clinically significant changes. This study suggested that the monitoring of the ECGs and hemodynamic parameters for up to three minutes after injection of the contrast medium is sufficient for the evaluation in LVG and CAG, and that the monitoring in CAG during the first injection into each left and right coronary artery is also sufficient for the purpose. Heat sensation during injection was mild. A patient had a symptom of nausea after ioversol administration, but it was mild and transient and resolved spontaneously. There were no abnormal clinical laboratory data related to ioversol. The reliability of the radiographic quality evaluated by the individual clinical investigators was considered to be high and adaptable. However, the evaluation in the blinded cinefilms by the committee members involving all investigators would be more preferable for the higher objectivity. The study results suggest that ioversol is considered to be the efficacious and safe contrast medium for the cardiovascular angiography. PMID- 2235314 TI - [MR imaging of primary bone and soft tissue tumors]. AB - MR imaging of 131 cases with pathologically confirmed primary bone and soft tissue tumors were studied. They included 44 bone tumors (25 benign tumors, 19 malignant tumors) and 87 soft tissue tumors (55 benign tumors, 32 malignant tumors). MR imaging was performed on 0.5T, superconductive magnet system. All tumors were evaluated with T1-weighted, T2-weighted and STIR images. In some cases, contrast enhanced MR imaging with Gd-DTPA was applied. MR imaging was proving to be a valuable technique in the evaluation of patients with primary bone and soft tissue tumors. MR imaging was superior to the other modalities in delineating the extent of the tumor and their relation to surrounding structures in all cases. However, plain radiography and CT were more useful for evaluation of calcification, ossification, cortical destruction and endosteal/periosteal reaction than MR imaging. Direct sagittal and coronal images from MR imaging added accurate assessment for the relation between the tumor and their adjacent structures. MR imaging was of limited value in distinguishing benign from malignant tumors with the demonstration of tumor structures only, especially soft tissue tumors. But in bone and soft tissue tumors which have specific morphologic features and intensity patterns, MR imaging was very useful for diagnosis. PMID- 2235315 TI - [Clinical evaluation of radiotherapy for endocrine ophthalmopathy]. AB - Ten patients with severe endocrine ophthalmopathy were treated by radiotherapy at Hyogo Medical Center for Adults from May 1984 to February 1988. All but one of the patients had poorly responded to previous systemic or topical corticosteroid therapy. The target of the radiotherapy was both retrobulbar tissues. The radiation field used was about 4 x 4 cm, excluding the pituitary gland and the brain, and was angled 5 degrees posteriorly to avoid the contralateral lens. A total of 2000 cGy was given to each patient over a 2 week-period. Eight of the ten patients showed some response, with 5 of them (50%) having a good to excellent response. Treatment was more effective for soft tissue changes, proptosis and keratopathy, while myopathy was less responsive. As for the duration of the eye signs and symptoms, those of a shorter duration (less then 12 months) responded better. It was also noted that the degree of the eye muscle enlargement on the pre-treatment orbital CT scan was directly correlated to the results of the treatment. Although three of the patients experienced transient headache, there were no serious acute reactions or long term complications. In conclusion, retrobulbar radiotherapy is a well-tolerated, safe and effective treatment for severe endocrine ophthalmopathy. PMID- 2235317 TI - [Measurement of oxygen concentration in tumor cells by fluorescent probe (nitrocompound)]. AB - The hypoxic cell fraction in tumors is considered to be responsible for radioresistance. Estimating the population of the hypoxic cell fraction in tumor could develop the effective means to predict radiosensitivity. In this study, nitroacridine (fluorescent dye) was tested to estimate hypoxic status in single cells and in spheroids. The oxygen concentration in the medium was measured by oxygen electrodes utilizing polarography method, mean while that in cells was calculated from the fluorescence intensity of the dye. The fluorescent spectra from cells showed the same pattern in spite of the changed oxygen concentration in medium, on the other hand its intensity was dependent upon the oxygen concentration. Using a fixed nitroacridine concentration and a fixed staining time, oxygen concentration of cells could be determined within range from 0.1 to 1.0% values. These values are almost the same as the oxygen concentration of the radioresistant tumor cells. Thus, the fluorescent method we used in this study is considered to be useful to estimate radioresistance of tumor. However, fluorescent intensity would alter when used different cell lines, because of different cellular activity of nitroreductase. PMID- 2235316 TI - [Fever of unknown origin: re-evaluation of 67Ga scintigraphy in detecting causes of fever]. AB - Radioactive gallium citrate has been known to accumulate not only in neoplasms but also in inflammatory foci, and thus widely used to find out pyrogenic lesions in cases of unexplainable prolonged fever. However, with developments and improvements of other imaging modalities, its diagnostic significance may have changed. To probe that issue, recent 65 scans for the patients with fever of unknown origin were reviewed retrospectively. Of these, 56 had sufficient clinical assessment and laboratory examinations to evaluate causative illnesses. Gallium images of 33 patients were interpreted as positive. Local inflammatory lesions were detected in 23 cases, with lung tuberculosis, urinary tract infection, and inflammatory joint diseases as prevalent final diagnoses. Pyogenic abscesses, though popular in the literatures on fever of unknown origin, were found in only 2 cases in our present series. This seemed to be due to earlier detection of affected sites by other imaging technics. Osteomyelitis, other major cause of fever in the past, was not found this time, probably owing to wide use of antibiotics. Besides localized diseases, seven cases of generalized disorders were found. There were 3 patients with hematological malignancies, 3 with systemic autoimmune diseases, and 1 with severe infectious mononucleosis. There were three false positive cases; intestinal gallium radioactivity in 2 cases and physiological pulmonary hilar accumulation in 1 were erroneously read as abnormal. Of 23 cases with negative gallium scan, no definite cause of fever were found in 19; twelve patients had spontaneous reduction of fever, 2 did so with antibiotics, and 5 with corticosteroids. False negative cases were; two with urinary tract infection on antibiotics, one with bacterial meningitis, and one with polyarteritis nodosa. Our results reconfirmed the excellent sensitivity and accuracy of gallium scan in the diagnosis of fever of unknown origin. In addition to the detection of focal inflammations, it may sometimes contribute to an early diagnosis of unexpected systemic diseases. From the results obtained, it is advisable that, in patients with fever of unknown origin, this test should be done early in diagnostic schedule and before administration of drugs that may mask potential sites of abnormal accumulation. PMID- 2235318 TI - [Stereoscopic MR angiography of the abdomen]. AB - We have developed a new method of stereoscopic MR angiography of the abdomen using gradient echo images. Consecutive coronal scanning of the abdomen was performed by fast scan during breath hold. These images were overlapped by means of MR angiography. Then two slightly different views that can give a true stereoscopic effect were constructed. The more precise spatial relationship of the abdominal vessels can be visualized with our new method. PMID- 2235319 TI - [Usefulness of the percutaneous marking method with a coil (PMMC) for the localization of small pulmonary nodules]. AB - We surgeons have always encountered difficulty in localizing small pulmonary nodules, measuring less than 5 mm in diameter, through palpation during operation. In order to solve such a problem, we devised a new method of localizing small pulmonary nodules by applying a technique of CT-guided needle biopsy; namely, metallic spring coil is implanted through a 16 G eraster needle, the tip of which has been placed near the lesion. Our method not only secures the resection of entire lesions, but reduces an amount of lung resection through a small incision (mini-thoracotomy) as well. Furthermore, this method is also thought to be useful for open lung biopsy of pulmonary nodules, measuring less than 1 cm in diameter, in saving time and reducing an amount of lung tissue collection. In case of cystic lesion which is thought to be difficult to palpate on operation, this method can also be useful for its resection. PMID- 2235320 TI - [A short TE gradient-echo sequence using asymmetric sampling]. AB - We have developed a gradient-echo pulse sequence with a short TE less than 4 msec using a data set of asymmetric off-center sampling with a broad bandwidth. The use of such a short TE significantly reduces T2* de-phasing effect even in a two dimensional mode, and by collecting an off-center echo, motion-induced phase dispersion is also considerably decreased. High immunity of this sequence to these dephasing effects permits clear visualization of anatomical details near the skull base where large local field inhomogeneities and rapid blood flow such as in the internal carotid artery are present. PMID- 2235321 TI - [Ethanol injection for embolization of varicocele]. AB - Five patients were treated for varicocele by embolization with the use of ethanol, which has not been used before. The ethanol was injected into the spermatic vein involved in the varicocele by the technique of spermatic venography. Embolization was successful in all five patients. During the follow up period, the varicocele became smaller or disappeared in four of the five patients. In one patient, catheterization was difficult, and the effect of ethanol was unsatisfactory because of the location of its release. The varicocele appeared again 13 months after embolization. Serious side effects were not found in all patients. Embolization therapy with ethanol is easily performed and is considered to be a safe and effective method. PMID- 2235323 TI - [Computer-aided diagnosis of interstitial lung diseases]. AB - We are developing an automated method for determination of quantitative physical measures of lung textures in digital chest radiographs in order to detect and characterize interstitial lung disease. We describe a scheme of our approach for lung texture analysis, an automated classification method for distinction between normal and abnormal lungs with interstitial disease, and the effect of digital parameters on the accuracy of this computerized analysis, as well as applications of this method to the ILO pneumoconioses standard radiographs. The root-mean square (rms) variation and the first moment of the power spectrum of the lung texture were determined as quantitative texture measures based on a frequently analysis of lung textures, which represent the magnitude and coarseness (or fineness) of the lung textures, respectively. The computerized classification method is based on the analysis of these texture measures and on a data base derived from clinical cases. This classification method includes three independent tests, one for a definitely abnormal focal pattern, one for a relatively localized abnormal pattern, and one for a diffuse abnormal pattern. A comparison of receiver operating characteristic (ROC) curves obtained by radiologists and by means of the computerized classification method indicates that the computerized approach may provide performance similar to human observers in distinguishing lungs with mild interstitial disease from normal lungs. By investigating the effect of digital parameters such as pixel size, ROI size and the number of quantization levels on these texture measures obtained from the lung texture analysis and the performance of this computerized method, we attained a useful guide in the design of this computerized scheme. Texture measures obtained from computer analysis of the ILO pneumoconioses standard radiographs corresponded closely with the ILO classification categories for small opacities, though it was necessary for a qualified radiologist to identify representative areas in each ILO radiograph because of the inhomogeneous distribution of texture patterns in these standard radiographs. Our results suggest strongly that this computerized method can be a valuable aid to radiologists in their assessment of interstitial lung diseases. PMID- 2235322 TI - [Fundamental experiment of expansile force of expandable metallic stent]. AB - So far expansile force of expandable metallic stent has been estimated by only wall-distending pressure P. We estimated expansile force of stent by not only P but also a force per one unit length of wire F. F corresponds to the degree of digging into the vessel wall. P and F were thought to be useful in selecting the best stent. PMID- 2235324 TI - [Transcatheter embolization therapy of pseudoaneurysms in patients with chronic pancreatitis]. AB - Chronic pancreatitis is known to cause vascular disorders including pseudoaneurysm of peripancreatic arteries. Although the incidence of pseudoaneurysms due to pancreatitis detected by angiography has been reported as high as 10% in western literature, they are still considered rare in Japan. We reported two cases of pseudoaneurysm caused by chronic pancreatitis, one in splenic artery and the other in gastroduodenal artery, successfully treated by embolization. The embolizations were performed by occluding proximal splenic artery for splenic arterial aneurysm and gastroduodenal artery distal and proximal to the orifice for the aneurysm of gastroduodenal artery with stainless steel coils. Since the surgical therapy has high mortality rate, we consider transcatheter embolization is the treatment of choice for pseudoaneurysms caused by chronic pancreatitis. PMID- 2235326 TI - [Evaluation of axial multiplanar reconstruction CT for the diagnosis of small nodular lesions in the peripheral lung]. AB - Our study investigated the relationships between tumors and surrounding structures, particularly vessels and bronchi within lesions in the periphery of the lung. We performed axial multiplanar reconstruction CT (AMPR-CT) with a Toshiba TCT-900S scanner, as well as conventional CT (Conv. CT) and CR tomography (CR tomo.). We examined 19 patients with pulmonary lesions who later underwent surgical resection (12 with lung cancer, 1 with metastatic tumor, 1 with hamartoma, 2 with tuberculoma, and 3 with pulmonary granuloma) of a total of 43 patients with small nodular lesions less than 3 cm in diameter. AMPR-CT, Conv. CT, and CR tomo. were compared against resected specimens. The accuracy of each modality to detect involvement of bronchus, the pulmonary artery, and vein was AMPR-CT 50%:93%:91%, Conv. CT 47%:76%:55% and CR tomo. 37%:55%:42%, respectively. AMPR-CT was judged superior to both Conv. CT and CR tomo. In conclusions: 1) That AMPR-CT permits easier visualization of vessels and bronchi, and 2) That AMPR-CT is more effective than Conv. CT examinations in the morphological assessment of small nodular lesions. Thus, AMPR-CT is a useful new approach to the diagnosis of lesions in the lung. PMID- 2235325 TI - [High-field MR findings of multiple system atrophy]. AB - Magnetic resonance images obtained at 1.5T were reviewed in 23 patients with clinically diagnosed multiple system atrophy (MSA). The patient group consisted of 13 cases with olivoponto-cerebellar atrophy (OPCA), three with striatonigral degeneration (SND), and seven with Shy-Drager syndrome (SDS). In each disorder group, hypointensity of the pars compacta of the substantia nigra was frequently demonstrated as well as the atrophy of the brain stem and cerebellum. Although T2 weighted images depicted hypointensity of the putamen, which was prominent in its posterolateral part, in cases with SND and SDS, it was not encountered in cases with OPCA. Therefore, this finding was considered to facilitate differential diagnosis between OPCA and other two disorders. These hypointensities in the putamen and pars compacta of the substantia nigra may be due to excessive iron deposition and seem to correlate with extrapyramidal tract signs of MSA. PMID- 2235327 TI - [Right anterior caudo-cranial oblique (RACCO) view of portal branches]. AB - The right caudocranial oblique (RACCO) view which is obtained by tilting the image intensifier 25 degrees caudally and 30 degrees to the right while the patients lie in supine position is proposed for improved depiction of the portal venous system. Transarterial portography with digital subtraction angiography was performed in the RACCO and posteroanterior (PA) views in 32 patients. Comparison of the two views revealed that the RACCO view was superior to the PA view of the left main branch in 25 patients (78%) and of the right posterior lobe branch in 24 (75%) patients. Visibility of more distal portal branches, however, did not always improve by RACCO view. RACCO view will be useful for the evaluation of portal systems of primary and secondary hepatic neoplasms as a special view following portogram in PA projection when more detailed information is necessary on proximal portal branches. PMID- 2235328 TI - [Preliminary study of pelvic CT with air enema]. AB - In pelvic CT, several techniques (appropriate preparations) have been reported for the optimal diagnostic imagings. We demonstrated the usefulness and limitations of "Air Enema", which is one of preparations for hollow viscera in pelvic CT examination. From Oct. 1986 to Mar. 1987, 38 patients with gynecological abnormalities were evaluated by consecutive pre and post "Air Enema" CT. The patients aged 26-75 years with mean of 44.6 years. All patients were examined in prone position with 100 ml of 2% iopamidol in the urinary bladder and medical tampon in the vagina. Two consecutive scans were performed from the level of pubic symphysis to the 5th lumbar vertebra at 10 mm-15 mm intervals. The first scan was pre "Air Enema" CT, in which the rectum, entire colon and terminal ileum were not distended. The second scan was post "Air Enema" CT, in which the hollow viscera was distended by 1000 ml-1500 ml of air. Two images, each from pre and post "Air Enema" CT were evaluated on the efficacy for imaging diagnosis. In "Air Enema" CT, main useful effect was "replacement effect", which was that intrapelvic masses and/or intrapelvic paravascular spaces were clearly delineated by distended bowels. Detection and location of intrapelvic masses were correctly diagnosed when the masses were relatively small (5.3 cm in average diameter), but there were no advantages in cases in which the pelvic masses were large enough to occupy the pelvic cavity (12.7 cm in average diameter). Abdominal pain was the most common adverse reaction to this technique. But complaints usually disappeared in few hours after examination. Thus, "Air Enema" seems to be useful preparation for pelvic CT examination to detect relatively small intrapelvic masses and abnormalities. PMID- 2235329 TI - [Treatment results of maxillary sinus carcinoma. A retrospective study]. AB - The treatment results of a total of 617 cases with maxillary sinus carcinoma mainly treated by radiotherapy at the Department of Radiology, Osaka University Hospital between 1967 and 1983 were reviewed. The overall actuarial 5-year survival rate was 36.2%. The cases were divided into 3 groups by period of the treatment modalities corresponding each 5-year survival rate of 24.1% on 217 patients for 1967 to 1971, 40.0% on 155 patients for 1972 to 1975, and 44.6% on 245 patients for 1976 to 1983. The treatment results have improved in 5-year survival rate as modifying treatment modality. The actuarial 5-year local control rate was 60.0% for T1 on 9 patients, 43.1% for T2 on 181 patients, 31.7% for T3 on 246 patients, and 19.2% for T4 on 181 patients, respectively. For more detailed analysis of the results, the cases were divided into 4 groups according to the initial treatment; the group 1 was treated by radiotherapy alone (RT), the group 2 by radiotherapy combined with intra-arterial infusion of 5-fluorouracil (RT + 5-FU), the group 3 by radiotherapy combined with surgical removal of the tumor mass through curettage under the general anesthesia (RT + OP) and the group 4 by multidisciplinary procedure combined with radiotherapy, 5-FU regional infusion and curettage (RT + 5-FU + OP). In the T2 cases, the 5-year actuarial local control rate was 25.5% for RT on 51 patients, 45.0% for RT + 5-FU on 55 patients, 58.2% for RT + OP on 23 patients and 51.5% for RT + 5-FU + OP on 52 patients, respectively. In the T3 cases, the rate was 13.2% for RT on 85 patients, 33.6% for RT + 5-FU on 78 patients, 52.3% for RT + OP on 31 patients and 45.9% for RT + 5-FU + OP on 52 patients, respectively. In the T4 cases, the rate was 7.6% for RT on 77 patients, 27.2% for RT + 5-FU on 52 patients, 17.8% for RT + OP on 20 patients and 31.5% for RT + 5-FU + OP on 32 patients, respectively. The combination therapy with 5-FU regional infusion and/or curettage had successfully improved the local control rate. On the T2 and T3 cases of RT + OP, an additive effect of 5-FU infusion was not significant, and also on the T4 cases of RT + 5-FU, any usefulness of curettage could not be found.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2235330 TI - [Differential diagnosis between nonhyperfunctioning adenoma and adrenal metastasis on adrenocortical scintigraphy]. AB - Adrenocortical scintigraphy using I-131-adosterol was performed in six cases of nonhyperfunctioning adenoma incidentally discovered on CT scans and four cases of adrenal metastasis. In all six cases of nonhyperfunctioning adenoma, there was increased uptake of of the I-131-adosterol on the side of the adrenal mass discovered at CT. In three of four cases of adrenal metastasis, there was no uptake of the I-131-adosterol on the side of the mass detected at CT. Uptake was symmetrical in one case of adrenal metastasis. Adrenocortical scintigraphy is able to differentiate nonhyperfunctioning adenoma from adrenal metastasis in recognition of increased uptake of I-131-adosterol on the side of the adrenal mass discovered on CT scans. PMID- 2235331 TI - [Scrotal scintigraphy in the diagnosis and grading of varicocele]. AB - Scrotal scintigraphy with 99mTc-red blood cells has been reported as a useful method for detecting varicocele. In this study we analysed the scintigraphy of 251 infertile males with clinically diagnosed or suspected varicocele, in an attempt to establish a grading system of varicocele. Scintigraphically varicocele was diagnosed in 207 patients on the basis of pooling in hemiscrotum in static images and/or early flow through the spermatic cord vessels in dynamic images; physical examination overlooked 17 of them. Of the 207 patients, all had pooling (153 left-sided, 1 right-sided, and 53 bilateral pooling) and 52 had early flow. The early flow was a less sensitive sign for varicocele than the pooling and invariably accompanied by the intense pooling. The early flow may be related to increased shunt flow through varicocele. According to the scintigraphic findings, varicocele was classified as follows: Grade I (small varicocele with faint early flow or mild localized pooling, n = 103), Grade II (medium varicocele with obvious early flow or curvilinear mottled pooling, n = 67) and Grade III (large varicocele with marked early flow or pooling, n = 37). Clinical assessment (93 small, 68 medium, and 54 large varicocele) supported the scintigraphic classification. Scrotal scintigraphy, therefore, facilitates precise evaluation of varicocele based on its morphology and hemodynamics. PMID- 2235332 TI - [Scrotal scintigraphy in varicocele compared with physical examination and venography]. AB - Scrotal scintigraphy using a gamma-camera and 740 MBq of 99mTc-labeled human serum albumin was performed on 43 patients with suspected varicocele. In 39 patients (37 left-sided, 2 bilateral) with proven varicoceles, sensitivities by the static and dynamic images were 92.3% and 51.3%, respectively. There were no false positive cases in either image (4 cases with no varicocele). It has been suggested that static images are useful for the detection of varicocele in infertile men. A comparison between the static and clinical grades showed that the static grades appeared to become higher in proportion to the clinical grades. A comparison between the static grades and the diameter of the internal spermatic vein (ISV) showed that the mean value of the diameter of the ISV in SG 1, SG 2 and SG 3 was 4.1 +/- 0.66 mm, 5.1 +/- 0.68 mm, and 6.2 +/- 0.79 mm, respectively. Patients with higher static grades had ISVs of significantly larger diameter (SG 1 vs SG 2; p less than 0.05, SG2 vs SG3; p less than 0.01, SG 1 vs SG 3; p less than 0.01, t-test). A comparison between the dynamic images and the degree of reflux in the ISV showed that patients with positive dynamic images had a significantly greater degree of reflux (p less than 0.01, Chi-square test). From these observations, scintigraphic findings would reflect the degree of reflux in the ISV, the diameter of ISV, and the size of the varicocele. Furthermore, from the remarkable changes between pre- and post-therapeutic findings on the scintigrams, therapeutic effects could be easily and objectively assessed by scintigraphy. PMID- 2235333 TI - [Determination of the point position from two orthogonal X-ray photographs using least squares method and geometrical solutions]. AB - Six sets of solutions for calculating the position of an interest point were obtained geometrically using four measured image coordinates on two X-ray photographs orthogonally projected. When the image coordinates had no error, all the solutions gave the same position without error. When an error occurred, the calculated positions differed from each other due to the propagation of error. Some solutions could not be used for this determination owing to a large propagation of error. Under conditions similar to those of clinical practice, the ratio of maximum error of position calculated by the six geometrical solutions to minimum error was about 426. The least squares method that we proposed gave results with less error. When one of the image coordinates could not be measured for some reason, the least squares method became automatically equivalent to one of the six geometrical solutions. PMID- 2235334 TI - [Trial for improvement of image quality of chest tomography with computed radiography]. AB - In conventional X-ray tomography, the presence of blurring which is caused by the object outside the focal plane reduces the image quality of the focal plane. With the application of computed radiography for the conventional chest tomography, two kinds of image processing techniques for the elimination of the blurring were examined. As a result, each image processing technique fairly succeeded in improving the image quality. PMID- 2235335 TI - [Clinical usefulness of 67Ga-citrate scintigraphy combined early image in malignant lymphoma--detection of abdominal lesions]. AB - In order to improve the diagnostic accuracy in detecting abdominal lesions of malignant lymphoma, we studied prospectively the usefulness of 67Ga-citrate scintigraphy combined 5 to 6-hour early image with conventional 72-hour delayed image after injection. During the period from July 1986 to September 1988, total 41 67Ga-citrate scintigrams performed on 28 patients with malignant lymphoma (3 Hodgkin's disease, 25 non-Hodgkin lymphoma) were evaluated between early and delayed image regarding to such points as follows; 1) the physiologic bowel uptake of 67Ga-citrate, 2) detection of abdominal lesions indicated by other diagnostic modalities involving computed tomography, lymphography and ultrasonography. Following results were obtained: 1) Prominent bowel uptake of 67Ga-citrate thought to be difficult to interpret the scintigram was observed in only 1 of 41 (2%) on early image versus 13 of 41 (32%) on delayed image. 2) Known lesion sites were detected in 24 of 31 (77%) on early image versus 21 of 31 (68%) on delayed image, resulting in 26 of 31 (84%) in combination with both images. 3) There were 2 false-positive and 5 false-negative lesions. Two false-positive lesions on early image were explained by physiologic hepatic uptake with ill defined outline and bladder uptake. On the other hand, all of 5 lesions on delayed image were explained by prominent bowel uptake. 4) Two patients were revealed higher splenic uptake comparing with hepatic uptake on both images, later proved to be diffuse splenic involvement without evidence of lesions on other diagnostic modalities. 5) The lesions less than 2 cm in diameter could not be detected in both images.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235336 TI - [Late adverse reactions of non-ionic intravenous contrast media]. AB - A prospective study of late adverse reactions of non-ionic intravenous contrast media was performed. Information was collected from questionnaires returned by the patients, and also from further interviews. The incidence of adverse reactions was 8.3% in all patients, and was higher in female (11.1%) than male (5.8%). They were more frequent in the patients with age ranging from 20 to 49 than those older than 50. The most frequent symptom was headache, followed by itching, skin rashes, nausea, dizziness, and general fatigue. More than half of the reactions occurred within six hours after injection, but reactions a few days later were also reported. PMID- 2235337 TI - [Use of radiolabeled monoclonal antibodies for diagnostic imaging]. AB - Monoclonal antibodies (MoAbs) are expected to carry radionuclides selectively to target tissues and to offer antigen-specific diagnosis. Indium (In)-111 has many favorable nuclear properties and is efficiently labeled with MoAbs using DTPA as a bifunctional chelating agent. In-111 labeled MoAbs are clinically employed for the diagnosis of malignant melanoma, colorectal cancer and acute myocardial infarction in Japan. Although non-specific deposit of In-111 was seen in liver and bone-marrow, scintigraphy using In-111 labeled MoAbs was encouraging, since it detected about 80% of tumors, tumors missed by conventional diagnostic methods such as CT, and tumors in patients with normal serum CEA values, and acute myocarditis as well as acute myocardial infarction was positive with In-11 labeled Fab fraction of anti-myosin Ab. Acute or subacute toxicity was not observed. Human anti-murine antibody (HAMA) was detected in 53 of 64 (82.8%) patients who were intravenously administered with 20 to 42 mg of anti-melanoma or anti-CEA MoAbs (whole IgG). In contrast, only 5 of 406 (1.2%) patients had detectable levels of HAMA in their serum after receiving 0.5 mg of Fab fraction of MoAb. Recently mouse-human chimeric Ab has been produced by recombinant DNA techniques, which localized well in xenografted tumors and seems to be promising for clinical use. Investigations are under way to increase the tumor to non-tumor ratio by modifying chelating agents for coupling MoAbs with radionuclides. PMID- 2235338 TI - [Effects of sampling bandwidth in MR imaging]. AB - Phantom and volunteer study was performed with spin-echo sequences of different sampling bandwidths to evaluate the narrow bandwidth signal acquisition technique. Our results demonstrated the characteristics of the narrow bandwidth sequence as follows: SNR improvement, sensitive to the field inhomogeneity and motion, loss of edge definition for short T2 tissues, and prominent chemical shift artifacts. Narrow bandwidth sequence with flow compensation was suitable for brain T2 weighted images because of its high SNR and less artifacts. In spite of the improvement of SNR, the narrow bandwidth technique may be inappropriate for short T2 tissues such as muscle, because of prominent chemical shift artifacts and loss of edge definition. Consequently, sampling bandwidth is one of the parameters which can be manipulated to improve MR image quality. PMID- 2235339 TI - [Analysis of cervical metastatic lymphadenopathy by ultrasonography]. AB - One hundred and eight cervical lymph nodes of 37 patients were evaluated by ultrasonography. All lymph nodes were examined histologically, and among them 63 lymph nodes were metastatic nodes. If submandibular, submental, mid and inferior internal jugular lymph nodes larger than 8 mm, and superior internal jugular lymph nodes larger than 9 mm had been regarded as metastasis, high sensitivity (92%) was demonstrated. All of 31 lymph nodes with unclear or irregular margin were metastatic. Eccentric hyperechoic area, which was considered to be the hilus of the lymph node, was observed in 20 nodes. Those were non-metastatic lymph nodes. Otherwise, all of 48 lymph nodes with inhomogeneous internal echoes or with central hyperechoic area and peripheral hypoechoic zone were metastatic. The in vivo and in vitro ultrasonograms of 25 lymph nodes were compared with histopathological findings. The metastatic region was not differentiated with the remaining area of the lymph node by ultrasonography. Necrosis showed an-, hypo-, iso-, or hyperechoic. Fibrosis showed iso- or hyperechoic. Inhomogeneous internal echoes were proved to be necrosis and fibrosis, and such a lymph node was metastatic. The eccentric hyperechoic area of the non-metastatic lymph node was attributed to fatty tissue. Ultrasonography was a useful examination for evaluating cervical lymph nodes. PMID- 2235340 TI - [Ewing sarcoma: changes after radiation and chemotherapy]. AB - We retrospectively studied 52 cases of Ewing sarcoma to elucidate the pattern of healing and/or recurrence after radiation and chemotherapy. Persistent soft tissue mass was a sign of failure to respond to therapy. Repair or healing of lytic or blastic bone changes were slow and often minimal, and usually bone changes became gradually stable over 3 years. After bone changes became stable, localized new bone changes represented recurrence or secondary malignant neoplasms. PMID- 2235341 TI - [MR imaging of intracerebral hematomas: sequential changes of signal intensities on a 0.2T permanent magnetic system]. AB - We performed 67 examinations in 27 patients with intracerebral hemorrhage on a 0.2T permanent magnet system. MR appearance of the hematomas on T-1 weighted and T-2 weighted images (T1WIs, T2WIs) was carefully evaluated according to the chronological course of the lesions after the ictus. The signal intensity of each hematoma was classified into four stages in terms of the degradation process of hemoglobin. Four hematomas examined within 24 hours after the ictus (ultra-acute stage) appeared slightly hypointense or isointense relative to the normal brain tissue on T1WIs and markedly hyperintense on T2WIs. Three of those lesions became partially or totally hypointense on T2WIs at the acute stage (one to three days after the ictus), though all appeared in general isointense on T1WIs. The hematomas at the subacute stage (four days to two weeks after the ictus) were hyperintense on both T1WIs and T2WIs. At the chronic stage (more than two weeks after the ictus) the signal pattern of hematomas became variable: hyperintense on both T1WIs and T2WIs early at this stage; hypointense on T1WIs but mostly hyperintense on T2WIs latter. The results indicate the clinical feasibility of a low tesla system for MR evaluation of intracerebral hematomas. PMID- 2235342 TI - [MR imaging of mucocutaneous malignant melanoma in the head and neck]. AB - MR imaging was performed in three patients with mucocutaneous malignant melanoma of the head and neck, and surgical specimens were investigated in MR-pathological correlation. Two of 3 cases were revealed to be melanotic melanoma; one arose in the maxillary sinus, and another in the bulbar conjunctiva. The remaining case was amelanotic melanoma originating in the nasal cavity. Two cases of melanotic melanoma showed different intensity on T1WI according to the melanin concentration; the more the melanin-producing process existed, the higher intensity in the tumor was shown. On T2WI there were also some differences in signal intensity; the case having more concentration of melanin changed lower partially in the areas where very high intensity was noted on T1WI, while another case remained unchanged. These findings are based on the inherent paramagnetic effect mostly compatible with the previous reports. On the other hand, the amelanotic melanoma was demonstrated as an intermediate intensity both on T1- and T2WI. Because of the higher incidence of hemorrhage in/around the tumor, it is an important diagnostic clue to this tumor, as in our case of amelanotic type. On reviewing the three cases, we consider that MR imaging offers a useful adjunct in the diagnosis of malignant melanoma. PMID- 2235343 TI - [The MR findings on the corpus callosum of normal young volunteers]. AB - The size and shape of the corpus callosum of twenty-seven normal young volunteers (age 18-31 years, 17 men and 10 women) were investigated using a superconducting high field (1.5 T) MRI unit. The length of the corpus callosum was 71.1 +/- 5.1 mm (mean +/- S.D.) and the height was 24.9 +/- 2.1 mm. The length ratio of the corpus callosum to the brain was 43.9 +/- 2.3% with the ratio of the height 25.0 +/- 2.3%. The callosal index (height/length) was 35.4 +/- 2.9%. The area of the corpus callosum in the midsagittal plane was 681.4 +/- 93.6 mm2 (min. 563 mm2 to max. 902 mm2). We divided the corpus callosum into three segments: rostrum and genu; anterior and posterior trunks; splenium. Each part accounts for one third of the total area of the corpus callosum. The genu and splenium were generally equal in thickness. The minimal thickness of the trunk was 3 mm with the maximal one 9 mm. The posterior trunk was never thicker than the anterior one. The posterior part of the posterior trunk showed thinning and concavity in almost all cases. So-called impressio corporis callosi was observed in 12 cases (44.4%). Thirteen cases (48.1%) showed a shallow concave configuration at the anterior dorsal surface of the corpus callosum. Six cases of these were thought to be due to compression by the pericallosal artery. This finding was not detected in the posterior portion of the corpus callosum. This concavity was also seen in infants. The thinning of the posterior part of the posterior trunk was seen after the development of the splenium, but the concave configuration at the anterior dorsal surface of the corpus callosum may be encountered before the full development of the genu and splenium. PMID- 2235344 TI - [MRI diagnosis of the lung nodule--experimental and clinical studies regarding environmental effects on relaxation time measurement]. AB - There have been several reports on MRI concerning the differential diagnosis of lung nodules by the measurement of relaxation time. Measuring the relaxation time has been reported to be of little value because of a lack of reliability in differentiating nodules, and may vary according to environmental effects such as tumor size, location and physical constitution as seen on CT. From this point of view, we have newly devised a phantom of the thorax containing simulated lung nodules in order to evaluate the environmental effects on the relaxation time, and investigated the fluctuation of the T1 and T2 values of lung nodules of the phantom. The experimental study using simulated lung nodules revealed that T1 and T2 values of the lung nodules shift according to various environmental factors such as tumor size, location, and blood flow. It is concluded that there are definite environmental effects on MRI measurements as seen on CT. In clinical studies with patients showing nodular shadows on chest radiography, we calculated the T1 and T2 relaxation times of lung nodules pre- and post-operatively. The T1 and T2 relaxation times of resected tumors were measured approximately 2 hours after surgery. There was a tendency for the T1 values to decrease and T2 values to increase when compared to preoperative conditions. However it could not be proved that the changes of the relaxation times were solely due to environmental effects, because there were lots of valid causes which affect remained such as loss of blood flow and tissue degeneration after surgery. PMID- 2235345 TI - [Clinical efficacy of Z-100 for the treatment of leukopenia caused by radiotherapy--a multi-center double-blind comparative study with inosine]. AB - The clinical usefulness and the optimal dose of Z-100 for the treatment of leukopenia caused by radiotherapy for malignant tumors was evaluated in a double blind study comparing 20 micrograms and 30 micrograms injections of Z-100 and inosine (Z-20, Z-30 and IN group, respectively). The effective rate according to the evaluation by the attending physicians was 67.4%, 79.1% and 48.9% in the Z 30, Z-20 and IN groups, respectively, with a significantly higher efficacy rate for the Z-20 group than for the IN group. The frequency of adverse reactions was 14.3%, 3.9% and 5.6% in the Z-30, Z-20 and IN groups, respectively, with the highest rate in the Z-30 group, but there was no significant difference among the three groups. The useful rate based on total evaluation considering the effective rate and the safety profile in each group was 60.8%, 77.3% and 46.8% in the Z-30, Z-20 and IN groups, respectively, with the highest rate in the Z-20 group showing significant difference from that in the IN group. The above data confirmed the clinical usefulness of Z-100 and suggested that the optimal dose was 20 micrograms twice weekly for Z-100. PMID- 2235347 TI - Curriculum revolution: redefining the student-teacher relationship. PMID- 2235348 TI - Curriculum revolution: redefining the student-teacher relationship. Introduction. PMID- 2235346 TI - [Clinical efficacy of Z-100 for the treatment of leukopenia caused by radiotherapy--a multi-center double-blind comparative study with L-cysteine]. AB - The clinical usefulness of Z-100 (Z group) for the treatment of leukopenia caused by radiotherapy for malignant tumors was evaluated by comparing it with that of L cysteine (L group) by the double-blind method. For 178 complete cases, there were no significant differences in the time-course of the WBC during radiotherapy between the two group. However, for cases with a large field of irradiation (15 X 15 cm = 225 cm2), the mean WBC count in the L group decreased more than that in the Z group. The Z group showed comparable or superior efficacy for the treatment of leukopenia in the L group although there were no significant differences. Adverse reactions were observed in 5.66% and 2.94% in the Z and L groups, respectively, without any significant difference between the groups. The utility rate, useful or better, was 73.9% and 69.2% in the Z and L groups, respectively, showing a slightly higher rate in the Z group than in the L group, although the difference between the two groups was not significant. These results confirmed that Z-100 has comparable or superior efficacy to L-cysteine for the treatment of leukopenia caused by large field radiotherapy for malignant tumors. PMID- 2235349 TI - Transformation in nursing: bringing care back to health care. PMID- 2235350 TI - The two worlds of nursing: the one we teach about, the one that is. PMID- 2235351 TI - Our voices, our visions. PMID- 2235352 TI - Revolutionizing the student-teacher relationship. PMID- 2235353 TI - Curriculum revolution: a review. PMID- 2235354 TI - Has the revolution become the new religion? PMID- 2235355 TI - Critical social theory and nursing education. PMID- 2235356 TI - Clinical teaching: a shared adventure. PMID- 2235357 TI - State-approved schools of nursing L.P.N./L.V.N. 1990. PMID- 2235358 TI - Ethics in nursing: an anthology. PMID- 2235359 TI - Philosophical foundations of nursing practice. AB - This chapter examined how nursing has conceived itself historically and how this conception has changed. It is our contention, along with some of the authors discussed, that this issue is of paramount importance in structuring how a nurse responds to a moral dilemma and which obligations have primary or greater weighting. The empirical studies contained or referred to in Holfing et al. and Murphy substantiate that these conceptions do make a determinative difference in how nurses make ethical decisions. How nursing is viewed and its role relationships defined has been variously referred to as model, role conception, or philosophy of nursing. The significant point is that this forms the philosophical foundation of nursing and has profound ethical implications. The now dominant philosophy is that of client advocacy. However, as the articles indicate, ambiguity about just what advocacy entails and misgivings about the direction nursing has taken by those within and outside of nursing do exist. The next chapter presents still more conceptions of client advocacy and problems associated with it. PMID- 2235360 TI - A contrary view of the nurse as patient advocate. PMID- 2235361 TI - Patient advocacy: do nurses have the power and authority to act as patient advocate? PMID- 2235362 TI - The relation of the nurse to the doctor and the doctor to the nurse. PMID- 2235363 TI - Nursing advocacy of patients' rights: myth or reality? PMID- 2235364 TI - The nurse as advocate: a cantankerous critique. PMID- 2235365 TI - Nurses' rights. PMID- 2235366 TI - In defense of the traditional nurse. PMID- 2235367 TI - Nurses' rights. PMID- 2235368 TI - Do nurses have rights? No. PMID- 2235369 TI - Do nurses have rights? Yes. PMID- 2235370 TI - The human rights of patients, nurses, and other health professionals. PMID- 2235372 TI - The nurse-physician relationship: I. Sexism and hierarchy. PMID- 2235371 TI - A Bill of Rights for nurses. PMID- 2235374 TI - Sex discrimination: nursing's most pervasive problem. PMID- 2235373 TI - The doctor-nurse game. PMID- 2235376 TI - These men worry me. PMID- 2235375 TI - Dealing with sexism in nursing and medicine. PMID- 2235377 TI - The nurse-physician relationship: II. Somera and Tuma. PMID- 2235379 TI - The right to inform. PMID- 2235378 TI - The Somera case. PMID- 2235381 TI - Letters to the editor of Nursing Outlook: the Tuma case. PMID- 2235380 TI - Professional misconduct? PMID- 2235382 TI - Ethical reflections on the Tuma case: is it part of the nurse's role to advise on alternate forms of therapy or treatment? PMID- 2235383 TI - An experimental study in nurse-physician relationships. PMID- 2235384 TI - The nurse-physician relationship: III. Whistleblowing. PMID- 2235385 TI - Where does loyalty end? PMID- 2235386 TI - Dangerous doctors: what to do when the MD is wrong. PMID- 2235387 TI - Should nurses report negligence in medical treatment? PMID- 2235388 TI - "The 'joy' of telling a physician he's wrong". PMID- 2235390 TI - Thinking of blowing the whistle? PMID- 2235389 TI - The risks of blowing the whistle. PMID- 2235391 TI - Outrageous or outraged: a nurse advocate story. PMID- 2235392 TI - Notes of a whistleblower. PMID- 2235393 TI - Whistle-blower saved lives, lost everything else. PMID- 2235395 TI - The nurse-nurse relationship. PMID- 2235394 TI - Whistleblowing: disclosure and its consequences for the professional nurse and management. PMID- 2235396 TI - The nurse-nurse relationship. PMID- 2235398 TI - Guilt by association? PMID- 2235397 TI - Power brings out the worst in women. PMID- 2235400 TI - The commitment of nursing. PMID- 2235399 TI - Professional obligations of nurses. PMID- 2235401 TI - The nurse as a member of a profession. PMID- 2235402 TI - Engineers as moral heroes. PMID- 2235403 TI - The morality of cooperation. PMID- 2235405 TI - From loyalty to advocacy: a new metaphor for nursing. PMID- 2235404 TI - The nurse and the institution. PMID- 2235406 TI - The nurse as an employee. PMID- 2235407 TI - The conflicting demands of professionalism and unionism. PMID- 2235408 TI - Insubordination--patient load. PMID- 2235410 TI - The moral foundation of nursing. PMID- 2235409 TI - Rethinking the nurse's role in "do not resuscitate" orders: a clinical policy proposal in nursing ethics. PMID- 2235411 TI - Existential advocacy: philosophical foundations of nursing. PMID- 2235412 TI - A model for ethical decision making. PMID- 2235413 TI - The nurse as advocate. PMID- 2235415 TI - Let's stop calling ourselves "patient advocates". PMID- 2235416 TI - The nurse as advocate: concepts and controversy. PMID- 2235414 TI - The changing role of nurses in making ethical decisions. PMID- 2235417 TI - The patient rights advocate. PMID- 2235419 TI - Patient rights: an agenda for the '80s. PMID- 2235418 TI - The patient rights advocate: can nurses effectively fill the role? PMID- 2235420 TI - The role of the patient representative. PMID- 2235421 TI - The patient's representative: whose side is she on? PMID- 2235422 TI - Want some good advice? Think twice about being a patient advocate. PMID- 2235423 TI - Self-study report for home care organizations. PMID- 2235425 TI - Educational outcomes of associate degree nursing programs: roles and competencies. PMID- 2235424 TI - Self-study report for community health organizations. PMID- 2235426 TI - Taking nursing education to the streets. PMID- 2235427 TI - Community health advocacy: primary health care nurse-advocate teams in urban communities. AB - In summary, our health advocacy program uses PHC teams in urban, underserved communities to deal with the interaction of social and health factors in solving problems related to access to appropriate (as perceived by residents) and affordable health care. This approach encourages grass-roots participation in problem identification and solution, a fundamental ingredient of community empowerment. Further, this program facilitates community identification of nurses as resource persons who encourage collaboration to improve the community's health status and as health providers who enhance the authority and autonomy of community participation in the resolution of health issues. PMID- 2235428 TI - The community college-nursing home partnership: improving care through education. PMID- 2235429 TI - Lifting the veil of secrecy. PMID- 2235430 TI - Public disclosure: lifting the veil of secrecy on accreditation. PMID- 2235431 TI - Answering the question of whether success on the state boards be considered a significant outcome measure for educational programs. PMID- 2235432 TI - Should success on state boards be considered a significant outcome measure for educational programs? A regulatory perspective. PMID- 2235433 TI - An innovative method for developing a baccalaureate nursing program and providing placement credit for registered nurse students. PMID- 2235434 TI - Project L.I.N.C. (Ladders In Nursing Careers): an innovative model of educational mobility. PMID- 2235436 TI - Nurses in space. PMID- 2235435 TI - The S-S-S connection. PMID- 2235437 TI - A trajectory model for reorganizing the health care system. PMID- 2235438 TI - The many faces of the newly licensed nurse. PMID- 2235439 TI - Health policy issues toward the year 2000. PMID- 2235440 TI - Profile of hospital nursing personnel's contemporary nursing population: findings from the American Hospital Association's data. PMID- 2235441 TI - Profile of the contemporary nursing population: findings from 1988 sample survey of registered nurses data sources. PMID- 2235442 TI - Characteristics of newly licensed practical/vocational nurse practice. PMID- 2235443 TI - Costs and revenue sources for nursing centers. PMID- 2235444 TI - Nursing centers--state of the art and future initiatives: services and marketing strategies. PMID- 2235445 TI - Healing and wholeness: a case study of a nurse-managed AIDS center. PMID- 2235446 TI - A review of the state of the art of research on nursing centers. PMID- 2235447 TI - Career planning: a nurse's guide to career advancement. PMID- 2235449 TI - Nursing & health care: the supplement. PMID- 2235448 TI - Editor's notes for "Nursing in America: a History of Social Reform". A video documentary. PMID- 2235450 TI - Informatics: preparation for new nursing rules. PMID- 2235451 TI - Using simulation with RN-BSN students to challenge nursing credits. PMID- 2235452 TI - Discharge planning. Quality care: financial savings. PMID- 2235453 TI - The changing scene in baccalaureate nursing education. PMID- 2235454 TI - Nursing practice: cycles of development. PMID- 2235455 TI - Student nurse ambassadors spark interest in recruitment. PMID- 2235456 TI - Should regulatory agencies and legislative bodies dictate the curriculum of professional schools of nursing? PMID- 2235457 TI - Chemical dependency in the nursing profession. PMID- 2235458 TI - A survey of credit allocation for prior nursing education in BSN for RN programs. PMID- 2235459 TI - A theory of organizational structure for unifying nursing practice and education. PMID- 2235460 TI - The road map to a meaningful nurse preceptorship program. PMID- 2235461 TI - Nursing care shortage: strategies for resolving the crisis. PMID- 2235462 TI - Nurse empowerment: strengthening the role of research. PMID- 2235463 TI - Doctoral education for the nurse executive. PMID- 2235464 TI - Second-step versus competence-based RN baccalaureate education in a rural setting. PMID- 2235465 TI - Addressing the nursing shortage. PMID- 2235466 TI - [Bacterial meningitis in children]. PMID- 2235467 TI - [Purulent meningitis in Denmark]. AB - The epidemiology of meningococcal disease in Denmark has changed in recent years, with a rise in the number of cases in the 14-18 year age group. During the last decade 80 per cent of the meningococci belonged to Group B and 20 per cent to Group C. The treatment has followed the lines of the recommendations issued by the Rigshospitalet but some hospital departments have now chosen other preparations, as appears from the study presented in the article. PMID- 2235468 TI - [Treatment of bacterial meningitis in Finland]. AB - The Finnish recommendations for treatment of bacterial meningitis are reported in this article. A new Finnish study is the only one to present a randomised comparison of the advantages and disadvantages inherent in four major drugs against meningitis. PMID- 2235469 TI - [Bacterial meningitis in Iceland]. AB - The article reports on the number of patients in Iceland who in the last 30 years have been diagnosed as having bacterial meningitis, and on changes in the choice of medication during this period. The vaccination of Icelandic children against Haemophilus Influenzae B began in 1989. PMID- 2235470 TI - [Treatment of bacterial meningitis in Norway]. AB - Infections with Group B meningococci have been a dominant infection problem in Norway in the last 15 years. The Norwegian recommendations as to treatment are reported in the article. PMID- 2235471 TI - [2 strategies in case of meningitis in Sweden]. AB - In contrast to the other Nordic countries Sweden has long had a favourable position as regards meningococcal disease. In the last 10 year period the annual incidence has been only about one case per 100,000 inhabitants. The treatment once the cause is confirmed is conventional and no different from that in the other Nordic countries but varies somewhat in the event of unknown etiology. Cortisone therapy also seems to be more frequent in treatment of meningitis. Two strategies for antibiotic prophylaxis are used in Sweden. PMID- 2235472 TI - [Primary Sjogren's syndrome--more than a dry mouth and dry eyes]. AB - Primary Sjogren's syndrome is an autoimmune disease mainly affecting exocrine glands. The cardinal symptoms are keratoconjunctivitis sicca and xerostomia, the sicca complex, in addition to extraglandular manifestations. The diverse clinical picture and the therapeutic aspect of the syndrome are discussed. PMID- 2235473 TI - [Malignant diseases in cause-of-death autopsies in forensic medicine]. AB - The forensic examinations to determine cause of death allow study of the natural development of untreated diseases. In this study we retrospectively analysed malignant and/or intracranial tumours in a consecutive series of 7020 autopsies in northern Sweden. We found cancer in 171 cases in all, where sudden death was caused by previously undiscovered tumours in 41. PMID- 2235474 TI - [Oral temperature measurement using Craftemp]. AB - The performance of oral, electronically measured body temperature with Craftemp (Astra Meditec) in routine use in medical wards was investigated. Rectal measurement with conventional Hg-thermometer was used as a reference method. The Craftemp method turned out to be unacceptably inaccurate: 30.8 per cent of the measurements of rectal-oral temperature difference were subject to a variation around the mean larger than +/- 0.4 degree C. The standard deviation of the rectal-oral temperature differences was 0.51 degree C, and the range -1.2 degrees C to +3.0 degrees C. Until an alternative method for measurement of body temperature is proven accurate in the clinical routine, the established method of rectal measurement should not be abandoned. PMID- 2235475 TI - [General medicine in the 1990s]. PMID- 2235476 TI - [Statistical analysis of 2 x 2 tables:I. Controlled clinical studies]. PMID- 2235477 TI - [Can prevention be hazardous to health?]. AB - Health-promotion/disease-prevention may--despite the best intentions--have mischievous effects and overlooked ethical implications. This article describes some consequences of health promotion when initiated by the medical profession as medicalization of the modern human being, problems with false test-results, iatrogenic disease, and the risk of "victim blaming". The responsibility of the medical profession includes the well-being of healthy people as well as the actually or future sick. Therefore, health promotion has to be based on the values and informed consent of the healthy part of the population. PMID- 2235478 TI - [Surgery at high altitude--greetings from a hospital in the Himalayas. Tropical surgery--about typhoid perforation and tiger bites]. PMID- 2235479 TI - Sequence analysis of two temperature-sensitive mutations in the alpha subunit gene (rpoA) of Escherichia coli RNA polymerase. AB - The rpoA gene of Escherichia coli encodes the alpha subunit of the DNA-dependent RNA polymerase. Two mutant alleles, rpoA101 and rpoA112, both of which produce RNA polymerase with altered thermostability and reduced fidelity of transcription in vitro (Ishihama et al. (1980) J. Mol. Biol. 137, 137-150), have been analyzed in details. The mutations were found to be responsible for the temperature sensitive growth by complementation test using a rpoA-expression plasmid. Each mutant allele was amplified from total cell DNA by PCR (polymerase chain reaction) and directly sequenced. Both the mutant rpoA genes were found to carry a single base transition which leads to a substitution of Cys for Arg at the position 191 (rpoA101) or 45 (rpoA112), respectively. Since the rpoA112 mutation causes the defect in RNA polymerase assembly (Kawakami & Ishihama (1980) Biochemistry 19, 3491-3495), the amino-terminal region of alpha including the position 45 was considered to play an important role in subunit assembly. PMID- 2235480 TI - 'Compensatory slippage' in the evolution of ribosomal RNA genes. AB - The distribution patterns of shared short repetitive motifs in the expansion segments of the large subunit rRNA genes of different species show that these segments are coevolving as a set and that in two examined vertebrate species the RNA secondary structures are conserved as a consequence of runs of motifs in one region being compensated by complementary motifs in another. These unusual processes, involving replication-slippage, have implications for the evolution of ribosomal RNA and for the use of the rDNA multigene family as a 'molecular clock' for assessing relationships between species. PMID- 2235481 TI - Identification and structural characterization of O-beta-ribosyl-(1"----2') adenosine-5"-phosphate in yeast methionine initiator tRNA. AB - We report in this paper on the complete structure determination of the modified nucleotide A*, now called Ar(p), that was previously identified in yeast methionine initiator tRNA as an isomeric form of O-ribosyl-adenosine bearing an additional phosphoryl-monoester group on its ribose2 moiety. By using the chemical procedure of periodate oxidation and subsequent beta-elimination with cyclohexylamine on mono- and dinucleotides containing Ar(p), we characterized the location of the phosphate group on the C-5" of the ribose2 moiety, and the linkage between the two riboses as a (1"----2')-glycosidic bond. Since the structural difference between phosphatase treated Ar(p) and authentic O-alpha ribosyl-(1"----2')-adenosine from poly(ADP-Ribose) was previously assigned to an isomeric difference in the ribose2-ribose1 linkage, the (1"----2')-glycosidic bond of Ar(p) was deduced to have a beta-spatial configuration. Thus, final chemical structure for Ar(p) at the position 64 in yeast initiator tRNA(Met) has been established as O-beta-ribosyl-(1"----2')-adenosine-5"-phosphate. This nucleotide is linked by a 3',5'-phosphodiester bond to G at the position 65. PMID- 2235482 TI - Control of mRNA stability in chloroplasts by 3' inverted repeats: effects of stem and loop mutations on degradation of psbA mRNA in vitro. AB - To investigate the role of mRNA 3' inverted repeats (IRs) in stabilizing plant chloroplast mRNAs, we have measured the processing and stability of wild-type and mutant RNAs corresponding to the 3' end of the spinach chloroplast psbA mRNA. wild-type and mutant 3' IR-RNA precursors were processed at similar rates in a homologous in vitro system, but RNAs with either a mutant loop sequence CUUCGG or a specific base substitution in the IR exhibited an enhanced accumulation of mature product. Incubation of mature products in the in vitro system demonstrated that this was due to an increased stability of the product. These mutant RNAs displayed the same order of stabilities when their decay was measured following electroporation into intact chloroplasts. We found that the in vitro system contains an endonuclease activity that cleaves the wild-type 3' IR-RNA within the loop and also in single-stranded regions, suggesting a possible role for the loop sequence in determining RNA longevity in vitro. Interestingly, the altered loop sequence CUUCGG, which enhances RNA stability in bacteria (1), prolonged the half life of psbA 3' IR-RNA in vitro and also resulted in an altered endonuclease cleavage pattern. Such nucleases could potentially play an important role in plastid mRNA decay in vivo. PMID- 2235483 TI - Inducibility of the HS II enhancer depends on binding of an erythroid specific nuclear protein. AB - An erythroid specific, inducible enhancer associated with hypersensitive site II (HS II) plays a central role in the function of the human beta globin dominant control region. The HS II enhancer consists of tandem AP-1 binding sites and has been shown to bind members of the ubiquitous jun and fos families of proteins. The same sites are now shown to bind the erythroid specific protein, NF-E2. Inducibility of the HS II enhancer depends on NF-E2 binding, even in the presence of another hypersensitive site. Further, increased activity of the enhancer in induced K562 cells correlates with the presence of NF-E2, which appears to be present in a modified form. NF-E2 is distinct from some enhancer binding proteins in K562 nuclear extracts, in that it does not contain Fos or Fra-1 protein. Thus, binding by NF-E2 may be the mechanism, whereby tandem AP-1 binding sites confer erythroid specificity on the HS II enhancer. PMID- 2235484 TI - Thiophosphate interference experiments locate phosphates important for the hammerhead RNA self-cleavage reaction. AB - A hammerhead domain of less than 50 nucleotides is responsible for a self cleavage reaction in the replication of plant RNA pathogens. The hammerhead is composed of three helices joining at a central conserved core of 11 single stranded nucleotides. The core is believed to fold into a tertiary structure that provides functional groups for catalysis and to coordinate one or more divalent metal ions. In this study we use a phosphorothioate substitution interference assay to identify four phosphates in the conserved core which also play a role in the self-cleavage reaction. PMID- 2235485 TI - Chromosomal footprinting of transcriptionally active and inactive oocyte-type 5S RNA genes of Xenopus laevis. AB - The chromatin structure of the Xenopus oocyte-specific 5S rRNA genes was examined at high resolution in immature oocyte and somatic cell chromosomes by DNase I footprinting. On oocyte chromatin, where the genes are active, the cleavage preferences over the entire gene region showed a periodic pattern of sensitivity and were dramatically different from the patterns obtained with deproteinized DNA or somatic cell chromatin. Further, the normal binding site for TFIIIA over the internal promoter region was preferentially sensitive to cleavage, indicating that TFIIIA was not bound in the manner predicted by in vitro experiments. In somatic cell chromatin, the oocyte-type 5S genes displayed a cleavage pattern largely similar to deproteinized DNA suggesting the absence of positioned nucleosomes on these inactive genes, although the presence of uncharacterized repressor complexes could not be ruled out. These data are discussed in terms of potential forms of the chromatin structure and alternative mechanisms of oocyte type gene activation. PMID- 2235486 TI - Host sequences flanking the HIV provirus. AB - A conserved property of retroviral proviruses is the presence of a direct repeat in the host DNA immediately flanking the viral sequence; each virus generates a repeat with a characteristic length. By sequencing the viral/host DNA junctions from five HIV-1 proviral clones, we have confirmed that integration of HIV results in the generation of a five basepair direct repeat. A target sequence in uninfected host DNA was analyzed to establish that the five basepair sequence flanking the provirus was present only once prior to integration. Of the five proviruses examined, two were found to have integrated in known repetitive sequence elements of the human genome; one in a Line-1 element and a second in satellite DNA. PMID- 2235487 TI - Metal-dependent binding of a nuclear factor to the rat metallothionein-I promoter. AB - Genomic footprinting studies in vivo and experiments using synthetic metal regulatory elements (MREs) in vitro suggest protein binding to the MREs of the mouse and rat metallothionein I (MT-I) genes. Using gel-retardation assays of promoter fragments, we observe a cadmium-dependent binding factor for the rat MT I promoter in rat hepatoma cells. This factor is present in extracts from both uninduced and cadmium-induced cells, but requires the presence of cadmium to bind to the promoter. The formation of a cadmium-dependent complex is competed by an oligonucleotide containing two MREs. This competition is lost when when one of the MREs is mutated, indicating a requirement for at least two MREs for binding of this factor. The cadmium-dependent factor dissociates more rapidly from the MT I promoter than does a factor that binds to a consensus Sp1 site present on the same DNA fragment. UV crosslinking analysis using nuclear extracts from cadmium induced cells, in the presence of an oligonucleotide probe containing both 5 bromodeoxyuridine and 32P-deoxycytidine, identifies a 39 kDalton protein associated with the metal inducible complex. PMID- 2235488 TI - The stability of polypurine tetraplexes in the presence of mono- and divalent cations. AB - As with other guanine-rich sequences, poly[d(GGA)], poly[d(GA)] and poly[d(GAA)] probably form four-stranded or tetraplex structures. Thermal denaturation profiles were measured for these polymers at pH8 in the presence of Na+, NH4+, K+, Cs+, Mg2+, Ca2+ and Ba2+. For poly[d(GA)], Na+, NH4+, K+ stabilize the tetraplex to similar extents and the Tm increases with increasing ionic strength. In contrast the Tms with Mg2+, Ca2+ and Ba2+ are significantly different and reach maxima at about 5mM of cation. The tetraplex from poly [d(GAA)] behaves in a similar manner. Thermal denaturation profiles for poly[d(GGA)] yield transitions whose hyperchromicity depends both on the concentration and nature of the ion. A reversible cooperative transition is not observed at concentrations greater than 0.15M K+, 1mM Ca2+ or 0.3 mM Ba2+ and hysteresis is evident at some concentrations. These results are consistent with the idea that K+ and ions of a similar size can form a coordination complex with the 6-Keto group of eight guanines (G8-DNA). Unlike the tetraplex polymer this G8-DNA does not melt cooperatively. PMID- 2235489 TI - DNA sequences required for yeast actin gene transcription do not include conserved CCAAT motifs. AB - Sequences required for Saccharomyces cerevisiae actin gene transcription were mapped and compared to the regulatory region of the actin gene from a thermophilic fungus, Thermomyces lanuginosus. Two CCAAT motifs conserved in position in these two species could be mutated without affecting promoter activity, regardless of whether the yeast were grown in fermentable or non fermentable carbon sources. Two TATA-like sequences and an upstream activation sequence (UAS) composed of multiple elements were identified. The contribution of sequence motifs within these elements to UAS activity varied depending on the carbon source. The Thermomyces gene contains sequences highly homologous to this UAS, but in the opposite orientation. PMID- 2235490 TI - Ligation-independent cloning of PCR products (LIC-PCR). AB - A new procedure has been developed for the efficient cloning of complex PCR mixtures, resulting in libraries exclusively consisting of recombinant clones. Recombinants are generated between PCR products and a PCR-amplified plasmid vector. The procedure does not require the use of restriction enzymes, T4 DNA ligase or alkaline phosphatase. The 5'-ends of the primers used to generate the cloneable PCR fragments contain an additional 12 nucleotide (nt) sequence lacking dCMP. As a result, the amplification products include 12-nt sequences lacking dGMP at their 3'-ends. The 3'-terminal sequence can be removed by the action of the (3'----5') exonuclease activity of T4 DNA polymerase in the presence of dGTP, leading to fragments with 5'-extending single-stranded (ss) tails of a defined sequence and length. Similarly, the entire plasmid vector is amplified with primers homologous to sequences in the multiple cloning site. The vector oligos have additional 12-nt tails complementary to the tails used for fragment amplification, permitting the creation of ss-ends with T4 DNA polymerase in the presence of dCTP. Circularization can occur between vector molecules and PCR fragments as mediated by the 12-nt cohesive ends, but not in mixtures lacking insert fragments. The resulting circular recombinant molecules do not require in vitro ligation for efficient bacterial transformation. We have applied the procedure for the cloning of inter-ALU fragments from hybrid cell-lines and human cosmid clones. PMID- 2235491 TI - Synthesis of a gene for human serum albumin and its expression in Saccharomyces cerevisiae. AB - A 1761 base pairs long artificial gene coding for human serum albumin (HSA) has been prepared by a newly developed synthetic approach, resulting in the largest synthetic gene so far described. Oligonucleotides corresponding to only one strand of the HSA gene were prepared by chemical synthesis, while the complementary strand was obtained by a combination of enzymatic and cloning steps. 24 synthetic, 69-85 nucleotides long oligonucleotides covering the major part of the HSA gene (41-1761 nucleotides) were used as building blocks. Generally, four groups of 6-6 such oligonucleotides were successively cloned in pUC19 Escherichia coli vector to obtain about quarters of the gene as large fragments. Joining of these four fragments resulted in a cloned DNA coding for the 13-585 amino acid region of HSA, which was further supplemented with a double stranded linker sequence coding for the amino terminal 12 amino acids. The completed structural gene composed of frequently used codons in the highly expressed yeast genes was then supplied with yeast regulatory sequences and the HSA expression cassette so obtained was inserted into an Escherichia coli Saccharomyces cerevisiae shuttle vector. This vector was shown to direct the expression in Saccharomyces cerevisiae of correctly processed, mature HSA which was recognized by antiserum to HSA, and possessed the correct N-terminal amino acid sequence. PMID- 2235492 TI - Adenovirus infection of differentiated F9 cells results in a global shut-off of differentiation-induced gene expression. AB - Previous experiments have demonstrated a link between transcriptional regulatory mechanisms acting during F9 cell differentiation and transcription control by the adenovirus E1A gene. We have isolated a number of differentiation-specific genes by cDNA cloning to determine if E1A exerts a coordinated control over differentiation specific gene expression. The mRNAs encoded by these cDNAs were undetectable or only barely detectable in undifferentiated cells but then rose in concentration upon differentiation. Analysis of transcription rates in isolated nuclei revealed that all but one of the genes was transcriptionally regulated during differentiation. Interestingly, alpha 2-type IV collagen expression was activated by a post-transcriptional mechanism since the gene was transcribed in both undifferentiated and differentiated cells whereas the cytoplasmic mRNA was undetectable in undifferentiated cells but rose in abundance in parallel with other regulated transcripts. Adenovirus infection of differentiated F9 cells reduced the cytoplasmic mRNA levels of each of the differentiation specific genes to near that found in the undifferentiated cell. Of those genes that were transcriptionally activated by differentiation, adenovirus infection specifically inhibited transcription. In contrast, although the alpha 2 collagen mRNA levels were reduced by adenovirus infection similar to the other mRNAs, the control was post-transcriptional since transcription of the gene was unaffected. Thus, the mechanism for loss of gene expression mediated by E1A reflects the mechanism by which the gene was activated during differentiation. Based on these results we suggest that E1A controls the expression of the F9 cell phenotype by targeting a regulatory activity acting early in the differentiation program. PMID- 2235493 TI - Evidence for the frequent use of TTG as the translation initiation codon of mitochondrial protein genes in the nematodes, Ascaris suum and Caenorhabditis elegans. AB - Data obtained from alignments of nucleotide sequences of mitochondrial (mt) DNA molecules of the nematode worms Ascaris suum and Caenorhabditis elegans indicate that in six of the mt-protein genes of A. suum and three of the mt-protein genes of C. elegans TTG is used as the translation initiation codon. Also, GTT seems to be the translation initiation codon of the A. suum COIII gene. All of the five remaining A. suum mt-protein genes appear to begin with ATT and the remaining nine C. elegans mt-protein genes appear to begin with either ATT or ATA. Therefore, in contrast to all other metazoan mtDNAs sequenced so far, it is likely that none of the nematode mt-protein genes use the standard ATG translation initiation codon. Some A. suum and C. elegans mt-protein genes end in T or TA, suggesting that, as found in other metazoan mitochondria, 3'-terminal polyadenylation is occasionally necessary to generate complete translation termination codons in transcripts of nematode mt-protein genes. PMID- 2235495 TI - Conservation of the 3' terminal nucleotide sequence in five carlaviruses. PMID- 2235494 TI - Evidence for a new Z-type left-handed DNA helix: properties of Z(WC)-DNA. AB - The structure of Z-DNA, currently accepted as a model for all left-handed DNAs, fails to provide convincing explanations for at least four well established properties of left-handed DNA polymers in solution. However, the major discrepancies between theory and experiment are resolved by the structure presently proposed for Z[WC]-DNA, a new left-handed, zig-zag double helix with Watson-Crick-type backbone directions. Structural features of Z[WC]-DNA include the presence of an additional H-bond between each guanine N2-amino group and an adjacent phosphate oxygen, the capacity to form four-stranded, base-matched complexes that should readily precipitate from solution, and backbone progressions that are the same as B-DNA (opposite to Z-DNA). However, since Z[WC] DNA and Z-DNA have many parameters in common, they could be difficult to distinguish in a majority of existing experiments. In view of the close relationship of the new helix to B-DNA, which allows a relatively unhindered right-to-left transition in handedness, Z[WC]-DNA is theorized to be the left handed structure preferentially generated in vivo by the torque available in naturally occurring DNA supercoils. PMID- 2235496 TI - Nucleotide sequence of rfaI and rfaJ genes encoding lipopolysaccharide glycosyl transferases from Salmonella typhimurium. PMID- 2235497 TI - Nucleotide sequence of guinea-pig kappa-casein cDNA. PMID- 2235498 TI - The nucleotide sequence of the ferrochelatase and tRNA(val) gene region from Saccharomyces cerevisiae. PMID- 2235499 TI - Cloning and sequencing of POU-boxes expressed in Xenopus laevis neurula embryos. PMID- 2235500 TI - Nucleotide sequence of a radish cDNA clone coding for a late embryogenesis abundant (LEA) protein. PMID- 2235501 TI - Complete nucleotide sequence of the aroA gene from Salmonella typhi encoding 5 enolpyruvylshikimate 3-phosphate synthase. PMID- 2235502 TI - Nucleotide sequence of two proline tRNA (AGG and CGG) genes from chicken. PMID- 2235503 TI - The nucleotide sequence of Xenopus laevis transferrin mRNA. PMID- 2235504 TI - Nucleotide sequence of the major outer membrane protein gene of Chlamydia trachomatis strain A/SA1/OT. PMID- 2235505 TI - Nucleotide sequence of the virion protein gene of belladonna mottle tymovirus. PMID- 2235507 TI - Complete nucleotide sequence of a German duck hepatitis B virus. PMID- 2235506 TI - Complete nucleotide sequence of a Chinese duck hepatitis B virus. PMID- 2235508 TI - Cloning and sequencing of the cysteine protease cDNA from Trypanosoma brucei rhodesiense. PMID- 2235509 TI - Nucleotide sequence of HIV-2D194, an isolate from a Gambian case of 'neuro-AIDS', which showed excellent growth in macrophages. PMID- 2235510 TI - Nucleotide sequence of rice 4-coumarate:CoA ligase gene, 4-CL.1. PMID- 2235511 TI - The complete sequence of the Bacillus amyloliquefaciens strain H, cellular BamHI methylase gene. PMID- 2235512 TI - The absence of adenine methylation increases the ligation efficiency of partially filled staggered DNA ends. PMID- 2235513 TI - Use of gamma irradiation to eliminate DNA contamination for PCR. PMID- 2235514 TI - A quick and efficient method for the recovery of plasmid or viral DNA from mammalian cells. PMID- 2235515 TI - DNA isolated from plastic embedded tissue is suitable for PCR. PMID- 2235516 TI - Stable and safe HIV provirus clones. PMID- 2235517 TI - Isolation and identification of restriction endonuclease Asp35HI from Acidiphilium species 35H. PMID- 2235518 TI - A simple method for generating single-stranded DNA probes labeled to high activities. PMID- 2235519 TI - A rapid and efficient method for transcript mapping. PMID- 2235520 TI - Direct single stranded sequencing from agarose of polymerase chain reaction products. PMID- 2235521 TI - Transferring plasmid DNA between different bacterial species with electroporation. PMID- 2235522 TI - A simple method for the direct use of total cosmid clones as hybridization probes. PMID- 2235523 TI - Ligated mycoplasma genomes as DNA size markers for PFGE. PMID- 2235524 TI - A rapid and highly efficient method for preparation of competent Escherichia coli cells. PMID- 2235525 TI - An STS in the human T cell receptor gamma locus (located at 7p14-15). PMID- 2235526 TI - G to A polymorphism in exon 31 of the COL3A1 gene. PMID- 2235528 TI - Retraction. Nucleotide sequences of mitochondrial ATPase subunit 9 genes from three lines of rice (Oryza Sativca L.) PMID- 2235529 TI - Questions the foundation of nursing education. PMID- 2235530 TI - Less caring and more self-caring. PMID- 2235531 TI - Military as model for caring? PMID- 2235532 TI - News for the passing parade. PMID- 2235527 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2235533 TI - The aftermath of the Cruzan decision: dying in a twilight zone. PMID- 2235534 TI - The Oregon plan: increasing access to health care. AB - In 1989, a coalition of Oregon legislators, policymakers, and health care professionals created a new plan that attempts to ensure equitable and universal access to health care by prioritizing types of care. Critics call it unrealistic and a dangerous rationing scheme. Proponents argue it is better than the current system that denies thousands of citizens access to basic care. PMID- 2235535 TI - Nurses make high tech high touch. AB - Until nurses at St. Mary's Hospital took the lead in establishing an outpatient infusion unit, oncology patients had to travel up to 100 miles to receive chemotherapy. Today, they need travel only ten minutes to receive the best and latest of a variety of high-tech services. PMID- 2235536 TI - Assessment preparation for nurse practitioners. AB - Faced with primary care graduate students who were not adequately prepared to meet the demands of their clinical courses, faculty at the University of Pennsylvania conducted a three-year study to determine the effectiveness of physical assessment prerequisites. They concluded that graduate level assessment preparation was well worth the time and effort such courses require. PMID- 2235537 TI - An early 20th century view of nursing. AB - The novels of Dorothy Canfield Fisher reflect the esteem with which nursing was held in the first half of the 20th century. Though no longer widely read, these novels were, in their day, ranked with those of Willa Cather, Pearl Buck and Edith Wharton and are distinguished by their portrayal of nurses as strong, competent, independent, and compassionate role models for young women. PMID- 2235538 TI - Do patients understand written health information? AB - Long sentences, medical terms and small print make hospital information brochures and consent forms difficult for many patients to understand. There are, however, things nurses can do to make written information for patients more accessible. PMID- 2235539 TI - Should continuing education be public policy? AB - A survey of Illinois registered nurses reveals a striking relationship between employment setting and participation in continuing education programs. It suggests that public policy mandating CE participation may not be the best way to increase such participation among those nurses least inclined to do so. PMID- 2235540 TI - Ethical issues in research: scientific misconduct and fraud. PMID- 2235541 TI - AIDS support. PMID- 2235542 TI - Pay Review Body. The pay body snatchers. PMID- 2235543 TI - Pay Review Body. The cost of trusting. PMID- 2235544 TI - Pay Body Review. We don't want to fight, but .... PMID- 2235546 TI - Is stripe-itis curable? PMID- 2235545 TI - Pay Body Review. Breaking away. PMID- 2235547 TI - Alcoholism. To hell and back. PMID- 2235548 TI - Alcoholism. Small steps to progress. PMID- 2235549 TI - Eastern Europe. Training a new generation. PMID- 2235550 TI - Making sense of .... Endotracheal intubation. PMID- 2235551 TI - Stamping out inequality. PMID- 2235553 TI - Measuring quality in a psychiatric hospital. PMID- 2235552 TI - Alternative techniques. PMID- 2235554 TI - Nursing overseas. Operation Ontario. PMID- 2235555 TI - Her own brand of humour. Interview by Ian McMillan. PMID- 2235556 TI - Latchkey children. PMID- 2235557 TI - Investigating casual transmission of HIV. PMID- 2235559 TI - Women's health and nursing work. PMID- 2235558 TI - The measurement of symphyseal-fundal height. PMID- 2235560 TI - Primary nursing. An associate in care. PMID- 2235562 TI - Primary nursing. Collegiality is the key. PMID- 2235561 TI - Primary nursing. A role, not a title. PMID- 2235563 TI - Fewer than expected HIV children. PMID- 2235564 TI - Painful admission. PMID- 2235565 TI - Taking liberties. PMID- 2235566 TI - Widening horizons. PMID- 2235567 TI - Air of danger. PMID- 2235568 TI - Signals for support. PMID- 2235569 TI - Open learning. Into a new era. PMID- 2235570 TI - Open learning. The right stuff. PMID- 2235571 TI - Open learning. What the punters say. PMID- 2235572 TI - Thorns in their side? PMID- 2235573 TI - Making the game safer. PMID- 2235574 TI - Rehabilitation and the cancer patient. PMID- 2235575 TI - Seasonal affective disorder. Winter depression. PMID- 2235576 TI - Seasonal affective disorder. A sad situation. PMID- 2235577 TI - Farewell to the polyclinics? PMID- 2235579 TI - Drug administration. The view from the pharmacy. PMID- 2235578 TI - Drug administration. A prescription for self-help. PMID- 2235581 TI - Nurses and the law. Ethical ways. PMID- 2235580 TI - Professional conduct. Past imperfect. PMID- 2235582 TI - Intermittent self-catheterisation. PMID- 2235583 TI - Do we need to clamp catheters? PMID- 2235584 TI - Paediatrics needs to consider HIV. PMID- 2235586 TI - Open mind. PMID- 2235585 TI - Occupational hazards. PMID- 2235587 TI - Shifting ground. PMID- 2235588 TI - Child's play. PMID- 2235589 TI - Modern theatre. PMID- 2235590 TI - Undervalued support. PMID- 2235591 TI - Time to make doughnuts? PMID- 2235592 TI - Against the odds. PMID- 2235593 TI - Fair deal on appeal. A bottomless pit? PMID- 2235594 TI - Drug administration. Doing the round alone. PMID- 2235595 TI - Drug administration. Breaking the chain reaction. PMID- 2235596 TI - A jaundiced view. PMID- 2235597 TI - Improving social skills. PMID- 2235598 TI - HIV infection and community nursing staff in Scotland--1. Experience, practice and education. AB - To assess the effects of human immunodeficiency virus (HIV) for the work of community nursing staff, and to find out how community staff regard their contribution to the prevention of HIV infection, the care of people with AIDS and their preparation for this role was ascertained in a postal survey of one in five field staff carried out in Scotland. The 1,205 respondents represent an 85% response rate. While only 3% of respondents had experience of patients with AIDS, 11% had been involved with known asymptomatic HIV infection and 30% had encountered those they considered to be at high risk of infection. While the workload generated by HIV-infected patients for individual nurses at this time was small, there were variations in the proportions of staff involved according to type of staff and employing health board. Only one-fifth of those who had encountered HIV-positive patients had offered them health education, and fewer had referred patients to their general practitioners or offered counselling. However, community nursing staff do consider that they have a role to play in health education, counselling and terminal care, but feel ill equipped to carry out this role. There is an urgent need for policies which clearly specify the roles that community nursing staff should be playing and for in-service education programmes which assist them to draw on the knowledge and skills that they have to enable them to apply them to help patients with HIV infection. PMID- 2235599 TI - Assessing methods of lipid measurement. PMID- 2235600 TI - Screening tests for sensorineural deafness. PMID- 2235601 TI - Essential hypertension in pregnancy. PMID- 2235602 TI - Management. A welcome return? PMID- 2235604 TI - Health visitors' supplement. Water, water everywhere.... PMID- 2235603 TI - 'Donkeys' and dinner duty. PMID- 2235606 TI - Health visitors' supplement. Shouting it out. PMID- 2235605 TI - Health visitors' supplement. Business as usual. PMID- 2235607 TI - Health visitors' supplement. Bottom of the league? PMID- 2235608 TI - Health visitors' supplement. After the honeymoon. PMID- 2235609 TI - Reflex labelling of high-risk individuals does not limit HIV. PMID- 2235610 TI - Pink problems, blue solutions. Interview by Linda Davidson. PMID- 2235611 TI - Strengthening ties. PMID- 2235612 TI - Sanctuary in peril. PMID- 2235614 TI - Happily ever after? PMID- 2235613 TI - Vitamin alert. PMID- 2235615 TI - Nursing homes. Buyer beware. PMID- 2235616 TI - Nursing homes. Home truths. PMID- 2235617 TI - Nursing homes. Monitoring muddles. PMID- 2235618 TI - Sporting life. PMID- 2235619 TI - Making sense of .... hydrocolloid dressings. PMID- 2235620 TI - Nurses' homes. There's no place like home? PMID- 2235621 TI - Nurses' homes. Action plan for improvements. PMID- 2235622 TI - Fair deal on appeal. No way up. PMID- 2235623 TI - Facing the challenge. PMID- 2235624 TI - HIV infection and community nursing staff in Scotland--2. Knowledge and attitudes. AB - Findings from a survey of community nursing staff in Scotland reveal that there is limited knowledge about many aspects of HIV infection. Respondents were concerned about their lack of experience and knowledge as well as the in-service education that they had received. A substantial minority of community nursing staff felt that they should have the right to refuse to care for HIV-infected patients and those whose lifestyle put them at risk of HIV infection. A majority of staff felt that health professionals who are most at risk of contact with HIV infected materials should be informed of patients' HIV-antibody status without their consent. There were also some indications of a lack of confidence in service managers and recommendations are made regarding ways of increasing both the knowledge and confidence of front-line staff. PMID- 2235625 TI - 40 years on. PMID- 2235626 TI - Nurse education. Preaching what they practise. PMID- 2235627 TI - Nurse education. How to ... evaluate a short course. PMID- 2235628 TI - Mum's the word. PMID- 2235629 TI - Eliciting assessment data from the patient who is difficult to interview. AB - The patient interview is an essential part of the assessment phase of the nursing process. Ensuring a productive interview involves controlling, as much as possible, the interview environment as well as the nurse's verbal and nonverbal communication. Patients who are cognitively impaired, angry, anxious, depressed, manipulative, or seductive can make this interview process more challenging. Working individually with each of these possible patient dynamics in a calm, controlled, and knowledgeable way can help facilitate the interview process and pave the way for fewer problems in the future. Frequently, the interview may involve the discussion of sensitive topics such as terminal illness, suicide, or sexuality. Gathering information and developing a comfort level in broaching these issues with patients are important goals for nursing professionals. Reading, attending workshops, consultation with professionals, and most important, self-assessment of these sensitive topics are all useful tools in obtaining those goals. PMID- 2235630 TI - Assessment of patient laboratory data in the acutely ill. AB - Laboratory test results are a valuable source of information. Nurses need to assess laboratory test results as part of the physical assessment of their patients. Comparison of laboratory test results and changes with abnormal physical findings provides the basis for changes in the nursing care plan. Progressive monitoring of laboratory results and prompt interventions might lessen the seriousness of the health problem. In acute care units, the initial group of laboratory tests serves as a baseline for assessing additional test results. Several reference values should be remembered, particularly the electrolytes (potassium, sodium, and calcium), glucose, BUN, creatinine, and albumin. Specific group profiles assist in identifying and in monitoring the patient's health status. Incorporating laboratory test results into the plan and evaluation of care will result in safer and more effective patient care. Referring to laboratory test findings and comparing them with physical assessment findings are required for the delivery of professional nursing care. PMID- 2235631 TI - Pulmonary and acid-base assessment. AB - With increased technology, increased patient longevity, and burgeoning health care knowledge, pulmonary assessment of clients has become more complex, and nurses are now challenged to develop more comprehensive skills. These include a more focused patient history on selected clients as well as careful inspection, palpation, percussion, and auscultation. Additional techniques such as voice sounds provide the nurse with even more assessment data. An understanding of common pathologic pulmonary problems and their corresponding assessment findings as well as knowledge about acid-base imbalances will result in more effective professional nursing care. PMID- 2235632 TI - Advanced assessment of the abdomen and gastrointestinal problems. AB - There are many unique physical assessment findings that are associated with specific gastrointestinal disorders. The detection of these findings enables the nurse to manage gastrointestinal emergencies on the patient unit in a timely fashion, preventing deterioration and maintaining the safety of the patient. These skills build well on the traditional, detailed, and comprehensive assessments the nurse makes when using the nursing process. Specific abdominal assessments include detection of signs associated with appendicitis such as rebound tenderness and McBurney's, Rosvig's, and Aaron's signs. The nurse must always be alert to the possibility of peritonitis and the urgency of early detection and treatment. The patient with cirrhosis of the liver presents a distinct clinical picture. There is a need for subtle evaluation of mental status to detect early signs of hepatic coma. Another extra-abdominal assessment of this complication is asterixis. Finally, the assessment of the patient is enhanced when the nurse is able to help identify the location of bleeding. Improving abdominal and gastrointestinal system assessment leads to early detection of nursing problems and appropriate interventions. PMID- 2235633 TI - Peripheral vascular disorders. Assessment and intervention. AB - Peripheral vascular diseases are being seen with increased frequency in the health care setting today. It is imperative that nurses have a clear understanding of arterial, venous, and lymphatic circulatory mechanisms as well as the pathophysiologic changes that accompany common diseases of these systems. Providing the ongoing assessment to obtain a diagnosis, establish the acute versus chronic nature of findings, monitor progression, plan care, and assess the response to treatment is an important role for the nurse in order to preserve function, life, and limb in these patients. PMID- 2235634 TI - Neurologic assessment. AB - Neurologic nursing assessment requires the knowledge of anatomic and physiologic principles as well as the mastery of complex assessment skills. The nurse who is often the first and most consistent health team member interacting with clients may provide the key to the early recognition, prevention, and treatment of neurologic problems. The nurse, as the dynamic member of the health team, may then be the first line of defense in initiating cost-effective and perhaps life saving measures in neurologically impaired clients. PMID- 2235635 TI - Assessing acquired ocular diseases. AB - When assessing a patient's ocular complaint, one must listen carefully to the description of the symptoms. A decrease in vision is most frequently the symptom that prompts a person to seek attention. Pain in and around the eye is the next most frequent symptom complained about. Discomfort is often tolerated for long periods before professional attention is obtained. Visual acuity must be checked, for this is the vital sign by which exacerbation or improvement of many conditions is measured. We all take our eyes for granted until we suddenly cannot see, then the world takes on a completely different complexity, for loss of vision may mean loss of livelihood and independence. PMID- 2235636 TI - Health assessment of the early adolescent. Challenges and clinical issues. AB - Although early adolescence spans only 4 years, it is a critical time in the life of a young person in forming opinions and selecting options. Specific attention to the growing and changing needs of this population is imperative if their health status is to improve. PMID- 2235637 TI - The older adult. A comparative assessment. AB - Thorough assessment of older men and women is a complex but vital part of their health care. The ability to differentiate the changes owing to normal aging from those resulting from pathologic processes is necessary if their lives are to be as productive and enjoyable as they are prolonged. Each body system and function must be examined or tested with this difference in mind. Because aging occurs in different individuals at differing rates, a variety of functions may all be considered healthy or normal. Assessment findings must be viewed through the focus of the individual person as well as that of the population. The nurse will find opportunities to use assessment skills for older adults in many settings, ranging from independent living arrangements to institutional residential areas. In the community, social meeting places, day-care facilities, meal sites, and shopping areas are but a few of the places where older adults may be found, alone or in groups. Assessment opportunities can be identified or structured in any milieu. The setting itself, as well as the needs of the older adult(s), will help to determine the complexity of the assessment activities. The benefit to nursing of increased and expanded ability to assess the older adult is considerable. The organized concern of science and health care with aging is a relatively recent phenomenon. The older adults of today are unique--there are more of them than ever before, and they are living longer. Although their lives are not without health complications, they are, in a sense, role models for the rest of us: pathfinders in aging who can, if we observe them carefully, give us insight and direction for our own healthy aging processes and those of generations to come. Nursing is uniquely poised to use our caring methodology with the older adult. The elderly are interested in their health and willingly cooperate with those whose assessments are knowledgeable and realistic. Nursing is challenged to develop and implement advanced and specialized ways to identify and meet their needs. PMID- 2235638 TI - Acute pain relief. AB - Pain is a multidimensional psychophysiologic phenomenon. Systematic multidimensional assessment is an essential first component of an effective plan to relieve the pain. Nurses are key to effective pain management because of the close, 24-hour-a-day relationship with the hospitalized patient. It is the nurse who is most critical to the adequate assessment of pain, to the implementation of the treatment plan, and to the evaluation of efficacy. Nurses should continue to develop a better knowledge base about pain and pain therapies and assessment skills, be assertive in obtaining effective treatment for their patients, and perceive themselves as responsible for pain relief. PMID- 2235639 TI - Chronic pain. AB - Understanding of the etiology of chronic pain is growing rapidly as researchers seek to integrate physiologic and psychosocial mechanisms. When nurses assess clients with chronic pain, they should make their assessments using both verbal and nonverbal methods and realize that no one instrument is comprehensive enough to be used alone. The key to successful treatment of these difficult clients lies in the use of a comprehensive approach that takes the client seriously and integrates both physiologic and psychosocial approaches. PMID- 2235640 TI - Pain in children. AB - The assessment and management of children's pain is a topic that has received a great deal of attention since the late 1970s. Nurse researchers have played a dominant role in all areas of pediatric pain relief and likely will continue to do so. There are currently a number of pediatric pain assessment instruments developed that are used in selected practice settings, but their use should be extended to document the existence of pediatric pain and its relief. Pharmacologic interventions for pediatric pain relief have been hampered by incorrect beliefs about analgesic risks, prescribing and administrating habits, and a virtual explosion of information in the area of analgesics. Although nurses have traditionally used nonpharmacologic interventions for pain relief, these methods have not been well researched. Continued research efforts in this important area will result in improved diagnosis and management of pediatric pain. PMID- 2235641 TI - Nausea, vomiting, and retching. AB - Although nausea, vomiting, and retching have plagued mankind since antiquity, limited attention has been given to the three symptoms as separate entities. Although knowledge of symptom occurrence is essential to practice, nurses must focus on patients' response or distress to the occurrence of symptoms. The differentiation of symptom occurrence and symptom distress of nausea, vomiting, and retching is critical to the management and self-care demands of patients and the enhancement of their quality of life. Basic research on patterns of these individual symptoms and their components promises to provide a more progressive and fruitful approach to the patient response to these symptoms. PMID- 2235642 TI - Diarrhea. AB - Diarrhea is one manifestation of GI disturbance. Symptoms may be acute if caused by such things as infections, drug reactions, alterations in diet, heavy metal poisoning, or fecal impaction. Chronic diarrhea is a symptom of GI diseases such as irritable bowel syndrome, lactase deficiency, cancer of the colon, inflammatory bowel disease, and malabsorption diseases. Chronic diarrhea may also be associated with GI surgery, radiation therapy, laxative abuse, alcohol abuse, and chemotherapeutic agents. When interventions are required to deal with diarrhea, they may include such things as alteration in tube feeding products and methods of administration, fluid replacement by oral rehydration procedures, a rapid return to feeding, and education aimed at the health information clients need to prevent or control the symptom of diarrhea. PMID- 2235643 TI - Confusion. AB - The term confusion describes a plethora of possible cognitive deficits and behavioral manifestations. A subjective assessment of confusion must be followed by an objective systematic evaluation to develop the cognitive-behavior profile. Because of age-associated physiologic and pathologic changes, elderly patients are at high risk for developing acute confusion. The management of confusion presents a challenge to nursing. Nursing can play a significant role in the prevention and the early detection of acute confusion. Preventing or identifying confusion early will decrease the physical and psychological stress of the patient as well as decrease the cost of hospitalization by shortening length of stay. Additional research is needed to determine the efficacy of present nursing activities and to identify new approaches for management. PMID- 2235644 TI - Urinary incontinence. AB - Symptoms of urinary incontinence are distressing and disruptive to everyday life. They can also be indicative of more serious underlying disorders. Many methods of symptom management are available. Matching the affected person to the most effective and appropriate treatment method is a significant challenge for nursing. Just as pressing is the need to develop and test a cogent conceptual model for symptom management that includes primary prevention. PMID- 2235645 TI - Stress and anxiety. AB - Anxiety is the psychophysiologic signal that the stress response has been initiated. The stress response's by-product, stress, is difficult to define. The response has multiple dimensions that have yielded research with many foci. Most salient to nursing are investigations of psychobiologic variables, the influence of life events, and the interactional model of the stress response. The stress response can be viewed as an interactional process that causes psychophysiologic reactions that are immediate and can occur up to and including physiologic events 3 weeks after confrontation with the stressor. The literature suggests that neuroendocrine alterations in response to confrontation with a stressor may influence immunocompetence. Intervention and prevention studies of stress focus on pharmacotherapy, psychotherapy, behavioral techniques, personality engineering, relaxation training, and biofeedback. Nursing research on stress has proliferated in the 1980s. Implications for nursing intervention include coping strategies that fall into four categories: behavioral, physical, cognitive, and emotional. PMID- 2235646 TI - Psychologic and physiologic aspects of depression. AB - Depression is a serious condition that will be encountered by most nurses regardless of their specialty area or practice setting. There is good empirical support for biologic and psychologic models of depression. This article discusses how symptom management is enhanced through a combination of psychotherapeutic and somatic treatments. PMID- 2235647 TI - Dyspnea. AB - A multidimensional model of dyspnea that includes sensation, perception, distress, response, and reporting components is presented. Assessment tools currently available are evaluated as are recent research findings for pharmacologic, oxygen, physical, and psychologic treatments. This article concludes by suggesting a role for the nurse in dyspnea amelioration. PMID- 2235648 TI - Fatigue. AB - Fatigue is a pervasive, protective phenomenon affecting the totality of the individual. Assessment and management involve a wide range of activities to address the total human being's physical, psychological, cognitive, and spiritual dimensions. When elimination or neutralization of the effect of an antecedent condition is not an option, redesigning one's life-style may be the primary avenue of fatigue management. This protective mechanism, fatigue, may in fact herald the return of quality and purpose to one's life. PMID- 2235649 TI - Shivering. A clinical nursing problem. AB - Shivering is a common but complex phenomenon that occurs in many patient care situations. Its metabolic costs and cardiorespiratory consequences should not be underestimated, particularly for the seriously ill, debilitated, or elderly patient. Using a conceptual frame of reference for assessment and action, independent and collaborative actions can be planned to reduce the energy expenditure, distress, and loss of control imposed by severe shivering. PMID- 2235650 TI - Nurse, are you a healer? AB - The concept of "nurse as healer" is in itself vague and illusive. It is, however, a concept that is beginning to emerge in practice and in the literature. To begin to develop an understanding of "nurse as healer", the following questions are addressed: Are nurses identified as healers in the nursing literature? In today's world of nursing practice, do nurses consider themselves to be healers? What healing practices do nurses engage in? PMID- 2235651 TI - Nursing students with learning disabilities: guidelines for fostering success. AB - Learning disabilities can be devastating for the nursing student, interfering with academic performance and with success on the NCLEX-RN. Within the past five to ten years, college educators are seeing an increasing number of students with learning disabilities diagnosed in the 1970s, who are now ready for higher education. This phenomenon is becoming apparent as well in schools of nursing in the United States. This article describes the problem, gives characteristics by which the student with a learning disability can be identified, and suggests methods for assisting the student to achieve success in school and on the national licensing examination following graduation. PMID- 2235652 TI - The role of nursing in the influenza epidemic of 1918-1919. AB - Just as the horrors of World War I were winding down, millions of people were stricken by an influenza epidemic that displaced war as the tragic focus of everyday life. The disease was known as the Spanish influenza and was pandemic in scope. Since the epidemic defied the capabilities of prevailing medicine, good nursing care was the best predictor of outcome. Nurses came to the rescue by working long, hard and tirelessly. One important outcome of the epidemic was a general recognition of the visiting nurse service and all nursing as a valuable and essential community service. PMID- 2235654 TI - The "martial law" theory of nursing. PMID- 2235653 TI - Sophomore high school students' perceptions of ideal and nursing career choices. AB - To increase the number of practicing nurses, high school students must be attracted to nursing as a career. This study compares sophomore high school students' perceptions of an ideal career with their perceptions of nursing as a career. Differences are identified and potential recruitment solutions suggested. PMID- 2235655 TI - Concept analysis of decision making. AB - Concept analysis allows us to examine the attributes and characteristics of a concept. The concept of decision making is central to the practice of nursing. Decision making occurs at all levels of human thought and action, so it has been explored in many disciplines. It is important to explore this concept from the perspective of the discipline of nursing, so that we can determine how definitions and theories apply to our practice. Investigating a concept adopted from other disciplines will eventually provide the profession with a basis for knowledge development. PMID- 2235656 TI - [Round-table: fetal echocardiography and ethical problems]. PMID- 2235657 TI - [How and why is the diagnostic approach to celiac disease changing]. AB - The first classic description of celiac disease (CD) was published in 1888. The introduction in the clinical practice of the jejunal biopsy, in 1957, offered a powerful tool for a more objective approach to the disease. The correct diagnostic procedure for CD was finally established by a document of the European Society for Pediatric Gastro-enterology and Nutrition (ESPGAN) in 1970, and the ESPGAN suggestions were rapidly adopted by the scientific community. During these years, alternative and non-invasive diagnostic approaches were developed such as non-immunological (tests of intestinal absorption and permeability) and immunological (anti-reticulin, anti-endomysium and anti-gliadin antibodies, HLA antigens) tests. Due to the increased reliability of some of these laboratory investigations and to the increased knowledge about CD, it has been recently proposed that a simplification of the usual ESPGAN protocol should be eventually adopted in well defined subjects suspected to have CD. PMID- 2235658 TI - [Phagocytic function of PMN granulocytes in a pediatric population with recurrent respiratory infections]. AB - We have studied the Phagocytosis at 32 children who had recurrent respiratory tract infection (RRI). We used a easy method (Phagolux). The seventy-five percent (24/32) of children had a Phagocytosis and/or Opsonisation Deficit during or following the acute respiratory tract infection. All children (except for one who had a C3-deficit) reached normal parameters after (or al least) fourty-five days. PMID- 2235659 TI - [Cardiac involvement in food allergy. Study of cardiac activity by Holter monitoring in 12 allergic children during food challenge]. AB - The authors have based their study on recent research of cardiac anaphylaxis in vitro and studied the cardiac involvement in vivo, by Holter trace in a group of 12 children with food allergy in basal period (food allergens exclusion) and during food allergens reintroduction. In the same time the involvement of respiratory apparatus was followed by RAW's insp.esp. study. The results showed contemporaneously at the RAW's rise a mean increase of cardiac frequency of slight moment when the frequency was computed during 24 h, but evident in challenge phase. The cardiac frequency study in "late" phase of reply at the food allergens challenge showed a heavy and significant increase of cardiac frequency and extrasystole. PMID- 2235660 TI - [Validity and limitations of respiratory physiotherapy in children]. PMID- 2235661 TI - [Thrombopenic purpura following measles vaccination]. AB - A case of acute thrombocytopenic purpura complicating live measles vaccination is reported. Clinically and morphologically this case is identical to the postinfectious thrombocytopenic purpura. An immunological mechanism has been postulated to explain the thrombocytopenia. PMID- 2235662 TI - [Guillain-Barre syndrome in childhood: epidemiology and clinical aspects]. AB - From 1980 to 1988, 25 cases of S.G.B. were diagnosed in children of ages between 2 and 12 years old at the Pediatric Clinic of Catania University. No seasonal or sexual prevalence was observed and only 5 children were less than 5 years old at the beginning of the disease. The diagnosis was based on 2 principal points: 1) pain at the inferior limbs with motor, sensitive and autonomous disturbances; 2) an increase of the globulins in the cerebrospinal liquid without a quantitative variation of the cells. The disease had a medium length of duration of 20 to 30 days; only in 2 children respiratory assistance was necessary, because of an ascending paresis, which included the respiratory muscles, while in 2 other aged 11 and 12 years old the disease presented itself as being diphasic with a short intermittent intervals, which made us think of a complete remission. In one of these 2 patients, the disease manifested itself in an unusual manner, hitting initially the muscles of the upper limbs, the III cranial nerve and with marked cephalgia. The E.M.G. taken on 7 children presented itself as being frankly neuropathic. PMID- 2235663 TI - [Clinical efficacy of sodium diclofenac in chronic juvenile polyarthritis]. AB - We refer the results of an open non-comparative study aimed to evaluate the clinical efficacy of Diclofenac sodium in the treatment of Polyarticular Juvenile Chronic Arthritis. We decided to use this drug to investigate if it exerts also in younger patients the anti-inflammatory and analgesic effects known in adults. We treated 26 patients (14 girls and 12 boys) aged 2-16 years; the disease duration ranged between 3 months and 14 years. Treatment was started only if previous anti-inflammatory drugs had been considered ineffective after a prolonged use (3-12 months). None was on basic therapy. No wash-out period was used for ethical reasons. During the trial period other additional symptomatic or anti-inflammatory drugs were not used. Diclofenac sodium was given by tablets and/or suppositories at the mean daily dosage of 2.4 mg/kg (min. 0.3-max. 5, according to disease activity) for a period of 2-52 months. Diclofenac sodium was particularly effective on joint pain and morning stiffness but also on joint swelling, and functional capacity. We noticed a tendency of JRA to improve during the trial period. The drug was well tolerated; one patient stopped because of headache, another continued the treatment only per os because of intolerance of rectal administration. PMID- 2235664 TI - [Dominant polycystic kidney disease in children. Clinical aspects related to age and problems of early diagnosis]. AB - Two cases of Dominant Polycystic Kidney Disease (DPKD) are reported in newborns of two different affected families. One of two infants was prenatally diagnosed by ultrasound, few cases of in utero diagnosis being previously reported. The two infants had different course: one had no symptoms (14 months now), on the contrary the other one had abdominal mass at birth and oliguria in the first 48 hours, then acute pyelonephritis at 15 months. The increasing incidence of DPKD diagnosed in infants and children by US screening in risk subjects is stressed and importance of precocious diagnosis for genetic counselling emphasized. PMID- 2235665 TI - [Primary intestinal lymphangiectasis. A case treated surgically]. AB - The authors describe a rare case of primary intestinal lymphangiectasis resolved with surgical treatment. Usually the natural course of the disease is relatively mild and medical nutritional treatment can be sufficient. In this case the lymphatic intestinal anomaly was generalized to the entire small intestine but a distal ileal segment was particularly involved. The surgical resection of this intestinal tract resolved the symptomatology. PMID- 2235666 TI - [Sympathetic reflex dystrophy. Description of a pediatric case]. AB - Reflex sympathetic dystrophy is a well known syndrome in adults, but often misdiagnosed in children. We describe a case occurred in a 12 years old girl. Psychological factors played a major role in the mechanism of the disease. Early recognition and prompt management allow complete recovery without sequelae. PMID- 2235667 TI - [Extrapyramidal syndrome caused by moderate overdosage of domperidone. Description of a case]. AB - Domperidone is useful in the treatment of vomiting and gastroesophageal reflux in children. Its efficaciousness is due to the antagonist effect on gastrointestinal dopaminergic receptors. Contrary to the initial expectations, domperidone is able to penetrate into the hematoencephalic barrier and to cause adverse neurologic reactions. We report a case of extrapyramidal reaction in a child after moderate overdosage of domperidone. PMID- 2235668 TI - Pharmacokinetics and pharmacodynamics of anticancer agents: contributions to the therapy of childhood cancer. AB - Strategies for treating pediatric malignancies have not only been successful (i.e., curative) for several disseminated childhood cancers, they have also served as paradigms for the therapy of many adult cancers. Initial strategies included combined treatment modalities (chemotherapy, surgery, radiotherapy) and combinations of different pharmacologic classes of anticancer drugs given in the appropriate schedules. Despite the currently successful therapy for some malignancies (e.g., 70% 4-year disease-free survival in acute lymphocytic leukemia), many children die without known reason. Recent advances in the clinical pharmacology of anticancer drugs have identified relationships between dose intensity and response (efficacy, toxicity). Traditional methods of measuring dose intensity (prescribed dose) have evolved to more sophisticated approaches in maximizing the intensity of treatment, with good response rates. Other methods of optimizing chemotherapy for individual patients include bone marrow support procedures and therapy with biologic response modifiers. Relatively few clinically useful new anticancer drugs have been discovered in the past several years. Fortunately, the potential to improve therapy with currently available agents has come about through enhanced knowledge of the biochemical and clinical pharmacology of anticancer drugs and biologic response modifiers, as well as improved understanding drug resistance biology. PMID- 2235669 TI - Renal dysfunction associated with ciprofloxacin. AB - We cared for a 64-year-old woman who experienced increased serum creatinine levels after 8 days of ciprofloxacin therapy. She had previously received a course of several antibiotics, including gentamicin. Renal function returned to normal 18 days after the ciprofloxacin was discontinued. This is the eighth reported case of nephrotoxicity associated with this agent. The mechanism and predisposing factors have not been defined. PMID- 2235670 TI - Prospective surveillance of intravenous amphotericin B use patterns. AB - Information on amphotericin B use patterns and infusion-related adverse events were prospectively collected from 397 hospitalized adults. The methods of initiating amphotericin B varied greatly, with the majority of patients being gradually titrated to a full maintenance dose over 1-5 days. Overall, 71% of patients experienced at least one episode of an infusion-related adverse event (IRAE) during the first week of therapy. Fever and chills were most commonly observed, with peak frequency on days 1-3, followed by a subsequent decline. A wide variety of pretreatment medications were used to minimize IRAE; the most common regimens included some combination of diphenhydramine, acetaminophen, and corticosteroids, with or without heparin. The majority of patients (84.7%) received a test dose, and although none experienced a severe allergic reaction, one patient subsequently had an anaphylactic episode on the third day of amphotericin B therapy. The use of a test dose and the titration process are attempts to avoid the IRAE frequency associated with large initial doses of amphotericin B, but we observed that they provided little or no benefit. In addition, our study suggests that pretreatment regimens are frequently used in conjunction with the test dose. If the intent of the test dose is to identify patients sensitive to amphotericin B, pretreatment drugs may minimize these adverse events and prevent a complete evaluation of response to the test dose. PMID- 2235671 TI - Pharmacokinetics and pharmacodynamics of heparin during hemodialysis: interpatient and intrapatient variability. AB - Heparin pharmacokinetics and pharmacodynamics were studied in 17 patients undergoing hemodialysis, once a week for 4 weeks in order to evaluate intrapatient variability over time. A single bolus injection of heparin was administered directly into the circulation immediately prior to the start of hemodialysis in doses ranging from 3000 to 12,000 U. Blood samples were obtained to determine activated coagulation times (ACT) and heparin concentrations (HC). Combined zero- and first-order elimination was seen in each of the 4 weeks. The half-life of heparin decreased from beginning to end of hemodialysis during each week, with the percentage of decrease from the start of dialysis ranging from 70 74%, indicating concentration-dependent elimination. Since the zero-order component did not appear to be clinically significant, first-order elimination was assumed. A linear decline in ACT over the time of the dialysis period was also seen during each week. A profile of ACT versus HC was generated for each patient as well as for the mean data to assess the relationship of HC to response. An excellent correlation was found for both individual patient data and mean data. In the third week the patients were randomized to receive standard treatment or an individualized dose. They were then crossed over to the opposite group in the fourth week to see if this relationship between ACT and HC would be useful in predicting heparin dose. These profiles were used to individualize the dose during either the third or fourth week of the study. No significant differences were noted between actual and predicted ACT. A significant degree of interpatient variability was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235672 TI - Effect of glycated albumin on phenytoin binding in elderly patients with type II diabetes mellitus. AB - We evaluated the effect of glycated albumin on phenytoin protein binding in 36 elderly (age range 63-94 yrs) patients with type II diabetes mellitus (DM) under diet management. Serum was spiked with 15 mg/L phenytoin and incubated. A serum ultrafiltrate was obtained from each sample for determining total and free phenytoin concentrations. Glycated hemoglobin was determined by boronate-affinity chromatography, and glycated albumin was separated from nonglycated fractions with boronate-agarose gel. Glycated hemoglobin in the study group ranged from 4.3 14.6% (mean 7.8 +/- SD 2.1%) and glycated albumin ranged from 3.7-12.5% (7.4 +/- SD 2.6%). We observed no correlation between glycated albumin and the percentage of free phenytoin (r2 = -0.14; p = 0.419). The concentration of nonglycated albumin ranged from 0.66-4.28 g/dl (mean 3.45 +/- 0.67 g/dl) and was calculated from measured total and glycated albumin concentrations. A correlation between the free fraction of phenytoin and nonglycated albumin was not demonstrated (r2 = 0.22, p = 0.22). In addition, a correlation was not observed between total glycated albumin and the free fraction of phenytoin (r2 = -0.095; p = 0.58). We conclude that elderly patients with type II DM under diet control do not have significant alterations in phenytoin protein binding. The use of total serum phenytoin levels therefore appears appropriate for determining phenytoin dosages in elderly patients with well controlled type II DM. PMID- 2235673 TI - The osteogenic stimulating effect of neuroactive calcitonin gene-related peptide. AB - Silverman and Kruger (Somatosens. Res. 5(2):157-175; 1987) reported that sensory nerve fibers of the dental pulp secrete calcitonin gene-related peptide (CGRP). These are localized exactly where secondary or tertiary dentin calcification occurs. Recently we found that CGRP has an osteogenic stimulating effect by increasing the number and size of bone colonies in vitro. The purpose of this study is to test whether there is a relationship between the effects of different doses of CGRP and bone colony numbers and/or size. Rat CGRP in different dosages (0.4, 4 and 40 micrograms/ml in BGJb medium) was added daily to 3 million light density (LD) bone marrow white cells which were harvested from adult Sprague Dawley rats with the Ficoll-Paque density gradient separation method, then seeded onto a previously prepared feeder layer of fibroblasts in Petri dishes. Seven days after adding CGRP, in the controls without CGRP there were 2 bone colonies; with 0.4 microgram of CGRP there were 4 colonies; with 4 micrograms of CGRP there were 6 colonies; with 40 micrograms there were 9 colonies, indicating there was a significant increase in number of bone colonies with an increase in dose of CGRP between individual groups, respectively (p less than 0.0005 and p less than 0.0001). In another experiment, intravenous injection of 10 micrograms of rCGRP/kg body weight was performed two hours before surgery. LD bone marrow white cells were collected and seeded onto a feeder layer in Petri dishes exactly as described above.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235674 TI - Cysteinyl methyl ester of AVP(4-8), a potent agonist on the maintenance of passive avoidance in rats. AB - A series of short AVP analogs with D- or L-arginine forming the C-terminal was synthesized, and their peripheral effects, i.e., vasoconstrictor and antidiuretic activities, and behavioral effects in enhancing retention in passive avoidance in rats were evaluated. We found that: 1) AVP(4-8) and its cysteinyl methyl ester were more potent in the behavioral response than its D-Arg homologs; 2) the methyl ester derivative was the most effective analog in this behavioral test among the peptides we synthesized, with a potency 40 times as high as AVP; 3) neither the D- nor the L-Arg short derivatives of AVP showed any peripheral effects up to a dose thousands of times greater than AVP. The results support the contention that arginine in the short analogs plays an important role in their behavioral response associated with a relatively steady peptide conformation. PMID- 2235675 TI - Effect of avian neurotensin on motility of chicken (Gallus domesticus) lower gut in vivo and in vitro. AB - Mammalian neurotensin, originally isolated from bovine hypothalamus, differs from avian neurotensin (aNT) by 6 amino acid residues. Bovine neurotensin has been shown to affect motility of chicken crop and rectum and secretion of chicken ileum, but there have been no studies of the effects of aNT on avian intestinal function. This study was designed to characterize the effects of aNT on the motility of the chicken lower gut. Strain gauge transducers were used in vivo to measure contractions of chicken distal ileum, cecum, and distal colon in response to 30-min infusions of aNT at rates of 15, 30, 60 or 600 pmol.kg-1.min-1. In vitro experiments were conducted using segments of distal ileum, cecum or distal colon, stripped of mucosa, cut in either the longitudinal or circular plane, and suspended isometrically in isolated organ tissue baths at a resting tension of 1 g. Avian neurotensin, substance P (SP), or carbamylcholine (CCH) were administered to the bath and the tension generated by each tissue was recorded via a force transducer. A relaxation of chicken ileum was observed in response to aNT infusion in vivo. Except for stimulation of excretation, colon and cecum were not affected by aNT infusion. Both aNT and SP stimulated motility of chicken ileum and cecum in vitro. SP had no consistent effect on colon and aNT only increased contractile force of colon circular muscle. It was concluded that both aNT and SP may have a role in the regulation of lower gut motility in avian species. PMID- 2235676 TI - Salmon pancreatic polypeptide exhibits neuropeptide Y-like activities in rats. AB - Salmon pancreatic polypeptide (sPP) is a 36 residue peptide amide isolated from salmon pancreas. It has 83% sequence identity with porcine neuropeptide Y (NPY). To confirm the sequence and obtain sufficient quantity of peptide for biological investigations, sPP was synthesized by automated t-Boc solid phase synthesis. The purified product had the expected amino acid composition, primary structure and mass, and was chemically and biologically indistinguishable from natural sPP. Investigation of its biological properties revealed that, like NPY, sPP increased blood pressure and decreased heart rate in anesthetized rats in a dose-dependent manner. There was no significant difference in the responses of NPY and sPP. Furthermore, administration of sPP directly into the hypothalamus of rats induced a feeding response comparable to that induced by NPY. Based on these investigations it may be suggested that synthetic and natural sPP are identical, and that sPP can express NPY-like activities in mammals presumably by interacting with the receptors of NPY. PMID- 2235677 TI - Synthetic domains of cystatins linked to enkephalins are novel inhibitors of brain cathepsins L/B. AB - Cystatin domains or homologous sequences were synthesized and tested as inhibitors of papain, and rat brain cathepsins B and L. These domains included: I, an enzyme substrate binding site containing a -GG- cleavage site (YGGFL); II, known cystatin consensus sequences (-QVVAG- or -QLVSG-); and III, the proposed ancillary site for binding of chicken cystatin to papain (-IPWLN-). A Domain II analog QVVAG(K-NH2) inhibited cathepsin L and papain with Ki 1-4 X 10(-4) M but was inactive towards cathepsin B. A peptide containing Domains I and II, YGGFL QVVAG(K-NH2), inhibited papain and cathepsin B with Ki 10(-4)-10(-5) M, and cathepsin L with Ki 10(-6) M. The presence of Domain III in the analog YGGFL QVVAG-IPWLN(K-NH2) resulted in a 10-fold increase in potency towards papain. These data demonstrated that putative cystatin domains are: 1) probably proximal in the intact cystatins; 2) can be linked directly to each other to yield smaller peptides active as inhibitors; 3) showed some specificity towards the three cysteine proteinases. PMID- 2235678 TI - Purification of peptide hormones from chinchilla pancreas by chemical assay. AB - Glucagon was purified from chinchilla pancreas and its biological activity determined. It was isolated using a chemical assay to identify peptides with a histidyl residue at the N-terminus. Chinchilla glucagon has the amino acid sequence HSQGTFTSDYSKHLDSRYAQEFVQWLMNT. It differs from the usual mammalian glucagon by amino acid substitutions at positions 13, 18 and 21 from the N terminus. Despite these sequence changes, its biological activity is conserved. Chinchilla glucagon has approximately the same potency as pig glucagon in stimulating liver membrane adenyl cyclase activity. Pancreatic polypeptide was also purified from chinchilla pancreas based on its Ala1 signal and has the sequence APLEPVYPGDNATPEQMAQYAAEMRRYINMLTRPRY#. PMID- 2235679 TI - Enkephalins interfere with early phases of voluntary ethanol drinking. AB - The relationship between the opiate peptides Leu-enkephalin and [D-Ala2 Met5]enkephalinamide (DAME) and the initial expression and maintenance of ethanol preference was studied in male Wistar rats. Subcutaneous administration of both peptides prior to the first choice test between water and ethanol induced reductions on ethanol intake and subsequently on total fluid intake. Leu enkephalin treatment also diminished ethanol preference in the day of treatment and in consecutive days. Neither Leu-enkephalin nor DAME treatments modified rats sucrose preference or intake. The results suggest that the enkephalins studied, when administered in the early phases of ethanol preference, interfere with the mechanisms involved in the propensity to drink ethanol. PMID- 2235680 TI - Isolation and primary structure of VIP from sheep brain. AB - The amino acid sequence of the vasoactive intestinal polypeptide (VIP) is well conserved between species. Thus, all mammalian VIPs isolated so far, except that of the guinea pig, have the same amino acid sequence. This study describes the isolation and primary structure of sheep brain VIP. The purification was followed with a bioassay and a VIP receptor assay. The amino acid sequence of the isolated sheep VIP is identical to that of the pig, human, ox, rat, rabbit, goat and dog VIP. PMID- 2235681 TI - Isolation and sequence of canine xenopsin and an extended fragment from its precursor. AB - Canine xenopsin and a 27 residue segment of its precursor immediately surrounding the xenopsin moiety were isolated from acidic extracts of stomach. The six C terminal residues of canine xenopsin, H-Phe-His-Pro-Lys-Arg-Pro-Trp-Ile-Leu-OH, were identical to those in Xenopus xenopsin less than Glu-Gly-Lys-Arg-Pro-Trp-Ile Leu-OH. The amino acid sequence determined for the segment of the precursor was similar to the corresponding region of Xenopus pro-xenopsin (approximately 33% homology) and to the related Xenopus precursors, pro-levitide, pro-PGLa, pro magainin and pro-caerulein. These results, indicating evolutionary conservation of xenopsin and a portion of its precursor, suggest that this peptide has important biologic function(s). PMID- 2235682 TI - Endothelin-1 acutely stimulates the secretory activity of rat zona glomerulosa cells. AB - A bolus IV injection of endothelin-1 (ET-1) (0.5 microgram.kg-1) decreased PRA, without affecting plasma aldosterone (A) concentration. ET-1 exerted a dose dependent stimulation of basal secretion of A and corticosterone (B) by dispersed zona glomerulosa (ZG) cells, while it did not affect B production by inner adrenocortical cells. ET-1 notably enhanced the secretory response of dispersed ZG cells to a maximal effective concentration of ACTH, but not of either angiotensin II (ANG-II) or potassium. The conclusion is drawn that ET-1 acutely stimulates ZG in rats, by a mechanism probably similar to that underlying the adrenoglomerulotropic actions of ANG-II and potassium. PMID- 2235683 TI - Further observations on the mechanism of the cardiovascular reflexes caused by exposure of the peritoneum to neurotensin. AB - Intraperitoneal (IP) injections of either 1, 3 or 9 ml of neurotensin-containing solutions (NTCS) with 5.4, 54, 540 or 5400 nM of neurotensin (NT) were found to cause concentration-dependent, but volume-independent, increases of blood pressure (BP) and heart rate (HR) in anesthetized, close-abdomen guinea pigs. The duration of both effects varied between 15 to 30 min depending both on the NT concentration and volume of NTCS utilized. Indirect evidence suggested that NT inactivation within the peritoneal cavity contributed to shorten the duration of NT effects. Animal pretreatment with a ganglion blocker, adrenoceptor antagonists, clonidine or capsaicin, reduced the BP and HR increases caused by IP injection of NTCS whereas both effects were either unaffected or slightly potentiated by animal pretreatment with atropine, morphine or captopril. Addition of a local anesthetic to NTCS inhibited the hemodynamic effects of NT whereas acute bilateral cervical vagotomy was without significant effect. These results suggest that NT has the ability to trigger cardiovascular reflexes following its IP injection in guinea pigs. The activation of peritoneal, sympathetic, capsaicin sensitive primary afferents appears to be at the basis of these reflexes, the amplitudes of which seem poorly related to the volume of NTCS utilized (at least within the range of volume examined). PMID- 2235684 TI - A new peptide in the FMRFamide family isolated from the CNS of the hawkmoth, Manduca sexta. AB - We have purified a FMRFamide-like peptide from extracts of brain-subesophageal ganglion of the moth, Manduca sexta. The purification was monitored with a new, competitive ELISA, and accomplished with ion exchange and reverse-phase HPLC. The peptide structure was determined by a combination of tandem mass spectrometry and automated Edman degradation. The amino acid sequence of the peptide is less than Glu-Asp-Val-Val-His-Ser-Phe-Leu-Arg-Phe-amide (pEDVVHSFLRF-NH2). In a separate purification, an identical peptide was isolated from extracts of brain-associated neurohemal structures. We have named this peptide ManducaFLRFamide, to indicate its homology with other members of the "FMRFamide" family. In bioassays, chemically synthesized peptide increased the force of neurally evoked contractions in the major power-producing flight muscles, the dorsal longitudinal muscles. This observation suggests that hormonally released ManducaFLRFamide may play a role in sustaining or promoting the flight behavior necessary for mate seeking (in males) or oviposition (in females) in sphingid moths. PMID- 2235685 TI - Peptidergic innervation of the major salivary glands of the ferret. AB - In parotid, sublingual and submandibular glands of the ferret, morphological correlates were looked for, using immunocytochemistry, to previous physiological findings showing parasympathetic "atropine-resistant" salivary secretion and neuropeptide-evoked salivation in this species. Nerve fibers storing VIP were numerous in association with acini, ducts and blood vessels, while the number of fibers storing substance P was moderate and those containing CGRP and galanin few; also the number of NPY-containing fibers was low around acini and ducts but relatively high around vessels. Sympathectomy eliminated all NPY- and almost all dopamine beta-hydroxylase-containing fibers. Parasympathectomy of the parotid gland resulted in a total loss of the VIP-containing fibers, and a profound reduction in the number of substance P- and CGRP-containing fibers. PMID- 2235687 TI - Adolescence: psychopathology, normality, and creativity. PMID- 2235686 TI - Somatostatin inhibits neutrophil elastase release in vitro. AB - The influence of the long-acting somatostatin analogue, SMS 201-995, on FMLP induced neutrophil elastase release in vitro has been investigated. Doses from 150 ng/ml upwards inhibited elastase release, with 100% inhibition by 2500 ng/ml. Inhibition was demonstrated both by an assay measuring elastase immunometrically and by an assay based on its enzyme activity. The demonstration that SMS 201-995 inhibits protease release from polymorphonuclear leukocytes may have implications for the long-term clinical use of this somatostatin analogue. PMID- 2235688 TI - Normality and adolescence. AB - Diagnostic work with adolescents has always been difficult. The problem is to distinguish serious psychopathology from mild crisis. We can now say, however, that a severe identity crisis and emotional turmoil are just not part of normal growing up. Our belief is that we do not help adolescents who experience such crises or turmoil when we tell them not to worry about their problems because they are a normal part of adolescence and because they will "grow out of it." In summary, we have presented data on the self-image of a large number of adolescents. We have stressed three things. First, we used self-administered questionnaires to collect our data. Most important, our data are consistent, and they are congruent with results obtained from use of other psychologic instruments such as interviews or parents' evaluations of their children. Second, we found that the normal groups of adolescents we studied were characterized more by their similarities than by their differences. The continuity of values for all our samples over an 18-year period and across cultures was especially impressive. Third, we stressed the diversity of adolescents' view of their psychologic worlds. These youths define normal functioning and development. They reside in our communities, and before we can help their disturbed peers who need professional help, we need to know what the norm is. Only then can we correctly diagnose and successfully treat the adolescents who do seek our help. PMID- 2235689 TI - Personality status: changes through adolescence. AB - 1. Forty-two percent of a nonclinical sample of urban 18 year olds displayed some degree of personality dysfunction. This rate of disturbance is similar to a previously reported rate for 13 year olds, but higher than the prevalence rate for 16 year olds. Thus, early and late adolescence seem to represent "at risk periods" for the genesis of character pathology. 2. In late adolescence, the form of this disturbance is as follows: 40% fall into a histrionic, borderline, narcissistic cluster, whereas nearly 30% demonstrate an atypical or mixed picture. This differs markedly from the distribution of dysfunction in earlier subphases. 3. Thirty-eight percent of the disturbed sample showed evidence of dysfunction at all three subphases (early, middle, and late), whereas 62% fluctuated in or out of disturbance at one subphase or another. 4. There was a notable lack of consistency with respect to type of personality dysfunction from both a group and individual perspective, except for paranoid, schizoid, and schizotypal disturbance. This particular cluster retained both group and individual stability from age 13 to 18. 5. Two trends were evident however: teenagers who initially presented as avoidant, dependent, compulsive, or passive aggressive seemed to grow out of their dysfunction. By age 18, hardly any of the original subjects remained in this cluster, and most had become clear. Secondly, most of the adolescents identified as antisocial in early or middle adolescence migrated into the histrionic, narcissistic, borderline cluster in late adolescence. This latter group showed a steady increase throughout the time span studied, suggesting the importance of developmental factors. PMID- 2235690 TI - Psychosis and adolescence. The relation of intrapsychic structure formation and change to action and task. AB - This article is an exploration of intrapsychic structure formation and change from the point of view of a psychoanalytic concept of action. It compares the normal development of intrapsychic structure with that involved in psychotic disorganization as individuals encounter adolescence and its developmental tasks and requirements for action. The flexible complexity of intrapsychic structure and available action in a normally developing adolescent and the contrasting fixed simplicity of intrapsychic structure and its repertory of action in psychotic patients are highlighted. Four different environmental life occasions, all of which are associated with intrapsychic change, are examined against this background. The first of these involves little initial action on the part of the ego, although lasting change does occur. The last three involve both inner and outer developmental actions that can be central to growth and may be the occasion of psychosis. The first environmental life occasion is "trauma," in which the person's action, potentialities, and intrapsychic structure are disrupted by the world's destructive action and are thereby changed. The second is "intimacy," in which newly evolved actions and interaction are sought, often with little regard for or knowledge of the accompanying necessities of intrapsychic change. In the third --"success"--new intrapsychic change and altered necessities of action can surprisingly affect both the sense of continuity within one's inner world and the nature of one's relationship to the action of the outer world. The fourth occasion is "analytic" therapy, in which the regularities of one's intrapsychic structure and its stereotypies of action are often disrupted by the very "therapeutic" processes that allow these to be observed and examined in the course of promoting progressive development. All of these exciting and dangerous occasions mark out a separate, autonomous, individual, chosen act. The attempt to explicate the role of action in intrapsychic structural change during analytic work with a psychotic patient defines the analyst's actions as interferences and disruptions of that inner structure. His actions are noted, felt, represented, and organized into a part of that reformed, newly organized inner structure. Those analytic actions are represented by the patient as "having an impact" upon the patient and do indeed affect the patient. In that regard it is asserted that for a full, psychoanalytic conception of the ego, what is required is not only a central "body ego," but the integration of action in the formation and function of that ego's intrapsychic structure--an "action ego." Clarification of the complex relationship of conceptions of "fantasy" and action are re-examined in this context.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2235691 TI - Creativity in adolescence. AB - Findings from an empirical research project on creativity, including controlled experimental assessment, indicate that the development of creative capacity occurs primarily during the adolescent period. Defined as the production of entities that are both new and valuable, creativity necessarily involves two specific types of cognition designated as the janusian and homospatial processes. Although there are precursors to the development of creativity during earlier childhood, both the motivation and the capacity to create appear first in the adolescent period. Important motivational factors derive from adolescent conflicts and developmental tasks such as the impetus to solve and consolidate issues relating to identity, the return of oedipal conflicts, and the pressures toward autonomy and independence. Engaging in creative types of fields and outlets helps generally to establish coherent identity during adolescence and beyond; the beginnings of a specific creative identity in adolescence are a necessary foundation for creative motivation and ability to create throughout life. The return of the oedipal conflict at the onset of puberty motivates the dual compliance and competition of the creatively disposed adolescent with his or her same-sex parent. The pressures toward autonomy and independence provide the motivational and affective substrate for the development of the homospatial and janusian processes. The homospatial process arises from the vacillating and concomitant experiences of autonomy (or separation) and connectedness. In the creatively disposed adolescent, one who activates and uses cognition to express and explore affect, the creative aspect of those experiences begins to be manifested in the concomitant cognitive separation and connection involved in superimposition of mental images. The janusian process arises from the experiences of rebellious oppositionality and intense emotional ambivalence. The creative cognitive aspect of these experiences is manifested in conscious conceptualization and use of simultaneous antitheses and oppositions. The use of simultaneous opposition in the janusian process at any age necessarily involves the capacity to grasp and manipulate abstract relations. Evidence for the first development of this capacity in adolescence comes from the research on formal operations reasoning and on understanding of the null class. Regarding the onset near that age period of capacity to use and comprehend the relational nature of opposition, supporting evidence derives from experimental data on the syntagmatic paradigmatic shift. With regard to the homospatial process, which is largely responsible for the creation of effective metaphors, both the late appearance of class inclusion behavior and the inability of younger children to comprehend and use relational metaphors preclude a preadolescent onset of this creative capacity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2235692 TI - The drug abusing adolescent: clinical issues. AB - Clinical intervention with adolescent substance abusers is a complex issue. Disputes remain regarding the precise nature of the disorder. Treatment of the adolescent is complicated by the normal development tasks of this age, particularly denial of possible consequences and adoption of attendant risk taking behaviors. Treatment begins with a complete drug history and must not neglect the adolescent's family and other support system. The mental health professional, especially the psychiatrist, can make a unique contribution in this area, despite the "bad press" he has so often received by the rest of the (treatment) community. PMID- 2235693 TI - Feeling states during adolescence. AB - Adolescence is characterized by a wide variety of feeling states with certain stages in adolescence being associated with particularly strong affects, a result of the normative developmental process. Affective psychopathology during the adolescent years, particularly in the disorders of depression and mania/hypomania, is characterized by abnormalities in the quality and quantity of affective patterns and additionally by the appearance of feeling states, which may be historically uncharacteristic for the teen (i.e., out of keeping with his previous longitudinal pattern of personality development). Clinicians faced with assessing disturbances in feeling states during the adolescent years must carefully distinguish fluctuating developmental problems from clinical syndromes. A longitudinal assessment period is usually necessary before this distinction can be made with some certainty. The prescription of treatment, be it psychologic, biologic, or systems based, should await the completion of a careful clinical assessment prior to its institution. PMID- 2235694 TI - Adolescent problem behaviors: the influence of attachment and autonomy. AB - This article reviews current literature on adolescent problem behaviors and suggests that a model based on attachment theory and theories of adolescent autonomy and relatedness can help explain the development of these behaviors. When adolescents hold models of relationships with parents that are characterized by anger and insecurity and face increased pressures to seek autonomy, a high risk of problem behaviors ensues. Treatment implications flowing from this model are discussed. PMID- 2235695 TI - Adolescence and eating disorder: the obsessive-compulsive syndrome. AB - Although it is widely recognized that eating disorders primarily begin during the adolescent period, the centrality of obsessive-compulsive symptomatology and dynamisms and their relationship to adolescent conflict and development has not been generally accepted or understood. Social pressures toward conformity with the ideal of feminine thinness, which are especially influential during the adolescent period, combine with obsessive-compulsive predispositions to produce eating disorder symptoms and patterns of behavior. Obsessive preoccupation with images of food as well as ruminative calorie counting, and ritualistic behavior regarding food, use of laxatives, and vomiting, together with an underlying focus on control, undoing and other obsessive-compulsive defenses, and a sado masochistic orientation to the body all point to an essential obsessive compulsive disorder. The presence of dysphoric affect and the erratic success of antidepressant medication with eating disorder patients has led to a belief in an underlying affective disorder. However, careful assessment of eleven studies presenting differential diagnostic data regarding anorexia nervosa reveals that noneating related obsessive-compulsive patterns and symptoms are second overall in incidence to depressive patterns and symptoms. With critical re-evaluation of data presented, the obsessive-compulsive condition equals or supersedes the depressive one in many samples. Moreover, given the intense achievement orientation of persons with obsessive-compulsive illness, along with other psychodynamic factors, depressive symptoms could well be considered a secondary breakdown effect. If the all-pervasive obsessive-compulsive nature of eating related symptomatology discussed here is taken into consideration, depressive symptoms must be considered either secondary or incidental. As patients with eating disorders are notoriously secretive and oftentimes misleading about their symptoms and themselves, a diagnostic assessment of such patients in intensive treatment at a long-term hospital facility was carried out. Compared with a control group randomly selected from the remainder of the hospital patient population, obsessive-compulsive manifestations of rumination, ritualistic behavior, excessive cleanliness, excessive orderliness, perfectionism, miserliness, rigidity, and scrupulousness and self-righteousness were all significantly associated with the eating disorder patient group. The current eating disorder picture, therefore, appears to be a modern form of obsessive compulsive illness beginning during the adolescent period. PMID- 2235697 TI - Youth suicide: risk factors, assessment, and treatment of adolescent and young adult suicidal patients. AB - One of the most difficult clinical problems facing the mental health professional is the prediction and prevention of youth suicide. Suicide is currently the third leading cause of death for young people, ages 15 to 24, in the United States. This article presents several models for understanding youth suicidal behavior including psychologic, sociologic, and biomedical explanations. It summarize what is known about risk factors for adolescent and young adult suicide, including psychiatric diagnosis, personality traits, psychosocial factors, associated medical illnesses, biologic correlates, and family history and genetics. Knowledge about these risk factors will be translated into practical considerations for the treatment of adolescent and young adult suicidal patterns, including psychotherapeutic, psychopharmacologic, and environmental interventions. PMID- 2235696 TI - Paths of adolescent ego development: links with family life and individual adjustment. AB - In broad strokes, we have reviewed family contexts and adjustment of adolescent ego development. We concluded with group portraits, the salient family and individual characteristics of adolescents who followed six paths of ego development. There are strong differences in development--the profound arrests and the dramatic progressions. Although these composite pictures provide us with clearer ideas about each of the paths, we do not yet have a detailed understanding of how adolescents following the varied paths experience the world and relate in their families. Certain questions can only be pursued with this information. For instance, are there ways that parents of the steady conformist adolescents speak and behave that restrain their sons' and daughters' separation from the family? Or do the profoundly arrested teenagers provoke their parents to be less encouraging of their differences from other family members? These questions, touching on complex interactions flowing between parents and adolescents, require a closer look inside the families of teenagers following these paths of arrest and advance. In a work soon to be published, we listen closely to the voices of 13 adolescents and their parents, in solo and while together as a family. These narratives convey the message that paths of individual development are embedded within the intricate matrix of family relationships. The teenagers and their families closely and often poignantly illustrate the ways in which adolescents and parents handle the central dilemma posed during this phase of the life cycle: how to separate from the family and reaffirm one's place within it. PMID- 2235698 TI - Psychopathology, normality, and creativity in adolescence. PMID- 2235699 TI - [Neonatal complications in infants born to mothers with diabetes mellitus]. AB - Health status of 53 babies delivered by diabetic mothers are discussed. Neonatal period was uncomplicated only in 12 cases. The remaining babies suffered from respiratory disorders, edema, neurological disturbances, prolonged jaundice, infections etc. Metabolic disorders in diabetic female are unfavourable for the development of pregnancy and neonate health. it may be improved by the proper diagnostico-therapeutical management prior to and during pregnancy and by intensive care of neonates after delivery. It requires, however, the establishment of health institution with highly qualified teams well equipped which will be able to carry out diagnosis and therapy of diabetes mellitus in females in the reproductive age, during pregnancy as well as proper care of the neonates. PMID- 2235700 TI - [Effects of drugs used in high-risk pregnancy on child development]. AB - The study involved 60 children delivered by the mothers of risk group who were given gestagens and beta-adrenomimetics during pregnancy. Physical, motoric development and morbidity in this group of children with particular relation to respiratory diseases were subject to our study. Thirty eight children delivered by healthy mothers were used as a control group. It was found that there was no developmental abnormalities in children from pregnancies maintained with gestagens and beta-adrenomimetics. Morbidity rate was the same in the tested and control groups. PMID- 2235701 TI - [Blood flow in the umbilical artery in physiological pregnancy]. AB - Fetal umbilical artery flow was measured with Doppler ultrasound technique in 206 cases of the uncomplicated pregnancy. Indices A/B and R.I. were calculated. It was shown that vascular resistance in the umbilical artery is decreasing in the normal pregnancy parallel to its development and is manifested by the changes in A/B and R.I. values. PMID- 2235702 TI - [Symptoms of neonatal abstinence syndrome. Case report]. AB - A case of the neonatal narcotic abuse syndrome is presented. A newborn baby additionally suffered from the congenital infection. Marked symptoms of narcotic withdrawal required an administration of the opiates and tranquillizers for three weeks. PMID- 2235703 TI - ["Munchausen syndrome by proxy" as an example of diagnostic error]. AB - A case of the girl who underwent multiple hospitalizations is presented. Gastrointestinal disorders were seen in the infancy together with skin rash of allergic type, hypoglycaemia without any clear reason in the fourth year of age, and polyuria with hyponatremia and hypokalemia since the sixth year of age. Mother's lack of concern was unexplainable in view of the deteriorating child's health. Samples of the urine and faeces supplied by the mother have shown the laboratory findings suggesting that potassium chloride was added to the faeces and natrium hydrocarbonate--to the urine. Urine collected during polyuria contained large quantities of furosemide. Long-term follow-up, numerous examinations and performed tests have led to the diagnosis of the particular form of the ill-treated child syndrome, so-called "Munchausenn by proxy" syndrome. PMID- 2235704 TI - [2 cases of acute disseminated intravascular coagulation in normal pregnancy and as the first symptom of acute promyelocytic leukemia]. AB - Two cases of the acute disseminated intravascular coagulation (DIC) are presented. DIC in the first case was diagnosed in healthy pregnant woman without any obstetric pathology. This patient recovered completely. The acute DIC in another patient preceded the acute promyelocytic leukemia. The patient died despite a control of DIC. DIC therapy included antifibrinolytic agents and additionally corticoids in pregnant patient. Heparin was not administered because of post partum period and foreseen cytostatic therapy in the leukemic patient. PMID- 2235706 TI - [Arterial hypertension in pregnant women]. PMID- 2235705 TI - [A proposed model of the treatment of diabetes mellitus in pregnancy]. AB - A model of management of pregnant diabetic patients is proposed. Such a model has been implemented at the Voivodeship Out-patient Clinic for Diabetics. Proposed model includes recent data on diabetes mellitus complications and the effect of coexisting diseases on the mother and fetus health. Management was adapted to the real and potential possibilities of health service in Poland. A decrease in the rate of mortality of fetuses under 7% was achieved. It is worth emphasizing despite higher value than those reported in the literature. PMID- 2235707 TI - [Actual views on the classification and results of surgical treatment of lung cancer]. PMID- 2235708 TI - [Clinical picture of secondary pneumonia in our observations]. AB - Hundred sixty four patients with the secondary pneumonia were analysed. The secondary pneumonia amounted to 65.8% of all cases of pneumonia treated within several years. Patients' sex, age, clinical symptoms, X-ray findings, coexisting diseases, sequence of the symptoms and the rate of their disappearance were analysed. It was found that the secondary pneumonia is prevailing in males over 40 years of age and most frequently accompany cardiac failure and chronic unspecific respiratory diseases. It is characterized by slow onset and the lack of typical symptoms in the high percentage of patients. Radiological and clinical symptoms disappear more slowly. However, various ausculatory symptoms of pulmonary involvement often accompany the secondary pneumonia and are not directly related to the inflammatory lesion to the lungs. PMID- 2235709 TI - [Bronchial asthma in hay fever]. AB - The author diagnosed cough, emphysema and the symptoms characteristic for the bronchial asthma in 43% of patients with seasonal allergy (rhinitis, conjunctivitis) to pollens. Such symptoms were more frequent (51% of cases) in patients allergic to the grass pollens with coexisting hypersensitivity to Compositae family. Asthmatic symptoms in patients allergic only to grass pollens were seen in 38%. The author suggests that prolonged exposition in the inhalatory allergens (from two to four-five months) plays an important role in asthma onset in such patients. It rather delays than accelerates admittance to allergic clinics. PMID- 2235710 TI - [Enzymatic reactivity of neutrophils in tobacco smokers]. AB - Activity of 8 enzymes in neutrophils of tobacco smokers was assayed with histochemical semiquantitative technique. An increase in the activity of acid phosphatase and beta-glucuronidase was found in the short period of tobacco smoking lasting 6.5 years on the average. Low activity of beta-glucuronidase, N acetyl-beta-D-glucosaminidase, non-specific alpha-naphtolesterase and LAP was found in the individuals smoking tobacco for 18.5 years. The authors suggest that carcinogenic action of the tobacco smoke is also related to the disorders in neutrophils enzymes activity. PMID- 2235711 TI - [Respiratory insufficiency in patients with myasthenia gravis]. AB - We evaluated 20 patients who required prolonged mechanical ventilation for respiratory failure associated with myasthenia gravis. All 20 patients survived and were weaned from the ventilator after 3 to 14 days (mean 6.5 days) of respiratory support. Progressing bulbar symptoms and respiratory infection were the most frequent causes of the myasthenic crisis. During a period of assisted mechanical ventilation, anticholinesterase medication was interrupted and the patients were treated with steroids and antibiotics. Plasmapheresis may be considered in the management of myasthenic crisis. PMID- 2235712 TI - [Effect of intravenous administration of aminophylline on the degree of saturation of urine with calcium phosphate]. PMID- 2235713 TI - [Use of ceftriaxone in urinary and respiratory tract infections]. AB - Efficiency of ceftriaxone (Rocephin Hoffman Laroche) was assessed in 16 children aged between 3 and 14 years and in 4 adults aged between 17 and 70 years with severe infections of the urinary and respiratory tracts caused by E. coli. S. pneumoniae, P. aeruginosa, P. mirabilis or enterococci. Pyelonephritis as a sole pathology was diagnosed in 10 patients whereas in further 8 patients it complicated other diseases (nephrotic syndrome, hepatitis, cholangitis, leukemia). Pneumonia complicated nephritis leukemia or lymphoma in 8 children. Peritonitis was diagnosed in 1 adult patient. Ceftriaxone was given in a single daily dose of 50 mg/kg to all children and 2.0 g to adult patients for 7-10 days. No adverse reactions were noted. Clinical improvement was achieved in all treated patients. Cultures became negative in 17 cases after the treatment. Significant bacteremia caused by P. aeruginosa persisted in 2 patients and by E. coli in 1 patient. No toxic effects on liver, renal, pancreatic and bone marrow functioning were seen. Ceftriaxone may be safely and efficiently used for the treatment of the urinary and respiratory infections. PMID- 2235714 TI - [The role of aromatic hydrocarbon hydroxylase in the pathogenesis of lung cancer]. AB - Aromatic hydrocarbons hydroxylase (AHH)--an enzyme of monooxydases group- catalyzes hydroxylation of polycyclic aromatic hydrocarbons yielding compounds of the direct cancerogenic properties. Inducibility determined genetically is a characteristic feature of AHH. Inducibility of AHH in patients with cancer of the lungs is higher than that in healthy population. According to some authors general population may be classified into three groups of : high, moderate, and low degree of AHH inducibility. A significant increase in the incidence of neoplasms related to an exposition to PAH was noted in patients with increased AHH inducibility. These neoplasms include: carcinoma of the lungs, mouth and larynx, cancer of the pharynx and leukoplakia. Moreover, the onset of these neoplasms is earlier than in subjects with moderate and low inducibility of AHH. PMID- 2235715 TI - [Health hazards of occupational exposure to asbestos dust]. PMID- 2235716 TI - [Whole body plethysmography]. PMID- 2235717 TI - [Primary biliary cirrhosis of the liver--current therapeutic possibilities]. PMID- 2235719 TI - [Chronic active hepatitis in alcoholics]. AB - In 42 chronic alcohol abusers liver biopsy was performed and chronic active hepatitis was diagnosed in 11 cases. In 4 cases etiology could be attributed to chronic HBV infection--they were positive for HBsAg in serum, three were positive for HBeAg and one case had anti-delta antibodies. In 7 cases etiology was obscure, at least in some of them alcohol could have been the underlying factor. Liver disease in these particular cases was clinically more severe than chronic active hepatitis due to infection with HBV and non-A, non-B viruses in non drinkers. Two cases progressed into liver decompensation despite 1 and 2 years of abstinence, respectively. Chronic active hepatitis in alcoholics constitutes a frequent pathology, its etiology is variable, in some cases obscure. PMID- 2235718 TI - [Procollagen Type III-N-terminal peptide as an indicator of hepatic fibrogenesis]. AB - An assay of procollagen peptide III in blood serum enables non-invasive assessment of fibrogenesis in the liver. An increased level of this peptide has been shown in the chronic aggressive hepatitis and liver cirrhosis. PMID- 2235720 TI - [Ultrasonographic images of liver neoplasms--comparison with histopathological findings]. AB - Ultrasound pictures taken in 100 patients with histologically confirmed primary of metastatic neoplasms of the liver were analysed retrospectively. The most frequent were hyperechogenic foci (43%). Hypoechogenic foci were found in 33% of the patients whereas mixed changes in the liver scans (hyper- and hypoechogenic) in 22%. Thirty seven per cent of the hyperechogenic foci were attributable to metastatic process. Hypoechogenic disorders were most frequently due to the primary cancer of the liver (20%). Mixed lesions were mainly produced by the cancer of large intestine and liver (41% and 27%, respectively). Metastases into the liver produced all three types of ultrasound pictures. The obtained results confirm the opinion that ultrasound picture of metastatic liver tumours is not suitable for the diagnosis of the type and origin of the neoplasm. PMID- 2235722 TI - [Evaluation of the capacity of the liver for phenazone biotransformation in patients with uremia on peritoneal dialysis]. AB - This work aimed at establishing whether liver ability to biotransformation of drugs expressed by antipyrine kinetics is disturbed in peritoneally dialysed patients with end-stage renal failure. The investigations were carried out in 10 uraemic patients using the antipyrine test and comparing antipyrine kinetics with those obtained in 13 healthy individuals. At the time of investigations, standard clinical tests of liver function were normal and HBs antigen was absent in all patients. It was shown that peritoneally dialysed patients with end-stage renal failure had not significantly changed antipyrine elimination as compared with the group of healthy controls: t0.5 = 13.2 +/- 6.8 v. 11.8 +/- 8.1 h, plasma clearance = 50 +/- 30 v. 34 +/- 21 ml/min (x +/- SD). The obtained results indicate that antipyrine kinetics is within normal range in uraemic patients regularly dialysed suggesting cytochrome P-450 in microsomes not being markedly reduced. PMID- 2235721 TI - [Plasma clearance of cholic acid in patients with chronic diseases of the liver]. AB - The diagnostic value of 14C-cholic acid plasma clearance following oral administration was evaluated. 14C-cholic acid clearance was 1223 +/- 267 mL/min. per 1 square meter in the control group without liver disease. Significantly lower values (p less than 0.001) were obtained in the patients with chronic hepatitis (694 +/- 137 mL/min. per 1 square meter) and liver cirrhosis (332 +/- 156 mL/min. per 1 square meter). Sensitivity of the 14C-cholic acid clearance test was 100% while specificity--80%. A 3-year follow-up has shown that this test is of high prognostic value in patients with liver cirrhosis. PMID- 2235724 TI - [Diagnostic difficulties in prajmaline-induced intrahepatic cholestasis]. AB - A case of prajmalium-induced intrahepatic cholestasis is presented. A proper diagnosis was delayed because differential diagnosis did not include toxic liver damage. Pathogenetic considerations included immunological background of the disease which improved completely within one year. No clinical and biochemical complications were seen. PMID- 2235723 TI - [Effect of pyrazinoic acid on the transport function of the peritoneum- experimental studies]. AB - Bidirectional transport of the urea, uric acid and albumin across parietal peritoneum was investigated in vitro under both normal conditions and following an administration of pyrazinoic acid. It was found that pyrazinoic acid decreased urea and uric acid transport from interstitial to mesothelial surface of the peritoneal membrane but did not affect the transport in reverse direction. Bidirectional transport of albumin remained unchanged. The obtained results are similar to those reported earlier and suggest that pyrazinamide actions are partially selective. PMID- 2235725 TI - [Development of autoimmune chronic active hepatitis after acute hepatitis B]. AB - A case of the autoimmunological chronic active hepatitis following the acute HBV infection is presented. A 24-year female patient underwent HBV infection and was hospitalized one year later due to persistent abnormalities in the activity of aminotransferases. Immunosuppressive therapy improved the results of the liver functioning tests and histological picture of the liver. An appropriate diagnosis is of importance as the chronic autoimmunological hepatitis respond to the treatment with corticosteroids. Such a treatment produced an improvement in the presented case. PMID- 2235726 TI - [A peculiar form of portal hypertension--the Budd-Chiari syndrome]. PMID- 2235727 TI - Role of calcium in the programmed death of rat prostatic glandular cells. AB - By using a newly developed and validated rat ventral prostatic organ culture system in which prostatic glandular cells can be induced to undergo programmed cell death, the role of an elevation in the intracellular free Ca2+ concentration in this death process was studied. By using this organ culture system, ventral prostatic glandular epithelial cells can be maintained in culture for a period of more than 14 days with a low daily rate of cell death (i.e., approximately 5% die per day) if androgen is included in the media. In contrast, if androgen is not included in the media, the daily rate of prostatic glandular cell death increases approximately 3-fold (i.e., approximately 15% die per day). With this organ culture system it has been demonstrated that the daily rate of programmed death of the glandular epithelial cells can be shifted from 5% to 15% of the cells dying per day when testosterone and 10 microM of the Ca2+ ionophore A23187 are both present in the media. Thus, when the intracellular free Ca2+ is elevated within prostatic cells by means of ionophore treatment, the daily rate of glandular cell death in the presence of testosterone is identical to that induced when testosterone is not present in the media. If the organ cultures are maintained in media lacking testosterone but containing 10 microM of the Ca2+ channel blocker nifedipine to inhibit elevations in the intracellular free Ca2+ derived from the extracellular pools, the rise in the daily rate of cell death from 5 to 15% of the cells dying per day induced by androgen ablation can be inhibited by approximately 70%. These results suggest that an increase within prostatic glandular cells in their intracellular free Ca2+ derived from extracellular Ca2+ pools is a critical early event involved in triggering the subsequent process of programmed cell death (i.e., specifically DNA fragmentation) in these cells following androgen ablation. PMID- 2235728 TI - Epidemiology of prostatic cancer: a case-control study. AB - A population-based case-control study of prostatic cancer in Alberta was undertaken to determine the risk factors associated with the disease. Cases were 382 newly diagnosed prostatic cancer patients and 625 controls, group-matched to the anticipated age distribution of the cases, chosen at random from the health insurance roster. Subjects were interviewed in their homes by using a pre-tested questionnaire including questions related to ethnic group, education, puberty, marital history, family history, residence, water supply, smoking, and diet. Factors significantly related to the risk of developing prostatic cancer included ethnic group (British high, Ukrainian low), education (elementary high, university low), age at first marriage (early high, late low), family history (high risk for those with relatives with prostatic cancer), and increased masculinity among the children of cases. The results with respect to smoking, occupation, medical history, birthplace, residence, water supply, and diet were generally negative. PMID- 2235729 TI - Differences in growth requirements between epithelial and stromal cells derived from rat ventral prostate in serum-free primary culture. AB - Different procedures of enzymatic digestion of rat prostatic tissue and unique sets of mitogenic factors made it possible to culture practically pure populations of epithelial and stromal cells without previous separation of the two types of cells. Keratin-positive epithelial cells dissociated by trypsin and collagenase from adult rat ventral prostate proliferated in medium WAJC 404 supplemented with epidermal growth factor, insulin, cholera toxin, and bovine pituitary extract. Proliferation of epithelial cells was completely inhibited by dexamethasone as low as 30 nM. On the other hand, fibroblast-like stromal cells released by trypsin digestion required a plastic substratum coated with calf serum or fibronectin, and proliferated in Eagle's minimum essential medium supplemented with cholera toxin, bovine pituitary extract, dexamethasone, and bovine serum albumin. Epidermal growth factor and insulin had negligible effect on proliferation of stromal cells. Physiological concentrations of dihydrotestosterone and estradiol showed no effect on proliferation of both types of cells. PMID- 2235730 TI - Experimental prostatitis in nonhuman primates: I. Bacterial adherence in the urethra. AB - Both man and monkey possess urothelial (transitional cell) receptors for P fimbriae of Escherichia coli; however, the male urethra has pseudostratified columnar cells. We studied adherence using scanning electron microscopy and found that P-fimbriae were the principal mediators of adherence to these cells as well. The monkey, therefore, should be a good model for the study of the ascending route of infection in prostatitis, the route thought to occur in man. PMID- 2235731 TI - Experimental prostatitis in nonhuman primates: II. Ascending acute prostatitis. AB - Bacterial prostatitis is a common cause of urinary tract infection in males, but little is known of its pathophysiology. To study this, we developed a nonhuman primate model using a wild-type clinical isolate of Escherichia coli. Primates have a prostatic anatomy that is similar to humans, which makes them ideal as an animal model of this disease. The monkeys had a urethral inoculation of this organism and were then followed with urine, blood, and semen cultures, white blood counts, and renal scans. They were sacrificed at from 10 days to 4 weeks, and their genitourinary tracts histologically examined. The prostatitis paralleled that reported in humans, and we conclude that the infection occurs by the ascending route. The organisms causing the infection in man do so in our primate model, and the histologic change is also the same. Thus, the primate model holds promise for studies to help us understand this disease. PMID- 2235732 TI - Effects of prolactin and androgens on the prostatic lipids of castrated mature bonnet monkeys. AB - The effects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihydrotestosterone (DHT), and the combinations of these androgens with PRL/Br on total lipid, total cholesterol, total glyceride glycerols, and total phospholipid and their fractions in cranial and caudal prostates of castrated mature monkeys were studied. Glyceride glycerols formed the major portion of total lipids (50%) in normal monkeys. Cholesterol and phospholipids were of equal share (25%). Esterified cholesterol formed the major share (75%) of total cholesterol. Diacyl glycerol was the major (60%) glyceride glycerol and phosphatidyl choline and ethanolamine were the major phospholipid classes. Except triacyl glycerol castration markedly decreased all the lipid classes in both the lobes. PRL restored normal free and esterified cholesterol and phosphatidyl inositol but Br invariably decreased all the lipid classes. TP/DHT treatment stimulated the free and esterified cholesterol more than the control; it restored the normal glyceride glycerols in both the lobes. Phosphatidyl inositol, choline, and ethanolamine were stimulated by androgens and other phospholipid classes were brought to normal in both the lobes. Addition of PRL + TP/DHT markedly increased esterified cholesterol, phosphatidyl inositol, choline, ethanolamine, and phosphatidic acid in both the lobes. Br counteracted the effects of androgens and prolactin. In general, the influence of prolactin was more in the caudal lobe than cranial. The results are discussed in detail with available literature. PMID- 2235733 TI - Mitchell's bunionectomy and Wu's bunionectomy: a comparison of 100 cases of each procedure. PMID- 2235734 TI - Distal soft tissue procedure and proximal metatarsal osteotomy for correction of hallux valgus deformity. PMID- 2235735 TI - Metatarsocuneiform arthrodesis for treatment of hallux valgus and metatarsus primus varus. PMID- 2235736 TI - Arthrodesis of the first metatarsophalangeal joint with mini-fragment plate fixation. PMID- 2235737 TI - Keller resection arthroplasty. PMID- 2235738 TI - Complications of hallux valgus surgery and salvage. PMID- 2235739 TI - Cemented bipolar arthroplasty. PMID- 2235740 TI - Ethics in orthopedic residency. PMID- 2235741 TI - Treating hallux valgus deformities: versatility is required. PMID- 2235742 TI - Pathophysiology, anatomy, and biomechanics of hallux valgus. PMID- 2235743 TI - Bunion surgery: decision making. PMID- 2235744 TI - Simple bunionectomy. PMID- 2235745 TI - The Chevron procedure. PMID- 2235746 TI - The modified McBride procedure. PMID- 2235747 TI - Results of Akin type proximal phalangeal osteotomy for correction of hallux valgus deformity. AB - The results of 26 Akin proximal phalangeal osteotomies in 22 patients for hallux valgus deformities are reported. The average follow up was 53 months (range, 12 to 97 months). Subjectively, 16 feet had a satisfactory result (61.5%). Objectively, 14 feet met the criteria for a satisfactory result (53.8%). The authors found that the Akin osteotomy was unpredictable as an isolated procedure, and not indicated in a hallux valgus deformity with an incongruent joint. PMID- 2235749 TI - [Sharpening technics for periodontal instruments]. AB - Different approaches to sharpening are described by the Authors with particular emphasis upon periodontal curettes. Recent findings are also reported and discussed. PMID- 2235748 TI - [Caries in 6 to 12-year old children in 6 towns of Usl n. 16 of Modena]. AB - A "screening" done by the "Servizio Materno Infantile" of Modena relative to children from 6 to 12 years old during 1988-89 is described. The research is referred to 1454 children 6 years old attending the second year of the secondary school. For the evaluation of the level of the dental health have been used the Oms Index. The results are very comforting: the 54% of the 6 years old children have sound teeth, but from the dmft Index with a value of 1.6 comes out the trend not to cure the caries of the deciduous teeth. Very few are the cases of 6 years old children with caries of the permanent teeth. At 12 years the percentage of children with sound teeth is lower (34%), however analyzing the DMFT Index (1.9) appears a very high degree of attention towards the dental care. PMID- 2235750 TI - [Prevention and school. Behavioral response of children and critical evaluation of teachers]. AB - The Authors have examined the spontaneous attitude of the children of the first elementary class during a day spent at the department of Odontostomatology in a course programme for education and prevention of caries. It was shown an extremely positive behaviour, with images principally centered on the trip between school and Hospital (the bus, the sight of the town). The teachers based on a day by day diary have demonstrated a positive impression on the various aspects of the initiative, stressing the importance of continuative relationship between doctors-teachers-parents. PMID- 2235751 TI - [Intervention for integrated dento-periodontal prevention]. AB - An epidemiological survey has been achieved on elementary and secondary schoolchildren of five different areas in the territory of Ussl no 16 in Lecco. The study, performed on a randomly sample of 458 children aged 6, 10, 12 years, used the epidemiological indexes DMFT/dmft and CPITN to monitor dental and periodontal status. The treatment needs of the subjects was monitored too and the amount of Streptococco mutans in 6 years old schoolchildren, using spittle drawning, was investigated. The results seem to show that the DMFT/dmft values are on a moderate level as regards the European goals, while the amount of dental and periodontal treatment performed is very low. The gingivitis prevalence is high, as well as scaling is required in many children. The analysis of the spittle samples drawned in 6 years old schoolchildren points out high levels of Streptococcus mutans as regard those collected in other similar studies achieved by our Department. According to the results analysis, two sorts of preventive intervention were planned to have the maximum preventive efficacy according to the disease level located in the different areas. PMID- 2235752 TI - [Assisting in endodontics]. PMID- 2235753 TI - [Home oral hygiene instructions]. PMID- 2235754 TI - [Epidemiological study of the incidence of dental caries]. AB - The aim of this work is the evaluation of the results of an epidemiological survey on dental caries in schoolchildren in Arezzo and the province of Arezzo. The examined patients were 492, between the ages of 8 and 12, all of whom were at Primary School, in their third, fourth or fifth year. The evaluation of the data, which has been collected in other statistics in recent years, focussed on the measurement of caries in primary molars and upper incisors. The total occurrence of cases in which either the caries were present, or had already been cured, amounted to 62.4% of the total sample. It also seems as if there is a progressive increase in the instance of caries between the third year (45%) and the fifth year (68%) of Primary School. In addition it is worth noting that there is a higher incidence of caries among subjects in urban areas. PMID- 2235755 TI - [Sealants: indications, contraindications, technique]. PMID- 2235756 TI - [Space analysis and treatment planning in the mixed dentition]. AB - The maintaining of the space during mixed dentition, allows the patient to obtain a good occlusion, the right growth and facial development. The orthodontist can preserve the space, using simple appliances like the lip bumper and the lingual arch. PMID- 2235757 TI - Pulmonary elastic fibers in normal human development and in pathological conditions. AB - Normal human pulmonary elastic fiber development and development in some pathological conditions were examined using elastic stains by light microscopy, electron microscopy, and immunohistochemistry. In normal development elastic fibers, composed mainly of microfibrils, first appeared around primitive bronchioles at 10 weeks of gestation. As they matured, their appearance became more amorphous, and they extended into the peripheral alveolar walls. Development of elastic fibers was retarded in the hypoplastic lungs of the oligohydramnios syndrome, diaphragmatic hernia, and hydrops fetalis. Elastic development was also retarded in congenital pulmonary lymphangiectasia and in focal areas of lungs with pulmonary dysplasia. Distribution of well-developed elastic fibers was found around the dilated bronchioles and alveoli in cases of congenital cystic adenomatoid malformation and extralobar pulmonary sequestration. Elastic fibers were distributed irregularly and unevenly in the lungs of bronchopulmonary dysplasia and ventilated cases of Wilson Mikity syndrome. In addition, four very immature infants who had progressively deteriorating respiratory function showed an almost total lack of elastic fibers in their alveolar walls. PMID- 2235758 TI - Simple autopsy method for analysis of complex fetal cranial malformations. AB - A new radiography technique for examining second trimester abortions permits an accurate analysis of growth and maturation of the fetal skull. Reference material for normal development has been previously published. The potential of the method is demonstrated with three examples: thanatophoric dysplasia, Arnold-Chiari malformation, and anencephaly. PMID- 2235759 TI - Fatal malformations in Jamaica. AB - Babies with major malformations were identified during the Jamaica Perinatal Morbidity and Mortality Survey. They were found in 96 (8.6%) of 1112 perinatal and neonatal deaths coming to necropsy and in 28 (2.6%) of 1085 no so examined. The central nervous system was most commonly affected, followed by the renal, gastrointestinal, and cardiovascular systems in decreasing order of frequency. Many infants had abnormalities in more than one system and 10 malformation syndromes/sequences were identified. Although at the present time, major malformations make only a small contribution to perinatal and neonatal mortality in Jamaica, their importance will increase when deaths from other causes, such as birth asphyxia, decline. The type of malformation currently fatal in a particular population is relevant when planning diagnostic and surgical services for neonates and infants. It is also important to any discussions about provision of prenatal diagnostic services. PMID- 2235760 TI - Correlation between pathologic and ultrasound findings in first trimester spontaneous abortions. AB - We compared the pathologic and ultrasonographic findings of 31 first trimester spontaneous abortions to determine the benefits of such studies. The ultrasound diagnoses included empty gestational sac (n = 11), intrauterine fetal death (n = 11), abortion in progress or incomplete abortion (n = 8), and live embryo (n = 1). Two subgroups of empty sacs were identified by pathologic examination. Embryonic development appeared to be more advanced in one group as indicated by the presence of embryonic red blood cells (RBC's) in the placental vessels. Although an embryo or fetus was identified more frequently by sonar than by pathologic examination, we were able to diagnose developmental anomalies in small embryos that current ultrasound equipment cannot resolve. Such anomalies were identified even in the presence of fetal heart activity. Pathologic examination was also informative when heavy bleeding obscured the contents of the uterine cavity to sonar and was thus supplementary of a suboptimal ultrasound examination. Placental examination proved to be reliable in assessing gestational age at the time of embryonic/fetal death. There was a good correlation between RBC morphology and sonographic measurement of crown-rump length. First trimester ultrasound and pathologic examination of the embryo and placenta are informative and complement each other. PMID- 2235761 TI - Clinicopathological differences between early-onset and late-onset sepsis and pneumonia in very low birth weight infants. AB - We performed clinicopathological studies on early-onset sepsis (5 infants, less than 72 hours of life, EOS) and late-onset sepsis (15 infants, greater than 72 hours, LOS) of very low birth weight, less than 1500 g (VLBW). In EOS, the clinical features mimic the respiratory distress syndrome and hematological changes were not observed. The lungs showed slight interstitial pneumonia with structural immaturity, hyaline membranes, hemorrhage, and minimal infiltration by polymorphonuclear neutrophils (PMNs). The pathogen was group B streptococcus or weakly gram-negative bacilli. In LOS, pneumonia proceeded to sepsis and neutropenia with elevated numbers of circulating immature neutrophils, and increased levels of C-reactive protein were observed at the onset of sepsis. Severe pneumonia with infiltration of numerous PMNs and bacterial colonies and polymicrobial infection by nosocomial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa were common. The thymus and spleen weights varied but retained normal structure in EOS. The thymus was depleted of lymphocytes, and the spleen was hypertrophic but poorly reactive against infection in LOS. The pathogenesis of EOS is regarded as being more closely correlated with lung immaturity and circulatory disorder in early life, whereas that of LOS is associated with immunological defenses of the host, potency of the pathogens, and terminal multiple organ failure. PMID- 2235762 TI - Sudden, unexpected, natural death in childhood. AB - One thousand nine hundred and fifty four autopsies performed at British Columbia's Children's Hospital during a 7-year period were reviewed to determine the causes of sudden unexpected natural death in the age group from birth to 17 years. Of the 126 cases found, the largest group, 86 cases, was sudden infant death syndrome (SIDS). Nine deaths were the result of infection: 4 cases of H. influenza meningitis, 2 cases of meningococcemia, 2 cases of acute epiglottitis, and 1 case of necrotizing tracheobronchitis. Epilepsy, ruptured AV malformations, and brain tumors combined to make up an equally large group of 9 cases. Cardiac lesions were the third largest group, 6 cases. The three groups that posed the most difficulty in assigning a cause of death were (a) the group that were like SIDS yet had other confounding features, (b) the group in which metabolic death was suspected but not proven, and (c) death in epilepsy. PMID- 2235763 TI - Malignant mesenchymoma associated with a congenital lung cyst in a child: case report and review of the literature. AB - Primary lung tumors are uncommon in children, and malignant mesenchymal tumors form only a small proportion of these. Leiomyosarcomas occur more commonly than rhabdomyosarcomas, whereas malignant mesenchymomas are exceedingly rare. Of the total number of primary pulmonary rhabdomyosarcomas and malignant mesenchymomas of lung reported in children, 50% have occurred in association with congenital lung cysts. The relationship between abnormal morphogenesis and neoplasia is well documented in the kidney. A similar relationship may exist in the lung between cystic parenchymal maldevelopment and embryonal mesenchymal tumors. We report a 4 year-old boy with a malignant mesenchymoma of lung arising within a congenital lung cyst; one similar case has previously been reported to our knowledge. PMID- 2235764 TI - Foregut choristoma of the ileum, (adenomyoma)--a case report. AB - An ileal adenomyoma in a 7-year-old boy who presented with jejunoileal intussusception is described and the term "foregut choristoma" is proposed for this and related conditions, such as ectopic pancreas or heterotopic Brunner's glands in the gastrointestinal tract. The polypoid mass in the ileum of this patient was composed of cystically dilated glandular structures lined by a tall columnar epithelium resembling hepatobiliary or pancreatic ductal epithelium, hypertrophic and irregular smooth muscle bundles surrounding the glandular elements, and small amount of fibrous stroma. Reported cases of this disorder in the gastrointestinal tract are generally confined to the antrum of the stomach. PMID- 2235765 TI - "Marden-Walker syndrome": neuropathologic findings in two siblings. AB - Neuropathologic examination of two siblings with phenotypic features consistent with Marden-Walker syndrome revealed central nervous system abnormalities which include reduction in the number of spinal anterior horn cells. The occurrence of these changes in a sibling pair provides strong evidence for a genetic etiology. The relationship between the neuropathologic changes and other phenotypic manifestations in this syndrome and in the closely related syndrome of Pena Shokeir are discussed. PMID- 2235766 TI - Pneumomyocardium: an unusual complication of barotrauma. AB - We report a 22-day-old infant who developed Staphylococcus aureus pneumonia with abscesses, pneumatoceles, and sepsis at 10 days of life. Mechanical ventilation was complicated by pneumothorax. At autopsy, a collection of air was found in the interventricular septum of the heart, a lesion we have termed pneumomyocardium. No hemorrhage, inflammatory infiltrate, organisms, or necrotic debris was found on the edge of the area of interstitial emphysema in the heart. We believe that the pneumomyocardium arose as a consequence of barotrauma. PMID- 2235767 TI - Combined true thymic hyperplasia and lymphoid hyperplasia in Graves' disease. AB - True thymic hyperplasia (enlarged gland composed of histologically unremarkable cortical and medullary parenchyma) and lymphoid hyperplasia (medullary lymphoid follicles in the clinical setting of autoimmunity) usually develop as independent pathologic processes. We reviewed the clinical features and gross and microscopic pathology of 2 hyperthyroid patients with features of both thymic hyperplasia and lymphoid hyperplasia. The diagnosis of thymic hyperplasia was supported by thymic weights greater than two standard deviations above the mean weight for age and histologic evidence of expanded cortical and medullary parenchyma. The diagnosis of lymphoid hyperplasia was supported by the increased number and size of medullary lymphoid follicles and the association with Graves' disease. This unusual combination results from two separate pathogenic mechanisms operating simultaneously in hyperthyroid patients. Elevated thyroid hormones directly stimulate the proliferation of thymic epithelium, producing thymic hyperplasia. The immune abnormalities underlying Graves' disease can also result in lymphoid hyperplasia of the thymus. PMID- 2235769 TI - The role of the pediatrician in school health. PMID- 2235768 TI - Sudden and unexpected death--a late effect of occult intraesophageal foreign body. AB - Acute upper airway obstruction in a 4-month-old male infant who presented as sudden infant death syndrome is described. At autopsy external tracheal compression and tracheobronchitis with plugging of the trachea and bronchi by an abundant mucopurulent exudate were found. The source of the inflammation was the adjacent esophagus where previous impaction of a coin had caused pressure necrosis with mucosal erosion and transmural granulation tissue formation. This case is reported to demonstrate that foreign bodies that remain in the esophagus, having by-passed the larynx, may still result in upper airway obstruction and death in early infancy by this unusual mechanism. PMID- 2235770 TI - Muscle disease in children: a practical approach. AB - This paper has given an overview of the complexity of childhood muscle disease. Fortunately, astute history-taking and physical examination, combined with readily available tests, will usually enable the clinician to formulate a diagnosis and plan of management. PMID- 2235771 TI - Lower gastrointestinal bleeding. AB - The differential diagnosis of lower gastrointestinal bleeding in children can be reduced markedly simply by taking into account the age of the child. The clinical condition of the patient can further help narrow the diagnostic possibilities. Newborns and infants who are clinically unstable are more likely to have diseases such as necrotizing enterocolitis, volvulus, Hirschprung disease, intussusception, or Meckel diverticulum. A baby who appears healthy should be examined for swallowed blood, allergic colitis, anal fissures, or lymphonodular hyperplasia. An older child of healthy appearance with bleeding is likely to have a juvenile polyp or infectious colitis, but a child who appears sick may have hemolytic uremic syndrome, Henoch-Schoenlein purpura, or inflammatory bowel disease. This information, along with that gleaned from the physical examination, can lead the pediatrician to determine the need for specific tests, such as abdominal radiographs, stool cultures, and an endoscopic evaluation. We have come a long way in our ability to diagnose the causes of lower gastrointestinal bleeding. With the availability of newer radiographic and nuclear medicine modalities and the ability to visualize the colon endoscopically, the need for exploratory laparotomy for diagnosis is rarer. While surgery may still be the therapy of choice, new diagnostic modalities give the surgeon much more preoperative information. PMID- 2235772 TI - Steroids: breakfast of champions. PMID- 2235773 TI - Diagnosis and management of upper gastrointestinal tract bleeding in the pediatric patient. PMID- 2235774 TI - Juvenile dermatomyositis: a clinical overview. AB - The child who develops the symptoms of the specific rash, proximal muscle weakness, and fatigue should seek medical care promptly. With the advances in physical and medical therapy, many of the consequences of the disease can now be ameliorated. There are suggestive data that JDMS and PM may each have a different pathophysiology, but more evidence is needed. The next few years should be exciting as there is increased effort to determine if there is, in fact, a causal relationship between Coxsackievirus B or other enterovirus and genetic factors that alter the susceptibility to or severity of the course of the disease. PMID- 2235775 TI - The satisfactions of pediatric practice. PMID- 2235776 TI - Let's stop the comeback of tuberculosis. Best drug regimens for prevention and treatment. AB - Tuberculosis has been on the increase in recent years, so physicians need to be aware of it once again. Very effective drugs are available to treat the disease. Pharmacokinetics, dosing schedule, and adverse reactions of each anti-tuberculous agent need to be considered. A short (6-month) course of therapy is now recommended: Isoniazid, rifampin (Rifadin, Rimactane), and pyrazinamide are given for the initial 2 months, followed by isoniazid and rifampin for 4 months. If drug resistance is a factor, a fourth drug is added to the initial regimen, and therapy may have to be extended. Chemoprophylaxis with isoniazid is very important to reduce the incidence of tuberculosis. It should be given to all high risk persons. PMID- 2235777 TI - Get Congress to kill the malpractice dragon. PMID- 2235778 TI - Why Nathan? PMID- 2235779 TI - Colonoscopy in critically ill patients. What conditions call for it? AB - Indications for colonoscopy in the intensive care unit include acute lower intestinal bleeding, sigmoid volvulus, pseudo-obstruction of the colon, and suspicion of pseudomembranous colitis. Although the incidence of cardiorespiratory complications may be higher in these critically ill patients, the procedure can be done safely with proper attention to detail. Because of colonic dilatation, endoscopy can often be done without bowel preparation. PMID- 2235780 TI - When epilepsy masquerades as heart disease. Awareness is key to avoiding misdiagnosis. AB - Autonomic neural impulses that accompany discharges during a seizure can cause a variety of cardiac manifestations, including cardiac arrhythmias, sudden death, anginal chest pain, neurogenic pulmonary edema, and symptoms of pheochromocytoma. Either generalized or focal seizures may generate such signs and symptoms. A better appreciation of cardiac problems caused by epilepsy is helpful in preventing misdiagnosis, because the clinical picture in such a patient may be confusing. PMID- 2235781 TI - When a patient with a bleeding disorder needs dental work. How you can work with the dentist to prevent a crisis. AB - Patients with bleeding disorders need close cooperation between their physician and their dental practitioner to receive safe, comprehensive dental care. When indicated, physicians must advise a compromised treatment plan to avoid deep injections or surgical procedures that may initiate a bleeding crisis in patients at risk. The conditions most commonly seen that require special consideration are long-term use of antithrombotic agents, platelet dysfunction caused by chronic renal failure, and congenital clotting factor deficiencies. Even these patients may undergo a high-risk procedure, such as periodontal surgery, with adequate precautions and preparation. PMID- 2235782 TI - Treating diabetes in the elderly. What are the special considerations? AB - Management of diabetes in elderly patients generally follows the same lines as in younger patients; that is, improvement of blood glucose status with diet, oral hypoglycemic, and insulin therapy as required. Older patients are more fragile, however, and more caution must be used with therapeutic interventions. PMID- 2235783 TI - Eosinophilia-myalgia syndrome linked to tryptophan. AB - Eosinophilia-myalgia syndrome has been linked to ingestion of tryptophan, but the exact cause of this recently recognized syndrome is unclear. As in other reported cases, the disease in the patient described here developed while she was taking tryptophan. Although eosinophilia resolved following glucocorticoid therapy, the disease in this patient continues to progress. PMID- 2235784 TI - Ketoconazole for prostate cancer. PMID- 2235785 TI - Toscanini's fumble. PMID- 2235786 TI - Tutorial approach to medical education. PMID- 2235788 TI - Potentially lethal ventricular arrhythmias. Minimizing the danger. AB - Patients with potentially lethal ventricular arrhythmias are at an increased risk of sudden death. Antiarrhythmic drugs, with the exception of beta blockers and possibly amiodarone, have not been particularly effective in reducing mortality. Beta blockers have been used successfully to treat survivors of myocardial infarction, including patients with significant impairment of ventricular function. Evidence to date suggests that use of low-dose amiodarone may be appropriate for selected patients with chronic heart failure and potentially lethal ventricular arrhythmias. PMID- 2235787 TI - Arrhythmias in patients with CHF. Should they be treated? AB - Ventricular arrhythmias are a major cause of death in patients with congestive heart failure. Dr Ellenbogen and his associates discuss the current thinking, based on recent studies, concerning use of antiarrhythmic agents to prevent sudden cardiac death in these patients. As they point out, the proper antiarrhythmic therapy may be crucial to long-term survival. PMID- 2235789 TI - Abdominal trauma in pregnancy. When is fetal monitoring necessary? AB - The type and duration of observation and monitoring of mother and fetus after abdominal trauma are dependent on gestational age and severity of trauma. Fetal monitoring is usually not required when the fetus is not viable; the primary consideration is the safety of the mother. When the fetus is viable, 24-hour inpatient fetal monitoring is indicated in cases of major trauma, even when no symptoms of injury are obvious. PMID- 2235790 TI - What to do about pruritus scroti. AB - Pruritus scroti is a common clinical disorder that is caused by various inflammatory disorders, infections, infestations, and neoplasms. Laboratory evaluation, including bacterial and fungal cultures, microscopic examination, skin biopsies, and measurement of blood glucose levels, is useful in establishing the diagnosis. Management of pruritus scroti includes avoidance of irritants, allergens, and restrictive clothing and use of topical and systemic agents that provide both symptomatic relief and specific treatment of the underlying cause. PMID- 2235791 TI - Summer heat illnesses. PMID- 2235793 TI - Viral pneumonias. A diagnostic and therapeutic challenge. AB - Viral pneumonias are both a diagnostic and a therapeutic challenge for primary care physicians. The illness should be suspected when an upper respiratory tract infection progresses to include dyspnea and cyanosis. Rapid diagnostic tests are now available to detect most of the viruses that cause pneumonias. Fortunately, viral pneumonias usually resolve without specific antiviral therapy; however, ribavirin is indicated for respiratory syncytial virus pneumonia in children and ganciclovir sodium (Cytovene) for cytomegalovirus pneumonia in immunocompromised patients. Acyclovir (Zovirax) is indicated for pneumonias due to herpes simplex virus and varicella-zoster virus infections. A high index of suspicion for bacterial superinfections is essential to reduce the risk of death from this complication. PMID- 2235792 TI - Pneumococcal pneumonia. Recognizing and treating this persistent disease. AB - Pneumococcal pneumonia remains a life-threatening disease despite the availability of many active antimicrobial agents and an effective vaccine. Dr Markowitz discusses why the disease persists, how it is diagnosed and treated, and what can be done to reduce its incidence. PMID- 2235794 TI - Mycoplasmal pneumonia. Are you thinking of atypical presentations? AB - The presentations of mycoplasmal pneumonia can be varied and sometimes complicated. The atypical nature of this illness, as opposed to the clear pattern of findings in classic bacterial pneumonias, leads the physician to the diagnosis. Appropriate therapy then allows quick improvement as a rule, with few sequelae. PMID- 2235796 TI - Why was this patient still in the hospital? PMID- 2235795 TI - What to do in case of an unthinkable chemical warfare attack or accident. AB - Successful management of casualties in a toxic chemical attack or accident depends on planning, preparation, and training. In many communities, physicians join other emergency rescue personnel to take part in periodic exercises and drills. In case of a large-scale attack or accident, all medical care providers will be needed to care for casualties. Chemical warfare agents are generally considered to be highly toxic, exotic materials, but most are not. Nerve agents are similar to, although more potent than, commonly used insecticides; cyanide and phosgene are widely available; the incapacitating agent BZ has effects identical to those of scopolamine; and most physicians with knowledge of chemotherapy are familiar with the effects of mustard. Although a chemical attack might be perceived as an uncontrollable disaster, the guidelines for successful management are the same as for any toxic chemical accident. Medical care of casualties depends on knowledge of the agent and timely intervention, and those responsible for such care must be ready. PMID- 2235797 TI - Mitral valve prolapse. When is it serious? AB - Mitral valve prolapse can best be diagnosed with careful clinical evaluation, including dynamic auscultation. Treatment consists of reassurance, pharmacotherapy for troublesome symptoms, and careful monitoring for signs of complications. Most complications can be either prevented or treated. PMID- 2235798 TI - The persistent vegetative state: time for caution? PMID- 2235799 TI - Psychiatry. PMID- 2235800 TI - Failure of thiazide diuretics to increase plasma calcium in mild primary hyperparathyroidism. AB - Thirteen patients with mild primary hyperparathyroidism who were taking thiazide diuretics intermittently for periods of up to 18 months were followed up for a mean of 5.3 years. No significant difference was found in either plasma total calcium corrected for albumin or whole blood ionized calcium in these patients between the periods on or off thiazides. We conclude that thiazide diuretics are not contraindicated in such patients. PMID- 2235801 TI - Do non-steroidal anti-inflammatory drugs or smoking predispose to Helicobacter pylori infection? AB - Susceptibility to Helicobacter pylori infection is a poorly understood phenomenon. This study was undertaken to establish whether either smoking or chronic non-steroidal anti-inflammatory drug (NSAID) consumption might in some way predispose to H. pylori infection and hence lead to peptic ulceration. Serological evidence of H. pylori infection was assessed in 100 consecutive subjects receiving NSAIDs without any evidence of gastrointestinal upset and 100 matched controls. All subjects had a full assessment of their smoking habits. Sixty-three per cent of patients taking NSAIDs compared to 51% of controls had evidence of H. pylori infection (NS). Smoking habit also had no effect on H. pylori colonization. The ulcerogenic potential of NSAIDs and smoking does not appear to be mediated via a prediposition to H. pylori infection. PMID- 2235802 TI - Gastric antral vascular ectasia (watermelon stomach)--therapeutic options. AB - We have encountered five cases of chronic iron deficiency anaemia due to bleeding from gastric antral vascular ectasia (watermelon stomach). Two cases were associated with a lymphoma and in three cases there was evidence of portal hypertension. Two patients were treated conservatively by blood transfusions. The other patients required either surgery or tranexamic acid or endoscopic laser therapy to control the chronic haemorrhage. PMID- 2235803 TI - Relationship of urinary pH to symptoms of 'cystitis'. AB - The pH of urine samples from patients suffering symptoms suggesting urinary infection (e.g. dysuria, frequency, urgency) was measured while the patients were symptomatic and again when they had become asymptomatic. There was no correlation between the urine pH and the incidence or number of symptoms. No differences were observed between either the distribution or means of urine pH values in symptomatic and asymptomatic patients. There were also no significant differences in either symptomatology or urine pH between patients with significant bacteriuria and those without significant bacteriuria. These results cast doubt upon the traditional (but unproved) belief that alkalinizing the urine helps to reduce symptoms of dysuria and/or frequency, whether or not associated with urinary infection. PMID- 2235804 TI - Anicteric hepatitis and uveitis in a worker exposed to trichloroethylene. AB - A previously healthy woman developed acute anicteric hepatitis which slowly resolved, though bilateral anterior uveitis then appeared. No other cause than an occupational exposure to trichloroethylene was found, and rechallenge by resuming work has led to a transient increase in serum alkaline phosphatase. Both manifestations may constitute a rare systemic reaction to trichloroethylene. PMID- 2235805 TI - Reactivation of latent melioidosis. AB - Reports of melioidosis in residents of European countries are rare. We describe a case of reactivation of latent melioidosis in a United Kingdom resident. The case demonstrates the lack of clinical response to chemotherapy despite proven in vitro sensitivity of the organism to the drugs used. It is important to consider melioidosis as a cause of septicaemic illness in patients who have travelled to, or been resident in South-East Asia. PMID- 2235806 TI - Spreading sepsis by cystoscopy. AB - A healthy 54 year old man was investigated for haematuria. In spite of a proven urinary tract infection a cystoscopy was carried out with no antibiotic therapy. As a result he developed systemic infection leading to two independent, and potentially fatal, complications: vertebral osteomyelitis and a mycotic false aneurysm. PMID- 2235807 TI - Abdominal mass. PMID- 2235808 TI - Stress and stress counselling. AB - This is a report by the 1989 National Association of Clinical Tutors Wyeth Travelling Fellow to the United States of America. The stresses of postgraduate training and attempts to modify these are described, including stress counselling. The significance of stress and the relevance of the findings for postgraduate training in the United Kingdom are considered. PMID- 2235809 TI - Clinical hyperthyroidism due to non-neoplastic inappropriate thyrotrophin secretion. AB - We report a case of hyperthyroidism due to inappropriate thyrotrophin (TSH) secretion in a patient with selective pituitary resistance to thyroid hormone action. Symptoms of hyperthyroidism in patients with this disorder are usually mild, implying some peripheral tissue resistance to the metabolic effects of thyroid hormone. Our patient had unusually severe symptoms, including marked weight loss and cardiac arrythmias which required carbimazole and beta-blocker therapy for control. Somatostatin was ineffective in suppressing TSH secretion. The introduction of sensitive thyrotrophin assays should facilitate the accurate diagnosis of TSH-induced hyperthyroidism and avoid inappropriate treatment. PMID- 2235810 TI - Carotid artery stenoses and thrombosis secondary to cavernous sinus thromboses in Fusobacterium necrophorum meningitis. AB - We report the case of a young man with Fusobacterium necrophorum meningitis who developed bilateral carotid artery stenosis associated with thrombosis of the cavernous sinuses. Intraluminal clot was present in the region of the stenoses for which he was anticoagulated. The clinical presentation, problems with diagnosis, the use of anticoagulation and the need for prolonged treatment with metronidazole are discussed. PMID- 2235811 TI - Intermittent hypercalcaemia and vitamin D sensitivity in Hodgkin's disease. AB - A patient with Hodgkin's disease spontaneously developed steroid-responsive hypercalcaemia during two consecutive summers. Administration of 3000 U/day of vitamin D, while he was normocalcaemic, caused a sharp increase in serum 1,25(OH)2D3 (from 59 pg/ml to 142 pg/ml) and subsequently hypercalcaemia while serum 25(OH)D3 rose moderately within the normal range (from 2.8 ng/ml to 10 ng/ml). During a spontaneous episode of hypercalcaemia which was accompanied by increased circulating 1,25(OH)2D3 concentrations, administration of hydrocortisone decreased serum 1,25(OH)2D3 rapidly (from 115 pg/ml to 62 pg/ml) and eventually led to normocalcaemia while serum 25(OH)D3 remained unchanged. Thus the disturbances of mineral metabolism found in this patient with Hodgkin's disease are very similar to those previously described in sarcoidosis. PMID- 2235812 TI - A case of POEMS syndrome associated with essential thrombocythaemia and dermal mastocytosis. AB - We describe a case of POEMS syndrome presenting with the recognized features of polyneuropathy, organomegaly, endocrine abnormalities, monoclonal protein, skin changes and anasarca. The patient was found to have both a solitary sclerotic plasmacytoma of the pelvis and evidence of Castleman's disease of lymph nodes. A number of unusual and unique features are also documented. Histological examination of affected skin demonstrated changes similar to urticaria pigmentosa including local oedema and mast cell infiltration. There was marked thrombocythaemia which has been seen in only one previous case and in addition the patient developed diffuse vascular calcification in the absence of recognized aetiological factors. Radiotherapy of the pelvic lesion and chemotherapy to control the myeloproliferative disorder gave rise to significant improvement in neuropathy. Control of anasarca required steroid therapy in addition to diuretics. The significance of these observations is discussed in relation to previous reports. PMID- 2235813 TI - Erosive arthritis in relapsing polychondritis. AB - We report the case history of a 57 year old man who has suffered from typical deforming, relapsing polychondritis for 13 years. He has also developed erosive destructive seronegative polyarthritis involving some of his distal interphalangeal, proximal interphalangeal, metacarpophalangeal, intercarpal, wrist, intertarsal and metatarsophalangeal joints. The distribution of joint involvement in the small joints of the hands and feet is asymmetrical. Both hips and knee joints have also been involved necessitating bilateral total hip and right total knee replacement. The articular associations with relapsing polychondritis are discussed. PMID- 2235814 TI - Psoas abscess as a complication of subclavian venous catheterization. AB - A 76 year old woman developed a psoas abscess from vascular seeding of an infected subclavian venous catheter. The presentation was insidious and diagnosis delayed. Despite adequate surgical drainage, the case proved to be fatal. Venous catheters should be regarded as a potential source of septicaemia and occult abscess formation. PMID- 2235815 TI - Immunotactoid glomerulopathy associated with mycosis fungoides. AB - A patient with mycosis fungoides developed a nephrotic syndrome. Renal biopsy revealed deposits of a highly organized fibrillar material which did not stain with the typical amyloid stains; this picture was consistent with the diagnosis of non-amyloidotic fibrillary glomerulopathy or immunotactoid glomerulopathy. We believe this is the first case reported of immunotactoid glomerulopathy associated with mycosis fungoides. Possible pathogenetic implications are discussed with reference to previous publications. PMID- 2235816 TI - Cutaneous myiasis in an elderly debilitated patient. AB - A 77 year old woman, with chronic immobility, developed bed sores which became infested with maggots. This progressed to cutaneous myiasis which is an uncommon complication of this particular phenomenon. PMID- 2235817 TI - Synchronous adenocarcinoma and primary malignant lymphoma of the stomach. AB - A synchronous presentation of an adenocarcinoma and a primary low grade B cell lymphoma of the stomach is reported in a 79 year old man. Both diagnoses were made on endoscopic biopsies and immunocytochemistry was essential in confirming the lymphoma. The true incidence, aetiology and spatial relations of these tumours are unknown since only few cases of such synchronous gastric tumours have been reported in the literature. PMID- 2235819 TI - Conversation piece--the Medical Defence organisation doctor. Interview by P.D. Welsby. PMID- 2235818 TI - Ursodeoxycholic acid therapy in chronic active hepatitis. AB - A 41 year old woman developed chronic active hepatitis with prominent cholestasis. She was treated with prednisolone over 3 years with symptomatic benefit and improvement in serum biochemistry. However, various steroid-related side effects were encountered and steatorrhoea eventually occurred with very troublesome nocturnal diarrhoea. Therapy with ursodeoxycholic acid 750 mg daily was started. Serum alanine aminotransferase and gamma-glutamyl transferase normalized for the first time since her illness began. Steatorrhoea was abolished. There was good control of symptoms as prednisolone therapy was gradually reduced. However, when prednisolone was completely withdrawn there was a prompt biochemical deterioration. Addition of low-dose azathioprine has maintained normal blood tests over 24 months without return of the original symptoms. There are no side effects of ursodeoxycholic acid in subjects without gallstones and this agent may be effective treatment for cholestatic liver disease. PMID- 2235820 TI - Duodenal tuberculosis--a continuing diagnostic challenge. PMID- 2235822 TI - Snoring as the presenting feature of hypothyroidism. PMID- 2235821 TI - Brachial diplegia as a sequel to cardio-respiratory arrest: 'man-in-the-barrel syndrome'. PMID- 2235823 TI - Pneumococcal bacteraemia: a late complication following endoscopic variceal sclerotherapy. PMID- 2235824 TI - Borate G-banding technique applicable to in situ deoxyribonucleic acid/deoxyribonucleic acid hybridized chicken chromosomes. AB - The borate G-banding technique produced excellent longitudinal bands similar to trypsin G-bands on chicken chromosomes prepared from embryo material. Aged chromosome preparations on slides were pretreated in borate buffer (pH 9.2) for 10 to 30 s at 37 C, then stained in Giemsa solution. This simple G-banding procedure gave high-resolution chromosome banding and permitted the visualization of silver grains that localized cloned gene sequences or cloned DNA fragments to specific regions by in situ hybridization. PMID- 2235825 TI - Divergent selection for body weight and yolk precursor in Coturnix coturnix japonica. 8. A summary of correlated responses. AB - Correlated response data accompanying 19 generations of selection for increased (HW) or decreased (LW) 4-wk BW and increased (HP) or decreased (LP) total plasma P were summarized. Similarly, 11 generations of selection of sublines derived from the original Lines HW and LP were also analyzed. Sublines were maintained through selection of males for increased 4-wk BW and females for the respective high or low plasma P. The randombred control (RBC1) was stable for BW early in egg production, BW change from early to late in production, wet and dry liver weights, 120-day egg production, and ova weight. A linear decrease in BW was found for the RBC1 line late in egg production, egg and respective component weights, and ova number. Body weight early and late in the production period for original Lines HW and LW was different from the RBC1 line. Wet liver weight increased for the HW line while dry liver weights declined in the original Lines LW, HP, and LP. Egg weights were greater in Line HW and lower in Lines LW, HP, and LP than in the RBC1 line. Yolk weight increased in Line HW and decreased in Lines LW and LP. Albumen weight was reduced in Line LP while shell weight was increased in Line HW and decreased in Line HP. Egg production, from onset to 120 days, decreased in Lines HW and LW when compared to the RBC1 line. Line LP had more follicles in rapid development than Line RBC1. The sublines responded similarly to their line of origin differing only in the magnitude of response. This was a reflection of the mating scheme, which placed selection pressure on BW of males and plasma P in females. PMID- 2235826 TI - A comparison of flow cytometry and other techniques used for diagnosing Mycoplasma infections. AB - Mycoplasma isolates from chickens are usually identified by a fluorescent antibody (FA) technique that requires 7 to 10 days from sampling to the completion of identification. The FA procedure uses Mycoplasma-positive antibodies conjugated with fluoroisothiocyanate (FITC) to identify the colonies of the organism on agar. This paper describes a flow cytometric procedure that uses the same antibody-FITC conjugate and can be completed in 3 or 4 days. Broilers and egg-type hens inoculated with Mycoplasma gallisepticum and M. synoviae were swabbed from the choanal cleft and cultures were grown in broth. Broth aliquots were briefly incubated with polyclonal antisera to M. gallisepticum and M. synoviae conjugated with FITC, the same reagents routinely used in the FA technique. The sample was then analyzed by flow cytometry for the association of the fluorescent label and the organism. Samples from inoculated chickens incubated with the homologous antibody-FITC had greater fluorescent intensity than did those incubated with the heterologous antibody-FITC. Diagnosis by flow cytometry was consistent with that by the FA technique except that in one trial one sample was incorrectly identified by flow cytometry as positive for M. gallisepticum, although it was not inoculated with M. gallisepticum. Also, flow cytometry did not correctly identify M. synoviae organisms as readily when broilers were inoculated with both M. gallisepticum and M. synoviae. PMID- 2235828 TI - Locomotion of broiler chickens in floor pens. AB - Locomotion has a major effect on production and animal welfare as it relates to feed and water acquisition, feed utilization, carcass quality, health, and physical vigor. The locomotor abilities of the broiler are also important considerations in pen design and placement of feed and water dispensers. To study the locomotion of broiler chickens and the effect stocking density has on locomotion, eight groups of broiler chickens were observed in an experimental floor pen (1.2 by 1.7 m). A Videomex V Image Motion Computer was used to determine the distance traveled and the frame-by-frame (30 frames per s) location of a focal bird. Four densities (660, 790, 990, and 1320 cm2 per bird) were tested, one on each day of the 4-day recording period for each group of birds. Broiler chickens were active throughout the day and traveled an average distance of 8.8 m per h or 212 m per day. Increasing housing density reduced the distance traveled (10, 8.8, 8.5, and 8.1 m per h for 1,320, 990, 790, and 660 cm2 per bird, respectively) but did not affect the average number of visits to the feeders (4 per h) and water cups (2 per h). The focal birds used the total space provided during the day, indicating that they were not consistently socially restricted to certain areas of the pen. PMID- 2235827 TI - Efficacy of a hydrated sodium calcium aluminosilicate to reduce the toxicity of aflatoxin and T-2 toxin. AB - A hydrated sodium calcium aluminosilicate (HSCAS) was incorporated into diets (.5%) containing 3.5 mg of aflatoxin (AF) per kg and 8.0 mg of T-2 toxin (T-2) per kg, singly, and in combination. Male broiler chicks (n = 480) were provided with feed and water for ad libitum consumption from 1 to 21 days of age. Body weight gains were significantly depressed by AF and T-2, singly, and further decreased by the combination of the two toxins. Efficiency of feed utilization was not affected. The AF alone and the AF plus T-2 combination caused increases in relative liver, kidney, proventriculus, gizzard, spleen, and pancreas weights. Treatment-related changes in hematological and serum biochemical values and enzyme activities were observed. Oral lesions were observed only in chicks receiving the T-2 diets. The HSCAS fed singly did not alter any of the parameters measured but it did diminish the toxicity of AF for many parameters but did not appear to alter the toxicity of T-2. Addition of HSCAS to the AF plus T-2 combination diet diminished some of the effects of the toxin combination. These findings indicate that HSCAS can diminish many of the adverse effects of dietary AF in the chicken, but it has no effect on T-2 toxicity. PMID- 2235829 TI - Immune responsiveness of neonatal chicks and immunocyte precursors from unprimed juvenile chicken donors. AB - The immune responsiveness of immunocyte precursors, obtained from peripheral blood of 4- to 6-wk-old unprimed chickens and assayed with the cell transfer model, was compared with that of neonatal chicks. Little if any splenic plaque forming cell (PFC) production was observed in the spleens of embryonic cell transfer hosts following a single antigen exposure to weak or moderate dosages of mammalian erythrocytes. However, modest to high PFC formation occurred consistently in the hosts following a second exposure to the same antigen when given 3 days later. Although a single immunization failed to elicit PFC formation in embryo hosts, a single injection of a wide range of antigen dosages into 8-day old chicks elicited PFC production consistently. When the double immunization protocol was used with 2- to 9-day-old neonatal chicks, the level of immune responses were indistinguishable from those elicited with a single antigen injection. The difference in the immune kinetics observed in embryo hosts may be related to the embryonic microenvironment, which is permissive, but may not be as immunosupportive as that of neonates. PMID- 2235830 TI - Effects of particle size on the biological availability of calcium and phosphorus in defluorinated phosphate for chicks. AB - A total of 576 d-old, male, broiler chicks were used in two trials 1) to determine the range of Ca and P levels over which the response in bone characteristics is linear and 2) to determine the influence of particle size of defluorinated rock phosphate (DFP) on the bioavailability of Ca and P in DFP. Six treatments were used in Experiment 1 in which varying percentages of added Ca (.00, .06, .12, .24, .36, and .48%) and added P (.00, .05, .10, .20, .30, and .40%) were evaluated in a corn-soybean meal diet containing 23% CP, .47% Ca, and .39% P (.14% available P). Weight gain, feed intake, and tibia breaking strength increased (P less than .001) with increasing levels of dietary Ca and P. Treatments in Experiment 2 consisted of: 1) Diet 1, a corn-soybean meal basal diet (23% CP, .50% Ca, .46% P, .21% available P), 2) Diet 1 with .12% added Ca from calcium carbonate (CC) and .07% added P from monosodium phosphate (MSP), 3) Diet 1 with .24% added Ca from CC and .14% added P from MSP; and 4 to 8), Diet 1 with .24% added Ca and .14% added P from five particle sizes of DFP. Feed intake, weight gain, and tibia breaking strength and ash percentage increased linearly (P less than .01) and feed:gain ratio decreased quadratically (P less than .10) with increasing percentages of added Ca and P in Diets 1 to 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235832 TI - Effect of bambermycins (Flavomycin) in diets for growing turkeys. AB - Two experiments were conducted to investigate the response of turkeys to graded levels of bambermycins++ in wheat-based diets. In one, 960 Medium White poults were fed 0,2,3, or 4 mg bambermycins per kg from day-old to 12 wk of age. In the other, 264 male and 408 female Large White poults were fed 0,2,5, or 10 mg bambermycins per kg from day-old to 15 (females) or 18 (males) wk of age. Response of Medium White poults increased with age, with significantly greater weight gain from 8 to 12 wk of age as well as final weights when the diet was supplemented with bambermycins. Large White poults responded with highly significant increases in gains from 0 to 4 and 4 to 8 wk of age, and a highly significant linear response to bambermycins in final weights. Although feed efficiency of Large White poults from 0 to 4 wk of age increased with bambermycins, overall efficiency in both trials decreased when the diets were supplemented. The earlier and greater response of Large White poults in comparison with birds of a Medium White strain may be related to the differing growth characteristics of those strains. The difference may also be related to the re-use of litter in the former trial. However, the effect of neither strain nor litter was determined within the same experiment. PMID- 2235831 TI - Effect of body weight, feed allowance, and dietary protein intake during the prebreeder period on early reproductive performance of broiler breeder hens. AB - In Experiment 1, two groups (n = 180) of breeder pullets were selected at 16 wk from two larger groups with BW of either 1,591 +/- 43 (LBW) or 1,988 +/- 59 g (HBW). From 16 wk of age until a peak feed allotment of 159 g per bird per day, weekly feed allowances were increased in a low (LOW), medium (MED), or high (HIGH) manner. There were significant differences (P less than .05) in BW between the LBW and HBW treatments through 32 wk of age. Within each pullet weight class, the HIGH treatment was numerically heaviest through 32 wk. The HBW hens had significantly improved hen-day production from 24 to 28 (P less than .001) and 28 to 32 wk (P less than .06). The LOW treatment resulted in significantly poorer production in both the LBW and HBW weight groups from 24 to 28 wk. There were no signficant treatment effects on egg weight at a given age. Within each pullet treatment, the HIGH treatment resulted in an increased percentage of double yolked (DY) eggs from 24 to 28 wk (P less than .05) and 28 to 32 wk (P less than .07). In experiment 2, pullets in each of two pullet treatments received approximately 12 kg of feed from 2 to 24 wk of age. One treatment received a greater quantity of feed early in the rearing period (HEAVY) while pullets in the other treatment received a greater quantity of feed later in the rearing period (LIGHT). One-half of the pullets from each rearing treatment were fed either a 14% (LOWPRO) or 18% (HIGHPRO) protein diet during the prelay period (18 to 24 wk). Pullets in the HEAVY treatment were significantly heavier (P less than .01) than those in the LIGHT treatment at 21 but not at 24 wk. The HIGHPRO treatment resulted in a significant improvement (P less than .05) in hen-day egg production from 24 to 28 and 28 to 32 wk. There were no treatment effects on egg weight, and the LOWPRO treatment resulted in a significant increase (P less than or equal to .01) in the number of DY eggs from 28 to 32 wk. PMID- 2235833 TI - Effects of feeding level during pullet-layer transition and of pretransition lighting on performance of broiler breeders. AB - Four feeding regimens were compared for the pullet-layer transition period and two light types, white and narrow-band green fluorescent, were compared in the grower period to determine their subsequent effects on reproductive performance of broiler breeder hens. Four limit-feeding treatments imposed from 18 wk (body weight of 1.8 kg) to "mature weight" of 2.8 kg at 27 (Treatment 1), 25 (Treatment 2), 24 (Treatment 3) and 22.5 (Treatment 4) wk of age supported weight gains of, respectively, 15, 19, 23, and 27 g per day. Production of total and hatching eggs was similar among all dietary and lighting treatments. Hens given dietary Treatment 1 had a higher production from 224 to 252 days but had a lower production from 168 to 189 days associated with a 2.6-day later age at 50% egg production. Feeding regimen and lighting treatment had no effect on egg weight, and feeding did not affect mortality. Green lighting reduced mortality from 2.0 to 1.4% at 70 to 126 days and from 5.7 to 4.0% from 126 to 280 days of age, compared with white lighting. Fertility was 5% lower for Treatment 4 versus Treatment 1 and 4% lower for white versus green lighting. The advantage of higher initial hatching egg production obtained with rapid growth, of greater than 15 g per day, during the transition period was outweighed by detrimental effects on production and fertility in later periods. Green light may increase chick production per hen housed by causing decreased pullet mortality and increased fertility. PMID- 2235834 TI - Effect of varying calcium and phosphorus level on manganese utilization. AB - Two experiments were conducted to evaluate the effect of varying levels of excess Ca and P on manganese (Mn) utilization. The criterion used to study the Mn antagonizing effects of excess Ca and P was the regression of total tibia Mn on supplemental Mn intake. In Experiment 1, high supplemental levels of Mn were fed (0, 500, and 1,000 mg Mn per kg); in Experiment 2, lower Mn levels were fed (0, 50, and 100 mg Mn per kg). Supplements were added to a corn-soybean meal diet containing 1.1% Ca, .7% (.5% available) P, and 37 mg Mn per kg. In Experiment 1, a 3 x 3 x 3 factorial arrangement of treatments (four replicates) was used. Treatments were as follows: 0, .5, and 1.0% excess Ca as feed-grade ground limestone; 0, .4, and .8% excess P as KH2PO4; and 0, 500, and 1,000 mg Mn per kg as MnSO4.H2O. Total tibia Mn was depressed by P (P less than .0001) but not by Ca (P greater than .05). Compared with the standard (no added P), .4% P reduced Mn utilization by 22%, whereas .8% P reduced it by 38%. Manganese supplementation was found to ameliorate the growth-depressing effect of .8% supplemental P. Results of Experiment 2 agreed with the results in Experiment 1, providing evidence that bioavailability estimates obtained from experiments containing high levels of Mn can be extrapolated to diets containing lower levels. Results from Experiment 2 indicated that, relative to the standard (no added P), .22, .44 and .88% excess P reduced Mn utilization by 16, 22 and 31%, respectively. PMID- 2235835 TI - Lipid metabolism in liver of chicks: response to feeding. AB - Fatty-acid synthase is an enzyme complex responsible for the synthesis of the carbon chain of fatty acids. The hepatic activity of this enzyme increases rapidly during a refeeding period following a fast. The activity of fatty-acid synthase in liver of newly hatched chicks rises in parallel with the activities of other lipogenic enzymes at the initiation of feeding. Cycloheximide, an inhibitor of protein synthesis, prevents the feeding-associated rise of other lipogenic enzymes, but not of fatty-acid synthase. Evidence is reviewed that supports the hypothesis that in fasted chicks as well as in unfed, newly hatched chicks, fatty-acid synthase exists in a catalytically less-active form, one that is activated in response to feeding. PMID- 2235836 TI - Hepatic protein and amino-acid metabolism in poultry. AB - Two subjects are discussed: first, the regulation of hepatic protein synthesis; and second, the intermediary metabolism of methionine, particularly with respect to the role of 2-hydroxy-4-(methylthio)-butanoic acid (HMB, Alimet). In the first section, the regulation of albumin synthesis is reviewed in terms of molecular events associated with the changes in albumin synthesis during fasting and refeeding. The effect of infection or of inflammatory stress on both albumin and total protein synthesis in the liver is also discussed. In the second part, research results are presented which indicate that HMB is a naturally occurring compound in methionine intermediary metabolism. The HMB synthesis by chick liver enzymes is demonstrated, and its role in normal avian methionine metabolism is discussed. PMID- 2235837 TI - Effect of peptide histidine isoleucine on in vitro and in vivo prolactin secretion in the turkey. AB - Studies were conducted both in vitro, using monolayer cultures of turkey pituitary cells, and in vivo, using ovariectomized turkey hens, steroid-primed ovariectomized hens, and immature toms to compared the effectiveness of peptide histidine isoleucine (PHI) with that of vasoactive intestinal peptide (VIP) in stimulating prolactin (PRL) secretion. Vasoactive intestinal peptide, a putative PRL-releasing factor (PRF) in the turkey, was approximately 1000-fold more effective than PHI in stimulating PRL secretion in vitro. Prolactin secretion was significantly enhanced by the exposure of pituitary cells to 10(-7) M PHI and a similar stimulation was observed with 10(-10) M VIP. Injection of cannulated, unrestrained turkeys with PHI at doses up to 100 micrograms per kg of BW caused no significant change in circulating PRL concentrations, but injection of 10 micrograms of VIP per kg resulted in a 7 to 22-fold increase in plasma PRL concentration within 10 to 30 min following injection. These results demonstrate a marked difference between the turkey and the rat in their response to a PRL stimulating neuropeptide. In contrast to what was observed in the turkey, PHI is a strong PRF in the rat, with a potency equal to or greater than that of VIP. Earlier studies have shown that thyrotropin-releasing hormone, another strong PRF in mammals, has little consistent PRF activity in the turkey. Thus, the present studies add additional evidence of major differences between mammals and birds in the control of PRL secretion by hypothalamic neuropeptides. PMID- 2235838 TI - The effect of tamoxifen on semen fertilization capacity in White Leghorn male chicks. AB - Tamoxifen (TAM) is an antiestrogen that advances sexual puberty in cockerels, turkey toms, and Muscovy drakes. The effect of TAM on semen-fertilization capacity in White Leghorn (WL) male chicks was assayed in the present study. Sixty, 2-wk-old, male chicks were divided into two equal groups. The chicks from one group were injected im with 1 mg of TAM per kg of BW every other day; those from the second group were vehicle-treated (with corn oil) and served as controls. Each chick was paired with a virgin, WL laying hen. When semen was produced, the paired female was inseminated twice a week. The results revealed that TAM administration caused the early production of fertile semen, which resulted in the first normal descendants as early as 8 wk of age and brought about 100% of parenthood by the age of 88 days. PMID- 2235840 TI - Head skeletal abnormalities associated with the throat tuft mutation (hfdTt) in the Japanese quail. AB - Hereditary abnormalities of head skeleton ascribed to embryonic visceral arch defects were investigated in Japanese quail homozygous for the throat tuft mutation (hfdTt). Differential staining for bone and cartilage of 15-day embryos revealed partial deletion or irregularity in the mandible, basiparasphenoid, hyoid apparatus, and quadratojugal bones, incidences of which were 84, 44, 40, and 18%, respectively. Incidence of the head-skeleton abnormality was 88% when individuals having at least one of the abnormalities mentioned were regarded as abnormal. Throat tuft (hfdTt) and ear tuft (hfd) homozygotes showed distinct differences between them, although both alleles are associated with visceral arch defects. PMID- 2235839 TI - Conditions necessary for a response by the commercial laying hen to supplemental choline and sulfate. AB - An experiment was conducted with commercial laying hens, 24 wk of age, to study the response from adding 440 mg of choline and sulfate as 2 g of K2SO4 per kg of a corn soybean-meal diet containing different levels of supplemental DL-Met. The basal diet was formulated to be deficient (.495%) in sulfur amino acids, and nonsulfate forms of trace minerals were used in all diets. The experiment was conducted for 22 wk; however, only the data from the last 12 wk were used as the measurement of response since the responses were greatest during this period. Egg production, egg weight, and feed efficiency were improved with each addition of Met from 0 to .2%. Choline supplementation of the diet containing added .033% Met significantly increased egg production. However, no response was obtained from choline supplementation of diets containing 0 or .067% added Met. Addition of sulfate improved egg production when it was added to the diet with choline but not when it was added to the diet with Met. PMID- 2235841 TI - Influence of dietary supplementation with Streptococcus faecium M-74 on broiler body weight, feed conversion, carcass characteristics, and intestinal microbial colonization. AB - Two experiments were conducted to determine the influence of Streptococcus faecium M-74 supplementation of broiler diets. Mixed-sex or male only chicks were used in the experiments. Both experiments consisted of six dietary treatments and four replicates per treatment in a randomized block design. The S. faecium was fed alone for 21, 36, or 44 days or for 44 days with S. faecium supplemented in the water for the first 14 days. In another treatment, S. faecium was fed for 44 days, but the feed was restricted for Days 8 through 13. The S. faecium was also fed in combination with antibacterial products (AP) for 44 days. An additional diet was an unsupplemented basal, and another was supplemented only with AP. In Experiment 1, feed efficiency was significantly better with the basal and diets supplemented with S. faecium than with those diets supplemented with AP or AP and S. faecium. In Experiment 2, BW of broilers at 44 days of age were significantly heavier for broilers receiving S. faecium in the feed and also S. faecium in the water for the first 14 days as compared with broilers receiving AP or AP and S. faecium supplementation. There were no significant differences in carcass yield or composition characteristics. In Experiment 1, the scores representing S. faecium colonies found in the intestinal tract were not influenced by dietary treatment. The ceca had the highest S. faecium score of any of the intestinal tract locations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235842 TI - Effects of feeding lasalocid on performance of broilers in moderate and hot temperature regimens. AB - Three trials were conducted in environmental chambers to study the effects of feeding lasalocid on broiler performance. Birds were randomly assigned at 31 or 35 days of age to one of four treatment groups: hot cyclic (26.7 to 37.8 C and 90 to 40% RH) with basal diet; hot cyclic with lasalocid diet (88 mg/kg); moderate constant (21 C and 50% RH) with basal diet; or moderate constant with lasalocid diet. All birds were killed and processed 2 wk after the start of each trial. Percentage of carcass yield and fat pad weight were determined. In the moderate temperature regimen, lasalocid feeding caused a depression in the 2nd wk gain (469 versus 486 g) but not in the final 2-wk gain. In the hot temperature regimen, birds fed lasalocid gained significantly more weight in the 2nd wk than those fed the basal diet (341 g versus 325 g) and had a significantly better feed conversion in the 2nd wk (2.04 versus 2.61) and overall (2.07 versus 2.32) than those fed the basal diet. PMID- 2235843 TI - Use of ivermectin to control the lesser mealworm (Coleoptera: Tenebrionidae) in a simulated poultry broiler house. AB - Broiler chickens were fed ivermectin at a level of 2 ppm for 5 wk to determine its efficacy against the lesser mealworm, Alphitobius diaperinus. This treatment essentially eliminated lesser mealworm larvae; no ivermectin residues were found in the livers of the treated chickens, even without a withdrawal period. However, the feeding of ivermectin may reduce body weights body weight gain and feed efficiency at older ages. PMID- 2235844 TI - Dietary and monensin effects on activity of hepatic microsomal mixed function oxidase system in chickens. AB - Four experiments were conducted to investigate if the degree of activation of the microsomal mixed-function oxidase (MFO) system was related to the degree of growth depression associated with the addition of monensin to the diet. The experiments were conducted with broiler chicks in battery brooders in which the chicks were fed diets of various composition and containing monensin at 0 to 160 ppm. In all experiments, the activity of the MFO system was estimated by the change in the content of cytochrome P-450 in the hepatic microsomes. Activities of some microsomal enzymes were also measured in some of the experiments. Feeding a diet with 24% protein containing fish meal, alfalfa meal, and torula yeast significantly increased the activity of the MFO system in comparison with feeding an isonitrogenous and isoenergetic corn and soybean diet, but there was no difference between the diets in the toxicity of monensin as measured by growth rate. Supplementing a 16% protein but not a 24% protein diet with monensin significantly reduced growth rate. In none of the four experiments was there a statistically significant change in the hepatic content of cytochrome P-450 as a result of feeding monensin. Thus, variation in the magnitude of growth depression caused by monensin in diets of different protein concentration or ingredient composition does not appear to be explained on the relative degree of the activation of the MFO system. PMID- 2235845 TI - Glucocorticoid activation of deoxyribonucleic acid degradation in bursal lymphocytes. AB - Treatment of animals with exogenous adrenal steroids or elevation of endogenous glucocorticoids results in a profound involution of lymphoid tissue. In rodent species, this lymphoinvolution is accompanied by lymphocyte cell death and extensive degradation of the genome prior to lymphocytolysis. In the present study, this process was investigated in the bursa of Fabricius of domestic fowl. Four-wk-old chicks were treated with a single injection of dexamethasone, and bursal regression and cell viability were monitored over a 72-h period. Following hormone treatment, DNA was extracted from bursal lymphocytes and analyzed by agarose gel electrophoresis. Dexamethasone treatment resulted in a rapid regression of bursal tissue that could be detected as soon as 6 h posttreatment, but lymphocyte viability was not altered until 24 h afterward. The DNA isolated from bursal lymphocytes of glucocorticoid-treated birds appeared to be degraded at internucleosomal sites and generated a "ladder" of discrete DNA fragments when analyzed by agarose gel electrophoresis. This form of hormone-induced cell death, referred to as programmed cell death, may play a key role in glucocorticoid mediated immunosuppression. PMID- 2235846 TI - Effect of dietary protein source and cereal type on the incidence of sudden death syndrome in broiler chickens. AB - Three experiments were conducted to compare the incidence of Sudden Death Syndrome (SDS) in male Peterson by Arbor Acre broiler chickens fed diets with either corn or wheat as the grain type and meat meal or soybean meal as the main protein source. In the first two experiments, the broilers were raised in floor pens to 6 wk of age, and in the third experiment they were raised in battery brooder cages to 4 wk of age. In both floor pen studies, total mortality and the incidence of SDS were significantly higher for wheat-fed birds, while SDS as a percentage of total mortality was not affected by cereal type. In the brooder study, neither total mortality nor mortality from SDS was significantly affected by cereal type. In the floor pen studies, the incidence of SDS as a percentage of the birds housed, was reduced by the inclusion of meat meal in the diet. In the brooder study, total mortality and the incidence of SDS were not affected by protein source, but SDS as a percentage of total mortality was reduced with the inclusion of meat meal in the diet. PMID- 2235847 TI - Energy metabolism of broiler breeder hens. 1. The partition of dietary energy intake. AB - The partitioning of AME intake (MEI) and recovered energy (RE; defined as MEI minus heat production) was investigated on Hubbard broiler-breeder hens (BB) by using indirect calorimetry and energy balance. The regression of RE on MEI was linear (R2 = .96; P less than .01) with a slope of .817 +/- .024 (SE) and a y intercept of -238.3 +/- 10.7 (SE). The maintenance energy requirement was 292 kilojoule (kJ) per kg per day (367 kJ per kg.75 per day). The regression of body RE, defined as RE minus egg energy, on MEI was linear (R2 = .96; P less than .01) with a slope of .799 +/- .045 (SE) and a y-intercept of -344.9 +/- 19.7 (SE). Therefore, an MEI of 432 kJ per kg per day was required by BB hens to maintain body energy equilibrium when they were laying at approximately 85% production. At an MEI of less than 432 kJ per kg per day, body energy was used for egg production. The AME cost of depositing 1 kJ of body, egg, protein, or fat energy was (mean +/- SE) 1.21 +/- .06, 91 +/- .32, 1.96 +/- .71, and 1.05 +/- .15 kJ, respectively. The results indicate that individually caged BB hens between 28 and 36 wk of age in a thermal-neutral environment (21 C) require approximately 1.6 megajoule (MJ) of AME per bird per day for normal growth (3 g/per day) and egg production (85%). PMID- 2235848 TI - Energy metabolism of broiler breeder hens. 2. Contribution of tissues to total heat production in fed and fasted hens. AB - In vitro rates of O2 consumption were investigated using excised biopsies from the liver, ileum, magnum, and latissimus dorsi muscle of Hubbard (H) broiler breeder hens fed four levels of ME intake. Diet had no effect on O2 consumption of any tissue. The overall mean initial O2 consumption (microL of O2 per mg of dry weight per h) for latissimus dorsi, liver, ileum, and magnum tissues were 4.38, 13.33, 10.54, and 8.01, respectively. The Na+ and K(+)-adenosine triphosphatase-dependent respiration (ouabain-sensitive respiration) was 16% of the initial rate for latissimus dorsi, liver, and magnum tissues and 22% for ileum tissues. Fasting heat production of H and Arbor Acre (AA) meat-type hens measured over 3 days following an initial 24-h fast was 219 and 216 kilojoules (kJ) per kg per day (1 kJ = .239 kcal). There were no strain differences in the partitioning of O2 consumption into tissue components of fasted H and AA hens. Fasting metabolism accounted for 75% of the maintenance energy requirement in the hens. The liver, gut, and reproductive tract, which together make up 5 to 6% of BW, account for 26 and 30% of the total energy expenditure in fed and fasted hens, respectively. PMID- 2235849 TI - Riboflavin requirement of chicks fed purified amino acid and conventional corn soybean meal diets. AB - Three experiments were conducted to determine the riboflavin requirement for maximal growth of young chicks. Graded levels of crystalline riboflavin were added to either riboflavin-free, purified amino acid diets or corn-soybean meal diets. Chick growth responses were obtained upon adding riboflavin to both diets. Chicks fed the purified diet required 1.8 mg of riboflavin per kg of diet, but those fed the corn-soybean meal diet required 2.63 mg of riboflavin per kg of diet. Retarded growth and leg paralysis, rather than curled-toe paralysis, were the predominant signs of riboflavin deficiency. Calculations suggested that riboflavin bioavailability in the corn-soybean meal diet was 59.1%. PMID- 2235850 TI - High performance liquid chromatographic analysis of the malondialdehyde content of chicken liver. AB - An assay for the determination of malondialdehyde (MDA) levels in chicken liver is described. The method involves the extraction of the tissues with trichloracetic acid and reaction of the extract with TBA. The reaction mixture is then purified using reverse-phase cartridges and the TBA-MDA reaction products are separated from other TBA-reactive substances by reverse-phase HPLC. The method is rapid, reproducible, easy to perform, and is sensitive in the nanogram (10(-11) mol) range. Application of this technique may be useful to determine the extent of lipid peroxidation occurring in the liver as a result of degenerative liver diseases or poisoning with certain hepatotoxins. PMID- 2235851 TI - Arginine requirement of starting broiler chicks. AB - Three experiments were conducted to estimate the arginine requirement of male broiler chicks from 0 to 3 wk of age. The experiments were conducted in battery brooders with wires floors, and the birds received water and feed ad libitum. In the first experiment, chicks were fed a diet based on corn, soybean meal, casein, and corn-gluten meal containing 3,200 kcal ME per kg and either 20 or 23% crude protein. Regression analysis indicated an arginine requirement of 1.22% for maximum growth rate and feed efficiency with the 20% protein diet. For chicks fed the 23% protein diet, neither growth rate nor feed efficiency was significantly different among the diets containing arginine ranging from 1.13 to 1.43%. In the second experiment, a basal diet was used containing 17.5% casein and 22.5% protein with arginine ranging from 1.03 to 1.43%. An arginine requirement of 1.18% for maximum body weight gain was estimated by regression analysis, but no significant response to arginine above the basal level was observed for feed efficiency. Performance of chicks fed the basal diet was somewhat reduced because of a difficulty with adherence of feed to the beaks. In a third experiment, three basal diets containing 21, 22, or 23% protein were formulated from practical ingredients without use of casein. The requirement for maximum growth rate and feed efficiency was estimated to be 1.24 to 1.28% for the three diets. The results of these investigations indicate that the arginine requirement for starting chicks suggested by the National Research Council in 1984 of 1.44% in diets containing 3,200 kcal ME per kg is too high for practical diets. The data presented here support an arginine requirement of 1.25%. PMID- 2235852 TI - The role of plasma thyroid hormones in the regulation of body weight of single comb White Leghorn and broiler embryos. AB - Studies were conducted to determine if sex differences in embryo weights existed in a light-weight breed of chickens (the Single Comb White Leghorn, SCWL) and in a heavy broiler strain of chickens. Plasma thyroid hormone concentration was measured to determine its relationship to embryo weight. Male SCWL embryos were heavier than females at 15 and 17 days of incubation, but not at 13 days. Male broiler embryos were heavier than females at 13 and 15 days of incubation, but not at 17 days. There was no sex difference in the levels of plasma triiodothyronine (T3) or of tetraiodothyronine (T4) of SCWL embryos at those respective ages. The plasma T4 in male broiler embryos was significantly lower than that in the females at 15 and 17 days of incubation, but not at 13 days. There was no relationship between plasma T3, and the weight of SCWL embryos. There were significant linear regressions of embryo weight on the plasma T4 levels for SCWL males at 13 and 15 days of incubation and for SCWL females at 13 and 17 days of incubation, respectively. A significant regression of embryo weight on plasma T4 was found in female broiler embryos at 13 days of age, but not in females at other ages or in males at any of the ages studied. PMID- 2235853 TI - The effect of age of breeder hens on residual yolk fat, and serum glucose and triglyceride concentrations of day-old broiler chicks. AB - The fat content and the concentrations of glucose and triglyceride in day-old chicks hatched from 27 and 60 wk-old broiler-breeder hens were determined from pooled samples of residual yolk and blood serum, respectively. Serum glucose and triglyceride levels were unaffected (P greater than .05) by breeder age, although there was a linear (P less than .001; r = .67) relationship between these characteristics and chick weight. Yolk fat, adjusted for chick weight, was on the average 13% greater (P less than .05) in chicks from old breeders than chicks from young breeder hens. Yolk wet weight was not affected (P greater than .05) by breeder age. Results indicate that breeder age may affect chick performance through alterations in the fat content of residual yolk. PMID- 2235854 TI - Effect of the sex-linked dwarfing gene (dw) upon skeletal development of young broiler chicks. AB - The influence of the sex-linked dwarfing gene (dw) on growth and skeletal development in young male broiler chicks was investigated. Chickens that were homozygous (dw/dw) for the dwarfing gene had significantly lower BW and tibiotarsus lengths when compared with the heterozygous (Dw/dw) or normal (Dw/Dw) genotypes. All genotypes exhibited similar incidences of tibial dyschondroplasia. In contrast to several other types of dwarfism, there was no effect of the dw gene on the width of the epiphyseal growth plate or the proteoglycan content of this tissue. PMID- 2235855 TI - A comparison of seven microbiological sampling procedures for hard-cooked eggs. AB - Seven microbiological sampling methods for hard-cooked eggs were evaluated and compared. Fresh eggs within 24 h of oviposition were cooked at 98 C for 22 min in water and then cooled in 31 C water. Eggs were dipped for 10 min in a physiological saline solution (.85% saline) 10 C cooler than the eggs and containing known numbers of bacteria. Eggs were then stored for 4 days at 6 C and sampled using one of seven rinse or blend procedures on whole eggs, shell, shelled egg contents, or shelled egg contents plus shell. Highest recoveries were made from the peeled egg plus shell rinse, shell rinse, whole egg blend, and shell blend. Lowest recoveries were found with the whole egg rinse, the peeled egg rinse, and the peeled egg blend. These results indicate that significant numbers of organisms are associated with the inner and outer shell surfaces as well as the egg contents surface (albumen). Satisfactory recoveries can be made with the peeled egg plus shell rinse or the whole egg blend. Whole egg rinsing of hard-cooked eggs does not appear to be satisfactory. PMID- 2235856 TI - Suspected child sexual abuse. PMID- 2235857 TI - Suspected keratoacanthoma--a wolf in sheep's clothing? PMID- 2235859 TI - Bleeding in pregnancy. PMID- 2235858 TI - The breathless child. PMID- 2235860 TI - Psychiatric night calls. PMID- 2235861 TI - The acute abdomen. PMID- 2235862 TI - Collapse--on the spot management. PMID- 2235863 TI - TWAR and changing respiratory infections. PMID- 2235864 TI - Dave's return. PMID- 2235865 TI - The care of hypertensive patients. PMID- 2235866 TI - Adolescent bone tumours. PMID- 2235867 TI - Revision strategies. PMID- 2235868 TI - The asthmatic child. PMID- 2235869 TI - The returning traveller. PMID- 2235870 TI - Management of travellers' diarrhoea. PMID- 2235871 TI - Imported malaria. PMID- 2235872 TI - Parasitic diseases. PMID- 2235873 TI - Sexually transmitted diseases. PMID- 2235874 TI - Pharmacists and GP prescribing. PMID- 2235875 TI - Chemical pathways of peptide degradation. III. Effect of primary sequence on the pathways of deamidation of asparaginyl residues in hexapeptides. AB - Deamidation of Asn residues can occur either by direct hydrolysis of the Asn residue or via a cyclic imide intermediate. The effects of primary sequence on the pathways of deamidation of Asn residues were studied using Val-Tyr-X-Asn-Y Ala hexapeptides with substitution on the C-terminal side (Y) and on the N terminal side (X) of the Asn residue. In acidic media the peptides deamidate by direct hydrolysis of the Asn residue to yield only Asp peptides, whereas under neutral or alkaline conditions, the peptides deamidate by formation of the cyclic imide intermediates which hydrolyze to yield both isoAsp and Asp peptides. At neutral to alkaline pH's the rate of deamidation was significantly affected by the size of the amino acid on the C-terminal side of the Asn residue. The amino acid on the C-terminal side of the Asn residue has no effect on the rate of deamidation at acidic pH. Changes in the structure of the amino acid on the N terminal side of the Asn residue had no significant effect on the rate of deamidation at all the pH's studied. For peptides that underwent deamidation slowly, a reaction involving the attack of the Asn side chain on the peptide carbonyl carbon resulting in peptide bond cleavage was also observed. PMID- 2235876 TI - Stereochemical characterization of the diastereomers of the amobarbital N glucosides excreted in human urine. AB - The stereochemistry associated with the amobarbital N-glucoside diastereomers (1a and 1b) that are excreted by humans in urine is unknown. Using X-ray crystallography, the absolute configuration of 1b was determined to be S (C-5 position of the barbiturate ring). Following oral administration of amobarbital to Caucasians and Orientals, from 5 to 25% of the dose of amobarbital was excreted in the urine as 1b. The other diastereomer, 1a, accounted for less than 0.1 to 0.2% of the dose in four individuals, with none detected in nine individuals. The rate constants, kf,1b, determined from the urinary excretion of 1b were lower than those previously reported for unresolved amobarbital N glucosides. However, based on the urinary excretion of 1b, the rate constants, K, for elimination of amobarbital in Caucasians and Orientals were similar to those previously determined from the serum levels of amobarbital and the urinary excretion of unresolved amobarbital N-glucosides. In previous studies of the N glucosylation of amobarbital, it is likely that a single N-glucose diastereomer, 1b, was being observed. PMID- 2235877 TI - An electrotopological-state index for atoms in molecules. AB - A new method for molecular structure description is presented in which both electronic and topological characteristics are combined. The method makes use of the hydrogen-suppressed graph to represent the structure. The focus of the method is on the individual atoms and hydride groups of the molecular skeleton. An intrinsic atom value is assigned to each atom as I = (delta v + 1)/delta, in which delta v and delta are the counts of valence and sigma electrons of atoms associated with the molecular skeleton. The electrotopological-state value, Si, for skeletal atom i is defined as Si = Ii + delta Ii, for second row atoms, where the influence of atom j on atom i, delta Ii, is given as sigma(Ii-Ij)/rij2; rij is the graph separation between atom i and atom j, counted as the number of atoms. The characteristics of the electrotopological state values are indicated by examples of various types of organic structures, including chain lengthening, branching, heteroatoms, and unsaturation. The relation of the E-state value to NMR chemical shift is investigated for a series of alkyl ethers. The E-state oxygen value gives an excellent correlation with the 17O NMR: r = 0.993 for 10 ethers. A biological application of the E-state values in QSAR analysis is given for the binding of barbiturates to beta-cyclodextrin. PMID- 2235878 TI - The molecular weight dependence of nasal absorption: the effect of absorption enhancers. AB - A series of polyethylene glycols (PEGs) ranging in molecular weight from near 600 to over 2000 daltons was used to study the effects of three absorption enhancers (sodium glycocholate, sodium lauryl sulfate, and polyoxyethylene 9 lauryl ether) on the molecular weight permeability profile of the nasal mucosa of the rat. Molecular weight-permeability properties were studied both by following changes in the excretion of the polyethylene glycols as a function of their molecular size and by examining the nasal mucosa for morphologic changes following exposure to the PEG/enhancer mixtures. Each absorption enhancer was found to affect the mucosa and its permeability in a unique manner. At a 1% concentration, sodium glycocholate only slightly affects tissue morphology and does not significantly alter the molecular weight permeability profile of the mucosa. In contrast, 1% sodium lauryl sulfate causes severe alteration of the mucosa and also greatly increases the absorption of both the PEG 600 and the PEG 2000 oligomers. Polyoxyethylene 9 lauryl ether was found to exert its action in a concentration dependent manner. At a concentration of 0.1%, few changes were seen in either mucosal integrity or permeability. At a 1% concentration, however, a significant alteration in the structure of the mucosal tissues as well as a profound increase in the permeability of the mucosa to the PEGs was observed. Correlation of mucosal integrity with the effectiveness of an enhancer indicates that some of these compounds appear to be acting by altering the structure of the mucosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235879 TI - Biochemical and mechanical characterization of enzyme-digestible hydrogels. AB - Albumin-cross-linked hydrogels were prepared by free radical polymerization using 1-vinyl-2-pyrrolidinone as a monomer and functionalized albumin as a crosslinking agent. The degree of chemical cross-linking was controlled by varying the degree of albumin functionality and the concentration of albumin. With emphasis placed on the potential use of these hydrogels for long-term oral drug delivery, gel characterization studies examined both the swelling and the mechanical properties in the absence and presence of pepsin. In the absence of pepsin, the equilibrium swelling ratio in simulated gastric fluid ranged from 17 to 55, depending on the degree of albumin functionality and the albumin concentration. Swelling was pH dependent at pH's greater than 7. The uptake of solvent into the dried hydrogels was determined to be Fickian. The integrity of swelling gels was dependent on the concentration of the functionalized albumin as well as on the degree of albumin functionality. In the presence of pepsin, a predominance of either surface or bulk degradation was observed, depending on the functionality of the albumin used as a cross-linker. Gel integrity during pepsin degradation also showed a marked dependence on the albumin functionality. PMID- 2235880 TI - Percutaneous penetration enhancement in vivo measured by attenuated total reflectance infrared spectroscopy. AB - A novel application of attenuated total reflectance IR spectroscopy (ATR-IR) was used to monitor the outer several microns of the stratum corneum (SC) and, thereby, demonstrate enhanced percutaneous absorption in vivo in man. 4 Cyanophenol (CP) as a model permeant yielded a unique IR signal, distinct from those of the stratum corneum and the vehicle components. CP was administered for 1, 2, or 3 hr as a 10% (w/v) solution either in propylene glycol or in propylene glycol containing 5% (v/v) oleic acid. The absorbance at 2230 cm-1, which corresponded to C identical to N bond stretching, diminished significantly faster when CP was codelivered with oleic acid. An IR absorbance due primarily to propylene glycol at 1040 cm-1 (C-O stretching) also disappeared more quickly following application of the enhancer-containing solution. In addition, only the formulations with oleic acid induced a higher wavenumber shift in the frequency of the asymmetric C-H bond stretching absorbance. This change indicates increased lipid-chain disorder, the mechanism by which oleic acid is believed to cause enhanced drug transport across the stratum corneum. Therefore, ATR-IR permits one to examine noninvasively the kinetics, extent, and mechanism of percutaneous penetration enhancement in vivo in human subjects. PMID- 2235881 TI - A method for quantifying particle absorption from the small intestine of the mouse. AB - We have developed a method for quantifying the absorption of model fluorescent latex particles from the mouse small intestine into Peyer's patches, mesenteric lymph nodes, and spleen. The procedure combines a simple and exhaustive particle recovery technique with a highly sensitive particle counting technique. Mice were orally gavaged with fluorescent polystyrene latex suspensions, and at various time points Peyer's patches, normal absorptive small intestinal tissue, mesenteric lymph nodes, and spleen were collected. The tissue samples were solubilized using an aqueous potassium hydroxide and surfactant solution and particles were counted using a flow cytometer. Using this method we were able to detect and quantify small numbers of particles, measure the course of uptake and clearance, and determine the tissue distribution of absorbed particles. Data generated using this technique indicate that particle absorption depends on the dose level, particle size, and fed state of the animals. PMID- 2235882 TI - Thermodynamics and mathematical modeling of the partitioning of chlorpromazine between n-octanol and aqueous buffer. AB - The distribution of chlorpromazine (CPZ) between aqueous buffer solutions and 1 octanol was studied over a wide range of pH, buffer concentration, and temperature. A mathematical model was developed to simulate the distribution profiles. It is assumed that only monomers of CPZ exist in the organic phase, whereas in the aqueous phase, association equilibria were assumed to occur. The model predicted the formation of dimers and no higher aggregates over most of the concentration range covered in this study. Thermodynamic parameters for the partition equilibria were evaluated from the equilibrium partition coefficients measured as a function of temperature. Positive values of delta H and delta S were obtained for the transfer of CPZ from the aqueous to the organic phase. The process is entropy controlled indicative of a hydrophobic interaction between CPZ and the aqueous solvent. PMID- 2235883 TI - Absorption of polyethylene glycols 600 through 2000: the molecular weight dependence of gastrointestinal and nasal absorption. AB - Polyethylene glycols (PEGs) 600, 1000, and 2000 were used to study the molecular weight permeability dependence in the rat nasal and gastrointestinal mucosa. Absorption of the PEGs was measured by following their urinary excretion over a 6 hr collection period. HPLC methods were used to separate and quantitate the individual oligomeric species present in the PEG samples. The permeabilities of both the gastrointestinal and the nasal mucosae exhibited similar molecular weight dependencies. The steepest absorption dependence for both mucosae occurs with the oligomers of PEG 600, where the extent of absorption decreases from approximately 60% to near 30% over a molecular weight range of less than 300 daltons. Differences in the absorption characteristics between the two sites appear in the molecular weight range spanned by PEG 1000. For these oligomers, the mean absorption from the nasal cavity is approximately 14%, while that from the gastrointestinal tract is only 9%. For PEG 2000, mean absorption decreases to 4% following intranasal application and below 2% following gastrointestinal administration. Within the PEG 1000 and 2000 samples, however, very little molecular weight dependency is seen among the oligomers. In the range studied, a distinct molecular weight cutoff was not apparent at either site. PMID- 2235885 TI - Performance of diltiazem tablet and multiparticulate osmotic formulations in the dog. AB - The in vivo performance of two extended-release (ER) osmotic formulations of diltiazem were evaluated in the beagle dog. Both ER formulations had similar bioavailabilities (F) as the diltiazem solution. Although F was somewhat variable following ER administration, this variability may be related to the drug entity since intra- and interanimal variability of orally administered diltiazem solutions was substantial. Deconvolution of the ER plasma diltiazem data with absorption data from the orally administered diltiazem solutions provided an estimate of the in vivo drug release from the ER formulations. The two ER formulations, designed with different in vitro release profiles, reflected these differences in vivo, with nearly identical respective in vivo and in vitro release profiles. PMID- 2235884 TI - Beta-cyclodextrin/steroid complexation: effect of steroid structure on association equilibria. AB - Molecular associations of beta-cyclodextrin (beta-CyD) with four steroids (cortisone, hydrocortisone, progesterone, and testosterone) have been studied using phase-solubility and spectroscopic techniques. Phase solubility diagrams could be categorized as B type. The complexes are formed at the stoichiometric ratios of 1:2 (drug:beta-CyD). A mathematical model has been proposed to calculate the apparent stability constants. The results suggest that the inclusion of a steroid molecule into the first beta-CyD cavity is thermodynamically more favorable over the association of 1:1 complex with the second beta-CyD molecule except for cortisone, which exhibits anomalous behavior. A mechanism of complexation has been proposed based on the apparent stability constants and chemical structures of the steroids and beta-CyD. It suggests that complexation is first brought about by inclusion of the five-member cyclopentane ring of the steroid molecule into the first beta-CyD cavity. The 1:1 complex subsequently binds with the second beta-CyD to form the 1:2 complex. The association constants of steroid/beta-CyD complexes are of the following order: progesterone greater than cortisone greater than testosterone greater than hydrocortisone. The order of aqueous solubilities of the complexes is hydrocortisone greater than cortisone greater than testosterone greater than progesterone. PMID- 2235886 TI - A redox-based system that enhances delivery of estradiol to the brain: pharmacokinetic evaluation in the dog. AB - The pharmacokinetics of a dihydropyridine-pyridinium salt-type chemical delivery system (CDS) for brain-targeted delivery of estradiol (E2) were examined in dogs. Parameters evaluated in vitro included stability in buffers and biological fluids and plasma protein binding. In vivo studies examined drug and metabolite concentrations in plasma, urine, and cerebrospinal fluid as well as in selected brain regions. The administered lipophilic E2-CDS disappeared very quickly from plasma and was not detected in urine. The oxidized drug form, E2-Q+, was excreted unchanged or as a conjugate in the urine for as long as 2 weeks. Plasma levels were below assay detection limits at later times. Pharmacokinetic analysis of urine E2-Q+ levels allowed estimation of a half-life of 2.2 days. Amounts of E2 Q+ excreted into the urine were proportional to the dose but averaged only 13.9% of the dose, indicating that other routes of excretion must be considered. CSF levels were below the limit of detection for both E2-CDS and E2-Q+, however, brain tissue concentrations of E2-Q+ were similar in several brain regions of individual animals examined 1 or 3 days after drug dosing. PMID- 2235887 TI - Diffusion in porous materials above the percolation threshold. AB - The diffusion of water-soluble solutes in water-soaked porous media was studied by following the release of benzoic acid from poly(vinyl stearate) matrices. The results were analyzed using a pseudo-steady-state diffusion model coupled with the fundamental concepts of percolation theory. The results of the study indicated that the relationship between the bulk diffusion coefficient of benzoic acid in the polymer matrix and the porosity was well described by percolation scaling laws. A very low percolation threshold (0.07) was experimentally observed for this system. PMID- 2235888 TI - Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa. AB - Human colon adenocarcinoma (Caco-2) cells, when grown on semipermeable filters, spontaneously differentiate in culture to form confluent monolayers which both structurally and functionally resemble the small intestinal epithelium. Because of this property they show promise as a simple, in vitro model for the study of drug absorption and metabolism during absorption in the intestinal mucosa. In the present study, the transport of several model solutes across Caco-2 cell monolayers grown in the Transwell diffusion cell system was examined. Maximum transport rates were found for the actively transported substance glucose and the lipophilic solutes testosterone and salicyclic acid. Slower rates were observed for urea, hippurate, and saliylate anions and were correlated with the apparent partition coefficient of the solute. These results are similar to what is found with the same compounds in other, in vivo absorption model systems. It is concluded that the Caco-2 cell system may give useful predictions concerning the oral absorption potential of new drug substances. PMID- 2235889 TI - Determination of solute-polymer interaction properties and their application to parenteral product container compatibility evaluations. AB - Kinetic and thermodynamic interaction properties between dialkyl phthalate test compounds and a polyolefin polymer were examined via a permeation-cell experimental design. Disappearance and appearance rates of solute in the receptor and donor solutions, as well as the equilibrium composition of the test system, are used to determine sorption and diffusion coefficients and the solute/polymer equilibrium binding constant. Sorption rate constants and diffusion coefficients exhibit Arrenhius-type behavior. The binding constants obtained correlate well with the solute's octanol-water partition coefficient. The kinetic and thermodynamic data generated combine with proposed interaction models to identify solute/polymer interactions (binding and leaching) pertinent to evaluating container/solution compatibility for parenteral products. PMID- 2235890 TI - Synthesis and calcium channel antagonist activity of 3-arylmethyl 5-isopropyl 1,4 dihydro-2,6-dimethyl-4-(pyridyl)-3,5-pyridinedicarboxylates. AB - Unsymmetrical aryl(heteroaryl)methyl isopropyl ester analogues of nifedipine, in which the 2-nitrophenyl group at C-4 is replaced by a 2- or 3-pyridyl substituent, were synthesized and evaluated as calcium-channel antagonists using guinea pig ileal longitudinal smooth muscle. The point of attachment of the C-4 pyridyl substituent was a determinant of activity where the relative potency order was 2-pyridyl greater than 3-pyridyl. Within the C-4 2-pyridyl series of compounds, and electronegative substituent such as a trifluoromethyl or bromo at the 4 position of the benzyl ester substituent or a nitrogen atom at the 1 position of a 4-pyridylmethyl ester substituent, enhanced activity relative to the unsubstituted benzyl ester analogue. In contrast, in the C-4 3-pyridyl class of compounds, a variety of aryl(heteroaryl)methyl ester substituents did not alter potency to any significant extent. A number of compounds in the C-4 2 pyridyl series possessing 4-pyridylmethyl, 4-trifluoromethylbenzyl, 4 bromobenzyl, and 3-pyridylmethyl ester substituents were approximately equipotent to nifedipine. The aryl(heteroaryl)methyl ester and C-4 2-pyridyl substituents therefore appear to provide important interdependent contributions to calcium channel antagonist activity. PMID- 2235891 TI - Structure elucidation and thermospray high-performance liquid chromatography/mass spectroscopy (HPLC/MS) of the microbial and mammalian metabolites of the antimalarial arteether. AB - Microbial metabolism studies of the antimalarial drug arteether (1) have shown that arteether is metabolized to six new metabolites in addition to those previously reported (3). Large-scale fermentations with Cunninghamella elegans (ATCC 9245) and Streptomyces lavendulae (L-105) have resulted in the characterization of these metabolites primarily by two-dimensional nuclear magnetic resonance (2D-NMR) methods as 9 beta-hydroxyarteether (2), a ring rearrangement metabolite (3), 3 alpha-hydroxy-11-epi-deoxydihydroartemisinin (4), 9 alpha-hydroxyarteether (5), 2 alpha-hydroxyarteether (6), and 14 hydroxyarteether (7). Thermospray mass spectroscopy/high-performance liquid chromatographic analyses have shown that four of these metabolites (2, 5, 6, 7) are also present in rat liver microsome preparations. PMID- 2235892 TI - Influence of average molecular weights of poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 on phase separation and in vitro drug release from microspheres. AB - The phase separation of fractionated poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 was determined by silicone oil addition. Polymer fractionation by preparative size exclusion chromatography afforded five different microsphere batches. Average molecular weight determined the existence, width, and displacement of the "stability window" inside the phase diagrams, and also microsphere characteristics such as core loading and amount released over 6 hr. Further, the gyration and hydrodynamic radii were measured by light scattering. It is concluded that the polymer-solvent affinity is largely modified by the variation of average molecular weights owing to different levels of solubility. The lower the average molecular weight is, the better methylene chloride serves as a solvent for the coating material. However, a paradoxical effect due to an increase in free carboxyl and hydroxyl groups is noticed for polymers of 18,130 and 31,030 SEC (size exclusion chromatography) Mw. For microencapsulation, polymers having an intermediate molecular weight (47,250) were the most appropriate in terms of core loading and release purposes. PMID- 2235893 TI - Physicochemical factors associated with binding and retention of compounds in ocular melanin of rats: correlations using data from whole-body autoradiography and molecular modeling for multiple linear regression analyses. AB - The relationship between the physicochemical characteristics of 27 new drug candidates and their distribution into the melanin-containing structure of the rat eye, the uveal tract, was examined. Tissue distribution data were obtained from whole-body autoradiograms of pigmented Long-Evans rats sacrificed at 5 min and 96 hr after dosing. The physicochemical parameters considered include molecular weight, pKa, degree of ionization, octanol/water partition coefficient (log Po/w), drug-melanin binding energy, and acid/base status of the functional groups within the molecule. Multiple linear regression analysis was used to describe the best model correlating physicochemical and/or biological characteristics of these compounds to their initial distribution at 5 min and to the retention of residual radioactivity in ocular melanin at 96 hr post injection. The early distribution was a function primarily of acid/base status, pKa, binding energy, and log P(o/w), whereas uveal tract retention in rats was a function of volume of distribution (V1), log P(o/w), pKa, and binding energy. Further, there was a relationship between the initial distribution of a compound into the uveal tract and its retention 96 hr later. More specifically, the structures most likely to be distributed and ultimately retained at high concentrations were those containing strongly basic functionalities, such as piperidine or piperazine moieties and other amines. Further, the more lipophilic and, hence, widely distributed the basic compound, the greater the likelihood that it interacts with ocular melanin. In summary, the use of multiple linear regression analysis was useful in distinguishing which physicochemical characteristics of a compound or group of compounds contributed to melanin binding in pigmented rats in vivo. PMID- 2235894 TI - Melting point, boiling point, and symmetry. AB - The relationship between the melting point of a compound and its chemical structure remains poorly understood. The melting point of a compound can be related to certain of its other physical chemical properties. The boiling point of a compound can be determined from additive constitutive properties, but the melting point can be estimated only with the aid of nonadditive constitutive parameters. The melting point of some non-hydrogen-bonding, rigid compounds can be estimated by the equation MP = 0.772 * BP + 110.8 * SIGMAL + 11.56 * ORTHO + 31.9 * EXPAN - 240.7 where MP is the melting point of the compound in Kelvin, BP is the boiling point, SIGMAL is the logarithm of the symmetry number, EXPAN is the cube of the eccentricity of the compound, and ORTHO indicates the number of groups that are ortho to another group. PMID- 2235895 TI - Enhanced delivery of zidovudine through rat and human skin via ester prodrugs. AB - In an attempt to improve the skin delivery characteristics of Zidovudine (AZT, azidothymidine), five aliphatic esters (acetate, butyrate, hexanoate, octanoate, and decanoate) of AZT were synthesized and assessed as prodrugs of AZT. While the water solubility of the esters is lower than that of AZT, the solubilities in isopropylmyristate (IPM) and the partition coefficients (n-octanol:buffer) are higher. Susceptibility to enzymatic hydrolysis in the rat skin homogenate increases as the acyl chain of the ester is lengthened. Among the esters, acetate (C2-AZT) and hexanoate (C6-AZT) showed 2.4- and 4.8-fold enhanced permeation in human skin from an apolar vehicle (IPM) relative to application of AZT itself, respectively. PMID- 2235896 TI - Comparison of single-dose and steady-state nadolol plasma concentrations. AB - The pharmacokinetics of nadolol have been previously reported to be linear between single and steady-state dosing. Data from a study in our laboratory suggested greater than expected beta-blockade with nadolol at steady state. Because the early potency studies were single-dose studies, we hypothesized there was a nonlinearity in nadolol pharmacokinetics which produced higher than expected plasma concentrations at steady state. Six normal volunteers from the previous study (steady state) volunteered to participate in the single-dose study. Plasma concentrations were determined for 24 hr following a single dose of nadolol, 80 mg. A simple, inexpensive, and accurate method for determination of nadolol in plasma or serum by HPLC with fluorometric detection is described. The AUC0-tau at steady state was greater than the AUC0-infinity following a single dose in five of the six subjects. The mean ratio of AUCss/AUCsd was 2.54. This value would be unity in the presence of linear pharmacokinetics. We conclude that the principle of superposition is not applicable for nadolol. PMID- 2235897 TI - Solubilization of liposomes by weak electrolyte drugs. I. Propranolol. AB - The solubilization of dimyristoylphosphatidylcholine (DMPC) liposomes by a weak electrolyte drug, propranolol (PPL) hydrochloride, has been studied as a function of pH, [PPL], [DMPC], and temperature. The solubilization of liposomes at 40 degrees C by 0.2 mM PPL occurred at different rates from 2.9 to 14.4 mM DMPC but converged at complete solubilization after 13 hr at pH 12.0. At the same [PPL], solubilization was complete after 18 days at pH 11.0, but incomplete solubilization occurred at pH 10.0 and not at all at lower pH's. In 14.4 mM DMPC liposomes, solubilization was gradual and proportional to the [PPL] from 0.001 to 0.10 mM up to 95 hr, then rapid thereafter. The [PPL] at which the solubilization efficiency began to increase rapidly was determined to be 0.078 mM. The rate of solubilization was also influenced by the fluidity of the bilayers, a sevenfold increase in the time for complete solubilization being observed upon cooling from 40 to 20 degrees C. Surface tension (st) data confirmed a low critical micelle concentration (CMC) and continued decrease in the st above the CMC. It is concluded that the critical ratio of PPL to DMPC for solubilization occurs in localized regions of the bilayers, with total solubilization at different rates depending on the [PPL] and the physical properties of the liposomes. The processes may be used advantageously to prepare small vesicles or to extract lipids or proteins, more efficiently than detergents, from biological membranes. PMID- 2235898 TI - Particle size and content uniformity. AB - The requirements of the USP Content Uniformity test are translated into physical and mathematical parameters. Assuming spherical particle sizes with a log normal distribution, the mean particle size and particle size distribution required to insure a high probability of passing the content uniformity test are calculated. On the basis of these calculations it is shown that satisfactory tablets of low doses cannot be manufactured from a drug that does not meet certain particle size distribution specifications. It is recommended that particle size specifications for low dose drugs include a requirement for a limit to size distribution. PMID- 2235899 TI - Influence of solute degradation on the accumulation of solutes migrating into solution from polymeric parenteral containers. AB - Solute stability in solution, in addition to solute-polymer interaction properties and the total solute available pool, impacts the interaction between a polymeric container and a parenteral product, specifically in terms of the migration of trace polymer components into the contained solution. A specific solute/polymer system has been studied with respect to properties impacting the magnitude and rate of solute migration from the polymer into solution. The solute, an alkyl ester, originates in a polyolefin composite packaging material. Solute degradation kinetics were studied as a function of solution temperature and pH. Solute-polymer interaction properties including the equilibrium binding constant and diffusion coefficient were obtained. An accumulation rate model is developed for the determination of the solution phase concentration of the liberated solute as a function of storage time and conditions. Coupling the model with the properties of the polymer-solute system studied provides a tool that accurately predicts solute accumulation behavior in a representative parenteral product configuration. PMID- 2235900 TI - The significance of trisomy 7 mosaicism in chorionic villus cultures. AB - Two cases of mosaic trisomy 7 confined to the cultured cells and not found in direct preparation were detected from 200 consecutive first-trimester chorionic villus samples (CVS) analysed. The mosaicism was similar in the two cases, but the pregnancy outcome was different. In both cases, the direct metaphases from the CVS were 46,XY. Culture metaphases were mos46,XY/47,XY, +7; the trisomy 7 was seen in 34 per cent of cells from case 1 and 53 per cent from case 2. A sonogram at 15 1/2 weeks revealed fetal death in utero in case 1, and the patient declined amniocentesis. The fetal tissue failed to grow in culture, but the placental cultured cells were 47,XY, +7 in 28 (100 per cent) cells analysed. In the second case, all the amniotic fluid cells were 46,XY and the pregnancy resulted in a normal male with a 46,XY karyotype in the cord blood and foreskin fibroblast cultures. The term placenta was mosaic with 13/163 (8 per cent) trisomy 7 cells. Extensive cytogenetic studies on the placenta for the first time confirmed trisomy 7 mosaicism confined to the villus cultures. PMID- 2235901 TI - The risks of early cordocentesis (12-21 weeks): analysis of 500 procedures. AB - Five hundred cordocenteses were performed between 12 and 21 weeks. The indications were thalassaemia (386), rapid karyotyping (97), feto-maternal allo immunization (10), rubella (6), and toxoplasmosis (1). One hundred and ten pregnancies underwent termination on the basis of the result, while 20 of the 370 pregnancies intended to continue were lost to follow-up. Amongst these were 16 fetal losses (4.3 per cent) and 22 premature deliveries (5.9 per cent); no other complications were reported. Four adverse prognostic factors were identified: (a) cord bleeding; (b) fetal bradycardia; (c) prolonged procedure time; and (d) anterior insertion of the placenta. There was no 'obvious' difference in fetal loss rate with advancing gestation until 19-21 weeks, when the risk of fetal loss decreased to 2.5 per cent. PMID- 2235902 TI - Holoprosencephaly: prenatal diagnosis by sonography and magnetic resonance imaging. AB - Magnetic resonance (MR) imaging was performed on two women at the 33rd and 34th pregnancy week, respectively, after ultrasonographic detection of a brain malformation. Fetal neuromuscular blockade was induced by pancuronium bromide injected into the umbilical vein under continuous ultrasound (US) guidance. MR images supported the echotomographic diagnosis of holoprosencephaly, improving the image quality and offering additional information in such cases of difficult differential fetal diagnosis. Holoprosencephaly was finally confirmed by neonatal US and autopsy (case 1), US, CT and MR (case 2). PMID- 2235903 TI - Limb reduction and chorion villus sampling. AB - Upper limb reduction was diagnosed by ultrasound scan at 17 weeks after chorion villus sampling at 9 weeks' gestation. Pregnancy was terminated and necropsy confirmed limb reduction in an otherwise normal fetus. The relationship of limb reduction to amniotic band syndrome is discussed. PMID- 2235904 TI - Ultrasound diagnostic features of twin reversed arterial perfusion sequence. AB - Two cases of twin reversed arterial perfusion (TRAP) sequence with relevant ultrasound features that would help an accurate diagnosis are described. Available management options are proposed and discussed. PMID- 2235905 TI - Risks of transabdominal chorionic villus sampling before the 12th week of amenorrhea. AB - The authors report on a series of 210 chorion villus sampling diagnoses made with a needle by the transabdominal route. The rate of fetal loss was 4.2 per cent. Placental localization was important: fetal losses were 8 per cent when the placenta was strictly posterior (transamniotic route), whereas it was only 1.6 per cent when it was not posterior. Moreover, all fetal losses occurred (apart from one at 12.5 weeks of amenorrhea) before the 12th week of amenorrhea. The authors suggest that choriocentesis by the transabdominal route should not be performed before the 12th week of amenorrhea, and that the amniotic membrane should not be disturbed before the 13th week of amenorrhea. PMID- 2235906 TI - Mosaic isochromosome 20q found on amniocentesis with normal outcome. AB - A case of mosaic isochromosome 20q found on amniocentesis is described. A normal male infant was subsequently born. PMID- 2235907 TI - Successful intrauterine therapy of a large fetal ovarian cyst. AB - Fetal ovarian cysts can be managed in different ways, depending upon their size and clinical course: conservatively, by open surgery or by postnatal transabdominal puncture. However, in cases of large cysts detected antenatally and affecting the ongoing pregnancy, in utero transabdominal puncture can be undertaken, without increase of risk. A case of such a puncture at 30 weeks gestation is reported. PMID- 2235908 TI - Hematoma of the umbilical cord secondary to cordocentesis for intrauterine fetal transfusion. PMID- 2235909 TI - In utero resolution of a fetal cystic hygroma in a male with a 46,XY karyotype and normal development at one year. PMID- 2235910 TI - Supernumerary ribs and vertebrae in trisomy 9 syndrome. PMID- 2235911 TI - High-performance liquid chromatography of proteins on deformed nonporous agarose beads. Affinity chromatography of dehydrogenases based on cibacron blue derivatized agarose. AB - Nonporous agarose beads, prepared by shrinkage and cross-linking in organic solvents, were derivatized with Cibacron Blue F3G-A. A compressed bed of these beads was used for purification of dehydrogenases (glucose-6-phosphate dehydrogenase, lactate dehydrogenase and alcohol dehydrogenase). The chromatographic conditions for the purification of glucose-6-phosphate dehydrogenase were optimized by varying the pH of the buffer; the concentrations of eluting agents, i.e. NADP (specific elution) and sodium chloride (nonspecific elution); flow rate; residence time of the protein on the column bed; and protein load. Specific elution with NADP (2 mM in 0.025 M Tris-HCl, pH 8.0) gave the highest recovery (140%) and highest purification factor (200-fold) of the enzyme. The ability of the compressed bed of nonporous agarose beads to tolerate high flow rates was essential, since the recovery of the enzyme activity increased with an increase in flow rate. PMID- 2235912 TI - High-yield purification of glucokinase from rat liver. AB - A rapid and reliable method for the purification of rat liver glucokinase was developed. The procedure consists of DEAE-cellulose ion-exchange chromatography, Phenyl-Sepharose hydrophobic interaction chromatography, DEAE-Affi Gel Blue dye ligand chromatography, and duplicate steps of glucosamine-Sepharose affinity chromatography. Glucokinase was purified to a specific activity of 290 units/mg protein in a yield of 55% in 6 days. The final enzyme preparations were completely homogeneous in most experiments as assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The estimated molecular weight (51,000) and sigmoidal saturation function for glucose of purified glucokinase were in good agreement with published data. PMID- 2235913 TI - Biosynthetic preparation of [riboflavin-2-14C]flavin adenine dinucleotide using Clostridium kluyveri. AB - The biosynthetic preparation of [riboflavin-2-(14)C]flavin adenine dinucleotide from extracellular [2-(14)C]riboflavin by a growing culture of Clostridium kluyveri, first reported by Decker and coworkers, has been implemented using new media and more convenient isolation procedures. PMID- 2235914 TI - Expression of human placenta alkaline phosphatase in placenta during pregnancy. AB - To clarify the expression of PLAP during the course of pregnancy, the amount of PLAP mRNA and its activity in normal placental villi were measured. Both PLAP and its mRNA were found in placentae of as early as 7 weeks of gestation, and they continued to increase throughout pregnancy. But they showed different patterns of increase. The amount of PLAP mRNA began to increase dramatically around 13th week and probably continued to increase gradually until term. PLAP activity per gram of villi showed a gradual increase from around 13th week and a marked increase was observed after about 20th week. PLAP levels in sera from pregnant women were also measured, and they showed a pattern of increase imilar to that of PLAP activity per gram of villi. The continuous increase in the expression of PLAP throughout pregnancy suggests that PLAP may play a role in feto-maternal metabolism and placental differentiation. PMID- 2235916 TI - Human trophoblast-endometrial interactions in an in vitro suspension culture system. AB - We developed an in vitro suspension co-culture system to examine the interaction of 1st, 2nd and 3rd trimester purified cytotrophoblasts with human endometrium. Endometrium explants were added to cytotrophoblast cell suspensions and placed on an angled gyrating platform in a 37 degrees C incubator. When endometrium was cultured alone it was able to remain viable for up to 3 days. When trophoblasts were cultured alone, they formed small and large aggregates, and occasionally spherical shells with hollow centers. When trophoblasts and endometrium were cultured together, the trophoblasts adhered to the exposed stromal surfaces of the tissue fragments. The surface epithelium was not receptive to trophoblast attachment except in one experiment when day 19 endometrium was used for the co incubation, suggesting that surface attachment is usually restricted. A common finding was the presence of an acellular zone in the endometrium only adjacent to the attached trophoblasts. We speculate that this zone may be caused by proteolysis and resynthesis of ECM proteins by the trophoblasts. Based on our results, this in vitro suspension should prove useful for examining those factors which: (1) induce endometrial permissiveness, (2) promote paracrine effects on the endometrium, and (3) facilitate human trophoblast invasion. PMID- 2235918 TI - Community cholesterol screening: medical follow-up in subjects identified with high plasma cholesterol levels. AB - Population screening or plasma cholesterol is an effective method of detecting hypercholesterolemia; however, follow-up and treatment are essential components of such a program. After a city-wide screening in 1987 of more than 19,872 persons, using a mailed survey with a response rate of 48%, we evaluated subsequent actions of 3,078 individuals with high plasma cholesterol levels. Slightly more than half the population was aware of high blood cholesterol levels prior to the time of screening and apparently used the program for follow-up. Overall, after the screening, 65% consulted a physician within 5 months of screening and blood cholesterol levels were remeasured in 80% of the sample. Procrastination and expense were cited as the primary reasons for failing to consult a physician. If screening is to be effectively utilized as a means of reducing the prevalence of high plasma cholesterol levels, diligent follow-up must be made of all individuals identified to be at increased risk on the basis of their initial values. PMID- 2235915 TI - Differential control of placental lactogen release and progesterone production by ovine placental tissue in vitro. AB - The hypothesis that placental secretion of progesterone (P4) and ovine placental lactogen (oPL) are controlled through different mechanisms was tested. Placental tissue was obtained at days 133-138 of pregnancy, and explant incubations were established using 200 mg tissue per flask in 5 ml O2-saturated DMEM containing 24 mM HEPES and lacking phenol red (pH 7.4). Following a 30-min preincubation, and a 15-min control period, test substances were added and incubations continued, with periodic gassing, for 4 h at 37 degrees C in a shaking water bath. Dopamine (DA), norepinephrine (NE) and epinephrine significantly stimulated P4 production (P less than 0.05). The enhancement of placental P4 production was mimicked by the addition of 8-bromo-cyclic adenosine monophosphate and forskolin (P less than 0.05). The response to catecholamines was abolished by the addition of propranolol (P less than 0.05) but not by phentolamine (P greater than 0.05). Inclusion of a membrane-permeant substrate for P4 synthesis, 25 hydroxycholesterol, increased basal (P less than 0.05) but did not enhance agonist-induced P4 production (P greater than 0.05). High performance liquid chromatographic analysis of placental tissue demonstrated the presence of DA (80.8 +/- 7.07 pg/mg) and NE (48.8 +/- 5.77 pg/mg), as well as catecholamine metabolites. Addition of 1,2-dioctanoyl-sn-glycerol (DAG) or phorbol 12-myristate 13-acetate (PMA) enhanced oPL secretion (P less than 0.05) without affecting P4 production. The response to DAG and PMA, representing the release of considerably more oPL than can be detected by extracting the tissue, was not influenced by treatment with cycloheximide (P greater than 0.05) indicating that secretion of preformed oPL is regulated by the protein kinase C pathway. These results support the hypothesis that the secretion of oPL and the production of P4 are controlled by different mechanisms. PMID- 2235917 TI - Routine pathological examination of placentae from abnormal pregnancies. PMID- 2235919 TI - Adherence to colorectal cancer screening in an HMO population. AB - This study aimed to determine factors that influence fecal occult blood test performance in colorectal cancer screening. A random sample was selected of men and women ages 50 to 74 years of age who had been mailed a fecal occult blood testing kit in a screening program in fall 1986. One year after initial test mailing, sample group members (n = 504) were surveyed by telephone. Four months later, the survey sample received a second fecal occult blood test mailing. Multivariable analysis for subjects with validated past fecal occult blood test status (n = 322) revealed the past testing was positively associated with physician encouragement of screening, age, the belief that cancer is curable, perceived test efficacy, and strong intention to do testing. It also was discovered that persons who felt that they had little control over their health were more likely to have done past testing. Preliminary analysis of prospective adherence showed that the strongest statistically significant independent predictor was past test performance. Prospective adherence among past nontesters (n = 121) was associated with expressed commitment to do fecal occult blood testing and reported presence of colorectal cancer risk factors. Analysis of adherence among past testers (n = 201) revealed that belief in colorectal cancer curability and age were significant predictors. The findings reported here indicate that factors influencing adherence among past nontesters differ from those for past testers. Overall, these results suggest that to increase participation in colorectal cancer screening, physicians and other health professionals should (a) deliver educational messages that increase awareness of risk factors for colorectal cancer and curability of the disease, and (b) elicit from potential screenees a commitment to engage in recommended preventive behaviors. It may also be well to consider "tailoring" messages for past nontesters and past testers, respectively, by emphasizing colorectal cancer risk factors and highlighting curability. PMID- 2235920 TI - Prevalence of lifestyle risk factors in a family practice. AB - The prevalence of eight adverse lifestyle risk factors which are linked to increased morbidity and mortality was determined. Smoking, excess alcohol use, obesity, lack of exercise, lack of seatbelt use, use of hazardous transportation vehicles, and inadequate rest were studied. A random sample of 147 patients from a private family practice were selected in a cross-sectional survey. Data were collected by mailed questionnaire. The most prevalent adverse habits were lack of seatbelt use (71%) and sedentary lifestyle (44%). Patients with multiple adverse health habits had poorer self-reported physical as well as emotional well-being. Using a factor analysis of the correlations among eight habits, no significant clustering of habits emerged as indicators of high risk. Thus, no abbreviated list of adverse lifestyle risk factors for clinical use was found that could replace a complete review of risk factors. PMID- 2235921 TI - Psychosocial predictors of physical activity in adolescents. AB - Regular physical activity consistently demonstrates an inverse relationship with coronary heart disease and has positive effects on quality of life and other psychological variables. Despite the benefits of exercise, many youth and adults maintain a sedentary lifestyle. Interventions are needed, particularly with youth, to increase levels of physical activity. A better understanding of the psychosocial predictors of physical activity will aid in structuring these interventions. Longitudinal data from a cohort of 743 10th-grade students from the control condition of the Stanford Adolescent Heart Health Program were analyzed. Regression analysis indicated that psychosocial variables were significantly related to physical activity after controlling for baseline levels of physical activity and BMI. Associations with physical activity were found for intention to exercise, self-efficacy, stress, and direct social influence. The designers of future interventions should consider including program components that target these variables. PMID- 2235922 TI - Trends in smoking by age and sex, United States, 1974-1987: the implications for disease impact. AB - Using data from the 1974-1987 National Health Interview Surveys, we report trends in current smoking prevalence and quit ratios (the proportion of those who have ever smoked who no longer smoke) for men and women in the age groups 20-24, 25 44, 45-64, and 65 years and older. Current smoking prevalence decreased linearly for men in all age subgroups except 65 and older and for women ages 25-44 and 45 64 years only. The quit ratios increased linearly within each age/sex subgroup except for men and women ages 20-24 years. Overall, there were about 1.4 million fewer male smokers and over 1 million more female smokers in 1987 than there were in 1974. Between 1974 and 1987, the population ages 25-44 years increased by approximately 47%, and the population 65 years and older increased by approximately 34%. As a result, between 1974 and 1987, the actual number of smokers increased among men ages 25-44 years (8% increase), women ages 25-44 years (15% increase), and women ages 65 years and older (50% increase). These data suggest that even with favorable recent changes in the overall smoking prevalence of the U.S. population, the disease impact of smoking will increase for decades, especially among women. This scenario will be mitigated if increased attention is given to cessation among women in general and to the post-World War II generation of both male and female smokers. PMID- 2235923 TI - The knowledge and use of screening tests for colorectal and prostate cancer: data from the 1987 National Health Interview Survey. AB - Data based on the 1987 National Health Interview Survey are presented depicting factors associated with the knowledge and use of three tests for the early detection of colorectal and prostate cancer: digital rectal examination, fecal occult blood tests, and flexible sigmoidoscopy. The percentage of the at risk adult population who have ever heard of or had these tests is reported. The association of demographic, personal resource, and health system factors with knowledge of these tests is explored using multivariate logistic regression. Health system factors are most consistently associated with use of the tests and with knowledge. Family income, family size, education, knowledge of cancer early warning signs, and measures of encounters with the health care system are associated both with knowledge of and, independent of knowledge, with use of the tests. Residency in the non-South, being white or female, and having an optimistic attitude about cancer prevention are all factors associated with greater knowledge of the tests, but not greater use among those aware of the tests. Membership in a health maintenance organization is more strongly associated with knowledge and use of fecal occult blood tests than the other tests. No association was found between current smoking status and knowledge of or use of any of the tests. PMID- 2235924 TI - [Fibrinolytic properties of protease complex isolated from the culture fluid of Nocardia minima]. AB - The protease complex isolated form the Nocardia minima culture liquid was studied in vitro. The preparation had two different activities (fibrinolytic and activating), i.e. it was able to convert plasminogen into plasmin. At a concentration of 250 micrograms/ml and above the preparation lysed experimental thrombi. The fibrinolytic activity of the preparation was completely inhibited with normal human plasma. PMID- 2235925 TI - [Characteristics of hydrolase biosynthesis in Bacillus mesentericus grown on various media]. AB - The dynamics of the consumption of major carbon and nitrogen sources and the biosynthesis of hydrolytic enzymes were studied in Bacillus mesentericus grown on semisynthetic media. Conditions were chosen that provide the obtaining of the culture liquid with predominantly proteolytic or amylolytic activity. The replacement of maltose with native starch resulted in more intensive accumulation of the biomass and hydrolytic enzymes, and in more rapid (by 3-5 hr) transformation from the logarithmic to the stationary growth phase. PMID- 2235926 TI - [Comparative characteristics of the metabolism of E. coli cells with various activity of penicillin acylase]. AB - A correlation between the synthesis and secretion of penicillin acylase (PA; EC 3.5.1.11) and the membrane phospholipid composition was observed in three E. coli strains. In cells with overproduction of PA, the phospholipid/protein ratio decreases, while the cardiolipin/phosphatidylglycerol ratio increases. The differences in the functioning of the electron transport system were revealed in cells with different levels of PA synthesis and secretion. The O2 consumption rate was 3 times lower in the cells with overproduction of PA than in those of less productive strains. On the contrary, membrane particles isolated from the cells of PA producers had no significant differences in the O2-reduction rate. The sensitivity of the strains to the inhibitor of terminal oxidases, sodium cyanide, and to the uncoupler of redox phosphorylation, chlorocarbonyl phenylhydrazone, was different. Thus the E. coli cells with PA overproduction are characterized by significant changes in energetics and constructive metabolism. The interrelations between PA overproduction, phospholipid metabolism and the respiratory chain activity are discussed. PMID- 2235927 TI - [A new pathway for the central nervous regulation of carbohydrate homeostasis]. PMID- 2235928 TI - [The functional role of membrane lipids in the mechanisms for realizing the effect of insulin]. PMID- 2235929 TI - [Sex steroid metabolism in the hypothalamus and its role in the neuroendocrine regulation of reproduction]. PMID- 2235930 TI - [The molecular genetic aspects of insulin-dependent diabetes mellitus]. PMID- 2235931 TI - [The molecular polymorphism of the growth hormone and prolactin and its clinical significance]. PMID- 2235932 TI - [The hormonal regulation of protein synthesis in liver cell cultures]. PMID- 2235933 TI - [The problems of clinical diabetology]. PMID- 2235934 TI - [The pathogenetic characteristics of diabetic nephropathy and its early diagnosis]. PMID- 2235935 TI - [Insulin and its place in the therapy of diabetes mellitus types 1 and 2]. PMID- 2235937 TI - [The hormonal-metabolic correlations in the generalized lipodystrophy syndrome]. PMID- 2235936 TI - [The role of multiple insulin injections and self-monitoring of the disease in diabetes mellitus compensation in children]. PMID- 2235938 TI - [The main trends in modern immunoendocrinology]. PMID- 2235939 TI - [Disputable aspects of the definition, diagnosis and classification of respiratory insufficiency]. PMID- 2235940 TI - [Concerning the article by T.N. Bodrova and F.F. Tetenev "Pathophysiological classification of external respiratory insufficiency"]. PMID- 2235941 TI - [Improving the diagnosis and treatment of pulmonary tuberculosis among the inmates of reformatory institutions of the Ministry of Home Affairs]. AB - According to the data given by the authors, the tuberculosis morbidity rate in the populations under surveillance of the Ministry of Home Affairs was over that in the general population. High morbidity of such persons is often contributed to their antisocial way of life, and alcohol and drug addiction. Full coverage of these groups by means of X-ray screening, when they are held prisoners during the investigation period, makes it possible to detect all cases with active tuberculosis, to prevent the admission of undetected patients to the reformatory schools and thereby to stop the transmission of tuberculous infection. The observations should be conducted twice a year since these imprisoned groups may be recognized as being at high risk for tuberculosis. The clinical pattern of pulmonary tuberculosis is unfavorable in the convicted persons. Appropriate three stage chemotherapy with the use of surgical interventions, if indicated permits one to achieve in the reformatory institutions of the Ministry of Home Affairs a high efficacy of treatment of ++newly-diagnosed pulmonary tuberculosis patients, which concurrently significantly decreases their epidemic danger for the general population when they are let free. PMID- 2235942 TI - [Intravitally undetected tuberculosis and non-registered foci od tuberculous infection]. AB - Active pulmonary tuberculosis was revealed in 1.55% of the cases registered in 11042 postmortem certificates representing forensic medical examination material accumulated at the archives for a period of 4 years. 66.35% of the cases had not been registered in a dispensary. Pulmonary tuberculosis was stated as a cause of death in 72.7% and as a concurrent condition in 27.3%. The basic activities of the antituberculosis service is to detect tuberculous infection and to rapidly eradicate its transmission. In addition, a close association and coordinated activities of forensic medical experts, phthisiologists and sanitary-and epidemiologists will ensure an improvement of the epidemiological situation. PMID- 2235943 TI - [Work capacity of patients with tuberculosis of a solitary kidney]. AB - The material for this report is based on the examination data produced from 105 patients with a single kidney who were operated on for contralateral kidney tuberculosis. The conducted clinical trial confirms the approach that the correct solution of the problems in medical labor examination depends on the nature of a pathologic process in the single kidney, clinical course of the disease and period of a pathologic process, degree of a chronic renal failure, arterial hypertension and severity of the pain syndrome. The role of social factors and the rehabilitation aspects of this type of the patients are considered. PMID- 2235944 TI - [Transbronchial biopsy of the lung and bronchoalveolar lavage in the diagnosis of sarcoidosis]. AB - The outcomes of a complex study of sarcoidosis and other interstitial pulmonary diseases in 1325 patients are presented. An important role of intrapulmonary biopsy and bronchoalveolar lavage methods in defining the diagnosis and the process activity, especially when they are used in combination, is demonstrated. Complications in the form of bleedings and pneumothorax were registered in a limited number of the patients, mainly as a result of rigid bronchoscope procedures. Differential and diagnostic signs of sarcoidosis and some other disseminations in the lung, obtained by means of biopsy, bronchoalveolar lavage and clinical data studies, are given. PMID- 2235945 TI - [Variants of the course of fibrous-cavernous pulmonary tuberculosis]. AB - Taking into account the presence of the process development symptoms or their absence (including a high rate of exacerbations, ongoing dissemination process, formation of new cavities in the affected foci, severe infiltration of the lung tissue and massive bacillary excretion), process development rate and the nature of complications, the following 4 versions of fibrous-cavernous pulmonary tuberculosis were identified: rapidly developing disease; slowly developing disease; fibrous-cavernous pulmonary tuberculosis whose clinical picture was determined by different complications; and relatively stable condition. ++Clinico roentgenological+ features of each version of the disease are described. Abnormalities in the ++clinico-roentgenological+ picture and laboratory findings are especially apparent in patients with rapidly developing fibrous-cavernous pulmonary tuberculosis. PMID- 2235946 TI - [Roentgenological diagnosis of acute lesions of the lungs with disorders of blood circulation and vascular permeability]. AB - To specify differential and diagnostic criteria of hemodynamic and non hemodynamic pulmonary edema, canine experimental simulation (15 trials) of different types of abnormal hemodynamic and lung capillary permeability parameters was carried out. The X-ray pictures of 71 patients with and acute diffuse lesion of the pulmonary vascular channel (including 51 with adult respiratory distress and 20 with hemodynamic pulmonary edema) was analysed. The findings substantiated the possibility of making a differential diagnosis of pulmonary edema of various genesis. Symptom complexes, typical of predominantly higher permeability of the lung capillaries and hemodynamic disturbance, were formulated. PMID- 2235947 TI - [Effectiveness of chemotherapy of patients with newly detected destructive pulmonary tuberculosis living in rural areas]. AB - The results of treating 333 new cases of destructive tuberculosis of the lungs were investigated in relation to the time of the disease detection and the chemotherapy regimens applied. When the disease was detected relatively early (not later than a month before registration of the pulmonary signs) the frequency of abacillation and cicatrization of the destructive cavities increased, the period of the main chemotherapy course decreased (including in- and outpatient stages) and the treatment expenditures appeared to be lower. The best results were observed with early use of the chemotherapy regimens including rifampicin, isoniazid, ethambutol and/or streptomycin at the first stage of the treatment especially when the disease was detected not later than a month before registration of the pulmonary signs. PMID- 2235948 TI - [Effect of acute respiratory viral infection on the indicators of immunity in patients with pulmonary tuberculosis]. AB - To study the impact of acute respiratory viral infection (ARVI) on the course of pulmonary tuberculosis, 150 cases with this condition were under observation. These patients were divided into 2 groups: 88 subjects who had ARVI and 62 persons who did not have it, being in hospital. In the both groups those suffering from infiltrative and focal pulmonary tuberculosis were predominant. ARVI is conducive to the aggravation of a specific process in the lungs, which was registered in 27.3% of the cases who had had ARVI, and impede the reactions of cellular immunity to restore, which can be observed during chemotherapy. Among those who had ARVI, 68.4% of the patients demonstrated a decrease in T-cells and blast transformation with PHA. A significant drop in the number of T-lymphocytes and their functional activity, as a consequence of ARVI, promotes the deterioration of the above specific process. ARVI affects the efficacy of the in patient treatment and decreases the proportion of patients with cavity closure. PMID- 2235949 TI - [Clinico-functional characteristics of the external respiratory system and central hemodynamics in patients with pulmonary tuberculosis]. AB - Lung ventilation and central hemodynamics in the course of treatment of 43 patients with pulmonary tuberculosis were studied. Registered ventilation and hemodynamic disturbances disappeared with an effectively conducted chemotherapy. PMID- 2235951 TI - [Tisamide in the complex treatment of tuberculosis]. AB - The outcomes of tisamid treatment of newly diagnosed patients with bacillary pulmonary tuberculosis were analysed. To estimate the efficacy of tisamid and its administration indications, chemotherapy of the patients was performed with the use of two therapeutic regimens. Isoniazid, rifampicin and streptomycin (or ethambutol) were given to 73 patients, while other 72 ones were treated with the same drugs plus tisamid. The patients in each group were subdivided into slow, rapid and homozygotic (the most rapid) acetylators. Tisamid, when prescribed to newly-discovered patients with destructive tuberculosis, accelerates recovery, by excluding the risk of a hepatotoxic action. Tisamid in a combined treatment with isoniazid, rifampicin and streptomycin is mostly recommended for patients with a rapid acetylation phenotype, i.e. the cases for whom a short-term chemotherapy is possible. PMID- 2235952 TI - [The role of genetically determined haptoglobin phenotypes in patients with destructive pulmonary tuberculosis]. AB - Haptoglobin (Hp) was phenotyped in 567 apparently healthy individuals and 223 patients with destructive pulmonary tuberculosis, including 163 as newly-detected and 60 as recurrent cases. Three phenotypes of haptoglobin were identified, i.e. two homozygotic (Hp 1:1 and Hp 2:2) and one heterozygotic (Hp 2:1). It was revealed that among the pulmonary tuberculosis patients, both newly detected and recurrent cases, the number of Hp 2:2 carriers significantly increased, as compared to healthy individuals, while that of Ph 2:1 carriers decreased. A certain relation between the course of destructive pulmonary tuberculosis and genetically determined types of Hp was found. Sputum conversion and cavity closure in Hp 2:2 and Hp 1:1 phenotype carriers, as compared to Hp 2:1 ones, occurred more infrequently and in later periods. It is felt that the presence of the 2:2 phenotype is an adverse hereditary factor in relation to tuberculosis. PMID- 2235950 TI - [Prognostic value of functional methods of the study of respiration and blood circulation in surgery of tuberculous spondylitis]. AB - Prognostic value of the basic indices of the external respiration function and central hemodynamics in view of predicting the nature of an early postoperative period in tuberculous spondylitis patients is demonstrated. Such indices, as vital capacity, ventilation and hemodynamic supply indices, and mean pressure in the pulmonary artery have the greatest prognostic value. One-dimensional analysis of variance of the functional examination data obtained from 209 patients with tuberculous spondylitis was used in this study. PMID- 2235953 TI - [Correction of protease-protease inhibitor imbalance by intrapulmonary administration of contrical in the treatment of patients with chronic nonspecific lung diseases]. AB - The ratio of proteinases and their inhibitors in bronchoalveolar washings was studied in 38 patients with chronic nonspecific diseases of the lungs. A decrease in the inhibitor potential was detected. Contrical, an inhibitor of proteolytic enzymes, was used in the treatment of the patients. A new procedure for trans thoracic++ intrapulmonary administration of contrical with an ISI-1 needle jet injector was shown to be efficient. It provided delivery of the drug in optimal daily doses immediately into the inflammation focus. PMID- 2235954 TI - [Natural antibodies, homoreactants and R-proteins in patients with tuberculosis after effective and insufficiently effective chemotherapy]. AB - The cellular receptor decay products R proteins and resultant product immunoglobulin complexes, homoreactants showing the properties of natural antibodies and natural anti-sheep erythrocyte antibodies were analysed in their dynamics in 116 patients with infiltrative pulmonary tuberculosis. It was found that small homoreactant levels and relatively low titers of R proteins and natural sheep anti-erythrocyte antibodies were typical of patients with a limited process and favorable course due to effective treatment, the parameters being gradually normalized in their dynamics. In patients with a disseminated destructive process running an unfavorable course, all the values were much higher before the treatment and slightly changed during an ineffective therapy. It is suggested that the findings may be useful in the clinical management of pulmonary tuberculosis to predict its course and outcomes and to evaluate the efficacy of chemotherapy. PMID- 2235955 TI - [Dynamics od reparative processes in bronchial stump after pneumonectomy in experimental animals]. AB - Repair processes in the bronchus stump after pneumonectomy in 25 rats and 25 guinea-pigs were analysed. The tests were conducted on 1, 3, 7, 14 and 30 days of the postoperative period using bronchus stump and its bottom material for semithin ++ slices and electron microscopy, respectively. At early stages, besides necrotic and necrobiotic changes in the bronchus stump, compensatory and adaptive reactions are also observed. 14 days after operation there was a restoration of epithelial lining and formation of granulation tissue around the stitches. By the 30-th day considerable degenerative and functional changes are detected in the lamina proper, including its cellular elements, as well as in the structure of collagenic, elastic and smooth muscular fibers. Basal cells, endotheliocytes and fibroblasts are the most active sources of regeneration. PMID- 2235956 TI - [Differential diagnosis of allergic pneumonia and tuberculosis]. PMID- 2235957 TI - [Chemotherapy of newly detected destructive pulmonary tuberculosis in patients with pathology of the gastrointestinal tract and liver]. PMID- 2235958 TI - [Treatment of patients with tuberculosis and alcoholism]. PMID- 2235959 TI - [Causes of long-term disability of patients with tuberculosis]. PMID- 2235960 TI - [A case of a generalized form of primary tuberculosis in a 3-year-old child]. PMID- 2235961 TI - [Immediate and late results of surgical treatment of tuberculosis in patients with diabetes mellitus]. PMID- 2235962 TI - [Rare complication of neurogenic tumor of the mediastinum]. PMID- 2235963 TI - Pancreatic cancer and androgen metabolism: high androstenedione and low testosterone serum levels. AB - Serum androstenedione and testosterone levels were measured in 39 male patients with pancreatic cancer, and compared with the values obtained from 37 male patients with chronic pancreatitis or benign obstructive jaundice, and with those from 36 male patients with other gastrointestinal malignancies. Mean androstenedione values were significantly higher in the pancreatic cancer patients when compared to both control groups, and mean testosterone levels were significantly lower. The testosterone/androstenedione ratio was calculated and was also found to be significantly lower in the patients with pancreatic cancer. There was no difference in this ratio or in the androstenedione or testosterone levels when comparing both control groups. In two patients with stage I pancreatic cancer, serum androstenedione and testosterone levels were significantly altered, and returned to normal values after successful resection. These results confirm previous findings indicating that there is significant derangement in the androgen profile of patients with pancreatic cancer. PMID- 2235964 TI - Diameter of the main pancreatic duct in chronic calcifying pancreatitis. Measurement by ultrasonography versus pancreatography. AB - The aim of this study was to compare the diameter of the main pancreatic duct measured by ultrasonography (US) and endoscopic pancreatography (ERCP) in cases of chronic pancreatitis and to evaluate the ability of US to gauge the dilation of the main duct accurately enough to do a side-to-side wirsungo-jejunostomy. Sixty-one measurements were recorded in 50 patients (47 men and 3 women; age: 43.7 +/- 10 years). In 11 cases, two measurements were made at an interval of more than one year. US always preceded ERCP. The measurements were compared in only 43 cases (71%), because evaluation by US was inaccurate in 14 cases (23%) and by ERCP in nine cases (15%). The mean value of the diameter measured by US was 4.30 +/- 3.01 mm, and by ERCP, 5.52 +/- 3.08 mm (mean +/- SD). When the diameter assessed by US (y) was greater than or equal to 3 mm, the diameter assessed by ERCP (x) was always greater than or equal to 4 mm. The value of x could be determined from y by the equation: x = y + 1.2 mm (r = 0.91, p less than 0.05) The difference between x and y was constant and did not depend on the size of the duct. It could be owing to the hyperechogenicity of the duct walls. We conclude that US is a reliable way to assess the dilation of the main pancreatic duct and might be an acceptable method of judging whether a side-to-side wirsungo jejunostomy can be performed. PMID- 2235965 TI - Metal ions induce expression of metallothionein in pancreatic exocrine and endocrine cells. AB - Northern blot hybridization established that metallothionein (MT) mRNA levels were dramatically elevated in the rat pancreas following injection of Cd or Zn salts. To determine which pancreatic cell types express the MT gene, Northern blot hybridization analysis of RNA from preparations enriched for acini, in situ hybridization, and immunocytochemistry were used. RNA from pancreatic acini of Zn treated rats contained high levels of MT mRNA. In control rats, in situ hybridization suggested very low levels of MT mRNA in both exocrine and endocrine cells in the pancreas, but these levels were dramatically increased in both these cell populations following metal injection. In contrast, levels of insulin-I mRNA in the endocrine cells were not affected by metal injection. A similar result with MT mRNA was obtained in mouse and chicken pancreas using Northern blot and in situ hybridization. Immunocytochemistry detected MT in the rat acinar cell cytoplasm following metal injection. Although inconsistent with in situ hybridization studies and immunocytochemical analysis of exocrine cells, immunocytochemistry for MT indicated a uniform staining pattern of islet cells that was unaffected by metal treatment. These results establish that metal ion induction of the MT genes in pancreas occurs in both endocrine and exocrine cells, which suggests that this protein has diverse physiologic functions in this organ. PMID- 2235966 TI - Geranyl-geranyl acetone: a novel stimulant of secretin release in the dog. AB - Geranyl-geranyl acetone (GGA), a new acyclic polyisoprenoid, anti-ulcer drug appears to exert its beneficial effect by stimulating bicarbonate secretion from the stomach and pancreas. Its efficacy in stimulating pancreatic bicarbonate is particularly striking, and this study was designed to examine the mechanism for this action. Since it is structurally similar to the side chain of the prostaglandin molecule, its ability to stimulate bicarbonate secretion could be a direct one. On the other hand, the magnitude of pancreatic bicarbonate response (about 50% of maximal response to secretin) suggests it might act by releasing secretin. Two types of experiments were performed in dogs with pancreatic fistulas: first, secretagogue interactions were examined by studying the effect of intraduodenal GGA (8 mg/kg) or its carrier (control) on the dose-response curves to exogenous secretin and cholecystokinin octapeptide (CCK-8); second, the effect of graded doses of intraduodenal GGA on pancreatic bicarbonate and plasma secretin-like immunoreactivity (SLI) responses was tested directly. Pancreatic bicarbonate responses (micromoles per 30 min) were to secretin doses of 32, 125, and 500 ng/kg/h. Without and with GGA, responses were 74 +/- 27, 952 +/- 215, and 2,000 +/- 425 and 599 +/- 110, 1,624 +/- 472, and 2,129 +/- 398 ng/kg/h, respectively. Similarly, the bicarbonate responses to CCK-8 were augmented. Basal plasma SLI was 1.5 +/- 0.6 pM/ml. Peak plasma SLI in response to 2, 4, and 8 mg of GGA intraduodenally were 6.8 +/- 0.7, 8.9 +/- 3.1, and 19.6 +/- 2.7 pM/ml, respectively. It is concluded that GGA is a potent stimulant of pancreatic bicarbonate secretion, and this action appears to be mediated by the release of duodenal secretin. PMID- 2235967 TI - Malabsorption of vitamin B12 in pancreatic insufficiency of the adult and of the child. AB - Vitamin B12 can bind two carrier proteins in the digestive tract, haptocorrin (R binder) and intrinsic factor, but only its binding to intrinsic factor allows its absorption. A malabsorption of vitamin B12 is observed in about 30% of adult patients with exocrine pancreatic insufficiency, using the Schilling test. None of the hypotheses that have tried to explain this malabsorption are entirely satisfactory. A failure to degrade haptocorrin can prevent the binding of vitamin B12 to intrinsic factor. It has also been suggested that pancreatic secretion could modify the structure of intrinsic factor, enabling the uptake of the vitamin B12-intrinsic factor complex by the ileum. Other factors can also affect the binding of vitamin B12 to intrinsic factor, such as the gastric pH and bile. The Schilling test is abnormal in nearly all cases of cystic fibrosis. One explanation could be the gastric hyperacidity observed in this disease. Despite the frequency of abnormal Schilling tests, vitamin B12 deficiency is very rare in cases of exocrine pancreatic dysfunction, in adults as well as in children with cystic fibrosis. The assimilation of this vitamin with a tracer included in food instead of the crystalline labeled cobalamin used in the Schilling test remains to be investigated. PMID- 2235968 TI - Treatment of acute alcoholic pancreatitis in cats. AB - We created acute pancreatitis in cats by instilling ethanol (20 ml of a 40% solution) into the stomach and then perfusing activated pancreatic enzymes through the main pancreatic duct. Edematous pancreatitis developed within 24 h as the enzymes leaked out of the duct into the surrounding pancreatic parenchyma. We tested the effects of a number of agents on the amelioration of the severity of the pancreatic inflammation. Cimetidine (an H2 receptor blocker) and Benadryl (an H1 receptor blocker) given in combination decreased the incidence of pancreatic hemorrhage but not the overall degree of inflammation. Indomethacin (a cyclooxygenase inhibitor) had a similar effect. Terbutaline (a beta-agonist) given alone decreased the overall degree of inflammation, including the incidence of hemorrhage. All of the drugs given together were no more effective than terbutaline alone. The combination was effective even when given up to 12 h after the onset of pancreatitis. PMID- 2235969 TI - Demonstration of a new resonance peak by proton NMR in rat pancreas stimulated with caerulein. AB - Low-resolution proton nuclear magnetic resonance (1H NMR) analysis of the pancreas of rats stimulated with caerulein, a cholecystokinin analog, was found to differ from that of control rats either fed ad libitum or fasted for two days. The hormonal stimulation induced (a) an increase in the longitudinal relaxation time T1; (b) a 1H NMR peak situated at 1.8 +/- 0.2 ppm from the resonance peak of tissular water. This resonance peak was not observed in the pancreas of fasted rats, although it could just be detected in the pancreas of rats fed ad libitum. These features were not observed after injection of lorglumide, an antagonist of cholecystokinin, followed by caerulein stimulation. On the other hand, stimulation with secretin induced a slight increase in T1 but did not lead to the appearance of the 1.8 +/- 0.2 ppm peak. The 1.8 +/- 0.2 ppm resonance peak thus appears to be related to the hormone-stimulated state of the exocrine pancreas and might be a useful indicator of the physiological state of exocrine pancreatic tissue. From ultrastructural examination of pancreatic cells and 1H NMR studies of solutions of the major membrane phospholipids in rat plasma, we concluded that the 1.8 +/- 0.2 ppm resonance peak stemmed from an alteration in the metabolism of membrane phospholipids and/or an increase in membrane fluidity after stimulation of acinar cells by caerulein. PMID- 2235970 TI - Manganese modulates protein phosphorylation in the rat pancreas: in vitro evidence for cation selective regulation. AB - The effects of manganese (Mn2+) on phosphorylation activity in the rat pancreas were examined in an in vitro phosphorylation assay and by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of endogenous proteins. Several histones were phosphorylated in the presence of pancreatic supernatant obtained following a 10-min centrifugation at 15,000 g. The histone preference for this reaction was VII-S greater than V-S or II-S greater than III-S greater than other histones. The Mn2+ (10 mM) enhanced the phosphorylation of some histones (II-A, III-S, VI-S, and VIII-S) but inhibited the phosphorylation of other histones (II S, V-S, and VII-S). The same concentration of Mn2+ also enhanced the incorporation of 32P into cytosolic proteins in the absence of exogenous histones. This effect was not mimicked by Ca2+, Mg2+, Ba2+, or Zn2+. Analysis of endogenous proteins by SDS-PAGE revealed Mn2(+)-dependent and time-dependent phosphorylation of high (98-200-kDa), intermediate (59-,52-,35-, and 30-kDa), and low-molecular weight proteins. The Mn2+ exerted similar effects in the presence of pancreatic cytosol obtained following a 60-min centrifugation at 100,000 g. However, the 35- and 30-kDa phosphoproteins and the low-molecular weight proteins were not readily visible. In both the 15,000- and the 100,000-g preparations, there was a dose-dependent increase in the phosphorylation of the Mr 98-kDa protein (p98) at concentrations ranging from 0.03 to 1.0 mM Mn2+ but a lesser stimulatory effect at 10.0 mM Mn2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235971 TI - Effect of synthetic human cholecystokinin-33 on pancreatic blood flow in dogs. AB - We have examined the effect of synthetic human cholecystokinin (CCK-33 and CCK-8) on pancreatic blood flow and protein output in anesthetized dogs. Human CCK-33 and CCK-8 increased pancreatic blood flow and protein output in a dose-related manner. There were no significant differences in increasing pancreatic blood flow between human CCK-33 and CCK-8, and increases in blood flow were closely related to the increase of the pancreatic enzyme secretion. L-364,718 (20 nmol/kg) caused a potent inhibition of CCK-stimulated pancreatic blood flow as well as protein output. The degree of inhibition by L-364,718 was dependent on the amount of CCK infused. This study demonstrates that increasing effect on pancreatic blood flow may be one of the biological actions of CCK mediated via CCK receptor. The CCK 33, one of longer molecular forms of CCK, is an important biological stimulator of pancreatic blood flow as well as of exocrine pancreatic secretion. PMID- 2235972 TI - Atropine enhances food-stimulated CCK secretion in the rat. AB - The effect of atropine on plasma cholecystokinin (CCK) and pancreatic secretion during intraintestinal infusion of a conventional defined formula liquid diet (Ensure HN, Ross Laboratories, 1.06 kcal/ml) was studied in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice, which were returned to the duodenum at all times. Pancreatic secretion was monitored during intraduodenal infusion of 0.15 M NaCl for 2 h followed by Ensure HN, both infused at 4.62 ml/h. Rats were infused i.p. with atropine (500 micrograms/kg/h) or vehicle throughout the experiment, beginning 1 h before monitoring of basal pancreatic secretion. Basal and 15 min postprandial plasma CCK concentrations were determined by bioassay. Atropine inhibited basal pancreatic protein secretion by approximately 60%. However, protein secretion during infusion of the diet was not decreased by atropine, due to a larger incremental pancreatic protein secretory response in atropine-treated rats. Plasma CCK 15 min after beginning the diet infusion was significantly increased by atropine (8.09 +/- 1.77 pM in atropine-treated rats versus 3.14 +/- 0.64 pM in controls). The results indicate that rats compensate for loss of cholinergic input to the pancreas by increasing CCK release in response to a meal. This is hypothesized to occur by virtue of reduced feedback inhibition of CCK release due to anticholinergic reduction of basal levels of intestinal protease activity. PMID- 2235973 TI - Increased body weight as a prognostic parameter for complications in the course of acute pancreatitis. AB - To evaluate whether obesity is a negative prognostic parameter in the course of acute pancreatitis, we examined 149 patients and divided them into four weight groups. Single (methemalbumin) and multiple (Ranson's signs) prognostic parameters were found to be independent of increased body weight in all groups, although the incidence of patients with more than six Ranson's signs or a positive methemalbumin test was highest in the most obese group. There was also no direct positive correlation between increased body weight and the incidence of mortality and late complications such as pseudocysts and abscesses. However, when compared with patients of normal weight, the obese groups showed a slight increase in the incidence of early complications such as shock and renal insufficiency and a significant increase in respiratory insufficiency necessitating artificial ventilation. Thus, increased body weight was associated with increased incidence of early extrapancreatic complications. PMID- 2235974 TI - Deduced amino acid sequence of heme binding region of chicken cholesterol side chain cleavage cytochrome P450. AB - The primary structure of the carboxy terminal 296 amino acids of chicken cholesterol side chain cleavage cytochrome P450 (P450scc) was deduced from a partial cDNA clone isolated from a chicken ovarian cDNA library. The sequence contained putative steroid binding and heme binding regions. Comparison of this sequence with the corresponding sequences of three mammalian forms of P450scc shows greater than 50% homology. The heme binding region of the avian P450scc shows 76% homology with the heme binding regions of rat and human P450scc and 81% homology with that of bovine P450scc. PMID- 2235975 TI - Reorganization and merging of the EMBL and GenBank keyword indexes in a tree structure for more efficient retrieval of nucleic acid sequences. AB - EMBL and GenBank keyword indexes have no hierarchical structure. In this paper we present a method for merging and reorganizing them in a tree structure whose primary roots are the keywords 'protein', 'DNA', 'RNA', and 'unclassified'. Synonymous keywords have been grouped together and erroneous keywords have been corrected. This taxonomic organization of keywords results in a more extensive and efficient retrieval which is further aided by "synonyms declaration". The tree has been produced using the computer programs GENPOINT and CREANET. PMID- 2235976 TI - Species comparison of calmodulin sequences. AB - No amino acid substitutions can be located when the calmodulin produced in various vertebrate species (human, rat, chicken, toad) are compared. However, multiple substitutions exist in calmodulin derived from non-vertebrates. Here, we have determined the residues for which no alterations in sequence are allowed. The protein from each species exhibits a sequence identity from residue 27 to residue 53, i.e., residues spanning a small part of the Ca2+ binding loop I and the adjacent interloop region. The analogous sequence (residues 100 to 129) abutting the Ca2+ binding loop III also exhibits only a few differences. Furthermore, negatively charged side chains at residues 82-84 in the central alpha-helix are conserved. PMID- 2235977 TI - The following protein sequences were reprinted from the protein sequence database of the Protein Identification Resource (PIR). PMID- 2235978 TI - The mutagen = carcinogen controversy. PMID- 2235979 TI - In memoriam Chapman H. Binford. PMID- 2235980 TI - Reversal by antrectomy of endocrine cell hyperplasia in the gastric body in pernicious anemia: a morphometric study. AB - Multifocal gastric carcinoid tumors occasionally develop in patients with pernicious anemia, associated with hyperplasia of endocrine cells in the atrophic and metaplastic gastric body mucosa. This constellation of findings probably requires a trophic drive from hypergastrinemia associated with antral G cell hyperplasia, a consequence of achlorhydria in these patients. We report a case in which antrectomy was performed on such a patient in order to abrogate the trophic stimulus. Antrectomy was followed by resolution of hypergastrinemia and a decrease in the size of polyps endoscopically. Nine months later, the gastric remnant was resected. Using morphometric techniques, endocrine cells in the initial antrectomy specimen (which included body mucosa at the resection line) were compared with those in the subsequently removed gastric body. Antrectomy resulted in striking decreases in number (137 versus 34/mm2; P = 0.0001) and size (93 versus 56 microns2; P = 0.0001) of endocrine cells of body mucosa. The findings suggest that antrectomy may be useful in the management of endocrine cell hyperplasia, and possibly also associated carcinoid tumors, in pernicious anemia. PMID- 2235981 TI - An autopsy study of the structure of the small vessels in biopsies from the lingula and upper and lower lobes: implications for vascular assessment. AB - We examined the structure of the muscular pulmonary arteries in the three lung sites most often used for lung biopsy. In a subset of cases, we also examined tissue from the central portion of the lower lobe. In each vessel we measured the area of intima and muscle media and expressed these data as a percentage of the total tissue area; vessel size was standardized by using the length of the internal elastic lamina. We found that no one biopsy site best represented the arterial structure of the central aspect of the lower lobe. The lingula had greater numbers of arteries which met the criteria for assessment from than did the other biopsy sites. The vessel structure was similar between the lingula and peripheral aspect of the upper lobe, but the lingula had a slightly increased area of muscle media and decreased intima when compared with the superior segment of the lower lobe. This was not a function of vessel size, since the overall cumulative distribution curve of percent muscle divided by length of internal elastic lamina was also shifted between lingula and lower lobe. We conclude that, in the assessment of arterial vascular structure, any of the standardly used biopsy sites can be representative of the lung. Although there may be differences in structure between the sites in individual patients depending on concurrent disease in any of the sites, there is no consistent site effect on vessel structure. If a formal morphometric evaluation of arterial structure is required, the lingula appears to have more vessels which fit the criteria for assessment. PMID- 2235982 TI - Comparison of fine-needle aspiration and frozen section of palpable mammary lesions. AB - We compared the results of 100 consecutive fine-needle aspirations of palpable mammary lesions in women with 100 consecutive frozen sections done on palpable suspicious nodules in the breasts of women who had had no prior aspiration. There were no false positive results in either group. The false negative rate of aspirations was 6%, compared with none for frozen section, suspicious cases excluded. In four of six patients with false negative aspirations, the specimen was nondiagnostic or unsatisfactory. (In this series, no repeat aspirations were performed for nondiagnostic or negative specimens, even when clinically suspicious.) We conclude that aspiration of a palpable mammary tumor is a definitive procedure with results equivalent to frozen section and equally suitable for choosing and undertaking definitive therapy, when positive. Negative results, viewed in an appropriate clinical context, also proved conclusive. Atypical or suspicious results at aspiration must be followed by repeat aspiration or excision, since these frequently prove positive; likewise, unsatisfactory or nonrepresentative aspirations must be investigated further, as indicated by the clinical evaluation. PMID- 2235983 TI - Medullary carcinoma of the thyroid gland: an encapsulated variant resembling the hyalinizing trabecular (paraganglioma-like) adenoma of thyroid. AB - Two encapsulated medullary carcinomas of the thyroid gland exhibiting an organoid and trabecular pattern with hyalinized stroma and composed of polyhedral to spindled tumor cells with hyaline-appearing cytoplasm are described and compared with three histologically indistinguishable adenomas of follicular cell derivation. Positive immunocytochemical staining for calcitonin and negative staining for thyroglobulin confirms the diagnosis of medullary carcinoma in these tumors, while positive staining for thyroglobulin confirms the follicular cell nature of the adenomas. The distinction between these tumor types is a crucial one, given the prognostic and potential genetic implications of medullary carcinoma. PMID- 2235984 TI - Carcinoembryonic antigen and carcinoids of the gastrointestinal tract. AB - We studied the prognostic significance of immunohistochemically localized carcinoembryonic antigen in 131 nonmetastasizing and 35 metastasizing gastrointestinal carcinoid tumors. The rate of positivity was lower with preabsorbed versus nonabsorbed polyclonal antiserum. Compared with generally used prognostic features (depth of invasion, tumor size, and mitotic rate) positivity for absorbed anticarcinoembryonic antigen was the most specific feature for metastatic tumors but was least sensitive. Although our results demonstrate that anticarcinoembryonic antigen, particularly when absorbed, is highly associated with metastatic disease, depth of invasion and tumor size are better predictors of behavior. PMID- 2235985 TI - Nucleolar organizer regions in human adrenocortical disorders. AB - A silver colloid technique to demonstrate nucleolar organizer region-associated proteins (AgNORs) was performed on sections of 39 human adrenal glands, including normal adrenal cortex, bilateral adrenocortical hyperplasia, adenoma, and carcinoma. In mineralocorticoid and glucocorticoid-producing adrenocortical cells, the mean number of AgNORs per nucleus was lowest in the normal adrenal gland and highest in adenoma, with statistically significant differences. The mean number of AgNORs in bilateral adrenocortical hyperplasia was placed between that of normal adrenal and adenoma. AgNOR numbers in morphologically and clinically verified adrenocortical carcinoma (12 cases) were not different from those in adenoma (17 cases). In adrenal cortex, AgNOR numbers may be correlated with increased steroid hormone production but appear to be of little value in discerning malignancy in adrenocortical neoplasms. PMID- 2235986 TI - Infundibulocystic basal cell carcinoma: a newly described variant. AB - A report by Tozawa and Ackerman (Am J Dermatopathol 9(6):474, 1987) upon a distinctive type of basal cell carcinoma with a particular type of follicular differentiation has stimulated lively correspondence in the literature of dermatopathology. The lesion in question presents itself clinically as a basal cell carcinoma on the face and histopathologically as a neoplasm typified by small size, sharp circumscription, and a unique combination of kinds of follicular differentiation, namely, follicular germs and infundibula. The principal point of contention concerning this neoplasm has been whether it is truly a special variant of basal cell carcinoma or whether it is actually a trichoepithelioma. More extensive studies of this singular neoplasm, including its occurrence in patients with nevoid basal cell carcinoma syndrome, and review of the very few portrayals of it in the literature, have consolidated our view that it is indeed a special variant of basal cell carcinoma. We now present (a) new information about an early stage in the evolution of the neoplasm in point, (b) evidence to validate classification of it as a basal cell carcinoma, and (c) a critical appraisal of other lesions that might pose problems in differential diagnosis. Finally, justification is provided for the designation "infundibulocystic basal cell carcinoma." PMID- 2235987 TI - Monoclonal anti-CEA antibodies in the discrimination between primary pulmonary adenocarcinoma and colon carcinoma metastatic to the lung. AB - Lung metastases from colon adenocarcinoma are often difficult to differentiate from primary lung adenocarcinoma. We studied the diagnostic value of a polyclonal anti-CEA antiserum and two monoclonal anti-CEA antibodies (B18, D14) which define antigens overexpressed in colon carcinoma. Autopsy material from 20 patients with colon carcinoma and lung metastases and 20 specimens from patients with primary lung adenocarcinoma were retrieved, stained, and interpreted without knowledge of the origin of the lung tumor. Colon carcinomas, lung metastases and lung primaries stained positively with polyclonal anti-CEA in 90-100% of cases. D14 stained 75% of colonic metastases and 70% of primary lung adenocarcinomas, whereas 95% of colon primaries were positive. Sixty-five percent of colon primaries and 50% of their metastases were positive with B18, whereas 45% of lung primaries were positive. The frequency of B18 positivity was significantly greater in those colon primaries that were surgically derived (7/9, 78%) compared with their autopsy-derived lung metastases (2/9, 22%) (P less than 0.05). Similarly, D14 staining in surgically derived colon primaries (9/9, 100%) was significantly greater than their autopsy-derived lung metastases (5/9, 56%) (P less than 0.05). In surgical/biopsy-derived tissues 9/9 colonic primaries were D14-positive, whereas only 1 of 6 lung primaries was positive (P = 0.002). We conclude that D14 and polyclonal anti-CEA both stain the majority of colon adenocarcinomas and that changes associated with prolonged fixation may reduce the positivity rate with both B18 and D14 monoclonal antibodies. All three antibodies stain autopsy-derived tissue from primary lung cancer to a significant degree.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235988 TI - The histologic development of acid-induced esophagitis in the cat. AB - Acute reflux esophagitis in man is characterized histologically by infiltrates of segmented leukocytes, epithelial proliferation, and ulcers. Our feline model, which includes each of these features, is produced by the infusion of 0.1 N HCl at a rate of 1 ml per min into the distal esophagus of adult cats for varying periods of time. Our histologic scoring system includes both the intensity and the distribution of four morphologic features, namely basal cell hyperplasia (BCH), intraepithelial segmented leukocytes (IEL), subepithelial leukocytes (SEL), and ulcers. Each of these four categories are scored from 0 to 4, with a potential score of 16. We evaluated the effects of duration of acid exposure by infusing cats with HCl for 5 min (N = 4), 15 min (N = 12), 20 min (N = 12), and 30 min (N = 6), followed by autopsy 24 h later. Mean scores (+/- SE) were as follows: 5 min, 3.0 (+/- 1.7); 15 min, 9.0 (+/- 1.0); 20 min, 11.17 (+/- 1.06); 30 min, 15.17 (+/- 0.54). Differences between 5 and 15 min, 15 and 30 min, and 20 and 30 min were significant (P less than 0.05). Basal cell hyperplasia appeared to be the most sensitive marker of acid injury; ulcers denoted severe injury associated with longer exposure periods. Although an occasional eosinophil was seen, the majority of the segmented leukocytes were neutrophils. We also studied healing histologically by examining cats at 1 d (N = 6), 2 d (N = 6), 3 d (N = 11), and 4 d (N = 6) after a 30 min exposure to HCl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2235989 TI - Identification of human immunodeficiency virus in the heart of a patient with acquired immunodeficiency syndrome. AB - A 35-year-old homosexual white male diagnosed as having human immunodeficiency virus (HIV) infection presented with recurrent pericardial effusion, and HIV was isolated from the pericardial fluid. Autopsy revealed an extensive gross infiltrative lesion in the left ventricle of the heart. Microscopic examination of the myocardium demonstrated multifocal atypical lymphoid cell infiltrations associated with scattered foci of myocardial necrosis. The atypical lymphoid cells were immunoreactive to UCHL-1, a T cell antigen antibody. HIV was immunocytochemically identified in the cardiac lymphocytic infiltrate with anti p24 monoclonal antibodies. This finding was supported by ultrastructural examination and in situ hybridization study. PMID- 2235990 TI - Oligonucleotide probe for herpes virus: use in paraffin sections. AB - A method is described for in situ hybridization detection and typing of herpes simplex virus (HSV) using alkaline phosphatase-labeled synthetic oligonucleotide probes in paraffin tissue sections. Sections mounted on slides are prehybridized and denatured before the probe mixture is added. Hybridization proceeds for 1 h at 60 degrees C. Detection of the alkaline phosphatase label is performed using a nitro blue tetrazolium and 5-bromo-4-chloro-3-indolyl phosphate substrate. Specific hybridization with HSV type 1 DNA was found in sections of herpetic esophagitis and encephalitis. There was no discernible background staining. Hybridization with an oligonucleotide probe specific for HSV type 2 was negative. No hybridization occurred to sections of cytomegalovirus- or adenovirus-infected tissue. The development of this technique expands the utility of synthetic oligonucleotide probes to include hybridization reactions in routinely processed and paraffin-embedded tissue. The use of directly labeled oligonucleotide probes for tissue in situ hybridization overcomes problems of probe contamination with vector plasmid DNA, nonspecific avidin binding to tissue, and the danger and inconvenience of working with radioactive materials. PMID- 2235991 TI - Amphipathic helix motif: classes and properties. PMID- 2235992 TI - Crystal structure of a protein-toxin alpha 1-purothionin at 2.5A and a comparison with predicted models. AB - Alpha 1-Purothionin (alpha 1-P), a wheatgerm protein and lytic toxin, has a secondary and tertiary structure similar to that of crambin as revealed by CD and NMR studies. alpha 1-P crystallizes in the tetragonal space group 1422 with unit cell dimensions: a = b = 53.59 and c = 69.79 A. X-ray diffraction data have been measured to 2.5 A Bragg spacing. The crystal structure has been determined by molecular replacement methods, using an energy-minimized alpha 1-P model structure derived from crambin (Whitlow and Teeter: Journal of Biomolecular Structure and Dynamics 2:831-848, 1985, Journal of the American Chemical Society 108:7163-7172, 1986). The energy-minimized model gives a slightly cleaner rotation solution and better refinement against the x-ray data than do the crambin or unminimized alpha 1-P structures. The final crystallographic residual with the data in the 10-2.5 A resolution range is 0.216. The refined alpha 1-P structure has a backbone rms difference of 0.74 A from crambin and 0.55 A from the energy-minimized alpha 1-P model. A low resolution NMR model of alpha 1-P calculated from metric matrix distance geometry and restrained molecular dynamics differs from crambin's backbone by 2.3 A rms deviation (Clore et al.: EMBO Journal 5:2729-2735, 1986). Backbone dihedral angles for our predicted model differ from the refined alpha 1-P structure in only one region (at a turn where there is a deletion relative to crambin). The NMR model had differences in four regions. PMID- 2235993 TI - Comparison of the structures of globins and phycocyanins: evidence for evolutionary relationship. AB - Globins and phycocyanins are two classes of proteins with different function, different ligands, and no substantial sequence similarity, yet the conformations of their polypeptide chains show very similar folding patterns. Does this arise from a genuine, albeit very distant, evolutionary relationship, or does it represent a common solution of a structural problem? We address this question by a very detailed comparison of the structures of the two protein families. An analysis of the helices and their interactions shows many features common to globins and phycocyanins, including some exceptional features of the globins such as a 3-10 C helix and the unusual "crossed-ridge" packing pattern at the B/E helix interfaces. We conclude that the evidence supports the hypothesis of distant evolutionary relationship between globins and phycocyanins. PMID- 2235994 TI - Conformational flexibility of a scorpion toxin active on mammals and insects: a circular dichroism study. AB - Three scorpion toxins have been analyzed by circular dichroism in water and in 2,2,2-trifluoroethanol (TFE) solutions. These toxins were chosen because they are representative of three kinds of pharmacological activities: (1) toxin AaH IT2, an antiinsect toxin purified from the venom of Androctonus australis Hector, which is able to bind to insect nervous system preparation, (2) toxin Css II, from the venom of Centruroides suffusus suffusus, which is a beta-type antimammal toxin capable of binding to mammal nervous system preparation, and (3) the toxin Ts VII from the venom of Tityus serrulatus, which is able to bind to both types of nervous systems. In order to minimize bias, CD data were analyzed by a predictive algorithm to assess secondary structure content. Among the three molecules, Ts VII presented the most unordered secondary structure in water, but it gained in ordered forms when solubilized in TFE. These results indicated that the Ts VII backbone is the most flexible, which might result in a more pronounced tendency for this toxin molecule to undergo conformational changes. This is consistent with the fact that it competes with both antiinsect and beta-type antimammal toxins for the binding to the sodium channel. PMID- 2235995 TI - Distinct character in hydrophobicity of amino acid compositions of mitochondrial proteins. AB - A compact mitochondrial gene contains all essential information about the synthesis of mitochondrial proteins which play their roles in a small compartment of the mitochondrium. Almost no noncoding regions have been found through the gene, but a necessary set of tRNAs for the 20 amino acids is provided for biosynthesis, some of them coding different amino acids from those in a usual cell. Since the gene is so compact that the produced proteins would have some characteristic aspects for the mitochondrium, amino acid compositions of mitochondrial proteins (mt-proteins) were examined in the 20-dimensional composition space. The results show that compositions of proteins translated from the mitochondrial genes have a distinct character having more hydrophobic content than others, which is illustrated by a clustered distribution in the multidimensional composition space. The cluster is located at the tail edge of the global distribution pattern of a Gaussian shape for other various kinds of proteins in the space. The mt-proteins are rich in hydrophobic amino acids as is a membrane protein, but are different from other membrane proteins in a lesser content of Val. A good correlation found between the base and amino acid compositions for the mitochondria was examined in comparison to those of organisms such as thermophilic bacterium having an extreme G-C-rich base composition. PMID- 2235996 TI - Conformational and helicoidal analysis of the molecular dynamics of proteins: "curves," dials and windows for a 50 psec dynamic trajectory of BPTI. AB - A new procedure for the graphic analysis of molecular dynamics (MD) simulations on proteins is introduced, in which comprehensive visualization of results and pattern recognition is greatly facilitated. The method involves determining the conformational and helicoidal parameters for each structure entering the analysis via the method "Curves," developed for proteins by Sklenar, Etchebest, and Lavery (Proteins: Structure, Function Genet. 6:46-60, 1989) followed by a novel computer graphic display of the results. The graphic display is organized systematically using conformation wheels ("dials") for each torsional parameter and "windows" on the range values assumed by the linear and angular helicoidal parameters, and is present in a form isomorphous with the primary structure per se. The complete time evolution of dynamic structure can then be depicted in a set of four composite figures. Dynamic aspects of secondary and tertiary structure are also provided. The procedure is illustrated with an analysis of a 50 psec in vacuo simulation on the 58 residue protein, bovine pancreatic trypsin inhibitor (BPTI), in the vicinity of the local minimum on the energy surface corresponding to a high resolution crystal structure. The time evolution of 272 conformational and 788 helicoidal parameters for BPTI is analyzed. A number of interesting features can be discerned in the analysis, including the dynamic range of conformational and helicoidal motions, the dynamic extent of 2 degrees structure motifs, and the calculated fluctuations in the helix axis. This approach is expected to be useful for a critical analysis of the effects of various assumptions about force field parameters, truncation of potentials, solvation, and electrostatic effects, and can thus contribute to the development of more reliable simulation protocols for proteins. Extensions of the analysis to present differential changes in conformational and helicoidal parameters is expected to be valuable in MD studies of protein complexes with substrates, inhibitors, and effectors and in determining the nature of structural changes in protein-protein interactions. PMID- 2235998 TI - A somatic gene rearrangement contributing to genetic diversity in maize. AB - We have discovered a somatic genomic rearrangement that occurs at high frequency at a duplicated zein locus in certain cultures of the maize inbred line A188. The rearranged allele arises from the duplication by a two-step process involving a homologous recombination and a second event, which may be a deletion, inversion, or insertion; both steps always occur together. The frequency of rearrangement is lower in homozygous states of the parental allele than in heterozygotes. In both cases, the rearrangement is shown to be mitotic. The rearranged product can be transmitted through meiosis, providing another mechanism for genome evolution in higher eukaryotes. PMID- 2235997 TI - Tension in secretory granule membranes causes extensive membrane transfer through the exocytotic fusion pore. AB - For fusion to occur the repulsive forces between two interacting phospholipid bilayers must be reduced. In model systems, this can be achieved by increasing the surface tension of at least one of the membranes. However, there has so far been no evidence that the secretory granule membrane is under tension. We have been studying exocytosis by using the patch-clamp technique to measure the surface area of the plasma membrane of degranulating mast cells. When a secretory granule fuses with the plasma membrane there is a step increase in the cell surface area. Some fusion events are reversible, in which case we have found that the backstep is larger than the initial step, indicating that there is a net decrease in the area of the plasma membrane. The decrease has the following properties: (i) the magnitude is strongly dependent on the lifetime of the fusion event and can be extensive, representing as much as 40% of the initial granule surface area; (ii) the rate of decrease is independent of granule size; and (iii) the decrease is not dependent on swelling of the secretory granule matrix. We conclude that the granule membrane is under tension and that this tension causes a net transfer of membrane from the plasma membrane to the secretory granule, while they are connected by the fusion pore. The high membrane tension in the secretory granule may be the critical stress necessary for bringing about exocytotic fusion. PMID- 2235999 TI - Structure of visual perception. AB - The response properties of a class of motion detectors (Reichardt detectors) are investigated extensively here. Since the outputs of the detectors, responding to an image undergoing two-dimensional rigid translation, are dependent on both the image velocity and the image intensity distribution, they are nonuniform across the entire image, even though the object is moving rigidly as a whole. To achieve perceptual "oneness" in the rigid motion, we are led to contend that visual perception must take place in a space that is non-Euclidean in nature. We then derive the affine connection and the metric of this perceptual space. The Riemann curvature tensor is identically zero, which means that the perceptual space is intrinsically flat. A geodesic in this space is composed of points of constant image intensity gradient along a certain direction. The deviation of geodesics (which are perceptually "straight") from physically straight lines may offer an explanation to the perceptual distortion of angular relationships such as the Hering illusion. PMID- 2236000 TI - Exogenous mRNA encoding tetanus or botulinum neurotoxins expressed in Aplysia neurons. AB - Injection of exogenous mRNA purified from various tissue preparations into cellular translation systems such as Xenopus oocytes has allowed expression of complex proteins (e.g., receptors for neurotransmitters). No evidence for expression of injected exogenous mRNA, however, has been reported in terminally differentiated neurons. If achieved, it would allow the study of long-lasting changes of properties of nerve cells in their functional context. To obtain evidence of such expression, we chose two proteins that produce a detectable effect even at very low intracellular concentrations. Tetanus toxin and botulinum neurotoxin fulfill this criterion, being the most potent neurotoxins known. Both toxins block neurotransmitter release at nanomolar intracellular concentrations. These di-chain proteins, consisting of a light chain and a heavy chain, have recently been sequenced. Their active sites are located (or partly located) on the light chain. mRNAs encoding the light chain of either toxin were transcribed in vitro from the cloned and specifically truncated genes of Clostridium tetani and Clostridium botulinum, respectively, and injected into presynaptic cholinergic neurons of the buccal ganglia of Aplysia californica. Depression of neurotransmitter release appeared in less than 1 hr, demonstrating successful expression of foreign mRNA injected into a neuron in situ. PMID- 2236001 TI - Isolated dystrophin molecules as seen by electron microscopy. AB - Dystrophin, the protein product of the Duchenne muscular dystrophy locus [Hoffman, E. P., Brown, R. H., Jr., & Kunkel, L. M. (1987) Cell 51, 919-928], is expressed in striated and smooth muscles as well as in non-muscle tissues. Examination of its primary structure has revealed that the molecule is composed of four domains, three of which share many features with the membrane cytoskeletal proteins spectrin and actinin. Dystrophin has thus been predicted to adopt a rod shape [Koenig, M., Monaco, A. P. & Kunkel, L. M. (1988) Cell 53, 219 228]. In the present study, we describe its isolation from the chicken gizzard smooth muscle and present electron microscopic images of the molecule. Polyclonal antibodies were first prepared from a dystrophin fragment derived from the chicken skeletal muscle gene (residues 1173-1728). A dystrophin-enriched membrane preparation from chicken gizzard muscle was then purified by passing it through an affinity chromatography column made with the anti-dystrophin antibodies. Electron microscopy of isolated and rotatory-shadowed dystrophin molecules revealed that the lengths measured for the dystrophin monomers (175 +/- 15 nm) are compatible with a structural arrangement of the repeat sequence segments in triple-barrel alpha-helices connected by short-turn regions, as was earlier postulated for the repeat domains of spectrin and actinin. Electron microscopic images indicate that in addition the dystrophin molecules could present the same capacity of self-association in oligomeric structures as these cytoskeletal proteins and may thus be a part of a complex molecular meshwork essential to muscle cell function. PMID- 2236002 TI - Evolutionary conservation of antigen recognition: the chicken T-cell receptor beta chain. AB - T cells play important regulatory roles in the immune responses of vertebrates. Antigen-specific T-cell activation involves T-cell receptor (TCR) recognition of a peptide antigen presented by a major histocompatibility complex molecule, and much has been learned about this antigen-recognition process through structural and genetic studies of mammalian TCRs. Although previous studies have demonstrated that avian T cells express cell-surface molecules analogous to the mammalian TCR heterodimers, TCR genes have not been identified in nonmammalian species. We now report the cloning of a cDNA that encodes the beta chain of the chicken TCR. Southern blot analysis using this TCR beta cDNA probe demonstrated that the chicken TCR beta locus was clonally rear-ranged in chicken T-cell lines. TCR beta mRNA was expressed in cells isolated from the thymus but not in cells from the bursa of Fabricius where B cells are generated. Sequence analysis of six additional TCR beta cDNAs suggested the existence of at least two variable (V) region families, three joining (J) elements, and single diversity (D) and constant (C) elements. As in mammals, considerable nucleotide diversity was observed at the junctions of the variable, diversity, and joining elements in chicken TCR beta cDNAs. Genomic V beta and J beta elements were also cloned and sequenced. Both elements are flanked by classical heptamer/nonamer recombination signal sequences. Although the chicken and mammalian TCR beta chains displayed only 31% overall amino acid sequence identity, a number of conserved structural features were observed. These data indicate that (i) the chicken TCR beta repertoire is generated by combinatorial and junctional diversity and (ii) despite divergent evolution at the level of nucleotide sequence, important structural features of the TCR beta polypeptide are conserved between avian and mammalian species. PMID- 2236004 TI - Estrogen receptor level determines sex-specific in vitro transcription from the Xenopus vitellogenin promoter. AB - Female-specific expression of the Xenopus laevis vitellogenin gene was reconstituted in vitro by addition of recombinant vaccinia-virus-produced estrogen receptor to nuclear extracts from male livers, in which this gene is silent. Transcription enhancement was at least 30 times and was selectively restricted to vitellogenin templates containing the estrogen-responsive unit. Thus, in male hepatocytes, estrogen receptor is the limiting regulatory factor that in the female liver controls efficient and accurate sex-specific expression of the vitellogenin gene. Furthermore, the Xenopus liver factor B, which is essential in addition to the estrogen receptor for the activation of this gene, was successfully replaced in the Xenopus extract by purified human nuclear factor I, identifying factor B of Xenopus as a functional homolog of this well characterized human transcription factor. PMID- 2236003 TI - Aberrant splicing of androgen receptor mRNA results in synthesis of a nonfunctional receptor protein in a patient with androgen insensitivity. AB - Androgen insensitivity is a disorder in which the correct androgen response in an androgen target cell is impaired. The clinical symptoms of this X chromosome linked syndrome are presumed to be caused by mutations in the androgen receptor gene. We report a G----T mutation in the splice donor site of intron 4 of the androgen receptor gene of a 46,XY subject lacking detectable androgen binding to the receptor and with the complete form of androgen insensitivity. This point mutation completely abolishes normal RNA splicing at the exon 4/intron 4 boundary and results in the activation of a cryptic splice donor site in exon 4, which leads to the deletion of 123 nucleotides from the mRNA. Translation of the mutant mRNA results in an androgen receptor protein approximately 5 kDa smaller than the wild type. This mutated androgen receptor protein was unable to bind androgens and unable to activate transcription of an androgen-regulated reporter gene construct. This mutation in the human androgen receptor gene demonstrates the importance of an intact steroid-binding domain for proper androgen receptor functioning in vivo. PMID- 2236006 TI - Effect of specific mutations of tyrosine-(M)210 on the primary photosynthetic electron-transfer process in Rhodobacter sphaeroides. AB - We have measured the rate of the initial electron-transfer process as a function of temperature in reaction centers in a native strain of the photosynthetic bacterium Rhodobacter sphaeroides and two mutants generated by site-directed mutagenesis. In the mutants, a tyrosine residue in the vicinity of the primary electron donor and acceptor molecules was replaced by either phenylalanine or isoleucine. The electron-transfer reaction is slower in the mutants and has a qualitatively different dependence on temperature. In native reaction centers the rate increases as the temperature is reduced, in the phenylalanine mutant it is virtually independent of temperature, and in the isoleucine mutant it decreases with decreasing temperature. At 77 K, the electron-transfer reaction is approximately 30 times slower in the isoleucine mutant than in the native. These observations support the view that tyrosine-(M)210 plays an important role in the electron-transfer mechanism. In the isoleucine mutant at low temperatures, the stimulated emission from the excited reaction center undergoes a time-dependent shift to shorter wavelengths. PMID- 2236005 TI - DNA mismatch repair in Xenopus egg extracts: repair efficiency and DNA repair synthesis for all single base-pair mismatches. AB - Repair of all 12 single base-pair mismatches by Xenopus egg extracts was measured by a physical assay with a sequence containing four overlapping restriction sites. The heteroduplex substrates, derivatives of M13 phage DNA, differed in sequence at the mismatch position only and permitted measurement of repair to both strands. The efficiency of repair varied about 4-fold between the most and least effectively repaired mismatches. Repair was most active with C/A and T/C mismatches but the efficiency varied depending on the orientation of the mismatch. Mismatch-specific DNA repair synthesis was also observed but the extent of repair was not always predictive of the extent of synthesis, suggesting the presence of different repair systems or different modes of mismatch recognition. PMID- 2236007 TI - Steady-state force-velocity relation in the ATP-dependent sliding movement of myosin-coated beads on actin cables in vitro studied with a centrifuge microscope. AB - To eliminate the gap between the biochemistry of actomyosin in solution and the physiology of contracting muscle, we developed an in vitro force-movement assay system in which the steady-state force-velocity relation in the actin-myosin interaction can be studied. The assay system consists of the internodal cells of an alga, Nitellopsis obtusa, containing well-organized actin filament arrays (actin cables); tosyl-activated polystyrene beads (diameter, 2.8 microns; specific gravity, 1.3) coated with skeletal muscle myosin; and a centrifuge microscope equipped with a stroboscopic light source and a video system. The internodal cell preparation was mounted on the rotor of the centrifuge microscope, so that centrifugal forces were applied to the myosin-coated beads moving along the actin cables in the presence of ATP. Under constant centrifugal forces directed opposite to the bead movement ("positive" loads), the beads continued to move with constant velocities, which decreased with increasing centrifugal forces. The steady-state force-velocity curve thus obtained was analogous to the double-hyperbolic force-velocity curve of single muscle fibers. The unloaded velocity of bead movement was 1.6-3.6 microns/s (20-23 degrees C), while the maximum "isometric" force generated by the myosin molecules on the bead was 1.9-39 pN. If, on the other hand, the beads were subjected to constant centrifugal forces in the direction of bead movement ("negative" loads), the bead also moved with constant velocities. Unexpectedly, the velocity of bead movement did not increase with increasing negative loads but first decreased by 20-60% and then increased towards the initial unloaded velocity until the beads were eventually detached from the actin cables. PMID- 2236008 TI - Induction of verotoxin sensitivity in receptor-deficient cell lines using the receptor glycolipid globotriosylceramide. AB - Verotoxin 1 is an Escherichia coli-derived subunit toxin that specifically binds to the glycolipid globotriosylceramide and is cytotoxic for cells that contain this plasma membrane glycolipid. Glycolipid incorporation experiments have now been performed using human lymphoid cells of the B lineage that lack this receptor, to conclusively demonstrate that globotriosylceramide alone is a functional receptor for this toxin. Globotriosylceramide incorporated into the membrane of toxin-resistant cells provides intracellular access to verotoxin by receptor-mediated endocytosis. Protein synthesis is then inhibited and globotriosylceramide-containing cells are killed. PMID- 2236009 TI - Epithelins 1 and 2: isolation and characterization of two cysteine-rich growth modulating proteins. AB - Two proteins, termed epithelin 1 and epithelin 2, that inhibit the growth of A431 cells, derived from a human epidermal carcinoma of the vulva, have been purified from rat kidney. Epithelin 1 stimulates the proliferation of murine keratinocytes, whereas epithelin 2 inhibits the epithelin 1-elicited growth of these cells. Thus epithelin 1 and 2 behave as agonist and antagonist, respectively, for normal epithelial cells. Epithelins are low molecular mass (approximately 6 kDa), acid- and heat-stable, single-chain proteins containing approximately 20% cysteine. Some of these cysteines form disulfide linkage(s) that are essential for biological activity. The amino-terminal amino acid sequences of epithelin 1 and epithelin 2 have been determined. The two proteins showed no substantial sequence homology with other proteins. However, a significant homology was seen between the amino-terminal sequences of epithelin 1 and epithelin 2. Epithelins 1 and 2, therefore, appear to represent members of a distinct family of growth regulators. PMID- 2236010 TI - Parallel zippers formed by alpha-helical peptide columns in crystals of Boc-Aib Glu(OBzl)-Leu-Aib-Ala-Leu-Aib-Ala-Lys(Z)-Aib-OMe. AB - The crystal structure of the decapeptide Boc-Aib-Glu(OBzl)-Leu-Aib-Ala-Leu-Aib Ala-Lys(Z)-Aib-OMe (where Aib is alpha-aminoisobutyryl, Boc is t-butoxycarbonyl, OBzl is benzyl ester, and Z is benzyloxycarbonyl) illustrates a parallel zipper arrangement of interacting helical peptide columns. Head-to-tail NH...OC hydrogen bonding extends the alpha-helices formed by the decapeptide into long columns in the crystal. An additional NH...OC hydrogen bond in the head-to-tail region, between the extended side chains of Glu(OBzl), residue 2 in one molecule, and Lys(Z), residue 9 in another molecule, forms a "double tooth" on the side of the column. These double teeth are repeated regularly on the helical columns with spaces of six residues between them (approximately 10 A). The double teeth on a pair of parallel columns (all carbonyl groups pointed in the same direction) interdigitate in a zipper motif. All contacts in the zipper portion are of the van der Waals type. The peptide, with formula C66H103N11O17.H2O, crystallizes in space group P2(1)2(1)2(1) with a = 10.677(4) A, b = 16.452(6) A, and c = 43.779(13) A; overall agreement R = 10.2% for 3527 observed reflections (magnitude of /F0/ greater than 3 sigma); resolution 0.9 A. PMID- 2236011 TI - Selection of gamma delta T cells with canonical T-cell antigen receptors in fetal thymus. AB - Two gamma delta T-cell subsets that are generated in the fetal thymus and selectively localize in epidermis and uterus-vagina-tongue epithelia exhibit remarkable homogeneity in their (T-cell) antigen receptors (TCR). In the present study, we show that cells expressing the canonical gamma delta TCR are also generated in fetal thymus organ cultures. Treatment of these cultures with anti gamma delta TCR antibodies did not prevent gamma delta T-cell development but led to a striking increase in the frequency of noncanonical in-frame sequences. We conclude from this finding that cells expressing the canonical TCR accumulate selectively as a result of TCR-mediated positive selection in the fetal thymus. PMID- 2236013 TI - Endogenous gibberellins in Arabidopsis thaliana and possible steps blocked in the biosynthetic pathways of the semidwarf ga4 and ga5 mutants. AB - Twenty gibberellins (GAs) have been identified in extracts from shoots of the Landsberg erecta line of Arabidopsis thaliana by full-scan gas chromatography mass spectrometry and Kovats retention indices. Eight of them are members of the early-13-hydroxylation pathway (GA53, GA44, GA19, GA17, GA20, GA1, GA29, and GA8), six are members of the early-3-hydroxylation pathway (GA37, GA27, GA36, GA13, GA4, and GA34), and the remaining six are members of the non-3,13 hydroxylation pathway (GA12, GA15, GA24, GA25, GA9, and GA51). Seven of these GAs were quantified in the Landsberg erecta line of Arabidopsis and in the semidwarf ga4 and ga5 mutants by gas chromatography-selected ion monitoring (SIM) using internal standards. The relative levels of the remaining 13 GAs were compared by the use of ion intensities only. In comparison with the Landsberg erecta line, the ga4 mutant had reduced levels of the 3-hydroxy- and 3,13-dihydroxy-GAs, and it accumulated the 13-hydroxy-GAs, except GA53, and the non-3,13-hydroxy-GAs, except GA12. The GA4 gene encodes, therefore, a protein with 3 beta-hydroxylation activity. The ga5 mutant had reduced levels of the C19-GAs, which indicates that the product of the GA5 gene catalyzes the elimination of C-20 at the aldehyde level. The ga5 mutant also had increased levels of certain C20-GAs, which indicates existence of an additional control, possibly hydroxylation of C-20. The growth-response data, as well as the accumulation of GA9 in the ga4 mutant, indicate that GA9 is not active in Arabidopsis, but it must be 3 beta hydroxylated to GA4 to become bioactive. It is concluded that the reduced levels of the 3 beta-hydroxy-GAs, GA1 and GA4, are the cause of the semidwarf growth habit of both mutants. PMID- 2236012 TI - The general mitochondrial matrix processing protease from rat liver: structural characterization of the catalytic subunit. AB - A critical step in the import of nuclear-encoded precursor proteins into mitochondria involves proteolytic cleavage of their amino-terminal leader peptides by processing proteases found in the mitochondrial matrix. We report here the characterization of the general matrix processing protease from rat liver mitochondria. The final enzyme preparation consisted of two polypeptides, a catalytically active 55-kDa subunit and a 52-kDa one. To deduce the complete primary structure of the 55-kDa subunit, we first sequenced its mature amino terminus and several tryptic peptides derived from the pure protein. Next, using mixed oligonucleotide primers that had sequences based on two of these peptides, we synthesized a partial cDNA probe by selective amplification of liver RNA with the polymerase chain reaction. The amplified probe was then used to obtain a nearly full-length clone from a rat liver cDNA library. This cDNA codes for 508 amino acid residues, including 16 residues of an amino-terminal leader peptide, the cleavage site of which is located two polypeptide bonds downstream from an arginine residue. The mature portion has a predicted molecular mass of 55.2 kDa; it shows 36% identity with the mitochondrial processing peptidases of Saccharomyces cerevisiae and Neurospora crassa. A conserved structural feature is a putative, negatively charged alpha-helix, located in the amino-terminal half of the subunit; this element might be important for the recognition of positively charged leader peptides characteristic of mitochondrial precursor proteins. PMID- 2236014 TI - Central prolactin infusions stimulate maternal behavior in steroid-treated, nulliparous female rats. AB - A series of experiments were conducted to determine whether and under what conditions central prolactin (PRL) administration would stimulate the onset of maternal behavior in female rats and to identify possible neural sites of PRL action. In each experiment ovariectomized, nulliparous rats whose endogenous PRL levels were suppressed with bromocriptine were tested for maternal behavior toward foster young. In experiments 1, 2, and 4, females were also exposed to pregnancy-like levels of progesterone (days 1-11) followed by estradiol (days 11 17). In experiment 1 infusions (days 11-13) of four doses of ovine PRL (400 ng, 2 micrograms, 10 micrograms, or 50 micrograms, but not 80 ng) into the lateral ventricle resulted in a rapid onset of maternal behavior (behavioral testing, days 12-17). The stimulatory action of these doses of PRL appears to be central, since subcutaneous injections of 50 micrograms of ovine PRL failed to affect maternal responsiveness (experiment 2). Experiment 3 indicated that the stimulatory effect of intracerebroventricularly administered PRL is steroid dependent. Infusions of either 10 micrograms of ovine PRL or 10 micrograms of rat PRL failed to induce maternal behavior in nonsteroid-treated animals. In the final experiment (no. 4) bilateral infusions of 40 ng of ovine PRL into the medial preoptic area of steroid-treated rats resulted in a pronounced stimulation of maternal behavior. These findings demonstrate a central site of PRL action in the stimulation of maternal responsiveness and point to the medial preoptic area as a key neural site for PRL regulation of maternal behavior. PMID- 2236015 TI - Location of the cis-acting auxin-responsive region in the promoter of the par gene from tobacco mesophyll protoplasts. AB - We have isolated a genomic clone of an auxin-regulated par gene, which is expressed during the transition from G0 phase to S phase in the early stage of tobacco mesophyll protoplasts cultured in vitro, from a tobacco genomic library using the par cDNA as a probe. When a chimeric gene, in which a reporter gene for bacterial beta-glucuronidase (GUS) was placed downstream of the 5' flanking sequences of the par gene, was introduced into tobacco mesophyll protoplasts by electroporation, the chimeric gene elicited auxin-regulated expression of GUS activity. Because deletion of a 111-base-pair (bp) direct repeat in the 5' flanking sequences of the par gene abolished the auxin-induced GUS activity, it is deduced that in the 111-bp direct repeat of the par gene promoter is localized an auxin-responsive region, which regulates auxin-mediated activation of transcription. PMID- 2236016 TI - Gangliosides normalize distorted single-cell intracellular free Ca2+ dynamics after toxic doses of glutamate in cerebellar granule cells. AB - Glutamate-induced delayed neurotoxicity after abusive and paroxismal activation of its receptors has been proposed to depend upon a sustained increase in intracellular free Ca2+ [( Ca2+]i). To elucidate the temporal and causal relationship between glutamate-induced changes in [Ca2+]i and neuronal death, we simultaneously studied the dynamics of [Ca2+]i changes in single neurons with the acetoxymethyl ester of fura-2 and the cell viability by imaging the nuclear penetration of propidium iodide. The main difference between toxic (50 microM) and nontoxic (5 microM) doses of glutamate is the lack of regulation in [Ca2+]i 20 min after glutamate is removed. This protracted rise in [Ca2+]i in a single cell is correlated with (r = 0.87, P less than 0.01, Spearman's test), and consequently predictive of, the time of appearance of neuronal death, as measured by propidium iodide fluorescence. In addition, the glutamate receptor antagonists dibenzocyclohepteneimine (MK-801) and 3,3-(2-carboxypiperazine-4-yl)propyl 1 phosphate reduce the acute increase of [Ca2+]i induced by glutamate but fail to revert the protracted increase of [Ca2+]i, elicited by toxic doses of glutamate. In contrast, the ganglioside GM1 and the semisynthetic lysoGM1 with N acetylsphingosine (LIGA-4) and lysoGM1 with N-dichloroacetylsphingosine (LIGA-20) failed to change the immediate rise of [Ca2+]i elicited by glutamate but prevented the protracted increase in [Ca2+]i after toxic doses of glutamate. Voltage-dependent Ca2+ channel blockers (nifedipine, etc.) did not change the initial or protracted responses to glutamate. PMID- 2236017 TI - Long-range movement and fibril association of type X collagen within embryonic cartilage matrix. AB - A recent immunoelectron microscopic study of type X collagen in developing cartilage gave results that could be explained by movement of the molecule from one region of the cartilage matrix to another, there becoming associated with preexisting collagen fibrils. In the present study, to test the feasibility of this model we incubated pieces of nonhypertrophic, embryonic chicken sternal cartilage (which has no endogenous type X collagen) in medium with type X collagen and then used immunofluorescence and immunoelectron microscopy to evaluate movement of the molecule through the matrix. The results show that type X collagen molecules can indeed pass through embryonic sternal cartilage matrix and subsequently become fibril-associated. PMID- 2236018 TI - Molecular cloning of a human gene that is a member of the nerve growth factor family. AB - Cell death within the developing vertebrate nervous system is regulated in part by interactions between neurons and their innervation targets that are mediated by neurotrophic factors. These factors also appear to have a role in the maintenance of the adult nervous system. Two neurotrophic factors, nerve growth factor and brain-derived neurotrophic factor, share substantial amino acid sequence identity. We have used a screen that combines polymerase chain reaction amplification of genomic DNA and low-stringency hybridization with degenerate oligonucleotides to isolate human BDNF and a human gene, neurotrophin-3, that is closely related to both nerve growth factor and brain-derived neurotrophic factor. mRNA products of the brain-derived neurotrophic factor and neurotrophin-3 genes were detected in the adult human brain, suggesting that these proteins are involved in the maintenance of the adult nervous system. Neurotrophin-3 is also expected to function in embryonic neural development. PMID- 2236019 TI - Cleavage of the bacteriophage P1 packaging site (pac) is regulated by adenine methylation. AB - The packaging of bacteriophage PI DNA is initiated when the phage packaging site (pac) is recognized and cleaved and continues until the phage head is full. We have previously shown that pac is a 162-base-pair segment of P1 DNA that contains seven DNA adenine methyltransferase methylation sites (5'-GATC). We show here that cleavage of pac is methylation sensitive. Both in vivo and in vitro experiments indicate that methylated pac is cleavable, whereas unmethylated pac is not. Moreover, DNA isolated from P1 phage and containing an uncut pac site was a poor substrate for in vitro cleavage until it was methylated by the Escherichia coli DNA adenine methyltransferase. Comparison of that uncut pac DNA with other viral DNA fragments by digestion with methylation-sensitive restriction enzymes indicated that the uncut pac DNA was preferentially undermethylated. In contrast, virion DNA containing a cut pac site was not undermethylated. We believe these results indicate that pac cleavage is regulated by adenine methylation during the phage lytic cycle. PMID- 2236020 TI - The human immunodeficiency virus type 2 vpr gene is essential for productive infection of human macrophages. AB - The human immunodeficiency virus (HIV) genetic determinant(s) responsible for tropism in human T cells or macrophages are not well defined. We studied the role of the HIV type 2 (HIV-2) nef and vpr genes in viral tropism. HIV-2 mutants, lacking either vpr or nef genes, or both vpr and nef, were obtained by site specific mutagenesis of a biologically active HIV-2 proviral clone (HIV 2sbl/isy), which is infectious in both human T cells and macrophages. Viral progeny carrying mutations of nef, vpr, or of both nef and vpr genes replicated more efficiently than the parental virus in primary human peripheral blood cells and in the human Hut 78 T-cell line. In contrast, the HIV-2 nef- mutant infected human macrophages as efficiently as the parental virus, whereas viruses lacking the vpr gene either alone or in conjunction with the lack of the nef gene did not replicate in macrophages. Thus, some lack of nef in HIV-2 enhances viral replication in T cells and does not interfere with viral replication in primary macrophages, whereas vpr is essential for replication of HIV-2 in human macrophages. Because the parental HIV-2sbl/isy cloned virus also infects rhesus macaques, the use in animal studies of these HIV-2 mutants with differences in cell tropism and rates of replication will be highly useful in understanding the mechanism of viral infectivity and possibly pathogenicity in vivo. PMID- 2236021 TI - Expression of CD4 by human megakaryocytes. AB - The CD4 antigen, which serves as the receptor for human immunodeficiency virus type 1 (HIV-1) on T cells, has been detected on human megakaryocytes. Recent evidence of impaired thrombopoiesis in HIV-1-related thrombocytopenia suggested that these cells could be directly infected by the virus and prompted a search for a receptor on megakaryocytes of normal subjects that could permit entry of HIV-1. Bone marrow specimens from uninfected normal control subjects were centrifuged over Ficoll-Hypaque (1.077 g/ml) and analyzed by three-color analysis with a flow cytometer utilizing monoclonal antibodies against CD4 and a glycoprotein present on the surface of megakaryocytes and platelets (GPIIb/IIIa; CD41), as well as 7-aminoactinomycin D, a stain for DNA. Cells presumed to be megakaryocytes were identified by having a DNA content greater than tetraploid and staining brightly with anti-CD41. Approximately 0.4% of the nucleated cells of the marrow met these criteria. Twenty-five percent of these megakaryocytes stained as brightly as CD4+ T cells. Several clones of antibody recognizing different epitopes of the CD4 molecule gave similar results. Platelets were CD4-. Staining of megakaryocytes with anti-CD4 was confirmed by direct microscopic examination of Percoll-gradient-enriched megakaryocytes employing two-color (CD4 phycoerythrin and CD41-fluorescein) immunofluorescence analysis and phase contrast microscopy. The proportion of double-labeled cells among 112 phase contrast-identifiable megakaryocytes from five bone marrow specimens varied between 20% and 26% with a mean and SD of 22% +/- 2.5%. Thus some human megakaryocytes express CD4 on their surface that should be capable of binding the HIV-1 gp120 envelope protein. This could serve as a portal of entry for HIV-1. PMID- 2236022 TI - Myb protein binds to human immunodeficiency virus 1 long terminal repeat (LTR) sequences and transactivates LTR-mediated transcription. AB - The protooncogene c-myb encodes a nuclear transcription factor that binds to DNA in a sequence-specific manner and transactivates transcription of several viral and cellular genes. The expression of c-myb is induced in mitogen-stimulated peripheral blood lymphocytes and is constitutively expressed in several CD4+ T cell and myeloid cell lines, all of which constitute excellent targets for human immunodeficiency virus (HIV) infection and replication. We looked for the presence of Myb-binding motifs in human retroviral long terminal repeats (LTRs) and tested for Myb binding to HIV-1 LTR sequences by using a highly purified recombinant Myb protein. Our results show that HIV-1 LTR contains one high affinity Myb-binding site along with two or more low-affinity binding sites. DNase I protection analysis as well as oligonucleotide competition experiments indicate that this binding is sequence specific. Introduction of purified Myb protein directly into HeLa cells harboring HIV-1 LTR chloramphenicol acetyltransferase vectors indicates that Myb protein transactivates HIV-1 LTR mediated transcription. Thus, Myb protein binding to HIV LTR sequences may constitute one of the signals that regulates HIV-1 transcription. PMID- 2236023 TI - Steroids induce acetylcholine receptors on cultured human muscle: implications for myasthenia gravis. AB - Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. We show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. Our results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also to a direct effect on muscle. We propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications. PMID- 2236024 TI - Genetically engineered truncated myosin in Dictyostelium: the carboxyl-terminal regulatory domain is not required for the developmental cycle. AB - The study of engineered Dictyostelium mutants with altered or missing myosin has revealed the molecule to be essential both for cytokinesis and for completion of the complex Dictyostelium developmental cycle. To explore the biological role of the carboxyl-terminal portion of the myosin tail, we have created a Dictyostelium cell line bearing a mutation designated my delta C34 in the myosin (mhcA) locus. This cell line produces a truncated myosin protein lacking the 34-kDa carboxyl terminus of the wild-type tail. Southern blots of the mutant cells show that the myosin gene was disrupted by homologous recombination of the transforming plasmid into the myosin locus. Based on in vitro studies of myosin functional domains, the 200-kDa truncated myosin was designed to include a domain important for assembly but to eliminate a domain important for threonine phosphorylation. The mutant cells are defective in cytokinesis, similar to those mutants that are either devoid of myosin (null cells) or contain a truncated 140-kDa myosin (hmm cells). However, unlike previous mutants, the cells carrying the my delta C34 mutation are able to complete the Dictyostelium developmental cycle to form fruiting bodies. Thus a truncated 200-kDa myosin can substitute for native myosin to function in developing cells. These results demonstrate that the 34-kDa carboxyl terminus of myosin, which contributes regulated phosphorylation sites and 20% of the total length of the rod, is not required for the developmental cycle of Dictyostelium. PMID- 2236025 TI - Interaction of epsilon-globin cis-acting control elements with erythroid-specific regulatory macromolecules. AB - We have used a competition assay to investigate the influence of erythroid specific cellular factors on transcription from the human epsilon-globin major cap site promoter and the minor promoter located 200 base pairs (bp) upstream from the epsilon-globin cap site. In the human erythroid cell line K562, competition of the epsilon-globin major cap site promoter linked to the chloramphenicol acetyltransferase (CAT) gene (epsilon P-CAT) with the same promoter fragment linked to a neomycin resistance gene (epsilon P-NEO) leads to a reduction in CAT activity. This indicates the specific presence of K562 cells of factor(s) which interact with the 200-bp promoter fragment (isolated from the gene body or flanking sequences) to activate transcription from the epsilon globin major cap site. Competition of the epsilon-globin major promoter (as epsilon P-CAT) with the upstream minor epsilon-globin promoter (as epsilon P2 NEO) also leads to a reduction in CAT activity, indicating that both promoters share erythroid-specific trans-acting factors. The reverse competition (epsilon P2-CAT with epsilon P-NEO) leads to an increase in CAT activity, suggesting that the existence of erythroid-specific factor(s) which repress transcription from the 200-bp-upstream epsilon-globin promoter. PMID- 2236026 TI - Opal phytoliths found on the teeth of the extinct ape Gigantopithecus blacki: implications for paleodietary studies. AB - Identification of opal phytoliths bonded to the enamel surface of the teeth of Gigantopithecus blacki indicates that this extinct ape had a varied diet of grasses and fruits. By using the scanning electron microscope at magnifications of 2000-6000x specific opal phytoliths were observed and photographed on the fossilized teeth of an extinct species. Since opal phytoliths represent the inorganic remains of once-living plant cells, their documentation on the teeth of Gigantopithecus introduces a promising technique for the determination of diet in extinct mammalian species which should find numerous applications in the field of paleoanthropology as well as vertebrate paleontology. PMID- 2236027 TI - Human colorectal cancers display abnormal Fourier-transform infrared spectra. AB - Fourier-transform infrared spectroscopy (FT-IR) was applied to the study of tissue sections of human colorectal cancer. Pairs of tissue samples from colorectal cancer and histologically normal mucosa 5-10 cm away from the tumor were obtained from 11 patients who underwent partial colectomy. All cancer specimens displayed abnormal spectra compared with the corresponding normal tissues. These changes involved the phosphate and C-O stretching bands, the CH stretch region, and the pressure dependence of the CH2 bending and C = O stretching modes. Our findings indicate that in colonic malignant tissue, there are changes in the degree of hydrogen-bonding of (i) oxygen atoms of the backbone of nucleic acids (increased); (ii) OH groups of serine, tyrosine, and threonine residues (any or all of them) of cell proteins (decreased); and (iii) the C = O groups of the acyl chains of membrane lipids (increased). In addition, they indicate changes in the structure of proteins and membrane lipids (as judged by the changes in their ratio of methyl to methylene groups) and in the packing and the conformational structure of the methylene chains of membrane lipids. The cell(s) of the malignant colon tissues responsible for these spectral abnormalities is unknown. Cultured colon adenocarcinoma cell lines displayed similarly abnormal FT-IR spectra. The diagnostic potential of the observed changes is discussed. PMID- 2236028 TI - When is an inhibitory synapse effective? AB - Interactions between excitatory and inhibitory synaptic inputs on dendrites determine the level of activity in neurons. Models based on the cable equation predict that silent shunting inhibition can strongly veto the effect of an excitatory input. The cable model assumes that ionic concentrations do not change during the electrical activity, which may not be a valid assumption, especially for small structures such as dendritic spines. We present here an analysis and computer simulations to show that for large Cl- conductance changes, the more general Nernst-Planck electrodiffusion model predicts that shunting inhibition on spines should be much less effective than that predicted by the cable model. This is a consequence of the large changes in the intracellular ionic concentration of Cl- that can occur in small structures, which would alter the reversal potential and reduce the driving force for Cl-. Shunting inhibition should therefore not be effective on spines, but it could be significantly more effective on the dendritic shaft at the base of the spine. In contrast to shunting inhibition, hyperpolarizing synaptic inhibition mediated by K+ currents can be very effective in reducing the excitatory synaptic potentials on the same spine if the excitatory conductance change is less than 10 nS. We predict that if the inhibitory synapses found on cortical spines are to be effective, then they should be mediated by K+ through GABAB receptors. PMID- 2236029 TI - The C'-terminal interaction domain of the thyroid hormone receptor confers the ability of the DNA site to dictate positive or negative transcriptional activity. AB - To investigate mechanisms responsible for positive and negative transcriptional control, we have utilized two types of promoters that are differentially regulated by thyroid hormone (T3) receptors. Promoters containing the palindromic T3 response element TCAGGTCA TGACCTGA are positively regulated by the T3 receptor after the administration of T3, whereas otherwise identical promoters containing the estrogen response element TCAGGTCA CTG TGACCTGA can be regulated negatively; converse effects are observed with the estrogen receptor. We describe evidence that the transcriptional inhibitory effects of the T3 or estrogen receptors on the estrogen or T3 response elements, respectively, are imposed by amino acid sequences in the C'-terminal region that colocalize with dimerization and hormone binding domains and that these sequences can transfer inhibitory functions to other classes of transcription factors. Removal of the C'-terminal dimerization and hormone-binding domains of either the alpha T3 or estrogen receptors permits each receptor to act constitutively to enhance transcription on both T3 and estrogen response elements. It is, therefore, suggested that protein-protein interactions between receptor C' termini limit the subset of DNA binding sites on which transcriptional activation occurs. PMID- 2236030 TI - Direct measurement of oligonucleotide substrate binding to wild-type and mutant ribozymes from Tetrahymena. AB - Like protein enzymes, RNA enzymes (ribozymes) provide specific binding sites for their substrates. We now show that equilibrium dissociation constants for complexes between the Tetrahymena ribozyme and its RNA substrates and products can be directly measured by electrophoresis in polyacrylamide gels containing divalent cations. Binding is 10(3)- to 10(4)-fold tighter (4-5 kcal/mol at 42 degrees C) than expected from base-pairing interactions alone, implying that tertiary interactions also contribute to energetic stabilization. Binding decreases with single base changes in the substrate, substitution of deoxyribose sugars, and lower Mg2+ concentration. Ca2+, which enables the ribozyme to fold but is unable to mediate efficient RNA cleavage, promotes weaker substrate binding than Mg2+. This indicates that Mg2+ has special roles in both substrate binding and catalysis. Mutagenesis of a region near the internal guide sequence disrupts substrate binding, whereas binding is not significantly affected by a mutation of the guanosine-binding site. This approach should be generally useful for analysis of ribozyme variants independent of their catalytic activities. PMID- 2236031 TI - Splicing of COB intron 5 requires pairing between the internal guide sequence and both flanking exons. AB - Group I introns are characterized by a set of conserved sequence elements and secondary structures. Evidence supporting the pairing of certain of these sequences has come from the comparison of intron sequences and from the analysis of mutations that disrupt splicing by interfering with pairing. One of the structures proposed for all group I introns is an internal guide sequence that base pairs with the upstream and the downstream exons, bringing them into alignment for ligation. We made specific mutations in the internal guide sequence and the flanking exons of the fifth intron in the yeast mitochondrial gene for apocytochrome b (COB). Mutations that disrupted the pairing between the internal guide sequence and the upstream exon (the P1 pairing) blocked addition of guanosine to the 5' end of the intron during autocatalytic reactions and prevented formation of the full-length circular intron. In contrast, transcripts containing mutations that disrupted the pairing between the guide sequence and the downstream exon (the P10 helix) initiated splicing but failed to ligate exons. Compensatory mutations that restored helices of normal stability mitigated the effects of the original mutations. These data provide direct evidence for the importance of the base pairing between the internal guide sequence and the downstream exon in the splicing of a wild-type group I intron. PMID- 2236032 TI - Early folding intermediate of ribonuclease A. AB - Pulsed hydrogen exchange (2H-1H) is used to characterize the folding process of ribonuclease A (disulfide bonds intact). The results show one principal early folding intermediate (I1), which is formed rapidly after the start of folding and whose proton-exchange properties change with the time of folding. All probes that are hydrogen bonded within the beta-sheet of native ribonuclease A are protected in I1. Thus, the results suggest that the beta-sheet is formed rapidly and cooperatively. The initial protection factors of probes in the beta-sheet are between 10 and 100, but they increase with time of folding and exceed 1000 at 400 msec from the start of folding. Thus, the beta-sheet is only moderately stable when it is first formed, but subsequent events stabilize it, possibly through interactions involving hydrophobic side chains. The large protection factors of the beta-sheet probes in an early folding intermediate are unexpected and remarkable. Probes in the three alpha-helices are fewer in number and give less accurate data than the beta-strand probes. The folding kinetics expected for a simple sequential model of folding are outlined. An important difference between the observed and predicted behavior is that the early folding intermediate is not fully populated when it is first formed. PMID- 2236033 TI - Interchangeable RNA polymerase I and II enhancers. AB - The RNA polymerase I (pol I) enhancer of Saccharomyces cerevisiae contains at least three elements commonly associated with RNA polymerase II (pol II) enhancers, binding sites for the transcriptional activators general regulatory factor 2 and autonomously replicating sequence-binding factor I, and a thymidine rich element. When the particular form of the thymidine-rich element found in the pol I enhancer was placed in front of a pol II promoter, transcription was stimulated 43-fold, comparable to the effect of a powerful pol II activator such as Gal4. Conversely, when two copies of a thymidine-rich element from a pol II enhancer were placed upstream of a pol I promoter, transcription was stimulated 38-fold. This functional reciprocity of pol I and II enhancers may reflect similarities in the mechanisms of transcriptional activation. The pol I enhancer also contains an element that appears to be pol I-specific and prevent the activation of pol II. PMID- 2236034 TI - Beta-globin locus activation regions: conservation of organization, structure, and function. AB - The human beta-globin locus activation region (LAR) comprises four erythroid specific DNase I hypersensitive sites (I-IV) thought to be largely responsible for activating the beta-globin domain and facilitating high-level erythroid specific globin gene expression. We identified the goat beta-globin LAR, determined 10.2 kilobases of its sequence, and demonstrated its function in transgenic mice. The human and goat LARs share 6.5 kilobases of homologous sequences that are as highly conserved as the epsilon-globin gene promoters. Furthermore, the overall spatial organization of the two LARs has been conserved. These results suggest that the functionally relevant regions of the LAR are large and that in addition to their primary structure, the spatial relationship of the conserved elements is important for LAR function. PMID- 2236035 TI - Chlamydomonas telomere sequences are A+T-rich but contain three consecutive G-C base pairs. AB - We have isolated telomeric DNA and telomere-associated sequences from Chlamydomonas reinhardtii. The terminal telomere sequences of the green alga Chlamydomonas are composed of (TTTTAGGG)n repeats that are similar, but not identical, to those of the higher plant Arabidopsis thaliana. We demonstrate that these repeats are telomeric by their preferential sensitivity to nuclease Bal-31 digestion, their similarity to A. thaliana telomeres, their orientation relative to the end of the chromosome, and the methods used for their isolation. Five independent telomere clones were isolated, and three of these clones include closely related telomere-associated sequences. One of these telomere-associated sequences hybridizes to a number of genomic fragments sensitive to digestion with the exonuclease Bal-31. Like telomere sequences from other organisms, the C. reinhardtii telomeres display a bias for guanine and thymine nucleotides on the 3'-end strand. However, the sequence of Chlamydomonas telomeres is more A + T rich than any other known telomere sequence. We propose that the common feature of all known telomere is the frequent occurrence of tracts of three or more adjacent guanine residues. PMID- 2236036 TI - Amplification of large artificial chromosomes. AB - Yeast artificial chromosome cloning is an attractive technology for genomic mapping studies because very large DNA segments can be readily propagated. However, detailed analyses often require the extensive application of blotting hybridization techniques because artificial chromosomes are normally present at only one copy per haploid genome. We have developed a cloning vector and host strain that alleviate this problem by permitting copy number amplification of artificial chromosomes. The vector includes a conditional centromere that can be turned on or off by changing the carbon source. Strong selective pressure for extra copies of the artificial chromosome can be applied by selecting for the expression of a heterologous thymidine kinase gene. When this system was used, artificial chromosomes ranging from about 100 to 600 kilobases in size were readily amplified 10- to 20-fold. The selective conditions did not induce obvious rearrangements in any of the clones tested. Reactivation of the centromere in amplified artificial chromosome clones resulted in stable maintenance of an elevated copy number for 20 generations. Applications of copy number control to various aspects of artificial chromosome analysis are addressed. PMID- 2236037 TI - Electrophoretic karyotype for Dictyostelium discoideum. AB - This paper reports on the separation of the Dictyostelium discoideum chromosomes by pulse-field electrophoresis and the correlation of the electrophoretic pattern with linkage groups established by classical genetic methods. In two commonly used laboratory strains, five chromosome-sized DNA molecules have been identified. Although the majority of the molecular probes used in this study can be unambiguously assigned to established linkage groups, the electrophoretic karyotype differs between the closely related strains AX3k and NC4, suggesting that chromosomal fragmentation may have occurred during their maintenance and growth. The largest chromosome identified in this study is approximately 9 million base pairs. To achieve resolution with molecules of this size, programmed voltage gradients were used in addition to programmed pulse times. PMID- 2236038 TI - Polymerase chain reaction-aided genomic sequencing of an X chromosome-linked CpG island: methylation patterns suggest clonal inheritance, CpG site autonomy, and an explanation of activity state stability. AB - The 5' region of the gene encoding human X chromosome-linked phosphoglycerate kinase 1 (PGK1) is a promoter-containing CpG island known to be methylated at 119 of 121 CpG dinucleotides in a 450-base-pair region on the inactive human X chromosome in the hamster-human cell line X8-6T2. Here we report the use of polymerase chain reaction-aided genomic sequencing to determine the complete methylation pattern of this region in clones derived from X8-6T2 cells after treatment with the methylation inhibitor 5-azacytidine. We find (i) a clone showing full expression of human phosphoglycerate kinase is fully unmethylated in this region; (ii) clones not expressing human phosphoglycerate kinase remain methylated at approximately 50% of CpG sites, with a pattern of interspersed methylated (M) and unmethylated (U) sites different for each clone; (iii) singles, defined as M-U-M or U-M-U, are common; and (iv) a few CpG sites are partially methylated. The data are interpreted according to a model of multiple, autonomous CpG sites, and estimates are made for two key parameters, maintenance efficiency (Em approximately 99.9% per site per generation) and de novo methylation efficiency (Ed approximately 5%). These parameter values and the hypothesis that several independent sites must be unmethylated for transcription can explain the stable maintenance of X chromosome inactivation. We also consider how the active region is kept free of methylation and suggest that transcription inhibits methylation by decreasing Em so that methylation cannot be maintained. Thus, multiple CpG sites, independent with respect to a dynamic methylation system, can stabilize two alternative states of methylation and transcription. PMID- 2236039 TI - A putative protein kinase gene (kin1+) is important for growth polarity in Schizosaccharomyces pombe. AB - Mixed synthetic oligonucleotides encoding a sequence conserved among tyrosine specific protein kinases were used to probe the genome of the fission yeast Schizosaccharomyces pombe. A single gene (kin1+) was isolated that encodes a putative protein kinase closely related to the KIN1- and KIN2-encoded serine/threonine-specific protein kinases of Saccharomyces cerevisiae. kin1+ is transcribed into a 3.5-kilobase mRNA that contains an uninterrupted open reading frame encoding a polypeptide of 98 kDa. In contrast to results obtained with kin mutants of S. cerevisiae, disruption of the Sc. pombe kin1+ gene resulted in recessive morphological and growth defects. kin1-disrupted cells grew slowly on enriched medium and grew as spheres, in contrast to wild-type Sc. pombe cells, which grow as rods. Relative to kin1+ cells, kin1-disrupted cells were differentially sensitive to lysis by treatment with alpha- and beta-glucanases, suggesting an alteration in either the composition or the organization of their cell walls. PMID- 2236040 TI - Size polymorphism of chicken major histocompatibility complex-encoded B-G molecules is due to length variation in the cytoplasmic heptad repeat region. AB - B-G antigens are cell-surface molecules encoded by a highly polymorphic multigene family located in the chicken major histocompatibility complex (MHC). Rabbit antisera to B-G molecules immunoprecipitate 3-6 bands from iodinated erythrocytes by sodium dodecyl sulfate (SDS) gels under reducing conditions. These are all B-G molecules because they all map to the B-G region of the chicken MHC in congenic and recombinant chickens, most are directly recognized by the antisera, most form disulfide-linked dimers, and none bear N-linked carbohydrate. Both apparent homodimers and heterodimers are found, which bear intrachain disulfide bonds. All 3-6 bands have different mobilities in SDS gels between different haplotypes, ranging from 30 to 55 kDa. This size polymorphism is not affected by glycosidase treatment or addition of protease inhibitors. Partial proteolysis of cell surface iodinated B-G molecules generates extremely similar patterns of spots, both within and between haplotypes. These surface-iodinated peptides bear either interchain or intrachain disulfide bonds. Additional peptides are generated by proteolysis of B-G molecules iodinated after isolation. Thus, it appears that the extracellular regions of these molecules are very similar and that the length polymorphism is due to variations in the cytoplasmic regions. Inspection of the cDNA-derived protein sequence in this region shows many heptad repeats, which may allow variation in length by step deletion and alternative splicing. The repeats indicate an alpha-helical coiled-coil structure, which could form an interaction between subunits of the dimer or with the cytoskeleton or both. PMID- 2236041 TI - The recombinant immunotoxin anti-Tac(Fv)-Pseudomonas exotoxin 40 is cytotoxic toward peripheral blood malignant cells from patients with adult T-cell leukemia. AB - Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin containing the heavy and light variable regions of the anti-Tac monoclonal antibody fused to a mutant form of Pseudomonas exotoxin (PE). Anti-Tac binds to the p55 subunit of the human interleukin 2 (IL-2) receptor, and anti-Tac(Fv)-PE40 kills human or monkey cell lines that contain either the intact IL-2 receptor or its p55 subunit alone. To assess the usefulness of anti-Tac(Fv)-PE40 in treatment of IL-2 receptor-positive leukemia, we tested peripheral blood mononuclear cells from six patients with adult T-cell leukemia. In each of the six patients, anti-Tac(Fv)-PE40 was extremely cytotoxic to the malignant cells. Metabolic activity and sensitivity of the fresh cells improved when a small amount of IL-2 (10 units per ml) was present during incubation. The toxin concentration necessary to inhibit protein synthesis by 50% after 16-hr incubation of cells with immunotoxin varied from 1.6 to 16 ng/ml (2.5-25 x 10(-11) M). In every case, binding was by means of the Tac antigen because anti-Tac(Fv)-PE40 cytotoxicity was prevented by adding excess anti-Tac antibody. Moreover, anti-Tac alone or an inactive mutant of anti-Tac(Fv) PE40 without ADP-ribosylation activity had very little cytotoxic activity. Peripheral blood mononuclear cells from normal controls, from a patient with Tac negative leukemia, and from adult T-cell leukemia patients without significant peripheral blood involvement were not sensitive to anti-Tac(Fv)-PE40. These results indicate that anti-Tac(Fv)-PE40 is a potent cytotoxin against adult T cell leukemia cells in vitro and warrants clinical testing. PMID- 2236042 TI - Downstream secondary structure facilitates recognition of initiator codons by eukaryotic ribosomes. AB - Recognition of an AUG initiator codon in a suboptimal context improves when a modest amount of secondary structure is introduced near the beginning of the protein-coding sequence. This facilitating effect depends on the position of the downstream stem-loop (hairpin) structure. The strongest facilitation is seen when the hairpin is separated from the preceding AUG codon by 14 nucleotides. Because 14 nucleotides corresponds to the approximate distance between the leading edge of the ribosome and its AUG-recognition center as measured by ribonuclease protection experiments, a likely explanation for the enhancing effect of a downstream hairpin is that secondary structure slows scanning, thereby providing more time for recognition of the AUG codon, and the facilitation is greatest when the 40S ribosome stalls with its AUG-recognition center directly over the AUG. The variable ability of mammalian ribosomes to initiate at non-AUG codons in vitro is also explicable by the presence or absence of a stem-loop structure just downstream from the alternative initiator codon. This may be relevant to recent reports of adventitious upstream initiation events at non-AUG codons in some vertebrate mRNAs that have structure-prone, G + C-rich leader sequences. PMID- 2236043 TI - Fructose-induced aberration of metabolism in familial gout identified by 31P magnetic resonance spectroscopy. AB - The hyperuricemia responsible for the development of gouty arthritis results from a wide range of environmental factors and underlying genetically determined aberrations of metabolism. 31P magnetic resonance spectroscopy studies of children with hereditary fructose intolerance revealed a readily detectable rise in phosphomonoesters with a marked fall in inorganic phosphate in their liver in vivo and a rise in serum urate in response to very low doses of oral fructose. Parents and some family members heterozygous for this enzyme deficiency showed a similar pattern when given a substantially larger dose of fructose. Three of the nine heterozygotes thus identified also had clinical gout, suggesting the possibility of this defect being a fairly common cause of gout. In the present study this same noninvasive technology was used to identify the same spectral pattern in 2 of the 11 families studied with hereditary gout. In one family, the index patient's three brothers and his mother all showed the fructose-induced abnormality of metabolism, in agreement with the maternal inheritance of the gout in this family group. The test dose of fructose used produced a significantly larger increment in the concentration of serum urate in the patients showing the changes in 31P magnetic resonance spectra than in the other patients with familial gout or in nonaffected members, thus suggesting a simpler method for initial screening for the defect. PMID- 2236044 TI - Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells. AB - Transplantation of bone marrow cells from nonobese diabetic (NOD) mice, a model for type 1 diabetes mellitus, to C3H/HeN mice, which express I-E alpha molecules and have aspartic acid at residue 57 of the I-A beta chain, induced insulitis followed by overt diabetes in the recipient C3H/HeN mice more than 40 weeks after bone marrow transplantation. When cyclosporin A, which perturbs T-cell functions, was injected intraperitoneally into [NOD----C3H/HeN] chimeric mice daily for 1 month, the chimeric mice developed insulitis and overt diabetes within 20 weeks following bone marrow transplantation. Transplantation of bone marrow cells from (NZW x BXSB)F1 mice, which develop lupus nephritis, myocardial infarction, and idiopathic thrombocytopenic purpura, into C3H/HeN or C57BL/6J mice induced in the recipient strains both lupus nephritis and idiopathic thrombocytopenic purpura more than 3 months after transplantation. Transplantation of a stem-cell-enriched population from (NZW x BXSB)F1 mice into normal mice also induced autoimmune disease in the recipients. These results indicate that both systemic autoimmune disease and organ-specific autoimmune disease originate from defects that reside within the stem cells; the thymus and environmental factors such as sex hormones appear to act only as accelerating factors. PMID- 2236045 TI - A principle for the formation of the spatial structure of cortical feature maps. AB - Orientation-selective cells in the striate cortex of higher animals are organized as a hierarchical topographic map of two stimulus features: (i) position in visual space and (ii) orientation. We show that the observed structure of the topographic map can arise from a principle of continuous mapping. For the realization of this principle we use a mathematical model that can be interpreted as an adaptive process changing a set of synaptic weights, or synaptic connection strengths, between two layers of cells. The patterns of orientation preference and selectivity generated by the model are similar to the patterns seen in the visual cortex of macaque monkey and cat and correspond to a neural projection that maps a more than two-dimensional feature space onto a two-dimensional cortical surface under the constraint that shape and position of the receptive fields of the neurons very smoothly over the cortical surface. PMID- 2236047 TI - Molecular cloning and characterization of the immunologically protective surface glycoprotein GP46/M-2 of Leishmania amazonensis. AB - Immunization of mice with the GP46/M-2 membrane glycoprotein has been demonstrated to elicit protection against infection with the parasitic protozoan Leishmania amazonensis. As this molecule is important for future vaccine studies of leishmaniasis, the gene encoding the GP46/M-2 surface membrane glycoprotein of Leishmania amazonensis has been cloned and sequenced. The protein sequence derived from the DNA sequence data is consistent with the known biochemical and immunochemical properties of the protein and indicates a number of structural areas of interest. A repetitive sequence (24 amino acids repeated four times) occurs within the amino-terminal portion of the molecule and constitutes approximately 22% of the total mature protein. The protease-resistant immunodominant carboxyl-terminal domain of the protein comprises approximately half of the molecule and consists of proline-rich and cysteine-rich areas of sequence; the distribution of cysteine residues is suggestive of metal binding motifs. The sequence predicts a hydrophobic leader peptide, and a putative attachment site for a glycosyl-phosphatidylinositol anchor is indicated at the carboxyl terminus, consistent with the membrane location of the protein. Southern blot analyses also indicate the presence of a GP46/M-2 gene family. PMID- 2236049 TI - Odor types determined by the major histocompatibility complex in germfree mice. AB - The major histocompatibility complex (MHC) is the prime but not exclusive determinant of genetically specific constitutive body odors, termed odor types, represented strongly in urine of the mouse. Perception of MHC-determined odor types influences reproductive behavior in the contexts of mate choice and maintenance of early pregnancy, tending to favor the propagation of one MHC type over another. How MHC genotype determines MHC odor type is unknown. One possible explanation is that differential odorants are generated by populations of commensal microorganisms whose composition is somehow geared to MHC diversity. This hypothesis was tested in the Y-maze system in which mice are trained to distinguish the urinary odors of MHC-congenic mice. First, it was shown that mice could readily be trained to distinguish the urines of germfree MHC-congenic mice. Second, it was shown that mice trained to distinguish the urines of conventionally maintained MHC-congenic mice could as readily distinguish the urines of germfree MHC-congenic mice. These results imply that MHC-determined odor types do not depend on odorants generated by microorganisms. PMID- 2236048 TI - Renaturation of complementary DNA strands mediated by purified mammalian heterogeneous nuclear ribonucleoprotein A1 protein: implications for a mechanism for rapid molecular assembly. AB - Purified heterogeneous nuclear ribonucleoprotein (hnRNP) A1 protein, which is found in vivo associated with heterogeneous nuclear RNA (hnRNA), promotes the rapid renaturation of nucleic acid strands. Maximal renaturation activity requires the glycine-rich carboxyl-terminal one-third of the protein, although the amino-terminal two-thirds also has activity. The A1-mediated reaction is second-order with respect to complementary DNA concentration, and the renaturation rate constant at 37 degrees C with A1 is about 3000-fold greater than in the absence of the protein. At 60 degrees C, the A1-mediated renaturation rate is even faster, and is about 300-fold greater than protein-free reactions carried out at 68 degrees C in 1 M NaCl. Provided that sufficient A1 protein is present to coat all strands in solution, the presence of nonhomologous, single stranded DNA does not significantly inhibit the reaction. Moreover, renaturation of short strands to their complement contained in very long strands is nearly as efficient as between two short strands. These results indicate that A1 may be useful for procedures that rely on nucleic acid renaturation. We propose that A1 promotes rapid renaturation primarily by reducing the entropic barrier of bimolecular strand association through relatively transient interactions between A1-coated strands. Such interactions, mediated by flexible repeating domains, may act generally to increase the association kinetics of highly specific molecular assemblies in processes such as RNA maturation, transcription, translation, and transport. PMID- 2236046 TI - Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus. AB - Fanconi anemia (FA) is an inherited human disorder associated with a predisposition to cancer and characterized by anomalies in the processing of DNA cross-links and certain monoadducts. We reported previously that the frequency of psoralen-photoinduced mutations at the HPRT locus is lower in FA cells than in normal cells. This hypomutability is shown here to be associated with an increased frequency of deletions in the HPRT gene when either a mixture of cross links and monoadducts or monoadducts alone are induced. Molecular analysis of mutants in the HPRT gene was carried out. In normal cells the majority of spontaneous and induced mutants are point mutations whereas in FA deletion mutations predominate. In that case a majority of mutants were found to lack individual exons or small clusters of exons whereas in normal cells large (complete or major gene loss) and small deletions are almost equally represented. Thus we propose that the FA defect lies in a mutagenic pathway that, in normal cells, involves bypassing lesions and subsequent gap filling by a recombinational process during replication. PMID- 2236050 TI - Autogenous suppression of an opal mutation in the gene encoding peptide chain release factor 2. AB - The peptide chain release factor 2 (RF2) gene, prfB, was cloned from Salmonella typhimurium by DNA hybridization using the Escherichia coli prfB probe. The nucleotide and amino acid sequences of prfB are 87.0% and 95.6% homologous between E. coli and S. typhimurium, respectively, including an in-frame premature UGA stop codon at position 26, the site of +1 frameshift for mature RF2 synthesis. The supK584 mutation, which had been isolated as a recessive UGA suppressor in S. typhimurium, caused an opal (UGA) substitution at amino acid position 144 in the prfB gene. Complementation, reversion, and gene fusion analyses led to the conclusion that supK is a S. typhimurium RF2 mutation and this opal RF2 mutation generates a UGA suppressor activity, presumably because of inefficient translation termination due to the reduced cellular level of RF2. In fact, suppression of the supK opal mutation results from a form of autogenous control of RF2 synthesis. PMID- 2236051 TI - Temporary amelioration of hyperlipidemia in low density lipoprotein receptor deficient rabbits transplanted with genetically modified hepatocytes. AB - Familial hypercholesterolemia is an inherited disease in humans that is associated with coronary artery disease and is caused by a deficiency of the receptor that mediates the internalization of low density lipoprotein (LDL). We have used an animal model for familial hypercholesterolemia, the Watanabe heritable hyperlipidemic (WHHL) rabbit, to design a therapeutic approach for this disease, which attempts to correct the hepatic defect in LDL receptor expression. Hepatocytes were harvested from WHHL rabbits, plated in primary cultures, and exposed to recombinant retroviruses capable of efficiently transferring a functional human LDL receptor gene. Genetically modified cells were harvested and infused into the portal vein of WHHL recipients, who were analyzed for metabolic consequences of human LDL receptor expression. Each animal exhibited a statistically significant decrease in total serum cholesterol 2-6 days after transplantation, with an eventual return to pretreatment levels. Proviral DNA sequences and virus-directed transcripts were detected in liver tissue 24 hr after transplantation. In situ hybridization demonstrated provirus expression in a small population of hepatocytes distributed in periportal sections of the liver. This study illustrates the potential of somatic gene therapy in ameliorating hyperlipidemia associated with familial hypercholesterolemia. PMID- 2236052 TI - MyoD induces growth arrest independent of differentiation in normal and transformed cells. AB - MyoD is a gene involved in the control of muscle differentiation. We show that MyoD causes growth arrest when expressed in cell lines derived from tumors or transformed by different oncogenes. MyoD-induced growth inhibition was demonstrated by reduction in the efficiency of colony formation and at the single cell level. We further show that MyoD growth inhibition can occur in cells that are not induced to activate muscle differentiation markers. The inhibitory activity of MyoD was mapped to the same 68-amino acid segment necessary and sufficient for induction of muscle differentiation, the basic-helix-loop-helix motif. Mutants with alterations in the basic region of MyoD that fail to bind or do not activate a muscle-specific enhancer inhibited growth; mutants with deletions in the helix-loop-helix region failed to inhibit growth. Thus, inhibition of cell growth by MyoD seems to occur by means of a parallel pathway to the one that leads to myogenesis. We conclude that MyoD is a prototypic gene capable of functionally activating intracellular growth inhibitory pathways. PMID- 2236053 TI - Identification of mutations in regions corresponding to the two putative nucleotide (ATP)-binding folds of the cystic fibrosis gene. AB - Additional mutations in the cystic fibrosis (CF) gene were identified in the regions corresponding to the two putative nucleotide (ATP)-binding folds (NBFs) of the predicted polypeptide. The patient cohort included 46 Canadian CF families with well-characterized DNA marker haplotypes spanning the disease locus and several other families from Israel. Eleven mutations were found in the first NBF, 2 were found in the second NBF, but none was found in the R-domain. Seven of the mutations were of the missense type affecting some of the highly conserved amino acid residues in the first NBF; 3 were nonsense mutations; 2 would probably affect mRNA splicing; 2 corresponded to small deletions, including another 3-base pair deletion different from the major mutation (delta F508), which could account for 70% of the CF chromosomes in the population. Nine of these mutations accounted for 12 of the 31 non-delta F508 CF chromosomes in the Canadian families. The highly heterogeneous nature of the remaining CF mutations provides important insights into the structure and function of the protein, but it also suggests that DNA-based genetic screening for CF carrier status will not be straightforward. PMID- 2236055 TI - Cell position and developmental fate in leech embryogenesis. AB - The o and p blast cell bandlets of the leech Theromyzon rude, which normally produce two different sets of identifiable cells designated the "O" and "P" fates, respectively, form an equivalence group: in embryos experimentally deprived of their p bandlet, the blast cells of the adjacent o bandlet may "transfate" and take on the P fate. Loss of the p bandlet is not, however, a sufficient condition for transfating of the o bandlet. Rather, loss of the p bandlet allows the o bandlet to shift into ectopic positions, and it is the ultimate position of the o bandlet that mandates which fate--O or P--the blast cells will take on. Therefore, the choice of the pluripotent o blast cells to follow either the O or P developmental pathway depends on their perception of positional cues provided by cells outside the equivalence group rather than on a direct interaction with p blast cell equivalence group members. PMID- 2236054 TI - Role of tryptophan repeats and flanking amino acids in Myb-DNA interactions. AB - The c-myb protooncogene codes for a sequence-specific DNA-binding protein that appears to act as a transcriptional regulator and is highly conserved through evolution. The DNA-binding domain of Myb has been shown to contain three imperfectly conserved repeats of 52 amino acids that constitute the amino terminal end. Within each repeat, there are three tryptophans that are separated by 18 or 19 amino acids and are flanked by basic amino acids. To determine the role of tryptophans and the flanking basic amino acids in the DNA-binding activity of Myb proteins, we have selectively mutagenized individual tryptophans as well as some of the amino acid residues that flank these tryptophans. Replacement of these tryptophans with glycine, proline, or arginine abolished the DNA-binding activity whereas replacement with other aromatic amino acids or leucine or alanine did not appreciably affect this activity. On the other hand the replacement of two amino acids, asparagine and lysine, that flank the last tryptophan with acidic amino acids completely abolished their DNA-binding activity. These results are consistent with a model we present in which the tryptophans form a hydrophobic scaffold that plays a crucial role in maintaining the helix-turn-helix structure of the DNA binding domain. Basic and polar amino acids adjacent to these tryptophans seem to participate directly in DNA binding. PMID- 2236056 TI - Architecture of ribosomal RNA: constraints on the sequence of "tetra-loops". AB - The four-base loops that cap many double-helical structures in rRNA (the so called "tetra-loops") exhibit highly invariant to highly variable sequences depending upon their location in the molecule. However, in the vast majority of these cases the sequence of a tetra-loop is independent of its location and conforms to one of three general motifs, GNRA, UNCG, and (more rarely) CUUG. For the most frequently varying of the 16S rRNA tetra-loops, that at position 83 (Escherichia coli numbering), the three sequences CUUG, UUCG, and GCAA account for almost all examples encountered, and each of them has independently arisen at least a dozen times. The closing base pair of tetra-loop hairpins reflects the loop sequence, tending to be C.G for UUCG loops and G.C for CUUG loops. PMID- 2236057 TI - Free energy of sickling: A simulation analysis. AB - Molecular dynamics simulations were performed to calculate the difference between the dimerization free energies of normal human deoxyhemoglobin (HbA) and the mutant sickle-cell deoxyhemoglobin HbS (Glu-beta 6----Val) for one of the lateral contacts in the HbS x-ray structure. The simulations yield a value of--15 kcal/mol. Although there is no quantitative experimental value for comparison, this is in qualitative agreement with the experimental result that HbS self assembles into multistranded fibers that are responsible for erythrocyte sickling, while HbA does not. The free-energy difference was decomposed into enthalpic and entropic terms, both of which are significant, and the contributions of individual protein residues and of the solvent were examined. Electrostatic effects play the dominant role in favoring dimerization of HbS compared with HbA; van der Waals interactions make a negligible contribution to the difference. Both differential solvation and protein-protein interactions are important. Interactions within the donor tetramer (i.e., that containing the Glu beta 6 mutation site), as well as those with the acceptor tetramer, contribute to the preferential free energy of dimerization of HbS. PMID- 2236058 TI - Genetic diversity and ecogeographical differentiation among ribosomal DNA alleles in wild and cultivated barley. AB - DNA from 267 accessions of wild barley from ecologically diverse habitats in Israel and Iran and from 92 accessions of cultivated barley from throughout the world were assayed for the 20 ribosomal DNA (rDNA) spacer-length variants that have been identified in the barley species. These 20 spacer-length variants, which are detectable by Southern blot hybridization, serve as markers of rDNA alleles of two Mendelian loci, Rrn1 and Rrn2. All of the populations of wild barley studied were polymorphic for both loci. In wild barley allele 112 (Rrn1) and allele 107 (Rrn2) behaved as widely adapted wild-type alleles; in our sample of cultivated barley allele 112 also behaved as a wild-type allele but allele 104 was somewhat more frequent than allele 107 in Rrn2. A few other alleles were locally frequent in wild barley. However, most of the 20 alleles were infrequent or rare and such alleles were often associated as "hitchhikers" with one of the wild-type alleles in compound two-component alleles. Allelic and genotypic frequencies differed widely in different habitats in correlation with eight of nine factors of the physical environment. Discrete log-linear multivariate analyses revealed statistically significant associations among alleles of Rrn1 and Rrn2. It was concluded that natural selection acting differentially on various rDNA alleles plays a major role in the development and maintenance of observed patterns of molecular and genetic organization of rDNA variability. PMID- 2236059 TI - Molecular cloning and amino acid sequence of brain L-glutamate decarboxylase. AB - We used specific polyclonal antibodies against L-glutamate decarboxylase (GAD) to screen a mouse brain cDNA library that was constructed in the expression vector lambda gt11. We obtained 1.5 x 10(6) recombinant DNA clones in the mouse brain cDNA library. One of the clones was positively identified as a GAD clone on the basis of the following results: (i) the clone and its secondary and tertiary clones all reacted strongly with anti-GAD antibodies; (ii) the fusion protein obtained from lambda GAD-Y1089 showed good GAD enzyme activity as determined by both CO2 and gamma-aminobutyric acid methods. The GAD clone thus obtained contains GAD cDNA of approximately 2.6 kilobases that has one internal EcoRI site. After GAD cDNA was cut at the EcoRI site, two DNA fragments of about 1.6 and 1.0 kilobases were obtained at the 5' and 3' ends, respectively. The cDNA insert was found to be composed of 2632 base pairs, the translation initiation site was assigned to the methionine codon ATG, and the termination site was found to be TGA (positions 2216-2218). Furthermore, the coding region in 2169 base pairs was found to consist of 723 amino acids. The protein has a molecular weight of 83,207 and contains 83 strongly basic, 108 strongly acidic, 226 hydrophobic, and 221 polar amino acids with an isoelectric point of 5.355. The relationship of this GAD cDNA to other forms of GAD is discussed. PMID- 2236060 TI - Functional analysis of protein N-myristoylation: metabolic labeling studies using three oxygen-substituted analogs of myristic acid and cultured mammalian cells provide evidence for protein-sequence-specific incorporation and analog-specific redistribution. AB - Covalent attachment of myristic acid (C14:0) to the NH2-terminal glycine residue of a number of cellular, viral, and oncogene-encoded proteins is essential for full expression of their biological function. Substitution of oxygen for methylene groups in this fatty acid does not produce a significant change in chain length or stereochemistry but does result in a reduction in hydrophobicity. These heteroatom-containing analogs serve as alternative substrates for mammalian myristoyl-CoA:protein N-myristoyltransferase (EC 2.3.1.97) and offer the opportunity to explore structure/function relationships of myristate in N myristoyl proteins. We have synthesized three tritiated analogs of myristate with oxygen substituted for methylene groups at C6, C11, and C13. Metabolic labeling studies were performed with these compounds and (i) a murine myocyte cell line (BC3H1), (ii) a rat fibroblast cell that produces p60v-src (3Xsrc), or (iii) NIH 3T3 cells that have been engineered to express a fusion protein consisting of an 11-residue myristoylation signal from the Rasheed sarcoma virus (RaSV) gag protein linked to c-Ha-ras with a Cys----Ser-186 mutation. This latter mutation prevents isoprenylation and palmitoylation of ras. Two-dimensional gel electrophoresis of membrane and soluble fractions prepared from cell lysates revealed different patterns of incorporation of the analogs into cellular N myristoyl proteins (i.e., protein-sequence-specific incorporation). In addition, proteins were identified that underwent redistribution from membrane to soluble fractions after incorporating one but not another analog (analog-specific redistribution). Comparable studies using the model RaSV-ras chimeric protein also demonstrated analog-specific differences in incorporation, varying from approximately 25% of the total RaSV-ras chimeric protein with 5 octyloxypentanoate to greater than 50% with 12-methoxydodecanoate. Modification by this latter compound was so extensive that the amount of membrane-associated N myristoylated protein was decreased. Incorporation of each of the analogs caused a dramatic redistribution to the soluble fraction, comparable to that seen when myristoylation was completely blocked by mutating the protein's site of myristate attachment (glycine) to an alanine residue. The demonstration that these analogs differ in the extent to which they are incorporated and in their ability to cause redistribution of any single protein suggests that they may also have sufficient selectivity to be of potential therapeutic value. PMID- 2236061 TI - Cloning and sequence of the human adrenodoxin reductase gene. AB - Adrenodoxin reductase (ferrodoxin:NADP+ oxidoreductase, EC 1.18.1.2) is a flavoprotein mediating electron transport to all mitochondrial forms of cytochrome P450. We cloned the human adrenodoxin reductase gene and characterized it by restriction endonuclease mapping and DNA sequencing. The entire gene is approximately 12 kilobases long and consists of 12 exons. The first exon encodes the first 26 of the 32 amino acids of the signal peptide, and the second exon encodes the remainder of signal peptide and the apparent FAD binding site. The remaining 10 exons are clustered in a region of only 4.3 kilobases, separated from the first two exons by a large intron of about 5.6 kilobases. Two forms of human adrenodoxin reductase mRNA, differing by the presence or absence of 18 bases in the middle of the sequence, arise from alternate splicing at the 5' end of exon 7. This alternately spliced region is directly adjacent to the NADPH binding site, which is entirely contained in exon 6. The immediate 5' flanking region lacks TATA and CAAT boxes; however, this region is rich in G + C and contains six copies of the sequence GGGCGGG, resembling promoter sequences of "housekeeping" genes. RNase protection experiments show that transcription is initiated from multiple sites in the 5' flanking region, located about 21-91 base pairs upstream from the AUG translational initiation codon. PMID- 2236062 TI - Expression of fully functional tetrameric human hemoglobin in Escherichia coli. AB - Synthetic genes encoding the human alpha- and beta-globin polypeptides have been expressed from a single operon in Escherichia coli. The alpha- and beta-globin polypeptides associate into soluble tetramers, incorporate heme, and accumulate to greater than 5% of the total cellular protein. Purified recombinant hemoglobin has the correct stoichiometry of alpha- and beta-globin chains and contains a full complement of heme. Each globin chain also contains an additional methionine as an extension to the amino terminus. The recombinant hemoglobin has a C4 reversed-phase HPLC profile essentially identical to that of human hemoglobin A0 and comigrates with hemoglobin A0 on SDS/PAGE. The visible spectrum and oxygen affinity are similar to that of native human hemoglobin A0. The recombinant protein shows a reduction in Bohr and phosphate effects, which may be attributed to the presence of methionine at the amino termini of the alpha and beta chains. We have also expressed the alpha- and beta-globin genes separately and found that the expression of the alpha-globin gene alone results in a marked decrease in the accumulation of alpha-globin in the cell. Separate expression of the beta-globin gene results in high levels of insoluble beta-globin. These observations suggest that the presence of alpha- and beta-globin in the same cell stabilizes alpha globin and aids the correct folding of beta-globin. This system provides a simple method for expressing large quantities of recombinant hemoglobin and allows facile manipulation of the genes encoding hemoglobin to produce functionally altered forms of this protein. PMID- 2236063 TI - Rapid, nonradioactive detection of clonal T-cell receptor gene rearrangements in lymphoid neoplasms. AB - Southern blot hybridization analysis of clonal antigen receptor gene rearrangements has proved to be a valuable adjunct to conventional methods for diagnosing lymphoid neoplasia. However, Southern blot analysis suffers from a number of technical disadvantages, including the time necessary to obtain results, the use of radioactivity, and the susceptibility of the method to various artifacts. We have investigated an alternative approach for assessing the clonality of antigen receptor gene rearrangements in lymphoid tissue biopsy specimens. This approach involves the amplification of rearranged gamma T-cell receptor genes by the polymerase chain reaction and analysis of the polymerase chain reaction products by denaturing gradient gel electrophoresis. By use of this approach, clonal rearrangements from neoplastic lymphocytes constituting as little as 0.1-1% of the total cells in the tissue are detected as discrete bands in the denaturing gel after the gel is stained with ethidium bromide and viewed under ultraviolet light. In contrast, polyclonal rearrangements from reactive lymphocytes appear as a diffuse smear along the length of the gel. Our findings suggest that polymerase chain reaction combined with denaturing gradient gel electrophoresis may offer a rapid, nonradioactive, and sensitive alternative to Southern blot analysis for the diagnostic evaluation of lymphoid tissue biopsy specimens. PMID- 2236064 TI - Molecular structure of a major insulin/mitogen-activated 70-kDa S6 protein kinase. AB - The molecular structure of a rat hepatoma 70-kDa insulin/mitogen-stimulated S6 protein kinase, obtained by molecular cloning, is compared to that of a rat homolog of the 85-kDa Xenopus S6 protein kinase alpha; both kinases were cloned from H4 hepatoma cDNA libraries. The 70-kDa S6 kinase (calculated molecular mass of 59,186 Da) exhibits a single catalytic domain that is most closely related in amino acid sequence (56% identity) to the amino-terminal, kinase C-like domain of the rat p85 S6 kinase (calculated molecular mass of 82,695 Da); strong similarity extends through a further 67 residues carboxyl-terminal to the catalytic domain (40% identity), corresponding to a region also conserved among the kinase C family. Outside of this segment of approximately 330 amino acids, the structures of the p70 and p85 S6 kinases diverge substantially. The p70 S6 kinase is known to be activated through serine/threonine phosphorylation by unidentified insulin/mitogen-activated protein kinases. A model for the regulation of p70 S6 protein kinase activity is proposed wherein the low activity of the unphosphorylated enzyme results from the binding of a basic, inhibitory pseudosubstrate site (located carboxyl-terminal to the extended catalytic domain) to an acidic substrate binding region (located amino-terminal to the catalytic domain); substrate binding is thereby prevented. S6 kinase activation requires displacement of this inhibitory segment, which is proposed to occur consequent to its multiple phosphorylation. The putative autoinhibitory segment contains several serine and threonine residues, each followed directly by a proline residue. This motif may prevent autophosphorylation but permit transphosphorylation; two of these serine residues reside in a maturation promoting factor (MPF)/cdc-2 consensus motif. Thus, hormonal regulation of S6 kinase may involve the action of MPF/cdc-2 or protein kinases with related substrate specificity. PMID- 2236065 TI - ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains. AB - Interferon-stimulated gene factor 3 (ISGF3) is the ligand-dependent transcriptional activator that, in response to interferon treatment, is assembled in the cell cytoplasm, is translocated to the nucleus, and binds the consensus DNA site, the interferon-stimulated response element. We have purified ISGF3 and identified its constituent proteins: a DNA-binding protein of 48 kDa and three larger polypeptides (84, 91, and 113 kDa), which themselves do not have DNA binding activity. The multisubunit structure of ISGF3 most likely reflects its participation in receiving a ligand-dependent signal, translocating to the nucleus, and binding to DNA to activate transcription. PMID- 2236066 TI - Initiation of rolling-circle replication in pT181 plasmid: initiator protein enhances cruciform extrusion at the origin. AB - Plasmid pT181 DNA secondary structures have been analyzed in vitro by nuclease S1 digestion and in vivo by bromoacetaldehyde treatment. A cruciform structure occurring at the pT181 replication origin in vitro is greatly enhanced by the binding of the plasmid-encoded initiator protein RepC. In vivo a DNA secondary structure also existed in the replication origin. Its frequency of formation was correlated with efficiency of RepC utilization. These data suggest that cruciform extrusion at the origin is involved in initiation of pT181 rolling-circle replication. A neighboring DNA structure influences the conformation of the origin in vivo. PMID- 2236067 TI - Imaging cytoskeleton--mitochondrial membrane attachments by embedment-free electron microscopy of saponin-extracted cells. AB - Embedment-free electron microscopy images the cytoskeleton and nuclear matrix, which are very difficult to visualize in conventional electron micrographs. However, to be effective, cell structures must be depleted of soluble proteins, which otherwise shroud cell architecture. Nonionic detergents effect this extraction, releasing soluble proteins but also destroying all membranes. Saponin can permeabilize plasma membranes, releasing soluble proteins while preserving many cytoplasmic membranes. Stereoscopic electron microscopy of resinless sections shows the many connections of the cytoskeleton to mitochondrial membranes. PMID- 2236068 TI - Volume-sensitive K-Cl cotransport in inside-out vesicles made from erythrocyte membranes from sheep of low-K phenotype. AB - Unidirectional K ion effluxes were measured from inside-out vesicles prepared from erythrocyte membranes from sheep of the low-K phenotype. Total K efflux was 150 nmol per mg of protein per hr in a Cl medium of 295 mosmol/kg (with the Na/K pump inhibited). Cl-dependent K efflux (determined with methanesulfonate replacing Cl) was 54 nmol/(mg.hr). Cl-dependent K efflux (K-Cl cotransport) increased to 77 nmol/(mg.hr) with osmotic swelling of approximately 30% in 230 mosmol/kg medium and decreased to 13 nmol/(mg.hr) after shrinkage of approximately 60% in 430-mosmol/kg medium. Osmotically induced changes in transport and vesicle volume were reversible. K-Cl cotransport was enhanced by ATP. Nonhydrolyzable ATP analogues failed to substitute for ATP, indicating that phosphorylation is involved. However, in the absence of added ATP there was significant K-Cl cotransport, suggesting that phosphorylation is not essential for function. The results provide clues about the nature of the signals detected by the sensor of cell volume changes and demonstrate that inside-out vesicles from sheep erythrocyte membranes provide an advantageous experimental system for investigation of the volume sensor. PMID- 2236069 TI - Duration of phasic electrical activity of the hypothalamic gonadotropin-releasing hormone pulse generator and dynamics of luteinizing hormone pulses in the rhesus monkey. AB - The secretion of luteinizing hormone (LH) by the pituitary gland is a pulsatile phenomenon. In the rhesus monkey, each pulse of LH in the peripheral circulation is associated with a characteristic increase in multiunit electrical activity (MUA) recorded from the medial basal hypothalamus. These "volleys" of electrical activity initiate the release of gonadotropin-releasing hormone (GnRH) into the pituitary portal circulation from the terminals of neurosecretory cells. Their duration varies from 1-3 min in normal, adult intact females to 10-25 min in long term ovariectomized monkeys. A variety of pharmacological interventions also modify volley duration. The purpose of this investigation was to determine the physiological significance of alterations in volley duration. The dynamics of LH pulses in ovariectomized animals were observed in a number of experimental circumstances in which MUA volley duration was reduced from a maximum of 23 min to a minimum of 4 min without significantly altering their frequency. The magnitude of each LH pulse was assessed by calculating the area under the curve delineated by the time course of LH above baseline. In eight experiments, a linear regression of these values on volley duration failed to reveal a significant correlation between MUA volley duration and the magnitude of LH pulses. These results suggest that all of the GnRH secreted per pulse is released at the onset of each MUA volley, the remainder of the increase in electrical activity having no further action on GnRH secretion, although effects on other systems cannot be excluded. PMID- 2236070 TI - Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. AB - The epidermal growth factor receptor gene has been found to be amplified and rearranged in human glioblastomas in vivo. Here we present the sequence across a splice junction of aberrant epidermal growth factor receptor transcripts derived from corresponding and uniquely rearranged genes that are coamplified and coexpressed with non-rearranged epidermal growth factor receptor genes in six primary human glioblastomas. Each of these six tumors contains aberrant transcripts derived from identical splicing of exon 1 to exon 8 as a consequence of a deletion-rearrangement of the amplified gene, the extent of which is variable among these tumors. In spite of this intertumoral variability, each intragenic rearrangement results in loss of the same 801 coding bases (exons 2-7) and creation of a new codon at the novel splice site in their corresponding transcripts. These rearrangements do not, however, affect the mRNA sequence for the signal peptide, the first five codons, or the reading frame downstream of the rearrangement. PMID- 2236071 TI - The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: cultured endothelial cells recycle L citrulline to L-arginine. AB - We have investigated the mechanism by which cultured endothelial cells generate L arginine (L-Arg), the substrate for the biosynthesis of endothelium-derived relaxing factor. When Arg-depleted endothelial cells were incubated in Krebs' solution for 60 min, L-Arg levels were significantly (9.7-fold) elevated. The generation of L-Arg coincided with a substantial decrease (90%) in intracellular L-glutamine (L-Gln), whereas all other amino acids were virtually unaffected. Changes in calcium, pH, or oxygen tension had no effect on L-Arg generation, which was, however, prevented when the cells were incubated in culture medium containing L-Gln. L-Arg generated by endothelial cells labeled with L-[14C]Arg was derived from an unlabeled intracellular source, for the specific activity of the intracellular L-Arg pool decreased substantially (8.8-fold) over 60 min. Arg depleted endothelial cells did not form urea or metabolize L-ornithine but converted L-citrulline (L-Cit) to L-Arg possibly via formation of L argininosuccinic acid. Nondepleted cells stimulated with the calcium ionophore A23187 showed only a transient accumulation of L-Cit, indicating that L-Cit is recycled to L-Arg during the biosynthesis of endothelium-derived relaxing factor. The generation of L-Arg by Arg-depleted endothelial cells was partially (45%) blocked by protease inhibitors, and various Arg-containing dipeptides were rapidly cleaved to yield L-Arg. Thus, cultured endothelial cells recycle L-Cit to L-Arg and possibly liberate peptidyl L-Arg. The Arg-Cit cycle appears to be the equivalent in the endothelial cell to the formation of urea by the liver. The biosynthesis of endothelium-derived relaxing factor may, therefore, not only produce a powerful vasodilator but also relieve the endothelial cell of excess nitrogen. PMID- 2236072 TI - A 47-kDa human nuclear protein recognized by antikinetochore autoimmune sera is homologous with the protein encoded by RCC1, a gene implicated in onset of chromosome condensation. AB - Several autoimmune sera from patients with Raynaud phenomenon decorated mammalian kinetochores and bound to a 47-kDa protein on immunoblots of nuclear lysates. Antibody affinity-purified from immunoblots of the 47-kDa band recognized kinetochores, but due to crossreaction with an 18-kDa protein, localization remains elusive. We used one of these sera to purify the antigen from HeLa cells synchronized in mitosis as a noncovalent complex with a 25-kDa protein. The antigen was released from DNA by intercalation with 25 mM chloroquine. Ion exchange chromatography yielded the pure complex with an apparent molecular size of 68 kDa, which was separated into its components by gel filtration in 6 M guanidinium chloride. Upon two-dimensional gel electrophoresis the 47-kDa protein gave two main spots of pI 6.6 and 6.7, respectively. Posttranslational modification is indicated by additional antigenic spots, by lack of a free alpha amino group, and by chromatographic behavior of peptides on reversed-phase chromatography. The amino acid sequence for 205 residues of the 47-kDa protein has been established. This sequence is highly homologous with the translated reading frame of RCC1, a gene reportedly involved in regulating onset of mammalian chromosome condensation. PMID- 2236073 TI - Src homology region 2 domains direct protein-protein interactions in signal transduction. AB - Cytoplasmic proteins that regulate signal transduction or induce cellular transformation, including cytoplasmic protein-tyrosine kinases, p21ras GTPase activating protein (GAP), phospholipase C gamma, and the v-crk oncoprotein, possess one or two copies of a conserved noncatalytic domain, Src homology region 2 (SH2). Here we provide direct evidence that SH2 domains can mediate the interactions of these diverse signaling proteins with a related set of phosphotyrosine ligands, including the epidermal growth factor (EGF) receptor. In src-transformed cells GAP forms heteromeric complexes, notably with a highly tyrosine phosphorylated 62-kDa protein (p62). The stable association between GAP and p62 can be specifically reconstituted in vitro by using a bacterial polypeptide containing only the N-terminal GAP SH2 domain. The efficient phosphorylation of p62 by the v-Src or v-Fps tyrosine kinases depends, in turn, on their SH2 domains and correlates with their transforming activity. In lysates of EGF-stimulated cells, the N-terminal GAP SH2 domain binds to both the EGF receptor and p62. Fusion proteins containing GAP or v-Crk SH2 domains complex with similar phosphotyrosine proteins from src-transformed or EGF-stimulated cells but with different efficiencies. SH2 sequences, therefore, form autonomous domains that direct signaling proteins, such as GAP, to bind specific phosphotyrosine-containing polypeptides. By promoting the formation of these complexes, SH2 domains are ideally suited to regulate the activation of intracellular signaling pathways by growth factors. PMID- 2236075 TI - Streamlined approach to creating yeast artificial chromosome libraries from specialized cell sources. AB - The study of tumor-specific chromosomal abnormalities has been severely impeded by an inability to link cytogenetic to molecular data. Restriction fragment length polymorphism mapping of any particular chromosomal rearrangement to the resolution limit of genetic methodology generates sets of probes that frequently are still too widely spaced to render the rearrangement breakpoints accessible to molecular isolation. The stable propagation of genomic fragments of up to one million base pairs in size as yeast artificial chromosomes (YACs) represents an important development in this regard. However, existing YAC libraries have been made from karyotypically normal sources making the localization and cloning of specific rearrangement breakpoints much more difficult. As a solution to this problem, we present an improved method for creating YAC libraries that can utilize specialized tumor-derived materials and that can be executed effectively in a small laboratory setting. Procedures that enabled more consistent DNA insert size selection and enhanced yeast transformation frequency were employed to generate a human YAC library from a neuroepithelioma cell line containing a characteristic t(11;22) chromosomal translocation. Approximately 40,000 colonies with an average insert size of 330 kilobase pairs were created. This library was screened with two single-copy probes that bracket the translocation breakpoint. YAC clones ranging from 370 to 550 kilobase pairs that were specific for each single-copy probe were identified. Specialized YAC libraries will make many more tumor-specific chromosomal abnormalities accessible to molecular isolation. PMID- 2236074 TI - Actin cores of hair-cell stereocilia support myosin motility. AB - The actin cores of hair-cell stereocilia were tested as a substrate for the movement of myosin-coated beads in an in vitro assay. Large numbers of stereocilia from bullfrog sacculi and semicircular canals were isolated by blotting onto coverglasses and were demembranated to expose the polar actin tracks of their cytoskeletal cores. Silica or polystyrene beads, coated with thick filaments of chicken skeletal muscle myosin, were added to this core preparation in the presence of ATP. Myosin-coated beads could reach some of the cores by diffusion alone, but the efficiency and precision of the assay were improved considerably by the use of "optical tweezers" (a gradient-force optical trap) to deposit the beads directly on the cores. Beads applied in this fashion bound and moved unidirectionally at 1-2 microns/s, escaping the retarding force of the trap. Actin filaments within the stereocilia are cross-linked by fimbrin, but this did not appear to interfere with the motility of myosin. Beads coated with optic-lobe kinesin were also tested for movement; these bound and moved unidirectionally at 0.1-0.2 microns/s when applied to microtubule-based kinociliary cores, but not when applied to actin-based stereociliary cores. Our results are consistent with, and lend support to, a model for hair cell adaptation in which a molecular motor such as myosin maintains tension on the mechanically gated transduction channels. Optical tweezers and video-enhanced differential interference contrast optics provide high efficiency and improved optical resolution for the in vitro analysis of myosin motility. PMID- 2236076 TI - Hypodense eosinophils and interleukin 5 activity in the blood of patients with the eosinophilia-myalgia syndrome. AB - The recent recognition of the eosinophilia-myalgia syndrome (EMS) associated with the ingestion of L-tryptophan prompted an analysis of the peripheral blood eosinophil phenotypes and of the serum eosinophil hematopoietins in this disorder. Five patients with an illness characterized by the abrupt onset of aching skeletal muscles, edema, thickening and induration of the skin, and marked blood eosinophilia associated with L-tryptophan ingestion provided eosinophils, serum, or both, for evaluation. Gradient sedimentation density analysis of the peripheral blood eosinophils from four of these patients revealed that 43 +/- 13% (mean +/- SEM) of the cells had converted to the abnormal (hypodense) sedimenting phenotype. When normodense eosinophils from the reference donors were cultured for 3 days in medium supplemented with increasing concentrations of serum from the patients with EMS, their viability increased in a dose-dependent manner to 45%, which was significantly augmented over the effect of normal serum. This eosinophil viability-sustaining activity was inhibited by 76 +/- 7% (mean +/- SEM; n = 3) by the addition of anti-interleukin 5 (IL-5) but not by neutralizing antibodies monospecific for either granulocyte/macrophage colony-stimulating factor (GM-CSF) or IL-3. IL-5, an eosinophilopoietic factor, converts normodense peripheral blood eosinophils in vitro to a hypodense sedimenting form with extended viability and augmented biologic responses to activating stimuli. Thus, the presence of IL-5 in the sera of patients with EMS may contribute to the development and maintenance of the eosinophilia and may regulate the conversion of the peripheral blood eosinophils to the hypodense phenotype with augmented pathobiologic potential. PMID- 2236077 TI - Enzymatic aminoacylation of an eight-base-pair microhelix with histidine. AB - The major determinant for the identity of alanine tRNAs is a single base pair in the acceptor helix that is proximal to the site of amino acid attachment. A 7 base-pair microhelix that recreates the acceptor helix can be charged with alanine. No other examples of charging of small helices with specific amino acids have been reported, to our knowledge. We show here that a 13-base-pair and an 8 base-pair hairpin helix that reconstruct a domain and subdomain, respectively, of histidine tRNAs can be charged with histidine. We also show that transplantation of a base pair that is unique to histidine tRNAs is sufficient to consider histidine acceptance on a domain and subdomain of alanine tRNA. Both alanine and histidine aminoacyl-tRNA synthetases retain specificity for their cognate synthetic substrates. Alanine- and histidine-specific microhelices may resemble a system that arose early in the evolution of charging and coding. PMID- 2236078 TI - An essential arginine residue for initiation of protein-primed DNA replication. AB - A group of proteins that act as primers for initiation of linear DNA replication are called DNA-terminal proteins (terminal proteins). We have found a short stretch of conserved amino acid sequence among the terminal proteins from six different sources. The location of this sequence motif is also similar among the different terminal-proteins. To determine the functional role of this terminal protein domain in DNA replication, we have studied the bacteriophage PRD1 system. The PRD1 terminal protein and DNA polymerase genes were cloned into expression vectors, and the recombinant plasmids were used for constructing PRD1 terminal protein mutants. Site-directed mutagenesis and functional analysis showed that one of the two arginines (Arg-174) in the conserved sequence is critical for the initiation complex-forming activity of the PRD1 terminal protein. Replacement of Arg-174 by noncharged amino acids resulted in nonfunctional terminal protein. Phenylglyoxal, an alpha-dicarbonyl compound that reacts with the guanidino group of arginine, inhibits initiation complex formation between PRD1 terminal protein and dGMP. On the basis of these results, we propose that Arg-174 represents, at least in part, the binding site for phosphate groups of dGTP. PMID- 2236080 TI - Xenopus laevis alpha and beta thyroid hormone receptors. PMID- 2236081 TI - Boyd Orr memorial lecture. Early nutrition and later achievement. PMID- 2236082 TI - An overview of the epidemiological evidence linking diet and cancer. PMID- 2236079 TI - Mouse transgenes in human cells detect specific base substitutions. AB - We describe a system of transgenic human cell lines that detects and identifies specific point mutations at defined positions within a gene. The target transgenome is a mouse adenine phosphoribosyltransferase (APRT) gene rendered nonfunctional by introduction of a substitution at either of two bases that comprise a splice acceptor site. Reversion at a mutated site results in the expression of wild-type mouse APRT and consequent growth of APRT+ transgenic cell colonies. Site-specific reversion to wild-type sequence is confirmed by regeneration of a previously destroyed diagnostic Pst I site. Two independent cell clones, each with mutant transgenomes bearing an A----G transition, exhibited an up to 7500-fold, dose-dependent induction of reversion following treatment with ethyl methanesulfonate. Treatment of these clones with 2 aminopurine resulted in no induction of revertants. In contrast, another transgenic cell clone, bearing a G----A transition, reverted as a consequence of 2-aminopurine, but not ethyl methanesulfonate, treatment. These data confirm for human cells the proposed mechanisms of action of these mutagens and provide evidence for the utility of our site-specific reversion method for mutagenesis studies. PMID- 2236083 TI - Chemical food contaminants in the initiation of cancer. PMID- 2236084 TI - Alcohol and cancer. PMID- 2236085 TI - Inhibition of carcinogenesis by minor anutrient constituents of the diet. AB - A continuing study of chemopreventive agents has focused on several categories of naturally occurring compounds that inhibit carcinogen activation and are effective in preventing carcinogen-induced neoplasia when administered at short time-intervals before carcinogen challenge. The inhibitory compounds are: aromatic isothiocyanates found in cruciferous vegetables, monoterpenes present in citrus fruits and caraway-seed oil, and organosulphur compounds occurring in Allium species. Preliminary work indicates that glucobrassicin and indoles existing in cruciferous vegetables also have these attributes. Almost all carcinogens that are consumed in food require metabolic activation. Thus, inhibition of carcinogen activation reactions could be effective against this type of exposure. In addition, three naturally occurring compounds, i.e. phenethyl isothiocyanate, D-limonene and dipropyl sulphide inhibit activation of the tobacco-specific carcinogen NNK, and accordingly may have the capacity to diminish carcinogenic response to exposures to tobacco. The property of cruciferous vegetables, orange oil, benzyl isothiocyanate, and D-limonene, to act as both blocking and suppressing agents has been discussed. Two possible mechanisms for this multi-phase activity were presented. The first is that these inhibitory substances activate a complex integrated defence mechanism against toxic compounds which entails both blocking and suppressing components. The blocking component is the initial line of defence, and the suppressing component constitutes a 'fail-safe' backup to assure that if any of the toxic material attacks cellular constituents, its effects will be nullified. The second possible mechanism considered is that the inhibitors, because of high reactivity, have multiple biological effects that are separate and not part of a single, coordinated response. Inhibitors that have both blocking and suppressing effects could be particularly useful as chemopreventive agents. A simple interim classification of foods in terms of their potential impact on the occurrences of cancer has been proposed. PMID- 2236086 TI - Thyroid hormones and thermogenesis. PMID- 2236087 TI - Thermogenesis above maintenance in humans. PMID- 2236088 TI - Dietary-induced thermogenesis and feed evaluation in ruminants. PMID- 2236090 TI - Fatty acids, lipid peroxidation and diseases. PMID- 2236089 TI - Iron free radicals and arthritis. PMID- 2236091 TI - Cell lineage and differentiation during growth of the early mammalian embryo. PMID- 2236092 TI - Dietary methodology: implications of errors in the measurement. PMID- 2236093 TI - The Northern Ireland dietary survey and related studies. PMID- 2236094 TI - Dietary patterns in the Belfast MONICA Project. PMID- 2236095 TI - Nutrient intakes in socially disadvantaged groups in Ireland. PMID- 2236096 TI - Sodium and potassium intakes in Ireland. PMID- 2236097 TI - Nutritional surveillance in Ireland: theory and practice. PMID- 2236098 TI - Casein: a milk protein with diverse biologic consequences. AB - The consequences of bovine milk consumption are diverse, some of which are potentially deleterious. Although certain cultures shun cow's milk or milk-based products, Western societies consume large quantities of cow's milk. Although there are stronger similarities between bovine whey proteins and human whey proteins, the quantity and nature of casein in cow's milk differ markedly from human milk. We propose that the consequences of diets based on bovine casein should be more closely evaluated and certainly expanded beyond the simplistic approach of growth. What is good for the goose may be good for the gander, but what is good for the cow could be harmful to the human. PMID- 2236100 TI - Disintegrins: a family of integrin inhibitory proteins from viper venoms. AB - Disintegrins represent a new class of low molecular weight, RGD-containing, cysteine-rich peptides isolated from the venom of various snakes. They interact with the beta 1 and beta 3 families of integrins and their potency is at least 500-2000 times higher than short RGDX peptides. Analysis of the amino acid sequences of 14 different disintegrins suggests that the RGD sequence, in the spatial configuration determined by the appropriate pairing of the cysteine residues, functions as a cell recognition site. However, certain nonconserved amino acids appear to modify the activity of disintegrins, their specificity for various receptors, and their ability to compete specifically with various ligands. PMID- 2236099 TI - The biology of mesangial cells in glomerulonephritis. AB - It is likely that a complex bidirectional interaction occurs between mesangial cells and the immune cells which infiltrate the mesangium during nephritis. Macrophages and other immune cells liberate a series of mediators, including substances such as IL-1, beta-endorphin, TNF, and PDGF--all of which promote the growth of mesangial cells. The end result is mesangial cell proliferation and increased matrix production, both of which are seen in nephritis. The proliferating mesangial cells liberate autocoids such as IL-1 and PDGF, thereby setting up an amplifying loop. Simultaneously, suppressive factors such as TGF beta are released which antagonize the actions of these growth-promoting substances. The proliferating mesangial cells also produce immunomodulatory peptides, which will in turn act on the infiltrating macrophages to stimulate their replication and activation. Such activated macrophages continue to amplify the inflammatory lesion and also promote the phagocytosis of localized antigen antibody complexes. The net effect of all of these interactions will depend on the dominance of substances which persist and override the roles of other molecules. Studies of the controls which regulate the production of these growth factors/immune modulators will yield insights into the fundamental mechanisms which determine the outcome in glomerulonephritis. PMID- 2236101 TI - Interleukin 6 in infection and cancer. PMID- 2236102 TI - Effects of recombinant human interleukins on food intake of previously food deprived rats. AB - The effects of intracerebroventricular injection of recombinant human interleukin 1 beta (rhIL-1 beta), 1 alpha (rhIL-1 alpha), and 2 (rhIL-2) on feeding behavior were examined in previously food-deprived rats for 18 hr. At doses of 2-17 ng/rat, rhIL-1 beta significantly reduced food intake in a dose-dependent manner and the feeding suppression continued about 4 hr later. Only 17 ng/rat rhIL-1 beta reduced body weight gain for 8 hr after the injection. However, rhIL-1 alpha at dose of 17 ng/rat did not show any significant change of food intake and body weight gain during the whole observation period. At both doses of 8 and 40 ng/rat, rhIL-2 also failed to suppress overfeeding after food deprivation. In adrenalectomized rats, feeding suppression by rhIL-1 beta appeared at the 1- to 2 hr time period. The present studies suggest that rhIL-1 beta may be, at least in part, involved in feeding suppression on various inflammatory processes and that adrenal hormones may not play an important role in the induction of feeding suppression by rhIL-1 beta. PMID- 2236103 TI - Role of parathyroid hormone in the decreased motor nerve conduction velocity of chronic renal failure. AB - Certain data support the notion that chronic exposure to excess parathyroid hormone (PTH) is associated with decreased motor nerve conduction velocity, while other studies failed to confirm such an effect. Also, chronic renal failure of 4 months duration in dogs did not elicit changes in MNCV or calcium content of nerve. These discrepancies may be due to differences in other metabolic parameters, such as degree of uremia, serum levels of calcium, phosphorus, or magnesium, and acid-base parameters, or in duration of chronic renal failure. To examine the effect of PTH on peripheral nerve function in renal failure in a more defined biochemical setting, we studied the changes in MNCV and nerve calcium content in dogs with and without excess PTH and with prolonged and similar duration of chronic renal failure (57 +/- 1.7 weeks) and comparable biochemical parameters. Dogs with chronic renal failure displayed a significant (P less than 0.01) decrease in MNCV (before renal failure, 65 +/- 1.5 m/sec; after renal failure, 49 +/- 3.5 m/sec) and marked elevation in calcium content of peripheral nerve (444 +/- 45 mg/kg dry wt). These derangements were not observed in parathyroidectomized chronic renal failure animals; MNCV before renal failure was 66 +/- 1.5 m/sec and after renal failure was 65 +/- 1.5 m/sec, and nerve calcium content after renal failure was 229 +/- 3 mg/kg dry wt. Also, parathyroidectomy of three dogs with preexisting chronic renal failure of 52 weeks was associated with reversal of the abnormalities in MNCV and calcium content of nerve despite an additional period of renal failure of 52 weeks in two of the dogs and 40 weeks in the third. Our data are consistent with the proposition that excess PTH plays a major role in the genesis of peripheral nerve dysfunction in chronic renal failure. This adverse effect of the hormone is most likely mediated by the PTH induced accumulation of calcium in peripheral nerve. PMID- 2236104 TI - Stimulation of radiation-impaired plasminogen activator release by phorbol ester in aortic endothelial cells. AB - Ionizing radiation has been reported to affect the fibrinolytic activity of exposed tissue. With cultured bovine aortic endothelial cells, radiation suppresses the release of plasminogen activator to the conditioned media, with a concomitant increase in intracellular plasminogen activator. Thus study was undertaken to determine whether radiation-impaired plasminogen activator release can be modified by phorbol ester. We exposed cultured bovine aortic endothelial cells to a sterilizing dose of 10 Gy of gamma-rays and found the treatment led to cell injury, as evidenced by an increased release of prelabeled chromium, and to a reduction of plasminogen activator in the conditioned media with elevated intracellular plasminogen activator in irradiated cells. Phorbol ester enhanced plasminogen activator activity in both sham-irradiated and irradiated endothelial cells. It was interesting to note that the increased plasminogen activator in phorbol ester-stimulated sham-irradiated cells was largely retained inside the cell, while it was released to the conditioned media in irradiated cells. Apparently, altered plasminogen activator activity of radiation-sterilized endothelial cells can be modified by exogenous stimuli. PMID- 2236105 TI - The effect of dietary protein source on manganese bioavailability to the rat. AB - Rats were fed diets containing 20% protein from casein, beef, chicken, tuna, or soybean. All diets contained 15% fat and were supplemented with limiting amino acids as necessary to meet National Research Council requirements. In Experiment 1, the manganese content of all diets was the same; manganese content was 5 mg/kg. In Experiment 2, a basal (adequate) level of minerals was provided in each diet but total mineral content varied depending on the contribution of the protein source; manganese was added to achieve a concentration of 5 mg/kg. In both experiments, 54Mn absorption was greatest from tuna (8.54% and 7.71%) and least from beef (4.57% and 4.14%) (P less than 0.0001). In both experiments, biologic half-life of 54Mn was longest in rats fed beef (18.5 and 26.9 days) and shortest in rats fed soy (14.5 and 16.2 days) (P less than 0.0002). Except for beef, biologic half-life was similar for dietary groups between the two experiments. In Experiment 1, only kidney manganese concentration was significantly affected by diet and was highest in soy-fed animals. In Experiment 2, plasma, kidney, and liver manganese were all significantly affected by diet and were highest in soy-fed animals and lowest in beef-fed animals. PMID- 2236106 TI - Heparin mediates transmembrane potassium transfer in hyperkalemic dogs. AB - Unheparinized, ureter-ligated control dogs that are potassium loaded, i.e., infused with 2 mEq of KCl/kg until prelethal electrocardiographic changes of hyperkalemic cardiotoxicity appear (end point), transfer 57 +/- 4% (1.7 +/- 0.1 mEq/kg) of administered potassium to intracellular fluid. Heparinized controls transfer 73 +/- 1% (3.2 +/- 0.2 mEq/kg); with simultaneous alpha-adrenoreceptor blockade, that proportion increases to 81 +/- 2% (4.80 +/- 0.7 mEq/kg) and with simultaneous beta-receptor blockade it is 58 +/- 3% (1.1 +/- 0.1 mEq/kg). In potassium loaded, ureter-ligated dogs, heparin increases transmembrane potassium transfer as effectively as does a dosage of atropine large enough to cross the blood-brain barrier and its influence on potassium transfer, like that of atropine, is suppressed by beta-adrenoreceptor blockade. PMID- 2236107 TI - Relaxin, oxytocin, and prostaglandin effects on progesterone secretion from bovine luteal cells during different stages of gestation. AB - To determine the effects of relaxin, oxytocin, and prostaglandin F2 alpha on progesterone secretion, bovine luteal cells from different stages of gestation were dispersed in Medium 199 with 200 units/ml penicillin, 1.0% kanamycin, 0.5% bovine serum albumin, and 400 units/ml collagenase. Cells (10(5) were cultured in 400 microliters of Dulbecco's modified Eagle's medium and Ham's F-12 medium containing fetal bovine serum and antibiotics, in Falcon multiwell plates, in a humidified environment of 95% O2 and 5% CO2 at 37 degrees C. Cells were cultured for 24 hr without treatment and thereafter with medium-hormone replacement every 24 hr. Progesterone was quantified from unextracted media by radioimmunoassay. Basal progesterone secretion after 24 hr was 1.81 +/- 0.14, 1.76 +/- 0.17, 0.54 +/- 0.49, and 0.57 +/- 0.21 pg/ml per viable luteal cell from 145-, 165-, 185-, and 240-day-old corpora lutea, respectively. Basal progesterone secretion increased (P less than 0.05) with time in culture. Relaxin induced a dose dependent (greater than 100 ng/ml) increase in progesterone release, compared with the controls. Oxytocin and prostaglandin F2 alpha induced greater release (P less than 0.05) of progesterone than relaxin at all stages of gestation, but progesterone release was dependent on the stage of gestation and the duration in culture. Luteinizing hormone (100 ng/ml) stimulated whereas 17 beta-estradiol (50 ng/ml) inhibited progesterone secretion by luteal cells at all stages of gestation examined. Relaxin obliterated the prostaglandin- and oxytocin-induced progesterone secretion by bovine luteal cells from 145 to 214 days of gestation. Thus, relaxin, cloprostenol, and oxytocin regulate progesterone production by cultured bovine luteal cells, but hormone secretion was dependent on the stage of gestation. PMID- 2236109 TI - Bile acids in rat serum as indicators of hepatotoxicity by hornet venom. AB - The effect of hornet venom sac extract (VSE) on hepatic function in rats was evaluated by measurement of bile acid (BA) levels. A significant dose-dependent elevation of BA in rat serum upon repeated VSE administration was found. Rats envenomed for 2 weeks showed a significant rise of serum BA compared with the controls or with rats envenomed for 6 days. In rats envenomed for 1 week and killed after another week without envenomation, an improvement of the biochemical status was observed. These observations demonstrated that BA levels reflect the VSE-induced hepatic injury. They suggest that the cholestatic effects of VSE may be due to an impairment of bile acid excretion, but the elevations could also reflect parenchymal hepatic injury. PMID- 2236108 TI - Dietary palmitic acid (16:0) enhances high density lipoprotein cholesterol and low density lipoprotein receptor mRNA abundance in hamsters. AB - In order to examine the qualitative effect of different fats and specific fatty acids on plasma lipids and lipoprotein metabolism, six low fat, cholesterol-free diets were fed to young male hamsters (10/group) for a 4-week period. Fat blends were formulated with coconut oil, palm oil, soybean oil, high oleic acid safflower oil, butter, corn oil, and canola oil. Diets contained 13% energy as fat and dietary polyunsaturate/saturate ratios ranged from 0.12 to 1.04, one of which incorporated the American Heart Association-recommended concentrations of saturates, monoenes, and polyenes and another reflected the current American Fat Blend. In three diets the polyunsaturate/monounsaturate/saturate ratio was held constant while only the 12:0, 14:0, and 16:0 were varied. Plasma lipoproteins and apoproteins were assessed in conjunction with the abundance of specific hepatic and intestinal mRNA for the low density lipoproteins (LDL) receptor and various apolipoproteins associated with cholesterol metabolism. The plasma cholesterol response was lowest with the American Heart Association blend and equally elevated by the more saturated, low polyene diets (polyunsaturate/saturate, 0.12 0.38). Replacing 12:0 plus 14:0 from coconut oil with 16:0 as palm oil induced a significant increase in high density lipoprotein (HDL) cholesterol with a trend toward decreased LDL. These shifts in lipoprotein cholesterol were corroborated by measures of the LDL/HDL ratio, the plasma apolipoprotein B/apolipoprotein A1 ratio, and differences in the synthesis of apolipoproteins and the LDL receptor based on estimates of the mRNA for these proteins in the liver and gut, using specific cDNA probes for apolipoprotein A1, apolipoprotein B, apolipoprotein E, and the LDL receptor. Although it has been suggested that dietary polyenes lower total plasma cholesterol, including HDL, and that saturated fat increases both these pools of cholesterol, the current data represents the first evidence that a specific saturated fatty acid, i.e., palmitic acid, may enhance HDL production. PMID- 2236111 TI - Can hypoglycaemic attacks be avoided? PMID- 2236112 TI - A better life than before--quality of life in people with renal failure. AB - We take it for granted that one of the objectives of nursing is to improve patients' quality of life, but this is notoriously difficult to define. A surgery of renal patients revealed some surprising results of what they considered to constitute quality of life, with implications for the future of nursing care. PMID- 2236113 TI - A case for accuracy--monitoring blood pressure. PMID- 2236110 TI - Two separate differentiation inducing proteins for human myeloid leukemia cells and their isolation from normal lymphocytes. AB - Conditioned medium from mitogen stimulated normal peripheral blood lymphocytes (PBL) has been demonstrated to contain a maturation inducer activity mediating the differentiation of human myeloid leukemia cells to monocytes and macrophages. The maturation inducer activity was isolated by salt precipitation, Sepharose CL 6B ion exchange and affinity chromatographies and electrophoresis. Two separate activities with M.W. ranges of 52-56 and 32-35 kDa capable of mediating the terminal differentiation of leukemic HL-60 promyelocytes to monocytes and macrophages were detected. The higher molecular weight species was determined to be a 54 kDa single polypeptide and was found to be distinct from IL-3 and IL-6 by ELISA and differentiation blocking assay. The inducing activity of the 32-35 kDa material was largely neutralized after treatment with anti-IL-3, but not with other antibodies. Employing the immunofluorescent antibody technique, the 54 kDa protein was detected on the surface membranes of PBL. The proportions and number of maturation inducer bearing lymphocytes in patients with acute myelogenous leukemia (0.4% and 35/mm3, respectively) were significantly lower than that of healthy donors (7.9% and 178/mm3) The role of these physiological factors in leukemia cell differentiation is discussed. PMID- 2236114 TI - Responding to a human need--lecturer-practitioner in human sexuality. AB - It is well known that illness can have a traumatic effect on sexuality. Lecturer practitioners in sexuality help people come to terms with this, and help nurses respond more effectively. PMID- 2236115 TI - Good food for long life--nutrition for elderly people. AB - As the body changes with age, elderly people can become vulnerable to the threat of malnutrition. Nurses can help point out any danger signs, showing them the way towards a healthy and accessible diet. PMID- 2236116 TI - Time to hand over the baby--parental care of the preterm infant. AB - Parents of babies in neonatal units often feel distanced from their baby, saying there is nothing they can do to help. Staff in NNUs must help involve parents in the care of their baby, to soothe qualms about discharge. PMID- 2236117 TI - If your baby is in a neonatal unit. PMID- 2236118 TI - Getting by without the poultices. PMID- 2236119 TI - Consider the mind as well as the body. Nursing care and support in multiple sclerosis. PMID- 2236120 TI - Spatial distribution of taurine in the teleost retina and its role in retinal tissue regeneration. PMID- 2236121 TI - Nervous tissue growth and differentiation: taurine effect on polyamine metabolism. PMID- 2236122 TI - Effect of glutamyltaurine on calcium influx in cultured cerebellar granule cells. PMID- 2236123 TI - Taurine interactions with ionic conductances in excitable membranes. PMID- 2236124 TI - Effects of taurine on mammalian skeletal muscle fiber during development. PMID- 2236125 TI - The interaction between taurine, calcium and phospholipids: further investigations of a trinitarian hypothesis. PMID- 2236126 TI - Inhibitory and stimulatory effects of structural and conformational analogues of taurine on ATP-dependent calcium ion uptake in the rat retina: deductions concerning the conformation of taurine. AB - A number of novel analogues of taurine were tested in a rat retinal preparation for their stimulatory or inhibitory activity in the ATP-dependent calcium ion uptake system at low calcium ion concentration. While the structural requirements for maintaining biological activity were quite limited, certain sulfone derivatives of taurine were observed to be more potent stimulators of calcium ion uptake than taurine. Utilization of multiple effectors in the uptake system was also analyzed. The effects of all combinations of taurine plus analogue that were tested were demonstrated to be mutually exclusive, that is, the compounds have similar modes of action. When two inhibitors, TAPS and THQS, were tested in combination, kinetic evaluation of the data suggested that both of these compounds also have a similar mode of action (mutually exclusive) with respect to each other. The inhibitors, TAPS and THQS, were also observed to be non competitive with respect to taurine thus suggesting that they do not bind to the same site as taurine. PMID- 2236127 TI - Modulation of cardiac Ca++ current by taurine. PMID- 2236128 TI - Immunocytochemical visualization of taurine-containing and taurine-synthesizing cells. PMID- 2236129 TI - Regulation of calcium homeostasis by taurine: role of calmodulin. PMID- 2236130 TI - Calciumdiacetylhomotaurinate (CA-AOTA) decreases the action of excitatory amino acids in the rat neocortex in vitro. PMID- 2236131 TI - Uptake and release of taurine--an overview. PMID- 2236132 TI - Taurine: uptake by platelets and plasma concentration of patients with Spielmeyer Vogt disease. PMID- 2236133 TI - Chloride-dependent amino acid transport in synaptic membrane vesicles. PMID- 2236134 TI - Taurine transport and cell volume regulation in a mammalian cell. PMID- 2236135 TI - A developmental and functional study on taurine-like immunoreactivity in the rat retina. PMID- 2236136 TI - Characteristics of taurine release from astroglial cells. PMID- 2236137 TI - Ionic and voltage requirements for tubular taurine transport. PMID- 2236138 TI - Taurine and mechanisms of cell volume regulation. PMID- 2236139 TI - Acclimation to hyper- and hypo-osmotic changes: the anomalous behavior of taurine in the nervous system and in the blood of vertebrates. PMID- 2236140 TI - Derangements in cerebral osmohomeostasis: a common denominator for stimulation of taurine and phosphoethanolamine release. PMID- 2236141 TI - Osmotic sensitivity of isoproterenol- and high-[K+]o-stimulated taurine release by cultured astroglia. PMID- 2236142 TI - Possible osmoregulatory role of taurine in the cellular swelling evoked by weak organic acids in the rat hippocampus. PMID- 2236143 TI - Taurine release associated to cell swelling in the nervous system. PMID- 2236145 TI - Taurine deficiency. PMID- 2236146 TI - Effects of taurine depletion on excitable tissues: recent studies. PMID- 2236144 TI - Is taurine involved in cerebral osmoregulation? PMID- 2236148 TI - Taurine deficiency myocardial failure in the domestic cat. PMID- 2236147 TI - Visual cortex development in rhesus monkeys deprived of dietary taurine. PMID- 2236149 TI - Evaluation of immunity in taurine-deficient cats. PMID- 2236150 TI - The effect of dietary taurine on feline reproduction and outcome. PMID- 2236152 TI - Taurine levels in brain nuclei of young adult and aging rats. PMID- 2236151 TI - Homeostatic and protective effects of taurine. PMID- 2236153 TI - Influence of dietary sulfur-containing amino acids on renal function and metabolism of calcium and taurine in chronic renal failure. PMID- 2236154 TI - Central antihypertensive effect of taurine. PMID- 2236155 TI - Tauret: further studies of the role of taurine in retina. PMID- 2236157 TI - Taurine and volume regulation in fish cells. PMID- 2236156 TI - Mitochondrial stability in taurine perfused, hypoxic bovine eye. PMID- 2236158 TI - Cysteine sulfinic acid decarboxylases (CSD) in the brain. PMID- 2236159 TI - Does taurine bind to the insulin binding site of the insulin receptor? PMID- 2236160 TI - Modelling the effect of chemotherapy intensity. PMID- 2236161 TI - Comments on kinetics and biology of the residual cancer, and on relevant therapeutic strategies based on these phenomena. PMID- 2236162 TI - Intraperitoneal chemotherapy for peritoneal carcinomatosis from colonic or appendiceal cystadenocarcinoma: rationale and results of treatment. AB - The natural history of cystadenocarcinoma of colonic or appendiceal origin was reviewed. This tumor represents a minimally invasive mucus producing tumor similar to what is commonly recognized within the bowel lumen as villous adenoma. This tumor is usually at an advanced stage at the time of presentation, and tends to recur at the site of tumor resection and on peritoneal surfaces. The fact that this tumor does not metastasize hematogenously or lymphatically nor does it invade locally was contrasted to its marked tendency to implant on all abdominal surfaces. The large variations in the efficiency of different types of tumor dissemination (metastases, invasion, and spread by implantation) need to be noted for this malignant process. The unique clinical features of cystadenocarcinoma were reviewed and the particular suitability of intraperitoneal chemotherapy for its treatment was discussed. Our treatment plan utilizing cytoreductive surgery and early plus delayed postoperative intraperitoneal chemotherapy was presented. The surprisingly good results of treatment was discussed. The effects of chemotherapy on tumor histology were presented in detain in six patients. Changes induced by intraperitoneal chemotherapy included a reduction in the number of foci of atypical adenomatous epithelium and marked cytologic atrophy. This plan of treatment is recommended for patients to prevent or to treat the spread of mucinous gastrointestinal cancer on peritoneal surfaces and within the resection site of the primary tumor. PMID- 2236163 TI - Autologous bone marrow transplantation for hematologic cancer. AB - In summary, autologous BMT is emerging as a way to deliver myeloablative therapy to patients with hematologic cancer ineligible for allogeneic BMT. Moreover, there are likely circumstances in which autologous is preferable to allogeneic BMT--most notably in Hodgkin's disease, but likely also in the older adult acute leukemia patient. Work is clearly required to produce upgraded conditioning regimens, and to define the need for and utility of marrow purification procedures. However, these pressing needs should not obscure the benefits of the current use of autologous BMT techniques for selected patients--nor prevent the realization that improved patient selection is the most immediate method to improve current results. PMID- 2236164 TI - Dose intensification using combination alkylating agents and autologous bone marrow support in the treatment of primary and metastatic breast cancer: a review of the Duke Bone Marrow Transplantation Program experience. PMID- 2236165 TI - Tumor treatment and cytokines. AB - In summary, molecular biology and advances in biochemical and biological techniques have led to the rapid characterization of a large number of cytokines. These are released in response to injury or invasion of the body and regulate the growth and function of a broad variety of cell types. Many cytokines are now in clinical trials and show promise in modulating the defence and repair responses of the body. The direct application of these cytokines to the killing of tumor cells remains problematic. However, it does seem likely that the use of these substances in a para-physiological mode i.e. in activating defence mechanisms and in particular stimulating hemopoetins may be a very important adjunct to more conventional means of tumor therapy such as chemotherapy or radiotherapy. The hemopoietic growth factors show particular promise here, although other substances such as IL-1 or IL-6 may find similar applications. In the future more information on the direct role of cytokines in the development of particular tumors may lead to the development and use of cytokine antagonists with effects directed at tumor cells or their environment. PMID- 2236166 TI - Dose intensity studies in breast cancer--autologous bone marrow transplantation. PMID- 2236167 TI - Use of granulocyte-macrophage colony stimulating factor (GM-CSF) to support intensive chemotherapy. PMID- 2236168 TI - Induction of secondary neoplasms by the treatment of malignant disease: lessons from Hodgkin's disease. PMID- 2236169 TI - Overview of adjuvant radiotherapy for breast cancer. PMID- 2236170 TI - Measuring quality of life. PMID- 2236172 TI - Comments on future developments of cancer therapy. Taking into consideration tumor biology and kinetics. Part II. PMID- 2236171 TI - Chemotherapy schedules: impact on treatment outcomes and quality of life. PMID- 2236173 TI - The biological basis for interleukin-2 anticancer therapy. PMID- 2236174 TI - The growth kinetics of clonogenic tumor cells that survive radiation therapy. PMID- 2236175 TI - Microenvironmental changes in irradiated tumors. PMID- 2236176 TI - The nature of tumour hypoxia: implications for therapy. PMID- 2236177 TI - Integrating the concept of dose intensity into a strategy for systemic therapy of malignant disease. PMID- 2236179 TI - Thin layer densitometry in the quantitative assay of drugs. Note V--Assay of reserpine and chlorthalidone in the presence of the potential impurities of their solid pharmaceutical forms. AB - Densitometric detection of compounds separated by thin layer was applied to the assay of a mixture of reserpine and chlorthalidone and their possible impurities. The method of analysis gave satisfactory results in the quality control of pharmaceutical preparations. Good results were obtained in urine tests for the detection of chlorthalidone, reserpine and methylreserpate. The times for the development of fluorescence in reserpine and methylreserpate directly in the chromatographic plate, are also described. PMID- 2236178 TI - [The effect of food intake on drug action]. AB - Interactions between medicaments and food are only incompletely documented- despite their frequent occurrence. Food can influence the effect of medicaments in a variety of ways: the effect of the medicament can be delayed or weakened; in some cases the effect may also be increased. The interactions between the kinetics of medicaments and food are described in the present survey. The absorption conditions in the stomach and small intestine are influenced physiologically and chemically by food. In very rare cases the elimination of active ingredients too can be modified by the quality and quantity of the food. Detailed knowledge about the physical-chemical properties of the medicaments used help to optimize the pharmacotherapy in the individual case. For the patient, the easiest suggestion to follow would be to take the medicaments with plenty of water and always at the same time. PMID- 2236180 TI - [Synthesis and anticonvulsant properties of sugar triazene N-oxides]. AB - In this paper we describe a high-yielding method leading to a novel family of sugars: the sugar triazene N-oxides. The anticonvulsant effect of one of these compounds was tested. It showed a promising activity indicating the potential therapeutic usefulness of this class of carbohydrate derivatives. PMID- 2236181 TI - Comparison of colourimetric methods for ammonia determination. AB - The precision of the Berthelot and Nessler methods of ammonia determination are compared at various ammonia concentrations. Recommendations are made regarding the most appropriate technique to use, dependent on the range of ammonia concentration expected. The effect of microdiffusion separation on the precision of ammonia determination is studied, together with an evaluation of a water soluble lid sealant and of the effect of a model amine contaminant. PMID- 2236182 TI - Effect of beta-cyclodextrin on the in vitro permeation rate and in vivo rectal absorption of acetaminophen hydrogel preparations. AB - The amounts of beta-cyclodextrin and hydroxyl propyl methyl cellulose (HPMC) affecting the in vitro permeation rate of acetaminophen containing in both aqueous solutions and HPMC hydrogel preparations through the dialyzer tubing and isolated rat rectum were investigated. The partition coefficient of acetaminophen with or without beta-cyclodextrin in water/n-octanol system was also studied. In vivo absorption experiments of these test formulations were carried out by rectal administration in rats. The results indicate that the concentrations of beta cyclodextrin and HPMC used decreased the amount permeated of acetaminophen from both test formulations. The more the amount of beta-cyclodextrin or HPMC the slower the permeation rate of acetaminophen. The permeation rate of acetaminophen through the dialyzer tubing was higher than that of acetaminophen through the isolated rat rectum. The result also shows beta-cyclodextrin and HPMC markedly reduced the in vivo bioavailability of acetaminophen from both test formulations. The lower partition coefficient and the higher hydrophilic properties of beta cyclodextrin inclusion complex, and the higher viscosity of HPMC hydrogel matrix might be responsible for decreasing the in vitro permeation rate and depression of in vivo rectal absorption of acetaminophen. The in vitro permeation data was well correlated with in vivo absorption results, suggesting that the in vitro permeation study regardless of the dialyzer tubing method or the isolated rat rectum method might be used to estimate the in vivo rectal absorption of acetaminophen. PMID- 2236183 TI - [Dietetic use of red sugarbeet pigment--effervescent tablets]. PMID- 2236184 TI - [Spectrum analysis and thermal behavior of P.E.G. 6000 in the presence of antipyrine or pyramidon]. PMID- 2236185 TI - [The Pharmaceutical Institute in Berlin. The development of pharmaceutical education to the present professional pharmacy]. PMID- 2236186 TI - [Pharmacy history--a science with two histories]. PMID- 2236187 TI - [Hermann Thoms and the pharmaceutical-chemical literature]. PMID- 2236188 TI - [Pharmacy research by Schering: a good foundation for the next century]. PMID- 2236189 TI - [Synthetic drugs of abuse of the second generation (so-called designer drugs). 2. Analysis of arylalkylamines (amphetamine)]. PMID- 2236190 TI - [Platelet activating factor--a biologically active phospholipid]. PMID- 2236191 TI - Nonsteroidal antiinflammatory agents. Part 20(3): Optically active thienyl biphenylyl-hydroxypropionic acids. AB - The optically active diastereometric erythro- and threo-3-thienyl-analogues 6a-d of 3-aryl-2-biphenylyl-3-hydroxy-propionic acids have been prepared. Some stereoisomers of 3-(3-thienyl)derivative 6b showed inhibition around 40% in the carrageenan-induced rat paw edema test. PMID- 2236193 TI - [Computer-aided differential thermal analysis of drugs]. AB - An open-loop on-line computer connection to a DTA apparatus of high time constant and the developed software for data acquisition and utilization are described. The new system was calibrated thermomentrically and calorically. The main aim is a enhanced purity estimation, especially by using of the modified Van't Hoff equation based on DTA curves, which first must be transformed to process-power curves. Computer aided DTA provides utilization of higher quality and makes them faster and more exactly. Plotting of DTA curves which are baseline corrected and constructed as mean of equal curves as well as zooming are powerful and essential tools in optical comparison. The better estimation of the baseline under the peak and the computation of process-power-curve from DTA curve enable estimations based on curves of DTA apparatus' with high time constant as like as bases on DSC curves. PMID- 2236192 TI - Synthesis and pharmacological activity of 2-alkylthio substituted thieno[2,3 d]pyrimidine-4-one and 5H-pyrimido [5,4-b]indol-4-one. AB - Quaternary salts of several 2-alkylthio substituted derivatives of thieno [2,3 d]pyrimidin-4-one and 5H-pyrimido [5,4-b]indol-4-one with a basic group in position 2 of the alkyl chain were synthesized and screened for potential spasmolytic activity. These substances were prepared by condensation of the corresponding mercapto compounds with a 2-chloroalkyltertiary amine. The tertiary bases were quaternized with methyl iodide. Among the assayed compounds, the thieno [2-3-d]pyrimidin-4-one derivatives displayed a potent spasmolytic activity in the in vitro and in vivo assays. PMID- 2236194 TI - Percutaneous diffusion of cefalexin, sulfamethoxazole and diphenhydramine from ointments. AB - The effects of ointment base, drug concentration, and the presence of surfactant on the diffusion of cefalexin, sulfamethoxazole and diphenhydramine through excised mouse skin were studied. The total amount of diffused drug per ml against time and against the square root of time as plotted for the evaluation of results. As was expected from theory, a linear relationship was obtained for each drug when the square root of time was employed. The effect of the vehicle on the release of cefalexin was in the following decreasing order: o/w emulsion greater than water-soluble greater than hydrophilic greater than oleaginous greater than w/o emulsion base. That on the release of sulfamethoxazole was in the order: water-soluble greater than o/w emulsion greater than w/o emulsion = oleaginous = hydrophilic. The order in case of diphenhydramine was as follows: o/w emulsion greater than water-soluble greater than hydrophilic greater than oleaginous = w/o emulsion. The increase in drug concentration or the addition of a surfactant has caused an increase in the diffusion rate of each of the drugs. PMID- 2236195 TI - [Is the estimation of the activity of MTT-reduction suitable for the determination of basal cytotoxicity?]. AB - The influence of 19 substances on the reduction of thiazolyl-blue (MTT) by cultivated calf aortic endothelial cells was studied. The substances tested could be classified into three groups. The first one includes drugs without significant effect on the reduction of MTT, the second one inhibits these reaction only weakly (less than 50%) and 10 substances of the third group showed an inhibition rate greater than 50%. There is no statistical reliability in the correlation between the IC50-values of the substances studied in the MTT-test and their LD50 values (mouse, per os). The MTT-test does not permit the estimation of the basal cytotoxicity but only the inhibition of the activity of succinate dehydrogenase and the cytochrome c/c1-complex of the respiration chain of cultivated endothelial cells. PMID- 2236196 TI - [Judicial protection of monoclonal antibodies]. AB - The possibility for GDR application for a patent of monoclonal antibodies are discussed in detail. Antibodies can be used advantageously as diagnostica. Basic suppositions for true patents in this field e.g. sufficient manifestation of the invention, newness and ingenious performance are referred. Possible algorithms for the formulation of the claims are given. PMID- 2236197 TI - [In vitro liberation of sulfadimidine from granulations and capsules]. PMID- 2236198 TI - [Pharmaceutical and biopharmaceutical evaluation of acetylaminonitropopoxybenzolum (Falimint). 10. Biotransformation of the active substance in chick embryo and in in vitro systems]. PMID- 2236199 TI - [Comparative study of serum levels of salicylic acid after oral administration of salicin and sodium salicylate in rats]. PMID- 2236200 TI - [Comparative structure-activity and structure-toxicity of a series of 2,4 oxazolidinediones]. PMID- 2236201 TI - [Toxicity of Aethusa cynapium L., hundspetersilie]. PMID- 2236202 TI - Effect of 2-mercapto-ethanol on some brain biochemical characteristics and behavioural changes in the ageing CBA/Ca mice. AB - Male CBA/Ca inbred mice were treated with a dose of 8 micrograms 2-mercapto ethanol per animal per day in the drinking water from the age of 5 months onwards up to the age of 24 months. Dopamine release was greatly decreased in old animals in contrast to the elevation of dopamine release in the treated mice. Similarly, an elevated malondialdehyde content in brain homogenates was also observed in the aged treated animals compared with their controls. No essential differences were observed in locomotor activity and learning between treated an control mice. PMID- 2236203 TI - Effect of diltiazem on experimental coronary artery thrombosis in dogs. AB - The effect of the calcium channel blocker diltiazem on arterial thrombosis was determined in anesthetized dogs subjected to continuous anodal stimulation of the intimal surface of the left circumflex coronary artery (LCCA). Infusion of saline (n = 6) or diltiazem (80 micrograms/kg plus 20 micrograms/kg/min i.v.; n = 6) was begun 15 min before electrical stimulation. Diltiazem prolonged the P-R interval by 28% and reduced mean arterial blood pressure (ABP) by 9%. All animals developed occlusive thrombosis. Saline- and diltiazem-treated dogs did not differ in the time to occlusion (204 +/- 30 and 153 +/- 27 min, respectively) and LCCA thrombus mass (25 +/- 4 and 24 +/- 3 mg, respectively). LCCA flows measured intermittently during thrombogenesis also did not differ between treatment groups, although the frequency of spontaneous flow increases which interrupted the flow declines was reduced 53% by diltiazem. In separate diltiazem-treated dogs (80 micrograms/kg plus 20 micrograms/kg/min i.v. for 2 h; n = 7) the ex vivo platelet aggregation response to platelet-activating factor (PAF) was inhibited ( 45%), but not the response to collagen. When 5 and 25 mumols/l diltiazem was tested in vitro, again the aggregation response to PAF was reduced (-25 and -81%, respectively) while that to collagen was unaffected. These results demonstrate that diltiazem does not impede thrombus formation in vivo when given at a dose that exerts threshold hemodynamic activity and significantly impairs platelet function. PMID- 2236204 TI - Physics of thermal processes in laser-tissue interaction. PMID- 2236205 TI - Monte Carlo calculation of conversion factors for the estimation of mean glandular breast dose. AB - The IPSM report on the commissioning and routine testing of mammographic x-ray systems recommends that breast dose be specified as the mean dose to the glandular tissues within the breast and gives the size and compositions of a standard breast phantom for the comparison of doses. The dose to this standard breast phantom can be determined by measuring the incident air kerma to a Perspex phantom and applying appropriate multiplicative conversion factors. These conversion factors have been evaluated by Monte Carlo calculations for a wide range of mammographic x-ray spectra. Some factors are provided for a range of breast thicknesses to supplement existing tabulations. Results are also given for equivalent thicknesses of Perspex and breast tissue. PMID- 2236206 TI - Measurement of backscatter factors for low energy radiotherapy (0.1-2.0 mm Al HVL) using thermoluminescence dosimetry. AB - Significant discrepancies of up to 10% exist between backscatter factors (BSF) recommended in a recent IAEA dosimetry Code of Practice (1987) compared with those published in Br. J. Radiol. Supplement 17 (1983), for the x-ray quality range 0.1-2.0 mm Al HVL. In an attempt to resolve this discrepancy, BSFs have been measured using thermoluminescence dosimetry (TLD) with small lithium borate chips, in order to minimise displacement effects associated with the use of larger volume ionisation chambers. Although subject to uncertainties inherent in the TLD calibration and readout process, the results indicate that the BJR (1983) data overestimate BSFs in this quality range. Broad agreement with the IAEA data is indicated, for the limited number of x-ray qualities and field sizes used. PMID- 2236207 TI - Cross sections and partial kerma factors for elastic and inelastic neutron scattering from nitrogen, oxygen and calcium at En = 21.6 MeV. AB - The Studsvik high-resolution, low-background time-of-flight facility has been used to measure differential neutron scattering cross sections for nitrogen, oxygen and calcium at a neutron energy of 21.6 MeV. Angular distributions in the range 10 degrees-160 degrees have been measured for both elastic and inelastic scattering from some low-lying levels in the three nuclei. Angle-integrated cross sections have been determined by fitting Legendre polynomial expansions to the differential data. Partial kerma factors for elastic and inelastic scattering have been deduced from these fits. Analyses in terms of the spherical optical model and the distorted-wave Born approximation have provided information on potential parameters and deformations, which have been used to calculate cross sections and partial kerma factors. Comparisons have been made with other recent data sets and model predictions, as well as with the evaluated neutron data file ENDF/B-V. PMID- 2236208 TI - Field dependence of 19F NMR in rat bone powders. AB - The 19F NMR properties of fluoridated rat bone powder samples have been studied in several external magnetic fields. The results show a characteristic field dependence, related to the strength of chemical shift interactions compared to dipole-dipole interactions. While the free induction decay shape is relatively insensitive to the 19F bone mineral concentration, the spin-lattice relaxation time decreases with increasing 19F concentration. Multi-exponential spin-lattice relaxation processes indicate that there are at least two chemically inequivalent incorporation sites for fluorine in bone mineral. Evidence for clustering of 19F fluoride impurities in bone mineral is seen in Hahn echo experiments. Sample preparation and handling methods are shown to affect the values of some of the observed NMR parameters. PMID- 2236209 TI - Calculations of displacement corrections for in-phantom measurements with ionisation chambers for mammography. AB - Displacement corrections for in-phantom measurements with ionisation chambers for the purpose of mammography are large and represent a major correction to consider for dose determinations. Experimental data on displacement corrections depend to a large degree on the model used to extrapolate to zero cavity radius. Calculations of displacement correction factors using a Monte Carlo code are presented for different cavity shapes, i.e. spherical, cylindrical and disc-like, in various phantom materials simulating the average breast and breast composing tissues. In addition, the influence of wall material and depth in-phantom are studied. Exponential extrapolation to zero cavity radius should be performed to obtain the dose in homogeneous phantoms. Displacement corrections for photons as used in mammography seem compatible with geometrical considerations made previously. A discrepancy is found between depth-dose data derived from calculations and those found in experiments. PMID- 2236210 TI - An investigation of factors affecting the accuracy of in vivo measurements of skin pigments by reflectance spectrophotometry. AB - Factors affecting the accuracy of the in vivo measurement of cutaneous pigments and blood oxygenation by reflectance spectrophotometry have been examined. It was found that stray light, the amounts of haemoglobin and melanin, and the level of blood oxygenation all contributed to the measured reflectance and had to be taken into account when calculating quantitative indices of skin pigments. Measurements on isolated sheets of epidermis demonstrated that over 50% of normally incident radiation is transmitted in a forward direction within 17 degrees of the incident direction and approximately 20% is backscattered between 90 degrees and 180 degrees out of the sample, approximately 6.0% of it by specular reflection at the surface. The effective optical pathlength in suspensions of whole red cells was found to be 7% greater than in simple solutions containing the same concentration of haemoglobin. PMID- 2236211 TI - Optical properties of normal and diseased human breast tissues in the visible and near infrared. AB - The optical absorption and scattering coefficients have been determined for specimens of normal and diseased human breast tissues over the range of wavelengths from 500 to 1100 nm. Total attenuation coefficients were measured for thin slices of tissue cut on a microtome. The diffuse reflectance and transmittance were measured for 1.0 mm thick samples of these tissues, using standard integrating sphere techniques. Monte Carlo simulations were performed to derive the scattering and absorption coefficients, as well as the mean cosine of the scattering angle. The results indicate that scatter exceeds absorption by at least two orders of magnitude. Absorption is most significant at wavelengths below 600 nm. The scattering coefficients lie in the range 30-90 mm-1 at 500 nm, and fall smoothly with increasing wavelength to between 10 and 50 mm-1 at 1100 nm. The scattering coefficient for adipose tissue differs, in that it is invariant with wavelength over this spectral range. For all tissues examined, the scattered light is highly forward peaked, with the mean cosine of the scattering angle in the range 0.945-0.985. Systematic differences between the optical properties of some tissue types are demonstrated. PMID- 2236213 TI - Breathing exercises for the medical patient: the art and the science. AB - The art of breathing exercises can be traced to the late 1800s. In the past 10 years, the increased demand for treatment for respiratory muscle failure of dysfunction has resulted in numerous studies evaluating methods of treatment or training. This article provides an overview of research and practice, focused on treating the medical patient experiencing dyspnea or loss of respiratory muscle strength and endurance. PMID- 2236212 TI - Relationship between trunk muscle torque and bone mineral content of the lumbar spine and hip in healthy postmenopausal women. AB - The purpose of the study was to determine the relationship between trunk muscle strength and bone mineral density (BMD). Fifty-six postmenopausal women, aged 38 to 73 years, were examined. The BMD of lumbar vertebrae L2-4, the femoral neck, the Ward's triangle, and the greater trochanter was measured with dual-photon absorptiometry. Isometric and isokinetic torque and work measurements obtained on a trunk testing unit were used to assess trunk flexor and extensor strength. Correlation analysis demonstrated a statistically significant relationship between most trunk torque and work measurements and BMD. The trunk extensors generally provided higher correlations with BMD than did the trunk flexors, and the isokinetic extension torque values demonstrated higher correlations than the isometric extension values in every case. Linear backward-regression models, based on the subjects' weight and trunk flexor and extensor torque and work measurements, demonstrated multiple-correlation coefficients of .67, .58, .43, and .65 in predicting the BMD of the L2-4 region, femoral neck, Ward's triangle, and greater trochanter region, respectively. Estrogen therapy status did not affect the linear regression models. These data suggest a positive relationship in postmenopausal women between flexor and extensor torque values and BMD at the lower lumbar spine and proximal femur. PMID- 2236214 TI - What is empathy, and can empathy be taught? AB - Empathy is a commonly used, but poorly understood, concept. It is often confused with related concepts such as sympathy, pity, identification, and self transposal. The purposes of this article are to clearly distinguish empathy from related terms and to suggest that the act of empathizing cannot be taught. According to Edith Stein, a German phenomenologist, empathy can be facilitated. It also can be interrupted and blocked, but it cannot be forced to occur. What makes empathy unique, according to Stein, is that it happens to us; it is indirectly given to us, "nonprimordially." When empathy occurs, we find ourselves experiencing it, rather than directly causing it to happen. This is the characteristic that makes the act of empathy unteachable. Instead, promoting attitudes and behaviors such as self-awareness, nonjudgmental positive regard for others, good listening skills, and self-confidence are suggested as important in the development of clinicians who will demonstrate an empathic willingness. PMID- 2236215 TI - Effects of electromyographic processing methods on computer-averaged surface electromyographic profiles for the gluteus medius muscle. AB - The objective of this study was to demonstrate how two different linear envelope detectors, as used in the quantification of surface electromyographic (EMG) signals, can lead to differences in the properties of observed computer-averaged EMG profiles. Eight healthy male subjects, aged 24 to 32 years, participated in the study. Computer-averaged EMG profiles for the gluteus medius muscle were recorded at a free-walking cadence and at stepping frequencies of 78 and 120 steps/min, using detectors with 3- and 25-Hz cutoff frequencies simultaneously. The 3-Hz filtered EMG profiles proved to be smoother, to exhibit a significantly lower cycle-to-cycle variability, and to have a greater time lag with respect to the original unprocessed EMG signal than the 25-Hz filtered EMG profiles. The observed intersubject variability also was lower for the 3-Hz filtered EMG profiles than for the 25-Hz filtered EMG profiles. The results indicate that comparison of EMG profiles recorded with different detectors is difficult. A standard detector may solve this difficulty. PMID- 2236216 TI - Twenty-Fourth Mary McMillan lecture. Camelot revisited: legacy of the physical therapy education program at Case Western Reserve University. PMID- 2236217 TI - A new single-stage step test for the clinical assessment of maximal oxygen consumption. AB - Assessments of cardiorespiratory fitness are important in any health-assessment program or routine involving variables that may be influenced by an individual's level of physical fitness or ability to sustain an exercise program. Recently, a new single-stage step test was introduced that uses a height-adjustable platform to normalize the height of stepping for individuals of varying stature. This computer program is designed to simplify the use of this test and to facilitate the implementation in clinical environments where equipment or time is limited, yet accuracy and validity are essential. PMID- 2236218 TI - Stimulating clinical research. PMID- 2236219 TI - Movement science and its relevance to physical therapy. PMID- 2236220 TI - A dynamical systems approach to motor development. AB - The study of motor development has long influenced the clinical practice of physical therapy. We first review the contributions and deficiencies of two traditional maturational and reflex-based models of motor development. Second, we describe basic principles of kinematic and kinetic analyses of movement and show how we have applied these techniques to understand infant stepping and kicking. Third, we propose a theory of motor development based on a dynamical systems perspective that is consistent with our infant studies. Finally, we explore the implications of the model for physical therapists. PMID- 2236221 TI - Animal models offer the opportunity to acquire a new perspective on motor development. AB - During much of this century, our views of motor development were greatly influenced by speculations as to the role of reflexes in the control of movement. However, recent work casts a new view regarding the organization and control of movement. In this article, a review of recent studies of motor development in neonatal kittens and chick embryos is provided. The results of these studies suggest that very early in development there is considerable potential for coordinated movement. The potential for coordinated movement may also exist in early human development. Whether coordinated movement is observed appears to be dependent on a number of variables. For example, mechanical factors emerging during movement may impose demands that restrict the expression of coordinated movement. One possible implication for the practice of physical therapy is that researchers and clinicians will need to precisely characterize and quantify movement variables to advance our knowledge of the processes driving development and to establish effective means for addressing the movement problems of a pediatric population. PMID- 2236222 TI - Life-span development in functional tasks. AB - A life-span concept of motor development is presented as a framework for interpretation of a series of studies of righting tasks. Beginning with the task of rising from the floor, the use of a component approach for movement pattern description and for the identification of developmental sequences of motor patterns is reviewed. Studies applying this approach to a wide range of age groups and to various functional righting tasks are discussed. Recent studies investigating factors related to movement patterns used to perform one of the righting tasks are also reviewed. Suggestions concerning the ways in which this information could be applied to physical therapy practice are included. PMID- 2236224 TI - Motivational considerations in physical activity involvement. AB - The purpose of this article is to examine movement science research on personal and social-environmental motivational influences in physical activity contexts. Motivation is defined as a process in which internal and external factors direct and energize thoughts, feelings, and actions. Motivation is described as a consequence of meaning, which is derived from a combination of personal and social factors, including personal goals or incentives, expectations of personal efficacy, movement-related perceptual and affective experiences, and social and physical features of the environment. Recent literature from sport and exercise psychology is presented on these variables, their determinants, and their consequences for choice, effort, persistence, and performance behavior in exercise and sport contexts. PMID- 2236223 TI - Changes in posture control across the life span--a systems approach. AB - In this article, a systems approach to the development of posture control across the life span and its integration with voluntary tasks such as walking is described. Research shows a clear cephalocaudal gradient in the development of postural responses. Postural muscle synergies develop appropriate temporal organization through experience in each new level of postural skill development. Sensory inputs contributing to posture control influence postural responses very early in development, with responses being elicited by vision alone, or by somatosensory and vestibular cues in isolation. Studies of older adults indicate small, but significant, increases in onset latencies and disruptions in the temporal organization of postural muscle responses when subjects are given external threats to balance. In addition, older adults, like young children, use antagonist muscles more often in coactivation with agonist muscles. Older adults also have more difficulty balancing when sensory inputs are reduced experimentally or pathologically. Ankle dorsiflexor muscle weakness is also a factor in balance dysfunction in the older adult. PMID- 2236226 TI - Dynamic pattern theory--some implications for therapeutics. AB - This article introduces the Dynamic Pattern Theory of movement coordination and discusses possible implications of the theory for therapy. Basic constructs such as order parameters and control parameters, fluctuations, time-scale relations, and self-organization are discussed. Emphasis is given to their potential use to assess the coordination of functional motor acts. The theory's predictions about how motor acts are organized and the implications of its tenets for motor learning and the recovery of motor function are described briefly. A number of implications derived from the theory may support treatment strategies already in place and provide new insights for the future development of such strategies. PMID- 2236225 TI - Information processing for motor performance in aging adults. AB - Movement control systems are altered by the aging process. A growing body of research exists that explains the known changes that occur with aging, and many of those changes are related to central nervous system (CNS) effects. This article reviews motor control and learning issues related to CNS information processing effects of aging and the effects of practice and physical conditioning on reactive capacity. The extensive variability in motor-performance abilities of older people is addressed, and the significance of individual differences is emphasized. PMID- 2236227 TI - Controlling stability of a complex movement system. AB - Human movement systems have frequently been treated as one-dimensional, single axis, rigid bodies in order to simplify the gathering, analysis, and interpretation of data. The problem with this approach is that the results of such assumptions often lead to conclusions about the production and control of movement that do not relate to the control demands placed on the central nervous system. In order to truly understand how the central nervous system plans and produces movements to match environmental demands, we must take into account the many variations available within the body. The purpose of this article is to examine two movement systems that have the potential to act in multiple spatial dimensions with variable muscle action patterns when performing a stabilizing task. Methods of analyzing how the systems operate under differing task constraints and results of the experiments will be presented. Hypothetical models that have been proposed to explain how complex movement systems operate will also be discussed. PMID- 2236228 TI - Coordination of posture and movement. AB - Movement is performed against a background of subtle postural adjustments that counteract destabilizing forces imposed by the movement. Despite the importance of these postural adjustments to the safe and efficient performance of movement, little is known about the properties of these postural accompaniments. The purpose of this article is twofold. First, it provides a review of properties of postural adjustments that accompany a variety of limb and trunk movements. Second, a schema for the coordination of posture and movement is proposed. This schema suggests that a central nervous system model of body dynamics is essential to anticipatory control of posture during movement. PMID- 2236229 TI - Sensorimotor contributions of the basal ganglia: recent advances. AB - In the last decade, a great deal of research has been aimed at ascertaining the manner in which the basal ganglia (BG) contribute to the control of movement. The formation of workable hypotheses, however, has been limited by the great variety of putative roles reported in the literature. Reported functions have often been in direct conflict. Recent developments, however, provide new perspectives from which to view seemingly discordant functions. Data reviewed in this article suggest a distinct anatomical topography within the BG, allowing for highly specialized subfunctions. In parallel, BG cellular activity has been found primarily in association with specific sensory and task-related dimensions relevant to particular movements. The multiple sensorimotor contributions of the BG therefore are not contradictory, but represent BG contributions within different functional contexts. These multiple roles of the BG offer particular clinical insights. PMID- 2236230 TI - [Digital subtraction varicography]. PMID- 2236231 TI - [Dynamic model of the calf muscular pump]. PMID- 2236232 TI - [Rehabilitation in peripheral vascular pathology]. PMID- 2236233 TI - [Repercussions of venous diseases on the osteoarticular system of the lower extremities]. AB - Two centuries ago, a leading light of phlebology (J.-L. Petit) wrote, "When ulcers, located beside bones, have been present for more than one year, the bones rot". Today, on the basis of many anatomical and radiological studies, this statement can be modified as follows: bone lesions may occur even before the onset of an ulcer; their nature is very variable and they are certainly more extensive in long-standing phlebopathies. In legs presenting open ulcers for more than 5 years, bone lesions are nearly always present but may not coincide with the location of the ulcer; the changes occur in the same way and follow the same pattern in post-phlebitic ulcer and in essential varices. Within the legs, notable reciprocal potentially pathogenic relationships are set up between the joints and the veins. These are more marked in the distal section of the limb than in the proximal section. It is therefore essential that at the first phlebological consultation, particularly in the presence of serious cutaneous lesions, an in-depth investigation should be carried out of the functional state of the osteoarticular system in order to be able to combine treatment of the venous pathology with a correct restoration of the hemokinetic pump. PMID- 2236234 TI - [Pneumatic pressure therapy of lymphedema in the lower limbs]. PMID- 2236235 TI - [Venous pathology]. PMID- 2236236 TI - [Arterial pathology]. PMID- 2236238 TI - [Investigations of function]. PMID- 2236237 TI - [Lymphatic pathology]. PMID- 2236240 TI - [Treatment of foot varices by ambulatory phlebectomy]. PMID- 2236241 TI - [Doppler echography of the popliteal fossa and the calf, prior to ambulatory phlebectomy]. PMID- 2236242 TI - [Venous endoscopy and ambulatory phlebectomy]. PMID- 2236239 TI - [Local anesthesia in ambulatory phlebectomy by the method of R. Muller: risk assessment by lidocaine dosage]. AB - Local anesthesia for ambulatory phlebectomy makes it necessary to inject a considerable quantity of lidocaine. This study involved 50 operations. The doses of lidocaine containing 1% adrenaline and injected after cooling (between 2 and 5 degrees C) ranged from 200 mg to nearly 900 mg in a single administration. The assays of lidocaine in the peripheral venous blood were carried out by means of F.P.I.A. (Fluorescence Polarization Immuno Assay) at times 0, 30 min 60 min, 90 min., 24 hours and 48 hours. The peak concentration obtained (1.8 micrograms/ml) for a dose of 700 mg in a subject weighting 65 kg, i.e. 10.9 mg/kg, was only one half the concentration considered to be neurologically toxic (4 to 12 micrograms/ml) or one-twelfth of the toxic levels with regard to the cardiovascular system (24 micrograms/ml). The performance of local anesthesia in the physician's office is devoid of major risks, even though the doses used during AP are much higher than those usually administered in routine dematological surgery. PMID- 2236244 TI - [Personal experience with cryosurgery in varices]. PMID- 2236243 TI - [The external pudendal veins. An anatomo-clinical study, their treatment by ambulatory phlebectomy (Muller method)]. AB - Forty-one cases of E.P. varices (bilateral in 3 cases) were identified after examining 1371 patient histories followed up between 1985 and 1989 inclusive, i.e., 2.99 percent. Analysis of the history, clinical signs and Doppler and arguments based on the practice of ambulatory phlebectomy of the thighs made it possible to establish an accurate anatomical description of these somewhat poorly understood venous territories: simple or complex origin, principal or secondary saphenous ending and non-saphenous endings, supramelic, para-public, labial and perineal connections, extensions into other territories, defining major EP varicoses. Physical-pathological investigation can establish the frequently autonomous nature of these EP varicoses. The high incidence of primary reflux, their wide distribution along the varicose axes prolonged over 1 to 3 segments of the limbs, characterize the 37 cases of major EP varicosis. Therapeutic analysis reveals: the inadequacy of surgery and sclerosis in severe cases, the efficacy of ambulatory phlebectomy (A.P.) AP presents specific characteristics of method and bandaging related to the quality of the skin and venous tissue and the EP site. Thirty APs were carried out with very good anatomical, functional and aesthetic results. PMID- 2236245 TI - [The value of velocimetric investigation of the uterine arteries in retro placental hematoma. 3 cases]. AB - Retro-placental hematoma is a sudden event with a serious prognosis which is aggravated by the very frequent absence of premonitory clinical, biological or ultrasonic signs. Does a velocimetric investigation of the uterine arteries have any predictive value in this disorder? The apparatus used was a continuous Doppler with spectral analysis and a 4 MHz probe no ultrasonic location. Each examination involved the exploration of 2 uterine arteries and of the umbilical flow. The method of recording the uterine arteries is described. Three cases of retro-placental hematoma are reported. In these three cases, an increase in the resistance index of one of the uterine arteries (the right artery in 2 cases and the left in 1 case) was detected with the presence of a protodiastolic notch on the trace, whereas the umbilical index itself was normal and no other sign was present which could predict the placental event. The value of the Doppler recording is already established in many obstetric indications, and these should be extended yet further, particularly if this preliminary study is confirmed on a larger scale. PMID- 2236247 TI - [Recommendations for standardizing the vocabulary and evaluation criteria in venous pathology (2nd part)]. PMID- 2236246 TI - [Behavior of human endothelial cells in hyperoxia and hypoxia: effect of Ginkor Fort]. AB - Recent discoveries have shown that venous diseases have a multifactorial etiology. One of the factors which is definitely involved in this pathologic process is the change in the concentration of oxygen. An increase in the concentration of oxygen, hyperoxia, or reoxygenation following hypoxia, damages the tissues by stepping up the production of free radicals. In addition, a reduction in oxygen concentration, or hypoxia, is also damaging, probably through a reduction in ATP synthesis. From a therapeutic standpoint, the veins, and more particularly the endothelium, must be protected against the impact on the tissue of these changes in oxygen concentration. In this study, the effects of Ginkor Fort were tested on cultured endothelial cells subjected to varying oxygen pressures. The results show that Ginkor Fort can provide good protection of endothelial cells against hyperoxia and hypoxia-reoxygenation. These beneficial effects are probably due to the presence of flavonoids in the Ginko biloba extract; these flavonoids have an anti-oxidant effect. In addition, this substance also protects the cells against hypoxia, possibly by increasing the availability of oxygen for ATP synthesis. This dual protective effect, which is produced by two different mechanisms, may account for the wide spectrum of Ginkor Fort in its use in venous diseases. PMID- 2236248 TI - In search of physiological principles: the use of animal diversity and novel technology. APS Specialty Meeting. Orlando, Florida, October 6-10, 1990. Abstracts. PMID- 2236249 TI - Role of integrative physiology in research programs of modern physiology departments. PMID- 2236250 TI - Minority recruitment physiology instruction on the Crow Indian Reservation. PMID- 2236251 TI - Salvation--it's just around the corner! PMID- 2236252 TI - Physiology in a South African homeland. PMID- 2236253 TI - Eric Liljencrantz Award. PMID- 2236254 TI - Effects of regional amygdaloid lesions on flight and defensive behaviors of wild black rats (Rattus rattus). AB - Flight and defensive behaviors of wild black rats (R. rattus) in response to nonpainful threatening stimuli were examined before and after regional amygdaloid lesions. Striking disruption of flight was found following damage to all major amygdaloid regions. In contrast, reduced defensiveness was most consistently associated with damage to cortical and, perhaps, central nuclei. The diffuse organization of flight behavior may result from extensive modality-specific cortical afferents to the amygdala and the varied provided by naturalistics threats. The more restricted representation of defensive attack may have resulted from diminished responsiveness to vibrissal stimulation mediated by medial and dorsomedial amygdaloid structures. PMID- 2236255 TI - The influence of maternal labels on dietary preferences of spiny mouse weanlings. AB - To assess the influence of conspecific chemical cues on the development of dietary preferences, spiny mouse (Acomys cahirinus) weanling were tested for their responses to food items that were partially eaten (thus, presumably labeled) by various categories of conspecifics. Consumption of a highly preferred novel food (fresh carrot) labeled by the pups' parents, or mother alone, was greater than that of a clean sample of the same food. The presence of labels emanating from the father or an alien mother had no effect on food consumption. Salient maternal labels that elicit preferential feeding by young appear to be individually unique, therefore allowing pups to recognize such cues emanating from their own mother. The attractive substance that mothers transfer to food items while eating (the maternal label per se) has not been identified, but saliva is a likely candidate. PMID- 2236256 TI - Brain structures important for solving a sawdust-digging problem in the rat. AB - Young rats subjected to bilateral lesions to one of 37 different brain sites were initially trained to traverse a narrow runway to reach a goal box containing water. The test involved blocking a portion of the runway with sawdust and determining whether the animals would burrow through the sawdust to gain access to the goal box. Lesions to 30 brain sites produced deficient performance on the sawdust-digging problem. This study, combined with earlier investigation of 11 additional brain sites, shows that 41 of 48 total brain sites are involved in this task. These findings suggest that underlying brain mechanisms include a nonspecific mechanism and several specific mechanisms, such as visuospatial attentional, visual discrimination, vestibular-proprioceptive-kinesthetic discrimination, response flexibility, but much less place learning mechanisms. PMID- 2236257 TI - Learning and rhythmic human EMG in ecological perspective. AB - Previous evidence of strong interactions between learning and human treadmill locomotion led to a simplified system for studying learned rhythms in a framework of behavioral ecology. Motor control combined with instrumental conditioning in a rhythmic hand task with repeating trials, blocks, and complete regimens. Regimen contexts differed with respect to the pattern of stimulation before and after an electromyographic (EMG) response. Both an antecedent stimulus (a light flash) and a consequent stimulus (a tone indicating success or failure) were necessary for conditioning. Arguments were given for defining reinforcement as a composite of interdependent and size-scaled processes, some including knowledge of results, instead of as a single event after a response. PMID- 2236258 TI - Sleep and EEG spectra in the rabbit under baseline conditions and following sleep deprivation. AB - The 24-hr sleep-wake distribution and power spectra of the electroencephalogram were determined in rabbits that had been implanted with cortical and hippocampal electrodes. A diurnal preference for sleep was observed. The spectral power density in nonrapid eye movement sleep (NREM sleep) of the cortex showed a decreasing trend in most frequencies within the 12-hr light period. In the 12-hr dim period no clear trend was present. Most hippocampal EEG frequencies decreased in NREM sleep in the first two hours of the light period, and thereafter stayed on a constant level. Sleep deprivation elicited the following changes: a prolonged increase of NREM sleep and a short increase of REM sleep; in the cortex, an increase of slow-wave activity (SWA; power density in the 0.25-2.0 Hz frequency band) in NREM sleep, which declined in the course of recovery; an enhancement of slow-wave (1.25-3 Hz) and theta (6.25-7 Hz) activity in REM sleep. The hippocampus showed an increase in NREM sleep power density in almost all frequencies. In REM sleep the hippocampus exhibited an increase in power density in the 6.25-7 Hz and 12.25-13 Hz bands, whereas in the 7.25-8 Hz band the values were below baseline. The results show that SWA in NREM sleep and theta activity in REM sleep are enhanced by sleep deprivation, as has been observed in other mammalian species. The EEG changes in the hippocampus resembled those in the cortex. PMID- 2236259 TI - Startle-inducing acoustic stimuli evoke ultrasonic vocalization in the rat. AB - The present study demonstrates that acoustic stimuli which induce a startle response (ASR) also evoke ultrasonic vocalization in the rat. Sound recordings were done on three consecutive days of testing during sessions of 20 acoustic stimuli each and on the following day for three minutes following 5 acoustic stimuli (nonstimulus condition). Startle-inducing stimuli evoked continuous ultrasonic calling which was maintained throughout testing. Immediately following each acoustic stimulus, however, vocalization was interrupted by a period of silence (gap). The mean duration of sounds was reduced and the interpulse interval tended to increase during acoustic stimulation as compared to the nonstimulus condition. It is concluded that startle-eliciting stimuli induce a state of fear in the rat and that the acoustic-startle-elicited ultrasonic vocalization may provide a novel model in the study of anxiety. PMID- 2236260 TI - Differential effects of colchicine lesions of dentate granule cells on wet dog shakes and seizures elicited by direct hippocampal stimulation. AB - Direct electrical stimulation of either the dorsal or ventral hippocampal formation elicits wet dog shakes and overt seizures. Destruction of dentate granule cells in the dorsal hippocampal formation does not significantly reduce the number of wet dog shakes elicited by ventral hippocampal stimulation. However, destruction of dentate granule cells in the ventral hippocampus virtually eliminates wet dog shaking elicited by dorsal hippocampal stimulation. Destruction of either dorsal or ventral dentate granule cells lowers the threshold for eliciting forelimb clonus with rearing. These results suggest that dentate granule cells in the ventral hippocampus are essential for wet dog shakes elicited by intrahippocampal stimulation. However, dentate granule cells throughout the hippocampal formation appear to play an important inhibitory role in the spread of seizure activity within the hippocampus. PMID- 2236261 TI - Glycolysis in Anolis carolinensis during agonistic encounters. AB - We examined the influences of territorial status, encounter outcome, body mass difference, activity, and display on lactate accumulation in adult male Anolis carolinensis during agonistic interactions. Of the pairs of lizards frozen at the onset of an encounter, intruders had significantly higher lactate concentrations than residents. Lactate levels at the onset of an interaction were not significantly different from those at the conclusion, suggesting a limited role for glycolysis during such events. The outcome of an agonistic encounter was not based on fatigue. Individuals that were larger or changed sites had a lower relative lactate concentration at the conclusion of an interaction than smaller or sedentary animals. We consider the influence of autonomic arousal on glycolysis. PMID- 2236262 TI - Circadian rhythmicity and behavioral depression: I. Effects of stress. AB - Rats were exposed to repeated sessions of inescapable footshock, and behavioral depression was subsequently assessed by measuring escape performance during exposure to escapable shock in a different testing environment. Free-running circadian activity rhythms were assessed using running wheels for approximately three weeks before and after administration of inescapable shock. Several animals showed lengthening of free-running period and decreases in activity level following shock. Similar effects were also seen in rats that were removed from their running wheels, placed within the shock apparatus, and not given shock, but not in nonhandled control animals. Furthermore, period lengthening in shocked and handled rats was positively correlated with escape performance, suggesting that circadian rhythm alterations occurred in those animals that were best able to cope with shock or handling-related stressors. In contrast, individual differences in circadian period and activity level during baseline conditions were not predictive of either escape performance or circadian rhythm alterations. These results suggest that successful behavioral adaptation to stress may be associated with alterations of circadian rhythmicity. PMID- 2236263 TI - Circadian rhythmicity and behavioral depression: II. Effects of lighting schedules. AB - Two studies explore the relationship between rhythmicity and behavioral depression. Behavioral depression was induced using inescapable footshock, and assessed by measuring subsequent responses to escapable shock, in rats housed under different light-dark conditions. Experiment 1 compared escape performance in free-running and entrained animals following inescapable shock. Free-running and entrained animals did not exhibit differential vulnerability to the effects of inescapable shock. In addition, there were no systematic effects on phase following shock. However, several free-running animals showed increased circadian period following shock, and lengthening of period was significantly correlated with escape performance. Individual differences in baseline period or phase were not predictive of escape performance. In Experiment 2, "aftereffects" of entrainment to long or short light-dark cycles were utilized to create groups of animals with long or short free-running periods. After the administration of inescapable shock, escape performance was tested. There were no significant differences among experimental groups in escape performance. These results suggest that plasticity of circadian period, but not baseline period per se, may be associated with the ability to adapt to environmental challenges. PMID- 2236264 TI - Thyroparathyroidectomy produces a progressive escape deficit in rats. AB - Abnormal thyroid status and affective disorders have been associated in the human clinical literature. It has recently been shown that pretreatment with thyroid hormone can prevent escape deficits produced by inescapable shock in an animal analogue of depression. In this report we provide evidence that hypothyroid status can produce an escape deficit in rats. While sham-operated rats improved their performance on a simple escape task over three days of testing, thyroparathyroidectomized rats showed a pronounced decrease in their responses. Markov transition analysis was used to obtain conditional probabilities of escaping given a prior escape or failure to escape for the two groups. This analysis shows that the structure of the data set may be similar for the two groups. These results suggest that if intact rats learn to escape, then hypothyroid rats may learn not to escape. PMID- 2236265 TI - Habituation of the galvanic skin response in adult males as a function of age. AB - Habituation of the galvanic skin response (GSR) to electric shock was studied in 28 male college students, 18-39 years old. A 60-Hz shock of 244.0-msec duration was presented every 1-3 min above the right ankle in a preprogrammed sequence. The GSR, measured as a change in palmar skin conductance to the shock, was examined over the first 17 shock trials. The habituation curve showed the typical large decrement over the first few trials followed by a smaller one over several more trials. The initial rate of habituation (percent decrement between shock trials 1 and 3) was shown to be age related even though none of the subjects would be considered old (18-39 years old). The younger the subject, the faster the initial habituation or, conversely, the older the subject the slower the rate (rs = -.50, N = 28, p less than 0.005). The asymptote did not vary with age. That such dramatic changes occur in the CNS of young males over a relatively few years is not unknown. PET studies of the caudate nucleus in normal males showed an exponential decrease in dopamine receptors with about half of the decrease occurring rapidly between the ages of 20 and 30 (Wagner, H.N., Jr. Diag. Imaging Nov.: 138-145; 1985). The usefulness of the GSR in detecting age effects in other kinds of learning, such as Pavlovian conditioning, is being explored, as well as its usefulness in detecting early learning/memory loss in aging and the dementias. PMID- 2236266 TI - The rat's right-left preference during free exploration of a multiple Y-maze. AB - The right-left preference of Wistar, Sprague-Dawley, and Long Evans rats of both sexes was investigated in a multiple Y-maze in which the animals had to perform three consecutive right-left choices in order to go from the common starting point to one of the eight goal arms. The rats were free to explore the maze without being subjected to punishments or rewards. Care was taken to minimize inhibitory influences on exploration (low illumination, no handling to return the rats to home cage). The statistical analysis of the total right-left choices performed by the rats showed that three groups (Wistar females, Sprague-Dawley females, and Long Evans males) exhibited a preference for the right. This preference was not related either to sex or strain, but was possibly a species characteristic. PMID- 2236267 TI - Behavioral effects of chronic imipramine treatment in genetically nervous pointer dogs. AB - The genetically nervous pointer dog has been proposed as a model for human anxiety disorders. In a double-blind placebo-controlled study, seventeen nervous pointer dogs were treated for four weeks with imipramine hydrochloride (10 mg/kg), a potent antipanic agent in humans. Although three of the dogs demonstrated marked improvement to imipramine but not placebo treatment after short-term administration, chronic imipramine failed to modify the aberrant behavior in any of the dogs. These findings are discussed in the context of the nervous pointer dog as a model for human anxiety disorders. PMID- 2236268 TI - Computer analysis of the exploratory behavior of insects and mites in an olfactometer. AB - A method of quantification of the exploratory behavior of small animals stimulated by an odorant in a four-choice olfactometer, taking into account the interindividual variability of responses, was developed: individual tracks were time sampled according to the animal's walking speed and its positions were recorded according to the X-Y coordinates of the grid set underneath the device, the mesh of the grid suiting the animal's body size. A software, written in BASIC APPLESOFT on an APPLE IIe computer, allowed us to analyze the coordinates either of a single individual or of an experimental sample, leading to: a) the quantification of the insect distribution all over the experimental chamber, expressed in a table numbered according to the grid, where the percentage of position per square either for a given time fraction or the total observation period were reported, b) a graphic representation of the data according to several levels of greys, expressing the frequentation for each square for a given duration of observation. An analysis per time fraction allowed the chronological setup of events to appreciate. c) The collection of the positions among each flow field of the olfactometer for each individual of the experimental sample, for a given duration, was translated as the percentage of time spent in each flow field. Data files gathered these percentages for further statistical treatments. This computer method, which requires little equipment and appears to be easily adaptable to the study of biological models of various size and speed such as honeybees, trichogrammas and varroas mites, is a powerful tool for behavioral studies of small organisms tested in restricted areas. PMID- 2236269 TI - Computer-assisted analysis of behavior-brain damage relationships. AB - Experimental destruction of subcortical brain tissue by electrolytic, radio frequency, or excitotoxin lesions is commonly used in the study of the neural control of behavior. Relating variability in the locus and extent of brain damage to lesion-produced variability in behavior is essential to a complete analysis of the behavioral effects of brain damage. We describe the use of commercially available computer accessories and software for measuring the area of irregular polygons to accurately and rapidly estimate the amount of damage to any of a number of brain structures included within an area of experimental destruction. We then describe the use of statistical programs for correlation and multiple regression in calculating relationships between damage to particular structures and behavior. As an example, we show that excitotoxin (and presumably axon sparing) lesions of lateral hypothalamic tissue adjacent to the caudal zona incerta virtually eliminate male sexual behavior in rats. The use of multiple regression analysis, in conjunction with procedures for calculating destruction to different brain regions, provides a way of correlating brain damage and behavior that has widespread application in studies of the behavioral effects of brain lesions. PMID- 2236270 TI - Effects of drinks sweetened with sucrose or aspartame on hunger, thirst and food intake in men. AB - Forty-two nondieting adult males were given 8 or 16 oz of lemonade, sweetened to equal intensity with either aspartame or sucrose, or the same volumes of water, or no drink. Subjects were separated into three groups receiving the drinks at different times: with a self-selection lunch, or 30, or 60 min before lunch. Food intakes did not differ when subjects received the drinks with lunch; however, when the calories from the drinks were included, intake was significantly greater with the sucrose-sweetened lemonades than in the other conditions. When subjects received the drinks 30 or 60 min before lunch, food intakes were not significantly different. Appetite ratings were not different among the conditions. When the drinks were consumed with the meal, the 8-oz sucrose sweetened lemonade differed from the other drinks in that it did not significantly reduce thirst. The results indicate that in nondieting males, aspartame in concentrations similar to those in commercially available drinks did not increase hunger ratings or food intake. However, caloric drinks taken with lunch increased total energy intake in that meal. Also, sucrose-sweetened drinks may decrease thirst less than water or aspartame-sweetened drinks when taken with a meal. PMID- 2236271 TI - Anodal polarization in the substantia nigra increases rotational behavior in the rat. AB - Rotational behavior was examined in rats after unilateral application of an anodal direct current (3 microA, 30 min) to the substantia nigra pars compacta (SNC). The current application increased contralateral rotation in two stages. One was during the period immediately after the current application, in which the increase in rotation declined within 30 min. The other period was long lasting, in which rotation increased 2 hr after the application and persisted for 24 hr or more. These results suggest that anodal direct currents induce transient and long lasting activation of the SNC neurons, resulting in increases in rotational behavior. PMID- 2236272 TI - Experimental dissociation of behavioral and cardiovascular outcome in the borderline hypertensive rat. AB - F1 Offspring of hypertensive and normotensive rats (BHR) were reared with either hypertensive (SHR) or normotensive (WKY) cagemates, and observations were conducted at two developmental periods to assess the effects of rearing condition on the social environment and the behavior of BHR subjects. SHR displayed significantly more agonistic behavior during development than WKY, and BHR subjects reared with SHR were the targets of significantly more agonistic behavior than BHR subjects reared with WKY cagemates. BHR reared with SHR initiated twice as much agonistic behavior as BHR reared with WKY. When heart rate and blood pressure were assessed at 75-80 days of age, however, neither the alterations in developmental social environment nor the alterations in the behavioral characteristics of BHR were associated with differences in cardiovascular variables. The results do not support a causal connection between behavioral characteristics and cardiovascular outcome. PMID- 2236273 TI - A simple technique for localizing the primary auditory cortex in the rat. AB - A technique is described which will identify the skull position which directly overlies the sensory receiving area of the auditory cortex in the rat. This allows the recording of primary cortical auditory-evoked potentials with a high rate of success. PMID- 2236274 TI - Haloperidol-induced disruption of retrieval behavior and reversal with apomorphine in lactating rats. AB - Lactating rats were used in experiments to examine the role of the dopamine system in the regulation of ongoing maternal behavior. Administration of haloperidol disrupted retrieval behavior and nest building in a dose-dependent manner but not nursing behavior and pup licking. Feeding behavior including carrying of food pellets to the nest and general locomotor ability were not disrupted by haloperidol. Apomorphine effectively reversed the inhibition caused by dopaminergic blockade. These results indicate a role for dopamine in the motivational regulation of retrieval and nest building during the postpartum phase of maternal behavior. PMID- 2236275 TI - An open-field activity analysis of labyrinthectomized rats. AB - A detailed behavioral analysis was performed on rats that received bilateral labyrinthectomies. They were placed in a walled activity monitor (39 x 39 cm) that allowed the animal to move freely within the enclosure. Their behavioral activities were automatically recorded. These activities were placed into twelve different categories. The results show a lower rate of habituation for the labyrinthectomized animal as well as an overall increase in activity over all dimensions as compared to the control. This increase in behavior may be exploratory and a necessary feature in the formation of spatial maps. PMID- 2236276 TI - Rats with one olfactory bulb removed and the contralateral naris closed can detect odors. AB - Rats with one olfactory bulb removed were trained to detect 0.5%-0.005% concentrations of amyl acetate. These rats had only a slight decrement in performance when the naris ipsilateral to the intact olfactory bulb was closed. Thus, vapors inhaled through one naris can stimulate olfactory receptor neurons in the contralateral nasal vault. This internasal stimulation is probably mediated by the nasopharyngeal canal or nasopharynx. PMID- 2236277 TI - Gait topography in rat locomotion. AB - Gait topography has been quantified and normative data established for free, spontaneous locomotion in rats. The normal walking pattern has been compared for male and female rats and for three rat strains. The normal walking gait was found to be symmetrical, and measures of stride width (SW) and stride length (SL) were consistent, with coefficients of variability ranging between 10 and 21%. A study of gait ontogeny found that for both male and female rats, SL increased as a linear function of body weight, whereas SW increased curvilinearly. The results indicate that repeated measures of gait topography were not subject to interference from habituation. A sex difference in gait ontogeny was observed. The developmental pattern is similar for both sexes, but males increase both SL and SW faster than females. It is proposed that gait topography may yield valuable information in activity studies. PMID- 2236278 TI - Meal patterns of pygmy goats fed hay and concentrate ad lib. AB - The meal patterns of pygmy goats fed hay and pelleted concentrate ad lib were recorded and analyzed. The pygmy goats consumed 8 hay meals [6 during the light phase (= light)/2 during the dark phase (= dark)] and 10 concentrate meals (7 during light/3 during dark) during 24 hr (12 hr light/12 hr dark). Sixty-two percent of hay and 74% of concentrate intake occurred during light. Total 24-hr hay (280 g) and concentrate (264 g) intakes were similar, but concentrate was preferred during dark. Concentrate meals were smaller during light than during dark. The mean feeding rate (g/min) within meals for both hay and concentrate was higher during dark than during light. Meal size and duration of postmeal interval were positively correlated for concentrate but not for hay. No significant positive correlation was found between meal size and duration of premeal interval. Separate analysis of diurnal and nocturnal meals indicated that the postmeal correlation for concentrate was evident primarily during dark. The results demonstrate that food intake in pygmy goats shows distinct diurnal variations and suggest that food intake in ruminants is regulated from meal to meal, with different factors prevailing during light and dark. PMID- 2236279 TI - Perinatal decortication impairs performance on an 8-arm radial maze task. AB - Two experiments evaluate the role of the neocortex in rodent spatial learning. In Experiment 1, perinatally decorticated rats and sham-operated controls began ten training sessions at day 200 on an 8-arm radial maze. Decorticated rats made more errors than controls, but showed improvement by the tenth session. In the second experiment, training was extended to determine whether decorticates could eventually match control performance levels if given sufficient training. Spontaneous activity levels were also recorded and compared to maze performance to investigate the relationship between poor performance on the radial maze and activity. More than half of the decorticates reached criterion performance. Decorticates had significantly elevated spontaneous activity levels when compared to controls, and the magnitude of this hyperactivity was related to performance deficits on the radial maze. These results suggest that with extended training decorticates can learn a spatial task. Performance deficits may reflect the hyperactive tendency of decorticates rather than a specific impairment of spatial learning abilities. PMID- 2236280 TI - Developmental changes in sugar and starch taste preferences in young rats. AB - Recent studies indicate that neonatal and adult rats are attracted to the taste of sugar as well as to starch-derived polysaccharides (e.g., Polycose). The present study investigated whether the relative preference for sweet and starchy tastes changes during the postweaning to adulthood period in male and female rats. This was accomplished by giving growing rats 24-hr/day one-solution (sucrose or Polycose vs. water) and two-solution (sucrose vs. Polycose) preference tests over a 9-week period (from 28 to 98 days of age). Acceptance (absolute intake) of sucrose and Polycose was also evaluated by comparing solution intakes during one-solution tests with water baseline intakes. Dilute solutions were used to minimize postingestive caloric and/or colligative effects. When tested with 2% saccharide solutions, the rats strongly preferred sucrose to Polycose with the preference increasing in magnitude from weeks 1 to 9 of testing. Sucrose acceptance also increased, relative to that of Polycose, after the third test week. When tested with 0.06 molar solutions, the rats initially consumed more Polycose (week 1) but by the fifth test week their sucrose preference and acceptance exceeded that of Polycose. These results indicate that the preference for sweet taste, relative to that for starchy taste, increases with age. Contrary to previous findings, the sweet taste preference was somewhat stronger in the male rats than in the female rats. PMID- 2236281 TI - High-fat diet preference in developing and adult rats. AB - Diet preference tests in rats have yielded equivocal results, as some investigators have reported a strong preference for diets high in fat over those containing less fat, while others have failed to see this preference. To further explore this unresolved problem, two diet preference experiments were conducted. In Experiment 1, adult rats were maintained for at least three months on one of three powdered diets (control, high-carbohydrate or high-fat). Rats were then given a preference test with all three diets available. Animals from each group overwhelmingly preferred the high-fat diet. To determine whether this preference was also present in younger, developing rats, in Experiment 2, weanling animals were tested with the same three diets as in Experiment 1. As observed with adult animals, weanling rats also showed a strong preference for the high-fat diet. The idea that rats prefer a diet with a relatively high level of fat is supported. Possible explanations for these findings are discussed. PMID- 2236282 TI - Salivary testosterone measurements: reliability across hours, days, and weeks. AB - Salivary testosterone measurements would appear to be useful in behavioral research, where subjects are often reluctant to provide serum samples. The usefulness of salivary measurements depends upon their reliability, however, which was the focus of the present investigation. In four studies, 270 male and 175 female subjects collected saliva samples at times ranging from 30 min to 8 weeks apart. Subjects collected samples on at least two days, at time of awakening, midmorning, late afternoon, and late evening. Mean testosterone concentration dropped about 50% from morning to evening for both sexes, with largest drops early in the day. Mean reliability was r = .64 across two days and r = .52 across seven-eight weeks. Menstrual cycle effects were negligible. Reliability can be increased by using more than one measurement, and it is probably desirable to combine measurements taken several weeks apart. Salivary assays offer a practical way of measuring testosterone in free-ranging subjects outside the laboratory. PMID- 2236283 TI - Responsiveness to olfactory stimuli presented in sleep. AB - Whether humans react to olfactory stimuli presented in sleep was assessed. Responses of ten participants (mean age = 22.8 years) were recorded to repeated three-minute periods of either air alone or to a peppermint odor (0.26 mg/liter) during stage 2 sleep. These responses included behavioral (awakening, microswitch closure), autonomic (heart rate, EMG, respiration), and central (EEG) components. An odor delivery system is described comprised of an aquarium pump, Teflon and TYGON tubing, oxygen mask, filtering, and air flow valves. The data indicate that humans react behaviorally, autonomically and centrally to olfactory stimuli presented while sleeping. Although the percentage of overall responsivity to olfactory stimuli was low, significant differences (ANOVA) in responsivity to odor periods vs. nonodor periods were found for microswitch closures, EEG, EMG, and heart rate. For these measures eight or more of the ten participants showed this pattern of differential responsivity during odor and nonodor periods (Sign test = p less than 0.05). A time-of-night effect was also observed in that responsivity tended to be greatest early in the night. The effect on responsivity of other durations, concentrations, and odors requires additional research. PMID- 2236284 TI - Pineal involvement in the alimentary behavior and taste preferences in the rat. AB - The purpose of this experiment was to explore the effects of pinealectomy or sham pinealectomy on circadian rhythms of taste preferences, food and fluid intake and body weight gain in rats. We compared the body weight gain, the amounts of food eaten and that of deionized water, total fluid, salt, sour, sweet and bitter near threshold solutions consumed by rats before all surgical manipulations and after pinealectomy or sham pinealectomy. The results showed that the pineal gland does not exert a major influence on circadian organization of taste preferences, drinking, feeding and body weight modifications in the rat. The failure of pinealectomy to modify light/dark rhythms of taste preferences and other related alimentary behaviors may be explained by the fact that pinealectomy does not completely eliminate circulating melatonin. PMID- 2236285 TI - Recent developments in the biosynthesis of the tropane alkaloids. AB - Recent work on the biosynthesis of the tropane moiety of cocaine, hyoscamine, scopolamine, and related alkaloids is reviewed. Revision of the generally accepted biosynthetic pathway to these alkaloids is now proposed in the light of new discoveries. New information on the biosynthesis of some of the acid moieties (benzoic, tiglic and tropic acid) of the tropane ester alkaloids is also discussed. PMID- 2236286 TI - Gardenia fruit extract stimulates the proliferation of bovine aortic endothelial cells in culture. AB - We previously reported that Gardenia fruit extract had a stimulatory effect on fibrolysis in vitro. In the present study, we describe that the hot water extract from Gardenia fruit (GFE) stimulates the proliferation of cultured endothelial cells from bovine aorta. The cells were cultured in RPMI1640 medium supplemented 10% fetal bovine serum for up to 96 h in the presence of GFE (100 micrograms/ml and below). GFE at 25 and 50 micrograms/ml significantly increased the cell number after 48 h and above of the treatment. The incorporations of [3H]thymidine and [14C]leucine were significantly increased by 50 micrograms/ml GFE. The GFE stimulation of the proliferation was completely inhibited by 1 microM cycloheximide. The stimulatory activity of GFE was recognized in the low relative molecular mass (less than or equal to 10,000) fraction. In conclusion, it was demonstrated that a low molecular mass component of GFE stimulated endothelial cell proliferation and an increased protein synthesis was a essential component of this response. GFE may contain a useful compound to stimulate the proliferation of endothelial cells. PMID- 2236287 TI - Inhibitory effects of saponins from Tetrapleura tetraptera on the LH released by cultured rat pituitary cells. AB - Ethanolic extracts from stem bark of Tetrapleura tetraptera exerted an inhibitory effect on the luteinizing hormone (LH) released by cultured rat pituitary cells. These extracts contained triterpenic saponins, tannins, and flavonoids as estimated through phytochemical screening. Saponins were extracted. They apparently inhibited the luteinizing hormone-releasing hormone (LHRH)-induced LH release, the inhibition level being dose-dependent. Yet, the intracellular LH content remained constant whatever the saponin concentration, which demonstrated a lack of effect on the true release process. Accordingly, an interaction between saponins and LH released into the medium was demonstrated, which led to a decrease in the amount of immunoassayable hormone. This decrease was both time- and dose-dependent. It occurred even in the presence of serum in the medium, which suggests that the inactivation process may occur in vivo. Taken together, these results could explain the anti-gonadotrope properties of T. tetraptera extracts that are used as natural contraceptives in Ivory Coast pharmacopoeia. PMID- 2236288 TI - Growth, terpenoid production and antibacterial activity of an in vitro culture of the liverwort Fossombronia pusilla. AB - In vitro cultures of the liverwort, Fossombronia pusilla, have been ititiated from spores. They grew well on Gamborg B5 medium supplemented with 2% saccharose and 12.5 micrograms/l vitamin B12. Undifferentiated cultures were obtained on Knop mineral solution with 4% glucose. The cultures produced the same constituents as collected material. Perrottetianal A and B, known substances from liverworts were isolated and characterized by spectroscopic methods as well as alpha-(-)-santonin. A hitherto unknown diterpene dialdehyde-8-hydroxy-9 hydroperrottetianal A--could also be characterized. Furthermore, 7 terpenes were identified by GC/MS. A petrol ether extract and the isolated terpenes exerted antibacterial activity. PMID- 2236289 TI - Antimalarial activity of Tanzanian medicinal plants. AB - Tanzanian medicinal plants were extracted and tested for in vitro antimalarial activity, using the multidrug resistant K1 strain of Plasmodium falciparum. Of 49 plants investigated, extracts of three plants were found to have an IC50 between 5-10 micrograms/ml, extracts of 18 other plants showed an IC50 between 10 and 50 micrograms/ml, all others were less active. The three most active extracts were obtained from the tubers of Cyperus rotundus L. (Cyperaceae), the rootbark of Hoslundia opposita Vahl. (Labiatae), and the rootbark of Lantana camara L. (Verbenaceae). PMID- 2236290 TI - Antimalarial compounds containing an alpha,beta-unsaturated carbonyl moiety from Tanzanian medicinal plants. AB - Pure compounds were isolated from plant extracts with antimalarial activity. The extracts were obtained from the tubers of Cyperus rotundus L. (Cyperaceae), the rootbark of Zanthoxylum gilletii (De Wild) Waterm. (Rutaceae), and the rootbark of Margaritaria discoidea (Baill.) Webster (Euphorbiaceae). The most active compounds included (IC50 within brackets): alpha-cyperone (1) (5.5 micrograms/ml), N-isobutyldeca-2,4-dienamide (2) (5.4 micrograms/ml), and securinine (3) (5.4 micrograms/ml). A mixture of autoxidation products of beta selinene was found to be the most active antimalarial substances obtained from C. rotundus (5.6 micrograms/ml. PMID- 2236291 TI - Molluscicidal and antischistosomal activities of Zingiber officinale. AB - Experiments were conducted to study the major constituents of Zingiber officinale responsible for its molluscicidal activity and the effect of the active component on different stages of Schistosoma mansoni. Gingerol and shogaol exhibited potent molluscicidal activity on Biomphalaria glabrata. Gingerol (5.0 ppm) completely abolished the infectivity of Schistosoma mansoni miracidia and cercariae in B. glabrata and mice, respectively, indicating that the molluscicide is capable of interrupting schistosome transmission at a concentration lower than its molluscicidal concentrations. PMID- 2236292 TI - Cytotoxic and antitumor constituents in pericarps of Mallotus japonicus. AB - A variety of phloroglucinol derivatives isolated from the pericarps of Mallotus japonicus were assessed for growth inhibiting activity against human larynx (HEp 2) and lung (PC-13) carcinoma cells as well as mouse B16 melanoma, leukemia P388, and L5178Y cells. Most of these derivatives were proved to be significantly cytotoxic in culture. One of them, 3-(3,3-dimethylallyl)-5-(3-acetyl-2,4 dihydroxy-5-methyl-6-methoxybenzyl )- phloracetophenone showed an excellent cytotoxicity against all target tumor cells and a marked prolongation of life span in mice bearing L5178Y leukemia. PMID- 2236293 TI - Spectral assignment and cytotoxicity of 22-hydroxytingenone from Glyptopetalum sclerocarpum. AB - 22-Hydroxytingenone was reisolated from a new source, Glyptopetalum sclerocarpum M. Laws and, for the first time, its unambiguous 13C-NMR assignments were accomplished through the use of APT, HETCOR, and selective INEPT spectroscopy. Intense, but nonspecific cytotoxic activity was observed when this substance was evaluated with a battery of cell lines comprised of the P-388 lymphocytic leukemia, KB carcinoma of the nasopharynx, and a number of human cancer cell types, i.e. HT-1080 fibrosarcoma, LU-1 lung cancer, COL-2 colon cancer, MEL-2 melanoma, and BC-1 breast cancer. PMID- 2236294 TI - The cytotoxic principles of Pseudolarix kaempferi: pseudolaric acid-A and -B and related derivatives. AB - Pseudolaric acid-A and -B, the novel diterpene acids isolated from Pseudolarix kaempferi, and their related derivatives have been tested for cytotoxicity against KB, A-549, HCT-8, P-388, and L-1210 tumor cells. The results showed that pseudolaric acid-A and -B demonstrated potent cytotoxicity. The selectivity of pseudolaric acid-A and -B which inhibit the growth of particular cell types within the disease-oriented human cancer cell line panels is discussed. PMID- 2236295 TI - Fractionation and characterization of mitogenic and anti-complementary active fractions from kampo (Japanese Herbal) medicine "juzen-taiho-to". AB - "Juzen-Taiho-To" (TJ-48), which is a kampo (Japanese herbal) medicine prepared by decocting a prescription of ten kinds of herbs, has several immunostimulating activities. In order to characterize the active substances for anti-complementary and mitogenic activities, TJ-48 was fractionated. Anti-complementary activity was observed in the water- and methanol-insoluble fraction (F-2) and the crude polysaccharide fraction (F-5), whereas mitogenic activity was only found in F-5. However, other low molecular mass fractions did not show both activities. Methylation analysis indicated that F-2 mainly contained amylopectin-like polysaccharides. Both Pronase digestion and periodate oxidation decreased the anti-complementary activity of F-2, and the beta-amylase-resistant fraction of F 2 still retained the potent anti-complementary activity. When F-5, which has the most potent of both activities, was further fractionated, only the major acidic polysaccharide fraction, F-5-2, showed potent mitogenic activity. Endo-alpha-(1-- -4)-polygalacturonase digestion showed that F-5-2 mainly contained pectic polysaccharides, and the endo-polygalacturonase treatment of F-5-2 reduced the mitogenic activity but not the anti-complementary activity. F-2 and F-5 each activated the complement system by a different mode of action. PMID- 2236296 TI - [Triterpenoid sapogenins in the genus Grindelia]. AB - A saponin fraction has been isolated from the ethanolic extract of Grindeliae herba. The saponin fraction showed strong haemolytic activity. The saponins were detected after separation on TLC by their color reactions and Rf values as well as by their haemolytic activity on blood agar. After hydrolysis, the chemical reactions and Rf values of the sapogenins were described. The main sapogenin was isolated by preparative chromatography and its structure was elucidated by mass, 1H-NMR, 13C-NMR, IR, and UV spectra. The compound is a new natural triterpenoid sapogenin lactone and is named grindeliasapogenin D. Spectral evidence is presented to establish its structure as 2 beta,3 beta,16 alpha,23 tetrahydroxyoleanan-28,13 beta-olide. Two further sapogenins present in small amounts were identified chromatographically as oleanolic acid and bayogenin using authentic reference substances. The aerial parts of Grindelia robusta Nutt, and G. lanceolata Nutt. (Asteraceae) (as well as two commercial extracts) were also investigated with respect to their saponin fraction. The 3 sapogenins mentioned above were detected in all samples. The antibiotic potency of the crude drug is not associated with the saponin fraction but is at least partially due to the resin fraction. PMID- 2236298 TI - Reconstruction of the vulva with V-Y advanced myocutaneous gracilis flap. AB - Reconstruction of the vulva with V-Y advanced triangular myocutaneous gracilis flap(s) is reported. Seven patients were treated with this technique following radical vulvectomy with two minimal complications. The reliability of this known flap and the usefulness of the V-Y advancement are stressed and make it a simple and successful technique. PMID- 2236299 TI - Surgical malpractice in the Renaissance and today. PMID- 2236297 TI - Structures of compounds with antigonadotropic activity obtained by in vitro oxidation of caffeic acid. AB - Two new cyclolignan derivatives were isolated by HPLC from the mixture of substances obtained after oxidation of caffeic acid with KMnO4. Their structures were elucidated by spectroscopic methods as 2,3-dicarboxy-6,7-dihydroxy-1-(3', 4' dihydroxy)-phenyl-1, 2-dihydronaphthalene (1) and 3-carboxy-6,7-dihydroxy-1-(3', 4'-dihydroxy)-phenylnaphthalene (2). Compounds 1 and 2 exhibit antigonadotropic activity as do the extracts of crude drugs of Lycopus europaeus and Lithospermum officinale after oxidation by plant enzymes. PMID- 2236300 TI - Auriculomastoid tube pedicle for partial ear reconstruction. PMID- 2236301 TI - The medial plantar flap. PMID- 2236302 TI - Suitability of the rat femoral vessel as a microsurgical model. PMID- 2236303 TI - Defining the viability of avulsed skin flaps by the split-thickness skin excision (STSE) test. PMID- 2236304 TI - Prevention of arterial spasm with transcutaneous catheters. PMID- 2236305 TI - Nasotracheal intubation in the presence of facial fractures. PMID- 2236306 TI - The degloving technique in the correction of hypospadias. PMID- 2236307 TI - Feminizing genitoplasty and clitoroplasty. PMID- 2236308 TI - Long-term effects of tissue expansion on cranial and skeletal bone development in neonatal miniature swine: clinical findings and histomorphometric correlates. AB - Progressive tissue expansion induces significant gross, histologic, and bony changes in skulls and long bones of neonatal miniature swine. These bony changes consist of erosion underlying tissue expanders, with bony lipping and bone deposition at the periphery of the expander. Cranial suture lines underneath expanders appear effaced and convoluted. Serial CT scans reveal decreased bone thickness and volume (p less than 0.02) but identical bone density (p = 0.60) beneath expanders. Increased bone volume and thickness occur at the periphery of expanders (p less than 0.02). Bone density (CT number) is unaffected by tissue expansion in both cranial and long bones. These findings have histomorphometric correlates: Osteoclastic bone resorption occurs underneath expanders with periosteal reaction at the periphery of expanders. Cranial sutures are similarly affected, but no cranial synostosis results. No changes to the inner table of the skull or stigmata of increased intracranial pressure were observed either in CT scans or in behavioral changes in long-term animals. The pathophysiology of bony changes is a remodeling effect, not one of simple pressure deformation. Increased bone resorption and complete inhibition of bone formation occur until the pressure is removed. Cranial bone is significantly more affected than long bone. After removal of the expanders, reparative bone remodeling begins within 5 days and nearly complete healing of the cranial defects occurs within 2 months (p less than 0.02). No plagiocephaly results despite early coronal suture changes. On the basis of this study, we conclude that tissue expansion causes significant but reversible effects, readily monitored by high-resolution CT scans, on neonatal and infant cranial and long bones. PMID- 2236309 TI - Treatment of craniomaxillofacial fibrous dysplasia: how early and how extensive? AB - Twenty-eight craniomaxillofacial fibrous dysplasia patients were treated as early as the symptoms occurred. The principles of surgical treatment were based on the zones of involvement: total excision of dysplastic bone of fronto-orbital, zygoma, and upper maxillary origin (zone 1) and bone reconstruction primarily; conservative excision on hair-bearing skull (zone 2), central cranial base (zone 3), and tooth-bearing bones (zone 4); and optic canal decompression on patients with orbital dysplasia and decreasing visual acuity. Patients were followed for 1 to 11 years (average 5.3 years). No recurrence or invasion of the fibrous dysplasia into the grafted bone was seen. One patient had orthognathic maxillary osteotomy on the reconstructed maxilla 6 years after initial reconstruction. Five of 19 patients with alveolar dysplasia had a recurrence and were reshaped. One patient had mandibular sagittal osteotomies to set back the prognathic, fibrous dysplasic mandible after three attempts at conservative shaving. Another patient with mandibular fibrous dysplasia had recurrence with pain and a hemimandibulectomy with successful immediate free vascularized iliac bone graft reconstruction. PMID- 2236310 TI - Lamellar split osteotomy: a new craniofacial technique. AB - Craniofacial osteotomies have by convention been bilamellar translocations of the entire substance of the dysmorphic bone. This approach limits the surgeon by reducing the stable bone mass available for fixation, creating dependence on concave surfaces. Most important, it changes the bony topography that determines the preoperative plan. This paper presents a new craniofacial concept and technique used in 26 patients with various dysmorphic syndromes who were reconstructed by performing a lamellar split osteotomy. This technique maintains the internal lamella in its native position, thereby allowing it to act as a reference for the bony topography and providing a stable facial framework for rigid fixation. This interlamellar osteotomy has led to improved aesthetic results in the orthomorphic reconstructions of congenital and other deformities. It can be used in any aesthetic patient in whom contour changes or augmentation of form is desired. It is recommended as a preferred method for achieving quantitative contour improvement in patients over 3 years of age. PMID- 2236311 TI - Improved primary surgical and dental treatment of clefts. AB - The improved combination of surgical and dental teamwork in the primary treatment of clefts presented here is consistent with principles. In fact, this is a staged design for correction of classic clefts of the lip and palate that, based on biological principles, facilitates the continuance of the failed embryonic "migrations" toward a normal end point. Positioning of the alveolar segments, dissection of mucoperiosteum out of the cleft, and union of mucoperiosteum across the alveolar and anterior hard palate cleft make it possible to create a periosteal tunnel across the bony gap and set up a condition conducive to bone formation and eventual tooth eruption in the cleft area. Lip closure by adhesion reduces the tension of the primary lip closure and allows gentle molding until solidification of the arch occurs. Thus a complete cleft has been rendered an incomplete cleft. With a balanced, stabilized maxillary platform, the definitive lip and nose corrections can be carried to completion early (by 2 to 4 years of age). These planned actions bypass a persistent cleft, fistulas, raw areas, malposition of alveolar segments, and probably the necessity for later bone grafting. The only question not totally answered is the effect of this approach on final growth. Although most reports seem to indicate that growth has and will proceed within normal limits, another 10 years of careful follow-up is indicated and, in fact, is in progress. PMID- 2236312 TI - Experience with the functional cleft lip repair. AB - The first 12 functional cleft lip repairs performed on unselected consecutive patients immediately following the completion of training by the author are presented. Previous reports on this cleft lip repair have shown excellent results but have always been based on patients operated on by the originator of the procedure. This report gives credence to the ease with which a cleft lip repair that gives reproducible good results can be taught and learned even by plastic surgeons with limited experience. It reviews the technical steps of the procedure, which emphasizes wide undermining and release of the orbicularis oris muscle on the lateral side of the cleft to allow redraping and lengthening of the lip skin, step-by-step layered closure of the mucosa, muscle, and skin, and further vertical lengthening of the lip with a Z-plasty skin closure. Three elements that are difficult to achieve or restore with cleft lip revision are evaluated: (1) achievement of a good skin scar, (2) maintenance of the alar facial groove, and (3) achievement of adequate lip height without sacrificing horizontal lip length. Ten of the 12 patients had a satisfactory scar, 9 patients had a good alar-facial groove, and all patients had a normal-appearing horizontal lip length. Nine patients required secondary surgery; however, in six patients, this included correction of the nasal deformity that was not corrected at the time of cleft lip repair. PMID- 2236313 TI - Primary repair of the bilateral cleft lip nose: a 15-year review and a new treatment plan. AB - For 15 years a forked flap has been used for columella reconstruction in primary repair of the bilateral cleft lip nose. With the adolescent growth spurt, three unfavorable features have become apparent: (1) the columella may grow too long and the nostrils too large, (2) often the nasal tip remains broad, and (3) there is a drift of the columellar base and the lip-columellar angle is transgressed by scar. This procedure has therefore been discontinued. A new treatment plan is presented in which the columella is reconstructed from tissues in the splayed-out nasal tip. PMID- 2236314 TI - Nasal reconstruction with full-thickness cranial bone grafts and rigid internal skeleton fixation through a coronal incision. AB - The use of iliac and rib bone as onlay grafts to the nasal dorsum often fails because endochondral grafts resorb unpredictably. Membranous cranial bone grafts are less likely to resorb, especially when used with rigid internal fixation techniques. However, when split, they are often too thin and can be difficult to contour. Full-thickness cranial bone grafts were used to achieve nasal augmentation in 26 patients with end-stage nasal skeleton deficiency. All procedures were carried out using only a coronal incision. Grafts were harvested through a craniotomy, carved meticulously, and secured rigidly with miniplates or bicortical screws. Donor sites were reconstructed with split cranial grafts, leaving an intact cranial vault. No graft was lost to infection, and there was no significant donor-site morbidity. In carefully selected patients this method of full-thickness cranial bone graft reconstruction yields good results. PMID- 2236315 TI - Simultaneous reconstruction of cervical soft tissue and esophagus with a gastro omental free flap. AB - A microvascular transfer of gastric tube and omentum was used to simultaneously reconstruct cervical soft-tissue and esophageal defects in five patients. All patients had previous high-dose radiation and multiple flap reconstructions. The largest esophageal and soft-tissue defects were 10 cm and 160 cm2, respectively. All wounds healed primarily except for one orocutaneous fistula. There was one death from an intraoperative stroke. The gastro-omental flap is useful in cases where the reconstructive surgeon is faced with both esophageal and soft-tissue defects--particularly in heavily irradiated patients who have few reconstructive options. PMID- 2236316 TI - Sixty consecutive breast reconstructions with the inflatable expander: a critical appraisal. AB - Breast reconstruction using inflatable expanders has become an established and preferred technique. Although our knowledge of the biomechanical changes occurring in expanded skin has increased greatly, little information is available regarding average aesthetic results achieved with this technique. In order to eliminate the bias of best case selection reports, this study of 60 consecutive patients undergoing skin-expansion breast reconstruction was undertaken. Results of the study demonstrated a significant frequency and diversity of complications. In particular, immediate breast reconstruction with skin expanders was identified as a high-risk procedure because of its association with skin necrosis and delayed wound healing. Although two procedures--insertion and replacement--had been anticipated, patients from both the Boston and New York groups required approximately three operations to complete the expansion process. Average aesthetic results, often characterized by problems of symmetry, ptosis, and contour, need to be recognized and improved. PMID- 2236317 TI - The radial forearm flap for reconstruction of the upper extremity. AB - The radial forearm flap, owing to its good-caliber arteries of long length and equally well distributed venous system, has proved very reliable. It has not only earned its place and recognition in reconstructive hand surgery, but also has emerged as a workhorse for the microvascular surgeon. We have used 14 radial forearm flaps for upper extremity reconstruction, and we present herein our experience. The technique of extracorporeal tissue transfer, which has been published elsewhere, was used in two patients and is detailed. Four representative patients are presented. PMID- 2236318 TI - A prospective clinical evaluation of autogenous vein grafts used as a nerve conduit for distal sensory nerve defects of 3 cm or less. AB - The purpose of this study was to determine the efficacy of autogenous vein grafts as nerve grafts (AVNC) for bridging of small peripheral sensory nerve gaps as compared with direct repair and with conventional nerve grafting techniques (ANG). Patients with painful neuroma or segmental nerve injury of 3 cm were chosen as the test group. Those amenable to direct repair were classified as controls. Between 1982 to 1988, a total of 22 patients were enrolled in this study. A total of 34 nerves were repaired, 15 with a venous nerve conduit, 4 with a sural nerve graft, and 15 with direct repair. Significant symptom relief and satisfactory sensory function return were uniformly observed. The two-point discrimination measurements indicated superiority of direct repair and probably of conventional nerve grafting. However, the universally favorable patient acceptance and the return of measurable two-point discrimination indicates the effectiveness of autogenous vein grafts as nerve conduits when selectively applied to bridge a small nerve gap (less than or equal to 3 cm) on nonessential peripheral sensory nerves. PMID- 2236319 TI - Calcium carbonate gel therapy for hydrofluoric acid burns of the hand. AB - Hydrofluoric acid is used extensively as an industrial cleaning agent for metals and glass. Many workers are injured by cutaneous contact of the acid with exposed skin surfaces, particularly hands. Hydrofluoric acid burns are characterized by delayed onset of symptomatology with skin ulceration, and severe pain may be of extended duration. Treatment of hydrofluoric acid burns traditionally has consisted of local infiltration or intraarterial injections of calcium solutions. These injections are painful and frequently require retreatment. A new treatment utilizing a topical gel of calcium carbonate is described. Nine patients have been treated for hydrofluoric acid burns of the hand with calcium carbonate gel applied topically and covered with occlusive glove dressings. A gel slurry is compounded from calcium carbonate tablets and K-Y Jelly. Fingernails of the affected fingers are removed if a subungual burn is obvious. The gel is put into a surgeon's glove and placed over the burned hand. The patient replaces the glove and slurry every 4 hours for 24 hours. After the first day, the glove is discontinued unless there is resumption of painful symptoms. Full range of motion is encouraged during this interval. The calcium carbonate gel technique was successfully utilized in nine patients with no further need for injection therapy. In these patients, pain relief was obtained within 4 hours of treatment, with no further progression of skin ulceration. No reconstructive procedures were required in any patient, and only one patient did not return to full-duty work within 1 week. There were no long-term sequelae from burns treated with this topical therapy, except one patient, who presenting 24 hours after the burn, developed a digital tip neuroma that was excised. PMID- 2236320 TI - Direct monitoring of capillary perfusion following normovolemic hemodilution in an experimental skin-flap model. AB - The effects of normovolemic hemodilution on skin flap survival are studied in a recently developed skin-flap model (homozygous hairless mouse ear) in which nutritional capillary flow is monitored directly by means of intravital microscopy from the time of flap creation throughout the establishment of necrosis. Two diluting agents (dextran 60 and hydroxyethyl starch 200) are utilized. Our quantitative findings demonstrate that the amount of nonperfused tissue following flap creation in both the dextran (n = 23) and starch (n = 13) groups was significantly decreased as compared with controls (n = 19). Our qualitative observations suggest that improved hemorrheologic properties at the microcirculatory level are responsible for the observed decreased necrosis. Various mechanisms by which hemodilution may act to prevent necrosis are discussed. PMID- 2236321 TI - Achieving standardized photographs in aesthetic surgery. AB - The plastic surgeon who wishes to share clinical experience with colleagues is obligated to produce accurate data in the form of photographs. Moreover, accurate photographs are essential to enable an objective critical appraisal of one's own surgical skill and to display postoperative results to patients in an unbiased fashion. Change should not be a function of either the photograph or the photographer. The use of an acetate screen grid in conjunction with anatomic boundaries is described as a means to achieve accurate, reproducible standard photographs of the face and body in aesthetic surgical patients. PMID- 2236323 TI - Growing up. PMID- 2236322 TI - Consecutive patients. PMID- 2236324 TI - The use of conchal cartilage graft in involutional entropion. AB - A simple and stable technique for repairing involutional entropion is described. Through a transconjunctival incision between the lower border of tarsus and the lower lid retractor, the eyelid is divided between the tarsus and the orbicularis oculi muscle into external and internal layers. The internal layer is moved upward until the eyelashes turn outward, and then through-and-through sutures are placed to fix it in this corrected state. The resultant defect between the lower end of the tarsus and the retractor is filled with a conchal cartilage graft. The raw surface of the cartilage is epithelialized from the surrounding mucosa within 1 to 2 weeks without shrinkage. This technique is more stable than any other technique that we have performed. PMID- 2236325 TI - Reduplication of the mouth and mandible. PMID- 2236326 TI - Controlled tissue expansion of a groin flap for upper extremity reconstruction. AB - A large upper extremity defect in an 8-year-old girl was resurfaced with an expanded groin flap. Tissue expansion allowed complete coverage of the defect while minimizing the donor deformity. Pretransfer expansion of pedicled flaps offers an alternative to free-flap reconstruction of complex upper extremity defects. This is especially valuable in the pediatric patient, in whom donor-site morbidity can be significant. PMID- 2236327 TI - Repair of a huge defect of the gluteal region by rotation of a combined tensor fasciae latae-sartorius myocutaneous flap. AB - Although the tensor fasciae latae myocutaneous flap is convenient for covering some defects in the gluteal region, it is not suitable to repair a huge defect because of its limited area. Based on the close relationship of the sartorius and the tensor fasciae latae at their origins and blood supply, the authors designed a myocutaneous flap containing both the tensor fasciae latae and the sartorius muscles and their skin territories with an area exceeding 800 cm2. Two successfully repaired patients are reported. The flaps provide normal sensitivity. The vascular pedicle has a reliable anatomy, being easily dissected, and averages 4.6 to 5.8 cm in length. Both muscles are expendable. There is little functional difficulty for hip joint after the operation. PMID- 2236328 TI - Secondary correction of the unilateral cleft lip nose using a conchal composite graft. AB - The secondary deformity of the unilateral cleft lip nose has many components. One is the dorsal dislocation of the lateral crus of the alar cartilage. We used a conchal composite graft positioned between the piriform aperture and the lateral crus and the upper lateral cartilage to correct this dislocation in nine patients. We believe that this graft is effective because it elevates the lateral crus of the alar cartilage off the depressed piriform aperture. This technique is very simple to perform, and it is easy to achieve nasal symmetry. Our results have been quite satisfactory, with no recurrence of dorsal dislocation. The donor site was covered by a subcutaneous pedicled flap from the cephaloauricular sulcus, leaving an inconspicuous deformity. PMID- 2236329 TI - The use of liposuction to contour cherubism. AB - Yet another application of suction lipectomy equipment is presented to remove the pathologic tissue in cherubism. Owing to the variations of consistency of the material in this condition, this technique may not be successful in all patients, but it is certainly recommended when indicated. PMID- 2236330 TI - Surgical correction of the inverted nipple with a tendon graft: hammock procedure. AB - Our procedure, in which the inverted nipple was suspended using autogenous tendon grafts, was easy to perform, and it was not necessary to cut the lactiferous ducts. There was no deformity of the nipple or areola after this procedure, and the surgical scars were inconspicuous. Three patients who were followed up for over 1 year after surgery were presented in this paper. In eight patients (13 corrected inverted nipples), good results were obtained and there have been no complications to date. PMID- 2236331 TI - Pharmacotherapeutics for the primary care physician. PMID- 2236332 TI - Pharmacotherapy and the primary care physician. AB - Clinical pharmacy services and pharmacotherapy specialists did not begin in primary care settings. Rather, the initial interdisciplinary teams took root in large hospitals and tertiary medical center inpatient services during the middle 1960s. By the early 1970s, however, numerous papers appeared that described a unique and exciting practice model that incorporated primary care physicians and clinical pharmacists. The sole purpose of the interdisciplinary concept was to allow each member to contribute their own expertise to improve patient care. In my experience, primary care physicians have been eager to consult clinical pharmacists and other health professionals. I believe that the reason for this is a fundamental philosophy that distinguishes these physicians from other medical specialists. Ingrained in their philosophy are concepts such as continuity of care and care of the entire patient. The latter relates, not only to multiple organ systems, but also the spiritual and behavioral characteristics of the person. The primary care physician is also viewed as the coordinator for all health care services required by their patients. Most primary care physicians welcome others' expertise as long as they continue to be the health care coordinator for the patient. The health care structure of the United States continues to shift to ambulatory care. This will provide additional opportunities for the types of group models described in this article. After 20 years, the positive impact that physician and pharmacotherapist teams can have on drug therapy is being recognized on a broader scale. These models should continue to move from the academic laboratory to private group practice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236333 TI - Therapy for hypercholesterolemia. AB - For most patients, hypercholesterolemia can be effectively lowered with drug therapy but only after several issues have been considered. First, drug therapy should never be considered without adequate dietary intervention. Dietary therapy may be effective for many patients with mild to moderate elevations in cholesterol. None of the drugs used to treat lipid disorders are benign agents. There is still debate about the interpretations of recent studies, the ability to generalize from studies to the whole population, and the cost effectiveness of drug treatment. Within the framework of the AHA and NCEP guidelines, an individualized approach to therapy is prudent. This should be initiated with maximal patient education because drug therapy will be maintained for the long term or for life. The LDL and HDL levels, age, sex, other CHD risk factors, cost of treatment, patient awareness, and motivation must all be assessed when making treatment decisions. When drug therapy is considered for patients with isolated hypercholesterolemia, bile acid sequestrants are the drugs of choice. PMID- 2236334 TI - Antidiabetic agents. AB - Although either insulin or oral hypoglycemics may be used in conjunction with diet and exercise in the management of type II diabetes, drug therapy for type I diabetes involves only insulin. C-peptide levels can be tested to assess whether the patient has remaining pancreatic endocrine function. Patients being started on insulin for the first time should receive a single injection of an intermediate-acting insulin of "human" origin at a dose of approximately 0.5 U/kg. Thereafter, fasting, mid-morning, mid-afternoon, bedtime, and possibly early morning blood sugars should be examined periodically to determine if the insulin dose needs to be increased, decreased, split, or if the patient needs to be on a two-insulin regimen. Intensive insulin therapy has become commonplace to control plasma glucose levels in the majority of patients receiving insulin therapy. Proper patient education regarding the insulin regimen, injection techniques, blood glucose monitoring, as well as diet, exercise, and foot care are essential if the patient's diabetes is to be controlled adequately. Guidelines for "adequate" glycemic control are outlined in Table 6. Recent evidence suggests that tight control of plasma glucose levels may decrease the macrovascular complications of diabetes. Although there is also evidence to suggest that the onset of microvascular complications might be delayed with strict glycemic control, the data are conflicting. The benefits of strict control must be weighted against the problems of hypoglycemia experienced by many patients who attempt tight control of their blood glucose levels. Biguanide compounds are available in Europe, but the sulfonylureas comprise the only class of oral agents in the United States commercially available for the treatment of type II diabetes. The two generations of these drugs reflect their potency and possible side-effect profiles. Of the first-generation agents, tolbutamide and chlorpropamide are the most widely prescribed. Tolbutamide is the weakest of the sulfonylureas, possibly making it a good drug for initiating oral therapy in the elderly. Chlorpropamide is becoming a less popular agent because of its long duration of action and its increased incidence of side effects. Of the second generation agents, glyburide offers a better dosing schedule (once daily compared with twice daily for glipizide); however, glyburide may produce a greater incidence of hypoglycemia, particularly in the elderly or in patients with significant renal impairment. There are few good studies comparing these two drugs so that recommending one over the other is difficult. Drug interactions are numerous with the first-generation drugs, but less so with the newer second generation agents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2236335 TI - Antibiotic therapy for common infections. AB - Several important points regarding the treatment of urinary tract infections should be made. Single-dose and short-course antibiotic therapy is appropriate only for women with acute bacterial cystitis due to E. coli. Studies comparing single-dose to full-course therapy have not been sufficiently designed to draw valid statistical conclusions, and only TMP/SMX is recommended at this time. Recurrent UTI in women is almost always due to reinfection, which is best managed by prophylactic antibiotics. Acute bronchitis and acute exacerbations of chronic bronchitis are often due to viral infections, and therefore antibiotic therapy is not always needed. In acute exacerbations of chronic bronchitis, the clearest success rates for antibiotic therapy have been in patients, who have all three of the following symptoms: increased dyspnea, increased sputum production, and sputum purulence. Mupirocin is an important addition to the agents used to treat bacterial skin infections due to streptococcal and staphylococcal strains. In impetigo, mupirocin has been demonstrated to be as effective or superior to oral erythromycin. In prostatitis, data on the fluoroquinolones appears impressive, but further comparative trials are needed. They may become first-line, empiric therapy. The newer oral antibiotics are not recommended as initial, empiric therapy in the outpatient management of common infections, with the possible exception of the treatment of prostatitis. These newer agents may be more important in the treatment of recurrent or resistant infections. PMID- 2236336 TI - Treatment of opportunistic infections associated with acquired immune deficiency syndrome. PMID- 2236337 TI - Therapy of affective disorders. AB - The key to the proper treatment of affective disorder is a correct diagnosis of the subtype of depressive illness. Thus, primary treatment recommendations include the TCAs for a depressive episode; ECT for a depressive episode with psychotic features; and MAOIs for dysthymic disorder and atypical depressive episodes. Nonresponding patients are treated with either lithium augmentation of TCA therapy, an MAOI, or ECT. Second-generation antidepressants are not usually indicated as initial treatments. They are recommended in situations in which their adverse-effect profiles offer significant advantages over TCAs in an individual patient. Second-generation antidepressants have not been extensively studied in patients who do not respond to TCAs. Maintenance antidepressant may be necessary to prevent recurrent depressive episodes. Lithium remains the mainstay of acute treatment of mania and for prophylaxis of subsequent affective episodes. In lithium-refractory or lithium-intolerant patients, carbamazepine is recommended. Valproic acid and verapamil have been useful, primarily in patients who do not respond to lithium and carbamazepine. PMID- 2236338 TI - Current issues in NSAID therapy. AB - More than a dozen NSAIDs are commercially available in the United States. Diclofenac may not be as effective for dysmenorrhea. Although most are equally efficacious, indomethacin is the preferred agent for hemicrania continua and chronic paroxysmal hemicrania. Although all NSAIDs should theoretically be beneficial in gout, the greatest experience is with indomethacin. Sulindac may be the preferred agent for diabetic neuropathy. Fenoprofen appears to be the most offensive NSAID in terms of nephrotoxicity. NSAIDs may antagonize antihypertensive therapy, although this effect may not persist beyond 1 month. Generally, use of NSAIDs in pediatric patients is limited to naproxen and tolmetin. Concomitant therapy with methotrexate, lithium, and AZT should be approached with caution. NSAIDs have similar propensities to cause gastrointestinal side effects. Sucralfate has consistently proved beneficial as cytoprotective therapy for use with NSAIDs without impairing absorption of the NSAID, NSAIDs generally should be avoided prior to surgery, although sulindac or nonacetylated salicylates have a negligible effect on platelet function and may be used if continued NSAID therapy is required. Hepatotoxicity, although rare with NSAIDs, is most common with phenylbutazone and least common with the fenamates. PMID- 2236340 TI - Drug use in pregnancy and lactation. AB - When prescribing drugs for patients who are pregnant or lactating, a clinician needs to ask the following questions: (1) Is pharmacotherapy necessary? (2) What drug can be used that has the lowest potential toxicity according to current knowledge? (3) What pharmacokinetic parameters does the drug follow during pregnancy? (4) What are the major risks inherent to this particular drug treatment? (5) Do the benefits outweight the risks? and (6) How can the risks be minimized by adjusting the drug dosage and duration? It is important to inform the patient of the possible risks and have her participate in making treatment decisions. If possible, the fetus or neonate should be monitored for adverse reactions during the course of treatment, and if any serious problems occur, the medication can be discontinued. Although it is true that no drug is totally without risk when used during pregnancy or lactation, if proper precautions are taken, then treatment can be rendered with minimal risks to both mother and child. PMID- 2236339 TI - Oral contraceptives. AB - Management of oral contraception requires an understanding of the relationships between the method's effectiveness, noncontraceptive benefits, and hormonal adverse effects. The new multiphasic combinations or OCs containing 35 micrograms of ethinyl estradiol and 0.5-1.0 mg of norethindrone or equivalent result in a maximum combination of efficacy and safety for the patient with minimal annoying problems for the patient and the prescriber. Patient education regarding early warning symptoms of adverse effects, breakthrough bleeding, and lack of withdrawal bleeding adds an additional margin of safety and reduces patient questions and uncertainties. PMID- 2236341 TI - Estrogen therapy during menopause and the treatment of osteoporosis. AB - Estrogen remains the single most effective agent in the treatment of menopausal symptoms and prevention of bone loss. This article focuses on the use of estrogen therapy during menopause and the pharmacotherapy of osteoporosis. Risks and benefits of hormonal therapy and regimen selection for menopausal women are discussed. The second section of the article focuses on current treatment strategies for osteoporosis. PMID- 2236342 TI - Chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease is indeed a multifaceted illness. The obstructive picture is the result of multiple pathologic processes. The most common cause is cigarette smoking. The key to decreasing the incidence of this disease is education to prevent people from starting to smoke and to educate those who do smoke to stop. The therapeutic management involves numerous medications, oxygen, and physiotherapy. Unfortunately, the pharmacologic management remains largely empiric with sympathomimetics, anticholinergics, methylxanthines, and corticosteroids. These agents, especially methylxanthines and corticosteroids, are not without considerable toxicity. Therefore, embarking on a pharmacologic plan requires weighing the risk to benefit ratio carefully and having a comprehensive plan to assess subjectively and objectively the efficacy and toxicity of the chosen therapy. PMID- 2236343 TI - Pharmacotherapy of asthma and allergic rhinitis. AB - It has become easier to treat and control the symptoms of asthma, while the treatment of allergies remains directed toward the prevention and blockade of histamine-induced symptoms. This article details treatment options, including beta-2 selective sympathomimetic agonists, methods of delivery, theophylline, cromolyn, corticosteroids, antihistamines, decongestants, and intranasal steroids. PMID- 2236344 TI - [Clinical study of postoperative delirium in the elderly]. AB - It is said that the surgery is often followed by a delirious state (postoperative delirium) in the elderly, but there are few reports on detailed studies of this condition. To determine the frequency with which postoperative delirium occurs in the elderly, its main causes and clinical characteristics, etc., the author made a clinical study of 127 patients, aged 60 years and over, who were about to undergo operations. In this study, polygraphy was used in a postoperative electrophysiological study. Of the 127 patients, delirium was noted in 20 (15.7%), there being little difference according to age or sex in the rate of occurrence, but in patients with malignancy, the rate was appreciably higher. Delirium became apparent between one day and two days after the operation and lasted for up to 6 days. We classified the types of delirium into the following three on the basis of clinical symptoms: hallucination type (5 cases), confusion type (8 cases) and hallucination-confusion type (7 cases). The possible causes of postoperative delirium include the patient's condition as shown in the pre and postoperative polygrams, the invasive effects of anesthesia and surgery (surgical procedures, length of time under anesthetic, time required for the operation, amount of blood lost and amount of blood received by transfusion, etc., the serum albumin before surgery, WBC after surgery, %delta PaO2, and whether ICU was used or not, and so on. Quite often in patients with postoperative delirium, the pre and postoperative polygrams show slow abnormality in the EEGs before surgery, and the eye movements of R(++)/RS pattern in the EOGs before and after surgery. Slow abnormality in the EEGs was much more frequently seen in the confusion type and hallucination-confusion type patients than in the hallucination type. In view of these results, we feel that any consideration of the occurrence of delirium must include the following factors. In cases where the effects of surgical invasion and metabolic disorder are greater, quite often consciousness is clouded following surgery. If the eye movements of R(++)/RS pattern is shown in the EOGs before surgery, as the clouding of consciousness is alleviated after the operation, considerable activity takes place in some of the brain's functions (those related to anxiety and tension, etc.) and a state of dissociation occurs in brain functions which would normally undergo integrated changes. It was thought that this dissociated state is manifested as the delirium. PMID- 2236345 TI - [Clinical study on depressive state following stroke]. AB - A clinical study was made on depressive state following stroke using stroke patients in the chronic stage. There were 118 stroke patients in the present study and 25 patients (21.2%) satisfied the diagnostic criteria for major depressive syndrome of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised (DSM-III-R). As for dispositional, social, and somatic factors, a tendency was observed for depressive state to develop at a high frequency among patients with a past history of mental disorder prior to development of stroke, patients residing in suburban area, patients engaged in domestic and agricultural work, and patients with a frequent history of physical disorders. A tendency was observed for depressive state to develop at a high frequency among patients showing B type in YG test and patients presenting laterality in electroencephalography. Among the 49 right stroke patients, depressive state was observed in 10 cases (20.4%), while among the 43 left stroke patients, depressive state was seen in 10 cases (23.2%) with the incidence of depressive state showing no difference by hemisphere stroke. Study of the clinical characteristics of depressive state by hemisphere stroke with the use of symptom items of Zung scale and Hamilton scale showed that patients in depressive state with right hemisphere stroke had high values in symptom items considered close to the essence of endogenous depression such as depressed mood, suicide, diurnal variation, loss of weight, and paranoid symptoms, while patients in depressive state with left hemisphere stroke had high values in symptom items having a nuance of so-called neurotic depression such as psychic anxiety, hypochondriasis, and fatigue. Comparison with endogenous depression patients indicated that right stroke patients rather than left stroke patients showed a clinical picture suggestive of endogenous depression. Antidepressant was effective in 71.4% of the cases, but no difference in effectiveness could be observed by hemisphere stroke. In stroke patients in the chronic stage the incidence of clinical depressive state was higher than 20%, and involved in its onset were not only brain organ lesions but also dispositional, social, and somatic factors and integration dysfunction in the emotional activity of the left and right hemisphere functions. As for the clinical picture, a picture considered close to endogenous depression was observed in right stroke patients, while that considered close to so-called neurotic depression was seen in left stroke patients. The therapeutic effect of antidepressant was almost equivalent to that for endogenous depression. PMID- 2236346 TI - [Clinical and psychopathological study of delusional depression--relationship between the etiology and their personality]. PMID- 2236347 TI - [Outcome of schizophrenia--extended observation (more than 20 years) of 129 typical schizophrenic cases (II)]. PMID- 2236348 TI - [A case of presenile dementia with peculiar speech-- palilalia]. PMID- 2236349 TI - [Eye movements in schizophrenia--relationships among eye movements under three experimental conditions; closed-eye, pursuit, and exploratory]. AB - In order to investigate the pathophysiology of schizophrenia using psychophysiological indicators of eye movements, this study was conducted to clarify relations among eye movements under three experimental conditions; closed eye, pursuit, and exploratory eye movements. Thirty-five chronic schizophrenic patients diagnosed by DSM-III-R criteria and 32 normal controls were examined. Horizontal eye movements were recorded electrooculographically with the subjects under two experimental conditions; one with eyes closed ("Closed-eye Eye Movement," Closed-eye EM), and the other with visually tracking a moving pendulum ("Pursuit Eye Movement," Pursuit EM). The closed-eye condition was further divided into two sub-conditions; one with the subjects awake and at rest, and the other with the subjects in the presence of a repetitive sound. Exploratory eye movements were recorded with an eye-mark recording system while the subjects viewing "S"-shaped geometric figures ("Exploratory Eye Movement," Exploratory EM). Indicators of eye movements under the three experimental conditions described above were measured and the correlations among them were investigated. Clinical symptoms in schizophrenics were assessed by BPRS, SANS and SADS and studied with the Factor Analysis method. In the Closed-eye EM, rapid eye movements appeared significantly more frequently and slow ones were less frequent in schizophrenics than in normals under both sub-conditions. The results for schizophrenics did not change significantly with the addition of sound stimuli. In the Pursuit EM, both the number and amplitude ratio of saccades were significantly larger in schizophrenics than in normals, although these indicators gradually decreased in both groups when tasks requiring concentration were demanded. In the Exploratory EM, the number of eye fixations, the total eye scanning length, and the "Responsive Search Score (RSS)," which is the total number of sections on which the eyes fixed during the response to the confirmative question, were all significantly smaller in schizophrenics than in normals. In schizophrenics, there were significant negative correlations between the RSS of the Exploratory EM and the number of rapid eye movements of the Closed eye EM, the RSS and the number, amplitude ratio of saccades of the Pursuit EM, respectively. On the contrary, in normals, significant positive correlations were found between the number of rapid eye movements and the number of saccades.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236350 TI - [Performance-psychologic cross-sectional study of young schizophrenic patients with a subchronic and chronic disease course]. AB - According to ICD-9 and DSM-III-R-criteria 14 subchronic schizophrenic male patients (duration of illness less than 2 years) and 17 chronically ill male schizophrenics (duration of illness between 5 to 12 years) matched for sex, age, education, type of illness, and medication were with the aid of 4 tests investigated with respect to time characteristics of performance parameters. Whereas subchronic patients revealed performance scores within the normal range of reference scores, chronically ill patients showed dissociative variations in performance (high scores in reasoning, low scores in speed factor). This can be interpreted as instability of brain functioning which characterizes schizophrenics suffering from a long duration of illness. Correlations between prolonged reactions to "crossmodal" choices and subjective basic symptoms in subchronic patients are hints at well established introspection ability of self regarded complaints. PMID- 2236351 TI - [Clinical and psychological test studies of the psychopathology of epilepsy]. AB - 46 patients with generalised epilepsy and 67 patients with partial epilepsy were examined in respect of basic psychopathological symptoms in the stricter sense: rate reduction, viscosity, and perseveration. Comparison of the groups of patients classified pathologically with 34 healthy control subjects enabled psychopathological calibration of the battery of tests involved. This is turn resulted in differentiated the presentation of the influence on the basic psychic symptoms of epilepsy as such and the nature and frequency of attacks. The concept of different pathogenesis for the phenomenologically different symptoms viscosity and perseveration is discussed. PMID- 2236352 TI - [Magnetoencephalography--current trends]. AB - The review deals with the method of magnet-encephalography. The physical principles and the most important technical conditions to put into practice this method are mentioned. Comparing with the electroencephalography this method shows various advantages, what leads to its intensive use for the localisation of components of evoked potentials, for the magnet-encephalographic record of the brain activity of the human fetus, and for the localisation of epileptic foci in therapy resistant epileptics. PMID- 2236353 TI - [Correlation of morphologic findings (CT) with clinical and relevant EEG findings in adult epileptics]. AB - In the Brandenburg Epileptics' Center, 165 adult patients underwent computer tomography diagnosis in addition to the usual neuropsychiatric and EEG findings checklist. The findings were incorporated into the diagnosis of epilepsy. Results are discussed and it is suggested that the inclusion of cranial computer tomography in the diagnosis and the findings checklist would be an optimisation. PMID- 2236354 TI - [Experiences with psychosocial management of patients with multiple sclerosis in a discussion group]. AB - Patients with multiple sclerosis must come to terms with their unpredictable chronic disease. Frequently, they want to establish contacts and exchange information with others sharing the same problems. Discussion groups of outpatients offer many opportunities to further the process of coping with the disease as an interlocking web of defensive and coping patterns. The patients can learn from each other to assess their disabilities and capabilities more realistically and to deal more openly with their fears, hopes and disappointments. PMID- 2236356 TI - The creative process: a functional model based on empirical studies from early childhood to middle age. PMID- 2236355 TI - [Acute tetraparesis in cervical spinal stenosis caused by chondrodystrophy]. PMID- 2236357 TI - Obsessive compulsive disorder and basal ganglia dysfunction. PMID- 2236358 TI - Prospective role for adenosine and adenosinergic systems in psychiatric disorders. PMID- 2236359 TI - Ernst Kretschmer 1888-1964. AB - Until his retirement in 1959 Ernst Kretschmer was Professor of Psychiatry at the University of Tubingen. He published eight monographs, five of which were of eminent importance and at least two exerted considerable influence on European psychiatry for several decades, namely Der sensitive Beziehungswahn (1918) and Korperbau und Charakter (1921). His theory on constitutional body types and character became an integral part of German schoolbooks. PMID- 2236360 TI - Neuropsychological deficits and CT scan changes in elderly depressives. AB - A number of computerized tests were used to study visual attention, memory and learning in elderly depressed patients. Impairment was found in approximately 70% of depressed patients and was seen particularly in memory and in measures of latency. Depressed patients showed equivalent impairment in short-term memory but less impairment in conditional associative learning compared to a group of patients with early dementia of the Alzheimer-type (DAT), matched for age and pre morbid IQ. With respect to qualitative differences between depression and DAT, depressed patients showed a different pattern of errors and a consistently prolonged latency of response which was independent of delay in a delayed matching-to-sample test. On recovery from depression, although improvement was seen in most test scores, performance in measures of latency and in a number of tests of memory and learning failed to reach the level seen in a group of matched control subjects and approximately 35% of patients continued to show impairment. For the depressed patients, ventricular brain ratio (VBR) correlated with measures of slowing. In addition, in the 'recovered-depressives', VBR correlated with poor performance at high levels of task difficulty. These findings are discussed with respect to previous literature on the pattern of cognitive impairment and CT scan findings in depression. PMID- 2236361 TI - Neuroradiological and neuropsychological assessment in anorexia nervosa. AB - Seventeen patients with anorexia nervosa were examined by computed tomography (CT) and psychometry and compared with ten normal control subjects. The patients were found to have enlarged external cerebrospinal fluid spaces compared to controls. No differences were found in ventricular size and X-ray absorption density measurements between patients and controls. The patients performed abnormally on the symbol digit test, the scores of which displayed a significant negative correlation with the CT scan changes. PMID- 2236362 TI - Psychiatric consequences of temporal lobectomy for intractable seizures: a 20-30 year follow-up of 14 cases. AB - Between 1958 and 1968, 14 patients from the epilepsy clinic at the University of Oregon Hospitals and Clinics with a diagnosis of temporal lobe epilepsy (TLE) had a temporal lobectomy for medically intractable seizures. Nine of the 14 patients operated on remained seizure-free over the 20-30-year period of follow-up. Between 6 months and one year following temporal lobectomy, two women, previously healthy from a psychiatric standpoint, developed psychoses, and the previous psychiatric problems of four other patients worsened. Two patients, one with incapacitating paranoid personality disorder and the other with explosive rage attacks preoperatively, had marked improvement in their psychiatric status following temporal lobectomy. The remaining six patients, all psychiatrically healthy prior to surgery, have had no change in psychiatric status following surgery. Development of psychosis or deterioration in psychiatric status after surgery was more common in patients with later age of onset, unreality or deja vu rather than epigastric aura, pre-operative evidence of bilateral brain damage, and persistence of EEG or clinical seizure activity. Development of a chronic psychosis in psychiatrically healthy individuals many months after temporal lobectomy, even when seizures are arrested or ameliorated, suggests that anomalous synaptic regeneration may follow the surgery in these cases. Careful analysis of histories and outcomes may contribute to better understanding of the pathophysiology and anatomical substrates of psychoses. PMID- 2236363 TI - Psychiatric aspects of HIV-1 infection and AIDS. AB - The literature on the psychiatric aspects of HIV-1 infection is reviewed. The whole range of psychiatric disorders described in HIV-1 infected subjects, from HIV-1 dementia to adjustment disorders, is covered, along with the AIDS-related psychopathology which may develop in subjects without HIV-1 infection. PMID- 2236364 TI - Psychological and physical determinants of premenstrual symptoms before and after hysterectomy. AB - The aim was to study women before and after hysterectomy (with conservation of the ovaries), in order to discover how far premenstrual symptoms are caused physically and how far psychologically. In such women both physical and psychological factors can influence premenstrual symptoms before hysterectomy; after the operation, in the absence of menstruation, only physical factors can do so. The subjects were 56 women awaiting hysterectomy for menorrhagia of benign origin. During three pre-operative months these women made daily self-ratings on a check-list in which typical premenstrual symptoms were interspersed with atypical symptoms; in this way their awareness of the premenstrual focus was minimized. Starting six months after hysterectomy, the women again kept daily check-lists for three months; over the same period their serum progesterone levels were measured to identify the premenstruum. After hysterectomy, levels of premenstrual symptoms fell significantly in the whole group, indicating that psychological factors were important determinants of such symptoms before hysterectomy. PMID- 2236365 TI - Sampling strategy in linkage studies of affective disorders. AB - Evidence of linkage in families of bipolar patients has so far been identified with genetic markers on chromosome X and 11. However, replications of these data have not consistently been reported in either case, which favours the hypothesis of genetic heterogeneity. Therefore, we have tried to outline a sampling strategy for linkage replication in affective disorders. We estimated the average number of nuclear families required to replicate X or 11 linkage as a function of the degree of heterogeneity as well as the number to prove heterogeneity given that linkage exists. The results are presented and discussed. PMID- 2236366 TI - Genetic and environmental determinants of the lability of trait neuroticism and the symptoms of anxiety and depression. AB - A genetic analysis was conducted on trait neuroticism and symptoms of anxiety and depression in a five-wave study of 462 twin pairs. Models that assessed the relative importance of genetic and environmental factors to the lability (within individual variability over time) of these measures were fitted to the data. Previous results concerning the substantial genetic involvement in the level of neuroticism and symptoms were confirmed. However, it was found that neither genes nor the shared environment of the twins was a significant cause of lability of these measures. An attempt was therefore made to identify aspects of individuals' environments that might be responsible for lability of neuroticism and symptoms. Adverse life events were found to predict variability of symptoms, but not of neuroticism. The availability of close social ties or having affectionless control in childhood did not contribute to lability. PMID- 2236367 TI - A contribution of fluorescent lighting to agoraphobia. AB - Under three types of artificial lighting 24 women with chronic agoraphobia and 24 female control subjects assessed their mood and bodily symptoms, and their heart rate was measured. One of the three types of lighting was incandescent. The other two were fluorescent, one pulsating in the conventional manner 100 times per second and the other relatively steady. Both were provided by a single fluorescent lamp controlled from one of two circuits. When exposed to the conventional pulsating fluorescent light under double-blind conditions the agoraphobic group showed a higher heart rate and reported more anomalous visual effects in response to an epileptogenic pattern. Control subjects reported more bodily symptoms under the conventional fluorescent light than under the two other lighting conditions. PMID- 2236368 TI - Cognitive processing in post-trauma reactions: some preliminary findings. AB - The current study investigated a model of post-trauma reactions proposed initially by McFarlane (1988 a). Two separate data sets, one obtained following a multiple shooting and the other reported by McFarlane following a natural disaster, were examined. The findings of both studies provide support for a cognitive processing conceptualization of the development of post-trauma reactions. PMID- 2236369 TI - Psychological treatment for atypical non-cardiac chest pain: a controlled evaluation. AB - Thirty-one patients with atypical non-cardiac chest pain which had persisted despite negative medical investigation were treated in a controlled trial of cognitive-behavioural therapy. The average duration of pain was 4.7 years. Patients were randomized to either immediate treatment or as a control to assessment only. Treatment involved teaching patients how to anticipate and control symptoms, and modification of inappropriate health beliefs. The average number of sessions given was 7.2. There were significant reductions in chest pain. limitations and disruption of daily life, autonomic symptoms, distress and psychological morbidity in the treated group as compared with the control group who were unchanged. The assessment-only group were treated subsequently and showed comparable changes. Improvements were fully maintained by both treated groups at four- to six-months follow-up. PMID- 2236370 TI - Perceived parental rearing style, parental divorce and transsexualism: a controlled study. AB - The parental representations of male-to-female and female-to-male transsexuals were rated using the EMBU inventory. Scores on the measure were compared against ratings returned by controls of similar biological sex, matched on age, educational level and number of female siblings in an ANCOVA design. In line with previous findings by Parker & Barr (1982), who studied male-to-female transsexuals only, these patients were found not to differ from the male controls in their scoring of their mothers, but did score their fathers as less emotionally warm, more rejecting and more protective. Extending the findings by Parker & Barr (1982), female-to-male transsexuals rated both parents as more rejecting and less emotionally warm, but only their mothers as more protective than their female control equivalents rated theirs. Parental divorce distinguished both patient groups from controls, although further analyses revealed this not to imply more parental absence in patients than in controls. Male and female transsexuals differed from each other in some respects (e.g. lower scores on parental emotional warmth and higher scores on maternal rejection for the female patients), while being comparable in other respects (e.g. parental divorce). PMID- 2236371 TI - Obsessional states: anxiety disorders or schizotypes? An information processing and personality assessment. AB - This paper presents evidence that on an information processing task, designed to investigate putative inhibitory mechanisms in selective attention, obsessive compulsive disordered individuals can be clearly distinguished from other anxiety disorder clients and show significantly higher scores on questionnaire measures designed to detect schizotypy in the normal population. It is suggested that these results provide some support for the idea that obsessive-compulsive disorder may be misclassified as an anxiety disorder and may in fact be categorically more closely aligned to the schizophrenic constellation of disorders. PMID- 2236372 TI - Lycanthropy and demonomania: some psychopathological issues. AB - Modern reports on lycanthropy mainly concentrate on the content of patients' beliefs in being transformed into an animal. By contrast, an interest in the form of the symptomatology is usually minimal. This paper draws on Karl Jaspers' phenomenological views and focuses on some important albeit neglected psychopathological issues related to form which are relevant to any comprehensive consideration of lycanthropic phenomena. PMID- 2236373 TI - Hypertension labelling, life events and psychological well-being. AB - Almost all previous studies of the psychological sequelae of hypertension labelling have lacked a prospective, longitudinal design which could allow for causal interpretations. The present study relies on questionnaire data from a hypertension screening carried out on the entire adult population of a medium sized, Norwegian county (total number of participants = 74977). 'Labelled' individuals, i.e. previously unaware hypertensives (N = 173), false positives (N = 233), and patients in need of continued BP control (N = 474) have been followed up after 1-3 years, and comparisons are made with aware hypertensives (N = 206), patients previously treated for hypertension (N = 118), and a random sample of normotensives (N = 2326). 'Pre-labelling', baseline measures of subjective well being had been carried out on all comparison groups in connection with the screening. Changes in psychological well-being are not significantly related to labelling or BP-status. However, there is a deterioration in psychological well being among participants who have been subjected to one or more negative life events/stresses (other than labelling) in the preceding 12 months. PMID- 2236374 TI - Neurotic symptoms and subjective well-being in a community sample: different sides of the same coin? AB - Community survey data on neurotic symptoms and subjective well-being scales were examined with principal components analysis. The two types of scales were found to load on separate, but negatively correlated, factors. Furthermore, some differential correlates of the two types of scale were found, but the differences were not great. It was concluded that neurotic symptom and well-being scales do largely measure different ends of a single continuum, but well-being scales seem to have an extraversion component not shared by neurotic symptom scales. Subjective well-being measures may be useful in epidemiological surveys where it is desirable to discriminate among low symptom scorers. PMID- 2236375 TI - Life events and social stress in puerperal psychoses: absence of effect. AB - Thirty-three patients admitted to hospital with severe early onset puerperal psychiatric disorders were compared with matched normal puerperal controls. Interviews, which were administered after recovery, covered life events in the previous thirteen months and detailed assessment of previous and personal history, pregnancy and labour, other aspects of stress, social support, and marital relationships. No differences, except for previous history of psychiatric disorder, were found between patients and controls or between patients with depressive and with other diagnoses. These findings of absence of social stress contrast with previous studies of milder post-partum depression and of disorders with onset during pregnancy, and suggest that the aetiology of severe post-partum disorders is predominantly biological. PMID- 2236376 TI - Type A stress prone behaviour and breast cancer. AB - This quasi-prospective study of 2163 women attending breast-screening clinics (and controls), indicates that there is a link between personality factors and breast disease. Certain aspects of Type A behaviour seem to be associated with breast-disease states. PMID- 2236377 TI - Prevalence of three bulimia syndromes in the general population. AB - Prevalence of bulimia was estimated from a cross-sectional general population survey of 1498 adults, using the Diagnostic Interview Schedule (DIS) administered by trained lay interviewers. Lifetime prevalence of the DSM-III syndrome in adults aged 18-64 was 1.0% and this was concentrated in young women: in women aged 18-44 lifetime prevalence was 2.6%, and 1.0% currently had the disorder. Based on clinicians' reinterviews of random respondents and identified and marginal cases, the prevalence of current disorder using criteria for draft DSM III-R bulimia was 0.5%, for DSM-III it was 0.2%, and for Russell's Criteria bulimia nervosa 0.0%. A strong cohort effect was found, with higher lifetime prevalence among younger women, which is consistent with a growing incidence of the disorder among young women in recent years. Although elements of the syndromes were so common as to suggest that dysfunctional attitudes to eating and disturbed behaviour surrounding eating are widespread, there was little evidence of the bulimia syndrome having become an epidemic on the scale suggested by early reports. PMID- 2236378 TI - Mental health and medical consultation in primary care settings. AB - This paper examines the effect of psychiatric morbidity, as measured by the GHQ 60, on the probability of being in contact with a primary care physician, and the socio-demographic factors which influenced this effect. We found that the presence of psychiatric morbidity emerged as a major determinant of primary care utilization in both sexes, and about one-sixth of consultations in men and one fifth of consultations in women could be attributed to it. Logistic modelling was used to investigate the joint effect on general practitioner consultation of psychiatric morbidity and seven socio-demographic variables. Sex, age, and psychiatric morbidity exerted independent, but not interactive, effects on consultation. PMID- 2236379 TI - Estimating psychiatric morbidity by logistic regression: application to post natal depression in a community sample. AB - The use of logistic regression to estimate the prevalence of psychiatric morbidity in community samples is illustrated here with data from a study of post natal depression in 702 primiparous Cambridge mothers. The method is also used to validate the primary screening instrument (in this case the Edinburgh Postnatal Depression Scale--EPDS), and to estimate the effects of cofactors, such as maternal age, previous psychiatric history and social class. PMID- 2236380 TI - Quality of life in chronically mentally ill patients in day treatment. AB - A structured assessment instrument, the Quality of Life Interview, was used to explain the quality of life of seventy patients with chronic psychiatric illness attending a day treatment programme. The interview was found to have acceptable psychometric properties. Factors that best predicted the quality of life of these patients included the number of re-admissions in the last year, frequency of family contacts, satisfaction with social life, psychiatric health and adult education. The theoretical implications and potential clinical benefits of these findings for chronic psychiatric patients are discussed. PMID- 2236381 TI - Psychiatric morbidity among Punjabi medical patients in England measured by General Health Questionnaire. AB - The 28-item GHQ was administered to 282 Punjabi and white British patients visiting two Health Centres in Bedford. We discovered that ethnicity is not significantly correlated with GHQ 'caseness', but that differences exist in somatic and depressive symptomatology. The discussion relates these findings to debates about the psychiatric morbidity of Asian immigrants and somatization. PMID- 2236382 TI - Do mental health surveys disturb? AB - We have tested the assumption that mental health surveys do not cause distress. At the end of a two-wave community survey of psychiatric symptoms and personality factors, respondents were asked specific questions about how the interviews affected them. Being interviewed was distressing for some individuals, but it was seen as beneficial by a larger number. Those reporting distress were more likely to have had neurotic symptoms prior to both interviews and to have personality characteristics which would indicate proneness to distress. Whether the distress lasted beyond the interview situation is unknown. These results suggest that surveys of mental health should tell intended respondents about the possible effects of the interview, both positive and negative. Some studies should try to estimate the duration of any distress reported to have been induced. PMID- 2236383 TI - A model of stability and change in minor psychiatric symptoms: results from three longitudinal studies. AB - A statistical model designed to estimate the contributions of stable and changing symptomatology to levels of minor psychiatric symptoms is developed. This model is fitted to data obtained from three longitudinal studies. These studies involved subjects from Canberra (Australia), Christchurch (New Zealand) and Groningen (Holland). Data from all three data sets were shown to fit the proposed model adequately. However, there were systematic differences in the findings of the study. The findings from the Canberra and Groningen studies suggested that a large amount (50-75%) of the variance in symptom levels could be attributed to between subject difference in stable levels of symptomatology. In contrast the Christchurch study suggested a smaller contribution of stable symptomatology. These differences may be explained by the nature of the samples studied. All three studies showed evidence of strong correlations (0.79-0.94) between stable levels of symptomatology and the measure of trait neuroticism. It is concluded on the basis of this evidence that the neuroticism may be little more than a way of measuring the subject's characteristic level of minor psychiatric symptoms. The model also made it possible to secure estimates of the extent to which measures of neuroticism were contaminated by short-term mental state. Estimates of contamination effects varied between studies. For the Canberra data contamination was negligible, for the Groningen data mild contamination effects were present but for the Christchurch data contamination was larger. These differences may be explained by differences in the nature of the samples studied. PMID- 2236384 TI - Marital conflict and children's adjustment: a cognitive-contextual framework. AB - Marital problems have been related to numerous indexes of maladjustment in children. Although several parameters of this association have been identified, the process by which exposure to interparental conflict gives rise to adjustment problems in children is largely unexplored. Research on the link between marital conflict and child maladjustment therefore is critically evaluated, and a framework is presented that organizes existing studies and suggests directions for future research on processes that may account for the association. According to the framework, the impact of marital conflict is mediated by children's understanding of the conflict, which is shaped by contextual, cognitive, and developmental factors. The implications of the framework for children's adjustment are discussed. PMID- 2236385 TI - Enhancement of social learning family interventions for childhood conduct disorder. AB - Social learning family intervention (SLFI) is the treatment of choice for young children exhibiting severe conduct disorder and antisocial behavior. Despite the reported success of this intervention, high levels of resistance, poor engagement, and inadequate maintenance of improvements are observed for a substantial proportion of distressed families. These obstacles have inspired enhancement efforts to improve basic social learning family-intervention models. The present review identifies promising approaches for maximizing treatment gains for the conduct-disordered child. Relevant studies were organized into 3 approaches: enhancements and expansions (a) within a dyadic (parent-child) interaction model, (b) within a broad-based model that acknowledges a wider range of family influences, and (c) through a multisystems model. SLFI enhancements within the dyadic model have centered on either the strengthening of parental skills already included in the SLFI regimen or the adding of new interactional strategies. Some gains, but only partial success, have been achieved with the dyadic model supplements. SLFI expansions from a broad-based model have focused on parental adjustment, parental expectations during treatment, and social environmental stressors. The multisystems adjuncts to SLFI include cognitive behavioral interventions to affect peer relations and ecological approaches to sweep across domains. The broad-based and multisystems expansions have produced promising but undertested treatment regimens. Related areas of investigation included therapy process research, medication combined with SLFI, and the involvement of fathers in treatment. Recommendations are offered for improvement of SLFI research. The apparent theoretical crossroads for SLFI treatment of childhood conduct disorder are discussed. PMID- 2236386 TI - Burnout among Dutch psychotherapists. AB - The development of a Dutch adaptation of the Maslach Burnout Inventory is described. Preliminary results on burnout for 98 Dutch psychotherapists indicate that (on the average) young therapists and therapists who are employed in regional mental health services are more prone to burnout. PMID- 2236387 TI - Predicting alienation in a sample of Nigerian Igbo subjects. AB - Seeman in 1959 suggested that alienation is a multidimensional concept. Using two aspects of Seeman's concept of alienation, powerlessness and social alienation, and two concepts derived from Lachar's 1978 Minnesota Multiphasic Personality Inventory Cookbook, emotional and self-alienation, the present work was undertaken to ascertain which concept will more likely predict feelings of alienation. A stepwise multiple regression showed that among 160 Nigerian (Igbo) subjects the feeling of powerlessness predicted alienation more than did the other concept. PMID- 2236388 TI - What women think and what men think women think: perceptions of abuse and kindness in dating relationships. AB - The purpose of this study was to investigate how college women and their boyfriends viewed their relationships in terms of both abuse and kindness. The women filled out the Psychology Abuse-Kindness Relationship Inventory for themselves and their boyfriends responded to the questionnaire as they thought their girlfriends would. Several intriguing findings resulted: (1) Men thought their girlfriends would respond more negatively about the relationship than the women actually did. (2) Certain aspects of the relationship resulted in more discrepancies between the men's and women's perceptions. (3) Women distinguished present from past relationships by describing the former as more positive and the latter as more negative; men made no such distinction. Alternative explanations were offered to account for these results including projection, denial, projective identification, lack of psychological separation within couples, men's emotional upbringing and deeply rooted feelings towards women. PMID- 2236389 TI - Family satisfaction with medical care after traumatic brain injury. AB - Ratings during acute and follow-up care by 35 families having members with traumatic brain injury showed none of the medical facilities met families' needs though some aspects of patients' care were rated higher in hospitals. Findings suggest comprehensive surveys are needed. PMID- 2236390 TI - Beyond the psychiatric principle: a proposal for a psychological paradigm for the description and classification of psychopathology. AB - Dissatisfaction with the psychiatric system of classification of psychopathology has existed for decades. The many revisions have not rectified the many problems. An entirely different paradigm for the description and classification of psychopathology seemed necessary. Based on research, a proposal for a psychological system of classification of psychopathology is offered, one based on disorder in cognitive, emotional, and social functioning. A program of research to test the validity and heuristic value of this system is discussed. PMID- 2236391 TI - Individuation and adult children of alcoholics. AB - 42 adult male and 99 female volunteers from the Washington and Baltimore areas were administered the Psychological Separation Inventory, the Personal Authority in the Family System Questionnaire, the Adult Child of Alcoholics Screening Test, the Michigan Alcoholism Screening Test, and the Symptom-Checklist-90--R in a study of variables associated with the development of psychopathology of adult children of alcoholics. Individuation evolving from family dynamics rather than from intrapsychic individuation was more crucial to the development of psychopathology. PMID- 2236392 TI - Sibling variable correlates of children's academic achievement: family-group differences. AB - The study examined the proposition that relationships among sibling variables, intellectual ability, and academic achievement vary for children from different family-environment groups. Data were collected from 900 11-yr.-old Australian children and their parents. In the analysis, the children were classified into four family contexts that were defined conjointly by family social status and parents' academic socialization. Within each family group, regression surfaces were constructed from models that included terms to account for possible linear, interaction, and curvilinear associations among the variables. The results suggested the general proposition that within the family-environment groups, sibling variables were not related to academic achievement at different levels of children's ability. However, the findings indicated that there were variations to this general proposition. Indeed, there were a number of complex associations between the sibling variables and children's academic achievement in the different family-environment groups. PMID- 2236393 TI - Quantitative studies of responses elicited by selected TAT cards. AB - Quantitative differences in subjects' responses to selected TAT cards were studied. 70 white, female college students wrote stories in response to TAT Cards 1, 2, 3BM, 12M, and 13MF. Stories were scored for several measures of drive intensity, defensive pattern, and object relational pattern. On all measures, the several cards were associated with different patterns of response. The use of the pattern of scores on several cards (as opposed to aggregate measures summing responses to several cards) for exploration of the ebb and flow of various aspects of intrapsychic functioning is discussed. PMID- 2236394 TI - The Ways of Coping instrument: reliability and temporal stability for a sample of employees. AB - Convergent support is demonstrated for the use of seven empirically derived scales of the Ways of Coping instrument developed by Lazarus and his colleagues. While the instrument is widely used, until now the internal consistency of the coping measures and stability of the factor structure have yet to be shown for a sample of employed adults. While type of job and type of coping incident reported are not dependent, analysis indicates that work and nonwork groups differ across several coping dimensions. Research implications and directions are addressed. PMID- 2236395 TI - Solution acceptance by common ravens (Corvus corax) given two-bottle preference tests. AB - Two-bottle tests of solution acceptance were conducted in an outdoor aviary with eight common ravens (Corvus corax). Aqueous concentrations of the following chemicals were used: five common sugars, three salts, two acids, quinine hydrochloride, and sodium saccharin. Solution acceptance, as recorded for the different ravens on each test, was the percentage of preference shown for a test solution over water (comparison solution). Mid-range saccharin concentrations (0.10% to 0.80% [w/w]) were preferred over water in the tests. The preference for saccharin contrasts with all other reports on avian response to the chemical in two-bottle tests. Nonetheless, the ravens nonpreferentially accepted lower concentrations or were averse at higher concentrations to drinking sugar solutions. Similar, though more sharply marked, shifts from indifference to aversion were noted in tests with the other chemicals. The possible relevance of these latter findings to the food habits of ravens is discussed. PMID- 2236396 TI - Night waking and temperament in early childhood. PMID- 2236397 TI - Association of country, sex, social class, and life cycle to locus of control in western European countries. AB - Relatively few studies have focused on causal factors in the development of locus of control. Here nine western European countries are studied to assess the hypothesis that the society in which one lives is important in the scores on locus of control. The data indicate greater variation resulting from country of residence on locus of control than that from the variables of life cycle, sex, and social class. Findings regarding these latter variables are congruent with previous research. In addition, being single was related to having an external locus of control. PMID- 2236399 TI - Recollecting events associated with victimization. AB - Subjects first completed social desirability and anxiety personality scales and then read a story about a woman meeting her brother for lunch. Some subjects were then told that the story involved sexual abuse. A week later all subjects took a multiple-choice memory test over the story. The results indicated that subjects categorized as repressors based on the personality scales had a lower proportion of negative than positive errors than did the nonrepressors, but only when they believed the story was about sexual abuse. However, repressors answered correctly as many items as did nonrepressors. The results were consistent with the idea that repressors remember as much about victimization experiences as do nonrepressors but are more likely to fill in the missing details of victimization experiences with positive reconstructions designed to reduce the over-all negative quality associated with victimization. PMID- 2236400 TI - Suicide and presidential elections in the USA. PMID- 2236398 TI - Felonious murder of police officers by ambush. PMID- 2236401 TI - Prevalence of smokeless tobacco consumption at a southwestern university. AB - 265 students attending a southwestern university were surveyed about their use of smokeless tobacco products. 27% of 84 male respondents indicated they consumed smokeless tobacco. The women did not report routine use of smokeless tobacco. PMID- 2236402 TI - Low scores on California Psychological Inventory as predictors of psychopathology in alcoholic patients. AB - This study concerned the use of generally low California Psychological Inventory (CPI) profiles to predict elevated MMPI scores. In a sample of 110 subjects, a CPI profile with T-scores of 25 or less reflects major psychopathology and there is a 79% chance of correct prediction of MMPI T-scores over 80. As a further validation, a Goldberg Individual Index was established with a cut-off score of 70 to classify profiles as psychotic or nonpsychotic. It appears that the California Psychological Inventory can be expanded in making dual diagnoses for alcoholic patients. Scores can be used in treatment planning for alcoholic patients and to identify those individuals who should complete an MMPI for additional treatment planning and diagnoses. PMID- 2236403 TI - Adolescents' locus of control and compliance with contingency contracting and counseling interventions. AB - This study compared secondary school students' compliance with counseling or contingency contracting for truancy and disruptive behavior. Contracting was more effective than counseling with the 44 truants but not for those showing disruptive behavior (n = 52). Individuals with an internal locus of control were more responsive to counseling than those with external locus of control. PMID- 2236404 TI - Parental child-rearing attitudes associated with Type A behaviors in children. AB - The relation of Type A behaviors to parental child-rearing attitudes was assessed for 177 mothers, 153 fathers, and their children in preschools. Type A behaviors of children were measured on the Japanese version of the Matthews Youth Test for Health (MYTH), and parental child-rearing attitudes were measured on the Parents' Attitudes Test (PAT). Children were classified as Type A and Type B on the basis of their MYTH scores, and parental child-rearing attitudes in the two types were compared in a combination of parental sex (mothers vs fathers) and child's sex (boys vs girls). Analysis showed that especially mothers and fathers of Type A boys had less concern for their children than their peers whose boys were classified as Type B. The notion that boys showing Type A behaviors might develop Type A behavior patterns by striving to obtain more expression of concern or affection from their parents was presented. PMID- 2236405 TI - Citation patterns of the two social psychologies. PMID- 2236406 TI - Anger reactions of Iranian adolescents. AB - The purposes of this study were to examine the anger reactions of Iranian adolescents directed against their peer groups, parents, and teachers, or school faculties, and also to compare the results with Gesell's data from 1956. A questionnaire was developed according to Gesell's study to investigate the kinds of anger reactions 454 high school students (258 girls and 196 boys) expressed against their peer groups, parents and teachers, or school faculties. Adolescents used more crying against their fathers than mothers, peers, and teachers and more verbal aggression against their peers than their parents and teachers. For kind of anger reaction against parents and teachers or school faculties chi squared was significant across sex of adolescents. Finally, the kinds of anger reactions against mothers and stronger peers were significantly related to mothers' education. PMID- 2236407 TI - Effects of a forced institutional relocation on the mortality and morbidity of nursing home residents. AB - Residents of a county nursing home underwent a forced, mass relocation. Gerontologists advised on preparation of staff and residents. No increase in residents' mortality or morbidity was found after the relocation. The highest death rate was in the anticipatory period, the year prior to the move. PMID- 2236408 TI - Low self-esteem in eating disordered patients in the absence of depression. AB - Both low self-esteem and depression are well recognised as occurring in patients with eating disorders. 43 patients with eating disorders were studied to assess whether this low self-esteem occurred as part of an affective disorder or was independent of this. The patients, 23 with anorexia nervosa and 20 with bulimia nervosa, were assessed for low self-esteem, using the Rosenberg Self-esteem Questionnaire, and for depression, using the Hospital Anxiety and Depression Scale. The patients had low self-esteem, despite only a minority (33%) being depressed. This study demonstrates that low self-esteem occurs in patients with eating disorders in the absence of depression. PMID- 2236409 TI - Development and preliminary validation of a questionnaire assessment of expressed emotion. AB - A questionnaire for management of expressed emotion was constructed. It consisted of two scales, criticism and emotional overinvolvement. The questionnaire and the Camberwell Family Interview were then administered to relatives of schizophrenics and preliminary assessments of scale reliabilities and concurrent validities were done. Both questionnaire scales were reliable. With respect to validity the criticism scale correctly classified 88% of the subjects relative to the criticism scale of the interview. The emotional overinvolvement scale was less satisfactory (67%) but still assisted in classification of over-all expressed emotion. Expressed emotion, classification by the questionnaire, correctly identified 84% of the subjects with respect to the interview. PMID- 2236410 TI - Sources of meaning through the lifespan. AB - 185 men and women representing five developmental ages ranging from younger to older adulthood (17 to 96 yr) completed several measures to assess the amount and origins of most meaningful events in a person's life. As assessed by a modification of the Purpose-in-Life Test, the amount of purpose did not vary per se with age or sex. Similarly, the sources of meaning did not alter across time or sex. Themes of involvement emerged as the salient sources of meaning and included love, work, births of children, independent pursuits, accidents, illnesses, deaths, separations, or divorces, and to a lesser extent major purchases. The common sources and their timing are discussed within the context of a lifespan developmental model. PMID- 2236411 TI - Rational suicide: a test of the prescriptions of Epicurus concerning suicide. AB - The purpose of this research was to test the hypothesis that the individual who believes death is the end and who expects to experience more displeasure than pleasure over the remainder of his life will choose suicide. College students (N = 272) completed questionnaires measuring their beliefs about after-life, expectations of pleasure and displeasure should certain negative events happen to them, and expectations of suicide should these negative events happen to them. Support was not found for the hypothesis. The students who believed that death was the end stated that they would choose to live even if negative events promised them a life of greater displeasure than pleasure. PMID- 2236412 TI - Relating computer-associated stress to computerphobia. AB - The associations of computer-related stress, somatic complaints, and computerphobia were studied by administering questionnaires covering demographic data, exposure to computer information, computer-related stress, as measured by the Computer Technology Hassles Scale, somatic complaint items of the Hopkins Symptom Checklist, and Rosen, Sears, and Weil's measures of computerphobia: Computer Anxiety Rating Scale, Attitudes Toward Computers Scale, and Computer Thoughts Scale to 109 students. Correlations indicated scores on the Computer Technology Hassles Scale were significantly correlated .35 with somatic complaints, .27 with years used a computer, and .28 with self-rated computer knowledge. The Computer Technology Hassles Scale was not significantly correlated (.18, -.08, and -.05) with the three measures of computerphobia. Computer-related stress appears to be distinct from computerphobia. PMID- 2236413 TI - Therapeutic techniques vs therapeutic relationships in child behavior therapy. AB - The parents of 56 children who had received behavior therapy rated a number of variables, including the degree to which they viewed the therapeutic relationship versus the specific techniques used in treatment as important, the extent to which the child improved in therapy, and the child's present functioning. Therapists also provided ratings of clinical improvement. Even though parents gave the highest ratings for the importance of the relationship in therapy, the correlation between technique and clinical outcome was statistically significant while the correlations between the relationship and outcome was not. These statistical associations also held when therapists rated improvement. Also, therapists saw greater improvement in children than did the parents. Over-all, the results support the view that the relationship and techniques are interwoven and are both perceived as important factors in treatment. PMID- 2236414 TI - Relating locus of control to Machiavellianism and managerial achievement. AB - Rotter's Locus of Control Scale, Christie and Geis' Mach IV Scale, and Fineman's Work Preference Questionnaire were administered to a sample of 60 retail specialty store managers. While there were no significant correlations between locus of control and managerial achievement, there were significant correlations between locus of control and Machiavellianism for the over-all sample and for men but not for women. In addition, men possessed higher mean internal-control orientation than women. PMID- 2236415 TI - Medical resources and suicide prevention. PMID- 2236417 TI - Relationship between anxiety and premenstrual syndrome. AB - The relationship between symptoms of the premenstrual syndrome and anxiety was assessed for 68 women. The syndrome as measured by a modified version of the Moos Menstrual Distress Questionnaire, was correlated significantly with trait anxiety, as measured by Spielberger's State-Trait Anxiety Inventory. Trait anxiety was correlated with all three subtypes from the questionnaire: behavioral, psychological, and physical, most strongly for the psychological subtype. These findings suggest a role for stress-management training in the treatment of the premenstrual syndrome. PMID- 2236416 TI - Boredom proneness in pathological gambling. AB - To test the hypothesis that pathological gamblers seek stimulation as a means of reducing aversive under-aroused states of boredom and/or depression, the Beck Depression Inventory, Zuckerman's Sensation Seeking Scale and a Boredom Proneness Scale were administered to 48 diagnosed pathological gamblers and a control group of 40 family physician patients. Analyses of variance showed pathological gamblers obtained significantly higher boredom proneness and depression scores than those of controls. That the Boredom Proneness Scale failed to correlate with the Zuckerman Boredom Susceptibility subscale suggested the two measure differing dimensions. Results indicated the possible existence of three subtypes of pathological gamblers, one group characterized by boredom, another by depression, and a third by a mixture of both depression and boredom. PMID- 2236418 TI - Loneliness among Japanese and American college students. AB - Both Japanese and American college students (ns = 100), away from home at their first year in college, showed high scores in the Differential Loneliness Scale, with Japanese students scoring higher on all subscales. PMID- 2236419 TI - Differential effects of pet presence and pet-bonding on young children. AB - Pets have been shown to influence human development, but whether the effect is due to the presence of a pet or to the person's relationship with a pet is uncertain. Mothers rated their young children's companion animal bond (relationship) and social competence on a parental questionnaire, and a researcher assessed the children's empathy, cooperation, and intelligence during home visits. Significant correlations were noted between the children's bonds with their companion animals and their scores on the social competency scales as well as their empathy scores. The lack of similar significant pet presence ("ownership") correlations supports the hypothesis that the children's relationships with their pets are more important than just the presence of one or more pets in their homes. PMID- 2236420 TI - Relationship between scores on developing cognitive abilities test and scores on medical college admissions test for nontraditional premedical students. AB - The relationship of students' performance on the Developing Cognitive Abilities Test (DCAT), a test of scholastic aptitude, and their subsequent performance on the Medical College Admission Test (MCAT) were examined for 122 nontraditional premedical students who participated in a medical educational preparatory program. A stepwise multiple regression analysis produced moderate, though significant multiple correlations among subscores on the two tests. While there were a few exceptions, for the most part all of the subscores on the Developing Cognitive Abilities Test made a significant contribution to the regression equation in the prediction of scores on MCAT subtests. Implications for the value of the Developing Cognitive Abilities Test as an admissions tool as well as providing direction for possible intervention are discussed. PMID- 2236421 TI - Political behavior: voting participation of inner-city elderly blacks compared to other populations in a medium-sized city. AB - Voting participation was examined across nine elections in Omaha, Nebraska. Voting frequencies of all eligible voters in the city, all elderly eligible voters, and a random sample of inner-city elderly black voters were compared. The analysis shows that frequency of voting among inner-city elderly black individuals was the same as among all elderly persons in seven of the nine elections and significantly higher than that found among eligible voters of all ages in all nine of the elections. PMID- 2236422 TI - Educational needs of school personnel regarding child abuse and/or neglect. AB - From a review of literature a questionnaire was developed to identify problems related to child abuse/neglect in a rural school district. School administrators, regular and special education teachers, and counselors completed the survey to help establish more effective training programs. Analysis indicated that (1) school personnel need further assistance in dealing with problems pertaining to the maltreatment of students. (2) Formal, coordinated, workshop training for child abuse/neglect is needed. (3) Colleges and universities should offer instruction on abuse/neglect for persons preparing to work in schools. (4) School personnel need to be aware of and abide by the laws regarding reporting cases of abuse/neglect. (5) Improved communication among school, community, courts, and social service agencies is required for dealing wtih abuse cases. (6) School personnel should become more aware of what happens after abuse/neglect has been reported. Information from such analysis even for one school district can increase insight into problems. PMID- 2236423 TI - Attitudes toward autopsy refusal by young adults. AB - A survey of 158 18- to 24-yr. old college and 119 noncollege adults indicated that the latter were more reluctant to approve autopsies for spouses, children and distant relatives. Nonstudents also expressed more objections to autopsies than did students. PMID- 2236424 TI - Cognitive appraisal of daily hassles in college students showing Type A or Type B behavior patterns. AB - To test the hypothesized role of cognitive appraisal in Lazarus' model of life stress, 312 male and female undergraduate students completed the Hassles Scale and the Jenkins Activity Survey, Form C. Based upon their scores on the Type A scale of the Jenkins Activity Survey, subjects showing Type A behavior pattern differed significantly from subjects showing Type B behavior pattern on both reported frequencies of hassles (higher for Type A scoring subjects) and hassles content pattern. This is interpreted primarily as supportive of the cognitive appraisal variable in Lazarus' life stress model. PMID- 2236425 TI - Modification of the Word Association Test for assessing Posttraumatic Stress Disorders. AB - Suggestions for clinical modifications of the Word Association Test in assessing patients for Posttraumatic Stress Disorders are outlined. Two cases are briefly mentioned. PMID- 2236426 TI - MMPI comparisons of Hispanic- and white-American veterans seeking treatment for alcoholism. AB - Scores of 29 Hispanic- and 46 white-American alcoholics, who voluntarily sought psychiatric treatment for their alcoholism, were compared on the MMPI. It was hypothesized that Hispanic-American alcoholics would be better adjusted than white alcoholics on the validity and clinical scales of the MMPI. The hypothesis was supported, with Hispanic-Americans obtaining significantly lower scores than white veterans on the Pd, Mf, and Si scales. Hispanic and white patients did not differ on the remaining MMPI scales. The mean two-point code for Hispanic subjects was 2-8 (Depression-Schizophrenia) and for white patients 8-2 (Schizophrenia-Depression). PMID- 2236427 TI - Alcohol-related expectancies reported by college women to a large dose of alcohol. AB - A sample of 50 college women taking part in a previous study about expected effects of moderate doses of alcohol were contacted a second time. Of the original 50 subjects 47 now reported their expectancies for a large dose of alcohol both for themselves and for others by simply stating the three most probable effects in terms of behavior and emotion. They primarily expected themselves to become happy and others generally to misbehave. When answers were coded as positive or negative, subjects expected positive or negative effects both for themselves and others on the first choice. On the second and third choices, the proportion of negative expectancies increased significantly, especially for others. Results from the previous and the present study were compared, and it was concluded that subjects seem to have very few but dominant expectancies. PMID- 2236428 TI - Psychophysiology at the interface of clinical science, cognitive science, and neuroscience. AB - Research in schizophrenia illustrates that the field of psychophysiology lies at the interface of clinical science, cognitive science, and neuroscience. Electrodermal abnormalities in schizophrenic patients have been found reliably across laboratories, and data reported here demonstrate that these abnormalities are at least partially dependent upon the clinical state of the patients. Both tonic and phasic electrodermal activity increased when schizophrenic patients entered into a psychotic episode, and preliminary evidence suggests that the increases may serve as early prodromal signs of an impending episode. Significance of the electrodermal abnormalities for understanding cognitive and attentional deficits is suggested by associations with secondary reaction time and startle blink probe findings. Neuroscience implications are highlighted by the correlation of the electrodermal abnormalities with regional brain metabolic activity indexed by positron emission tomography. An important task for the future is to interrelate measures from these various domains. The field of psychophysiology is particularly well positioned for this task. PMID- 2236429 TI - Cognitive determinants of the postimperative negative variation. AB - This study examined cognitive determinants of the postimperative negative variation (PINV), a slow brain potential observable after the onset of an imperative stimulus in a forewarned reaction time task. Controllability of the aversive imperative stimulus by a motor reaction and predictability of the contingency were varied in a factorial design. The exogenous portion of the slow negative wave was assessed in a passive listening condition using tones of the same quality as the imperative stimuli, but presented without forewarning. Results show that PINV not only occurs when control is absent but also during unpredictably gained control. Similarly, unpredictable lack of control yields a more negative potential than continual helplessness. Negativity elicited by the aversive tone alone was not significantly different from PINV during predictable lack of control. The order of conditions, which was manipulated between groups, did not affect amplitudes. It was concluded that contingency change is a crucial cognitive determinant of the PINV, whereas the effect of lack of control is difficult to differentiate from the sensory influence of the acoustic stimulation. PMID- 2236430 TI - Aerobic fitness, physical activity, and psychophysiological reactions to mental tasks. AB - The association between aerobic fitness, exercise, and psychophysiological reactivity was assessed in cross-sectional and prospective analyses. Seventy-five healthy but sedentary adults carried out a sub-maximal exercise test and easy and difficult problem solving tasks. Blood pressure, heart rate, skin conductance level, respiration rate, tidal volume, and oxygen consumption were monitored and additional heart rate was also computed. Differences between relatively fit and unfit individuals were found in respiration rate during tasks and in skin conductance level during post-task recovery periods, with a tendency toward diminished heart rate reactivity in fitter people. Subjects were subsequently allocated to four conditions: high intensity aerobic training, moderate intensity aerobic training, an undemanding strength and flexibility program (designed as an attention-placebo condition), and waiting list control. Training programs were conducted over a 10-week period, and were followed by a second laboratory session. Appropriate changes in aerobic performance over the training period were observed in the 12-min run/walk test. There were no important modifications in psychophysiological stress reactions associated with the different experimental conditions. These results are discussed in relation to the literature concerning the effects of fitness and physical activity on physiological response patterns. PMID- 2236431 TI - Effects of stimulus repetition, duration, and rise time on startle blink and automatically elicited P300. AB - Intense auditory stimuli of sudden onset evoke not only startle blinks but also an event-related potential component resembling classic P300, even when subjects have no assigned task. To more closely examine the relationship of this P300 to startle, event-related potentials and eyeblink were recorded from 16 young adults in three paradigms designed to produce wide variation in startle amplitude: an Habituation series of 30-ms, 105dBA white noise bursts, a Duration paradigm which presented 105dB noise bursts for 3, 10, 30, or 90 ms, and a Rise Time paradigm which varied the rise/fall times (3, 15, 30, and 45 ms) of 110dBA, 1000-Hz tone bursts. Subjects received two runs of each paradigm. Only on the final Duration and Rise Time runs were stimuli explicitly task relevant; on those runs subjects rated verbally, midway in each 8.4-s interstimulus interval, the disturbingness of the prior sound. Although even the briefest noise bursts evoked parietal P300 as well as startle blink, P300 did not behave like startle. P300 habituated more slowly than did blink amplitude, was more responsive to sustained noise than were blink, N110, and P190, and most importantly, did not show the sensitivity to stimulus rise time manifested by these measures. These findings suggest that the amplitude of automatically elicited P300 is not governed by the same mechanisms as startle amplitude, but behaves more like a defense response. PMID- 2236432 TI - Maturation of startle facilitation by sustained prestimulation. AB - The startle response to a 104dB (SPL) 50-ms burst of white noise was facilitated by prestimulation with a nonstartling tone sustained for 2 s prior to the startling stimulus in 3, 4, 5, and 8 year old children and young adults. Both startle amplitude and onset latency showed significantly greater facilitation in the preschool children than in the 8-year-olds and adults. The results of this experiment, which used a fixed prestimulation interval, were compared to those of an earlier study in which the prestimulation interval was varied. The maturational changes in startle facilitation in response to the 2-s prestimulation interval were similar in the two experiments. Hence the maturational effect on startle facilitation was independent of the uncertainty (as to when the startling stimulus would be given), which might be associated with variable prestimulation intervals. These findings suggest that the neuronal mechanisms that mediate startle facilitation undergo development during early childhood and mature about 8 years of age, and that this maturational sequence is relatively independent of attentional effects. PMID- 2236433 TI - Do instructions modify effects of beta-adrenoceptor blockade on anxiety? AB - To study the interaction between physiological and cognitive factors in anxiety, 44 subjects with public speaking anxiety were allocated to four different groups. Two groups received either beta-adrenoceptor blockade (100 mg of atenolol) or placebo orthogonally crossed with an instruction that heart rate would decrease or an instruction that did not mention cardiovascular effects. During the delivery of a speech, measures of heart rate, systolic and diastolic blood pressures, and self-reported anxiety were obtained. All variables increased during an anticipation period before speech, and heart rate, systolic blood pressure, and self-reported anxiety increased further during speech. Regardless of instructions, atenolol decreased heart rate and systolic blood pressure during both anticipation and speech, whereas no differences were found in self-reported anxiety. This lack of a relationship was seen in spite of the correctly perceived heart rate reduction in the atenolol-treated group receiving an instruction that heart rate would decrease. Cardiac aware subjects, according to the Autonomic Perception Questionnaire, showed higher levels of heart rate and self-reported anxiety at rest than did cardiac unaware subjects. During speech, even though heart rate was similar in atenolol treated groups, self-reported anxiety was higher in cardiac aware than in cardiac unaware subjects. The lack of a relationship between heart rate and self-reported anxiety is discussed in terms of primary and secondary emotions. It is suggested that the perception of external rather than internal cues determines situationally elicited anxiety. PMID- 2236434 TI - Event-related potentials to visual and language stimuli in normal and dyslexic children. AB - Event-related potentials (ERPs) were recorded in 31 normal and 21 dyslexic children, the latter with visual processing impairment, in three visual reading related tasks: a nonalphabetic, an alphabetic, and a lexical decision task (two levels of difficulty in each). ERPs were recorded from fifteen active electrodes for 1.5 s following stimulus presentation; analyses were done on difference waves. N2 and P3 components were usually longer in latency and P3 was lower in amplitude in the dyslexic than in the normal children. The P3 had a flatter, broader distribution in the dyslexics than in the controls, which was very similar to the effect of difficulty in the two easier tasks. The lack of Group X Age interactions is inconsistent with either a maturational lag between the groups of children, or with the dyslexic children catching up to normals in terms of their speed of processing. Thus, the dyslexic children required more time to process the visual information across tasks (with only their letter classification being equal to that of the normal controls) and approved to have a different developmental pattern in their ERPs from that of the normal children. PMID- 2236435 TI - Effects of methylphenidate on processing negativities in patients with attention deficit hyperactivity disorder. AB - This study compared the impact of methylphenidate on patients with Attention deficit Hyperactivity Disorder (ADHD) with and without aggressive/noncompliant features in an oddball test consisting of a randomly ordered series of loud (frequent) tones, soft (rare) tones, bright (frequent) lights, and dim (rare) lights. In alternate conditions, subjects were required to respond to either the rare tones or the rare lights. These tasks were administered in a drug-free baseline session and after a counterbalanced treatment of 14 days each of methylphenidate (0.3 mg/Kg b.i.d.) and placebo (lactose b.i.d.). In comparison with placebo, methylphenidate resulted in greater accuracy and speed of reactions to targets of both modalities. The amplitude of N1 to auditory nontargets was larger when the target was a rare tone as opposed to a rare light, and this attention-related effect was increased by methylphenidate. The same differential amplitude enhancement by stimulant treatment was found for an early area measure of difference ERPs. In contrast, for N1 to visual nontargets the effect of selective attention (larger amplitude when the target was a rare light vs. a rare tone) was not significant and was not affected by stimulant medication. All these findings were comparable for the three ADHD subgroups, a result attesting to the generality of stimulant effects on information processing. PMID- 2236436 TI - Parietal P3 response as an indicator of stimulus categorization: increased P3 amplitude to categorically deviant target and nontarget stimuli. AB - Two experiments were performed in which we compared the effects of selected non deviant versus categorically deviant stimuli on parietal P3 under a variety of conditions in which one, both, or neither stimulus was a target of an experimental task. Subjects were repeatedly presented with series of 8 numeric stimuli and 1 alphabetic (Deviant) stimulus. P3 amplitudes to target and nontarget Deviant stimuli were consistently and significantly larger than to other, non-deviant targets and nontargets, respectively. Nontarget Deviant stimuli evoked P3 amplitudes comparable to those evoked by low-probability non deviant targets. The observed differences indicate that P3 amplitude is a sensitive indicator of perceived category differences, and that the effect of category deviance on parietal P3 amplitude is independent of task response classification (target or nontarget) and of response probability. PMID- 2236437 TI - What is "the vagal effect"? A rejoinder to Velden et al.'s interpretation of the cardiac cycle time effect. PMID- 2236438 TI - DMA-mode timing question for A/D converters. PMID- 2236439 TI - The power method for computing largest eigenvectors (principal components) of a dispersion matrix using minimal computer memory. PMID- 2236440 TI - Voluntary facial action generates emotion-specific autonomic nervous system activity. AB - Four experiments were conducted to determine whether voluntarily produced emotional facial configurations are associated with differentiated patterns of autonomic activity, and if so, how this might be mediated. Subjects received muscle-by-muscle instructions and coaching to produce facial configurations for anger, disgust, fear, happiness, sadness, and surprise while heart rate, skin conductance, finger temperature, and somatic activity were monitored. Results indicated that voluntary facial activity produced significant levels of subjective experience of the associated emotion, and that autonomic distinctions among emotions: (a) were found both between negative and positive emotions and among negative emotions, (b) were consistent between group and individual subjects' data, (c) were found in both male and female subjects, (d) were found in both specialized (actors, scientists) and nonspecialized populations, (e) were stronger when the voluntary facial configurations most closely resembled actual emotional expressions, and (f) were stronger when experience of the associated emotion was reported. The capacity of voluntary facial activity to generate emotion-specific autonomic activity: (a) did not require subjects to see facial expressions (either in a mirror or on an experimenter's face), and (b) could not be explained by differences in the difficulty of making the expressions or by differences in concomitant somatic activity. PMID- 2236442 TI - P300, probability, and interstimulus interval. AB - The relationship between target stimulus probability and interstimulus interval on the P300 (P3) component of the event-related potential was assessed in three experiments. In each study an auditory discrimination paradigm was employed wherein subjects indicated with a finger tap response the occurrence of a randomly presented 2000 Hz target tone embedded in a series of 1,000 Hz tones. Target stimuli were presented with a probability of either .20 or .80 in different conditions which were combined factorially with different interstimulus intervals. Experiment 1 presented stimuli at 2.0, 2.5, or 3.0 second intervals; Experiment 2 presented stimuli at 2.0, 3.0, or 4.0 second intervals; Experiment 3 presented stimuli at 4.0, 6.0, or 10.0 second intervals. P3 amplitude was larger for the .20 relative to the .80 target probability conditions for the shorter interstimulus intervals but not for the longer intervals. P3 latency was consistently longer for the .20 relative to the .80 target probability conditions, with generally little effect observed for interstimulus interval changes. The results suggest that interstimulus interval affects component amplitude by determining the amount of processing resources available when the P3 is produced. PMID- 2236441 TI - On the shift from anticipatory heart rate deceleration to acceleratory recovery: revisiting the role of response factors. AB - The influence of inducing motor responses of low and high force at different times in the cardiac cycle was examined. A handgrip response was used which allowed the separation of response initiation from response completion. Based on earlier work, we expected initiation, rather than completion, to initiate poststimulus cardiac acceleration. We also thought that preparation for a high force response might alter preparatory changes of interbeat interval differently from preparation for a low force response. Fifteen college-aged male subjects performed a warned reaction time task in which a visual stimulus signalled a handgrip requiring either a high or a low force to close. NoGo trials in which an inhibit signal was presented occurred on 12% of the trials. Stimuli occurred either on the R-wave of the electrocardiogram or 300 ms later. Reaction speed was varied in different trial blocks by rewarding response times of 200 ms (+/- 50 ms), 300 ms, or 400 ms. Results based on the timing of response initiation were essentially identical to those based on the timing of response completion. High force relative to low force was associated with both earlier response initiation and earlier cardiac acceleration. Force did not alter preparatory cardiac deceleration. Force and response speed did, however, alter the level of heart rate after response occurrence. Thus, response initiation (or an earlier response process) appears to induce a cardiac acceleration whose level is influenced by the speed and force of the motor response. PMID- 2236443 TI - Event-related potentials and recognition memory for pictures and words: the effects of intentional and incidental learning. AB - Event-related potentials were recorded under conditions of intentional or incidental learning of pictures and words, and during the subsequent recognition memory test for these stimuli. Intentionally learned pictures were remembered better than incidentally learned pictures and intentionally learned words, which, in turn, were remembered better than incidentally learned words. In comparison to pictures that were ignored, the pictures that were attended were characterized by greater positive amplitude frontally at 250 ms and centro-parietally at 350 ms and by greater negativity at 450 ms at parietal and occipital sites. There were no effects of attention on the waveforms elicited by words. These results support the view that processing becomes automatic for words, whereas the processing of pictures involves additional effort or allocation of attentional resources. The N450 amplitude was greater for words than for pictures during both acquisition (intentional items) and recognition phases (hit and correct rejection categories for intentional items, hit category for incidental items). Because pictures are better remembered than words, the greater late positive wave (600 ms) elicited by the pictures than the words during the acquisition phase is also consistent with the association between P300 and better memory that has been reported. PMID- 2236444 TI - Interpersonal influence as active coping: effects of task difficulty on cardiovascular reactivity. AB - This study examined the effects of attempting social influence on cardiovascular reactivity. Subjects were randomly assigned to a noncontingent reward condition or one of three conditions in which receipt of a monetary reward was contingent on their ability to influence another individual through a persuasive communication. In the contingent conditions, the task was presented as either easy, difficult, or very difficult. Measures of systolic blood pressure, diastolic blood pressure, and heart rate were recorded while subjects prepared and delivered the persuasive communication (contingent conditions) or reviewed and read aloud the same statement without an incentive to influence. The contingent conditions produced significantly higher levels of systolic and diastolic blood pressure and heart rate reactivity during preparation and speaking. Further, reactivity was higher in the difficult condition than in the easy and very difficult conditions. The findings are discussed in terms of an interpersonal equivalent of traditional active coping tasks. PMID- 2236445 TI - Topographic quantitative EEG in elderly subjects with major depression. AB - Some previous quantitative EEG research indicates that depressed subjects show increased alpha and beta compared to controls. In this report, absolute and relative amplitude measures of topographic EEG were used to compare elderly subjects with major depression to sex and age matched control subjects. Elderly depressed subjects showed significantly higher absolute alpha amplitude than controls, but regional differences did not specifically distinguish them. Relative alpha amplitudes, and absolute and relative measures of beta, delta, and theta did not reliably distinguish depressed and control subjects. The results are discussed in the context of previous EEG research in depression and the elderly. Methodological features and the implications of these findings for state and trait dependent conceptualizations of depression are considered. PMID- 2236446 TI - Menstrual cycle phase is a potential confound in psychophysiology research. AB - Effects of menstrual cycle phase on physiological levels and reactivity were studied in a within-subject design with 20 women aged 18-30 years. Basal body temperature was monitored daily; follicular and luteal recording sessions occurred before and after the ovulatory temperature rise, respectively. The design consisted of task and rest periods, presented in counterbalanced order across phases. Half the subjects began during their follicular phase and half began during their luteal phase. Follicular and luteal phases were compared for differences between baseline resting levels, as well as for reactivity. The results showed menstrual phase differences in heart rate, pulse transit time, and EEG alpha, particularly during tasks, but no difference in reactivity. Habituation effects in the group that began during the follicular phase often masked luteal activation. In spite of the fact that not all statistical results achieved significance, the consistency of most trends supports the conclusion that physiological recording sessions with women might best be restricted to the follicular phase. PMID- 2236447 TI - Detection of colon distension in colonostomy patients. AB - Inborn and learned ability to detect mild, nonpainful distension of the sygmoid colon was examined in 22 patients who underwent colonostomy one year or more before the investigation. The colon was distended by a balloon inserted 10 cm below the orifice of the artificial anus. Each subject participated in three sessions on three consecutive weeks with several experimental tasks in each session. During each task, the patient received the colon stimulus (the "signal") 25 times randomly paired with masking auditory or annular skin stimuli (around the stoma or 15 cm medially to it). The masking (warning) stimuli were administered in series of 50, representing the "noise," according to signal detection paradigms. The subjects had to indicate after each administration of the warning noise stimulus whether or not they thought the colon stimulus had been presented. In all three sessions, learning tasks were included using reinforcement of successful detection trials. Seven subjects out of 22 were considered good perceivers, 9 persons were considered medium perceivers, and the remaining 6 subjects were considered poor perceivers. According to the data of the first two groups, it can be hypothesized that most patients have some inherent sensitivity of colon distension, and that learning improves this initial ability. However, the role of skin, peritoneal, or interstitial receptors in colon distension detection cannot be excluded. PMID- 2236448 TI - Existing and training induced differences in aerobic fitness: their relationship to physiological response patterns during different types of stress. AB - Aerobic fitness has been associated with various desirable psychological and physiological characteristics. Recently, attenuation of physiological reactivity during stressful situations was added to this list, although comparison of the stress responses of sportsmen and sedentary subjects has yielded equivocal results. The present study examined cardiovascular patterns rather than single variables, and tried to clarify these matters. Tasks were used that were known to increase blood pressure through different combinations of changes in cardiac output and vascular resistance. Autonomic nervous system dynamics underlying these response patterns were studied using preejection period as an index of beta adrenergic activity, and respiratory sinus arrhythmia as an index of vagal activity. Pre-existing differences in aerobic fitness in a sample of sedentary subjects were related to their responses during the stressful tasks and the recovery periods afterwards. This approach prevented confounding of the relationship between fitness and stress-reactivity with the psychological effects of regular exercise. Furthermore, it excluded the bias in psychological makeup that is introduced when subjects spontaneously engaged in sports are compared to non-exercising persons. To rule out a third (hereditary?) factor underlying both stress-reactivity and fitness, physiological responses before and after a seven week training program were compared to those of subjects in a waiting list control group. Substantial individual differences in aerobic fitness were found in spite of the fact that all subjects reported low levels of habitual activity. During two active coping tasks, diastolic blood pressure reactivity and vagal withdrawal were negatively related to these pre-existing differences in fitness. No such relation was seen during a cold pressor test or during recovery from the tasks. Neither beta-adrenergic cardiac reactivity nor heart rate responses were related to fitness, but the absolute heart rate during the tasks was lower in the more fit subjects. Seven weeks of training were not effective in changing either reactivity or recovery of any of the variables. The discrepancy between cross sectional and longitudinal results in the present study suggests that training of longer duration is necessary to induce the psychological or physiological changes underlying reduced reactivity. The latter may include changes in cardiac vagal/sympathetic balance or in adrenoceptor sensitivity. Alternatively, both psychological and physiological determinants of stress-reactivity may be related to aerobic fitness at a dispositional level. PMID- 2236450 TI - The 29th annual meeting of the New Clinical Drug Evaluation Unit (NCDEU). May 30 June 3, 1989, Key Biscayne, Florida. Proceedings. PMID- 2236449 TI - Stimulus control and response measurement in human psychophysiological research using the Macintosh computer. PMID- 2236451 TI - Plasma GABA in mood disorders. AB - Plasma levels of gamma-aminobutyric acid (GABA) were determined in 68 healthy controls and in 133 patients with mood disorder. Plasma GABA levels were significantly lower in the patients with mood disorder compared to controls. Levels of plasma GABA were similar among diagnostic groups (primary unipolar depression, bipolar depression, mania, and secondary depression). No differences in plasma GABA were found in patients classified according to family history, nor were any correlations found between plasma GABA levels and severity of depression as determined by the 17-item Hamilton Rating Scale for Depression. These findings support the notion that low plasma GABA may represent a biological marker for mood disorder. PMID- 2236452 TI - Buspirone in depressed outpatients: a controlled study. AB - One hundred fifty-five outpatients suffering from major depression with significant anxiety entered a double-blind study comparing 8 weeks of treatment with buspirone or placebo. Twenty-nine percent of buspirone and 40 percent of placebo patients discontinued treatment before 8 weeks. Major efficacy measures were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D retardation and anxiety factors, the HAM-D Rickels and Bech core depression clusters, the Clinical Global Impressions (CGI), and the Hopkins Symptom Checklist (HSCL). Results were consistent across all outcome measures, including the two core depression clusters, with treatment response to buspirone significantly better than to placebo at treatment endpoint. Seventy percent of buspirone and 35 percent of placebo patients (p less than .01) were rated moderately or markedly improved after 8 weeks of therapy. Buspirone was found to be safe and well-tolerated by patients with major depression and concomitant anxiety at doses of up to 90 mg/day. PMID- 2236453 TI - Pattern analysis shows beneficial effect of fluoxetine treatment in mild depression. AB - In a multicentered study, 372 patients with mild major depressive disorder with a Hamilton Rating Scale for Depression (HAM-D) score of 15 to 19 were randomly assigned to 6 weeks of treatment with placebo or 20 mg, 40 mg, or 60 mg/day of fluoxetine. Patients were rated weekly for improvement and the appearance of side effects. Pattern analysis of treatment response showed more patients in the active drug treatment groups having a persistent or a delayed persistent response, the types of response specifically associated with active treatment. Analyses of mean changes in treatment measures showed little difference among treatment groups. This may be explained in part by different distributions in outcome, placebo patients having had a higher frequency of mild improvement with fewer negative and very positive outcomes. Response rate analyses favor the active treatments numerically, but only one of the comparisons is statistically significant. These findings suggest a specific role for fluoxetine treatment in mildly depressed patients who do not respond promptly or who respond inconsistently to nonspecific treatment. PMID- 2236454 TI - Avoiding neurotoxicity with lithium-carbamazepine combinations. AB - A therapeutic synergism has been well documented with carbamazepine (CBZ) and lithium in some patients who do not respond adequately to either drug alone. Because both of these drugs can induce neurotoxicity, concern has been expressed about their safety when combined. The serum levels for effective and safe dosage have been determined when these drugs are used alone. Unfortunately, this information does not give us automatic insight into the range of safe serum levels for each drug when these drugs are combined. We do not know whether the contribution of each drug to the neurotoxicity is the same. We have plotted the paired serum levels on a two-dimensional graph and quantitatively determined the region where we begin to encounter neurotoxicity. When we examine the available data on this graph, we see no evidence for synergistic neurotoxicity. PMID- 2236455 TI - Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. AB - Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects. PMID- 2236456 TI - Seasonal affective disorder: rapid resolution by low-dose alprazolam. AB - Seasonal affective disorder (SAD) has recently been recognized as a common psychiatric disorder, and treatment with bright artificial light has been shown to be effective in treating fall-winter SAD. However, many patients with SAD fail to respond or find phototherapy too inconvenient. We thus assessed the efficacy of alprazolam in 6 patients diagnosed with SAD during the course of ongoing clinical treatment. Alprazolam was administered in doses ranging from 0.5 mg to 1.5 mg daily. This agent produced rapid and dramatic results in 4 patients, with remission of symptoms occurring in about 3 days. These patients initially became hypomanic or hyperthymic, and then settled into a state of euthymia about 2 weeks later. Two patients had a moderate response but were still symptomatic. Five subjects received continuous treatment for at least an entire season, and none experienced withdrawal symptoms upon discontinuation. Alprazolam may represent an effective and well-tolerated alternative treatment for SAD. PMID- 2236457 TI - A single estimate of separate within-individual correlations: applications in psychopharmacology. AB - Simple procedures are proposed to describe relationships between sets of repeated measures within study subjects. An example is the association between blood levels of prolactin and a drug (e.g., methylphenidate) measured at multiple time points across study subjects. These procedures consist of (a) estimating Pearson product moment correlation coefficients (rs) within individuals using all the observations available per individual; (b) estimating an average r that pools the information across study subjects; (c) testing whether these rs are homogenous using a simple chi-square test; and (d) testing the average r for statistical significance. If these individual rs are found to be homogeneous, the average r is taken as representative of the individual rs. Testing rs for homogeneity and pooling them across individuals are relatively old procedures (Snedecor 1956). Recent applications can be found in the meta-analytic literature (Rosenthal 1983). Applications are demonstrated using actual data. We recommend using these procedures because they are simple and easily applied and interpreted. PMID- 2236458 TI - A clomipramine dosage reduction study in the course of long-term treatment of obsessive-compulsive disorder patients. AB - Ten patients with DSM-III-R obsessive-compulsive disorder (OCD) who were being treated chronically with clomipramine (270 +/- 20 mg/day) were studied to determine the minimum dose of clomipramine needed to maintain therapeutic benefit. These 10 patients were among the 17 of 18 patients recently reported to develop a return of OC symptoms following discontinuation of clomipramine under double-blind, placebo-controlled conditions. Each patient was rated twice--open and double-blind--at both initial and minimum doses of clomipramine, using the following three OC measures: the Yale-Brown Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health-Obsessive Compulsive Scale (NIMH-OC), and the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH Global OC Scale). Gradual, open dosage reduction resulted in a mean dosage of 165 +/- 19 mg/day, a reduction of 105 mg/day (approximately 40%, t = 5.55, p less than .001). This decrease in dose was accompanied by no significant change in the three OC measures, as determined by paired t-test. These results suggest that even though OCD patients were not able to discontinue medication completely, they were able to do well at lower doses than those used initially in treatment of the disorder. PMID- 2236459 TI - A placebo-controlled study of enciprazine in the treatment of generalized anxiety disorder: a preliminary report. AB - Enciprazine is a propanolamine derivative with a preclinical profile similar to buspirone but with less affinity for the postsynaptic dopamine receptor (Linden et al. 1988). We report on the outcome, using intent-to-treat data, of a 5-week, double-blind trial comparing three dose strengths of enciprazine (5 mg t.i.d., 10 mg t.i.d., and 20 mg t.i.d.) to placebo. A dose escalation was permitted after 2 weeks of active drug treatment, which 61 percent of patients overall took advantage of. A "last observation carried forward" (LOCF) analysis found a mean improvement in Hamilton Anxiety Scale (HAM-A) scores by Week 5 of -11.0 for the combined enciprazine treatment groups, and -4.4 for the placebo group (p less than .05). Fifty-two percent of enciprazine patients were judged to be "much" or "very much" improved, whereas none of the placebo patients were judged to have comparable improvement. Enciprazine was well-tolerated, with low levels of sedative and asthenic side effects reported. The compound appears to have promise as an anxiolytic agent. PMID- 2236460 TI - Behavioral response to methylphenidate and treatment outcome in first episode schizophrenia. AB - In order to examine the relationship of behavioral response to psychostimulants and acute treatment response, we administered methylphenidate (0.5 mg/kg i.v.), an indirect dopamine (DA) agonist, to 38 patients who met Research Diagnostic Criteria (RDC) for definite or probable schizophrenia or schizoaffective disorder, were experiencing their first acute episode of psychosis, and had received less than 12 weeks or no prior lifetime neuroleptic exposure. Following baseline methylphenidate infusions, patients received a standardized regimen of acute neuroleptic treatment. Methylphenidate produced an increase in psychopathology reflected by a worsening of both positive and negative symptoms. Using a priori criteria, 61 percent of patients exhibited psychotic symptom activation, and 39 percent showed no change. Activation during methylphenidate infusion during the initial acute phase of illness was not correlated with time to achieve antipsychotic treatment response but was associated with side-effect vulnerability. PMID- 2236461 TI - Steady-state pharmacokinetics of tacrine in patients with Alzheimer's disease. AB - Neurochemical studies of Alzheimer's disease (AD) suggest deficiencies in the cholinergic system. We evaluated the steady-state pharmacokinetics of tacrine (Cognex), an oral cholinesterase inhibitor, in 12 patients with AD. Patients sequentially received nine doses of 10 mg, 20 mg, and 30 mg of tacrine every 6 hours. Blood samples were collected until 24 hours after the final dose. Plasma tacrine concentrations were measured using a validated high-performance liquid chromatographic method. Mean maximum plasma concentrations (Cmax) were 5.1 ng/ml, 20.7 ng/ml, and 33.9 ng/ml following administration of 10 mg, 20 mg, and 30 mg doses, respectively. Corresponding mean values for steady-state area under the curve (AUC) were 19.7 ng/ml, 82.9 ng/ml, and 139 ng/ml.hr. Dose-normalized Cmax and AUC values after administration of the 20 mg and 30 mg doses of tacrine were comparable to each other but were significantly greater (p less than .05) than those after the 10 mg doses. The apparent elimination half-life was approximately 3.4 hours for all dosing regimens. Dose-dependent increases in Cmax and AUC values in patients with AD were similar to those previously reported in normal volunteers. The mechanism of the nonlinearity in tacrine pharmacokinetics is unknown. PMID- 2236462 TI - The effect of concomitant disorders in childhood depression on predicting treatment response. AB - Children with pure depression or depression plus an anxiety-related disorder (n = 14) had a higher drug response rate (57%) and a lower placebo response rate (20%) when compared to children with depression plus a concomitant conduct or oppositional disorder (n = 17) (33% drug response rate and 67% placebo response rate). These findings could explain why studies of prepubertal-onset depression found no differences between drug and placebo treatment assuming that a large percentage of the studies' subjects had concomitant conduct or oppositional disorders. The children with pure depression or depression plus an anxiety related disorder had different symptom clusters from those with depression plus a concomitant conduct or oppositional disorder. The former had more severe CDRS ratings on sleep, appetite disturbance, depressed feelings, and psychomotor retardation. In contrast, those with a concomitant conduct or oppositional disorder had shorter attention spans and were more likely to disturb other children (based on Conners scale scores). PMID- 2236463 TI - Saliva and serum lithium monitoring in hospitalized children. AB - Serum and saliva lithium levels are presented for 30 inpatients, ages 5.12 to 11.95 years, diagnosed as having conduct disorder of the undersocialized aggressive type. Maintenance doses of lithium carbonate ranged from 600 mg to 1,500 mg/day. Serum and saliva lithium levels were significantly correlated at optimal dose (r = .78, p less than .001) and overall (r = .83, p less than .001), lending support to the use of saliva lithium levels as an adjunct to serum lithium determinations. However, because saliva/serum lithium ratios reveal wide ranges between subjects, the use of saliva levels is limited, and laboratory assessments should be combined with careful clinical monitoring. PMID- 2236464 TI - Followup of adolescents initially treated for prepubertal-onset major depressive disorder with imipramine. AB - This preliminary followup of adolescents (n = 16) with prepubertal-onset major depressive disorder (MDD) suggests that a significant number continue to be depressed or possibly depressed (62%) and have moderate to severe ongoing psychosocial adjustment problems. A concomitant diagnosis of conduct or oppositional disorder at index assessment was a risk factor for an increased incidence of interim depressive episodes and more severe psychosocial adjustment problems including alcohol and drug abuse. PMID- 2236465 TI - S-adenosyl-L-methionine (SAM) in adults with ADHD, RS: preliminary results from an open trial. AB - The psychostimulants d-amphetamine and methylphenidate are thought to be the most effective treatment in children, adolescents, and adults with attention deficit hyperactivity disorder (ADHD) because they potentiate both dopamine (DA) and norepinephrine (NE) at the synaptic cleft. These medications are not free from side effects and controversy. Newer effective and safe treatments are needed. S Adenosyl-L-methionine (SAM), the active form of methionine, acts as a methyl donor and is involved in many metabolic pathways. It has beta adrenergic and DA receptor agonist activity. We have been using oral SAM in a sample of well diagnosed adults with ADHD, residual state (RS) in a 4-week open trial to establish SAM effectiveness and safety and in a 9-week, double-blind, placebo controlled crossover trial. Preliminary data from the open trial reveal that 75 percent (6 out of 8 male) patients improve on it. The 2 who did not improve had not improved on methylphenidate trial. Improvement ranged from moderate to marked, with minimal and transient side effects that did not interfere with functioning. PMID- 2236466 TI - Therapeutic levels of valproate for psychosis. AB - Valproic acid was added to the treatment regimens of 21 psychiatric inpatients whose response to antipsychotic medications had been inadequate, and steady-state serum valproate levels were obtained on 15. The 7 patients who had unequivocal positive therapeutic responses to valproate improved at a mean serum level of 68, with a 95 percent confidence interval of 50 to 86. The 8 nonresponders had a mean serum level of 37.5 with a 95 percent confidence interval of 13 to 62. There was a weak relationship between oral dose and serum level. Two patients never reached therapeutic levels in spite of oral daily dosages of 5 g and 6 g respectively. Therapeutic levels could not be reached by 7 patients (47%) who were taking more than 1,250 mg daily. Our results suggest that the therapeutic serum range for seizures is valid for psychiatric patients but that the usual suggested oral dosage is often inadequate. Drug interactions may account for this. PMID- 2236467 TI - Fluphenazine plasma levels and clinical response. AB - We monitored fluphenazine plasma levels in 39 schizophrenic patients who participated in a 2-year double-blind comparison of 5 mg and 25 mg of fluphenazine decanoate (FD) administered every 14 days. We investigated the relationship between log-transformed plasma levels at 3, 6, and 9 months and subsequent psychotic exacerbations with logistic regression and survival analysis. Using logistic regression, the relationship was nonsignificant at 3 months (chi-square = .21, df = 1, p = .65), but significant at 6 months (chi square = 4.38, df = 1, p = .04) and 9 months (chi-square = 8.98, df = 1, p = .003). Using survival analysis with fluphenazine levels as a covariate (Cox models), we also found significant relationships between the fluphenazine plasma level and the risk of exacerbations at 6 months (chi-square = 3.77, df = 1, p = .052) and 9 months (chi-square = 12.21, df = 1, p = .0005), but not at three months (chi-square = 0.87, df = 1, p = .65). These findings suggest that the measurement of fluphenazine plasma levels may be helpful in decision-making about the dosage of FD. PMID- 2236468 TI - Stereotypies and tardive dyskinesia: abnormal movements in autistic children. AB - Baseline stereotypic movements in 224 autistic children were studied as well as their relationship to certain demographic variables and measures of overall symptomatology and severity of illness. Prediction of haloperidol-related dyskinesias with measures of stereotypies and demographic variables was also attempted. Stereotypies were present in at least mild form in most children, with most showing moderate severity. Most stereotypies were in the orofacial area. I.Q. was found to be negatively related to stereotypies. Furthermore, across methods of assessment, severity and frequency of stereotypies were found to be positively related to overall symptomatology and severity of illness. No significant predictors of development of dyskinesias were found. PMID- 2236470 TI - [Psychophysiologic microperspective in the psychotherapy process--a sequential approach of investigation]. AB - To Investigate the interpersonal psychophysiology in the psychotherapeutic process a sequential approach using single case analysis is presented. During 18 psychoanalytic-psychosomatic initial interviews simultaneous recordings of heart periods (IBI) and arrhythmia scores (from ecg) and the psychotherapeutic dialogue were made from 10 patients with cardiac neurosis and their interviewers. The general finding is that therapists were able to forecast those segments better, in which their own physiological activity was involved than the segments of their patients. Consideration is given to the consequences which should be drawn from these results for psychophysiological psychotherapy research. PMID- 2236469 TI - [Bulimia with and without a history of anorexia--variants or entities?]. AB - A group of bulimic women (n = 70) with (n = 23) and without (n = 47) a history of anorexia nervosa has been assessed concerning symptomatology, complaints and personality factors. Demographic variables were controlled for bias. As we had supposed, there was no difference for most of the variables analyzed. Some of the residual differences could be due to item formulation ("Oral Control"; EAT) or express the slight persisting underweight ("weight", "underweight") of the former anorexics. Nevertheless, this group unexpectedly seems to feel not equally disturbed concerning "Ineffectivity" (EDI), "Anancasm" (ANIS) and some personality factors ("Social Orientation", "Aggression", "Sorrows concerning health", "Neuroticism"; FPI-R). The similarity is even more impressive if the scores are seen in relation to population norms (Graph.). On demographic variables except weight both groups seem to be strikingly similar. The relative weight (or "underweight"), which was considered as a possible covariate, did not contribute significantly to most of the dimensions, so that the actual body shape cannot be viewed as significantly influencing personality and eating related factors. From the data analyzed we conclude that there are no reasons to consider bulimia with and without a former anorexia as distinct disorders. PMID- 2236472 TI - [Effect of the stress coping mechanisms of oncologic patients on their physical and psychological state in radiotherapy]. AB - An empiric study was designed to investigate how patients cope with radiotherapy and its secondary effects. Subject of inquiry was the influence of variables such as age, sex and individual strategies of coping with stress on the extent of reported strain. 91 cancer patients (66 female, 25 male) undergoing radiotherapy with different diagnoses but comparable history and duration of disease were interviewed concerning physical complaints and impairment of psychic mood at four times: in the beginning, the middle and the end of a 6-week radiotherapy as well as 3 moths afterwards. Additionally general coping strategies were evaluated in the beginning. Results showed that reported impairment (only within the subgroup: women under 50) correlated significantly (p less than 0.01) with a coping behaviour that could be described as a "retreat and giving up". PMID- 2236471 TI - [Assessment of "coping with disease" in patients with amyotrophic lateral sclerosis (ALS): on the use of an interviewer assessment rating scale]. AB - Theories on "Coping" try to explain which resources people use to master crises and conflict situations. Reactions to challenges of life are considered as "coping strategies". In psychosomatic research, the notion of "coping" serves to describe how patients can handle physical or mental illness. Myatrophic (or amyothrophic) lateral sclerosis (ALS) is a rare chronic progressive disease of the nervous system with a gradual loss of motor neurons, resulting in muscular atrophy, weakness and spasticity. Since the etiology is unknown and no curative treatment available, most patients die from respiratory failure within a few years. In a follow-up study on physical disability, medical care and social support in 21 patients with advanced ALS, we tried to address the question how patients get along with such a threatening condition. After semi-standardized clinical interviews with patients and close relatives, two investigators gave independent descriptions of reported or observed "coping strategies" (rated as "not at all-barely-possibly-probably-very probably present"). Considering 17 patients assessed by both raters, significant agreement (Kendall's W) was achieved in three patients only. A comparison of aggregated answers (chi 2-Test) revealed different response sets, since one rater tended to choose extreme scale points, while the other preferred undecided answers. Differences of mean scores were observed in 8 out of 21 items, while significant correlations between investigators were obtained in another 8, including, though, only 2 of those 5 items which both had rated as "probably present" in no less than 50% of the patient sample ("Dejection & Flight-Brooding-Keeping the Situation Open Distraction-Self-Isolation").(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236473 TI - [Daily stress, coping with stress and metabolic control in insulin dependent adult diabetics]. AB - In accordance with previous research investigating adult insulin-dependent diabetics the present study supports evidence for a weak correlation between psychosocial stress and metabolic control (HbA1c). This relation, however, is becoming more substantial, if specific patterns of stress-reactions are taken into account. This is especially the case for a pattern represented by a short form of the SVF-subscale "emotional irritability" (Janke et al., 1984), and even better by the (inversely scored) FPI-K-scale "calmness" (Fahrenberg et al., 1978). Contrary to our expectations a high amount of emotional irritability was leading to a more favorable metabolic control, especially in the case of high psychosocial stress. It is suggested that positive attention-directed and motivating functions of emotional stress-reactions may in the long run compensate or even exceed their short-lived debilitating metabolic effects. PMID- 2236474 TI - [Psychotherapy of sociopathic and objectively dangerous patients. Psychotherapy of sociopathic patients: prerequisites of the therapist and the environment. Parameters of therapeutic technics]. AB - The author proposes that the environment involved in the treatment of sociopathic patients should not foster splitting mechanisms. Preconditions for the therapy and requirements for the capability of the psychotherapist are discussed, especially his attitudes, the cohesion of his own self and his emotional reactions towards his patients. Two case histories are presented to demonstrate the type and timing of the interventions. The therapeutic modality for the treatment of sociopathic disorders takes into consideration the superego distorsions and the defense mechanisms, specially acting out, regression and splitting. PMID- 2236475 TI - Asian rickets and osteomalacia. PMID- 2236476 TI - Factors determining success and energy requirements for cardioversion of atrial fibrillation. AB - Factors thought to affect the success of and energy requirements for cardioversion of atrial fibrillation were studied in 80 (49 male, 31 female) patients aged 21-88 (mean 61.5 years). Transthoracic impedance was measured in advance of the countershock using a 30 kHz low amplitude AC current passed through self-adhesive ECG/defibrillator pads (diameters 8-12 cm) applied to the chest in the antero-posterior (AP) position in 57 patients and the anteroapical (AA) position in 23 patients. Mean transthoracic impedance for all patients was 69.3 +/- 16 (SD) ohms (range 39-131 ohms), but transthoracic impedance was significantly greater in the AA than the AP position (75.4 +/- 13 vs. 66.7 +/- 16 ohms, p = 0.02). Initial energy was 50 J (delivered) and was gradually increased to a maximum of 360 J if required. Cardioversion was successful in 73 of 80 (91.2 per cent), and low energy shocks (less than or equal to 200 J) were successful in 45 of 80 (56.2 per cent) patients. Using single factor analysis, sex, left atrial enlargement, electrode pad positions, aetiology of atrial fibrillation, presence of left ventricular failure, and prior treatment with verapamil or beta adrenergic blockers were not significant determinants of cardioversion success or success of low energy shocks but prior treatment with digoxin was, both for cardioversion success and success at low energies. In patients with transthoracic impedance less than or equal to 70 ohms, low energy shocks were more often successful (33 or 50, 66 per cent) than in patients with transthoracic impedance greater than 70 ohms (12 of 30, 40 per cent), p = 0.04. Using univariate analysis, cardioversion success with low energy shocks was not only significantly associated with prior treatment with digoxin but also with the duration of atrial fibrillation (24 hours to one month and one month to three years) and for shocks of less than or equal to 100 J, with prior treatment with amiodarone. Multifactorial linear regression analysis selected, in rank order, only duration of atrial fibrillation of 24 hours to less than one month and one month to three years as significant predictors of both cardioversion success irrespective of shock strength, and success of low energy shocks. PMID- 2236478 TI - Clinical judgment analysis. AB - Judgement is central to the practice of medicine and occurs between making clinical observations and taking clinical decisions. Clinical judgment analysis has developed as a method of making statistically firm models of doctors' judgments. Computed models reveal the differential importance attached to items of clinical, social, or other data which are determinants of clinical decisions. These models can both reveal the causes of conflicts of judgment and may help resolve them in a way that unaided discussion cannot. Revealing experts' models to students speeds learning of diagnostic skills. Clinical judgment analysis offers a method of probing the judgments not just of students and doctors but also of patients who have shown systematic differences in their perceptions of risk and benefit. The power and relevance of clinical trials can be improved by the consistent application of judgment policies generated from both the trialists and those who will use their results. PMID- 2236477 TI - Adrenal dysfunction in patients with renal amyloid. AB - Amyloidosis is a multi-system disease. Renal involvement often leads to end-stage renal failure, which carries a poor prognosis. This paper reports the adrenal status of 22 patients with renal amyloid who were considered for or who had been commenced on renal replacement therapy. Twelve patients were considered or found to have AA amyloid and the remaining 10 had AL amyloid. Of 16 patients tested, seven demonstrated an abnormal response to a synacthen test. Four patients died at Addisonian crisis and hypo-adrenalism probably contributed to the deaths of a further two patients. Amyloid deposition was found in the adrenal glands in seven patients who died of systemic amyloidosis and renal failure. It is recommended that all patients with renal amyloid should have an assessment of adrenal function performed and if abnormal replacement steroid therapy should be commenced. PMID- 2236479 TI - Long-term results following 131I treatment for Graves' disease in Hong Kong Chinese--discriminant factors predicting hypothyroidism. AB - The clinical outcome of 1028 Hong Kong Chinese patients with Graves' disease treated with radioiodine therapy and followed for a mean of 9.85 +/- 4.84 years (range 2-20) was analysed. Retreatment was required by 413 patients (40.2 per cent), with 134 patients (13.0 per cent) requiring more than two 131I doses. One hundred and eighty-nine patients received carbimazole after 131I until euthyroidism was achieved. The cumulative incidence of hypothyroidism at one, five, 10 and 15 years was 9.6 per cent, 31.4 per cent, 53.8 per cent and 65.8 per cent, respectively. The average incidence of hypothyroidism after the first two years was 3.3 per cent per annum. Stepwise logistic regression analysis of pretreatment variables suggested that a combination of adjunctive carbimazole therapy, absence of ophthalmopathy and longer effective half-lives of 131I were of value in predicting which patients were less likely to develop permanent hypothyroidism. However, the probability of accurately predicting permanent hypothyroidism based on the present model was only 60 per cent. We believe that no single pretreatment variable, or combination of variables, predicts long-term hypothyroidism with sufficient confidence to justify the use of a 'formula' approach for prescribing 131I therapy for Graves' disease. PMID- 2236480 TI - Haemostatic changes in the loin pain and haematuria syndrome: secondary to renal vasospasm? AB - Twenty-five patients (seven male, 18 female) were diagnosed as having the loin pain and haematuria syndrome. Presenting symptoms were either loin pain alone or pain associated with macroscopic or microscopic haematuria, and were longstanding, having been present for mean of 9.3 years in males, and 10 years in females. Ten patients described symptoms of passing gravel or renal stones but these were only demonstrated radiologically in two patients. Investigation of all patients showed anatomically normal renal tracts, normal renal function, and no significant proteinuria. Phase-contrast microscopy during episodes of haematuria revealed dysmorphic red cells in all 10 patients studied. Renal biopsies were performed in 20 patients and showed no glomerular pathology, but arteriolar and arterial hyalinosis was seen in 13 of 20 (65 per cent), fibro-elastosis in larger vessels in eight of 20 (40 per cent) and red blood cells in tubules in 13 of 20 (65 per cent) patients. The histological appearance in vessels was similar to that seen in cyclosporin A nephrotoxicity and would be consistent with the hypothesis that regional vasospasm occurs in the cortical circulation. Haematological studies in 22 patients, when compared with age and sex matched controls, showed the presence of circulating platelet aggregates, elevation of plasma beta-thromboglobulin (p less than 0.001), and increased platelet aggregation in response to serotonin and ADP (p less than 0.05 and p less than 0.03, respectively). Plasma concentrations of D dimer (p less than 0.02) and C reactive protein (p less than 0.03) were also significantly elevated in the patient group. There was no deterioration of renal function during a mean observation period of 3.7 years and no patients developed proteinuria. Treatment was largely supportive; seven patients with intractable loin pain underwent surgical denervation with the relief of pain in four. PMID- 2236481 TI - In vitro colony culture and chromosomal studies in hepatic and portal vein thrombosis--possible evidence of an occult myeloproliferative state. AB - We have studied the prevalence of an underlying myeloproliferative state in 20 patients with either hepatic or portal vein thrombosis. Using conventional clinical and laboratory criteria, an underlying myeloproliferative state was identified as the cause of the thrombosis in five patients (25%). A further 10 of the remaining 15 cases were found to have characteristic in vitro bone marrow culture studies and cytogenetic abnormalities suggestive of an underlying myeloproliferative disorder. Although none of these 10 cases have developed overt clinical and laboratory features of such a myeloproliferative disorder after a median observation period of two years, the presence of clonal karyotypic abnormalities in three cases, increased megakaryocyte colony growth in three cases and endogenous erythropoietin independent colony growth of the marrow erythroid progenitors in seven cases, argues strongly in favour of a primary haematological disorder. This has important therapeutic implications, particularly in cases being considered for orthotopic liver transplantation. PMID- 2236482 TI - The management of atypical non-cardiac chest pain. AB - Atypical, non-cardiac chest pain is common and disabling, and often persists despite negative medical investigations. Aetiology is disputed and management is difficult. A multi-causal model in which both psychological and physical factors play a part is helpful; a fundamental factor is continued misinterpretation of minor physical symptoms as evidence of heart disease. We report supportive evidence and describe a psychological treatment derived from the model. In a randomized trial, cognitive behavioural methods were effective in reducing chest pain, disability and use of medication, in patients both with and without psychiatric disorder. The clinical implications are discussed. PMID- 2236483 TI - The ecology and evolution of inducible defenses. AB - Inducible defenses are responses activated through a previous encounter with a consumer or competitor that confer some degree of resistance to subsequent attacks. While the importance of inducible resistance has long been known in host parasite interactions, it is only recently that its importance has emerged in other natural systems. Although the structural defenses produced by invertebrates to their competitors and predators are by no means the same as an immune response triggered by parasites, these responses all share the properties of (1) specificity, (2) amplification and (3) memory. This review discusses the following ecological consequences and evolutionary causes of inducible defenses: (1) Inducible defenses render historical factors important in biological interactions and can affect the probability of individual survival and growth, as well as affect population dynamics of consumers in some circumstances. (2) Although the benefits of inducible defenses are often balanced by fitness costs, including reduced growth, reproductive output and survivorship, the role of costs and benefits in the evolution of inducible defenses is by no means clear. A more integrated approach would involve a multivariate analysis of the role of natural selection on the inducible characters of interest, their norms of reaction and correlated fitness characters. (3) The disproportionate representation of inducible, morphological defenses among clonal organisms may be due to both a higher rate of origination and enhanced selection to maintain these defenses in clonal taxa. (4) Inducible defenses should be most common when reliable cues are available, attacks by biological agents are unpredictable, and the fitness gains of defenses are balanced by the costs. An integrated approach to studying inducible defenses would thus combine mechanistic estimates of costs, population level estimates of defense effectiveness, and genetic estimates of correlations between fitness and inducible characters. This will allow us to estimate rates of evolution in these phenotypically plastic threshold characters. PMID- 2236484 TI - [Basic concept for esthetic complete dentures (1)]. PMID- 2236485 TI - [Swing-lock with milled lock tongue--guide for preparation]. PMID- 2236486 TI - [Limits of manual crown margin formation (1)]. PMID- 2236487 TI - [Clinical use of opal ceramic]. PMID- 2236488 TI - [Children's prostheses--indications and dental technological preparation]. PMID- 2236489 TI - [Introduction of new type of metal-free ceramic system]. PMID- 2236490 TI - Phagocytic and bactericidal activities of leukocytes in whole blood from atomic bomb survivors. AB - This study evaluated the phagocytic and bactericidal activities of peripheral blood leukocytes from Hiroshima and Nagasaki atomic bomb survivors for Staphylococcus aureus. The data were analyzed by multiple linear regression for age, sex, radiation exposure, city of exposure, and neutrophil counts. No significant radiation effect was observed for either blood phagocytic or bactericidal activities. The only significant variable for these functions was the neutrophil count. PMID- 2236491 TI - Exogenous lactate modifies the repair of potentially lethal damage in three human tumor cell lines irradiated in vitro. AB - Lactate is one of several pathophysiological factors accumulating in the micromilieu of tumors under both hypoxic and well-oxygenized conditions, and thus may affect the recovery of irradiated tumor cells in vivo. In the present study, we investigated the effects of postirradiation incubation with exogenous lactate during confluent holding recovery on the repair of potentially lethal damage in three human tumor cell lines. Recovery was either unaffected or enhanced by low concentrations of exogenous lactate (2-5 mM), whereas it was suppressed by higher concentrations (10-50 mM). With high concentrations, survival in all three cell lines was lower at the end of the confluent holding period than at the beginning, yielding recovery ratios of less than 1.0. The effects differed quantitatively among the three tumor cell lines, and between the tumor cells and the normal diploid fibroblasts (AG 1522) studied previously. PMID- 2236492 TI - Drug sensitivity of heat-resistant mouse B16 melanoma variants. AB - Induction of transient thermotolerance by heat or other cytotoxic stressors has been reported to confer a moderate degree of drug resistance to tumor cells in vitro. In this study, a genetically stable, heat-resistant mouse B16 melanoma variant (W-H75) was tested for its sensitivity to various cytotoxic and antiproliferative agents. The heat-resistant W-H75 cells displayed a moderate two to threefold resistance to doxorubicin, VP-16, VM-26, colchicine, cis dichlorodiammineplatinum(II), HgCl2, and CdCl2. Marginal resistance to 4'(9 acridinylamino)methanesulfon-m-anisidide vinblastine, 1,3-bis(2-chloroethyl)-1 nitro-sourea, and NaAsO2 was observed, while no difference in sensitivity to the anticancer drugs, actinomycin D and camptothecin, was observed. Although W-H75 cells were generally more resistant than the parental cells to most of the agents that were tested, they were collaterally sensitive to the antimetabolites methotrexate and 6-mercaptopurine. Resistance of the W-H75 cells to epipodophyllotoxins and anthracyclines was not due to differences in steady-state drug accumulation. For the epipodophyllotoxin VP-16, resistance may be related to a relative decrease in the number of drug-induced DNA strand breaks in W-H75 cells. However, no difference in DNA strand breakage was observed between W-H75 and parental cells which were treated with doxorubicin, suggesting that resistance to this drug occurred by a different mechanism. The possible involvement of glutathione and glutathione S-transferase in resistance was also investigated. The glutathione content in W-H75 cells was 35% higher than that in the parental line. However, glutathione S-transferase activity appeared to be identical in both cell lines. Two other heat-resistant B16 melanoma variants, B H103 and R-H92, were also tested for sensitivity to doxorubicin and VP-16. In contrast to the W-H75 cells, these two heat-resistant variants were hypersensitive to doxorubicin. The B-H103 cells were also hypersensitive to VP 16. This study suggests that selection for cellular resistance to heat may result in cells that have an altered sensitivity to drugs. PMID- 2236493 TI - The persistence of lymphocytes with dicentric chromosomes following whole-body X irradiation of mice. AB - Thirty-six male C57B1/6 mice were X-irradiated whole body with 3 Gy to generate lymphocytes with dicentric chromosomes to study the persistence of these lymphocytes in the spleen and peripheral blood to estimate the life span of mature B- and T-cells. Peripheral blood and spleen were removed from groups of four mice immediately after radiation exposure and on Days 1, 3, 7, 14, 28, 56, and 112 thereafter. Peripheral blood lymphocytes were cultured with phytohemagglutinin to stimulate T-cell division, and splenic lymphocytes were cultured with either lipopolysaccharide or phytohemagglutinin to stimulate B- or T-cell division, respectively. The initial frequencies of dicentric chromosomes with accompanying fragments observed in splenic T-cells (0.44), splenic B-cells (0.43), and peripheral blood lymphocyte cultures (0.48) initiated on Day 0 were not significantly different. For both splenic and peripheral blood T-lymphocytes, the frequency of cells containing dicentric chromosomes declined in an exponential manner following irradiation, with a 50% reduction in frequency occurring 14 days after exposure. In contrast, the frequency of B-cells containing dicentric chromosomes remained stable through Day 7 but then declined precipitously between Day 7 and Day 14 and remained relatively stable, although slightly above baseline, through Day 112 post-exposure. For both B- and T-cells, less than 5% of the cells contained a dicentric chromosome with accompanying fragments at Day 112. These data indicate that B- and T-lymphocytes with dicentric chromosomes show different decay kinetics and suggest that they may possess different life spans. PMID- 2236494 TI - The effects of X irradiation on the metamorphosis and budding of Aurelia aurita. AB - With the aid of the Aurelia metamorphosis test system, the acute and subtle developmental and behavioral effects of X irradiation in the presence and absence of thyroxine on the Norfolk Aurelia aurita were described. Radiation doses were 0 (control), 50, 100, 150, 200, and 400 Gy. Morphology of the ephyrae, and statolith and rhopalia numbers were recorded using the light microscope. Developmental abnormalities of the polyps and ephyrae were recorded with the scanning electron microscope and light microscope. Major findings from this investigation were the absence of rhopalia and statoliths in ephyrae at 150 and 200 Gy, a reduction in pulses per minute in the ephyrae at 100, 150, and 200 Gy, a reduction in ephyrae released at 150, 200, and 400 Gy, and the development of polyp monsters. There was a significantly higher frequency of polyp monsters in the group exposed to thyroxine prior to radiation than in the thyroxine-free group prior to radiation. PMID- 2236495 TI - Affinity isolation of heat-shock and other calmodulin-binding proteins following hyperthermia. AB - The interaction of calmodulin (CaM) with heat-shock and other binding proteins was studied in rat adenocarcinoma cells. Cells were equilibrium-labeled for 48 h prior to heating for 1 h at 43 degrees C, or pulse-labeled for 2 h at 37 degrees C after heating, to monitor the effect of heat on the affinity of CaM-binding proteins synthesized under these conditions. A CaM antagonist shown to sensitize to heat killing, W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], was used in competition assays to help monitor any changes in affinity. We found that heating tended to reduce the CaM-binding of proteins synthesized before heating relative to their 37 degrees C controls and proteins synthesized after heating tended to have increased binding relative to their respective controls. Members of the heat-shock protein (hsp) 90-, 70-, and 26-kDa families were among the proteins that bound to CaM and were eluted by W-7. The peak elution fractions for the hsp's and other cellular proteins varied, but hsp-70 eluted in the early fractions. The hsp-70 family was also found to be among a number of W-7-binding proteins. We conclude that the assumption that CaM antagonists potentiate killing of heated cells solely by competing nonspecifically for CaM-binding protein sites on CaM does not explain the process completely. These antagonists could also act by competing for CaM-binding sites with specific proteins whose interaction with CaM is important for survival following heating, or by directly binding to other proteins whose function is important for survival and inhibiting their activity. We do not have sufficient data to discern the predominant mechanism among these possibilities, but we believe all are likely to occur in heated cells and speculate that inhibition of the functions of the hsp-70 family is important in several of these antagonist actions. PMID- 2236496 TI - Homologous recombination and mutagenesis of gamma-irradiated plasmid DNA in Escherichia coli host cells. AB - Plasmid DNA was used to study gamma-radiation-induced recombination and mutagenesis in Escherichia coli host cells. Plasmid pBRP1, a derivative of pBR322 containing the lac operon of E. coli, was irradiated with 60Co gamma rays prior to transformation into E. coli strains of different recA and lac genotypes. Plasmid-chromosome recombination was assayed in lacY1 host cells, whereas plasmid mutagenesis was assayed in delta lac host cells lacking chromosomal sequences homologous to the plasmid. Both recombinant and mutant plasmids were identified by the phenotypic changes in lactose utilization, and confirmed by restriction analysis of isolated plasmids. Plasmid-chromosome recombination was induced to high levels (about 20% of survivors at 700 Gy) and was dependent on the host recA gene. Plasmid mutagenesis occurred at lower levels (about 1.5% of survivors at 600 Gy) and was relatively independent of the recA gene. Plasmid survival was unaffected by the presence or absence of host recA mutations or the potential for plasmid-chromosome recombination. PMID- 2236497 TI - Repetitive pulsed-train "off" duration mitigates reductions in root growth rates of Pisum sativum L. induced by 60-Hz electric field. AB - An investigation was undertaken to define a 60-Hz electric field exposure system which would affect a eukaryotic cell system while mitigating a potential thermal rise. The biological effectiveness of pulsed 60-Hz electric fields on a cell system of defined sensitivity to continuous-wave 60-Hz electric fields was sought. Roots of garden pea (Pisum sativum L.) were exposed to pulsed trains of 60-Hz, 430 V/m electric fields. The "on" time was constant at 1 s and the "off" time varied. The repetitive on:off regimens used were 1:20, 1:50, 1:100, 1:130, 1:200, and 1:300. With continuous or 1:20 pulsed fields the growth response was equivalent (representing a 60% depression in root growth rate). The severity of the growth effect diminished as the off time increased; for the 1:100 regimen, the relative growth rate was depressed by about 30%; for the 1:300 regimen, the relative growth rate was equal to that of the controls. PMID- 2236498 TI - Radioprotective effects of dimethyl sulfoxide in golden hamster embryo cells exposed to gamma rays at 77 K. II. Protection from lethal, chromosomal, and DNA damage. AB - Golden hamster embryo cells were exposed to 137Cs gamma rays in the presence or absence of dimethyl sulfoxide at both 310 and 77 K. Dimethyl sulfoxide gave significant protection against cell killing at both 310 and 77 K. The extent of radioprotection with 1.28 M dimethyl sulfoxide at 77 K was 85-89% of the lethal effects observed in the absence of dimethyl sulfoxide at 310 K; the dose modifying factor was 5.7. Dimethyl sulfoxide also exerted protected against gamma ray-induced DNA single-strand breaks and chromosomal aberrations with a maximum protection of 80-100% at a dimethyl sulfoxide concentration of 1.28 M at 77 K. At 77 K, H atoms, ion holes, and electrons can migrate through frozen cells but OH radicals cannot diffuse. Thus the protective effects of dimethyl sulfoxide against cell killing, chromosomal aberrations, and DNA single-strand breaks at 77 K may be due to the scavenging of H atoms or other ions, rather than OH radicals. PMID- 2236499 TI - Pathological effects of the radiation protector WR-151327 in mice. AB - The systemic effects of the radiation protective agent, S-3-(3 methylaminopropylamino) propylphosphorothioic acid (WR-151327), were studied in unirradiated B6CF1 male mice. Fifty mice were injected intraperitoneally with 540 mg/kg WR-151327, and groups of five mice were sacrificed at 14-day intervals up to and including 140 days post-treatment. Ten mice served as sham-injected controls. A necropsy was performed and gross morphological abnormalities were noted. Tissues (brain, eyes, harderian gland, salivary glands, sternal bone marrow, thyroid, lung, thymus, esophagus, trachea, skeletal muscle, heart, liver, kidney, adrenal gland, spleen, small intestine, pancreas, and testes) were fixed in 10% formalin, embedded in paraffin, and sectioned. Slides were routinely stained with hematoxylin and eosin while Alizarin red stain was used to test specifically for the presence of calcium salts. Histopathological effects of WR 151327 were restricted to the testes, salivary gland, and pancreas. The caudal pole of the testes was observed to undergo progressive changes from coagulation necrosis to dystrophic calcification. The cells of the submandibular salivary gland showed mainly hyperchromatic nuclei while the pancreas showed enlarged islets of Langerhans. PMID- 2236500 TI - Repair of radiation-induced DNA damage in thermotolerant and nonthermotolerant HeLa cells. AB - The effect of heat exposure on the repair of radiation-induced DNA damage which inhibits the ability of nuclear DNA to undergo supercoiling changes was studied using the fluorescent halo assay in thermotolerant and nonthermotolerant (normal) cells. The assay utilizes an intercalating, fluorescent dye to unwind and rewind endogenous DNA supercoils. When HeLa cells are exposed to 17.3 Gy radiation the ability of DNA to be rewound into supercoils is completely inhibited. However, the ability of DNA to rewind is 70% restored by 30 min after irradiation. Both thermotolerant and normal cells exposed to 45 degrees C for 30 min prior to irradiation had a rewinding ability intermediate between control and unheated cells, but there was no restoration of rewinding ability up to 3 h postirradiation. Thus, when irradiation immediately followed heating, there was no difference between thermotolerant and normal cells. However, when various time intervals were imposed between heating and irradiation, a difference in the ability of the cells to recover from heat-induced alterations became apparent. In normal cells after 6 h of postheat incubation the cells' ability to restore DNA supercoiling was approximately the same as that of control cells, while in thermotolerant cells only 2 h was required to repair the ability to restore supercoiling at the same rate. The rate of repair of DNA remained correlated with relative nuclear protein content as measured by fluorescein isothiocyanate staining in both thermotolerant and normal cells, indicating a possible relationship between the two. PMID- 2236501 TI - Measured intake and excretion patterns of naturally occurring 234U, 238U, and calcium in humans. AB - The normal dietary and fluid intake and urinary and fecal excretion of 234U and 238U were determined in humans under strictly controlled conditions in the Metabolic Research Ward at Hines Hospital. These values formed the basis of the metabolic balances of these uranium isotopes. The major pathway of 234U and of 238U excretion was via the intestine while the urinary 234U and 238U were very low, averaging 2% of the total excretion. The uranium balances were roughly in equilibrium. These data were used in combination with measurements of tissue concentrations of uranium from nonoccupationally exposed humans to calculate steady-state uptake factors for environmental exposure to uranium isotopes during baseline conditions of a normal dietary intake. PMID- 2236502 TI - Radiosensitivity of human natural killer cells: binding and cytotoxic activities of natural killer cell subsets. AB - The sensitivity of human natural killer (NK) cell activities (both binding and killing) after exposure of peripheral blood mononuclear cells to different doses of gamma radiation was studied. A panel of monoclonal antibodies was used to identify the NK and T-lymphocyte subsets and to evaluate their radiosensitivity. Peripheral blood mononuclear cells were irradiated with low (2-6 Gy) and high (10 30 Gy) doses and NK cell binding and cytotoxic activity against K562 target cells were studied after 3 h and 48 h in culture. The primary damage to NK cell activity was identified at the postbinding level and affected mainly the lytic machinery. After 48 h culture postirradiation, an overall depression of cytotoxic activity was observed, but ionizing radiation produced either a selection of the more cytotoxic NK cell subsets, which therefore might be considered more resistant to radiation damage than the less cytotoxic NK cells, or a long-term stimulation of cytotoxic activity in surviving cells. PMID- 2236503 TI - 75 years of radiological research. PMID- 2236504 TI - 75th anniversary for the Center for Radiological Research. PMID- 2236505 TI - Microdosimetry and Katz's track structure theory. I. One-hit detectors. AB - A microdosimetric treatment of the response of one-hit detectors to radiation is formulated and compared with the model proposed by R. Katz, S. C. Sharma, and M. Homayoonfar (in Topics in Radiation Dosimetry, Suppl. I (F. H. Attix, Ed.), pp. 317-383, Academic Press, New York, 1972) within the framework of their track structure theory. It is shown that radial dose distributions (on which the track structure theory is based) are generally poor substitutes for the exact microdosimetric distributions except when (a) the target is much larger than the radial extent of the track or (b) the "effective" specific energy in the target (alpha z, see text) is negligibly small. Since neither one of these conditions is generally satisfied, it is suggested that a meaningful search for one-hit detectors be based on a microdosimetric description of the stochastics of energy deposition. An analysis of the phi x-174 bacteriophage inactivation data is presented. PMID- 2236506 TI - Influence of microdosimetric quantities on observed dose-response relationships in radiation therapy. AB - The steepness of dose-response curves in radiation therapy depends to a large extent on the statistics of cell killing. This is so if the last few clonogenic tumor cells have to be hit or eradicated by other means to cure the patient. The steepness is dependent on the number of clonogenic cells in the tumor and the possible variation in their sensitivity. However, the uniformity of the dose distribution is also important and a decreased slope may result when the delivery of the dose is nonuniform or statistically uncertain. The variance in the energy imparted at the microdosimetric level to individual cell nuclei constitutes the ultimate limit of the variance in delivered dose at a given mean tumor dose. Considering all dosimetric variances it is shown that for low-LET beams the conventional microdosimetric variance will dominate, while in neutron and high LET beams in general the microdosimetric variance may contribute significantly to the observed dose-response relationship. As a result the normalized slope of the dose-response curve for tumor control and normal tissue complications with neutrons and other high-LET beams will be reduced compared to that with photons. This conclusion is found to be in quantitative agreement with available data from clinical trials with neutron therapy. Finally, it is pointed out that for beams with a very high RBE and LET it may be favorable to deliver a fraction of the total dose in the form of conventional low-LET radiation. This addition of low LET radiation may be desirable to ensure a dose to all clonogenic tumor cell nuclei that is sufficiently high and uniform to achieve a high probability of tumor control. PMID- 2236507 TI - Track structure, lesion development, and cell survival. AB - A stochastic track-structure-dependent model is presented based on DNA double strand breaks (DSBs) interacting in a time- and distance-dependent manner, and in competition with DSB repair, to form exchange-type chromosomal aberrations. Many models of cell survival involve estimation of mean numbers of lesions per cell, which is then related to cell survival. Unless this relationship is linear, this implies that a cell responds not to the number of lesions produced in it, but to the mean number of lesions in all the exposed cells; this is clearly unrealistic, particularly for phenomena such as saturation. In contrast to such deterministic approaches, we describe a stochastic model, in which individual cells are considered and exposed to Monte Carlo-generated tracks of various radiations. The elementary sublesions produced (DSBs) diffuse, repair, or interact, forming lesions (chromosomal exchange-type aberrations) in a time- and distance-dependent manner. Results agree well with experiments for survival of synchronous Chinese hamster V-79 cells exposed to X rays and radiations with LETs from 20 to 170 keV/microns. Thus the main features of survival for low-, medium-, and high-LET radiation are understandable in terms of a single approach, the relative responses to different radiations being determined by their different energy deposition patterns. PMID- 2236508 TI - Dual-function 2-nitroimidazoles as hypoxic cell radiosensitizers and bioreductive cytotoxins: in vivo evaluation in KHT murine sarcomas. AB - The efficacies of a series of potential prodrugs of RSU-1069 and its alkyl aziridine analogues were assessed. These 1-(2-haloethylamino)-3-(2-nitro-1 imidazolyl)-2-propanol compounds were designed to cyclize in vivo to generate 2 nitro-imidazoles with aziridine (RSU-1069) or alkyl-substituted aziridine (RSU 1164, RB-7040, or RSU-1150) functions. Maximum tolerated single, intraperitoneal doses (MTD) were determined in C3H/He mice bearing subcutaneous KHT sarcomas, and a drug dose-response relationship for radiosensitization was established for each compound administered at the optimum time (45-60 min) before local irradiation of tumors with a 10-Gy dose of X-rays. The potentials of the compounds as bioreductive cytotoxins were studied by administering them immediately after irradiation. Tumor cell survival was measured 18-24 h after treatment in an in vitro soft agar clonogenic assay. Results of toxicity, radiosensitization, and bioreductive cytotoxicity assays for each of the prodrugs (RB-6171, RB-6172, RB 6173, RB-6174, and RB-6175) of the alkyl-substituted aziridines were entirely consistent with complete conversion to their respective target compounds. For example, RB-6171 (the prodrug form of RSU-1164) was only about four times less efficient than RSU-1069 as a radiosensitizer and bioreductive cytotoxin but had an MTD 7.5 times higher. In contrast, prodrugs of RSU-1069 (RB-6144 and RB-6145) were two- to threefold less toxic than their expected product. RB-6144 was a poor radiosensitizer and bioreductive agent compared with RSU-1069 and was similar to RB-6170, a nonalkylating nitroimidazole. This is consistent with the observation that there is limited conversion of RB-6144 to RSU-1069 in vitro. However, radiosensitization and bioreductive cytotoxicity produced by RB-6145 were only slightly less than the effects produced by RSU-1069; thus a therapeutic gain was achieved with RB-6145 in a murine tumor model. PMID- 2236509 TI - Studies with bifunctional bioreductive drugs. I. In vitro oncogenic transforming potential. AB - The oncogenic transforming potential of a series of bioreductive drugs including RSU-1069 and its various alkyl-substituted derivatives, RB-7040, RB-88716, RSU 1164, and RB-88712, has been compared using the C3H 10T1/2 cell system. While the aziridine moiety at the terminal end of the side chain confers greater cytotoxicity to both the 2-nitroimidazole (RSU-1069) and the 5-nitrofuran (RB 88716), it also increases the oncogenic transforming potential of the drugs correspondingly. By substituting the aziridine ring with methyl groups, the cytotoxicity and oncogenicity of these bioreductive drugs decrease in a way that is proportional to the degree of methylation. A clear structure-activity relationship can be demonstrated from these methyl-substituted derivatives such that a tetramethyl-substituent (RB-7040) is much less cytotoxic and oncogenic than a dimethyl-substituent (RSU-1164). RB-7040, which has in vitro and in vivo sensitizing efficiency comparable to the parental compound RSU-1069, is roughly tenfold less cytotoxic and, at concentrations that achieve an in vitro enhancement ratio of 2.9, induces a transforming frequency that is indistinguishable from the spontaneous rate. PMID- 2236510 TI - Microdosimetry at middle age: some old experimental problems and new aspirations. AB - The increasingly wider use of microdosimetry in fields other than pure radiobiological research, especially in "practical" domains such as radiation protection and medical physics, has created a number of new practitioners who are not fully acquainted with many of the experimental pitfalls which beset the aspiring microdosimetrist. This paper attempts to review some of the lesser known experimental obstacles. It also presents first results of measurements of single event spectra at nanometer site sizes, based on the use of a small (0.5 x 0.5 mm) counter. Some observations and a critique of the operation of this counter are also presented. It is shown that the counter produces spectra at 5 nm which can be compared with theoretical predictions grounded on fundamental avalanche theory for a cylindrical counter. PMID- 2236511 TI - Studies with bifunctional bioreductive drugs. II. Cytotoxicity assayed with A-549 lung carcinoma cells of human origin. AB - A lung carcinoma cell line of human origin (A-549) cultured in vitro was used to investigate the cytotoxic effect of a range of bifunctional bioreductive drugs. The drugs tested consisted of nitroimidazoles or nitrofurans with terminal aziridine rings on the side chain and are designated RSU-1069, RSU-1164, RB-7040, RB-88716, and RB-88712. Measurements of the cytotoxicity in air demonstrated that methyl and alkyl addition to the aziridine ring reduced cell killing with progressive substitution of the alkylating moiety. A comparison was made of cytotoxicity in air and hypoxia with cells exposed to drugs for a 4-h period. A direct comparison of the aerobic and hypoxic cytotoxicity of RSU-1069 in human (A 549) and rodent cells (V-79-379A) yielded similar results. The cytotoxicity factors, defined to be the ratio of drug concentrations under aerobic and hypoxic conditions which result in 10% cell survival, were found to be 40, 25, 18, and 8, respectively, for the four agents RSU-1069, RSU-1164, RB-88712, and RB-88716 tested in A-549 cells. It has been suggested that under aerobic conditions the aziridine ring is primarily responsible for aerobic toxicity, whereas under hypoxic conditions, the aziridine moiety combined with a reduced 2-nitro moiety produces a bifunctional agent (I. J. Stratford et al., Br. J. Cancer 53, 339-344, 1986). PMID- 2236512 TI - Micronuclei and clonogenicity following low- and high-dose-rate gamma irradiation of normal human fibroblasts. AB - Plateau-phase human fibroblasts were irradiated at either low dose rate (approximately 0.6 Gy/h) or high dose rate (78 Gy/h) with gamma rays and then released from contact inhibition. The frequency of cells containing micronuclei monitored at daily intervals showed that induction was dependent on both dose and dose rate with a peak incidence at 3 days postirradiation. Cumulative frequency distributions indicated a reduction by a factor of 4 when the dose was delivered chronically as opposed to acutely. Distributions also suggested that micronuclei containing cells persist over days, while the dose responses (different by a factor of 2.8) for both high and low dose rate indicated a plateau, particularly following higher doses at low dose rate. Data were not consistent with this response being due to cell cycle delay. Delayed plating resulted in both a reduced incidence of cells with micronuclei and enhanced survival following high- but not low-dose-rate irradiation, with the response being complete by 6 h. Cell surviving fraction and the fraction of cells with micronuclei were negatively correlated, but the relationships were different between the high- and low-dose rate irradiations. This divergence mitigates against using low-dose-rate responsiveness of the short-term micronucleus assay as an indicator of the initial slope of the acute dose-rate survival curve. PMID- 2236513 TI - The effects of the temporal distribution of dose on oncogenic transformation by neutrons and charged particles of intermediate LET. AB - The effects of dose rate and dose fractionation on high-LET radiation-induced oncogenic transformation of C3H 10T1/2 cells were examined. Cells were irradiated with graded doses of 5.9-MeV monoenergetic neutrons administered either in single acute exposures (30 mGy/min) or extended over an 8-h period at low dose rates (from 0.21 to 1 mGy/min). Although cell survival studies showed no difference in effect with a change in radiation delivery rate, enhancement of oncogenic transformation occurred when the dose rate was reduced. When the neutron dose was divided into three fractions over 8 h, the biological effect was intermediate between that for the acute and that for the low-dose-rate exposures. Further irradiations were made using deuterons with an LET of 40 keV/microns. The dose mean lineal energy was comparable to that measured for the 5.9-MeV monoenergetic neutrons. An inverse dose-rate/fractionation effect for the induction of transformation by high-LET deuterons was observed when the time between each of three fractions for a 0.3-Gy total dose was at least 45 min. No further enhancement was seen for longer dose fractionations, suggesting that very long protracted exposures of high-LET radiation would produce no additional enhancement. PMID- 2236514 TI - The reverse protraction factor in the induction of bone sarcomas in radium-224 patients. AB - More than 50 bone sarcomas have occurred among a collective of about 800 patients who had been injected in Germany after World War II with large activities of radium-224 for the intended treatment of bone tuberculosis and ankylosing spondylitis. In an earlier analysis [H. Spiess and C. W. Mays, in Radiation Carcinogenesis. (C. L. Sanders et al., Eds.) pp. 437-450. USAEC Symposium Series 29, CONF-720505, 1973] it was concluded that, at equal mean absorbed doses in the skeleton, patients with longer exposure time had a higher incidence of bone sarcomas. The previous analysis was based on approximations; in particular, it did not account for the varying times at risk of the individual patients. In view of the implications of a reverse protraction factor for basic considerations in radiation protection, the need was therefore felt to reevaluate the data from the continued follow-up by more rigorous statistical methods. A first step of the analysis demonstrates the existence of the reverse dose-rate effect in terms of a suitably constructed rank-order test. In a second step of the analysis it is concluded that the data are consistent with a linear no-threshold dose dependence under the condition of constant exposure time, while there is a steeper than linear dependence on dose when the exposure times increase proportionally to dose. A maximum likelihood fit of the data is then performed in terms of a proportional hazards model that includes the individual parameters, dose, treatment duration, and age at treatment. The fit indicates proportionality of the tumor rates to mean skeletal dose with an added factor (1 + 0.18.tau), where tau is the treatment time in months. This indicates that a protraction of the injections over 15 months instead of 5 months doubles the risk of bone sarcoma. PMID- 2236515 TI - Hyperthermia studies in polyamine-altered human lung carcinoma cells. AB - The effect of polyamine depletion on the survival response of human lung carcinoma cells (A-549) to acute heating at 45 degrees C and its effect on the induction and decay of thermotolerance were investigated in exponential and plateau-phase cells. A 48-h exposure to 1 mM alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, was used to deplete intracellular levels of putrescine and spermidine. Inhibition of polyamine synthesis had no effect on the survival of exponential cells to heating at 45 degrees C, but slightly enhanced the killing of slowly proliferating plateau phase cells. While DFMO treatment did not inhibit the development of thermotolerance, it caused a reduction in the thermotolerance ratio of exponential cells from 2.6 to 1.80, and from 1.66 to 1.59 in plateau-phase cells. DFMO caused thermotolerance to decay more rapidly in polyamine-depleted cells as well. Flow cytometry demonstrated that DFMO did not alter the cell cycle distribution of plateau-phase cells (i.e., greater than 73% in G1/G0), but caused a block and time-dependent accumulation of exponential cells in G1/G0. The cytostatic properties of DFMO in exponential cells which favor its use with phase specific agents, and its ability to alter the magnitude and decay of thermotolerance in human carcinoma cells suggest a potential role for this nontoxic agent in clinically oriented hyperthermia studies. PMID- 2236516 TI - Alterations in specific and general protein synthesis after heat shock in heat sensitive mutants of CHO cells and their wild-type counterparts. AB - The rates of general and specific protein synthesis were studied in two heat sensitive strains of CHO cells (Harvey and Bedford, Radiat. Res. 113, 526-542, 1988), both of which show a reduced ability to develop thermotolerance following an initial 45 degrees C heat shock. After various labeling periods with [35S]methionine, wild-type and mutant labeled proteins were separated by one- and two-dimensional polyacrylamide gel electrophoresis. Autoradiograms showed differences in levels of synthesis of several proteins after a 45 degrees C heat shock. In particular, these were in the hsp-70 group referred to as hsp-70a, b, and c, having molecular weights of 76, 73, and 72 kDa and isoelectric focusing pH values of 5.7, 5.5, and 5.7, respectively. Of particular note were changes in the hsp-70c region of the autoradiograms. We found that there was perhaps a low level of synthesis of hsp-70c in unheated wild-type cells but none was detectable in the mutant lines. After an isosurvival (approximately 10%) pulse of 45 degrees C heat there was a gradual increase in the synthesis of hsp-70c for wild-type but a smaller increase for the heat-sensitive strain 36 (HS-36) cells. In contrast, for HS-23 cells there was a very large initial increase by 5 to 7 h after the heat pulse and then a rapid decrease to undetectable levels by 11 to 13 h. The inhibition and recovery of general protein synthesis for both mutant and wild type cells was also measured following various heat treatments at 45 degrees C. We observed that inhibition and resumption to a "normal" rate of protein synthesis for HS-23 cells paralleled the same response observed for the wild-type 10B2 cells. In sharp contrast, the time for recovery from the inhibition of protein synthesis for HS-36 cells was severely reduced for all heating times tested. Our results show that the period of delay before resumption of protein synthesis after heating does not always correlate with heat sensitivity or the degree of thermotolerance development. Several explanations for these observations are possible. One is that while synthesis of certain heat-shock proteins may indeed be responsible for the development of thermotolerance, the timing of the synthesis of these proteins in relation to the period of inhibition of general protein synthesis is crucial to such development.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2236517 TI - [The reaction of the heart to radiation. I. State of the knowledge based on animal experimental studies]. AB - The aim of curative tumor therapy is healing without complications. Therefore the avoidance of undesirable side-effects in healthy tissue becomes more important to such a degree as the lifespan can be prolonged by therapy: In this review the experiences to cardiac reactions by ionizing radiations are represented from experiments on animals. The former conception of a marked radioresistance of the heart has to be revised to the hitherto presented investigations. Acute inflammatory reactions and late, often progressive alterations can develop in the heart like in other normal tissue. These late-effects especially are reflected at pericardium, myocardium and vessel system (microvessel system and coronaries) and not rarely cause functional injuries of the tissue. Actual investigations give special attention to pathogenesis of acute radioreaction. It is supposed that their explanation gives a better understanding for the process of independence and progress and with that a possibility for prophylactic or therapeutic measures. PMID- 2236518 TI - Radiobiological dose-response relationships by monitoring the ATP-concentration in L 1210 cells using 31P-NMR-spectroscopy. AB - In conventional radiobiology the survival fraction of cell cultures in the exponential phase is observed by the colony-forming ability, and the linear quadratic model represents an adequate frame of the numerical adaptation. The measurement of the ATP-concentration of L 1210 cells by 31P-NMR-spectroscopy in dependence of the applied radiation dose can also be used to evaluate dose response relationships. In particular, the beta-peak of the ATP is suitable to seize the chronological behavior of the cellular ATP-concentration. An access to RBE of a radiation quality is obtained by monitoring the ATP-concentration, and the combination treatment (irradiation and incubation of cisPlatinum) has also been studied with regard to the question of synergistic interactions. PMID- 2236519 TI - [Does the initial hemoglobin value modify the primary tumor reaction? A study of 264 irradiated bronchial cancers]. AB - In a retrospective investigation the remission rate was determined in roentgen picture for 264 male patients with bronchogenic carcinoma after intensive radiotherapy (target dose 56 Gy). Classification of roentgenologic remission was done in 3 groups (complete, partial, minimal/no remission). For each patient the pretherapeutic haemoglobin value was taken from casebook and clinical relevant limit concentrations for an anaemia were correlated with the classified remissions. The difference of regression frequency between complete and partial remission always can be secured statistically irrespectively of chosen limit, that is the anaemia has a provable influence on roentgenologic tumor reaction. To prove that the tumor value as a third variable is not responsible for that a covariant analysis was done. According to that the corrected mean haemoglobin values were 8.9 mmol/l for complete, 8.1 mmol/l for partial and 7.7 mmol/l for minimal/no remission. These differences of the mean values are significant in Newman-Keuls-test, the relation between initial haemoglobin value and remission type is provable independently of tumor volume. Also for bronchogenic carcinoma with that a dependence could be shown between haemoglobin concentration--and by this the oxygen supply of the tumor--and the reaction of the primary tumor after radiotherapy. From this we deduce the recommendation to treat anaemia before beginning of radiotherapy or to irradiate anaemic patients applying an effective sensitizer. PMID- 2236520 TI - Mitotic figures and pyknotic nuclei and necrotic cells in the mouse jejunum during injury and repair after whole-body gamma irradiation. AB - Radiation induced changes in the crypts of jejunum were studied in adult Swiss albino mice exposed to 4.5 Gy, 9.0 Gy and 12.0 Gy of 60Co gamma rays. Two parameters--mitotic figures and pyknotic nuclei and necrotic cells were studied quantitatively to assess the radiation damage and subsequent recovery. Their number in the crypt section was counted at 6 hours, 1, 2, 4, 6, 8 and 14 days after irradiation. In all the three exposure groups the minimum value for mitotic figures was obtained on day 1 when the pyknotic nuclei and necrotic cells were highest. On day 2 partial recovery was seen in both the parameters studied and by day 8 in mice exposed to 4.5 Gy and by day 14 in mice exposed to 9.0 Gy and recovery was complete. However, in mice exposed to 12.0 Gy no mice survived till the last autopsy interval and the normal values were never attained. PMID- 2236521 TI - Crypt cell population changes in the mouse jejunum during injury and repair after whole-body gamma irradiation. AB - Adult Swiss albino mice were exposed to 4.5 Gy, 9.0 Gy and 12.0 Gy of 60Co gamma rays and post-irradiation variations in the crypt cell population of jejunum were studied. In all the three exposure groups, a significant decrease in cellularity was observed on day 1. With the beginning of recovery crypt cell population tended to increase and gradually approached normal value by day 8 and 14 in mice exposed to 4.5 Gy and 9.0 Gy respectively. In mice exposed to 12.0 Gy normal value was never attained. PMID- 2236522 TI - [The functional efficiency of cardiac pacemakers as affected by ionizing radiation]. AB - Influence of functions of cardiac pace-makers by ionizing radiation are represented, that is characterized in praxis relevant parameters as pulse duration and sensitivity in a special clear manner. For these parameters dose limits were defined in a phantom where tolerance ranges of pace-makers, guaranteed by producer, were over or underdosed. These dose values were different in dependence of installed electronic wiring diagrams. The radioresistance of pace-makers with Lewicki-wiring diagram (MCP 211 L) was higher than those with wiring diagram U 115. Measurings showed that the upper dose limits were greater than the known values with 60Co- and 9-MV-roentgen braking radiation and with that the complete programming and functional capacity of the pace-makers were conserved. The close cooperation of radiologists, physicists, cardiologists and technicians in the implantation clinic guarantees a good care for patients with pace-makers during radiotherapy without complications. PMID- 2236523 TI - [Shielded vaginal applicators for line-shaped 192Ir sources for use in the irradiation of cervix cancer]. AB - The possibility is investigated to use shielded vaginal applicators for "line shaped" 192Ir-sources to irradiate cervical carcinoma. Using segment-shaped absorbers of heavy metal the dose can be reduced in ventro-dorsal direction in area of rectum and bladder with irradiation of cervical carcinoma up to a factor of 2 in dependence of rectum and bladder position. Selecting a suitable source position and source standing time a dose reduction can be realized in cranial direction up to two centimetres from the portio. PMID- 2236524 TI - [Initial experiences with radiation planning of combined teletherapy and brachytherapy of gynecologic tumors using CT tomograms]. AB - Dose distributions of a combination from telecobalt-arc-therapy and afterloading therapy for radiation therapy of gynecological cancers were calculated, using a computer program developed in our institute. Taking as a basis CT-scans the bone structures were taken into consideration like inhomogeneities. Conclusions about the individual dose on sensitive organs into the irradiated area like bladder and rectum become possible. The influence of changing parameters such like distance of axis of arc-therapy can be shown clearly. PMID- 2236525 TI - Interventional radiology of the biliary tract. PMID- 2236526 TI - The history of interventional radiology of the biliary tract. PMID- 2236527 TI - Interventional radiologic alternatives to cholecystectomy. AB - It has been estimated that 20 million people in the United States have gallstone disease. The choice of the optimal management strategy for a patient with symptomatic gallstones in the 1990s will take into account the clinical status of the patient, the characteristics of the gallstones, and the patient's preference. Only patients whose doctors understand the advantages and disadvantages of the newer methods can make properly informed choices. When interventional radiologic alternatives to cholecystectomy are being contemplated, one approach is to first consider the patient's clinical presentation (acute or nonacute) and then their risk of death after cholecystectomy (low or high). Figure 5 shows an algorithmic approach to the management of gallbladder stones based on this concept. This algorithm also can be used as a framework for discussion of treatment options with any individual patient. PMID- 2236528 TI - Interventional radiology of the biliary tract. Transcholecystic intervention. AB - Diagnostic and therapeutic biliary intervention by percutaneous access to the gallbladder is an important new area in interventional radiology. The anatomy of the gallbladder, biliary tree, and surrounding viscera is reviewed in this article as a preliminary to discussion of the diagnostic techniques of aspiration, cholangiography, biopsy, and the therapeutic techniques of gallbladder drainage and cholelithotomy. Recently there has been a bewildering proliferation of procedures aimed at removal, fragmentation, and dissolution of gallbladder stones. Several of these are discussed in this article. Removal of common bile duct stones by percutaneous cholecystostomy also is discussed. PMID- 2236529 TI - Fine caliber cholangioscopy. AB - The miniaturized diameters of endoscopes (miniendoscopes) allow percutaneous access for endoscopic visualization of the extrahepatic and intrahepatic biliary system. Practical aspects of different miniendoscopes in an experimental model are described. Clinically, fine caliber cholangioscopy is helpful in detection of retained biliary stones. Nevertheless, discrimination of benign and malignant stenosis remains difficult, and simultaneous intervention under endoscopic guidance is compromised by the low steerability of the instruments. PMID- 2236530 TI - Interventional gallbladder procedures. AB - Interventional radiologic procedures in the gallbladder are influencing both the diagnosis and therapy of many gallbladder disorders. Current diagnostic and therapeutic percutaneous techniques offer important alternatives for their management. This article highlights the spectrum of interventional radiologic techniques available for gallbladder diseases. PMID- 2236531 TI - Percutaneous balloon dilatation of benign biliary strictures. AB - Percutaneous biliary dilatation is an effective alternative to surgical management of benign biliary strictures that has low morbidity and no reported mortality. Reported success rates for this procedure range from 40% to 90% depending on the size of the series, the type of patient being treated, and the length of follow-up period. The procedure is done in the fluoroscopy suite with an angioplasty balloon catheter. Transhepatic access is most common, but the procedure may be done via existing T-tube tracts or specially created jejunal loops. As the frequency of radical liver surgery such as liver transplant and radical trisegmentectomy rises, so too, the rate of biliary stricture is likely to rise, making percutaneous balloon dilatation an increasingly important tool in the interventional radiologist's armamentarium. PMID- 2236532 TI - Interventional radiology of the biliary tract. Metallic stents. AB - Biliary metallic stents were placed in 18 patients with bile duct obstruction. Six patients received Gianturco stents and 14 Wall-stents. Results of these tests are discussed. PMID- 2236533 TI - Biliary endoprostheses. Plastic versus metal stents. AB - Plastic biliary endoprostheses relieved malignant obstructive jaundice in 80% to 90% of the patients. The comfort of a completely indwelling endoprosthesis should be offered to all palliatively treated tumor patients, and external-internal catheters should be reserved for the minority of patients who return with reoccluded endoprostheses. These patients have bacterial flora that rapidly contaminates the endoprosthesis and causes encrustations and reocclusions. Thus, a second endoprosthesis also would reocclude quickly. The mechanism of reocclusion of plastic and metal endoprostheses is completely different. In plastic endoprostheses, bacterial contamination causes decomposition of the bile and subsequent encrustation. In metal endoprostheses tumor ingrowths between the struts of the stent cause reocclusion. Tumor ingrowths were observed in only 6.5% of metal prostheses with a narrow woven mesh (Wallstent), whereas prostheses with large distances between the struts (Gianturco stent) had ingrowth rates of 19% to 50%. This fact shows that tumor ingrowths can be reduced by narrowing the spaces between the metallic network, and, therefore, improvements in the design of the metal stents should reduce the occlusion rate to or below that of plastic endoprostheses, which currently have a lower encrustation rate. The major advantages of expandable metal prostheses are the relative ease and the minimal trauma of the implantation procedure. The Wallstent endoprosthesis, in particular, can be inserted through a 7-F introducer sheath and offers the chance of single-step placement. The 30-day mortality rate, therefore, was only 5%. This is significantly lower than the 30-day mortality rate after insertion of plastic prostheses (15% to 24%). Even simple external catheter drainage procedures have a higher reported 30-day mortality rate (27%). Expandable metal endoprostheses would be the most useful device if the occlusion rate could be kept under 10% in large series. Increasing the length of the endoprostheses to 10 cm in the expanded state could also improve the long-term patency rates. PMID- 2236534 TI - Intracorporeal biliary lithotripsy. AB - Most bile duct calculi can be removed with standard percutaneous or endoscopic techniques. Very large stones are the most common cause for failure. Intracorporeal lithotripsy, and EHL in particular, can be used safely in either the biliary tree or gallbladder to fragment these large stones and allow percutaneous removal or passage. Intracorporeal EHL requires direct vision to prevent damage to the bile duct mucosa. Intracorporeal laser lithotripsy may offer some safety advantages, but the laser requires much more expensive equipment than intracorporeal EHL. Additional studies are needed to determine the technique that is better in each circumstance. PMID- 2236535 TI - Technical aspects of biliary extracorporeal shock wave lithotripsy. AB - Radiologic imaging procedures play a major role in the evaluation of the potential patient for biliary extracorporeal shock wave lithotripsy, both during the procedure and in follow-up evaluation. The treating physician must have a thorough knowledge of ultrasonography techniques. Lithotripsy requires continual monitoring and frequent reassessment to optimize targeting and fragmentation of the gallstones while maintaining patient comfort. PMID- 2236536 TI - Clinical experience with biliary extracorporeal shock wave lithotripsy. AB - Biliary lithotripsy is a new and important development in the nonsurgical management of gallbladder, cystic duct, and bile duct stones. Most patients do not require general or epidural anesthesia with newer second-generation machines. Patient selection and the use of adjuvant therapy to aid fragment clearance are important issues that are discussed. Results from different centers are compared but few long-term results are yet available, i.e., longer than 18 months. PMID- 2236537 TI - Ablation of the cystic duct and the gallbladder. Experimental basis and initial clinical observations. AB - Bipolar radiofrequency electrocoagulation of the cystic duct by catheter can be performed safely and reproducibly using fluoroscopic control and induces endoluminal scar formation. The scar within the cystic duct forms a reliable barrier between the gallbladder and the biliary system and avoids recanalization of the cystic duct at a later date. Sclerotherapy of the isolated gallbladder with 95% ethanol and 3% STS can be performed without toxic or otherwise adverse effects and is suitable to ablate the porcine gallbladder. Initial clinical trials with this new technique on a small number of patients are promising and have demonstrated that the protocol can be applied safely to humans. The electrocoagulation technique by catheter appears suitable to ablate the human cystic duct. Follow-up evaluation of our first patients is under way and must determine whether our regimen is appropriate to ablate the human gallbladder on a long-term basis. Further development of this new approach may eventually enable definitive nonoperative treatment of cholecystolithiasis in selected patients. PMID- 2236538 TI - Combined radiologic and retrograde endoscopic and biliary interventions. AB - Methods of treating complex biliary duct problems by a team composed of an endoscopist and interventional radiologist are described. These procedures are of two types: Those in which all manipulations are performed through the endoscope and those in which an antegrade transhepatic and a retrograde endoscopic approach are combined. PMID- 2236539 TI - [Digital radiography]. AB - Advantages of digital radiography: Improved low contrast imaging; Image processing capability (on line or post-processing); Lower radiation dose for certain applications ("Dose variation"); Digital storage and data transfer; Only one exposure for different imaging characteristics; Optimised real-time image, "digital fluoroscopy" (DBR); Shorter examination times (DBR); Advantages for technically complicated exposures (intensive care, superpositions in the chest region, pediatry) (DLR); High dynamic range, which eliminates over or under exposure; Real time image processing and display (DBR). Disadvantages of digital radiography; Lower spatial resolution is limiting fine structure (max. theoretical resolution is 31p/mm for 1000 and app. 5 lp/mm for 2000 pixels image matrix); Spatial resolution depends from image intensifier diameter or screen format; Lower SNR (Signal to Noise Ratio) for reduced dose, increased noise impression for edge enhancement; Information losses for monitor camera (DBR) hardcopies; Diagnostic capabilities are reduced by noise and low spatial resolution caused by certain applications (mammography). PMID- 2236540 TI - [Diagnostic radiology--development and aspects]. PMID- 2236541 TI - [Niobium powder--a new x-ray contrast medium for tracheobronchography]. AB - In inhalation tracheobronchography with niobium powder in rabbits and a volunteer (physician), excellent contour bronchograms with detailed imaging of the structure of the mucosa were obtained. With methodically proper application the niobium particles of 20-40 microns do not penetrate into the alveoli and are quickly (within 1-5 days) eliminated from the bronchi. Investigations with mice have shown, that niobium powder is insoluble, does not irritate tissues and is not resorbed. It is also nontoxic. PMID- 2236542 TI - [Air or methylcellulose as a double contrast medium in x-ray studies of the small intestine?]. AB - The value of enteroclysma in comparison to peroral roentgenologic imaging of the small bowel is beyond doubt. For the use of applicable double contrast media we carried out comparative investigations in 118 patients with inflammable diseases of the small bowel. 92 patients were investigated with air and 26 with 1% methylcellulose solution in double contrast. Advantages and shortcomings of both methods are discussed. For the diagnostic results as well as for the application of complementing techniques air seems to be better for double contrast studies than methylcellulose. PMID- 2236543 TI - [Angiodynographic detection of an arteriovenous fistula]. PMID- 2236544 TI - [Quantitative flow determinations in the superior femoral artery and the popliteal artery using angiodynography (color-coded duplex sonography) before and after percutaneous transluminal laser angioplasty]. AB - The primary angiographic PTLA-success correlates with the angiodynographically measured blood flow. 24 hours after the treatment the measured flow values in the AFS and AP allow prognoses: 1. Flow volumes in the AP less than 15 ml/min do not allow successful PLTA-therapy. 2. Slight clinical improvement can be expected for flow values greater than 50 ml/min in the AFS and between 20 and 30 ml/min in the AP. 3. AP-values greater than 30 ml/min correlate in this pilot investigations with an excellent clinical result 4 months after intervention. PMID- 2236545 TI - [Color Doppler sonography versus phlebography--a comparison in cases of suspected deep venous thromboses of the leg]. PMID- 2236546 TI - [The application of 2-dimensional echocardiography to the control of the location of the electrode catheter during endocardial cardiography]. AB - Modern methods for treatment of ventricular tachycardia require the exact knowledge of the position of the electrode catheter during intracardiac electrophysiological investigations. X-ray positioning in several projections facilitates the localisation of tachycardia with an accuracy of 4-8 cm2. From eight cadaver hearts schematic diagrams of the right ventricle for two dimensional echocardiography were derived. Endocardiac ventriculocartography under sonographic control was applied in 27 patients 45 times. With this method we were able to detect the electrode catheter in 42 of 45 (93%) patients effectively. Sonographic control facilitates not only the localisation of tachycardia without radiation burden but also its correlation with anatomic ventricular structure which is not possible by roentgenology. 3 negative results were due to negative echoes. In 3 of 5 cases the fulguration of the ventricular tachycardia focus under echo control was possible. Sonographic check up therefore is predilection method for endocardiac ventricular cardiography and can be recommended. PMID- 2236547 TI - [Magnet systems for magnetic resonance tomography]. AB - In the past fifteen years, Magnetic Resonance Tomography (MRT) has become a valuable tool for medical diagnostics. At the same time, Magnetic Resonance Spectroscopy (MRS) has attracted more and more attention in medical and other related areas of investigations. For both methods it is necessary to provide a magnetic field, which can be generated by resistive magnets, by permanent magnets as well as by superconducting magnets. These three concepts are described and compared together with the advantages of each design and the considerations that must be addressed regarding the planned use and the availability of a suitable site. In addition to the main magnet important additions like gradient and shim coils, aspects of site planning and future problems are discussed. PMID- 2236548 TI - [Recent developments in x-ray luminescent imaging systems]. AB - The paper is a survey on the latest developments in luminescent x-ray imaging systems. Special attention was given to two problems, the reduction of cross-over in screen-film-systems by variation of the spectrum of luminescence and the development of digital storage phosphor systems. Recent developments in the evaluation of x-ray luminescent screens are also discussed. PMID- 2236549 TI - [Difficulty in determining ultrasonic attenuation values from selective echograms]. AB - The value of tomography is beyond all doubt. Custom systems allow the quantitative assessment of topographic and kinetic parameters of various organs and the blood. The assessment of tissue, however, is still qualitative and experimental methods for quantitative tissue characteristics are still expensive. We propose a method, that allows the determination of attenuation coefficients with little technical expense. PMID- 2236550 TI - [The use of imaging techniques in the diagnosis of pancreatic diseases]. AB - The present paper discusses the use of modern imaging procedures in the diagnosis of various pancreatic diseases. Specific examination patterns are referred to their underlying pathological pancreatic processes to allow the best possible interpretation of the results of each technique. At present, magnetic resonance imaging does not play a decisive role in the diagnosis of either pancreatitis or pancreatic tumorous masses. PMID- 2236551 TI - [The diagnostic procedure in pancreatic diseases]. AB - Once a diagnosis of acute pancreatitis is established it is necessary to discriminate between an edematous-interstitial and a necrotizing course of the disease, to determine the extent and location of necroses by contrast-enhanced CT and to detect early infection by ultrasound guided needle aspiration. In chronic pancreatitis it is imperative to ascertain the severity by ERCP, and to use imaging techniques to determine degree of functional impairment and the extent to which the inflammatory process has extended to the peripancreatic tissues by means of imaging techniques. Based on clinical data pancreatic carcinoma can not usually be detected until it is already in a late stage, but it can then be confirmed with great reliability by ERCP, contrast-enhanced CT, tumor marker tests and fine needle aspiration. PMID- 2236552 TI - [The place of ERCP in pancreatic diagnosis. The change caused by sonography and computed tomography]. AB - Based on 1099 endoscopic retrograde cholangiopancreatograms (ERCP), 659 examinations conducted in 1973-1980 prior to the introduction of computed tomography (CT) and 440 performed in 1988-1989, the impact of sonography and CT on ERCP is studied. The availability of CT did not cause any significant change in the frequency of and indications for ERCP. The rate of successful ERCP examinations increased from 73.6% to 92%. Complications occurred in 2.3%, and the mortality rate was 0.4% and was similar in both periods. ERCP was the third imaging procedure, being applied after sonography and CT, in most patients. The diagnostic value of ERCP in pancreatic disease is compared with that of sonography and CT in 116 patients with histologically or clinically proven diagnosis. The sensitivity is 79% for ERCP and 78% for CT. Indeterminate findings were recorded in 11% of the ERCP and 8% of the CT examinations; these rates can be decreased by complementary use of both imaging modalities. PMID- 2236553 TI - [A multiple stenosis syndrome of the visceral arteries following chronic pancreatitis?]. AB - Multiple stenoses and occlusions of visceral arteries are documented by CT and angiographic findings in a case report. The possible etiology of pancreatitis is discussed and the differential diagnosis is outlined. PMID- 2236554 TI - [Focal peliosis of the adult liver in combination with glycogenosis type I (v.Gierke). A case report and review of the recent literature]. AB - Peliosis hepatis is a condition characterized by blood-filled lesions in the liver that can be localized or diffuse in distribution. The predisposing factors for this condition include treatment with anabolic steroids, chemotherapeutic and oral contraceptive agents, catabolic metabolic conditions (e.g., hypoglycemia) and certain immunological disorders. This disease probably represents a non specific immunological response to a variety of noxious agents and has been successfully induced in experimental animals. The increased tendency towards liver rupture following blunt trauma and resuscitation procedures may have important medicolegal consequences. We present a case of peliosis hepatis in a patient with type I glycogen storage disease (von Gierke). PMID- 2236555 TI - [The feasibility of pretherapeutic diagnosis of malignant pharyngeal processes using high-frequency cineradiography]. AB - The differentiation between stage T3 and stage T4 pharyngeal tumors is of crucial importance for the proper therapeutic approach (surgery, surgery with consecutive radio- or radiochemotherapy, chemotherapy). The clinical relevance of the additional information provided by cineradiography was evaluated in combination with the endoscopic and computed tomographic results. We performed static and dynamic pharyngography with mono- and double-contrast-methods in four planes, including pharyngeal distension (Valsalva's and Muller's maneuver) and phonation. For the dynamic study, high-speed cineradiography (35 mm film, 50 frames/s) was used. Twenty-three patients with histologically proven neoplasms were examined. It was determined that surgery was technically feasible in 4 out of 14 patients who were previously presumed to have inoperable tumors. In 2 cases, an extension of the tumor mass was seen by cineradiography (results proven intraoperatively). PMID- 2236556 TI - [Pancreatic pseudocyst? A pseudoaneurysm of the splenic artery]. PMID- 2236557 TI - Nurses sued for "loss" of biopsy tissue. PMID- 2236558 TI - Nurse fails to disclose HIV test results: discrimination issue. Case in point: Leckelt v. Bd. of Com'rs. of Hosp. Dist. No. 1 (909 F. 2d 820--LA (1990)). PMID- 2236559 TI - Legal case briefs for nurses. TX.: nurse challenges Dr: retaliatory discharge; WA: nurses sue hospital & pension plan: ERISA. PMID- 2236560 TI - Pre-op enema perforated colon: Res Ipsa Loquitur. Case in point: Lucas v. St. Frances Cabrini Hospital (562 So. 2d 999--LA (1990)). PMID- 2236561 TI - Topics in cardiac transplantation. IV. PMID- 2236562 TI - Early postoperative care of the cardiac transplantation patient: routine considerations and immunosuppressive therapy. AB - The authors have attempted to outline the current state of the art with respect to the early postoperative management of the cardiac transplant recipient with special attention to immunosuppressive therapies. The commonly used agents, as well as the most successful combination regimens, have been described along with the current levels of expectation regarding rates of rejection and infection. Much has been learned regarding the management of these problems. Much remains to be learned to further decrease the incidence of postoperative infection and rejection and, equally if not more importantly, studies to investigate the etiology of transplant coronary artery disease need to be undertaken such that measures to delay or prevent its occurrence and/or arrest its progression can be instituted. PMID- 2236563 TI - Echocardiographic diagnosis of cardiac allograft rejection. PMID- 2236564 TI - Chest pain with normal coronary anatomy: a review of natural history and possible etiologic factors. PMID- 2236565 TI - Atypical causes of curable renovascular hypertension: a review. PMID- 2236566 TI - Oligosaccharide chains of glycoproteins. PMID- 2236567 TI - Bioactive peptide analogs: in vivo and in vitro production. PMID- 2236568 TI - Computer-assisted structure--antileukemic activity analysis of purines and their aza and deaza analogs. PMID- 2236569 TI - Medicinal chemistry: a support or a driving force in drug research? AB - The foregoing has demonstrated most emphatically the significant and central role which chemistry plays in modern and future drug research. It does not mean to diminish the important role of biology but it does serve to show that chemistry is not merely a support for the needs of biology but is a powerful driving force in itself. The two disciplines are essentially interdependent and each relies on the other for success in drug design, discovery and eventual delivery of a useful medicament to the patient. Finally, the medicinal chemist today is faced with as many if not more formidable challenges in medicinal research as his counterpart of a generation ago. The sciences of genetics, molecular biology, neuro pharmacology and electrophysiology have expanded the knowledge base of cellular function many fold. This new knowledge when coupled with the fundamental role of biochemistry in outlining in chemical terms both normal and abnormal cellular events offers the researcher a much more sophisticated appreciation of the cause of disease states. Knowing which enzymes or receptors are involved is a crucial step towards correcting the malfunctioning cellular conditions. With powerful new methods for determining the three-dimensional structure of molecules and computer graphics which give insight on rational drug design and modification, the medicinal chemist can explore with greater confidence than ever before the road to new drugs. The new biology, the new physical methodology and the computer have enhanced the role of chemistry in modern drug research and have given the medicinal chemist a more profound grasp of cellular aberrations leading to disease. This knowledge is a golden rod in the hands of an imaginative chemist in the search of innovative drugs. PMID- 2236570 TI - Neuroimmune axis as a basis of therapy in Alzheimer's disease. PMID- 2236571 TI - Fungal metabolites and Chinese herbal medicine as immunostimulants. PMID- 2236572 TI - Progress in the chemotherapy of leprosy: status, issues and prospects. PMID- 2236573 TI - Present status of Leishmaniasis. PMID- 2236574 TI - Systemic cancer therapy: four decades of progress and some personal perspectives. PMID- 2236575 TI - The use of quantum chemical methods to study molecular mechanisms of drug action. PMID- 2236576 TI - Polymyositis and dermatomyositis 1990--diagnosis, treatment and prognosis. PMID- 2236577 TI - Microdialysis--theory and application. PMID- 2236578 TI - Neuronal organization and information processing in the wind-sensitive cercal receptor/giant interneurone system of the locus and other orthopteroid insects. PMID- 2236579 TI - From phenomenon to mechanism: an investigational strategy. AB - 1. The author describes an investigational strategy useful in the field of psychopharmacology. 2. This strategy is based on the ability of a multi disciplinary team first to measure significant changes in a behavioral or physiological variable in response to an experimental manipulation. 3. This initial measurement allows investigators to identify a phenomenon but not its underlying mechanism. 4. Study then proceeds to assess the anatomical substratum essential to mediating the physiologic change and receptology. 5. Finally, changes in second messenger mechanisms are determined. 6. Study of the neurobiologic effects of bright light is used as an illustration. PMID- 2236580 TI - Clinical studies of 5-HT function using i.v. L-tryptophan. AB - 1. Preclinical studies reveal that long-term treatment with antidepressant drugs induces significant changes in serotonergic (5-HT) receptor sensitivity. Similarly, clinical studies suggest that brain 5-HT function is abnormal in depression. Of the available methodologies for conducting such clinical studies, the pharmacological challenge strategy has proven particularly useful. 2. I.v. L TRP has emerged as the most frequently used challenge agent in diagnostic and neuropsychopharmacological studies of 5-HT function. I.v. L-TRP increases serum prolactin (PRL) in humans, probably via 5-HT mechanisms. Under carefully standardized conditions, this PRL response to L-TRP appears to be a reasonably sensitive and valid measure of net 5-HT function. 3. The PRL response to L-TRP is blunted in depressed patients compared with healthy controls. Blunting has not been observed in panic disorder, obsessive compulsive disorder, or schizophrenia, although preliminary findings suggest it may occur in bulimia. 4. The PRL response to L-TRP is enhanced by certain classes of thymoleptic drugs (TCAs, MAOIs, 5-HT reuptake inhibitors, lithium) in a differentially time-dependent fashion. So-called "atypical" antidepressants (trazodone, mianserin) and benzodiazepines have no effect. Such findings are generally consistent with preclinical electrophysiological findings. 5. These clinical studies of the PRL response to L-TRP, in conjunction with emerging evidence that experimentally reduced plasma TRP can reverse the therapeutic effects of some antidepressants, suggest that antidepressant drug action may be more accurately conceptualized as 5-HT dependent rather than 5-HT enhancing. The availability of more selective 5 HT-active drugs promises to further clarify 5-HT mechanisms of neuropsychiatric disease and drug action at the clinical level. PMID- 2236581 TI - Nimodipine in the treatment of old age dementias. AB - 1. In a multicenter, placebo-controlled, double-blind clinical study in 178 elderly patients with cognitive decline, nimodipine, a calcium antagonist was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with 90 mg of nimodipine administered orally in divided doses for 12 weeks was significantly superior to an inactive placebo on all outcome measures including the Wechsler Memory Scale, the Mini Mental State Examination, the Global Deterioration Scale, the Sandoz Clinical Assessment Geriatric Scale, the Plutchik Geriatric Rating Scale, the Severity of Illness and Global Improvement Scales of Clinical Global Impression, and the Hamilton Psychiatric Rating Scale for Depression. 3. Adverse effects with nimodipine were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment. PMID- 2236582 TI - Influence of protein concentration on platelet 3H-imipramine binding. AB - 1. The effects of protein concentration in the assay mixture on platelet 3H imipramine binding were studied in normal controls. 2. Increasing protein concentrations (76-926 micrograms/ml) were found to alter estimates of binding affinity (Kd) but not the number of binding sites (Bmax). 3. Increasing Kd estimates were protein dependent at concentrations in excess of ca. 200 micrograms/ml but were not protein dependent at lower concentrations. 4. A comparison of the present results with previous reports suggests that widespread interlaboratory differences in reported Bmax values for normal controls cannot be attributed to differences in the protein content of incubated samples. Rather these differences may be due to the inclusion of non-membrane protein in the assayed material. PMID- 2236583 TI - Light-induced plasma melatonin suppression in seasonal affective disorder. AB - 1. Subjects with seasonal affective disorder were exposed to 0, 500 and 1000 lux of white light for one hour beginning at 0300 hours. 2. Plasma samples were taken periodically and analysed for melatonin. 3. Plasma melatonin levels were suppressed by exposure to both 500 and 1000 lux light levels, suggesting that SAD patients show no neuroendocrine insensitivity to light but may show supersensitive responses to light. PMID- 2236584 TI - Treatment of winter depression with a portable, head-mounted phototherapy device. AB - 1. A portable, head-mounted device was developed for administration of light therapy. A randomized crossover protocol was used to test the therapeutic efficacy of this device, compared to a standard light box, for treatment of winter depression. 2. Depressive symptoms were significantly reduced by both the head-mounted device and the light box. 3. Therapeutic efficacy of the two devices was not significantly different. 4. The head-mounted device was rated by patients as significantly more convenient than the conventional light box; this may be important in improving patient compliance. PMID- 2236585 TI - Immobilization 12 days (but not one hour) earlier enhanced 2-deoxy-D-glucose induced immunosuppression: evidence for stressor-induced time-dependent sensitization of the immune system. AB - 1. Prior exposure to a stressor can either increase or decrease subsequent behavioral, neurochemical, and endocrine reactivity to stress, depending on the pattern of stress exposure. 2. Massed or frequent exposures typically induce a reduction in reactivity whereas intermittent or widely spaced exposures increase subsequent reactivity. 3. In the present study, the authors examined whether a single presentation of a temporally remote stressor would increase the immunosuppressive effects of a subsequent stressor. Specifically, the authors investigated the effectiveness of 2-deoxy-D-glucose (2-DG) in suppressing the responsiveness of splenic lymphocytes in male, Sprague-Dawley rats that received either no prior treatment, or immobilization either one hour or 12 days earlier. 4. Splenic lymphocyte responsiveness to the T-cell mitogens, Concanavalin A (Con A) and phytohemagglutinin (PHA) was suppressed following a single injection of 2 DG. 5. The group exposed to the stress of immobilization one hour prior to 2-DG demonstrated a comparable level of immune suppression. 6. In contrast, animals immobilized 12 days prior to the administration of 2-DG showed a more pronounced suppression of immune responsiveness which was significantly greater than the other groups injected with 2-DG. 7. Neither the stress-induced elevation in corticosterone, nor the suppression of blood lymphocyte reactivity to Con-A and PHA was enhanced by prior immobilization. 8. The results indicate that the immunosuppressive effects of an acute stressor can sensitize with the passage of time. PMID- 2236586 TI - Telemetric measurement of core temperature in pharmacological research: validity and reliability. AB - 1. The authors present data establishing the reliability and validity of a method for telemetrically measuring core temperature. 2. The method is designed to be of particular utility to psychobiological researchers. PMID- 2236587 TI - Indomethacin prevents increased catecholamine turnover in rat brain following systemic endotoxin challenge. AB - 1. Key features of the acute phase response to infection are replicated by systemic administrations of lipopolysaccharide and may be mediated via the production of lymphokines and cytokines, including interleukin-1. Inhibition of prostaglandin synthesis may attenuate certain features of the acute phase response. 2. In the present study, the effects of systemic administration of the lipopolysaccharide (LPS, 250 micrograms/rat) and interleukin-1 (IL-1, 10 micrograms/rat) on catecholamine metabolism in different brain regions were compared and the effects of indomethacin, a cyclooxygenase inhibitor was determined. 3. The ratio of metabolite to parent amine was used as an index of turnover of catecholamines. 4. In hypothalamus, both epinephrine and norepinephrine concentrations were decreased and their major metabolite, 3 methoxy,4-hydroxyphenylglycol (MHPG), was elevated at 4, 8 and 24 hr following LPS. The major metabolite of dopamine (homovanillic acid, HVA) was increased at 8 hours in striatum, hypothalamus and medulla. LPS increased dopamine turnover at 8 and 24 hr and norepinephrine turnover at 4, 8 and 24 hr. 5. In all regions examined, IL-1 produced effects similar to LPS on amine and metabolite contents and norepinephrine and dopamine turnover. 6. Significantly, co-administration of a single dose of indomethacin (50 mg/kg) completely blocked LPS-induced changes in hypothalamic catecholamines and metabolites and the increase in turnover at 4 and 8 hr. Furthermore, the effects of IL-1 on hypothalamic MHPG content and norepinephrine turnover were also blocked by indomethacin, although the effects of IL-1 on regional catecholamines and HVA content and turnover were either not modified or partially antagonized by indomethacin. 7. The present results suggest that in the rat, activation of noradrenergic, dopaminergic and epinephrine containing neurons in hypothalamus, as well as dopaminergic neurons in other regions is associated with the acute phase response to endotoxin and that synthesis of prostaglandins plays a pivotal role in catecholamine responses in all brain regions examined. PMID- 2236589 TI - [Crossbridges in contracting muscle captured by rapid freezing]. PMID- 2236588 TI - Decreased alcohol consumption by verapamil in alcohol preferring rats. AB - 1. Calcium channel blockers have been proposed, in addition to inhibiting the influx of Ca++ into the cells, to possess a wide variety of pharmacological effects, including interference with certain neurotransmitters involved in mood, mental disorders and alcohol craving. Further, it has been documented that certain neurotransmitters are involved in alcohol craving both in animals and humans. 2. To investigate the effects of Ca(++)-channel antagonist on alcohol preference, verapamil in three doses (5, 10 and 15 mg/kg) was injected (S.C.) twice daily over a period of one day in alcohol-preferring (P) and alcohol non preferring (NP) rats at 9:00 a.m. and 4:00 p.m. 3. Water, alcohol and food intake were monitored. 4. Our results show that verapamil in doses of 10 and 15 mg/kg significantly (p less than 0.02 and 0.01, respectively) reduced the intake of ethanol and increased the intake of water by P rats. However, injection of an equal volume of saline did not change the pattern of alcohol intake. 5. These results suggest that a (++(+)-channel blocker such as verapamil, could, at least partially, attenuate alcohol preference in alcohol preferring rats. It is possible that verapamil exerts an inhibitory effect on alcohol preference by interfering with Ca++ channels, blocking serotonin uptake or through another mechanism(s). PMID- 2236590 TI - [Cross-bridge movement in heart muscle during contraction]. PMID- 2236591 TI - [Beating of myocardial cells and its regulation--fetal cardiomyocytes]. PMID- 2236592 TI - [Intracellular Ca ion movement in cardiac muscles]. PMID- 2236593 TI - [Regulation of vessel function and its disorder]. PMID- 2236594 TI - [Coronary circulation in physiological and pathological states]. PMID- 2236595 TI - [Energy metabolism and cell injury in ischemic heart]. PMID- 2236596 TI - [Cellular basis of pathophysiology in stunned myocardium]. PMID- 2236597 TI - [Morphological aspects of myocardial necrosis]. PMID- 2236598 TI - [Calcium overload and myocardial injury]. PMID- 2236599 TI - [Role of oxy-radicals in myocardial oxygen paradox]. PMID- 2236600 TI - [Calcium-activated neutral proteases in cell injury]. PMID- 2236601 TI - [Myocardial injury and phospholipases]. PMID- 2236602 TI - [Immunopathogenesis of cardiomyopathy and myocarditis]. PMID- 2236603 TI - [Arrhythmias due to myocardial injury]. PMID- 2236604 TI - [Changes in intracellular anion-concentrations and cardio-active substances]. PMID- 2236605 TI - [Cardiovascular disease and reactive oxygen toxicity--analysis by site-directed SOD derivatives]. PMID- 2236607 TI - [Pathological findings of transplanted heart]. PMID- 2236606 TI - [Myocardial protection during cardiac surgery; cardioplegia]. PMID- 2236608 TI - [Development of new immunosuppressant and experimental cardiac transplantation]. PMID- 2236609 TI - [Organ preservation]. PMID- 2236610 TI - [Liposome chromatography: a new mode of separation using lipid bilayer]. PMID- 2236611 TI - [Ultra-rapid Southern blotting of huge DNA: quantitative and simultaneous transfer method of nucleic acids in size from 0.07 to 2,000 kb]. PMID- 2236612 TI - [Molecular biology of retroviral infection and the associated diseases]. PMID- 2236613 TI - [An overview: what is the embryonic engineering]. PMID- 2236614 TI - [Embryonic engineering]. PMID- 2236615 TI - [Molecular biology of hepatitis B virus]. PMID- 2236616 TI - [Hepatitis B virus and hepatocarcinogenesis]. PMID- 2236617 TI - [Woodchuck hepatitis virus and enhancer]. PMID- 2236618 TI - [Molecular biology of hepatitis delta virus]. PMID- 2236619 TI - [The mechanism of EGF biosynthesis--physiological functions and pathological conditions]. PMID- 2236620 TI - [Cell biological aspects of infectious diseases of human retrovirus: ATL and AIDS]. PMID- 2236621 TI - [A historic, biographic, literary and clinical overview on the 50th anniversary of Freud's treatise, "Time-limited and extended analysis"]. PMID- 2236622 TI - [Prostitution wishes and rescue fantasies--flight from the father. Sketches from the life of a woman ("Anna O."--"P. Berthold"--Bertha Pappenheim)]. AB - Bertha Pappenheim, Breuer's famous patient "Anna O.," was a socially engaged, successful, Jewish women's rights advocate. The details of her biography presented here are not as well known--especially the subsequent course of her illness and treatment and her struggle against prostitution and the white slave trade, the latter carried on with special fascination. All of these show that "Anna O." left Breuer's treatment far from cured and that Bertha was entangled in a lifelong daughter-father conflict. PMID- 2236623 TI - [Dealing with (bypassing) the difference]. AB - The author presents different psychoanalytic conceptualizations of gender difference. She reviews the controversy between Freud and Jones and discusses in detail the views put forward by Montrelay, a student of Lacan, who relates early linguistic development to gender-specific differences in closeness between the child and the "mother's body". PMID- 2236624 TI - [Selected problems of diagnosis, natural course and prognostic significance of borderline arterial hypertension. I. Long-term observations of borderline arterial hypertension in the population of working men]. AB - Of 1236 men, aged 40-59 years, working in the same industrial plant borderline arterial hypertension (BH) was found in 253 (20.5%) subjects. The hypertensives and matched control normotensives (n = 237) were followed up for many years. At 13 years 343 subjects i.e. 70% of the original population were reevaluated. Arterial hypertension developed in 79.1% of the subjects with initial BH, most frequently with systolic++-diastolic, less frequently with systolic and diastolic BH. In normotensives hypertension was diagnosed in 30% of the subjects (p less than 0.001). A negative correlation between blood pressure rise and its initial value was found in all subjects. Out of various risk factors such as overweight, family hypertension, smoking and tachycardia possibly contributing to the development of established hypertension genetic factors and overweight were shown to be predisposing. The results of the studies indicate the need of preventive measures in all men with borderline hypertension and normotensives with family hypertension and overweight. PMID- 2236625 TI - [Evaluation of the effectiveness of hemodialysis using only heparin or prostacyclin with heparin]. AB - In ten patients treated by maintenance hemodialysis due to end-stage renal failure evaluation of dialysis efficiency was performed during the treatment with heparin alone as well as in the course of prostacyclin -heparin infusion. Statistically significant lower level of urea at the end of dialysis and significantly higher urea clearance were found during hemodialysis with prostacyclin -heparin infusion in comparison with infusion of heparin alone. PMID- 2236626 TI - [Bactericidal properties of granulocytes and plasma in patients with rheumatoid arthritis complicated by urinary tract infections]. AB - 26 patients with rheumatoid arthritis complicate by infection of urinary tract, have been decreased bactericidal activity of granulocytes. No changes has been noted in the bactericidal activity of plasma. These results suggested that neutrophils in rheumatoid synovial membrane plays important role of inflammation processes. PMID- 2236627 TI - [Clinical and electrophysiological studies of the organ of hearing in newborn infants. II. Study of maturity of the auditory pathway by brain stem responses (ABR) in newborn infants]. AB - In a group of 130 tested children, 102 of whom a property had evaluated on brain stem responses, we tested the influence of newborn maturation on values of response parameters, their configuration and threshold values. It was shown that newborn maturation lowers in a statistically significant way the threshold values of acoustic stimulus. Also, the configuration of the monitoring changes with age of child tested. Newborn maturation increases the frequency of occurrence of waves II, IV, V and VI though decreases of incidence IV/V complex. In the group of the youngest pre-term babies IV/V complex were present in 50% of cases, whereas in the group of newborns carried to term its present could be verified only in 5-11% of cases. Newborn maturity also influences in an essential way the average latent time consecutive waves as well as central conduction time determined by interpeak latency I-V. Coefficient correlation values for these parameters shows a negative statistical significance correlation. That is, a decreasing of average values of these parameters with maturation of the newborn. It was also shown that structures of the hearing pathway responsible for generation of early and late components of brain stem responses nature at different periods. Peripheral structures of the hearing pathway are significantly more mature at birth than are central structures. PMID- 2236628 TI - [Clinical analysis of 53 cases of septicemia caused by Streptococcus viridans in children]. AB - The clinical analysis has been performed in 53 cases of sepsis induced by Streptococcus viridans. Among children with diagnosis of sepsis majority of cases in group of older infant and children up to 2 year age was due to above infection. The S. viridans strain isolated form the blood were in 90% percentage resistant to cloxacillin , the resistance to penicillin, ampicillin and gentamicin was equal to 70%, 50% and 34% respectively. The main symptoms of the S. viridans sepsis was most frequently localized in lung. Laboratory findings most frequently revealed anemia and toxic granulation in neutrophils . Four children died due to the infection (mortality index to 7.5%). PMID- 2236629 TI - [Proteinuria]. PMID- 2236630 TI - Autobiographical and text recall in the elderly: an investigation of a processing resource deficit. AB - This study examined different explanations of age-related impairments in recall of details from text and autobiographical events. An interpretation of Central Executive Capacity Deficit was supported and explored further. This suggests that details are more demanding of capacity than main points, and that ability to appropriately integrate details with context is likely to be impaired. An implication was that irrelevant and false information may occur, and this was supported in both autobiographical and text recall. The effects were then examined in relation to various measures of ability. The aim was to determine whether declining capacity (as indicated by "Fluid Intelligence" measures) predicted ability to recall in a detailed manner. The difficulty with details was predicted independently by chronological age and by measures of fluid (e.g. AH4 intelligence test) and the more crystallized verbal ability (Mill Hill vocabulary test). Only a measure of the specificity of autobiographical recall was predicted solely by measures of fluid intelligence. Decreased specificity was not a result of faster decay of memory for details, as there was little difference across the lifespan. The resource deficit appears to affect retrieval and appropriate implementation of detail. It was concluded that lower-ability elderly subjects have decreased Central Executive resources, which leads to poor (often inappropriate) integration of details with central thematic points, but that subjects' verbal ability, which does not decline with age, still has an important part to play. PMID- 2236631 TI - Age and prospective memory. AB - This paper reports an investigation into the effects of age, intelligence, and retrospective memory on performance in a prospective memory task in which subjects aged between 52 and 95 were required to telephone once a day either between two times or at an exact time. The most important influence on performance was how subjects chose to remember to make the telephone calls. The best performance was from subjects who telephoned either in conjunction with another routine event or engaged in some form of advanced planning of the daily schedule. The worst performance was from those who relied on internal cues from their own memory. Performance was intermediate from those who used external cues such as notes or diary entries. Subjects in the between condition were less likely to choose internal cues than those in the exact condition, possibly because the task appeared more difficult, and this resulted in their showing superior performance. The effect of age was influenced by the cue used. For subjects using internal cues, those who forgot were older than those who remembered, whereas for subjects using the other cues, those who forgot were younger than those who remembered. Regardless of cue, self-ratings of cognitive failures were related to performance such that those who reported more minor everyday mistakes were indeed more likely to forget to telephone. While there was some indirect effect of general intelligence on performance in the task, there was no relationship between retrospective memory scores and whether or not subjects remembered to telephone. PMID- 2236632 TI - Repetition priming and face processing: priming occurs within the system that responds to the identity of a face. AB - A familiar stimulus that has recently been recognized will be recognized a second time more quickly and more accurately than if it had not been primed by the earlier encounter. This is the phenomenon of "repetition priming". Four experiments on repetition priming of face recognition suggest that repetition priming is a consequence of changes within the system that responds to the familiarity of a stimulus. In Experiment 1, classifying familiar faces by occupation facilitated subsequent responses to the same faces in a familiarity decision task (Is this face familiar or unfamiliar?) but not in an expression decision task (Is this face smiling or unsmiling?) or a sex decision task (Is this face male or female?). In Experiment 2, familiar faces showed repetition priming in a familiarity decision task, regardless of whether a familiarity judgment or an expression judgment had been required when the faces were first encountered. Expression decisions to familiar faces again failed to show repetition priming. In Experiment 3, familiar faces showed repetition priming in a familiarity decision task, regardless of whether a familiarity judgment or a sex judgment had been asked for when the faces were first encountered. Sex decisions to familiar faces again failed to show repetition priming. In Experiment 4, familiarity decisions continued to show repetition priming when a brief presentation time with encouragement to respond while the face was displayed reduced response latencies to speeds comparable to those for sex and expression judgments in Experiments 1 to 3. The results are problematic for theories that propose that repetition priming is mediated by episodic records of previous acts of stimulus encoding. PMID- 2236634 TI - Contextual cueing effects in the remote memory of alcoholic Korsakoff patients and normal subjects. AB - This study examines the effects of contextual cueing on the remote memory of alcoholic Korsakoff patients and normal subjects. Naming of personalities who became famous in each of the five decades beginning 1935 was tested under two conditions: "no-context", in which minimal extraneous cues to identification were provided, and "context", where clear extraneous cues were available. Normal subjects performed better than Korsakoff patients, showed no evidence of a temporal gradient, and exhibited a contextual cueing advantage across all decades. In contrast, Korsakoff patients demonstrated a marked temporal gradient, and the contextual cueing advantage declined systematically as more recent decades were sampled. Further analyses demonstrated that the differential pattern of deficits shown by Korsakoffs and controls was not attributable to absolute differences in performance level. Theoretical implications of these data for explanations of Korsakoff retrograde amnesia are discussed. PMID- 2236633 TI - Episodic memory in dementia of the Alzheimer type and in normal ageing: similar impairment in automatic processing. AB - A perceptual identification task was used to provide an implicit measure for automatic memory processes. The facilitation of word identification on repeated presentation is taken as a measure of the automatic retrieval of an episode. In addition, recognition memory was tested. The recognition task is an explicit test of memory and relies mainly on controlled processing. In the first experiment 11 patients suffering from probable Alzheimer disease and 11 normal age- and sex matched controls were tested. Both groups exhibited a rather small facilitation effect (ca 7%) but did not differ in the size of the effect. However, when tested explicitly, a difference in recognition memory existed between the two groups. In the second experiment the performance of 11 normal young subjects was compared to that of 11 normal elderly subjects. Whereas the elderly group showed a small facilitation effect similar to that observed in the first experiment, a considerable facilitation effect was found for the young group. Also, the elderly group had poorer recognition memory than the young group. PMID- 2236635 TI - The mediation of paired associate recall by representations of properties ascribed to objects in perception and imagination. AB - Any perceived or imagined object will have various properties: for example, it may be of a particular size, shape, and colour. In this paper it is argued that when two objects are perceived or imagined to be interacting, they are likely, as a result, to have properties that may, in part, mediate paired associate recall. In Experiments 1 and 2 it was shown that if the object to be named in recall has properties that are the same as the object named by the cue, then recall is greater than when the properties differ. In Experiment 3 it was shown that if the object to be named in recall has properties that are relevant to a relation between the two objects, then recall is enhanced, as compared with conditions in which this is not the case. In discussion, it is argued that, by means similar to those operating in these experiments, a representation of properties may contribute to recall in experiments in which subjects use interactive imagery. PMID- 2236636 TI - Performance on ratio and interval schedules with matched reinforcement rates. AB - In the first study, rats were trained to pull a chain on a schedule (RPI) that regulates the probability of reinforcement to maintain a constant average reinforcement rate without differentially reinforcing long inter-response times (IRTs). Although the response rate was sensitive to the overall rate of reinforcement, performance was unaffected by variations between 1 and 50 in the IRT memory size used in programming the schedule. In the second study, two groups of animals performed on either a random-interval (RI) schedule or a RPI schedule, with reinforcement rates determined by those generated by a third group performing on a random ratio (RR) 20 schedule. The RI group responded at a lower rate than the RPI group, which, in turn, responded at a lower rate than the RR group, even though the three groups experienced comparable rates of reinforcement. The fact that the RPI group responded at a lower rate than the RR group suggests that the standard response rate difference observed between ratio and interval schedules, which have been matched for reinforcement rate, cannot be attributed solely to the fact that conventional interval schedules differentially reinforce long IRTs. PMID- 2236637 TI - An investigation into blocking of filial imprinting in the chick during exposure to a compound stimulus. AB - The occurrence of "blocking" was investigated in jungle fowl chicks (Gallus gallus spadiceus B.) in an imprinting situation. In Experiment 1, chicks were simultaneously exposed to two stationary coloured cylinders, either two red cylinders (Group RR), a yellow and a red cylinder (YR), or two yellow cylinders (YY). After six days of exposure, the cylinders were removed from the cages and replaced by a yellow and a blue cylinder (i.e. YB) for each chick. This second phase of the experiment lasted for seven days. When the blue cylinder was presented alone during tests at different stages in Phase 2, the RR birds spent significantly more time with this cylinder and emitted fewer shrill calls than the chicks in the YR and YY groups. In Experiment 2, RR and YY birds were reared as in Experiment 1, except that in the second phase of the experiment they were exposed to a blue cylinder only. In this experiment the development of an attachment to the novel blue cylinder proceeded similarly in the RR and YY birds. In Experiment 3, it was found that chicks that were reared with a yellow and a red cylinder preferred the latter stimulus. Thus, although in the first phase of Experiment 1 the RR birds had been exposed to a more attractive stimulus, in tests during the second phase they spent more time with a novel stimulus (B) than the YY birds. These results are consistent with the suggestion that imprinting to a novel stimulus is "blocked" to some extent when that stimulus is presented in compound with another stimulus to which the animal has previously been exposed. PMID- 2236638 TI - Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation. AB - The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterised by alpha/beta values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5 Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2 Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal-tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore necessary to verify further the presented scaling between fraction size and dose rate. PMID- 2236640 TI - Occupational health nursing. PMID- 2236639 TI - Quality assurance in radiotherapy by in vivo dosimetry. 2. Determination of the target absorbed dose. AB - Combined entrance and exit dose measurements were performed with semiconductor detectors on patients, treated for neck and oral cavity malignancies. Transmission measurements showed the important influence of contour inaccuracies and tissue inhomogeneities. In 39.6% (21/53) of the checked contours, the discrepancy between the contour diameter used for routine treatment planning and the actual patient diameter was 1 cm or more, and in this group a systematic tendency for patient diameter underestimation due to the procedure was detected. When the X-ray beam passed through important bone structures such as the mandibular bones or the vertebral body, large discrepancies of 10% and more between the measured and the expected transmission were found. The target absorbed dose was determined from the transmission and entrance dose measurement. A systematic underdosage of about 2% at midline level was found to be due to an inaccuracy in the algorithms of the treatment planning system. Underdosages of 5% or more at midline were detected in more than 20% (47/230) of the measurements. In all cases, the reason for erroneous dose delivery was identified. Entrance dose measurements were previously demonstrated to be useful for the assessment of uncertainties related to treatment machine, patient set-up and treatment planning system (part 1). Transmission measurements (the ratio of the exit to the entrance dose measurement) are shown to be very useful to evaluate uncertainties related to patient data such as contour errors and tissue inhomogeneities as well as to the algorithms of the planning system. The influence of these errors on the target absorbed dose can be estimated and corrections can be applied for each individual patient. PMID- 2236641 TI - A view of occupational health nursing practice: current trends and future prospects. PMID- 2236642 TI - Nursing advances in occupational injury prevention and control. PMID- 2236643 TI - Research in occupational health nursing. PMID- 2236644 TI - The education and training of occupational health nurses: current trends. PMID- 2236645 TI - Annotated bibliography. PMID- 2236646 TI - Twenty years of change and development in occupational health nursing in the UK. PMID- 2236647 TI - Occupational health nursing in developing countries. PMID- 2236648 TI - Holistic health care at the workplace. PMID- 2236649 TI - Communality in a scientific community. PMID- 2236650 TI - Pregnant moments: the process of conception in infertile couples. AB - This report is an explication of the process of conception in infertile couples as illuminated by 24 infertile couples and a comparison group of 6 couples with no fertility impairments. Employing techniques generic to grounded theory research, the investigators found that infertile couples lived conception as a series of biological and phenomenological moments. The process of biomedically assisted conception consisted of three components including: (a) forcing conception; (b) resolving conceptional ambiguity; and (c) reconciling conception as an idea and as an event. The findings suggest the need for a re-examination of current orientations to pregnancy time and space and appraisal of couples' interpretations of conception. In addition, the convergence of the conception experiences of infertile and fertile couples raises questions about the meaning of normal conception in the current technological context of reproduction. PMID- 2236651 TI - Depression, stress, mastery, and social resources in four ethnocultural women's groups. AB - This descriptive study was designed to examine the interrelationships of depression, stress, mastery, and social resources in four ethnocultural women's groups. The random sample (N = 212) was comprised of Chinese (n = 60), Vietnamese (n = 46), Portuguese (n = 56), and Latin American (n = 50) immigrant women. Using the CES-D, high depressive symptoms were reported by all groups. Collectively, the major correlates and predictors of depression were perceived stress and mastery. Group-specific analyses revealed different models for predicting depression in each ethnic group. The findings underscore the need for observation of the indicators of depression in immigrant women--regardless of their phase of resettlement--and a flexible, individualized approach to ethnic women's psychological health care. PMID- 2236652 TI - Factors that contribute to pressure sores in surgical patients. AB - In this prospective study examination was made of whether (a) time on the operating table, (b) proportion of intraoperative diastolic hypotensive episodes, (c) age, (d) preoperative serum albumin, (e) preoperative total protein levels, and (f) preoperative Braden scores could identify those patients who do and do not develop pressure sores during elective surgery. The stratified sample consisted of 125 adult patients. Fifteen patients (12%) developed a total of 23 pressure sores. A discriminant function using time on the operating table, extracorporeal circulation, and age emerged as the best predictor correctly classifying 12 of 15 patients who developed pressure sores and 83 of 110 patients who remained pressure sore free. PMID- 2236653 TI - Self-care agency as a function of patient-environmental factors among nursing home residents. AB - The relationship between environmental and personal factors on self-appraised self-care agency of nursing home residents was examined. Data were collected from 83 nursing home residents in relation to self-care abilities, environmental constraints, and selected demographic factors. Race and previous occupation were related to self-care agency with residents who were black or previously self employed evidencing higher scores. In addition, residents who viewed the home as overly restrictive or fostering dependence had lower perceptions of their self care abilities. The results are discussed in terms of Orem's theory of self-care, social learning theory, and implications for restructuring care within nursing homes. PMID- 2236654 TI - The process of rater training for observational instruments: implications for interrater reliability. AB - Although the process of rater training is important for establishing interrater reliability of observational instruments, there is little information available in current literature to guide the researcher. In this article, principles and procedures that can be used when rater performance is a critical element of reliability assessment are described. Three phases of the process of rater training are presented: (a) training raters to use the instrument; (b) evaluating rater performance at the end of training; and (c) determining the extent to which rater training is maintained during a reliability study. An example is presented to illustrate how these phases were incorporated in a study to examine the reliability of a measure of patient intensity called the Patient Intensity for Nursing Index (PINI). PMID- 2236655 TI - A validity study of four empathy instruments. AB - The construct validity of four empathy instruments were evaluated through examining group differences and correlations between tests. Subjects were 18 registered nurses (RNs) and 32 nursing assistants (NAs). Instruments used were the Empathy Test (Layton, 1979), the Carkhuff (1969a, 1969b) Empathic Understanding in Interpersonal Processes Scale, the empathy subtest of the Barrett-Lennard (1962) Relationship Inventory, and LaMonica's (1981) Empathy Construct Rating Scale (ECRS). The first hypothesis, that RNs would score significantly higher than NAs on all empathy measures, was confirmed (p less than .0003 to p less than .027). The second hypothesis, that the various empathy measures would be positively related, was partially confirmed. The Carkhuff scale was significantly correlated with the ECRS (r = .25, p less than .05). The ECRS and the Barrett-Lennard also were correlated (r = .78, p less than .001). Results are interpreted using Barrett-Lennard's (1981) theory of empathy. PMID- 2236656 TI - Department of Health and Human Services, Public Health Service, National Institutes of Health. Human Gene Therapy Subcommittee, Minutes of Meeting, March 30, 1990. PMID- 2236657 TI - Department of Health and Human Services, National Institutes of Health. Recombinant DNA research: proposed actions under guidelines. PMID- 2236658 TI - Department of Health and Human Services, Public Health Service, National Institutes of Health. Recombinant DNA Advisory Committee, Minutes of meeting, February 5, 1990. PMID- 2236659 TI - The influences of dexamethasone and indomethacin on 67Ga uptake by normal tissues. AB - Dexamethasone (DEX) increased 67Ga uptake by the liver and spleen at 4, 8, and even 24 h after the injection of 67Ga. These results showed that DEX influenced 67Ga accumulation as well as the initial entry of 67Ga in the liver and spleen. On the other hand, indomethacin (IM) decreased 67Ga uptake by the liver and spleen at 4 h after the injection of 67Ga but did not influence the uptake at 8 or 24 h after the injection of 67Ga. Moreover, DEX or IM little influenced 67Ga uptake by the kidney and muscle. These results suggest that the influence of DEX or IM on 67Ga uptake or accumulation is specific for the liver and spleen. PMID- 2236660 TI - [Evaluation of prognosis in patients with old myocardial infarction--using 201Tl myocardial scintigraphy and 99mTc cardiac scintigraphy]. AB - To evaluate the prognosis in 57 patients with old myocardial infarctions, 201Tl myocardial scintigraphy and 99mTc-HSA gated blood pool scan had been done as a 5 year follow up study. We subdivided into two groups; group I (over 60 years) and group II (under 60 years). Cardiac index (CI) and right ventricular ejection fraction (RVEF) did not change significantly, however left ventricular ejection fraction (LVEF) changed significantly (p less than 0.05). Correlationship between CAG score and delta LVEF by handgrip exercise test was y = -1.34 x +3.61 (n = 44, r = -0.400, p less than 0.01). Otherwise, Tl defect ratio between first and final examination did not show the significant change in two groups. In conclusion, nuclear examination (cardiac function and myocardial blood flow) is significant to evaluate the prognosis in patients with myocardial infarction. PMID- 2236661 TI - [Measurement of radiation energy and its application. V. Measurement of gamma-ray energy and its application. (1). Measurement of gamma-ray energy using Ge and NaI(Tl) detectors]. PMID- 2236662 TI - [Investigation on thermal-neutron sensitivity of commercial BeO(Na) thermoluminescence dosimeter and development of thermal-neutron insensitive BeO(Na) phosphors encapsulated in quartz-capillary]. AB - BeO(Na) TLD on the market, UD-170 L, gives thermoluminescence response equivalent to irradiation with 3.2 +/- 0.5 cGy of 60Co gamma-rays after irradiation with 10(10) thermal neutrons per cm2. Because of this neutron sensitivity, UD-170 L is not suitable for measurement of gamma-rays in gamma-neutron mixed radiation from a nuclear reactor of Kinki University when we use it for radiobiological research. To reduce this troublesome sensitivity, we replaced the glass capillary used for UD-170 L with a quartz capillary. Quartz tube encapsulated BeO(Na) showed a markedly reduced response to thermal neutrons. PMID- 2236663 TI - [A new application of bull's-eye analysis to lung perfusion scintigraphy]. AB - Technetium-99m macroaggregated albumin lung perfusion scintigraphy was performed and evaluated semiquantitatively by bull's-eye analysis in 24, including 7 with central pulmonary carcinoma, 3 with hypersensitivity pneumonitis (HP), 3 with diffuse panbronchiolitis (DPB) and 11 normal subjects. First, whole lung field was divided into three regions by three concentric circles. And then radial axes were projected from the center to define 36 sectors, 10 degree each. The counts of each sector was calculated and bull's-eye image and circumferential profile curve were displayed. The patient's map was compared with the lower limit of normal (mean-2 SD), and the extent score (ES) and the severity score (SS) were calculated. The ES was 0.25 +/- 0.12 in pulmonary carcinoma (n = 7), 0.08 +/- 0.07 in HP (n = 3), 0.06 +/- 0.04 in DPB (n = 3). The SS was 26.39 +/- 15.17 in pulmonary carcinoma, 4.75 +/- 5.57 in HP, 4.29 +/- 3.67 in DPB. In one case of central pulmonary carcinoma, segmental perfusion defect was evaluated semiquantitatively by bull's-eye image and circumferential profile curve. And in one case of HP, the change of regional pulmonary blood flow could be followed easily using extent and severity map. This new application of Bull's eye analysis to lung perfusion scintigraphy might be useful to evaluate regional pulmonary blood flow. PMID- 2236664 TI - Immunoradiometric assay for prolactin in serum and tissue--comparison with radioimmunoassay. AB - Prolactin (PRL) concentrations in sera and tumors of patients with various pituitary tumors were measured by both immunoradiometric assay (IRMA) and radioimmunoassay (RIA). PRL concentrations in sera and tumor tissues measured by IRMA were well correlated with those measured by RIA. PRL concentrations in sera reflected those of tumors removed. This IRMA is a simple and useful method for PRL determination in serum and tissue. PMID- 2236665 TI - [Efficiencies of contamination source for flooring and some materials used in unencapsulated radioactivity handling facilities]. AB - The efficiencies of contamination source, defined in ISO Report 7506-1, were experimentally determined for such materials as flooring, polyethylene, smear tested filter paper and stainless steel plate. 5 nuclides of 147Pm, 60Co, 137Cs, 204Tl and 90Sr-Y were used to study beta-ray energy dependence of the efficiency, and 241Am as alpha-ray emitter. The charge-up effect in the measurement by a window-less 2 pi-proportional counter was evaluated to obtain reliable surface emission rate. The measured efficiencies for non-permeable materials, except for two cases, are more than 0.5 even for 147Pm. The ISO recommendations were shown to be conservative enough on the basis of present results. PMID- 2236666 TI - [Solid scintillator "Ready Cap" for measurement with a liquid scintillation counter--spectra and counting efficiencies for 15 different radionuclides]. AB - "Ready Cap", a small plastic container coated with solid scintillator has recently been introduced (Beckman Instruments, Inc.). Pulse height spectra and counting efficiencies obtained with a liquid scintillator and Ready Cap using a liquid scintillator counter were compared for 15 different radionuclides. For radionuclides emitting low-energy beta-rays or characteristic X-rays, the spectra for Ready Cap shifted toward the higher energy side compared with the spectra for the liquid scintillator. This tendency was reversed for the nuclides emitting higher-energy beta-radiations (36Cl and 32P). Generally, counting efficiencies both in Ready Cap and in liquid scintillator increased with increase in the energy of beta- or X-rays. For some nuclides, Ready Cap gave higher counting efficiencies and for others it gave lower values than in the liquid scintillator. However, the differences were not large within each nuclide. The use of Ready Cap is recommended for measurements of radionuclides when liquid scintillation cocktails have no means of waste disposal under the present Japanese radioisotope regulation. PMID- 2236667 TI - [Shielding calculations for bremsstrahlung from beta-emitters]. PMID- 2236668 TI - [Measurement of radiation energy and its application (13). V. Measurement of gamma-ray energy and its application (2). Analyses of gamma-ray spectrum data]. PMID- 2236669 TI - A casebook in psychiatric ethics. Introduction. PMID- 2236670 TI - Valid consent and refusal. PMID- 2236671 TI - Paternalism in psychiatry. PMID- 2236672 TI - Relationships with colleagues. PMID- 2236673 TI - Sexual attraction toward patients. PMID- 2236674 TI - [From the pages of "La Radiologia Medica": nuclear medicine]. PMID- 2236675 TI - [Magnetic resonance in the staging of bladder neoplasms: results of the use of JKA1, a ferrous contrast solution]. AB - The authors report the results of the staging of urinary bladder cancers by means of MRI using a new ferrous contrastographic solution called JKA1. Eighteen patients with proved bladder neoplasms were examined by means of MRI: the bladder was filled with physiological solution first, and then with JKA1. Six patients were studied also after filling their bladders with Gd-DTPA solution (1:50). The results show that the use of JKA1, a T2-positive contrast medium, improved MR capabilities in the evaluation of small lesions (phi less than 1 cm) with minimal invasion of bladder wall; MR staging accuracy was 66.6% with the physiological solution and 77.8% with JKA1. The authors confirm the need for a wider MR study, in particular of T2 lesions (a critical subject for staging and surgical management) to assess MR diagnostic capabilities. PMID- 2236676 TI - [Magnetic resonance angiography of the neck vessels: technique and anatomy]. AB - The authors identified the standard projections for studying neck vessels with magnetic resonance angiography. Sixty volunteers underwent angio-MR of the arterial neck vessels with FISP 3D FT sequences obtained on the coronal and sagittal planes. The gradient-echo sequence (FISP 3D FT) was acquired with TR = 0.04-0.08 s and TE = 15 ms, with 25 degrees flip angle. Single excitated slices of thickness ranging from 1-2 mm were included in the acquisition volume. These sequences were subsequently processed by the maximum intensity projection method. Two radiologists examined our results to choose the optimal projections. We used a semiquantitative scale which allowed us to distinguish 3 different diagnostic levels for each projection: well-visualized vessels, poorly-visualized, and non visualized ones. For each section axial rotations were performed ranging from 0 degree to 180 degrees, with 15 degrees intervals. On the coronal plane, rotations from -45 degrees to 45 degrees were the optimal ones to visualize the studied vessels. The 0 degree-15 degrees-30 degrees-45 degrees-135 degrees-165 degrees 180 degrees projections allowed the common carotids to be clearly demonstrated together with the vertebral arteries. The other projections appeared to be useless for diagnostic purposes. On the sagittal plane, rotations from 60 degrees to 120 degrees were the optimal ones. The 90 degrees projection allowed the demonstration of all the big arterial vessels of the neck, including carotid bifurcation and internal and external carotids. The assessment of the optimal diagnostic projections for angio-MR of the neck vessels is helpful to reduce post processing time. As a matter of fact, the immediate visualization, during the examination, of the standard projections allows further acquisitions to be obtained--if needed--to try to solve specific diagnostic doubts. PMID- 2236677 TI - [Magnetic resonance in the diagnosis of bone infections]. AB - Skeletal infections represent a variety of clinical and pathological conditions in which both an early diagnosis and the precise evaluation of disease extent are very important in planning proper therapy. To determine MRI capabilities and limitations in the evaluation of skeletal infections 21 patients--12 with a clinical diagnosis of osteomyelitis of the lower limbs and 9 with a clinical diagnosis of spondyloscitis--were studied with this technique. All patients were examined with conventional X-rays; conventional tomography was performed in 3 cases, and CT in 6. Signal intensities and morphological aspects were then evaluated with MRI. MRI diagnoses were compared with surgical findings or clinical follow-up, after antibiotic therapy: 19 true-positives were observed, together with 1 true-negative, 1 false-positive, and no false-negatives. MRI findings were correlated with those of conventional radiology: MRI identified the lesions and their nature in 100% of cases, whereas conventional radiology did the same in 85% of cases; in 50% of cases only the latter was able to define the nature of the process. Four patients underwent MRI follow-up. MRI was highly sensitive in determining the presence of lesions in an early stage and in demonstrating lesion regression. Moreover, MRI was able to identify the complications occurring in some cases of osteomyelitis and spondyloscitis. In all cases MRI allowed the extent of the disease to be accurately determined and, in osteomyelitis of the lower limbs, it was extremely useful to differentiate soft tissue infections from bone marrow involvement. PMID- 2236678 TI - [Digital radiography in neonatal intensive care]. AB - The authors report their experience with the routinary use of a computerized digital radiography system in Intensive Neonatal Care department. The conventional screen-film system is replaced by photostimulable imaging plates, which are scanned during processing by a laser providing the digital image. The latter is subsequently processable on high-resolution monitors. Over a 6-month period 86 examinations were performed with this method in Intensive Neonatal Care; good technical results were obtained. The use of digital radiography in intensive neonatal care is extremely promising for it allows high-quality images to be obtained, and radiation dose and number of acquisitions to be reduced. Finally, work stations allow both selective visualization of different body structures and their magnification. PMID- 2236679 TI - [Duplex-sonography in the preoperative evaluation of the small saphenous vein]. AB - The authors analyze the results obtained by means of Doppler US, duplex examination and venography in the preoperative evaluation of venous vascular anatomy and flow dynamics in the popliteal fossa for short saphenous vein surgery. As a whole, 50 legs were examined in 34 patients who subsequently underwent surgery. The confluence of the short saphenous vein in the deep system proved to be very variable. Doppler results were compared with contrastographic ones: Doppler US had 10% accuracy in locating the confluence of the short saphenous vein and the figure rose to 62% with a +/- 2 cm tolerance. Duplex US had 30% and 98%, respectively. The latter always correctly demonstrated the reflux, while Doppler US in 5 cases (10%) ascribed gastrocnemius vein incompetence (4 cases) and Giacomini vein incompetence (1 case) to the short saphenous vein. The above findings demonstrate the total reliability of duplex US versus Doppler US and venography in recognizing the anatomic confluence and in allowing the fluximetric evaluation in a noninvasive, riskless and inexpensive way. PMID- 2236680 TI - [Echographic evaluation of abscess pathology in superficial soft tissue. Personal experience]. AB - Sonography is currently considered a very useful technique for the study of inflammatory-abscess conditions in superficial soft tissues. The authors report their experience with US in the study of 22 patients. In 15 of them a comparison was made with X-ray findings, in 4 with fistulographic and in 2 with CT results. US allows the abscesses to be evaluated in both their morphological structure and anatomical topography. US has proven especially useful in correctly evaluating both complete and incomplete fistulas, as well as in revealing foreign bodies. The US pattern of an abscess often confirms clinical diagnosis for it supplies further and more accurate information. Moreover, US sometimes allows an abscess to be demonstrated even when the latter was missed at clinics. However, the differential diagnosis with malignant neoplasm is difficult and sometimes a decision can be made only by means of other diagnostic imaging modalities. PMID- 2236681 TI - [Synopsis of wrist pathology. Xeroradiography vs digital radiology]. AB - Pathologic conditions of the wrist involve both musculoskeletal structures (bones and joints) and soft tissues, of which fat pads are an important diagnostic aid to recognize various disorders. The authors report their 5-year experience with Xeroradiography in the diagnosis of various pathologic conditions (e.g., inflammatory, degenerative, and tumoral conditions) of the wrist. The importance of Xeroradiography was emphasized, in the past, because of its characteristic technical properties, especially in demonstrating lower-density tissues tumors. The main advantage of Xeroradiography is the physical phenomenon known as edge effect, which increases image contrast at the borders. Other differences between xeroradiography and conventional radiography are: broader recording latitude of the former, together with its higher resolution power (100 lines/mm), and high exposition power (which makes repeats useless). Thus, Xeroradiography allows the contemporary depiction of various and different structures and densities--e.g., bones and soft tissues. Unfortunately, radiation dose to the patient is higher during Xeroradiography than during conventional radiography. That is why digital radiography has nowadays replaced Xeroradiography. In fact, the former provides images that are comparable with those obtained by means of conventional radiography and--sometimes--even with xeroradiographic images. Moreover, the use of digital radiography allows radiation dose to the patient to be markedly reduced, whereas recording latitude remains the same. PMID- 2236683 TI - [Echographic anatomy of the newborn hip and high-resolution equipment: internal capsular stria and perichondrial gap]. AB - The use of high-resolution US equipment in the examination of the newborn hip allowed the evaluation of a thin echogenic stripe (the internal capsular stripe), which defines laterally the acetabular hyaline cartilage. By means of an anatomo histological preparation the echogenic stripe can be related to either the capsular circular fibres or the interface between the latter and the hyaline cartilage. The internal capsular stripe, together with the echogenic synovial stripe, precisely delimit the whole acetabular hyaline cartilage. Furthermore, in many babies high-resolution US sometimes fails to demonstrate Graf's "perichondral gap", so that an accurate anatomic knowledge of the hip becomes necessary in the evaluation of acetabular labrum. PMID- 2236682 TI - [Ultrasonography in the preoperative staging of carcinoma of the breast]. AB - Data relative to 51 patients operated for breast carcinoma were retrospectively reviewed. All patients had undergone US and mammographic evaluation of max diameter of the neoplastic nodule. The above data were correlated with pathologic measurements of the surgical specimens. US-pathologic correlation coefficient was extremely high (r = 0.94). US proved especially helpful in those cases where mammography had failed to visualize the mass-namely in patients with dense breasts. Nearly all evaluated carcinomas had a typical US pattern: a hypoechoic lesion with irregular outline. US is recommended in evaluating tumor response to nonsurgical conservative treatment. PMID- 2236684 TI - [Radiologic changes in the pelvis of patients with chronic renal insufficiency undergoing periodic dialysis]. AB - Bone alterations in the patients undergoing periodic dialysis represent a frequent and invalidating complication and cause the pattern called uremic osteodystrophy. In this study we have examined 173 pelvic X-rays of 73 patients affected with chronic renal insufficiency and undergoing periodic dialysis. The results indicate the presence of all the lesions characterizing uremic osteodystrophy. Arterial calcifications and osteoporosis are the most frequent patterns; with various incidence, osteomalacia, osteitis fibrosa, osteosclerosis and brown tumors are associated. In this group of patients, who were followed for many years, a non-univocal behavior was observed: next to patterns of progressive aggravation, such as vascular calcifications, phases of stabilization/improvement were observed, e.g., in case of brown tumors and osteitis fibrosa. PMID- 2236685 TI - [Echography and cytology in the study of spreading pathology of the salivary glands]. AB - The contribution of the combined use of US and cytology is evaluated in the diagnosis of masses in the salivary glands and adjacent structures. US had 87.2% sensitivity in locating the mass; its accuracy in defining both physical structure and benign/malignant nature of the lesion was 91% and 74%, respectively. Thus US, after demonstrating a lesion, does not always allow the exact definition of its characteristic. In many of these cases, other imaging modalities do not help either. In our series of cases, cytology allowed an unquestionable diagnosis to be made in 87.2% of cases, and the combined use of US and cytology rose the figure to 97%. The only limitation is the evaluation of the deep extent of large masses: in such cases CT or, if available, MR imaging are recommended. PMID- 2236686 TI - [Multicentric reticulohistiocytosis (lipoid dermato-arthritis). A radiologic study of 3 cases]. AB - The authors report their experience with 3 cases of multicentric reticulohistiocytosis observed over 6 years of outpatient radiological practice. The condition presents with the following radiological patterns: 1) clear-cut erosions of the articular surfaces, especially in the distal interphalangeal joints of the hands and in the metatarso-phalangeal joints of the feet, with symmetrical distribution (not necessarily); 2) osteolytic punched-out areas in the epiphyseal spongiosa, ranging in size from 1 mm to over 1 cm; 3) no osteoporosis, no osteo-proliferative or periosteal reactions, not even in the presence of large osteoarticular destructions; 4) frequent atlanto-epistropheal subluxation; 5) articular ankylosis at the sacroiliac joints only. The association of the above patterns and the relatively benign clinical course distinguish multicentric reticulohistiocytosis from rheumatoid arthritis, psoriasis arthritis, erosive osteoarthritis, and gout. A reliable diagnosis can be suggested on the basis of radiological findings alone, even before cutaneous or mucosal lesions appear--which are, at any rate, not sure to appear and typical of nails only. An unquestionable diagnosis can be made at histology of synovial and/or cutaneous nodules. Multicentric reticulohistiocytosis is considered an uncommon condition (nearly 100 cases in international literature to 1989); the authors believe it to be commoner though often misdiagnosed as a "variant of rheumatoid arthritis". PMID- 2236687 TI - [Pulmonary lymphangioleiomyomatosis. Radiologic aspects and the diagnostic role of computed tomography]. AB - Lymphangioleiomyomatosis (LAM) is an uncommon disease affecting women of reproductive capacity. It is characterized by non-neoplastic proliferation of smooth muscle in the lungs and, occasionally, in lymph nodes and in the thoracic duct. The patients present with dyspnea, chylous pleural effusion, pnx, and hemoptysis. The authors evaluated 4 patients with biopsy-proven LAM, by means of CT. In all cases, CT revealed small well-defined cystic air spaces with smooth and thin walls, scattered in the lungs. CT was very useful because it was more sensitive and specific than conventional radiography. The CT appearance of LAM distinctly differed from that of other diseases than can produce cystic air spaces in the lungs, such as UIP, eosinophilic granuloma, centri-acinar emphysema, and bronchiectasis. Our experience confirms the clinical usefulness of CT in diagnosing LAM. PMID- 2236688 TI - [Pericardial liquid layer as an occasional finding in internal echography. Normal patterns and pathologic limits]. AB - A small amount of fluid in the pericardial sac is often observed incidentally during upper abdomen US studies. In order to assess the normality range for this finding, 500 patients undergoing liver US were evaluated for the presence of pericardial fluid, the thickness of which was subsequently measured in positive cases. In a group of 20 patients with pericardial fluid thickness ranging 5-9 mm and in 6 cases with pericardial effusion greater than 10 mm, cardiologic evaluation was performed (clinical examination, ECG, echocardiography). Pericardial fluid was quite a common finding (20.8%) which had no clinical relevance when less than 10 mm. On the contrary, its clinical relevance was high when greater than 10 mm, and extending around the heart. PMID- 2236689 TI - [Correlation between the radiologic study of deglutition and the clinical picture in systemic sclerosis (scleroderma)]. AB - Fifty-one patients with systemic sclerosis (scleroderma) were studied by means of videofluoroscopy in order to evaluate the abnormalities in the oropharyngeal and esophageal phases of deglutition and to correlate the radiological patterns with the clinical features of the disease. Thirteen patients (25.5%) exhibited swallowing disorders such as oral leakage, retention, penetration, mild or moderate aspiration and abnormal upper esophageal sphincter behavior. These dysfunctions were more evident in patients with esophageal motility abnormalities. A normal radiological pattern in the esophagus was not associated with swallowing alterations. Remarkably, patients with oral-pharyngeal disorders had a higher incidence of lung diseases. Forty-five patients (88%) exhibited disorders of the esophageal phase of deglutition, such as mild or severe motility abnormalities or hiatal hernia, gastro-esophageal reflux, reflux esophagitis, and stricture. Radiological findings in the esophagus can be abnormal in the early stages of the disease. On the other hand, the radiological pattern of esophageal motility can be occasionally negative in advanced or extensive disease. This indicates a discrepancy between clinical symptoms and radiological picture of the esophagus. The radiological examination of the oral-pharyngeal and esophageal phases of deglutition is important in patients with scleroderma in order to evaluate visceral involvement, motility disorders, and risk of aspiration. Such radiological information can be useful in preventing esophagitis and pulmonary complications. PMID- 2236690 TI - [Ultrasonography in the diagnosis of chronic inflammatory intestinal disease]. AB - The accuracy of ultrasonography (US) in diagnosing active inflammatory bowel disease (IBD) is assessed on the basis of a randomized prospective study of 61 patients. Twenty-six of the patients were affected with Crohn's disease (CD) and 12 with ulcerative colitis, while the remaining 23 patients were control subjects with no specific chronic IBD. The US signs considered as significant for active CD and UC were: --visualization of a typical target image, that is a hyperechoic center corresponding to luminal bowel content, surrounded by a hypoechoic ring corresponding to loop walls; --at least 2 of the following: solid abdominal mass, distended loops, luminal narrowing, reduced peristalsis, stiff loops, and accumulation of fluid between the loops. US sensitivity and specificity for CD were 77% and 95.6%, respectively. As for UC, no significant results were obtained. In our experience, US is a reliable method for detecting alterations and, especially, complications typical of CD in its active phase. Considering the young age of the patients affected with CD and the number of exams they must undergo, US is considered as a useful tool in disease follow-up. PMID- 2236691 TI - [Tropical splenomegaly: echographic picture]. AB - Tropical splenomegaly is a pathologic condition due to multiple causes, endemic malaria being the major one. Twenty-eight black patients, 10 males and 18 females, residing in a tropical area, were investigated with US. The morphological features and major diameters of the spleen were studied and the splenic volumetric index (IVS) was calculated. Typical features were the presence of small intraparenchymal calcifications (46%) and the enlargement of splenic vessels, with US wall reinforcement (75%). No nodular lesions were detected, but increased frequency of organ lobulation was observed. A definite and uniform increase in splenic diameters was seen in all cases; IVS in particular was greater than the accepted confidence limit (21.5 +/- 6.5). This characteristic features should help the echographist to recognize this condition for they supply useful clinical information. PMID- 2236692 TI - [Invasive carcinoma of the cervix uteri (stage IB-IIB): evaluation using magnetic resonance]. AB - In patients with cervical carcinoma the selection of the optimal therapy depends on the precise preoperative assessment of the extent of disease. Currently, decisions regarding the management of these patients are made on the basis of clinical (FIGO) staging that has 50% mean error rate. To investigate the value of MR imaging in staging patients with invasive cervical cancer, we performed 25 MR examinations on 23 patients with histologic diagnosis of cervical cancer. All patients were clinically considered as having stage IB or IIB disease and underwent radical hysterectomy, providing specimens for pathologic correlation. The overall accuracy of MR imaging in staging cervical carcinoma (stage IB-IIB) was 78.1%. MR imaging seems to be the most reliable preoperative modality for staging invasive cervical cancer. PMID- 2236693 TI - [Pure and diluted contrast media in the visualization of the portal venous system using digital angiography]. AB - We report the results of intra-arterial digital subtraction angiography (DSA) in 100 patients with portal hypertension. The portal venous system was evaluated; all patients underwent angiography of the celiac and superior mesenteric arteries before surgery. Forty-four of them were also examined after Warren splenorenal shunts. Therefore, a total of 144 exams was evaluated. The authors always employed low-osmolality ionic and non-ionic contrast media (iodine concentration: 300-350 mg/ml). In 70 cases pure contrast medium was injected (20-25 ml); in the extant 74 cases it was diluted with an equal volume of saline solution (osmolality and iodine concentration reduced by 50%). Intra-arterial DSA always visualized portal venous system, collateral circulation, shunt location and postoperative changes. The major advantage of intra-arterial DSA is the smaller amount of contrast medium injected, so that local and systemic side effects are rare. According to our experience, it is best to dilute the contrast medium and inject the same amount as in conventional angiography, at the same rate. Other well-known advantages of intra-arterial DSA are quicker execution, less injury to arteries using smaller-caliber catheters, and low cost. The major disadvantage of intra-arterial DSA, as it appeared also in our study, is the field size of the intensifier, which in our case was limited to 6-9 inches. This is an insufficient coverage for the whole portal system to be studied, and some contrast medium injections become therefore necessary. An average of 3 injections were given to each patient. This problem reduces the advantage of less contrast medium per injection. At any rate, even though intra-arterial DSA exhibits this limitation, it can nevertheless yield important information in the pre- and postoperative evaluation of patients with portal hypertension. PMID- 2236694 TI - [Comparison of the results obtained using 99mTc HM-PAO tomoscintigraphy and computer tomography in ischemic lesions of the brain]. AB - Fifty patients suffering from cerebral ischemic attacks, transient or not, were studied with both 99mTc HM-PAO single photon emission computed tomography (SPECT) and computed tomography (CT). In 31 patients both SPECT and CT showed pathologic areas, the max diameters of which were measured on CT images and SPECT orbitomeatal reconstructed sections, and then compared. We observed that: only SPECT images are positive for pathologic conditions in transient ischemic attacks and in the very early phases of infarctions; in recent infarctions (less than 15 days earlier) both SPECT and CT scans are positive but SPECT lesion areas are greater than CT ones; pathologic areas, with clear-cut outlines, having the same dimensions on both CT and SPECT images, are supposed to result from old static infarctions. A persistent perilesional hypoactive area on SPECT images means, in our opinion, a hypoperfusional area liable to new vascular troubles; in which case, medical/surgical therapy seems necessary. PMID- 2236695 TI - [Simplified urographic technique using non-ionic contrast media]. AB - Urography is not to be performed following a standard procedure. However, some key-films can be defined which are to be routinely employed. If needed, additional radiographs can be performed. We tried to optimize the urographic technique combining low X-ray exposure and adequate diagnostic assessment with the injection of 17.5 gI of a non-ionic agent. Two groups of 50 patients each were investigated. In the former, the technique we currently employ in our Institute was used: plain film, 2 nephrotomograms (1'), full-length view (7'), kidney view with ureteral compression (15'), and full-length or bladder view (20'). In the latter group, a more simplified technique was used: plain film, 2 nephrotomograms (1'), kidney view (7'), and full-length view (15'). A compression device was positioned immediately before contrast medium injection and released immediately before the 15-minute exposure. Both urographic techniques allowed high scores to be reached (after the Kelsey Fry method), with no significant differences among the evaluated parameters. Thus, the technique employed on the second group is to be preferred, because it shortens examination time and reduces X-ray exposure. However, a simplified technique increases the radiologist's responsibility: it is thus essential for an experienced uroradiologist to accurately supervise the procedure and immediately decide what to do next. PMID- 2236696 TI - [Evaluation of the quality of screen-film radiographic systems: physical principles and methods of measurement]. AB - Comparative evaluation of radiographic film-screen systems presents several problems from both the theoretical and the experimental point of view. From the theoretical point of view the main difficulties are related to the choice of the parameters best suited to express the "overall quality" of a system. From the practical point of view the main problem is that to measure some basic quantities (resolution and noise) sophisticated and expensive instruments are required. This paper deals with both these problems. To express image quality we have assumed the signal-to-noise power ratio: this index depends in a explicit way on contrast, resolution and noise of the system. The dependence on sensitivity is implicit and was derived using literature data. From a knowledge of the dependence of image quality on sensitivity it is possible to develop an "overall quality" index which is considered to express the "technological level" of the system. This index can be used in the comparative evaluation of the different systems. In this work some basic physical quantities (characteristic curve, sensitivity) were evaluated using standard instruments. To measure spatial resolution and noise an inexpensive, PC-based, TV-digitizer system was developed. As an example, both image and overall quality indices were evaluated on three mammographic systems which are typical of the three different "phases" of the development of this technique. PMID- 2236697 TI - [Intra-arterial regional chemotherapy and intensive loco-regional radiotherapy in the treatment of locally advanced cancer of the breast]. AB - A multimodal treatment combining intra-arterial chemotherapy and intensive loco regional radiotherapy was administered to 55 patients with locally advanced breast cancer. Adjuvant polychemotherapy followed, and eventually endocrino therapy. Combined intra-arterial chemotherapy and intensive radiotherapy gave excellent results in both primary and lymph node lesions, with 90.9% and 92.2% complete/partial response rates. Three-year and 5-year actuarial survival rates were 69% and 59%, respectively. Patients showing better local responses to combined intra-arterial chemotherapy and intensive radiotherapy had longer survival and less frequent local recurrences. Combined intra-arterial chemotherapy and intensive loco-regional radiotherapy seems to be an effective modality for the treatment of locally advanced breast cancer. PMID- 2236698 TI - [Breast metastasis from melanoma. Description of a case]. PMID- 2236699 TI - [Mammographic aspects of juvenile papillomatosis: 4 case reports]. PMID- 2236701 TI - [Familial metaphyseal dysplasia (Pyle's disease) versus craniometaphyseal dysplasia. Presentation of a case]. PMID- 2236700 TI - [Intracystic papilloma of the breast. 3 case reports]. PMID- 2236702 TI - [Astragalocalcanean synostosis. Computer tomography diagnosis]. PMID- 2236703 TI - [Ultrasonic and computer tomography diagnosis of schwannoma of the tibial nerve. Description of a case]. PMID- 2236704 TI - [A case of arterio-venous fistula as a late complication of percutaneous puncture of the humeral artery in vertebral angiography: diagnosis using color Doppler]. PMID- 2236705 TI - [Cystic ganglioneuroblastoma of the adrenal glands in childhood: ultrasonic and CT aspects]. PMID- 2236706 TI - [Ruptured aneurysm of the renal artery. Computed tomographic diagnosis]. PMID- 2236707 TI - [Bilateral renal location: is it a double tumor or a contralateral metastasis?]. PMID- 2236709 TI - [Fundamentals and requirements of peripheral electric nerve stimulation. A contribution to the improvement of safety standards in regional anesthesia]. AB - The use of a nerve stimulator allows an injection cannula to be located without the cooperation of the patient. Regional anesthesia thus becomes safer because the basic condition "no paresthesia, no anesthesia" becomes irrelevant. In accordance with the basic electrophysiological conditions, a stimulator should have the following properties: (1) adjustable constant current at resistances of 0.5-10 kOhm; (2) monophasic square-wave initial impulse; (3) impulse duration selectable (0.1 ms + 1 ms, and exactly adjustable; (4) impulse amplitude (0-5 mA) exactly adjusted, unequivocal scale graduation or current indicator, in particular in the range of 0.05-1.0 mA; (5) impulse frequency 1-2 (-3) Hz; (6) alarm at high impedance and check on electrical circuit; (7) battery test (indication of battery voltage); (8) unequivocal assignment of load end; (9) high quality connecting cable and plug; and availability of (10) instructions for use with relevant parameters (tolerated variations, steady-state characteristic curves, etc.). PMID- 2236708 TI - [Role of transrectal ultrasonography in the diagnosis and follow-up of prostatic abscess. Description of a case]. PMID- 2236711 TI - [No effect of injection volume on sensory and motor blockade in isobaric spinal anesthesia]. AB - The authors were interested to find whether the course of sensory and motor blockade in isobaric spinal anesthesia was determined by the dose or the volume of the anesthetic agent. In a randomized double-blind study in 60 patients, each underwent isobaric spinal anesthesia with 17.5 mg bupivacaine. In three groups of 20 patients, this dose was administered as 3.5 mg bupivacaine 0.5%, 7 ml bupivacaine 0.25% or 10 ml bupivacaine 0.175%. The development, spread and regression of sensory block (anesthesia, analgesia) and motor block (Bromage scale, rectus abdominis muscle test) were determined. The clinical data recorded in the three groups were comparable. The rate of development, the maximal spread or intensity, and the regression of sensory and motor blockade did not differ in the three groups. The only difference was that the complete regression was shorter following 10 ml bupivacaine 0.175% (P less than 0.05). It is therefore concluded that the dose, and not the volume, determines the course of sensory and motor blockade of isobaric spinal anesthesia. PMID- 2236710 TI - [The effect of injection speed and needle gauge on the spread of sensory blockade in spinal anesthesia]. AB - Unanimity has not yet been reached on the influence of injection speed and needle size on the spread of sensory blockade in spinal anesthesia. While McClure et al. [6] proved that a change in injection speed had no effect on the spread of the blockade, Lanz et al. [4] showed in their investigation that increasing injection speed increases the spread of the blockade. The influence of needle size has hardly been investigated so far. Moore et al. [7] report that the needle size alone has no effect on the spread of the blockade. In this study the influence of injection speed and that of needle size on spread of sensory blockade were considered separately. MATERIALS AND METHODS. Spinal puncture was performed via the midline approach at the L3-4 interspace with the patient in a sitting position. Immediately after the induction of anesthesia the patients were placed in the supine position again. As local anesthetic 15 mg (3 ml) bupivacaine 0.5% with epinephrine 1:200000 was administered. The aim of the study was to find out how far injection speed and size of the spinal needle influenced the sensory spread in isobaric spinal anesthesia. The height of sensory blockade was assessed by means of the pin-prick method in the midline, and the onset of analgesia was determined as height of spread. The injection speeds for the local anesthetic solution were 0.25, 0.5 and 1 ml per second. The needle sizes were 22, 25, and 29 gauge. Each group consisted of 15 patients. RESULTS. It turned out that slow (0.25 ml/s) and the fast (1 ml s) injection was associated with a significantly higher level of analgesia than the medium one (0.5 ml/s). Cephalad spread was to T7 in the first two groups, while the medium injection speed only achieved a level of T9. The results are statistically significant (P less than 0.05). The comparison of different needle sizes (22, 25, and 29 gauge) used for spinal anesthesia showed a higher spread of the sensory blockade with increased diameter of the spinal needle given a constant injection speed. With the 22-gauge needles (n = 15) sensory blockade extended on average to T7, with 25-gauge needles (n = 15) to T9, and with 29-gauge needles (n = 15) to T10. It has to be mentioned, however, that with the 29-gauge needle the standard injection speed of 0.5 ml/s could not be achieved because of the small inner diameter. The differences between 22- and 25-gauge needles are statistically significant (P less than 0.05). DISCUSSION. No direct relation could be proved between the different injection speeds and the spread of the blockade. Our results are hardly comparable with those of other investigators, since other groups have used different local anesthetics or performed investigations in vitro. The use of large spinal needles is associated with spread of the spinal block to a significantly higher level than is achieved with thinner needles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2236712 TI - [The effect of volume and dosage of isobaric bupivacaine on the sensory spread of spinal anesthesia]. AB - There is some controversy about the relationship of volume, concentration and total dose of bupivacaine in the sensory spread of spinal anesthesia. In this study the effects of volume and dose were investigated. MATERIAL AND METHODS. In this study 120 patients undergoing lower extremity, inguinal or transurethral surgery were randomly divided into six groups. Bupivacaine 15 mg with the addition of epinephrine 1:200,000 was administered in 2 ml (0.75%), 3 ml (0.5%), 6 ml (0.25%) and 9 ml (0.166%) solutions. In addition 3 ml isobaric bupivacaine in doses of 7.5 mg (0.25%), 15 mg (0.5%) and 22.5 mg (0.75%). The spinal puncture was performed via the midline approach at the L3-4 interspace, with the patient in the sitting position. The injection speed was 0.5 ml per second. Immediately after the injection the patients were placed in the supine position. The spread of sensory blockade was assessed by means of the pin-prick method in the midline. Motor blockade was assessed on the Bromage scale 0-3. RESULTS. There were no statistically significant differences in motor blockade or cardiovascular changes. The maximum cephalad spread of analgesia (30 min) between the 15 mg groups with different volumes and concentration was: group I (9 ml): T7.7, group II (6 ml): T7.8, group III (3 ml): T8.5 and group IV (2 ml): T10.1. The differences between group IV 2 ml and the groups receiving 3, 6 and 9 ml were statistically significant (P less than 0.05). There were no statistically significant differences in maximum cephalad spread between the 7.5 mg (3 ml), 15 mg (3 ml) and the 22.5 mg (3 ml) groups. The regression after 180 min was significantly shorter in the 7.5 mg group than in the 15 mg and 22.5 mg groups (P less than 0.05). DISCUSSION. Earlier published results indicate that the dose of isobaric bupivacaine is more important in spinal anesthesia than the concentration or the volume of the solution. The comparison between 3 ml:6 ml and 3 ml:9 ml bupivacaine showed no statistically significant differences in cephalad spread. A volume-dependent increase in segmental spread was between the 2 ml (0.75%) and 3 ml (0.5%) bupivacaine. The same statistically significant differences were between the 2 ml and 6 ml groups and the 2 ml and 9 ml groups. No statistically significant difference in cephalad spread resulted from increasing the dose of bupivacaine from 7.5 mg to 22.5 mg. Earlier studies on the effects of changes in volume, concentration and dose of bupivacaine showed similar "jumps of blockade" between 2 ml and 3 ml injected volume. Assembling the results the relation between volume and total dose does not suggest a no linear dependence. The anatomic configuration of the spinal cord at the conus medullaris may affect the distribution of the solution. PMID- 2236713 TI - [The effect of patient positioning on the spread of sensory blockade in hyperbaric and isobaric spinal anesthesia using bupivacaine]. AB - Two prospective studies were performed to assess for how long after the subarachnoid injection of local anesthetics changes in position influence the cephalad spread of sensory blockade. Divergent accounts have been given by other groups. Besides the patient's position other factors may influence the cephalad spread of sensory blockade such as baricity of local anesthetics, speed of injection, dose, volume, barbotage and size of needle. Pashalidou found that after a supine position for 5 or 10 min, followed by Trendelenburg position for 5 or 10 min, there were significant differences in the increase of sensory blockade; the following two prospective studies were carried out with this in mind. METHODS AND MATERIAL. Study 1. Injection of the local anesthetics in sitting position, puncture at L3/4 interspace using a 25-gauge needle, speed of injection 3 ml/10 s, without barbotage. After injection the patients were supine for 30 min, then changing to the Trendelenburg position (n = 20) or the lithotomy position (n = 20), each for 20 min. The spread of blockade was tested by means of pin-pricks in the midline at 5-min intervals. Local anesthetics used were bupivacaine 0.5% with adrenaline (1:200,000) (n = 20) and bupivacaine 0.5% in 8% glucose (n = 20), 3 ml each. Study 2. Intrathecal injection was done as described above, but the speed of injection was 3 ml/6 s. Local anesthetics used were bupivacaine 0.5% with adrenalin (1:200,000) and bupivacaine 0.5% with adrenalin (1:200,000) in 5% glucose, 3 ml each. The patients were kept supine for either 15 or 20 min followed by 20 degrees Trendelenburg position for 10 min. RESULTS. Study 1. The mean spread of sensory blockade with isobaric bupivacaine was 16.95 segments (T6). After the 20 degrees Trendelenburg position the spread of blockade increased by 0.85 segments. After the lithotomy position there was no increase in sensory blockade. With hyperbaric bupivacaine the mean spread of sensory blockade after 30 min in the supine position was 17.3 segments (T5/6). After the Trendelenburg position there was no increase in sensory blockade. After the lithotomy position the sensory blockade spread by 0.4 more segments. This shows that there is no significant increase of cephalad spread of sensory blockade with either isobaric or hyperbaric bupivacaine. Study 2. With isobaric bupivacaine the mean spread of sensory blockade (n = 15) after 15 min in the supine position was 14.4 segments (T8/9). Following the Trendelenburg position the caphalad spread was increased by 0.93 segments (p less than 0.05). With hyperbaric bupivacaine the mean spread of sensory blockade (n = 15) was 16 segments (T7). Following the Trendelenburg position the spread was extended by 2.0 segments (p less than 0.05). After 20 min in the supine position following isobaric bupivacaine the mean spread of the sensory blockade (n = 15) was 15.4 segments (T7/8).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2236714 TI - [The effect of barbotage on the sensory spread in spinal anesthesia using isobaric and hyperbaric 0.5% bupivacaine]. AB - The effect of spinal anesthesia with barbotage versus without barbotage on the spread of analgesia was investigated. For comparison, hyper- and isobaric bupivacaine 0.5% with adrenaline 1:200,000 was used. MATERIAL AND METHODS. Barbotage was accomplished as follows: after lumbar puncture 0.5 ml CSF was aspirated into the local anesthetic solution, followed by reinjection of 1.0 ml of the solution. This process was repeated six times. Sixty patients who were scheduled for urological or lower limb surgery under spinal anesthesia were selected for this study. Patients were each arbitrarily assigned to one of four groups (isobaric and hyperbaric, without and with barbotage). RESULTS. There was no statistically significant difference in the maximum level of sensory analgesia. The mean maximum level of sensory analgesia reached T9 (group 1), T8 (group 2), T9 (group 3) and T8 (group 4). Time to highest dermatome was significantly shorter with barbotage (groups 1-4: 19.0 min, 13.0 min, 18.7 min, 12.3 min). Times for regression of analgesia to T12 (mean maximum duration) were 142 (+/- 54.9) min, 164 (+/- 29.7) min, 130 (+/- 40.4) min and 144 (+/- 36.2) min (groups 1-4). Motor block grade 3 (Bromage) was achieved in significantly shorter times with barbotage than without. The shortest onset time was recorded with isobaric bupivacaine. The onset time of a complete motor block was 12.5 (+/- 5.5) min in group 1, 6.1 (+/- 2.9) min in group 2, 15.8 (+/- 4.7) min in group 3, and 11.7 (+/- 5.1) min in group 4. CONCLUSIONS. The results showed no significant differences between the maximum segmental sensory levels or duration of anesthesia observed with isobaric and with hyperbaric bupivacaine (with and without barbotage). Sufficient analgesia was obtained with barbotage and without barbotage. Uncontrolled cephalad spread of spinal anesthesia was not observed. Barbotage has the advantage of shortening time for spread to highest dermatome and the time to onset of complete motor block. PMID- 2236715 TI - [The function of peripheral nerve stimulators in the implementation of nerve and plexus blocks]. AB - A selection of nine instruments supplied by eight different manufacturers for carrying out peripheral nerve stimulation were checked for their suitability, safety and ease of operation, and were compared and contrasted with reference to a spectrum of characteristics that appear desirable in theoretical and practical terms. Measurements at Ohm's resistance showed that in the clinically relevant range of impulse amplitudes (0.1-1.0 mA) the quality of adjustment of the instruments varied widely. The actual electrical impulse delivered by some of the instruments deviated so widely from the adjusted theoretical value that they must be regarded as unsuitable. The duration of the impulse corresponded to the manufacturer's specifications for only two instruments. Four instruments did not generate a monophasic square-wave signal despite assertions to the contrary in the instructions for use, and one instrument did generate such a signal although a "special biphasic asymmetrical" impulse is described by the manufacturer. Impulse-like overshooting at the beginning of the signal, oscillations into the positive range at the end of the signal and fall in current during the course of the signal were the form variants indicating technically inadequate design in the other instruments. Resistance to the square-wave current impulse engendered by the complex body resistance (impedance), a good approximation to the mathematical e-function to be expected, could be demonstrated for the rising signal flank, whereas the signal curve in the lower part of the descending flank was flatter than expected owing to polarization effects in the body tissue. The characteristic voltage and time values calculated for the signal curves are shown in tables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236716 TI - [In electric nerve stimulation can the distance from the nerves be inferred from the intensity of muscle contraction? Possible parameters and sources of error]. AB - Electrical nerve stimulation is a useful tool in regional anesthesia; it assists in locating the nerves. This investigation deals with electrical resistances at adhesive electrodes attached to the skin. The influence of external electrical resistance on the stimulating impulse is demonstrated. A new type of nerve stimulator is described; which integrates a measuring device that indicates the electrical impulse actually flowing in the patient. With this device, relationships between stimulating impulse, intensity of muscle contraction, and distance of the puncture cannula from the nerve can be assessed. MATERIALS AND METHODS. The electrical curve I = f (R) was determined using 3 different nerve stimulators (R = 1 - 15k omega). On each of five test persons, five adhesive electrodes were attached to the skin 10 cm apart. The resistance was assessed between these electrodes and a subcutaneously inserted puncture needle. The right and left brachial plexuses of the 5 subjects were punctured, using the axillary approach. A synchronized video camera simultaneously recorded the following values: (1) electrical impulse; (2) corresponding muscle contraction; and (3) the position of the puncture cannula. A scale ranging from 0-5 was applied to define the strength of the muscle contractions. RESULTS. The external resistance as measured under clinical conditions may limit the output impulse of nerve stimulators. In this case, the exerting impulse is lower than that indicated by the appliance. This error can only be identified using an impulse-measuring device. Nerve stimulators not equipped with a measuring device increase the risk of malpuncture, potentially resulting in nerve lesions. Skin resistance at adhesive electrodes varied from patient to patient within a range of 1.1 to 8.2 K omega. Preparing the skin appropriately (wiping with sandpaper) decreased the resistance by only 6% during the first 30 min. Within a distance of 50 cm to the puncture needle, the position of the adhesive electrode did not play a significant role. Axillary puncture of the brachial plexus resulted in the following values: (1) A stimulating impulse (cross-wave) of 1 mA and 1 ms exerted at a distance of 4 mm to the nerve induced a contraction of strength 3. (2) Reducing the impulse at this site by one-half (0.55 mA) resulted in just-visible contractions (strength 1). (3) Advancing the cannula at a stimulating impulse of 0.55 mA inside the neurovascular sheath again produced contractions of strength 3. (4) Performing the puncture with a blunt needle and tracing a distinct resistance, the impulse of 0.6 mA elicited contractions of strength 2. The needle tip was still outside the vascular nerve sheath. If this resistance was overcome and the needle tip lay inside the neurovascular sheath, the impulse could be reduced by one-half (0.32 mA) to produce contractions of strength 2. PMID- 2236717 TI - [A peridural catheter obstructed with glass particles--should a filter always be used in a test dose?]. PMID- 2236719 TI - Role of lymphatics in peritoneal dialysis. PMID- 2236718 TI - Acute renal failure due to falciparum malaria. AB - Seventy-two patients with severe falciparum malaria are described. Twenty-four (33.3%) were complicated by acute renal failure. Comparing patients with renal failure and those without, statistically significant differences occurred regarding presence of cerebral malaria (83% vs 46%), jaundice (92% vs 33%), and death (54% vs 17%). A significantly higher number of patients with renal failure were nonimmune visitors to malaria endemic regions. Renal failure was oliguric in 45% of cases. Dialysis was indicated in 38%, 29% died in early renal failure, and 33% recovered spontaneously. It is concluded that falciparum malaria is frequently complicated by cerebral malaria and renal failure. As nonimmune individuals are prone to develop serious complications, malaria prophylaxis and vigorous treatment of cases is mandatory. PMID- 2236720 TI - Lupus nephritis at the University Hospital of the West Indies, Kingston, Jamaica: a 10-year experience. AB - The case records of 75 patients who had systemic lupus erythematosus (SLE) and renal involvement on renal histology were reviewed. There were 70 females and 5 males, with a ratio of 14:1. The majority of the patients were in their second and third decades of life. SLE nephritis was distinctly uncommon in patients below 10 years of age and above 50 years of age. In nearly 80% of the patients, SLE nephritis was diagnosed within the year prior to presentation. The most common presenting clinical features were arthritis in 78% and a rash in 48%. The two most common renal features were proteinuria in 60% and renal failure in 55%. Of these patients, 20%, 12%, 48%, and 17% fell into Class II (mesangial GN), Class III (focal GN), Class IV (diffuse GN), and Class V (membranous GN), respectively, when the renal histological abnormalities were categorized according to the World Health Organization classification. The remaining 3% of patients had sclerosis and as a result were unclassifiable. The two major clinical manifestations in the Class IV patients were an acute nephritis syndrome in 83% and renal failure in 61%. The nephrotic syndrome was seen in 62% of Class V (membranous GN) cases. There was 100% survival in Classes II (mesangial GN) and V (membranous GN), and 62% percent in Classes III (focal GN) and IV (diffuse GN) combined. PMID- 2236721 TI - Recent developments in the pathogenesis of hemolytic uremic syndrome. PMID- 2236722 TI - The spectrum of acute renal failure in a developing country. PMID- 2236723 TI - Variations of glomerular properties and their effect on glomerular disease. AB - The possibility that inherited glomerular properties predispose individuals to certain glomerulopathies is an exciting new hypothesis. It opens new avenues to the investigation and treatment of patients which may be most easily applied in newly diagnosed diabetics and patients with multiple relapses of minimal change nephropathy. These treatments are unlikely to involve dangerous cytotoxic drugs which have been the fruit of years of investigation concentrated on the immune and inflammatory consequences of glomerular diseases. The differences between the two strains also cast doubt on the wisdom of extrapolating results obtained in the Munich Wistar rat to the rest of the animal kingdom. PMID- 2236724 TI - Cardiac conduction defects associated with aortic and mitral valve calcification in dialysis patients. AB - The prevalence of aortic valve and mitral valve or mitral annular calcification by echocardiography was studied in 66 dialysis patients and correlated with results of 24-h ambulatory and resting ECG data and 12-month survival. The well known association of mitral valve or mitral annular calcification with cardiac conduction defects was confirmed. Those patients with mitral valve or mitral annular calcification demonstrated a higher prevalence of first-degree atrioventricular block and bundle branch block. Despite advanced age and these conduction defects, those patients with mitral valvular calcification did not show decreased survival at 12 months. PMID- 2236725 TI - Intraocular pressures during high-flux hemodialysis. AB - The intraocular pressures of 16 patients with end stage renal failure treated with high-flux dialysis were measured before and during a high-flux dialysis treatment. The patients were selected so as not to have glaucoma or history of glaucoma. Intraocular pressures did not change significantly in any patients during or following a high-flux hemodialysis treatment. These data suggest that high-flux hemodialysis does not result in increases in intraocular pressure nor does it precipitate acute glaucoma in well-dialyzed patients undergoing intermittent in-center hemodialysis. PMID- 2236726 TI - Calcium channel blocker nisoldipine in chronic renal failure. AB - Patients with a stable progression of chronic renal failure with a creatinine clearance of 15-45 mL/min were randomly assigned to two groups of antihypertensive therapy: 1--nisoldipine as the only antihypertensive agent and 2 -antihypertensive drugs without calcium channel blockers and a placebo tablet instead of nisoldipine. The patients were already on a low-protein diet and some form of antihypertensive therapy but without calcium channel blockers. There were 18 patients in the placebo group and 20 patients in the nisoldipine group. The follow-up period averaged 23.7 +/- 10.6 (SD) months in the placebo group and 23 +/- 11.3 months in the nisoldipine group. The slopes of the reciprocal of serum creatinine were calculated for the period prior to and following our intervention. The number of patients whose slopes improved following intervention was 6/18 in the placebo group and 15/20 in the nisoldipine group (p less than .02). The patients whose slopes improved had a significant fall in systolic and diastolic BP, as well as in the MAP. Those whose slopes did not improve had a significant decrease in systolic BP, but no change in diastolic BP and no significant difference in the MAP. When all 38 patients are analyzed together, regardless of their grouping, the correlation between the difference percent in the slope, and the difference percent in the MAP, was significant. Furthermore, punch biopsies of the skin showed a markedly different calcium content in the two groups, which was significantly less in the nisoldipine-treated patients as compared with the patients not receiving calcium blockers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236727 TI - An epidemic outbreak of Serratia marcescens septicemia in a hemodialysis unit. PMID- 2236728 TI - The effect of successful renal transplantation on hormonal status of female recipients. AB - The pituitary, thyroid, and ovarian hormone levels were measured by enzyme and fluorescence polarization immunoassays in 18 women with successful renal transplants (recipients): 10 menstruating, mean age 34.7 years, mean time after transplantation (Tx) 112.00 months, mean SCr 130.60 mumol/L; and 8 menopausal, mean age 52.7 years, mean time after Tx 61.00 months, and mean SCr 119.00 mumol/L. Five women of the menstruating group conceived 7 times and gave birth to 4 healthy infants. The findings were compared to 30 age-matched healthy subjects (controls) and to 13 women under chronic hemodialysis (hemodialyzed patients): 2 menstruating, 24 and 36 years old, and 11 menopausal, mean age 59.4 years. Serum prolactin (PRL) showed a highly significant increase in hemodialyzed patients (p less than .0001) compared to controls. In recipients, PRL levels were significantly lower than in hemodialyzed patients, but higher than in controls (p less than .0001). LH and FSH were elevated in menstruating hemodialyzed patients (p less than .0001, p less than .02, respectively) and significantly high in menopausal hemodialyzed patients (p less than .02, p less than .01, respectively). In menstruating recipients, LH was also highly elevated (p less than .001), while FSH showed no significant difference from controls. In menopausal recipients the increase of LH was less prominent (p less than .02) but FSH was highly increased (p less than .001). T3, T4, and FTI were absolutely normal in recipients, while they were significantly lower than normal (p less than .0001) in hemodialyzed patients. Estradiol showed no significant difference in both groups of recipients, as well as in menopausal hemodialyzed patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236729 TI - Comparison of toxicity of radiocontrast agents to renal tubule cells in vitro. AB - We have previously reported that radiocontrast agents induce direct renal tubule cell toxicity in vitro. The observed toxic effects were markedly potentiated by concomitant hypoxia. In addition, we have reported that the ionic radiocontrast agent diatrizoic acid is more toxic than the nonionic radiocontrast agent iopamidol in this system. Using suspensions enriched in rabbit renal proximal tubule segments, we compared the direct toxicities of the ionic dimeric ioxaglic acid to the nonionic monomeric compound iopamidol. Toxicity was assessed by comparing tubule potassium and calcium content, ATP levels, and respiratory rates after exposure to clinically achievable concentrations of radiocontrast agents. Ioxaglate (25 mM) produced significant declines in tubule cation content and respiratory rate with 30 min of hypoxia followed by 60 min of reoxygenation compared to molar-equivalent concentrations of iopamidol under similar conditions. Meglumine, a cationic compound frequently present in ionic contrast agent solutions, and ioxaglate tubule toxicity was additive. Iopamidol and ioxaglate exhibited similar tubule cell toxicity when comparison was based on iodine content. These experimental results suggest that the intrinsic nephrotoxic potential of ioxaglic acid is greater than that of iopamidol on a molar basis, but that the nephrotoxic potential of the two radiocontrast agents is similar when comparison is based upon iodine content. PMID- 2236730 TI - Differential susceptibility to gentamicin toxicity within the proximal convoluted tubule. AB - The proximal convoluted tubule (PCT) is the major target for injury in gentamicin nephrotoxicity but the necrosis is often patchy and focal. The PCT is structurally, functionally, and metabolically heterogeneous, and the possibility of differential vulnerability to gentamicin-induced necrosis based on this heterogeneity has not been examined. A quantitative analysis comparing the extent of necrosis in the initial portion of the PCT (S1) to that in the more distal PCT (S2) and comparing necrosis in the PCT of superficial nephrons to that in juxtamedullary nephrons was done in rats after eight daily intraperitoneal doses of 100 mg gentamicin/kg rat weight. The results indicate that the PCT of superficial nephrons are more susceptible to necrosis than the PCT of juxtamedullary nephrons and that the initial S1 segment even in the superficial nephrons is remarkably resistant to injury. These findings suggest that some aspects of the functional or metabolic heterogeneity within the PCT may be related to either differential rates of uptake of the drug or to differences in intrinsic susceptibility to its toxic effects. PMID- 2236731 TI - The effect of calcium channel blockers on the cyclosporine dose requirement in renal transplant recipients. AB - Thirteen patients found to be hypertensive following renal transplantation were treated with either a calcium channel blocker or other antihypertensive therapy for control of blood pressure. Immunosuppression was either with cyclosporine and prednisone alone or with cyclosporine, azathioprine, and prednisone. Patients had weekly or biweekly cyclosporine whole-blood levels measured by radioimmunoassay drawn approximately 12 h after their last dose. Patients treated with cyclosporine and prednisone alone had their cyclosporine dosage adjusted to maintain their cyclosporine level between 400 and 900 ng/mL between 1 and 6 months following transplantation. Patients treated with cyclosporine, azathioprine, and prednisone had their cyclosporine level adjusted to be between 100 and 400 ng/mL during this same time period. Cyclosporine levels were significantly higher in verapamil-treated patients and significantly lower in nifedipine-treated patients as compared to controls. The dose of cyclosporine administered was significantly lower in the verapamil-treated patients and higher in the nifedipine-treated patients than controls. Normalizing the whole-blood cyclosporine level for the dose of cyclosporine, and verapamil-treated patients had a significantly greater, and the nifedipine-treated patients a significantly lower value than control patients. These data suggest the verapamil treatment results in significantly higher levels of cyclosporine whereas nifedipine therapy may actually result in lower cyclosporine levels for a given dose of cyclosporine than seen in patients not exposed to these drugs. PMID- 2236732 TI - Folate nephropathy occurring during cytotoxic chemotherapy with high-dose folinic acid and 5-fluorouracil. AB - High-dose folinic acid with 5-fluorouracil (5-FU) is a novel combination chemotherapy used in the treatment of metastatic gastrointestinal cancer. One of the mechanisms of action of 5-FU is its conversion into fluorodeoxyuridylate (FdUMP), which inhibits thymidilate synthetase (TS). The rate of inhibition of TS is augmented by increasing concentrations of folinic acid. On the other hand, it is well known that treatment of animals with high doses of folinic acid results in acute renal failure due to tubular obstruction. In order to find out whether there are similar findings in the clinical setting, we investigated 8 patients (pts.) with metastatic gastrointestinal cancer who were treated with this chemotherapy. We used the following parameters: 1. excretion of four urinary enzymes (LDH, LAP, GGT, NAG); 2. creatinine clearance on days 1 and 5. Therapy consisted of folinic acid 200 mg/m2 i.v. on days 1-5 and 5-fluorouracil 400 mg/m2 on days 1-5. Each treatment cycle was repeated on day 28. We found a constant decrease in the excretion of all 4 enzymes from normal to subnormal values which was statistically significant (p less than .05) during the two treatment cycles. Creatinine clearance decreased about 50% in three patients from normal initial values. In conclusion, during therapy with high-dose folinic acid and 5 fluorouracil we found signs of tubular damage which are similar to those found in folate nephropathy. PMID- 2236733 TI - Hyperlactatemia and increasing metabolic acidosis in hepatorenal failure treated by hemofiltration. AB - We report a case of increasing hyperlactatemia in the course of repeated treatment by machine hemofiltration (MHF) using a lactate-buffered replacement solution. The hyperlactatemia was associated with a reduction in mean arterial pressure, and in the majority of treatments a metabolic acidosis developed. Hyperlactatemia due to exogenous lactate may not be as benign as previously discussed. PMID- 2236734 TI - [Dye penetration of 3 temporary ready-to-use cements]. AB - Dye penetration following obturation of standardized access cavities with three different ready to use temporary cements was compared (Cavit G, Dentorit and Ciprospad). Leakage and dye penetration of the materials were simultaneously evaluated. Ciprospad appears to be the most adapted material. PMID- 2236735 TI - [Experimental study of the effect of a photopolymerizable glass ionomer cavity liner on pulp pressure and temperature]. AB - The biocompatibility of a light curing glass ionomer cement was studied for its pulpal effect when used as a capping agent in a dentin cavity. Pulpal pressure and temperature were recorded in 14 dog canines after placement of the glass ionomer cement. No increase was observed in 12 specimens on 14 samples. These results indicate that no pulpal effect can be demonstrated when using Vitrabond as a dentin capping agent. PMID- 2236736 TI - [Efficiency factors in endodontic instruments. Study of linear movement]. AB - This study of the efficiency of endodontic tools in a linear motion values different parameters. The cross section seems to be the most important factor. The triangular section instruments are more efficient than the square section ones, but are more easily worn. The helical angle, the outline and the diameter have no influence on the efficiency. PMID- 2236737 TI - [Treatment of a double periapical abscess]. PMID- 2236738 TI - [Titularization. Repeat of a treatment of left first mandibular molar]. PMID- 2236739 TI - [Titularisation]. PMID- 2236740 TI - [Daily practice and pulp diseases]. AB - Constructive or destructive processes of pulp tissue depend on many factors: anatomic topography, particular physiology, or intensity and duration of infectious, mechanical and chemical aggression. Also irritation of the pulpo dentinal complex induce histologic and physiologic changes. The positive diagnosis of hyperemia, acute or chronic pulpitis, pulpal necrosis and acute or chronic apical abscess is performed by clinical investigations which allow a differential diagnosis with other dental or extra-dental diseases. These multiple steps lead to an adapted and appropriate treatment. PMID- 2236741 TI - [Occlusion and complete dentures]. PMID- 2236742 TI - Lead in the environment: coming to grips with advocacy versus scientific integrity in risk assessment. PMID- 2236744 TI - Dermal uptake of organic chemicals from a soil matrix. AB - Uptake of chemicals from soil on human skin is considered. Based on a review of literature on the structure of human skin, the processes by which chemicals pass through this boundary, and experiments that reveal the rate and magnitude of this transport process; a two-layer model is presented for estimating how chemical uptake through the stratum corneum depends on chemical properties, skin properties, soil properties and exposure conditions. The model is applied to two limiting scenarios--(1) continuous deposition and removal of soil on the skin surface and (2) a one-time deposition of soil onto the skin surface. The fraction of soil-bound chemical that passes through the stratum corneum is dependent on the skin-soil layer thickness; the dimensionless Henry's law constant, Kh and the octanol-water partition coefficient, Kow of the soil-bound chemical. The nature of this dependence is discussed. PMID- 2236743 TI - Effects of the Chernobyl accident on public perceptions of nuclear plant accident risks. AB - Assessments of public perceptions of the characteristics of a nuclear power plant accident and affective responses to its likelihood were conducted 5 months before and 1 month after the Chernobyl accident. Analyses of data from 69 residents of southwestern Washington showed significant test-retest correlations for only 10 of 18 variables--accident likelihood, three measures of impact characteristics, three measures of affective reactions, and hazard knowledge by governmental sources. Of these variables, only two had significant changes in mean ratings; frequency of thought and frequency of discussion about a nearby nuclear power plant both increased. While there were significant changes only for two personal consequences (expectations of cancer and genetic effects), both of these decreased. The results of this study indicate that more attention should be given to assessing the stability of risk perceptions over time. Moreover, the data demonstrate that experience with a major accident can actually decrease rather than increase perceptions of threat. PMID- 2236745 TI - Associations between morbidity and alternative measures of particulate matter. AB - This paper explores the association between acute respiratory morbidity and different measures of exposure to airborne particulate matter, including sulfates, total suspended particulates, and fine and inhalable particulates. Regression analysis was used to test for the impacts of these alternative measures of particulate matter on respiratory morbidity using the 1979-1981 annual Health Interview Surveys and EPA's Inhalable Particle Monitoring Network. The general results indicate that, of the surrogate measures for particulate matter, sulfates appear to have the greatest association with morbidity. To the extent that sulfuric acid aerosols are correlated with airborne sulfates, the results suggest that respiratory impairment sufficient to lead to days of reduced activity may be related to the existence of acidity in the air. These findings are consistent with the results of ecological studies reporting an association between mortality and exposures to fine particles and sulfates. PMID- 2236746 TI - Comparison of the cancer risk of methylene chloride predicted from animal bioassay data with the epidemiologic evidence. AB - Methylene chloride has been shown to be a lung and liver carcinogen in the mouse; yet, the current epidemiologic data show no adverse health effects associated with chronic exposure to this compound. Hearne et al. have compared the results of a large mortality study on occupational exposure to methylene chloride to the human risk predictions based on the rodent bioassay to point out the inconsistency between the animal toxicologic and human epidemiologic data. The maximum number of lung and liver cancers predicted due to methylene chloride exposure based on the rodent bioassay data was 24 compared to 14 deaths from these cancers actually observed in the Hearne et al. epidemiology study. We assess the minimum risk detectable by the human study in order to calculate the upperbound potency of methylene chloride and compare it to the potency derived from the bioassay data. Results from the epidemiology study imply an upperbound potency of 1.5 x 10(-2) per ppm, compared to 1.4 x 10(-2) per ppm calculated using the most conservative analysis of the animal data. We conclude that the negative epidemiology study of Hearne et al. is not sufficiently powerful to show that the risk is inconsistent with the human risk estimated by modeling the rodent bioassay data. Specifically, the doses to which the workers were exposed, the population studied, and the latency period were not adequate to determine that the risks are outside the bounds of the risk estimates predicted by low-dose modeling of the animal data. PMID- 2236747 TI - Interpretation of airborne asbestos measurements. AB - Transmission electron microscopy (TEM) is the preferred method of measuring airborne asbestos in buildings, but TEM measurements cannot be used directly in the existing equations relating risk to exposure because the equations are based on measurements made with a different technique--phase contrast microscopy (PCM). Comparison between measurements made by different methods is not simple because the methods differ in the size of particles they can detect, and the relationship between exposure and disease is thought to depend on, among other things, asbestos fiber size. Previous suggestions for converting TEM measurements to PCM equivalents lack generality because they fail to take into account the size distribution of the asbestos particles and the expectation that fiber-size distributions in current nonoccupational environments could differ from the workplaces of the past on which the risk equations are based. A mathematical model is presented for investigating the conversion of airborne asbestos measurements made by one method to an equivalent measurement made by another method. "Equivalent" means having the same potential to cause disease. The model clarifies the issues of concern and suggests approaches for obtaining meaningful conversion factors that will allow TEM measurements to be used in PCM-based risk equations. PMID- 2236748 TI - Uncertainties in pharmacokinetic modeling for perchloroethylene. I. Comparison of model structure, parameters, and predictions for low-dose metabolism rates for models derived by different authors. AB - In recent years physiologically based pharmacokinetic models have come to play an increasingly important role in risk assessment for carcinogens. The hope is that they can help open the black box between external exposure and carcinogenic effects to experimental observations, and improve both high-dose to low-dose and interspecies projections of risk. However, to date, there have been only relatively preliminary efforts to assess the uncertainties in current modeling results. In this paper we compare the physiologically based pharmacokinetic models (and model predictions of risk-related overall metabolism) that have been produced by seven different sets of authors for perchloroethylene (tetrachloroethylene). The most striking conclusion from the data is that most of the differences in risk-related model predictions are attributable to the choice of the data sets used for calibrating the metabolic parameters. Second, it is clear that the bottom-line differences among the model predictions are appreciable. Overall, the ratios of low-dose human to bioassay rodent metabolism spanned a 30-fold range for the six available human/rat comparisons, and the seven predicted ratios of low-dose human to bioassay mouse metabolism spanned a 13-fold range. (The greater range for the rat/human comparison is attributable to a structural assumption by one author group of competing linear and saturable pathways, and their conclusion that the dangerous saturable pathway constitutes a minor fraction of metabolism in rats.) It is clear that there are a number of opportunities for modelers to make different choices of model structure, interpretive assumptions, and calibrating data in the process of constructing pharmacokinetic models for use in estimating "delivered" or "biologically effective" dose for carcinogenesis risk assessments. We believe that in presenting the results of such modeling studies, it is important for researchers to explore the results of alternative, reasonably likely approaches for interpreting the available data--and either show that any conclusions they make are relatively insensitive to particular interpretive choices, or to acknowledge the differences in conclusions that would result from plausible alternative views of the world. PMID- 2236749 TI - Mite control: is it worthwhile? PMID- 2236750 TI - Interactions between macrophages and granulocytes in allergic asthma. PMID- 2236751 TI - Late asthmatic responses. PMID- 2236752 TI - Tuberculosis screening and prevention in new immigrants 1983-88. AB - Although only 11 cases of active tuberculosis in new immigrants were found, 29.9% of those aged under 30 were tuberculin negative on entry and were given BCG vaccination. In addition 12.8% of children aged under 16 were strongly tuberculin positive and were given chemoprophylaxis. The defects of the official Port of Arrival system for reporting new immigrants are discussed. Entry screening of new immigrants allows worthwhile preventive action, BCG vaccination or chemoprophylaxis, in a substantial proportion of those screened. PMID- 2236753 TI - Skin reactivity to atypical mycobacteria in cystic fibrosis. AB - Atypical mycobacterial disease has been described in a small number of patients with cystic fibrosis. Apart from one uncontrolled study, there is little information regarding atypical mycobacterial skin reactivity in this group of patients. We evaluated delayed cutaneous hypersensitivity to purified extracts of Mycobacterium avium, Mycobacterium intracellular, Mycobacterium kansasii and Mycobacterium bovis in 23 healthy controls and 43 adult and adolescent patients with cystic fibrosis. Fifteen of the cystic fibrosis group were receiving regular corticosteroids. Additionally, direct smear examination and Lowenstein Jensen culture were performed on sputum from the cystic fibrosis group. The prevalence of positive skin reactions was similar in the group with cystic fibrosis (30%) and in the control group (57%). Subgroup analysis showed that those cystic fibrosis patients receiving corticosteroids had a markedly lower prevalence of positive reactions (7%) compared to controls (P less than 0.01). When this subgroup was excluded from analysis, the prevalence of positive skin reactions among patients with cystic fibrosis was 43%. In the prospective sputum bacteriology study, one of the 43 cases grew Mycobacterium avium-intracellulare and had clinical and radiological evidence of this disease. Of note, this patient showed positive skin tests to all four mycobacterial species tested. Our data show no difference in the prevalence rate of positive skin reactions to atypical mycobacterial antigens between a control population and an adult cystic fibrosis population. In addition, the predictive value of skin testing is low in cystic fibrosis due to the high prevalence of cross-reactivity between different mycobacterial species and the high prevalence of anergy among those patients with advanced disease receiving treatment with corticosteroids. PMID- 2236754 TI - Survey of student nurses' smoking habits in a London teaching hospital. AB - As a preliminary to a 3-year intervention project to reduce smoking levels and prevent smoking commencement among student nurses, a survey of smoking habits among all 368 student nurses at The Royal Free Hospital was conducted in the Autumn of 1988. Absence rates of smokers and those who had never smoked were also studied. The response rate was high (95%) and the survey showed a high percentage (43%) of smokers among the student nurses. There was a higher proportion of smokers among those who did not respond to the first mailing of the questionnaire. The absence rate among smokers was almost twice that of the nonsmokers (P less than 0.005) and the number of days absent was related to the number of cigarettes smoked (P less than 0.05). Sixty-two per cent of nurses who smoked before they started their training (n = 125) said they had increased their smoking since commencing training and 39 (11%) nurses started smoking after starting nurse training. 'Stress', greater opportunity to smoke and peer influence were given as reasons for increased smoking and smoking commencement during nurse training. PMID- 2236755 TI - Passive smoking in cystic fibrosis. AB - The families of 32 children with cystic fibrosis (CF) were interviewed about both their tobacco consumption and their childrens physical activities. Hospital records informed about treatment frequency, lung function and clinical score. Cystic fibrosis families smoked far more than the Swedish average and the passive smokers among our patients seemed to fare less well in all parameters. The children of smoking mothers required significantly longer periods of intravenous antibiotic treatment (P greater than 0.05). Frequent physical exercise seemed to compensate for the potential harmful effects of passive smoking and children with high physical activity living in families who smoked needed significantly less frequent antibiotic treatment than the inactive children (P greater than 0.02). Although this series is small, the results indicate that a smoke-free environment may be important for CF patients. General information is insufficient and extensive psychological support to the families is probably necessary. PMID- 2236756 TI - Prophylaxis of exercise-induced asthma with inhaled formoterol, a long-acting beta 2-adrenergic agonist. AB - The prophylaxis of exercise-induced asthma with inhaled formoterol (12 micrograms) was compared with inhaled salbutamol (200 micrograms) and placebo in 12 patients with atopic asthma. Both drugs produced equal bronchodilation 2 and 4 h after administration. Both drugs protected equally against exercise-induced bronchoconstriction 2 h after administration; at 4 h, formoterol gave undiminished protection from that seen at 2 h while salbutamol was no more effective than placebo. PMID- 2236757 TI - Experience with fibreoptic bronchoscopy in the diagnosis of pulmonary shadows in renal transplant recipients over a 12-year period. AB - Despite improvements in immunosuppressive therapy, pulmonary infections remain an important cause of morbidity and mortality in renal transplant recipients. Over a 12-year period (1 January 1977 to 31 December 1988) we prospectively assessed the value of fibreoptic bronchoscopy in diagnosing radiographic pulmonary shadows in this group of patients. Forty-eight bronchoscopies were performed on 46 patients. A definitive diagnosis was established in 28/48 (58%) procedures (and was partially definitive for one of two organisms ultimately identified in another). The procedure failed in 19/48 (40%), although in 15 of these, the radiographic shadows resolved on antibiotics (9) or spontaneously (3) or autopsy revealed acute pneumonia (3). In four instances a specific diagnosis was made by alternative means. Clinically useful information which led to changes in management was obtained in 17/48 (35%) procedures and bronchoscopy was thought to have favourably influenced survival in 16/48 (33%). Fibreoptic bronchoscopy is in our experience a safe (only one pneumothorax and no significant haemorrhage) and useful technique in evaluating pulmonary shadows in renal transplant recipients. PMID- 2236758 TI - Culture and comparison of human bronchial and nasal epithelial cells in vitro. AB - Human nasal and bronchial epithelial cells were cultured in vitro and compared morphologically and functionally. Morphologic assessment by both light and electron microscope and indirect immunoperoxidase staining techniques confirmed the identity of the two cell types as being epithelial. Light microscopy of confluent cultures revealed tightly packed cell monolayers, whilst electron microscopy showed that cells were linked by tight junctions. Estimation of cell size by planimetry found these cells to have a mean width of 10.6 +/- 1.1 microns for nasal cells and a mean width of 10.2 +/- 1.0 microns for bronchial cells. A high proportion of both the nasal and the bronchial cells exhibited features of the mature ciliated cell types, and constituted between 50 and 76% of the total cells at the earlier stages of culture although this decreased to between 16 and 23% of the total by 4 weeks in culture. The ciliary beat frequencies of the nasal and bronchial cells were found to be similar at 10.8 +/- 0.7 Hz and 11.8 +/- 2.3 Hz, respectively. The cilial beat on adjacent cells was synchronous, suggesting the presence of intercellular communication between the neighbouring cells. These studies demonstrated that there was little difference between the cultured nasal and bronchial epithelial cells with respect to either their morphology or ciliary activity. PMID- 2236759 TI - Antibacterial and mutagenic activity of inhaled bronchodilators on the respiratory pathogen Haemophilus influenzae. AB - The U.K. prevalence of non-beta-lactamase-mediated resistance to ampicillin among Haemophilus influenzae reached 4% in 1986. The majority (70%) of isolates of this type come from sputa of patients with chronic obstructive airways disease. This study investigated whether bronchodilator drugs delivered directly to the respiratory tract have any antibacterial activity and/or play a role in promoting selection of organisms with this type of resistance. Antibacterial activity was detected in two out of six pharmaceutical preparations for nebulization examination but was entirely attributable to the preservative (benzalkonium chloride) in them. Exposure of ampicillin-susceptible H. influenzae (minimum inhibitory concentration 0.25 mg l-1) to concentrations of salbutamol, fenoterol and beclomethasone theoretically attainable in vivo resulted, after 48 h, in isolation of colonies with reduced susceptibility to ampicillin (minimum inhibitory concentration 1-4 mg l-1) but reversion to beta-lactam susceptibility occurred following serial subculture on chocolate agar. Organisms with stable reduced susceptibility to ampicillin were obtained when exposure to one of these three bronchodilators in broth was followed by serial subculture on agar containing the same preparations at equivalent concentrations and when the period of exposure to salbutamol at 100 mg l-1 in broth was extended to 5 days. The occurrence of these phenomena in vivo might be contributing to failures in treatment of exacerbations with ampicillin and to an increasing prevalence of beta-lactamase-negative, ampicillin-resistant H. influenzae. PMID- 2236760 TI - Factors influencing the compliance of patients using oxygen concentrators for long-term home oxygen therapy. AB - A previous study in the Liverpool district on patients receiving long term oxygen treatment using a domiciliary oxygen concentrator showed that only 55% were both using oxygen therapy correctly and had stopped smoking. To try and identify which factors influence patient behaviour, all 55 patients in this district receiving long-term oxygen therapy for hypoxaemic chronic airflow limitation were studied. We found that those with more symptoms were more likely to comply with this therapy. The prescription of a concentrator on the advice of a hospital physician did not improve on the compliance rates attained in those patients assessed by the general practitioner alone. PMID- 2236761 TI - Estimation of pulmonary artery pressure by Doppler echocardiography in normal subjects made hypoxic. PMID- 2236762 TI - Wegener's granulomatosis presenting as pulmonary metastases: value of antineutrophil cytoplasmic antibodies in diagnosis. PMID- 2236763 TI - Relapsing polychondritis presenting with bronchorrhoea. PMID- 2236764 TI - [Tuberculosis and AIDS. The situation in Spain. The outlook]. PMID- 2236765 TI - [Spontaneous bacterial peritonitis in the cirrhotic patient. A study by discriminant analysis]. AB - Infection of peritoneal fluid in cirrhotic patients requires an early diagnosis and treatment. Different parameters have been used for the diagnosis of this complication, however, the statistical study has not used multivariable analysis techniques. We have therefore designed this work performing a discriminating analysis in order to find the best variable combination. Twenty-six cirrhotic patients who were consecutively admitted to our hospital have been studied. Total adn polymorphonuclear leukocytes, glucose, LDH, and lactic acid were determined in peritoneal fluid. Eighteen peritoneal fluids were classified as non infected and the rest as infected. The criteria obtained from the discriminating function which combines total leukocytes, LDH, and glucose has been chosen as optimal. The utility of discriminating analysis is discussed and we conclude with the need to verify in a later study the value of the calculated function. PMID- 2236766 TI - [A clinical and biological study of 33 cases of polycythemia vera]. AB - The clinical, analytical, evolutive and therapeutic aspects of 33 cases of polycythemia vera which were diagnosed according to the Polycythemia Vera Study Group criteria, are described. Mean age was 65 years with a slight predominance of females (54.5%). Hemorrhagic manifestations were the most frequent (67%) with a great number of patients with digestive manifestations consisting of GI hemorrhage, abdominal pain, portal or suprahepatic veins thrombosis. Splenomegaly was the most frequently found sign upon examination (73%). The mean hemoglobin leukocyte, and platelet levels were 18 g/dl, 16,000 mm3 and 738,000 mm3 respectively. It is note worthy the value of the erythropoietin for the differential diagnosis of secondary erythrocytosis as well as the value of the bone marrow histologic study which should be included in the diagnostic criteria of the disease. The evolution of the process is favorably altered by bleedings and chemotherapeutic cytoreduction which are often performed simultaneously. PMID- 2236767 TI - [Differences by sex in the presentation and follow-up in the first year of acute myocardial infarct]. AB - Three-hundred and nine patients, 242 males and 67 females diagnosed of myocardial infarction were studied during the acute phase and followed for a year to evaluate any differences. The corrected incidence was greater amongst males, 11.1 vs 3.6/10,000 inhabitants. The presenting age was significantly lower in males below 50 and greater in women above 70. Hypertension, hypercholesterolemia and sedentariness were more prevalent amongst women; smoking was more prevalent amongst males. Infarction presentation was typical in both sexes being significant a 5 hour delay in arriving to the hospital in female patients. On hospital admission Killip III-IV was significantly more frequent amongst women (17% vs 4.6%). Hospital mortality although it was higher in women this was not statistically significant (19.4% vs 14.4%). During follow up there was a better control of risk factors in the male patients. Heart failure and mortality were greater amongst women during the first three months (p less than 0.001). Mortality differences continued being statistically significant during the following three months. From the sixth month to the first year, mortality rates were similar. The study suggests that infarction prognosis is worse in females. PMID- 2236768 TI - [The reflex sympathetic dystrophy syndrome associated with breast cancer]. AB - Reflex sympathetic dystrophy syndrome (RSDS) is a rare entity of unknown etiopathogenesis, associated to different precipitating factors such as malignant tumors of several localizations. A new clinical variety has been recently described which has been denominated palmar fasciitis and polyarthritis syndrome. We present here two patients with RSDS associated to breast cancer: one case presenting fasciitis and polyarthritis and another case also associated to polymyalgia rheumatica. We emphasize the importance of reducing the tumor mass in the treatment of this syndrome, as well as including it in the gammagraphic differential diagnosis of bone metastasis. PMID- 2236769 TI - [The recurrence of a gynecological neoplasm as a solitary thyroid nodule]. AB - We present a case of a patient who sought medical assistance because of a single thyroid nodule and had a history of cervix carcinoma and hysterectomy three years earlier not having had any signs of progression of that disease since. The aspiration puncture of the thyroid nodule revealed atypical squamous cells suggestive of metastasis of the gynecological neoplasia. The rareness of the clinical presentation of the thyroid metastasis as well as of the involvement of this gland in the dissemination of cervix neoplasia are discussed, noting on the possible role of radiotherapy on the variation of the progression patterns of the disease. Similarly, the usefulness of cytology obtained by aspirative puncture with a thin needle, in the diagnosis of thyroid nodule is highlighted. PMID- 2236770 TI - [The human immunodeficiency virus type 2 (HIV-2)]. PMID- 2236771 TI - [The nutritional quality of the fat intake of the Spanish population]. AB - The present study originated because of the importance and current interest in fat intake and its relationship with cardiovascular diseases. The quality and quantity of fat intake is studied in the Spanish population as a whole, as well as in each of the Autonomic Communities. The quality of the ingested fat is analyzed considering the intake of saturated, monounsaturated, and polyunsaturated fatty acids using different index such as: polyunsaturated/saturated ratio (P/S), Keys, Anderson and Grande's index, and vegetable fat + fish fat/animal fat--fish fat ratio. The differences found according to the geographical localization of the Autonomic Community were studied, finding the influence of what is known as the "Mediterranean diet". PMID- 2236772 TI - [The characteristics of the opportunistic infections associated with AIDS: tuberculosis and toxoplasmosis]. PMID- 2236774 TI - [Is discontinuous digitalis therapy efficacious?]. PMID- 2236773 TI - [Abdominal pain and a palpable mass with previous abdominal surgery]. PMID- 2236775 TI - [Disseminated cryptococcosis as the first manifestation of the acquired immunodeficiency syndrome]. PMID- 2236777 TI - [Septic arthritis due to Haemophilus influenzae in adults]. PMID- 2236776 TI - [Hyperthyroidism, pregnancy and the panic attack]. PMID- 2236778 TI - [Intramuscular buprenorphine in the symptomatic treatment of renal colic]. PMID- 2236779 TI - [Pseudomonas and not Pseudomona, nothing to do with plural]. PMID- 2236780 TI - [Adenocarcinoma of the ovary in the ovarian remnant syndrome]. PMID- 2236781 TI - [Prognostic factors for success in catheter ablation of the right Kent bundle: report of 27 patients]. AB - In 27 patients with atrial fibrillation and/or reciprocating tachycardia, ablation of right-sided Kent bundles (23 in the right posterior paraseptal region and four of the right free wall) was performed. The anterograde refractory period of the accessory pathways was 253 +/- 70 msec and the shortest R-R interval during atrial fibrillation 211 +/- 47 msec. Cumulative energies of 589 +/- 396 J per patient were used, with 3 +/- 2 shocks and 195 +/- 312 J per shock. Accessory pathway ablation was effective in 16/27 patients (59%) during an 11 +/- 8 months of follow-up (in 15/16 pre-excitation disappeared; in nine of them the anterograde and retrograde conductions were abolished and in the other six the anterograde and retrograde conductions were severely altered; ablation was partially ineffective in 1/16 patients who remained asymptomatic on medical treatment and without inducible reciprocal rhythm). Ablation was ineffective in 11/27 patients. Three hours after ablation a patient died from electromechanical dissociation; during ablation a 200 J shock cancelled preexcitation, not being possible to produce reciprocal rhythm. The emergency echocardiography only showed a minimum posterior pericardial effusion. Ablation was effective in 15/23 patients (65%) right posterior paraseptal. Overall success in 1989 (10/27 patients) was 70% (7/10 patients). The success in 1989 was 70% (6/8 patients) right posterior paraseptal. The shortest RP' interval (was 82 +/- 19 msec) during the reciprocal rhythm, where the ablation was performed, was 82 +/- 19 msec (74 +/- 17 msec with success and 99 +/- 19 msec with failure).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236782 TI - [Percutaneous mitral valvulotomy using the Inoue balloon technique]. AB - We have reviewed our initial experience with percutaneous mitral valvulotomy (PMV) in 29 consecutive patients with mitral stenosis using the Inoue mono balloon technique. In all cases, the venous transeptal anterograde approach was used. Age was 49.5 +/- 12.5 years (range 21-78) and only 5 (17%) patients were male. Clinical status was as follows: 15 patients were in NYHA class II, 13 NYHA class III and one in NYHA class IV. Atrial fibrillation was present in 15 (52%) patients and 16 (55%) were on coumarin. An echocardiographic score was employed to assess mitral valve anatomy, parameters including degree of thickening, mobility, calcification and subvalvular involvement were scored independently from 1 to 4. The echocardiographic score so determined was 7.72 +/- 2.1 for the entire group. Ten patients presented mild (+) mitral regurgitation prior to PMV. The mean duration of PMV was 76.2 +/- 29.6 minutes. In only one patient an inadequate positioning of the balloon prevented dilatation of the valve whereas the remaining 28 patients had their valves successfully dilated. Mitral valve area, by means of both Gorlin and Doppler (pressure half time) methods, increased in all cases: from 0.95 +/- 0.17 cm2 to 1.92 +/- 0.31 cm2 (p less than 0.001) and from 0.97 +/- 0.22 to 1.84 +/- 0.33 cm2 (p less than 0.001), respectively. Mitral regurgitation increased angiographically in more than 1 degree only in 1 patient, but no other cardiac or vascular complication occurred. Thus, in our experience PMV with the Inoue mono-balloon catheter is a safe and effective method for dilating mitral valve stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236784 TI - [Natural and unnatural history of the univentricular heart]. AB - We examined the cases of 90 patients found to have univentricular heart at catheterization from January 1971 to January 1988. These patients are the 3.8% of the 2,322 children diagnosed of congenital heart disease by catheterization and angiography in this 17-year period of time. The mean follow-up was 9.5 years. The prognosis is poor: of the 90 patients, 50 died (55.5%) 43 of them in the first year of life. The actuarial survival rate is only the 38.5% at 5 years. Between the 56 children unoperated the mortality rate was the 62.5% and only the 16% (9 patients) survived with good functional results, class I and II of the New York Heart Association. The earlier palliative surgery changes the prognostic and the adverse natural history. The mortality rate in the operated group was the 44.1%. Another 44.1% (15 patients) of the operated group survived, 14 patients in class II and one in class III. The systemic-pulmonary artery shunts are the elective surgical procedure for important pulmonary stenosis, and the Fontan-type procedure is the elective for posterior, definitive repair. PMID- 2236783 TI - [Complete atrioventricular canal and tetralogy of Fallot: surgical considerations]. AB - Nine patients with complete atrioventricular canal and tetralogy of Fallot underwent intracardiac repair of both anomalies between 1982 and 1989. The ages of the patients ranged from 6 months to 7 years. Six of the 9 had one or more previous systemic-pulmonary artery shunts. Two-dimensional echocardiography showed diagnostic characteristics of both malformations in all patients. The diagnosis was confirmed by cardiac catheterization and cineangiography. The ventricular septal defect was repaired by a combined right atrial and ventricular approach in every patient. Outflow tract reconstruction was performed with the use of a transannular patch (4), infundibular patch (4), and a valved conduit (1). There were no hospital deaths. Meningitis was responsible for the death of a patient 2 years after repair. We recommend early palliation, complete repair in those older than 4 or 5 years, surgical technique depending on the anatomical findings, combined atrial and ventricular approach, 2 separate patches to close the ventricular septal defect in required cases, adjusted correction of the right ventricular outflow tract, and careful postoperative care. PMID- 2236785 TI - [Valvular heart diseases (IX). Valvular endocarditis in non-heroin addicted patients]. PMID- 2236786 TI - [A child affected by the Romano-Ward syndrome born of a mother with the Jervell and Lange-Nielsen syndrome]. AB - We report a child affected with the Romano-Ward syndrome (long QT, normal hearing), born from a mother affected with the Jervell and Lange-Nielsen syndrome (long QT plus deafmutism). We discuss the possible pathogenetic reasons for this uncommon association. PMID- 2236787 TI - [Coexistence of two hemodynamically significant mechanisms for syncope associated with glossopharyngeal neuralgia]. AB - Syncope is a rare presentation of glossopharyngeal neuralgia (GN). A patient with squamous cell cancer of the pharynx had GN and syncope due to asystolic pauses and extreme hypotension. The bradyarrhythmias were atropine-sensible, but both this treatment and pacing failed to prevent recurrence of syncopal hypotensive crises, blood pressure continuing to fall during GN attacks. These data suggest that during a neuralgic attack the stimulation excites vagi, causing asystole, and simultaneously abolishes sympathetic tone. Carbamazepine was effective in controlling the symptoms of the patient. PMID- 2236788 TI - [Silent uncomplicated patent ductus arteriosus in children. Diagnosis with echo Doppler]. AB - Three cases are presented of patent uncomplicated ductus arteriosus in children, with short systolic murmur, in which the noninvasive diagnosis could not be possible without the echo-Doppler help. Although are cases with small shunts and hemodynamically well tolerated, its diagnosis and surgical treatment are essential in order to prevent the risk of bacterial endocarditis of those patients. PMID- 2236790 TI - [Patch angioplasty in isolated left main coronary artery stenosis]. AB - A 50 year old male with isolated left main coronary artery disease was surgically treated with saphenous vein patch angioplasty. Surgery results are reviewed by coronariography 2 months later and we comment its use as alternative technique in selected cases. PMID- 2236791 TI - [An informatics program for the management of patients with pacemakers]. AB - We are introducing a software package (Dbase III application) for the management of patients wearing cardiac pacemakers. It runs on any IBM compatible microcomputer with a minimum of 512 Kb RAM and a 10 Mb hard-disk. It works with 6 separate databases: 1) identification-indications; 2) implants; 3) explant closure; 4) follow-up; 5) pacemakers, and 6) electrodes. The program runs completely by menus, tasks being started by one key stroke. The patient databases are structured following the European Pacemaker Patient Card, including its codes. Data introduction is facilitated by friendly screen formats. The pacemaker database contains 495 models and 304 electrodes of all brands. Automatic searches include: 1) hospital number (from last and/or first name); 2) complete pacing history; 3) listing of patients by stimulation mode, loss of follow-up or proximity of expected battery end of life; 4) pacemaker or electrode definition, and 5) pacemaker models contained in the database. The program has been applied by nurses for over 6 months in our service, proving its efficacy with an easier and better follow-up. The accuracy of the automatic searches has been confirmed manually. PMID- 2236789 TI - [Color Doppler study of 2 complicated aortic abscesses ruptured into the right ventricle and left atrium]. AB - This report describes 2 patients with infective endocarditis who subsequently developed aortic abscesses which eventually ruptured, in one case to the right ventricular outflow tract and, in the other, to the left atrium causing, in both patients, severe hemodynamic derangement. The site of communication between the abscesses and the receiving chamber was accurately diagnosed by color flow Doppler imaging which provided more valuable preoperative information than conventional techniques. PMID- 2236792 TI - [Permanent cardiac pacing and the Grupo do Trabajo do Marcapasos]. PMID- 2236793 TI - [Physiological mode of pacing in pediatrics]. AB - The concept of physiologic pacing is often primarily to involve the preservation of atrioventricular synchrony. Nevertheless, specially in children there are other mechanisms different than atrial filling to improve cardiac output such as heart rate increase with exercise. Taking as physiologic pacing those modes of pacing improving hemodynamic condition of the patient we must add to the DDD, the DDDR and SSIR modes of pacing. In this report our experience with 70 consecutive children paced in physiological mode of pacing is described: 51 in SSIR mode, DDD in 16, and DDDR in 3 cases. In five out of the 16 cases with DDD mode it was found an unidirectional crosstalk and in two atrial sensing failure (failure rate with DDD of 47.75% at 48 months of follow-up). In 26 children with rate responsive pacing by means of activity sensing a treadmill exercise test according to Bruce protocol was performed found a significant increase in both, heart rate and maximal work capacity, associated to an improvement in the clinical status and no evidence of arrhythmias in any case. In conclusion, rate responsive pacing by means of activity sensing in children is an adequate, reliable and effective physiological mode of pacing. PMID- 2236794 TI - [Evaluation of DDD and VVIR pacemakers with gated radionuclide ventriculography]. AB - Gated radionuclide ventriculography was performed in 53 patients, with 29 DDD and 24 VVIR pacemakers. Ejection fraction and regional contractility was studied in three conditions: a) At rest. b) With tachycardia after exercise. And c) With induced tachycardia at rest. At a rate similar to the one reached with the exercise. Stimulation in different parts of the right ventricule did not show any differences in the ejection fraction. Induced ventricular stimulation in comparison with natural ventricular contractions did not alter or change ejection fraction if the reached rate was the same an not too high in both cases. Induced stimulation at rest with a rate of 110-120/min, decreased the ejection fraction in 10% (p less than 0.001). Induced stimulation by exercise (VVIR. DDD) increased the ejection fraction in 10% (p less than 0.003) and if there were zones of dyskinesia they improved or disappeared. There were no statistical differences between VVIR and DDD pacemakers. It seems that a limited tachycardia is convenient for patients with rate response pacemakers (VVIR). PMID- 2236795 TI - [Maturation of the electrode-endocardium interface]. AB - It's largely known that the implanted lead in the endocardium develops an inflammation and posterior fibrosis of the cardiac tissue, increasing the stimulation threshold. It's also demonstrated that the chronic threshold values keep relation with the electrode surface area. There are several factors in the fibrosis genesis according mechanical of physical properties of the lead, such as tension, tip design, surface area and the patient reaction to a foreign body. Electrical factor is not yet sufficiently studied. We developed an experimental study in 12 dogs, separated in two groups (four explanted at 8 days or subacute group, and eight explanted at 35 days or chronic group), looking for a correlation between current density crossing the interface endocardial-electrode and the posterior fibrosis. The mechanical factor was minimized by using small surface area electrodes, with little tension. Three leads were implanted in each dog, connected respectively to 0, 2.5 and 5 volts. The simultaneous working of two pacemakers in the same dog, was possible by programming one of them in VVI at 140 per minute, and the other in VOO at 75. The tirht lead was implanted as a reference. The threshold pacing values, in voltage and in current, the R wave and impedance were measured at implant and at explant of the leads. Differences statistically significative were observed between reference electrodes and electrical active ones, according their current density. The leads stimulating with great current density (more voltage) generated more fibrosis and therefore higher pacing threshold values and lower R waves and impedances. The convenience to stimulate at low voltages was seen. PMID- 2236796 TI - [Ambulatory control and follow-up of patients carrying a unicameral pacemaker]. AB - The follow-up schedule after pacemaker implantation should be arranged to allow close monitoring during the immediate post-implant period, and frequent observations during the life of the system. Such follow-up has as major goals the evaluation of the electrical functions of the pacing system to detect malfunctions or imminent power source depletion and the evaluation of the patient cardiac status so that reprogramming can be accomplished. PMID- 2236797 TI - [Comparison between the unipolar and bipolar mode for estimation and detection of auricular and ventricular duration in acute and chronic cardiac pacing]. AB - To add data on controversy between the advantages and inconveniences of using either unipolar or bipolar modes for permanent cardiac pacing, we have studied 15 patients. In all of them a CPI Delta-925 (DDD) pulse generator was implanted. Non invasive pacing threshold values in volts were measured at 0.05, 0.08 and 0.1 ms for each chamber programmed either to unipolar or bipolar mode, at 1, 2, 3, 4, 5, 6, 7, 8, 14, 21, 30, 60, 90, 120, 180 and 365 days after the implant. Sensing thresholds were measured at the same time. For any pulse width the mean pacing thresholds in atrium and ventricle increase uniformly, reaching its maximum values between the days 8 and 14 after the implant and decreases to a stable value between 90 and 120 days after the implant, without statistically significant differences for both: unipolar and bipolar modes. Pacing thresholds (V +/- SD) for 0.05 ms in the day 365th were in atrium: unipolar 2.85 +/- 0.79, bipolar 3.35 +/- 0.92 (p = 0.56) and ventricle: unipolar 3.92 +/- 1.01, bipolar 4.36 +/- 1.35 (p = 0.58). Sensing thresholds in atrium and ventricle decreases from the 1st day after the implant with the minimum mean value the day 8th, increasing eventually. No statistically significant differences were found between sensing unipolar/bipolar mode at each chamber. Sensing thresholds (mV +/- SD) in the 365th day were in atrium: unipolar 4.40 +/- 2.07, bipolar 4.10 +/- 2.10 (p = 0.82) and ventricle: unipolar 11.20 +/- 3.63, bipolar 10.10 +/- 5.13 (p = 0.71). CONCLUSIONS: for every single patient: 1) There are not statistically significant differences in the evolution of unipolar and bipolar pacing thresholds both in atrium and ventricle, regarding rate and time of increase, maximum value, rate of decrease and stable chronic values. 2) There are neither statistically significant differences regarding unipolar and bipolar sensing in atrium and ventricle respect to rate of decrease, time and value of the minimum and stable chronic values. PMID- 2236798 TI - [Sensing anomalies with the VVI pacemaker. Clinical study by Holter]. AB - Defective sensing incidence is controversial. It has rarely been assessed by Holter in series of consecutive patients. Holter was used in 59 cases (84% of implants over 9 months) with a follow-up of between 7 and 19 months. The generators came from 2 manufacturers, 44 unipolar and 15 bipolar, with standard sensitivity level and in VVI with rates covering up the patient's own rythm. Results. Unipolar: all asymptomatic registration and two symptomatic in the follow-up. There were myopotential inhibitions in 31 (70%), but only in 6% lasted over 2,000 msec, there were less than 16 episodes in 94% of cases distributed along the day with an increase between 6 am and 3 pm, and absent from 4 to 6 am. In six (14%) there were inhibitions and reversion to asynchronous.+ pacing with the R on T phenomenon and non conducted artifacts in four; in one case the asynchronous stimulation occurred over sinus rhythm. Undersensing was confirmed in four (9%) but in three was caused by PVC. Bipolar: all were asymptomatic and without sensing anomalies. Conclusions. The high incidence of asymptomatic oversensing in unipolar generators limits Holter's value in the diagnosis of symptomatic cases by myopotential interference. Its routine use for detecting anomalies in sensing seems inadvisable. The reversion to asynchronic functioning is not unusual and could be a potentially provocative mechanism of ventricular arrhythmias. PMID- 2236799 TI - [Permanent atrial stimulation (AAI) in the sick sinus syndrome]. AB - A consecutive series of 18 patients (5 males, 13 females, mean age +/- DS 65 +/- 12 and 66 +/- 13 years, respectively, and mean +/- DS Wenckebach point of 162 +/- 20 ppm) given arterial pacemakers for sinus node dysfunction (SND) were followed to study the incidence of lead failure, atrioventricular conduction disturbances and chronic atrial tachyarrhythmias. The mean follow up time +/- SD was 18 +/- 10 months. There was not lead dislodgement. Chronic voltage output was reduced to 2.5 volts in 73% of patients because of a reduced chronic pacing threshold. One patient presented acute transient rise of pacing threshold and temporary loss of atrial detection. Progression to AV block was not documented. One patient had asymptomatic Wenckebach AV block during the night while on digoxin plus amiodarone. The AV block disappeared after cessation of drug therapy. Patients with previous episodes of paroxysmal atrial fibrillation did not presented the arrhythmia during follow up, while 75% of patients with previous atrial flutter presented the arrhythmia. None of the patients had systemic embolism. In conclusion, AAI pacing is a reliable and safe mode of pacing in patients with SND. PMID- 2236800 TI - [Biosensors and rate-responsive cardiac pacing]. AB - Patients with atrioventricular block and ventricular pacemakers at a fixed rate have their exercise ability limited. This situation has been solved through dual chamber pacing in those patients keeping an adequate sinus node function. For the remaining, showing chronotropic failure or atrial fibrillation, the ability to increase their pacing rate is only possible when signals other than atrial activity, and reflecting metabolic needs, are used as a guide. These signals detected by a sensor, act through an algorithm modifying the pacing rate and are the cornerstone of rate-responsive pacing. Indications for these stimulation modes are analyzed as so are characteristics of different sensors used for this aim (pH, respiratory rate, QT interval, body activity, minute respiratory volume, central venous pressure, preejection period + stroke volume, right ventricular dp/dt, evoked QRS response and venous oxygen saturation). PMID- 2236801 TI - [Escape rhythms after ablation of the atrioventricular junction and implantation of a pacemaker]. AB - Escape rhythms characteristics after successful catheter ablation of the atrioventricular junction and intentional complete heart block were compared with those due to others etiologies as well as the advantage of the posterior implantation of a rate responsive pacemaker (VVIR). In 22 patients, 9 men and 13 women, with permanent AV block after fulguration and follow-up periods from 4 to 58 months, escape rhythms data studied during the procedure and at short and long term periods, showed the following characteristics: 1) Classical parameters of valuation are not as a whole useful to evaluate subsidiary escape rhythms after electrical fulguration of the atrioventricular junction system. 2) The QRS morphology of the escape rhythm exhibited frequently right or left bundle branch block and specially the former. 3) Spontaneous variability of the escape rhythm recovery time makes this parameter unreliable. 4) Electrophysiological parameters previous to the shock and energy delivery do not predict the origin and characteristics of the subsidiary escape rhythms. 5) Active ventricular arrhythmias appearing immediately postshock are unrelated with any subsequent complication. 6) Permanent pacing increases pacemaker dependency at least temporarily. In 15 of 22 patients, a rate responsive multiprogrammable pacemaker controlled by QT interval was implanted. Cardiac performance and life-quality was improved in these patients due to the addition of several factors: 1) Control of the tachyarrhythmias. 2) Elimination of antiarrhythmic drugs and their side effects on ventricular function. 3) Self-regulation of cardiac rate through permanent stimulation with a QT sensitive rate responsive pacemaker. PMID- 2236802 TI - [Hemodynamic benefits of AV interval adjustment and heart rate increase during exercise in dual-chamber pacing as determined by Doppler]. AB - In order to determine the relative significance of ventricular rate increase and AV delay on exercise cardiac output, we have studied 10 patients (8 male and 2 female, 16-59 years) with complete chronic heart block treated with AV sequential pacing. Cardiac output variations (delta CO) were estimated by pulsed Doppler comparisons of the aortic flow velocity in the supine position, at rest and during bicycle exercise. The following pacing programs were tested: DDD with AV intervals of 50, 100 and 150 ms (DDD50 o DDDD100, DDD150), VVI at 70 ppm (VVI70), and VVI at the maximal available rate in this pacing mode-113 or 130 ppm depending on the PM type (VVIM). Exercise measurements in DDD mode were taken when that rate was reached. The delta CO was calculated as a percent change of the product flow velocity integral x heart rate, from that obtained with VVI70 mode at rest. At rest, the delta CO obtained with DDD pacing was 20.4 +/- 14.7% and the optimal AV delay was 50 ms in 1 patient, 100 ms in 3 patients and 150 ms in six. During exercise, the delta CO was higher in DDD and VVIM modes (82.0 +/- 30.8% and 56.2 +/- 37.6%, respectively; p less than 0.01) than in VVI70 mode (20.4 +/- 10.4%; p less than 0.005), the greatest delta CO was reached at DDD mode in 8 out of 10 patients (p less than 0.03). The optimal AV delays were 50 ms in 5 patients, 100 ms in 4 patients and 150 ms in one. Thus, DDD pacing with the optimal AV delay seems to obtain greater haemodynamic benefits during exercise than does rate-responsive pacing; the optimal exercise AV delay varies from patient to patient and is usually less than 150 ms. PMID- 2236803 TI - [Experience with dual-chamber pacemakers at the Valencia General Hospital]. AB - We report our experience with dual chamber pacemakers in 70 patients (mean age 64.5), of whom 42 had AV block and 28 sick sinus syndrome, nine of them associated with AV block. Other cardiac disease coexistent with the conduction disturbance was present in 57% of the patients. Follow-up was conducted after implantation at first, 3rd, 6th month, and thereafter each 6 months. Mean follow up was 20 +/- 14.3 months (2-72); of the 70 patients, 88% and 73% were followed at least for 6 and 12 months, respectively. Six patients (five had AV block) died 17 months on average after implantation. All patients but one had concomitant cardiac disease. Eleven patients (15.6%) presented complications, being all of them related to atrial channel: reprogramming to VVI in five (7%), mainly due to chronic atrial fibrillation (4 patients), whereas in the other one was secondary to loss of pacing and sensing functions; acute dislocation corrected with reoperation in 3 patients (4.3%); temporary loss of atrial sensing in 2 patients, and chronic in the last one, with change to DVI mode. Overall, considering deaths and changes to VVI mode, 15.6% of patients were not be able to maintain dual chamber pacing. In conclusion, our results show: 1) low rate of major complications; 2) good outcome of patients suffering from sick sinus syndrome; 3) the development of chronic atrial fibrillation was the main limitation of DDD pacing system. PMID- 2236804 TI - [Anterograde tachycardia caused by the antitachycardia mechanism in a DDD pacemaker]. AB - If there is a demonstrable ventriculo-atrial conduction at the time of a DDD pacemaker implantation, the possibility of a pacemaker mediated tachycardia is always present. The latest technological advances tries to solve this problem by the refractory time programmability and specially by the automatic extension of the atrial refractory period. A new and special mode of premature ventricular contraction-synchronous atrial stimulus has been developed as an additional and more effective mechanism anti pacemaker mediated tachycardia. We present one case in which this anti pacemaker mediated tachycardia mode just unchains one tachycardia. The understanding of this tachycardia doesn't offer difficulties and the correction would be made by different steps. PMID- 2236805 TI - [Clinical experience and long-term results of antitachycardia pacemakers in patients with supraventricular tachycardia]. AB - Patients with episodes of recurrent paroxysmal supraventricular tachycardia, refracted to different pharmacologic therapies, can be treated with automatic antitachycardia pacemakers. Long term results of 8 patients (6 females and 2 males), mean age 49.8 +/- 12.7 years, are presented. There were implanted an antitachycardia pacemaker 262-12 Intertach, with an electrode in right atrium. Electrophysiologic study showed a node reentry mechanism in 6 cases due to AV node functional dissociation; one case of accessory concealed pathway and other case with a double accessory pathway was undetected in the electrophysiologic study and it was the unique case in which the pacemaker was explanted due to their inefficiency. Every tachycardia were orthodromic with narrow QRS wave and mean cycle was 361 +/- 23 msec (range 310-400 msec). One case had two types of tachycardia, one with narrow QRS wave and other wide QRS wave tachycardia and different length of cycle what reduced to detect a previously double pathway. A reoperation was necessary in one case due to an electrode displacement and, finally, another one needed a reprogramming auricular sensitivity. Mean time follow-up was more than 2 years. Seven patients have sinusal rhythm without drugs and they have 6 months follow-up with a better quality of life, less hospital incomes and medical cares. PMID- 2236806 TI - [Sleep apnea syndromes and the pathology of respiratory disorders during sleep]. PMID- 2236807 TI - [The physiology and pathology of sleep]. PMID- 2236808 TI - [The upper airway and respiratory disorders during sleep]. PMID- 2236809 TI - [The role of respiratory muscles in the interruption of the obstructive sleep apnea]. PMID- 2236811 TI - [Diagnosis of sleep apnea syndrome]. PMID- 2236810 TI - [Polygraphic registration during sleep]. PMID- 2236812 TI - [From snoring to sleep apnea syndrome]. PMID- 2236813 TI - [From sleep apnea syndrome to chronic respiratory insufficiency and right cardiac effects]. PMID- 2236814 TI - [The epidemiology of sleep apnea syndrome in adults]. PMID- 2236815 TI - [Surgical treatment of sleep apnea syndrome]. PMID- 2236816 TI - [Instrument treatment of sleep apnea syndrome]. PMID- 2236817 TI - [The medical treatment of sleep apnea syndrome]. PMID- 2236818 TI - [Respiratory pathology during sleep in children]. PMID- 2236819 TI - [Hypoxemia of chronic obstructive bronchopneumopathy and sleep]. PMID- 2236820 TI - Perspectives and limits in the eradication of infectious diseases. AB - Eradication of an infectious disease on a global scale means that transmission of the disease has been completely vanished and the disease caused by the infection has totally disappeared. Regional eradication represents disappearance of an infection from a certain area or region whereas elsewhere it continues to be transmitted. Smallpox which was finally eradicated in 1977 had been progressively eliminated from one continent after another in the preceding years. At the present time regional elimination of paralytic poliomyelitis has almost succeeded in the USA, the United Kingdom, Europe and Asia through routine use of Sabin live oral vaccine. Paralysis associated with the use of this vaccine has continued with an extremely low incidence-rate. Contact-infection and spread of virus excreted by recently-vaccinated persons occur to a significant extent and fortunately with polioviruses mostly unchanged in virulence. The second disease with attempted regional elimination is measles. In the USA county-wide elimination was successful in 1985 in all but a minority of counties. There followed two years with many more cases before a decline in incidence resumed once again. Elsewhere the general sponsoring of immunization under the expanded programme (EPI) of WHO is slowly taking effect. PMID- 2236822 TI - [A clinico-epidemiological study on the efficacy of thymopentin therapy in patients with chronic bronchitis and cellular immunity deficiency]. AB - The immunological in vivo effects of thymopentin (TP5) treatment in eleven hypo anergic patients affected with chronic bronchitis are reported. Significant improvement of cellular immunity, evaluated by skin tests, and an increase of percentage of CD4+ cells and natural killer activity are demonstrated. The clinical evaluation showed an evident reduction of infectious episodes of acute bronchitis after TP5 treatment. PMID- 2236821 TI - [The new aspect of pneumonia in an area of the Middle Adriatic]. AB - The present work reports the findings of a ten-year, research, the aim of which is to outline current views of pneumonia in a zone of the Middle Adriatic (USL 17 Regione Marche). The study confirmed, in its entirety, a lesser aggressiveness and loss of the "seasonal feature" of today's pneumonias. The high incidence of Atypical Pneumonia (AP) due to viral-like microorganisms (mycoplasma, chlamydia, coxiella, legionella) and an even higher one of unknown etiology is reported. After having analysed the most likely reasons for such a change and its various implications, the authors conclude that this type of research should be extended in order to trace a map of the more common infectious agents in single geographical zones, as an indispensable premise for a more concrete etiological diagnosis and for a more rational choice of the antibiotic. PMID- 2236823 TI - [Abdominal lymph node tuberculosis: a diagnostic surprise]. AB - The case of a patient submitted to sonographic abdominal examination because of recent onset of fever, abdominal pain and weight loss, with the finding of multiple enlarged lymph nodes along great vessels, is reported. Because of the negativity of noninvasive procedures, the patient underwent laparatomy and biopsy. The histologic and bacteriologic diagnosis of tuberculous lymphnodes was unexpected, as the patient was unreactive to the tuberculin skin test and had no signs of active pulmonary tuberculosis. Although uncommon, tuberculosis must be included in the differential diagnosis of subdiaphragmatic lymphadenopathies even if symptoms of mycobacterial infection or other signs of the infections are not presented. PMID- 2236824 TI - Search of HIV DNA by polymerase chain reaction in the urine sediments of seropositive individuals. AB - We have utilized the polymerase chain reaction (PCR) technique to detect proviral sequences of the human immunodeficiency virus (HIV) from urine sediments of HIV seropositive individuals. HIV amplified DNA sequences, easily detectable in peripheral blood cells, were not found in the urine sediments of the seropositive individuals. This finding is in agreement with previous observations that the urines of seropositive individuals are not infective. PMID- 2236826 TI - [Pulmonary and tonsillar distribution of ceftriaxone and cefonicid and the resultant bactericidal activity of the organ]. AB - The therapeutic efficacy of Ceftriaxone and Cefonicid 1 g I.M. single-dose against S. Pneumoniae, H. Influenzae and K. Pneumoniae in tonsil and lung infections was studied using bactericidal quotient (BQ). Samples of lung tissue and serum were obtained from two groups of surgical patients, treated with Ceftriaxone or Cefonicid 1 g I.M., 2-8-16 and 24 hours before surgery. From two other groups of 10 surgical patients, treated as above, samples of tonsil tissue and serum were obtained. In lung tissue the higher levels of Ceftriaxone and Cefonicid appeared at the second hour (11.54 +/- 1.59 mcg/g and 11.4 +/- 2.49 mcg/g respectively); the lower values were observed at the 24th hour (2.18 +/- 0.47 mcg/g for Ceftriaxone and 0.64 +/- 0.21 mcg/g for Cefonicid). Higher Ceftriaxone and Cefonicid levels also appeared in tonsil tissue at the 2nd hour (11.12 +/- 2.42 mcg/g and 9.22 +/- 3.12 mcg/g respectively); the lower values were observed at the 24th hour (1.54 +/- 0.46 mcg/g for Ceftriaxone and 0.42 +/- 0.23 mcg/g for Cefonicid). BQ values were estimated using the ratio between the mean concentrations of Ceftriaxone and Cefonicid in tissue samples and the MBC mean values determined for the above mentioned pathogens, isolated in hospital. Ceftriaxone always showed BQ values greater than 1 during 24 hours versus levels observed for the three reported pathogens. Cefonicid showed BQ values greater than 1 during 24 hours against S. Pneumoniae and BQ values less than 1 for 6-8 hours against H. Influenzae and for 1-4 hours against K. Pneumoniae. PMID- 2236825 TI - Empiric antibiotic and antifungal therapy for granulocytopenic patients with acute leukemia. AB - A prospective study was undertaken to determine the effectiveness of an empiric antibiotic treatment employing the combination of a beta-lactam and an aminoglycoside followed in non responders by vancomycin and amphotericin B after 48 and 96 hours respectively. We have evaluated 180 febrile episodes in 102 granulocytopenic leukemic patients. Febrile episodes (44%) were microbiologically documented; 29% were only clinically documented and 27% were possible. In the 180 evaluable episodes treated with a beta-lactam and an aminoglycoside the overall response rate was 61%. In non responders the addition of vancomycin increased the response rate to 83% and the subsequent addition of amphotericin B moved the total responders to 96%. Antibiotic related side effects were minimal. These data suggest the importance of an empiric strategy for treatment of bacterial infections arising in granulocytopenic patients. An early empiric antifungal therapy also appears necessary to control clinically undetected fungal invasion. PMID- 2236827 TI - [Disulfiram-like effect of cefonicid: first observation]. AB - The disulfiram-like reaction is linked to the assumption of ethyl alcohol during therapy with the cephalosporin latamoxef, cefamandole and cefoperazone. The reaction is commonly ascribed to the methyl-thiotetrazole group, resembling part of the disulfiram molecule. We describe the case of a patient who experienced on two different occasions a disulfiram-like effect during therapy with cefonicid. This cephalosporin contains the methylsulphothiotetrazole group in place of the methylthiotetrazole group. Our observation is the first related to cefonicid. PMID- 2236828 TI - [Clinico-hematological evaluation of 57 patients undergoing antiaggregant treatment with indobufen]. AB - A long-term administration of Indobufen, 400 mg daily, was evaluated in 57 patients with cardiovascular diseases. Aggregation waves induced by ADP, collagen and epinephrine showed a significant and persistent inhibition of platelet function. Minor side effects were observed and in 6 patients the drug was withdrawn: 4 patients began to experience gastric troubles, 1 patient had positive occult test for blood, 1 patient developed an allergic rush. Clinical evaluation and platelet aggregation study before starting indobufen and during the follow up period seem to be useful in the evaluation of effectiveness, safety, compliance and suitable daily dose. PMID- 2236829 TI - [Severe hemorrhagic thrombopenia during epidemic rubella. Description of 2 cases]. AB - The authors describe two cases of severe hemorrhagic thrombocytopenia during epidemic rubella. They evaluate the pathogenetic mechanisms. PMID- 2236830 TI - [Professional responsibility of the hospital physician]. PMID- 2236832 TI - Hormone-related malignant tumors. PMID- 2236831 TI - [Tuberculosis and mycobacteriosis in HIV-1 infection]. AB - Tuberculous and mycobacterial infections and diseases increase now everywhere. Patients HIV-1 infected or with AIDS get more and more a mycobacterial complication. The clinical and radiological features of this event are: the bilateral extension in the lung, the importance of these lesions, the atypical appearance of radiological shadows, the frequency of other concomitant opportunistic pneumopathies of non-mycobacterial origin. Tuberculosis are almost always induced by drug-sensible mycobacteria which usually allows clinical healing or clinical improvement. PMID- 2236833 TI - Adrenocortical tumors: clinical and diagnostic findings. PMID- 2236834 TI - Contributions of nuclear endocrinology to the diagnosis of adrenal tumors. PMID- 2236835 TI - Aspects of surgical therapy of adrenal tumors. PMID- 2236836 TI - Molecular biology of the male endocrine system. PMID- 2236837 TI - Development of hormone refractory tumors: adaption versus clonal selection. PMID- 2236838 TI - Localization of hormones by antibodies. PMID- 2236839 TI - Basic and clinical relevance of hormonal influence in breast cancer. PMID- 2236840 TI - Hormonal therapy in endometrial carcinoma. AB - Although hormonal agents have been used to treat endometrial cancer for nearly 30 years, response rates have remained essentially unchanged. Furthermore, objective response rates vary considerably from institution to institution, presumably because of differences in accepted response criteria and patient selection. The latter is particularly influenced by the distribution within the treated population of well-differentiated and poorly differentiated tumor histologic types. Nevertheless, the rapid attrition after hormonal therapy begins and the limited long-term salvage in nonselected patients with advanced primary or recurrent disease suggest primary nonresponsiveness or acquired tumor refractoriness to hormonal therapy. The determination of tumor progesterone receptor levels has made it easier to identify patients with sensitivity to such therapy. Recent investigations have shown favourable response rates (72%) after administration of progestational agents in patients with progesterone receptor rich tumors. Similarly, responses have been reported with antiestrogens and combination progestin-antiestrogen therapy, recent laboratory observations having suggested potential benefit from sequential administration. Although these clinical and laboratory findings are encouraging, the limited duration of objective responses and the poor long-term survival rates continue to temper enthusiasm for routine hormonal therapy. Properly stratified (according to pathologic, biochemical, and clinical criteria), prospective, randomized, double blind studies with more definitive end points, such as progression-free survival and overall survival, are mandatory to further evaluate the merits of various therapeutic regimens using gonadal hormones. PMID- 2236841 TI - Hormone-secreting ovarian tumors. PMID- 2236842 TI - Ovarian hormones and carcinoma of the uterine cervix. PMID- 2236843 TI - Tumours of the adrenal gland. PMID- 2236845 TI - Advances in breast cancer detection. The Fourth International Copenhagen Symposium. Copenhagen, August 1988. Proceedings. PMID- 2236844 TI - Clinical and diagnostic findings in patients with chromaffin tumors: pheochromocytomas, pheochromoblastomas. PMID- 2236847 TI - Earlier detection of breast cancer: an overview. PMID- 2236848 TI - Stereotactic, X-ray guided, fine needle aspiration biopsy of nonpalpable breast lesions: comparison with the coordinate grid localization technique. PMID- 2236846 TI - Relative doses in mammography: the future development of film/screen mammography systems. PMID- 2236849 TI - Stereotactic breast puncture: an indispensable complement to the detection of breast cancers within the framework of a screening program. PMID- 2236850 TI - Stereotaxic fine needle aspiration of nonpalpable breast lesions with the cytoguide unit: first experiences. PMID- 2236851 TI - Preoperative diagnostic and prognostic information on nonpalpable breast tumors. PMID- 2236852 TI - Why and by whom are patients referred for mammography? PMID- 2236853 TI - Imaging techniques other than mammography for the detection and diagnosis of breast cancer. PMID- 2236854 TI - Breast ultrasound in the detection of breast cancer. PMID- 2236855 TI - A new method for assessment of radiation risk from screening mammography. PMID- 2236856 TI - Should breast self-examination be included in a mammographic screening program? PMID- 2236858 TI - Inflammatory disease of the breast. PMID- 2236857 TI - Imaging the breast treated by segmental mastectomy and irradiation. PMID- 2236859 TI - Stellate lesions of the breast. PMID- 2236860 TI - Screening for breast cancer: opportunities, status and challenges. AB - Screening mammography and physical examination have made major contributions to the earlier detection of breast cancer. Mammography is the only reliable means of detecting nonpalpable cancers and can detect many minimal breast cancers when they appear to be curable. Low-cost, high-quality mass screening mammography, accurately interpreted, is feasible and could reduce overall mortality from breast cancer if it were more widely applied. Recognition of the need and desire to provide the service are essential initial motivating factors. The challenge to radiology is to obtain sufficient competent personnel and facilities. PMID- 2236861 TI - Follow-up studies of the health insurance plan study and the breast cancer detection demonstration project screening trials in the USA. PMID- 2236862 TI - Low-cost mass screening as a means of reducing overall mortality from breast cancer. AB - Mammography is a screening method that has been proven effective and could significantly reduce the overall mortality from breast cancer if it were more widely applied. The challenge to radiology is to provide sufficient competent personnel and adequate facilities such that reproducibly optimal screening mammography, accurately interpreted at the lowest possible cost, is made widely available. PMID- 2236863 TI - Screening for breast cancer with mammography in Bohuslan County, Sweden. AB - The unique organization of breast cancer screening in Bohuslan, using a specially designed mammography bus, has allowed women from a relatively large area to be screened for breast cancer. The cooperation with radiologists and surgeons at the central hospitals in the county is very positive and interesting. As can be appreciated, this is a very streamlined and efficient operation. So far, we have arrived at the same results as pilot investigations in other counties. PMID- 2236865 TI - Quality requirements in mammographic screening in Sweden. PMID- 2236864 TI - Evaluation and comparison of mammographic quality at facilities participating in a regional breast cancer awareness program. PMID- 2236866 TI - One versus two views per breast for screening mammography. PMID- 2236867 TI - Mammographic features of malignancy found during screening. AB - Mammographic detection of nonpalpable breast cancer permits earlier diagnosis and reduces mortality from the disease. The increasing emphasis on screening asymptomatic women with mammography is placing the responsibility for tumor detection more and more in the hands of the radiologist. While it has long been known that cancer can present mammographically with less than textbook features of malignancy, it has only recently become apparent that this occurs frequently among nonpalpable neoplasms, just those tumors that we must discover by screening. Radiologists must learn to search carefully, not only for characteristic tumor masses and clustered calcifications, but especially for the more subtle and indirect signs of malignancy. PMID- 2236868 TI - Breast cancer screening in Iceland: preliminary results. PMID- 2236869 TI - Role of epidemiology in health risk assessment. AB - Human health risk assessment has been the object of systematic study in recent years, with formal models of risk assessment and risk management having been proposed by several national and international health agencies. The particular model developed by the Environmental Health Directorate of Health and Welfare Canada was examined in some detail and used to focus on the role of epidemiology in the overall process of risk assessment. In addition to providing information fundamental to the identification of environmental carcinogens and the estimation of carcinogenic risks, epidemiology may also play a role in shaping risk perception and in improving risk communication practices. Taken collectively, epidemiologic data on health risks provide a basis for improved disease surveillance and prioritization of public health concerns. Both descriptive and analytic epidemiologic protocols may be used to gather information on disease etiology. Because of the potential for bias and confounding in observational studies of human populations, epidemiological data should be subjected to careful evaluation in accordance with established criteria before a causal relationship between exposure and disease is inferred. Toxicological studies using nonhuman test systems may be used to avoid these problems, but at the expense of obtaining indirect information on human health risks. Nonetheless, toxicological data provide an important complement to epidemiological data, providing information on potential health risks in advance of human exposure and offering a means of indirectly assessing risks in situations where human studies fail to provide informative results. The complementary roles of epidemiology and toxicology in health risk assessment were examined using four case studies. While the epidemiological evidence linking tobacco consumption to lung cancer is now unequivocal, the corresponding data on involuntary smoking, although strongly suggestive of increasing the relative risk of lung cancer, requires further confirmation before providing the same degree of evidence as now exists for active smoking. At present, the best estimates suggest that overall mortality attributable to active smoking may exceed that due to passive smoking by roughly 100-fold. Despite this large difference in health impact, passive smoking continues to be the focus of much public concern, in part because of the involuntary nature of the risk involved. Because of the abundance of good epidemiological data on tobacco, toxicology has assumed a secondary role in defining the health risks associated with smoking. In contrast, while epidemiological studies with saccharin and formaldehyde have provided unequivocal evidence of carcinogenic effects in animals exposed to high doses, thereby raising concerns over potential human carcinogenicity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2236871 TI - Cancer risks due to asbestos and man-made fibres. PMID- 2236870 TI - Identification of occupational cancer risks using a population-based cancer registry. AB - The study of Xuan Wei fuel use and lung cancer mortality and also the interim case-control study suggested an association between domestic smoky coal use and Xuan Wei lung cancer. The collaborative studies of physical characterization, chemical analysis, and toxicology further substantiated this linkage. The Xuan Wei residents who used smoky coal inhaled extremely high concentrations of mostly submicron-sized particles, which can be inhaled and deposited effectively deep in the lung. These fine particles were composed mostly of organic compounds (72%), including mutagenic and carcinogenic organic compounds, especially in the aromatic and polar fractions. These residents were exposed to polycyclic aromatic compounds, such as benzo[a]pyrene, at comparable or higher levels than those measured in coke oven plants and other occupational environments (International Agency for Research on Cancer 1984). In comparison with wood and smokeless coal combustion emissions, the organic extracts of smoky coal emission particles showed much higher activity of genotoxicity and carcinogenicity. These results all point to a strong etiological link between the complex organic mixtures from smoky coal emissions and Xuan Wei lung cancer. This study and studies reported by other investigators (de Koning et al. 1984) suggested little association between indoor open-fire wood smoke and lung cancer. The less efficient lung deposition of the larger particles from wood combustion, as well as the lower concentrations of biologically active organic compounds, may contribute to the low rate of lung cancer in the wood-burning communes. As to the smokeless coal emissions, the lower particulate concentration and the lower organic content of the particles emitted may also contribute to the low lung cancer rate in the commune using this fuel. In conclusion, the complex organic mixtures from combustion emissions are genotoxic and carcinogenic in animal and in vitro assays. The magnitude of the cancer risks from the complex organic mixtures in man depends on the degree of the exposure, the types of the compounds contained in the mixtures, and the concentrations of these biologically active compounds present in the combustion emissions. PMID- 2236872 TI - Herbicides and cancer: a review and discussion of methodologic issues. PMID- 2236873 TI - Cancer risks from exposure to radon progeny in mines and dwellings. PMID- 2236874 TI - Cancer risks due to exposure to electromagnetic fields. PMID- 2236875 TI - Human lung cancer risks due to complex organic mixtures of combustion emissions. PMID- 2236876 TI - Discovering occupational carcinogens in population-based case-control studies: review of findings from an exposure-based approach and a methodologic comparison of alternative data collection strategies. PMID- 2236877 TI - Recent approaches to retrospective exposure assessment in occupational cancer epidemiology. PMID- 2236878 TI - Effects of measurement errors on estimates of exposure-response relationships. PMID- 2236879 TI - Adjustment for confounding in occupational cancer epidemiology. PMID- 2236880 TI - Statistical issues in the analysis of data from occupational cohort studies. PMID- 2236881 TI - Towards an automated micronucleus assay as an internal dosimeter for carcinogen exposed human population groups. PMID- 2236882 TI - Keep the fire burning. PMID- 2236883 TI - Stressors and stress management--1 month after myocardial infarction. AB - Stressors and stress management behaviors reported by 52 myocardial infarction (MI) patients were identified from a content analysis of transcriptions of nurse/patient/spouse interactions that took place 30 days postinfarction. Subjects defined stress primarily in terms of distress related to appraisals of harm, loss, or threat. Stressors and stress management behaviors varied, although subjects were similar in age and occupation and were in the same phase of recovery. Most stressors related to recent myocardial infarction and pertained to thoughts and feelings more than to external events. Others, related to family and/or work, were ongoing before the MI. Stress management behaviors comprised a continuum of physical, cognitive, and verbal behaviors ranging from active to passive. Avoidance of situations, ignoring situations, expressing feelings, and thinking things through were the four major modes of stress management behaviors. Implications for rehabilitation nursing practice are identified. PMID- 2236884 TI - The self-help movement in head injury. AB - The purpose of the research project reported in this article was to describe head injury support groups and compare them to other types of self-help groups. A 21 item questionnaire inquired about the impact, benefits, and description of the support group selected for study. Seventy-seven members of four randomly selected state chapters of the National Head Injury Foundation (NHIF) answered the survey. Eighty-two percent of the members felt that their membership was helpful in their adjustment. The perceived benefits of the groups were (a) to obtain information on head injury; (b) to be with others who were experiencing the same ordeal; (c) to increase awareness about head injury; and (d) to learn about available resources. PMID- 2236885 TI - Bowel continence for the child with a neurogenic bowel. AB - For more than 10 years, the Alfred I. duPont Institute's Spinal Dysfunction Clinic in Wilmington, DE, has helped families and their children with myelomeningocele and neurogenic bowels to establish workable, acceptable, physiologically sound bowel programs. The basic bowel management program at the Alfred I. duPont Institute is described here, as is a program by which a child with a neurogenic bowel can obtain continence. The program is based on the child's developmental level, physiological abilities, and any necessary pharmacologic intervention. The program has enabled approximately 75% of its child patients over age 5 with neurogenic bowel to be continent of stool. PMID- 2236886 TI - Heparin lock for nighttime intravenous fluid management in a dysphagic patient. AB - Dysphagia, with its inherent risk of aspiration, is a clinical problem frequently encountered in patients with brain injury from trauma or cerebrovascular accident. The use of nasogastric tubes and intravenous lines for nutrition and hydration can be cumbersome and uncomfortable for the patient, and can interfere with rehabilitation therapy. With the advent and increased use of video- and cinefluoroscopy to evaluate swallowing, the type of dysphagia can be defined more readily. This article describes the use of a heparin lock at night to provide fluids intravenously to a patient who could swallow solid or semisolid food, but aspirated thin liquids. This approach insured adequate hydration while keeping the patient free of parenteral lines and nasogastric tubes during therapy. This technique was continued for 3 1/2 weeks until the patient's dysphagia improved and a full oral diet could be resumed. The authors recommend the use of nighttime intravenous feeding via a heparin lock as an option for managing this subset of dysphagic patients in a rehabilitation setting. PMID- 2236887 TI - Roles of a new rehabilitation director of nursing. PMID- 2236889 TI - Need for pediatric content. PMID- 2236888 TI - The Neuman Systems Model: an analysis of a clinical situation. PMID- 2236890 TI - [What has spinal stabilization contributed for the paraplegic patient?]. AB - The aim of spondylodesis is to restore the injured spinal column to its previous shape and stability. In the transverse SCI patient, it entails easier intensive care in case of multiple injury as well as easier general nursing tasks, and greater intensity of physiotherapy in the acute and early phases. Compared to conservative management of the injured spinal column, mobilization is effected some 21 to 39 days earlier in surgical patients, total hospitalization in tetraplegics is shortened by 5 days, and by 34 to 57 days in paraplegic patients. Functionally valuable neurological recovery in primary complete paralysis occurs in 19%/20% of conservative/surgical cases, in primary partial paralysis in 67%/58%. Stabilization of the spinal column however does not at the same time achieve a stabilization of the transverse SCI patient's entire situation- physical, psychological, social. Irrespective of the scope of paralysis, the advantages of a spondylodesis should be considered also in case of total paraplegia. Conservative management retains its importance in cases where surgery is not indicated, or even contraindicated. Comparable results are very rarely achieved outside the specialized centres. Acute cases of SCI should therefore be referred to spinal centres as soon as possible, which for their part have to be able to admit patients 24 hours a day, as well as to provide adequate care until completion of the entire treatment. PMID- 2236891 TI - [Vocational rehabilitation of psychiatrically handicapped people]. AB - The article describes the working concepts of "Lankwitzer Werkstatten", a facility for vocational rehabilitation of persons with (chronic) mental illness. The working concept of this sheltered workshop is crafts- and service-oriented. Some 60 rehabilitees and sheltered workshop employees work in four small "shops". Work structures and everyday organization are somewhat unusual in that they follow general labour market conditions as closely as possible. In their working structures, the sheltered workplaces usually do not differ from workplaces in small crafts enterprises of the general labour market. As far as remuneration is concerned, the workshop is in a position to at least envisage levels of pay that will ensure independence from social assistance supplements if the facility's technical equipment can be kept current and work planning made more efficient. Within the limits of the legal possibilities, and making the most of them, both the diagnostic-prognostic benefits of the entry procedure in the work training process as well as the placement opportunities for rehabilitees in the general labour market are being utilized, with occasionally very successful outcomes. PMID- 2236892 TI - [Didactic problems of education and instruction of patients with craniocerebral trauma]. AB - While concepts for the solution of didactical-methodological problems are available for brain-injured children and young people, such concepts are almost nonexistent for adults with craniocerebral trauma sequels. A case example is presented from an educationist perspective, illustrating the disruptive impact of craniocerebral trauma on the person's biography. Didactical and methodological problems not only arise from deficient cognitive functioning but also due to the psychosocial impact of severe brain trauma. Inter alia dealt with is the question of whether an independent didactical approach is needed, or whether concepts derived from general didactics can be applied. For learners with craniocerebral trauma, "learning theory-based didactics" is an especially suitable model; a brief description is given, and its application to the specific situation of this population outlined. People with brain trauma display problems in knowledge acquisition and concept formation (cognitive learning), in transfer of learning content and performance control. Though an independent didactical concept may not be necessary, it is however crucial that in respect of the teaching/learning processes in this population, due attention is being paid to methodological principles applied in the special education field. PMID- 2236893 TI - [The state of professional psychological guidance for patients with multiple sclerosis]. AB - Over a period of two years, a total of 847 patients with multiple sclerosis (283 male and 564 female aged 18 to 79 years) were interviewed relative to the psychological care provided. Two patients currently participated in regular client-centered group therapy, 11 patients had regularly attended individual or group psychotherapy in previous years, and one patient had undergone family therapy several years ago. Another 26 patients reported occasional supportive counselling by their neurologist or family doctor in the framework of outpatient care. Ten patients used relaxation techniques such as autogenic training, and 42 patients reported emotional benefit from contacts within an MS self-help group. The findings of our study show that professional psychological care of persons with MS is extremely sparse, substantiating the call for better psychological services in coping with MS. PMID- 2236894 TI - Interregional elderly migration and population redistribution in four industrialized countries. A comparative analysis. AB - Though differing in cultures, languages, and socioeconomic attributes, the industrialized nations of the world share a common characteristic: relatively low fertility levels and relatively high proportions of elderly people. These elderly persons are not spread uniformly across their national territories; they exhibit distinct population geographies. This article examines the elderly migration and population redistribution process in four industrialized countries, identifies their principal retirement regions, and analyzes the sources of regional elderly population growth in these regions. It concludes that the United Kingdom and the United States are approaching the final stages of their "elderly mobility transition," whereas Japan is only entering the first stage, with Italy occupying a position somewhere in between. PMID- 2236895 TI - The experience of micro- and macroevents. A life span analysis. AB - This study investigated how individuals retrospectively construe their lives in terms of major life events. Ninety-nine participants sorted a set of personal and historical events in terms of perceived importance for their lives. Analyses of variance with repeated measures and rank comparisons were computed. Overall findings revealed no cohort differences with regard to the perception of life events. However, within-cohort differences were found, indicating that more life events were recalled from the young adult years. Those experiences were also perceived as having been more important in the participants' lives than events from other age segments. With regard to historical events, war-related experiences were among the highest ranked. Analyses of variance revealed intracohort differences but not intercohort differences, indicating higher scores for the time between 1930 and 1948 relative to other historical periods. PMID- 2236896 TI - Feasibility and efficacy of verbal consents. AB - Refusal rates for participation in geriatric research have been surprisingly high. This may be due in part to inherent difficulties with a written consent procedure. A simple, easily administered, standardized verbal consent procedure (VCP) for the institutionalized elderly was developed to address this problem. Of 114 patients eligible for enrollment in a study evaluating outcomes of group psychotherapy, 100 gave verbal consent. When written consent was requested, 60 signed immediately; 35, only after substantial coaxing. Five patients refused to sign a consent form, although verbally agreeing to participate. It is estimated that the number of study participants would have been reduced by 40% had written consent been required. The findings raise ethical and logistical issues pertaining to a verbal consent procedure. PMID- 2236898 TI - In vivo and perfused liver caffeine kinetics in the rat. AB - The kinetics of caffeine (1,3,7-TMX) was investigated in male rats given four different doses (1, 2.5, 10 and 25 mg/kg), comparing the patterns found in vivo and after liver perfusion. The same animals were used in both experimental conditions in order to reduce the variability of the caffeine profile. For doses less than 10 mg/kg or mg/L, caffeine blood or perfusate concentrations/time profiles followed first-order kinetics and the elimination rate constant (average 0.013 min-1) and half-life (55 min) were similar for the in vivo and ex vivo conditions. After larger doses (10 and 25 mg/kg or mg/L), kinetics were nonlinear. The area under the blood or medium concentration-time curve increased, but not in proportion to the dose, and modifications of pharmacokinetic parameters were observed, with significant differences for t 1/2 and CL after 10 and 25 mg/kg or mg/L, due to dose-dependent elimination of caffeine at these doses (Km of 8.3 and 7.8 micrograms/ml in vivo and in vitro, respectively). The two different approaches gave close kinetic estimates in vivo and in vitro. Thus, under standardized conditions, the isolated perfused liver technique is a useful tool for studying the kinetics of drugs eliminated by hepatic metabolism. PMID- 2236897 TI - Effects of anticholinergic antiparkinsonian drugs on binding of muscarinic receptor subtypes in rat brain. AB - Anticholinergic antiparkinsonian drugs have been widely used for the treatment of extrapyramidal disorders for a long time although their pharmacological characterization has been unclear. We studied the rank of potency of the effects of anticholinergic antiparkinsonian drugs to binding of 3H-QNB and 3H-PZ and calculated the affinity of each drug to the M1 receptor. All the drugs were potent inhibitors of 3H-QNB and 3H-PZ binding. The order of potency for 3H-QNB being: mazaticol greater than atropine greater than piroheptine greater than trihexyphenidyl greater than biperiden greater than ethopropazine greater than pirenzepine. The order of potency for 3H-PZ being: mazaticol greater than atropine greater than trihexyphenidyl greater than biperiden greater than ethopropazine greater than pirenzepine. Ki ratio indicated that trihexiphenidyl and biperiden bound to the M1 receptors selectively with high affinity and mazaticol would bind to the M2 receptors with higher affinity than atropine. These data suggest that we may be able to consider the pathophysiology of some extrapyramidal disorders based on the therapeutic efficacy of anticholinergic drugs which selectively affect M1 or M2 receptors. PMID- 2236899 TI - Plasma calcitonin levels in patients with cystic fibrosis. AB - Plasma levels of calcitonin were investigated in patients with cystic fibrosis and compared with age- and sex-matched healthy controls. About forty per cent of the cystic fibrosis patients had plasma calcitonin levels that were markedly higher than normal. Elevated levels were found predominantly in female patients. In general, patients with marked pulmonary involvement had high plasma calcitonin levels. Immunoextraction and gel chromatography, carried out on plasma of one of the patients demonstrated monomer-like forms of calcitonin similar to those found in the healthy subjects. PMID- 2236900 TI - Effects of dietary supplementation with n-3 fatty acids on kidney morphology and the fatty acid composition of phospholipids and triglycerides from mice with polycystic kidney disease. AB - The DBA/2FG-pcy strain of mouse has been developed as an animal model for adult polycystic kidney disease and we have determined the effects of feeding an n-3 fatty acid-enriched diet on kidney morphology and the fatty acid compositions of the constituent phospholipid and triglyceride fractions in this strain. Twelve male and female DBA/2FG-pcy mice were fed lab chow or semi-purified diets containing sunflower seed oil (SO) or a n-3 fatty acid-enriched concentrate (MaxEPA) for 60 days. At necropsy, blood and urine samples were taken and the kidneys processed for examination by light microscopy. Gas-liquid chromatography of the fatty acids in the kidney lipids was also performed. Male and female mice fed the MaxEPA-based diet tended to have lower mean kidney weights. Hematocrits, blood urea, and serum creatinine levels were similar among the lab chow-, SO- and MaxEPA-fed groups. All the groups exhibited a moderate hematuria; the incidence of this symptom was lowest in the MaxEPA-fed male animals. Extensive tubular dilatation was apparent in the cortices and medullae from the lab chow-fed animals; these lesions were slightly less severe in the SO-fed group and least severe in kidneys from the MaxEPA-fed animals. By morphometry, the renal area occupied by cysts was also lowest in the male Max-EPA-fed group; females fed the MaxEPA-based diet did not show a marked decrease in the proportion of kidney area occupied by cysts. Fatty acid compositions of the total phospholipid and triglyceride fractions from kidneys of male mice fed the MaxEPA-based diet showed a reciprocal replacement of the n-6 fatty acids with the n-3 fatty acids compared to kidneys from males fed the SO-based diet. PMID- 2236901 TI - Verapamil-induced creatine kinase loss from rat slow and fast muscles. AB - The purpose of this study was to determine the dose-response relationship between verapamil HCl and creatine kinase (CK) release from isolated rat slow (soleus, S) and fast (flexor digitorum profundus, F) skeletal muscles. Total CK activity in F muscle was approximately 2x greater than in S muscle. For both S and F muscles, CK release as a function of verapamil concentration in the incubation medium was linear (r = 0.94); the slope of the line for F muscle was 4.5x that of the S muscle. S and F muscles lost up to 38-44% of their total CK activity during the 2 hr incubation. The CK activity lost to the medium was 100% of the MM isoform. The mechanism of the enzyme release is not known. PMID- 2236902 TI - Chronic carbamazepine treatment and folate-dependent one-carbon metabolism. PMID- 2236903 TI - Dependence of benzo(a)pyrene metabolism on NADPH pool in normal and glucose-6 phosphate dehydrogenase deficient human fibroblasts. AB - Human skin fibroblasts (HSF), from normal donors and donors carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase, grown in vitro in the presence of 0.25-5 microM benzo(a)pyrene (BaP), produced the following organic soluble metabolites: 9,10-diol, 7,8-diol, quinones, 3- and 9-hydroxide and a more polar fraction, and the following water-soluble metabolites: more polar, 3- and 9 hydroxide and 9,10-diol. Single organic- and water-soluble metabolites increased with BaP concentration in both types of HSF, but the ratio normal/variant increased with BaP concentration. NADPH level and NADPH/NADP+ ratio underwent a slight decrease in normal HSF incubated with 2.5 microM BaP, while a greater fall occurred in the deficient HSF at 0.25 and 2.5 microM BaP. NADPH content seems to be rate-limiting for BaP metabolism in the deficient cells. PMID- 2236904 TI - Lovastatin-acetaminophen subchronic toxicity in mice. AB - A subchronic, toxicity study of lovastatin-acetaminophen combination in s/w mice is reported. Oral administration of lovastatin in corn oil 30 mg/kg three times a week and acetaminophen 0.75% w/v in drinking water for 13 weeks resulted in significant increase in SGPT (ALT) in both male and female mice. Histopathology of the liver revealed centrilobular hepatocyte swelling. These results provide evidence of hepatic injury in s/w mice when concomitantly exposed to lovastatin and acetaminophen. PMID- 2236905 TI - The effect of phenobarbital on the impairment of drug metabolism by carrageenan induced inflammation in male rat. AB - Treatment of male rats with phenobarbital markedly stimulated, the activity of the hepatic microsomal monooxygenase system while in rats bearing carrageenan induced inflammation the activity of this system was lowered. When both agents were administered together, the stimulatory effect of phenobarbital and the inhibitory effect of carrageenan-induced inflammation cancelled each other. PMID- 2236906 TI - An outbreak of congenital hydranencephaly and cerebellar hypoplasia among calves in South Kyushu, Japan: a pathological study. AB - An outbreak of congenital hydranencephaly and cerebellar hypoplasia occurred between November 1985 and May 1986 in Miyazaki, South Kyushu, Japan. Seventy three calves had nervous signs of varying severity such as inability to stand, locomotor difficulties, defective vision and difficulty in sucking. At necropsy, 62 calves had macroscopic lesions in the central nervous system: hydranencephaly accompanied by cerebellar hypoplasia in 47; hydranencephaly alone in eight; and dilatation of the lateral ventricle in seven; none had arthrogryposis. Microscopically, all 62 cases involved various degrees of hypoplasia of neural components, such as total or partial thinning of the cerebral or cerebellar laminae. Heterotopia, such as abnormal islands of granule cells or Purkinje cells was also observed. Fourteen of these animals had other lesions such as non purulent encephalitis, focal gliosis, neuronal degeneration, calcification or pseudocalcification, and cholesterol deposits, activation of vascular endothelial cells and haemorrhage. From the findings, these cases were considered to represent mainly hypoplasia of nerve tissue due to infection with a virus different from Akabane virus. PMID- 2236907 TI - Effect of copper oxide wire particle treatment on establishment of major gastrointestinal nematodes in lambs. AB - Eighty-four 10-week-old lambs were used to investigate the effect of copper oxide wire particle treatment on the establishment of major gastrointestinal nematodes. They were maintained on pasture previously treated to minimise larval contamination. Five grams of uniform sized copper oxide wire particles were given orally five days before infection with either 20,000 Trichostrongylus colubriformis larvae, 20,000 Ostertagia circumcincta larvae or 3000 Haemonchus contortus larvae given as three doses at three-day intervals. The animals were slaughtered 21 or 22 days after the last infective dose. Parasite burdens in the lambs treated with copper oxide wire particles were reduced by 96 per cent in the case of H contortus and by 56 per cent in the case of O circumcincta compared to burdens in controls. There was no significant effect of copper particles on the establishment of T colubriformis. PMID- 2236908 TI - Passive protection of piglets by monoclonal antibodies against experimental infection with Actinobacillus pleuropneumoniae. AB - Mouse monoclonal antibodies 11C11 (an IgG) and 4A9 (an IgM), which combine with a superficial component of cells belonging, respectively, to serovars 1 or 3 of Actinobacillus pleuropneumoniae, were given intraperitoneally 24 hours before and intranasally one hour before two-week-old, colostrum-deprived piglets were exposed by the intranasal route to 10(9) viable cells of either strain Shope 4074 (serovar 1) or 2/10 (serovar 3). Compared with control piglets given phosphate buffered saline or the heterologous monoclonal antibody, this procedure conferred substantial protection against the development of peracute or acute pleuropneumonia. Protection against the experimental disease was somewhat less in other piglets to which monoclonal antibody 4A9 was given only by the intranasal route one hour before the organism was administered than in those given the antibody intraperitoneally 24 hours beforehand, although its effect was still significantly greater than in piglets given phosphate buffered saline only. These two monoclonal antibodies consequently offer means of investigating at the molecular level the pathogenesis of the disease associated with A pleuropneumoniae and the potential value of anti-idiotypes as immunising agents. PMID- 2236909 TI - Anaemia and changes in erythrocyte morphology associated with copper and selenium deficiencies and dietary restriction in rats. AB - Both selenium and copper deficiencies in rats caused morphological changes in erythrocytes but only copper deficiency resulted in anaemia. Similar but less severe morphological changes occurred when rats consuming selenium- and copper adequate diets had their food intake restricted to that of the copper-deficient animals. Since selenium deficiency did not affect the severity of changes due to copper deficiency this suggests that alterations of erythrocyte morphology may not be entirely due to impaired functions of selenium and copper in cell antioxidant systems. Thus, erythrocyte structure was sensitive to several dietary changes and such alterations are probably independent of the anaemia induced by copper deficiency. This possibility should be considered when changes in erythrocyte morphology are attributed to copper or selenium deficiency in animals which also have a restricted food intake. PMID- 2236910 TI - Effect of feeding on plasma secretin concentrations in sheep. AB - Changes in plasma secretin concentration during the 24 hours after feeding were observed in five female sheep fed 1500 g of lucerne pellets and 300 g of orchard grass hay once daily. The pre-feeding concentration of plasma secretin was 50 +/- 9 pg ml-1. The plasma secretin concentration began to increase immediately after the beginning of feeding, reached values approximately double the pre-feeding values six hours after feeding, and remained significantly above the pre-feeding value for more than 10 hours after feeding (P less than 0.01 or less than 0.05). PMID- 2236911 TI - Variation in plasma halflife of gentamicin between species in relation to bodyweight and taxonomy. AB - Data on the plasma halflife of gentamicin during the elimination phase were collected from the literature for 30 species for analysis of the effects of bodyweight and taxonomy. Log halflife was significantly correlated to log bodyweight between species of birds (r = 0.784, n = 9, P less than 0.05) and mammals (r = 0.873, n = 13, P less than 0.001), but not among the poikilotherms (n = 9). The slopes of regressions of log halflife on log bodyweight for mammal and bird species did not differ significantly (0.27 +/- 0.045 and 0.32 +/- 0.095, respectively) but the elevations did (t = 2.73, P less than 0.05). The variations in halflife between species in relation to bodyweight and taxonomy were broadly consistent with variations in glomerular filtration rate. The results illustrate the value of interspecies comparisons of pharmacokinetic data for estimating appropriate dosage regimes for vertebrates for which no specific data are available. PMID- 2236912 TI - Effect of meclofenamic acid on the response of parasite-naive lambs and adult sheep to Ostertagia circumcincta. AB - Meclofenamic acid was used to inhibit prostaglandin synthesis in lambs challenged with Ostertagia circumcincta. It lowered the number of parasites which established in treated animals but not significantly. In treated animals plasma pepsinogen values were elevated at the time of parasite emergence but had dropped below the values achieved in control lambs towards the end of the experiment when parasites were at the adult, lumenal dwelling stage. Meclofenamic acid administered to adult immune ewes during challenge with third stage O circumcincta larvae did not significantly affect the establishment of the parasites, nor did it affect the rise in pepsinogen concentration associated with the challenge. PMID- 2236913 TI - Immunohistochemical demonstration of canine distemper virus antigen as an aid in the diagnosis of canine distemper encephalomyelitis. AB - Brain tissue from 33 dogs with non-suppurative encephalitis was examined for evidence of canine distemper virus (CDV) encephalitis. Sections were examined for lesions, inclusion bodies, syncytial cells and CDV antigen using a double bridge unlabelled antibody enzyme technique. Histopathological lesions considered to be typical of granulomatous meningoencephalomyelitis were found in seven dogs. They all lacked inclusion bodies, syncytial cells and CDV antigen. The remaining 26 dogs all had histopathological lesions typical of CDV encephalitis. Inclusion bodies were found in 24 dogs, four of which also had syncytial cells and CDV antigen was detected immunocytochemically in 25. One dog had no inclusion bodies or syncytial cells and was immunohistochemically negative. Syncytial cells have been found to be of limited diagnostic value for the diagnosis of CDV encephalitis. While inclusion bodies proved to be a good diagnostic criterion for the confirmation of CDV infection, the immunohistochemical demonstration of CDV antigen proved to be superior. CDV antigen was more prevalent than inclusion bodies in tissue sections and much more easily detectable. PMID- 2236914 TI - Ultrastructural abnormalities in seven-day-old broilers reared at high altitude. AB - Fine structural abnormalities in seven-day-old broilers reared at high altitude are described. Tissue changes were seen in the heart, kidney and lung that resembled those previously reported in four-week-old broilers reared at altitude with an ascitic syndrome. Almost half of the hearts examined had myofibril disorganisation and mitochondrial hyperplasia. Renal changes occurred principally in tubule morphology and the lungs showed capillary congestion as well as engorged parabronchi. Increased levels of cartilaginous and osseous nodules in the lungs of 28-day-old ascitic birds reared at high altitude supported observations from a previous study conducted at low altitude. The observations in this study of seven-day-old chicks, may indicate that the embryo is at greater risk of developing abnormalities following exposure to low oxygen tension. PMID- 2236915 TI - Benzylpenicillin kinetics in the ewe: influence of pregnancy and lactation. AB - Benzylpenicillin kinetics were investigated in a breed of sheep adapted to life in barren areas. Important pharmacokinetic differences, dependent on reproductive status (control, pregnancy, lactation), were demonstrated. In control ewes, the steady state volume of distribution was 0.23 +/- 0.15 litre kg-1 and the plasma clearance was 12.4 +/- 3.19 ml kg-1 min-1. During pregnancy, these two parameters were not significantly modified. During lactation, the plasma clearance and volume of distribution were significantly higher than during the control period and pregnancy (27.4 +/- 3.22 ml kg-1 min-1 and 0.696 +/- 0.20 litre kg-1, respectively (P less than 0.01). In contrast the mean residence time (25.0 +/- 4.6 minutes) was similar to those of the control period (17.54 +/- 6.25 minutes) and pregnancy (23.18 +/- 5.94 minutes). These modifications in benzylpenicillin kinetics were explained in terms of fluid balance adjustments and renal function adaptation observed during pregnancy and lactation, and it is suggested that an appropriate dosage regimen for benzylpenicillin should take into account the physiological status of the animal. PMID- 2236916 TI - Species differentiation of Leptospira interrogans serovar hardjo strain Hardjobovis from strain Hardjoprajitno by DNA slot blot hybridisation. AB - Slot blot hybridisation studies with total genomic DNA probes were used to compare Leptospira interrogans serovar hardjo strain Hardjoprajitno, strain Hardjobovis and a number of other Leptospira interrogans serovars. Strains Hardjoprajitno and Hardjobovis were found to have little genetic relationship with each other when compared to some of the other serovars tested. Hardjoprajitno is closely related to serovar icterohaemorrhagiae and not to Hardjobovis whereas Hardjobovis is closely related to serovars vietnam, balcanica and javanica but not to serovar icterohaemorrhagiae; this places strain Hardjoprajitno in the species L interrogans and strain Hardjobovis in the species L borgpetersoni. Because of this lack of genetic relatedness between strains Hardjoprajitno and Hardjobovis, it is proposed to remove the prefix Hardjo from the strain name Hardjobovis and call it L borgpetersoni serovar hardjo strain Bovis. PMID- 2236917 TI - A larval development test for the detection of anthelmintic resistance in nematodes of sheep. AB - First stage larvae of a number of species of parasitic nematodes of sheep have been shown to develop to third stage larvae in the presence of a defined medium consisting of Earle's balanced salt solution and yeast extract. A larval development test, based on this culture technique, was used as a screen for detecting the presence of anthelmintic resistance in nematodes of sheep. It was found to be sensitive and simple to use and also appeared capable of detecting resistance to any of the main anthelmintic groups. Available anthelmintic sensitive and resistant strains of Haemonchus contortus and Ostertagia circumcincta showed differences in development when incubated in the presence of either thiabendazole, levamisole and ivermectin. These differences were expressed as the minimum inhibitory concentration required to prevent larval development over the incubation period. PMID- 2236918 TI - Treatment of experimental enzootic pneumonia of the pig by norfloxacin or its 6 chloro analogue. AB - The 6-chloro analogue of norfloxacin (compound A) administered continuously in the feed at 400 ppm for 21 days markedly reduced the extent and activity of pneumonic lesions in pigs with pneumonia induced experimentally with an homogenate of pneumonic lung and broth cultures of Mycoplasma hyopneumoniae. Norfloxacin at 100 ppm or compound A at 200 ppm in the feed did not reduce the extent of lung lesions, although half the pigs treated with norfloxacin had lesions which appeared histologically to be healing. M hyopneumoniae was detected either by culture or immunofluorescence in the lungs of 60 per cent of the pigs treated with compound A at 400 ppm compared with all the pigs in the other groups. These results were related to the amount of drug in the lungs and body fluids during therapy. Only compound A at 400 ppm produced concentrations in the lungs and bronchial secretions exceeding the minimum inhibitory concentration against M hyopneumoniae. Mycoplasmacidal concentrations were not reached either in the lungs or bronchial secretions which might account partly for the frequent detection of M hyopneumoniae in the lungs after treatment. Drug resistance did not appear to be responsible for the persistence of M hyopneumoniae in vivo since the M hyopneumoniae isolates from the pigs after therapy were sensitive in vitro to both quinolones. As daily weight gain and feed-conversion efficiency improved in all groups of treated pigs compared with the controls, these effects were probably unrelated to the antimycoplasmal activities of the two quinolones. PMID- 2236919 TI - Transvenous pacemaker leads in the dog: an experimental study. AB - Tined transvenous pacing leads were inserted into nine healthy large-breed dogs as part of an experimental study evaluating an implantable defibrillator. The pacing leads were used to induce ventricular fibrillation on the day of insertion, two and four weeks after insertion and then monthly. Despite daily running exercise on and off a leash, the tined leads remained firmly anchored to the right ventricular apex for the full experimental period of up to 12 months. Apart from mechanical endocarditis of the tricuspid valve, and partial penetration of the ventricular wall in one dog, problems associated with the pacing leads were not encountered. The use of tined leads and careful technique may minimise the likelihood of transvenous lead displacement. PMID- 2236920 TI - Field trials of a food-based vaccine to protect village chickens against Newcastle disease. AB - The food pellet vaccine has been shown to be effective in trials conducted under laboratory and simulated field conditions. The village chickens vaccinated with the food pellet vaccine during the field trial were protected against virulent Newcastle disease virus. The efficacy of the food pellet vaccine in the field was evaluated by challenge trial in which 60 per cent protection was obtained, or by monitoring the incidence of Newcastle disease in vaccinated and unvaccinated birds. There was no report of Newcastle disease outbreaks in the vaccinated birds during the two-year period of the field trial. The ease in administering the food pellet vaccine makes it readily accepted by the farmers. PMID- 2236921 TI - Bile agar migration test: a novel method for testing the viability of Dictyocaulus viviparus larvae in lungworm vaccine. AB - A bile agar migration (BAM) test was used to determine the viability of Dictyocaulus viviparus larvae in lungworm vaccines. Percentage migration values for 10 batches of vaccine varied from 8.8 to 33.2 per cent compared with 99 per cent of unirradiated larvae tested under similar conditions. On the other hand a conventional viability count (CVC), based on subjective assessment of larval shape, gave figures of 95.1 to 98.7 per cent for the 10 vaccine batches. The BAM test may therefore have potential for providing a more discriminatory assessment of vaccine quality than CVC. PMID- 2236922 TI - Effect of creep feeding on the incidence, duration and severity of post-weaning diarrhoea in pigs. AB - The effect of creep feeding on the response of pigs weaned at two or three weeks old to infection with an enteropathogenic strain of Escherichia coli (O149; K91[B], K88 a, c [L]) was studied in two separate experiments. Gastric intubation was adopted to regulate the intake of creep feed during the sucking period. Animals were given the enteropathogenic strain either before weaning or at weaning and the course and outcome of the infection followed bacteriologically and clinically. The response of the animals to the infection varied considerably in accord with recent reports of multiple phenotypes (to K88 +ve organisms) among pigs but consumption of creep feed before weaning did not significantly affect the prevalence, duration or severity of the diarrhoea induced experimentally by the organism. Hence reputed immunological responses mounted against dietary antigens did not predispose to or protect against this infection. PMID- 2236923 TI - Use of the forced oscillating airflow technique to measure the resistance of the equine upper airway: effects of laryngoventriculectomy and laryngoplasty. AB - Investigations were carried out to determine whether measurements of total respiratory resistance (TRR) made in resting animals could detect changes due to laryngeal hemiplegia. Control values of TRR were obtained in eight ponies and in six of these the measurements were repeated after division of the left recurrent laryngeal nerve in the mid-cervical region; two were retained as controls. A further set of measurements were made before two of the operated animals were subjected to left laryngoventriculectomy (Hobday operation). A laryngoplasty ('tie-back' operation) was performed on another two animals. Measurements of TRR were made at three-monthly intervals on all eight ponies for the next two years. Endoscopic examination of the larynx was carried out at the time of the measurements. All ponies showed a marked, but regular, variation in TRR over the two-year observation period. Nerve section was shown to be associated with an increase in TRR in five ponies. The Hobday operation decreased TRR in one animal and had no marked effect in the second. The tie-back operation was associated with a decreased TRR in one pony and an increase in the second. Autopsies were carried out on all six operated ponies and measurements of TRR and lower respiratory resistance (LRR) were made immediately before the animals were killed. Evidence of regeneration of the recurrent laryngeal nerve was seen in one of the ponies which underwent the Hobday operation. Histological evidence of regeneration was found in another pony.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236924 TI - Inclusion of low metabolisable energy wheat in broiler diets and the incidence of the fatty liver and kidney syndrome. AB - Chickens were fed a diet containing wheat of low metabolisable energy (ME) content (11.3 MJ kg-1 dry matter [DM]) or a diet containing a wheat of high-ME content (14.5 MJ kg-1 DM). The diets, although of identical ingredient composition differed in energy to protein ratio. Chicks fed the diet containing the low-ME wheat and with the low ratio had more severe biotin deficiency lesions but a much reduced incidence of the fatty liver and kidney syndrome. PMID- 2236925 TI - Isolation and identification of anaerobic bacteria from ovine foot rot in Spain. AB - A microbiological study was made of 125 Merino sheep showing clinical signs of foot rot. A total of 435 strictly anaerobic strains were isolated, belonging to the following genera: Bacteroides, Peptostreptococcus, Tissierella, Fusobacterium, Megasphaera, Eubacterium, Acidaminococcus, Clostridium, Peptococcus and Propionibacterium. Of the 35 species obtained, the following were found in more than 10 per cent of animals sampled: Bacteroides nodosus, B putredinis, B buccae, B ruminicola subspecies brevis, Tissierella praeacuta, Peptostreptococcus anaerobius and Megasphaera elsdenii. Six culture media were used for isolation. Agar brucella and agar brucella enriched with G-N anaerobe supplement proved to be the most efficient for isolating anaerobic bacteria. PMID- 2236926 TI - A new type of macrolide resistance in staphylococci from bovine subclinical mastitis. AB - Staphylococcal (nine Staphylococcus aureus and 14 coagulase negative) strains, isolated from subclinical bovine mastitis, showed three patterns of macrolide resistance: (i) macrolide-lincosamide constitutive resistance; (ii) macrolide generalised resistance; and (iii) lincosamide generalised resistance. The second pattern of resistance appeared to be a new resistance phenomenon. None of the strains showed dissociated or inducible resistance, neither was there any strain which could inactivate erythromycin, oleandomycin, lincomycin or clindamycin. PMID- 2236927 TI - Elemental composition, water, and total lipid content in peripheral nerves, spinal cord and brain of healthy adult dogs. AB - Peripheral nerves, spinal cord, and brain of healthy adult dogs were analysed biochemically for sodium, potassium, calcium, magnesium, copper, zinc, iron, aluminium, silicon, total chloride, total tissue water and total lipid content. Flame atomic absorption spectrophotometry was used for elemental quantitation of the hydrochloric acid tissue extracts. Cerebrum and spinal cord had similar values for all parameters measured. Total sodium values were higher in nerves compared to central nervous system (CNS) (brain and spinal cord), while respective values for potassium were lower. Tissue levels of calcium, iron and silicon were comparable in brain, spinal cord and nerves. However, magnesium concentrations were two to three times higher in CNS than in nerves; and the reverse was true for aluminium levels. Tissue concentrations of zinc and copper were marginally higher in CNS than in nerves. PMID- 2236928 TI - Effects of dietary borate and aluminate on riboflavin metabolism in the breeding hen. AB - Breeding hens were used to investigate the effects of aluminate and borate ingestion on riboflavin metabolism. Groups of six hens were fed on either a control diet, or the control diet plus 15 g kg-1 of either sodium metaborate or sodium meta-aluminate. All diets contained 6 mg kg-1 riboflavin. Daily egg production per hen in the borate group had mean values of 0.71, 0.21 and 0.02 for the three weeks of the study. The values were 0.91, 0.91, 0.86 and 0.86, 0.74, 0.89 for the control and aluminate groups, respectively. Fertility (fertile eggs per 100 set) and hatchability (live chicks per 100 fertile eggs) were both nil in the borate-treated hens, compared with 57 and 95 and 59 and 100 for the control and aluminate-treated hens, respectively. Fluorimetric analysis of blood plasma, egg yolk and albumen showed that the riboflavin contents of all tissues were greatly reduced in the borate-treated hens. Borate ingestion can therefore induce a severe riboflavin deficiency in the hen, but aluminium, a more universal contaminant of food or water, did not impair riboflavin metabolism when fed as aluminate. PMID- 2236929 TI - Dose-related effect of beclomethasone dipropionate on airway responsiveness in asthma. AB - The effects of twice daily inhaled beclomethasone dipropionate (BDP) at two dose levels (500 and 1,000 micrograms daily) on the airway responsiveness to inhaled histamine was evaluated by a randomized, single-blind, cross-over study in 10 patients with stable asthma. The 12-week study began with a 3-week run-in period of baseline treatment, which was continued unchanged throughout the study, and the two treatment periods were separated by a 3-week placebo period. Patients attended the laboratory every 3 weeks for spirometry and histamine inhalation tests to determine the provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 s (PC20 of FEV1). There was a similar significant improvement (p less than 0.05) in mean FEV1 after both treatments. There was no significant change in PC20 after treatment with 500 micrograms daily, the geometric mean being 0.587 mg/ml after the placebo period and 0.860 mg/ml after BDP treatment. There was a significant improvement in PC20 (1.930 mg/ml) after treatment with 1,000 micrograms BDP daily in comparison with the placebo and treatment periods with 500 micrograms BDP daily (p less than 0.001). These results suggest that higher doses than usual of inhaled BDP must be used to control airway responsiveness in asthmatics. PMID- 2236930 TI - The state of leukocyte adhesiveness/aggregation in the peripheral blood of patients with respiratory tract infections. AB - The state of leukocyte adhesiveness/aggregation (LAA) in the peripheral blood has been employed as a marker of inflammation. In the present study we examined patients with varying intensities of inflammation caused by respiratory tract infections to further investigate the reliability of the state of LAA for the detection and assessment of the severity of disease activity. The study includes 140 controls, 46 patients with upper respiratory tract infection, 30 with bronchitis, 27 with suspicion of pulmonary infiltrate, and 39 with small and 18 with large pulmonary infiltrate. Assessment was based on assuming an increasing severity of inflammation from the 1st to the 6th diagnostic category and by making use of discriminant analysis. It was found that the state of LAA proved to be the best variable to classify the patients into their diagnostic category (F to enter 27), followed by erythrocyte sedimentation rate at the 1st h (F to enter 20.8) and total white blood cell count (F to enter 8.3). These studies were followed by animal experimentation. A highly significant correlation (p = 0.005) was found between the state of LAA in the peripheral blood and the degree of pulmonary leukostasis in a model of endotoxemia in rabbits. These results suggest that the state of LAA is not an epiphenomenon and represents the tendency of the white blood cells to stick to the endothelium which facilitates their migration into the tissues. PMID- 2236931 TI - Severe acute asthma. Pathophysiology, clinical assessment, and treatment. AB - Bronchial asthma is characterized as a disease with recurrent, reversible, and generalized airway obstruction and an increased airway responsiveness to nonspecific stimuli. Besides symptoms of airway hyperresponsiveness, episodic asthmatic attacks, and chronic airway obstruction, severe acute asthma, or 'status asthmaticus', is an important and life-threatening manifestation of the disease. This paper gives an overview of the pathophysiology, clinical risk assessment, and treatment of severe acute asthma. PMID- 2236932 TI - Serial physiologic studies of a chronic obstructive pulmonary disease patient in acute respiratory failure: clues for weaning? AB - A patient with severe chronic obstructive pulmonary disease was studied during acute respiratory failure. On the day of intubation his respiratory rate was 42, the tidal volume 295 ml, and the maximal inspiratory pressure 8 cm H2O. These parameters improved with rest by mechanical ventilation to 16, 620 ml, and 30 cm H2O, respectively, on the day of successful weaning. Daily tidal volumes correlated significantly with maximal inspiratory muscle pressures (r = 0.936; p less than 0.001). Respiratory system compliances and resistances were measured by the inflation, the end-inspiratory occlusion, and the interrupter methods. In general, inflation compliance and occlusion compliance were comparable and significantly smaller than the interrupter compliance (p less than 0.002 and p less than 0.003, respectively), whereas inflation resistance and occlusion maximal resistance were also comparable but significantly smaller than the interrupter resistance (p less than 0.0008 and p less than 0.0006, respectively). The former was due to increased hysteresis of the pressure volume curves and the latter due to expiratory compression of airways. The compliance was low, and the resistance was high on the day of intubation and became much higher and lower, respectively, on the day of successful extubation. These physiological changes were associated with weaning difficulty. We conclude that respiratory failure and weaning are complex physiologic events under the influence of muscle strength, lung mechanics, gas exchange, and control of breathing. Therefore, prediction of weaning success based upon one or two measured parameters as has been done is probably inadequate in difficult patients. PMID- 2236933 TI - Primary pulmonary manifestation of Hodgkin's disease. AB - We describe 2 patients with rare primary pulmonary manifestation of Hodgkin's disease. Our 1st patient, who had unilateral pulmonary involvement and has been treated with segmental resection and cyclophosphamide, has survived greater than 18 years without relapse. He is the first patient reported with such a long survival. Our 2nd patient had bilateral pulmonary involvement and B symptoms and has been treated with an aggressive chemotherapy regimen. She is alive after 3 years without evidence of disease. PMID- 2236935 TI - Intrathoracic lipomas demonstrated by computed tomography. AB - Nine cases of intrathoracic lipoma are reported. Computed tomography (CT) proved to be helpful in the diagnosis and management of these cases. The attenuations of the masses ranged from -70 to -140 Hounsfield units (HU). In 4 cases, needle biopsies were taken, confirming lipoma with mature fat cells. One patient also had a coelomic cyst with an attenuation of 20 HU, which was confirmed at thoracotomy. Another had an atypical lipoma which infiltrated the thoracic wall but was benign. In conclusion, we recommended investigation with CT scan for the diagnosis of lipoma. PMID- 2236934 TI - Cardiopulmonary effects of a brief exposure to cigarette smoke in the guinea pig. AB - To investigate whether the acute inflammatory response produced by acute cigarette smoke exposure is associated with alterations in pulmonary and cardiovascular function, using a respirator we exposed 8 guinea pigs to 350 ml of cigarette smoke diluted in 2,000 ml room air for 10 min. Lung volumes, pressure volume curves and flow volume curves were performed. Measurements of pulmonary artery pressure, systemic pressure, heart rate and cardiac output were taken at baseline, immediately after the smoke exposure, and 1.5 h after smoke exposure. Aliquots of peripheral blood for total white cell count and differential count were obtained. After animal sacrifice, the right lung was lavaged and white cell count and differential count performed. We found that acute exposure to cigarette smoke produced a peripheral blood neutrophilia which rose progressively from a baseline of 36.3 +/- 8% to a maximum of 72.2 +/- 7.7% at 1.5 h after exposure. There was pulmonary neutrophilia with 24.6 +/- 6.3% neutrophils in the lavage fluid of the smoke-exposed animals compared to 8.4 +/- 4.3% in the control animals. Immediately after smoke exposure, there was acute airflow obstruction with a decrease in the peak flow and forced expiratory flow between 25-75% vital capacity. This was associated with airtrapping, as shown by a transient increase in residual volume. There was a slight decrease in systemic blood pressure in the smoke-exposed animals associated with a nonsignificant decrease in the heart rate, and the cardiac output remained stable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236936 TI - Relationship between nonspecific airway hyperreactivity and antigen-induced contraction in an allergic animal model in vitro. AB - Tracheal strips from actively sensitized guinea pigs exhibited an enhanced responsiveness (greater maximal effects; Emax) and sensitivity (smaller effective concentration 50%; pD2) to CaCl2 (in K(+)-depolarized tissues), KCl and histamine compared with that of strips from nonsensitized animals. A significant correlation was found between the magnitude of the contraction produced by bovine serum albumin (1 mg/ml) and the Emax and pD2 values of CaCl2, KCl and histamine in tracheal strips from sensitized guinea pigs. This indicates that specific and nonspecific challenges correlate in sensitized guinea pig trachea. PMID- 2236937 TI - Vagal cooling and positive end-expiratory pressure reduce systemic to pulmonary bronchial blood flow in dogs. AB - Positive end-expiratory pressure (PEEP) reduces systemic to pulmonary bronchial blood flow [Qbr(s-p)] presumably because it increases bronchial vascular resistance. Since PEEP increases lung volume and thus could stimulate pulmonary stretch receptors, we investigated the hypothesis that the PEEP-related decrease in bronchial blood flow was due to a reflex mediated by the vagus. In open-chest dogs the left lower lobe (LLL) was isolated, independently ventilated, perfused in situ with a closed pulmonary vascular circuit and weighed continuously. Qbr(s p) was measured as LLL vascular circuit overflow and changes in LLL weight. When LLL PEEP was increased from 5 to 15 cm H2O in a group of 11 dogs Qbr(s-p) was reduced by half from 60.8 +/- 10.5 to 31.6 +/- 6.1 ml/min/100 g dry lobe weight. In another group of 7 dogs Qbr(s-p) was 46.5 +/- 6.9 with PEEP = 5 cm H2O; it decreased to 28.3 +/- 6.8 with bilateral cervical vagal cooling (0-1.5 degrees C) and did not decrease further after increasing PEEP to 15 cm H2O. We conclude that the effect of resting vagal tone is to increase Qbr(s-p) and that the effect of PEEP on Qbr(s-p) may be mediated at least partially by vagal influences. PMID- 2236938 TI - Prophylactic treatment to the fellow eye of patients with phakic lattice retinal detachment: analysis of failures and risks of treatment. AB - The authors performed a retrospective analysis on 296 phakic patients who had bilateral lattice degeneration and a retinal detachment in one eye. The analysis was done to determine the complications of full prophylactic treatment to lattice and breaks in the fellow eye and to explain the reasons that this treatment sometimes did not prevent new retinal breaks or detachments. The patients were followed for a mean +/- SD of 7.415 +/- 5.422 years after their first detachment. Twenty-four new tears occurred in the fellow eyes during this time, seven (29.2%) of which were away from areas of visible lattice. Prophylactic treatment did not appear to cause new tears or increase the risk of detachment if a new tear occurred. It also did not compromise the surgical repair in those patients who had eyes in which new breaks or detachments developed. The risk of visual loss was similar in those patients receiving prophylactic treatment compared with those not receiving treatment. PMID- 2236939 TI - Complications of primary scleral buckling procedures in high myopia. AB - Repair of retinal detachments in high myopia may be associated with numerous intraoperative complications. Included are complications involved with the drainage of subretinal fluid as well as those arising from thin sclera. Highly myopic eyes tend to be more prone to these complications than less myopic or nonmyopic eyes. A retrospective study of 51 consecutive highly myopic eyes (six diopters (D) or greater) undergoing primary scleral buckling procedures was performed. Intraoperative complications occurred in a total of six eyes (12%). The complications were related to drainage of subretinal fluid in four eyes (8%) and associated with thin sclera in two eyes (4%). Despite the above-noted complications, there was no adverse effect on the final level of visual acuity or on the anatomic status of the retina. In the comparison of the incidence of drainage-related complications with previously published studies not preselected according to refractive status, there appears to be no added risk of complications based on the degree of myopia. PMID- 2236940 TI - Vitrectomy in asteroid hyalosis. AB - Asteroid hyalosis (AH), a condition in which calcium-lipid complexes form in the collagen meshwork of the vitreous, affects from 0.5% to 0.9% of the general population. In patients with dense AH and visual loss, obscuration of fundus detail on ophthalmoscopy and even on fluorescein angiography may complicate the diagnosis and treatment of underlying posterior segment disease. To evaluate the usefulness of vitrectomy in AH, we reviewed 7 cases of dense AH in 6 patients who underwent vitrectomy in the setting of decreased visual acuity of uncertain cause. Additional diagnoses made following surgery included age-related macular degeneration (ARMD) in 2 eyes, ARMD with associated epiretinal membrane in one eye, and the staging of diabetic retinopathy as proliferative in one eye. Although no major surgical complications occurred in this series, the potential for serious complications exists, and pars plana vitrectomy (PPV) should be considered only after less invasive diagnostic evaluations and therapeutic approaches have been exhausted. PMID- 2236942 TI - Central venous stasis retinopathy following the use of tranexamic acid. AB - Central venous stasis retinopathy (CVSR) was observed in two young women following the administration of oral tranexamic acid (TA) for the treatment of menorrhagia. Clinical and laboratory parameters were normal. Withdrawal of the drug and treatment with systemic steroids and fibrinolytic drugs resulted in improvement of visual acuity to 6/6. The pathogenesis of the CVSR in these cases is suggested, and the rationale of systemic treatment is discussed. PMID- 2236941 TI - Goldmann-Favre maculopathy. AB - A healthy 17-year-old girl presented with typical symptoms and physical features of Goldmann-Favre vitreoretinal degeneration. She had reduced visual acuity in both eyes and night blindness. Her parents were first cousins. Striking fundus features included typical maculopathy with a radiating stellate pattern surrounded by tiny vacuole-like pockets of retinoschisis throughout the posterior pole within the temporal vascular arcades. The fundus features were quite typical and permitted a firm diagnosis when combined with the other features of night blindness, gender, and electroretinogram (ERG) abnormalities. PMID- 2236943 TI - Bilateral macular holes in sporadic posterior microphthalmos. AB - The authors report an unusual sporadic case of bilateral posterior microphthalmos in an 8-year-old Chinese girl. Cycloplegic refraction showed hyperopia of 12.5 diopters in both eyes. Anterior segment examination showed normal corneal diameters, open angles, and normal lens thicknesses. Ultrasonography showed short vitreous compartments resulting in short axial lengths of 17.2 mm. Fundoscopy showed full-thickness macular holes associated with radiate retinal striae. This is the first report of bilateral macular hole formation in sporadic posterior microphthalmos. The literature is reviewed. PMID- 2236944 TI - The histopathology of successful retinal reattachment. AB - Fifteen eyes with rhegmatogenous retinal detachment that were successfully reattached with scleral buckling were studied histopathologically after enucleation or autopsy. Postoperative visual acuities ranged from 20/25 to 5/200. Epiretinal membranes were present in 9 of 15 eyes (60%) and cystoid macular edema was present in 4 of 15 (26%). Although the reattached retina was of normal morphology by light microscopy in 9 of 15 eyes, significant atrophy of outer retinal layers was noted in 4 of 15 eyes (26%). In 5 of 13 patients, reduced postoperative vision could be histopathologically correlated with macular edema or lack of retinal regeneration, but there was no compelling histopathologic explanation for reduced vision noted in 5 other cases. PMID- 2236945 TI - Surgical treatment of postoperative dilated, nonreactive pupil in eyes after combined pars plana lensectomy and vitrectomy. AB - Synechiae between the iris and tissue posterior to the iris can cause a markedly dilated, nonreactive pupil that is cosmetically undesirable after combined pars plana lensectomy and vitrectomy for complicated forms of retinal detachment. The authors have used a combined limbal and pars plana approach to lyse the posterior synechiae, resulting in partial pupillary constriction. The surgical technique is described, and clinical results are illustrated. PMID- 2236946 TI - A technique for the transfer of retinal images from the mirror of a contact lens. AB - In 1965 Rene Dufour developed a method for the direct transfer of retinal images reflected in the mirrors of a contact lens to retinal drawing paper. The retinal images are drawn on the reverse side of semi-transparent paper that is oriented such that the sector of the retinal diagram is aligned with the mirror of the contact lens that is viewing the sector. The images can be drawn exactly as they are seen in the mirror. When the drawing is viewed right-side-up over a light box, the detail is oriented correctly. The method is valuable for the precise localization of retinal breaks that are discovered through the slit-lamp microscope but are too small to be seen by indirect ophthalmoscopy. The breaks can be oriented in relation to other fundus detail large enough to be seen through the ophthalmoscope and then found at the operating table without the aid of a microscope. PMID- 2236947 TI - Clinicopathologic correlation of recurrent epiretinal membranes after previous surgical removal. AB - Recurrent epiretinal membranes (ERMs) causing macular pucker developed after surgical removal in seven eyes and were subsequently removed. A specimen was available for electron microscopic study from four of the seven primary operations and all seven of the repeat operations. The diagnostic associations for the primary cases included retinal holes or tears (four eyes), trauma, inflammation (one eye each). In one eye the membrane was idiopathic. The primary and recurrent ERM specimens contained similar cell types and structural characteristics but were not identical. No one cell type predominated in either primary or recurrent ERM. Compared with studies of idiopathic ERMs, myofibroblasts were present with increased frequency in recurrent membranes. Fibrocytes, fibrous astrocytes, and retinal pigment epithelial cells were also present in most specimens. Other features of both the primary and recurrent ERM specimens included the presence of cells with myoblastic differentiation, fragments of internal limiting membrane, new collagen, and nerve fiber elements. PMID- 2236948 TI - Syphilitic disc edema and periphlebitis. AB - This photo essay shows the retinal findings in a patient with presumed syphilitic disc edema and periphlebitis. Resolution of these findings after treatment with penicillin is documented by improvement in visual acuity from 20/50 to 20/25 in the right eye and from 20/200 to 2/20 in the left eye. Photographic documentation of the resolution of retinal findings, including disc edema and periphlebitis, is presented. PMID- 2236949 TI - Penetrating ocular injuries. PMID- 2236950 TI - Retinol macroaneurysms treated with the yellow dye laser. PMID- 2236951 TI - [Newer modes of mechanical ventilation]. PMID- 2236952 TI - [High frequency chest wall compression ventilation]. PMID- 2236953 TI - [Respiratory muscle fatigue and artificial ventilation: reduced respiratory work by ventilatory support and unloaded muscle atrophy]. PMID- 2236954 TI - [Computer-controlled optimization of ventilatory support]. PMID- 2236955 TI - [Home ventilation therapy]. PMID- 2236956 TI - [An application of ambulatory intracardiac electrogram recording by telemetry system on analysis of pacemaker function]. PMID- 2236957 TI - [Coronary angioscopy system with PTCA balloon catheter]. PMID- 2236958 TI - [Atrioventricular delay and diastolic mitral regurgitation in patient with DDD pacemaker implantation, and cardiac function]. AB - We examined the mitral valve motion, the mitral valve flow pattern, and changing atrioventricular (AV) delay in 34 patients with DDD pacemaker implantation, using M-mode echocardiography and pulse Doppler echocardiography. In 28 patients, B-B' step and diastolic mitral regurgitation (DMR) were induced by extending the AV delay. 8 of 12 patients who showed B-B' step and DMR with the AV delay less than or equal to 165 mS had heart failures. In such patients, P-B-B' step (DMR) interval was 174 +/- 31 mS shorter than the other patients (216 +/- 26 mS, p less than 0.001), and Q-C interval was 131 +/- 26 mS longer than the other patients (63 +/- 31 mS, p less than 0.001). The minimal value of the AV delay that induces B-B' step and DMR can be decided under the influence of cardiac functions, and this echocardiographic examination is useful, giving us information about the cardiac function of the patients with DDD-PM. B-B' step is the mitral valve motion that corresponds with the DMR, so we can check the DMR through the B-B' step easily. PMID- 2236960 TI - [Distinctive response of coronary artery compared acute myocardial infarction with angina pectoris associated with angioplasty]. AB - There has been much controversy over the mechanism of successful percutaneous transluminal coronary angioplasty (PTCA). To examine clinical and angiographic factors that might be related to a successful PTCA, we assessed 224 branches treated with emergent or elective angioplasty in evolving acute myocardial infarction (AMI) and angina pectoris (AP). The patients were divided into three groups; group 1 (G1): AP (n = 113), group 2 (G2): AMI with complete obstruction of infarct-related artery (IRA) (n = 79), group 3 (G3): AMI with incomplete obstruction of IRA (n = 32). The morphology of stenotic lesion was classified into smooth type and irregular type. The former shows concentric smooth border, the latter shows eccentric irregular border and multiple irregular border according to the Ambrose classification. Regarding the severity of the stenosis immediately after successful PTCA, there was no significant differences between G2 and G3, however in G1 it was significantly higher than in other groups (G1 vs G2 vs G3, 56% vs 81% vs 78%, p less than 0.001). Irregular type at stenotic lesions before PTCA were present in 72 of 113 branches in G1 vs 60 of 69 in G2 and G3. Regarding the incidence of acute coronary obstruction during PTCA, there was no significant differences between G1 and G2. However, in G3 it was significantly higher than in other groups (G1 vs G2 vs G3, 8% vs 9% vs 38%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236959 TI - [Contractile properties of coronary artery bypass conduit--comparison between saphenous vein and internal mammary artery]. AB - This study was designed to examine the response of coronary artery bypass conduit to serotonin, phenylephrine, and ergonovine as provocation agents of vasoconstriction. Saphenous veins (SV) and internal mammary arteries (IMA) were obtained during coronary artery bypass grafting (CABG), and their contractile properties were measured using isometric contraction recording apparatus. Both SV and IMA showed sigmoid contraction curves indicating dose dependence to ergonovine, serotonin, and phenylephrine. The concentration-response relations for phenylephrine showed a similar curve in both SV and IMA, however, those for ergonovine and serotonin showed a leftward shift in SV compared with IMA. Half maximum effective dose for ergonovine and serotonin were less in SV than IMA. From these results, it was suggested that "perioperative spasm" during CABG might occur not only in coronary arteries but also in the graft conduit itself. Graft spasm might be a possible mechanism for occlusion of the bypass graft. In conclusion, greater hyperreactivity of SV compared with IMA in response to ergonovine and serotonin was suggested, so it is concluded that, from this point of view, IMA is more suitable for use in CABG. PMID- 2236961 TI - [Silent myocardial ischemia in diabetics--by treadmill exercise testing]. AB - We examined silent myocardial ischemia in diabetics by treadmill exercise testing. There were 28 diabetic men and 64 diabetic woman without angina, with a mean age of 59 +/- 11 years. Symptom-limited treadmill exercise testing was performed, and we used the electrocardiogram during exercise and immediately after exercise for judgement. ST segment depression was defined as positive if there was at least 0.1 mV of ST depression 80 ms from the J point. It was defined as negative if max heart rate (HR) was more than 80% of target HR and there was no significant ST depression. It was defined as equivocal if there was no significant ST depression but max HR was less than 80% of target HR. In 92 diabetics, 21 patients (23%) showed positive ST depression, 35 (38%) showed negative ST depression, 36 (39%) showed equivocal ST depression. In 56 diabetics exclusive of treadmill equivocal patients, 38% of patients showed positive ST depression. Treadmill positive diabetics had a significantly higher rate of smokers, patients with hypertension, and a higher triglyceride level as compared with treadmill negative diabetics. Coronary arteriography, which was performed in six treadmill positive diabetics, revealed coronary stenosis of more than 75% in four patients. PMID- 2236962 TI - [Biphasic effects of a combined administration of SOD and CAT on Ca overload and recovery of function and metabolites]. AB - The present study was performed to clarify whether the combination of superoxide dismutase (SOD) and catalase (CAT) can reduce Ca2+ overload and improve recovery of function and metabolites during reperfusion in isolated globally ischemic rat hearts. In non-treated hearts, left ventricular developed pressure (LVDP) recovered to only 30% of the preischemic value with elevation of left ventricular end-diastolic pressure (LVEDP) after 30 min of reperfusion following 30 min of global zero-flow ischemia. ATP and CP fell by 40% and 60%, respectively with 13 fold increase in Ca2+ uptake. A combined administration of SOD and CAT at low concentrations improved recovery of function (LVDP to 60%), reduced Ca2+ uptake (10 fold) without any improvement in high energy phosphates. However a combination of SOD and CAT at higher concentrations did not improve, or even deteriorate functional and metabolic recovery with increased Ca2+ overload (12 to 14 fold). These results indicated that the extracellular free radical scavengers, SOD and CAT, had a biphasic effect on reperfusion injury and could be partially beneficial at low concentrations. PMID- 2236963 TI - [A case of acute pericarditis secondary to mediastinitis]. AB - A 45-year-old man who complained of swallowing disturbance and chest pain in inspiration phase was admitted for evaluation of "pericarditis". A chest X-ray film on admission disclosed a wide mediastinal shadow and pleural effusion on the right side. Bilateral tonsils were swollen, and covered with pus. A Computed tomogram of the chest showed a shadow of exudate contained with air in the mediastinum. Mediastinal drainage, tonsillectomy and drainage of fistula from pre tracheal space to upper mediastinum were immediately performed. Staphylococcus aureus was confirmed from the sputum and mediastinal effusion. Thus, acute mediastinitis was confirmed as an etiological diagnosis of "pericarditis" in this patient. PMID- 2236964 TI - [A successfully operated case of tetralogy of Fallot with marked left ventricular dysfunction in adult]. AB - Adults, especially high-aged patients with tetralogy of Fallot (TOF) are said to have a higher operative risk than younger ones because of fragility of their myocardium, bleeding from rich collateral circulation to lungs, and other complications such as brain abscess and endocarditis. It is often difficult to determine the surgical risk for total correction in cases of high-aged patients who have such complications. We report a successfully operated high-aged case of TOF with marked left ventricular dysfunction. A 52-year-old male was referred to our hospital because of exertional dyspnea and cyanosis. He had a history of cerebral embolism and meningitis several months prior to admission. On admission, he was NYHA class 3, and cyanosis and clubbed fingers were present. Cardiac catheterization showed a large VSD, 50% over-riding of the aorta and an infundibular pulmonary stenosis. Right to left shunt was 60% and Qp/Qs was 0.38. The left ventricular end diastolic volume index was 109 ml/m2, slightly larger than normal, and the ejection fraction was only 30%. This left ventricular dysfunction was thought to be caused by fibrosis of the myocardium due to longstanding hypoxemia and hypoxemia itself. There is no previous case report dealing with a successful total correction for a high-aged patient with TOF associated with such a severe left ventricular dysfunction. Congestive heart failure in the post-operative period was successfully treated by catecholamine for two weeks. Postoperative cardiac catheterization showed a small left-to-right shunt, and an improvement of left ventricular ejection fraction from 30% to 38%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2236965 TI - [A case of hypertrophic cardiomyopathy with right ventricular outflow obstruction manifested during three-year follow-up study]. AB - A case is reported of a 55-year-old female with idiopathic hypertrophic cardiomyopathy, which was accompanied with outflow obstruction in the right ventricle developed during the previous 3 years without lesion of the left ventricle. In 1984, she was admitted to our hospital to be examined for cardiac murmurs and abnormal electrocardiogram including ST depression and inverted T. The findings of echocardiography and cardiac catheterization revealed non obstructive hypertrophic cardiomyopathy. She had been treated with sympathetic beta-blockade and calcium antagonist for 3 years until she complained of dyspnea on exertion, and she was readmitted to our hospital in 1987. Echocardiographic findings showed protrusion of the ventricular septum toward the right ventricle and systolic turbulent flow along the right ventricular outflow tract (by pulsed Doppler technique). A pressure gradient of 20 mmHg across the protrusion was detected by the examination of the cardiac catheter. However, neither protrusion nor pressure gradient was observed in the left ventricular outflow tract as well as that in 1984. Idiopathic hypertrophic cardiomyopathy has been described as involving both ventricles, and outflow obstruction is the usual hemodynamic finding in the left ventricle. However, right ventricular outflow obstruction is the usual hemodynamic finding in the left ventricle. However, right ventricular outflow obstruction with the left ventricular outflow tract intact has been very rare. In addition, in this case, the change of hemodynamic characteristics from non-obstructive to obstructive hypertrophic cardiomyopathy, and the development of these changes only in the right ventricle were observed during the last 3 years. PMID- 2236966 TI - [Inhibition of vasospastic angina by alcohol ingestion]. AB - A 66-year-old man having a long history of angina on effort has started to show frequent episodes of angina at rest since 6 months ago. He noticed that chest pain was uncommon after taking alcohol. A variant form of angina pectoris (variant angina) was diagnosed by documentation of typical ST elevation during anginal attack and also by inducing coronary arterial spasm with intracoronary administration of ergonovine maleate. Ambulatory ECG monitoring revealed frequent ST elevation during sleep. Since the history suggested that alcohol ingestion could be effective for preventing variant angina, this effect was examined by giving 540 ml of "sake" in the evening. Variant angina was inhibited, while plasma ethanol was detected. The plasma ethanol reached its peak value as 152 mg/dl at 10 o'clock pm and returned to zero after 12 hours. When ethanol disappeared in the plasma, variant angina recurred again. Although the precise mechanism for inhibition of variant angina by alcohol ingestion is not clear, alcohol or its metabolite such as acetaldehyde seems to be able to inhibit coronary arterial spasm. PMID- 2236967 TI - [Coronary revascularization with reduction of serum cholesterol level using LDL apheresis in patient with homozygous familial hypercholesterolemia]. AB - We reported a case of a 48-year-old male with homozygous familial hypercholesterolemia who underwent coronary revascularization successfully. Coronary artery bypass grafting (CABG) utilizing internal mammary artery graft to LAD, and percutaneous transluminal angioplasty for residual stenosis after CABG was able to relieve symptomatic myocardial ischemia. LDL apheresis every two weeks in addition to combined drug treatment had maintained total cholesterol at an acceptable level (120-280 mg/dl) before and after CABG. It was confirmed by repetition of coronary angiography at one year after CABG that all grafts were widely patent, and the native coronary artery did not accelerate the atherosclerotic lesion. It was important in patients with homozygous familial hypercholesterolemia, to carry out active coronary revascularization with reduction of serum cholesterol level by using LDL apheresis. PMID- 2236968 TI - [Right pulmonary artery obstruction and pulmonary hypertension secondary to aortitis syndrome]. AB - A 56-year-old woman with aortic arch syndrome and finally right pulmonary artery obstruction secondary to Takayasu's aortitis was presented. She had had a history of visual disturbance and dizziness when she looked upward since 1983. On admission in July, 1984, aortography showed obstruction of the right innominate artery and of the left subclavian artery. Pulmonary arterial pressure, pulmonary perfusion and ventilation images seemed to be normal at that time. After discharge from our hospital, she began in 1987, to be aware of dyspnea on effort. Because of this symptom, she was admitted again in March, 1988. The pulmonary perfusion images showed complete lack of perfusion in the right lung, and arterial blood gas showed hypoxia with 62 mmHg in PaO2, 39 mmHg in PaCO2. Cardiac catheterization confirmed pulmonary hypertension with pulmonary artery pressure of 56/18 mmHg. In conclusion, pulmonary perfusion and ventilation scintigraphy proved to be the best way to clarify the nature of a lesion of the pulmonary artery in aortitis syndrome. PMID- 2236969 TI - [Prognosis of intrahospital cardiorespiratory arrest. Experience at a referral center for internal medicine and surgery]. AB - In order to identify prognostic features associated with in-hospital cardiopulmonary arrest (CPA) a prospective study was designed. A total of 130 first episodes of CPA were seen during a 6 month period. In 34 cases (26%) cardiopulmonary resuscitation (CPR) was attempted and 17 showed a positive response (recovery of cardiac automatism for more than 15 min). Median survival time in those who recovered was 38 hr. Only two patients were discharged alive from the hospital. Practice of CPR was strongly and inversely associated with the degree of anticipation on the occurrence of CPA held by the physician in charge. Age was the only variable prognostically associated with response to CPR, being the younger group (less than 40 yr) those with the worst prognosis. Aside of age and the possible beneficial effect of infection, there were no other demographic, clinical, therapeutic or other circumstances of the episode associated with response to CPR. The need of response systems to CPA, always in standby and reiterative training, is stressed. PMID- 2236970 TI - [Splenectomy in idiopathic thrombocytopenic purpura]. AB - Between January 1976 and December 1987, 44 patients with idiopathic thrombocytopenic purpura were submitted to splenectomy. This study analyzes the results of treatment and the usefulness of several prognostic markers. There were 38 female patients and six males with a median age of 28.5 years (range 11 to 66 years). Forty two out of 44 patients received preoperative steroids. Seventy five percent achieved a satisfactory response to this treatment but 31 relapsed (in eight recurrence was observed when the steroid dose was tapered). Eleven patients persisted symptomatic notwithstanding medical treatment. In two cases splenectomy was performed as an emergency procedure, and in one patient who was already in remission with previous steroid treatment, splenectomy was performed for other medical reasons. Operative mortality rate was 4 percent, and five patients developed postoperative complications (three had pneumonia, one pulmonary thromboembolism and one would infection). Eighty four percent of the patients were free of disease at one year followup survival at 10 year period was 80 percent. No correlation was found between age, duration of symptoms, previous response to steroids or time-period of medical treatment with the results obtained with splenectomy. PMID- 2236971 TI - [Plasma cells in the cerebrospinal fluid of patients with cerebral cysticercosis]. AB - We studied in twenty patients with proven cerebral cysticercosis the presence of plasma cells in the cerebrospinal fluid (CSF). We found plasma cells in 50 per cent of the patients. All of them had subarachnoid cysticercosis or basal arachnoiditis. The presence of plasma cells was significantly associated to higher protein levels, greater number of inflammatory cells, and higher levels of IgG in the CSF. None of the patients had received medical treatment or steroids prior to the test. These findings suggest a role of plasma cells in the pathogenesis of the cysticercotic disease. The presence of plasma cells in the CSF is part of the immune response against the parasite. We also found that plasma cells are more frequently encountered in the CSF (50 per cent) than eosinophils (20 per cent) in patients with cerebral cysticercosis. PMID- 2236972 TI - Pathophysiology of experimental nephrotic syndrome induced by puromycin aminonucleoside in rats. I. The role of proteinuria, hypoproteinemia, and renin angiotensin-aldosterone system on sodium retention. AB - The pathophysiology of the nephrotic syndrome (NS), characterized by protenuria, edema, sodium retention and hyperlipidemia, is not clear. We studied the role of some systemic factors on sodium retention in an experimental model of NS. NS was induced in rats by a single subcutaneous injection of puromycin aminonucleoside (PA) (15 mg/100 g); control animals received vehicle. All rats were kept in metabolic cages for 24 days (3 days before and 21 days after PA-injection). Urine was collected daily. Blood samples were obtained every day until day 10, and then every other day up to the end of the study. The rats showed the following alterations after PA injection: a) a rise in serum angiotensin converting enzyme activity (ACEA) and plasma aldosterone (PAldo) at day 1; b) a rise in urinary aldosterone (UAaldoV), azotemia and sodium retention at day 2; c) massive proteinuria (UProt) and decrease in plasma angiotensinogen concentration (PAC) at day 4; d) increases in plasma renin activity (PRA), plasma renin concentration (PRC) and serum creatinine as well as hypoproteinemia, hypercholesterolemia, hypertriglyceridemia, ascitis and edema at day 5; e) increase in urine volume at day 6. PAldo became normal at day 7; urine sodium (UNaV), PRA and PRC at day 8; UAldoV at day 9; serum urea and ACEA at day 10; urinary volume at day 11; PAC, serum total protein and creatinine at day 12. The edema disappeared at day 11. UProt, hypercholesterolemia and hypertriglyceridemia persisted, though they decreased substantially by the end of the study (day 21). Light microscopy studies revealed normal glomerular morphology, but electron microscopy showed fusion of podocytes before proteinuria. These data suggest that: a) sodium retention was not a consequence of proteinuria or hypoproteinemia; b) sodium retention seems non-related to renin secretion, but may be partially mediated by a fall in glomerular filtration rate or by an increased tubular resabsorption secondary to other factors; c) the increase in PAldo, UAldoV and ACEA are non related to renin secretion: all occurred before PRA rose; d) water retention, increase in PRA and PRC, hypercholesterolemia and hypertriglyceridemia are secondary to the hypoproteinemia. PMID- 2236973 TI - [Evaluation of the activity of creatine phosphokinase for the detection of carriers of Duchenne-type muscular dystrophy in families in the city of Monterrey, Mexico]. AB - The activity of serum creatine phosphokinase (CPK) was determined in 80 female members of 23 families with affected members of Duchenne type muscular dystrophy (DMD) and compared with the values of a control group of 100 unaffected women. The control group values exhibited a normal distribution of frequency with a mean of 21 U/L and standard deviation from the mean of 7.9 U/L. Sixty nine percent (11/16) of obligatory carriers showed CPK values higher than the mean of the control group plus two standard deviations of the mean. Thirty one percent (5/16) had false negative values. These percentages are similar to those reported in other studies. Elevated CPK activity was found in 45% (18/40) of type A possible carriers (relatives of obligatory carriers) and the group of possible carriers type B (mothers and relatives of isolated cases) 42% (10/24) exhibited high CPK values. Bayesian analysis was also used in all possible-carriers (A and B). We also report an estimation of the fertility of the DMD gene carriers and of their attitude towards family planning. It is concluded that the determination of serum CPK activity, despite its shortcomings, associated with Bayesian analysis when necessary, could be the method of choice for quick and inexpensive evaluation of the carrier status, mainly in families with members affected by DMD. PMID- 2236974 TI - [Diagnosis of thrombosis of cavernous sinus in magnetic resonance imaging]. AB - The diagnosis of the cavernous sinus thrombosis requires a careful clinical evaluation and appropriate radiological methods. In this report we describe the magnetic resonance imaging findings in a patient with the clinical diagnosis of cavernous sinus disorder and its correlation with orbital phlebography and histopathologic studies. PMID- 2236975 TI - [Oculopharyngeal muscular dystrophy: 1st report in Mexico]. AB - We report a case of a woman of Mexican origin with oculopharyngeal muscular dystrophy (OMD). This is the first OMD reported in Mexico. She was healthy until the age of 30, when she noticed slowly progressive ptosis and dysphagia. She developed dermatitis and polyneuritis which we attribute to a deficiency of nutrients due to her dysphagia. In contrast to most previous reported cases this patient had also a distal myopathy. It is recommended in this type of patients a strict dietary control in order to avoid complications. It is also recommended to perform biopsies of several muscles to complete the diagnosis and prognosis. PMID- 2236976 TI - [Ethical aspects of modern genetics]. PMID- 2236977 TI - [24-year-old woman with hematuria, mental changes, loss of visual acuity and ulcers on the fingers]. PMID- 2236978 TI - [Surgical risk and complications after major surgery in patients with cirrhosis]. AB - In this study we report the morbidity and the mortality observed in 55 patients with cirrhosis who had a major surgical procedure between October 1986 and June 1988, as well as its relation with different variables. The overall mortality was 34.5% and it was due to multiple organ failure or bleeding because of coagulopathy in 18 of 19 patients. The preoperative variables associated with major mortality were: emergency surgery, classification 3 or 4 of the American Society of Anesthesiology (ASA) and poor hepatic reserve evaluated with the Child Turcotte classification (the mortality for A group was 16%, B 62%, and C 100%). The transoperative hypotension increased the mortality 4.5 times. In the postoperative period an elevated APACHE (Acute Physiologic and Chronic Health Evaluation) II score (mortality of 100% in those with greater than 20 points), multiple organic failure (100% died with 2 or more organ failures) or surgical reintervention in the patients with Child A increased significatively the mortality. The 24 patients who survived without complications were discharged on the 19th day (+/- 9 S.D.), while those with complications stayed during 46 days (+/- 18 S.D.). PMID- 2236980 TI - The role of nutrition in the management of dermatoses. PMID- 2236979 TI - Nutritional influences on immunity. AB - There is no doubt that nutrient deficiencies and excesses can influence immune responses. Despite advances in the development of therapeutic agents, a competent immune system is crucial for prevention and resolution of disease. Leukocytes are some of the most metabolically active cells in animals. We know that growing animals require nutrients to sustain growth and reach their full potential, whether that is size, strength, speed, or agility. We do not expect kittens to grow or greyhounds to run without provision of adequate nutrients. To expect the immune system to function in the face of nutrient deficiency neglects our knowledge of the physiological needs of metabolically active tissues. Immune responses may be modified through dietary manipulations. However, the clinician must answer the question "to what end or consequence will the response be changed?" No "golden" nutrient ensures an appropriate immune response in all conditions, just as no "golden" drug heals all diseases. Our knowledge of nutrient-immune system interactions is increasing. Yet, for all of the current knowledge of nutrient effects on immunity, the words of Dr R.K. Chandra hold sterling advice, "Moderation is a good dictum in biology and medicine, and it applies equally to nutritional immunology." PMID- 2236981 TI - Nutritional management of diabetes mellitus. PMID- 2236982 TI - Nutritional management of chronic renal failure. PMID- 2236983 TI - Nutritional support in the surgical patient. PMID- 2236984 TI - Renal nutrition. PMID- 2236985 TI - Energy and fuel substrate metabolism in the kidney. PMID- 2236986 TI - Amino acid metabolism in the kidney. PMID- 2236987 TI - Glucose metabolism and the kidney. AB - Although the kidney both takes up and produces glucose, its net contribution to overall glucose homoeostasis is negligible since these two processes approximately counterbalance each other. Glucose uptake primarily occurs in the distal medullary segments of the nephron where the glycolytic enzymes are present in high concentration. The major metabolic fates of the glucose which is taken up by this region of the kidney are oxidation to carbon dioxide and conversion to lactate. In contrast, gluconeogenesis primarily occurs in the proximal tubular portion of the renal cortex where free fatty acids represent the major metabolic fuel which supplies the energy requirements of the cell. However, in certain conditions, including metabolic acidosis, prolonged fasting, and poorly controlled diabetes mellitus, renal gluconeogenesis can be enhanced markedly and a net output of glucose by the kidney is readily observed. PMID- 2236988 TI - Nutritional factors affecting renal growth and hypertrophy. PMID- 2236989 TI - Factors controlling intracellular protein turnover in the kidney. PMID- 2236990 TI - The effect of the nephrotic syndrome on the renal handling of protein and other nutrients. PMID- 2236991 TI - The effect of amino acids on ischemic and toxic injury to the kidney. PMID- 2236992 TI - [Controversy over brain death in Japan]. PMID- 2236993 TI - Three-dimensional observation of the rat endocrine pancreas by a scanning electron microscope. AB - A three-dimensional observation was performed on chemically digested rat pancreata and vascular corrosion casts of it with a scanning electron microscope. The Langerhans islets were sporadically situated in the exocrine tissue and were surrounded by the fibrous capsule, which was so tough that it could not be chemically digested easily. This capsule was considered to play different roles in the collection of the endocrine cells in a functional unit, in the prevention of secreted hormones spreading into the adjacent exocrine and stromal tissue, in the support of the microvascular structure, and in the protection for the islet cells from the pancreatic enzymes, which are leaking into the stromal spaces physiologically. The microvascular structure of the islet, disclosed by the corrosion vascular casts, showed afferent vessels branching into the capillaries at the periphery of the islet and entering the core of it by a twisted course. These findings were considered to be related to the islet cell distribution, that is, A and D cells are at the periphery of the islet and B cells at the center of it. This might support the existence of a hormonal regulating mechanism among endocrine cells. In addition, the efferent vessels from the islet that communicate to the vascular network of the exocrine tissue might suggest that the endocrine system also regulates the exocrine function in a circulatory dynamic state. PMID- 2236994 TI - [Image analytic studies of melanin granules of human hairs with transmission electron micrographs]. AB - Using electron micrographs of human hairs, we measured the minor axis and density of melanin granules by an image analyser. The melanin density of the outer hair cortex was higher than that of the inner hair cortex, and significant differences were evident especially in the minor axis and density of melanin granules among individuals. These quantitative analyses as to the minor axis and density of hair melanin granules are a reliable tool for the measurement of hair color. PMID- 2236995 TI - [Effects of sex difference on the toxicity of ethylene oxide. IV. Anemia]. AB - Wistar male and female rats were exposed to ethylene oxide (EO) at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks simultaneously, and the sex difference of anemia induced by EO was investigated. Hemoglobin concentrations of both the male and female exposed groups were decreased when compared with each control group, and the anemia in the female exposed group was more severe than that in the male exposed group. Absolute spleen weight increased only in the female exposed group. We have already reported that a decrease of the glutathione reductase activity in the erythrocyte plays an important role in the EO-induced anemia. In the present study, the activity in both male and female exposed groups decreased when compared with each control group, and there was no sex difference in the degree of the decrease. From these observations, we concluded that there was a sex difference in the EO induced anemia. PMID- 2236996 TI - Sarcoid reaction observed in a worker with a history of asbestos exposure. AB - Bilateral hilar and mediastinal lymphadenopathy was observed in a 32-year-old man who had been engaged in asbestos spraying for 16 years. Lymph nodes obtained from Daniel's biopsy revealed tissue reaction compatible with sarcoidosis. On the other hand, a large number of asbestos particles were detected in the lung tissue from transbronchial lung biopsy and in bronchoalveolar lavage fluid, but no epithelioid granuloma was observed in the lung tissue. Various immunoserological findings such as PPD skin test, serum angiotensin converting enzyme activity, serum beta-glucuronidase and lysozyme level, serum antinuclear antibody, lymphocyte subset of blood and bronchoalveolar lavage fluid were inconsistent with sarcoidosis. However, lymph node enlargement and immunological abnormalities in this patient may be related to asbestos exposure and may not have occurred merely by chance. PMID- 2236998 TI - [Topographic mapping: thoughts on the past and the future]. PMID- 2236997 TI - [An autopsy case of acute interstitial pneumonia]. AB - An autopsy case of a 77-year-old male with acute interstitial pneumonia (AIP) is reported. The patient died of respiratory failure in the extremely rapid course of 8 days. The histogenesis of the thickening of the alveolar wall and the intraluminal lesions were noticed. Incorporation of the hyaline membrane as well as the intraseptal edema and septal cell proliferation played an important role in the fibrous thickening of the alveolar wall. The intraluminal granulation tissue was observed in the alveolar space and the alveolar duct, often extending into the respiratory bronchioles. Intraluminal granulation tissues in the alveoli frequently had the appearance of intraluminal buds of mesenchymal cells, so called Masson's bodies, and there was little remodeling of pulmonary structures in this case. These findings suggest an acute, diffuse and severe damage of the peripheral respiratory tract and are consistent with bronchiolitis obliterans with classical interstitial pneumonia (BIP) by Liebow and AIP by Katzenstein. This patient had suffered from suspected "Bronchiolitis obliterans organizing pneumonia" (BOOP) one and half years ago. The relationship between AIP, BIP and BOOP is discussed. PMID- 2236999 TI - Alcoholism recovery in lesbian women: a theory in development. AB - Utilizing the modified practice-theory strategy for theory building, a provisional theoretical model was developed to describe alcoholism recovery in lesbian women. Assumptions are acknowledged, key concepts are identified, and propositions are formulated for the purpose of generating nursing knowledge about a significant health problem in this aggregate of women. The theory's implications for nursing research, practice, and further theory development are discussed. PMID- 2237000 TI - Effects of antepartal stress on health status during early motherhood. AB - A group of high-risk women who were hospitalized for a pregnancy-risk complication, and a group of low-risk women experiencing normal pregnancy were compared for differences in health status and the effects of antepartal stress on their health status from pregnancy through early motherhood. High-risk women reported a statistically significant poorer health status during pregnancy, early postpartal hospitalization, and at eight months following birth. High-risk women reported greater stress from negative life events in addition to their greater pregnancy risk. Among both groups of women, negative life events' stress had indirect effects on health status over time through either self-esteem, family functioning, mate relationships or perceived support. The effects of a high-risk pregnancy on health status were evident at eight months following birth; high risk women's feelings about their pregnancy and the extent of stress from hospitalization had direct effects on their health status, while negative life events had indirect effects. PMID- 2237002 TI - Personal control and other determinants of psychological well-being in nursing home elders. AB - The purpose of this correlational study was to identify predictors of psychological well-being in nursing home elders. Predictors considered were two dimensions of personal control, physical health, functional health, socioeconomic status, length of stay in the nursing home, and interaction variables. The nonrandom sample consisted of 302 cognitively intact nursing home elders with poor to excellent self-rated physical health. Instruments used included the Life Satisfaction Index A, Affect Balance Scale, Desired Control Measure, The Index of Activities of Daily Living, and The Two Factor Index of Social Position. Regression analysis demonstrated that dimensions of personal control and self rated physical health explained 33% (p less than .001) of the variance of psychological well-being. Findings suggested predictor variables to guide the promotion and maintenance of psychological well-being in the subjects of this sample. PMID- 2237001 TI - Personal knowing: evolving research and practice. AB - Personal knowing is essential to the development of knowledge central to the practice of nursing. Personal knowing as a process of research within practice is conceptually developed through definition, components, attributes, and examples. Although personal knowing, i.e., discovery of self-and-other arrived at through reflection, synthesis of perceptions, and connecting with what is known, has been identified as a fundamental way of knowing for nursing (Carper, 1978), the process has not previously been systematically developed or tied in with the theoretical, syntactical, and practice structures of nursing. In this article, an increased emphasis on personal knowing within the research and practice domains of nursing is proposed, and implications and questions are raised regarding implementation. PMID- 2237003 TI - [The sociocultural correlates of psychopathic personalities]. PMID- 2237004 TI - [Clonidine treatment in manic episodes]. AB - The authors have treated 20 patients hospitalized for acute manic disorders with 450-750 micrograms of clonidine per day for a period of one month. The tolerance to the drug was excellent. A marked decrease in manic symptoms was noted in 65% of the patients after the first ten days of therapy. The response was rapid and was maintained for the entire duration of the study, and clonidine was efficient for all the symptoms of the manic syndrome. The supra-sedation effect was much lower than with neuroleptics, and clonidine could be considered to represent a practical progress in the acute therapy of manic patients. Clonidine, usually employed as an anti-hypertensive drug, is an alpha-2-adrenergic agonist. It is believed that this property decreases the neural transmission by noradrenaline by stimulating pre-synapsis inhibitor receptors. PMID- 2237005 TI - [The types of remission in schizophrenia in students. A clinical catamnestic study]. PMID- 2237006 TI - [Observations on deaths in alcoholism]. AB - The present study is an attempt to establish the death rate of alcoholic patients with their various psycho-organic complications. The study was done on cases of alcoholic patients hospitalized in our Clinic over the past three decades. Thus, if the mortality index in 46,591 psychic patients hospitalized between 1959 and 1988 was of 0.36%, in alcoholics (totalling 5,580 of all patients) the mortality index was of 1.97%. An analysis of these figures with the aid of the X-square method showed a p of less than 0.001, indicating a significant difference with a probability of over 99.90% between these two groups of patients. PMID- 2237008 TI - [Transient global amnesia (a study of 30 cases)]. AB - The authors have studied 30 patients with transient global amnesia aged between 49 and 76 years (median age of 63 years), without focal neurologic signs that have been followed for periods varying between 6 months and 10 years. Three of the patients had recurrent attacks of transient global amnesia, and another three had a stroke, although at some distance from the amnesia attack. Association was noted with certain risk factors including high blood pressure, and angiopathic changes of the eye fundus (in 50% of the patients), dyslipidemia (in 30%), diabetes (in 10%), and essential polyglobulia (in 7%). Coagulation studies including thrombelastograms were carried out in 22 patients, and demonstrated hypercoagulability in 50% of them. Changes in the arterial wall were noted in 85% of the 14 patients in whom carotid sphygmograms were recorded. The presence of these risk factors could explain the occurrence of cerebrovascular accidents in patients with transient global amnesia. Electroencephalograms performed immediately or a short time after the amnesia attack have evidenced in 18 patients rapid-type dysrhythmia, or diffuse theta waves, predominantly located in the deep layers of the left and right temporal areas. The EEG tracings were either flat or normal in the remaining 12 patients. Of the 30 patients presenting with global transient amnesia only two had migraine in antecedents, and another six had headache during the evolution of amnesia. The neurologic examination did not reveal any abnormality in 27 of the patients. Sequelar signs of neurological deficits were noted in the remaining three patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237007 TI - [Olivopontocerebellar atrophy in the context of progressive cerebellar atrophies (a clinico-anatomical study)]. AB - The study of 15 cases of progressive cerebellar atrophies, and especially of the olivopontocerebellar atrophy, that was investigated both clinically and anatomically, has attempted to evidence particularities and correlations existing between these two types of atrophy. Olivopontocerebellar atrophy appears to be an abiotrophy of the cerebellum, considered to be spontaneous, sporadic, and sometimes with a hereditary familial background. It is a systemic disease, predominantly of the neocerebellum and involving the cerebellopedal system. It is at the opposite end of Holmes-type atrophies, and of the cerebello-olivary atrophies of the young (I. T. Niculescu, Th. Hornet, 1936) which mainly involve the paleocerebellum. The disease has a polymorphous symptomatology, it has a slow, progressive evolution with mostly cerebellar signs, with extrapyramidal phenomena and psychical disturbances due to lesions of the telencephalic pathways, and sometimes of the spinal, cerebellar and bulbar proprioceptive afferences, with spinal and bulbar involvement (Cezar Ionel, 1949, 1972). PMID- 2237009 TI - [Calcification of the cerebral hemispheres in an infant. A clinical case]. PMID- 2237010 TI - [The diagnosis of cerebral lesions by stereotaxic biopsy]. PMID- 2237012 TI - [Cutaneous tuberculosis, a forgotten disease?]. PMID- 2237011 TI - [Risk factors in cerebral ischemic vascular diseases and their primary prevention]. PMID- 2237013 TI - [Stress of medical origin and "education" of the patient]. PMID- 2237014 TI - [Therapeutic strategies in pregnancy bacteriuria]. PMID- 2237015 TI - [Post-concussion vertigo. Vertigo of cervical origin]. PMID- 2237016 TI - [Importation of animal and human tropical myiasis by Cochliomyia hominivorax (Coquerel) in Libya (diptera: Calliphoridae)]. PMID- 2237017 TI - [Splenectomy]. PMID- 2237018 TI - [Electronic gas analyzer]. PMID- 2237019 TI - [Growth disorders. Treatments]. PMID- 2237020 TI - [Growth disorders. Surgical lengthening by external fixators]. PMID- 2237021 TI - [Growth disorders. Ilizarov fixator]. PMID- 2237022 TI - [Growth disorders. Initial project and realization]. PMID- 2237023 TI - [A problem of height]. PMID- 2237024 TI - [Delegation]. PMID- 2237025 TI - [The nursing assistant in the patient care team]. PMID- 2237026 TI - [Growth in length of lower limbs]. PMID- 2237027 TI - [Our systems of retirement. The future]. PMID- 2237028 TI - [Echoguided kidney puncture biopsy]. PMID- 2237029 TI - [The world situation of AIDS]. PMID- 2237030 TI - [Growth delays in children]. PMID- 2237031 TI - Performance variables associated with the competitive gymnast. PMID- 2237032 TI - Thermoregulation in pregnancy. Implications for exercise. AB - Studies concerning exposure to heat during pregnancy have indicated that maternal hyperthermia can be teratogenic, causing primarily CNS abnormalities. Data, using the animal model, have consistently indicated that the effects of heat are most hazardous when exposure occurs in the first trimester of pregnancy. However, the human data from retrospective studies and sauna bath exposure are not conclusive. Since the risk potentially exists, physicians have been advising expectant mothers to avoid self-inflicted conditions that may result in core temperatures above 38.9 degrees C (102 degrees F). Research has indicated that exercise can result in core temperatures above the recommended level. Considering that early in pregnancy the mother may not appreciate her pregnancy and could exercise at high intensities, the possibility of exposing the fetus to hyperthermia exists. Of the limited studies of exercising pregnant women, there are no data suggesting that normal women actually exercise to a level of exertion that causes significant hyperthermia. However, these studies have been limited to nonathletic populations, in which the exercise has not been prolonged and of high intensity, or sufficient to induce dehydration. Other data indicate that if hyperthermia is a potential consideration for the exercising mother, then exercise in the water may be better as it provides for greater heat loss. The data concerning exposure to cold, although sketchy, suggest that unless the hypothermia is detrimental to maternal survival, there is minimal risk to the fetus. PMID- 2237035 TI - Athlete's nodules. Treatment by surgical excision. AB - Athlete's nodules are connective tissue nevi of the collagen type (collagenomas) which appear as thick dermal masses at sites of chronic trauma. They have been described as occurring on the dorsum of the feet, knees, and knuckles of surfers, boxers and marble players. Recurrent minor blunt trauma and pressure are aetiological factors in this condition. We report a 54-year-old man with dermal nodules on the dorsal surface of his feet. These lesions initially appeared during his participation as a player on a high school football team. They were attributed to the chronic pressure of his high-laced athletic sneakers and frequent minor injuries to the involved areas. We describe the successful treatment of our patient's lesions by surgical excision. We also discuss the differential diagnosis and other therapeutic options for athlete's nodules. PMID- 2237036 TI - [What is your diagnosis? Osteoid osteoma]. PMID- 2237033 TI - The assessment of physical activity by leisure-time physical activity questionnaires. AB - The assessment of physical activity by questionnaire is currently the most popular and practical method of quantifying physical activity levels. Many questionnaires, past and present, have considered overall or habitual physical activity, which includes occupational (or nonleisure) activity. Others have focused specifically on leisure-time physical activity (LTPA) owing to the recognition of its dominating contribution to the total physical activity of developed populations. This review covers questionnaires that wholly or in part attend to LTPA levels. Typically, self-complete or interviewer-administered questionnaires record information on the types, frequency and duration of activities performed over a particular period of time. Activity-specific energy cost values, expressed in metabolic equivalents (METS) or kilocalories, are then commonly used to estimate the total energy expenditure from all activities and/or categories of activities. The validation of LTPA questionnaires has had to rely upon indirect methods, such as the assessment of cardiorespiratory fitness, body composition and activity diaries. The reporting of the reliability of questionnaires has frequently been ignored, although in cases where it has been reported, doubt exists as to whether the consistency of the questionnaire or the consistency of subjects' physical activity habits were being examined. LTPA questionnaires first appeared in the literature in the mid-1960s for use among specific, mainly middle-aged male population groups. Though they varied in their modes of scoring, periods of activity recall, and overall complexity, associations were universally observed between physical activity levels and chronic health conditions. However, it became apparent that different questionnaires did not yield the same results. In 1978, a questionnaire to assess only LTPA, the Minnesota LTPA Questionnaire, was published and despite its substantial limitations, has since established itself as the most popular option available. In recent years, shorter and simpler alternatives have been advocated, though most have yet to be adequately scrutinised. Associations have been found between LTPA and fitness levels, prompting the use of LTPA questionnaires in large-scale fitness surveys of both adults and children. Although LTPA has continued to be estimated in terms of energy expenditure, little attempt has been made to extend existing knowledge on the energy cost of physical activities. Existing values do not accommodate for individual intensities and inter population activity variations. Consequently, standardised questionnaires are not yet viable. There exists considerable scope for further work with LTPA questionnaires, especially since the association between coronary heart disease and physical activity is now well recognised. Efforts ought to be directed at wider social groups for whom leisure-time activity may have distinct implications. PMID- 2237037 TI - [Femoral neck fractures]. PMID- 2237038 TI - [The eye as a reference organ for diseases of the nervous system. Simple examination methods for office practice and at the bedside]. AB - The eye is not only for vision. In diseases of the nervous system it can fulfill the task of a diagnostic tool. As a highly developed sensory organ, the eye is affected by disorders of the visual pathways, the pupillo-motor structures or the ocular motor system. Several simple clinical tests are presented which can be performed in practice or at the bedside without any technical equipment. PMID- 2237034 TI - Erythrocytic system under the influence of physical exercise and training. AB - It is obvious that physical performance, endurance capacity and resistance to fatigue in humans are dependent upon many different factors. One factor, the oxygen carrying capacity of blood, seems to be of particular importance. This factor is mainly determined by haemoglobin concentration, number of circulating erythrocytes and the efficiency of their functions. A single bout of physical effort and, even more, repeated exercise may change the morphological indices of blood and influence the erythropoietic processes in the bone marrow. That is why there is so great an interest now attached to the effects of physical exercise on the erythrocytic system. Although in recent years many papers have been published on the subjects their findings pertaining to the effects of single bouts of exercise and systematic training on the erythrocytic system are often contradictory. The haematological parameters in some top-class athletes, particularly those performing in endurance disciplines are lowered at rest. Anaemia has been described in sportsmen, even among the members of Olympic teams. This type of anaemia has been called 'sports anaemia', 'athletes' anaemia' or 'postexercise anaemia' in order to emphasise its character. Among many possible causes which may bring about the development of sports anaemia the most commonly recognised are: postexercise plasma expansion, intensified haemolysis during physical efforts, iron deficiency, losses of erythrocytes by the way of bleeding into the digestive and urinary systems and also some disturbances in erythropoiesis. However, there is evidence of the intensification of erythropoiesis by many factors occurring during physical exercise. PMID- 2237039 TI - [Recurrent inguinal hernia]. AB - Recurrence is the most common complication after operation for inguinal hernia. A first recurrence is seen in 1 to 10%, depending on the type of operation. Recurrence rates up to 39% are observed after multiple recurrences. After a mean follow-up of 8.8 years we found 238 recurrences, in 52% lateral, in 41% medial and in 7% combined ones. The follow-up showed that the probability to acquire a new recurrence after operation for recurrent hernia rises with increasing numbers of recurrences. Age is without influence on recurrence formation. In 37% of the operations the primary inguinal hernia repair was performed in the same hospital. In this group of patients no correlation was observed between recurrence and illness with raised intraabdominal pressure or lipomas of the cord. In 47% we found lateral recurrent hernias, after medial recurrences one third of the patients were presented with a new recurrence, and after combined hernias about 20% had a new recurrence. Beside various discussed factors it seems that the operation technique mostly influences the result of the operation. PMID- 2237040 TI - [Vertebral and costal stippling. A pitfall in scintigraphy]. AB - Bone scintigraphy is largely used for diagnosis and surveillance of osteoarticular diseases. Interpretation of fortuitous increased isotope accumulation elsewhere on the skeleton may be difficult. We report a man with a peripheral seronegative inflammatory arthropathy, whose bone scintigraphy disclosed stippled ribs and vertebral increased isotope uptake, corresponding to rib enthesopathy and vertebral hyperostosis. Better knowledge of these unusual pictures should prevent further unnecessary investigations. PMID- 2237041 TI - [Myoma in pregnancy--a case report and a literature review]. AB - We report the complications of uterine leiomyomas during pregnancy in a case report and a review of the literature. The major complication is the syndrome of painful myomas. Other problems are premature labor, abruptio placentae and postpartum hemorrhage. The method of delivery seems not to be influenced by uterine myomas. Leiomyomas are no contraindication for pregnancy, but intensive antenatal care is advised. PMID- 2237042 TI - [Tenosynovial giant cell tumor in the differential diagnosis of painful heel]. AB - Based on a case report regarding a patient with a tenosynovial tumor in the calcaneal spur area, we present a compilation of the differential diagnoses in the event of heel pain. The diagnostic procedure is dealt with peripherally. As to the various therapeutic possibilities, we refer to the literature. PMID- 2237043 TI - [A case from practice (191). Acromegaly due to microadenoma of the hypophysis with cardiomyopathy and arterial hypertension]. PMID- 2237044 TI - [A case from practice (192). Cryptogenic peripheral facial paralysis (Bell's palsy)]. PMID- 2237045 TI - [Control of diabetes and late complications]. AB - When insulin was introduced in medical therapy in 1922, it permitted to save diabetics from premature death; however, it has allowed, after a certain period of time, for the appearance of a cohort of chronic complications connected more or less specifically to the degree of hyperglycemia. After a short review of the pathophysiology of the microangiopathy, the authors have tried to demonstrate, on the basis of numerous prospective and retrospective studies in the human as well as in the animal, that an important relationship exists between the degree of glycemic control and the severity of the classical complications, retinopathy, neuropathy and nephropathy. However, the most recent studies have stressed the role of some other factors, not well established in the past, as for example the potential negative impact on retinopathy of rapid normalization of glycemia, following a long period of poor metabolic control. Likewise, high blood pressure, smoking, genetic background, as well as probably also excess of protein intake, do play an important etiopathogenic role. Thus, the simplistic equation hyperglycemia = complications is not completely valid. Microangiopathic risk in insulin-dependent diabetics seems to be low as long as their HbAlc is below 7.5%, and they do not have hypertension and do not abuse tobacco. Finally, the general approach to therapy is redefined: Try to get as close as possible to near normoglycemia by multiple insulin injections, without causing, however, major hypoglycemia; this should be done very early after the onset of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237046 TI - [Dyslipidemia in diabetes mellitus: significance, diagnosis and treatment]. AB - Dyslipidemias are frequent in diabetic subjects: they increase the risk for atherosclerosis, in addition to the risk of diabetes mellitus per se. The pathogenesis of dyslipidemias differs between type I and type II diabetes: untreated type I diabetic subjects demonstrate frequently increased triglyceride concentrations due to diminished removal of triglyceride-containing particles, as a result of diminished activity of lipoprotein lipase. In addition, more triglycerides are produced due to increased lipolysis and increased free fatty acid supply to the liver. Type II diabetic subjects demonstrate very low density lipoprotein (VLDL) over-production due to obesity, insulin resistance and caloric overconsumption. In addition, triglyceride removal may be diminished due to diminished lipoprotein lipase activity when diabetes mellitus is poorly controlled. In addition, high density lipoprotein (HDL) is frequently lowered. During decompensation low density lipoprotein (LDL) concentrations may also increase. LDL particle composition is frequently abnormal. A severe dyslipidemia in diabetes mellitus is frequently a combined effect of diabetes mellitus and a congenital lipoprotein abnormality. The evaluation and treatment of dyslipidemias in diabetic subjects should be performed similarly to non-diabetics according to the guidelines published recently by the Working Group 'Lipids' of the Swiss Foundation of Cardiology. Additional accents in diabetic subjects are necessary. It is recommended that serum cholesterol, triglycerides and HDL are determined in every patient when diabetes mellitus is diagnosed. If serum cholesterol is greater than 6.5 mmol/l and the cholesterol/HDL-ratio is greater 6.5, dietary treatment should be reinforced; if its effect is insufficient, drug therapy should be considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237047 TI - [Diabetic retinopathy]. AB - The risk of blindness in diabetes may be significantly reduced by a suitable ophthalmic therapy. In order to apply this therapy in due time to the population at risk, all diabetics should be referred to ophthalmological follow-up examination at regular intervals. A rapid progression of a retinopathy may occur in young patients, especially during puberty and pregnancy, after change from oral antidiabetics to insulin and, temporarily, following strict control of blood glucose. Besides normoglycemia, the prevention of a high blood pressure is an important prerequisite of an efficient treatment of diabetic retinopathy. Retinal photocoagulation has been proven the most effective mode of therapy. The correct indication and stage-depending dosage of retinal laser coagulation in diabetes is a demanding task which should be reserved to well-trained specialists in this field. Diabetic vitreous bleeding and retinal traction detachment are complications of advanced proliferative diabetic retinopathy, which can be treated successfully in 60-70% of the cases by modern techniques of vitreoretinal surgery. PMID- 2237048 TI - [Diabetic neuropathy]. AB - Neuropathy is a frequent late complication of diabetes. The severity and duration of hyperglycaemia are probably the principal causal factor. The consequences of the effects of neuropathy on the lower-limb and the autonomic nervous system are major causes of morbidity. Apart from glycaemic control, no specific treatment is yet available, but measures for symptomatic alleviation of certain painful and visceral manifestations of diabetic neuropathy exist and are outlined in these guidelines. The guidelines also describe simple diagnostic strategies for detecting potentially threatening neurological signs, notably reduction or loss of lower-limb sensation which expose the patient to the risk of ulceration, unnoticed trauma and amputation. The guidelines also summarize the preventive educational measures required to minimize these risks. PMID- 2237049 TI - [Social and economic aspects in diabetes mellitus]. AB - The possibility of obtaining health and accident insurance as well as participation in a pension scheme does not pose any problems for diabetics in Switzerland. However, for a life insurance contract, the diabetic must often pay a surplus. The socio-medical evaluation for invalidity insurance for diabetics is based upon an eventual decrease in efficiency associated with functional alteration of certain organs. Diabetics treated only by dietary means can exercise any profession. When treated with oral antidiabetic agents or insulin, certain professions are discouraged, particularly when a metabolic crisis might be hazardous to the diabetic or a third party. Treatment of active diabetics most often aims at obtaining normoglycemia. This should enable patients to follow a physically active, even irregular life in their profession, studies and leisure without excessive risk. PMID- 2237050 TI - [Teaching and education of diabetic patients]. AB - The instruction of the patient with diabetes mellitus, aimed at the mastery of technical elements in self-management, as well as his/her education to a coherent behavior respecting both the quality of metabolic control and the quality of life, are basic elements of diabetes treatment. To neglect them would be a professional error. The physician in charge of a diabetic patient must take into account the knowledge and the capabilities that have been acquired by the patient before, as well as his/her actual demand for information and instruction. Concepts and methods of learning and teaching for diabetic patients that have been developed and applied over the last decade may serve as reference for all levels of health education. PMID- 2237051 TI - [Immunosuppression in Type I diabetes mellitus]. AB - The etiopathogenesis of type I or insulin-dependent diabetes mellitus is not known in details. It is now generally accepted, that type I diabetes is the result of an autoimmune disease. Type I diabetes begins after the destruction of 80-90% of insulin-producing beta cells in the pancreas. This knowledge let to immune intervention trials with various immunosuppressive drugs, especially cyclosporine A. These studies are still in an experimental stage. Because of inefficiency and severe side effects of these drugs, the med.-scientific section of the Swiss Diabetes Association recommends not to use immunosuppressive drugs in newly diagnosed patients with type I diabetes. PMID- 2237052 TI - [Semiautomatic insulin injection equipment (pens)]. AB - To the best of our knowledge, a good glycaemic control must be advised to avoid or delay the degenerative complications of diabetes, bearing in mind an increased risk of hypoglycaemias. Among other techniques, a treatment consisting of multiple injections (basal-bolus concept) is one way to achieve a good control. Although this form of treatment is rather restrictive (frequent blood glucose determinations), the use of pens makes it more acceptable. A fully informed and cooperative patient is a prerequisite before considering this particular type of insulin therapy which, however, is usually not very helpful for older diabetics. It is a misconception to think that every patient receiving insulin should do so with a pen, just as it is incorrect to recommend multiple injections for all type I diabetics. Whether such a therapeutic strategy is indicated should be established for each patient individually. In addition, the fashion for pens should not distract us from all the other problems associated with inadequate diabetic control, such as foot care and systematic blood pressure measurements. PMID- 2237053 TI - [Insulin injection/insulin pharmacokinetics]. AB - Whereas the importance of changing dietary composition and physical activity for metabolic control in diabetic patients is well respected, pharmacokinetic variables of insulin are often neglected in therapeutic decisions. The ambitious goal of euglycemia can rearly be achieved, however, without a profound knowledge of factors influencing the pharmacokinetics of insulin, such as site of injection, injection technique, miscibility of insulins, dose of insulin, injection volume, local blood flow, etc. Available data indicate that it is of major importance to implement pharmacokinetic aspects in the daily care of the insulin-treated patient. PMID- 2237054 TI - [Insulin treatment of Type II diabetes]. AB - Secondary failure to oral hypoglycemic agents occurs in some 5% of type II diabetic patients per year, such that treatment with insulin becomes warranted. In most of the cases only hyperglycemia is apparent, while signs of severe metabolic derangement such as thirst, polyuria and weight loss are lacking. However, the hyperglycemic state adversely affects endogenous insulin secretion and favors the development of microvascular complications and neuropathy. In addition, dyslipidemia is often present, and the patient's well-being may be impaired. To differentiate between real secondary drug failure and transient metabolic impairment due to insufficient compliance with the diet prescriptions, plasma C-peptide should be measured. Insulin therapy should be initiated with a dose of 6-8 IU of an intermediate-action preparation and subsequently adjusted based on blood glucose measurements. Frequently it will be necessary to employ twice daily a mixture of (rapid- and intermediate-action) insulin in order to achieve adequate control of postprandial hyperglycemia. In some cases insulin therapy can be discontinued since the endogenous insulin secretion may improve during insulin treatment. We do not recommend to use as initial therapy of patients with secondary failure to oral hypoglycemic agents a combination of sulfonylureas and insulin since the 'insulin-saving' effect is small and not cost effective. PMID- 2237055 TI - [Human insulin and hypoglycemia]. AB - It has been reported over the last few years that transferring diabetic patients from animal to human insulin can lead, in some of the patients, to a diminution of the classical hypoglycaemic symptoms, as hunger and sweating, and to the more frequent occurrence of neuroglycopenic symptoms, as the first manifestation of hypoglycaemia. These changes seem to involve a fraction of patients estimated between 8 and 36%, depending on the type of selection of the patients. A decrease in the adrenergic counterregulatory response to hypoglycaemia has also been shown in some studies with human insulin. Similar changes in the sequence of hypoglycaemic symptoms are also described in various clinical conditions--as intensive insulin therapy with tight glycaemic control, long diabetes duration and presence of autonomic neuropathy, thus acting as confounding factors. According to these facts, a few recommendations are proposed: briefly, human insulin should only be prescribed to new patients who are able to learn from the very beginning the sequence of hypoglycaemic symptoms with human insulin; patients already treated with porcine insulin should not be transferred to human insulin. On the whole, studies available to date have not shown an increased frequency of severe hypoglycaemia with human insulin; however, this important matter still has to be conclusively clarified through well-designed prospective studies. PMID- 2237056 TI - [The AIDS virus does indeed originate from Africa]. PMID- 2237057 TI - [What is your diagnosis? Atrial myxoma]. PMID- 2237058 TI - [Cutaneous manifestations of tuberculosis]. AB - Tuberculous lesions of the skin occur rarely nowadays. We therefore have mostly lost the knowledge to recognize this entity. Furthermore, the great variability of the clinical and particularly dermatologic manifestations of the disease can tax the most astute clinician. The challenge is even greater, when the patient has an intercurrent condition such as a malignancy or AIDS. In order to make understanding easier, we replace all descriptive terms, some carried over from the last century, by a useful pathogenetic and clinical, algorithmic classification. Finally the necessity of biopsy and specific cultures for proper diagnosis and treatment of any skin lesion consistent with skin tuberculosis is emphasized. PMID- 2237059 TI - [Pasteurellosis in human pathology]. AB - Pasteurella are common bacteria among healthy animals. Humans usually are infected by dog and cat bites or scratches. Besides, local skin infection, Pasteurella may spread, in some cases, to lungs, joints, bones or, less frequently, to other organs. PMID- 2237061 TI - [Hand dermatoses in children]. AB - Dermatoses of the hand in children are part of an original entity which can be classified in two groups: a group involving exclusively the hands and another one which is predominantly involving the hands. Attention has been focussed mostly on hand dermatoses in children (acropustulosis of infancy, papular, acrodermatitis, hand foot and mouth disease, subungual, exostosis). We discuss also the diagnostic and therapeutic aspects of scabies in children. PMID- 2237060 TI - [Cyclosporin in dermatology]. AB - Cyclosporin is a potent immunosuppressive agent with a selective and reversible inhibitory effect on helper T lymphocytes functions mainly interleukin-2 production. Cyclosporin has no myelotoxic, mutagenic or teratogenic effect. The drug is effective in preventing organ rejection, as well as in various auto immune and inflammatory diseases. In dermatology the drug is extremely effective in psoriasis. Low doses (less than 5 mg/kg per day) have to be used to decrease the risk of nephrotoxicity and hypertension. PMID- 2237062 TI - [What is your diagnosis? Seropositive chronic polyarthritis in pregnancy]. PMID- 2237063 TI - [Diagnostic and therapeutic aspects of the initial epileptic seizure]. AB - We present the concept of an 'epileptic syndrome' which is important for prognostic statements and the application of appropriate therapeutic measures. We then discuss the epileptic seizure and the assessment of suspected seizure, indications for admission to a hospital, diagnostic measures (EEG, CT scan, laboratory tests, lumbal puncture, MRI scan, PET scan, angiography), therapy and procedures for imminent status epilepticus. Finally, we try to answer the question whether anticonvulsant medication should be instituted after a first epileptic seizure. PMID- 2237064 TI - [Hemiplegia: diagnosis and differential diagnosis]. AB - Hemiplegia is the most frequent form of paralysis in humans and involves face, arm and leg on one side of the body. Diseases localized in the cortex, the cerebral white matter (corona radiata) and the internal capsule usually manifest themselves by weakness or paralysis of the face, the arm and the leg on the opposite side. In the causation of hemiplegia, vascular diseases of cerebrum and brainstem exceed all others in frequency. Trauma ranks second, and other important causes are brain tumor, encephalitis or abscess and demyelinating diseases. PMID- 2237065 TI - [Sudden blindness]. AB - Blindness means no light perception. In that case one observes a fixed dilated pupil. An unilateral amaurosis of sudden onset is caused either by an ocular or an optic nerve condition. The most common causes are: --occlusion of the central retinal artery --apoplexy of the papilla --traumatic lesions to the optic nerve Bilateral blindness occurring suddenly is for anatomic reasons due to a chiasmatic lesion. It is mainly associated with pituitary apoplexy. More commonly bilateral blindness develops sequentially and may be discovered only after the second event. Besides other ocular diseases bilateral occipital brain infarction has to be considered. PMID- 2237066 TI - [Physiological aspects of pain in high voltage therapy application in physiotherapy]. AB - Treatment of pain in the locomotor system is one important goal of physiotherapy. To suit this need electrotherapy provides different approaches. Electric impulses in the range of microseconds and a potential of up to 500 Volts are in use for several years. This article deals preferentially with neurophysiologic aspects on the effects of high-voltage-therapy. They may serve the physician as basis for a more conscious selection of indications. PMID- 2237067 TI - [A case from practice (193). Eosinophilia in Enterobius vermicularis infestation. Central hemorrhagic chorioretinopathy of the left eye]. PMID- 2237069 TI - [The value of isometric exercise in patients with coronary disease]. PMID- 2237068 TI - [A case from practice (194). Relapsing fever]. PMID- 2237070 TI - [Silent myocardial ischemia in the diabetic patient]. PMID- 2237072 TI - [Leiomyosarcoma of the small intestine: apropos of 3 case reports]. PMID- 2237071 TI - [Preventive and therapeutic management of diabetic patients, a report of failure?]. PMID- 2237073 TI - [Bursitis of the iliopsoas: an unrecognized cause of leg pain]. PMID- 2237074 TI - [Rheumatism and Crohn's disease. Apropos of 3 cases of preceding arthropathy]. PMID- 2237075 TI - [Postpartum hemorrhage: hazard... or linkage?]. PMID- 2237076 TI - [Endometrial adenocarcinoma and polycystic ovary syndrome]. PMID- 2237077 TI - [A case of Asian rachitis]. PMID- 2237078 TI - [A model of socio-professional rehabilitation of psychiatric patients]. PMID- 2237079 TI - [Management for psychotic patients and drug addicts in a community environment from the psychoanalytic viewpoint]. PMID- 2237080 TI - [The treatment of alcoholism in a general hospital. Experience of an alcoholism unit]. PMID- 2237082 TI - [Urodynamic studies in the incontinent woman in a peripheral hospital: a challenge?]. PMID- 2237081 TI - [Alcoholism: is there a rational explanation for and a specific treatment of the alcohol-dependent patient?]. PMID- 2237083 TI - Thoracic neoplasms. PMID- 2237084 TI - Adjuvant treatment in resected lung cancer. AB - There have been many attempts to develop effective postoperative adjuvant therapy in patients with resected lung cancer. Metastatic disease is the commonest site of first recurrence. In squamous cell carcinoma local failure is another major problem and in adenocarcinoma brain metastases are frequent. There is evidence to suggest that radiotherapy can prevent local recurrence but does not appear to impact on survival. Response rates to chemotherapy alone and chemo-radiotherapy with prolongation of disease-free survival have been encouraging in locally advanced (resected stage II, III) disease when treated postoperatively. Results of clinical trials using immunotherapy or chemotherapy in early stage disease have been disappointing. Several prospective randomized studies by the Lung Cancer Study Group were undertaken to assess the merits of various adjuvant treatments and are presented. PMID- 2237085 TI - Neoadjuvant chemotherapy and surgery of cancer of the esophagus. AB - Neoadjuvant, or pre-operative, chemotherapy for esophageal cancer has become an area of increasing interest because of the failure of conventional therapy (surgery or radiation) to improve disease-free or overall survival. Several autopsy series have demonstrated that, in many symptomatic Western patients, esophageal cancer is a systemic disease. Neoadjuvant chemotherapy thus, in theory, allows a simultaneous attack on both the primary and metastatic disease. A number of single-arm, phase II multi-modality trials have been completed. Toxicities of chemotherapy, while substantial, have been tolerable. With careful attention to detail, operative morbidity and mortality has not been increased. Large-scale randomized trials, needed to evaluate the impact of this technique on disease-free and overall survival, have been designed and will shortly be activated. PMID- 2237086 TI - Adenocarcinoma in Barrett's esophagus. AB - Adenocarcinoma arising in association with the columnar-lined esophagus is now recognized with increasing frequency. The incidence of malignant degeneration in Barrett's esophagus, its etiology, and pathogenesis are all issues of ongoing debate. The role of gastroesophageal reflux in driving the malignant change remains unproven. Surgical resection is the treatment of choice; however, prognosis is generally poor. Surveillance of patients with non-malignant Barrett's esophagus permits detection of early lesions where resection results in excellent long-term survival. PMID- 2237087 TI - Diagnosis and treatment of pleural mesothelioma. AB - Pleural mesotheliomas are uncommon tumors. They can be broadly classified as localized and diffuse. The localized form is a non-epithelial neoplasm that occurs as commonly in women as in men and is not related to asbestos exposure. It is usually asymptomatic, and is occasionally associated with paraneoplastic syndromes. Localized mesotheliomas arise more frequently from the visceral than from the parietal or mediastinal pleura. The long-term outcome of these tumors is determined mainly by their clinical presentation, and by whether or not they can be completely resected. Diffuse pleural mesotheliomas are invariably malignant. They are clearly related to asbestos exposure, and are far more common in men than in women. Histologically, they are completely or partially epithelial tumors. Diffuse mesotheliomas present with dyspnea, chest pain, and weight loss and are not associated with paraneoplastic syndromes. Distinguishing malignant mesothelioma from metastatic adenocarcinoma can be difficult and usually requires a large tissue biopsy on which immunohistochemistry and electron microscopy can be performed. The management of diffuse malignant mesothelioma remains controversial. Treatment appears to prolong survival which ranges from 6 to 12 months with supportive care alone. Surgical resection, either with extrapleural pneumonectomy or by pleurectomy/decortications remains the mainstay of treatment because of the relative ineffectiveness of radiation and chemotherapy. Surgical resection alone, however, is inadequate, so most current treatment regimens combine operation with radiation and/or chemotherapy. Even with aggressive multimodality treatment, the median survival currently ranges from 18 to 24 months. A better understanding of prognostic factors, a better staging system, and innovative treatment strategies are desperately needed in this disease. PMID- 2237088 TI - Management of anterior mediastinal tumors. AB - The most common neoplasms of the anterior mediastinum are thymomas, lymphomas, and germ cell tumors. Surgical exploration was the routine approach to the diagnosis and management of these tumors. This is no longer true. The appropriate initial treatment of these neoplasms varies from surgical resection to radiation therapy to systemic chemotherapy. Except for the small well-encapsulated anterior mediastinal mass, it is imperative that a definitive tissue diagnosis be obtained before initiating treatment. An overview of these tumors and the specific approaches to their treatment are detailed. PMID- 2237089 TI - Prognostic indicators in patients with pulmonary metastases. AB - Pulmonary metastases from different primary neoplasms have different biological characteristics which may correlate with patient survival. Objective criteria to reliably select or exclude patients who would benefit from resection of these metastases are not available; however, various prognostic indicators have been studied for their correlation with post-resection survival. Prognostic indicators differ among various tumor histologies. Prognostic indicators identified preoperatively which may influence post-resection survival include age, sex, histology and location of the primary tumor, tumor doubling time, disease free interval, the number of nodules on preoperative roentgenographic studies, and the number of metastases resected. Following surgery, resectability, and the number of metastases resected may predict expected survival for patients meeting certain criteria. No single criterion should be used to exclude patients from surgery as resection will provide numerous patients with significant post-resection survival. PMID- 2237090 TI - Surgical resection of pulmonary metastases. AB - Since the first pulmonary resection for metastatic carcinoma to lung in 1939, this procedure can now be offered to any patient who fills the following criteria: has a controlled primary, resectable lung lesion, has no better treatment method available, and is a good surgical risk. With the increased incidence of this procedure, more and more attention is being directed to the predictors of survival to determine which patients will obtain the best benefit. Disease-free interval, tumor doubling time, and number of lesions are discussed with the effect each has on survival. This paper covers our experience from 1965 to 1985 of 415 patients who underwent resection for primary carcinomas with metastases to lung. The overall mortality rate is 2%, morbidity rate under 10%, and survival rate best for testicular (51%), and head and neck primaries (47%). This procedure has a proven efficacy for increasing survival rates in properly selected patients. PMID- 2237091 TI - [Functional metabolic neuroimaging by positron-emission tomography in man]. AB - Positron emission tomography allows an in vivo assessment of various physiological and biochemical processes, for example cerebral blood flow, metabolism, or interactions between ligands and receptors. Data quantification and interpretation rest on models describing in a simple way the behavior of the labelled molecules. The general principles are common, but each model has limitations. The different methods are first validated in and applied to normal populations under resting conditions. New techniques for rapid assessments of blood flow and metabolism make it possible to measure cerebral activation after sensori-motor, mental or pharmacological stimulation. This should allow the study of recovery or plasticity of the lesioned brain, after a stroke for example. PET measurements of cerebral blood flow, oxygen consumption and extraction, and cerebral blood volume are particularly well suited to investigate the physiopathology of cerebrovascular diseases. Remote metabolic disturbances give information on interregional cerebral connections, and on clinico-metabolic correlations. In epilepsy, PET is useful in localizing the epileptogenic focus in partial epilepsy: it is hypometabolic interictally. The meaning of the hypometabolism has still to be established. New information about the neurochemistry of the epileptogenic focus should become available from studies of benzodiazepine, excitatory amino acid or opiate systems, for example. PET has already enabled pathophysiological hypotheses to be tested in status epilepticus. Disturbances of metabolism and neurotransmission systems have been observed at various stages and in various types of neurodegenerative diseases. The modifications are not only an early reflection of anatomopathological lesions, but could give more direct information on the pathogenesis or symptomatology of these diseases and hence lead to new therapeutic endeavours, such as appropriate replacement therapy analogous by to dopatherapy in Parkinson's disease. PMID- 2237092 TI - [Spontaneous cerebellar hematoma in adults. 44 cases]. AB - Spontaneous cerebellar hematomas account for 10 p. 100 of all spontaneous intra cranial hemorrhages. In this series of 44 cases, 3 clinico-pathological groups are described on the basis of clinical and pathological data (small, middle and massive hematomas). The mortality rate was high (50 p. 100). Nevertheless, early and direct draining of the hematomas provides the best chances of survival. PMID- 2237093 TI - [Cerebellar ataxia and unilateral asterixis caused by thalamic hematoma. Presumed mechanisms]. AB - A 76 year-old hypertensive man developed an acute inability to stand due to a right cerebellar ataxia. Somatosensory performances were normal, but a transient and mild weakness of the right arm and leg with Babinski's sign was observed. There was a prominent asterixis of the right hand. CT scan showed a hemorrhage of the thalamus with surrounding edema of the adjacent internal capsule. Initial median nerve somatosensory evoked potentials showed a mild reduction of left parietal responses with absent left frontal SEPs (P22 and N30). Fourty days later the cerebellar ataxia was persisting while asterixis had disappeared. A second recording of SEPs showed a complete recovery of all cortical components. MRI performed at the same time showed a left postero lateral thalamic lesion. CT, MRI and SEPs findings suggested that asterixis could result from interruption of somatosensory fibres projecting to the motor cortex. PMID- 2237094 TI - [Standardization of a modular and hierarchic cognitive evaluation scale applicable to dementia. A French version of the Hierarchic Dementia Scale]. AB - We tested a revised version of the Hierarchic Dementia Scale (HDS), proposed by Cole and Dastoor (1980), in order to improve its clinical usefulness and to enrich our knowledge about ageing. The scale was built with 20 subtests which covered the entire range of cognitive and motor functions. Each subtest was hierarchically organized so that success in a item implied success in inferior items. This hierarchical principle was time-saving and was validated by Cole and Dastoor. 149 control subjects performed this test. They were equally divided in 4 age-groups (55-64, 65-74, 75-84, 85-97) and 2 educational levels. None of these subjects had previous history of somatic or neuropsychiatric disease. They were completely self-sufficient in daily life. A large part of the controls failed in the most difficult items of some subtests: Learning, Calculation, Mental Control, Drawing, Recall, Similarities, Constructional Praxis. For these subtests, significantly different mean-scores were observed between age-groups and educational levels. However, the influence of each factor was variable from one subtest to another. Moreover, subgroups seem to exist in our population according to specific difficulties in some of these subtests. This study calls for caution in the interpretation of results in demented patients. Comparisons with other psychometric tools remain to be performed. This scale seems to be more useful for the quantification and follow-up of cognitive deficits than for the early diagnosis of dementia. In addition, this scale, which briefly explores many aspects of cognitive functions, seems especially useful to approach the heterogeneity of DAT. PMID- 2237095 TI - [Intradural extramedullary neuro-enteric cysts without associated malformation. 3 cases with magnetic resonance imaging]. AB - We report 3 cases of extramedullary neurenteric cyst without associated dysraphic lesions. One of the cases had an ultrastructural study. Magnetic resonance imaging provided a preoperative diagnosis. The embryogenesis of neurenteric cysts, their main clinical aspects and their surgical treatment are reviewed. PMID- 2237096 TI - [Neurological disorders disclosing auricular myxoma: 3 cases]. AB - We report 2 cases (n. 1 and 2) of cerebral infarction caused by a left atrial myxoma, and 1 case (n. 3). of dementia associated with a large left atrial myxoma. Cerebral emboli and neurological symptoms which can occur prior to cardiac obstructive and/or systemic signs require echocardiography. The cardiac post-operative condition was dramatically improved in cases revealed by an hemiplegia. PMID- 2237098 TI - [Intracerebral cavernous angioma and transient ischemic complications]. AB - A patient with capsulo-lenticular cavernous angioma presented with transient hemiparetic attacks. A diagnosis of transient ischemic attacks has been accepted and a platelet thrombo-embolic mechanism is suggested. PMID- 2237097 TI - [Meningoencephalitis caused by Coxiella burnetii]. AB - Meningoencephalitis caused by Coxiella burnetii is exceptional and its clinical presentation is varied. We report a case which presented as transient central neurological deficits and intracranial hypertension without fever. The condition was diagnosed by indirect immunofluorescence. PMID- 2237099 TI - [Protracted recurrent neuroleptic malignant syndrome]. AB - The natural course of untreated neuroleptic malignant syndrome (NMS) does not usually exceed 3 weeks. Its duration is reduced by dantrolene and/or bromocriptine. We report a patient in whom NMS developed after an injection of haloperidol decanoate and fluctuated during 3 months. This was due perhaps because the initial treatment with oral neuroleptic was pursued, or because the doses of dantrolene were insufficient. PMID- 2237100 TI - [Oculo-palatal myoclonus and multiple sclerosis]. AB - A 33 year-old woman with multiple sclerosis developed bilateral palatal myoclonus. Rotatory pendular nystagmus and gaze-evoked nystagmus were present and analyzed by electro-oculographic recordings. Magnetic resonance imaging demonstrated abnormal signals in the pons. To our knowledge, this is the first report of palatal myoclonus in the course of a definite case of multiple sclerosis. PMID- 2237101 TI - [Conference at the Salpetriere. January 1989. Progressive paralysis of phonation and deglutition in a 22-year-old man]. PMID- 2237102 TI - [Early diagnosis of cancers of the mouth]. AB - Oral cancers are frequent among men aged 45-60. They are detected by dentists stomatologists and general practitioners, at advanced stages with cervical metastasis node. The routine oral examination and detection of a precancerous lesion or an early cancer for alcohol drinkers are tobacco smokers. Main cancer symptoms are presented there to support diagnosis. PMID- 2237103 TI - [Choice of sectional planes and advantages of the scanner in implantology]. AB - The future site of the implant, close anatomical obstacles and the insertion axis of single various implants, can be determined by the use of the scanner. Giving precise instructions is very important in determining the selection of sectional planes to be used the radiologist such as: axial sections, direct or reconstructed frontal sections, sagittal or reconstructed sagittal oblique sections. Precise measures can be directly realized on the scanner. When it is impossible to obtain the orthogonality of all the sectional planes, correction of the measures can be realized by using the cosinus of the angle obtained by the effective sectional plane and the ideal plane. PMID- 2237105 TI - [Histological aspects of tooth bleaching technics]. AB - The chemical principles of tooth bleaching are detailed in order to analyze scanning microscopy data obtained following internal and external bleaching tooth bleaching appears harmless to the enamel structure providing no etching is applied prior to bleaching. Previous enamel undermining appears to increase the porosity along preexisting cracks. Internal bleaching gives way to enamel and dentinal demineralization, which is of particular importance at the dento enamel junction. The biological effects of bleaching on dental hard tissues must be viewed in light of the clinical indications for these procedures. PMID- 2237104 TI - [Paresthesia of the inferior dental nerve: clinical signs, etiological diagnosis and prognosis 1]. AB - This article is about the different iatrogenic (or others) mechanical and/or chemical trauma that can affect the mandibular nerve and which can lead to paresthesia. Depending on the different causes of the paresthesia, the prognosis for nerve sensitivity regeneration will vary: In some cases treatment is necessary to make the symptoms disappear, in others expectation will be the rull and the prognosis is very poor. PMID- 2237107 TI - [Ex-vivo study of the capacity of bacteria of the genus Capnocytophaga to adhere to human buccal epithelial cells]. AB - The bacteria of the genre Capnocytophaga are part of the subdominant flora of the oral cavity. For diverse microorganisms it has been proved that the adhesion constitutes the first step of the colonization of a place leading to the eventual pathology. The adhesion capacity to human epithelial cells (keratinised and non) of eight strains of genus Capnocytophaga has been studied. All strains appear to have a very weak capacity of adhesion. This diministe can be originated from the fact that the host cells have been harvested from healthy subjects. PMID- 2237106 TI - [Canal Finder System 89!!! Improvements and indications after 4 years of experimentation and use]. AB - Actually, the CANAL FINDER SYSTEM is the only entirely automated endodontic device. After four years of existence, many evaluations were able to show the qualities of this system regarding root canal penetration, cleaning and shaping. The earlier concerns such as ergonomical problems were solved: automated extraction of the K-file, automated sodium hypochlorite irrigation. A new file was created, particularly well adapted to the root canal shaping of curved canals. This addition has improved the efficiency of the automated instrumentation. The CANAL FINDER SYSTEM has reached a maturity level permitting an excellent reliability and ease of use. PMID- 2237108 TI - [Influence of age of the periodontal status of adult diabetics: clinical study]. AB - 340 adult diabetics participated to this work in Conception's Hospital of Marseille. The examinated teeth were the 16, 21, 24, 36, 41 and 44. The indexes (Pl.I., G.I.), the depths of the pockets (upon these teeth), the quantity of gingival fluid (upon 21 and 24 only) were registrated. Statistically, the results showed: the gingival inflammation, the quantity of plaque and the severity of the periodontal disease increase with age and that with a maximum between 55 and 65 years. PMID- 2237109 TI - Bacterial tracheitis: report of eight new cases and review. AB - Bacterial tracheitis, previously referred to as nondiphtheritic laryngitis with marked exudate, was commonly discussed in pediatric textbooks before 1940. It seemed to disappear as a clinical entity after that time, but it has been recorded with increasing frequency in the pediatric literature since 1979. We describe eight new cases and review 110 previously described cases. The clinical course consists of a prodromal upper respiratory illness with stridor, fever, and a variable degree of respiratory distress. Unlike patients with croup, patients with bacterial tracheitis do not respond to aerosolized racemic epinephrine. Most patients require endotracheal intubation; some require tracheostomy. Reported complications include pneumonia, pneumothorax, formation of pseudomembranes, toxic shock syndrome, and cardiopulmonary arrest. Bacterial tracheitis is a secondary bacterial infection following a primary viral respiratory infection. The most common preceding viral infection is parainfluenza. Staphylococcus aureus and Haemophilus influenzae are the predominant causes of bacterial tracheitis. Secondary bacterial infection may occur as a result of tracheal mucosal injury or impairment of normal phagocytic function due to viral infection. PMID- 2237110 TI - Hypercalcitoninemia, hypocalcemia, and toxic shock syndrome. AB - Toxic shock syndrome is a multisystem illness frequently complicated by hypocalcemia. The etiology of the hypocalcemia, which may be severe, is not well understood. We report two cases of fatal toxic shock syndrome accompanied by severe hypocalcemia; each patient also had an inappropriately elevated serum calcitonin level, which in one case was as high as 179,000 pg/mL. Hypercalcitoninemia may be a cause of the low serum calcium levels as well as of certain clinical manifestations of toxic shock syndrome. PMID- 2237112 TI - Acute respiratory disease in Spain: seven years of experience. AB - The clinical and epidemiologic features of viral and nonviral pathogens involved in acute respiratory diseases are described in the context of cases of infection (especially atypical pneumonia and bronchiolitis) studied at the Centro Nacional de Microbiologia, Virologia e Immunologia Sanitarias in Madrid during a 7-year period (1979-1986). These etiologies were demonstrated in 1,637 (36.2%) of 4,521 cases. Among viruses, respiratory syncytial virus most frequently infected children; influenza virus showed the same pattern of circulation as in other European countries. Of nonviral agents, Mycoplasma pneumoniae and C. burnetii were most often involved in lower respiratory tract infections, with a variable predominance in patients of different ages. A high proportion of cases of M. pneumoniae infection occurred in infants and children aged less than 1 year, and most of these cases occurred during spring and summer. The majority of Q fever cases, including those observed in two outbreaks, occurred in the northern region. PMID- 2237111 TI - Brucella endocarditis: the role of combined medical and surgical treatment. AB - Brucella endocarditis, although a rare complication of brucellosis, is the main cause of death related to this disease. This report describes a case of aortic endocarditis due to Brucella abortus in an elderly farmer with known aortic stenosis. Urgent valve replacement was performed because of progressive heart failure despite appropriate antimicrobial treatment. The infection was cured with trimethoprim-sulfamethoxazole and rifampin given for 3 months after surgery. A review of the literature reports on the 38 other cases of cured brucella endocarditis made clear the need for combined antimicrobial treatment and surgical valve replacement. PMID- 2237113 TI - Tuberculous psoas muscle abscess following chemoprophylaxis with isoniazid in a patient with human immunodeficiency virus infection. AB - A 34-year-old man with human immunodeficiency virus infection and disseminated Mycobacterium avium and Mycobacterium intracellulare infection developed a right psoas muscle abscess due to Mycobacterium tuberculosis. The abscess occurred 18 months after completion of a 12-month course of chemoprophylaxis with isoniazid that was given because of a positive reaction with purified protein derivative of tuberculin. The adjacent vertebrae did not appear to be involved. The abscess was drained with a percutaneously inserted catheter, and he received standard antituberculous chemotherapy. Three weeks into therapy, a second drainage with a catheter was required. The isolation of two mycobacteria in this patient and the apparent failure of chemoprophylaxis with isoniazid are noted. PMID- 2237114 TI - Resolution of lung abscess due to Pseudomonas aeruginosa with oral ciprofloxacin: case report. AB - A case of lung abscess due to Pseudomonas aeruginosa is presented that did not resolve with the use of conventional antipseudomonal antibiotics, including tobramycin with ticarcillin-clavulanate and ceftazidime with gentamicin and ticarcillin-clavulanate. Oral ciprofloxacin was administered for 12 weeks, and the infection was resolved. No resistance occurred, and there was no recurrence of abscess within 18 months following therapy. PMID- 2237115 TI - Pulmonary and disseminated infection due to Mycobacterium kansasii: a decade of experience. AB - Fifty-five patients with Mycobacterium kansasii isolates (47 pulmonary and eight disseminated) were identified at a large Texas hospital from 1975 to 1985. The mean age of patients was 60 years, and there was a slight male predominance. Isolation of M. kansasii usually represented disease. The great majority of patients with pulmonary infection due to M. kansasii had underlying pulmonary diseases, and 70% had nonpulmonary predisposing factors. M. kansasii pulmonary disease clinically and radiographically resembled pulmonary tuberculosis. Disseminated M. kansasii infection occurred in severely immunocompromised patients, who frequently had pulmonary predispositions as well. Disseminated infection most of ten involved the lung, reticuloendothelial system, bone, joint, and skin and presented with signs and symptoms related to these organs. Despite only moderate in vitro susceptibility of M. kansasii to routine antituberculous drugs, most patients responded to rifampin-containing regimens. The prognosis of patients with M. kansasii disease was determined primarily by their underlying diseases. PMID- 2237116 TI - Spectrum of Cryptococcus neoformans infection in 68 patients infected with human immunodeficiency virus. AB - Sixty-eight patients infected with human immunodeficiency virus (HIV) and Cryptococcus neoformans who presented to three major medical centers in New Orleans, Louisiana, were studied retrospectively. In patients with meningitis the most common presenting symptoms were fever and headache. Those without central nervous system involvement generally had an isolated pulmonary infection due to C. neoformans and presented with cough and dyspnea. CSF parameters were abnormal in 41% of patients, and the India ink preparation was positive in 88% of patients with cultures of CSF positive for C. neoformans. The overall median survival time for the 47 patients who died was 5 months, with a range of 0-22 months. Of the 27 patients who received maintenance therapy with amphotericin B, two (7%) relapsed. The only factors found to be associated with a poor prognosis were abnormal computed tomography of the head and altered mental status on presentation. C. neoformans infections in HIV-infected patients remain difficult to treat and have a poor prognosis. PMID- 2237117 TI - Comparison of species distribution and antimicrobial susceptibility of aerobic actinomycetes from clinical specimens. AB - To compare the species distribution and antimicrobial susceptibility of aerobic actinomycetes, we evaluated 366 isolates referred to the Centers for Disease Control from October 1985 through February 1988. We used conventional biochemical tests to identify the various species. Four species accounted for 191 (52%) of aerobic actinomycete isolates: Nocardia asteroides (98 isolates), Actinomadura madurae (42 isolates), Streptomyces griseus (28 isolates), and Nocardia brasiliensis (23 isolates). Sputum and wounds were the most common sources. No isolate was resistant to amikacin, no N. brasiliensis isolate was resistant to sulfamethoxazole or trimethoprim-sulfamethoxazole, and no A. madurae isolate was resistant to ceftriaxone or imipenem. In summary, our findings show that unusual species of aerobic actinomycetes can cause infection, colonization, or both and that antimicrobial resistance varies markedly by species. PMID- 2237118 TI - Early treatment with acyclovir for varicella pneumonia in otherwise healthy adults: retrospective controlled study and review. AB - The effect of early acyclovir therapy on the course of varicella pneumonia in previously healthy adults was assessed. Medical records from five university affiliated medical centers were retrospectively reviewed; included were all immunocompetent adults with a clinical diagnosis of primary varicella, a chest radiograph consistent with varicella pneumonia, and an arterial blood gas measurement indicating significant hypoxia. Of the 38 patients who met the study criteria, 11 had had a course of intravenous acyclovir initiated within the first 36 hours of hospitalization; the mean time from admission to initiation of therapy in this early-treatment group was 9.6 hours. The group that received early acyclovir treatment had a lower mean temperature beginning on the fifth day of hospitalization (37.0 degrees C vs. 37.7 degrees C; P = .011) and a lower mean respiratory rate beginning on the sixth day of hospitalization (21 vs. 28 respirations per minute; P = .004). Early acyclovir therapy also resulted in a significant improvement in oxygenation beginning on the sixth day of hospitalization in patients with follow-up arterial blood gas measurements (P = .035). Thus, early institution of acyclovir therapy is associated with reduction in fever and tachypnea and improvement in oxygenation in otherwise healthy adults with varicella pneumonia. PMID- 2237119 TI - Pneumococcal endometritis and neonatal sepsis. AB - A recent case of postpartum maternal endometritis and neonatal sepsis due to Streptococcus pneumoniae prompted this report and a review of previous citations. Although this rare presentation of pneumococcal infection is potentially fatal to both mother and child, early empiric antibiotic coverage for the most frequent etiologic agents of this syndrome, group B streptococci, was and is adequate for systemic pneumococcal infections. PMID- 2237120 TI - Visceral protothecosis mimicking sclerosing cholangitis in an immunocompetent host: successful antifungal therapy. AB - A healthy 39-year-old man who had clinical findings consistent with sclerosing cholangitis was found to have systemic protothecosis at surgery. Severe granulomatous inflammation and palpable nodules were found in the gallbladder, on the surface of the liver, and in the duodenum. Prototheca wickerhamii was detected in biopsied specimens and stool; the titer of indirect fluorescent antibody to this organism was 1:2,000. The patient recovered after a short course of treatment with amphotericin B and 3 months of oral therapy with ketoconazole. He had no other concurrent illness and had no abnormality in his immune system. This is the second reported human case of systemic protothecosis. An elevated IgG level, an elevated erythrocyte sedimentation rate, eosinophilia, and abnormal levels of enzymes in the liver were found in both cases. Protothecosis should be considered in the differential diagnosis of hepatic and biliary inflammatory diseases of uncertain etiology. PMID- 2237121 TI - Enterobacter bacteremia in pediatric patients. AB - Enterobacter has emerged as an important human pathogen, particularly in sick, hospitalized patients. Previous reports of nonepidemic enterobacter bacteremia have focused on adult patients. In this report, the epidemiologic factors, clinical characteristics, treatment, and outcome for 33 patients with enterobacter bacteremia in a large children's hospital during a 5-year period are reviewed. The ratio of males to females was 1.2:1. The patients' ages ranged from 2 days to 24 years, and 18 patients were less than 18 months old. Twenty-two cases were nosocomially acquired; six were polymicrobial in nature. Significantly underlying conditions were present in 32 patients. The biliary tract and central venous catheters were the most common sources of bacteremia. Two-thirds of patients had preceding antibiotic therapy. The overall mortality was 24%; mortality attributable to enterobacter bacteremia was 18%. Statistically significant differences in mortality were associated with an age less than 18 months (P = .031) or thrombocytopenia (P = .017); presence of fever was of borderline significance (P = .098). Enterobacter bacteremia is an important cause of morbidity and mortality in pediatric patients. PMID- 2237122 TI - Postoperative pancreatic abscess due to Plesiomonas shigelloides. AB - Plesiomonas shigelloides is being recognized with increasing frequency as a human pathogen. The organism is ubiquitous in fresh and brackish water, and clinical illness has been associated with foreign travel and ingestion of inadequately cooked seafood. We describe a 64-year-old Filipino woman who presented 2 weeks after elective cholecystectomy and pancreatic biopsy with left upper quadrant pain, abdominal distention, and fever. Computerized tomography of the abdomen revealed an abscess in the tail of the pancreas with fluid accumulation in the lesser omental sac. Percutaneous aspiration yielded purulent material, and P. shigelloides was recovered in pure culture. To our knowledge, this is the first reported case of pancreatic abscess due to P. shigelloides. PMID- 2237123 TI - Endocarditis due to ampicillin-resistant nontyphoid Salmonella: cure with a third generation cephalosporin. AB - A case of ampicillin-resistant salmonella bacteremia complicated by endocarditis in a 78-year-old man is presented. Previous rheumatic valvular heart disease and the lack of response to initial treatment with chloramphenicol prompted us to consider this diagnosis. There was a good clinical response after treatment with ceftriaxone alone and corresponding improvement on the echocardiogram. This case demonstrates the possible endovascular complications of salmonella bacteremia in elderly people and that endocarditis should be included among the invasive infections due to ampicillin-resistant Salmonella that could potentially be treated with the newer cephalosporins. PMID- 2237124 TI - Listerial myocarditis in cardiac transplantation. AB - Clinical signs of heart failure developed in two cardiac transplant recipients and were interpreted initially as graft rejection. Morphologic examination of explanted hearts revealed myocarditis with abscess formation and necrosis consistent with a bacterial process; Listeria monocytogenes was isolated from myocardial tissue in the first case and from blood in both. The first patient also developed signs of meningoencephalitis, but the second had no signs of infection outside the heart. Antimicrobial therapy and retransplantation were successful in eradicating listeriosis. The differential diagnosis of heart failure in cardiac transplant recipients includes infectious myocarditis due to L. monocytogenes. PMID- 2237125 TI - Pneumonia due to Legionella micdadei in bone marrow transplant recipients. AB - Legionella micdadei has previously been described as a cause of nosocomial pneumonia, particularly in kidney transplant recipients. Cell-mediated immunity is the principal host defense against this pathogen. A common clinical scenario in the immunocompromised host is that of septic pulmonary embolus, but asymptomatic infections have also been reported. The organism is weakly acid-fast in clinical specimens but loses this property when grown on solid media. We report two cases of L. micdadei pneumonia, differing markedly in clinical severity and outcome, in bone marrow transplant recipients. Additionally, we note the growth of the organism in liquid culture media with preservation of its acid fast property. PMID- 2237126 TI - Group C streptococcal arthritis: case report and review. AB - Streptococci account for approximately 15%-20% of cases of nongonococcal septic arthritis. The majority of these are due to group A streptococci, but group B and group G streptococci are being isolated more frequently. We present a case of group C streptococcal arthritis and summarize nine additional cases reported in the literature. The group C streptococci include the large colony of Voges Proskauer-negative bacteria (Streptococcus equi, Streptococcus equisimilis, Streptococcus zooepidemicus, and Streptococcus dysgalactiae) as well as as the minute colony of Voges-Proskauer-positive Streptococcus anginosus ("Streptococcus milleri") group C organisms. Any joint may become infected, but joints affected by preexisting rheumatologic abnormalities are more frequently involved. Bacteremia was documented in five of the 10 patients. One patient had an associated pneumonia, and another patient had an associated acute aortic valve endocarditis. None of the infections involved a prosthetic joint or an overlying cellulitis, associations reported for group G streptococcal arthritis. Surgical drainage of the infected joint was required in six of the 10 patients. We concluded that the presence of two groups of organisms sharing the same Lancefield group antigen necessitates the careful identification of isolates to determine potential clinical differences. PMID- 2237127 TI - Primary meningococcal conjunctivitis: report of 21 patients and review. AB - Neisseria meningitidis is an uncommon cause of acute bacterial conjunctivitis. Twenty-one cases of primary meningococcal conjunctivitis (PMC) are reported herein and 63 cases published in the literature since 1899 are reviewed. In the 84 cases of PMC available for analysis, the male-to-female ratio was 1.76:1; nine of the patients were neonates, 55 were children, and 20 were adults. Conjunctivitis was unilateral in 66.3% of the patients. Gram stain of conjunctival exudate disclosed gram-negative diplococci in all cases in which it was done. Culture of the conjunctival exudate yielded N. meningitidis in all cases, and 44% of the isolated meningococci belonged to serogroup B. Ocular complications, which occurred in 15.5% of the patients, most frequently were corneal ulcers. Systemic meningococcal disease developed in 17.8% of the patients; the overall mortality was 13.3% for patients with PMC complicated by systemic disease. Development of systemic disease was significantly more frequent in patients receiving only topical therapy than in those treated with systemic therapy (31.71% vs. 2.38%; P = .001). Gram-negative diplococci observed in conjunctival exudate are an indication for systemic antibiotic therapy because of the risk of systemic complications associated with the use of topical therapy alone. When properly treated, patients with PMC have a favorable prognosis. PMID- 2237128 TI - Emphysematous gastritis: case report and review. AB - Emphysematous gastritis is a condition involving gastric wall inflammation, radiologic or intraoperative evidence of intramural gas, and systemic toxicity. A recent case of emphysematous gastritis in a 57-year-old diabetic man is reported, and 27 cases published since 1889 are reviewed. Predisposing factors include ingestion of corrosive substances (37%) and alcohol abuse (22%). Diagnosis of emphysematous gastritis is based on the clinical presentation of an acute abdomen with systemic toxicity and on radiographs demonstrating gas bubbles within the stomach wall. For the case reported herein, computed tomography was useful both in establishing the diagnosis and in following the resolution of emphysematous gastritis. Organisms most commonly involved were Escherichia coli (six cases), Streptococcus species (six cases), Enterobacter species (five cases), and Pseudomonas aeruginosa (three cases). The mortality was 61% (17 of 28 patients), and morbidity with gastric contractures occurred in 21% of cases (6 of 28). Optimal therapy has not been defined; however, antimicrobial chemotherapy and surgery, when appropriate, may improve survival rates. PMID- 2237129 TI - Emerging role of lactobacilli in the control and maintenance of the vaginal bacterial microflora. AB - The vaginal microflora of healthy asymptomatic women consists of a wide variety (two to five isolates at any one time) of anaerobic and aerobic bacterial genera and species dominated by the facultative, microaerophilic, anaerobic genus Lactobacillus. That the vaginal flora forms part of a dynamically changing ecosystem is evident from the variable prevalence and population levels of each bacterial species detected with repetitive longitudinal sampling, with pregnancy, and with stage in the menstrual cycle. This review emphasizes the role that vaginal lactobacilli may play in control of the vaginal microflora and maintenance of the normal state. Lactobacilli possess many antagonistic properties and produce many metabolites that may be important in maintaining dominance in the vagina. Contradictory data from previous studies regarding the impact of factors such as contraception, catamenial products, and physiologic elements on the vaginal microflora are due in part to poor study design and differences in methodology. Well-designed and controlled investigations with large numbers of individuals in each group are needed, and the limitations of the methodology for such investigations must be considered. Studies of the normal flora, exploring the interaction of lactobacilli and other bacterial species, must be performed before the pathologic processes resulting in vaginitis or systemic sequelae are investigated. PMID- 2237130 TI - Quinolone antibiotics in the treatment of Salmonella infections. AB - The 4-fluoroquinolones are a new class of antimicrobial agents that possess broad in vitro antibacterial activity, including efficacy against enteric pathogens such as Salmonella, Shigella, Campylobacter, Yersinia, and Vibrio species. These drugs are clinically effective against both drug-sensitive and multiresistant strains of Salmonella typhi and Salmonella paratyphi that cause enteric fever. In salmonella enterocolitis, the quinolones--unlike older antimicrobial agents that may have little impact on the duration of symptomatic illness and can in fact prolong fecal carriage of salmonellae--actually shorten the course of clinical disease and terminate excretion of these organisms in the stool. Similarly, for chronic carriers of both typhoidal and nontyphoidal Salmonella strains, the quinolones are effective in eradicating biliary and fecal reservoirs of infection. Immunosuppressed persons with salmonellosis, such as those with AIDS, may benefit from both short-term treatment and prolonged prophylaxis with a quinolone antibiotic. The optimal agent, dose, and duration of quinolone therapy for all salmonella syndromes remain to be determined by larger controlled trials. PMID- 2237131 TI - Infectious diseases as a Canadian subspecialty, with projections to the year 2000. AB - Infectious diseases is a relatively new subspecialty in Canada. During the past decade, however, important advances have been made. These include the formation of the Canadian Infectious Diseases Society and the development of the first Royal College of Physicians and Surgeons examinations in the subspecialty of infectious diseases. The majority of Canadians training for practice in the field of infectious diseases are now enrolled in programs in Canada. Despite predictions in the United States of an excess of physicians who specialize in infectious diseases, such a situation has not occurred in Canada. More physicians with training in infectious diseases will be required in Canada in the next decade to fill positions in patient care, microbiology (for individuals with both clinical and laboratory training), research, epidemiology and infection control, programs related to human immunodeficiency virus infections, geographic and international medicine, the pharmaceutical industry, and education and administration. In Canada, the extent to which infectious diseases physicians are involved in these areas varies from that in the United States. This review suggests a continued need for physicians with appropriate training in infectious diseases. PMID- 2237132 TI - Current advances in the diagnosis and treatment of AIDS: an introduction. AB - Significant progress has been made in the diagnosis and treatment of AIDS. Laboratory tests available for assessment of human immunodeficiency virus (HIV) infection include the detection of antibodies to HIV type 1, the direct detection of the virus, the identification of surrogate markers, and the phenotypic analysis of peripheral blood mononuclear cells. Clinicians have made great strides in the treatment of tumors, opportunistic infections, and complications associated with AIDS as well as in the treatment of the infection itself. In selected patients, treatment with interferon-alpha has been successful against AIDS-related Kaposi's sarcoma. Attempts to treat the leukopenia and anemia of patients with AIDS by the administration of hematopoietic growth factors have resulted in increased white blood cell counts and a decrease in erythrocyte transfusion requirements. In addition to zidovudine, several antiretroviral agents are undergoing testing, including the nucleoside analogues dideoxycytidine and dideoxyinosine, soluble CD4, and the glycosidase inhibitor N butyldeoxynojirimycin. PMID- 2237133 TI - Laboratory methods in the diagnosis and prognostic staging of infection with human immunodeficiency virus type 1. AB - Laboratory evaluation of infection with human immunodeficiency virus type 1 (HIV 1) may involve detection of antibodies to HIV-1, direct detection of HIV-1 itself, and measurement of an individual's immunologic status at the time of presentation. The ELISA is currently the preferred initial screening test, although a variety of other rapid immunoassays have also been developed. Methods defining the antigenic specificity of the antibody response, such as the western blot, have become standard confirmatory tests in this setting. CD4+ cell enumeration and the HIV-1 antigen capture assay are useful in predicting the course of HIV-1 infection and in monitoring antiretroviral therapies. Newer techniques of HIV-1 co-cultivation permit the characterization of viral isolates and the stratification of patients and facilitate monitoring of the effects of antiretroviral agents. The polymerase chain reaction is of value in identifying HIV-1 infection in individuals with inconclusive serologic results. Judicious use of other laboratory tests, including surrogate markers such as beta 2 microglobulin, also provides prognostic information potentially useful in clinical management of HIV-1-infected patients. PMID- 2237134 TI - Management of the hematologic complications of human immunodeficiency virus infection. AB - Replication of various strains of human immunodeficiency virus can be increased in vitro by certain colony-stimulating factors (CSFs), but the protective effect of zidovudine (AZT) on macrophages is not antagonized in the presence of those factors--specifically, in the presence of granulocyte-macrophage CSF (GM-CSF). In clinical studies, GM-CSF given alone dramatically increased counts of white cells, particularly neutrophils and band cells. Very small doses of GM-CSF, self administered subcutaneously, restored white cell production in leukopenic patients with AIDS. Combination treatment with AZT and GM-CSF in AZT-intolerant patients allowed resumption of AZT treatment and increased bone marrow cellularity. Treatment of anemic patients who have AIDS or AIDS-related complex with recombinant human erythropoietin (r-HuEPO) produced promising results. After 12 weeks of treatment with r-HuEPO, the need for transfusions to maintain hematocrit values within the normal range was reduced significantly or eliminated in patients with low baseline levels of endogenous erythropoietin. Studies combining AIDS chemotherapy with CSF or erythropoietin treatment are proposed. PMID- 2237135 TI - Therapeutic approaches to neoplasms in AIDS. AB - The multifactorial etiology of Kaposi's sarcoma (KS), which is seen primarily in men, includes genetic predisposition and immunosuppression. Recently, the KS seen in association with human immunodeficiency virus (HIV) infection has been shown to be mediated by the production of certain growth factors. HIV per se may also play an etiologic role via its tat gene. Therapeutic options include irradiation for local or cosmetic control, interferon-alpha, combinations of antiretroviral agents and interferon-alpha, and chemotherapy. The use of antineoplastic agents, either individually or in combination, in cases of advanced disease has been somewhat successful, but resultant immunosuppression and neutropenia may predispose patients to further infection, thereby adversely affecting survival. AIDS-related lymphoma, a late manifestation of HIV infection, often presents with widespread extranodal disease; the median survival time in all series has been approximately 6 months. Two-thirds of patients may have central nervous system involvement at some time in the course of illness. Intensive chemotherapeutic regimens are associated with an increased likelihood of opportunistic infection and do not prolong survival. Combinations of antineoplastic agents given at low doses for short periods may be associated with long-term remissions. PMID- 2237136 TI - New antiretroviral agents in the clinic. AB - Since the first controlled clinical trial of zidovudine (ACT) was terminated in the fall of 1986, much has been learned concerning the use of this agent in the treatment of human immunodeficiency virus (HIV) infection. The recent report of HIV resistance associated with long-term AZT therapy has accelerated the sense of urgency about the development of additional agents for use--either alone or in combination with AZT--against this infection. Several new agents are in various stages of preclinical or clinical evaluation. Some, such as dideoxycytidine, dideoxyinosine, dideoxydidehydrothymidine, azidouridine, and foscarnet, inhibit viral DNA synthesis through inhibition of reverse transcriptase. Other potentially useful agents presumably act at different stages of infection. Soluble CD4, for example, is a soluble form of the receptor to which HIV must bind to infect cells, and castanospermine represents a new class of compounds that block the maturation process of the viral glycoprotein. An apparently more potent and less toxic analogue of the latter agent, N-butyl-deoxynojirimycin, is currently in phase I testing. PMID- 2237138 TI - Persistent neutrophilic meningitis due to Pseudallescheria boydii. PMID- 2237139 TI - Infections in patients with cancer in Mexico. PMID- 2237137 TI - Measles in Israel, the West Bank, and Gaza: continuing incidence and the case for a new eradication strategy. AB - Measles continues to occur in epidemic waves in Israel, Gaza, and the West Bank, causing morbidity and mortality. In Israel, immunization of infants against measles began in 1967, and 90% had been immunized by the mid-1980s. In Gaza and the West Bank, where immunization of infants against measles began in 1973 and 1976, respectively, the immunization rate reached 75% in the late 1970s and increased to greater than 90% in the 1980s. Measles epidemics, which previously had occurred in 5- to 7-year cycles, occurred every 2-4 years in the 1980s and affected individuals who were older than those affected in previous years. Israel's commitment to eradicating measles by 1992 will require a substantially expanded immunization program in comparison with the traditional program that requires immunization of infants alone. The benefits of several alternative immunization strategies considerably exceed their costs. A new, two-dose immunization will be needed as a minimal strategy, and a campaign for administering booster doses to school-aged children may be required as well to achieve control and eradication of measles. Measles is a serious but preventable public health problem; appropriate strategies must be devised by national and international public health officials to control the disease in developing and developed countries. PMID- 2237140 TI - Disseminated infection due to Mycobacterium fortuitum in a patient with AIDS. PMID- 2237141 TI - Dexamethasone for the treatment of children and adults with bacterial meningitis. PMID- 2237142 TI - Mixed staphylococcal and cryptococcal epidural abscess in a patient with AIDS. PMID- 2237144 TI - [A rare cause of pleurisy from subdiaphragmatic origin: epidermoid cyst of the spleen]. AB - Subdiaphragmatic diseases are a classical but uncommon cause of pleural effusion. We report here the case of a woman admitted for a left pleural effusion which led to the discovery of a splenic tumour. Pathological examination of the splenectomy specimen showed that the tumour was an epidermoid cyst of the spleen. Cysts of the spleen are exceptionally revealed by pleurisy. Epidermoid cysts account for 10% of all non-parasitic splenic cysts. They remain silent for a long time and are usually disclosed by such complications as compression of surrounding organs, rupture or superinfection. PMID- 2237143 TI - [Bronchial tuberculosis. Radiologic endoscopic and clinical aspects]. AB - Nowadays, bronchial tuberculosis is an uncommon, although probably underestimated, form of tuberculosis. The records of 23 patients hospitalized between 1978 and 1989 were reviewed retrospectively. Mean age was 57 years (range: 22 to 84 years). Only one female patient of african origin was a recent immigrant. The disease was pseudo-tumoral in 2 cases and included lymph node fistulae in 4 cases. M. tuberculosis was found at microscopic examination in only 10 patients. The course of the disease was slow and sometimes erratic, even under a well-conducted medical treatment. In one of the female patients, a lymph node fistula appeared after 6 months of chemotherapy, and it is clear that medical treatment must be pursued well beyond the conventional time limits. Several mechanisms are responsible for bronchial tuberculosis: either invasion of the neighbouring bronchi by pulmonary tuberculosis; or lymph node fistula now more frequently due to reactivation of old lesions than to a recent primary infection; or again primary bronchial lesions mimicking bronchial carcinoma. PMID- 2237145 TI - [Demons-Meigs' syndrome. Report of a case with ovarian tumor of the granulosa]. AB - We report an original and atypical case of Meigs' syndrome with bilateral pleural blood effusion and without ascites in a woman with a rare ovarian tumour involving the stratum granulosum. Excision of the tumour rapidly resulted in the pleural effusion drying up. PMID- 2237146 TI - [Cutaneous necrosis at the initiation of antivitamin K treatment disclosing hereditary protein C deficiency]. AB - We report the case of a 57-year old woman whose severe protein C deficiency was revealed soon after oral anticoagulants were introduced into her treatment. Two previous episodes of deep leg vein thrombosis followed by a third episode with suspicion of embolus migration had led to treatment with heparin later replaced by oral anticoagulants. On the 4th day of anticoagulant therapy, she developed skin necrosis of the left calf. A protein C assay showed severe deficiency (19% level as compared with the 70-120% normal levels). The main causes of acquired protein C deficiency were excluded. The first results of a family study demonstrated moderate protein C deficiency in a 30-year old, asymptomatic daughter. PMID- 2237147 TI - [Hepatic toxicity of antitubercular agents: role of the HBS antigen carriers]. PMID- 2237148 TI - [Mediastinal abscess fistulized in the esophagus]. PMID- 2237149 TI - [Consensus conference: pneumocystosis in HIV infections. 1st consensus conference in anti-infection therapeutics organized by "la Societe de Pathologie Infectieuse de langue francaise", May 11, 1990]. PMID- 2237150 TI - [Thoracic actinomycosis. Report of 8 cases]. AB - We report 8 cases of thoracic actinomycosis, a disease which is now uncommon owing to the widespread use of antibiotics and which is caused by anaerobic filamentous bacteria living as saprophytes in natural cavities. Recent pathogenetic data, such as propagation by continuity or blood stream, as well as bacteriological and clinical data (mediastino-pulmonary, pleural, parietal, cardiac and disseminated lesions) are reviewed. Diagnostic problems are due to the difficulties encountered in trying to isolate the saprophytic organism, and pathological examination is often required for the diagnosis. Treatment is basically medical and consists of penicillin G or A administered for prolonged periods. Nitroimidazoles are ineffective against these anaerobic bacteria. PMID- 2237151 TI - [Bronchial cancer in patients infected with human immunodeficiency virus (HIV). Report of 3 cases]. AB - We report 3 cases of bronchial carcinoma in patients with human immunodeficiency virus (HIV) infection. Like the other 13 cases found in the literature, these were characterized by their occurrence in young subjects, their often adenocarcinomatous nature and their abnormally severe course. These clinical features raise the problem of the role played by HIV in the development and, above all, the clinical expression of bronchial carcinoma. PMID- 2237152 TI - [From the anatomy to the technic of vaginal hysterectomy]. AB - The technical difficulties in the vaginal hysterectomy (VH) are principally raised by the special conceptualization of the normal anatomy in the craniocaudal direction and the topographical modifications from the surgical manipulations. These modifications have been studied during an operative dissection on a dead body non-formulated, but with the vessels previously injected with coloured latex. Our observation and the numerous works of per-operative radiology are showing that, at every period of the VH there is an ureterical safety margin much more important than in the abdominal hysterectomy. The prime manipulation in its realization is the caudal and continuous traction of the cervix in order to individualize the ligaments and to make easier the dissections. The operation amounts to three primary stages: breaking away the uterus from its visceral connections in order to hold them distant with valves; releasing the uterus from its ligaments with ligatures spaced from the cervix to the fundus; restituating the peritoneal cavity and the vaginal fornix in its topography and statics. The vaginal hysterectomy has notable advantages in swiftness, absence of intestinal manipulations and scarceness of ureterical injuries. The anatomical limits in the low way, depend on the vaginal compliance, the mobility of the pelvic organs and the disproportion between the vagina and the deferent duct. PMID- 2237153 TI - [What place is given to autopsy in cases of perinatal death?]. AB - The authors studied two series of deaths (437 cases in all), one from a prospective study on the Centre region and the other from a retrospective study on the Tourangelle region; they compared the clinical and paraclinical data recorded during pregnancy, labour and the neonatal period to the autopsy results and those of the different tissue examinations, and strived to define the most judicious indications for autopsies in case of perinatal death. From their conclusions, based on the clinical context of the death, 5 different types of situations can be distinguished: for two of them, namely the medico-legal context and the malformation context, the post mortem examination seems indispensable for different reasons. In case of "obvious clinical diagnosis", the need for an autopsy has not been proven. However, when the clinical diagnosis seems "probable" or when the aetiology has not been found clinically, the post mortem examination of the foetal body is recommended, although certain particular situations, related to the age of the mother, the parity, the interest shown by the couple about the result, to ethnic or religious factors, may lead to the request of only a limited examination, which is much less expensive. PMID- 2237154 TI - [Indications and results of autotransfusion. Normovolemic hemodilution in gynecology-obstetrics]. AB - Considering the importance of haemorrhagic complications in gynaecology obstetrics and the increasing fear of accidents during blood transfusion, the authors propose, from the literature and the study of 13 cases, a reflection on the indications of deferred autotransfusion (DAT) and of normovolemic haemodilution (NVH). In obstetrics, even if DAT has undoubtedly certain advantages (besides viral contaminations, appearance of allo-antibodies...), it can be indicated at present only for pregnant women exposed to a predictable risk of haemorrhage or for women with a rare blood group. In gynaecology, the authors have not found any significant advantages in our study as regards NVH associated with DAT. However, as in obstetrics, the technique is harmless, and no thrombo embolic complications have been observed, even in women at high thrombotic risk. These methods are expensive and require qualified personnel. Their exact modalities and indications, as well as their medico-legal aspects, are yet to be defined. PMID- 2237155 TI - [Diagnostic value of calcifications in mammography]. AB - The authors underline the importance of the mammographic screening of calcifications in the early diagnosis of breast tumours. Most of the time, their semeiology seems to be well codified in benign and malignant lesions, although the "visibility threshold" is still not very satisfactory, even by the valuable xeromammographic method. PMID- 2237156 TI - [Serous tumors of the ovary with limited malignancy. Current analysis of a review of the international literature apropos of a case]. AB - Serous ovarian tumours on malignancy borderline represent 2 to 5% of the epithelial ovarian tumours. They differ from malignant tumours by two particularities, namely: precise histological characteristics, the main one being the absence of stroma invasion, a favourable prognosis. The diagnosis rests on conventional histology in spite of the value of histo-immunoclinical markers or tumoral markers. The treatment is surgical, based on hysterectomy with bilateral adnexectomy, even if a conservative attitude may be considered for the young woman who wishes a pregnancy. Prolonged post-operative surveillance is very important because of possible relapses, whose detection seems to be facilitated by antigen CA 125 assay. PMID- 2237157 TI - [Antithrombin III deficiency and pregnancy. Apropos of a case]. AB - Congenital deficiency of antithrombin III is a disease inherited as an autosomal dominant which predisposes to thromboembolism. Pregnancy and the postpartum period constitute a major additional risk factor for thromboembolism in deficient women. However, pregnancy may be envisaged without risk since there has been an improvement in knowledge concerning the physiology of the AT III molecule, its exact role in coagulation, the application of accurate laboratory tests which measure the deficiency, and especially the programming of pregnancy under cover of preventive treatment consisting of the perfusion of AT III concentrate in association with heparin. The treatment is restricting and costly but is, nevertheless, the only one to recreate conditions that are similar to physiological conditions, and its effect is therefore more certain. PMID- 2237159 TI - [Fetal thoracopagus. Echographic diagnosis at 26 weeks]. AB - The authors report on one case of thoracopagus discovered by echography carried out after 26 weeks of amenorrhoea. The pregnancy was terminated therapeutically by hysterotomy when common viscera were identified (heart and liver). Echographic diagnosis during the first part of pregnancy allows evacuation to be carried out by the vaginal approach. The authors summarize the criteria for echographic diagnosis and also the epidemiological and embryological data required for assessing the prognosis. PMID- 2237158 TI - [Tubo-ovarian actinomycosis]. AB - Pelvic actinomycosis is uncommon and usually represents a complication of an intrauterine device (IUD). This organism is very difficult to culture, and most actinomyces is actually identified by histologic features in pathologic specimens or by cytologic features on Papanicolaou smears. A specific fluorescent antibody stain is also available. Tubo ovarian abscess is usually polymicrobial with a preponderance of anaerobic organisms and the exact role of actinomyces in abscess formation remains unclear. PMID- 2237160 TI - [Veins and hormones: a conflicting couple]. AB - The female reproductive lifetime is marked by a number of disruptions in hormonal conditions (oral contraception, pregnancy, menopause), whose impact on the cardiovascular system is not negligible. The author reviews these different stages and their repercussions on the venous system. PMID- 2237162 TI - [Continuing education]. PMID- 2237161 TI - [The planet in peril]. PMID- 2237163 TI - [The nursing profession in France. F4. Professional continuing education. Functions of the hospitals]. PMID- 2237166 TI - [The need for nursing research and care]. PMID- 2237164 TI - Phenotypic analysis of human peripheral blood lymphocytes by automatic sampling flow cytometry after stimulation with mitogens or allogeneic cells. AB - Human peripheral blood lymphocyte (PBL) phenotypes have been analyzed before and after stimulation with phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PWM) for 3 days and in mixed lymphocyte culture (MLC) for 7 days. PBL labeled with each of 10 fluorescent monoclonal antibodies were automatically sampled for flow cytometry from 96-well microtiter plates using a microsample delivery system. The reference phenotypic ranges were determined in fresh cells and control cultures. PHA was mostly mitogenic for T PBL bearing the CD3, CD5, CD7, CD8 and CD25 differentiation clusters, and a low density of CD1 and CD4 had a small effect on human natural killer cells (HNK) and also did not stimulate B (CD19) and HLA-DR+ PBL. There was an incomplete phenotypic overlapping between PHA- and ConA-stimulated cultures, ConA being more mitogenic for CD4 and less mitogenic for CD8 PBL. The mitogenic effect of PWM was evident on CD3, CD5, CD7, CD4, CD25 and CD8, but not on HNK, HLA-DR and CD19 B PBL, which presumably had already differentiated into antibody-secreting cells. After MLC stimulation all T, B and HNK PBL subsets tested were increased, but the cells bearing CD1, CD4, CD5, CD7, CD25, HNK, CD19 and HLA-DR had the greatest proliferation with respect to the unmixed control PBL. The present approach to the phenotyping of PBL subsets could offer more complete and accurate data for monitoring and follow-up of patients in transplantation and immunopathology hospital wards. PMID- 2237165 TI - [The function of the hospital in overcoming the crisis in medicine]. PMID- 2237167 TI - [Bladder rehabilitation of the spinal cord injury patient]. PMID- 2237168 TI - [Nursing coresponsibility in a health team]. PMID- 2237169 TI - [Sexuality in the elderly. The building of a myth?]. PMID- 2237170 TI - [The diabetic adolescent]. PMID- 2237171 TI - [The quality of life, the quality of care]. PMID- 2237172 TI - [On the food habits and consumption of the elderly. A practical study]. PMID- 2237173 TI - [The peridural catheter]. PMID- 2237174 TI - [The fatigue of waiting]. PMID- 2237175 TI - [Continuing education. 51. Subject: basic nursing. Topic: the nursing care process]. PMID- 2237176 TI - [Radiologic methods in cases of coronary heart disease: diagnostic requirements from the cardiology point of view]. AB - Radiological and especially scintigraphic methods are important tools in diagnosis finding, diagnosis evaluation, risk stratification and therapy control in patients with coronary artery disease. The major task is to document or exclude myocardial perfusion defects. Within this framework, thallium scintigraphy and radionuclide ventriculography occupy a definite place for non invasive evaluation. The decision for revascularisation (bypass surgery, angioplasty) and the evaluation of the risk frequently depends on the results of the scintigraphic methods. Conventional radiological techniques and computer tomography are helpful in differential diagnosis of acute chest pain syndromes. PMID- 2237177 TI - [Cardiac diagnosis in the conventional chest x-ray]. AB - Thoracic x-ray examination supplies information that is important in diagnosing heart disorders. The article presents the pathophysiological fundamentals and x ray morphology criteria for assessing the size of the entire heart and of the individual cavities as well the cardiac functions, in a comprehensive survey. PMID- 2237178 TI - [The assessment of myocardial perfusion using contrast echocardiography]. AB - A brief survey is given on the state of the art of qualitative and quantitative myocardial contrast echocardiography as well as on the contrast agents used. Exact qualitative assessment of coronary perfusion areas is possible. In addition, myocardial areas of collaterals of less than 100 microns in diameter can be visualized and measured that were not seen by routine coronary angiography. Quantitative analysis was done in 5 normal subjects and 16 patients with coronary artery disease before and after right ventricular stimulation (170 bpm over 75 s). While decay half time (T1/2) remained unchanged in normal subjects before and after pacing (7 +/- 4 s vs 7 +/- 5 s), it increased significantly from 5 +/- 1 to 16 +/- 1 s in patients with coronary stenoses between 50% and 75%. Stenotic area reduction greater than 75% had significant prolongations of T 1/2 = 12 +/- 7 s already at rest with further prolongation to 36 +/- 17 s (p less than 0.05) after pacing. Regional wall motion in these areas, however, was not significantly altered either in the fixed axis or floating axis system. Following dipyridamole hyperaemia (0.56 mg/kg i.v.), normal subjects showed a significant shortening of T 1/2 (6 +/- 2 vs 1.6 +/- 1; p less than 0.01; n = 5), while T 1/2 of patients with multiple vessel disease was prolonged from 9 +/- 6 to 15 +/- 6 s (p less than 0.01; n = 7). This prolongation was not uniform, since some myocardial areas were found to be hyperaemic after dipyridamole. One patient showed an opening of antegrade collaterals following dipyridamole. In first results myocardial contrast echocardiography proved capable of recognizing ischaemic and hyperaemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237179 TI - Future perspectives: diagnostic possibilities with positron emission tomography. AB - While evaluation of regional myocardial metabolism for diagnostic purposes is currently confined to ischemic heart disease, the emergence and implementation of new tracer approaches is likely to expand the scope of clinical applications. Evaluation of neuronal control of the heart with tracers of adrenergic neuron densities and beta-adrenergic and cholinergic post-synaptic activity promises to be useful in patients with electrical instability and with cardio-myopathies as well as for verifying responses to therapeutic interventions. The possibility to measure regional oxidative metabolism should further prove useful for distinguishing between residual oxidative and anaerobic metabolism in ischemia and thus prove useful for more accurate characterization of the ischemic injury. The method should further become useful for examining cardiac efficiency and detecting the effect of therapeutic interventions. Lastly, techniques for measurements of protein synthesis are likely to become important for defining myocardial maturation, compensatory adjustments of the myocardium to increased pressure and volume loading as well as assessment of repair processes after injury to myocardium. PMID- 2237180 TI - [Computed tomography and magnetic resonance tomography in cases of coronary heart disease]. AB - MR has replaced CT in cardiology as a tomographic examination method with the exception of the identification and differentiation of cardiac calcifications. MR combines good morphological visualization with function diagnostics and biochemical informations. Both methods are inappropriate for diagnosing diseases of the coronary vessels. PMID- 2237181 TI - [The estimation of blood circulation parameters using imaging techniques- comparison with measurements made using the Swan-Ganz catheter]. AB - Circulation can be evaluated by means of measuring parameters in X-ray-thorax and ultrasonography. Changes in haemodynamics can be estimated by measured changes in width of vena azygos. Additional sonography of systemic veins of thoracic inlet (V. jugularis interna, V. cava inferior) improves multiple correlation to circulating blood volume up to r = 0.81. Supine or erect position and type of ventilation are influencing factors. Diaphragm motility was measured by means of ultrasonography: patients with assisted ventilation showed significantly decreased motility compared to patients with spontaneous breathing. PMID- 2237182 TI - [Acute lupus erythematosus disseminatus in adults: clinical aspects & course]. AB - Acute systemic lupus erythematosus (SLE) is characterized by a variety of manifestations and by the almost constant presence of anti-nuclear antibodies. In order to distinguish it from other systemic diseases, eleven diagnostic criteria have been laid down, four of which at least must be present. In 50 p. 100 of the cases the disease is revealed by a non-destructive inflammatory polyarthritis which is highly suggestive when associated with a "butterfly" facial erythema. The main prognostic criteria are renal lesions and their histological type. Nervous system involvement seems to be less frequent and less severe nowadays, but it may leave sequelae. Pleuropericarditis and vascular thrombosis are commonly part of the clinical set up. Antinuclear antibodies are detected by immunofluorescence in more than 95 p. 100 of the patients, but they are not specific to SLE. Their absence in the initial phase of the disease may throw doubts on the diagnosis. Antibodies to DNA and Sm are more specific but inconstant. SLE is a chronic disease with intermittent flare-ups: 30 p. 100 of the patients may hope for a prolonged complete remission. At present, the survival rate at 10 and 20 years is higher than 80 p. 100 and 70 p. 100 respectively at the cost of a very close supervision but also of iatrogenic complications in increasing numbers. PMID- 2237183 TI - [Chronic lupus erythematosus, subacute cutaneous lupus]. AB - The cutaneous manifestations of lupus erythematosus (LE) are extremely varied, and they predominate among the clinical signs of chronic LE and subacute cutaneous LE. In chronic LE, typical lesions are found in regions exposed to sunlight and consist of erythema, hyperkeratosis and skin atrophy. The skin of patients with subacute cutaneous LE is also highly sensitive to light; the lesions consist of an annular or polycyclic or sometimes psoriasiform erythemato squamous eruption observed mainly in uncovered areas. These dermatological forms are part of the wide spectrum of "lupus". Cutaneous manifestations are often associated with systemic signs of varying type and severity and with immunological abnormalities, such as antibodies to Ro in subacute cutaneous LE, which act as markers of the disease. PMID- 2237184 TI - [Antiphospholipid syndrome]. AB - The antiphospholipid antibody syndrome is characterized by venous and/or arterial thrombosis, repeated miscarriages and the presence of anticardiolipin antibodies and/or a circulating lupus anticoagulant. Antibodies directed against phospholipids constitute a family of immunoglobulins with different specificities. The mechanism through which lesions are induced by these antibodies has not yet been fully determined. Treatment includes immunosuppressive measures and prevention of recurrent thrombosis. PMID- 2237185 TI - [Lupus and protein deficiencies of the classical complement pathway]. AB - Deficiencies in proteins of the classic complement pathway are particularly frequent in patients with autoimmune diseases, notably systemic lupus erythematosus (SLE). The C4 component is a polymorphous glucoprotein coded by two closely linked genes, C4A and C4B, located within the HLA complex. C4, and in particular the C4A isotype plays a major role in maintaining immune complexes in solution. Fifty percent of patients with SLE are homozygous or heterozygous to the silent allele C4 AQO. Hereditary CE deficiency is often complicated by lupus related diseases which may be associated with repeated infections. The biological particularity of SLE associated with complement protein deficiencies is the frequency of anti-SSA (Ro) antibodies. PMID- 2237186 TI - [Iatrogenic lupus]. AB - Drug-related lupus accounts for about 10 p. 100 of all lupoid diseases. The main responsible drugs are antihypertensive, antiarrhythmic and anticonvulsant agents, phenothiazines and beta-blockers. Iatrogenic lupus has a better prognosis than idiopathic lupus, since renal and neurological lesions are rare and, when present, repress after the responsible drug is withdrawn. The presence of antinuclear antibodies is indispensable to the diagnosis. The detection of anti histones and denatured anti-DNA in the absence of anti-native DNA and/or anti-SM is the usual immunological pattern of drug-related lupus. PMID- 2237187 TI - [Sharp's syndrome]. AB - The author presents the current concept of Sharp's syndrome and mixed connective tissue diseases, as well as the detailed composition, determined by modern immunological methods, of the U1-RNP antigen against which patients with this syndrome develop antibodies. A physiopathological concept of the syndrome is outlined. PMID- 2237189 TI - [Treatment of lupus erythematosus disseminatus]. AB - Corticosteroids have transformed the prognosis of systemic lupus erythematosus (SLE), but no further advance has been achieved during the last few years. Treatment of SLE rests on the use, as rational as possible, of those therapeutic tools that are available. However, diagnosing SLE does not necessary, they must be given promptly in effective doses whilst preventing their side-effects, notably by the simultaneous management of atheroma factors. Non-steroidal anti inflammatory agents and synthetic antimalarial drugs may be used to replace corticosteroids or reduce their dosage. Severe forms of SLE which are function- or life-threatening require immunosuppressants, the best one being cyclophosphamide administered monthly as intravenous bolus injections, as this drug has been shown to be effective and to have low morbidity. Plasmapheresis is exceptionally needed. The risk of thrombogenesis due to the frequently associated "antiphospholipid syndrome" can be avoided by anticoagulants or antiplatelets the respective indications of which have not yet been clearly determined. SLE being a chronic disease, patient's compliance with treatment is very important and justifies the efforts made to train and inform these young male or female patients. PMID- 2237188 TI - [Contraception and pregnancy in systemic lupus erythematosus]. AB - In 1990 conflicting views are still being held concerning oral contraception and risks associated with pregnancy in women with systemic lupus erythematosus. As regards oral contraceptives, all authors agree that oestrogen-progestin combination pills are harmful, but the best alternative hormonal contraception remains to be determined. Protein-based "micropills" seem to be harmless; cyproterone acetate appears to be without side-effects, and its usefulness in preventing recurrences is being evaluated. As regards pregnancy, it would be wise not to contemplate having a child until 6 months have elapsed since the onset of remission. Blood pressure, platelet count and serum creatinine and uric acid levels must be closely monitored. Two types of antibodies may be present in the mother and are known to be responsible for foetal complications. These are antibodies to phospholipids (antiprothrombinase, anticardiolipin, antibodies responsible for dissociated treponema serology), which expose to spontaneous abortion or intrauterine death, and the antibody to SS-A (or anti-Ro), which exposes to foetal cardiomyopathy and congenital atrioventricular block. PMID- 2237190 TI - [Protein intake and kidney failure]. PMID- 2237191 TI - [Amyotrophic lateral sclerosis: Charcot's disease or a syndrome]. PMID- 2237193 TI - [The mysterious Doctor Davila]. PMID- 2237192 TI - [Therapeutical trials in arterial hypertension in 1990]. PMID- 2237194 TI - [Menopause. Diagnosis, consequences and principles of treatment]. PMID- 2237195 TI - [Mediterranean boutonneuse fever. Epidemiology, etiology, diagnosis, principles of treatment]. PMID- 2237197 TI - [Cancer of the esophagus. Epidemiology, etiology, diagnosis, development and prognosis, principles of treatment]. PMID- 2237196 TI - [Obstructive malformations of the upper urinary tract. Diagnosis, principles of treatment]. PMID- 2237198 TI - [Erysipelas, lymphangitis. Etiology, diagnosis, clinical course and prognosis, treatment]. PMID- 2237199 TI - [Renal regulation of the acid-base equilibrium]. AB - The kidney controls extracellular bicarbonate concentration and the pH of the body by modulating neat acid excretion (ammonium plus titratable acidity minus bicarbonate) according to the systemic acid-base balance. Proton, bicarbonate and phosphate transport and ammonium synthesis in the proximal tubules change in a homeostatic manner. The intercalycial A (proton secreting) and B cells (bicarbonate secreting) of the distal tubule and cortical collecting ducts have a high capacity of adaptation. The wide ascending branch of the loop of Henle also plays an important role in the bicarbonate and ammonium transport. Recent data suggest a pluri-hormonal regulation of urinary acidification. Therefore, the precision of the renal response to metabolic acidosis depends on the coordinated regulation of different segments of the nephron by the parathyroid hormone, aldosterone and the glucocorticosteroids. PMID- 2237200 TI - [Determination of pH in the body: methodologic review]. AB - The maintenance of a defined free H+ concentration within narrow limits is a prerequisite and feature of living organisms. In recent years the different disciplines of biological science have made considerable progress in the elucidation of the mechanisms involved in pH homeostasis. Recent advances have occurred also in the field of pH measurement. This review focuses mainly on the modern instruments for pH and blood gas analysis. The techniques of intracellular pH currently in general use are described together with some of the techniques for determination of pH in subcellular compartments. PMID- 2237201 TI - [Non-lactic metabolic acidosis]. AB - The definition of metabolic acidosis (MA) is a primary decrease in plasma bicarbonate concentration. The visceral consequences are largely dependent on the degree of acidosis and the rapidity of its onset; they have been studied mainly in animal studies and therefore, extrapolation to the clinical situation should be cautious. The MA can be classified in two groups according to whether the anionic serum gap is increased or normal (hyperchloremic acidosis). The etiologies of the first group are lactic acidosis, the cetoacidoses and renal failure. The hyperchloremic acidoses usually result from gastro-intestinal bicarbonate losses; the biochemical diagnosis of rarer causes of hyperchloremic acidosis is facilitated by measuring the serum potassium, urinary pH and the urinary anionic gap. Although all causes of MA must be treated, the use of bicarbonate should be discussed in each individual case. PMID- 2237202 TI - [Lactic acidosis and hyperlactatemia]. AB - Lactic acidosis is a relatively frequent acid-base disorder in a hospital setting. It is defined by the association of an arterial pH inferior to 7.35 and an arterial lactate level superior to 5 mmol/l. Classically, 2 types of acidosis are distinguished on the basis of their mechanisms of onset: the type A, with evident clinical signs of tissue hypoperfusion and the type B, more are, without apparent hypoxia. This last category is observed in various circumstances such as diabetes, acute liver failure, poisoning and, more rarely, inborn errors of carbohydrate metabolism. Treatment aims primarily at the correction of the cause. The efficacy of sodium bicarbonate is presently debated, considering the risk to worsen hyperlactatemia and to induce hyperosmolarity or rebound alkalosis. The administration of dichloroacetate, an activator of pyruvate dehydrogenase, permits to correct partially the lactic acidosis but is not harmless especially in case of prolonged administration. Other therapeutic modalities are evoked. Arterial lactate level is a reliable prognostic index of shock, because blood values do not depend only of the oxygen debt but also of the efficacy of hepatic and renal lactate uptake. Sequential measurements are recommended. PMID- 2237203 TI - [Renal acidosis]. AB - Normal adults with normal protein intakes have a urinary NH4 excretion of 40 to 50 mmol/24 hours and a variable urinary pH. In cases of metabolic acidosis a urinary pH less than 5.5 suggests an extra-renal origin whilst a urinary pH greater than 5.5 is in favour of renal acidosis, but there are many exceptions to this rule. On the other hand, urinary NH4 excretion is always greater than 70 mmol/24 hours in the first case and less than 40-50 mmol/24 hours in the second; and the use of the urinary anionic gap (Na + K - Cl), negative in the first case and positive in the second, enables the two situations to be distinguished. The acidosis of nephron reduction is easily recognised in cases of severe renal failure with an increase in unmeasured plasma anions whilst tubular acidoses are accompanied by a hyperchloremia. Measurement of fractional HCO3 excretion after an oral loading dose of NaHCO3, preferably by TmCHO3 with respect to GFR, distinguishes proximal tubular acidosis (low TmHCO3) from distal tubular acidosis (normal or high TmHCO3). In the latter case, the presence of hypokalemia suggests a distal tubular acidosis either due to deficiency of the H(+)-ATPase pumps (absence of increased urinary pCO2 after oral loading dose of NaHCO3) or to the inability of the kidney to maintain a normal H+ gradient (normal increase of urinary pCO2. The presence of hyperkalemia suggests diseases associated with hypoaldosteronism (low or inappropriate serum aldosterone concentrations), abnormal transepithelial voltages or with a pseudo-hypoaldosteronism syndrome (high plasma aldosterone concentration). The prevalence of distal tubular acidosis with hyperkalemia is on the increase whilst tubular acidosis with hypokalemia remains rare. PMID- 2237204 TI - [Metabolic alkalosis]. AB - Metabolic alkalosis (MA) only occurs after bicarbonate administration if given quickly and massively, or in the presence of renal failure. Most cases of MA are caused by a loss of hydrogen ions. This paper reviews the common causes (gastric aspiration, chronic diuretic therapy) and updates the list of drugs which may lead to this complication. Rare causes (such as hyper mineralo-corticoid secretion) should be suspected in patients with MA unresponsive to usual doses of potassium chloride. Hydrochloric acid infusions are reserved for very special cases. PMID- 2237205 TI - [Computer and acid-base disorders]. AB - The diagnosis of acid-base disorders has been subject to computerised analysis for many years. Expert systems, an application of artificial intelligence, have been validated. They are of help to clinical decision making, enabling the different diagnostic possibilities of given acid-base and hydro-electrolytic situations to be evaluated and appropriate therapy to be instituted. Computer networks improve the transmission of laboratory results to the intensive care units and the integration of data facilitates the monitoring of biochemical tendencies. Computers can also be used for teaching acid-base physiology and pathology. PMID- 2237206 TI - [Clonidine in anesthesia and in intensive care: rejuvenation of a compound?]. PMID- 2237207 TI - [Tropical spastic paraplegia (TSP) and HTLV1 associated to paraplegia (HAP)]. PMID- 2237208 TI - [Motor disorders of the esophagus]. PMID- 2237209 TI - [History of medical responsibility]. PMID- 2237210 TI - [Hernias. Diagnosis, principles of surgical treatment]. PMID- 2237211 TI - [Acute fever. Diagnostic orientation and management]. PMID- 2237212 TI - [Venous thrombosis of the lower limbs. Etiology, physiopathology, diagnosis, clinical course and prognosis, treatment]. PMID- 2237213 TI - [Spontaneous abortion. Diagnosis, course and prognosis, treatment]. PMID- 2237215 TI - [Epidemiology of HTLV-I infection in its hyperendemic foci (Japan, tropical Africa, Caribbean)]. AB - HTLV-1 infection is endemic in Japan, black Africa, the Caribbean and several regions of South America. In these foci, the infections is very heterogeneously distributed (variations from village to village, intrafamilial clustering). The virus is transmitted from mother to child, and breast feedings seems to play a major role. Sexual transmission is usually from man to woman. The frequency of transmission by blood transfusion must not be underestimated. It justifies the systematic detection of HTLV-1 infection in areas where it is economically feasible. PMID- 2237214 TI - [Polyuriapolydipsia syndrome. Diagnostic orientation and management]. PMID- 2237216 TI - [Neurologic pathology and HTLV-I virus]. AB - In most cases the only manifestation of nervous system pathology associated with HTLV-1 infection is spastic paraplegia. The virus is transmitted by breast feeding from mother to child, by transfusion of contaminated blood (or by syringes of intravenous drug addicts) or sexually from husband to wife. Paraplegia usually begins progressively after the age of 30 years by motor and sphincteral disorders, followed by a phase of stabilization. Other clinical entities, such as pseudo-LAS syndromes, polymyositis, lymphocytic alveolitis, vasculitis or meningitis, may coexist or show varying degrees of expression. There is no treatment capable of modifying the course of the disease, but corticosteroids are worth trying, notably in the initial stages of paraplegia and in polymyositis. PMID- 2237217 TI - [Malignant strongyloidiasis and the HTLV-I virus]. AB - A significant association between Strongyloides stercoralis and HTLV-1 infections has been demonstrated in areas (such as southern Japan and the Caribbean) where HTLV-1 is endemic. Due to the immunomodulating effects of the virus and the parasite, patients with both infections would be at risk for overwhelming strongyloidiasis as well as for T-lymphocyte haemopathy. S. stercoralis is thought to be a cofactor for viral replication and leukaemogenic power. PMID- 2237218 TI - [HIV infection and "malignant" strongyloidiasis]. AB - Disseminated Strongyloides stercoralis infection occurs in immunocompromised patients. Despite the epidemiological overlap of HIV infection and strongyloidiasis observed in certain parts of the world, only six cases of dissemination have been reported in AIDS patients. The clinical presentation has no special features, except for the frequency of other opportunistic infections. The prognosis is poor. This lack of association between disseminated strongyloidiasis and HIV infection had led to the exclusion of extra-intestinal forms of this paraistosis from the revised classification of AIDS. PMID- 2237219 TI - [Epidemiology of HIV infections in Africa]. AB - Africa is the continent most severely affected by the pandemic of immunodeficiency viruses (HIV-1 and HIV-2). Nowadays (1990), at least 3 million individuals are infected and about 300,000 cases of acquired immunodeficiency syndrome (AIDS) have been recorded. HIV infections started in the seventies as sporadic cases in remote areas and spread throughout black Africa where they are now epidemic, with high seroprevalence (1p. 100-20 p. 100), even in the general population. Due to heterosexual transmission, the groups at highest risk are female prostitutes and their customers and people with genital ulcers and/or sexually transmitted diseases (STDs). The vertical infection rates remain uncertain but may be estimated at 40 to 65 p. 100 of pregnancies in HIV-infected mothers. Blood transfusions are the third mode of infection because of high demands for blood (sometimes not tested) arising from severe anaemias in children (malaria and sickle cell anaemia), in pregnant women and in patients needing surgery. STDs causing ulcers undoubtedly are cofactors in the invasion by HIV, while the most important cofactors in AIDS progression are recurrent STDs, chronic activation of the immune system and repeated pregnancies that activate HIV-infected lymphocytes. The minimum mortality rate of AIDS is about 1 in 5000. Spatial, cultural and demographic factors should also be taken into consideration for all AIDS control programmes which must be integrated into the primary health care systems of African states. PMID- 2237220 TI - [Clinical aspects of AIDS in Africa]. AB - The clinical manifestations of HIV infection in Africa are similar to those observed in Europe and North America. However, some features related to ecological and diagnostic factors give the disease a certain African peculiarity. In more than 80 p. 100 of the cases AIDS is characterized by deep alteration of the subject's general condition, with chronic diarrhoea, severe asthenia, prolonged fever and massive loss of weight. This "slim disease" is only found at the terminal stage of AIDS in North America. Opportunistic infections are multiple, often associated, and their frequency differs from that found in Europe and the USA. Thus, pulmonary pneumocystosis is rare (12.5 to 21 p. 100 of the cases, as against 50 to 80 p. 100 in Europe). Isosporosis is frequent (4 to 48 p. 100 of the cases instead of 0.2 p. 100 in the USA), and this also applies to cryptosporidiosis (7 to 21 p. 100 of the cases, compared with 3.3 p. 100 in the USA). Gastrointestinal candidiasis occurs in 21 to 49 p. 100 and cryptococcosis in 10 to 30 p. 100 of the patients. Material problems make it impossible to evaluate the prevalence of certain infections, notably toxoplasma and CMV infections. The prevalence of Kaposi's sarcoma is low (15 to 20 p. 100). Dermatological manifestations occur at an early stage and are both common and varied (papular eruption, prurigo, herpes zoster, changes in the hair and skin appearance); they characterize the "African aspect" of AIDS. Tuberculosis is particularly frequent: in Africa, 30 to 40 p. 100 of tuberculous patients are HIV seropositive, as opposed to 10-25 p. 10 in Western countries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237221 TI - [HIV infection and malaria]. AB - In sub-Saharian Africa, most HIV seropositive subjects carry either haematozoa (especially children) or antimalarial antibodies. Despite a transient decrease in cell-mediated immunity during malarial paroxysms, Plasmodium falciparum malaria does not seem to influence the course of the HIV infection. Paroxysms may be slightly more frequent or slightly more severe in HIV seropositive subjects, but they raise no diagnostic or therapeutic problem. Some cases of HIV contamination have been attributed to the blood transfusions required by malaria-induced anaemia. Prophylactic measures include early chemotherapy of malaria and detection of dangerous blood donors, if necessary by quick tests. Modern HIV tests avoid most of the false-positive reactions sometimes observed during malaria. PMID- 2237222 TI - [Tegretol in psychiatry]. PMID- 2237223 TI - [Chromosomal abnormalities in colorectal cancers]. PMID- 2237224 TI - [Bone marrow aplasia and artificial respiration]. PMID- 2237225 TI - [Epidemic asthma]. PMID- 2237226 TI - [Haemophilus influenzae type B infections: epidemiology, prospects for vaccination]. PMID- 2237228 TI - [Paget's disease. Diagnosis, principles of treatment]. PMID- 2237227 TI - [Historical research on the discovery of nystagmus and its physiopathologic significance]. PMID- 2237229 TI - [Acute pancreatitis. Etiology, diagnosis, course and prognosis, principles of medical and surgical treatment]. PMID- 2237230 TI - [Diplopia. Exploration of the extrinsic and intrinsic motricity]. PMID- 2237231 TI - [Cancer of the floor of Mouth, cheeks, lips, palate and gingiva. diagnosis, principles of treatment]. PMID- 2237232 TI - [Chronic lymphoid leukemia. Diagnosis, development and prognosis]. PMID- 2237233 TI - [The effect of repeated fasting on the ratio of individual fatty acids in the brain and blood of rats of various ages]. AB - In locally bred, 5-day old and full grown rats, the authors conducted experiments where they investigated the influence of repeated fasting (3 X 18 hours food deprivation on three consecutive days) on a wide spectrum of fatty acids in the cerebral cortex, medulla oblongata and serum. The fatty acids were assessed as methyl esters by gas chromatography, as described in previous work (1, 13, 14, 17). In 5-day old rats after repeated fasting an evident decline in the ratio of saturated fatty acids in serum was recorded; at the same time the ratio of arachidonic acid increased markedly and in the cerebral cortex there was a significant drop of the palmitic acid participation. In adult rats 16 statistically significant changes took place (treble as compared with the 5-day old rats). The large number of significant changes pertained to 18 carbon fatty acid (a rise in all instances in the brain; the ratio of 18:3n-6 in plasma declined significantly). In the serum of adult rats the ratio of arachidonic acid increased also. The authors discuss possible reasons of the described changes. PMID- 2237234 TI - [Is the argon laser suitable for angioplasty procedures?]. AB - Laser angioplasty is a perspective method for the treatment of complications of atherosclerosis of peripheral and coronary arteries. The present study deals with the effects of an argon laser on cadaverous coronary arteries with atherosclerotic plaques. Radiation of the argon laser created in the plaque a circular defect with a singed margin. The energy of radiation being equal, the size of the defect depended on the position of the optic fibre -- it was greatest when the optic fibre was in contact with the plaque. The defect thus formed had uneven margins with adjacent layers of thermal damage which were larger in calcified plaques than in fibrous and fibrolipomatous plaques. Penetration of radiation into the plaque depended on its composition -- being least in calcified plaques. When the arteries were rinsed with saline during irradiation, the effect of radiation on the tissue was reduced as the tissue was cooled. The argon laser causes greater thermal damage of the arteries than pulsed lasers and therefore its clinical application will be restricted. PMID- 2237235 TI - [The effect of corticoids on bone tissue in myasthenia gravis]. AB - Myasthenia gravis is an autoimmune disease where corticoids are the basis of therapy. They are taken for short periods in large amounts, as well as for prolonged periods in medium or small doses. The authors investigated in the described groups the effect of corticoids on bone tissue. They provided evidence of a significant effect on the diffraction pattern, geometrical arrangement of the apatite grid and ion changes in relation to the period of corticoid administration without significant clinical manifestations of osteoporosis, when respecting therapeutic principles. PMID- 2237236 TI - [The relation of nucleoli to precancerous conditions of the cervix]. AB - Oestrogens act at the nuclear level. To these steroids also a cancerogenic effect is ascribed. By staining for nuclear structures according to Smetana and Busch the authors proved morphological structures of the nucleolus in vaginal epithelia and in cells from cervical lesions. This applies to solid nucleoli -- which are active, annular nucleoli which are resting and nucleoli which have completed their activity -- micronucleoli. Hyperoestrogenic women have in their vaginal epithelia of the upper third of the vagina more active nucleoli (11.4%) than hypooestrogenic women (2.1%). Women suffering from cervical carcinoma during the menopause have more active nucleoli in the vaginal epithelia (30.8%), as compared with healthy hyperoestrogenic women of productive age. Patients during the menopause with grade III dysplasias have fewer active nucleoli in cervical epithelia than women with cervical cancer (25.0%), however, as compared with hyperoestrogenic women of productive age, much more. A large number of active nucleoli was proved by staining by Smetana's method also in cells taken from cervical lesions carcinoma type and grade III dysplasia in postmenopausal patients. Evaluation of morphological changes of the nucleoli suggests their activity, the activity of the whole nucleolus and is a sensitive indicator of the activity of the whole cell. PMID- 2237237 TI - [Possibilities of comprehensive care of oncologic patients in the framework of a polyclinic facility]. AB - The authors evaluated five years of experience with ambulatory cytostatic chemotherapy at the policlinical department of clinical oncology in the District Institute of National Health in Prague 4. At the same time they draw attention to the necessity to create an in-patient department for oncological patients in this area. PMID- 2237238 TI - [New aspects of intolerance of the aqueous iodinated x-ray contrast medium, adipiodone--fatal interaction of adipiodone-Ultrabil with the immunomodulators Corynebacterium parvum (CP) and Shigella dysenteriae endotoxin (LPS)]. AB - The authors assume a new type of interaction of the aqueous X-ray contrast substance type adipiodone (Ultrabil 50% Spofa) with immunomodulators of Corynebacterium parvum (CP) and the endotoxin of Shigella dysenteriae (LPS). The fatal type of interaction developed regularly as a result of the concurrent i.v. administration of the X-ray contrast substance adipiodone with the endotoxin of Shigella dys. (LPS) to laboratory animals (mice) which had five days previously a single dose of Corynebacterium parvum (CP). The effect of the interaction was evaluated using LD50 of adipiodone (Ultrabil Spofa) which in interaction with the immunomodulators of CP and LPS was identical as the dose used in diagnostic practice. The authors considered the possible development of "oxygen stress" as a consequence interacting processes and complement activation. PMID- 2237239 TI - [Auditory function in children and adolescents with diabetes mellitus]. AB - The authors examined by audiometry 49 diabetics aged 3-18 years. Of these 47 patients aged 6-18 years (23 girls and 24 boys) were evaluated. A hearing disorder was found in four children. In one instance a conduction disorder after repeated otitis media was involved. In three children, i.e. 6.4%, perception hypacusia was found (once bilateral, twice unilateral). Based on the mentioned findings, the authors recommended systematic monitoring of the auditory function of all diabetic children. PMID- 2237240 TI - [History of the beginnings of Czech stomatology]. AB - The authors present a brief account of the history of dental surgery--stomatology -in Bohemia and Moravia from the very beginnings to the period after the Second World War with indicators of the brisk development of the discipline in the new democratic state which occurred in particular after the foundation of the stomatological branch of medical faculties in 1950/51. The authors mention in more detail only the main personalities and representatives of the discipline who contributed most to the development, being aware that they collaborated with several tens of teachers and research workers of more than four generations who also deserve admiration and gratitude. PMID- 2237241 TI - [Use of a new type of hydrogel in bone surgery]. AB - The authors submit information on the properties of a new macroporous hydrogel, which was synthetized specially for use in bone surgery. In animal experiments the authors evaluate microscopically the biocompatibility and process of biodegradation of the implant in osseous tissue. PMID- 2237242 TI - [Prevalence of mineralization disorders in dental tissues in children in fluoridated regions of Kladno]. AB - The authors subjected to dental examinations a group of children aged 12-13 years from the Kladno area and surrounding rural communities. The children from Kladno drank from birth fluoridated water from the water mains, while the rural children, where well water had a minimum fluoride content, had to rely on sodium fluoride tablets. In all children the prevalence of non-carious changes of dental tissues was assessed, the cariosity (DMF), oral hygiene (OHI) and the state of the gingiva (PI). The objective was to assess to what extent and in which indicators the urban and rural children differ. The results were compared with the status in Prague children who were not exposed to fluoride during the first years of life. The results revealed that the Kladno children differ only as regards cariosity which is significantly higher in the rural children. This finding can be explained by irregular intake of sodium fluoride tablets. As compared with Prague children, there was a marked difference in the prevalence of non-carious changes of dental tissues in favour of the children from the Kladno area. Their cariosity was also significantly lower. The results provide evidence that fluoridation of drinking water is not only the most effective way how to prevent caries but that it prevents also inadequate mineralization of dental tissues. PMID- 2237243 TI - [Oral health in cariology and endodontics to the year 2000]. AB - In 1978 the World Health Organization proclaimed the programme "Health for All by the Year 2000". In 1982 the International Stomatological Federation joined this programme with "Oral Health by the Year 2000". It comprises actual anti-caries targets for various age groups, e.g. 50% of 65-year-old subjects should have 20 natural functional teeth. Comparative investigations indicate that the above programme is successfully implemented in those developed industrial countries where it has become a matter of course for the wide public and where in its implementation also non-stomatological medical disciplines participate. The purpose of the present paper is to remind of some comprehensive coordinated aspects of caries prevention and some most frequent complications of caries, i.e. pathological conditions of the dental pulp and apical periodontium. PMID- 2237244 TI - [Current views on periodontosis]. AB - Diseases of the suspensory dental apparatus are very widespread. Its consequences and course frequently lead to restriction of dental function and frequently also to loss of teeth with adverse health, social and economic sequelae. The objective of the present paper is to makes doctors of non-stomatological disciplines familiar with contemporary views on the genesis and therapy of these diseases. PMID- 2237245 TI - [Differential diagnosis in painful dysfunctions of the mandibular joint]. AB - The painful dysfunctional syndrome of the mandibular joint is characterized by an impaired functional equilibrium of the masticating apparatus, the main constituents of which are the mandibular joint, the masseters and dentition. The symptoms associated with the syndrome are usually non-specific and are found also in other diseases of the orofacial region. The author describes some pathological conditions which may be mistaken for painful dysfunctional syndrome, in particular if they take an atypical course with a less marked symptomatology. PMID- 2237246 TI - [Aspects of corticoid therapy in patients with pemphigus and pemphigoid in the oral cavity]. PMID- 2237247 TI - [Rehabilitation of the dentition using intraosseous blade implants]. AB - Intraosseous blade vent implants extend hitherto existing clinical methods of prosthetic treatment of some conditions of defective teeth by new possibilities. It is a method which can produce satisfactory and long-term results. One of the prerequisites is, however, that generally valid and local limitations for indication of the implantation will be respected, that the implantation will be implemented by reliable surgical technique along with high standard prosthetic treatment which in the course of recovery will carry the implant to its functional period. Results of our investigations revealed unequivocally that the use of implants with a low or predominantly low intraosseous part leads in the majority to unsatisfactory results of implantations. PMID- 2237248 TI - [Phagocyte function deficiency determined by methods using chemotaxis and chemiluminescence]. AB - The chemotactically oriented and not oriented migration of polymorphonuclear leucocytes was examined in 21 patients with acute ulcerative gingivitis, using the method of assessment of chemotaxis under an agarose layer. In the same group of patients also the chemiluminescence of leucocytes was assessed. In 16 patients the chemotactically oriented and non-oriented cell migration was reduced. In four patients both types of activity were enhanced. The chemiluminescent leucocyte activity was reduced in all patients of this group. PMID- 2237249 TI - [Complex stomatologic care in patients with anorexia nervosa]. AB - The authors describe a group of 25 patients with anorexia nervosa treated at the Psychiatric Clinic, First Medical Faculty, Charles University. They compare their experience with dental treatment of these patients with data in the literature. Extensive dental damage in these patients calls for comprehensive dental care which is not only time consuming but frequently also pretentious from the economic aspect. The authors recommend therefore dispensary care and emphasize the necessity of collaboration between the psychiatrist and stomatologist. PMID- 2237250 TI - [Training in social competence in undergraduate education in pediatric stomatology]. AB - Hitherto practised training revealed that in the undergraduate training in paedostomatology there are disproportions between the shaping of the professional skill and the formation of professional social and psychological qualities of the student. The consequences of the one-side attention of teaching to professional training are manifested already during clinical practicals and during the implementation of systematic dental care in practice. The authors innovated the programme of undergraduate training in paedostomatology. This resulted in rationalization, not extension of the training at the expense of other subjects. As far as stomatological training is concerned, they adhered as regards scope and contents to the hitherto existing seven thematic entities of the uniform curriculum. A new subjects, psycho-social training was included where students are not taught only basic theoretical knowledge; methods of social training were applied and students are taught the necessary practical skills. The method was applied so far for five years in the training of paedostomatology at the First Chair of Stomatology. The acquired experience justifies the statement that the method was accepted by members of the department (of all categories), child patients and parents. The children become rapidly familiar with the technique of substitutional signals of communication. During subsequent visits they do not require treatment by the same doctor but adherence to the ritual. The change of the general style of training enables the teacher to make the students familiar in a more instructive manner with the basic principles of three-step preventive care, to teach the students not to treat but to "be a doctors". By simulation of field practice in the final part of the clinical course training was approximated to the actual procedure in practical work. PMID- 2237251 TI - Autoradiographic localization of receptor sites of 3H-spiroperidol in the CNS of rat. AB - Our study presents macroautoradiographic maps of the distribution of 3H spiroperidol in the CNS of rat. The radioactively labeled butyrophenone neurolepticum enables in vivo after brain intraventriculo-cisternal perfusion an exacter autoradiographic localization of dopamine receptors in various regions of the brain. For the first time 3H-spiroperidol has been administered by intraventriculo-cisternal perfusion. Also original are the finding of receptor labelling by means of 3H-spiroperidol on astroglia and in the spinal grey matter. PMID- 2237252 TI - Statistical properties of ABR amplitudes and latencies. Implications for computation of reference limits and relation to click phase. AB - A method for statistical analysis and computation of reference limits for ABR latency and amplitude variables is presented. Condensation and rarefaction ABRs from 47 healthy controls aged 4-58 years were investigated. With respect to gaussianity of distributions, the square root transformation was superior to the logarithmic transformation for amplitudes, while the logarithmic transformation performed better for amplitude ratios. Wave V latency and the I-V interpeak latency were nearly normally distributed, while other latencies and inter-peak latencies displayed varying displacement from a normal distribution. Rarefaction ABR distributions were slightly closer to normality than were condensation ABRs. Amplitude vs. following amplitude and latency vs. amplitude correlation coefficients were larger for R than for C click ABRs; thus R clicks seem to evoke a better synchronized neural volley. Most of the correlation between amplitude and latency could be explained by the influence of age and sex. Hence, age and sex matched reference limits for ABR amplitudes, without correction for latency, seem to be adequate in practical clinical work. PMID- 2237253 TI - Intensity operating range measures as predictors of word-recognition ability in cochlear implant subjects. AB - The purposes of the experiment were to examine the appropriateness of pre- and post-implant intensity measures (thresholds, most comfortable listening level, and loudness discomfort level) as predictors of post-implant phoneme-recognition ability and to study the relationship between pre- and post-implant intensity measures. Pre-implant intensity measures were obtained on 16 subjects who were eventually implanted with either a Nucleus device (n = 8) or a Symbion device (n = 8). Phoneme scores on a NU-6 word list were obtained on these 16 subjects at 1 month post-implant. Post-implant intensity measures were also made on the 8 Symbion subjects at 1 month post-implant. The results showed that none of the pre implant intensity measures correlated significantly with post-implant phoneme scores. In addition, pre-implant intensity measures did not correlate with the same post-implant intensity measures. However, post-implant MCLs and LDLs correlated significantly with phoneme scores as reflected by correlation coefficients that were larger than 0.8. These preliminary results suggest that although intensity measures may relate to phoneme-recognition ability, their use as predictive measures (as in pre-implant measures) for post-implant ability is questionable. PMID- 2237254 TI - Hypoacusis among the Polar Eskimos of northwest Greenland. AB - Audiological tests were conducted on 188 Polar Eskimos (75 males and 43 females) in small, remote, nonindustrialized settlements of Northwest Greenland. Most males of this small Eskimo tribe hunt regularly for food using rifles and shotguns. The means of the pure tone hearing thresholds indicated that 77% of the males in the population sample had a hearing loss (greater than 25 dB HL) in the high frequency range (above 2,000 Hz), in one or both ears. Also, 73% of the males had bilateral hearing losses (greater than 25 dB HL), and 73% had hearing thresholds greater than or equal to dB in one or both ears. A high frequency hearing loss was found in 46% of the males of the younger age groups (less than or equal to 40 years), mainly in the 3,000 to 8,000 Hz range, with the mean loss gradually extending to 2,000 and 1,000 Hz, and increasing in severity with age. The mean pure tone thresholds of 6- to 60-year-old female Polar Eskimos (who do not hunt with firearms) were generally within normal limits over the entire audiometric frequency range for the younger groups, and increased with age to the mild hearing loss range. Among the females, 35% had a hearing loss (less than 25dB HL) in the high frequency range (above 2,000 Hz) in one or both ears, and 21% had thresholds of greater than or equal to 50 dB in one or both ears. Conductive hearing losses in the low frequency range were not widespread among the males or females of this survey. The findings of this study suggest: (1) The high incidence of age-related hearing loss among the Polar Eskimo males is the result of frequent exposure to high intensity, impulse firearm noise, which is the major source of noise for this population, in an otherwise "noise-free" environment. (2) The primary noise-induced permanent threshold shift among Polar Eskimo hunters occurs in the age range of 10-40 years, and increases slowly thereafter, mainly as a result of continual noise exposure and presbyacusis. It is recommended that ear protectors and a comprehensive hearing conservation/rehabilitation program be provided for the Polar Eskimo population at once in order to prevent further hearing impairment and to rehabilitate those persons presently suffering from hearing loss. PMID- 2237255 TI - An electrical network model of inertially induced bone-conducted sound. AB - A model for the description of inertially induced bone-conducted sound has been developed and a discussion of the appropriate techniques for its representation as an electrical network is described. Predictions are made for the sound pressure produced in the meatus in the cases of normal ears and pathological ears resulting from vibration applied to the skull. Evidence from this modelling suggests that the technique may provide improved discriminability over conventional immitance measurements for some types of pathology. PMID- 2237256 TI - Brain stem (ABR) and middle latency (MLR) auditory evoked responses in infants. AB - We examined ABRs and MLRs for click and/or 500-Hz tone pip stimuli in infants (36 44 weeks conceptional age) admitted to the NICU and measured the threshold and detectability of those responses. We took the threshold indicators of those responses as Jewett V for ABR measurement and wave PO Nal Na2 for MLR measurement. Thresholds of MLRs for click stimuli were almost equal to those of ABRs for click stimuli. On the other hand, thresholds of MLRs for 500-Hz tone pip stimuli were slightly worse than ABRs for click stimuli, the average differences being less than 10 dB. Wave Po Nal Na2 are the best threshold indicators of MLRs in infants, but the diagnostic significance of wave Pa was questionable in our measurements. PMID- 2237257 TI - Individual differences in auditory electric responses: comparisons of between subject and within-subject variability. IV. Latency-variability comparisons in early, middle, and late responses. AB - In this series of reports to date (Lauter & Loomis, 1986, 1988; Lauter & Karzon, 1990 a & b) we have described patterns of relative variability observed in latency and amplitude of auditory brainstem responses (ABRs) collected in a repeated-measures within-subjects design testing two groups of neurologically normal adults. Each of the two groups of subjects was additionally tested for one other type of auditory evoked potential, according to the same schedule of eight weekly sessions: middle-latency responses (MLRs: 10 to 50 ms post-stimulus) were collected from Group II (four females and four males), and late responses (50 to 300 ms post-stimulus) from Group I (four females and three males). This paper presents data comparing and contrasting the patterns of relative variability of waveform-peak latency observed in middle-latency, late responses, and the ABR data previously reported. Results document a trimodal distribution of response latency variability, with ABR peak V in one category, characterized by high within-subject stability and low between-subject stability, ABR peaks II, III, and IV, together with MLR peak No in a second category, of intermediate within subject stability, and a third category consisting of ABR peak I together with all auditory-evoked-potential (AEP) peaks subsequent to MLR peak No, in which consistency of peak latency calculated within subjects approaches the low level of consistency calculated across subjects. PMID- 2237258 TI - Different tympanometric procedures compared with direct pressure measurements in healthy ears. AB - Different tympanometric procedures were compared regarding their reliability and systematic differences in middle ear pressure estimation in healthy adults. In a second part of the study the accuracy of measurement was judged by correlating tympanometric readings, obtained by using the different procedures, with known pressure levels applied after cannulating the mastoid air cell system. There were no significant differences in reliability between the different tympanometric procedures tested (p greater than 0.05). However, forward-backward tracing tympanometry and 'zero sweep rate' tympanometry gave smaller errors in the middle ear pressure estimates than the conventional decreasing pressure sweeps. Forward backward tracing tympanometry at high sweep rate is recommended both for pressure measurements during physiological studies and in clinical practice. PMID- 2237259 TI - Reproducibility of hearing threshold measurements. Supplementary data on bone conduction and speech audiometry. AB - The reproducibility of bone-conduction pure-tone audiometry and speech recognition thresholds has been tested in groups of normal-hearing subjects. Each person was tested twice during the same day, and the test-retest difference was calculated. The reproducibility is presented as the standard deviation of this difference. Bone-conduction threshold measurements have a high degree of test retest precision, whereas air-bone gaps show a large range of distribution in these normal-hearing subjects. This makes the interpretation of such gaps spurious when values are below 20-30 dB. Speech recognition threshold has the highest degree of test-retest precision of all audiometric tests, and this is probably due to the steep slope of the psychometric function at 50% intelligibility. A more detailed graphic presentation of the 50% point of intersection will bring the reproducibility down to less than 2.5 dB. PMID- 2237260 TI - Clinical evaluation of cathodic trypsin-like immunoreactivity in pancreatic diseases in adults. PMID- 2237261 TI - HPLC separation and quantification of bilirubin and its glucuronide conjugates in faeces and intestinal contents of germ-free rats. AB - We describe an accurate reverse-phase high-performance liquid chromatography (HPLC) method for the separation and quantification of unconjugated bilirubin (UCB) and its monoglucuronide (BMG) and diglucuronide (BDG) conjugates in faeces and intestinal contents from germ-free (GF) rats. We demonstrated that female GF rats excreted predominantly BMG and that the percentage of this conjugate was at most 71.7% of the total bilirubin excreted with the faeces. The highest percentages for BDG and the UCB were 27.9% and 6.0%, respectively. The bile pigment composition in duodenal contents was 59.8% BDG and 40.2% BMG (median percentage) and was 47.7% BDG, 50.1% BMG and 2.2% UCB in ileal contents. Deconjugation of BDG to BMG was profound in caecal contents with 26.0% BDG, 67.4% BMG and 6.6% UCB. Endogenous (mammalian) beta-glucuronidase activity was present in intestinal contents throughout the entire length of the intestine and in faeces of the GF rats. The results indicated that it is very likely that endogenous beta-glucuronidase plays a role in the deconjugation of bilirubin glucuronides as well as of other glucuronides in the intestine of the GF rat. PMID- 2237262 TI - A review of 23Na nuclear magnetic resonance spectroscopy for the in vitro study of cellular sodium metabolism. AB - Changes in intracellular sodium have been associated with a number of different diseases. Consequently, various methods have been used to quantify the level of intracellular sodium concentrations. Traditional methods like flame photometry and ion-selective electrodes are destructive or invasive, thereby potentially altering the intracellular sodium levels. There has been an increasing interest in evaluating the method of 23Na nuclear magnetic resonance in recent years, since this method allows for non-invasive continuous monitoring of intracellular sodium in cell suspensions and tissues. A phenomenological approach to basic theory, review of methodology, applications to the in vitro study of cellular sodium metabolism, and difficulties of interpretation of this analytical modality is presented. PMID- 2237263 TI - Levels of neutrophil elastase and cathepsin B activities, and cystatins in human sputum: relationship to inflammation. AB - Sputum samples from 25 patients with bronchiectasis were assayed enzymatically for myeloperoxidase, neutrophil elastase and cathepsin B, and immunologically for cystatin A, cystatin B, cystatin C, cystatin S and kininogen. High myeloperoxidase and neutrophil elastase levels were found in those sputum samples that were assessed visually to be purulent. These samples were also found to contain high levels of cathepsin B activity and cystatin A, but low levels of cystatin S and of the most effective cathepsin B inhibitor, cystatin C. In contrast, sputum samples that were low in myeloperoxidase and neutrophil elastase activities had low levels of cathepsin B and cystatin A, but high cystatin C and S levels. It is concluded that cathepsin B activity in sputum is positively correlated with the degree of inflammation and neutrophil recruitment. Although this may be due in part to reduced amounts of cathepsin B inhibitors, particularly cystatin C, theoretical considerations suggest that factors other than the gross level of inhibitors must be involved in the control of cathepsin B activity. PMID- 2237264 TI - Bone mass measured by photon absorptiometry: comparison of forearm, heel, and spine. AB - We assessed bone mass quantification at different skeletal sites by single and dual photon absorptiometric (SPA and DPA) methods. Improved DPA measurement of spinal bone mineral density in young healthy subjects showed a short- and long term precision of 1.2% and 1.6%. Compared to the conventional DPA method the imprecision was reduced by more than 50%. The appendicular measurements were more precise (0.5-1.2%). We present the intercorrelations and predictive errors between peripheral measurements and improved spinal and total body bone measurements in early postmenopausal women (n = 144) recruited in 1988. To compare the improved system with the conventional methods, we retrieved data on age-matched early postmenopausal women (n = 151) recruited in 1983. In the 1988 population all peripheral methods had similar predictive errors in estimation of spinal bone mineral density (SEE = 11-13%) and total body bone mineral density (SEE = 4-5%). Measurement of trabecular bone in the heel and distal forearm did not improve the validity of predicting spinal bone mass. In a cadaver study (n = 11) the predictive error in estimation of the spinal ash weight from forearm measurements was of the same magnitude (15%) as that in estimation of the spinal BMC from the forearm (16%). We conclude that the predictive error in estimation of spinal bone mass from peripheral bone measurements is more likely to be caused by intra-skeletal variation in bone mass than by precision errors. However, this does not reflect the inability of peripheral bone mass measurements to predict fracture risk. PMID- 2237265 TI - Accuracy of pulse oximetry during moderate exercise: a comparative study. AB - This study was designed to discriminate, according to their accuracy, between eight pulse oximeters (PO) using a realistic evaluation performed by means of a moderate exercise to provide artefacts and thus represent a typical clinical situation. Accuracy was assessed by calculating error on saturation (EOS) as the difference between simultaneous measurement of non-invasive (SpO2) and invasive functional (SfO2) arterial blood oxygen saturation. An index of homogeneity of EOS (InH), calculated using a Lehmann analysis, was chosen as a representative of error dispersion, leading to a statistical classification; the influence on error introduced by the drift of EOS with SfO2 was thus eliminated. We obtained a clear cut separation of the eight PO (Datex Satlite (DA), Kontron 7840 (KO), Nellcor 200 (NE), Novametrix 505 (NO), Ohmeda 3700 (OH), PPG-Hellige (PP), Physiocontrol 1600 (PH), and Radiometer Oxi (RA] into two statistically different subgroups by comparing their InH standard deviation (SD). There is a highly statistically significant difference between the accuracy measured for the high precision subgroup with an InH SD ranging from +/- 1.6 to +/- 1.9% SaO2 (DA, PH, and RA), and that measured for the low precision subgroup whose InH SD ranges from +/- 2.8 to +/- 5.0% SaO2 (NE, OH, NO, KO, PP). These results suggest that, in our clinical conditions, there is a wide range of inhomogeneity of error from one PO to another. The error introduced by the drift of EOS with SfO2 should be considered separately. PMID- 2237266 TI - Analysis of purine nucleotides in muscle tissue by HPLC. AB - Optimal conditions for simultaneous analysis of the purine nucleotides adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine, adenosine, hypoxanthine, xanthine and uric acid in muscle samples by high-performance liquid chromatography (HPLC) were evaluated. A neutralized perchloric acid extract of freeze-dried human or rat skeletal muscle tissue was injected on to a reversed-phase silica column and eluted by a gradient composed of ammonium dihydrogen phosphate buffer and methanol. Good resolution for all the nucleotides was achieved within a retention time of about 20 min. Linearity for each of the nucleotides within the concentration intervals obtained in the samples was demonstrated. Purity of each peak was verified by use of the photodiode array technique. Reproducibility for biological samples with variation coefficients below 3.6% for ATP, ADP, AMP, inosine and hypoxanthine and 6.7% for IMP was obtained. The stability of the compounds after extraction was specifically addressed. Storing of frozen extracts at -20 degrees C for 24 h gave acceptable values, while storage for 7 days cannot be recommended. Storage of unfrozen extracts at 4 degrees C was acceptable for (up to) 7 h. This technique provides a sensitive, convenient and reliable method for simultaneous analysis of a large number of purine nucleotides in small skeletal muscle biopsies, provided that certain precautions are taken with respect to the instability of these metabolites. PMID- 2237267 TI - Prevalence of anti-insulin antibodies and its relation to severe hypoglycaemia in insulin-treated diabetic patients. AB - The prevalence of anti-insulin antibodies (AIABs) and their association with clinical parameters, metabolic control and severe hypoglycaemia were investigated in a geographically defined population of insulin-treated diabetic patients. Eighty per cent of the patients (479) delivered venous blood samples and answered a questionnaire on severe hypoglycaemic problems during a 12-month period. Circulating AIABs were demonstrable in 78% of the patients, being more common among those with type 1 diabetes and in long-duration patients. High levels of AIABs were also more frequent in patients in whom insulin treatment had been initiated prior to the era of highly purified insulins. The AIABs did not correlate to metabolic control, insulin dose or severe hypoglycaemia. It is concluded that AIABs is not a risk factor for severe hypoglycaemia in insulin treated diabetic patients. PMID- 2237268 TI - Serum ferritin, iron status and plasma ascorbic acid in 40- to 49-year-old males in the Faroe Islands. AB - Iron status (haemoglobin, S-ferritin, S-iron, S-transferrin, and transferrin saturation) was evaluated in an epidemiological survey comprising a representative sample of 118 (4%) of the 40- to 49-year-old Faroese male population. All had normal haemoglobin, (mean +/- SD 153 +/- 9 g/l; 9.5 +/- 0.6 mmol/l). Median S-ferritin was 151 micrograms/l, 5-95 percentile 46-588 micrograms/l, observed range 33-1166 micrograms/l. None had depleted iron stores (S-ferritin less than or equal to 20 micrograms/l), 2.5% had 'small' iron stores (S-ferritin 21-40 micrograms/l), 80.5% had 'normal' iron stores (S-ferritin 41 300 micrograms/l) and 17% had 'increased' iron stores (S-ferritin greater than 300 micrograms/l). Transferrin saturation values were greater than 16% in all males; high values greater than 50% were found in 9.3%, and the combination of high transferrin saturation and S-ferritin greater than 300 micrograms/l was found in 3.4% of the males. Median P-ascorbic acid was 26 mumol/l, 5-95 percentile 7-67 mumol/l; significantly higher in subjects taking vitamin supplements (n = 35, median 50 mumol/l) than in those not taking supplements (n = 81, median 23 mumol/l) (p less than 0.0001). There was no correlation between P ascorbic acid and iron status markers. The results indicate a high frequency of ample iron reserves in the Faroese male population. PMID- 2237269 TI - Age-associated decline of hepatic handling of cholephilic anions in humans is reverted by S-adenosylmethionine (SAMe). AB - Decreased fluidity of hepatocyte plasma membrane may contribute to the age associated changes of liver function. This study aimed at investigating whether the hepatic clearance of organic anions declines with age and whether S adenosylmethionine (SAMe), a substance proven to be effective in reversing the age-related decrease of membrane fluidity, might influence this process. Nicotinic acid (NA) half-life and serum bilirubin pharmacokinetics after NA load (5.9 mumol/kg body weight i.v.) were studied in 10 healthy young males (YM) aged 14-28 years and in 10 healthy elderly males (EM) aged 65-81 years, before and after SAMe administration (800 mg/day intravenously for 10 days). At baseline, EM showed serum total bilirubin (STB) levels significantly higher than YM. Similarly, the bilirubinaemic mean curves, STB peak and STB time curve concentration after NA load, expressed as area under the curve (AUC), were significantly higher in EM than in YM (p less than 0.01). NA half-life was also significantly prolonged in the aged group (p less than 0.001). SAMe treatment was followed by a significant decrease of basal STB, STB peak and AUC of STB after NA load in EM (p less than 0.01 vs pre-treatment values) while NA half-life was significantly shortened in both groups (p less than 0.001). As NA and bilirubin share a common carrier protein for hepatic uptake, bilitranslocase, the changes observed in EM may be attributed to the reduced lateral mobility of hepatocyte plasma membrane proteins occurring with age. SAMe, by improving membrane fluidity, may increase the diffusion coefficient of bilitranslocase restoring the hepatic handling of organic anions. PMID- 2237270 TI - Reference intervals for immunoglobulins IgA, IgG and IgM in serum in adults and in children aged 6 months to 14 years. AB - Reference intervals were estimated for immunoglobulins IgA, IgG and IgM in serum in 313 healthy adults aged 17 to 64 years and in 399 children aged 6 months to 14 years. In adults a nonparametric method was chosen for estimating reference interval limits. In children the limits were estimated age-specifically using regression analysis. Immunoglobulin assays used in this study were standardized with a Finnish secondary standard which was calibrated against the World Health Organisation 67/99 immunoglobulin standard. Later, another international primary standard (US National protein standard preparation) was used, the immunoglobulin levels of which are calibrated against the WHO standard. The nominal immunoglobulin concentrations assigned by the manufacturers of several commercial immunoglobulin standard preparations were found to differ from the concentrations measured with the international calibrator used in this study. In conclusion, the reference intervals estimated in this study should be transferable to any laboratory using immunoglobulin assays calibrated against the WHO standard. The usefulness of commercial immunoglobulin standard preparations not calibrated against these primary standards is limited. PMID- 2237272 TI - Horizons in gastroenterology--breaking the barriers. Proceedings of an international meeting held in Port Douglas, Queensland, Australia, 1 to 5 September 1990. PMID- 2237271 TI - Enhanced fractional sodium reabsorption in the ischaemic kidney revisited with lithium as a probe. AB - Extraction of lithium and 51Cr-EDTA across each of the two kidneys was determined during renal vein catheterization in 14 hypertensive patients with unilateral or bilateral renovascular disease before and after i.v. injection of furosemide. Before the administration of furosemide an increased fractional lithium reabsorption was demonstrated across the affected, or more affected kidney. This difference was abolished by furosemide. Using lithium as a probe for sodium, our data suggest an increased fractional tubular sodium reabsorption in the ischaemic human kidney probably located to the proximal tubules as well as to the loop of Henle. Determination of single-kidney fractional lithium reabsorption holds promise as a new research tool for future evaluation of functional abnormalities during divided renal function studies. PMID- 2237273 TI - Inflammatory bowel disease revisited: surgery today and tomorrow. AB - Both topical and systemic medical therapy are helpful in controlling the symptoms in patients with ulcerative colitis. However, no drug therapy is known to influence the natural history of Crohn's disease. Surgical management is often required for the complications of acute colitis unresponsive to medical treatment and for socially incapacitating diarrhoea and urgency due to ulcerative colitis. The gold standard of such surgical treatment is a panproctocolectomy with end ileostomy. In young patients with a good anal sphincter, total colectomy with the formation of an ileal pouch-to-anus anastomosis obliterates the disease and usually results in satisfactory continence. There appears to be no prospect of using gut transplantation in the management of this disease. In the absence of curative medical treatment for Crohn's disease surgical intervention is often needed to control the complications of Crohn's disease. The initial complication that makes the disease symptomatic is stenosis from the healing of asymptomatic ulcers. If strictures can be detected early, they can be treated before secondary complications such as abscess or fistula occur. Some success is being achieved with balloon dilatation of strictures. For the first presentation of ileo-caecal Crohn's disease limited resection offers good long-term cure without the need for continued medical therapy. For recurrent and multiple strictures strictureplasty offers a safe alternative to extensive resection. PMID- 2237274 TI - Alcoholic hepatitis: pathogenesis and approaches to treatment. AB - Alcoholic hepatitis is a necrotizing, often inflammatory, process that is an important precursor to the development of cirrhosis. Acetaldehyde, which is derived from alcohol by the action of alcohol dehydrogenase, is apparently the most important factor leading to alcohol-induced liver injury. Other factors of importance in determining the appearance and rate of progression of liver diseases in patients who are chronic alcoholics include sex, nutritional status, and various immunologic reactions. In addition, there is an incompletely understood genetic predisposition to the development of alcoholic hepatitis. Several histologic features found in patients with alcoholic hepatitis have been evaluated in efforts to determine which are of prognostic value. The predominance of the alcohol-induced injury in zone III of the hepatic lobule; deposition of collagen, IgA, and fibronectin in the space of Disse; defenestration of endothelial cells; and transformation of lipocytes and myofibroblasts to fibroblasts have been investigated. Prolongation of the prothrombin time and marked elevation of serum bilirubin levels are indicators of a subgroup of patients with alcoholic hepatitis who have a poor prognosis, especially if there is also evidence of hepatic encephalopathy. Supportive care and abstinence from alcohol are the foundations of therapy. Corticosteroid therapy appears to decrease the number of early deaths in patients with severe alcoholic hepatitis. Other experimental approaches to therapy include the use of propylthiouracil, anabolic-androgenic steroids, and insulin and glucagon. PMID- 2237275 TI - Epidemiology in peptic ulcer disease. Current status and future aspects. AB - Peptic ulcer incidence is declining. A decreased prevalence of smokers together with other factors have contributed to this change. The widespread use of non steroidal anti-inflammatory drugs (NSAID) has increased the incidence of ulcer in the older population and serious complications, such as perforation and bleeding, have been observed especially in older women. Helicobacter pylori infection is virtually always present in duodenal and gastric ulcer and active chronic gastritis, but not prepyloric ulcer. The fact that this organism is not eradicated with the use of most drugs for peptic ulcer may explain the high rate of recurrence in ulcer disease since relapse rates are reported to be considerably lower when H. pylori is eradicated. In a substantial number of patients peptic ulcers are silent. These fall into two categories: the regular ulcer patient with relapses that heal spontaneously and rarely cause problems, and older patients without prior ulcer disease receiving NSAID treatment, presenting with a life-threatening complication as the first indication of ulcer disease. Despite all the new knowledge of peptic ulcer disease presented, the questions still outnumber the answers; it is therefore suggested that future research focus on the role of NSAIDs and H. pylori. PMID- 2237276 TI - AIDS and the gastroenterologist. AB - Over the next several decades the gastroenterologist practicing anywhere in the world will be confronted with patients with AIDS-related gastrointestinal disorders. Universal body substance isolation precautions should be practiced, however, in dealing with all patients, including those outside traditional 'risk' groups for AIDS. Principal among these precautions are using gloves for personnel involved in procedures and high-level disinfection or sterilization for all endoscopy equipment. Endoscopic procedures should be planned well in advance with special attention to endoscope selection and transport media availability. Organ associated symptoms are reviewed, especially dysphagia, odynophagia, hemorrhage, diarrhea, and abdominal pain. Opportunistic infections and malignancies often present characteristic endoscopic appearances such as that seen for cytomegalovirus ulceration or Kaposi's sarcoma. AIDS-related biliary disorders should also be recognized, principally sclerosing cholangitic or papillary stenosis. PMID- 2237277 TI - Helicobacter pylori: fact or fiction? AB - The recent isolation and classification of the spiral gastric bacteria Helicobacter pylori has led to an explosion of worldwide research. The data strongly suggest that H. pylori is the causative agent for type-B active chronic gastritis. The role of H. pylori in duodenal ulcer awaits clarification, and, more importantly, potential treatment regimens need clear documentation and further detailed research. The past decade has revealed many intriguing facts about H. pylori infection. If, during the 1990s, eradication of H. pylori by means of appropriate and safe medication can lead to the control and prevention of gastroduodenal disease, then major clinical and economic benefits can be anticipated. PMID- 2237278 TI - Screening strategies in gastrointestinal cancer. AB - The concept of screening is based on the notion that regular examination can reduce the mortality from gastrointestinal cancer, but there is as yet little evidence that this is the case in either Barrett's esophagus or ulcerative colitis. Screening is carried out by regular endoscopy with multiple biopsies in an attempt to detect dysplasia, which has traditionally been regarded as the end point of surveillance and the time when resection should be considered. Considerable departure from these guidelines has occurred. Attempts are increasingly being made to select patients in both of these groups who might be at particular high risk of developing dysplasia because of the presence of nuclear aneuploidy, the assumption being that these patients are at particular risk of developing dysplasia and carcinoma. However, data to support stratification at this level are unavailable. In addition, there is not good agreement as to whether surveillance is indicated at all in some groups of patients such as those with less than total colitis or short-segment Barrett's esophagus. The end point of surveillance has also been questioned, with reluctance to recommend colectomy in ulcerative colitis with the finding of low grade dysplasia, possibly because the sampling problem is so great that it may be impossible to confirm that diagnosis on repeated endoscopy and biopsy. While better markers than dysplasia may be required to predict patients at highest risk, there are currently no marker other than the development of invasive carcinoma on which the decision to resect can be based.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237279 TI - Stress ulcers. AB - Gastric stress ulceration occurs rapidly in patients after severe trauma. However, bleeding from stress ulceration is a rare but very serious complication after trauma and major surgery. Important risk factors for stress ulcer bleeding are shock, especially septic shock, and the development of other components of the multiple system organ failure syndrome. The pathophysiology and treatment of stress ulceration is reviewed in this paper. Prophylaxis is the best form of treatment, and the most effective prophylaxis is optimal resuscitation and intensive care. In addition, pharmacologic prophylaxis, including antacids, sucralfate, or acid secretory inhibitors, has been advocated. Once profuse bleeding has started, measures other than aggressive treatment of shock and sepsis are usually unsuccessful. PMID- 2237280 TI - Recent studies of the pathophysiology and diagnosis of esophageal symptoms. AB - The three main symptoms of esophageal disease or disorder are dysphagia, chest pain, and heartburn. Dysphagia in achalasia is mainly due to a non-relaxing lower esophageal sphincter (LES). The mechanism of dysphagia in diffuse esophageal spasm and related motor disorders is related to a combination of several factors including incomplete LES relaxation, failed or weak peristalsis (pressure less than 30 mmHg in the distal esophagus, and orad positive pressure gradient). Meal manometry and balloon distention may prove to be useful provocation tests. Chest pain of esophageal origin may be due to gastroesophageal reflux and esophageal motility disorders; it may also be a manifestation of an irritable esophagus, in which the esophagus is hypersensitive to various stimuli (chemical, mechanical, ischemic). Esophageal provocation tests may suggest the esophageal origin of the pain but do not give information on the nature of the esophageal disorder. Twenty four-hour pH and pressure measurements may, however, yield this information. Heartburn and acid regurgitations are the most typical symptoms of gastroesophageal reflux. Transient relaxations of the LES are considered to be an important contributory mechanism of reflux. Absent basal LES pressure is another mechanism, which accounts for about one-fourth of the reflux episodes in patients with severe reflux esophagitis. During long-lasting inappropriate relaxations, swallows often produce deglutitive contraction waves that die out in the upper esophagus, suggesting that reflux often occurs during periods of inhibition of both LES tone and peristaltic esophageal activity. PMID- 2237281 TI - Where do we stand on gastric motility? AB - This review deals with several aspects of gastrointestinal motility. It attempts to relate basic knowledge to clinically relevant issues. The review is organized around specific contractile patterns and tasks in the gastrointestinal region that are grouped into three broad categories: tonic contractility of the stomach, antral phasic contractility, and resistance of the gastric outlet. There is also a section dealing with the evaluation of gastric motor function for diagnostic purposes describing the technologic means for investigating motility disorders in patients presenting with different clinical syndromes. In this section there is also reference to the criteria to be used in interpretation of the results and practical advice on the use of each test. Finally, the review deals with the issue of treatment of gastric motor disorders, comprising both dietary and pharmacologic approaches. PMID- 2237282 TI - Pressure relationships within the human bile tract. Normal and abnormal physiology. AB - Bile is secreted continuously, although at various rates, from the liver into the biliary tree; whether bile is then diverted into the gallbladder or the duodenum depends on the relative resistance to flow mainly determined by the contractile state of the gallbladder and the choledochoduodenal junction. The resistance of the sphincter of Oddi is considered the principal factor in the regulation of the intracholedochal pressure and, therefore, of the common bile duct-gallbladder pressure gradient; however, filling of the gallbladder may also take place after total sphincterotomy. During late phase II of the interdigestive period intragallbladder pressure increments favour flow of a small amount of bile into the bile duct and, through the sphincter of Oddi, into the duodenum. During phase III of the interdigestive period maximal frequency of sphincter of Oddi phasic contractions blocks bile flow into the duodenum. After a meal tonic active contraction of the gallbladder causes an increase of the intraluminal pressure followed shortly by volume reduction of the viscus and outflow of bile accompanied by an intracholedochal pressure increment. Gallbladder hypotonia is a relevant factor in the pathogenesis of gallbladder stones. The gallbladder acts as a reservoir, since intracholedochal pressure is higher after than before cholecystectomy, and this may explain post-cholecystectomy choledochal dilatation and biliary pain by obstructed bile flow due to either stenosis or dyskinesia of the sphincter of Oddi. PMID- 2237283 TI - Frontiers of biliary endoscopy. AB - The value of endoscopic retrograde cholangiography has been expanded recently by attention to technical detail and new methods for tissue diagnosis. Diagnostic information has been complemented by the new techniques of peroral choledochoscopy and endoscopic ultrasonography. The indications for endoscopic management of bile duct stones have become clearer, especially in patients with the gallbladder in situ. Techniques for distintegration and removal of large stones have improved. In patients with benign and malignant strictures recent emphasis has focused on the role of endoscopic management when compared with percutaneous and surgical approaches. Expandable metal stents are an interesting new option. The latest frontier is the gallbladder, which can now be reached with endoscopic catheters, and even directly with choledochoscopes through the papilla. PMID- 2237284 TI - Non-surgical management of severe chronic pancreatitis. AB - The observation that drainage of the MPD in selected cases of severe chronic pancreatitis has a radical benefit on pain reduction supports the hypothesis that pain is mainly due to obstruction of the MPD. Further follow-up study is needed to assess whether endoscopic management can prevent progression of the disease and especially postpone the onset of diabetes and steatorrhea. The iterative character of the endoscopic management is at least an advantage when compared with surgery, which, in principle, might be considered definitive in only one operation. The present excellent results of non-surgical management of chronic pancreatitis suggest that these new procedures will find a prominent role similar to that already achieved for biliary tract procedures. Therapeutic endoscopy of the pancreas and chronic pancreatitis has focused on the 'stone and stricture' nature of the disease, and techniques have developed accordingly. PMID- 2237285 TI - Etiology of inflammatory bowel diseases: where have we been? Where are we going? AB - The cause or causes of Crohn's disease and of ulcerative colitis remain uncertain. In spite of extensive investigations, searching for immunologic or infectious causes, clear evidence suggesting an underlying etiology is lacking. Recent studies involving mycobacteria suggest that occasional patients thought to have Crohn's disease may indeed be infected with a mycobacterium. However, clear cause-and-effect relationships have not been established. Future efforts at trying to establish the relationship between environmental factors, including infectious agents, and immunologic mediators seem appropriate on the basis of available data. For the present, the causes or cause of these diseases remains obscure. PMID- 2237286 TI - Tumour necrosis factor alpha (TNF-alpha) and interleukin 6 in a zymosan-induced shock model. AB - TNF plays a central role in septic shock induced by endotoxin or Gram-negative bacteria. Zymosan can elicit a septic shock-like syndrome in rodents in the absence of endotoxin. TNF and IL-6 release in mice treated with zymosan was investigated. One hour after intraperitoneal zymosan injection, maximal TNF levels were measured in serum, followed by IL-6 peak levels 1 h later. Treatment with a monoclonal antibody against TNF lowered zymosan-induced mortality from 63 to 11.6%, while maximal IL-6 levels were lowered by about 40%. Mechanisms triggering zymosan-induced cytokine release in murine macrophages were analysed in vitro. Cytokine release was only slightly triggered by uncoated zymosan particles. Thirty-nine per cent of TNF release by macrophages appeared to be triggered by zymosan-bound activated complement. Maximal TNF release also required the presence of natural antibodies against zymosan and zymosan-activated serum. In contrast, maximal IL-6 release was reached upon stimulation with zymosan-activated serum only, while the presence of zymosan particles lowered this response. We conclude that TNF is a crucial mediator in zymosan-induced shock. TNF release can be induced by different immunological pathways, without the need for the direct presence of endotoxins. Although IL-6 release during septic shock is partly dependent on TNF, in vitro trigger mechanisms for IL-6 and TNF differ remarkably. PMID- 2237287 TI - Dynamics of blood components and peritoneal fluid during treatment of murine E. coli sepsis with beta-1,3-D-polyglucose derivatives. I. Cells. AB - Beta-1,3-D-polyglucose derivatives protect mice against otherwise lethal bacterial infections. This protective effect has previously been considered to be mediated through mononuclear phagocytes. We have now investigated the cellular composition in blood and peritoneal fluid after administration of the beta-1,3-D polyglucose before and after challenge with Escherichia coli. In animals treated with beta-1,3-D-polyglucose derivatives, the total white cell number was significantly increased in both blood and peritoneal fluid before and after challenge with E. coli. The increased total cell number was mainly the result of raised levels of granulocytes. The effects of beta-1,3-D-polyglucose-derivatized microbeads (GDM) and soluble aminated beta-1,3-D-polyglucose (AG) were similar. Bacterial counts in peripheral blood in GDM- and AG-treated animals increased with 6 h after challenge and approached zero after 24 h. In untreated animals the bacterial counts increased gradually until the animals died after about 12 h. Bacterial counts in peritoneal fluid of GDM- and AG-treated animals declined to zero after 24 h. In untreated animals there was a slight increase in bacterial counts until the animals died after about 12 h. By using radioactive labelling, we localized the bacterial as well as the beta-1,3-D-polyglucose derivatives during the period following injection. Particle-bound beta-1,3-D-polyglucose was recovered mainly in the milky spots of the omentum. A conspicuous number of bacteria were also recovered in the milky spots. The soluble aminated beta-1,3-D polyglucose was recovered mainly in the liver. However, on a weight basis, the greatest concentration of radioactivity was in the milky spots. PMID- 2237288 TI - Cardiac amyloidosis: report of a patient heterozygous for the transthyretin isoleucine 122 variant. AB - Amyloid fibril material was extracted from autopsy material of a patient who died from progressive cardiac failure at age 64. He had enlarged heart on routine X ray at age 47 and the first symptoms of cardiac failure at age 62. Fractionation of the fibril material resolved peptide fragments immunoreactive with anti-human transthyretin (TTR). One of the peptides was further purified by high-performance liquid chromatography (HPLC) and subjected to tryptic peptide mapping along with TTR isolated from the patient's serum. In both instances, sequencing procedures revealed, in addition to the normal peptide 12 (residues 105-126), an abnormal peptide with an isoleucine for valine substitution at position 122. This substitution has been described previously in a patient with systemic senile amyloidosis (SSA) homozygous for this variant. The results question whether SSA is a clinical entity related to TTR Ile 122 with phenotypic expression in the homozygous condition. PMID- 2237289 TI - Abstracts of papers presented at the twenty-first annual general meeting of the Scandinavian Society for Immunology. Stockholm, Sweden, 11-14 June 1990. PMID- 2237290 TI - [Evaluation of the effectiveness of health care]. AB - During the last two decades, the economic aspects of health care acquired an outstanding attentiveness in all developed countries. Simultaneously, the methods have been searched for a more intensive and perfect application of internal health sources, i.e. manpower, materials and money. New approaches in evaluating health care efficacy (conception of health provision as a branch of national economy) have been made. In accord with them, the efficiency of either individual or partial health actions such as health care programs, preventive measures, diagnostical and curative procedures etc.) is measured. All these questions are the up to date topic for Health care of Czechoslovakia which now is far to dispose of sources comparable with the majority of economically developed countries in Europe. At present, they are approximately similar in supplying 1 person health care needs with 500-1000 dol. a year and even more in several countries, whereas Czechoslovakia spends about 200 dol. on health needs of 1 inhabitant a year. This fact is closely connected with relatively low efficacy of our economy incapable to produce the sufficient sources for providing health care on one hand, and on the other it is due both to the budgetary politics as practiced now and the conception of national product division. The shortage in Health care sources is manifested mainly in retardation of material and technical base of health service altogether with low levelled renumeration of health workers consequential in psychologic, social and political problems. The consequences of this condition are reflected negatively in a level of health service provision. This is as far important as the czechoslovac population health status viewed from the so-called strategic health indices (averaged life expectancy, specific mortality, occurrence of cardiovascular diseases and malignancies etc.) is not favourable due to a number of factors, and its improvement will require considerable efforts from both the health workers and community as a whole. Besides the needful enlargement of sources, these complicated questions are resolvable in observing unity of medical, organizational and economical rationality on all levels of health service management and in all health institutions. This is also the way how to improve the efficiency of health care. The term of efficiency in relation to the health services. In economics, the efficiency is the ratio between the achieved result (effect) and the expenditure of a specified amount of resources. Mathematically, this ratio is expressed as follows: efficiency = end-result/costs Linked to the Health care, the efficiency may be understood also differently from its economic term.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2237291 TI - Laser treatment of recurrent urethral condylomata acuminata in men. AB - Fifty-six consecutive men with recurrent condylomata acuminata of the urethra and possibly also of the external genitalia were treated with carbon dioxide or ND: YAG laser or both. In all patients previous conservative treatments had failed. Half the patients responded completely to a single treatment and 86% to a maximum of three treatments. No important side effects were encountered, and the cosmetic results have been excellent. PMID- 2237293 TI - Laser combined with TURP in the treatment of localized prostatic cancer. AB - Laser treatment associated with transurethral resection of the prostate is a new and promising treatment of the stages T0 diffuse, T1 and T2 prostatic cancer. Our standardized treatment procedure gives few complications. So far we have not recorded any local recurrence in the 26 patients we have treated and followed up from 6 to 42 months. PMID- 2237292 TI - Implantation of beads into the penile skin and its complications. AB - Embedding of beads into the penile skin was observed among 60 foreign workers in the employ of certain Saudi Arabian companies. The procedure had been performed by an unqualified person. They had undergone this procedure in order to increase sexual stimulation of the mate. Infection secondary to implantation procedure had occurred in only 2 cases, necessitating surgical treatment. The first patient was suffering from a penile abscess (one week) after embedding of an ivory bead. The second one was troubled by a painful erection (3 months) after embedding of three glass beads. The other 58 persons had had their implanted beads for varying periods of time, ranging from 3 months to 8 years, without complaint. They refused to have the beads removed. This abnormal procedure is considered to be a manifestation of a suppressed psycho-sexual neurosis. PMID- 2237294 TI - Screening of urinary tract abnormalities among day and nightwetting children. AB - In order to detect possible urinary tract abnormalities among wetters, assessments of previous history completed by ultrasonography of the urinary tract and uroflowmetry were obtained for 145 wetting children and a random sample of 156 sex-matched non-wetting children drawn from a population of 3,375 seven-year olds. Ultrasonography revealed abnormalities, including both morphological ones and cases with incomplete bladder emptying, in 5 out of 73 nightwetters (6.8%, 95% confidence limit, CL, 1.1-12.6), 10 out of 72 day and day and nightwetters (hereafter daywetters) (13.9%, CL 5.9-21.9) and 4 controls (2.6%, CL 0.1-5.0), the figure for the daywetters differing significantly from that for the controls (p less than 0.01). A fractioned voiding curve was recognized in 1 nightwetter (1.4%, CL -1.3-4.0), 7 daywetters (9.7%, CL 2.9-16.6) and 7 controls (4.5%, CL 1.2-7.7) the difference between the nightwetters and daywetters being significant (p less than 0.05). Depending on the previous history and abnormal findings in ultrasonography or uroflowmetry, examinations were continued with intravenous pyelography, voiding cystography, cystoscopy and/or by cystometry. Finally, marked structural or functional disorders of the urinary tract were detected in 11 out of 72 daywetters (15.3%, CL 7.0-23.6), 1 out of 73 pure nightwetters and 1 out of 156 control children. It is concluded that imaging of the urinary tract is not necessary for pure nightwetters, while ultrasonography or uroflowmetry and more sophisticated radiological or urological methods should be focused on those children with daytime wetting and clinical symptoms of voiding disturbances. PMID- 2237295 TI - Local bacillus Calmette-Guerin therapy for superficial bladder cancer: clinical, histological and ultrastructural patterns. AB - The effectiveness of intravesical administration of bacillus Calmette-Guerin as a prophylaxis of superficial bladder cancer has been definitely demonstrated. On the other hand, therapeutic regimens, duration effects, efficacy of either maintenance cycles or repeated courses of therapy in case of failures are still controversial. We report the results achieved in 15 cases of carcinoma in situ of the bladder and in 48 cases of superficial bladder cancer (Ta-T1 stage of disease) with bacillus Calmette-Guerin immunotherapy. Our patients underwent an initial six week cycle and a following maintenance cycle with monthly administrations for one year. Median follow-up was 19 months (range 18-21 months). Patients with carcinoma in situ are now free of disease; on the contrary, patients with Ta-T1 tumors experienced 18 recurrences (28%). There was a marked decrease of recurrence rate when compared to previous local chemotherapy. We report in detail the adverse effects encountered and both histologic and ultrastructural findings observed after immunotherapy. Bacillus Calmette-Guerin therapy can influence positively the natural history of the disease but possible adverse effects should always be considered before starting the treatment. PMID- 2237296 TI - Cisplatin and medium dose methotrexate in advanced transitional cell carcinoma of the urinary tract. AB - Twenty-seven patients with advanced transitional cell carcinoma of the urothelium were studied. The area of each tumour was measured by computed tomography. Twenty four of the 27 patients were evaluated after treatment with the following course of chemotherapy given intravenously: day 1-cisplatin 50 mg/m2; day 2-methotrexate 250 mg/m2; and folinic acid rescue treatment 24 hours after the methotrexate infusion. Each cycle of treatment was given three times, with two weeks between cycles. There were two complete and 11 partial responses, and the primary tumour responded as often as the distant metastases. The toxicity of the regimen was acceptable, even given the advanced age of most of the patients. Most of whom found that their disturbances of micturition and sleeping problems were improved by the treatment. Cisplatin combined with methotrexate achieves a response rate of about 50% in advanced transitional cell carcinoma. When combinations of chemotherapy are being chosen for these often elderly patients the curability and palliation effects must be balanced against the toxicity and morbidity. PMID- 2237297 TI - Results of 5,035 stone analyses: a contribution to epidemiology of urinary stone disease. AB - Between 1978 and 1988 5,035 urinary calculi have been analysed by X-ray diffractometry. 1,615 of these stones have additionally been investigated by scanning electron microscopy (SEM). The overall sex-ratio was 1.86 (m/f). Ca stones and uric acid containing stones are more frequent in male patients (m/f = 2.08 and 3.86, respectively) whereas infection stones and cystine stones show a higher rate of appearance in female patients (m/f = 0.6 and 0.88, respectively). The percentage of open surgery ranged about 30% in the first few years but decreased to 5-7% in the last few years due to the new methods of stone removal. The rate of occurrence of the crystalline phases does not differ remarkably from other statistics except for a higher incidence of apatite because of the high sensitivity of detection of this phase by SEM. The recurrence rate of brushite stones amounting to 66.7% is very high and exceeds even that of cystine stones (60.7%). PMID- 2237298 TI - The role of hyperoxaluria in the formation of calcium oxalate urinary calculi, and its association with other biochemical measurements. AB - The part played by hyperoxaluria in the formation of calcium oxalate urinary calculi was studied in 153 patients who had each been diagnosed as having calcium oxalate urinary calculi on one or more occasions. Seventy-seven of the patients excreted normal amounts of calcium (less than 6.2 mmol/d), and 76 had hypercalciuria (excretion greater than or equal to 6.2 mmol/d); each group was divided into a further two groups depending on whether the oxalate concentration was above or below 0.16 mmol/l. Pure calcium oxalate stones were more common in patients whose calcium excretion was normal, and mixed calcium oxalate and phosphate stones were more common among hypercalciuric patients. Urinary concentrations/day of magnesium, citrate, and phosphorus were significantly lower in the two groups in which the oxalate concentrations were below 0.16 mmol/l than in a normal control group, and magnesium and phosphorus were significantly lower in the two groups in which oxalate concentrations were less than 0.16 mmol/l than in the two in which they were above that value. The concentration of citrate was also lower, but not significantly so. In addition, the pH of the urine in patients with mixed stones was significantly higher in all groups than when the stones were composed of pure calcium oxalate. PMID- 2237299 TI - Urinary tract calculi dissolved by means of renacidin. An experimental study. AB - Removal urinary tract calculi by surgery may be difficult in patients with poor health or in patients who have been operated on earlier. By means of percutaneous nephrostomy it is possible to irrigate the renal pelvis with Renacidin to dissolve calculi. Renacidin is a buffer and mainly consists of citrate and gluconate. The solution makes it possible to dissolve some calculi. This study was carried out in order to evaluate the influence of the concentration of renacidin and of the speed of the irrigation. Urinary tract calculi were obtained from five patients. The calculi were cut into 2 mm thick slices. Each slice was weighed before it was placed in a chamber for irrigation. Irrigation of the slices by means of renacidin was performed at speeds of 30, 60 or 120 ml/h. Slices wre also kept in vessels containing renacidin without replacing the fluid during the irrigation. In two series dissolution was investigated for various concentrations of renacidin. Elementary analysis using absorption and spectrophotometric techniques was performed and a qualitative evaluation of the distribution of the inorganic components was carried out using the microradiographic technique. The speed of the dissolution of urinary calculi varied between 0.43 and 7.7 mg/h. Two stones were easily dissolved (5 and 7.7 mg/h) while the three others were more resistant (0.5, 1.0 and 3.0). Diluted renacidin fluid (1:3) was less effective and reduced dissolution from 5.8 to 0.7 mg/h. The speed of the irrigation was of minor importance in the experimental situation. The dissolving effect of renacidin varied for different calculi.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237300 TI - Hemodialysis does not always protect against recurrence of Wegener's granulomatosis. AB - Hemodialysis may protect against disease activity in Wegener's granulomatosis. We report here a 41-year-old woman with Wegener's granulomatosis, in whom renal transplantation was performed after a 10-month period of hemodialysis during which no signs of disease activity were detected. Recurrence of disease did, however, take place 2 years after renal allograft transplantation despite immunosuppressive therapy with cyclosporine A and prednisone. Reinstitution of hemodialysis and graftectomy did not improve the patient's condition but plasmapheresis and treatment with cyclophosphamide and prednisone eliminated all signs of disease within a fortnight. A proposal for better maintenance of these patients is made. PMID- 2237301 TI - Primary renal non-Hodgkin lymphoma. AB - Two cases of primary renal non-Hodgkin lymphoma are presented. Clinical and pathologic characteristics and diagnostic aspects are discussed. Radical nephrectomy followed by chemotherapy is the treatment of choice. New chemotherapy patterns have improved the prognosis. Although rare, non-Hodgkin lymphoma should be included in the differential diagnosis of space-occupying renal lesions. PMID- 2237302 TI - Amatoxin intoxication. AB - Ingestion of mushrooms followed after 6-12 hours by gastrointestinal symptoms and after 3-4 days by hepatic symptoms is diagnostic for the life-threatening amatoxin intoxication and should be treated as soon as possible. Four case histories are reported and recommendations for treatment are given. PMID- 2237303 TI - Huge renal angiomyolipoma presenting with bleeding in a 76-year-old woman. Case report. AB - Renal angiomyolipoma is a rare, benign and hypervascular tumour. Its symptoms may be acute, with severe bleeding, or protracted, few and recurrent, due to bleeding and pressure. A symptomatic case is presented. The patient seems to be the oldest on record, and with the longest-lasting symptoms and the biggest tumour. PMID- 2237304 TI - Vaginal metastasis as the first sign of renal cell carcinoma. A case report and review of the literature. PMID- 2237305 TI - Calciuria in Bartter's syndrome. PMID- 2237306 TI - Autotransplantation of lymph node fragments. Structure and function of regenerated tissue. AB - In pigs slices of autologous lymph nodes were implanted in the subcutaneous fat, under the muscular fascia or under the kidney capsule to study the regeneration of autotransplanted lymph node tissue. The regenerated nodules consisted of all the normal compartments found in lymph nodes and there was evidence that afferent lymphatics reached these nodules. Superficial inguinal lymph nodes regenerated more often and with a better structure than mesenteric lymph nodes. The sites under the kidney capsule and the fascia of muscles were found to be a less stimulating microenvironment for regeneration than the subcutaneous tissue. Regeneration of transplanted lymph node tissue was observed in pigs which had been operated on as young piglets or as adults. The regeneration of autotransplanted lymph node tissue might be a useful model for draining lymphedema, especially from the extremities. PMID- 2237307 TI - Effect of bleeding and hypervolaemic haemodilution on traumatic vasospasm in rabbits. AB - The effect of bleeding (20% of total blood volume) and of hypervolaemic haemodilution with dextran infusion (20% of total blood volume) on traumatic vasospasm was studied in the central ear arteries of 10 rabbits. The blood pressure dropped significantly after bleeding and the packed cell volume was significantly lower after dextran infusion. Neither treatment had any effect on the duration, intensity or severity of the vasospasm. The results suggest that moderate changes in blood volume do not influence traumatic vasospasm. PMID- 2237308 TI - The palmar digital venous anatomy. AB - Fresh human cadaveric hands were injected with a liquid plastic polymer and dissected under the operating microscope. On the palmar aspect of the digits, four different venous patterns could be identified, characterized by their tributaries and branching pattern, and by the presence, position and direction of valves. Arborized veins drain a limited volume of tissue by a number of very slender vessels that come together to form a common trunk. Venous arches are found both superficial and deep, palmar and lateral; they neither branch nor have valves, except at both ends. Deep axial veins accompany the digital arteries as comitant veins. They drain to both the metacarpal comitant veins and the web space veins. Superficial axial veins run principally in the subdermal layer of the finger; they drain either directly to dorsal veins or to the natatory vein on the ligament of the same name. PMID- 2237309 TI - Superficial venous anatomy of the human palm. AB - In a study of the venous anatomy of the palm, a high degree of consistency has been found in the organization of the superficial vessels, which lie between the palmar fascia and the dermis. Although in the superficial palm, as previously reported for the fingers, there are large individual variations in the detailed topography, the basic functional venous anatomy remains highly consistent. The present paper demonstrates the findings from dissections of 12 human cadaver hands after injection of a polymerizing plastic solution into the vascular tree. The basic types of superficial venous structures found in the superficial palm are presented, and their functional importance for the drainage of blood from the palm is discussed. PMID- 2237310 TI - Effects of electrical nerve stimulation (ENS) in ischemic tissue. AB - Blood flow was measured in the skin flaps of 20 patients who had undergone reconstructive surgery. All flaps were showing clinical signs of deficient circulation. Local blood flow in skin flaps was significantly increased by electrical nerve stimulation (ENS) (p less than 0.001), but not by placebo ENS. Repeated ENS treatment reduced stasis and oedema significantly (p less than 0.001), and the capillary refill was also significantly improved (p less than 0.001). PMID- 2237311 TI - Tissue expansion and skin circulation. Simultaneous monitoring by laser Doppler flowmetry and transcutaneous oximetry. AB - The skin circulation was examined in nine patients during filling of their breast expander prostheses. Despite the high expansion pressure, which was increased above the systolic blood pressure, the overlying skin showed good circulation both clinically and when measured with a laser Doppler flowmeter and a transcutaneous oximeter. We conclude that the expansion was therefore directed to the tissues between the expander and the skin--that is, the fibrous capsule surrounding the prosthesis. Nine subcutaneous tissue expanders located in different anatomical regions were overfilled to a pressure at which all skin circulation ceased. Sufficient saline was then removed to allow skin circulation to return. Oxygenation of the skin ceased at a relatively low pressure when measured by transcutaneous oximetry, whereas when the skin circulation was measured with a laser Doppler flowmeter it did not disappear until the expander pressure had been raised appreciably above that level. PMID- 2237312 TI - Cleft lip and palate patients prior to delayed closure of the hard palate: evaluation of maxillary morphology and the effect of early stimulation on pre school speech. AB - Speech and maxillary development were analysed in two groups of patients with unilateral cleft lip and palate; both groups had early jaw orthopaedic treatment and a surgical regimen that included two-stage lip surgery (mean ages of 2 and 19 months) and soft palate repair (8 months). Closure of the hard palate was postponed until the children were 8 to 10 years of age. The first group comprised 10 consecutive patients who were analysed at 5 and 7 years of age, and the second group seven patients who were studied at the age of 5. Both groups were thus investigated before the repair of the cleft in the hard palate. In addition to surgical and jaw orthopaedic treatment, the second group of patients received early stimulation of lip and tongue tip movements. Our results indicated that hypernasality was less a problem than was retracted palatal or velar articulation of dental consonants. These deviations tended to be reduced, however, after early stimulation. There seemed to be no clear association between the size of the residual cleft in the hard palate and the extent of speech development. The average size of the residual cleft in our patients was comparatively small, and decreased further during follow up. We conclude that preschool children with unilateral cleft lip and palate may develop good speech, in spite of the residual cleft, if they use an intraoral plate and are given extra lip and tongue tip stimulation, together with early speech therapy if necessary. PMID- 2237313 TI - Closure of the cleft palate in one or two stages: the surgical methods. AB - The details of two consecutive groups of cleft palate patients treated with one- or two-stage palate repair are presented. The total number of patients is 237, with 128 operated in one stage, and 109 operated in two stages. In the two-stage group, the frequency of 'unintended' palatal fistulas decreased by 80%, and the use of blood transfusions was greatly reduced, but total operation time and hospital stay were longer. The results in terms of speech quality, facial growth and dental occlusion, will be reported on separately. PMID- 2237314 TI - Reactivity of the microcirculation in port wine stain hemangiomas evaluated by laser Doppler fluxmetry. AB - Twelve patients with port wine stains (both untreated and treated with argon laser) had their microcirculation monitored by laser Doppler flux at rest and after arterial occlusion lasting one minute. The blood cell flux was measured in normal, untreated and treated skin areas. The resting flux was significantly higher in untreated port wine stains than in the normal skin. The reactive hyperemia response was significantly impaired in the untreated skin, although a 60% increase in blood cell flux was achieved by the short arterial occlusion. In most of the recorded parameters the treated areas showed a less pathological reaction than the untreated ones. We conclude that peroperative vasodilation can be induced in port wine stains, and this may be used to improve the outcome of argon laser treatment. PMID- 2237315 TI - Gustatory rhinorrhea after radical parotidectomy. AB - A man of 63 developed unilateral gustatory rhinorrhea shortly after radical parotidectomy for infiltrating squamous cell carcinoma that had metastasised to the parotid lymph nodes. There is a similarity between this condition and the gustatory vasodilatation and sweating of Frey's syndrome, but despite circumstantial evidence that misdirected nerve regeneration causes these symptoms, their exact aetiology is still unknown. PMID- 2237317 TI - Isolated compression of the motor branch of the median nerve by a ganglion. Case report. AB - A 25-year-old hairdresser presented with a fluctuant lump in the palm of her right hand that was intermittently painful and made control of her right thumb difficult. She had no sensory loss. At operation a cystic swelling was found 8 mm in diameter distal to the carpal ligament and compressing the median nerve. The cyst ruptured during dissection, and it was not possible to localise the pedicle. Histological examination showed that it was a ganglion, and nine weeks after the operation the patient had regained normal use of her hand and resumed her work. PMID- 2237318 TI - Aneurysmal bone cyst of the hand. An unusual location in the first phalanges of the first finger. Case report. AB - A 40-year-old woman presented with a lesion on the first phalanx of her right thumb, which on radiography appeared to be a cystic lesion. This was treated with curettage and bone graft but recurred a year later. It was treated in the same way, and 18 months later there has been no sign of recurrence. Histological examination confirmed that it was an aneurysmal bone cyst. PMID- 2237316 TI - Closed longitudinal splitting of the carpus. Case report. AB - Closed longitudinal splitting of the carpus is a rare injury with disruption of the transversal carpal arch. One case with a stroke injury is reported; the injury was work-related and occurred as a broad stroking injury to the volar side of the right hand and wrist. The patient was treated with open reduction, ligament repair and percutaneous pinning of a wide diastasis. Despite the return of wrist motion, pinch and grip strength remained below normal at follow-up examination. There appears to be a weak point between the capitate and hamate and the third and fourth metacarpals. PMID- 2237320 TI - Perichondrial grafting for total replacement of the patella. Experimental study in rabbits. AB - In five adult rabbits excision of the patella of one knee joint was carried out. The defects were reconstructed with free grafts taken from rib perichondrium. After survival times of 2.5 and 5 months, neocartilage was seen in all grafts on histological examination. In three of the five, the central part of the reconstructed patella showed bone formation. PMID- 2237321 TI - Strategies in the education of humane physicians. AB - Various reforms to change the character of medical education have been implemented since the 1960s at American medical schools. The public demand for a more "humane" physician resulted in the incorporation of new sciences in the medical curriculum--behavioral sciences in the 1960s and 1970s and humanities in the 1980s. It is argued that broader structural changes in the American health care system underlie the need for these educational reforms, which in practice allow the medical profession to maintain its autonomy and control over its work. For comparison the curricular innovations in medical education in the Nordic countries are examined. PMID- 2237319 TI - The effect of growth factors and synovial fluid on chondrogenesis in perichondrium. AB - Reconstruction of cartilage with perichondrium depends on the chondrogenic property of the perichondrial fibrocytes. The present investigation concerns the conditions for the differentiation of fibrocytes into chondrocytes both in vivo and in vitro. For the in vivo studies specimens of rib and auricular perichondrium from adult rabbits were wrapped round silicon rods which were enclosed in dialysis bags. One was placed in the suprapatellar pouch of the knee joint and one was placed intraperitoneally in each rabbit. After two months the bags were extracted, the perichondrium prepared for microscopic examination, and the chondrogenesis evaluated. In vitro the perichondrium was divided into small pieces and incubated with tissue culture medium. The medium was supplemented with fetal calf serum, together with epidermal growth factor, platelet derived growth factor, synovial fluid, or with human serum albumin (control group). After three weeks the explants were prepared for microscopy. Chondrogenesis was judged by the degree of cellular enlargement, capsule formation, deposition of matrix, and activation of the outer fibrocytic layer. In vivo, good cartilage development was found in all specimens placed in the knee joint but, in those placed intraperitoneally, little if any chondrogenesis was seen. In vitro profound differentiation occurred in all cultures supplemented with epidermal growth factor and platelet derived growth factor. An equivalent differentiation was found in perichondrium that had been incubated with synovial fluid. We conclude that the differentiation of perichondrial fibrocytes is initiated in vitro by growth factors. In addition, we have shown that synovial fluid contains factors that promote and enhance the development of cartilage from perichondrium. PMID- 2237322 TI - Simply osteoporosis--or multifactorial genesis for the increasing incidence of fall injuries in the elderly? The need for a scientific approach to reducing injuries. AB - Both the high and rising incidence of injuries in old age and a situation where accidents are looked upon as "super-human" events, impossible to prevent, call for a scientific approach to the problem. Another strong reason for stressing the scientific approach is the complex aetiological origin of injuries in the elderly. Individual factors as well as factors overrepresented in the injured population must find a developed model as site for their importance compared to agent factors and environmental factors. If not, there will be an everlasting contradiction between the discussion on monofactorial "causes" of injuries like osteoporosis, lacking physical exercise, environmental risks, etc. Still another reason is that the present serious situation with an increasing incidence of injuries in the elderly call for urgent preventive programmes as well as development of operation methods, rehabilitation methods and environmental changes. Unfortunately, in spite of the importance and magnitude of the number of injuries as a public health problem, relative little scientific attention has been given to the area of injury control. In the paper it is concluded that there is a need for model development. These models should combine an epidemiological approach with a behavioural scientific method as well as a system-oriented model. Such models are available in occupational injury prevention and should as well be tested in prevention of injuries in the elderly. PMID- 2237323 TI - Varicella among immigrants from the tropics, a health problem. AB - The incidence of varicella in Tamil refugees in Denmark was evaluated. Of 256 Tamils, 44% developed varicella infection in the first few months after arrival, representing 38% of the adults, and 68% of the children. During approximately four months' observation in Denmark, 75% of the refugees with no history of varicella developed a typical infection whereas only 2% of those with a history of varicella developed the disease. Tropical refugees with a negative history of varicella must therefore be considered nonimmune. Nine of 44 fertile women were pregnant. Two acquired the varicella infection during the first-trimester, none in relation to delivery. By organizing a health-check on arrival, prophylactic measures can reduce the health hazard of varicella infection in refugees from the tropics. PMID- 2237324 TI - Salmonella and Shigella carriers among refugees from the middle east and Sri Lanka in Denmark. AB - One per cent of ten thousand refugees were asymptomatic carriers of Salmonella and Shigella species found by a differentiated health check programme at a Danish Red Cross arrival centre in Denmark 1985 and 1986. Six patients with typhoid fever and one with S. parathyphi-A septicaemia all fell ill within the first few weeks after arrival. A child of a chronic S. typhi carrier developed typhoid fever four months after arrival. Cases of sporadic and mild diarrhoea occurred due to Salmonella and Shigella species. The carriers were instructed in prophylactic, hygienic measures and no outbreaks developed. The health check system in this period seemed to be sufficient in relation to preventing outbreaks of infections caused by non-typhoid Salmonella and Shigella species. The relative cost-effectiveness of a more intensive S. typhi screening on arrival is questionable. The organization of health check systems should be reviewed regularly, as each refugee situation is different and will change in different periods. PMID- 2237325 TI - Work and "lifestyle" in occupational mortality in Denmark. AB - Using social class standardization Fox and Adelstein found that 18% of all mortality was attributed to work, while 82% was attributable to lifestyle. Fox and Adelstein had access to 25 occupational orders. We have made similar calculations on Danish mortality statistics including 146 occupational groups. Our results are very different: more than 50% of all mortality among Danish men seems to be related to work. Of 51,317 work-related deaths in 10 years, one third were due to cancer, and half due to cardiovascular diseases (CVD). The marked differences in results have lead to considerations on the applicability of the model and the underlying assumptions. One conclusion is that social differences and differences in mortality between social groups are so small in Denmark that a few subgroups with "deviant" mortality and/or lifestyle will be determinants of the results. Inclusion of more occupational groups increases the percentage of deaths associated with work. PMID- 2237326 TI - The penetrating educational effect of a mass-media based fund-raising campaign "heart for life". AB - A one-Sunday fund-raising TV-show in 1987 was broadcasted by the state-owned TV channel in Norway which is the only channel covering the whole country. The six hour TV-show consisted of a considerable amount of information on risk of heart disease intermingled with entertainment and money-counting results. Mass media had covered the forthcoming TV-show extensively. The show is presently evaluated as a nationwide mass-media based health education campaign through a stratified random sample of 976 persons aged 15 years and above. More than 95% of the population were aware of the campaign and 75% followed the TV-show beyond the news reports. The sampled persons were asked for self-reported changes in health knowledge and behaviour. Fifty-seven per cent reported that they gained new knowledge and 25% reported behaviour changes in a positive direction. Women reported more knowledge gain than men. Low socioeconomic groups reported more gain in knowledge and more positive changes in health behaviour than high groups. A close association was found between reported new knowledge and change of health behaviour (p less than 0.001). The results of the study indicate that this campaign has reached segments of the population that previously have been difficult to reach and that this is possibly due to the extensive advance coverage of the show in the mass media and the "entertaining" character of the show with emotional appeals in addition to factual information. PMID- 2237327 TI - Illness behaviour in mental ill-health in Kuwait. AB - Two hundred and eight individuals were interviewed in order to study the behaviour they adopt in relation to the most common somatic and emotional symptoms of mental ill-health. Illness behaviour included ignoring, brooding, self-help and consultation of others. Older individuals tended more frequently to resort to meditation, native healers and doctors. Males consulted doctors more than females. Brooding was more frequent in well educated subjects. A group of married expatriates who left their wives in their original countries were the most likely to consult doctors. Education and marital status were the most predictive of brooding and self-help behaviour. Self-help was the most commonly adopted illness behaviour. The results are explained in terms of the social and cultural background of the individuals studied because this influences their methods of expressing distress and their action in relation to symptoms. PMID- 2237328 TI - Social conditions of children born after artificial insemination by donor. AB - Few objective data are available concerning the social conditions of children born after artificial insemination by donor (AID). We have studied 341 consecutive AID children born of 261 women during a 13-year period. Data from hospital archives were compared with information from the National Register of Norway. The parameters studied included age-relations of parents and offspring, sex- and age-relations between siblings as well as the divorce rate in AID families. Median maternal age at birth of the first AID child was 30 years. Forty three percent of AID children were born in families that already had children or that later obtained an additional child; the majority of these siblings were conceived by AID. Mean age difference between the closest related AID siblings was three years. Six of the 261 AID families were split by divorce during the study period. The results only reflect such information as can currently be obtained with maintenance of the promise of secrecy. PMID- 2237329 TI - Male partners in infertile couples. Personal attitudes and contact with the Norwegian health service. AB - The present study summarizes the results of a questionnaire sent to 312 men involved in a fertility investigation. The answers illustrate the psychological problems linked to the infertile state, indicate that men are generally well orientated about the extent of the problem and imply an increasing negative attitude to donor insemination. In the majority of cases, the infertile couples first contacted a gynecologist rather than a general practitioner or other specialist. In over one third of the cases, this contact occurred within the first 12 months of attempting to procure a pregnancy. In most cases, the male partner was already involved in the fertility investigation at the start. Approximately one fifth had at some time consulted fringe medicine (e.g. homeopathy or acupuncture). PMID- 2237330 TI - Premature deaths among men in a Swedish municipality--civil status and primary health care utilization prior to death. AB - Causes of premature deaths among men in relation to civil status and primary health care utilization were studied in a Swedish municipality. Alcoholism, suicide and accidents (psycho-social deaths and accidents) were of special concern (40% of all deaths). When principal and contributing causes of death were considered, alcoholism was registered in 21% of all men. Including information from primary health care records, the Social Services and the local outpatient alcohol clinic, the proportion of men with alcohol abuse was 40%. Half of the men with psychosocial deaths and accidents were divorced at the time of death. The time elapse between divorce and death was especially short for those who committed suicide, 1.4 years, compared to 9.5 years when death was due to alcohol. Half of the men who visited the primary health care centre six months before death were single, and the problem of the final antemortem visit anticipated the cause of death in the majority of these men. PMID- 2237331 TI - A trial that failed, and the reasons why: comparing the Minnesota model with outpatient treatment and non-treatment for alcohol disorders. AB - A randomised clinical trial was conducted in order to compare treatment results between Minnesota model treatment for alcohol abuse and outpatient treatment. The trial had to be discontinued due to problems in recruitment of subjects and a high rate of attrition among subjects allocated to Minnesota model treatment. In this paper the problems encountered during the trial are discussed. Different methods of recruitment of subjects to a randomised trial are compared. PMID- 2237332 TI - HIV infection and health personnel: health care workers' opinions concerning some ethical dilemmas. AB - A survey was made of a sample of 359 Norwegian health workers to assess attitudes towards HIV infected colleagues, and how the respondents would behave if they themselves became HIV infected. Two thirds of the 268 (75%) who responded would not allow that a HIV positive health worker treated their family, and 47% supported routine HIV screening of health workers to protect patients. Most of the respondents were opposed to disability pensioning of HIV infected health personnel in general, and would not ask for this if were found HIV positive. One hundred ninety-six would not tell colleagues if they became HIV infected. Within this group, the proportion (153/196) that would not accept practising HIV positive health personnel was significantly larger than that among those who would report own seropositivity (24/64). The study revealed substantial anxiety, and inconsistencies between expected behaviour of others, and the respondents' own reactions also were found. PMID- 2237333 TI - Survival of AIDS patients in Norway. AB - The survival function of the 100 first AIDS patients in Norway is presented and analyzed with respect to four factors obtained at the time of diagnosis; a) year of diagnosis b) initial AIDS related disease c) knowledge of HIV seropositivity prior to onset of AIDS and d) age at time of diagnosis. The median survival was 9.3 months. Among the known seropositive AIDS patients there were almost twice as many with Pneumocystis carinii pneumonia as initial AIDS related disease, as among the not known seropositives (relative risk 1.8). With Cox regression analysis we found that known seropositivity and age are factors that appear to influence survival, whereas year of diagnosis and initial AIDS related disease apparently do not. The mechanism whereby prior knowledge of HIV seropositivity leads to apparent increase in survival may be due to better follow-up and thereby an earlier date of diagnosis. PMID- 2237335 TI - [Nutrition in the first days of life: how many infants need supplemental food?]. AB - A prospective study of 280 consecutive newborns (birth weight greater than 2500 g) showed that on discharge from hospital 88.5% were fully and 8.6% partly breastfed. Only 8 children (2.9%) were weaned. In the group of the fully breastfed infants, 8.5% received no prelacteal food or fluid, 85.9% received a 10% dextromaltose (DM) solution and in only 5.6% of the children was there additional feeding with an adapted milk formula for some days. This restrictive attitude concerning supplemental feeding involved no observable drawbacks. The increasing incidence of atopic diseases--especially cow's milk allergy, the evolution of which is essentially promoted by the administration of foreign proteins in the first days of life--justifies a feeding policy on these lines. The elimination of bovine proteins in the newborn period is of considerable preventive significance. On the other hand, restriction of water supply (10% DM solution) is not advisable in our opinion. PMID- 2237334 TI - Occupational cancer in Denmark. Cancer incidence in the 1970 census population. AB - Data sources and creation of data files. The cohort of persons who were 20-64 years of age at the time of the 1970 census has been followed for cancer incidence for a ten-year period. The study was made by linkage of individual records from the 1970 census, the Central Population Register, death certificates, and cancer registrations. Data were included on individual characteristics recorded in the census on prevalent cancer cases at the time of the census and on deaths, emigrations, and incident cancer cases during the ten year follow-up period. The study includes a total of 2.8 million persons, of whom 2.0 million were economically active at the time of the 1970 census. A total of 115,000 incident cancer cases were registered during the follow-up period, and 77,000 of these occurred in persons who were economically active in 1970. The classifications used in the census included 218 codes for occupation and 245 codes for industry. The Cancer Registry data included 639 codes for diagnosis. Cancer incidence by social groups in Denmark. The cancer incidence was tabulated across 32 socioeconomic groups for 43 cancer sites among the men and 45 cancer sites among the women. The study showed an almost twofold difference in the overall cancer incidence between the socioeconomic groups of the men. Self employed farmers were at low risk (RR 0.68), and unskilled workers in shipping/fishing were at high risk (RR 1.28) when the cancer incidence among all economically active men was used for the comparison. The social pattern in cancer incidence correlated well with the pattern for cancer mortality among men. As a rough estimate, the cumulative incidence for all cancer among persons under 75 years of age could be reduced by 32% if all Danish men had the cancer incidence of farmers. There was a fivefold or larger difference between the socioeconomic groups in the incidence for nine cancer sites. These nine cancer sites together represented 7% of the cumulative incidence for all cancer. Estimated in a similar way, the cumulative incidence could be reduced by 44% if all Danish men had the site-specific cancer incidence of the respective low-risk groups. The overall cancer incidence among the women varied from a relative risk of 0.71 for unskilled workers in agriculture to a relative risk of 1.18 for self-employed women in other industries I (dentists, lawyers, etc) when the cancer incidence among all economically active women was used for the comparison.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2237336 TI - [Cardiac complications of American trypanosomiasis (Chagas disease). Various case reports and general observations]. AB - Three young female patients with heart problems and positive serologic tests or characteristic histologic lesions for Chagas' disease (American trypanosomiasis) are reported, one of them having presented with acute anterior myocardial infarction with only minor coronary lesions. The most prominent features of the disease are discussed with emphasis on late cardiac complications. Chagas' cardiomyopathy is the leading cause of sudden death in Latin America, where an estimated 10 to 12 million people are infected in endemic areas from southern Mexico to southern Argentina. It has also been termed "emboligenic cardiomyopathy" since arterial embolism is a very frequent complication. Embolic obstruction of a coronary artery may therefore well be the most probable cause of myocardial infarction in young people with Chagas' disease, although other mechanisms cannot be excluded. PMID- 2237337 TI - [Particle retention in the intrapulmonary conducting airways in hamsters]. AB - Inhalation and the subsequent deposition, retention and clearance of particles play a pivotal role in pulmonary medicine. It has been widely accepted that inhaled insoluble particles which are deposited in the conducting airways are largely cleared within 24 hours by the mucociliary escalator. Recent reports, however, suggest that this view should be revised. We therefore investigated by light and electron microscopy the number and location of particles retained in the intrapulmonary conducting airways of hamsters as a function of time. The number of retained particles was estimated unbiasedly with a novel stereological method, the fractionator. Seven male Syrian Golden hamsters inhaled an aerosol of 6 microns polystyrene particles under controlled conditions. The lungs of 3 animals were fixed by intravascular perfusion 20 minutes after the inhalation, whereas those of the other 4 animals were fixed 24 hours later. Retained particles were found in all generations of the intrapulmonary conducting airways. They were submerged in the extracellular matrix in close contact with the epithelial cells between the cilia. The particles were coated by a thin layer of osmiophilic material which was interpreted as surfactant. In the lungs fixed immediately after the inhalation, 36% of the retained particles were ingested by macrophages. 24 hours after inhalation we still found 14% of the initially retained particles. 90% of these remaining particles were phagocytized. We conclude that: (1) Surfactant is important for the retention of particles in the intrapulmonary conducting airways of hamsters. (2) There is evidence for the existence of a resident population of very active airway macrophages which play a pivotal role in clearance of the retained particles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237338 TI - [Reversible ophthalmoplegia, cerebellar syndrome and vigilance disorders following phenytoin poisoning]. AB - A 20-year-old man developed marked ophthalmoplegia and cerebellar symptoms after suicidal intoxication with phenytoin (maximal plasmatic level 73.6 mg/l). Symptoms of toxicity completely resolved with supportive care and with activated charcoal. The clinical picture of acute phenytoin intoxication is reviewed. The most common disorders are ataxia, nystagmus and mental status changes, but ophthalmoplegia is rare. PMID- 2237339 TI - [Epilepsy and pregnancy]. AB - Epilepsy affects almost 1% of all pregnant women. The effect of pregnancy upon epilepsy is unpredictable for the individual patient. In one third to one half of the patients epilepsy had no effect on seizure frequency, in one fourth to one third of the patients seizure frequency increased, and in one third to one fourth it improved. Several reasons are discussed for a frequently observed tendency to a drop in plasma concentration of antiepileptic drugs during pregnancy where the daily dose was kept unchanged. For unknown reasons, perinatal lethality is up to twice as high as in controls. The risk of bearing children with malformations is approximately 1.5-3 times higher for mothers with epilepsy than in non-epileptic mothers. Apart from antiepileptic drugs the role of genetic factors, the type and severity of epilepsy and the possible influence of grand-mal seizures during pregnancy must be considered to be involved in congenital anomalies. Polypharmacy produces more frequent anomalies than monotherapy. Valproate should be avoided in the pregnant women due to the increased incidence of neural tube defects. At this time there is no reason to discourage a mother on antiepileptic drug therapy from breast feeding. PMID- 2237340 TI - [Physiopathological basis of protection of the ischemic myocardium]. AB - Ischemia initiates a cascade of intracellular events that culminates in the death of the myocyte. Reperfusion of ischemic myocardium is the most efficient way of salvaging jeopardized cells. Additional measures referred to as "myocardial protection" may further reduce ischemic injury, primarily by delaying the progression of cellular damage during ischemia. The pathophysiological aspects of ischemic injury and the possibilities for protection of ischemic myocardium are reviewed. In addition to the "established" methods of myocardial protection, the concept of prevention of "reperfusion injury", presently under experimental investigation, is discussed. PMID- 2237341 TI - Recent advances in myocardial protection using antegrade/retrograde blood cardioplegia. AB - This presentation details techniques of delivery of antegrade/retrograde blood cardioplegia to ensure its distribution to prevent ischemic damage during aortic clamping, and describes methods of using warm blood cardioplegia to "resuscitate" the heart when used to induce cardioplegia and "avoid reperfusion damage" when given just before aortic unclamping. A technique of rapid transatrial cannulation of the coronary sinus is described to permit safe, rapid, and simple use of retrograde cardioplegia and avoid right heart isolation. Theoretic objectives of these operative techniques are discussed, together with presentation of the specific methods of achieving the aforementioned goals of using blood cardioplegia for resuscitation, prevention, and avoidance of ischemic and reperfusion damage. The preliminary clinical experience with antegrade/retrograde cardioplegia is summarized, and these results have led to adoption of these techniques of blood cardioplegia as the preferred method of myocardial protection in all adult operations and in many pediatric cardiac procedures. PMID- 2237342 TI - [Cardiopulmonary resuscitation in Switzerland: time to act!]. AB - Cardiovascular related deaths still represent about 50% of all demises despite their decreasing incidence in the United States and in Switzerland. About two thirds of these deaths are due to ischemic heart disease in which half of the patients die outside hospital, the majority of them two hours after the first symptoms. Moreover, sudden death is the first symptom of coronary artery disease in 25% of cases. In this country few of these persons receive adequate basic life support (BLS) at the scene because a coordinated plan to teach BLS to the citizen does not yet exist in Switzerland. With the aid of specialized medical societies, the Swiss Red Cross and affiliated organizations, it is proposed to elaborate a plan to teach BLS to the general public in Switzerland on the basis of the future European guidelines for BLS. PMID- 2237343 TI - [Catheter ablation in ventricular tachycardia]. PMID- 2237344 TI - [Surgery of tachycardia]. PMID- 2237345 TI - [The treatment of persistent ventricular arrhythmias using implantable automatic defibrillators]. PMID- 2237346 TI - [Coronary angiography, percutaneous transluminal coronary angioplasty and coronary surgery, valvular interventions and anti-arrhythmia agents and fibrinolysis for acute myocardial infarction in Switzerland]. AB - Besides the description of the activities of the Working Group PTCA and Fibrinolysis of the Swiss Society of Cardiology, number and distribution of coronary angiograms and angioplasties (PTCA) and aortocoronary bypass operations performed in 13 Swiss centers during 1989 are presented and commented. It is of note that the number of PTCA procedures has increased further during the last year, whereas the number of bypass operations stayed fairly constant over the last three years. PTCA is done today almost as frequently as coronary artery bypass surgery in Switzerland. There are, however, marked differences between individual centers: the number of PTCA procedures in relation to coronary angiograms varies between 5% and over 40%. A large part of these interventions is performed at private hospitals. More than 85% of the PTCA procedures were single vessel procedures. Catheter interventions on heart valves and on the conductive system were done almost exclusively at University Hospitals. The 1989 survey of the treatment of acute myocardial infarction with fibrinolysis covers only hospitals with catheterization laboratories and is therefore not entirely representative for the total activity in Switzerland. Almost 20% (0-80%) of all patients admitted for acute myocardial infarction received fibrinolysis with important differences between individual centers. PMID- 2237347 TI - [The current status of cardiac rehabilitation in Switzerland]. AB - The aim of this study was to investigate the present situation of institutionalized cardiac rehabilitation in Switzerland. In 1989, there were 21 rehabilitation clinics and 21 ambulatory cardiac rehabilitation programs in Switzerland. All programs include physical activity and risk factor intervention. There is a wide variety of program selection and intensity. The medical care, the physical activity program, the strategy for risk factor intervention, the technical equipment and the emergency concept can be regarded as good in most rehabilitation clinics and in the ambulatory rehabilitation programs. However, a search for quality criteria for further activities in cardiac rehabilitation in Switzerland seems desirable. PMID- 2237348 TI - [Science and practice]. PMID- 2237349 TI - [Are additional filters made of niobium superior to the copper filter in dental radiology?]. AB - At a dental X-ray unit the effect of an additional filter made of niobium has been tested in the molar region of the mandible with respect to dose reduction. It has been compared against the effect of an additional filter made of copper. With regard to the same dose at the film, radiation dose at the surface of the patient proved to be slightly more reduced after application of the copper filter than after application of the niobium filter. Radiographs have been made by exposure of intraoral dental films (Kodak film Ultra Speed D) together with a hydroxyapatite step-wedge. Measurements of optical density resulted in the same values after application of the copper filter and the niobium filter, respectively. Reduced image contrast due to application of one of these additional filters proved to be helpful. In short, an additional copper filter placed in the X-ray beam shows identical or better results when compared against an additional filter made of niobium. PMID- 2237350 TI - [An in-vitro test procedure for evaluating dental restoration systems. 2. Toothbrush/toothpaste abrasion and chemical degradation]. AB - The development of an in-vitro test for evaluation of dental restorative systems comprised primarily the construction of a chewing simulator, which was able to produce occlusal mechanical load and thermal cycling. This machine was described in a previous publication. Additionally, chemical disintegration and toothbrush/toothpaste abrasion have to be included in the cycle. The aim of the present study was to develop appropriate test methods to simulate the two letter parameters and to integrate these methods in the in-vitro test cycle. The results indicated, that the toothbrush/toothpaste abrasion did not show any significant effect in the occlusal contact area. Chemical cycling induced a generalized swelling of the composite samples and a modified wear curve. The toothbrush/toothpaste abrasion led to a rough composite surface in the contact free area. PMID- 2237352 TI - [Traumatology in the deciduous dentition (I). The clinical and therapeutic aspects]. PMID- 2237351 TI - [Complications in overfilling of the root canals]. PMID- 2237354 TI - [The CPS, organ of the SSO, specializing in the area of health policy. Interview by Kurt Venner.. Societe Suisse d'Odonto-Stomatologie]. PMID- 2237353 TI - [Periodontal prosthodontics (I)]. PMID- 2237355 TI - [HIV infection and AIDS--the problems of labor law]. PMID- 2237356 TI - [Swiss dental medicine and the European dimension]. PMID- 2237357 TI - [Feminization in dental medicine]. PMID- 2237359 TI - [Reconstructions with bone-integrated implants. Interview by Kurt Venner]. PMID- 2237358 TI - [The ivory tower mentality belongs to the past. Interview by Kurt Venner]. PMID- 2237361 TI - [Learning from mistakes]. PMID- 2237360 TI - ["It smells like a dentist". The patient office survey by Dr. Jakob Rothlisberger, Langnau]. PMID- 2237362 TI - [Hyperpigmentation of the oral mucosa in HIV infection]. AB - In ten HIV-infected patients oral hyperpigmentations (HP) were observed, which seemed to be unrelated to any of the known endogenous or exogenous etiological factors. Light microscopy revealed accumulation of Fe-negative pigment in keratinocytes of the stratum basale as well as extra- and intracellularly within the subepithelial connective tissue. The ultrastructure of HP was characterised by the occurrence of melanosomes and premelanosomes within keratinocytes, melanocytes, macrophages and occasionally in fibroblasts, while especially in keratinocytes of the superficial cell layers immature melanosomes were found. Immunohistochemical examination pointed to an increase of HLA-DR positive cells and an altered distribution pattern of immunocompetent cells within the hyperpigmented mucosa. The finding of oral HP in HIV-infected patients may occur due to an increased activity of melanocytes, an increased production of melanosomes and their increased transfer to keratinocytes. PMID- 2237363 TI - [The shearing strength with the silicoater procedure of conditioned bonded retaining elements]. AB - The shear-bond strength of 120 sandblasted and silicoated metal elements (Wiron 88, Ni-Cr alloy) bonded with three different composites (ABC-cement, Superbond, Comspan opaque) to the plane of the prepared enamel surface of extracted teeth was measured. The effect of the interval between silicoating and bonding and that of 30 days' water storage was evaluated. The silicoating technique resulted in significantly higher bond strength than pure sandblasting, regardless of the composites used. After a one-day water storage the lowest bond strength was obtained with ABC-Cement and the highest with Superbond and Comspan opaque, independent of the interval between silicoating and bonding. After 30 days water storage elements bonded 30 min or 4 to 5 h after the silicoating procedure showed a loss of bond strength of an average of 25% regardless of the composites used. This decrease could not be measured with silicoated metal elements which were preserved by application of a bonding agent and bonded 24 h later. PMID- 2237364 TI - [The distribution of different collagen types and laminin in the gingiva of the common marmoset (Callithrix jacchus)]. AB - The distribution of the collagen types I, III, IV, V, VI and of the glycoprotein laminin have been examined in the healthy gingiva of the marmoset with the indirect immunofluorescence method. It has been shown that collagen type I formed thick fibrils in a wave-like pattern, while collagen type III formed thinner fibrils, especially under the epithelial basal membrane. Collagen type IV and laminin showed a strong fluorescence in the basal membrane (epithelium, vessels, nerves). Collagen type V has been demonstrated as a fine fibrillar pattern in the lamina propria and occasionally close to the basal membrane. Collagen type VI has been represented as a microfibrillar network in the connective tissue matrix with a brilliant pericellular fluorescence around vessels and nerves. The study showed the structural model of the connective tissue matrix of the marmoset gingiva and allows a later comparison between inflamed and healthy gingiva. PMID- 2237365 TI - [Learning from mistakes. A contribution to the grinding of abutment teeth for partial removable dentures]. PMID- 2237366 TI - [Reconstruction after a hemimaxillectomy. The functional restoration of the maxilla after a hemimaxillectomy]. PMID- 2237368 TI - [Until now no AIDS transmission in medical personnel]. PMID- 2237367 TI - [In search of a typical Swiss compromise. Interview by Kurt Venner]. PMID- 2237369 TI - On again, off again. Custom drug-delivery systems emulate the body's own patterns. PMID- 2237370 TI - New order. Artificial evolution creates proteins nature missed. PMID- 2237371 TI - Seeing the light. A glimmer of hope for retinal transplants. PMID- 2237372 TI - Adjusted agenda. AIDS activists accelerate alternative approaches. PMID- 2237373 TI - Cannabis comprehended. The "assassin of youth" points to a new pharmacology. PMID- 2237374 TI - Profile: vive la difference. Doreen Kimura plumbs male and female brains. PMID- 2237375 TI - [Terminology of ultrasonic vascular diagnosis]. AB - There is at present no accepted nomenclature regarding diagnostic vascular ultrasound. At two scientific meetings, the Study Group for Vascular Diagnosis of the German Society of Ultrasound in Medicine (DEGUM) developed a terminology for Doppler and duplex sonography of the arteries and veins supplying the brain and of peripheral vessels. The most important of these sonographic terms and their synonyms are presented. Recommendations as to which of the presently employed terms should be avoided, are given. PMID- 2237376 TI - [Spectrum analysis of Doppler signals]. AB - Doppler signal spectrum analysis contains useful haemodynamic information. Several parameters of the spectrum can be documented in numerics. Random interaction of the reflectors, the size of the ultrasound sample volume and the procedure of signal analysis influence the results and hence may cause misinterpretation of the data selected. Essential mechanisms influencing the clinician's Doppler-spectrum-analysis are discussed on the basis of a series of 59 angiographically and sonographically examined carotid arteries as well as in the light of theoretical considerations and a review of the literature. Peak frequency linked with a battery of spectrum parameters accuracy are useful to differentiate various degrees of lumen narrowing. Identification or exclusion of minor plaques cannot be achieved with sufficient sensitivity and specificity. PMID- 2237377 TI - [Color-coded Doppler sonography--possibilities for application in the neck area, the abdomen and the extremities]. AB - Colour coded Duplex sonography has definite advantages over duplex sonography for the investigation of neck and limb vessels. Diagnosis of arterial stenoses, occlusions and aneurysms can be readily made. The method also allows to follow the evolution after vascular surgery and percutaneous transluminal angioplasty. Deep venous thromboses can be reliably detected without the use of contrast media. Application for abdominal vascular diagnosis is still limited. PMID- 2237378 TI - [The value of obstetrical continuous-wave Doppler sonography: effect of various study modifications on the diagnosis of fetal growth retardation]. AB - In a comparative study on 484 pregnant women the influence of different modifications of the examination by continuous wave (cw)--Doppler was tested. The aim was to improve the detection rate of foetal growth retardation (IUGR): 1. Among different definitions of normal ranges the mathematical "smoothing" of normal values by regression analysis improves the results. 2. Of the most commonly used flow indices the A/B ratio is more reliable than the resistance and the pulsatility index. 3. Comparing the results of one to three examinations of the same patient in the course of pregnancy the relation of sensitivity to specificity is best after two examinations. 4. On evaluating the examinations of the umbilical arteries and the arcuate arteries, an intolerably false positive rate was found in the evaluation of arcuate arteries by cw Doppler. PMID- 2237379 TI - [Are Doppler methods appropriate for the study of adaptive maternal central circulation regulation in pregnancy?]. AB - Echocardiographic Doppler measurements of blood flow velocity are a noninvasive way of studying maternal central haemodynamics. Part 1 reports on conditions as well as on practical and theoretical problems recognized as contributing significantly to the use and interpretation of Doppler ultrasound techniques in the assessment of adaptive central circulatory regulation in pregnancy. The significance of different techniques is shown by assessments of the peak velocity and the velocity time integral. PMID- 2237381 TI - [Sonographic localization of ureteral calculi on extracorporeal shock wave lithotripsy]. AB - Using the new Dornier lithotriptor MPL 9000* (multi-purpose lithotriptor) 381 treatments of urinary stones were performed from July 1988 to December 1989, 107 (28%) of them for ureteral calculi. Sonography enables stone localisation even in many cases where positioning by conventional x-ray fluoroscopy would not be possible. In 20 cases of upper ureteral stones, localization had to be performed partly by indirect measures, i.e. at the end of the dilated ureter. In 10 ureteral stones of the middle third sonographic positioning and complete disintegration was achieved. Treatment was without anaesthesia and was performed in a comfortable supine position. Therapy of 77 ureteral calculi in the caudal part--without anaesthesia--has proved extremely successful. Since it is less invasive than other measures (e.g. uretero-renoscopy or loop extraction), it is now the method of choice for the treatment of stones in the middle and lower third of the ureter. PMID- 2237380 TI - [Sonographic diagnosis of Hill-Sachs lesions in unstable shoulder joints]. AB - In a prospective study we evaluated the use of diagnostic ultrasound for Hill Sachs lesions in unstable shoulder joints of 71 patients. The arthroscopic control of the sonographic findings showed a high sensitivity of 100%, a specificity of 89%, an accuracy of 95%, a positive predictive value of 93%, and a negative predictive value of 100%. With these results ultrasound seems to be more reliable than x-ray in the diagnosis of Hill-Sachs lesions. PMID- 2237382 TI - [Ultrasonic diagnosis prior to vitrectomy. Critical evaluation of 51 cases]. AB - In ophthalmology it is of increasing importance to assess intraocular pathology prior to vitroretinal surgery by means of B- and A-mode ultrasound. Even for the experienced examiner with advanced instrumentation, major problems can arise as to whether retinal detachment has developed or not. This task involves the ability for acoustical differentiation of thin tissue membranes. The authors compared preoperative ultrasonic results obtained in 51 cases with the surgical findings during vitrectomy. The presence or absence of retinal detachment was evaluated correctly in 33 cases (91.7%) using high resolution contact B-mode alone. In difficult cases maximal echo amplitudes reflected from the suspected membranes were evaluated using a hand-held A-mode transducer (level difference A mode echography) in addition to contact B-mode. Even the combined technique, though helpful in most cases, could not detect the presence or absence of retinal detachment in all cases. PMID- 2237383 TI - Maine school nurse works with Sister Teresa. PMID- 2237384 TI - Mortality and increasing drug use in Edinburgh: implications for HIV epidemic. AB - Mortality among a group of known drug users shows small numbers of deaths from AIDS so far but increasing deaths from overdose, especially in young women. Steadily rising numbers of drug injectors are observed. The need for a distinctly different educational approach in areas of very high seroprevalence is discussed and the requirement for close co-operation between prescribing sources identified. PMID- 2237385 TI - Cardiac arrhythmias associated with upper gastrointestinal endoscopy in elderly subjects. AB - Continuous Holter monitoring was performed before, during and after upper gastrointestinal endoscopy in 50 unselected, consecutive elderly patients (median age 80 years: range 68-89). In contrast to other studies the patients received no atropine or opiate premedication and were monitored for a prolonged period usually 24 hours after endoscopy. Comparison of a control period when the patient was lying at rest before endoscopy with the period of endoscopy itself revealed an increased frequency of arrhythmias during endoscopy. Forty-eight per cent of patients developed a new arrhythmia or an increased frequency of existing arrhythmia during endoscopy. All arrhythmias were short and self-terminating. Evidence of cardiac disease conferred a significantly increased risk of developing an arrhythmia during endoscopy. PMID- 2237386 TI - Contact lens related problems presenting in casualty. AB - The use of contact lenses in preference to spectacles has gained much popularity over recent years. This, however, is not without its complications and eye departments are now seeing an increasing number of contact lens related eye disease. This study seeks to show the range of complications seen, their treatment and outcome. It also outlines the types of contact lens in popular use, the reason for wear, the duration of wear and the sex, age and professional distribution of contact lens wearers. PMID- 2237387 TI - Paracetamol overdose in children. AB - The severity of paracetamol poisoning varies but in general, children are considered less susceptible to its toxic effects compared to adults. In this report we describe the relatively benign ingestion of paracetamol in children and also highlight a case of intrauterine exposure to a potentially toxic dose of paracetamol. PMID- 2237388 TI - A Scottish Hebridean antithrombin III deficient family--twelve years on. AB - The members of this family with ATIII deficiency have been followed for at least 12 years (1976-1989). All those with previous venous thrombo-embolism have been free from recurrence when on warfarin. During the half century 1931-1981, all 11 full term pregnancies in four affected patients were associated with venous thromboembolism; one patient was enigmatic having one full term pregnancy, without thrombotic event; between 1982 and 1989 three pregnancies have been actively managed with no clinical thrombosis. Management involved use of monitored, self administered, subcutaneous heparin before or very soon after conception and throughout pregnancy (warfarin having been stopped), planned delivery under cover of intravenous antithrombin III, reduction of heparin dosage at delivery and reintroduction of warfarin in the puerperium. The recognised hazards of heparin therapy in pregnancy did not occur. The involvement of the arterial system is reviewed. Clinical evidence provides tentative suggestions on (a) possible additional risk of cigarette smoking (b) avoidance of venography (c) avoidance of varicose vein surgery. A probe is now available for the defective antithrombin III gene in this family, but there has been no occasion yet to apply this in antenatal diagnosis. PMID- 2237389 TI - Clinical and biochemical pregnancy in two respective recipients without ovarian function following gamete intrafallopian transfers using oocytes from a single donor. AB - Infertility resulting from premature ovarian failure in two independent patients was treated using a combination of steroid replacement, oocyte donation and gamete intrafallopian transfer (GIFT). Following ovarian stimulation four oocytes were retrieved from a volunteer donor undergoing simultaneous laparoscopic sterilisation. Two oocytes were subsequently replaced into each recipient's fallopian tube together with capacitated sperm from their respective husbands. In one recipient (Turner's syndrome) an intrauterine sac with fetal heart present was observed by ultrasound six weeks post GIFT whereas in the second recipient (premature menopause) plasma beta-hCG reached a peak value of 954mIU/ml eighteen days after GIFT before decreasing rapidly in the absence of ultrasound evidence of pregnancy. Intramuscular administration of progesterone appeared to be necessary during the post-GIFT period for maintenance of pregnancy. The above treatment was carried out on a predominantly out-patient basis in a small assisted conception unit based in a teaching hospital. PMID- 2237390 TI - Primary retroperitoneal choriocarcinoma with pulmonary metastases in an elderly man. AB - We describe a 56-year old male smoker who presented with bilateral gynaecomastia and a large shadow in the upper zone of the right lung. Lobectomy revealed a haemorrhagic tumour at the apex of the right upper lobe. Histology revealed pure choriocarcinoma. Further investigations revealed normal testes and a retroperitoneal mass. Apart from histology, the other poor prognostic factors in this patient were the extragonadal site, gynaecomastia and age. Complete remission was achieved with an aggressive 5-day chemotherapy regime. Primary retroperitoneal choriocarcinoma is extremely rare and is predominantly seen in the age group between 20-30 years. PMID- 2237391 TI - Wilson's disease presenting as acute fulminant hepatic failure. AB - A fatal case of fulminant hepatic failure in an adolescent is described. Post mortem examination revealed the cause to be Wilson's Disease. This rare presentation is characterised by apparently atypical changes in copper metabolism. Wilson's Disease should be a differential diagnosis of any adolescent presenting in liver failure. PMID- 2237392 TI - A short history of medical degrees in the University of Aberdeen. AB - Aberdeen University was the first university in Great Britain to recognise the teaching of medicine by the creation of a teaching post, that of "mediciner." It was first occupied by James Cumyne, the burgh medical officer. The first medical degree granted by the university was doctus in medicina--learned in medicine. The degree was first awarded in 1630. The first examination paper for the M.D. was set in 1787 at the time of proposal to unit King's and Marischal Colleges and following criticism of the sale of degrees in medicine and midwifery "for ready money." The present degrees of M.B., ChB. were introduced in 1895. PMID- 2237393 TI - Rheumatology--the way ahead. PMID- 2237394 TI - Statewide breast cancer study. South Dakota Tumor Registrars' Association. AB - The South Dakota Tumor Registrars' Association reviewed breast cancer cases in South Dakota for the years 1983 and 1988. There were 225 cases in the 1983 group and 266 cases in the 1988 group. Data from this project revealed over 16% of patients in both groups had positive family histories for breast cancer. More cases in 1988 (119) were Stage I as compared to 1983 (69) suggesting earlier detection through increased awareness of the dangers of this disease by improved educational programs from 1983 to 1988, and the increased use of mammography in 1988 (86.8% of patients) as compared to 1983 (48% of patients). Modified radical mastectomy was the initial therapy in the majority of cases in both groups. Segmental resection followed by radiation therapy was the initial local therapy for 13 patients in 1988 as compared to six patients in 1983. Hormone receptor analysis was obtained in over 70% of patients in both groups. Adjuvant drug therapy was given to 25% of patients in both groups. Only two patients in 1983 and one patient in 1988 were entered on national research protocols. PMID- 2237395 TI - Accumulation of heavy metals in a lake ecosystem. AB - The concentrations of Cu, Zn, Fe, Mn, Ni, Cd, Pb and Co have been determined in water, bottom sediments, plankton, zoobenthos and ichthyofauna of mesotropic Lake Piaseczno located in eastern Poland. In water, sediments, plankton and benthos the most abundant heavy metals were Fe, Zn and Mn, whereas in fish Zn, Cu, and Mn were most abundant. The amount of heavy metals in the biotic components was dependent upon their concentration in water and partly upon the concentration in bottom sediments. A considerably less important role in the translocation of heavy metals is probably played by trophic interactions. PMID- 2237396 TI - Lead and cadmium contamination of soil and vegetables in the Upper Silesia region of Poland. AB - Studies of the lead and cadmium content of soils and vegetables from 126 allotments in 12 towns in a polluted region of Poland are described. Metal concentrations in parsley, celery, carrots and red beet were determined using AAS. In most cases, metal concentrations in soils and vegetables exceeded accepted standards and concentrations found in rural regions. A total of 756 vegetable samples were studied and only 170 met the standard for lead and 17 for cadmium. The lowest lead content was found in parsley roots and the highest in celery leaves. Cadmium content between species did not differ greatly and the highest concentrations were recorded for celery. The metal intake by the consumer was also calculated using questionnaire data concerning vegetable consumption. In relation to the reference area, the metal intake in the polluted area was 2-5 times higher for lead and 2-16 times higher for cadmium. The main species responsible for the high metal concentrations were carrots and red beet. Replacing carrots and red beet with the same species grown in an unpolluted region would reduce the consumer's metal intake from vegetables considerably. PMID- 2237397 TI - Absence of cadmium in the blood of horses fed oats grown on municipal sludge amended soil. AB - Effluents from a number of industries which are typically treated in municipal sewage plants result in cadmium-containing sludge. Disposal of such sewage sludge by application to agricultural land can result in uptake of cadmium by crops. In this study, oats were grown on soils which had been amended with sewage sludge from Syracuse, New York. The cadmium concentration in the sludge-grown oats was 1.79 ppm dry weight. Horses were fed the sludge-grown oats for 6 weeks during which time blood samples were taken for the determination of cadmium. No significant differences (p greater than 0.05) were found in the concentration of cadmium in the blood of the horses consuming the oats compared with that in the blood before feeding began (control). The well-known efficient accumulation of renal cadmium by horses may account for a lack of significantly increased cadmium in blood during the feeding period. PMID- 2237398 TI - Risk-based oversight of experiments in the environment. PMID- 2237399 TI - Filovirus infection in newly imported monkeys. PMID- 2237400 TI - Cold Spring Harbor turns 100. PMID- 2237401 TI - Gallo reports mystery break-in. PMID- 2237402 TI - Not enough monkey business. PMID- 2237403 TI - DNA looping and unlooping by AraC protein. AB - Expression of the L-arabinose BAD operon in Escherichia coli is regulated by AraC protein which acts both positively in the presence of arabinose to induce transcription and negatively in the absence of arabinose to repress transcription. The repression of the araBAD promoter is mediated by DNA looping between AraC protein bound at two sites near the promoter separated by 210 base pairs, araI and araO2. In vivo and in vitro experiments presented here show that an AraC dimer, with binding to half of araI and to araO2, maintains the repressed state of the operon. The addition of arabinose, which induces the operon, breaks the loop, and shifts the interactions from the distal araO2 site to the previously unoccupied half of the araI site. The conversion between the two states does not require additional binding of AraC protein and appears to be driven largely by properties of the protein rather than being specified by the slightly different DNA sequences of the binding sites. Slight reorientation of the subunits of AraC could specify looping or unlooping by the protein. Such a mechanism could account for regulation of DNA looping in other systems. PMID- 2237404 TI - Tetraplex formation of a guanine-containing nonameric DNA fragment. AB - A combination of spectroscopic and calorimetric techniques has been used to characterize the structures formed by a family of short, guanine-containing DNA single strands of the form d[GGTTXTTGG], X = A, C, G, T. In 1 molar NaCl at low temperatures, these molecules do not behave like single strands, but rather exhibit properties consistent with tetraplex formation. The standard state enthalpies, entropies, and free energies for formation of each tetraplex have been measured, as have preliminary nuclear magnetic resonance (NMR) spectra. In 1 molar KCl, the melting behavior of the structure or structures is more complex than in 1 molar NaCl. This observation may be related to the recently proposed "sodium-potassium switch." PMID- 2237405 TI - Underexpression of beta cell high Km glucose transporters in noninsulin-dependent diabetes. AB - The role of defective glucose transport in the pathogenesis of noninsulin dependent diabetes (NIDDM) was examined in Zucker diabetic fatty rats, a model of NIDDM. As in human NIDDM, insulin secretion was unresponsive to 20 mM glucose. Uptake of 3-O-methylglucose by islet cells was less than 19% of controls. The beta cell glucose transporter (GLUT-2) immunoreactivity and amount of GLUT-2 messenger RNA were profoundly reduced. Whenever fewer than 60% of beta cells were GLUT-2-positive, the response to glucose was absent and hyperglycemia exceeded 11 mM plasma glucose. We conclude that in NIDDM underexpression of GLUT-2 messenger RNA lowers high Km glucose transport in beta cells, and thereby impairs glucose stimulated insulin secretion and prevents correction of hyperglycemia. PMID- 2237406 TI - Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length. AB - The yeast protein RAP1, initially described as a transcriptional regulator, binds in vitro to sequences found in a number of seemingly unrelated genomic loci. These include the silencers at the transcriptionally repressed mating-type genes, the promoters of many genes important for cell growth, and the poly[(cytosine)1-3 adenine] [poly(C1-3A)] repeats of telomeres. Because RAP1 binds in vitro to the poly(C1-3A) repeats of telomeres, it has been suggested that RAP1 may be involved in telomere function in vivo. In order to test this hypothesis, the telomere tract lengths of yeast strains that contained conditionally lethal (ts) rap1 mutations were analyzed. Several rap1ts alleles reduced telomere length in a temperature-dependent manner. In addition, plasmids that contain small, synthetic telomeres with intact or mutant RAP1 binding sites were tested for their ability to function as substrates for poly(C1-3A) addition in vivo. Mutations in the RAP1 binding sites reduced the efficiency of the addition reaction. PMID- 2237407 TI - Protection of mice against the Lyme disease agent by immunizing with recombinant OspA. AB - Lyme borreliosis is a tick-borne illness caused by Borrelia burgdorferi. The gene for outer surface protein A (OspA) from B. burgdorferi strain N40 was cloned into an expression vector and expressed in Escherichia coli. C3H/HeJ mice actively immunized with live transformed E. coli or purified recombinant OspA protein produced antibodies to OspA and were protected from challenge with several strains of B. burgdorferi. Recombinant OspA is a candidate for a vaccine for Lyme borreliosis. PMID- 2237409 TI - Key primate research institute flounders. PMID- 2237410 TI - Final verdict on science budget: not bad at all. PMID- 2237408 TI - Detection of bcr-abl fusion in chronic myelogeneous leukemia by in situ hybridization. AB - Chronic myelogeneous leukemia (CML) is genetically characterized by fusion of the bcr and abl genes on chromosomes 22 and 9, respectively. In most cases, the fusion involves a reciprocal translocation t(9;22)(q34;q11), which produces the cytogenetically distinctive Philadelphia chromosome (Ph1). Fusion can be detected by Southern (DNA) analysis or by in vitro amplification of the messenger RNA from the fusion gene with polymerase chain reaction (PCR). These techniques are sensitive but cannot be applied to single cells. Two-color fluorescence in situ hybridization (FISH) was used with probes from portions of the bcr and abl genes to detect the bcr-abl fusion in individual blood and bone marrow cells from six patients. The fusion event was detected in all samples analyzed, of which three were cytogenetically Ph1-negative. One of the Ph1-negative samples was also PCR negative. This approach is fast and sensitive, and provides potential for determining the frequency of the abnormality in different cell lineages. PMID- 2237411 TI - Does medical mystery threaten biotech? PMID- 2237412 TI - A new bestiary for aging research. PMID- 2237413 TI - Gerontology research comes of age. PMID- 2237414 TI - In search of Methuselah: estimating the upper limits to human longevity. AB - Estimates of the upper limits to human longevity have important policy implications that directly affect forecasts of life expectancy, active life expectancy, population aging, and social and medical programs tied to the size and health status of the elderly population. In the past, investigators have based speculations about the upper limits of human longevity on observations of past trends in mortality. Here the estimate of the upper bound is based on hypothesized reductions in current mortality rates necessary to achieve a life expectancy at birth from 80 to 120 years and an expectation of life at age 50 from 30 to 70 years. With the use of conditional probabilities of death from complete life tables for the United States, reductions in mortality required to achieve extreme longevity (that is, 80 to 120 years) were compared with those resulting from hypothetical cures for all cardiovascular diseases, ischemic heart disease, diabetes, and cancer. Results indicate that in order for life expectancy at birth to increase from present levels to what has been referred to as the average biological limit to life (age 85), mortality rates from all causes of death would need to decline at all ages by 55%, and at ages 50 and over by 60%. Given that hypothetical cures for major degenerative diseases would reduce overall mortality by 75%, it seems highly unlikely that life expectancy at birth will exceed the age of 85. PMID- 2237415 TI - A thermodynamic scale for the helix-forming tendencies of the commonly occurring amino acids. AB - Amino acids have distinct conformational preferences that influence the stabilities of protein secondary and tertiary structures. The relative thermodynamic stabilities of each of the 20 commonly occurring amino acids in the alpha-helical versus random coil states have been determined through the design of a peptide that forms a noncovalent alpha-helical dimer, which is in equilibrium with a randomly coiled monomeric state. The alpha helices in the dimer contain a single solvent-exposed site that is surrounded by small, neutral amino acid side chains. Each of the commonly occurring amino acids was substituted into this guest site, and the resulting equilibrium constants for the monomer-dimer equilibrium were determined to provide a list of free energy difference (delta delta G degree) values. PMID- 2237416 TI - Side chain contributions to the stability of alpha-helical structure in peptides. AB - Short peptides that contain significant alpha-helical structure in aqueous solution allow the investigation of the role of amino acid side chains in stabilizing or destabilizing alpha-helix structure. A host-guest system of soluble synthetic peptides was designed that consisted of chains with the block sequence TyrSerGlu4Lys4X3Glu4Lys4, denoted EXK, in which X represents any "guest" amino acid residue. Circular dichroism spectroscopy indicates that the extent of helicity of these peptides follows the order Ala greater than Leu greater than Met greater than Gln greater than Ile greater than Val greater than Ser greater than Thr greater than Asn greater than Gly. This order differs from both host guest copolymer values (Met greater than Ile greater than Leu greater than Ala greater than Gln greater than Val greater than Thr greater than Asn greater than Ser greater than Gly) and the tendencies of these amino acids to occur in helices in globular proteins (Ala greater than Met greater than Leu greater than Gln greater than Ile greater than Val greater than Asn, Thr greater than Ser greater than Gly), but matches the order found in a series of synthetic coiled-coil alpha helices, except for Ser. Proton nuclear magnetic resonance analysis of several EXK peptides indicates that these peptides are partially helical, with the helical residues favoring the amino terminus. PMID- 2237418 TI - Inefficient remediation of ground-water pollution. PMID- 2237417 TI - Down-regulation of LFA-1 adhesion receptors by C-myc oncogene in human B lymphoblastoid cells. AB - The function of the c-myc gene and its role in tumorigenesis are poorly understood. In order to elucidate the role of c-myc oncogene activation in B cell malignancy, the phenotypic changes caused by the expression of c-myc oncogenes in human B lymphoblastoid cells immortalized by Epstein-Barr virus were analyzed. C myc oncogenes caused the down-regulation of lymphocyte function-associated antigen-1 (LFA-1) adhesion molecules (alpha L/beta 2 integrin) and loss of homotypic B cell adhesion in vitro. Down-regulation of LFA-1 occurred by (i) posttranscriptional modulation of LFA-1 alpha L-chain RNA soon after acute c-myc induction, and (ii) transcriptional modulation in cells that chronically express c-myc oncogenes. Analogous reductions in LFA-1 expression were detectable in Burkitt lymphoma cells carrying activated c-myc oncogenes. Since LFA-1 is involved in B cell adhesion to cytotoxic T cells, natural killer cells, and vascular endothelium, these results imply functions for c-myc in normal B cell development and lymphomagenesis. PMID- 2237419 TI - Drug abuse prevention programs. PMID- 2237420 TI - Animal carcinogen testing challenged. PMID- 2237421 TI - Stanford, claiming censorship, sues NIH. PMID- 2237422 TI - FDA gets Kessler; NIH gets left out. PMID- 2237423 TI - Immigration bill saves AIDS meeting. PMID- 2237424 TI - Animal rights activism threatens dissection. PMID- 2237425 TI - A meeting of the minds on the genome project? PMID- 2237426 TI - Miami vice metabolite. PMID- 2237427 TI - New HIV infection mechanism? PMID- 2237428 TI - The energetic basis of specificity in the Eco RI endonuclease--DNA interaction. AB - High sequence selectivity in DNA-protein interactions was analyzed by measuring discrimination by Eco RI endonuclease between the recognition site GAATTC and systematically altered DNA sites. Base analogue substitutions that preserve the sequence-dependent conformational motif of the GAATTC site permit deletion of single sites of protein-base contact at a cost of +1 to +2 kcal/mol. However, the introduction of any one incorrect natural base pair costs +6 to +13 kcal/mol in transition state interaction energy, the resultant of the following interdependent factors: deletion of one or two hydrogen bonds between the protein and a purine base; unfavourable steric apposition between a group on the protein and an incorrectly placed functional group on a base; disruption of a pyrimidine contact with the protein; loss of some crucial interactions between protein and DNA phosphates; and an increased energetic cost of attaining the required DNA conformation in the transition state complex. Eco RI endonuclease thus achieves stringent discrimination by both "direct readout" (protein-base contracts) and "indirect readout" (protein-phosphate contacts and DNA conformation) of the DNA sequence. PMID- 2237429 TI - Methylation of an immediate-early inducible gene as a mechanism for B cell tolerance induction. AB - Stage-specific gene regulation is important in determining cell function during development. Immature B cells expressing membrane-bound immunoglobulin M (mIgM) are sensitive to antigen-induced tolerance, whereas mature B cells are activated by antigen. Previous studies have established an association between Egr-1 gene induction and antigen receptor (mIgM)-mediated activation of mature B cells. Here it is shown that the immature B cell line WEHI-231 and tolerance-sensitive bone marrow-derived B cells do not express Egr-1. It is further shown that lack of inducible expression in these cells is due to specific methylation of the Egr-1 gene. Thus, covalent inactivation of an activation-associated gene may explain tolerance sensitivity at specific stages of B cell development. PMID- 2237430 TI - cdc2 gene expression at the G1 to S transition in human T lymphocytes. AB - The product of the cdc2 gene, designated p34cdc2, is a serine-threonine protein kinase that controls entry of eukaryotic cells into mitosis. Freshly isolated human T lymphocytes (G0 phase) were found to have very low amounts of p34cdc2 and cdc2 messenger RNA. Expression of cdc2 increased 18 to 24 hours after exposure of T cells to phytohemagglutinin, coincident with the G1 to S transition. Antisense oligodeoxynucleotides could reduce the increase in cdc2 expression and inhibited DNA synthesis, but had no effect on several early and mid-G1 events, including blastogenesis and expression of interleukin-2 receptors, transferrin receptors, c myb, and c-myc. Induction of cdc2 required prior induction of c-myb and c-myc. These results suggest that cdc2 induction is part of an orderly sequence of events that occurs at the G1 to S transition in T cells. PMID- 2237431 TI - Sequence-specific binding of human Ets-1 to the T cell receptor alpha gene enhancer. AB - Expression of the human T cell receptor (TCR) alpha gene is regulated by a T cell specific transcriptional enhancer that is located 4.5 kilobases (kb) 3' to the C alpha gene segment. The core enhancer contains two nuclear protein binding sites, T alpha 1 and T alpha 2, which are essential for full enhancer activity. T alpha 1 contains a consensus cyclic adenosine monophosphate (cAMP) response element (CRE) and binds a set of ubiquitously expressed CRE binding proteins. In contrast, the transcription factors that interact with the T alpha 2 site have not been defined. In this report, a lambda gt11 expression protocol was used to isolate a complementary DNA (cDNA) that programs the expression of a T alpha 2 binding protein. DNA sequence analysis demonstrated that this clone encodes the human ets-1 proto-oncogene. Lysogen extracts produced with this cDNA clone contained a beta-galactosidase-Ets-1 fusion protein that bound specifically to a synthetic T alpha 2 oligonucleotide. The Ets-1 binding site was localized to a 17 base pair (bp) region from the 3' end of T alpha 2. Mutation of five nucleotides within this sequence abolished both Ets-1 binding and the activity of the TCR alpha enhancer in T cells. These results demonstrate that Ets-1 binds in a sequence-specific fashion to the human TCR alpha enhancer and suggest that this developmentally regulated proto-oncogene functions in regulating TCR alpha gene expression. PMID- 2237432 TI - A map of visual space induced in primary auditory cortex. AB - Maps of sensory surfaces are a fundamental feature of sensory cortical areas of the brain. The relative roles of afferents and targets in forming neocortical maps in higher mammals can be examined in ferrets in which retinal inputs are directed into the auditory pathway. In these animals, the primary auditory cortex contains a systematic representation of the retina (and of visual space) rather than a representation of the cochlea (and of sound frequency). A representation of a two-dimensional sensory epithelium, the retina, in cortex that normally represents a one-dimensional epithelium, the cochlea, suggests that the same cortical area can support different types of maps. Topography in the visual map arises both from thalamocortical projections that are characteristic of the auditory pathway and from patterns of retinal activity that provide the input to the map. PMID- 2237433 TI - Analysis of junctional diversity during B lymphocyte development. AB - Immunoglobulin rearrangement is central to generating antibody diversity because of heterogeneity generated during recombination by deletion or addition of nucleotides at coding joints by the recombinase machinery. Examination of these junctional modifications revealed that the addition of nongermline-encoded nucleotides was more prevalent in adult versus fetal B cells, thus partially limiting the fetal antibody repertoire. In contrast, deletion of nucleotides occurs equivalently in B cells at different stages of development and at different points in B cell ontogeny. Finally, the bias in murine immunoglobulins for one DH segment reading frame occurs at the DHJH intermediate. PMID- 2237434 TI - Inhibition of the complement cascade by the major secretory protein of vaccinia virus. AB - The complement system contributes to host defenses against invasion by infectious agents. A 35-kilodalton protein, encoded by vaccinia virus and secreted from infected cells, has sequence similarities to members of a gene family that includes complement control proteins. Biochemical and genetic studies showed that the viral protein binds to derivatives of the fourth component of complement and inhibits the classical complement cascade, suggesting that it serves as a defense molecule to help the virus evade the consequences of complement activation. PMID- 2237435 TI - Does diphtheria toxin have nuclease activity? PMID- 2237436 TI - Experts clash over cancer data. PMID- 2237437 TI - Orphan drug compromise Bush-whacked. PMID- 2237438 TI - Technical advances power neuroscience. PMID- 2237439 TI - DOE to map expressed genes. PMID- 2237440 TI - Self-incompatibility: a self-recognition system in plants. AB - Self-incompatibility (SI), a genetically controlled mechanism to prevent inbreeding in plants, offers a relatively simple model system for studying the interactions between plant cells or between a plant cell and the secreted product or products of another cell. Examples of two major types of SI, gametophytic and sporophytic, have been studied by cloning cDNAs corresponding to glycoproteins of the female tissues that segregate with particular variants encoded by the putative S locus. These secreted glycoproteins are envisaged to interact with the currently undescribed pollen component to cause arrest of pollen tube growth. PMID- 2237441 TI - Localized all-or-none calcium liberation by inositol trisphosphate. AB - Laser confocal microscopy was used to monitor calcium ion (Ca2+) liberation from highly localized (micrometer) regions of intact Xenopus oocytes in response to photo-released inositol 1,4,5-trisphosphate (InsP3). Local Ca2+ release varied in an all-or-none manner with increasing amount of InsP3, in contrast to signals recorded from larger areas, which grew progressively as the concentration of InsP3 was raised above a threshold. Liberation of Ca2+ was restricted to within a few microns of the site of InsP3 release and, in response to agonist activation, localized regions of the oocyte showed asynchronous oscillations in cytoplasmic Ca2+ release. Results obtained with this technique provided direct evidence that InsP3-induced Ca2+ liberation was quantized and suggest that the InsP3-sensitive Ca2+ pool may be a collection of independent, localized compartments that release Ca2+ in an all-or-none manner. PMID- 2237442 TI - A cytoplasmic protein inhibits the GTPase activity of H-Ras in a phospholipid dependent manner. AB - A cytoplasmic protein has been identified that inhibits the guanosine triphosphatase (GTPase) activity of bacterially synthesized, cellular H-Ras protein. This GTPase inhibiting protein is able to counteract the activity of GTPase activating protein (GAP), which has been postulated to function as a negative regulator of Ras activity. The potential biological importance of the GTPase inhibiting protein is further supported by its interaction with lipids. Phospholipids produced in cells as a consequence of mitogenic stimulation increase the activity of the GTPase inhibiting protein, as well as inhibit the activity of GAP. The interaction of such lipids with each of these two regulatory proteins would, therefore, tend to increase the biological activity of Ras and stimulate cell proliferation. PMID- 2237443 TI - Mesodermal control of neural cell identity: floor plate induction by the notochord. AB - The floor plate is a specialized group of midline neuroepithelial cells that appears to regulate cell differentiation and axonal growth in the developing vertebrate nervous system. A floor plate-specific chemoattractant was used as a marker to examine the role of the notochord in avian floor plate development. Expression of this chemoattractant in lateral cells of the neural plate and neural tube was induced by an ectopic notochord, and midline neural tube cells did not express the chemoattractant after removal of the notochord early in development. These results provide evidence that a local signal from the notochord induces the functional properties of the floor plate. PMID- 2237444 TI - Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. AB - Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation. The functions of these proteins can be antagonized by several methods, each with specific limitations. Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappa B consensus sequences. The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-kappa B. The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner. Octamer-dependent activation of a reporter plasmid or NF-kappa B-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line. Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 (IL-2) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer. The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral, immunosuppressive, or other therapeutic effects. PMID- 2237445 TI - Changes in the fibrinolytic system during pregnancy. PMID- 2237446 TI - Evolutionary assembly of blood coagulation proteins. PMID- 2237447 TI - Pathologic fibrinolysis as a cause of clinical bleeding. PMID- 2237449 TI - Current and future radiopharmaceuticals for brain imaging with single photon emission computed tomography. AB - Development of radiopharmaceuticals for functional brain imaging has progressed rapidly in recent years. Measurement of regional cerebral blood flow in humans can be achieved by using [123I]-iodoamphetamine or [99mTc]-HMPAO. Several other lipid-soluble [99mTc]-technetium complexes are currently undergoing clinical trials. New 123I-labeled agents designed to measure central nervous system receptors, including D1 and D2 dopamine, serotonin, muscarinic, and benzodiazepine receptors, have been developed. In conjunction with single photon emission computed tomography, they may provide useful tools to evaluate brain function related to changes in receptor concentration. PMID- 2237448 TI - Instrumentation and computers for brain single photon emission computed tomography. AB - Cerebral single-photon emission computed tomography (SPECT) requires attention to the instrumentation because of the anatomical location of the head at one end of the body, with a generally narrower diameter than the rest of the body. For a number of years, there have been SPECT units designed especially for head work, as well as general-purpose units that have performed well in imaging the head. The current emphasis on cerebral perfusion, using either agents that wash in and out with blood flow or agents that reflect blood flow in their static distribution, has allowed a concentration on imaging hardware and computer hardware and software for this purpose. PMID- 2237450 TI - An overview of the contribution of regional cerebral blood flow studies in cerebrovascular disease: is there a role for single photon emission computed tomography? AB - Regional cerebral blood flow (rCBF) findings and their application to cerebrovascular disease are reviewed. Although the coupling of cerebral blood flow and metabolism are best studied with positron emission tomography, single photon emission computed tomography measurements of rCBF can contribute to patient management. Potential indications for the use of rCBF functional brain imaging include differential diagnosis, early prediction of late recovery in the late subacute and chronic phases of stroke (3 months or more postonset), and evaluation of vasospasm following subarachnoid hemorrhage. PMID- 2237451 TI - Single photon emission computed tomography in epilepsy. AB - Functional brain imaging by either single photon emission computed tomography (SPECT) or positron emission tomography (PET) is now a well-established technique in the diagnosis and evaluation of the epilepsies. Perhaps only in stroke have these emerging technologies proven of greater significance. Scalp, cortical, or depth electroencephalographic (EEG) data previously have been the gold standards for the localization and subcharacterization of epileptic activity in the human brain. Yet, they are fraught with difficult interpretations, technical difficulties, and limitations in sampling accuracy. Both SPECT and PET have localizing power approaching that of combined scalp and depth EEG. In the following discussion, a brief overview of the results of PET investigations in epilepsy is presented as background and comparative material for the concurrent and, more recently, dominant role of SPECT in evaluating patients with seizure activity. SPECT results in the interictal state in partial and generalized seizure activity are reviewed followed by an analysis of the role of ictal SPECT imaging in epilepsy. Next, relationships among interictal hypoperfusion (or hypometabolism) and computed tomography, magnetic resonance imaging, neuropathology, clinical severity, and cognitive function are discussed. The role of perfusion or metabolism imaging in the management of antiepileptic pharmacotherapy is also discussed, and the potential for receptor imaging in the evaluation of the epilepsies is examined. Finally, application in pediatric epilepsy are presented. PMID- 2237452 TI - Single photon tomography in Alzheimer's disease and the dementias. AB - Measurements of brain blood flow has evolved over the past 50 years, and during the latter half of that time radionuclide techniques have been used to study this important function. Using Xenon 133 and scintillation multiprobe systems, several teams of investigators measured regional cerebral blood flow (rCBF), and noted that under many circumstances it could be equated with local brain physiological activity. The dementias were investigated using the scintillation multiprobe method, and posterior flow deficits were described in patients who were thought to have Alzheimer's disease. The multiprobe technique gave way first to planar, and then tomographic imaging, with initial favorable results achieved by positron emission tomography (PET). Soon investigators learned to measure rCBF with single photon emission computed tomography (SPECT) using high-sensitivity systems and 133Xe as a tracer, or high-resolution systems with 123I-iodoamphetamine (IMP), and later, 99mTc-HMPAO. Three-dimensional tomographic imaging shows to advantage the flow patterns that characterize Alzheimer's disease, with rCBF reductions in temporal, parietal, and sometimes frontal areas, as opposed to randomly distributed deficits in multiinfarct dementia, reduced frontal flow in entities such as Pick's disease, and others. Herein we will review our own experience with high-sensitivity rCBF SPECT in 119 patients with dementia, and with high resolution SPECT, using a new, three-camera scanner and 99mTc-HMPAO in an additional 39 patients. SPECT rCBF study of patients with dementia and Alzheimer's disease, will aid in separating patients with untreatable Alzheimer's from those patients who may have treatable causes of dementia, and will be useful in evaluating experimental drugs for the treatment of Alzheimer's disease. PMID- 2237453 TI - Brain imaging in acquired immunodeficiency syndrome dementia complex. AB - Human immunodeficiency virus (HIV) infections are accompanied by many different types of neurological complications. Opportunistic infections and neoplasms, particularly lymphoma, are often an underlying cause for these complications in patients with acquired immunodeficiency syndrome (AIDS). Frequently, these can be detected by cerebrospinal fluid (CSF) examination, double-dose contrast transmission computed tomography (CT), and/or magnetic resonance imaging (MRI). It has become apparent that the HIV itself is responsible for a significant percentage of neurological disease in the HIV-seropositive individual. The onset may be subtle and may occur before the onset of frank immunosuppression. Diagnosis of HIV encephalitis or AIDS dementia complex (ADC) is complicated by the frequent coexistence of opportunistic infections. Structural neuroimaging (CT or MRI) shows atrophy and in some case white matter abnormalities, but imaging pathological correlation suggests that these modalities are relatively insensitive to the presence of HIV brain infection. Functional neuroimaging, both 18fluorodeoxyglucose positron emission tomography (PET) for evaluation of glucose metabolism and 123I iodoamphetamine or 99mTc-HMPAO single-photon emission computed tomography (SPECT) for evaluation of cerebral perfusion, can demonstrate abnormalities in the subcortical gray matter structures and the cerebral cortex in patients with ADC. These abnormalities may be observed early in the course of ADC even when MRI is negative and the patient is relatively asymptomatic. Also, PET and SPECT may be useful to follow progression of the dementia or response to therapy. PMID- 2237454 TI - Thyrotoxicosis with low thyroidal uptake of radioiodine. PMID- 2237455 TI - Enterogastric reflux demonstrated by radionuclide hepatobiliary scintigraphy. PMID- 2237456 TI - Sound and vibration in pregnancy, Part II. PMID- 2237457 TI - Physiological correlates of development of the human cochlea. PMID- 2237459 TI - Effects of early auditory experience on development of binaural pathways in the brain. PMID- 2237458 TI - Development of auditory coding in the central nervous system: implications for in utero hearing. PMID- 2237460 TI - Prenatal and perinatal risks of hearing loss. PMID- 2237461 TI - The fetal vibroacoustic stimulation test: an update. PMID- 2237462 TI - Vibration: principles, measurements, and health standards. PMID- 2237463 TI - Low frequency noise and vibration: role of government in occupational disease. PMID- 2237464 TI - Pregnant women in the workplace. PMID- 2237465 TI - Selected legal issues related to sound and vibration in pregnancy. PMID- 2237466 TI - The group B streptococci: from natural history to the specificity of antibodies. PMID- 2237467 TI - Antimicrobial defenses in the neonate. AB - Serious life-threatening neonatal infections with microbial species that are infrequently associated with infections in adults are related to the immature immune system of human newborn infants. The usually sterile intrauterine environment of the fetus is associated with a primed but inactive immune system at the time of birth. Sudden introduction into a complex microbial world stimulates the inflammatory system and an effective host defense rapidly develops. Defense mechanisms include innate phagocytic and complement systems, and specific adaptive immunity including antimicrobial antibodies. Fortunately, neonates have protective antibodies against many microbes at birth provided by their mothers via placental transfer of IgG. Specific antimicrobial antibody production by the newborn infant is delayed. Neutrophil numbers in the circulation are high in the normal neonate, but the bone marrow pool of cells is limited. Chemotactic responsiveness of circulating phagocytic cells is decreased in comparison with adult cells, although phagocytic and microbicidal activity of neonatal neutrophils and monocytes are normal. The newborn infant's lymphocyte system is relatively mature, and neonatal mononuclear cells have normal antigen presenting and secretory function. T lymphocytes are present in normal numbers and although response of these cells to antigens is somewhat slower than in adult cells, a near normal response suggests intrauterine stimulation by maternally derived immunoregulators. B lymphocytes are also present in newborn human infants. However, maturation of B lymphocytes into antibody-producing plasma cells occurs gradually during the first weeks of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237468 TI - Murine type-specific monoclonal antibodies in experimental group B streptococcal infection: interaction with complement components and phagocytes. PMID- 2237469 TI - Escherichia coli infection in neonates: humoral defense mechanisms. PMID- 2237470 TI - Neonatal listeriosis. PMID- 2237471 TI - Acute suppurative thyroiditis with progression to abscess. PMID- 2237472 TI - The role of ultrasound in the clinical practice of obstetrics. PMID- 2237473 TI - Update on the safety of ultrasound in obstetrics. PMID- 2237474 TI - Gestational age: what to measure and when. PMID- 2237475 TI - Fetal growth disturbances. AB - IUGR is a fetal disorder characterized by diminished fetal growth, especially in the third trimester. Growth retardation may be due to primary placental insufficiency or may result from a variety of maternal or fetal causes and is associated with elevated perinatal mortality and morbidity. Numerous conventional and Doppler ultrasound criteria have been proposed for diagnosing IUGR prenatally, but none on its own permits confident diagnosis of this condition. Diagnosis or exclusion of IUGR can best be achieved by the combined use of three parameters: estimated fetal weight, amniotic fluid volume, and maternal hypertension. When IUGR is suspected based on these parameters, Doppler ultrasound can help to determine the prognosis. Large fetuses, particularly those weighing more than 4,000 grams at birth, are at risk for perinatal morbidity and mortality due to obstetrical complications. These fetuses occur more frequently and are at especially high risk in diabetic mothers. The estimated fetal weight is the most direct parameter for diagnosing LGA and macrosomia and is moderately accurate with positive predictive values up to 67% in the general population and 77% in diabetics. It can be an important factor in deciding on the route of delivery in diabetic mothers. PMID- 2237476 TI - The fetal central nervous system. AB - CNS anomalies are some of the most common and clinically important congenital malformations encountered in utero. Improved detection of CNS anomalies requires a systematic survey of the cranium and spine as a part of all obstetric sonograms performed after the first trimester. Recognition of characteristic cranial findings associated with spina bifida can dramatically improve detection of small spinal defects before the time of fetal viability, even when the sonogram is performed for low-risk indications. Patients suspected to be carrying a fetus that has a cranial or spinal anomaly should ideally be referred to a tertiary center for confirmation of the defect, evaluation of possible additional anomalies, and for patient management and counseling. PMID- 2237477 TI - Disorders of the fetal thorax and abdomen. AB - Many disorders of the fetal thorax and abdomen can be evaluated using ultrasound. Even when a definitive diagnosis cannot be made prenatally, sonography can provide valuable clinical information regarding the nature and location of the abnormality, associated anomalies, and the presence of secondary complications. An awareness of these disorders and their sonographic appearance is important to impact upon obstetrical management and overall prognosis. PMID- 2237478 TI - Fetal genitourinary tract. PMID- 2237479 TI - Nonimmune hydrops fetalis: a heterogeneous disorder and therapeutic challenge. PMID- 2237480 TI - [To stop smoking: "yes", "no", "maybe". A course for freedom to be attempted]. PMID- 2237481 TI - [The World Tobacco-Free Day: 31 May. "A childhood and a youth without tobacco"]. PMID- 2237482 TI - [Children and youth, victims of tobacco]. PMID- 2237483 TI - [Women and tobacco]. PMID- 2237484 TI - [When and how to extubate in the recovery room]. PMID- 2237485 TI - [Reflections on theoretical models and their applicability]. PMID- 2237486 TI - [Filariasis]. PMID- 2237487 TI - [A simple cure for diarrhea]. PMID- 2237488 TI - [Encounter groups]. PMID- 2237489 TI - [How and when should one act against postoperative fever?]. PMID- 2237490 TI - [You have to resign yourself!. Interview by Ruth Landy]. PMID- 2237491 TI - [Resin replaces the traditional gypsums]. PMID- 2237492 TI - [The bone marrow transplant in childhood]. PMID- 2237493 TI - [Recommendations for the use of drugs in arterial hypertension. The Chief Medical Committee of Social Security]. PMID- 2237495 TI - [The responsibility of the Church in education for health]. PMID- 2237494 TI - [Education for health]. PMID- 2237496 TI - [The human person]. PMID- 2237497 TI - [Primary health care: the clinical, social and ethical aspects]. PMID- 2237499 TI - [Education for the family and health professionals]. PMID- 2237500 TI - [The sterilization of a female psychiatric patient. Towards an ethical evaluation]. PMID- 2237498 TI - [The prevention of cancer every week of the year]. PMID- 2237501 TI - [The concrete action of the Church in education for health. Organized intervention]. PMID- 2237502 TI - [The body and old age]. PMID- 2237503 TI - [Churches as an avenue for the control of arterial hypertension]. PMID- 2237504 TI - International migration of health manpower in Sub-Saharan Africa. AB - This paper concerns itself with a few questions related to the impact of the emigration of health manpower on the health status of individuals and economic development of Sub-Saharan Africa (SSA). The paper evaluates the harmfulness of the migration from Sub-Saharan Africa. The analysis leads to some observations about the effect of the quality of the migration on Africa's health care system development and the appropriateness of some of Africa's policies for controlling the migration. PMID- 2237505 TI - Medicine and the social sciences in Africa. PMID- 2237506 TI - Debt crisis, health and health services in Africa. AB - In the early 1960s when most of Africa became independent, the hope for the resolution of the related problems of poverty, illiteracy and disease became the primary agenda of its sovereign states. There were indeed initial gains in various aspects of social infrastructure, especially education and medical services. Beginning from the mid 1970s, but particularly since 1980, this initial progress is, however, being reversed as Africa totters under an excruciating debt burden and accompanying austerity programmes. This essay provides a kaleidoscope of this ominous decay with particular reference to health and health services. Several proposals for the way forward are discussed. PMID- 2237507 TI - Economic development strategies: maternal and child health. PMID- 2237508 TI - Health services for the aged in Sub-Saharan Africa. AB - This paper addresses itself to the problems faced by the aged with regards to the use and availability of health services in Sub-Saharan Africa (SSA). The paper maintained that the development of a sound public policy on ageing in SSA requires two types of knowledge; an understanding of what consequences will follow from a particular course of action, and an evaluation of the desirability of those consequences. It concluded that there is a need to improve the database that will form a basis for any policy prescription that is geared towards alleviating the problems of the aged in this sub-region. PMID- 2237509 TI - Malaria in Sub-Saharan Africa. AB - Malaria as a threat to health has remained undaunted in Sub-Saharan Africa (SSA). It has been mathematically modelled, vertically attacked and continuously appraised and yet it continues unabated. Malaria is an acute and chronic disease caused by intracellular protozoa of the genus Plasmodium which are transmitted by the bite of female Anopheles mosquitoes. Approximately 2.6 billion people are at risk worldwide resulting in at least 100 million clinical cases and of the order of 1 million fatalities. The social and economic consequences of such morbidity and mortality have not been adequately documented. PMID- 2237510 TI - Impact of HIV/AIDS on African children. AB - In Central and East Africa, pediatric human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) are becoming increasing threats to child health due to the predominance of heterosexual transmission of HIV, high HIV infection rates in women of reproductive age and high birth rates. This paper examines the potential impact of HIV/AIDS on orphanhood and under-five mortality in 10 Central and East African countries. The author estimates that, in the 10 countries studied, HIV/AIDS in children under age five will cause between one-quarter and half a million child deaths annually by the year 2000. Whereas the United Nations estimate (without AIDS) and target for the under-five mortality rate in this 10-country region by the year 2000 are 132 and 78, respectively, HIV/AIDS will cause the under-five mortality rate to rise to between 159 and 189. Increasing HIV/AIDS-related adult mortality is creating a large and growing number of children under age 15 whose mothers have died of HIV/AIDS. During the 1990s, HIV/AIDS will kill a total of between 1.5 and 2.9 million women of reproductive age in this region, producing between 3.1 and 5.5 million AIDS orphans--which means that between 6 and 11% of the population under age 15 will be orphaned. National and international government and nongovernment service providers in Central and East Africa need to recognize this potential impact of HIV/AIDS on children, expand AIDS-prevention efforts, and develop policies and programs to address children's HIV/AIDS-related needs. PMID- 2237511 TI - Orphans as a window on the AIDS epidemic in Sub-Saharan Africa: initial results and implications of a study in Uganda. AB - Provisional estimates from a Save the Children Fund enumeration study in four Ugandan districts indicate that the total number of orphans (one or both parents missing) ranges between 620,000 and 1,200,000. Needs assessments with guardians and local administrators show that although extended family networks are absorbing these children according to traditional rules, they may be vulnerable to increased mortality due to economic and health stresses on their caretakers, many of whom are elderly persons. The orphan burden will increase in Uganda and other Sub-Saharan African countries over the next few years. Allocation of additional national and international resources must be considered to avert breakdowns in community and familial support systems and consequent increases in under 5 mortality. The orphan burden is a window on the potential for massive social breakdown and dislocation in Sub-Saharan Africa resulting from high AIDS related mortality. Methodologies for data collection and planning that use indigenous political systems must be built quickly to avert disaster. PMID- 2237512 TI - Substance abuse, health and social welfare in Africa: an analysis of the Nigerian experience. AB - Substance abuse has become a significant problem in the African continent in recent years. Reports of increasing abuse of alcohol and cannabis have appeared in many countries. In Nigeria, beginning from the early 1980s, the abuse of cocaine and heroin has been added to the problem. Even though epidemiological findings show low rates of abuse of these illicit substances in the general population, hospital-based studies point to a growing incidence of cocaine and heroin-related mental health problems. Information from recent studies in Nigeria is utilized in an analysis of the drug abuse scene. It is suggested that drug trafficking by Nigerians, which has been unprecedented in the past 10 years, has contributed to the observed shift in the pattern of drug abuse from cannabis and alcohol to cocaine and heroin. It is suggested that there should be regional sharing of information on drug abuse in the continent and that governments should treat as urgent the formulation and implementation of broadly-based drug policies. PMID- 2237513 TI - Psychology and health in Africa. PMID- 2237514 TI - Aging as a feminist issue. PMID- 2237515 TI - My name is legion, for we are many: diagnostics and the psychiatric client. PMID- 2237516 TI - The impact of race on volunteer helping relationships among the elderly. AB - As programs solicit their help in providing transportation, shopping assistance, telephone reassurance, counseling, and information and referral to needy elderly people, older adults are going to fill increasingly important roles as volunteers in the social service system for this aging society. Little empirical work has been done on effective volunteer behavior. This article aims to increase understanding of this topic by exploring how race influences relationships between volunteers and the people they serve. This analysis reveals that race by itself does not affect volunteer helping behavior; black and white older adults perform similarly in volunteer roles on measures of time committed to service and satisfaction levels of clients. However, the racial composition of the dyad does have significant effects on the helping relationship; higher levels of contact and client satisfaction are reported when the volunteer and the client are of the same race. Professional training and support are necessary to overcome problems associated with racial differences between volunteers and their clients. PMID- 2237517 TI - Working families and eldercare: a national perspective in an aging America. AB - The competing demands of employment and caring for a dependent elderly family member can create stress for families, and some employers are becoming concerned about the impact of eldercare on the workplace. This first national survey of workers examined the extent of eldercare and its impact on workers. In this article, the authors profile the employees who described themselves as caregivers, the older people they were caring for, the care they were giving, the extent to which they reported conflict between their work and caregiving responsibilities, and the workplace supports they would have found helpful in managing these roles. Women were devoting more time to caregiving and were more likely to report work and caregiving conflict than were men. Social workers in occupational and community settings can play a key role in providing information about eldercare services, in counseling caregivers, and in advocating for employee benefits and community services to help workers maintain both work and family roles. PMID- 2237518 TI - Personnel to serve the aging in the field of social work: implications for educating professionals. AB - This survey of 476 members of the National Association of Social Workers (NASW) was conducted to better describe their characteristics, educational background, and perceptions of the field of aging. The findings indicated that although 26 percent (29,650) of NASW members currently work with older people, 62 percent of those who do not work with older people reported that gerontology knowledge was required in their current jobs. Respondents perceived that the area of aging would be much larger and more important in the future, and they recommended increased gerontological preparation for all social work students. PMID- 2237519 TI - The consequences of elderly wives caring for disabled husbands: implications for practice. AB - This study examines the mental well-being and special problems of 188 elderly wives identified as the primary caregivers who care for their disabled husbands. The findings indicate that the women have low morale scores associated with the arduous tasks of caregiving. Despite low morale scores, the health status of an elderly wife appeared to contribute significantly to her ability to cope with the caregiving responsibilities of a disabled spouse. Constant care and supervision, emotional and physical strain, and reduced social contact and finances were the major problems encountered in the caregiving commitment. PMID- 2237520 TI - Older women and poverty. AB - The popular perception of the financially secure economic status of elders, referred to as the "greening of the aged," does not reflect the reality faced by many older women. Older women's economic positions depend largely on marital status. Women who are widowed and other women living alone are among the most poor. Cuts in Social Security benefits, viewed by some policymakers as a possible solution to the problem of the federal budget deficit, would exacerbate the poverty of older women who rely on Social Security as their main source of income. Social workers concerned with poverty among older women must ensure that older women's interests are not sacrificed to resolve the federal deficit. PMID- 2237521 TI - Family response to the farm crisis: a study in coping. AB - The recent farm crisis created major economic disruptions for rural communities and families. To understand the effects of these disruptions on rural families, a study was conducted with community leaders and adult members of rural families that had experienced these disruptions. Family members experienced many stress reactions, especially withdrawal and depression. Families coped primarily by marshalling family efforts to solve financial problems and to provide emotional support. Significant barriers prevented people from turning to others in the extended family and the community for help. Family members created barriers by their withdrawal and their sense of individualism and shame. Judgmental attitudes and lack of understanding by others as well as demeaning and inappropriate criteria for help also created barriers. Interventions require monitoring policy issues and mobilizing community resources, as well as helping individual families to cope. PMID- 2237522 TI - A social work practice model of case management: the case management grid. AB - Case management is a major component of the current mainstream of social work practice. Nevertheless, the field has failed to adequately conceptualize case management. The first step in defining case management practice is to separate it from the administrative structure that forms the context of practice. The next step is to delineate the two basic dimensions of case management--enabling and facilitating. The role of the social work case manager is to integrate formal systems of care with the activities of families and primary groups. Case management practice focuses on enabling individuals and primary groups to reach their full potential and on facilitating more effective interaction with the larger social environment. The case management grid illustrates how social work practitioners integrate enabling and facilitating into their practice approaches. PMID- 2237523 TI - The empirical base for the implementation of social skills training with maltreated children. AB - Empirical research on the psychosocial sequelae of child maltreatment has identified numerous and severe social skills deficits in abused and neglected children that negatively affect their healthy adjustment. Social skills training programs have been successful in helping adults and nonmaltreated children improve their skills in interpersonal communication, problem solving, self control, assertiveness, and stress management. Such training appears promising for intervention with maltreated children. Guidelines and rationales are presented for developing social skills training programs specifically focused on the developmental and situational needs of abused and neglected children. PMID- 2237524 TI - Social work's contribution to psychosocial rehabilitation. AB - This article describes the social work profession's contribution to the emerging field of psychosocial rehabilitation and presents principles that enable social workers to work effectively with people with chronic mental illnesses. Although model psychosocial rehabilitation programs have been established throughout the United States, psychosocial rehabilitation has not been widely articulated in the social work literature. This article specifically defines the psychosocial rehabilitation approach in the model programs, often called "clubhouses," and describes the contribution of social work to the model's development. PMID- 2237525 TI - [Aspirin]. PMID- 2237526 TI - [The patient with aspiration drainage. Nursing care]. PMID- 2237527 TI - [AIDS and lymphoma. Some problems for the patient care team]. PMID- 2237528 TI - [Hematopoietic growth factors. Therapeutic trials]. PMID- 2237529 TI - [Interleukin 2 in oncology]. PMID- 2237530 TI - [GM-CSF. Cellular growth factor]. PMID- 2237531 TI - [Gene therapy in onco-hematology. Perspectives and ethics]. PMID- 2237532 TI - [Trans-retinoic acid. Treatment by differentiation of acute promyelocytic leukemia]. PMID- 2237533 TI - [Central catheter sepsis. Diagnosis and current treatments]. PMID- 2237534 TI - [Intrathecal injection of morphine. Nursing interventions]. PMID- 2237535 TI - [Allogenic bone marrow transplant. Latest developments]. PMID- 2237536 TI - [Hematologic reconstitution after transplant with umbilical cord blood cells]. PMID- 2237537 TI - [Allogenic bone marrow transplants in voluntary unrelated donors]. PMID- 2237538 TI - [3rd International Congress on Wound Care]. PMID- 2237539 TI - [Reduction in the use of allogenic blood products]. PMID- 2237540 TI - [Intra-arterial treatment of breast cancers]. PMID- 2237541 TI - [Indications and techniques for intraperitoneal catheters]. PMID- 2237542 TI - [Injectable anti-cancer drugs. Stocking, preparation and administration]. PMID- 2237543 TI - [Implantable vascular access ports. Use and maintenance]. PMID- 2237544 TI - [Onco-hematology service. The suffering of the nurses]. PMID- 2237545 TI - [Nurses and death in the hospital. Duties and role]. PMID- 2237546 TI - [AIDS. Some facts]. PMID- 2237547 TI - A late look at the fourth: freedom botched and blotched. PMID- 2237548 TI - Syphilis, human immunodeficiency virus infection, and targeting prevention. AB - To examine the interaction between syphilis and human immunodeficiency virus-type 1 (HIV-1) infection in Oklahoma, we conducted an unlinked HIV seroprevalence survey using serum specimens submitted to the Oklahoma State Department of Health for serologic test for syphilis. Of specimens with positive results from fluorescent treponemal antibody absorption test (FTA-ABS), 6.3% were HIV-1 seropositive compared to 0.8% of those that had negative results from FTA-ABS. Among specimens positive for syphilis, HIV-1 seropositivity was found almost exclusively among those from persons 20 to 39 years of age and more often among those from men than those from women (9.9% vs 1.3%). Of syphilis-positive specimens from 20- to 39-year-old men, 17.6% were HIV-1 seropositive. In Oklahoma, an area with a relatively low overall prevalence of HIV-1 infection, targeting prevention efforts to young adults who test positive for syphilis should be an efficient way to reach some persons at high risk for HIV-1 infection. PMID- 2237549 TI - Relationship between body weight and mortality in men aged 75 years and older. AB - As our population ages, recommendations about weight control in the elderly will assume increasing importance. But such recommendations are not supported by the literature, in that there is little information about the independent effect of obesity on survival in subjects who are more than 70 years old. We studied body weight, as assessed by Quetelet's index (weight in kilograms divided by the square of the height in meters), in 162 men aged 75 to 98 years (mean age = 81 +/ 5.3). Length of follow-up averaged 28.6 months. Early deaths (those occurring within the first year of the study) were attributed to preexisting morbid conditions. Cox regression was determined for the entire group, and then for the same group with early deaths excluded. Covariates were Quetelet's index, age, race, history of cigarette smoking, glucose intolerance, and hypertension. Two variables, a low Quetelet's index and glucose intolerance, were significantly associated with decreased survival for the entire group. When early deaths were excluded, however, the only variable significantly related to survival was age. These data suggest that the inverse relationship of body weight to mortality in aged men is due to preexisting morbid conditions and that when these morbid conditions are accounted for, body weight is not significantly related to survival. Hence, the relationship between body weight and mortality risk in aged men differs substantially from that in younger adults. PMID- 2237550 TI - Prevalence of previously undiagnosed hypothyroidism in residents of a midwestern nursing home. AB - Hypothyroidism in the elderly may be associated with nonspecific symptoms. To determine the prevalence of undiagnosed hypothyroidism in residents of a skilled nursing facility, we screened 434 male and 137 female residents, aged 60 years or older, for thyroid dysfunction. Overt hypothyroidism was found in three men and two women. Subclinical hypothyroidism was diagnosed in 42 men (9.7%) and 20 women (14.6%). Tests for thyroid antibodies were positive in all patients with overt hypothyroidism and in 12 (34%) of the 35 men and 12 (67%) of the 18 women with subclinical hypothyroidism who had thyroid antibody testing. All residents with newly diagnosed overt hypothyroidism and 54 (87%) of the 62 with subclinical hypothyroidism had been under medical observation for 1 year or longer. The institutionalized elderly should be screened for hypothyroidism because this abnormality may otherwise remain undiagnosed. The detection of subclinical hypothyroidism is important, as affected individuals are at risk for further decline in thyroid function. PMID- 2237551 TI - Complications of extracorporeal membrane oxygenation in neonates. AB - In cases of severe respiratory failure, cardiopulmonary bypass has been used as support until cardiac and pulmonary recovery occurs. We report the Wilford Hall USAF Medical Center experience with extracorporeal membrane oxygenation (ECMO) and its associated complications. From July 1985 to March 1989, 57 neonates were placed on membrane oxygenators. The overall survival was 79%. Technical complications encountered included catheter-related problems, mechanical complications of the pump apparatus, and hemorrhage. Hemorrhagic complications were the most frequent and devastating complications encountered. Intracranial hemorrhage accounted for six deaths associated with bypass. Extracorporeal membrane oxygenation is successful in significantly improving survival of neonates whose predicted mortality approaches 100% with conventional treatment. The rate of infant mortality using the membrane oxygenator is not affected by technical complications related to catheter position, mechanical problems with the circuit, or hemorrhage, excluding intracranial hemorrhage. The major cause of death of infants receiving extracorporeal membrane oxygenation is the underlying disease process leading to cardiopulmonary failure. PMID- 2237552 TI - Mitral valve prolapse: comparison of diagnosis by physical examination and echocardiography. AB - To determine how well physical examination findings suggestive of mitral valve prolapse (MVP) correlate with echocardiographic evidence of MVP, we retrospectively reviewed the charts of 104 patients referred to an Air Force Cardiology Clinic for echocardiography to rule out MVP. In each case, the referring physician's specialty and his findings on cardiac physical examination were recorded. All patients had M-mode echocardiography, and half of the patients had two-dimensional echocardiography. Sensitivities, specificities, and likelihood ratios for the physical examination were calculated using echocardiography as the comparison standard. The combination of a systolic click and a systolic murmur was the physical examination finding most predictive of echocardiographic MVP, with a positive likelihood ratio of 2.43. Other combinations of physical findings yielded likelihood ratios close to 1. No differences were found based on the specialty of the examining physician. We conclude that when practicing physicians find a systolic click and murmur, MVP is likely to be present on echocardiography, though one third of the patients will have normal echocardiograms. Other combinations of physical findings are of little help in predicting echocardiographic MVP. PMID- 2237553 TI - Primary prevention of coronary artery disease through a family-oriented cardiac risk factor clinic. AB - Primary prevention of coronary artery disease in children and young adults is important and can be instituted through a family-oriented cardiac risk factor clinic. Such a clinic was initiated at the Medical College of Georgia in March 1988. Children whose total cholesterol level (TC) exceeded 200 mg/dL when screened by their primary care physician were referred with their siblings and parents for fasting lipid profile and further evaluation. Data are available for the initial 21 families, including 30 children and 36 adults. The mean TC level was 258 mg/dL for index cases, 195 mg/dL for siblings, and 233 mg/dL for parents. Follow-up data obtained after therapy at a mean of 6 months are available for 12 families, including 14 children and 14 adults. The mean change in TC was from 265 to 246 mg/dL; 82% of the patients had a decrease in TC. Only one index case was documented as having neither a sibling nor a parent with an elevated cholesterol level. Family-oriented cardiac risk factor clinics are important for the identification and treatment of hypercholesterolemia in asymptomatic young people when primary prevention is possible. PMID- 2237554 TI - Analysis of the two-team approach to anterior spinal fusion. AB - An anterior approach to the spine via a thoracoabdominal incision offers the surgeon many advantages. The major vascular structures are visualized, stabilization of a long segment of the spine is strong, and recovery is speedy. Nevertheless, this is a major operation and one with potential morbidity and mortality. At Children's Hospital of New Orleans, the Pediatric Surgery and Pediatric Orthopedic Surgery Services work together to reduce these risks and in so doing maintain an acceptable morbidity. With this two-team approach; we operated on the spines of 39 patients between 1978 and 1988. The most common indications for operation included idiopathic scoliosis, neuromuscular disease, and congenital abnormalities. A thoracoabdominal approach was used in 32 patients, a thoracic approach in four patients, and an abdominal approach in three patients. Twenty-nine patients experienced 65 complications; 45 of these complications were respiratory in nature. There were no postoperative deaths. Factors unrelated to the incidence of postoperative complications included age, volume of crystalloid infused during operation, volume of blood replacement, and length of anesthesia. PMID- 2237555 TI - Pursuing mild elevations of liver enzyme values to exclude hemochromatosis. AB - To determine whether physicians in an academic medical center excluded hemochromatosis as a diagnosis in a population of patients with mildly elevated liver enzyme values, we reviewed 100 charts of patients with both aspartate aminotransferase and alkaline phosphatase levels that were less than twice the upper limit of normal. We analyzed each chart to determine if hemochromatosis would have been excluded by a subsequent workup. Those patients who did not have a complete workup were assigned to one of three categories: (1) no mention was made of abnormal liver enzyme values; (2) liver enzyme values were ascribed to some condition other then hemochromatosis and no definitive workup was done; and (3) the condition of the patient was so poor that assessment did not seem indicated. Ninety of 100 patients were not given a workup to exclude hemochromatosis. Physicians often ignore mild elevations in liver enzyme values. PMID- 2237556 TI - Survey of Alabama physicians' use of mammography, 1989. AB - In early 1989 we surveyed by questionnaire Alabama primary care physicians (N = 1800) concerning their attitudes toward and use of mammography. There were 681 respondents (37.8%). The majority (83%) recommend mammograms for their patients according to the American Cancer Society guidelines and obtain baseline studies in asymptomatic women between the ages of 35 and 40 years. It appears that the cost of mammograms is decreasing in Alabama; a screening study was available for $50 or less to 34% of responding physicians. Almost one half (48%) of the physician respondents believe that more than 50% of their patients have had at least one mammogram. PMID- 2237558 TI - New drug and biologic product approvals in 1989. PMID- 2237557 TI - Tamoxifen therapy for painful idiopathic gynecomastia. AB - We have evaluated the efficacy of the antiestrogen tamoxifen in six men with painful idiopathic gynecomastia. Subjects were given either tamoxifen or placebo for 2 to 4 months and then were given the other agent for an identical period. Breast size was considered to have been reduced only if it had decreased by one or more Marshall-Tanner stages during the treatment period. Pain reduction with tamoxifen therapy was statistically significant for the group, occurring in five of six subjects during tamoxifen treatment and in only one of six during the placebo period. Size reduction with tamoxifen was only marginally significant for the entire group, but occurred in all three subjects who were initially in Marshall-Tanner stage III and in none of the three subjects who were initially in stage V. During tamoxifen treatment, there was a significant increase in the serum levels of luteinizing hormone and total estradiol and a marginally significant increment in the total testosterone level. PMID- 2237559 TI - Surgical literature and "surgispeak": a critique. PMID- 2237560 TI - Normeperidine-induced seizures in hereditary coproporphyria. AB - Seizures are common in acute exacerbations of hepatic porphyria, even though the etiology is not identified in most cases. We have reported a case of normeperidine-induced seizures in a patient with hereditary coproporphyria. Although meperidine is commonly used for pain control during acute attacks in these patients, this report suggests that meperidine is not a good analgesic choice in porphyria. Normeperidine-induced seizures in patients with porphyria may be treated by withdrawal of meperidine therapy and selective use of anticonvulsants. PMID- 2237561 TI - Pneumocystis carinii pneumonia manifested as a hilar mass and cavitary lesion: an atypical presentation in a patient receiving aerosolized pentamidine prophylaxis. AB - A case of Pneumocystis carinii pneumonia (PCP) in a patient with AIDS was manifested radiographically as a hilar mass and cavitary lesion. The patient had been receiving aerosolized pentamidine as prophylaxis against PCP. Nonuniform deposition of aerosolized pentamidine was probably responsible for this atypical radiographic appearance of PCP. PMID- 2237562 TI - Achromobacter xylosoxidans: a drug-resistant pathogen in newborns and immunocompromised patients. PMID- 2237563 TI - Postural hypotension: pressor effect of octreotide not mediated by norepinephrine. AB - Orthostatic hypotension of the Shy-Drager syndrome is a chronic incapacitating condition characterized by lack of an appropriate increase in the plasma norepinephrine level in response to standing. Recently, the somatostatin analogue octreotide has been reported to induce a pressor response in patients having this syndrome. We have reported a case of Shy-Drager syndrome in which octreotide was effective, but the rise in blood pressure was not accompanied by an increase in the plasma norepinephrine level. Hence, the pressor effect of octreotide is not mediated by stimulation of the sympathetic nervous system, but probably through splanchnic vasoconstriction. PMID- 2237564 TI - Synchronous Hodgkin's disease and myelofibrosis terminating with granulocytic sarcoma and acute megakaryocytic leukemia. AB - Our patient had stage IIIAI Hodgkin's disease with synchronous myelofibrosis and myeloid metaplasia. A slowly progressive myeloproliferative disease developed over 9 1/2 years and terminated in a painful osteolytic bone disease, spinal extradural granulocytic sarcoma and acute megakaryocytic leukemia. It is likely that this was a result of the myeloproliferative disease rather than a late complication from combination chemotherapy. Our case demonstrates the importance of a curative approach to Hodgkin's disease even in the face of a coexistent disease with a long or unknown natural history. PMID- 2237565 TI - Cytophagic histiocytic panniculitis evolving into total lipodystrophy. AB - A 15-year-old boy had persistent fever with severe neutropenia, thrombocytopenia, coagulation disorder, and marked elevation of lactate dehydrogenase values. A diagnosis of cytophagic histiocytic panniculitis was made after repeated skin biopsies. Three years after onset, he gradually lost 20 kg in body weight, and both skin and bone marrow specimens revealed degenerative changes of fatty tissue without any inflammatory cells. These findings suggest that total lipodystrophy syndrome results from the inflammatory destructive process of adipose tissue. To our knowledge, our report is the first to show, in a series of histologic studies, that an inflammatory destructive process may be involved in some cases of total lipodystrophy syndrome. PMID- 2237566 TI - Isolated erythroid hypoplasia and renal insufficiency induced by long-term griseofulvin therapy. AB - We describe a patient with hematuria, pyuria, eosinophiluria, decreased renal function, and severe anemia that developed while she was receiving chronic therapy with griseofulvin for onychomycosis. We offer evidence that griseofulvin can cause an isolated erythroid hypoplasia and possibly an allergic interstitial nephritis. This is the first documented case of the above entities induced by the agent. We would recommend, based on our report, that otherwise healthy patients, when maintained on the drug for extended periods of time, have periodic determinations of renal function and hematologic status. As drug-induced erythroid hypoplasia typically occurs after a relatively long period of dosing, it may be prudent in certain individuals to monitor the CBC at approximately bimonthly intervals after initiation of therapy. Recommendations regarding monitoring of renal function are more difficult, as acute allergic interstitial nephritis can occur after either short- or long-term exposure to certain drugs. PMID- 2237567 TI - Hypercalcemia as a clinical prodrome to lymphoma. AB - A 73-year-old man was admitted for evaluation of unexplained hypercalcemia and was found to have a large-cell non-Hodgkin's lymphoma with stage IV disease. Treatment with cyclophosphamide, doxorubicin (Adriamycin), vincristine sulfate, and prednisone chemotherapy returned his calcium levels to normal. Hypercalcemia with lymphoma is rare, and persistent evaluation for malignancy is essential. PMID- 2237568 TI - Arteriovenous malformation of the tongue. AB - Polyvinyl alcohol particles used to embolize an arteriovenous malformation of the tongue were only temporarily successful. Additional embolization therapy was necessary and was complicated by ischemic ulcers of the tongue. We conclude that embolization therapy can be used, but the efficacy of this therapy in the longer term remains to be determined. PMID- 2237569 TI - Pseudohypoglycemia in adult victims of adolescent incest. AB - Two patients with complaints of hypoglycemia came for evaluation, and both complained of intermittent episodes of mental dullness, disorientation, confusion, and palpitations relieved by eating. Plasma glucose levels at the time of symptoms were always above 70 mg/dL. Initial onset of symptoms was within 1 to 2 years after cessation of repeated incest, and on recognition of this, both patients associated the onset of episodes of similar feelings with the acts of incest. Recognition of this connection did not decrease the frequency of episodes. Both persistently refer to the episodes as "hypoglycemia" despite recognition that no glucose level below 70 mg/dL has been recorded during an episode. Recurrent episodes of derealization and depersonalization in both patients appear to be sequelae of adolescent incest experiences, but these patients cling to the label "hypoglycemia," perhaps in part because they are unwilling to accept a psychiatric diagnosis for their episodes. PMID- 2237570 TI - Neurologic abnormalities in a patient with human ehrlichiosis. AB - Human ehrlichiosis is a tick-borne rickettsial disease characterized by fever, headache, myalgias, anorexia, and occasionally rash. In our patient, changes in mental status, upper motor neuron signs, cerebrospinal fluid pleocytosis, and increased serum protein levels were found in association with serologically confirmed ehrlichiosis and were most likely due to vasculitis involving the central nervous system. Intraleukocytic inclusions, although observed in our case, have been infrequently found in other reported cases of ehrlichiosis. PMID- 2237571 TI - Acute obstructive jaundice in the multiple trauma patient. AB - The appearance of acute jaundice in the multiple trauma patient may result from obstruction of the common bile duct by clot. Management of this problem may be hindered by a delay in diagnosis, especially where alterations in pigment load and hepatic clearance may have produced the jaundice. A high index of suspicion combined with the judicious use of various noninvasive imaging modalities may be helpful in making the diagnosis. The progression of jaundice in a patient suspected of having acute obstructive hemobilia should prompt rapid operative intervention. At laparotomy, cholangiography or common bile duct exploration should be done. Persistent bleeding should be managed initially with angiographic localization and transcatheter embolization; its failure would necessitate surgical control of the source. PMID- 2237572 TI - Traumatic diaphragmatic hernia and intestinal obstruction due to penetrating trunk wounds. AB - We have reported two cases of intestinal obstruction due to traumatic diaphragmatic hernia, both resulting from apparently trivial knife wounds. When TDH is due to a penetrating injury, it tends to produce symptoms of intestinal obstruction. A high index of suspicion, a chest x-ray film, and barium studies of the gastrointestinal tract are usually needed to make the diagnosis, though CT scans, ultrasonography, laparoscopy, and radionuclide scanning may also be useful. Surgeons and emergency physicians should be aware of the potential for TDH when there is a history of a penetrating wound of the chest or abdomen. PMID- 2237573 TI - Adenocarcinoma of the appendiceal stump. AB - We have reported the case of a 58-year-old woman with nonspecific abdominal complaints in whom barium enema and subsequent colonoscopy showed a 3 cm lobulated adenocarcinoma within a villous adenoma arising from the appendiceal stump. Because such appendiceal malignancies have no specific clinical signs, symptoms, or radiologic features, preoperative diagnosis is extremely difficult, and colonoscopy may be required to clarify radiologically demonstrated irregularities. PMID- 2237575 TI - Left ventricular pseudoaneurysm complicating mitral valve replacement in a 4-year old child with acute bacterial endocarditis. AB - A 4-year-old child with acute bacterial endocarditis required mitral valve replacement. A left ventricular pseudoaneurysm developed following surgery. The etiology and diagnosis of this complication are discussed. PMID- 2237574 TI - Trabecular or Merkel's cell carcinoma. AB - Two cases of trabecular cell carcinoma of the skin are presented. The clinical presentation and behavior, and the histologic findings, of the tumor are described. Surgical excision of the primary lesion with regional lymph node dissection, if indicated, is the treatment of choice. Distant metastasis is treated by local irradiation. PMID- 2237576 TI - Peripartum myocardial infarction from presumed Kawasaki's disease. PMID- 2237577 TI - Adenocarcinoma of the colon occurring with intussusception in an adolescent. AB - Hydrostatic reduction of intussusception is definitive therapy in most infants with this abnormality. In the older child, adolescent, and adult, a polyp or tumor is often present. Operative intervention should be considered earlier in the clinical course both to relieve the intussusception and to define the nature of the lead point. PMID- 2237578 TI - Pleuropulmonary tularemia: successful treatment with erythromycin. AB - A 64-year-old man had community-acquired pneumonia that was retrospectively diagnosed as pleuropulmonary tularemia. He was successfully treated with erythromycin. We review the case and briefly discuss the literature on this point. PMID- 2237579 TI - Medicare and MAAC. PMID- 2237580 TI - Bad X-ray reports. PMID- 2237582 TI - Health status and urban poverty. PMID- 2237581 TI - Atenolol and retroperitoneal fibrosis. PMID- 2237583 TI - Molecular technology: improving strategies for controlling hydatid disease and cysticercosis. AB - Recombinant DNA and related technologies are providing valuable, novel reagents for application in control strategies against the major parasitic diseases, including hydatid disease and cysticercosis. The impact of these powerful techniques for improving diagnosis and identification of various life cycle stages of Echinococcus spp. and Taenia solium, essential pre-requisites for epidemiological studies and for evaluating control programs, is beyond question. Furthermore, the use of molecular technology for characterizing sub-specific variants of strains of both Echinococcus and T. solium has led to important revisions of our understanding of the diseases they cause. In light of the recent remarkable development of a recombinant vaccine against T. ovis, the first practical parasite vaccine to be produced, the prospects for rapid development of similar vaccines against the medically important taeniids appear to be very encouraging. PMID- 2237584 TI - Epidemiological study of sulfonamide and trimethoprim resistance genes in Enterobacteriaceae. AB - Sulfonamide (Su) and trimethoprim (Tp) resistance are known to caused by the production of drug resistant dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR), respectively. Sulfonamide and trimethoprim are often used in combination under the name cotrimoxazole. Cotrimoxazole resistance in various enteric bacteria isolated at Ramathibodi Hospital was studied. The rate of resistance from 1984-1989 of many genera was rather constant at 40%-60% except in Shigella spp in which the rate increased rapidly in 1987 till 1989. Seventy-five percent of Su-Tp resistant (Sur-Tpr) bacteria were also found to be resistant to other drugs such as ampicillin, aminoglycosides, tetracycline and chloramphenicol in addition to cotrimoxazole. Two hundred and forty Su-Tp resistant strains were analysed for the presence of type I and II dihydropteroate synthase as well as type I and V dihydrofolate reductase genes by hybridization with the corresponding gene probes. Type I DHPS gene predominated in Su-Tp resistant bacteria at 60.8% whereas type II DHPS was found in only 25%. Some strains (11.7%) had both genotypes but 2.5% did not have any. In the trimethoprim resistance study, the DHFR type I gene was also found more frequently (30%) whereas type V DHFR was only 19%. The remaining of Tp resistance (51%) was unclassified. The coexistence of Su and Tp resistance genes of each type was investigated among 118 Su and Tp resistant strains. It was found that type I DHPS gene was found together with either type I or V DHFR gene and type II DHPS was found with type I DHFR gene at about the same rate (28.9%, 27.1% and 26.3%, respectively). However, the presence of type II DHPS together with type V DHFR was rather low, only 5.9% of isolates were found to have both types of genes. PMID- 2237585 TI - Drug resistance of Haemophilus ducreyi. AB - Chancroid, the disease caused by H. ducreyi is one of the common sexually transmitted diseases (STD) in Thailand and other tropical countries. In Thailand, the diagnosis of chancroid is still based on clinical appearance which may be confused with other STD manifested by genital ulcers. In recent years the increasing resistance strains of H. ducreyi to these antimicrobial agents has been reported so that cultivation and antimicrobial susceptibility tests of this organism have become more important. This study showed that MBV is the best medium for isolation with a success rate of 48%. All strains tested from isolates of this study were resistant to ampicillin, due to production of beta-lactamase. Approximately 99% of the strains were resistant to tetracycline 92% of strains were resistant to sulfamethoxazole and 32% were resistant to trimethoprim. All isolates were susceptible to chloramphenicol, ceftriaxone, erythromycin and the fluorinated quinolones ciprofloxacin, norfloxacin, ofloxacin and pefloxacin. Beta lactamase enzymes produced by 37 strains of H. ducreyi were determined for their isoelectric point (pI). All had pI of 5.4, indicative of plasmid-mediated beta lactamase type TEM-1. PMID- 2237586 TI - Haemophilus influenzae and Streptococcus pneumoniae in children with acute respiratory infection. AB - The incidence of Haemophilus influenzae and Streptococcus pneumoniae in children with acute respiratory infection (ARI) under 5 years was carried out by throat swab culture, blood culture, body fluid or tissue culture in 688 patients from a community, 744 patients from a teaching hospital in Bangkok, 766 normal children from the community and 303 children from a hospital well baby clinic. H. influenzae was found in the throats of 15-20% of patients and in the throats of 4 6% of normal children (p less than 0.001 for both hospital and community patients). Only 12/332 strains (3.6%) of H. influenzae were type b. The rest of H. influenzae were non type b. The most common biotype of H. influenzae non type b was biotype II. S. pneumoniae was found in hospital patients in highly significant numbers compared to the controls (12% vs 4%). No significant difference was observed in strains from the community patients. PMID- 2237587 TI - The use of a coagglutination test to presumptively identify Salmonella typhi in bone marrow-oxgall medium cultures from typhoid fever patients. AB - A study was conducted to test a coagglutination procedure for detection of Salmonella typhi in bone marrow cultures from suspected typhoid patients admitted to Friendship Hospital, Jakarta, Indonesia. The results of the coagglutination tests were compared to the results from standard cultural isolation and identification. Bone marrow aspirates (356) were cultured in oxgall medium and aliquots subcultured daily for 7 days while simultaneously testing for the presence of Salmonella group D and Vi antigens using coagglutination (COAG). S. typhi was isolated from 220 (62%) of the cultures and the D- and Vi-COAG tests were positive for those same cultures. The COAG test was also negative for 6 cultures containing S. paratyphi A. The COAG results were available within 10 minutes after 18 to 24 hours incubation of the primary cultures whereas the isolation and confirmed identification took 2 to 3 days longer. The COAG test is valuable as an aid to rapidly identify S. typhi in bone marrow-oxgall cultures. PMID- 2237588 TI - Prevalent serogroups and antimicrobial susceptibility of Shigella strains in Metro Manila, 1982-1988. AB - From 1982 to 1988, Shigella was detected in 4% of stool specimens cultured at The Research Institute for Tropical Medicine (RITM), Manila. S. flexneri was the most prevalent serogroup with 2a, 1b and 1a as the predominant serotypes. Isolation was most frequent during the July to December period. Drug resistance was most often observed in S. flexneri with serotype 2a exhibiting resistance to the combination of ampicillin, chloramphenicol, tetracycline and streptomycin. More multiple-drug than single-drug resistant strains were observed for the last four years. Ampicillin is still the most frequently used drug for most forms of shigellosis in the Philippines. However, the demonstration of increasing resistance among the isolates studied in RITM underscores the need to monitor antibiotic susceptibility studies and document the emergence of resistant strains in the entire country. PMID- 2237589 TI - Occurrence of beta-hemolytic streptococcus group G in school children and sick children. AB - We studied the occurrence of Streptococcus group G in throat cultures obtained from school children of poor socioeconomic status and in sick children brought to our hospital. The results revealed a high occurrence of group G Streptococci (44% and 91.5% respectively) in cases positive for beta-hemolytic Streptococci. PMID- 2237590 TI - Relationship of vibriocidal antibodies to history of cholera vaccination in Thai adult volunteers. AB - Vibriocidal antibodies were determined by microtechnique in 5 groups of Thai adult volunteers who had never received or had received cholera vaccination within one year, more than one to five years ago, more than five to ten years ago and more than ten years ago respectively. Detailed questionnaires about socioeconomic status, educational levels and environmental factors were presented to every volunteer. There were no differences statistically in incomes, educational levels and environmental factors among the groups. It was found that the reciprocal geometric mean titers of antibodies in volunteers who had never received cholera vaccination was generally low. The reciprocal geometric mean titers of the volunteers who had received cholera vaccination within one year were statistically different from other groups (p = 0.05). There was no correlation between blood groups of volunteers and vibriocidal antibodies. PMID- 2237591 TI - The species of green pit viper in Bangkok. AB - The aims of this study were to delineate the species of Green pit viper and clinical patterns in Bangkok areas. This study was a blind independent comparison. Among 188 Green pit vipers collected only two species, i.e. Trimeresurus alborabris and T. macrops were found. There were no differences in snake sizes and in clinical patterns of snake bite. The majority of the clinical cases (90.1%) was classified as of mild degree of severity and severe envenomation was observed only in T. alborabris victims. The ratio between T. alborabris and T. macrops victims in Bangkok residents was 1.7:1 but the ratio was reversed in Thonburi residents. PMID- 2237592 TI - Characterization of a monoclonal antibody that neutralizes the hyaluronidase activity of Russell's viper venom. AB - Three monoclonal antibodies (WPN1, WPN2 and WPN3) raised against a partially purified fraction of Russell's viper venom (RVV) were characterized. All three monoclonal antibodies reacted with crude RVV when tested by ELISA, but only two (WPN1, WPN2) neutralized its hyaluronidase activity. WPN1 was the more potent and was effective at an antigen: antibody ratio of 1:3. Furthermore, WPN1 was shown to recognize only the 14,000 MW component of crude RVV. This has been identified in a previous study to be hyaluronidase. This antibody was also found to recognize some components of Calloselasma rhodostoma venom which also possesses potent hyaluronidase activity. The potential therapeutic role of antibodies that neutralize the hyaluronidase component of snake venoms should be investigated further. PMID- 2237593 TI - Competitive antibody binding inhibition ELISA for the detection of Plasmodium falciparum antigen. AB - A competitive antibody binding inhibition ELISA to detect Plasmodium falciparum infected cells in clinical specimens was developed. Optimum conditions developed included: 12.5 micrograms/ml of P. falciparum antigen for plate coating, 25 micrograms/ml of polyclonal rabbit anti-P. falciparum IgG, 30 minute incubation of a mixture of infected red blood cell extract with anti-P. falciparum IgG, dilution of 1:500 of alkaline phosphatase-conjugated anti-rabbit IgG, and reading of the absorbance values 60 min after adding the p-nitrophenyl phosphate substrate. Reproducibility of the assay against cultured P. falciparum-infected red blood cells varied according to parasitemia, the higher the parasitemia, the better the reproducibility. The sensitivity of the assay was approximately 110 parasites/10(6) red blood cells. The assay was applied to field conditions involving 103 cases with falciparum malaria, 38 cases with vivax malaria and 30 healthy controls. With the 10% antibody binding inhibition as a cutoff, 87.4% of falciparum cases and 26.3% of vivax cases were positive. After treatment, the majority of cases became parasitologically negative with the corresponding negative assay. Regression analysis showed only weak but statistically significant correlation between the percent inhibition with parasitemia (r = 0.38, p less than 0.001), and this was more clearly shown in patients with high parasitemia. PMID- 2237594 TI - Cardiac involvement in beta-thalassemia/hemoglobin E disease: clinical and hemodynamic findings. AB - Clinical and hemodynamic studies were conducted in 6 women and 2 men with beta thalassemia/hemoglobin E disease. All except one had splenectomy. The patients were hospitalized in the state of congestive heart failure. The systemic blood pressure was low or normal. The electrocardiograms revealed normal sinus rhythm in all, right axis deviation in some, right atrial enlargement in the majority and repolarization abnormalities in some. The echocardiograms were sensitive to detect the right heart abnormalities and pericardial effusion. Cardiac catheterization disclosed moderate to marked hypoxemia. All patients except one had pulmonary hypertension. Some had left ventricular dysfunction. From this study. It is concluded that right heart involvement secondary to diffuse pulmonary thromboembolic disease is a major complication of beta thalassemia/hemoglobin E disease. PMID- 2237595 TI - Fecal egg output in relation to worm burden and clinical features in human opisthorchiasis. AB - A study of the relation of fecal egg excretion to worm burden and clinical features was carried out in 45 opisthorchiasis patients who had no signs of biliary obstruction. The fecal egg excretion was consistent and correlated with the worm burden. Although there was no definite association between clinical signs and intensity of infection, mild hepatomegaly and thickened wall or dilatation of the gallbladder were found more commonly in heavily infected patients. Eosinophilia was observed more often than previous reports. Concomitant parasitic infections were found in 82% of the patients. After praziquantel treatment, egg counts increased greatly during the first few days then decreased to very low levels in 7 days. PMID- 2237596 TI - Isolation of indigenous larvicidal microbial control agents of mosquitos: the Malaysian experience. AB - A nationwide screening program searching for microbial control agents of mosquitos was initiated in Malaysia in 1986. A total of 725 samples were collected and 2,394 bacterial colonies were isolated and screened for larvicidal activity. From such screening, 20 Bacillus thuringiensis, 6 B. sphaericus, 1 Clostridium bifermentans and 2 Pseudomonas pseudomallei larvicidal isolates were obtained. Of these, a new B. thuringiensis named as subspecies malaysianensis was found, while the C. bifermentans was also a new anaerobe individualized as serovar malaysia. It was concluded that this screening program was highly successful. PMID- 2237597 TI - Health status of children living in a squatter area of Manila, Philippines, with particular emphasis on intestinal parasitoses. AB - In 1988 a study was performed in a squatter area of Manila, Philippines. Three substudies were carried out: (1) an analysis of the reported health situation and the available health services for the population of Smokey Mountain, (2) a vaccination coverage survey and (3) a cross-sectional stool sample survey. Respiratory infections, diarrhea, measles and malnutrition were the most frequently reported causes of ill-health and death. Not only governmental but also various non-governmental health services have been developed over the last few years. Better coordination and cooperation between the various health care providers, furtherance of community participation, improvements in the performance of the community health volunteers and stronger emphasis on preventive health care (such as health education) are suggested. The vaccination coverage cluster survey performed among children aged 1-2 years revealed that 24% of the surveyed children were fully immunized and 19% not immunized at all. The drop-out rates of children vaccinated through non-governmental organizations were significantly lower than those of the children vaccinated through a governmental agency. The cross-sectional stool sample survey performed among 238 children aged 8 months to 15 years revealed that 96% of the surveyed children were harboring intestinal parasites. Most common was Trichuris and Ascaris. The prevalence of hookworm was 10%, and those of Entamoeba histolytica and Giardia lamblia 21% and 20%, respectively. Most children (84%) were affected by multiparasitism. The need to adapt the concept of Primary Health Care to the context of the urban poor and not only to provide health services but also to change social and economic conditions is emphasized. PMID- 2237598 TI - Sexual behavior of Filipino female prostitutes after diagnosis of HIV infection. AB - A study of female prostitutes in Manila who tested positive for human immunodeficiency virus (HIV) antibody ascertained demographic and sexual behavior information following diagnosis. Counselling alone did not appear to have a major impact on the sexual behavior of the HIV positive women since most continued to work as prostitutes. Switching from high risk to low risk jobs in bars is not effective in preventing HIV positive women from engaging in prostitution. Revoking work permits is only effective if enforced with adequate follow up. Alternative job training programs may offer a viable approach. PMID- 2237599 TI - Behavior of urban based child caretakers in the home treatment of diarrheal diseases. AB - Behaviors of low income urban mothers and child caretakers in the treatment of childhood less than 5 year diarrhea were analysed from a surveillance study conducted between August 1988 and July 1989. Help seeking behaviors of mothers and caretakers for 412 episodes of child diarrhea were as follows: investigators 37.1%, drug stores 18.2%, wait and see or self treatment 17.0%, private clinics 12.6%, near by hospital 10.2%, and local health center 4.9%. Major treatment practices included ORT alone (54%) and ORT plus antibiotics and/or antidiarrheal drug (22%). Overall ORT usage was 76%. Twelve percent of diarrheal episodes no treatment was given to the children. Antimicrobials were believed to be essential in addition to ORT especially when diarrhea was associated with fever, vomiting and bloody stools. Thirty-six percent of invasive diarrhea cases (Shigella, Salmonella, Campylobacter) were treated with antibiotics. Only 18.2% of noninvasive diarrhea received antibiotics, most of this antibiotic use being in rotavirus diarrhea where vomiting and some fever are prominent. Availability of oral rehydration salts (ORS) and good experience with ORT were the key to the extensive use or ORT in this study. A surprisingly small number of mothers and child caretakers (4.9%) sought help from the local health center when their children had diarrhea. PMID- 2237600 TI - Acquired aplastic anemia in children: a review of 100 patients. AB - A retrospective study of acquired aplastic anemia in 100 Thai children treated with testosterone and prednisolone during 1969 to 1987 is reported. The age ranged from 3-14.5 years (mean 10.3 years). The male to female ratio was 2.3:1. The duration of follow up ranged from 1-17 year (mean 5 years). Prior exposure to possible etiologic agents was found in 36% : antipyretics, Ya-chood, insecticides, benzene, chloramphenicol and paint. The presenting symptoms were bleeding and anemia 72%, fever with either bleeding or anemia 28%. The common sites of bleeding were purpura, epistaxis, gum and teeth, and the gastrointestinal tract. All patients received appropriate supportive treatment and testosterone combined with prednisolone. The results of treatment were evaluated in 80 cases who were followed up until death or at least one year after the diagnosis. Two-thirds of the patients presented with laboratory findings similar to severe aplastic anemia; the fatality rate was 50% (40/80). Most of them succumbed to infection or bleeding in the first 6 months after diagnosis. The recovery rate was 50% with complete, partial and initial responses in 28%, 17% and 5% respectively. The late malignancy rate was 2%. For severe aplastic anemia or for patients who have poor prognostic factors, early approaches of bone marrow transplantation or antilymphocyte globulin administration should be considered. PMID- 2237601 TI - Giardiasis coinciding with cryptosporidiosis in an immunocompetent patient with protracted watery diarrhea. PMID- 2237602 TI - Immune function in a case of endemic malaria with sinus histiocytosis with massive lymphadenopathy. PMID- 2237603 TI - Self-esteem and depression. II. Social correlates of self-esteem. AB - The Self-Evaluation and Social Support Schedule (SESS), an interview-based instrument, is described, which aims to give a comprehensive description of a person's social milieu in terms of 'objective' and 'subjective' measures. On the basis of a population survey of 400 largely working-class women, a tentative causal model is developed which relates both the quality of current interpersonal ties and childhood experiences to current negative and positive measures of self esteem. A major purpose of the exercise is to develop positive and negative indices of the social environment that can be used to elucidate the aetiological role of self-esteem in the development of depression. This is the task of a third paper. PMID- 2237604 TI - Self-esteem and depression. III. Aetiological issues. AB - This is the last of a series of three papers dealing with the role of self-esteem in the onset of clinical depression. On the basis of a longitudinal population enquiry a comprehensive psychosocial model of depression is developed. It is concluded that self-esteem (primarily in terms of a negative measure) does play a significant role. However, this can be only properly interpreted in the light of the full model. This highlights: 1. the importance of the occurrence of both a negative environmental factor (negative interaction with children or husband for married or negative interaction with children or lack of a very close tie for single mothers) and a negative psychological factor (low self-esteem or chronic subclinical condition); and 2. how a relatively small group of high risk women in these terms (23% of total at risk based on measures collected well before any onset) contain three-quarters of all instances of onset of depression occurring over a 12 month period. PMID- 2237605 TI - Self-esteem and depression. IV. Effect on course and recovery. AB - The present paper, the fourth and last in a series examining the role of self esteem in depressive disorder in the general population, deals with recovery/improvement from a disorder at a case level. Both positive evaluation of self (PES) and absence of negative evaluation of self (NES) measured during a chronic episode are related to subsequent recovery or improvement. A causal effect is suggested since the measure adds over and above to that of environmental factors previously established to relate to recovery/improvement- the reduction of an ongoing difficulty or fresh-start event. Positive evaluation of self was also related to recovery/improvement from subsequent onsets of case depression. In this instance, unlike that for the chronic conditions, self-esteem was measured outside the episode of depression. A causal effect was also suggested because it made an independent contribution vis-a-vis the effect of fresh-start events. Given the small size of the sample the study should be seen as an exploratory one. PMID- 2237606 TI - The Mannheim Interview on Social Support. Reliability and validity data from three samples. AB - Social support questionnaires usually provide scant information about the members of supporting networks, while network-analytical approaches often fail to sufficiently detail the functional aspects of social support available to an individual. A structured interview, the "Mannheim Interview on Social Support" (MISS) is presented which combines the advantages of both approaches by mapping an individual's social resources in a "support matrix" of [network members] * [relationship characteristics + support functions]. Stability and validity data collected in three different samples (discharged depressed in-patients, university students, and parents of children afflicted with cancer) are reported. Test-retest correlations are compared with alternative measures of stability, and the relationship of various MISS scores to scores based on conceptually related instruments is explored. The results indicate good test-retest stability of the main functional and structural MISS scores rtt = 0.66 to 0.88 for a four-week interval, and rtt = 0.42 to 0.79 for a six-month-interval). It is shown that the MISS captures several dimensions of a person's social support environment not covered by questionnaires targeting subjective perceptions of support. PMID- 2237607 TI - Depression among Cuban Americans. The Hispanic Health and Nutrition Examination Survey. AB - This paper presents the findings on depressive symptomatology and major depressive disorder in Cuban American respondents to the Hispanic Health and Nutrition Examination Survey (HHANES). The HHANES represents the first population based assessment of the mental health status of Cuban Americans. High levels of depression, as measured by a CES-D score of 16 or more, were found in ten percent of the sample. Female gender was independently associated with CES-D caseness. The lifetime, six-month, and one-month prevalence rates of major depressive disorder, as measured by the National Institute of Mental Health Diagnostic Interview Schedule (DIS), were 3.15%, 2.12%, and 1.50%, respectively. An income level of less than ten thousand dollars was independently associated with a lifetime diagnosis of major depression. PMID- 2237608 TI - A reanalysis of the impact of non celebrity suicides. A research note. AB - Previous work on suicide and the media has neglected theoretical issues. Some work has implied that only celebrity suicides can be expected to trigger additional suicides in the real world. The present study focuses on non celebrity suicides. Correcting coding errors in a previous work, it finds that the suicides of non celebrities are associated with increases in the national suicide rate. An index of publicized celebrity suicide stories was, however, more closely associated to increases in suicide than the publicized non celebrity stories. The model explains 90 percent of the variance in monthly suicide rates. PMID- 2237609 TI - Time-series analyses of the American suicide rate. AB - A time-series study of suicide in the USA from 1940 to 1984 explored the extent to which social and economic variables could predict the actual suicide rate, the smoothed trend in the suicide rate, and deviations of the actual suicide rate from the smoothed trend. It was found that the social and economic variables were more successful in predicting the smoothed trend in the suicide rate. PMID- 2237610 TI - The GHQ-12 as a screening tool in a primary care setting. AB - The performance of the 12-item General Health Questionnaire (GHQ) was tested against a modified version of a structured diagnostic interview for making DSM III-R diagnoses, the Composite International Diagnostic Interview (CIDI), in a population of 787 primary care patients, 214 of whom were interviewed. The Yoruba versions of both instruments were found to be feasible in this setting and the inter-rater reliability of the CIDI was good. The GHQ-12 showed a sensitivity of 68% and a specificity of 70% when only cases meeting the criteria for specific DSM III-R disorders were considered. The sensitivity was better for certain individual disorders and the overall performance was marginally improved when scoring was made according to the revised method proposed by Goodchild and Duncan Jones. PMID- 2237611 TI - [Complex automatic data processing in multi-profile hospitals]. AB - The computerization of data processing in multi-disciplinary hospitals is the key factor in raising the quality of medical care provided to the population, intensifying the work of the personnel, improving the curative and diagnostic process and the use of resources. Even a small experience in complex computerization at the Botkin Hospital indicates that due to the use of the automated system the quality of data processing in being improved, a high level of patients' examination is being provided, a speedy training of young specialists is being achieved, conditions are being created for continuing education of physicians through the analysis of their own activity. At big hospitals a complex solution of administrative and curative diagnostic tasks on the basis of general hospital network of display connection and general hospital data bank is the most prospective form of computerization. PMID- 2237612 TI - [Problem of methodology of evaluation of the quality of public health]. AB - The basic general methodological assessments of public health quality are considered. An analogy is drawn with quality assessment in industry, approaches to the development of multi-aspect and multi-parameter assessment of public health quality are substantiated. A term of "qualimetry " of public health is suggested. PMID- 2237613 TI - [Sociological study of the quality of medical services]. PMID- 2237614 TI - [Educational status and life expectancy]. AB - The article provides a foundation for the necessity of studying the social differentiation of mortality, in particular the influence of educational status and character of labour on length of life. It is indicated that higher indices of length of life are found among populations with high educational status and among people engaged in intellectual pursuits. The description is given of the methodological approaches to the construction of life expectancy tables according to the educational status and character of labour. PMID- 2237615 TI - [Improving the teaching of social hygiene and public health administration]. PMID- 2237616 TI - [Planning of sampling studies of morbidity and hospitalization at large territories]. AB - This paper provides the methodological principles of planning sample survey of hospital morbidity of population at the level of large economic regions and the republic at large. Proceeding from the example of socio-hygienic study of burn injuries requiring hospital treatment, and organization of hospital care for the burned, the methods of elaborating the principles of sample surveys, the use of stratified cluster selection with optimum placing of sample units are described. The methodological scheme permits to minimize the size of the sample and to obtain representative evaluations of the needed indices at large territories. While studying 23 sample units from 796 formed in the republic, evaluations of a number of indices were obtained which virtually coincided with the indices calculated according to the total data reported. PMID- 2237617 TI - [Definition of the concept of "health-related activity"]. PMID- 2237618 TI - [Health of young people]. PMID- 2237619 TI - [Use of the main component method in complex socio-hygienic study of life style and health status of workers' families]. AB - On the basis of the survey of 350 families an analysis is made of the impact of some particular living conditions and mode of life on the families health by using the method of main components. This made it possible to range the factors - the main components according to the degree of their influence and to single out the leading ones in the formation of health. The analysis indicated that more than a half of contribution to the general dispersion of the internal structure of health phenomenon of family members is made by lifestyle factors. PMID- 2237620 TI - [Use of computers in preparing the data regarding morbidity with temporary disability]. AB - The use of "Iskra-1256", "Iskra-1030" and other kinds of computers provide a scientific and valid foundation for solving the problem of health-promoting activities among workers of timber enterprises. The findings of the study indicate that each timber enterprise has its own distinctive features, working and living conditions, organization of industrial process which determines the main causes of diseases. The complex approach to the evaluation of morbidity should provide the basis for the planing and distribution of financial resources for occupational safety and workers' health protection, placing of personnel and medical facilities. PMID- 2237621 TI - [Experience of medical institutes with the training in the field of general mass screening]. PMID- 2237622 TI - [Strokes to the portrait of N.A. Semashko]. PMID- 2237623 TI - [Physician-revolutionary V.M. Bogutskii (1871-1929)]. PMID- 2237624 TI - 1990 Volvo Award in clinical sciences. The consistency and accuracy of roentgenograms for measuring sagittal translation in the lumbar vertebral motion segment. An experimental model. AB - An experimental model of the L4-L5 lumbar motion segment was developed that allowed precise manipulation of sagittal translation, rotation of L5 relative to L4, tilt of L4 on L5, and control of roentgenogram quality (image clarity) by placing a water bath between the tube and the vertebral body. A series of experiments were designed to systematically assess the consistency and accuracy of sagittal translation measurements from roentgenograms of varying quality, using different measurement protocols and various rater combinations on models with varying degrees of concomitant motions (rotations and tilts). Study 1 assessed the effects of roentgenogram quality, raters, and seven measurement methods on the consistency and accuracy of evaluating translations in the sagittal plane. Results indicated very high reliabilities across roentgenogram quality, raters, and measurement. As expected, high-quality roentgenograms were more accurately evaluated than lower-quality roentgenograms. However, closer inspection of the consequences of errors in measured translations indicated surprisingly high false-positive and false-negative rates, with significant differences observed between measurement methods. Study 2 assessed the effects of concomitant motions and measurement methods on the consistency and accuracy of evaluations. Within-rater consistency and accuracy indices were remarkably high and similar across measurement methods and degrees of concomitant motions. However, important differences in the false-positive and false-negative rates were again observed. Method 2, described by Morgan and King, demonstrated the overall best performance and the least interference due to concomitant motions. Study 3 assessed the effects of raters and measurement methods on the consistency of measuring translation in clinical roentgenograms, where concomitant motion factors may be present, but not explicitly considered. Results indicated substantially lower within- and between-rater consistency estimates relative to consistencies obtained from the model, although these magnitudes were similar to those reported by others evaluating clinical roentgenograms. The implications of lower consistency estimates relative to increased false-positive and false negative rates must be more closely examined. These studies present evidence suggesting that high consistency and accuracy indices do not ensure acceptable false-positive and false-negative rates and, thus, provide empirical evidence supporting the view that using roentgenograms as a basis for diagnosing instability often can lead to errors in classification. This is less so when observed translations are relatively large (+/- 5+ mm) on roentgenograms that are relatively clear, with little obliquity, and when concomitant motions are minimal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2237625 TI - 1990 Volvo Award in experimental studies. The dependence of intervertebral disc mechanical properties on physiologic conditions. AB - In vivo creep-recovery and disc pressure measurements were performed on the lumbar spine of immature and mature swine. The creep-recovery measurements were performed using a custom materials testing apparatus designed to apply static or dynamic loads to the spine of anesthetized animals. A series of three separate experiments were performed to assess the effects of: (I) animal death, (II) graded injury to the disc anulus, and (III) respiratory mechanics on the biomechanical response of the porcine L1-L3 vertebral unit (VU). In Experiments I and II, creep rate, modulus, and viscosity parameters were computed using a three parameter solid rheological analysis of the displacement-time response recorded during the application of a 300-N load. In Experiment III, the effects of respiratory volume and frequency changes on disc pressure were assessed in the unloaded, statically loaded, and immobilized porcine VU. Our results indicated that the adult VU tended to be stiffer, deform or creep more slowly, and had a significantly higher viscosity than the VU of immature pigs. The results of Experiment I demonstrated that the biomechanical response for the VU was significantly altered by the death of the animal; the VU of the living animal (adolescent or mature) was more compliant and deformed at a faster rate than the VU of the same animal after death. Disc injury produced changes in stiffness, viscosity, and creep rate analogous to that of aging, and on the basis of the graded injuries created in this study, it appears that a small defect in the annulus is just as deleterious as removing a large section of anular material. The results of Experiment III indicated that respiration plays an important role in the normal, in vivo mechanical and nutritional behavior of the porcine VU. Altogether, these results demonstrate that, in the absence of normal physiologic conditions, one may not be able to reliably predict the mechanical response of the lumbar spine, and suggest that standards for the testing, handling, and storage of biologic tissue should be established. PMID- 2237626 TI - 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model. AB - An animal model was developed to test the hypothesis that discrete peripheral tears within the anulus lead to secondary degenerative changes in other disc components. In 21 adult sheep, a cut was made in the left anterolateral anulus of three randomly selected lumbar discs. The cut was parallel and adjacent to the inferior end-plate, and had a controlled depth of 5 mm. This left the inner third of the anulus and the nucleus pulposus intact and closely reproduced the rim Lear lesion described by Schmorl. Animals were randomly allocated to different groups in relation to the length of time interval between operation and death, varying from 1 to 18 months. At death, the lumbar spine was cut into individual joint units and each disc sectioned into six parasagittal slabs. After observation of the slabs under the dissecting microscope, two of the six slabs, the one containing the anulus lesion and a contralateral, were processed for histology. The results of this study suggest that, despite the great care taken at operation to ensure that the inner anulus was left intact, progressive failure of the inner anulus was seen in all sheep and occurred in the majority of discs between 4 and 12 months after the operation. Although the outermost anulus showed the ability to heal, the defect induced by the cut led initially to deformation and bulging of the collagen bundles, and eventually to inner extension of the tear and complete failure. These findings suggest that discrete tears of the outer anulus may have a role in the formation of concentric clefts and in accelerating the development of radiating clefts. Peripheral tears of the anulus fibrosus therefore may play an important role in the degeneration of the intervertebral joint complex. PMID- 2237627 TI - The loads on the lumbar spine during work at an assembly line. The risks for fatigue injuries of vertebral bodies. AB - This study was performed in an attempt to determine the total spinal compressive load during assembly line work to find a possible association with the many complaints of back pain. A flexion analyzer was used to register trunk movements, and analysis of postures and lifted weights was done from video recordings. The load on the spine at the L3 level was calculated through a biomechanical model, meant for analysis of static, sagittally symmetric postures and lifting tasks. Maximum lift tests were performed before and after a full work day. The peak load on the L3-L4 level when lifting corresponded to an average 22% of the load at the lift test. The mean load during a work cycle was 818 N. It was concluded that the many complaints of back pain could not be attributed to high peak loads, repetitivity of the lifts, or large load doses. Monotony, stress, and low job satisfaction are more likely factors of greater importance. PMID- 2237628 TI - Comparison of structure, mechanical properties, and functions of lumbar spinal ligaments. AB - The organization of collagen in the supraspinous, interspinous, and longitudinal ligaments, as well as the ligamenta flava, in lumbar spines from human cadavers has been investigated by polarized light microscopy, scanning electron microscopy, and x-ray diffraction. These experiments were performed on ligaments in situ, with their bony attachments undisturbed, and on excised ligaments at a range of applied strains. Results were related to the composition (investigated by standard histologic techniques) and gross structures (investigated by light microscopy) of the ligaments. More importantly, the results were related to the mechanical properties of the ligaments, which include stiffness, failure conditions, stress relaxation, and hysteresis. Where necessary, results were supplemented by or compared with those obtained from pig ligaments. Mechanical properties were related to postural changes by ligament strains induced in cadaveric specimens, using results from the literature. Thus, ligament structures could be related to their physiologic functions. PMID- 2237629 TI - Computer-assisted tomography of scoliosis operated with or without Harrington's rod. Biomechanics aspects of the fusion. AB - Forty-eight cases of posterior vertebral arthrodesis for scoliosis, performed with or without instrumentation, were examined using computed tomography (CT) scanning to study the evolving fusion mass. The authors observed that the fusion mass area is more voluminous in the cases performed without instrumentation than in the ones performed with instrumentation, and that 2 years after fusion the bone mass shows already a considerable increase. For the cases operated with Harrington's technique, the increase of the fusion mass is very slow and becomes considerable 5 years after operation. In both series, the section of the fusion masses at the apex of the curve is asymmetric (with prevalence on the concave side), with an area of central resorption that shows the structure of a long bone (box section). PMID- 2237630 TI - Factors influencing the result of posterior spinal fusion in the treatment of adolescent idiopathic scoliosis. AB - Sixty-six consecutive patients with adolescent idiopathic scoliosis treated by posterior spinal fusion using Harrington distraction compression instrumentation were followed for a minimum of 3 years. Initial surgical correction was satisfactory, but during the follow-up period, mean 4.4 years (3-5 years), there was a loss of correction. Several factors (age, sex, the number of vertebrae in the fusions, and the use of cross wires) were important influences on correction. A method of assessing the balance of a posterior spinal fusion is described that is useful when assessing radiographs. PMID- 2237631 TI - The operative treatment of progressive early onset scoliosis. A preliminary report. AB - Thirteen patients with progressive early onset scoliosis have been managed operatively in an attempt to achieve correction without bracing and to allow the spine to grow. All had posterior segmental spinal instrumentation (SSI) without fusion and 9 of 13 had anterior apical growth arrest as a separate additional procedure. At 2-year follow-up, curve correction averaged 46%. Patients who had anterior apical growth arrest and SSI without fusion had less curve deterioration than those who had SSI alone. New methods are described for 1) measuring growth of the instrumented segment of the spine and 2) calculating the predicted growth of the instrumented segment. Eight of the 13 had more than 50% of predicted growth, three had 30-50% of predicted growth, and two had less than 30% of predicted growth. Operative treatment has been successful in the short term in all but the most malignant form of infantile idiopathic scoliosis. PMID- 2237632 TI - An analysis of the effect of the Zielke operation on S-shaped curves in idiopathic scoliosis. A follow-up study revealing some skeletal and soft tissue factors involved in curve progression. AB - This article analyzes the fate of S-shaped idiopathic spinal curves during follow up in 18 patients having the Zielke VDS operation. The spinal radiographs were evaluated by Cobb angle, end-vertebra angles (EVAs), vertebral rotation, and by a new method using the tilt of the surgically fused spinal block in the frontal plane. Spinal growth was measured. Using the conventional criterion for Cobb angle progression, 83% of the lower curves and 50% of the upper curves progress. The use of EVAs shows that progression occurs mainly in the middle (thoracolumbar) segment of the spine. Curve progression occurs in the frontal plane without any significant change in vertebral rotation. The progression of the upper curve Cobb angle is not related to the progression of the Cobb angle of the lower curve; but it is related to 1) tilt of the spinal block, 2) growth of the spine below the block and 3) overall linear spinal growth (T1-S1). Progression of the upper EVA of the upper curve is associated with skeletal immaturity. The key features leading to curve progression after the Zielke operation appear to be spinal asymmetry in the frontal plane, linear spinal growth, and concave lumbar muscle tether (myostatic contracture). The surgical implications of the findings are outlined. PMID- 2237633 TI - Effects of rib elongation on the spine. I. Distortion of the vertebral alignment in the rabbit. AB - Elongation of one rib on the right side by 1 cm was achieved in two groups of adult rabbits of different age, by osteotomy and application of a metallic expander. The procedure resulted in immediate deviation of the spine in the frontal and sagittal planes, with moderate scoliosis, convex to the left, and a significant decrease in the normal cervicothoracic lordosis and thoracolumbar kyphosis. Moreover, computed tomography (CT) scanning demonstrated rotation of vertebra about the longitudinal axis relative to the anterior midline of the body, and deviation of the spinous process toward the convex, left side, of the scoliotic deformity. Rib hump developed on the right side--that of the elongated rib. These changes, which occurred simultaneously in the three planes, were less pronounced in the group of older animals. Two weeks after the operation, the distorted configuration of the spine remained unchanged. The observed changes in the alignment of the vertebrae--changes that, except for their direction on the horizontal plane, resembled those associated with idiopathic scoliosis in man- support the earlier proposed link between the early stage of development of this condition and asymmetry of rib growth. PMID- 2237634 TI - Effects of rib elongation on the spine. II. Correction of scoliosis in the rabbit. AB - Three intercostal nerves on the right side of growing rabbits were resected partially. From 1 to 3 months later, moderate left-convex thoracic scoliosis with rotation of vertebrae had developed, and the sagittal curvatures of the spine had diminished. In one group of these animals, a mechanically produced increase of 1 cm in the length of one rib on the side of the convexity resulted in an immediate correction of the scoliotic deformity, an improvement that was still evident 3 weeks after the operation. In two other groups of rabbits, a further resection of three intercostal nerves, this time on the left convex side, 1 and 2 months after the first operation, resulted in regression of scoliosis or halted its progression. These results further support a new concept in which the precipitating factor in the development of scoliosis is ascribed to asymmetric longitudinal growth of the ribs. They also suggest that regulation of the rib length could be a promising approach to the effective correction of progressive scoliosis at an early stage in man. PMID- 2237635 TI - Maintenance of cell viability in stored bone. AB - Although stored autogenous bone is routinely used for bone grafting in spinal surgery, the cellular elements of this bone do not survive the period of storage under standard conditions. By the use of tissue culture techniques, the authors show that it is possible to keep bone cells alive for many weeks. The potential advantages of maintaining cellular viability in grafted bone is discussed. PMID- 2237636 TI - A variant of severe deformation of the thoracic spine with favorable neurologic outcome. PMID- 2237638 TI - Monochromosomal mouse microcell hybrids containing inserted selectable neo genes. AB - Normal mouse fibroblasts at early passage levels were used as a starting material to construct mouse-hamster microcell hybrids (MCH). The neor gene, carried on the pSV2neo and pZIP-NeoSV(X)1 plasmids, was introduced into the mouse fibroblasts by gene transfection and retroviral infection, respectively, prior to microcell hybridization into the E36 Chinese hamster cell line. In total about 180 MCH clones were isolated and their amount of mouse DNA was estimated by dot-blot analysis. About 50% of the transfection based hybrids (T-hybrids) showed signals indicating one mouse chromosome, less than 10% more than one mouse chromosome, and the remaining clones contained only subchromosomal amounts of mouse DNA. In the infection-based hybrid series (I-hybrids) more than 95% showed only subchromosomal mouse DNA content. Chromosomal integration analysis verified the presence of neor insertions in all 42 hybrid clones analyzed. C-banding analysis verified 14 of 15 hybrids scored as monochromosomals on dot blots. Chromosome fragmentation in T-type MCH was found to be (1) nonrandom, preferentially occurring in MCH derived from certain transfectants, (2) late in clonal establishment, and (3) essentially not related to prolonged cultivation in vitro. Once established, most T-type MCH clones including mono- and subchromosomal hybrids were essentially stable during prolonged cultivation. In contrast MCH initially containing several mouse chromosomes tend to lose the nonselectable ones during prolonged cultivation. In total we estimate the number of independent monochromosomal MCH derived in this study to more than 30. PMID- 2237637 TI - Giant-cell tumor involving a lumbar vertebra. Long-term follow-up after radiotherapy. PMID- 2237639 TI - Targeted gene replacement at the endogenous APRT locus in CHO cells. AB - We demonstrate the feasibility of targeted gene replacement at an endogenous, chromosomal gene locus in cultured mammalian cells, employing a two-step strategy similar to an approach routinely used for genetic manipulation in yeast. Utilizing an APRT+ recombinant generated by targeted integration of plasmid sequences (including a functional copy of the gpt gene) at the CHO APRT locus, we have been able to select gpt- "pop-out" recombinants that have arisen by intrachromosomal recombination between APRT direct repeats at the targeted integration site. Reciprocal exchanges leading to "pop-out" of integrated plasmid/gpt gene sequences occur at a rate of approximately 6.3 x 10(-6) per cell generation. Depending on the site of crossover, such "pop-out" events result in either replacement or restoration of the original APRT target gene sequence. PMID- 2237640 TI - Isolation of temperature-sensitive CHO-K1 cell mutants exhibiting chromosomal instability and reduced DNA synthesis at nonpermissive temperature. AB - Twenty-five temperature-sensitive (ts) mutants were isolated from Chinese hamster CHO-K1 cells after mutagenization with N-methyl-N'-nitro-N-nitrosoguanidine. Of 13 complementation groups identified, nine exhibited chromosomal instability at a nonpermissive temperature. They were classified into three major classes according to inducibility of sister chromatid exchange (SCE) and/or chromosomal aberration (CA): class 1 resulted in predominant SCEs, class 2 manifested both SCEs and CAs, and class 3 exhibited higher induction of CAs. Flow cytometric analysis of the mutants exhibiting chromosomal instability indicated that many of the mutants were arrested in the S or S to G2 phases of the cell cycle at the nonpermissive temperature, accompanied by a decrease in the rate of DNA synthesis. These results imply that ts defects are related to some points in DNA replication and might be responsible for the induction of SCEs and/or CAs at the nonpermissive temperature. PMID- 2237641 TI - Replication-dependent mutagenesis by 5-bromodeoxyuridine: identification of base change and sequence effects on mutability. AB - The molecular mechanism of reversion induced by 5-bromodeoxyuridine (BrdU) replication-dependent mutagenesis in mammalian cells was studied. Murine cells with single mutant copies of the E. coli gpt gene integrated chromosomally as part of a shuttle vector were mutagenized with BrdU, and GPT+ revertants were selected. Thirteen mutant cell lines (each of which had a gpt gene that varied from the wild-type gene by a different GC----AT base transition in the coding region) were mutagenized, and only four were found to be effectively reverted. All revertant gpt genes that were analyzed had reverted via AT----GC base transition at the original site of mutation, thus demonstrating that replication dependent mutagenesis by BrdU causes AT----GC transitions. The nine cell lines that were nonrevertible by BrdU replication-dependent mutagenesis could be mutated by this protocol to ouabain resistance as effectively as the four revertible lines, indicating that the nonrevertible lines were susceptible to such mutagenesis. Thus, differences among the cell lines in frequencies of HATr revertants generated by BrdU replication-dependent mutagenesis could not be attributed to differences in general susceptibility of the lines to the mutagenic protocol. The revertible and nonrevertible lines could not be separated according to the position of the original GC----AT transition in the gpt coding region. However, there was evidence that the DNA base sequence flanking the site of mutation affected the susceptibility of that site to BrdU replication-dependent mutagenesis. For example, six of the cell lines tested had gpt genes in which the mutant T residue was immediately adjacent on its 3' side to an A residue, and all six were found to be nonrevertible by BrdU replication-dependent mutagenesis. Furthermore, a target AT base pair flanked by GC base pairs in opposite orientation and either immediately adjacent to or one base removed from the target site on both the 5' and 3' sides appeared to have an increased susceptibility to BrdU replication-dependent mutagenesis. PMID- 2237642 TI - Genes for C4b-binding protein alpha- and beta-chains (C4BPA and C4BPB) are located on chromosome 1, band 1q32, in humans and on chromosome 13 in rats. AB - C4b-binding protein is involved in the regulation of the complement system. It is a multimeric protein composed of seven identical alpha-chains and a single copy of a unique beta-chain. The latter was identified only recently and its structure determined by cDNA cloning. Both subunits in C4b-binding protein belong to the same superfamily of proteins composed predominantly of tandemly arranged short consensus repeats (SCR) approximately 60 amino acid residues in length. The gene for the human alpha-chain is known to be located in a gene cluster on chromosome 1, band 1q32, which is called the regulators of complement activation (RCA) gene cluster. We have used cDNA probes for both alpha- and beta-chains of human C4b binding protein to localize their genes with an in situ hybridization technique. We find the genes for both chains to be located on chromosome 1, band 1q32, in the human. This suggests that the beta-chain gene is also a member of the RCA gene cluster and that the alpha- and beta-chain genes are located close to each other. The cDNA probes for the alpha- and beta-chains also were used to screen mouse-rat somatic cell hybrids using Southern blotting to localize their genes in the rat. Both the alpha- and beta-chain genes were shown to be located on chromosome 13 in the rat. These are the second and third genes to be located on rat chromosome 13, and the results suggest that the genes for the alpha- and beta chains together with the gene for coagulation factor V represent a conserved chromosomal region in rat and man. PMID- 2237643 TI - [Current radiologic diagnosis of esophageal tumors]. PMID- 2237644 TI - [Spiral-CT: a new technique for volumetric scans. I. Basic principles and methodology]. PMID- 2237645 TI - [Vascular embolization for the treatment of life-threatening hemorrhages in the pelvic area]. PMID- 2237646 TI - [An atypical radiologic finding in a case of Pneumocystis carinii pneumonia]. PMID- 2237647 TI - [Merkel cell carcinoma: differential diagnosis and appropriate therapy]. PMID- 2237648 TI - [Problems of hemorrhage in the cerebellum]. AB - The authors give an account on their experience with the treatment of five patients (three women and two men) with non-traumatic haemorrhage into the cerebellum. The oldest patient was 67 years, the youngest 14 years, the mean age was 51.2 years. In four the cause of haemorrhage was hypertension, in one patient an A-V malformation. The correct diagnosis was established by CT examination, while originally it was assumed that a supratentorial cerebrovascular attack was involved. One female patient recovered after conservative treatment, in the remainder the haematoma was removed by suboccipital craniectomy. One patient died, the fourteen-year-old female patient which was admitted with symptoms of decerebration, survives with a marked neurological deficit, three patients feel well. In one instance hydrocephalus developed which was treated by ventriculo peritoneal drainage with a valve. PMID- 2237649 TI - [Epidural hematomas in the posterior cranial fossa]. AB - In the course of twenty years 92 patients with intracranial epidural haematomas (EH) were operated. In five these patients, i.e. 5.4%, the EH was in the posterior cranial fossa (EHPF). Focal symptoms of compression of the cerebellum and the lower cranial nerves developed only in subacute EHPF. In acute EHPF it was masked by manifestations of an affection of the brain stem. Direct evidence of EHPF was produced by AG. The best diagnostic method is computed tomography. Attention to EHPF can be however, drawn also clinical sings of injury of the bask of the skull or the finding of a fracture of the occipital bone on an X-ray picture of the skull. Evacuation of the EHPF provides favourable perspectives of a normal future life even on patients who are in a poor condition incl. signs of and impaired respiration. PMID- 2237650 TI - [Prevention of pulmonary embolism after brain surgery with the use of local heparinization]. AB - The authors describe briefly anticoagulation treatment of thrombosis of the lower extremity by heparin which developed on the third day after operation of a glioblastoma of the temporal lobe. An adequate therapeutic dose of heparin administered by infusion into the affected lower extremity was neutralized by an infusion of protamine into the upper extremity. Haematological examination revealed normal clotting in the systemic circulation. The method of local heparinization improved the clinical symptoms, pulmonary embolism did not develop and was there was no hemorrhage complication in the surgical field. PMID- 2237651 TI - [Intracranial hemorrhage as a complication of anticoagulation therapy]. AB - The authors describe two cases of intracranial haemorrhage as a complication of anticoagulation treatment, and compare their results with those reported in the literature. They analyze risk factors which in conjunction with anticoagulants chuan lead to haemorrhage. PMID- 2237652 TI - [Instruments used in various operations in the area of the gasserian ganglion]. AB - The authors describe instruments which make it possible to perform retrogasserian thermolesions (RGT), glycerol radiculolysis (GRL) or trigeminal balloon compression (TBC) or possibly a combination of these methods from a single surgical approach. This makes it possible to adjust the selection of the type of lesion to unforeseen conditions any time during the operation. The surgical results are compared in 308 RGT, 50 GRL and 22 TBC. There are no substantial differences and therefore the selection of the type of lesion depends on technical circumstances during operation. PMID- 2237653 TI - [Diagnosis of traumatic ruptures of the bronchi]. AB - The author presents a report on the course of the disease and diagnostic difficulties of a rupture of the bronchus in a patient with a severe thoracic injury. He draws attention to the diagnostic difficulties in these injuries and evaluates diagnostic and therapeutic possibilities. She assumes that with more frequent chest injuries the possible more frequent incidence of these injuries must be foreseen. The author emphasizes interdisciplinary team work in the diagnosis of the condition and the comprehensive character of care. PMID- 2237654 TI - [Bacteriological findings in bronchial secretions of the lower respiratory tract in resected lungs]. AB - The authors investigated during operation the bacteriological findings in the bronchial secretion of the respiratory pathways of resected lungs. Of 100 patients whom they included in the group they detected a positive finding in 42. Wound in 27 patients. Twenty of them had a positive bacteriological finding in the lower respiratory pathways. The authors discuss the problem of prophylactic use of antibiotics in pulmonary surgery. Based on data in the literature and their own observations, the authors recommend preventive administration of antibiotics in pulmonary surgery. PMID- 2237655 TI - [Functional treatment of calcaneal fractures]. AB - The authors discuss functional treatment of fractures of the calcaneus. They compare the therapeutic results of the most serious type of these fractures- intraarticular compressive fractures with depression of Bohler's angle, treated in the classical manner by long-term plaster and by the modern method--functional treatment which involves a minimal period of immobilization--general and local- and makes early and intensive rehabilitation possible very soon after the injury. The functional method gives very good results and reduces the period of treatment. By reducing the period of work incapacity it is an asset for the national economy. PMID- 2237656 TI - [False aneurysm of the anterior tibial artery as a sequela of complicated foreleg fracture]. AB - The authors discuss the aetiology, diagnosis and therapy of false aneurysms and mention their possible occurrence at different sites, whereby they emphasize the rare occurrence of pseudoaneurysms in conjunction with fractures of the bones of the extremities. The rare nature of the mentioned complication stimulated the authors to present a case-history of a pseudoaneurysm of the anterior tibial artery. PMID- 2237657 TI - [Pitfalls and complications of the Weidner-Ender method of osteosynthesis in the treatment of fractures of the proximal part of the femur]. AB - Ender's method is associated not only with advantages but also with some pitfalls and risks. The advantages--adequate stability, small surgical stress, small blood losses during operation, minimal risk of infection. Complications during operation, during the postoperative period and during subsequent by evaluation of the general condition of the patient and the type of fracture, by perfect reposition, correct surgical procedure--selection of a trepanation aperture, correct length of wires, adequate number of wires, early mobilization and gradual bordening of the operated extremity during walking. The authors present a group of 174 operated patients, incl. 159 where Ender's method of osteosynthesis was applied: in a total of 18 basicervical, 148 pretrochanteric and 8 subtrochanteric fractures. Complications developed in 11 patients--8 times distal dislocation of the wires, 6 times various dislocations of the fragments, 7 patients died after operation. PMID- 2237658 TI - [Replantation of traumatically amputated parts of extremities-- indications and nomenclature]. AB - The authors submit a brief report on replantation activities during the past five years and discuss the problem of indications and terminology of traumatic amputations. The paper contains instruction regarding communication by telephone between the attending surgeon and a specialized microsurgical department. There are also instruction how to handle the amputated portion of the limb and how to transport the patient and the amputated portion of the limb. The authors discusses traditional procedures in replantation surgery on the basis of his own experience with 292 replantations or revascularizations. PMID- 2237659 TI - [Professional profiles of physicians]. PMID- 2237660 TI - [Evaluation of emergency surgical procedures and their tolerance by the patient]. PMID- 2237661 TI - [Use of a scoring system for categorizing polytrauma and polytraumatism]. PMID- 2237662 TI - [Emergency conditions and surgery in Czechoslovakia]. AB - Urgent surgical operations account for cca 28% of all surgical activities in Czechoslovakia. Their lethality is by cca one third higher than in other operations. The period of treatment is, however, shorter, no doubt, because before operation there is not time for complicated examinations. A great proportion of urgent operations is formed by acute abdomen, cca 60%. So far even prolonged efforts did not succeed to achieve earlier hospital admission. The operations are, however, made at an earlier stage and thus the lethality declined. As to age, a great proportion of urgent conditions occur in older children and adolescents, old patients above 65 years and in particular above 75 years. Men are affected more frequently. Interregional comparisons indicate a varied incidence but in particular a varied lethality. It is high specially in Prague and the South Bohemian region although the two regions have a relatively low relation of incidence. In the conclusion the authors emphasize that it is important to make an effort to improve care of urgent patients by health education and by convincing doctors of the importance of the time factor. PMID- 2237663 TI - [The professional profile of level I and II certified urologists]. PMID- 2237664 TI - [The role of ultrasonographic examination in the diagnosis of thyroid gland disorders]. AB - The authors compared the results of ultrasonographic examinations of thyroid processes with clinical and histological findings of operated patients. The results proved the importance of ultrasonographic examinations as one in the complex of examination methods before operation of the thyroid gland for the assessment of the preoperative diagnosis. PMID- 2237665 TI - [Supravalvular aortic stenosis]. AB - The authors describe the case of an inborn supravalvular aortal stenosis in an adult patient who was successfully treated by a plastic operation of the stenotic portion of the ascendent aorta by means of a synthetic patch. At the same time also a plastic operation of an incompetent mitral valve was made. PMID- 2237666 TI - [Do we amputate too much or too little? A retrospective analysis of the situation in the East Bohemian Region]. AB - A retrospective analysis of 1146 amputations of the lower extremities in five departments of the East Bohemin a region revealed that the number of amputations in the thigh is higher and less frequently preceded by angiographic examination and reconstruction operations of the arteries as compared with distinguished departments abroad. The mortality after amputations was 12.5%. The results call for more intensive training of vascular surgeons and the establishment of vascular surgical departments where it would be possible by early reconstruction operations made in time to prevent amputations or at least shift the height of the amputation in the most distal direction possible. PMID- 2237667 TI - [Diagnostic and therapeutic problems in carcinoma of the esophagus and cardia]. AB - The authors describe their experience with the treatment of 180 patients with tumours of the oesophagus and cardia, during a 13-year period, at the Surgical Clinic, Medical Faculty, Comenius University, Bratislava. Most frequently the tumorous process was in the median portion of the oesophagus. A radical operation could be performed only in 27.2% of patients. The reason was that frequently the tumours were already very advanced when the patients were admitted to the surgical department; that means: late diagnosis. This explains also the short postoperative survival. The authors analyze the reasons for the above described facts and submit their concept of the diagnostic and therapeutic approach to the problem of carcinoma of the oesophagus and cardia. PMID- 2237668 TI - [Personal experience with liver injuries]. AB - The authors give an account of 69 patients hospitalized in 1975-1986 in the Traumatological Research Institute in Brno on account of liver injuries. The mean age of the patients was 38.3 years. The liver injury was very frequently associated with serious craniocerebral injuries, with injuries of the chest and other intraabdominal organs and the total lethality was 62.3%. The most frequent cause were traffic injuries (50 cases). Blunt liver injuries accounted for 92.8% of the cases. PMID- 2237669 TI - [Postcholecystectomy syndromes]. AB - The author analyzes postcholecystectomic complaints in 513 patients cholecystectomized in 1981-1985. He mentions the relationship between postcholecystectomic syndromes and preoperative complaints, the peroperative diagnosis and surgical operation. He recommends diagnostic investigations to elucidate the dyspepsia; the doctor must not be satisfied with the finding of cholecystolithiasis. The author also compares postcholecystectomic syndromes in patients with a biliodigestive anastomosis with papillosphincterotomy. The author analyzes in more detail the experience with treatment of nine patients, i.e. 1.75% patients with the finding of residual concrements. PMID- 2237671 TI - [Necrotizing pancreatitis and its complications managed by surgery]. AB - The authors have summed up their 10-years experiences (1978-1987) with the therapy of acute necrotizing pancreatitis and of some serious surgical complications. While in 252 patients operated early for biliary pancreatitis mortality rate did not exceed 8.7% in 65 patients operated for necrotizing abscessing pancreatitis and its complication it was as many as 63%. The stress has been laid both on early operations of biliary tract diseases and the prevention of developing severe forms of pancreatitis. Even in the cases of advanced necrotizing pancreatitis, priority has been given to radical necrectomy as early as in the second week of the disease duration supplemented with lavage and profuse drainage. The maintenance of therapeutical laparostomy is suitable. PMID- 2237670 TI - [Treatment of liver rupture in an experiment]. AB - The authors investigated in experiments on rabbits healing of liver incisions under various circumstances: spontaneous healing, liver incisions treated by suture by application of the tissue glue Tissucol, the collagenous haemostatic felt Collastypt combined with one stitch. Healing was followed up after several time intervals. From normal, i.e. the group of spontaneous healing, differed the groups treated by Tissucol and Collastypt where marked encapsulating fibrous tissue reactions round the necroses on the wound margins were found with numerous eosinophils as a transient phenomenon. The final result (with a maximum of cca two months) was adequate in all groups--as a rule a thin fibrous tissue scar with few remnants of atrophic hepatic trabeculae. In the treatment of small injuries it seems best to use the collagenous haemostatic Collastypt. In the treatment of sutures in rare instances a large number of leucocytes was found in the area of the necrosis and stitches, perhaps as result of contamination of the wound or sewing material. PMID- 2237673 TI - [Methylprednisolone-pulse therapy in a patient with rheumatoid arthritis and diffuse interstitial pneumonia/pulmonary fibrosis]. AB - A forty-eight year-old female with rheumatoid arthritis developed cough, sputum and dyspnea. Chest X-ray film demonstrated bilateral diffuse interstitial pneumonia and pulmonary fibrosis. Laboratory findings were as follows: ESR 29 mm/h, CRP 3.86 mg/dl, RA test (+), RAHA (-) and WBC 7200/mm3. Marked hypoxemia (po(2)45 Torr) was demonstrated by blood gas analysis. Asymptomatic pulmonary fibrotic lesions which preceded articular symptoms were identified on her previous chest X-ray films. Methylprednisolone-pulse therapy (1g/day, for 3 days) was repeated three times with a 2-week interval. The treatment rapidly improved both pulmonary symptoms and chest X-ray findings. Although the fibrotic shadows on chest X-ray did not completely disappear, her conditions have been maintained well under the treatment with prednisolone (10mg/day) plus D-penicillamine (200mg/day). PMID- 2237672 TI - [Quantitation of intact form of complement protein B and its fragment Ba in human serum by radioimmunoassay]. AB - A sensitive solid-phase radioimmunoassay for intact complement protein B and its smaller fragment Ba is described which quantitates human B and Ba to 30 ng/ml. The assay was proved to be useful to evaluate the activation of the alternative pathway of the complement system by measuring intact B and Ba in normal human sera activated with zymosan. In sera from patients with systemic lupus erythematosus (SLE), the level of intact B was decreased and that of Ba was increased in the active phase, and the level of Ba was increased though intact B which was within normal limits in the inactive phase. The present result suggests that the activation of the alternative pathway is occurring both in the active and inactive phase in SLE, and the measurement of intact B and Ba concentration in pathological sera would be useful to evaluate the activation of the alternative complement pathway. PMID- 2237675 TI - [A retrospection of long-time research on fibrinoid, and its further problems]. PMID- 2237674 TI - [Protein kinases in signalling of T-cell growth]. PMID- 2237676 TI - [Intra-articular rheumatoid nodules of the knee joint]. AB - Intra-articular rheumatoid nodules found in 6 knee joints of 4 patients with rheumatoid arthritis were reported with histological findings. All patients were women, ranging in age from 32 to 61 years, with 6 to 41-year history of rheumatoid arthritis. The masses were exclusively in the anterolateral aspect of the joint. Snapping occurred when the joint was flexed by 20 degrees in four joints and by 60 degrees in two. The masses had the sizes of a thumb tip to index finger tip, and were elastic and soft. Histologic examination of the masses revealed the typical formation of rheumatoid nodule in two joints. Myxomatous degeneration and granulation tissue consistent with rheumatoid arthritis were found in two joints. Perivascular fibrosis and myxomatous degeneration were mainly demonstrated in two joints which had developed masses two months before excision. PMID- 2237677 TI - [Clinical studies on 9 patients with Heberden's nodes of premenopausal onset]. AB - Nine patients with Heberden's nodes of premenopausal onset were studied for complications in the form of thyroid disorders as well as from the hereditary, roentgenological and immunological aspects. In addition, rheumatoid arthritis, psoriatic arthritis, traumatic arthritis, erosive osteoarthritis or adult Still's disease was excluded in these patients. All patients had thyroid disorder (Basedow's disease in 6 patients, Hashimoto's thyroiditis in 2 patients and granular thyroiditis in one patient). Immunological examinations were positive for anti-thyroglobulin antibody in 5 patients and anti-microsome antibody in 3 patients and anti-nuclear antibody in 2 patients. Roentgenological findings revealed no typical signs of primary generalized osteoarthritis. PMID- 2237678 TI - 5-HT--crossing a new frontier. PMID- 2237679 TI - Towards safer anaesthesia--implementing practice standards. PMID- 2237680 TI - Doomsday forecasts of the AIDS epidemic. PMID- 2237681 TI - Our daily bread--is it threatened? PMID- 2237682 TI - On the maximum size of the AIDS epidemic among the heterosexual black population in South Africa. AB - Using a macro-simulation model, the maximum size of the acquired immunodeficiency syndrome (AIDS) epidemic among the heterosexual black population of South Africa is assessed. As a result of the simulations, it appears very unlikely that the demographic impact of AIDS is such that the size of the black population will be substantially reduced during the next three decades. A realistic 'worst-case' scenario is that population growth will come to a halt on a population level substantially higher than the present one. It is also unlikely that peak infection levels among the sexually active population will exceed 30-40%. However, especially in urban populations, it cannot be ruled out at present that infection levels of 30% will be reached within the next 10-15 years. PMID- 2237683 TI - Knowledge, attitudes and beliefs about AIDS in township school students in Cape Town. AB - Students (N = 377) from four Cape Town township high schools were surveyed to obtain information on their knowledge of and attitudes towards the acquired immunodeficiency syndrome (AIDS), and on their sexual behaviour. The study was undertaken to provide information for planning an AIDS education intervention. Three-quarters of students reported that they had had sexual intercourse. Most students had heard of AIDS, and the majority of these knew that it was infectious. More than half of the students were confused or lacked knowledge about the modes of transmission. Two-thirds of the students believed AIDS could be prevented, but knowledge of prevention strategies was superficial. Of the sexually active students only 11.4% had ever used a condom, and of all students 39.6% stated that they would use a condom in the future. Two-thirds of the students were not aware that there is no cure for AIDS. Students did not acknowledge that AIDS could affect them directly, and attributed the problem to prostitutes and 'promiscuous' people in 36.4% of responses, and to 'white' people in 23.8% of responses. Students expressed intolerance, fear and rejection of people with AIDS, and only 6.4% would accept an affected person into their class. Almost all the students wanted AIDS education at school, and most of these requested that the school nurse facilitate this education. It is concluded that appropriate AIDS prevention education is urgently required for both high school and junior school students. PMID- 2237684 TI - Knowledge, beliefs and practices among black goldminers relating to the transmission of human immunodeficiency virus and other sexually transmitted diseases. AB - The Chamber of Mines of South Africa employs approximately 750,000 miners from all over southern Africa. Sero-surveys in 1986 showed that, depending on geographical area of origin, between 0.02% and 3.76% of miners were positive for human immunodeficiency virus (HIV) antibodies. As a consequence, an intensive education campaign to stop the spread of HIV infection was launched. A study was undertaken to establish a valid baseline level of knowledge about black miners' beliefs, attitudes and practices related to HIV infection, acquired immunodeficiency syndrome (AIDS) and sexually transmitted diseases (STDs), and to recommend appropriate changes to the educational efforts of the Chamber of Mines. A structured, pre-tested questionnaire was used to interview in their home language 429 systematically sampled black miners from four different mines. The most relevant findings were that younger age, not being married and how general education predispose to contracting STDs, while a feeling of being at risk for contracting HIV infection is positively correlated with level of education. Close friends were the most important source of information on STDs, but the media and medical staff were the most important sources of information on AIDS/HIV infection. Condoms were used by 31% of respondents, while the main reasons for non-use were trust in the sexual partner and lack of availability. Promotion of a stable family life for miners may significantly impact on the transmission of HIV infection. PMID- 2237685 TI - Some early observations on HIV infection in children at King Edward VIII Hospital, Durban. AB - Nine black children aged between 3 months and 30 months of age, with human immunodeficiency virus type I (HIV-I) infection are described to draw the attention of health professionals in southern Africa to special clinical characteristics useful for recognising this problem, which has many shared features with common diseases of infancy and childhood in the Third World. The main presenting complaints were chronic cough and persistent diarrhoea and vomiting. These children frequently had diarrhoea (8 of 9 patients), mucocutaneous candidiasis (8), pneumonia (7), hepatosplenomegaly (9), significant lymphadenopathy (5) and wasting (5). All were infected by common bacteria, such as Gram-negative organisms, Mycobacterium tuberculosis and Campylobacter jejuni, or by opportunistic infections such as Candida or cytomegalovirus (CMV), or by both bacterial and opportunistic organisms. A raised total serum globulin level, anaemia, lymphopenia and a cerebrospinal fluid (CSF) pleocytosis were frequent findings. Incomplete data on parental HIV status suggest perinatal transmission. Three of the children were HIV-antigen positive. The diagnosis of full-blown acquired immunodeficiency syndrome (AIDS), using the stringent Centers for Disease Control criteria, is difficult in our situation because of limited diagnostic resources; however, using these criteria, and the clinical case definition for AIDS recommended by World Health Organisation, it is thought that probably 4 of these children could be considered as having AIDS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237686 TI - Human immunodeficiency virus infection in children--prevalence and psychosocial impact. AB - As at 20 September 1989, 15 children with the acquired immunodeficiency syndrome (AIDS) had been diagnosed in South Africa and indications are that this number is going to increase at a rapid rate in the near future as the disease establishes itself in the heterosexual population. A brief overview of the clinical aspects of human immunodeficiency virus infections in children is given before the psychosocial implications are considered in more detail. PMID- 2237687 TI - AIDS and tuberculosis. AB - The diagnostic and therapeutic implications of human immunodeficiency virus (HIV) infection and tuberculosis in South Africa, where tuberculosis remains a major health problem, are reviewed. Mycobacterium tuberculosis is a high-grade pathogen and is able to establish infection early in immunodeficiency. With HIV infection showing significant entry into the heterosexual population in the RSA, an increasing number of cases with both infections can be expected to occur. The radiological appearance in combined infection is variable, ranging from a formal cavitatory picture to the more common finding of diffuse pulmonary infiltration. Intrathoracic adenopathy is a more specific sign of tuberculosis in HIV infection, since it is not associated with persistent generalised lymphadenopathy and pulmonary opportunistic infections, such as Pneumocystis carinii pneumonia. Intercurrent pneumonic infections and other pulmonary manifestations of HIV disease render the interpretation of new infiltrates on chest radiography problematical. Tuberculin skin testing remains useful in HIV infection and should be performed in all HIV-infected patients. The value of tuberculosis serology still remains questionable. Standard antituberculosis drug regimens are effective, but maintenance treatment must be continued for life and should include isoniazid and rifampicin. BCG vaccination is recommended routinely at birth in infants with HIV infection and for asymptomatic HIV-infected individuals who have not previously been immunised. PMID- 2237688 TI - Electro-encephalography and performance in a poorly nourished South African population. AB - The electro-encephalographic (EEG) characteristics and psychometric performance of 'normal' black South African peri-urban children were assessed in the course of a large-scale normative study. Children identified as being poorly nourished according to growth standards were compared with a group of mildly growth retarded children and with another group with normal growth. The socio-economic backgrounds of the three groups were checked and found to be the same. The children had had access to regular clinic attendance and none had ever been hospitalised for any serious illness--in particular malnutrition. Across the entire age range the poorly nourished children invariably were found to fare worse on both EEG and psychometric measures than the normal group. PMID- 2237689 TI - Electro-encephalographic disturbances due to chronic toxin abuse in young people, with special reference to glue-sniffing. AB - A study was carried out in order to document any abnormalities in the electro encephalogram (EEG) that might appear in young adolescents who have deliberately inhaled the range of volatile substances loosely referred to as 'glue'. The EEGs of a group of 'street children' being assisted in a Johannesburg shelter were examined. The records were analysed for any clinical abnormalities and also subjected to spectral analysis in order to examine the overall characteristics of frequency, power and spatial distribution. The EEGs clearly revealed that, although at the time of the examination the subjects were ostensibly abstinent, both clinical and normative evidence of continuing brain disturbance was present. It was concluded that glue sniffing is likely to have long term electrocerebral sequelae. PMID- 2237690 TI - Primary thyroid lymphomas. A clinicopathological study of 8 cases. AB - Eight elderly women with primary non-Hodgkin's lymphoma were treated with a combination of surgery, chemotherapy and radiation with excellent outcome. Clinically, the patients presented with thyromegaly and did not have lymphadenopathy or hepatosplenomegaly. On histological examination, the lymphomas resembled diffuse follicle-centre cell tumours. All patients showed extension beyond the thyroid capsule and lympho-epithelial lesions; 3 displayed kappa-light chain restriction and 2 lambda-monoclonality. Thyroid lymphomas fall into the spectrum of mucosa-associated lymphomas, which have a better prognosis than their equivalent nodal-based counterparts. PMID- 2237691 TI - Prophylaxis after needlestick injuries. PMID- 2237692 TI - Caesarean section rates in the private and public sectors. PMID- 2237693 TI - Death from septicaemia as a consequence of unwanted pregnancy. PMID- 2237695 TI - Unsuccessful sterilisation of woman--doctor liable for child-raising costs. PMID- 2237694 TI - The vitamin D status of South African women living in old-age homes. PMID- 2237697 TI - Worksite health promotion. PMID- 2237696 TI - An organizational perspective on worksite health promotion. AB - Worksite disease prevention and health promotion have developed into a field of endeavor that is accepted by a majority of employers in the United States and welcomed by many of their employees. This chapter examines the evolution of worksite health promotion and describes current worksite activities and their benefits. The authors also discuss several issues that must be addressed for the future. PMID- 2237698 TI - Debunking the myth of individual health promotion. AB - The myth is that individual health promotion programs work. The reality is that they only work in healthy organizations. An individual health promotion program is one that focuses exclusively on employee behavior change independent of the context in which the person is expected to change. This context could include the environment, the corporate culture, or the health promotion program by itself. In this chapter the author describes how individual health promotion can be enhanced through organizational health promotion and environmental modification. PMID- 2237699 TI - Meeting the health promotion challenge through a model of shared responsibility. AB - AT&T's Total Life Concept (TLC) program has incorporated a multidimensional strategy for health promotion that attempts to avoid the pitfalls of a unifocal individual approach. Combining individual, organizational, and environmental health promotion efforts, TLC has adopted an "ecological" model, which is described in this chapter. The central philosophy that unifies these three dimensions is a "shared responsibility" for health care. PMID- 2237700 TI - Reducing the risk of cancer through worksite intervention. AB - This chapter examines existing activities reported in the literature in the areas of smoking, nutrition, and screening; explores the prominent theories of behavior change that have guided some of these activities; and presents a model for worksite cancer prevention programs that is currently being tested in a large trial. A major theme of this chapter is the need for simultaneous changes in individual behaviors and the worksite environment. For each factor (smoking, nutrition, and screening) the discussion is divided into interventions for individuals and those for the environment or organization. PMID- 2237701 TI - Preventing substance abuse as an integral part of worksite health promotion. AB - Problems of substance abuse damage the well-being of many workers and drain substantial resources from the organization. While companies have adopted drug testing to screen out drug users and employee assistance programs to provide services to troubled workers, serious substance abuse prevention strategies have been virtually ignored. The authors describe some of the obstacles to implementing substance abuse programs. Attempts to integrate these programs into worksite health promotion are described and a model for a health-oriented substance abuse program is presented. PMID- 2237702 TI - Promoting mental health at the workplace: the prevention side of stress management. AB - Stress in the workplace is now widely recognized as a major problem facing American industry. A growing number of companies are offering some form of stress management intervention. However, for those seeking to introduce stress management activities, too little in the way of guidance and direction has been available. This chapter aims to help organizations better understand the sources and dynamics of stress at the worksite and examines how they can reasonably assess, implement, and evaluate their stress management options. PMID- 2237703 TI - Development of the AT&T Health Audit for measuring organizational health. AB - Like any behavioral intervention, health promotion programs require a thorough initial assessment of an array of individual and organizational problems, needs, interests, and resources. Accurate risk assessment should include both contextual and personal characteristics as well as the interaction between the two. This article describes the AT&T Health Audit, a survey that addresses worksite health issues and collects data on the prevalence of lifestyle risk factors, as well as the attitudes, knowledge, and skills related to health. A copy of the Health Audit is provided and its applications are discussed. PMID- 2237704 TI - Employer-sponsored health promotion: why and how to make it a family affair. AB - The inclusion of family members in employer-sponsored health promotion activities is an area gaining attention. Several investigations into the state-of-the-art of employer-sponsored health promotion programs for family members have been undertaken. This chapter describes the findings of the Washington Business Group on Health project. The costs and benefits of family-related health care are discussed. The authors also outline a number of ways for companies to recruit family members. PMID- 2237705 TI - Ethnic/racial populations and worksite health promotion. AB - This chapter describes the health characteristics and health risks of ethnic racial populations and the implications for planning and delivering health promotion programs at the worksite. Special consideration is given to occupational stratification, which separates these groups from their white counterparts, thus requiring special attention. Guidelines are given for designing culturally appropriate worksite health promotion programs. PMID- 2237706 TI - Aging in the 1990s and beyond. AB - The future of aging persons in an aging society will depend equally upon the exogenous factors of the society and upon our attitudes and behaviors. The changes in the numbers and proportions of elderly create constraints and pressures upon resources and services. These incentives for decision-making are then mirrored in our behaviors and attitudes about aging, and about the elderly. The role of the aging person is undergoing re-evaluation--from "retired," "grandparent," and "being seen and not heard" in family matters, to a more active and participative role. Retirement to (rather than from) second careers, political participation, community leadership, and new creativity in the choices of leisure roles are the new norms for aging persons. The changing demographic profile motivates us to anticipate new approaches to health care for an aging population. In the face of increasing longevity, the primary concern to be addressed is the development and administering of a system of services for the chronically ill. These health services must be coordinated to meet a range of needs from nutrition to hospice care, and yet to protect the individual and personal rights of the individual and to respond to the changing attitudes of the elderly as well as toward the elderly. PMID- 2237708 TI - Preventive care for the elderly. AB - While prevention has received a great deal of attention in the medical community in the last 15 to 20 years, little of this research or clinical activity has been addressed directly to the elderly population. Today, with an increasing emphasis on geriatric care, there is a rising awareness that clinicians' preventive efforts on behalf of the elderly can yield important benefits not only for individuals, by improving their quality of life, but also for society through potential cost savings. This chapter describes the effects of prevention strategies for the elderly. PMID- 2237707 TI - The aging workforce: implications for organizations. AB - Older workers may perform as well as or better than younger workers. Their accumulated knowledge, skills, and experiences, as well as their low absenteeism, turnover, and accident rates, makes them valuable employees. This chapter examines both the positive and negative effects of an aging workforce. A variety of issues regarding demographic trends, ageism, stereotyping of the older worker, appropriate health promotion strategies, elder care, and health care costs are addressed. PMID- 2237709 TI - Legal issues in the delivery of worksite health promotion. AB - Employee health promotion programs typically involve one or more of the following: (1) education programs, (2) cholesterol, blood pressure, diabetes, or other similar screening programs, (3) smoking cessation programs, (4) drug/alcohol testing and counseling programs, (5) exercise facility or activity programs, and (6) recreational activity programs. The authors examine potential legal implications of these activities. This chapter is intended for those attempting to define and establish these programs or to focus and operate them without undue conflict or legal system involvement. PMID- 2237710 TI - Are we there yet? Anticipating the future of worksite health promotion. AB - This chapter predicts future areas of concern for worksite health promotion programs. The shared responsibility of the employee and the organization in health promotion is stressed. The author also described the importance of recognizing the interrelationships among the personal domains of physical, emotional, mental, and spiritual health. PMID- 2237711 TI - The earnings test and the short-run work response to its elimination. AB - Eliminating the earnings test will have different effects on the work effort of persons aged 65-69, depending on whether or not they are currently working or currently receiving Social Security benefits. This article reviews the development of the earnings test and examines the theoretical implications on work effort of removing the test for members of this age group. It looks at the Current Population Survey (CPS) data to determine how many persons aged 65-69 have characteristics that can be identified with groups that would theoretically increase, decrease, or not change their work effort should they no longer be subject to the earnings test. This analysis suggests that at least 80 percent, and perhaps more than 90 percent, of the 9.7 million persons aged 65-69 will not change their level of work effort if the earnings test is eliminated. Individuals who would modify their hours worked and earnings are fairly evenly split among those who would increase, decrease, or have an undetermined direction of change in their work effort. PMID- 2237712 TI - Understanding depression in medical patients. Part I: Diagnostic considerations. AB - Little attention has been devoted to integrating theoretical conceptions of depression when considering patients with medical illness. This is more true of the social work literature than the psychiatric, in which medical formulations and treatment of depression gain primary focus. This paper presents an approach for understanding the phenomenon of depression in medical patients. It incorporates a theoretical perspective on the mechanism of depression relevant to social work intervention. Topics reviewed include diagnostic criteria for depression in the medically ill, organic factors in depression, and psychosocial theory of depression applied to medical patients. A second part of this paper will provide case examples and recommendations for social work intervention. PMID- 2237713 TI - Understanding depression in medical patients. Part II: Clinical intervention. AB - This paper presents case examples to illustrate key aspects of social work intervention with medical patients. Principles of clinical technique are discussed in relation to diagnosing and treating depression in the medically ill. This paper is a follow-up companion to "Understanding Depression in Medical Patients Part I: Diagnostic Considerations" and emphasizes the unique contribution of social work in the complex treatment of the biopsychosocial needs of individuals and families coping with physical illness. PMID- 2237714 TI - Enhancing patient participation: clinical strategies in the discharge planning process. AB - Social workers are in an excellent position to develop clinical interventions to enhance patient control over decision making about post hospital care. Participation in decision making has been identified in many studies as influencing well-being, health status and even mortality rates for elderly individuals facing relocation. Some of the practice patterns that support patient autonomy include: (1) involving the patient when working with families; (2) reaching for underlying conflict; (3) creating a sense of choice within existing parameters; (4) preparing patients for discharge; and (5) educating families and hospital caretakers to assist in this process. PMID- 2237716 TI - Beyond relationship: the current challenge in clinical practice. AB - Clinical social workers in health settings have used time and relationship and the understanding of individual and family dynamics, biophysiology, and larger systems issues to assist patients and families in resolving health related problems. The current economic crisis is limiting time and focus and necessitating revisions in intervention techniques. Clinicians experience this as a threat to their identity as a caring profession and to their ability to support patient autonomy within the health care environment. Effective adaptation requires a different use of self, expanded diagnostic skills, greater use of networking and systems interventions, and more sophisticated clinical techniques. Often, engagement, assessment and intervention have to occur within the same session. To accomplish this shift in practice, there has to be strong clinical leadership and a conscious focus on adapting clinical models to meet the current economic restrictions. PMID- 2237717 TI - Managing stress in health social work roles today. AB - Stress on social workers in health settings is of increasing professional interest and concern. This article suggests individual and system sources of such stress and outlines pathways for nurture of the authentic and creative self in health careers. Replenishing measures include empowerment through teamwork, stress management techniques, consciousness raising to alter self defeating cognitions, and activities within and outside the setting to enrich definition and use of self. PMID- 2237715 TI - Empowering families of the chronically ill: a partnership experience in a hospital setting. AB - An intervention model has been developed which teaches family members, in partnership with social workers, to obtain and monitor services for their chronically ill elderly relatives. The research site is a Boston teaching hospital with a patient population that is ethnically and racially diverse. Initial results of the study reveal that case management is easily accepted by most families, and the partnership between the family member and social worker enhances the delivery of needed services. PMID- 2237718 TI - The predictive value of needle localization mammographically assisted biopsy of the breast. AB - This study was done to review critically the experience at the University of California at San Diego in needle localization mammographic biopsy of the breast with regard to use and accuracy in identifying early carcinoma of the breast. Ninety-seven patients underwent needle localization mammographic biopsy of the breast between 1985 and 1987. Indications for this procedure included the presence of microcalcifications or a mass shown on mammographic examination, or both, in conjunction with physical examination which did not define a discrete abnormality in the area. Mammographic, demographic, pathologic, hormone receptor data and staging information were recorded and processed on the MicroVax II computer (Digital Equipment Corporation). Twenty-four per cent of lesions with needle localization mammographic assisted biopsy proved to be malignant. Sixteen lesions were diagnosed as an infiltrating ductal carcinoma and ten of these had an accompanying intraductal carcinoma. Over-all, intraductal carcinoma was present in 16 of the 23 specimens diagnosed as malignant. At biopsy, the margins were clear in 17 of 23, and vascular invasion was present in only one patient with an infiltrating lobular carcinoma. Five were tumor in situ, 12 were stage 1 and five were stage 2 (staging information was not available in one instance). Hormone receptor data were available in 17 of 23 specimens. Estrogen receptors were positive in 13 and progesterone receptors were positive in six. The smallest preinvasive malignant lesion was 4 millimeters, as seen on the mammogram, and the smallest free-standing invasive lesion was 8 millimeters. Preinvasive lesions (intraductal) presented as microcalcifications in 80 per cent. Invasive lesions presented as either a mass (n = 9) or as a mass and microcalcifications (n = 5) in 81 per cent. All five lesions presenting as both a mass and microcalcifications on mammogram proved to be malignant. Multifocal lesions on mammographic examination which proved to be malignant were multifocal pathologically in only 50 per cent. Needle localization mammographic biopsy is useful in detecting early carcinoma of the breast. Biopsy should be done on lesions presenting on mammogram as both a mass and microcalcifications and not observed. Focality of lesions on mammogram does not correlate with focality on biopsy and may be misleading as criteria for operative planning. PMID- 2237719 TI - Preventing postoperative acute bleeding of the upper part of the gastrointestinal tract. AB - Two hundred and ninety-eight critically ill patients at risk for the development of postoperative stress ulcers and bleeding were randomized into three groups. The first group comprised 85 patients who received meciadanol, a new bioflavonoid, 500 milligrams every six hours through a nasograstric tube; the second group comprised 100 patients who received sucralfate (crushed tablets), 1,000 milligrams every six hours through a nasogastric tube, and the third group comprised 113 patients who received an antacid (Maalox [magnesium aluminum hydroxide gel]) through a nasogastric tube at an initial dose of 15 milliliters every hour. The gastric pH was measured hourly and titrated to a pH greater than or equal to 4.0 in patients in the group receiving the antacid. The gastric pH was measured every two hours in the other two groups. Bleeding in the upper part of the gastrointestinal tract was determined visually (frank blood in gastric contents) or by guaiac testing. Bleeding occurred in seven patients receiving meciadanol, nine receiving sucralfate and six receiving the antacid. The difference in rates of bleeding was not statistically significant. Correlation between the severity of illness index and the development of bleeding was poor, at least in the low and intermediate index range. In contrast, there was a strong correlation between the age of the patient and the development of bleeding. Only one patient younger than 50 years had bleeding develop. Apparently, meciadanol exerts its action by a mechanism other than pH control. It may, therefore, fill an important gap in the ability to prevent postoperative stress ulcers and bleeding. PMID- 2237720 TI - Stapling or suturing for anastomoses of the left side of the large intestine. AB - Two hundred and fifty patients undergoing elective surgical treatment involving anastomoses of the left side of the colon or colon and rectum have been studied in a randomized trial in which the EEA (U. S. Surgical Corp.) circular stapler has been compared with single layer sutured anastomoses. Only patients in whom either technique was feasible were included in the analysis. The operative techniques were largely standardized. Patients were studied by means of a limited barium enema on the ninth or tenth postoperative day. The data have been analyzed for leakage rate (clinical and roentgenologic), other complications and degree of experience of the surgeon. Eleven patients were excluded from the analysis because the selected technique could not be carried out; of these, eight were in the stapled group in which it was possible to perform a sutured anastomosis. There were no instances in which it was possible to staple but not possible to suture. The remaining three exclusions were patients in whom either a coloanal anastomosis or a Hartmann procedure was performed. There was no over-all difference in the leakage rate--roentgenologic, clinical or total--between the two groups. However, when analyzed by the surgeon, the clinical leakage rate for surgeons in training was greater for sutured anastomoses than for stapled anastomoses (p = 0.053). Thus, it appears that the benefits of experience are more pronounced for sutured anastomoses but that, in experienced hands, neither technique is superior. PMID- 2237721 TI - Deleterious effects of testicular venous occlusion in young rats. AB - To determine the differences between testicular arterial and venous obstruction, the spermatic artery or vein, or both, were occluded for varying periods of time in young rats. Two months later, at the conclusion of the study, the testes were examined. Histologic degeneration after vascular obstruction was graded by a modified Johnsen's tubular biopsy score (TBS). The testicular concentrations of enzymes (lactic dehydrogenase and sorbitol dehydrogenase), known to decrease with testicular injury, were measured. TBS and seminiferous tubule diameter (STD) were found to decrease significantly after two hours of vascular occlusion and were similar regardless of whether the obstruction was produced by occlusion of arterial inflow or venous drainage, or both. Testicular concentration of enzymes decreased significantly after permanent ligation of the spermatic artery and vein, but decreased minimally when the vascular obstruction lasted less than 120 minutes. Testicular injury produced by venous occlusion was equally severe and occurred as rapidly as injury produced by arterial or combined arteriovenous occlusion. No significant injury was noted in the contralateral testes in any group. PMID- 2237722 TI - Intraoperative scintigraphy for active small intestinal bleeding. AB - Localizing active sites of bleeding within the small intestine remains a difficult task. Endoscopic, angiographic or scintigraphic studies may point to the small intestine as the site of blood loss, but at operation, without a palpable lesion, the exact site of bleeding remains elusive. Patients are managed at laparotomy with intraoperative endoscopy, angiography, multiple enterotomies, "blind" resections, or placement of an enterostomy. We describe two patients in whom intraoperative scintigraphy accurately identified active sites of bleeding in the small intestine when other modalities failed. Intraoperative scintigraphy is rapid, easy to perform and is an effective means of identifying active sites of bleeding within the small intestine. PMID- 2237723 TI - Time to recurrence varies inversely with thickness in clinical stage 1 cutaneous melanoma. AB - The thickness of a tumor has been identified as the principal prognostic factor in cutaneous malignant melanoma. However, time to recurrence has not conclusively been related to thickness. A retrospective study of 216 patients with a primary cutaneous malignant melanoma that recurred was conducted to clarify this relationship and investigate possible independent relationships between age at diagnosis and sex of patients to time to recurrence. The results of analysis of linear regression revealed an inverse linear relationship between thickness and time to recurrence (p less than 0.001). Patients more than 50 years of age at the time of diagnosis were shown to relapse sooner than those less than 50 years of age (p = 0.014). Sex was not a significant factor in predicting time to recurrence (p greater than 0.10). These results suggest that thickness of tumor provides an indication of time to recurrence in those patients destined to recur and stress the need for long term surveillance in patients with a history of malignant melanoma because of the possibility of late relapse even with thin lesions. PMID- 2237724 TI - Mediastinal tracheostomy using a pectoralis major myocutaneous flap after resection of carcinoma of the esophagus involving the proximal part of the trachea. AB - An operative procedure of mediastinal tracheostomy using a pectoralis major myocutaneous flap is presented. In this procedure, the terminal portion of the trachea penetrates through the center of a pectoralis major myocutaneous flap and the tracheal wall is completely wrapped with the muscular portion of the flap. Between 1981 and 1988, eight patients with carcinoma in the cervicothoracic segment of the esophagus underwent mediastinal tracheostomy after laryngoesophagectomy and extended resection of the proximal part of the trachea through sternal manubrectomy, because of invasion into the trachea. In five of eight patients, a pectoralis major myocutaneous flap was used to construct a tracheal stoma. A skin flap only, or both a skin flap and a muscle flap, was used in the other three. In four of eight patients, tracheal necrosis occurred, and rupture of the brachiocephalic artery occurred in one patient when the tracheal stoma had been constructed using both a skin flap and a muscle flap. However, neither skin breakdown nor bleeding from the major vessels occurred when using the myocutaneous flap. Therefore, it is concluded that the construction of the tracheal stoma using a pectoralis major myocutaneous flap is recommended for mediastinal tracheostomy after laryngoesophagectomy with extended resection of the proximal part of the trachea. PMID- 2237725 TI - Calcifications of the breast after reduction mammoplasty. AB - Mammograms of 152 patients after mammoplasty were studied and 37 patients were noted to have calcifications. The pattern of these calcifications was studied to determine if specific characteristics could be identified. The calcifications were found to occur within the skin of the breast, mainly at a periareolar location. The ability to identify these benign calcifications further aids in reliably monitoring patients by mammography after reduction mammoplasty. PMID- 2237727 TI - Use of inferior epigastric artery for reconstruction of a small accessory renal artery in renal transplantation. PMID- 2237726 TI - The justification for surgical treatment of metastatic melanoma of the gastrointestinal tract. AB - Fifty-six patients with symptomatic metastatic melanoma of the gastrointestinal tract (GIT) treated surgically at the Sydney Melanoma Unit between 1974 and 1989 were reviewed. The majority of these patients presented with abdominal pain or symptoms of anemia. The small intestine was the site of metastasis in more than 80 per cent. The mean over-all survival time was 11.7 months (range of one to 60 months) after surgical treatment of a first metastasis to the GIT and 3.6 months (range of zero to 12 months) postoperatively for a second GIT metastasis. Forty four of the patients reported complete relief of their symptoms postoperatively. The results suggest that an aggressive approach to symptomatic GIT metastases from malignant melanoma is justified both to relieve distressing symptoms and to prolong life. PMID- 2237728 TI - A safe and quick method for endoscopic retrieval of multiple gastric foreign bodies using a protective sheath. PMID- 2237729 TI - The contributions of John B. Murphy to thoracic surgery. AB - John B. Murphy was a prominent surgeon who lived in Chicago from the 1880s until his death in 1916. During his career, he was associated with both Rush Presbyterian and Northwestern Medical Schools. He was responsible for popularizing the use of an artificial pneumothorax as an effective adjunct in the treatment of pulmonary tuberculosis. This modality was not, however, his original concept. In addition to all of the fields of general surgery, Murphy undertook the management of empyema and lesions of the chest wall and also performed thoracoplasty procedures. Although he had done several thoracotomy procedures in his laboratory, he rarely undertook this operation in a clinical setting. Drop ether anesthesia was used for all surgical procedures. Murphy did not use closed water seal drainage of the chest. His oration on thoracic surgery, given at the annual meeting of the AMA, in 1898, was an excellent monograph on the subject and undoubtedly contributed to the increased interest and progress in this field of surgery. Murphy was a wise surgeon, an able technician and a scholarly teacher. The high regard in which he was held by his contemporaries is best expressed by the remark of William Mayo, "...he was the surgical genius of our generation". PMID- 2237730 TI - An overview of intimal hyperplasia. AB - Many hypotheses have been postulated for the development of intimal hyperplasia in vein and prosthetic grafts. In these hypotheses, the central theme seems to be endothelial injury, but not always denuding injury. As we progress into the biologic era with more sophisticated research tools, the study of the endothelial cell may give us the answers to the problem of intimal hyperplasia. In addition, the leukocyte is still a relatively unknown entity and further modification of their function may hold promise. PMID- 2237731 TI - Peptic ulcer medication usage, United States, 1989. AB - An estimated 10 percent of Americans at one time or another will have a peptic ulcer. Thus a class of specific ulcer medications (antisecretory drugs--ASDs) will continue to be an important part of the pharmaceutical market. The U.S. market for ASDs has increased more than 50-fold since their introduction 13 years ago. By 1989, seven ASDs were available in the U.S. and 42.6 million prescriptions were dispensed. New prescriptions accounted for 43 percent of this total. Per capita consumption varied substantially by state: Arkansas led with 162.9 per 1,000 and Nevada had the lowest rate (65.1 per 1,000). Zantac, manufactured in 1983, accounted for 44.1 percent of the 1989 market; Tagamet (available since 1977) followed with 28.2 percent of the market. Internists were the predominant source of the prescriptions and ASDs were prescribed for peptic ulcers 82.8 percent of the time. PMID- 2237732 TI - MetLife's experience with fitness and wellness programming. AB - MetLife converted a recreational gymnasium into a fitness and wellness facility designed to reduce the risk of cardiovascular disease in employees. Fitness assessments, customized workouts, and specialized classes were offered. One hundred and fifty-two employees who exercise regularly had initial and six-month fitness tests. This group's evaluation data showed favorable cardiovascular trends with decreases of 3.6 percent in resting heart rate, 6.4 percent in total cholesterol, 3.5 percent in systolic blood pressure, 2.8 percent in diastolic blood pressure and an increase of 2.7 percent in HDL cholesterol. Continuing analysis of the program will establish the efficacy of MetLife's Wellness and Fitness Program. PMID- 2237733 TI - AIDS: MetLife's experience. AB - The national health burden created by AIDS/HIV disease has had a significant impact on the insurance industry. In an analysis of the MetLife health and life insurance claims from 1986 through 1989, it was found that a total of $323,900,000 has been paid for AIDS/HIV disease. This figure and related information from those years were based on the Company's underwriting and claims files, with personal and group operations reported separately. Personal life insurance claims rose from 344 in 1986 to 874 in 1989 with the dollar amounts increasing from $3.2 million to $8.9 million. In 1989 there were 689 group life claims with a face amount of $31.5 million and 6,450 people who received group medical claim payments for a total of $111.2 million. In 1989 AIDS claims comprised 1.61 percent of MetLife claims--up from 0.4 percent in 1986. PMID- 2237734 TI - Forecast for the '90s: good health means better business. PMID- 2237736 TI - [Pressure distribution pattern in relation to foot structure during muscular active and passive load impacts]. AB - A piezoelectric pressure distribution platform (1000 elements) was employed, to investigate the mechanical behavior of three different foot structures. Ten male subjects in each of the foot groups Cavus, Rectus, and Planus performed voluntarily controlled jumps with one leg onto the pressure distribution platform. Using a trap door arrangement, the subjects fell in a second set of experiments unexpectedly onto the sensor matrix. In order to exclude a voluntary foot muscle response, the time duration of falling was restricted by choosing a falling height of only 20 cm. Comparing the data from both impact conditions the influence of active foot muscle involvement could be investigated. The analysis of the temporal pressure pattern, the local peak pressures and the regional impulses permitted an insight into the mechanical characteristics of the different foot structures. PMID- 2237735 TI - Modified radical mastectomies: average charges, 1988. AB - Average charge of $6,160 was billed to Metropolitan Life Insurance Company for 807 modified radical mastectomies during 1988. The average physicians' fees were $2,090. Length of hospital stay averaged 4.3 days across the country. The charges varied by as much as 92 percent between states. Among the 19 states included in the study, New York and California reported the highest average total charges ($7,870 and $7,290) and Iowa and Minnesota reported the lowest average charges ($4,100 and $4,620). On average, hospital expense comprised 66 percent of the total charges and ancillary fees accounted for almost three-fourths of the hospital bill. PMID- 2237737 TI - [Experiences with joint-preserving operations in arthrosis of the upper ankle joint]. AB - During a period of ten years we performed 140 joint conserving operations on patients with arthrosis of the ankle joint. The use of this procedure was analysed in 85 patients, whom we followed up. Mainly (in 89%) positive results were obtained. The success of such joint conserving surgery depends on the one hand on the seriousness of the injury leading to arthrosis and on the other hand on the duration of the complaints. If attention is paid to these factors we have after the failure of conservative therapy a satisfying complementary treatment before using the arthrodesis. PMID- 2237738 TI - [Therapy-resistant heel pain--an indication for surgery in sports traumatology]. AB - Posterior heel pain can be caused by inflammation or pathology of the achilles tendon, the tendon sheath, the retrocalcaneal and subcutaneous tendoachilles bursa, can be caused by osteophytes or stress fracture of the os calcis and by rheumatoid or metabolic diseases. The majority of patients can be treated successful nonoperatively; however, there is a small group of patients who are refractory to nonoperative managements. In the years 1984 to 422 patients with posterior heel pain were treated conservatively, 26 of these patients were refractory to that management. There were 9 cases of achilles tendinitis and/or tenosynovitis, 7 cases of bursitis, 3 cases of osteophyte of the os calcis. In 7 cases there was seen a combination of these three diseases. The following operative procedures were performed: discision of the tendon sheath, excision of thickened parts by inflammation, excision of degenerative and necrotic pain producing areas in the achilles tendon, excision of bursa and ostectomy of osteophyte at the posterior-superior angle of the os calcis. The mean follow-up was 2.7 years (range, 1/2 to 5 years). Overall there were 79% good results. In our opinion cases of posterior heel pain refractory to non-operative treatment are an indication of sports surgery, especially in patients who like to continue sports without pain. PMID- 2237739 TI - [Acute compartment syndrome of the anterior thigh caused by muscular overexertion]. AB - The object of this paper is to describe the problems of acute compartments syndromes, caused by muscular overexertion (in this case in the thigh) by a case report. Besides the description of the causes a potential pathomechanism in acute compartment syndrome, the authors discuss diagnostics, therapy and complications of these syndromes with due regard to the relevant scientific publications. PMID- 2237740 TI - [The value of arthroscopic labrum stapling in anterior shoulder dislocation]. AB - Shoulder luxations are common injuries in relation to sports. Isokinetic strength was evaluated in 24 patients on the average 1 year after performing arthroscopic stabilisation of an anterior shoulder luxation. Using the Merac (Universal Gym Equip., Cedar Rapids, Iowa, USA), test data were gathered on both shoulders in flexion-extension, abduction-adduction and in the supine 90 degrees abducted test position in external-internal rotation. Tests were performed at 60, 180 and 500 deg/sec. Means and standard deviations for peak torque, total work, peak torque to body weight ratios and agonist/antagonist ratios are presented. Our one year follow-up showed, that 82% of all patients were free from complaints and had almost the same data as on the non-operated shoulders. Arthroscopic stabilisation of anterior shoulder luxations in combination with intensive physiotherapy gave excellent results in most cases. PMID- 2237741 TI - [Ultrasonography of meniscus lesions]. AB - Controversy exists about the value of ultrasonography of meniscal tears. We therefore examined 101 knee joints of 99 patients in a prospective study. Prior to the arthroscopy the menisci were scanned from an independent team by using 7.5 and 10.0 MHz ultrasound waves. 81 meniscal tears were seen at arthroscopy; 36% of these tears could not be detected with the scanner (false negative results) while 20% of intact menisci showed positive echogenic structures, which were analysed as meniscal tears. It seems that ultrasonography of the menisci is still of experimental use without any clinical importance. PMID- 2237743 TI - [Position on "Results of diagnostic sonography in injuries of the knee joint"]. PMID- 2237744 TI - [20 years at the University Clinic for Radiotherapy and Radiobiology in Vienna (K.H. Karcher)]. PMID- 2237742 TI - [Results of diagnostic sonography in injuries of the knee joint]. AB - In an experimental study we examined three knee specimens with regard to the value of ultrasound for imaging soft tissue structures. Afterwards we documented artificial lesions of the menisci and ligaments. With this experience we started a prospective study of 101 patients suffering from acute knee injuries or chronic knee complaints. We compared the results of preoperative ultrasound investigation done by two different examiners with the final diagnosis after arthroscopy. For ultrasound evaluation we used a 5 MHz linear and a 7.5 MHz sector scanner. In both the experimental and the clinical study the menisci were well visualized. For medial meniscus lesions the less experienced examiner reached an accuracy and a predictive value of 81%. For the lateral meniscus the accuracy was 80%, although there was only a predictive value of 7% because of a high number of false positive results. The more experienced examiner got an accuracy of 83% and a predictive value of 91% for medial meniscus lesions. For the lateral meniscus the accuracy was 89%, however, the predictive value was only 22%. Both examiners were not able to detect ACL-ruptures surely. But ultrasound was useful to visualize Baker-cysts, bursitis, and jumpers-knee. PMID- 2237745 TI - [Brachytherapy using Ru-106 applicators in ophthalmology]. AB - Two Ru-106 applicators of the type CCB as manufactured by the "Zentralinstitut fur Isotopen- und Strahlenforschung" (Berlin, GDR) were investigated. The homogeneity of the relative dose distribution at the surface of the applicators was determined. For the evaluation of the data extremely small TLD crystals (2 x 1 x 1 mm) had to be manufactured as well as an almost tissue equivalent acrylic eye phantom. In order to assure reproducibility of the applicator positioning, the plaque suture eyelets had to be placed on locating pins. 120 points of measurements located within the active plaque area of 20 mm diameter were evaluated. The results show that the area to be used in tumor treatment is about 20 to 25% less than expected. One plaque shows a considerable inhomogeneity with respect to dose distribution (up to 40%). A modified eye phantom was used for the determination of the central axis depth dose distribution. PMID- 2237746 TI - [Increasing the thermal enhancement ratio by simultaneous application of radiation and hyperthermia--technical possibilities in interstitial application]. AB - Whereas the cytotoxic effect of hyperthermia is independent and without any time relationship with the radiation treatment, the heat induced radiosensitization only appears with simultaneous application of radiation and heat. Although the highest thermal enhancement ratio (TER) can be achieved with simultaneous application this protocol is not used in clinical practise because of technical problems. From a practical point of view the major effect of a non simultaneous application will have to rely on hyperthermic cytotoxicity. A two-zone needle which offers the possibility to conduct radiation and heat simultaneously in order to confine this to a three-dimensional radiation and heat is described. PMID- 2237747 TI - [The effect of 5-fluorouracil on the radiosensitivity of granulocytopoietic stem cells in the bone marrow and the blood]. AB - The radiation tolerance of haematopoietic stem-cells, originating from blood and bone marrow, after exposure to 5-Fluorouracil (5-FU) was investigated. The CFU-C Colony Formation Test was used to determine the surviving fraction of cryopreserved mononuclear bone marrow and blood cells, after incubation in culture medium containing 1 ng/ml 5-FU for 24 hours. With the same assay system we determined the radiation tolerance of peripheral CFU-C from three patients before and after 5-FU radio-chemotherapy (1000 mg/m2/24 h per day for four days), while the influence of the small radiotherapeutic treatment volume was neglected. Neither in the in vitro experiments nor in the patients we found a significant variation of the dose-survival curves with or without 5-FU. So it is concluded, that the enhanced myelodepression of 5-FU combined with radiation may be due to an additive effect or by effects on the microenvironment or on the pluripotent stem cell system. PMID- 2237748 TI - [Interstitial radiotherapy of breast cancer. Preliminary report of a prospective study of 165 cases subjected to breast-conserving treatment]. AB - The results of a prospective study on breast conserving therapy in early stage breast cancer are presented. From January 1983 to June 1987 165 patients were treated by a standardized therapy-protocol. The criteria for entering the trial were stage T1 to T2 and N0 to N1. Surgical breast conservation was achieved by segmental resection in 148 cases and by tumorectomy in 17 cases. 160 patients underwent axillary lymph node dissection. Obligatory 45 to 50 Gy were delivered percutaneously to the operated breast and optional 50 Gy to the regional lymph nodes (axillary lymph node involvement greater than 3 nodes). In addition, the area of the primary breast lesion itself was boosted interstitially by an Iridium 192 implant (LDR-technique: 15 to 20 Gy, HDR-technique: 10 to 12 Gy). RESULTS: Progression of disease in 10% of the patients (16/165), local recurrence rate in the operated breast: 2% (3/165), axillary recurrence: 0.5% (1/165). 5% of the patients (8/165) died from metastatic disease, two patients died free of recurrence for reasons unrelated to cancer, two other patients died on unknown reasons. Because of the low number of local recurrences and the observation period of 32 months, no statistically contribution on high risk factors for local failure could be found. PMID- 2237749 TI - [Therapy monitoring and after care of irradiated anorectal cancer using transrectal sonography]. AB - Pretherapeutic staging before radiotherapy and peri- and posttherapeutic endosonographic screening was carried out on 33 patients with anorectal carcinoma. The results showed the transrectal endosonography to be essential for staging and for the differential diagnosis of tumor recurrence/post irradiation changes during follow up. The sonomorphological criteria of tumor recurrences and post irradiation bowel wall changes are discussed. PMID- 2237750 TI - [Oxygen consumption during photodynamic therapy in vitro]. AB - The consumption of dissolved molecular oxygen was measured during photodynamic therapy in vitro. Aqueous solutions of hematoporphyrin derivative (HpD) containing different concentrations of serum or numbers of cells were prepared. Decrease in oxygen in the solution and cell suspensions was monitored during light-irradiation (at a wavelength of 610 to 640 nm). The rate of oxygen consumption increased with increasing concentrations of HpD, serum levels or numbers of cells. Upon repeated irradiation of the same solutions (after restitution of the initial pO2 of 100 mm Hg), the rate of oxygen consumption decreased indicating a disaggregation process of HpD. The rate of oxygen content of the solutions decreased independently of the actual oxygen partial pressure. Even at a low pO2 below 10 mm Hg, oxygen consumption was unimpeded until the solutions were free of oxygen. No O2-consumption was noted in aqueous solutions of HpD (up to 40 g/ml) without serum or cells during irradiation. PMID- 2237751 TI - [Chemo- and radiosensitivity testing of tumor tissue cultured in vitro. Development of a fiber culture system for cell harvesting]. AB - Chemo- and radiosensitivity-testing of tumour cells should be performed in vitro under in vivo-like conditions. One problem is to grow cells to tissue-like cell densities in vitro. A hollow fiber reactor was prepared for cell growth to high densities. In order to obtain cells during and after sensitivity testing for quantitating cell damage, a harvesting fiber system was developed which can be inserted in the nutritional hollow fiber system. These hollow fibers have a diameter of 300 microns and a wall thickness of 10 microns. Small holes between 10 and 100 microns can be cut into the fibers for cell harvesting by electric sparks. Up to 60 holes per mm fiber length can be produced. PMID- 2237752 TI - [Retrobulbar irradiation of endocrine ophthalmopathy: a comparison between 10 and 16 Gy total dose]. AB - Severe Graves' ophthalmopathy has been treated in 44 cases by orbital irradiation. 36 out of 37 patients showed a good response or a suspend of the progressive disease. In 17 out of 33 primary irradiations a dose of 10 Gy and in 16 cases a dose of 16 Gy was applied. Measured by ophthalmopathy-index significant better results have been achieved by a total dose of 16 Gy. Because of recurrence after primary irradiation of 10 Gy a re-irradiation became necessary in 35% of the cases. Primary irradiation of 16 Gy has required no further treatment during the same time of observation. A single series of 16 Gy irradiation has shown better results than two series of 10 Gy irradiation concerning the proptosis and alleviation of symptoms. PMID- 2237753 TI - Multi-modality in management of primary malignant non-Hodgkin lymphomas of the central nervous system. AB - A retrospective study of nine patients with primary malignant non-Hodgkin lymphomas of the central nervous system was carried out with emphasis on treatment results. Detailed investigations before or during the treatment excluded the presence of extraneural malignant lymphoma. The varying radicality of surgery was followed by radiotherapy, with different doses and techniques occasionally with adjuvant drug treatment. Two patients received chemotherapy. Surgical removal and subsequent radiotherapy as well as the histology were almost identical in patients with longer survival. It was tried to evaluate the prognostic influence of different factors on treatment and survival. PMID- 2237754 TI - [Therapy of medulloblastomas--results from 1968 to 1985]. AB - Between 1968 and 1985 35 patients with an histological proven medulloblastoma received radiotherapy after surgery. Patients are divided into three groups, showing the improvement in diagnostic procedures as well as in therapy. These changes result in a higher proportion of patients living longer without disease. Only a close cooperation between surgeon, radiotherapist and pediatric oncologist will give these patients the best chances of cure, if they are treated in multicenter studies. PMID- 2237755 TI - [A new system for cervix application using the afterloading technique]. AB - We developed a new application system for the intracavitary afterloading therapy of the cervix carcinoma. With this system special problems of the application as the possible perforation of the cervix uteri are prevented. PMID- 2237756 TI - [Simple endoscopic positioning of a double-barrelled afterloading applicator based on the Seldinger principle]. AB - The endoluminal positioning of afterloading applicators without exact guidance may be time wasting and difficult in cases of unsteady or higher degree gastroenterological tumor stenosis. The open catheters, which were developed especially for this, will be pushed over a guidewire and have an obligatory contamination of catheter and radiation source with body secretions. For this case we have developed a double channeled afterloading applicator, which will give the advantages of the Seldinger technique with the safety of a closed system, combined with endoscopic guiding of the wire. With this technique we simplified the endoluminal radiation. Our method is safe, time saving and less stressful for the patients. PMID- 2237757 TI - Cataract extraction in uveitis patients. AB - Cataracts are known to develop at an accelerated rate in many forms of uveitis. Until recently, cataract surgery in such eyes was regarded as a hazardous procedure that yielded unpredictable and often discouraging results. Recent evidence from a number of reports suggests that newer surgical techniques and careful medical management allow a significant number of patients with uveitis to undergo cataract extraction successfully. Intraocular lens implantation using in the-bag posterior chamber lens technique has been successful in selected cases. Careful patient selection, coupled with the use of an appropriate surgical technique, appear to be of major importance. Herein we review the current literature on cataract extraction in uveitis and provide guidelines for patient and technique selection based on the type of inflammation present. The management of common surgical problems and complications is discussed, as is the role of the intraocular lens. Specific surgical techniques useful in the management of eyes with cataract and uveitis are discussed. PMID- 2237758 TI - Antibodies in human tears during and after infection. AB - The tear content of antibodies specific for various infectious agents has recently begun to be investigated. Important parameters of tear analysis with respect to antibody content are the method of tear collection and the laboratory techniques used to detect specific antibodies in the lacrimal fluid. Normal tears contain antibodies directed against both bacteria and viruses, and the antibody response in lacrimal fluid during immunization of animals and humans has been studied to some extent. This response has also been analyzed in humans during and after natural infection with certain viral and bacterial pathogens. It has become clear that local antibody synthesis takes place in the lacrimal gland, but at least some of these antibodies appear in tears because of lymphocyte sensitization in the common mucosal immune system. A certain degree of transudation of serum antibodies to tears is also often encountered, especially in severely inflamed eyes. Much of the data currently available needs to be confirmed, and more extensive studies need to be carried out for many pathogens. Potential benefits of such studies include development of new diagnostic techniques as well as a better understanding of when and how antibodies confer protection or may be potentially damaging. PMID- 2237759 TI - Disc swelling in an adult diabetic patient. AB - A patient with insulin dependent adult onset diabetes presented with bilateral disc edema and minimal visual dysfunction. Initial work-up excluded an intracranial lesion, and a lumbar puncture revealed a normal opening pressure. The patient developed proliferative retinopathy, for which she received photocoagulation therapy. She subsequently developed an exacerbation and change of her disc swelling, associated with raised intracranial pressure. The differential diagnosis of diabetic papillopathy and papilledema is discussed. PMID- 2237760 TI - Caspar Stromayr: sixteenth century ophthalmologist. AB - Caspar Stromayr, ophthalmologist and hernia surgeon, is credited with writing the first German ophthalmic work of known authorship. Written in about 1559 as an appendix to Practica Copiosa, a larger work on hernia surgery, the ophthalmic chapters describe Stromayr's thoughts on the etiology and treatment of cataract. Stromayr, a master craftsman, also expresses his hostility to the shams and ignorance of the charlatan eye surgeons of his day. This interesting historical article provides a biographical sketch of Stromayr, a description of his book, and a translation of two chapters, "On Cataract of the Eye: How They Take Their Beginning and Whence they Come" and "How You Recognize the Cataract, When It is Ripe to Recline or to be Taken Away." PMID- 2237761 TI - Congenital craniofacial anomalies of ophthalmic importance. AB - Congenital craniofacial abnormalities frequently require ophthalmic evaluation and surgical management. Called upon to perform as part of the craniofacial team managing the often severely deformed craniofacial patient, the ophthalmologist must bring a basic knowledge of craniofacial syndromes and developmental anatomy, as well as clinical acumen to help preserve or improve ocular and adnexal function. As an introduction to this area of ophthalmology, the clinical features, classification, appropriate facial embryology, assessment and surgical considerations of the various congenital craniofacial abnormalities are reviewed. The expanding availability of craniofacial surgeons and surgical teams along with improved surgical results will ultimately require an increasing involvement by many more ophthalmologists in the evaluation and management of these congenital abnormalities. PMID- 2237762 TI - High or low hepaticojejunostomy for bile duct strictures? AB - The 19 patients who underwent 22 postoperative repairs of bile duct stricture in our institution between 1973 and 1984 were evaluated to assess whether the recognition of the tenuous blood supply of the supraduodenal bile duct in 1979 had improved the results thereafter. Thirteen of these 22 operations followed a previous biliary tract repair; in 10 of the operations a low anastomosis had been performed without taking blood supply into account. Follow-up was complete and ranged from 5 to 15 years. There were no operative deaths and minimal morbidity. There were three deaths at a later time. Five of the 11 patients treated by surgery to 1979 had a clinically unsatisfactory result: recurrent strictures developed in all five patients. All but one of the eight patients receiving a high hepaticojejunostomy from 1980 had a clinically satisfactory result with no recurrent strictures. The one exception was the patient who had a second repair with separate high right and left hepatic duct anastomoses and who has ongoing symptoms from preexisting secondary sclerosing cholangitis. The results in the five high repairs performed for low strictures were particularly striking: All five were asymptomatic. This study lends support to the hypothesis of an ischemic basis for biliary strictures and to the recommendation that strictures be repaired with a high hepaticojejunostomy. PMID- 2237763 TI - Biliobiliary fistula: preoperative diagnosis and management implications. AB - Experience with cholecystohepaticodochal and cholecystocholedochal fistulas as a result of an erosion of gallstones from the gallbladder into the adjacent common duct in five patients is presented. The incidence was 1.4% in a population of 350 patients undergoing cholecystectomy. The condition was indicated clinically on the basis of a symptom triad of jaundice, fever, and pain with cholelithiasis in a small contracted gallbladder. In addition, proximal intra- and extrahepatic ductal dilatation, calculus in the common duct, and normal-caliber (or unprofiled) distal common duct on ultrasound scan were present in all the patients. Endoscopic retrograde cholangiopancreatography proved to be the most useful means of investigation, and it confirmed the diagnosis in four patients before surgery. A modified antegrade cholecystectomy was performed with the gallbladder opened inferiorly at the fundus, and the stones were evacuated. A partial cholecystectomy and choledochoplasty were accomplished with gallbladder flaps whenever feasible. Other useful operative procedures are side-to-side hepaticodochojejunostomy and hepaticodochoduodenostomy. In the presence of high benign bile duct stricture, an approach to the left hepatic duct is now preferred for biliary bypass. PMID- 2237764 TI - Hyperbaric oxygen therapy for necrotizing fasciitis reduces mortality and the need for debridements. AB - Twenty-nine patients with necrotizing fasciitis were treated from 1980 to 1988. This study evaluates how the addition of hyperbaric oxygen (HBO) therapy to surgical treatment has affected mortality and the number of debridements required to achieve wound control in these patients. Two groups of patients were viewed: group 1 (n = 12) received surgical debridement and antibiotics only; group 2 (n = 17) received HBO (90 minutes at 2.5 atm, average 7.4 treatments) in addition to surgery and antibiotics. Both groups were similar in age, race, sex, wound bacteriology, and antimicrobial therapy. Body surface area affected was similar, however, perineal involvement was more common in group 2 (53%) than in group 1 (12%). The admitting conditions of patients in group 1 (non-HBO) were diabetic, 33%; white blood cell count more than 12,000, 50%; and shock, 8%. The admitting conditions of patients in group 2 (HBO) were diabetic, 47%; white blood cell count more than 12,000, 59%; and shock, 29%. Although group 2 patients receiving HBO were more seriously ill on admission, mortality was significantly lower (23%) compared to group 1 (66%) (p less than 0.02). In addition, only 1.2 debridements per group 2 patient were required to achieve wound control versus 3.3 debridements per group 1 patient (p less than 0.03). The addition of HBO therapy to the surgical and antimicrobial treatment of necrotizing fasciitis significantly reduced mortality and wound morbidity (number of debridements) in this study, especially among nonclostridial infections. We conclude that HBO should be used routinely in the treatment of necrotizing fasciitis. PMID- 2237765 TI - The role of gastric resection in the management of multicentric argyrophil gastric carcinoids. AB - A patient with pernicious anemia, atrophic non-antral gastritis, hypergastrinemia, and widespread hyperplasia of enterochromaffin-like cells and manifest enterochromaffin-like cell carcinoma was followed up during 39 months, including 15 months after gastric resection. In this case normalization of gastrin levels did not prevent the development of multiple gastric carcinoids in the fundic mucosa, suggesting that factors other than gastrin are of importance in the pathogenesis. PMID- 2237766 TI - Myoelectric effects and histology after stapled occlusion of the small bowel. AB - Braun enteroenterostomy with stapled occlusion of the afferent limb has been advocated to treat bile gastritis and to avoid the motility effects of Roux-en-Y gastrojejunostomy. However, the motility effects of stapled occlusion are unknown. Myoelectric activity and histologic features were studied after stapled occlusion of the small bowel in a canine model. A 35 cm "recirculating loop" was created with a side-to-side anastomosis, beginning 25 cm from the ligament of Treitz. Serosal electrodes were placed at 5 cm intervals on the loop; at a second operation in one dog and simultaneously in three dogs, the bowel was occluded midway between two electrodes with 4.8 mm staples. Fasting recordings were obtained at weekly intervals to 6 months after surgery and were analyzed for slow wave frequency proximal and distal to the staple line and for propagation time of phase 3 of the migrating myoelectric complex across the staple line. The side-to side anastomosis did not alter myoelectric activity. However, after stapled occlusion of the small bowel, the slow wave frequency dropped from a mean of 18.2 +/- 0.4 cpm proximally to 15.4 +/- 1.0 cpm distally (p less than 0.05). This correlated with loss of myogenic continuity in three of four animals. Propagation of phase 3 slowed across the staple line (115 +/- 27 seconds versus 47 +/- 9 seconds) (p less than 0.02). The bowel lumen recannulated in all animals. Stapling across the small bowel alters myoelectric activity, and occlusion of the bowel lumen may not be permanent. PMID- 2237767 TI - Traumatic disruptions of the thoracic aorta: treatment and outcome. AB - Of 27 patients admitted to our level I trauma center with acute disruption of the thoracic aorta, two patients died of exsanguination before aortic repair. One patient had massive leakage from the aneurysm after aortography and died during surgery. All patients suffered from multiple injuries. Eighty-three percent of the patients had major operations in addition to the aortic repair. "Clamp and sew" technique was used in 18 patients (75%), two of whom had multiple tears of the aortic arch. Heparin-coated shunts were used in five patients (20.8%), and a cardiopulmonary bypass was performed in one patient who had multiple tears. Three postoperative deaths were related to polytrauma, cardiogenic shock, and sepsis. Paraplegia developed in three patients, two of whom had multiple aortic lesions necessitating longer ischemia time during the repair. Only one patient had complete neurologic deficit at the 1-year follow-up. In our series, neither surgical procedure proved superior. We conclude that the "clamp and sew" technique for repair of the disrupted thoracic aorta may allow for a more favorable outcome. PMID- 2237768 TI - Sequential gradient pneumatic compression enhances venous ulcer healing: a randomized trial. AB - The treatment of venous ulcers has remained largely unchanged for centuries. The application of properly applied graduated compression bandages, the use of graduated compression stockings, and surgery have been shown to achieve healing. However, some ulcers persist despite appropriate management. A randomized study was undertaken to compare two regimens of treatment for such patients. Both regimens included ulcer debridement, cleaning, nonadherent dressing, and graduated compression stockings. In one regimen, sequential gradient intermittent pneumatic compression was applied for 4 hours each day. Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group. The median rate of ulcer healing in the control group was 2.1% area per week compared to 19.8% area per week in the intermittent pneumatic compression group. The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers. PMID- 2237769 TI - Esophageal reflux before and after isolated myotomy for achalasia. AB - Four patients with achalasia underwent 24-hour esophageal pH measurements as ambulatory patients before and after limited myotomy without fundoplication. Resting lower esophageal sphincter pressure was reduced from 24.3 +/- 1.3 mm Hg to 7.5 +/- 4.3 mm Hg. No significant differences (p greater than 0.05) were found before and after operation in the total 24-hour pH data distribution (pH 6.24 +/- 0.84 vs 5.75 +/- 1.03), the fraction of time below pH 4.0 (4.8% +/- 5.3% vs 8.0% +/- 6.9%), or the mean duration of reflux episodes greater than 5 minutes (22.8 +/- 18.8 minutes vs 23.0 +/- 10 minutes), all +/- SD. Effective relief of esophageal obstruction in achalasia is feasible by isolated limited myotomy without producing gastroesophageal reflux. PMID- 2237770 TI - Rejection of multivisceral allografts in rats: a sequential analysis with comparison to isolated orthotopic small-bowel and liver grafts. AB - Multivisceral isografts and allografts were transplanted to Lewis rats, and the histopathologic changes were studied in the liver, intestine, and other constituent organs. Rats receiving isografts had indefinite survival with maintenance of weight. With multivisceral allografts (from Brown-Norway donors), the intestinal component was rejected more severely than the companion liver and with about the same severity as when intestinal transplantation was performed alone. Intestinal rejection in either circumstance was a lethal event, causing death in 10 to 12 days. The earliest (by day 4) and most intense cellular rejection was in the Peyer's patches and mesenteric lymph nodes. This was associated with or followed by cryptitis, epithelial cell necrosis, focal abscess formation, mural necrosis, and eventual perforation. Liver allografts transplanted alone or as part of multivisceral grafts also had histopathologic evidence of rejection, but this was self-limiting and spontaneously reversible when the liver was transplanted alone. Thus the Achille's heel of multivisceral grafts is the intestinal component that is not protected by the presence of the liver in the organ complex. Better immunosuppression should permit successful experimental and clinical transplantation of such grafts. PMID- 2237771 TI - Improved preservation of the rat liver for orthotopic liver transplantation: use of University of Wisconsin-lactobionate solution and retrograde reflushing. AB - This study investigated cold preservation and reflushing before orthotopic liver transplantation by examining (1) new University of Wisconsin solution (UW) versus Euro-Collins solution (EC), (2) retrograde reflushing (RR) versus antegrade reflushing (AR), and (3) the addition of a platelet-activating inhibitor (PAF), superoxide disumatase (SOD), or SOD + catalase to UW. Syngeneic, male Lewis rats (200 to 400 gm) were used. Preservation for 9, 12, 18, or 24 hours in UW or EC with RR (through the inferior vena cava) was used. The 9- and 12-hour groups experienced a significant decrease in the weight of the grafts preserved in UW. The 3-week survival rate after 9 hours of preservation (n = 6) in UW was 66%, and the survival rate with EC was 0% (p less than 0.025). After 12 hours of preservation, recipient survival rate was 70% (n = 10) with UW versus 0% (n = 4) with EC (p less than 0.025). RR of the graft with cold lactated Ringer's solution immediately before reimplantation significantly improved 3-week survival in the 12-hour group to the level of the control group (no preservation time, 69%). Preservation for 12 hours in UW followed by AR yielded a 3-week survival of 14%; 3-week survival for the RR group was 70% (p less than 0.025). Furthermore, RR allowed a 3-week survival of 33% and 20% after 18 and 24 hours of UW preservation, respectively. In the 24-hour RR/UW group, donor pretreatment with SRI 63-441 (20 mg/kg, intravenously) and recipient treatment with SOD (15 mg/kg, intravenously) or SOD + catalase (15 mg/kg and 5000 units/kg, intravenously) produced a 3-week survival comparable to preservation in UW followed by RR alone. These studies show that UW is a profound improvement over EC for cold preservation of liver and that the new application of RR to rat orthotopic liver transplantation improves survival. However, the addition of free-radical scavengers or PAF does not improve organ function or recipient survival in this model. PMID- 2237772 TI - Portal vein resection with a new antithrombogenic catheter. AB - Curative resection of pancreatic and hepatobiliary tumors is rarely possible because of local invasion, especially into the portal vein. We developed a new antithrombogenic catheter using a heparinized hydrophilic polymer to allow portal vein bypass during resection of tumors invading the portal vein. Pancreatectomy or hepatectomy accompanied by portal vein resection was performed for pancreatic or hepatobiliary cancer, with an intraoperative shunt from the superior mesenteric vein to the femoral vein or from the superior mesenteric vein to the intrahepatic portal vein through the umbilical vein or the hepatic hilar portal vein. Use of the shunt prevented stasis in the superior mesenteric vein and hepatic ischemia even during prolonged occlusion of the portal vein, and portal vein resection was performed in 81 patients with hepatobiliary and pancreatic disease with greater safety and ease. PMID- 2237773 TI - Adoptive immunotherapy of human pancreatic cancer with lymphokine-activated killer cells and interleukin-2 in a nude mouse model. AB - A pancreatic cancer cell line was grown in orthotopic and heterotopic positions in young Swiss/NIH nude mice, which were tested with adoptive immunotherapy. Mice were injected with 1 x 10(7) human cancer cells in the subcutaneous tissue and duodenal lobe of the pancreas. The mice were randomly divided into four groups: group IA (LAK + IL-2) (N = 25) received 2 X 10(7) human lymphokine-activated killer (LAK) cells from normal donors by tail vein injection followed by 10,000 units of human recombinant interleukin-2 (IL-2) given intraperitoneally every 12 hours for 28 days; group IB (IL-2) (N = 27) was given the same dose of IL-2 alone; group IC (RPMI-1640) (N = 18) received a placebo consisting of 1 ml of RPMI-1640 intraperitoneally every 12 hours; and group ID (LAK) (N = 14) received 2 X 10(7) LAK cells but no IL-2. Toxicity was significantly higher in group IB, with a mortality rate of 45.5% (10/22 animals) versus a 0% mortality (0/25) in group IA. None of the group IA or IB animals died of pancreatic cancer during the experiment. The animals that did not receive IL-2 died before 28 days in 14.2% of group IC and in 16.7% of group ID. The area under the growth curve of subcutaneous tumors during the course of treatment and the pancreatic tumor weight at the end of treatment were compared in each group. Subcutaneous tumors had a reduced rate of growth in group IA animals compared to all the other treatments. Pancreatic tumor growth was slowed in group IA. The animals treated with IL-2 alone (group IB) showed some slowing of tumor growth that was intermediate between group IA, group IC, and group ID. A similar experiment was done with irradiated (375 rad) mice. Nine nude mice with tumors were treated with LAK + IL-2 (group IIA), eight received IL-2 alone (group IIB), and seven received placebo (group IIC). The antitumor effect of IL-2 alone was not present in the irradiated mice. A highly significant difference persisted between group IIA and all other groups. There was no difference in the histologic characteristics of tumors in control mice and in mice with inhibited tumor growth treated with IL-2 or IL-2 and human LAK cells. These results show that adoptive immunotherapy with human LAK cells and human recombinant IL-2 is effective against human pancreatic cancer growing in nude mice. This effect is independent from antitumor activity from IL-2 administrations alone. PMID- 2237774 TI - Gastric outlet obstruction caused by traumatic pseudoaneurysm of superior mesenteric artery. AB - Traumatic pseudoaneurysms of the superior mesenteric artery (SMA) are extremely rare. We describe two cases of posttraumatic proximal SMA pseudoaneurysms with symptoms of gastric outlet obstruction. Repair was accomplished by aorta-SMA bypass with saphenous vein. Injuries to the proximal SMA are easily missed at laparotomy, especially if intestinal ischemia or hematomas are absent. Recognition and repair are stressed to avoid the complications associated with pseudoaneurysm formation. PMID- 2237775 TI - Severe primary hyperparathyroidism in a neonate having a parent with hypercalcemia: treatment by total parathyroidectomy and simultaneous heterotopic autotransplantation. AB - Neonatal primary hyperparathyroidism is a life-threatening disease because of marked hypercalcemia and severe respiratory distress caused by the hypoplastic thorax and occasional rib fractures. We report a 29-day-old girl treated by total parathyroidectomy and simultaneous autotransplantation of parathyroid tissue (one fifth of each of the two glands) in the femoral quadriceps muscle near the groin. At the time of operation, all four of the parathyroid glands were markedly enlarged, and their total weight was 900 mg. Part of the resected parathyroid tissue was cryopreserved for further autotransplantation should hypoparathyroidism develop. Two years six months after surgery, the infant was well and had normal levels of serum calcium and immunoreactive parathyroid hormone in the absence of any supplementary treatment. Asymptomatic hypercalcemia in the presence of abnormally low fractional excretion of calcium was found in the father. Based on our experience and review of the literature, we recommend total parathyroidectomy, autotransplantation, and cryopreservation for the neonate with primary hyperparathyroidism. PMID- 2237776 TI - Cholinergic modulation of responses to single tones produces tone-specific receptive field alterations in cat auditory cortex. AB - Acetylcholine (ACh), acting via muscarinic receptors, is known to modulate neuronal responsiveness in primary sensory neocortex. The administration of ACh to cortical neurons facilitates or suppresses responses to sensory stimuli, and these effects can endure well beyond the period of ACh application. In the present study, we sought to determine whether ACh produces a general change in sensory information processing, or whether it can specifically alter the processing of sensory stimuli with which it was "paired". To answer this question, we restricted acoustic stimulation in the presence of ACh to a single frequency, and determined single neuron frequency receptive fields in primary auditory cortex before and after this pairing. During its administration, ACh produced mostly facilitatory effects on spontaneous activity and on responses to the single frequency tone. Examination of frequency receptive fields after ACh administration revealed receptive field modifications in 56% of the cells. In half of these cases, the receptive field alterations were highly specific to the frequency of the tone previously paired with ACh. Thus ACh can produce stimulus specific modulation of auditory information processing. An additional and unexpected finding was that the type of modulation during ACh administration did not predict the type of receptive field modulation observed after ACh administration; this may be related to the physiological "context" of the same stimulus in two different conditions. The implications of these findings for learning-induced plasticity in the auditory cortex is discussed. PMID- 2237777 TI - Chronic treatment with clozapine or haloperidol differentially regulates dopamine and serotonin receptors in rat brain. AB - Long-term administration of the atypical neuroleptic clozapine (CLZ) poses a much lower risk of extrapyramidal side effects (EPS) than does the use of typical neuroleptics such as haloperidol (HAL). To investigate the neural mechanisms of the differing CNS activities of these two drugs, we used quantitative autoradiography to measure changes in dopamine and serotonin receptors in rats after injection with CLZ or HAL for 21 days at clinically relevant dose ratios. Levels of D1, D2, and 5-HT2 receptors were determined in frontal cortex, caudate putamen, and nucleus accumbens. Rats that received CLZ chronically showed CNS receptor changes markedly different from those in chronic HAL-treated animals. Whereas rats treated chronically with HAL showed enhanced striatal D2 binding (average increase of 42%), those treated with CLZ did not. In contrast, chronic CLZ, but not chronic HAL, induced enhanced striatal D1 binding (average increase of 43%). Finally, CLZ treatment decreased 5-HT2 receptor binding by an average of 37%, while HAL had no significant effect. The effects of chronic HAL or CLZ treatment on receptors were similar in all forebrain areas examined. However, since D1 and 5-HT2 receptors are more abundant than D2 sites in limbic and neocortical areas, the preferential modulation of D1 and 5-HT2 receptors by CLZ suggests a greater impact of this atypical neuroleptic on activity of the limbic system than that achieved by the typical neuroleptic, HAL. These findings suggest that the clinical profile of atypical neuroleptics such as CLZ may be attributed to their effects on a receptor profile differing in pharmacological characteristics and anatomical distribution from that affected by typical neuroleptics. PMID- 2237778 TI - Modulation of gonadotropin-releasing hormone neuronal activity as evidenced by uptake of fluorogold from the vasculature. AB - Peripheral injections of the tracer fluorogold (FG) and immunocytochemistry were used to study the modulation of gonadotropin-releasing hormone (GnRH) cell secretory activity in adult mice. Intraperitoneal administration of FG would make it available to all GnRH terminals outside the blood-brain barrier. The degree of capture of the dye would be linked to exocytotic (e.g., secretory) events at the nerve terminal. Single injections of tracer were made into intact mice of both sexes, and this resulted in the retrograde labeling of two-thirds of the GnRH cell bodies. Administration of identical doses to 3 week castrate mice revealed a reduction in the percentage of GnRH cells, with detectable FG, to 40% of the total. Castration did not diminish the number of GnRH cells visualized. When castrate animals received two doses of FG, the number of GnRH cells with tracer was increased to slightly greater than intact levels. This suggests that the secretory rate of individual GnRH cells might be reduced under conditions of castration. In addition, when ovariectomized females treated with estrogen and progesterone to induce luteinizing hormone (LH) surge were injected with FG just prior to that surge, over 80% of the GnRH neurons were robustly labeled with FG. These latter data are interpreted as representing GnRH neurons at maximally synchronized activity. This study suggests that peripheral administration of FG can be used in this species to follow alterations in neurosecretory rates. PMID- 2237779 TI - Electrophysiological identification of a pathway from the septal area to the medial amygdala: sensitivity to estrogen and luteinizing hormone-releasing hormone. AB - Medial amygdala neurons responsive to electrical stimulation of the medial septal area were electrophysiologically identified in ovariectomized, urethane anesthetized female rats. Peristimulus time histograms were collected and used to define the orthodromic response. The action of iontophoretically applied luteinizing hormone-releasing hormone (LHRH) and an LHRH fragment, Ac-LHRH5-10, on the activity of orthodromically responsive neurons was tested. Of a total of 187 neurons recorded, 119 were identified as orthodromically responsive. Three types of orthodromic responses were observed: excitatory, inhibitory, and complex. Priming the animals with 5 micrograms estradiol benzoate (EB) 48 hr prior to recording had no effect on the overall number of neurons responding to septal area stimulation, but EB priming did significantly reduce the percentage of orthodromically excited neurons. The firing rate of the majority of amygdala neurons responsive to septal area stimulation was not affected by iontophoretically applied LHRH (59 of 76) or LHRH fragment (41 of 65). In some cases, application of LHRH (10 of 76) or Ac-LHRH5-10 (12 of 55) produced a change in neuronal firing that was similar in direction to the orthodromically evoked response. When applied during the collection of peristimulus time histograms, both peptides were also able to modulate the orthodromically evoked response (five of 18 cells tested with LHRH and three of 14 cells tested with Ac-LHRH5 10). The results demonstrate a large projection from the septal area to the amygdala, one component of which is altered by estrogen priming.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237780 TI - Autoradiographic localization of cocaine binding sites by [3H]CFT ([3H]WIN 35,428) in the monkey brain. AB - The cocaine analog [3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane ([3H]CFT or [3H]WIN 35,428 binds with high affinity and selectivity to cocaine receptors in the monkey caudate-putamen. [3H]CFT was used to map the regional distribution of cocaine binding sites in slide-mounted sections of monkey brains using autoradiographic techniques. Hemicoronal brain sections were incubated with [3H]CFT (3 nM) alone or in the presence of excess (-)-cocaine (30 microM) to mask the binding sites. High densities of [3H]CFT binding sites were detected in the caudate nucleus, putamen, and nucleus accumbens. In all three regions, binding was markedly reduced by coincubation with unlabeled (-)-cocaine, indicating low levels of nonspecific binding. Little or no binding was observed in the cortex, thalamus, globus pallidus, or white matter tracts at the levels studied. In order to characterize binding sites for [3H]CFT in tissue sections, competition experiments were conducted using a fixed concentration of [3H]CFT (3 nM) and a range of concentrations of (-)-cocaine, (+)-cocaine, CFT, Lu 19-005, GBR 12909, bupropion, and citalopram. The IC50 values for the drugs in tissue sections corresponded closely with their reported IC50 values in monkey caudate-putamen membranes (r = 0.99, p less than 0.001), suggesting that [3H]CFT binding is similar in the two preparations. These findings support the view that cocaine receptors labeled by [3H]CFT are localized predominantly in dopamine-rich brain regions implicated in the behavioral effects and abuse of cocaine. PMID- 2237781 TI - Electrosensory systems in fish. AB - A close integration of behavioral, neurophysiological, and neuroanatomical approaches has guided research on the neural basis of electrosensation and the generation of behaviors associated with this modality. By postulating neuronal implementations of specific computations in sensory information processing, behavioral studies have been crucial in focusing studies at the neuronal level onto behaviorally relevant structural and functional aspects. Physiological and anatomical studies have analyzed a) neural networks underlying the distributed processing of sensory information, b) the role of descending recurrent pathways and efference copy mechanisms for the filtering of incoming information, c) the significance of multiple topographic representations for sensory information processing, and d) the modulation of sensory and motor structures through various transmitters and receptor subtypes. Developmental studies have explored the significance of steroid hormones for the tuning of electroreceptors to the frequency of an endogenous neuronal oscillator which drives the electric current pulses necessary for their stimulation. Embryological studies have revealed that the development of mechanoreceptors and electroreceptors in the fish's skin is induced by the innervation of primary afferent nerve fibers which are specific with regard to their central connections as well as with regard to the type of receptor induced in the periphery. PMID- 2237782 TI - Analysis of a multiple-contact synapse missing a normally obligatory postsynaptic neuron: an electron microscopic study in the compound eye of Musca domestica. AB - In the compound eye of the adult female fly Musca domestica, photoreceptors form populations of multiple-contact output synapses, stereotypic in their architecture and in the identity of the four postsynaptic elements. Two postsynaptic elements, always originating from monopolar interneurons L1 and L2, lie side by side beneath the elongated presynaptic bar. Beneath each end of the bar, a further postsynaptic contact is located. These contacts most often are two processes either of amacrine cells or of epithelial glial cells. Monopolar cell L3 may be postsynaptic as well, with either an amacrine or a glial process completing the tetrad. To learn more about the factors determining connectivity and synaptic architecture, a three-dimensional reconstruction of serial electron microscopic sections was used to analyze a population of photoreceptor synapses at which one of the normally obligatory postsynaptic neurons, L1, was missing. In this abnormal case, the synapses make the normal four postsynaptic contacts in only 39% of the cases, otherwise making three (39%) or two (22%) contacts. Specificity of connectivity is preserved faithfully except that beta processes of T1 cells were postsynaptic at 2% of the synapses, where they do not normally contribute. In contrast to normal synapses, where amacrine and glial cell processes are mutual exclusive, such pairings could coexist in the aberrant synapse (27% of all synapses). All postsynaptic cells contributed the normal number of processes to a synaptic site, except for three synapses each with a supernumerary amacrine cell process. The postsynaptic cells therefore may be involved in regulating the number of their contacts made to a synaptic site. PMID- 2237783 TI - Synaptic remodelling of perforated synapses during development and maturation in a visual projection area in birds. AB - Perforated synapses are characterized by the appearance of one or more discontinuities in the postsynaptic density (PSD). These synapses are thought to represent intermediate stages in synaptic remodelling and turnover. To determine the dynamic level of these processes, the development of perforated synapses at different ages was examined in the neuropil of the ectostriatum, a visual projection area in birds. The overall number of perforated synapses per unit volume increases during development. Single and multiple perforated synapses, however, show a different developmental trend. Between 20 and 100 days, when the number of multiple perforated synapses decreases by 46%, single perforated synapses increase by 83% in number per unit volume. No significant changes in single or multiple perforated synapses can be observed at younger ages (i.e., 5 or 10 days). Various parameters increase between 10 and 20 days, followed by a reduction at 100 days: The relative frequency of perforations per synaptic contact, the length of the postsynaptic density including the size of the perforation, the length of the synaptic contact zone in perforated synapses excluding the size of the perforation, and the size of the perforation follow the same trend. PMID- 2237784 TI - Long-term synaptic potentiation in the amygdala. AB - The manner in which the circuitry of the amygdala computes its suspected mnemonic functions has been a mystery, partly because the cytoarchitectual complexity of this nuclear group has impeded the necessary cellular analysis. Here we report in vitro methods and results that may help elucidate cellular learning mechanisms in amygdala neurons. The amygdala brain slice preparation was combined with the single-electrode clamp (SEC) technique for intracellular analysis of membrane properties and synaptic responses. With respect to the active and passive membrane properties, we found considerable diversity among the population of cells that were sampled in the lateral and basolateral nuclei (n = 85). Synaptic inputs to these neurons were studied by stimulating the external capsule (EC), which was shown to produce a complex response that typically consisted of an excitatory followed by an inhibitory component. Based on several criteria, the excitatory component appeared to reflect a monosynaptic connection from the EC. One immediate goal was to discover whether the excitatory component displays the phenomenon of long-term potentiation (LTP)--a persistent increase in synaptic strength that can be induced by brief periods of the appropriate synaptic stimulation. Indeed, we found that high-frequency (100 Hz) stimulation of the EC induced LTP in 80% of the cells from which suitable recordings were obtained (n = 20). This finding of LTP in the amygdala is significant in regard to current efforts to explore linkages between this use-dependent form of synaptic plasticity and rapid kinds of associative learning. PMID- 2237786 TI - [We did the right thing. Faeroe's hospital on a starvation diet]. PMID- 2237785 TI - Identification of a subpopulation of neuropeptide Y-containing locus coeruleus neurons that project to the entorhinal cortex. AB - A fundamental question important to the understanding of the neurochemical organization of the central nervous system focuses on the relationships between the differential phenotypic expression of multiple neurotransmitter markers in individual neuronal populations and the factors that regulate their expression. The first approach in studying this phenomenon is the determination of specific relationships between neurochemically distinct neuronal subpopulations and their efferent targets. The pontine nucleus locus coeruleus (LC) provides a useful model for addressing this question since the projections of LC neurons are topographically organized and several neuropeptides are expressed along with noradrenergic markers in subsets of these neurons. In these studies, we have focused on defining the efferent targets of LC neurons that contain neuropeptide tyrosine (NPY)-like immunoreactivity. This has been accomplished by injecting the retrograde fluorescent tracer fluorogold into specific cortical and hippocampal targets in adult rats and identifying the proportion of retrogradely labeled LC neurons that are positive for NPY-like immunoreactivity. In agreement with other investigators, no preferential cortical projections of NPY-positive LC neurons were observed. However, when fluorogold injections included or were limited to the entorhinal cortex, a discrete cluster of round or ovoid neurons in the dorsomedial portion of the LC approximately 9.8 mm posterior to bregma were found to contain NPY-like immunoreactivity. This observation demonstrates that some topographic organization of NPY-containing LC neurons does exist. In fact, these data indicate that morphologic and topographic organization exists even within neurochemically distinct subsets of neuronal populations. PMID- 2237787 TI - [Barricades]. PMID- 2237788 TI - [Breast cancer. Drawing lots with powerless research personnel]. PMID- 2237789 TI - [Holitis and a pain in the paradigms]. PMID- 2237790 TI - [Livsdraben. Interview by Teddy Osterlin Koch]. PMID- 2237791 TI - [Next to a miracle]. PMID- 2237792 TI - [A transfusion of love]. PMID- 2237793 TI - [Fantasy as a tool]. PMID- 2237794 TI - [The system-preserving stopper]. PMID- 2237795 TI - [Professional nursing guidance. Teacher, teacher, teacher]. PMID- 2237796 TI - [Professional nursing guidance. Help for isolated nurses]. PMID- 2237797 TI - [Death criteria. Legislation on autopsy and transplantation]. PMID- 2237798 TI - [Award-winning new building is shameless]. PMID- 2237799 TI - [Work time--37 hours = 5 X 7 hours and 24 minutes]. PMID- 2237800 TI - [Important questions are still unanswered]. PMID- 2237801 TI - [Funen was fine]. PMID- 2237802 TI - [Psychiatric nursing. The face of force]. PMID- 2237803 TI - [Pension Fund]. PMID- 2237804 TI - [Madonna in crisis]. PMID- 2237805 TI - [Primary health care. An end to records]. PMID- 2237806 TI - [Health education. Health for sale]. PMID- 2237807 TI - [Work environment. Violence is not a private affair]. PMID- 2237808 TI - [Education. Sweet Suzie picks up the fight with Florence]. PMID- 2237809 TI - [Work environment. Patients get all the psychological care]. PMID- 2237810 TI - Cellular-phase fibrinolysis and coronary reperfusion during acute myocardial infarction: a study in patients receiving intravenous streptokinase methylprednisolone therapy. AB - Activation of plasma plasminogen to plasmin is the objective of current strategies for thrombolytic therapy. Although thrombolytic activity in blood involves a large cellular component as well as that in plasma, the contribution of this cellular phase to clinical thrombolysis has not been examined. Using a 125I-fibrin test tube assay, we determined blood, plasma and calculated cellular phase fibrinolytic activities in 39 patients with acute myocardial infarction before, immediately after, and at 2 hours after therapy with an intravenous streptokinase-methylprednisolone regimen. By coronary angiography and time to peak creatine phosphokinase levels, 32 patients had coronary reperfusion and 7 did not. Before streptokinase therapy, cellular phase activity of patients who reperfused was more than 2-fold greater than that of patients who did not reperfuse (p less than 0.001), while plasma activities were identical, suggesting that intrinsic cellular phase activity may be a determinant of the success of subsequent thrombolytic therapy. In both groups, in addition to the expected (and similar) increases in plasma activity, cellular phase activity increased when compared with pre-treatment values (+96% to +248%; p less than 0.001), with accompanying increase in blood granulocyte count (+23% to +65%), indicating that blood cells, as well as plasma, are major contributors to streptokinase-mediated fibrinolysis. Cellular phase stimulation was reproduced in a patient receiving streptokinase without methylprednisolone, and by addition of streptokinase to normal blood in vitro, indicating that streptokinase alone could account for these effects. Increased cellular phase activity in patients who reperfused after streptokinase was similar to that in those who did not reperfuse, when pre treatment values were considered. These findings indicate that initial cellular phase activity in blood may determine subsequent fibrinolytic response, and that there is a significant cellular phase component to the fibrinolytic response to streptokinase, probably mediated by increased numbers of blood neutrophils, with a possible contribution from increased activity of individual neutrophils. PMID- 2237811 TI - Platelet von Willebrand factor assay: results using two methods for platelet lysis. AB - Two different methods (using Triton X-100 and glycerol) for lysing platelets to measure platelet vWF concentrations were compared directly. The platelet concentration of von Willebrand factor antigen (vWF:Ag) was similar for both methods, whereas ristocetin cofactor activity (Ricof) was higher with Triton than with glycerol. After storing platelet lysates for two months at -80 degrees C vWF:Ag and Ricof concentrations decreased with both methods of lysis. Larger than normal (supranormal) vWF multimeric forms could be visualized in platelet lysates obtained using both methods, with no change of the multimeric pattern during storage. Triton can be recommended as the agent of choice to lyse platelets for measurement of their vWF concentration, but the samples must be assayed within two weeks to avoid decay of Ricof activity. PMID- 2237812 TI - d-Indobufen inhibits collagen-induced intracellular calcium mobilization and inositol phosphates formation in human platelets. AB - We obtained evidence that the cyclooxygenase inhibitor d-indobufen, (+)2[p-(1-oxo 2-isoindolinyl)phenyl] buthylic acid has a potent and specific inhibitory effect on collagen-induced aggregation and 40K-protein phosphorylation (Mamiya, S., Hagiwara, M., Ishikawa, T., and Hidaka, H. Thromb. Res. 54, 447, 1989). In Fura-2 loaded platelets, d-indobufen inhibited collagen-induced intracellular calcium mobilization in a dose dependent manner and this inhibitory effect on calcium mobilization paralleled that on aggregation, either in the presence or absence of extracellular free calcium ions. This compound inhibited inositol phosphates (IPs) formation in collagen-stimulated platelets. In arachidonic acid-stimulated platelets, d-indobufen caused a lag on calcium mobilization, as observed with arachidonic acid-induced aggregation. There was no significant effect on thrombin or A23187-induced calcium mobilization or on aggregation. These observations suggest that the collagen receptor couples to a distinct intracellular calcium mobilization system possibly via inositol phospholipid metabolism and that d indobufen blocks the collagen-induced aggregation by arresting mobilization of intracellular calcium. PMID- 2237813 TI - Fibrinogen-containing membrane-associated structures arising at the surfaces of ADP-stimulated blood platelets. AB - Ultrastructural studies of ADP-stimulated gel-filtered human platelets incubated with different concentrations of fibrinogen reveal unusual extracellular structures composed at least partly of the aggregated fibrinogen. Development of these structures depends on the exogenous fibrinogen concentration and duration of the incubation. Fibrinogen-containing extracellular material exists in two different structural forms. As was shown earlier, one of them is represented by dense, amorphous intercellular matrix and is localized mainly in platelet microaggregates (Belitser et al., Thromb. Res., in press). Another one consists of huge sheet-like structures bearing individual or clumped platelets bound either to one or to both of their surfaces. After thrombin treatment, these structures could not be found anymore; sometimes they seem to be substituted by the fibrin-like fibers spatially connected to each other and/or to the platelet membranes. It has been suggested that soluble fibrinogen interacting with its specific membrane receptors undergoes conformational changes promoting intermolecular interactions and resulting in the fibrinogen aggregates formation at the surfaces of the activated platelets. A probable physiological significance of the structures described is discussed. It is supposed that under certain conditions in vivo they may play an important role, in particular as a highly concentrated substrate for the thrombin action, providing in such a way a possibility of rapid, effective consolidation of the initial platelet thrombi with the fibrin fibers. PMID- 2237814 TI - Lack of cross-reactivity between anticardiolipin antibodies and glycosaminoglycans. PMID- 2237815 TI - Phast assessment of vWf:Ag multimeric distribution. PMID- 2237816 TI - The hirudin standard. PMID- 2237817 TI - Antithrombin III activity in Chinese women with preeclampsia. PMID- 2237818 TI - Effect of endothelial cells on platelet aggregation in platelet rich plasma (PRP) and whole blood. PMID- 2237819 TI - Bilirubin induces platelet aggregation. PMID- 2237820 TI - Localization of human tissue factor antigen by immunostaining with monospecific, polyclonal anti-human tissue factor antibody. AB - Tissue factor, the cofactor for factor VIIa-catalyzed activation of factors IX and X, plays an important role in the initiation of hemostasis. However, the distribution of tissue factor in the body has not been defined until recently. In the present study frozen sections of non-malignant human tissues were immunostained using polyclonal, monospecific rabbit anti-human tissue factor antibodies. Specificity of the anti-tissue factor antibody was established by Western blotting. Sensitivity of the immunostaining technique for tissue factor antigen was confirmed by correlating staining of non-perturbed and perturbed cultured human umbilical vein endothelial cells with their surface membrane tissue factor coagulant activity. Brain, lung and placenta, all known to possess large amounts of tissue factor procoagulant activity, stained strongly for tissue factor, as did peripheral nerves and autonomic ganglia. Epithelium of skin, mucosa, and glomeruli also stained; however, epithelium lining excretory ducts failed to stain. Skeletal muscle did not stain, but cardiac muscle stained faintly. Smooth muscle also did not stain except for the muscularis mucosa of the esophagus, which stained brightly. Fibroblasts varied in stainability; those found in the adventitia of vessels stained strongly. The endothelium, tunica intima and tunica media of blood vessels consistently failed to stain. The distribution of tissue factor antigen as demonstrated by immunostaining supports the hypothesis that maintenance of a physical barrier between tissue factor activity and blood is key to the normal regulation of hemostasis. PMID- 2237821 TI - Modifications of biological activities of heparin and fraxiparine induced by the size and the age of a thrombus. Experimental study. AB - Heparin and its fractions have often been tested on fresh experimental thrombosis. However in human clinic, drugs are administered not on fresh, but rather on old constituted thrombi. In order to evaluate the effects of antithrombotic agents in these conditions, both drugs (unfractionated heparin and Fraxiparine) were administered on 150 rats at different times and so, could take effect on thrombi with different ages. Heparin was more active as its fraction on fresh thrombi (2 hours old), but no more effects could be observed for all drugs when the thrombus was 52 hours old. Biological activities (A.P.T.T., anti-IIa and anti-Xa activities) decreased as the thrombi increased in weight and age. PMID- 2237822 TI - A new competitive binding enzyme-linked immunosorbent assay for glycocalicin in plasma and platelet concentrate supernatants. AB - A new competitive binding enzyme-linked immunosorbent assay (CB ELISA) for glycocalicin (GC) was developed using GC coated wells and a monoclonal antibody (MAb) to glycoprotein Ib (AN51). The principal stages of the CB ELISA consisted of coating the plate with GC extract overnight, blocking with 3% BSA, incubating the wells with test or standard sample dilution and AN51, and a final incubation with horseradish peroxidase-conjugated goat anti-mouse IgG. Serial dilutions of purified GC, starting in 2% BSA, yielded standard curves which were linear between 10 and 0.4 micrograms/ml. Parallel curves were obtained for platelet concentrate supernatants and for citrated plasma. We used the ELISA to measure GC levels in platelet concentrates during storage. The results indicated that soluble GC increased progressively during storage from 3.3 to 6.7 micrograms/ml, while GC levels in platelet-poor plasma remained at 1.9-2.2 micrograms/ml. These results show that the new CB ELISA is a simple and short assay for the direct measurement of GC in plasma solutions, and may be of use in clinical studies. PMID- 2237823 TI - Collagen-platelet interaction: type XI collagen-induced platelet aggregation. AB - Type XI collagen in its native fibrillar but not in soluble monomeric form mediates human platelet aggregation and release of adenosine triphosphate in a dose-dependent manner. Its action is inhibited by aspirin. Type XI collagen also increased radiolabelled phosphate incorporation into protein bands with molecular weights of 42 KDa and 22 KDa, respectively. In contract, these events were not observed in platelets incubated with type IX collagen. These results suggest that the fibrillar type XI collagen has the same ability as other types of collagen to induce human platelet aggregation. PMID- 2237824 TI - Ability of high-affinity heparin fractions with decreasing affinity for antithrombin III to activate ATIII isoforms. AB - Previous studies investigated the effect of heparin fractions on the rates of thrombin inhibition by naturally occurring antithrombin III (ATIII) isoforms differing in affinity for heparin. Heparin with low-affinity for ATIII increased the rate of thrombin inhibition by the higher affinity isoform about 10-fold more effectively than by the other isoform. This paper reports on the effect of a series of high-affinity heparin fractions with decreasing affinity for ATIII. As affinity decreased, the ability of the heparin fractions to increase the rate of the ATIII-thrombin reactions decreased, and these fractions slightly more effectively increased the rate of thrombin inhibition by the higher-affinity ATIII isoform. The effect of the heparin fractions on the ATIII-factor Xa reactions was also investigated. The activity of the fractions in this reaction also showed a dependence on ATIII-affinity. Studies on the competition of isoforms for immobilized heparin showed that the isoform with higher affinity for ATIII effectively competes with its congener for binding to heparin. The results indicate that heterogeneity in high-affinity heparin results in heterogeneity in affinity for ATIII that is significantly correlated with the ability of the heparin to potentiate ATIII-protease reactions. In spite of about equal activation of the ATIII isoforms by high-affinity heparin, the importance of the higher-affinity isoform is indicated by its ability to compete effectively for these heparin species. PMID- 2237825 TI - Effects of calcium channel blockers on platelet aggregation and thromboxane A2 formation: an in vivo double blind randomized study. AB - In this double blind cross over study against placebo the in vivo effects of diltiazem, nifedipine and verapamil on platelet aggregation and Thromboxane A2 (TxA2) formation were evaluated in eighteen healthy adults. No significant inhibition of platelet aggregation or TxA2 formation was found either after acute or short term (8 days) administration of the three calcium channel blockers at the usual therapeutical dosages. Our study indicate that diltiazem, nifedipine and verapamil are unable to significantly affect platelet aggregation and TxA2 formation in healthy subjects. PMID- 2237826 TI - Thrombin generation in prothrombin-complex-preparations; its effect on a chromogenic substrate, fibrinogen and platelets. AB - The kinetics of thrombin generation in various prothrombin-complex-preparations (PCC) were investigated using a chromogenic substrate assay. The rate of thrombin formation and the total activity of thrombin generated varied considerably among different preparations. The thrombin generation velocity influenced the rate of fibrinogen to fibrin conversion, measured as plasma viscosity alteration per unit of time. It also influenced thrombin induced platelet aggregation with regard to maximum aggregation and aggregation velocity. The kinetic parameters measured photometrically and coagulometrically showed reduced generation velocities and less thrombin effects with thrombin formed in PCCs than with thrombin generated in plasma. The quantitative differences between thrombin effects in various PCCs on platelet aggregation did not correlate with the data of the amidolytic and fibrinogenolytic measurements. The significance of the results is discussed with regard to the question of whether, or to what extent, PCCs could cause or accelerate a disseminated intravascular coagulation. PMID- 2237827 TI - Platelet-reactive sites in human collagens I and III: evidence for cell recognition sites in collagen unrelated to RGD and like sequences. AB - Following fragmentation of the collagen molecule with cyanogen bromide (CB), two major platelet-aggregatory sites were detected with human platelets in the alpha 1(I)-chain of human collagen I corresponding to those detected previously in bovine alpha 1(I)-chains. Two main sites were also detected in the human alpha 1(III)-chain, at locations different from those in the alpha 1(I)-chain. Only one of these had been previously recognised. The new site was found in the peptide alpha 1(III)CB3, the amino acid sequence of which does not contain the cell recognition site RGD nor comparable sequences that might be supposed to serve this function such as KGD, RGE or KGE. The peptide does, however, contain the sequence GRPGRPGER which reflects a spacing of basic residues (at positions 2 and 9) we have previously postulated to be essential for collagen to cause platelet aggregation. None of the CB-derived peptides was able to cause an aggregation of rabbit platelets. Human platelet secretion, as aggregation, was only induced by CB-derived fragments in triple-helical, polymeric form. One fragment, peptide alpha 1(III)CB8, was able to induce secretion although lacking aggregatory activity. Platelet adhesion occurred to all of the fragments, including those lacking aggregatory activity. Adhesion also occurred to the collagen-like polypeptide (PGP) n. However, inhibition studies suggested that the GPP sequence which occurs frequently along the length of the collagen molecule is not responsible for platelet adhesion to collagen. PMID- 2237828 TI - Production of plasminogen activator and plasminogen activator inhibitor by bovine lymphatic endothelial cells: modulation by TNF-alpha. AB - We have investigated whether lymphatic endothelial cells in culture produce plasminogen activators (PAs) and their inhibitors (PAIs) and if these activities can be modulated by the inflammatory cytokine Tumor Necrosis Factor alpha (TNF alpha). Examination by reverse fibrin autography of the conditioned medium from these cells revealed a PAI of Mr 50 kDa. Also evident by fibrin autography were two species of PAs, of Mr 110 kDa and Mr 60 kDa. The 110 kDa protein co-migrated with the PA-PAI complexes and the 60 kDa protein co-migrated with tissue Plasminogen Activator (tPA). Functional and immunological assays indicated the human TNF-alpha increased the type 1 plasminogen activator inhibitor (PAI-1) in a time dependent manner. Treatment of the cells with recombinant human TNF-alpha for 24 hours resulted in a 3 to 7 fold increase in the amount of PAI released into the conditioned media. Immunoblot analysis identified the PAI in the TNF alpha treated cell conditioned media, as PAI-1. Deposition of PAI-1 in the extracellular matrix then became apparent. TNF-alpha increased 4 fold the amount of tPA-PAI-1 complexes (Mr 110 kDa) detected in the conditioned media. Free tPA (Mr 60 kDa) decreased to 1/5 of control. Net fibrinolytic activity, as determined by a chromogenic substrate assay, decreased after TNF-alpha treatment. No urokinase type Plasminogen Activator (uPA) activity was detected in control or treated cells. This fibrinolytic activity may be important in maintaining free fluid movement in the interstitium and lymphatic vessels and in inflammatory states this potential may be decreased by the increase in PAI-1. PMID- 2237829 TI - Qualitative and quantitative abnormalities of von Willebrand antigen in patients with diabetes mellitus. AB - Previous reported studies of vVWf antigen (vWf:Ag) in patients with diabetes mellitus have not shown qualitative abnormalities despite frequent documentation of raised vWf:Ag. Twenty two patients with established diabetes mellitus have been studied and qualitative abnormalities of vWf:Ag multimers were found in 10 patients who had poorer glycaemic control (as judged by plasma fructosamine) than the other 12 patients. Seven of the 22 patients were restudied after a 3 month period of improved glycaemic control and the vWf:Ag multimer abnormalities disappeared in 6 of these. Some of the structural abnormalities were accompanied by loss of vWf functional activity. As vWf:Ag is synthesised in the endothelial cell, vWf:Ag abnormalities during periods of poor glycaemic control may reflect endothelial cell damage with vWf:Ag release and possibly subsequent proteolysis. PMID- 2237830 TI - Effect of dietary canola and reference oils upon serum lipids and platelet aggregation. AB - To compare Canola a terrestrial (n-3) oil with fish oil (n-3) and common vegetable oil (n-6) in decreasing serum lipids and platelet aggregation, various oils were included in Chow-based diets and fed to rats in an eight-weeks feeding trial. The Chow diet contained 2% cholesterol along with either Canola, menhaden, safflower, or partially hydrogenated soy oil, or no oil addendum. The menhaden oil group was the only one to show a significant reduction in serum cholesterol and triglycerides and at the same time yielded the most uniform decrease in platelet aggregability. However, this same group was also the only one to show a decrease in serum tocopherol levels, suggesting that improving an atherogenic risk profile may require antioxidant supplementation. In these rat trials, Canola oil supplementation did not yield the same results measured during menhaden supplementation. PMID- 2237831 TI - Interference of levamisole with Forssman shock. AB - The anti-helminthic drug levamisole has been used as an adjunct in the treatment of some immunologic defects including cancer. Recently, it has been shown that this drug inhibits thromboxane synthetase as well. Since Forssman shock in guinea pig is used as a model for pulmonary thromboembolism involving thromboxane A2, we studied the interference of levamisole with bronchoconstriction, thrombocytopenia, endothelial cells and pulmonary damage induced by Forssman antiserum. Levamisole inhibited dose-dependently the pathological changes produced by Forssman antiserum raising the possibility that levamisole may be effective for the treatment of pulmonary thromboembolism in man. PMID- 2237832 TI - Release of extrinsic pathway inhibitor after heparin injection: increased response in cancer patients. PMID- 2237833 TI - Binding properties of hirudin determined by gel filtration and gel electrophoresis. PMID- 2237834 TI - Antiphospholipid antibodies detected as anticephalin and anticardiolipin antibodies in patients with acute myocardial infarction: immunological response to myocardial necrosis? PMID- 2237835 TI - Histidine-rich glycoprotein levels in children: the effect of age. PMID- 2237836 TI - Discrepancies between clotting and amidolytic assay in congenital clotting disorders. PMID- 2237837 TI - Effect of 1-desamino-8-D-arginine vasopressin (DDAVP) on human platelets. AB - Intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP), an analog of arginine vasopressin (AVP), results in a rise in plasma levels of factor VIII coagulant activity and the von Willebrand factor. DDAVP infusion has been shown to shorten the prolonged bleeding time of patients with inherited platelet defects but the mechanism for this has not been fully clarified. There is little information available on the direct effect of DDAVP on platelets. We examined the effect of DDAVP on platelet responses, including Ca2+ mobilization, to understand the mechanisms by which DDAVP shortens the bleeding time in patients with primary platelet defects. In normal human platelets, DDAVP alone upto 100 microM did not induce aggregation, secretion or a rise in the intracellular Ca2+ concentration, monitored using quin2. In contrast AVP induced all three responses in a dose dependent manner. Interestingly preincubation of platelets with DDAVP at a 100 fold greater concentration inhibited the responses to AVP indicating that DDAVP does interact with the platelets. Moreover, DDAVP did not either potentiate or inhibit the responses to thrombin or ADP. These studies indicate that it is unlikely that the beneficial effect of DDAVP in patients with primary platelet defects is related to a direct stimulatory effect on platelets. PMID- 2237839 TI - Conformational differences between latent and active plasminogen activator inhibitor, PAI-1: a spectroscopic study. AB - The protein conformation of latent and active PAI-1 has been studied with circular dichroism, absorbance and fluorescence spectroscopy. The far ultraviolet circular dichroism spectrum of latent PAI-1 displays a more negative band at 220 nm than active PAI-1, crossing the baseline at a lower wavelength. Active PAI-1 shows an absorption maximum at lower wavelength (269 nm) than present in latent PAI-1 (278 nm). In consistency, slow denaturation of active PAI-1 by incubation for two hours at 37 degrees C induces a shift in the absorption maximum from 268 nm to 274 nm. The fluorescence emission maximum of latent PAI-1 is at lower wavelength (335 nm) than that of active PAI-1 (340 nm). These spectroscopic differences are interpreted as reflecting a more tight conformation, with the tryptophan residues in a more apolar environment, in latent PAI-1 compared to active PAI-1. PMID- 2237838 TI - Selective effects of dietary fats on vascular 13-HODE synthesis and platelet/vessel wall interactions. AB - Fish oil (FO) diets are associated with decreased thrombosis, which is though to be related, in part, to changes in platelet and vessel wall prostanoid synthesis. Recently, we found that 13-hydroxyoctadecadienoic acid (13-HODE) synthesized in the vessel wall from linoleic acid (LA, 18:2 n-6) via the lipoxygenase pathway, also decreases platelet/vessel wall interactions. Thus, we determined whether diets containing fish oil, walnut oil (rich in linoleic acid), black currant seed oil (rich in both linoleic and gamma linolenic acids, 18:3 n-6), or lard influenced vessel wall 13-HODE synthesis and platelet/vessel wall adhesion in rabbits. In vivo, vessel wall thrombogenicity was decreased in animals fed the black currant seed oil rich diet for 4 weeks as compared to the control "LARD" diet. This latter effect was better obtained when gamma linoleic acid was present suggesting a secondary effect of this fatty acid. The decreased vessel wall thrombogenicity in those animals, was associated with increased vessel wall 13 HODE synthesis. In contrast, ex vivo platelet adhesivity was significantly decreased in the fish oil diet fed animals, as compared to the control "LARD" diet and correlated with decreased platelet 12-HETE synthesis. We conclude that both fish oil and black currant seed oil rich diets inhibit platelet/vessel wall adhesion; the black current seed oil diet by increasing the availability of linoleic acid for 13-HODE synthesis and inhibiting vessel wall thrombogenicity; the fish oil diet, by inhibiting platelet 12-HETE synthesis and subsequent platelet adhesion. PMID- 2237840 TI - Fibrinolysis as a feature of disseminated intravascular coagulation (DIC) after Pseudonaja textilis textilis envenomation. AB - Blood was obtained from four patients envenomated by the Australian common brown snake, Pseudonaja textilis textilis. This elapid snake has one of the most toxic venoms in the world, containing extremely potent neurotoxic and coagulant components. The latter is a potent complete prothrombinase, converting prothrombin to alpha-thrombin, and comprises more than 30% of the total venom protein. The four envenomated patients developed a typical consumption coagulopathy. Serial serum and plasma samples from patients were studied by immunoaffinity adsorption, 2-alanine precipitation of fibrinogen and fibrinogen related products and 2-dimensional immunoelectrophoresis, and assayed for crosslinked fibrin degradation products as D dimer, using the monoclonal antibody, DD-3B6/22. These procedures showed the virtually complete disappearance of fibrinogen, accompanied by the appearance of large quantities of fibrinogen and fibrin degradation products consisting of both crosslinked and noncrosslinked species. With recovery, a homogeneous high molecular weight fibrinogen was observed. The data suggest that the prothrombin activator of this venom causes the generation of thrombin which subsequently converts fibrinogen to fibrin and stimulates partial crosslinking of both alpha and gamma-chains. The resultant disseminated intravascular coagulation is accompanied by very active secondary fibrinolysis which apparently limits the extent of any microvascular thrombosis but which may contribute to a bleeding tendency. PMID- 2237841 TI - Thrombin activity in pulmonary emboli obtained at autopsy. PMID- 2237842 TI - A comparison of different reagents for the activated partial thromboplastin time in rabbit and rat plasma. PMID- 2237843 TI - [The sexual debut of Norwegian youth]. PMID- 2237844 TI - [What quality assurance are we to demand for diagnosis and treatment of gastrointestinal cancer in Norway during the 1990's?]. PMID- 2237845 TI - [Study and diagnosis of pancreatic cancer]. AB - The most common initial symptom was abdominal pain. Other frequent debut symptoms were loss of weight and jaundice. ERCP and PTC were found to be the best diagnostic procedures. CT or ultrasonography were normal in 10-20% of the patients. Nearly all tumors of the pancreas were found by the ERCP procedure. We also used angiography to evaluate operability of the pancreas tumor. Angiography was found to be a very uncertain diagnostic procedure, however, and we have now decided not to use angiography in the future evaluation of patients with cancer of the pancreas. PMID- 2237846 TI - [Cancer of the pancreatic head and the periampullary region]. AB - Between 1976 and 1988, 16 patients underwent a Whipple resection or total pancreatectomy for carcinoma of the head of the pancreas, the ampulla of Vater or the distal common bile duct. Nine patients had carcinoma of the pancreas. Two of these patients are long-term survivors. The tumors in these patients were highly differentiated and localized close to the common bile duct. Four had ampullary lesions, and are all alive today. Three patients had carcinoma of the common bile duct. One of these patients is alive. PMID- 2237847 TI - [Views on simple surgical aspects of gastrointestinal cancer in Norway]. AB - A questionnaire was used to study various aspects of the surgical treatment of cancer of the oesophagus, pancreas, stomach and colon/rectum in Norway. 48 of 51 departments replied. Half of the departments perform radical operations for oesophageal cancer and nearly all do total gastrectomies and low anterior resections for rectal cancer. Palliative surgery is seldom performed for oesophageal cancer, but is frequently performed for gastric cancer. Obstruction of the colon is relieved preferably by primary resection. Low anterior resection is usually performed when a free resection margin of 2 cm can be achieved. Jaundice is relieved palliatively preferably by endoscopy. University hospitals perform total gastrectomy to a greater extent than other hospital and have greater faith in radical operations for pancreatic cancer. Otherwise there are no conspicuous differences of opinion between the different categories of hospitals. PMID- 2237848 TI - [Abdominal injuries after blunt trauma]. AB - We present a series of 331 patients admitted to hospital in 1980-87 with abdominal injuries after blunt trauma. The patients included 230 males and 101 females. The median age was 29 years. More than half of the patients were injured in traffic accidents. 11% were transferred to our Trauma Center from other hospitals, median five hours after the accident. A doctor-manned helicopter transported 52 patients (18%) directly to our hospital. 70% had extra-abdominal injuries as well. A minimum of 20% were intoxicated by alcohol and/or drugs. Severe injuries (AIS greater than 3) were present in 46%. 168 patients underwent laparotomy, in 56% within two hours of admission. In 27 of the 168 laparotomized patients (16%) no intraabdominal injury was encountered that needed repair. PMID- 2237849 TI - [Reconstructive surge of blunt renal trauma]. AB - The most usual causes of blunt renal injuries are motor vehicle accidents, falls and participation in contact sports. Severe injuries are rare and a conservative approach in the treatment of such injuries is advocated by most authors. In this article we present a patient who suffered a major injury to the right kidney which was treated successfully by reconstructive surgery. We discuss the diagnosis of renal injuries, indications for surgery and surgical technique. PMID- 2237850 TI - [Infantile hypertrophic pyloric stenosis]. AB - We present 40 patients operated consecutively for pyloric stenosis during an 8 year period (1981-88). The most common symptom was projectile vomiting, which occurred in 92.5% of the cases. On examination only three patients had a palpable hypertrophic pylorus. In 39 patients, a preoperative x-ray examination with contrast was necessary to confirm the diagnosis. A pyleromyotomy was performed in all patients. We discuss the diagnostic routines and the results of our treatment. PMID- 2237851 TI - [Ischemic left ventricular failure. Main stem coronary stenosis treated with angioplasty]. AB - We describe a patient with stenosis on the left main stem and severe impairment of the left ventricular function. Because of reversible myocardial ischaemia in a patient whose clinical situation prohibited surgery, angioplasty on the left main stem was performed, leading to considerable improvement of the ventricular function. Improvement was slow, however, probably due to "stunning" of the myocardium. We underline the importance of early angiography in patients when it is suspected that a larger part of the myocardium is affected by severe, reversible ischaemia. PMID- 2237853 TI - [Acetylsalicylic acid in the prevention of arterial thrombosis. Dosage problems in general and in the authors' experiment]. AB - Acetylsalicylic acid is now accepted as a clinically useful drug for secondary prophylaxis against several thromboembolic complications, but there is still much controversy about the dosage. We discuss this problem, in the light of data from newly published clinical trials and of results from a pharmacological study performed by ourselves. All in all it seems reasonable to recommend 100-150 mg acetylsalicylic acid per day for prophylaxis after acute myocardial infarction. As for cerebrovascular indications, no clinical data available so far justify a dose reduction below 300 mg. PMID- 2237852 TI - [Organophosphate poisoning]. AB - Three cases of poisoning by organophosphate dimethoate are described and the importance of correct diagnosis and adequate treatment emphasized. Therapy consists of large doses of atropine, to counteract the muscarinic and other effects on the central nervous system, followed by a reactivator (e.g. toxogonin) to reverse muscle weakness (nicotinic effects). PMID- 2237855 TI - [Chylothorax]. AB - A 51 year old man developed chylothorax from a non-Hodgkin lymphoma located in the abdomen. The main causes of chylothorax are trauma and malignant disease. The condition is quite often idiopathic. The treatment is usually a combination of surgical treatment, conservative treatment, high voltage radiation and/or pleurodesis with a sclerosing agent. PMID- 2237854 TI - [Post-splenectomy septicemia]. AB - The spleen is a major component of the immune system and plays an important role in the defence against encapsulated bacteria. It is well recognized that splenectomized patients run increased risk of developing serious invasive bacterial infections, especially post-splenectomy septicaemia caused by pneumococci. Two case reports are used to draw attention to infections in patients without a spleen. The author discusses the indications for the use of pneumococcal vaccine, and recommends more extensive use of the vaccine in splenectomized patients in Norway. PMID- 2237856 TI - [Simple spirometry and peak flow measurements]. PMID- 2237857 TI - [The age of sexual debut among Norwegian adolescents]. AB - Kaplan-Meier estimates were used to study age at first intercourse among Norwegian adolescents. The data stemmed from a nation-wide study of 3,000 Norwegian adolescents aged 17-19 years. The response rate was 61.8%. Median age at first intercourse was 17.3 years for girls and 18.0 years for boys. The results indicate that median age at first intercourse has not become lower in Norway since 1975. Age at first intercourse was significantly associated with educational aspirations and frequency of visits to church by respondents and parents. Furthermore, age at first intercourse was significantly associated with smoking behaviour, alcohol consumption, peer affiliation and frequency of visiting a discotheque. These inter-relationships confirm that age at first intercourse is an important indicator of the lifestyle of an individual. Thus, in order to influence the sexual behaviour of adolescents it thus seem appropriate, as a supplement to traditional methods of sex education, to employ health promotion activities which focus on environmental and structural factors. PMID- 2237859 TI - [Ventricular arrhythmias. What can be achieved by drug therapy?]. PMID- 2237858 TI - [Hemoglobin, sedimentation and community health legislation. Frequency of tests and fees at the Vaga community health center during 1983-87]. AB - On the basis of laboratory records and doctors' list of appointments, we analyzed the number of hemoglobin tests and sedimentation rates performed at Vaga community health centre during the period 1983-87. In 1983 the doctors worked on a "fee for service" basis. Since 1984 they have been paid a fixed salary. Individual doctors showed little variation in their use of tests, but there were considerable differences between doctors. The average number of tests per patient was stable and seemed independent of how the doctors were reimbursed. PMID- 2237860 TI - [Anticoagulant therapy and cerebral hemorrhage]. PMID- 2237861 TI - [Quality assurance in Norwegian health care]. PMID- 2237862 TI - [Sjogren's syndrome--new aspects]. PMID- 2237863 TI - [Neck distorsions after traffic accidents]. PMID- 2237864 TI - [Facial injuries]. PMID- 2237865 TI - [Osteosynthesis with miniplates in unstable maxillo-zygomatic fractures]. AB - This article discusses the etiology and classification of zygomatic fractures, as well as indications and methods of surgery. Osteosynthesis with a miniplate is a new treatment modality for unstable zygomatic fractures. The operative procedure is relatively simple and gives good cosmetic and functional results. We describe the technique illustrated with pre- and postoperative x-rays of a patient. PMID- 2237866 TI - [Charcot-Marie-Tooth disease. Peroneal muscular atrophy]. AB - The classification of Charcot-Marie-Tooth disease is provisional, because the chromosome and gene localization is still not precisely known, and gene products have not been identified. This article presents an analysis of the clinical, genetical and neurophysiological data of eight Charcot-Marie-Tooth patients. The study was carried out to find out if it is possible to classify the disease from neurophysiological and genetical data. We found Charcot-Marie-Tooth disease transmitted autosomal dominant in three cases, whereas no family pattern was apparent in the remaining five. Among the three cases of autosomal dominant transmission, two were of the segmental demyelinization type, and one had axonal neuropathy. The five patients without a distinct family pattern consisted of three with segmental demyelinization and two with axonal neuropathy. Thus, the neurophysiological subdivision did not correlate with the inheritance, which indicates a genetical heterogeneity for the Charcot-Marie-Tooth disease. PMID- 2237867 TI - [Prognosis of patients with nervous system lesions caused by organic solvents]. AB - 19 patients with chronic organic solvent intoxication of the nervous system were interviewed and examined three years after the diagnosis was set. The study shows a significant reduction of subjective symptoms, especially among the youngest patients. Clinical neurological examination was almost unchanged. 18 of the patients were no longer occupationally exposed to organic solvents. Six patients were still working, and three other patients were being re-educated. Most of the patients were followed by general practitioners. PMID- 2237868 TI - [Epididymis. Anatomy, function and pathology]. AB - Studies on the human epididymis suggest that both histologically and biochemically, it can be subdivided into discrete segments with different functions. Current research attempts to isolate segment-specific secretory markers which can be used in localizing dysfunction and pathology in cases of male infertility. In cases of azoospermia, the segmental level of an occluding lesion also has prognostic relevance for the results of epididymovasostomy. Infection with Chlamydia trachomatis is the most frequent cause of acute epididymitis but an epididymal involvement is also a common feature of chronic prostato-vesiculitis, the etiology of which is unknown. This article provides a short review of the structure and function of the epididymis, the pathological changes in the organ associated with male infertility and the potential methods of treatment. PMID- 2237869 TI - [Intraocular Candida albicans infection]. AB - The article discusses three patients with an intraocular Candida albicans infection. Vitrectomy was performed on two patients in whom the infection occurred after abdominal surgery. Both had significant corpus vitreum involvement. One of these patients regained good visual acuity, while in the other patient preretinal proliferation caused permanently reduced vision. The third patient had only chorioretinal involvement. After intracranial surgery for acusticus neurinoma his general condition deteriorated and he developed septicemia. He was treated with intravenous amphotericin B and visual acuity returned to normal. Early diagnosis and treatment are important for satisfactorily preservation of vision. Therefore patients in risk groups with ocular complaints should be referred immediately to an ophthalmologist. Early diagnostic and therapeutic vitrectomy should be considered for all patients with suspected vitreous involvement. PMID- 2237870 TI - [Treatment of lymphedema in institutions. Two weeks of in-hospital intensive lymphatic drainage followed by maintenance treatment with a pulsator]. AB - 54 patients were admitted to The Norwegian Radium Hospital (hotel ward) for treatment of secondary lymph drainage in the arm or the leg. The treatment consisted of 14 days intensive lymph drainage, including massage and physical exercises, and intermittent compression with pulsator and bandaging. Information/instruction was given continuously. Good elastic stockings were supplied before the patients left the hospital. The treatment was succeeded by a maintenance programme, which the patients carried out themselves at home. The patients were closely followed up and reported on for six months, and were rechecked after another four and 12 months. We present the results after 14 days of intense treatment, followed by a 12-month maintenance programme. PMID- 2237871 TI - [Mesalazine (5-ASA) in ulcerative colitis]. PMID- 2237872 TI - [Written information from hospital to primary physician about discharged patients]. AB - Discharge communications from hospitals to general practitioners in respect of 203 patients have been analyzed in two municipalities in Western Norway. The average interval between discharge from hospital and the first visit to the GP was 25 days (1-198 days). The mean period before arrival of the final report was 28 days (0-175 days). In 38% of the cases the GPs had received no written communication from the hospital upon first contact after discharge. 42% of the preliminary reports and 18% of the final reports were judged to be inadequate. At the first attendance, the GPs were uncertain about the drug regimen in 25% of the cases and about other forms of treatment in 32%. They felt uncertainty about follow-up procedures in the case of 44%. As evaluated by the GPs, in 22% of the cases the absence or inadequacy of the discharge letters might have had a negative influence on the patient's health. A survey of the literature provides a basis for the following recommendations: On leaving the hospital the patient should be given an interim discharge summary containing any information essential for immediate follow-up, to be delivered to the general practitioner by hand. The final discharge letter should focus upon topics of particular interest for the general practitioner: results from clinical examinations and laboratory investigations should be restricted to data necessary for making clinical decisions; treatment given in hospital, including adverse reactions, and drug regimen at discharge; any information on the nature and prognosis of the disease given to the patient and/or relatives during the stay in hospital; evaluation of prognosis and advice on sociomedical rehabilitation in everyday life and at work; a plan for future management of the patient with emphasis on well-defined sharing of tasks and responsibilities between the hospital, the outpatient department and the GP. PMID- 2237873 TI - [The challenge of ecology to medicine]. AB - The science of ecology is an important tool for reflecting upon the interaction between organisms and the environment. However, this science cannot be applied directly to human systems, since human interaction is very complex and is often based on symbolic meanings. An interdisciplinary approach to human ecology is therefore necessary. At a deeper level, ecological thinking might be integrated into a vision of the unity of reality, which includes both subjective and objective experiences, and where human values are just as important as facts. Ecological thinking challenges medicine to take a multidimensional view of man and to regard man, in common with life in general, as a self-organizing system. Value-based ecological thinking should be just as relevant in situations as diverse as our relationship to the individual patient and his community, and our own relationship to the industrial society and our common global environment. PMID- 2237874 TI - [Contraindications for cervix screening]. PMID- 2237875 TI - [Acute pulmonary failure syndrome in adults. New radiologic findings]. PMID- 2237876 TI - [Physicians' continuing and postgraduate education 1991]. PMID- 2237877 TI - [Animal experiments: advice concerning conscientious objections in employment]. PMID- 2237878 TI - [Veterinary Chief Inspection of Public Health. Salmonella studies and especially study for S. enteritidis in Dutch poultry]. PMID- 2237879 TI - [Splenomegaly in stomach torsion]. PMID- 2237880 TI - Metabolic reduction in hypothermia: pathophysiological problems and natural examples--Part 1. AB - Following a description of the protective effects of hypothermia, the limitations resulting from "cold swelling" of the brain, caused by a progressive discrepancy between active and passive cellular transport processes, are discussed. The observation that the tolerable limits of metabolic reduction lie well below the normal turnover rates leads to a short survey of the evolution of energy metabolism. The gradual development of the latter from anaerobiosis to aerobiosis and from poikilothermy to homeothermy apparently provides the background for transient reductions to lower rates which spontaneously occur even in higher vertebrates. As an impressive example of such a natural strategy, the anaerobic survival of diving turtles is outlined which essentially depends on an efficient buffering. This dependence bears analogy to cardioplegia, where an increase in buffering capacity can greatly retard the fall of energy turnover, thus leading, as is shown by microcalorimetry, to an intermediate plateau of anaerobic metabolism. PMID- 2237881 TI - Metabolic reduction in hypothermia: pathophysiological problems and natural examples--Part 2. AB - As an example of spontaneous cooling in homeothermic organisms, hibernation of mammals is described. Based on the fact that all hibernators, at their regulated minimal body temperature, display a uniform turnover rate, related to body weight, the hypothesis is developed that cold tolerance of mammals is generally limited by a common specific minimal metabolic rate, which larger organisms, because of their lower basal metabolism, already attain in less profound hypothermia. The observation that there is, in natural lethargic states, a certain independence between metabolic rate and body temperature, subsequently leads to considerations on the presumable modulating influence exerted by the acid-base balance. Finally, referring to the time limitations of such adaptation strategies, the cold-induced disintegration of metabolic processes with differing temperature dependence is illustrated which, however, will be more pronounced in the intermediate temperature range than in lower cooling. Thus, despite a limited cold tolerance, an extremely profound hypothermia of short duration seems not altogether impossible even for large homeotherms, provided some adequate conditions of rewarming are observed. PMID- 2237882 TI - Performance characteristics of centrifugal pumps with heparin surface coating. AB - Heparin surface coating is one approach to improve the biocompatibility of existing blood pumps used for mechanical circulatory support. Experimental evaluation of centrifugal pumps with heparin surface coating was performed during open chest left heart bypass (3.7 L/min over 6 hours) in two series of bovine experiments. Eight calves (74 +/- 4 kg) were perfused either by heparin surface coated equipment without systemic heparinization or uncoated equipment with systemic heparinization (300 I. U,/kg bodyweight; ACT greater than 400 s). A standard battery of analyses was performed before and at regular intervals after onset of perfusion. At the end of perfusion all pump-heads were gently rinsed. There were no macroscopic clots for both groups whereas macroscopic clots were observed in uncoated tubings introduced for control in the group perfused without systemic heparinization. The hemodynamics were significantly better in the group perfused without systemic heparinization and maintained functional coagulation system. Clinical application of heparin surface coated equipment during resection of thoraco-abdominal aortic aneurysms is showing promising results in 12 patients. PMID- 2237883 TI - Tricuspid valve replacement: factors influencing early and late mortality. AB - Seventy four patients underwent tricuspid valve replacement (TVR), between 1968 and 1983. 93% were female, mean age was 44 +/- 4 years. Tricuspid valve was replaced with a mechanical prosthesis in 52 and a bioprosthesis in 22 patients. Fifty seven patients underwent primary TVR and 17 underwent a secondary TVR following a mean interval of 41 +/- 2 months (SEM) following a previous mitral or tricuspid valve operation. Preoperatively 86% patients were in NYHA class III-IV and congestive cardiac failure (CHF). Early mortality for primary TVR was 36.8% and 35.2% for secondary TVR. Early mortality has been significantly reduced since the introduction of cardioplegic protection for the associated valve lesions. Early mortality was significantly influenced by the reduced preoperative values of FVC and FEV1 in patients with long standing mitral valve disease and by raised preoperative levels of plasma bilirubin and alkaline phosphate in patients with CHF. Risk of thrombotic occlusion and late deaths remained high during the first year after TVR with a mechanical prosthesis. PMID- 2237884 TI - Echocardiographic evaluation of systolic left-ventricular function in infants with critical aortic stenosis before and after aortic valvotomy. AB - Infants with critical aortic stenosis may have global or regional left ventricular contraction abnormalities. In order to evaluate the clinical significance of these contraction abnormalities, we examined the systolic left ventricular function before and after aortic valvotomy in 16 infants operated on between 1980 and 1987. Left ventricular free wall and septal motion were studied by cross sectional echocardiography using the apical 4-chamber view. Enddiastolic and endsystolic left ventricular frames were digitized. The relative systolic reduction of the total left ventricular area (reflecting ejection fraction) as well as of 5 left ventricular sectors (reflecting regional wall motion) was calculated and compared to previously established normal values. Before valvotomy, 8 infants had normal and the other 8 impaired left ventricular systolic wall motion. These latter infants showed hypokinesia of the apex and/or the posterolateral left ventricular wall resulting in a decreased systolic reduction of the total left ventricular area. Four of these infants had evidence of myocardial infarction on intraoperative inspection. Early after operation, the systolic reduction of the total left ventricular area was normal in all infants, and the left ventricular apex and poster-lateral wall were either normo- or hyperkinetic. Follow-up studies of all infants more than 10 months and of 7 infants more than 3 years after operation showed that the left ventricular systolic wall motion remained normal in all, irrespective of whether it was normal or abnormal preoperatively. This study suggests that left ventricular contraction abnormalities in infants with critical aortic stenosis may be reversible and thus do not constitute a contraindication against aortic valvotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237885 TI - An unusual cause of disabling angina following aortic valve replacement. AB - Severe ostial stenosis of the coronary arteries following aortic valve replacement is a potentially lethal complication. The usual presentations are recent onset of severe angina, ventricular arrhythmias, congestive heart failure, and sudden death. It is generally accepted to arise from injury to the coronary arteries during direct cannulation and continuous perfusion of cardioplegia under high pressure during operation. We report on a patient who developed critical left coronary ostial stenosis after aortic valve replacement. The cause for the stenosis was probably related to the over-sizing and orientation of the prosthesis. The prosthesis was replaced and patch angioplasty of the left coronary ostia performed. The patient was well with normal coronary anatomy three years after surgery. PMID- 2237886 TI - The mobilized omentum and muscle flaps in the treatment of infectious complications in cardiovascular surgery. AB - Infection in cardiovascular surgery invariably constitutes a very serious complication that cannot be controlled by antibiotics in all cases. Improved blood supply to the tissue affected by infection largely helps to control these complications. The article reports on three cases in which mobilized muscle and omental flaps helped essentially to heal infectious complications following heart transplantation, aortic valve replacement, and reconstruction of arteries of the lower limb. PMID- 2237887 TI - Carcinosarcoma of the lung, a tumour which has a poor prognosis and is extremely rarely diagnosed preoperatively. AB - Out of about 2,000 patients operated on for lung cancer in the period from 1975 to 1990, four were found with the very rare condition carcinosarcoma. The diagnosis was verified by immunohistochemical investigation. The problems concerning this rare tumour are discussed with reference to four case descriptions and with consideration of the pertinent literature. On the one hand, they comprise the difficulty of making a correct histological diagnosis preoperatively, and on the other hand the poor prognosis, even in the NO stage. PMID- 2237888 TI - Endocrine secreting malignant mediastinal teratoma. AB - Malignant mediastinal teratoma containing yolk sac elements are rare tumours and invariably have a poor prognosis. An elevated alpha fetoprotein level is a useful indicator of the malignant nature and the invasiveness of the tumour. A case with such a tumour who also presented with precocious puberty is described. This patient was treated with radiotherapy and chemotherapy prior to radical surgical excision, and has now survived for over 64 months without evidence of metastases. PMID- 2237890 TI - [Position of heart surgery 1988 in Germany. Report of the Hospital Commission study group of governing Medical officials (AGLMB)]. PMID- 2237889 TI - Thoracic Research scholarship 1989: St. Louis University--new developments in the field of lung transplantation. PMID- 2237891 TI - [Extension of heart surgery capacity in Germany]. PMID- 2237893 TI - Tumors of the heart. Proceedings of the Third Symposium on Cardiac Surgery. Giessen. PMID- 2237892 TI - [Present position of heart surgery in East Germany and prospects]. PMID- 2237894 TI - Clinical aspects of cardiac tumors. AB - Due to surgical advances, cardiac tumors now represent a potentially curable form of heart disease. Primary cardiac tumors are very rare; secondary, metastatic tumors are 10-40 times more frequent. The majority (75%) of primary tumors is benign. Cardiac tumors may produce hemodynamic disturbances, mechanical hemolysis, biochemical effects and constitutional symptoms. According to the anatomic location of the tumor, some special symptoms and physical findings can be grouped with regard to pericardial, myocardial, and endocardial involvement. Several laboratory data (elevated sedimentation rate, anemia, thrombocytopenia etc.) may give additional hints to suggest cardiac involvement in neoplastic disease. Among the diagnostic procedures, two-dimensional echocardiography has become the most important method for non-invasive detection of cardiac tumors. The importance of invasive procedures has declined by the improvement of non invasive imaging techniques, but pressure measurements within the cardiopulmonary system, left-sided, pulmonary angiography as well as coronary angiography give additional useful and necessary information prior to surgery. Within the spectrum of differential diagnosis, particularly mitral, aortic, or tricupid valve disease, bacterial endocarditis, or autoimmune diseases have to be ruled out. Thus, in the vast majority of cases the correct diagnosis can be made. This is crucial for further management of the patient since the majority of primary cardiac tumors can be successfully treated by surgery. PMID- 2237895 TI - Immunology of cardiac tumors. AB - Whereas abundant literature is available on mechanisms imposed by neoplastic diseases on the immune system, only few details are known about immunological parameters of autoreactive mechanisms directed against the heart. This report will focus on cardiac autoreactivity in patients with endomyocardial types of cardiac tumors (e.g. atrial myxomas), Hodgkin's disease, and with neoplastic pericardial effusion. In patients with atrial myxomas antimyolemmal antibodies were significantly increased when compared to non-cardiac controls. Antisarcolemmal antibodies were positive in 100% of trivalent immunoglobulin binding. Antiendothelial antibodies of the IgG type could be found in 86% of patients with atrial myxoma. Circulating immune complexes were present in 6 out of 7 patients. In 107 patients with Hodgkin's disease without pericarditis the presence of antimyolemmal antibodies was lower than in healthy controls. The incidence of antimyolemmal antibodies in 10 patients with pericarditis lymphogranulomatosa was 10%, whereas in postradiation pericarditis 8 of 15 patients demonstrated antimyolemmal antibodies. Antiendothelial antibodies were positive in 7 out of 15 patients. The number of patient lymphocytes available for functional assays is yet too small to permit further conclusions on cellular autoreactive mechanisms in Hodgkin's disease. Antimyocardial antibodies were found both in the serum and in the effusions at least in lower titers in all patients. With regard to in-vitro analysis it can not be excluded that a balance between protective and cytolytic antibodies keeps a normal mean of antibody mediated cytolysis. Analysing the first line of defense, the natural killer cell activity was found significantly increased in neoplastic pericardial effusions, whereas peripheral blood and pericardial effusion showed no lymphocytotoxicity with isolated myocardial cells. PMID- 2237896 TI - Special considerations on primary cardiac tumors in infancy and childhood. AB - Primary cardiac tumors are rare at all ages and are even less common in infants and children. In the vast majority of cases, they are benign tumors that show little tendency to growth. Primary malignant tumors of the heart are exceptionally rare. Rhabdomyomas are the most common type of tumors in infants, followed in frequency by the fibromas and the teratomas. Myxomas are very rare in pediatric patients. Symptoms that derive from the presence of a neoplastic mass are usually due to obstruction or compression. In young symptomatic patients, usually affected by rhabdomyomas, there is little chance of survival without surgery. On the other hand several patients with cardiac neoplasms are totally asymptomatic. The indication for surgery is differenciated according to the severity of the clinical picture. Since 1974, 15 infants with a cardiac tumor have been observed in our hospital. Our recent experience with 5 cases, which are described in this report, confirm our opinion, that the most important fact is the restoration of the best possible heart function. Total resection of a tumor should not always be the main therapeutical aim. Surgical intervention is required for those patients, who develop relevant clinical symptoms. Close observation of the clinical course is mandatory in all patients with a doubtful indication for operation. PMID- 2237897 TI - MR and CT for detection of cardiac tumors. AB - Although echocardiography is mostly applied for the diagnosis of heart tumors there are restrictions concerning the representation of the mediastinal and cardial topography in spite of the usage of transoesophageal echocardiography. Computed tomography (CT) and magnetic resonance imaging (MR) are able to give a full representation of the heart and also the thorax with mediastinum, pleura, and lungs. Not only for the diagnosis of various kinds of heart tumors but also for decisions concerning the therapy, the detection of postoperative complications and development are CT and MR very valuable procedures. The ability to deliver a complete cross-section of all cardial, mediastinal, pulmonal and thoracic structures--in contrast to angiocardiography--and without any anatomic restrictions in contrast to echocardiography--is another advantage of CT and MR. Because of the fullness of information CT and MR supply these procedures are especially used for the detailed planning of operative procedures. They are also a big help in determining whether surgery might have to be excluded because a complete tumor resection is not possible anymore. PMID- 2237898 TI - Classification of malignant cardiac tumors with respect to oncological treatment. AB - Because of the small incidence of primary cardiac neoplasms there have been no randomized clinical trials to establish rational therapeutic strategies. Surgery is the first choice of therapy in all patients with small cardiac neoplasms. But it is not known whether adjuvant chemotherapy may be benefitial in patients in whom "curative" surgery has been performed. Chemotherapy must be considered as the first choice of therapy in primary cardiac tumors with extracardiac metastases. Combination of several agents is more effective than single-agent therapy. Radiation should be applied in less sensitive tumors only if surgery is not feasible and prior chemotherapy has failed. In patients in whom cardiac surgery was performed with a curative aim, chemotherapy but not radiation is the adjuvant therapy of choice. Patients with metastatic tumors to the heart should be treated according to the established rules for the involved tumor. Therapeutic strategy depends on the kind of tumor and the cardiac structure involved. Tumor spread to the pericardium will cause pericarditis or pericardial effusion up to pericardial tamponade. Instillation of tetracyclines, isotopes and chemotherapeutic agents in the pericardial space have been successfully applied to prevent recurrent effusion. Radiation did prolong life in patients with pericardial metastases as compared with repeated pericardiocentesis. Additional cardiac damage may be induced by radiation as well as by drugs. A trial with chemotherapy can be useful in all sensitive cardiac tumors. PMID- 2237899 TI - Surgical treatment of cardiac neoplasms: 32-year experience. AB - In the last 25 years, there have been extraordinary advances and new developments in diagnosis and surgical treatment for cardiac tumors. New diagnostic methods have almost replaced the need for cardiac catheterization and ventriculography. During cardiopulmonary bypass the myocardium can be protected by means of hypothermia and cardioplegia. Various techniques have been developed to excise cardiac tumors. Depending upon the site and the extent of the neoplasm, additional cardiac repair may be required, including bypass grafting or valve replacement. Primary tumors of the heart are usually intracavitary lesions and more than 75% are benign. Myxomas are the most common cardiac tumors. They are usually attached to the intraatrial septum in the left atrium close to the fossa ovalis. Left atrial myxomas must be distinguished from mitral valve disease, since the clinical presentation may suggest rheumatic feaver and acute myocarditis. Since 1957 we have operated upon 71 patients with myxomas with no deaths. Removal of a myxoma should be undertaken more aggressively and thoroughly than formerly was recommended. Rhabdomyomas are usually multiple tumors, and most often they involve the ventricular myocardium. Because these tumors do not grow rapidly, surgical resection can be successful. It the tumor is large, it can be partially resected to release the obstruction. We have operated upon 3 patients with this tumor. Cardiac fibromas are the second most common tumor in infants and children. These are usually solitary tumors which compress the surrounding structures as they grow. Complete excision of fibromas is difficult since the tumors tend to grow large. We have operated upon 11 patients with this tumor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237900 TI - Primary cardiac tumors: experience at the University of Minnesota. AB - A review of all primary cardiac tumors seen at the University of Minnesota or entered in the Registry of Cardiovascular Disease, affiliated with the University of Minnesota, between 1959 and 1989. Of a total of 124 primary cardiac tumors, 103 (83%) were benign and 21 (17%) were malignant. Atrial myxomas (51 cases) accounted for 42% of all tumors and 50% of benign neoplasias. The remaining 51 benign tumors were, in order of frequency: rhabdomyomas, 14 (13%), papillomas, 12 (11%), fibromas, 9 (9%), hamartomas, (4%), teratomas (2%), lipomas (2%), mesotheliomas (2%), fibroelastomas, hemangiomas, glomangiomas, and a few others. The 21 malignant tumors, all sarcomas, were, in order of frequency: rhabdomyosarcomas, 6 (29%), angiosarcomas, 4 (19%), myxosarcomas, 3 (14%), fibrosarcomas, 2 (10%), and one each leiomyosarcoma, reticulum cell sarcoma, and liposarcoma. There were 3 cases of spindle cell sarcoma (14%) originating in the great vessels: 1 in the pulmonary artery and 2 in the aorta. The prognosis of the resected benign tumors was good, with no complications of recurrences for up to 15 years of follow-up. Tumors that could not be excised included mostly rhabdomyomas, in newborns, and cavernous hemangiomas involving most of the heart, with poor prognosis. Malignant tumors of the heart had a very poor prognosis, even when operated on promptly after diagnosis. The mean survival time of these patients was 5 months after resection, even when followed with chemotherapy and/or radiation; 26% of the tumors had already metastasized at the time of operation. Extensive resections in malignant tumors did not render satisfactory results. PMID- 2237901 TI - Primary cardiac tumors--French studies of 533 cases. AB - The present study combining the Eisenman French Joint Study and the Broussais Hospital experience is based upon 533 primary cardiac tumors which were operated on in France and by French-speaking teams during a period of about 25 years. The diagnosis of heart tumors was facilitated by the progressive development of new examination techniques. Echocardiography seems to be the simplest, safest, and the most reliable diagnostic method and is used more frequently then angiocardiography. Cardiac tumors occur at every age with a prevalence for females. About 10% of the surgically treated primary cardiac tumors were malignant (53 patients) with a constantly poor prognosis. The mean survival time of this collective after operation was only 1.5 years. 8% of the benign cardiac tumors were non-myxomatous (36), including fibromas, rhabdomyomas, and hamartomas. The mean age of this group was lower (21 years) than in the collectives with myxomas or with malignant cardiac tumors. Another characteristic of non-myxomatous tumors is the involvement of the ventricles by the neoplasm (88%). Complete resection of the tumor was possible in 75%, only 3 operative deaths occurred. Myxomas are the most common tumors of the heart, representing 83% of all primary cardiac tumors (444). Female patients were involved more often than males. The age of the patients ranged widely from 2.5 to 82 years. The typical localization of the myxomas was the left atrium (83%), followed by the right atrium (11%). In 5 cases myxomas were found multilocalized. Very often myxomas were mimicing valvular disease. In more than 30% peripheral embolization provoked the diagnosis. Only in 2% was the tumor totally asymptomatic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237902 TI - Incidences and surgical aspects of cardiac myxomas in Bulgaria. AB - 63 patients with cardiac tumors underwent operative treatment between January 1970 and December 1988. Three additional patients refused the operation, despite the large left atrial myxomas and obstruction of the mitral valve, recognized by echocardiography. 62 patients had benign tumors: the only malignant neoplasm was a fibrosarcoma, originating from the right ventricle. Myxomas were found in 57 patients: 54 were located in the left and 2 in the right atrium. In one case the myxoma originated from the left ventricle. The hospital mortality of the 22 patients who underwent excision of cardiac myxomas between 1970 and 1984 was 18.18% (4 deaths), and 2.44% (1 death) of 41 patients operated on from 1984 to 1988 for cardiac tumors (35 of them with myxomas). During the follow-up time of 6 to 140 months, recurrence of myxomas occurred in only one patient, 4 years after surgery for multifocal myxoma in the left atrium. Surgical excision of the myxoma is the only acceptable therapy able to cure. Without surgical treatment, the medium and long-term prognosis is fatal. Therefore once the cardiac myxoma is identified by two-dimensional echocardiography, the tumor should be removed even in patients without symptoms. The removal of myxomas doesn't require excision of the full thickness of the interatrial septum or ventricular wall. The risk of postoperative arrhythmias after extensive excision increases. Conduction disturbances may be related to the resection of a large area of the atrial septum or wall. No recurrences have been registered after less radical procedures-- removal with excision only of the underlying endocard. PMID- 2237903 TI - Tumors of the heart. Incidence and clinical importance of cardiac tumors in Japan and operative technique for large left atrial tumors. AB - In 1986, a total of 18 430 open-heart procedures was performed in Japan. Whereas surgery of congenital heart disease amounted to 46% of all operations, cardiac tumors caused only 0.8% (148 cases). The results of an investigation based on data from 9 Japanese institutes over a period of 5 years show that myxomas are the most frequent tumors of the heart (74 out of 89 cases). Among 89 cardiac tumors there were 6 malignant neoplasms. More females were affected than male patients. Most of the myxomas were localized in the left atrium (66 out of 74). The majority of the myxomas originated from the atrial septum, two myxomas derived from atrio-ventricular valves. Inflow and outflow obstruction, valvular dysfunction and arrhythmias were the most common symptoms of cardiac tumors. In 88 patients resection of the tumor could be performed, in 4 cases combined with mitral valve replacement and in one case mitral valvuloplasty. In one patient, only a tumor biopsy was possible. Reoperation for recurrent myxoma had to be carried out in 4 patients after an interval of 1-6 years. In the case of a large left atrial tumor the circular incision of the biatrium is preferred by our group. This large approach facilitates the removal of the tumor, enables the repair of the left atrial posterior wall and atrial septum as well as the surgery of the mitral valve. If necessary, this surgical technique can easily be switched to cardiac autotransplantation. With regard to new operative procedures we are convinced that surgical intervention for cardiac tumors can be applied more widely in future. PMID- 2237904 TI - Incidence and clinical importance of cardiac tumors in China--review of the literature. AB - The first successful excision of a left atrial myxoma in China was performed in 1962. Till October 1988, 656 surgical cases of cardiac tumors have been reported in the Chinese literature. The diagnosis of all excised tumors was confirmed by pathologic studies. The age of patients ranged from 46 days to 72 years. Among these 656 cases, 647 tumors were benign (97%) and 9 tumors were malignant (3%). 633 myxomas (97.8%) represented the vast majority of the benign cardiac tumors. In 26 cases, myxomas were found multilocalized. Before 1975, echocardiography could not be performed universally in our country, and diagnosis often failed. At present, echocardiography is the most used and the most reliable examination method for cardiac tumors in China. The majority of the patients presented clinical symptoms of congestive heart failure with palpitation, dyspnoe, syncope, and hemoptysis. In 99% the main abnormality was an atypical and frequently variable heart murmur. Arterial embolization occurred in 15%. In all patients the myxomas was removed as a whole with its attachment to the interatrial septum or the atrial wall to prevent recurrence. Examination of all heart chambers should be performed to exclude multilocalized tumors. The operative mortality ranged between 5.8 to 13%. The recurrence rate of myxomas in China was reported to amount to 3%. PMID- 2237905 TI - Tumors of the heart. Experiences at the Giessen University Clinic. AB - Of 54 cardiac tumors operated upon in our clinic, 42 were classified as benign and only 12 as malignant. The major part of the benign tumors were myxoma, mainly located in the left atrium. While smaller tumors could be treated by local resections, extensive resections were necessary in 14 patients with greater tumors followed by reconstructions of the pulmonary and caval vein, mitral and tricuspid valve, and major parts of the right and left ventricular wall. In one patient with a huge benign myxoma, tumor exposition and total resection could only be achieved by an autotransplantation of the heart. While mortality after surgical therapy of benign tumors was only 1.4% (1/42) within a mean follow-up time of 48 months, the prognosis of malignant tumors is still fatal with a mortality of 50% (6/12) within a mean follow-up time of 24 months, despite additional chemotherapy or radiation. PMID- 2237906 TI - The effect of submandibular gland removal on testicular and epididymal parameters. AB - The effect of sialoadenectomy (submandibular gland removal) for four weeks duration was studied in five C3H mice and four sham-operated controls. This preliminary experiment using small numbers of animals indicated that sperm production parameters were lowered in sialoadenectomized animals although there were no significant differences between the sialodenectomized and sham-operated group. In a second experiment using larger numbers of animals, significant differences in testicular weights, epididymal weights, and testis weights were noted. These parameters were reduced only 10-14% from control levels. Epididymal sperm head counts were reduced 10% after sialoadenectomy but the two groups were not significantly different (P less than 0.05). No difference in testicular histology was observed. The present report contrasts to that of Tsutsumi et al. (1986) who indicate that submandibular removal with subsequent depletion of epidermal growth factor (EGF), is extremely deleterious (40-55% decreases in spermatid and sperm content) to the progress spermatogenesis. PMID- 2237907 TI - Ultrastructural study of oogenesis in the acoel turbellarian Convoluta. AB - An ultrastructural investigation of oogenesis has been carried out on the acoel turbellarian Convoluta psammophyla. Developing female germ cells are not contained in well delimited ovaries but are freely distributed in the parenchyma and are surrounded by narrow cytoplasmic projections of accessory-follicle cells. Oogenesis can be divided into two periods, the previtellogenic and the vitellogenic phase. In the first period the oocyte undergoes a number of cell differentiations necessary for the intense biosynthetic activity of the second period. The ample development of nucleolus, ribosomes, endoplasmic reticulum and Golgi complexes along with the appearance of large lipid droplets and clusters of electron dense granules characterize the previtellogenic phase. The formation of yolk globules is the main feature of the second period of oogenesis. It occurs by an autosynthetic mechanism involving endoplasmic reticulum and Golgi complexes, since no endocytotic activity has been detected in the developing oocyte. The electron dense granules apparently move towards the cortical ooplasm during the late vitellogenic phase and take part in egg covering formation. Hypotheses on the role of follicle cells and on the phylogenetic significance of a comparative analysis of egg inclusions with homologous structures of other Turbellaria are suggested. PMID- 2237908 TI - Immunohistochemical localisation of the thymidine analogue 5-bromo-2-deoxyuridine in insect tissue: preservation of cellular ultrastructure. AB - The incorporation of the thymidine analogue 5-bromo-2-deoxyuridine and its detection by a specific monoclonal antibody, is proving a valuable tool in the study of cell kinetics and proliferation. To date, however, its use has been largely restricted to the light microscope level. The fixatives and processing required do not preserve the cellular ultrastructure. This paper details an immunohistochemical procedure which retains both structural details and preserves sufficient antigenicity for the use of the monoclonal at the electron microscopical level. PMID- 2237909 TI - Embryonic and adult neurones of the housefly (Musca domestica) in culture. AB - This paper provides a detailed description of the dissociation and maintenance in culture of cells derived from embryonic tissue and from the central nervous system of adult housefly, Musca domestica. Dissociation of embryonic tissue produced several cell types of which muscle and neurone-like cells predominated. These cells were morphologically distinct once development had started in vitro with muscle cells often producing rhythmic contractions. Neurones had small cell bodies (less than 10 mum) and showed extensive outgrowth of neurites. Neuronal cell bodies readily sealed onto patch pipettes and with pipette solutions containing nicotinic agonists, single channel currents could be recorded. With cell-attached patches, these currents were inward at the cell resting potential and reversed with depolarization. Channels with two different conductances could be seen in the majority of patches. PMID- 2237910 TI - Cleaning insect oocytes by dissection and enzyme treatment. AB - Vitellogenic oocytes from the cockroach Blattella germanica were dissected free of the surrounding follicle cell layer. The continued presence of a resting potential indicated that the defolliculated oocytes remained viable. In other experiments, lysozyme was injected into last nymphal instars; scanning electron micrographs showed that the bacteroids normally found between the follicle cell epithelium and the oocyte membrane were removed by this treatment. Oocytes from injected animals were known to be viable because they developed into living progeny. To assess the mode of action of lysozyme, defolliculated oocytes were exposed in vitro to lysozyme and then a hypotonic rinse; scanning electron micrographs showed that these oocytes were largely free of bacteroids. PMID- 2237911 TI - Comparison of the disposition and in vitro metabolism of 4-vinylcyclohexene in the female mouse and rat. AB - 4-Vinylcyclohexene (VCH) is a chemical to which humans are exposed in the rubber industry. A chronic carcinogenicity bioassay conducted by the National Toxicology Program showed that oral administration of VCH induced tumors in the ovaries of mice but not in those of rats. The hypothesis tested was that the species and organ specificity of VCH toxicity was due to differences in the disposition of VCH between the female rat and mouse. Therefore, the disposition of a single oral dose of 400 mg/kg [14C]VCH was studied in female B6C3F1 mice and Fischer 344 rats. Mice eliminated greater than 95% of the dose in 24 hr, whereas rats required 48 hr to eliminate greater than 95% of the dose. The major routes of excretion of [14C]VCH-derived radioactivity were in the urine (50-60%) and expired air (30-40%). No evidence was obtained to indicate that the ovaries of either species retained VCH as a parent compound or as radioactive equivalents. A dramatic difference was observed between the rat and mouse in the appearance of a monoepoxide of VCH in blood from 0.5 to 6 hr after VCH administration (800 mg/kg, ip). VCH-1,2-epoxide was present in the blood of mice with the highest concentration at 2 hr (41 nmol/ml). The blood concentration of VCH-1,2-epoxide in rats was less than 2.5 nmol/ml at all times examined. VCH-7,8-epoxide was not present in the blood of either species at the level of detection. These findings were supported by in vitro studies of VCH epoxidation by liver microsomes. The rate of epoxidation of VCH (1 mM) to VCH-1,2-epoxide was 6.5-fold greater in mouse liver microsomes than that in rat liver microsomes. The species difference in the rate of epoxide formation by the liver may be an important factor in the species difference in susceptibility to VCH-induced ovarian tumors. PMID- 2237912 TI - The role of epoxidation in 4-vinylcyclohexene-induced ovarian toxicity. AB - 4-Vinylcyclohexene (VCH) is present in gases discharged during synthetic rubber production. Chronic treatment of B6C3F1 mice and F-344 rats with VCH by gavage has been shown to induce ovarian tumors in mice but not in rats. Our objective was to understand the mechanism of the species difference in VCH-induced ovarian tumors. Since a critical step in the induction of ovarian tumors is destruction of the small oocyte, small oocyte counts obtained from serially sectioned ovaries were used as an index of toxicity. VCH or its epoxide metabolites [VCH-diepoxide, VCH-1,2-epoxide, and VCH-7,8-epoxide (in mice only)] were given to 28-day-old female mice and rats in corn oil, ip, at doses ranging from 0.07 to 7.4 mmol/kg body wt/day for 30 days. The dose which reduced the small oocyte count to 50% that of control was defined as the ED50. In mice, the ED50 for the reduction in small oocytes by VCH was 2.7 mmol/kg, whereas, no detectable oocyte loss occurred in rats at the highest dose of VCH (7.4 mmol/kg). The potency of the epoxides of VCH was greater than that of VCH in both species. The ED50 for oocyte loss by VCH 1,2-epoxide in mice and rats was 0.5 and 1.4 mmol/kg, respectively. In mice, VCH 7,8-epoxide had comparable potency to VCH-1,2-epoxide (ED50 = 0.7). VCH diepoxide was even more potent with ED50 values of 0.2 and 0.4 mmol/kg, in mice and rats, respectively. The dose response of the blood concentration of VCH-1,2-epoxide in mice after VCH showed that doses of VCH which caused minimal toxicity had the lowest blood level of this ovotoxic epoxide. Pretreatment of mice with the cytochrome P450 inhibitor chloramphenicol (200 mg/kg, ip) inhibited VCH epoxidation in vivo and in vitro and partially protected mice from VCH toxicity. Thus it appears that metabolism of VCH to epoxides and their subsequent destruction of oocytes are critical steps in VCH-induced ovarian tumors. Rats may be resistant to ovarian tumor induction by VCH because the amount of VCH converted to epoxides is insufficient to produce oocyte destruction. PMID- 2237913 TI - Increased hepatic nicotine elimination after phenobarbital induction in the conscious rat. AB - Elimination parameters of [14C]nicotine in conscious rats receiving nicotine (0.3 mg/kg) either intravenously or orally were studied. The oral availability of unchanged nicotine, derived by comparison of the respective areas under the concentration vs time curves (AUC), was 89%, indicating low hepatic extraction ratios of about 10%. Pretreatment of rats with phenobarbital (PB) markedly increased hepatic first-pass extraction of nicotine. The oral availability of unchanged nicotine in plasma dropped to 1.4% of the corresponding values obtained from PB-treated rats receiving nicotine iv. After PB pretreatment, the clearance of iv nicotine was increased approximately twofold over controls, much less than the observed more than ninefold increase of hepatic first-pass extraction. It is assumed that extrahepatic metabolism contributed significantly to the rapid removal of nicotine from the plasma. The elimination of cotinine, originating from nicotine administered either po or iv, was significantly increased by PB pretreatment, as determined by the ratio of corresponding AUCs. The pattern of nicotine metabolites in urine also indicated an increase in the rate of cotinine metabolic turnover. The amount of norcotinine in the organic extract of urine paralleled PB microsomal enzyme induction. The ratio between urinary concentrations of the normetabolite and cotinine correlated strongly with the PB induced state of rat liver. This may be a suitable indicator of PB-inducible hepatic cytochrome P450 isoenzyme(s). Since smoking habits in man are feedback regulated by nicotine plasma concentrations, a similar increase of nicotine elimination by microsomal enzyme induction in man may be of relevance for tobacco consumption. PMID- 2237914 TI - Evidence for the participation of activated oxygen species and the resulting peroxidation of lipids in the killing of cultured hepatocytes by aryl halides. AB - Primary cultures of rat hepatocytes were used to explore the mechanisms of the toxicity of aryl halides. The sensitivity of the hepatocytes to chloro-, bromo-, and iodobenzene was enhanced by inhibition of glutathione reductase with 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU). In each case, the increased cell killing depended on the metabolism of the toxicant, a result shown by the protective effect of SKF-525A, an inhibitor of mixed function oxidation. BCNU decreased the metabolism of [14C]bromobenzene and the covalent binding of its metabolites by 20%. Chelation by deferoxamine of a cellular source of ferric iron prevented the cell killing in the presence or absence of BCNU. Deferoxamine had no effect on the metabolism or the covalent binding of [14C]bromobenzene. Similarly, the antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD) reduced the cell killing and had no effect on the metabolism of [14C]bromobenzene. Thus, the toxicity of the three aryl halides was manipulated in ways that modify the sensitivity of hepatocytes to an oxidative stress, and the changes in cell killing occurred without parallel changes in the metabolism of [14C]bromobenzene or the covalent binding of its metabolites. PMID- 2237915 TI - Toxicokinetic study of norfloxacin-induced arthropathy in juvenile animals. AB - A toxicokinetic study of norfloxacin-induced arthropathy in juvenile animals was undertaken using nalidixic acid as a standard drug. Norfloxacin and nalidixic acid were subcutaneously administered to rats and rabbits, orally administered to dogs, and norfloxacin was orally dosed to monkeys once a day for 7 consecutive days. Of the dose levels tested, the minimum arthropathic doses of norfloxacin were 100, 25, and 50 mg/kg/day in rats, rabbits, and dogs, respectively. At these doses, the peak serum concentrations (Cmax) on Day 6 were 16.1, 9.73, and 5.11 micrograms/ml, and the areas under the serum concentration/time curve (AUC0--- infinity) were 31.9, 22.9, and 26.2 micrograms.hr/ml, in respective animals. Monkeys showed no arthropathy with norfloxacin at doses of less than 500 mg/kg/day, at which the Cmax and AUC0----infinity were 15.6 micrograms/ml and 103 micrograms.hr/ml, respectively. The minimum arthropathic doses of nalidixic acid were 50, 100, and 25 mg/kg/day in rats, rabbits, and dogs, respectively. The Cmax and AUC0----infinity of nalidixic acid were higher than those of norfloxacin in all animals. Joint tissues took up more norfloxacin than nalidixic acid, but when arthropathy was present the articular cartilage concentrations of the two drugs were in the same range. The penetration of norfloxacin into the articular cartilage was the same regardless of the joint's anatomical locations, but differed among species, being highest in rats and lowest in monkeys. The Cmax and AUC0----infinity of norfloxacin in animals at their arthropathic doses were far higher than those measured clinically in children, whereas those of nalidixic acid in animals did not differ much from its clinical parameters. PMID- 2237916 TI - Efflux of endogenous zinc liberated from metallothionein and alcohol dehydrogenase in the liver by replacement with cadmium. AB - Efflux of endogenous zinc (Zn) from the liver was examined to aid elucidation of the mechanisms of the discriminative uptake between the essential heavy metal Zn and the nonessential heavy metal cadmium (Cd). Cd was injected intravenously into rats with or without pretreatment of a small dose of Cd 6 or 24 hr earlier. The concentration of Zn in the whole liver decreased with time after Cd injection and the extent of the decrease was more apparent in the liver that contained the Zn bound to metallothionein (MT) by pretreatment. Time course curves of Cd and Zn in liver supernatants were identical to those of the corresponding whole livers, indicating that the changes observed in the whole livers were due to the changes in the supernatants. Distribution profiles of Cd and Zn by gel filtration chromatography indicated that Cd replaced Zn bound to both alcohol dehydrogenase (ADH) and MT. The decrease of Zn in the liver caused by Cd injection was explained by the efflux of the Zn liberated from ADH and MT, which suggests that efflux of Zn ions but not Cd ions occurs from the liver. The results are discussed from the viewpoint of discriminative uptake between Cd and Zn by the liver. PMID- 2237917 TI - Synaptic terminal degeneration and remodeling at the rat neuromuscular junction resulting from a single exposure to acrylamide. AB - Repetitive exposure to low doses of acrylamide results in extensive pathological changes at the neuromuscular junction (NMJ), but it remains undetermined if a single exposure to a larger dose will produce a similar neuropathological outcome. In the present study, morphometric and ultrastructural analyses of rat soleus NMJ were performed to determine early pathological effects of an intraperitoneal injection of 100 mg/kg acrylamide. Widespread nerve terminal degeneration, terminal sprouting, and endplate lengthening were evident as early as 4 days after injection. Degenerating terminal branches were swollen and exhibited enhanced argyrophilia. Ultrastructurally, the majority of terminals exhibited axolemmal abnormalities, neurofilament accumulations, and a paucity of synaptic vesicles; occasional swollen terminals lacked neurofilaments but contained increased numbers of tubulovesicular profiles. This early morphological pattern of nerve terminal changes suggests that acrylamide may disrupt both synaptic vesicle recycling and neurofilament degradation. These findings indicate that a single high dose of acrylamide triggers pathological lesions and remodeling in motor nerve terminals virtually identical to those resulting from multiple low doses. PMID- 2237918 TI - Estimating the risk of liver cancer associated with human exposures to chloroform using physiologically based pharmacokinetic modeling. AB - A physiologically based pharmacokinetic (PB-PK) model for CHCl3 has been used to prepare estimates of the probability that human populations exposed to low levels of CHCl3 will develop liver tumors similar to those seen in rodent bioassays. The PB-PK model for CHCl3 was based on a model reported earlier by Corley et al. (1990), but this model differed from that of Corley et al. in that it was also capable of describing a pharmacodynamic endpoint: induction of cytotoxicity in the liver of CHCl3-exposed animals produced by reactive metabolites of CHCl3. Pharmacodynamic descriptions in this model were derived from experimental measurements of cell replication ([3H]thymidine incorporation) as well as from quantitative histopathology in the liver of rats and mice. Two different approaches were used for hazard evaluation: (1) a "Safety Factor" approach based on no observed effect levels for liver tumors. and (2) calculation of lower confidence limits on risk-specific doses with the GLOBAL83 computer program. In each case, cytotoxicity produced by reactive CHCl3 metabolites was used as the measure of "dose" to the liver. The Safety Factor approach suggested that continuous exposure of human populations to concentrations of CHCl3 less than 2840 ppb in air or 13,900 ppb in water would not be likely to significantly increase the risk of developing liver tumors. The second approach suggested a "plausible upper 95% confidence limit" of 1 x 10(-5) for lifetime excess cancer risk for human populations continuously exposed to 2200 or 13,100 ppb CHCl3 in air or water, respectively. PMID- 2237919 TI - Acetaminophen hepatotoxicity: correspondence of selective protein arylation in human and mouse liver in vitro, in culture, and in vivo. AB - Human and mouse liver were exposed to an APAP-activating system, in vitro. Subsequent immunochemical analysis of electrophoretically separated proteins with an affinity-purified anti-APAP antibody indicated that when a cytosolic fraction from human liver was incubated with APAP, an NADPH-regenerating system, and mouse microsomes selective APAP binding occurred predominantly to proteins of approximately 38, 58, and 130 kDa. To evaluate whether similar proteins are targeted in situ, primary cultures of human hepatocytes were treated with 10 mM APAP for 4 hr prior to immunochemical analysis. APAP binding was again detected in protein bands of approximately 38, 58, and 130 kDa. In addition, selective binding was also noted to other cytosolic protein bands, e.g., approximately 52 and 62 kDa. For mouse liver, the majority of the binding, in vitro or in culture, was to proteins of approximately 44 and 58 kDa with lesser binding to proteins of approximately 33 and 130 kDa among others. By contrast, at the times monitored, little covalent binding was detected in the 44-kDa region in the human liver experiments. Most noteworthy was the finding that when the protein arylation patterns on liver samples from a human APAP fatality were compared to those from a mouse given a hepatotoxic dose of APAP, the binding patterns were similar to those detected after the in vitro and the culture experiments with mouse and human livers. Furthermore, an immunohistochemical analysis revealed that as with the mouse, APAP covalent binding in the human liver exhibited a distinct zonal pattern consistent with centrilobular binding. That APAP arylation of the 58- and 130-kDa proteins was observed in livers from both mice and humans suggests that the mouse provides a valid model for studying the mechanistic importance of covalent binding. Elucidation of the identities and functions of the common targeted proteins may clarify their toxicological significance. PMID- 2237920 TI - In vivo effects of T-2 mycotoxin on synthesis of proteins and DNA in rat tissues. AB - Rats were given an ip injection of T-2 mycotoxin (T-2), the T-2 metabolite, T-2 tetraol (tetraol), or cycloheximide. Serum, liver, heart, kidney, spleen, muscle, and intestine were collected at 3, 6, and 9 hr postinjection after a 2-hr pulse at each time with [14C]leucine and [3H]thymidine. Protein and DNA synthesis levels in rats were determined by dual-label counting of the acid-precipitable fraction of tissue homogenates. Rats given a lethal dose of T-2, tetraol, or cycloheximide died between 14 and 20 hr. Maximum inhibition of protein synthesis at the earliest time period was observed in additional rats given the same lethal dose of the three treatments and continued for the duration of the study (9 hr). With sublethal doses of T-2 or tetraol, the same early decrease in protein synthesis was observed but, in most of the tissues, recovery was seen with time. In the T-2-treated rats. DNA synthesis in the six tissues studied was also suppressed, although to a lesser degree. With sublethal doses, complete recovery of DNA synthesis took place in four of the six tissues by 9 hr after toxin exposure. The appearance of newly translated serum proteins did not occur in the animals treated with T-2 mycotoxin or cycloheximide, as evidenced by total and PCA-soluble serum levels of labeled leucine. An increase in tissue-pool levels of free leucine and thymidine in response to T-2 mycotoxin was also noted. T-2 mycotoxin, its metabolite, T-2 tetraol, and cycloheximide cause a rapid inhibition of protein and DNA synthesis in all tissue types studied. These results are compared with the responses seen in in vitro studies. PMID- 2237921 TI - The B lymphocyte is the immune cell target for 2',3'-dideoxyadenosine. AB - 2',3'-Dideoxyadenosine (ddA) is a nucleoside analogue with anti-HIV activity and one of its metabolic products, 2',3'-dideoxyinosine (ddI), has shown promising results in clinical trials for the treatment of acquired immunodeficiency syndrome (AIDS). Because AIDS viruses target the immune system, it is important to understand the potential effects of anti-AIDS drugs, including natural nucleosides, on the immune system. Previous immunotoxicological studies have shown that 22 treatments with ddA to female B6C3F1 mice over a period of 30 days had no effect on cell-mediated immunity, including the mixed lymphocyte reaction and response to mitogenic signals, but suppressed in vitro IgM plaque-forming cell (PFC) response to sheep red blood cells. The present studies show that suppression of the IgM PFC response was dose dependent with a 96% reduction in IgM PFCs/10(6) spleen cells at the highest dose (350 mg/kg). The in vivo IgM PFC response to DNP-Ficoll and the in vitro IgM PFC response to lipopolysaccharide, both T-independent antigens, were also suppressed in the spleens of ddA-treated mice. The analysis of splenocyte subtypes shows no change in the percentage of B cells (surface immunoglobulin positive cells), T helper cells (L3T4 positive cells), and T suppressor cells or T cytotoxic cells (Lyt-2 positive cells) in the spleens of ddA-treated mice. In vitro separation and reconstitution studies in which the IgM PFC response was monitored indicated that the B lymphocyte rather than the T lymphocyte or antigen-presenting cell is the primary cell targeted by ddA. This information provides a data base for further mechanistic study and may reflect on the clinical use of other nucleoside analogues, e.g., ddI by providing the clinician with information indicating the potential decrease in humoral immunity. PMID- 2237923 TI - Mechanism of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) PMID- 2237922 TI - Propanil-induced methemoglobinemia and hemoglobin binding in the rat. AB - Administration of [ring-U-14C]propanil (3,4-dichloropropionanilide) to male Sprague-Dawley rats (30, 100, and 300 mg/kg, ip) increased the formation of methemoglobin at the two highest doses. Following a propanil dose of 100 mg/kg, methemoglobin formation attained a maximum level of 5% by 1.5 hr and declined to normal levels (approximately 2.5%) by 12 hr. Hemoglobin binding attained a maximum level of 50 pmol/mg protein by 12 hr, and remained constant for 24 hr. Following a propanil dose of 300 mg/kg, methemoglobin formation attained a maximum level of 24% by 4.5 hr, and declined to a level of 5% by 24 hr. Hemoglobin binding attained a maximum level of 425 pmol/mg protein by 12 hr, and remained constant for 24 hr. Hemoglobin binding was also detected at the lowest propanil dose (10 pmol/mg protein) even though methemoglobin formation was not observed. HPLC analysis of alkaline-treated hemoglobin from propanil-treated rats indicated the presence of one radiolabeled compound with the same HPLC retention time as 3,4-dichloraniline. These data are consistent with the concept that propanil is converted to N-hydroxy-3,4-dichloroaniline in the liver. Subsequently, this metabolite enters the erythrocyte and is oxidized by hemoglobin to 3,4-dichloronitrosobenzene with concomitant conversion of oxyhemoglobin to methemoglobin. The 3,4-dichloronitrosobenzene binds to cysteine residues on hemoglobin as the corresponding sulfinic acid amide adduct. These data suggest that human exposure to propanil may be monitored in the absence of observable toxicity by the analysis of propanil metabolites bound to hemoglobin. PMID- 2237924 TI - Developmental toxicology of industrial alcohols: a summary of 13 alcohols administered by inhalation to rats. AB - The developmental toxicology of 13 industrial alcohols (methanol, ethanol, 1 propanol, isopropanol, 1-butanol, 2-butanol, tertiary-butanol, 1-pentanol, 1 hexanol, 2-ethyl-1-hexanol, 1-octanol, 1-nonanol, and 1-decanol), and the behavioral teratogenicity of 4 of these alcohols, were assessed in a series of experiments. The results of individual alcohols have been published previously, but the present paper summarizes the results in view of structure-activity relationships among these alcohols. The alcohols were administered by inhalation for 7 hours per day (6 hours/day for 1-decanol) on gestation days 1-19 to groups of approximately 15 pregnant Sprague-Dawley rats. For developmental toxicology evaluations, dams were sacrificed on gestation day 20. Fetuses were serially removed, weighed, sexed, and examined for external malformations. The frequency of visceral malformations and variations was determined in one-half of the fetuses, and the frequency of skeletal deviations was determined in the other half. Behavioral teratology endpoints were investigated in groups of 15 pregnant rats exposed to one of four alcohols (ethanol, 1-propanol, 1-butanol, and tertiary-butanol) and also involved groups of 18 male rats which were exposed to the same concentrations of each alcohol for 6 weeks, and then mated to untreated females. In the behavioral teratology evaluations, all litters were culled to eight pups and fostered to unexposed mothers. Offspring were tested from days 10 90 on a series of behavioral tests designed to evaluate neuromotor integrity, activity levels, learning, and memory. Additionally, brains were removed from 10 offspring per group at 21 days of age, and were dissected into cerebrum, cerebellum, brainstem, and midbrain; these samples were assayed for steady-state levels of protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, 5-hydroxytryptamine (serotonin), substance P, B-endorphin, and met-enkephalin. Congenital malformations were noted for methanol, 1-propanol, isopropanol, and 1-butanol, but only at concentrations in excess of 5000 ppm. These concentrations also produced toxicity in the maternal animals; thus, there was little evidence of selective developmental toxicity among the alcohols. Although sporadic behavioral and neurochemical deviations were detected, no consistent pattern of effects was seen for any of the alcohols we tested. It should be noted that alcohols with chain lengths longer than the butyl series could not be generated as vapors at sufficiently high concentrations to produce observable toxicity in the maternal animals. This limits the generality of these findings to the possible developmental effects of these alcohols when taken through other routes of exposure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2237925 TI - Growth and development in the rat during sub-chronic exposure to low levels of hydrogen sulfide. AB - The effects of low levels of hydrogen sulfide (H2S) on mammalian growth and development are unknown although it has long been postulated that H2S can inhibit critical developmental functions through the cleavage of disulfide bonds and chelation of essential metal ions. Gravid rat dams exposed to H2S (less than or equal to 75 PPM) from day 6 of gestation until day 21 postpartum (PP) demonstrated normal reproductive parameters until parturition. At parturition, however, delivery time was extended in a dose dependent manner with a maximum increase of 42% at 75 PPM. Maternal liver cholesterol content was elevated significantly on day 21 postpartum following exposure to 75 PPM H2S each day for 6 weeks. Pups which were exposed in utero and neonatally to day 21 postpartum developed with a subtle decrease in time of ear detachment and hair development and with no other observed change in growth and development through day 21 postpartum. PMID- 2237926 TI - Subchronic inhalation of triethylamine vapor in Fischer-344 rats: organ system toxicity. AB - Male and female F-344 rats were exposed at 0, 25, or 247 ppm triethylamine (TEA) vapor, 6 hr per day, 5 days per week for up to 28 weeks in order to characterize the subchronic organ system toxicity. Rats were weighed biweekly and scheduled sacrifices were performed following about 30, 60, and 120 days of exposure. No statistically significant treatment-related effects on organ weights, hematology, clinical chemistry, or electrocardiographic indices were observed. Body weight gain was not affected by TEA treatment. No physiologic or pathologic evidence of cardiotoxicity was seen in rats exposed to either TEA concentration for up to 28 weeks. No gross or histopathologic lesions attributable to TEA exposure were noted in any of the organs examined, including the nasal passages. This latter finding is in marked contrast to previously reported findings from this laboratory in which squamous metaplasia, suppurative rhinitis, and lymphoid hyperplasia were found in the respiratory epithelium of F-344 rats exposed to the structurally related chemical, diethylamine, under the same conditions as this study (Lynch et al., 1986). PMID- 2237927 TI - Assessment of the delayed neurotoxicity of tributyl phosphate, tributoxyethyl phosphate, and dibutylphenyl phosphate. AB - There industrial organophosphorus compounds were tested for their ability to cause organophosphorus compound-induced delayed neurotoxicity (OPIDN) in the adult hen. The compounds tested were tributyl phosphate (TBP), tributoxyethyl phosphate (TBEP), and dibutylphenyl phosphate (DBPP). The acute oral LD50 of TBP and DBPP were estimated to be 1,863 and 1,500 mg/kg, respectively, and the dose equal to the LD50 was used as a test dose. The acute oral LD50 of TBEP was greater than 5,000 mg/kg and 5,000 mg/kg was used as a test dose. An oral dose of 750 mg tri-o-cresyl phosphate (TOCP) was used as a positive control. For the acute delayed neurotoxicity test, hens were given two test doses of the test materials 21 days apart and killed 21 days after the second dose. None of the hens given TBP, TBEP, or DBPP exhibited nerve damage or clinical signs which distinguished them from untreated control animals. A single dose of TOCP resulted in paralysis and a histopathological profile typical of a distal neuropathy. For the assay of the inhibition of esterases, hens were killed 24 hours after a single dose equal to the greater of either the LD50 or 5000 mg/kg. TOCP administration resulted in over 90% inhibition of brain neurotoxic esterase (NTE), but none of the other three compounds inhibited NTE to an extent (greater than 70%) which would be expected to result in OPIDN. Administration of TOCP, TBEP, or DBPP resulted in approximately a 70% decrease in plasma butyrylcholinesterase (BuChE) activity. TBP caused a 2-3 fold increase in BuChE activity. TBEP administration resulted in about 45% inhibition of acetycholinesterase (AChE) in brain. These results indicate that TBP, TBEP, and DBPP are all unlikely to cause OPIDN with any single sublethal dose. PMID- 2237928 TI - A promising indicator of neurobehavioral toxicity using the nematode Caenorhabditis elegans and computer tracking. AB - A promising screening test for neurotoxicity has been developed using a computer tracking system and a species of nematode, Caenorhabditis elegans. The animals are viewed in dark-field illumination by a video camera interfaced directly to a microcomputer. Several hundred nematodes are tracked simultaneously and rates of locomotion and frequency of change of direction are reported in real time. This system can rapidly obtain reliable data on a variety of behavioral parameters relating to locomotion and response to sensory stimulation. Initial testing has examined the effects of six chemicals on locomotion. Four metals (copper, beryllium, mercury, and lead) and two organophosphate pesticides (malathion and vapona) have been studied. Copper and beryllium were chosen as chemicals that have not been shown to be neurotoxins and the other four chemicals were chosen as substances known to be neurotoxins. Our findings indicate that the rate of movement of exposed nematodes compared to the rate of movement of vehicle controls may prove to be useful as an indicator of neurotoxicity. PMID- 2237929 TI - The reproductive and developmental toxicity of High Flash Aromatic Naphtha. AB - Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9 carbon aromatic molecules (C9 aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent--High Flash Aromatic Naphtha. A program was initiated to assess the toxicological properties of High Flash Aromatic Naphtha since there may be human exposure through inhalation or external body contact. The current study was conducted to assess the potential for developmental toxicity in the mouse and for reproductive toxicity in the rat. In the developmental toxicity study in CD-1 mice, exposure of dams by inhalation to near lethal levels (1500 ppm) resulted in fetal mortality, reduced weight, delayed ossification, and an increased incidence of cleft palate. At 500 ppm, a level at which maternal weight gain was slightly reduced, fetal weight gain was also reduced, but there was no other evidence of developmental effects. The lowest exposure level (100 ppm) did not cause any maternal or developmental toxicity. There was no consistent evidence of reproductive toxicity in rats, even at exposure levels which resulted in significantly reduced parental weight gain. In addition, when parental exposure was stopped on GD (gestation day) 20, birth weights as well as postnatal survival were generally similar to control values, even in the 1500 ppm exposure group. Postnatal weight gain was also similar to controls early in weaning, but, if maternal exposure was reinitiated, weight gain was reduced in the high exposure group. However, when exposure was continued until delivery, pups in the high exposure group exhibited reduced litter size, birth weight and poor survival. Thus it was likely that the reduction in fetal weight, seen in the developmental toxicity study in mice, was transient and had no postnatal consequences if maternal exposure was terminated at any time prior to delivery. PMID- 2237930 TI - An evaluation of the developmental toxicity of 2,4-pentanedione in the Fischer 344 rat by vapour exposure. AB - The developmental toxicity of 2,4-Pentanedione (2,4-PD; CAS No. 123-54-6), a widely used industrial chemical, was investigated by vapour exposure, because of its widespread use, and potential for human exposure. Timed-pregnant Fischer 344 rats were exposed on gestational days (gd) 6 to 15 inclusive to analytically measured concentrations (as mean +/- SD) of 53 +/- 1.6, 202 +/- 4.7 and 398 +/- 5.7 ppm 2,4-PD vapour. At sacrifice (gd 21) foetuses were examined for external, visceral and skeletal variations and malformations. There was no maternal mortality, and body weight was reduced only at 398 ppm. Histological examination of maternal brains from the 398 ppm group showed no abnormalities. No treatment related effects were seen on number of corpora lutea; total, nonviable or viable implants per litter; pre-or post-implantation losses; or foetal sex ratio. Reduced foetal body weight per litter was seen at 398 ppm (males and females and all foetuses) and 202 ppm (males and all foetuses). There was no concentration related, or statistically significant, increase in the incidence of individual malformations, malformations by category (external, visceral or skeletal), or total malformations. Partial foetal atelectasis was increased at 398 ppm, and the increased incidence of 17 skeletal variants (out of 79 observed) indicated a consistent pattern of foetotoxicity at 398 ppm. In summary, at 398 ppm there was maternal toxicity (reduced body weight) and foetotoxicity (reduced body weight and ossification) and at 202 ppm there was foetotoxicity (reduced body weight). Embryotoxicity or teratogenicity were not seen at any concentration. The no observable-effects concentration was 53 ppm for both maternal and developmental toxicity. PMID- 2237931 TI - A 90-day toxicity study of the effects of petroleum middle distillates on the skin of C3H mice. AB - Petroleum middle distillates (PMDs) elicit skin tumors in mouse epidermal carcinogenesis studies. The response is characterized by a long latency with only a small percentage of animals developing tumors. Although the carcinogenic activity of certain other petroleum hydrocarbons largely depends upon the presence of polycyclic aromatic hydrocarbons (PAHs), many PMDs contain relatively low concentrations of PAHs. PMDs are also irritating to mouse skin, and chronic irritation may be involved in the development of skin tumors. This study was conducted to investigate the patterns of cutaneous irritation elicited by topical application of PMDs having compositional differences. The three PMDs selected for study were a steam cracked gas oil (SCGO), a lightly refined paraffinic oil (LRPO), and a jet fuel (JF). Male C3H/HeNCr1BR mice (25/group) were treated topically (37.5 microliters 2x/week for 13 weeks) with 10%, 50% or 100% (undiluted) concentrations of each PMD. Catalytically cracked clarified oil (CCCO, 10%), a potent carcinogen to mouse skin, was also tested. The vehicle was a noncarcinogenic mineral oil with a viscosity of 90 SUS. Cutaneous changes were evaluated by gross observations and light microscopy. Cutaneous irritation was the only significant toxic response in this study. Neither the vehicle nor any of the 10% PMD concentrations produced significant cutaneous irritation. The 10% CCCO and 50% PMD treatments all elicited slight to moderate proliferative and inflammatory changes in mouse skin. Ulcers were also observed microscopically in mice treated with 10% CCCO and 50% SCGO. The 100% SCGO treatment produced evidence of necrosis on Days 1-7 but not later in the study despite continued treatment. In contrast, the irritating effects of 100% LRPO were not evident until 2-3 weeks of study, and at study completion were characterized by moderately severe inflammatory and proliferative changes. The effects of 100% JF were qualitatively similar to 100% LRPO but less marked. Thus, the SCGO caused a different pattern of cutaneous responses than either LRPO or JF. The possible relationships of these cutaneous changes to epidermal carcinogenesis are being studied further. PMID- 2237933 TI - The lawyer looks for an "expert" expert. PMID- 2237934 TI - 'In vitro immunotoxicology and immunopharmacology: studies on drugs of abuse' by R.M. Pillai and R.R. Watson. PMID- 2237932 TI - Enhanced arrhythmogenicity of Freon 113 by hypoxia in the perfused rat heart. AB - The interaction of Freon 113 (1,1,2-trichloro-1,2,2-trifluoroethane) and hypoxia on the heart conduction system was studied using electrocardiogram monitoring of isolated perfused rat hearts. Freon 113 (0.2 mM) alone elicited significant atrioventricular conduction delay (p less than 0.05) and heart rate decrease (p less than 0.01), which were significantly enhanced by hypoxia (75% oxygen decrease), for instance, resulting in 2:1 AV block. The data suggest that arrhythmogenicity of Freon 113 on the heart conduction system may be enhanced synergistically by hypoxia. PMID- 2237935 TI - In vitro immunotoxicology and immunopharmacology: studies on drugs of abuse. AB - The application of immunotoxicology to the toxicologic assessment of drugs of abuse is a field of increasing importance. Interest in the effects of drugs of abuse on the immune system has greatly increased as a result of the AIDS epidemic. If drugs of abuse compromise the immune system, their use may well become a predisposing factor in the development or enhancement of AIDS in high risk groups. Therefore development and validation of newer methods of assessment of immunotoxicology and their adaptation to routine analysis is an absolute necessity. An important feature in toxicology in general, and in immunotoxicology in particular, is the need to develop in vitro assessment systems. Recent research has provided newer models, data on correlations of immune function variables, and a better understanding of the biologic relevance of certain immune function parameters. This paper analyzes these features in relation to the role of drugs of abuse in the modulation and alteration of the immune system and reviews the various in vitro techniques that could be used to evaluate immunotoxicity. PMID- 2237936 TI - Covalent binding of o,p'-DDD in rabbit lung and isolated rabbit lung cells. AB - The irreversible binding of o,p'-DDD was examined in isolated lung cells, in lung microsomes and in vivo in male New Zealand White rabbits. Non-ciliated bronchiolar (Clara) cells had the highest capacity to bind o,p'-DDD, followed by alveolar type II cells. A fraction of mixed unidentified lung cells was also able to bind o,p'-DDD while no binding was observed in alveolar macrophages. The activation of o,p'-DDD was shown to be mediated by cytochrome P-450 in both lung microsomes and isolated lung cells. In vivo, the binding was preferentially localized in the lung alveolar and bronchiolar regions. The binding of o,p'-DDD observed in vivo may thus be caused by the capacity of several cell types to activate o,p'-DDD. PMID- 2237937 TI - Studies of the rad-equivalence of ethylene oxide in the presence and absence of 12-O-tetradecanoylphorbol-13-acetate (TPA) in C3H/10T1/2 cells. AB - Cell transformation in vitro of C3H/10T1/2 cells, using gamma-radiation and ethylene oxide (EtO), in both the absence and presence of the cancer promoter, 12 O-tetradecanoylphorbol-13-acetate (TPA), was studied. TPA promotes transformation of C3H/10T1/2 cells to the same extent. In the dose ranges studied the average enhancement of the transformation frequency was 2.4 and 2.5 for EtO and gamma radiation, respectively. The rad-equivalence of EtO in the presence of TPA was calculated to be 75 +/- 52 rad/mMh (95% confidence interval) which is consistent with the value 78 +/- 14 rad/mMh (95% confidence interval) obtained without TPA treatment. PMID- 2237939 TI - The effect of Biostim (RU-41740) on the expression of cytokine mRNAs in murine peritoneal macrophages in vitro. AB - The immunomodulatory agent Biostim (RU-41740) was investigated for its ability to induce the expression of cytokine mRNAs in murine peritoneal macrophages in vitro. Northern blot analysis showed that in quiescent macrophage populations, both IL-1 alpha and IL-1 beta mRNA levels were dramatically increased in response to 1 microgram/ml Biostim. Dot-blot analysis showed that in quiescent macrophage populations the expression of mRNAs for IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha could be elevated by concentrations of Biostim as low as 1-10 pg/ml, detectable after 3 h exposure. In parallel experiments LPS was effective only at the higher concentration of 10 ng/ml. Time-course analysis showed that the expression of these cytokine mRNAs was transient, peaking after 1-3 h; only transcripts of IL-1 beta were detectable after 23 h exposure. No effects were seen on the expression of actin, a high-turnover housekeeping gene. We propose that this type of analysis represents a sensitive, specific and reproducible method for assessing the ability of drugs and chemicals to modulate the expression of cytokines that play a pivotal role in the induction of the immune response. PMID- 2237938 TI - Regulation of polyamine biosynthesis by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AB - We have examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on tissue polyamine concentrations in CD1 mice. Two days after a low dose treatment with TCDD, polyamine content of the liver and thymus of treated mice showed a 49 82% decrease, but that of spleen was not affected. Based on this finding, we examined the role of alterations in polyamine levels in the toxicity of TCDD. We administered the polyamine biosynthetic inhibitor difluoromethylornithine (DFMO) to animals treated with a toxic dose of TCDD. DFMO dramatically increased the toxicity of TCDD as measured by mortality, ascites and changes in organ weights. In addition, administration of the polyamine putrescine was able to reduce the toxicity of TCDD. These results suggest that a decrease in polyamine concentrations in critical organs may play an important role in the toxic effects of TCDD. PMID- 2237940 TI - 1-Methyl-4-phenylpyridinium (MPP+) does not exhibit paraquat-like immunoreactivity. AB - The structural analogy of paraquat with 1-methyl-4-phenylpyridinium (MPP+) has been implied in the aetiology of Parkinson's disease. The cross-reactivity of MPP+ to a specific antibody to paraquat was assessed by radioimmunoassay and was found to be very low. The results suggest that this polyclonal paraquat antibody does not mimic the MPP+ receptor. PMID- 2237941 TI - Enhanced antibody production in W/Wv mice exposed to ozone. AB - To investigate the modulation of defense mechanisms by ozone (O3) exposure, mast cell-deficient WBB6F1-W/WV and normal WBB6F1(-)+/+ mice were continuously exposed to 0.8 ppm O3 for 7 days. Although no differences in weights of lung, thymus and spleen were shown between exposed and control W/WV mice, antibody response to sheep red blood cells (SRBC) in exposed W/WV mice was markedly enhanced compared to control W/WV mice. In normal +/+ mice O3 exposure induced an increase in lung weight but did not enhance antibody production. These studies suggest that the susceptibility of W/WV mice to O3 may be different from that of +/+ mice. PMID- 2237942 TI - Sex hormones and coronary disease: a review of the clinical studies. PMID- 2237943 TI - Transformation of epiandrosterone into 3-oxa-, 3-thia-, 3-selena-, and 3-aza-17 oxaandrostanes of the 5 alpha series based on beta-scission of alkoxyl radicals. AB - 3 beta-Hydroxy-5 alpha-androstan-17-one was transformed into 17-oxa-5 alpha androstan-3 beta-ol in five steps involving conversion of the 17-ketone via the corresponding lactol to its hypoiodite and thence a regioselective beta-scission under irradiation to give ring D seco iodoformate, from which the 17-oxasteroids were derived. Four bisheterosteroids 3,17-dioxa-5 alpha-androstane, 3-thia-17-oxa 5 alpha-androstane, 3-aza-17-oxa-5 alpha-androstane, and 3-selena-17-oxa-5 alpha androstane) were synthesized from 17-oxa-5 alpha-androstan-3 beta-ol via 5, 8, 8, and 9 steps, respectively, involving a second regioselective beta-scission of an alkoxyl radical as the key step. PMID- 2237944 TI - High ethanol consumption as risk factor for intracerebral hemorrhage in young and middle-aged people. AB - We examined the prevalence of high ethanol intake, hypertension, and other risk factors for intracerebral hemorrhage in a case-control study of 24 young and middle-aged patients with intracerebral hemorrhage. We recorded ethanol consumption, history of hypertension, liver disease, cigarette smoking, and mild or severe coagulation disorder in each case of intracerebral hemorrhage and in 48 control patients matched by sex and age. In univariate matched analyses, the frequencies of high ethanol intake (p = 0.009), hypertension (p = 0.05), and coagulation disorder (p = 0.05) were higher in the cases than in the controls. After controlling for possible confounding factors, we found that high ethanol intake and hypertension were the only independent risk factors for intracerebral hemorrhage (p = 0.02 and p = 0.05, respectively). The hemorrhagic lesion found in cases with a high ethanol intake tended to be located in the cerebral lobes (p = 0.01), contrasting with the typical basal ganglia location of hypertensive hematomas (p = 0.009). We conclude that chronic, high ethanol intake should be considered as an important risk factor for lobar hematomas in young and middle aged people. PMID- 2237945 TI - Stroke in systemic lupus erythematosus. AB - We investigated the clinical and pathologic characteristics of stroke in 234 patients with systemic lupus erythematosus. Thirteen patients (5.6%) developed cerebrovascular disease. Cerebral infarction was noted in eight, cerebral hemorrhage in two, and subarachnoid hemorrhage in three. In seven (54%) of these 13 patients, stroke occurred less than or equal to 5 years after systemic lupus erythematosus was diagnosed. Among the predisposing risk factors for stroke, hypertension was the most important. Lupus anticoagulant was detected in three (38%) and anticardiolipin antibody in three (43% of seven investigated) of the patients with infarction. Evaluation of the clinical manifestations and autoantibodies indicated that renal involvement and high titers of anti deoxyribonucleic acid antibody were more frequent in the stroke group than in the non-stroke group. Autopsy studies on six of the patients with stroke revealed small infarcts and hemorrhages in all, but in no case was true angiitis observed. Libman-Sacks endocarditis was found in two of the three patients with infarction. In conclusion, the important contributory factor to the development of stroke in patients with systemic lupus erythematosus is considered to be hypertension mediated by immunologic abnormalities. Antiphospholipid antibodies and Libman Sacks endocarditis are closely associated with occlusive cerebrovascular disease. PMID- 2237946 TI - Regression of intracardiac thrombus after embolic stroke. AB - Using two-dimensional echocardiography, we studied the pathophysiology of intracardiac thrombus regression accompanied by anticoagulant therapy in 82 consecutive patients with acute cardiogenic cerebral embolism. We noted intracardiac thrombus in 15 patients; nine of the 15 were started on anticoagulant therapy with warfarin potassium to maintain the prothrombin time between 2.5 and 3.5 (international normalized ratio). Serial two-dimensional echocardiograms were obtained for these nine patients before and after anticoagulation, with the plasma levels of fibrinopeptide A, fibrinopeptide B beta 15-42, and D-dimer measured at the same time. In eight of the nine patients the intracardiac thrombi gradually decreased in size while the plasma level of fibrinopeptide A fell to within the normal range and the plasma levels of fibrinopeptide B beta 15-42 and D-dimer remained above the normal ranges. In the other patient the thrombus disappeared, with embolization to the right arm immediately after starting anticoagulant therapy. Mobile or small thrombi regressed earlier than nonmobile or large ones. We conclude that regression of intracardiac thrombi after anticoagulation may be based on the relative predominance of plasma fibrinolytic activity over anticoagulation-inhibited thrombin activity. PMID- 2237947 TI - Surgical experience with cerebral amyloid angiopathy. AB - Cerebral amyloid angiopathy can present as lobar intracerebral hemorrhage in an elderly person, presumably due to increased fragility of the vessels affected by amyloid deposition. For this reason, patients presenting with intracerebral hemorrhage and suspected of having cerebral amyloid angiopathy have often been treated nonsurgically. Since 1983 we have evaluated 11 patients with cerebral amyloid angiopathy (nine women and two men, mean age 73 years) who have undergone either intracerebral hematoma evacuation or brain biopsy. Nine of the 11 patients presented with intracerebral hemorrhage, which was unilobar in three patients and multilobar in six and involved the parietal lobes seven times, the frontal lobes four times, the temporal lobes four times, and the occipital lobes twice. These nine patients underwent hematoma removal, with no cases of abnormal intraoperative bleeding or recurrent hemorrhage. Six patients improved neurologically, and two were unchanged after hematoma evacuation; the remaining patient had a fatal cardiopulmonary arrest during the immediate postoperative period. During follow-up in seven patients (median 11 months, range 1 week to 74 months) none experienced a recurrent intracerebral hemorrhage and four continued to improve. Two of the 11 patients had cerebral amyloid angiopathy diagnosed by brain biopsy as part of an evaluation for dementia, also without surgical complications. This series suggests that patients with cerebral amyloid angiopathy may safely undergo operative procedures, and patients presenting with intracerebral hemorrhage may show neurologic improvement following evacuation of the hematoma. PMID- 2237949 TI - Correlation of clinical and computed tomographic findings in stroke patients. AB - We evaluated the correlation between clinical features and computed tomographic findings in a prospective study of 1,191 consecutive patients with acute cerebrovascular disease seen during 1 year. In the 386 patients in whom symptoms and signs initially suggested a cerebrovascular disorder, computed tomography revealed a relevant lesion in 154 (hemorrhagic in 52 [33.8%], ischemic in 102 [66.2%]) and a significant nonstroke abnormality in 14 (3.1%). Among the remaining 805 patients with symptoms and signs suggesting some central nervous system disorder other than stroke, computed tomography revealed a cerebrovascular lesion in 38 (4.7%); 35 of these lesions were ischemic. The computed tomographic findings was compatible with the final clinical diagnosis in 192 (84.2%) of the 228 patients with lesions. In the entire sample of 1,191 patients, a cerebrovascular disorder would have been missed in 38 (3.2%) without computed tomography. On the other hand, computed tomography failed to visualize a cerebrovascular lesion in 40 patients in whom such a lesion was clinically obvious. Our results emphasize that both careful neurologic assessment and a policy of early computed tomography are of crucial importance in the diagnosis of stroke and for therapeutic considerations. PMID- 2237948 TI - Remote effect of deep-seated vascular brain lesions on cerebral blood flow. AB - We measured regional cerebral blood flow using the xenon-133 inhalation method, at approximately 1 month after onset, in 60 stroke patients who had no evidence of major carotid artery stenosis or occlusion. Their single lesions (43 infarcts and 17 hematomas) were located in the capsulothalamolenticular region, sparing the cortex. Hemispheric mean cerebral blood flow was reduced on the side of the lesion in 25 patients and on both sides in 20. Regional hypoperfusion was observed in 46 patients (ipsilaterally in 34, bilaterally in 10, and contralaterally in two). Regional hypoperfusion was observed most frequently in the frontal lobe, particularly in the motor and premotor cortices of the prerolandic area. The 46 patients with regional hypoperfusion were compared with the 14 patients without regional hypoperfusion, considering the size and location of the lesion as well as the functional and analytic motor performances. As a rule, the lesion was slightly smaller and more posterior and the functional (p less than 0.001) and analytic (p less than 0.05) motor performances were significantly better in the 14 patients without regional hypoperfusion. Since the xenon-133 inhalation method examines cortical blood flow, we can attribute blood flow reductions resulting from deep-seated lesions to a functional depression akin to diaschisis. Interpretation of the clinical consequences and pathogenesis of this phenomenon requires further sequential and pathologic studies. PMID- 2237950 TI - Ultrasonic evaluation of early carotid atherosclerosis. AB - We investigated the prevalence of carotid atherosclerosis, including mild early lesions, and its association with cervical bruits and various risk factors (age, male sex, hypertension, hyperlipidemia, diabetes mellitus, obesity, and cigarette smoking) in 232 consecutive Japanese patients. High-resolution real-time B-mode ultrasonography was performed to determine the extent of atherosclerosis, and it was quantified by using a scoring system. The prevalence of carotid atherosclerosis was 49%, 59%, and 41% in all 232 patients, the 100 symptomatic patients, and the 132 asymptomatic patients, respectively. Although carotid lesions were detected frequently (87%) in the 30 patients with cervical bruits, bruits were noted in only 30% of the 88 examined patients with carotid atherosclerosis. Independent risk factors for carotid atherosclerosis in these patients were found to be age, male sex, and hyperlipidemia; diabetes mellitus was a possible risk factor for carotid atherosclerosis. Our study did not show a close association between hypertension and carotid atherosclerosis, and this might be caused by the high prevalence of hypertension in our patients. Our findings suggest an increasing prevalence of carotid atherosclerosis in the Japanese, though this should be confirmed in a population-based study. Our study demonstrates the clinical usefulness of high-resolution B-mode ultrasonography for the evaluation of early carotid atherosclerosis. PMID- 2237951 TI - Effect of emitted power on waveform intensity in transcranial Doppler. AB - This study assesses the problem of transcranial Doppler recording failure and seeks to determine the extent to which this can be ameliorated by increased emitted power. We hypothesized that waveform intensity is directly related to the rate and quality of successful recording and may be compared quantitatively among groups of patients. Among a large group of patients recorded at 800 mW/cm2 emitted power, intensity was strongest in white men, weakest in black women, and intermediate in black men and white women. It declined with age in women of either race, but not in men of either race. Analysis of the effect of emitted power on intensity predicted that significant numbers of waveforms recorded at 800 mW/cm2 could not be recorded at the current clinical standards of 100 mW/cm2, the difference being most pronounced in elderly black women. Temporal bone window thickness measured in a series of adult cadaver skulls was least in white men, greatest in black women, and intermediate in black men and white women. The findings of this study support the hypothesis that temporal bone window thickness is an important determinant of recording difficulty and suggest that increased emitted power can significantly increase successful recording, particularly in black and elderly patients. Increased power alone, however, cannot completely solve the recording problem within safe limits. PMID- 2237952 TI - Correlates of middle cerebral artery blood velocity in the elderly. AB - We analyzed the association between hematologic factors and blood velocity of the middle cerebral artery in 42 healthy ambulatory subjects aged 63-86 years. We found a significant inverse association between mean velocity and both hematocrit (r = -0.37, p less than 0.02) and fibrinogen concentration (r = -0.42, p less than 0.005). These two variables are independently associated with velocity and together explain 29% of the variance in mean velocity. Both hematocrit and fibrinogen concentration should be considered in the interpretation of transcranial Doppler findings in this population. PMID- 2237953 TI - Comparison of transcranial and cervical continuous-wave Doppler in the evaluation of intracranial collateral circulation. AB - Adequate intracranial collateral circulation reduces risk of stroke in carotid artery surgery. To evaluate their relative accuracies in assessing intracranial collateral blood flow, we prospectively compared transcranial Doppler and continuous-wave Doppler of the cervical carotid arteries combined with compression of the common carotid artery in 28 consecutive patients before carotid endarterectomy. Ten healthy volunteers served as controls. Three patients (11%) were excluded from compression of arteries because of diffuse disease in the common carotid artery. A total of 199 compressions were performed without complications. Lack of a suitable transtemporal window precluded the performance of transcranial Doppler in three patients (12%). The anterior communicating artery was identified in all the normal volunteers and 80% of patients by both methods. The posterior communicating artery was identified by both methods in 16 of 20 attempts in controls. Continuous-wave Doppler identified the posterior communicating artery in 30 of 50 attempts in patients; transcranial Doppler identified the posterior communicating artery in 20 of 44 attempts in patients (p greater than 0.5). Detection of intracranial collaterals correlated with intraoperative carotid artery back pressure measurements in 23 of 25 patients (92%). We conclude that continuous-wave Doppler of the extracranial arteries combined with common carotid artery compression is a safe and easy way to detect intracranial collaterals, with an accuracy equivalent to transcranial Doppler. PMID- 2237954 TI - Moderate hypothermia after cardiac arrest of 17 minutes in dogs. Effect on cerebral and cardiac outcome. AB - Moderate hypothermia (30 degrees C) induced before circulatory arrest is known to improve neurologic outcome. We explored, for the first time in a reproducible dog outcome model, moderate hypothermia induced during reperfusion after cardiac arrest (resuscitation). In three groups of six dogs each (N = 18), normothermic ventricular fibrillation cardiac arrest (no blood flow) of 17 minutes was reversed by cardiopulmonary bypass--normothermic in control group I (37.5 degrees C) and hypothermic to 3 hours in groups II (32 degrees C) and III (28 degrees C). Defibrillation was achieved in less than or equal to 5 minutes and partial bypass was continued to 4 hours, controlled ventilation to 20 hours, and intensive care to 96 hours. All 18 dogs survived. Electroencephalographic activity returned significantly earlier in groups II and III. Mean +/- SD best neurologic deficit between 48 and 96 hours was 44 +/- 8% in group I, 38 +/- 12% in group II, and 35 +/- 7% in group III (differences not significant). Best overall performance category 2 (good outcome) between 48 and 96 hours was achieved in none of the six dogs in group I and in four of the 12 dogs in the combined hypothermic groups II and III (difference not significant). Mean +/- SD brain total histologic damage score was 130 +/- 22 in group I, 93 +/- 28 in group II (p = 0.05), and 80 +/- 26 in group III (p = 0.03). Gross myocardial damage was greater in groups II and III than in group I--numerically higher overall and significantly higher in group III for the right ventricle alone (p = 0.02). Moderate hypothermia after prolonged cardiac arrest may or may not improve cerebral outcome slightly and can worsen myocardial damage. PMID- 2237955 TI - Protective effects of a monosialoganglioside derivative following transitory forebrain ischemia in rats. AB - We evaluated the effects of treatment with the inner ester derivative of the monosialoganglioside GM1 on cortical electroencephalographic activity and hippocampal CA1 morphology after transitory, near-complete cerebral ischemia in rats. Ischemia was induced by the four-vessel occlusion method, and we studied only the 58 rats that showed flattening of the cortical electroencephalogram for the entire 30 minutes of occlusion. The ganglioside (n = 30) or saline (n = 28) was administered intravenously immediately after release of the carotid clips and then intramuscularly for 21 days of observation. Cortical electroencephalographic activity was monitored throughout the experiment. After 21 days of recirculation we assessed hippocampal CA1 damage by light microscopy. The results indicate that treatment with the ganglioside reduces postischemic secondary damage to the cortical circuitry (as indicated by significantly higher cortical electroencephalographic activity late after reperfusion) and limits neuronal loss in the CA1 region. Our results lend support to the possible therapeutic use of ganglioside in human pathologic conditions associated with cerebrovascular insufficiencies. PMID- 2237956 TI - Effect of ischemia induced by middle cerebral artery occlusion on superoxide dismutase activity in rat brain. AB - Acute cerebral ischemia increases the generation of free radicals, causing cell damage, and theoretically may decrease the activity of the scavenging enzyme superoxide dismutase. To investigate the role of superoxide dismutase in cerebral ischemia, we used a model of middle cerebral artery occlusion in rats. In this model an infarct is produced in the pyriform and frontoparietal cortices, extending into the lateral basal ganglia. We measured superoxide dismutase activity by using the xanthine oxidase cytochrome c reduction assay in these areas of rat brains. Tissue samples were analyzed 20 minutes, 2, 6, or 24 hours, or 7 days after middle cerebral artery occlusion and 2 or 24 hours or 7 days after sham operation (n = 8-10 at each time). There was no significant change in superoxide dismutase activity relative to control values in any brain area at any time up to 24 hours after surgery. However, 7 days after middle cerebral artery occlusion a significant decline in superoxide dismutase activity, to 55%-68% (p less than 0.05) of that in unoperated controls, was observed in all brain areas. Our results do not support an important role for changes in the activity of endogenous superoxide dismutase during the acute phase of cerebral ischemia. However, the decrease in superoxide dismutase activity 7 days after ischemia could indicate ongoing additional damage to peri-infarct tissue. PMID- 2237957 TI - Progressing cerebral infarction in relation to plasma glucose in gerbils. AB - We studied neurologic morbidity and its evolution during hyperglycemia induced immediately after permanent unilateral common carotid artery ligation in Mongolian gerbils. A total of 60 animals were divided into five groups: one experiencing severe hyperglycemia for 1 hour after the onset of ischemia (brief hyperglycemia group, n = 13), a normoglycemic control group for the brief hyperglycemia group (n = 12), a group with severe hyperglycemia for 4 hours after the onset of ischemia (prolonged hyperglycemia group, n = 11), a normoglycemic control group for the prolonged hyperglycemia group (n = 13), and a hyperosmolar normoglycemic control group for the prolonged hyperglycemia group (n = 11). Neurologic morbidity and mortality were higher in the two hyperglycemic groups than in the three normoglycemic control groups. The neurologic deficit progressed according to the duration of severe hyperglycemia. In the three normoglycemic control groups neurologic status stabilized 120 minutes after the onset of ischemia, in the brief hyperglycemia group stabilization occurred at 210 minutes, and in the prolonged hyperglycemia group neurologic deficit progressed for approximately 360 minutes, coinciding with the death of all but one gerbil, in which the neurologic deficit remained stable until death 23 hours after ischemia. We suggest that hyperglycemia is another cause of progressing cerebral infarction. PMID- 2237958 TI - Giant basilar aneurysm in the course of subacute bacterial endocarditis. AB - We describe a man aged 42 years with mitral valve regurgitation who suffered from subacute bacterial endocarditis caused by Streptococcus morbillorum. The clinical picture began with a toxic syndrome. Five months later, the patient had an embolic episode and a right rostral pontine stroke, which was followed a few days later by an adversive focal seizure on the right. Despite antibiotic treatment, he suffered complete third nerve palsy. Arteriography, magnetic resonance imaging, and computed tomography of the brain showed a giant aneurysm in the rostral end of the basilar artery; the aneurysm was clipped. We discuss the clinical features, radiology, and characteristics of this aneurysm as a unique case of a giant bacterial aneurysm in the vertebrobasilar system. PMID- 2237959 TI - Rebleeding from intracranial dissecting aneurysm in the vertebral artery. AB - We describe two patients with rebleeding from intracranial vertebral artery dissecting aneurysms during the acute stage. One patient had excellent results after emergency surgery. A review of recent reports including 60 patients with this disorder revealed a rebleeding rate of 30%, mostly during the acute stage. This suggests that a ruptured dissecting aneurysm in the vertebral artery is at risk for rebleeding during the acute stage, similar to a saccular aneurysm in the same location. PMID- 2237960 TI - Embolic stroke after smoking "crack" cocaine. AB - A 39-year-old woman had an embolic upper division middle cerebral artery branch occlusion 3 hours after smoking the free base of cocaine ("crack"). Radionuclide ventriculography demonstrated cardiomyopathy, and echocardiography documented a left atrial thrombus. This case demonstrates that embolism is one mechanism of ischemic stroke after cocaine use, and that cardiomyopathy, possibly cocaine induced, may be the source of embolus. A cardiac source of embolus should be sought in patients with cocaine-associated cerebral infarction. PMID- 2237961 TI - Restorative neurology. Drugs and recovery following stroke. PMID- 2237962 TI - Ephedrine-induced intracerebral hemorrhage and central nervous system vasculitis. PMID- 2237963 TI - Pulmonary arteriovenous fistulas are at high neurologic risk. PMID- 2237964 TI - Effect of hyperoxia differs during ischemia and reperfusion. PMID- 2237965 TI - Predisposing factors in cardiogenic cerebral embolism. PMID- 2237966 TI - Cerebrovascular diseases--seventeenth Princeton Conference. Durham, North Carolina, March 16-18, 1990. Proceedings. PMID- 2237967 TI - Protein phosphorylation during ischemia. AB - Many investigations have shown that calcium and adenosine triphosphate are crucial to central nervous system functions. It is probable that alterations of these substances during central nervous system ischemia are involved in the processes that cause irreversible neural damage. Calcium regulates several protein kinases that are responsible for phosphorylation of proteins vital for many central nervous system functions. Using a rabbit spinal cord ischemia model, we found protein kinase C and calcium/calmodulin-dependent kinase were severely affected during the first hour of ischemia. Protein kinase A was not significantly affected. The time course of lost protein kinase C enzyme activity closely corresponded to irreversible loss of neurologic function, and there is evidence that protein kinase C inhibitor activity is generated. Also, drugs that inhibit protein kinase C increased neurologic damage when administered during the early phases of ischemia. These results suggest that protein phosphorylation, particularly by protein kinase C, is critical to maintenance of neurologic function. PMID- 2237968 TI - Progress report of the Stroke Prevention in Atrial Fibrillation Study. AB - The Stroke Prevention in Atrial Fibrillation Study recently found and reported (SPAF Investigators, N Engl J Med, 1990;322:863-868) a beneficial effect of both warfarin and aspirin compared with placebo in the primary prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Among warfarin-eligible patients, the event rates were 1.6%/yr for those receiving active antithrombotic therapy (warfarin or aspirin) and 8.3%/yr for those receiving placebo (p less than 0.00005) (risk reduction 81%, 95% confidence interval 56-91). Ironically, we did not find a beneficial effect of aspirin in warfarin-ineligible patients. On the basis of these results, the study has been reshaped to directly compare these two antithrombotic agents. Insight into the apparent aspirin unresponsiveness noted in some patients also is being sought. Interpretation of the preliminary results and the reshaping of the study have been made more complex by the continued blinding of the investigators to certain portions of the data. Presented is an account of the study from its inception through its recent redesign. PMID- 2237969 TI - Growth factor expression after stroke. AB - Fibroblast growth factors are polypeptides with potent trophic effects on central nervous system cells. Both acidic and basic forms of fibroblast growth factor are found in the mammalian brain. We have examined the expression of these factors after focal brain injury or stroke. After infarction of the lateral cerebral cortex in the mature rat brain, we found a twofold to threefold increase during the first 3 weeks after stroke in levels of fibroblast growth factors in tissue surrounding infarcts. This increase persisted for at least 2 months and appeared mainly to be due to increased levels of basic, but not acidic, fibroblast growth factor. Because of its gliotrophic, angiogenic, and neuronotrophic properties, basic fibroblast growth factor may play an important role in the cascade of cellular reactions that contributes to wound healing and functional recovery after stroke. PMID- 2237970 TI - Genetics of cerebrovascular disease. AB - Stroke is a complex disease, with both genetic and environmental factors having a role in its pathogenesis. A review of past studies shows some evidence of genetic influences in the development of stroke. This is supported by studies of cardiovascular disease, which indicate major genetic influences at several levels including the development of risk factors. New approaches to phenotypic classifications, patient ascertainment, and genetic analysis will stimulate research into the role of genetics in cerebrovascular disease. PMID- 2237971 TI - Modification of stroke susceptibility by genotype-dependent maternal influences. AB - The influence of the prenatal and postnatal maternal environment on stroke susceptibility was evaluated by reciprocally crossing the spontaneously hypertensive (SHR) and the Dahl salt-sensitive (SS/Jr) inbred rat strains to produce reciprocal F1 hybrids that were nurtured, respectively, during prenatal and postnatal life by SHR or SS/Jr mothers. Following placement on a high-salt diet containing 8% NaCl at 35 days of age, F1 rats reared by SHR mothers had shorter survival times and were more likely to die with cerebral hemorrhage than F1s reared by SS/Jrs. Across reciprocal F1 female groups, enhanced susceptibility to stroke was associated with greater elevations of systolic blood pressure, but this association was not seen across reciprocal F1 male groups. There was also an association between blood pressure and stroke within each F1/gender subgroup: Rats eventually suffering strokes developed higher blood pressure after placement on the high-salt diet than rats that did not suffer stroke. Lower day 35 body weights (before exposure to the high-salt diet) were associated with greater likelihood of stroke both across the reciprocal F1 groups, and within three of the four F1/gender subgroups. The differences in stroke susceptibility between the reciprocal F1 groupings may be due to systematic differences in the prenatal and/or postnatal environments of SHR and SS/Jr mothers and may be mediated by variations in the nutritive capacity of the two inbred mothers. PMID- 2237972 TI - Multilevel transneuronal degeneration after brain damage. Behavioral events and effects of anticonvulsant gamma-aminobutyric acid-related drugs. AB - Recent morphologic and behavioral studies of the effects of gamma-aminobutyric acid agents on transsynaptic degeneration after cortical and striatal damage are reviewed and discussed. Following unilateral lesions of the anteromedial cortex, mild atrophy appears in the ipsilateral striatum and substantia nigra pars reticulata. Long-term diazepam administration greatly enhances this degeneration, extends the degeneration into the thalamus, and severely disrupts recovery from somatosensory asymmetries. Following unilateral excitotoxic lesions of the striatum, progressive degeneration of neurons occurs in the substantia nigra pars reticulata and efferent targets in the thalamus. This degeneration can be prevented by chronic infusion of muscimol, a gamma-aminobutyric acid agonist. Unexpectedly, this treatment did not facilitate recovery from somatosensory asymmetries. Recovery in muscimol-treated animals was impaired relative to saline treated controls. Thus, gamma-aminobutyric acid agonists either may enhance or prevent neural atrophy secondary to brain damage, but the behavioral outcome appears to depend importantly on the excitatory and inhibitory characteristics of the affected networks. PMID- 2237973 TI - Influence of amphetamine treatment on somatosensory function of the normal and infarcted rat brain. AB - The consequences of acute amphetamine administration on the metabolic responsiveness of the cerebral cortex to physiologic activation were studied in normal and infarcted rats. Treated rats received a 4 mg/kg intravenous injection of d-amphetamine 1 hour before unilateral vibrissae stimulation and 2 deoxyglucose study. In nontreated normal rats, metabolic activation was restricted to the major relay stations of the vibrissae-barrel circuit. In amphetamine-treated rats, stimulation-induced increased glucose utilization was widespread, including ipsilateral and contralateral cortical regions outside the barrel field circuit. For example, an 84% increase in glucose utilization above control was seen in cortical areas anterior to the barrel field region. Increased glucose utilization induced by stimulation was severely depressed in nontreated rats that had undergone infarction of the left cortical barrel field 2 weeks previously. Vibrissae stimulation failed to increase glucose utilization significantly in cortical areas remote from the infarct. In contrast, bilateral increases in glucose utilization were observed within cortical regions of treated infarcted rats. For example, a 50% increase in glucose utilization was detected in cortical areas bordering the infarct. Thus, in the normal and infarcted rat, amphetamine appears to promote alternate circuit activation--a pharmacologic property that may be advantageous for recovery after injury. PMID- 2237974 TI - Effects of MK-801 on recovery from sensorimotor cortex lesions. AB - Histologic evidence suggests that drugs acting as noncompetitive antagonists at the N-methyl-D-aspartate receptor can have beneficial or pathologic effects on central nervous system neurons. In the present experiments we examined the effects of MK-801 on recovery of behavioral function after unilateral lesions in the rat somatic sensorimotor cortex. In the first experiment, rats with unilateral sensorimotor cortex lesions were given either MK-801 (1 mg/kg) or saline 12-16 hours after surgery. Additional injections were given on postoperative days 2, 4, and 6. Behavioral tests measured somatosensory asymmetries (i.e., bilateral tactile stimulation tests) and forelimb placing. After creation of sensorimotor cortex lesions, rats showed an ipsilateral somatosensory bias and an impairment in placing the contralateral forelimb. Rats treated with MK-801 recovered slightly faster than saline-treated animals as measured by a bilateral tactile stimulation test (p less than 0.05). In contrast, there was no significant difference between the groups in the recovery of forelimb placing. In a second experiment, rats with sensorimotor cortex lesions were treated with a single injection of MK-801 after behavioral recovery. Twenty hours after the MK-801 injection, rats with sensorimotor cortex lesions showed a reinstatement of the placing deficits. The impairment endured for at least 7 days after injection. These behavioral data support the idea that MK-801 can have either beneficial or detrimental effects when administered after brain damage. PMID- 2237975 TI - Ionic channels, cholinergic mechanisms, and recovery of sensorimotor function after neocortical infarcts in rats. AB - Unilateral photochemical infarcts were produced in the hind limb sensorimotor neocortex of 243 rats by intravenous injection of the fluorescein derivative Rose Bengal and focal illumination of the intact skull surface. Facial contact stimuli governed the degree and recovery rate of contralateral tactile/proprioceptive forelimb placing reactions. Contralateral forelimb placing recovered, whereas hind limb placing was resistant to recovery. Infarcted rats displayed marked recovery of spontaneous limb usage (beam traversing). However, deficits in isolated tactile/proprioceptive hind limb placing reactions endured. Posttreatment with the class IV calcium antagonist flunarizine after neocortical infarction protected sensorimotor function in a dose-dependent manner. This protective effect may be due to the peculiar ionic channel blocking profile of flunarizine. Scopolamine hydrobromide reinstated contralateral placing errors in infarcted rats at a dosage that did not affect neurologically intact rats. The cognitive enhancer sabeluzole, a novel benzothiazol derivative, dose-dependently blocked the anticholinergic-induced deterioration of a sensorimotor deficit in rats. PMID- 2237976 TI - Brain natriuretic peptide-like immunoreactive innervation of the cerebrovascular system in the rat. AB - Brain natriuretic peptide is a recently discovered neuropeptide. We used an antiserum against porcine brain natriuretic peptide to identify a system of immunoreactive innervation of the cerebrovascular tree in the rat. The internal carotid artery and the proximal portions of the middle and anterior cerebral and posterior communicating arteries were the most intensely innervated by immunoreactive fibers. The density of innervation decreased distally along the anterior, middle, and posterior cerebral arteries and the basilar and vertebral arteries. Brain natriuretic peptide and the related atrial natriuretic peptide are known to cause dilatation of cerebral arteries. Our findings suggest that brain natriuretic peptide may serve as a vasodilatory neuromodulator in the cerebral circulation. PMID- 2237977 TI - Neurogenic control of the cerebral circulation during global ischemia. AB - The influence of the trigeminal nerve on the cerebral circulation was investigated in chronically denervated cats during and after reversible four vessel occlusion for 10 minutes combined with controlled hypotension (50 mm Hg). Postocclusive hyperemia 30 minutes after reperfusion was attenuated by up to 48% in cortical gray matter of the anterior, middle, and posterior cerebral artery territories on the side of trigeminal ganglionectomy. Similar results were observed for denervation accomplished by direct surgical ablation and by the topical application of capsaicin to a cortical branch of the middle cerebral artery. Denervation did not alter basal cerebral blood flow or the duration of hyperemia, nor did it impair the cerebrovascular response to hypercapnia. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion and suggest that strategies directed at blocking axon reflex-like mechanisms may be beneficial in reducing the morbidity that follows severe cortical hyperemia. PMID- 2237978 TI - Magnetic resonance imaging demonstrates that electric stimulation of cerebellar fastigial nucleus reduces cerebral infarction in rats. AB - We sought to determine whether high spatial resolution magnetic resonance imaging is useful for noninvasive quantitation of the ischemic infarct produced by occlusion of the middle cerebral artery and for detection of reduced infarct volume elicited by electric stimulation of the cerebellar fastigial nucleus. Male rats of the spontaneously hypertensive strain were anesthetized, the middle cerebral artery was occluded, and the fastigial nucleus was stimulated for 1 hour. Twenty-four hours later, rats were reanesthetized and T1- and T2-weighted images were obtained. Rats were killed and the volume and distribution of the lesion was established by histopathology. Magnetic resonance imaging estimates of the lesion volume were 271 +/- 41.0 mm3 (middle cerebral artery, n = 5) and 148 +/- 8.4 mm3 (middle cerebral artery + fastigial nucleus stimulation, n = 6; 45% reduction, p less than 0.05). Histopathological analysis revealed a lesion of 229.8 +/- 15.4 mm3 involving somatosensory cortex, lateral caudate putamen, and lateral hippocampus. Fastigial nucleus stimulation resulted in a 36% reduction in infarct volume to 146.0 +/- 10.3 mm3. The retrieved zone was largely in the cortex dorsal and ventral to the lesion and mostly posterior to the lesion. The estimates of lesion volume by magnetic resonance imaging and histopathology did not differ and were highly correlated (r = 0.90; p less than 0.001). This study confirms our previous finding that fastigial nucleus stimulation reduces the volume of a focal ischemic infarct and demonstrates that magnetic resonance imaging not only accurately estimates the volume of the lesion but also can detect changes as small as 50-100 mm3. PMID- 2237979 TI - Spreading depression-like depolarization and selective vulnerability of neurons. A brief review. AB - If oxygen is withdrawn from rat hippocampal slices, a spreading depression-like response occurs earlier and is of larger amplitude in the CA1 area than in the dentate gyrus. After reoxygenation, recovery of synaptic transmission correlates inversely with the time spent in spreading depression. Recovery occurs more frequently in dentate gyrus than in CA1. Chlorpromazine and the gangliosides GM1 and AGF2 promote recovery from hypoxic depression of synaptic transmission in CA1. Prevention of irreversible loss of function correlates closely with a shortening of the time spent in spreading depression. If Ca2+ is withdrawn before hypoxia, then synaptic function recovers upon restoration of oxygen and [Ca2+]o, despite prolonged spreading depression. When spreading depression lasting more than 6-9 minutes is induced in fully oxygenated slices by superfusion with high K+ solution, then transient recovery is followed by long-lasting loss of synaptic function. In intact brain of anesthetized rats, synaptic transmission in CA1 recovers after spreading depression-like depolarization lasting more than 30 minutes, but is lost irreversibly after 60 minutes. We conclude that entry of Ca2+ into neurons caused by spreading depression-like depolarization is important in the selective vulnerability of neurons; the duration of depolarization is critical to cell survival; and in the presence of a normal blood supply, neurons resist protracted spreading depression-like depolarization. PMID- 2237980 TI - Ionic concomitants of astroglial transformation to reactive species. AB - Brain injury, including ischemia, changes normal astrocytes into reactive species that hypertrophy and begin to proliferate. Understanding the mechanisms that underlie these changes could lead to new abilities to promote regeneration and retard neural degeneration after ischemia. Because ionic changes occur after nonneural cells are exposed to mitogens, we have begun to examine the ionic changes that may trigger reactive gliosis. We showed that two changes thought to be important for mitogenesis, elevation of interstitial potassium or intracellular pH, are correlated with reactive gliosis as indicated by increased immunohistochemical staining for glial fibrillary acidic protein. This relation was seen after activation of cerebral cortex by recurrent spreading depression but not by physiologic stimulation. Deoxyribonucleic acid synthesis occurs in fibroblasts only when intracellular potassium exceeds 90 mM, a level seen in astrocytes only during spreading depression. Thus, our results support the contention that a threshold level of potassium (and pH) must be exceeded in eukaryotic cells before proliferation or anabolism will proceed. PMID- 2237981 TI - Symptomatic carotid endarterectomy trials. AB - The possible benefit of carotid endarterectomy in stroke prevention is being evaluated in three major clinical trials. To date, the European Carotid Surgery Trial has randomized 2,200 patients, 30% of whom have a carotid stenosis of greater than 70% appropriate to their symptoms. The North American Symptomatic Carotid Endarterectomy Trial has randomized 1,000 patients, of whom more than half have this severity of appropriate stenosis. Quality control and the evaluation of outcome events in this trial is achieved by a three-tier review, including review by medical and surgical adjudicators who are blinded to the treatment arm of each patient. Baseline characteristics of the patients eligible but not randomized are similar to those of patients who have been randomized. Two percent of the patients randomized to the surgical arm have declined surgery and crossed over to the medical arm, and 3% have elected surgery after randomization to the medical arm. Both of these studies, as well as a Veterans Administration trial, are continuing to randomize patients. PMID- 2237982 TI - Neuronal protection correlates with prevention of calcium-calmodulin binding in rats. AB - We correlated the efficacy of several clinically relevant pharmacotherapies with their ability to prevent calcium influx into neurons and subsequent binding to calmodulin. We studied the administration of CGS 19755, nimodipine, nicardipine, and combinations of these drugs before or immediately after ischemia in globally ischemic rats. Calcium-calmodulin binding was graded by an immunohistochemical assay after 2 and 24 hours of reperfusion (n = 5-6 at each time period), and histologic damage was graded by light microscopy after 72 hours of reperfusion (n = 6). Calcium-calmodulin binding correlated with the severity of delayed histologic damage in various brain regions. In untreated ischemic control rats, marked calcium-calmodulin binding was seen in CA1 and CA3 after 24 hours of reperfusion (p less than or equal to 0.01). Administered before ischemia, CGS 19755 prevented calcium-calmodulin binding across all brain regions after 2 and 24 hours of reperfusion compared with controls (p less than or equal to 0.05). This effect was most prominent in CA3 and CA1, where the drug also reduced delayed neuronal damage (p less than or equal to 0.05). Lower doses or postischemic administration of CGS 19755, nimodipine, nicardipine, and a combination of postischemic CGS 19755 and nicardipine had a more limited effect on calcium-calmodulin binding and did not protect against delayed neuronal damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237983 TI - N-methyl-D-aspartate and non-N-methyl-D-aspartate antagonists in global cerebral ischemia. AB - The hippocampal lesion induced by cerebral ischemia has several excitotoxic features. Denervation of the ischemia-vulnerable pyramidal cells has a protective effect. Because most synapses are glutamatergic, administration of glutamate antagonists after ischemia also could be protective. Growing evidence now indicates that non-N-methyl-D-aspartate antagonists are more effective than N methyl-D-aspartate antagonists in complete global ischemia. One explanation offered is that ischemia may sensitize pyramidal neurons so that "normal" postischemic synaptic activity induces lethal damage. PMID- 2237984 TI - Ischemia induces release of glutamate in regions spared from histopathologic damage in the rat. AB - Excessive release of glutamate is thought to play a major role in the susceptibility of neurons to ischemia. In the present study, we evaluated whether differences in the magnitude of glutamate release resulted in some regions being vulnerable to ischemia, but others being spared from irreversible histopathologic damage. Specifically, we compared the temporal profile of ischemia-induced changes in extracellular levels of glutamate in a region selectively vulnerable to 10 minutes of transient ischemia (CA1 sector of the hippocampus) to the changes occurring in regions that, although rendered ischemic, are usually unaffected by a 10-minute insult (i.e., thalamus, cortex, and dorsolateral striatum). In an attempt to correlate the regional changes in glutamate release to the magnitude of the ischemic insult, the degree of ischemia (e.g., ATP depletion, lactate accumulation, and local cerebral blood flow reduction) and the final histopathologic outcome were also evaluated in these regions. Blood flow reduction and energy depletion were severe and uniform in all regions. However, the histopathologic outcome illustrated a different pattern. Although the CA1 sector of the hippocampus was severely damaged, all other brain regions were unaffected by the 10-minute insult. Extracellular glutamate levels, measured by microdialysis, were significantly elevated during ischemia in all four regions. These levels continued to increase during the early recirculation period and gradually returned to baseline by 30 minutes of reperfusion, with a similar temporal changes in all four brain structures. These results, taken with our previous findings, demonstrate that elevated intraischemic glutamate levels are insufficient to independently engender ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237985 TI - Comparison of phenytoin with noncompetitive N-methyl-D-aspartate antagonists in a model of focal brain ischemia in rat. AB - Recent in vitro and in vivo experiments have suggested that excitatory amino acid antagonists, particularly those active at the N-methyl-D-aspartate receptor subtype, are effective in ameliorating ischemic injury due to their antiexcitotoxic activity. However, these drugs are also potent and effective in vivo anticonvulsants. The present experiments compared the noncompetitive N methyl-D-aspartate antagonists phencyclidine and MK-801 with the anticonvulsant phenytoin in a model of focal brain ischemia. Fisher F-344 rats were subjected to tandem occlusion of the middle cerebral and ipsilateral common carotid arteries under halothane anesthesia. Compounds were administered intravenously 30 minutes and 24 hours after arterial occlusion; infarct size was assessed at 48 hours after occlusion. Phencyclidine had no effect on infarct volume at 1 mg/kg, significantly reduced (by 36%) infarct volume at 3 mg/kg, and produced a nonsignificant 26% decrease at 10 mg/kg. The more potent and selective noncompetitive antagonist MK-801 reduced (by 32%) infarct volume significantly at 0.1 mg/kg, produced a nonsignificant 23% decrease at 0.3 mg/kg, and had no effect at 0.5 mg/kg. Phenytoin, which is not a glutamate antagonist, reduced the infarct volume by 45% at 28 mg/kg. A single dose of phenytoin (28 mg/kg) administered 30 minutes after occlusion was neuroprotective, but delaying drug administration for more than 2 hours was ineffective. These data suggest that blockade of the N methyl-D-aspartate receptor is effective in reducing the infarct size after focal cerebral ischemia. The neuroprotective activity of phenytoin suggests that this may be related to the common anticonvulsant action. PMID- 2237986 TI - The pathophysiology of anoxic injury in central nervous system white matter. AB - White matter of the mammalian brain is susceptible to anoxic injury, but little is known about the pathophysiology of this process. We studied the mechanisms of anoxic injury in white matter using the isolated rat optic nerve, a typical central nervous system white-matter tract. Optic nerve function, measured as the area under the compound action potential, rapidly failed when exposed to anoxia. Postanoxic recovery was variable, depending on duration of the anoxic insult; after a standard 60-minute period of anoxia, the compound action potential recovered to 28.5% of control. Irreversible anoxic injury was critically dependent on extracellular Ca2+; maintaining the tissue in zero [Ca2+] solution throughout the anoxic period resulted in 100% compound action potential recovery. Increasing perfusate [Ca2+] during anoxia from zero to 4 mM resulted in progressively less recovery. Anoxic damage to the optic nerve appears to depend on the gradual accumulation (over tens of minutes) of Ca2+ in a cytoplasmic compartment. The inorganic Ca2+ channel blockers Mn2+ (1 mM), Co2+ (1 mM), or La3+ (0.1 mM) had no effect on recovery of the compound action potential after anoxia; only Mg2+ (10 mM) significantly improved recovery. Treatment with the dihydropyridine Ca2+ channel blockers nifedipine (1-10 microM) or nimodipine (1 40 microM) also had no effect on recovery from anoxia. Thus, Ca2+ influx during anoxia does not occur via conventional Ca2+ channels. Preliminary evidence suggests that this Ca2+ influx may occur via other cation channels that are imperfectly selective for Ca2+ or via the Na(+)-Ca2+ exchanger.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2237987 TI - Putative neuroexcitation in cerebral ischemia and brain injury. AB - Involvement of neuroexcitatory mechanisms in cerebral ischemia and brain injury was explored in experimental models of repetitive forebrain ischemia by temporary occlusion of carotid arteries in gerbils and cryogenic injury to the cerebral cortex in rats and gerbils. Our observations in these models revealed a pattern of injury that involved some anatomic structures outside the areas of direct ischemic or traumatic insult. Such foci of injury revealed conspicuously abnormal uptake of 45Ca associated with slight or moderate neuronal alteration, whereas severely injured areas showed no 45Ca uptake. Electron microscopic observations revealed a characteristic presence of calcium in swollen dendrites, closely resembling pictures obtained in neuroexcitatory conditions such as epileptic seizures. Abnormal uptake of 45Ca was associated with apparent blood-brain barrier changes characterized by intracytoplasmic uptake of extravasated albumin into the neurons. Protein synthesis assayed by in vivo [3H]leucine incorporation was reduced in regions showing calcium accumulation. Our observations suggest that neuroexcitation may play an important role in development of secondary and chronic changes after ischemic or traumatic brain insults. PMID- 2237988 TI - Intracellular free calcium increases in cultured cortical neurons deprived of oxygen and glucose. AB - Dissociated neocortical cultures from fetal mice exposed transiently to a medium lacking both glucose and oxygen developed neuronal degeneration without glial degeneration. We have found that this injury depends on extracellular calcium and is associated with uptake of calcium from the culture medium. We measured free cytoplasmic calcium in individual neurons using the fluorescent calcium indicator fluo-3 and provide evidence that oxygen and glucose deprivation injury increases the intracellular calcium signal. Both intracellular calcium elevation and subsequent neuronal loss could be blocked by the N-methyl-D-aspartate receptor antagonist dextrorphan. PMID- 2237989 TI - Reduced neurotoxicity in transgenic mice overexpressing human copper-zinc superoxide dismutase. AB - The role of oxygen-derived free radicals, superoxide in particular, in the pathogenesis of neuronal cell death induced by glutamate was studied using cultured cortical neurons from transgenic mice overexpressing human copper-zinc superoxide dismutase. Primary cortical neuron cultures were developed from 15-day old fetuses of both transgenic mice and their normal littermates. Both human copper-zinc-superoxide dismutase and host mouse copper-zinc-superoxide dismutase activities in cultured neurons were identified by native gel electrophoresis followed by nitroblue tetrazolium staining. Cultured neurons grown for 10-12 days in vitro were exposed briefly to 0.5 mM glutamate for 5 minutes, followed by biochemical and morphological examinations at 2, 4, and 24 hours. Our data have demonstrated that glutamate neurotoxicity is significantly reduced in transgenic neurons at 2 and 4 hours following exposure to glutamate, as measured by the efflux of lactate dehydrogenase, the 3-O-methyl glucose space, and by phase contrast and bright-field trypan blue staining. These data indicate that transgenic neurons containing twofold to threefold the normal amount of copper zinc-superoxide dismutase activity as the result of expression of the human copper-zinc-superoxide dismutase transgene are protected against glutamate neurotoxicity in vitro. Our results suggest that oxidative stress, at least in part, plays an important role in the biochemical pathways amplifying N-methyl-D aspartate receptor-mediated neurotoxicity. PMID- 2237990 TI - Nonsteroidal lazaroid U78517F in models of focal and global ischemia. AB - U78517F is a novel inhibitor of iron-catalyzed lipid peroxidation that combines the tetramethylchroman antioxidant ring portion of alpha-tocopherol with the amine of the previously described 21-aminosteroids (e.g., U74006F). U78517F inhibited 200 microM FeCl2-initiated lipid peroxidation in rat brain homogenates by 50% at a concentration of 0.6 microM compared with 8 microM for U74006F, 28 microM for alpha-tocopherol, and 43 microM for the ring portion of alpha tocopherol (i.e., trolox). U78517F is devoid of hypothermic or antiexcitotoxic actions or interactions with known neurotransmitter receptors. When administered intraperitoneally to male gerbils at 10 minutes before and again at the end of a 3-hour period of unilateral carotid artery occlusion, U78517F decreased 24-hour postischemic cortical neuronal necrosis. Neuronal density in the medial portion of the cortex was increased from 34.2% of normal in vehicle-treated animals to 86.3% in the U78517F-treated animals. In the lateral cortical area, the vehicle group showed only 3.3% neuronal survival versus 48.2% in the drug-treated group. In a separate series of experiments with the same focal ischemia model, identical dosing with U78517F enhanced the postischemic recovery of cortical extracellular calcium without any effect on ischemic or postischemic cortical blood flow. The effect on calcium recovery was observed at intraperitoneal doses as low as 0.1 mg/kg. The compound also was effective in partially attenuating 1-week postischemic hippocampal CA1 neuronal loss in a gerbil global ischemia model involving brief (15-minute) bilateral carotid occlusion, but sustained dosing was required. These results document the anti-ischemic efficacy of a novel and potent inhibitor of iron-catalyzed lipid peroxidation and further support a key role of oxygen radicals in postischemic brain damage. PMID- 2237991 TI - Platelet-activating factor. A putative mediator in central nervous system injury? AB - Platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3 phosphorylcholine) is a potent lipid autacoid produced by many cell types. Platelet-activating factor is produced by cerebellar granule cells in culture and has been extracted from brain tissue. Multiple platelet-activating factor receptors have been demonstrated in brain tissue. Activation of platelet activating factor receptors in transformed neuronal cell lines involved increases in intracellular calcium. Platelet-activating factor has potent actions on cerebral vessels and cerebral metabolism when administered in vivo, but may not have direct effects on brain microvessels. Excessive platelet-activating factor production in pathological states of the nervous system such as neurotrauma and stroke has been shown in only a few models (e.g., spinal cord ischemia and reperfusion or focal repercussion brain injury). In multiple studies using highly specific and potent platelet-activating factor antagonists, reversal or prevention of key consequences of brain injury such as hypoperfusion following ischemia, reperfusion and edema, inflammatory cell accumulation, neurologic/motor deficits, and neuronal salvage were demonstrated. This review provides and analyzes evidence in support of the role that platelet-activating factor might have in modulation of brain function and pathophysiological processes in brain ischemia and trauma. PMID- 2237992 TI - Hypoxic-ischemic damage and the neuroprotective effects of GM1 ganglioside. AB - In vitro studies have shown that monosialoganglioside GM1 reduces excitatory amino acid-related neurotoxicity by limiting the downstream consequences of abusive excitatory amino acid receptor stimulation. Systemic administration of GM1 appears to be efficacious in reducing acute neuronal damage and in facilitating medium- and long-term functional recovery after brain injury. We propose that GM1 protective effects in the acute injury phase results from attenuation of excitotoxicity, whereas the functional recovery seen at longer term could reflect GM1 potentiation of neuronotrophic factors. The potential therapeutic efficacy of GM1 administration in humans is suggested by clinical studies demonstrating improved neurologic outcome in stroke patients. PMID- 2237993 TI - The reliability of menses to indicate the return of ovulation in breastfeeding women in Manila, The Philippines. AB - Demographic studies generally use menses to indicate the return of fertility during breastfeeding. In a prospective study of 40 breastfeeding women in Manila, the resumption of ovarian activity was monitored by urinary hormone assays, and menstrual status was determined by weekly interview. For the women who menstruated before six months postpartum, first menses was not a good indicator of ovulation because there was a high proportion of anovular menses (67 percent), and the lag between anovular first menses and subsequent ovulation was 15.7 (+/- 4.4) weeks. After six months postpartum the proportion of anovular first menses declined to 22 percent, and the lag between anovular first menses and ovulation was 7.3 (+/- 4.6) weeks. If all anovular and ovulatory menstrual episodes are considered, the mean interval between first observed menses and first ovulation was 8.4 weeks during the first six months postpartum and only 0.1 week after six months. Thus, in breastfeeding women, menses is an inaccurate proxy measure for the timing of fertility return before six months postpartum, but a good indicator of the resumption of ovulation after six months. PMID- 2237995 TI - Mass media family planning promotion in three Nigerian cities. AB - Television promotion of family planning and clinic sites in three cities of Nigeria--Ilorin, Ibadan, and Enugu--played a significant role in 1985-88 in increasing the number of new acceptors at family planning clinics in each city. Family planning skits, prepared with advice and support from the local service providers, were included in existing popular entertainment shows. Questions asked in a recall survey among the exposed population in Enugu and Ibadan revealed that about half of those surveyed in both cities had seen the television episodes. Of those who had watched, 79 and 99 percent, respectively, recalled the family planning messages, and 69 and 88 percent, respectively, recalled specific clinic sites mentioned. Following the media promotion, the number of new clinic clients per quarter in Ilorin increased almost fivefold (in the original clinics evaluated); in Enugu, the number of new clients per month more than doubled; and in Ibadan, the number of new clients increased threefold. Use of entertainment through this "enter-educate approach" is a promising technique that can be replicated in different settings to encourage new clients to seek family planning services. PMID- 2237994 TI - An evaluation of Profamilia's female sterilization program in Colombia. AB - The findings of three surveys and three studies used by Profamilia to evaluate and improve their voluntary female sterilization program are presented. The surveys measured sociodemographic characteristics of users, factors behind the sterilization decision, and user satisfaction with the operation in the short run and over time. The studies explored methodologies for more accurate cost effectiveness analysis. Results of the projects were used by Profamilia management to identify areas of program strengths and weaknesses and to implement operational changes. PMID- 2237996 TI - Cultural influences on health care use: two regional groups in India. AB - While health care services are increasingly being seen as a major proximate determinant of decreased mortality in a population, it also seems to be the case that the mere provision of services does not lead to their better utilization. However, in general, it is difficult to explore differences in utilization because the availability of services itself varies so greatly. This report presents the results of a study in India of two distinct regional groups of similar socioeconomic status, residing in the same locality and, therefore, theoretically exposed to the same health services. Both groups share a strong faith in modern medicine (especially if it is obtained from a private practitioner) for the treatment of most common illnesses. However, important cultural differentials exist in the medical services sought for childbirth and in the treatment of morbidity in children of different ages and sexes. These cultural commonalities and differentials are described, their possible causes- primary among these being the status of women--explored, and some policy recommendations made. PMID- 2237997 TI - Islam and family planning acceptance in Bangladesh. AB - One frequently cited barrier to more widespread adoption of family planning in Moslem countries is religious opposition. To examine the depth and extent of such opposition in Bangladesh, 106 men who had been identified by their wives as religiously opposed to family planning were interviewed. Unexpectedly, 26 percent of the "opposing" husbands reported that they were current users of a contraceptive and an additional 50 percent, although not practicing, said they were in favor of family planning. Of the alleged "opposers," only 23 percent said they opposed family planning on religious grounds. One-fourth of this last group were able to cite specific islamic injunctions against family planning. It appears on the basis of these data, which were collected in the religiously conservative area of Lakshimipur, that the perception of widespread Islamic-based resistance to contraception in Bangladesh is not founded in fact. PMID- 2237998 TI - Botswana 1988: results from the demographic and health survey. PMID- 2238000 TI - Intracellular transfer of lipid molecules. PMID- 2237999 TI - Nonenzymatic proteins mediating intracellular lipid transport and metabolism. Current status and emerging trends. PMID- 2238001 TI - Glycolipid transfer protein in animal cells. PMID- 2238002 TI - Transport and metabolism of phosphatidylinositol in eukaryotic cells. PMID- 2238003 TI - Intracellular fatty-acid-binding proteins. Characteristics and function. PMID- 2238004 TI - Application of fluorescent phospholipid analogues to studies on phospholipid transfer proteins. PMID- 2238005 TI - Intracellular and extracellular flow of dolichol. PMID- 2238006 TI - Phospholipid transport in microorganisms. PMID- 2238007 TI - Intracellular trafficking of sterols. AB - Cavalier-Smith (1981) has identified 22 characters that are universally present in eukaryotes but absent in prokaryotes. Of these, he argues that one, exocytosis, might have been the driving force behind the evolution of modern eukaryotic cells. Bloom and Mouritsen (1988) further argue that sterols may have removed an evolutionary bottleneck to cytosis. Therefore, the advent of sterols in membranes might have been the single feature that led to eukaryote evolution. The evolutionary advantage conferred by cholesterol is associated primarily with plasma membrane function, since the majority of cellular free cholesterol resides in that membrane. However, sterol synthesis occurs in the ER; therefore, the cell must have a mechanism for transporting sterol to the plasma membrane and its regulation. As has been pointed out in this review, much remains to be elucidated in the study of intracellular sterol trafficking. To date, neither diffusion nor vesicle-mediated transport can be fully confirmed or ruled out. Microtubule and microfilament involvement appears important in some routes (e.g., mitochondria) but not in others. In addition, trafficking roles of cytoplasmic lipoproteinlike particles have not been addressed. Finally, although some "sterol carrier proteins" demonstrate the ability to mediate intervesicular transfer of cholesterol in vitro, the true physiological role of these proteins remains obscure. Future research in this field awaits the refinement of available techniques. Particularly valuable would be cytochemical methods for detection of sterol at the ultrastructural level. Possibly, direct microscopic visualization of radiolabeled components in cells represents the necessary approach. Purification of elements carrying newly synthesized sterols would allow the proteins mediating transport to be identified. Continued analysis of mutants defective in transport, such as in type C Niemann-Pick disease, will shed light on this complex problem. The importance of extracellular trafficking of cholesterol owing to its involvement in the progression of atherosclerosis, has been emphasized in recent years. Little emphasis has been placed on intracellular trafficking of sterol; however, it can be argued that such transport also plays a major role in atherosclerosis, possibly by fueling retrotransport of cholesterol to the liver and secretion in the bile. Therefore, we hope this review will serve to stimulate research interest in this area. PMID- 2238008 TI - Spontaneous transfer of lipids between membranes. PMID- 2238009 TI - Extra- and intracellular transport of retinoids. PMID- 2238010 TI - Phospholipid transfer proteins as probes of membrane structure and function. PMID- 2238011 TI - Intracellular transfer of phospholipids, galactolipids, and fatty acids in plant cells. PMID- 2238012 TI - The impact of a medical student's suicide. AB - The suicide of a medical classmate can have a profound effect upon the survivors. After the violent death of a third-year medical student at the University of California-San Francisco, the level of concern expressed in discussion groups suggested a need to study the impact in more detail. Interviews and scale data from 20 volunteer medical students identified a pattern of posttraumatic symptoms persisting over several months. The interviewees' tendency to identify with the victim was related to the prevalent experience of medical student depression. Specific suggestions are made both for immediate crisis management and for preventive intervention strategies within a medical school. PMID- 2238013 TI - Correlates of suicidal ideation among rural adolescents. AB - This study examined potential predictors of suicidal ideation among a nonclinical, rural adolescent population. A sample of 76 male and female adolescents enrolled in a rural public high school completed a personal information form, a suicide information questionnaire, short forms of the Beck Depression Inventory and the Family Environment Scale, and the Life Events Checklist. A stepwise multiple regression suggested significant predictive relationships between magnitude of suicidal ideation and measures of family social climate (i.e., Organization, Conflict, Expressiveness, and Independence subscales from the Family Environment Scale--Short Form). Multivariate analyses of variance and a discriminant-function analysis revealed no significant sex differences. PMID- 2238014 TI - Psychosocial vulnerability, life stress, and suicide ideation in a jail population: a cross-validation study. AB - The purpose of this present investigation was to cross-validate a stress psychosocial vulnerability model of suicidal ideation and behavior in a jail population. Measures of social alienation, cognitive distortions, adaptive resources, situational (jail environment) stress, depression, hopelessness, and suicide ideation were administered to 146 male inmates at a county jail facility. It was predicted that each of the vulnerability factors, in addition to jail stress, would be significantly related to suicide ideation among inmates. Furthermore, it was hypothesized that psychosocial vulnerability among inmates would interact with jail stress to best explain suicide intent. The result of a multiple-regression analysis, stepwise forward-inclusion algorithm, indicated that 51% of the variation in suicide ideation could be accounted for by the linear combination of low reasons for living, irrational beliefs, jail stress, and loneliness. In addition, when the variables were entered into a hierarchical multiple-regression model, interactions between select psychosocial vulnerability factors and jail stress were found to best explain suicide intent. Results of the study are discussed in terms of the proposed model, and implications for future research and prevention efforts in jail suicide are noted. PMID- 2238015 TI - Suicide in the Israeli army. AB - The present study was an attempt to analyze the problem of suicide in the Israel Defense Forces (IDF). Suicide is increasing among populations aged 18-21, which in Israel is the age when most young people are called up for a 3-year period of compulsory military service. The service may have a catalytic effect on suicide. but on the other hand may serve as a control mechanism reducing suicide. The study used data for the period 1974-1985, and examined suicide in combat and noncombat units by duration of service and by preservice psychiatric, medical, and motivational data. The suicide groups were also compared with a matched sample of nonsuicide groups along the relevant variables. The findings seem to be consistent with some established theoretical perspectives of situational stress, social support, and status incompatibility, and seem to bear practical implications for the reduction of suicide. PMID- 2238017 TI - Suicidal behavior and cognitive flexibility: design and verbal fluency after attempted suicide. AB - Aspects of problem solving were measured in nine male psychiatric patients, hospitalized after attempted suicide. Testing took place within 3 weeks (except for one patient) of the suicide attempt. Controls were patients with chronic idiopathic pain and healthy volunteers. Suicidal patients had significantly lower scores on general intellectual tests and in verbal and design fluency. No differences in problem solving (the Perceptual Maze Test and the Wisconsin Card Sorting Test) and flexibility (the Uses of Objects Test and the Stroop Test) were found. The results are interpreted as indicating a decreased ability of suicidal patients to generate new ideas, when no alternatives are provided. PMID- 2238016 TI - An application of the empirical Bayes approach to directly adjusted rates: a note on suicide mapping in California. AB - A simple, reliable, and comparable measure for suicide mapping and other health problems is needed. Because standardized mortality ratios (SMRs) may not indicate the relative meaning of their magnitudes when compared with one another, and statistical significance levels of tests for SMRs overlook the areas that have small populations, neither of these approaches provides a satisfactory index. The results using directly adjusted rates can be ordered directly according to their magnitudes. However, because of the lack of reliable estimates of local age specific rates, the usefulness of directly adjusted rates in mapping suicide is also limited. To extend the usefulness of directly adjusted rates, an empirical Bayes approach whereby information from other areas is borrowed to improve the precision of the estimates of local age-specific rates in calculating directly adjusted rates--especially in the areas with small population sizes--is proposed. When an empirical Bayes approach was applied to the 1983 suicide data for California counties, a more reasonable conclusion than could be obtained by using directly adjusted rates was reached. PMID- 2238019 TI - Surgical asepsis revisited. AB - Basic principles, rituals, and surgical conscience are essential components of surgical asepsis. Surgical asepsis has become too complicated. Protective asepsis describes principles of good hygiene, sanitation, and impeccable aseptic technique; the term has received renewed interest in the advent and increased awareness of bloodborne diseases. Rituals may actually enhance learning and efficiency in the operating room even though they may or may not directly affect nosocomial infection rates. PMID- 2238018 TI - Clinical issues: treating the difficult patient. PMID- 2238020 TI - What's happened to aseptic discipline in the OR? AB - Aseptic discipline is the sum of the constraining factors governing the human behavioristic interface between the surgical environment and the surgical patient. Although certain details of the discipline may change with advances in immunology, pharmacology, surgical techniques, instrumentation, and other elements in the surgical environment, the basic principles of aseptic discipline must prevail and be enforced. Surgical professionals enter into an unwritten covenant to keep an unspoken promise to discharge their unseen duties in the aseptic chain of events, with only their own consciences to monitor their responsibility to the patient. The discussion of aseptic discipline is divided into its application to the five D's of infection control: discipline, defense mechanisms, drugs, devices, and design of the environment. PMID- 2238021 TI - The nosocomial wound infection report. Its impact in the OR. AB - 1. Reporting surgical wound infection rates to the OR nurse is valued and used as a feed-back mechanism to monitor aseptic technique in the operating room. 2. At the institution surveyed, the chief influences on OR personnel's surgical aseptic practice were the OR nurse, followed by the infection control nurse and then the attending surgeon. 3. If the clean surgical wound infection rate was above 3%, the OR personnel would review preoperative and intraoperative risk factors at the institution surveyed. PMID- 2238022 TI - A review of antiseptics. Cleansing agents. AB - 1. The cells of the stratum corneum are rough, jagged, and contain myriad niches in which bacteria dwell. The complex structure of the stratum corneum limits complete access of any chemical; an antiseptic agent must have contact to kill bacteria. 2. Shaving hair on the skin, long considered essential prior to surgery, has been shown to sabotage the effectiveness of the preoperative skin preparation. 3. Experimental evidence over a long period has documented that no other agent can achieve as rapid and large a reduction in skin flora as alcohol. 4. The preoperative hand scrub calls not only for removal of dirt, grease, and pathogens from the surface of the hands, but also a maximum reduction of the resident flora. PMID- 2238023 TI - Disinfection in the OR. AB - 1. Items that enter sterile tissue or the vascular system are considered critical items and must be sterile (eg, surgical instruments, cardiac catheters, implants). 2. Semicritical items are those objects that come in contact with mucous membranes or with skin that is not intact. Endoscopes, anesthesia breathing circuits, respiratory therapy equipment, and endotracheal tubes are included in this category. These items require high-level disinfection. 3. Noncritical items (eg, floors, blood pressure cuffs) come in contact with intact skin. These items require low-level disinfection. 4. Flash sterilization is overused in hospitals. Control measures should be used to minimize infections traced to sterilizer failure. PMID- 2238024 TI - Environmental concerns in surgery in the 1990s. AB - 1. The surgical environment is the sum of the physical and the functional milieu in which surgical operative procedures are carried out in the course of patient care. 2. Although we acknowledge advances in surgical technology that have made possible a whole array of new procedures, we must be concerned with their effects on the surgical environment of the 1990s. These concerns include control of the spread of blood borne diseases and the lagging field of infectious and hazardous waste disposal. 3. The needs are clear for better departmental and institutional master planning, better systems analysis, better inservice training of personnel, and more precise and functional programming and planning. All must be accomplished within a framework of safety, efficiency, and economy. PMID- 2238025 TI - Keeping a lid on OR waste. PMID- 2238026 TI - It's second nature to me now. OR rituals. AB - Insufficient data exist relating to surgical asepsis; relying solely on data collection to determine practices limits patient care. Until clinical data are available that support or disclaim established traditions, it may be wise to hold customs that we believe have kept the patient safe. Rituals define and maintain sterility and provide freedom; certain traditions become part of the OR team's practice so that attention can be focused on the surgical procedure. As professional nurses, it is our responsibility to question dogma and to change our rituals when studies indicate the need for change. PMID- 2238027 TI - Syphilis screening in the 1990s. PMID- 2238028 TI - The prevalence of antibody to HTLV-I/II in United States plasma donors and in United States and French hemophiliacs. AB - Antibody to HTLV-I/II was detected in 19 (0.3%) of 6286 plasma donors from five regions of the United States (US). This seroprevalence rate is approximately 10 times that in whole blood donors. The regional distribution of infection was as follows: Southwest, 0.68 percent; Southeast, 0.45 percent; Midwest, 0.28 percent; Northwest, 0.1 percent; and Northeast, 0.0 percent. Rates of HTLV-I/II infection in blacks (0.74%) and Hispanics (0.66%) were higher (both, p less than 0.001) than those in whites (0.08%). All 19 infected units were donated by subjects aged 30 or older, even though 52.9 percent of the donations came from persons less than 30 years old. Equal rates of HTLV-I/II infection were found in men (0.31%) and women (0.29%). No HTLV-I/II antibody was detected in 154 French and 25 US hemophiliacs who were transfused regularly with noninactivated plasma or its derivatives. This suggests that the transfusion of HTLV-I/II-seropositive plasma products does not transmit the viral infection. PMID- 2238029 TI - American blood donors seropositive for human T-lymphotropic virus types I/II exhibit normal lymphocyte subsets. AB - Recent reports have demonstrated that some lymphocyte subsets are abnormal in Japanese blood donors who are seropositive for human T-lymphotropic virus type I (HTLV-I). To determine if similar changes characterize American blood donors who are seropositive for HTLV-I/II, lymphocyte subsets were measured in 42 HTLV seropositive and 42 HTLV-seronegative blood donors. The seronegative individuals were matched by age, race, and gender to the seropositive individuals. Peripheral blood mononuclear cells were treated with a panel of 12 monoclonal antibody pairs and then analyzed by two-color flow cytometry. No significant differences were observed between the seropositive and seronegative groups with respect to the absolute number of circulating lymphocytes or the percentages of lymphocytes belonging to the subsets assessed. These subsets included B, T, CD4, and CD8 cells and subpopulations of CD4 and CD8 cells defined by the coexpression of markers that appear (CD25, HLA-DR, CD38) or disappear (Leu 8, CD45RA) after activation. These findings indicate that HTLV-seropositive persons in the American blood donor pool do not exhibit the lymphocyte subset alterations reported for HTLV-I-seropositive blood donors in Japan. PMID- 2238030 TI - Evaluation of the manual hexadimethrine bromide (Polybrene) technique in the investigation of autoimmune hemolytic anemia. AB - The use of the direct manual hexadimethrine bromide (Polybrene) test (DPT) in the investigation of patients for autoimmune hemolytic anemia (AIHA) was evaluated. Seventy-nine blood samples from 68 patients were tested. A direct antiglobulin test (DAT) using monospecific reagents and the DPT were performed, and a concentrated ether eluate was tested. The DAT was positive in 62 (78%) of 79 patients and negative in 17 (22%). There is a good correlation among DAT, eluate, and DPT in demonstrating the presence of immunoglobulin on the red cell surface. In contrast, the DPT does not detect C3d and is often negative in cases of AIHA in which C3d alone is demonstrated by the DAT. In DAT-negative cases, DPT results correlated with reactive eluates. However, in four cases of steroid-responsive, DAT-negative hemolytic anemia, the DPT supported the diagnosis of AIHA when the eluate did not react. The DPT is a useful additional screening test for the investigation of AIHA, but it is not recommended as a replacement for either eluate testing or the DAT. PMID- 2238031 TI - An unexcluded paternity case investigated with hypervariable DNA loci. AB - A paternity case involving a putative father, a child, and the mother was referred to our laboratory for testing. Parentage was not excluded with 23 kinds of standard blood group markers and HLA, but the putative father requested more affirmative evidence of paternity. Seven kinds of DNA probes that recognize hypervariable loci were applied. On the basis of the allelic frequencies and their confidence intervals previously reported among unrelated Japanese individuals, as well as confirmed codominant segregation of the polymorphism, the exclusion probability and paternity index were calculated for this case. The cumulative paternity index from the seven DNA probes was 1.4 x 10(6), which was 316 times higher than that from the 23 standard blood group markers and HLA. Accordingly, DNA polymorphism is considered to be informative enough for paternity testing. PMID- 2238032 TI - Density gradient separation of peripheral blood stem cells: comparison of an automated cell processing device and manual methods. AB - Peripheral blood stem cells were collected from normal donors by leukapheresis on a cell separator. The leukapheresis product contained 1.5 x 10(10) mononuclear cells (MNCs) and was divided into two aliquots that underwent either automated or manual density gradient separation with ficoll-hypaque and subsequent washing. In the automated process, recovery of MNCs was 85 percent, reduction in platelet content was 64 percent, and the final hematocrit (Hct) was less than 1 percent. The manual separation resulted in 76-percent MNC recovery, a 79-percent reduction in platelet content, and a final Hct of less than 1 percent. The purified MNCs were then placed in methylcellulose culture at a concentration of 4 x 10(5) MNCs per mL. Quadruplicate 1-mL aliquots were cultured, and colonies were counted and classified on Day 14. Comparison of automated and manual ficoll-hypaque separations demonstrated no differences in the total, erythroid, or granulocyte macrophage colony numbers. The cell processor used is fast, reliable, uncomplicated, and provides a sterile product containing progenitor cells that are not adversely affected by the automated ficoll-hypaque separation. PMID- 2238033 TI - Efficiency of white cell filtration and a freeze-thaw procedure for removal of HIV-infected cells from blood. AB - Strategies for diminishing the risk of blood transfusion-associated transmission of HIV-1 were evaluated. HIV-1-infected peripheral blood mononuclear cells were added to blood that was subsequently filtered by using different white cell (WBC) filters (cellulose acetate and polyester). The average log reduction of infected cells with polyester filters was at least 2.5 as measured by ID50 titration and polymerase chain reaction. In two WBC filtration experiments with blood from seropositive donors diluted 1:4 with seronegative blood, log reductions of 2.4 and greater than 2.5 were observed. No cell-free virus was retained by the filter used. A freeze-thaw procedure applied to HIV-1-contaminated blood resulted in a minimal log reduction. These results indicate that the reduction of HIV-1 infectivity as a result of filtration is mainly due to the removal of HIV-1 infected WBCs, and that complete removal of infected WBCs cannot be achieved by the current filtration or freeze-thaw procedures. However, the development of filters with enhanced ability to remove (possibly infected) WBCs may have the added benefit of improving the safety of donor blood, especially in multiply transfused patients. PMID- 2238034 TI - Life-threatening, antiglobulin test-negative, acute autoimmune hemolytic anemia due to a non-complement-activating IgG1 kappa cold antibody with Pra specificity. AB - A 21-year-old man with fulminant cold autoantibody hemolytic anemia (CAHA) was hospitalized with hemoglobinemia, hemoglobinuria, hemoglobin concentration of 3.3 gm per dL, a negative direct antiglobulin test (DAT) with polyspecific and anti C3d reagents, a negative Donath-Landsteiner test, and a cold agglutinin titer of 80. He failed to respond to corticosteroids, multiple plasma exchanges, and cyclophosphamide; he required 54 transfusions in 10 days to maintain a hemoglobin concentration of 6.0 to 10.0 g per dL. He improved dramatically after a splenectomy was performed. The wide-thermal-amplitude cold agglutinin proved to be an IgG1 kappa antibody with Pra specificity. The patient's serum exhibited normal complement activation. When the DAT was carried out at 0 to 4 degrees C, the result was strongly positive for IgG; the indirect antiglobulin test at 0 to 4 degrees C was positive with the patient's serum diluted 1 in 640. Within 6 months, he was in complete remission and receiving no therapy. As compared with eight patients with CAHA that was exclusively IgG-mediated, this patient is remarkable for his requirement for many transfusions and for DATs that were consistently negative for C3d. PMID- 2238035 TI - Syphilis and blood transfusion: a global perspective. PMID- 2238036 TI - HLA-matched blood products and posttransfusion graft-versus-host disease. PMID- 2238037 TI - The pH value in platelet concentrates prepared and stored for 5 days in bags of seven manufacturers. PMID- 2238038 TI - Transmission of HIV-1 by component type and duration of shelf storage before transfusion. PMID- 2238039 TI - A 'swell' way to regulate metabolism. PMID- 2238040 TI - The major blood group ABO(H) determining genes are isolated. PMID- 2238041 TI - Halophilic proteins and the influence of solvent on protein stabilization. AB - Competition between protein-solvent and protein-protein interactions is arguably the most important contributing factor to polypeptide folding in general. A study of halophilic proteins, correlating their stability and solution structures in different conditions, focuses on the effects of a high salt solvent. A mechanism is proposed to explain how these proteins have adapted to such an extreme environment. PMID- 2238042 TI - Non-cholinergic actions of acetylcholinesterases: a genuine peptidase function or contaminating proteases? PMID- 2238043 TI - Endocrinization of the early embryo: an emerging role for hormones and hormone like factors. AB - In the last decade, we witnessed the extension of endocrinologically based concepts and molecules to many other arenas of intercellular communication, e.g. immunology, hematology and cancer biology. At the start of the new decade we are witnessing the beginning of a similar transformation in our understanding of early embryogenesis, i.e. that hormones, growth factors and other hormone-like agents and their receptors, familiar to us in other contexts, may be the long sought mediators of many key events in early embryogenesis. Why these agents were overlooked before and how they have started to emerge is the theme of this essay. The title 'Endocrinization of the Early Embryo' refers to both the biological and intellectual developments. PMID- 2238044 TI - Protein kinase recognition sequence motifs. AB - Protein kinases play a crucial role in the regulation of many cellular processes. They alter the functions of their target proteins by phosphorylating specific serine, threonine and tyrosine residues. Identification of phosphorylation site sequences and studies with corresponding model peptides have provided clues to how these important enzymes recognize their substrate proteins. This knowledge has made it possible to identify potential sites of phosphorylation in newly sequenced proteins as well as to construct specific model substrates and inhibitors. PMID- 2238046 TI - Protein transport across the ER membrane. AB - Protein transport across the endoplasmic reticulum (ER) membrane may be divided into two phases: an initiation or targeting cycle, which has been fairly well characterized, and the actual transfer of the polypeptide chain through the membrane, the mechanism of which is still unknown. In this review, the initiation cycle is discussed with emphasis on the mechanism of signal sequence recognition by the 54 kDa polypeptide of the signal recognition particle (SRP) and on the efficiency of targeting of nascent chains. Recent results are reviewed suggesting the transfer of the polypeptide chain by means of a translocation complex, a constituent of which appears to be the signal sequence receptor protein (SSR). PMID- 2238045 TI - Self-splicing group II and nuclear pre-mRNA introns: how similar are they? AB - The splicing pathway of pre-mRNA introns bears similarities to that of the group II introns, some members of which undergo self-splicing. The snRNAs may provide the pre-mRNA introns with RNA structures in trans comparable to those available in cis in group II introns. This article examines the available evidence for the hypothesis that the catalysis of these two splicing pathways is fundamentally equivalent. PMID- 2238047 TI - Regulation of MHC transcription. PMID- 2238048 TI - Time-related morphological changes in cold-stored rat livers. A comparison of Euro-Collins solution with UW solution. AB - Rat livers were stored in cold UW solution and Euro-Collins solution for various periods. Morphological investigations were performed using light microscopy, as well as scanning and transmission electron microscopy. In the UW-stored livers, the appearance of blebs derived from hepatocytes and the destruction of sinusoidal endothelial cells (SEC) occurred more slowly than in the EC-stored livers. Almost no ultrastructural damage in the hepatocytes was observed even after 48 hr of storage in UW solution, while extremely swollen and degenerated hepatocytes were observed in the 48-hr EC-stored livers. After 48-hr of storage, livers stored in UW solution lost 7.9% of their weight though EC-stored livers gained 29.7% of weight. Light microscopic morphometry revealed that there was a significant increase of 24.3% in the mean hepatocyte area of 24-hr EC-stored livers, whereas the UW-stored hepatocytes did not show any significant increase even after 48 hr of storage. After perfusion fixation, livers stored for more than 8 hr in EC solution showed a mosaic pattern of uneven fixation indicating a microcirculatory disturbance, whereas the UW-stored livers showed a rather uniform fixation after 12 hr of storage. It is suggested that the microcirculatory disturbance occurred more slowly in the UW-stored livers than in the EC-stored livers, which might be due to the protection of SEC and the suppression of bleb formation and the swelling of hepatocytes by UW solution. PMID- 2238049 TI - Evidence of mitochondrial impairment during cardiac allograft rejection. AB - NADH laser fluorimetry and mitochondrial oxigraphy were used to study myocardial oxidative energy metabolism during cardiac allograft rejection. Heterotopic cardiac transplantation was performed on Lewis rats; allografts (with Fischer rat donors) were compared with isografts (with Lewis rat donors). In vivo and in vitro assays were performed six days after transplantation. Myocardial NADH fluorescence was recorded in vivo from grafted hearts, at baseline; during brief, complete ischemia; and during reperfusion. Oxygen consumption of mitochondria isolated from both native and grafted hearts was determined. Neither baseline levels nor maximum ischemic levels of NADH fluorescence (F0 = k[NADH]) were found to be significantly different between allografts (0.45 +/- 0.05 to 0.87 +/- 0.10) and isografts (0.45 +/- 0.04 to 1.11 +/- 0.05). During recovery, the rate of fluorescence decrease was significantly lower in allografts than in isografts (0.024 +/- 0.001 vs. 0.038 +/- 0.002 delta F0.s-1, P less than 10(-3], indicating a lower rate of NADH reoxidation. In the presence of malate and glutamate substrates, mitochondrial O2 consumption was significantly lower in allografts than in isografts (30 +/- 9 vs. 100 +/- 15 nanoatoms O2. min-1.mg prot-1, P less than 10(-2]. These results indicate that mitochondrial oxidative metabolism was impaired during the rejection process. Such energy production disturbances may contribute to the dysfunction of rejecting hearts. PMID- 2238050 TI - Ranolazine--a new drug with beneficial effects on renal preservation. AB - Ranolazine is a new drug with a novel mode of action as a metabolic modulator and membrane stabilizer. In this prospective randomized double-blind trial, a porcine model of renal autotransplantation was used to assess the effects of this drug during preservation and reperfusion of kidneys cold-stored for 24 hr in phosphate buffered sucrose (PBS140). Three groups of 10 animals were compared: a Placebo group (placebo given intravenously to the animal before nephrectomy, added to the preservation solution, and given again to the animal during reperfusion); a Storage group (Ranolazine before and during storage, placebo during reperfusion); and a Reperfusion group (placebo before and during storage, Ranolazine during reperfusion). Detailed analysis of posttransplant renal function was carried out over a 14-day follow-up period. There were 7 deaths with primary nonfunction: 2 Placebo, 1 Storage, 4 Reperfusion. Analysis of the whole group and separate analysis of the survivors demonstrated significantly improved glomerular (P less than 0.05), tubular (P less than 0.05), and loop of Henle (P less than 0.05) function in the Storage group. The results of this study clearly demonstrate the beneficial effects of Ranolazine during the storage phase of porcine renal preservation, and further investigation of this drug is warranted. PMID- 2238052 TI - Development of stable mixed T cell chimerism and transplantation tolerance without immune modulation in recipients of vascularized bone marrow allografts. AB - A consistent majority (62.5%) of immunologically unmodified rat recipients transplanted with vascularized hind-limb bone marrow allografts across a semiallogeneic transplant barrier developed tolerance with absence of graft versus-host disease. A minority of recipients (37.5%) demonstrated lethal GVHD. Transplantation tolerance in the majority was associated with the induction of stable low-level mixed T cell chimerism, including donor CD5+, CD4+, and CD8+ lymphocytes. Chimeras were specifically immune nonresponsive to host alloantigenic determinants. These results emphasized a potentially important mechanism for low-level stable mixed lymphoid chimerism (SMLC) in tolerance induction, independent of immune suppressive effects due to irradiation or immunopharmacologic intervention. These vascularized bone marrow transplantation (VBMT) results may establish the experimental foundation for a novel approach to stem cell transfer and bone marrow transplantation. PMID- 2238051 TI - Use of yttrium-90-labeled anti-Tac antibody in primate xenograft transplantation. AB - The high-affinity interleukin-2 receptor (IL-2R) is expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting cells. Thus, blockade of the interaction of IL-2 with its receptor could achieve selective immunosuppression. Accordingly, anti-Tac, a murine IgG2a class monoclonal antibody specific to the IL-2R, was used alone or in a chelated form with yttrium-90 (90Y), a pure beta emitter, to inhibit rejection of cardiac xenografts from Macaca fascicularis (cynomolgus) donors transplanted to the cervical or abdominal region of Macaca mulatta (rhesus) recipients (n = 20). Animals received no immunosuppression (n = 3, group I, controls), unmodified anti Tac (n = 5, 2 mg/kg q.o.d., group II), or 90Y-anti-Tac (n = 5, 16 mCi, group III). To distinguish the nonspecific immunosuppressive effect of radiation, 90Y was administered bound to UPC-10 (n = 4, 16 mCi, group IV), another murine monoclonal antibody that does not specifically recognize activated immunoresponsive cells. All immunosuppression was administered in divided doses during the first 2 weeks posttransplant. Group I animals rejected their grafts at 6.7 +/- 1 days and demonstrated a rise in soluble IL-2R levels at the time of rejection, indicating the generation of Tac-expressing and -releasing cells. Graft survival in group II was not prolonged compared with controls (mean survival 6.2 +/- 1 days; P greater than 0.05). In contrast, graft survival in animals that received the designed dosage of 90Y-anti-Tac was significantly prolonged to an average of 38.4 +/- 5 days compared with groups I and II (P less than 0.005 and P les sthan 0.0005, respectively). Prolongation of graft survival occurred in animals that received 90Y-UPC-10 (mean survival 21.3 +/- 5 days, P less than 0.05 versus group I, P less than 0.01 versus group II). However, 90Y UPC-10 was significantly less effective in prolonging graft survival than 90Y anti-Tac, in which one-half the per-kilogram dosage of radioactivity was delivered in specific fashion via anti-Tac (P less than 0.025). Reversible nonlethal bone marrow suppression occurred without associated nephro- or hepatotoxicity, and virtually all animals developed antibodies to the murine monoclonal. Thus, the approach used in the present study, IL-2R-directed therapy with 90Y-anti-Tac, may have potential applications in organ transplantation and in the treatment of Tac-expressing neoplastic diseases. PMID- 2238053 TI - Methotrexate as an adjunct in the treatment of persistent mild cardiac allograft rejection. AB - Because methotrexate arrests inflammation in autoimmune disease, we studied its efficacy in persistent low-grade cardiac allograft rejection. Seventeen patients aged 39.5 +/- 0.9 years (mean +/- SE) had persistent rejection despite previous therapy with high dose corticosteroids. Maintenance immunosuppression consisted of prednisone, azathioprine, and cyclosporine. The rejection episode treated with methotrexate occurred 180 +/- 55.4 days posttransplantation. Patients had incurred 2.7 +/- 0.3 previous episodes of rejection with the first episode occurring 30.6 +/- 6.2 days post transplant. Methotrexate was administered orally in 3 doses to an average weekly dose of 12.8 +/- 0.8 mg. The duration of methotrexate therapy was 9.0 +/- 1.1 weeks. Sixteen of the seventeen persistent rejection episodes resolved by 22.8 +/- 3.2 days of methotrexate therapy. Using methotrexate, the prednisone dose was decreased from 22.4 +/- 4.8 mg/day at initiation of methotrexate to 9.7 +/- 1.4 mg/day at the completion of methotrexate therapy (P less than 0.01). Over a 306 +/- 35-day follow-up, 9 of 17 patients (53%) have remained rejection-free. Leukopenia, necessitating reduction in azathioprine occurred in 10 patients. One patient developed herpes zoster during therapy. These data indicate that methotrexate is effective in resolving persistent cardiac allograft rejection with minimal morbidity. In addition, the use of methotrexate for treatment of rejection allows reduction in maintenance corticosteroid doses. PMID- 2238054 TI - Percutaneous needle biopsy of the renal allograft. A clinical safety evaluation of 1129 biopsies. AB - In many transplant centers there is a reluctance to perform percutaneous core needle biopsies in renal allografts for fear of complications that may jeopardize the graft. We have evaluated the safety of percutaneous renal allograft biopsy by retrospectively studying 1129 biopsy specimens in 513 patients between 1974 and 1988. All biopsies were performed with a conventional 2.0 mm TruCut disposable needle (Travenol Labs.; Deerfield, IL) without radiographic aid for localization of the kidney. Kidney tissue was obtained in 1095 cases (97.0%). In 1037 biopsies (91.9%) enough renal tissue for histological evaluation was obtained. In 34 biopsies (3.0%) no renal tissue and in 58 (5.1%) only renal medulla was found. All the complications were demonstrated by with macroscopic bleeding into the urinary tract system. Thirty-two patients (2.8%) developed hematuria requiring hospitalization and some type of active treatment (catheter-a-demeure, n = 14; cystoscopy, n = 11; percutaneous nephrostomy, n = 3; surgery, n = 4). On 8 biopsy occasions blood transfusion was required. Three graft removals (0.3%) were attributed to the procedure of biopsy for emergency diagnostic purposes. All three grafts were severely damaged by rejection and had little or no function. No grafts were lost among the biopsies taken for long-term follow-up. No deaths occurred. Biopsies yielding only renal medulla were found to carry a greater risk of bleeding than adequate biopsy specimens (P less than 0.001), as did biopsies from transplants with acute vascular rejection. Conversely, biopsies taken for routine check-ups of long-term renal allografts were associated with a lower risk than biopsies taken because of poor or deteriorating renal function (P less than 0.05). An analysis of 340 biopsies, taken in accordance with a protocol during periods of stable renal function, revealed no deterioration in graft function at 1 and 12 months after the biopsy. In this study, we have found that conventional percutaneous needle biopsy of the renal allograft involves a certain risk of complications, even including graft loss. We have also defined a number of risk factors for such complications. However, we think that the benefits outweigh the risks, and needle biopsy should therefore remain an important diagnostic tool among all the others in the posttransplantation management of the renal transplant recipient. PMID- 2238055 TI - Orthotopic liver transplantation for Byler disease. AB - Byler disease is a rare form of familial intrahepatic cholestasis that is fatal before puberty. This retrospective study reviewed the results of orthotopic liver transplantation in 14 children with Byler disease using 12 whole-liver grafts and 2 reduced-size grafts. One post-operative death occurred after retransplantation for arterial thrombosis. In the other patients, infectious problems and rejection episodes were the most frequent complications during the postoperative period. In the 13 patients alive, graft function, growth, and quality of life were good after an average follow-up of 17 months without any sign of disease recurrence. PMID- 2238056 TI - 8-Methoxypsoralen and ultraviolet A therapy for cutaneous manifestations of graft versus-host disease. AB - The potentially beneficial effect of 8-methoxypsoralen and ultraviolet A (PUVA) irradiation for treatment of drug-resistant cutaneous manifestations of graft versus-host disease led us to investigate the effect of this therapy in a larger series of patients with GvHD. To date, 11 patients with histologically demonstrated cutaneous GvHD (acute GvHD grade III-IV in 4 patients, extensive lichenoid chronic GvHD in 6 patients, sclerodermatous chronic GvHD in 1 patient) have received PUVA treatment for 2-24 weeks. All patients have been on CsA for GvH prophylaxis; 5 with mismatched grafts had additionally received methotrexate or monoclonal antibody campath-1 after bone marrow transplantation. Seven patients were on CsA and prednisolone; 2 patients on CsA, prednisolone, and azathioprine; 1 patient on azathioprine and prednisolone; and 1 patient had no immunosuppressive treatment for the duration of PUVA treatment. The 8 methoxypsoralen (0.6 mg/kg bw) was given as photosensitizer before each ultraviolet A irradiation (0.3-8.5 joules/cm2). The only observed adverse reaction was mild nausea. In all patients improvement of cutaneous lesions could be observed with complete response in 5 patients and partial response in 6 patients. Immunosuppressive drugs could be withdrawn in 2 patients and reduced in 8 patients after initiation of PUVA treatment. These findings suggest that PUVA therapy may be a useful adjunct to conventional therapy for cutaneous GvHD. PMID- 2238057 TI - MHC class II reactivity of human villous trophoblast in chronic inflammation of unestablished etiology. AB - Absence of class II MHC antigens from human syncytiotrophoblast is a common finding in normal-term placentae. Since chronic villitis of unestablished etiology is a placental lesion frequently found in normal and abnormal term placentae, and fetal stem vessels are MHC class II-positive in these lesions, we asked if syncytiotrophoblast in villitis is reactive for MHC class II antigens. We found segments of syncytiotrophoblast that were reactive for the MHC class II HLA-DR, DP, and DQ antigens in villitis areas of normal-term placentae and in placentae from women with a history of recurrent spontaneous abortions. This reactivity was not due to trophoblast replacement by activated macrophages, though the possibility of crossreactive antigens and binding of soluble MHC class II antigens by receptors developed in areas of villitis could not be excluded. MHC class II antigen expression on syncytiotrophoblast could be due to cytokine release from activated macrophages and helper T lymphocytes which we have previously described in areas of villitis of unestablished etiology. PMID- 2238058 TI - Morphological changes in rat pancreatic acinar cells induced by long-term treatment with cyclosporine and their reversal after withdrawal. AB - Cyclosporine (CsA), administered to rats at daily doses of 10 and 50 mg/kg body weight, for 21 days, influenced negatively the structures involved in the synthesis, storage and secretion of digestive enzymes in pancreatic acinar cells. A dose-related, significant reduction in basophilic cell regions, secretion granule content, and overall size of acinar cells was appreciable by light microscopy and morphometry. By electron microscopy, the acinar cells of the rats given 10 mg/kg/day CsA were similar to the controls, whereas with the higher dose most cells showed reduction in the size of nucleoli, increase in the number of lysosomes, and evidence of autophagy. In only a few cells was autophagy particularly severe and involved almost the entire cytoplasm. Nine weeks after withdrawal from CsA treatment, the structural recovery of acinal cells was complete, and features indicating enhanced protein synthesis and mitochondrial multiplication were observed by electron microscopy. In conclusion, prolonged administration of CsA to rats induces changes in the acinar cells indicating a depression of their activity, without substantial impairment in the viability of the most of them, even at high doses. This accounts for complete restoration of the acinar tissue upon withdrawal. PMID- 2238059 TI - Mechanisms of total lymphoid irradiation-induced immunosuppression. II. Failure of con A-stimulated splenocytes from TLI-treated mice to express IL-2 and IL-2 receptor RNA. AB - Total lymphoid irradiation is a radiotherapy procedure used as an alternative immunosuppressive regimen in organ transplantation. Following TLI mature lymphocytes are depleted, and splenocytes do not proliferate to mitogens, produce IL-2, or express IL-2 receptors. We now show that mitogen stimulated splenocytes from TLI-treated mice do not secrete IL-2 protein by an IL-2 ELISA assay. Northern blot analysis and RNase protection assays reveal that TLI splenocytes do not make IL-2 RNA or IL-2 receptor RNA following mitogen stimulation. TLI splenocytes produce at least 1000 times less IL-2 RNA after Con A stimulation than normal splenocytes. TLI therapy resembles anti-CD4 therapy and CsA in that each results in an IL-2-"depleted" state. PMID- 2238060 TI - Inhibition of leukocyte chemotaxis by immunosuppressive agents. Specific inhibition of lymphocyte chemotaxis by cyclosporine. AB - Since chemotaxis is an important mechanism by which leukocytes are recruited to allografts during rejection, the effect of immunosuppressant agents on in vitro chemotactic responses of neutrophils, monocytes, and lymphocytes was studied. Cyclosporine caused profound inhibition of lymphocyte chemotaxis to three different chemotactic factors at pharmacologic levels but had no effect on neutrophil or monocyte chemotaxis. Methylprednisolone and azathioprine both inhibited chemotactic responses of neutrophils and monocytes as well as lymphocytes. These data suggest that immunosuppressant agents are potent inhibitors of leukocyte chemotaxis and that drugs differ as to which leukocyte cell type they inhibit. The selective action of cyclosporine might explain why this drug is ineffective in reversing established rejection episodes in which monocytes and neutrophils are also involved. Inhibition of leukocyte chemotaxis may be an important mode of action of immunosuppressant drugs, and drug regimes might be adjusted to cause selective inhibition of particular cell types. PMID- 2238061 TI - Induction of HLA-specific CTL to nonimmunogenic, heat-inactivated lymphocytes by interleukin 2. AB - Human lymphocytes that have been heat-inactivated (1 hr, 45 degrees C) were used as stimulator cells in a model system to study the requirements of allogeneic T cell activation in vitro. Cytotoxic T lymphocytes were not generated in either primary or secondary mixed lymphocyte cultures after exposure to heated stimulator cells. Successful reconstitution of cytolytic activity in primary cultures was achieved by the addition of rIL-2. Further, cytotoxic T cell lines could be maintained in culture for several weeks by stimulation with heated allogeneic cells and periodic addition of exogenous IL-2. The cytotoxic T cells generated in primary cultures or in the T cell lines were specific for the HLA class I antigens of the stimulating cells. Thus, the combination of heated cells and IL-2 stimulated antigen-specific cytotoxic cells, and not merely lymphokine activated killers. Although IL-2 production appeared to be a crucial missing component of MLCs with heated lymphocytes, the addition of IL-1, a factor known to act as a second signal for stimulating IL-2 production, did not reconstitute cytolytic activity. These results indicate that (1) heat treatment does not appreciably affect class I structure; (2) HLA class I/T cell receptor interactions are intact, resulting in responsiveness to IL-2 but not IL-1; and (3) heating creates a defect that has a minimal effect on CTL precursor activation but does disrupt a T helper cell/stimulator cell interaction critical for IL-2 production. PMID- 2238062 TI - A cadaveric kidney transplant functioning for a quarter of a century--a case report. PMID- 2238063 TI - Development of a malignant tumor in a liver transplant graft procured from a donor with a cerebral neoplasm. PMID- 2238064 TI - The impact of ischemic and immunologic factors on early graft function in pediatric renal transplantation. PMID- 2238065 TI - Reduced bone mineral density in men and women with allogeneic bone marrow transplantation. PMID- 2238066 TI - Adult respiratory distress syndrome following chronic rejection of a pancreatic allograft--a case report. PMID- 2238067 TI - The therapeutic role of plasma exchange in acute renal allograft rejection. PMID- 2238068 TI - Combined liver-kidney transplantation in primary hyperoxaluria type 1. PMID- 2238069 TI - Effect of ciprofloxacin on cyclosporine pharmacokinetics. PMID- 2238070 TI - Pharmacokinetics of cyclosporine in the weanling pig. PMID- 2238071 TI - Lack of effect of portal diversion on the outcome of liver allograft in rats. PMID- 2238072 TI - Prolongation of survival of discordant kidney xenografts by C6 deficiency. PMID- 2238073 TI - Immunocytochemical investigations of vessel allograft arteriosclerosis using smooth muscle cell- and macrophage-specific monoclonal antibodies. PMID- 2238074 TI - Changes in proximal tubular morphology following hypothermic storage in two preservation solutions. A comparative study using canine and porcine kidneys. PMID- 2238075 TI - University of Wisconsin solution without lactobionate and raffinose. Protection of metabolism in cold-stored kidneys. PMID- 2238076 TI - The influence of matching in living-related transplants. PMID- 2238077 TI - Rapid assessment of S. cerevisiae mating type by PCR. PMID- 2238078 TI - The trouble with 'PCR' machines. PMID- 2238079 TI - In situ hybridization to pre-fixed polytene chromosomes. PMID- 2238080 TI - The continuing search for the mammalian sex-determining gene. PMID- 2238082 TI - Determination of 3' end processing in retroelements. PMID- 2238081 TI - Ribonucleotide reductase and its regulation during the cell cycle. PMID- 2238083 TI - PCR amplification of plasmid inserts from bacterial colonies and their restriction analysis in a single tube. PMID- 2238084 TI - Quick DNA recovery from agarose gels by ultracentrifuge run. PMID- 2238085 TI - Genetic mapping of common diseases: the challenges of manic-depressive illness and schizophrenia. AB - Advances in genetic mapping of human diseases have led to the identification of single locus susceptibility for several common disorders. There have been a number of reports of linkage for the psychiatric disorders manic-depressive illness and schizophrenia, but none of these linkage reports is uncontested. Nonetheless, it appears promising to continue attempts to map these psychiatric disorders, since linkage can now be detected even when the inheritance is complex and includes genetic heterogeneity and variable penetrance. PMID- 2238086 TI - Making stripes in the Drosophila embryo. AB - The striped pattern of expression of the Drosophila primary pair rule genes is controlled by independent regulatory units that give rise to individual stripes. The different stripes seem to respond in a concentration-dependent manner to the different combinations of maternal and gap protein gradients found along the anterior-posterior axis of the early embryo. Thus, the initial periodicity appears to be generated by putting together a series of nonperiodic events. PMID- 2238087 TI - Brittle bones--fragile molecules: disorders of collagen gene structure and expression. AB - Mutations in the genes that encode the chains of type I collagen, the major structural protein in most tissues, usually produce brittle bones. The consequences of even apparently minor mutations--single base substitutions--can range from lethal to mild, and the phenotypic consequences reflect the nature and position of the mutation. The manner in which phenotypes are produced depends on the effect of the mutation on the structural integrity of the molecule and on whether or how the abnormal molecules can be incorporated into an extracellular matrix. PMID- 2238088 TI - Transcriptional enhancers can act in trans. AB - Enhancers have been defined operationally as cis-regulatory sequences that can stimulate transcription of RNA polymerase-II-transcribed genes over large distances and even when located downstream of the gene. Recently, it has become evident that enhancers can also stimulate transcription in trans if they are brought into close proximity to the promoter/gene. These reports provide clues to the mechanism of remote enhancer action. In addition, the findings, together with genetic studies in Drosophila, strongly suggest that enhancer action in trans could underlie phenomena such as 'transvection', where one chromosome affects gene expression in the paired homolog. PMID- 2238089 TI - Overcoming barriers to the oral administration of peptide drugs. PMID- 2238090 TI - Caffeine as a model drug of abuse. PMID- 2238091 TI - Subtypes of the D2 dopamine receptor. PMID- 2238092 TI - Pharmacology of alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase. AB - alpha-Fluoromethyl-[S]-histidine (FMH) is a specific and potent inhibitor of histidine decarboxylase, which forms histamine from histidine. It acts selectively and irreversibly by formation of a covalent linkage, possibly with the serine residue in the active site of the enzyme. A single administration of FMH decreases the histamine content only of non-mast cells in the brain and stomach of rodents, but repeated administration gradually decreases the histamine content of mast cells in all tissues. Thus, FMH can be used to deplete histamine in pharmacological studies. As no marked side-effects have been observed during administration of FMH, it may be useful in pathological conditions, such as some allergic diseases, peptic ulcers and mastocytosis, in which excess production of histamine is involved. PMID- 2238093 TI - Immunomodulatory activity of small peptides. AB - The activity of the immune system can be modulated by a wide variety of natural and synthetic peptides. Here, Vassil St Georgiev summarizes the actions of some of the immunostimulatory and immunosuppressant small peptides that have shown most promise as therapeutic agents. Some are already in use as vaccine adjuvants or to prevent graft rejection. There are now indications that these peptides may also be of benefit in conditions in which the immune system is compromised, in autoimmune disease and in cancer. PMID- 2238094 TI - Excitatory amino acid neurotoxicity and neurodegenerative disease. AB - The progress over the last 30 years in defining the role of excitatory amino acids in normal physiological function and in the abnormal neuronal activity of epilepsy has been reviewed in earlier articles in this series. In the last five years it has become clear that excitatory amino acids also play a role in a wide range of neurodegenerative processes. The evidence is clearest where the degenerative process is acute, but is more controversial for slow degenerative processes. In this article Brian Meldrum and John Garthwaite review in vivo and in vitro studies of the cytotoxicity of amino acids and summarize the contribution of such toxicity to acute and chronic neurodegenerative disorders. PMID- 2238095 TI - [Fetal chromosome studies in the first trimester of pregnancy]. AB - The possibility of transcervical biopsy of chorion by the method of forceps and production of "direct" preparations of chromosomes in the first trimester of pregnancy has been studied. Satisfactory preparations are obtained during short term incubation of villi for 24 and 48 hours. Portion of complete metaphases constitutes 0.23. PMID- 2238096 TI - [The incorporation of macromolecules into the germ cells of male mice via electroporation and dimethyl sulfoxide]. AB - Electroporation (incorporation of macromolecules into the living cells by means of electric pulses) provides inclusion of plasmid 14C-DNA into immature cells of spermatogenic epithelium. The highest level of foreign DNA incorporation into spermatocytes and spermatids has been induced by 8kV electric pulses applied 3 times with 20 sec intervals. Meanwhile, mature sperms are found to be exclusively resistant to exogenous DNA irrespective of the voltage level, the number of pulses and Ca++ uptake (contents). Incubation of mature sperms for two hours in the medium with Ca++ (10 mM) and dimethylsulfoxide--(DMSO, 33%) provides highly reliable incorporation of plasmid 14C-DNA into sperm heads. The sperm cells with foreign DNA incorporated by means of Ca++ and DMSO treatment still remain alive and mobile. The possibilities of mature sperms loaded with foreign DNA for the creation of transgenic mammals are discussed. PMID- 2238097 TI - [The cytogenetic effect of natural mutagenesis modifiers in a human lymphocyte culture. The action of aminobenzamide during the gibberellic acid induction of chromosome aberrations]. AB - The 3-aminobenzamide sensibilization of the cytogenetic activity of gibberellic acid in the culture of human lymphocytes has been investigated. Two-three-fold increase of the chromosome aberrations induced by gibberellic acid, irrespective of the time of 3-aminobenzamide addition to the cultures (the 28th, 46th, 72th hrs of the cultivation) is shown. PMID- 2238098 TI - [Chromosomal disorders in the oocytes of rats after stress exposure in the preovulatory period]. AB - Female rats at the stage of proestrus have been subjected to a stress effect- immobilization for an hour. Oocytes were cytogenetically analyzed and embryonal mortality was determined. It is shown that this stress effect at the end of the fist meiotic division of the oocytes increased the rate of aneuploid gametes and the level of embryonal mortality. PMID- 2238099 TI - [The cloning of "residual" DNA and the determination of the primary structure for the fragments of the barley-specific family of tandem repetitive sequences]. AB - High molecular weight "relic" DNA fraction can be separated from the bulk of barley DNA digested with different restriction enzymes by agarose gel electrophoresis. The majority of AluI-relic DNA clones contained barley simple sequence satellite DNA and other families of repetitive DNA. The clones representing HvRT family were sequenced. This family was found to be barley specific. It is composed of tandemly arranged 118-bp monomers and presents in 7 x 10(5) copies in barley genome. PMID- 2238100 TI - [A mathematical model of the proliferative kinetics of cells labelled with brominated DNA precursors]. AB - A mathematical model of cell division is presented. It permits analyzing cell proliferation obtained by using BrdU. Numerical experiments show that this model adequately describes experimental data. Application of this model permits decreasing experimental data bulk. PMID- 2238101 TI - [Aneuploidy in man (facts and hypotheses)]. AB - Mechanisms of the human aneuploidy formation are discussed proceeding from the review of the published data obtained by Soviet and foreign authors. It is supposed that hereditary determination of this process plays a main role as compared with new genomic mutations resulting from the induction by ecological factors. Microstructural rearrangements and nonhomologous recombination in nondisjunction of chromosomes during cell division are considered parallel with mosaicism as one of possible reasons of genetic predisposition. PMID- 2238102 TI - [The cytogenetic effects of 22-MeV neutrons]. AB - 22-MeV neutrons affecting the culture of human peripheral blood lymphocytes have been studied for their cytogenetic peculiarities. Linear character of the dependence of chromosome aberrations yield within the dose range of 0.2-4.0 Gy is noted. Relative biological efficiency of 22-MeV neutrons reaches the highest values at low doses (18.8-2.4). Pair fragments and dicentrics prevail in spectrum of aberrations. PMID- 2238104 TI - [The age-related and genotypic variability of the blood serum enzymes in swine at an industrial farm complex]. AB - Enzymes in pig blood serum have been studied for the dynamics of their activity as dependent on the breed peculiarities and production types. High correlations are revealed between the enzyme activity and the pig's fattening capacity as well as their stress-resistance. The use of the developed exponential functions makes it possible to achieve high probability (r = 0.88-0.89) in predicting meat and fattening capacities of pigs. PMID- 2238103 TI - [Genetic disorders in laboratory mice exposed in the area of the Chernobyl Atomic Electric Power Station]. AB - Laboratory male mice (CBA X C57Bl)F1 were exposed in three sectors with different contamination degree of radionuclides within 30 km-zone of the Chernobyl Atomic Power Plant. The total absorbed radiation doses in testes were 0.1; 3 and 25 Gy, respectively. Great depression of spermatogenesis was observed in exposed mice up to complete sterility in males from the most contaminated sector. The mutagenic effect of radiation was relatively low and did not increase with growth of the contamination degree. PMID- 2238105 TI - [The genomic organization and localization on the chromosomes of the HvRT family of DNA repetitive sequences in barley]. AB - HvRT family of repetitive DNA sequences from barley genome appears to have complex hierarchical organization. Tandem repetition of 118-bp monomers constitutes lower level of HvRT-family organization. Amplification units of the higher level consist of several contiguous 118-bp monomers. RFLP between different species and cultivars of barley resulted from the differences in the higher-order repeat structure. Individual chromosomes of barley contain specific HvRT subfamilies. This family also possesses separate domains differing in the restriction enzyme sites density. HvRT family is presented in the genomes of H. vulgare, H. leporinum, H. murinum, H. jubatum, but is absent in the genomes of H. marinum, H. geniculatum and wheat. PMID- 2238106 TI - [The lampbrush chromosomes of the chicken. Cytological maps of the macrobivalents]. AB - The lampbrush chromosomes (LBC) were prepared from growing oocytes 0.75-1.50 mm in diameter. A map of 6 autosomes and the ZW sex bivalents is presented. Several types of landmarks were noticed: lumpy loops (LL), telomeric bow-like loops (TBL), some large loops in interstitial regions (marker loops--ML). Supposedly, the centromeres of LBC in the chicken are at one of the axial bars bearing no loops. The landmarks PBL and DBL mark the proximal and distal boundaries of bars. LBC-A (probably, chromosome 1 of the chicken karyotype) is about 185 microns. There are 7.3 +/- 0.2 chiasmata. Chiasmata are distributed at quasi-random. In LBC-A one chiasma is localized in a telomere, as a rule. Coordinates of 13 of the 14 different landmarks in LBC-A have been estimated. LBC-B (probably, chromosome 2) is about 151 microns, there are 5.50 +/- 0.23 chiasmata. The LBC-B may be identified by LL-21 and LL-22. LBC-C (probably, chromosome 3) is 128 microns; there are 4.70 +/- 0.18 chiasmata. The chromosome can be identified by characteristic loops LL-31, an unlooped chromomere bar near the telomere (T-32), a characteristic distribution of normal loops along LBC-C: about one half of this LBC bears large loops, and the other one--small loops. LBC-D (chromosome 4?) is 107 microns; there are 3.80 +/- 0.31 chiasmata. Double-loop bridges appear frequently near ML-41. LBC-E (chromosome 5?) is about 72 microns with 2.50 +/- 0.28 chiasmata. There are characteristic TBL loops with abundant RNP material thus being like LL-loops. LBC-F (chromosome 8?) is about 36.5 microns; there are 2 chiasmata. This LBC can be identified by giant telomeric loops GML-F1 and by unlooped bar in the middle of LBC. PMID- 2238107 TI - [The differentiation of oval cells into hepatocytes during induced hepatic carcinogenesis in mice. An electron microscopic study]. AB - An electron microscopic study of murine oval cells, induced by a single injection of genotoxic agent dipin and by a partial hepatectomy, has shown that their ultrastructure and direction of differentiation depend on localization in the liver lobule. Oval cells around portal tracts go through three stages of development: low differentiated cells 4.40 +/- 0.51 mu in diameter with ovoid nuclei 3.43 +/- 0.44 mu, intermediate cells, and young hepatocytes. They form common ducts surrounded by a basal lamina, and produce bile canaliculi-like structures and intermediate junctions between them. Another part of the oval cell population is organized similar to the bile duct epithelium. It consists of cells 9.37 +/- 1.1 mu in diameter with nuclei 7.28 +/- 1.16 mu in diameter and form a system of branching and anastomosing ducts widespread along the parenchyma from the portal to the central veins. Our data indicate that the oval cells can differentiate into hepatocytes, and support a hypothesis according to which the cells of terminal bile ductules are liver epithelial stem cells which can differentiate into a hepatocyte or a bile duct cell lineage in periportal microenvironment. PMID- 2238108 TI - [Morphofunctional changes in the exocrine pancreatic cells in acute experimental pancreatitis in rats]. AB - Experimental pancreatitis was induced by cooling the splenetic part of rat pancreas with chlorethyl, and the cells of duodenal area of the pancreas were studied at different stages of pancreatitis using cytomorphometry, cytomorphology and autoradiography. Interlobular and interacinar oedemas were observed at the first hours after treatment. In 24 hours the intracellular oedema of exocrine pancreatic cells (EP) was detected. On day 14 after treatment typical acute edematous pancreatitis developed. The observed changes involve a pathological activation of EP of the duodenal area, a subsequent restoration of the structure of this area, and later a passage of pancreatitis into the chronic form. The usefulness of this model of pancreatitis for quantitative cytochemical studies of EP during pathogenesis and drug treatment is discussed. PMID- 2238109 TI - [The sensitivity to growth factors of NIH 3T3 cells transformed by the v-myc oncogene]. AB - Transformation of NIH 3T3 cells, induced by v-myc oncogene, activates a proliferative potential of the cells cultivated in the serum-free medium, and reduces the ratio of 3H-Tdr incorporation into the cells grown in the presence of 10% fetal serum in comparison to those grown in the serum-free medium. The v-myc transformed cells (NIH 3T3-v-myc) as well as the untransformed ones are very responsive to insulin. On the other hand, the epidermal growth factor, able to stimulate proliferation of NIH 3T3 cells, exert no effects on the NIH 3T3-v-myc cells. The NIH 3T3-v-myc cells cultivated in the medium, containing 2.5% human plasma enriched with thrombocytes, have the same proliferative characteristics as cells grown in the thrombocyte-free plasma. It is concluded that transformation of NIH 3T3 cells induced by v-myc oncogene may reduce a requirement for thrombocyte-released growth factors and EGF but not for insulin. PMID- 2238110 TI - [The cultivation of hybridoma cells in agarose granules]. AB - The results of cultivation of agarose gel immobilized hybridoma cells producing monoclonal antibodies to human alpha 2-interferon are presented. The immobilized cultured cells retained the higher viability for 10-28 days without changing the growth medium, in comparison with cultured cells in control suspension. The cells immobilized in agarose gel demonstrated a tendency to polyploidization as was revealed by the technique of DNA cytofluorimetry with Hoechst 33258. PMID- 2238112 TI - [The effect of the spontaneous level of the chromosome aberration rate on its alterations after a single local irradiation]. AB - With X-ray examinations of the stomach and duodenum, changes in chromosomal aberration frequencies in peripheral blood lymphocytes were shown to depend on the spontaneous level of these aberrations in patients exposed to a single local irradiation by 25 R. The cytogenetic efficiency of radiation exposure was found to be local in patients with the lower frequency of spontaneous chromosomal aberrations. A genetic genesis of the revealed dependence is supposed. The effect of irradiation on the correlation between radiosensitivity and radioresistance of the cytogenetic process is regarded as a possible mechanism of the appearance of the observed dependence. PMID- 2238111 TI - [Differences in the photodestruction parameters of flavin fluorescence in normal and tumor cells at a decreased pH of the incubation medium]. AB - Further investigation of the peculiarities of flavin fluorescence photodestruction in malignant cells was made. In normal cells incubated in low pH (3.0-3.2) physiological solutions, the decrease in the oxidized flavoprotein fluorescence intensity under irradiation is the same as in normal pH condition, whereas in tumor cell in low pH solutions a significant increase in the photodestruction level was noticed. The cells isolated from foci of transformation, following treatment of 3T3 NIH fibroblasts with the carcinogen N methyl-N'-nitro-N-nitrosoguanidine, displayed the photodestruction parameters similar to those in tumor cells. A two-step analysis of cells is proposed for distinguishing between the normal and malignant cells. PMID- 2238113 TI - [A flow diffusion chamber for research on cells in culture]. AB - A flow diffusion chamber designed for studying cells and tissues in culture is described. The chamber contains a plate with a great number of isolated holes, which enables one to perform the cultivation of cells at different distances from the porous membrane separating the cells from the perfused medium. An individual porous membrane can be placed above each hole. Evidence for the selective permeability of domestic membranes under the conditions of cell culture in chamber is presented. The chamber makes possible a simultaneous cultivation of a great number of various cultures with different conditions of mass exchange with common perfused medium, which contributes to intensification of studies. PMID- 2238114 TI - [An electron microscopic study of Cryptosporidium. II. The stages of gametogenesis and sporogony in Cryptosporidium parvum]. AB - The ultrastructure of stages of gametogony and sporogony of C. parvum from the intestine of experimentally infected suckling rats was studied by transmission electron microscope. Unlike merogony, in which the whole cytoplasm of the mother meront is used up for the merozoite formation, during microgametogony the large residual mass of gamonts remains in contact with the feeder organelle even after microgamete outbudding. Unlike other coccidia, during the microgametogenesis in C. parvum, the nuclear substance of the daughter nuclei is not separated into osmiophilic (containing the condensed chromatin) and achromatinic parts. The gamete outbudding in C. parvum is accompanied by evagination of the pellicle of the mother gamont whose cytoplasm displays some slit-like canals that seem to sequester the daughter nuclei with some portion of the surrounding cytoplasm. The flagella-free microgametes of C. parvum resemble somatic cells, rather than male sexual cells of other coccidia. The study of thick-walled oocysts of C. parvum made it possible to suggest that the fragile wall of the oocyst proper may be easily destroyed in the course of processing of the material to look eventually as a ghost of electron lucent substance in the parasitophorous vacuole, whereas the structures revealed on the electronograms may presumably represent the outer and inner layers of the sporocyst. If so, the suture described elsewhere in the cryptosporidial oocysts, is to be considered as belonging to the sporocyst wall rather than to the oocyst wall, i.e. likely as in other investigated coccidia. However, the question on the mode of sporozoite excystment in the thin-walled oocysts of C. parvum still remains obscure. PMID- 2238115 TI - [The effect of the disruption of the cytoskeletal elements on uncoupler-induced changes in the centrosome]. AB - The disruption of microtubules with nocodazole or microfilaments with cytochalasin B did not prevent mother centrioles from nonrandom, preferentially perpendicular orientation with respect to the substrate plane after FCCP treatment. The microtubules affect negatively the reorientation of centrioles, because after their disruption by nocodazole the percentage of centrioles with the perpendicular orientation (the angle is tipped to the substrate plane by over 74 degrees) is seen to increase. The microfilaments have the positive effect, because after their disruption by cytochalasin B the share of centrioles with the perpendicular orientation decreases. Thus, our observations do not support the hypothesis that the long microtubules can provide the perpendicular orientation of centrioles anchoring them in the cytoplasm. PMID- 2238116 TI - [Immunomorphological research on the formation of the extracellular matrix in epithelial cell cultures]. AB - Formation of extracellular matrix structures in cultures of rat liver epithelial nontransformed cell line IAR2 was studied with antisera to fibronectin, laminin and type IV collagen by immunofluorescence and immunoelectron microscopy of platinum replicas. Fibronectin formed peripheral spots of variable size some of which outlined free cell edges, as well as fibrils located towards the center of single cells or of cellular islands. Similarly distributed structures were seen in isolated matrices. Codistribution of fibronectin and actin was observed only for the peripheral line of fibronectin spots and marginal circular actin bundle. Basement membrane components. laminin and type IV collagen, formed mainly spots of variable size predominantly beneath the cell or each cell in an island. Occasional fibrils were seen also. Essentially the same results were obtained by immunofluorescence and immunogold electron microscopy. Cytochalasin D treated cells displayed spots of both fibronectin and laminin. The relevance of previously postulated receptor-mediated assembly of extracellular matrix structures to the epithelial cells is discussed. PMID- 2238117 TI - [The immunomodulation of the natural killer activity of the splenocytes in C3HA mice during hepatoma 22a growth]. AB - A single injection of C3HA mice with various immunomodulators-ds-RNA, thymogene (TM) and cyclophosphamide (CY)--performed one day before transplantation of syngeneic hepatoma 22a cells led to a decrease in the tumor growth rate. The most prominent effect was found following the CY treatment. The NK cell activity estimated per spleen of mice treated with ds-RNA and TM was seen increased in comparison with the control mice not given the modulators. The rate of tumor growth was due probably to this fact. The protective effect of CY may be accounted for by a direct action of this agent on tumor cells. PMID- 2238118 TI - [Chromosomal interrelations in the interphase nucleus]. AB - The distribution of prekinetochores in human lymphocytes has been studied by indirect immunofluorescence with autoantibodies against kinetochore. Lymphocyte flattening that allowed a 5-6 increase in their size, was suggested in addition to a method of lymphocyte stretching allowing a 10-fold extension. Prekinetochores in flat and stretched lymphocytes are seen settled down as separate pairs. The equal pattern of staining of these prekinetochores in each pair suggests that homologous chromosomes located in pairs. PMID- 2238119 TI - Tubercle 1978-1990. PMID- 2238120 TI - Factors of prognostic significance in Chinese children with tuberculous meningitis. AB - A study was undertaken to identify factors of prognostic importance for 199 Chinese children with tuberculous meningitis treated in Hong Kong between 1961 and 1984 inclusive. During the period under study rifampicin and then pyrazinamide were introduced into treatment regimens and intrathecal therapy was abandoned. An analysis of pretreatment characteristics and details of chemotherapy by multivariate logistic regression identified two independent variables that predicted prognosis, namely clinical stage at the time of diagnosis, and age. Changes in treatment policies and the introduction of new anti-tuberculosis drugs did not appear to influence prognosis. PMID- 2238121 TI - Chromosome damage in untreated tuberculosis patients. AB - The frequency of chromosomal aberrations and sister chromatid exchanges (SCEs) were estimated in the lymphocytes of 95 untreated tuberculosis patients to evaluate the chromosomal damage with reference to bacterial invasion. The frequency of chromosomal aberrations was significantly higher in tuberculosis patients compared to controls (p less than 0.001) while the SCE frequency did not show any statistically significant differences. These findings indicate that the basic mechanism of formation of chromosomal aberrations and SCE are different and they suggest that the tubercle bacillus might be capable of inducing chromosome damage. PMID- 2238122 TI - Sister chromatid exchanges in the lymphocytes of tuberculosis patients receiving short-term chemotherapy. AB - The frequency of sister chromatid exchanges was estimated in tuberculosis patients undergoing three different short term chemotherapy regimens (2SHRZ, 2HRZ and 2H2R2Z2), to evaluate the possible genetic damage caused by anti-tuberculous drugs. Of the three combinations studied, two combinations (2SHRZ and 2HRZ), which were administered daily, enhanced the frequency of sister chromatid exchanges significantly (p less than 0.05), while the third bi-weekly combination (2H2R2Z2) did not show any significant enhancement in the frequency of sister chromatid exchanges. These results are of importance in the treatment of tuberculosis, and indicate the need to select a drug combination that is equally efficient in the control of disease and at the same time less harmful to the genome of the patient. PMID- 2238123 TI - Evaluation of BCG at birth in the United Arab Emirates. AB - A total of 387 healthy full term infants who received BCG vaccination at birth were evaluated by the tuberculin PPD test at 6-8 weeks post vaccination. A total of 92% of these infants had visible BCG scars at that time. All infants were tested with PPD but only 264 returned for the test to be read. The tuberculin test was negative in 37 (14%) and of less than 5 mm induration in another 60 (23%) of the infants. The same pattern was observed in different nationalities. Of 11 infants with no BCG scar after vaccination, 3 had positive PPD reactions of more than 5 mm induration. There was a significant correlation between the size of the BCG scar and induration of tuberculin test P less than 0.001. The complications of the vaccination were minimal. We have observed 3 sterile abscesses at the site of BCG vaccination which resolved spontaneously. We think the available vaccine is safe and potent, and that the rate of BCG scar formation and of tuberculin conversion is higher than in most studies. PMID- 2238124 TI - Characterisation of plasmids extracted from AIDS--associated Mycobacterium avium isolates. AB - The plasmid profiles of 12 Mycobacterium avium strains isolated from 12 different patients with acquired immunodeficiency syndrome were analysed. Plasmids were identified in 9 of these strains. Plasmids were isolated from all 7 serovars 4 and 8 strains, a serovar 20a strain and an untypeable strain, but were not detected in either of 2 serovar 3b strains or an untypeable isolate. Southern blot hybridisations revealed that extracts derived from all of the plasmid containing strains hybridised to a DNA probe prepared from known mycobacterial plasmid sequences. However, restriction analyses suggest that native plasmids which hybridised to the DNA probe and were similar in mass were not identical. PMID- 2238125 TI - Tuberculosis in patients with various HLA phenotypes. AB - Tuberculosis patients and healthy subjects from six ethnic groups of the Soviet Union were HLA-A, -B, -C, and DR typed. The frequencies of the HLA-A, -B and -C antigens differed amongst the ethnic groups. With all groups, however, patients with tuberculosis showed a significantly increased frequency of HLA-DR2 and a reduced frequency of HLA-DR3 type. Unfavourable dynamics of tuberculosis was significantly associated with an increased incidence of B15 and DR2 and a reduced incidence of B27 and DR3. Family studies revealed that the inheritance of susceptibility to tuberculosis (from parent to offspring) is associated with the inheritance of certain HLA haplotypes. Tuberculosis patients bearing the DR2 antigen had increased levels of IgG antibodies to PPD and the frequency of B7 and, more particularly, DR2 was higher in anergic patients. PMID- 2238126 TI - In-vitro bacteriostatic and bactericidal activity of isoniazid on the Mycobacterium avium-Mycobacterium intracellulare complex. AB - Isoniazid inhibited the growth of Mycobacterium avium-Mycobacterium intracellulare strains at concentrations of 0.1-25 micrograms/ml and was even bactericidal for several strains. The bactericidal activity was observed in relatively susceptible strains. The susceptibility did not correlate with colonial morphology but correlated with species identification. Mycobacterium avium strains were more resistant to isoniazid than Mycobacterium intracellulare strains. PMID- 2238127 TI - Minimal bactericidal and inhibitory concentrations of ofloxacin on Mycobacterium fortuitum at pH 7 and 5: therapeutic implications. AB - Mycobacterium fortuitum infections of sternotomy wounds have been successfully treated with ofloxacin, a fluoroquinolone. We studied the MBCs and MICs in vitro of this antibiotic on the organism under neutral pH (7) and acidic pH (5) and found marked escalation of these values under the latter condition. This provides hints on the therapy of these infections under in vivo settings. PMID- 2238128 TI - Distribution of liposomes in tuberculous mice. AB - The dynamics of the distribution of liposomes for use as drug carriers for the treatment of tuberculosis is studied. While the free radiolabel injected into mice was rapidly excreted by the kidneys, the same label trapped within liposomes was retained for longer periods in the liver, spleen and lung. There were variations in the distribution and retention times of liposomes of different composition. When the distribution of liposomes in healthy and tuberculous mice was compared, a greater accumulation in the liver, spleen and lungs of healthy mice was observed, although the retention time in tuberculous mice was longer. These findings merit consideration in the design of therapies based on liposome entrapped drugs as the dynamics of distribution and retention differ between normal and infected animals. PMID- 2238129 TI - Differential effects of free and liposome encapsulated amikacin on the survival of Mycobacterium avium complex in mouse peritoneal macrophages. AB - Liposome-encapsulated amikacin shows significantly greater inhibitory activity against the survival of Mycobacterium avium complex inside mouse peritoneal macrophages than the free drug. Similar results were obtained whether the drug was added simultaneously with, 48 h prior to, or 48 h after the addition of mycobacteria to the macrophages. These observations support the hypothesis that the in vivo intravenous delivery of liposome-encapsulated amikacin results in the localization of the antibiotic in phagosomes containing mycobacteria inside resident macrophages of the liver and spleen. PMID- 2238130 TI - Cardiac tamponade due to tuberculous mediastinal lymphadenitis. AB - Pneumopericardium is rare in tuberculous mediastinal lymphadenitis. Much rarer is the association of pneumopericardium with cardiac tamponade. The case is reported of a 29-year-old patient in whom tuberculous mediastinal lymphadenitis resulted in a fatal tension pneumopericardium. PMID- 2238131 TI - Tuberculosis of the breast: a rare modern disease. AB - A case of mammary tuberculosis is reported. A communication between the axillary glands and the breast emphasises Cooper's theory that the breast becomes secondarily involved by lymphatic extension. Involvement of other organs by acid fast bacilli could not be demonstrated. A relapse occurred sixteen months after a 6-month course of treatment with rifampicin, isoniazid, ethambutol and pyrazinamide. PMID- 2238132 TI - Hepatic tuberculosis; a rare case of bleeding gastric varices. AB - A laparotomy was performed on a 68-year-old female who, in spite of medical treatment, suffered from uncontrolled upper gastrointestinal bleeding due to ruptured gastric varices. Histological examination of the liver tissue taken during operation revealed tuberculosis. Hepatic tuberculosis, although rare, should be kept in mind as one of the differential diagnosis when there is unexplained, noncirrhotic bleeding gastric varices. PMID- 2238133 TI - Primary tuberculosis of the penis in an infant. AB - Primary tuberculosis of the penis with associated bilateral inguinal lymph node enlargement and a discharging sinus is described. Its rarity is emphasized and its likely mode of transmission is also highlighted so that it can be looked for in areas where infantile circumcision is practised, particularly in developing countries. PMID- 2238134 TI - [Current role of diagnostic isotopes in cardiology]. PMID- 2238135 TI - [Treatment of Basedow's exophthalmos]. PMID- 2238136 TI - [Bladder exstrophy. Analysis of 50 cases]. PMID- 2238138 TI - [Primary small bowel tumors (lymphomas excluded). Report of 19 cases (1978-88)]. PMID- 2238137 TI - [Surgical treatment of bronchiectasis]. PMID- 2238139 TI - [Congenital pulmonary emphysema in children: report of 19 cases]. PMID- 2238140 TI - [Systematic titers in syphilitic serology: a prospective study]. PMID- 2238141 TI - [Hypertension in the older patient]. PMID- 2238142 TI - [Nutrition of the pregnant woman and the infant's birth weight]. PMID- 2238143 TI - [Pompe's disease: a report of 3 cases (clinical, biochemical, anatomo pathological study]. PMID- 2238144 TI - [Splenic and mesenteric arterial hydatic emboli secondary to a primary hydatic cyst of the thoracic aorta]. PMID- 2238145 TI - [Plasma cell granuloma and pulmonary fibroxanthoma: report of 2 cases]. PMID- 2238146 TI - [The effect of mepacrine and propranolol on lipid level in the alveolar surfactant during anaphylactic shock]. AB - It is shown that the development of anaphylactoid shock in rats is connected with a decrease of the surface activity of alveolar surfactant and liberation of arachidonic acid from pulmonary surfactant phospholipids. Preventive injection of lipomodulators--A2 phospholipase inhibitor (mepacrine) or triglycecolipase inhibitor (propranolol)--to animals normalizes the level of lipids in the surfactant and blocks liberation of arachidonate and palmitate from surfactant phospholipids in an anaphylactoid shock. PMID- 2238147 TI - [Increase in free Ca2+ level determined by quin-2 in spleen lymphocytes from irradiated rats]. AB - The output of lymphocytes, obtained on a ficoll-verografin gradient and intracellular free Ca2+ concentration were studied in the rat spleen 1, 3 and 6 days after X-ray irradiation in a dose of 0.5 Gy. The amount of lymphocytes decreased by 30% a day after irradiation and turned to the control level 3 days after exposure of animals. Free Ca2+ concentration remains abnormally high during all the examined period, increasing to 411 nM a day after irradiation and approaching to the control value 6 days after irradiation. PMID- 2238148 TI - [The effect of sodium nitrite, stable radical of 4-hydroxy-2,2,6,6 tetramethylpiperidin-1-oxyl and their mixture on methemoglobin formation]. AB - Sodium nitrite oxidizes the mice hemoglobin in vitro. The stable radical 4 hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl inhibits the process of oxidation. This effect is achieved when the radical is introduced into the system before sodium nitrite. The same effect is achieved in vivo. The level of methemoglobin is not influenced when mice get only the radical in comparison with the control group. We have not found the changes in the level of carboxyhemoglobin in the groups of mice that got the sodium nitrite, the radical and their mixture in comparison with the control group. PMID- 2238150 TI - [Characteristics of brain gastrin/cholecystokinin-binding proteins]. AB - Gastrin/cholecystokinin-binding proteins were purified using the column affinity chromatography on immobilized pig tetragastrin and cholecystokinin. Immunoblotting analysis of different human tissue extracts with specific antisera obtained against gastrin-binding proteins was performed. It was found that high molecular weight polypeptide zones of 120 kDa and 35 kDa were characteristic of the brain only. Autoantisera of patients with type A gastric disease reacted with some gastrin/cholecystokinin-binding proteins in human brain and mucosa including human brain polypeptide of 120 kDa. It is supposed that there are neurospecific gastrin-binding proteins (possibly gastrin/cholecystokinin receptors in the brain). PMID- 2238149 TI - [Minor peptides of animal proteins as antibiotics and possible factors of nonspecific immunity]. AB - Screening of more than twenty short synthetic peptides characteristic of different proteins has revealed antimicrobial activity of the KRFAE peptide--from human preproenkephalin A against gram-negative bacteria. Modification of the peptide structure by means of administration of d-amino acids has permitted obtaining dKRFdLE analogue with the expressed and stable antimicrobial activity in vitro when growing bacteria on the minimum glucose-mineral medium. Changes and rearrangements of aminoacids in the dKRFdLE peptide in the second, third and fourth positions sharply decreased anti-microbial activity. The weaker antimicrobial activity as compared with that in dKRFdLE was peculiar to peptides with the other primary structure. Possible participation of peptides as antibiotics in the mechanisms of nonspecific immunity as well as the methods of their rational search are discussed. PMID- 2238151 TI - [Adenylate cyclase and adrenoreceptors in the myometrium]. AB - Data are presented on the content and hormonal regulation of alpha- and beta adrenoreceptors in myometrium, interrelation of adrenoreceptors with adenylate cyclase and contractile state of myometrium. Processes in the structure of adenyl cyclase complex during the enzyme desensitization have been discussed. PMID- 2238152 TI - [Composition and physical structure of atherogenic lipoproteins in ischemic heart disease]. AB - The results of comparative studies in atherogenic lipoproteins of blood plasma under heart ischemic disease (HID) which is accompanied by hypercholesterinemia or proceeds without disturbances in the lipid metabolism, evidence for considerable differences in the composition and physical structure of very low density lipoproteins (VIDL) and low-density ones (LDP) under the investigated states. The decrease in the surface charge density and in sizes of VLDL, as compared to normal, which are least expressed at HID and an increase in the surface charge density with certain increase of LDL radii under this pathologic state are revealed. PMID- 2238153 TI - [Properties of a complex of nonspecific esterases from the green oak roller moth]. AB - A complex of nonspecific esterases of green oak roller moth is represented by of series of multiple forms including carboxyl-, acetyl-, aryl-esterase and esterase with mixed properties. Esterases characterized by different substrate specificity and belonging to different types change their activity in the insect ontogenesis. The authors have established the interaction of esterases with the secondary metabolism substances large amounts of which are concentrated in the oak leaves. PMID- 2238154 TI - [Isoenzyme spectrum and kinetic properties of pyruvate kinase from the liver of thiamine-deficient rats]. AB - Thiamine-deficiency in animals induced by everyday subcutaneous administration of oxythiamine in a dose of 4, 40 and 100 mg/kg of weight for 10 days results in a decrease of the total activity of pyruvate kinase in the liver tissue and does not affect the mentioned index in the kidney and heart tissues. It is shown that as a result of the enzyme fractionation in the column with DEAE-cellulose the total activity of pyruvate kinase in the liver tissue of rats with thiamine deficiency decreases due to L-isoform while the content of M-isoform remains unchanged. Thiamine deficiency does not affect kinetic characteristics of the L isoform, extracted from the liver and this shows the absence of changes in the degree of phosphorylation of pyruvate kinase L-isoform under these conditions. PMID- 2238156 TI - [The effect of pH on the passive transport of Ca2+ by membranes of fragmented sarcoplasmic reticulum of skeletal muscles]. AB - The initial rate of Ca2+ translocation in vesicular preparations of the sarcoplasmic reticulum membranes is shown to fall with a pH decrease to 6.0 or 5.0 and to rise with a pH change to 7.0 to 7.8 in respect to the initial 6.5. It is established that the Ca2+ sorption by the membranes or their fluidity make no essential contribution to the recorded changes of 45Ca2+ level in the membrane preparations. It is shown that the passive Ca2+ transport depends to a considerable extent on the concentration of a proton at the outer surface of the sarcoplasmic reticulum membrane: an excess of H+ inhibits the Ca2+ input and output, while a decrease of the proton concentration promotes an increase in the rate of these processes in the sarcoplasmic reticulum. PMID- 2238155 TI - [Activity of neutral peptide hydrolases and oxidative enzymes in the myocardium and blood during hypoxic hypoxia]. AB - The citric cycle dehydrogenases and neutral peptide hydrolases (NPH) activity was determined in the myocardium and blood serum of Wistar rats under acute and prolonged hypoxic hypoxia. It was shown that the NPH activity and the activity of the most oxidative enzymes change in the same direction during adaptation to the high-altitude conditions. The role of the NPH in the oxidative metabolism reconstruction under acute and chronic hypoxia was discussed. PMID- 2238157 TI - [Spectral-fluorescent characteristics of rat transcortin in normal conditions and during experimental circulatory insufficiency]. AB - Spectral-fluorescent parameters of rat transcortin isolated from blood plasma of intact rats and rats with circulatory insufficiency were studied. The differences in the Schtern Folmer constants and the dissociation constants for the transcortin-corticosterone complex obtained during the protein titration by corticosterone may be due to different tryptophanyl surroundings in the molecules of the studied proteins. This may be a consequence of the conformational rearrangements of the corticosteroid-binding globulin molecules. PMID- 2238159 TI - [The effect of hypoxic hypoxia on the activity of glycolysis enzymes in rat erythrocytes]. AB - The oxygen-binding properties of hemoglobin, concentration of 2,3 diphosphoglycerate, activity of carbohydrate metabolism enzymes and kinetics of rat erythrocyte hemolysis have been studied at high altitudes. The hemoglobin affinity to oxygen, glycolysis enzyme activity and erythrocyte membrane resistance are established to increase at the initial period of adaptation. The activation of the pentose-phosphate pathway of the glucose, transformation and inhibition of the glycolytic process in these cells are observed on the 10th day. PMID- 2238158 TI - [Activity and properties of L-lysine amidase in Salmonella strains]. AB - Distribution, activity level and properties of alpha-lysinamidase have been studied in Salmonella strains. The Km value for L-lysinamide was calculated to be 4.2 mM and for L-alpha-aminocaprolactame--5.1 mM. This enzyme, parallel with lysinamide, catalyzes hydrolysis of alpha-aminocaprolactam and leucinamide. Asparagine, glutamine, caprolactam, triptophanamide were not lysinamidase substrates. PMID- 2238160 TI - [The effect of alpha-ketoglutarate, malate and alpha-glycerophosphate on bioenergetic processes in ischemic myocardium]. AB - Anti-ischemic action of exogenous natural metabolites and their effect on biological combustion processes indexes in cardiac muscle has been investigated on white rats with the experimental myocardial infarction. It has been established that the marked cardioprotective effect of malate and alpha ketoglutarate is associated with the glycolysis and enzymes activation of creatine kinase system of energy transport. At the same time malate activates pentose-phosphate cycle and tissue respiration enzymes. alpha-glycerophosphate displays definite anti-ischemic properties not associated with the intervention into biological combustion processes. PMID- 2238161 TI - [Dynamics of lipid peroxidation and steroidogenesis in adrenal cortex during stress]. AB - The phase character of lipid peroxidation has been found in the rabbit adrenal cortex in the process of adaptation to extreme loads. Under acute stress the activation of lipid peroxidation is directly dependent on the hormonal synthesis processes. Under conditions of the prolonged stress factor an enhancement of the lipid peroxidation intensity in the adrenal cortex coincides with a decrease in the steroidogenesis rate. PMID- 2238162 TI - [Survival of the unsatisfied?]. PMID- 2238163 TI - [Space medicine]. PMID- 2238164 TI - [Schizophrenia: an organic disease? Current status and debate]. AB - Schizophrenia may be interpreted as a group of conditions with various etiologies and pathogeneses but with common clinical features. In chronic forms with negative symptoms, CT scanning reveals atrophy of the brain. Other imaging techniques such as MR and PET confirm these findings and neurochemical, physiological and anatomical investigations demonstrate, similarly, that organic changes in the brain occur in patients with schizophrenia. The changes are probably due to a developmental defect and not to tissue degeneration. The results of the numerous neuroscientific investigations suggest that the therapeutic contributions for schizophrenia should have altered priorities. Medical therapy and psychotherapy must be supplemented by neuropsychological and social rehabilitation. Prophylaxis and early diagnosis will probably be possible in the near future so that the poor prognosis of this disease may be altered. Danish psychiatry is still characterized by development in neuroscience to a limited extent on account of marked technological delay. Establishing of a neuropsychiatric speciality now opens an interesting future perspective. PMID- 2238165 TI - [Prostatic cancer and growth factors]. AB - Advanced prostatic cancer (PC) involves a serious prognosis. PC cells form growth factors, which affect growth in autocrine or paracrine manner. PC cell lines, hormone dependency, and growth modalities are mentioned. Interference with these model systems by TGF-alpha, TGF-beta and EGF is described. The presence of less characterized growth factors in homogenates and conditioned media from PC cells is mentioned. An abundance of EGF and EGF-receptors has been found in PC compared to BPH samples. New strategies for treatment are outlined. PMID- 2238166 TI - [Social situation of the 70-year old population in the past and present. A cohort comparison of 70-year old men and women born in 1987 and 1914 in Glostrup]. AB - A cohort comparison between two different populations of 70 year-olds in Glostrup studied in 1967 (230 men and 210 women) and in 1984 (412 men and 392 women) was conducted for the purpose of identifying differences in social background factors known to have influence on health and the quality of life of old people. The findings show, that from 1967 to 1984, the standard of housing had improved. Significantly more 70 year-olds had better housing conditions with bath, toilet, kitchen and central heating in 1984 (65-92%). Women in the 1914 cohort had significantly longer education and a larger proportion were employed outside the home than in the 1897 cohort. Another significant cohort difference found was a tendency toward earlier retirement in the order of 2-3 years. This was seen for both sexes and all occupational groups. Since the two populations of 70 year-olds in Glostrup differ with regard to both social conditions and on health variables, this cohort comparison offers a useful starting point for research on how living conditions in combination with other factors affect health and aging. PMID- 2238167 TI - [Health status of the 70-year-old population in the past and present. A cohort comparison of 70-year old men and women born in 1987 and 1914 in Glostrup]. AB - A cohort comparison between two different populations of 70 year-olds in Glostrup who had health examinations in 1967 (230 men and 210 women) and in 1984 (412 men and 392 women) was conducted with the purpose of describing changes in health variables among old people during a period of falling mortality for both men and women. From the 1967 investigation to the 1984 investigation there was a significant improvement of the cardiovascular risk profile (i.e. body mass index, blood pressure, serum cholesterol, glucose tolerance) which is consistent with other such investigations. In contrast to these findings, symptoms of chronic conditions (angina pectoris, intermittent claudication and bronchitis) as well as the need for health care were the same in the two populations of 70 year-olds. In addition, the 1914 cohort reported a more pessimistic outlook with regard to their general health and greater consumption of medicine. The results of this investigation are consistent with expectations regarding changes in risk factors and mortality in older generations. The consequences of the falling mortality for morbidity and functional ability in a life perspective are, however, still uncertain, and cannot be evaluated alone from results such as these. PMID- 2238168 TI - [Epidemiology of burns. A follow-up from a 20-year period at Odense hospital]. AB - The numbers of patients admitted with burns, as an expression of the incidence of burns, registered in the Burns Unit, Odense University Hospital were compared for two ten-year periods: 1968-1977 and 1978-1987. A total of 1,548 hospitalized patients were involved. The etiology of the accidents, distributed according to sex, age and degree of severity and the number of deaths were calculated. A significant decrease in the total number of burning accidents was demonstrated, mainly due to the decrease in children aged 0-5 years and 6-15 years. Where the youngest children were concerned, this decrease was due to a decline in the number of scalds but also because of reductions in the number of contact burns and electrical and corrosive injuries. This was corrected for the altered age distribution with relatively fewer children during the second decade. PMID- 2238169 TI - [Quality of life of hemodialysis patients before and after erythropoietin therapy. A double-blind, randomized, placebo controlled study]. AB - In a double-blind, placebo-controlled trial of rHu-EPO (recombinant human erythropoietin) comprizing 19 haemodialysis patients (rHu-EPO: n = 9, placebo: n = 10) the patients' opinion about the influence of the treatment on the quality of life was investigated. At the commencement of the trial and after eight weeks, a score was registered by means of a structured interview with a range of 0-10 concerning the complaints most frequently expressed by haemodialysis patients. Erythropoietin was effective in the treatment of renal anaemia. In the therapeutic group, the mean haematocrit value increased from 0.206 to 0.338 (p less than 0.0005), while no change in the haematocrit value was observed in the placebo group. In the therapeutic group, significant decreases were found in the interview scores for fatigue, vertigo (p less than 0.001), dyspnoea (p less than 0.0025), muscular weakness (p less than 0.01) and palpitations (p less than 0.05). No significant differences were found in the placebo group. The treatment had no serious side-effects. On the basis of this material, it is concluded that erythropoietin treatment of haemodialysis patients is effective and that a marked improvement in the quality of life can be observed already after treatment for eight weeks. PMID- 2238170 TI - [Complications caused by intrauterine contraceptive devices]. AB - During the period 1981-1982, IUDs were introduced in 1,697 women in the Advisory Clinic for Contraception in the County of Arhus. The course in a period of six years after this was investigated retrospectively in view of the frequencies of complications. A total of 459 IUDs were either lost or had to be removed on account of haemorrhage/pain, infection or pregnancy. Where all types of complications were concerned, higher frequencies of complications were encountered in the younger age groups and in nulliparous women. The dependence of the frequency of complications on the age of the patients was most marked among women who had borne children previously. In the total population, 29% of the women had the IUD removed within a period of three years. In women under the age of 20 years, 45% were removed and, in women over the age of 35 years, only 18% were removed during the same period. The total pregnancy risk was 2.7/100 women after use for two years and 3.2/100 women after three years. In contrast to this, the risk in women under 20 years was 6.6/100 women and 10.8/100 women after use for two and three years, respectively. On account of a high frequency of infection, increased tendency to extrusion and poor effectivity, the use of IUDs in young nulliparous women is not recommended. PMID- 2238171 TI - [Intracavernous self-injection for treatment of erectile dysfunction inpatients with spinal cord injuries]. AB - Twelve patients (aged 18-70 years, average 41 years) with known spinal cord lesions with durations of 1-25 years and with levels of the lesions from C II incomplete to L III complete received intracavernous injection of papaverine with a commencing dose of 15 mg papaverine. Following this, nine patients could obtain usable erection lasting from 30 to 300 minutes with doses from 15-60 mg. In one patient, however, 60 mg papaverine was supplemented by 5 mg phentolamine. The patients were then trained in the technique of self-injection. On contact 1-37 months after the primary instruction, eight patients had performed a total of 40 self injections with the object of coitus, which was successful in all of the cases. Because he had no partner, one patient had no employed self-injection but would like to employ the method if the appropriate situation arose. Two patients did not want to continue self-injection. One of these considered that the method was too complicated to use and the other had had an episode of prolonged erection requiring treatment. No other side effects requiring treatment were observed. The relationship to possible partners and the experience of libido, "orgasm" and feeling of self esteem as compared to previous experiences were registered. Six out of nine patients had experienced improvement in at least one of these fields and none had experienced deterioration. A total of seven patients planned to employ the method in future. The authors conclude that self-injection of papaverine is a promising supplement in the treatment of erective dysfunction in patients with spinal cord lesions. PMID- 2238172 TI - [Vasectomy in specialized surgical practice]. AB - In the county of Roskilde an exception was made from the Danish legislation concerning sterilization that vasectomy should be performed in hospitals only on account of the long waiting list for this intervention. Two surgical specialists were selected to perform the operation in their practices. 88% (176/199) elected to accept the offer. All of these sterilizations were carried out within a period of six months. A questionnaire investigation did not reveal any difference in satisfaction between conduct of the intervention by the practising specialist in surgery or in hospital. Justification of the requirement that this form of sterilization can only be undertaken in hospital is discussed. PMID- 2238173 TI - [Spontaneous perforation of the biliary tract during the neonatal period]. AB - Spontaneous perforation of the biliary passages is a rare condition during the first months of life. The course of the condition may be acute or more chronic. The symptoms are jaundice, clay-coloured stools, dark urine, distended abdomen, regurgitation and failure to thrive. The diagnosis can be established by scanning of the abdomen and 99mTc-HIDA-scintigraphy of the biliary passages. The perforation is usually found to be localized to the transition between the cystic duct and the common hepatic duct and is probably due to a localized development defect in the biliary passages. Operation is always required. The prognosis is good and the infants do well after operation. PMID- 2238174 TI - [Congenital duodenal obstruction caused by an abnormal superior mesenteric vein]. AB - A case of congenital duodenal obstruction caused by an abnormal superior mesenteric vein is presented. The obstruction was successfully treated by duodenoduodenostomy anterior to the vein. PMID- 2238175 TI - [Prevention--need for periodic ophthalmologic examinations of diabetics]. PMID- 2238176 TI - [Thyroid surgery]. PMID- 2238177 TI - [Discharge records as information sources]. PMID- 2238178 TI - [Can ultrasonic scanning replace phlebography in the diagnosis of deep thrombophlebitis of the leg?]. AB - Until recently, phlebography with contrast agents has been the standard method for demonstration of deep venous thrombosis in the lower limb (DVT). In recent years, however, this has been replaced to an increasing extent by ultrasonic scanning. In contrast to radiographic examination, this method does not require injection of a contrast agent and it does not employ ionizing irradiation. The principle of ultrasonic scanning is that a normal vein may be compressed flat by means of slight pressure from the transducer whereas a vein filled with thrombi cannot be compressed. Ultrasonic examination is not (yet?) of diagnostic value in the leg but, more centrally, it is of the same diagnostic value as radiographic examination. It is suggested that ultrasonic scanning can replace phlebography in patients with their first DVT. If this gives a negative result, it may possibly be supplemented by phlebography of the veins of the leg. PMID- 2238179 TI - [Evaluation of the discharge summary by general practitioners. A questionnaire study]. AB - In March 1986, a questionnaire investigation was sent to 250 general practitioners chosen at random in Denmark. In this questionnaire, general practitioners were asked about their assessment of the total activity involved in letters of discharge. Out of the practitioners questioned, 188 replied to the questionnaire (75.2%). 74% of the practitioners considered that changes were necessary in discharge letters. Most dissatisfaction was expressed about late receipt of discharge letters. 34% of the practitioners found that these letters should be received 0-3 days after discharge of the patient while 61% considered that 4-7 days after discharge could be accepted. A total of 92% considered that, on an average, they received letters of discharge later than seven days after discharge of the patient. As regards the contents of the letters of discharge, 68% of the practitioners considered that these were usually satisfactory. Practitioners appreciated substantial letters with emphasis on conditions of significance for the post-hospital treatment. The most important information was considered to be: medicine on discharge, information given to the patient, reasons for possible changes in medication, information about the subsequent treatment in addition to medicine and information about patho-anatomical findings at operation or biopsy. This investigation has provided a general consumer review of the form of discharge letters, the language, content, use and time of sending. PMID- 2238180 TI - [Evaluation of the discharge summary by physicians in charge. A questionnaire study]. AB - In September 1986, a questionnaire about letters of discharge was sent to 250 physicians-in-charge i 250 clinical hospital departments in Denmark. Out of these, 214 replied to the questionnaire (85.6%). Only 110 (51%) of the physicians in-charge stated that there was a definite time (number of days) by which the letter of discharge should be sent after the discharge of the patient. In 99 departments (46%), the letters of discharge were, on an average, sent later than the physician-in-charge found acceptable. 50% of the physician-in-charge found that the acceptable time of sending the letter of discharge after discharge of the patient was 0-3 days. 43% of the physicians-in-charge found that 4-7 days after discharge of the patient could be accepted. Formalized teaching in writing letters of discharge only took place in 24 departments (11%). Only few physicians in-charge stated that they often or fre quently received negative or positive feed-back from general practitioners about letters of discharge. The following concrete proposals to improve the quality of letters of discharge and to shorten the time until sending are discussed: simplifying the passage from dictation of the letter to dispatch, increased formalized teaching of house officers and generally higher priority for letters of discharge. PMID- 2238181 TI - [Evaluation of the discharge summary by resident staff physicians. A questionnaire study]. AB - In September 1986, a questionnaire about letters of discharge was sent to 250 house officers in 250 clinical departments in Denmark. Out of these 197 replied to the questionnaire (78%). 32% of the house officers found that an acceptable time for the general practitioner to receive the letter of discharge was 0-3 days after discharge of the patient, while 53% of the house officers found that 4-7 days time was acceptable. 23% of the house officers stated that they had now or previously received formalized teaching about how to write letters of discharge. 44% of the house officers stated that they never received criticism or advice about writing of letters of discharge from their physicians-in-charge. The house officers considered that the most important information in the letter of discharge was, in general: medication on discharge, recommended follow-up treatment apart from medicine, information about possible outpatient visits, pathological findings at operation or biopsy and information about the treatment during hospitalization. 88% of the house officers considered that the letter of discharge was a good form of communication. 29% of the house officers considered that alterations of the work in toto of the letters of discharge were necessary and remarked that this was particularly important as regards early dispatch of letters of discharge to general practitioners. A description of the function of letters of discharge as seen by house officers is attempted in this investigation. PMID- 2238182 TI - [Epicrisis. A report from the county of Copenhagen]. AB - During a random week in 1987, 35% of the general practitioners from all of the municipalities in the County of Copenhagen participated in a questionnaire survey whose objective was to illuminate the quality, expedition time, and possible problems associated with the letter of discharge (LD), an important link between the primary and secondary medical services. It can be concluded that the expedition time for a large number of LD's from the hospitals of Copenhagen County is unacceptably lengthy. A surprisingly large number of patients visited their own general practitioner during the week following discharge with questions about the information which had been given them during their hospital stay, regardless of agreements for ambulatory monitoring at the department from which they had been discharged. A preliminary LD can, to a certain extent, alleviate the problems brought about by the lack af an LD but ought not to replace or delay the issuance of the actual LD, and is a more expensive solution. The quality and content of the LD can be evaluated generally as good, but could be improved if the recommended follow-up treatment and information to the patients and relatives is routinely carried out. PMID- 2238183 TI - [The patterns of anxiety and crying among normal Danish infants with and without colic]. AB - On the basis of a descriptive, prospective investigation, the patterns of fussing and crying in normal Danish infants aged from 2-3 to 14 weeks are described. A total of 102 infants were included in the investigation and 85% completed the investigation. The parents carried out daily registration of the periods of fussing and crying. The great majority of the infants were very placid. The mean duration of fussing for the entire group was half an hour per week during the third week of life. This increased to 2 1/2 hours per week at the sixth week of life and then decreased gradually to 0 hours per week from the 12th week of life. The material was subdivided into quartiles. Infants in the first and second quartiles showed practically no fussing. Infants in the third quartile were fussy at the commencement of the period and became gradually more placid from the fifth week of life. Infants in the fourth quartile were fussy during the first 9-10 weeks of life, after which the fussing gradually diminished. In infants in the third and fourth quartiles, fussing was most marked in the evenings. Two pairs of parents considered that their infants had colic. Ten infants were defined as having infantile colic. In these infants, the patterns of fussing and crying showed a common pattern and this was significantly different from the remainder of the group. The basic variables for the 25% most placid infants and the ten infants presumed to have colic are compared. PMID- 2238184 TI - [The optimal dose of bendroflumethiazide in hypertension. A randomized double blind dose-response study]. AB - The object of this study was to determine the clinically relevant dose of bendrofluazide for the treatment of arterial hypertension. A material of 257 male and female subjects, age 25-70 years, with sitting diastolic blood pressures between 100-120 mmHg after six weeks of placebo treatment participated in this randomized, double-blind placebo-controlled parallel group study. The patients were treated with either 0, 1.25, 2.5, 5.0 or 10 mg bendrofluazide daily for 12 weeks. Blood pressure was measured with a random zero sphygmomanometer and a Tricuff. Compliance was checked by tablet counts. The mean decreases in diastolic blood pressure were 3.5, 9.8, 10.8, 10.1 and 10.8 mmHg in the five treatment groups respectively. The heart rates were unchanged in all groups. Dose-effect relations were demonstrated for potassium, urate, glucose, cholesterol and apolipoprotein B. The lowest dose of bendrofluazide, 1.25 mg, affected only urate, whereas all of the mentioned biochemical variables were affected by the highest dose of 10 mg. It can be concluded that the optimal dose of bendrofluazide for aterial hypertension is 1.25 mg daily. Increase in the dose beyond this level only results in more pronounced adverse biochemical effects including the lipid-metabolism and subjective adverse events. PMID- 2238185 TI - [Spirapril and nitrendipine in arterial hypertension. A comparison of therapeutic effects and tolerance]. AB - In a double-blind, randomized parallel-group investigation, a new angiotensin converting enzyme-inhibitor, spirapril, was compared with a calcium antagonist, nitrendipine, in 266 patients with mild to moderate hypertension (diastolic blood pressure 96-119 mmHg). The object was to reduce the diastolic blood pressure measured 24 hours after intake of medicine to less than or equal to 90 mmHg. After monotherapy for four weeks with either 20 mg nitrendipine once daily or 12 mg spirapril once daily, the dosages were doubled in the patients in whom the desired blood pressure had not been obtained. After treatment for eight weeks, 12.5 mg hydrochlorthiazide daily was employed as a supplement in patients who had not yet obtained satisfactory blood pressures. Both methods of treatment resulted a lower number of patients who responded and lesser decreases in blood pressure than anticipated. No differences were found in the decreases in blood pressure resulting from the two therapeutic methods. The effect of supplementary hydrochlorthiazide to spirapril treatment was as anticipated while the combination with nitrendipine only resulted in a marginally extra decrease in blood pressure. Nitrendipine resulted in significantly more side effects and more patients defected from the investigation on account of side effects in the nitrendipine group (27%) than in the spirapril group (7%). This investigation had documented the abilities of nitrendipine and spirapril to reduce blood pressure and the side effects associated with this but does not predict whether the preparations can be employed to prevent the complications of hypertension which constitute the indications for treatment. Supplementing nitrendipine therapy with hydrochlorthiazide is not recommended. PMID- 2238187 TI - [Pain and dysesthesias in the mastectomy scar]. AB - With the object of investigating the occurrence of pain and dysaesthesiae in the scar following mastectomy, 120 were interviewed by a standard questionnaire in a prospective study. These women had commenced postoperative control or treatment in the Department of Oncology in the University Hospital of Aarhus consecutively during a one-year period. One hundred and ten of these women were interviewed again one year later. In 92% of the patients with scar pain and dysaesthesiae, these appeared within the first three months postoperatively. At the first interview, 42 patients (35%) had scar pain and 15 of these (13%) experienced constant scar pain. One year later, 25 patients (23%) still had scar pain and 13 patients (12%) had experienced persistent scar pain throughout the entire year. Two of the patients (8%) with scar pain had constant pain while, at the second interview, 14 patients (56%) reported that the scar pain lasted for seconds. Twenty-seven patients (23%) had dysaesthesiae at the first interview while 29 patients experienced these continually one year after operation. Both the intensity and the duration of the scar pain diminished with the elapse of time. This held also true where dysaesthesiae were concerned but was not so marked. PMID- 2238186 TI - [Measurement of systolic finger blood pressure with a pulse oximeter]. AB - In order to investigate whether the pletysmographic curve on a pulse oximeter can be employed for measurement of the systolic finger blood pressure, the authors compared the method with a strain-gauge method and undertook 160 measurements with a finger cuff on 11 healthy volunteers. By varying the pressure in two cuffs placed on the arm, the blood pressure in the finger could be altered from normal to very low values. The difference between the connected values was analysed and it was found that the difference between strain-gauge and pulse oximeter measurements read on the printer on employment on a new volunteer will be -0.9 +/ 3.8 mmHg. If the blood pressure is read on a manometer, the same difference will be -1.5 +/- 5.2 mmHg. The authors consider that the method is interesting in view of future employment for assessment of the collateral circulation in the hand but they recommend further investigations on patients with occlusive arterioschlerotic disease in the upper limbs. PMID- 2238188 TI - [Human milk substitutes based on cow's milk]. PMID- 2238189 TI - [Prevention of allergy. Guiding norms]. PMID- 2238190 TI - [Continued education course on the problems of sleep apnea and snoring, Uppsala, 21-23 March 1990]. PMID- 2238191 TI - [Cesarean section--why such variations in frequency?]. PMID- 2238192 TI - [Health screening in the workplace. Benefits and principles]. AB - This article describes the prophylactic programmes for health surveillance which exist in the occupational environment in Denmark. Compared with other industrialised countries, Denmark has only few established surveillance programmes. Nevertheless, these investigations exist, particularly in the form of non-specific general clinical health investigations at local workplaces, in certain branch agreements and in certain types of work. In addition, the article provides a review of the literature concerning health and health-economic effects of supervision of health. It is concluded that with the existing knowledge, pre employment examinations and periodic health examinations as routine examinations without and clearly defined object must be regarded as having limited prophylactic value and that examinations of this nature can scarcely give the worker any health benefit or give the employer any economic profit. On the other hand, programmes of this nature may give the employees a false sense of security and contribute towards interpreting of justifiable levels of exposure, on an incorrect basis. Biological monitoring and occupational medical screening include, as a rule, more well directed programmes which will probably be employed to a greater extent in the coming years. Finally, a set of American directives for criteria of utilization, particularly for screening in occupational medicine are discussed. It is maintained here, among other things, the necessity of an integrated analysis of biological monitoring, screening and control of exposure so that health surveillance can be of benefit for all the employees at a workplace and not only the individual worker. PMID- 2238193 TI - [Leber's hereditary optic atrophy. A hereditary disease caused by mitochondrial DNA mutation]. AB - Leber's hereditary optic neuropathy is a genetic disorder characterized by sudden bilateral loss of vision. It is transmitted exclusively through females (matroclinous inheritance) due to a mutation in mitochondrial DNA (mtDNA), most frequently a GC----AT substitution of base pair no. 11778 ('The Wallace mutation'). All children of homoplasmic female carriers inherit the disease gene. Penetrance is incomplete, but high in males. Genetic heterogeneity has been reported, as has heteroplasmy. The nature of the mutation and the degree of heteroplasmy have prognostic value, and genetic counselling as well as clinical evaluation should therefore include mtDNA analysis. Diagnostic mtDNA analysis is illustrated for three Danish patients, one of whom is without known affected relatives. All three were homoplasmic for the Wallace mutation. Neither prophylaxis nor therapy, by medication are possible as yet. Loss of vision may be prevented, or delayed, if at-risk individuals refrain from smoking and consumption of certain foodstuffs. PMID- 2238194 TI - [Variations in frequency of Cesarean sections in Denmark]. AB - An investigation is presented on the basis of the medical register of births concerning all primiparae who were delivered of a liveborn singleton infant in 1982 and 1986. On the basis of the section on complications in the notification of the births, we have made a subdivision into four "approximate indications". We find a variation in frequencies of Caesarean section from 9.7% (1982) to 17.1% (1986) between the various counties and an increase during the period investigated of 19%. 50% of the increase occurred in the group termed "other causes", 25% in the group of foetal distress and 25% in the group of dystocia. The group of breech presentations is, by and large, unchanged in Denmark as a whole but great differences are present between counties. This register investigation does not permit the possibility of deeper analysis of the reasons for the variations. PMID- 2238195 TI - [Prenatal diagnosis in the county of Viborg before and after decentralization of sample taking]. AB - On account of an increase in the frequency of amniotic fluid samples (AFS), the need for further decentralisation of sampling developed. Viborg Amt (Viborg County) was able to offer this service to all pregnant women in the county after 01.VIII.1985 who fulfil the indication for prenatal diagnosis (PD). Among 902 registered AFS divided over a period of two years before and two years after the decentralisation there was no significant deterioration of the service measured by the number of spontaneous abortions and unsuccessful AFS. The indications for prenatal diagnosis altered in such a way that the unofficial indication of anxiety rose significantly while the indication of maternal age greater than or equal to 35 years decreased. Furthermore, a positive correlation was registered between a reduction of distance from the pregnant woman to the centre of sampling and the percentage of referrals made by the local practitioner. The paper also shows that more pregnant women, referred for AFS on account of advanced age, accepted PD than was registered in an earlier research, but this pattern declined in the research period. PMID- 2238196 TI - [Information to women applying for sterilization]. AB - On the basis of a questionnaire investigation among the general practitioners in the County of Frederiksborg, the authors have compared the information given to women applying for sterilization with information in the available literature about the nature of the intervention, its sequelae and the risks involved. The authors found that under half of the practitioners gave informations about disturbances of menstruation, dyspareunia and altered sexual life. In the literature, it is stated that these occur in 10-60%, 3-11% and 4-48% of the women. Less than one third of the practitioners gave information about the risk of perforation of an organ or vessels, tearing of the ovarian tubes and postoperative pain. In the literature, it is stated that these occur in 0.1-2.5%, 0.28-9% and 24% of the women depending on the operative method used. The authors recommend revision of our knowledge on these subjects and alterations in the written information provided. PMID- 2238197 TI - [Hearing of the mentally retarded living at home]. AB - The present article was undertaken to illustrate the frequency of defective hearing in adult mentally retarded persons living in their homes in the Municipality of Copenhagen. The investigation concerns 115 persons, 57 men and 58 women with an average age of 38 years, range 20-79 years. At the time of the investigation, the persons examined constituted 26% of the total population of adult mentally retarded persons living at home in the Municipality of Copenhagen. The investigation revealed that 5% experienced problems in hearing in quiet surroundings while 15% had hearing problems with background noise. On the basis of pure tone audiometry, normal hearing was found in 60% (less than or equal to 20% dB HL) with frequency criterion including 4 kHz, while 67% (77/115) were found to have normal hearing without including 4 kHz in the frequency criterion. In other words, 40%/33% had defective hearing and were therefore outside the normal range. In order to assess the presence of defective hearing, the limit of greater than or equal to 25 dB HL in the ear with best hearing and the frequency criterion with or without 4 kHz, respectively, was established. On the basis of these criteria a reduction of hearing in the best ear of 30%/24% was found. the investigation revealed, in addition, that at least 17% should have been treated with hearing aids but only one of the persons examined had a hearing aid which was, however, not in use. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238198 TI - [Drug utilization in Hvalso. An attempt to change the attitude of the population and physicians to drug use]. AB - All of the prescriptions, a total of 1,876, issued by the five practitioners in Hvalso in four chosen weeks in 1987/88 were copied. The prescribed drugs, a total of 3,177, were calculated for the individual groups of drugs and corrected for the age distribution among the population as a whole and in the individual doctor's practice. The main results from the following groups of drugs are presented here: hypnotics, drugs for neurosis, antibiotics, drugs for cardiac and circulatory disease, drugs for asthma, contraceptive pills and female sex hormones. By and large, considerably more medicine was prescribed for women than for men. For example, twice as much medicine for insomnia was prescribed for women. This is enough for every fourth woman over the age for 70 years to receive a daily dose of hypnotics. Women appear to commence using hypnotics at the age of 40 years and men at 60 years. Marked differences were found in the patterns of prescription between the individual practitioners and thei is apparently greatest as regards prescriptions for men while the more liberal prescription of hypnotics to women was observed for all of the practitioners. Two groups of drugs were, however, prescribed mostly for men, viz, asthma medicine for all age groups and cardiac and circulatory medicine for persons greater than 60 years. Where all of the groups of drugs were concerned, comparisons were undertaken between the prescription habits of the individual practitioners. The results of this investigation are employed in local health work among the population, in study circle work among the practitioners and as basic ideas for the county drug committee activities. PMID- 2238199 TI - [Temporary pacemaker treatment in Denmark]. AB - The employment of temporary pacing (TP) in Denmark in 1986 is illustrated by means of a questionnaire investigation. Seventy-four out of 77 Danish hospitals with a medical-cardiological specialist returned usable replies. Facilities for temporary pacing were available in 39 (53%) of the hospitals. The method of pacing most extensively employed was the transvenous method which was used in 33 hospitals while external transcutaneous pacing by Zoll's method was available in 13 hospitals. In transvenous pacing, the subclavian vein was employed routinely in 24 hospitals while a cubital vein was used primarily in eight hospitals. More than 85% of the pacing catheters employed were of disposable type. Only one hospital always employed a permanent pacing lead which could be utilised if permanent pacing should be required. A total of 486 patients with or without acute myocardial infarction (AMI) were submitted to temporary pacing. Employment of temporary pacing in patients with AMI was 0-8.3% (average 3.7%). In general, it was found that hospitals with cardiac laboratory facilities showed the greatest temporary pacing activity. The indications for temporary pacing are assessed on the basis of two case reports. The greatest employment of temporary pacing was found in patients with AMI with third degree atrioventricular block and ventricular escape rhythm (anterior wall 74%, posterior wall 56%). Employment of temporary pacing was least in symptomfree patients with anterior wall AMI and bifascicular block (9%). PMID- 2238200 TI - [Reoperation for angina pectoris]. AB - During the 16-year period from 1974 to 1989, coronary bypass operations were carried out on 938 patients. During the same period, 48 patients (5.1%) were submitted to reoperation on account of recurrent angina pectoris. Patients with early recurrence had more frequently graft-occlusion than patients with late recurrence in whom the main cause was progression of the arteriosclerotic cardiac condition. The actual rethoractomy was carried out without serious complications. The perioperative frequency of complications and the mortality correspond to the frequencies at the first operation. Follow-up control of these patients was undertaken after an average of 34 months (8-100) after reoperation. The results after reoperation as regards freedom from symptoms are not quite as good as the results after the primary operation but approximately 2/3 of the patients will benefit from reoperation. PMID- 2238201 TI - [Unwanted pregnancy after removal of the IUD]. AB - Four cases of unwanted pregnancy occurring in the same cycle as removal of an IUD are presented. The duration of ovum transport from the Fallopian tube into the uterine cavity, survival of spermatozoa in the female genital tract and timing of ovulation, which may be delayed in women with IUDs are variables which influence the probability of pregnancy and should be taken into consideration when removing an IUD. Unless pregnancy is desired, it is recommended when possible not to remove an IUD after the ninth day of the menstrual cycle unless another contraceptive method has been initiated. PMID- 2238202 TI - [Allergy to insulin developed during exposure to human insulin]. AB - A case of allergy to human insulin is presented. The allergy developed during treatment with semisynthetic humanised insulin and was verified by a prick-test and RAST analysis. PMID- 2238203 TI - [Why are chronic pain patients given opioids via injections?]. PMID- 2238204 TI - [Gambling mania]. PMID- 2238205 TI - [Physical therapy and mask treatment of chronic bronchitis and chronic obstructive lung disease (COPD)]. AB - The literature concerning traditional chest physiotherapy (postural drainage, percussion, vibration, breathing exercises), treatments with masks (CPAP, IPPB, RMT, PEP, PEEP) and general physical training in the treatment of chronic bronchitis is reviewed. The mucociliary clearance is increased after postural drainage, cough, forced expiratory manoeuvres and general physical training, but the influence of this upon the course of the disease is unknown. Chest physiotherapy in the treatment of patients admitted on account of acute exacerbation of chronic bronchitis does not appear to help. The use of face masks in this population has only been subject to limited investigation, but results from controlled trials do not indicate any favourable effect. In contrast, general physical training seems to increase physical endurance and decrease dyspnoea. Specific rehabilitation programmes comprising psychological assistance, cessation of smoking and general physical training seem promising. PMID- 2238206 TI - [Testicular torsion in neonates. With special emphasis on bilateral cases]. AB - The literature concerning torsion of the testis in neonates is reviewed with special reference to bilateral cases. The incidence, pathogenesis, diagnosis, differential diagnoses and treatment are discussed. The importance of immediate surgical intervention is emphasized in order to avoid necrosis of spermatogenic tissue and subsequent infertility. PMID- 2238207 TI - [Urinary symptoms in elderly women in nursing homes. Frequency and social consequences of urinary incontinence in elderly women living in nursing homes]. AB - All 278 female residents of nursing homes in the County of Roskilde were assessed as regards the extent and severity of urinary incontinence and possible urinary infections. A total of 168 (58.5%) were incontinent. Culture of the urine was performed in 210 women and significant bacteriuria was demonstrated in 50%. Thirty-four out of the total of 287 women (12%) had indwelling catheters. In incontinent women without catheters, great quantities of urine were often voided involuntarily. Despite this, only few were subjectively inconvenienced or inhibited in their social activities. The investigation revealed a connection between urinary incontinence and reduced mobility while no connection was observed with current urinary infections, intake of medicaments and parity. It is emphasized that these results are based on findings in very old women living in nursing homes. PMID- 2238209 TI - [Medical services on an inspection ship in the north Atlantic]. AB - The Danish Naval Inspection Ships sail in the North Atlantic waters with a doctor on board. The object of this investigation was to illustrate the medical services on board and to elucidate the significance of various factors to predict seeking medical advice. During a period of three months, all of the medical services and certain basic factors were registered. The crew was interviewed about consumption of alcohol and tobacco, previous life at sea and family background. A total of 305 consultations were used by the crew of 72 men. This figure is five times the anticipated figure in general practice. Low rank and low age were predictors for frequent medical consultations. The diagnosis groups of traumata/injuries, dermatological conditions and disease in the nervous system or organs of sense were relatively overrepresented. A series of factors may possibly have influenced the pattern of seeking medical help so that this differs from general practice. It is concluded that the dangerous working environment and poor possibilities for good hygiene are important factors whereas the mental stress is of lesser significance. PMID- 2238208 TI - [Urinary incontinence in women aged 30-59 years. An epidemiological study]. AB - Among the female population of Aarhus Municipality, Denmark, 3,114 women were drawn at random and sent a postal questionnaire about the occurrence of urinary incontinence (UI) in adult life. The response rate was 85%. 26% of the respondents had experienced one or more episodes of UI in adult life. 14% had perceived UI as a social or hygienic problem cf. the UI definition of The International Continence Society. The mean 1987 period prevalence was observed to be 17% (ICS defined UI, 10%). UI incidence rose with increasing age, especially in age groups 25-29 and 45-49 years. By the age of 59, 30% had experienced UI (ICS defined UI, 18%). Pure stress UI and combined stress and urge UI were the most frequent clinical types. PMID- 2238210 TI - [Wound complications after suturing of Achilles tendon ruptures]. AB - During the period 1983-1988, 254 patients underwent simple end-to-end repair of closed ruptured Achilles tendons in our institution. During the same period, eight patients were treated with plastic repair on account of old ruptures, and 19 patients were treated conservatively on account of relative contraindication to open repair. The material of simple end-to-end repair is analyzed as regards factors which may be supposed to contributory to the rate of infection, wound healing and repeated rupture. The rate of major wound complication was low (2.4%) as was the rate of repeated rupture (1.6%). No single factor responsible for complications could be pointed out. However, compared to a high rate of deep infection in patients treated with plastic repair in our material and also in other studies, simple end-to-end suture is recommended in the treatment of rupture of the Achilles tendon when this is possible. PMID- 2238211 TI - [Frequency of recurrence after acute herniotomy]. AB - Ninety-one cases of emergency herniotomy are reviewed as regards the short- and long-term results. The review shows that immediate surgery does not involve any increased risk to the patient as regards mortality and recurrence rate. The frequencies of bowel resection and mortality are related to the duration of the history and the type of hernia. PMID- 2238212 TI - [Experience with Doppler echocardiography in infants with systolic murmur]. AB - In a one-year period, 33 infants with a systolic cardiac murmur were examined by Doppler-echocardiography. The clinical diagnosis based on ECG, X-ray and physical examination by a pediatrician or cardiologist was changed or established by Doppler-echocardiographic examination in 63% of the cases. In almost all cases, this meant changing of the strategy concerning further diagnostic evaluation and therapy. In eight (24%) of the infants no malformation was detected by Doppler echocardiography, and no further cardiological examinations were carried out. In eight (24%) infants a complex heart malformation was detected. Three of these infants had no clinical signs of heart disease except for the murmur. Because an early and accurate diagnosis is important in the management of infants with heart disease, we recommend that infants suspected of having congenital heart disease are examined by Doppler-echocardiography in a department with experience in this technique. PMID- 2238213 TI - [Proctoscopic versus histologic diagnosis of rectal polyps]. AB - On the basis of the endoscopic appearance, 71 rectal polyps were assessed as adenomata or non-neoplastic polyps, after which the endoscopic diagnosis was compared with the results of histological examination. The diagnosis based on macroscopic examination of the polyps proved correct in only 62% of the cases. It is concluded that the diagnosis of adenoma cannot be established solely on the proctoscopic appearance of a polyp and, as adenomata are premalignant, removal of all polyps found at proctoscopy is recommended. PMID- 2238214 TI - [Rupture of biceps tendon after injection of steroid]. AB - A case of distal rupture of the biceps tendon preceded by injection of steroid on account of lateral epicondylitis three and five months previously is presented. This complication is extremely rare although the treatment is extensively employed. It is recommended that steroid should not be employed as the first choice. In addition active measures should be employed to avoid recurrence. PMID- 2238215 TI - [AIDS and dementia]. AB - Two case histories are presented of patients with AIDS. In both cases, the initial symptom, apart from the generalized symptoms, was rapidly progressive dementia. The most important neurological symptoms in the AIDS dementia complex are reviewed and the CNS complications of AIDS are mentioned. In patients with atypical neurological clinical pictures, the diagnosis of AIDS should be considered. PMID- 2238217 TI - [The DANAMI study. A Danish multicenter comparative study of medical and invasive treatment in patients with ischemia after acute myocardial infarction]. PMID- 2238216 TI - [2 fatal cases of pneumococcal septicemia after bone marrow transplantation]. AB - Patients with bone-marrow transplants have an increased risk of developing fulminant pneumococcal infections for years after transplantation. In order to illustrate this, two cases of fetal pneumococcal septicaemia in patients with bone-marrow transplants are described. Self-medication with penicillin in case of fever is recommended. PMID- 2238218 TI - [General anesthesia without gas]. PMID- 2238219 TI - [Cholesterol anarchy?]. PMID- 2238220 TI - [Smoking among health personnel and smoking regulations in Danish hospitals]. PMID- 2238221 TI - [Knowledge and attitudes to the tobacco problem among Danish physicians, nurses and midwives in 1989]. AB - In an investigation including 2,233 Danish doctors, nurses and midwives between 72 and 96% replied that they found definite proof of connections between smoking and the diseases: cancer of the lung, cardiac infarction and chronic bronchitis. The highest percentages were found among doctors and, in all three instances, among nonsmokers. Approximately 2/3 of the persons questioned felt inconvenienced by other peoples' tobacco smoke. Even among health staff, there were, surprisingly enough, often problems between smokers and non-smokers. The majority of persons questioned considered that Danish hospitals and places of work for health staff should be free from smoke, so that none of the staff smoked at work. Half of the doctors and 3/4 of the nurses and midwives replied that they received insufficient teaching about the deleterious effects of tobacco smoking on health. All of the participants were unanimous that future campaigns against the tobacco problem in the population should be concentrated on prevention of recruitment of new smokers and increase of information about the deleterious effects of tobacco on health. As health staff constitute a very important group in the future campaigns against tobacco, we have obtained the impression from the questionnaire investigation that a thorough debate is necessary about how to solve the problem of tobacco smoking in Danish hospitals and other places of employment of health staff. PMID- 2238222 TI - [Smoking habits among Danish physicians, nurses and midwives in 1989]. AB - Health staff play a central role in distribution of knowledge about the injurious effects of tobacco by influencing the smoking habits of the population. The danish council on smoking and health has therefore chosen health staff as one of the first targets for its activities. One of these was conduct of a questionnaire investigation among a representative section of Danish doctors, nurses and midwives about smoking habits and attitudes to the tobacco problem. The random sample consisted of 2,997 persons, of whom 2,606 (87%) replied to the question about daily smoking habits. In all of the age groups, the frequency of smoking was considerably lower among health staff than in the population as a whole, primarily because many had stopped smoking. The frequency among men was 23% for doctors as compared with 50% in the normal population (age 20-69 years) and 15% for female doctors, 29-30% for nurses and midwives as compared with 46% in the normal population. The frequency of smoking among doctors has decreased considerably since 1980. Very few heavy smokers were found among health staff, particularly among doctors, and many male doctors smoked pipes (47% of the smokers). Even though health staff smoke less than the rest of the population, attention must still be focussed on this group on account of its function for establishing opinions in the health sector. PMID- 2238223 TI - [Selective screening for hypercholesterolemia. Results from a screening model in general practice]. AB - At present, it appears to be probable that both dietary changes and medicinal treatment can reduce the risk of development of coronary disease in middle-aged men with moderately to severely raised blood cholesterol values. Internationally, the limits for cholesterol intervention are considerably lower than in Denmark. Extensive cholesterol screening is, however, very expensive and the identified persons with high cholesterol values will frequently be found in sex and age groups where the beneficial effect of intervention is probably limited. A model for selective cholesterol screening in high risk groups in general practice is described here. In 20 general practices, all of the men aged 45-59 years belonging to the practice were invited to examination of cholesterol and blood pressure. Plasma cholesterol was measured by means of a Reflotron (results are available within three minutes) and the blood pressure and tobacco consumption were registered. After this, the patient's own general practitioner calculated with each of the persons the risk for development of myocardial infarction within the next ten years and intervention could be commenced immediately. 41% of those invited came for examination. Out of these, 29% had cholesterol values greater than or equal to 7.0 mmol/l (Danish limiting value), 44% greater than or equal to 6.5 mmol/l (limiting value in the remainder of Western Europe), and 5% greater than or equal to 9.0 mmol/l (severe hypercholesterolaemia) while only 18% had completely normal cholesterol less than 5.2 mmol/l. In every practice, two patients on an average were found with severe hypercholesterolaemia greater than or equal to 9.0 mmol/l. 28% of the participants had at least two of the three risk factors investigated. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238224 TI - [Formalized dietary advice in hypercholesterolemia. Results in 110 men diagnosed by selective screening in general practice]. AB - In connection with a screening investigation for high blood cholesterol in middle aged men in general practice in the Municipality of Copenhagen, all participants with cholesterol values greater than or equal to 7.5 mmol/l were given brief advice by their own general practitioner and were invited to come for fasting blood lipid tests approximately ten days later. In cases with continued cholesterol greater than or equal to 6.8 mmol/l, the participants together with wives or partners were invited to formalized dietary advice in small groups. Already before the formalized dietary advice, an average decrease in serum cholesterol of 10% was observed. This was attributed to biological variation, absence of fasting, the degree of error between the measuring methods and also a genuine decrease on the basis of the brief dietary advice by the general practitioner. On control after dietary advice, a further decrease in cholesterol of 15% was observed while low density lipoprotein cholesterol fell by 20% and triglycerides by 23%. These decreases must be considered to result mainly from the dietary advice. It is concluded that a single but professional session of dietary advice in small groups and with involvement of the wives or partners is an effective method of treatment in hypercholesterolaemia. If the decrease in cholesterol obtained can be maintained, the literature suggests that the risk of development of ischaemic heart disease during the subsequent 5-7 years is reduced by 20-30%. PMID- 2238225 TI - [Measurement of blood cholesterol, decentralized, using a Reflotron, or centralized in a laboratory. A comparison]. AB - In connection with an extensive screening programme for blood cholesterol, the cholesterol values in 105 participants were measured on a sample of capillary blood employing a Reflotron and, simultaneously, samples of venous blood were examined by conventional enzymatic analysis in a laboratory. Whereas the day-to day variation and the scatter involved were quite limited in the laboratory, the variation scatter between the two methods of measurement was 0.65 mmol/l. This figure was, however, no greater than that described between different laboratories in USA. Nevertheless, it is an important problem with the Reflotron method that even slight deviations from the recommended procedure of withdrawing blood involve a systematic risk for erroneously low cholesterol results. PMID- 2238226 TI - [Screening for cardiovascular risk factors in a large workplace]. AB - A screening investigation was carried out in a large industry in the Copenhagen region and 1,472 of the employees were offered examination of blood cholesterol and measurement of blood pressure. At this examination the employees completed a one-page questionnaire about other cardiovascular risk factors. 45% of those invited participated in the investigation, the poorest participation was among women and the greatest among the male officials. On account of the limited number of female employees, the majority of results were only calculated for men. Over 1/3 of these had hypercholesteremia (greater than or equal to 7.0 mmol/l) and nearly 1/3 had, simultaneously, at least two cardiovascular risk factors in addition to age and male sex. Extensive occupational investigations under the auspices of WHO have demonstrated that energetic intervention at the place of work aimed at the cardiovascular risk factors can reduce the risk of development of coronary heart disease and death within a six-year follow-up period. It is therefore emphasized that similar interventions are very necessary also in Denmark. PMID- 2238227 TI - [Intensive dietary advice for patients with severe hypercholesterolemia]. AB - Screening in general practice revealed a total of 124 patients (71 men and 53 women) with severe hypercholesterolaemia, defined as serum cholesterol levels over the 95th percentile for sex and age. The average serum cholesterol was 9.3 mmol/l with a maximal value of 15.5 mmol/l. On the basis of a dietary history for 48 hours and a dietetic interview, a dietician undertook a dietary analysis with the help of a computer programme (DANKOST) before and after dietary alterations for one and three months. The aims were normal body weight, cholesterol intake of under 200 mg/day, ratio between saturated and unsaturated fat between 1.0 and 1.8 and a roughage content of 26-30 g/day. A total of 61 patients completed the recommended dietary alterations. Alcohol intake was significantly higher in men and constituted more than 8% of the energy intake in 43 patients. Serum cholesterol was reduced by a total of 15.3%, triglyceride by nearly 20% while high density lipoprotein remained unchanged. The maximal decrease in serum cholesterol was 43%. In patients who adhered to the dietary changes, the average decrease was over 20%. Patients with hypertension and patients with serum cholesterol levels greater than or equal to 9 mmol/l showed greater decreases than the group as a whole. On the basis of the dietary interview, it did not prove possible to predict which patients would stick to the dietary restrictions. PMID- 2238228 TI - [Treatment of severe primary hypercholesterolemia with lovastatin (Mevacor). A new therapeutic principle]. AB - An open clinical trial comprising 59 outpatients with severe hypercholesterolemia (including 35 patients with familial hypercholesterolaemia) and considerable predisposition to ischaemic cardiac disease revealed a dosage-related pronounced effect of lovastatin on serum cholesterol and subfractions of this. After dietary regulation for a period of four months, a decrease in serum cholesterol of 11.7% was observed and after further treatment for six months with lovastatin with an average dose of 59 mg per 24 hours, the serum cholesterol decreased with a total of 45% of original value. Low density lipoprotein (LDL)-cholesterol decreased 44% and high density lipoprotein (HDL)-cholesterol increased by over 21%. Serum triglyceride fell by 20%. The serum-cholesterol/HDL-cholesterol ratio was reduced from 8.8 to 4.9. Only slight and transient subjective side-effects were observed and none of the patients dropped out of the trial for this reason. One patient with recognized ischaemic heart disease died from myocardial infarction. A tendency towards increasing liver parameters and creatin kinase was observed in the group as a whole but was not significant. PMID- 2238229 TI - [Smoking regulations in Danish hospitals]. AB - An investigation undertaken by the Danish Council on Smoking and Health in July 1989 concerning smoking rules in Danish hospitals reveals that still fewer hospitals or hospital departments permit entirely free smoking. Conditions are, however, far from satisfactory everywhere. Smoking is permitted in no less than 28% of hospital wards in Denmark. In 82% of hospitals or departments, smokers and nonsmokers are admitted to the same sickrooms. In one fifth of the Danish hospitals, non-smokers risk being admitted to sickrooms where smoking is permitted. This is not acceptable. In 2% of hospitals or hospital departments, there are no restrictions about smoking for the caring staff. In 27% of hospitals or hospital departments, there are no smoking restrictions for the administrative staff. Only 2% of hospitals or hospital departments have complete prohibition of smoking. Many hospitals or hospital departments have no restrictions concerning common areas. This is true for 26% of the waiting rooms, 20% of the elevators, 30% of the passages and 46% of the lavatories. A total of 2% of hospitals or hospital departments have no smoking restrictions for visitors while 14% have complete prohibition of smoking for visitors. The goal of smokeless working environments for all health staff is recommended. PMID- 2238230 TI - [Acceptance of HIV antibody testing among pregnant women]. AB - During the period April 17-July 14, 1989, 820 pregnant women were offered HIV antibody testing at the antenatal clinic, Aarhus Municipality Hospital. Seven hundred and seventy-nine (95%) agreed to complete a questionnaire concerning, among other things, previous HIV-antibody testing. 20% of the participants had been tested previously, half of them because they were blood donors. More than 3% had been tested because of self-perceived risk behaviour or a risk environment. In three women, the previous test had shown HIV-antibodies to be present, and three further women refused to report the test result. 81% of the women consented to be tested. Acceptance declined during the project period. Those who had not been tested previously consented more frequently than those who had. Students were less willing to consent than others. Nineteen out of 20 women (2.6%), who considered themselves at high risk, accepted the offer to be tested. Thirty-eight (5%) of the 150 women who declined to be tested, would have accepted if their general practitioner had suggested it. None of the women tested at present were found to be HIV-antibody positive. When the project was terminated, a total of 87% of the women had been HIV-antibody tested previously or at present. We suggest routine HIV surveillance of pregnant women by use of voluntary HIV antibody testing in combination with anonymous testing (AUT technique) in case the women does not want to know the test result. PMID- 2238231 TI - [Biopsy of chorionic villi]. PMID- 2238232 TI - [Metformin-associated lactic acidosis]. PMID- 2238233 TI - [Short muscles in children and adolescents in an orthopedic practice]. PMID- 2238234 TI - [Gastroesophageal reflux and esophagitis]. PMID- 2238235 TI - [Treatment of postoperative pain]. AB - Intensive research during recent years concerning treatment of postoperative pain has demonstrated that the majority of operation patients can be rendered free from pain but that this is far from being the case in clinical practice. This article reviews the physiological mechanisms of acute pain and the methods available for treatment of pain related to acute physiology of pain. Postoperative treatment of pain should be aggressive with the object of preventing pain and normalizing the vital functions with the object of reducing the perioperative morbidity and mortality. A series of recommendations are given for treatment of pain after surgical intervention. PMID- 2238236 TI - [Radiographic diagnosis of abdominal manifestations of AIDS]. AB - Abdominal complications as intercurrent infections and malignancies in AIDS patients are one of the principal sources of morbidity and mortality in this disease. Air-contrast barium radiography of the gastrointestinal tract and computed tomography or sonography of the abdomen is of great clinical value in the evaluation of visceral and nodal lesions in AIDS. The diagnosis is impeded by the coexistence of several diseases in many of the patients and the nonspecificity of the radiographic findings. PMID- 2238237 TI - [Risk factors in home accidents among preschool children]. AB - The present investigation is part of an investigation concerning preschool children's accidents at home. A total of 3,011 homes with preschool children were examined with the object of reducing the number of accidents involving preschool children. Selected risk factors were registered (falls, burns, poisoning) responsible for accidents to preschool children in their homes and this information was compared with information about the type of housing, district and the social status. The investigation revealed that 30% of the homes had "dangerous" windows, 30% had taps which could be swung out over free floor space and 42% did not have special electric safety main switches. Articles for cleaning, medicine and poisons were only stored in locked cupboards in 2.5 and 8% of the homes, respectively. These circumstances were more common in flats than in one-family homes. No significant differences were found between the physical risk factors chosen in the present investigation between the individual social status groups. Prevention of children's accidents in the home consists of increased information to families with children, to architects and manufacturers and increased attention to safety in the home by legislation and guidelines. PMID- 2238238 TI - [The cardiovascular risk profile in the Glostrup region, Monica screening II, 1986/87]. AB - Information about risk factors and cardiovascular disease was collected from 30, 40, 50, and 60 year old representatives of the suburban Danish population (n = 1,504). Reference values for systolic and diastolic blood pressure and total serum-cholesterol are given. A comprehensive risk profile is discussed on the basis of selected risk factors: arterial hypertension, total serum-cholesterol greater than 7.5 mmol/l, smoking of ten cigarettes or more per day, intake of five alcoholic drinks or more per day, lack of physical exercise, and body mass index greater than 25 kg/m2. PMID- 2238239 TI - [Acute admissions to the Psychiatric Children's Hospital, Risskov, during 1 January 1982-31 December 1987. A retrospective descriptive study]. AB - During the period concerned, 50 children were admitted as emergencies to the Psychiatric Children's Hospital. These were compared with 90 children over the age of nine years who were admitted in the ordinary manner during the same period. The children admitted as emergencies were aged ten years or more, they were older than the control group and the sex distribution was more uniform. The emergency admissions were, as a rule, instigated by the parents. Half of the families involved had had contact with the Children's Psychiatric Hospital previously. The majority of the children in the control group were referred by school psychologists. The three most important reasons for emergency admission were psychotic symptoms, threats of suicide or attempted suicide and behavioural disorders. Nearly half of the children admitted as emergencies were hospitalized for less than three months and nearly one third were hospitalized for less than one month. Almost all of the children admitted as emergencies and all of the children in the control group had had contact with the social supportive agencies prior to admission. The recommendations on discharge did not differ essentially in the two groups. PMID- 2238240 TI - [The Swanson silicone implant for wrists in rheumatoid arthritis]. AB - The Swanson silastic implant was employed in 16 wrists in 13 patients who were followed up for a median of 59 months. At follow up examination, pain had decreased in ten wrists while three remained unchanged. Ten patients were satisfied with the total result. Only few complications occurred. Prosthetic fracture occurred in two wrists (14%). The authors consider that the Swanson silastic wrists implant can produce favourable results in patients with rheumatoid arthritis with moderate to severe radiological destruction. PMID- 2238241 TI - [Genital prolapse and urinary incontinence. A clinical assessment of patients with prolapse with particular emphasis on surgical methods and their long-term effects]. AB - A review based on a follow up of 215 patients who had been treated operatively for genital prolapse and urinary incontinence after observation for 5-10 year is presented. The operation regime was predominantly conventional and the various vaginal methods involved 182 patients (80%). The Kelly-Kennedy plastic operation (K-K-pl) was employed for stress incontinence and slighter cases of prolapse. In more severe degrees of both of these conditions, K-K-pl was combined with the Manchester operation. The operative method of election in this department for marked cases of utero-vaginal descent was the Manchester operation supplemented by colpo-perineal plastic. The most advanced cases of prolapse were treated either with the Moschowitz operation or colpocleisis. This investigation revealed that the late results of the individual methods at primary operative treatment of both prolapse and incontinence showed the same high results of treatment with satisfactory results in 75-100%. On the other hand, the results of secondary operation showed great variation, depending upon the method, with satisfactory results from 25-85%. PMID- 2238242 TI - [Accidents with home-made metal-tube fireworks]. AB - At the turn of the year 1988/89, injuries caused by home-made fireworks were treated in the orthopaedic-surgical casualty department. Four accidents are described. Construction and use of home-made fireworks are warned against. PMID- 2238243 TI - [Evaluation of the catalase reaction as a sign of pus in feces]. PMID- 2238244 TI - [Hospitals and disaster planning--once more]. PMID- 2238245 TI - Ultrasonic velocity hydration numbers of polyamines. AB - Ultrasonic velocity hydration numbers of diamines, triamines and tetraamines and hydrochlorides of these amines were determined by measuring the maximum velocity of ultrasound in aqueous-ethanolic solutions. The results are interpreted on the basis of the hydrogen-bonded framework model of the water structure. PMID- 2238246 TI - Non-contact acoustic method for the simultaneous measurement of thickness and acoustic properties of biological tissues. AB - The frequency dependence of the magnitude and phase shift of reflected waves from a thin tissue specimen has been found to yield characteristic patterns as a function of the specimen thickness. By analysis of those characteristic patterns, the specimen thickness can be determined so that the attenuation constant and the sound speed can be obtained by a non-contact procedure. The method is demonstrated in the frequency range 100 MHz to 200 MHz, using a scanning acoustic microscope and approximately 10 microns thick myocardial tissue samples of human origin, one paraffin embedded. PMID- 2238247 TI - Some of the factors involved in the Sarvazyan method for recording ultrasound field distributions with special reference to the application of ultrasound in physiotherapy. AB - The mapping of ultrasound fields using the dye paper method is described. The mode of action by which the dye concentration is increased has been investigated. Microbubbles on the paper surface and microstreaming of dye solution seem to be essential features of the mapping method. The streaming is thought to inhibit the formation of a dye depletion layer near the paper to an extent dependent on local sound intensity A linear relation between streaming velocity and intensity is derived. PMID- 2238248 TI - Microbial content of aerosols produced from suspensions exposed to megahertz frequency ultrasound. AB - A piezo-electric bowl transducer was used to generate aerosols by focusing ultrasound in the frequency range 1-7 MHz at a liquid/air interface. Atomization at the liquid surface and the production of a fountain contributed to aerosol formation. When the liquid consisted of suspensions of representatives from the viral, bacterial, and yeast groups of micro-organisms (covering a 0.2-11.5 microns size range) living organisms were isolated from the aerosols at all frequencies. The fountains were implicated as a major source of air-borne micro organisms because significant numbers of isolates were obtained in the presence of fountains but in the absence of obvious atomization, and theoretical predictions make the sizes of droplets arising from atomization at the higher frequencies too small to have carried some of the larger organisms. PMID- 2238250 TI - Observation of cesarean section scar by transvaginal ultrasonography. AB - Transvaginal ultrasonography, with its higher frequency and proximity to the pelvic structures has offered us a powerful tool for observing the uterine scar of a previous Cesarean section. We have examined 87 previous Cesarean section scars by transvaginal ultrasonography. Forty cases (group A) were in the third trimester. Fifty-two percent of this group showed normal patterns. In the remaining cases, thickening of the previous incision site was the most common finding. Also, thinning, ballooning and wedge defect were noted. Forty-seven cases (group B) were examined within 3 months (group B1) or after 3 months of Cesarean section (group B2). Similarly half of them showed normal patterns. In the remaining cases, wedge defect was the most common finding. The others were outward or inward protrusions, hematoma formation and inward retraction. An evaluation of the previous section scar, preferably by high resolution transvaginal ultrasonography is highly recommended in considering a trial of labor after previous Cesarean deliveries. PMID- 2238249 TI - The assessment of abnormal pelvic blood flow by transvaginal color and pulsed Doppler. AB - Transvaginal color Doppler was used to analyze a group of 19 healthy, 48 infertile and 8 postmenopausal women; 67 patients with uterine and 151 patients with adnexal masses, and 19 patients with a suspected ectopic pregnancy. The ultrasonographer had not been informed of other clinical findings and indications for operative treatment. A 5 MHz transvaginal color Doppler probe was used to visualize the pelvic anatomy and blood flow. Each arterial blood flow velocity was classified into either of two types. In the normal flow pattern, the diastolic flow component was absent or small and the value of resistance index (RI) was greater than 0.50. In the abnormal flow pattern, a large diastolic flow component was evident and the value of RI was less than 0.50. Transvaginal color and pulsed Doppler studies in confirmed malignant uterine masses had moderate accuracy (90.2%), with a sensitivity (55.6%) and specificity (100%); and in confirmed malignant adnexal masses high accuracy (100%), sensitivity (100%) and specificity (100%). Comparison of blood flow characteristics within benign and malignant tumor tissue revealed less impedance and higher velocity in cases of malignancy. Blood flow studies in both uterine arterias have not shown clinically important values. This method can be also used in the diagnosis of ectopic pregnancy. PMID- 2238251 TI - Doppler waveform pulsatility index and resistance, pressure and flow in the umbilical placental circulation: an investigation using a mathematical model. AB - A mathematical model of the umbilical placental circulation was used to examine the effect of different physiological variables on the pulsatility index (PI) of the umbilical artery Doppler waveform. The variables include the umbilical and placental resistances, the volume flow rate and the pressure. In the model the branching structure of the placental villous tree is considered in detail, while each arterial branch is itself represented simply using a resistor and a capacitor. Placental vascular disease is modelled as obliteration of a fraction of the terminal branches of the tree. The model umbilical artery PI depends on the ratio of the placental resistance to the umbilical artery resistance. The PI increases with vascular disease, but the rate of increase is not uniform. Initially, the placental resistance and the PI increase very slowly with vessel obliteration. Once the level of vessel obliteration has reached a large enough value--typically between 60% and 90% obliteration--the PI begins to rise sharply. A larger placental vascular bed can accommodate a greater level of vessel obliteration before this rapid PI rise begins. The umbilical artery PI also depends on the pulsatility of the input (aortic bifurcation) pressure waveform, but blood pressure variations in the physically attainable range cannot account for the very high PI values associated with fetal compromise. Physically attainable pressure waveform changes would, however, enable the fetus with substantial placental vascular disease to maintain umbilical volume flow rate, and at the same time exhibit a raised umbilical artery PI value. PMID- 2238252 TI - Biological effects of shock waves: effect of shock waves on the liver and gallbladder wall of dogs--administration rate dependence. AB - The effect of extracoporeal shock waves on the liver and the gallbladder wall was compared in two groups of dogs exposed to 1500 shock waves generated in an electrohydraulic lithotripter with 15 kV and 80 nF. The waves were focused on the gallbladder wall. In the experimental group, a shock wave burst of 10 consecutive waves with an interval of 10 ms between the waves was administered each second; in the control group, single shocks were released each second. The day following shock wave exposure, the dogs were anaesthetized, killed and then dissected. In the liver, subcapsular and intraparenchymal focal haemorrhages occurred in the high pressure field and venous thrombi in portal veins. There was a nonsignificant trend towards an increased number of venous thrombi after burst application. The gallbladder wall was haemorrhagic and oedematous, the mucosa was ulcerated in the focal area; blood clots were found in nearly all gallbladders. No differences were detected between the groups. The free plasma haemoglobin was only increased after fast shock wave administration. Increased haemolysis and the trend towards an increased number of thrombi favour cavitation as a mechanism of shock wave damage. The similar extent of tissue damage suggests that shock wave bursts can be applied for gallstone destruction in humans if the major liver vessels are kept out of the high pressure field. PMID- 2238253 TI - Biological effects of shock waves: cavitation by shock waves in piglet liver. AB - Shock waves are known to generate cavitation in vitro. In vivo, extracorporeal shock waves may cause haemorrhages in tissues. Two types of changes were detected by conventional, real-time B-scan ultrasound when shock waves were administered to 5 piglet livers in vivo: transient changes consisting of bright signals in intrahepatic branches of the portal vein and tributaries of the hepatic vein, presumed to originate from gas bubbles, and stationary changes consisting of brightening of the area along the long axis of the high pressure field, presumed to indicate an increased number of gas-filled bubbles in this area. Transient changes appeared from the start of shock wave administration; bright signals were seen in liver vessels for several hundred microseconds before they were flushed away with the blood flow. Stationary changes appeared later, increased in intensity over several hundred shock waves and persisted for minutes after cessation of shock wave administration. Both types of signals were interpreted as direct evidence that lithotripter shock waves generated cavitation in vivo. Similar signals were received in the partly degassed water of the lithotripter tub. At autopsy of the piglets, focal intralobular haemorrhages and thrombi of portal veins were detected in the shock wave path. The occurrence of cavitation and tissue damage in the same gross area suggests that cavitation might be involved in the generation of tissue damage by shock waves. PMID- 2238254 TI - A novel method to control P+/P- ratio of the shock wave pulses used in the extracorporeal piezoelectric lithotripsy (EPL). AB - There is growing evidence that acoustic cavitation plays an important role in stone fragmentation during extracorporeal shock wave lithotripsy (ESL) treatment. In addition, side effects of the treatment, such as the hemorrhage and destruction of the tissue in the vicinity of the stone are also ascribed to cavitation phenomenon. Since cavitation is associated with the maximum negative pressure in the shock pulse, it would thus appear that possibility of controlling this pressure would be desirable in ESL applications. This paper describes a novel technique developed to control the ratio of compressional peak (P+) to rarefactional peak pressure (P-) of the shock wave for use in lithotripsy treatment. The procedure is based on the finite amplitude wave generation by focused piezoelectric transducers and subsequent interaction of the shocked waves in the common focal region. The highly asymmetrical shock wave is produced in the focal region by providing an appropriate time delay to each of the high voltage electrical excitation signals which drive the transducers. The degree of relative reduction of negative halfcycles and the corresponding positive halfcycles amplification increases with the number of the acoustic sources used. The practical implementation of the shock wave generator was obtained by using 5 cm diameter, focused 1 MHz transmitter, and additional transducers of identical construction having frequencies corresponding to the harmonics and subharmonics of the 1 MHz frequency. The importance of the results for the future development of lithotripters, and stone treatment efficiency is pointed out. PMID- 2238255 TI - Temperature elevation generated by a focused Gaussian beam of ultrasound. AB - The steady state temperature elevation generated by a focused Gaussian beam, including the effect of perfusion, has been calculated along the beam axis. The medium is assumed to be a homogeneous absorbing one. The results indicate: (1) The temperature rise is an increasing function of the intensity gain of the focusing transducer, but never seems to exceed twice that at the interface of the transducer and the medium generated by its unfocused counterpart; and (2) The temperature rise at the interface of the transducer and the medium is not affected significantly by focusing. PMID- 2238256 TI - A triangulation method for the quantitative measurement of arterial blood velocity magnitude and direction in humans. AB - A triangulation method has been applied to a duplex ultrasound scanner to quantify blood flow velocities in two dimensions. A position locating system (PLS) connected to the scanhead locates the sample volume (SV) in 3-D space to a precision of 1 mm. The PLS is used to obtain flow velocity data from two independent lines of sight in the human femoral artery. Data are gathered from anatomic sites of interest along one line of sight. Later the computer directs the SV to interrogate the same points in space from a second line of sight. Water tank studies using both constant velocity and pulsatile string targets were used to validate the method. Velocity magnitudes could be calculated to within 5% error for Doppler angles below 75 degrees for various string depths and speeds; the error in Doppler angle calculation was usually less than 3 degrees. Results from the superficial femoral artery show flow velocity vectors are nearly parallel to the vessel walls. Peak systolic velocity magnitudes range from 63-66 cm/s in three presumed normal individuals. Following the validation studies addressed in this paper, this triangulation approach is intended in future work to document the complex nonaxial character of blood flow that occurs normally at branch points and in regions of intraluminal disease. PMID- 2238258 TI - Source of double Doppler shift in blood flow. PMID- 2238257 TI - On the behavior of instantaneous frequency estimators implemented on Doppler flow imagers. AB - Analytical and experimental results have been used to examine the behavior of the "autocorrelator" or instantaneous frequency detector (IFD) applied to color-coded Doppler flow mapping. Two effects were studied. The first was the influence of noise, as modified by a stationary echo canceler, on the Doppler frequency detector. Our theoretical considerations predict that uncorrelated input noise signals become partially correlated after cancellation, and bias the response to flow signals. This effect was confirmed by experiment. The canceler introduces a constant negative bias into the denominator of the algorithm implemented by the estimator, thus changing the indicated frequency. The second phenomenon, examined through processing computer simulated Doppler signals added to real noise, is related to the possible ambiguity, called aliasing, of measurements of the mean frequency for wide-band Doppler spectra. We show that aliasing cannot be observed with these spectra unless the signal is first processed by a canceler. Thus, regions of apparent reversed flow direction on two-dimensional flow images of turbulence must usually be due to real reversal of the flow direction. PMID- 2238259 TI - Calculation of Vmax incorporating dynamic range and attenuation. PMID- 2238260 TI - Doppler angle error due to refraction. PMID- 2238261 TI - Doppler or doppler? PMID- 2238262 TI - Doppler color flow in echocardiography: analytical and in-vitro investigations of the quantitative relationship between orifice flow and color jet dimensions. AB - The goal of this investigation was to explore the relationship between orifice flow rate and the dimensions of the resulting color jet. Equations were derived which describe flow rate as a function of the color jet dimensions, instrument characteristics, and a coefficient which represents the unknown velocity profile across the jet. Experiments in which fluid was injected at a variety of flow rates via an assortment of orifice sizes into a compliant, axisymmetric chamber were performed for comparison with the analytical results. During each injection, orifice flow rate and color jet dimensions were recorded. The experimental results were closely predicted (r = 0.97) by an equation which expresses flow rate as a function of the ratio of the color jet area and color jet length, and with a coefficient which approximates that of a parabolic velocity profile. PMID- 2238263 TI - Doppler ultrasound color flow imaging in the study of breast cancer: preliminary findings. AB - A prospective study of the Doppler color flow features of 55 proved breast cancers was performed. On a three-level scale of low to marked vascularity, visual assessment of the color flow images classified 82% of the cancers as moderately or markedly vascular (minimal: 14%, moderate: 29%, marked: 53%). Four percent of the cancers had no detectable flow. In 29 women, a volume of tissue comparable to the cancer was scanned in the contralateral normal breast. Sixty nine percent of the normal breasts had moderate or marked vascularity (minimal: 28%, moderate: 41%, marked: 28%), and 3% were avascular. There was poor distinction between normal tissues and cancer which suggests that more sensitive Doppler methods than were employed in this study may be needed in order to detect the small vessel flow reported to be rather specific for malignancy. The high, 82%, detection rate of tumor vessels in this study suggests the potential use of color flow Doppler for directing more specific but lengthy Doppler procedures. PMID- 2238264 TI - Quantitative tissue motion analysis of digitized M-mode images: gestational differences of fetal lung. AB - Quantitative analysis of transmitted cardiac motion in fetal lung is evaluated by applying correlation techniques to digitized M-mode images in 21 patients, subdivided into two subgroups by gestational age: (I) 25-30 weeks (11 patients), and (II) greater than or equal to 35 weeks (10 patients). The corresponding numbers of M-mode images analyzed for each group are 23 and 18, respectively. This partition is expected to reflect functionally "immature" and "mature" lungs. The estimated maximum mean radial deformation per unit epicardial excursion, (r), is calculated from the two-time, spatially averaged correlation function obtained between diastolic and systolic M-mode lines. The collective results for each subgroup are (r) I = 0.79 +/- 0.11 (sem) and (r) II = 0.62 +/- 0.13 (sem). The analysis presented, albeit in a limited population, is indicative of a trend in accordance with qualitative observations of Birnholz and Farrell (1985). M-mode analysis, as indicated by Adler et al. (1989) is a potentially useful technique to quantify such tissue motion. PMID- 2238265 TI - The use of a Diasonics DRF400 duplex ultrasound scanner to measure volume flow in arterio-venous fistulae in patients undergoing haemodialysis: an analysis of measurement uncertainties. AB - A pilot study to measure volume flow in arterio-venous fistulae in patients undergoing haemodialysis was undertaken to determine the accuracy and precision of values obtained using a modern duplex ultrasound scanner. A Diasonics DRF400 duplex ultrasound scanner was used with a small parts 10 MHz mechanical sector probe incorporating a 4.5 MHz Doppler transducer. Volume flow was measured in the brachial artery of 13 patients with surgically created arterio-venous fistulae in the distal circulation. Volume flow was also measured using a flow phantom in which the true volume flow was known. An analysis of the measurements made by the duplex scanner was performed to determine the sources of random and systematic uncertainty. Repeatability was improved with the probe clamped in position over the brachial artery giving a coefficient of variation in repeated measurements of volume flow in a patient of +/- 12%. Measured flows ranged from 884-3088 mL min 1. Comparison with measurements on the flow phantom showed these values from patients to be overestimated by 200-600 mL min-1. The values from the phantom should therefore be used to calibrate patient measurements. Analysis of uncertainties showed that precision was limited by random uncertainties in the measurement of vessel diameter and Doppler angle. PMID- 2238266 TI - Effects of lithotripter fields on development of chick embryos. AB - Chick embryos at 72 h incubation were subjected to three double shock waves from a Wolf Model 2137.50 Electrohydraulic Lithotripter. The pressure amplitude at the embryo was adjusted by variation of the distance from the source to the embryo. After a total of 120 h of incubation, they were assessed for developmental abnormalities. Early deaths, delayed deaths and malformations were all significantly increased at pressures of 10 MPa with suggestions of possible effects at lower pressure levels. PMID- 2238267 TI - Biological effects of shock waves: cell disruption, viability, and proliferation of L1210 cells exposed to shock waves in vitro. AB - L1210 cells were exposed in suspension to shock waves generated with a Dornier XL1 lithotripter. After 1000 discharges at 25 kV, the number of nondisrupted cells was 15% and the number of trypan blue excluding cells was 7% as compared to 100% in sham treated controls; the shock-wave effect was more prominent at higher voltages and less prominent at higher discharge numbers when compared at similar electrical input energies. Overall proliferation of cells which were trypan blue negative after exposure exceeded 70% of the proliferation of sham treated controls, except after 1000 shocks at 25 kV, where proliferation was reduced to 42%. The latter reduction in proliferation was found to be due to a reduced growth for 24 h after exposure, with a return to normal proliferation during the following days. Limiting dilution analysis revealed that the reduced growth was mainly due to a transitory increase of the doubling time and not to a reduction of the number of proliferating cells. Cell disruption by shock waves was completely inhibited by exposing the cells at an elevated pressure of 101 atmospheres, pointing to the possible involvement of cavitation in the shock wave effect. PMID- 2238268 TI - Influence of the shock wave application mode on the growth of A-Mel 3 and SSK2 tumors in vivo. AB - We examined the influence of different shock wave application modes with a Dornier XL1 electrohydraulic lithotripter on the growth of A-Mel 3 and SSK2 tumors implanted under the dorsal skin of hamsters or mice. In a basic protocol, 500 shock waves a day on 4 consecutive days were administered at a discharge rate of 100 waves per minute and focused to the tumor center. This did not affect A Mel 3 growth. A similar result was obtained with the basic protocol modified to 1000 shock waves a day and a wave application rate of 100 shock waves per second. Growth of A-Mel 3 and SSK2 tumors was significantly delayed, when the basic protocol was used, but the 500 shock waves a day were distributed over four points at the tumor edges and the tumor center. With the same shock wave protocol, lowering the water level over the tumor from 10 cm to 1 cm induced temporary regressions of SSK2 tumors. This was not due to the higher energy applied to the tumor, since twice the number of shock waves (1000 a day instead of 500 a day) was applied at a high water level and did not induce regressions. Four consecutive treatments with intervals between treatments shortened to 3 h and an additional treatment 12 h later at a low water level completely controlled tumor growth in 8 out of 12 SSK2 tumors for more than 150 days. The result showed that addition of a reflected wave from the water surface was most important for the shock wave effect, and suggested that shock wave devices generating similar wave forms should be applied for tumor therapy. PMID- 2238269 TI - A simulation of transit time effects in Doppler ultrasound signals. AB - A signal model is proposed which can be used to study frequency extraction techniques for Doppler ultrasound. The signal is based on the physics of the Doppler process and depends on a sliding window used to average a set of independent Gaussian random numbers. This window is related to the shape of the sample volume for the Doppler pulse and depends on the Doppler angle. Simulation results compare favorably with results from flow experiments in terms of the variance of the estimated Doppler shift, the shape of the power spectra and the behavior of the signals with respect to Burg autoregressive power spectra. A potential use of the signal in the study of spectral analysis techniques is presented. PMID- 2238270 TI - Bioeffects of diagnostic ultrasound on auditory function in the neonatal lamb. PMID- 2238271 TI - Shock wave lithotripsy produces large cavitation bubbles. PMID- 2238272 TI - [The self-treatment of the hemophiliac at home: "AIDS has come to jeopardize the experiences of these remaining years"]. PMID- 2238273 TI - [Osteoporosis: long-term prevention and future treatment. Interview by Robert Henry]. PMID- 2238274 TI - [Periodic medical examination, update 1989: 4. Electronic surveillance of the fetus during labor and prevention of herpes in newborn infants. The Canadian Study Group on Periodic Medical Examination]. PMID- 2238276 TI - [Cholesterol. The more the story advances, the more complicated it becomes. Interview by Robert Henry]. PMID- 2238275 TI - [Acute non-calculus cholecystitis. The Sherbrooke University Hospital Center experience 1969-88]. AB - This paper presents a survey of the experience gathered in the field of acute cholecystitis at the Sherbrooke University Hospital from 1969 to 1988. Diagnosis of acute cholecystitis in the absence of stone (according to histopathological criteria) was made in 26 cases. The relative number of such cases increased over the last 10 years of the study. Risk factors together with clinical and paraclinical data have been analyzed. Sonography is the diagnostic test of choice. Gall-bladder scanning is a useful adjuvant in cases of doubtful or negative sonography. Gangrene and/or perforation of the gall-bladder was reported in 57.7% of patients. Cholecystectomy was selectively performed in 23 of 24 cases when diagnosis was established in vivo. Cholecystectomy and percutaneous drainage are discussed. PMID- 2238277 TI - [Clinical case. Apropos of a case of precipitated polyuria in a hospital setting]. PMID- 2238278 TI - [1990 classification criteria of fibromyalgia from the American College of Rheumatology. Report of the Multicenter Criteria Committee]. PMID- 2238279 TI - [A 29-year-old patient consults for an abnormal ECG]. PMID- 2238280 TI - [Otitis: multiple problems of diagnosis and therapy. Antibiotics do not themselves alone control therapeutic efficacy. Interview by Robert Henry]. PMID- 2238281 TI - [Hypertension and the sympathetic nervous system: research to pursue. Interview by Robert Henry]. PMID- 2238282 TI - Transurethral prolapse of a simple ureterocele in a boy: case report. AB - Although simple ureteroceles are commonly encountered on urography, transurethal prolapse of the ureterocele in a male is an exceedingly rare complication. A fourth such case, with graphic, potentially confusing ultrasound and urographic findings, is presented and discussed. PMID- 2238283 TI - Ultrasound findings in diffuse granulomatous cystitis in chronic granulomatous disease of childhood. AB - Chronic granulomatous disease (CGD) is a genetically inherited disease of childhood, which is characterized by repeated bacterial and/or fungal infections. The genitourinary tract is rarely involved. We report a case of CGD with involvement of the urinary bladder. Pertinent clinical and sonographic findings of this disease are described. PMID- 2238284 TI - Hysterographic demonstration of multiple endometrial polyps: case report. AB - Endometrial polyps vary in size, shape, location, histology, and number. An unusual example of multiple endometrial polyps is reported. PMID- 2238285 TI - Bilateral fallopian tubal polyps: radiologic and pathologic correlation. AB - A case of bilateral fallopian tube filling defects found on hysterosalpingography performed on a patient for infertility work-up is presented. Repeat hysterosalpingography performed 4 years later showed no change. Microsurgical resection revealed the defects to be fallopian tubal polyps of endometrial origin. PMID- 2238286 TI - MR evaluation of renal space-occupying lesions: diagnostic criteria. AB - In order to assess the ability of magnetic resonance (MR) imaging to distinguish simple renal cysts from renal tumors, images from 53 patients with 74 lesions were reviewed. MR image characteristics, including signal strength and homogeneity for each lesion, were evaluated and compared with the final diagnoses. There were 53 cysts and 21 tumors. For 56 lesions (76%), MR allowed accurate diagnosis; on T1-weighted images, homogeneous low-intensity lesions were always cysts and inhomogeneous medium- or high-intensity lesions were always tumors. The remaining 18 lesions (24%) could not be distinguished, and T2 weighted images failed to improve differential diagnostic ability. In our experience, MR imaging allows differentiation of renal cysts and tumors less frequently than does computed tomography (CT) or ultrasound (US). MR criteria for simple renal cysts and tumors are offered, with the understanding that modification may be necessary as experience with these lesions increases. PMID- 2238287 TI - Unusual manifestations of renal artery aneurysms. AB - Two unusual cases of renal artery aneurysm are presented. The first, a 10.4-cm aneurysm, the largest yet reported, manifested as an abdominal mass in an otherwise asymptomatic patient. The second was associated with renovascular hypertension in a 6-month-old infant, the youngest patient yet reported. PMID- 2238288 TI - Embolization of iatrogenic renal hemorrhage following percutaneous nephrostomy. AB - Renal bleeding of iatrogenic origin was diagnosed in three patients with massive hematuria. Although percutaneous nephrostomy was the initial injury in all cases, the angiographic presentation was very variable. All cases were successfully managed with arterial embolization, using different techniques. Symptoms regressed totally in all patients avoiding surgical intervention. PMID- 2238289 TI - Coexistent xanthogranulomatous pyelonephritis and massive replacement lipomatosis of the kidney: CT diagnosis. AB - Replacement lipomatosis (RPL) is seen in patients in whom renal parenchyma is destroyed due to chronic calculous disease and inflammation. The triggering mechanism for xanthogranulomatous pyelonephritis (XGP) is also the same. We report a case in which RPL and XGP coexist in the same kidney. To our knowledge, this coexistence has not been previously reported. PMID- 2238290 TI - Splenic abscess arising by direct extension from a perinephric abscess. AB - A case of a perinephric abscess invading the spleen in a 25-year-old woman with bladder exstrophy is reported. Treatment utilized both percutaneous drainage and open surgery. Perinephric abscesses have not been previously reported to extend into the spleen. PMID- 2238291 TI - Sonographic pseudokidney after nephrectomy. AB - When interpreting renal sonograms, one should be aware of the possibility of mistaking fat and scarring in the renal fossa for a normal kidney in a patient with a history of prior nephrectomy. When in doubt, the ultrasound findings should be confirmed with a CT scan. PMID- 2238292 TI - Eccentric nephroscopy for the incarcerated nephrostomy. AB - Following a percutaneous stone extraction and demonstration of antegrade flow, conventional methods of traction and coaxial dilatation failed to allow removal of a Stamey-Malecot nephrostomy. An eccentric track was created for nephroscopy. Grasping forceps were used to cut the fibrous tissue from the "wings" of the nephrostomy tube to allow its easy withdrawal. The combined approach by the radiologist and urologist safely overcame the fibrous entrapment. PMID- 2238293 TI - Excessive accumulation of normal retroperitoneal fat mimicking a neoplasm: urographic/CT correlations. AB - Computed tomography (CT) was performed on four patients in whom excretory urograms revealed marked displacement of the kidneys and/or ureters. CT in each case was remarkable for the presence of excessive accumulation of normal retroperitoneal fat and failed to document the existence of a retroperitoneal neoplasm, lymphadenopathy, or other pathological mass. PMID- 2238294 TI - Application of urologic techniques to nonurinary calculi. PMID- 2238295 TI - Radiation therapy of early (stages I and II-A) seminoma of testis after initial orchiectomy. AB - With initial orchiectomy and radiation therapy, the prognosis of the patients with early (Stages I and II-A) testicular seminoma is nearing almost 100 percent. Thirty-two patients with Stage I and 13 patients with Stage II-A seminoma of the testis were treated with initial orchiectomy. This was followed by estimation biochemical markers and radiologic investigations. All the patients with Stage I disease received radiotherapy to the ipsilateral pelvic and para-aortic nodes. The patients with Stage II-A disease also received radiation therapy to the supradiaphragmatic regions. The disease-free survival in both groups of patients was found to be 100 percent. PMID- 2238296 TI - Management of superficial G2 (pTa and pT1) bladder cancer. AB - A total of 143 patients with superficial G2 (pTa, pT1) bladder cancer (48 G2pTa; 95 G2pT1) presenting between 1970 through 1987 were reviewed. Of 48 patients with G2pTa followed for up to eighteen years, G3 recurrence developed only in 1 (2.0%), and invasive cancer (greater than pT2) developed only in 2 (4.2%). They both received radiotherapy and have responded completely. There have been no cancer-related deaths. In contrast, in the 95 patients in whom the basement membrane had been breached (pT1), higher grade tumor (G3) developed in 11 (11.5%), and 15 (16%) had recurrences with invasion of muscle (greater than pT2). Among these there were 7 (7.3%) cancer-related deaths. PMID- 2238297 TI - Whole bladder photodynamic therapy: critical review of present-day technology and rationale for development of intravesical laser catheter and monitoring system. AB - Present-day whole bladder photodynamic therapy (WBPDT) is cumbersome and time consuming because cystoscopic and ultrasonic manipulations are necessary to position the light emitter within the bladder. More important, WBPDT is inherently unsafe and often ineffective since neither uniform photoirradiation nor accurate light dosimetry can be achieved with the techniques employed to photoirradiate the bladder wall. The intravesical laser catheter (IVLC) eliminates the need for cystoscopy and ultrasonography because passage of the treatment fiber into the catheter's central lumen automatically positions its light-diffusing tip within the center of the bladder. Use of the IVLC delivery system also assures accurate photoirradiation of the bladder wall since inflation of the catheter's balloon transforms the asymmetric bladder into a sphere of known diameter. The light sensor incorporated in the balloon wall provides a method to monitor light fluence and measure total light dose. When provided the parameters of bladder volume, laser energy output, and desired light dose, the computerized control system calculates treatment time and automatically adjusts the period of photoirradiation to compensate for variations in laser light production, energy losses during transmission, and for variations in light intensity resulting from the integrating sphere effect of the bladder wall. This delivery system also increases the safety of WBPDT since the monitor automatically discontinues treatment if any unsafe situation, with respect to light fluence, develops during photoirradiation. PMID- 2238298 TI - Stress incontinence: a new endoscopic approach. AB - We describe our experience in using a new endoscopic technique for suspending the bladder neck and urethra in 16 patients with stress incontinence. The procedure was started by dissecting the retropubic space, first with a sound and then with a Foley catheter before passing an absorbable suture from the abdominal fascia to the bladder neck using an elbowed needle introduced into the bladder through the neck and exteriorized through the urethra. The dissection of the retropubic space helped to form postoperative adherences which fixed the bladder neck and the urethra firmly to the pubic symphysis. The technique is simple, it does not require vaginal surgery, and the incidence of complications is minimal. PMID- 2238299 TI - Management of Peyronie disease by implantation of inflatable penile prosthesis. AB - Sixty-seven patients with advanced Peyronie disease were treated by implantation of an inflatable penile prosthesis (IPP). Twenty-eight of the 67 patients had documented total erectile failure. The remaining 39 patients had significant penile curvature causing "mechanical impotence" due to inability to achieve adequate vaginal penetration and chose implantation of an inflatable penile prosthesis (in some cases, combined with a straightening procedure) rather than one of the standard penile straightening procedures. Currently, 63 of the 67 patients have functioning prosthetic devices; in 3 other patients the device was removed because of infection, and 1 patient was dissatisfied and had the device removed. For impotent patients with severe Peyronie disease for whom other medical or surgical treatment is neither desirable nor suitable, we recommend implantation of an inflatable penile prosthesis combined with a possible straightening procedure. PMID- 2238300 TI - Use of distal Thiersch-Duplay urethroplasty for proximal hypospadias repairs in conjunction with short island pedicle flap. AB - Experience with 8 boys having proximal hypospadias with severe chordee and a foreshortened dorsal hooded foreskin is presented. Use of a distal Thiersch Duplay tube was incorporated in addition to an island pedicle flap to achieve the correct meatal location on the glans. One boy with perineal hypospadias required both proximal and distal Thiersch tube with an island flap interposition. Follow up of nine months to 3.5 years demonstrated excellent cosmetic and functional results with no recurrent chordee or urethral stenosis. The only fistula noted developed at the proximal Thiersch tube-island flap anastomosis in the boy with perineal hypospadias. Advantages of the aforementioned procedure include decreasing the risk of chordee on the basis of a foreshortened island pedicle flap, use of vascularized flaps, and completing the procedure in one stage with a satisfactory result. PMID- 2238301 TI - Radiologic staging of chest in testicular seminoma. AB - We investigated the usefulness of chest x-ray (CXR), conventional planar tomography (TOM), and computerized axial tomography (CAT) in evaluating patients with Stages I and II testicular seminoma. All patients had a CXR, and 22 patients had either TOM or CAT as part of initial staging. No occult pulmonary or mediastinal nodal disease was found during initial staging, and none of the patients manifested recurrence of tumor in these sites as a first event. Review of the literature corroborates our finding of a very small thoracic failure rate in early stage seminoma. Routine use of CAT or TOM is not indicated in staging these patients. PMID- 2238302 TI - Urodynamic tests for female geriatric urinary incontinence. AB - Most urodynamic tests currently in use in the evaluation of female urinary incontinence have not been applied to a community-based sample to determine their specificity. In this study of a random sample of noninstitutionalized elderly, 258 self-reported continent and 198 self-reported incontinent women sixty years and older, who participated in a household survey, underwent a clinic evaluation (history, physical examination, and urinalysis); of these 67 continent and 100 incontinent female respondents underwent urodynamic testing. The uroflowmetry, cystometry, and supine static urethral pressure profilometry (UPP) findings did not differ significantly between continent and incontinent subjects (whether based on a self-report or a clinician's diagnosis of urinary continence status). Standing static and dynamic UPP and lateral cystography showed significant differences between self-reported continent and incontinent respondents. The provocative stress test significantly distinguishes continence from incontinence, and stress incontinence from other types. The sensitivity of the provocative stress test was 39.5 percent, whereas its specificity is 98.5 percent. Urodynamic testing including uroflow study, static UPP, and lateral cystography should not be used as a screening test but rather selectively as a confirmatory test, and to determine the therapeutic approach, and to assess the outcome of therapy. PMID- 2238303 TI - Influence of high-energy shock waves and cisplatin on antitumor effect in murine bladder cancer. AB - The potential application of high-energy shock waves (HESW) for control of experimental bladder cancer was investigated. Subcutaneous 3-d murine bladder cancer (MBT-2) in C3H mice were exposed to HESW alone (250 to 1,500 shocks) or in combination with cisplatin (5 to 10 mg/kg, i.p.). Although HESW alone showed no influence on tumor growth, HESW/cisplatin combination therapy suppressed tumor growth more than cisplatin alone. Subsequent studies revealed that an air-fluid interface relative to tumor location played a pivotal role for the chemosensitizing effect of HESW. HESW treatment was able to enhance the cisplatin cytotoxicity only when the tumors were placed adjacent to the air-fluid interface. PMID- 2238304 TI - Oncocytic renal tubular adenoma (so-called oncocytoma) in seventeen-year-old girl. AB - Renal tubular neoplasms (adenomas or adenocarcinomas) are rare in children or young adults. Herein, we report an oncocytic renal tubular adenoma (so-called oncocytoma) that was found in a seventeen-year-old girl. Preoperative evaluation included aspiration of this tumor, and we suggest that preoperative aspiration is an important procedure in the diagnosis and management of suspected renal tumors in children and young adults. PMID- 2238305 TI - Raz double-prong ligature carrier for transvaginal bladder and bladder neck needle suspension. PMID- 2238306 TI - Partial resection of symphysis pubis. PMID- 2238307 TI - Simplification of double-dye test to diagnose various types of vaginal fistulas. PMID- 2238308 TI - Intravesical condyloma acuminatum with progression to verrucous carcinoma. AB - Condyloma acuminatum is a common form of venereal disease. Most patients with condylomata acuminata suffer from only the local cosmetic and irritative effects of the lesions. Few patients have progression to aggressive, regionally distributed lesions that can be life-threatening. We describe a forty-three-year old white woman who had a seventeen-year history of scleroderma with extravesical and intravesical condylomata acuminata. During two years of conservative management with transurethral excision, electrocoagulation, and intravesical chemotherapy, the disease progressed to involve the entire bladder and resulted in obstructive renal insufficiency that required anterior exenteration and urinary diversion. The natural history of the disease is described, and the relevant literature is reviewed. PMID- 2238310 TI - Advances in the management of prostatic diseases. Proceedings of a symposium held in conjunction with the annual meeting of the American Urological Association. New Orleans, Louisiana, May 15, 1990. PMID- 2238309 TI - In treating impotence, urology and sex therapy are complementary. AB - Urologists and mental health professionals are neither competitors nor adversaries. The principles of sex therapy represent a thoughtful and sensitive way to approach patients with almost any clinical problem so that they are more comfortable with the recommended tests or treatments. Sex therapy may be very helpful as an adjunct in treating "organic" as well as primarily emotional erectile dysfunction. We believe that with information we can help build a bridge between urologists and mental health professionals. PMID- 2238311 TI - Diagnosis and treatment of prostatic infections. AB - The diagnosis and management of prostatitis and pelviperineal pain is a challenge to the clinician. Careful examination of the prostatic fluid and bacteriologic cultures to differentiate bacterial from nonbacterial prostatitis are essential. Antimicrobial therapy is effective in the majority of men with acute or chronic bacterial prostatitis. Nonbacterial prostatitis is the most common type of prostatitis. The etiology is unknown and treatment with repeated antimicrobial therapy is ineffective. Alpha-blocking agents may relieve symptomatology. Pelviperineal pain may be of prostatic origin but other nonprostatic causes should be sought. PMID- 2238312 TI - Applications of prostate ultrasonography. AB - Transrectal ultrasonography is a relatively new imaging modality that may be useful in the evaluation and management of patients with prostate cancer. Although cancer may have a characteristic appearance, it cannot always be reliably differentiated from benign conditions. While this technique has clinical applications in staging, monitoring tumor response to therapy, and assisting in biopsy, it is unclear as to whether useful information is obtained in the evaluation of patients with palpable disease. The role of transrectal ultrasonography in patients with nonpalpable disease or as a screening tool has yet to be determined. Other diagnostic tests in conjunction with ultrasound may in the future prove to be useful. Carefully performed prospective investigations with state-of-the-art equipment are still needed to further define the role of this diagnostic modality. PMID- 2238313 TI - [Interlamellar refraction keratoplasty with central keratectomy of superficial corneal laminae in the correction of aphakia]. AB - Interlamellar refraction keratoplasty with central keratectomy of superficial laminae of the cornea was used to correct aphakia in 15 patients and the results followed up for 2.5-7 years. This method permits a simultaneous refraction and optic transplantation of the cornea. Corneal refraction was enhanced by 7.2-14.8 diopters (the mean value 11.03 diopters). The technique is an extraocular one and therefore may be widely used for aphakia correction, particularly in cases with superficial opacities of the cornea. PMID- 2238314 TI - [Surgical correction of astigmatism using kerato-resection methods]. AB - The authors analyze the results of surgical correction of hypermetropic and mixed astigmatism, carried out by two methods: clinoid resection of the cornea and clinoid resection of the cornea with tangent autoclinoplasty (i. e. implantation of the resected site to the tangent incision in strongly refracting meridian). Surgical technique has been mastered in experiments with isolated eyes and the mechanism of changes in corneal refraction, resultant from its resection, studied. Experiments with rabbit eyes have shown that after corneal resection cicatrization is over by the third month after surgery. 17 operations with classical clinoid resection and 17 ones with that and tangent clinoid autoclinoplasty were carried out in patients with corneal astigmatism of 2.0 to 6.25 diopters, the follow-up periods being from 6 months to 4 years. The mean reduction of astigmatism after the use of the aforesaid methods has made up 2.47 and 4.8 diopters respectively (according to the data of subjective examination of refraction). PMID- 2238315 TI - [A new method of scleroplasty in progressive myopia]. AB - The author analyzes the results of sclera fortification carried out in 154 patients (220 eyes) with progressive myopia by the method he developed, consisting in transplantation of dry solid multilobar perforated transplant of silica-dried sclera that retained its natural configuration in the course of preservation. The method is simple, safe for the patients, since compression of vorticose veins and optic nerve is ruled out, easily tolerated, and yields a high stabilizing effect (97 percent) as evidenced by a follow-up of 1.5 do 3 years. PMID- 2238316 TI - [Prospects of the use of decompression surgery of the optic nerve in atrophy of vascular etiology]. AB - The technique of decompression surgery on the optic nerve in vascular atrophy has been developed. Optic disk staining grew more intensive, visual field widened, and vision acuity improved after such surgery. Results of fluorescent angiography of the fundus oculi and ultrasonic dopplerography evidence an essential improvement of the blood stream in the central retinal artery after the operation. The positive effect of surgery persisted over the entire follow-up period (8 months). The authors consider that enlargement of the inner diameter of the posterior scleral ring permits a more loose disposition of the vessels and fibers of the optic nerve in this ring, this being conducive to better circulation in the optic disk and retina. PMID- 2238317 TI - [Clinical experience with the use of improved-design monolithic intraocular lens]. AB - A monolithic intraocular lens (IOL) design is described, made of with a total diameter of 8.5-9.0 mm. This design is intended for intracapsular fixation after extracapsular cataract extraction. Sixty operations with implantation of the improved monolithic IOL design were carried out in patients with age-associated cataracts. No complications were recorded. After surgery vision acuity aided by spectacle correction has been 0.5-1.0 diopters in 93.3 percent of patients. PMID- 2238318 TI - [Resistance to blindness and frequency-contrast characteristics of the eye with artificial lens]. AB - Contrast sensitivity of vision was examined by the frequency-contrast characteristics method (FCC) and vision resistance to glare studies with Niktoskop equipment in 48 patients with artiphakia. FCC was estimated from the curve shape as well as from the mean threshold contrast in all space frequencies. Blindness resistance was assessed from the period of mesopic vision acuity recovery (MVAR) up to 0.3 diopters after the glare flash. The group included 28 patients with iris clips lenses and 20 with posterior-chamber lenses. Patients with vision acuity of 0.8-1.0 diopters were referred to the first and those with vision acuity of 0.5-0.7 diopters to the second category. The mean threshold contrast, whose normal value is 8.0 +/- 0.7 percent, was drastically elevated 3 months after surgery in all the patients and only in a year normalized in the first-category patients with iris clips lenses or posterior-chamber lenses after posterior chamber dissection. Blindness resistance of patients with intraocular lenses was on the whole worse than in normal eyes: MVAR was by 26.2 +/- 0.7 percent higher than the normal value and normalized to reach 29.0 +/- 0.6 sec only in a year in the first-category patients with posterior-chamber lenses whose posterior capsule was not dissected. Therefore, FCC and MVAR values depend on the end vision acuity and type of intraocular lens and are on an average better after implantation of posterior-chamber lenses and not of iris clips lenses. PMID- 2238319 TI - [Ophthalmologic care of patients injured in accidents]. AB - The authors analyze the results of treatment of patients whose organ of vision was injured in accident. They point out a complex of measures promoting a relatively favorable optic and cosmetic outcome of injuries and discuss the shortcomings of ophthalmologic service. Various aspects of the problem are considered to develop practical recommendations on effective care of the injured patients. PMID- 2238320 TI - [Results of exophthalmometry. Incidence of ciliary-choroid detachment]. AB - Examinations of 87 patients with different positions of the eyeball in the orbit have revealed that if the eyeball sinks even slightly deeper in the orbit than normally, collapse of the cornea is observed during cataract extraction and ciliary-choroid detachment develops during the postoperative period. If the eyeball protrudes forward no corneal collapse or ciliary-choroid detachment occur. PMID- 2238321 TI - [Results of fluorescence angiography of the iris in surgical treatment of recurrent anterior uveitis]. AB - Seventeen patients (17 eyes) with anterior recurrent uveitis, aged 18 to 58, were examined by fluorescent iris angiography before and after surgery, extracapsular cataract extraction with vitrectomy. The findings evidence disordered microcirculation in the iris in anterior recurrent uveitis. The severity of the micro-circulatory shifts depended on the disease standing and the period elapsed since the last uveitis recurrence. Surgical treatment of the condition promoted recovery of the iris angioarchitectonics and the time parameters of the vascular system microcirculation. PMID- 2238322 TI - [Use of thrombin in the prevention and arrest of intraocular hemorrhage during vitrectomy in traumatic hemophthalmos]. AB - Thrombin obtained from donor blood plasma was used to achieve hemostasis during vitrectomy for traumatic hemophthalmos. Analysis of the results of surgery in 21 patients and in 28 controls has shown a manifest hemostatic activity of the agent. If introduced intravitreally, it induced no local reaction of tissues. Thrombin is recommended for clinical application. PMID- 2238323 TI - [Histological changes in the tissues of the posterior segment of the eye in intravitreal YAG-laser coagulation]. PMID- 2238324 TI - [Effects of phosphaden on hemodynamics of the eye in patients with post thrombotic retinopathy]. AB - A course of treatment with phosphaden, a rheologic agent, has been administered to 33 patients with postthrombotic retinopathy. The treatment resulted in improvement of the fundus oculi status and of vision acuity in the majority of patients. Rheo-ophthalmography data indicate an improvement of blood supply to the eyes after such treatment. The authors claim that ocular hemodynamics improvement is related to correction of impaired blood rheology. The findings evidence the efficacy of phosphaden in the management of postthrombotic retinopathy. PMID- 2238326 TI - [Electrophysiological diagnosis in partial optic nerve atrophy syndrome]. AB - Vision conduction routes were examined in 75 patients with the syndrome of optic nerve partial atrophy by recording the visual evoked potentials, threshold of electric sensitivity emergence, critical frequency of phosphene disappearance, electroretino- and electroneurograms. The findings of these examinations correlated best of all with the clinical picture when visual evoked potentials (latency increase, decrease of the amplitude with atrophy augmentation, interhemispheric asymmetry in chiasmal and retro-chiasmal involvement) or the critical frequency of phosphene disappearance (reliably reduced if a disease was developing) were recorded. Introduction of electrodes with therapeutic and diagnostic purpose permitted assessment of optic nerve function from the electroneurogram amplitude and time parameters. PMID- 2238325 TI - [Novocaine blockade of the carotid sinus zone in multimodal treatment of optic vascular neuropathies]. AB - Carotid sinus zone blocking with 2 percent procaine solution was used in multiple modality treatment of 91 patients with optic vascular neuropathies. Visual function improvement was achieved in 85.1 percent of patients. The effect was the best in the patients with sector vascular papillitis (91.7 percent) and the lowest in sclerotic atrophy of the optic nerve (79.3 percent). PMID- 2238327 TI - [Mechanisms of organic drug electrophoresis]. AB - Riboflavin, riboflavin mononucleotide, and fluorescein penetration from the ocular bath without electric current (control), from the anode, from the cathode, and without current after preliminary galvanization was studied in rabbit eyes. Penetration of organic drugs into intraocular fluid in electrophoresis was found to be increased not only from the adequate pole of the active electrode, but from the contrary pole as well. Galvanic current sharply abated the barrier function of the cornea. Therapeutic electrophoresis of the eyeball permits the use of many component solutions with drug ions of different charge. PMID- 2238328 TI - [Fluorescein movement in a transparent lens]. AB - Fluorescein movements in the lens laminae of isolated porcine eyes were examined by biomicroscopy. The stain disseminated in two directions: from the lens nucleus to capsules and fluorescein release into the intraocular fluid and from the outer laminae of the equatorial zone to the nucleus. Lecozyme, a proteolytic agent, accelerated fluorescein movement in both directions. The method suggested by the authors permits an objective assessment of fluorescein movement in the lens, which appears to reflect the processes of extracellular fluid ultrafiltration in the lens. The data evidence the possibility of effecting the extracellular intralenticular fluid microcirculation by proteolytic enzymes. The suggested technique may be useful in studies of cataract pathogenesis and of anticataract action of various drugs. PMID- 2238329 TI - [Determination of the medium molecular level in the evaluation of the effectiveness of quantum hemotherapy in uveitis]. AB - Estimation of blood serum medium-molecular level is recommended for assessment of the therapy efficacy in uveitis patients. Therapy of these patients by UV irradiation of the blood with Soviet Izolda MD-73M apparatus is described, that proved highly effective: 93 percent of patients were cured and only 5 percent developed recurrences. Clinical status of the patients correlated with the blood serum medium-molecular level. PMID- 2238330 TI - [Laser irradiation: study of general and local mechanisms of its action in irradiation of the eyeball. An experimental study. 3]. AB - Rabbit ocular tissues, brain, and blood were examined before and after irradiation of the eyeball with He-Ne laser. Scanning electron microscopy, radioimmunoassay, and biochemical methods were employed in the study. The findings evidence that irradiation of the eyeball results in reduced lipid peroxidation activity and elevated antiradical defense enzymes activity not only in ocular tissues but in the corresponding brain hemisphere and blood, which fact appears to be due to direct effect of laser radiation on the blood and brain via the optic nerve that may be a light conductor for a certain wavelength. Local increase of the eyeball corneal permeability in laser irradiation may be explained by activation of membrane phospholipases, combined with electrolyte shifts; morphologically and functionally it manifests by changed endotheliocyte stereotopography. PMID- 2238331 TI - [Comparative tonometric and perimetric examinations in open-angle glaucoma]. PMID- 2238332 TI - [Changes in parameters of the eyeball during the 1st year of life]. AB - The authors have examined the eyes in a group of healthy full-term infants during the first year of life. Anatomic and optic parameters of the eyes of newborns aged 2 hrs to 7 days and 1-year-old infants were under study. The data are important for ophthalmic surgery of infants of this age group. PMID- 2238333 TI - [Ophthalmological aspects of Reiter's disease]. AB - Clinical picture and course of eye involvement were studied in 254 patients with Reiter's disease. Altogether 130 patients suffered from conjunctivitis of varying severity, 23 from keratitis, 21 from episcleritis, 20 from uveitis, 2 from detachment of the retina, and 5 from secondary glaucoma. Chlamydia were detected in one third of conjunctivitis patients in scrapings off the conjunctiva. The eyes may be accidentally infected by agents from the urogenital organs if the patient does not observe the hygienic rules. Uveitis developed as a rule after a prolonged course of Reiter's disease. They were resistant to antichlamydial therapy because of autoimmune factors that underlay the condition pathogenesis. Deposits of immune complexes on antigens of ocular vascular coating were detected with the use of monospecific antiglobulin sera in 7 of 10 patients with active uveitis symptoms. The risk of Reiter's disease development in HLA B27 carriers is 27.17 times higher than the mean incidence of this disease in the population. HLA A9 and B40 antigen combinations occurred 7 times more often in uveitis patients than in reference subjects, A1 and B27 combinations were 4-5 times more incident. PMID- 2238334 TI - [Amyloidosis of fundus oculi tissues in senile maculopathy (a clinico morphological study)]. AB - The authors analyze the findings of clinical and morphologic studies of the pathologic changes in fundus oculi tissues of 3 patients who died with senile macular dystrophy, examined in life time by ophthalmoscopic technique with transformed light. The sclera, vascular coating, retina, macula retinae, optic nerve region were thoroughly studied with the use of review histological, histochemical methods, selective test for amyloid, thiazine red fluorescent histochemical method, and thioflavin T fluorescence. In 2 of the 3 cases amyloid degeneration in the presence of amyloid deposits in choroid vessels, arterial plexus vessels round the optic nerve presence of amyloid deposits in choroid vessels, arterial plexus vessels round the optic nerve orifice, in Bruch's membrane and in the sclera. Retinal vessels, optic nerve and its coatings were intact. Further investigations are to follow. PMID- 2238336 TI - [A case of progressive facial hemiatrophy]. PMID- 2238337 TI - [Case of anaerobic infection in penetrating injury of the eye]. AB - A patient with penetrating wound of the eye is described, whose wound has been contaminated with anaerobic infection. Clinical picture of anaerobic panophthalmitis has been rather typical, with the infection penetrating into soft tissues of the orbit. Evisceration of the eyeball was performed. Multiple modality treatment was carried out. The infectious process has not progressed beyond the orbit. The diagnosis has been confirmed bacteriologically. PMID- 2238335 TI - [Syndrome of the superior oblique muscle rigidity: clinico-anatomical aspects and results of treatment of 8 patients]. AB - Tenectomy of the superior oblique muscle resulted in complete disappearance of Brown's syndrome in 7 out of 8 children operated on. In view of this, it can be a method of choice in treatment of the syndrome. There was the first clinical case of an additional abnormal attachment of the superior oblique muscle tendon to the sclera. In another patient an abnormal marked vascularization of the tendon identified histologically had the appearance of a muscular structure at the site of the tendon seen at the operation. PMID- 2238338 TI - [Syphilitic lesions of the organ of vision (review)]. PMID- 2238340 TI - [Characteristics of vestibulo-ocular interaction in patients with unilateral lesion of the peripheral part of the vestibular system. Mechanisms of inhibition of the vestibulo-ocular reflex (report 2)]. AB - This paper gives a description of the mechanisms of inhibition of the vestibulo ocular reflex by the gaze mechanisms in patients with unilateral lesion of peripheral compartments of the vestibular system at the stage of decompensation and subcompensation. PMID- 2238339 TI - [Results of combined use of taufon and timolol in the treatment of patients with open-angle glaucoma]. AB - The effect of taufon and timolol maleate combination on intraocular pressure and ocular hemodynamics was studied in 44 patients (63 eyes) with primary open-angle glaucoma. Combined administration of these agents elevated almost twofold the fluid discharge efficacy coefficient and normalized Becker's coefficient in 68.6 percent of patients. The patients were followed up for 8 weeks. Taufon addition to timolol modified the action of this latter drug, normalizing the ocular hemodynamics. PMID- 2238341 TI - [Comparative analysis of the variants of experimental intra-aural pharmacophysical intervention]. AB - The permeability of the blood-brain barrier of rabbits was measured in response to different methods of endaural pharmacophysical intervention and intravenous injection of radioactive DL (2,3-3H2) leucine. The concentration of labelled leucine was measured in the inner ear fluids. The experiments were performed using 28 rabbits. The maximum amount of the drug entered the labyrinth as a result of endaural superphonoelectrophoresis. In this case the positive effect was reached after a smaller number of therapeutic sessions. This method is recommended for clinical treatment of cochleovestibular lesions. PMID- 2238342 TI - [New symptom in early diagnosis of bilateral acoustic neuroma]. AB - Eleven patients were admitted to the hospital with the diagnosis of unilateral tumor of the vestibulocochlear nerve at the stage of clinical manifestations or at a well advanced stage. Their otoneurological examinations revealed a microtumor at the side opposite to the major tumor node. Of great diagnostic importance were vestibulometric data which showed lack of vestibular excitation on both sides: in some cases it was not recorded during caloric tests while in other cases it was not recorded during caloric or rotation tests. In view of the lack of the vestibular response on the "healthy" side, it was supposed that there was a microtumor there. In all cases this diagnosis was confirmed either by computer tomography or by CT and surgery. This symptom can be very helpful for an early detection of a microtumor or the vestibulocochlear nerve on the side opposite to the major tumor node. It is emphasized that special attention should be given to arm displacement, during caloric tests. PMID- 2238343 TI - [Neurosensory hearing loss in children with acute and chronic otitis media diagnosed by the measurement of short-latency auditory evoked potentials]. AB - The sensory component of acute otitis media, especially in children, has been poorly studied. In order to identify the importance of ERA for the diagnosis of the neurosensory component of hypoacusis associated with acute otitis media, we examined 56 children. In all the patients ERA were recorded, and in children over 3 years old tonal audiometry was performed. Comparison of ERA and audiographic data showed that in some cases ERA was helpful to reveal the sensory component of impaired hearing which was not seen audiographically. This allowed detection of preclinical stages of perceptive disorders. It is concluded that in young children (younger than 3 years) ERA can help to measure the level of conductive hearing impairment as well as to detect inflammatory changes in the inner ear structures. PMID- 2238344 TI - [Otogenic and rhinogenic brain abscesses in children]. AB - Otogenic and rhinogenic abscesses of the brain in children (25 cases) constitute 4.4% of neurosurgical pathologies and 26.9% of all brain abscesses in children. Rhinogenic abscesses (10 cases) were located in the frontal lobes and otogenic abscesses (15 cases) were found supra- or subtentorially. It is difficult to diagnose brain abscesses in children. In this respect computer tomography is very valuable. All the above patients underwent surgical intervention, which included such methods as aspiration, drainage and block removal. The lethality rate was 36%, although during the last 5 years (9 cases) no lethal cases were recorded. PMID- 2238345 TI - [An automated thermographic complex: new possibilities of the diagnosis of ORL disease]. AB - The Kiev Research Institute of Otorhinolaryngology has built an automatic diagnostic system that includes a Raduga thermograph and a CM-1403 computer. The diagnostic algorithms are based on the thermosemiotics of ENT inflammatory diseases developed by the authors. The advantages of the system are: production of a hard copy of thermograms, registration and long storage of information, mathematical treatment of thermal images, data base and rapid search for the thermogram needed, screening diagnosis based on the "healthy-sick" principle. PMID- 2238346 TI - [Effect of the functional state of the eustachian tube on the sanative process after ear surgery]. AB - After radical operation 40 patients, who showed exacerbation of chronic purulent otitis media, were treated for problems of the Eustachian tube. All the patients showed granular salpingitis. The patients were subdivided into two groups with respect to the therapeutic method used: 1) in 18 patients, a punctured bougie catheter was inserted into the Eustachian tube. The catheter was used to wash the tube with antiseptics (dioxydin, balyse-2, microcide) and to blow oxygen for 20 min; 2) in 22 patients, the permeability of the Eustachian tube was restored by bougieurage; then an antibiotic ointment was administered and, after purulent discharge stopped, solcoseryl ointment was placed. It was concluded that the incidence of exacerbations of chronic purulent otitis media after radical operation decreased, when the Eustachian tube underwent specific therapy. PMID- 2238347 TI - [Ultrasonic ethmoidotomy combined with intracavitary magnetotherapy in chronic polypous ethmoiditis]. AB - The efficacy of ultrasonic ethmoidectomy combined with magnetic therapy was investigated in 90 patients. Ultrasonic ethmoidectomy was applied with the help of a LORA system consisting of a generator and an acoustic unit connected to a waveguide with a spoon-shaped end (44 Hz frequency and 35-40 microns amplitude). Under visual control the ultrasonic spoon was inserted into the meatus nasi medius, and the injured medial, superior and some anterior cells of the ethmoidal bone were opened. Bone trabecules of the cells were removed together with the polypous mucous membrane and polyps, by moving the concave surface forwards and keeping the long axis of the bent portion of the spoon in the vertical position. Follow-up of the treated patients during 6 months to 4 years revealed the absence of polyps in 79.7%. Repeated application of this treatment in the case of severe recurrent forms of polypous ethmoiditis improved the therapeutic efficacy. PMID- 2238348 TI - [Study of the changes in microcirculatory bed in children with vasomotor rhinitis based on biomicroscopy of conjunctival blood vessels]. AB - Thirty-eight patients with vasomotor rhinitis, aged 6 to 15 years, were examined by means of biomicroscopy of eyeball conjunctiva vessels. As a result, the following microcirculatory disorders were detected: vessel enlargement, diameter nonuniformity, pathological convolution and red blood cell aggregation. Patients with allergic lesions showed most significant structural changes. The prevalence of functional changes over structural ones in the eyeball conjunctiva of children with neurogenic vasomotor rhinitis can be used as a differential diagnostic indicator. PMID- 2238349 TI - [Hyperbaric oxygenation in the postoperative treatment of children with cicatricial laryngostenosis]. AB - Hyperbaric oxygenation (HBO) was used in the combined treatment of 20 children, aged 2 to 14 years, after reconstructive surgery of the larynx. All the patients had been exposed to tracheostomy. As a result, optimal regimens of compression and decompression of operated children were developed which were 0.025 ata/min and 0.04 ata/min, respectively. HBO was most effective when whole-body and regional hypoxia was applied simultaneously. The optimal pressure in an altitude chamber was 0.9 to 1.0 ata for as long as 40 to 50 min. HBO made it possible to shorten the degenerative-inflammatory process. Positive changes in pH of the wound were regarded as an indication of reductive aerobic metabolism there. PMID- 2238350 TI - [Various aspects of endonasal corrective surgery]. AB - This paper discusses the results of 649 rhinoseptoplastic and 139 rhinoconchoplastic operations performed according to modified methods of Killian and Cottle. The surgical intervention led to the following complications: 1) deformation of the nasal septum in the vestibule area (11 patients); 2) perforation of the nasal septum of atrophic origin (15 patients); 3) saddle-like deformation of external nose (7 patients); 4) vibration of the nasal septum which occurred in most patients after total resection of the cartilage and vomer. The author elaborated methods of plastic operations of: the vestibule of the nose in order to prevent its postoperative deformation, the vomerine zone in order to preserve intraosseous vessels in the foramen incisivum area, the ridge of the nose in order to avoid the saddle-like nose, and implantation of the zigzag cartilage graft in order to prevent vibration of the nasal septum. Analysis of the rhinoconchoplastic operations allowed the author to propose medial positioning of the nasal concha in the case of hypotrophic rhinitis and implantation of autocartilage into the nasal concha in order to enlarge it in the case of hypotrophy. PMID- 2238351 TI - [Combined treatment of stage III laryngeal cancer with different schedules of radiotherapy and surgery. Evaluation of preventive methods of the treatment of regional areas (cooperative randomized study)]. AB - In 1980-1987, a cooperative randomized study of 363 patients with stage III laryngeal cancer (T1-3N0-1M0) was carried out. In 249 patients tumor was located in the vestibular space and in 114 in the vocal cord area; 78.5% of the patients had no regional metastases (N0) and 21.5% had metastases (N1). Combined therapy was applied to 251 patients, 135 of which were first exposed to radiotherapy and then to surgery and 116 were first exposed to surgery and then radiotherapy. In 71 patients, regional zones underwent preventive treatment (in 24 patients elective radiotherapy and in 47 preventive removal of the cervical fat were used). In 112 patients, the therapeutic protocol was modified due to different reasons (69 patients underwent only surgery and 43 radical radiotherapy). The therapeutic results were assessed in terms of three parameters: incidence of relapses and regional metastases, relapse-free time, and survival. This approach revealed no significant differences in the efficacy of the different protocols of the combined treatment. The 5-year survival rate of the patients with vestibular and cord space tumor was 77.9% and 80.7% respectively, when treated according to the radiotherapy + surgery protocol, and 82.8% and 89.2%, respectively, when treated according to the surgery + radiotherapy protocol. Comparison of preventive approaches showed that the 5-year survival rate increased by 92% as a result of removal of the subcutaneous fat from the neck area. PMID- 2238352 TI - [Clinico-morphological substantiation of the selection of optimal variants of therapeutic tactics in non-epithelial tumors of the nasal cavity and paranasal sinuses]. AB - Out of 227 cases of nonepithelial tumors of the nasal cavity and paranasal sinuses, 147 patients with benign neoplasms had a good prognosis while 80 patients with malignant neoplasms had a poor prognosis. The efficacy of their therapy can be enhanced on the basis of a differential approach, measurement of tissue radiosensitivity and adequate surgical intervention. PMID- 2238353 TI - [Clinico-morphological characteristics of esthesioneuroblastoma with extensive dissemination of the neoplastic process]. AB - Eight disseminated esthesioblastomas were investigated. The specific features of these cases were: prolonged development of the disease prior to correct diagnosis (up to 2 years), tumor dissemination outside the nose and paranasal sinuses, and mixed morphological changes indicating various tumor types. PMID- 2238354 TI - [Methodological principles of otorhinolaryngological ambulatory examinations and medical rehabilitation of workers exposed to intensive occupational noise and air pollutants]. AB - This paper presents principles of otorhinolaryngological mass-scale examination of industrial workers exposed to noise and dust. They require not only early detection of pathologies of the hearing organ and upper airways but also assessment of the health status of each person and identification of groups at risk. Dynamic observation over healthy and sick subjects as well as proper application of prophylactic and therapeutic measures helps maintain good health and high performance of industrial workers. PMID- 2238355 TI - [Otomycoses in the Kuznetsk region and organization of medical services for this group of population]. AB - In the Kuzbass region the author examined 238 patients, aged 15 to 80 years, with persistent otitis or inflammatory pathologies of the ears that could not be cured by routine therapy. As a result, in 90 patients (37.8%) otomycosis was diagnosed. Mycosis of the external acoustic meatus was identified in 43 patients (55 mycotic ears or 52.4%), fungal otitis media was found in 21 patients (22 ears or 20.9%), and mycosis of the postoperative cavity was detected in 26 patients (28 mycotic cavities or 26.7%). The following fungi occurred most frequently: Aspergillus niger (75.2%), Candida albicans (6.7%), and Penicillium flavum March (3.8%). In the presence of fungi the bacterial growth was less significant, thus indicating the predominant role of fungi during otomycosis. Nitrofungin and clotrimazol in combination with 1% decamine ointment were effectively used in the treatment. A good antipruritic drug was 7% chloracetophose ointment. Out of 90 patients complete regression was recorded in 84 cases, with 6 patients having relapses. PMID- 2238356 TI - [Hereditary deafness associated with eye pathology]. PMID- 2238357 TI - [Parapharyngeal abscess in a child]. PMID- 2238358 TI - [Foreign body of the maxillary sinus]. PMID- 2238359 TI - [Osteoma of the maxillary sinus]. PMID- 2238360 TI - [Suppurative sphenoiditis complicated by thrombophlebitis of the cavernous sinus and meningitis in a pregnant woman]. PMID- 2238361 TI - [Modification of the lighting system of Mezrin's bronchoesophagoscope]. PMID- 2238362 TI - [A device for applying sutures]. PMID- 2238363 TI - [Report on the activities of the All-Union Scientific Society of Otolaryngologists 1988]. PMID- 2238364 TI - [History of the M.F. Vladimirskii Otorhinolaryngological Clinic of the Moscow Scientific Institute of Clinical Research (the pre-war period)]. PMID- 2238365 TI - [Short-latency auditory evoked potentials in patients with acoustic neuroma and relatively normal hearing]. AB - Out of 37 patients with verified neurinoma of the vestibulocochlear nerve 11 had essentially normal hearing and showed significant disorders of BERA (of the scissors type). This proved high sensitivity of computer audiometry (CA) applied to examine patients suspected for retrocochlear lesions. It is recommended to use CA when examining patients complaining of unilateral hearing impairment in order to rule out neurinoma of the 8th cranial nerve, especially at its early stage. PMID- 2238366 TI - Introduction to endoscopy. AB - Endoscopy is an area of rapidly growing interest within veterinary medicine. This is understandable, because it is a relatively noninvasive procedure in which a tremendous amount of diagnostic data may be obtained. The purpose of this article is to introduce the novice to the equipment and potential uses of endoscopy. PMID- 2238367 TI - Veterinary endoscopy. PMID- 2238368 TI - Upper gastrointestinal endoscopy. AB - Upper GI endoscopy is a frequently performed endoscopic procedure that is particularly suited for the diagnosis of upper GI diseases with a luminal or mucosal location. Contraindications are few and complications are rare. Procedures that can be performed during upper GI endoscopy include mucosal biopsy, brush cytology, aspiration of duodenal fluid for culture and cytology, foreign body retrieval, bougienage of strictures, and endoscopic placement of gastrostomy tubes. Unresolved issues that face veterinary endoscopists include the interrelationship between contrast radiology and endoscopy, the advisability of routine combination of upper and lower GI endoscopy, the reasons for discordance among clinical signs, endoscopic appearance, and biopsy findings, and the role of post-treatment biopsies. PMID- 2238369 TI - Endoscopy of the lower gastrointestinal tract. AB - Colonoscopy is an extremely valuable diagnostic technique. It allows the veterinarian to visualize the lower gastrointestinal tract and obtain tissue for a definitive diagnosis with a noninvasive approach. This article reviews the indications, contraindications, instrumentation, and technique of endoscopy of the lower gastrointestinal tract. PMID- 2238370 TI - Rhinoscopy. AB - This article presents a diagnostic protocol for nasal disease evaluation that provides consistent success in diagnosis of chronic cases. The protocol includes history, physical examination, blood clinical pathology assessment, radiographs, culture and sensitivity tests, rhinoscopy, histopathology, fungal serology, and allergy screening. The sequence of diagnostic procedures and their techniques are discussed, and rhinoscopic appearance of the normal nasal cavity is presented, along with findings of commonly seen nasal diseases, including neoplasia, mycotic rhinitis and sinusitis, foreign body obstruction, dental disease, allergic rhinitis, bacterial rhinitis, and idiopathic rhinitis. Rhinoscopy is a highly effective diagnostic technique with minimal morbidity and mortality that has virtually eliminated the need for exploratory rhinotomy. PMID- 2238371 TI - Laryngoscopy. AB - The larynx normally functions in vocalization, deglutition, and respiration. There is no substitute for direct laryngoscopy in animals suspected of having laryngeal disease. Clinical signs that should alert the veterinarian include cough, choking while eating or drinking, exertional cyanosis and syncope, noisy breathing, inspiratory dyspnea, stridor, and significant change in sound production. Controlled anesthesia is mandatory for animals with suspected laryngeal disease because many of these patients have compromised respiratory function. Laryngoscopy is used to note abnormalities in the shape, color, and motility of the larynx with special attention to correlating the movement of the arytenoid cartilages and vocal folds with the respiratory cycle. PMID- 2238372 TI - Tracheobronchoscopy. AB - Fiberoptic tracheobronchoscopy is a safe and rewarding technique for the diagnosis and management of a wide spectrum of respiratory tract diseases. A nomenclature system has recently been developed that allows the systematic identification of canine endobronchial anatomy during bronchoscopy. This system results in an improved ability to communicate bronchoscopic findings and provides a basis for performing a thorough bronchoscopic examination. Complications of tracheobronchoscopy are uncommon, but patients must be carefully monitored during the procedure because complications may be severe and life-threatening when they occur. Special techniques enhance the diagnostic spectrum of bronchoscopy and include brush cytology, forceps biopsy, bacterial culture, transbronchial lung biopsy, transbronchial needle aspiration, and bronchoalveolar lavage. PMID- 2238373 TI - Cystoscopy. AB - Cystoscopy is a diagnostic and therapeutic procedure commonly employed in human medicine but that has received limited application in small animal practice. Readily applicable, cost-effective instruments are available for use in the dog and cat. The urethral opening, urethra, bladder, and ureteral openings can be effectively assessed, and samples can be collected for histopathology, cultures, and stone analysis. Cystoscopy is indicated for assessment of chronic cystitis, hematuria, tenesmus, increased frequency of urination, urinary incontinence, alteration of urinary stream, trauma, and cystic and urethral calculi. Most cases can be evaluated transurethrally; the rest can be assessed by prepubic percutaneous cystoscopy. PMID- 2238374 TI - Thoracoscopy. AB - This article presents endoscopic evaluation of the pleural cavity, or thoracoscopy, an effective diagnostic technique that can be employed to provide additional diagnostic information in cases of intrathoracic disease. The techniques of thoracoscopy are described, and normal and abnormal findings are discussed. Thoracoscopy allows visual examination of the pleural space and surrounding structures without surgical exploration. The stress, expense, morbidity, and mortality of thoracoscopy are far less than those of thoracotomy. Disease for which thoracoscopy has been employed diagnostically include primary and metastatic neoplasia, hilar lymphadenopathy, pericardial effusion, spontaneous pneumothorax, and diaphragmatic hernia. Therapeutically, thoracoscopy has been used for drainage of pericardial effusion. PMID- 2238375 TI - Avian endoscopy. AB - Endoscopic techniques in birds provide invaluable information on the medical care and husbandry of avian species. The instruments required to perform these examinations have been adapted from human arthroscopic instruments. With the advances in avian anesthetic techniques, endoscopic techniques can be readily and successfully applied to the avian patient in a general practice setting. PMID- 2238376 TI - The future of veterinary endoscopy. AB - The developing areas of video endoscopy, endoscopic ultrasonography, and small bowel endoscopy are discussed in this article, and new endoscopic approaches to strictures and bleeding lesions of the gastrointestinal tract are presented. The potential applications of these techniques in veterinary medicine are left to the imagination of the reader. PMID- 2238377 TI - [The adenohypophyseal response and effect of GnRh (Dirigestran inj. Spofa) administration in cows in the postpartum period]. AB - Radioimmunological investigation (RIA) of the level of pituitary FSH in the peripheral blood of cows after parturition demonstrated that this level increased successively. The FSH value of 32.93 +/- 3.71 ng per 1 ml, recorded the fourth to sixth day post partum, increased to as much as 57.78 +/- 40.98 ng per 1 ml 40 days after parturition. The LH level changed only slightly over the same period (from 1.12 +/- 0.21 ng per ml to 1.72 +/- 1.15 ng per ml). The concentration of progesterone in the blood of the cows was about 0.40 ng per ml during the first 15 days after parturition, but from the 25th day post partum it trebled, on an average (1.53 +/- 1.19 - 1.59 +/- 1.25 ng per ml). The response of the adenohypophysis of the cows to the administration of 200 micrograms of synthetic gonadoreline (spec. Dirigestran inj. Spofa) increased with increasing length of time from parturition. FSH concentration increased less markedly during the first 28 days p.p. and this increase was not uniform in time (the average increase was 1.5 to three times); in the later period the highest increase 300-500% was recorded, as a rule, 120 minutes after GnRH administration. The situation was similar in the increase in LH concentration in peripheral blood, but after the 26th day post partum the average increase in LH accounted for 500 to 600%. The concentration of progesterone in peripheral blood increased by more than 300%, on an average, from the 25th day after parturition. This testifies to the first post partum ovulation and to the formation of a new yellow body in the majority of cows under study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238378 TI - [Morphological changes and sperm decapitation as a cause of fertility disorders in breeding stock]. AB - Decapitation of spermatozoa was recorded in a young boar as a consequence of epididymitis and in a young dog (mastiff) and a young bull (Brown Swiss breed) as a congenital cause of the subfertility and sterility of the affected animal. Decapitation of spermatozoa as a consequence of an inflammation led to the sterility of the breeding male and affected 52 to 68% of the spermatozoa. The motility of the spermatozoa was reduced considerably (10 to 20%) and the flagella were not observed to move without the heads. In cases of congenital decapitation of spermatozoa, sperm motility in the dog and bull was reduced, but the flagella were observed to move without the heads. Decapitation affected 15 to 42% of the spermatozoa and most frequently it was accompanied by a narrowing of head base and by the presence of a protoplasmic drop, located proximally. Further developmental changes, affecting the flagella of the sperms, were observed in the dog. The mentioned morphological changes led to infertility in the dog and to a substantial reduction of fertility in the bull. After natural mating of the bull with a superovulated cow, the ten eggs obtained included four blastocysts, two were degenerated, and four were unfertilized. PMID- 2238379 TI - [Quantitative micromorphological study of the ovaries in sheep after estrus synchronization and superovulation in the autumn mating season]. AB - The quantitative micromorphological changes of tertiary follicles and corpora lutea (CL) were studied in ewes in the autumn mating season after oestrus synchronization, induced by administration of PGF2 alpha (Oestrophan Spofa) at a rate of 125 micrograms, and after superovulation, induced by administration of PMSG (Antex Leo, Denmark) at a rate of 1000 I. U., or PMSG at rates of 750 and 1000 I. U. together with 50,000 I. U. vitamin A (Axerophthol Spofa). The highest number of ovulations was obtained in ewes treated with 1000 I. U. together with vitamin A (3.4 +/- 3.0) and after administration of 1000 I. U. PMSG alone (2.6 +/ 2.74). The highest number of tertiary follicles was recorded in ewes after administration of PGF2 alpha. The proportion of tertiary atretic follicles was the highest in ewes after administration of PMSG (64.6%). The occurrence of the luteinizing form of atresia was recorded only in ewes treated with PMSG (4% of the total number of atretic follicles). Using the caryometric analysis of the luteal cells of corpora lutea, the ewes of the experimental groups had two-peak variation curves; this corresponds to the theory of the presence of two luteal types in the tissue of the corpus luteum in ewes. As determined morphometrically, the smallest proportion of connective tissue out of the total volume of ewes' ovaries was found after administration of 1000 I. U. PMSG together with vitamin A. Administration of vitamin A together with PMSG had a favourable influence on the over-all follicular response, on the average number of ovulations, and on the proportion of non-atretic follicles. PMID- 2238380 TI - [Use of filter paper for blood specimen collection in poultry for use in the detection of antibodies to Newcastle disease virus]. AB - Trials were conducted to verify the possibility of poultry blood sampling with filter papers for subsequent examination of the eluates for the presence (and level) of haemagglutination-inhibition antibodies against the Newcastle disease virus (NDV). Qualitative examination was performed in 294 paired samples of sera and eluates, representing 10 selective sets, coming from three vaccinated poultry flocks. The numbers of positive sera (dilution ratios 1:20 and higher) and positive eluates of filter papers (dilution ratios of 1: 2 and higher) were compared and it was found that there were 238 positive paired samples (81%) and 30 were negative (10.2%), hence, there were like reactions in 268 paired samples (91.2% of the total number of samples examined). It was only in 25 paired samples that positivity was recorded just in the sera: 22 times with a titre of 1:20 and three times with a titre of 1:40. In one case, positivity was recorded just in the eluate. The final titres were compared in 181 paired samples of sera and eluates, all diluted at a ratio of 1:2, and it was found that the concentration of the haemagglutination-inhibition antibodies in the eluates corresponded to serum dilution ratio of 1:20. Under this assumption, the antibodies were found to have the same titre in 164 paired samples (55.8%) during the quantitative evaluation. A lower titre was recorded in 82 eluate samples (27.9%) and a higher antibody titre in 48 eluate samples (16.3%) (in comparison with the antibody titres in the respective sera). The over-all average geometrical titre (GMT) of antibodies was 1:65 in the eluates and 1:75 in the sera.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238381 TI - [The interdependence of age on the utilization of proteins and intake of fats of various quality]. AB - From an age of 30 days to 150 days, male rats were given ad libitum feed with a physiological content of nutrients (adequate to their age) and with different sources of fat: sunflower oil, pork lard, butter. The net protein ratio (NPR), body fat content, and the specific activity of phosphoenolpyruvate carboxykinase PEPCK were determined every 15 days. For all the three fat sources, NPR had the same high values in the intensive growth period (age 45 and 60 days: increased protein demand for building the organism); lower and the same again are the NPR values at an age of 75 to 105 days. From an age of 120 days to 150 days (the end of maturation), the long-continued intake of lard and butter had an adverse effect on the availability of protein for the animals, though their food had a physiological structure and an optimum proportion of the saccharide components. The result correlates with the growth of PEPCK activity, as indicated by exploitation of protein as substrate for gluconeogenesis, not for proteosynthesis. Pork lard and butter with a 3.5 - to 5-fold prevalence of saturated fatty acids, compared with sunflower oil, implies that short-chain fatty acids were provided as effectors of gluconeogenesis and that, under the conditions of physiological intake of nutrients, substrates were also provided for mitochondrial synthesis of fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238383 TI - [Pathologico-morphologic changes in the digestive system in rabid foxes]. AB - Pathologico-morphological changes in the digestive tract were investigated in fifty naturally infected common foxes (Vulpes vulpes crucigera). Nineteen animals were found to suffer from mild cachexia, 31 animals suffered from complete cachexia. Erosions were observed in the mucosa of oral cavities of 21 foxes. Traumatic injuries appeared in the teeth of 11 animals. One case of swollen and hyperaemic tongue was described; in three cases there occurred sialo-adenitis. A mild degree of inflammation was recorded in the gullet in three animals. Fifteen animals had empty stomachs, thirty-five animals had atypical food or foreign bodies in the stomach contents; simple hyperaemia was recorded 18 times, acute catarrhal gastritis 19 times and haemorrhagic gastritis was observed in two cases. Acute catarrhal enteritis was found in six cases, haemorrhagic enteritis in one case. PMID- 2238382 TI - [Evaluation of the the effectiveness of a newly developed tissue-inactivated vaccine against rabies using the NIH test]. AB - NIH test was used to verify 12 operation batches of the newly developed inactivated tissue vaccine against rabies. The number of international units per 1 cm3 of vaccine was determined by the volumetric method. The number of international units (I.U.) per 1 cm3 of the newly developed vaccines ranged from 1.08 I.U. to 2.59 I.U. per cm3. The average value of all the 12 batches tested is 1.52 I.U. per cm3. The average value of international units in the vaccination dose for dogs is 4.57. All the tested operation batches of the newly developed vaccines met the activity standard recommended by the World Health Organization for veterinary vaccines of this type. PMID- 2238384 TI - Erythrocyte pathology and mechanisms of Heinz body-mediated hemolysis in cats. AB - Despite the frequency of both oxidant drug-induced and spontaneous Heinz body formation in cats, the cellular and biochemical mechanisms by which Heinz bodies result in red blood cell (RBC) destruction and hemolytic anemia in this species remain unknown. Feline spleens are non-sinusoidal and inefficient at removing Heinz body-containing RBC from the circulation; therefore, alternative mechanisms must be involved in accelerated RBC destruction. Propylene glycol (PG) ingestion causes dose-dependent Heinz body formation and decreased RBC survival in cats. We investigated several aspects of Heinz body-containing RBC from three cats ingesting diets that provided 8.0 g PG/kg body weight for up to 3 weeks, in order to characterize cellular lesions that are associated with the presence of Heinz bodies and that might contribute to chronic, accelerated RBC destruction, as well as to gain insight into the mechanism by which PG induces Heinz body formation. Erythrocytes with PG-induced Heinz bodies had decreased levels of reduced glutathione and adenosine triphosphate and reduced deformability. There was no change in hemoglobin isoelectric focusing or membrane lipid peroxidation. Electrophoretic patterns of Heinz body-containing RBC membranes were significantly altered, and membrane surface charge distribution was disturbed. Progressively protruding Heinz bodies suggested that extrusion of Heinz bodies may be a means of cell healing and/or destruction in the absence of splenic pitting. When compared to results obtained using RBC from cats treated with the oxidant drug phenylhydrazine, significant differences were noted in packed cell volume, turbidity index, membrane heme, and morphologic appearance of Heinz bodies. Our results indicate that multiple cellular abnormalities develop in RBC with PG-induced Heinz bodies that do not cause acute hemolysis but that may shorten RBC survival. Propylene glycol-induced Heinz bodies provide an ideal model for studying the chronic effects of Heinz bodies on RBC structure and function and may be useful in understanding the mechanisms of formation and the consequences of endogenous Heinz bodies in cats. PMID- 2238385 TI - Pathologic changes of the small intestinal mucosa of pigs after feeding Phaseolus vulgaris beans. AB - The jejunal mucosa of pigs fed diets containing Phaseolus vulgaris beans was characterized grossly as mucosal atrophy and microscopically as atrophy and blunting of the villus in association with elongation of crypts with cells with increased mitotic activity. These morphologic findings were most severe in the proximal and middle parts of the jejunum. Compared to controls, goblet cells were significantly decreased in the villus but markedly increased in the crypt region. The activity of aminopeptidase and sucrase-isomaltase in the test animals was also significantly lower than in the controls. The findings in this study suggested that feeding Phaseolus vulgaris beans reduced the digestive and absorptive capacity of the mucosa, resulting in weight loss and diarrhea of affected pigs. PMID- 2238386 TI - Neosporosis in cats. AB - Six cats (Nos. 1-6) were inoculated intramuscularly with (1 x 10(6)) and orally (5 x 10(5)) tachyzoites of Neospora caninum. Three (Nos. 1-3) of the six cats were given 40 mg/kg methylprednisolone acetate 7 days before and on the day of inoculation with N. caninum tachyzoites, and three cats (Nos. 4-6) were not given methylprednisolone acetate. Two of the cats (cat Nos. 1 and 2) given methylprednisolone acetate died suddenly. Cat No. 1 died 8 days post-inoculation, and cat No. 2 died 16 days post-inoculation. Cat No. 3 was euthanatized 21 days post-inoculation. Cat No. 1 had lesions of gram-positive bacterial septicemia. Necrotizing encephalitis, myelitis, disseminated skeletal muscle necrosis, hepatic necrosis, interstitial pneumonia, and renal tubular necrosis were the main lesions in cat Nos. 2 and 3. The cats that were not given methylprednisolone acetate remained clinically normal except for slight weight loss in cat No. 6. All three of these cats were euthanatized 55 days post-inoculation. Mild myositis and encephalitis were noted on microscopic examination of tissues from these three cats. Neuromuscular lesions were not seen in six control cats (Nos. 7-12) not inoculated with N. caninum and euthanatized 21 or 22 days after administration of the first two doses of methylprednisolone acetate (40 mg/kg), given at a weekly interval. PMID- 2238387 TI - Histologic and ultrastructural studies of dermal sarcoma of walleye (Pisces: Stizostedion vitreum). AB - Sixty-seven adult walleye fish were examined by light and transmission electron microscopy. The fish were affected by a mesenchymal tumor previously termed Walleye Dermal Sarcoma that commonly affects up to 27% of the population seasonally. Biopsies from 24 fish were collected, and complete postmortem examinations were performed on 43 fish. Grossly, the tumors had the appearance of randomly distributed, often clustered, spherical nodules, 2-5 mm in diameter with a smooth and often ulcerated surface. The tumors arose from the superficial surface of scales and consisted of fibroblast-like cells separated by a moderate amount of collagen (43/67) or osteoid material (24/67). Lymphocytic infiltration (28/67) associated with vacuolar degeneration of tumor cells (28/67) and centrally located coagulation necrosis (30/67) were observed. Although tumor cells were often highly anaplastic, no local invasions or metastases were present. In contrast with previous descriptions of this tumor, no viral particles could be observed electron microscopically. The variably anaplastic appearance of the tumor, its biological behavior, and its restriction to dermis are features in common with canine cutaneous histiocytoma and equine sarcoid. The multicentric origin, the restriction to the dermis, and the absence of invasion or metastases of Walleye Dermal Sarcoma differ from retrovirus-induced avian and murine sarcomas that arise locally, that invade, and that often metastasize. PMID- 2238388 TI - Bovine fetal encephalitis and myocarditis associated with protozoal infections. AB - Bovine fetuses submitted to the California Veterinary Diagnostic Laboratory System were evaluated during a 2-year period (1987 to 1989) for the presence of multifocal necrotizing nonsuppurative encephalitis, nonsuppurative myocarditis, or tissue protozoa. Eighty-two of 445 (18%) fetuses submitted met these histologic criteria. Fetuses were from 54 dairy and two beef herds located throughout the state. In 17 fetuses (21%) protozoa were found in fetal tissues. Protozoa were found in brain parenchyma of ten fetuses (12%), in endothelial cells in four fetuses (5%), in cardiac myofibers in one fetus (1%), and were associated with endothelial cells in two fetuses (2%). In most fetuses there were no significant gross pathologic findings other than autolysis. While aborted fetuses were from 3 to 9 months gestation, the majority were between 5 and 7 months gestation. They were submitted year round, but more were seen in the fall and winter months. Additional salient histologic features included portal nonsuppurative hepatitis, focal hepatic inflammation and necrosis, and focal nonsuppurative myositis. Nonsuppurative inflammation was also found in decreasing frequency, in the adrenal medulla, kidney, mesentery or abdominal fat, placenta, and lung. In two fetuses (Nos. 1 and 2), the location and morphology of the protozoa were compatible with Sarcocystis spp. The identity of protozoa in the remaining 15 fetuses is unknown. The histopathologic changes in these 82 fetuses and the presence of protozoa in 21% of the fetuses suggest these abortions are due to fetal protozoal infections. PMID- 2238389 TI - Genetic regulation of Mycobacterium paratuberculosis infection in recombinant inbred mice. PMID- 2238390 TI - A congenital interstitial cell hamartoma of the equine ovary. PMID- 2238391 TI - Diffuse cutaneous mastocytosis in a cat. PMID- 2238392 TI - Comparison of meningio-angiomatosis in a man and a dog. PMID- 2238393 TI - Islet cell hyperplasia in an aged spider monkey (Ateles paniscus). PMID- 2238394 TI - Immunohistochemistry and ultrastructure of intestinal ganglioneuroma in a dog. PMID- 2238395 TI - Vets in society--an expanding role. PMID- 2238396 TI - Wooldridge memorial lecture. The role of vets in society. PMID- 2238397 TI - The DairyCHAMP program: a computerised recording system for dairy herds. AB - The DairyCHAMP program is an animal health and management software program that helps daily animal management, herd performance monitoring and problem analysis. Data entry to the program uses a data dictionary and includes an error-checking system that ensures the consistency and appropriateness of data entered. DairyCHAMP performs health management functions, provides a convenient user interface, ensures uniform data across farms by using a standard data dictionary, can be fully integrated with decision-making software programs like DairyORACLE, and is flexible enough to be useful for many types of dairy facilities. Data are entered via a menu-based system. Animal events are organised around reproduction and lactation cycles and health records. Farm records include inventories for drug, feed and semen. Farm parameters can be established which customize the program for an individual farm. The database system is an integration of three schemas: the individual user's view, the community view and the storage system. The individual user's view must be easy to use, while the storage system must be compact enough to fit within the disc storage space on a microcomputer. This conflict requires a translation from one schema to another. The DairyCHAMP program accomplishes this through a coding system which assigns a code number to each event. The program can add synonyms to this event dictionary by assigning the same code number to the synonym the user chooses. The DairyCHAMP program provides access to the large amounts of data required to aid in daily animal management, allow performance monitoring and analyse problems. Its highly integrated system is efficient and easy to use and maintain. PMID- 2238398 TI - 'Jackson's ratio' and the Aldabra giant tortoise (Geochelone gigantea). PMID- 2238399 TI - Phocid distemper virus--a threat to terrestrial mammals? PMID- 2238400 TI - Employing staff: perils and pitfalls. PMID- 2238401 TI - Dystocia in Friesian heifers. PMID- 2238402 TI - Wool slip in Wiltshire horns. PMID- 2238403 TI - Use of leeches. PMID- 2238404 TI - Juvenile bovine angiomatosis: a syndrome of young cattle. AB - This report describes the clinical and pathological features associated with angiomatous lesions in two calves. In the first case, a single mass located in the atrioventricular ring of the heart was responsible for congestive cardiac failure. The mass was composed of numerous vascular cavities filled with blood and lined by a single layer of well differentiated endothelial cells. The second case had multiple blood-filled cutaneous masses which were confirmed as benign vascular tumours by histological examination of a biopsy specimen. The calf was later euthanased after profuse and uncontrollable haemorrhage from one of the lesions. At necropsy, additional tumours were found in the liver, spleen, kidneys, spinal canal and attached to the pleura, omentum and mesentery. It is proposed that these two cases are representatives of solitary and multiple forms of a syndrome which should be called juvenile bovine angiomatosis. PMID- 2238405 TI - Causes of mortality in impala (Aepyceros melampus) on 20 game farms in Zimbabwe. AB - The most common cause of death in impala (Aepyceros melampus) herds on 20 game farms in Zimbabwe was stress or physical injury during capture. Acute fascioliasis due to Fasciola gigantica was identified as the main disease problem associated with smaller game farms and where impala had been recently introduced. Losses associated with ticks and tick-borne diseases were rare. Impala in Zimbabwe are maintained in a healthy condition on game farms where they are given supplementary feed during the dry winter. PMID- 2238406 TI - Reduction in UK warble infestation levels: serological survey, 1990. PMID- 2238407 TI - Pulmonary epidermoid cysts in a cat. PMID- 2238408 TI - Gastric dilatation in a bulldog. PMID- 2238409 TI - Pet health insurance. PMID- 2238410 TI - Suspected poisoning of cats. PMID- 2238411 TI - Disease in young pheasants. PMID- 2238412 TI - Strength of bones in chickens. PMID- 2238413 TI - Efficacy of ivermectin against benzimidazole-resistant nematodes of sheep. AB - Two trials involving a total of 36 Dorset horn lambs were conducted to assess the anthelmintic efficacy of ivermectin against experimental infections of benzimidazole-resistant strains of Haemonchus contortus and Ostertagia circumcincta. Two resistant strains of each of the two species were used and in each trial the lambs were allocated to three groups. One group was given 200 micrograms ivermectin/kg bodyweight orally, the second group was given 5 mg oxfendazole/kg bodyweight orally and the third group remained untreated as controls. Fourteen days after treatment the lambs were necropsied. Ivermectin was found to be more than 99 per cent to 100 per cent effective against all four benzimidazole-resistant strains, whereas oxfendazole was 78.6 per cent and 83.8 per cent effective against the H contortus strains, and 25.6 per cent and 39.8 per cent effective against the O circumcincta strains. PMID- 2238414 TI - Holoacardius amorphus totalis in two Friesian cows carrying natural and induced twins. AB - Two cases of holoacardius amorphus totalis are described and the classification, epidemiology, aetiology and pathophysiology of the condition are reviewed. One case is the first reported example of holoacardius amorphus totalis in a dairy cow carrying twins induced by embryo transfer. PMID- 2238415 TI - Isolation of peste des petits ruminants from goats in Saudi Arabia. PMID- 2238416 TI - Quality assurance in private veterinary laboratories. PMID- 2238418 TI - Lead contaminated cattle feed. PMID- 2238417 TI - Enterohaemolysin and shiga-like toxin genes in E coli. PMID- 2238419 TI - Side effects of indomethacin in ponies. PMID- 2238420 TI - International disease surveillance. Quarterly report April to July 1990. PMID- 2238421 TI - Concurrent maedi-visna virus infection and pulmonary adenomatosis in a commercial breeding flock in East Anglia. AB - The seroprevalence of maedi-visna virus infection in thin potential cull ewes aged over two years in a flock in East Anglia increased from 3.7 per cent in August 1985 to 39.0 per cent in September 1987 and 93.3 per cent in May 1989. This increase coincided with the first appearance of sheep pulmonary adenomatosis in the flock. Four emaciated ewes which were dyspnoeic were necropsied between 1987 and 1989. Maedi and pulmonary adenomatosis were confirmed histologically in one of these ewes and pulmonary adenomatosis was confirmed in the other three. PMID- 2238422 TI - 1;16 tandem translocation with trisomy 16 in a Brown Swiss bull. PMID- 2238423 TI - An outbreak of botulism type B in horses. PMID- 2238424 TI - Dystocia in Friesian heifers. PMID- 2238425 TI - Strength of bones in chickens. PMID- 2238426 TI - Equine tapeworms more prevalent. PMID- 2238427 TI - Diagnosis of bovine cryptosporidiosis by an enzyme-linked immunosorbent assay. AB - This paper describes an enzyme-linked immunosorbent assay (ELISA) for the diagnosis of cryptosporidiosis. A monoclonal antibody with a high affinity against an oocyst antigen was used to set up the test. The efficiency of this assay was compared with that of the flotation test; 275 calf faecal samples were examined by the two methods. There was 96% agreement between the two tests. For the 11 conflicting samples, the two tests were repeated and a modified Ziehl Neelsen staining was performed on faecal smears. All these 11 samples contained few oocysts, but only five and six of them were shown to be positive by the ELISA and flotation tests, respectively. The degree of sensitivity of the ELISA and flotation tests is comparable; samples heavily or moderately contaminated with oocytes are detected by both methods. This ELISA is reliable and never gives rise to false positive results. Nevertheless, as with the flotation test, the occasional case containing very few oocysts will not always be detected by this test. If necessary, very accurate diagnosis can be made by a staining technique or by a direct immunofluorescent assay. In veterinary medicine, the ELISA seems to be a method of choice; it appears to be a fast and reliable technique which could be used as a routine test for the detection of Cryptosporidium oocysts. Nevertheless the degree of sensitivity must always be borne in mind. There is no need for a microscopic examination, which is an additional advantage. PMID- 2238428 TI - Effects of multiple dose infections with Ascaris suum on blood gastrointestinal hormone levels in pigs. AB - Ten consecutive daily doses of infective Ascaris suum eggs were administered to pigs in two experiments and the levels of gastrointestinal hormones in their blood were measured. The piglets in each experiment were divided into low-dose (LDI) and high-dose (HDI) infections and control groups. Infected pigs had lower feed consumption, lower weight gains, and lower feed efficiency than control pigs. Serum gastrin levels in infected pigs were significantly lower than the controls from Days 7 to 17 post first inoculation (PFI), and so were their serum glucagon levels from Days 12 to 24 PFI. Serum insulin levels in infected animals were sometimes lower than those in controls. These differences were usually more intense in the LDI pigs than in HDI pigs. The plasma cholecystokinin (CCK) levels in the LDI group were significantly higher than those in controls from Day 10 PFI to the end of the experiment, while the CCK levels in the HDI group did not differ significantly from the controls. Increased plasma CCK levels could be a satiety factor in A. suum infection since the time of occurrence of high levels of CCK matched the period of reduced feed consumption. PMID- 2238429 TI - The seasonal epidemiology of gastrointestinal nematodes in N'Dama cattle in The Gambia. AB - From June 1987 to June 1988, a total of 180 N'Dama cattle were necropsied to identify and enumerate parasites present, including 39 sick calves and 25 dead calves from local village herds, and 116 adult cattle from a local abattoir. Of 175 animals infected with one or more helminths (97%), Haemonchus contortus was found in 67% of all necropsied animals, Cooperia punctata in 75%, Cooperia pectinata in 55%, Oesophagostomum radiatum in 71% and Bunostomum phlebotomum in 21%. There was a wide range of worm burdens (0-22 925) and a pronounced seasonal pattern occurred. Eighty-two percent of the total adult Haemonchus burden occurred during the rainy season (June-October). By the end of the rainy season, almost 100% of the Haemonchus burden was present as inhibited larvae. By contrast, a different survival strategy appeared to occur in Cooperia spp.; Oesophagostomum spp. and Bunostomum spp., which were found as adults throughout the year. Results indicated that, apart from malnutrition during the dry season, gastrointestinal nematode infections, especially haemonchosis, represent a major constraint on the health and productivity of N'Dama cattle under West African savanna conditions. PMID- 2238430 TI - Absence of hypobiosis in abomasal nematodes of sheep and goats in Egypt. AB - A total of 96 abomasa from sheep and goats at the Zagazig abattoir, Sharkia Province, Egypt, were examined, during the four climatic seasons from April 1986 to March 1987, for the presence of adult and larval nematodes. Adults of Trichostrongylus axei were most numerous followed by adult Haemonchus contortus. Adult Ostertagia sp. and Parabronema skrjabini were less prevalent. There was no significant difference between sheep and goats in infection rates, but worm burdens of the nematodes other than Ostertagia sp. were significantly higher (P less than 0.05) in sheep than in goats. The animals were uniformly infected with these parasites throughout the year as there were no significant differences in the incidence or intensity of infections between the four seasons. The numbers of larvae recovered from the wall of the abomasa were small in relation to the total adult worm population throughout the year with a slight increase during the summer. Hypobiosis, therefore, seems not to be important in the life cycle of abomasal nematodes of sheep and goats in Sharkia Province, Egypt. PMID- 2238432 TI - Eimeria infections of sheep in northwest Germany. AB - To investigate the incidence of ovine Eimeria spp. and seasonal dynamics in oocyst output, fecal samples of sheep from three different management systems were collected monthly over a 1-year period and examined for oocysts. A total of 10 species of Eimeria were observed. The most frequent species were E. bakuensis, E. ovinoidalis, E. weybridgensis/crandallis, E. parva and E. ahsata whereas E. faurei, E. granulosa, E. intricata and E. pallida were found less often. Lambs passed larger numbers of oocysts in their feces than either ewes or yearlings. PMID- 2238431 TI - Is there a relationship between haemoglobin genotype and the innate resistance to experimental Haemonchus contortus infection in Merino lambs? AB - Responses to a single or repeated infection with 7000 infective larvae of Haemonchus contortus were studied in an experiment using a total of 106 3-month old lambs with AA, AB or BB haemoglobin (Hb) genotypes. Results were assessed by faecal egg counts, adult worm counts, haematocrit values, haemoglobin concentrations, total serum protein and serum antibody IgG1 and IgA ELISA titres. None of these parameters showed a strong relationship to the Hb type. The prevalence of low responder (greater than 500 worms) and of high responder (less than 50 worms) animals in groups AA, AB and BB Hb types was 3.8 and 34.6, 20.6 and 35.2, 28.1 and 43.7%, respectively, suggesting that the responsiveness to nematode infection is under the control of gene(s) not closely linked with those determining the Hb genotype. Worm counts of a primary infection are more subject to variation than those of a secondary infection. There is a strong relationship between adult worm counts and faecal egg counts taken close to the time of slaughter. In living animals low and high responder discrimination can be based on individual faecal egg counts around 50 days after a secondary infection. Haematocrit values proved to be of little value in the low and high responder selection. In this regard neither Hb concentration nor total serum protein values are of practical significance. In 3-month-old lambs primary infection induced partial immunity which could prevent the establishment of a part of the secondary infection, irrespective of the presence or absence of the primary worm population. The development of immunity was not associated with an increase of serum IgG1 and IgA antibody levels. Specific antibody production was not influenced by Hb types. Mean antibody levels of low responder lambs showed no difference from those of high responders. Thus, serum IgG1 and IgA levels are of no predictive value in identifying lambs which are genetically resistant to Haemonchus infection. PMID- 2238433 TI - Effects of the combination of DL-alpha-difluoromethylornithine and diminazene aceturate in Trypanosoma congolense infection of dogs. AB - The therapeutic activity of a combination of difluoromethylornithine (DFMO) with diminazene aceturate was investigated in mongrel dogs experimentally infected with Trypanosoma congolense. The criteria used in the assessment of the trypanocidal effect of the therapy include the examination of the blood for parasites, as well as clinical and haematological changes at intervals following treatment. Diminazene aceturate and DFMO alone and in combination produced intermittent aparasitaemia in the dogs. Although relapse infection occurred with all three treatment regimes, the drug combination gave the best result. The packed red cell volume, haemoglobin concentrations and red blood cell values decreased significantly following parasite inoculation but increased after treatment. The total leucocyte counts decreased in all the infected dogs but improved with treatment, and the differential leucocyte counts indicated neutropenia in all the infected animals prior to treatment. PMID- 2238434 TI - Cantharidin decreases in vitro digestion of alfalfa and smooth bromegrass. AB - Blister beetles (Coleoptera:Meloidae) containing the toxin cantharidin can be incorporated with alfalfa (Medicago sativa L) during forage conservation. Cantharidin inadvertently ingested with animal feed may cause illness or death. Little information is available on the effects of cantharidin on ruminant microbial digestion. The objective of our study was to determine cantharidin effects on digestibility of alfalfa and smooth bromegrass (Bromus inermis Leyss) by measuring in vitro digestible dry matter (IVDDM) and cell wall digestion (CWD). Alfalfa dry matter digestibility, measured after IVDDM at 48 and 96 h fermentation periods, decreased as cantharidin concentration increased. Increasing cantharidin concentration also significantly reduced IVDDM of smooth bromegrass at 24 and 96 h digestion time. The CWD of alfalfa and smooth bromegrass decreased as cantharidin concentration increased. These results indicate that ingestion of cantharidin by ruminants may decrease microbial digestion of fibrous feeds and therefore may decrease the efficiency of feed utilization by ruminants. PMID- 2238435 TI - The effect of testosterone or estradiol on the development of TOCP-induced delayed neurotoxicity in immature broiler-breed cockerels. AB - Immature cockerels were susceptible to OPIDN when dosed with TOCP. Using 30 broiler-breed cockerels, 6 w old, 10 birds each received 28 daily im injections of either 50 mg estradiol, 100 mg testosterone or 0.1 ml of vehicle. At 7 w of age, 5 birds in each of the 3 groups received a single oral dose of 500 mg TOCP/kg body weight, while the remaining 5 birds/groups were given corn oil. The birds were observed daily for 14 d beginning on day 8 post-TOCP exposure for the development of clinical signs characteristic of OPIDN. At 21 d post-TOCP, all birds were killed and the adrenal gland and testes were prepared for histopathology of the birds that received TOCP, 1 of 5 that were given testosterone and 2 of 5 that received estradiol had signs typical of OPIDN. All of the 5 birds that received TOCP alone showed OPIDN signs. The testes of the TOCP-exposed birds that showed clinical signs had reductions in the size of the seminiferous tubules and no evidence of spermatogenic activity. This study demonstrated that sex hormones can modulate the clinical effects of TOCP in immature cockerels through unknown mechanisms that are similar to those reported for corticosterone in adult chickens. PMID- 2238436 TI - Oral forms of the oxime HI-6: a study of pharmacokinetics and tolerance after administration to healthy volunteers. AB - New pharmaceutical formulations of the oxime HI-6 as sustained-release and conventional tablets were studied in healthy volunteers. Twenty-six subjects, divided into 3 groups, received 3784 mg or 7568 mg doses of HI-6 conventional tablets or 4027 mg of the oxime in the form of sustained-release tablets. Peak plasma concentrations of HI-6 were reached within 0.6 h (10.2 mumol/l) and 1.6 h (21.4 mumol/l) following the ingestion of conventional tablets. Elimination half lives were similar (1.7 h and 1.3 h) and the respective urinary recoveries amounted to 3.2% and 2.9%. After the administration of sustained-release tablets of HI-6, maximal concentration (8.8 mumol/l) was attained in 2.2 h, elimination half-life was 1.9 h and 4.2% of the dose was excreted unchanged in urine. Undesirable side effects were not reported by the subjects or revealed by clinical or laboratory tests. The results indicate low bioavailability of the oral formulations of HI-6 in man. PMID- 2238437 TI - Study of delayed neurotoxicity caused by fatty acid anilides in hens. AB - We have observed that the oral administration of a single dose of a mixture of oleyl and linoleylanilides (80 mg/kg) in adult hens determines the apparition of delayed muscular neuropathy, which we have compared to that induced by metamidophos as a model of organophosphate-induced delayed neuropathy (OPIDN). We have compared the modifications produced by each of the 2 treatments on the enzymatic activity of neuropathy target esterase (NTE) measured in nervous tissue homogenates of brain, medulla and sciatic nerve. In addition we determined total esterases (TE), acetylcholine esterase (AchE) and serum creatine phosphate kinase (CPK). The organophosphate compound (OP) induced an initial reduction in the activity of NTE, TE and AchE which was reestablished 48 h later, except for brain TE which increased slowly during the latency period. This behaviour was accompanied by a permanent increase in the activity of serum CPK. Anilides induced a strong activation of AchE, NTE and TE (except brain TE) in the first 24 36 h. Normal levels were relatively quickly reestablished in brain (by 48 h) and slowly in medulla and sciatic nerve. But the AchE activity remained high throughout the whole period of latency. This activity level coincided with the AchE level observed at the onset of signs in animals dosed with OPs. CPK was also increased in sciatic nerve at 15 d but was depressed in serum throughout the whole latency period. Substances with chemical characteristics very different from OPs can induce a delayed neuropathy with modification of the activity of NTE. PMID- 2238438 TI - Evaluation of potential antidotes for sodium fluoroacetate in mice. AB - Pathogenesis in fluoroacetate poisoning is multifactorial. Biochemically it is characterized by lethal synthesis of fluorocitrate, causing hypocalcemia, and energy deficiency through blockade of the TCA cycle. Calcium gluconate (CaG) was chosen to antagonize hypocalcemia, while sodium alpha kelogluterate (NaKG) and sodium succinate (NaSuc) were selected as potential antidotes to revive the TCA cycle. Effectiveness of each of these antidotes individually and in certain combinations was tested in mice exposed to lethal doses (15 mg/kg ip) of sodium fluoroacetate (NaFAC). Antidotal treatments were administered at 15 min, 4 h, 10 h, 24 h, and 36 h after NaFAC. All 3 of the antidotes alone, as well as a combination of CaG with NaKG, were ineffective in reducing mortality in mice after NaFAC. On the other hand, a combination of CaG (130 mg/kg) with NaSuc (240 mg/kg) was effective if the 2 solutions were either injected at separate sites or mixed in the same syringe just prior to injection. Similar solutions, if mixed for 24 h or longer before administrations, were ineffective. Increasing the dose of NaSuc to 360 or 480 mg/kg with CaG (130 mg/kg) was unrewarding. These results indicate that CaG in combination with 240 mg NaSuc/kg offer a promising therapy modality in NaFAC intoxication. Additional studies involving biochemical parameters and other species are needed to confirm the efficacy and mechanism(s) of action of this combination. PMID- 2238439 TI - Dermal toxicity to rats of isoproturon technical and formulation. AB - Information on the toxicity of urea-based herbicides is meagre and no data are available on the subacute dermal toxicity of isoproturon and its formulation. Repeated applications of isoproturon technical (IPT) and its wettable powder formulation (IPF) to the skin of male and female rats for 21 days caused mild to moderate toxic effects. IPT was more toxic to male rats as evidenced by animal mortality and enzymatic and hematological changes. The toxicity of IPF was less to both sexes. No dose response relationship could be established since the enzymatic and hematological changes produced by 3 different dose levels were equal. PMID- 2238440 TI - In vitro modifications of rat NTE and other esterases by chemicals which induce delayed neurotoxicity in vivo. AB - A rat in vitro model has been developed which permits direct study of the biochemical mechanisms involved in delayed neurotoxicity induced by any chemical compound, not only organophosphates. Using rat brain homogenate, a parallel study on the activity of neurotoxic esterase (NTE) and total esterases (TE) compared the action of metamidophos, which is known to induce delayed neurotoxicity, and the synthetic fatty acid anilides, oleylanilide and linoleylanilide. Inhibition in the activity of NTE and TE, unrelated to the concentration and the incubation time assayed, was caused by metamidophos, while the anilides showed a 2-phase concentration-time dependent behaviour. This confirmed the results we previously obtained in vivo. In both cases the appearance of delayed neuropathy was related to modification of NTE activity. We concluded that phosphorylation of the enzyme may not be the only biochemical requirement for the development of delayed neurotoxicity syndromes in which modification of NTE is produced. PMID- 2238441 TI - Mojave rattlesnake (Crotalus scutulatus scutulatus) venom: in vitro effect on platelets, fibrinolysis, and fibrinogen clotting. AB - Rattlesnake envenomation commonly produce defects in the hemostatic mechanism. However, Mojave rattlesnake (Crotalus scutulatus scutulatus) envenomation has been reported not to cause a systemic bleeding diathesis. In this study, whole venom from the Mojave rattlesnake was tested in vitro for fibrinogen clotting activity, ability to induce platelet aggregation, and for fibrinolytic activity. The Mojave venom caused no fibrinogen clotting and it displayed very weak ability to cause platelet aggregation and fibrinolytic activity. These in vitro studies support the clinical observation that Mojave envenomation does not cause a coagulopathy. PMID- 2238442 TI - Signal grass (Brachiaria decumbens) toxicity in sheep: changes in rumen microbial populations and volatile fatty acid concentrations. AB - Brachiaria decumbens toxicity resulted in an altered reticulorumen environment in the sheep. This adversely affected the growth and activity of microorganisms in the rumen as reflected by greatly decreased concentrations of the volatile fatty acids (acetic, propionic and butyric) in B decumbens-intoxicated sheep. PMID- 2238443 TI - Xylene/amitraz: a pharmacologic review and profile. AB - There are no reports of xylene/amitraz ingestion in children. Studies have characterized the adverse reactions caused by dermal applications in dogs, but the mechanisms involved were undetermined Accidental ingestion of the product by a child prompted a retrospective search of the medical records of the Georgia Animal Poison Information Center to profile the signalment, clinical signs, route of exposure and target sites of the suspected toxicosis in dogs. Clinical signs of depression, ataxia, stupor, and coma were most attributable to the xylene and propylene oxide components. Hyperglycemia, hypotension, and bradycardia were probably attributable to the alpha-2 adrenoceptor agonist action of amitraz. Most reports were initiated by owners, using the prescription product at home. PMID- 2238444 TI - A review of carboxymyoglobin formation: a major mechanism of carbon monoxide toxicity. AB - Clinical data suggest, and experimental studies indicate direct cardiotoxic effects of carbon monoxide, apart from carboxyhemoglobin formation. Carbon monoxide interactions with cytochrome oxidase and myoglobin are suspect. Of these, myoglobin is the favored tissue target for carbon monoxide binding. On what evidence? Examination of the literature reveals the following: A 16% greater "volume of distribution" (Vd) for carbon monoxide, versus other blood volume indicators, concentrating in skeletal and cardiac muscle; A high myoglobin content in these tissues corresponding to this "excess" Vd for carbon monoxide; Evidence from animals of significant carboxymyoglobin concentrations; Hemeprotein independent changes produced by carbon monoxide which promote carbon monoxide myoglobin interactions; A high ratio of deoxymyoglobin (carbon monoxide binding form) to oxymyoglobin intracellularly; Direct intercellular measurements of oxymyoglobin saturations and "cycling" in vivo illustrating favorable conditions for carbon monoxide binding; Data indicating decrements in cardiac performance with loss of functional myoglobin; Evidence that myoglobin is important to the proper functioning of cardio-adaptive mechanisms in stress. The total picture of carbon monoxide poisoning must take into account pathogenic effects due to carboxymyoglobin formation. PMID- 2238445 TI - The lead content of plants and animals as indicators of environmental contamination. AB - Lead content of tissues from some edible plants, pigeons and a vulture, and from human and cattle blood were determined to gain insight into the extent of environmental lead contamination in Zaria and Kaduna environs of Kaduna state of Nigeria. The results suggest that environmental lead contamination in these areas was insignificant when compared to values from developed countries like US. However, there is need for more work of this nature on a regional basis to ascertain the true picture of total environmental lead pollution in Nigeria. PMID- 2238446 TI - A review on biochemical roles, toxicity and interactions of zinc, copper and iron: IV. Interactions. AB - While the major impetus of most of our present knowledge of these metals emphasizes their deficiencies or toxicities, little has been done on their metabolic interactions. Such interactions acknowledge the importance of nutritional deficiencies or toxicities in the biospheres. The effect of dietary zinc supplementation on the bioavailability of copper and iron is a matter of conjecture. Likewise, further research is needed before a unifying hypothesis can be established on the effect of imbalances or interactions among copper and iron. Such mineral imbalance studies will be of value in determining their dietary requirements and in appraising circumstances in which risk to human and animal health may arise. PMID- 2238447 TI - Research note: an inexpensive temporary incubator conversion for submerged organ culture. PMID- 2238448 TI - Button batteries: letting the skeleton out of our closet. PMID- 2238449 TI - Fatal poisoning by Rumex crispus (curled dock): pathological findings and application of scanning electron microscopy. AB - A case of fatal poisoning due to ingestion of the plant Rumex crispus (curled dock) is described. The patient, a 53-year-old male, presented with gastrointestinal symptoms, severe hypocalcemia, metabolic acidosis and acute hepatic insufficiency. Despite therapeutic measures, the patient died 72 h after ingestion of the plant material. Noteworthy among the pathological findings were centrolobular hepatic necrosis and birefringent crystals in the liver and kidneys that were identified by histochemical techniques and scanning electron microscopy. These observations are compared with other reports in the medical literature, with an emphasis on the risk involved in the use of these plants for culinary or medicinal purposes. PMID- 2238450 TI - Publication of presented abstracts at annual scientific meetings: a measure of quality? AB - One measure of the quality of research presented at the annual scientific meeting is publication of the data presented in a peer review journal. This allows for a more rigorous review of design, methodology and conclusions. To determine the rate of subsequent publication, MEDLARS searches were performed on the 269 presented abstracts at the 1984 and 1986 meetings of the American Association of Poison Control Centers, The American Academy of Clinical Toxicology, The American Board of Medical Toxicology and the Canadian Association of Poison Control Centers. Of the 296 presented abstracts, 134 (49.8%) were published. There was no difference in the eventual publication rate between the 1984 and 1986 meeting. There were 38 non-reviewed symposia publications and 96 peer-reviewed articles. Publications of 35.7% of presented abstracts in peer review journals compares poorly with the percentage of peer-reviewed publication from other scientific meetings. If publication in a peer-review journal is important, steps should be taken to improve the percentage of presented abstracts that are accepted by peer review journals. PMID- 2238451 TI - Species differences: the applicability of data from one animal model to another. PMID- 2238452 TI - Incidence and management of poisonings in livestock. AB - Insecticides, nitrates, gossypol, copper, and plants are a few of the common toxicoses observed in livestock in a particular specie due to various factors. Some species may have anatomical or physiological uniquenesses making them more susceptible to certain agents. Another specie may be exposed to some agents more frequently than others, increasing the likelihood of toxicosis in that specie. Once recognized, therapy is often unrewarding due to the advanced stage of the condition when first recognized, the stress involved in administering the treatment, and the unfeasibility of multiple treatments on many animals. Because of the poor response to treatment and the large number of animals potentially at risk, prevention assumes a greater importance in food animals than in companion animals. Prevention consists of making the diagnosis, findings and removing the source of the toxicant, and educating the owner on how future problems can be avoided. PMID- 2238453 TI - Incidence and management of poisoning in companion animals. PMID- 2238454 TI - Human effects of veterinary biological products. PMID- 2238455 TI - Nitrate intoxication. PMID- 2238456 TI - Isolation and restriction endonuclease analysis of a tetracycline resistance plasmid from Staphylococcus hyicus. AB - A plasmid of 4.550 kb, conferring resistance to tetracycline, was demonstrated in Staphylococcus hyicus cultures from piglets with exudative epidermidis. The plasmid-encoded properties were determined both by curing and interspecific protoplast transformation experiments. The tetracycline resistance (TET) plasmid, designated pST1, was characterized by restriction endonuclease analysis and a preliminary restriction map was constructed. The pST1 plasmid was demonstrated in 19 (57.6%) of 33 S. hyicus cultures by Southern blot hybridization. It was also detectable by electron microscopy. PMID- 2238457 TI - Slide precipitation: a simple method to type Actinobacillus (Haemophilus) pleuropneumoniae. AB - Soluble thermostable antigens prepared from Actinobacillus pleuropneumoniae, as commonly applied in the ring precipitation test, were used in rapid slide tests. This method was easier to perform than the ring precipitation test and showed the same specificity. This specificity was higher than that obtained in slide agglutination tests using whole bacterial cells. PMID- 2238458 TI - Detection of Eperythrozoon suis DNA from swine blood by whole organism DNA hybridizations. AB - A procedure is described for isolating Eperythrozoon suis DNA of sufficient quantity and purity to serve as a probe in whole-organism DNA hybridizations for detecting parasitized swine. The E. suis organisms were isolated from the blood of infected swine; the DNA was recovered and digested with restriction endonucleases and resolved on agarose gels. In DNA hybridizations using recovered E. suis DNA, blood samples from parasitized swine could be differentiated from uninfected, control samples. A high salt lysate recovery technique was used in sampling swine whole blood for E. suis DNA and found to offer many advantages in the collection and recovery process. PMID- 2238459 TI - The growth response of Mycoplasma hyopneumoniae and Mycoplasma flocculare based upon ATP-dependent luminometry. AB - Cultures of Mycoplasma hyopneumoniae and M. flocculare in Friis' broth grew faster and to higher titers in air than in 8% CO2; cultures in air grew better when shaken than when stationary. Under the optimal conditions, both species have generation times of about 10 h and achieve maximum titers of at least 10(9) organisms per ml. Maximum growth was reached near pH 7.0, before the phenol red indicator had noticeably changed colour. Changes in growth were readily detected by an ATP assay based upon the luciferin-luciferase reaction. Concentrations of ATP fell rapidly after peak growth. Although the addition of 27 mM glucose to the medium did not change the pattern of growth and gas chromatography gave no evidence of the production of volatile or non-volatile end-products, washed harvested cells of both species metabolized [14C]-glucose. The addition of 29 mM arginine to the medium inhibited growth. PMID- 2238460 TI - The humoral immune response of lambs experimentally infected with Mycoplasma ovipneumoniae. AB - Using sera from lambs experimentally infected with Mycoplasma ovipneumoniae and Pasteurella haemolytica, the development of a good humoral immune response to M. ovipneumoniae was detected by ELISA. The antibody titres peaked 41 days post infection and good antibody titres were maintained over the 16-week experimental period. Immunoblotting revealed that antibodies to specific antigens appeared in the sera in a sequential manner, some being seen shortly after infection and others developing only after a substantial time lag. Antibodies were raised against almost all the major antigens detected in one laboratory strain (956/2) and against all antigens previously shown to be conserved in 22 Scottish field isolates of M. ovipneumoniae. PMID- 2238461 TI - The development and evaluation of an enzyme-linked immunosorbent assay for the detection of Mycobacterium bovis. AB - A double antibody sandwich layer enzyme-linked immunosorbent assay (ELISA) was used to detect Mycobacterium bovis. The ELISA detected M. bovis is pure culture at concentrations of 1 x 10(5) colony-forming units (CFU) ml-1 and greater, compared to a minimum detection level of 1 x 10(6) CFU ml-1 for isolation techniques. Neither technique detected M. bovis at 1 x 10(4) CFU ml-1. The ELISA did not cross-react with common mycobacterial contaminants such as Mycobacterium avium intracellulare-scrofulaceum complex serotypes 18 and 42, M. terrae, M. fortuitum, M. flavescens and with Escherichia coli or Rhodococcus equi. Further work is needed to evaluate this assay in detecting M. bovis in tissues and the environment. PMID- 2238463 TI - Control and expression of 3' open reading frames in clover yellow mosaic virus. AB - The genomic RNA of clover yellow mosaic virus (CYMV) contains at least seven open reading frames (ORFs) which are organized in a more elaborate array than in other sequenced members of the potexvirus group. We have investigated the strategy by which ORFs located in the 3' region of CYMV's genomic RNA are differentially expressed by correlating the location of the 5' termini of the two abundant viral subgenomic RNAs with their coding potential. We have mapped the 5' termini of the subgenomic RNAs precisely to the nucleotide level and have shown that both are capped. The larger 2.1-kb subgenomic RNA encodes as its 5' ORF a 25-kDa polypeptide, whose function is unknown. The smaller 1.0-kb subgenomic RNA can encode only the 23-kDa coat protein. All four ORFs in the 3' 1095 residues of CYMV are efficiently expressed in vitro, but of these only coat protein, which can be expressed from a subgenomic RNA, is detectable in CYMV infected tissue. For this reason, we believe that expression of ORFs in the 3' one-third of CYMV RNA are controlled at the transcriptional level. PMID- 2238462 TI - Replication of an adenovirus type 34 mutant DNA containing tandem reiterations of the inverted terminal repeat. AB - A mutant of human adenovirus type 34 (Ad34) has been isolated which contains DNA molecules with tandem reiterations of from two to eight copies of a 131-bp sequence within the right-sided inverted terminal repetition. Terminal heterogeneity was not eliminated by repeated plaque purifications indicating that the population of DNA molecules with various numbers of reiterations could rapidly evolve from the DNA of a single virus particle. These enlarged DNA molecules were capable of replication both in vivo and in vitro. The nucleotide sequence of the mutant Ad34 inverted terminal repetitions contained most of the essential features of the Ad origin of DNA replication. These features include the ATAATATACC sequence which is present between the highly conserved bases 9-18 in all human adenoviruses, as well as the consensus sequences for the binding of nuclear factor I and nuclear factor III. However, the reiterated sequences lacked a dG appropriately placed on the template strand to serve as a potential site for internal initiation. It appears that the rapid amplification of two to eight copies of the reiterated terminal sequences does not arise from internal initiation during replication but probably from homologous recombination. PMID- 2238464 TI - Structure-specific binding of wound tumor virus transcripts by a host factor: involvement of both terminal nucleotide domains. AB - A gel retardation assay was used to demonstrate binding of wound tumor virus transcripts by a protein component of leafhopper vector cell extracts. Comparative binding studies employing terminally modified and internally deleted transcripts established that the segment-specific inverted repeats present in the terminal domains of the viral transcripts were necessary but not sufficient for optimal binding. An additional involvement of internal sequences in either the formation or the stabilization of the binding complex was indicated. Results of competitive binding experiments confirmed the sequence- and structure-specificity of the protein-RNA interaction and revealed apparent differences in the ability of individual viral transcripts to form a stable binding complex. Possible implications of structure-specific interactions between wound tumor virus transcripts and a host component and the role of the terminal inverted repeats are discussed. PMID- 2238465 TI - Tissue-specific expression of the TMV coat protein in transgenic tobacco plants affects the level of coat protein-mediated virus protection. AB - Transgenic tobacco plants were produced that express a chimeric gene encoding the coat protein (CP) of tobacco mosaic virus (TMV) under the control of the promoter from a ribulose bisphosphate carboxylase small subunit (rbcS) gene. Plant lines expressing comparable levels of CP from the rbcS and cauliflower mosaic virus 35S promoters were compared for resistance to TMV. In whole plant assays the 35S:CP constructs gave higher resistance than the rbcS:CP constructs. On the other hand, leaf mesophyll protoplasts isolated from both plant lines were equally resistant to infection by TMV. This indicated that the difference in resistance between the lines in the whole plant assay reflects differences at the level of short- and/or long-distance spread of TMV. Therefore, we propose that the difference in tissue specific expression between the 35S and rbcS promoters accounts for greater resistance in the plant lines that express the 35S:CP chimeric genes. PMID- 2238466 TI - A single amino acid change in E3 of ts1 mutant inhibits the intracellular transport of SFV envelope protein complex. AB - At 39 degrees the envelope protein complex (E1-p62) of Semliki Forest virus mutant ts1 is arrested in the rough endoplasmic reticulum (RER). When the infected cultures are shifted to 28 degrees, the complex is transported to the cell surface. During the transport p62 is cleaved into E2 under conditions in which no virus budding takes place. We have sequenced the cDNA, which encodes the envelope proteins of ts1. Comparison with the respective wild-type nucleotide sequence shows only one nucleotide change, G----A, causing a replacement of cysteine-58 (TGC) with tyrosine (TAC) in the E3 protein of ts1. A cDNA fragment from the ts1 genome encoding the mutation in E3 was used to replace the respective fragment of prototype SFV in an eukaryotic expression vector. Intracellular arrest of envelope proteins at 39 degrees was seen in transfected BHK21 cells. A shift of the transfected cells to 28 degrees resulted in the appearance of the envelope proteins at the cell surface. We conclude that the single point mutation is solely responsible for the temperature-sensitive transport defect of ts1 envelope glycoproteins. PMID- 2238467 TI - Mutational analysis of barley stripe mosaic virus RNA beta. AB - Barley stripe mosaic virus (BSMV), the type member of the hordeivirus group, has a plus-stranded genome comprising RNA species designated alpha, beta, and gamma. Although RNA beta is essential for infection of whole plants, it is dispensable for infection of barley protoplasts. We have used a full-length cDNA clone of RNA beta from which infectious in vitro transcripts can be derived to construct a number of mutations in its four genes. Mutations introduced into the beta b, beta c, or beta d genes eliminated infectivity of the RNA. The coat protein and the RNA sequences encoding the coat protein were completely dispensable for infection of barley plants by BSMV, and no detrimental effect on systemic movement of the virus was observed. However, besides eliminating coat protein expression in vivo, mutations within the coat protein gene and the first intercistronic region affected a number of other phenotypes: (1) expression of a downstream gene (beta b), (2) stability of the genomic RNA during virus multiplication in planta, (3) the requirement for a trans-acting BSMV protein (gamma b), (4) symptomatology and disease development in infected barley plants, and (5) host range. PMID- 2238468 TI - Expression of plasmid-encoded structural proteins permits engineering of bacteriophage T4 assembly. AB - A complementation system for studying bacteriophage T4 tail assembly has been developed and used to test the effects of nonviable mutations on the function of a specific T4 tail protein, gp48. The complementation system assays the assembly function of gp48 without requiring that viable phage be produced, circumventing the operational problems of maintaining nonviable mutants of this lytic bacteriophage. The protein to be tested was preexpressed from cloned genes in a host cell prior to infection with the challenge phage. Assembly activity was assayed by monitoring the conversion of one tail assembly intermediate, the baseplate lacking gp48, into baseplates containing gp48 or into tube baseplates (or sheathed tails) assembled from such baseplates. Specific incorporation of gp48 into these structures was confirmed using gp48-specific antiserum, and the same serum was used in direct immunoelectron microscopy experiments to localize gp48 to the baseplate-proximal end of the T4 tail tube, at the site where the tube and sheath bind to the baseplate. The protein gp48 has been previously shown to be a baseplate protein, as well as a tail-tube-associated protein, and was tested for a possible role as a tail-length tape-measure protein. Tests with a deleted variant of gp48 were inconclusive because the protein was inactive. A variant of gp48, 20% longer than wild-type protein due to an internal duplication, was found to be partly functional in our assembly complementation system. This abnormally elongated protein allows several assembly steps to proceed, including the assembly of normal length T4 tails, implying that it does not specify tail length. The insertion-duplication variant of gp48 appears to have a defect in its interaction with the tail sheath protein, leading to abnormal sheath contraction. PMID- 2238469 TI - Molecular characterization of a new hemagglutinin, subtype H14, of influenza A virus. AB - Two influenza A viruses whose hemagglutinin (HA) did not react with any of the reference antisera for the 13 recognized HA subtypes were isolated from mallard ducks in the USSR. Antigenic analysis by hemagglutination inhibition and double immunodiffusion tests showed that the HAs of these viruses are similar to each other but distinct from the HAs of other influenza A viruses. Nucleotide sequence analysis showed that these HA genes differ from each other by only 21 nucleotides. However, they differ from all other HA subtypes at the amino acid level by at least 31% in HAI. Thus, we propose that the HAs of these viruses [A/Mallard/Gurjev/263/82 (H14N5) and A/Mallard/Gurjev/244/82 (H14N6) belong to a previously unrecognized subtype, and are designated H14. Unlike any other HAs of influenza viruses, the H14 HAs contained lysine at the cleavage site between HA1 and HA2 instead of arginine. Experimental infection of domestic poultry and ferrets with A/Mallard/Gurjev/263/82 (H14N5) showed that the virus is avirulent for these animals. Based on comparative sequence analysis of different HA genes, it is suggested that differences of 30% or more at the amino acid level in HA1 constitute separate subtypes. Phylogenetic analysis of representatives of each HA subtype showed that H14 is one of the most recently diverged lineages while H8 and H12 branched off early during the evolution of the HA subtypes. These latter two subtypes (H8 and H12) have been isolated very infrequently in recent years, suggesting that these old subtypes may be disappearing from the influenza reservoirs in nature. PMID- 2238470 TI - Replication of sonchus yellow net virus in infected protoplasts. AB - Tobacco (Nicotiana edwardsonii and N. benthamiana) protoplasts infected with the plant rhabdovirus sonchus yellow net virus (SYNV) were found to be suitable for studies of replication. SYNV messenger RNAs could be detected within 2 hr postinoculation (PI), accumulated to a maximum within 24 hr, and subsequently declined to undetectable levels by 60 hr. Plus- and minus-sense genomic RNAs appeared later and were most abundant by 36 hr PI, but the levels decreased by 60 hr. The four major SYNV structural proteins could be detected by Western blot serological analyses by 24 hr PI and were present in highest concentrations between 43 and 60 hr PI. Among various glycosylation inhibitors, only tunicamycin treatment of protoplasts altered viral protein patterns and resulted in synthesis of a glycoprotein with an apparent molecular weight (Mr) 10% smaller than that found in untreated protoplasts. Two specific cleavage products of the nucleocapsid protein estimated to be 21,000 and 37,000 Mr appeared in N. benthamiana-infected protoplasts by 60 hr PI, but in the presence of tunicamycin, the cleavage products were evident by 38 hr. This result suggests that specific cleavage of the N protein is correlated with stress of infected cells due to viral accumulation and/or tunicamycin treatment. PMID- 2238471 TI - Defective interfering particles: effects in modulating virus growth and persistence. AB - Defective interfering virus particles (DIP) frequently play an important part in viral persistence in vitro, and may in some instances modify a virus infection in vivo, causing attenuation or persistence of the infection. To explain certain aspects of the growth of these mutants in vitro, other factors have been invoked such as interferon, mutations in the wild-type virus or the infected cells, or other substances released by infected cells that attenuate the infection. We present here a simple model of the growth of DIP in vitro which shows that (a) the observed population dynamics of DIP can readily be explained without invoking such extrinsic factors; (b) the initial multiplicity of infection of DIP is the principal determinant of the outcome of infection in both single- and repeated passage cultures; and (c) in a long-term culture in vitro, the criterion used to decide the time of virus passage directly determines how long the standard virus, DIP, and cells survive. This model may be used with minor modifications to predict the behavior in vitro of other mutant viruses with a dominantly interfering phenotype. PMID- 2238472 TI - The human immunodeficiency virus type 1 envelope glycoprotein precursor acquires aberrant intermolecular disulfide bonds that may prevent normal proteolytic processing. AB - The envelope glycoprotein of human immunodeficiency virus consists of two subunits, designated gp120 and gp41, derived from the cleavage of a precursor polypeptide gp160. When expressed from a recombinant vaccinia virus and analyzed by velocity gradient sedimentation and polyacrylamide gel electrophoresis, a significant proportion of gp160 molecules formed oligomers that were stabilized by intermolecular disulfide bonds. Oligomeric forms of both gp120 and gp41 were also observed, but these oligomers were noncovalently associated. Both the intermolecularly linked oligomers of gp160 and the unlinked oligomeric envelope protein subunits were found to accumulate with time. These results indicate that there are two populations of gp160 precursors, one that is folded and processed correctly into gp120 and gp41 and another that is intermolecularly disulfide bonded and remains uncleaved. We propose that the formation of intermolecular disulfide bonds is not an intermediate step in the maturation of the envelope glycoprotein, but rather a result of misfolding of the gp160 precursor which prevents it from being properly processed. PMID- 2238473 TI - Reovirus RNA is infectious. AB - Conditions under which reovirus RNA is infectious have been worked out. In brief, single-stranded (plus-stranded, ss) and/or double-stranded (ds) RNA of reovirus serotype 3 (ST3 virus) is lipofected into L929 mouse fibroblasts together with a rabbit reticulocyte lysate in which ss or melted dsRNA has been translated. After 8 hr the cells are then infected with a helper virus, ST2 reovirus. Virus yields are harvested 24 or 48 hr later. Under these conditions virus that forms plaques by 5 days is produced, all of which is ST3 virus; ST2 virus forms plaques only after 12 days. No reassortants are present among the progeny. The virus yields are about 0.2 PFU/cell; immunofluorescence assays show that this progeny is derived from about 4% of the cells. Double-stranded RNA is 20 times as infectious as ssRNA; ds and ssRNA together yield 10 times as much infectious virus as dsRNA alone, the reason being that dsRNA greatly increases the infectiousness of ssRNA. All species of both ss and dsRNA are required for the operation of this additive effect. The primed rabbit reticulocyte lysate is not essential, but increases virus yields by 100-fold. Its activity is proportional to the time for which translation has proceeded; however, this activity is not due solely to newly synthesized proteins because destruction of the RNA following translation abolishes activity which cannot be restored by simple addition of more RNA. Translation of all species of RNA is essential. Whereas no reassortants are formed when ss and dsRNA of different genotypes are lipofected together, mixtures of dsRNAs of different genotypes do yield reassortants. The same is true for such mixtures of ssRNA. These findings will permit the introduction of new or altered genome segments into the reovirus genome. They open the way to the identification of encapsidation and assortment signals on reovirus genome segments, the characterization of functional domains on reovirus proteins, and the development of reovirus as an expression vector. PMID- 2238474 TI - Molecular characterization of the Borna disease agent. AB - Borna disease (BD) is a neurologic syndrome characterized by profound disturbances in behavior and the accumulation of specific antigens in limbic system neurons. The potency of brain homogenates from animals with BD to cause disease in normal animals is reduced by exposure to detergents. We have recently described isolation and characterization of clones derived from the BD agent. Here we present evidence that suggests that the BD agent is a negative-sense, single-strand RNA virus. The 8.5-kb genome of this virus appears to be associated with nuclei and encodes two major RNA transcripts of 2.1 and 0.8 kb. PMID- 2238475 TI - Identification and sequence analysis of the maize stripe virus major noncapsid protein gene. AB - The maize stripe virus (MStV) major noncapsid protein (NCP) gene was characterized, and the location of the NCP gene was identified among the 5-RNA, 18-kb genome. A 12-amino-acid sequence of the NCP was compared with nucleotide sequence data for MStV RNAs 3 and 4 and was found to align perfectly within a 528 nucleotide open reading frame (ORF) of RNA 4. The amino acid composition of purified NCP was almost identical to that deduced from the putative coding region. The deduced NCP molecular weight was 19,815, very similar to that determined by SDS-PAGE analysis of the purified NCP. In vitro transcription and translation analysis of the cDNA representing this region showed unequivocally that this region encoded the NCP. Primer extension analysis using a synthetic oligonucleotide complementary to a sequence near the 5' end of the coding region revealed that the NCP ORF is located 61 nucleotides from the 5' end of RNA 4. PMID- 2238477 TI - Expression of gag precursor protein and secretion of virus-like gag particles of HIV-2 from recombinant baculovirus-infected insect cells. AB - A recombinant baculovirus carrying the gag gene but lacking the protease coding sequences of human immunodeficiency virus type 2 (HIV-2) has been constructed. When this recombinant baculovirus is used to infect insect cells, a high level of gag precursor protein, gag pr41, is expressed. Electron microscopy showed that the majority of gag pr41 was budding through the plasma membrane and being released into the culture medium in spherical virus-like particles with a diameter of approximately 100 nm. Metabolic labeling demonstrates that gag pr41 is myristylated. Our results demonstrated that HIV-2 gag pr41 can be assembled into virus-like particles in the absence of other HIV proteins. Rabbits immunized with purified gag pr41 particles produced high-titer antibody and Western blot analysis showed that anti-gag pr41 rabbit sera recognize p17, p24, and p55 gag proteins of HIV-1. These results show that gag pr41 particles are highly immunogenic and that gag proteins of HIV-1 and HIV-2 have similar antigenic epitopes. PMID- 2238476 TI - Hepatitis B virus propagated in a rat hepatoma cell line is infectious in a primate model. AB - The human hepatitis B virus (HBV) produced by a rat hepatoma cell line through transfection with HBV DNA is infectious in the human primate model--chimpanzee. Since hepadnaviruses are known to have an extremely narrow host range, our results support the idea that the host species barrier of HBV infection resides on the penetration/adsorption step rather than any postpenetration intracellular event during the virus life cycle. PMID- 2238478 TI - Alternative splicing of hepatitis B virus RNAs in HepG2 cells transfected with the viral DNA. AB - We identified a novel spliced RNA of 2.6 kb from a human hepatoma cell line HepG2 transfected with the hepatitis B virus (HBV) genome. The splicing acceptor site of the novel 2.6-kb RNA (position 489) was shown to be common to that of the previously described 2.1-kb spliced RNA which codes for an altered core antigen lacking the carboxy-terminal amino acid, cysteine. However, the donor site of the 2.6-kb RNA is different from any of the spliced RNA reported and located at 538 nucleotides (nt) downstream of the donor site of the 2.1-kb RNA. Introduction of single-base change mutations in the consensus sequence of the donor site of the 2.1-kb RNA maintained the splicing by using the cryptic donor site. The amount of the 2.6-kb spliced RNA was unchanged by these mutations. These results suggest independent regulations for the synthesis of the 2.1- and 2.6-kb spliced RNAs. PMID- 2238479 TI - Two bases are deleted from the termini of HIV-1 linear DNA during integrative recombination. AB - Proviral integration is a required step in the retrovirus life cycle. The mechanism of integration involves specific modification of the ends of linear viral DNA and subsequent recombination with host sequences. Integration results in the limited loss of sequence information at the termini of the viral genome. The composition of the intact linear DNA termini were inferred by sequencing the 2-long terminal repeat (2-LTR) circle junction that is formed when the linear molecule undergoes intramolecular, blunt-end ligation. The junction sequence contained the nucleotides GTAC that were not present at the ends of the integrated provirus. Comparison with the sequence of the LAV-1 strain of HIV-1 demonstrated that the GT dinucleotide derived from the right-hand terminus (U5) of the linear viral DNA and the AC dinucleotide came from the left-hand terminus (U3). Therefore, the corrected size of the LAV-1 LTR is 637 bp. This conclusion was confirmed independently by assessing the structure of linear viral DNA in acutely infected T cells. A portion of the population of linear HIV-1 DNA molecules were specifically deleted at their 3' ends; the extent of this deletion was 2 bases. This result is consistent with the activity of viral integrase protein on linear viral DNA and it accounts for the structure of integrated HIV-1 proviruses. PMID- 2238480 TI - Inhibition of uncoating of tobacco mosaic virus particles in protoplasts from transgenic tobacco plants that express the viral coat protein gene. AB - The uncoating of tobacco mosaic virus (TMV) particles in protoplasts isolated from leaves of transgenic tobacco plants that express the TMV coat protein gene was investigated. Extracts of these protoplasts collected up to 1 hr after inoculation with TMV contained fewer of the complexes ("striposomes") thought to be involved in cotranslational disassembly of virus particles than did extracts of protoplasts that do not express the viral coat protein gene. These results are consistent with the hypothesis that TMV coat protein-mediated resistance is at least in part the result of inhibition of the uncoating of the virus particles in the inoculum. PMID- 2238481 TI - The putative RNA replicase of potato virus M: obvious sequence similarity with potex- and tymoviruses. AB - On the basis of comparison of the protein sequences of the putative virus specific replicases, carlaviruses can be placed in the "Sindbis-like" supergroup of plus-stranded RNA viruses. Among these, the amino acid sequences of the replication proteins of potex- and tymoviruses showed the highest similarity to potato virus M. The possible functions of conserved domains are suggested to be methyltransferase, nucleotide-binding domain, and RNA polymerase. PMID- 2238482 TI - Complementation of coat protein-defective TMV mutants in transgenic tobacco plants expressing TMV coat protein. AB - Transgenic tobacco plants (Nicotiana tabacum cv. Xanthi) which express tobacco mosaic virus (TMV) U1 strain coat protein (CP) can complement both the assembly and the long-distance spread of CP-defective (DT1) or coat proteinless (DT1G) mutants of TMV. Both mutants arose spontaneously from PM2 and exist only as unencapsidated RNA in the inoculated leaves of control tobacco plants, where they are unable to form virus particles or to spread systemically. TMV CP expressed in transgenic tobacco plants [CP+ line 3404; P. Powell Abel, R. S. Nelson, B. De, N. Hoffman, S. G. Rogers, R. T. Fraley, and R. N. Beachy, 1986, Science 232, 738 743] was able to package some of either mutant viral RNA into TMV-like particles in vivo and resulted in the long-range spread of infection. In vivo encapsidated DT1 RNA was recovered and reinoculated onto control or new CP+ transgenic tobacco plants. Localized infection of control plants confirmed that no RNA recombination or reversion of the mutant RNA to wild-type had occurred during passage in the first CP+ plant. In contrast, encapsidated DT1 RNA was unable to produce even local infection in CP+ transgenic plants confirming that CP-mediated protection operates during the early stages of virus infection, including particle uncoating. By positive complementation, these results also confirm that TMV CP is required for the long-distance spread of infection. PMID- 2238483 TI - Crystallization of cauliflower mosaic virus. AB - Cauliflower mosaic virus has been crystallized in hanging and sitting drops. The hexagonal and octahedrally shaped crystals are up to 0.5 mm in mean diameter. The octahedrally shaped crystals diffract to about 27 A resolution. The results are discussed in relation to the lability and aggregation of the virions. PMID- 2238485 TI - [Medical care for burn patients on board naval fighting ships]. PMID- 2238484 TI - Plan and operation of the NHANES I Epidemiologic Followup Study, 1986. AB - This report describes the plan and operation for the 1986 data collection wave of the Epidemiologic Followup to the First National Health and Nutrition Examination Survey (NHANES I). Tracing and data collection were conducted on 3,980 persons 55 74 years of age at NHANES I who were not known to be deceased in the 1982-84 data collection wave of the NHANES I Epidemiologic Followup Study. PMID- 2238486 TI - [Delivering medical care to the victims in mass peacetime catastrophes]. PMID- 2238487 TI - [The principles of formulating a pathogenetic therapy in the early period of the crush syndrome]. PMID- 2238488 TI - [The clinico-immunological changes in general cooling of the body]. PMID- 2238489 TI - [The clinical picture and treatment of acute radiation sickness in the recovery period (a review of the literature)]. PMID- 2238490 TI - [Mobile clinico-diagnostic laboratories abroad]. PMID- 2238491 TI - [The current problems of medical support for naval military personnel]. PMID- 2238492 TI - [Ways to improve the primary medical card]. PMID- 2238493 TI - [A "triage post" kit (an innovation suggestion)]. PMID- 2238494 TI - [The current problems in the advanced training of officers of the medical reserve corps]. PMID- 2238495 TI - [The research work and training of the students in a department of management medical staff]. PMID- 2238496 TI - [Criteria for the comprehensive evaluation of the activities of military medical hospital commissions]. PMID- 2238497 TI - [The current problems of specialized proctological care in military medical institutions]. PMID- 2238498 TI - [High-frequency artificial ventilation of the lungs in the prevention of postoperative pneumonias]. PMID- 2238500 TI - [The use of agents to stimulate and correct the immune system in the prevention of infectious diseases among the troops]. PMID- 2238499 TI - [The current trends in the diagnosis and treatment of ankylosing spondylitis]. PMID- 2238501 TI - [Experience in organizing epidemic-control measures in children's summer health promoting institutions]. PMID- 2238502 TI - [An evaluation of the efficacy of health and hygiene measures performed in the barracks]. PMID- 2238503 TI - [The pharmacological correction with asparkam of the functional status of pilots in army aviation in a hot climate]. PMID- 2238504 TI - [The risk factors and prognosis of syncopal states in pilots]. PMID- 2238505 TI - [The biorhythms and work capacity of sailors under hypokinetic conditions]. PMID- 2238506 TI - [The Academic Medical Council of the Central Military Medical Administration (on the 50th anniversary of its formation)]. PMID- 2238507 TI - [The principles of N. I. Pirogov's "system of dispersion" and their development during World War II]. PMID- 2238509 TI - [The effect of a 3-day fast on psychophysical functions in young people]. AB - Presented are results of the effect of a complete three-day fasting with permitted optional water intake on some anthropometric, biochemical-metabolic and functional parameters significant in the assessment of psychophysical fitness of healthy, well-developed and normally-nourished young men aged 19.5 years in average. It was found that a three-day complete fasting with average daily energy expenditure of 14.89 MJ resulted in significant body mass reduction, significant glycemia and respiratory quotient decrease, significant blood urea, keto-bodies and triglyceride levels increase and in significantly reduced endurance at strenuous physical work performance. PMID- 2238508 TI - [Lyme disease in Yugoslavia]. AB - Presented are results of the last five-year period study of the lyme disease in Yugoslavia. On the basis of published papers and professional communications over 2500 cases of lyme disease.were detected in our country within this period. Presented are common epidemiologic and clinical features of the disease and particularly cases diagnosed in Belgrade. Since 1987 a group of various specialists has been working on the research project in collaboration with many centres in the country. Indirect immunofluorescence test as the diagnostic laboratory technique has been introduced in the Military Medical Academy in Belgrade in 1987. First species of Borrelia burgdorferi from ticks Ixodes ricinus have been isolated and cultivated in May and June 1990. Current problems concerning research work, medical and epidemiological aspects of the lyme disease are presented. PMID- 2238510 TI - [Working environment conditions and occupational disorders in artillery unit personnel]. AB - Occupational environment risk factors and health status of 172 soldiers and 89 officers were examined aiming to discover early signs of occupational diseases and disorders in artillery personnel. Among all physical and chemical risk factors noise caused by artillery and infantry firing (140 to over 170 dB) were the most frequent and among occupational diseases/disorders only perceptive hearing disorders being very frequent in artillery officers (65.22%) were found out. Preventive measures against occupational environment risk factors were suggested. PMID- 2238511 TI - [Preparation of a DNA probe for thermolabile toxin and its use in the identification of enterotoxic Escherichia coli]. AB - Enterotoxic Escherichia coli (ETEC) having a gene for thermolabile toxin were identified by the hybridization technique. HindIII-SmaI fragment with 423 basic pairs (dp) including subunit portions A and B of the gene for thermolabile toxin (elt) was used as the DNA probe. PMID- 2238512 TI - [Use of the ELISA immunoenzyme test and indirect immunofluorescence in the diagnosis of a toxoplasmosis epidemic]. AB - Etiologic agent of lymphadenitis outbreak in one our military environment was detected by two serologic tests: ELISA (enzyme-linked immunosorbent assay) and indirect immunofluorescence test (IIF) both specific for IgM and IgG antibody detection in toxoplasmosis diagnosis. IgM-ELISA analysis of the first serum sample taken from a group of 79 soldiers with lymphadenitis was positive in 65 examinees (82.28%) and IgG-IIF technique in 52 (65.82%). In a group of 33 soldiers from the same unit with no signs of the disease IgM-ELISA test was positive in 12 (36.36%) and IgM-IIF in 9 (27.27%). In a group of 40 officers from the unit with the disease outbreak specific IgM antibodies were found by both tests only in the head cook. IgM antibodies were not found in a control group of 102 healthy soldiers from other units of the same garrison. Results of this investigation thermal injury showed variations in immune response to infection in dependence on trauma effect duration (in dependence on the phase). In the early posttraumatic phase organism is capable to react effectively to the inoculated infective agent and in the late posttraumatic phase this reaction is much less effective. Authors conclude that these results may influence upon the thermal injury management strategy in dependence on the trauma effect duration. PMID- 2238513 TI - [Methods for the detection of salmonellae in food]. AB - Presented are results of modern immunological and culture medium techniques for the salmonella isolation from chicken trunks compared with those obtained by standard technique (ST). By using fluorescent antibody technique (FAT), enriched serum techniques (ES) and immune stain-reaction (ISR) a larger number of positive samples was detected (31%-41%) in comparison with standard culture medium techniques (ST) (25%). Statistically significant differences were obtained by FAT. By both Rappaport-Vassiliadis (RV) and modified semi-solid Rappaport Vassiliadis (MSRV) culture medium techniques about thrice higher percentage of salmonella positive findings were obtained than in comparison with the standard techniques. Compared to RV, the MSRV culture media technique reduces the salmonella isolation period for 48. PMID- 2238514 TI - [Acute gastroenteritis of viral etiology]. AB - Retrospective analysis of own experiences and investigations concerning the role of the viral etiology in acute gastroenteritis were presented. Stools of children and soldiers with acute gastroenteritis were examined by electron microscopy. The most frequent causative agents were rotaviruses and much less frequently found were other viral particles of: coronaviruses, adenoviruses, Norwalk-like viruses, astroviruses, caliciviruses and "small round viruses". PMID- 2238515 TI - [Surveillance methods in hospital infections]. AB - In the prevalence study of postoperative pyogenic-inflammatory disease in 1,000 operated patients three parallel controls have been undertaken: comprehensive prospective control, current state and standard control. Current prevalence control has been proved the most suitable, practical and for hospital personnel the most acceptable control method. PMID- 2238516 TI - [Seasonal distribution of intestinal fungal infection by the genus Candida]. AB - To follow-up seasonal distribution of intestinal fungal infection by Candida genus (CGF) in patients and healthy subjects 3786 stool samples have been examined. There were 1302(34.4%) stools of patients and 2484 of healthy subjects of which 421 (16.9%) samples were infected by CGF. In both groups of examinees infection by CGF had a seasonal character. Significantly lower incidence was found within the period January-March (the three-month average percentage of infection was 25.2%, that is, 13.9%) than within the period October-December (the three-month average percentage of infection distribution was 42.7%, that is 20.4%). PMID- 2238517 TI - [Health and medical problems in supplying water to the armed forces during times of peace]. PMID- 2238518 TI - ["Health for All by the Year 2000" with special emphasis on the prevention of chronic non-infectious diseases]. PMID- 2238519 TI - [Health problems of enclosed environments at work and in the home]. PMID- 2238520 TI - [Various indices of lipid metabolism in patients with gastroduodenal pathology]. AB - Lipid metabolism was studied in patients with impairments of gastroduodenal tract before and after treatment. The data obtained suggest that the treatment of these patients should involve both antioxidants and angioprotective drugs in order to prevent vascular deteriorations. PMID- 2238522 TI - [The effect of tuftsin on various aspects of metabolism in the sensorimotor system of the animal brain]. AB - Rates of synthesis and degradation of monoamines, acetyl choline and protein were distinctly altered in cortex-subcortex structures of the brain locomotory system after a single administration of tetrapeptide tuftsin Thr-Lys-Pro-Arg during the period 15-30 min of its pronounced effect on the animal motor activity. Correlation between the functional and morphological alterations in cellular and subcellular brain structures, caused by the peptide administration, is discussed. PMID- 2238521 TI - [Molecular mechanism of hemosorption]. AB - Several humoral and intracellular components of blood were investigated in patients with esophageal carcinoma treated with preventive hemosorption + chemotherapy, and also in patients with purulent complications after surgery before hemosorption, during hemosorption and 3 hrs, 1, 3 and 7 days after hemosorption. It was demonstrated that during hemosorption and in the first days following it no significant changes occurred either in blood count or in protein content, protein composition, levels of alpha 1-AT, IgG, IgA and IgM in blood plasma. Preventive hemosorption did not cause hypo- or dysproteinemias in these patients. Hemosorption led to normalization of certain biochemical indices of blood: increase in BAEE activity and decrease in the level of middle molecular toxins, which indicated the reduction of endotoxicosis in patients. During hemosorption there was a marked (100-200 times) increase in blood plasma of lactoferrin, which is a component of specific granules in neutrophils. It is assumed that the leading modifying mechanism of action of hemosorption is an output of physiologically active components the main of which is lactoferrin. PMID- 2238523 TI - [The effect of 24,25-dihydroxyvitamin D3 (dioxyvit) on Ca metabolism and immune status during chronic kidney failure]. AB - Active metabolite of vitamin D3, 24R,25 (OH)2D3 (dioxyvit) was used at a daily dose of 100 micrograms in treatment of children affected with tubulointerstitial disease of kidney and with chronic glomerulonephritis under conditions of kidney insufficiency. The drug exhibited distinct normalizing effect on patterns of calcium metabolism: increase of total and ionized Ca2+ and of 25-OHD, decrease in concentration of parath hormone and osteocalcine in blood serum as well as on immunological parameters: restoration of decreased content of T- and 0 lymphocytes. Concentration of receptors of hormonal form of 1,25(OH)2D3 was found to be minimal in lymphocytes under conditions of chronic kidney insufficiency, while their expression, after the dioxyvit action, was detected only in patients with glomerulonephritis. Specific calcitropic effect of dioxyvit with simultaneous correction of vitamin D deficiency were apparently responsible for high efficacy of the drug in treatment of calcium metabolism and immunity impairments in children with renal deteriorations at the step of chronic kidney insufficiency. PMID- 2238524 TI - [Ethanol and protein biosynthesis in the animal liver (review of the literature)]. AB - Protein biosynthesis was markedly altered in liver cells after acute and chronic administration of ethanol in vivo and in vitro. The effects were dose- and time dependent. Synthesis of cytoplasmic and nuclear proteins was inhibited in hepatocytes. In chronic intoxication activity of fibroblasts and collagen synthesis were stimulated. The data obtained suggest that inhibition of amino acids activation, impairment of translation and transcription were involved in mechanisms of the ethanol toxic effects on liver tissue. At the same time, negative effects of ethanol and its metabolites appear to be related to post translation modification of polypeptides. PMID- 2238525 TI - [ADP-induced aggregation of human platelets in diabetes mellitus]. AB - Dilution of thrombocyte-rich blood plasma (down to 2.5 x 10(8) thrombocytes/ml) enabled to avoid an irreversible phase of the ADP-induced thrombocyte aggregation; the reversible phase of aggregation was followed by deaggregation. The reversible aggregation of thrombocytes was studied in healthy persons and patients with diabetes mellitus within wide ranges of ADP concentrations (including 10 microM) using the diluted blood plasma. Thrombocytes of the patients with diabetes mellitus of the I and II types were found to be 1.6- and 2.33-fold more sensitive to the ADP aggregating effect as compared with thrombocytes of healthy persons. The elevated rate of thrombocytes aggregation in diabetes mellitus appears to be related to early decrease in activity of thrombocyte guanylate cyclase and to its ability to be activated. PMID- 2238526 TI - [Formation of interpolymer complexes with human seminal plasma proteins]. AB - Formation of interpolymeric complexes was studied involving human lactoferrin, prostate beta-globulin, specific acid phosphatase and polymers of various nature: polysaccharides--heparin, dextran sulfate; polylysine-16; proteins--human albumin, equine hemoglobin, gelatin, protamine. Immunoelectrophoresis proved to be a sensitive procedure to register the interpolymeric complexes formed. Electrophoretic mobility of lactoferrin and prostatic beta-globulin was most distinctly altered. Mechanisms of the complexes formation, including ionic and hydrophobic interactions, are discussed. PMID- 2238527 TI - [Plasma and platelet lipids in patients with newly diagnosed angina and chronic heart disease]. AB - In patients with ischemic heart disease impairments in blood plasma lipid spectrum were more distinct in the chronic form of the disease. At the same time, the phospholipid composition was altered in thrombocytes as compared with that of persons free of ischemic heart disease and of stenosing coronary atherosclerosis. PMID- 2238528 TI - [Incidence among men of atherogenic potential of the serum detected in a culture of mouse peritoneal macrophages]. AB - Blood serum of 63 persons out of 191 men examined, randomly selected among non organized population, caused in primary culture of mice peritoneal macrophages the 1.3-4-fold increased accumulation of intercellular cholesterol. Blood serum of other 128 men studied did not exhibit any atherogenic properties in the culture. The atherogenic potential of blood serum did not correlate with content of blood serum lipids, apolipoproteins B and A-I, while it correlated with the ratio apo B/apo A-I in blood serum and with one of ischemic heart disease risk factors--increased arterial pressure. Blood serum atherogenic potential, detected in experimental model, appears to be involved in development of human atherosclerosis. PMID- 2238530 TI - [Mitochondrial oxidation in the liver during visceral-ischemic shock]. AB - Distinct decrease in respiratory and phosphorylating functions of liver mitochondria was found under conditions of visceral-ischemic shock induced in rabbits after 2 hrs occlusion of superior mesenteric artery and the subsequent step-by-step revascularization. Endogenous intoxication was mainly responsible for inhibition of electron transport through respiratory chain. Impairment of mitochondrial oxidation is one of important factors related to development of the shock "irreversible" phase. PMID- 2238529 TI - [The effect of ascorbate, NADPH and chloditan on lipid peroxidation in the adrenal glands of dogs and guinea pigs in vitro]. AB - Lipid peroxidation was studied in dog and guinea pig adrenal cortex homogenates in vitro in presence of ascorbate, NADPH and I-(o-chlorophenyl)-I-(p chlorophenyl)-2,2-dichloroethane (o,p'-DDD, chloditane) the substance exhibiting the specific impairing effect on human and dog adrenal gland cortex. The higher rate of spontaneous lipid peroxidation was detected in adrenal gland homogenates of guinea pig. NADPH inhibited accumulation of hydroperoxides in dog adrenal gland homogenates, while ascorbate-Fe2(+)-activated lipid peroxidation. Chloditane at concentrations 15.6 and 156 microM decreased the rate of spontaneous lipid peroxidation in dog adrenal gland homogenates and increased--in guinea pig preparations. Chloditane decreased distinctly the rate of lipid peroxidation in guinea pig adrenal gland homogenates, which was stimulated by ascorbate. PMID- 2238531 TI - [The effect of progesterone on metabolism of cholesterol esters in macrophages cultured with acetylated low density lipoproteins]. AB - Effect of progesterone on esterification of free cholesterol, on content of free cholesterol and its esters was studied in rat macrophages, cultivated in presence of acetyl-derivatives of low density lipoproteins (Ac-LDL), as well as on mobilization of cholesterol from macrophages. Progesterone at a dose of 0.5-10 micrograms per I ml of cultivating medium caused dose-dependent inhibition of I 14C-oleate incorporation into cholesterol esters of macrophages cultivated with Ac-LDL (50 micrograms of protein/ml). In the medium free of LDL progesterone caused an increase of cholesterol in macrophages by 45%, while addition of 100 micrograms/ml LDL led to a decrease of free cholesterol by 20% of the initial level. If macrophages pre-enriched with 4-C14-cholesterol were cultivated in LDL containing medium, progesterone increased the 4-14C-cholesterol liberation into medium and decreased the cholesterol content in macrophages. Under conditions of macrophages incubation in the LDL-free medium, progesterone increased the free cholesterol content in these cells but did not affect the 4-14C-cholesterol liberation into medium. The data obtained suggest that the progesterone-induced inhibition of free cholesterol esterification may increase its mobilization from macrophages only if the LDL acceptor function is unaltered. PMID- 2238532 TI - [Lysosomal hydrolases of various rat organs in the process of cell nutrition]. AB - Activity of lysosomal proteinases cathepsins A, B, C, D, H and L was studied in liver, kidney, spleen, thymus, heart, skeletal muscle and brain tissues of rats, maintained on full value diet, on a diet free of proteins and on the diet enriched with methionine. Distinctly dissimilar reactions of thiol-dependent proteinases was detected in liver, heart tissues and skeletal muscles as compared with the reaction of cathepsins A and D; activity of cathepsins B, H and L was decreased 1.5-2-fold in the animal groups maintained on diets both free of proteins and enriched with methionine. The data obtained suggest that concentration of endogenous inhibitors of lysosomal thiol-dependent proteinases rather than content of SH-groups in tissues was responsible for alterations of their activity under conditions of protein starvation. PMID- 2238534 TI - [Heparin-histamine complex, its physico-chemical and biological properties]. AB - Complexes between heparin and histamine at various ratio exhibited various physiological activity. The complex containing heparin-histamine at the ratio of 6:1, 10:1 or 15:1 showed anticoagulation, antipolymerization and nonenzymatic fibrinolytic effects. The complex dissociated in circulation within 90 min after its administration. This complex effected also the rheologic properties of blood. PMID- 2238533 TI - [The effect of ascorbic acid on the collagen synthesis in skin fibroblasts of children with funnel chest]. AB - Relative synthesis of collagen was studied in skin fibroblasts of children with funnel chest and of corresponding age children (control) in presence of ascorbic acid. In presence of ascorbic acid the rate of collagen synthesis was 2-2.4-fold lower that in corresponding controls both in proliferating and stationary cultures. At the same time, relative synthesis of collagen was quite similar both in the patient and control fibroblasts in presence of ascorbic acid. Estimation of the 14C-Hypro/14C-Pro ratio in collagens isolated from cultural media showed that there was no difference in the hydroxylation rate of collagens in control and patient fibroblasts. These data suggest that funnel chest is one of the forms of systemic connective tissue diseases, which impaired mainly the cartilages. PMID- 2238535 TI - [Vitamin B6 level in the cerebrospinal fluid and plasma of children with acute leukemia]. AB - Content of pyridoxal in cerebrospinal fluid exceeded its level in blood plasma of healthy children. Transport of pyridoxal through hematoencephalic barrier was decreased in children with acute leukosis, especially, with neuroleukosis, while content of pyridoxal-5-phosphate was similar to normal values. Possible mechanisms are considered which are involved in stabilization of pyroxal-5 phosphate content in cerebrospinal fluid of patients with acute leukosis, when transport of pyridoxal was impaired in central nervous system. PMID- 2238536 TI - [Various characteristics of protein-synthesizing apparatus of the myocardium during total ischemia]. AB - A decrease in the rate of protein synthesis as well as an increase in the synthesis time of "medium-size" polypeptide chain were detected in total rabbit myocardium ischemia, which were evaluated using rabbit myocardium cell-free protein-synthesizing systems. The decrease in the synthesis rate of total myocardial proteins was shown to depend on the state of ribosomes function. Redistribution in the pools of membrane-bound and free ribosomes as well as a decrease of polyribosomes amount in total pool of myocardial ribosomes were observed under conditions of total myocardial ischemia. PMID- 2238537 TI - [The study of the additive antioxidative activity of total natural lipid antioxidants]. AB - Kinetics of methyl oleate and ethylbenzene oxidation was studied in presence of tocopherol homologues alpha, beta, gamma, delta, tocopherol derivatives C6 and C11, ubichinol QH2-9, which were isolated from natural lipids. Effects of various natural antioxidants in mixtures were interindependent. PMID- 2238538 TI - [Inhibition of the angiotensin-converting enzyme from bovine kidney by organophosphorus analogs of amino acids]. AB - Reactions of amino acid phosphoorganic derivatives with angiotensin-converting enzyme (dipeptidyl carboxypeptidase) were studied. Substitution of the amino acid carboxyl group by HS- or P(O) (OH)2-groups did not cause the enzyme considerable inhibition. The enzymatic activity was inhibited by 20-50% in presence of 1 X 10( 3) M Asp, Met and Cys phosphoorganic derivatives. These amino acid derivatives may be used as potential antihypertensive drugs because of their metabolic stability and inhibitory action on the enzyme. PMID- 2238539 TI - [Immunochemical characteristics of vibrio neuraminidases isolated from aerated culture filtrates]. AB - Immunochemical analysis of neuraminidases, isolated from choleraic and non choleraic vibrios, was carried out. Antineuraminidase antiserum was used in procedures of immunoelectrophoresis, diffusion precipitation in agar gel and disc immunoelectrophoresis in polyacrylamide gel. Antigen composition of neuraminidases was shown to be similar both in choleraic and non-choleraic vibrios. PMID- 2238540 TI - [The use of biochemical blood indices for the laboratory diagnosis of internal diseases using the automated complex device-computer]. AB - Application of biochemical parameters of blood, reflecting disturbances in lipid, protein, carbohydrate, pigment and water-saline metabolism for diagnostics for internal organs diseases is discussed. Methods of clinical biochemistry in combination with subsequent automatic processing of the data obtained on the basis of probability theory and mathematical statistics methods can be used for preliminary computer diagnosis and further examination of a patient, as well as for construction of specific complexes of symptoms for some diseases. Due to their mobility, the preliminary computer diagnostics data can be successfully applied to different pathologies and groups of population. PMID- 2238541 TI - [Express-method of determination of DNA-binding proteins in the mammalian blood]. AB - Quick test for estimation of DNA-bound proteins (PBD) in mammalian blood serum involved filtration of blood serum through Wathman filters containing DNA. DNA was fixed in the Wathman filters by means of UV irradiation. Some physicochemical and chromatographic properties of PBD from mice blood serum were studied. The data obtained suggest that blood serum PBD constituted one of gamma-globulin fractions. Applicability of the PBD test for studies of tumoral diseases was shown using mice with Ehrlich ascites carcinoma. PMID- 2238542 TI - [A new method of purification of L-lysine-alpha-oxidase from the fungus Trichoderma]. AB - A new procedure is developed for purification of the antitumoral enzyme L-lysyl alpha-oxidase from Trichoderma sp. The procedure included two steps: hydrophobic chromatography on butyl sylochrome C-80 and chromatography using biospecific sorbent AH-Sepharose. The simplified procedure enabled to increase distinctly the specific enzymatic activity from 30 to 50 IU/mg in the preparation obtained with a good yield. PMID- 2238543 TI - [A modified method of determination of the total serum antioxidant activity]. PMID- 2238544 TI - [The role of beta-glucuronidase in the tumor process and cancer prevention]. PMID- 2238545 TI - [Enzymatic imprinting and its possible significance in carcinogenesis]. PMID- 2238546 TI - [The effect of surgical trauma on the metabolism of essential fatty acids in patients with cancer of the esophagus and stomach]. AB - The dynamics of levels of essential fatty (linolic and arachidonic) acids in blood plasma and erythrocytes as well as that of free fatty acids fraction versus duration of surgery was assessed by gas chromatography in 49 patients with cancer of the esophagus and gastric cardia. Surgical procedures lasting longer than 5 hours are followed by overmobilization of essential fatty acids from body lipids their endogenous store being depleted. As a result, a double increase in the level of free arachidonic acid, an immediate prostaglandin precursor, develops to satisfy the body's augmented requirements in essential fatty acids due to application of aggressive surgical procedures. PMID- 2238547 TI - [Malignant histiocytosis in children]. AB - The analysis of peculiarities of clinical course and morphology of malignant (acute) histiocytosis in 50 pediatric patients made a case for identification of the disease as separate pathology of histiocytic sarcoma type. Clinical course features include: lymphadenopathy, involvement of bones and--less frequently- lungs, skin and subcutaneous fat, marked fever and weight loss. Cytologic and histologic examination show polymorphic tumor cells of varying degree of differentiation, with blasts predominating. Well-developed Golgi complex, presence of lysosomes, phagosomes and erythrophagocytosis are among the characteristic ultrastructural features of the disease. PMID- 2238548 TI - [The prognostic significance of the anatomical forms of esophageal cancer]. AB - Among the great variety of anatomic patterns of esophageal cancer growth, three basic patterns--exophytic, mixed and endophytic--should be distinguished. Anatomic pattern of growth is one of the basic prognostic criteria for tumor stage assessment. This finding is supported by five-year survival evidence for cases of radical surgery: 58.8 +/- 10% with exophytic form, 16.6 +/- 10%- ulcerative infiltrative and 3.3 +/- 6% with diffuse infiltrative pattern of tumor growth. PMID- 2238549 TI - [An analysis of the oncologist personnel in some economic and geographical regions of the USSR]. AB - The study of age and sex structure, length of service and proficiency of clinical oncologists showed oncologic dispensaries to be largely staffed with well-trained physicians. However, the following problems still existing in the rural oncologic service were identified: no oncologic offices in a third of rural areas, many vacancies of district oncologists are still unoccupied, oncologic care is often given by specialists other than oncologists and finally, postgraduate training standards do not meet the requirements of present-day oncology. PMID- 2238550 TI - [The clinical x-ray diagnosis of pulmonary hamartomas]. AB - A clinico-roentgenologic study of 67 patients with hamartoma of the lung was carried out. Hamartoma could not be even suggested unless X-ray examination was performed but even this procedure sometimes failed to identify the disease. It was far from being each case that typical roentgenologic features of hamartoma were observed. Transthoracic needle biopsy may be helpful in identifying the nature of a roentgenologically detected tumor. Roentgenologically, hamartoma should be first of all distinguished from peripheral lung cancer. When clinico roentgenologic and needle biopsy data are inconclusive with respect to lung cancer diagnostic thoracotomy should be performed. PMID- 2238551 TI - [A program to instruct women in breast self-examination]. AB - The study was concerned with analysis of the second stage of evaluation of a breast self-examination training program aimed at early detection of cancer. A total of 60,079 of women were recruited into the WHO/USSR Project in Moscow in 1985-1988: study group--30,465 and controls--29,614. At 6 months, 52.5% of women performed breast self-examination on a regular basis whereas at 12 months the percentage decreased to 42.0. Breast cancer was diagnosed in 6 out of 11,548 females of the study group (stage I--1 case, stage II--3 and stage III--2 cases) and in 10 out of 23,083 controls (stage I--2, stage II--5, stage III--2 and stage IV--1 patient). In the study group, medical advice was sought 4.5 times more frequently than in controls. PMID- 2238552 TI - [Ultrasonically guided aspiration biopsy in the diagnosis of liver tumors]. AB - The paper is concerned with the analysis of the results of sonographically guided biopsy of hepatic tumors which had been carried out in 30 outpatients suffering primary cancer of the liver (3 cases), metastases (16), lymphosarcoma (2), cysts (2), adenoma (2), hemangioma (4) and hydatidiform mole (1 patient). The sensitivity of the method in tumor diagnosis was 89%, specificity--80%. Ultrasonographic features of the liver pathologies were studied versus morphologic type. Indications and technical requirements for ambulatory ultrasonographically guided biopsy of the liver are discussed. PMID- 2238553 TI - [Drainage-free ureterocutaneostomy]. AB - Drainage-free cutaneous fistula of the ureter is suggested to assure permanent extravesical outlet of the urine in patients with incurable tumor-induced obstruction of the pelvic segment of the ureter. Fistulous orifice is formed with the aid of a triangular flap sitting on a pedicle; the flap is placed into a longitudinal incision in the stump of the drained ureter. Fifteen ureteral fistulas were formed in nine patients. Fourteen of them functioned reliably for several years without causing renal complications. PMID- 2238554 TI - [The readaptation problems of cancer patients]. AB - The paper discusses certain problems involved in communication between physician, cancer patient and society. The authors suggest that information given to a cancer patient on his or her diagnosis should be determined by the patient's willingness to know and prognosis. Also, suggestions on improvement of treatment of cancer patients of clinical group 4 are made. PMID- 2238555 TI - [The correlation of the lymphographic and pathohistological changes in the postmastectomy syndrome]. PMID- 2238557 TI - [A case of a chondrosarcomatous lesion of the cardiovascular system]. PMID- 2238556 TI - [The prevention of radiation injuries to the rectum and bladder in cervical cancer patients]. PMID- 2238558 TI - [Synchronous early cancer of the esophagus and larynx in a patient with complete situs viscerum inversus]. PMID- 2238559 TI - [Treatment results in ovarian sarcomas]. PMID- 2238560 TI - Semi-quantitative determination of H type 1 and type 2 antigens on buccal epithelial cells and in saliva of secretors and non-secretors. AB - The amount of H antigens on buccal epithelial cells (BEC) of secretors and non secretors was measured by flow cytometry. H type 1 and H type 2 on BEC were detected with fluorescein-labelled Ulex europaeus lectin, and H type 2 was measured with mouse monoclonal antibody. Between 3.5 and 6 times more H antigen was detected on cells from secretors compared with cells from non-secretors. The level of H type 2 was the same on BEC of secretors and non-secretors. Adsorption of H type 1 antigen from secretor saliva onto non-secretors BEC was demonstrated. A simple and sensitive ELISA method was developed for the determination of H in saliva with biotin-labelled Ulex lectin. This system provides a simple means for measuring the amount of H present in saliva and for the determination of secretor status. PMID- 2238561 TI - Acid treatment of platelets as a simple procedure for distinguishing platelet specific antibodies from anti-HLA antibodies: comparison with chloroquine treatment. AB - The identification of antibodies to platelet-specific antigens is important for correctly diagnosing neonatal alloimmune thrombocytopenia, posttransfusion purpura and refractoriness due to platelet-specific antibodies. However, the serologic identification of these platelet-specific antibodies is complicated by the presence of anti-HLA antibodies. We examined and compared the diagnostic usefulness of acid-treated and chloroquine-treated platelets for the discrimination of platelet-specific antibodies from anti-HLA antibodies. The viability of acid-treated platelets is 83.4%, which is better than that of chloroquine-treated platelets (52.6%). The antigenicity of HLA class I antigens of acid-treated platelets was significantly reduced compared with that of PBS- or chloroquine-treated platelets. On the other hand, platelet surface glycoprotein Ib and glycoprotein IIb/IIIa, and platelet-specific antigens were stable following acid or chloroquine treatment. Chloroquine-treated platelets were not suitable targets for analysis by immunofluorescence flow cytometry because of nonspecific fluorescence derived from platelet damage. We conclude that acid treated platelets are more suitable targets than chloroquine-treated platelets for screening for platelet-specific antibodies and also for analyses of the specificity of platelet-specific antibodies. PMID- 2238562 TI - Transmission of HTLV-II via blood transfusion. AB - Transmission of HTLV-I by transfusion is well documented in Japan, where HTLV-I is endemic. In non endemic regions such as the United States, HTLV-I/II infection has been transmitted by transfusion as well, but no effort to distinguish HTLV-I from HTLV-II infection was made in these studies. There is a growing body of evidence that a substantial proportion of HTLV-I/II seropositivity in the US is due to infection with HTLV-II. We report 2 cases of apparent transfusion transmitted HTLV-II infection and discuss the importance of distinguishing between the two viruses in blood donors and recipients. PMID- 2238563 TI - Post-transfusion thrombocytopenia: its duration in splenic and asplenic individuals. AB - Previous work in our department showed that after blood transfusion, the platelet count often falls to levels which are clinically significant. The probable site of platelet sequestration was identified as the spleen, and post-transfusion thrombocytopenia was prevented by blood filters which remove microaggregate debris from the donor blood. Since the duration of the thrombocytopenia has not been investigated, the purpose of the present study was to establish the rate of onset and duration of post-transfusion thrombocytopenia following packed red blood cell transfusions. In addition, the effect of spleen size, patients' diagnosis and post-transfusion history were examined. These observations provide interesting new data on the mechanisms involved in this phenomenon. PMID- 2238564 TI - 'Complete' warm hemolysins producing an autoimmune hemolytic anemia. PMID- 2238565 TI - Immunoblotting of Dr(a-) cells with antibodies to Cromer-related antigens. PMID- 2238566 TI - The impact of preoperative autologous blood donation on orthopaedic surgical practice. AB - We have conducted a retrospective 3-year analysis of our autologous blood donation program to assess its impact on orthopaedic surgery. We conclude: (1) utilization has increased from less than 5% of eligible patients in the first audit interval to nearly 50% in the last audit interval; (2) in the last audit interval, autologous blood donation resulted in a reduction of homologous blood transfusion from 41% in nonautologous blood patients to 14% in autologous blood donors; (3) increasingly conservative transfusion practice is seen for all patients undergoing elective orthopaedic surgery; (4) regional blood centers are responding to increasing requests for autologous blood with programs that are effective in attracting autologous blood donors; (5) on the basis of utilization and efficacy, preoperative autologous blood donation as an alternative to homologous blood transfusion now represents a standard of practice for elective orthopaedic surgery. PMID- 2238567 TI - Moderate and severe reactions during autologous blood donations are no more frequent than during homologous blood donations. AB - Because autologous donation is permitted for donors who do not meet homologous blood donation standards, referring physicians and blood center personnel may be concerned about autologous donor reactions. Small studies have determined that mild reactions do not occur more frequently, but the incidence of rarer, more serious, moderate and severe reactions is unknown. We therefore studied the frequency of reactions during 10,200 autologous and 219,307 concurrent homologous donations at four blood centers. No significant difference was seen for severe reactions: autologous 0.039% (4/10,200), homologous 0.037% (82/219,307) (p = 0.79); moderate reactions: autologous 0.19% (19/10,200), homologous 0.22% (473/219,307) (p = 0.60) or mild reactions: autologous 2.26% (231/10,200), homologous 2.26% (4946/219,307) (p = 0.98). We conclude moderate and severe donation reactions do not occur more frequently among autologous donors who are preselected by referring physicians and screened by blood center personnel. PMID- 2238568 TI - Erythrocyte endogenous proteinase activity during blood bank storage. AB - We studied proteolytic alterations of membrane proteins in ghosts derived from human red blood cells, preserved up to 35 days in the liquid state either as whole blood or with additive solution. The study was carried out by performing sodium dodecyl sulfate polyacrylamide gel electrophoresis of stromal proteins from erythrocytes, either previously treated with proteinase inhibitors or previously incubated in conditions promoting proteolysis. To differentiate the effect of erythrocyte from granulocyte proteinases, the investigation was also carried out in leukocyte-free red cell preparations. The results show: (1) the effects of endogenous proteinases on membrane proteins derived from red cells stored under blood bank conditions; (2) a decrease of proteolytic effects in ghosts derived from red cells which have been submitted to a longer storage; (3) a relevant influence of the red cell resuspending medium before lysis on the time dependent onset and exhaustion of proteolysis in ghosts. The presence of increased proteolysis in ghosts could be regarded as a marker of molecular lesions induced in red cells by storage under blood bank conditions. PMID- 2238569 TI - Comparison of IgM and IgG anti-A and anti-B levels in Asian, Caucasian and Negro donors in the North West Thames Region. AB - This study was undertaken to test the widely held belief that higher levels of immune anti-A and anti-B are characteristic of Negro and Asian populations with a corresponding increased risk factor for AB0 haemolytic disease of the newborn. Overall, 300 serum samples from male and female Asian. Caucasian and Negro blood donors in the North West Thames Region of groups A, B and 0 were collected. The sera were titrated in microplates against pooled group A1 and pooled group B red blood cells. Although the results show that the highest levels for IgG anti-A and anti-B were found in group 0 female Negro donors, statistically these levels are not significantly higher than those of the other group 0 donors tested. We suggest that the potent anti-A and anti-B reported by others in Negro and Asian populations may arise from environmental rather than genetic factors. PMID- 2238570 TI - Serological characterization of murine monoclonal antibodies directed against acquired B red cells. AB - Balb/c mice were immunized with acquired B red cells. Twelve clones specific for acquired B red cells were obtained from two fusions. A detailed investigation of three clones is reported here. These antibodies appear to be directed to the B like epitope since they are inhibited by galactosamine and fail to react after acetylation of red cells. E 231 is an example of a series of antibodies closely specific for acquired B red cells which can be useful in elucidating some AB0 typing problems. E 167 and F 47 showed a cross-reactivity with A1 red cells and a synthetic A trisaccharide. No affinity for B antigen could be demonstrated for any of the antibodies. PMID- 2238571 TI - Erythrocyte antibody screening in solid-phase: a comparison of two solid-phase microplate assays with the indirect antiglobulin test in polyethylene glycol for the detection of irregular erythrocyte antibodies. AB - The screening of a serum for irregular erythrocyte antibodies in the indirect antiglobulin test is a well-established technique. We compared the test results of two different solid-phase microplate indirect antiglobulin tests with a liquid phase indirect antiglobulin test in tubes. Antibody screening with both solid phase microplate techniques proved to be more sensitive than the liquid-phase indirect antiglobulin test. In addition, a difference in sensitivity between the two solid-phase techniques was observed: prior immobilization of test erythrocytes on the microplate followed by incubation with a serum and detection of sensitization with antihuman IgG-coated detector cells gave better test results than secondary immobilization on the microplate of test erythrocytes sensitized with antibodies and an antihuman globulin serum. PMID- 2238572 TI - Long-term intravenous immunoglobulin treatment in patients with AIDS-related complex. PMID- 2238573 TI - Major histocompatibility complex class I to III allotypes in patients with AIDS related complex/Walter-Reed 5, disseminated Kaposi's sarcoma and in normal controls. The ARC-IVIG Study Group. AB - In HIV-infected patients major histocompatibility complex (MHC) class I and II (= HLA-A, B, C, DR) association has been controversial. Of the MHC class III coded complement components C2, BF, C4A/C4B especially C4 allotypes appear of major immunogenetic relevance for their potential differences in virus neutralizing potency and immune complex formation. In the present study 29 patients with AIDS related complex and Walter-Reed 5 ARC/WR5), 35 patients with disseminated Kaposi's sarcoma (KS), and 160 HIV-negative control individuals were compared for MHC class I to III allotypes. Diagnosis of ARC and KS (WR criteria) was done by clinical and laboratory parameters, MHC testing, by standard procedures. An increase in frequency (p less than or equal to 0.05) was observed between ARC/WR5 patients and controls for HLA-B35/CW4, DRW14, a decrease for B16, CW6/DR7. However, values were not significant if corrected for the number of tested antigens. No significant differences were seen between KS and ARC patients or controls for class III allotypes, nor for previously reported associations, e.g. for B8, DR2, DR3, and especially DR5, including the DR5 splits DRW11, 12. The results indicate the lack of a strong MHC association with the investigated antigens in West German Caucasoids, and support the hypothesis of ethnic dependence of HIV-related diseases. The HLA-B35/CW4 increase, also associated with the duplicated C4 A*3 A*2 and the silent C4B*Q0, was more pronounced in ARC patients with progression to AIDS-OI. The increased frequency of C4B*Q0 alleles in these patients was thought to be secondary to a hypothetical increase in 'converted' and dysregulated C4 genes not seen to be associated in this study. PMID- 2238574 TI - Cellular immunologic parameters in HIV-positive patients with AIDS-related complex and intravenous immunoglobulin therapy. AB - In a randomized double-blind longitudinal study with 30 HIV-1-positive patients with AIDS-related complex or stage Walter-Reed 5 disease, the effectiveness of intravenous immunoglobulin (IVIG) was tested for correcting eventual immune dysregulation. Although the IVIG-treated patients showed an improvement of their clinical score, no significant changes were observed in lymphocyte phenotypes, activation markers, immunoglobulins and subclasses, lymphocyte turnover or in indicators of acute inflammation. Since severe bacterial infections or autoimmune processes usually leading to IVIG therapy were not prevalent in the patients of the study, such therapy should probably be reserved for later stages of the disease. HIV-1 antigen expression in blood lymphocytes remained uninfluenced by IVIG treatment. PMID- 2238575 TI - Complement levels and circulating immune complexes in a controlled, longitudinal, multicentre study on effects of intravenous immunoglobulin in adults with AIDS related complex/Walter-Reed 5. The ARC-IVIG Study Group. AB - The complement system, as the effector mechanism of the antigen-antibody reaction, and the levels of circulating immune complexes in a 1-year, double blind, randomized, placebo-controlled study served as laboratory parameters to assess the effect of long-term high-dose intravenous immunoglobulin (IVIG) therapy in 30 adult patients (2 x 15) with AIDS-related complex/Walter-Reed 5 (ARC/WR5). We obtained no evidence of an adverse effect in such patients of high dose IVIG administered over a 6-month period: none of the parameters studied showed a significant difference between the two groups of patients. In both groups, using data before the first infusion or using data of the whole study, a correlation between circulating immune complexes and classical complement pathway activation was found. The most striking increase was seen in the two groups of patients for functional serum factor D. The accumulation of serum factor D was not paralleled by an increase in serum creatinine. In patients with disease progressing from ARC to AIDS within the study period, an accumulation of serum factor D was not more or less pronounced than in those who remained in the ARC stage. Accumulation of factor D was not related to the clinical score as assessed in this study. PMID- 2238576 TI - Comments on the statistical evaluation of the ARC-IVIG Study. PMID- 2238577 TI - [The new management mechanism in public health]. PMID- 2238579 TI - [The temporary loss of work capacity in workers in the hot shops of the metallurgical industry due to diseases of the circulatory organs]. AB - It was established that morbidity with temporary loss of working capacity due to diseases of the circulatory organs showed a tendency towards increase among workers of modern hot shops of the blast furnace, steel-smelting furnace, converter and the steel rolling industry. Most frequent in these category of workers was incidence of ischemic heart disease, hypertensive disease and hemorrhoid. The incidence varied among different professions enumerated above and depended also on the age, working conditions. The nosological entities varied as well. PMID- 2238578 TI - [The cardiopulmonary age of workers in hot jobs in glass manufacture]. AB - Data are reported on the effect of heating microclimate on the enhancement of functional aging of the cardiovascular system in workers of the glass industry. It is shown that enhancement of the aging tempo was noted during the first 5 years of work in condition of hot microclimate and following 15 years of work in these conditions. The enhancement of biological aging of the individual is also influenced by the age of the worker beginning to work in conditions of hot climate. PMID- 2238580 TI - [The effect of leukocyte interferon on the kinin system indices of the blood in patients with acute intestinal infections]. AB - The authors studied the efficiency of using rectally interferon in acute intestinal infections, the influence of the agent on the kinin system in these patients. 42 children with bacterial intestinal infections were examined. They were given rectally 1000 IU of interferon. This results in a rapid disappearance of the intoxication symptoms, signs of lesions of the gastrointestinal tract, normalization of the kinin system indices. PMID- 2238581 TI - [The effect of differentiated treatment on the the indices of the hepatic cholate forming function in patients with chronic enterocolitis]. PMID- 2238582 TI - [The epidemiology of escherichiosis in 2 agrarian regions]. AB - A study of the epidemiology of escherichiosis in two agricultural regions of the Ukraine revealed differences in the etiological structure in the limits of regions, points within a twelve-year period. It is concluded that continuous monitoring of serological pictures of pathogenic Escherichia is necessary. PMID- 2238583 TI - [The use of hemosorption in leptospirosis patients with pronounced thrombocytopenia]. AB - The authors describe a rare case from the clinical practice. Treatment including hemosorption was employed in a 38-year-old with a severe form of icterohemorrhagic leptospirosis accompanied by acute reno-hepatic failure and pronounced thrombocytopenia--15 x 10(9)l. The relative significance of thrombocytopenia as one of the main contraindication to hemosorption is suggested. PMID- 2238585 TI - [Experience in managing a system for the rational utilization of the residual work capacity of agricultural workers]. PMID- 2238584 TI - [The one-stage system in organizing medical first aid for patients with acute myocardial infarct]. PMID- 2238586 TI - [The hemodynamics of the lesser circulation in liver diseases]. AB - The authors analyze data obtained in complex clinico-instrumental examination of the state of hemodynamic of the right compartments of the heart in 45 patients with chronic portal hypertension 20 patients with liver cirrhosis using two dimensional echocardiography. The right ventricle and right atrium were located from the apical position of the gauge in the 4-chamber projection of the heart. Compared were values of areas of heart chambers and rate characteristics of movements of their walls and cusps of the pulmonary artery. Simultaneously ultrasonometry [correction of ultrasensometry] of the venous vessels of the abdominal cavity, liver and spleen was carried out. Signs of portal and pulmonary hypertension, loads on the right heart compartments were found in these two diseases that were more pronounced in patients with liver cirrhosis. PMID- 2238587 TI - [The effect of calcium antagonists on the hemodynamic function in patients with heart failure]. AB - The therapeutic effect of calcium antagonists corinfar and phinoptin was studied in 48 patients with ischemic heart disease with chronic circulatory insufficient (CCI). The hemodynamic effects of these calcium antagonists were characterized by an increase of indices of cardiac contraction and essential reduction of the general peripheral resistance with simultaneous reduction of the left ventricle volumes during diastole and systole. It is concluded that corinfar and phinoptin are indicated in patients with CCI. PMID- 2238588 TI - [The effect of korinfar on the systemic hemodynamics and myocardial contractile function in hypertension patients]. PMID- 2238589 TI - [The transport function of the serum albumin in patients with ischemic heart disease and in persons with risk factors for its occurrence]. AB - Persons of the ischemic heart diseases risk group and patients with ischemic heart disease showed a reduction of the transport function of serum albumin that correlated with the sex and age of examined persons, presence of that of another risk factor of ischemic heart disease as well as with its clinical form of manifestation. Established were correlations between the level of hypercholesterolemia and state of the transport function of serum albumin and a positive effect of sex hormones on the transport function of serum albumin. The obtained data suggest a major role of protein metabolism in the pathogenesis of ischemic heart disease. PMID- 2238590 TI - [The immunological indices of patients who have had a myocardial infarct]. AB - The authors carried out immunological examination of 68 patients with ischemic heart disease with a history of one or several myocardial infarctions. The patients showed changes of the immune status, mainly of the humoral type due to allergic reactions caused by immune complexes and also anaphylactic reactions provoked by IgE-antibodies. The above changes occurred against the background of T-cellular immunodeficiency and increased content of B-lymphocytes. Increase of the level of indices of unspecific defence is a manifestation of compensatory reactions directed to elimination of the increased content of circulating immune complexes from the body of the patients. PMID- 2238591 TI - [Drug interaction with cardiac glycosides (a review of the literature)]. PMID- 2238592 TI - [Dilated cardiomyopathy with a benign course]. AB - Perspective observation of 224 patients with dilated cardiomyopathy showed that in 21 cases (9.4%) the course of the disease was benign characterized by insignificant limitation of their physical condition and its stabilization. Dilatation of the left cardiac ventricle and reduction of its contractile function did not reach significant levels that is caused by a relatively larger as compared with other patients capacity to the development of compensatory hypertrophy. PMID- 2238593 TI - [The use of pulse-width modulation sinusoidal currents in the combined treatment of peptic ulcer]. AB - The efficacy of pulse-duration modulation currents was evaluated in 143 patients with duodenal ulcer at the phase of reducing exacerbation. It was established that pulse-duration modulation currents in T5-T3 parameters produced a positive effect both on the clinical course of the disease and on the functional morphological state of the gastrointestinal system. Absence of side-effects, simplicity and availability allow this method for implementation in the clinical practice of different medical institutions. PMID- 2238594 TI - [Structural changes in the gastric mucosa of patients with rheumatic diseases (a review of the literature)]. PMID- 2238595 TI - [The morphological characteristics of the cardiac lymphatic bed in chronic coronary failure]. AB - A study is presented of the morphological changes of the lymphatic circulation in chronic ischemic heart disease (IHD). Examinations were carried out on clinical material: intraoperative cardiac biopsies and on hearts of patients who died of this disease at the age of 36-59 years. Transmission electron microscopy was used. A clinical comparison was realized of changes of intramyocardial and subepicardial regions of the heart lymph circulation and morphological equivalents of disorders of outflow of lymph from the heart in chronic IHD were evaluated. The obtained data indicate the lymph stasis possessing cardiotoxic and sclerogenous properties is an essential pathogenetic factor of myocardial fibrotization in chronic coronary insufficiency. PMID- 2238596 TI - [Transplantation of the heart and of the heart-lung block (a review of the literature)]. PMID- 2238598 TI - [The immunological reactivity indices of patients with chronic nonspecific lung diseases]. AB - At height of the disease patients with chronic bronchitis showed a reduction of immunological indices of reactivity of the body. A direct dependence was established between the severity of the course of the disease and degree of reactivity reduction. Absence of complete normalization of indices of immunological reactivity at discharge from the clinic indicates incomplete control of the inflammatory process and short-term character of the remission. The reaction of lymphocyte blast transformation may be used for detection of both latent and clinically manifest staphylococcal infection. Increased sensitivity to staphylococcal allergen results in a reduction of the phagocytic activity of neutrophils in patients with chronic bronchitis. PMID- 2238597 TI - [A histophotometric study of the liver dehydrogenases in acute arterial occlusion of the lower extremities]. PMID- 2238599 TI - [The efficacy of kalipsol in the intensive therapy of status asthmaticus]. PMID- 2238600 TI - [Pulmonary ventilation and central hemodynamics in pulmonary tuberculosis patients]. AB - Computerized devices were used for evaluation of the state of pulmonary ventilation and central hemodynamics in 32 patients with pulmonary tuberculosis depending on the spread of the specific process. Patients with limited changes in the lungs, showed disorders of bronchial patency and compensatory increase of organic ejection of the right ventricle. In the presence of spread changes in the lungs the above mentioned changes were supplemented by restrictive ventilation disorders with a reduction of the contractile myocardial capacity. These functional changes should be considered in the treatment of patients with pulmonary tuberculosis. PMID- 2238601 TI - [Central hemodynamics in young and middle-aged patients with the initial manifestations of cerebral circulatory failure]. AB - The authors studied the indices of general hemodynamics in 53 patients with initial manifestations of cerebro-circulatory insufficiency of young and middle age. Young patients suffering of cerebral atherosclerosis and vegetative-vascular dystonia showed a hyperkinetic type of hemodynamics while the middle-aged with atherosclerosis showed the hypokinetic type evidencing abnormal function of autoregulatory mechanisms. PMID- 2238602 TI - [The efficacy of the laser therapy of peptic ulcer patients]. AB - Data are reported of treatment efficacy of 67 patients with gastric and duodenal ulcer. In 52 complex treatment included lasers. It is concluded that employment laser radiation produced a significant analgetic effect and stimulated epithelialization of the ulcer defect. PMID- 2238603 TI - [The neuroendocrine and neurotrophic changes in combined brain concussion and locomotor trauma (a review of the literature)]. PMID- 2238605 TI - [Nervous system involvement in herpes zoster (a review of the literature)]. PMID- 2238604 TI - [Psychoautonomic dysfunction of adaptation origin]. AB - Data are reported of a psycho-vegetative examination in 123 sailors in the dynamics of long-term cruises. A correlation was established in the development of psychological and vegetative disadaptation. The initial stages are characterized by hypersthenic processes in the psychic activity and hypersympathicotonus in the vegetative functions. Three months later the adaptogenesis is prevailed by asthenic processes and by parasympathetic trends of vegetative activity. PMID- 2238606 TI - [The reactivity of the autonomic nervous system in patients with the hypothalamic syndrome]. PMID- 2238607 TI - [The central hemodynamic function of obese patients]. AB - The authors substantiate the employment of radiocardiography for the examination of the cardiohemodynamics in patients with obesity of the III and IV grades. On the basis of a study of the main hemodynamic indices in patients with extreme obesity a trial is made to evaluate the pathogenesis of cardiac insufficiency in these patients. PMID- 2238608 TI - [The effect of low doses of ionizing radiation on human health]. AB - Data are reported on the possible mechanism of biological effects of small doses of ionizing radiation on the human body. The lesioning effect of this radiation resulted in some of the persons in the development of disorders of the function of information and vegetative-regulatory systems determined as a disintegration syndrome. This syndrome is manifested in unspecific neuro-vegetative disorders of the function of most important physiological and homeostatic system of the body leading to weakening of the processes of compensation and adaptation. This condition is characterized by an unspecific radiation syndrome as distinct from acute or chronic radiation disease which is a specific radiation syndrome. PMID- 2238610 TI - [A case of urticaria during carsil treatment]. PMID- 2238609 TI - [The therapeutic procedure in autoimmune thrombocytopenia in relation to the immunoglobulin specificity of the antithrombocytic autoantibodies]. AB - The author studied dependence of choice of therapeutic tactics on the immunoglobulin specificity of antithrombocytic autoantibodies in patients with idiopathic autoimmune thrombocytopenic purpura. It was found that in case of detection of antithrombocytic autoantibodies with a IgG specificity the patients are more sensitive to the treatment with glucocorticoids. In case of detection of IgM antithrombocytic autoantibodies, splenectomy at early stages of the disease is more effective. PMID- 2238611 TI - [Enterosorption in the treatment of patients with chronic urticaria]. AB - A synthetic carbon sorbent (SKNP-2) was included in the treatment of 197 patients with relapsing urticaria. Courses lasted 7, 14, 20 days. The clinical effect was favourable and its efficacy increased with prolongation of the therapy course time using the enterosorbent. Immunological parameters did not change in the course of treatment. PMID- 2238612 TI - [The correction of functional disorders of the cardiovascular system in patients with acute kidney failure treated by hemodialysis]. AB - A study is presented of the central hemodynamics in 38 patients with severe forms of acute renal failure of different genesis. Disorders were revealed related both to renal failure and use of active methods of extracorporal detoxication, namely, hemodialysis and hemosorption. Measures on the correction of disorders of the central hemodynamics are described. PMID- 2238613 TI - [The treatment of sexual disorders in men with autonomic dystonia]. AB - Results are reported of a study of 55 males with disorders of sexual potency with an objectively registered manifestation of vegetative dystonia. It was shown that sexual disorders in these patients have a psychogenic character. All of them showed neurosis and neurosis-like symptoms. With the purpose of finding effective treatment psychotherapy, phallic stimulation and physiotherapy were tried. Most effective was individual psychotherapy with elements of hypnotic suggestion and phallic vascular stimulation by local negative pressure. PMID- 2238614 TI - [The immunomorphological characteristics of prolonged exposure to the herbicide linuron]. AB - The authors investigated the effect of long-term use of the herbicide linuron on the histo- and ultrastructure of the thymus and factors of immunological defense. It was found that the use of linuron in animals resulted in development of secondary immunodeficiency states manifested in pathology of the thymic structure, first of all lesions of the epithelial cells-feeders and disorders of immunological indices. PMID- 2238615 TI - [Circulating immune complexes in workers in glass fiber-reinforced plastics manufacture]. AB - The authors examined 182 workers engaged in manufacturing of glass-reinforced plastics and revealed an increase of the level of circulating immune complexes and their content middle-molecular immune complexes. This makes it possible to suggest the pathogenetic role of circulating immune complexes in the development of allergic lesions in workers contacting with epoxide compounds. PMID- 2238616 TI - [Amiodarone--the current view of its therapeutic use]. PMID- 2238617 TI - [The current treatment of left-sided heart failure in acute myocardial infarct]. PMID- 2238618 TI - [The testicular biopsy--pro and contra]. PMID- 2238619 TI - [The carcinoembryonic antigen in chronic pancreatitis]. AB - The fasting carcinoembryonal antigen (CEA) concentrations in the serum and duodenal juice and after venous stimulation of the exocrine pancreas with the hormones CCK and secretin (Boots) were studied. Radioimmunologic test with a kit of the firm "Labimex"--PPR was used. 28 patients with clinically proved chronic pancreatitis and a control group of 27 healthy persons were examined. The fasting CEA serum concentrations in the patients with chronic pancreatitis were statistically significantly higher than those of the healthy persons--mean--16.5 ng/ml vs mean--8.2 ng/ml (p less than 0.001). In 14% of the healthy persons and 57% of of the patients with chronic pancreatitis the basic CEA concentrations were significantly increased. After stimulation with CCK and secretin the serum CEA concentration did not change substantially. The duodenal juice CEA concentrations after CCK and secretin stimulation were about 11 times higher than those in the serum--mean--113 ng/ml and mean--104 ng/ml for the control group vs mean--118 ng/ml and mean--110 ng/ml for the patients with chronic pancreatitis. No statistically significant difference between the patients with chronic pancreatitis and the control group of healthy persons was established. The results reveal the low specificity of the CEA as a "tumor marker". PMID- 2238620 TI - [The development of remission in patients with bronchial asthma]. AB - The efficacy of the therapeutic programs and rehabilitation measures for achievement of a permanent remission of bronchial asthma was studied in 436 patients, 18 to 71 years of age (mean age 45.3 years), 283 women and 153 men. In 42.89% of the patients the asthma was severe, in 47.07% it was moderate and in 10.09%--mild. 30.05% of the patients were with atopic asthma, 52.06%--with infectious dependence, 8.03%--with glucocorticoid deficiency and 2.98%--with hormonal imbalance. In all patients remission was achieved with a different reliability. Full remission was achieved in 24.08%, partial remission 1 degree- in 58.03% and partial remission II degree--in 17.89% of the patients. The duration of the remission varied from 2 up to 46 months. A remission longer than 6 months was achieved in 72.10% of the patients treated with intal or zaditen, in 61.36% of the patients treated with corticosteroids and only in 27.70% of the patients treated with symptomatic and general hygienic means. The duration and the quality of the remission depend on the correct selection of the therapy in the acute stage, the severity and the form of bronchial asthma. Better results are achieved in the mild form of bronchial asthma. The most frequent causes for destabilization of the remission were bronchopulmonary infections, incorrect reduction or discontinuing of the medication, formal supportive therapy, psychologic demobilization and irrational supportive therapy. PMID- 2238621 TI - [The diagnostic potentials of spatial velocity ECG in assessing the changes in ventricular depolarization]. AB - The study includes 702 patients (with left ventricular load, myocardial infarction and bundle branch block) and 130 healthy persons. To all these a spatial velocity EKG was made (SVEKG) as well as corrected orthogonal electro- and vectorcardiogram according to Frank, spatial ECG and standard EKG in 12 leads. The indices of the spatial velocity ECG were compared with those of the other methods on the basis of the criteria sensitivity and specificity. In the patients with right ventricular load the indices of the spatial electrocardiography showed the highest sensitivity; in the patients with left ventricular load and bundle branch block the indices of the corrected orthogonal electrocardiography showed the highest sensitivity. In the patients with myocardial infarction the potentials of several methods were equal. The insufficient number of investigations concerning the spatial velocity ECG cannot give a clear view of its potentials and its place in the clinical practice but some of its advantages make it very convenient for preparing a system of automatic analysis of the heart electrophysiological signal. PMID- 2238622 TI - [Doppler transmitral blood flow--a new method for assessing myocardial ischemia]. AB - A new method for interpretation of Doppler transmitral flow is presented. The peak of the early diastole is divided into two time intervals and the velocity of the rising and falling of this peak is determined. The method was applied in 31 patients with ischemic heart disease proved by coronarography and 30 healthy persons before and after bicycle ergometry [correction of veloergometric] load. Statistically significant changes of the parameters studied were found. These changes were compared with parallel changes in the electrocardiogram (12 standard leads). This led to the conclusion that Doppler transmitral flow is a more sensitive method for the diagnosis of myocardial ischemia than the electrocardiogram. PMID- 2238623 TI - [Lyme disease and the forms of its manifestation in Bulgaria]. AB - Two cases of serologically proved cardiac form of Lyme's disease are presented (for the first time in Bulgaria). An A-V block III degree was found in the first patient and an A-V block I degree in the second patient. The diagnosis is supported by epidemiologic data--endemic region, other patients with Lyme's disease, insects bite, season, etc. PMID- 2238624 TI - [Arterial pressure studies of the workers and employees of a textile plant]. AB - The results of a study of the arterial pressure of the workers and employees in a textile plant in Vratsa are presented and discussed. The frequency of hypertension is 16.32%, symptomatic hypertension--3.22%, borderline hypertension- 27.07%, hypotension--5.36%. Statistically significantly hypertension is more frequent in persons with a hereditary predisposition for arterial hypertension, are over 40 years of age and with overweight. The borderline hypertension becomes frequent after 50 years of age. Hypertension was not found statistically significantly more often in persons who work or had worked in conditions of professional noise above 85-105 decibels, are with higher education, psychic trauma, using more salt and smokers. Hereditary predisposition and overweight were equally frequent in the patients with renal hypertension and hypertension disease. The results support the conception that hypertension is a polygenic hereditary disease in the basis of which lies renal mechanism. PMID- 2238626 TI - [The early and late treatment results with azathioprine in Behcet's syndrome]. AB - Four patients (one man and 3 women) with generalized form of Behcet's syndrome with 3-7 years duration were followed up. Prior admission to the clinic the patients had been treated symptomatically, two of them with cyclophosphamide and one patient with corticosteroids without effect. In the clinic they were treated with Azathioprin 2 mg/kg body mass. At the end of the second month remission of the disease was registered in all four patients which lasts without discontinuing the treatment in one of the patients 7 years, in the second patient--4 years, in the third patient--3 years and in the fourth patient--2 years. The supporting treatment is 1 mg/kg body mass of Azathioprin which begins at the end of the first year after achieving a stable clinical remission. No side effects were observed. PMID- 2238625 TI - [Calcium-phosphorus metabolism and calcitrophic hormones in patients with active acromegaly with and without osteoporosis]. AB - Calcium-phosphor metabolism was studied in patients with active acromegaly with or without osteoporosis, mean age 45.2 +/- 11.4 years and mean duration of the basic disease 5.52 +/- 3.6 years. No significant deviations and no direct relation with the high serum growth hormone and prolactin levels were found. The normal basic secretion of the calcitrophic hormones--parathyroid hormone and calcitonin and their normal response to the hypercalcemia after intravenous calcium load of the patients with and without osteoporosis reject their direct participation in the pathogenesis of osteopenia. The changed skeletal sensitivity to calcitrophic hormones closely connected with the patients' age and the duration of the basic disease in combination with many other factors probably plays a major role in the pathogenesis of osteopenia. PMID- 2238627 TI - [Gordon's syndrome--a combination of hyperkalemia and arterial hypertension with preserved kidney function]. AB - A case of Gordon's syndrome in a 38 years old man is presented--hyperpotassemia and arterial hypertension with preserved renal function, normal supra-adrenal function, no data for hemolysis, normal coagulation state, mild compensated metabolic acidosis. Renal tubular defect, for excretion of potassium and chlorides, sodium reabsorption, tubular resistance to mineralocorticoids are discussed. The combination of hyperpotassemia and arterial hypertension might be due to phenotype manifestations of a single gene. PMID- 2238628 TI - [Autosomal recessive polycystic kidney]. AB - A case of a 22 years old woman with autosomal-recessive form of kidney polycystosis is presented. The diagnosis was made in early childhood. A combination of renal anomaly and hepatic fibrosis with manifestations of portal hypertension was present. No deviations from the other internal organs were found. At the age of 12 she entered into the stage of chronic renal failure. The last five years she is on dialysis treatment. She had survived several acute bleedings from esophageal varices. The authors are of the opinion that the case is of interest since patients with autosomal-recessive renal polycystosis very rarely reach majority. PMID- 2238629 TI - The clinical use of oral sulfonylureas in the management of non-insulin dependent diabetes mellitus (NIDDM). AB - Eighty percent of Americans afflicted with diabetes mellitus have Type II or non insulin dependent diabetes mellitus (NIDDM). Impaired or defective insulin secretion and insulin resistance are universal pathophysiologic findings. Management involves attention to diet, exercise, and commonly the use of insulin and/or oral sulfonylureas. Currently there are six marketed first and second generation agents available for use in the United States. Although the newer agents are more potent, they all share a similar mechanism of action. These agents can only be effective if the patient has retained beta cell secretory function. Pharmacokinetic and pharmacodynamic differences may make the newer agents, glyburide and glipizide, preferred in the management of Type II diabetes mellitus. The combined use of insulin and oral sulfonylureas may be useful for the patient exhibiting persistent fasting hyperglycemia despite maximal oral drug therapy. The precise role for combination therapy and optimal patient characteristics awaits further study. PMID- 2238630 TI - Magnesium deficiency. AB - Over the past 40 years, human magnesium deficiency has become recognized as a world-wide clinical problem. In 1926, Leroy (1), demonstrated the absolute need of magnesium for growth and life in mice, and the need for magnesium in plants was demonstrated in 1860. Although clinical deficiency was first reported in 1934, it was not until the 1950s that interest in clinical magnesium deficiency developed rapidly. Before the 1950s, textbooks of medicine, pediatrics and biochemistry did not mention magnesium disturbances. In this paper I shall emphasize the recognition and treatment of magnesium deficiency by giving details of the setting, i.e. illnesses, the multifaceted manifestations, the laboratory findings and safe protocols for treatment. PMID- 2238631 TI - Tort reform recommendations for West Virginia. AB - Tort reform is central to resolution of the malpractice issue in West Virginia. This article examines tort law and malpractice as viewed from federal and state levels and compares general liability costs in states. The article also looks at national trends in malpractice awards; at state initiatives in tort reform; and finally extracts what works and what doesn't. It presents strategies for legislative approaches to tort reform. PMID- 2238632 TI - Pectoralis major myocutaneous flap in reconstruction of head and neck defects. AB - Immediate reconstruction of head and neck defects due to various causes is required to restore structure, function, and appearance. The pectoralis major myocutaneous flap (PMMF) is the ideal reconstructive tissue for its accessibility, versatility, reliability, and cosmeticity. This paper reports a 10 year experience on the use of the PMMF for restoration of extensive head and neck defects. PMID- 2238633 TI - Lymphadenopathy in children: a concise review. AB - Lymphadenopathy is commonly found in sick children and the cause of the enlarged nodes is usually evident. However, lymphadenopathy of a prolonged duration or with larger than anticipated nodes often presents a diagnostic dilemma. Knowledge of the normal pattern of lymph node size in children and the mechanisms of lymphadenopathy are prerequisites to approaching the diagnosis. Historical and physical clues help to guide the diagnostic evaluation and may indicate the need for certain laboratory tests, a trial of antibiotics, immediate biopsy, or simply close observation. If a biopsy is performed, comprehensive evaluation of the lymph node is critical to the diagnosis and subsequent treatment. Although most children with peripheral adenopathy have reactive hyperplasia of unknown etiology, it is important to monitor children with persistent lymphadenopathy until a diagnosis is made or the adenopathy resolves. PMID- 2238635 TI - A new role. PMID- 2238634 TI - Just the facts, mam. PMID- 2238636 TI - This is still the United States of America. PMID- 2238637 TI - The confusion in obesity research standards. PMID- 2238638 TI - Patterns of symptomatology of adult women incest survivors. PMID- 2238639 TI - Scoliosis treatment effects on selected variables among adolescents. PMID- 2238640 TI - Value orientations of homeless men. PMID- 2238641 TI - Theoretical modeling to predict subjective well-being. PMID- 2238642 TI - Clinical colleagues as a source of data for faculty evaluation. PMID- 2238643 TI - Importance of expert judgment in content-related validity evidence. AB - The unified conceptualization of validity with regard to content-related evidence has been expressed succinctly by the authors of the Standards for Educational and Psychological Testing (AERA et al., 1985): Content-related evidence of validity is a central concern during [instrument] development, whether such development occurs in a research setting, in a publishing house, or in the context of professional practice. Expert professional judgment should play an integral part in developing the definition of what is to be measured, such as describing the universe of content, generating or selecting the content sample, and specifying the item format and scoring system. Thus, inferences about content are linked to [instrument] construction as well as to establishing evidence of validity after [an instrument] has been developed and chosen for use. (p. 11) This article has demonstrated the process of collecting content-related validity evidence in terms of the specific requirements of the Standards. Five standards were identified and interpreted according to the initial stages of instrument construction: domain specification, item development, and item, subscale, and scale content validation. The role of expert judgment during these stages and the variety of evidence that can be gathered were described. For most instruments, the review process would necessitate two meetings of 1 to 2 hours each to review the domain specifications and another two meetings to determine the match between the items and the specifications. The importance of these 8 hours or whatever additional time is needed to obtain the validity evidence was emphasized. Finally, an application of the Standards was provided to illustrate step-by-step how the judgmental review process can be planned and executed. PMID- 2238644 TI - A psychometric evaluation of a visual analogue scale of craving for cigarettes. PMID- 2238645 TI - Father's family violence and son's delinquency: conflict tactics, bonding, and serious juvenile crime in the Mexican-American family. PMID- 2238646 TI - Ethical similarities internationally. PMID- 2238648 TI - Collaboration for the development of a nursing diagnosis system. PMID- 2238647 TI - Longitudinal research--the challenge of maintaining continued involvement of participants. PMID- 2238649 TI - [Modification of physical fitness of patients with coronary heart disease with nifedipine during a stay at altitude]. AB - With this study including 9 patients with angiographically proven coronary heart disease it could be shown that a monotherapy with nifedipine in the galenic preparation as Adalat SL (Bayer AG, Leverkusen, FRG) is efficient in reducing myocardiac ischemia and concomitantly raising working capacity during bicycle ergometry as well after first time application of this drug as after continuous therapy with 1 tablet twice daily during 4 weeks. This findings are true both at normal environmental conditions (1000 ft above sea level) and at conditions of altitude induced hypoxia (9000 ft above sea level), simulated in a hypobaric chamber. There was no development of drug tolerance during continuous therapy with 1 tablet of Adalat SL twice a day. Out of these findings the conclusion can be drawn that in patients with coronary heart disease receiving protective therapy with Adalat SL there is no remarkably higher risk of episodes of angina pectoris or even myocardiac infarction at altitudes up to 9000 ft above sea level than is to be expected during daily life. PMID- 2238650 TI - [Mediastinal lymphadenectomy. Anatomical basis and its surgical relevance in central bronchus carcinoma]. AB - 102 patients with potentially curable bronchial carcinoma were subjected to pneumonectomy and mediastinal lymph node dissection regardless of gross appearance of the mediastinum at the time of surgery. 83 of these patients were analysed retrospectively. In 34 patients (41%) enlarged mediastinal lymph nodes were found; in 19 of these (56%) malignant invasion was verified histologically, whereas in 15 of these 34 patients (44%) the enlarged lymph nodes revealed only inflammatory changes. On the other hand, in 49 patients (59%) the mediastinum was grossly inconspicuous, yet in 2 of these patients (4.1%) microscopic invasion by carcinoma was found. This confirms that the assessment of the mediastinum by gross appearance is unreliable. As a consequence, mediastinal lymph node dissection should be performed routinely in all patients in order to detect occult metastases since only patients who had a complete resection have a change of cure. This approach is justified as in our experience mediastinal lymph node dissection does not impose an additional operative risk and long-term survival or even cure may be achieved in individual patients. Estimated 5-year survival in our patients with histologically proven mediastinal lymph node metastases was 22%; 3 of 21 patients with N 2 carcinoma are alive 8, 10 and 13 years p.o., without evidence of recurrence. The operative strategy and technical aspects based on anatomical knowledge of pathways of lymphatic spread of carcinoma of the lung are presented. PMID- 2238651 TI - [Significance of food allergens for the development of hyperreactive airway diseases]. AB - Food allergies may lead to local and systemic allergic reactions. Participation of respiration tract is rare and is only noticed in combination with additional systemic allergic reactions. Food allergies seem not to have influence on the origin of bronchial hyperreactivity or Asthma. Furthermore the question of genetic influence on the origin of children's allergies and possible preventive measures are discussed. PMID- 2238652 TI - [Relationship between pseudocroup and air pollutant burden of the inhaled air and weather]. AB - An epidemiological study is presented to demonstrate, in addition to the viral aetiology, the influence of airpollution and various weather conditions to the incidence of croup. By means of a special statistic tool (baseline data curves) we could demonstrate that rapid changes in airpollutants (especially NO and NO2) are followed by increased occurrence of croup. In addition, the quotient NO2/NO seems to correlate directly to the O3 concentration. The noticeable influence of airpollution as well as changing climatic conditions demonstrate the multiform aetiology of croup. PMID- 2238653 TI - [Relationship between pseudocroup and air pollutant burden of the inhaled air and weather--comment on the article by Dr. J.P. Guggenbichler]. PMID- 2238654 TI - CEA and CA 15-3 in primary and recurrent breast cancer. AB - To evaluate CA 15-3, a new breast cancer associated antigen, and to compare it with carcinoembryonic antigen (CEA), all patients presenting with breast cancer had preoperative and serial (3-monthly) postoperative levels measured. Of 124 patients with primary breast cancer, 23% had an elevated CA 15-3 (greater than 25 units/ml) while 11% had an elevated CEA (greater than 5 ng/ml) (p = not significant). Neither marker was an indicator of spread to regional lymph nodes in primary breast cancer. In 45 recurrences of breast cancer, CA 15-3 was elevated at the time of first recurrence in 58% while CEA was elevated in 47% (p = not significant). Of 17 patients with locoregional recurrence alone, none had a CA 15-3 above 40 units/ml while 11 of 12 with synchronous locoregional and distant recurrence had a CA 15-3 level greater than 40 units/ml (chi 2: 21.36, p less than 0.0001). This study shows that CA 15-3, like CEA, is of little clinical value in primary breast cancer. CA 15-3, however, is an accurate indicator (overall accuracy, 97%) of synchronous distant metastases in patients with locoregional recurrence from breast cancer. This information has important implications for further investigation and management of such patients. PMID- 2238655 TI - Changing trends in surgery for acute cholecystitis. AB - Surgery for acute cholecystitis has become the most frequent abdominal surgery in most hospitals, yet aspects of its management remain controversial. The aim of this study was to focus on the recent trends by demonstrating the principal differences between 2 series of patients operated on during 10-year intervals. Two hundred fifty-six consecutive operations for acute cholecystitis were performed from 1970 to 1977 (group O) and were compared to 260 cases operated from 1980 to 1987 (group N). Thirty-six variables were recorded in each case. All data obtained were computer recorded and analyzed. Several trends were observed in group N: 1. The population was significantly older with a higher proportion of males and diabetics. 2. There was a marked increase in common bile duct stones, acalculous cholecystitis, and gangrenous changes in the gallbladder. 3. There was a significant increase in patients operated on within 48 hours of admission. 4. There was a significant increase in the number of patients without previous history of biliary symptoms. 5. There was a significant decrease in the rate of wound infections and no statistically significant differences in mortality (N: 3.0%, O: 2.7%). 6. A decrease of the average postoperative hospital stay of 3.2 days was observed. In spite of the older and sicker population in group N, no significant increase in mortality occurred and the postoperative hospital stay was reduced. PMID- 2238657 TI - Dilatation of intrahepatic biliary strictures in patients with hepatolithiasis. AB - To investigate the role of balloon dilatation in the management of complicated hepatolithiasis with intrahepatic biliary stricture, 57 consecutive patients who received 208 sessions of dilatation in addition to the usual treatment were analyzed. The strictures were located in the right intrahepatic ducts (84.2%), left intrahepatic ducts (12.3%), or both (3.5%). Dilatation began 3-4 weeks after surgery. The routes of dilatation included the matured T-tube tract (3 cases), percutaneous transhepatic biliary drainage tracts (42 cases), and both (12 cases). The immediate overall success rate of complete stone clearance increased significantly from 0% predilatation to 94.7% postdilatation. The main complications of dilatation therapy consisted of septicemia (10.5%), hemobilia (10.5%), and mild diarrhea (80%). Eight patients (14%) with long-segment strictures received 11 postdilatation biliary stentings. Complications were 1 patient with occlusion and 2 patients with "spontaneous" hemobilia. Severe multiple strictures and coexistent secondary biliary cirrhosis were the contributing factors to complications. During the follow-up of 3.4 +/- 1.2 years, recurrence of strictures was found in 4 patients. Two of them belonged to the stenting group. The cumulative probability of restricture was low: 4% at 2 years, 6% at 2.5 years, and 8% at 3 years. We conclude that in complicated cases of hepatolithiasis with intrahepatic biliary stricture, dilatation and stenting are good adjuvant therapies. PMID- 2238658 TI - Previous abdominal colectomy affects functional results after ileal pouch-anal anastomosis. AB - We assessed the effect of previous abdominal colectomy on functional results after ileal "J" pouch-anal anastomosis (IPAA) in patients with ulcerative colitis. Twenty-five patients with colectomy prior to IPAA were compared with 22 patients who underwent noncolonic abdominal operations prior to IPAA. No differences were observed in pre- or postoperative resting anal sphincter pressure, squeeze pressure, or rectal inhibitory reflex. Previous colectomy was associated with a greater incidence of postoperative small bowel obstruction. Mean +/- SEM daily stool frequency at 1 and 12 months postoperatively, respectively, was 8.9 +/- 0.8 and 5.7 +/- 0.3 for patients who had undergone previous colectomy, and 8.2 +/- 0.7 and 6.0 +/- 0.5 for the no-previous colectomy group (p = not significant). At the same postoperative intervals, nocturnal stool frequency was 1.9 +/- 0.3 and 1.1 +/- 0.2 for the colectomy group and 1.5 +/- 0.3 and 0.6 +/- 0.1 for the no colectomy group (p = 0.05 at 1 year). More patients in the previous colectomy group had greater than or equal to 1 nocturnal stool after 1 year (71% versus 33%, p = 0.03). Although pouch capacity at 1 year was not different in the 2 groups, pouch capacity was directly related to stool frequency in the no colectomy group (r2 = 0.48, p = 0.01), but not in the previous colectomy group (r2 = 0.08, p = not significant). We conclude that previous abdominal colectomy may be associated with a higher overall incidence of small bowel obstruction. Moreover, previous colectomy is a determinant of postoperative nocturnal stool frequency after IPAA, most likely due to altered ileal pouch function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238659 TI - Neonatal necrotizing enterocolitis: experience with 100 consecutive surgical patients. AB - One hundred newborns with neonatal necrotizing enterocolitis (NEC) were treated surgically according to a uniform protocol between July, 1980 and June, 1988. The infants (53 females, 47 males) weighed between 600 and 3,800 g, averaging 1,500 g. Twenty-eight weighed less than or equal to 1,000 g, 38 weighed from 1,001 g to 1,500 g, and 34 weighed more than 1,500 g. Median age at the time of surgery was 14 days. Surgery was performed for pneumoperitoneum in 40, a "positive" paracentesis in 51, and for other reasons in 9 infants. A paracentesis was performed if intestinal gangrene was suspected clinically. Resection of gangrenous bowel with exteriorization was the usual procedure; in only 5 patients was primary closure performed. The hospital survival for the infants was 54% for the group weighing less than or equal to 1,000 g, 74% for the group weighing from 1,001 g to 1,500 g, and 79% for the group weighing more than 1,500 g. Overall hospital survival was 70%; it was 81% for those having a definitive procedure (excluding 14 infants with NEC "totalis"). There were 3 late deaths from causes unrelated to NEC. Significant long-term complications included failure-to-thrive in 23% and stricture formation in 30% of the survivors. Long-term follow-up showed gastrointestinal status to be normal in 74%; only 8% have persistent major gastrointestinal dysfunction. Mental and motor development was considered grossly normal in only 53% of the patients. PMID- 2238656 TI - Adenocarcinoma of the stomach: a review of 35 years and 1,710 cases. AB - The records of 1,710 patients with adenocarcinoma of the stomach treated at Charity Hospital over a 35-year period were reviewed to note any trends which might help in understanding the decreasing incidence and poor prognosis of the disease. The yearly number of gastric cancer patients has dropped from 234/100,000 in the 1950's to 195/100,000 in the 1960's to 108/100,000 patients in the last decade. The percentage of affected white males is decreasing at a rate equal to the increasing frequency of black female patients, while the ratios for black males and white females remain constant. The median age rose from 61.5 years to 66 years over the study period. The operability rate decreased from 82.4% to 72.8% and the resectability rate was 49%. Subtotal gastrectomy was the most common procedure, but radical subtotal gastrectomy gave the best 5-year survival. There are fewer lesions of the antrum today, but the highest number of 5-year survivors had antral lesions. Long-term survival of patients with lesions of the cardia improved from zero in the first 25 years to 14% in the last decade. For the last 2 decades, patients with stage III and IV lesions comprised one-half of the 5-year survivors. Our overall 5-year survival was 7.9%, but in the last decade it was 8.9%. Our 5-year survival for all patients who underwent a resection was 17.9%, but increased to 24.8% for the last decade. These improvements, in combination with a decrease in incidence, have dropped the overall mortality from gastric cancer. PMID- 2238660 TI - Cervical node metastases in early squamous cell carcinoma of the floor of the mouth: predictive value of multiple histopathologic parameters. AB - A semiquantitative assessment of multiple histological parameters was applied retrospectively to 66 patients with stage I and II squamous cell carcinoma of the floor of the mouth to determine if prognostic information relative to cervical node metastases could be obtained. Three parameters relating to the tumor cell population and 5 describing the tumor-host interface were evaluated on a point scale from 1 to 3 with the highest score going to the most threatening characteristic. Twenty of the 66 patients had either occult metastases identified by elective lymphadenectomy (n = 11) or developed metastases to the neck (n = 9). There was no correlation between traditional histological grading as recorded at the time of presentation and the frequency of cervical metastases (p greater than 0.05). Histological reevaluation defined 3 groups of patients with low (less than 14), moderate (14-16), and high scores (greater than 16) with an incidence of cervical metastases of 5/39 (12.8%), 6/17 (35.3%), and 9/10 (90%), respectively (p less than 0.001). The results suggest that microscopic grading could be a useful adjunct to the present TNM staging system in selecting patients likely to benefit from elective treatment of the neck. PMID- 2238661 TI - Multifactorial analysis of survival in primary extremity liposarcoma. AB - The treatment of extremity soft tissue sarcoma is now directed at limb preservation with the addition of various adjuvant therapies to improve treatment results. To achieve this goal, a knowledge of prognostic factors for extremity soft tissue sarcoma becomes increasingly critical. The object of this study was to analyze prognostic factors for survival in patients with extremity liposarcoma. Eighty-three patients with primary localized extremity liposarcoma, admitted from 1968 to 1978, were retrospectively reviewed. Surgical resection was the primary mode of treatment. Eleven prognostic factors were analyzed. Tumor factors included: histologic subtype, tumor grade, size, depth, invasion of vital structures, and site; operative factors included: type of operation, and surgical margins; and patient factors included: symptoms, age at diagnosis, and sex. Kaplan-Meier survival curves, and univariate and stratified log-rank tests of association were performed. Independent factors for predicting survival were identified using the Cox model stepwise regression technique. In univariate analysis of the entire group of patients, 5 factors were significant for tumor mortality: tumor grade (p = 0.00005), histologic subtype (p = 0.00025), tumor size greater than or equal to 5 cm (p = 0.005), type of surgery/margin (p = 0.0001), and invasion of vital structures (p = 0.008). When associations among all factors were analyzed, it was found that many factors were interdependent. The independent prognosticators were, therefore, determined according to the Cox model technique. For the multivariate analysis, well-differentiated and lipoblastic liposarcomas were excluded because of lack of survival variation within each group. The former group had no tumor-related deaths and the latter group showed 80% tumor mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238662 TI - Coloanal anastomosis after resection of low rectal cancer in the elderly. AB - Twenty-two patients had coloanal anastomoses performed after resection of low rectal tumors (16 adenocarcinomas and 6 large degenerated villous adenomas). The patients had an average age of 72 years (range: 62-85). A hand-sewn anastomosis was performed between a "J"-shaped colonic reservoir and the anal sphincter, except in 3 patients who underwent a straight end-to-end coloanal suture without pouch. A defunctionalized stoma was made in 18 cases. Mortality within 30 days of operation was 9%. Specific complications occurred in 2 patients (9%). Mean follow up in this series was 20.2 +/- 11.7 months (+/- standard deviation). Fifteen patients were alive and free of disease up to 54 months after surgery. One patient was found to have local recurrence at 19 months. The actuarial 3-year survival rate was 73% in the whole group (operative mortality included). Functional results were good in 16 of 19 patients, with an average 1.8-2.9 stools/24 hours and the continence rate was good. Three patients had complications requiring a permanent colostomy. From these preliminary results, coloanal anastomosis appears to be satisfying in regard to oncologic results and affords good anal function, even in the elderly patient (over 62 years of age). PMID- 2238663 TI - The "Kergin pneumonectomy". AB - Out of a series of 211 stage III (A and B) lung cancers radically resected with routine lymphadenectomy from 1971 to 1987, a total of 11 were squamous cell carcinomas invading the right main bronchus and lateral portion of the trachea. These patients were managed using a particular technique that we have always arbitrarily called, "Kergin pneumonectomy," after the Toronto surgeon who described it in 1952. These patients, today, are staged III B. There was no operative mortality and only 2 minor complications. Two patients survived 3 years and 1 is alive and free of disease 7 years from surgery. This technique should be considered before embarking on more perilous surgery such as "sleeve pneumonectomy," a procedure which still carries high mortality and morbidity rates and requires special equipment and intensive postoperative care. PMID- 2238664 TI - A new simple test for evaluation of intestinal bacteria. AB - We investigated a newly synthesized conjugate of ursodeoxycholic acid with para aminobenzoic acid (PABA) to determine its suitability to evaluate enteric bacteria. This compound, PABA-UDCA, is deconjugated by cholylglycine hydrolase to release free PABA whereas it is completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriological experiments, almost all of the microorganisms which split glycocholic acid deconjugated this compound. In animal experiments, urinary excretions of PABA were measured for 6 hours following oral administration of 10 mg PABA-UDCA. Ten control rats excreted 338.5 +/- 43.8 micrograms (mean +/- SD) of PABA; 10 rats with intestinal bacterial overgrowth due to enteric stagnant loops excreted more (673.6 +/- 222.1 micrograms; p less than 0.01), whereas 10 rats in each of 8 groups with intestinal antisepsis by oral administration of various antibiotics excreted significantly less (p less than 0.001) (ampicillin + doxycycline + fradiomycin: 18.3 +/- 16.7, polymixin B + tinidazole: 14.0 +/- 8.0, polymixin B: 224.9 +/- 74.3, tinidazole: 42.7 +/- 27.3, kanamycin: 50.3 +/- 18.2, clindamycin: 57.4 +/- 23.3, vancomycin: 70.4 +/- 27.0, and paromomycin: 160.4 +/- 51.9 micrograms). These observations indicate that this compound is likely to offer a simple and rapid method for evaluation of intestinal microorganisms without the use of radioisotopes or expensive, special apparatus. PMID- 2238665 TI - Suppression of the human mucosal-related colonic microflora with prophylactic parenteral and/or oral antibiotics. AB - The purpose of this investigation was to assess the effects of preoperative administration of parenteral antibiotics with or without concomitant preoperative administration of oral antibiotics on the colonic mucosal-related microflora. Thirty-one patients were studied in a prospective fashion. Group A patients (n = 8) had colonoscopic mucosal biopsies performed after mechanical bowel preparation. Group B patients (n = 5) received neomycin and erythromycin (NE), 1 g each following mechanical bowel preparation, at 1, 2, and 11 p.m. the evening prior to either elective colon resection (n = 2) or prior to colonoscopic biopsy (n = 3). Emergent trauma patients who had left colon or sigmoid perforations due to gunshot wounds requiring segmental resection comprised group C (n = 7). These patients received cefoxitin or cefotetan 2 g intravenously preoperatively. Individuals in group D (n = 11) all had elective left hemicolectomies or sigmoid resections due to nonobstructing malignancies. These patients underwent the same regimen as group B patients in addition to receiving intravenous cefoxitin perioperatively. Quantitative and qualitative bacterial cultures as well as scanning electron microscopy (SEM) were used to study the mucosa-associated flora. Tissue for culture and SEM were obtained from the pathologic specimen immediately after removal. The interval between the dosage of parenteral antibiotics to tissue removal was 3 hours in both groups. Anaerobic and aerobic counts were suppressed the greatest in patients receiving both oral and parenteral antibiotics (p = 0.0001). Mean anaerobic counts decreased from 3.4 X 10(7) in group A to 1.8 X 10(2) (mean cfu/g) in group D patients. Mean aerobic counts in group A decreased from 3.7 X 10(6) to 64 (mean cfu/g) in group D.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238666 TI - Pylorus-preserving duodenopancreatectomy: long-term complications and comparison with the Whipple procedure. AB - We have performed 33 pylorus-preserving duodenopancreatectomies. Twenty patients presented with severe chronic pancreatitis and 13 with periampullary adenocarcinoma. We have no postoperative mortality and a 24% rate of morbidity. Complications include anastomotic leaks (2), surgical bleeding (1), anastomotic ulceration (1), and others (4). We have complete follow-up for all cases. In the tumor group, 8 (62%) patients are alive with a mean survival time of 20 months (range: 2-46). In the pancreatitis series, all patients are alive after a mean of 34 months (range: 4-66). We have observed 5 cases (15%) of anastomotic ulcerations responsible for stenosis (2) and acute perforation with peritonitis (2) occurring after a mean interval of 18 months. Four cases have been confirmed histologically after resection. The short- and long-term beneficial effects of the pylorus-preserving operation on patient well-being and nutritional status were confirmed and compared with the results achieved after a Whipple procedure performed in a series of 18 consecutive patients. PMID- 2238668 TI - West Germany: still an underdeveloped country in the diagnosis and early treatment of primary hyperparathyroidism? AB - Early diagnosis of asymptomatic patients with primary hyperparathyroidism (primary HPT) has been achieved in Scandinavia, the United States of America, and the United Kingdom during the last 20 years. Comparable results have been reported from some medical centers from West Germany; however, clinical manifestations were pronounced and patient symptoms were high in our population with primary HPT (N = 128) operated on at the University of Dusseldorf from April, 1986 to July, 1989. Only 19 patients (14.8%) were asymptomatic while the others suffered from nephrolithiasis (39%), osteopathy (32%), gastrointestinal disturbances (28.9%), and depression (11.7%). In 46 (35.9%) of our patients, the duration of these clinical symptoms exceeded 10 years, in 27 patients (21%) 15 years, and in 12 patients (9.3%) even 25 years. We, therefore, conclude that primary HPT is still a grossly underdiagnosed illness in parts of West Germany, presently, with patients suffering from severe clinical symptoms for more than 1 2 decades before definitive treatment. PMID- 2238667 TI - Evaluation of effectiveness of mass screening for colorectal cancer. AB - As the first step in the epidemiological evaluation of the effectiveness of mass screening for colorectal cancer, we compared clinicopathological features and survival rates of patients with cancer detected by mass screening (screened group) with those for patients treated in our outpatient clinic in the same period (outpatient group). The screened group consisted of 53 patients with colorectal cancer detected by 2-day or 3-day screening for fecal occult blood by guaiac slides. Their background factors were comparable to those of 120 patients of the outpatient group in regard to age, sex ratio, location of cancer, and histological type of cancer. In the screened group, 90% of patients had no complaints, and positive occult blood tests led to the detection of cancers. More than 60% of the patients had Dukes' A and B1 early cancers while only about 30% had advanced cancers. In the outpatient group, nearly 90% of patients were symptomatic, most commonly from rectal bleeding. Early-stage cancers made up only 20%, and large, advanced-stage cancers accounted for 80%. The 5-year survival rate of the screened group was 91.5%, being significantly higher than the 60% survival rate for the outpatient group. It is anticipated that mass screening for colorectal cancer by guaiac fecal occult blood testing will significantly reduce the mortality due to this neoplasm. PMID- 2238669 TI - Acquired and congenital clotting syndromes. AB - Although Virchow postulated 100 years ago that hypercoagulability states exist, it has only been in recent years that methods of documenting hypercoagulability have been developed. These clotting tendencies can be acquired or congenital. The common causes of acquired clotting tendencies include conditions which result in tissue and cellular damage, shock, transfusion reactions, and tissue necrosis. Certain drugs and drug reactions, and certain disease states which include blood dyscrasias and cancer are also associated with clotting problems. In certain diseases such as homocystinuria, hyperlipidemia, and lupus erythematosus, abnormal clotting tendencies may also develop. Important advances in the recognition of hypercoagulability have come with the documentation that congenital clotting abnormalities exist. Moreover, these abnormalities are proving to be more common than are congenital bleeding syndromes. Patients who appear to have spontaneous clotting manifestations and are under 40 years of age should be screened for one of these abnormalities. These congenital clotting tendencies can be classified as defects in thrombosis inhibitors, dysfibrinogenemias, or defects in fibrinolysis. The first thrombotic inhibitor defect recognized was antithrombin III deficiency which was reported in 1965. Subsequently, Protein C, Protein S, and Heparin cofactor II deficiencies have been recognized as contributing to thrombotic tendencies. Dysfibrinogenemias are relatively rare and most are associated with bleeding problems; however, 11% of the abnormal fibrinogens are associated with a clotting tendency. The reason appears to be that these fibrins are resistant to fibrinolysis. The most common defects which are associated with thrombotic tendencies appear, at the present time, to be due to defects in fibrinolysis. These include hypoplasminogenemia, decreases in plasminogen activator, increases in plasminogen activator inhibitor, and Factor XII deficiency. PMID- 2238671 TI - Use of plasminogen activators in venous thrombosis. AB - A major advance in the treatment of thrombosis has been the development of thrombolytic agents. Streptokinase and urokinase have been the standard agents available for many years, but in recent years the most exciting change in the field has been the development of a new generation of plasminogen activators, the principal one being tissue plasminogen activator. The first generation of plasminogen activators--streptokinase and urokinase--do not have fibrin specificity and predictably induce plasma proteolysis when administered systemically in doses which introduce thrombolysis. The second generation of plasminogen activators are much more fibrin-specific and offer a promise of fewer complications. In a number of major randomized studies, these thrombolytic agents have proved effective clinically. The major complication of thrombolytic therapy, however, is hemorrhage. The risk of hemorrhage increases with the length of infusion and occurs most often from sites of vascular invasion such as needle punctures or cutdown sites from surgical wounds. This can be treated by applying pressure over the wound and discontinuing the thrombolytic agent whose half-life is measured in hours. It is believed that as more experience is acquired with the second-generation plasminogen activators, better control of these drugs will result in fewer complications and more effective and wider application of therapy. PMID- 2238670 TI - Diagnosis of deep vein thrombosis. AB - A wide range of clinical symptoms and signs are observed with venous thrombosis. Nonetheless, clinical diagnosis has been found to be unreliable and accurate diagnostic methods must be used before potent therapy such as anticoagulation is instituted, since the complications of treatment themselves can be life threatening. Phlebography is still the basic reference for evaluation of deep venous disease. While it is felt to be the most accurate, there are still limitations relative to difficulty in separating acute from chronic disease, and in obtaining adequate contrast in certain veins such as calf muscles and in the larger intraabdominal veins. Moreover, it is an uncomfortable invasive test, not without complications of its own. The 125I-fibrinogen uptake test is an excellent test for screening for forming thrombi. The sensitivity of this test is high, particularly in the detection of small calf vein thrombi. The primary drawbacks of this technique are that it is falsely positive in cases where there has been bleeding, inflammation, gross edema, arthritis, or leg ulceration. It is not accurate above mid-thigh because of the high blood flow at the level of the groin and pelvis. Radioactive labeled plasmin which will adhere to the surface of recently formed thrombi can also be used for diagnosis. The limitations are a very short half-life of the radioactive label so that repeated investigation of a patient cannot be performed unless new injections are given. The diagnostic accuracy is comparable to that of radioactive labeled fibrinogen and has the same advantages and disadvantages. Plethysmographic techniques have been used with various modifications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238673 TI - Development of the postthrombotic syndrome: its management at different stages. AB - The postthrombotic syndrome consists of clinical features which follow thrombosis of deep venous return of the limb. Patterns of postthrombotic changes remain difficult to predict and once established, difficult to contain and reverse. Following a thrombotic event of the lower limb, 3 clinical stages can be observed which may be followed by intervening quiescent intervals. Stage I, or the early phase, is characterized by the residual obstructive process following acute venous occlusion. This can be manifested by either a bursting type of pain (venous claudication) or edema of the leg. A thrombotic process can involve the calf veins, thigh veins, pelvic veins, or any combination of the three. Specific clinical syndromes develop depending on the venous pump system involved. The venous pump system consists of the plantar calf pump and the thigh pump. These serve to propel blood upward. Involvement of any one or more of the 3 in the thrombotic processes can result in a relative obstruction with a specific pattern of clinical symptoms. Optimally, the venous thrombotic process should be treated during this early phase to prevent the subsequent events which may render the process irreversible. The second stage of the postthrombotic syndrome consists of the development of fat sclerosis. At this stage, the process becomes progressively irreversible as the extravasation of fibrin into the interstitial space results in progressive fibrosis and sclerosis. This results in damage to the skin and subcutaneous tissues which render the process irreversible. Specific treatment, while still introducible at this stage, can halt the progress of the syndrome, but rarely results in complete reversal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238674 TI - Military surgeons as internationalists. PMID- 2238675 TI - History, culture and health care. PMID- 2238676 TI - HMOs are not the answer. PMID- 2238677 TI - Making certain that children are immunized. PMID- 2238672 TI - Surgical treatment of acute deep venous thrombosis. AB - In patients with venous thrombotic disease and in whom anticoagulation or thrombolytic therapy is inappropriate, ineffective, or even contraindicated, insertion of vena caval filters or venous thrombectomy must be considered. The primary indication for the placement of vena caval filters is in patients who have developed a pulmonary embolus and in whom anticoagulation is either contraindicated or in whom anticoagulation must be discontinued because of the development of bleeding complications. At the present time, either the Greenfield filter placed through a jugular, femoral, or axillary venotomy or the bird's nest filter are appropriate and appear to be the most effective and least fraught with complications. The use of venous thrombectomy has waxed and waned over the last several decades. At the present time, the procedure is advocated mainly for lower limb venous thrombosis which is extensive enough to threaten limb viability. On occasion, it may be appropriate to extend the indications for venous thrombectomy to include femoral thrombosis of less than 10 days duration or iliac thrombosis of less than 3 weeks duration with floating thrombi at the level. Technical modifications which improve the patency of the obliterated veins which are predisposed to rethrombosis include the creation of a temporary arteriovenous fistula and meticulous care in removing the entire clot. The patient should be treated with anticoagulants postoperatively to prevent a recurrence of the problem. The main theoretical advantage of venous thrombectomy is a reduced incidence of postthrombotic syndrome. Objective data to support this contention do not exist. PMID- 2238678 TI - Tears. PMID- 2238679 TI - Hunting-related injuries. AB - One hundred four patients treated for injuries incurred while hunting were prospectively studied during two consecutive fall seasons. A questionnaire was completed at initial evaluation and hospital records were subsequently reviewed. One hundred (98%) patients were male. Patient ages ranged from 10 to 78 years (median = 32 years). Mechanism of injury included knife or arrow penetrations (25), firearm wounds (12), falls (17), overexertion (5), and misadventures with hazards (40). Soft tissue, maxillofacial and orthopedic injuries predominated. Four patients experienced cardiac events. Hypothermia was noted in three, and animal-related injuries occurred in five. Eighteen (17%) patients were hospitalized. Serious injury was evident in 34 (33%). There were no deaths. Outpatient follow-up was necessary in 90%. Mishaps most frequently occurred because of overexcitement, unfamiliarity with equipment, or carelessness. Alcohol and drug use were only rarely identified. Almost one half of patients were injured during the 9-day gun deer hunting season. A wide variety of injuries occur during hunting activities. While many are minor, serious morbidity with potential long-term disability may result. Costs in time and money may be substantial. Simple measures could prevent many hunting-related mishaps. PMID- 2238680 TI - Magnesium metabolism. AB - Magnesium is the second most abundant intracellular cation in the human body and is necessary as a cofactor in more than 300 enzymatic reactions. The generation and use of adenosine triphosphate is dependent on the presence of magnesium. The assessment of the magnesium status of a patient is problematic because there are no easily performed tests that reliably predict the intracellular concentration. There are recognized molecular and cellular actions of magnesium that explain clinically recognizable problems when a magnesium deficiency or excess is present. Guidelines for therapy of magnesium deficiency are given. Future directions in research are given. PMID- 2238681 TI - I-123 Iofetamine SPECT scan in children with neurological disorders. AB - I-123 Iofetamine (IMP) single photon emission computed tomography (SPECT) imaging of the brain in 42 patients (ages 14 days to 23 years) was compared with other localizing studies in children with neurological diseases. All had an EEG and at least one imaging study of the brain (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Seventy-eight percent of the patients had an EEG within 24-72 hours of the IMP-SPECT scan. Thirty-five (83%) had a history of seizures, and the remainder had other neurological conditions without a history of seizures. In most cases, a normal EEG reading with normal CT or MRI result predicted a normal SPECT study. When the EEG was abnormal the majority of the IMP SPECT scans were abnormal and localized the abnormality to the same region. A comparison with CT and MRI showed that structural abnormalities involving the cortex were usually well demonstrated with IMP-SPECT imaging. Structural lesions confined to the white matter were generally not detectable with IMP-SPECT. In a few cases, SPECT scans revealed abnormalities in deep brain areas not identified by EEG. IMP-SPECT imaging is a valuable technique for the detection and localization of abnormal cerebral metabolic activity in children with seizure disorders. A correlation with CT or MRI is essential for proper interpretation of abnormalities detected with IMP SPECT imaging. PMID- 2238682 TI - Cruzan: a clinician's response. PMID- 2238683 TI - Power of attorney for health care. PMID- 2238684 TI - Self-reported barriers to mammography: implications for physicians. PMID- 2238685 TI - Why have our patients lost faith in us? PMID- 2238687 TI - Coronary reconstruction in a patient with patent double Vineberg implants and subclavian stenosis. PMID- 2238686 TI - Patterns of red blood cell use in southeastern Wisconsin. AB - We conducted a retrospective study of red blood cell use in southeastern Wisconsin to characterize transfusion practices and provide data for designing educational programs. Charts of 533 patients who received 3,006 units of blood at ten hospitals were reviewed. Demographic, diagnostic, surgical, and laboratory data and indications for transfusion were obtained. Mean blood use per patient (U/pt) was 5.6, 7.2, and 4.1 units for all patients, surgical and non-surgical, respectively. Fifty percent of the patients underwent surgery, used 64% of the blood, and required more postoperatively (4.2 U/pt) than intraoperatively (2.8 U/pt). Open-heart surgeries required 32% of all blood. Eighty-two percent of postoperative transfusions occurred when the hematocrit was less than or equal to 30%. Only 2.8% of eligible elective surgery patients made pre-deposit autologous donations and contributed 1% of the total blood used. PMID- 2238688 TI - New federal hospital patient transfer requirements. PMID- 2238689 TI - Can we influence adolescent health behavior? PMID- 2238691 TI - Wisconsin's Clean Indoor Air Act: an overview. PMID- 2238690 TI - The Wisconsin mammography quality assurance program. PMID- 2238692 TI - Environmental epidemiology. PMID- 2238693 TI - Indoor air pollution in developing countries. AB - Of the four principal categories of indoor pollution (combustion products, chemicals, radon and biologicals), research in developing countries has focused on combustion-generated pollutants, and principally those from solid-fuel-fired cooking and heating stoves. Such stoves are used in more than half the world's households and have been shown in many locations to produce high indoor concentrations of particulates, carbon monoxide and other combustion-related pollutants. Although the proportion of all such household stoves that are used in poorly ventilated situations is uncertain, the total population exposed to excessive concentrations is potentially high, probably several hundred million. A number of studies were carried out in the 1980s to discover the health effects of such stove exposures. The majority of such studies were done in South Asia in homes burning biomass fuels or in China with coal-burning homes, although a sprinkling of studies examining biomass-burning have been done in Oceania, Latin America and Africa. Of the health effects that might be expected from such exposures, little, if any, work seems to have been done on low birthweight and eye problems, although there are anecdotal accounts making the connection. Decreased lung function has been noted in Nepali women reporting more time spent near the stove as it has for Chinese women using coal stoves as compared to those using gas stoves. Respiratory distress symptoms have been associated with use of smoky fuels in West India, Ladakh and in several Chinese studies among different age groups, some with large population samples. Acute respiratory infection in children, one of the chief causes of infant and childhood mortality, has been associated with Nepali household-smoke exposures. Studies of chronic disease endpoints are difficult because of the need to construct exposure histories over long periods. Nevertheless, chronic obstructive lung disease has been associated with the daily time spent near the stove for Nepali women and found to be elevated among coal-stove users compared to gas-stove users in Shanghai. In contrast to early reports, there seems to be little or no risk of nasopharyngeal cancer from cookstove smoke. Several studies in China, however, have found smoke to be a strong risk factor for lung cancer among non-smoking women. In addition, severe fluorosis has been observed in several parts of China where coal fluoride levels are high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238694 TI - Acute pesticide poisoning: a major global health problem. AB - The global problem of acute pesticide poisoning has been confirmed as extensive by a variety of independent estimates. Further, it is also recognized to be a problem confined to the developing countries. Most estimates concerning the extent of acute pesticide poisoning have been based on data from hospital admissions which would include only the more serious cases. The latest estimate by a WHO task group indicates that there may be 1 million serious unintentional poisonings each year and in addition 2 million people hospitalized for suicide attempts with pesticides. This necessarily reflects only a fraction of the real problem. On the basis of a survey of self-reported minor poisoning carried out in the Asian region, it is estimated that there could be as many as 25 million agricultural workers in the developing world suffering an episode of poisoning each year. This article emphasizes the need to control the problem on a collaborative basis by all concerned, including national governments, agrochemical industries, international agencies, scientists and victims. PMID- 2238695 TI - Assessing the health impact of urbanization. AB - Several components of urbanization influence health status, but it is difficult to attribute changes in health status to any particular component. The overall impact may be estimated by relating the degree of urbanization of populations to some proxy measure, like the under-5 mortality rates. In this respect the net effect of urbanization is shown to be beneficial. A variety of survey and computational methods have been used to clarify the relationship. Some illustrate the effects of urbanization upon particular clinical conditions, such as promoting the eradication of leprosy, others of particular components, such as overcrowding and pollution, on infant mortality. To help set goals, excess or avoidable mortality may be computed for a country or region by relating its experience to current mortality levels in a developed country; and changes in the levels of avoidable mortality from sentinel conditions such as infectious diseases may be related to changes in particular aspects of urbanization, e.g. improvements in levels of sanitation. Migration to the urban environment imparts the tendency to acquire the health characteristics of the host population. Rapid urbanization causes problems of psychosocial adjustment for older children. Urbanization may impact upon the incidence and prevalence of disability. Where sex-age disability-survey data exist, they may be combined with age-specific mortality data to construct an index of disability-free life expectancy, a more subtle measure for assessing the progressive impact of urbanization. Up to now, however, there have been no international studies of how levels of disability change according to the progress of urbanization, and there are no international census or survey recommendations for harmonizing the classification of disabled people.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238696 TI - Urban air pollution in Latin America and the Caribbean: health perspectives. AB - In the last few years, air pollution has become a major issue in some countries of Latin America and the Caribbean because of urban development and growing industrialization. In addition to industrial processes often concentrated in the cities, vehicle emission and stationary-source fuel combustion are the primary sources of air pollution. Although air-quality standards have been established in some Latin American countries, these are frequently exceeded. Adverse health effects of air pollution have been mainly associated with the following pollutants: sulfur dioxide and particulate matter, photochemical oxidants, nitrogen dioxide and carbon monoxide, and lead. Short-term as well as long-term effects can be expected at levels exceeding WHO guidelines. The Latin American urban areas most affected by anthropogenic pollutant emissions are: the area of Sao Paulo (Brazil), the city of Santiago (Chile) and the metropolitan area of Mexico City. However, situations similar to those prevailing in these cities could well occur in other cities of Latin America and the Caribbean. The population exposed to air-pollutant levels exceeding WHO guidelines can be estimated to 81 million or 26.5% of the total urban population of Latin America and 19% of its total population. These estimates correspond to 30 million children (0-14), 47 million adults (15-59) and 4 million elderly people (60+). To date a very limited number of epidemiological studies have been carried out to determine the potential health effects of air pollutants in Latin America. To obtain a rough estimate, a scenario was hypothesized in which subjects living in cities would be exposed to a given level of air pollutant, using data from the international literature to extrapolate the expected number of events in different strata of the hypothetical population. The estimated health effects are considerable and warrant priority control intervention. This is true although epidemiological studies are needed to evaluate the health impact of specific pollutant compounds as well as their interactions in Latin American populations exposed to high levels of pollution. PMID- 2238697 TI - Lead in petrol: the mistake of the XXth century. AB - The health aspects of the use of lead in petrol were evaluated in the 1920s in the United States of America and, in spite of warnings from certain lead-toxicity experts, lead addition to petrol became standard international practice. Available data now show that lead in petrol at the scale of use in the 1970s produced significant environmental lead contamination and increased average blood lead levels in the general population. National sample surveys of blood-lead levels in the United States carried out annually from 1976 show a decreasing trend closely correlated with the use of lead in petrol. Recent longitudinal epidemiological studies have concluded that the exposure levels associated with lead in petrol can cause a reduced average mental ability in children. These studies accounted for the potential confounding from socioeconomic and other factors. The practical conclusion from the studies reviewed is that there should be as little human lead exposure as possible, because there may be no threshold for the effects occurring and many thousand children have already been affected in the United States and other countries. The environmental health calamity caused by lead in petrol could have been avoided if the initial warnings had been heeded and better preliminary research of the health issues had been carried out. Nevertheless, incontrovertible proof of causality should not be required before regulations are made to protect public health. PMID- 2238698 TI - Health risks associated with pollution of coastal bathing waters. AB - A number of bacterial, viral and other diseases can be contracted by man through exposure to sewage-polluted bathing-water or beach sand. The increasing use of the sea for recreation has led to major concern regarding health hazards to both local and tourist populations. Epidemiological studies attempting to correlate microbiological water quality with health effects have produced different results, leading to a wide variation in recreational water quality criteria and standards applied, and to considerable controversy regarding their implementation. The Mediterranean provides a good example of a problem region where health risks are accentuated as a result of high utilization of bathing areas coupled with long exposure periods. Coastal pollution by sewage is still a major concern and control measures vary considerably. A number of microbiological/epidemiological studies have been carried out since 1953 in an attempt to define the levels of risk following exposure to different concentrations of bacteria in bathing waters. Most of these have been prospective studies whose design involved subject recruitment on the beach itself, classification of swimmers on the basis of immersion of the head in the water, and follow-up interviews after 7-10 days, together with a system for validation of gastrointestinal symptomatology. Practically all studies showed higher morbidity among bathers as compared to non-bathers, but correlation between specific symptoms and bacterial indicator concentrations varied considerably. On the basis of the 1972-1978 Cabelli Environmental Protection Agency (EPA) study in the United States of America, later developed by EPA into a recommended health effects criterion for marine recreational waters, one would expect 25-40 gastrointestinal cases per 1,000 persons exposed to seawater containing 100 enterococci per 100 ml. Extrapolation of these figures to annual bathing populations indicates the potential magnitude of the problem. Much more work is needed however before a satisfactory dose-response relationship is obtained, principally because of confounding factors inherent in all studies carried out so far, which still require a solution. PMID- 2238699 TI - The role of environmental and occupational hazards in the adult health transition. AB - In the course of economic development from the pre-industrial to the post industrial stages, human communities go through major social and economic transitions. The demographic transition, a long established concept, refers to the change from a stage of high birth rates and mortality rates to one of low birth rates and mortality rates. The mortality rates have always decreased before the birth rates, giving rise to a period of rapid population growth in each society. The recently-coined term "health transition" provides a more detailed view of the different aspects of the mortality decline and of the changes in morbidity and causes of morbidity which also accompany economic development. The health transition is associated with major changes in exposure to environmental and occupational health hazards. The traditional hazards of the pre-industrial stage include unsafe drinking-water, poor sanitation, infected food, tropical disease vectors, indoor air pollution from biomass smoke, and accidents in agriculture and fishing. Gradually these are replaced by or overlap with the modern hazards, such as urban air pollution, tobacco smoking, pesticides, occupational hazards in new industries and traffic accidents. The health impact of these hazards depends very much on the preventive measures taken. For some hazards there is an increasing health risk, in parallel with the increasing occurrence of the hazard, which is followed by a decreasing health risk as preventive actions become effective. This intervention transition does not occur automatically with economic development, but requires specific policies and plans, as well as community involvement. The adult age group (15-59 years) is likely to be at particular risk for environmental and occupational hazards which emerge during the health transition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238700 TI - Isolation of urinary p-hydroxylated metabolites of mephentermine and phentermine in male Wistar rats. AB - 1. p-Hydroxymephentermine (p-hydroxy-MP) and p-hydroxyphentermine (p-hydroxy-Ph) were isolated as hydrochlorides from urine of male Wistar rats repeatedly dosed with mephentermine (MP). In addition, p-hydroxy-Ph was isolated as the hydrochloride from urine of the rats dosed with phentermine (Ph). 2. These results substantiate previous indications that p-hydroxylation of MP and Ph was a primary metabolic reaction in the rat. PMID- 2238701 TI - Development of a 19F-n.m.r. method for studies on the in vivo and in vitro metabolism of 2-fluoroaniline. AB - 1. A 19F-n.m.r. method has been developed for study of the metabolism of 2 fluoroaniline both after in vivo exposure of rats and in in vitro model systems. 2. From the 19F-n.m.r. spectrum of the 24 h urine it was calculated that over 90% of the dose was excreted within 24 h. The metabolic pattern showed that 85% of the metabolites were para-hydroxylated, 72% sulphated, 13% glucuronidated and 29% N-acetylated, 4-amino-3-fluorophenyl sulphate being the main urinary metabolite (53%). 3. In vitro studies of phase I metabolism of 2-fluoroaniline with rat liver microsomes was representative for the in vivo metabolism as hydroxylation in both systems was observed only at the para-position. 4. Phase I+II metabolism was studied in vitro in either isolated rat hepatocytes in suspension or in a 1 h recirculating liver perfusion system. In both these in vitro systems para hydroxylation, N-acetylation, sulphation and glucuronidation of 2-fluoroaniline were observed. The ratio between glucuronidation and sulphation was dependent on sulphate availability. 5. Of the in vitro systems tested, hepatocytes in Krebs Ringer (sulphate limited) medium was the best model for in vivo metabolism. 6. The detection limit for fluoro-containing metabolites in this 19F-n.m.r. method was 1 MicroM for an overnight run using a Bruker CXP 300 spectrometer. From this it can be concluded that 19F-n.m.r. urine analysis is a useful tool in biomonitoring studies. For 2-fluoroaniline the method appears to be more sensitive than currently available h.p.l.c./t.l.c. methods. In addition, concentration of urine samples can result in either lower detection limits, or in shorter times needed for n.m.r. data acquisition. 7. N-acetylation is known to show genetic polymorphism. Therefore, the 19F-n.m.r. method, detecting all 2 fluoroaniline metabolites, has the additional advantage of eliminating the risk of obtaining false negatives for fast acetylators. PMID- 2238702 TI - Metabolism of illudin S, a toxic principle of Lampteromyces japonicus, by rat liver. I. Isolation and identification of cyclopropane ring-cleavage metabolites. AB - 1. Illudin S, a toxic principle of the basidiomycete Lampteromyces japonicus, was incubated with rat liver 9000 g supernatant and its metabolites studied. 2. Two metabolites, M1 and M2, were isolated and identified as cyclopropane ring cleavage compounds by n.m.r., i.r. and mass spectral analyses. Moreover, M2 contained a chlorine atom. 3. On the basis of detailed analyses of the 2D n.m.r. spectra and differential nuclear Overhauser effect experiments, the previous assignments of the cyclopropane carbons of illudin S were revised. PMID- 2238703 TI - Species differences in metabolism of codeine: urinary excretion of codeine glucuronide, morphine-3-glucuronide and morphine-6-glucuronide in mice, rats, guinea pigs and rabbits. AB - 1. Metabolites of codeine were determined by use of h.p.l.c. in urine of male mice, rats, guinea pigs and rabbits injected with 10 mg codeine/kg subcutaneously. 2. In 24 h urines of these species, unchanged codeine, codeine glucuronide, free morphine, and morphine-3-glucuronide were as follows: mice, 6.8, 1.6, 0.8 and 7.6% dose; rats, 1.6, 0.2, 4.3 and 23.9% dose; guinea pigs, 1.6, 39.8, 0.2 and 1.6% dose; rabbits, 2.2, 24.5, 1.3 and 17.9% dose. Urinary excretion of morphine-6-glucuronide was 0.7% dose in guinea pigs, 1.9% in rabbits, and not detectable in mice and rats. Norcodeine was found only in the urine of mice. 3. These results indicate that codeine is metabolized in all four species by glucuronidation and by oxidative N- and O-demethylation, but the quantitative excretions of metabolites were quite different in different species. PMID- 2238704 TI - Flumecinol, a novel inducer of testosterone 16 alpha-hydroxylation in male rats. AB - 1. Flumecinol, a new inducer of the cytochrome P-450 monooxygenases, was studied in rats as a possible effector of liver microsomal testosterone oxidases. The drug enhanced the total content of liver cytochrome P-450 in immature and adult rats. 2. When total testosterone oxidation activity was compared in liver microsomes of treated and untreated rats, no differences in activities were observed in 60-day-old-rats, but a slight decrease was found in 35-day-old treated rats. 3. Several regio- and stereo-specific hydroxylases were modified by flumecinol administration; in 35-day-old rats only 16 alpha-hydroxylation was induced, whereas in 60-day-old rats a slight increase in 2 alpha-hydroxylation was also observed. PMID- 2238705 TI - Studies on the cytochrome P-450 of avocado (Persea [corrected] americana) mesocarp microsomal fraction. AB - 1. Because of the low concentration of cytochrome P-450 in avocado fruit, microsomal fractions were prepared using polyethylene glycol aggregation and low speed centrifugation, thus avoiding the need for high-speed centrifugation of large volumes of post-mitochondrial supernatant. Recoveries of cytochrome P-450 by this means (0.29 nmol/g tissue) were similar to those after the usual high speed centrifugation preparation (0.26 nmol/g). The cytochrome P-450 content of tulip bulb (0.30 nmol/g) was similar to that of avocado, but both plant tissues had much lower P-450 contents than did rat liver (13.0 nmol/g). 2. Spectral studies indicate that cytochrome P-450 of avocado mesocarp microsomal fraction binds fewer substrates than does the rat liver enzyme system. Type I binding spectra are given by fatty acids (C7-C14), aryl hydrocarbons (C7-C12), p-chloro-N methylaniline and N,N-dimethylaniline. Type II binding is seen with inhibitors of mammalian cytochrome P-450 such as metyrapone, and with the imidazole antifungal agents such as clotrimazole. 3. These binding spectra provide a rapid method for identifying possible substrates and inhibitors of avocado cytochrome P-450, and also provide information concerning the nature of the active site of avocado cytochrome P-450. 4. Avocado cytochrome P-450 catalysed the N-demethylation of N,N-dimethylaniline (17.1 nmol/min per nmol P-450) and p-chloro-N-methylaniline (13.1 nmol/min per nmol P-450), and the hydroxylation of lauric (dodecanoic) acid (1.1 nmol/min per nmol P-450). PMID- 2238706 TI - Quaternary N-glucuronides of 10-hydroxylated amitriptyline metabolites in human urine. AB - 1. Conjugated metabolites were isolated from the urine of patients receiving amitriptyline treatment using a combination of solid-phase extraction, h.p.l.c. and t.l.c. 2. By n.m.r. and mass spectrometry, N-glucuronides of E- and Z-10 hydroxyamitriptyline and of trans-10,11-dihydroxyamitriptyline were identified in addition to the previously described O-glucuronides of E- and Z-10 hydroxyamitriptyline and -nortriptyline and amitriptyline-N-glucuronide. 3. The quaternary ammonium glucuronides proved to be resistant to acid hydrolysis, but could be cleaved enzymatically. 4. In urine samples from three patients, 35-60% of conjugated 10-hydroxyamitriptyline was found in the form of N-glucuronides. 5. A volunteer given an i.v. infusion of amitriptyline-N-glucuronide excreted E- and Z-10-hydroxyamitriptyline-N-glucuronide; following ingestion of E-10 hydroxyamitriptyline its N-glucuronide could be measured in urine. PMID- 2238707 TI - Analogues of N-hydroxy-4-acetylaminobiphenyl as substrates and inactivators of hamster hepatic acetyltransferases. AB - 1. A series of analogues of N-hydroxy-4-acetylaminobiphenyl (1, N-OH-AAB) has been synthesized and evaluated in vitro as substrates and inactivators of hamster hepatic N,N-acetyltransferase (N,N-AT) activity. The analogues of 1 are N arylhydroxamic acids in which an atom or small functional group has been incorporated between the phenyl rings of 1. 2. The structural and molecular properties of the atoms between the two phenyl rings had little influence on the ability of the compounds to serve as acetyl donors in the N-arylhydroxamic acid dependent transacetylation of 4-aminoazobenzene (AAB) catalysed by N,N-AT. An exception was the SO2 analogue (6) which was inactive. 3. All of the compounds except 6 were mechanism-based inactivators (suicide inhibitors) of hamster hepatic N,N-AT. The inhibition of N,N-AT by the hydroxamic acids was irreversible. The properties of the atom or functional group between the phenyl rings had a substantial influence on the relative effectiveness of the compounds as inactivators of N,N-AT. trans-N-Hydroxy-4-acetylaminostilbene (N-OH-AAS, 7) was the most potent and effective mechanism-based inactivator among the compounds studied. The ketone analogue (2) was the least effective among the compounds that exhibited inactivating activity. 4. The presence of the nucleophile cysteine in the incubation mixtures reduced the extent of inactivation of N,N-AT by 1 and by the ether (4) analogue but had little effect on the inactivation caused by 7. The inactivation of N,N-AT by N-OH-AAS (7) does not appear to involve electrophiles that are released from the active site and subsequently become covalently bound to the enzyme. PMID- 2238708 TI - Oxidative injury mediated by the hepatic cytochrome P-450 system in conjunction with cellular iron. Effects on the pathway of haem biosynthesis. AB - 1. Some polyhalogenated aromatic chemicals such as 2,3,7,8-tetrachloro-p-dioxin, brominated and chlorinated biphenyls, and hexachlorobenzene cause in humans, animals and hepatocyte systems a partial block in haem biosynthesis leading to accumulation and excretion of uroporphyrin, the oxidation product of the unstable biosynthetic intermediate uroporphyrinogen. 2. The involvement of reactive toxic metabolites of the halogenated chemicals has previously been suggested. The evidence presented in this paper supports a different mechanism involving chronic induction of the microsomal cytochrome P-450 system, mobilization of hepatocellular iron and associated oxidative stress. Besides oxidation of uroporphyrinogen to uroporphyrin, an inhibitor of uroporphyrinogen decarboxylase may also be formed. 3. Studies with iron-loaded mice and chicken embryo hepatocytes show that under appropriate conditions iron alone, or chemicals such as beta-naphthoflavone which induce the same cytochromes P-450 isozymes as do the chlorinated aromatics, will cause a similar uroporphyria. These findings provide an experimental model for the human disease porphyria cutanea tarda, sometimes occurring in patients with liver damage. 4. Experiments with rats and iron-loaded mice indicate that there may also be an association between the induction of uroporphyria and the development of liver tumours after administration of polyhalogenated aromatic chemicals. PMID- 2238709 TI - Effects of glutathione depletion, chelation and diuresis on iron nitrilotriacetate-induced lipid peroxidation in rats and mice. AB - 1. Rats and mice dosed with iron nitrilotriacetate (FeNTA) i.p. (2-12 mg Fe/kg) showed evidence of lipid peroxidation as indicated by increased exhalation of ethane and increased malondialdehyde formation in liver and kidney. 2. Buthionine sulphoximine (BSO) administered i.p. to rats and mice decreased the total glutathione (GSH) content of liver and kidney. When the rodents were pretreated i.p. with BSO prior to injection of FeNTA the increases in ethane exhalation, and in liver and kidney malondialdehyde production, were greater than with FeNTA alone, and the total GSH of liver and kidney were decreased. 3. Diuresis produced by i.p. administration of furosemide to mice substantially decreased the ethane exhalation resulting from FeNTA administration, had a lowering effect on kidney MDA, but had no significant effect on liver MDA production. 4. Similarly, desferrioxamine beta-mesylate administered i.p. to mice markedly decreased the ethane exhalation and kidney MDA production resulting from FeNTA administration. PMID- 2238710 TI - A review of recent studies on the metabolism of exogenous and endogenous malondialdehyde. AB - 1. The generation of malondialdehyde (MDA), a mutagenic product of the oxidative decomposition of highly unsaturated fatty acids in vivo, is increased by exposure to certain environmental oxidants and xenobiotics. 2. This increase is reflected in enhanced excretion of several MDA derivatives in the urine. The main urinary metabolites of MDA have been identified as N-epsilon-(2-propenal)lysine and its N alpha-acetyl ester. 3. Two minor metabolites have been identified as enaminals formed by reactions with the phospholipid bases serine and ethanolamine. A further MDA metabolite has been identified as a cyclized adduct with guanine. 4. These urinary compounds reflect the turnover of proteins, phospholipids and nucleic acids that have been modified by reactions with MDA in vivo. Monitoring of the urinary adduct with guanine may provide a practicable method of assessing the effect of xenobiotics and other factors on in vivo lipid peroxidation. 5. The proportion of total MDA in the diet, blood, urine and solid tissues that exists in the free state appears to be negligible. 6. Chronic oral administration of the enol Na salt of MDA to animals produced no significant pathology except for dose dependent lesions of hepatic nuclei. Nuclear abnormalities in cultured rat skin fibroblasts were seen at intracellular concentrations as low as 10(-7) M. PMID- 2238711 TI - Reactive oxygen and glomerular dysfunction. AB - 1. The function of the kidney glomerulus, and the formation of reactive oxygen species in the glomerulus, is reviewed. 2. Experimental models of glomerular injury, resulting from immunological and non-immune reactions, are known to give rise to morphological and functional changes of the glomerulus, resulting in proteinuria. 3. From the use of oxygen radical scavengers and inhibitors, glomerular injuries have been shown to be associated with the production of hydrogen peroxide, hydroxyl radical, and superoxide anion radical. PMID- 2238712 TI - Molecular mechanisms for bromotrichloromethane cytotoxicity in isolated rat hepatocytes. AB - 1. Bromotrichloromethane added to isolated rat hepatocytes resulted in increased cell death as determined by trypan blue uptake. Toxicity increased in a concentration-dependent fashion between 2.0-5.0 M bromotrichloromethane. 2. Lipid peroxidation (malondialdehyde) increased in a time-dependent fashion but in contrast to toxicity reached a maximum level at 2.0 mM bromotrichloromethane. 3. Hypoxia increased the toxicity of bromotrichloromethane three-fold but only decreased the amount of lipid peroxidation to a small degree. 4. In spite of this poor correlation between toxicity and lipid peroxidation, the antioxidant butylated hydroxyanisole and the iron chelator desferal protected the cells from toxicity under both aerobic and hypoxic conditions and prevented lipid peroxidation. 5. During treatment with bromotrichloromethane, cellular glutathione levels slowly decreased and oxidized glutathione appeared in the media. The addition of cystine to the incubation media prevented the formation of extracellular oxidized glutathione, indicating that cellular glutathione had leaked from the cell during treatment and was oxidized in the incubation media. Although this suggested that glutathione does not play a protective role against bromotrichloromethane toxicity, diethyl maleate-pretreatment of the cells to decrease glutathione levels markedly increased bromotrichloromethane toxicity. 6. The addition of ascorbic acid to the incubation media increased bromotrichloromethane toxicity. This was attributed to the reductive activation of bromotrichloromethane in an iron and oxygen-dependent reaction. 7. It was concluded that peroxidation of essential phospholipids contributes to bromotrichloromethane-induced hepatocyte cytotoxicity. PMID- 2238713 TI - Toxicity of nitrobenzene compounds towards isolated hepatocytes: dependence on reduction potential. AB - 1. The cytotoxicity of p-substituted nitrobenzenes towards isolated hepatocytes under aerobic or hypoxic conditions has been determined. The nitrobenzene concentration required to cause 50% cytoxicity in 2 h was a function of the one electron reduction potential of the nitrobenzene, with the more cytotoxic compounds having the strongest electron-withdrawing substituents. 2. The effectiveness of the nitrobenzenes at causing cytotoxicity under aerobic but not hypoxic conditions was markedly increased if hepatocyte catalase was inhibited with azide. 3. Nitrobenzenes at cytotoxic concentrations induced cyanide resistant respiration in isolated hepatocytes. Their effectiveness correlated with their cytotoxicity. 4. The rate of oxygen activation of these nitrobenzenes by ascorbate was also a function of the one-electron reduction potential. The nitro compounds with the strongest electron-withdrawing substituents were the most rapidly reduced. 5. Most nitrobenzenes were more cytotoxic under aerobic than hypoxic conditions. Ascorbate enhanced hypoxic, but not aerobic, cytotoxicity. 6. It was concluded that the cytotoxicity of different nitrobenzenes is related to their ease of reduction to nitro radical anions and nitrosobenzenes. Aerobic cytotoxicity is probably initiated by redox cycling and oxygen activation by the nitro radical anions whereas hypoxic cytotoxicity is probably initiated by the alkylation of macromolecules by nitrosobenzene metabolites. PMID- 2238714 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced decrease in the fluidity of rat liver membranes. AB - 1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCCD)-induced lipid peroxidation has previously been demonstrated by assessing the hepatic content of thiobarbituric acid reactive substances (TBARS) as well as the NADPH-dependent microsomal formation of TBARS as well as the NADPH-dependent microsomal formation of TBARS using malondialdehyde as the standard. 2. Changes in membrane fluidity as a result of lipid peroxidation may occur. Therefore the dose- and time-dependent effects of TCDD on lipid peroxidation in mitochondrial, microsomal, and plasma membranes, and changes in membrane fluidity in these subcellular fractions, were examined. Animals were treated with either 50 or 100 micrograms TCDD/kg orally, and killed 3, 6, or 9 days post-treatment. 3. Time-dependent increases occurred in TBARS content and formation following TCDD administration for all three membranes. Similar results were observed after 50 and 100 micrograms TCDD/kg. 4. Following TCDD administration, fluorescence polarization measurements as determined by the fluorescence polarization (r) and anisotropy parameter (a.p.) values demonstrated significant decreases in membrane fluidity in all membrane fractions, indicative of membrane structural alterations. 5. Excellent inverse correlations between lipid peroxidation and membrane fluidity were observed. Thus, decreased membrane fluidity and increased membrane damage may contribute to the toxic manifestations of TCDD as a consequence of an oxidative stress. PMID- 2238715 TI - Orthopaedic manifestations of sickle-cell disease. AB - Sickle-cell disease is a well-recognized clinical entity. The pathophysiology of this hemoglobinopathy has been described in detail by numerous investigators since the first case report appeared in 1910. Orthopaedic manifestations of sickle-cell disease account for much of the morbidity associated with this disorder, including pain, osteonecrosis, arthritis, and sepsis. Effective management of these bone and joint sequelae reflect accurate diagnosis, understanding of this disorder's pathophysiology, and knowledge of available medical and surgical treatment alternatives. In this review, the authors summarize the major orthopaedic manifestations of sickle-cell disease with special emphasis placed upon osteonecrosis and osteomyelitis, since these conditions are the most disabling and serious complications in patients with sickle-cell disease. PMID- 2238717 TI - [Therapy of peptic ulcer]. PMID- 2238716 TI - Tourette's disorder and associated complex behaviors: a case report. AB - A case of a man with Tourette's disorder associated with obsessive-compulsive disorder, multiple sexual paraphilias, and aggressive behavior is described. Treatment with haloperidol led to improvement in the characteristic tics of Tourette's disorder as well as to improvement in these three complex-associated behaviors. After haloperidol was discontinued, an exacerbation of tics and the associated behaviors occurred. PMID- 2238719 TI - [Survey: What should be done in epigastric pain?]. PMID- 2238718 TI - [Occupational medicine aspects in gastroenterologic diseases]. PMID- 2238720 TI - [Dietary treatment of hyper- and dyslipoproteinemias]. PMID- 2238721 TI - [Age-dependent development of eosinophilia in nasal secretions in children with chronic non-specific respiratory diseases]. PMID- 2238722 TI - [The value of retrograde pneumoileography in evaluating enterocolic anastomoses]. PMID- 2238724 TI - [Therapeutic possibilities in high degree penis deviation in adulthood]. PMID- 2238723 TI - [Ulcerating esophagitis caused by doxycycline]. PMID- 2238725 TI - [Repeated self-mutilation caused by ingestion of a coumarin derivative]. PMID- 2238726 TI - ["When the hour strikes"--thoughts on dying in the aged]. PMID- 2238727 TI - [Student experiences in the "clinical rotation in social service"]. PMID- 2238728 TI - [German-Polish edicts of the 18th century as a source in the history of medicine]. PMID- 2238729 TI - [Cardiodynamic determinants of heart perception]. AB - Subjective perception of one's heartbeat is augmented by psychological factors (stress, fear) as well as by physiological influences (e.g., physical work). It is still unclear on which cardiac or circulatory parameters the "signal" for cardiac perception is based. In this study, the relation between cardiac performance and the ability to perceive one's heartbeat was investigated. Sixteen healthy subjects (8 female, 8 male, aged from 21 to 31 years) participated. Cardiac activity was varied by a combination of passive tilt and physical work on a bicycle ergometer. Subjects had to perform physical work (0, 25, 50, 75, 100 W) on the bicycle at seven different angles (90 degrees, 75 degrees, 60 degrees, 45 degrees, 30 degrees, 15 degrees, 0 degrees). A cardiac perception test was carried out after each load. The following cardiodynamic parameters were measured: stroke volume, contractility, and heart rate. The mean correlation coefficient between cardioceptive performance and cardiodynamic parameters was .62 for stroke volume, .45 for contractility, and .12 for heart rate. Obviously, a remarkable relation exists between the mass and--to a lesser degree--the velocity of ejected blood and cardiac perception. From this we infer, tentatively, that the subjectively perceivable heartbeat stimulus is generated by mechanical events that occur close to the left ventricle. PMID- 2238730 TI - [An experiment on the theory of visual motion perception]. AB - Two classes of theories of motion perception were studied: correlation and gradient models (in the sense of D. Marr). Random-dot kinematograms with a shifted square were presented to subjects, and the 80% threshold for detection of correct direction of movement was determined. Correlation models predict scale invariance, that is, a constant shift measured in units of texture elements of the translated pattern in spite of a geometric magnification. This was refuted for all subjects. The increase of the recognizable translation with the area of the translated form was verified except for the patterns with the largest texture elements (8 minutes of arc). This prediction, however, is not very specific for competing theories. Gradient models are not yet fully specified, and they contain some free parameters. They cannot be tested strictly, but there exist reasonable numerical parameter values by which our data can be satisfactorily explained. PMID- 2238731 TI - [The course of mimetic reactions during presentation of pictures with positive, neutral and negative value]. AB - The EMG reactions of m. corrugator supercilii, m. frontalis lateralis, m. zygomaticus major and m. depressor anguli oris in 21 male subjects were recorded during a 5-second presentation of pictures with positive, negative, and neutral valence. Compared with the m. zygomaticus activity during the presentation of pictures with neutral and negative valence, the activity in the m. zygomaticus area was prolonged during the presentation of pictures with positive valence. The response curve of m. zygomaticus activity during presentation of pictures with positive valence showed a slight negative quadratic trend with maximum activity at 3 seconds after stimulus presentation. Compared with the activity during the presentation of pictures with positive and neutral valence, the activity in the m. corrugator area was prolonged during the presentation of pictures with negative valence. The response curve of m. corrugator activity during presentation of pictures with negative valence showed a tendency toward a negative quadratic trend with maximum activity at 3 seconds after stimulus presentation. During the presentation of all pictures the activity in the m. frontalis area yielded a strong negative linear trend with maximum activity in the first second after stimulus presentation. This might be attributed to the phenomenon of "habituation." Interestingly, after the presentation of pictures with negative valence, the response curve of m. frontalis activity showed a diminished linear trend compared with the linear trends after presentation of pictures with positive and neutral valence. This might be attributed to the phenomenon of "defensive reaction." PMID- 2238732 TI - [Sex differences in memory performance for odors, tone sequences and colors]. AB - Sense of olfaction would seem to be of little importance for human behavior. However, a closer look at this from the psychological point of view reveals many interesting aspects, such as sex differences in olfactory perception, that are of interest to differential psychology. The present study deals with sex differences in the memory for odors; we assume that women will do better here than men while other memory tasks involving acoustical and optical stimuli will show no such differences. Sixty women and 40 men were examined. On the first day, they had to retain 10 odors, 10 random-generated tone-sequences, and 10 colors. On the second day, 20 such stimuli for each memory task were presented, and the subjects had to remember and to tell which were known and which of them were unknown stimuli to them. A significant advantage in the olfaction memory task was found for women, while acoustical and optical memory scores showed no such differences. This expected finding is discussed in two ways. First, the female advantage might result from phylogenetic sources. Second, it might arise because women in general more often than men seem to deal with olfactory cues, so that they might simply have more experience and therefore the greater chance to score higher in an odor memory task. PMID- 2238733 TI - [The number of active sweat glands (PSI, palmar sweat index) in stress caused by blood donation]. AB - The number of active sweat glands (PSI), heart rate, systolic (SBP) and diastolic blood pressure (DBP) were assessed every 2 minutes in 109 male blood donors. Three measurements were taken at the beginning (adaptation phase), three later but before blood donation (baseline), one during the venous puncture (phase 3), three thereafter but still during donation (phase 4), and four after removal of the cannula (phase 5). Analysis of variance yielded significant differences between phases; PSI and SBP behaved similarly, decreasing from adaptation to baseline, rising during puncture, and decreasing again thereafter. Mean within subject correlations between variables were significantly above 0. Between subjects correlations were significantly negative for PSI and DBP. This is best explained by the influence of age on both variables. Correlations of PSI values as determined by three raters had a mean of 0.90. The study shows that the PSI is a very sensitive indicator of stress that is easily accessible also in field studies. PMID- 2238734 TI - [Trends in medical microbiology--gene probes in medical microbiology]. AB - At first the principle of nucleic acid hybridisation, some important technics used heretofore, and methods to label nucleic acids are described. The advantages and disadvantages regarding to the application to microbiological diagnostics are discussed. The advantage, before all, is the high specificity of the test which allows to detect the presence and the properties of genes which are not expressed. The methods known up to now can only be applied if the probe is labelled radioactively, since under these conditions the sensitivity is high enough to identify bacteria contained in clinical isolates without prior cultivation. The comparable complex methods are restricted, presently, to special mostly epidemiological problems. To improve these technics regarding increased sensitivity, to the use of non-radioactively labelled probes, to higher speed, and to the automation of the test internationally much work is carried out with great intensity. The solution of these problems will create conditions for a wide application of DNA probes in the general microbiological laboratory. PMID- 2238735 TI - [Special events and averages in handling of poisons in the years 1980 to 1988 (statistical overview)]. AB - Authors statistically analysed the "special events" in handling poisons registered by the Ministry of Public Health of GDR in the years 1980 to 1988. Emphasis was the evaluation of causes. Perceptible tendencies of development in this matter were presented. PMID- 2238736 TI - [NO2 exposure and hydroxyproline excretion]. AB - The determination of hydroxyproline (HOP) and of the HOP-creatinine ratio in urine, respectively, is according to the literature probably a parameter of NO2 caused collagen damage of the respiratory organs and therefore a parameter which could be used for biological monitoring of indoor exposures. Own studies on children from gas or electrical house keeping presented no significant differences. Various interpretations are discussed, further investigations seem to be indicated. PMID- 2238738 TI - On the content of arsenic, lead, copper, zinc, tin and iron in bottled fruit, strained fruit pulp and bottled jam produced in Poland. AB - One hundred and fifty-three samples of bottled fruit, strained fruit pulps and jams contained in glass jars were analysed for heavy metals. All arsenic concentrations were less than the limit of detection of 0.04 mg/kg as were all tin concentrations for which the limit of detection was 8 mg/kg. The concentrations of the lead were all below 0.2 mg/kg for bottled fruit and 0.3 mg/kg for stained pulps and jams. In bottled fruit 98% of samples contained less than 3 mg/kg of copper, 98% less than 5 mg/kg of zinc and 97% less than 10 mg/kg of iron. In strained pulps all samples contained less than 2 mg/kg of copper and less than 5 mg/kg of zinc, 41% of samples contained less than 20 mg/kg of iron. In jams all samples contained less than 2 mg/kg of copper and less than 5 mg/kg of zinc, 96% samples contained less than 20 mg/kg of iron. PMID- 2238737 TI - [Study of heavy metal immission with dust sedimentation in various regions of the GDR. Results of a nationwide study of 144 measuring points (1983-1988)]. AB - Dust sediment samples had been taken continuously from 1983 to 1988 in the environment of trace element emitting industrial plants, in industrial centers, in urban regions without specific deposits, and in background regions of the GDR. After wet digestion the concentrations of 17 elements (Ca, Fe, Al, Mg, Na, P, Zn, Mn, Ti, Ba, Pb, Sr, Cu, Cr, Cd, V, Be) have been determined by atomic emission spectrometry (ICP) and calculated as element fallout (mg/m2 x 30 d). More than 60,000 data underlie statistical analysis. Measuring points with geometrical averaged immissions of significant elements (Zn, Cu, Pb, Cd, Be, Cr, V) above the 84-percentile of all measuring points are listed separately. Very heavy sources of all analysed elements are steel plants more than nonferrous metal plants. The northern territories of the GDR are comparatively slightly impacted. PMID- 2238739 TI - [Properties and biological effect of dust of various artificial mineral fibers]. AB - Developments and use of man-made mineral fibres are important for the progress in some technical fields. In the last years the number of man-made mineral fibres increased extraordinarily. For the medical evaluation it is necessary to determine the physico-chemical characteristics of the man-made mineral fibre dust and its biological effects in animal experiments. The results of the investigations are described. PMID- 2238740 TI - [Epidemiological aspects of spinal diseases in the GDR in 1979 to 1988]. AB - The socio-economic impact of disorders of the spine and the back has obtained an increasing importance in all industrial countries. Considering indicators of public health and national economy, namely temporary sickness incapacity for work, invalidity (insured persons in the GDR), utilization of hospital services (total population of the GDR), of rheumatological dispensaries as well as of the general practitioner, frequencies have been studied and trends pursued by means of serial analyses in a 10-year period. Diseases of the spine and the back within diagnostic class XIII/ICD, 9th revision, 1975 (diseases of the musculoskeletal system and connective tissue) have caused--nearly 2/3 of all cases of sickness incapacity for work--1/3 of the incidence of disability pensions--about 1/3 of the utilization of hospital services--about 1/5 of the utilization of rheumatological dispensaries--more than 50% of all cases consulting the general practitioner. As to the indicators sickness incapacity for work, incidence of disability pensions and discharges from the hospital, the serial analyses of the period from 1979 to 1988 have shown that the diseases of the spine and the back have the highest increase within the group of class XIII. PMID- 2238741 TI - [Progression of noise-induced hearing loss in exposed agricultural workers--ADP projects "LADA" and "LEQ"]. AB - For years now, the survey of noise deafness as an officially recognized occupational disease has shown agriculture, forestry and the foodstuff industry to be a problem field. This is particularly true of operators of self-propelled machines and tractors. As far as the causes are concerned, it is more or less only presumptions that have been voiced hitherto, since the real noise-exposure data (particularly long-term recordings) has been lacking. For the long-term storage of exposure and audiometry data two reusable computerized projects have been worked out. Employing them, researchers can obtain noise-deafness progression data on an individual basis, based on the individual's noise-exposure data. The preliminary assessment of the data of nearly 1000 workers shows that both the noise exposure and the extent of the hearing loss vary greatly between individuals. This adds the necessity of an individual-based recording of the noise-exposure data. PMID- 2238742 TI - [Studies on the combined effects of shift work and noise on permanent hearing loss]. AB - Combined exposure to shiftwork and noise was investigated with respect to its aural damaging effect. The investigations were carried out on 347 male and female noise-exposed textile workers working in single-shift and three-shift systems. The average hearing loss for the PTS at 3 kHz, 4 kHz, the total hearing loss at 0.5, 1, 2, 4, 6, 8 kHz and percentage of hearing loss according to Fowler/Sabine served as indicators. To fulfil this task an epidemiological cross-sectional study was performed. The results of the present study show lower average hearing loss values in the case of three-shift workers as compared with single-shift workers. PMID- 2238743 TI - [Occupational hygiene examinations of carpenters' activities in a Berliner building plant]. AB - The state of health of carpenters is examined in relation to the field associated with their occupations. In this connection the results of occupational medicine concerning examinations for suitability and of observation, the recognized occupational diseases and notifiable industrial accidents are analysed and compared with those of production workers in the building and construction industry. The reasons for higher rates of findings and occupational diseases by carpenters are discussed and conclusions for occupational medical care are drawn. PMID- 2238744 TI - [Combined effects of pharmacological activation of the CNS and the complexity of mental tasks on the function of the cardiovascular and the vegetative nervous system and the work performance of operators]. AB - Effect of central nervous activation and of mental workload depends on the regime of operator work. To evaluate the level of activation by means of a set of psychophysiological indices and performance data is recommended a regime of fixed working speed. PMID- 2238745 TI - [Continuous measurement of muscular stimulation conduction velocity using surface electrodes--methodical prerequisites and results]. AB - During long-lasting static muscular work fatigue is accompanied by a shift of the mean power frequency (MPF) of EMG power density spectra to lower frequencies. It is mostly accepted that changes in MPF with the onset of fatigue are mainly related to a decrease in muscle fibre conduction velocity (CV) caused by changes of the electrical properties of the fibre membrane. A method was developed for the continuous measurement of CV from surface electromyograms (EMG). The CV is estimated from the time delay between EMG signals recorded by a multielectrode configuration placed over the muscle between tendon and endplate region. Further processing and artifact rejection was realized in a hardware solution. Results obtained by this methods from investigations of muscle fatigue and temperature related changes in MPF and CV are presented. PMID- 2238746 TI - [The effect of moderate oxygen deficiency on volume regulation in man]. AB - In acute hypoxia or at pharmacological stimulation of the peripheral arterial chemoreceptors by almitrine, a transient natriuresis and diuresis occurs. Depending on the starting level, e.g. on the state of water diuresis or the osmotic diuresis, the renal excretion responded differently in our examinations. In water diuresis the water excretion increased isolatedly. In the opposite to the osmotic diuresis, the natriuresis did not increase. This response might be based on the proximal inhibition of the sodium and water reabsorption at following augmented distal sodium reabsorption and suppressed distal water reabsorption. In this way the organism is able to respond with increased water excretion at sodium excretion kept constant or with diuresis and natriuresis when arterial chemoreceptors are stimulated. PMID- 2238747 TI - [Asymptomatic myocardial ischemia]. AB - Silent (asymptomatic) myocardial ischemia (SMI) is defined as a transient alteration in myocardial perfusion in the absence of chest pain or the usual anginal equivalents. Patients may be classified as having one of the three types of SMI: type A--totally asymptomatic patients with no history of angina or myocardial infarction; type B--asymptomatic patients with previous myocardial infarction; type C--patients with angina and asymptomatic ischemic episodes. SMI has been found in 2.5% of all healthy males aged 40-59 and in 20% of all postinfarction patients. In type C-patients, 80% has been found to have asymptomatic ischemic episodes in addition to typical angina pectoris. The frequency of SMI may be up to three or four times that of anginal attacks. SMI patients have generally reduced sensitivity to pain an differences in severity an duration of ischemic episodes. Diagnosis is based on screening by means of exercise testing in patients working in specific professions (like pilots, busdrivers etc.), in postinfarction patients and in patients after unstable angina pectoris and after coronary bypass surgery or coronary angioplasty. Prognosis is the same as in asymptomatic ischemia. SMI is an indicator of instability in certain groups of patients (post infarction, after unstable angina pectoris). SMI persisting after medical therapy of unstable angina is associated with adverse short-term-prognosis, therefore coronary surgery or angioplasty is indicated. PMID- 2238749 TI - [Role of the occupational health service in the control of hypertension]. AB - By a representative random sample in an order of magnitude of 5,150 employees the determination of the degree of knowledge of the hypertensives in the factory health service of metal mines showed nearly 100%. In the dispensary of the factory medical officer 64.2% were registered. 36.6% of the hypertensives were stabilised to blood pressure values below 160/95 mm Hg. Forms of therapy, cardiovascular risk factors associated with high blood pressure and effects of the working environment were investigated by means of factor and discriminance analysis with regard to the influence on the quality of the stabilisation of high blood pressure. The compliance resulted as essential limiting factor in the treatment of hypertension. 71% of the hypertensives reported a regular intake of medicaments, in which case 51% admitted to interrupt it without consulting the physician in charge when the constitution is disturbed. 4 features were determined as essential factors which have influence on the compliance: the opinion concerning the duration of the treatment of hypertension, the attitude to the intake of medicaments, the frequency of the intake of the tablets and the observation of the terms of blood pressure control. The investigation of the physician's compliance resulted, apart from an overestimation of the patient's compliance, in distinct deviations from the recommendations for diagnosis and therapy given. The compliance of nurses showed deficiencies in the standardized measurement of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238748 TI - [Does the calcium antagonist verapamil modify calcium metabolism?]. AB - In 11 healthy volunteers the effects of oral verapamil administration (4 X 80 mg/d) on plasma or serum concentrations of ionized, pH-corrected ionized and total calcium, on intact and midregional parathyroid hormone and on 24 h urinary excretion of calcium were investigated at rest. In addition the concentrations of ionized, pH-corrected ionized and total serum calcium were analyzed under bicycle exercise. Verapamil resulted in an increase of total serum calcium (p less than 0.02) and a fall in midregional parathyroid hormone concentrations (p less than 0.02) at rest. There was also found a statistically significant elevation of both ionized (p less than 0.05) and pH-corrected ionized (p less than 0.05) plasma calcium, and a slight increase in the total calcium under exercise (p less than 0.1). Before verapamil a significant negative correlation between total calcium and midregional parathyroid hormone was evident (r = -0.618; p less than 0.05), which however could not be clearly discerned after verapamil. PMID- 2238750 TI - [Heart wall rupture as a grave complication of acute myocardial infarct]. AB - The rupture of the heart wall is a severe complication of the acute myocardial infarction. We found it in 3.5% of the deceased patients with an acute myocardial infarction. The average age of these patients was 71 years. 75% of the patients died during the first five days after the event of the myocardial infarction. Apart from elderly patients with myocardial infarction such ones with a transmural myocardial infarction in the region of the left ventricle, an enlargement of the heart and signs of an insufficiency of the left heart, with a hypertension and diabetes mellitus seemed to be endangered. These patients need the most exact control and observation and in case of suspicion (symptomatology of angina pectoris which is continuing to exist) of a developing rupture of the heart wall and aimed diagnostics (echocardiography) and therapy must be begun immediately. PMID- 2238751 TI - [The frequency of demonstration of Campylobacter pylori]. AB - In 376 patients who underwent gastroscopy the presence of Campylobacter pylori by microscopy, bacterial culture and urea test was studied. Additionally, the histological examination of the antral mucosa was performed. The organisms were detected in 47.9% of the biopsy specimens (37.2% in normal endoscopic findings and 70% in duodenal ulcers). Dependence on sex was not found and also no significant difference of Campylobacter pylori detection in patients younger than 45 years compared with those who are older. However there was a strong correlation between the presence of Campylobacter pylori and the histological results (p less than 0.05). In comparison with international literature we found a distinctly lower percentage of positive Campylobacter pylori rate in patients with peptic ulcer; the association between the presence of Campylobacter pylori and the degree of gastritis was confirmed. PMID- 2238753 TI - [Antagonizing the effect of midazolam by flumazenil in gastroscopy: results of a randomized double blind study]. AB - The action and side effects of the benzodiazepine antagonist Flumazenil were evaluated and compared with placebo in a double blind parallel group randomized trial involving 40 patients having upper gastrointestinal endoscopy under Midazolam premedication. Flumazenil reversed the hypnotic effect of midazolam within a few minutes. The patients were alert, cooperative, oriented and had recall of events after endoscopy. The effects were better than placebo concerning alertness for up to 30 minutes after administration whereas drowsiness remained almost stable after placebo. Time to reach full alertness was shorter after Flumazenil compared with placebo (42 vs 62 minutes). There were no significant side effects. Flumazenil allows effective reversal of midazolam premedication after upper gastrointestinal endoscopy. PMID- 2238754 TI - Elimination of Helicobacter pylori under treatment with omeprazole. AB - Biopsies from the stomachs (antrum and corpus) of 201 patients with peptic ulcers or reflux oesophagitis were retrospectively investigated for the effect of treatment with omeprazole on the elimination of Helicobacter pylori (HP) and on gastritis. Of 64 patients without gastritis two (3.1%) developed gastritis during treatment. Among 134 patients with HP gastritis undergoing treatment, 48 (35.8%) experienced no HP elimination, in 41 (30.6%) there was HP elimination from the antrum, but HP persistence in the corpus, while in 45 (33.6%) HP was eliminated from both antrum and corpus. HP elimination led to a reduction in the degree and activity of gastritis under omeprazole treatment. Only eight patients were examined after completion of treatment, and in three in whom HP had been eliminated, recolonization was found to have occurred. The disappearance of HP in Type A gastritis coupled with the fact that HP is highly sensitive to contamination with other bacteria--as observed in the laboratory--suggests that this now partially established elimination of HP under the strongly acid inhibiting omeprazole therapy can be traced back to a bacterial overgrowth of the gastric mucosa. PMID- 2238752 TI - [Various memorable dates from the history of smallpox vaccination]. AB - Several dates of memory from the history of the vaccination against smallpox are to be registered for the year 1990. The birthday of the vaccination propagandist Johann Adam Reimann comes round the 300th time, the initial date of relevant university instructions comes round the 200th time. Issuing from this the history of vaccination against small pox is touched on at the instance of several marking points. PMID- 2238755 TI - [Effect of pancreatin on diabetes mellitus in chronic pancreatitis]. AB - The effect of pancreatin on insulinopenic diabetes was studied in 10 patients with chronic pancreatitis and exocrine function impairment. All patients were treated for 4 days in a randomized crossover trial with either pancreatin (6 x 2 capsules, 6 x 300 mg/d) or placebo. Blood glucose levels were determined 7 times every day and night. On day 5, the patients were studied by a glucose sensor with adjustment of blood glucose to 120 mg/dl until 8.00 in the morning. A test meal was applied with 2 capsules pancreatin or placebo. Blood glucose and plasma levels of C-peptide, glucagon and pancreatic polypeptide (PP) were determined in regular intervals for 4 hours. Blood glucose levels were not significantly altered by pancreatin. As shown by M-value according to Schlichtkrull (21.6 +/- 2.9 versus 32.4 +/- 7.4), there was a tendency towards smaller oscillations of blood glucose with pancreatin treatment. C-peptide levels (basal 0.081 +/- 0.008 ng/ml; postprandial 0.119 +/- 0.013 ng/ml) were not significantly altered by the administration of pancreatin. Basal and postprandial glucagon and PP plasma levels were not influenced by pancreatin. From these results, we conclude that pancreatic enzyme supplementation does not significantly alter the requirement of insulin in patients with diabetes mellitus secondary to chronic pancreatitis. Possible disturbances of the enteroinsular axis are discussed in this paper. PMID- 2238757 TI - [Duplex sonography measurement of portal vein blood flow with healthy livers and in patients with chronic hepatitis after a fully absorbable test meal]. AB - In 36 patients with chronic viral hepatitis and 20 patients with an intact liver we determined the blood flow and blood flow velocities of the portal vein by means of duplexsonography. This was done before and after the intake of a test meal (Biosorbin MCT). According to preexisting data the cases of chronic hepatitis were subdivided into groups consisting of 14 cases having chronic persistent hepatitis, 9 cases having chronic aggressive hepatitis without tendency of cirrhotic transformation and 13 cases of chronic aggressive hepatitis with beginning cirrhotic changes. Patients with known cirrhosis of the liver or signs of portal hypertension were excluded from the study. It was not possible to assign a patient with chronic hepatitis to a definite group merely on the knowledge of his portal blood flow. Only after the intake of the test meal varying increases in blood flow velocity and volume were demonstrated. These increases were found to be smallest in the group of "chronic aggressive hepatitis with developing cirrhosis". In some individual cases this enabled us to conclude from changes of the portal blood flow whether or not a portal hypertension is developing. PMID- 2238756 TI - Comparison of GLP-1 (7-36amide) and GIP on release of somatostatin-like immunoreactivity and insulin from the isolated rat pancreas. AB - The effect of equimolar doses of GIP and GLP-1 (7-36amide) on insulin and somatostatin secretion in the isolated perfused rat pancreas was compared. At a perfusate glucose concentration of 70 mg/dl GLP-1 (7-36amide) 10(-9) and 10(-8) M and GIP 10(-9) M elicited a significant stimulation of insulin while GIP 10(-8) M and lower doses of both peptides (10(-11) and 10(-10) M) were ineffective. At elevated perfusate glucose levels of 150 mg/dl both peptides stimulated insulin release at 10(-11), 10(-10), 10(-9) and 10(-8) M but not at 10(-12) M. The insulin response at the higher glucose level was significantly greater compared to the effect of the same doses at normoglycemic conditions. Somatostatin release was stimulated significantly by GLP-1 (7-36amide) at 10(-10) and 10(-9) M at perfusate glucose level 70 mg/dl. At a glucose concentration of 150 mg/dl this effect was abolished. GIP did not alter somatostatin release at a perfusate glucose concentration of 70 mg/dl while at 150 mg/dl only the highest dose of GIP (10(-8) M) stimulated somatostatin release significantly. In conclusion, the present data demonstrate that in vitro in the rat pancreas both peptides are equally effective secretagogues of insulin release at normal and moderately elevated perfusate glucose levels. In contrast, somatostatin secretion is stimulated by GLP-1 (7-36amide) at normoglycemic conditions while only a rather high and presumably pharmacological dose of GIP is a stimulus of somatostatin secretion at moderate hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238758 TI - [Therapy and prevention of hemorrhage from esophageal varices]. AB - Management of variceal hemorrhage includes emergency treatment of bleeding esophageal varices and prophylactic treatment for the prevention of first bleeding or rebleeding. Endoscopic injection sclerotherapy appears to be the most effective therapeutic option to control acute variceal hemorrhage. When sclerotherapy fails or cannot be performed a Sengstaken-Blakemore tube can be used. Supportive treatment is provided by vasodilator or vasoconstrictor therapy. At present, operative treatment modalities such as portosystemic shunts or esophageal transection are secondary to sclerotherapy or balloon tamponade. The probability of recurrent variceal hemorrhage after a first bleeding is 70%. This necessitates preventive measures such as endoscopic sclerotherapy, beta-blockade, or surgical procedures. Meta-analysis of randomised controlled trials indicates that sclerotherapy appears to reduce the number of episodes of recurrent variceal hemorrhage better than other prophylactic treatments and to improve survival. Chronic sclerotherapy may be the procedure of first choice in patients with good liver function when elective shunt surgery is provided for those who have recurrent bleeding despite sclerotherapy. The role of beta-blockade in the prevention of recurrent bleeding remains to be clearly defined. Prevention of first esophageal bleeding by invasive treatment modalities could reasonably only be performed in patients with high bleeding risk, which, however, cannot be defined accurately at present. The use of beta-blockers in the prevention of first variceal hemorrhage should be restricted to clinical trials. PMID- 2238759 TI - [Prevention of stress ulcer hemorrhage: a risk-benefit analysis]. AB - The potential benefits and risks of prophylactic treatment for stress ulcer haemorrhage remain controversial. Analysis of previous studies indicates that 1. the incidence of haemorrhage and the mortality from haemorrhage have declined over the last two decades even in the absence of prophylactic treatment; 2. all drugs used for prophylaxis reduce the incidence of haemorrhage, and all drugs are comparably effective. 3. There is, however, no evidence that prophylactic drug therapy reduces the mortality or that the drugs used for prophylaxis differ in their effect on mortality. 4. A higher rate of pneumonia is seen only with antacid treatment. PMID- 2238760 TI - [Video-endoscopy and sonography--future developments]. AB - Video Endoscopy and Video Sonography are new developments in the field of endoscopy. They will start a structural change of the common endoscopy unit. This article shall give an overview about new development ways and their consequences for the next years in the field of Video Endoscopy. PMID- 2238761 TI - [Gastritis: immunohistochemical detection of specific and nonspecific immune response to Helicobacter pylori]. AB - Granulocyte infiltration was studied in 88 biopsies of antrum mucosa from patients with B-gastritis. Evidence of IgA-, IgG- and IgM-antibodies as well as of lysozyme in the mucosa was demonstrated by immunohistochemical methods. Helicobacter pylori (Hp) is coated by antibodies and a significant correlation between extent of opsonisation and number of plasma cells in the connective tissue of the lamina propria could be stated. Thus, the infiltration of plasma cells is a specific immune response against Hp. In the depths of gastric pits the antibody-coating of bacteria is faint. Instead, lysozyme and lactoferrin are produced there. By means of a Cross-sectional study a model is developed which characterizes B-gastritis as a dynamic process. Lagging behind, the inflammation follows the motile bacteria resulting in a patchy distribution of inflamed areas in the mucosa. At the peak of these local inflammation-waves the production of antibodies and lysozyme is intensified. Coating the bacteria with IgG and IgM results in complement activation liberating chemotaxin C5a. Consequently, there is a massive granulocyte infiltration leading to local reduction or eradication of Hp. PMID- 2238762 TI - The plain abdominal radiograph in the assessment of constipation. AB - To investigate the value of the plain abdominal radiograph in the assessment of constipation we prospectively studied 30 patients (20 females, 10 males, mean age 48.6 years, range 21-76 years). These patients underwent the following tests: plain abdominal radiograph in supine position, measurement of stool weight (mean of 5 days) and whole gut transit time (20 radioopaque pellets, fluoroscopy of stools). All patients completed a questionnaire regarding their defaecation characteristics (a.o. average defaecation frequency and faecal consistency). The abdominal films were coded and independently scored for the degree of faecal stasis in ascending, transverse, descending colon and rectosigmoid by four gastroenterologists. To each of these parts of the colon a score of 1 (no faeces) to 4 (loaded with faeces) was assigned. The film scores given by the four observers were significantly correlated (p less than 0.001). Significant correlations were found between the radiograph scores and frequency of defaecation, faecal consistency and stool weight. The strength of these correlations were of the same order of magnitude as those between the other subjective and objective defaecation variables. The scores for the left colon (descending colon and rectosigmoid) showed a better correlation with the other defaecation parameters than the scores for the right colon. It is concluded that in the assessment of constipation a simple plain abdominal radiograph is as reliable as measurement of faecal weight or marker transit and can thus be advocated as the first procedure. When an abdominal radiograph is used for this purpose the stasis in the descending and sigmoid colon provides most information. PMID- 2238763 TI - [Spontaneous bacterial peritonitis: studies of the incidence and clinical and laboratory chemical parameters]. AB - In a prospective study on 151 patients with cirrhosis of the liver we found 9 episodes of spontaneous bacterial peritonitis (SBP) in 8 patients (5.3% of the whole population or 18% of the ascitic patients). There was a clear difference in WBC-count, polymorphonuclear cell count, LDH and lactate in the ascitic fluid between SBP and controls. Clinical symptoms were discrete. 6 of 8 patients had an advanced form of cirrhosis belonging to Child-grade C. Half of patients died. The clinical situation of the 4 survivors improved after antibiotic treatment. Ascitic analysis of WBC and PMC-count in combination with LDH and lactate may reveal SBP as the reason of fever or clinical impairment in cirrhotics. PMID- 2238764 TI - [Effect of enalapril on heart rate, arterial blood pressure and exocrine pancreatic secretion in the alert dog]. AB - A changed exocrine pancreatic secretion could be a pathogenetic factor of an acute pancreatitis after administration of angiotensin-converting enzyme (ace) inhibitors. In six conscious dogs with gastric and duodenal Thomas fistulas we studied the effect of an intravenous (iv.) bolus injection of 10 mg enalaprilat, an intraduodenal (id.) bolus injection of 20 and 40 mg enalapril (e.), and 0.15 M NaCl (20 ml iv., resp., id.) on pancreatic bicarbonate- and protein output in response to secretin (20.5 pmol/kg bw/h and caerulein (29.6 pmol/kg bw/h). Arterial blood pressure and heart rate we also measured. The iv. and id. injection of enalapril(at) significantly increased heart rate by 28% after 10 mg of e. iv. [peak 101 +/- 11 beats/min, N = 6, X +/- SEM] and by 13 resp. 37% after 20 resp. 40 mg e. id. [peak 89 +/- 4, resp., 108 +/- 7 beats/min] as compared to control [peak 79 +/- 5 beats/min]. Systolic blood pressure was significantly decreased by 6% after 10 mg e. iv. [lowest value 121 +/- 2 mm Hg] and by 8% and 9% after 20 and 40 mg e. id., respectively, [lowest value 119 +/- 2, resp., 118 +/- 1 mm Hg] as compared to control [lowest value 129 +/- 1 mm Hg]. The applied enalapril(at) doses had no significant effect on hormonal stimulated pancreatic bicarbonate- and protein output. The results confirmed the well known effects of enalapril(at) on heart rate and on arterial blood pressure. Beyond that the results exposed that therapeutical doses of enalapril(at) had no significant effect on exocrine pancreatic secretion. Conclusion of this study is that a pathogenetic role of pancreatic exocrine secretion in the ace-inhibitors and the acute pancreatitis induced by ace-inhibitors is unlikely. PMID- 2238765 TI - Carbachol priming increases glucose- and glucagon-like peptide-1 (7-36)amide-, but not arginine-induced insulin secretion from the isolated perfused rat pancreas. AB - The priming effect of carbachol on glucose-, arginine- and glucose plus GLP-1 (7 36)amide induced insulin secretion was investigated. The isolated rat pancreas was perfused in vitro during a basal period of 10 min with Krebs-Ringer bicarbonate buffer containing 2.8 mmol/l glucose. This medium was then supplemented with carbachol (10,1.0.1 mumol/l, respectively). After an additional 10 min period at 2.8 mmol/l glucose insulin secretion was stimulated for 44 min with 10 mmol/l glucose, or glucose plus GLP-1 (7-36)amide (0.5 nmol/l), or arginine (10 mmol/l). Pretreatment with carbachol resulted in a concentration dependent sensitization of B-cells to a consecutive glucose load (10 mmol/l). Both phases of the biphasic insulin secretory response were significantly enhanced. Priming experiments followed by a subsequent combined glucose / GLP-1 (7-36)amide or arginine stimulation were performed with 10 mumol/l carbachol. Prior exposure of the pancrease to carbachol enhanced the glucose / GLP-1 (7 36)amide induced insulin release, but left the arginine stimulated secretion unaltered. Our data suggest that in the regulation of postprandial insulin release cholinergic sensitizing effects might be involved which are mediated by muscarinic receptors. PMID- 2238767 TI - [Risk factors in the etiology of Crohn disease]. AB - So far the aetiology of Crohn's disease remains unclear. Besides a genetic predisposition a causal role of environmental factors has been taken into consideration within the last time period. A number of case-control studies have consistently reported about an increased consumption of dietary sugar in patients with Crohn's disease as compared with controls. Furthermore cigarette smoking and the use of oral contraceptive drugs have been shown to increase disease risk. While the role of the former can be regarded as established the role of the latter still remains controversial. PMID- 2238766 TI - [Significance of the iron and copper content of the liver for the differential diagnosis of chronic liver diseases]. AB - Liver iron and copper concentrations were estimated in 395 patients undergoing hepatological examination. Relations to clinical, morphological and laboratory data were evaluated. Liver iron concentrations were not significantly different in chronic hepatitis of viral, toxic or immunological origin. Liver iron levels exceeding 100 mg/100 g dry liver tissue (normal range up to 300 mg/100 g) were only found in idiopathic hemochromatosis (n = 8), in a patient with prophyria cutanea tarda and in a multiple transfused patient who suffered from aplastic anemia. Liver copper content was significantly increased in primary biliary cirrhosis compared to chronic hepatitis of other origin. Apart from untreated Wilson's disease (n = 3) copper levels higher than 25 mg/100 g dry liver tissue (normal range up to 6 mg/100 g) were measured in chronic active hepatitis B (n = 2), primary biliary cirrhosis (n = 9) and in chronic hepatitis of uncertain origin (n = 3). Therefore excess accumulation of copper in the liver was typical of Wilson's disease but less diagnostic than severely elevated liver iron stores of idiopathic hemochromatosis. PMID- 2238768 TI - [Electronic data processing documentation of findings in gastrointestinal endoscopy]. PMID- 2238769 TI - [Adjuvant chemotherapy improves chances of survival in curative surgery of colon cancer, Dukes' stage C]. PMID- 2238770 TI - [Transesophageal echocardiography in the assessment of the severity of aortic valve stenosis]. AB - The aortic valve orifice area was measured in 95 patients with valvular aortic stenosis by means of transthoracic and transesophageal echocardiography. These results were compared to invasively determined measurements. The aortic-valve orifice area could be measured by transesophageal echocardiography in 87 patients (92%), and in 13 patients (14%) by the transthoracic approach. A comparison of the valve-orifice area determined by transthoracic and transesophageal echocardiography revealed a correlation coefficient of r = 0.91. There was also a good agreement when the aortic-valve orifice area determined by transesophageal echocardiography was compared to the invasive findings (r = 0.82; p less than 0.001). The morphology of the aortic valve could be better delineated with the transesophageal approach. PMID- 2238771 TI - [The effect of electromagnetically produced shock waves on calcified, stenosed aortic valves]. AB - To determine if electromagnetically generated shock-wave lithotripsy has potential application for treatment of stenotic, calcified aortic valves, 38 cusps of surgically excised human aortic valves were studied. Valves were weighed, photographed, and calcium deposition was determined by x-ray. Stiffness was determined by palpation and by measuring the pressure gradient generated in a perfusion system. Valves were exposed to shock waves at 16 or 18 kV with 200 or 400 impulses each. Twenty valves reacted to exposure to shock waves with a reduction in pressure gradient of 1.9 +/- 2 cm H2O. Calcified valve area was reduced by 3.5 +/- 1.3 mm2. Valves without changes in pressure gradient showed a reduction of 7.1 +/- 2 mm2 of calcified valve area. There was no significant difference in weight loss. Using a small focus (4 mm) there was a significant reduction in pressure gradient and calcified valve area, but not in weight; with a large focus (8 mm) reduction in calcified valve area, gradient, and weight was significant (p less than 0.05). Changes in valve stiffness were independent of weight loss and reduction in calcified valve area. In conclusion, shock-wave lithotripsy is capable of reducing stiffness of calcified aortic valves, presumably by fragmentation of tissue calcium deposits. PMID- 2238773 TI - [Eccentric coronary stenoses--definition and incidence in coronary angiograms]. AB - The frequency of "eccentric" stenoses was determined in 676 coronary angiograms, which proved to be useful to classify stenoses according to their position (central, eccentric), as well as to the form of residual lumen (round, not round). The results for 616 stenoses which could be evaluated for both position and form were: 30% (183/616) centrally located with round residual lumen; 10% (60/616) centrally located with no round residual lumen; 41% (255/616) eccentrically located with round residual lumen; 19% (115/616) eccentrically located with no round residual lumen. These results are in agreement with previous autopsy findings. The location and form of coronary stenoses may have different meanings: the prevalent round form of residual lumina (71% of all evaluated stenoses) may characterize a normal growing of stenoses, while no round forms might indicate complications such as ruptures with hemorrhage within plaques. The prevalent eccentric location of residual lumina (63% of all evaluated stenoses) may reflect a tendency to dynamic coronary tone within the respective coronary stenosis. This assumption is supported by similar frequencies of dilatative or constrictive responses in patients with coronary artery disease. Individual prognoses, however, with respect to coronary tone or coronary reactions cannot be predicted from morphology. PMID- 2238772 TI - [Perioperative preventive antibiotic treatment with fosfomycin in heart surgery: serum kinetics in extracorporeal circulation and determination of concentration in heart valve tissue]. AB - A prospective clinical study was carried out to assess the adequacy of perioperative antibiotic prophylaxis using fosfomycin in patients undergoing open heart surgery for valve diseases for the prevention of early postoperative endocarditis, as well as for serious mediastinal infections that are caused mostly by multiresistant staphylococci and Gram-negative bacteria. Perioperative pharmacokinetics and tissue penetration were determined within the harvested heart valves and subcutaneous tissue. Reliable bactericidal serum levels were established at the first measurement 10 min after the end of intravenous infusion (203.7 +/- 44.7 micrograms/ml) and were maintained during surgery for at least 120 min (124.6 +/- 58.4 micrograms/ml), even in cases of prolonged extracorporeal circulation. Cardiopulmonary bypass did not alter the serum elimination of fosfomycin in comparison with patients not undergoing extracorporeal circulation. Peak tissue concentrations were achieved in both aortic and mitral valves after 30 min, ranging between 27.1 and 76.9 micrograms/g for aortic valves and 39.6 69.4 micrograms/g for mitral valves, depending on the degree of valvular degeneration. MIC values of 16 micrograms/g were maintained in both valves for at least up to 60 min. There was no evidence of renal impairment, adverse reactions or infections during the postoperative course or thereafter for a period of 3 months. It is concluded that perioperative intravenous antibiotic prophylaxis using fosfomycin (5 g t.i.d. in adults), beginning with induction of anesthesia and continued for 48 h postoperatively, provides rapid, reliable bactericidal serum levels and valvular tissue concentrations that will inhibit most Gram positive and Gram-negative organisms that cause bacterial endocarditis and other serious infections following cardiac surgery. PMID- 2238774 TI - [Dipyridamole-thallium 201 tomography following acute myocardial infarct: significance for stratifying cardiac risk factors]. AB - For the purpose of risk stratification 80 consecutive patients (mean age 58 +/- 7) with a chest pain syndrome after documented myocardial infarction underwent tomographic vasodilation-redistribution thallium-201 perfusion imaging, using 0.56 mg/kg intravenous dipyridamole. Tomograms were analyzed for size and location of reversible and fixed perfusion defects and correlated to angiographic characteristics, left ventricular ejection fraction and wall motion, collateral status, and 1-year prognosis as measured by cardiac events within 14 +/- 3 months. No serious side effects were noted with the diagnostic use of intravenous dipyridamole. According to the perfusion pattern three subgroups of post infarction patients were identified: 1) by ischemia at a distance with redistribution in non-infarct related territories (n = 48), 2) by peri infarctional ischemia with redistribution in the territory of the "infarct artery" (n = 9), and 3) by exclusively fixed defects without redistribution (n = 23). Ischemia at a distance was associated with a larger reversible defect than peri-infarctional ischemia (p less than 0.05) and the pattern without redistribution (p less than 0.005); the fixed defect size, however, was similar in all three subgroups. In addition, the severity of coronary artery disease (Gensini score and number of diseased vessels) and the degree of collateralization was higher in presence of a redistribution pattern (p less than 0.05), although no significant differences in global and regional function were noted as a function of thallium-201 redistribution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238775 TI - [Decreasing length of stay in the hospital by coronary angiography with 5-French catheters]. AB - The use of 5-French (F) coronary angiography catheters as opposed to 7-F may reduce arterial injury at the puncture site. Therefore, a decrease in time to recuperation after coronary angiography with the Judkins technique seems possible. In 199 patients undergoing coronary angiography with 5-F catheters, management, imaging, and complications were investigated. In 18 patients the diagnosis of a valvular defect was confirmed; in 128 patients coronary artery disease (lesions greater than 70%) was found. Three patients had idiopathic dilative cardiomyopathy. Coronary lesions of less than 70% with normal left ventricular function were found in 50 patients ("normals"). After coronary angiography with 5-F catheters bedrest was recommended for 4 h, as compared to 24 h after a 7-F catheter procedure. Successful coronary artery imaging with 5-F catheters was achieved in 168 patients (84%). In 31 patients (27 coronary artery disease, 1 aortic stenosis, 3 normals) selective imaging was not achieved, and the 5-F catheter had to be replaced by a 7-F catheter. Aortic (systolic 147 +/- 24 vs 132 +/- 20 mm Hg, p = 0.002; diastolic 74 +/- 13 vs 70 +/- 11, p = 0.05) and left ventricular pressures (systolic 149 +/- 26 vs 131 +/- 20 mm Hg, p = 0.001; enddiastolic 18 +/- 8 vs 14 +/- 8 mm Hg, p = 0.035) were higher in this group, whereas no relations to age, sex, and diagnosis emerged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238776 TI - [Effect of acute short-term ischemia during PTCA on the function of the right ventricle]. AB - To determine whether a transient ischemia of the right ventricle leads to right ventricular impairment and whether RV function can also be influenced by septal ischemia caused by an occlusion of the left anterior descending coronary artery (LAD), RV function before and at the end of 60 s of ischemia during PTCA was assessed in 15 patients with single-vessel disease of either the right coronary artery (RCA, n = 10) or the LAD (n = 5). The RV-enddiastolic pressure and the pulmonary capillary wedge pressure (PCW) were recorded continuously. The RV ejection fraction was determined from ventriculograms performed before and during coronary occlusion. An increase of RVEDP from 3.7 +/- 1.2 to 8.3 +/- 1.8 mm Hg (p less than or equal to 0.001) and a decrease of the RV-ejection fraction from 52 +/- 3 to 33 +/- 8% (p less than or equal to 0.001) occurred during RCA occlusion with a predominant ischemia of the RV free wall only, and not during LAD occlusion with left ventricular and septal ischemia. The extent of the RV dysfunction was independent of an additional increase of RV afterload (PCW increase). Comparable to ischemic effects on left ventricular function, an acute right ventricular myocardial ischemia results in a severe RV contractile failure. PMID- 2238778 TI - [Complication in rotation angioplasty: removal of an intracoronary metal ring (roentgen marker) using a balloon catheter]. AB - Successful recanalization of an occluded left anterior descending coronary artery, performed by rotational angioplasty was complicated by loosening of a metallic ring (x-ray marker) from the rotational angioplasty system, with embolization into the circumflex artery. The metallic ring was extracted successfully by using a balloon catheter. PMID- 2238777 TI - [Favorable long-term prognosis following late recanalization of main branch occlusion of the left coronary artery]. AB - A 52-year-old man presented with an acute anterior myocardial infarction due to total occlusion of the left main coronary artery. Three weeks later a successful recanalization was performed. At an early recoronarography the vessel was patent. Initially existing severe congestive heart failure (NYHA class IV) improved to NYHA class II over 6 months. Three years later the patient is almost without complaints and, at echocardiography, left-ventricular enlargement was clearly declining. PMID- 2238779 TI - [Dependency in the aged]. PMID- 2238780 TI - [Psychosocial guidance of nursing home personnel by group therapy. Basic considerations and initial experience]. AB - Support groups for those professional caregivers who work in homes for the aged are seldom. Focussing on occupational stressors in this profession and the burnout research as a conceptual framework, a support group is introduced. To sustain the social competence and the coping skills of the caregivers are the basic aims of this group. Based on role taking and psychodrama as intervention techniques, outcomes from this group are discussed. Recommendations for future groups as a support system for caregivers in homes for the aged are derived. PMID- 2238781 TI - [Residents and personnel as sources and targets of violence in homes for the aged]. AB - Aspects of prosocial and of violent behaviour among residents, among staff, and between residents and staff of homes for the aged in German-speaking Switzerland and possible determinants were ascertained by mailed questionnaires (N = 205; rate of return: 20%). Prosocial behaviour is dominating but violence in many forms occurs too. Violence correlates with low age of the employees, with a low motivation for continued education, with a low satisfaction with the work situation in many forms, with low life satisfaction, with life problems, with high numbers of inhabitants of the political community, with the size of the home, and with unfavorable conditions of the staff. Correlations between the behaviour of home residents and staff leads to the proposition that violence in one group furthers violence in another group and hinders prosocial behaviour. The report is closed by considerations concerning methodological restrictions and practical consequences. PMID- 2238782 TI - [Memory training in old age: theoretical background and development of an intervention program for nursing home residents]. AB - A survey of the literature reveals that studies providing hard evidence of the effects of training on improvement of cognitive skills in old age focus on highly specialized training measures. To date there are hardly any suitable procedures for memory training that have a broad effect on the consciousness of impaired individuals which would nurture a different attitude towards the entire complex of learning and memory. For this reason a memory training program was developed, aimed at conserving, reactivating, and fostering the cognitive skills of non demented residents of old people's homes. The training program, carried out over a 3-month period, consists of a total of 24, 45-min training units. The first half of the memory training program prompts participants to use as many channels of perception as possible, and thereby, also to employ compensation possibilities. In addition, there are exercises for improving observation and concentration and for understanding the functions of memory on the basis of a simplified model of information processing. The second half of the memory training program focuses on exercises to improve short-term and medium-range retention. The exercises are oriented in content to the daily situations relevant to the residents in which memory performance is expected. The memory training program was used for the first time in a geriatric facility in Mannheim, FRG. Continued use of the program, coupled with an evaluation, is planned as part of a research project in several homes for the elderly in that greater metropolitan area. PMID- 2238783 TI - [Detection of dementia and depression using the Brief Assessment Interview (BAI): results of a reliability and validity study with residents of a nursing home in Mannheim]. AB - Described here is the German version of the Brief Assessment Interview (BAI), an instrument developed originally in the course of the US-UK cross-national studies and designed to compile data on dementia and depression among the elderly. A study in Mannheim, FRG, of residents in an old people's home tested the reliability and validity of the BAI. Raters corresponded to a high degree on both the dementia and depression scales; intraclass coefficients (ICC) amounted to 0.95 and 0.97, respectively. Compared to the interrater reliability, test-retest reliability was somewhat lower (dementia scale: 0.83, depression scale; 0.74), but always significant at the 1% level. The internal consistency of the dementia scale lay between 0.62 and 0.77, and that of the depression scale between 0.78 and 0.92. In evaluating the validity of BAI, results of the dementia and depression scales were compared to the corresponding diagnoses. These independent diagnoses had been made with the aid of the Feighner criteria by the director of the facility, who had special training in psychiatry. The diagnoses yielded a significant relationship (p less than 0.01) between the dementia (r = 0.49) and depression scales (r = 0.60). The BAI also attained sufficiently high values for sensitivity, specificity, and total efficiency. It is, therefore, well suited for use in elderly target groups that are otherwise difficult to assess, and it also affords a high degree of international comparability. PMID- 2238785 TI - [Use of self-rating instruments with elderly hospital patients]. AB - The usefulness of self-rating instruments for measuring the emotionality of elderly and/or physical ill individuals is discussed. Therefore, 99 inpatients of internal wards (mean age: 65) were examined with the German form of the State Trait Anxiety Inventory (Laux et al., 1981). All the problems which arose when the test sheet was filled out were recorded and subsumed into one of the following categories: comprehension problems, problems with the answer categories, answer tendency, problems with layout. As expected, we were able to show that practical problems increase as patients become older. None of the patients over 80 years was able to complete the scale without considerable help in a standardized manner. We recommend to use structured interviews for assessing the emotional state of elderly patients. PMID- 2238784 TI - [Alzheimer's disease: experience, perception and reactions of patients]. AB - Clinical research into Alzheimer's disease has predominantly focused on standardized assessment of cognitive impairment and behavioral changes. The description of feelings and attempts of adaptation of patients with Alzheimer's disease is a neglected area. Here we present five statements, each given by a patient with Alzheimer's disease, and investigate perception and attempts of adaptation contained in these statements. Important consequences for the care of patients with Alzheimer's disease are discussed. PMID- 2238786 TI - Caring for elderly parents in Sweden: the biographies of two groups of elderly and their parents. AB - In this study two sample groups of very old people report on needs for care among their parents. We report on who gave the care and if parents were institutionalized. Information on social class, preferences for care for oneself, etc., was also collected. Comparisons with contemporary data indicate that patterns of care remain historically quite stable, and that experiences of providing care influences one's own preferences many years later. The welfare state seems to have increased the freedom of choice for, especially, the poorer elderly. PMID- 2238787 TI - Direct sectioning of unembedded cartilage: a simple method for microscopical and histochemical studies on chondrocytes and extracellular matrix. AB - On account of the rigidity and compact structure of the hyaline cartilage, unfixed or formaldehyde fixed samples of this tissue can be directly sectioned by using a conventional ultramicrotome and a glass knife. This simple method allows to obtain microscopical sections from unembedded cartilage blocks, which show a well preserved histological structure and are very suitable to carry out morphological and histochemical studies on chondrocytes and cartilaginous matrix. PMID- 2238788 TI - Enzyme histochemical and histological changes in the adult rat kidney after prenatal gentamicin exposure. AB - Treatment of rats between day 15 and 20 of gestation with gentamicin caused histological as well as enzyme histochemical lesions in the kidney of the one year old offspring (F1 generation). Other organs were not significantly affected. Primarily in the female kidney dilated convoluted proximal tubulus with reduced or absent staining for brush border and lysosomal proteases, phosphatases and glycosidases and mitochondrial dehydrogenases were observed. In comparison, glomeruli were less frequently damaged and contained fewer capillary loops or irregularly arranged tissue elements with lowered or no activities for plasma membrane-associated proteases as well as specific and non-specific phosphatases. In addition, the activities of proteases and phosphatases in cortical and medullary endothelial cells of capillaries were reduced or even abolished in the kidney of the female and male F1 generation after treatment of their mothers with gentamicin. PMID- 2238789 TI - Ultrastructural and immunocytochemical study on bursal follicle medulla cells in Gallus domesticus. AB - The use of the monoclonal anti-cytokeratin 6 and 18 antibody Dako CK 1 revealed a marked positivity of reticulo-epithelial cells (REp). Aspecific esterase testing, light microscopy, and electron microscopy were used in order to obtain a comparison between the morphology of the lymphoid follicle medulla and the picture obtained by using the monoclonal antibody CK 1. Results showed that the bursal follicle medulla can be divided into 2 areas: an esterase-positive, cytokeratin-negative centre-medulla, and a more peripheral cytokeratin-positive, esterase-negative area. These 2 regions appear to be separated by a boundary composed of flattened REp cells. Desmosomes were also observed not only among their processes, but also between the latter and the side of the cortico-medullar boundary epithelium which is external with respect to the basal membrane. PMID- 2238790 TI - Endothelial cilia in rat mesenteric arteries and intramyocardial capillaries. AB - We report for the first time the presence of endothelial cilia in rat blood vessels. They are seen in the mesenteric arteries of hypertensive rats and the intramyocardial capillaries of aged rats. The cilia are solitary and have the shape of the "9 + 0" axonemal structure. The processes of the basal foot and the transitional fiber are accompanied by basal bodies. The function of the solitary cilia is obscure. PMID- 2238791 TI - Morphology of Schmidt-Lanterman incisures of human shoulder plexus nerves in ontogenesis. AB - The Schmidt-Lanterman incisures are formed in the phase of "loose" myelin at 15 17 weeks of prenatal development with the formation of nodes of Ranvier. The formation of mature Schmidt-Lanterman incisure is completed in the second foetis period. Schmidt-Lanterman incisures distribution in nerve fibres of young men depends on fibre diameter. In the nerves of elderly people the distribution of the incisures in the internode doesn't depend on a fibre diameter. In the nerves of the elderly men the number of incisures is twice as much as that in the young people. The incisural ultrastructure in human nerve is similar to its structure in other mammals. PMID- 2238792 TI - Morphology of Schmidt-Lanterman incisures of human shoulder plexus nerves. AB - Morphological studies of peripheral human nerves have shown that the number o of Schmidt-Lanterman incisures in an internode is proportional to the fibre diameter. Quantitative and ultrastructural examinations of incisures in the shoulder plexus nerves of the juvenile have proved some common features in the distribution and structure of incisures, characteristic for the nerves of both mammals and people. However, in all probability, in the peripheral nerves of man under certain condition there is a mechanism, leading to a sharp increase of the number of incisures in the internodal segment. PMID- 2238793 TI - Fine structure of camel erythrocytes in relation to its functions. AB - The fine structure of the red cells in Arabian camels was investigated and certain characteristic features were noted. The plasmalemma of camel erythrocytes are tri-laminar, the inner and outer membranes are of high electron density between which is a zone of lesser electron density. No intracellular organelles were observed with the occasional exception of a small number of mitochondria. In the camel erythrocyte, a marginal band consisting of 30-45 microtubules was observed in many cells. Some of the possible functions of the marginal band in camel erythrocytes are discussed. PMID- 2238794 TI - [Immunohistologic studies of the distribution of proliferative compartments in the appendages of adult human skin]. AB - Both, calmodulin (CaM) as well as the antigen Ki67 show a close relationship to cell proliferation. By means of specific antibodies against them, it has become possible to study the spatial distribution of proliferative compartments in tissues. We performed an indirect immunofluorescence study on unfixed frozen sections of human adult skin to gain more informations about the spatial distribution of immunoreactive CaM and Ki67 in skin appendages, i.e. anagen hair follicle, sebaceous and eccrine sweat gland. Two major patterns of immunoreactivity were seen: Type (1) or epidermis-like, which was present in the interfollicular epidermis and the pilosebaceous unit. Type (2) or sweat gland type, which was seen in eccrine sweat glands. Both types disclosed significant differences in the relative number of proliferative cells in S-phase, which might be a consequence of a quiet different tissue architecture. Furthermore, myoepithelial cells of secretory coils were likely to represent mainly SQ-cells. Their immunoreactivity in human skin was quiet different from other parts of eccrine sweat glands suggesting another ontogenetic pathway. PMID- 2238795 TI - Effect of progesterone (norethindrone) only oral contraceptive on mouse uterus--a SEM study. AB - Impact of progesterone (norethindrone) only oral contraceptive (MICRONOR) on mouse uterus was investigated by SEM. The three dimensional SEM photographs revealed that, flat wave like mucous folds of the uterus (control) become more thick and highly convoluted after 50 days of MICRONOR feeding. The uteri became highly secretory as indicated by increased thickness of nonciliated secretory cell population with their increased microvilli. Low doses of norethindrone in combination with circulating estrogen, instead of causing regression, maintained a steady and highly secretory state which may interfere implantation/gamete transport. PMID- 2238796 TI - Luteinization in the atresia of maturing ovarian follicles in mouse. AB - Maturing ovarian follicles undergoing atresia were ultrastructurally analyzed. Using the method of Okros (1968) the process of luteinization was traced, taking place in the basal layer of cells of granulous membrane and in the cells of inner layer of theca interna during the atresia. In the atresia process, numerous electron dense granules arranged in packets and surrounded by tubular mitochondria are observed in the basal cell layer of granulous membrane. A considerable accumulation of the grains of reaction product and the presence of tubular mitochondria are also found in the cells of theca interna. Such a behaviour of those cells can be associated with an enhanced production of steroid hormones (mainly estrogens) in atretic follicles. PMID- 2238797 TI - Ultrastructural studies on the morula in cattle. AB - Embryos at morula stage were ultrastructurally examined. Blastomeres of normal embryos are characterized by the presence of ribosomes, short single and branched cisterns of endoplasmic reticulum, small spherical mitochondria and vacuolar granular structures. An enhanced autophagy and the presence of numerous and large lipid droplets are signs of the beginning degeneration. PMID- 2238798 TI - [Functional disorders of the immune system]. AB - In common with other organ systems in the body the immune system demonstrates functional disturbances which may lead to numerous immunological disorders with grave consequences for the health of the patient. Whenever the complex network of regulation and counter-regulation mechanisms within the defence system is impaired, by hereditary or acquired defects, immunological defect syndromes occur. One of the disorders that has been the object of intensive discussion in this context over the past few years is the acquired immune deficiency syndrome AIDS, a dangerous viral infection that mostly affects the T4 cells, whose helper and inductor function is absolutely essential for successful immunological defence. Furthermore, functional impairment of the antibody-producing plasma cells leads to the heterogeneous group of gammopathies which are characterized by an uncontrolled and excessive proliferation of structurally uniform antibody molecules in the blood. Overreactions of the immune system which wrongly attack endogenous tissue are accredited with causing the so-called auto-immune diseases. The clinical pictures within this group are exceptionally varied, and depend both on the self-antigen that the attack is aimed at as well as the erroneously triggered effector function that is affected. Whenever the immune system reacts disproportionately strongly against otherwise harmless foreign antigens, allergic clinical picture emerge. PMID- 2238799 TI - [Malignant lymphedema]. AB - Malignant lymphatic oedema is due to the obstruction of lymph tracts and lymph nodes by tumour cells. In addition to the necessary cancer therapy and the administration of analgesics physical oedema therapy is the single most effective form of relief which is most gratefully accepted by the patients. The only contraindication to manual lymphatic drainage is transient in the case of isolated local and regional metastatic spread which would still respond to treatment. Thereafter, and in all other conditions involving metastatic spread, there are no contraindications to physical oedema therapy. PMID- 2238800 TI - [Edema caused by isolated hyperthermic perfusion of the extremities]. AB - Isolated extremity perfusion today is an undisputed alternative to amputation and a causal form of therapy for locally and regionally metastasising melanomas. In order to avoid the most serious complications such treatment should only be carried out at special centres. Milder side-effects such as early and late postoperative oedema respond well to drug regimes and manual lymphatic drainage. PMID- 2238801 TI - [A comparison of intermittent compression with single and multi-chamber systems in treatment of secondary arm lymphedema following mastectomy]. AB - In a comparative study 38 patients with secondary unilateral lymphatic oedema after mastectomy were investigated with regard to the efficacy of intermittent compression treatment using uni- or multichamber systems (Jobst and Lymph-a-mat respectively). Although both machines significantly reduce oedema, there is no difference between their reduction capacities. PMID- 2238802 TI - [Iatrogenic damage in sclerotherapy of varicose veins]. PMID- 2238803 TI - [Varicose veins and chronic venous insufficiency--minor disorder or disease? A critical review of the literature]. AB - The controversial question of the incidence and significance of varicoses and chronic venous insufficiency is analysed by a critical review of epidemiological studies. It is seen that many of the results which initially appear to diverge are attributable to different, in part unsatisfactory epidemiological methods; e.g. patient groups of different ages and sex, different interview and examination techniques in addition to, above all, different weighting of varicosis. Thus, studies in general practice showed that the prevalence for varicoses in women was four times that in men; CVI was, in fact, 15 times more frequent than in epidemiological studies. The different weighting of varicoses and chronic venous insufficiency may well be one of the major reasons for the absent "unite de doctrine". PMID- 2238804 TI - [Venous disease and pregnancy]. PMID- 2238805 TI - [The practical aspects of research on heterophasic cavitary digestion]. PMID- 2238806 TI - [Motion sickness: the resonance hypothesis]. PMID- 2238807 TI - [The collateral coronary circulation and the problem of its pharmacological stimulation]. PMID- 2238808 TI - [The molecular organization of the contractile apparatus and the mechanics of muscle contraction]. PMID- 2238809 TI - [The effect of cerebellar structures on the epileptic activity in the brain]. PMID- 2238810 TI - [Stressor immunodeficiencies in man]. PMID- 2238811 TI - [The role of acetaldehyde in the mechanisms of the action of ethanol]. PMID- 2238812 TI - [Chronic venous insufficiency today (a status determination)]. AB - Primary as well as secondary cvi (due to deficiency of the deep venous reflux) is a disease that necessitates a thorough therapy planning and a life-long medical care. Neither operation nor sclerotherapy alone can cure these patients. Active measures must always be combined with conservative procedures such as individually manufactured pressure gradient stockings, occasional intermittent medical treatment of complications and careful guiding of the patients over many years. The first measure is of course a careful establishment of the diagnosis by clinical examination and modern technical methods such as Doppler ultrasound, plethysmography and, in selected cases, phlebography. The therapy concept must consider the advantages and disadvantages of the various methods. A combined treatment in team work with the vascular surgeon may be the starting point, but must always be followed by an intensive life-long guidance of the patients with additional treatments according to necessity. PMID- 2238813 TI - [Duplex ultrasound measurement of morphologic parameters before and following repeated puncture of the femoral artery for intermittent infusion therapy]. AB - In order to estimate morphologic changes of the femoral artery after an intermittent intraarterial infusion therapy duplex scanning was performed before therapy, immediately after a series of 26 (10 to 52) infusions, and 30 weeks after hospital discharge. Minimum and maximum values of internal and external vessel diameter and thickness of wall were estimated in the common femoral artery, superficial femoral artery, and deep femoral artery. The external diameter values and the thickness of wall increased significantly after therapy. After 30 weeks these values decreased but did not reach the initial values. PMID- 2238814 TI - [Doppler ultrasound determination of pressure decrease in model peripheral arterial stenoses]. AB - In a pulsatile in vitro flow model with mounted concentric peripheral arterial stenoses, we compared the mean trans-stenotic pressure difference between pre- and poststenotic segment with the Doppler-estimated mean pressure gradient calculated according to the simplified Bernoulli equation applied over an entire stroke cycle. A close linear correlation was found between Doppler-estimated and invasively measured pressure drop values: Y = 1.13X + 0.47 (r = 0.98, SEE = 1.4 mmHg, n = 16). The Doppler-derived overestimation of the invasively measured mean pressure-drop by an average of 16% (absolute values 2.2 +/- 1.7 mmHg) suggests that in this in vitro model a small part of the kinetic energy of the stenotic jet is recovered distal to the poststenotic turbulences. The difference between both methods is so little that the Doppler-estimated mean pressure drop is acceptable in concentric peripheral model arterial stenoses. PMID- 2238815 TI - [Diagnostic value and criteria for evaluating indirect lymphography in lymphedema]. AB - To evaluate the deciding diagnostic criteria of indirect lymphography in lymphoedema of the leg, 91 investigations were reviewed. 72 examinations were from lymphoedematous legs as judged by clinical appearance and isotopic lymphography and 19 from healthy legs. After subepidermal infusion of adequate water soluble contrast media (e.g. Jotrolan) in healthy legs, 17 from 19 cases showed normal ellipsoid dye-deposits with normally structured lymph-collectors. In two cases pathological lymph-collectors were shown (specificity 89%). In the 72 legs with lymphoedema the most prominent pathological features were altered lymph-collectors and/or dermal backflow. Only two cases revealed a normal pattern (Sensitivity 97%). Indirect lymphography therefore may be recommended as a sensitive but less specific diagnostic tool for proving lymphoedema in a suspected clinical situation. PMID- 2238816 TI - Venous haemodynamics of the upper extremity after subclavian vein thrombosis. AB - Late post-thrombotic complaints after subclavian vein thrombosis are reported with highly varying frequencies (8-80% severe disability). The therapeutic approach depends partly on this frequency. With the aim to evaluate late sequelae a questionnaire was answered by 26 patients with arm-shoulder symptoms leading to arm phlebography, but where the examination did not reveal any thrombi. 65% had remaining symptoms 2-9 years after the examination. 3 had to change profession. 36 patients with phlebographically shown subclavian vein thrombosis answered the same questionnaire. Only 9 (25%) had remaining symptoms and in 4 it was classified as mild, in 4 as moderate and only in 1 patient as severe leading to change of profession. Venous haemodynamics in the upper extremity were also studied in 3 groups of patients; I) healthy volunteers (n = 16 arms), II) patients with arm-shoulder disabilities with negative arm phlebography (n = 7 disabled arms, n = 7 non-disabled arms), III) patients with phlebographically verified subclavian vein thrombi (n = 10 arms with DVT, n = 8 arms without DVT). Strain gauge plethysmography was used measuring venous capacity and maximal venous outflow. Venous pressure measurements were made both with the arms in a resting position and in a military position with and without work-load. Repeat phlebography of arms with symptoms were made. Maximal venous outflow was significantly lower in arms with previous subclavian vein thrombi (p less than 0.05) and venous pressure measurements with the arm in military position was significantly higher in those arms. However, no correlation between these measurements and the degree of arm disability was noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238817 TI - Follow-up of the long-term effect of intraarterial vasodilator administration in patients with PAOD by means of changes in resting arterial and venous lactate and pyruvate levels, and in ABB parameters. AB - The aim of the study was to assess, on the basis of changes in the resting arterial and venous values and arteriovenous difference of pH, pCO2, pO2, lactate, pyruvate and the lactate/pyruvate ratio in blood collected from the common femoral artery and vein before and after therapy, and at 4 weeks after therapy, the long-term effect of intraarterial vasodilator administration in 42 lower extremities with the chronic ischaemic syndrome in stages IIb, III and IV according to Fontaine. Ten intraarterial vasodilator infusions containing 300 mg trimecaine and 60 mg papaverine in 200 ml of saline led to an increase in oxygen extraction from circulating blood, as demonstrated by a statistically significant rise in arteriovenous pO2 difference persisting as long as 4 weeks after termination of therapy. The finding of increased CO2 release and the permanent drop in venous lactate levels suggest stimulation of aerobic metabolism of the chronically ischaemic tissue of the lower extremity induced by intraarterial vasodilator administration. PMID- 2238818 TI - Reactive oxygen metabolites in peripheral arterial occlusive disease. AB - Plasma oxidant activity (marker of reactive oxygen metabolites) and the unfractionated leucocyte filterability rate (determined through 5 micron pore diameter Nuclepore filters, using a positive pressure system) were monitored in 15 stage II peripheral vascular disease (PVD) patients before and after ischaemia was induced by treadmill exercise (12 degrees slope/2 km/hour). Plasma oxidant activity increased (+ 115%) significantly (p less than 0.001) at the maximum walking time, correlating (r = 0.79) with a significant (p less than 0.001) impairment (+23%) in the unfractionated leucocyte filterability rate. At the transcutaneous oxygen pressure (tcPO2) half recovery time the plasma oxidant activity approached basal values but the unfractionated leucocyte filterability rate remained significantly (p less than 0.001) impaired (+16%). It returned to basal values at the full tcPO2 recovery time. These results show reactive oxygen metabolites are released during ischaemia of the lower limbs and are correlated with a significant impairment in the flow properties of leucocytes. PMID- 2238819 TI - [Vasa vasorum of subcutaneous veins and lymph vessels]. AB - After intraarterial ink-injection the vasa vasorum of veins and lymphatic vessels in adults, dead born children and fetuses were demonstrated micropreparatorily. In their walls the larger veins of the saphena system possess a capillary network corresponding to the connective tissue and muscle structures/patterns in the vessel wall. No vasa vasorum could be found in the subcutaneous veins less than 1 mm in diameter. The lymphatic vessels of the inner prefascial bundle show a one dimensional capillary network in the outer layers of the wall. Like the vasa vasorum of the saphena system it develops in the second half of fetal life. PMID- 2238820 TI - Diabetic microangiopathy treated with elastic compression--a microcirculatory evaluation using laser-Doppler flowmetry, transcutaneous PO2/PCO2 and capillary permeability measurements. AB - One hundred and forty patients with diabetic microangiopathy were studied by laser-Doppler flowmetry--measuring skin blood flow at rest (RF) and the venoarteriolar response (VAR)--by transcutaneous PO2 and PCO2 measurements and by evaluation of capillary permeability (rate of ankle swelling = RAS). Seventy were treated for 12 months with below-knee, elastic stockings. Seventy patients were left without compression acting as a control group. After 5 and 12 months there were no significant changes in the control group. However there was a significant improvement of microcirculatory parameters in patients treated with elastic compression. RF (increased at the beginning of the study) decreased. The VAR (impaired at the beginning of the study) improved significantly. PO2 (increased after treatment) and PCO2 (decreased) were also positively changed by elastic stockings. The abnormally increased capillary permeability was also improved. Elastic compression seems to be useful in diabetic microangiopathy improving microcirculatory parameters and decreasing capillary permeability and edema. However further studies, treating with elastic compression more patients for longer periods, are needed to confirm the positive effects of elastic stockings in improving diabetic microangiopathy and in slowing down its rate of progression. PMID- 2238821 TI - Gluteal necrosis after acute ischemia of the internal iliac arteries. AB - Ligation of the internal iliac artery mostly remains without consequences because of the well established collateral network. In patients with compromised collateral circulation however, acute interruption of both hypogastric arteries during aorto-iliac surgery or transluminal embolisation can lead to necrosis of the gluteal muscles and other adjacent organs (rectum, bladder, lumbosacral plexus). Experience with 3 similar cases after aorto-iliac surgery demonstrates two main intraoperative mechanisms: 1. Embolisation, 2. Ligature of both internal iliac arteries in patients with compromised arteriosclerotic collaterals. Despite of adequate therapy, mortality is over 70%. The most important feature during aorto-iliac operations is to preserve at least one internal iliac artery by either reimplantation of the main stem or by an additional bypass to this artery. PMID- 2238822 TI - White fingers after excessive motorcycle driving: a case report. AB - An 18-year-old male presented with Raynaud's phenomenon which was found to be caused by occlusion of the proper palmar digital arteries on the right hand and obstruction of the superficial palmar arterial arch on the left hand. These lesions in the arteries of both hands resemble those found in patients with vibration-induced white fingers such as in mine or foundry workers. The only likely cause for the pathological vascular findings in our patient was an exposure to vibration due to excessive off-street motorcycle driving. Therapy with intraarterial prostaglandins resolved the ischemic syndrome but it promptly recurred when the patient resumed motor cycle driving. Therefore, we suggest that excessive cross country motor cycle driving may cause vibration-induced white fingers. PMID- 2238824 TI - The searching sun: the Lyeime Movement--crisis, tragic events and folie a deux in the Papua New Guinea highlands. AB - An historical crisis movement from the highlands of Papua New Guinea re-examined from a psychiatric point of view raises the possibility that the two leaders suffered from mental disorder. The principal prophet apparently had paranoid schizophrenia. As a middle-aged man he established the cult which spread rapidly in the Enga area in the 1940s at the time of first contact with outsiders. A surviving brother, who had also been an important figure in the movement, suffered a similar illness--an example of shared psychotic disorder or folie a deux. PMID- 2238825 TI - Post-traumatic stress disorder (PTSD): a review of the literature and report on nine cases seen in Papua New Guinea. AB - In 1980 the American Psychiatric Association published the third edition of the Diagnostic and Statistics Manual (DSM-III). The DSM-III introduced post-traumatic stress disorder (PTSD) as a new diagnostic category in psychiatry. This provided firstly a framework for studying the consequences of extremely stressful life events, and secondly it has stimulated a substantial number of research publications in this area. The purpose of this paper is to review the literature on PTSD and to report nine cases seen in Papua New Guinea over a period of nine months. PMID- 2238823 TI - An assessment of acetylator polymorphism and its relevance in Papua New Guinea. AB - A number of clinically useful drugs such as isoniazid, sulphonamides, procainamide and dapsone are rapidly inactivated and eliminated metabolically by an acetyltransferase enzyme. The rate of elimination of these drugs is dependent upon the level of enzymatic activity, which is known to be genetically determined and exhibits ethnic and geographical variation. The study of acetylation polymorphism therefore is important especially in view of its effect on drug efficacy and toxicity. Limited information is available on the acetylation status of Papua New Guineans. Studies conducted so far have revealed an unusually high frequency of the rapid acetylator phenotype (greater than 90%) in certain populations. This study confirms the previous observations and reviews the world wide distribution pattern of acetylation polymorphism. PMID- 2238826 TI - The first hundred referrals to a new consultation-liaison psychiatric service at the Port Moresby General Hospital, Papua New Guinea. AB - Research workers in Africa have shown that psychiatric morbidity is widespread, with prevalence rates ranging between 20 and 50% of the primary health care clinic attendance. In September 1987 a new consultation-liaison psychiatric service was started at the Port Moresby General Hospital. The results of a descriptive study of the first hundred referrals to the service are presented and discussed. The sources of referral were internal medicine (83%), general surgery (11%) and obstetrics and gynaecology (6%). There were no referrals from the division of paediatrics in this study. It was concluded that the results have demonstrated acceptance of the consultation-liaison psychiatric service by non psychiatric specialist colleagues. PMID- 2238827 TI - The effect of betel nut on human performance. AB - The effects of low doses of betel nut on early-stage visual information processing were examined, using a cross-over experimental design. Three assessment measures were used, critical flicker fusion (an index of the efficiency of the visual processing system), heart rate, and analogue scales of subjective alertness. Only heart rate was shown to be significantly elevated, immediately following betel nut administration. From these results, it was concluded that there is no evidence to suggest that betel nut usage facilitates visual information processing at low-dose levels in habituated subjects, but there is some evidence that peripheral stimulation occurs. PMID- 2238828 TI - Introducing the concept of amae. PMID- 2238829 TI - Fatal post-splenectomy sepsis in a Papua New Guinean highlander. AB - A fatal case of overwhelming post-splenectomy sepsis (OPSS) occurring 5 years after splenectomy for trauma in a Papua New Guinean highlander is presented. The diagnosis of pneumococcal infection was made from a peripheral blood smear. The finding of OPSS in Papua New Guinea is cited as additional evidence in favour of a policy of conservative management, where possible, of ruptured spleen. PMID- 2238830 TI - A case of pseudoanaphylactic reaction to intramuscular procaine penicillin G (Hoigne's syndrome). AB - A personal record of a pseudoanaphylactic reaction to procaine penicillin G is presented, together with a brief discussion of the topic. Since procaine penicillin is widely used in Papua New Guinea the reaction may be more common than is generally realized. The reaction is not a true anaphylaxis and is probably caused by the procaine component after inadvertent intravenous injection of the drug. PMID- 2238831 TI - Neonatal septicaemia. PMID- 2238832 TI - The impact of acquired immunodeficiency syndrome (AIDS) on tuberculosis control in Papua New Guinea. PMID- 2238833 TI - Cancer on the increase in Papua New Guinea: the failure of preventive measures. PMID- 2238835 TI - The monitoring of foodhandlers in Papua New Guinea. AB - In early 1987 guidelines were re-enforced for pre-employment medicals and 6 monthly health checks on foodhandlers in the Ok Tedi mining project in Papua New Guinea. The health monitoring program was stepped up as a result of two typhoid cases imported from the highlands and catering subcontractors failing to comply with the necessary pre-placement medicals for foodhandlers. Highlanders made up 28% (49/174) of the Ok Tedi catering department's workforce in 1987. The initial screen of 155 foodhandlers and 85 non-foodhandlers in February 1987 showed 6-7% of each group asymptomatically harbouring Salmonella spp. or Shigella spp. A second survey of 160 foodhandlers in August, including private fast-food establishments, detected only one Shigella boydii infection at a local fast-food takeaway shop. Salmonella typhi was not detected in foodhandlers but was isolated from two non-foodhandlers recently returned from the highlands; in one case this resulted in a contact becoming infected at Tabubil. Infected persons were treated accordingly and foodhandlers were relieved of catering duties until follow-up cultures proved negative. Helminth infections were detected in 38% (309/811) of the stool samples examined. The low prevalence of Ascaris lumbricoides (2.5%) and Trichuris trichiura (1.1%) acquired locally, and a significant difference compared with outside groups supports the view that these species have recently been introduced to the North Fly (Ok Tedi) region. The majority of all Ascaris and Trichuris infections detected (61% and 73%, respectively) were found in highlanders, infection rates ranging from 3 to 15% depending on province of origin. Infections were treated accordingly to prevent possible transmission via food.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238834 TI - Diethylcarbamazine in the control of bancroftian filariasis in the highly endemic Ok Tedi area of Papua New Guinea: phase 1. AB - The effects of a well-spaced diethylcarbamazine (DEC) mass drug application in areas highly endemic for Wuchereria bancrofti in Papua New Guinea are not known. In 1986 a semi-annual single-dose 6 mg/kg body weight administration of DEC was initiated in the Ok Tedi area of Western Province, Papua New Guinea. The rate of bancroftian filariasis in the area was 39%. Within two years the rate of detectable microfilaraemia was reduced from 31% to 11% in the treated group. The mean blood density of the parasite was reduced from 79 to 19 microfilariae per 20 microliters. A survey of untreated villages in the immediate area (not surveyed before 1988) showed a filariasis rate of 39%. A 14-fold difference in the total microfilaraemia count was noted between the two groups when 1988 data were compared. A reduction in the annual rate of filariasis may be monitored through a well-established passive case detection program for malaria. The DEC treatment program was well accepted despite side-effects encountered in 20% of the treated population early on in the program. The success of the 2-year Phase 1 program has expanded into an annual single-dose administration of DEC over a larger area. PMID- 2238836 TI - Identification of irradiated foods by the thermoluminescence of mineral contamination. AB - This investigation assessed the radiation-induced thermoluminescence (TL) of food minerals for identifying irradiated foods. Mineral contamination, rather than the inherent mineral content, of foods was studied. Positive identification of foods given 1-10-kGy doses depends on the contents and composition of the mineral contamination and the time span between irradiation and TL analysis. All 20 irradiated spice and herb samples could be identified without comparing them with unirradiated material. Three out of 60 lots of spices and herbs examined so far were so pure that the mineral contents were too low to allow TL analysis. If the soil where potatoes are grown contains feldspars, sprout inhibition treatment with 100-200-Gy doses can also be detected for up to one year, using the 90-250 degrees C low-temperature part of the TL spectrum for evaluation. PMID- 2238837 TI - The effects of gamma-irradiation on some pure aroma compounds of spices. AB - Chemical changes due to gamma-irradiation were investigated in 11 pure aroma compounds typically found in spices. Samples were irradiated with doses of 0, 10, and 50 kGy. The irradiation source was 60Co. Irradiated samples and unirradiated controls were analyzed by gas chromatography alone and coupled with mass spectrometry. Significant changes due to the irradiation occurred only in (+/-) linalool and alpha-terpineol, which are typical components of, for example, coriander and bay leaf. Their total amounts decreased by about 4-13% and some minor peaks increased as a result of irradiation. However, different results may be obtained when the spices themselves are irradiated. PMID- 2238838 TI - [Chronic use of analgesics]. AB - Quantitative aspects of longterm analgesic intake are presented, based on a case control-study on the relation between regular analgesic intake and endstage renal failure in the area of West Berlin (1984-86). Lifetime analgesic consumption of more than 1000 persons were investigated. A total of 285 longterm analgesic users (185 cases = 35.8%; 100 controls = 19.3%) were detected. An odd ratio of 2.44 (95% CI: 1.77-3.39) was computed. Regular analgesic intake was defined as an intake of at least 15 analgesic doses per month continuously over a period of at least 12 months. 90% of the regular users preferred mixed analgesics compounds, in most cases with the psychotropic additive caffeine. PMID- 2238839 TI - [General practitioners and internists prescribe psychopharmaceutic drugs]. AB - An epidemiological study using data from a local German health insurance fund on the psychotropic drug prescription of physicians and the drug utilisation of their patients is presented. Taking a sample of 280 out-patients, descriptive methods are presented (defined daily dose (DDD), prescribed daily dose (PDD), active-agent-oriented classification of drugs, therapy-oriented classification of diagnoses). The following questions are answered by this study: Which patients with which indication received which dosage of which psychotropic drug for how long from which physicians? The patient-based structure of the data, taking into account the prescriptions of all physicians allows the course of therapies and the study of overall psychotropic medication. Prevalences estimates concerning the patients are also possible. Our results are compared with those of similar pharmaco-epidemiological studies; the difference in prevalence estimates, as well as advantages and possible disadvantages arising from the use of such secondary data base, are discussed. PMID- 2238840 TI - Patients compliance in an early detection program for upper aero-digestive tract tumours in north-eastern Italy. AB - An early detection program for tumours of the upper respiratory and digestive tract has been conducted from December, 1988 to May, 1989 in the Friuli Venezia Giulia region, Northeastern Italy. This region shows very high mortality rates for cancers in these sites. Six hundred seventy-one high risk patients (i e habitual smokers and/or drinkers) were referred to Ear, Nose and Throat (ENT) specialists from 16 General Practitioners (GPs) for a free examination as part of the screening program. Four hundred thirty-six patients underwent the visit (65%) with fifty-five precancerous lesions and eight epithelial tumours detected among them. This program appears to have accomplished its aims of establishing a closer relationship between GPs and ENT specialists, discovering early cancerous and precancerous lesions, and targeting high risk patients with an educational message against smoking and heavy drinking. PMID- 2238842 TI - [Butter versus margarine?]. PMID- 2238841 TI - [Reasons for athletic activity versus inactivity of urban population of Basel Stadt 1988]. AB - A representative sample of 778 inhabitants of Canton Basel-Stadt aged 16 to 75 years were asked about their exercise habits and reasons for participating in or abstaining from sports (Response rate: 81%). 56% of the responders took part in a sport more than once a month; the percentage was higher among younger adults and markedly lower among obese subjects. For 27% of the "active" respondents, the most important single motivation for sports was "fun, pleasure und well-being", in 20% of the cases "fitness", in 16% "health" and in 12% "compensation for work and relaxation". For 32% of the "inactive" group, the main reason for abstaining from sports was "lack of time", for 22% "no interest" and in 16% of the cases "sickness or disability"; "no clubs or sports-facilities" was hardly ever mentioned as a reason for being physically inactive (1%). Some significant differences were found when sociodemographic subgroups were analysed. For example, "health" was more often given as a reason for sports by the elderly, and "compensation for work and relaxation" was more often mentioned as the level of education rose. "Lack of time" was a more frequent reason for being physically inactive among young adults, whereas "sickness" was more important among the elderly. A better knowledge of the relative importance of the motivation for leisure time physical activity is likely to be significant for effective sports promotion. PMID- 2238843 TI - [Precipitating factors for shunt insufficiency in post-hemorrhagic hydrocephalus in the premature infant]. AB - Between January 1984 and March 1989 twenty-seven low birth weight infants (mean birth weight 1351 gm, mean gestational age 30 weeks) required shunts after development of a posthaemorrhagic hydrocephalus. Revision of the shunt occurred in 78% of the patients with a range of 1 to 11 revisions. Obstruction of the ventricular catheter was the main cause of mechanical complications that occurred in 75%. Preterm infants weighing less than 1000 gm revealed an enormous infection rate of 71%. Initial shunt placement in the first 8 weeks of life was more likely to need shunt revision (94%) than that placed at older age (44%). There was no difference between the type of shunt and percentage of shunt revision, but the Heyer-Schulte system in comparison with the Codman Uni shunt was more likely to have mechanical complications. Infants with Grade IV haemorrhage required the same percentage of revisions as those with Grade III haemorrhage. There was no association between preoperative therapy and the need for shunt revision. A great amount of erythrocytes and very low glucose levels in the preoperative CSF were more likely to predict shunt revision than predicted by the CSF protein. PMID- 2238844 TI - [Esophageal atresia and quality of life]. AB - To evaluate the quality of life of patients with oesophageal atresia we studied 122 questionnaires about children operated on in several centres of the Federal Republic of Germany. On the basis of this information, the literature, and our own cases, we found that early childhood is complicated by operations, dilatations, difficulties in swallowing and frequent pulmonary infections. These problems improved in most cases during the first years of life. Later on the quality of life can be regarded as good. PMID- 2238845 TI - The fate of swallowed button batteries in children. AB - The method of treatment and fate of 41 button batteries ingested by 34 children were analysed; 31 batteries were in the stomach and 10 beyond the pylorus. In 31 batteries situated in the stomach, removal by magnet tube technique was attempted in 30 batteries, 25 being successfully taken out, while 5 failed passing through the pylorus at the duodenum. One was removed endoscopically, since a magnet tube was not available. The remaining 10 batteries in 10 children were found at different levels from the duodenum to the rectum. In addition, 5 batteries were pushed down from the stomach during magnet tube removal. These 15 batteries, located in the intestine were excreted during 35 hours. In contrast to other asymptomatic foreign bodies that are allowed to pass through the GI tract spontaneously, we feel that button batteries should be removed by magnet tube technique to avoid complications such as GI tract perforation with associated bleeding, possible mercury poisoning and burns. Magnet tube removal is a simple and safety method requiring neither anaesthesia nor admission. PMID- 2238846 TI - [Surgical therapy of malrotations in childhood]. AB - From a total of 174 children treated with malrotations from 1971 to 1988, 148 could be evaluated for long-term results of surgical treatment. The various modalities of treatment were: no correction, dissection of Ladd's bands only, caecoascendopexy, Ladd's procedure and the so-called total correction. Comparing the late results in children with and without correction it was found that those without correction, i.e. without pexy, had to be reoperated in 17% of the cases, whereas the totally corrected children required reoperation in 8% of the cases only. Corrected cases needed to be admitted but not operated later because of pain, constipation, vomiting or poor weight gain in 23%, the uncorrected ones in 6%. Likewise, corrected malrotations resulted in complaints in 27% in contrast to the noncorrected ones in 9%. The conclusion is that total correction results in fewer reoperations but in more symptoms not requiring surgery. PMID- 2238847 TI - Intussusception complicated by bowel perforation during hydrostatic reduction. AB - Most perforations of the bowel during attempt at hydrostatic reduction of intussusception occur in an area of localised infarction in the normal transverse or left colon. An animal model of intussusception was used to find indications for the cause of this phenomenon. We submitted the intussuscipiens of 10 strangulated intussusceptions in 6 dogs to a histological examination. In 6 of 10 intussusceptions we found ischaemic changes in the mucosa of the intussuscipiens. In 3 cases these lesions were multiple. All lesions were found in locations where there was a close contact between the intussusceptum and the intussuscipiens. We did not find signs of impaired circulation of the whole intussuscipiens. We conclude that our findings give an indication that perforation of the intussuscipiens during attempt at hydrostatic reduction occurs through areas of localised ischaemic infarction on the basis of direct pressure by the intussusceptum. PMID- 2238848 TI - Air reduction for intussusception in infancy and childhood: ultrasonographic diagnosis and management without X-ray exposure. AB - For the treatment of uncomplicated intussusception in infants and children, we attempted air reduction without x-ray study to avoid the genetic and carcinogenic effects of radiation. Intussusception could generally be diagnosed by ultrasonography in addition to the history and typical clinical signs without using a barium enema. The success of reduction could also be safely evaluated from the disappearance of both the characteristic sonographic target sign and the abdominal palpable mass, and improvement in the general condition 2 or 3 hours after completing this procedure. This simple, cheap and clean reduction method was applied to 127 patients under strict indications and sedation with diazepam. The successful reduction rate was high (90.6%) and equal to that by hydrostatic reduction. Accordingly, this procedure appears to be safely applicable to the management of uncomplicated intussusception in infancy and childhood. PMID- 2238849 TI - Surgery in unilateral multicystic kidney. AB - During a 15-year period 29 patients were treated for unilateral multicystic kidney. The diagnosis was obtained from antenatal ultrasonography in 17 cases, investigation of an abdominal mass at routine palpation in 10, UTI investigation in 1 and uraemia investigation in 1. Eleven patients had associated malformations. Further investigations included ultrasonography, intravenous pyelography, micturition uretrocystography and in a few cases computed tomography and Dimercapto-succinic acid (DMSA) scan. Percutaneous pyelography was performed in 9 cases. Twenty-six children were operated on and 3 were not operated, of which 1 with severe cardiac malformations, died. The age at operation was under 6 months in 14 cases and between 6 and 12 months in 8. Four children developed hypertension preoperatively but the hypertension disappeared within 1 week postoperatively in all cases. The indication for surgery in unilateral multicystic kidney seems to be clear if the patient is symptomatic. In the asymptomatic patient, the complications of a remaining multicystic kidney like hypertension, malignancy, infection and pain suggest a surgical approach at around 6 months of age. PMID- 2238850 TI - Current management of childhood neuropathic bladder: review of 156 cases. AB - Management of neuropathic bladder aims to maintain renal function and to secure appliance-free continence; because of recent advances, both objectives are theoretically attainable. Our present scheme of management, based upon preliminary video-urodynamic assessment, is outlined. In the years 1984-1988 we treated 156 children suffering from neuropathic bladder. In 5 per cent of cases the upper renal tracts have deteriorated on treatment; in patients presenting with upper tract dilatation, improvement has been obtained in 68 per cent. A quarter of the patients were considered too generally disabled to achieve appliance-free continence; these have been managed by penile appliance, indwelling urethral catheter or, occasionally, urinary diversion. For three quarters of the patients, most ambulant, appliance-free continence was the goal; 68 per cent have been managed nonsurgically and 32 per cent surgically. Reliable day-time continence has been achieved in 78 per cent of the former and 86 per cent of the latter, 80 per cent overall. PMID- 2238851 TI - Tissue expansion facilitates operation of large myelomeningoceles. AB - Two children had delayed operations for large myelomeningoceles. As a preparatory operation one silicon tissue expander was inserted on each side of the lesion and successively inflated by weekly injections of saline. After an expansion time of 5 to 6 weeks the definitive procedure was performed. The newly formed fibrous capsule greatly facilitated the reconstruction of the spinal canal. The surplus of skin and subcutaneous tissue allowed the large defects to be easily close in the midline. Both children managed quite well postoperatively. PMID- 2238852 TI - Postoperative recurrence of splenic epithelial cyst; treatment with subtotal splenectomy. AB - Three children were operated upon for congenital epithelial cysts of the spleen in the five-year period 1983-1987. Their mean age was 9.8 +/- 2.3 years. Two of them were boys. They comprise 1.6% of the surgical pathology of the spleen in our hospital, which is a Reference Centre for congenital haemolytic diseases. Two of the children had been suffering from intermittent colic pain in the left hypochondrium with a tender palpable mass for a short while to the present day. The third patient was asymptomatic; a splenic cyst with calcification of its wall was accidentally revealed by a plain x-ray of the abdomen. Contrast gastrointestinal studies and intravenous pyelography helped us with the diagnosis; they indicated a splenic mass that caused visceral displacement adjacent to the spleen. Ultrasonography proved the cystic nature of the enlargement of the spleen in all the cases. Marsupialization was performed in one patient and removal of the cysts in the other two. All three patients were followed up and re-checked 1-5 years postoperatively (May-June 1988). In one boy who underwent removal of the cyst four years ago, recurrence of the splenic cyst was revealed by ultrasonography, CT scan and radionuclide scan. Subtotal splenectomy was performed. The remaining upper pole is supplied with blood by the short gastric arteries. The recurrence was attributed to coexistence of invisible tiny cysts that had remained in the splenic tissue after the dissection of the major cyst during the previous operation. Subtotal splenectomy is an acceptable alternative procedure for splenic cysts. PMID- 2238853 TI - [Mediastinal sequestration with ectopic pancreatic tissue]. AB - We report on a five-year-old patient with a chronic pneumonia of the upper left lobe of the lung, in whom a broncho-enteric sequestration with ectopic pancreas was found in the mediastinum. Reviewing the literature, different theories on the embryogenesis of this extremely rare anomaly are discussed. PMID- 2238854 TI - Primary Burkitt's lymphoma of the appendix. AB - Appendicitis is a very rare presenting symptom of abdominal Burkitt's lymphoma. Only four cases have previously been identified in the literature, all of them males. This is the first reported case of a female as well as the youngest and is representative of the therapeutic considerations in this unusual manifestation of the disease. PMID- 2238855 TI - Accessory scrotum: report of a case. AB - Perineal ectopic (accessory) scrotum is an uncommon anomaly. We could trace only 5 such cases reported in the literature (8, 10, 11). A case of accessory scrotum and glandular hypospadias has been presented and discussed. PMID- 2238857 TI - Oesophageal rupture due to air-blast injury in children: case report and review of the literature. AB - Perforation of the oesophagus is a surgical emergency that is usually lethal if untreated and commonly fatal if treatment is delayed. The most common type of trauma causing oesophageal perforation is a penetrating injury. Oesophageal ruptures due to external blunt or air-blast injuries are very rare. We report for the first time a case of oesophageal rupture related to air-blast injury to the chest and upper abdomen in a child. PMID- 2238856 TI - Accessory scrotum with lipoma in an infant. AB - We report on a 2-year-old male infant with accessory scrotum with lipoma presenting a perineal mass. Preoperatively no abnormality in the urinary tract and the anorectum was demonstrated. The tumour was resected and perineoplasty was performed. The resected specimen histologically revealed lipoma with tissue suggestive of scrotum. The patient recovered well and was discharged with no clinical complaints. This rare congenital anomaly is described in this paper. The slight continuity between the left scrotum and an accessory scrotal tissue in this case may suggest that this rare anomaly was derived from some abnormality in the migration of precursor tissue of scrotum. PMID- 2238858 TI - [Inflammatory changes in the urogenital tract and therapeutic possibilities in the course of adjuvant disease in the male rat]. AB - The adjuvant disease of the rat is an experimental disease, not only important as an arthritis model, but also as an "urethritis model" in clinical and therapeutical respects. The polyarthritic syndrome in rats following injection of Freund's adjuvant also shows regularly involvement of the genitourinary system. Urethritis, cavernitis, and balanitis are common inflammatory manifestations of the penis, which can mostly be observed. In the peritesticular and periepididymal fat, granulomata and nonspecific inflammatory reactions do occur. Prostata, bladder, kidneys, testes, and epididymis are seldom involved in the inflammatory process. This therapeutical study demonstrated clearly that acetylsalicylic acid (dosage: 80 mg/kg BW/day) cannot be of benefit for these changes. However, it was possible to significantly influence the inflammatory changes by using prednisolone (dosage: 1.5 mg/kg BW/day). PMID- 2238859 TI - [Pharmacokinetic study of percutaneous absorption of salicylic acid from baths with salicylate methyl ester and salicylic acid]. AB - Percutaneous uptake of methyl salicylate was investigated by use of Leukona Rheumabad (Dr. Atzinger) in 10 volunteers. Percutaneous uptake of salicylic acid was investigated by use of Contrheuma-Bad (Spitzner) in 15 volunteers. By use of bathing concentration of 0.03 g/l of methyl salicylate, plasma levels of 220-820 ng/ml were found 1 h after beginning, and 46-193 ng/ml after 6 h. 2.3-8.7 mg of salicyluric acid was eliminated on the first day, and 0.47 to 1.48 mg on the second day. By use of bathing concentration of 0.33 g/l of salicylic acid constant plasma levels of 10 +/- 1.27 ng/ml were found in a period of 24 h. The renal elimination of 0.92 +/- 0.14 at first day, 0.72 +/- 0.11 at second day, and 0.50 +/- 0.08 mg salicyluric acid at third day was found. Salicylic acid was eliminated 0.086 +/- 0.009 resp. 0.079 +/- 0.007 resp. 0.043 +/- 0.011 mg by those days. The half-time of elimination in urine after methyl salicylate bathing is (as with injected salicylic acid) between 2.4 to 4 h. Conversely half-time of elimination in urine by salicylic acid bathing is between 30 to 50 h, and is greater with salicylic acid bathing than with other application forms. This is in agreement with earlier examinations and results which point out the deposition of salicylic acid in skin. Any definitive deposition of salicylic acid in skin by methyl salicylate bathing was not found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238860 TI - Joint manifestations of Lyme borreliosis in Czechoslovakian patients. AB - Involvement of the musculoskeletal system in 50 Lyme borreliosis patients seen in Czechoslovakia is described. Thirty-three patients reported tick bites or that they had removed a tick, four patients had been bitten by some other insect. Skin reaction following tick bite were found in 29 patients. Neurologic involvements have been described in 40 subjects. In one patient complete heart block developed after ECM, so that a permanent pacemaker was necessary for two weeks. Mainly three types of involvement of the musculoskeletal system were observed, mostly as intermittent episodes of arthralgia or migratory musculoskeletal pain. In 37 patients brief attacks of monoarthritis or asymmetrical oligoarthritis were seen, chiefly of intermittent subacute course. Chronic arthritis was diagnosed in seven cases, sacroiliitis in four patients. The authors discuss differential diagnosis, especially in patients with chronic joint involvement. PMID- 2238861 TI - [The HLA system and rheumatoid arthritis]. AB - Recent developments in molecular biology allow a more detailed description of and insight into the interaction between T-cell receptor, antigen/peptide, and MHC gene products. These advances also provide a better approach to understanding the molecular genetics of susceptibility to certain diseases. This review tries to interpret MHC structure/function relationships, using rheumatoid arthritis as a paradigm. The following aspects are of special importance: Most likely MHC class II gene products are directly involved in the pathogenic process and are not only to be considered as "markers". Susceptibility to rheumatoid arthritis is not associated with a single serologically defined HLA-specificity (e.g., HLA-DR4). However, there is substantial evidence that shared functional epitopes on different MHC molecules (e.g., HLA-DR1 and HLA-DR4 subtypes) confer risk for rheumatoid arthritis. PMID- 2238862 TI - [Destructive spondylopathy in chondrocalcinosis ("pseudospondylodiscitis")]. AB - A case of degenerative spondylopathy in chondrocalcinosis (pseudospondylo discitis) is presented. The incidence of vertebral involvement in chondrocalcinosis reported in the literature is reviewed. In approximately 4-10% of all cases of chondrocalcinosis the vertebral column is involved as well. Especially in elderly patients, a differential diagnosis based on clinical, radiological and laboratory findings must include infectious spondylodiscitis. In the presence of additional degenerative spondylolisthesis, as well as radiculopathy and/or symptoms of spinal stenosis, surgery is often performed. However, there are cases reported in which improvement occurs after spontaneous vertebral fusion without surgical intervention. If any vertebral change is detected that is suggestive of chondrocalcinosis, even in asymptomatic patients, it is recommended to obtain radiographs of other joints, for example, the knee and wrist, which are frequently also involved in chondrocalcinosis. PMID- 2238863 TI - [Diabetic osteoarthropathy of the foot]. AB - Neuropathic joint disease (described by J.M. Charcot in 1868) is now most commonly seen in patients with diabetic mellitus. We present a patient suffering from a characteristic diabetic neuro-arthropathy of the foot. We report the clinical features, roentgenographic signs, new diagnostic possibilities, and treatment. PMID- 2238864 TI - [Causality of neurotic and psychosomatic diseases]. PMID- 2238865 TI - [Disputation of the manuscript by W.Brautigam: causality of neurotic and psychological dieases]. PMID- 2238866 TI - [Predisposition and environment. Remarks on W. Brautigam's "Causality in neurotic and psychosomatic diseases"]. PMID- 2238867 TI - [Thoughts on the article by W. Brautigam: Causality in neurotic and psychosomatic diseases]. PMID- 2238868 TI - [The tension area practice/theory in medicine. Commentary on the article from Walter Brautigam]. PMID- 2238869 TI - [Opinion on the article by Prof. Dr. W. Brautigam. Causality in neurotic and psychosomatic diseases]. PMID- 2238870 TI - [Comments on " Causality in neurotic and psychosomatic diseases" from Walter Brautigam]. PMID- 2238871 TI - [Structural analysis of social behavior in training and research. A contribution to the "functional histology" of the psychotherapy process]. AB - To be able to identify qualitative differences in the results of psychotherapeutic activity and to establish a relationship between those results and the particularities of the treatment process involved, the problems of the patient, the relevant events during therapy, and therapeutic results must be interrelatable both terminologically and theoretically (P-T-O congruence; Strupp et al., 1989). If, therefore, the relevant qualities of the relationships involved in interpersonal transactions during the therapeutic process are to be represented adequately and independently of schools, an appropriate instrument is required for both clinical and research use. This instrument is introduced here in the form of the Structural Analysis of Social Behavior (SASB) after Lorna Smith Benjamin by means of the key question: Who acts how toward whom and how does the latter react to this? PMID- 2238872 TI - [Social integration of Crohn disease and ulcerative colitis patients. Study of the relations of somatic, psychological and social factors]. AB - 63 patients with Crohn's disease and 58 patients with ulcerative colitis were tested with the "Fragebogen zur sozialen Integration" (FSI, questionnaire of social adjustment), the "Freiburger Personlichkeitsinventar" (FPI) and a semistandardized interview and were compared with surgical controls. Activity, course and symptoms of the disease were registered. We found significant restrictions in working and lesiure activities, partnership and sexual life in patients with inflammatory bowel disease. Social adjustment of patients with Crohn's disease was more dependent on disease activity than in patients with ulcerative colitis. Social impairment in patients with Crohn's disease correlated with higher stool frequency and abdominal pain, in patients with ulcerative colitis with reduced general state of health, tiredness and limpness. In the "Freiburger Personlichkeitsinventar" (FPI) the patients with chronic inflammatory bowel disease described themselves significantly more nervous, inhibited, reserved and less aggressive, sociable and composed. The FPI scores in patients with Crohn's disease depended more on disease activity and on somatic symptoms than in patients with ulcerative colitis. PMID- 2238873 TI - [Psychosomatic medicine for research and therapy in the field of human relations]. PMID- 2238874 TI - [Obstructive urine transport disorders of the upper urinary tract--pelvi-ureteral obstruction]. AB - In the present paper a review is given on etiology, pathology, morphology and pathophysiology of ureteropelvic junction obstruction. According to own experience and a literature review the current diagnostic and therapeutic procedure are evaluated with respect to their clinical relevance. PMID- 2238875 TI - [Electron microscopic study of calcium oxalate microcrystals]. AB - Morphology and size distribution of calcium oxalate microcrystals in the urine of healthy people and calcium oxalate stone formers are examined by scanning electron microscopy. The data are compared with coulter-counter investigation and the following clinically important result is discussed. This initial crystal population be composed of single crystals and in sick people larger crystals have been found. PMID- 2238876 TI - [Studies on the crystallization tendency of calcium oxalate in urine--a study of experimental and computer-assisted determination of the risk of urinary calculi formation]. AB - In this study a method o the semiquantitative determination of the crystallization tendency for calcium oxalate in urine is described. It is based on the addition of a well-defined amount of ammonium oxalate (31.3 nmol) to a urine sample (30 ml). The so caused clouding of the urine is measured by a photometer 20 min later. The method guarantees an acceptable reproducibility and is simple to be performed in each clinical laboratory. The results of mathematical correlation and discriminant analysis show that the calcium concentration influences the crystallization of calcium oxalate as most of all urinary constituents. Furthermore, evidence of a high specificity of the method is given by a reclassification rate of about 80% in the discriminant analytical computation. PMID- 2238877 TI - [Severe oligozoospermia as a sequela to partial obstruction of the seminiferous tubules]. AB - Arguments for the presence of a partial obstruction as cause of severe oligozoospermia may result from following findings. 1. The frequency of normal FSH values in oligozoospermia (44.9%) do not differ significantly from cases with azoospermia (50%). 2. Including a quantitative analysis of testicular morphology 5 out of 63 patients (7.9%) suffering from severe oligozoospermia show a normal spermatogenesis. 3. The frequency of this constellation in our material including severe oligozoospermia, normal testicular volume, normal FSH value, and normal spermatogenesis agree with few findings in the literature. The number of etiological factors of partial obstruction require also invasive diagnostical procedures like vas deferens radiography and surgical exploration. PMID- 2238878 TI - [Effects of chemotherapy and radiotherapy of malignant testicular tumors on residual testicular tissue]. AB - By morphologic and morphometric investigations of the residual testis after treatment of testicular cancer the deleterious effect of chemo- and radiotherapy are estimated. Approximately 4-5 years after treatment the reversibility of spermatogenesis is better in patients chemotherapy than in patients after radiotherapy. PMID- 2238879 TI - [Studies on the occurrence of texture types in calcium oxalate urinary stones]. AB - A review of texture types of calcium oxalate calculi and a pattern of 4 basic texture types was presented. A method of texture classification as a part of the routine polarization microscopy urinary calculus analysis was developed. Thereby a representative material could presented on the distribution of texture types. A connection between pathological urinary parameters and the texture type was demonstrated. PMID- 2238880 TI - [Urolithiasis in 2,8-dihydroxyadeninuria: presentation of 3 additional cases]. AB - To the now 17 case reports in caucasian patients of an urolithiasis in a rare purine metabolism disorder 2,8-dihydroxyadeninuria due to missing activity of adenine phosphoribosyltransferase 3 further cases are presented. Firstly, a monozygotic twin pair is afflicted (13-year-old boys). All calculi be composed of pure 2,8-DHA, except a mixed calculus in a 38-year-old man containing of 80% 2,8 DHA and 20% calcium oxalate. The actual literature is reviewed. PMID- 2238881 TI - [Simultaneous determination of the GRF and the ERPF (effective renal plasma flow) using a single blood sample in the slope clearance with 99mTc-DTPA and I 131 hippurate]. AB - In patients with various indications to renal split function diagnostics the plasma slope clearance of the Tc99m-DTPA and J131-Hippurate to the estimation of GFR and ERPF were performed with two or three blood samples in the monocompartment model (1 KM). In comparison these functional parameters were calculated on the basis of the only least blood sample (single-point procedure- EPV). The results of linear regression GFR (1 KM) = 12.7 + 0.978 * GFR (EPV), r = 0.986, N = 102 or ERPF (1 KM) = 22 + 1.13 * ERPF (EPV), r = 0.889, N = 68 may recommend the use as patient-safe procedure especially in poor venous access. Two short BASIC programs for estimation of GFR and ERPF are presented and the error ranges discussed. PMID- 2238882 TI - [Obstructive urine transport disorders of the upper urinary tract--pregnancy and iatrogenic lesions]. AB - The most important disturbances of pregnancy excluding the birth canal are complications due to diseases and alterations of the kidney and the urinary tract. The urinary transport disorders are of significant importance; frequency and clinical relevance and follow-up are presented. In the second part an overview to urinary tract disorders due to iatrogenic injuries is given. PMID- 2238883 TI - [Diagnosis and therapy of single kidney cysts]. AB - By means of observation of 191 own patients suffering from a symptomatic single renal cyst and a literature review, epidemiology, clinical presentation, diagnostic procedures and therapy are presented. The significance of ultrasonography and computerized tomography are emphasized. For single, symptom free cysts besides regular ultrasonographic examinations no further therapy is necessary. In case of a required therapeutic procedure, an open resection of the cyst should be preferred to percutaneous a required therapeutic procedure, an further therapy is necessary. In case of a required therapeutic procedure, an open resection of the cyst should be preferred percutaneous approach. PMID- 2238884 TI - [Factors influencing the result of kidney transplantation with special reference to the HLA system in conventional immunosuppression]. AB - Among 331 recipients of cadaveric renal allografts, transplanted from 1976 to 1986 at the Rostock Transplant Center the graft survival rates have been analyzed. All patients have been treated by conventional immunosuppressive therapy using azathioprine and prednisolone. A relation between graft survival and immunological factors was found: the better the HLA match, the better the transplant results. The necessity of a restrictive transfusion regime was stressed. The higher the number of pretransplant transfusions, the higher is the panel reactivity with following lower graft survival. Cold ischemic time was without influence on graft survival. The introduction of cyclosporin may improve the graft survival rate as known of 10-20%. PMID- 2238885 TI - [Precision of data from models of sodium kinetics in hemodialysis]. AB - The 1-pool-model of sodium kinetics during hemodialysis is based upon the assumption of an immediate compensation of osmotic shifts. This assumption is not supported by measurements of plasma sodium, total protein concentration and colloid osmotic pressure kinetics. When a high dialysate sodium concentration is applied, an inflow of sodium into the plasma space occurs, which results in an osmotic suction and thus a plasma dilution. These conditions can be represented by a 2-pool-model taking into consideration capillary filtration. The results indicate that following the first treatment period the sodium kinetics are sufficiently explained by a 1-pool-model with the total body water as distribution volume. Both the plasma sodium concentration and the eliminated sodium at the end of a hemodialysis treatment can be described to an acceptable level by the 1-pool-model. The input of the measured in-vivo sodium dialysance value (or alternatively the urea clearance) is necessary. PMID- 2238886 TI - [Measuring the thickness of the peritoneum as a dialysis membrane using various osmolar concentrations of dialysis fluid]. AB - Thickness measurements solutions on the rat peritoneum using peritoneum using peritoneal dialysis solutions of various osmolalities show a marked reduction of the distances between capillaries and peritoneal surface with increasing osmolality. This may caused by a dehydration of the peritoneum and support the so called canaliculus theory. If the dehydration of the peritoneum may outlast temporal the dialysis cycle with higher osmolar solution, it could be an explanation for the efficacy of following low-molecular solutions. PMID- 2238887 TI - Detection of circulating immune complexes in MRL mice with different forms of glomerulonephritis. AB - Serum levels of circulating immune complexes (CIC) in MRL mice were determined using the 125I-C1q binding test and a conglutinin enzyme assay. The serum 125I C1q and conglutinin binding capacity were correlated to the development of different forms of glomerulonephritis (GN) detected by light microscopy. The study was carried out with a total of 132 MRL/MpJ-lpr/lpr and MRL/MpJ(-)+/+ mice of different age groups. From the age of 3 months on an enormous elevation of C1q and conglutinin-binding CIC occurred in MRL/MpJ-lpr/lpr mice, while in MRL/MpJ( )+/+ mice the mean values of CIC remained low in all age groups studied. The results corresponded to histopathological glomerular findings. In lpr/lpr-mice, from the age of 3 months on, extremely severe proliferative forms of GN occurred. In most cases of +/+(-)mice examined comparatively mild glomerular lesions were found. In serum samples of Han:NMRI and C3H/He mice an increase of conglutinin binding material was found in certain age groups, while the levels of 125I-C1q binding activity remained low in mice of all age groups studied. PMID- 2238888 TI - [The sodium excretion behavior of anesthetized and conscious spontaneously hypertensive (SHR) and normotensive (WKY) rats]. AB - Urethane-anesthetized and conscious, immobilized SHR subjected to osmotic diuresis, responded to intravenous saline loading with a larger natriuresis than WKY-rats due to an increased urine sodium concentration without differences in urine flow. Blood pressure and heart rate reactions after saline loading were qualitatively different in anesthetized and conscious rats. The magnitude of these changes was larger in WKY than in SHR in both experimental groups. PMID- 2238889 TI - Effect of high sodium and high water intake on 24 h-potassium balance in dogs. AB - The influence of different amounts of oral sodium intake combined with high oral water intake on potassium excretion and plasma potassium concentration (PK) was evaluated. Female beagle dogs (11-16 kg) were divided into 2 groups: 1. Normal Sodium and high Water Intake (NSWI): 2.5 mmol Na, 3.55 mmol K, 91 ml H2O, and 277 kJ per kg body mass and 24 h (31 24 h-balance studies with 11 dogs). 2. High Sodium and high Water Intake (HSWI): Same diet as NSWI but 14.5 mmol Na x kg body mass-1 x 24 h-1 (55 24 h-balance studies with 21 dogs). The 24 h-balance studies were performed after different periods of time after onset of the respective diet (dogs in metabolic cages). Plasma sodium concentration (PNa) on NSWI was 148.4 +/ 2.6 mmol x 1(-1), whereas it was lower on HSWI (145.9 +/- 2.4 mmol x 1(-1). The lower plasma aldosterone concentration (PAC) on HSWI (24 +/- 8 pg x ml-1) compared to NSWI (67 +/- 38 pg x ml-1) may account for the lower PNa on HSWI. 24 h-sodium excretion was 93.6 +/- 6.5% of intake (%i) on HSWI and 91.5 +/- 20.7% i on NSWI. 24 h-water excretion was not different between both groups (81 +/- 7% i). PK was 3.93 +/- 0.25 mmol x 1(-1) on NSWI regardless of the time the dogs were on NSWI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2238891 TI - [Marburger prophylaxis model and its spread in the districts--report after 8 years]. PMID- 2238890 TI - Effects of age and body mass of recipients on survival of transferred embryos in mice. AB - To examine the effects of age and body mass of recipients on embryo survival during gestation, ICR embryos were transferred to nulli- or primi-parous females of 4 strains of mice. Out of 530 recipients, 383 (72.3%) produced a litter. Transfer of 3,465 embryos to 383 recipients resulted in production of 1,637 pups born alive, an overall rate of embryo survival of 47.2 +/- 1.1%. Regression analyses revealed that embryo survival decreased in older recipients and increased in heavier recipients. The results were consistent in each parity/strain group and all groups combined. PMID- 2238892 TI - [Toothpastes are more than polishing agents]. PMID- 2238893 TI - [War: the grim teacher of face surgery]. PMID- 2238894 TI - [Dental documentation with the office computer]. PMID- 2238895 TI - [Development of expert abilities in dental practice]. PMID- 2238896 TI - [Practice justified rubber dam technic]. PMID- 2238897 TI - [Much treatment in spite of dentists' own serious physical problems]. PMID- 2238898 TI - [Clinical matters of rhythm disturbances]. PMID- 2238899 TI - [Clinical, radiological and surgical therapeutic aspects. Mesiodens]. PMID- 2238900 TI - [Dentist of the future without helper?]. PMID- 2238901 TI - [Computer supported radiographic interpretation in everyday practice]. PMID- 2238902 TI - [RadioVisioGraphy: an innovation in dental radiography technic]. PMID- 2238903 TI - [Problems of epithetic concerns of facial defects]. PMID- 2238905 TI - [Non-precious alloy double crowns. Dental technic position]. PMID- 2238904 TI - [Real quality is only found after many years]. PMID- 2238907 TI - [EDP in dental office: present state of the art]. PMID- 2238906 TI - [Transcortical anchorage of subperiosteal splints: biomechanics and case report]. PMID- 2238908 TI - [Selection criteria of dental EDP-systems]. PMID- 2238910 TI - [Are confectioner's caries still an occupational disease?]. PMID- 2238909 TI - [EDP in dental practice. Future outlook]. PMID- 2238911 TI - [Dental importance of Morbus Bourneville-Pringle (tuberous sclerosis)]. PMID- 2238912 TI - [Pathophysiology of marginal periodontitis]. PMID- 2238913 TI - [T-scan--possibilities and limits of new occlusal diagnostic procedure]. PMID- 2238914 TI - [Intramuscular tongue lipoma]. PMID- 2238915 TI - [Dental group prophylaxis in kindergarten]. PMID- 2238916 TI - [Office hygiene: protection for patient and dental team]. PMID- 2238917 TI - [Esthetic posterior restoration--a field with limitless possibilities?]. PMID- 2238918 TI - [Materials in tooth retention: adhesive technics belong to the future!]. PMID- 2238919 TI - [Dental care in East Germany--an additional need]. PMID- 2238920 TI - [Investigation of preventive fissure sealing in caries prone dentition]. PMID- 2238921 TI - [History of calcium hydroxide in dentistry]. PMID- 2238922 TI - [Amalgam?]. PMID- 2238923 TI - [Caries prevention with fluoride--no risk for health]. PMID- 2238924 TI - [Intraligamentary anesthesia in dental practice: clinical study]. PMID- 2238925 TI - [Composite materials in posterior region: indications]. PMID- 2238927 TI - [Nutrition and nutritional guidance--treatment needs for dentists]. PMID- 2238926 TI - [State of dental implantation in Hungary]. PMID- 2238928 TI - [Prevention with fissure sealants]. PMID- 2238929 TI - [Activity of prevention aide in lower school]. PMID- 2238930 TI - [Oral hygiene--dental competence is questioned!]. PMID- 2238931 TI - [Complementary diagnostic and therapeutic methods]. PMID- 2238932 TI - [Radiographic diagnosis and clinical procedures with gutta percha points for root canal therapy]. PMID- 2238933 TI - [Possibilities for hypnosis in dental practice]. PMID- 2238934 TI - [Development of dental income]. PMID- 2238935 TI - [Safety measures in dental practice--what should be watched?]. PMID- 2238936 TI - [Quality and security of single use gloves]. PMID- 2238937 TI - [New possibilities of gingivitis and plaque prevention]. PMID- 2238938 TI - [Diffusion of chlorhexidine-C14 in dental enamel]. PMID- 2238939 TI - [Tooth abnormalities under different considerations of the distal end of dental arch]. PMID- 2238940 TI - [Occlusal surface structure in erosion using scanning electron microscopy]. PMID- 2238941 TI - [Posterior registration of articulated total prosthesis]. PMID- 2238942 TI - [Dental prophylaxis from peoples' point of view]. PMID- 2238944 TI - [Numerical steered finishing of prosthesis--start of a new era in dentistry?]. PMID- 2238943 TI - [Periodontology and function teaching]. PMID- 2238945 TI - [Changes in orthodontic findings in dyskinesia and dysgnathia after myofunctional therapy]. PMID- 2238946 TI - [Significance of ISO-Norm 6474 for aluminum oxide implants]. PMID- 2238947 TI - [Antimicrobial containing impression and model materials for infection prevention in the laboratory]. PMID- 2238948 TI - [Dental care in Norway]. PMID- 2238949 TI - [Aspects of use of new radiograph direct enlargement in dentistry]. PMID- 2238950 TI - [Occlusal surface modelling: individual buildup of finished pieces]. PMID- 2238951 TI - [Morita Panex-AC panoramic radiograph with autofocus system and automatic lighting]. PMID- 2238952 TI - [Pathologico-anatomic findings in spontaneous abortion and induced abortion during the 2nd pregnancy trimester]. AB - Reported in this paper are results obtained from morphological investigations of 200 fetal abortions which had occurred in the fourth to sixth months of pregnancy. They were spontaneous abortions and abortions induced primarily for fetal indications (31 cases). Causes are subdivided in this report by placental, fetal, and maternal factors. Fetal causes accounted for 18.5% of all cases (most of them fetal malformations, induced abortions included). Maternal causes accounted for 7.5%, among them edema-proteinuria-hypertension (EPH) gestosis and premature rupture of the amnion. No unambiguous clinical or morphological findings were established as causes in 36 cases, i.e. 18%. The majority of all causes, 55.5% was related to placental factors, among them impaired maturation of the placenta in 14.5%, disorders in maternal circulation in 17%, and inflammatory alterations in 23.5%. Early disorders in placentation accounted for a conspicuously high number of after-birth findings (complex early impairment of placental maturation in 28.6%), and so did maternal circulatory disorders, including retroplacental hemorrhage (55.2%), as well as decidual and membranous inflammations (43.4%). PMID- 2238953 TI - [Non-Hodgkin's lymphoma of the thyroid gland. Morphologic and immunohistochemical findings in 2 cases]. AB - Described in this paper are two cases of non-Hodgkin lymphoma (NHL) of the thyroid gland in women with Hashimoto's thyroiditis. NHL may be misinterpreted for its histological similarity to anaplastic thyroid carcinoma. The immunoperoxidase technique can be used with good success to confirm the lymphocytic origin of tumor cells. PMID- 2238954 TI - [Endophlebitis hepatica obliterans. Unusual cause of liver insufficiency in early childhood in a dizygotic twin]. AB - Findings recorded from obliterative hepatic endophlebitis are described in this paper and are compared with international literature. They had been obtained from a male twin who had died with clinical symptoms of hepatic failure. Differential diagnosis of liver insufficiency in early childhood is discussed in some detail. Also recorded was obliterative angiitis of intramural blood vessels in the ileum. Systemic vasculitis is postulated, possibly developed on the basis of an immunological reaction. Intra-uterine infection had probably been the most likely cause. PMID- 2238955 TI - [Tumor progression and metastasis]. AB - The heterogeneity of cells capable of metastasation has proved to be the greatest obstacle to successful treatment or to prevention of metastatic diseases. This variety appears to be attributable to processes of selection. Cytobiological investigations which are helpful in casting some light at selective mechanisms of metastasation may, perhaps, make substantive contributions to cancer therapy. PMID- 2238956 TI - [Effect of regional centralized treatment on chances of survival in rectal cancer in East Germany]. AB - Based on cases of rectum-carcinoma reported to the National Cancer Registry a population based method is demonstrated to measure the influence of a regional centralized treatment on the relative survival rates for cancer patients. This new approach use a centralization-index, characterizing the centralization of treatment activities in single countries. It is shown, that the end results in regions with a high index are much better than that in other regions. PMID- 2238957 TI - [The value of positron emission tomography in the diagnosis of recurrent rectal cancer]. AB - In 21 patients with clinically suspected recurrent rectal cancer showing a mass in the pelvic CT scan, Positron Emission Tomography (PET) was performed to measure metabolic rate of the mass. In 13 of the 21 patients an increased F-18 Fluorodeoxyglucose (FDG) uptake in the suspect tissue could be found. All of these patients were proven to suffer recurrent cancer by biopsy. 8 of the 21 patients showed normal uptake and 7 of them revealed scar tissue by histology. Therefore PET could distinguish clearly between cancer and scar tissue. PMID- 2238958 TI - [Surgical and oncologic principles of the removal of the rectum]. AB - Excision of the rectum should take in account that the main lymphatic spread follows the cranial route and that dissection of the rectal wall should be performed across its adjacent anatomical lamellae. It is not clear whether an extensive pelvic dissection and high ligature of the inferior mesenteric artery are beneficial. Spontaneous or iatrogenic perforation of the tumour considerable increases the incidence of local recurrence. The frequency of postoperative urinary and sexual dysfunction ranges from 3.5-57% and 14-38% respectively. The reported surgical mortality averages 5-6%. PMID- 2238959 TI - [Relevant "end points" for evaluation of the colon pouch after deep rectum resection]. AB - After low colo-rectal anastomosis there is in 25% a degree of urgency and increased bowel movements. In order to improve the reservoir continence the construction of a J-shaped colonic pouch seems reasonable. We have operated 5 patients with the new technique and worked up our preliminary results in connection with a literature overview. Increased bowel movements and urgency are reduced postoperatively but some patients report pouch evacuation problems, using enemas or suppositories to empty their reservoirs. To estimate the value of this new technique innovative endpoints as overall well-being and quality of life might be more important than conventional endpoints measuring only functional results. PMID- 2238960 TI - [Comment on the contribution: Pathogenesis of cancer in the operated stomach (St. Dittrich and G.-M. Fleischer)]. PMID- 2238962 TI - [When is there an indication for primary femoral amputation in patients with vascular disease?]. AB - Every patient suffering from arterial occlusive disease has to be considered a candidate for a bilateral amputation. Below-knee amputation is preferable if at all possible. Poor wound healing and reamputation at a higher level are factors to be expected in 20-30% of these patients. Therefore primary above-knee amputation is indicated only if a more distal amputation level is not possible, or if lower amputation offers no advantage to the patient. The question must be answered in each individual case. PMID- 2238961 TI - [Current status of amputation surgery]. AB - Limb salvage by revascularisation of occluded arterial pathways is main goal of vascular surgical activities. However, if dying or gangrenous tissue has to be removed, the question of: where to amputate--and the potential rehabilitation has to be answered. Septic amputation being an emergency operation has to be compared with elective one with definitive shaping of the stump. In major amputations knee disarticulation is preferred nowadays as being mostly "atraumatic" and well able for rehabilitation. In minor amputations bunions of the great and the little toes should be preserved especially in case the whole phalangeal and metatarsal forefoot amputation seems to have better results than removal of the first of fifth toe together with their metatarsia. A distal borderline amputation can only be performed in diabetics and after revascularisation of the feeding arterial tree. PMID- 2238963 TI - [Heart surgery interventions in risk patients. New possibilities for improving therapeutic results]. AB - Perioperative therapy in conjunction with cardiac surgery had so far been guided by functional, paraclinical, and clinical parameters which only conditionally enabled objective appraisal of the present condition of the myocardium. Perioperative recording of the arterio-coronary-venous concentration difference of lactate (acDL) has now enabled the use of an objectivated parameter for accurate description of the metabolic-energetic situation of the myocardium. This will be helpful in metabolic-energetic condition monitoring (MESM) to optimise perioperative cardiotonic therapy. Stabilisation of the metabolic-energetic situation of the myocardium, objectivated by MESM, has proved to be superior to premature cardiac support, using catecholamines. It has been associated with improved restitution with high significance (p less than 0.005). PMID- 2238964 TI - [Abdominal complications following heart surgery using the heart-lung machine]. AB - Reported in this paper are 17 abdominal complications among 2,161 patients, following cardiac surgery, using cardiopulmonary bypass. This incidence is comparatively low, accounting for only 0.78 percent, whereas figures between 0.3 and 1.6 percent have been reported in the international literature. Lethality worldwide has been quoted to be between 25 and 50 percent and amounted to 23.5 percent for the above patients. This seems to underscore the great importance of early decision-making on appropriate therapy. Haemorrhage from the upper gastro intestinal tract due to stress-related ulcers had been the predominant finding in this study. Acute pancreatitis developed in two patient, one of them ending in death. Acute cholecystitis and ischaemic colonic gangrene were additional complications. No significant extension of perfusion periods was established, which was in deviation from findings made by other authors. PMID- 2238965 TI - [Subcutaneous myxomas in atrial myxoma. A contribution to Swiss syndrome. A case report]. PMID- 2238966 TI - [A suture technique of transverse staged fixation plication following disobliteration of the carotid artery]. AB - A combination of carotid artery plication and fixing of the distal intima level is proposed in order to improve the surgical management during carotid endarterectomy. The own experience since 1987 (70 cases) shows this procedure to be recommendable especially for all cases with severe penetrating atherosclerosis. PMID- 2238967 TI - [Initial experiences in diagnosis of graft rejection following clinical heart transplantation. Detection of graft-directed activated T-cells]. AB - The binding of antigen-loaded carrier to mononuclear cells of heart transplant recipients has been investigated by means of an antigen-specific rosette technique. The increase of rosette forming cells and the inhibition of this reaction with monoclonal antibodies against activated T-cells is a sign of a beginning rejection. 3-6 days later infiltrating immunological competent cells are seen in biopsy. PMID- 2238968 TI - [Algorithm for diagnosis and prevention of postoperative deep vein thrombosis]. AB - An algorithm is described in this paper for diagnosis and prevention of postoperative deep venous thrombosis. It is presented in the form of a network graph and is based on an evaluation of the relative risk of pulmonary embolism of 17.785 patients. Age above 60 years, malignant disease, and more than four days of postoperative immobilisation were found to be the greatest risk factors for lethal embolism of the pulmonary artery. Examination of the venous flow bed by non-invasive methods has proved to be indicated for any patient who has not resumed spontaneous movement on the fourth postoperative day. Diagnostic coverage has so far been achieved for 75 per cent of all patients still immobilised four days after surgery. Peroral or rectal administration of aspirin (1.5 g:24 h-1) is recommended for its good therapeutic effectiveness to reduce complications and for economic reasons. PMID- 2238969 TI - [Our surgical heritage. On the development of abdominal surgery in the mirror of the controversy between Franz Kuhn and Hans Kehr]. PMID- 2238970 TI - [Life style and quality of life of children and adolescents following malignant tumor disease]. AB - Psychosocial support after the diagnosis of childhood cancer is absolutely necessary to help not only the patients but also the parents, family members, and friends to deal effectively with the emotion and social problems arising from the disease. Psychological support for the whole family, rooming-in facilities on the ward, parent-self-help-groups, social and financial helps reduce problems which flow from such a diagnosis and may develop a positive coping strategy. Experiences over a long period of psychosocial aftercare in the University Hospital of Heidelberg are analyzed and some scientific data of this model are reported. PMID- 2238971 TI - [Reconstructive surgery in tracheobronchial tumors]. AB - Malignant tumours are the most frequent indications for reconstructive tracheobronchial surgery. From 1970 to 15.6. 1989 there were 95 reconstructive operations on the tracheobronchial tree from this indication. Primary tumours of the trachea and the bifurcation are very rare, especially benign tumours. All tumours of the trachea and the bifurcation have need of a reconstruction, while this is an elective operation on the bronchial tree. The purpose of these operations is the preservation of lung tissue despite of radical resection. The main problem ist the insufficiency of the anastomosis (n = 6) associated with an acute pulmonary hemorrhage (n = 4) and death. The perioperative mortality was 9.5%. PMID- 2238972 TI - [Perioperative ultrasound examination of the breast in breast cancer]. AB - 127 cases of breast carcinoma were examined in a prospective study. By means of preoperative ultrasonography the staging following the pTNM-system validates the tumor size in 85.5% and the lymph node involvement in 77.2%. Multicentric multifocal carcinomas were diagnosed by ultrasonography in 20 of 29 cases, merely 9 of 29 by mammography. Ultrasonography of specimen is recommended in cases of negative clinical findings and positive ultrasound examination to verify tumour excision. In addition to clinical exploration and mammography the ultrasonography of the breast obtains a diagnostic significance for planning a conservative management of breast cancer. PMID- 2238973 TI - [Benign pulmonary coin lesions following multiple cancer surgeries]. PMID- 2238974 TI - [Tibial shaft fracture. Forms of therapy and their complications]. AB - The rate of complications in treatment of lower leg fractures has continued to be high, which calls for critical appraisal of possible therapeutic approaches. The effectiveness of both conservative and surgical treatment has been shown by a prospective study which covers a period from 1984 to 1988. An analysis of 166 cases proved helpful in providing guidelines for therapy of closed and open lower leg fractures. Conditions and prerequisites are expounded for the use of various surgical techniques, and hints are given on how to reduce complications. PMID- 2238975 TI - [Early complications and fatalities following surgical treatment of fractures of the upper ankle joint]. AB - In a retrospective study of 1,140 patients (1970-1988) with ankle joint fractures, treated according to the AO principles, we analyzed the surgical treatment. After surgical treatment of 501 patients the rate of early complications was 5% and the mortality 1%. In our opinion all fractures should be treated by the AO principles to ensure a good follow-up result. PMID- 2238977 TI - [Severe impalement injury with primary surgical, gynecologic and urologic management]. PMID- 2238976 TI - [External fixator in the district hospital]. AB - Follow-up checks were performed on 59 cases of external fixation between 1 and 9 years after operation. Complications are not severe, and all patients of this group finally had achieved a good or very good functional end result. External fixator is found a favourite method for use in an ordinary hospital as the author's. The criteria of indication particularly found a new evaluation. The need of giving the external fixator in accurately defined instability is emphasized. PMID- 2238978 TI - [Bone healing--an immunoreactive process?]. AB - Cell mediated immune reactions, demonstrated by leukocyte migration assay and histological analysis of spleen and lymph nodes, could be observed after fresh autografting of cortical segments in rats. The detected immune answer showed a bone-specific reaction pattern. In consideration of the temporal correlation of the observed immune reactions and the histological signs of graft incorporation, a connection of bone healing and immune system may be possible. PMID- 2238979 TI - [Functional therapy in treatment of fractures and joint injuries]. AB - Full and timely restoration of the function of an injured segment of the locomotor system is the treatment goal for all fractures and joint injuries. Functional aspects therefore have to be considered, when operative or conservative forms of treatment are chosen for a particular injury. We define a treatment as purely functional if the involved limb is either not immobilized at all or whenever the immobilization is incomplete and for a limited time only. At least partial function of the involved segment is therefore restored during the treatment. Purely functional treatment ist most applicable for stable fractures. Stable can be defined as the property of biological tissues to withstand physiological loads. Many joint injuries such as AC separation, ankle ligament rupture, Achilles tendon rupture, and isolated rupture of the medial collateral ligaments of the knee can also be treated functionally. PMID- 2238980 TI - [Which estrogens and gestagens should be prescribed after 45 years of age and for how long?]. PMID- 2238981 TI - [Effects of adjuvant chemotherapy of breast cancer on gonadal function]. AB - Premenopausal breast cancer patients frequently develop amenorrhea during adjuvant chemotherapy. Despite psychic distress and severe weight loss are possible causes for secondary amenorrhea in cancer patients, it is in this case due to the gonadotoxicity of the cytostatic drugs. Alkylating agents, such as cyclophosphamide, damage ovaries directly, resulting in ovarian fibrosis, atretic follicles and decline in estrogen production. Elevated plasma levels of LH and FSH show adequate reaction of the hypothalamohypophyseal unit. There is no change in the androgen production of stromal cells as well as in the plasma levels of prolactin and adrenal androgen precursors. Ovarian damage goes along with hot flushes, loss of libido and dyspareunia. The onset of amenorrhea is age- and dose related. Commonly the changes are irreversible. Estrogen replacement therapy promptly removes menopausal symptoms but is contra-indicated regarding the possible hormone-dependence of the tumor. In this case low dose medroxy progesterone acetate is indicated. PMID- 2238982 TI - [A modified Sarafoff suture for closure of the uterine wound in Cesarean section]. AB - Using a retrospective investigation the authors demonstrate the advantage of the modified Sarafoff-suture (a one layer suture of the myometrium) in comparison with the two-layer suture. The results shows a lower rate of febrile courses, less postoperative complications and a shorter hospital stay. The first clinical experiences showed less scar complications in the courses of vaginal delivery in patients with a previous caesarean section. Therefore, the authors advise the modified Sarafoff-suture for wound closure in caesarean section. PMID- 2238983 TI - [Development of partner relations and of the child after successful therapeutic donor insemination]. AB - The psychological development of couples and children was examined after successful therapeutic insemination by donor (TID). 222 couples were investigated by sending questionnaires to the families. 122 (55%) couples fulfilled our requests. The answers suggested that there was no deviation from the behaviour of the control groups concerning attitudes towards pregnancy and delivery, actual interrelation between wife and husband, degree of neurosis of the parents and children. The conclusion could be drawn that there was no need for more restriction on the TID provided that a good psychological diagnostic regarding the special TID-problems was performed before the insemination treatment. PMID- 2238984 TI - [Male subfertility and oral bacterial diseases]. AB - More than 70% of the husbands consulting the Dept. of Gynecology and Obstetrics of the RWTH Aachen for sterility since June 1987 needed treatment for bacteriospermia with germ concentrations greater than 10(4) cfu/ml ejaculate. In 23% of the treated men however, no convincing reduction of germ concentration were achieved. 36 patients with therapy-resistant bacteriospermia were sent to the Dept. of Dentistry of the RWTH Aachen. A lot of intra-oral foci were found, which got eliminated. Intra-operational bacterial specimens were taken and evaluated by a special diagnostic technique in the Dept. of Microbiology. It was shown that the bacterial spectrum of the intraoral specimens and the spermiograms were identical. Six months after completion of the dental therapy a new andrological examination was performed. Two thirds of the spermiograms now were already sterile. There was an improvement of the spermparameters as well as motility, morphology and density. It can be concluded from these results that there is a direct causal relationship between a symptomatic dental primary disease and bacteriospermia which probably leads to subfertility. PMID- 2238985 TI - [Complete closure or open healing of the skin of the vaginal stump in vaginal hysterectomy]. AB - This retrospective study covers a period of 10 years (1977-1986) during which a vaginal hysterectomy with or without colporrhaphy was carried out in 431 women. In 317 patients the skin at the end of the vaginal stump was closed primarily, whereas it was left open in 114 patients. Comparing both groups less morbidity-, secretion-, infection- and bleeding-rates can be found in the group with primary closure of the vaginal stump. The healing of the operative wound is much better when closed primarily. Fear of entrapped secretions or formation of abscess or hematoma is not justified. PMID- 2238987 TI - [Treatment of primary dysmenorrhea with Jenapharm piroxicam]. AB - 36 patients with 432 menstrual cycles and primary dysmenorrhea were treated with Piroxicam-Jenapharm. Piroxicam-Jenapharm was given in a dose of 40 mg once daily for the first 2 days followed by 20 mg once daily. Piroxicam, a nonsteroidal-anti inflammatory drug (NSAID) is an effective drug in reducing menstrual pain intensity in 80%. Piroxicam was well tolerated with no patient reporting side effects. The treatment of primary dysmenorrhea with total 100 mg Piroxicam Jenapharm over 3 days is recommended. PMID- 2238986 TI - [Computer-assisted analysis of the tocogram. Initial experience using a new evaluation procedure]. AB - This paper describes first observations with a new computer aided analysis of tocogram. It seems that length of uterine contraction is an important parameter for quality of labour. In 9 from 12 cases promotion to constant length of labour with relatively low absolute duration of contractions was connected with a distinct increase of the velocity of cervical dilatation. The uniformity can be an important factor for the conversion into active phase of labour. PMID- 2238988 TI - [Differential diagnosis of pelvic tumors. Abscess forming ileovesical fistula in Crohn's disease. A case report]. AB - A report is given about a case of preoperatively unrecognized ileovesical-fistula caused by Crohn's-disease. Despite of uncharacteristic symptoms a more extensive medical history might have brought to also more extensive diagnostic methods and to suspicion of the intestinal disease. PMID- 2238989 TI - [New pregnancy following previous HELLP syndrome. A case report]. AB - The HELLP-Syndrome (H = hemolysis, EL = elevated liver enzymes, LP = low platelets) is a well known and severe form of gestosis. In this case report we analyse the positive outcome of a pregnancy after HELLP-Syndrome has happened. The obstetric management requires regular control of the complete blood count, SMAC and coagulation. PMID- 2238990 TI - [Aspiration of a gestational sac controlled by vaginal ultrasound in multiple pregnancy for the purpose of selective abortion]. AB - A case of an infertile married couple by whom the cause of infertility was oligoasthenospermia of man is described. The couple was treated by intrauterine insemination by capacitated spermatozoa in a cycle stimulated by clomiphene. The ultrasonography revealed a pregnancy of triplets. The patient refused a multiple pregnancy and asked for its interruption. As an alternative we proposed the selective abortion by means of an ultrasound-guided aspiration of two gestational sacs. Description of this method and the result are the theme of our paper. PMID- 2238991 TI - [Is in hypertension in labor, for example in EPH gestosis, active control of the placental period defensible?]. PMID- 2238992 TI - [Screening for toxoplasmosis and rubella in prenatal care?]. PMID- 2238994 TI - [Bacteriuria screening in gynecologic practice: what is the value of mid-stream urine?]. AB - In 55 healthy women corresponding urine proofs were taken by suprapubic punction and by mid stream technique from the same content of the urinary bladder. For detection or exclusion of bacteriuria both collection-methods are of equal value. In 96% of the cases the microbiological results were corresponding. The leucocyte count is of no value to detect indirectly a bacteriuria as well in punction- and in mid stream urine. A pathologic count is just as little pathognomonic for infection as a normal count excludes a bacteriuria. Therefore the counting of leucocytes should be given up to the favour of a better microbiological observation in gynecological outpatient departments. PMID- 2238993 TI - [Lesion of the ureteral wall caused by gynecologic surgeries from the urologic viewpoint]. AB - It is reported on 31 ureteral strictures in 29 female patients after abdominal or vaginal, simple or complex hysterectomy. In 21 cases the ureteral obstruction was combined with an external urinary fistula. In 11 cases it was noted a spontaneous receding of the ureteral obstruction respectively a sanitation of the urinary fistula without stenosis. The general renal protection in form of a nephrostomy as an important component of therapy is recommended. Directions for the medical care of intraoperatively diagnosed ureteral lesions are given. PMID- 2238995 TI - [Diagnosis of urinary tract infections in puerperium]. AB - In 225 puerperant urine proofs were taken both by suprapubic puncture and by mid stream technique. The corresponding proofs were examined culturally and microscopically. 42% of the mid stream proofs containing more than 10(5) germs/ml were evaluated to be false-positive. The corresponding urine taken by suprapubic puncture was uninfected. A pathologic leucocyte-count is just a little representative for urinary tract infection as a normal leucocyte count excludes an infection. Therefore, the counting of leucocytes is worthless and should be given up to the favour of bacteriologic examinations. Every ward for puerperant should presuppose the technique to take urine proofs by suprapubic puncture. PMID- 2238996 TI - [Urogynecologic follow-up examinations after radiotherapy of gynecologic malignancies]. AB - 47 women treated by radiotherapy for gynecologic malignancies have been examined urogynecologically. There are only some changes of subjective cystometric parameters (volume of the first desire to void, bladder capacity), but statistical significant changes of the parameters "compliance" and "bladder pressure at capacity". The parameters of urethrocystometry and uroflowmetry are not influenced by irradiation. The urethroscopy demonstrates a white mucosa of the bladder wall caused by irradiation fibrosis, agreeing to data reported by literature. Only 10 of the 47 patients examined had to be treated by drugs. PMID- 2238997 TI - [Delayed hypersensitivity to Candida albicans]. AB - Conditions and factors influencing the formation of delayed hypersensitivity (DH) to yeast-like fungi of the species C. albicans under experimental conditions have been studied. The intensity of this reaction has been found to depend on the dose and method used for infecting mice, the time of the test and the qualitative state of fungal cells. As the result of this study, the infectious model of DH to C. albicans has been proposed. This model may be used for the study of the influence of different exogenous and endogenous factors of cell-mediated immune response to candidiasis. PMID- 2238998 TI - [An evaluation of the extent to which young people are informed about the acquired immunodeficiency syndrome]. AB - The data on the evaluation of the volume of information on the transmission routes of HIV infection, risk groups and prophylactic measures, acquired by young people aged 14-18 years, their attitude to different sources of information on AIDS, as well as the evaluation of the influence of lectures on the formation of their opinion of these problems, are presented. As found by questioning, 84.4 98.7% of adolescents who answered the questionnaires correctly indicated the routes of the transmission of HIV infection, prophylactic measures were known to 73.1-90.3%, risk groups were correctly defined by 80.6-98.0%, more than 70% of adolescents covered by questioning believed that mass media provided insufficient information on AIDS. In a group of adolescents given a lecture an increase in the number of correct answers and a decrease in the number of wrong answers on the transmission routes of HIV infection and on risk groups were registered. PMID- 2238999 TI - [The anti-infection resistance system and the pathogenesis of bacterial endocarditis in patients with congenital heart defects]. AB - The clinico-immuno-microbiological study of 24 patients with congenital heart diseases was made. Clinically, the patients were subdivided into two groups: 8 patients with diagnosed bacterial endocarditis (BE) prior to the operation and 16 patients without BE. The analysis of the results of investigation carried out prior to the operation showed that age, the form of the disease and its duration did not affect the level of anti-infectious resistance factors (AIRF): in both groups a decrease in the level of AIRF characteristics (cell-mediated and humoral) was noted and no characteristic differences were determined. The results of the study of microflora from the nasal and laryngeal mucosa showed no difference in both groups of the patients. At the same time the detailed analysis of the results made it possible to suggest that BE caused by Streptococcus epidermidis and Streptococcus aureus inhabiting the mucous membrane of the anterior sections of the nasal cavity, alpha-hemolytic streptococci and S. epidermidis inhibiting the laryngeal mucosa. The results of the analysis made 3-6 months after the operation were also indicative of the absence of essential differences between AIRF characteristics observed in patients with confirmed and clinically unconfirmed BE. The clinical manifestation of this fact was an increase in the percentage of diagnosed BE cases up to 70% as compared with that before the operation (33%). This clinico-immuno-microbiological study made it possible to come to the conclusion that any form of congenital heart disease develops in combination with BE and/or is its prodrome. PMID- 2239000 TI - [The antimicrobial action of the xanthine oxidase-xanthine system on the causative agent of cholera]. AB - As revealed in experiments on V. cholerae, the enzymatic link xanthine oxidase xanthine produces a vibriostatic effect at the concentration of xanthine oxidase equal to 0.0125 g/l and a vibriocidal effect at the concentration of xanthine oxidase equal to 0.025 g/l in a medium with pH 7.5-7.6. In the presence of protein the antivibrionic activity of the xanthine oxidase link is decreased. The introduction of bivalent iron into the enzymatic link xanthine oxidase-xanthine enhances its vibriocidal action on V. cholerae. PMID- 2239001 TI - [The immune status of children in foci of measles infection studied by an immunoenzyme method]. AB - Children immunized with live measles vaccine in the foci of measles infection varying in intensity (1-9 cases per focus) have been subjected by two methods: the hemagglutination inhibition (HAI) test and the enzyme immunoassay (EIA). As shown in this study, in most cases (98% of all blood serum samples) the correlation between the results of the HAI test and EIA is not high (r = 0.5), which is linked with the detection of a wider spectrum of antibodies in EIA. The percentage of seronegative children detected by these two methods was practically the same (4.05 and 4.4, respectively). The analysis of the results obtained in this study indicates that EIA is a more informative and sensitive method, which confirms the effectiveness of its use for the determination of the level of collective immunity. PMID- 2239003 TI - [The results of an immunoepidemiological examination of foci of epidemic parotitis]. AB - The immunoepidemiological survey of 54 foci of epidemic parotitis showed that the epidemiological effectiveness index at preschool institutions, equal to 2.7, was essentially higher than at schools (2.1). The significant difference (t = 3.35) in the epidemiological effectiveness indices was due to the presence of a large number of persons having had inapparent and faintly pronounced forms of epidemic parotitis among school children, as well as due to more close contacts of children with the foci of infection at preschool institutions. The study showed that among children immunized with some lots of parotitis vaccine elevated morbidity in epidemic parotitis was registered. In the foci of infection children, immunized in the presence of low initial titers of specific hemagglutinins in their sera, responded by a booster effect with different duration of stimulation of antibody formation. The hemagglutinin titer of 1:20 was shown to protect children from epidemic parotitis. PMID- 2239002 TI - [The meadow-field type of tularemia foci in eastern Siberia]. AB - The article characterizes a meadow-type focus tularemia, discovered in Zalarinski'i District of Irkutsk Province in 1988. This focus and another similar focus discovered in 1985 at the Krasnoyarsk Territory belong to the meadow type, which makes it possible to regard their presence in Eastern Siberia as an established fact. The main reservoirs and sources of infection in these foci are two species of voles (Microtus gregalis and M. subarvalis). PMID- 2239004 TI - [The clinico-epidemiological characteristics of the course and diagnosis of tick borne rickettsiosis in northern Asia]. AB - The study of tick-borne rickettsiosis in Northern Asia has made it possible to determine the clinico-epidemiological features of the modern course of this disease, which should be taken into consideration for the timely diagnosis of this infection. The laboratory verification of the diagnosis should be carried out, as recommended by the authors, in the agar precipitation and leukocytosis tests in their modification. PMID- 2239005 TI - [The enterotoxigenic capacity of hemolysin-producing strains of Proteus isolated in acute intestinal infections in children]. AB - The capacity of P. mirabilis and P. vulgaris strains isolated in acute enteric infections in children for producing enterohemolysin, a new type of hemolysin, has been shown. The relationship between the capacity of Proteus cultures for producing enterohemolysin and their capacity for inducing toxic secretory reaction on a ligated loop on the small intestine of rabbits in the absence of known thermostable and thermolabile antitoxin in bacteria. PMID- 2239006 TI - [Infectious disease mortality in the USSR]. AB - In recent decades infectious and parasitic diseases (class 1 according to the International Classification of Diseases-9) constitute 2-3% of causes in the total morbidity structures in the USSR. The main causes of death among diseases of class 1 are tuberculosis (37%), acute enteric infections (30%), septicemia (11%), viral hepatitides (11%), meningococcal infection (4%), measles (2%). The main groups are children aged up to 2 years (48% of fatal cases of diseases belonging to class 1). The territorial irregularity of mortality indices has been revealed. PMID- 2239007 TI - [The results of multiyear observations on the duration of the maintenance of immunity in those vaccinated and revaccinated against and recovered from measles]. AB - The results of 5-year observations on the duration of immunity to measles virus in persons vaccinated and revaccinated against measles, as well as in persons having had this infection, are presented. The intensity of immunity was determined in the same persons with the use of the passive hemagglutination test. The study revealed differences in the formation, intensity and duration of postvaccinal immunity. A significant decrease in the concentration of antibodies over the period of 5 years was established in 50.0-52.3% of vaccines. Revaccination with live measles vaccine is an effective measure for enhancing immunity to measles virus in persons with initial antibody titers less than 1:10 1:20, but revaccination made in a single injection is not sufficient for the stable maintenance of measles morbidity at the sporadic level. Postinfectious immunity is characterized by stability and has no tendency towards decrease. Persons having had measles have no need in additional measures irrespective of the time elapsed after the disease. PMID- 2239008 TI - [The rapid diagnosis of measles by using immunoenzyme analysis based on peroxidase-labelled viral antigens]. AB - The sensitivity and specificity of the enzyme immunoassay (the capture variant), based on the use of the complex of anti-IgM-IgM to purified measles virus, the peroxidase-labeled lysate and nucleocapsid antigens of measles virus, were evaluated. The advantages of the nucleocapsid conjugate were established. The study of 200 serum samples from measles patients revealed that antimeasles IgM antibodies could be detected in 100% of cases, and the assay of 15 serum samples from healthy donors and 5 serum samples from patients with autoimmune diseases did not yield a single false positive result. PMID- 2239009 TI - [The indices of antipneumococcal immunity in children with chronic pneumonia]. AB - In 76 children with chronic pneumonia the levels of serum antibodies to pneumococcal capsular polysaccharide antigens (serotypes 1, 3, 6B, 8, 9N, 15F, 23F), O-polysaccharide and pneumococcal protein somatic antigens were determined by ELISA techniques. The study showed that in sick children the content of antipneumococcal antibodies in the blood increased with age. No correlation between the content of total immunoglobulins and that of antipneumococcal antibodies in the blood of the patients was established, but a sharp decrease in the concentration of antibodies was registered in a child with hypoglobulinemia. No increase in the level of antibodies to pneumococcal antigens was observed in cases of the exacerbation of Pneumococcus-induced inflammatory process in the lungs. PMID- 2239010 TI - [The protection of vertebrate animals from experimental tick-borne encephalitis with active and passive immunization against tick antigens]. AB - The active and passive immunization of laboratory animals against Ixodes antigens has been experimentally shown to lead to the development of their resistance to homologous Arthropoda species and a change in the intensity of the circulation of tick-borne encephalitis virus between carriers and their hosts. The immunization of vertebrates with Ixodes antigens may supposedly lead to a decrease in the number of bloodsucking arthropods-carriers of the causative agents of infectious diseases-and protect animals from infections whose causative agents are transmitted by Ixodes ticks. PMID- 2239011 TI - [Chemonucleolysis: the last step in the conservative treatment of lumbar herniated disk]. PMID- 2239013 TI - [Respiratory physiotherapy in lung diseases]. PMID- 2239012 TI - [Peripheral facial paralysis. Experience of a multidisciplinary approach]. AB - The authors report the evolution of 54 patients suffering from complete paralysis of the seventh cranial nerve. They point out the interest of a good diagnose and a multidisciplinary treatment including: drugs, infiltration, kinesitherapy and electrotherapy. A good repair (77%) is obtained if the treatment is early and regular. This therapy will be used according the results of clinical and electrophysiological examinations. PMID- 2239014 TI - [Congenital malformations at the level of the upper extremities: Poland syndrome]. AB - The authors describe the different congenital anomalies of the upper extremity. Starting from a case, thereafter they give a precise description of the Poland syndrome. PMID- 2239015 TI - [Respiratory problems and rehabilitation in medullary lesions]. PMID- 2239016 TI - [Peri-articular ossifications]. AB - Restriction of motion of the joints due to peri-articular ossifications constitute a major problem in the rehabilitation of patients with transverse spinal cord lesion. The therapeutic possibilities as well as the preventive measurements are described and illustrated with a few case reports. PMID- 2239017 TI - A retrospective study of the conservative treatment of tennis-elbow. AB - The files of 64 patients (70 tennis elbows) treated in our department because of tennis elbow complaints, were reviewed. The results showed injection with a corticosteroid preparation to be effective in alleviating the pain in the short term (91% improvement within 1 week), but the incidence of recurrence of symptoms to be high (51%) after an average period of 3 months). Physical therapy appeared to be less effective (47% improvement after an average of 6 weeks or 20 sessions), but recurrence of symptoms was far less frequent (5%). PMID- 2239018 TI - [EMG study of the external anal sphincter: current diagnostic aids]. PMID- 2239019 TI - Effect of small bowel resection on fecal bile acid excretion and on experimental colon tumour in rats. AB - Ileal and jejunal resections were carried out to investigate their effect on the faecal bile acid excretion and on the development of 1,2-dimethylhydrazine (DMH) induced colonic cancer in rats. Both resection types raise the total daily faecal bile acid level compared to the control sham-operated group, whereas ileal resection has a more pronounced effect. The incidence of tumours was found higher in groups with enhanced faecal bile acid level. Our findings show a connection between the daily faecal bile acid excretion and the incidence of DMH-induced colonic cancer. PMID- 2239021 TI - Factors affecting the cold transfer during cryotherapy. AB - Cryotherapy of the cervix was made in 40 patients for chronic cervicitis, and the thickness of the ice zone around the probe was measured in function of treatment time, under standard cooling conditions. The pace of growth of the ice zone allowed the author to draw conclusions as to the conductivity of the studied tissue. It was established that in the study-group, the patient's age and their histories of abortions did not influence the cold transfer significantly. The difference between the average values of ice zone thickness measured in the groups of nulliparae and multiparae was, however, significant. Findings have shown that the spread of cold in the cervical tissue in nulliparous women is better than in multiparae and so a greater efficacy of cryotherapy can be expected in nulliparae. PMID- 2239020 TI - The modern approach of hangman's fracture. AB - Upper cervical spine injuries associated with the characteristic alterations of the axis are termed by the international literature as hangman's fracture (HF). The specific changes of the clinical picture include fracture of the bilateral pedicles of the axis, dislocation of the arch, luxation and discopathy between the second and third (C2-C3) vertebrae, eventually other accessory fractures of vertebrae C2-C3 (Fig. 1). There are two kinds of it, i.e. (i) one of a hyperextensive-distractive mechanism with the very severe neurological lesion leading to the classical injury due to hanging and (ii) one of a hyperextensive compressive mechanism without neurological lesion of current traffic injuries or with slight neurological symptoms. The latter more often occurring type of injury encompasses a relatively wide range, which can be classified into three types: The stable injuries can be managed by conservative treatment, the unstable ones by Halo treatment or ventral surgical therapy meeting the up-to-date requirements. Prognosis is good. The authors have been the first in Hungary to present a critical and detailed survey of the world literature and their 11-year experience, in the form of a clinical study. PMID- 2239022 TI - Invasive intrauterine procedures in twin pregnancies discordant for fetal malformation. AB - Invasive intrauterine procedures in two twin pregnancies for exencephaly and multiple malformations are reported. In the first case, to ensure the development of the normal fetus, selective feticide of the affected fetus was undertaken by transabdominal intracardial injection of 20% NaCl solution. A healthy newborn infant with normal weight and a fetus papyraceus were delivered at term. In the second case, because of monoamnial placentation, the procedure was regarded too dangerous, therefore, only therapeutic amniocentesis was carried out to decrease the volume of amniotic fluid. The fetuses were delivered in the preterm period. The advantages of the procedure of selective feticide developed by the authors are also discussed. PMID- 2239023 TI - Fentanyl-midazolam-flumazenil anaesthesia during induced abortion. AB - A new anaesthetic method (fentanyl-midazolam-flumazenil) was compared with recently administered (pethidine-diazepam-ketamine) anaesthesia in two groups of 25 women, each undergoing termination of pregnancy. No significant difference was found between the two groups in the quality of anaesthesia. Recovery was assessed by means of the Aldrete score and a visual analogue scale. The recovery time was significantly shorter in patients who received midazolam-flumazenil. In the ketamine group, 36% of the patients complained of unpleasant dreams. The recovery in the midazolam group was comfortable. PMID- 2239024 TI - Measuring blood loss during transurethral resections. AB - Blood loss was measured in 70 patients during the transurethral resection for bladder neck adenoma and prostatic tumour on the basis of the haemoglobin content of the irrigation fluid, and the factors influencing blood loss were assessed. In 20 patients an irrigation fluid of body temperature was used. Their investigations have not proved the irrigation fluid of a higher temperature to be of a bleeding-inducing effect. It was stated that the absolute amount of bleeding was directly proportional to the weight of the resected tissue and the time of resection. These data revealed that a blood loss/1g of resected material/1 min of resection time does not increase with a larger resection weight or during a longer operation. PMID- 2239025 TI - Vitamin B12 absorption in some selected pathological states of the gastrointestinal tract. AB - The absorption of vitamin B12 in selected pathological states of the gastrointestinal tract was studied. Schilling test was performed with 37 kBq (1 microCi) of 57Co-labelled vitamin B12 as an analysis of urinary radioactivity. No increase in cobalamin absorption was present after exogenous IF had been administrated to patients after resection of the upper part the stomach and total gastrectomy. This suggests that there is another factor likely to affect vitamin B12 absorption. PMID- 2239026 TI - Data on the pathophysiology and clinical aspects of the mechanical obstruction of the small intestine. AB - A brief overview is given of the relevant physiology of the small intestine, and the pathomechanism of the clinical picture, based on a material of 423 patients with mechanical obstruction of the small intestine. The various forms of the mechanical obstruction of the small intestine are reviewed, with special regard to strangulation and adhesive obstruction. The possible forms of treatment are dealt with, with an emphasis on the importance of an early surgical intervention and of a careful after-treatment with a view to reducing the still high morbidity rate. PMID- 2239027 TI - Long-term feeding of casein or soy protein with or without cholesterol in Mongolian gerbils. I. Morphologic effects. AB - This study was designed to determine whether male Mongolian gerbils (Meriones unguiculatus) develop atherosclerosis (AS) during long-term feeding of diets similar to those consumed by humans. Gerbils were fed diets containing 16% casein (C) or soy (S) protein +/- 0.1% cholesterol (CH) for 15 months. The energy contribution from protein, fat and carbohydrate was similar to the energy distribution reported for the average North American (NA) diet and the level of added dietary CH resembled the average NA intake. At mo 0, 3, 6, 9, 12 and 15, animals were killed and tissue sections were prepared for histologic examination. Microscopic observations of cardiovascular tissues did not reveal any evidence of AS in any of the diet groups. Liver fatty infiltration (FI) was evident in the C+CH and C groups at mo 3 and 9, respectively, and continued to occur at all subsequent sampling times. Livers from gerbils fed S+CH also began to exhibit FI at mo 9, while livers from S-fed gerbils did not show any significant morphologic changes. Biochemical liver total lipid results supported the histological liver findings. Other tissues examined did not reveal any morphological changes related to diet. The gerbil may be a useful animal model to study mechanisms which inhibit AS development. PMID- 2239028 TI - Long-term feeding of casein or soy protein with or without cholesterol in Mongolian gerbils. II. Plasma lipid and liver cholesterol responses. AB - Male Mongolian gerbils (Meriones unguiculatus) were fed casein or soy protein in the presence and absence of dietary cholesterol for 15 months. Diets resembled the average North American diet in energy contributions from protein, fat and carbohydrate, cholesterol content and fatty acid profile. At month 0, 3, 6, 9, 12 and 15, plasma samples were analyzed for total cholesterol (TC), HDL cholesterol (HDLC) and triglyceride (TG) concentrations. Plasma LDL cholesterol (LDLC) was estimated indirectly. Liver TC was also determined at these time points. Comparisons of protein source and cholesterol level were averaged over the 15 month period. Casein-fed gerbils had significantly higher plasma TC and TG levels and lower HDLC levels (as a percent of TC) compared to soy-fed animals, independent of the presence or absence of dietary cholesterol. LDLC was significantly elevated in casein-fed gerbils only when cholesterol was present in the diet. Elevations in plasma TC levels were reflected by elevations in liver TC. Despite plasma lipid elevations that are consistent with the development of atherosclerosis (AS) and coronary heart disease (CHD) in humans, hyperlipidemic gerbils do not develop AS. Further characterization of gerbil lipid metabolism responses to dietary alterations aimed at the prevention of CHD in humans is necessary to elucidate the mechanism for the gerbil's resistance to AS. PMID- 2239029 TI - Serum calcium and blood pressure in Greek girls. AB - In a random sample of 492 girls 12-15-years-old total serum calcium appeared to be correlated with blood pressure. Adolescents with total serum calcium equal to a greater than the cohort mean (2.5 mmol/l) had higher systolic blood pressures than those with a value below the cohort mean. This was present at all ages. PMID- 2239030 TI - Changes in dietary habits, cardiovascular risk factors and mortality in Japan. PMID- 2239031 TI - Legionellosis and "torsades de pointes". AB - Myocarditis, pericarditis and endocarditis are rare manifestations of Legionella pneumophila infection. We describe a case of myocarditis complicated with a potentially fatal arrhythmia: "torsades de pointes". PMID- 2239032 TI - [Renal autotransplantation]. AB - The progress of renal transplantation in the last 2 decades has made possible the development of autotransplantation and extracorporeal surgery of the kidney. By those techniques, it is possible to operate upon patients in which conservative conventional surgery is impossible. In this article the technique is described, and two typical cases are reported. The mean indications are renal vascular hypertension, malignant tumors of the kidney, traumatic lesions of the kidney and ureteral lesions. All these indications are described in detail. PMID- 2239033 TI - [The treatment of perforated gastro-duodenal ulcer]. AB - Seventy-four patients, admitted in emergency for acute perforation of a duodenal or gastric ulcer were reviewed retrospectively: 40 patients with one or several risk factor such as shock, old perforation, severe chronic illness or advanced age and 34 other patients without any risk factor. In this selected population, the surgical treatment, initially performed in 44 cases, consisted of suturing the perforation and draining the peritoneal cavity in all cases but four in which it was associated with a vagotomy (2 cases) or a distal gastrectomy (2 cases). Thirty younger patients admitted without shock, within 6 hours following the onset of the perforation were initially treated by digestive aspiration alone: this medical treatment was successful in 15 patients but required a subsequent laparotomy in the other cases. The overall postoperative mortality is 18% but is zero in the group of patients in whom a medical therapy was initially performed. Long-term follow-up shows that 70% of the patients with a perforated duodenal ulcer and without any anti-inflammatory drug past history at the time of the perforation are free from any symptom. A strategy for the management of perforated duodenal and gastric ulcers, applicable to a non-selected population, is proposed in reference to the surgical literature. PMID- 2239034 TI - [Gastric metastases of ovarian adenocarcinoma. Apropos of a case]. AB - A case report and review of literature. Four types of neoplastic dissemination exist in presence of ovarian adenocarcinomas. Commonly, these tumors metastasize along intraperitoneal ways or lymphatic channels. Less frequently, the tumors are invading surrounding organs by direct extension. Rarely, there is a hematogenous dissemination. The observation of a gastric metastasis is reported; we consider it as a hematogenous one. Reviewing the literature, we find few similar cases. Gastric metastases originate more frequently from malignant melanomas, adenocarcinomas of the breast and bronchogenic tumors. PMID- 2239035 TI - [Giant chondrosarcoma: a case report]. AB - Chondrosarcoma is a slow-growing malignant tumor, with a mainly local infiltration, usually arising from skeletal cartilaginous cells. However, a few such neoplasms also arise from extraskeletal mesenchymal cells. Metastasis are usually seen with undifferentiated tumors (grade III), mainly within the lungs. The best treatment associates total surgical resection with chemotherapy. Radiotherapy is of poor use. Isolated pulmonary metastasis can be profitably withdrawn. Prognosis is about of 75% of survival after 10 years, in case of well differentiated tumors (grade I). The prognosis is far worse for undifferentiated tumors (grade III), turning around 10% of survival after 10 years. PMID- 2239036 TI - [Orthopedic treatment of the child with multiple injuries and its current progress]. AB - We regularly use the Elastic Stable Intramedullary Nailing (ESIN) for children over seven years old with shaft limb fractures. This technique is especially adapted to pediatric traumatology, and is to be preferred to rigid osteosynthesis or osteotaxis in closed fractures. We use ESIN as a rule for femoral shaft fractures. Unstable fractures of shaft forearm, tibia and humerus are treated following this technique, as for multiple fractures of the lower limbs. Because of immediate and complete fracture stability. ESIN is especially useful in multiple trauma patients, where nursing facilities and easy transport are helpful. Moreover, re-education can be performed immediately, with a very early walk recovery. PMID- 2239037 TI - [Simultaneous coronary and carotid surgery: apropos of 73 cases]. AB - A series of 73 simultaneous carotid and coronary revascularizations (Group I) is presented (January 1980-December 1988). Age, sex, risk factors, severity of angina, coronarography, neurological symptoms, angiographic carotid lesions and operative outcome of these 73 patients are compared with the aspects of 3544 coronary bypass patients (Group II) and 1001 carotid endarterectomized patients (Group III) during the same period. The angina in Group I is more severe, with 22% belonging to NYHA class IV and 26% having a stenosis of the left main coronary artery, vs 14% and 13% in Group II. Seventy percent of the carotid lesions in Group I are asymptomatic vs 33% in Group III. Group I patients had more problems in the perioperative period, with 16.4% needing prolonged high doses analeptics and 5.4% intraaortic counterpulsation balloon. Operative mortality is higher (7%) in Group I compared with Group II (2.3%) and Group III (1.7%). These results permit to define a population of polyvascular patients with concomitant coronary and carotid disease, characterized by a more diffuse atherosclerosis and a higher operative risk. Operative morbidity and mortality after combined myocardial and cerebral revascularization remains nevertheless inferior to the cumulated surgical risk of the sequential procedures (74 patients with coexistant coronary and carotid lesions operated in two sessions before 1986). PMID- 2239038 TI - Combined one stage cardiac and pulmonary surgery by median sternotomy. AB - From 1985 to 1989, 6 patients underwent a pulmonary surgical procedure simultaneously with a cardiac operation. All patients were male with a mean age of 60 +/- 8 years. The cardiac procedures included: 1 aortic and 1 mitral valve replacement, 3 coronary artery bypass grafts and 1 closure of an atrial septal defect. Four patients had primary pulmonary nodules: 2 bronchogenic carcinomas and 2 benign hamartomas. They presented with cardiac symptoms, and lung nodules were incidentally found on preoperative Chest X-Rays. The 2 last patients had pulmonary metastases of colonic neoplasms previously resected, respectively 3 and 6 years before. After completion of the cardiac procedures, during the rewarming of the patient, the pulmonary resection was performed on a deflated lung, via the median sternotomy. Pulmonary procedures included: right upper segmentectomy (n = 1), left pneumonectomy (n = 1), left interior lobectomy (n = 1), right middle lobectomy (n = 1), left upper wedge resection (n = 1), and right upper lobe wedge resection (n = 1). All patients were extubated on day one. One patient died from rythm disturbances on day 13. All other patients are alive with a mean survival of 30 months. The authors conclude that combined surgery is feasible in selected cases. Sternal approach is not a limitation to pulmonary resection. PMID- 2239040 TI - [Surgical treatment of the sequelae of ischemic postdysplasia femur head necrosis in children. II. Surgical technique]. AB - The author presents its concept concerning the possibilities of the surgical treatment of the sequelae of the postdysplastic necrosis of the femoral head originating from the treatment of congenital dislocation or subluxation of the hip joint. The classification is based on the division according to Bucholz and Ogden into 4 types. Indicated for the surgical treatment are hips with the injury of the type II and III. In Grade II type the joint congruence is not affected and the method of operation is the redirection pelvic osteotomy. In children up to the age of 10 the author applies Salter osteotomy and in elder children and adolescents he performs a triple osteotomy of pelvis. Grade III type is the most severe impairment because of the concurrent defect of the joint congruence, limb discrepancy and extensive anatomic changes of the proximal end of femur. Up to the age of 10 he recommends Salter innominate osteotomy with the simultaneous valgus osteotomy, in elder children he recommends successively a triple pelvic osteotomy and a double intertrochanteric valgus osteotomy. This facilitates a considerable improvement of most hip joints affected in this way and at the same time the compensation of the limb length. PMID- 2239039 TI - [Fournier's gangrene]. AB - Two patients with a necrotizing soft tissue infection of the scrotum and perineum are described. The etiology was found to be a gram negative synergistic gangrene. Patients were managed with extensive necrotectomy with a planned second look operation and supportive antibiotics (aminoglycosides, amoxicillin, metronidazole). Despite this aggressive approach one of the patients died of ongoing necrosis. The therapeutic management for necrotizing soft tissue infection comprises early surgical intervention with supportive antibiotic treatment. Nevertheless the disease is associated with a high mortality rate. PMID- 2239041 TI - [The esthetic effect of surgical treatment of idiopathic scoliosis]. AB - Idiopathic scoliosis has a negative impact on the heart and lungs in the deformed chest, its creates a cosmetic defect, i.e. asymmetry of the paravertebral prominence, shortening of the trunk, asymmetry of the shoulders and protruding scapulae. Later it may cause pain and nervous disorders. In a group of 46 patients aged 15.5 years with thoracic right-sided idiopathic scoliosis the effect of operation by Harrington's instrumentation and spondylodesis on improvement of the curvature and the cosmetic effect were investigated. Preoperative curvature of 69 degrees according to Cobb improved to 35 degrees (by 50%) and the prominence from 38 mm before operation to 23 mm after operation (by 32%). The operation had also a positive effect from the cosmetic aspect which is of great psychological importance for the patients, in particular girls. PMID- 2239042 TI - [Spondylothoracic dysplasia]. AB - The authors describe 4 cases of spondylothoracal dysplasia. In two of them the severity of scoliotic deformity necessitated surgical treatment, the other two cases are under observation, as numerous malformations are at present compensating each other. All of them fall into the type II with a good life prognosis. The analysis of patients and survey of findings from the available literature facilitates a better familiarization with this syndrome. PMID- 2239043 TI - [Tuberculosis of the upper cervical spine]. AB - The authors present a case report on a 25-year-old female patient with the tuberculous spondylitis of 2nd cervical vertebra. For the treatment they choose a two-stage surgical procedure. Within the first stage they removed transorally the focus and filled in the defect in the body of the vertebra with autospongy bone grafts. In the second stage they stabilized the spine from the dorsal approach. Postoperative treatment in the plaster of Paris collar lasted three months. Thus the disease was quickly eliminated. PMID- 2239044 TI - [The tasks and objectives of geriatric orthopedics]. AB - The ageing of population all over the world including Czechoslovakia where the share of people above 60 years of age is 14-15 per cent of the whole population (by the year 2010 this share should reach 20 per cent and a very frequent incidence of diseases and traumatism of osteoarticular apparatus in elderly people necessitates specialized care of geriatric patients. Geriatric orthopaedics is a combination of the principles of internal medicine and orthopaedics applied on old people. Geriatric orthopaedics deals with 3 major problem areas of diseases in old age: 1. osteoporosis, 2. osteo-arthrosis, 3. traumatism. The author concentrates on the problems of diagnostics, prevention and treatment of osteoporosis as well as on its social and economic aspects. He also deals with the incidence, conservative and surgical treatment of osteo arthrosis in old age and with the possibilities of its prevention. Presented are the principles of an up-to-date treatment of geriatric traumatism and the rehabilitation based on the author's experience and recent data from the literature. PMID- 2239045 TI - [Traumatic indications for total hip joint prosthesis]. AB - In the years 1978-1986 the authors implanted 207 total prostheses in patients with the fracture of the femoral neck or after the fractures in the area of the hip joint. 50 patients were operated on for an acute fracture of the neck. The surgical technique in these indications does not differ on principle from the surgical technique of coxarthrosis. They point out a higher number of some peroperative complications. They checked 141 patients with and average follow-up of 47 months. In 4.2 per cent of late complications they reported roentgenological symptoms of loosening. Reoperation because of the loosening of the acetabular component was inevitable in 2.9 per cent of patients. All these cases fall into the group of patients in which the total hip arthroplasty was performed after the fractures of the acetabulum. In no patient it was necessary to reoperate the femoral component. Within the check up the patients underwent roentgenological examination and the result was assessed by the method according to Harris. In total, excellent result was reported in 43.2 per cent of patients, good result in 29.8 per cent, fair result in 14.2 per cent and poor result in 12.8 per cent of patients. With regard to a low number of complications and very good results of the evaluation according to Harris the authors consider total hip arthroplasty in the treatment of post-traumatic conditions for fully indicated. Total hip arthroplasty is indicated also in acute fractures of the femoral neck in which it brings in a short time interval good functional results with minimum complications. A group at risk is represented by patients operated on after the fractures of acetabulum. PMID- 2239047 TI - [Definition of "polytrauma" and "polytraumatism"]. AB - Polytrauma (multitrauma) is a short verbal equivalent used for severely injured patients usually with associated injury (i.e. two or more severe injuries in at least two areas of the body), less often with a multiple injury (i.e. two or more severe injuries in one body area). An important condition for the use of the term polytrauma is the incidence of the traumatic shock and/or hemorrhagic hypotensis and a serious endangering of one or more vital functions of the organism. At least one out of two or more injuries or the sum total of all injuries endangers the life of the injured person with polytrauma. For its variable and non homogeneous content the term polytrauma cannot be used as a final diagnosis without an objective quantification of the extent of the severity of the injury. The author therefore recommends to use this term to express a severe injury endangering the life as a general term which must be necessarily specified by the actual morphological and functional diagnoses. The term "polytraumatism" used in practice is not exactly a synonym of polytrauma, however, it has a direct generalizing relation to it. Polytraumatism embraces the broad health care and general societal problem area relating to severe associated and multiple injuries (i.e. to polytrauma). The author presents the actual classification of polytraumas according to their severity into four, three or two groups. This classification is based on the principles of general quantification of the severity of the injury (from the viewpoint of individual injuries and at the same time from the viewpoint of all concurrent injuries) divided into five or six grades. PMID- 2239046 TI - [Tissue loss injury of the proximal phalanx of the thumb and repair using a rib graft]. AB - In their case report the authors deal with the loss tissue injury of the proximal phalanx of the thumb caused by a circular saw. The first treatment on the day of the injury was carried out at the local clinic, the edges of the wound were trimmed and the residual small bone fragments were removed. Then suture was made of the dorsal aponeurosis and a K-wire was drilled in percutaneously through the distal phalanx into the base of the proximal phalanx in order to maintain the distance between the fragments. Wide-spectrum antibiotics were applied together with antitetanus-toxic injections and anti-gangrenous serum. After 9 weeks when the wound was healed per primam the patient was sent for further treatment to the central clinic. There they introduced extension through the nail of the thumb and left it there for 15 days. 11 weeks after the injury the patients was operated on. A bone graft was made from part of 6th rib and fixed to the residue of the base by a T-shaped plate. The distal phalanx was then transfixed to the bone graft by 2 crossed-K-wires. The wound healed per primam, K-wires were removed after 6 weeks. The grasping function of the hand was preserved, the residual motion was possible in the metacarpophalangeal joint of the thumb, interphalangeal arthrodesis was stable. The patient resumed his original job as a painter. PMID- 2239048 TI - [The information system at the Orthopedic Clinic of the Institute for Physicians and Pharmacists]. AB - Technological progress in the eighties achieved in the development and implementation of computer technology facilitates new approaches to information processing. Informatics becomes one of the key branches of economy of advanced countries. Under the conditions of the present growth of the volume of information also health care must change the classical form of information processing if it is to fulfil its function properly. The consideration is presented on the possibilities of the introduction of computer technology in our clinics and the problems resulting from it. The experience is described with developing a data base information system of the Orthopaedic clinic of the Institute for In-Service Training of Physicians and Pharmaceutists using ADT 4700 minicomputer. PMID- 2239049 TI - [An instrument for injection of bone cements]. AB - The author describes the use of a specially developed instrument, which in combination with Chirana 30 ml syringe for one use facilitates the injection application of bone cement in the implantation of the femoral component of total hip arthroplasty or cervicocapital endoprosthesis of the hip. Emphasis is put on the availability of this instrument for all clinics and on the importance of the application of bone cement under pressure from the view point of longterm results of the above mentioned joint arthroplasty. No evident disadvantages in comparison with imported instruments have been found out. PMID- 2239050 TI - The treatment of infected wounds. Review. PMID- 2239051 TI - Rapid estimation of serum myoglobin concentration during rhabdomyolysis with a latex-agglutination test (Rapi-Tex). AB - A latex-agglutination test (Rapi-Tex) was used for semiquantitative estimation of myoglobin concentration in 89 serum samples obtained from ten patients undergoing lower-limb arterial embolectomy. Each serum sample was tested with Rapi-Tex both undiluted and after 1:50 dilution with saline. The myoglobin concentration was additionally measured with enzyme-immunoassay. In the undiluted samples there were five 'false negative' Rapi-Tex results--two in the myoglobin concentration interval 0-300 micrograms and three in the samples with myoglobin exceeding 25,000 micrograms/l--and four 'false positive' results. None of the diluted samples gave rise to false classification. Using 1:50 diluted serum, the negative predictive value of the Rapi-Tex test for identification of a myoglobin concentration greater than 5,000 micrograms/l was 0.99 (95% confidence limits 0.94-1.00), and the positive predictive value was 1.00 (0.61-1.00). Rapi-tex is concluded to be a useful emergency test for severe hypermyoglobinemia. PMID- 2239052 TI - An improved prognostic index of axillary node involvement in breast cancer incorporating DNA ploidy and tumour size. AB - A multivariate prognostic index based on clinical data and the results of flow cytometry for the grading of breast cancer was evaluated in 117 patients whose disease had been detected and treated by mastectomy with axillary clearance between 1974 and 1976. Survival analysis with Cox's regression model pointed to three important prognostic factors: lymph node involvement (p less than 0.001), DNA ploidy (p less than 0.01) and tumour size (p less than 0.01). These factors were incorporated into a prognostic index, in which the lymph node involvement, DNA ploidy, and tumour size contributed to the index in that order. Logistic discriminant analysis with five year follow-up as the fixed end point (70 alive, 47 dead) gave the same result; lymph node involvement, tumour size, and DNA ploidy were the best prognostic indicators of survival. The result showed that our multivariate prognostic index was more powerful than lymph node involvement alone. The use of this prognostic index is recommended for selecting patients for different treatments. PMID- 2239053 TI - Host defence and bacterial growth in fosfomycin-treated peritonitis. Experimental observations in pigs. AB - An approximately steady state of bacterial density intraperitoneally has been observed in bacterial peritonitis. This state, which follows an initial (0-4 h) phase of rapid elimination of bacteria, was now studied in a model of porcine peritonitis. Twelve pigs were intra-abdominally infected with 10(10) CFU each of Escherichia coli and Bacteroides fragilis. Six of the pigs received no antibiotic and six were given two doses of fosfomycin (anti-aerobic), 1 g i.v., with the aim of disturbing possible equilibrium between rapid proliferation and destruction of the sensitive E. coli. Levels of fosfomycin up to 90 times the minimum inhibitory concentration (1 mg/l) were detected in the peritoneal exudate, but the antibiotic had no discernible effect on E. coli density or elimination pattern compared with B. fragilis in the same pig or with observations in controls. The results favoured the concept of slow-replicating E. coli and hence declining activity of the defence mechanisms a few hours after the induction of peritonitis. PMID- 2239054 TI - A porcine model for acute distal aortic occlusion. AB - Periarterial and intramural nerves and lymphatics as well as the vascular endothelium may influence pathophysiologic responses to acute arterial occlusion. For study of such pathophysiologic patterns, experimental models resembling the clinical situation are therefore preferable. In this porcine study acute distal aortic occlusion was mimicked by use of a balloon catheter introduced via a vascular graft anastomosed to the lateral aortic wall. Peripheral circulatory disturbance was assessed by measurements of femoral vein blood flow, skin blood flow in the hind foot and oxygen tension in the calf muscle, which verified the degree of ischemia. During the 4-hour ischemic period, repeated arterial and venous blood gas analyses showed increasing acidosis in effluent venous blood from the hind limbs, which after reperfusion slowly normalized. As highly reproducible conditions are achievable with the present experimental model, it can be used for studies of pathophysiologic responses to acute distal aortic occlusion. PMID- 2239055 TI - Indomethacin and pancreatic blood flow. An experimental study in pigs. AB - Indomethacin has been reported to decrease pancreatic blood flow. The drug has been used as an analgesic in acute pancreatitis. As decreased blood flow to the pancreas may detrimentally affect the outcome of acute pancreatitis, we investigated the effects of indomethacin on blood flow in the normal porcine pancreas. Regional blood flows, with special reference to the pancreatic flow, were studied with radioactively labelled microspheres in ketamine-anesthetized pigs before and after intravenous administration of indomethacin 2 mg/kg during 10 min. A transient decrease of cardiac output was seen during the infusion. Basal pancreatic blood flow was significantly increased 10 and 30 min after administration of indomethacin. No significant changes were found in small intestinal or renal blood flow. We conclude that indomethacin does not reduce blood flow in normal porcine pancreas. PMID- 2239056 TI - Local energy metabolism in healing colon anastomosis. An enzyme-histochemical study in rats. AB - Local energy metabolism in healing colonic anastomosis was studied in rats. A one layer, inverting colo-colostomy was performed and frozen sections from the anastomotic area were enzyme-histochemically stained for key enzymes in energy metabolism. Anaerobic metabolism prevailed in the anastomotic area during the first postoperative week. The repair tissue between the inverted colonic leaves showed the first sign of aerobic glycolysis 1 week postoperatively. Increasing lactate dehydrogenase activity, however, was seen from day 3 onwards (simultaneously with revascularization), and indicators for amino acid metabolism, lysosomal activity and metabolism via the pentose phosphate shunt were present even earlier--from day 1 onwards. Anastomotic surgery was followed by severe reduction of metabolism in all layers of the colonic wall 0-5 mm from the anastomotic line. Normal metabolism was not restored until postoperative day 21. These findings should be considered in surgical techniques and post-operative management. PMID- 2239057 TI - Thoracic empyema--a delayed complication of excluded benign thoracic oesophagus. Case report. AB - Delayed 'blow-out' of retained thoracic oesophagus, 2 years after its exclusion for iatrogenic oesophageal perforation, gave rise to thoracic empyema. Oesophageal exclusion performed for benign, non-caustic conditions tends particularly to cause complications. Excision of the oesophageal remnant should therefore be considered in restoration of alimentary-tract continuity. PMID- 2239058 TI - Resectable leiomyosarcoma of inferior vena cava presenting as carcinoma of the pancreas. Case report. AB - A 61-year-old woman was thought to have a cancer of the head of pancreas on ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography (ERCP). At laparotomy, however, the pancreas was normal, and the tumour originated in the inferior vena cava. Histological examination showed a moderately differentiated leiomyosarcoma. The outcome was uneventful after caval resection and reconstruction with a polytetrafluoroethylene (Goretex) patch. PMID- 2239059 TI - Toxicokinetics in clinical toxicology. AB - Toxicokinetics is an essential step in clinical toxicology. The methodology is based on the same parameters which are used in pharmacokinetics. However, the interpretation and the aims are different. For each toxicon, the interpretation of kinetic data needs to take account of the spontaneous toxicokinetics, the factors of variation, the relationship kinetic data and symptoms, the severity and prognosis criteria. The evaluation of treatment has to take account of the global kinetic action of the toxicon during the intoxication and the effects on the symptomatology. The mechanism of toxicity, is an essential item in the interpretation of toxicokinetic data. By the exact knowledge of toxicokinetics, it is possible to determine for each toxicon, the relevant parameters which will be of use in clinical practice. PMID- 2239060 TI - Accidental nasal eucalyptol and menthol instillation. PMID- 2239061 TI - Accidental ingestion of a sterilising tablet (dichloroisocyanurate) by a 28 day old infant. PMID- 2239062 TI - Acute intoxication by ingestion of inorganic mercury salts. PMID- 2239063 TI - Biological valuation of extra-corporeal techniques in acute poisoning. AB - The efficiency of dialysis methods a/o hemoperfusion in acute poisoning cannot be clinically estimated, because: a) Concomitant intestinal absorption, hepatic metabolism and urinary excretion must be taken into account. b) With supportive treatment alone, spontaneous recovery usually occurs in 98% of the intoxications in Intensive Care Units. The efficiency of these methods can only be estimated biologically. Measuring the blood level at the beginning and the end of the treatment as well as measuring the clearances of the drug is misleading. A better method is to measure the amount of extracted drug, either indirectly by calculation (from hourly differences of arteriovenous measures of drug concentration multiplied by the blood flow) or directly by elution of the cartridge or measures in dialysis fluid. Plasma kinetics under dialysis a/o hemoperfusion should be compared with spontaneous toxicokinetic of the substance and not with pharmacokinetic data. The experience of toxicologists has shown dialysis a/o hemoperfusion to be ineffective for drugs with weak extra-cellular distribution (such as Digoxine, Tricyclic drugs, heavy Metals, Colchicine). In the case of intoxication with Paraquat or Paracetamol, there is a negative correlation between the amount of removed intoxicant and the survival: death is likely to occur when the procedure has been very productive. In the case of intoxication by hypnotic drugs, one hemodialysis a/o hemoperfusion allows the removal of an average of 4-12% of the ingested barbiturates, 7-17% of the ingested Meprobamate. Whether these results can be judged satisfactory, life saving of insignificant is largely a matter of personal standards. PMID- 2239065 TI - The role of the laboratory of toxicology in the diagnosis and therapy of the poisoned patient. PMID- 2239064 TI - Current status of antidotal therapies in acute human intoxications. AB - The purpose of this work is a review of usefulness, indications and handling of some antidotes which are at our disposal for therapeutic use since several years, especially naloxone, flumazenil, Fab fragments of digoxin specific antibodies, hydroxocobalamine, 4-methyl-pyrazole, N-acetylcystein or the new metal chelators. Older clinically relevant substances are also reviewed. PMID- 2239066 TI - Specificities of child poisoning. PMID- 2239067 TI - Carbon monoxide poisoning--recent advances. PMID- 2239069 TI - Poisoning by some insecticides, herbicides and fungicides. AB - To avoid accidental poisoning, pesticides must be handled according to prescribed rules. Furthermore, the exact composition of the pesticide formulation should be known. Cases of acute poisoning usually occur by ingestion and less frequently by the other routes. Symptoms may appear immediately but sometimes they can appear later and/or be more prolonged giving rise to delayed death and/or delayed morbidity. Acute poisoning by raticides and by organophosphate insecticides should deserve all our attention. Poisoning by herbicides containing chlorate salts, oxidative phosphorylation uncouplers or bipyridilium derivatives may be particularly dangerous. The ingestion of Paraquat, in particular, which is a veritable lesional poison, could be beyond all therapeutic resources. PMID- 2239068 TI - Caustic intoxication. AB - After a retrospective study of 17 cases of caustic intoxication in the intensive care unit, the epidemiologic, pathophysiologic, clinic and therapeutic aspects are reviewed. The following procedure is suggested: early endoscopies, abstention of any gastric lavage, corticosteroids and empiric antibiotic therapy and the most early possible introduction of a parenteral nutrition. PMID- 2239070 TI - Anticholinergic intoxications. A case report. PMID- 2239071 TI - Self-poisoning treated in an intensive care unit. PMID- 2239072 TI - False negative results in routine analytical toxicology screening in the case of an acute scopolamine poisoning. PMID- 2239074 TI - Weather influence on the prevalence of carbon monoxide intoxications. PMID- 2239073 TI - Strychnine poisoning, hypoxic damage, severe acidosis: a case report. PMID- 2239075 TI - Acute poisoning in a children's hospital: an 8 year experience. PMID- 2239076 TI - Growth hormone secretion patterns in relation to LH and testosterone secretion throughout normal male puberty. AB - Pulsatile growth hormone secretion patterns were studied in relation to LH and testosterone release in 30 healthy prepubertal boys and 2 adult men. Plasma GH was measured every 10 min, plasma LH and testosterone every hour. Night-time GH secretion parameters were 2-3 times higher than daytime values. During daytime, mean GH level and the fraction of GH in pulses increased from Tanner stage G2 to G4 (p = 0.01); during night-time these parameters increased as well (p less than or equal to 0.1) and decreased from stage G5 to adulthood (p = 0.05). GH pulse number did not increase; the number of high-amplitude (greater than 8 micrograms/l pulses, however, increased from stage G2 to G4 (p = 0.05) during the day. Height velocity correlated with their number of high pulses during day and night (tau = 0.39, p less than 0.003). From stage G2 to G4 significant correlations were observed between nocturnal testosterone levels and GH secretion parameters (tau = 0.53-0.57), in contrast to nocturnal LH levels. It is concluded that during puberty 1. GH secretion increases as a result of an increased pulse amplitude; 2. there is no consistent correlation between GH and LH levels; 3. increasing nocturnal testosterone levels are correlated with the increasing GH secretion; therefore GnRH does not seem to influence GH secretion directly, but an indirect effect via testosterone is more conceivable, and 4. height velocity is correlated with the number of high GH pulses. PMID- 2239077 TI - Pulsatile growth hormone release in Turner's syndrome and short normal children. AB - To determine whether the quantitative and qualitative aspects of GH secretion in girls with Turner's syndrome are similar to those of short-normal children we studied the 24-h GH secretion of 10 patients with Turner's syndrome and 9 short normal children with comparable auxological features. GH profiles, obtained by 30 min sampling, were analysed by the Pulsar programme. The pulsatile GH release over the 24 h in Turner's syndrome was similar to that in normal children. However, when the GH release over the 12 day and night hours were separately analysed, only normal children showed a night-time increase in the sum of peak amplitudes. Moreover, patients with Turner's syndrome had significantly decreased number and frequency of peaks in the night-time compared with short children. In short-normal children but not in Turner's syndrome, height velocity was related to the 24-h integrated concentration of GH, area under the curve over zero-line and over baseline, sum of peak areas, and amplitudes. Night-time GH area over zero-line and over baseline, mean peak amplitude, height area, sum of peak area and amplitudes were positively correlated with height velocity in short children, whereas in Turner's syndrome height velocity was related to daytime parameters only. In conclusion, girls with Turner's syndrome have a discrete pattern of pulsatile GH release. However, the relation of GH secretion to growth in these patients, is uncertain. PMID- 2239078 TI - Pharmacokinetics of the antiprogesterone RU 486: no correlation to clinical performance of RU 486. AB - The pharmacokinetics and metabolism of RU 486 were characterized in 17 women who received a single dose of 600 mg of RU 486 for termination of an early unwanted pregnancy. Based on the clinical outcome and serum chorionic gonadotropin values, the subjects were divided into two groups: those who aborted completely (i.e. responders: N = 13) and those who did not respond to RU 486 treatment (i.e. non responders: N = 4). The serum levels of RU 486, the monodemethylated, didemethylated and hydroxylated metabolites of RU 486 were measured by HPLC preceded by column chromatography. There were no significant differences in the serum levels of RU 486 or its metabolites between the two groups. The serum concentrations of alpha 1-acid glycoprotein, the binding protein for RU 486, were quantitated by immunoturbidimetry. The alpha 1-acid glycoprotein concentrations were similar in responders and non-responders. The metabolism of RU 486 was also studied by fractionating extracts of serum pools of responders and non-responders on thin-layer chromatography, and subsequent RIA analysis of the eluates of the sliced thin-layer chromatography. Spots with similar distribution and percentages of cross-reactivity were found in both groups on the chromatography; the results were also similar to those from a serum pool to which synthetic RU 486 and its three metabolites had been added. Hence it is concluded that failure to abort in response to RU 486 therapy is not associated with altered pharmacokinetics or metabolism of RU 486. PMID- 2239079 TI - Antithyroid drug treatment of Graves' disease in pregnancy: long-term effects on somatic growth, intellectual development and thyroid function of the offspring. AB - With regard to their thyroid function, somatic and intellectual development, we compared 17 children of 13 hyperthyroid mothers (group I) receiving antithyroid drug treatment during their pregnancies with 25 children of 15 mothers who were euthyroid without any antithyroid treatment during their pregnancy (group II). Mean duration of maternal treatment was 3.5 months in group I, using carbimazole or thiamazole (N = 12) and propylthiouracil (N = 1). Age at examination in group I was 7.2 +/- 6.2 years, in group II 8.7 +/- 7.1 years (mean +/- SD). Both groups showed no significant differences in the results of the clinical examination and in the degree of their mental and psychomotoric development at the time of study. We found the mean birth weight of the infants in group I significantly lower than in group II (3165 +/- 339 vs 3666 +/- 670 g, p less than 0.03). The individual birth weights, however, were normal for gestational age. The body weight difference between groups disappeared during the further somatic development of the children. The serum concentration of free thyroxine in group I was significantly higher than in group II (17.2 +/- 2.4 vs 14.9 +/- 1.9 pmol/l, p less than 0.003), but fell in both groups within the normal range. The evaluation of the psychomotoric and intellectual capacity of the children at different developmental stages showed no abnormalities detectable by our tests. Thus, in the children of the two groups we found no adverse effects of a maternal antithyroid drug treatment during pregnancy or of inactive maternal Graves' disease alone, neither on thyroid gland size and function nor on the physical or intellectual development, after the neonatal period. PMID- 2239081 TI - Epidermal growth factor and platelet-derived growth factor in blood in diabetes mellitus. AB - Epidermal and platelet-derived growth factors are potent mitogens for many types of cells, including smooth muscle cells. Epidermal growth factor in blood of humans is present both in platelets (as reflected in its serum level) and in plasma, the source(s) of which remains unknown. We assayed its level in 82 diabetic patients and 53 age-matched controls. In diabetes, epidermal growth factor level was increased in serum (191 +/- 43 vs 155 +/- 64 pmol/l, p = 0.0002) and plasma (53 +/- 9 vs 38 +/- 14 pmol/l, p less than 0.0001), without any difference between the patients with and without complications. Platelet-derived growth factor level was assayed only in serum of 19 patients with uncomplicated diabetes and found elevated (222 +/- 47) as compared with 13 controls (160 +/- 26 pmol/l), (p = 0.0002). Type of diabetes, its duration, mode of therapy, control, presence of retinopathy or albuminuria (in case of epidermal growth factor), as well as C-peptide age and sex did not correlate with epidermal or platelet derived growth factor levels. Serum but not plasma epidermal and platelet-derived growth factor were negatively correlated with serum creatinine (correspondingly, r = -0.373, p = 0.0008 and r = -0.564, p = 0.0285). It is concluded that diabetes itself and not its complications cause increased levels of epidermal growth factor in plasma and serum and of platelet-derived growth factor in serum. PMID- 2239082 TI - The corticotropin-releasing factor test in the differential diagnosis of Cushing's syndrome: a comparison with the lysine-vasopressin test. AB - The diagnostic accuracy of the CRH test was compared with that of the LVP test in 28 consecutive patients with ACTH-dependent Cushing's syndrome. A false negative response to CRH was found in 3 of 21 patients with pituitary-dependent Cushing's disease and to LVP in 4. The 7 patients with ectopic ACTH secretion were unresponsive to CRH, whereas 2 did respond to LVP. CRH and high-dose dexamethasone tests combination led to concordant results in 79% of patients. In all cases the etiological diagnosis suggested was correct. LVP and high-dose dexamethasone tests combination led to concordant results in only 71% of patients and the etiological diagnosis suggested was erroneous in one. Individual tolerance to the CRH test was also clearly better than that to the LVP test. It is concluded that the CRH test, alone or in combination with the high-dose dexamethasone test must be preferentially used to the LVP test in the differential diagnosis of ACTH-dependent Cushing's disease. PMID- 2239083 TI - Influence of growth hormone on the immunosuppressive effect of prednisolone in mice. AB - Growth hormone can be used to counteract some catabolic effects of long-term administration of glucocorticoids, such as impairment of growth in children and osteoporosis. However, owing to its immunostimulatory properties the hormone may counteract the effect of glucocorticoids on the immune system. To investigate this question we administered different doses of hGH (4, 8, 40 IU/kg) to C57/Bl/6J mice treated for two days with prednisolone, and evaluated thymus and spleen parameters and natural killer activity. Growth hormone at the dose of 4 and 8 IU/kg reversed prednisolone-induced reduction of spleen and thymus weight and cellularity, whereas the highest dose showed to be immunosuppressive in itself. Two days after treatment withdrawal, a recovery of spleen parameters was evident, whereas the thymus was still suppressed by preceding prednisolone or hGH (40 IU/kg) treatments. The pattern of natural killer activity displayed by the splenocytes resembled that present under treatment. In a second experiment prednisolone, administered for 10 days, drastically reduced the number of viable spleen and thymus cells as well as the relative spleen and thymus weights, an effect reversed by concomitant administration of hGH (0.8, 4, 8 IU/kg). Natural killer activity, which was significantly depressed by prednisolone, was restored by the intermediate GH dose only. The 8 IU/kg GH dose was immunosuppressive in itself. PMID- 2239080 TI - Monoclonal antibodies reveal circulating growth hormone of high molecular weight not detectable by conventional assays. AB - A radioimmunoassay based on a monoclonal antibody. Mc-ab 1, which was raised against growth hormone but cross-reacted with human placental lactogen yielded higher GH immunoreactivity levels in serum than one based on a polyclonal antiserum. This discrepancy was noted in subjects with normal GH secretion as well as in patients with GH insufficiency. To characterize this GH immunoreactivity detected by Mc-ab 1, affinity purification and molecular sieve chromatography of serum were performed. High molecular weight proteins with GH immunoreactivity were found with both techniques. These proteins were associated with carbohydrates. Affinity cross-linking showed specific binding of radiolabelled GH to high molecular weight proteins in the serum. After fractionation of serum, the GH immunoreactivity became detectable by the polyclonal antiserum assay as well as by an immunoradiometric assay. GH immunoreactive material with an approximate mass of 80 kD was subjected to isoelectric focusing. When GH immunoreactive fractions at pH 5 were re chromatographed, GH immunoreactivity was recovered in the elution volume corresponding to monomeric GH. Our results show that sera from normal subjects as well as from patients with deficient GH secretion contain notable amounts of high molecular weight GH which is undetectable by antibodies generally used for GH measurements, but which can be revealed after fractionation of serum. PMID- 2239084 TI - The source of cholesterol for progesterone synthesis in cultured preovulatory human granulosa cells. AB - There are three possible sources of cholesterol for immediate use in progesterone production by preovulatory human granulosa cells: follicular fluid high-density lipoprotein, de novo synthesis of cholesterol, and performed intracellular cholesteryl ester stores. In the present study these three alternatives were investigated. First, an in vitro model was established that mimics the preovulatory environment, including short-term cultures and use of autologous follicular fluid in the culture medium, instead of serum. Using this model it was found that the presence of high-density lipoprotein from follicular fluid in the culture medium did not affect the synthesis of progesterone by the granulosa cells. Next, addition of inhibitors of de novo sterol synthesis, like low-density lipoprotein, 25-OH cholesterol and compactin to the culture medium, did not reduce [14C]acetate incorporation into sterols and steroids by the cells. The sterol synthesis was accordingly interpreted to be at a low and therefore uninhibitable level. Finally, the content of free and esterified cholesterol in freshly isolated granulosa cells was found to be 50 +/- 7 and 52 +/- 13 pmol/mg cell protein, respectively. We suggest that neither follicular high-density lipoprotein nor endogenous synthesis is the immediate cholesterol source for the progesterone production in preovulatory human granulosa cells. However, granulosa cells have a large store of cholesteryl esters that may provide free cholesterol for the preovulatory progesterone production. PMID- 2239085 TI - Intravenous administration of recombinant IGF-I lowers serum GHRH and TSH. AB - Recombinant IGF-I was administered as an iv bolus of 75 micrograms/kg to 10 patients with Laron type dwarfism (3 children aged 9, 11 and 12 years and 7 adults aged 30.6 +/- 3.5 years) and to 8 healthy subjects (mean age 19.9 +/- 12.1 years) and determinations of IGF-I, GHRH, hGH, TSH, and glucose were made before and at 2, 5, 15, 30, 60, 90, and 120 min. The following effects were observed: a. an immediate, marked and sustained drop in blood glucose (p less than 0.001), more prolonged in the patients; b. in both groups, a dramatic rise in plasma hGH (p less than 0.01) which peaked at 60-90 min; in the patients this occurred after an initial immediate fall in plasma hGH (p less than 0.01); c. a progressive decrease of plasma GHRH and TSH (p less than 0.05, 0.02) in both patients and healthy controls. An hypothesis is put forward that acute and time-limited release of somatostatin by IGF-I is the main cause of the hormonal changes registered. As the IGF-I bolus also suppressed circulating insulin levels, the hypoglycemia is considered to be a direct effect of IGF-I. PMID- 2239086 TI - Evidence for a long-term storage of calcitriol in a patient with 1-alpha hydroxylase deficiency and rickets. PMID- 2239087 TI - Thyroid size and function in healthy pregnant women with thyroid autoantibodies. Relation to development of postpartum thyroiditis. AB - In a study of postpartum thyroiditis, thyroid function and ultrasonically determined thyroid size were evaluated in 36 thyroid autoantibody positive healthy women during pregnancy and the first postpartum year. Twelve women (33%) developed postpartum thyroiditis with permanent thyroid dysfunction in three. However, only one woman had symptoms and needed treatment. The most common type of thyroid dysfunction was a transient hyperthyroid phase as seen in 7 women. A significant increase by 20-30% in mean thyroid volume during pregnancy was demonstrated independent of development of postpartum thyroiditis. We conclude that initial thyroid volume or changes during pregnancy and post partum are not useful indicators of the development of postpartum thyroiditis. The fact that the condition is oligosymptomatic suggests that screening procedures are necessary if one wants to diagnose the earliest phases of postpartum thyroiditis. PMID- 2239088 TI - Parathyroid localization by 201Tl-99mTc subtraction scintigraphy: results in secondary hyperparathyroidism. AB - Subtraction scintigraphy with 201Tl and 99mTc for parathyroid localization was performed preoperatively in 13 patients with chronic renal failure and secondary hyperparathyroidism. Twenty of the 37 examined pathological glands were predicted correctly (sensitivity 54%). In 3 patients with recurrent hyperparathyroidism after surgery all pathological glands found at second operation had been detected correctly by subtraction scintigraphy. We conclude that this localization method has a limited value when used prior to first neck exploration in secondary hyperparathyroidism. In persistent hyperparathyroidism after surgery it may play a useful role in localizing missed and ectopic glands. PMID- 2239089 TI - Thyroid peroxidase/microsomal antibodies are not identical with thyroid cytotoxic antibodies in autoimmune thyroiditis. AB - Cytotoxic activity in sera of patients with Hashimoto's thyroiditis was measured with an antibody-dependent cell-mediated cytotoxicity assay. Cytotoxicity was determined in a 51chromium release assay using human thyroid cell targets incubated with heat-inactivated serum or IgG from patients with Hashimoto's thyroiditis. Effector cells were obtained from peripheral mononuclear cells of normal subjects. Cytotoxicity was significantly increased in patients with Hashimoto's thyroiditis (median specific lysis 20.2%, range 2.1-58.8) compared with normals (median specific lysis 8.1%, range 0-19.5; p less than 0.00001). The amount of percent specific lysis did not correlate with the titres of microsomal antibodies determined by different methods: passive hemagglutination technique (r = 0.2), enzyme immunoassay with microsomal antigen (r = 0.16), and radioimmunoassay for thyroid peroxidase antibody (r = 0.02). The cytotoxic activity was located in the IgG fraction, both in microsomal antibody positive and negative sera. After pre-incubation of microsomal antibody/thyroid peroxidase antibody positive or negative sera with purified thyroid peroxidase followed by analysis in the antibody-dependent cell-mediated cytotoxicity assay, cytotoxicity decreased in only 2 cases but was unchanged in the remaining sera. Western blot experiments with solubilized thyroid membranes and immunoblotting with cytotoxic positive/microsomal antibody negative sera showed no binding to thyroid peroxidase. Our data suggest that cytotoxicity in sera from patients with Hashimoto's thyroiditis is not mediated by antibodies against thyroid peroxidase, but by antibodies not yet identified. PMID- 2239090 TI - Diurnal variation in melatonin effect on adenosine triphosphate and serotonin release by human platelets. AB - The effect of the pineal hormone melatonin on adenosine diphosphate-induced human platelet aggregation and adenosine triphosphate release was assessed in platelet rich plasma obtained from normal volunteers at 08.30 and 20.30 h. In 10(-7)-10( 5) mol/l concentrations melatonin inhibited ADP-induced platelet aggregation only in the evening (p less than 0.05). ADP-induced ATP release, an index of platelet secretory processes, showed a generally greater, dose-dependent inhibition after adding melatonin (10(-9)-10(-5)mol/l) at 20.30 h as compared with 08.30 h. The inhibitory activity of melatonin (10(-9)-10(-5) mol/l) on [3H]serotonin release elicited by thrombin in washed human platelets obtained from normal volunteers was dose-dependent; the effect was generally greater at 20.30 h. The activity of the potent platelet anti-aggregating agent prostacyclin did not exhibit diurnal differences with respect to impairing ADP-induced platelet-rich plasma aggregation. These results indicate the existence of a diurnal variation of sensitivity to melatonin in human platelets. PMID- 2239091 TI - Action and formation of inositol bisphosphate and inositol trisphosphate in rat anterior pituitary cells. AB - Inositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate, administered exogenously at a concentration of 3 x 10(-5) mol/l increased LH release in superfused rat pituitary cells by 950 +/- 267% and 281 +/- 83%, respectively. This stimulatory effect was reversible and dose-dependent. Other inositol phosphates (inositol 1-monophosphate, inositol 1,4,5,6-tetrakisphosphate, inositol 1,3,4,5,6-pentakisphosphate and inositol 1,2,3,4,5,6-hexakisphosphate), tested in vitro, did not significantly influence LH release. In saponin permeabilized cells, the rate of basal and stimulated LH release was twice that in non-permeabilized cells. Penetration of inositol bisphosphate and inositol trisphosphate into saponin-treated pituitary cells did not increase the secretory potency of these agents compared with their effect on non-permeabilized cells. The new findings document that inositol trisphosphate formation occurs within 5 45 s after GnRH (10(-7) mol/l) administration and seems to be involved in mediating the rapid, first phase of LH release, whereas inositol bisphosphate formation occurs after 3-15 min and is probably related to later phases of LH secretion. Our results suggest that inositol bisphosphate and inositol trisphosphate are important regulators of the release of luteinizing hormone and can exert their effects not only intracellularly, but also extracellularly. PMID- 2239092 TI - Relationship between molecular structures of sugars and their ability to stimulate the release of glucagon-like peptide-1 from canine ileal loops. AB - The structure-activity relationship of sugars inducing secretion of glucagon-like peptide-1 from the gut was examined using intestinal loops prepared from the terminal portion of the ileum of dogs. The plasma glucagon-like peptide-1 concentration in a mesenteric vein draining only the looped region of the intestine was increased after infusion of 139 mmol/l solutions of D-glucose, D galactose, D-glucuronic acid, 3-0-methyl-D-glucose, maltose, sucrose or maltitol into the intestinal lumen, but not after infusion of solutions of D-fructose, D fucose, D-mannose, D-xylose or lactose. The increases in plasma glucagon-like peptide-1 concentration correlated with the corresponding increases in glucagon like immunoreactivity induced by these sugars. The plasma glucose level of the regional mesenteric vein increased significantly from the basal level after instillation of D-glucose, but not after instillation of other sugars. It is suggested that cells of the gut have a glucose sensor for release of products of the glucagon gene and that this sensor has specific steric requirements. The sugars that induced glucagon-like peptide-1 release share the molecular features of electron density near C(6), an equatorial hydroxyl at C(2), and an axial hydroxyl at C(1), which could account for their recognition by the glucose sensor to initiate the releases of glucagon-like peptide-1 and glucagon-like immunoreactivity. PMID- 2239093 TI - Parathyroid hormone and calcitonin may modulate hepatic IGF-I production in calves. AB - Four young milk-fed calves were fitted with catheters chronically implanted in the mesenteric, portal and hepatic veins and in the hepatic artery, and with electromagnetic blood flow probes in the portal vein and hepatic artery, allowing continuous measurement of IGF-I hepatic production. According to a latin square design, these calves received iv mesenteric infusion of calcium (Ca2+; 5 mg/kg) or synthetic salmon calcitonin (sCT; 1 microgram/kg), or synthetic bovine parathyroid hormone (1-34) (bPTH; 1 microgram/kg), or solvent alone (1.2 ml/kg). Ca2+, sCT or bPTH had no significant effect on portal vein or hepatic artery blood flow. Hypercalcemia observed following Ca2+ infusion did not significantly modify hepatic IGF-I production. sCT decreased plasma Ca2+, inorganic phosphorus and GH concentrations and hepatic IGF-I production. bPTH induced a slight hypercalcemia and hypophosphatemia. It had no significant effect on plasma GH concentration, but increased significantly hepatic IGF-I production. Thus, the anabolic effects of PTH on bone may be partly mediated through an increase in hepatic IGF-I production. PMID- 2239095 TI - [Echographic specificity in the early diagnosis of human hydatidosis]. AB - Ultrasonography (US) were used for screening of hydatid disease in 1321 asymptomatic individuals fron Rio Negro Province, Argentina. A total of 76 positive subjects were identified with possible hydatid disease. Surgery was performed in 30 patients, conforming in 28 of them sonographic diagnosis (93.34%). PMID- 2239094 TI - Interleukin 1 beta and tumour necrosis factor alpha stimulate the release of gonadotropin-releasing hormone and interleukin 6 by primary cultured rat hypothalamic cells. AB - The abilities of recombinant human interleukin 1 beta and tumour necrosis factor alpha to induce release of GnRH and interleukin 6 from primary culture of rat hypothalamic cells were examined. The effect of estradiol on the release of interleukin 6 by these cells was also tested. Both interleukin 1 beta and tumour necrosis factor alpha caused significant stimulation of GnRH secretion from the hypothalamic cells within 5 min. The hypothalamic cells secreted interleukin 6 spontaneously, and their secretion over 24 h was stimulated dose-dependently by interleukin 1 beta, tumour necrosis factor alpha and estradiol. These results suggest that interleukin 1 beta and tumour necrosis factor alpha stimulate the secretions of GnRH and interleukin 6 in the hypothalamus, and that these cytokines may be involved in the mechanism of GnRH secretion in the hypothalamus. PMID- 2239096 TI - [Evaluation of esophageal endoprosthesis]. AB - In 60 patients with either non operable esophageal pathology on neighbouring organs pathology with esophageal involvement, esophageal endoprosthesis therapy was assessed. The various implantation techniques are described. Main causes for implantation were epidermoid esophageal carcinoma in 48 instances and gastric adenocarcinoma with esophageal involvement in 9 cases. The causes most frequently associated with early morbimortality were perforation in 4. All cases were medically treated with a 16.9% mortality rate (10 cases), due to broncoaspiration as main cause. Endoscopic reimplantation of the prosthesis was the treatment of choice in perforated cases. PMID- 2239097 TI - [Percutaneous hepatic biopsy puncture in patients with hemostasis disorders. A new technique]. AB - In order to avoid the inconveniences of the trans-jugular liver biopsy, a modified percutaneous liver biopsy with embolization has been performed in 27 patients with chronic hepatic diseases with or without hemostatic disorders. By means of a sheath and a Menghini or Tru Cut needle type, an embolization of the needle tract was carried out utilising coagulations factors (I, IIa and XIII). All procedures were laparoscopically visualised and the "Hepatic bleeding time" measured. With or without embolization, the "Hepatic bleeding time" found was 0-6 seconds and 2-6 minutes, respectively. This modified technic is a safe and effective method for high risk bleeding patients and no hemorrhagic complications postprocedure observed. PMID- 2239098 TI - [Atypical chest pain: study by the hydrochloric acid provocation test]. AB - Evaluation by means of gastroenterological and cardiological methods. The purpose of this paper was to study the origin of chest pain (CP) in patients with normal and pathological coronary arteries as characterized by coronary arteriogram (CA). Sixteen normal control individuals (X 27 years -7 females and 9 males) were studied by means of esophageal manometry (EM) with a 3 way catheter perfused by a low compliance capillary system. Twenty-one patients with chest pain were studied and divided according to coronary arteriogram in normal (NC) and pathological arteries (PC). They were simultaneously studied by means of EM, heart rate/pressure product (RPP), and 12 lead ECG monitoring. After a basal period they were given a Bernstein's provocative chest pain test, and after each of its stages we determined in a simultaneous fashion CP, EM, ECG and RPP. In 61.9% of the patients abnormal basal EM was found. It was characterized by increase in HPZ, duration, propagation velocity and pressure of the peristaltic waves: as well as an increase in the percentage of aperistaltic waves. In 14.2% of the patients the Hydrochloric provocative test was positive. The only statistically significant datum was the heart rate/RPP relationship. We conclude that in future studies it would be of interest to combine 24 hour monitoring EM and pH as well as a more sensitive provocation test such as edrophonium chloride. PMID- 2239099 TI - [Peutz-Jeghers syndrome: a case report]. PMID- 2239100 TI - [Non-invasive staging in liver cirrhosis]. PMID- 2239101 TI - Quantitative genetic analysis of longitudinal trends in height: preliminary results from the Louisville Twin Study. AB - A preliminary series of quantitative genetic models was applied to a subset of longitudinal height data, spanning birth to maturity, gathered from twin families in the Louisville Twin Study. Descriptive Cholesky factor parameterization was found to give more satisfactory results than did a system of constraints based on a model of developmental transmission of a time-constant and time-specific factors. The results from application of two autosomal sex-limitation models are contrasted with those from a model specifying both autosomal and sex-chromosomal patterns of inheritance. The latter model was more conducive to parameter reduction. Although these models do not constitute conclusive tests of autosomal sex-limitation versus sex-linkage, the more parsimonious model is consistent with previous research suggesting a stature locus on the long arm of the Y chromosome. Heritability of height is estimated at about 90% or greater from 6 years of age on. Substantial and fairly constant longitudinal genetic correlations are found from 3 years of age on. Shared environmental effects unrelated to parental height were seen for birth length, corrected for gestational age, to height at 3 years of age, but these are not satisfactorily differentiated from possible twin effects in the present sample. The genetic consequences of assortative mating are emphasized since failure to take assortment into account can lead to overestimation of shared environmental effects and under-estimation of genetic effects. The results indicate that about 20% of within-gender variability for mature height can be attributed to the genetic consequences of assortment, even though the phenotypic marital correlation of 0.22 is quite modest. The importance of testing the assumption of multivariate normality underlying the application of the method of maximum-likelihood is also highlighted. PMID- 2239102 TI - Simultaneous genetic analysis of longitudinal means and covariance structure using the simplex model: application to repeatedly measured weight in a sample of 164 female twins. AB - The simultaneous analysis of means and covariance structures is applied to longitudinal twin data. Body weight was measured on six occasions in a sample of young female MZ and DZ twins. When average body weight at the first measurement occasion, as well as the increments in weight at later occasions, are specified in the genetic part of the model that also adequately explains the covariance structure, a good fit is obtained. In this application the increase in body weight at each occasion is weighted by the square root of the genetic variance innovation terms that represent the new genetic variance entering into the process. PMID- 2239104 TI - Genetic influences on respiratory sinus arrhythmia across different task conditions. AB - Respiratory sinus arrhythmia (RSA) has been shown to be a sensitive index of vagal cardiac control. We studied the genetic and nongenetic influences on individual differences in RSA in a sample of 160 adolescent twins. RSA was measured during rest and across two different tasks. Results show that heritability is task dependent. The amount of genetic variance is the same, however, during rest and task conditions. Because nonshared environmental variance decreases during tasks, heritability is larger for RSA measured under more stressful conditions than for RSA as measured during rest. Multivariate models assessed the continuity of the genetic and environmental influences and show genetic influences to be the same across different conditions, while environmental influences are different. More specifically, a one-factor model is found for genetic influences and a second-order autoregressive model for the environmental factors. PMID- 2239103 TI - Incorporation of twins in the regressive logistic model for pedigree disease data. AB - Segregation and twin disease concordance analyses have assumed a theoretical underlying liability following a multivariate normal distribution. For reasons of computation, of incorporation of measured explanatory variables, and of testing of fit and assumptions, newer analytical methods are being developed. The regressive logistic model (RLM) relies on expressing the pedigree likelihood as a product of conditional probabilities, one for each individual. In addition to logistic regression modelling of measured epidemiological variables on disease prevalence, there is modelling of vertical transmission, of transmission of unmeasured genotypes and of sibship environment. This paper discusses methods for the analysis of binary traits in twins and in pedigrees. Some extensions to the RLM for pedigrees which include twins are proposed. These enable exploration of twin concordance in the context of the twins' common parenthood, the sibship similarities within the family, and the twins' similarity in age, sex, genes and environment. PMID- 2239105 TI - Genetic and environmental influences on special mental abilities in a sample of twins reared apart. AB - The Minnesota Study of Twins Reared Apart has conducted comprehensive medical and psychological assessments of monozygotic (N = 49) and dizygotic (N = 25) twin pairs, separated early in life (average age of separation = 0.3 and 1.1 years, respectively) and reared apart during the formative years (average age of reunion = 30.3 and 37.2 years, respectively). The twins are administered two special mental ability batteries. The Hawaii Battery (H-B), supplemented by several Educational Testing Service tests, is administered toward the beginning of the assessment week. The Comprehensive Ability Battery (CAB) is administered toward the end of the assessment week. All data are age- and sex-corrected. The average MZA and DZA intraclass correlations for the 15 H-B subtests were 0.45 and 0.34, respectively, and the average MZA and DZA intraclass correlations for the 13 subtests of the CAB were 0.48 and 0.35, respectively. Biometric model-fitting of these data indicate an average heritability of about 0.50. Data for groups of subtests in the Verbal, Spatial, Perceptual Speed and Accuracy and Memory domains were compared to a meta-analysis of the special mental ability findings in the ordinary twin literature. The Spatial domain appears to yield the highest and the Memory domain the lowest heritabilities. PMID- 2239106 TI - Genetic influences on neonatal temperament. AB - The genetic contribution to temperament was assessed during the neonatal period in 172 newborn infants from 47 pairs of monozygotic (MZ) and 39 pairs of same-sex dizygotic (DZ) twins. Zygosity was not related to the neonatal temperament variables. Examination of the scores for twin concordance indicated significant within-pair concordance in temperament ratings, but MZ twins were not more like each other than DZ twins. The results suggested that neonatal temperament was influenced by environmental factors. Further analyses indicated that neonatal temperament was influenced by perinatal variables such as birth weight, 1- and 5 minute Apgar scores, and number of days spent in the hospital. It was concluded that there was no clear pattern of genetic influence on neonatal temperament, and that nonshared environmental factors were an important source of variance for temperament during this period. PMID- 2239107 TI - Living habits and personality development of adolescent twins: a longitudinal follow-up study in a birth cohort from pregnancy to adolescence. AB - The living habits of 289 twins in a one-year birth cohort beginning during pregnancy and followed up to adolescence were compared with those of 11,623 singletons and two sets of controls matched either by maternal factors and place of residence only or by these and perinatal morbidity, all from the same cohort. The twins went in for sports more often than the singletons or any kind of controls. A nonsignificant trend was found indicating that twins smoked less often than their matched controls. The twins also used alcohol less often than their controls. The intrapair similarities of twins were higher than the similarities of twins and either type of controls in all four variables tested: sports, smoking, use of alcohol, as well as having been drunk. PMID- 2239108 TI - Qualitative and quantitative aspects on mathematics achievement in MZ and DZ twins. AB - Mathematics achievement test results have been collected for 22 MZ and 24 DZ same sex twin pairs in the Swedish compulsory school. The twins were approximately 11 13 years of age and attended grades 4, 5, or 6. The twin pairs were part of a larger collaborative study between Israel and Sweden (the KAM-project). Teachers were asked how they planned and evaluated their work in the subjects Swedish and Mathematics. In addition to this, results for the twins on Maths tests given by the teachers in their regular work were collected. These tests were thus used by the teachers as an instrument to evaluate the educational process. Intrapair similarity for MZ and DZ twins has been compared for qualitative and quantitative aspects of the Maths tests. Different tests were used by the teachers but the same criteria have been used in the comparison. MZ twins are somewhat more similar than DZ twins for both the qualitative and quantitative aspects. Only one quantitative aspects, however, percentage of correct answers, shows a significant difference between the twin categories. A comparison was also made of intrapair similarity in classes, where the teachers differed according to planning and evaluation of their education. Irrespective of that, the MZ twins seemed to be more similar than the DZ twins in number of correct answers on the Maths tests. Educational implications are discussed. PMID- 2239109 TI - "Twins in school". An Australia-wide program. AB - The multiple birth family is more likely to have a dispute with the education system than with any other service. So many potential areas of conflict exist over the abilities and behaviour of multiples and over such issues as separation or keeping back one twin. One reason for disputes is the lack of good data to adequately reflect the different perspectives of parents and teachers and the differing needs of families: the same solution does not apply to all. To provide the first large-scale data base and building upon an initial survey of 85% of all primary school teachers in South Australia, the LaTrobe Twin Study and AMBA worked with Education Departments to set-up in each state Education Research Teams (ERTs) of parents of multiples who were also teachers. The ERTs were crucial in three phases. 1) Developing and circulating questionnaires and publicising the nationwide survey. 784 families and 1264 teachers of their children completed these questionnaires, many reporting that simply having to address the issues raised in the questionnaire was a valuable learning experience. 2) Exploring the data base. Issues arising included the very different bases on which parents and teachers judged separation desirable, with teachers emphasising the unsubstantiated claim that separation is essential to individual development. Separation became more common over the first three years of schooling but 20-25% of twins separated one year were back together the next. 3) Running regional meetings of parents, teachers and administrators to discuss the results and to pool experiences and plan policies at the local level. A need clearly exists to improve the level of consultation between families and school personnel and to ensure the widespread availability of information which identifies key issues in making decisions for that multiple birth family. PMID- 2239110 TI - Permissiveness-restrictiveness for twins and controls in two educational settings: The Swedish compulsory school and the Israeli kibbutz. AB - In a previous longitudinal twin project a model was developed for studying heredity-environment interaction. One important environmental dimension in this model is permissiveness-restrictiveness. The purpose of the present study has therefore been to investigate perceived and imposed restrictiveness at the societal and classroom level and possible interactional effects on pupil behavior. Results are reported from grade 4 to grade 6 in Israeli kibbutzim and Swedish compulsory school. One major finding is that no systematic differences have been found between twins and controls in the two countries. In both Swedish schools and Israeli kibbutzim permissiveness-restrictiveness will vary depending upon perspective (perceived or imposed) and upon content (type of subject or rule breaking activity). Preliminary within-pair comparisons for the Swedish twins are reported for different types of test results. In agreement with the model, logical abstract thinking as well as reading and mathematics achievement seem to be less influenced by hereditary factors in a restrictive educational setting than in a permissive one. PMID- 2239111 TI - What information should the multiple birth family receive before, during and after the birth? AB - Advances in the management of the multiple pregnancy and delivery must be accompanied by corresponding improvements in service access outside key centres and especially in the information families receive about what may happen during or after the pregnancy. A major review of birthing services in Victoria has focussed attention on four areas where the quality of information is often inadequate. 1) Prepregnancy and the standard of counselling about the incidence of multiples as a result of fertility drugs and in vitro fertilization procedures and about problems which may accompany a multiple birth. 2) Antenatal: At what stage of the pregnancy should parents be told of the multiple pregnancy and how should monitoring of the mother and procedures such as bedrest take into account what are often conflicting demands within the family? 3) Perinatal: Families are frequently illprepared for a cesarean delivery and for the procedures for premature multiples. The problem is often compounded by separation of the mother from one or both twins. While bereavement services are improving, much still needs to be learned about handling congenital abnormalities in one or more multiples. 4) Postnatal: Irrespective of the level of prenatal advice, families greatly underestimate the workload with multiples. The resulting stress contributes to the incidence of postnatal depression, child abuse and divorce now being reported from multiple birth families. Some suggestions are made from social psychology and genetic counselling about how families can best handle risk information to achieve the goal of neither under- nor overestimating the risks at these different stages of the multiple pregnancy. PMID- 2239112 TI - What is it like to be a parent of twins? AB - A questionnaire was given to parents of twins concerning their perceptions of dependency and similarity in their twin children. Also, the parents were asked if they tried to influence their children to become more dissimilar. 70 same-sex twin pairs (35 MZ and 35 DZ) were included in the study and a questionnaire was sent both to the mother and the father of the twins. The twins were approximately 12 years old and attended grade 4, 5 or 6 in the Swedish compulsory school. Results indicated that parents consider MZ twins to be dependent upon each other and to spend more time together. This was especially evident for girls. If the twins had a free choice they would also tend to choose similarly. This trend was also more pronounced for the MZ girls. Irrespective of zygosity, most parents reported that they did not try to influence their children. In the case of MZ twins this will probably make them become more similar over time. Differences between maternal and paternal answers tended to be nonsignificant. PMID- 2239113 TI - Ventilation-perfusion relationships and atelectasis formation in the supine and lateral positions during conventional mechanical and differential ventilation. AB - Patients without respiratory symptoms were studied awake and during general anesthesia with mechanical ventilation prior to elective surgery. Ventilation perfusion (VA/Q) relationships, gas exchange and atelectasis formation were studied during five different conditions: 1) supine, awake; 2) supine during anesthesia with conventional mechanical ventilation (CV); 3) in the left lateral position during CV; 4) as 3) but with 10 cm of positive end-expiratory pressure (PEEP) and 5) as 3) but using differential ventilation with selective PEEP (DV + SPEEP) to the dependent lung. Atelectatic areas and increases of shunt blood flow and blood flow to regions with low VA/Q ratios appeared after induction of anesthesia and CV. With the patients in the lateral position, further VA/Q mismatch with a fall in PaO2 and increased dead space ventilation was observed. Atelectatic lung areas were still present, although the total atelectatic area was slightly decreased. Some of the effects caused by the lateral position could be counteracted by adding PEEP. Perfusion of regions with low VA/Q ratios and venous admixture were then diminished, while PaO2 was slightly increased; shunt blood flow and dead space ventilation were essentially unchanged. During CV + PEEP, there was a decrease in cardiac output, compared to CV in the lateral position. DV + SPEEP was more effective than CV + PEEP in decreasing shunt flow and increasing PaO2 in the lateral position; in addition to this, cardiac output was not affected. PMID- 2239114 TI - A new method for studying the ventilatory response in patients. AB - A method for clinical studies of the ventilatory response to carbon dioxide and to hypoxaemia in patients is described. The main parameters with this method are respiratory frequency, tidal volume, minute volume, timing, and drive. The ventilation of volunteers was not affected while breathing air through the designed apparatus. The response to carbon dioxide and to hypoxaemia in volunteers was reproducible and similar to what has previously been described. Our method proved suitable to test the ventilatory responses in patients with varying degrees of impaired ventilation-perfusion ratios and thus also in patients with a low PaO2. Our method has a higher accuracy than earlier methods. PMID- 2239116 TI - The effect of removal of cerebrospinal fluid on cephalad spread of spinal analgesia with 0.5% plain bupivacaine. AB - Increased intraabdominal pressure is well known to cause higher cephalad spread of spinal analgesia. The reason for this is believed to be a decrease in the cerebrospinal fluid (CSF) volume. If this mechanism is correct, then the cephalad spread of local anesthetic solutions should also be facilitated when the CSF volume is intentionally reduced without increasing the intraabdominal pressure. Sixty-six patients without evidence of increased intraabdominal pressure and undergoing urological procedures were randomly allocated to three groups. All received 10 mg 0.5% bupivacaine for spinal anesthesia. In Group I, the anesthetic was injected after free drops of CSF. In Groups II and III, three and five ml were removed, respectively, before injecting bupivacaine. Mean cephalad spread of analgesia 20 min after injection in the three groups was T10.2 +/- 2.0, T9.4 +/- 1.8 and T7.0 +/- 2.1, respectively. When CSF was reduced by 5 ml, the level of spread not only showed a statistically significant difference from that of the control group, but also from that of Group II (P less than 0.05). Our results show that higher cephalad spread of spinal anesthetic is possible by reducing the CSF volume without evidence of increased intraabdominal pressure. PMID- 2239115 TI - Intermittent high frequency ventilation. Clinical evaluation of a new mode of ventilation. AB - In this first clinical study of a new mode of ventilation, called intermittent high frequency ventilation (IHFV), a comparison was made in ten patients after myocardial revascularization, between normal ventilation, high frequency ventilation (HFV) and IHFV at 15, 60, 100 and 160 breaths per min (b.p.m.). During IHFV the ventilation was interrupted for 3 s 7 times per min. The measured mean trapped gas volumes were 219 ml at 60 b.p.m. and 716 ml at 160 b.p.m. At 160 b.p.m. during IHFV, the mean, mean airway pressures, pulmonary artery (PAP) and capillary wedge pressures and the Paco2 were decreased, while the cardiac output increased. When the Paco2 was maintained constant, IHFV also allowed a reduction in the mean peak and mean airway pressures. This new mode of ventilation can prevent sustained increases in the lung volume and provide a reduction in intrapulmonary pressures. It also permits the measurement of the trapped gas volume and end-tidal CO2 gas concentrations several times a minute for the clinical management of patients during high frequency ventilation. PMID- 2239117 TI - Position of minitracheostomy tube verified fiberoptically--a report of 2 cases. AB - Two reports concerning difficulties at insertion of a minitracheostomy cannula are presented. In one patient, a minitracheostomy tube perforated the posterior wall of the trachea, resulting in pneumomediastinum. In another patient, conventional signs, i.e. airflow and passing of a suction catheter through the cannula, were misleading in assessing the position of the tube. Fiberoptic tracheoscopy immediately after the performance of minitracheostomy revealed the position of the cannula in both cases. PMID- 2239118 TI - Disturbances in renal cortical perfusion with reference to the microsphere technique. AB - The microsphere technique for studying renal blood flow is based on injection of a small volume containing radioactively labelled microspheres into the left atrium, left ventricle or possibly the root of the aorta. In the present methodological study, superficial renal cortical blood flow and tissue oxygenation were measured in anaesthetized pigs by laser Doppler flowmetry and by oxygen surface electrode technique. Rapid and profound transient decreases in superficial renal cortical blood flow and tissue oxygenation were found after injection of small volumes of plasma and saline into the left atrium. This response was present also when solutions without microspheres were injected. The reaction was not abolished by careful adjustment of the injectate temperature. When the rapid onset of flow reduction is related to the estimated time of delivery of the bolus with microspheres, the validity of regional blood flow measurements using the microsphere technique within the superficial renal cortex must be seriously questioned. PMID- 2239119 TI - Continuous blockade of the lumbar plexus after knee surgery: a comparison of the plasma concentrations and analgesic effect of bupivacaine 0.250% and 0.125%. AB - In 20 patients a continuous block of the lumbar plexus was administered after knee-joint surgery, and the analgesic effect of two different concentrations of bupivacaine was compared. The same volume of bupivacaine was given to both groups of patients: a bolus dose of 0.4 ml/kg, 0.5% or 0.25%, followed by infusion of 0.14 ml/kg/h, 0.25% or 0.125%, respectively, via a catheter placed in the neurovascular fascial sheath of the femoral nerve according to the "3-in-1 block" technique. The median morphine consumption during the first 16 h postoperatively was 6.0 mg when bupivacaine 0.5/0.25% was used and 9.5 mg when 0.25/0.125% was used. This difference is not significant. The visual analogue pain scores were also similar in the two groups (P greater than 0.05). All plasma concentrations were below 4 micrograms/ml, the highest concentration measured being 3.6 micrograms/ml. It is concluded that when used for a continuous block of the lumbar plexus after knee-joint surgery, bupivacaine in a concentration of 0.125% offers the same pain relief as a concentration of 0.25%, and the risk of toxic reactions is reduced. PMID- 2239121 TI - Amrinone in perioperative low cardiac output syndrome. AB - Amrinone has been shown to have a beneficial effect on left ventricular function in low output syndrome (LOS), but its use after open-heart surgery has not been extensively revised. We studied 10 patients with LOS post-cardiopulmonary bypass (CPB), who failed to respond to conventional treatment (vasoactive drugs plus intraaortic balloon pump) and were treated with amrinone, 0.75 mg.kg-1 followed by a continuous infusion of 5 to 10 micrograms.kg-1-min-1. One patient failed to respond to the treatment and subsequently died, but in the other nine patients blood pressure and cardiac index increased, left filling pressure decreased and they were successfully weaned from the CBP and survived. These results suggest that amrinone, either alone or combined with other inotropic drugs and mechanical support, is a valuable drug in the management of LOS after CPB. PMID- 2239120 TI - Comparison of methohexital and pentobarbital for premedication in children. AB - Thirty children scheduled for elective orchiopexy or herniotomy were consecutively assigned at random to premedication with methohexital 80 mg/ml, 20 mg/kg rectally, 15 min before transportation to the operating room, or pentobarbital 28 mg/ml, 7 mg/kg rectally, 45 min before transportation. The quality of premedication was recorded at induction with halothane 1-2% and 60% N2O in O2 by mask. All patients received a caudal injection of bupivacaine 1.9 mg/ml, 1.25 ml/kg before surgery. Following completion of anaesthesia, the postoperative wake-up time and the duration of stay in the post-operative recovery room were recorded. The degree and quality of recovery were assessed using the Aldrete score every 30 min until discharge from the recovery room. The group of children receiving methohexital showed a highly significantly shorter awakening time, and a highly significantly shorter stay in the recovery room compared to the pentobarbital group. The children in both groups had a quiet, easy recovery without significant signs of confusion or agitation, and no difference in quality of recovery could be shown. Emergence delirium or agitation in connection with pentobarbital premedication and a possible relation to postoperative pain is discussed. PMID- 2239122 TI - The effects of incisional bupivacaine on postoperative narcotic requirements, oxygen saturation and length of stay in the post-anesthesia care unit. AB - We compared postoperative pain and narcotic requirements, oxygen saturation (SaO2) and length of stay in the post-anesthesia care unit (PACU) in patients who received 30 ml of either 0.25% bupivacaine (B) or saline placebo (S) infiltrated into the operative incision. Twenty ASA I-III patients undergoing abdominal surgery were studied in a double-blinded randomized prospective trial. Study and control groups were not different in patient age, procedure, intra-operative narcotics administered or preoperative SaO2. In the PACU, patients receiving B had significantly lower analog pain scores (6.0 vs 8.3, P = 0.02). They had lower respiratory rates (15.6 b/min vs 19.1, P = to 0.02), required significantly less narcotic (4.5 mg morphine sulphate vs 11.0, P = to 0.03) and were discharged from the PACU almost an hour sooner than patients receiving S (P = 0.02). Patients receiving B had significantly higher minimum SaO2 than those receiving S (93.3% vs 89.9, P = 0.04). Discharge pain scores, SaO2 and respiratory rates were not significantly different between B and S groups. Finally, mean requirements for narcotics for the first 24 h were reduced by approximately 30% (from 406.9 mg meperidine to 255.5 mg, P = 0.006). This study demonstrates that infiltration of a long-acting local anesthetic lowers initial pain scores and requirements for narcotics in the PACU. The effect can be seen for at least the first 24 h. A lower requirement for postoperative narcotics is accompanished by faster wake-up, more alert patients, and, most importantly, higher SaO2 and shorter PACU stay. This may have a significant effect on pulmonary morbidity following abdominal operations. PMID- 2239123 TI - Effects of epidural anesthesia on sympathetic nerve discharge to the skin. AB - Direct intraneural recordings of skin sympathetic activity (SSA) were performed to determine the magnitude of blockade of sympathetic fibers to the lower extremities during epidural anesthesia. Lumbar epidural catheters were inserted in nine volunteers. Multiunit postganglionic sympathetic activity was recorded in a skin fascicle of the peroneal nerve before and after injection of 4 ml of mepivacaine 2% epidurally, followed by an additional 12-16 ml after 5 min. Arousal stimuli such as sudden loud noises and noxious electrical skin stimulation were used to elicit transient sympathetic activation. Epidural anesthesia with upper level of sensory blockade at T4-T8 (n = 7) completely blocked spontaneous SSA and no detectable skin sympathetic activity could be provoked by arousal stimuli later than 14 min after the test dose. Sympathetic blockade was accompanied by marked increases in foot skin blood flow and loss of skin resistance responses to arousal. Epidural anesthesia with sensory blockade up to T10-11 (n = 2) only produced a partial sympathetic blockade. The result shows that epidural anesthesia with sensory blockade at T8 or above is equally as effective as injections of local anesthetics directly at postganglionic nerve fibers or ganglionic blockade in producing a complete sympathetic blockade of intraneurally recorded SSA. This neural blockade was paralleled by skin vasodilatation and a loss of sudomotor responses in the foot. PMID- 2239124 TI - The influence of 10 mg and 20 mg of bambuterol on the duration of succinylcholine induced neuromuscular blockade. AB - Bambuterol is an inactive prodrug which is enzymatically cleaved by plasma cholinesterase to yield the active compound, terbutaline. This catalytic process is accompanied by a selective inhibition of plasma-cholinesterase, the enzyme also necessary for the break-down of succinylcholine. We therefore studied the possible effect of bambuterol on succinylcholine-induced neuromuscular blockade in a double-blind fashion in patients undergoing surgery under general anaesthesia. Of the 39 patients studied, 13 patients had 10 mg of bambuterol, 12 had 20 mg and 14 were given placebo 10-16 h prior to anaesthesia. Succinylcholine 1 mg.kg-1 bw was administered after induction of anaesthesia. Following supramaximal train-of-four stimulation of the ulnar nerve, the tension developed in the adductor pollicis muscle was measured. Onset time and the durations of action (times to 10%, 25%, 75% and 90% recovery of the first twitch of the train of four response) were recorded. The mean recovery times were prolonged 30-50% in patients who had received 10 or 20 mg of bambuterol as compared with placebo. It is concluded that a prolonged duration of action of succinylcholine can be expected in patients being treated with bambuterol. PMID- 2239125 TI - Anaesthesia for resection of tumours in the trachea and central bronchi using the Nd-YAG-laser technique. AB - The use of lasers in upper airway surgery is now common practice. The introduction of the Nd-YAG laser technique makes it possible to perform endoscopic resection of tumours located in the trachea and central bronchi. Usually these patients require general anaesthesia. Our experience in 13 patients using total intravenous anaesthesia and jet ventilation with air is reported. Oxygen saturation was maintained at a higher level than when the patients were breathing 100% oxygen before anaesthesia. Occasional reductions in saturation were due to airway obstruction and were easily corrected by a short interruption of the procedure. All patients tolerated the anaesthesia and surgery well. No complications related to the anaesthetic method or the use of the Nd-YAG-laser occurred. A review of the possible hazards in these procedures is given together with advice on safety precautions needed. PMID- 2239126 TI - Long-term continuous axillary plexus blockade using 0.25% bupivacaine. A study of three cases. AB - Three patients, presenting with various traumatic, vasospastic and chronic neuromuscular disorders of the upper body, received continuous axillary block ranging from 4 to 16 days. Intermittent injections of 0.25% bupivacaine were used to provide analgesia, sympathetic blockade and muscle relaxation. No systemic or neurological side-effects were recorded. Nerve function recovered promptly after stopping the injections. It is concluded that continuous brachial plexus blockade is a clinically safe and effective technique for the relief of acute traumatic pain and vasospastic disorders of the upper limb. The technique, its merits and possible complications are discussed. PMID- 2239127 TI - Pronounced bradycardia after application of POR-8 (Ornipressin) under total intravenous anesthesia with propofol. PMID- 2239129 TI - Epidemiology of young strokes in rural Kashmir, India. AB - Kuthar valley in the Anantnag district of south Kashmir (North-west India) was surveyed to ascertain the prevalence of completed strokes. In a population of 63,645, the survey was from July to November 1986; 91 cases of completed stroke were detected giving a crude prevalence of 143/100,000. Only 10 (10.9%) cases (7W: 3M) were in the age group 15-39 years, a prevalence rate of 41/100,000. PMID- 2239128 TI - [A case of the anomalous intercostal, subcostal and lumbar arteries in man]. AB - This report describes an anomalous case of the multiple ipsilateral common trunk formation in the parietal arteries encountered during observed in the dissection of a 71 year-old Japanese female cadaver in the anatomical laboratory of Kanazawa Medical University. This subject had thirteen parietal arteries. Among the thirteen parietal arteries two arose from both the subclavian arteries (superior intercostal artery), and eleven arose from the descending aorta (aortic parietal arteries). Five arteries (R-1-R-5) were located on the right side, and eight (L-1 L-8) on the left. Of the eleven aortic parietal arteries, nine formed the ipsilateral common trunk, and the other two were independent branches (left 11th intercostal and 2nd lumbar arteries). The branching states of these parietal arteries were as follows: on the right side, R-1 was the common trunk for the 1st and 2nd intercostal arteries (the right superior intercostal artery), R-2 (was the common trunk) for the 3rd, 4th, 5th, 6th and 7th intercostal arteries, R-3 for the 8th and 9th intercostal arteries, R-4 for the 10th and 11th intercostal arteries and R-5 for the subcostal, 1st, 2nd, 3rd and 4th lumbar arteries. On the left side, L-1 was the common trunk for the 1st and 2nd intercostal arteries (the left superior intercostal artery), L-2 for the 3rd, 4th and 5th intercostal arteries, L-3 for the 6th and 7th intercostal arteries, L-4 for the 8th, 9th and 10th intercostal arteries, L-6 for the subcostal and 1st lumbar arteries, and L-8 for the 3rd and 4th lumbar arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239130 TI - Soluble class 1 antigens (sHLA) in CSF and serum of patients with HIV infection. AB - sHLA are secreted by B and T lymphocytes upon activation. These antigens are present in serum and cerebrospinal fluid (CSF). The establishment of a sHLA index, IH = (CSF sHLA/serum sHLA)/(CSF albumin/serum albumin) helped us to define that values above 9.7 reflect an intrathecal synthesis of these proteins. IH was significantly increased in a group of patients with intrathecal production of IgG against HIV-1 (HIV) and directly correlated with the synthesis of such antibodies. Therefore, IH seems to be an index of lymphocyte activation in CNS. PMID- 2239131 TI - Intermittent prophylaxis in febrile convulsions: diazepam or valproic acid? AB - In an open, prospective, randomized, and hospital-based study, comprising 219 consecutive children, 169 were given intermittent prophylaxis for one year, receiving either diazepam or valproic acid after their first febrile convulsion. Children admitted on odd dates (n = 89) were given rectal diazepam in solution every 12 h, whenever the temperature was 38.5 degrees C or more. Children admitted on even dates (n = 80) were given valproic acid as suppositories at times of fever. Twenty-three children in the diazepam group had a recurrence within 1 year versus 14 in the valproic acid group. On an intention-to-treat basis the 12-month recurrence rates in the 2 groups were similar, 27% vs 20%. The latter is well below figures for untreated controls from Denmark (32%), suggesting that intermittent valproic acid at times of fever may be effective, but further studies are needed. The number of complex recurrences, however, were significantly higher in the valproic acid group than in the diazepam group. Parental non-compliance was a major problem, and in the 2 study groups only 5 and 12 children, respectively, with recurrences were treated adequately. Sixty-nine children receiving diazepam had side-effects vs 37 receiving valproic acid. None were serious. PMID- 2239132 TI - Presence of plasma proteins in spinal nerve roots. An immunohistochemical study in the rat. AB - The presence of plasma proteins in the spinal nerve roots of normal rats was investigated using an avidin-biotin peroxidase technique on formaldehyde-fixed, paraffin-embedded material. Sections from the roots, exposed to a rabbit-anti rat albumin antiserum showed widespread, intense immunoreactivity which filled the spaces between the nerve fibers. The reaction product usually ended at the junction between the roots and the spinal cord. The sheath enclosing the roots showed the same strong immunoreaction. There was also a marked reaction in the dorsal root ganglia and peripheral nerve. Spinal cord sections, however, showed no extracellular reactivity, but many motor neurons of the ventral horn were distinctly positive, presumably the result of a normally occurring retrograde axonal transport from the periphery. Parallel sections from the roots exposed to rabbit anti rat IgG antiserum, rabbit anti rat IgM antiserum, rabbit anti human fibrinogen antiserum and rabbit anti human fibronectin antiserum revealed no positive immunoreaction. Thus, rat spinal nerve roots normally contain material with albumin antigenic properties. This would indicate that albumin is present in the extracellular fluid of the roots in the same way as in the endoneurium of peripheral nerves. The fluid microenvironment of the roots, therefore, appears to be different from that in the CNS which lacks extracellular albumin due to the impermeability of the blood-brain barrier. PMID- 2239133 TI - High-dose praziquantel for neurocysticercosis: serum and CSF concentrations. AB - Serum and CSF concentrations of praziquantel were analyzed in 8 patients with active neurocysticercosis aged 35 +/- 16 (mean +/- sd) years, in order to determine factors that may improve the therapeutic ratio. Praziquantel was given orally at 6-h intervals for 10 days at a daily dose of 100 mg/kg. Serum concentrations were determined at 1, 2 and 4 h, and CSF concentrations at 2 h after the morning dose. Peak serum concentrations occurred between 1 and 2 h after administration. There was a trend towards a drop in serum concentration from Days 1 through 5 to 10 of therapy. A fourfold increase in oral dose led to an eightfold rise in serum and CSF concentration, indicating saturation of hepatic metabolism. There were linear correlations (p less than 0.01) between serum and CSF concentrations of praziquantel, indicating free flow across the blood-brain barrier, above an apparent threshold, which may be related to occupation of plasma protein-binding sites. The results indicate that monitoring of serum concentrations may be clinically useful. PMID- 2239134 TI - A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain. AB - Antidepressant drugs are increasingly used in the management of chronic pain. They are mainly prescribed for cancer-related pain and central pain, e.g. phantom or stump pain, post-herpetic neuropathy. However, no controlled clinical trials have validated their in either pathology. Thus, physicians still do not know whether antidepressants are really effective and which might be best. It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself. To verify both the analgesic effect of tricyclic antidepressants, and the possible relationship between their antidepressant effect and the relief of central pain, we carried out a randomized, within-patient (cross-over) placebo controlled study in patients suffering from central pain. The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo (p less than 0.0001). Within the antidepressants tested, chlorimipramine, a blocker of serotonin reuptake, is significantly more effective (p less than 0.0001) than notriptyline, a blocker of noradrenaline reuptake. Finally, the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression. PMID- 2239135 TI - Computerized coordination ability testing. AB - Quantitative measurements of coordination ability were carried out on 76 women with a median age of 37, range 15 to 60. Spacing control, timing control and performance speed were recorded using newly developed computerized equipment, Catsys, presented in this paper. Twenty-three subjects were re-examined 2-3 months after the first measurements. A fair or even high degree of reproducibility of tests was found. Normal values for the entire group and correlation values for the re-examined group are presented. The results from this small study implies that the Catsys may be useful, e.g., in future clinical neurological practice of diagnostics and follow up on patients, in occupational medicine for detection of neurotoxic effects of various neurotoxic substances, in evaluation of drug effects and side effects and for testing people in occupations where normal coordination skills are absolutely necessary. PMID- 2239136 TI - Identification of IgG subclasses' oligoclonal bands in multiple sclerosis CSF. AB - IgG subclasses' oligoclonal bands in unconcentrated CSF from MS patients were detected by isoelectric focusing in agarose gel with subsequent immunoblotting using mouse monoclonal antibodies to human IgG subclasses and double-antibody avidin-biotin-alkaline phosphatase system. All MS CSF showed presence of oligoclonal bands specific to the IgG1 subclass; in addition, several of these samples also had oligoclonal bands specific to IgG3, IgG2, or IgG4, in order of decreasing frequency. Since the CSF of a greater number of MS patients showed oligoclonal bands specific to the IgG1 and IgG3 subclasses, the findings are consistent with those reported in patients with chronic viral infections and autoimmune diseases. PMID- 2239138 TI - Spinal arteriovenous malformations: neurological aspects and results of embolization. AB - Twenty consecutive patients with spinal arteriovenous malformations (AVMs) were found to have either a progressive, remitting or remitting-progressive course of disease. A characteristic progressive neurological decline was observed in 11 patients with dural fistulas and a similar decline was seen in 5 of the 9 patients with intradural AVMs. In addition to paraparesis and mixed sensory disorder, which ascended to a level of about T10, areas with spared sensation were occasionally found below this level. All cases with this progressive longitudinal myelopathy showed radiological evidence of a dilated medullary venous plexus. All patients were treated by embolization with only a low frequency of complications. Follow-up data verified a significant improvement of motor and sensory function, mainly during the first year after embolization. Cases with progressive neurological decline (dural and intradural AVMs) stopped deteriorating or improved and cases with a history of acute incidents (intradural AVMs) probably run less risk of acute deterioration. PMID- 2239137 TI - Red blood cell and adipose tissue fatty acids in mild inactive multiple sclerosis. AB - The fatty acid profiles of phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC) of the red blood cells of 30 patients with mild inactive multiple sclerosis (MS) and 30 healthy controls were studied by gas chromatography. The groups were well matched for factors likely to influence tissue lipid levels, including diet. The MS patients showed a significant reduction in PE eicosapentaenoic acid (p = 0.009) especially in women, and an increase in both PE dihomo-gamma-linolenic acid (p = 0.004) and PC stearic acid (p = 0.04). No reduction in linoleic acid was observed in either the PC or PE fractions of the MS subjects. A similar study of the fatty acid profile in adipose tissue in 26 MS and 35 healthy controls found no detectable eicosapentaenoic acid in either group. However, whereas docosahexaenoic acid was not detectable in any MS patient, 40% of the controls had measurable levels varying from to 0.1 to 0.3% of total estimated fatty acid (p = 0.0003). No reduction in linoleic acid in MS subjects was observed. Supplementation with oral fish body oil demonstrated that n-3 fatty acids were incorporated into red blood cells over 5 weeks and this occurred equally in MS and controls. The effects of oral supplementation on adipose tissue were studied after 1 and 2 years. Whereas many fatty acids such as linoleic acid were raised at 1 year, but did not rise subsequently, eicosapentaenoic acid and docosahexaenoic acid continued to rise through the 2 year period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239139 TI - Follow-up of antibiotically treated and untreated neuroborreliosis. AB - Follow-up of 57 patients who suffered from antibiotically untreated acute, monophasic neuroborreliosis 5 to 27 years ago shows no significant difference in comparison with the follow-up of 66 patients who suffered from antibiotically treated acute, monophasic neuroborreliosis during the last 5 years. In both groups, the involution of clinical symptoms and the normalization of pathological CSF findings were nearly identical. We found no significant difference of sequelae between the groups. Following acute neuroborreliosis, neither the antibiotically untreated nor the antibiotically treated patients developed chronic neuroborreliosis. Only in rare cases of primary chronic neuroborreliosis with CNS involvement did we observe convincing effects of antibiotics, which were given mostly in combination with glucocorticosteroids. PMID- 2239140 TI - Effect of methylprednisolone on motor function and spinal cord blood flow after spinal cord compression in rats. AB - The effect of methylprednisolone (MP) on neurologic recovery and spinal cord blood flow (SCBF) was investigated up to 4 days after a spinal cord compression injury in rats. The injury was produced at midthoracic level by applying a load of 35 g on a 2.2 x 5.0 mm compression plate for 5 min, which resulted in transient paraparesis. MP was given as a bolus dose of 30 mg/kg i.v. 60 min after injury (n = 20) and controls were given saline (n = 10). The motor performance was assessed daily as the capacity angle on the inclined plane and SCBF was measured by 14C-iodoantipyrine autoradiography on Days 1 or 4. On Day 1 the capacity angle was reduced from about 63 degrees preoperatively to 33 +/- 2 degrees (mean +/- SEM) in the control group and to 50 +/- 1 degrees in the group treated with MP (p less than 0.05). Thereafter there was a slight improvement in both groups, but the difference persisted throughout the observation period. On Day 4 both gray and white matter SCBF was better preserved in MP-treated animals than in the control group (59 +/- 4 versus 49 +/- 3 ml/min/100 g tissue for gray matter and 13.6 +/- 0.6 versus 10.7 +/- 0.8 ml/min/100 g tissue for white matter). Posttraumatic treatment with MP, thus, improved both the neurologic recovery during the first 4 days and SCBF as measured on Day 4. It is speculated that the effect of MP is at least partly exerted on the vascular bed. PMID- 2239141 TI - Long-term effect of ACTH treatment of relapse in multiple sclerosis. AB - A controlled, randomized study of the long-term effects of ACTH-treatment (100 units intramuscular, tapered over 12 weeks) of acute relapse in 29 MS patients was performed. Follow-up lasted one year. In some Kurtzke Functional System, the Ambulation Index and the Kurtzke Incapacity Scale a transient greater improvement in the ACTH-treated patients was observed. These superior results in the ACTH group were no longer present at 6 months. Significantly more side-effects were reported in the ACTH-group. After treatment with ACTH a higher, though not statistically significant, relapse rate in the following months was noticed. PMID- 2239142 TI - Seizures of unknown origin after the age of 50: vascular risk factors. AB - To investigate the possible etiologic factors of late onset seizures of unknown origin, 50 consecutive patients whose seizures started after age 50 and who had a normal CT, were screened. The seizures in this group were generalized in 70% and infrequent. The hypothesis that late-onset seizures of unknown origin were frequently due to microinfarcts, was evaluated by comparing the frequency of arterial hypertension, coronary heart disease, peripheral vascular disease, carotid bruits, diabetes mellitus and smoking in these patients with appropriate control groups. The results showed that the frequencies of these cardiovascular risk factors were similar to those of sex and age-matched controls and much lower than in a comparable series of patients whose seizures followed a stroke, or patients with stroke but not seizures. These data suggest that subclinical cerebrovascular disease is probably not a frequent etiology of late-onset epilepsy of unknown origin. The cause of these seizures remains to be elucidated. PMID- 2239143 TI - Conventional vs controlled-release carbamazepine: a multicentre, double-blind, cross-over study. AB - The tolerability and pharmacokinetics of a new controlled-release (CR) formulation of carbamazepine (CBZ), were assessed in a multicentre, double-blind, cross-over trial, carried out in 48 epileptic patients (21 men, 27 women; mean age 34.2 years) on conventional CBZ monotherapy, but without complete seizure control (n = 22) or with intermittent side effects (n = 4), or with both (n = 22). Eligible patients were randomized to conventional CBZ or CR CBZ, each given in sequence at individualized daily doses, subdivided into the lowest number of administrations. Each period of the cross-over consisted of a first phase of optimal dose finding (lasting up to two months) and a second one of maintenance (lasting one month) used for evaluation. At the end of each period, a 10-h plasma CBZ and CBZ-epoxide concentration profile, as well as the tolerability and the efficacy of the drugs, were evaluated. The mean CBZ daily dose increased by 16% during the administration of the CR formulation. Fluctuations of total CBZ and 10, 11-epoxide plasma level daily profiles at steady-state were significantly (p less than 0.001) lower during CR CBZ treatment, leading to a significant (p less than 0.001) decrease in intermittent side effects (6 patients on CR CBZ vs 26 on conventional CBZ). Finally, 38 patients on CR CBZ (vs 15 patients on conventional CBZ) were treated with a b.i.d. regimen. PMID- 2239144 TI - A computer-aided technique for testing cognitive functions. Validated on a sample of Danes 30 to 60 years of age. AB - With the growing importance of occupational behavioural neurotoxicology the demand for a standardized and reliable cognitive test battery has become urgent. The present study deals with the compilation of a test battery, the purpose of which is to be sensitive to mild brain dysfunction and suitable for modern microcomputer administration and scoring. The battery comprises tests of learning and memory functions specific for each brain hemisphere (Face Recognition Test and Number Learning Test), visuomotor function separately for continuous and discrete tasks (Figure Drawing Test and Pen-to-Point Test), visuospatial function (Parallelogram Test), visual and auditive perception, attention and vigilance (Bourdon-Wiersma Test and Continuous Reaction-Time Test), and concentration (Continuous Graphics Test). The complete test battery was administered and scored on a slightly modified Tektronix 4052 computer with a Tektronix 4956 digitizer as a peripheral device. The validity of the battery was analysed on the basis of a sample of the normal Danish population (N = 1262) stratified for the ages 30, 40, 50, and 60 years, the two sexes, and residence in one of 11 municipalities in the western part of Copenhagen County. Using a 16-dimensional multivariate model comprising biological, social, psychological, and environmental factors, and also examiner behaviour, statistical analyses confirmed hypotheses of influence by the factors Age, Sex, Schooling, and Social Group, i.e. these factors partially explained the variance in the case of almost all the test parameters. Moreover, psychic stress, as determined in a questionnaire, had explanatory power with tests demanding attention and concentration. Hypotheses of effects on test performance by Smoking Status and psychophysiological diurnal or annual rhythms, i.e. Time of Day, and Time of Year, were confirmed for a few parameters, but the effects differed to some extent from those described in the literature. Alcohol Consumption, Drug Consumption Affecting the CNS, Cardiovascular Diseases or Disorders, Metabolic Diseases or Disorders, CNS Injuries or Disorders, and Occupational Activity Status, all revealed by questionnaire, were not found to show the assumed significant effects on test performance. However, a hypothesis of an effect originating in differences between different examiners' behaviour was confirmed for a number of test parameters, although all the test measurements and scorings were done automatically by computer. On the basis of a re examination of 19 patients previously diagnosed as suffering from diffuse organic psychosyndrome, the sensitivity of the test battery was estimated to be 0.79. The specificity was estimated to be 0.79 on the basis of the results of the original sample.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2239145 TI - Morphometric studies on the human sural nerve. PMID- 2239147 TI - The behavior of the extracellular matrix and the basal lamina during the repair of cryogenic injury in the adult rat cerebral cortex. AB - A well-defined coagulative lesion was produced in the fronto-parietal cortex of adult rats by application of a cold probe, and the chronological sequence of events during the healing process, particularly the relationship between astroglial processes and the newly forming basal lamina (BL) and the behavior of the extracellular matrix (ECM) was examined immunocytochemically and ultrastructurally. By electron microscopy, new BL synthesis was first noted 7 days following injury, and a continuous and well-defined BL was present from 14 days onward. These findings correlated well with the pattern of immunoreactivity for laminin and for type IV collagen. Both laminin and type IV collagen appeared both to be produced primarily by mesenchymal cells within and around the wound as well as those of the blood vessels, and to become an integral part of the new BL. Although there was no immunocytochemical evidence to indicate secretion of laminin, type IV collagen or fibronectin by astrocytes, a well-defined BL appeared to form only in tight apposition with astroglial processes over the pial surface. This suggests that the BL is formed by subpial astrocytes in close interaction with ECM components at the pial surface. Fibronectin appears to contribute significantly to the formation of the BL by providing a suitable substratum for the coordinated cellular interaction necessary for successful regeneration of the BL. PMID- 2239146 TI - Tumors of the meninges: proposed modifications of the World Health Organization classification. AB - The present WHO classification of meningiomas has served us well. In keeping with the adage, "if it ain't broke, don't fix it," alterations should be made with due caution. These proposed modifications of the WHO classification are prompted by advances in our understanding of the pathobiology of meningeal neoplasms, as well as a need for an orderly scheme based upon factors of clinical importance. The author is well aware, that given the vastly differing technologies available to those utilizing the "blue book," its application must have a basis in routine histology rather than in "high-tech" procedures. No classification is ideal, but the modifications suggested represent a compromise between the pathologist's need for a complete morphologic exposition and the clinician's desire for a concise classification of therapeutic and prognostic significance. PMID- 2239148 TI - Alzheimer neuropathology in non-Down's syndrome mentally retarded adults. AB - We examined the brains of 385 mentally retarded adults aged 23-90 years without Down's syndrome (DS), metabolic disorder, or hydrocephalus to extend our knowledge about the occurrence of Alzheimer-type neuropathology in this population. Relevant measures of neuropathology also were related to selected information available from clinical records. The presence of one or more neurofibrillary tangles (NFT) and/or neuritic plaques (NP) was observed in 63.4% of all cases and varied with age. The prevalence of positive cases was higher when mental retardation was due to head trauma, congenital malformation, or familial factors and when a history of seizures was reported. Comprehensive morphometric analyses of neocortical, hippocampal and parahippocampal areas indicated that recommended age-specific quantitative criteria for the diagnosis of Alzheimer disease [Khachaturian ZS (1985) Arch Neurol 42:1097-1105] were met in 9.5% of cases less than 50 years of age, 54.2% between 50 and 65, 70% between 66 and 75, and 87% of the cases greater than 75 years of age. However, a limited immunohistochemical study revealed that in most cases the NP did not have a neuritic component containing paired helical filaments and in this respect most of the plaques observed in this population may differ from those most strongly associated with Alzheimer disease. In addition, substantial numbers of NFT were seen in frontal cortex, contrasting with results reported in the literature for nonretarded populations. The number of NP per mm2 consistently increased with age for all areas examined, while the relationship between NFT density and age varied across areas, and was clearly not monotonic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239149 TI - Ultrastructure of the neuropil threads in the Alzheimer brain: their dendritic origin and accumulation in the senile plaques. AB - Thread-like structures immunoreactive with paired helical filaments and tau antisera were demonstrated as mesh-works in the neocortices of five brains with Alzheimer-type dementia, but not in those of five normal aged control brains. The ultrastructure of the threads was examined using paired routine electron microscopic ultrathin sections and adjacent 0.4-micron-thick semithin sections, immunostained for beta protein. Outside the beta protein-positive senile plaques, neuropil threads appeared sporadically as small slender neurites, containing either regularly constricted or straight filaments. These neurites often showed dendritic profiles. Similar threads were also seen within the senile plaques. The threads were accumulated in amyloid fibril-rich primitive plaques, but not in amyloid fibril-poor diffuse plaques. The presence of these threads was closely associated with neurofibrillary tangle formation. Our findings suggest that wide spread change of the neuropil neurites, neuropil threads or curly fibers, both outside and inside of the senile plaques are dendritic in origin and play an important role in the clinical manifestation of dementia. PMID- 2239152 TI - Effect of denervation on regenerating muscle plasma membrane integrity: freeze fracture and dystrophin immunostaining analyses. AB - We investigated time sequentially, the densities of intramembranous assembly "orthogonal arrays" of regenerating rat extensor digitorum longus muscle after bupivacaine-induced muscle injury. There was no evidence of orthogonal arrays at the early stage, but the densities of orthogonal arrays increased with the maturation of the innervated regenerating myofibers. In contrast, the orthogonal arrays were scarcely observed at any time point examined in denervated regenerating muscles. Therefore, the neural factor may have an important effect on the appearance of orthogonal arrays. Moreover, we studied the immunostainability of Duchenne muscular dystrophy gene product "dystrophin" in the regenerating muscle at the same time points. Positive immunostaining was observed in both innervated and denervated regenerating myofibers even from the early stage of regeneration. On the basis of these data, the relationship between orthogonal array and dystrophin are discussed. PMID- 2239150 TI - Amyloid in the brains of aged squirrel monkeys. AB - In this immunocytochemical study, the brains of nine squirrel monkeys (Saimiri sciureus), ranging from 8 to 27 years of age, were examined for the presence and distribution of beta/A4 amyloid, a 4-kilodalton peptide. In aged squirrel monkeys, amyloid is associated primarily with intracerebral and meningeal capillaries and arterioles and occurs to a lesser degree as small and/or diffuse deposits in the neural parenchyma and in the dense cores of senile plaques. Cerebrovascular amyloid is found primarily in neocortex, amygdala, and septum verum and is rare or nonexistent in other subcortical gray structures, white matter, cerebellum, and spinal cord; this pattern of localization is comparable to that in humans with cerebral amyloid angiopathy. There is a significant correlation between cerebrovascular and parenchymal deposits of amyloid. However, cerebrovascular amyloid is always the most abundant form in squirrel monkeys, even in cases of severe cerebral amyloidosis. In contrast to squirrel monkeys, aged rhesus monkeys (Macaca mulatta) develop mostly parenchymal deposits of amyloid and have relatively less vascular amyloid. This species difference in the histological distribution of amyloid suggests that separate mechanisms may influence the accumulation of amyloid in cerebral blood vessels and in the neural parenchyma. These data also indicate that the squirrel monkey can serve as a model for investigations of cerebrovascular amyloidosis. PMID- 2239151 TI - Morphology and distribution of HIV-1 gp41-positive microglia in subacute AIDS encephalitis. Pattern of involvement resembling a multisystem degeneration. AB - Among 100 brains from patients with acquired immunodeficiency syndrome (AIDS), 33 brains (21 adults and 12 children) with histological evidence of subacute AIDS encephalitis were immunostained with one of the most sensitive antibodies to HIV 1 antigen, anti-gp41. Twenty-six (20/21 adults, 6/12 children) of the 33 brains showed pg41 positivity. Brains from children had fewer gp41-positive cells than brains from adults. The distribution of gp41-positive cells was characteristic. They were frequently detected and most numerous in the globus pallidus (medial greater than lateral). Although gp41-positive cells were prevalent, fewer were detected in the corpus striatum and thalamus. Of infratentorial areas involved, the ventral midbrain, especially the substantia nigra, and the dentate nucleus contained many positive cells. Lower levels of infections, often patchy, were noted in the cerebral and cerebellar white matter and pontine base. Gp41-positive cells were rarely seen in the cerebral cortex, medulla, spinal cord, leptomeninges, choroid plexus, ependyma, subependymal areas and endothelia. Besides immunoreactive macrophages and multinucleated cells, gp41-positive microglia with various morphological alterations were abundant in the deep cerebral gray matter, ventral midbrain and dentate nucleus. Most of these microglia were undetectable with conventional histological methods. We discuss the significance of the distribution of HIV-1-infected cells, especially microglia, with respect to cellular tropism and involvement of deep gray matter nuclei in a pattern reminiscent of a multisystem atrophy. PMID- 2239153 TI - Anti-macrophage CR3 antibody blocks myelin phagocytosis by macrophages in vitro. AB - Myelin phagocytosis in Wallerian degeneration of peripheral nerves depends on invasion of nerves by non-resident macrophages. The present study was done to clarify the role of the macrophage complement receptor type 3 (CR3) in myelin removal. Myelin phagocytic capacity of invading macrophages was abolished by treatment of cultured nerves and macrophages with anti-CR3 antibody or by serum complement depletion with cobra venom factor. This indicates that myelin phagocytosis is mediated by the macrophage CR3. PMID- 2239155 TI - Skeletal muscle changes associated with equine myotonic dystrophy. AB - A progressive neuromuscular disorder in young horses, clinically apparent as early as 1 month of age, is characterized by generalized myotonia, muscle stiffness, muscle weakness and atrophy. Myotonia is identified by percussion dimpling and myotonic EMG discharges. Changes in one case included testicular hypoplasia, cataract formation, and glucose intolerance, indicating a systemic involvement. Pathologic changes in skeletal muscles from three affected foals were examined. Sarcoplasmic masses, ringed fibers, internal positioning of sarcolemmal nuclei, and nuclear rowing were among the primary histologic changes noted. Variation in fiber diameter size, especially atrophy, and type I predominance were also prominent changes. A neurogenic involvement was indicated by type grouping changes in several muscles. PMID- 2239154 TI - Expression of monoamine oxidase B activity in astrocytes of senile plaques. AB - Monoamine oxidase (MAO) histochemistry has been performed in brains from patients with dementia of Alzheimer type (DAT) and aged controls. Conspicuous MAO-positive cell clusters were frequently observed in the amygdala, hippocampus, and insular cortex in the brains of DAT. Double staining with glial fibrillary acidic protein immunohistochemistry revealed that the cluster-forming MAO-positive cells were astrocytes. Using Bielschowsky's method, Congo red and thioflavin S counterstaining, this astrocytic mass was shown to be associated with senile plaques. By the enzyme inhibition experiment, MAO activity in senile plaques was revealed to be of type B. The present results clearly indicate that MAO-B activity is expressed in fibrillary astrocytes in or around senile plaques, suggesting that these astrocytes metabolize exogenous amines in senile plaques. PMID- 2239156 TI - The early effects of methylmercury on the developing rat brain. AB - The effects of organic mercury compounds on the development of the brain are well known since the exposure of people at a large scale to methylmercury in the Minamata Bay area and in Iraq. The neuropathological examination of the brains of children prenatally exposed revealed dysplasia of the cerebral and cerebellar cortex, neuronal ectopia and several other developmental disturbances. In this experimental study we examined developmental mechanisms involved in methylmercury induced cerebral anomalies. By examining the fetuses soon after treatment we concentrated in the initial effects of the treatment. The pregnant rats were given 10 mg/kg methylmercury chloride i.p. on day 18. Already at 2 h after administration mitochondrial degeneration occurred in the endothelium of the cerebral capillaries. Subsequently hemorrhages developed interfering with the cellular arrangement in the ventricular zone, with neuronal migration in the intermediate zone and with the development of the cortical cytoarchitecture. Macrophages and cavities appeared in the hemorrhagic areas. It is suggested that the abnormalities seen in the experiments can be considered as the initial methylmercury-induced effects which, in combination with various other toxic effects, ultimately result in the anomalies that have been observed in the brains of children prenatally exposed to methylmercury. PMID- 2239157 TI - Lauge-Hansen classification of malleolar fractures. An assessment of the reproducibility in 118 cases. AB - The radiographs of malleolar fractures in 118 consecutive patients were assessed by 4 observers using the Lauge-Hansen classification. The interobserver variation was large; only 51 of the 118 radiographs were classified identically by all 4 observers. With the purpose of assessing intraobserver variation, the same observers classified the same radiographs 6 weeks later. The first and the second classification were identical in 75-97 of 118 radiographs (64-82 percent). These results show that the Lauge-Hansen system is difficult to apply in a reproducible way. PMID- 2239158 TI - Ankle instability caused by prolonged peroneal reaction time. AB - The reaction of 15 functionally unstable ankles to sudden inversion was described by monitoring muscle activity, joint motion, and alternation of the body center of pressure. The results were compared with those of 15 stable controls. Stable and unstable subjects showed a similar reaction pattern to sudden inversion: first, a peripheral reflex action, namely, a contraction of the peronei counteracting the ankle inverting momentum, and, then, a centrally elicited pattern, namely, a flexion of the hip, knee, and ankle relieving the vertical pressure on the ankle and producing ankle eversion. Unstable subjects did not show a defect in their central processing of afferent input. In contrast, a prolonged reaction time (median 84 msec compared with 69 msec in stable subjects) suggested a partial deafferentation of the reflex stabilization of the ankle and substantiated the theory of a proprioceptive deficit being responsible for ankle instability. PMID- 2239159 TI - Anterior stabilization of pathologic dens fractures. AB - By an anterior approach, six pathologic dens fractures were stabilized with screws and methyl methacrylate cement. All the patients had immediate pain relief and could be mobilized without external support. Using the anterior approach, the tumor can be removed and the instability neutralized at the site of the lesion. PMID- 2239160 TI - Chronic trapezius myalgia. Morphology and blood flow studied in 17 patients. AB - Bilateral open biopsies from the painful upper part of the trapezius muscle were studied in 17 patients with localized chronic myalgia related to static load during repetitive assembly work. Isolated pathologic ragged red fibers were related to the presence of myalgia. The phenomenon indicating disturbed mitochondrial function was confined to the Type 1 fibers. Using a laser-Doppler flowmeter, the muscle blood flow was recorded in the exposed muscle before a biopsy was taken. Pain was assessed and graded as the difference between the two sides, as was the presence of ragged red fibers. The myalgia correlated with reduced local blood flow: the greater the pain difference, the greater the reduction in blood flow. There was a correlation between the presence of mitochondrial changes and reduced muscle blood flow. PMID- 2239161 TI - Microsurgery versus standard removal of the herniated lumbar disc. A 3-year comparison in 150 cases. AB - The outcome of 150 patients with herniated lumbar disc treated by either microsurgical or standard discectomy were retrospectively reviewed after an average of 3 years. Both techniques provided satisfactory results, with 85 percent good or excellent outcome. Microsurgery gave less intraoperative bleeding, shorter hospitalization, and more rapid return to work. The main drawback was a higher recurrence rate of disc prolapse. PMID- 2239162 TI - Function and social status 10 years after hip fracture. Prospective follow-up of 103 patients. AB - Function and social outcome for 103 consecutive patients, mean age 75 years, admitted from their own homes after a hip fracture were studied during a 10-year period. Within 4 months after the fracture, 81 patients had returned home, and the percentage of survivors living at home from then on was then fairly constant. At 10 years after fracture, 31 patients were living at home, 6 were in institutions, and 66 were dead. ADL, walking ability, and household activities remained at the level already achieved within 4 months after fracture during the 10-year period. The need for social services help did not increase; about one third of the survivors had communal home help throughout the 10-year period. Patients who before fracture were healthy and living with someone and within 2 weeks after the fracture could walk with a four-legged aid or better had a good prognosis for living in their own home. The hip fracture did not effect their subsequent fate. PMID- 2239163 TI - Internal fixation of 410 cervical hip fractures. A randomized comparison of a single nail versus two hook-pins. AB - Totally, 410 patients with a cervical hip fracture were randomized between two methods of osteosynthesis: a single nail (Rydell) and two hook-pins (LIH). Seventy-five percent of the patients were women. Sixty-nine percent were alive after 2 years. The patients were followed up with clinical and radiographic examinations for 2 years postoperatively. No difference between the two groups were found regarding quality of reduction, early displacement within 3 months, extraction after healing, nonunion, late segmental collapse, or reoperation with a total hip arthroplasty. Nor did we find any differences between the two groups when selecting those alive after 2 years or when dividing the fractures in displaced and nondisplaced fractures. PMID- 2239164 TI - Fixation of femoral neck fractures. A four-flanged nail versus threaded pins in 200 cases. AB - Two methods of internal fixation for cervical hip fractures were compared in a "randomized to surgeons" type of study. One hundred patients were treated with the Rydell four-flanged nail and 100 with the Gouffon pins. Redisplacement, nonunion, or segmental collapse occurred in 27 patients operated on with the Rydell nail and in 29 patients operated on with the Gouffon pins. According to the actuarial method of follow-up, the failure rates after 2 years were 31 and 33 percent in the two groups. PMID- 2239165 TI - Hip physiolysis. Bilaterality in 62 cases followed for 20 years. AB - The frequency of bilateral physiolysis colli femoris was evaluated in 62 patients. At first admission, 5 patients had a bilateral slipping. Further, 9 patients had slipping diagnosed in the contralateral hip during adolescence 1-3 years after the primary operation. At the follow-up examination 22 years after the primary operation, radiographs showed bilateral sequelae of slipping in 30 of 62 patients. Of the nine slips diagnosed later during adolescence, one showed mild and two severe arthrosis. Among the 16 slips diagnosed at follow-up, mild arthrosis was found in four hips. We recommend bilateral pinning at first admission in all patients with a slipped capital femoral epiphysis. PMID- 2239166 TI - Age-related changes in femoral trabecular bone in arthrosis. AB - Age-related changes in the cancellous bone in selected regions of the proximal femur and iliac crest were assessed. An arthrosis group and a control cadaver group, partitioned into subjects younger and older than aged 50 years, were compared. The control group comprised 69 heads of femur and iliac crest samples. The arthrosis group comprised 28 consecutive heads of femur affected by primary arthrosis and an iliac crest biopsy taken during hip arthroplasty. Cancellous bone was sampled from four selected regions in the proximal femur. Histomorphometric estimates of percentage bone volume were determined using image analysis. In the young controls the bone volume was higher than that in the old controls for all the regions. In the arthrosis group the bone volume was higher than that of the old controls except for the subchondral principal tensile and medial to the greater trochanter regions. The old controls had regression of bone volume on age for the subchondral and medial principal compressive regions and the iliac crest. The arthrosis group had a minimal dependence of bone volume on age. Our study showed that primary arthrosis modulates the age dependence of bone volume in the proximal femur. PMID- 2239167 TI - Indomethacin influences Moloney's sarcoma and associated periosteal osteogenesis in the mouse. AB - The effect of indomethacin on periosteal osteogenesis mediated by the Moloney sarcoma virus was studied using a mouse model. In the indomethacin-treated animals, the development of sarcoma was inhibited, as evaluated by the tumor incidence, tumor size, and maximal tumor duration. Periosteal osteogenesis mediated by this sarcoma was lower than in saline-treated control mice. PMID- 2239168 TI - Epidemiology of meniscal lesions in the knee. 1,215 open operations in Copenhagen 1982-84. AB - In a suburban area of Copenhagen with approximately 620,000 inhabitants, all the openly operated on meniscal lesions of the knee joint between 1982 and 1984 inclusive were reviewed. The mean annual incidence of meniscal lesions per 10,000 inhabitants was 9.0 in males and 4.2 in females. The highest incidences were seen in the 3rd, 4th, and 5th decades of life. A higher frequency of trauma related to onset of symptoms was found among males (77 percent) than among females (64 percent). The bucket-handle lesion was the most frequent type of meniscal lesion in males (35 percent), whereas peripheral detachment was the most frequent in females (41 percent). A variable frequency of trauma inducing the lesions in males and females did not explain differences in type of meniscal lesion. Nineteen percent of our 1,215 patients had a partial meniscectomy, whereas 0.7 percent had meniscal repair. PMID- 2239169 TI - Scintigraphy in the assessment of anterior knee pain. AB - Sixty knees presenting with chronic anterior pain were investigated. A diffusely increased uptake indicated sympathetically mediated pain provided other diagnoses such as synovitis or widespread arthrosis were excluded. Focal uptake was not specific to any one condition, but could occur in chondromalacia patellae or recent dislocations. However, the commonest appearance found in chondromalacia patellae was a normal scan. A characteristic scintigraphic appearance in symptomatic postpatellectomy knees, which has not been previously reported, was increased uptake in the femoral groove. In all the cases where no clinical or arthroscopic diagnosis was made, the bone scan was normal. The use of radioisotope scintigraphy is recommended in the problem knee presenting with anterior pain. PMID- 2239171 TI - Proximal row carpectomy in perilunate dislocations and lunatomalacia. AB - Proximal row carpectomy was performed in 13 wrists with old unreduced perilunate dislocations and in 4 wrists with Kienbock's disease. One failure was converted to wrist arthrodesis, and 2 patients were lost to follow-up. The remaining 14 patients were reexamined after 11 (3-19) years. Average ranges of wrist motion were 37 degrees of dorsiflexion, 30 degrees of palmar flexion, 5 degrees of radial deviation, and 24 degrees of ulnar deviation. Grip strength averaged two thirds of the uninvolved hand. Pain relief was achieved in 12 patients, who all returned to their previous occupations. The results according to Cooney's criteria were 1 good, 8 fair, and 5 poor. PMID- 2239170 TI - Effect of glycosaminoglycan polysulfate on chondromalacia patellae. A placebo controlled 1-year study. AB - The effect of glycosaminoglycan polysulfate (GAGPS) on damaged patellar cartilage and clinical symptoms of chondromalacia was studied on 31 patients in a placebo controlled double-blind trial. The clinical diagnosis was confirmed by arthroscopy. The treatment consisted of 12 intramuscular injections of either GAGPS or placebo, and the patients were followed for 1 year. In 26 patients, rearthroscopy was performed at the 1-year follow-up. Comparison of the two arthroscopies showed improvement in 8/13 patients in the GAGPS group compared with 3/13 in the placebo group. The clinical parameters correlated well with the results of the arthroscopies. The results support the use of GAGPS for chondromalacia patellae. PMID- 2239172 TI - Cast or external fixation for fracture of the distal radius. A prospective study of 126 cases. AB - In a prospective 4-year study, 126 consecutive patients with a fracture of the distal radius were followed. Functional, anatomic, and radiographic final results of fixation with above-the-elbow cast immobilization were compared with the results obtained with external fixation. The results following external fixation of comminuted intraarticular fractures were better than those of similar fractures treated in a cast. Aged osteoporotic patients tolerated better residual deformities, and the clinical results had a relatively low correlation with the final anatomic alignment. We suggest that extraarticular fractures of the distal radius should be treated with cast immobilization. Comminuted intraarticular fractures of the distal radius should be treated with external fixation, which maintains accurate anatomic position until solid fracture healing is achieved. PMID- 2239173 TI - Epidemiology of distal radius fractures in Iceland in 1985. AB - Between March 1985 and March 1986, 249 fractures of the distal radius in patients over 15 years of age were treated in the Reykjavik area, which had a total at risk population of 100,154. The incidence pattern was similar to what has been reported in recent Nordic studies except that the fracture risk of women was lower than in Oslo in 1979 and Malmo in 1980-81, and for men higher than in Fredriksborg in 1981. Fifty-seven percent of the patients had employment at the time of accident. The majority of accidents happened outdoors, especially on sidewalks and in streets, and were more common during the winter months. PMID- 2239174 TI - Short-term cefotaxime prophylaxis reduces the failure rate in lower limb amputations. AB - The effect of prophylaxis with a broad-spectrum antibiotic agent in lower limb amputations was studied in a prospective, randomized investigation of 38 patients. Nineteen received cefotaxime (Claforan) and 19 served as controls. Three patients died in the immediate post-operative period. In the treatment group, 15/18 healed compared with 10/17 controls (P less than 0.001). We concluded that short-term cefotaxime prophylaxis increases the chances to achieve good stump healing. PMID- 2239176 TI - Late pulmonary metastases from chondroblastoma of the distal femur. A case report. AB - A patient treated with curettage and bone grafting for a chondroblastoma of the distal femur sustained a pathologic fracture after a local recurrence. He then underwent a local, radical resection and an arthrodesis of the knee. Ten years after the first operation, pulmonary metastases were found, for which he underwent a metastasectomy (thoracotomy). At the latest follow-up, 1 year later there were no signs of tumor. PMID- 2239175 TI - Coccygodynia treated by resection of the coccyx. AB - Sixty-five patients suffering from coccygodynia resistant to conservative treatment had total or partial coccygectomy, all without serious complications. Eight reoperations were performed. After an average of 15 years, 46 of the 55 patients seen at follow-up were satisfied. A normal radiograph of the coccyx does not exclude a good result from coccygectomy. We recommend total coccygectomy using a longitudinal incision in carefully selected and well-informed patients. PMID- 2239177 TI - Distal tibial osteochondroma deforming the fibula. AB - Three children had osteochondromata in the lateral part of the distal metaphysis of the tibia causing impingement with erosion and deformity of the fibula. The osteochondromata were removed through an anterior approach without osteotomy of the fibula. At reexamination 1.5-11 years postoperatively, the patients had normal ankle function. Remodeling of the fibula had gradually occurred in all the cases, most in the youngest patient. There was no injury to the distal tibial physis. PMID- 2239178 TI - Fracture dislocation of the ankle with the fibula trapped behind the tibia. A case report. AB - The authors present a case of fracture dislocation of the ankle with the fibula entrapped behind the tibia--Bosworth's fracture. It is often unrecognized as such because it is so rare and because radiographs are not correctly interpreted. A stable reduction can be obtained by closed treatment when promptly recognized. PMID- 2239179 TI - First Scandinavian-Japanese Shoulder Meeting. Helsinki, Finland, June 26-29, 1989. Abstracts. PMID- 2239180 TI - Danish Orthopedic Society. Copenhagen, October 27-28, 1989. Abstracts. PMID- 2239182 TI - The Netherlands Orthopedic Society. Utrecht, January 18-19, 1990. Abstracts. PMID- 2239181 TI - Norwegian Orthopedic Society. Oslo, October 27-28, 1989. Abstracts. PMID- 2239183 TI - Finnish Orthopedic Association. Kuusamo, April 23-27, 1990. Abstracts. PMID- 2239185 TI - Finnish Orthopedic Association. Mariehamn, May 11-12, 1990. Abstracts. PMID- 2239184 TI - Danish Orthopedic Society. Helsingor, May 4-5, 1990. Abstracts. PMID- 2239186 TI - The Netherlands Orthopedic Society. Soest, May 12, 1990. Abstracts. PMID- 2239187 TI - The Swedish Orthopedic Society. Kalmar, September 5-7, 1990. Abstracts. PMID- 2239188 TI - [Magnetic resonance imaging in knee injuries]. AB - Of all the diagnostic imaging techniques for the injured knee, Magnetic Resonance Imaging (MRI) has been shown the most worthwhile. Indications for standard X rays, arthrography and ultrasonography are briefly reviewed. Advantages of MRI, the technical aspects and the sequences used are explained. After a short description of the signals of all the common anatomic components of the knee, we describe MR findings in meniscal pathology, tenoligamentous lesions and cartilage and bone injuries. PMID- 2239189 TI - Internal fixation of tibial plateau fractures using the AO instrumentation. AB - Between January 1970 and December 1985, 76 patients (76 fractures) underwent internal fixation for tibial-plateau fractures as recommended by the AO-group (14). Fifty patients were available for follow-up. The long term results of this retrospective study are reported. Subjective results were satisfying. Forty-four percent of the patients were painfree and only 8% had severe postoperative pain, which was clearly related to osteoarthritis. Eight-eight percent of patients had no instability at follow-up. Clinical and radiographic results were evaluated for mobility, laxity and osteoarthritis. Thirty-five patients had a loss of flexion averaging 16.6 degrees. In 12 patients the average decrease in extension amounted to 7.5 degrees. Valgus increase averaged 9.7 degrees in 17 patients, and the average varus increase was 7.5 degrees in 4 patients. Seventy-four percent of patients showed no laxity at follow-up. The finding of osteoarthritis on X-ray was well correlated with the postoperative incongruence of the articular surface. It was also found to develop earlier in patients who underwent (partial) meniscectomy. Some general considerations about tibial condyles fractures are presented, and the technique used by the authors is discussed at length. The indications for internal fixation are also evaluated. The importance of adequate reduction, stable internal fixation and vigorous postoperative rehabilitation is stressed. PMID- 2239190 TI - About radioactivity in some PMMA bone cements. AB - Various bone cements containing zirconium oxide (ZrO2) as X-ray contrast medium were tested for radioactivity by means of a gamma spectrometer. All measured bone cements (PALACOS, IMPLAST, SULFIX-6) showed a certain degree of radioactivity. The radiation source in the bone cement is the added zirconium oxide, which is polluted by radioactive elements. As these X-ray contrast media remain in the body for decades as components of the bone cement, the radioactive zirconium oxides should be substituted by high purity radiation-free zirconium oxide or barium sulfate. PMID- 2239192 TI - Shoulder instability in Ehlers-Danlos syndrome. An indication for surgical treatment? AB - In a 19-year-old female patient with Ehlers-Danlos Syndrome and bilateral multidirectional voluntary dislocations, multiple surgical attempts to achieve stability were ineffective. Joint laxity and hyperelastic tissue are underlying factors contributing to failure of stabilization. More importantly, voluntary dislocations often achieve secondary gain and need preoperative psychological evaluation. PMID- 2239191 TI - [The risk of thromboembolism in prosthetic surgery of the hip, and its prevention by administration of individualized heparin dosages]. AB - After hip replacement, thromboemboli remain a very frequent and severe complication. Different techniques of prevention have been described but there is no pharmacological method of definitively proving the effectiveness of such techniques. The use of low-dose heparin has been recommended, but owing to the variable results obtained in this type of surgery, certain authors prefer using an individualized dose. The authors report their experience with this regimen in 30 patients with certain individual thromboembolic risk factors who underwent hip arthroplasty. Despite these cases of deep vein thrombosis, no symptomatic pulmonary emboli were diagnosed. There were two patients with hematomas at the iliac crest which resolved without sequelae after drainage. The different rules to be followed for prevention of these complications are analyzed; the authors underscore the need for individual adaptation of the heparin dose. PMID- 2239193 TI - [Reflections on a small series of cementless total hip prostheses]. AB - We report on our series of 48 patients with uncemented hip prostheses, with an average follow-up of 3 years. The clinical results, according to the Merle d'Aubigne's classification, are comparable to those obtained with cemented prostheses except for transitory pain, very often localized to the lateral aspect of the thigh, which seems to be correlated with the bone adaptation to the implant. Radiological findings are valuable in the assessment of long-term results with uncemented prostheses. During the operation, it is of utmost importance that the surgeon obtain a very tight fit of the prosthesis into the bone, which must be confirmed on postoperative X-ray. Under such conditions, the radiological appearance remains the same, showing a condensation line outlining the cup and absence of radiolucent lines along the stem. On the other hand, cortical thickening, bony condensation around the tip of the stem and sclerotic lines are the radiological evidence of bone adaptation to the prosthesis. They are not indicative of a less good result. Finally, radiolucent lines wider than 1 millimeter, extending along the stem, or a progressive sinking of the femoral component are the radiological signs of implant instability. In these rare cases, the prognosis may be compromised. PMID- 2239194 TI - [Tibial fractures following Maquet's tuberosity advancement. Apropos of 2 clinical case reports]. AB - Although accustomed to using the Maquet tibial tuberosity advancement, the authors had two similar and rare complications in which a fracture of the tibial shaft occurred at the end of the vertical osteotomy. Both incidents arose from a mechanical incision effect. This can be prevented by making a larger circular hole in the distal portion of the osteotomy. PMID- 2239195 TI - Treatment of nonunion using pulsed electromagnetic fields: a retrospective follow up study. AB - Pulsed electromagnetic fields (PEMF) are a useful means of treating cases of fracture nonunion. In 67.7% of nonunions with a disability time of at least 24 months, complete consolidation was obtained. This success rate is increased to 76.6% if we exclude nonunion, that presented contraindications for treatment with PEMF. The disability time had no effect on the success rate. Lesions of the humerus and atrophic nonunion had an unfavorable prognosis. PMID- 2239196 TI - [Treatment of painful spondylolysis using Morscher's hook]. AB - An original technique of direct isthmic reconstruction described by E. Morscher was used in 25 patients with painful spondylolysis after failure of conservative treatment. After a follow-up of 25 months, the functional and radiological results were evaluated and compared with other techniques. Nineteen patients had an excellent or good functional result, in 2 patients the result was fair, and 4 patients had no beneficial effect on pain. The best results were seen in patients younger than 20 years, with an olisthy of less than 10 mm, without associated joint, disc or ligament pathology. In these cases, good results were achieved in 90%, and there was radiological consolidation in 100%. PMID- 2239197 TI - Surgical treatment of tibial pseudarthrosis using the Ilizarov apparatus. A critical analysis. AB - Since November 1985 the authors have added the Ilizarov procedure to their armamentarium for the treatment of tibial pseudarthrosis. The results of a first clinical study of 10 patients are reported. The mean duration of follow-up is 17 months. The consolidation rate is higher with a transverse than with an oblique pseudarthrosis. The Ilizarov procedure combined with a corticotomy offers new perspectives in the management of massive bone defects. In the presence of severe malalignment, a gradual reduction can be carried out. The main complications are pin tract infections and algodystrophy. PMID- 2239198 TI - The natural history of chondromalacia patellae. A 12-year follow-up. AB - A series of 45 patients with chondromalacia patellae demonstrated clinically and by arthrotomy, but without demonstrable biomechanical misalignment, was investigated retrospectively. Thirty-one of the patients had only been treated conservatively while partial chondrectomy was performed in 14. All of the patients underwent an intensive rehabilitation program. After 12 years the patients were interviewed. Eighty-one percent of the patients who were treated conservatively and 57 percent of the patients in whom partial chondrectomy was performed had mild or no pain and no other knee complaints. The results were better for patients aged 20 years or younger. Two patients received disability pensions on account of poor knee function and 6 had changed to less strenuous occupations. Restraint is advised as regards operative treatment of chondromalacia patellae. PMID- 2239199 TI - [Subcapital fracture of the femoral neck. A rare complication of a pertrochanteric fracture healed in coxa vara position]. AB - Subcapital stress fracture occurring after a previously healed intertrochanteric fracture is a rare event. One further case is reported. A new etiology and different ways of preventing such a complication are proposed. PMID- 2239200 TI - [Cauda equina syndrome due to early postoperative migration of an adipose tissue flap following laminectomy]. AB - The authors reported an early case of cauda equina syndrome after hemilaminectomy and discectomy for lumbar disc herniation. CT-scan revealed the migration of the free fat graft used for preventing peridural scar formation. Removal of the graft resulted in total patient's recovery. PMID- 2239201 TI - Subcapital fracture of the femoral neck following internal fixation with a dynamic hip screw. AB - A case of subcapital femoral neck fracture following osteosynthesis of a trochanteric fracture is described. The implant used was the dynamic hip screw. This kind of fracture is very rare, and has to our knowledge never been described with the use of the dynamic hip screw. PMID- 2239202 TI - 'Carrusel': an expert system for vestibular diagnosis. AB - Neuro-otology is the only field of otolaryngology in which diagnoses are mainly deductive. Although many technological advances have indeed occurred, the patient history still remains the most important part of the evaluation of a patient complaining of vertigo and/or dizziness. The use of artificial intelligence methods as an aid for the solution of clinical problems is not new. "Carrusel" is a Prolog build-up expert system dealing with the diagnosis of vestibular disorders that achieves a success rate of 97% when compared to the human experts involved in its design. PMID- 2239203 TI - Body sway stabilization in human posture. AB - Electromyographic (emg) responses and joint movements of the leg were analysed in subjects standing with eyes closed on a sinusoidally moving treadmill (0.16 Hz or 0.33 Hz, amplitude 33 cm). Activity in antagonistic leg muscles was reciprocally modulated, with a predominant gastrocnemius activation during deceleration of forward movement and tibialis anterior activation during deceleration of backward movement of the treadmill. In these phases, it was necessary to compensate for sway induced by body inertia. The match between treadmill movement and emg activity was better for the gastrocnemius than for the tibialis anterior muscle. The characteristic pattern of leg muscle emg activity is suggested to be modulated predominantly by vestibulo-spinal reflexes partly because treadmill movements did not evoke muscle strength, and partly because patients with loss of vestibular function showed basic alterations in the emg pattern and could only compensate for the slow sinus while standing unsupported. PMID- 2239204 TI - Head-shaking nystagmus during vestibular compensation in humans and rhesus monkeys. AB - Nystagmus evoked after rapid horizontal head-shaking is believed to be a sensitive indication of the existence and location of a unilateral vestibular lesion. Its origin is the directional asymmetry in vestibular responses of the healthy labyrinth (Ewald's second law). For nystagmus to appear after the head has stopped moving, however, the directionally asymmetric responses must have been stored during the head-shaking to be discharged afterwards. Our results confirm the notion that head-shaking nystagmus is most likely generated by a directional preponderance in vestibular responses but only in combination with a functioning central velocity-storage mechanism. If velocity-storage is lost completely, as may occur during the acute phase of a unilateral peripheral vestibular lesion, even a large vestibular preponderance does not lead to head shaking nystagmus. Thus, to interpret the results of the head-shaking test the condition of the velocity-storage mechanism must be taken into account. PMID- 2239205 TI - Significance of pressor input from the human feet in anterior-posterior postural control. The effect of hypothermia on vibration-induced body-sway. AB - The importance to postural control of the mechanoreceptors of the soles was investigated in thirteen healthy subjects. Body-sway velocity was evaluated before and after exposing the subject's feet to hypothermia, and when calf muscles were exposed to vibration at frequencies between 20 and 100 Hz. Subjects were tested both with eyes open and closed. Body-sway velocity was found to increase significantly during hypothermia of the feet. The difference in body sway between hypothermal and normothermal conditions was less prominent when the subject's eyes were open though the difference was significant in both cases. The present results indicate the importance of the mechanoreceptors of the soles to postural control and elucidate their interaction with compensatory visual input in maintaining postural control. These findings also suggest, that factors affecting pressor input should be taken into consideration when assessing patients with complaints of dysequilibrium. PMID- 2239206 TI - Galvanically induced asymmetric optokinetic after-nystagmus. AB - The effect of an asymmetric vestibular input on the symmetry of horizontal optokinetic after-nystagmus (OKAN) was studied in twenty healthy subjects. Optokinetic nystagmus (OKN) was elicited by a whole-field optokinetic drug, rotating at 90 degrees/s, and eye-movements were recorded by a DC electro oculographic technique (EOG). The ratio of OKAN following right and left-beating OKN respectively was computed. An asymmetric vestibular input was generated by a continuous bi-polar, bi-aural galvanic stimulus (1 mA) to the vestibular nerves during the optokinetic stimulation and the recording of the OKAN. During galvanic stimulation the relation between left and right-beating OKAN was asymmetric, compared with the OKAN found after optokinetic stimulation only. The galvanic stimulus caused a preponderance for OKAN with the fast phase beating toward the cathode. Thus, the small vestibular asymmetry induced by the galvanic stimulus, which was not strong enough to produce nystagmus by itself, caused an asymmetric OKAN. These findings suggest that examination of OKAN may be of value to detect small vestibular asymmetries in peripheral vestibular disorders in man. PMID- 2239208 TI - The influence of middle ear pressure on the vestibular nerve activity in cats. AB - The influence of middle ear pressure on the vestibular nerve activities was investigated in anesthetized cats. The vestibular nerve activities were recorded intraaxonally and positive or negative pressure was applied to the middle ear cavity through a tympanic membrane perforation. The firing of vestibular nerve fibers, especially the regular type nerve that responded to horizontal semicircular canal stimulation, increased with positive pressure and decreased with negative pressure. Most vestibular nerves that responded to anterior or posterior semicircular canal stimulation were not influenced by changes in the middle ear pressure. These results indicate that middle ear pressure load is transmitted to the vestibular end organs and then to vestibular nerve. PMID- 2239207 TI - Effects of anti-cholinergic and cholinergic drugs on habituation to motion in rats. AB - The effects of the anti-cholinergic drug scopolamine, an anti-motion sickness drug, and of the cholinergics physostigmine and neostigmine on habituation to motion sickness in rats were examined using pica, measured as eating of kaolin, as a behavioural index of motion sickness in rats. Rats were rotated around two axes for 1 h once a day for 10 or 11 days. Rotation-induced kaolin intake of control rats gradually decreased from day 9 of daily rotation. Test rats were not treated for the first 3 days, given drugs on days 4-7 of rotation and then again given no drugs for the next 3 or 4 days. Rotation-induced kaolin intake of test rats was compared to that of controls. Results showed that TTS (Transdermal Therapeutic System)-scopolamine administration facilitated habituation to rotation, whereas physostigmine, a centrally acting cholinesterase inhibitor, suppressed it, and neostigmine, a peripherally active cholinesterase inhibitor, had no effect on habituation at all. These findings suggest that the central cholinergic neuron system plays an important role in the neural mechanism of habituation to motion in rats. PMID- 2239209 TI - Effect of perilymphatic air perfusion on cochlear potentials. AB - Perilymphatic fistula is now widely recognized to cause acute profound hearing loss. It is still controversial, however, which mechanism it is that causes the reversible hearing loss. Recently, it has been suggested by two groups of researchers that the intrusion of air bubbles into the perilymphatic space (a condition called pneumolabyrinth or aerolabyrinth) through the ruptured labyrinthine window(s) may be one of the causes. In order to examine the mechanism underlying the hearing loss associated with pneumolabyrinth, the perilymphatic space of the guinea pig cochlea was perfused with air and cochlear potentials were recorded. Although perfusion of the scala tympani with air at a rate as high as 200 microliter/min caused an immediate and drastic decrease of the cochlear microphonics (CM) and the compound action potential (AP), it had little effect on the endocochlear dc potential (EP) during perfusion for 20 min. A decline in EP was seen in half the ears, but only when the duration of perfusion exceeded 30 min. These results show that the EP has an amazing resistance to air trapped in the scala tympani of the cochlea and that the initial decrease of hearing acuity after the elimination of perilymph from the scala tympani (or introduction of air into the scala tympani) is probably due to interference in CM and AP generation mechanisms rather than to strial dysfunction. PMID- 2239210 TI - Quantum type bone remodeling in the otic capsule of the pig. AB - Normal quantum type bone remodeling was studied in temporal bones of young domestic pigs by means of combined microradiography, osteofluorochrome labelling and osteoid staining. Evolving secondary osteons were morphologically normal although much less in the otic capsule than in the surrounding compacta of the temporal bones or in long bones. Moreover, remodeling was totally absent in bone tissue immediately adjacent to perilymphatic spaces suggesting the presence of a local mechanism controlling resorption and perhaps formation in the bony otic capsule. PMID- 2239211 TI - Distribution of glycoconjugates during cochlea development. A histochemical study. AB - Specific occurrence and distribution of glycoconjugates in the developing mouse cochlea was investigated using Alcian blue/PAS staining. The AB/PAS positive staining occurred intracellularly, extracellularly, pericellularly, and as glycocalyx. Pericellular staining occurred between certain epithelial cells in early stages of development, and extracellular deposit occurred mostly in mesenchymal tissue surrounding the cochlear duct and later in developing spiral ligament. During early stages of development, mesenchymal tissue and pericellular space of different epithelial cells of the cochlear duct were intensely stained, suggesting that these glycoconjugates may play an important role in the differentiation of the cochlear structures. Different supporting cells (e.g. Deiters' cells, pillar cells) were intensely stained at different development stages coinciding with the time when the subcomponents of the tectorial membrane (TM) were being formed. This finding suggests that glycoconjugates in the TM are produced by these cells. PMID- 2239212 TI - Ultrastructure of ampullar dark cells in the absence of circulating adrenocorticosteroid hormones. AB - The morphology of rat ampullar dark cells was studied in the absence of circulating adrenal hormones at two time intervals of 8-14 and 22-28 days. Five morphological parameters of dark cells were quantitatively determined: cell area per baseline length, basolateral membrane surface density, basolateral membrane length per baseline length, volume density of intercellular space and volume density of vacuoles. Significant statistical reduction of basolateral membrane length per baseline length was observed after an absence of circulating adrenal hormones for 8-14 days and 22-28 days compared to sham operated animals that served as control. The basolateral membrane surface density decreased significantly in the animals sacrificed 22-28 days following adrenalectomy compared to sham operated animals. Cell area per baseline length decreased and volume density of vacuoles increased at both time intervals following adrenalectomy; however, these differences were statistically insignificant. The volume density of intercellular space between dark cells was practically constant among the groups. Results of this study are similar to those reported for ion regulating nephron cells, and support the hypothesis that cells involved in microhomeostasis of vestibular endolymph may at least be partly regulated by adrenal hormones. PMID- 2239213 TI - Mitochondrial volume density of Schwann cells associated with rat vestibular ganglion cells. AB - The purpose of this study was to quantitate the mitochondrial volume density (MVD) within Schwann cells associated with vestibular ganglion cells in the female Wistar rat. Results show that this type of Schwann cell (SC) has a significantly higher MVD (19.4% +/- 1.9) than that reported for myelinating SC of peripheral nerve (1-5%). This large difference in SC MVD may be related to the energy requirements needed to maintain the local ion homeostasis around the ganglion cells given the environmental differences created by the different barrier systems of these regions of the nervous system. PMID- 2239214 TI - Involvement of cochlear nerve in acoustic tumours. AB - With conventional light and transmission electronmicroscopy we studied 10 cases of acoustic nerve tumour, 3 of which proved to be instances of von Recklinghausen neurofibroma and 7 of schwannoma. Schwannomas were not found to infiltrate the cochlear nerve. Hearing loss, if present in cases of schwannoma, could be related to non-specific lesions of the uninfiltrated cochlear nerve in the vicinity of the vestibular nerve tumour. Only neurofibromas were found to infiltrate the cochlear nerve. Distinction between tumour infiltration and non-specific lesion could be made by electron microscopy. PMID- 2239215 TI - Three-dimensional graphic reconstruction of the tympanic bulla of the rat with special reference to the middle ear muscles. AB - On the basis of functional questions, graphic three-dimensional reconstructions of the tympanic bulla of the rat were made to gain insight into the spatial organisation of the contents of the bulla and especially of the tympanic membrane -ossicular chain--middle ear muscle complex. For this purpose drawings of microscopical sections of complete bullae were fed into the computer to make three-dimensional graphic reconstructions with hidden line removal. From these reconstructions plastic representations were made by the medical artist. The topographical anatomy of the tympanic bulla is discussed in detail and compared to the anatomy of the middle ear in man. It is postulated that, despite differences in spatial organisation of the middle ear of the rat compared to that of man, the middle ear muscles influence the ossicular chain in a comparable way. On the basis of the topographical anatomy it is feasible that the muscles in the rat act synergistically in increasing the stiffness of the ossicular chain. PMID- 2239216 TI - Anatomic variations of the chorda tympani canal. AB - The anatomic variations of the facial recess are of interest in certain otosurgical procedures. The medial border of the recess is the mastoid portion of the facial nerve canal, and the lateral border is the bony canal of the chorda tympani. These two structures were investigated in 64 polyester casts of temporal bone specimens. The point of exit of the chorda tympani canal from the facial canal was assessed together with the angle, formed between these two nerve channels. As a further way of describing the spaciousness at the facial recess, the distance between the sulcus of the stapedius muscle and the chorda tympani canal was evaluated. PMID- 2239217 TI - Changes of middle ear mucosa in secretory otitis media treated with ventilation tubes. AB - The present study was designed to obtain the precise ultrastructural status of the middle ear mucosa of patients to whom ventilation tubes were applied for the treatment of secretory otitis media (SOM). This study comprised 14 children with SOM aged 5-11. Normal epithelium obtained from otosclerotic patients as controls was composed of three main cell types; basal, ciliated, and secretory. Electron microscopic observations revealed that ciliated cells were almost completely absent in the epithelium of patients with SOM. Secretory cells, on the other hand, were noted to be increased in number with cytoplasmic features indicating active secretory phase; abundant secretory granules in these cells featured both serous and mucoid characteristics. Following the application of ventilation tubes, the micrographs exhibited a vast number of ciliated cells. Furthermore, the secretory cells were less conspicuous and the secretory granules were mostly serous in type. The ultrastructural findings of this investigation strongly suggest that the application of ventilation tubes in cases of SOM stimulates ciliated cell regeneration, inhibits secretion of mucoid material, and activates serous secretion; all of which eventually shorten the recovery period. PMID- 2239218 TI - Amoxicillin/clavulanate treatment in secretory otitis media. Bacteriological findings in the nasopharynx. AB - A double blind, placebo controlled study was undertaken to evaluate the antibiotic impact of amoxicillin/clavulanate acid on the nasopharyngeal flora in children treated for 4 weeks for secretory otitis media (SOM). In 131 children who received antibiotic, a significant fall in H. influenzae and S. pneumoniae was observed in comparison to 133 children who received placebo. Beta-haemolytic streptococci and S. aureus were less frequent and did not decrease significantly. One month after discontinuation of treatment the nasopharyngeal bacterial flora was restored to pretreatment level. Seasonal variation was found only for S. pneumoniae. No persistent beta-lactamase producing H. influenzae was noticed. In the light of previously published results this study confirms that the nasopharyngeal flora plays an aetiological role in the development of SOM in children, and that the used antibiotic did not disturb the nasopharyngeal flora in the long run. PMID- 2239219 TI - Effects of middle ear ventilation on cholesteatoma development in experimental animals. AB - This study was designed to evaluate the effect of middle ear ventilation on cholesteatoma formation following propylene glycol application in experimental animals. Fifteen chinchillas had stainless steel ventilation tubes chronically implanted in their bullae and 60% propylene glycol was subsequently instilled into the middle ear cavities. The animals were kept alive for 4 weeks, during which time the middle ear pressure was monitored tympanometrically and the tubes were frequently inspected to verify patency. Of the 30 ears in the study, 20 (66.6%) developed middle ear cholesteatoma--a rate of occurrence comparable to that found in earlier studies in which middle ear ventilation was not provided. These results indicate that negative middle ear pressure is not a necessary factor for cholesteatoma development following application of chemical irritants in experimental animals. PMID- 2239220 TI - Nasal physiology in swimmers and swimmers' sinusitis. AB - To investigate the pathogenesis of swimmers' sinusitis we questioned and examined a group of 20 swimmers and 20 controls. Clinical examination was followed by rhinomanometry, sonography of the maxillary sinuses, a saccharine test to assess mucociliary transport in the nose, and a viable cytological sampling of the nasal mucosa. The history showed a preponderance of symptoms of sinusitis and chronic rhinitis in the swimmers' group, as well as a reddening of the nasal mucosa and a swelling of the adenoids. Sonography showed mucosal thickening in the antrum in more cases among the swimmers. Rhinomanometry, saccharine test, and viable cytological sampling revealed no differences of significance between the groups. It is discussed that pathogenesis is more probable through cooling of the skin of the face and the whole body than by entrance of water into the upper respiratory tract. PMID- 2239221 TI - Age-dependent changes in bacterial adherence to epithelial cells of nasopharynx in vivo. AB - Epithelial cells were scraped from the posterior wall of the nasopharynx (NPH) of 20 consecutive patients (age range 1 to 52 years, 9 males, 11 females) undergoing ENT surgery under general anaesthesia. The cellular mixture was immediately homogenized, filtrated through a 5 microns pore filters and centrifuged (10 min, 1,500 rpm). Non-ciliated, squamous epithelial cells caught by the filter were harvested and stained with acridine orange. Epithelial cells with bacteria attached were evaluated when specimens were examined under a fluorescence microscope. A distinct difference was noted between young individuals and adult patients regarding bacterial adherence to nasopharyngeal epithelial cells, adherence in young patients being especially remarkable. Bacteria appeared not to attach to ciliated epithelial cells. The high incidence of otitis media infections among young individuals may be due to the remarkable bacterial adherence to nasopharyngeal non-ciliated epithelial cells in this age group. PMID- 2239222 TI - Mucosal blood volume and oxygen saturation in the human vocal fold. AB - With a newly developed spectrophotometric analyzer we were able to measure hemoglobin (Hb) concentration and its oxygen saturation in the human vocal and ventricular folds. Studies were made on 30 subjects including 18 normal controls. In laryngomicrosurgery under general anesthesia, measurements were made with a fiber probe touching the laryngeal mucosa. Results were as follows: In normal mucosa of the vocal fold, the mean value of IHb was 40 and the ISO2 was 55, while in that of the ventricular fold, the mean values were 74 and 56, respectively. Thus, in spite of the influence of general anesthesia, the mucosal blood volume was lower in the vocal fold than in the ventricular fold. The mean value of IHb was 30 in the vocal fold polyps, 122 in the vocal fold nodule, 43 in the polypoid degenerations, 17 in the vocal fold cyst, 62 in the granuloma, 6 in the sulcus vocalis and 19 in the hyperkeratoses. This method is considered useful for objective and quantitative analysis of pathological conditions in the vocal fold. PMID- 2239223 TI - Expression of epidermal growth factor receptor in laryngeal dysplasia and carcinoma. AB - The immunoreactivity of epidermal growth factor receptor (EGFR) was studied in laryngeal biopsy specimens from 24 patients. The study comprised 5 cases of normal laryngeal mucosa, 5 cases of dysplasia, 7 cases of well differentiated squamous cell carcinoma, and 7 cases of poorly to moderately differentiated squamous cell carcinoma. EGFR was in general not expressed in normal and dysplastic epithelia, whilst all carcinomas showed a rather strong positive immunoreactivity. There was no significant difference in staining patterns between the well and poorly to moderately differentiated carcinomas. The results suggest that EGFR constitutes a component of neoplastic, but probably not preneoplastic, laryngeal disease. The study failed to reveal any difference in staining pattern between different types of laryngeal squamous cell carcinoma. PMID- 2239224 TI - Scanning electron microscopy in a case of infantile inborn deafness. AB - The temporal bones of a one-year-old, congenitally deaf boy were removed 3 1/2 days post mortem, fixed in formaldehyde and prepared for scanning electron microscopy (SEM). In the apical coil the organ of Corti had the normal configuration. In the second coil there was a continuous decrease of both the number of sensory cells and their conservation. Altered sensory cells with giant or bullous distended hairs were found. Throughout the basal coil the hairs of the sensory cells were absent, while the other cells of the organ of Corti appeared normal. PMID- 2239225 TI - Histopathological changes in the temporal bone in Bell's palsy. AB - The changes in the facial nerve at autopsy are described in a case in which there had been an acute onset of lower motor neurone facial paralysis, with a clinical diagnosis of Bell's palsy, 11 days before death. There was congestion and infiltration of the nerve in the internal auditory meatus and proximal fallopian canal by lymphocytes. Features indicating compression of the nerve in the proximal part of the fallopian canal were seen in the presence of congestion and osteoclastic resorption of the bone surrounding the proximal fallopian canal. Demyelination was present in the tympanic part of the nerve. A bulge below Bill's bar was found on the normal as well as the pathological side and cannot be accepted as evidence of pathological change. It is suggested on the basis of the pathological findings that the symptoms of Bell's palsy may arise from compression of the facial nerve in the proximal part of the fallopian canal. PMID- 2239226 TI - Immunohistochemistry of otosclerosis. AB - Immunoglobulins G (IgG) and A (IgA) were found in plasma cells, osteocytes, chondrocytes and in connective tissue of active otosclerotic (= otospongiotic) lesions. The application of antibodies against paramyxovirus and rubella virus antigens reproducibly determined the expression of these antigens at different sites in the otosclerotic stapes, but also in the epithelial cells of the overlying middle ear mucosa. By using specific T-lymphocyte and B-lymphocyte markers, about 80% of the lymphocytes present in the otosclerotic footplate were revealed to be T-lymphocytes. There was neither deposition of immunoglobulins nor any expression of viral antigens in non-otosclerotic footplates which were investigated as controls. PMID- 2239227 TI - Methods for cellular and subcellular visualization of intermediate filament proteins in the human inner ear. AB - The preservation of antigenicity for monoclonal antibodies (mAbs) directed against the five classes of intermediate filament proteins and their subgroups was analysed in inner ear specimens from both early embryonic (6-8 gestation-week old) human labyrinths and inner ears from newborn CBA/CBA mice. After initial fixation in 2% paraformaldehyde, the specimens were embedded in either polyvinyl alcohol (PVA) or the low viscosity acrylic resin LR White. Both embedding media allowed sectioning at room temperature with a specimen thickness of 0.5-1 microns, which gives a resolution at the subcellular level in the light microscope. Immunoreactivity occurred in the PVA-embedded material, but not in specimens embedded in LR White. However, considerably fewer mAbs showed immunostaining in the PVA-embedded material than in both cryofixed-cryosectioned or paraformaldehyde-fixed-cryosectioned human inner ears. Immunoelectron microscopy using colloidal gold (particles 10 nm in diameter) was successful in the PVA-embedded (but not the LR White-embedded) material. PMID- 2239228 TI - Investigation of intracellular organelles in the human organ of Corti using backscattered electrons (BSE). AB - Using ligand-mediated osmification (OTOTO technique), human cochleae were prepared for scanning electron microscopy. The surface of the organ of Corti and the bodies of the sensory cells were observed with secondary and backscattered electrons. Detecting the backscattered electrons emitted from the depth of the cells, intracellular organelles such as subsurface cisternae, mitochondria and nuclei became visible in their reciprocal arrangement. PMID- 2239229 TI - Clinical experience with early post-mortem human inner ear perfusion. AB - Early fixation of human temporal bones is a difficult but very important task. The author reports on his experience in hospital wards. PMID- 2239230 TI - Preservation of the human cochlea with two different fixatives. AB - The cochlear morphology of eight inner ears from 4 patients was studied by electron microscopy. The perilymphatic perfusion was performed in 2 of them 2 and 2 1/2 h and in 2 others, 10 and 11 h post mortem. In each patient, Karnovsky's fixative was used in one ear and Britta's fixative in the other. No structural differences between the two ears were ascertained in the patients with a short post-mortem fixation time. The cochleas with 2 h post-mortem fixation time were better preserved than those with the 10 and 11 h delay. The cochleas with the longer delay from death to perilymphatic perfusion were still fairly well preserved. However, in these cochleas the stronger fixative (Britta's fixative) gave a better preservation. PMID- 2239231 TI - Progress in temporal bone histopathology. III. An improved technique for immunohistochemical investigation of the adult human inner ear. AB - A new tissue processing technique is described for immunohistochemistry of the adult human inner ear, avoiding the immuno-compromising step of prolonged decalcification. The procedure allows reliable investigation of frozen sections of the chemically fixed, non-decalcified, adult human cochlea and vestibular sense organs. Preservation of immunoreactivity, combined with satisfying tissue morphology, is illustrated by the immunohistochemical localization of the intermediate filament constituents cytokeratins and neurofilament proteins throughout the membranous labyrinth. PMID- 2239232 TI - Human auditory and vestibular pathology--studies of early development, ageing and disease. Proceedings of the Fifth Workshop on Histopathology of the Human Audio Vestibular Organ. Milan, 25-27 June 1989. PMID- 2239233 TI - Developmental aspects of the human endolymphatic sac. PMID- 2239234 TI - Early bone formation in the human fetal otic capsule. A methodological approach. AB - The present study was concentrated on the use of energy-dispersive X-ray analysis and backscattered electron imaging as practical tools for advanced autopsy of human fetuses when diagnostic evaluation of ear pathology is required. These methods were used to revisit the primary calcification front of the fetal otic capsule between 18 and 36 weeks' gestational age. Energy-dispersive X-ray analysis indicates an equal Ca/P ratio in all the three layers of the otic capsule. These results are discussed in view of calcium homeostasis and inner ear function. PMID- 2239235 TI - Quantitative evaluation of the human cochlear nerve. AB - In 18 human temporal bones of patients with normal hearing or sensory neural deafness, the cochlear neurons were evaluated at the level of the peripheral axons in the osseous spiral lamina, the ganglion cells in the spiral ganglion and the central axons in the cochlear nerve in the inner acoustic meatus. The total number and the segmental distribution were both determined. PMID- 2239236 TI - Transmission electron microscopy of previously embedded celloidin sections. AB - A technique to re-embed celloidin sections of human temporal bones for transmission electron microscopy (TEM) is presented. The procedure consists of basically four different steps, starting with loosening of the celloidin sections from the glass slides, removing the celloidin using clove oil, to staining and embedding in epoxy resin. The technique allows TEM analysis of the intact labyrinth in various regions in the same specimen, as well as on the same section. This may prove useful, as prior dissection of the fragile tissue components of the membranous labyrinth is not longer necessary. The technique makes possible the retrospective study of temporal bone collections. It may also be of value for the study of the ultrastructural histopathology of the human inner ear in optimally preserved tissue. PMID- 2239237 TI - Quantitative analysis of cochlear sensory cells and neuronal elements in man. AB - The myelinated radial fibres in the osseous spiral lamina and the myelinated fibres in the cochlear nerve in the internal auditory canal as well as the sensory cells were counted in cochleae from 15 dissected temporal bones from 8 patients. Light microscopy was carried out on semithin sections of epoxy resin embedded tissue. Audiometry had been performed within 6 months prior to death. Three patients had normal hearing for their age group, 2 had slight presbyacusis and the remaining 3 had sustained noise injury. All specimens clearly had fewer fibres in the spiral lamina than in the internal auditory canal. The cochleae from patients with normal hearing for their age group had a difference in the nerve fibre counts of up to 34%. A case of sensorineural presbyacusis showed 31%, and a case of neural presbyacusis, 47% difference. The greatest difference was found in a case of acoustic trauma, the range in this group being between 25% and 55%. The lower the number of fibres in the spiral lamina, the greater was the difference in all but two specimens. A slow retrograde degeneration, i.e. beginning in the peripheral process of the cochlear nerve, could be an explanation for these findings. PMID- 2239238 TI - Ultrastructural aspects of the human peripheral vestibular system. AB - The sensory epithelia from the membranous labyrinths of 4 patients were examined by transmission electron microscopy. The distribution ratio of type 1 to type 2 cells was recorded, compared for each sensory area and correlated with age. An ultrastructural assessment confirmed generalized patterns consistent with autolytic and preparation artefact, viz. calyceal dilatation, cytoplasmic protrusions and some sensory hair loss. More specific features, i.e. lipofuscin accumulation, membrane-bound inclusions and neural degeneration were consistent with pre-mortem pathological change. In 2 patients, total nerve fibre counts of 15,766 and 19,741 were obtained. Total fibre counts correlated with the sensory cell density of the innervated areas. Differential counts of the superior and inferior vestibular nerves suggested that there was a reduced number of fibres in the superior division of both patients, in comparison with established normative data. Morphometric analysis of the constituent fibre diameters revealed a skewed distribution with a modal value of 6 microns for both patients. PMID- 2239240 TI - Acoustic trauma in mineworkers revealed by temporal bone necropsy. AB - Six selected human cochleae showing definite signs of mechanical damage caused by exposure to high intensity noise (acute acoustic trauma) are reviewed. Patterns of degeneration of cochlear hair cells were compared with the functional audiometric examinations. Tonotopic relations, mechanism of damage to the organ of Corti as well as pathological changes of the tectorial membrane are discussed. PMID- 2239239 TI - Observations on the pattern of sensorineural degeneration in the human cochlea. AB - Cochlear sensory and neural degeneration was examined in nine pairs of human temporal bones fixed by perilymphatic perfusion, using phase-contrast and electron microscopy. Four pairs, three from females, had only slight sensorineural degeneration, limited to the very basal end of the cochlea. A predominantly neural degeneration was identified in a 54-year-old male. The process was bilateral, asymmetrical, uneven, and involved the entire length of the cochlea with several circumscribed areas of severe nerve degeneration. One case had mild, diffuse sensorineural degeneration in the lower half of the basal turn characteristic of presbyacusis. The other three pairs, all from males, revealed sensorineural degeneration patterns associated with noise injury and were remarkably similar to or almost identical with cochleas described previously. There was a good correlation between the presence of supporting cells and the survival of nerve fibres in the osseous spiral lamina in the corresponding area. In one cochlea, however, the degeneration of only inner hair cells in a small area was associated with complete nerve degeneration in the corresponding sector of the spiral lamina. Giant cilia were frequently seen in the apical turn. PMID- 2239241 TI - Aeration of the tympanomastoid cavity and the Eustachian tube. AB - Physiological changes in body position affect the degree of opening and closing of human auditory tubes. Notable changes were observed in lateral body position concerning the opening rate of the auditory tubes, which corresponds to the changes in pressure within the lower portion of the middle ear cavity. This physiological mechanism seems to be related with the anatomical direction of the auditory tube and the natural mechanism for the protection of the middle ear cavity. When a change takes place which moves the compliance of the eardrum to the positive side (e.g. head position change or static lateral body position), observation suggests the possibility of venostatis and production of gas. Measurement of the oxygen tension in the middle ear cavity under atmospheric pressure revealed the existence of constant gas production which maintains the pressure in the middle ear cavity at the same level as atmospheric pressure. This result denies the influx of gas from the atmospheric environment into the middle ear cavity. These results stem from the intrinsic physiologic mechanism of the middle ear cavity, namely maintenance of effective auditory sound conduction (a function to keep eardrum compliance as close to zero as possible), by keeping the pressure within the middle ear cavity below the atmospheric pressure, either at the same level as or slightly higher than that of the environment pressure. Gas emission from the middle ear cavity in the atmospheric environment and a low oxygen tension are a natural physiologic mechanism to protect the middle ear cavity from infection and other hazards. PMID- 2239242 TI - New findings in observations by tubo-tympano-aerodynamic method. AB - We studied Eustachian tube function of healthy adults by two air flow methods, namely tubo-tympano-aerodynamic graphy by Valsalva maneuvre, and Tyonbee maneuvre during swallowing. We observed for the first time the presence of reciprocal features in normal Eustachian tubes. We also compared the tubal function of the same group using an air flow method and sound transmission method. The results of these observations showed that 77.4% of the subjects were positive for TTAG in Valsalva pattern, and 85.4% for sonometry. It can be inferred that data on the tubal opening in response to Valsalva and Toynbee maneuvres is obtained more easily by sonometry than by TTAG. TTAG, which permits examination of minute changes in air flow dynamics even in healthy Eustachian tubes, provides more important information on tubal function than does sonotubometry. PMID- 2239243 TI - Middle ear ventilation mechanism. AB - The ventilation mechanism of the middle ear is very important as regards the pathogenesis of middle ear disease, but its mode of function is still obscure. Therefore, we tried to measure the ventilation and clearance of the middle ear using radio-isotope imaging techniques and 133Xe in order to gain a clearer picture of the ventilation mechanism. In normal Eustachian tube cases, approximately 10% of the initially insufflated gas immediately entered into the middle ear cavity and mastoid air cells. The gas introduced into the middle ear diminished at a rate of 8% of volume per hour in the normal resting state. Two hours after the first procedure, air was insufflated, and gas volume in the middle ear cavity immediately diminished by 30%. In stenotic tube cases, it proved difficult to insufflate the gas into the middle ear, however, its diminishing rate with the passage of time was slightly faster than in normal tube cases. From this data, it was evident that air could easily and quickly enter into even the periphery of the mastoid air cells by insufflation via the Eustachian tube, despite the fact that the middle ear and mastoid air cells form a closed cavity. In the resting state, moreover, the air in the middle ear was thought to be absorbed mainly into the middle ear mucosa at a regular rate. It was confirmed that the insufflation procedure as a therapy for tubal stenosis and OME is very useful for the ventilation of the middle ear. PMID- 2239244 TI - PO2 levels in middle ear effusions and middle ear mucosa. AB - We measured PO2 values in mucoid and serous middle ear effusions (M-MEE, S-MEE) and in the middle ear mucosa of patients with otitis media with effusion (OME) and compared these values with those obtained from patients with middle ear barotrauma (MEBT). The mean and S.D. values of PO2 in M-MEE, S-MEE and MEBT effusions were 28.9 +/- 11.3, 31.5 +/- 9.5 and 37.0 +/- 15.4 mmHg, respectively; the mean and S.D. values in mucosa were 27.1 +/- 11.9, 27.0 +/- 13.2 and 32.5 +/- 1.0 mmHg, respectively. In health, PO2 values in middle ear mucosa are regulated by its blood supply, oxygen solubility in blood and the blood-to-cavity partial pressure gradient of the gas. When the Eustachian tube (ET) function is severely impaired, PO2 values in the middle ear air cavity depend on the mucosal condition, though some studies have shown a lack of relationship between ET function and PO2 values. Our results show that PO2 values in MEBT are consistently higher than in OME, suggesting that the attributable factor could be a better ET function in MEBT. PMID- 2239245 TI - Eustachian tube and middle ear diseases. PMID- 2239246 TI - Evaluation of clearance function of the Eustachian tube by sequential contrast CT. AB - Comparisons of Eustachian tube (ET) functions studied by sequential contrast computerized tomography (CT) and by tubotympanic aerodynamics (TTAG) were made. ET clearance function was assessed by the shape of the cartilaginous portion before, during and at the end of swallowing; ventilatory function was studied by TTAG. ET clarity, real-time dynamics and resolution were all better when observed with sequential CT. Contrast medium was instilled into the middle ear via a drumhead perforation and 1 scan/sec taken during swallowing. We classified ET function based on the presence or absence of a) movement of the cartilaginous portion, and b) contrast medium in the ET as i) movement present, contrast medium seen in ET: ii) movement absent, contrast medium present in ET; and iii) movement present, no contrast medium in the ET. Ventilatory and clearance functions did not parallel one another, attributable to some mechanical, differences between the two functions. PMID- 2239247 TI - Eustachian tube function in OME patients with cleft palate. Special reference to the prognosis of otitis media with effusion. AB - Eustachian tube function was investigated in two groups of cleft palate patients who had otitis media with effusion. One group consisted of 16 ears that healed after one ventilatory tube insertion, the other consisted of 33 ears that needed repeated tube insertion and did not heal in 2 years. The latter group was characterized by low opening pressure and inability to sustain lower middle ear positive pressure. This decrease force in the Eustachian tube was considered to be related to the prognosis of otitis media with effusion in patients with cleft palate. PMID- 2239248 TI - Eustachian tube function and mastoid pneumatization. AB - We investigated the relationship between the Eustachian tube's ventilatory function and the pneumatization of mastoid air cells. In 65 adults (66 ears) with chronic otitis media (COM), ventilatory Eustachian tubal function was evaluated by the inflation-deflation test, while the area of mastoid air cells was measured by the rectangular method on X-ray film. Group I represents good function in both the inflation and deflation tests. Group II represents good function in the inflation test but poor function in the deflation test. Group III represents a poorly functioning Eustachian tube in both tests. The opening pressure in Group III was statistically higher than in Group I and Group II. The area of mastoid air cells in Group I was statistically larger than in Group III. There was no correlation between opening pressure and area of mastoid air cells in COM. Postoperative failure of the tympanic membrane was frequently found in Group III. We discuss the tubal function and pneumatization of mastoid air cells. PMID- 2239249 TI - Prognosis of otitis media with effusion in children, and size of the mastoid air cell system. AB - We studied 334 ears in 176 patients who were chosen from children diagnosed as having otitis media with effusion (OME) at our clinic. These 176 patients were re examined about 5 years and 10 months after the first visit and categorized into three groups according to otological findings at the time of review: group A (normal), group B (sequelae), group C (OME). For this study, 168 ears of 86 persons were examined by roentgenography both at the time of the first visit and at review, and the size of mastoid pneumatization and differences in size between the three groups were compared. The results of the investigation can be summarized as follows. The size of mastoid pneumatization in group A was large at the time of the first visit and the increase in size was also greater than in the other two groups. These results led us to conclude that the degree of mastoid pneumatization is an important prognostic sign of the clinical course of OME and provides important information about treatment. PMID- 2239250 TI - Suppressed mastoid pneumatization in cholesteatoma. AB - Mastoid pneumatization size was studied by X-ray in 289 patients with otitis media (134 with cholesteatoma and 155 with chronic suppurative otitis media (COM) and 73 patients with traumatic tympanic membrane perforation (controls). The results demonstrated that mastoid pneumatization in the diseased ear of cholesteatoma patients was greatly suppressed. In these patients, the contralateral ear also showed significant suppression compared with controls; mastoid pneumatization size in the healthy ear contralateral to cholesteatoma was similar to that in patients cured of otitis media with effusion (OME). Hence, we conclude that cholesteatoma is a sequela of OME in childhood. PMID- 2239251 TI - Effects of myringotomy and orally administered drugs on viscosity and elasticity of middle ear effusions from children with otitis media with effusion. AB - Clinical and rheological studies were performed on 42 children with otitis media with effusion. Twenty-one patients received S-carboxymethylcysteine (group A), and the other 21 patients were administered Kampo medicine (group B), a Japanese traditional herbal medicine, for 4 weeks following myringotomy. At the end of the 4-week treatment period, 47.2% of the ears in group A and 40.5% in group B were regarded as being free from middle ear effusion (MEE). For rheologically thick MEEs, where the viscosity (eta') and elasticity (G') are much greater than the optimal values for mucociliary transport, post-treatment values of eta' for group A decreased significantly, but those of G' did not, in comparison with pre treatment values. No such changes in either eta' or G' were observed in group B. Results suggests that the combined therapy for myringotomy and oral SCMC is effective for improving the rheological properties of thick MEE in children. PMID- 2239252 TI - Is change in middle ear air volume following ventilation tube insertion a reliable prognostic indicator? AB - Ninety ears (52 patients, aged 3-11 years) affected by secretory otitis media (SOM) were treated by insertion of a ventilation tube (VT). Following VT insertion, the middle ear air volume of these ears was estimated by using an impedance audiometer, at 1, 3, and 6 months postoperatively, and every 6 months thereafter. The middle ear air volume, expressed as the compliance value, increased rapidly for the first 3 months, followed by a gradual increase thereafter. A great difference was observed among the compliance values of ears, ranging from over 10 cc to below 1.5 cc at 6 months, postoperatively. Twelve percent of the ears had compliance values of less than 1.5 cc, and in this group, CT showed opacified and poorly developed mastoid cells. Although the association of upper respiratory disorders such as chronic sinusitis, nasal allergies and cleft palate were found to be more frequent in cases of ears with smaller compliance values, this was not statistically significant. Small compliance values (middle ear air volume) were correlated with the early onset of acute or secretory otitis media, repeated otorrhea after VT insertion and high recurrence rates after the extrusion of the VT. PMID- 2239253 TI - Eustachian tube function in tympanoplasty. AB - Prognostic value of preoperative Eustachian tube function was examined in 77 ears subjected to type 1 tympanoplasty. Eustachian tube function was evaluated by positive and negative pressure equalization tests, and clearance test. Based on the results of these three tests, the ears were classified into four grades. The outcome of the ear surgery was judged by postoperative hearing, presence of otorrhea, atelectasis and perforation of the eardrum. Results of the positive pressure equalization and clearance tests of the tube were correlated with the outcome of ear surgery, although the negative pressure equalization test had no correlation with it. The percentage of unsuccessful outcomes increased with the grade of tubal dysfunction, indicating that tubal function is closely associated with the outcome of ear surgery. Thus, it was revealed that the preoperative tubal function test including positive pressure test and clearance test are useful for predicting the prognosis of ear surgery. PMID- 2239254 TI - The vascular anatomy of the vestibular labyrinth in man. AB - 1. A survey of the literature on the vascular anatomy of the vestibular labyrinth in Man is presented, and the methods of investigation used to visualize the vessels are evaluated. A generally correct picture of the subject is provided by the various studies published since Siebenmann's monograph. There are, however, some conflicting points as well as some lack of data with regard to the course and relationships of the large vessels and the capillary areas of the cristae and maculae. 2. This study presents a systematic description of the vascular anatomy of the vestibular labyrinth in Man, from the main arterial and venous stems to the capillary areas, with particular attention to the relationships between the vessels and the osseous walls, neural, and membranous structures. The vessels were visualized by a composite method including the selective injection of the internal auditory artery with coloured silicone or India ink; the counterstaining of the labyrinth with osmic acid; the cutting of the petrous bone in 1-mm thick, serial sections that were cleared with methylsalicylate. The sections were studied by stereomicroscopy, using mainly reflected light. Photos and drawings were made to illustrate the findings. New names were introduced for vessels hitherto unnamed, and some traditional names were modified in order to give a more precise and descriptive terminology. 3. The description followed the two main arteries, the capillary areas and the three main veins. The vestibular labyrinth is supplied by the superior vestibular artery and by the inferior vestibular artery which is a branch of the vestibulo-cochlear artery. The superior vestibular artery runs along the anterior aspect of the vestibule from the utricular nerve up to the cristae of the superior and lateral canals. It supplies the macula of the utricle, the cristae and ampullar crures of the superior and lateral canals. The inferior vestibular artery runs mainly along the medial wall of the vestibule. It supplies the last tract of the scala media and the vestibular caecum with a peculiar pattern which appears to be an adaptation of the common cochlear arrangement to the different spatial condition. It also supplies the macula of the saccule, the crista and ampullar crus of the posterior canal as well as the simple crures of the three canals. The vascular arrangement of the maculae and cristae has a similar three-layered architecture.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2239255 TI - [The effect of a histamine nasal provocation tests on the results of the tubal compliance manometry test (TCM) in normal study subjects]. AB - The Tubal-compliance-manometric test (TCM) assesses the passive and active tubal opening as well as the equilibration ability. The pressures necessary to open the eustachian tube (ET) are measured while performing the Valsalva maneuver and during swallowing (if needed with added pressure). The equilibration ability is also checked. Subjects with normal tympanometry were twice tested, at an interval of 1 to 2 weeks; 52 ETs (in 28 persons) entered the study. According to a variance analysis (ANOVA), there was no significant difference (alpha = 5%) between the two measurements (the results were time-independent). The mean opening pressures were 610 daPa (SD = 108) during the Valsalva maneuver and 97 daPa (SD = 40) during the swallow test. Nearly 14% of the tubes were considered floppy (unable to maintain a positive pressure). In order to study the influence of mucosal swelling on tubal function, 9 subjects (18 tubes) underwent a TCM before and after a nasal histamine provocation. The opening pressures in both tests were significantly altered (higher) after the provocation (ANOVA; 0.001 less than p less than 0.01). One tube became obstructed and two became floppy. The equilibration ability was not altered. The TCM proved to be of value as an easy, fast and quantitative test for assessing active and passive tubal function. PMID- 2239256 TI - [Benign cervical tumors of neuroectodermal origin: apropos of 3 clinical cases]. AB - Neuroectoblastic benign cervical tumors. Report of three clinical cases. Cervical neurogenic tumors are uncommon. They arise from the cranial nerves, the cervical sympathetic chain and the paraganglion cells of the parasympathetic system (non chromaffin cells). Three cases are reported (schwannoma-ganglioneuroma chemodectoma). The pertinent literature is reviewed for the classification, the diagnosis and the treatment. PMID- 2239258 TI - The puzzling success of allograft tympanoplasty. Possible immunological explanations. PMID- 2239257 TI - [Otological manifestations of leukemia. Apropos of a clinical case]. AB - The authors describe a clinical case of acute lymphoblastic leukemia, showing major leukemic infiltration of the cochlea and the acoustic nerve. The patient however didn't present any otological symptom. A brief literature review is added (clinical aspects, histopathological aspects ...). The authors stress on performing routine audiometric examinations in leukemia, especially in the acute forms of the disease. PMID- 2239259 TI - Empyema of a concha bullosa in a child with cystic fibrosis (case report). AB - An empyema of a concha bullosa or a middle turbinate pyocoele caused unilateral complete chronic nasal obstruction in an 8 year old girl affected by cystic fibrosis and was successfully operated. The possible pathogenetic mechanisms involved are reviewed and discussed. PMID- 2239260 TI - [An unusual cause of laryngeal stridor: the Shy-Drager syndrome]. AB - A case of laryngeal stridor in an adult patient is presented and the diagnose of syndrome of Shy-Drager is proposed. This syndrome is the result of a degeneration of the central nervous system. Some autonomic functions are involved in this process. The leading symptoms are an orthostatic hypotension, parkinson-like symptoms and laryngeal stridor. The last symptom results from a neurogenic paralysis of both posterior crico-arytenoideus muscles. A depletion of neurotransmitters in the central nervous system would be the cause of the syndrome. The treatment is symptomatic. Concerning the laryngeal stridor, tracheotomy, eventually followed by a crico-arytenoidopexy, is the only treatment which can be proposed. PMID- 2239261 TI - Vascularized temporoparietal fascial flap for closure of a nasal septal perforation. Report of a case. AB - The temporoparietal fascia is a thin, pliable and well-vascularized sheet of tissue available in large amounts. It is easily transferred to distant recipient sites by microvascular anastomosis or can be used as island pedicle flap. The fineness and flexibility of this flap, combined with the absence of sequelae at the donor site led us to use the fascia in a case for closure of a nasal septal perforation. PMID- 2239263 TI - Analysis of 185 submandibular gland excisions. AB - A review of 185 submandibular gland excisions over a ten year period is presented. The symptoms, physical findings, diagnosis on pathological examination and prognosis have been noted in each case to determine the incidence of neoplastic versus non-neoplastic disease. In our series non neoplastic disease of the submandibular gland was found in 141 patients (76%) with a large predominance of inflammatory lesion, while only 26 patients (14%) had a neoplastic lesion (6 benign lesions and 20 malignant tumors). There were also 18 (10%) patients surgically treated with gland excision for a glandular metastatic involvement from adjacent nodes. The significance of these findings is discussed. PMID- 2239262 TI - Possibilities in hypopharyngeal reconstruction--comparative study. AB - A comparative study between three types of hypopharyngeal reconstruction after laryngopharyngectomy is presented by evaluation of the following parameters: complications, duration of hospitalization and postoperative swallowing time. Each group contains the five most recently cases treated at the E.N.T. department of the K.U. Leuven. In recent years, the following types of hypopharyngeal reconstruction were used: the pectoralis major flap, the free radial forearm flap and the revascularized jejunum interposition. For reconstruction of circumferential hypopharyngeal defects after total laryngopharyngectomy, the jejunal graft presents hopeful results. PMID- 2239264 TI - Autonomic reflexes in preterm infants. AB - Some autonomic nervous reflexes often tested in adult medicine have been studied in 21 preterm infants (25-37 gestational weeks). The aim was to develop such tests for preterm infants and see if there were any differences in babies with recurrent apnea and bradycardia and babies who had been exposed to sympathicolytic drugs before birth. To test sympathetic nervous activity the peripheral vascular resistance was measured before and during 45 degrees of head up tilting. To test parasympathetic nervous activity the degree of bradycardia was measured in response to cold face test (application of an ice-cube on the fore-head) and laryngeal stimulation with saline. Finally the heart rate changes after a sudden noise (85 dB) were studied as an indicator of both sympathetic and vagal activity. The peripheral resistance was found to be relatively low in these preterm infants, particularly in some infants tested at the postnatal age of about two months. Heart rate and mean blood pressure did not change during tilting, while the peripheral resistance increased significantly mainly due to lowered limb blood flow. The median decrease of the heart rate during the cold face test was 20.0% and during laryngeal receptor stimulation 23.7%. The sudden noise usually caused a biphasic heart rate response. An autonomic nervous reflex score was calculated and found to be negative (parasympathetic) in infants with recurrent prolonged apnea and bradycardia and positive in infants with clinical signs of increased sympathetic nervous activity. PMID- 2239266 TI - Urinary and serum urea as indicators of protein metabolism in very low birthweight infants fed varying human milk protein intakes. AB - Urea concentrations in serum and urine were measured in 28 growing, very low birth weight, appropriate-for-gestational age infants fed varying human milk protein intakes (range 1.7 to 3.9 g/kg/day). We found a high correlation between serum urea values at the end of the study and mean protein intake (rs = 0.85, p less than 0.001) and between urinary urea concentrations in eight-hour urine collections and protein intake (rs = 0.81, p less than 0.001). All serum and urine urea values were below 1.6 and 18 mmol/l, respectively, at protein intakes less than 3 g/kg/day. Higher protein intakes caused higher serum and urinary urea concentrations. We also found a strong correlation between the individual serum and urinary urea values at the end of the study (rs = 0.90, p less than 0.001). The presented data are consistent with the growth data previously reported and indicate that inadequate or excessive protein intakes can be detected by measurement of urea concentrations in serum and/or urine. If urine urea samples alone can be used for estimating optimal protein intake, painful blood sampling procedures could be obviated. PMID- 2239265 TI - Concentration of twelve plasma proteins at birth in very low birthweight and in term infants. AB - Plasma samples obtained at birth from 70 very low birth weight (VLBW) infants (gestational age 24 to 34 weeks) and from 20 term infants were analysed for concentrations of 12 different proteins. The plasma concentrations of albumin, transthyretin (TTR), retinol-binding protein (RBP), vitamin D-binding protein, apolipoprotein A I, fibronectin, orosomucoid and alpha 1-antichymotrypsin were significantly lower in the VLBW infants than in the term infants, whereas the values of alpha-fetoprotein (AFP) were significantly higher in the VLBW infants. No differences were found between the two groups for apolipoprotein A II, apolipoprotein B and transferrin. Birth asphyxia and sex had no influence on the measured plasma protein concentrations. The plasma concentrations of apolipoprotein A I and A II were significantly lower in small-for-gestational age (SGA), VLBW infants compared with appropriate-for-gestational age (AGA), VLBW infants. Possible acute inflammation (defined as raised concentrations of orosomucoid or alpha 1-antichymotrypsin) was associated with significantly higher values of vitamin D-binding protein in both VLBW and term infants, suggesting that this protein may act as an acute phase protein in newborn infants. PMID- 2239267 TI - Suboptimal mineral composition of cow's milk formulas: a risk factor for the development of late metabolic acidosis. AB - Late metabolic acidosis was observed in a term baby boy with renal tubular acidosis type 4 who received two cow's milk formulas in succession. Suboptimal mineral composition of the formulas turned out to be an important risk factor for the development of late metabolic acidosis. PMID- 2239268 TI - Immediate effects on lung function of instilled human surfactant in mechanically ventilated newborn infants with IRDS. AB - We have studied the effects on lung volume, respiratory mechanics and ventilation during the first hours after instillation of 60 mg/kg of human surfactant into the trachea of 4 very preterm, newborn infants with severe IRDS under mechanical ventilation. Measurements were made with a "face-out" body plethysmograph and a modified nitrogen wash-out method. In addition to a transient decrease in total and alveolar ventilation immediately after the instillation we found an immediate rise in lung volume, but respiratory compliance decreased. These changes lasted less than two hours. Oxygen requirements fell in 3 out of 4 infants. The changes in lung volume and compliance are explained in terms of changes in the shape of the static recoil pressure characteristics of the diseased lungs after treatment. Mechanisms behind the short duration are sought in mode of instillation, dosage, age at treatment, and severity of disease. PMID- 2239269 TI - Myocardial dysfunction and cerebral blood flow velocity following birth asphyxia. AB - Birth asphyxia often leads to left ventricular myocardial dysfunction. To assess the effect of myocardial dysfunction on cerebral perfusion, we evaluated cardiac output and cerebral blood flow velocity in the anterior cerebral and internal carotid arteries in 20 asphyxiated term newborn infants during the first 4 days of life using 2-dimensional/pulsed Doppler ultrasound. In 8 infants with myocardial dysfunction cardiac output was reduced on days 1 and 2 and within normal limits thereafter. In these infants changes in mean cerebral blood flow velocity and pulsatility index were passively related to changes in mean arterial pressure and cardiac output. In 12 infants without myocardial dysfunction a stable cerebral blood flow velocity pattern was found, which was unaffected by changes in mean arterial pressure. We conclude that infants presenting with a reduced cardiac output after deliveries associated with severe asphyxia may be at risk for additional ischemic or hemorrhagic cerebral damage because of lack of autoregulation. PMID- 2239270 TI - Red cell phosphate metabolism in preterm infants with idiopathic respiratory distress syndrome. AB - Phosphate metabolism was studied in twenty-one preterm infants with idiopathic respiratory distress syndrome during and after oxygen (O2) therapy using a hood. Plasma, red cell inorganic phosphate (Pi) and the red cell concentrations of organic phosphate metabolites ATP and 2,3-diphosphoglycerate were significantly lower in the sick infants when compared to controls of similar age and birthweight, and remained low even 24 h after cessation of therapy. Plasma cortisol levels were elevated at the onset of the disease and decreased to almost control levels by the end of O2 therapy while the values of plasma calcitonin did not show any difference from controls. Plasma creatinine phosphokinase and blood lactic acid levels followed the pattern of the control group with a small increase at the beginning of the study and decreasing thereafter. Several factors may be implicated in the cause of hypophosphatemia in these infants such as inadequate feeding, acidosis and hypercortisolaemia due to stress leading to phosphaturia. PMID- 2239271 TI - The value of neonatal serum thyroglobulin determinations in the follow-up of patients with congenital hypothyroidism. AB - Serum thyroglobulin was determined in 68 newborn infants with positive screening tests for congenital hypothyroidism. In 38 infants the diagnosis was confirmed (patients), but the remaining 30 were euthyroid at follow-up (controls). The mean thyroglobulin concentration at the age of 2 weeks did not differ significantly between the patients and the controls (179 vs. 125 micrograms/l). Thyroid scintigraphy was performed in 15 patients. All seven with thyroid aplasia, based on 99mTc pertechnetate scintigraphy, had measurable thyroglobulin (greater than 2 micrograms/l) and thyroid hormones in their serum. This indicates that total absence of thyroid tissue is very rare in Swedish patients with congenital hypothyroidism. Scintigraphy based on 99mTc does not permit detection of small amounts of thyroid tissue. The neonatal concentrations of thyroglobulin did not correlate with the results of Griffiths test at 3 years and are therefore not useful for prognosis of psychomotor development. We conclude that neonatal measurement of thyroglobulin is of limited value in the follow-up of patients with congenital hypothyroidism. PMID- 2239272 TI - Prediction of final height in Turner's syndrome. A comparative study. AB - Various methods are used for prediction of final height in girls with Turner's syndrome (TS), but their accuracy has not been systematically investigated or compared. We have compared predictions of final height made with the most commonly used methods in 20 Turner girls at ages 9.5-18 years. Growth standards based on growth and final height of 78 Danish Turner women were used for calculation of standard deviation scores (SDS). In order to provide the necessary basis for "index of potential height" (IPH) method, bone age development was determined from 74 X-rays of 38 untreated Turner girls aged 5.2-19 years. This method was further modified and improved for use in TS. Prediction methods based only on height and chronological age (CA) showed little difference from methods including bone age. The IPH method in our modification was more accurate than those of Bayley-Pinneau and Tanner. At younger ages the IPH method showed better results when using Tanner-Whitehouse 2 (TW2) bone age than when using Greulich Pyle bone age. Accuracy of predictions were considerably improved by combining methods with and without allowance for bone age. Combinations including the IPH method based on TW2 bone age appeared to be the most accurate. Predictions of final height in Turner's syndrome should therefore be made by combining the IPH method and one of the methods based on height and CA. PMID- 2239273 TI - Effect of oxandrolone on growth and final height in Turner's syndrome. AB - Thirty-two girls with Turner's syndrome aged 11.5-16.7 years were treated with oxandrolone (0.125 mg/kg/day). The treatment period was scheduled to 2 years. Height velocity (HV) was expressed in Standard Deviation Scores (SDS), calculated by growth standards for untreated Danish Turner-girls. For girls with initial bone age below 13 years HV increased significantly from a mean pretreatment value of -0.2 SDS (3.1 cm/year) to +3.5 SDS (5.6 cm/year) in the 1st year of treatment and +2.1 SDS (4.1 cm/year) in the 2nd year. Mean bone age velocity during treatment was 0.9 year/year. Twenty-two girls have reached final height. Predictions of their final height were made by three different methods and compared to observed final height. A significant (p less than 0.001) improvement in the order of 3-4 cm was found for girls with initial bone age below 13 years, while girls with higher initial bone age had no height gain (p greater than 0.3). Side effects were seen in 16% of the girls. PMID- 2239274 TI - Neurosecretory dysfunction of growth hormone secretion in thalassemia major. AB - The growth retardation of children with thalassemia major is multifactorial. Along the endocrine axis of growth hormone (GH), serum somatomedin has been shown to be deficient and GH response to GH-releasing hormone impaired, while GH response to provocative stimuli is normal. We studied the spontaneous secretion of GH in seven patients with thalassemia major and growth retardation. Three of the patients were hypothyroid, and the other four were euthyroid. Spontaneous secretion of GH in all seven patients was subnormal: the number of pulses, the mean pulse amplitude, and the integrated concentration of GH were all lower than in 14 age- and sex-matched (10 pubertal and 4 prepubertal) control subjects. GH response to provocative stimuli was normal in the euthyroid patients. This pattern of response corresponds with the definition of neurosecretory dysfunction of GH secretion. It is concluded that the growth retardation of patients with thalassemia major is partly due to neurosecretory dysfunction of GH secretion. PMID- 2239275 TI - Growth and growth hormone therapy in hypochondroplasia. AB - The growth of 84 patients with hypochondroplasia (56 male, 28 female) was studied. A wide spectrum of severity was found from quite severe short limbed dwarfism to short apparently normal prepubertal children who manifested disproportion only at puberty when growth failed. The onset of puberty was at the normal time but the pubertal growth spurt appeared not to materialize and it is this lack which resulted in severely compromised adult heights of 145-165 cm in boys and 133-151 cm in girls. Twenty (12 M, 8 F) hypochondroplastic children aged between 4.3 and 12.8 years were recruited to a study of the effects of biosynthetic growth hormone. All had normal growth hormone responses (greater than 15 mU/l) to a pharmacological test of growth hormone secretion. Biosynthetic growth hormone in doses between 12-32 mu/m2/week produced a significant acceleration in height velocity standard deviation score (SDS) for chronological age (CA) from a pretreatment mean of -1.66 (SD 1.36) to +1.62 (SD 1.52) (p less than 0.001). Significant increases were also observed in the height SDS for bone age (BA), sitting height (SH) SDS and subischial leg length (SILL) SDS. A longer period will be required to assess the effect of treatment on adult height prognosis. PMID- 2239276 TI - Anticardiolipin response in Kawasaki disease. AB - Antibodies against cardiolipin are formed in many different infectious diseases, and high levels are associated with susceptibility to thrombosis, especially in patients with systemic lupus erythematosus. In view of the postulated infectious etiology of Kawasaki disease an its association with thrombosis, we have studied the occurrence of anticardiolipin antibodies in this disease. Serial serum specimens from 36 patients were tested, using a solid-phase enzyme immunoassay. A change of at least 0.3 optical density units between two consecutive specimens for at least one immunoglobulin class was observed in 47% of cases. Peak levels occurred one to two weeks after the onset of symptoms. Four patients developed coronary artery aneurysms, and they all showed a clear anticardiolipin response. Anticardiolipin antibodies might be one factor contributing to coagulation abnormalities in patients with Kawasaki disease. PMID- 2239277 TI - Increased interleukin-1 (IL-1) production from LPS-stimulated peripheral blood monocytes in children with febrile convulsions. AB - Peripheral blood mononuclear cells (MNC) from 27 children with a febrile convulsion were tested for production of interleukin-1 (IL-1) in culture. MNC stimulated with lipopolysaccharide (LPS) showed a significantly increased production of IL-1 when compared to MNC from children without convulsions but with bacterial infections (p less than 0.001), viral infections (p less than 0.005) or no infection (p less than 0.005). Children who had experienced a febrile convulsion were retested several months later; this time the IL-1 production from LPS-stimulated MNC was not different from controls. These results demonstrate that MNC at the time of febrile convulsions have increased sensitivity to LPS and possibly to other IL-1 inducers; the resulting enhanced IL 1 response from sensitized MNC may have a role in the pathogenesis of febrile convulsions. PMID- 2239278 TI - Growth after treatment of solid tumours in childhood. AB - We examined 90 survivors of childhood solid tumours diagnosed in our hospital between 1960 and 1976. Their ages at the time of this study ranged from 12.2 to 41.5 years. Adult standing height was usually normal. However, final standing height was less than expected in the females, and sitting height was below the normal mean in the males. The males who had received both chemotherapy and radiation therapy to the spine had a greater decrement in sitting height, but we did not find any association between radiation therapy to the spine without chemotherapy and subsequent total growth of the spine as measured by sitting height. We conclude that these children generally do not experience any major growth disturbances. PMID- 2239279 TI - Fibrosing alveolitis in childhood. A long-term follow-up. AB - A retrospective analysis of 14 pediatric cases with fibrosing alveolitis, proved by lung biopsy, was carried out. The children were initially 6-16 years old (mean: 9.8 years) and were observed for 2 to 7 years. Symptoms had been present prior to diagnosis for 1 to 156 weeks (median: 11 weeks). The most prominent clinical findings were dyspnoea (100%), dry cough (91%), tachypnoea (85%), and weight loss (70%). Open (n = 9) or transbronchial (n = 5) lung biopsy specimens had predominantly cellular appearances in 8 children (group A) and showed predominantly fibrotic changes in 6 cases (group B). Lung function tests revealed a marked ventilatory impairment in all children. Mean vital capacity was 44% (SD 16%), and total lung capacity 58% (SD 14%) of the predicted normal values. Specific lung compliance was significantly lower in children with fibrotic changes (mean: 0.016 vs. 0.030 ml/cmH2O/ml in patients of group A, p less than 0.05). Results from 200 lung function measurements were evaluated during the follow-up. Corticosteroid treatment improved vital capacity in all children after 6 and 12 months of treatment to 64% and 62% of the predicted normal, respectively. Deterioration of pulmonary function was observed in 7 children when prednisone was tapered to below 10 mg per day. Only 4 children had a normal vital capacity at their last visit to the clinic. We conclude that children with fibrosing alveolitis experience severe alterations in lung function, and that the overall outlook is quite unfavorable. PMID- 2239280 TI - The course of biological parameters and 6-mercaptopurine pharmacokinetics during maintenance treatment of children with acute lymphoblastic leukaemia. AB - Twenty patients on maintenance therapy (MT) for acute lymphoblastic leukaemia (ALL) with oral 6-mercaptopurine (6-MP) and methotrexate (MTX) were studied. White cell and red cell indices and platelets counts were monitored every second week as were drug levels. Mean values for 6-MP and MTX doses, and blood component parameters were calculated for each 6-month period for the whole patient group. 6 MP plasma concentrations and liver-function tests were determined once every six months and mean values calculated. 6-MP and MTX mean doses did not change significantly during MT. The mean area under the concentration versus time curve (AUC) 0-4 hours varied slightly from the start to the end of the MT (257 and 296 ng/ml.h, respectively). The mean plasma peak concentration increased from 98 ng/ml to 195 ng/ml (p less than 0.01) during the same period. There were significant decreases between the initial white blood cell counts (WBC) and red blood cell counts (RBC) as compared to levels at the end of therapy (p less than 0.01 and 0.02, respectively). A linear correlation was found between 6-MP peak concentrations and both WBC (r = 0.96) and RBC (r = 0.87). At the end of MT liver function tests became normal in all except 6 patients. In conclusion, MT have moderate effects on bone marrow and liver and monitoring 6-MP plasma concentration might be of value for determination of the optimal WBC levels during MT. PMID- 2239281 TI - Use of medical care and antibiotics among preschool children in different day care settings. AB - The use of medical care among 880 1-5 year olds in different day care settings was studied using register information on physician visits, purchases of antibiotics and municipal day care in 1984. The unit of analysis was months in the different day care settings and not children. The rates of physician visits were 1.4 to 1.8 times higher for acute upper respiratory tract infections and all acute infections and 2 to 3 times higher for secretory otitis media during day care centre months and family day care months as compared to home care months. The rate of visits for bronchial asthma was 5 times higher during day care centre months than during home care months. No differences were found between day care centre months and family day care months with respect to the rates of physician visits for acute upper respiratory tract infections, acute otitis media and all acute infections. Among children in family day care, the daily number of hours in day care, and size, average age and age homogeneity of the groups were not significantly associated with rates of visits for all acute infections or purchases of antibiotics. PMID- 2239283 TI - Central venous catheter insertion in neonates. PMID- 2239282 TI - Acute alcohol intoxications in children treated in hospital. AB - Cases of alcohol intoxication in children are common; they are encountered every day in Finland. Studies other than case studies of alcohol intoxication in children are few. Metabolic acidosis was a frequent finding in juvenile alcohol intoxication. Capillary or arterial blood pH was below normal (less than 7.36) in 61.4% of patients and bicarbonate (less than 22) in 55.3% of patients. pCO2 was varied; the higher the blood alcohol concentration the higher the pCO2. Metabolic acidosis and blood pH correlated with the blood alcohol concentration and consciousness. The lower the blood pH the higher the serum glucose. Hypoglycemia is the most common reported symptom in children under 5 years of age. In the present study three patients were slightly hypoglycemic. Hypokalemia was the most important change (in 12.2%) in serum electrolytes. Alcohol intoxication causes metabolic acidosis and respiratory depression in children. Metabolic acidosis reduces consciousness. PMID- 2239284 TI - Vascular air embolism--possible survival. PMID- 2239285 TI - Comment on C3d generation in septicaemic newborns. PMID- 2239286 TI - The shape of a child: is it normal or abnormal? PMID- 2239288 TI - Sex-related differences of bone mineral content in low birthweight infants fed cow's milk formula. PMID- 2239287 TI - Protein requirement may correlate to postconceptional age and not birthweight in very low birthweight infants. PMID- 2239289 TI - Ocular findings of Williams' syndrome. PMID- 2239290 TI - Use of a long acting somatostatin analogue in controlling ileostomy diarrhoea in infants. PMID- 2239291 TI - Reduced plasma carbamazepine level during chemotherapy in a child with malignant lymphoma. PMID- 2239292 TI - Necrotizing bowel disease with candida peritonitis following severe neonatal hypothermia. AB - Peritonitis due to Candida albicans is rare in the newborn infant. Three low birthweight, extremely ill premature infants who were severely hypothermic at the time of admission developed perforation of the gastrointestinal tract. C. albicans was cultured from the peritoneal fluid in each case. In view of the rareness of C. albicans peritonitis in newborns, this cluster of infants suggests a relationship between severe neonatal hypothermia, and bowel perforation with peritonitis due to this fungus. PMID- 2239294 TI - Child abuse. PMID- 2239293 TI - Children with epilepsy as adults: outcome after 30 years of follow-up. AB - The study dealt with a representative sample of the epileptic population in southwestern Finland, followed up prospectively for 23-39 years. At the end of the follow-up period, 55.5% of the original sample, i.e. 63.2% of the subjects who participated in the last follow-up evaluation, or 76.4% of those who were alive at that time, had not had epileptic attacks for at least the previous three years. A total of 60% lived independently; 21% of subjects, on the other hand, were not gainfully employed and lived in institutions. The intermediate group was the smallest (less than 18%); these were receiving a disability pension but had not been institutionalized. A certain polarization thus seemed to take place here: the epileptic patient either lead a normal life or was in institutional care. The intermediate group showed a steady decline in size in the course of the follow-up. PMID- 2239295 TI - The morbid anatomy of the human genome: the role of gene mapping in clinical medicine. PMID- 2239296 TI - Antioxidant enzymes and lipoperoxide in blood in patients with Kawasaki disease. Comparison with the changes in acute infections. AB - Increased production of active oxygen species from activated neutrophils is postulated to contribute to endothelial damage in Kawasaki disease, leading to the formation of coronary aneurysms. To determine whether an altered oxidant antioxidant balance exists in acute phase of Kawasaki disease, antioxidant enzymes in peripheral blood cells and plasma lipid peroxide were measured in patients. The two isoenzymes of intracellular superoxide dismutase were assayed by specific radioimmunoassays. Lipid peroxide in plasma and manganese superoxide dismutase in both polymorphs and lymphocytes were increased in the acute phase of Kawasaki disease. The erythrocyte glutathione peroxidase and catalase were also increased. On the other hand, copper zinc superoxide dismutase in polymorphs, lymphocytes and erythrocytes was unaltered. Acute infections did not appear to modify the levels of either antioxidant enzymes or lipid peroxide in blood. These results suggest that increased oxidative stress in Kawasaki disease evokes a reactive increase in antioxidant enzymes, and that this response in the defense system is related to the reversible nature of the tissue damage in most patients with Kawasaki disease. PMID- 2239297 TI - Serum levels of glycated albumin in non-diabetic and insulin-dependent diabetic children. AB - The serum levels of glycated albumin (GA) in 83 non-diabetic children and 26 children with insulin-dependent diabetes mellitus (IDDM) were measured by high performance liquid chromatography (HPLC). In non-diabetic children over one year, the GA levels were found to be uninfluenced by age, while the fructosamine (FRA) levels increased with age. The mean level of GA in IDDM children was 39.1 +/- 9.1%, which was significantly higher than in non-diabetic children with values of 16.1 +/- 1.1% (p less than 0.01). The GA levels of non-diabetic and IDDM children did not overlap, whereas their FRA levels did overlap. The GA levels correlated with HbAlc levels (r = 0.74, p less than 0.01) and FRA levels (r = 0.66, p less than 0.01) in IDDM children. The GA levels were more closely correlated than the FRA levels with the blood glucose two and three weeks previously. Thus, the GA level is a useful indicator of short-term control in diabetes mellitus. PMID- 2239298 TI - Urinary dicarboxylic acids in X-linked adrenoleukodystrophy. AB - The urinary excretion of dicarboxylic acids in X-linked adrenoleukodystrophy (X ALD) was studied. The dicarboxylic acid profile in X-ALD did not show any specific pattern, unlike Zellweger syndrome and neonatal adrenoleukodystrophy. Medium-chain dicarboxylic acids with an even number of carbon atoms (adipic, suberic, sebacic) and an odd number of carbon atoms (pimelic, azelaic) were excreted within the normal ranges. Dicarboxylic acids with more than 10 carbon atoms were not found. These findings may be due to the normal beta-oxidation system of dicarboxylic acids in X-ALD. PMID- 2239299 TI - Flowcytometric analysis of DNA pattern of cells derived from xeroderma pigmentosum A--hypersensitivity to vincristine, etoposide and methotrexate. AB - Xeroderma pigmentosum complementation group A (XPA) is one of the DNA repair deficient syndromes. The cell biological features of XPA were examined by flowcytometry using Epstein Barr (EB) virus-transformed lymphoblastoid cells. Cellular sensitivity to vincristine (VCR), etoposide (VP-16) and methotrexate (MTX) were assayed by DNA pattern changes by flowcytometry. Recently, ataxia telangiectasia (AT), one of the same kind of disorder, has been reported to have an increased sensitivity to VCR and VP-16. However, AT showed some resistance to MTX according to other reports. Our results showed that XPA had an increased sensitivity to VCR and also to VP-16. Moreover, different from AT, XPA showed some sensitivity to MTX. Thus there is some cell biological similarity between XPA and AT, as well as some difference of the abnormality in the DNA repair pathway. PMID- 2239300 TI - Prevalence of Paragonimus westermani in some Ulchin school children. AB - In order to estimate the prevalence of Paragonimus westermani among the school children in Ulchin county, Kyungpook Province, five primary schools were selected for sampling. The children were first examined using an intradermal test with Paragonimus antigen, Lot No. 890417, and then examined for Paragonimus eggs from sputa and stools collected from the intradermal-positive cases. In a total of 382 children examined, 53 cases or 13.9 percent revealed positive reactions for Paragonimus westermani. The sex specific rate of infection was a little higher in boys than in girls. The age specific rate of Paragonimus westermani infections varied from age to age. Paragonimus westermani was most prevalent in the 8-year old group in both sexes and showed about the same proportion among boys and girls of each age group. A comparison of the reliability for the detection of Paragonimus eggs from intradermal positive cases in this study showed that the sputum test was more sensitive than the stool test. Summarizing the results, this study indicates that the prevalence for Paragonimus westermani is still high and the endemic foci of the fluke exists in Ulchin county, Kyungpook Province, Korea. PMID- 2239301 TI - Relation between blood pressure, left ventricular mass and pulsed Doppler parameters in healthy school children. AB - We analyzed the relations between blood pressure in sitting and supine positions, left ventricular mass (LVM) and Doppler aortic, pulmonary and mitral flow velocity measurements in 163 healthy school children. Systolic blood pressure in a supine position correlated significantly with aortic acceleration (ATc) and ejection time (ETc), corrected by the square of R-R interval, pulmonary AT and peak flow velocities. Moreover, the systolic blood pressure in a sitting position correlated with pulmonary AT and LVM. LVM correlated with pulmonary ATc, the ratio of AT to ET and average acceleration, and aortic ETc and peak flow velocity. These data suggest the following: (1) the posture influences the relation between blood pressure and flow velocity, (2) pulmonary hemodynamics are influenced by systemic blood pressure in healthy children and (3) the development of LVM may be dependent not only on blood pressure but also on cardiac work in childhood. PMID- 2239302 TI - Changes of left ventricular isovolumic relaxation time with growth in children. AB - We investigated the changes of left ventricular isovolumic relaxation time (LVIRT) with growth and the factors influencing them during childhood, in a 10 year follow-up study. We measured the body height (BH), body weight (BW), lean body weight (LBW), heart rate (HR), blood pressure (BP), left ventricular muscle volume index (LVMVI), and LVIRT corrected by the preceding R-R interval (IRT/R R), of 187 healthy children at 3-year intervals (6, 9, 12, 15 years old). IRT/R-R were prolonged with growth in boys and girls. At the ages of 12 and 15, the IRT/R R of girls were longer than those of boys. Significant correlation coefficients for IRT/R-R on systolic and diastolic, BW, and LVMVI were 0.28, 0.31, 0.20, 0.28, respectively. These data suggest that (1) IRT/R-R is mainly determined by the diastolic BP, (2) left ventricular diastolic function of children develops with growth of body size, especially BW, and (3) left ventricular early diastolic function in adolescents is related to sexual maturation. PMID- 2239303 TI - Treatment of pediatric malignant tumors with VP-16. West Japan Pediatric Oncology Group. AB - The West Japan Pediatric Oncology Group studied the treatment of pediatric malignant tumors with VP-16 from December 1984 to March 1988. Study subjects were divided into two groups. One group received only VP-16, while the other received VP-16 combined with other anti-tumor agents. VP-16 evaluation was possible in a total of 116 cases. The efficacy rate was calculated by considering both complete and partial remission as effective. The efficacy rate for VP-16 alone was 87.5% for primary cases of ANLL and 100% for primary cases of histiocytosis. The efficacy rates for combination therapy were as follows: 92.6% for primary cases of ANLL, 66.7% for primary cases of histiocytosis, 45.5% for relapsed cases of ANLL and 66.7% for relapsed cases of ALL. Bone marrow suppression was seen in the form of leukopenia and thrombocytopenia for 2 to 3 weeks after VP-16 administration. Alopecia, mucositis and gastrointestinal symptoms were also observed, but they presented no significant problem. From our results, we believe that chemotherapy including VP-16 is effective for remission induction therapy in primary cases of ANLL and for salvage therapy in relapsed leukemia. Additionally, VP-16 is considered to be effective for the treatment of histiocytosis. PMID- 2239304 TI - Ectopic nesidioblastosis. AB - We observed one case of ectopic nesidioblastosis. A solitary nesidioblastoma was observed in the anterior wall of the duodenum. Ectopic nesidioblastosis has not been previously reported, but our experience suggests the necessity of examination for ectopic pancreas in cases of SIDS or its near-miss. PMID- 2239305 TI - Pernicious anemia in a patient with hypogammaglobulinemia. AB - A 19-year-old male with pernicious anemia and hypogammaglobulinemia (common variable immunodeficiency: CVID) is reported in comparison with classical pernicious anemia. This case was characterized by an earlier onset of anemia, the absence of autoantibodies to intrinsic factor or gastric parietal cells and involvement of the pyloric antrum as well as the gastric corpus. It is suggested that dysregulation of cellular immunity produces the autoimmune lesion in the gastric mucosa, including the pyloric antrum, in a patient with CVID, and that some of such cases develop pernicious anemia. PMID- 2239306 TI - Intrauterine Chlamydia trachomatis infection in a premature infant. AB - Intrauterine Chlamydia trachomatis infection was strongly suspected in a premature infant born in the 32nd week of gestation. The membranes were artificially ruptured at the time of delivery. This infant showed a high titer of specific IgM antibody to Chlamydia trachomatis at one hour after birth. He showed mild respiratory distress and was treated with oral erythromycin for three weeks. He was discharged home at the age of 46 days. PMID- 2239307 TI - Detection of C. trachomatis by in situ DNA hybridization: report of two cases with neonatal pneumonia. PMID- 2239308 TI - Therapeutic benefit of growth hormone in achrondroplastic dwarfism. PMID- 2239309 TI - Echocardiography may be misleading in assessing coronary sequelae of MCLS: a CT scan helps. PMID- 2239310 TI - Uptake of immunization of children with asthma. PMID- 2239311 TI - Acute phenobarbital intoxication in an infant. PMID- 2239312 TI - Influence of timing of administration of liposome-encapsulated superoxide dismutase on its prevention of acetaminophen-induced liver cell necrosis in rats. AB - The possible participation of acute oxidative stress in the in vivo mechanism by which acetaminophen (APAP) induces hepatocellular injury was examined. Male Sprague-Dawley rats were administered 3-methylcholanthrene, fasted for 18 h, then given APAP and sacrificed after a further 6 h of fasting. Extensive centrilobular liver cell necrosis along with markedly elevated serum activity of aminotransferases was observed. Liposome-encapsulated human recombinant Cu-Zn superoxide dismutase (LSOD) administered 1 or 0.5 h prior to APAP or simultaneously with the toxin completely prevented APAP-induced hepatocellular injury. In contrast, LSOD administered 5 or 2.5 h before or 1, 2.5 or 5 h after the toxin treatment did not prevent APAP toxicity. Incomplete protection against APAP-induced injury was obtained when LSOD was administered 0.5 h after the toxin. These results support the proposal of an oxidative mechanism for APAP hepatotoxicity. PMID- 2239313 TI - Expression of vimentin and epithelial membrane antigen in human malignant lymphomas. AB - Immunoreactivity with monoclonal antibodies against the intermediate filament protein, vimentin, and epithelial membrane antigen (EMA) was examined in 330 cases of lymphoma (317 non-Hodgkin's and 13 Hodgkin's lymphomas), 12 reactive lymph nodes and mononuclear cells of the peripheral blood using either indirect immunoperoxidase staining or the avidin-biotin immunoperoxidase complex technique. The cell origin of each tumor was established using a panel of monoclonal antibodies against lymphocyte differentiation antigens. There were 41 T-cell, 247 B-cell and 29 undetermined lymphomas, and 13 cases of Hodgkin's disease in the series. Vimentin was expressed in 24 T-cell lymphomas (58.5%) and 60 B-cell lymphomas (24.2%). This difference in frequency was statistically significant. Vimentin expression in follicular lymphomas was less frequent than in diffuse B-cell lymphomas. In diffuse lymphomas, small and medium cell types were more reactive with anti-vimentin than large cell types. Reed-Sternberg cells (R-S cells) in Hodgkin's disease were positive for vimentin in 11 cases (84.6%). The frequency of EMA reactivity in lymphomas was low, particularly in T-cell lymphomas. No positive cases were found among follicular lymphomas. In diffuse non-Hodgkin's lymphomas, EMA was expressed only in mixed and large cell types, but never in smaller ones. In conclusion, monoclonal antibodies against vimentin and EMA appear to be of limited usefulness for the diagnosis of non-Hodgkin's lymphomas, but anti-vimentin antibody may be used as an adjunct to the diagnosis of R-S cells in Hodgkin's disease. PMID- 2239315 TI - Juvenile granulosa cell tumor in a three-year-old infant. An immunohistochemical and ultrastructural study. AB - A three-year-old female infant with a juvenile granulosa cell tumor of the ovary and precocious pseudopuberty is presented. Laboratory tests revealed elevated levels of serum and urinary estrogen. Histological examinations showed an immature follicular pattern surrounded by theca-like stromal tissue. The immunohistochemical localization of estradiol, estriol, progesterone and testosterone was studied by indirect immunoperoxidase staining of cryostat sections. All of these steroid hormones were localized mainly in stromal cells and in some follicular cells. Electron microscopic examination revealed three types of tumor cell, i.e. polygonal cells, spindle cells and transitional cells. Well developed smooth endoplasmic reticulum, mitochondria with tubulovesicular cristae, and lipid droplets in the cytoplasm, which are typical features of steroid synthesis, were conspicuous mainly in the last type of cell. Such transitional cells almost corresponded to steroid-positive cells. These cells were considered to have a close relationship to theca gland cells of developed ovarian follicles and to have mainly participated in steroid synthesis in the present tumor. In addition, some spindle cells showed features of myofibroblasts, such as intracytoplasmic filaments, dense body-like structures, and pinocytotic vesicles. These features suggest that the cells might all be derived from the same progenitor of ovarian mesenchyme. PMID- 2239314 TI - Lung carcinoma metastatic to microfollicular adenoma of the thyroid. A case report. AB - A 75-year-old woman with lung adenocarcinoma in whom autopsy revealed metastasis to microfollicular adenoma of the thyroid is described. A thyroid tumor specimen from this patient was initially interpreted as representing primary encapsulated follicular carcinoma of the thyroid associated with a component of poorly differentiated carcinoma of follicular cell origin. The widespread involvement of the lungs and other sites was also interpreted as metastases from the poorly differentiated carcinoma component within the encapsulated follicular carcinoma of the thyroid. Subsequent meticulous histologic examination revealed that the thyroid tumor was a microfollicular adenoma, and that the component of poorly differentiated carcinoma within it was the same as the lung carcinoma. Immunohistochemical investigation revealed that the poorly differentiated carcinoma cells within the thyroid tumor were stained positively with polyclonal and monoclonal antibodies against carcinoembryonic antigen (CEA) and negative for thyroglobulin and calcitonin. The carcinoma cells from the lungs and other sites also showed positive staining for CEA. These findings support the view that the component of poorly differentiated carcinoma was a metastatic lesion from the primary lung carcinoma to the microfollicular adenoma of the thyroid. The present study emphasizes that attention should be directed to thyroid metastasis, even if it is within a thyroid primary neoplasm. PMID- 2239316 TI - [Synthesis of catechol aminoketone and its analogues]. AB - In this paper, the synthesis of a series of aminoketone derivatives are reported. Compounds I1-9 and II1-10 were synthesized from substituted chloroacetophenone with various amines. Compounds I10-12 and II11-12 were synthesized from substituted acetophenones with corresponding amines through Mannich reaction. The 1HNMR and MS were discussed. Pharmacological study showed that the vascular contraction of dog mesenteric and basilar arteries induced by serotonine and calcium in vitro could not be antagonized by this kind of compounds and the known compound 3,4-dihydroxy acetophenone (I0). Except I10, the vasodilator effects of all compounds as shown by measurement of arterial blood flow after injection into femoral artery in dogs are weaker than I0. After intravenous injection in anesthetized dogs, I10 showed the same effect as I0 to increase coronary blood flow and myocardial contraction. Furthermore, the ventricular arrhythmia induced by aconitine and chloroform could also be protected by compound I10, but compound I0 was not effective. PMID- 2239317 TI - [Mass spectrometric studies on dibenzocyclooctadiene lignan compounds from Schisandraceae plants]. AB - Mass spectrometric studies on fragmentation patterns of 23 dibenzocyclooctadiene lignan compounds isolated from Schisandraceae plants, such as schisandra A (1), were carried out by using low and high-resolution mass spectrometric techniques and metastable ion analyses. The main mass spectral characteristics were summarized to provide a sound basis for further researches on Schisandraceae plants and for structural elucidation of similar new compounds. PMID- 2239318 TI - [Structure of swertiamacroside from Swertia macrosperma C.B. Clark]. AB - From the air-dried whole plant of SwerBia macrosperma C. B. Clark four compounds I-IV were isolated. One of them is a new caffeic acid disaccharide ester. Its structure was elucidated as 1-O-trans-caffeoyl-6-O-alpha-L-rhamnopyranosyl-beta-D glucopyranos ide, i. e. trans caffeic acid-1-O-rutinose ester on the basis of chemical and spectroscopic analysis, and named swertiamacroside (I). The other three known compounds were identified as mangiferin (II), bellidifodin (III) and bellidifodin-8-O-beta-D-glucopyranoside (IV). PMID- 2239319 TI - [Structure of pingbeimine C]. AB - A new C-nor-D-homosteroid alkaloid, C27H43O6N, mp 171.5-173 degrees C, named pingbeimine C, was isolated from the bulb of Fritillaria ussuriensis Maxim. On the basis of IR, MS, 1HNMR and 13CNMR spectroscopic data, particularly X-ray crystallographic analysis, structure IV has been assigned to this alkaloid. PMID- 2239320 TI - [Reverse-phase HPLC determination of coumarins in the traditional Chinese drug bai-zhi (Angelica dahurica forma bai-zhi)]. AB - A reversed phase HPLC procedure has been developed for the separation and determination of oxypeucedanin (I), imperatorin (II) and isoimperatorin (III) in Bai-zhi simultaneously. I, II and III were extracted from Bai-zhi by using ether. The solution was evaporated to dryness and the residue was redissolved in 25 ml of ethyl acetate and 10 microliters of the solution were analysed on Waters mu Bondapak C13 column (300 x 3.9 mm ID) using methanol-water (70:30) as the mobile phase and detecting at 254 nm. The results were calculated by external standard method on the basis of peak area. The average recoveries of the standards added to the sample were 101.36, 100.54 and 97.91% for I, II and III respectively, and coefficients of variation were less than or equal to 3.33%. Analytical results by HPLC method are in agreement with those by TLC method. This method is rapid, reproducible and accurate and has been applied to analyse the contents of three components in 42 samples of angelica. The results of fourteen samples were given. PMID- 2239321 TI - [Application of ridge regression spectrophotometry to the determination of multicomponents in aspirin compound tablet]. AB - In this paper, a ridge regression method of spectrophotometry in multiwavelength is proposed. The basic principle and computing of this method applied to multicomponent analysis were discussed. This method was applied to simultaneous determination of multicomponents in aspirin compound tablet and satisfactory results were obtained. The experiment clearly indicates that ridge regression may provide a new approach to experimental measurement of multicomponent analysis computations. PMID- 2239322 TI - [Study on prolonged action cefotoxime]. AB - A prolonged action cephalosporin was prepared by the reaction of cefotaxime sodium (CTX) with N,N-dibenzylethylene diamine acetate. It is reasonable to consider the resultant as benzathine cefotaxime (BCTX) by means of elemental analysis, DSC, UV spectra, IR spectra, NMR spectra and mass spectra. In contrast to CTX, BCTX appeared to be almost insoluble in water and its intrinsic dissolution rate was 0.183 micrograms/ml.min. The stability revealed that the degradation of BCTX suspension in water followed zero-order kinetics and the rate of degradation at room temperature was found to be 1.67 X 10(-7) mg/ml.s. An in vivo test by using 12 rabbits given BCTX suspension and CTX solution intramuscularly was conducted. The results showed that the former was longer in maintaining serum drug level than the latter. PMID- 2239323 TI - [The pharmacokinetics of dihydroqinghasu given orally to rabbits and dogs]. AB - Qinghaosu (QHS), also known as artemisinine and arteannuin, is isolated from the Chinese herb Artemisia annua L. It is highly active against both chloroquine sensitive and chloroquine-resistant strains of P. berghei and has been approved by the Ministry of Health for the treatment of malaria. When QHS is treated with sodium borohydride, dihydroqinghaosu (DH QHS) is resulted with the antimalarial activity enhanced several fold. This paper reports the pharmacokinetics of DHQHS studied with the radioimmunoassay method. When the drug was given orally in tablet form to rabbits at doses of 10, 20 and 30 mg/kg, peak serum levels of 0.03, 0.05 and 0.13 micrograms/ml, respectively, were obtained in 1 to 2 h. The corresponding T1/2 of the drug were found to be 1.19, 1.00 and 1.10 h and the MRTs were 1.73, 1.36 and 1.53 h. No significant difference between dosages used was observed. When dogs were given DHQHS tablets at the dose of 20 mg/kg, a peak serum concentration of 0.13 micrograms/ml wes reached in about 2 h with a T1/2 of 2.10 h and an MRT of 3.04 h. However, when dogs were given QHS tablets at the dose of 70 mg/kg, no drug was detected in the serum. It would appear that the bioavailability of DHQHS tablets is much higher than that of QHS when given orally to the dog. PMID- 2239325 TI - [Study on the determination of zinc in plasma after oral administration of licorzin by atomic absorption spectrophotometry and the pharmacokinetics of zinc in healthy volunteers]. AB - A rapid, accurate and sensitive atomic absorption spectrophotometry was established for the determination of zinc in plasma after oral administration of licorzin to healthy volunteers. The plasma sample diluted with de-ionized water (1:1) was determined directly. A 5% glycerol solution was used as the solvent of zinc standard solution. The recovery of the proposed method was 97.3 +/- 4.3%. The precisions (CV%) of within-day and day-to-day were less than 5%. The pharmacokinetics of zinc in healthy volunteers after oral administration of 2.5 g licorzin was studied. The results showed that an one-compartment model (Ka = K) was found in 10 healthy volunteers. The pharmacokinetic parameters were as follows: Ka = K = 0.380h-1, Tmax = 2.7h, V = 33.03 L, T1/2 = 1.9h. PMID- 2239324 TI - [A new diterpenoid quinone sapriparaquinone]. AB - A new diterpenoid quinone, named sapriparaquinone (1) was isolated from the root of Salvia prionitis Hance. 1 was identified as 3-hydroxy-6-methyl-2-(1-methyl)-5 (4-methylpenten-3-yl)-1, 4-naphthoquinone by spectral analysis and chemical transformation of saprorthquinone (2). 1 and 2 are 4,5-seco-5, 10-frideoabietane derivatives and must be biogenetically derived from an abietane structure. Like 2, 1 also showed cytotoxicity against P388 leukemia cells. PMID- 2239326 TI - [Use of fluorescence polarization immunoassay and microbiological assay in the study of gentamicin pharmacokinetics in man and a comparison of the results]. AB - Ninety serum samples of gentamicin were determined by fluorescence polarization immunoassay (FPIA) and microbiological assay (MA) and the results were compared. Liner regression analysis showed that the two methods were highly correlated with a correlation coefficient of 0.98. The mean concentration of gentamicin as determined by MA method was significantly higher than that by FPIA method. Serum concentration-time data derived from 5 patients were fitted to a one-compartment model. No significant differences in the pharmacokinetic parameters and estimated dosages were observed. The FPIA method was shown to be as correct and reliable as the MA method in estimating gentamicin pharmacokinetic parameters. PMID- 2239327 TI - [Studies on anti-implantation and hormone activity of yuehchukene, an alkaloid isolated from the root of Murraya paniculata]. AB - Oral or subcutaneous administration of yuehchukene to female mice at the dosage of 2 or 4 mg/kg.d on day 1-3 of gestation resulted in 100% anti-implantation effect. However, yuehchukene at 4 mg/kg.d was found to have no anti-implantation effect in hamsters. Allen-Doisy test showed that yuehchukene had obvious estrogenic activity. Treatment of immature mice with yuehchukene at the dosage of 2 or 4 mg/kg.d for 3 days caused an increase of uterine weight. Combined use of yuehchukene with estradiol was shown to have synergistic effect on promoting uterine growth. Experiments showed that the estrogenic activity of yuehchukene was weaker than that of estriol. The affinity of this compound for estrogen receptor was also found to be weaker than that of estriol. PMID- 2239328 TI - [Effect of scopolia drugs on the gastric mucosal lesion in rats]. AB - In the present paper, effects of scopolia drugs (scopolamine, anisodine, anisodamine) on experimental gastric mucosal lesion models in rats were investigated. Scopolia drugs were found to be effective anti-ulcer agents in three experimental gastric ulcer models (i.e. cold-restraint stress induced ulcer, indomethacin induced ulcer and acetic acid induced chronic ulcer) in rats in a dose dependent manner. Biochemical analysis of gastric juice and blood showed that scopolia drugs could inhibit gastric acid secretion and pepsin activity, increase gastric barrier mucus and concentration of serum gastrin, suggesting that these actions may contribute to its anti-ulcer effect. PMID- 2239329 TI - [Studies on biotransformation of jing song ling, a new anesthetic]. AB - Jing song ling (2,4-xylidinothiazoline, XT) is a new anesthetic agent for veterinary uses in China. From urine of rats given the drug three metabolites (MA1, MA2 and MB3) were isolated with structure shown in page 98 in addition to the parent compound (MB1). Preliminary observations showed that the toxicity and pharmacological activity of MB3, MA2 and MA1 decreased significantly compared with the parent drug XT. Species difference of biotransformation of XT between rat and mouse was also observed. PMID- 2239331 TI - [Synthesis of 2-methyl-5-substituted phenoxy-primaquine and antimalarials activity]. AB - In searching for efficient, safe and radically curative agent and causal prophylactics for malaria, seven 2-methyl-5-substituted phenoxy-6-methoxy-8-(1 methyl-4-aminobutylamino)-quinolines (II1-7) were synthesized and their antimalarial activities were compared with the corresponding 4-methyl substituted derivatives of primaquine. The starting material, 2-nitro-4-methoxy-5-bromo acetanilide (III), was prepared from p-methoxy aniline through acetylation, bromination and nitration. III was then condensed with substituted phenols in the presence of potassium carbonate. The condensed products were subsequently hydrolyzed with dilute alcoholic hydrochloric acid to yield 2-nitro-4-methoxy-5 substituted phenoxy-aniline (V) which underwent Skraup's reaction with 2-butenal to provide the key intermediates 2-methyl-5-substituted phenoxy-6-methoxy-8 nitroquinolines (VI). These 8-nitroquinoline derivatives were reduced to 8 aminoquinoline derivatives (VII). The latter were condensed with 4-bromo-1 phthalimido-pentane and then hydrolyzed with hydrazine hydrate, the final products were obtained as oxalate or succinate. The structure of the target compounds and unknown intermediates were confirmed by elementary and spectral analysis. Primary biological evaluation showed that all compounds II1-7 were much less active than the 4-methyl substituted derivatives and slightly less active than primaquine in both causal prophylactic test against Plasmodium yoelii and suppressive antimalarial test against P. berhei. PMID- 2239330 TI - [Effects of the polysaccharides isolated from mycelium and fermentation fluid of Schizophyllum commune on immune function in mice]. AB - SPG1 and SPG2 are polysaccharides extracted respectively from fermented cultural mycelium and fermentation fluid of Schizophyllum commune. This paper reports the effect of SPG1 and SPG2 on concanavalin A (Con A) induced proliferation of lymphocyte from C57BL/6J mice in vitro. SPG1 (10, 25, 50 and 100 micrograms/ml) and SPG2 (10, 50 and 100 micrograms/ml) was found to significantly increase lymphocyte proliferation. In addition, SPG1 (10, 25, 50 and 75 micrograms/ml) antagonized the suppressive effect of hydrocortisone on proliferation of mouse spleen cells, while SPG2 did not. In vivo, at the dose of 2.5 and 5.0 mg/kg ip for 9 days, SPG1 and SPG2 remarkably enhanced the delayed-type hypersensitivity to 2, 4-dinitrochlorobenzene (DNCB) in mice. SPG1 (1.25, 2.5 and 5.0 mg/kg, ip for 1 day) and SPG2 (2.5 and 5.0 mg/kg, ip for 1 day) promoted the plaque forming cell (PFC) response to sheep red blood cells (SRBC) in mice. The effects of SPG1 and SPG2 on immune function were studied in aged immunodeficient mice. SPG1 (10 and 25 micrograms/ml) and SPG2 (25 micrograms/ml) was found to enhance the Con A induced lymphocyte proliferation in 14 months aged mice. At the dose of 2.5 mg/kg, SPG1 and SPG2 produced respectively 162.1 and 136.0% increase in PFC response in 14 months aged mice. PMID- 2239332 TI - [Structure correction and synthesis of subspinosin]. AB - "Subspinosin" isolated from the root of Damnacanthus subspinosus Hand-Mazz (Rubiaceae) and deduced as 3-ethoxymethyl-2-hydroxy-1-methoxyan-thraquinone 1 by Li et al in 1981, should be corrected as 2-ethoxymethyl-3-hydroxy-1 methoxyanthraquinone 5 by comparison with the synthetic compound. Since 5 is already known as damnacanthol-omega-ethyl ether, the name "Subspinosin" for 1 (not yet a natural isolate) should be abandoned in order to acknowledge this priority, and, what is more, to avoid confusion. The anthraquinones 1 and 5 were synthesized by condensation of phthalic anhydride with 3-methylcatechol or 2 methylresorcinol in fused AlCl3/NaCl (5:1), followed sequentially by selective acetylation, methylation, bromination and condensation with sodium ethoxide. PMID- 2239333 TI - [Studies on the alkaloids of Gynura segetum (Lour.) Merr]. AB - Six alkaloids were isolated from Gynura segetum (Lour.) Merr. Four of them were identified. Alkaloids I and II were identified as known senecionine and seneciphylline, respectively. Alkaloids III and IV were found to be new compounds named seneciphyllinine and (E)-seneciphylline respectively. Their structures were confirmed on the basis of spectral data (UV, IR, MS, 1HNMR, 13CNMR, C-H COSY). PMID- 2239334 TI - [A rapid FIA-spectrophotometric method with online extraction for the content uniformity test of atropine sulfate tablets]. AB - A rapid spectrophotometric method based on FIA for the content uniformity test of atropine sulfate tablets has been developed. By means of the self-designed FIA system with an on-line extraction device, many difficulties resulting from extraction, such as slow analytical rate, environmental pollution, poor reproducibility, etc, were overcome, and the routine procedure of the official content uniformity test was tremendously simplified. Results obtained with the proposed method agree well with those obtained with the official test. Furthermore, the proposed method attained a sampling rate of 60 samples per hour, a recovery of 100.0%, a relative standard deviation of 0.7%, and a detection limit of 0.24 micrograms/ml. Uniform design proves effective to optimize complex FIA conditions, and FIA promises a new approach to test the content uniformity of pharmaceutical tablets. PMID- 2239335 TI - [Application of convolution curve method for simultaneous determination of four components in somidon]. AB - The computer-aided convolution curve method has been applied to the determination of phenacetin, aminopyrine, caffeine and phenobarbitone in the tablet of somidon without prior separation. The convolution curve method is a compound difference method developed on the basis of Glenn's orthogonal function using computer information treatment technique. The corresponding average recovery and the coefficients of variation were as follows: 99.96, 0.36% for phenacetin; 99.76, 0.43% for aminopyrine; 99.98, 0.48% for caffeine and 99.26, 0.89% for phenobarbitone. PMID- 2239336 TI - [Screening for in vitro metabolites of meisoindigo using RP-HPLC-DAD with gradient elution]. AB - A method of screening for in vitro metabolites of meisoindigo using RP-HPLC-DAD (photodiode array detector) with gradient elution was reported. Meisoindigo, a new structural antitumor agent, was metabolized by rat liver microsomes in vitro. The extract of the metabolic sample was dissolved in MeOH-acetone (9:1). An aliquot of the solution was injected onto a 5 microns YWG-C18 (ODS) column (15 cm X 4.0 mm I D) and separated with H2O (0.05% H3PO4)-MeOH in linear gradient elution. The flow rate was 0.5 ml/min and the oven temperature was 40 degrees C. Two simultaneous monitoring wavelengths (270 and 380 nm) were used in order to avoid detective losses of unknown metabolites. The spectral recording range of chromatographic peaks was set from 220 to 440 nm. After comparison of the chromatograms and the spectra of chromatographic peaks, ten metabolites were screened out which gave similar spectrum. Of them, the main chromatographic peaks (No. 7, 8) were confirmed as two monohydroxy metabolites by EI-MS. Their relative contents were calculated by area normalization method. The experimental results show that this method is characteristic of highly effective separation and specific detection. The whole analytical course can be completed in less than two hours. The effects of different elution models, detective parameters and components of mobile phase on the analytical results were discussed. PMID- 2239337 TI - [Bioavailability studies on the preparations of biphenyl dimethyl dicarboxylate(DDB)]. AB - Since the bioavailability of the suspension and the tablet of DDB given orally is only 20-30%, we have prepared four kinds of DDB solid dispersion preparations (DDB pilule I with polyethylene glycol 6000 as the vehicle, DDB pilule II with polyethylene glycol 6000 and absorption accelerator as the vehicle, capsule of DDB-urea fusing mixture and DDB-polyvinyl pyrrolidone coprecipitate), and the bioavailability of these preparations were studied in rabbits, rats and human volunteers by HPLC method. All four preparations showed better absorption than the DDB tablet, and the area under serum DDB concentration-time curve of pilule II was 19 fold that of the tablet in rabbits, meaning that the absorption of pilule II is the best of the four preparations. After administration of the four solid dispersion preparations, the fecal excretion of DDB were all lower than the tablet in both animals and human volunteers. The protective action of pilule II against CCl4 hepatotoxicity was about six times stronger than that of the suspensions. Therefore, there are good reasons to use DDB pilule II instead of the tablets of suspension in the clinic. PMID- 2239338 TI - [Effect of artesunate transdermal preparation on Plasmodium cynomolgi]. AB - Artensunate transdermal preparation at 5, 10, or 15 mg/kg, bid, for 3 days applied locally on the shaved skin of the back of monkeys showed reliable therapeutic effects on Plasmodium cynomolgi, but recrudescence of the parasites was not controlled. If some azone was added in the artesunate transdermal preparation at the dosage of 5 mg/kg, bid, for 3 days, the parasitemia of Plasmodium cynomolgi could be cleared and recrudescence prevented, thus, the antimalarial effects was enhanced. PMID- 2239339 TI - [Deformation phenomena occurring during compression. III. Changes of maximal compression strength in quasi-static condition]. AB - Four materials of different properties in respect of compressibility, lactose, sodium chloride, microcrystalline cellulose (Avicel PH 101) and so-called simple granulate were investigated. In function of time and that of actual pressing force decrease of axial force on upper punch were measured in quasi-state. Evaluating relations it was established that both pressing time and pressing force had influence on deformation structural changes occurring inside compressed form. Furthermore, summing up of results showed that useful conclusions could be drawn from diagrams--which represented decrease of force--to compressibility properties of materials too. PMID- 2239340 TI - [Electroanalysis of nifedipine]. AB - Nifedipine is an electrochemically active compound. Reducibility of 2-nitrophenyl group on dropping mercury electrode renders polarographic determination of nifedipine possible. Reductive half-wave potential of nitro group depends on saturation of neighbouring pyridine ring i.e. 1,4-dihydropyridine is reduced on more negative potential than aromatic pyridine derivatives. The different half wave potentials can be explained with the different stereo structures. On this basis differential pulse polarographic (DPP) method was developed for determination of nifedipine and its photolytic decomposition products (its aromatic nitro and aromatic nitroso derivatives). The DPP method has been suitable for determination of pharmaceutical preparations (tablets and capsules) as well as for pharmacokinetic determination of plasma levels. The fact that 1,4 dihydropyridine functional group is oxidizable has made possible selective voltammetric determination of nifedipine (on graphic and platinum electrodes) and its EC detection in liquid chromatography. Mechanism of oxidation was studied with comparison to analogous chloro derivatives. PMID- 2239341 TI - [Biopharmaceutical study of aminophenazone-containing suppositories. 1. Experimental materials and methods, determination of physical qualities of the suppositories]. AB - Suppositories containing aminophenazone in quantities of 0.30 g/2 g were prepared by pouring technology. Two kinds of lipophilic suppository masses Witepsol W 35 and Estarinum 299 have been used as vehicles. Both of suppository bases are official in Ph. Hg. VII. As ingredients ten sorts of liquid tensides in concentrations of 5% have been applied. Experimental methods have been described: compression stability, disintegration time, special penetration time and drug release of suppositories by membrane diffusion method. Results of determinations have been discussed in the second part of the publication. On the basis of experimental results it has been established that the physical parameters of Massa Estarinum 299 had proved to be more advantageous. In 5% concentrations tensides softened consistency of suppositories favorably and shortened disintegration time beneficially in the case of both vehicles. The authors think that special penetration time is more suitable for measuring "disintegration" of suppositories of high powder content at 37 degrees C than the classical disintegration time. PMID- 2239342 TI - [Biopharmaceutical study of aminophenazone-containing suppositories. 2. Results of in vitro drug release and in vivo drug absorption]. AB - Ten kinds of surface active ingredients of Th. Goldschmidt AG. (Essen-FRG) in concentrations of 5% were mixed with Witepsol W 35 and Massa Estarinum 299 suppository masses of Huls-Troisdorf AG. Werk (Witten-FRG) which are official in Hungary. According to the authors the above tensides, which have been used advantageously first of all in ointments, creams and cosmetic preparations, can also be applied in rectal preparations. In the publication of two parts it has been established that these ingredients influence physical parameters of suppositories beneficially. They always increase significantly in vitro diffusion values and in some cases with order of magnitude. Massa Estarinum 299 containing 5% of Emulgator BTO proved to be the best in case of chosen suppositories containing aminophenazone. Correlation between in vitro and in vivo investigations has shown the importance of correct selection of base and ingredient materials in biopharmaceutical work. PMID- 2239343 TI - [Determination of paracetamol in urine by liquid chromatography]. AB - Since the biotransformation of paracetamol (Acetaminophen) is practically confined to conjugation, the quantitative determination of paracetamol excretion may provide important information on phase II of the drug metabolism. We elaborated a simple and rapid liquid chromatographic method for the assessment of paracetamol and its conjugated metabolites in the urine to be available for routine use in the clinicopharmacological laboratory. The persons involved in the trial were administrated 500 mg of paracetamol to be taken on an empty stomach in the morning. Subsequently, their urine was collected for 8 hours. The so-called free paracetamol of unchanged form excreted into the urine was measured from this 0 to 8 hours' urine fraction, then, after treating it with beta glucuronidase/arysulphatase enzyme, the total amount of paracetamol released from the conjugate, as well as that of the existing free paracetamol, the so-called total paracetamol were determined. The urine extracts containing paracetamol obtained by ethylacetate, at pH 10, and dried under nitrogen stream were analysed by HPLC on an ODS column in an eluent of methanol and water mixture (3:7, v/v) in the presence of 3-acetaminophenol internal standard. The flow rate was 1 ml/min, the detection wavelength was 254 nm. PMID- 2239344 TI - [Bromatometric determination of oxprenolol]. AB - A bromatometric method was elaborated for the quantitative determination of oxprenolol. 15 to 150 mg of oxprenolol dissolved in 10 cm3 of water is brominated by adding 20.00-40.00 cm3 of 0.02 or 0.1 N potassium bromate solution followed by 0.5-3 g of potassium bromide and 1-10 cm3 of 10% w/w hydrochloric acid. After a reaction time of 15 min. 2-10 cm3 of 10% w/w potassium iodide solution is added followed by 20-40 cm3 of chloroform. The liberated iodine is titrated with standard 0.1 N or 0.01 N sodium thiosulphate solution. A blank titration is also performed and the oxprenolol content is calculated from the difference of the two titrations. Under these conditions one oxprenolol molecule reacts with six bromine atoms. The relative standard deviation is 1.31%. PMID- 2239345 TI - Exercise-induced muscle fatigue: the significance of potassium. PMID- 2239346 TI - Renal hypertension following aortic constriction is abolished by angiotensin II converting enzyme inhibitor, but not by low-salt diet. AB - This study evaluates the role of different sodium intakes and the role of angiotensin II in the development and the maintenance of renovascular hypertension in rats with constriction of the aorta proximal to the renal arteries. The rats were studied 3 weeks after surgery when the hypertension was well established. Glomerular filtration rate was decreased and filtration fraction was increased in rats with proximal aortic constriction. Low and high salt intakes had no effect on glomerular filtration and filtration fraction. Treatment with angiotensin II converting enzyme inhibitor increased the glomerular filtration rate and reduced the filtration fraction in rats with proximal aortic constriction to the same levels as in control rats. Serum levels of angiotensin II were about the same in rats with proximal aortic constriction as in control rats. Conclusion. The renovascular hypertension in proximal aortic constriction is influenced by locally formed angiotension II but not by alterations in salt intake. PMID- 2239347 TI - Plasma catecholamines, corticosterone, glucose and fatty acids concentrations and mean arterial pressure and body temperature in haemorrhagic hypovolaemia, hypothermia and a combination of these in the rabbit. AB - Venous plasma noradrenaline, adrenaline, dopamine, corticosterone, glucose and free fatty acid concentrations were measured in anaesthetized rabbits during hypovolaemia, hypothermia and a combination of these. The anaesthetic used was Hypnorm, which contains fentanyl and fluanisone. In the hypovolaemia group blood was shed via the venous cannula until the mean arterial pressure was 50 mmHg. The rabbits in the hypothermia group were cooled in iced water to a central temperature of 32 degrees C, and the rabbits in the combined hypovolaemia hypothermia group were bled until hypovolaemic and then cooled in iced water to a central temperature of 32 degrees C. Rewarming was done in dry air at 43 degrees C. Bleeding and hypothermia activated the sympathicoadrenal system, causing a rise in the noradrenaline and adrenaline concentrations, as well as a rise in corticosterone. There were no significant differences in plasma noradrenaline and adrenaline values between the groups, whereas hypovolaemia alone also increased the dopamine concentration. In the hypothermia group the amount of corticosterone after cooling and rewarming was higher than in the combined group. Hypothermia and hypovolaemia increased the level of free fatty acids and blood glucose, which in the hypovolaemia group remained higher after volume replacement than in the other groups. Hypothermia in both groups increased the mean arterial pressure. In conclusion, the results suggest that hypothermia may prevent some harmful effects of hypovolaemia, e.g. by correcting mean arterial pressure, thus preventing the mortality seen in the hypovolaemia group. PMID- 2239348 TI - Influence of the interval between removal and freezing of muscle samples on muscle fibre size with special reference to sample size and fibre type. AB - To study the influences of the interval between removal and freezing of a muscle sample on fibre size, rat hindlimb muscles (soleus and extensor digitorum longus, EDL) were cut into three or five pieces and frozen at different intervals, cross sectioned, stained and analysed morphometrically. As in a previous study (Larsson & Skogsberg 1988), a pronounced interval-dependent change in soleus muscle fibre size was observed, the fibres in soleus muscle samples frozen immediately (within 15 s) being significantly (P less than 0.01-0.001) larger than those samples frozen 4 or 10 min after removal. However, the interval-dependent change was only noted in small muscle samples, i.e. those where the maximum muscle fibre length was 6.5 mm, while samples in which the fibres were approximately twice this length showed no change. In the slow-twitch soleus, type I fibres predominate, and type II fibres were often too few in one or more cross-sections in each animal to allow reliable measurements of fibre size. The fast-twitch EDL was therefore studied, and the results indicated an interval-dependent change in fibre size which was differentiated according to enzyme-histochemical type, i.e. there was a significant change in type I and IIA fibres but not in type IIB. It is concluded that the interval between removal and freezing of small muscle samples, as in percutaneous muscle biopsies in man, is of vital importance for fibre size, and that this interval should be at least 2-4 min. PMID- 2239349 TI - ATP content in single fibres from human skeletal muscle after electrical stimulation and during recovery. AB - The ATP content was measured in type I and type II fibres from human vastus lateralis muscle at rest, after electrical stimulation and during recovery. At rest the mean values were 25.2 +/- 4.02 and 25.9 +/- 3.62 mmol kg-1 dry muscle (mean +/- SD) for type I and type II fibres respectively. Normal distribution curves were found for both types I and II fibres. After intermittent electrical stimulation for 83 s (1.6 s stimulation, 1.6 s pause) with occluded blood flow, the force generation decreased to 22% of the initial value and the muscle tissue showed a mean decrease in ATP to 14.8 and in phosphocreatine to 5.44 mmol kg-1 dry muscle; lactate increased to 128.9 mmol kg-1 dry muscle. The ATP content in isolated fibres was equally decreased in both fibre types to 16 mmol kg-1 dry muscle. In 11% of the fibres the ATP content was lower than 10 mmol kg-1 dry muscle. After 15 min rest with intact blood circulation ATP was completely resynthesized in type I fibres and to 91% in type II fibres. PMID- 2239350 TI - Influence of reduced glycogen level on glycogenolysis during short-term stimulation in man. AB - The relationship between muscle glycogen concentration and the rate of glycogen breakdown during short, intense contraction has been investigated in man. Prior to the experiment, muscle glycogen content was manipulated by a combination of exercise and diet, and varied from 155 +/- 19 to 350 +/- 25 mmol kg-1 dry muscle (36-81 mmol kg-1 wet wt). The quadriceps femoris muscle was stimulated electrically at a frequency of 20 Hz for 1 min. The blood flow to the leg was occluded during the experiment and muscle biopsies were taken before and after 10, 30 and 60 s stimulation. Force development and glycogenolytic rate were maintained constant during electrical stimulation and similar in all conditions, irrespective of the initial glycogen concentration. The phosphorylase a fraction was increased after 10 s stimulation, but returned to the initial values at the end of the stimulation. Muscle ATP was unaltered during the first 30 s stimulation, but decreased thereafter. The decrease in ATP was accompanied by a stoichiometric increase in inosine monophosphate. Phosphocreatine decreased during stimulation and was almost depleted at the end of stimulation. Muscle lactate and glucose 6-phosphate (Glu 6-P) increased during stimulation. None of these changes was significantly affected by the reduced glycogen contents. It is concluded that the rate of muscle glycogen breakdown is not affected by the initial glycogen level in the range of 155 +/- 19 to 350 +/- 25 mmol kg-1 dry muscle. PMID- 2239351 TI - Glycogen and lactate metabolism during low-intensity exercise in man. AB - The influence of high lactate concentration on glycogen metabolism in active type I and inactive type II fibres was investigated. High muscle lactate concentration (26.7 +/- 1.4 mmol kg-1 wet wt) was achieved by three bouts (2 min duration) of bicycle exercise at 112% Vo2 max. Exercise was continued at 40% Vo2 max for 1 h. Serial venous blood samples and biopsies from the vastus lateralis muscle were taken. Over the first 20 min of this low-intensity exercise muscle lactate concentration decreased by 22.9 +/- 0.7 mmol kg-1 wet wt, while glycogen remained unchanged in type I fibres and increased by 20 mmol kg-1 wet wt in type II fibres. During the next 40 min of low-intensity exercise lactate decreased by 1.6 +/- 1.2 mmol kg-1 wet wt, while glycogen concentration decreased by 21 +/- 7 mmol kg-1 wet wt in type I fibres but remained stable in type II fibres. In a second series of experiments, in which lactate was allowed to disappear before the light exercise was started, no changes in glycogen concentration were seen in type II fibres during the 1 h of 40% Vo2 max exercise, while a continuous reduction in glycogen of 28 +/- 8 mmol kg-1 wet wt was found in type I fibres. The results indicate that in the presence of high lactate levels muscle glycogen was resynthesized in inactive type II muscle fibres, while lactate was oxidized in preference to glycogen in type I fibres. PMID- 2239352 TI - Viscoelastic properties of the slowly adapting stretch receptor muscle of the crayfish. AB - The viscoelastic properties of the muscle associated with the slowly adapting stretch receptor organ of the crayfish (Astacus astacus) were studied by recording the tension response to various length changes. When steady-state length changes were applied to the muscle, the tension developed in a non-linear way, increasing slowly for small extensions and rapidly when extension increased. Muscle tension responses to ramp-and-hold extensions were characterized by a transient peak followed by a gradual decline in tension. At the onset of the ramp the tension increased rapidly, similar to the response seen in resting skeletal muscle. The relation between peak dynamic tension and extension was non-linear. In a log-log plot the relation was linear with a mean slope of 1.4. At small extensions (less than 5%) the slope seemed to be lower. The experimental results have been analysed in relation to a viscoelastic model consisting of a Voigt element in series with a non-linear spring. The model could describe both the static length-tension relation and the dynamic response, but different parameters for the springs had to be used for the two cases. When the measured tension response was transformed by an exponential function of the squared tension, in accord with recent findings on stretch-activated channels, a good agreement was obtained with the time course of the receptor currents. Adaptation is thus likely to be caused by both the mechanical properties of the receptor muscle and the characteristics of stretch-activated channels of the neuron. PMID- 2239353 TI - Phencyclidine activates rat A10 dopamine neurons but reduces burst activity and causes regularization of firing. PMID- 2239354 TI - A psychiatric study of suicide among urban Swedish women. AB - A total of 104 suicides among women were investigated by means of a modified psychological autopsy, including interviews with survivors and a review of somatic and psychiatric records. Diagnosis according to Research Diagnostic Criteria (RDC) showed that 35% were suffering from a major depressive disorder during their final month and another 24% were also depressed; 12% were substance abusers and 14% had adjustment disorders. Two thirds had attempted suicide and another 23% had communicated suicidality in other ways. Slightly more than half of the women had been psychiatric inpatients and another 19% had at some time been outpatients. Fifty-seven percent had been psychiatric inpatients or outpatients during the final year of life. An increasing number of life events occurred during the final 6 months. In most cases the depressed women had been treated ineffectively with antidepressant drugs. PMID- 2239355 TI - Patient interactions in four psychiatric wards. AB - This article describes the interactions between patients and between patients and staff in 4 psychiatric wards. Two of the wards are acute admission units and 2 are for long-stay chronic patients. The hospital is diagnostically streamed so that not only does the average length of stay vary between wards but so, for one ward, does the predominant diagnostic group. Patient interactions were analysed in terms of 5 major interactional categories: individual verbal, individual nonverbal, group verbal, group nonverbal and physical. The results show that, although there was little change in the overall level of verbal interaction as a function of chronicity, there were large shifts in patient-patient and staff patient interaction rates. Variations between the 4 wards on the 4 other interactional categories are explained in terms of the known diagnostic characteristics of the patients. PMID- 2239356 TI - The new revolving-door patients: results from a national cohort of first admissions. AB - A cohort of all first admissions to New Zealand psychiatric hospitals and psychiatric wards of general hospitals in 1980 and 1981 was followed up for 5 years. The cohort consisted of 3875 males and 3965 females aged from 15 to 64 years. Of these subjects, 59.4% had only one admission; 14.6% met our criteria for a revolving-door patient, as they had 4 or more admissions within the 5-year follow-up period. Based on first-admission information, patients who were younger and had a psychotic diagnosis had an increased likelihood of becoming a revolving door patient. Stepwise logistic regression showed that younger age and psychotic diagnosis independently and in interaction were associated with a high probability of becoming a revolving-door patient. Although patients with a first admission diagnosis of schizophrenia constitute a large group of the new revolving-door patients for both males and females, for women those with affective disorders and for men those with substance abuse comprise the largest proportion of the new revolving-door patients. This is because affective disorders in women and substance abuse in men are the most common diagnoses on first admission, rather than because the disorders themselves are associated with a high probability of the patients having multiple admissions. PMID- 2239357 TI - The prevalence of schizophrenia in three counties in Ireland. AB - This article reports a study of the prevalence of schizophrenia in 3 counties in Ireland based on case-register data and using a standardized diagnostic instrument--the Present State Examination. The estimate of prevalence varies depending on the criteria of schizophrenia employed. A middle-range estimate of 3.9 per 1000 population does not differ substantially from previous estimates of prevalence obtained elsewhere. Over 60% of all schizophrenic prevalence patients and over half of schizophrenic inpatients did not score as cases, suggesting that the continued hospitalization of symptomatically recovered cases has given rise to the mistaken impression that the prevalence of schizophrenia is unduly high in Ireland. The work reported here indicates substantial differences between the results of case ascertainment by hospital admission data compared with those arrived at by standardized interview diagnostic techniques. PMID- 2239358 TI - Reactive psychosis among elderly people. AB - Two cases of reactive psychosis occurring over the age of 65 are briefly reported. The role of organic impairment and evaluation of previous psychiatric illness in the diagnosis of reactive psychosis in elderly people is discussed. In addition, a brief review of the relevant Scandinavian literature is provided. PMID- 2239359 TI - Alcohol consumption in parents and offspring: a study of the family correlation structure in a general population. AB - Alcohol consumption was recorded for 2390 spouses and 498 children of age 18 or above living with their parents. The spouse correlation was 0.67, whereas parent offspring and sibling correlations were all close to 0.35. This family correlation structure implies an upper limit for heritability of 0.44. The design does not permit a separation of effect of cultural (environmental) and genetic transmission in families, but comparisons with previous heritability analyses suggest that heritability is in fact close to the upper limit, implying little or no cultural transmission. There were virtually no correlations between alcohol consumption and symptoms of anxiety and depression. Nor did consumption correlate substantially with symptoms in first-degree relatives. These results do not support hypotheses of common genetic nor even of common environmental determinants for alcohol consumption and mental disorders. PMID- 2239360 TI - Do children with autism have March birthdays? AB - One hundred people with autistic disorder (DSM-III-R) without a known cause who comprised a total population of children with autism were compared with "autistic like" children, Asperger syndrome and age-matched comparison children from the general population and were examined with regard to month of birth. There was an excess of March birth in the group of children with autism. The possible reasons for this finding are discussed. PMID- 2239361 TI - From community mental health services to specialized psychiatry: the effects of a change in policy on patient accessibility and care utilization. AB - In 1975, a community mental health (CMH) centre with most of its resources channelled to outpatient services was set up in a defined catchment area of 75,000 inhabitants near Stockholm. In 1981, the CMH centre was allocated 3 inpatient wards of its own. An outpatient unit to treat long-term psychotic patients was also built up from existing resources. Emergency cases were directed to the primary health care services or to the emergency department of a hospital. During the same period, the number of doctors in the area's primary health care services increased fourfold. The social, demographic and diagnostic composition of the patient population and its utilization of in- and outpatient care in connection with these organizational changes are described. The population of the cathment area increased by 12.5% and the patient population decreased by 40%. The decrease was particularly great among first-time visitors (-54%), patients from lower social groups (-53%) and those with crisis diagnosis (-71%). The number of patients with psychoses increased (+26%). Outpatient visits and hospital utilization increased by one third. The number of compulsory admissions increased by 20% (still being far below the mean number in Stockholm). The decrease in the patient population is attributed to the reduction in accessibility to the CMH centre at a time when primary care services in the area were undergoing a sizeable expansion. The increased care utilization is the result of an internal redistribution of resources in favour of resource-demanding, long-term psychotic patients. PMID- 2239362 TI - Development of case vignettes to assess the mental health training of primary care medical officers. AB - This article reports the development of case vignettes as a method of assessing the short-term in-service training of primary care medical officers in mental health care. A pool of 18 case vignettes representing common psychiatric problems and a standard response sheet were written first. This was mailed to 45 psychiatrists for their comments. Based on the comments received from 21 psychiatrists, 2 sets of questionnaires with 7 vignettes in each set were developed. When administered to a group of 32 medical officers, this method of assessment was found to be sensitive in detecting gain in knowledge and skills following training. Further, performance on case vignettes was found to correlate positively with clinical skills when actual cases were given for assessment. PMID- 2239363 TI - Factor study of the Hamilton Rating Scale for Depression and the Bech Melancholia Scale. AB - In this study, a sample (n = 234) of elderly people between the ages of 60 and 95 was evaluated. Items from the Hamilton Rating Scale for Depression and the Bech Rafaelsen Melancholia Scale were factorialized using the oblique rotation method oblimin. Three clinically significant factors were obtained, accounting for 41% of variance. The first was interpreted as a dimension of inhibition and melancholic depression; the second, insomnia; and the third, somatic and psychic anxiety. It is concluded that the set of items on both scales increases the capacity for evaluating melancholic aspects of depression. In the interpretation of factor analysis, the possible artifact represented by the repetition of similar items must be kept in mind. Despite the loss of simplicity oblique rotation implies, it is considered preferable to orthogonal rotation since it allows for a greater congruity with clinical situations. PMID- 2239364 TI - The experience of dysmenorrhea and its relationship to personality variables. AB - The aims of this study were: to relate women's subjective experience of primary dysmenorrhea to psychogenic needs assessed longitudinally at the age of 15 and at the age of 25 in a nonclinical sample; to compare the psychogenic needs of women with severe primary dysmenorrhea with those of other women who never have experienced dysmenorrhea; and to examine whether women with severe dysmenorrhea were less conventionally feminine than women who never have experienced dysmenorrhea. At 25 years, 42% of the women experienced dysmenorrhea and 15% experienced pain that limited their daily activity. Differences in psychogenic needs according to the Cesarec Marke Personality Schedule and in psychological masculinity and femininity according to the Attitude Interest Schedule were found in women with severe primary dysmenorrhea compared with women who never experienced dysmenorrhea. The results indicate that women with severe dysmenorrhea have less self-esteem at 15 years, but compensate for this at 25 years by being more achievement-oriented and aggressive than women who never experienced dysmenorrhea. Further, women with severe dysmenorrhea are more conventionally feminine than women who never have experienced dysmenorrhea. PMID- 2239365 TI - Osteoclasts isolated from membranous bone in children exhibit nuclear estrogen and progesterone receptors. AB - Osteoclasts were isolated from membranous bone from four children without metabolic bone disease who were undergoing craniotomy for either tumor or trauma. Both freshly isolated osteoclasts and those cultured for 4-7 days exhibited the following characteristics: production of tartrate-resistant acid phosphatase (9.5 14.8 units), contraction in response to application of 100 mg/ml of human calcitonin, and formation of resorption lacunae on devitalized bone wafers. Nuclear estrogen and progesterone receptors were demonstrated by immunohistochemical techniques and quantitated in two of the patients by radioimmunoassay (estrogen receptor RIA, 23.6 and 23.8 cpm/micrograms protein; progesterone receptor RIA, 36.7 and 74.2 cpm/micrograms protein). The demonstration of sex steroid hormone receptors in the nucleus of osteoclasts derived from children with normal membranous bone has established a potential mechanism whereby direct modulation of bone resorption by the sex steroid estrogen and progesterone may occur. PMID- 2239366 TI - Chemotactic response of osteoblastlike cells to transforming growth factor beta. AB - Transforming growth factor beta (TGF-beta) has multiple effects on bone cell metabolism in vitro but its exact role in bone remodeling still needs to be defined. Here we demonstrate that TGF-beta is chemotactic for osteoblastlike cells from fetal rat calvariae and osteoblastlike ROS 17/2.8 osteosarcoma cells. Maximal chemotaxis occurred at 5-15 pg/ml of TGF-beta and was observed with TGF beta 1 and TGF-beta 2 at equivalent concentrations. Conditioned medium from osteoblastlike cells containing latent TGF-beta failed to stimulate chemotactic migration. However, chemotactic activity was observed in conditioned medium that had been transiently acidified. Since acidification is known to activate TGF beta, these results suggest that only active TGF-beta is capable of inducing a chemotactic response. Preincubation of osteoblastlike cells with TGF-beta in concentrations from 10 pg/ml to 1 ng/ml for 48 h abolished a subsequent chemotactic response of these cells to TGF-beta, indicating that TGF-beta-induced chemotaxis is a transient phenomenon. Since TGF-beta may be released from the bone matrix and/or activated during bone resorption, the chemotactic activity of TGF-beta for osteoblastlike cells may be important for the recruitment of osteoblastlike cells to sites of bone remodeling. PMID- 2239367 TI - Different pattern of alkaline phosphatase, osteopontin, and osteocalcin expression in developing rat bone visualized by in situ hybridization. AB - Alkaline phosphatase (AP), osteopontin (OP), and osteocalcin (OC) are expressed during osteoblastic differentiation. However, previous studies suggested differences in the timing and possibly the site of their expression. In this study we used in situ hybridization to follow the distribution of these osteoblastic markers during bone development. Frozen sections of neonatal rat long bones and calvariae were hybridized with 35S-labeled RNA probes complementary to the AP, OP, and OC mRNAs. Controls included sections hybridized with the sense (mRNA) probes or pretreated with RNase. Positive cells were identified in all areas of bone formation of the long bones and calvariae. Based on quantitative silver grain distribution and density, high levels of OP expression were present only in osteoblasts in close proximity to bone (one to two cell layers). OC expression, apparently at lower levels than OP, was also localized to osteoblasts in contact with bone. In contrast AP, which was expressed at lower levels than OP, was present in a large number of cells, including preosteoblasts that were many layers removed from the bone-forming surface. These findings are consistent with the asynchronous expression of phenotypically related genes and suggest that AP is an earlier differentiation marker than OP and OC during the formation of endochondral and membranous bone. PMID- 2239369 TI - T lymphocyte surface antigen markers in osteoporosis. AB - Two distinct syndromes of osteoporosis have been postulated: type I, which is characterized by accelerated bone loss occurring in women during the early postmenopausal period; and type II, an age-related process of bone loss affecting both men and women in and after the seventh decade. Recently there has been indirect evidence linking local products of the immune system with bone remodeling. We therefore studied peripheral blood profiles of specific lymphocyte phenotypes in women with type I osteoporosis and in older women and men with type II osteoporosis. The ratio of CD4-bearing (T helper) cells to CD8-bearing (T cytotoxic-suppressor) cells (CD4/CD8 ratio) was elevated in women with symptomatic type I disease. In addition there was a significant negative correlation (r = -0.62, P less than 0.001) between the CD4/CD8 ratio and the spinal bone mineral density measured by dual-photon absorptiometry. In contrast, older men with a history of fracture (hip or spine) had CD4/CD8 ratios similar to control men. The number of T cells bearing IL-2R or VLA-1 was not different between osteoporotic subjects and controls in either men or women. This study supports the concept that local products of the immune system may be directly or indirectly involved in the pathogenesis of type I osteoporosis. PMID- 2239368 TI - Bone mineral loss and recovery after 17 weeks of bed rest. AB - The purpose of this work was to determine the rate and extent of bone loss and recovery from long-term disuse and in particular from disuse after exposure to weightlessness. For this purpose, bed rest is used to simulate the reduced stress and strain on the skeleton. This study reports on the bone loss and recovery after 17 weeks of continuous bed rest and 6 months of reambulation in six normal male volunteers. Bone regions measured were the lumbar spine, hip, tibia, forearm, calcaneus, total body, and segmental regions from the total-body scan. The total body, lumbar spine, femoral neck, trochanter, tibia, and calcaneus demonstrated significant loss, p less than 0.05. Expressed as the percentage change from baseline, these were 1.4, 3.9, 3.6, 4.6, 2.2, and 10.4, respectively. Although several areas showed positive slopes during reambulation, only the calcaneus was significant (p less than 0.05), with nearly 100% recovery. Segmental analysis of the total-body scans showed significant loss (p less than 0.05) in the lumbar spine, total spine, pelvis, trunk, and legs. During reambulation, the majority of the regions demonstrated positive slopes, although only the pelvis and trunk were significant (p less than 0.05). Potential redistribution of bone mineral was observed: during bed rest the bone mineral increased in the skull of all subjects. The change in total BMD and calcium from calcium balance were significantly (p less than 0.05) correlated, R = 0.88. PMID- 2239370 TI - Fluoride bioavailability from slow-release sodium fluoride given with calcium citrate. AB - Clinical pharmacology of slow-release sodium fluoride given with calcium citrate was examined in acute and long-term studies. Following a single oral administration of 50 mg slow-release sodium fluoride, a peak serum fluoride concentration (Cmax) of 184 ng/ml was reached in 2 h; thereafter, serum fluoride concentration declined with a T1/2 of 5.9 h. The concurrent administration of calcium citrate (400 mg calcium) gave an equivalent Tmax (time required to attain Cmax) and T1/2, but a lower Cmax of 135 ng/ml. The coadministration of a meal with fluoride also reduced Cmax but increased Tmax. The area under the serum concentration curve of slow-release sodium fluoride was reduced 17-27% by a meal or calcium citrate. Thus, calcium citrate reduced fluoride absorption and peak fluoride concentration in serum of slow-release sodium fluoride but did not affect the time required to reach peak concentration or the rate of subsequent decline. The effect of a meal was similar, except for a longer period required to reach peak serum concentration. During long-term administration of 25 mg slow release sodium fluoride coadministered with 400 mg calcium as calcium citrate on a twice daily schedule, the trough level of serum fluoride could be kept between 95 and 190 ng/ml, believed to be the therapeutic window. PMID- 2239371 TI - Osteoporosis as the sole presentation of bone marrow mastocytosis. AB - Three (young) adults with severe generalized osteopenia and vertebral compression fractures were studied. Extensive clinical and laboratory investigations were not contributory. Undecalcified bone biopsies demonstrated multiple mast cell granulomas in the marrow in two patients and numerous mast cells diffusely distributed throughout the bone marrow in the third patient. Mast cells may serve as a pathogenic agent in osteoporosis. Therefore, we conclude that isolated skeletal mastocytosis without clinical evidence of mast cell mediator release should be sought in the evaluation of a patient with unexplained severe bone loss. PMID- 2239373 TI - L'art et la maniere. A French title for a European lecture. PMID- 2239372 TI - Effect of sodium warfarin on vitamin K-dependent proteins and skeletal development in the rat fetus. AB - Sodium warfarin was administered daily to Sprague-Dawley rats from gestational day 8 to day 22 to examine the effects of this compound on the developing fetal skeleton and on the vitamin K-dependent bone and cartilage proteins. At a dose of 175 micrograms/kg of sodium warfarin there was a 43% mortality rate among the dams. Maternal prothrombin times and serum osteocalcin levels were slightly elevated but not significantly. In the surviving litters, fetal bone osteocalcin and gamma-carboxyglutamic acid were significantly reduced (50 and 57%, respectively, on gestational day 22) when compared to age- and/or weight-matched control pups. The high correlation of osteocalcin content in long bone (R = 0.64) and calvariae (R = 0.77) to fetal body weight observed in control fetuses was not seen in the warfarin-exposed pups. Examination of alizarin-stained warfarin exposed fetal skeletons for ossification centers showed no difference from controls. However, analysis of the tibial growth showed several changes compared to control that included (1) widened hypertrophic zones, (2) increased calcification of the hypertrophic zones, and (3) disorganization of the hypertrophic cells. These results suggest that the growth plate abnormalities seen with prenatal warfarin exposure relate to the inhibition of the vitamin K dependent proteins of the skeletal system. PMID- 2239374 TI - Surgical management of brain stem vascular malformations. AB - Vascular malformations of the brain stem are a histologically heterogenous collection of lesions which most often present with sudden and progressive neurologic deficit related to haemorrhage. Since 1987 the authors have treated eleven cases of brain stem vascular malformation. Seven of the patients were treated with complete surgical extirpation of the haematoma and malformation because of progressive neurologic deficit. Four additional patients made a full neurologic recovery and are being carefully observed for signs suggestive of the need for surgical treatment. Complete surgical excision of brain stem vascular malformations is mandatory for patients with progressive neurologic deficit related to recurrent haemorrhage. PMID- 2239376 TI - Cerebral blood flow in moyamoya disease. Part 1: Correlation with age and regional distribution. AB - A study has been made of the cerebral blood flow (CBF) in moyamoya disease from the perspective of hemispheric cerebral blood flow and regional CBF (rCBF). The material includes 21 children between the ages of 5 and 15 years with moyamoya disease, and 19 adult moyamoya cases--all of which had virtually no neurological symptoms at the time of the study. CBF was measured using the 133Xe intravenous injection method. Comparison was made with the measurements from 16 normal children and 14 normal adults. Study was also made of the relationship between the angiographic stage of the disease and the CBF. With the exception of the more elderly patients, CBF was found to be significantly lower in the moyamoya cases than in normal subjects of the same age group. In all age groups, the distribution of rCBF showed a dominant posterior distribution, dissimilar to the dominant anterior distribution found in the normals. Among the juvenile moyamoya cases, there was a tendency toward decreasing hemispheric blood flow together with advancing disease--as determined angiographically. Moreover, with advancing stages of the disease, there was a continuing transition from the normal pattern of frontal dominance to one of occipital dominance. This dominance of posterior rCBF is thought to be a characteristic feature of moyamoya disease. PMID- 2239375 TI - Contrecoup fractures of the anterior cranial fossae as a consequence of blunt force caused by a fall. AB - Contrecoup fractures of the base of the skull are regarded as rare in the clinical literature. In our material (n = 171 falls on the same level and on or from stairs), the overall frequency of contrecoup fractures of the anterior cranial fossa in fatal cranio-cerebral trauma due to falls was 12%, as compared to 24% with occipital point of impact of the head. The relationships between the impact site on the head, form of fracture at the point of impact with involvement of the skull cap and/or the base of the skull, coup and contrecoup injuries of the brain, localization of contrecoup fractures in the anterior cranial fossa and the occurrence of monocle and spectacle haematomas display a major variability. Fractures occur in the form of simple fractures and as impression fractures (fracture fragments or fracture boundaries displaced to the inside). Clinical diagnosis is difficult because of the concealed position of the anterior skull base. Contrecoup fractures become of forensic medical significance when symptoms of a frontobasal injury occur for the first time after trauma which has occurred some time in the past and when the question arises as to the causal connection with the original trauma. In investigation of living persons, it may be difficult to decide whether haemorrhages in the region of the orbit and its vicinity result from a direct blunt force or derive from fractures of the base of the skull, especially contrecoup fractures. PMID- 2239377 TI - Histological differences between rootlets sectioned during selective posterior rhizotomy by two surgical techniques. AB - During selective posterior rhizotomy, for the treatment of spasticity in infantile cerebral palsy, the rootlets to be divided are chosen by the type of electromyographic response elicited by intraoperative electrical stimulation. Two different surgical techniques were used for exposing the lumbar roots. The first approach was to expose the conus medullaris through a T 12-L 1 laminectomy, while the other approach to the dorsal roots was distally in the cauda equina through a L 2-L 3 to S1 laminectomy. Although the clinical results obtained with either of them are not very different, there is anatomical evidence that suggests that the histological structure of the divided rootlets may be different in the two techniques. We designed our study to determine of a significant difference in the number of large myelinated fibers was found between rootlets divided close to the conus medullaris and those divided distally in the cauda equina. Two groups of five children with spasticity secondary to cerebral palsy where randomly designed to be operated upon by one of the techniques. The divided rootlets were processed with standard histological techniques and the large myelinated fibers were counted on enlarged (40 x) photomicrograph of the rootlet. A significantly (p less than 0.001) larger number of large myelinated axons was found in the rootlets dissected and divided close to the conus medullaris. PMID- 2239378 TI - Study of nerve regeneration in centrocentral anastomosis. AB - Nerve regeneration was studied in a model of centrocentral anastomosis (CCA) performed on the sciatic nerve of the rat. Experimental CCA was made by suturing the proximal end of the peroneal branch on the proximal end of the sural branch, placing between them a peroneal nerve graft (Group I, 20 rats) or a silicone chamber (Group II, 12 rats). Nerve grafts had a length of 5 mm and silicone chambers 7 mm. In six silicone chambers an 1 mm nerve graft was placed in the centre of the tube. In group I animals anterograde degeneration was studied by cutting the graft 60 days after surgery. In group II, nerve regeneration was studied 2, 4 and 8 weeks after surgery. Results indicate that in CCA: 1) regenerated axons coming from one nerve end grow into the graft but do not cross the contralateral suture line; 2) regeneration is poorer in silicone chambers than in nerve grafts; and 3) in silicone chambers regeneration is related to time. The reduction in the regenerative capability in CCA seems to be related to the alteration of nerve sprouts aiming for the peripheral targets. PMID- 2239379 TI - Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum). Report of a case and review of the literature. AB - The authors report the third published case of a Lhermitte-Duclos disease diagnosed preoperatively with the help of MRI, stressing its possible extension beyond the limits of the posterior fossa. The pertinent literature is reviewed concerning the clinical and radiological picture of this disease, as well as the different pathogenic hypothesis. PMID- 2239380 TI - Practical application of intraoperative ultrasound imaging. AB - Intraoperative real-time ultrasound imaging (US) was used in over 500 patients to investigate which of the previously considered applications are of practical use in everyday neurosurgery. During all intraoperative applications for a wide variety of pathological conditions, small deep-seated as well as subcortically located lesions were detected with accuracy; in many instances they could be approached through smaller surgical exposures. US guidance was accurate in 209 cases for the stereotactic introduction of needles or endoscopes into various lesions: thus burrhole evacuation was performed on 148 intracerebral haematomas; in 16 patients endoscopic biopsy and resection of ventricular tumours was performed as well as biopsies of 39 hemispheric brain tumours and aspiration of a brain abscess in 6 instances. Seventy six gliomas were investigated by US imaging; the frequently unclear boundary between tumour and surrounding oedema was not better visualized than with CT or MRI. Moreover, US imaging for the detection of residual tumour towards the end of operation was unreliable. Postoperative imaging through burrholes or other cranial defects was mostly of unacceptably low quality for therapeutic decision making. PMID- 2239381 TI - Metastatic adenocarcinoma in cerebral astrocytoma: clinicopathological and immunohistochemical study with review of the literature. AB - Metastatic spreading of carcinoma into a pre-existing cerebral glioma is extremely rare and only a few well-documented cases have been reported in the literature. Here we report a 53-year-old man who at the age 49 was first operated on for a frontal astrocytoma (WHO-grade II). This tumour was completely resected and no post-operative radio- or chemotherapy was applied. About five years later the patient presented again with a large partially cystic space-occupying lesion at the same site, which pre-operatively appeared as a recurrence of the astrocytoma. Histologically, however, this tumour proved to be a metastatic adenocarcinoma into a recurrent astrocytoma. Further clinical examinations revealed a bronchial carcinoma as the primary lesion responsible for this unusual metastatis. The clinical and neuropathological findings of this interesting case including immunohistochemistry are presented and discussed. PMID- 2239382 TI - Philosophical and ethical problems regarding life and death. PMID- 2239383 TI - Concepts of consciousness. PMID- 2239384 TI - The Abhidhamma view of consciousness. PMID- 2239385 TI - The Buddhist world-view and the scientific world-view: a comparative analysis. PMID- 2239386 TI - Regulations on brain death in the Netherlands. PMID- 2239387 TI - Evolution of criteria for determination of brain death in Japan. PMID- 2239388 TI - New law in Hungary, concerning brain death and organ transplantation. PMID- 2239389 TI - Brain death. PMID- 2239390 TI - [A 10-month experience with extracorporeal shockwave therapy of urolithiasis]. AB - From November 1987 treatment of urinary lithiasis regardless location was initiated in our Service of extracorporal renal lithofragmentation using shockwaves. Up until August 1988 (10 months), 411 patients have been treated representing a total of 590 lithiasis and 699 sessions on which the present communication is based; treatment included calculus of various chemical composition, as well as different sizes and locations. Also the relationship between sex, age, number of waves, use of analgesia, hospital stay, etc, has been considered. Results obtained after a 2.5 months follow-up are: 60.34% fragments free and 39.41% in expulsion stage. Monotherapy was chosen in 98% cases and multiple drug therapy in the remaining 2%. There has been no case of complementary open surgical therapy. Thus, we consider extracorporal renal lithofragmentation as the ideal treatment for urinary lithiasis, as long as the indication is correct. And we believe it to be the ideal treatment since it is a simple procedure, highly effective and with few complications. PMID- 2239391 TI - [Kidney transplantation]. AB - In a consecutive series of 639 Renal Transplants (RT) performed between January 1st 1978 and December 31st 1988, 75 Renal Transplanctectomies (RTX) were carried out. Of those, fifty-seven (76%) were due to immunological causes, 10 (13.3%) to vascular complications, 7 (9.3%) to urological problems and 1 (1.3%) to deep infection. The time elapsed between RTX and RT was as follows: 25 were performed earlier than 6 weeks, 17 between 6 weeks to 6 months, and 33 after 6 months. The higher number of complications did not happened, as it is frequently described, in the first group; on the contrary, it fell in the group that had been transplanted longer. There were 13 immunologically caused renal rhexis, 5 of which were RTX, another 5 were operated on and diagnosed at perioperation, and immediately received the appropriate treatment so they were able to keep their kidney, and finally, 3 patients were diagnosed a rejection with renal rhexis, ecographically confirmed. These patients were given only medical treatment, which was enough to allow jugulation of the picture. RTX techniques used were: extracapsular in 28 cases and intracapsular in 47. Surgical approach, except for 2 cases of simultaneous kidney and pancreas transplantation, was extraperitoneal. PMID- 2239392 TI - [Evaluation of the penile artery by ECO-Duplex in the diagnosis of erectile dysfunction]. AB - An Eco-Duplex study of the penile arterial system in 19 patients which consulted their physician for impotence is presented and a two-group classification is made: Group 1, arterial cause (7 patients) and, Group 2, non-arterial cause (12 patients). Diameter and blood flow of the cavernous artery pre-and post intracavernous injection of papaverine was evaluated. A significant difference was found in the increase of arterial diameter in both groups as well as in the quantification of arterial flow pre- and post-application of papaverine, these being larger than 32 cm/sec in all non-arterial impotent patients (group 2). PMID- 2239393 TI - [Limitations of CAT scan in the diagnosis of myelolipoma of the adrenal gland]. AB - The suprarenal myelolipoma is a myeloid tissue and fat tissue tumor. It can undergo degenerative processes of haemorrhage, necrosis and calcification. The diagnostic key is based on the finding of fat tissue in the inside of a suprarenal mass. A CAT would be the method allowing a more accurate diagnosis. Its limitations came from the presence of myelolipomas with abundant myeloid tissue, or which have suffered major degenerative processes in which it is difficult to identify the fat tissue, and in large retroperitoneal masses in which it is impossible to recognize their suprarenal origin. PMID- 2239394 TI - [Hypercalciuria and hyperuricosuria causing hematuria in the absence of nephrolithiasis]. AB - A prospective study was made of 38 adult patients (15 male and 23 female, age 30.5 +/- 10.8 years) with isolated hematuria of unknown etiology in which presence of hypercalciuria and/or hyperuricosuria without lithiasis was observed. Eighteen patients also referred episodes of macroscopic hematuria. Twenty-six patients had hypercalciuria (5.1 +/- 1.4 mg/kg/day), 29 hyperuricosuria (1053 +/- 198 mg/day) and 17 presented both alterations. A four months treatment was instituted with thiazides in patients with hypercalciuria and allopurinol in those with hyperuricosuria. From the first months and throughout the whole therapy, urinary excretion of calcium an uric acid became normalized in all cases. In 22 patients (57.8%) (Group I: Respondents) hematuria disappeared coinciding with normalization of calcium and uric acid values in urine and was maintained during the follow-up months. In the remaining 16 patients (Group II: Non-Respondents) the hematuria condition persisted in spite of such normalization, in most cases other causes for hematuria becoming clear later. No differences with regard to age, relationship male/female nor basal calciuria and uricosuria values were seen between both Groups. Group I had a greater incidence of macroscopic hematuria episodes (64% vs 12% in Group II, p less than 0.01) and of family nephrolithiasis (64 vs 25% in Group II, p less than 0.05). We conclude that hypercalciuria and hyperuticosuria are potentially reversible causes of hematuria in adults. Therefore, urinary determination of calcium and uric acid should be included in urinary evaluation of patients with hematuria even though they do not present renal lithiasis. PMID- 2239396 TI - [Use of an urologic resector in rectal pathology: experience at our office]. PMID- 2239395 TI - [In situ tumor excision of a renal neoplasm]. AB - The present work reviews the conservative surgical options to treat renal tumor formation in patients who still have both kidneys, and tries to clarify the diagnostic aspects, indications and therapeutical alternatives. The controversial items are analyzed versus treatments advocating a radical surgical approach, establishing a parallelism with current trends of surgical non-intervention in renal traumatism of moderate to severe condition (grade II). A case is presented where these two pathological circumstances are concurrent: Renal traumatism with complete parenchymatous rexhis and contralateral solid renal mass, both treated conservatively. Pre-surgical diagnosis was left renal traumatism grade II and righ renal neoformation and was based in findings with CAT and arteriographia. Histology of the piece from tumorectomy was renal angiomyolipoma. After a post surgical evolution of twelve months, therapeutical results were assessed as excellent, with no evidence of either immediate not late complications. Considering data recently communicated by most authors, the concept of simple tumorectomy or renal tumoral enucleation is suggested as valid. However, arguments both clinical and surgical, in order to confirm its indication, require very rigorous criteria and a careful selection of patients. PMID- 2239397 TI - [Paratesticular liposarcoma of the spermatic cord]. AB - Funiculus liposarcoma is a very uncommon tumor. Most cases have a low degree of malignancy. Inguinal orchiectomy with a wide local excision is the appropriate treatment. Liposarcoma presurgical diagnosis is very infrequent and ultrasonography is the method that can provide some help to locate it. Currently, chemotherapy indication is unclear. Due to recurrence, specially of local foci, being a possibility a periodical follow-up is necessary in these patients. Nowadays, local recurrences are treated with repeated ample local excisions and radiotherapy. This work reviews the literature and presents a new case of round cells liposarcoma of the funiculus. PMID- 2239398 TI - [Renal carcinoma and acquired cystic disease of the kidney in a patient after transplantation and under hemodialysis]. AB - Renal Acquired Cystic Disease (RACD) is a frequent entity in patients with a long standing renal failure under hemodialysis treatment. Incidence of a tumor pathology is higher in those patients than in the general population. A new case is presented and some possible etiopathologenical factors of RACD and neoplasias on such pathology are established. PMID- 2239399 TI - [The value of high dose steroid therapy in obstructive uropathy caused by a tumor]. AB - The case of an 82-years old female patient with acute renal failure secondary to tumoral obstructive uropathy by neoplasic invasion of the trigone is described. The condition was treated with urinary deviation through percutaneous nephrostomy of the left kidney which achieved an improvement in the renal function. Later, the percutaneous nephrostomy was unintentionally moved not being possible to place a new one in none of the kidneys. The patient remained anuric for 24 hours, and therapy was then instaured with high doses of intravenous steroids (6 Metyl Prednisolone 1.5 g I.V. in 24 hours), diuresis was recovered and renal function became normalized within a few days. The mechanism of action and therapeutic usefulness of high dosage steroids in tumoral obstructive pathology is discussed. PMID- 2239400 TI - [Cysts of the seminal vesicles. Diagnosis and treatment]. AB - Congenital cysts in the seminal vesicle represent a rare by illustrative example of embryological malformation. They are often associated with ipsilateral urinary tract anomalies. We have analyzed the diagnostic and therapeutic schemes followed in the study of this uncommon pathology. PMID- 2239401 TI - [Renal carcinoma associated with benign tumoral pathology of the adrenal glands]. AB - Three cases of renal carcinoma where homolateral suprarenal mass was detected during nephrectomy which was all together extirpated with the nephrectomy piece are presented. In all three cases pathological anatomy revealed a being suprarenal pathology (adenoma, myelolipoma, and cortical hyperplasia respectively). The infrequency of these pathologies association is commented upon and diagnostic methods to be used in its detection are discussed. PMID- 2239402 TI - [Late adrenal gland metastasis of contralateral renal adenocarcinoma]. AB - A case of adrenal gland metastasis caused by contralateral adenocarcinoma of kidney nephrectomized 11 years previously in a 68 years old patient is presented. The rarity of the case due to its limited frequency and the long disease-free interval is emphasized, and the possible routes of metastatic affectation of the adrenal gland by renal tumors discussed. PMID- 2239403 TI - [Renal hydatid cyst: a nuclear magnetic resonance study]. AB - A case of renal hydatid cyst (R.H.C.) in which study both traditional diagnostic methods (such as serology, radiology, ecoraphia, C.A.T., etc.) and the newer ones, including Nuclear Magnetic Resonance (N.M.R.) were used, is presented. The diagnostic characteristics of this type of cystic pathology were reviewed through N.M.R. study, as well as current criteria to outline a correct differential diagnosis with simple Renal Cysts (R.C.). Finally, a theoretical place for each of these methods within the diagnostic algorithm of renal masses is suggested. PMID- 2239404 TI - [Incidental carcinoma of the kidney with renal vein thrombosis]. AB - Incidental carcinoma of kidney is an increasingly common pathology as a result of a wider use of high resolution diagnostic methods. The special characteristics of these tumors, usually small and in a low grade or stage, make conservative surgery to be considered as a valid therapeutical option. An incidental carcinoma of kidney with tumoral thrombosis of the renal vein undetected in the pre surgical study, circumstance which allows to emphasize the malignant potential of these tumors is presented here. Based on this, we believe that a meticulous evaluation of the renal vein condition should be made, in patients considered as possible candidates for conservative surgery. In this sense, selective renal phebography and magnetic resonance could be considered explorative means that play an important role in the introduction of renal preservation surgery, if future studies show that its use allows an early detection of the tumoral condition of renal vein. PMID- 2239405 TI - [Testicular malacoplakia]. AB - This paper present the case of a patient with orchioepidimiditis quickly evolving to scrotal fistulization. The study of the orchiectomy piece showed testicle malacoplakia. PMID- 2239406 TI - [Thyroid metastasis of renal carcinoma]. AB - Clinical detection of thyroideal metastasis of renal carcinoma is very rare; diagnosis of this type of metastasis is usually done at post-mortem examination. A case of thyroideal metastasis six years after nephrectomy due to renal carcinoma is presented. The slow evolution and good prognosis following surgical exercises justify an active therapy. Thirty-two months after the operation our patient is still free from the disease. PMID- 2239407 TI - [Growing teratoma syndrome in metastatic germinal non-seminomatous testicular tumors]. AB - Presence of retroperitoneal or mediastinal mature teratomas secondary to metastatic testicle germinal tumours which have not responded to multiple chemotherapy constitute the so called Growing Teratoma. They can either represent the metastasis of a mature teratoma site in the original testicle tumour or the evolution from a non-differentiated lesion during therapy. The first two cases of Growing Teratoma Syndrome published in the national literature are presented here. Both cases had a retroperitoneal growth of the mature teratoma following successful achievement of normalization of serum tumoral markers through chemotherapy with CDDP, Bleomycin, and VP-16 in one case (Hospital Clinico) and with BOMP/EPI (Belomycin, Metrothexate, Vincristine, Cisplatin/Vo-16, Cisplatin, Iphosphamide) in the second one (Hospital del Mar) of a non-seminomatose testicle tumour. After a follow-up of 14 and 9 months respectively the good prognosis of these mature teratomas was verified in both cases, so as in the rest of the literature. We coincide with regard to performing a retroperitoneal lymphadenectomy with exeresis of tumoral masses as the most adequate attitude, both to prevent growth of the mature teratoma and to allow us to discard the presence of residual immature lesions. PMID- 2239409 TI - [Bonding and enamel prisms: is the "bevel" still significant?]. AB - Following a recall of the various preparations of the cavo-surface for posterior composites (straight, rounded, concave bevel, or without bevel), a study at the M.E.B. analysed the interface between the tooth and the filling in each case investigated. With the straight bevel with a slight angulation (40 degrees), the limit of the cavity-filling joint is clear. A disintegration of the material exists with the straight bevel having a 70 degrees angulation. The hiatus is even more marked with rounded or concave bevels. The absence of a bevel provides a clear occlusal joint without irregularity at the cavo-surface limit. In the light of this investigation and the results observed in the clinic in the medium and long term, it appears that the preparation of the cavo-surface margins of occlusal cavities of the pre-molars and molars for posterior composites may make do with a bevel which is not very extensive and not widely opened (40 degrees), or even the total absence of a bevel. PMID- 2239408 TI - [Left supraclavicular adenopathy as a symptom of prostatic adenocarcinoma]. PMID- 2239410 TI - [Influence of chemical composition and polymerization technic on the quality of removable denture resins]. AB - With the new means of investigation, such as scan electron microscopy and gaseous phase chromatography combined with mass spectrometry, the authors have analyzed some of the variables involved in the preparation of resin bases for removable prostheses. Various polymerization methods were tested: --the pressed technique: standard and Acron MC systems; --the injection technique: SR-Ivocap and Unipress systems. They were thus able to demonstrate the effect of the chemical composition on the homogeneity of the microscopic surface structure of the resins. They also pointed out that some of the muffle systems induce visible strains on the macroscopic surface structure. Besides, they observed that the polymerization cycle does not modify the microscopic surface structure of the resin. In conclusion, they advocate the use of resins with a chemical composition fitted in systems inducing minimum tensions. PMID- 2239411 TI - [Drug interactions in dentistry]. AB - The authors describe the various interactions which may exist between the medical treatments followed by patients and various groups of substances used in odonto stomatology: non-steroid anti-inflammatory drugs, antibiotics, antifungicides, vasoconstrictors and local anaesthetics. They clarify the clinical risk relating to each of these medicament interactions. PMID- 2239412 TI - [Immediate placement of an implant after extraction: indications and surgical requirements]. AB - Following the extraction of a tooth, a 3 to 6 months period of healing is generally necessary before a screwed or impacted titanium implant can be placed. After what, another 3 to 6 months period is necessary before it is possible to expose the implant and put it to function. Nonetheless, in some clinical situations, and under certain surgical conditions, it has become apparent that the immediate positioning of an implant after extraction is currently possible and even recommended, thus ensuring an aesthetic and psychological advantage for the patient. PMID- 2239413 TI - [Medical treatment of epulis by local injection penicillin therapy]. AB - Treatment in November 1987, of an epulis-type gingival tumor, with in situ penicillin G injections, resulted in complete eradication of this benign tumor with no recurrence more than one year later. This case-report may be added to others of the same type reported by Dr. Joseph ABRAVANEL: since 1978, date of the first presentation at the "Hospital Necker Scientific Meeting", all cases treated (approximately ten) resulted in complete cure without any recurrence; the cases reported in 1978 were all followed and there was no recurrence. Since this technique demonstrated a superior efficacy over Surgery, we decided to report this last case with a follow-up period exceeding one year. However, we are aware, in spite of the long follow-up and the constant results, of the limited number of cases in the study. We hope that, with the help of all our colleagues, we will be able to improve our results. The mechanism of action of penicillin G opens a number of prospects in the pathology of the oral mucosa, especially iatrogenic pathologies: Cyclosporine, Dihydan, etc. PMID- 2239414 TI - [Correction of upper impacted canines in vestibular position with segmental osteotomy advancing the incisal block. Apropos of 5 cases]. AB - The author reports on 5 cases of segmental osteotomy advancing the upper incisal block, in the treatment of vestibular retention of an upper canine associated with an upper retro-alveolitis and/or brachypremaxillitis. This surgery is proposed as an alternative to the extraction of the 4 pre-molars, which is usually done in these cases of apparent disharmony. PMID- 2239415 TI - [Mandible and its image, thought on cephalometry]. AB - Starting with the mandible, chosen as a pretext, the author of this book thinks about the necessity of its shape as it is observed by anatomists and orthodontists; he draws conclusions which lead him to have reservations as to the kind of thinking which impel most of the methods of cephalometric analysis and argues for a new "look" in imaging. PMID- 2239416 TI - [Mandibular osseous lacuna, salivary inclusion]. AB - Salivary inclusion is seen, on panoramic films of the maxilla and the mandible, in the form of a mandibular osseous lacuna. Such an indicative diagnostic image, the prognosis for which is often sobering, requires CT scan exploration. The latter permits the diagnosis of Stafne's lacuna, the nature of which is benign. Quick and sure. PMID- 2239417 TI - [Evaluation of time needed to treat periodontal conditions classified according to the C.P.I.T.N. index]. AB - A questionnaire was sent to 623 members of the "French Society of Periodontology" with a view to assessing the time necessary to provide instructions concerning hygiene, carry out root planing, surgery on 3.5 to 5.5 mm pockets, surgery on pockets of 6 mm or more, and to ensure maintenance. 282 responses were received from the practitioners and were computer analysed. The time required for instructions concerning hygiene was estimated to be approximately 15 mn. This information was usually repeated 4 times. It was determined that scaling and root planing require an average of 29.19 mn per sextant. The surgical interventions for 3.5 to 5.5 mm and 6 mm or more pockets are estimated to last an average of 77.03 and 107.36 mn respectively. Finally, the assessment of the time necessary for maintenance of the whole mouth was 30 to 60 mn, with an average of 45.11 mn. A quarterly check-up was recommended by 48.9% of the practitioners. The treatment of complex cases requires much more time, and maintenance is indispensable in order to avoid relapse. A plaque control programme undertaken sufficiently early might avoid long treatment stages. PMID- 2239418 TI - [Importance of diabetic equilibrium in periodontal condition. Clinical study]. AB - Three hundred forty diabetic adults were examined. Initially 39 well equilibrated diabetic patients (W.E.D.), with Hb A 1C less than or equal to 6% and 301 poorly equilibrated diabetic patients (P.E.D.) with Hb A 1C greater than 6% were involved. During a second phase, 60 moderately well equilibrated diabetic patients (M.W.E.D.) were counted with Hb A 1C less than or equal to 7% and 280 poorly equilibrated diabetic patients (P.E.D.) with Hb A 1C greater than 7%. The teeth examined were 16, 21, 24, 36, 41 and 44. The indices used were Pl. I. and G.I.; the depths of the pockets were measured. The gingival fluid was sampled from 21 and 24. There was no influence of equilibrium on the Pl. I., G.I., depth of the pockets and the gingival fluid, or any correlation between Hb A1C and the four criteria chosen. The equilibrium of a diabetic patient, whether it be perfect or mediocre, does not seem to influence the periodontal condition. PMID- 2239419 TI - Seventh annual meeting. Singapore, November 4-11, 1990. Abstracts. PMID- 2239421 TI - Circulating regulatory factors and neuroendocrine function. Proceedings of a symposium. June 26-July 1, 1989, Smolenice Castle, Czechoslovakia. PMID- 2239420 TI - The tuberoinfundibular dopaminergic neurons of the brain: hormonal regulation. AB - The role of prolactin and of estradiol and progesterone in the control of the biosynthetic and secretory activity of TIDA neurons has been investigated in the following animal models: young female rats, aged female rats, and young male rats. The indices of TIDA neuronal function employed were a) mass of TH in neurites in the ME, b) total in situ activity of TH in the ME, c) in situ molar activity of TH in the ME, and d) secretion of dopamine into hypophysial portal blood. It was found that prolactin in high concentration in the circulation and in the CSF had little, if any, effect on the mass of TH in the ME. However, a high concentration of prolactin in either the circulation or in the CSF stimulated significantly the in situ TH activity in the ME whether expressed in terms of total activity per ME or activity per mole of TH. The stimulation of TH activity with prolactin was prevented by immunoneutralization of circulating prolactin. A high concentration of prolactin in the CSF was as effective in stimulating TH activity in the ME of rats with intact pituitary glands as in hypophysectomized rats. In addition to prolactin, treatment of animals with intact pituitaries with a combination of estradiol and progesterone markedly stimulated the total in situ activity of TH of the ME as well as the in situ molar activity of TH of the ME, but neither estradiol nor progesterone alone had an effect on TH activity. Hypophysectomy abolished the stimulatory action of estradiol and progesterone on TH activity of the ME. In addition to the in situ activity of TH in the ME, estradiol-progesterone treatment stimulated the secretion of dopamine into hypophysial portal blood. Neither estradiol nor progesterone alone affected dopamine secretion by TIDA neurons. We conclude that exposure to high concentrations of prolactin or to both estradiol and progesterone stimulate the biosynthetic and secretory activity of TIDA neurons. These hormones are effective in old rats and well as young rats and in males as well as females. PMID- 2239422 TI - Regulation of the sympathetic nervous system by circulating vasopressin. PMID- 2239423 TI - Antibodies to neuropeptides: biological effects and mechanisms of action. PMID- 2239424 TI - Circulating corticotropin-releasing factor in pregnancy. PMID- 2239425 TI - Central action of adrenal steroids during stress and adaptation. AB - Corticosteroids interact with receptors in the central nervous system. These receptors display heterogeneity and can be distinguished as corticosterone- and aldosterone-binding mineralocorticoid receptors and dexamethasone-binding glucocorticoid receptors. Ligand specificity of mineralocorticoid receptors for either corticosterone or aldosterone seems to be determined by co-localized transcortin and the enzyme, 11 beta-hydroxysteroid dehydrogenase. Aldosterone selective mineralocorticoid receptors appear to be present in the circumventricular organs and the AV3V region of the hypothalamus and mediate behavior that is driven by salt appetite. Highest concentrations of mineralocorticoid receptors are found in neurons of the hippocampus. These limbic mineralocorticoid receptor sites mediate tonic influences of corticosterone on brain processes. Glucocorticoid receptors bind corticosterone with a tenfold lower affinity than do mineralocorticoid receptors, and are widely distributed in neuronal and glial cells of the brain. Glucocorticoid receptors are involved in the termination of the stress response (negative feedback). Studies involving measurement of glucocorticoid receptor mRNA and binding sites have revealed that glucocorticoid receptors are subject to autoregulation. After ADX, glucocorticoid receptor concentration increases, but is reduced after chronic stress, chronic administration of glucocorticoids, and at senescence. A diminished glucocorticoid receptor concentration may compromise the negative feedback action exerted by glucocorticoids after stress. After ADX, mineralocorticoid receptor binding is acutely up-regulated and reaches its maximum between 7 and 24 hours post-ADX. Mineralocorticoid receptor mRNA level shows a transient increase following ADX. Long-term ADX has no effect on the mineralocorticoid receptor concentration, but, interestingly, chronic dexamethasone treatment results in an up-regulation of mineralocorticoid receptors. Mineralocorticoid receptor level is decreased at senescence, but this age-related decrement can be reversed by chronic treatment with the ACTH4-9 analog, ORG 2766. Functionally, mineralocorticoid receptors and glucocorticoid receptors are involved in different aspects of the organization of the stress response, and in conjunction they control the stress responsiveness of the animal. PMID- 2239426 TI - The physiology of the blood-brain barrier. AB - The BBB is a dynamic interface between blood and the central nervous system enabling the brain to keep an optimal internal environment. The endothelial cells of the brain capillaries are unique epithelial-like cells that are fused together by tight junctions and have a low pinocytotic activity. The entry of a specific substance will, therefore, mainly depend on its lipid solubility, and whether or not it has access to any of the carriers in the endothelial cells. Enzymatic degradation in the endothelium can prevent entry into the brain of substances that do enter the endothelial cells. Astrocytes may have an important role by inducing and upholding some barrier functions. An intact BBB is evidently important for optimal brain function. Manipulation of the BBB to allow entry of therapeutic agents may be justified under certain circumstances but should be done with caution until we know more about the long-term consequences of such manipulation. PMID- 2239427 TI - Effects of thyroid hormones on the hypothalamic dopaminergic neurons. PMID- 2239428 TI - Inhibin and related proteins: localization, regulation, and effects. AB - Inhibin has originally been defined as a gonadal hormone that exerts a specific negative feedback action on the secretion of FSH from the gonadotropic cells of the pituitary gland. The existence of inhibin was postulated by Mottram and Cramer (15) as early as 1923. However, only after reliable and sensitive bioassay systems had been developed for detection and estimation of inhibin and an ample source of inhibin was found in the form of ovarian follicular fluid, was progress made on the isolation and characterization of the hormone. It is apparent now that inhibin, which itself consists of a dimer of two different subunits, alpha and beta, is a member of a much larger family of (glyco)protein hormones and growth factors that includes Mullerian inhibiting substance, transforming growth factor-beta, activin/erythroid differentiation factor, bone morphogenetic proteins, and an insect and a Xenopus protein. All play important roles in cell differentiation. Gonadal inhibin is produced in the Sertoli cells in the testis and in the granulosa cells in the ovary. The production of inhibin is stimulated by FSH, but controversy exists about other factors that might play a role in the regulation of the production of inhibin. It appears likely that inhibin plays an important role in the feedback regulation of peripheral concentrations of FSH during the period in which Sertoli cells and granulosa cells--the target cells for FSH--divide, i.e., during puberty in male animals and during the development of ovarian follicles in female animals. In this way, inhibin may be an important regulator of the number of developing Sertoli cells and of the length of the seminiferous tubuli in the testis and of the number of developing follicles in the ovary. Apart from its function in the pituitary-gonadal axis, inhibin and activin may be produced and act in a number of other organs such as the placenta, hypothalamus, adrenal, and bone marrow. Investigation of the role of the members of the inhibin family in these systems has only begun, but will certainly be a field of major interest in the near future. PMID- 2239429 TI - Neuroendocrinology of interleukin-1. PMID- 2239430 TI - Role of monokines in control of anterior pituitary hormone release. AB - It has long been known that endogenous pyrogen, released as a result of injection of typhoid vaccine or in response to infection, produces fever and increases ACTH secretion. Recent studies have indicated that endogenous pyrogen is, at least in part, IL-1. This monokine has now been shown to activate the release of ACTH by a hypothalamic mechanism with release of CRF and possibly vasopressin, which stimulates the corticotrophs. There may also be a pituitary action to stimulate the release of ACTH directly. In our experiments we showed that IL-1 at low but not higher doses appears to act intrahypothalamically to stimulate GH and PRL release and to inhibit TSH release. In the meantime, another monokine, cachectin, was isolated and its structure determined. We have found that this monokine can act following its third ventricular injection to stimulate ACTH, PRL, and GH release and to inhibit TSH release, at least in part, by release of prostaglandins since indomethacin, an inhibitor of prostaglandin synthesis, produced a blockade of the responses except for those of ACTH. This peptide also has highly potent effects to alter pituitary hormone release by direct action on the pituitary to stimulate ACTH, GH, and TSH and to a slight extent PRL release. These actions appear to involve prostaglandins since indomethacin blocks all of the effects except for the effect on ACTH secretion. This monokine also produces a dose-related lowering of anterior pituitary cyclic AMP levels. When the monokine was incubated along with somatostatin, the lowering of cyclic AMP was reversed, and a potent PRL-releasing effect of the monokine was visible. We have begun studies with a third monokine, gamma interferon, which indicate that it stimulates ACTH release but suppresses plasma GH and TSH levels by a hypothalamic action. It is apparent that these various monokines have powerful effects to alter hypothalamic-pituitary function and that they probably mediate most of the effects of infections on the release of anterior pituitary hormones. PMID- 2239431 TI - Interleukins, signal transduction, and the immune system-mediated stress response. AB - Overwhelming evidence indicates that the administration of cytokines such as IL-1 alpha and beta, IL-6, and TNF-1 alpha stimulates one or more components of the HPA axis. The hypothesis driving this research is that host infection and tissue injury trigger the synthesis and release of several cytokines that act locally at sites of trauma and distally upon entering the circulation. Available evidence suggests that the primary source of HPA axis-acting or circulating cytokines is activated monocytes or macrophages; therefore, a direct relationship should exist between the appearance of monokines in plasma and the subsequent appearance of pituitary-adrenocortical hormones in plasma as well. Clarification of the physiological role of monokines as mediators of the host stress response will come from in vivo studies in which the type, sequence of appearance, duration of elevation, and quantification of each monokine is monitored along with ACTH and glucocorticoids, following an appropriate immune challenge. In several recent reports, investigators have administered bacterial-derived endotoxin or LPS to stimulate the physiological events associated with infection or injury and chronicled plasma levels of IL-1, IL-6, and TNF-alpha (37,56,57). In human subjects, endotoxin challenge enhanced plasma TNF-alpha levels by 1 hour, which returned to basal levels by 4 hours (37), whereas, IL-6 plasma activity increased at 2 hours post-challenge and returned to baseline by 6 hours (56). Thus, both of these monokines are implicated as possible acute activators of the HPA axis. In perhaps the most revealing study to date, LPS challenge of mice indicated both a differential appearance and disappearance rate in serum for TNF-alpha and IL-1 and a differential regulation of these monokines by glucocorticoid feedback (57). Serum TNF was detected 45 minutes post-LPS, peaked by 1 hour, and returned to control levels by 3 hours. Serum corticosterone concentrations rose rapidly over a time course similar to that of TNF. Even after serum TNF concentration had returned to basal conditions, corticosterone levels remained maximally elevated, and serum corticosterone was still significantly above basal levels 24-hour post LPS. The rapid return of circulating TNF to pre-LPS challenge levels appeared to be regulated by negative glucocorticoid feedback, because TNF remained maximally elevated for at least 6 hours in adrenalectomized or hypophysectomized mice. LPS induced levels of IL-1 were delayed as compared to serum TNF, peaked at 4 hours, and remained elevated even at 24 hours.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2239432 TI - Immunoneurology: a serum protein afferent limb to the CNS. PMID- 2239433 TI - Neuroendocrine mechanisms in the thermogenic responses to diet, infection, and trauma. PMID- 2239434 TI - The blood-brain barrier in diabetes mellitus. PMID- 2239435 TI - Circulating blood glucose and hypothalamic-pituitary secretion. PMID- 2239438 TI - Exchange of peptides between the circulation and the nervous system: role of the blood-brain barrier. PMID- 2239437 TI - Blood-brain barrier and neuroendocrine regulations. PMID- 2239436 TI - Nutritional and hemodynamic factors influencing adenopituitary function in man. PMID- 2239439 TI - Vasopressin, the blood-brain barrier, and brain performance. PMID- 2239440 TI - Macrophage phospholipase A2 activity and eicosanoid production: studies with phospholipase A2 inhibitors in P388D1 cells. PMID- 2239441 TI - Phospholipase A2--role and function in inflammation. Based on the proceedings of the Symposium on Phospholipase A2: Pathophysiological Role of Soluble and Membrane-Bound Enzymes. January 15, 1989, New York, New York and the Federation of American Societies for Experimental Biology Symposium on the Release and Function of Phospholipase A2. March 22, 1989, New Orleans, Louisiana. PMID- 2239442 TI - Mobilization and function of extracellular phospholipase A2 in inflammation. PMID- 2239443 TI - Cellular and extracellular phospholipase A2 activity in zymosan pleurisy in rat. AB - The pleural exudate from rats treated intrapleurally with zymosan contains phospholipase A2 (PLA2) activity which is Ca2(+)-independent and optimally active at a neutral pH. This PLA2 activity was found in approximately equal amounts in both the cellular and extracellular fractions of the exudate. The Ca2(+) independency of the PLA2's in the pleural exudate distinguishes them from plasma PLA2's and this suggests that the source of the exudate PLA2's is not plasma. The appearance of PLA2 activity in zymosan-induced pleural exudate correlates temporally with increases in exudate volume and pleural cell number. In all cases, the maximum response was seen 24 hr after zymosan challenge. All parameters of pleurisy and PLA2 activity are similarly sensitive to the steroid dexamethasone which has been hypothesized to act, in part, through the synthesis of PLA2 inhibitory peptides. In its entirety, this information suggests that there is a relationship between pleural PLA2 activity and the appearance of pleural inflammation (exudate volume and cells) and that PLA2 may play an important role in the initiation and propagation of this inflammatory process in rats. Furthermore, the zymosan-induced pleurisy model may serve as a useful model for the identification of PLA2 inhibitors with antiinflammatory activity. PMID- 2239444 TI - Pharmacological control of phospholipase A2 activity in vitro and in vivo. PMID- 2239445 TI - Localization and evolution of two human phospholipase A2 genes and two related genetic elements. AB - Mammals are now known to contain at least two distinct classes of phospholipases A2, the progenitors of which can be seen in the venoms of snakes. Mammalian "Type I" PLA2, synthesized primarily by the pancreas, is also present in smaller amounts in other tissues including lung, spleen, and kidney. Recently, a mammalian "Type II" PLA2 has been sequenced, and shown to occur in platelets, synovial cells and fluid, cells of inflammatory peritoneal exudate, liver, intestine, kidney, and placenta. This form, referred to here as Type IIA PLA2, could play a key role in arachidonate release in both normal and pathologic inflammation. The genes encoding both forms have also been recently cloned. Here, the sites of synthesis and respective roles of the two known enzymes are discussed, along with an analysis of the evolutionary conservation of Type IIA PLA2 gene sequence. In addition, two related genetic elements containing sequences homologous to a portion of Type II PLA2 are described, which map to the same chromosome as the Type IIA PLA2 gene (chromosome 1). Either or both of these could also encode a portion of additional mammalian PLA2s. PMID- 2239446 TI - Structure and properties of a secretable phospholipase A2 from human platelets. PMID- 2239447 TI - Phospholipase A2 activation is the pivotal step in the effector pathway of inflammation. AB - Our understanding of the mechanisms of initiation and propagation of local and systemic inflammatory processes is clearly imperfect if one uses the available therapeutic modalities as a yardstick. While glucocorticoids are potent anti inflammatory drugs, the pharmacologic target of this class of agents has not been identified with certainty, and the use of steroids is fraught with the risk of considerable and potentially dangerous side effects. On the other hand, non steroidal anti-inflammatory drugs (NSAIDS), while more specific, are relatively weak anti-inflammatory compounds and frequently require the addition of more potent agents. Cytotoxic drugs or anti-metabolites effectively suppress acute and chronic inflammatory reactions, but also predispose to infection and initiate the development of neoplasms following long-term exposure. The inadequacy and relative non-specificity of these approaches underscore the deficiencies in our understanding of the principles that govern these responses. A better understanding of these processes will be applicable to broad categories of human disease including autoimmunity, the collagen vascular diseases, aberrations in host defense and the response to trauma and infection. PMID- 2239449 TI - Activation, structure, and organization of genes involved in microbial defense in plants. PMID- 2239448 TI - Response of plant antioxidant defense genes to environmental stress. PMID- 2239450 TI - Molecular and cellular biology of the heat-shock response. PMID- 2239451 TI - Effects of heat and chemical stress on development. AB - Similarities in the means by which developmental defects are induced in vertebrates and Drosophila suggest that some kinds of defects may be induced by similar mechanisms. The similarities include the fact that heat and a group of chemicals that induce synthesis of heat-shock proteins induce defects in mammals, chickens, and flies. Different kinds of defects are even produced in one type of animal, depending on the precise timing of the environmental insult. The effectiveness of the environmental treatment in inducing defects depends on the genetic background of the animal as well as on past exposure to chemicals and heat. Developmental defects induced by heat in mice, rats, and flies can all be prevented by thermotolerance-inducing treatments. The basis for these effects has been studied at the molecular level in Drosophila, and the evidence indicates that these teratogens and the thermotolerance-inducing treatments affect the level or timing of expression of specific genes during critical periods in the developmental program. PMID- 2239453 TI - Cholinergic muscarinic binding of blood lymphocytes in patients with Parkinson's disease. PMID- 2239452 TI - Neurotrophic factors and Parkinson's disease. PMID- 2239454 TI - Brain glucose metabolism in Parkinson's disease. PMID- 2239455 TI - Superoxide dismutase-like activity in the Parkinson's disease brain. PMID- 2239456 TI - The "serotonin hypothesis" for depression in Parkinson's disease. PMID- 2239458 TI - Kinematic properties of upper-limb trajectories in Parkinson's disease and idiopathic torsion dystonia. PMID- 2239457 TI - Conditioning transcranial cortical stimulation (TCCS) by exteroceptive stimulation in parkinsonian patients. PMID- 2239459 TI - Precision grip in parkinsonian patients. PMID- 2239461 TI - Behavioral and biochemical effects of 4-phenylpyridine, 2-phenylpyridine, and 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine in rodents. PMID- 2239460 TI - Age, environments, and the number of substantia nigra neurons. AB - We examined forty-eight midbrain sections from normal brains containing SN at the level of the exiting fibers of the IIIrd cranial nerve. The cases were classified into two groups based on at least 80% life exposure to either rural or urban provincial environments, respectively. Linear regression analysis revealed a lower SN neuron count in the rural group by age 20, although this difference was not statistically significant. There was a 34% decline in urban and a 17% decline in rural residents' neuron counts between ages 20 and 80. These results are consistent with our previous studies, which indicate a higher risk of PD in the Saskatchewan rural population. We believe that studies of environmental factors in early life will provide the most rewarding clues to the etiology of PD. PMID- 2239462 TI - Interference of 3-O-methyldopa with L-dopa treatment for MPTP-induced parkinsonism in mice. PMID- 2239463 TI - Research diagnostic criteria for Parkinson's disease. PMID- 2239464 TI - Muscular weakness in Parkinson's disease. PMID- 2239465 TI - Psychogenic tremors. PMID- 2239467 TI - Progressive supranuclear palsy: motor, neurobehavioral, and neuro-ophthalmic findings. PMID- 2239466 TI - Cerebrospinal fluid dopamine, norepinephrine, and epinephrine concentrations in Parkinson's disease correlated with clinical symptoms. PMID- 2239468 TI - Parkinson's disease and hydrocephalus. PMID- 2239469 TI - Do parkinsonians exhibit visuospatial deficits? PMID- 2239470 TI - Shifting ability in Parkinson's disease: does shifting ability really deteriorate? PMID- 2239471 TI - Parkinson's disease and the frontal hypothesis: task alternation in verbal fluency. PMID- 2239472 TI - Aspects of language in parkinsonism. PMID- 2239473 TI - Premorbid personality and idiopathic Parkinson's disease. PMID- 2239474 TI - The premorbid personality of patients with Parkinson's disease: a comparative study with healthy controls and patients with essential tremor. PMID- 2239475 TI - Risk factors for dementia in Parkinson's disease. PMID- 2239476 TI - Psychosocial problems of Parkinson patients: approaches to assessment and treatment. PMID- 2239477 TI - Parkinson's disease, motoneuron disease and Alzheimer's disease: origins and interrelationship. AB - The cause of neurodegenerative disease is considered. For Alzheimer's disease, Parkinson's disease, and motoneuron disease, accumulating evidence over the last 3 years indicates that (a) the usual etiological mechanisms involve a subclinical lesion which kills some neurons and reduces the life expectation of their surviving neighbors, and (b) there may be more than one cause for each of the idiopathic syndromes now termed AD, PD, and MND. PMID- 2239478 TI - Motor response complications with chronic levodopa therapy. PMID- 2239480 TI - Longitudinal study of effects of early levodopa treatment on disability and mortality in Parkinson's disease. PMID- 2239479 TI - Utilization of antiparkinsonian drugs in Sweden, 1974-1987. PMID- 2239482 TI - Parkinson's disease mortality: preliminary report. PMID- 2239481 TI - Psychiatric complications and shift of death age in Parkinson's disease. PMID- 2239483 TI - Bromocriptine and levodopa in early combination in Parkinson's disease: first results of the Collaborative European Multicentric Trial. PMID- 2239485 TI - Autonomic nervous system disturbances in Parkinson's disease. PMID- 2239484 TI - Vitamin E therapy in Parkinson's disease. PMID- 2239486 TI - Levodopa treatment of Parkinson's syndrome: past and future. PMID- 2239487 TI - Madopar HBS (hydrodynamically balanced system) in the treatment of Parkinson's disease. PMID- 2239488 TI - Inhibitors of dopamine inactivating systems as antiparkinson drugs. PMID- 2239489 TI - Catechol-O-methyltransferase and its role in catecholamine metabolism. PMID- 2239490 TI - Ro 40-7592, a novel, very potent, and orally active inhibitor of catechol-O methyltransferase: a pharmacological study in rats. PMID- 2239491 TI - Clinical and pathological features of corticobasal degeneration. PMID- 2239492 TI - Controlled-release dopamine polymers as a novel approach to the treatment of Parkinson's disease. PMID- 2239493 TI - Madopar HBS in nocturnal symptoms of Parkinson's disease. AB - Madopar Hydrodynamically Balanced System (HBS), a new sustained-release levodopa preparation, was used to control severe nightly disabilities in 15 outpatients suffering from Parkinson's disease in an advanced state and with long-term levodopa therapy. This medication was given ante noctem in addition to an otherwise unchanged daily regimen of levodopa administration. In 13 patients a considerable diminution in nocturnal akinesia and in the frequency of waking up was reached with a mean dosage of 308 mg of Madopar HBS. Early morning akinesia was only slightly alleviated in four patients. The nocturnal off-period pain disappeared in one patient. Adverse effects consisted of nocturnal dyskinesia in two patients and early morning dystonia in another two patients. The regular use of sleeping pills was clearly reduced after Madopar HBS therapy. PMID- 2239494 TI - Clinical experience with cabergoline, a new ergoline derivative, in the treatment of Parkinson's disease. PMID- 2239495 TI - The clinical benefit of NADH as stimulator of endogenous L-dopa biosynthesis in parkinsonian patients. PMID- 2239496 TI - Adrenal neural transplants in Parkinson's disease. PMID- 2239498 TI - Adrenal medullary tissue transplantation in Parkinson's disease: a review. PMID- 2239497 TI - Adrenal medullary transplants as a treatment for Parkinson's disease. PMID- 2239499 TI - Methods in teaching consultation-liaison psychiatry. PMID- 2239500 TI - Consultation-liaison models for teaching psychiatry to primary care physicians. PMID- 2239501 TI - Models for the assessment of clinical performance in consultation-liaison services. PMID- 2239502 TI - Models for research in consultation psychiatry. PMID- 2239504 TI - Training issues at the interface between consultation-liaison psychiatry and behavioral medicine. PMID- 2239503 TI - A family-systems model for consultation psychiatry. PMID- 2239505 TI - Consultation-liaison education in a community hospital setting. PMID- 2239506 TI - The three-function model of the medical interview. An educational device. PMID- 2239507 TI - Training physicians in the clinical evaluation of the suicidal patient. PMID- 2239508 TI - [Birth weight of newborn infants in relation to body height and body weight of parents with special reference to duration of pregnancy]. AB - Using the data of the 1985 GDR somatogram standards (birthweight percentiles calculated from 51,570 liveborn singletons) the impact of parental weight and length on the birthweight were calculated. Peristatic factors in combination with the genetic 'anlage' act first of all via maternal weight. Body height and/or length of mother and father are more representative for the genetic constitution. Their impact on neonatal weight seems to be less significant, however statistically calculable. The paternal 'anlage' is relatively modified by the intrauterine environment (maternal constitution). PMID- 2239509 TI - [Psychophysical prerequisites and mental performance of school children]. AB - By extensive investigations and statistical calculations it is possible to establish the psychophysical prerequisites for performance, which consist of "mental processing speed" and "vegetative reactivity". These can be developed by training and thus contribute to improved mental performance. PMID- 2239510 TI - [Early psychological diagnosis in children with brain damage]. AB - Considerations of the essential aspects of establishing diagnosis are explained fro a psychologist's point of view who has the possibility of observing the course of all children with cerebral injury registered early in the district polyclinic. Their qualitative performance parameters are evaluated, especially attention and the mother-child relation. Subsequently, we discuss the courses of development for 130 children who attended a rehabilitation nursery, and refer to constellations of symptoms which rendered it more difficult to establish early diagnoses. PMID- 2239511 TI - [Longitudinal study of early intervention, clinical course and school performance of mildly retarded kindergarten children]. AB - Two groups of 6-8 children aged 3-4 years with a mental retardation of 6 to 9 months were educated in special Kindergarten groups for one year. The effects were checked three times during the year and in the children's third or fourth year at school. A control group matched for age and mental development continued in the Kindergarten as usual and was checked in the same way. As we had supposed, the children in the small groups demonstrated better results in their mental and behavioural development after one year of special education. There was also some evidence that it had a positive effect up to the age of 10 years. The positive effect on their behaviour was more pronounced (according to psychological examinations, school marks and questionnaires for teachers and mothers) than on their intellectual performance. Thus, special education in small groups can promote a more harmonious development of the personality of slightly retarded children. PMID- 2239512 TI - [Psychophysical status of high school graduates. Results of sociologic studies]. AB - This article intends to describe the present state and development of the psychophysical state of health of GDR graduates. Special attention is given to various quantities influencing the state of health, above all job-related determinants. The empirical basis is an interval study, carried out by the Zentralinstitut fur Jugendforschung Leipzig; this study registered and attended hundred of people from the beginning of their studies in 1970 during the following 15 years in seven intervals. Preferably social factors and determinants were studied empirically and partly problematical interrelations between health and working conditions and contents as well as critical development trends of health were pointed out. In this way important starting points for taking measures to influence exogene health determinants were fixed: especially questions of working contents, of correct appointment of graduates corresponding to their profession and qualification, of a permanent training of psycho-physical capabilities. PMID- 2239513 TI - [Effects of health education intervention on the physical activity of adolescents]. AB - A report is given about the results of physical activities in spare time and the physical capacities of 967 pupils of the 7th to 10th form. These pupils were asked and examined in 1987 in the country of Hohenmolsen. Particularly, the results are compared with the basic investigation on pupils of the same age in 1983. Nearly half of the pupils finished an interventional programme. The other part served as a control group. The comparison of both cross-section investigations even as the statements of a longitudinal-section study and a cross section study from 1985 documented a good up to a very good increase of physical activities in spare time and physical capacities with regard to the complex test and long-distance race, especially at girls. The control group also shows an increase of the examined parameters. Finally, aspects for the improvement of the results in both groups are discussed. PMID- 2239515 TI - Facial disfigurement: problems and management of social interaction and implications for mental health. AB - The concern of this article is with the impact of facial disfigurement on social interaction during brief encounters, the ramifications of which have the potential for psychological and social destruction. Largely ignored by those interested in the social and psychological problems and rehabilitation of the functionally impaired, such as the blind, the deaf, the amputee, the intent here is to point up the major problems associated with facial disfigurement and to explore some of the ways of dealing with them. The data on which this article is based were collected over many years and are no longer new, but this attempt to synthesize them for a particular purpose is. PMID- 2239514 TI - Dermal and subdermal tissue filling with fetal connective tissue and cartilage, collagen, and silicone: experimental study in the pig compared with clinical results. A new technique of dermis mini-autograft injections. AB - The early reaction to the injection of silicone, collagen, and lyophilized heterologous fetal connective and cartilage tissues into the limiting zone deep dermis-superficial subcutaneous tissue was histologically examined in the pig and compared with clinical results. The inflammatory reaction to lyophilized heterologous fetal tissue is considerably more intense than that to collagen and silicone and lasts for several weeks. Therefore, it is not recommended for soft tissue filling in the face. Admitting an inferior antigenicity of fetal tissues, the authors suggest that enzymatically denaturalized collagen should be manufactured from heterologous fetal connective tissue, to be then further tested. The reaction of tissue to silicone and collagen is minimal. Silicone is preferred for dermal injections since in clinical experience it remains in the site of injection much longer. For subdermal injections, however, collagen is preferred. Based on experience with over 600 patients since 1958, the first author continues using liquid silicone. The lack of complications is probably a result of the fact that only small amounts (milliliters) of silicone were used in wrinkles or small depressions in the dermal layer and that from the beginning injection into the subcutaneous tissue was avoided. Since 1988 a new technique for the treatment of wrinkles and skin depressions with injections of dermal miniautografts has been used with satisfactory results. PMID- 2239516 TI - Circumferential liposuction of calves and ankles. AB - Calf and ankle liposuction was performed on 110 patients for a total of 166 cases. Only 84% of these patients were satisfied with the results compared with 98% of those who underwent liposuction in other parts of the body. The author presents statistics and explains the criteria used to select patients for treatment. Selection is partly based on the preoperative thickness of subcutaneous fat. He also outlines the minimum amount of fat that should be reserved to avoid postoperative skin irregularity. The difficulties encountered during liposuction that are caused by the anatomical characteristics of the calves and ankles are discussed, and suggestions for solving such problems are presented. The author also describes special instruments he designed. PMID- 2239517 TI - Suction-assisted lipectomy of the upper arm: a four-cannula technique. AB - A new technique for suction-assisted lipectomy of the upper arm is described. It uses four separate cannulas of varying lengths, all with an internal diameter of only 3.0 mm. Only a single incision is required. The benefits include the elimination of the complication of excessive fat suctioned from the middle of the arm, reduced scarring, and reduced surgical time. The patient recovers quickly with less bruising and more comfort. Results are pleasing with virtually no complications. PMID- 2239518 TI - Aesthetic improvement of the forehead utilizing methylmethacrylate onlay implants. AB - Forehead augmentation occasionally is necessary for obtaining a desirable upper facial contour. The final contour must be sexually appropriate and must project beyond the cornea of the eyes an amount that makes the contour aesthetically pleasing. Methylmethacrylate onlay implants, preformed or sculpted at the time of surgery, lend themselves to obtaining a desirable contour which can be modified easily at surgery, which is completed in a one-stage procedure, has few complications, and yields an aesthetically pleasing result. The methods for fabricating and implanting the onlay prosthesis in a single step and the results of such procedures, which have been performed over a 12-year period without complications, are presented. PMID- 2239519 TI - Dye laser treatment of port-wine stains. AB - The author treated 456 cases of port-wine stains using a tunable dye laser (577 nm wavelength, 1-microsecond pulse, 2-3-mm diameter spot), and followed up 22 cases for a year or more after the initial treatment. The treatment was regarded as effective in 80.5% of the abnormal lesions. The results were influenced by location: good results were achieved in the neck region and face, but results in the extremities were poor. The dye laser can achieve selective injury to abnormal vessels of port-wine stains while inflicting less damage to the overlying dermis than the argon laser. Therefore, dye laser treatment for port-wine stains is more effective than argon laser treatment. PMID- 2239520 TI - An improved draping method for otoplastic surgery. AB - An alternative method of draping of the ears is presented in which a mesh gauze dressing is used as an adjunctive method for restraining hair from the surgical field. Its use is rapid and permits exposure and visibility of the ears bilaterally. PMID- 2239521 TI - Patients seeking symmetrical recontouring for "perceived" deformities in the width of the face and skull. PMID- 2239522 TI - Early history of lipoplasty in the United States. PMID- 2239523 TI - A critical look at blood samples in CB and COAD. AB - Few studies have utilized measurements of blood variables to estimate the clinical activity of chronic bronchitis in relation to clinical trials. In one study, we have followed such patients with repeated measurements of serum levels of lactoferrin, myeloperoxidase and lysozyme as markers of neutrophil and monocyte/macrophage activity. We showed that these patients have raised lysozyme levels, as signs of ongoing activation of the macrophage population, irrespective of the presence of infectious exacerbations. Lactoferrin and myeloperoxidase levels, on the other hand, showed large variations with peaks mostly coinciding with the infectious exacerbations. In another study, we made repeated measurements during a 6-months' period of a number of neutrophil activities. These data showed increased activities with respect to migration and oxidative metabolism during the period of increased numbers of infectious exacerbations. All but one variable became normal during periods of few infectious. Thus, the lucigenin-enhanced chemiluminescence was subnormal during this period suggesting an abnormality of neutrophil oxidative metabolism in patients with chronic bronchitis. We conclude that the monitoring of markers of inflammatory cell activity in serum may be useful as indicators of the clinical activity of chronic bronchitis and that the measurement of functional activities of the neutrophil is dependent on seasonal variations in the exposure to infectious agents in the community. PMID- 2239524 TI - Airway pathology of functional significance in chronic bronchitis and chronic obstructive airway disease. AB - The three major hypothesis for reduction in the calibre of the peripheral airways in chronic obstructive lung disease are 1) a loss of elastic recoil in the alveolar supporting structure, 2) destruction of the alveolar attachments to the outer wall of the small airways, and 3) a chronic inflammatory process in the wall and lumen of the peripheral airways. This presentation is based on the analysis of an ongoing study where lung function has been measured a few days prior to lung resection. The data collected to date support the third hypothesis and are of interest in developing strategies to treat patients with COAD because they suggest that therapy should be directed at preventing the inflammatory process in the peripheral airways rather than the prevention of lung destruction by emphysema. PMID- 2239525 TI - A critical view on lavage sampling techniques. AB - The constituents of the liquid aspirated in bronchoalveolar lavage are determined by the distribution of the fluid within the bronchial tree, the diffusion through membranes and the dilution by body fluids. Small volume lavages, sample cells, and soluble constituents from the surfaces of the proximal bronchial tree, and usually contain fewer cells than large volume bronchoalveolar lavages. PMID- 2239526 TI - Assessment of soluble parameters in sputum. AB - The concentrations of soluble protein in lung secretions are dependent upon the degree of inflammation, local production and cell activation. Infections and corticosteroid therapy will alter the protein content of lung secretions as a result of their effect on lung inflammation. PMID- 2239527 TI - Sputum cell counts in airway disease: a useful sampling technique. AB - Quantitative sputum cell counts from patients with asthma and chronic bronchitis were performed and found to be reproducible. Sputum from carefully characterized subjects with asthma contained large numbers of eosinophils and formalin sensitive metachromatic (mast) cells. In contrast, the macrophage was the dominant cell type in the sputum from smokers with chronic bronchitis. In a third group of patients with corticosteroid responsive-chronic cough and normal methacholine airway responsiveness the sputum contained eosinophils and metachromatic cells, similar to the asthmatic subjects. Sputum cell counts are a useful, noninvasive method for the identification of this pattern of inflammatory response in patients with airway diseases. PMID- 2239528 TI - Bronchial biopsies in drug intervention studies in CB and COAD. AB - So far, little information is available on the usefulness of the biopsy method in drug intervention studies in COAD and CB. Quantitation studies at electron microscopical level are time consuming. Comparative studies between and within the patient groups are needed to attain basic and clinically relevant information. Pathology studies may lead to a better understanding of basic pathophysiological mechanisms behind the diseases. The sequences of cellular events could be revealed so that morphology may be useful in intervention studies. PMID- 2239529 TI - Inflammatory indices for chronic bronchitis and chronic obstructive airway disease. Cell populations in bronchial and bronchoalveolar lavage. AB - The development of chronic bronchitis (CB) and chronic obstructive airway disease (COAD) seems to be related to inflammatory changes of airway structure. However, the cause and the exact location and type of these changes resulting in altered airway function are not known. Mucosal inflammation is characterized by the recruitment of granulocytes, macrophages and lymphocytes as well as by the shedding of epithelial cells. The present chapter discusses the usefulness of bronchial lavage (BL; 50 ml of lavage volume) directly followed by bronchoalveolar lavage (BAL; 200 ml), for the characterization and quantification of inflammation in proximal and peripheral airways, respectively. On the basis of results from the literature and a pilot study on CB patients with or without coexisting COAD, the following conclusions may be drawn: There is a profound difference in lavage cell composition and numbers between non-smokers and smokers. However, within the group of smokers there are few additional changes in cell numbers and composition when concomitant airway disease is present. The obstruction of the COAD patients is correlated to a reduced recovery of BL and BAL fluid. Furthermore, these patients seem to have a reduced number of most cell types in their BL. This diminitution is not just related to the reduced fluid recovery. The BL cells have a lower viability and BL macrophages have a reduced phagocytic capacity when compared with matching BAL cells. The viability of cells was lowest in BL from the COAD group. These findings may suggest that COAD entails a reduced transport of macrophages to the small airways and/or an enhanced turnover of these cells in the bronchi. Functional studies of lavage cells may supply additional, and perhaps more specific, information on the mechanisms involved in the inflammatory process. PMID- 2239530 TI - The generation of reactive oxygen-derived species by phagocytes. AB - The generation of reactive oxygen-derived species is one main constituent of the microbicidal activity of professional phagocytes. This process is known as the respiratory or the oxidative burst. It is initiated by a cyanide- and azide insensitive increase in O2-consumption and the concomitant generation of superoxide radicals catalyzed by a membrane-localized NADPH oxidase which is triggered by an appropriate stimulation of the cells. The generated O2 is converted to hydrogen peroxide, hydroxyl radicals and other reactive products of oxygen which, if released extracellularly (for example in connection with frustrated phagocytosis), are potentially harmful to the tissue. The oxidative burst is not necessarily dependent on phagocytosis, nor is it necessarily associated with degranulation. Therefore, the process constitutes an important independent variable of phagocyte activity, and researches aiming to characterize various forms of airway inflammation may derive valuable information from an examination of the oxidative burst. PMID- 2239531 TI - Assessment of long-term changes in airway function. AB - There is some evidence supporting long-term 'tracking' of decline in FEV1 at least in middle-aged male smokers, so that a moderately reduced FEV1 predicts subsequent disability and death. Distribution of individual rates of decline in FEV1 stabilizes after follow-up for 4 to 5 years, but large and unexplained differences in decline in FEV1 are found between individuals with similar smoking history. There are theoretical advantages to following post-bronchodilator FEV1 but few studies of its usefulness are available. Changes in other tests derived from the single breath N2 test or the maximum expiratory flow-volume curve have been less informative than originally postulated and their long-term prognostic value remains unknown. PMID- 2239532 TI - Inflammatory indices in chronic bronchitis. Monocyte-macrophage microbicidal activity. AB - Alveolar macrophages are important to the host defence of the lower airways. In smokers and patients with chronic bronchitis, important defects of blood monocyte functions have been identified, which may explain the increased incidence of pulmonary infections in these patients. Upon chronic stimulation, e.g. from tobacco smoke, disease may progress and macrophage activity is probably involved in the tissue damage of chronic bronchitis. As regards microbicidal activity of macrophages in patients with chronic bronchitis, no studies are available. Following pharmacological intervention, it is probably more reliable to measure specific components of macrophage metabolic and secretory activities, which are associated with microbicidal events, than to assess over-all microbicidal activity. PMID- 2239533 TI - Indices of inflammatory activity in CB and COAD. Phagocyte secretion and chemotaxis. AB - The monitoring of inflammatory activity in the lungs of patients with chronic obstructive airways disease may be accomplished by the measurement of specific markers of inflammatory cell activity such as the eosinophil cationic protein and the neutrophil-derived myeloperoxidase. However, no specific marker, which reflects the activity of the alveolar macrophage, is available. Eosinophil and neutrophil chemotactic activity may be detected in broncho-alveolar fluid as a sign of macrophage activity. We report preliminary data, which indicate that both chemotactic activities are elevated in patients with chronic bronchitis. The predominant activities elute at a molecular weight of about 10 kDa but also at a position after the total volume of the column. We conclude that secretory products from inflammatory cells may be measured in broncho-alveolar fluid from patients with chronic bronchitis. Whether such measurements will prove useful in relation to therapeutic trials in these patients is not known but is most likely. PMID- 2239534 TI - Inflammatory indices for chronic bronchitis and COAD. Proteases and antiproteases. AB - The study of lung secretion proteinases and their inhibitors, both functionally and quantitatively, provide information concerning the degree of inflammation in the lung. Interpretation of individual parameters may be difficult in isolation. However, a general pattern of response provides supportive evidence of a reduction in lung inflammation, including 1) reduction in plasma inhibitor concentrations, 2) increase in local inhibitor concentrations, 3) increase in enzyme inhibition, and 4) reduction in enzyme activity. Thus such changes provide an objective basis for the assessment of drug therapy. PMID- 2239535 TI - Exudative indices in airways inflammation. AB - Airways inflammation has come to be equated with the presence of inflammatory cells and their products in airway lumen and tissue. However, the inflammatory condition must also, or rather, be determined by indices which show to what degree the tissue itself is affected by the process. Plasma exudation from abundant subepithelial microvessels is a specific defence/inflammatory tissue response to mucosal provocations; promptly after extravasation, the plasma exudate reversibly and non-injuriously creates intercellular pathways across the mucosa; the exudate enters the airway lumen without compromising the epithelial lining as a barrier to luminal solutes; there is a good correlation between surface and tissue plasma exudates. I propose that plasma tracers on the mucosal surface can identify the ongoing airway inflammation, its intensity and time course in great detail. PMID- 2239536 TI - The measuring of "respiratory-membrane permeability" and local production of immunoglobulins and antibodies by means of an analysis of sputum. AB - When measuring the exudation of serum proteins and the local production of immunoglobulins and antibodies within the lung by means of an analysis of sputum, the permeability properties of the respiratory membrane should be taken into account. In this paper, we describe the "loss of size selectivity" that usually accompanies an increased permeability on the part of the respiratory membrane. This phenomenon enables us to measure respiratory membrane permeability independently of the sputum water content. Consequences with regard to discrimination between leakage from the circulation and/or local production of immunoglobulins and antibodies are discussed. Sequential studies which take these factors into account may provide insights into the extent of local inflammatory reactions in individual patients. PMID- 2239537 TI - A critical look at mucus markers. AB - Methods of collecting tracheobronchial secretions in conditions such as chronic bronchitis are reviewed. The virtual absence of such secretions in healthy lungs means that there is no normal baseline for comparison. In addition, the inaccuracy of most of the methods does not allow good quantitation of secretory output. A large number of physical and chemical analyses of secretions in many airways diseases does not point to any variables which are specific for the diagnosis of chronic bronchitis. This may be in part due to the contamination of glandular secretion by epithelial secretion, transudation and cellular debris. However, studies on mucus may be of value in following the course of disease and its response in therapy. PMID- 2239538 TI - Points of importance in long term intervention studies in CB/COAD. PMID- 2239539 TI - Which markers of inflammation should be used in therapeutic intervention studies of CB/COAD? PMID- 2239540 TI - The role of measurements of airway responsiveness. AB - In smokers with chronic airflow limitation (CAL), airway hyperresponsiveness (AHR) to stimuli like methacholine, which act directly on airway smooth muscle, are not specific for the pathogenesis which is responsible for AHR to methacholine in subjects with normal spirometry, nor predictive for a beneficial effect of glucocorticosteroid (GCS) treatment. In contrast, AHR to stimuli like hyperventilation, which act indirectly through mediator release, may be specific for the pathogenesis of asthma and predictive for a beneficial effect of GCS. The validation of this possibility requires the demonstration that patients with CAL and AHR to hyper-ventilation demonstrate improvement after treatment with GCS (and have an increase in eosinophils and metachromatic cells in the sputum or bronchoalveolar lavage (BAL), like that seen in asthmatics uncomplicated by CAL). PMID- 2239541 TI - Effects of corticosteroids in "chronic bronchitis" and "chronic obstructive airway disease". AB - In order to improve our knowledge concerning the supposedly beneficial effects of corticosteroids in patients with "chronic bronchitis" and "chronic obstructive airway disease" (COAD), it is necessary to define our patients carefully, so that every investigator can interpret the data adequately. Up to now, no definite conclusion can be drawn as to the profitable effect of corticosteroids in COAD. A combination of data from many studies on oral and inhaled corticosteroids strongly suggests that long-term studies in large groups of patients are essential if we wish to determine a potential treatment effect. In this way, a sub-group of patients who improve on corticosteroids may be found too. In addition to objective measurements, e.g. degree of airflow obstruction and airway hyperresponsiveness (AH), subjective data and information on the patient's quality of life and exacerbations should be included for evaluation. PMID- 2239542 TI - Epidemiology of obstruction, exacerbations and hyperreactivity. Effects of glucocorticosteroids and other anti-inflammatory treatment. AB - Validated and standardized questions are available for self-reporting of exacerbations of symptoms due to bronchopulmonary infections but not for non infective exacerbations. The presence of non-specific bronchial hyperresponsiveness may help to identify smokers with a high risk of rapid decline in lung function, but change in bronchial responsiveness with treatment probably cannot be used to predict subsequent long-term progression in FEV1. In non-asthmatic individuals three months' treatment with glucocorticosteroids has not improved FEV1 nor reduced bronchial responsiveness; the effects of glucocorticosteroids on bronchial secretions and infections and long-term decline in FEV1 are largely unknown. PMID- 2239543 TI - Airways hyperreactivity, bronchial inflammation and obstructive lung disease. AB - Understanding the mechanisms responsible for the development of chronic airflow obstruction is very important since this disease is the fifth leading cause of death in the United States and it produces a significant economic and social burden for society. Since reversal of established airflow obstruction is not possible, it would appear that the best prognosis and therapeutic results can be obtained by early diagnosis and prevention of irreversible disease. Understanding the underlying pathophysiologic mechanisms is necessary to detect susceptible individuals and develop effective interventions. PMID- 2239544 TI - Clinical trials in asthma and chronic airflow obstruction. AB - Clinical trials are becoming increasingly important in objectively evaluating therapeutic interventions in pulmonary medicine. Although the overall methodology for clinical trials is similar for most diseases, there are specific questions and problems unique to pulmonary medicine. This review is limited to a discussion of the general design and commonly encountered "problems and pitfalls" for clinical trials in respiratory medicine. Three examples of designs for intervention in asthma and chronic obstructive airways disease are presented. PMID- 2239545 TI - Inflammatory indices in chronic bronchitis. PMID- 2239546 TI - [Recent advances in the virological diagnosis of ocular disease]. PMID- 2239547 TI - [Optic nerve finding in experimental retinitis induced by herpes simplex virus]. AB - We reported histological changes and viral localization of HSV-1 in the optic nerve by the ABC-method and electron microscopy, after intravitreal inoculation. There was neither histological change nor antigen deposition on the specimen of 3 days after inoculation. Some series of antigen-positive sites were successively found along the nerve fiber from the lamina cribrosa to the optic chiasma in the optic nerve on 4 days after inoculation. Round cell infiltration were also found around these sites, and these changes increased on the 8th day. Antigen-positive cells were mainly considered to be oligodendroglia and astrocytes. These results suggested that HSV-1 infected the optic nerve fiber via the retina. On the way to be the brain by axonal transport, they would infiltrate to the glial cells, where they could replicate and spread to neighbouring glial cells. PMID- 2239548 TI - [Chronic organophosphorus intoxication and aging in rats]. AB - Possible acceleration of aging due to the administration of organophosphorus pesticide (OP) was studied. Fenthion (6 mg/kg/day) was subcutaneously administered dorsally to rats over a period of 12 weeks. The amounts of fluorescent lipid peroxidation products (FLPP) and superoxide dismutase (SOD) activity were measured in various tissues. Microscopic examination was added only in the lens. The amount of FLPP in the retina-choroid, lens, kidney and heart of the rats was found to be increased (lens; p less than 0.01, kidney; p less than 0.05). The activity of SOD in the retina-choroid, optic nerve, liver and heart increased temporarily, but eventually returned to control levels. The lens preparations at the end of the 12-week administration period showed irregular bow configuration and epithelial nuclear dislocation in the bow area. FLPP are fluorescent products produced by peroxide lipids and their amounts increase with aging. Increase in the amounts of these products and microscopic findings for the lens were indications of the progress of aging. There is thus the possibility that the inducement of SOD production may decrease with aging. It was concluded that the organophosphorus pesticide may accelerate the aging of rats. PMID- 2239549 TI - [Rapid etiologic diagnosis of epidemic keratoconjunctivitis]. AB - We evaluated enzyme-linked immunosorbent assay (Adenoclone) in 253 cases of epidemic keratoconjunctivitis (EKC), pharyngeal conjunctival fever (PCF) and acute conjunctivitis. The clinical diagnosis due to adenoviral ocular infection was 86/114 (75%) in EKC, 26/50 (52%) in PCF and 25/89 (28%) in acute conjunctivitis, Adenoclone was positive only within 7 days after the disease onset. The specificity (87%) and sensitivity (74%) of Adenoclone were confirmed by isolate cell culture. Cases with corneal complication due to adenoviral infection show higher a value than the OD value in Adenoclone and the bulbar conjunctiva is a suitable site to detect adenoviral antigen. In this survey, isolated adnovirus type 4 was recognized in 53%, Ad8 in 14%, Ad3 in 13%, Ad37 in 5%, Ad19 in 2% and non typed Ad in 12%. Clinical findings due to Ad4 showed EKC in 50%, PCF in 30% and acute conjunctivitis in 20% respectively. PMID- 2239550 TI - [Clinical features of uveitis in childhood during the past 20 years]. AB - One hundred and fifty five cases (237 eyes) of children with uveitis were clinically observed in the past 20 years. There was no fluctuation in the number of patients during the period. Concerning the age as the first visit, the smallest group was under 4 years of age and the numbers of patients increased at ages 14 and 15. Chief complaints usually corresponded to the age of the cases. Cases with anterior uveitis accounted for 25% of all cases, intermediate uveitis 12%, posterior uveitis 45% and panuveitis consisted of 17% of all cases, respectively. In the course of treatment, improvement of visual acuity was not statistically significant; the visual prognosis of cases affected under age 7 years was relatively poor. At the time of final observation, the visual acuity of cases, who had first visited during the past 10 years, were better than those who presented during the previous decade. Uveitis had healed or improved in 68% of cases treated in our clinic. As complications, band-shaped keratopathy was seen in 8% of the patients, cataract in 22% and glaucoma in 5%, respectively. Thirty two per cent of the cases received systemic steroid therapy and the average duration was 3.8 months. Fifty two operations were performed in 30 cases (19%), 37 eyes (16%); 16 were cataract operations and 24 were operations for glaucoma. PMID- 2239551 TI - [Retinochoroidal changes in toxemia of pregnancy with the relation to hypertensive retinopathy and choroidopathy]. AB - Thirty patients who suffered from ocular involvement caused by toxemia of pregnancy were examined ophthalmologically during the nine-year period between 1980 and 1988 at Osaka Medical Center and Research Institute for Maternal and Child Health. The ophthalmoscopic findings were divided into the following five categories: cotton wool patches (CWP), retinal hemorrhages (RH), hard exudates (HE), yellowish opaque foci (YOF) and serous retinal detachments (SRD). Although the first three types of findings were recognized as hypertensive retinopathy (Keith-Wagener III or IV), the last two were recognized as choroidal vascular damage. Based on the frequency of fundus findings, patients were divided into three types: R-type mainly suffered from retinal vascular occlusion (CWP), C-type mainly suffered from choroidal vascular occlusion (YOF, SRD), and R + C-type consisted of mixed vascular occlusion. The maximum systolic blood pressure of C type patients was significantly lower than that of R-type. The maximum diastolic blood pressure of C-type patients was also significantly lower than those of R type and R + C-type. There were five C-type cases with systolic blood pressure of less than 160 mmHg in which the choroidal ischemia was concluded not to be hypertensive choroidopathy but a specific alteration characterized by toxemia of pregnancy (hypercoagulopathy). PMID- 2239552 TI - [Treatment and prognosis of retinoblastoma from 1975 to 1987]. AB - Among 21 cases of retinoblastoma (28 eyes) treated during the past 14 years in our clinic, 14 cases were unilateral, and 7 were bilateral. The average ages at the first visit were 27 months in unilateral cases and 7.2 months in bilateral cases. In all unilateral cases, in all of which the tumors were large (over group III according to Reese's classification), we removed the affected eye, and all patients survived without any evidence of metastasis or recurrence during a 5 year follow-up period. In bilateral cases, we removed the advanced eyes in which the tumors were large (over group III according to Reese's classification) in all cases, and the contralateral eyes underwent conservative treatment by radiotherapy, photocoagulation or chemotherapy. When tumors in contralateral eyes were small (Group I or II in Reese's classification), tumors of the retina subsided and all patients survived without recurrence or metastasis. However, when the tumors were large (group V), tumors of retina did not subside and survival was very poor. Our results show that the prognosis for survival in bilateral cases depends mainly upon the size of the tumor in the remaining eye. PMID- 2239553 TI - [Interferon-alpha for the treatment of retinal vasculitis associated with human T lymphotropic virus type I myelopathy (HAM)]. AB - Interferon-alpha was effective for the treatment of retinal vasculitis and vitreous opacity in a patient with human T-lymphotropic virus type I associated myelopathy (HAM). The patient was a 40-year-old male with retinal vasculitis, vitreous opacity and Koeppe's iris nodules. Systemic administration of corticosteroid hormone was not fully effective for the treatment of ocular involvements except for iris nodules. After Interferon-alpha treatment, given 3 million IU/day as the intramuscular injection for 4 weeks, the retinal vasculitis subsided and vitreous opacity disappeared. PMID- 2239554 TI - [Clinical study of risk factors concerning arteriosclerosis of the patients undergoing hemodialysis]. AB - To study the risk factors of arteriosclerosis of the patients undergoing hemodialysis, aortic pulse wave velocity (PWV) was measured in 42 patients (26 male and 16 female) undergoing hemodialysis. The relationships were examined between PWV value and various risk factors, such as age, blood pressure, serum lipid level and aortic calcification index (ACI). PWV value was elevated with age and it was higher in the patients group than the age-matched control subjects. There was a statistically significant correlation between PWV value and blood pressure. The effect of elastase on PWV value was found in the patients with high PWV value (over 9.0 m/sec). However, no correlations were found between PWV value and serum lipid level such as total cholesterol, triglyceride, HDL-cholesterol and beta-lipoprotein. On the other hand, PWV value was changeable according to ACI and this relationship was statistically significant (p less than 0.01). These results suggested that aortic calcification could be one risk factor for arteriosclerosis of the patients with chronic renal failure undergoing hemodialysis. PMID- 2239555 TI - A clinical study of total cystectomy for transitional cell carcinoma of the urinary bladder. AB - Fifty six patients with transitional cell carcinoma of the urinary bladder were treated by total cystectomy from January, 1979 through December, 1988. A retrospective study was conducted on 52 patients on whom prognosis could be followed up. There were 40 men and 12 women (male to female ratio: 3.3: 1), between 32 and 79 years old (mean age, 64.1 years old). The overall 1-, 3- and 5 year survival rates were 65.8%, 54.1% and 43.0%, respectively. The 5-year survival rates for patients with low grade (G, I, II) and high grade (G. III) were 41.9% and 42.7%, respectively: with no significant difference in the survival curves between the two groups. The 5-year survival rates according to histopathological stage were 78.9% for patients in low stage, 24.7% in high stage, and the difference in the survival curves between the two groups was statistically significant (P less than 0.001). The mortality in the 21 cases of the 33 high stage cases in which cisplatin was used was 42.9%, with 3- and 5-year survival rates were 53.1% and 36.8%, respectively. In the remaining 12 cases in which cisplatin was not used for post-operative chemotherapy, the mortality in the 12 cases was 83.3%, with 3- and 5-year survival rates of 25.1% and 12.3%, respectively. Thus, the patients who received post-operative chemotherapy showed a better survival rate than those who did not with a significant difference (P less than 0.05). The results of the present study suggest the usefulness of post operative adjuvant chemotherapy in the high stage case. PMID- 2239556 TI - [Ultrasonographic assessment of intravesical urine volume]. AB - The assessment of intravesical urine volume is very important in the management of the patients with lower urinary tract obstruction or incontinence. As the non invasive method for measuring residual urine volume, accuracy and usefulness of ultrasonographic measurement was evaluated in a total of 116 occasions in comparison with the conventional catheter technique. The values of the maximum transverse (W), cranio-caudal (H) and antero-posterior distance (D) of the inflated bladder were obtained by trans-abdominal scanning. These parameters were used for the ellipsoid formula (pi/6 x W x H x D). The ultrasonographic measurement of urine volume showed a high coefficiency against the conventional catheterized volume (r = 0.9543). Although a mean standard error was 56.3% of the actual volume, the amount of residual urine at the target of 50 ml and 100 ml could be accurately assessed by ultrasound with an accuracy of 90.5%. The method was also valid in follow-up study to monitor the changes of residual urine volume. The ultrasonographic assessment of intravesical urine volume is, thus, a non-invasive, useful tool in the management of the patients with voiding disturbance. PMID- 2239557 TI - [The effect of ganglioside on diabetic neurogenic bladder]. AB - The effect of ganglioside was studied in 6 diabetic patients with neurogenic bladder. Ganglioside is glycosphingolipids which seems to be involved in the processes of nerve growth, regeneration and tissue reinnervation. The treatment consisted in the daily intramuscular administration of 20 mg ganglioside. Clinical symptoms, vibration sensation and urodynamic studies were recorded at the beginning and 4 weeks later. The clinical responses assessed by subjective complaints and vibration sensation were effective, but no statistically significant difference in urodynamic studies was obtained. Side effects were not observed. In conclusion, ganglioside treatment seems to have a positive effect on diabetic neurogenic bladder. PMID- 2239558 TI - [A case of retroperitoneal tumor presenting with gross hematuria]. AB - A case of retroperitoneal tumor presenting with gross hematuria is reported. A 62 year-old female consulted our clinic with the chief complaint of gross hematuria. On physical examination, a goose-egg sized tumor was palpable in the left flank region. Drip infusion pyelography and computerized tomographic scan showed left retroperitoneal tumor which deviated the left kidney upwards. Percutaneous needle biopsy of the tumor revealed no malignancy. Total resection of the tumor was performed subsequently. A yellowish solid tumor was macroscopically encapsulated by fibrous tissue, weighed 230 g and 6 x 7 x 10 cm. Histopathological diagnosis was malignant schwannoma. After operation, the hematuria stopped without any treatment and deviation of the left kidney was improved. Soft tissue tumor should be treated by adjuvant chemotherapy with irradiation because of its high frequency of recurrence and metastasis. Combined chemotherapy with VCR, ADR, CPM and DTIC (CYVADIC) was performed and she is in good health at 1 year after operation. PMID- 2239559 TI - Solitary pancreatic metastasis from renal cell carcinoma. AB - A case of asynchronous bilateral renal cell carcinoma with pancreatic metastasis is described. Left nephrectomy and tumorectomy in the right kidney were performed. Solitary metastasis to the pancreas without symptoms was treated by distal pancreatectomy with tumor and splenectomy. Although bilateral renal cell carcinomas were histologically renal cell carcinoma (clear cell subtype, grade 2), the resected pancreatic tumor was renal cell carcinoma with sarcomatoid change. Therefore, the metastatic tumor had a more malignant potential than the primary tumor. The pancreatic metastasis was seen at 6 years 10 months and 2 years 6 months after left nephrectomy and enucleation of the right renal tumors, respectively. The patient is alive without disease and is being treated by alpha interferon for 12 months after distal pancreatectomy. A careful long-term follow up of the patient with renal cell carcinoma seems to be necessary. PMID- 2239560 TI - [Danazol therapy of endometriosis of the bladder and ureter: a case report]. AB - Endometriosis of the urinary tract is uncommon. A thirty-year-old woman was referred to our hospital, complaining of macrohematuria. Intravenous pyelography (IVP) showed bilateral hydro nephrosis. Cystoscopic examination revealed a mass around the bilateral ureteral orifice. Danazol therapy was commenced. After 6 months of therapy, IVP showed the improvement of hydronephrosis of left kidney and cystoscopy revealed the resolution of most of the mass in the bladder. For definite diagnosis and treatment, danazol therapy is considered to be effective for endometriosis, but if secondary fibrosis has occurred, surgical treatment may be necessary. PMID- 2239561 TI - [A case of everting ectopic ureterocele in child--controversy in the surgical treatment]. AB - A 4-year-old girl with the history of repeated urinary tract infections was referred from the pediatric department to our department on January, 1987. Under the diagnosis of right ectopic ureterocele of everting type with complete duplication of renal unit, the one-stage operation, that is, right hemi nephroureterectomy with complete excision of the ureterocele and ureteral stump was carried out on January 27, 1987. Reimplantation of the orthotopic mate ureter was done because of injury to lower part of the mate ureter during operation, although reflux of the mate ureter did not exist. After the operation, the voiding symptom became better except for large residual urine volume (300 ml). In order to protect renal function, intermittent catheterization was carried out. Two years and 8 months after that operation, residual urine volume was reduced to 20 ml. Judging from the literature and our experience, if the patient is not in a severe condition, we recommend one-stage operation, that is, total correction (a single operation designed to correct abnormalities of the upper and lower urinary tract) for ectopic ureterocele in children. PMID- 2239562 TI - [Primary paraganglioma of the urinary bladder: a report of two cases]. AB - We report two cases of primary paraganglioma of the urinary bladder. Case 1. A 61 year-old man was hospitalized with the chief complaints of gross hematuria, dysuria and headache. The patient had a history of hypertension. Cystoscopy disclosed a nonpapillary, sessile tumor in the retrotrigonum of the bladder. An attack of paroxysmal hypertension was induced by bimanual palpation of the tumor, and paraganglioma was suspected. Partial cystectomy with staging pelvic lymphadenectomy was performed. Case 2. A 65-year-old man was hospitalized with the chief complaints of gross hematuria and urinary retention. The patient had no history of hypertension. Cystoscopy disclosed a nonpapillary tumor in the right lateral wall of the bladder. Transurethral resection was performed with no cardiovascular complication. Prostatic needle biopsy showed the histological evidence of prostatic adenocarcinoma. Radical retropubic prostatectomy with limited lymphadenectomy was performed. There was no histological evidence of lymph node involvement of paraganglioma or adenocarcinoma. The histological and biochemical examinations revealed a chromaffin positive, functioning and non malignant tumor in Case 1, and a chromaffin negative, non-functioning and non malignant tumor in Case 2. In total, 29 cases of primary paraganglioma of the urinary bladder have been so far reported in Japan. The tumor recurrence, multiple or metastases were recorded in 8 of 29 cases (27.6%), mainly in regional lymph node metastases. We recommend lymphadenectomy at the initial operation, irrespective of pathological finding of the primary paraganglioma of the urinary bladder. PMID- 2239563 TI - [Primary malignant lymphoma of the urinary bladder: report of a case]. AB - A case of primary malignant lymphoma of the bladder is presented. A 42-year-old woman was admitted to our clinic with the chief complaint of asymptomatic hematuria. Examination of cystoscopy, IVP, ultrasonography and CT scan suggested a non-epithelial tumor of the bladder, which was reported as malignant lymphoma, non-Hodgkin, by findings of transurethral biopsy. Subsequent systemic CT scan, Ga scintigraphy and bone marrow puncture revealed no abnormalities. Therefore, this case was thought to be primary malignant lymphoma of the bladder. Partial cystectomy with pelvic lymph node resection was carried out. The tumor, 2 x 1 cm in diameter, invaded into the middle portion of muscularis. Histological diagnosis of the tumor was follicular lymphoma, medium-sized cell type according to LSG classification, and immunohistological findings also showed B-cell lymphoma. Resected lymph nodes had no signs of neoplasms. Postoperative adjuvant chemotherapy consisting of vincristine, cyclophosphamide and prednisolone was performed. She has been doing well without any clinical evidence of recurrence for 16 months after the operation. PMID- 2239564 TI - [A bulky mass non-Hodgkin's lymphoma with dysuria in the rectovesical space]. AB - A case of non-Hodgkin's lymphoma is reported. A 71-year-old man presented with complaint of dysuria and urinary frequency. Rectal examination and CT scan revealed a bulky mass in the rectovesical space. Transperineal needle biopsy of the tumor revealed non-Hodgkin's lymphoma, large cell type, diffuse. The patient received combination chemotherapy of adriamycin, cyclophosphamide, vincristine, prednisolone and pepleomycin. After two days the tumor was marvelously reduced in size, and partial response (PR) by CT was achieved after two months. PR was sustained for two months with cyclophosphamide, vincristine and prednisolone. However, the tumor progressed gradually, and he died five months after the first treatment and two additional courses of chemotherapy. Autopsy showed a 1,700 g bulky mass in the rectovesical space. The mass was covered with peritoneum and had a fistula from rectum to central necrosis of the tumor. Nine cases of the non Hodgkin's lymphoma with complaint of dysuria have been reported in Japan before our case, which seemed to arise from the submucosal tissue of anterior rectal wall, prostate or lymphatic tissue of rectovesical space. PMID- 2239565 TI - Leiomyoma of the bladder causing bilateral hydronephrosis: a case report. AB - We report a case of bladder leiomyoma with marked bilateral hydronephrosis caused by chronic urinary retention. Surgical finding was that the mass was smooth, fist sized and had a thin stalk connected to the bladder wall. The tumor was completely removed. Histopathological diagnosis was leiomyoma of the bladder and the post-operative course was uneventful. PMID- 2239566 TI - [A case of urachal abscess]. AB - A 26-year-old male with urachal abscess was demonstrated. Ultrasonography, CT and MRI revealed that there was a mass at the supravesical region, which was connected to the umbilicus. However, a differential diagnosis as to whether the mass was a tumor or an abscess was difficult from these examinations. Thus we performed an open biopsy. A pathological examination revealed no malignant change in the biopsy specimen. On the other hand, the pathological diagnosis of a follicular tumor located at the roof of the urinary bladder was TCC G2, but we considered that, this change was a reactive hyperplasia with dysplasia resulting from chronic inflammation of urachal abscess. Thus, the complete excision of urachal abscess and partial cystectomy were performed. The serial sections of the bladder wall revealed no malignant changes. We reviewed similar cases reported in our country and discussed various factors causing urachal abscess, especially related to the infectious root. PMID- 2239567 TI - [Two cases of benign polyps of the posterior urethra (ectopic prostatic tissue)]. AB - We report two cases of benign polyps of the posterior urethra. Their first symptoms were gross hematuria and urinary frequency. Both specimens obtained by transurethral resection were histologically identified as prostatic tissue. Discussion on benign polyps of the posterior urethra as ectopic prostatic tissue was done with review of literature. PMID- 2239568 TI - [Utility of pre-operative imaging diagnosis in spermatic cord liposarcoma]. AB - A case of spermatic cord liposarcoma was revealed by imaging diagnosis. The patient was a 59-year-old male, who consulted our clinic with the complaint of painless right scrotal swelling on June 30, 1989. One year earlier, he noticed this swelling, which was slow growing little by little. Palpation revealed a movable mass in right scrotum, 7 x 3 x 3 cm in size and separated from the right testis. Scintigraphy could not show RI accumulation and ultrasonography showed a capsulated homogeneous mass. Computed tomography (CT) and magnetic resonance imaging (MRI) showed capsulated fat-like almost homogeneous mass, which enclosed the right spermatic cord. This mass was suspected of spermatic cord lipoma or liposarcoma and was removed with radical orchiectomy. The weight of the mass was 246 g. This mass had a bunch of grape appearance and consisted of several masses of various sizes surrounding the spermatic cord, and could be separated from the right epididymis and testis. Histological examination revealed well differentiated liposarcoma and lipoma. Spermatic cord liposarcoma is very rare and this preoperative diagnosis is very difficult. Imaging diagnosis, such as CT, MRI may help our preoperative diagnosis. PMID- 2239569 TI - [Clinical evaluation of ofloxacin in the treatment of chronic complicated urinary tract infection]. AB - Ofloxacin was administered orally at a daily dosage of 300 mg and 600 mg in three divided doses for 14 days to 24 and 60 patients with chronic complicated urinary infections, respectively, in order to evaluate the therapeutic efficacy. The clinical efficacy was evaluated according to the criterion proposed by the UTI Committee in Japan and its efficacy was evaluated in 84 cases. In the group of 24 patients receiving a daily dosage of 300 mg, the clinical effectiveness after a 5 day treatment was excellent in 13 cases and moderate in 7 cases. The overall clinical efficacy was 83.8%. In the group of 60 patients receiving a daily dosage of 600 mg, the rate of overall clinical efficacy after a 5-day treatment was 83.3%, being excellent in 23 cases and moderate in 27 cases. The eradication rate was 85.3% and 92.5% by 300 mg and 600 mg dosages of ofloxacin, respectively. As adverse reactions, anorexia and nausea occurred in 2 cases. Laboratory anomalies consisted of 1 case of slight and transient elevation of transaminase, and 1 case of elevated serum creatinine. PMID- 2239571 TI - [Comparison of the effects of various immunosuppressive drugs on subrenal capsule assay (SRC assay)]. AB - We evaluated the effect of various immunosuppressive drugs in the SRC assay. We chose the most appropriate day to obtain the results of the SRC assay using the MBT-2 tumor. MBT-2 tumor-bearing mice of homogenic and heterogenic strains were separately given one of the three: cyclophosphamide, azathioprine or mizoribine. These drugs were evaluated on the 6th and the 11th day for the immunosuppressive effects expected from a host versus graft reaction. Concerning the homogenic mice that were injected with drugs, on the 11th day, the growth of the tumor was favorably suppressed in comparison with the growth of the control group (A-1) due to the anti-tumor effect of immunosuppressive drugs. We concluded that the 6th day was the most, appropriate day to obtain the results of this assay. Concerning the heterogenic mice, similar results were observed. In the mizoribine-group, we subcutaneously injected 200 mg/kg on alternate days. Yet the implanted tumor grew almost at the same rate as that of the A-1 group. In this group, a histological study showed reduction of the tumor cells and few inflammatory cells. We concluded that this drug was more useful than the others in the SRC assay and the suitable day for judgement was the 6th day. PMID- 2239570 TI - [Clinical evaluation of the combination of carumonam and fosfomycin in the treatment of complicated urinary tract infection]. AB - Carumonam (CRMN), the first monobactam antibiotic in Japan, has excellent activity against gram-negative bacteria and is useful in the treatment of urinary tract infections. However, it may be insufficient in the treatment of complicated urinary tract infections because of the increase in isolation of gram-positive bacteria, and it may be necessary to co-administer antibiotics active against gram-positive organisms to achieve a broader spectrum of coverage in connection with severe infections. The combination of CRMN and fosfomycin (FOM) was evaluated for its effectiveness and safety at the Department of Urology, Yamagata University Hospital and 7 affiliated hospitals. Clinical efficacy was assessed on 64 patients with complicated urinary tract infection according to the Criteria for Clinical Evaluation of Antimicrobial Agents in UTI (3rd. ed.) recommended by the Japan UTI Committee. Clinical efficacy was evaluated as excellent in 16, moderate in 32, poor in 16, with an overall clinical effectiveness rate of 75.0%, which is superior compared with CRMN alone. Of the total of 92 bacterial strains isolated, 66 (71.7%) were eradicated. Subjective adverse reaction was seen in 1 patient (1.4%), as nausea and anorexia. Slight increases in serum GOT and GPT ware recorded in 5 patients (7.1%). These findings disappeared after the termination of administration without treatment. The combination of CRMN and FOM might therefore be useful in the treatment of complicated urinary tract infections. PMID- 2239572 TI - [Subrenal capsule assay for chemosensitivity test of urological malignancy]. AB - We evaluated the subrenal capsule assay with a chemosensitivity test using 47 fresh surgical explants, including 16 renal cell carcinomas and 10 uroepithelial cancers. Forty-one explants were evaluable and 166 drug tests were performed. Forty-seven tests (28.3%) were found to be sensitive. Ten of 16 renal cell carcinomas involved a sensitive drug, 3 involved more than 2 sensitive drugs. VP 16, ADM, BLM and 5-FU were the most sensitive compared with the others. Concerning the uroepithelial cancers, 8 of 10 involved a sensitive drug, 5 involved more than 2 sensitive drugs. CDDP and VP-16 were more effective than the other drugs. This result showed a good correlation with the clinical therapeutic efficacy using CDDP. In the future, we hope to evaluate the clinical correlation between clinical efficacy and this assay. PMID- 2239573 TI - [Treatment using CDDP and radiation therapy in treating bladder tumor]. AB - Combination therapy consisting of cis-diamine-dichloroplatinum (CDDP) and radiotherapy was used to treat bladder cancer. The subjects were 20 patients with bladder cancer we experienced since September, 1986. They were between 33 and 83 years old and consisted of 13 males and 7 females. Among the histotypes and grades, there were 3 cases of G2, 7 of G2-G3 and 10 of G3 metastatic epithelial carcinoma. The classification of primary tumors was T2 in six cases, T3a in 12 cases and T4 in two cases. In 12 cases where the bladder was preserved, this therapy was performed after TUR biopsy or TUR, and the effects were evaluated after observation periods of 5-17 months. Side effects caused by CDDP were anorexia in 15 cases, nausea and vomiting in 10 cases, leukopenia in 10 cases and thrombocytopenia in four cases. Those caused by the radiotherapy were diarrhea in seven cases and skin disorders in six cases. All of these side effects were mild and the patients recovered spontaneously. PMID- 2239574 TI - [Neurogenic bladder after operation of rectal cancer]. AB - Of the patients who had had a urodynamic examination during the five year period from 1982 to 1987 in our clinic, 48 patients underwent operations for rectal cancer prior to the study. In 35 of them, the operation mode was known. If the pelvic nerve is damaged by operative modes for rectal cancer, urinary disturbances of severe kinds may occur. In spite of such disturbances, 71.4% of those who had had excision of the low anterior part and 51.9% of those with Miles' operation could be weaned from the clean intermittent self-catheterization and take up spontaneous urination. Even in patients who developed severe dysuria, if catheterized at an early stage, many of them could urinate by abdominal pressure with in several months after operation, without the aid of a catheter. This transition took place mostly within one year after operation. When a patient develops dysuria after radical surgery for rectum cancer, treatment mainly with self-catheterization is an effective method at present. PMID- 2239575 TI - [Study on etoposide therapy of relapsing prostatic cancer patients]. AB - Eight patients with hormone resistant prostate cancer were treated with 30 mg/m2 etoposide every two or three weeks. A response rate of 37.5% in clinical status was noted. Slight toxicity was seen temporarily. We think this etoposide therapy is a useful regimen for advanced or relapsing carcinoma of the prostate. PMID- 2239576 TI - [Effect of tegafur administration combined with hormonal therapy in patients with newly diagnosed stage D prostatic cancer]. AB - To study the effect of tegafur administration combined with hormonal therapy on the survival rate of newly diagnosed patients with stage D prostatic cancer, 66 patients, 70.9 years old in mean age, were treated from 1979 to 1986. The cancer was proven by the histological or cytological examination of the specimen which was obtained by the needle biopsy and/or aspiration biopsy of the prostate. The histopathological diagnosis of 59 patients was as follows: well differentiated type of adenocarcinoma was observed in 13 patients, moderately differentiated type in 19 cases, poorly differentiated type in 24 cases and mixed type in 3 cases. Daily 600 mg tegafur was administered orally as long as possible from the beginning of the treatment combined with hormonal therapy. Actual and relative 5 year survival rates calculated with Kaplan-Meier's method were 31.2% and 39.2%, respectively. When deaths other than prostatic cancer death were counted as lost cases, the actual survival rate was 47.5%. The present study also demonstrated that there were some factors affecting the patients' prognosis. They were the age of onset of the disease (patients under 64 years old were worse than those over 65 years old; p less than 0.05), performance status (patients with PS from 0 to 2 at the first admission were better than those with PS 3 to 4; p less than 0.025), differentiation of the tumor (well differentiated type was better than moderately; p less than 0.025 or poorly differentiated type; p less than 0.005). PMID- 2239577 TI - [Clinical studies on chronic prostatitis and prostatitis-like syndrome (4). The kampo treatment for intractable prostatitis]. AB - Kampo treatment was attempted in cases of chronic nonbacterial prostatitis and prostatitis-like syndrome which was intractable or recurred when treated with western medicine. The clinical effects of Kampo treatment were excellent in 21.3% with an efficacy rate of 67.2% for the cases with chronic non-bacterial prostatitis, and excellent in 19.5% with an efficacy rate of 52.4% in the cases with prostatitis-like syndrome. When the clinical effects were compared with those of western therapy performed in the cases which had recurrence, Kampo treatment showed more excellent effects (p less than 0.1) for both types of disease, and the treatment with Chinese medicine was suggested useful. In a comparison of the effects between the cases given only Kampo treatment and those given both Kampo treatment and western treatment using anti-inflammatory agents, no difference was seen in the cases with the prostatitis-like syndrome, but in the cases with chronic non-bacterial prostatitis, the effects were better in the concomitant treatment group than in the group given only Kampo treatment (p less than 0.1). The response to the Kampo treatment differed depending on the type of disease. Among the antibacterial agents used concomitantly in the cases of chronic non-bacterial prostatitis, new-quinolones showed better results than ST compounds or tetracyclines, but no statistically significant differences were seen among the drugs. Of the Kampo drugs used, Keisibukuryogan and Simotuto showed high clinical usefulness in both types of disease and there was no statistically significant difference among the other drugs. The incidence rate of side effects (Goji) due to Kampo treatment was 6.3% and was higher in patients administered Keisibukuryogan. PMID- 2239578 TI - [Malignant pheochromocytoma presenting as an acute abdomen: a case report]. AB - A case of right adrenal malignant pheochromocytoma was reported. The patient was a 16-year-old boy who complained of severe right side abdominal pain due to spontaneous hemorrhage into the retroperitoneal space. Right adrenalectomy was performed on Feb. 22, 1988 but the preoperative high serous catecholamine level did not drop to the normal level. Postoperatively bone and liver metastasis were detected by a 131I-MIBG scan. He was treated with a combination chemotherapeutic regimen consisting of cyclophosphamide, vincristine and dacarbazine in 2 repeated cycles but there was no effect. He died 5 months after the operation. PMID- 2239579 TI - [A case of primary aldosteronism due to unilateral multiple adrenal adenomas]. AB - A 64-year-old female with hypertension, hypokalemia visited our hospital. Endocrinological examinations showed a low level of plasma renin activity and high level of plasma aldosterone. Circadian rhythmicity of plasma aldosterone level was recognized. No change in the plasma level of aldosterone was observed after loading of standing and administration of furosemide. Adrenal scintigraphy, adrenal venous aldosterone assay and CT scan revealed two tumors in the left adrenal. The diagnosis of primary aldosteronism by left adrenal tumors was made from the above findings. A left adrenalectomy was performed and pathological findings showed two adenomas, which had no capsule either and were surrounded by normal adrenocortical tissue. Blood pressure normalized after surgery and the plasma levels of aldosterone and plasma renin activity were normalized. PMID- 2239580 TI - [A case of renal cell carcinoma and bladder carcinoma associated with von Hippel Lindau disease]. AB - A case of renal cell carcinoma and bladder carcinoma associated with von Hippel Lindau disease is reported. A 31-year-old female was referred to the Department of Urology for further examination of right renal mass which was incidentally found on abdominal computed tomography (CT). The patient was operated on spinal hemangioma in May 19 and July 8, 1975, on cerebellar hemangioblastoma in July, 1976 and June 10, 1981 and on cerebellar cyst in June 20, 1988. Angiography revealed three hypervascular renal tumors in the right kidney. Cystoscopy revealed a papillary bladder tumor (TCC Grade 1). Transurethral resection of bladder carcinoma was performed on July 28, 1988. Right radical nephrectomy and lymphadenectomy were performed on August 2, 1988. Histopathologically, the tumor was renal cell carcinoma of clear cell type (Grade 1). Postoperative course was uneventful and the residual kidney is being followed up in the outpatient clinic. PMID- 2239581 TI - Metastatic tumor of the spermatic cord from renal cell carcinoma. AB - A 56-year-old male visited our hospital with macroscopic hematuria. Physical and X-ray examinations showed he had right renal cell carcinoma with tumor thrombosis in the inferior vena cava and the right spermatic vein. Radical nephrectomy and tumor thrombectomy were performed and he was discharged with no evidence of disease 1 month after the operation. At 5 months after the discharge, he noticed a palpable mass in the scrotum. Right orchiectomy was performed. The tumor was located in the right spermatic cord and histological examination revealed it to be a renal cell carcinoma (clear cell subtype) which was a metastatic lesion from a right renal tumor. In this case, the renal cell carcinoma was considered to have retrogradely metastasized through the spermatic vein. In conclusion, a complete physical examination, including the spermatic cord is recommended during the follow-up period of renal cell carcinoma. PMID- 2239583 TI - Giant renal angiomyolipoma with an uncommon growth pattern: a case report. AB - A case of a giant renal angiomyolipoma with uncommon growth pattern in a 66-year old female is reported. The tumor originated from the upper pole of the left kidney and simultaneously grew posteriorly in a sheet-like fashion while a spheroid mass projected upwards. With magnetic resonance imaging (MRI), the relationship between the tumor and adjacent organs was clear. Tumorectomy employing cavitron ultrasonic surgical aspirator (CUSA) was performed, and proved to be a safe and simple procedure. There has been no recurrence of the growth 2 years post-operatively. PMID- 2239582 TI - [A case of double cancer: renal cell carcinoma and transitional cell carcinoma of urinary bladder]. AB - This is a case report on a patient with double cancer of kidney and urinary bladder. The patient was a 65-year-old female, and she was admitted with the chief complaint of gross hematuria and right flank pain. After careful examinations, she was diagnosed with right nonfunctioning kidney caused by invasive bladder cancer. Computerized tomography incidentally revealed a mass in the upper pole of the left kidney. Selective left renal arteriography showed stretched arteries and irregularity and tortuosity of the smaller vessels. She was diagnosed with double cancer of bladder and left kidney. Owing to the damage of the right renal function, left partial nephrectomy, total cystectomy, right nephroureterectomy and left ureterocutaneostomy were performed. According to DMSA scintigraphy measured 15 days later, the uptake value of the left kidney was 13.25%, compared to the preoperative value of 25.62%. To date, this case is 36th reported case in Japan. PMID- 2239584 TI - A case of adenocarcinoma of the renal pelvis. AB - A 28-year-old female had adenocarcinoma arising from the renal pelvis with ascites containing adenocarcinoma cells. The primary site was treated with radical nephrectomy, resection of the remnant ureter with a bladder cuff. Combination chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (CAP) was performed as an adjuvant therapy. Approximately 3 years after the nephrectomy, she is currently alive with no clinical evidence of recurrence. CAP seems to have been effective in the treatment of the disease. PMID- 2239585 TI - [Transitional cell carcinoma of the renal pelvis in a woman discovered at childbirth]. AB - We report a case of transitional cell carcinoma of a renal pelvis in a woman discovered after childbirth. A 38-year-old woman, who delivered an immature male infant in cesarean section 29 days prior to hospitalization, was admitted complaining of asymptomatic gross hematuria. Excretory urography and retrograde pyelography showed a filling defect of the right renal pelvis, Spontaneous urine cytology indicated class 5. Renal computed tomographic scan demonstrated a mass lesion in the right kidney. Right total nephroureterectomy and partial cystectomy was performed for diagnosis and treatment. Pathological diagnosis was papillary transitional cell carcinoma (grade 2). This is the first case of transitional cell carcinoma of the renal pelvis occurring in a childbearing woman in Japan. PMID- 2239586 TI - [Clinical evaluation of sultamicillin in the treatment of urinary tract infections]. AB - Sultamicillin, a new semisynthetic oral beta-lactam antibiotic, was evaluated for its antibacteria susceptibility and clinical efficacy against urinary tract infection (UTI), and the following results were obtained. The sensitivity of sultamicillin (SBTPC) on 518 strains of clinical isolates from the urine were tested and compared to ampicillin (ABPC). S. aureus, S. epidermidis, Enterococcus sp., Streptococcus sp., E. coli, K. pneumoniae, K. oxytoca, P. mirabilis, M. morganii and Acinetobacter sp. showed high sensitivity to SBTPC. The antibacterial activity of SBTPC was superior to that of ABPC in most strains and especially more superior in beta-lactamase producing strains. The clinical effectiveness rate on a total of 15 patients with acute uncomplicated cystitis was 93.3% and the eradication rate of causative organisms was 93.3%. On 15 patients with chronic complicated UTI, the clinical effectiveness rate was 73.3% and eradication rate was 76.5%. Side effects (diarrhea) were observed in 3 cases, but this symptom was not severe and soon disappeared. Abnormal laboratory data due to the drug were not observed. PMID- 2239587 TI - [Clinical effect of oxybutynin hydrochloride (1 mg/tablet)]. AB - The clinical efficacy of oxybutynin hydrochloride was studied on 21 patients with neurogenic bladder or unstable bladder complaining of urinary frequency, urgency and urgent incontinence. Oxybutynin hydrochloride (1 mg/tablet) was administered orally for 26.7 days, on average, 3 mg per day in 3 and 6 mg per day in 18 patients and the usefulness of this drug was assessed subjectively and objectively. Of 21 patients treated, 9 had neurogenic bladder and 10 had unstable bladder. Urinary frequency was normalized in 6 out of 16 (37.5%), urgency ceased in 6 out of 17 (35.7%) and urgent incontinence disappeared in 9 out of 14 (50%) patients. The mean volume at the first desire to void and the maximum cystometric capacity increased significantly on the cystometrogram after the administration of oxybutynin hydrochloride (p less than 0.01). Furthermore, the maximum vesical pressure decreased significantly (p less than 0.05). The maximum urinary flow rate increased slightly (p less than 0.1) and the residual urine volume significantly increased (p less than 0.05) after medication, although no changes were observed in tidal voiding volume or mean urinary flow rate. Of 20 patients, 9 showed improvement globally (45%), although no subjective or objective improvement was observed in 4 (20%) patients. Marked side effects were observed in 5 cases (two of acute urinary retention, each of increased urgency, residual urine and liver dysfunction), and side effects were seen in 10 of the 21 (47.6%) patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239588 TI - [Comparative study of the patients with renal cell carcinoma before and after 1980]. AB - Patients with renal cell carcinoma treated at Jikei University and affiliated institutions were studied with regard to temporal differences. Our study population was divided into two groups: an earlier group comprising 169 patients treated between January 1957 and December 1979, and a later group comprising 165 cases treated between January 1980 and December 1984. The mean age in the earlier group was 56.2 years, while that in the later group was 60.4 years. Therefore, the patients in the earlier group were generally younger than those in the later group. Patients in the earlier group were more likely to present with urinary symptoms at the time of diagnosis. On the other hand, patients in the later group were more likely to present with extra-urinary symptoms or to be asymptomatic. The time period between the onset of symptoms and initial consultation with physician was longer (within one month) in the earlier group. Most patients in the later group underwent nephrectomy using the transperitoneal or thoracoabdominal approach. Few patients in the later group were treated with radiotherapy. As adjuvant chemotherapy, MFC (MMC, 5-FU and Ara-C) or MACV (methotrexate, actinomycin D, cyclophosphamide and vincristine) regimen were most commonly employed in the earlier group. FAV (5-FU, adriamycin and vinblastine) regimen or interferon therapy which was classified as biological response modifiers (BRM) were more commonly employed in the later group. More cases were diagnosed as stage II in the earlier group, and more cases were diagnosed as stage IV in the later group. No significant differences were observed between the earlier and later groups, with regard to 5- and 10-year survival rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239589 TI - [Clinical study of extracorporeal shock wave lithotripsy for 1000 patients with renal and ureteral stones]. AB - Using a Dornier HM3 lithotripter, we treated 1,000 patients with renal and ureteral stones from April, 1986 to July, 1989. They consisted of 612 solitary stones (pelvic stones, 152; calyceal stones, 167; ureteral stones, 293), 265 multiple stones and 123 staghorn calculi (complete, 48; partial, 75). The overall rate of the auxiliary procedure was 59.3% (pre-operative, 47.9%; post-operative, 11.4%). Pre-operative procedure included 430 catheterizations, 26 percutaneous nephrostomies (PNSs) and 23 pyelograms . Post-operative procedure included 69 transurethral lithotripsy , 21 PNSs, 26 percutaneous nephrolithotripsy (PNLs), 6 meatotomy , 5 chemolysis and 1 open surgery. 484 (68.3%) in 709 good follow-up cases were stone-free at the time of 3 months since the first extracorporeal shock-wave lithotripsy (ESWL). Complications were pain (34.8%), fever (4.3%), pain & fever (8.5%), subcapsular hematoma (0.1%) and ureteral obstruction (0.1%). Thus, ESWL is considered to be a useful means for renal and ureteral stones and in the case of large stone the combination therapy with PNL is more effective than ESWL-monotherapy. PMID- 2239590 TI - [Clinical studies on hyperuricemia and gout after transplantation]. AB - We performed renal transplantation on 67 patients (living 37, cadaver 30) between November 1975 and December 1987. Twenty-seven of the 67 patients had hyperuricemia (serum uric acid: male greater than or equal to 8.0 mg/dl, female greater than or equal to 7.0 mg/dl) and 2 of them had episodes of gout. However, there was no correlation between serum creatinine and uric acid in 27 hyperuricemic patients. Twelve of 27 hyperuricemic patients were treated with either allopurinol or benzbromarone. These therapies were effective for 9 of them and serum uric acid level controlled well. One of 2 gouty patients developed gout 4 years after cadaveric renal transplantation. She was treated with anodyne and benzbromarone for gout. These treatments were effective and she has been in good condition. We consider it necessary to treat hyperuricemia after renal transplantation and to control serum uric acid well. PMID- 2239591 TI - [Stereological estimation of mean nuclear volume in bladder cancer--measurement by point sampled intercepts]. AB - To obtain objective information about bladder cancer, we measured the mean nuclear volume of bladder cancer cells by using the "Point Sampled Intercepts" method, which was published by Gundersen et al. Thirty one cases of bladder cancer were selected and divided into 2 groups: group A; no recurrence over 3 years after initial TUR (12 cases), group B; cystectomy or cancer death (19 cases). Estimated mean nuclear volume was significantly smaller in group A than in group B. It is suggested that estimation of the mean nuclear volume by this stereological method may provide objective information for predicting the prognosis of patients with bladder cancers. Further studies in additional patients are required to substantiate the predictive potential of this method. PMID- 2239592 TI - [A comparative study of the effects of propiverine, terodiline, oxybutynin on the lower urinary tract function in the decerebrate dog]. AB - The effects of propiverine, terodiline, oxybutynin on the lower urinary tract function was studied by cystometry in 44 decerebrate dogs. Micturition was induced by bladder filling before and after the intravenous administration of each drug. The statistical analysis was carried out on the urodynamic parameters. Propiverine at a dose of 5, 10 mg/kg significantly increased the bladder volume. And, there was a substantial increase in the functional bladder volume at a dose of 10 mg/kg. Terodiline at a dose of 5 mg/kg also significantly increased the bladder volume and residual volume. Oxybutynin at a dose of 0.5 or 1 mg/kg produced a substantial increase in the bladder volume and residual volume, and produced a significant decrease in contraction pressure. Furthermore, there was a significant decrease in the functional bladder volume at a dose of 1 mg/kg. This study compared the three drugs under the same test conditions. Only propiverine increased the functional bladder volume, thus suggesting promise for the relief of pollakisuria in the clinical applications. PMID- 2239593 TI - [Correlation between histologic grading and prognosis of prostatic cancer- comparing the grading system of the Japanese general rules of prostatic cancer with Gleason's grading]. AB - To evaluate the correlation between the histological grade and the prognosis, we reviewed 100 cases of prostatic cancer according to the Japanese General Rules of Prostatic Cancer (JGRPC) and Gleason grading system. The study led to the following results: (1) There was a close relation between the JGRPC grade and Gleason score (GS). (2) The JGRPC grade and Gleason score were equally concerned with the clinical stage. (3) There were significant differences in survival rate between well and moderately, well and poorly differentiated groups by the JGRPC grading system, and between GS 2-4 and GS 5-7, GS 2-4 and GS 8-10 groups by Gleason score. (4) In proportion to the JGRPC grade, the cancer death rate increased linearly in each stage. (5) When the patients were grouped according to their JGRPC grades of main lesion and accompanied lesion, the cancer death rate increased in the cases with lower differentiated elements. We conclude that the JGRPC grading system is easily comprehensible, and equal with the Gleason grading system to predict the prognosis of prostatic cancer. PMID- 2239594 TI - [Bladder metastasis from renal cell carcinoma three years after nephrectomy]. AB - A 47-year-old man presented with gross hematuria. He underwent right nephrectomy for renal cell carcinoma (clear cell subtype, pT1N0M0) three years ago. Cystoscopy revealed a solitary, non-papillary tumor in the middle of the inter ureteric ridge. Transurethral resection of the tumor was done. Histological diagnosis was renal cell carcinoma (clear cell subtype). This was considered to be a metastatic tumor from the renal cell carcinoma treated three years earlier. This case may represent a so-called latent distant metastasis. PMID- 2239596 TI - [A case of multiple renal leiomyoma located at renal sinus and hilus]. AB - A case of multiple renal leiomyoma of the right kidney in a 60-year-old woman, complaining of lower abdominal pain of two months duration, is presented. Ultrasonography, intravenous pyelography and CT scan showed the masses at the right renal sinus and hilus. Selective right renal angiography demonstrated very hypovascular tumors. Right radical nephrectomy was performed. There were two lobulated tumors with no connections, which were elastic hard in consistency and smooth in surface; one was 4 x 2 x 2 cm in size and located at the renal sinus between the upper and middle calyces, the other was 6.5 x 5 x 4 cm in size and located at the renal hilus, apart from the renal parenchyma, pelvis, artery and vein. Histological examination revealed these tumors to be benign leiomyoma. Both were covered with the Gerota's fascia, but not the renal capsule. The renal parenchyma was completely covered with the renal capsule histologically, although these tumors were closely attached to the parenchyma on gross examination. The tumor at renal sinus was considered to arise from the outer layer of the renal pelvis or from the blood vessel in the connective tissues at renal sinus. The tumor at renal hilus was considered to arise from the blood vessel in the connective tissues at renal hilus. This appears to be the first reported case as multiple renal leiomyoma in both Japanese and English literatures. PMID- 2239595 TI - Complete resolution of multiple pulmonary metastases of renal cell carcinoma following intravenous drip infusion of r-interleukin 2: a case report. AB - A 68-year-old man with multiple pulmonary metastases from a right renal cell carcinoma was treated with alpha interferon, but there was no improvement. For this reason, alpha interferon was ceased, and daily monotherapy with recombinant interleukin-2 (1,000,000 units/day) was commenced. After 4 months, plain chest x ray and chest CT revealed complete clearance of the pulmonary metastases. There were no side effects except general fatigue and slight fever. Immunological studies revealed elevation of the leukocyte count (lymphocytes, eosinophils) and enhancement natural killer activity. At 10 months after discontinuation of the drug, recurrence has not been observed. Our case indicates the potential value of interleukin-2 following treatment with alpha interferon. PMID- 2239597 TI - [A case of renal pelvic tumor due to phenacetin abuse]. AB - An 80-year-old female had been taking phenacetin-containing analgesics due to severe pain in her legs and headache caused by SMON since 1957. The total accumulated dose of phenacetin that she had taken was about 2.3 kg. She visited the department of urology in our hospital complaining of gross hematuria in May, 1987. DIP showed that bilateral kidney were atrophic and her left pyelogram was non-visualized. A solid mass was located in her renal pelvis on the CT scan. Under the diagnosis of a left renal pelvic tumor, nephrectomy was performed on her left kidney in January, 1988. Histological diagnosis was interpreted as a transitional cell carcinoma, at a grade 1 greater than 2 and interstitial nephritis was detected. She died 8 months after the operation because of lung and bone metastasis. In autopsy, interstitial nephritis of the right kidney was also recognized. Our case is the fourth report of renal pelvic tumor due to phenacetin abuse in Japan. PMID- 2239598 TI - [Transitional cell carcinoma of the ureter with an inverted growth pattern which was accompanied with bladder tumor: a case report]. AB - The patient was a 75-year-old man who complained of macrohematuria which had set in from April 12, 1988. Under the clinical diagnosis of bladder tumor, total cystectomy with ureterosigmoidostomy was performed on June 25. During his surgery, we discovered a polypoid lesion of the right ureter close to the common iliac artery. The tumor was peanut-sized and had a stalk suggesting benign nature, so we resected it. Postoperative pathological examination revealed the tumor was transitional cell carcinoma (grade 2) with an inverted growth pattern. Though we could find no signs of tumor recurrence, the presence of tumor's residuum could not be ruled out. We performed nephroureterectomy of the right side on December 19. Follow-up on July 1, 1989 this patient revealed no tumor recurrence. PMID- 2239599 TI - [A case of emphysematous cystitis]. AB - Emphysematous cystitis is a rare but interesting disease. A case is reported of cystitis emphysema with acute pyelonephritis and uncontrolled diabetes. The patient was a 54-year-old woman complaining of gross hematuria and fever. A submucosa emphysema in bladder was found by cystoscopy . Radiography showed the gas around the bladder. The patient was administered antibiotics, then symptoms was improved. We reviewed 12 cases of emphysematous cystitis reported in Japan and summarized the pathophysiologic features of this entity. PMID- 2239601 TI - [A case of cystic lymphangioma grown in subcutaneous tissue of the pubis]. AB - A 37-year-old man visited our hospital with the chief complaint of a painless mass in subcutaneous tissue of the pubis. We extirpated the localized cyst 2.5 x 4 cm in size. Histological diagnosis was cystic lymphangioma without malignant findings. We reviewed the literature on lymphangioma, a rare disease seldom seen in urological fields. PMID- 2239600 TI - [Granulomatous prostatitis after intravesical BCG immunotherapy of superficial bladder cancer: a case report]. AB - We report a case of granulomatous prostatitis after intravesical BCG immunotherapy for superficial bladder cancer. A 58-year-old man presented with gross hematuria. Cystoscopic examination revealed multiple tumors at the posterior wall of the bladder. The patient underwent transurethral resection of the tumor. Intravesical BCG immunotherapy was postoperatively followed and it eradicated the disease. Digital examination revealed that the prostate became stony-hard and larger 10 weeks after the initial BCG immunotherapy. A needle aspiration cytology and biopsy of the prostate revealed the granulomatous prostatitis due to BCG immunotherapy. PMID- 2239602 TI - Leiomyoma of the scrotum: a case report and sonographic findings. AB - A rare case of leiomyoma of the scrotum is presented, and its ultrasonographic features are described. The ultrasound was of great help in the successful management by simple excision of the tumor. PMID- 2239603 TI - [Clinical study of iohexol in excretory urography]. AB - Excretory urography was performed using iohexol (Omnipaque 300 and Omnipaque 350) on 388 patients requiring urography in the Department of Urology, Nagoya University School of Medicine and 10 affiliated hospitals. Adverse reactions were observed in 3 cases (0.8%), but they were all mild. Good image efficacy was obtained in more than 95% of the patients injected 20 ml, 40 ml, and 100 ml of Omnipaque 300 and 40 ml of Omnipaque 350. There was no difference in the results of image efficacy between 40 ml (Omnipaque 300) and 100 ml (Omnipaque 300) groups. Therefore, the use of 40 ml of Omnipaque 300 for excretory urography was considered to be a very useful screening method for the urinary tract. PMID- 2239604 TI - [Clinical application of Therasonic lithotripsy treatment system for upper urinary tract calculi]. AB - Extracorporeal shock wave lithotripsy (ESWL) using a Therasonic lithotripter was performed on 30 patients with urinary tract calculi between July, 1989 and February, 1990. The results obtained in 31 cases (one patient had bilateral renal stones) were presented. There were 22 inpatients and 8 outpatients in this series. The stone location was: renal pelvis in 15 cases, renal calyces in 10 cases, parenchyma or diverticulum of renal calyces in 3 cases, ureteropelvic junction in 1 case, and upper ureter in 2 cases. Sixteen cases (52%) became stone free and residual stones (less than or equal to 4 mm) remained in 9 cases (overall effective rate 81%) at one month after the treatment. There were no serious complications including bacteremia and renal hematoma. We concluded that Therasonic lithotripter is useful in the management of upper urinary tract calculi. PMID- 2239605 TI - [Treatment of urinary stones with Therasonic, the third generation piezoelectric shock wave lithotripter]. AB - The THERASONIC lithotripsy treatment system, a newly developed piezoelectric lithotripter, uses both an X-ray and ultrasound system and enables stone localization effective. Treatment of urinary stones with THERASONIC was begun in June, 1989 and 57 treatments have already been performed on 38 patients. Successful treatment, defined as either stone free or with a residual stone less than 4 mm in diameter on flat X-ray film, was accomplished in 95% of the renal stones and over 50% of the ureteral stones. The overall success rate was 74%. Blood pressure and laboratory values did not show any significant change during or after the treatment. No major complication has been observed except for one perirenal hematoma which was resolved with conservative therapy. PMID- 2239606 TI - [Clinical statistics of the bladder tumor--clinical and pathological aspects of 325 cases]. AB - We analyzed 325 primary bladder tumor patients who were treated in our hospital during the past 15 years. There were 242 males and 83 females who were between 20 and 84 years old with an average age of 63 years old. The most frequent complaint was macroscopic hematuria in 76.9% of the patients (250/325). Cystoscopically, a single tumor was seen in 71%, the tumor was medium sized (1 to 3 cm) in 32%, and 56% were papillary tumors with a stalk. Histologically, 300 (92.3%) cases were transitional cell carcinoma. There were 42, 206 and 52 patients with grades 1, 2 and 3 transitional cell carcinoma and stage Tis, Ta, T1, T2, T3a, T3b, T2-4M1 and Tx were 2,46, 151, 30, 15, 16, 37 and 3 cases each. Transurethral resection was performed in 231 (71.1%), partial cystectomy in 6 (1.8%) and total cystectomy in 44 (12.5%) cases each. PMID- 2239607 TI - [Clinical statistics of the bladder tumor--survival rates of 325 cases]. AB - To study the relationship between clinical features and prognosis of the bladder tumor, 325 patients who were treated in our hospital were analyzed. The overall 5 year and 10-year actual survival rates were 65% and 51%. There was no statistical significance in the actual survival rate between the single and multiple tumor group. Although, there was a significant difference in tumor size, tumor growing type and the mode of treatment. The ten-year survival rates for grades 1, 2 and 3 cases were 76%, 57% and 18%, respectively. There was a significant difference between grades 1 and 3 (p less than 0.001) and grades 2 and 3 (p less than 0.001). The ten-year survival rates for stages Ta, T1, T2, T3a, T3b and T2-4 M1 were 79%, 68%, 43%, 0%, 19% and 5%, respectively. There was a significant difference between the Ta, 1 and T2-4 group (p less than 0.001). PMID- 2239608 TI - [Clinical statistics of the bladder tumor--transurethral resection cases]. AB - Two hundred and thirty one patients who underwent transurethral resection of a bladder tumor (TUR-Bt) at our hospital during the past 15 years were analyzed. There were 176 males and 55 females, and the average age at the initial TUR-Bt was 62 years old. Histopathologically, 225 cases were of transitional cell carcinoma, 4 cases of papilloma and 2 cases of squamous cell carcinoma. Grading and staging of 225 transitional cell carcinoma cases revealed grades 1, 2 and 3 in 32, 132 and 21 cases, and stages Ta, T1, T2, T3 and T2-4M1 in 48, 135, 20, 17 and 11 cases, respectively. The frequency of TUR-Bt varied from 1 to 10 times. Among the 231 cases TUR-Bt was done once, twice and three times in 149 (64.5%) and 41 (17.8%), and 22 (9.6%) cases, respectively and the total number of TUR-Bt was 400 times. The duration of the TUR-Bt operation was from 5 min. to 160 min. (mean: 32.4 min.) and the resected weight of tumor between 0.5 g and 85 g (mean: 5.4 g). As a complication of TUR-Bt, TUR-fulguration was necessary to control postoperative bleeding in 7 cases (1.7%), and blood transfusion was required in 13 cases (3.3%) during TUR-Bt. Postoperatively blood transfusion was required in 8 cases (2%), intraperitoneal perforation in 2 cases (0.5%), extraperitoneal perforation in 6 cases (1.5%) and hyponatremia in 1 case (0.3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239609 TI - [Prognosis of the patients with prostate cancer clinically confined within the pelvis]. AB - Between 1975 and 1989, 90 patients with prostate cancer in clinical stage A2 to C underwent pelvic lymphadenectomy. Median follow-up period was 38 months. Almost all of the patients with pN0-1 (49) and 4 of pN2 were treated by curative treatment, such as radical prostatectomy (7) or radiation therapy (45). The remaining pN2 (26), pN3 (4) and pM1 LYM (6) received endocrine therapy. Pelvic lymph node metastasis were noticed in 50 cases (56%). Rates of positive node and degree of nodal extension were related to clinical stage and histological grade. Disease-free survival of the patients with pN0-1 was better than that of the patients with more than pN2. There was no difference in disease-free survival between the patients with pN0 and pN1. We concluded that the patients with pN0 and pN1 were the candidates for curative therapy and recommend that the patients with more than pN2 be treated with endocrine therapy. PMID- 2239610 TI - [Effects of trospium chloride on the lower urinary tract function]. AB - The effects of trospium chloride on the lower urinary tract function were studied by combined recording of cystometry and sphincter electromyogram in 13 decerebrated dogs. Micturition was induced by bladder filling before and after drug administration. A statistical analysis was carried out on the urodynamic parameters. Trospium chloride at the dose of 0.1 mg/kg showed a small but significant decrease in the threshold pressure during the collecting phase. In the urodynamic parameters of the emptying phase which is considered to be influenced by cholinergic activity, there was a significant decrease in maximum bladder pressure at 0.03, 0.1, and 0.3 mg/kg and a significant increase in residual urine at 0.3 mg/kg. Trospium chloride is probably acting as a antimuscarinic agent in this study. Trospium chloride appears to be useful for the relief of symptoms associated with hyperactive bladder contraction. PMID- 2239611 TI - [Clinical study of asymptomatic microhematuria]. AB - A statistical survey was performed on 200 patients with asymptomatic microhematuria who visited our hospital between January 1986 and October 1989. Urinalysis, urinary cytology, urinary culture, IVP, echography and cystoscopy were carried out for the evaluation of the origin and nature of the microhematuria. In 92 patients (46%), urological abnormalities were observed. Among them, urological lesions requiring medical and surgical treatments were found in 28 patients (14%) including two malignant cases of bladder tumor. No urologic lesion could be identified in 108 patients (54%). The degree of hematuria was unrelated to the seriousness of its cause. Thirteen of 28 patients (46%) with diseases that required treatment had under 5 red blood cells per high power field on the microscopic urinalysis. Therefore, complete urologic investigation of all patients with any degree of asymptomatic microhematuria is recommended. PMID- 2239612 TI - Transitional cell carcinoma with adeno-squamous carcinoma component of renal pelvis in horseshoe kidney: a case report. AB - A case of renal pelvic transitional cell carcinoma accompanied by an adeno squamous carcinoma component in a horseshoe kidney is reported. This case is the first case reported in Japan to the best of our knowledge. PMID- 2239613 TI - [Percutaneous drainage of renal and perinephric abscesses]. AB - Two patients with renal or perinephric abscess were successfully managed by percutaneous drainage under ultrasonic guidance. We recommend percutaneous drainage as the first choice of treatment for a renal or perinephric abscess instead of traditional open surgery, especially in a high risk patient. PMID- 2239614 TI - [Unilateral hydronephrosis with hypertension due to ureteral endometriosis]. AB - A 35-year-old female patient was hospitalized for a headache. She was referred to our department for the evaluation of right hydronephrosis noted on the excretory urogram which was performed as part of a hypertensive diagnostic study. Endocrine examination revealed renal hypertension. Excretory urogram and antegrade pyelography showed obstruction of the lower part of the right ureter. On surgical exploration, the lower part of the right ureter was surrounded by brown tissue. Complete hysterectomy and ureterovesiconeostomy were performed. Histologically, the brown tissue around the ureter was diagnosed as endometriosis. One year after the operation, excretory urogram showed normal urinary tract and the blood pressure was 130/80 mmHg. Endometriosis is a common gynecological disease but ureteral endometriosis is relatively rare. Review of the Japanese literature disclosed 16 previous cases of ureteral endometriosis and we report the 17th case with a review of the literature. PMID- 2239615 TI - [A case of giant prostatic cystadenoma]. AB - An 80-year-old man was admitted to our hospital with the chief complaint of urinary retention. On physical examination, a large tumor was recognized in pelvic cavity. Serum levels of prostatic acid phosphatase and gamma-seminoprotein were elevated. Anterior pelvic exenteration was performed because the tumor was huge and malignancy could not be ruled out preoperatively. The tumor weight was 660 g (11 x 8 x 7 cm) and had a multicystic structure macroscopically. Immunohistochemical study by the prostatic specific antigen stain showed positive staining in the epithelial cells of the tumor, which suggest that the tumor was of prostatic origin. PMID- 2239616 TI - [Two cases of congenital urethral stenosis complicated with vesicoureteral reflux]. AB - Secondary vesicoureteral reflux (VUR) is not uncommon, but is rarely accompanied by congenital urethral stenosis in children. We report 2 cases. Case 1 was in a 3 year-old boy who had congenital anterior urethral stenosis accompanied by VUR. Urethroplasty by Johanson's operation was performed and 6 years later VUR disappeared. Case 2 was in a 7-year-old girl, who had congenital peripheral urethral stenosis accompanied by VUR. The urethra was dilated by a balloon dilator and about 1 year later VUR disappeared. PMID- 2239617 TI - [Cavernous hemangioma of the penis: report of a case immunohistochemically studied]. AB - An 18-month-old boy was admitted in April, 1988 because of a penile mass which had been first noted at the age of one month. From nine months after birth, transient bleeding from the mass accompanied by pain had been occasionally noted. At the age of 14 months, the mass seemed to grow markedly. On physical examination, there was an irregularly shaped mass on the right side of the prepuce. It was palpated subcutaneously, soft in consistency and was 10 mm in diameter. It had a light-purple color. Upon surgery, the mass was found not to have originated from the cavernous body of the penis, so that it could be excised without difficulty. Histopathological diagnosis was cavernous hemangioma. Electron microscopic examination revealed findings suggestive of newly formed blood vessels such as abnormal cuboidal shape of endothelial cells and a high nucleocytoplasmic ratio. Immunohistochemical examination of factor VIII-related antigen was in homogeneously positive in vascular endothelial cells. To our knowledge, this is the twenty-eighth case reported in Japan. PMID- 2239619 TI - [Castleman disease in the pelvic retroperitoneum]. AB - About 50% of the cases with Castleman disease firstly described by Castleman in 1956 occur in the thoracic cavity. The pelvic cavity is a rare location affected by the disease; there are only 7 reports. Herein, a case of Castleman disease of the pelvic cavity is reported. A 41-year-old man complaining of microscopic hematuria consulted us. Drip intravenous pyelography and computerized tomography showed a solitary mass at the pelvic retroperitoneum. Abnormal laboratory findings were as follows; glucose tolerance test (GTT), erythrocyte sedimentation rate, alpha 2-globulin level, CRP titer and hematuria. With the diagnosis of a pelvic retroperitoneal tumor, pelvic exploration was performed. The resected tumor was encapsulated, elastic hard and 4x3x2 cm in size. The cut surface was homogeneously granular and yellowish white in color. Histological diagnosis was the plasma cell type of Castleman disease. Within three weeks after the operation, laboratory abnormalities diminished except for GTT and microscopic hematuria. The patient is free from the disease with no signs of recurrence for 2 years postoperatively. PMID- 2239618 TI - [A case of paratesticular rhabdomyosarcoma]. AB - A case of paratesticular rhabdomyosarcoma in an 18-year-old male is reported. The patient was admitted for swelling of the right scrotum and right inguinal pain. Malignant tumor of the right testis was suspected and a high inguinal orchiectomy was performed. The pathological diagnosis was paratesticular rhabdomyosarcoma. Following retroperitoneal lymph node extirpation, chemotherapy, so-called CYVADIC therapy, consisting of cyclophosphamide, vincristine, adriamycin and dacarbazine was employed in 3 regions. The patient is in good health without recurrence 16 months after the surgery. PMID- 2239620 TI - [A case of Fournier's gangrene: was it triggered by prostatic massage?]. AB - We have experienced a case of Fournier's gangrene which progressed rapidly after prostatic massage. The patient was a 70-year-old man who had poorly controlled diabetes mellitus, hemorrhoid, urethral stricture and benign prostatic hyperplasia. He visited an urologist complaining of pollakisuria and miction pain. Under the diagnosis of prostatitis, prostatic massage was performed. From that night, he developed a high grade fever. Simultaneously, redness, swelling and pain of the scrotum progressed rapidly, and 11 days later, he was admitted to our hospital. An X-ray examination revealed subcutaneous gas formation in the scrotum. Immediately, incision and drainage with extensive debridement of necrotic tissue were performed combined with chemotherapy using broad spectrum antibiotics and insulin therapy. About 3 months later, the gangrene and the wound were healed with granulation and scarring. Cultures of the pus and the necrotic tissue from the scrotum were positive for Bacteroides fragilis and several aerobes including Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus and Staphylococcus epidermidis. The case proved to be non-clostridial gas gangrene. PMID- 2239621 TI - [Plasma methotrexate concentrations in urothelial cancer chemotherapy]. AB - The plasma methotrexate (MTX) concentration was measured during 50 courses of chemotherapy on 26 urothelial cancer patients. A dose of 300 mg/body MTX was infused within 2 hours and plasma concentrations were measured at the scheduled times. Plasma level at the end of infusion was (2.3 +/- 0.8) x 10(-5) M/L, (2.9 +/- 1.9) x 10(-5) M/L at the 6th-hour, and (1.9 +/- 1.8) x 10(-7) M/L at the 24th hour after the infusion. The plasma MTX concentration values were inversely correlated with creatinin clearance. In 6 cases of Kock pouch bladder, clean intermittent self catheterization of urine caused no meaningful increase of MTX. PMID- 2239623 TI - Extradural spinal cord compression from metastatic tumor. AB - Extradural spinal cord compression (ESCC) as a consequence of metastasis from various primary cancers represents the most common type of malignant lesion affecting the spinal cord. It has been estimated that 5% of all patients with systemic cancer who are autopsied have pathologic evidence of tumor invading the extradural space. The incidence of ESCC is expected to increase due to improved survival of the cancer patient. The current approach to the diagnosis of ESCC depends upon the recognition of early symptoms and signs of spinal cord compression. Despite the increasing clinical awareness of these complications, irreversible loss of ambulation continues to occur in over half of these patients. Early diagnosis is critical since onset of spinal cord injury may be sudden, often progressing to irreversible paralysis in a period of hours. Consequently, physicians dealing with cancer patients must maintain a high index of suspicion. This paper analyzes prognostic factors based on our prospective study and emphasize the use of diagnostic tests in early recognition of ESCC before onset of neurologic deficits. PMID- 2239622 TI - [Percutaneous removal of renal and upper ureteral stones: clinical results and complications of 103 cases]. AB - We report the results and complications of 103 consecutive patients who underwent percutaneous removal of renal and ureteral stones. The overall clinical success rate was 80.6%. For the recent 33 cases in which UL-arm fluoroscopy was used, however, the success rate was as high as 87.9%, which was considered to be due to easier establishment of percutaneous direct access. The most common complications were bleeding (18.5%), extravasation (15.5%) and fever (9.7%). Four cases with significant bleeding required arteriography, but there were no sign of arteriovenous fistula nor pseudoaneurysms in any cases. To study renal parenchymal damage in the percutaneous procedures, plasma renin activities (PRA) were compared in 54 cases after six months. However, significant elevation of PRA did not occur in any case. PMID- 2239624 TI - The Alabama automated defibrillation pilot program. AB - The Alabama Chapter of the American College of Emergency Physicians is now sponsoring a pilot program using EMT-Basic equipped with semi-automatic ("smart") defibrillators for the treatment of cardiac arrest patients in the field. This article outlines the rationale for the program along with present status of results. PMID- 2239625 TI - Physician and provider obligations under the Medicare antidumping provisions. AB - The Medicare antidumping provision enacted in 1986 and revised in 1989 has serious implications, not only for hospitals, but also for physicians who provide care for emergency patients. In this article, the author discusses the obligations of health care providers under that provision, some recent developments under the emerging case law, and the implications of these developments for physicians. PMID- 2239626 TI - Nutrition counseling: guidelines for the practicing physician. AB - Americans thrive on news about food, nutrition, diets and fitness. Testimony to this phenomenon is the predominance of popular literature related to these topics in the print and broadcast media. All too often the emphasis is on overnight or simple solutions to complex problems. The public is an easy mark for the "health peddler" who lacks credentials but possesses effective motivational skills and speaks with conviction about unfounded promises and exaggerated outcomes. Nutrition misinformation wastes billions of dollars every year but the greatest harm occurs when needed medical intervention is delayed or ignored. Patients expect physicians to be able to answer nutrition related questions and to know where to refer them for further nutritional guidance when needed. (1) In order to assure appropriate referrals, physicians need to know where to find a qualified dietitian/nutritionist and how to verify appropriate credentials. When a patient is referred to a dietitian for nutrition assessment and counseling, the expectations should be clear to all concerned and should include a plan for follow-up communication. This article describes the basis for and benefits of a partnership between the physician and dietitian in providing quality health care and patient education. PMID- 2239627 TI - Mucormycosis: a community hospital perspective. AB - Mucormycosis (synonymous with phycomycosis and zygomycosis) is a devastating fungal infection which usually involves patients with diabetes mellitus, often complicated by ketoacidosis, and malignant neoplasms, commonly leukemia and lymphoma. Clinical manifestations include rhinocerebral, pulmonary, disseminated, isolated cerebral, gastrointestinal and cutaneous disease. Common to all forms of mucormycosis is vascular invasion with production of necrotic tissue. The diagnosis is achieved by demonstrating broad, non-septate hyphae with right-angle branching in a tissue biopsy specimen. Successful treatment consists of early diagnosis, intensive systemic antifungal therapy with amphotericin B, aggressive surgical debridement and control of the underlying disease. In our experience with mucormycosis at Huntsville Hospital, the patients were immuno- compromised and the infection was restricted to the lung. Despite use of amphotericin B in all patients, the only one who survived underwent surgical section of infected tissue. PMID- 2239628 TI - A closer look. PMID- 2239630 TI - Why this time? PMID- 2239629 TI - The art of medicine. PMID- 2239631 TI - In-office physician laboratories. PMID- 2239632 TI - Clonidine dosage. PMID- 2239633 TI - Use of very-low-calorie diets in obesity. PMID- 2239634 TI - Nasolaryngoscopy for family physicians. AB - Nasolaryngoscopy is easy to learn and safe and convenient to perform. It is readily accepted by patients and is a rich source of clinical information. The flexible nasolaryngoscope allows the physician to directly observe the anatomy of the nasal passages, pharynx and larynx. The procedure is helpful for identifying the etiology of chronic nasal complaints and hoarseness. Other possible indications for nasolaryngoscopy include suspected nasal foreign body, recurrent nasal or pharyngeal bleeding, and epiglottitis. With the use of this instrument, treatment of otolaryngologic conditions may be more specific, thereby reducing unnecessary referral or delay in treatment. PMID- 2239635 TI - Measles update. AB - The incidence of measles in the United States dramatically increased in the 1980s, from a low of 1,497 cases in 1983 to over 17,000 cases in 1989. Family physicians can help reverse this trend by following the revised immunization schedule, which includes a measles-mumps-rubella (MMR) booster for preschool-age children. New guidelines also recommend that either the two-dose MMR schedule or serologic evidence of immunity be required for all persons entering college or employed in the medical field. Immunization policies for physician's offices should ensure that all office staff have acquired measles immunity and that a triage policy separating patients with rash from those with other illnesses is utilized. Mild upper respiratory illness, a history of seizures, nonanaphylactic egg allergy and asymptomatic human immunodeficiency virus infection are not contraindications to measles vaccine. All cases of measles should be reported to the local health department. PMID- 2239636 TI - Coarctation of the aorta. AB - Coarctation of the aorta is a common cardiovascular disorder with an unknown etiology. In the preductal type, blood flows from a patent ductus into the distal aorta. When the coarctation is juxtaductal or postductal, blood flows to the lower extremities by way of the subclavian arteries and collaterals. Plain films may show the reverse sign in postductal coarctation. Arteriography is the gold standard for making the diagnosis. However, magnetic resonance imaging will probably become an increasingly important diagnostic tool. The treatment of choice is surgery, with complete resection of the stenosed segment. PMID- 2239637 TI - Estrogen prophylaxis. The U.S. Preventive Services Task Force. AB - RECOMMENDATION: Although routine postmenopausal estrogen replacement is not recommended, estrogen therapy should be considered for asymptomatic women who are at increased risk for osteoporosis, who lack known contraindications and who have received adequate counseling about potential benefits and risks. PMID- 2239638 TI - Nutritional rickets. AB - Nutritional rickets was diagnosed in 18 infants aged eight to 24 months. Clinical features included progressive leg bowing, poor linear growth, a diet deficient in vitamin D, seizures, and abnormal serum calcium, phosphate and alkaline phosphatase levels. Wrist radiographs and serum alkaline phosphatase levels were the most useful confirmatory tests. Breast milk may not contain enough vitamin D to protect infants, particularly dark-skinned children and those living in cloudy, northern U.S. cities, from rickets after six months of age. As breast feeding becomes more widely practiced, care is required to ensure that infants at high risk for rickets receive appropriate vitamin D supplementation. PMID- 2239639 TI - Venous ulcers: pathophysiology and medical therapy. AB - Venous ulcers may occur as a result of lower extremity calf pump failure, with ensuing edema, trapping of white blood cells and deposition of pericapillary fibrin. Acute, smaller lesions are easily treated with adequate compression and occlusive dressings. Larger, more chronic wounds often benefit from some form of external compression. Occlusive dressings and local wound care are most effective when used simultaneously with compression. Sequential compression pumps merit study and may prove to be of therapeutic and prophylactic value. In refractory cases, long-term use of compression devices may be required to prevent ulcer recurrence. PMID- 2239640 TI - Constipation: pathophysiology and treatment. AB - Although many physicians consider constipation a trivial problem, it is one of the most frequent and chronic digestive disorders in the United States, affecting 4.53 million people and causing considerable morbidity. More than $200 million are spent for over-the-counter laxatives and untold millions of dollars are spent for prescription drugs and other medical services to manage this disorder. Successful management requires an appreciation of the magnitude of the problem, an understanding of colorectal function and a clear assessment of the causes. Careful examination of the patient's anorectal anatomy and improvement in the patient's dietary habits are the first steps in management. Therapeutic options include behavioral modification strategies, diet and lifestyle changes, pharmacologic therapy and, rarely, surgical intervention. PMID- 2239641 TI - Tartrazine sensitivity. AB - Tartrazine (FD & C Yellow No. 5) is an approved azo dye present in many drugs and food products. During the 1970s, many cases of tartrazine sensitivity were reported. This led to new regulations that required the listing of azo dyes on package inserts of drugs and on packages of food products. Tartrazine sensitivity is most frequently manifested by urticaria and asthma. Although azo dyes have been implicated in accentuating hyperkinetic syndromes, tartrazine is not considered an offender. Vasculitis, purpura and contact dermatitis infrequently occur as manifestations of tartrazine sensitivity. Cross-sensitivity in aspirin sensitive and NSAID-sensitive patients may also occur. The mechanism of sensitivity is obscure and has been called pseudoallergic. Management consists mainly of avoidance of drugs and food products that contain tartrazine. PMID- 2239642 TI - Family physicians can clarify issues for HIV-positive patients. PMID- 2239643 TI - Recommended core educational guidelines on alcoholism and substance abuse for family practice residents. American Academy of Family Physicians. PMID- 2239644 TI - NIH statement covers early breast cancer treatment. PMID- 2239645 TI - Methadone use for controlling HIV. PMID- 2239647 TI - Access to health care. PMID- 2239646 TI - Family physicians and a smoke-free society. PMID- 2239648 TI - Silent myocardial ischemia: dilemma or blessing? AB - Developing an optimal strategy for the evaluation and management of patients with silent myocardial ischemia is extremely difficult. Although otherwise healthy, asymptomatic individuals may be at risk of dying suddenly during exercise, neither exercise testing nor Holter monitoring reliably identifies those at greatest risk. In patients with underlying coronary artery disease, silent ischemia increases the risk of an adverse outcome. PMID- 2239649 TI - New perspectives in the management of Alzheimer's disease. AB - Alzheimer's disease is the most common cause of progressive dementia in older adults. Diagnosis is based on a careful history, a thorough physical examination and appropriate laboratory studies. Although the pathology of Alzheimer's disease is well described, the etiology remains unknown. The only well-established risk factors are advanced age and family history. Management problems frequently include depression, delirium, wandering, urinary incontinence and iatrogenic disease. PMID- 2239650 TI - Approaching the protein-sparing modified fast. AB - The protein-sparing modified fast is a safe and effective method for losing a large amount of weight relatively quickly. This diet should be used in combination with an exercise program, behavior modification and patient education. Caloric intake is in the range of 400 to 800 per day. Candidates for the diet should be generally healthy; they should have at least 40 lb to lose or be at more than 120 percent of their ideal body weight. PMID- 2239651 TI - Recognition and treatment of major depression. AB - Major depression is a syndrome that can be triggered by numerous physical and psychosocial factors. Concurrent somatic complaints can complicate the diagnosis. Patient evaluation requires a comprehensive history, physical and mental status examinations, and a number of laboratory studies. Effective treatment of depression enhances the quality of life, reduces the probability of secondary alcoholism or suicide, frequently improves coexisting medical problems and reduces the high rate of health care use by these patients. PMID- 2239653 TI - Initial evaluation of HIV-infected patients. PMID- 2239652 TI - Hypnosis in family medicine. AB - Hypnosis can be a useful adjunct to other treatment modalities. For example, hypnosis may induce a level of relaxation that allows patients to cooperate more easily with conventional treatment. The often dramatic historical background of hypnosis has led to misconceptions about hypnotic technique and its clinical applications in modern medicine. Hypnosis is useful in the treatment of acute and chronic pain, somatoform and habit disorders, anxiety and depression. Persons who are attempting to stop smoking, patients with bulimia and those with psychogenic impotence may respond to hypnosis. PMID- 2239654 TI - Persistent uptake of indium-111-antimyosin monoclonal antibody in patients with myocardial infarction. AB - Indium-111(111In)-antimyosin scintigraphy was investigated in 27 patients with myocardial infarction. 111In-antimyosin Fab was administered intravenously, and planar and single photon emission computed tomographic images were obtained 48 hours later. Uptake of 111In-antimyosin was present in 9 of 10 patients (90%) studied within 6 days of infarction. During the second week positive scans were seen in 16 of 16 patients (100%) including 13 (81%) who had normal creatine kinase levels. The mechanism of persistent positive antimyosin images in the subacute stage of myocardial infarction remains to be clarified. 111In-antimyosin scintigraphy may be useful as a noninvasive method for the detection of myocardial injury late and early after a suspected acute myocardial infarction. PMID- 2239655 TI - Coronary perfusion catheter: its effectiveness in an experimental model of acute coronary occlusion. AB - The effectiveness of a coronary perfusion catheter was studied in an animal model of acute coronary occlusion. Systemic hemodynamic variables, regional myocardial blood flow (RMBF) in the subepicardium and subendocardium, and regional systolic function (systolic segmental shortening) of the area perfused by the circumflex coronary artery (CX) were measured in eight anesthetized dogs. After baseline measurements, the CX coronary artery was occluded with a silk snare and measurements were repeated after 5 minutes of ischemia (occlusion No. 1). The snare was released and 1 hour later the snare occlusion was repeated after placement of a perfusion catheter in the CX coronary artery. After 5 minutes, measurements were repeated (occlusion No. 2). To determine the long-term effectiveness of the catheter, hemodynamic variables and regional function measurements were then obtained every 15 minutes for a total of 60 minutes. During occlusion No. 1, RMBF decreased from 1.30 +/- 0.20 to 0.41 +/- 0.13 ml.min 1.gm-1 (p less than 0.01), and subendocardial RMBF decreased from 1.44 +/- .24 to 0.34 +/- 0.15 ml.min-1.gm-1 (p less than 0.01). After insertion of the perfusion catheter (occlusion No. 2), subepicardial RMBF was maintained at 0.97 +/- 0.16 and subendocardial RMBF was maintained at 0.78 +/- 0.13 ml.min-1.gm-1; during occlusion No. 2 subepicardial RMBF was greater (p less than 0.05) than occlusion No. 1 and was not different from baseline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239657 TI - Left ventricular asynchrony: an indicator of regional myocardial dysfunction. AB - There is a marked heterogeneity of myocardial wall thickening within the left ventricle and among different individuals. It is therefore difficult to detect regional myocardial dysfunction from absolute values of systolic wall thickening. We tested whether the extent of left ventricular asynchrony during ischemia and reperfusion can be used to quantify the severity of regional myocardial dysfunction when nonischemic baseline function is not known. In six anesthetized, open-chest dogs regional myocardial wall thickness was measured by means of sonomicrometry under control conditions, at three degrees of ischemic dysfunction (mild, moderate, and severe), and after release of a 15-minute occlusion of the left circumflex coronary artery, when degrees of moderate and mild reperfusion dysfunction similar to the preceding ischemic dysfunction were present. Two indexes of left ventricular asynchrony were calculated: (1) postejection thickening (PET) and (2) the phase difference of the first Fourier harmonic of posterior versus anterior myocardial wall motion (PD). Systolic myocardial wall thickening was decreased from 15.3 +/- 3.1 (standard deviation) % (control value) to 9.7 +/- 1.4% (mild ischemia), 4.2 +/- 1.6% (moderate ischemia), and -3.7 +/- 3.1% (severe ischemia). Conversely PET increased from 0.02 +/- 0.04 mm (control value) to 0.15 +/- 0.22 mm (mild ischemia), 0.19 +/- 0.15 mm (moderate ischemia), and 0.50 +/- 0.26 mm (severe ischemia). PD increased from 9 +/- 28 degrees (control value) to 22 +/- 19 degrees (mild ischemia), 54 +/- 18 degrees (moderate ischemia), and 107 +/- 21 degrees (severe ischemia). After release of the 15 minute left circumflex coronary artery occlusion, PET and PD recovered to 0.34 +/ 0.19 mm and 36 +/- 24 degrees (moderate dysfunction) and 0.25 +/- 0.31 mm and 29 +/- 8 degrees (mild dysfunction), respectively. There were inverse linear relationships between systolic wall thickening and PET (r = -0.86, p less than 0.001) and between systolic wall thickening and PD (r = -0.87, p less than 0.001). Inotropic stimulation by postextrasystolic potentiation increased regional systolic myocardial posterior and anterior wall thickening but did not alter the extent of left ventricular asynchrony. Thus, when normal baseline function is not known, the severity of regional myocardial dysfunction at a given inotropic state can be determined by analysis of left ventricular asynchrony. There was no significant correlation between the extent of PET and PD during ischemia and at early reperfusion and the recovery of contractile function at late reperfusion. Thus PET does not provide a prospective marker for the functional outcome of reperfusion. PMID- 2239656 TI - Dose-dependent reduction of myocardial infarct size with the perfluorochemical Fluosol-DA. AB - The perfluorochemical Fluosol-DA has been shown to reduce infarct size. However, the dose-response relationship of the agent is unknown. Because perfluorochemicals (PFC) can potentially saturate the reticuloendothelial system and decrease carbon clearance as well as cause a transient elevation in liver enzymes, the present study was conducted to determine the lowest effective dose. New Zealand White rabbits (n = 73) were randomly selected prior to infarction to receive 10, 15, 20, 25, or 30 ml/kg PFC or an equivalent volume of 5% dextran (control) intravenously. Animals underwent 30 minutes of coronary artery occlusion with PFC or dextran infused over a 30-minute period starting at 20 minutes into the occlusion. Animals were put to death at 24 hours and infarct size was determined histologically and quantitated by computerized planimetry. Neutrophil infiltration into the ischemic myocardium was evaluated semiquantitatively. No hemodynamic differences were noted within groups. Infarct size was similar to that of controls in animals treated with 10 or 15 ml/kg PFC. Significant infarct size reduction, however, was noted in animals treated with 20, 25, and 30 ml/kg PFC versus controls; (p = 0.05, 0.04, and 0.02, respectively). Maximal infarct size reduction was seen with 30 ml/kg PFC (35%). Neutrophil infiltration was significantly decreased in all groups treated with PFC. These results show that intravenous Fluosol-DA significantly reduces infarct size at a minimal dose of 20 ml/kg. PMID- 2239658 TI - Detection and quantitation of ischemic left ventricular dysfunction using a new video intensity technique for regional wall motion evaluation. AB - Eighty patients with ischemic heart disease and 17 normal subjects were evaluated for left ventricular regional wall motion by means of a new method. The wall motion analysis is based on video intensity. This technique uses a temporally sliding analysis to evaluate the cardiac cycle in 100 msec intervals. Presence of coronary artery disease was defined as more than 50% measured diameter stenosis. Wall motion abnormalities in regions perfused by stenotic vessels were most common in early diastole (76%). Sensitivity of this method at rest in patients with coronary artery disease was 79.7% (p less than 0.0001) and overall accuracy was 84.2% (p less than 0.0001). Abnormalities in both systole and diastole were more common in regions perfused by severe lesions (greater than 75%) than in those perfused by moderately stenotic (less than 75%) vessels (p less than 0.05). A comparison of the new method with phase and amplitude analysis was performed in 15 patients and with two-frame analysis in 40 patients. This new method yielded a higher sensitivity than either of the other two methods. PMID- 2239659 TI - Silent myocardial ischemia and infarction in diabetics with peripheral vascular disease: assessment by dipyridamole thallium-201 scintigraphy. AB - We investigated the incidence of silent myocardial ischemia and infarction as assessed by dipyridamole thallium scintigraphy in 30 diabetic patients with peripheral vascular disease and without clinical suspicion of coronary artery disease. Seventeen patients (57%) had thallium abnormalities, with reversible thallium defects compatible with ischemia in 14 patients (47%) and evidence of prior, clinically silent myocardial infarction in 11 patients (37%). Thallium abnormalities were most frequent in patients with concomitant hypertension and cigarette smoking (p = 0.001). These results suggest that unsuspected coronary artery disease is common in this particular group of patients with diabetes mellitus. PMID- 2239660 TI - Coronary angioplasty in symptomatic patients after bypass surgery. AB - With the availability of percutaneous transluminal coronary angioplasty (PTCA), the management of patients who present with recurrent angina following coronary artery bypass surgery (CABG) has changed. From January 1987 to December 1988, 149 symptomatic post CABG patients underwent coronary angiography at our institution. Ninety were treated with medical antianginal therapy, 14 had repeat surgery, and 45 underwent PTCA. Complications of repeat CABG included one death, two perioperative myocardial infarctions, and four patients with postoperative supraventricular arrhythmia. PTCA was performed on 42 lesions in 37 native vessels (88% success rate), and on 24 lesions in 23 vein grafts (91.7% success rate). Complications included acute reocclusion (one patient), peripheral artery occlusion (one patient), hematoma formation (one patient), and periprocedure myocardial infarction (one patient). No deaths occurred. At a mean follow-up of 5.9 +/- 3.8 months, 10 patients had recurrent symptoms, six of whom were found to have restenosis. Repeat PTCA was successfully accomplished in four patients; the other two were treated medically. It is concluded that PTCA is a feasible alternative to repeat CABG in selected patients and can be achieved with a high success rate and minimal complications. PMID- 2239661 TI - Early assessment of coronary reserve after bypass surgery by dipyridamole transesophageal echocardiographic stress test. AB - The evaluation of coronary reserve within a few hours of aortocoronary bypass surgery could be of extreme utility for the follow-up or therapeutical management of these patients. In 11 men patients who underwent aortocoronary bypass surgery, a dipyridamole echocardiography stress test was carried out before (1 to 3 days), early after (68 to 130 minutes), and 1 week after surgery. The first and third tests were performed using a standard transthoracic approach, while the second was performed by a transesophageal approach. Dipyridamole was administered intravenously at a dose of 0.56 mg/kg body weight (low dose) and eventually adding 0.28 mg/kg body weight (high dose), always in the absence of antiischemic therapy. An arbitrary wall motion score (0 = eukinesia; 1 = hypokinesia; 2 = akinesia; 3 = dyskinesia) was assigned to the seven different myocardial regions in which the left ventricle was divided in order to have a semiquantitative score. Under basal conditions wall motion score per patient in the three series of tests did not change significantly (1.6, 1.4, and 1.5, respectively), while the mean score during dipyridamole administration showed significant differences (3.6, 1.9, and 1.9, respectively), indicative of the results obtained by surgical repair. The test, positive in all patients before surgery, showed wall motion abnormalities and ischemic ECG changes in two patients immediately after surgery by the transesophageal approach. One patient who had a normal basal contraction pattern and an abnormal response after the test developed in the following days a perioperative myocardial infarction, while a second patient in the follow-up period developed low-level effort angina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239662 TI - Clinical significance of simple heart rate-adjusted ST segment depression in supine leg exercise in the diagnosis of coronary artery disease. AB - To evaluate the clinical significance of simple heart rate-adjusted ST segment depression (delta ST/delta HR) in the diagnosis of coronary artery disease, 42 patients with stable exertional angina underwent supine leg exercise testing and cardiac catheterization. During exercise, heart rate, a multilead electrocardiogram, and pulmonary artery wedge pressure were recorded. The sensitivity and accuracy of the delta ST/delta HR criteria (greater than or equal to 3.0 microV/beat/min) were significantly greater than the conventional analysis of ST segment depression criteria (greater than or equal to 0.2 mV) for detecting three-vessel coronary artery disease at a matched specificity of 72% (100% versus 46%, 81% versus 64%, p less than 0.01). A significant linear correlation was found between maximum pulmonary artery wedge pressure increments during exercise (delta PAWP) or Gensini score and the delta ST/delta HR (delta PAWP: r = 0.51, p less than 0.001; Gensini score: r = 0.47, p less than 0.001). There were no statistically significant differences in the delta PAWP or Gensini score between patients with three-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min and those with one- or two-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min (delta PAWP: 18.1 +/- 2.0 versus 21.9 +/- 3.3, p = NS; Gensini score: 68.5 +/- 6.6 versus 66.3 +/- 11.3, p = NS). These findings demonstrate that delta ST/delta HR is more useful than a conventional analysis of ST segment depression for identifying not only anatomically severe coronary artery disease but also functionally severe coronary artery disease. PMID- 2239663 TI - Electrophysiologic effects of exogenous phosphocreatine in cardiac tissue: potential antiarrhythmic actions. AB - The cellular electrophysiologic effects of exogenous phosphocreatine (PCr) were analyzed to ascertain its purported antiarrhythmic properties during myocardial ischemia and reperfusion. Transmembrane potentials were recorded from isolated guinea pig papillary muscles and Purkinje fibers studied in vitro. Under control, normoxic conditions, 10 mmol/L PCr significantly increased the action potential duration (measured at 90% of repolarization) in ventricular muscle by 14.6 +/- 3.3 msec and the effective refractory period by 11.5 +/- 3.8 msec (both p less than 0.01). Under ischemic-like conditions (hypoxia, lactic acidosis, elevated [K+]o, zero substrate) PCr had no effect. Phosphocreatinine, a related compound that is not a direct substrate in the creatine kinase reaction, acted similarly to PCr suggesting that alterations induced by PCr did not involve a change in the energy state of cells. However, PCr reduced free [Ca2+]o by nearly 20%, and its electrical effects under normoxic conditions could be largely reversed by a concomitant 20% increase in [Ca2+]o. In Purkinje fibers superfused with low [K+]o Tyrode's solution to elicit conditions of Ca2+ overload, delayed afterdepolarizations and triggered responses were reversibly inhibited by PCr. These data suggest that the antiarrhythmic effects of PCr in situ may involve prolongation of the effective refractory period in nonischemic tissue or attenuation of membrane changes elicited by Ca2+ overload in ischemic cells. The mechanism by which PCr produces these effects may be related in part to changes in extracellular Ca2+ composition. PMID- 2239664 TI - ACE inhibition improves vagal reactivity in patients with heart failure. AB - The deranged autonomic control of heart rate was studied in 34 patients with heart failure (New York Heart Association [NYHA] functional class II to III) by examining the carotid sinus baroreflex. The carotid sinus baroreceptors were stimulated by graded suction. The slope of the regression line between increases in cycle length and the degree of neck suction was taken as an index of baroreflex sensitivity. The reflex response is mediated by a selective increase of vagal efferent activity. Baroreflex sensitivity therefore represents a measure of vagal reactivity. Using multiple regression analysis, baroreflex sensitivity (BS) correlated positively to stroke volume index (SVI) and inversely to plasma renin activity (PRA) and to age: BS = 0.47 SVI - 0.38 PRA - 0.23 age + constant (r = 0.74; p less than 0.0005). In addition to digitalis and diuretics, angiotensin-converting enzyme (ACE) inhibitors (captopril or enalapril) were given to 16 patients for a mean of 17 +/- 3 days. The patients with hemodynamic improvement (group A) exhibited improved baroreflex sensitivity (1.4 +/- 0.4 to 3.6 +/- 1.2 msec/mm Hg; p less than 0.01). Baroreflex sensitivity remained unchanged (3.1 +/- 0.8 to 2.4 +/- 1.0 msec/mm Hg; n.s.) in the patients without hemodynamic improvement (group B). The increase in reflex sensitivity did not correlate with hemodynamic alterations. Baroreflex sensitivity during ACE inhibition (BSD) was only related to the baseline baroreflex sensitivity (BSB): BSD = 2.8 BSB - 0.46 (r = 0.84; p less than 0.005). In patients with heart failure, reflex bradycardia decreases with age and with PRA and increases with stroke volume. Chronic therapy with ACE inhibitors enhances vagal reactivity in patients with hemodynamic improvement. PMID- 2239665 TI - Are ioxaglate and iopamidol equally safe and well tolerated in cardiac angiography? A randomized, double-blind clinical study. AB - A randomized, double-blind, parallel-group study was performed in 50 patients undergoing left ventriculography and coronary arteriography to evaluate ECG changes and the effects on left ventricular function of a low-osmolar ionic contrast agent, ioxaglate, as compared with a low-osmolar nonionic contrast medium, iopamidol. Twenty-five patients received ioxaglate (group 1) and 25 patients received iopamidol (group 2). All patients underwent 48 hours of continuous ECG recording beginning 24 hours before the cardiac catheterization. Left ventricular systolic and end-diastolic pressure, peak positive dp/dt, and dp/dt/P ratio were measured immediately before and after left ventriculography and 3 minutes later. Left ventricular systolic pressure did not change after injection of either contrast medium. Left ventricular end-diastolic pressure increased by 30% in group 1 (p less than 0.01) and by 22% in group 2 (p less than 0.01) immediately after left ventriculography. A further increase by 45% in group 1 (p less than 0.01) and by 24% in group 2 (p less than 0.01) was observed 3 minutes later. No differences were observed between values obtained in the two groups. Peak positive dp/dt did not change immediately after injection of either contrast medium but decreased by 5% (not significant) in group 1 and by 7% (p less than 0.02) in group 2 three minutes after left ventriculography. There were no significant differences between the two groups. Analysis of continuous 48-hour ECGs showed that both ioxaglate and iopamidol induced a slight increase (by 8% and 7%, respectively; p less than 0.05) in heart rate during injection with early and complete recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239666 TI - Color Doppler diagnosis of mechanical prosthetic mitral regurgitation: usefulness of the flow convergence region proximal to the regurgitant orifice. AB - In prosthetic or paravalvular prosthetic mitral regurgitation, transthoracic color Doppler flow mapping can sometimes fail to detect the regurgitant jet within the left atrium because of the shadowing by the prosthetic valve. To overcome this limitation, we assessed the utility of color Doppler visualization of the flow convergence region (FCR) proximal to the regurgitant orifice in 20 consecutive patients with mechanical prosthetic mitral regurgitation documented by surgery and cardiac catheterization (13 of 20 patients). In addition, we studied 33 patients with normally functioning mitral prostheses. Doppler studies were performed in the apical, subcostal, and parasternal long-axis views. An FCR was detected in 95% (19 of 20) of patients with prosthetic mitral regurgitation. A jet area in the left atrium was detected in 60% (12 of 20) of patients. In 18 of 19 patients with Doppler-detected FCR, the site of the leak was correctly identified by observing the location of the FCR. A trivial jet area was detected in eight patients with a normally functioning mitral prosthesis; in none was an FCR identified. Thus color Doppler visualization of the FCR proximal to the regurgitant orifice is superior to the jet area in the diagnosis of mechanical prosthetic mitral regurgitation. Moreover, FCR permits localization of the site of the leak with good accuracy. PMID- 2239668 TI - The effects of lying position on ventricular volume in congenital absence of the pericardium. AB - In patients with congenital absence of the left pericardium, the heart is supported by the existing right pericardium in the right lateral position, while it is not in the left lateral position. To investigate the change in ventricular size resulting from postural change, seven patients with this malformation were examined. Ventricular volumes were calculated by computed tomography, integrating areas of computed tomographic cross sections measured at 1 cm intervals from the cardiac apex to the aortic arch. In the right lateral position, right ventricular (RV) and left ventricular (LV) volumes were no different from those of five control subjects. With a change in the lying position to the left, the increase in the ventricular volume was significantly greater than that in the control subjects (35 +/- 11 versus 3 +/- 3 ml in the right ventricle and 15 +/- 13 versus 3 +/- 8 ml in the left ventricle). The increases in RV and LV end-diastolic pressure, however, were almost the same as those in the 11 control subjects. It is concluded that the cardiac ventricle, especially the right ventricle, dilates significantly with a small increase in preload in patients with congenital absence of the pericardium. It may be a clue for clarifying the ventricular distensibility being freed from physiologic restraint of the pericardium for a long period. PMID- 2239667 TI - Transesophageal echocardiography in the awake elderly patient: its role in the clinical decision-making process. AB - To assess the impact on the management and safety of transesophageal echocardiography (TEE) in the elderly population, the results and limitations of this technique were retrospectively analyzed in 88 patients. TEE was indicated whenever the transthoracic approach was not diagnostic or was inconsistent with the clinical setting. The most frequent clinical indications were to investigate the source of emboli, assess valvular regurgitation, and identify valvular vegetations. In 72 patients (82%) TEE significantly influenced management decisions. In selected patients TEE avoided the use of more invasive diagnostic procedures. Adverse effects included occasional premature atrial or ventricular beats (11 patients), sinus bradycardia (six patients), and protracted nausea (one patient). We conclude that in elderly patients with cardiovascular diseases, TEE plays a significant role in the decision-making process without adding a significant risk. PMID- 2239669 TI - Noninvasive assessment of cardiac output in children using impedance cardiography. AB - This study evaluated the effect of intracardiac shunting on the accuracy of thoracic bioimpedance-derived cardiac output determinations. Twenty-six patients, ranging in age from 3 months to 17 years, underwent cardiac catheterization during which simultaneous Fick and impedance measurements of cardiac output were obtained. The subjects were divided into three groups: 10 children with no intracardiac shunts, nine children with predominant left-to-right intracardiac shunts, and seven children with predominant right-to-left intracardiac shunts. Positive correlations between impedance and Fick-derived cardiac output determinations were obtained in the non-shunt group (r = 0.84), with lower correlations in the left-to-right shunt group (r = 0.70). In the right-to-left shunt group, the impedance derived cardiac output correlated with Fick pulmonary flow (r = 0.82), but the variability was unacceptably large. Although further study is needed, impedance cardiography appears to have validity as a methodology in pediatric critical care and cardiovascular health research. PMID- 2239670 TI - The evolving pattern of digoxin intoxication: observations at a large urban hospital from 1980 to 1988. AB - Digoxin intoxication has been reported to be a common adverse drug reaction with an in-hospital incidence of 6% to 23% and an associated mortality rate as high as 41%. A retrospective review was conducted to assess the accuracy of diagnosis, the morbidity and mortality of digoxin intoxication, and its incidence in hospitalized patients with heart failure. We reviewed the medical records of 219 patients discharged with the diagnosis of digoxin intoxication between 1980 and 1988. Patients were classified as follows: (1) Definite intoxication--patients with symptoms and/or arrhythmias suggestive of digoxin intoxication that resolved after discontinuation of digoxin; (2) possible intoxication--patients with symptoms and/or arrhythmias suggestive of digoxin intoxication in the absence of documented resolution after discontinuation of digoxin, or the presence of other clinical illnesses that could possibly account for those findings; (3) no intoxication--patients whose symptoms or ECG abnormalities were clearly explained by other associated clinical illnesses and persisted after withdrawal of digoxin. We identified only 43 patients (20%) with definite intoxication. The majority of patients discharged with the diagnosis of digoxin intoxication (133 or 60%) were classified as possibly digoxin intoxicated, and 43 patients (20%) had no clinical evidence to support this diagnosis. To estimate the incidence of digoxin intoxication, we also reviewed the medical records of 994 patients admitted in 1987 with heart failure. Of these, 563 were receiving digoxin and in 27 the diagnosis of digoxin intoxication was made by their clinicians. Our review showed that only four were definitely intoxicated (0.8%), and the diagnosis could not be excluded in another 16 (4%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239672 TI - A simplified method to measure coronary blood flow velocity in patients: validation and application of a Judkins-style Doppler-tipped angiographic catheter. AB - To facilitate more rapid and safe measurement of coronary flow velocity reserve in patients, we developed a Judkins-style angiographic catheter tipped with a 20 MHz Doppler crystal. In 19 patients without coronary artery disease, resting and hyperemic (10 mg intracoronary papaverine) mean and phasic coronary flow velocity signals were measured with the Judkins-style and 2.5F intracoronary Doppler catheters at identical coronary loci. Mean coronary flow velocity at rest was similar (14 +/- 8, 10 +/- 7 cm/sec, p = ns), but was higher during hyperemia for the Judkins-Doppler (41 +/- 8 versus 32 +/- 14 cm/sec, p less than 0.05). Coronary flow velocity reserve, calculated as the ratio of mean velocity at rest to mean velocity following papaverine, was 3.3 +/- 1.4 and 3.7 +/- 1.2 units (p = ns) for the Judkins and intracoronary Doppler techniques, respectively (r = 0.801, p less than 0.001). The Judkins-style Doppler catheter technique permits flow velocity and coronary flow velocity reserve measurements that correlate strongly with those of the intracoronary catheter technique, facilitating safe, quick, and accurate assessment of coronary physiology. PMID- 2239671 TI - Is obesity-related hypertension less of a cardiovascular risk? The Framingham Study. AB - The hypothesis that obesity-related hypertension is relatively innocuous was explored by an examination of cardiovascular events over 34 years of follow-up when related to biennially measured weights and blood pressures using time dependent covariate proportional hazards analysis. The 5209 participants were also classified by age, cigarette smoking, and antihypertensive treatment at each of four baseline examinations with 8-year follow-up periods. Over the period of follow-up, there were 978 cardiovascular events in men and 836 in women. Risk of cardiovascular morbidity and mortality in general and of CHD in particular was as strongly related to hypertension at all levels of body mass index. This was also found to apply when adjustment was made for possible confounding by cigarette smoking. Age and smoking-adjusted absolute risks of cardiovascular events were found to be higher in hypertensive individuals with high than with low BMIs. Furthermore, the relative risk of cardiovascular disease did not vary significantly with BMI. Thus hypertension is at least as dangerous in obese as in lean persons at all ages in either sex, providing no support for the hypothesis that hypertension in the obese is more benign. This is important, since obesity predisposes to hypertension and most who have hypertension are obese. This report examines the hypothesis for CVD outcomes considered by previous reports and also the subcategories of CVD disease such as myocardial infarction and stroke, and includes data on both men and women and on young and old. PMID- 2239673 TI - Clinical factors associated with delay time in suspected acute myocardial infarction. PMID- 2239674 TI - Iatrogenic left coronary artery fistula-to-left ventricle following PTCA: a previously unreported complication with nonsurgical management. PMID- 2239675 TI - Dehiscence of the proximal anastomosis of aortocoronary bypass graft. PMID- 2239676 TI - Idiopathic multiple left ventricular aneurysms. PMID- 2239677 TI - Aortic pseudoaneurysm occurring after cardiac transplantation. PMID- 2239678 TI - Right atrial myxoma causing total destruction of the tricuspid valve leaflets. PMID- 2239679 TI - Two-dimensional echocardiography and magnetic resonance imaging in diagnosis of idiopathic dilation of the right atrium. PMID- 2239680 TI - Acquired left ventricular-right atrial and right ventricular communication due to infective endocarditis after aortic valve replacement. PMID- 2239682 TI - Echocardiographic diagnosis of pulmonary embolus. PMID- 2239681 TI - Balloon dilatation of double-chamber right ventricle. PMID- 2239683 TI - Acutely blocked Blalock-Taussig shunt following cardiac catheterization: successful recanalization with intravenous streptokinase. PMID- 2239684 TI - Clinically undetected cardiac lymphoma causing fatal congestive heart failure. PMID- 2239685 TI - Common-type atrial flutter exhibiting double potential with phenomenon of entrainment assessed. PMID- 2239687 TI - The future of pharmacy: pharmaceutical care. PMID- 2239686 TI - Congenital coronary artery fistula: diagnosis by two-dimensional Doppler echocardiography. PMID- 2239688 TI - Georgia consumers' awareness and perceptions of generic drugs after the scandals. PMID- 2239689 TI - Give patients their Rx rights! PMID- 2239690 TI - Tapping employee insights with the Nominal Group Technique. AB - In our scenario, we brought together the manager, pharmacist, full-time and part time sales people, the delivery person, and the stock person, to give a perspective from every possible area of operation. We have found that input from all employees often generates ideas that they would not have thought of on their own. We suggest that NGT, used on a quarterly basis, for instance, would be an excellent means of developing team spirit, employee participation, and meaningful and effective solutions to problems. NGT is much better than trying to "go it alone," especially in today's competitive environment. NGT helps us realize that the potential contribution of employees is great, but generally untapped. The process requires planning but little time; yet it can produce astounding results, both in encouraging team spirit and in protecting profitability. The process fosters effective use of a participative style of management. It forces us, in effect, to use our most valuable resource: the people we manage. PMID- 2239691 TI - Phenylpropanolamine hydrochloride. AB - Phenylpropanolamine has been classified by the FDA advisory review panel as generally safe and effective for short-term weight control. The maximum daily dose for this indication is 75 mg. When used in recommended doses by patients without significant risk factors, serious side effects appear to occur infrequently. The pharmacist has an important role in preventing misuse and abuse of phenylpropanolamine through counseling the patient about its appropriate, short-term (not exceeding 12 weeks) use in a comprehensive weight-reduction program. Patients should be alerted to signs and symptoms of serious adverse reactions and advised to discontinue use if any reactions appear. PMID- 2239693 TI - Pharmaceutical care and the elderly. PMID- 2239692 TI - Overview of infectious diseases, Part 1. AB - Microbiologic characteristics include virulence, inoculum size, and the interplay between normal flora and pathogenic organisms. These characteristics, as well as relevant host factors, are an important part of the infectious disease process. Parts 2 and 3 of this series will review the use of drug therapy and the general manifestations of infectious diseases. PMID- 2239694 TI - Experimental contrast-associated nephropathy and its clinical implications. AB - Acute renal failure after contrast media injection has been recognized for at least 35 years but the exact mechanism responsible for the renal injury remains an enigma. The clinical characteristics of contrast-induced nephropathy (CAN) are well-known although more recently the nonoliguric presentation has occurred at an increased frequency--in 70 to 90% of cases. For nonoliguric presentation of CAN, one can expect an asymptomatic increase in serum creatinine, the mean peak occurring at 4.2 days. If oliguric, the fractional excretion of sodium will be less than 1% and resistant to either fluid challenge or loop diuretics. Preexisting renal insufficiency, with or without diabetes mellitus, increases the risk of CAN 6- to 10-fold but recovery is expected, with less than 10% of all patients requiring dialytic support. Despite the growing body of published reports, the lack of a suitable animal model to evaluate various proposed mechanisms of renal injury has compromised our ability to devise a technique for preventing CAN. A popular scheme has been proposed to describe the possible sequence by which ischemia or nephrotoxins, or both, induce acute renal failure. In particular, a vascular mechanism (i.e., ischemia), is an appealing explanation for CAN since acute changes in renal hemodynamics after contrast media injection have been confirmed by several animal experiments. Unlike other vascular beds in which contrast media induce acute vasoconstriction followed by vasodilatation, the initial effect on the renal circulation is acute vasodilatation, followed by progressive vasoconstriction, increasing renal vascular resistance and a concomitant decrease in both renal blood flow and glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239695 TI - Contrast media: the relation of chemical structure, animal toxicity and adverse clinical effects. AB - Chemotoxicity and osmotoxicity of contrast media (CM) are determined by chemical structure. The lower the chemotoxicity and osmotoxicity of the CM, the less animal toxicity and higher clinical tolerance in humans will be achieved. Nonionic monomers such as iohexol and iopamidol in iodine-equivalent concentrations have approximately half the osmolality and therefore half the osmotoxicity of ionic monomers such as diatrizoate, iodamide, iothalamate and metrizoate. Absence of carboxyl groups in nonionic CM, as opposed to the presence of carboxyl groups in ionic CM, results in a lower chemotoxicity in nonionic CM. Similarly, a larger number of hydroxyl groups in nonionic CM than in ionic CM result in a lower chemotoxicity. The lower chemotoxicity of nonionic CM is reflected as a higher subarachnoid and intravenous tolerance both in animals and in the clinical setting. PMID- 2239696 TI - A hematologist's view of contrast media, clotting in angiography syringes and thrombosis during coronary angiography. AB - While ionic contrast media (CM) are stronger anticoagulants and antiplatelet agents, both nonionic and ionic CM retard clotting, fibrinopeptide A generation and platelet aggregation (at least by Born-O'Brien aggregometry). Thus, nonionic CM do not cause clots and thrombi. Rather, the driving force for clot or thrombus formation, when it occurs, is blood contact with and activation by the foreign surface of a syringe or catheter itself. A marked enhancement of clotting by glass syringes in comparison to plastic ones supports this view. Blood in any syringe or catheter, therefore, will clot more slowly in the presence of nonionic or ionic CM, the inhibitory effects of the latter being more profound. With respect to models of thrombosis at sites of vascular injury or stenosis, the antithrombotic effects of CM may either be transient owing to the dynamic nature of blood flow (local endothelial cell denudation model), or as in the case of ionic CM, actually to enhance local platelet aggregation (stenosis model). In these situations, preservation of the antithrombotic functions of endothelium with nonionic CM may be quite critical. PMID- 2239697 TI - Selection of a contrast agent in the cardiac catheterization laboratory. AB - The evolution of contrast material for intravascular use has been directed toward the development of better-tolerated agents. Currently, a variety of such "dyes" are available for coronary angiography and left ventriculography. Considerable animal and human investigation suggests that significant differences exist between the families of contrast agents that relate to patient tolerance. The newer low osmolality agents (especially the nonionic agents) produce less perturbation of the homeostatic state, which is clinically manifested by a lessened incidence of side effects, including those of a hemodynamic and electrophysiologic nature. While controversy continues over the cost/benefit ratio of the low osmolality contrast agents compared to traditional high osmolality agents, the former are rapidly becoming the community standard for diagnostic and especially therapeutic cardiologic procedures. Accepting the advantages of the low osmolality contrast agents, differences between the ionic dimers and the nonionic agents have been examined. Both experimental and clinical data suggest superiority of the nonionic agents. Although controversy still surrounds the issue of thromboembolism with the nonionic agents, accumulating evidence fails to support a clinically significant relation. The choice of contrast material is the responsibility of the invasive cardiologist. While the benefits of low osmolality agents are most obvious in high-risk patients, experience with large-scale intravenous studies suggests that the choice of contrast agent is a better discriminator of adverse reaction than is preprocedural risk stratification. PMID- 2239698 TI - Contrast media safety: what do we know and how do we know it? AB - Use of an intravenous injection of a water-soluble iodine compound (sodium iodide) for visualizing the urinary tract was first described by Osborne in 1923. However, sodium iodide was accompanied by a high incidence of side effects and the image quality was not good. As newer, improved contrast agents were introduced, a number of investigators reported on the incidence of death and side effects incurred by their use. In 1975, the first large-scale, multicenter, prospective study on the incidence of fatal and nonfatal reactions was reported by Shehadi. In this series, the overall incidence of adverse reactions was 5.65%, of which 3.77% were mild, 1.77% were moderate, 0.02% were severe, and 0.0007% were fatal. Shehadi also noted that a history of allergy doubled the risk of adverse reaction and a history of a previous adverse reaction to contrast material trebled the risk; also, the risk of a reaction to an intraarterial injection was half that of the risk associated with an intravenous injection. With the introduction of low osmolar nonionic agents, other large-scale studies were performed because these agents appeared to cause significantly fewer adverse reactions. However, they were from 10 to 15 times more expensive than their predecessors. In 1987, Lasser reported on the increased safety of ionic agents when patients were pretreated with steroids. Palmer in Australia and Katayama in Japan collected 120,000 and 335,000 patients, respectively, and compared the incidence of adverse reactions of the ionic versus the nonionic agents. Wolf recently reported a study that included a direct comparison of ionic agents with pretreatment with steroids versus nonionic agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239699 TI - The cardiac catheterization laboratory--1990. AB - Over the past several decades, there has been an evolution and proliferation of catheterization laboratories. During the latter half of the 1980s, these changes have resulted from the development of a number of catheter-based therapeutic techniques. In general, it would seem reasonable to predict that the 1990s will continue to show expansion of laboratory services in both traditional hospital and nontraditional settings. In the latter, the free-standing laboratories will probably grow substantially. The types of patients studied in this new era will continue to be largely those with suspected or known coronary artery disease. The most dramatic changes in laboratory configuration will be in the image system. High-definition systems will become the standard. Images will be recorded direct to solid-state memory using fluoroscopic techniques. Resolution will be increased at reduced noise and enhanced contrast. Higher resolution video monitors and video recorders will be the cornerstones of the laboratory. The image information for an entire day's work will be stored first on a digital tape system, probably a rapidly accessed reel system, and by the late 1990s in solid-state memory. Individual case data will then be copied to smaller cassettes for patient reports. An entirely digital system will provide rapid electronic acquisition, processing, storage and transmission of information. In addition, physicians will be able to call up previous studies that have been copied to this format for storage. Storage space will be reduced considerably. Access of information will be relatively rapid compared with cine equipment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239700 TI - Clinical cardiovascular magnetic resonance imaging. AB - Magnetic resonance imaging (MRI) is a powerful tool providing high-resolution images of the heart and great vessels without the use of ionizing radiation or contrast agents. MRI systems currently in use at many hospitals can be used effectively in the routine, clinical evaluation of many forms of cardiovascular disease, including great vessel disease, ischemic cardiac disease and congenital cardiac disease. Moreover, quantitative and cine MRI techniques are now available, which provide highly accurate measures of chamber size, wall motion and wall thickening. Recent developments in the areas of myocardial tagging, high speed imaging and MR assessments of flow and perfusion suggest potential for an increasing role of MRI in the clinical evaluation of the cardiovascular system. PMID- 2239701 TI - Clinical nuclear magnetic resonance spectroscopy: insight into metabolism. AB - Nuclear magnetic resonance (NMR) spectroscopy can nondestructively evaluate changes in metabolites with different disease states, as well as with therapeutic interventions. Animal studies have provided the basis for understanding changes in high-energy phosphates with myocardial ischemia. Studies of graded ischemia due to partial coronary stenosis have shown the sensitivity of the ratio of phosphocreatinine to inorganic phosphate to small reductions in myocardial blood flow and its relation to myocardial function. The application of NMR spectroscopy to humans requires precise localization techniques to avoid acquiring contaminating information from structures around the heart, such as the chest wall and diaphragm. With these localization techniques, metabolic evidence of ischemia has been demonstrated in patients with myocardial infarction and patients with known coronary disease, although the sensitivity of this technique for the diagnosis of inducible ischemia is unknown. At rest, patients with dilated and hypertrophic cardiomyopathies often have an elevated phosphodiester resonance, possibly signifying abnormal breakdown of membrane phospholipids. Increasing oxygen demand in these patients does not usually alter high-energy phosphates, suggesting that oxidative energy metabolism is preserved under these conditions. NMR spectroscopy is a powerful tool to increase understanding of metabolic changes in a variety of pathologic conditions. PMID- 2239703 TI - Role of magnetic resonance contrast agents in cardiac imaging. AB - Improvements in magnetic resonance imaging (MRI) technology allow adequate spatial and temporal resolution to capture cardiac anatomy and contractile function in exceptional detail and with little risk. However, tissue characterization of the pathophysiologic state of the myocardium may require special indicators or MR contrast agents. These must be tailored for detection by the MRI process, but available agents are effective at low dose and provide a wide range of indicator properties (e.g., myocardial extracellular space, blood pool, capillary permeability and membrane transport). Each agent has a dynamic washin and washout time-intensity curve that may reflect myocardial perfusion or consequences of ischemia. The combined use of MRI and MR contrast agents may provide a single diagnostic examination that fully and quantitatively assesses all indexes of cardiac performance. Such information would be both global and regional, and would be well tolerated by patients. The cost, value and cost effectiveness of such studies remain speculative. PMID- 2239702 TI - Positron emission tomography and interventional cardiology. AB - Current noninvasive diagnostic techniques have limited accuracy for detection of coronary artery disease (CAD) in symptomatic and (particularly) asymptomatic patients with silent disease. Furthermore, no standard noninvasive method provides reliable diagnostic information on the location of the coronary arteries involved, the severity of stenosis, the presence of collaterals and myocardial viability. Based on greater than 1,000 cardiac studies at the University of Texas, cardiac positron emission tomography (PET) with either generator-produced rubidium-82, cyclotron-produced N-13 ammonia, or F-18 deoxyglucose is suitable for 4 routine diagnostic purposes: (1) noninvasive diagnosis of CAD in either symptomatic or asymptomatic subjects with a sensitivity of 95 to 98% and specificity of 95 to 100%. This accuracy is now sufficient to schedule diagnostic catheterization and multivessel angioplasty with surgical backup on the basis of the PET scan. At the University of Texas we carry out PET in asymptomatic and symptomatic patients to direct those with mild disease to cholesterol-lowering reversal therapy and those with severe disease to percutaneous transluminal coronary angioplasty (PTCA); (2) assessment of physiologic severity of coronary artery stenosis as compared to automated quantitative coronary arteriographic analysis. Changes in stenosis severity are followed before and after interventions including PTCA, bypass surgery, vasodilator drugs and cholesterol control regimens for reversal of coronary atherosclerosis; (3) imaging myocardial infarction, ischemia, viability, zone at risk and sizing of these pathophysiologic processes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239704 TI - Cardiovascular effects of iodinated contrast agents. AB - The ideal intravascular contrast agent would be biologically inert and have no pharmacologic actions. Pharmacologic actions of currently used radiographic contrast agents are determined principally by 3 physicochemical properties of the iodine-bearing molecule and its formulation: osmolality, sodium concentration and calcium-binding properties. Within this framework, the calcium-binding 1.5 ratio agents have the most marked effects, and the 3.0 ratio nonionic agents the least, with the noncalcium-binding formulations of 1.5 ratio agents and ioxaglate (the only 3.0 ratio ionic agent) in between. Differences in hemodynamic effects are predominantly related to osmolality with the 3.0 agents causing less hemodynamic disturbance. The magnitude of difference is small enough that the 3.0 ratio agents have no important clinical advantage when used in patients with good or moderately impaired left ventricular function. However, the difference may be important in patients with severely impaired circulatory performance. The principal electrophysiologic differences are between the calcium-binding 1.5 ratio agents (which are associated with a clear-cut greater frequency of ventricular fibrillation during coronary injection than the noncalcium-binding 1.5 ratio agents) and the 3.0 ratio agents. There is no justification for the use of calcium-binding 1.5 ratio agents, since noncalcium-binding formulations of the same molecule are available at the same price. The circulatory reserve of most patients makes the differences between 3.0 ratio agents and noncalcium-binding 1.5 ratio agents clinically unimportant. In view of the substantial price disparity between 1.5 ratio and 3.0 ratio agents, noncalcium-binding 1.5 ratio agents are appropriate for patients with good circulatory performance and 3.0 ratio agents are best reserved for patients with impaired circulatory performance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239705 TI - A symposium: triggering and circadian variation of onset of acute cardiovascular disease. Introduction. PMID- 2239706 TI - Epidemiologic studies demonstrating increased morning incidence of sudden cardiac death. AB - To determine if sudden cardiac death shows a circadian variation, the mortality records of the Massachusetts population and the Framingham Heart Study were analyzed. The Massachusetts mortality data analysis revealed an increased morning incidence for out-of-hospital cardiac deaths similar to that previously described for nonfatal myocardial infarction. The records of the Framingham Heart Study allowed more comprehensive analysis of the time of sudden cardiac death. In this study, a prominent circadian variation was also identified in which frequency of sudden cardiac death increased sharply between 6 A.M. and 9 P.M.; distribution was fairly even throughout the rest of the day. This circadian pattern may be explained in part by physiologic changes that increase the likelihood of ventricular fibrillation or increase the risk of thrombosis in the morning hours. The possible role of the morning increase in physical and mental activity as a trigger of sudden cardiac death requires further investigation. PMID- 2239707 TI - Timing and triggers of transient myocardial ischemia. AB - Use of exercise tolerance testing and new techniques of ambulatory electrocardiographic monitoring to more objectively measure myocardial ischemia have enabled clinicians to better recognize the magnitude, timing and variable characteristics of transient ischemic events. These commonly occurring events in patients with coronary artery disease have a diurnal pattern strikingly similar to that reported for catastrophic cardiovascular events such as myocardial infarction, sudden cardiac death and stroke. Whether those factors that contribute to reversible ischemic events are similar to those causing infarction and sudden death has not been resolved. However, the parallel increase in morning activity for these related phenomena suggests that a better understanding of the triggers of reversible myocardial ischemia may help improve understanding of the causes of myocardial infarction and sudden cardiac death. PMID- 2239708 TI - Application of time series analysis to circadian rhythms: effect of beta adrenergic blockade upon heart rate and transient myocardial ischemia. AB - Circadian variations of transient myocardial ischemia and heart rate have been identified, but the rhythms and their response to beta blockade have not been fully characterized. Time-series analysis, a mathematical technique to describe oscillatory activity occurring within a continuous data set was used, to address these issues. Nine men with coronary artery disease underwent 72 hours of ambulatory electrocardiographic monitoring during therapy with placebo or metoprolol. During administration of placebo, ischemic time and heart rate showed a primary peak with a periodicity of approximately 24 hours with a tight coupling between the 2 variables and a secondary peak with a periodicity of 5 to 8 hours. During metoprolol therapy, heart rate and ischemic variation were reduced and the 24-hour periodicity for heart rate only remained. The 24-hour periodicity for ischemia was eliminated, but the data with 5- to 8-hour periodicity became the major component of the signal. PMID- 2239709 TI - Transient myocardial ischemia and its relation to determinants of myocardial oxygen demand. AB - Because of conflicting data and a clear need to establish the relative role of increase in myocardial oxygen demand versus reduction in coronary blood flow in the causation of transient ischemia, the role of heart rate and blood pressure changes immediately preceding and during the transient ischemic events observed during daily life were evaluated in 25 patients with coronary artery disease. Elevations in heart rate before onset of ischemia were observed in 61% of the episodes. Similarly, 73% of the ischemic events were preceded by an increase in arterial pressure. These data provide evidence for a significant role of increased myocardial oxygen demand in the genesis of transient myocardial ischemia. PMID- 2239710 TI - Mental stress as an acute trigger of ischemic left ventricular dysfunction and blood pressure elevation in coronary artery disease. AB - Acute mental stress may be a frequent trigger of transient myocardial ischemia, myocardial infarction and sudden cardiac death. In an experimental setting, the effect of mental stress on hemodynamics and left ventricular wall motion abnormalities (as detected by radionuclide ventriculography) was measured in 29 patients with exercise-induced myocardial ischemia. Seventy-five percent of the patients demonstrated mental stress-induced wall motion abnormalities. Patients frequently exhibited greater increases in peak systolic arterial pressure during mental stress than during exercise. Personally relevant mental stress is the most potent type of mental stress, both in terms of frequency and magnitude of ischemia. Most mental stress-induced ischemic episodes are clinically and electrocardiographically silent and occur at heart rates significantly lower than those seen during exercise. Both systolic and diastolic blood pressure increased during mental stress-induced ischemia, suggesting that increased myocardial oxygen demand plays a role in the pathophysiology of mental stress-induced transient ischemia. The significant magnitude and acute onset of this mental stress-induced blood pressure elevation may in some manner contribute to atherosclerotic plaque rupture. These findings may provide a pathophysiologic link to the epidemiologic association between mental stress and acute ischemic coronary events. A new ambulatory radionuclide detector that can concurrently monitor left ventricular ejection fraction and electrocardiographic ST-segment change may enhance the detection and evaluation of transient myocardial ischemia in ambulatory coronary patients. PMID- 2239711 TI - Triggers of transient myocardial ischemia: circadian variation and relation to plaque rupture and coronary thrombosis in stable coronary artery disease. AB - The phenomenon of transient myocardial ischemia is common in patients with stable coronary disease and appears to be due both to increases in myocardial demand and to episodic coronary vasoconstriction. The circadian variation of transient ischemic episodes closely parallels the circadian variation of acute coronary syndromes associated with plaque rupture, such as myocardial infarction and sudden death. These concordant temporal patterns of transient ischemia, myocardial infarction and sudden cardiac death probably represent independent manifestations stemming from the consequences of increased sympathetic activity. PMID- 2239712 TI - Cause of thrombosis in human atherosclerotic arteries. AB - Although it has been known for a long time that thrombosis nearly always develops in atherosclerotic arteries--and almost never in normal vessels--the mechanism through which atherosclerosis promotes thrombosis was unknown until this problem was explored through histologic examination of complete serial section sets of thrombosed atherosclerotic arteries. These studies, repeatedly confirmed, revealed that the thrombi are triggered by microscopic cracks in the collagen cap of advanced plaques. Blood most often seeps from the arterial lumen through the cracks into the underlying lipid gruel before the breaks or cracks are plugged by the thrombi (which function as hemostatic seals of the breaks). These results are parallel to results of experimental studies in which the synergism of endotheliotoxic and pressor agents produced thrombi over cap breaks and sub-break hemorrhages only in arteries with advanced collagen-rich plaques, not in arteries with early atherosclerosis or in normal vessels. This finding indicates that advanced atherosclerosis makes the arterial wall much more fragile and that, once broken, this wall exposes the blood to powerful thrombogenic materials that do not exist in normal arterial tissue. At present, human and experimental evidence suggest that the thrombogenic fissures of advanced plaque caps can be promoted by several factors, such as a surge in intraarterial pressure or insults that damage the caps structurally and increase their vulnerability to any type of stress such as certain metabolic, exogenous chemical and immune insults, spontaneous molecular changes of collagen with time and hemorrhages of capillaries that invade advanced plaques from the adventitia or the arterial lumen. PMID- 2239713 TI - Rupture of coronary vasa vasorum as a trigger of acute myocardial infarction. AB - Some controversy has always existed regarding the presence and extent of the vasa vasorum--the nutrient vessels in the wall of the human aorta--in the coronary arteries. Now, cinemicrographic studies using silicone polymer injections in cleared human hearts have identified the vasa vasorum of coronary arteries, revealing evidence of neovascularization in the region of atherosclerotic plaques. These studies suggest an important role for the vasa vasorum in the pathogenesis of coronary atherosclerosis and its sequelae, especially intramural hemorrhage and vascular spasm. The wall of the human coronary artery in regions of atherosclerotic injury may be particularly rich in capillary vessels of the vasa vasorum. From this, the evidence suggests that with the morning increase in blood pressure, fragile neovascular structures of the vasa vasorum may be more prone to rupture and may be responsible, in part, for the circadian variation in myocardial infarction. PMID- 2239714 TI - Angiographic assessment of the culprit coronary artery lesion before acute myocardial infarction. AB - Serial angiographic studies of patients with myocardial infarction and unstable angina suggest that the culprit plaque underlying a thrombus need not have produced severe luminal obstruction before onset of the event. An atherosclerotic coronary artery lesion can, therefore, have 2 important characteristics. First, it may be obstructive. Second, it may be "vulnerable" in that it has the potential to become thrombogenic if exposed to the appropriate triggering stimulus. A lesion need not be obstructive to become thrombogenic, nor do all obstructive lesions have thrombogenic potential. The cause of an infarction may thus be rupture of a nonobstructive plaque leading to occlusive thrombus formation. Because it may be difficult to predict the site of a subsequent occlusion from a coronary angiogram, coronary bypass surgery or angioplasty directed only at discernible stenotic lesions may not be effective for preventing subsequent myocardial infarctions. Appropriate therapy may need to be directed at the entire coronary tree. Such therapy might include cholesterol lowering, beta blockade and aspirin. PMID- 2239715 TI - Propranolol and the morning increase in sudden cardiac death: (the beta-blocker heart attack trial experience). AB - To provide insight into the protective effect of propranolol on mortality after myocardial infarction observed in the beta-Blocker Heart Attack Trial, the time of occurrence of sudden cardiac death was examined in this population. Between 5 A.M. and 11 A.M., 25 of the 56 total deaths (38%) occurred in the placebo patients compared with 11 of 45 (24%) in the propranolol patients. Excluding this period, there were nearly equal numbers of sudden cardiac deaths in the propranolol and placebo groups. This retrospective analysis suggests that beta blockade is protective during the morning hours when a surge of sympathetic activity may increase the risk of sudden cardiac death. PMID- 2239716 TI - Exercise test predictors of ambulatory silent ischemia during daily life in stable angina pectoris. AB - The predictive value of several exercise test parameters in identifying stable angina patients at risk of silent myocardial ischemia during daily life were examined. A total of 97 patients with coronary artery disease, stable angina and ambulatory electrocardiographic data were evaluated. Of the 86 patients with a positive exercise test, 39 (group 1) had greater than or equal to 1 episodes of ST-segment depression and 47 (group 2) did not develop ST changes during ambulatory electrocardiographic monitoring. Comparison of the exercise test parameters between the 2 groups revealed early onset of ischemia during exercise tests as the single most significant (p less than 0.0005) predictor of ambulatory silent ischemia. The other exercise test parameters showing significant differences between the 2 groups were the peak exercise heart rate (117 +/- 23 vs 126 +/- 20 beats/min, p less than 0.05) and peak systolic blood pressure (160 +/- 27 vs 176 +/- 27 mm Hg, p less than 0.01), both of which were significantly lower in the group 1 patients. These data were used to derive simple mathematical formulas for calculating the risk of ambulatory silent ischemia. These results demonstrate that stable angina patients at risk of silent ischemia during daily life can be accurately identified by evaluation of selected exercise test parameters. PMID- 2239717 TI - Effects of theophylline, atenolol and their combination on myocardial ischemia in stable angina pectoris. AB - The effects of theophylline (400 mg twice a day), atenolol (50 mg twice a day) and their combination on myocardial ischemia were studied in 9 patients with stable angina pectoris in a randomized, single-blind, triple crossover trial. Placebo was administered to the patients during the run-in and the run-off periods. A treadmill exercise test and 24-hour ambulatory electrocardiographic monitoring were obtained at the end of each treatment period. Compared with placebo, theophylline significantly improved the time to onset of myocardial ischemia (1 mm of ST-segment depression) from 7.8 +/- 3.7 to 9.5 +/- 3.7 minutes (p less than 0.03) and the exercise duration from 9 +/- 3.4 to 10.1 +/- 3.5 minutes (p less than 0.04). During atenolol and during combination treatment, the time to the onset of ischemia and the exercise duration were similar (10.8 +/- 4.2 and 11.2 +/- 3.2 minutes, 11.2 +/- 3.6 and 11.5 +/- 3.2 minutes, respectively) and longer than during theophylline administration (p less than 0.05). Ambulatory electrocardiographic monitoring showed that, during theophylline administration, the heart rate was higher than during placebo throughout the 24 hours (p less than 0.05). During atenolol and during combination treatment the heart rate was similar and in both cases lower than during placebo (p less than 0.05). Compared with placebo, theophylline decreased the total ischemic time from 97 +/- 110 to 70 +/- 103 minutes (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239718 TI - Transient left ventricular cavitary dilation during dipyridamole-thallium imaging as an indicator of severe coronary artery disease. AB - Transient left ventricular (LV) cavitary dilation during dipyridamole-thallium imaging was reported in 45 of 510 (9%) consecutive patients referred for dipyridamole-thallium imaging. Clinical and hemodynamic effects observed during dipyridamole infusion were not predictive of transient cavitary dilation on the thallium images. Coronary angiography was performed in 32 of the 45 patients: 75% had either left main, 3-vessel or "high-risk" 2-vessel coronary artery disease. Although 25 of 45 patients (56%) with transient cavitary dilation were either asymptomatic or had only grade 1/4 effort angina, 16 of 25 patients (64%) not referred for coronary revascularization sustained a cardiac event during a mean follow-up of 12 months. Most events were cardiac deaths (75%) and 87% of events occurred within 4 months of the test. Noncardiac surgery was performed in 187 of the 510 patients. The postoperative cardiac event rate was 2% in the 101 patients with normal scans or fixed defects, 19% in 75 patients with reversible perfusion defects and 58% in 12 patients with reversible cavitary dilation (p less than 0.0001). Thus, transient LV dilation during dipyridamole-thallium imaging is a marker of severe underlying coronary artery disease, denotes a poor prognosis and predicts a high risk of postoperative cardiac complications in patients who undergo noncardiac surgery. PMID- 2239720 TI - Videodensitometry versus digital calipers for quantitative coronary angiography. AB - Single-plane left coronary angiograms in 18 patients were prospectively analyzed using videodensitometry (XR-70 system) and handheld digital calipers to compare arterial dimensions, stenosis dimensions, intraobserver variability and interobserver variability for the methods. A total of 648 arterial segments were measured, yielding a highly significant correlation between videodensitometry and caliper-determined cross-sectional area (r = 0.96, p = 0.0001). Similarly, a highly significant linear relation was observed between videodensitometry and caliper-determined diameter (r = 0.95, p = 0.0001). When data subsets for small, medium and large arterial segments were examined, higher variability in the correlation between videodensitometry and caliper-determined area was observed in the large segments (greater than 10 mm2). In addition, caliper-estimated areas tended to be slightly smaller than videodensitometry-estimated areas in these segments. For diameter estimations, correlations between caliper and videodensitometry data were similar for the entire range of arterial segment sizes. Intra- and interobserver variability was low for both caliper and videodensitometry determination of diameter or area. Thus, over a wide range of arterial dimensions, results obtained with caliper estimates of luminal area and diameter are comparable to those obtained with videodensitometry using the XR-70 system. PMID- 2239719 TI - Effects of two types of fish oil supplements on serum lipids and plasma phospholipid fatty acids in coronary artery disease. AB - Fish oil has consistently been shown to lower triglyceride levels, but its effects on low-density lipoprotein (LDL) cholesterol remain controversial. The current study compares the long-term effects of 2 different fish oil preparations (ethyl ester and triglyceride) versus olive oil in patients with coronary artery disease. Eighty-nine subjects were randomly assigned to receive capsules containing 6 g/day (triglyceride group) or 7 g/day (ethyl ester group) of n-3 fatty acids, or capsules containing 12 g/day of olive oil for 6 months. Mean triglyceride levels decreased by 28% in the ester and 32% in the triglyceride fish oil groups (p less than 0.05 for both). LDL cholesterol levels increased by 3% (difference not significant) in the ester and 12% (p less than 0.05) in the triglyceride fish oil groups; in hypertriglyceridemic subjects the increase was 23% (p less than 0.01) and 14% (difference not significant), respectively. Plasma phospholipid fatty acid analysis showed a fivefold increase in eicosapentaenoic acid levels in both fish oil groups (p less than 0.001), and a long-term decrease in arachidonic acid levels (p less than 0.001). Achieved eicosapentaenoic acid level correlated with the degree of increase in LDL cholesterol (r = 0.38, p less than 0.05). These data suggest that fish oil administration is associated with an increase in LDL cholesterol levels in a diverse group of patients with coronary artery disease; this change appears to be correlated with n-3 fatty acid absorption. The impact of this increase in LDL is unknown, but should be considered as potentially adverse. PMID- 2239721 TI - Frequency of myocardial indium-111 antimyosin uptake after uncomplicated coronary artery bypass grafting. AB - The reported incidence of myocardial damage after coronary artery bypass grafting (CABG) is highly related to the methods used. Since indium-111 monoclonal antimyosin antibody scintigraphy has been shown to be highly specific and sensitive for myocardial necrosis, even in small lesions, uptake of this radiotracer was evaluated after CABG. In 23 consecutive patients without previous myocardial infarction who underwent CABG for stable angina, 80 MBq indium-111 antimyosin was injected on the third postoperative day. Planar images were obtained 48 hours later and analyzed for myocardial uptake of indium-111 antimyosin. Scintigraphic results were related to creatine kinase MB levels, duration of both aortic cross-clamping and cardiopulmonary bypass, and electrocardiographic changes. In all patients surgical procedure and postoperative course was uncomplicated. Indium-111 antimyosin uptake was present in 19 of 23 patients (82%). It was diffused in 7 patients and localized in 12. No pathologic Q waves occurred postoperatively. Fourteen patients exhibited ST segment changes. No good relation was found among indium-111 antimyosin uptake and creatine kinase MB levels, duration of cross-clamping or bypass, and ST-T changes. It is concluded that some degree of myocardial damage, though silent, is common after CABG. PMID- 2239722 TI - Time course and prognostic significance of serial signal-averaged electrocardiograms after a first acute myocardial infarction. AB - The prognostic significance of serial signal-averaged electrocardiograms recorded during the first 3 days (period 1), in the second week (period 2) after a first acute myocardial infarction (AMI) and 6 months later (period 3) was prospectively assessed in 190 patients. No patients were treated with thrombolytic therapy. Patients with conduction disturbances were excluded. Mean age of the 190 patients was 57 years (range 34 to 74) and mean left ventricular ejection fraction was 40 + 6% (range 12 to 70). Eighty-four patients had an anterior wall AMI and the remaining 106 patients an inferior wall AMI. After a mean follow-up of 24 months, 16 patients developed sustained symptomatic monomorphic ventricular tachycardia, 7 patients were resuscitated from an episode of ventricular fibrillation, and 10 patients died suddenly. Multivariate regression analysis using continuous variables showed that the strongest predictor of sustained ventricular tachycardia and ventricular fibrillation was the left ventricular ejection fraction (p less than 0.0001) followed by the duration of QRS complex on the signal-averaged electrocardiogram recorded during the first 3 days of AMI (p less than 0.0005). Sudden death was only predicted by left ventricular ejection fraction (p less than 0.02). PMID- 2239723 TI - Prognostic value of predischarge low-level exercise thallium testing after thrombolytic treatment of acute myocardial infarction. AB - Low-level exercise thallium testing is useful in identifying the high-risk patient after acute myocardial infarction (AMI). To determine whether this use also applies to patients after thrombolytic treatment of AMI, 64 patients who underwent early thrombolytic therapy for AMI and 107 patients without acute intervention were evaluated. The ability of both the electrocardiogram and thallium tests to predict future events was compared in both groups. After a mean follow-up of 374 days, there were 25 and 32% of cardiac events in the 2 groups, respectively, with versus without acute intervention. These included death, another AMI, coronary artery bypass grafting or angioplasty with 75% of the events occurring in the 3 months after the first infarction. The only significant predictors of outcome were left ventricular cavity dilatation in the intervention group and ST-segment depression and increased lung uptake in the nonintervention group. The sensitivity of exercise thallium was 55% in the intervention group and 81% in the nonintervention group (p less than 0.05). Therefore, in patients having thrombolytic therapy for AMI, nearly half the events after discharge are not predicted by predischarge low-level exercise thallium testing. The relatively weak correlation of outcome with unmasking ischemia in the laboratory before discharge may be due to an unstable coronary lesion or rapid progression of disease after the test. Tests considered useful for prognostication after AMI may not necessarily have a similar value if there has been an acute intervention, such as thrombolytic therapy. PMID- 2239724 TI - Prognosis of acute myocardial infarction complicated by primary ventricular fibrillation. Principal Investigators of the SPRINT Study. AB - In 5,839 consecutive patients with acute myocardial infarction (AMI), hospitalized between July 1981 and July 1983 in 14 coronary care units in Israel, the incidence of primary ventricular fibrillation (VF) was 2.1%. Patients with primary VF resembled counterparts without VF in terms of age, gender, frequency of previous AMI and past cigarette smoking habits. The hospital course of patients with primary VF revealed increased incidence of primary atrial fibrillation and atrioventricular block. Increased serum levels of glutamic oxaloacetic transaminase and lactic dehydrogenase were noted among the patients with primary VF. In-hospital mortality rate was 18.8% in 122 patients with primary VF compared with 8.5% in 3,707 patients forming the reference group (p less than 0.01). Adjustment by age using logistic function yielded an estimate of 2.86 for relative mortality odds associated with primary VF, and further adjustment by gender, history of AMI, systemic hypertension, and by enzymatically estimated infarct size slightly reduced the estimated odds, at 2.52 (95% confidence interval, 1.42 to 4.46). Prognosis after discharge from the hospital was independent of primary VF. In conclusion, primary VF exerts an independent, significant effect on in-hospital mortality. PMID- 2239725 TI - Usefulness of labetalol in chronic atrial fibrillation. AB - Beta-adrenergic blocking agents are useful in controlling excessive ventricular rate in chronic atrial fibrillation (AF) but often reduce exercise capacity. To investigate the advantage of labetalol--a unique beta blocker with alpha-blocking property--in chronic AF, 10 patients without underlying structural heart disease were studied with treadmill test, 12-minute walk and 24-hour ambulatory electrocardiographic monitoring. Patients were randomized and crossed over to receive 4 phases of treatment (placebo, digoxin, digoxin with half-dose labetalol, and full-dose labetalol). Exercise durations were 14.1 +/- 1.5, 14.2 +/- 1.5, 16.1 +/- 1.1 and 15.6 +/- 1.1 minutes, respectively, indicating that labetalol did not reduce exercise tolerance. Although digoxin had no advantage over placebo in controlling maximal heart rate (177 +/- 2 vs 175 +/- 3 beats/min), labetalol, both as monotherapy or as an adjunct to digoxin, was advantageous (156 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, and 154 +/- 4 vs 177 +/- 2 beats/min, p less than 0.01, respectively). The rate-pressure product was consistently lowered by labetalol at rest and during exercise. At peak exercise, the addition of labetalol to digoxin reduced the maximal rate pressure product achieved from 30,900 +/- 1300 to 24,100 +/- 2,000 mm Hg/min (p less than 0.01) and the maximal rate-pressure product was lowest with full-dose labetalol (22,300 +/- 1,600 mm Hg/min). During submaximal exercise on treadmill or during the 12-minute walk, the combination of labetalol and digoxin produced the best heart rate control, whereas labetalol monotherapy was comparable to digoxin therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239726 TI - Usefulness of combined propranolol and verapamil for evaluation of surgical ablation of accessory atrioventricular connections in patients without structural heart disease. AB - Successful surgical ablation of atrioventricular (AV) accessory connections may be confirmed during postoperative electrophysiologic testing by the absence of accessory connection conduction in both the anterograde and retrograde directions. Whereas the former may be readily apparent by examination of the surface electrocardiogram during sinus rhythm or atrial pacing, assessment of the latter may be complicated by the frequent presence of enhanced retrograde AV nodal conduction in the postoperative period. Consequently, availability of interventions that selectively affect AV nodal conduction and refractoriness without concomitant effects on accessory connections may be helpful for assessing the success of the surgical procedure. In this study the effects of combined propranolol and verapamil administration on electrophysiologic properties of the AV node and the accessory AV connection were assessed both pre- and postoperatively in 17 patients (12 men and 5 women, mean age 33 years) undergoing surgical ablation of accessory connections. Preoperatively, electrophysiologic characteristics of all but 1 of the accessory AV connections were unaffected by propranolol and verapamil administration. Postoperatively, on the other hand, propranolol and verapamil significantly prolonged both the retrograde AV node effective refractory period (baseline: 272 +/- 34 ms vs after drugs: 384 +/- 70 ms [p less than 0.0001]) and the shortest cycle length maintaining 1:1 ventriculoatrial conduction (baseline: 357 +/- 99 ms vs after drugs: 485 +/- 64 ms [p less than 0.0001]). Late postoperative electrophysiologic evaluation (7 +/- 3 weeks) revealed no evidence of residual accessory AV connection conduction, and all patients remain asymptomatic at 21 +/- 10 months follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239727 TI - Effectiveness of the once-daily calcium antagonist, lacidipine, in controlling 24 hour ambulatory blood pressure. AB - The efficacy of the new once-daily dihydropyridine calcium antagonist, lacidipine, in reducing ambulatory intraarterial blood pressure (BP) was examined in 12 untreated hypertensive patients. The intraarterial recording was commenced 24 hours before the first 4-mg dose and was continued for a further 24 hours thereafter. After dose titration and chronic therapy, a second 24-hour ambulatory BP recording was made. There was a steady onset of drug action, maximal at 2 hours, but with reflex tachycardia after the first dose. Chronic administration reduced BP throughout the 24-hour period, without tachycardia. Mean daytime reduction in BP was 20 mm Hg systolic (p less than 0.005) and 12 mm Hg diastolic (p less than 0.02). Mean nighttime reduction was 8-mm Hg systolic (p less than 0.05) and 6-mm Hg diastolic (difference not significant). There was no postural decrease in BP on 60 degrees head-up tilting and hypotensive action was maintained during isometric exercise (reduction at peak of 32/18 mm Hg, p less than 0.05) and throughout dynamic exercise (reduction at peak of 23/14 mm Hg, p less than 0.05). Lacidipine is an effective once-daily antihypertensive agent, with good control of stress response. PMID- 2239728 TI - Atenolol therapy for exercise-induced hypertension after aortic coarctation repair. AB - After successful repair of coarctation of the aorta in childhood, exercise induced upper body systolic hypertension is well documented. Beta blockade has been shown to reduce the arm/leg gradient in untreated coarctation of the aorta; treatment before coarctation repair has decreased paradoxical hypertension after repair. Ten patients with successful surgical repair of coarctation, defined as a resting arm/leg gradient of less than or equal to 18 mm Hg, were evaluated by treadmill exercise before and after beta blockade with atenolol. Mean age was 5.5 years at repair and 18 at study. At baseline evaluation, systolic blood pressures at termination of exercise ranged from 201 to 270 mm Hg (mean 229 mm Hg). Arm/leg gradients at exercise termination ranged from 30 to 143 mm Hg (mean 84). Follow up treadmill exercise studies were performed after beta blockade. Upper extremity systolic pressures at exercise termination were normalized in 9 of 10 patients. Maximal systolic blood pressure recorded at exercise termination ranged from 163 to 223 mm Hg (mean 196 mm Hg, p less than or equal to 0.005). Arm/leg gradient at termination of exercise also decreased significantly to a mean of 51 mm Hg (p less than 0.05). No patient had symptoms on atenolol and exercise endurance times were unchanged. The study results in this small series suggest that cardioselective beta blockade can be used to treat exercise-induced upper body hypertension effectively after surgical repair of coarctation. Because a high incidence of premature cardiovascular disease has been well documented after satisfactory surgical repair, the findings are of importance for this group of postoperative patients. PMID- 2239729 TI - Risk of cardiovascular mortality in alcohol drinkers, ex-drinkers and nondrinkers. AB - Lower cardiovascular mortality rates in lighter drinkers (versus abstainers or heavier drinkers) in population studies have been substantially due to lower coronary artery disease (CAD) mortality. Controversy about this U-shaped curve focuses on whether alcohol protects against CAD or, because of other traits, whether abstainers are at increased risk. Inclusion of ex-drinkers among abstainers in some studies has led to speculation that this might be the trait increasing the risk of abstainers. This new prospective study among 123,840 persons with 1,002 cardiovascular (600 CAD) deaths showed that ex-drinkers had higher cardiovascular and CAD mortality risks than lifelong abstainers in unadjusted analyses, but not in analyses adjusted for age, gender, race, body mass index, marital status and education. Use of alcohol was associated with higher risk of mortality from hypertension, hemorrhagic stroke and cardiomyopathy, but with lower risk from CAD, occlusive stroke and nonspecific cardiovascular syndromes. Subsets free of baseline cardiovascular or CAD risk had U-shaped alcohol-CAD curves similar to subsets with baseline risk. Among ex drinkers, maximal past intake and reasons for quitting (medical versus non medical) were unrelated to cardiovascular or CAD mortality. These data show that: (1) alcohol has disparate relations to cardiovascular conditions; (2) higher cardiovascular mortality rates among ex-drinkers are due to confounding traits related to past alcohol use; and (3) the U-shaped alcohol-CAD relation is not due to selective abstinence by persons at higher risk. The findings indirectly support a protective effect of lighter drinking against CAD. PMID- 2239730 TI - Subnormal parasympathetic activity after cardiac transplantation. AB - Heart period variability (standard deviation of 120 consecutive RR or PP intervals) was used to assess baseline parasympathetic activity in 18 patients with congestive heart failure before and after orthotopic cardiac transplantation, and was compared to that of 16 age-matched control subjects. Mean heart period variability (+/- standard error of the mean) was significantly greater (p less than 0.05) in control subjects (58 +/- 5 ms) than in the patients at any time before or after transplantation. Heart period variability of innervated recipient atria did not change significantly early (1 to 4 weeks) after transplantation (16 +/- 2 to 24 +/- 5 ms; p = 0.11), but increased significantly between weeks 15 and 37 after transplantation (30 +/- 5 ms, p less than 0.002 versus before transplantation). A stepwise regression model (R2 = 0.35; p = 0.01) showed that heart period variability was directly related to time after transplantation and inversely related to systolic arterial pressure after transplantation and degree of rejection. Heart period variability of the denervated donor atria did not change from early to late periods after transplantation, suggesting that vagal reinnervation of the donor heart had not occurred. These data indicate that baseline parasympathetic activity does not increase significantly during the first month after transplantation but increases significantly between months 3 and 6. PMID- 2239732 TI - Is the term "tricuspid atresia" appropriate? PMID- 2239731 TI - Natural history of cardiac rhabdomyoma in infancy and childhood. AB - Although spontaneous regression of cardiac rhabdomyoma has been reported, prognosis is still considered to be poor and surgery continues to be indicated. The experience with rhabdomyoma diagnosed in live infants over a 20-year period was reviewed. Diagnosis by angiography or echocardiography was accepted only if multiple tumors were present or if tuberous sclerosis was also diagnosed. Nine patients (3 diagnosed prenatally and the remaining 6 at age less than 8 months) were identified as having a total of 24 tumors. Measurements in 2 planes demonstrated at least some evidence of regression in 24 patients (100%), with 20 of 24 having complete resolution. One patient required delayed surgery for excision of a subaortic ridge that appeared at the site of a resolved tumor. Our findings suggest that pediatric cardiac rhabdomyoma is most often a benign condition in which spontaneous regression is the rule. Surgery is recommended only for patients with refractory dysrhythmias or severe hemodynamic compromise. PMID- 2239733 TI - Supported coronary angioplasty and standby supported coronary angioplasty for high-risk coronary artery disease. PMID- 2239734 TI - Prognosis of congestive heart failure in elderly patients with normal versus abnormal left ventricular systolic function associated with coronary artery disease. PMID- 2239736 TI - Safety and efficacy of in-office cardioversion for treatment of supraventricular arrhythmias. PMID- 2239735 TI - Natural history of posterobasal left ventricular aneurysm. PMID- 2239738 TI - Combined obstructive hypertrophic cardiomyopathy and stenotic congenitally bicuspid aortic valve. PMID- 2239737 TI - Effect of mitral regurgitation on the left ventricular outflow pressure gradient in obstructive hypertrophic cardiomyopathy. PMID- 2239739 TI - Experience with the Gianturco-Roehm Bird's Nest vena cava filter. PMID- 2239740 TI - Frequencies of reactions to iohexol versus ioxaglate. PMID- 2239741 TI - Safety and usefulness of transesophageal echocardiography in persons aged greater than or equal to 70 years. PMID- 2239742 TI - Nucleolar structure and synthetic activity during meiotic prophase and spermiogenesis in the rat. AB - The ultrastructure of nucleoli was examined in developing rat spermatocytes and spermatids, with the help of serial sections. In addition, the radioautographic reaction of nucleoli as examined in rats sacrificed 1 hr after intratesticular injection of 3H(5')-uridine and taken as an index of the rate of synthesis of ribosomal RNA (rRNA). Primary spermatocytes from preleptotene to zygotene have small nucleoli typically composed of fibrillar centers, a fibrillar component, and a granular component, within which are narrow interstitial spaces. During early and mid-pachytene, nucleoli enlarge to about nine times their initial size, with the fibrillar and granular components forming an extensive network of cords- a nucleolonema--within which are wide interstitial spaces. Meanwhile, there appear structures identical to the granular component but distinct from nucleoli; they are referred to as extranucleolar granular elements. Finally, from late pachytene to the first maturation division, nucleoli undergo condensation, as shown by contraction of fibrillar centers into small clumps, while fibrillar and granular components condense and segregate from each other, with a gradual decrease in interstitial spaces. In secondary spermatocytes, nucleoli are compact and rather small, while in young spermatids they are also compact and even smaller. Nucleoli disappear in elongating spermatids. In 3H-uridine radioautographs, nucleolar label is weak in young primary spermatocytes, increases progressively during early pachytene, is strong by the end of mid pachytene, but gradually decreases during late pachytene up to the first maturation division. In secondary spermatocytes and spermatids, there is no significant nucleolar label. In conclusion, rRNA synthesis by nucleoli is low in young spermatocytes. During pachytene, while nucleoli enlarge and form a lacy nucleolonema, rRNA synthesis increases gradually to a high level by the end of mid pachytene. However, during the condensation and segregation of nucleolar components occurring from late pachytene onward, the synthesis gradually decreases and disappears. The small, compact spermatids arising from the second maturation division do not synthesize rRNA. PMID- 2239743 TI - A morphologic study of bronchus-associated lymphoid tissue in turkeys. AB - Bronchus-associated lymphoid tissue (BALT) in normal turkeys of ages 1 day and 1, 2, 3, 4, 8, and 18 weeks was examined by light microscopy and by scanning and transmission electron microscopy. Turkey BALT resembled other mucosa-associated lymphoid tissues; it was made up of a population of lymphocytes covered by a specialized epithelium different from typical pseudostratified ciliated columnar bronchial epithelium. There were distinct age-related differences in BALT structure. Bronchus-associated lymphoid nodules were larger and more numerous in older turkeys. In 1-day- to 2-week-old turkeys, the primary cell type of BALT epithelium was nonciliated cuboidal; in 2-week old turkeys it was squamous; and in turkeys older than 4-weeks of age, the epithelium was primarily ciliated columnar. In 1- to 4-week old turkeys, large numbers of intraepithelial lymphocytes disrupted the normal organization of the epithelium. In older turkeys, epithelial and lymphoid cells were in discrete compartments separated by connective tissue. Lymphocytes in 1-day-old turkeys were found in loose aggregates around venules and within the epithelium. In 1-week old turkeys, lymphocytes were organized into compartments of morphologically similar cells. By 3-weeks of age, lymphocytes were present in distinct germinal centers. Epithelial cells of BALT did not have large numbers of apical vesicles and thus were not structurally specialized for antigen uptake by endocytosis. However, the epithelial barrier appeared to be disrupted over lymphoid nodules, suggesting that antigen would be readily available to lymphocytes and phagocytes in BALT. Age-related differences in turkey BALT structure may have functional consequences with respect to the respiratory immune response. PMID- 2239744 TI - Histologic changes in tissue components of the hyperplastic thyroid gland during its involution in the rat. AB - Male Fischer rats were fed a low-iodine diet containing thiouracil for 21 days to produce hyperplastic thyroid glands, and then fed a high-iodine diet for various time intervals, from 5 hr to 180 days, in order to study the morphological changes that occur during involution. Thyroids were fixed by perfusion fixation and embedded in Epon. Sections were examined by light microscopy. Initially at 0 days of involution (at the time of the change to the high-iodine diet), follicular lumens were very narrow and capillary lumens were very wide. The capsule was thick and infiltrated with mononuclear leukocytes. No obvious changes occurred for 1 day after the change in diet, but shortly thereafter capillary lumens began to narrow. By 4 days, most capillary lumens were close to normal size; capillaries formed a more or less normal bed except that many were embedded in a relatively thick or wide interfollicular matrix. This matrix was largely gone by 21 days. Between 1 and 21 days, follicular lumens dilated progressively as colloid accumulated. The density of staining of the accumulated colloid varied from follicle to follicle, and this variation was also observed in older controls. Inflammatory cells gradually disappeared from the capsule and most were gone by 15 days. Starting at approximately 15 days and continuing to 180 days, one or more disintegrating cells were found in some lumen profiles. Colloid goiters were not observed in these rats even after several months of involution. Some lumens were rather large, however, and small fractions of the follicles, both small and large, were bounded by flat cells and resembled "cold" follicles morphologically. PMID- 2239745 TI - Ultrastructural changes in thyroid epithelium during involution of the hyperplastic thyroid gland. AB - The ultrastructure of the thyroid epithelial cell was examined at various time intervals after induction of involution of the hyperplastic thyroid gland. Thyroids were made hyperplastic by the feeding of thiouracil in a Remington low iodine diet to male Fischer rats for 3 weeks. Involution was induced by replacing the thiouracil-containing diet with Purina Laboratory Chow, a high-iodine diet. During involution, organelles that play a role in the synthesis and secretion of thyroglobulin, such as the rough endoplasmic reticulum, Golgi apparatus, and apical vesicles, were well preserved and prominent features of the epithelial cell. The apical plasma membrane of many cells was highly irregular for approximately 2 weeks with signs suggesting rapid discharge of apical-vesical contents into the lumen of the follicle. Pseudopods and colloid droplets were present but were not very prominent features of the cell. No signs of extensive autophagy or obvious increased incidence of lysosomes were present, although there was an elevation in the incidence of small dense bodies starting about day 8, and prominent by 15 days. Some of these may be phagosomes formed from luminal debris. The observations indicate that involution of the hyperplastic thyroid in which there is maintenance of the protein synthetic apparatus and little sign of autophagy or death of the epithelial cells is remarkably different from phenomena occurring during involution of prostate or mammary glands. PMID- 2239746 TI - Comparison of a special class of epithelial cells in hyperplastic thyroids undergoing involution and in thyroids in hypophysectomized rats. AB - In male Fischer rats, a class of follicles with flat epithelium is present as a minor component of thyroid glands in which most of the follicles have cuboidal epithelium. These follicles occur in thyroids that have been made hyperplastic by feeding the rats thiouracil for 21 days and then allowing involution for 21 days or more. They also occur in older control rats. The follicles resemble in morphology, at the light-microscope level, the so-called "cold" follicles that occur in aged mice. We have examined the ultrastructure of the flat cells in these follicles and compared it with that of the flat cells occurring in the thyroid follicles of hypophysectomized rats. The cells in involution have abundant rough endoplasmic reticulum (RER) and few lysosomes and, in these respects, differ markedly from cells in hypophysectomized rats. The follicles with flat cells are surrounded by a normal incidence of blood capillaries, so that the cells do not appear to be deprived of access to an adequate supply of materials necessary to satisfy their metabolic requirements. Their abundant RER suggests that they have thyroid-stimulating hormone (TSH) receptors, so that the flat cell may be the result of some process occurring at a step distal to receptor coupling with TSH. Their occurrence in young rats after the induction of hyperplasia may be a consequence of cell multiplication producing a clone of neighboring abnormal cells that have an abnormally small cell height. PMID- 2239747 TI - Scleral calcification and photoreceptor cell death during aging and exposure to chronic stress. AB - Male and female Fischer 344 rats of three different ages (12, 18, and 25 months) have been examined for the presence of photoreceptor (PR) cell loss and for occurrence of scleral cartilage and bone formation. In addition, male and female rats, aged 11 months at the beginning of the experiments, were exposed to chronic stress for either 0.5, 2, 4, or 6 months. Photoreceptor cell death gradually increases during the aging process and is exacerbated by exposure to chronic stress. It is more severe in the peripheral than the central retina and exposure to stress increases this pattern of cell loss. The superior retina is more severely affected than the inferior hemisphere in aging and during stress. The incidence of scleral cartilage or bone formation increases with age in male and female rats, but with stress exposure an increase is seen in males only. Bone formations occur more frequently in male than in female animals and are almost always (97%) located in the superior hemisphere of the eye. Although there appears to be a direct relationship between photoreceptor cell death and the occurrence of scleral ossifications in group data, in individual eyes the bone formations are not always associated with severity of PR cell loss. The relationship of PR cell death and incidence of scleral ossification to gender and to exposure to stress supports a hypothesis for an endocrine basis of ocular aging. PMID- 2239748 TI - Morphometric analysis of vertebrae and intervertebral discs as a basis of disc replacement. AB - In this study measurements were obtained from 359 vertebrae and 215 intervertebral discs in an attempt to classify discs by their size. At the cervical and thoracic levels, this attempt was unproductive because of extensive variations. In the lumbar spine, discs were allocated to six size-matched groups and to two height-matched groups. The breadth of marginal rims were also measured with a view to provide surgeons operating on the spine with precise data on disc morphology to facilitate disc replacement. PMID- 2239749 TI - The effects of colchicine on the ultrastructure of odontogenic cells in the common skate, Raja erinacae. AB - Ultrastructural alterations induced by colchicine were investigated to determine the secretory activities of odontogenic cells during formation of tooth enameloid matrix in skates. Treated skate inner dental epithelial (IDE) cells did not display dilated cisternae of the granular endoplasmic reticulum (GER) nor accumulate Golgi-associated secretory granules at any dose level or time interval examined. This response was markedly different from that observed in teleost IDE cells synthesizing the enameloid collagen matrix. Treated skate IDE cells did show increased accumulations of glycogen-containing vesicles and intercellular glycogen associated with amorphous material, compared to controls. Additionally, the aberrant occurrence of large intracellular glycogen pools and amorphous material suggested that carbohydrate processing was a major function of skate IDE cells. Treated odontoblasts associated with enameloid matrix formation sometimes showed dilated GER cisternae, but procollagen secretory granules were not observed. Instead, electron dense material was present within the Golgi cisternae, tubular granules, and large granules. Some electron-dense material appeared to be shunted to a resorptive pathway via multivesicular bodies in treated odontoblasts. The continuity of tubular granules with the enameloid matrix suggested that they contained precursors of the enameloid matrix, and possibly the periodic, 17.5-nm cross-striated, "giant" fibers. Treated odontoblasts associated with predentin collagen matrix deposition showed dilated GER cisternae and accumulations of procollagen secretory granules, features consistent with the function of active collagen synthesis and secretion. The findings indicate that (1) skate IDE cells do not synthesize enameloid collagen as found in bony fish tooth development; (2) skate IDE cells do process glycogen for secretion into the enameloid matrix; (3) collagen, although present, is not a major constituent of skate enameloid matrix; (4) enameloid "giant" fibers are unique to elasmobranchs; and (5) odontoblasts synthesize and secrete proteins other than collagen into the enameloid matrix. PMID- 2239750 TI - Energy content of diets of variable amino acid composition. AB - Variation in the distribution of dietary nitrogen among the different amino acids is one factor that can modify the calorie equivalent per weight of amino acid or protein. This is important to consider when experimental diets with different amino acid compositions are compared and when indirect calorimetry is used to determine substrate oxidation rates. We developed a computer program to compute the energy content, oxygen equivalent, and respiratory quotient for arbitrary mixtures of amino acids and representative carbohydrates and fats. The calorie content of individual free amino acids was calculated by correction of the heat of combustion for the incomplete oxidation of amino acids characteristic of humans. Although these computations were presented before, we not report the limit of applicability of published values and the availability of the computer program to do these calculations. PMID- 2239751 TI - Prediction of 24-h energy expenditure and its components from physical characteristics and body composition in normal-weight humans. AB - The applicability of body composition as estimated by the bioimpedance method to predict energy expenditure (EE) was studied. Ten healthy subjects underwent measurement of body composition and 24-h energy expenditure (24-h EE) twice in a respiration chamber on a fixed program. The 24-h EE and its components, sleeping EE (SEE), basal EE (BEE), and daytime EE, for an individual were very reproducible (coefficient of variation 2.3%, 1.4%, 5.0%, & 3.1%, respectively). The variability of 24-h EE among subjects was 11.4% but only 4.1% when adjusted for differences in lean body mass (LBM). LBM was the best determinant of 24-h EE, BEE, and SEE and accounted for 91-93% of the interindividual variance of EE. The prediction equations were 24EE (kcal/d) = 390 + 33.3 LBM (r2 = 0.93, P = 0.000001), SEE (kcal/h) = 9.8 + 1.1 LBM (r2 = 0.92, P = 0.000001), and BEE (kcal/h) = -3.1 + 1.35 LBM (r2 = 0.91, P = 0.000002). In conclusion, 24EE, BEE, and SEE can be predicted with a high degree of precision from LBM as estimated by bioimpedance in normal-weight subjects. PMID- 2239752 TI - Growth, thermogenesis, and hyperphagia. AB - Resting metabolic rate is demonstrated to be a function of fat-free mass and a growth variable related to food-energy-input imbalance rate. By use of obligatory energy expenditure terms, the two-reservoir energy model applied to hyperphagia shows that growth of the fat-free mass is rapid whereas that of the fat store is slow and that the growth of both is bounded. Most of the excess energy at the onset of hyperphagia initially goes into the fat store, but this decreases with time until the greater fraction is diverted to the fat-free mass. The two reservoir model predicts that weight gain per unit of excess energy is not constant but decreases monotonically until ultimately reaching an asymptotic value. Departure of theory and experiment in the long term suggests that facultative considerations become increasingly important. PMID- 2239753 TI - Rate and amount of weight gain during adolescent pregnancy: associations with maternal weight-for-height and birth weight. AB - This study presents information on the course and rates of weight gain and the associations among weight gain, prepregnancy weight-for-height, and infant birth weight, based on a total sample of 1419 uncomplicated term deliveries to adolescents. The distribution of cumulative weight gain indicates that for adolescents not only is the median gain at term (14.2-15.5 kg) significantly in excess of that reported for adults, but also weight-gain velocity is greater from the beginning of pregnancy. Although the contributions of prepregnancy weight-for height and weight gain to birth weight may be independent, they are not necessarily additive. Birth weight does not appear improved for the infants of overweight adolescents except when weight gain is low (less than 11.1-12.3 kg at term), and, for Puerto Rican and black adolescents, birth weight is not further improved at any maternal prepregnancy body mass index (weight-for-height) with excessive weight gains (greater than 17.9-19.3 kg at term). PMID- 2239754 TI - Maintenance and relapse after weight loss in women: behavioral aspects. AB - Obese women who regained weight after successful weight reduction (relapsers, n = 44); formerly obese, average-weight women who maintained weight loss (maintainers, n = 30); and women who had always remained at the same average, nonobese weight (control subjects, n = 34) were interviewed. Most maintainers (90%) and control subjects (82%) exercised regularly, were conscious of their behaviors, used available social support (70% and 80%, respectively), confronted problems directly (95% and 60%, respectively), and used personally developed strategies to help themselves. Few relapsers exercised (34%), most ate unconsciously in response to emotions (70%), few used available social support (38%), and few confronted problems directly (10%). These findings suggest the advisability of development and prospective evaluation of individualized treatment programs designed to enhance exercise, coping skills, and social support. PMID- 2239755 TI - Diet and female sex hormone concentrations: an intervention study for the type of fat consumed. AB - A possible mechanism by which dietary fat may influence the development of breast cancer is by influencing the concentration of female sex hormones. This study investigated the effect of alteration in the type of fat consumed on concentrations of female sex hormones in serum. Female volunteers were randomly assigned to continue on their usual meat-eating diet, change to a vegetarian diet, or change to a diet that was predominantly vegetarian but where fish was consumed at least three times per week. Change to the vegetarian or fish diet had little effect on diet total hormone concentrations; however, the amount of estradiol was significantly decreased in the vegetarian group. When nutrient consumption was correlated with hormone concentrations, prolactin was directly associate with fat consumption, sex-hormone-binding globulin was inversely associated with fat consumption (particularly cholesterol consumption), and the proportion of nonprotein-bound estradiol was directly associated with complex carbohydrate consumption. PMID- 2239756 TI - Impaired thermoregulation and thyroid function in iron-deficiency anemia. AB - Ten women with iron-deficiency anemia, 8 with depleted iron stores (nonanemic), and 12 control women, all of similar body fatness, were exposed to a 28 degrees C water bath to test the hypothesis that iron-deficiency anemia impairs thermoregulatory performance. The anemic women had lower rectal temperatures than did control women (36.0 +/- 0.2 vs 36.2 +/- 0.1 degree C, respectively, P = 0.001) and a lower rate of oxygen consumption (5.28 +/- 0.26 vs 5.99 +/- 0.29 mL.min-1.kg body wt-1, respectively, P = 0.04) at 100 min of cold exposure. Plasma thyroxine and triiodothyronine concentrations were significantly (P less than 0.002) lower in anemic than in control women at baseline and during cold exposure. Responses of iron-depleted subjects were similar to those of control subjects. Iron supplementation corrected the anemia, significantly (P = 0.03) improved rectal temperature at 100 min, and partially normalized plasma thyroid hormone concentrations. Plasma catecholamines were unaffected by iron status. This experiment demonstrates a functional consequence of iron-deficiency anemia in the balance of heat production and loss and suggests that thyroid-hormone metabolism may be responsible. PMID- 2239757 TI - Role of carnitine in utilization of dietary medium-chain triglycerides by term infants. AB - The role of carnitine in oxidation of dietary medium-chain fatty acids (as medium chain triglycerides) was studied in term human infants. Infants were fed, alternately, formulas with fat content that was predominantly long-chain triglycerides, or 40% medium-chain triglycerides. Urinary acylcarnitine excretion was significantly higher and the ratio of free to total carnitine was significantly lower when infants were fed the formula with medium-chain triglycerides. Two groups of 10 infants were fed a commercial soy-protein-based formula modified to contain 40% of fat calories as medium-chain triglycerides and with or without added L-carnitine. By 56 d, infants fed the formula without added L-carnitine excreted significantly more medium-chain dicarboxylic acids than did the same infants at 28 d and significantly more than infants consuming the carnitine-supplemented formula at either 28 or 56 d. Results are consistent with a role for carnitine in metabolism of dietary medium-chain triglycerides in infants. PMID- 2239759 TI - Medium-chain fatty acids: evidence for incorporation into chylomicron triglycerides in humans. AB - The purpose of this study was to evaluate the fatty acid composition of chylomicron triglycerides isolated from subjects fed liquid-formula diets containing 40% of total energy as medium- (C8:0 and C10:0) or long-chain (C16 C18) triglycerides (MCT, LCT) for 6 d. Medium-chain fatty acids (MCFA) comprised 8% of total chylomicron triglyceride fatty acids after the first MCT meal. After 6 d of continued MCT feeding, chylomicron triglyceride MCFA content increased to 13%. When subjects were fed the LCT (soybean oil) diet, C16:0, C18:1, and C18:2 comprised nearly 90% of the chylomicron triglyceride fatty acids. The mass of triglyceride transported in chylomicrons isolated from subjects fed the MCT diet was approximately 20% of that found when subjects consumed the LCT diet. We conclude that although total triglyceride production during MCT ingestion is low, the chylomicron triglycerides that are synthesized contain significant amounts of MCFA. PMID- 2239758 TI - A mixed Australian fish diet and fish-oil supplementation: impact on the plasma lipid profile of healthy men. AB - Twelve healthy men were fed in turn three diets for 6 wk each in a 3 x 3 randomized block design: a control diet (essentially fish free), a fish diet (200 g lean Australian fish flesh/d), and the same fish-based meal but supplemented with 5 g fish oil/d. Dietary eicosapentaenoic acid [EPA, 20: 5n-3 (omega-3)] was strongly associated with erythrocyte membrane EPA (r = 0.908 at 6 wk), strengthening its value as a measure of compliance in fish and fish-oil feeding trials. On the fish diet, subjects had increased incorporation of n-3 polyunsaturated fatty acids (PUFAs) at the expense of n-6 PUFAs in their erythrocyte membranes. When the fish-based diet was supplemented with fish oil (5 g/d), there was a significant lowering of plasma triacylglycerol (-0.16 +/- 0.24 mmol/L; mean +/- SD). No change in plasma total cholesterol was detected although the fish + oil diet produced a reduction in very-low-density-lipoprotein cholesterol (-0.24 +/- 0.26 mmol/L). PMID- 2239760 TI - Flavin composition of human milk. AB - The identity and quantity of greater than 95% of the flavins present in human milk were assessed by acid-phenol extractions followed by high-performance liquid chromatography. Flavin adenine dinucleotide (FAD) and riboflavin were the predominant flavins, followed by 10-(2'-hydroxyethyl)-flavin. In addition, traces of 7 alpha- and 8 alpha-hydroxyriboflavins (7-hydroxymethylriboflavin and 8 hydroxymethylriboflavin, respectively) were detected. The flavin content of human milk samples in this study was higher than contents reported in earlier studies where no correction for the internal fluorescence quenching of FAD was made. This finding may have implications for dietary recommendations concerning both lactating women and infants. In practical terms, the types and amounts of flavins in human milk are very similar to those recently reported for cow milk. PMID- 2239762 TI - Obesity and iron status in menstruating women. AB - The relationship between iron stores and obesity in menstruating women was studied in 20 obese and 20 nonobese women matched for age and contraception. Although no difference was observed in serum iron or total-iron-binding capacity, the obese group showed significantly higher hemoglobin (137 +/- 9 vs 10 g/L, mean +/- SD; P less than 0.01), hematocrit (0.41 +/- 0.02 vs 0.39 +/- 0.03, P less than 0.05), and serum ferritin concentrations (48.0 +/- 44.3 vs 25.8 +/- 19.5 micrograms/L, P less than 0.05). There was no difference between obese and nonobese women in either the menstrual-cycle interval or the duration of the menstrual flow. Iron intake was significantly higher in the obese group (15.9 +/- 2.9 vs 14.1 +/- 2.9 mg/d, P less than 0.05). These results suggest that obese menstruating women are at low risk of depleting iron stores, possibly because of high iron intake. Iron-fortification programs might thus be undesirable in such subjects. PMID- 2239763 TI - Effects of resection on absorption and secretion of divalent cations by small intestine of rat. AB - Resection increases villus height and crypt depth of remaining intestine. We examined functional consequences of resection by measuring absorption of strontium and secretion of calcium and magnesium by proximal and distal segments remaining after resecting 70% of mid small intestine. Compared with the transected control group, resection decreased strontium absorption per unit weight of mucosa (specific absorption) in the proximal segment. The decreased specific absorption was compensated by increased mucosal growth in the resected group so that absorption per unit length of segment (per cm) was the same in both groups. Resection increased secretion of calcium and magnesium by 66% per unit weight of mucosa and by 145%/cm in the distal segment. Comparing proximal with distal segments in the resected group, secretion was greater in distal for calcium and in proximal for magnesium. Intestinal resection causes responses in absorption and secretion of divalent cations important in mineral homeostasis. PMID- 2239761 TI - Selenium intake, age, gender, and smoking in relation to indices of selenium status of adults residing in a seleniferous area. AB - Duplicate meals, serum, whole blood, and toenails were collected every 3 mo for 1 y from a group of 44 free-living adults residing in high-selenium areas of South Dakota and Wyoming to assess the relation of selenium intake to indices of selenium status. The average selenium values for the group were as follows: dietary intake, 174 +/- 91 micrograms/d (mean +/- SD), 2.33 +/- 1.08 micrograms/kg body wt; serum, 2.10 +/- 0.38 mumol/L; whole blood, 3.22 +/- 0.79 mumol/L; and toenails, 15.2 +/- 3.0 nmol/g. Selenium intake (micrograms/kg body wt) was strongly correlated (all values, P less than 0.01) with selenium concentration of serum (r = 0.63), whole blood (r = 0.62), and toenails (r = 0.59). Men and women had similar mean values of serum, whole blood, and toenail selenium despite higher selenium intakes in men. Smokers had lower tissue selenium concentrations than did nonsmokers due, at least in part, to lower selenium intake. Age was not associated with tissue selenium content. Of the variables examined selenium intake was clearly the strongest predictor of tissue selenium concentration. PMID- 2239764 TI - Mother-daughter pairs: spinal and femoral bone densities and dietary intakes. AB - Bone mineral density (BMD) of the lumbar spine (L1-L4) and femur (femoral neck, Ward's triangle, and trochanter) was measured in 37 healthy, white mother daughter pairs by dual-photon absorptiometry. Mothers and daughters were aged 52 +/- 7 and 25 +/- 4 y (mean +/- SD), respectively. Three-day dietary intakes were evaluated. Significant correlations between mother-daughter pairs for BMD of all lumbar and femoral areas [except for L2 (r = 0.26, P = 0.054)] indicated familial resemblances in bone mineralization. Total calcium intake was significantly correlated with three BMD values for the daughters (L2, femoral neck, and trochanter) but not for the mothers. When mothers were classified as pre- (n = 20) or postmenopausal (n = 17), correlation coefficients for BMD were higher for premenopausal mothers and their daughters and lower for postmenopausal mothers and their daughters, except for the trochanter. The results suggest that the nature of inheritance of bone mass of women may have at least two components, one influencing the level of peak bone mass and one related to bone loss at menopause. PMID- 2239765 TI - Factors that influence peak bone mass formation: a study of calcium balance and the inheritance of bone mass in adolescent females. AB - We suggested that calcium may be an important determinant of peak bone mass. For further elucidation, calcium balances in adolescent females with different calcium intakes (270-1637 mg/d), and a 2-y intervention study of calcium supplementation were performed. Hereditary influences on bone status were also evaluated by comparing subjects' and parents' bone mass. The main determinant of calcium balance was calcium intake; net calcium absorption increased with intake and urinary calcium did not change. Adolescent females retained 200-500 mg Ca/d, suggesting that inadequate calcium intake may translate into inadequate calcium retention and a reduction in peak bone mass. There was a more pronounced increase in bone mass over time in the calcium-supplemented group (1640 mg Ca/d) than in the control group (750 mg Ca/d), but the differences between bone mass measurements were not statistically significant, possibly because of a type II error. By the age of 16 y daughters had accumulated 90-97% of the bone mass of their premenopausal mothers. PMID- 2239766 TI - Dietary fat and risk of breast cancer. AB - The relationship between dietary fat and subsequent risk of breast cancer was studied in 3988 initially cancer-free Finnish women aged 20-69 y. During a follow up period of 20 y, 54 breast-cancer cases were diagnosed. Risk of breast cancer was significantly inversely related to energy intake and nonsignificantly inversely related to absolute fat intake. A positive association between energy adjusted total fat intake and occurrence of breast cancer was also observed. The relative risk in the highest tertile as compared with the lowest tertile was 1.7 (95% confidence limits 0.6-4.8). The corresponding relative risks were 1.4 (0.5 3.7) for saturated fatty acids, 2.7 (1.0-7.4) for monounsaturated fatty acids, 1.2 (0.6-2.8) for polyunsaturated fatty acids, and 2.2 (1.0-5.0) for cholesterol intake. Adjustment for different potential confounding factors did not alter the results. The present data suggest that breast cancer is associated inversely with energy intake and weakly positively with energy-adjusted fat intake. PMID- 2239767 TI - Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A. AB - A case-control study of breast cancer was conducted in Buffalo. Participants completed a food frequency questionnaire and donated a fasting blood sample before definitive workup for breast masses. Dietary and plasma concentrations of carotenoids and retinol for 83 women found to have breast cancer were compared with those of 113 women found to be free of breast cancer (control subjects). There were no case-control differences in dietary estimates of vitamin A intake or in plasma alpha-carotene and lycopene. However, subjects with breast cancer had lower concentrations of plasma beta-carotene than did control subjects (P = 0.02). There was no overall association between plasma retinol and breast cancer but a positive relationship was observed between retinol and breast cancer in the subgroup with low beta-carotene values. These results suggest that low plasma beta-carotene is associated with increased risk of breast cancer. Other studies will need to determine whether low carotene concentrations are a subtle effect of the disease or might be causally related to breast cancer. PMID- 2239768 TI - Dietary predictors of symptom-associated gallstones in middle-aged women. AB - In 1980, 88,837 women aged 34-59 y completed a semiquantitative food frequency questionnaire and were followed for 4 y. Four hundred thirty-three women reported a cholecystectomy for recent cholecystitis, and 179 reported unremoved, newly symptomatic gallstones diagnosed by ultrasound or x ray. Among the 59,306 women with Quetelet's index of relative weight less than 25 kg/m2, inverse associations were observed between intakes of vegetable fat and vegetable protein and the risk of reportedly symptomatic gallastones, after adjusting for age, Quetelet's index in 1980, weight change between 1976 and 1980, energy intake, and alcohol intake. The relative risk in the highest quintile of vegetable fat intake, as compared with the lowest quintile, was 0.6 [95% confidence interval (CI), 0.4-0.9], and the corresponding relative risk for vegetable protein intake was 0.7 (95% CI, 0.6 0.9). No significant associations were found with energy-adjusted intakes of cholesterol, animal fat, animal protein, carbohydrate, or sucrose. PMID- 2239769 TI - Urinary organic acid excretion during feeding of medium-chain or long-chain triglyceride diets in patients with non-insulin-dependent diabetes mellitus. AB - Medium-chain triglycerides (MCTs) are absorbed and metabolized differently from long-chain triglycerides (LCTs). Recent data indicate that MCTs may be useful as a dietary substitute in a variety of clinical disorders. The current studies were undertaken to characterize urinary organic acid excretion in patients with non insulin-dependent diabetes mellitus during 4 d of an LCT or MCT diet. Urinary excretion of the dicarboxylic acids adipic, suberic, and 3-hydroxysebacic and the (omega-1) hydroxylation products 5-hydroxyhexanoic acid and 7-hydroxyoctanoic acid, was increased during MCT feeding as compared with LCT feeding. Urinary suberic and 7-hydroxyoctanoic acid excretions were increased 55- and 30-fold, respectively, during the MCT-substituted diet. Urinary organic acid profiles provide information on the fate of lipids during MCT feeding and may also be useful in assessing complicance during clinical trials employing MCT-substituted diets. PMID- 2239770 TI - Nutrition factors in relation to cellular and regulatory immune variables in a free-living elderly population. AB - Aging is associated with a greater susceptibility to nutrition deficiencies and to progressive senescence of the immune system. To test whether nutrition status contributes to the immunologic changes observed in elderly individuals, we examined the relationship between nutrition status and in vitro indices of immune responses in 82 healthy, free-living elderly individuals. Nutrition status was assessed by anthropometric measurements, 7 d food records, and blood concentrations of selected nutrients. Using regression analyses, we found that none of the nutrition factors was associated with cytotoxic activity of natural killer (NK) cells against the leukemic cell line K562. However, our results suggest that the dietary intakes of vitamins E and D negatively influenced the activity of interleukin 2 (IL-2) measured by a bioassay in which the CTLL cell line was used. An association may exist between particular aspects of nutrition status and regulation of immune response by IL-2. The need for further studies is emphasized. PMID- 2239771 TI - Dietary habits of smokers, people who never smoked, and exsmokers. AB - A large database on hospital patients with illnesses not related to tobacco or alcohol was used to investigate the dietary habits of males and females who never smoked, who were exsmokers, and who currently smoked. Smoking was positively related to meat consumption and negatively related to cereal consumption in males. Both male and female smokers consumed fewer vegetables and fruits but more alcohol and coffee than did people who never smoked. Exsmokers' diets were similar to those of people who never smoked. These results emphasize the importance of ruling out potential confounders or effect modifiers when studying the role of meat, milk, fruits, vegetables, cereal, coffee, or alcohol intake in the etiology of tobacco-related diseases. PMID- 2239772 TI - Maternal weight gain in low-income black and Hispanic women: evaluation by use of weight-for-height near term. AB - This study determined the prevalence of low maternal weight gain among a target group of low-income black and Hispanic women and compared weight-for-height near term with total weight gain during pregnancy as an index of birth-weight classification. One-third (30.8%) of 325 women had weights near term less than 120% of their standard pregravid weight-for-height; there was little variation by ethnic group. After adjusting for gestational age as a covariate of birth weight (P = 0.0001), maternal weight-for-height near term (P = 0.0010), ethnicity (P " 0.0068), and parity (P = 0.0083) significantly influenced birth weight. Women with near-term weights greater than or equal to 120% of their standard pregravid weight-for-height delivered infants with higher birth weights (P = 0.001). Comparison of weight-for-height near term with total weight gain as an index of birth-weight classification (less than or greater than or equal to 3000 g) revealed that the two methods differ in terms of sensitivity and specificity with variation in pregravid weight. PMID- 2239773 TI - Food fights: deciding about diet and disease. PMID- 2239774 TI - Basic and clinical aspects of regional fat distribution. PMID- 2239775 TI - Effects of common illnesses on infants' energy intakes from breast milk and other foods during longitudinal community-based studies in Huascar (Lima), Peru. AB - To assess the effects of common infections on dietary intake, 131 Peruvian infants were observed longitudinally. Home surveillance for illness symptoms was completed thrice weekly, and food and breast-milk consumption was measured during 1615 full-day observations. Mean (+/- SD) energy intakes on symptom-free days were 557 +/- 128 kcal/d (92.4 +/- 26.5 kcal.kg-1.d-1) for infants aged less than 181 d and 638 +/- 193 kcal/d (77.7 +/- 25.7 kcal.kg-1.d-1) for infants aged greater than 180 d. Statistical models controlling for infant age, season of the year, and individual showed significant 5-6% decreases in total energy intake during diarrhea or fever. There were no changes with illness in the frequency of breast-feeding, total suckling time, or amount of breast-milk energy consumed. By contrast, energy intake from non-breast-milk sources decreased by 20-30% during diarrhea and fever, and the small decrements in total energy consumption during illness were explained entirely by reduced consumption of non-breast-milk foods. PMID- 2239776 TI - Cholesterol-lowering effect of skim milk from immunized cows in hypercholesterolemic patients. AB - The effect of skim milk from cows immunized against a variety of human intestinal bacteria on serum cholesterol concentrations was examined in 11 patients with primary hypercholesterolemia in a 24-wk, randomized, double-blind, placebo controlled, crossover study. After a 4-wk baseline period, patients were treated for 8 wk either with skim milk from immunized cows (active) or with control skim milk (placebo) followed by an 8-wk period with the treatment order reversed. Eight weeks of active treatment with skim milk from immunized cows reduced serum total cholesterol concentrations by 0.52 +/- 0.59 mmol/L (mean +/- SD; P less than 0.025), or 8%, LDL cholesterol by 0.16 +/- 0.59 mmol/L (NS), or 4%, and the atherogenic index (total cholesterol/HDL cholesterol) by 0.42 +/- 1.85 (P less than 0.05), or 8%, compared with the placebo treatment. Reversal of the favorable development occurred upon cessation of active treatment. We conclude that daily supplementation of a normal diet with skim milk from immunized cows can result in a significant reduction of elevated blood cholesterol concentrations. PMID- 2239777 TI - Erythrocyte fatty acids, plasma lipids, and cardiovascular disease in rural China. AB - Cardiovascular disease (CVD) mortality (coronary heart disease, hypertensive heart disease, and stroke), plasma lipids, and red blood cell fatty acid composition were examined in an ecologic study in 65 rural counties in the People's Republic of China. Means of plasma total cholesterol, triglyceride, low density-lipoprotein (LDL) cholesterol, and high-density-lipoprotein (HDL) cholesterol concentrations were substantially lower and the ratio of HDL cholesterol to total cholesterol was higher in this Chinese population than in Western populations. Mortality rates for CVD in China were well below Western values. Within China neither plasma total cholesterol nor LDL cholesterol was associated with CVD. A strong inverse correlation between red blood cell oleate concentrations and CVD was observed. However, red blood cell oleate concentrations were not associated with plasma cholesterol but were strongly negatively associated with arachidonate concentrations, suggesting potential diminution of CVD by oleate through reduced platelet aggregability. The results indicate that geographical differences in CVD mortality within China are caused primarily by factors other than dietary or plasma cholesterol. PMID- 2239778 TI - Protein-energy requirements of prepubertal school-age boys determined by using the nitrogen-balance response to a mixed-protein diet. AB - Short-term nitrogen-balance response to a vegetable-protein mixed diet and to a milk-egg protein diet was tested in eight healthy male children 8-10 y old. They received 96, 128, 160, and 192 mg N.kg body wt-1.d-1 for 10 d while on the mixed diet and 160 mg N.kg-1.d-1 on the milk-egg diet. The mean regression equation was nitrogen balance = 0.52 (nitrogen intake) -68.3, all in mg N.kg-1.d-1. Apparent nitrogen digestibility was 82% and 86% for the mixed and milk-egg diets, respectively, when the subjects received 160 mg N.kg-1.d-1. Mean nitrogen intake for satisfactory nitrogen retention on the mixed diet was 150 mg N.kg-1.d-1; the suggested protein recommended allowance to cover 97.5% of the population was derived by using a CV of 12.5% is 1.2 g protein.kg-1.d-1. We conclude that present recommendations are adequate for short-term nitrogen retention; long-term studies are needed to evaluate the chronic safety of this protein allowance. PMID- 2239779 TI - Continuous glucose for treatment of patients with type 1 glycogen-storage disease: comparison of the effects of dextrose and uncooked cornstarch on biochemical variables. AB - Responses to uncooked cornstarch (UCS), dextrose (Dex), and a 3:1 mixture (UCS:Dex) were determined in seven children with type 1 glycogen-storage disease (GSD-1). UCS maintained blood glucose (BG) and serum insulin concentrations between 3.5 +/- 0.3 and 4.0 +/- 0.4 mmol/L (mean +/- SEM) and 50 +/- 7 and 79 +/- 22 pmol/L, respectively, in six of the seven patients for 4 h. Only four of seven patients completed the 4-h test after UCS:Dex (BG 2.9 +/- 0.3 mmol/L): After Dex, tests had to be stopped in all patients by 150 min after initiation (BG 2.7 +/- 0.4 mmol/L). Two methods of providing dietary glucose overnight, continuous intragastric glucose infusion (COG) and intermittent UCS at 2100 and 0200, were compared by monitoring metabolites and glucoregulatory hormones. The use of UCS in amounts equal to the calculated glucose production rate is an effective method of providing a continuous dietary source of glucose overnight to patients with GSD-1. PMID- 2239780 TI - Physical growth and development of children with type 1 glycogen-storage disease: comparison of the effects of long-term use of dextrose and uncooked cornstarch. AB - Thirteen patients with type 1 glycogen-storage disease (GSD-1) were studied to compare the effects on biochemical control and growth of 2 y of therapy with intermittent feedings of uncooked cornstarch (UCS) at the fasting glucose production rate and therapy with continuous overnight glucose (COG) and dextrose feedings during the day. Mean biochemical abnormalities for the groups were minimized but not normalized by either COG or UCS. Growth progressed normally when COG was started by 1.2 y of age and normal growth rate was maintained by UCS. Weight increased from 101 +/- 3% ideal body weight at onset of COG to 127 +/ 5% during COG and the first year of UCS therapy but did not increase further in the second year. When growth failure occurred before onset of COG [-3.7 SD score for chronological age (SDSCA)], only partial correction (-1.9 SDSCA) to genetic potential for height occurred. Intermittent feeding of UCS provides an effective alternative to COG for the treatment of GSD-1. PMID- 2239781 TI - Dietary carbohydrate and intensity of interval swim training. AB - We tested the effects of 9 d of a high-carbohydrate diet (80% of calories as CHO, 80% CHO diet) vs. a moderate-CHO diet (43% of calories as CHO, 43% CHO diet) on the abilities of collegiate swimmers to maintain a high intensity of interval swim training. Interval swim times and other physiological indices were recorded the last 5 d of each diet. Swim-interval distances ranged from 50-m interval sets to continuous 3000-m swims. There were no diet effects on mean swim velocities for any interval distance, and mean (+/- SEM) velocities for all swims were identical for both diets. There were no diet effects on the physiological indices; however, postswim blood lactate concentrations were higher after the 80% CHO diet. When mean +/- SEM daily caloric intake is 19.56 +/- 2.16 MJ (4675 +/- 516 kcal) for swimmers undertaking swim training to develop aerobic capacity, an 80% CHO diet provides no advantage over a 43% CHO diet for maintaining interval swim-training intensity. PMID- 2239782 TI - The modified relative-dose-response assay as an indicator of vitamin A status in a population of well-nourished American children. AB - The relative-dose-response (RDR) assay first proposed by Underwood has proved to be a useful indicator of marginal vitamin A status. We suggested that 3,4 didehydroretinol might be used in a simpler assay that requires only one blood sample for analysis. In the present study 24 healthy children aged 3.7-7.1 y were given 100 micrograms 3,4-didehydroretinyl acetate/kg body wt in corn oil, followed by ice cream (90 mL). A blood sample was taken 2, 4, 5, 6, 8, 10, or 24 h after the dose. The mean ratio of dehydroretinol to retinaol (DR-R ratio) plateaued at approximately 0.02 in the plasma between 4 and 10 h. Only three children showed ratios greater than 0.03. Upon reinvestigation, the DR-R ratio remained greater than 0.03 in one child at 5 h. After vitamin A treatment the ratio decreased to 0.019. Thus, a tentative DR-R cutoff ratio for a satisfactory vitamin A status in healthy American children is 0.03. PMID- 2239783 TI - Vitamin A status in preschool-age Indonesian children as assessed by the modified relative-dose-response assay. AB - The modified relative-dose-response (MRDR) assay has been validated in rats as a function of vitamin A status and tested in a group of American children. In this study the MRDR assay was applied to West Javan children who are at risk of being vitamin A deficient. Of 86 children enrolled, 75 were tested. In a time-course study involving 22 children aged 3.7-5.3 y, blood samples were taken at different times after doses of 0.35 mumol 3,4-didehydroretinyl acetate/kg body wt. Generally, the ratio of dehydroretinol to retinol (DR-R ratio) peaked between 4 and 8 h. Thereafter, in a survey of 53 children aged 0.6-4.8 y, single blood samples were drawn 5 h after the dehydroretinyl acetate dose. The DR-R ratio ranged from 0.0028 to 0.169. With a DR-R ratio of 0.03 as the cutoff value, 62% of the children were judged to be of marginal vitamin A status. PMID- 2239784 TI - Vitamin B-12: low milk concentrations are related to low serum concentrations in vegetarian women and to methylmalonic aciduria in their infants. AB - In a group of 13 strict vegetarian and 6 omnivorous lactating women, relationships were studied among maternal milk and serum vitamin B-12, and milk vitamin B-12 and infant urinary methylmalonic acid (MMA) excretion. Milk vitamin B-12 concentrations were lower in women consuming a strict vegetarian diet compared with an omnivorous diet. Milk vitamin B-12 was inversely related to length of time on a vegetarian diet and positively correlated with maternal serum vitamin B-12 concentrations. Infant urinary MMA excretion was inversely related to milk vitamin B-12 concentrations less than 362 pmol/L. The 1989 recommended dietary allowance for vitamin B-12 of 221 pmol/d for infants is close to the intake below which infant urinary MMA excretion is increased. We conclude that the current RDA for infants provides little margin of safety. PMID- 2239785 TI - Influence of folate status and polyphenol intake on thiamin status of Irish women. AB - The relationship of folate status and polyphenol intake to thiamin status was studied in 80 randomly selected elderly and young Irish women, with key variables affecting thiamin nutrition controlled for. Folate, thiamin, and polyphenol intakes were measured during a 4-wk baseline (elderly and young) and 6-wk double blind (elderly) supplementation period. Only elderly subjects were randomly assigned to placebo, folic acid (400 micrograms), thiamin (10 mg), or folic-acid plus-thiamin groups. Thiamin status (TPP effect) was not affected by folate status (plasma and erythrocyte folate) during the baseline period or with folic acid supplementation alone. Polyphenol intake was not correlated with thiamin status. Only thiamin intake and thiamin supplementation significantly affected thiamin status. Because the majority of subjects (102 of 160) were initially thiamin deficient, enrichment of Irish grain products with thiamin is recommended. PMID- 2239786 TI - Chronic ethanol feeding and acute ethanol exposure in vitro: effect on intestinal transport of biotin. AB - This study examined the effects of chronic ethanol feeding and acute ethanol exposure in vitro on biotin transport in rat intestine. Transport studies were performed with intestinal everted sacs. Ethanol was fed to rats for 6-7 wk. Compared with pair-fed controls, ethanol feeding significantly decreased plasma biotin concentrations and transport at physiological concentrations (0.01, 0.1, and 0.3 mumol/L) but not at pharmacological concentration (100 mumol/L). When added to the incubation medium of everted jejunal sacs from dry-food-fed rats, ethanol (2% vol:vol) significantly inhibited the transport of biotin at a physiological concentration (0.1 mumol/L) but not at a pharmacological concentration (100 mumol/L). The inhibitory effect of ethanol on the transport of 0.1 mumol biotin/L increased with increasing concentration of ethanol in the incubation medium [0.5% to 5% (vol:vol)]. Acetaldehyde, the major ethanol metabolite, also significantly inhibited biotin transport at 0.2% (vol:vol). These data demonstrate that chronic ethanol feeding and acute ethanol exposure in vitro inhibit the intestinal transport of biotin by the carrier-mediated process. Chronic ethanol feeding is also associated with a significant decrease in plasma biotin concentrations. The ethanol-induced inhibition in intestinal transport of biotin may be a contributing factor in reducing plasma biotin concentrations. PMID- 2239787 TI - Iodine and selenium deficiency associated with cretinism in northern Zaire. AB - Selenium status was determined in an endemic-goiter area and in a control area of Zaire. Compared with the reference values of a noniodine-deficient area, serum selenium in subjects living in the core of the northern Zaire endemic-goiter belt (Karawa villages) was seven times lower in 52 school-children and similarly low in 23 cretins; erythrocyte glutathione peroxidase (RBC-GPX) was five times lower in schoolchildren and still two times lower in cretins (P = 0.004). In a less severely iodine-deficient city of the same endemia (Businga), selenium status was moderately altered. RBC-GPX activity was linearly associated with serum selenium concentration up to a value of 1140 nmol/L and leveled off at approximately 15 U/g Hb at greater selenium concentration. At Karawa villages, selenium supplementation normalized both the serum selenium and the RBC-GPX. This combined iodine and selenium deficiency could be associated with the elevated frequency of endemic myxedematous cretinism in Central Africa. PMID- 2239788 TI - Catabolic effects of high-dose corticosteroids persist despite therapeutic benefit in rheumatoid arthritis. AB - Although corticosteroids (CS) cause nitrogen wasting in healthy humans, it is not known whether the salutary antiinflammatory and appetite-stimulating effects of CS in inflammatory diseases mitigate this effect. We measured nitrogen balance before, during, and after 3 d of high-dose methylprednisolone therapy in nine patients with flare-ups of rheumatoid arthritis. There was evidence of preexisting somatic protein and fat depletion in seven of nine subjects. Patients were allowed to eat freely on a metabolic ward. Nitrogen balances were -0.89 +/- 1.38 g/d (means +/- SEM) before CS therapy, -5.77 +/- 1.30 g/d during therapy (P less than 0.001), and -3.54 +/- 1.38 g/d after therapy (P less than 0.01) despite increased energy and nitrogen intake and clinical resolution of inflammation during and after the pulse therapy. We conclude that patients with rheumatoid arthritis are often cachectic and high-dose CS cause nitrogen wasting in these patients despite an antiinflammatory and appetite-stimulatory benefit. PMID- 2239789 TI - Effects of fish-oil ingestion on cardiovascular risk factors in hyperlipidemic subjects in Israel: a randomized, double-blind crossover study. AB - Effects of a daily fish-oil supplement on serum lipids, apolipoproteins, and some platelet functions and hemorheologic variables were examined in 27 hyperlipidemic subjects in a randomized, controlled, double-blind, crossover fashion with an identically encapsulated vegetable oil serving as the control treatment. Despite the habitual high linoleic acid intake of the study population, significant incorporation of n-3 (omega-3) fatty acids into the serum, platelet, and erythrocyte lipids was observed after the fish-oil supplement. Ingestion of fish oil resulted in a 40% decrease in the triglyceride concentration, a 12% increase in HDL cholesterol, and a significant decrease in plasma viscosity, whereas the vegetable-oil placebo had no significant effect. We conclude that a moderate intake of fish oil (15 g/d) is a feasible treatment for hypertriglyceridemia even in patients with a background of high linoleic acid intake and that it may have a beneficial effect on several cardiovascular risk factors. PMID- 2239790 TI - Self-reported weight and height. AB - The error in self-reported weight and height compared with measured weight and height was evaluated in a nationally representative sample of 11,284 adults aged 20-74 y from the second National Health and Nutrition Examination Survey of 1976 1980. Although weight and height were reported, on the average, with small errors, self-reported weight and height are unreliable in important population subgroups. Errors in self-reporting weight were directly related to a person's overweight status--bias and unreliability in self-report increased directly with the magnitude of overweight. Errors in self-reported weight were greater in overweight females than in overweight males. Race, age, and end-digit preference were ancillary predictors of reporting error in weight. Errors in self-reporting height were related to a person's age--bias and unreliability in self-reporting increased directly with age after age 45 y. Overweight status was also a predictor of reporting error in height. PMID- 2239791 TI - Two-point vs multipoint sample collection for the analysis of energy expenditure by use of the doubly labeled water method. AB - Energy expenditure over a 2-wk period was determined by the doubly labeled water (2H2(18)O) method in nine adults. When daily samples were analyzed, energy expenditure was 2859 +/- 453 kcal/d (means +/- SD); when only the first and last time points were considered, the mean calculated energy expenditure was not significantly different (2947 +/- 430 kcal/d). An analysis of theoretical cases in which isotope flux is not constant indicates that the multipoint method can cause errors in the calculation of average isotope fluxes, but these are generally small. Simulations of the effect of analytical error indicate that increasing the number of replicates on two points reduces the impact of technical errors more effectively than does performing single analyses on multiple samples. It appears that generally there is no advantage to collecting frequent samples when the 2H2(18)O method is used to estimate energy expenditure in adult humans. PMID- 2239792 TI - Height-normalized indices of the body's fat-free mass and fat mass: potentially useful indicators of nutritional status. AB - Expressing fat-free mass (FFM) and body fat mass (BFM) as percentages of body weight or by weight is unsatisfactory. For example, tall patients with protein energy malnutrition (PEM) can exhibit values for FFM and BFM similar to those of shorter well-nourished individuals. To obviate such difficulties, we propose use of height-normalized indices, namely, a FFM index [FFM (kg)/height (m)2, or FFMI] and a BFM index [BFM (kg)/height (m)2, or BFMI]. We calculated these indices in a reference population of 124 healthy young men and in 32 nonobese young men (from the Minnesota Study) before, during, and after experimental semistarvation. When values for FFMI and BFMI falling below the reference cohort's 5th percentile cutoff point were used as a criterion for PEM, these indices, together with basal oxygen-consumption rate, diagnosed PEM in 27 of the 32 Minnesota Study subjects after 12 wk of semi-starvation. These findings indicate that FFMI and BFMI may be useful in nutritional assessment. PMID- 2239793 TI - Evidence for a secular change in obesity, height, and weight among Navajo Indian schoolchildren. AB - A survey measuring heights and weights of 1969 schoolchildren residing on the Navajo Indian Reservation was conducted in 1989. The findings were compared with National Center for Health Statistics (NCHS) reference data and with surveys of Navajo children from 1955, 1968, and 1981. Approximately twice as many children exceeded the 95th percentile of weight-for-age (11.2% of girls, 12.5% of boys) than would be expected for the NCHS reference population. The mean weight-for height z scores exceeded those for the NCHS reference population for all ages in both sexes. Compared with data from 1955, mean heights increased 6.1% among boys and 4.4% among girls whereas mean weights increased 28.8% among boys and 18.7% among girls across all age groups. The data suggest that there has been a secular change in height, weight, and obesity in Navajo Indian children over the past 35 y. PMID- 2239794 TI - Aggressive oral refeeding in hospitalized patients. AB - Malnutrition is an important clinical condition leading to increased morbidity and mortality. This report describes an aggressive oral refeeding program of high caloric foods, which was instituted in severely anorectic patients because of their refusal to eat meals or supplements. After ascertaining a patient's favorite sweet, hospital personnel and family collaborated in providing the food. Frequently, sweets were the patient's only intake for weeks. We saw a gradual return of appetite, inclusion of other foods in the diet, and overall clinical improvement in comorbid conditions. These cases suggest that aggressive oral refeeding with high-caloric foods is an underutilized therapy for multiply impaired elderly patients. PMID- 2239795 TI - Caloric compensation for lunches varying in fat and carbohydrate content by humans in a residential laboratory. AB - Two groups of three subjects participated in a residential study that assessed the effects of varying the macronutrient and caloric content of a required lunch meal on subsequent food choice and intake. Lunches contained 431 or 844 kcal, with the caloric differential created by manipulating the calories derived from either fat or carbohydrate (CHO). Each lunch condition (high-fat, high-CHO, low fat, and low-CHO) was examined for 3 consecutive days. Subjects controlled their own patterns of food intake and could consume any item or number of items at any time during the day or night. There were no significant differences in total daily caloric intake across conditions, indicating that subjects compensated for the caloric content of the lunch regardless of the macronutrient content. Total daily caloric intake under the high-fat and high-CHO conditions was 2824 +/- 151 (mean +/- SEM) and 2988 +/- 187 kcal, respectively, whereas intake under the low fat and low-CHO conditions was 2700 +/- 131 and 2890 +/- 247 kcal, respectively. PMID- 2239797 TI - Energy supplementation in the last trimester of pregnancy in East Java, Indonesia: effect on maternal anthropometry. AB - The effect of prenatal energy supplementation on maternal anthropometry was assessed in a controlled, randomized trial in Madura, East Java. At 26-28 wk of gestation women were either given 465 kcal/d (HE group) or 52 kcal/d (LE group). Two hundred seventy-six women were enrolled in the HE group and 266 women, in the LE group. Supplement intake was variable. Testing of effect by treatment and compliance was thus done by subcategories (HE 1-3 and LE 1-3, corresponding to less than 45, 45-89, and greater than or equal to 90 packets of supplement consumed). Analysis of variance did not show significant differences among the six subcategories in third-trimester weight gain, sum of skinfold thicknesses, 4 wk postpartum weight, or body mass index. In this population energy supplementation for the short duration of the last 90-110 d of pregnancy was not sufficient to improve maternal nutrition as judged by anthropometry. PMID- 2239796 TI - Weight loss and change in resting metabolic rate. AB - The relation between change in resting metabolic rate (RMR) and change in fat free mass (FFM) after weight loss is not well understood and is often inappropriately expressed in kilocalories per unit of FFM. We measured RMR and FFM in 35 obese patients enrolled in a conservative weight-loss program. RMR per kilogram FFM was not different after weight loss. However, the regression of delta RMR on delta FFM revealed that the decline in RMR tended to be greater than could be accounted for by loss of FFM. At initial test and retest, body fat (Fat) was not a predictor of RMR after FFM had been taken into account but delta Fat significantly contributed to the prediction of delta RMR when added to the equation after delta FFM. Thus, people losing larger amounts of weight had declines in RMR greater than could be accounted for by loss of FFM. Self-reported age of onset of obesity was not related to delta RMR. PMID- 2239798 TI - Consumption of food and nutrients by infants in Huascar (Lima), Peru. AB - Consumption of breast milk, liquids, and foods by 131 poor Peruvian infants was measured on 1661 child-days of observation during their first year of life. Breast-milk intake was estimated by 12-h test-weighing; macronutrients were analyzed in samples of milk. Other foods and liquids were weighed at preparation and consumption; nutrient contents were estimated from food composition tables. Mean energy intakes increased with age but declined from 95% to 78% of recommended amounts during the year. Mean protein intakes were generally above recommended amounts but more than one-third of infants received less than 80% of the suggested safe intakes in the second (6-mo) semester. Breast milk was the major source of energy and protein during the first semester. Breast milk and cow milk together contributed more than half the energy and protein during the second 6 mo, when cereals were also an important source of energy and protein. Mean intakes of calcium, thiamin, and ascorbic acid were less than recommended at some ages but mean intakes of other selected micronutrients exceeded recommendations. PMID- 2239799 TI - Diminished survival of young blacks with adenocarcinoma of the prostate. AB - The survival rates of 117 black and white patients treated by primary radiation for carcinoma of the prostate at the State University of New York Health Science Center at Brooklyn and Kings County Hospital Center were analyzed according to age and race. In addition, stage, grade, and delay time in seeking medical attention were analyzed. Survival was similar in both young (less than 60 years) and old (greater than or equal to 60 years) patients, with 45% and 41% 5-year survival rates, respectively. Survival was better in white patients, 48% 5-year survival, than in blacks, 35% 5-year survival. Black patients presented with higher stage disease than whites (p less than 0.01). This trend was even greater in young black males, who had higher grade (64% versus 11%; p less than 0.04) and higher stage tumors (p less than 0.05). In addition, young blacks delayed seeking medical attention greater than 3 months 72% of the time, as compared to 0% in white young males (p less than 0.005). A survival difference was also seen in young blacks as compared with young whites: 3.9-year median survival versus 6.0 year median survival, respectively. PMID- 2239800 TI - Phase II study of vinblastine in previously treated squamous carcinoma of the cervix. A Gynecologic Oncology Group study. AB - Thirty-six patients with advanced squamous carcinoma of the uterine cervix recurrent after radiotherapy or surgery or first-line chemotherapy were eligible for a phase II study employing vinblastine in a dose of 9 mg/m2 intravenously every 3 weeks until disease progression or toxicity supervened. Two patients were never treated, leaving 34 patients evaluable for toxicity. One patient was inevaluable for response, leaving 33 evaluable for this parameter. Thirty-two patients had prior radiotherapy and 30 had prior chemotherapy. All patients had Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2. Median age was 46 years. Twenty patients had disease in the pelvis and 13 had extrapelvic metastases. Fourteen patients had grade 3 lesions. A median of three courses (range: 1-12 courses) was administered. Ten patients (29.4%) experienced GOG grade 3 or 4 leukocytopenia and 10 had grade 3 or 4 granulocytopenia. Other toxicity included grade 4 gastrointestinal toxicity and anemia in one patient each and two patients with grade 3 neurotoxicity. Twenty patients (60.6%) had stable disease with therapy and 13 had increasing disease. No responses were observed. Vinblastine in this dose and schedule is inactive in previously treated patients with squamous carcinoma of the cervix. PMID- 2239801 TI - Phase II study of recombinant alpha-interferon in malignant melanoma. AB - Ninety-seven evaluable patients with measurable, advanced, malignant melanoma were treated with recombinant alpha interferon in a cooperative phase II efficacy trial, whose primary objective was to estimate the response rate. Interferon (rIFN alpha-2a, Roferon-A) was injected subcutaneously daily for 70 days. Dose was escalated in four steps from three million units to 36 million units over ten days. Eight patients responded objectively and six patients (6%) had a complete response. The median duration of complete response was 11 months. Patients achieving complete response had only cutaneous, nodal, or pulmonary disease; some had extensive prior therapy; some could tolerate no more than three million units per day. Few patients could tolerate the target dose of 36 million units daily for 70 days. Limiting toxicity was primarily fatigue. Interferon in tolerable doses is effective in a small subset of patients with melanoma. Comparison of published trials of dacarbazine and recombinant alpha interferon indicates the two drugs have similar activity. PMID- 2239802 TI - Oral carmofur in advanced gastrointestinal cancer. AB - One hundred and twenty-four patients with a diagnosis of metastatic gastrointestinal cancer and no prior therapy were included in this clinical study of carmofur monotherapy, 300-500 mg/m2 daily for 6 weeks. For the 115 evaluable patients, the response rates were 19.4% in gastric cancer, 27.2% in cancer of mobile colon, and 12.5% in rectal cancer. No objective responses were seen in 38 patients with pancreatic cancer, although the disease of 13 of these patients has remained stable over a considerably long period of follow-up. The toxicity profile was interesting; the main adverse effects were urinary bladder symptoms and flush. Hematologic toxicity was minimal. The treatment proved to be safe and could be used for outpatients. PMID- 2239803 TI - 5-Fluorouracil infusion and low-dose weekly cisplatin: an analysis of increased toxicity. AB - It has been suggested that the addition of weekly low-dose cisplatin (DDP) may potentiate the efficacy of continuous infusion 5-fluorouracil (5-FU) without adding significant toxicity. To investigate the extent of added toxicity, an analysis of toxicity was completed in 18 patients with advanced cancers treated with continuous ambulatory 5-FU infusion 300 mg/m2/day and weekly low-dose cisplatin (DDP) 20 mg/m2. Ten of the 18 patients (56%) developed multiple (four or more) toxicities during treatment. In addition, toxicity categorized as severe occurred in 10 patients (56%). Seventeen of the 18 patients (94%) required treatment interruption or dose attenuation due to toxicity and most patients experienced a decline in Eastern Cooperative Oncology Group performance status due to treatment-related toxicity. Compared with historical toxicity patterns when 5-FU infusion is administered alone, the addition of DDP has resulted in significant increases in nausea and vomiting, anorexia, diarrhea, stomatitis, and myelosuppression. The addition of low-dose weekly DDP adds significant toxicity and morbidity to the continuous 5-FU infusion regimen. PMID- 2239804 TI - Angiosarcoma of the forearm definitively treated by hyperfractionated irradiation. AB - A case report of an angiosarcoma treated definitively with hyperfractionated irradiation is presented. Radial and ulnar aspects of the proximal forearm, wrist, and digits were diffusely involved on angiography. Hyperfractionated irradiation totaling 7,440 cGy was delivered to the entire circumference of the hand, forearm, and distal 5 cm of the arm; a confluent dry erythema without moist desquamation was observed at completion of therapy. No significant local or systemic toxicity was noted with the administration of an Adriamycin-containing adjuvant chemotherapy regimen following irradiation. Local regional control at 2 years is documented both clinically and by angiographic examination and the patient otherwise is free of disease. Function remains excellent with no lymphedema or joint fibrosis observed and grip strength of treated and untreated hands is comparable at 35 pounds. For patients refusing amputation or who are otherwise inoperable, hyperfractionated irradiation provides a therapeutic option. PMID- 2239805 TI - Nodular histiocytic lymphoma, emphasizing results of stage I disease treated by radiotherapy. A report of the Japan Lymphoma Radiation Therapy Study Group (JLRTG). AB - The records of 49 patients with nodular histiocytic lymphomas (NH) who were treated from 1972 to 1985 in hospitals belonging to the JLRTG were retrospectively reviewed. The actuarial survival rate and relapse-free survival rate of all patients after 5 years were 55.0 and 51.3%, respectively. Twenty-one patients with stage I disease had a significantly better survival rate than did 12 patients with stage II disease (P less than 0.01). Without combination chemotherapy, all 15 patients with stage I NH treated by radiation therapy were in complete remission, and 14 of them remained alive and well. Among these 15 patients, no difference in relapse was observed between patients who received involved field irradiation (1 of 6) and those who received extended field irradiation (2 of 9). Patients with stage II or more NH should be treated with intensive chemotherapy and radiotherapy, as are patients with diffuse histiocytic lymphoma (DH). However, involved field radiotherapy with careful follow-up observation may be the treatment of choice for patients with stage I NH, provided their tumors are not bulky. PMID- 2239806 TI - Mitoxantrone and constant infusion etoposide for relapsed and refractory acute myelocytic leukemia. AB - In an effort to search for new, synergistic and non-cross-resistant antileukemic regimens, the Cancer and Leukemia Group B (CALGB) investigated the activity and toxicity of mitoxantrone in combination with etoposide for the reinduction of patients with relapsed or refractory acute myelocytic leukemia (AML). Mitoxantrone, 12 mg/m2 daily for 3 days, was combined with three dose levels of etoposide, 100, 150 and 200 mg/m2 daily by constant infusion for 5 days. There were 19 male and 13 female patients, with a median age of 46 (range, 21-74). Of these, nine were primarily refractory to daunorubicin and ara-C; 17 had one prior complete remission (CR), five had two prior CR, and one had three prior CR. Thirteen patients were entered at the first dose level, 11 were entered at the second, and eight at the third. All but one patient, whose death occurred within the first 2 days of treatment, are evaluable for toxicity. There were five CR (four at the first and one at the second dose level) and six partial remissions (PR) (three at the first dose level and three at the second). Unmaintained responses lasted 6-33 weeks. Median survival for all patients was 12.6 weeks. Anti-leukemic effects with severe marrow hypoplasia were observed in all patients; severe nausea and vomiting were seen in four. Severe mucositis, often indistinguishable from superimposed candidiasis, occurred in 40% of all patients; it was associated with dose-limiting esophagitis (three of seven evaluable patients) at the highest etoposide dose. Hepatic and renal dysfunction was severe in three patients; no treatment-related severe pulmonary or cardiac toxicity was observed. Posttreatment infectious complications were severe in 11 patients. In three cases, they were fatal--an incidence not dissimilar from that of other reinduction regimens in heavily pretreated patients. The regimen appears to be active; the combination of mitoxantrone, 12 mg/m2 daily for 3 days, with etoposide, 150 mg/m2/day for 5 days, by constant intravenous infusion is now being explored by the CALGB in a randomized phase II study against mitoxantrone plus diazoquinone and diazoquinone plus etoposide. PMID- 2239807 TI - Hypercalcemia and malignant melanoma. AB - Hypercalcemia is a rare complication associated with malignant melanoma. Three recent cases of patients with malignant melanoma and hypercalcemia are described. PMID- 2239809 TI - Leptomeningeal carcinomatosis. PMID- 2239808 TI - Spontaneous pneumomediastinum in esophageal carcinoma. AB - Although fistulae and hypercalcemia are rare at the time of diagnosis of esophageal carcinoma, they are not uncommon terminal events. Most fistulae communicate with the respiratory tract. Uncommon sites of fistulae due to esophageal carcinoma include extension to the aorta, pleura, pericardium, and mediastinum. We report a patient with a spontaneous pneumomediastinum discovered during radiologic staging of esophageal carcinoma. The symptoms were dysphagia, weight loss, and pneumonia. The patient had hypercalcemia refractory to conventional measures, another adverse prognostic factor. Cisplatin 100 mg/m2 was tolerated without acute toxicity and lowered the serum calcium to normal. However, the patient died due to respiratory failure 2 days after cisplatin therapy. To our knowledge, this is the first report of a spontaneous pneumomediastinum at presentation of an esophageal carcinoma. The course of our patient and a review of the literature suggest that fistulae and/or hypercalcemia are medical emergencies and are often fatal in esophageal carcinoma. PMID- 2239810 TI - Yeuhchukene--an indole derivative interacting with guinea pig reproduction. AB - Natural yuehchukene in doses of 10 mg/kg/day induced a 40% reduction of pregnancies in the guinea pig as compared with controls (p less than 0.05). Yuehchukene also caused a reduction in litter size which, however, was not significant indicating limited toxicity of the drug. An inhibition of ovum fertilization and/or implantation is suggested as the mechanism of action. PMID- 2239811 TI - Protective effect of danshen during myocardial ischemia and reperfusion: an isolated rat heart study. AB - The effect of Danshen (Radix salviae miltiorrhizae) on mechanical activity and coronary flow rate of isolated rat hearts was examined to assess the ability of Danshen to protect the myocardium against the effects of ischemia and reperfusion. After 20 min of control perfusion, in the presence or absence of Danshen, the hearts were made totally ischemic for 30 min and then reperfused for 30 min. Danshen had a negative inotropic effect and caused an increase of coronary flow rate. During post-ischemic reperfusion recovery of left ventricular developed pressure in the Danshen-treated hearts was significantly better and contracture was significantly less than in the untreated hearts. The results indicate that Danshen protects the heart against some of the deleterious effects of ischemia and reperfusion. PMID- 2239812 TI - Long-term reno-cardiovascular effects of orally administered aconiti tuber in humans. AB - The reno-cardiovascular effects of Aconiti Tuber were studied. In a controlled, double-blind, and randomized clinical trial, it was found that in 9 months, Aconiti Tuber, after preparation (120 degrees C, 40 min), (1) had no apparent adverse effects, (2) showed positive inotropic, positive chronotropic, and vasodilator effects, (3) increased renal blood flow, and glomerular filtration rate, Na+/Cl-/K+ excretions. The renal function test results could be interpreted as secondary to hemodynamic changes. We conclude that specially prepared Aconiti Tuber may be a promising cardiotonic agent. PMID- 2239813 TI - Medicinal plants used for the treatment of hepatitis in Taiwan. AB - In an extensive ethnobotanical survey of the folk medicines of Taiwan, 69 kinds of crude drugs and 107 species of medicinal plants were found to be used for hepatitis treatments. The present paper is to update a list of medicinal plants used in the treatment of hepatitis and evaluate their liver protection by ethnopharmacological and pathological studies. Results show that some of these drugs have prominent therapeutic effects. Further investigation regarding the anti-hepatotoxic principles will be made. PMID- 2239814 TI - Effects of sairei-to on the relapse of steroid-dependent nephrotic syndrome. AB - Sairei-To (Chai-Ling-Tang) was administered to four patients with steroid dependent relapsing nephrotic syndrome. It was associated with prednisolone and immunosuppressive agents. Histological diagnosis was minimal change in three patients and mild focal glomerulonephritis in one patient. After the start of Sairei-To administration the relapse was markedly suppressed in three patients but not at all in the other. Although we could consider Sairei-To effective for steroid-dependent nephrotic syndrome in the present study, a larger study is necessary to confirm its efficacy. PMID- 2239815 TI - Effects of a medicinal herbal liqueur, "yomeishu", on post-operative gynecological patients. AB - We administered 20 ml of Yomeishu (YMS) twice a day before meals for 12 weeks to 50 post-operative patients in gynecology and then inquired into their subjective 20 symptoms (sense of fatigue, insomnia, headache and heavy headedness, appetite, stomach-ache, abdominal inflation, vertigo, lumbago, etc.) The YMS group showed a significant improvement on 14 items compared with the control group. On the whole, a great improvement was observed in the YMS group with serious subjective symptoms as well, and there were significant differences for general condition, sense of fatigue, and coldness in extremities. PMID- 2239816 TI - Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr.) Karst after X-ray irradiation in mice. AB - Six to seven week old male mice of ICR strain were exposed to 500 or 650 cGy of X ray during experiments to determine if Ganoderma lucidum could be a factor in modification of radiation damage. Continuous intraperitoneal injection of the extract from Ganoderma lucidum before or after irradiation of 500 and 650 cGy of X-ray was found to improve the 30-day survival fractions of ICR mice, but wasn't significant by statistical analysis. The administration also enhanced the recoveries of the body weights and increased the recovery of hemograms of irradiated mice from radiation damage by injecting before or after radiation exposure, especially for the treatment of 500 cGy irradiation. The 10-day CFUs was significantly higher for Ganoderma lucidum treated groups than for untreated groups. However, the differences of radioprotective effect between the X-ray irradiated groups with Ganoderma lucidum pretreated and post-treated were not significant (p greater than 0.05). PMID- 2239817 TI - Effect of khatamines and their enantiomers on plasma triiodothyronine and thyroxine levels in normal Wistar rats. AB - The effect of cathinone and N-formylnorephedrine, two psychoactive amines of khat (Catha edulis Forsk.) and their enantiomers have been studied on plasma levels of triiodothyronine (T3) and thyroxine (T4) in male Wistar rats. The rats were injected with 5, 10 and 30 mg/kg, body weight of four khatamines and the blood samples were collected 2 h after their administration. In the separate set of experiments the effect of these khatamines at 1, 2 and 4 h after their administration was also examined. All the khatamines failed to produce a significant dose dependent increase in T3 and T4 levels in the dose of 5 mg/kg. However, all of these compounds produced a significant dose dependent increase in T3 and T4 levels at higher doses but only T4 levels were increased following the dose of 10 mg/kg. Our studies on the effect of khatamines in T3 and T4 levels at various times showed a significant increase in T4 levels in all the four groups treated with various khatamines and the peak effect was observed at 2 h in case of (-)- and (+)-cathinone and 4 h in case of (-) and (+)N-formylnorephedrine. This study suggests that the symptoms observed in khat chewers including hyperthermia, anorexia, and metabolic changes may to some extent be attributed to the thyroid stimulating effect of khatamines. However, further studies are needed to establish the mechanism of release of thyroid hormones by these compounds and their involvement in the pharmacological effects. PMID- 2239818 TI - Effects of single and multiple moxibustions on activity of platelet function, blood coagulation and fibrinolysis in mice. AB - The effects of single and multiple moxibustions on platelet function, blood coagulation and fibrinolytic activity in ddY mice were studied. The increase in platelet aggregation and ATP-release after a single moxibustion was dependent on moxa weight and the kind of platelet stimulus. Blood coagulative activity tended to increase in the early phase after a single moxibustion. However, multiple moxibustions maintained the homeostasis on blood coagulation and fibrinolytic activity. This investigation suggests that the effects of moxibustion on platelet functions and coagulative and fibrinolytic activities cause an enhancement of the phagocytic activity in the host defense mechanism. PMID- 2239819 TI - Follicular neoplasms of the thyroid in men older than 50 years of age. A DNA flow cytometric study. AB - The clinical behavior of follicular neoplasms of the thyroid in elderly men can be difficult to predict on histologic grounds alone. To assess the usefulness of DNA flow cytometry in predicting the metastatic potential of these tumors, the authors studied 44 primary and metastatic follicular neoplasms of the thyroid by DNA flow cytometry of paraffin-embedded tissue. The neoplasms were obtained from 44 men ranging in age from 50 to 79 years (mean, 60). There were 29 follicular adenomas, 11 primary follicular carcinomas (neoplasms with capsular and/or vascular invasion), and 4 metastatic follicular carcinomas. Follow-up information was available on 40 of the 44 patients. The mean follow-up was 114 months. Twenty five of the 29 follicular adenomas had a diploid DNA content, 2 (7%) were tetraploid, and the DNA histograms on 2 were not interpretable. All patients with follicular adenomas had no evidence of disease (NED) at last follow-up. Eight of the 11 primary follicular carcinomas were diploid. Six of these patients had NED, one died with carcinoma at 82 months, and no follow-up was available on one. Three (27%) of the primary follicular carcinomas were aneuploid or tetraploid. Two of these patients had NED, and the third died with carcinoma 84 months after diagnosis. Two of the four metastatic follicular carcinomas were diploid and two (50%) were aneuploid or tetraploid. One of the two patients with diploid metastatic follicular carcinomas died with carcinoma, as did one of the two patients with aneuploid metastatic follicular carcinomas. These results suggest the following: (1) follicular carcinomas are more likely to be aneuploid or tetraploid than are follicular adenomas; (2) follicular neoplasms without capsular or vascular invasion may include a small number of aneuploid or tetraploid tumors; and (3) DNA ploidy does not add to the prognostic value of histologic studies alone. PMID- 2239821 TI - Improved flow cytometric determination of proliferative activity (S-phase fraction) from paraffin-embedded tissue. AB - Recent studies suggest that proliferative activity (S-phase fraction [SPF]) may have greater prognostic significance than total nuclear DNA content; however, relatively few studies have examined SPF from paraffin-embedded tissue because of significant contamination of histograms with debris. In this study, cell cycle analysis was performed on 124 matched tissue specimens. Fresh tissue was divided into two equal portions; one portion was frozen, whereas the other portion was processed and embedded in paraffin. S-phase could be determined for both frozen and paraffin-embedded tissue in 81 cases. Correlation between SPF from frozen and paraffin-embedded tissue was demonstrated (r = 0.80) when debris was subtracted from histograms with the use of two new subtraction algorithms referred to as multicut and singlecut. Unlike other debris-subtraction algorithms, the quantity and distribution of debris calculated by these algorithms are dependent on the magnitude and position of histogram peaks. A lesser degree of correlation was demonstrated with the use of a standard exponential debris subtraction algorithm (r = 0.67). Correlation of SPF for aneuploid cases was greater when SPF was calculated as a percentage of the aneuploid cell population rather than as a percentage of the entire cell population. This was attributed to the observation that the proportion of aneuploid cells from paraffin-embedded tissue was less than that from frozen tissue. The results of this study indicate that SPF can be calculated from paraffin-embedded tissue with values comparable to those obtained from frozen tissue. The ability to calculate SPF reliably from paraffin-embedded tissue should allow additional evaluation of this parameter as a prognostic indicator. PMID- 2239820 TI - Inflammatory myofibroblastic tumor (plasma cell granuloma). Clinicopathologic study of 20 cases with immunohistochemical and ultrastructural observations. AB - Twenty cases of inflammatory myofibroblastic tumor (IMT) were studied; 19 involved the lung and 1 the esophagus only. The patients' ages ranged from 3 to 72 years. There were 9 males and 11 females. Involvement of a bronchus was seen in one case and of mediastinal structures in four. Chest pain and dyspnea were common symptoms; eight patients were asymptomatic. Seven patients underwent lobectomy, 12 local excision, and 1 biopsy alone. The lesions were nonencapsulated and ranged from 1.2 to 15 cm. Various proportions of plasma cells, histiocytes, and spindle cells were observed; the latter corresponded ultrastructurally to fibroblasts and myofibroblasts, were immunoreactive for vimentin and actin and focally for desmin, and were negative for epithelial markers. Plasma cells were polyclonal for light chains. One patient had two recurrences, and in one case a large pleural IMT was found eight years after the excision of a similar lesion in the lung. All patients with follow-up (ten) were well as long as ten years after the diagnosis (average, 3.7 years). PMID- 2239822 TI - Immunophenotypic aberrancy in adult acute lymphoblastic leukemia. AB - Some recent reports indicate a high frequency of immunophenotypic aberrancy in acute lymphoblastic leukemia (ALL). To investigate this issue with regard to adult ALL, the authors reviewed the immunophenotyping data from 39 cases analyzed in their clinical laboratory. Flow cytometric analysis of peripheral blood and/or bone marrow was performed with the use of a panel of 21 B-cell, T-cell, and myeloid monoclonal antibodies (MoAbs). The surface antigen profiles of the leukemic cells were compared with those of normal bone marrow and thymic counterparts, as defined by current models. Twenty-six cases were B-precursor ALL, 8 were T-ALL, and 3 were B-ALL (Burkitt's leukemia). Only two cases coexpressed lymphoid and myeloid antigens. In contrast, intralineage aberrancy was quite common. Immunophenotypes from 13 of 26 B-precursor ALL cases deviated from normal B-lineage marrow cells as defined by a recent classification. The T ALL cases were also immunophenotypically heterogeneous. This high incidence of aberrant antigen expression in adult ALL suggests that leukemogenesis also involves aberrant differentiation rather than purely a process of maturational arrest. PMID- 2239823 TI - Comparison of DNA and karyotype aneuploidy in malignant lymphomas. AB - Tumors from 48 patients with non-Hodgkin's lymphoma were examined for flow cytometric DNA ploidy and chromosome constitution to determine the degree of concordance of these two methods. Histologically, there were 24 low-grade, 19 intermediate, and 5 high-grade lymphomas. Flow cytometry revealed an aneuploid cell population in 19% of the cases. The mean DNA index of the aneuploid tumors was 1.58 +/- 0.71. The frequency of DNA aneuploidy was only slightly higher (23%) in intermediate than in low-grade lymphomas (17%). None of the five high-grade lymphomas showed DNA aneuploidy. The chromosome study was successful in 81% of cases (39 of 48), and clonal chromosome abnormalities were observed in 92% of these (36 of 39). In most of the chromosomally abnormal clones the chromosome number was in the diploid range. Most tumors with pseudodiploid (46 chromosomes), hypodiploid (45-44 chromosomes), or hyperdiploid (47-49 chromosomes) clones were DNA diploid by flow cytometry. On the other hand, all specimens with a chromosome number exceeding 50 were DNA aneuploid by flow cytometry. Therefore, flow cytometric DNA analysis appears to be a rather coarse method that will detect aneuploidy only when there is a major increase in chromosome material. PMID- 2239824 TI - Antinuclear matrix antibody. Hidden antinuclear antibody in patients with connective tissue diseases. AB - A total of 435 serum samples from patients with different rheumatic diseases were screened for the presence of autoantibody to nuclear matrix components by indirect immunofluorescence on 0.1 mol/L HCl extracted HEp-2 cell and WiL2 cell substrates. A total of 28 specimens were positive in this assay. Eighteen of them were from patients with systemic lupus erythematosus (18 of 250), 2 from patients with rheumatoid arthritis (2 of 115), and 8 from patients with mixed connective tissue disease (8 of 10). Antigenic material for this antibody is resistant to DNase, partially sensitive to RNase, and sensitive to trypsin. This indicates that the antigen is composed of protein and possibly RNA. In immunoblot analysis, sera positive for this antibody in indirect immunofluorescence assay recognized different peptides. This suggests that protein peptides are the major antigenic material. PMID- 2239825 TI - Measuring platelet aggregation with microplate reader. A new technical approach to platelet aggregation studies. AB - Platelet aggregation measurements were done with the use of a commercially available microtiter plate reader with specific modification of the mode of agitation of the samples. Satisfactory aggregation curves were obtained with use of an external horizontal agitator, with an amplitude of 1.3 mm and minimum frequency of 1,360 cycles/minute. With the use of the 96 available wells in the microtiter plates, all test and control platelet samples, with replicates, were observed simultaneously and the output data obtained within 10-15 minutes. The technique was validated by demonstrating the similarity of dose-response curves, obtained with a standard aggregometer and with the microtiter technique, of platelets stimulated by adenosine diphosphate, thrombin, and arachidonic acid. PMID- 2239826 TI - The effects of radioisotopes used in nuclear medicine on diagnostic radioimmunoassay testing. Is there any significant interference? AB - The administration of radioisotopes for diagnostic nuclear medicine scans and therapeutic procedures is quite prevalent today. A period of interference with the counting of a radioimmunoassay [RIA] test may occur with the serum of a patient receiving an in vivo radionuclide that decays by gamma emission. Because the logistics of precounting all specimens may be cumbersome and prohibitive, it is important to determine the degree of this interference. In this study, the authors evaluate the potential interference of the most commonly used radioisotopes with RIA studies. For two months (March and August 1988) 10,650 patient serum specimens were counted for significant background gamma radiation before RIA testing. Forty-three patients, on whom 105 RIA tests were performed, were identified as having preassay gamma radiation in their serum. With the use of selective energy windows for each different interfering radionuclide, proportional determinations were made as to the amount of interfering gamma radiation spilling into the iodine 125 test marker window. It was shown that initial whole serum pretest gamma counts as high as 111,000 counts/minute did not significantly affect the results of the RIA. Because of the meticulous washing and decanting procedures required in modern RIA and the monoclonal nature of most antibodies used currently, it appears the degree of nonspecific binding of this potentially interfering radiation is minuscule. The energy level of cobalt 57, however, and many of the other commonly used radioisotopes, overlaps so closely that it is difficult to window for this interference. It is possible, therefore, that this distinction cannot be made and folate and vitamin B12 test systems using cobalt 57 markers may have to be routinely prescreened. The authors conclude that the requirement for prescreening of all RIA test samples for interfering gamma radiation is unnecessary (1987 CAP Commission on Laboratory Accreditation Inspection Checklist, Section VII, Question 07.0290). PMID- 2239827 TI - Microstaging of squamous cell carcinomas. AB - The clinical classification of squamous cell carcinoma, which was established primarily by the International Union Against Cancer (UICC), does not permit optimal estimation of expected metastasis. The authors' results indicate that metastasis can be more accurately estimated on the basis of invasion depth, histopathologic grading, and especially tumor thickness. One essential advantage of these criteria is that they can be established by a histopathologist. It is interesting to note that in the authors' collective no carcinoma less than 2 mm thick metastasized, that is, a relatively high percentage of carcinomas (48%) can be graded as no-risk carcinomas. The risk of metastasis for undifferentiated carcinomas greater than 6 mm thick that have infiltrated the musculature, the perichondrium, or the periosteum, however, is quite high. Tumors between 2 and 6 mm thick with moderate differentiation and a depth of invasion that does not extend beyond the subcutis can be classified as low-risk carcinomas. PMID- 2239828 TI - Histiocytosis X. S-100 protein, peanut agglutinin, and transmission electron microscopy study. AB - Twenty-seven cases of histiocytosis X (HX) for which paraffin blocks were available were studied with the use of S-100 protein immunohistochemistry, peanut agglutinin affinity histochemistry, and transmission electron microscopy. The results show that these techniques did enable identification of Langerhans'-type histiocytes in 88.5%, 75%, and 47.4% of cases, respectively. All techniques were proved to be of some diagnostic value for HX, but none was able to confirm the diagnosis in all instances and none could foretell the prognosis of the patients. This study shows that besides the Langerhans' cells, the indeterminate cells of the skin and the interdigitating dendritic reticulum cells of the lymph node may also be involved in this process. Moreover, some multinucleate giant cells and foamy cells may be derived from Langerhans' and related cells. PMID- 2239830 TI - On the microstaging of skin cancer. PMID- 2239829 TI - Primary malignant melanoma of the lower respiratory tract. Report of a case and literature review. AB - The authors report a case of primary bronchial malignant melanoma, occurring in a 34-year-old woman presenting with persistent cough. At bronchoscopic examination, a polypoid mass was found to occlude the left mainstem bronchus. Biopsies showed a malignant epithelioid tumor resembling an atypical carcinoid. Histochemistry, electron microscopic study, and immunohistochemistry confirmed the diagnosis of melanoma. Physical examination and additional clinical history to exclude other possible primary sites were negative. The patient underwent thoracotomy with left pneumonectomy. Nineteen months after resection she was found to have a histologically similar tumor involving her left adrenal gland. Review of the literature shows that melanoma of the lower respiratory tract has been reported only in adults and has a tendency to present as a central polypoid growth that may be responsive to surgical resection. PMID- 2239831 TI - Estimating the clinical usefulness of diagnostic tests. PMID- 2239832 TI - Detection and monitoring of Bence Jones proteinuria. PMID- 2239833 TI - Extraovarian transitional cell carcinoma of female genital tract. PMID- 2239834 TI - The Albert H. Ketcham Memorial Award. PMID- 2239835 TI - The James E. Brophy AAO Distinguished Service Awards. PMID- 2239836 TI - Auxiliary springs in continuous arch treatment: Part 1. An analytical study employing the finite-element method. AB - This report describes the results of a finite-element analysis with ANSYS (Version 4.3) from Swanson Analysis Systems and 1 mm-long, 2-D elastic beam elements to modify and refine the designs of maxillary and mandibular springs for space-closure management. This system permitted static analysis by means of modern software systems instead of expensive and cumbersome mechanical bench studies. Our examination of anterior and posterior reactions led to what we believe are optimal designs with clinically manageable moment/force ratios and new canine brackets that accommodate these springs within the framework of conventional and straight-wire appliance systems. Three degrees of freedom were used at each node for translations in the x and y directions and a rotation about the z axis, producing 182 elements with 183 nodes for the mandibular model and 146 elements with 147 nodes for the maxillary model. Elgiloy retraction spring models (0.1650 inch x 0.02150 inch) in the edgewise mode were developed so that the effects of three different preactivation bends could be refined by computer analysis. Sixty-four analyses were performed for each spring, with each of three angle bends (theta 1, theta 2, and theta 3) varied from 0 degrees to 45 degrees in 15 degrees increments. The employment of this computer method promises to simplify the design and development of complex interacting orthodontic systems. Clinical cases are presented in Part 2 of this series, which illustrates the application of auxiliary springs. PMID- 2239838 TI - The effect of hydrogen ion concentration on the force-degradation rate of orthodontic polyurethane chain elastics. AB - The effect of pH on the force-degradation rates of seven commercial orthodontic polyurethane chain elastics was evaluated in an in vitro study. The pH values of 4.95 and 7.26 were selected for testing because they represent values close to the reported extremes of plaque and saliva pH. Seven test elastic products were extended to (1) equal distances and (2) equal initial force levels, and the force degradation rates were recorded over 4 weeks. All the test products yielded a significantly greater force-decay rate in the basic (pH 7.26) solution than in the acidic (pH 4.95) solution over 4 weeks. A hypothesis is presented that the decay rate of orthodontic polyurethane chain elastics is inversely proportional to the oral pH, with a corollary that basic pH levels are most hostile to polyurethane chain elastics. PMID- 2239837 TI - Frictional resistance of ceramic and stainless steel orthodontic brackets. AB - Frictional resistance of orthodontic appliances is recognized by most clinicians to be detrimental to tooth movement. The purpose of this study was to compare planar, static frictional forces among stainless steel and ceramic brackets. Both nitinol and stainless steel rectangular arch wires were passed freely through the slots of a pair of brackets from each type. Tests were carried out in air and in artificial saliva. A 300-gm load was suspended from the arch wire to simulate the normal force, and an incremental horizontal force was applied until movement of the arch wire was initiated. Under all conditions, the stainless steel brackets had lower coefficients of friction than the ceramic brackets. The stainless steel wire generated less friction than nitinol, and friction increased in the presence of artificial saliva in comparison with air alone. These results show that, under experimental conditions, ceramic brackets, nitinol arch wires, and saliva all increase static frictional resistance. PMID- 2239839 TI - Sterilization of orthodontic instruments and bands in cassettes. AB - The purpose of this study was to determine whether orthodontic instruments and bands contaminated with blood or saliva and bacterial spores can be heat sterilized while contained in OMS-ASAPsys instrument and band cassettes. Hinged and nonhinged instruments and bands were contaminated and dried, placed in the cassettes, ultrasonically cleaned, rinsed, and dried. The cassettes were wrapped and then processed through standard steam, chemical vapor, or dry-heat sterilizing cycles. Each instrument and band was then cultured for the presence of live spores. The results showed that the residual spores on the instruments and bands after ultrasonic cleaning and rinsing had indeed been killed in all cases. The three types of sterilization were equally effective. The results indicate that contaminated orthodontic instruments and bands can be sterilized within OMS-ASAPsys cassettes. PMID- 2239840 TI - Effects of etchant concentration and duration on the retention of orthodontic brackets: an in vivo study. AB - Etching of enamel before the bonding of orthodontic attachments is usually done with a solution of 37% H3PO4 for 60 seconds. The purpose of this study was to evaluate the effects of etchant concentration and duration on the clinical retention of bonded orthodontic attachments. Two randomly selected groups of orthodontic patients participated in the study. In both groups, teeth in contralateral quadrants, excluding the molar teeth, were bonded. In the first group, 158 teeth were etched with a solution of 37% H3PO4 for 60 seconds, and 155 teeth were etched with 37% H3PO4 for 15 seconds. In the second group, 196 teeth were etched with 37% H3PO4 and 196 teeth with 15% H3PO4, both for 60 seconds. Conventional edgewise mechanotherapy was used in both groups of patients. After 24 months of treatment, in the first group, 8 brackets were dislodged when etched with 37% H3PO4 for 60 seconds and 9 when etched with 37% H3PO4 for 15 seconds. In the second group, 6 brackets were dislodged when etched with 37% H3PO4 for 60 seconds and 13 were dislodged when etched with 15% H3PO4 for 60 seconds. Reducing the etching time of 37% H3PO4 from 60 seconds to 15 seconds or reducing the acid concentration from 37% to 15% H3PO4 applied for 60 seconds had no significantly different effect on the retention of bonded orthodontic attachments. The results suggest that the reduction of etchant concentration and the duration of etching in orthodontic bonding should be considered. PMID- 2239842 TI - A comparison of results of second molar and first premolar extraction treatment. AB - The purpose of this study was to examine treatment results of maxillary and mandibular second molar extraction cases and compare them with treatment results of maxillary and mandibular first-premolar extraction cases. Records of 22 maxillary and mandibular second-molar extraction cases and 22 maxillary and mandibular first-premolar extraction cases were evaluated. For each case, pretreatment and posttreatment lateral cephalograms were traced and several cephalometric parameters were compared. From the pretreatment and posttreatment panoramic radiographs, angulations of the maxillary and mandibular third molars were evaluated. Average treatment time, in months, was recorded for both groups. The data obtained from each group were analyzed for statistical difference. The results showed that the two groups had fewer differences than indicated by advocates of second-molar extractions. Analysis of the cephalometric data demonstrated only a few statistical differences between the groups. The maxillary and mandibular incisors in the premolar group were retracted a significantly greater amount than in the second-molar group. The maxillary and mandibular first molars were protracted a greater amount in the premolar group than in the second molar group. The lower lips in the premolar group were retracted a greater amount than in the second-molar group. The resulting facial profile after extraction of second-molars appears to be no different from that obtained after extraction of first premolars. The pantographic evaluation of the changes in third-molar angulation were not statistically different. In both groups, the maxillary third molars showed an improvement in third-molar angulation, while the mandibular third-molars showed an undesirable increase in angulation. The average treatment time for both groups was not statistically different. PMID- 2239841 TI - Influence of vertical growth pattern on faciolingual inclinations and treatment mechanics. AB - Control of faciolingual tooth inclinations is obtained by using rectangular wire with third-order bends and standard edgewise brackets or by using a straight wire in a preadjusted appliance system. Ideal faciolingual inclinations have been determined previously by measuring facial surface contours relative to coronal long axes. This study evaluates faciolingual inclinations based on occlusal table inclinations relative to occlusal planes. The samples compared include untreated ideal occlusions and malocclusions in three different vertical skeletal growth patterns. Faciolingual inclinations of first molars and central incisors were measured relative to the occlusal plane and to selected cephalometric angular measurements. Statistical comparisons between groups revealed significant differences in the inclinations of the upper incisor relative to the occlusal plane (U1-OP) and the inclination of the occlusal plane relative to sella nasion (OP-SN). No statistically significant intergroup differences were found in the inclination of the lower incisor relative to the occlusal plane (L1-OP) or in the faciolingual inclinations of the maxillary and mandibular first molars. On the basis of the large intergroup differences in the mean angle between the occlusal plane and sella nasion (OP-SN), the use of straight-wire appliance therapy is discussed in terms of the potential for creating differential moments. Because differential moments may facilitate or hinder treatment goals, the practitioner must know the biomechanical sequelae resulting from occlusal plane-sella nasion variations, which differ from normative values when preadjusted brackets are used. PMID- 2239843 TI - The stability of the arch-expansion effects of Frankel appliance therapy. AB - To assess the long-term stability of the arch expansion effects of the functional regulator, mandibular dental casts were evaluated for treatment and postretention changes in intercanine width, width between first premolars, width between second premolars, intermolar width, incisor irregularity, and arch length. This study was comprised of 11 cases that were treated with the Frankel appliance (mean = 27 mo.) and were and average of 4 years and 4 months out of active treatment. Results showed overall stability to be good, with some variability present in individual responses. Intercanine width, width of first premolars, width of second premolars, and intermolar width all demonstrated maintenance of treatment increases. Correction of incisor irregularity displayed better stability than has been reported in other stability studies. Arch length decreased with treatment and continued to decrease during the postretention period, although to a lesser extent than has been previously reported. The results of this study support the statements of Frankel concerning the stability of this type of arch expansion. PMID- 2239844 TI - Increase in vertical dimension by interpositional bone grafts and subsequent craniofacial growth in adolescent monkeys. AB - The purpose of this study was to investigate the relationship between craniofacial growth and total maxillary osteotomy in adolescent Macaca fascicularis monkeys. The monkeys' facial height was increased with the help of interpositional bone grafts. Four monkeys underwent surgical procedures, and five served as controls. The changes in growth after surgery were then assessed with the help of conventional cephalometry and osseous implants. Lateral cephalometric radiographs of all monkeys were taken before and immediately after implant placement, immediately after surgery, and every 4 weeks thereafter for 1 year. Analysis of the cephalometric head films revealed that the increases in facial height assisted by interpositional grafts were not stable. Postsurgical observations showed a relapse in total facial height. PMID- 2239845 TI - Humoral immune response to active root resorption with a murine model. AB - A depression in autoantibody titers to tooth root antigens has been shown to coincide with active root resorption in the dog. Since a murine model would facilitate immunologic studies of root resorption because of the availability of syngeneic and immunodeficient strains, the objectives of this study were to develop a quantitative mouse model for root resorption and to determine if a similar drop in tooth root autoantibodies coincides with active root resorption in this species. Uniform areas of necrosis were created in the periodontal ligaments of lower incisors of 36 male Swiss albino mice by inserting a cryoprobe through a skin incision (-80 degrees C; 5 minutes). Contralateral incisors served as controls. At 0, 3, 5, 7, 10, 14, and 21 days; six mice were killed, and blood and incisors were collected. Relative surface areas of root resorption were quantified with micrographs taken at a standardized position, tilt, and magnification with a scanning electron microscope. Serum autoantibody titers were determined with an enzyme-linked immune sorbent assay with antigen prepared from a 5 mol/L guanidine-HCl-EDTA (pH 5.0) extract of incisor roots that were harvested from syngeneic mice. ANOVA and the paired Student t test were used to compare data at the various time points. No root resorption was evident on control teeth. Localized lesions on treated teeth were found to be of significant size between 7 and 14 days (p less than 0.05), but most of these erupted into the mouth by 21 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239846 TI - Loss of root length and crestal bone height before and during treatment in adolescent and adult orthodontic patients. AB - It is broadly documented that orthodontic tooth movement enhances the risk of apical root resorption and loss of alveolar crestal bone height, but virtually all studies have focused on the conventional adolescent patient. In this study, samples from adolescent and adult patients were matched for sex, malocclusion, and treatment regimen. In-treatment changes in root length were the same for both groups, whereas loss of crestal bone height was somewhat greater in adults. Major differences, however, were found at the start of treatment: Adults (mean = 28 years) had significantly shorter roots and greater alveolar recession than the young teenagers (mean = 12 years). Consequently, treatment per se does not place adults at greater risk; it is the involvement extant at the start of mechanotherapy that merits careful evaluation. PMID- 2239847 TI - An American Board of Orthodontics case report. A nonsurgical and nonextraction approach in the treatment of a skeletal and dental Class III malocclusion in a growing patient. AB - This case report is presented following the specifications of the American Board of Orthodontics. The patient had a true maxillary retrognathism, a mandibular prognathism, and a lower anterior height deficiency. She was treated with a fixed orthopedic appliance, fixed orthodontic appliances, and intermaxillary elastics. [This case was presented to the American Board of Orthodontics in partial fulfillment of the requirement for the certification process conducted by the Board. PMID- 2239848 TI - Legal aspects of orthodontic practice: risk management concepts. Developing protocols for adult patients. PMID- 2239849 TI - Education concerning whiplash shaken infant syndrome: an unmet need. PMID- 2239850 TI - Neonatology blues. PMID- 2239851 TI - Blue sclerae and iron deficiency. PMID- 2239852 TI - Education concerning Whiplash Shaken Infant Syndrome: an unmet need. PMID- 2239853 TI - Human immunodeficiency virus infection and pregnancy outcome in intravenous drug users. PMID- 2239854 TI - Follow-up of calcium and phosphorus homeostasis in preterm infants who are not extremely ill. PMID- 2239855 TI - Transient changes in neuroimaging appearances of the brain following cardiopulmonary bypass. PMID- 2239856 TI - Racial, social, and environmental risks for childhood asthma. AB - Unlike a number of childhood problems, it is not clear that there are racial or socioeconomic disparities in the prevalence of childhood asthma. We analyzed data from the Child Health Supplement to the 1981 National health Interview Survey, a population-based survey with information concerning 15,416 children, to address the following questions: are there racial or socioeconomic differences in rates of childhood asthma; if yes, what is the contribution of social and environmental characteristics to the observed differences? In this sample, black children were more likely to have asthma than were white children (4.4% vs. 2.5%). Racial disparities in prevalence emerged early and at all childhood ages were due to higher black rates of onset between the ages of 1 and 3 years. Poverty status, maternal cigarette smoking, large family size, smaller size of home, low birth weight, and maternal age younger than 20 years at the child's birth were all associated with increased rates of childhood asthma. When available social and environmental characteristics were controlled for using multivariate analyses, the increased risk for asthma among black and poor children was reduced to statistical insignificance. We conclude that black and poor children in the United States do have higher rates of asthma, that social and environmental factors exert substantial influences on rates of asthma, and that much of the racial and economic disparity in prevalence can be accounted for by a variety of social and environmental characteristics. PMID- 2239857 TI - Bacteremia in an ambulatory setting. Improved outcome in children treated with antibiotics. AB - We undertook a study of 414 bacteremic patients (167 with Haemophilus influenzae and 247 with Streptococcus pneumoniae bacteremia) to evaluate their clinical presentation, laboratory and clinical results, and subsequent outcomes. Patients with H influenzae bacteremia were more likely to have soft-tissue foci, poorer clinical appearance at presentation, and be at higher risk for subsequent serious focal infections, persistent bacteremia, and subsequent hospital admissions than patients with S pneumoniae. Patients with H influenzae bacteremia had a 21.1-fold increase in risk of meningitis (95% confidence interval [CI] of 3.8 to 78.0) compared with those with S pneumoniae. The odds ratio for initial lumbar puncture was 5.25 (95% CI [1.1-23.6]). Ambulatory patients treated with antibiotics at presentation were less likely to develop new serious soft-tissue infections, persistent bacteremia, or to require subsequent hospital admissions than untreated patients. The effect of treatment was greater for patients with S pneumoniae than those with H influenzae. Careful follow-up and reevaluation of patients with presumptive bacteremia is essential because treated and untreated patients can still develop serious soft-tissue infections. PMID- 2239859 TI - Diagnostic guidelines for Kawasaki disease. American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease. PMID- 2239858 TI - Total and differential leukocyte counts in clinically well children. Information or misinformation? AB - To determine whether the total and differential leukocyte count is of value as a case-finding test, we applied the evaluation criteria developed by the US Preventive Services Task Force. The criteria comprise review of the current burden of suffering of the disease to be prevented, the attributes of the intervention to be used, and the quality of the evidence available. A literature search revealed no evidence in the form of data from patients, so a chart review of all complete blood cell counts ordered during a 1-year period by one group of pediatricians was undertaken. At least one value outside of published normal ranges was found on 74.7% of the tests performed on clinically well children. No unsuspected illness was discovered as a result of an abnormal total and differential leukocyte count. PMID- 2239860 TI - Childhood deaths from toy balloons. AB - We describe four children who died of suffocation by rubber balloons in Canada between 1983 and 1988. In the United States, at least 121 children have died in a similar manner in the 15 years between 1973 and 1988 according to a report by the US Consumer Product Safety Commission. Although the highest mortality occurred among infants, 30 (25%) of the 121 deaths occurred in children 6 years of age or older. Balloons account for 43% of the approximately 15 childhood deaths related to children's products that are documented each year by the Consumer Product Safety Commission. Toy rubber balloons are thus the leading cause of pediatric choking deaths from children's products. Preventive efforts should be directed toward a ban on this type of balloon and the development of safer alternatives. Meanwhile, public information campaigns should alert parents, physicians, and policymakers to the dangers of toy rubber balloons. PMID- 2239861 TI - Disproportionate septal hypertrophy associated with erythroblastosis fetalis. AB - We retrospectively reviewed clinical and echocardiographic data on 10 newborns with erythroblastosis fetalis who were admitted to our nurseries between 1984 and 1988 and who required a double-volume exchange transfusion and neonatal intensive care. Echocardiograms were performed in the first 48 hours of life. In 5 patients, disproportionate septal hypertrophy was demonstrated; 1 additional patient had biventricular hypertrophy with a thickened septum but not disproportionate septal hypertrophy. The mean septal: left ventricular free-wall ratio for the group (n = 10) was 1.37. No correlation was apparent between the occurrence of disproportionate septal hypertrophy and newborn glucose, bilirubin, or hematocrit values. When analyzed separately, the 4 patients who did not receive intrauterine blood transfusions had a ratio of 1.73 +/- 0.21 (mean +/- SEM); this was significantly greater than the ratio in the 6 patients who were transfused in utero (1.13 +/- 0.24). In patients who underwent transfusions, there was no correlation between the number of transfusions and the septal:left ventricular ratio. This study reports a significant but previously unrecognized cardiac hypertrophy with disproportionate septal hypertrophy in patients with erythroblastosis fetalis. Our data suggest a sparing effect of intrauterine fetal transfusions. The mechanism by which these transfusions may affect the hypertrophic development of the myocardium remains to be determined. PMID- 2239862 TI - Lead poisoning and thalassemia trait or iron deficiency. The value of the red blood cell distribution width. AB - The cause of microcytosis and anemia in lead poisoning was investigated using red blood cell distribution width as a screening parameter in 21 consecutive patients with lead poisoning and seven nonrandomly selected patients with iron deficiency and lead poisoning. Of the 21 consecutive patients, 11 had microcytosis as defined by a mean corpuscular volume of less than 72 fL, nine had thalassemia trait (alpha or beta), one had both alpha thalassemia trait and iron deficiency, and one had iron deficiency. The red blood cell distribution width was less than 17.0 in those with thalassemia trait and greater than 17.0 in the iron-deficient subjects. Results of our study suggest that microcytosis in children with lead poisoning is due to coexistent iron deficiency or thalassemia trait. The red blood cell distribution width may be of value in the rapid assessment of the cause of microcytosis in children with lead poisoning. PMID- 2239863 TI - Pediatrician's knowledge and practices regarding parental use of alcohol. AB - Problems with alcohol are common in the United States but are too frequently ignored by physicians, particularly those working with children. We explored pediatricians' knowledge and practices regarding parental use of alcohol and compared these attributes with those of family practitioners. Child health care providers attending three continuing medical education courses in general pediatrics were surveyed using a closed-item questionnaire. One hundred ninety (69%) of the participants responded, including 90 pediatricians and 39 family practitioners. Forty-six percent of responding pediatricians, compared with 90% of family practitioners, stated that they ask about problems with alcohol in taking a routine family history. Thirty-eight percent of pediatricians who knew the frequency of alcoholism, compared with 47% of those who did not, indicated that they include it in taking a routine family history. Forty-six percent of pediatricians who have experienced a problem with alcohol in their own family, compared with 20% of pediatricians without such personal experience, routinely address the issue of alcohol use with parents and children. Similar analyses among the family practitioners revealed no significant differences. We conclude that fewer than half of pediatricians ask about problems with alcohol in taking a family history. The likelihood of asking about such problems was not influenced by the health care provider's knowledge of alcoholism, but it was influenced by the provider's personal family history of problems with alcohol. Because of the important morbidity associated with alcohol use in families, and because intervention can improve functioning and adaptation of the child, training and Continuing Medical Education courses should address this issue. PMID- 2239864 TI - Home care for ventilator-dependent children. Psychosocial impact on the family. AB - The impact of providing home care for ventilator-dependent children was studied in a cross-sectional survey of 18 northern California families. Through the use of a confidential structured interview and the impact on Family Scale, we obtained information on family demographics; the childrens' medical conditions; financial, social, and personal impact on the family; and parental coping-mastery of the care of a ventilator-dependent child at home. Analysis of scores from the impact on Family Scale showed no differences in the perceived family impact between primary caretakers and their spouses. Primary caretakers in the sample, however, showed significantly reduced Coping subscale scores with a longer duration of home ventilatory care. This finding, if confirmed in future studies, has policy implications for physicians and other health professionals working with ventilator-dependent children and their families, especially those who care for children over long periods. PMID- 2239865 TI - Neurodevelopmental performance of very-low-birth-weight infants with mild periventricular, intraventricular hemorrhage. Outcome at 5 to 6 years of age. AB - The neurodevelopmental outcome of 38 very-low-birth-weight neonates (birth weight, less than 1501 g) was followed up prospectively from birth to 5 to 6 years of age to assess the neurodevelopmental sequelae of mild periventricular, intraventricular hemorrhage (grades I and II). All neonates were screened for periventricular, intraventricular hemorrhage at 5 to 10 days of age. Eleven incurred a mild periventricular, intraventricular hemorrhage (group 1) and 27 had no periventricular, intraventricular hemorrhage (group 2). Each of the infants was neurodevelopmentally normal at 1 to 2 years of age. The 38 children were matched by race, age, sex, and socioeconomic status with control children (group 3) who had been born at term. On outcome measurements at 5 to 6 years of age, groups 1 and 2 scored significantly lower than group 3 on the combined test measurements and on three of the four individual measurements. Group 1 scored significantly lower than group 2 on the combined test measurements only. These data indicate that very-low-birth-weight infants are at risk for learning problems. Although children with mild periventricular, intraventricular hemorrhage did not demonstrate a significant deficit on individual test scores, the significant difference on the combined battery suggests that mild periventricular, intraventricular hemorrhage has an adverse effect on global performance. PMID- 2239866 TI - Percutaneous central venous catheterization. Three years' experience in a neonatal intensive care unit. AB - Prolonged venous access is desirable in very-low-birth-weight infants and infants for whom feedings are contraindicated. We prospectively evaluated 481 small diameter venous catheters placed percutaneously in 317 patients over 3 years. Of 478 catheters, 241 (50%) were placed in infants weighing 1 kg or less. Mean catheter stay was 13 days (range, less than 1 to 77 days). Almost half (49%) of the central and thoracic catheters (91% of placements) were removed nonelectively: 43% due to problems such as leaking or clotting and 6% to suspicion of sepsis or venous occlusion. Of the 23 episodes of possible sepsis in the 478 catheter stays, six (1.3%) were confirmed catheter-related sepsis; 12 (2.5%) were confirmed alternate locus sepsis. Three factors specific to percutaneous central venous catheter-related sepsis were prolonged catheter stay (3 to 5 weeks), Staphylococcus epidermidis, and weight less than or equal to 1 kg. Four factors specific to alternate locus sepsis were presence of an alternate infection site, earlier infection (1 to 2 weeks), extremely low birth weight, and prolonged clinical instability. Percutaneous central venous catheterizations reduced the need for the stress of repeated venipuncture, resulting in lower complication rates than those reported with surgically placed central venous catheters, and leading to identification of risk factors specific to catheter sepsis and alternate locus sepsis. PMID- 2239867 TI - Physical features of Prader-Willi syndrome in neonates. AB - A retrospective study of 16 patients was undertaken to identify physical features that may typify neonates with Prader-Willi syndrome. Several features known to be typical of Prader-Willi syndrome in early infancy were confirmed, including hypotonia and genital hypoplasia. A number of features that have not previously been emphasized as characterizing Prader-Willi syndrome were also identified, most notably abnormal cry and, in males, signs of genital hypoplasia but with an apparently normal phallus. Other features included disproportionately large head circumference, disproportionately large anterior fontanelle, mild micrognathia, mild anomalies of the gingivae or alveolar ridges, and changes in the appearance of the skin. Appreciation of these features may assist the pediatrician in recognizing the child with Prader-Willi syndrome during the neonatal period, before the appearance of better-known findings of later onset, such as obesity and acromicria. PMID- 2239868 TI - Cardiovascular responses to exercise in childhood. PMID- 2239869 TI - Risk factors for adolescent cigarette smoking. The Muscatine study. AB - Smoking among adolescents is a developmental phenomenon with several factors exerting an influence on cigarette use at different times. We examined the longitudinal influences of several behavioral and social variables on the smoking status of 443 students followed from early to late adolescence. Of the factors examined, association with friends who smoke and previous smoking status were consistently associated with an adolescent's future smoking status. Other factors, such as attachment to father or to mother, parental supervision, extracurricular activity, perceived negative and positive effects of smoking, and academic involvement, were all related to late adolescent smoking status. These observations suggest that strategies that influence smoking behavior need to be directed not only to the individual child but also to influences within the child's home and school environment. PMID- 2239870 TI - Radiological case of the month. Neonatal small left colon syndrome. PMID- 2239871 TI - Computerized tomography in acute gastrointestinal disorders. AB - In recent years, computerized tomography (CT) has become one of the most important imaging modalities in evaluation of patients with acute gastrointestinal disorders. Its role, diagnostic accuracy, indications, and limitations in some of the most commonly encountered acute abdominal conditions are succinctly presented and reviewed. CT should not be used indiscriminantly, but is best considered a valuable primary or complimentary diagnostic tool in critically ill patients. Its selective use in a variety of emergency abdominal diseases will significantly improve accuracy of clinical diagnoses, leading to a prompt and adequate medical or surgical management. PMID- 2239872 TI - Clinical aspects of Wilson's disease. PMID- 2239873 TI - Effect of omeprazole and high doses of ranitidine on gastric acidity and gastroesophageal reflux in patients with moderate-severe esophagitis. AB - Thirty to fifty percent of patients with reflux esophagitis fail to heal after treatment with conventional doses of H2-receptor antagonists, whereas omeprazole administration induces more than 90% healing. To investigate the effect of omeprazole and higher-than-presently-recommended doses of H2-blockers, we evaluated gastric acidity and gastroesophageal reflux in 17 patients with severe moderate esophagitis before and after treatment with 300 mg ranitidine twice daily or 20 mg omeprazole once daily. Three pH-metric studies were performed, in a cross-over design, before and after 8 days of treatment with omeprazole or ranitidine. Both drugs significantly reduced intragastric acidity (p less than 0.001) during both night and day hours. Median hourly 24-h intragastric pH was 1.8 in the basal study, 2.9 after ranitidine, and 3.4 after omeprazole. Intragastric acidity fell from 84.0 mmol/L in the basal study to 14.2 mmol/L (79% inhibition) with ranitidine and 9.3 mmol/L (84% inhibition) with omeprazole. Patients with esophagitis were significantly more exposed to acid than healthy subjects, in both the supine and upright position (p less than 0.01). The time with esophageal pH less than 4 dropped from 23.9% in the basal study to 8.5% with ranitidine and to 7.2% with omeprazole (p less than 0.001). Both drugs significantly reduced esophageal exposure to acid in both the supine and upright positions (p less than 0.001), whereas neither had any effect on esophageal acid clearance. PMID- 2239875 TI - Dysphagia following fundoplication: "slipped" fundoplication versus achalasia complicated by fundoplication. AB - Failure to obtain preoperative esophageal manometry in patients being considered for antireflux surgery can result in immediate persistent postoperative dysphagia due to a missed diagnosis of achalasia. We describe the clinical assessment and management of a case of delayed postoperative dysphagia due to a "slipped" fundoplication, which is contrasted with three patients with immediate postoperative dysphagia due to a missed diagnosis of achalasia. Surgical revision was required to correct the "slipped" fundoplication, and pneumatic dilatation was successfully used in two of three cases of achalasia complicated by fundoplication. Careful preoperative esophageal evaluation with manometry is essential to rule out the presence of a primary esophageal motor disorder. PMID- 2239874 TI - Esophageal 24-h pH monitoring: is prior manometry necessary for correct positioning of the electrode? AB - In 24-h esophageal pH monitoring, the electrode is usually positioned 5 cm above the manometrically localized esophagogastric junction. In order to replace esophageal manometry for this purpose, we tested whether the esophagogastric junction can be identified correctly by fluoroscopy or the determination of the pH-step between stomach and esophagus, compared with esophageal manometry. The distance from the nares to the esophagogastric junction was determined three times with each of the three methods in 46 patients and 14 volunteers. Fluoroscopy assumed the esophagogastric junction 1.23 +/- 0.23 cm (mean +/- SE) lower than the peak pressure point determined at manometry, pH-step only 0.45 +/- 0.16 cm. With pH-step, only one subject had a difference of more than 3 cm to the manometrically defined esophagogastric junction, whether gastroesophageal reflux disease (as proven by pH monitoring) was present or not. We conclude that the esophagogastric junction can usually be identified with sufficient accuracy by the measurement of the pH-step between stomach and esophagus. Fluoroscopy is far less accurate than pH-step, and should not be used. PMID- 2239876 TI - Endoscopic management of chronic organoaxial volvulus of the stomach. AB - Endoscopic correction of the chronic organoaxial volvulus of the stomach was attempted in seven cases of primary and three cases of secondary volvulus. Endoscopic correction was successful in six cases of primary volvulus and one case of volvulus secondary to duodenal carcinoma. This paper describes the details of the technique of endoscopic correction of gastric volvulus, and documentation of correction of the volvulus by barium meal study with a follow-up of 5-26 months. PMID- 2239877 TI - Recurrence of duodenal ulcer and elevated serum pepsinogen I levels in smokers and nonsmokers. AB - We determined serum pepsinogen I (PG I) levels by radioimmunoassay in 472 patients with duodenal ulcer and 141 normal subjects to investigate whether serum PG I levels were related to cigarette smoking, and in 225 patients to determine whether the recurrence of duodenal ulcer was related to serum PG I levels or cigarette smoking. Serum PG I levels were not influenced by cigarette smoking in either patients with duodenal ulcer or normal subjects. The recurrence rate of duodenal ulcer not under maintenance therapy was significantly higher in hyperPG I patients than in normoPG I patients, regardless of their smoking habits. Only in hyperPG I patients was the recurrence rate in smokers higher than in nonsmokers. Patients under maintenance therapy showed similar results. Multilogistic regression indicated that hyperPG I had a greater effect than cigarette smoking on ulcer recurrence. These findings indicate that serum PG I levels are not influenced by smoking, and the important characteristic in patients with recurrent duodenal ulcers is the increased serum PG I levels. PMID- 2239879 TI - Granular cell tumor of the esophagus: endoscopic ultrasonographic demonstration and endoscopic removal. AB - A 35-yr-old Japanese man with a granular cell tumor of the esophagus that was removed by endoscopic polypectomy is presented. Radiography and endoscopy showed a 20 x 12 mm sessile protrusion in the distal esophagus. Endoscopic ultrasonography demonstrated the hypoechoic mass in the submucosa without continuity to the muscularis propria. The lesion was successfully treated by endoscopic polypectomy without complications. The cross-sections of the resected specimen were quite in agreement with the ultrasonographic findings. Endoscopic ultrasonography is valuable to assess the exact location and extent of the tumor, and to determine the indication for endoscopic polypectomy. PMID- 2239878 TI - Adenocarcinoma arising in Barrett's esophagus after total gastrectomy. AB - A 64-yr-old Japanese male who underwent a partial gastrectomy for a duodenal ulcer at the age of 21, a total resection of the remnant stomach for a stomal ulcer at age 25, and in whom Barrett's esophagus was diagnosed at age 47, was found to have a tumor at the distal esophagus and was operated on by thoracic esophagectomy. The tumor was a well to moderately differentiated adenocarcinoma invading down to the muscularis propria. The entire esophageal mucosa in the resected specimen was lined by columnar epithelium. This tumor was thought to derive from the Barrett's esophageal epithelium. PMID- 2239880 TI - Extramedullary hematopoiesis involving the esophagus in myelofibrosis. AB - In this report, we describe a case of myelofibrosis with myeloid metaplasia; a 53 yr-old man was splenectomized for a massively enlarged spleen in which multiple foci of myeloid metaplasia were histologically demonstrated. The patient was referred to us for endoscopic examination, following the repeated occurrence of melena. Upper gastrointestinal endoscopy revealed two active ulcerative lesions in the bulb, and only a moderate erythema in the lower third of the esophagus, which showed no varices. There was no endoscopic evidence of active or recent bleeding. Subsequent histologic examination of biopsies taken from the esophageal lesion surprisingly revealed the presence of hematopoietic tissue. PMID- 2239881 TI - Diffuse hemangiomatosis of the spleen: splenic hemangiomatosis presenting with giant splenomegaly, anemia, and thrombocytopenia. AB - In an elderly patient with oligosymptomatic giant splenomegaly, clinical and laboratory data were nondiagnostic, while nonhomogeneous splenic enlargement was the only finding detected by imaging procedures. Splenectomy was performed and diffuse hemangiomatosis of predominantly capillary-type found. The failure of imaging techniques to even hint at the nature of the underlying disorder is comprehensible in view of the organ being essentially replaced in toto by the abnormal vascular channels. Diffuse splenic hemangiomatosis, a rare condition, may cause hypersplenism, and its diagnosis may be elusive because of misleading patterns on imaging. PMID- 2239882 TI - "Spontaneous sump syndrome": Successful treatment by duodenoscopic sphincterotomy. AB - "Sump syndrome" is a rare complication of side-to-side choledochoenterostomy operations which develops in the distal, nonfunctioning limb of the common bile duct where lithogenic bile, gastrointestinal contents, and debris accumulate. We report here a patient who developed spontaneous sump syndrome as a result of the formation of choledochoduodenal fistula, and who presented with multiple pyogenic liver abscesses. The patient's symptoms and liver abscesses resolved completely after treatment by endoscopic sphincterotomy and antibiotics. This case demonstrates that sump syndrome may occur spontaneously, that it can be a cause for pyogenic liver abscess formation, and that it may be treated effectively by endoscopic sphincterotomy. PMID- 2239883 TI - Hepatic portal venous gas: an unusual presentation of Crohn's disease. AB - Hepatic portal venous gas is associated with numerous conditions and traditionally has been regarded as an ominous prognostic sign. There are several reports of hepatic portal venous gas occurring in patients with inflammatory bowel disease after or during the performance of colonic diagnostic studies. We report an unusual case of Crohn's disease whose initial presentation included hepatic portal venous gas. The literature of hepatic portal venous gas associated with inflammatory bowel disease is reviewed. PMID- 2239884 TI - Primary abscess of the omentum. AB - A 65-yr-old man presented with upper abdominal pain and fever due to a primary abscess of the omentum. The finding of microscopic-size foreign particles within the abscess raised the possibility of antecedent clinically silent perforation of the bowel or appendix. Surgical resection and antibiotic therapy were curative. PMID- 2239885 TI - A chance to cut is a chance to cure? AB - Fifty-seven patients underwent local excision of an invasive distal rectal cancer as an initial operative procedure with curative intent. Five-year survival was 82.5%, and the rectal cancer specific mortality rate was only 10.5%. The level of wall invasion, vascular permeation, tumor ulceration, mobility, and differentiation were the criteria studied for prognosis. Poor prognostic factors included mucinous cell differentiation and full thickness invasion, and in these cases, abdominoperineal resection was recommended. None of the 27 patients without these adverse prognostic factors died from rectal cancer. The other factors did not appear to influence the outcome, and local excision of distal rectal cancer would be the treatment of choice in such selected patients. PMID- 2239886 TI - Oral dissolution therapy for cholelithiasis: mix and match. AB - The authors conducted a prospective, randomized trial of chenodeoxycholic and ursodeoxycholic acid versus ursodeoxycholic acid alone in patients with cholelithiasis to determine their efficacy for dissolution of gallstones. One hundred and twenty patients with radiolucent gallstones, less than or equal to 15 mm and who had a functioning gallbladder were enrolled. The patients were divided into two groups based on the diameter of their largest stones. Seventy patients had stones larger than 5 mm but less than 15 mm, whereas 50 patients had stones that measured 5 mm or less. The patients were randomly assigned to treatment with chenodeoxycholic acid plus ursodeoxycholic acid (5 mm/kg of each) or ursodeoxycholic acid (10 mm/kg) alone. Oral cholecystography, plain abdominal x rays, and ultrasonography of the gallbladder were done at 6, 12, and 24 months. Dissolution was deemed to be complete if not stones were visualized on two examinations. partial dissolution was defined as a 50% reduction in stone size and/or number. Stones that were not detected by cholecystography but still detected during ultrasonography were considered to be partially dissolved. Plasma triglycerides, serum cholesterol, HDL, and serologic liver function tests were determined at 1, 3, 6, 12, 18, and 24 months. In a select group of patients, bile rich duodenal aspirates were aspirated and analyzed for biliary lipid contents. In the group with small stones, defined as less than or equal to 5 mm, complete stone dissolution occurred significantly more often utilizing combination therapy at 6 months (52% vs 24%), and this trend persisted, although no longer significant, at 12 and 24 months. Combination therapy also achieved an improved rate of dissolution for large stones within 6 months; however, this did not persist at 12 and 24 months. Although not statistically significant, stone calcification occurred less often with combined therapy. All treatment regimens were well tolerated, with only minor changes in bowel habits and mild elevations in serum transaminase levels. Serum lipid levels did not change with either therapy. The authors concluded that the combination of chenodeoxycholic acid and ursodeoxycholic acid was the preferred therapy for gallstone dissolution, because it dissolves stones more rapidly, with a lower incidence of stone calcifications, and thus might reduce the long-term cost of treatment. PMID- 2239887 TI - "Cloggology" revisited: endoscopic or surgical decompression of malignant biliary obstruction. AB - In this study, 50 consecutive patients over age 60 with obstructive jaundice secondary to malignant stricture of the distal common bile duct were identified by endoscopic cholangiography. The patients were then randomized to palliative therapy with either endoscopic endoprosthesis or bypass surgery. Prospective indices of survival time, complication rates, hospitalization requirements, and quality of life were followed. All 25 patients randomized to endoprosthesis were treated by this procedure, whereas only 19 of 25 patients randomized to bypass surgery underwent operative biliary-digestive anastomosis. No difference in the above indices were found between the two groups. The authors concluded that palliation of obstructive jaundice due to a malignant bile duct stricture with endoscopically placed biliary stent is as effective as operative bypass. PMID- 2239888 TI - Very prolonged diarrhea associated with Aeromonas hydrophila. PMID- 2239889 TI - Gastric bezoar complicating gastric stapling. PMID- 2239890 TI - Pathogenesis of chronic alcoholic pancreatitis. PMID- 2239891 TI - High doses of 5-aminosalicylic acid enemas in chronic radiation proctitis: comparison with betamethasone enemas. PMID- 2239892 TI - The microcirculatory status of portal hypertensive gastric mucosa in "normal" and postsclerotherapy patients. PMID- 2239893 TI - Pancreatic and biliary obstruction due to eosinophilic gastroenteritis. PMID- 2239894 TI - Re: "Time trends in incidence rates of first hip fracture in the Uppsala Health Care Region, Sweden, 1965-1983". PMID- 2239895 TI - Re: "Prognosis after breast cancer diagnosis in women exposed to estrogen and estrogen-progestogen replacement therapy". PMID- 2239896 TI - Re: "Case-control studies using other diseases as controls: problems of excluding exposure-related diseases". PMID- 2239897 TI - Hyperinsulinemia and elevated blood pressure: cause, confounder, or coincidence? PMID- 2239898 TI - Racial/ethnic differences in HIV-1 seroprevalence and risky behaviors among intravenous drug users in a multisite study. AB - Differences in human immunodeficiency virus type 1 (HIV-1) seroprevalence and patterns of drug-use and sexual behaviors were examined among Hispanic, black, and white intravenous drug users recruited at multiple sites in Worcester, Massachusetts. A total of 1,092 (786 males, 306 females) intravenous drug users were interviewed, and HIV-1 antibody test results were available for 874 (80.0%). After adjustment for demographic differences, black males were significantly less likely to report risky drug-use behaviors (ever sharing needles and recently visiting shooting galleries) compared with white males. In contrast, Hispanic males were significantly more likely to report recent risky drug-use behaviors (sharing needles in New York City, daily needle-sharing, and visiting shooting galleries). Both groups were less likely to report risky sexual behaviors compared with whites. The odds ratios for HIV-1 seropositivity remained significantly greater than 1 for Hispanics compared with whites (odds ratio = 4.5) and maintained marginal significance for blacks compared with whites (odds ratio = 2.1) when adjusted for risky behaviors and demographic variables. The different patterns of drug-use and sexual behaviors by race/ethnicity indicate the need for interventions targeted to specific populations. PMID- 2239899 TI - Association of drug injection patterns with antibody to human immunodeficiency virus type 1 among intravenous drug users in Baltimore, Maryland. AB - During 1988 and 1989, intravenous drug users recruited through extensive community outreach efforts in Baltimore, Maryland, were interviewed about drug injection and sex practices in the prior 11 years, with screening for antibody to human immunodeficiency virus type 1 (HIV-1). Neither interviewers nor subjects were aware of HIV-1 serostatus until 2 weeks after the interview. Among 2,616 intravenous drug users who last injected drug within the same calendar year as screening, HIV-1 seroprevalence was 30.1% for those with any use of shooting galleries, 23.3% for those who shared needles but did not use shooting galleries, and 16.3% for drug users who denied both needle-sharing and gallery use between 1977 and 1987. Among 608 drug users who reported persistent use of shooting galleries since 1977 or subsequent initiation into drug use, there was a tendency for HIV-1 seroprevalence to increase with more recent onset of an injection career. Combined with a milder but similar tendency among 739 drug users who reported persistent sharing of needles, and a seroprevalence of 15.1% among participants who had just started injecting drugs in the 18 months prior to baseline, these data provide indirect evidence that a high risk for HIV-1 infection might occur early during a drug injection career. PMID- 2239900 TI - Serum vitamin A and subsequent risk of cancer: cancer incidence follow-up of the Finnish Mobile Clinic Health Examination Survey. AB - From 1968 to 1977, the association between the level of vitamin A in serum and the subsequent incidence of cancer was examined in a longitudinal study of 36,265 persons initially aged 15-99 years in 25 population groups in Finland. During a mean follow-up of 8 years, 766 cancers were diagnosed. Serum retinol, retinol binding protein, and beta-carotene levels were measured from frozen serum samples (stored at -20 degrees C) drawn from these persons before the start of follow-up and from 1,419 controls matched for sex, age, and place of residence who did not develop cancer during follow-up. The mean level of serum retinol among the cancer cases was 645 micrograms/liter for men and 587 micrograms/liter for women. The corresponding levels in the controls were 3.3% and 2.8% higher. There was an inverse gradient between serum retinol level and the occurrence of cancer among men. This association was, however, mainly concentrated in the first 2 years of follow-up. The mean level of serum beta-carotene was 72.3 micrograms/liter among male cases and 119.5 micrograms/liter among female cases. The corresponding levels of the controls were 14.0% and 5.5% higher. The differences were particularly clear with regard to lung cancer. These findings suggest that the association between retinol and cancer may be due to preclinical cancer and that there may be an association between beta-carotene and cancer. PMID- 2239901 TI - A case-control study of milk-drinking and ovarian cancer risk. AB - It has been hypothesized that milk consumption increases the risk of ovarian cancer because of a possible association of lactose with human ovarian failure. Milk is also a source of animal fats in the diet, and animal fat intake is associated with ovarian cancer risk. To explore further the possible confounding of the milk-ovarian cancer association by the animal fat content of milk, the authors performed a case-control study of 303 ovarian cancer cases and 606 age matched nonmalignant-disease controls seen between 1982 and 1988 at Roswell Park Memorial Institute in Buffalo, New York. Total frequency of usual milk intake was not associated with increased risk. Usually drinking more than one glass of whole milk daily relative to never drinking whole milk was associated with a relative risk of 3.1 (95% confidence interval (CI) 1.8-5.5). Consumption of reduced-fat milk was associated with reduced relative risk. Among persons who reported drinking milk regularly, persons reporting drinking only whole milk were at increased risk (relative risk = 2.6, 95% CI 1.7-4.0) relative to persons who drank only skim milk or 2% milk. These findings suggest that milk-drinking is not a source of ovarian cancer risk independently of its fat content. Additional study of lactose and ovarian cancer risk involving careful control for confounding is needed. PMID- 2239902 TI - Hip fractures in women with breast cancer. AB - The authors investigated whether the incidence of first hip fracture, an indicator of osteoporosis, is lower in breast cancer patients, who are assumed to have higher levels of endogenous estrogens, than in other women. A population based Swedish cohort comprising 9,673 women with invasive breast cancer diagnosed from 1958 through 1983 was followed up with respect to the occurrence of a first hip fracture during the period 1965-1983. Overall, the number of observed acute fractures (n = 387) was slightly higher than expected (n = 348.6) (standardized incidence ratio (SIR) = 1.1, 95% confidence interval (CI) 1.0-1.2). Risk for trochanteric fractures was slightly higher than expected (SIR = 1.2, 95% CI 1.0 1.4), but risk for cervical fractures was not (SIR = 1.0, 95% CI 0.9-1.1). Risk for trochanteric fracture decreased with increasing age at breast cancer diagnosis, reaching standardized incidence ratios close to unity after the age of 70 years. Duration of follow-up appeared to be unrelated to the risk of either type of fracture. The authors conclude that the incidence of first hip fracture is not lower in breast cancer patients than in other women. PMID- 2239903 TI - The relation of endogenous sex steroid hormone concentrations to serum lipid and lipoprotein levels in postmenopausal women. AB - The relation of concentrations of endogenous estrogens and androgens to lipid and lipoprotein levels was examined in 176 white, postmenopausal women (mean age, 58 years) with an average of 9 years since the onset of menopause. All of the women were participants in a clinical trial of the effect of walking on postmenopausal bone loss. In that trial, women were randomized into either a walking group or a control group and were followed for 3 years. There were no differences in the serum hormones or lipids by randomized group, and hence, results from this study are presented for both groups combined. None of the women were on estrogen replacement therapy. Data were available from year 1 (1982-1983) of the trial for the estrogens, lipids, and lipoproteins. Information on androgens was available for 143 of these women. Hormone levels were determined by highly specific methods involving extraction, column chromatography, and radioimmunoassay. About 50% of the women had estradiol levels at or below the sensitivity level (2.5 pg/ml) of the assay; therefore, estradiol levels were viewed as dichotomous (measurable/not measurable), and the estradiol results should be interpreted with caution. There was little relation of the androgens to the lipid values. Univariate analyses suggested a direct relation between total cholesterol, low density lipoprotein cholesterol, and triglyceride levels with estradiol. An inverse relation was suggested between serum estrone and estradiol and total high density lipoprotein (HDL) cholesterol and HDL2 cholesterol, although none of these associations were statistically significant. Multiple regression analyses revealed that the primary determinant of the HDL cholesterol and triglyceride levels was the degree of obesity as estimated by the body mass index (weight (kg)/height (m)2). Addition of estrone or estradiol to the models did not contribute to the prediction of lipid levels. These results do not support the hypothesis of there being a relation between endogenous sex hormone levels and lipid levels in postmenopausal women. The results suggest that sex hormones cannot explain the sex difference in lipid levels and may not contribute to the rise in coronary heart disease that occurs in women around menopause. PMID- 2239904 TI - Endogenous sex hormone levels in older adult men with diabetes mellitus. AB - In a Southern California population-based cohort of 985 men aged 40-79 years in 1972-1974, 110 men with diabetes had significantly lower mean levels of endogenous plasma testosterone and sex hormone-binding globulin than did 875 nondiabetic men. Mean androstenedione, estrone, and estradiol levels did not differ significantly by diabetic status. The testosterone and sex hormone-binding globulin differences were reduced but not eliminated after adjustment for age and body mass index (weight (kg)/height (m)2). Twenty-one percent of diabetic men compared with 13% of nondiabetic men had testosterone levels below a categorically defined normal level of 3,500 pg/ml. Testosterone was inversely related to degree of glycemia in the whole cohort. Throughout the whole range of plasma glucose, there was a stepwise decrease in mean testosterone levels per categorical increase in fasting plasma glucose, apparent in both diabetics and nondiabetics. The clinical and physiologic implications of the reduced testosterone levels in diabetic men merit further investigation. PMID- 2239905 TI - A prospective population-based study of alcohol use and non-insulin-dependent diabetes mellitus. AB - The effect of alcohol use on risk of non-insulin-dependent diabetes mellitus was assessed in a defined population. A 24-hour recall of alcohol intake and past week alcohol intake were obtained by separate interviewers between 1973 and 1975, and responses were coded by the Nutrition Coordinating Center, University of Minnesota. Of the 524 adults aged 30-79 years without diabetes at baseline, 31 men and 44 women were identified as diabetic by means of a glucose tolerance test (World Health Organization criteria) between 1984 and 1987. Men, but not women, who developed diabetes reported significantly more alcohol intake in the past week and in the past 24 hours. The highest rate of diabetes among alcohol users was in heavy drinkers--statistically significant only in men. Alcohol use remained a significant predictor of diabetes in men after adjustment for baseline age, body mass index (weight (kg)/height (m)2), cigarette smoking, family history of diabetes, and systolic blood pressure with a logistic regression model. The relative risk associated with past-week alcohol intake was 1.5 per 137.8 g; for past-24-hour alcohol intake, it was 1.5 per 24.5 g. Adjustment for baseline fasting plasma glucose and triglycerides did not change the results. Alcohol intake appears to be associated with risk of non-insulin-dependent diabetes mellitus in men. PMID- 2239906 TI - The epidemiology of appendicitis and appendectomy in the United States. AB - To describe the epidemiology of appendicitis and appendectomy in the United States, the authors analyzed National Hospital Discharge Survey data for the years 1979-1984. Approximately 250,000 cases of appendicitis occurred annually in the United States during this period, accounting for an estimated 1 million hospital days per year. The highest incidence of primary positive appendectomy (appendicitis) was found in persons aged 10-19 years (23.3 per 10,000 population per year); males had higher rates of appendicitis than females for all age groups (overall rate ratio, 1.4:1). Racial, geographic, and seasonal differences were also noted. Appendicitis rates were 1.5 times higher for whites than for nonwhites, highest (15.4 per 10,000 population per year) in the west north central region, and 11.3% higher in the summer than in the winter months. The highest rate of incidental appendectomy was found in women aged 35-44 years (43.8 per 10,000 population per year), 12.1 times higher than the rate for men of the same age. Between 1970 and 1984, the incidence of appendicitis decreased by 14.6%; reasons for this decline are unknown. A life table model suggests that the lifetime risk of appendicitis is 8.6% for males and 6.7% for females; the lifetime risk of appendectomy is 12.0% for males and 23.1% for females. Overall, an estimated 36 incidental procedures are performed to prevent one case of appendicitis; for the elderly, the preventive value of an incidental procedure is considerably lower. PMID- 2239907 TI - Maternal cigarette smoking during pregnancy in relation to oral clefts. AB - Studies on maternal smoking in relation to oral cleft defects have yielded inconsistent findings, with results ranging from no association to sixfold increases in risk. The authors examined this relation in a case-control study conducted in Boston, Massachusetts, Philadelphia, Pennsylvania, Toronto, Ontario, Canada, and the state of Iowa during the years 1983-1987, in which mothers of malformed infants were interviewed within 6 months after delivery about prenatal events and exposures. Maternal cigarette smoking during pregnancy for 400 infants with cleft lip with or without cleft palate and for 215 infants with cleft palate alone was compared with that for 2,710 infants with other malformations (controls). Relative risks (and 95% confidence intervals) were estimated for smokers of 1-14, 15-24, and greater than or equal to 25 cigarettes per day relative to never smokers; the respective estimates for cleft lip with or without cleft palate were 1.2 (95% confidence interval (CI) 0.9-1.6), 1.4 (95% CI 1.0 2.1), and 0.7 (95% CI 0.3-1.6), and for cleft palate alone, estimates were 1.0 (95% CI 0.7-1.5), 0.9 (95% CI 0.5-1.5), and 0.8 (95% CI 0.3-2.2). Relative risks were also close to unity for case subgroups divided according to the presence or absence of an associated malformation. Multivariate control of several potential confounders did not alter these estimates. Based on this large series of cases, maternal smoking during pregnancy does not appear to increase the risk of oral clefts. PMID- 2239908 TI - Maternal employment and reproductive risk factors. AB - Studies of reproductive hazards in the workplace must address potential biases related to selection for employment. The National Natality Survey, a probability sample of live births to married women in 1980, was used to examine the relation between female employment during pregnancy and factors that might affect reproductive outcome by analyzing the 5,927 women with complete occupational data. Demographic and behavioral attributes as well as reproductive history were compared for the 3,712 women employed and the 2,215 women not employed during pregnancy. Employed mothers were of more optimal reproductive age, were more highly educated, had higher incomes, began prenatal care earlier, had greater weight gain during pregnancy, and were slightly less likely to be heavy smokers. Employed women had markedly fewer previous births and less favorable reproductive histories (more stillbirths, miscarriages, and induced abortions) than unemployed women, controlling for gravidity. Full- and part-time workers were similar with regard to demographic and behavioral characteristics, but part-time workers had higher parity. Differences were noted by employment sector: professional women had especially favorable demographic and behavioral traits, and women employed as operatives and service workers were less advantaged. These results indicate that substantial differences in pregnancy-related risk factors exist in relation to employment, with working women generally having more favorable demographic and behavioral characteristics and less favorable reproductive histories. This pattern could produce selection bias in studies of work and reproductive health, and it encourages the restriction of comparison groups to other employed women, with a need to consider heterogeneity among working women as well. PMID- 2239909 TI - The prevalence of Chlamydia trachomatis infection among mothers of children with trachoma. AB - The authors studied the epidemiology of Chlamydia trachomatis infection in a trachoma-endemic area of central Kenya. Children with abnormal ocular discharge were evaluated for clinical evidence of trachoma and were cultured for C. trachomatis. Isolated strains of C. trachomatis were immunotyped with monoclonal antibodies. Overall, 221 children from 207 families were evaluated. Clinically, 91 children (41%) had trachomatous follicular inflammation, and 130 (59%) had papillary hypertrophy without visible follicle and were labeled as having mucopurulent conjunctivitis. C. trachomatis was isolated from 31 of 91 children with trachoma (34%) and 17 of 130 children with conjunctivitis (13%) (p less than 0.001). Twenty-two C. trachomatis strains were immunotyped: 17 were from children with trachoma (nine type A, one A/L2, five B, one Ba, and one E) and five were from children with conjunctivitis (two A, one Ba, one D, and one F). A total of 168 mothers were evaluated for cervical C. trachomatis infection, and seven (4%) were culture-positive. Two strains were immunotyped as serovar E. The authors conclude that C. trachomatis ocular infections are due to heterogeneous serovars in this area, that most cases of trachoma are due to C. trachomatis infection with the classic trachoma serovars (A, B, or Ba), and that cervical C. trachomatis infection is uncommon among mothers of children with trachoma. PMID- 2239910 TI - A nested case-control study of the correlates of early menarche. AB - Age at menarche, an early determinant of breast cancer risk, shows both a downward secular trend and marked differences by socioeconomic status, both presumably the reflection of dietary variations. A cohort study is being conducted in the Quebec City, Canada, area to assess the relation between diet, physical activities, and menarche. In the fall of 1986, 3,022 fifth-grade girls (mean age, 10.7 years) agreed to participate in the study. All of the girls' parents provided information on health, familial, and socioeconomic variables. A 3-day dietary record and a 7-day physical activity recall were provided by 95.8% of the girls. All dietary information was verified with each girl by a dietician. Body weight and height and two skinfold thickness measurements were also recorded for 98% of the subjects. At the beginning of the study, 107 girls had already experienced menarche. In the fall of 1987, letters were sent to the mothers of the remaining 2,915 girls; 2,854 (97.9%) responded. In the preceding year, 352 girls had reached menarche. Of these, 333 (94.6%) had provided baseline dietary data. A case-control analysis was conducted in which these 333 girls were compared with 333 age-matched premenarcheal girls. There was a weak association between energy intake, energy expenditure, and early menarche. Weight, height, skinfold thickness, mother's age at menarche, and participation in a dance, ballet, gymnastics, or figure skating club were also associated with the early onset of menstruation. PMID- 2239911 TI - Depressed mood and development of cancer. AB - This study was undertaken to determine whether premorbid depressed mood is associated with the development of cancer. Scores on the Center for Epidemiologic Studies Depression Scale were available for 2,264 participants in a mental health study conducted in 1971-1974 in Washington County, Maryland, who were still free of cancer 2-4 years later. Over a 12-year follow-up period (1975-1987), 169 cancers were diagnosed among these persons. While there was only a slight association of depressed mood with subsequent cancer among the total study population, the association was much stronger among cigarette smokers. Compared with the risk seen in never smokers without depressed mood, depressed mood at the highest level of smoking was associated with relative risks of 4.5 for total cancer, 2.9 for cancer at sites not associated with smoking, and 18.5 for cancer at sites associated with smoking. PMID- 2239912 TI - The association between change in cognitive function and longevity in Dutch elderly. AB - The association between rate of change in cognitive function and longevity was investigated with data from the Dutch Longitudinal Study Among the Elderly. A group of 211 Dutch persons aged 65-84 years at baseline (1955-1957) was reexamined twice during an 8-year follow-up period, after which mortality was ascertained through 1983. Cognitive function was assessed based on an adaptation of the Wechsler Memory Scale. Rate of change in cognitive function during the 8 years of follow-up was determined by regression on time for each individual. Cognitive function declined significantly over the 8-year period (mean yearly change, -0.28 units; 95% confidence interval -0.34 to -0.22). The rate of decline in cognitive function was strongly associated with subsequent survival time in the ages 70 years and over, with those with a large decline having a short survival time. No association could be demonstrated in the age group 65-69 years. Adjustment for potential confounders did not affect the magnitude of the association. These findings suggest that the rate of decline of cognitive function is an independent predictor of longevity in older persons. PMID- 2239913 TI - Mortality by employment status in the National Longitudinal Mortality Study. AB - A mortality follow-up of 452, 192 persons aged 25 years or more who were characterized with respect to employment status was conducted using the National Death Index for the years 1979 through 1983. The cohort, part of the National Longitudinal Mortality Study, was drawn from Current Population Survey samples representative of the US population using selected months during the years 1979 1983. Employed persons aged 25-64 years were found to have standardized mortality ratios from 61% to 74% of the average, depending upon their sex and race. Unemployed men had standardized mortality ratios slightly above 100, but these values were 1.6 and 2.2 times higher than those for employed white men and black men, respectively. Those classified as unable to work had very high mortality ratios, from two to seven times the average. In the older age groups, 65 years or more, very low mortality ratios were found for those who were still employed. These relations were maintained after adjustment for family income and educational level. These results 1) describe the magnitude of mortality risk for clearly defined employment categories, 2) identify segments of the population with especially high mortality requiring greater public health recognition, and 3) suggest further research into the health consequences of the various employment/nonemployment conditions. PMID- 2239915 TI - Variability in nutrient and food intakes among older middle-aged men. Implications for design of epidemiologic and validation studies using food recording. AB - The authors conducted a dietary methodology study in 1984 in Finnish men aged 55 69 years in order to validate two dietary assessment instruments being used in the US-Finland Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Trial. Twelve 2-day food records collected from 162 men over a 6-month period, including every day of the week, served as the reference measure. This report focuses on three important questions for investigating diet and disease relations: 1) How many days are necessary to classify "usual" intake? 2) Is there loss as a result of using consecutive days? 3) Which days are necessary for assessment and classification of "usual" diet? A repeated-measures regression model was used to estimate the variance components and the effects of consecutive days, weekday (weekday vs. weekend), and season. Correlations between the averages of different numbers of days of food records and "true" usual intake were examined along with the resulting attenuations in relative risk. Results suggest that 7-14 days are required to adequately classify most individuals into categories of intake for most nutrients and some foods. There appears to be some loss of information from using consecutive days rather than days further apart. Weekday/weekend differences in mean intakes are slight, and the rank ordering of individuals appears to be preserved. A moderate seasonal effect is shown for classification of fruits, but only a slight one is seen for micronutrients and berries. Implications for the design of epidemiologic and validation studies are discussed. PMID- 2239914 TI - Accuracy of death certificate diagnosis of intracranial hemorrhage and nonhemorrhagic stroke. The Minnesota Heart Survey. AB - The validity of death certificate diagnosis of stroke and its type as the underlying cause of death was investigated in a sample of in-hospital deaths of possible stroke cases from the Minnesota Heart Survey. The 228 in-hospital deaths in 1970 and the 180 deaths in 1980 had a stroke diagnosis either on hospital discharge records or as the underlying cause of death on the death certificate. Relative to a standardized physician diagnosis, positive predictive values for the death certificate diagnosis in 1970 were 96% for all types of stroke, 59% for intracranial hemorrhage, and 87% for nonhemorrhagic stroke. The respective values in 1980 were 100%, 82%, and 97%. An increase in positive predictive values, particularly for intracranial hemorrhage between 1970 and 1980, was attributed to the increased use of computerized tomography. Sensitivity for the death certificate diagnosis in 1970 was 63% for all types of stroke, 66% for intracranial hemorrhage, and 45% for nonhemorrhagic stroke. The respective sensitivities in 1980 were 70%, 76%, and 58%. The lower sensitivity for nonhemorrhagic stroke as compared with hemorrhagic stroke was due in part to 1) frequent reporting of nonhemorrhagic stroke as a contributing cause of death rather than the underlying cause of death and 2) time from stroke onset to death. Specificity among these possible strokes was high in both years. The low sensitivity of death certificate diagnosis of stroke may reduce estimated relative risks in epidemiologic studies. Nevertheless, since the advent of widespread use of computerized tomography, a death certificate diagnosis of intracranial hemorrhage versus nonhemorrhagic stroke appears to be sufficiently accurate for use in epidemiologic studies of stroke etiology. PMID- 2239916 TI - The size and number of bone marrow megakaryocytes in malignant lymphoma and their relationship to abnormalities in platelet count. AB - Platelet counts were measured routinely in 718 volunteer blood donors and 124 patients with malignant lymphoma. When considered by gender, the mean platelet counts of the patients with malignant lymphoma were significantly increased when compared to controls (P less than 0.01). In addition, 9% of males and 4% of females with lymphoma exhibited a thrombocytosis, in which their platelet counts exceeded the upper limit of the normal platelet count for control subjects (defined as 2 SDs in excess of the mean value). Megakaryocyte whole size, cytoplasmic and nuclear sizes, and megakaryocyte numbers were also quantified in bone marrow obtained from the iliac crest of 5 hematologically normal subjects and 26 patients with malignant lymphoma. Mean megakaryocyte sizes were significantly greater in subjects with lymphoma, when compared to control values (P less than 0.05). No significant differences in megakaryocyte numbers in bone marrow were observed between the two groups. For subjects with malignant lymphoma, platelet count was found to be significantly positively correlated with megakaryocyte size. The results of this study suggest that the elevated platelet count associated with malignant lymphoma is mediated by an increase in the size of the megakaryocytes in the bone marrow. PMID- 2239917 TI - Major prognostic factors of Japanese patients with lymphoma-type adult T-cell leukemia. AB - Fifty-three Japanese patients with the lymphoma-type adult T-cell leukemia (ATL) were analyzed to study the prognostic value of various clinical findings recorded at the time of diagnosis. All patients were positive for human T-cell leukemia virus type I (HTLV-I) antibody and demonstrated monoclonal integration of HTLV-I proviral DNA in their malignant cells. The important individual variables detected in a previous univariate analysis were placed in a multiple regression model to identify the major prognostic factors for survival. This analysis showed that serum lactate dehydrogenase (LDH), calcium, and total protein levels had a strong predictive relationship with the length of survival (in descending order of importance). Among the 53 patients, 46 were dead at the time of analysis. The cause of death in relation to the duration of survival is also reviewed in this article. PMID- 2239918 TI - Acute myelomonocytic leukemia: an immunoelectron microscopic study. AB - Acute myelomonocytic leukemia (M4; French-American-British classification) is light microscopically defined as the leukemia constituting leukemic cells in both granulocytic and monocytic lineages. Therefore, the characteristics of M4 have not been fully elucidated. The author previously indicated that normal neutrophilic granulocytes could be ultrastructurally differentiated from normal monocytes by the double staining of lactoferrin and lysozyme. In this investigation, the ultrastructural localization of both proteins were observed in order to make the outline of M4 clear. The leukemic cells in acute myeloid leukemia (M2) were also examined in comparison with those in M4. The leukemic cells in M4 showed the double stainability of lactoferrin and lysozyme, and the positive reactions were localized in the cytoplasmic matrix and in the granules. The staining pattern was similar to that in M2. The coexistence of lactoferrin and lysozyme in the leukemic cells in M4, which has ultrastructurally the monocytic characteristics, implied that the leukemic cells also possess the characteristics of the cells in the granulocytic lineage. This suggests that the presence of the various leukemic cells in the granulocytic lineage. This suggests that the presence of the various leukemic cells signifies the diversely abnormal maturations in vivo of the monocytes/granulocytes precursor cell and that M4 consists of not two kinds of distinguishable cells of granulocytic and monocytic lineages but various consecutive cells based on a malignant transformation of the precursor cell. PMID- 2239919 TI - Dry tap bone marrow aspiration: clinical significance. AB - Failure to obtain bone marrow on attempted marrow aspiration, "dry tap," has commonly been ascribed to faulty technique. All reports of simultaneous marrow aspirations and biopsies performed at the University of Virginia between January 1, 1983, and July 1, 1989, were reviewed to determine the frequency of dry taps, the diagnoses and pathologic findings in these cases, and the associated laboratory findings. Among 2,235 simultaneous bone marrow aspirations and biopsies, 87 were dry taps (3.9%). Of these 87 dry taps, only six (6.9%) showed normal marrow biopsies, whereas the majority showed significant marrow pathology, usually associated with fibrosis, or hypercellularity, or both. These conditions most likely account for the inability to aspirate marrow. The most frequent diagnoses were metastatic carcinoma (17.2%), chronic myelogenous leukemia (14.9%), idiopathic myelofibrosis (13.8%), and hairy cell leukemia (10.3%). The presence of peripheral blood nucleated red blood cells, thrombocytopenia, and elevation of the serum lactate dehydrogenase were frequent findings in patients who experienced dry taps. Methods to obtain sufficient marrow for rapid diagnosis in these cases are discussed. PMID- 2239920 TI - Developmental and inducible patterns of human theta 1-globin gene expression in embryonic/fetal and adult erythroid cells. AB - Human theta (theta 1)-globin gene represents a member of the alpha-like globin gene family residing on chromosome 16. theta 1-Specific transcripts have been detected so far only in erythroid tissues and in erythroleukemia K562 cells. To investigate systematically its inducible expression and developmental specificity, we analyzed at the RNA level five additional human erythroleukemia cell lines with diverse developmental globin programs, two somatic cell hybrids between K562 and mouse erythroleukemia (MEL) cells, a human fetal liver x MEL somatic cell hybrid, and reticulocytes and bone marrow cells from normal adults. theta 1-Globin gene was expressed in all cell types. Inducible expression (two- to sixfold) was documented both in HEL and K562 erythroleukemia cells after 5 azacytidine treatment. Like K562 cells, HEL cells also displayed hemin-inducible theta 1-globin gene expression. Following transfer of human chromosome 16 from embryonic/fetal K562 to the adult MEL cells, theta 1-globin gene remained active but lost its potential for inducibility, suggesting probably a trans regulation mechanism. Higher levels of theta 1 mRNA were found in fetal liver cells compared with trace amounts in reticulocytes and normal adult bone marrow cells. These data clearly show that in contrast to the embryonic and adult patterns of expression of zeta and alpha-globin genes, respectively, theta 1-globin gene displays a different profile, being active predominantly during the early stages of ontogeny, switching to lower levels of expression in adulthood. PMID- 2239921 TI - Massive mediastinal extramedullary hematopoiesis in hereditary spherocytosis: a case report. AB - A case of extramedullary hematopoiesis (EMH) with a massive mediastinal mass in a 72-year-old woman with hereditary spherocytosis is reported. Several cases of EMH have been described in nonsplenectomized adults with hereditary spherocytosis, and it is thought to be a consequence of long-term stimulation of erythropoiesis. The exact mechanism remains controversial. EMH should be considered in the differential diagnosis of an asymptomatic paravertebral mass. PMID- 2239922 TI - Extranodal T-cell lymphoma mimicking malignant histiocytosis. AB - We report a case of extranodal T-cell lymphoma with fever, hepatosplenomegaly, pancytopenia, and diffuse sinusoidal infiltration of the spleen, liver, and bone marrow by the tumor cells, mimicking malignant histiocytosis. This is the second case of T-gamma (T-cell suppressor) lymphoma resembling the case reported by Kadin et al. [N Engl J Med 304:648, 1981]. The lack of lymph node involvement in this case supports the theory that this type of lymphoma arises in the spleen. This paper draws attention to the extranodal T-cell lymphoma groups that mimic malignant histiocytosis and the need of immunophenotyping for a correct diagnosis. The causes for the absence of T-cell receptor gene rearrangement in T cell tumors are discussed. PMID- 2239923 TI - Evaluation of an automated bleeding time device in the newborn. AB - Sick infants frequently developed impaired hemostasis as a secondary event. Abnormal platelet-vessel wall interaction contributes to the hemorrhagic side effects. Currently, the bleeding time is the best measure of in vivo platelet participation in small vessel hemostasis. Bleeding times in the newborn have been previously determined with an automated device designed for the adult or with nonautomated devices. The automated bleeding time device for the adult is not suitable for the infant (length 5 mm, depth 1 mm). We evaluated the performance of an automated bleeding time device designed specifically for the newborn making a cut 2.5 mm in length and 0.5 mm in depth. The results with the automated device showed a strong correlation with the modified template bleeding time device previously used for the newborn. The normal range was shorter and the sensitivity to abnormal vessel wall interaction was greater with the automated device. As well, the ease of determining the bleeding time with the automated device was considerably improved over the template device. PMID- 2239924 TI - Induction of alkaline phosphatase activity in chronic myeloid leukemia cells: in vitro studies and speculative hypotheses. AB - Three patients with Ph chromosome + chronic myeloid leukemia (CML) in chronic phase suffered from intercurrent pleuritis of undefined origin. At that time, leucocyte alkaline phosphatase activity (LAPA) score was low for circulating neutrophils, but high for those from pleural effusion. LAP negative circulating CML granulocytes were incubated with the pleural liquid: after 40-70 hr, almost all were intensely LAP positive. This finding suggests that the low LAPA score in resting CML neutrophils is attributable to the absence of appropriate stimuli rather than to an incapacity to synthesize the enzyme. PMID- 2239925 TI - Recurrent disseminated intravascular coagulation and fulminant intra hepatic thrombosis in a patient with the anti-phospholipid syndrome. AB - We describe a patient with the lupus anti-coagulant who had recurrent episodes, over a 2 year period, of a severe and disseminated intravascular coagulopathy. This patient also had positive serological assays for syphilis and anti cardiolipin antibodies. Associated with the coagulopathy were co-expressed episodes of liver disease, ultimately terminating in fulminant liver failure. At autopsy the features were characteristic of the Budd-Chiari syndrome. This is the first report to document how consumptive coagulopathy may present as a dominant feature of the anti-phospholipid syndrome. It also clearly describes an immune mediated thrombotic mechanism as a cause of hepatic veno-occlusive disorders. Furthermore, this case highlights the varied clinical spectrum of the anti phospholipid syndrome and suggests that a high index of suspicion is required to ensure its diagnosis. PMID- 2239926 TI - Necrobiotic xanthogranuloma with IgA multiple myeloma: a case report and literature review. AB - The association between necrobiotic xanthogranuloma of the dermis and paraproteinemia and/or B-cell malignancy is best described in the ophthalmologic literature. We report a case which occurred in the eyelid and orbit of a 64 year old man that led to the diagnosis of an IgA multiple myeloma. To our knowledge, this is the first report of an IgA type paraproteinemia and IgA type multiple myeloma associated with necrobiotic xanthogranuloma. PMID- 2239927 TI - A fatal case of low titer anti-PR cold agglutinin disease. AB - Cold agglutinin disease typically produces a low-grade hemolytic anemia. We describe herein the unusual occurrence of an anti-PR cold agglutinin with high thermal amplitude which caused significant and ultimately fatal hemolytic anemia at very low titers. PMID- 2239928 TI - High-dose methylprednisolone in children with acute nonlymphoblastic leukemia. PMID- 2239929 TI - Autosomal dominant polycystic kidney disease--more than a renal disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease, affecting a half million Americans. The clinical phenotype can result from at least two different gene defects. One gene that can cause ADPKD has been located on the short arm of chromosome 16. This discovery has made possible new methods for diagnosing the disorder in gene carriers prior to the development of renal cysts. Although renal cysts are clearly an important manifestation of the gene defect, other systemic manifestations are both common and clinically important. Cardiac valvular lesions, intracranial aneurysms, hepatic cysts, and diverticula are included in the array of systemic manifestations. Moreover, renal cysts are only one of a myriad of renal manifestations. Although ADPKD was long considered an adult cystic disease, it is also a common cause of childhood cystic disease and must be considered in the differential diagnosis in that setting. PMID- 2239930 TI - Cyclosporine nephrotoxicity and the role of cyclosporine in living-related donor transplantation. PMID- 2239931 TI - HLA-identical renal transplants: impact of cyclosporine on intermediate-term survival and renal function. AB - Seventy-two and 34 consecutive HLA-identical sibling renal transplant recipients were treated with azathioprine/prednisone (AZA; follow-up, 5.0 years) and cyclosporine/prednisone (CSA; mean follow-up, 2.9 years), respectively. Both groups were similar in age, sex, race, and number of transplants, but there were more diabetics in the CSA group (34% v 8%). Actual patient survival at 1 year and actuarial patient survival at 5 years were 100% and 96%, respectively in the CSA group compared with an actual patient survival of 91% and 82% at 1 and 5 years, respectively, in the AZA group. Actual graft survival at 1 year improved from 85% in the AZA group to 97% in the CSA-treated recipients (P less than 0.05). Mean serum creatinine at 5 years remained stable in the AZA group at a mean of 123 mumol/L (1.4 mg/dL) compared with a progressive increase in this parameter to a mean of 212 mumol/L (2.4 mg/dL) after the same time interval in the CSA patients. Furthermore, the slopes of the serum creatinine against time were significantly different between the two groups (P less than 0.01). Mean daily CSA dose averaged 4 mg/kg 12 months following transplantation, with a decrease to 2.4 mg/kg by the fifth year. Causes of death in the AZA group were cardiovascular (eight), sepsis (three), cancer (one); and in the CSA group, Kaposi's sarcoma (one). Causes of graft failure in the AZA group were immunological (six), sepsis (three), technical (two), recurrence of disease (one), and patient death with a functioning graft (five). Technical (one), noncompliance (two), recurrence of disease (one), and patient death with a functioning kidney (one) caused graft failure in the CSA group. No difference in posttransplantation serum cholesterol or incidence of new onset diabetes was observed between the two groups, but hypertension was significantly more frequent (51% v 21%, P less than 0.01) when CSA was used. In conclusion, intermediate-term results of CSA-treated HLA identical transplant recipients showed improved patient and graft survival with less complications apart from hypertension. However, the slow, but relentless, increase in serum creatinine in the CSA-treated patients compared with those treated with AZA is of concern. PMID- 2239932 TI - Extracorporeal removal of anti-HLA antibodies in transplant candidates. AB - We report on the results of a clinical trial in which 14 transplant candidates were treated with an extracorporeal immunoadsorption system using Protein A that selectively removes immunoglobulin from plasma; we also assessed the dynamics of anti-HLA antibody as a model of IgG removal and re-equilibration, as well as the clinical safety of the procedure. At the end of a treatment course, plasma IgG levels were reduced by 90% +/- 8% of control values (P less than 0.01). In contrast, albumin levels were reduced by only 15% (P less than 0.05). Specific cytotoxic anti-HLA antibody titers were reduced by approximately 18-fold. Panel reactivity was measured as the proportion of a 40-member cell donor panel killed by patients' serum in the presence of complement; in nine of the 14 patients, there was a significant reduction in this parameter (range, 23% to 87%). During the 4-week follow-up period, anti-HLA antibody titers returned to baseline levels. There were no remarkable changes observed in blood chemistries, nor were there any unanticipated adverse reactions seen in the patients treated. We conclude that selective extracorporeal immunoadsorption is a safe and effective way of removing IgG-type antibodies, with potential application to reduction of HLA antibodies in transplant candidates. PMID- 2239933 TI - Adult minimal change glomerulopathy with acute renal failure. AB - Oliguric acute renal failure occurs in some adult patients with minimal change glomerulopathy. To look for clinical and pathologic factors that increase the risk for developing acute renal failure, 21 adults with minimal change glomerulopathy and a serum creatinine greater than 177 mumol/L (mean, 486 mumol/L; range, 194 to 1,344 mumol/L) (greater than 2.0 mg/dL [mean, 5.5 mg/dL; range, 2.2 to 15.2 mg/dL]) were compared with 50 adults with minimal change glomerulopathy and a serum creatinine less than 133 mumol/L (mean, 88 mumol/L; range, 53 to 124 mumol/L) (less than 1.5 mg/dL [mean, 1.0 mg/dL; range, 0.6 to 1.4 mg/dL]). Minimal change glomerulopathy patients with acute renal failure were older (59.5 v 40.3 years, P less than 0.001), and had higher systolic blood pressure (158 v 138 mm Hg, P = 0.001), more proteinuria (13.5 v 7.9 g/24 h, P = 0.01), and more arteriosclerosis in the renal biopsy specimen (1.7 + v 0.7 + on a scale of 0 to 4+, P = 0.005). Tubular epithelial simplification identical to that observed with ischemic acute renal failure (acute tubular necrosis) was observed in 71% of the patients with serum creatinine greater than 177 mumol/L (greater than 2.0 mg/dL) and 0% of those with less than 133 mumol/L (less than 1.5 mg/dL). All 18 patients with renal failure for whom follow-up data were available had recovery of function (mean creatinine, 539 +/- 301 mumol/L [6.1 +/- 3.4 mg/dL] at the time of biopsy and 106 +/- 27 mumol/L [1.2 +/- 0.3 mg/dL] at last follow-up), but sometimes only after weeks of dialysis support.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239934 TI - Body fluid spaces and blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin. AB - Blood pressure (BP) may increase in hemodialysis patients during treatment of anemia with recombinant human erythropoietin (r-HuEPO). Since fluid volume is a determinant of BP in dialysis patients, changes in body fluid spaces during r HuEPO therapy could affect BP. Thus, 51Cr-labeled red blood cell (RBC) volume, inulin extracellular fluid (ECF) volume, and urea total body water (TBW), as well as cardiac output, plasma renin activity (PRA), and plasma aldosterone concentration were determined postdialysis before and after r-HuEPO therapy in patients in whom changes in BP could be managed by ultrafiltration alone. Eleven patients entered the study: one had a renal transplant and two required addition of antihypertensive drug therapy and were excluded; eight, of whom two required antihypertensive drug therapy following the study, were included in the analyses. Results revealed an increase in predialysis hemoglobin from 67 to 113 g/L (6.7 to 11.3 g/dL) (P = 0.001) during 18 +/- 6 weeks of therapy. Predialysis diastolic BP increased from 80 to 85 mm Hg (P = 0.07), while postdialysis diastolic BP was unchanged at 73 mm Hg. 51Cr-RBC volume increased, from 0.7 to 1.3 L (P = 0.004). ECF tended to decrease, from 13.7 to 10.8 L (P = 0.064), while TBW decreased to a similar extent, but not significantly, 34.3 to 31.2 L (P = 0.16). Postdialysis ECF volume was positively correlated with mean arterial BP at baseline (r = 0.89, P = 0.007) and after therapy (r = 0.74, P = 0.035). However, the regression lines for this relationship were different (P = 0.022) before and after therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239936 TI - Ten-year prospective study on the development of renal cell carcinoma in dialysis patients. AB - A prospective study was undertaken to investigate the development of renal cell carcinoma in dialysis patients. Three renal cell carcinomas were detected among 96 hemodialysis patients in 1979, and screening by computed tomographic (CT) scan was continued yearly until 1989. During this 10-year period, one renal cell carcinoma was found in the second year and another in the ninth year. Autopsy performed on seven of 19 patients who died showed one case of small clear cell carcinoma accompanying acquired cystic disease. In 33 males, kidneys were found to have enlarged 2.7 +/- 1.7 times over the 10-year follow-up due to acquired cysts, while no change in kidney volume was noted in 24 females. Native kidneys in nine of 12 patients who maintained functioning grafts were reduced in size. The patient with the largest kidney enlargement (11.5 times) died from retroperitoneal bleeding in 1989. These prospective study results suggest that both the incidence and prevalence of renal cell carcinoma in dialysis patients is high. Furthermore, major complications of acquired renal cystic disease seem to occur predominantly in males. PMID- 2239935 TI - Bioavailability of iron in hemodialysis patients treated with erythropoietin: evidence for the inhibitory role of aluminum. AB - The dose of recombinant human erythropoietin (r-HuEPO) required to correct the anemia of end-stage renal disease (ESRD) varies among patients. The response to r HuEPO is impaired if absolute or relative iron deficiency exists. Aluminum may cause a microcytic anemia in patients with ESRD, but the mechanism remains incompletely defined. Twenty-two patients in the Canadian Multicentre EPO trial were studied for 6 months. In this randomized double-blind placebo-controlled trial, free erythrocyte protoporphyrin (FEP) was used as an indicator of iron deficient deficient erythropoiesis. The relationship of FEP to the estimates of iron availability (serum iron, transferrin saturation, ferritin) and iron utilization (corrected reticulocyte count, hemoglobin) was evaluated by multiple linear regression analysis. The effect of aluminum on FEP was evaluated by adjusting the statistical model for this variable. All patients were iron replete as assessed by serum ferritin. FEP was not related to serum aluminum before administration of r-HuEPO, but it was significantly correlated with aluminum in the treated group. In hemodialysis patients treated with r-HuEPO, the proportion of the variability explained by the parameters of iron utilization and iron availability was 0.27. The effect of aluminum increased this to 0.59. In hemodialysis patients not receiving r-HuEPO, the proportion of variability in FEP explained by the model increased from 0.16 to 0.28 by adjusting for aluminum. The data support the hypothesis that aluminum interferes with the bioavailability of stored iron for erythropoiesis and thus may result in a microcytic anemia in patients with ESRD or may blunt their response to r-HuEPO therapy. PMID- 2239938 TI - Brachial-jugular polytetrafluoroethylene fistulas for hemodialysis. AB - A retrospective analysis was made of 16 patients who had received a brachial jugular polytetrafluoroethylene (PTFE) graft for hemodialysis. In four patients, the procedure was used to treat malfunctioning brachio-axillary fistulas due to long venous stenosis in the axillary vein. In 12 other patients, the operation was chosen in cases of exhaustion of the veins in the upper extremity because of previous multiple failed fistulas. Two patients died with a functioning fistula 7 and 10 months after placement of the graft of causes unrelated to the vascular access. The other 14 patients retained functioning fistulas between 8 and 26 months after construction of the shunt. Three patients needed graft thrombectomy to treat occlusive episodes. No venous stenosis was found in a postoperative fistulography made in those patients. One patient needed substitution of a graft segment due to stenosis of the prosthesis crossing over the clavicle. We believe that the brachial-jugular graft is a procedure that can be considered as vascular access for hemodialysis in cases where the use of veins in the upper extremity and the axilla is not possible. PMID- 2239937 TI - Etiology of hypercalcemia in hemodialysis patients on calcium carbonate therapy. AB - Fourteen of 39 dialysis patients (36%) became hypercalcemic after switching to calcium carbonate as their principal phosphate binder. In order to identify risk factors associated with the development of hypercalcemia, indirect parameters of intestinal calcium reabsorption and bone turnover rate in these 14 patients were compared with results in 14 eucalcemic patients matched for age, sex, length of time on dialysis, and etiology of renal disease. In addition to experiencing hypercalcemic episodes with peak calcium values of 2.7 to 3.8 mmol/L (10.7 to 15.0 mg/dL), patients in the hypercalcemic group exhibited a significant increase in the mean calcium concentration obtained during 6 months before the switch, compared with the mean value obtained during the 7 months of observation after the switch (2.4 +/- 0.03 to 2.5 +/- 0.03 mmol/L [9.7 +/- 0.2 to 10.2 +/- 0.1 mg/dL], P = 0.006). In contrast, eucalcemic patients exhibited no change in mean calcium values over the same time period (2.3 +/- 0.05 to 2.3 +/- 0.05 mmol/L [9.2 +/- 0.2 to 9.2 +/- 0.2 mg/dL]). CaCO3 dosage, calculated dietary calcium intake, and circulating levels of vitamin D metabolites were similar in both groups. Physical activity index and predialysis serum bicarbonate levels also were similar in both groups. However, there was a significant difference in parameters reflecting bone turnover rates between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2239939 TI - Adult and pediatric peritonitis rates in a home dialysis program: comparison of continuous ambulatory and continuous cycling peritoneal dialysis. AB - We reviewed our 115-month experience with continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) in adult and pediatric patients to determine whether there is a difference in the incidence of peritonitis between patients performing CAPD or CCPD. Peritonitis rates were similar in patients performing CAPD or CCPD in both the adult and pediatric age groups. The overall CAPD peritonitis rate was significantly lower in adult patients when compared with pediatric patients. There was no difference in peritonitis rates for CCPD between adult and pediatric patients. When the data are divided into 3-year subgroups, the incidence of peritonitis is significantly lower in adult patients undergoing either CAPD or CCPD when compared with pediatric patients during the years 1986 to 1988. There is significant improvement over time in the incidence of peritonitis in both adult and pediatric patients performing CCPD; similarly, there is a trend toward improvement in patients performing CAPD. Staphylococcus species organisms remain the most common bacterial cause of peritonitis, except in pediatric patients under the age of 2 years or with nephrostomies, where gram-negative rod infections were more common. Peritonitis resulted in discontinuation of peritoneal dialysis in a greater number of adult patients. These results suggest that the number of catheter manipulations is not important in determining the incidence of peritonitis. Pediatric patients are more likely than adult patients to develop peritonitis with either CAPD or CCPD. Adult patients are more likely than pediatric patients to discontinue peritoneal dialysis secondary to peritonitis. PMID- 2239940 TI - The renal concentrating defect associated with potassium depletion is independent of prostaglandin E2. AB - Prostaglandin E2 (PGE2) impairs the hydrosmotic effect of vasopressin in toad bladder and mammalian kidney. Because some studies in animals have suggested that potassium depletion enhances renal PGE2 production, the present study examined whether the renal concentrating defect of potassium depletion in humans is mediated by PGE2. Five normal volunteers were studied before and after moderate potassium depletion achieved by 10 days of dietary potassium restriction and administration of a polystyrene sulfonate potassium exchange resin (Kayexalate). Maximal urinary osmolality (Umax) decreased from 1,094 +/- 58 (mean +/- SEM) to 820 +/- 26 mmol/kg (mOsm/kg) (P less than 0.01) following potassium depletion, but urinary PGE2 excretion did not change (496 +/- 145 and 435 +/- 186 ng/d, respectively). Indomethacin suppressed PGE2 excretion significantly, but failed to increase Umax in either the normal or the potassium-depleted state (1,094 +/- 34 and 825 +/- 56 mmol/kg, respectively). It is concluded that the renal concentrating defect produced by moderate potassium restriction in humans is not mediated by PGE2. PMID- 2239941 TI - Ultrasonography in the differentiation of complicated and uncomplicated acute pyelonephritis. AB - Differentiation of uncomplicated pyelonephritis versus complicated pyelonephritis has always been problematic. No clear physical signs or symptoms are diagnostic. To study differences between the two, we retrospectively reviewed charts of patients admitted to Charity Hospital, New Orleans, with febrile urinary tract infections. Criteria for inclusion were pyuria, positive urinary culture, and signs or symptoms of pyelonephritis. All patients underwent renal ultrasonography (US) before other diagnostic tests. US identified a potential emergency (hydronephrosis or abscess) in 11 of 98 patients (11.2%). The only significant contributing factor was the presence of diabetes mellitus, which was present in five of 11 emergent conditions and eight of 73 of the remainder (P = 0.003). US is inexpensive, easily obtainable in the emergency room, and sensitive enough to screen patients with pyelonephritis for complications. However, we believe it is mandatory in diabetics, because of the high incidence of abnormalities in this population. PMID- 2239942 TI - Tubulointerstitial changes in systemic vasculitic disorders: a quantitative study of 18 biopsy cases. AB - Tubulointerstitial alterations were studied in 18 biopsy cases of systemic vasculitis. To evaluate the changes more objectively, two indexes, the number of interstitial inflammatory cells and tubulitis percentage, were used. The group means of both of these indexes were statistically higher than those of the autopsy control group, while 14 of the cases (77.8%) showed a significant difference (P less than 0.01) between individual means and the control group means. On the other hand, tubulointerstitial changes in systemic vasculitis seemed to be less prominent than drug-induced tubulointerstitial nephritis (TIN) according to these indexes. However, comparing these indexes with those of drug induced TIN, six cases (33.3%) of systemic angiitis could be regarded as having developed pathologic changes similar to TIN. Statistical difference was not shown in the indexes between those patients with histologic evidence of necrotizing angiitis and those without it. Clinically, urinary N-acetyl-beta-D glucosaminidase (NAG) was abnormally high in all three examined cases, reflecting the damage of renal tubular epithelial cells. Not only the vascular and glomerular lesions, but also tubulointerstitial changes, should be evaluated in the renal biopsy specimen of systemic vasculitis. PMID- 2239943 TI - The role of aluminum in the functional iron deficiency of patients treated with erythropoietin: case report of clinical characteristics and response to treatment. AB - The quantitative variation among patients in their response to erythropoietin can be explained, in part, by factors that can independently cause anemia in patients with end-stage renal disease. Aluminum can blunt the effect of erythropoietin, in part by interfering with iron bioavailability. This inhibitory effect cannot be completely overcome by aggressive ferrotherapy, but can be reversed with aluminum chelation therapy. A patient is described who developed hematological evidence of aluminum excess after being treated with erythropoietin. The biochemical evidence of functional iron deficiency and the response to aluminum chelation therapy support the hypothesis that the inhibitory effect of aluminum on erythropoiesis is mediated by the interference of aluminum with the bioavailability of iron. PMID- 2239944 TI - Temporary loss of limb function secondary to soft tissue calcification in a patient with rhabdomyolysis-induced acute renal failure. AB - A case of unusually severe soft tissue calcification with temporary loss of limb function in a patient with rhabdomyolysis-induced acute renal failure (ARF) is described. A large dose of intravenous (IV) calcium was administered early in the hospital course to treat hypocalcemia, and hemodialysis, when initiated, was with a 1.75-mmol/L calcium dialysate. This case illustrates the danger of administering calcium supplementation and raises questions about the use of normal to high dialysate calcium concentration in the early stages of rhabdomyolysis-induced oliguric ARF. Calcium supplementation should be reserved for patients with clear clinical signs of hypocalcemia and dialysate calcium should be adjusted to prevent excessive positive calcium balance. PMID- 2239945 TI - Does magnesium play a role in the hypokalemia of Bartter's syndrome? AB - A patient with Bartter's syndrome manifested hypomagnesemia in addition to hypokalemia. Under conditions of maximal free water production, he had a fractional distal solute reabsorption of 0.65, a value consistent with a renal defect in sodium chloride reabsorption in the thick ascending limb of the loop of Henle. This is also the site of 65% to 70% of urinary magnesium reabsorption. With magnesium supplementation and amiloride, the urinary potassium decreased and the serum potassium increased. Atrial natriuretic peptide concentrations in the plasma were low. Evaluation of family members showed five of nine offspring had hypokalemia with no disorder in the parents, an apparent autosomal recessive mode of inheritance. This is a US government work. There are no restrictions on its use. PMID- 2239946 TI - De novo crescentic glomerulonephritis in a renal transplant. PMID- 2239947 TI - The past and future of nephrology and urology. PMID- 2239948 TI - A personalized history of chronic hemodialysis. PMID- 2239949 TI - The roaring 50s: acute renal failure and dialysis of drugs, poisons, and nephrotoxins. PMID- 2239950 TI - The development of renal physiology since 1950. PMID- 2239951 TI - The application of micropuncture techniques to analysis of renal function: a personal view. PMID- 2239952 TI - The evolution of the science of pathologic physiology. PMID- 2239954 TI - Development of pediatric nephrology. PMID- 2239953 TI - The development of clinical renal transplantation. PMID- 2239955 TI - The development of urology as a scientific and clinical discipline. PMID- 2239956 TI - The development of renal pathology. PMID- 2239958 TI - The history and current status of continuous ambulatory peritoneal dialysis. PMID- 2239957 TI - The development of immunopathologic investigation of kidney disease. PMID- 2239959 TI - The development of percutaneous renal biopsy in man. PMID- 2239960 TI - The future of nephrology. AB - The Cellular and Molecular Age of Nephrology has dawned and the future is remarkably exciting. The successful attack on the major causes of renal disease, including genetic diseases, glomerulonephritis, diabetes, vasculitis, acute renal failure, and hypertension, will necessitate improved knowledge about pathogenesis. This new knowledge will allow early detection and target-specific therapies, the array of which is only limited by our imagination. The challenge to be an active player in this exciting future as a physician-scientist in the field of nephrology is indeed a rare opportunity. PMID- 2239961 TI - The future of urology. PMID- 2239962 TI - AJKD in retrospect: the first ten years. PMID- 2239963 TI - Epilogue: the National Kidney Foundation--its contributions to nephrology. PMID- 2239964 TI - The United States Renal Data System's 1990 Annual Data Report: an introduction. PMID- 2239965 TI - Recombination between two 14-bp homologous sequences as the mechanism for gene deletion in factor IX Seattle 1. AB - Factor IXSeattle 1 is a 10-kb intragenic deletion identified in a family that has hemophilia B. By sequencing across the site of the deletion, we discovered at the deletion junction a 13-bp sequence (5' . . . TAGAA-GTTCACTT . . . 3') that was homologous to two 14-bp sequences 10 kb apart in introns D and F of the normal factor IX gene. The presence of these homologous sequences in two different regions of the normal gene allows us to propose that genetic recombination has occurred between the sequences, resulting in the gene deletion. The precise recombination site was able to be localized to one of 5 bp (5' . . . AGTTC . . . 3') in the middle of the homologous sequences. The exact length of the deletion is 10,000 bp. PMID- 2239966 TI - Rapid detection of the hemoglobin C mutation by allele-specific polymerase chain reaction. PMID- 2239967 TI - The slash sheet: a simple procedure for risk analysis in cystic fibrosis. PMID- 2239968 TI - Family cell lines available for research. PMID- 2239969 TI - Genetic linkage and heterogeneity in type I Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type I). AB - The segregation patterns of DNA markers from the pericentromeric regions of chromosomes 1 and 17 were studied in seven pedigrees segregating an autosomal dominant gene for Charcot-Marie-Tooth neuropathy type I (CMT I; hereditary motor and sensory neuropathy I). A multilocus analysis with four markers (pMCR-3, pMUC10, FY, and pMLAJ1) spanning the pericentromeric region of chromosome 1 excluded the CMT I gene from this region in six pedigrees but gave some evidence for linkage to the region of Duffy in one pedigree. Linkage of the CMT I gene to markers in the pericentromeric region of chromosome 17 (markers pA10-41, pEW301, p3.6, and pTH17.19) was established; however, in these seven pedigrees homogeneity analysis with chromosome 17 markers detected significant genetic heterogeneity. This analysis suggested that three of the seven pedigrees are not linked to this same region. Overall, two of the seven CMT I pedigrees were not linked to markers tested from chromosomes 1 or 17. These results confirm genetic heterogeneity in CMT I and implicate the existence of a third autosomal locus, in addition to a locus on chromosome 17, and a probable locus on chromosome 1. This evidence of etiological heterogeneity, supported by statistical tests, will have to be taken into consideration when fine-structure genetic maps of the regions around CMT I are constructed. PMID- 2239970 TI - Localization of the microsatellite probe DXS426 between DXS7 and DXS255 on Xp and linkage to X-linked retinitis pigmentosa. AB - The microsatellite marker DXS426 maps to the interval Xp21.1-Xp11.21, the chromosomal region which contains two loci for X-linked retinitis pigmentosa (XLRP; RP2 and RP3). We have refined the localization of DXS426 both physically, by mapping it to a deletion which spans the interval Xp21.3-Xp11.23, and genetically, by studying multiply informative crossovers which indicate that DXS426 lies between DXS7 and DXS255 (i.e., Xp11.4-Xp11.22). As this is the region which contains the RP2 gene, RP2 families could be identified on the basis of linkage of XLRP to DXS426. Multiply informative crossovers in two RP2 families indicate that the most likely location of the RP2 gene is between DXS426 and DXS7. DXS426 is therefore an important highly informative marker for the purposes of carrier detection and early diagnosis of RP2 and for the localization of the disease gene. PMID- 2239972 TI - Multipoint analysis of human quantitative genetic variation. AB - A unique method of partitioning human quantitative genetic variation into effects due to specific chromosomal regions is presented. This method is based on estimating the proportion of genetic material, R, shared identical by descent (IBD) by sibling pairs in a specified chromosomal region, on the basis of their marker genotypes at a set of marker loci spanning the region. The mean and variance of the distribution of R conditional on IBD status and recombination pattern between two marker loci are derived as a function of the distance between the two loci. The distribution of the estimates of R is exemplified using data on 22 loci on chromosome 7. A method of using the estimated R values and observed values of a quantitative trait in a set of sibships to estimate the proportion of total genetic variance explained by loci in the region of interest is presented. Monte Carlo simulation techniques are used to show that this method is more powerful than existing methods of quantitative linkage analysis based on sib pairs. It is also shown through simulation studies that the proposed method is sensitive to genetic variation arising from both a single locus of large effect as well as from several loosely linked loci of moderate phenotypic effect. PMID- 2239971 TI - Autosomal dominant retinitis pigmentosa: absence of the rhodopsin proline--- histidine substitution (codon 23) in pedigrees from Europe. AB - In exon 1 at codon 23 of the rhodopsin gene, a mutation resulting in a proline-to histidine substitution has previously been observed in approximately 12% of American autosomal dominant retinitis pigmentosa (ADRP) patients. The region around the site of this mutation in the rhodopsin gene has been amplified and analyzed in affected individuals from 91 European ADRP pedigrees. The codon 23 mutation has been found to be absent in all cases, including a large Irish pedigree in which the disease gene has previously been shown to be closely linked to the rhodopsin locus. This indicates the presence of either allelic or nonallelic heterogeneity in ADRP. PMID- 2239973 TI - Replication patterns of the fragile X in heterozygous carriers: analysis by a BrdUrd antibody method. AB - The replication status of the fragile X chromosomes was studied in short-term cultures of lymphocytes from six female heterozygous carriers. The fragile X was induced by adding 0.1 microM fluorodeoxyuridine during the last 24 h of culturing. The replication status of the X chromosomes was studied using a bromodeoxyuridine (BrdUrd) antibody method. BrdUrd was added (1) at a final concentration of 0.2 micrograms/ml during the early S phase of chromosome replication (16-10 h before harvest), (2) at 0.2 microgram/ml during the late S phase (the last 6 h of culturing), (3) at 20 micrograms/ml during the early S phase, and (4) at 20 micrograms/ml during the late S phase. BrdUrd that was incorporated into replicating chromosomes was detected by using a nuclease and BrdUrd monoclonal antibody. The frequency of the fragile X was reduced by BrdUrd treatment. The degree of reduction was more severe in the 20 micrograms/ml than in the 0.2 microgram/ml series and was more severe with late S than with early S treatment. Of the early- and late-replicating fragile X chromosomes, those which were actively replicating during a BrdUrd treatment were more reduced than the others. Thus, the average rate of early and late S treatment with 0.2 microgram BrdUrd/ml was assumed to be the closest reflection of the situation in vivo. There was no correlation between the average rate of the early replicating, active fragile X and the intelligence of the heterozygous carriers studied. PMID- 2239974 TI - Intravenous immunoglobulin treatment for the chronic fatigue syndrome. PMID- 2239975 TI - A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. AB - PURPOSE: Currently, there is no established therapy for chronic fatigue syndrome (CFS), a recently defined illness that has been associated with a variety of immunologic abnormalities. Based on the hypothesis that a chronic viral infection or an immunoregulatory defect is involved in the pathogenesis of CFS, the therapeutic benefit of intravenous immunoglobulin G (IV IgG) was evaluated in a group of patients with CFS. Additionally, serum immunoglobulin concentrations and peripheral blood lymphocyte subset numbers were measured at the outset of the study, and the effect of IV IgG therapy on IgG subclass levels was determined. PATIENTS AND METHODS: Thirty patients with CFS were enrolled in a double-blind, placebo-controlled trial of IV IgG. The treatment regimen consisted of IV IgG (1 g/kg) or intravenous placebo (1% albumin solution) administered every 30 days for 6 months. Participants completed a self-assessment form prior to each of the six treatments, which was used to measure severity of symptoms, functional status, and health perceptions. Patients were also asked to report adverse experiences defined as worsening of symptoms occurring within 48 hours of each treatment. RESULTS: Twenty-eight patients completed the trial. At baseline, all 28 patients complained of moderate to severe fatigue, and measures of social functioning and health perceptions showed marked impairment. Low levels of IgG1 were found in 12 (42.9%), and 18 (64.3%) had low levels of IgG3. At the end of the study, no significant therapeutic benefit could be detected in terms of symptom amelioration or improvement in functional status, despite restoration of IgG1 levels to a normal range. Major adverse experiences were observed in 20% of both the IV IgG and placebo groups. CONCLUSION: The results of this study indicate that IV IgG is unlikely to be of clinical benefit in CFS. In addition to the ongoing need for placebo-controlled trials of candidate therapies for CFS, an expanded research effort is needed to define the etiology and pathogenesis of this disorder. PMID- 2239976 TI - A bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting anticoagulant therapy. AB - PURPOSE: To construct and test prospectively a bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting long-term anticoagulant therapy. PATIENTS AND METHODS: In an inception cohort of 617 patients starting long-term anticoagulant therapy in one hospital, data were gathered retrospectively and bleeding was classified using reliable explicit criteria. We constructed a bleeding risk index by identifying and weighting independent predictors of major bleeding using a multivariate proportional hazards model. The bleeding risk index was tested in 394 other patients prospectively identified in a second hospital. The index was compared to physicians' predictions. RESULTS: Major bleeding developed before discharge in 61 of all 1,011 patients (6%). The bleeding risk index included four independent risk factors for major in-hospital bleeding: the number of specific comorbid conditions; heparin use in patients aged 60 years or older; maximal prothrombin or partial thromboplastin time 2.0 or more times control; liver dysfunction worsening during therapy. In the testing group, the index predicted major bleeding, which occurred in 3% of 235 low-risk patients, 16% of 96 middle-risk patients, and 19% of 63 high-risk patients (p less than 0.001). The bleeding risk index performed as well as physicians' predictions, and integration of the bleeding risk index with physicians' predictions led to a classification system that was more sensitive (p = 0.03) than physicians' predictions alone. In 86% of patients with a high risk of major bleeding, we identified specific ways of improving therapy, e.g., avoiding overanticoagulation and nonsteroidal anti inflammatory agents. CONCLUSION: The bleeding risk index provides valid estimates of the probability of major bleeding in hospitalized patients starting long-term anticoagulant therapy and complements physicians' predictions. The possibility that bleeding can be prevented in high-risk patients warrants prospective evaluation. PMID- 2239977 TI - The importance of cytogenetic studies in adult acute lymphocytic leukemia. AB - PURPOSE: The prognostic importance of pretreatment bone marrow cytogenetic studies in adults with acute lymphocytic leukemia treated at a single institution, with an identical treatment program, is described. PATIENTS AND METHODS: A total of 105 patients with a documented morphologic diagnosis of acute lymphocytic leukemia were reviewed for the purpose of this analysis. All patients had an extensive workup at presentation, and cytogenetic analysis was performed in 103 patients, using the Giemsa banding technique with trypsin pretreatment on 24-hour cultured cells. RESULTS: The specific cytogenetic classification in the 103 patients who had the karyotypic analysis was as follows: diploid 27%; Philadelphia chromosome-positive 13%; hyperdiploid 12%; B-cell karyotype 6%; 6q- and 14q+ abnormalities 4%; pseudodiploid 8%; hypodiploid 2%; and insufficient metaphases 28%. B-cell, 6q- or 14q+, and Philadelphia chromosome-positive karyotypes tended to correlate with other known negative prognostic factors. Patients with diploid, hyperdiploid, pseudodiploid, and hypodiploid karyotypes or with insufficient metaphases could be combined into one group with a favorable prognosis. In this group, the remission rate with induction chemotherapy was 89%, the median complete remission duration was 26 months, and the median survival was 25 months, with a 3-year survival rate of 45%. Patients with Philadelphia chromosome-positive, B-cell, and 6q- or 14q+ abnormalities collectively had an unfavorable prognosis. Their response rate to induction chemotherapy was 65%, the median response duration was 7 months, and the median survival was 8 months, with a 3-year survival rate of less than 10%. CONCLUSION: We conclude that the pretreatment bone marrow karyotype is an important part of the evaluation of adults with acute lymphocytic leukemia and provides significant prognostic information. PMID- 2239978 TI - Sudden death in young competitive athletes: clinicopathologic correlations in 22 cases. AB - PURPOSE: To investigate the pathologic substrates of sudden death in young competitive athletes. PATIENTS AND METHODS: Twenty-two cases of sudden death in young competitive athletes occurring in the Veneto region (northern Italy) in the period January 1979 to December 1989 were studied by postmortem examination. The athletes included 19 males and three females, ranging in age from 11 to 35 years (mean, 23 years). RESULTS: In 18 cases, sudden death occurred during (16 cases) or immediately after (two cases) a competitive sport activity. In 10 subjects, sudden death was apparently the first sign of disease. Postmortem examination disclosed that this fatality was due to arrhythmic cardiac arrest in 17 cases; among these, right ventricular cardiomyopathy, also known as "right ventricular dysplasia," was the most frequently encountered cardiovascular disease (six cases), followed by atherosclerotic coronary artery disease (four cases), conduction system pathology (three cases), anomalous origin of right coronary artery from the wrong aortic sinus (two cases), and mitral valve prolapse (two cases). In two athletes, the abrupt lethal complication was "mechanical" and consisted of pulmonary embolism and rupture of the aorta; in three athletes, death was due to a cerebral cause. All athletes with right ventricular cardiomyopathy died during effort, and most had a history of palpitations and/or syncope. Whenever available, electrocardiographic (ECG) tracings showed inverted T waves in precordial leads and/or left bundle branch block ventricular arrhythmias. CONCLUSIONS: Clinicopathologic correlations indicate that in the Veneto region of Italy, right ventricular cardiomyopathy is not so rare among the cardiovascular diseases associated with the risk of arrhythmic cardiac arrest, and seems to account for the majority of cases of sudden death in young athletes; this disorder can be suspected during life on the basis of prodromal symptoms and ECG signs. PMID- 2239979 TI - Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter. AB - PURPOSE: To test the hypothesis that during the natural history of sporadic nontoxic goiter (SNG), a diffuse goiter precedes a multinodular goiter with gradual development of autonomous thyroid function. PATIENTS AND METHODS: A cross sectional survey of 102 consecutive patients with SNG (seven male, 95 female) was performed. Thyroid volume was measured by ultrasonography, and plasma thyroid stimulating hormone (TSH) by a sensitive assay (TSH immunoradiometric assay). RESULTS: Patients with a multinodular goiter were older and had a larger thyroid volume than patients with a diffuse or uninodular goiter. Plasma free thyroxine (T4) and total triiodothyronine (T3) were higher and plasma TSH was lower in patients than in normal subjects. Free T4 was higher in the subgroup of patients with a multinodular goiter and a decreased TSH response to thyrotropin-releasing hormone. Plasma TSH (y, in mU/L) was negatively related to thyroid volume (x, in mL): y = 8.2x-0.667 (r = 0.578, p less than 0.001). Thyroid volume (y, in mL) was positively related to age (x, in years): y = -21.8 + 2.0x (r = 0.455, p less than 0.001); and to duration of goiter (x, in years): y = 40.6 + 2.1x (r = 0.505, p less than 0.001). The annual increase in thyroid volume was calculated at 4.5%. CONCLUSION: The data suggest a continuous growth of SNG and provide support for the concept of increasing thyroid nodularity and autonomy of thyroid function- related to increasing thyroid volume--during the natural history of this disorder. PMID- 2239980 TI - Beta 2-microglobulin predicts survival in primary systemic amyloidosis. AB - PURPOSE: The study assessed whether beta 2-microglobulin levels predict survival or response in patients with primary systemic amyloidosis without associated multiple myeloma. PATIENTS AND METHODS: The study group consisted of 131 untreated patients with biopsy-proven primary systemic amyloidosis diagnosed and evaluated at the Mayo Clinic. No patient had multiple myeloma. The minimum follow up of surviving patients is 8 years. No patient was lost to follow-up. RESULTS: The median survival of patients with an increased beta 2-microglobulin level was 10.8 months, compared with patients with a normal beta 2-microglobulin level (less than or equal to 2.7 micrograms/mL, 0.23 mumol/L) of 32.9 months (p less than 0.001). In a multivariate proportional-hazards model, the best model included congestive heart failure (p less than 0.0001) and increased beta 2 microglobulin levels (p less than 0.05). After adjustment for the presence of congestive heart failure, beta 2-microglobulin level remained significant. When the analysis was restricted to those patients with normal renal function, the median survival of those with an elevated beta 2-microglobulin level was 9.1 months versus 39.4 months for those with a normal level (p less than 0.001). The serum level of beta 2-microglobulin was increased in patients with nephrotic range proteinuria with or without renal insufficiency (p = 0.05). CONCLUSION: The serum beta 2-microglobulin level should be measured routinely in all patients with primary systemic amyloidosis because it provides a useful objective factor to identify subsets of patients with this disease who have unfavorable outcomes. PMID- 2239981 TI - Contrast nephropathy in azotemic diabetic patients undergoing coronary angiography. AB - PURPOSE: To evaluate the incidence of, risk factors for, and outcome of contrast nephropathy in azotemic diabetic patients undergoing coronary angiography. PATIENTS AND METHODS: Fifty-nine insulin-dependent diabetics with a mean serum creatinine level of 522 mumol/L (5.9 mg/dL) underwent coronary angiography as part of a pretransplant evaluation. Twenty-four azotemic diabetics undergoing inpatient evaluation not including angiography for transplantation formed the control group. Serum creatinine measurements obtained at baseline and after radiocontrast exposure were compared in patients and control subjects. Risk factors for contrast nephropathy were evaluated in patients with a 25% or greater increase in serum creatinine. RESULTS: Serum creatinine was significantly elevated 24 hours after radiocontrast exposure in patients (557 +/- 141 mumol/L versus 522 +/- 141 mumol/L, mean +/- SD; p less than 0.001) but not in controls. Seven patients required dialysis within 6 days of coronary angiography and two additional patients required dialysis within 14 days. Contrast nephropathy, defined as a serum creatinine increase of greater than 25% when measured 48 hours after radiocontrast exposure, occurred in 50% of patients and no controls. Univariate analysis of risk factors for contrast nephropathy revealed a significant association with dye quantity (p = 0.002), mean arterial pressure less than 100 mm Hg (p = 0.02), and ejection fraction less than 50% (p = 0.04). Stepwise logistic regression verified the independence of dye quantity and low mean arterial pressure but not low ejection fraction as risk factors for contrast nephropathy. Follow-up serum creatinine values were not significantly different in patients and control subjects. CONCLUSIONS: Azotemic patients with diabetes are at high risk of developing contrast nephropathy even when less than 100 mL of radiocontrast agent is used. The acute renal failure is reversible but precipitates the need for short-term dialysis in some patients. Radiocontrast quantity is an important risk factor not previously noted. The incidence of contrast nephropathy can be minimized by using less than 30 mL of radiocontrast agent. PMID- 2239982 TI - Interleukin-1: biology, pathophysiology, and clinical prospects. AB - Interleukin-1 (IL-1) is a cytokine with multiple biologic activities. Since its first description in 1972, significant work has been done, leading to an understanding of the biology of IL-1, which plays a central role in many important functions of the immune system. The biologic activities of IL-1 make it an attractive factor for use in clinical oncology, both as an antitumor agent and for the hematologic recovery of cancer patients receiving other forms of therapy. In this review the biologic effects of IL-1 are summarized. The possible involvement of IL-1 in the pathogenesis of some diseases is reviewed. Future prospects for the use of IL-1 in the treatment of malignancies are discussed. PMID- 2239983 TI - Liability issues and assessment of decision-making capability in nursing home patients. PMID- 2239984 TI - Myocardial infarction, cardiomyopathy, and interstitial lung disease in a 38-year old man. PMID- 2239985 TI - Preleukemic state preceding adult acute lymphoblastic leukemia. PMID- 2239986 TI - A new familial immunodeficiency disorder characterized by severe neutropenia, a defective marrow release mechanism, and hypogammaglobulinemia. PMID- 2239987 TI - Visceral leishmaniasis with malabsorption syndrome in a patient with acquired immunodeficiency syndrome. PMID- 2239988 TI - HTLV-I-associated adult T-cell leukemia/lymphoma presenting with nodular synovial masses. PMID- 2239990 TI - Increased urinary phosphoethanolamine in a man with asymptomatic osteopenia. PMID- 2239989 TI - Hepatitis-related hepatic erythropoietin production. PMID- 2239992 TI - Carcinoid tumor metastatic to the heart. PMID- 2239993 TI - Addison's disease and sarcoidosis: unusual frequency of co-existing hypothyroidism (Schmidt's syndrome) PMID- 2239991 TI - Medullary carcinoma of the thyroid in a patient treated for Hodgkin's disease. PMID- 2239994 TI - Liver biopsy in patients with serum antibodies to HIV. PMID- 2239995 TI - Antibiotic-related adverse effects in patients with leukemia. PMID- 2239996 TI - Cardiomyopathy related to thyroid dysfunction. PMID- 2239997 TI - Symptomatic hyponatremia. PMID- 2239998 TI - Is ovarian hemorrhage the full explanation of unexplained bleeding in a patient with mechanical valve prostheses? PMID- 2239999 TI - Diarrhea precipitated by oral liquid medication. PMID- 2240000 TI - Incidence of post-phlebitic syndrome after streptokinase therapy for deep vein thrombosis. PMID- 2240001 TI - Extrahepatic cholestasis as a distinct factor predisposing to gentamicin nephrotoxicity. PMID- 2240003 TI - Measurement of plasma active renin by solid phase radioimmunoassay using monoclonal antibodies. AB - A direct radioimmunoassay (RIA) for plasma active renin concentration (ARC) was evaluated by using plasma samples obtained from hospitalized normal volunteers and hypertensive patients. The direct renin RIA was performed by using a pair of anti-renin monoclonal antibodies and a sandwich method. It is suggested that an agitator should be used during the incubation, because the magnetic solid phase was precipitated and could not be suspended well in plasmas. Further, the thawed reagents should not be used for the assay. A highly significant correlation (r = 0.96, p less than 0.01) was found between ARC and enzymatic activity of renin (PRA) in plasma samples obtained from hypertensive patients. The mean values of ARC were 22.8 +/- 3.6 pg/ml in normal subjects, 22.5 +/- 5.3 in patients with EH having medium levels of PRA, 113.7 +/- 11.7 in patients with renovascular hypertension, and undetectable in patients with primary aldosteronism. The results indicated good and reliable performance of the direct renin RIA, which is clinically useful to investigate the renin-angiotensin system. PMID- 2240002 TI - Effects of calcium channel blockade on calcium homeostasis in mild to moderate essential hypertension. AB - Calcium channel blockers may alter parathyroid hormone secretion in vitro, which would alter calcium homeostasis. To determine the chronic effect of calcium channel blockade in vivo, we conducted a randomized, double blind, 16 week study comparing the effects of two pharmacologic antihypertensive agents, the calcium channel blocker diltiazem and the angiotensin-converting enzyme inhibitor captopril on parameters of calcium homeostasis. Both diltiazem and captopril lowered blood pressure to a similar degree. Neither drug produced any significant change in blood levels of total and ionized calcium, magnesium, or phosphorus, which affect the regulation of parathyroid hormone and vitamin D. In addition, at eight or 16 weeks following initiation, neither drug altered the serum levels of parathyroid hormone (PTH) or 1,25-(OH)2-vitamin D3 (1,25-D). Chronic calcium channel blockade with diltiazem does not alter serum parameters of calcium homeostasis and, thus, should not affect bone mineralization. PMID- 2240004 TI - Indomethacin increases plasma growth hormone levels in man. AB - In seven normal volunteers, the basal and arginine-stimulated levels of plasma growth hormone, glucose, glucagon, and free fatty acids and serum insulin was determined during placebo and during indomethacin 25 mg four times daily. Basal plasma growth hormone was higher during indomethacin (5.4 +/- 1 vs 1.7 +/- 2 ng/ml, p less than 0.005), as was the mean integrated response to intravenous arginine (40 +/- 14 vs 6 +/- 4 ng.min/ml, p less than 0.05). Despite lack of effect on plasma glucagon, indomethacin decreased the insulin response to arginine. The fall in free fatty acids during arginine infusion was decreased by indomethacin, which may in part be due to increased plasma growth hormone levels. In view of the many patients treated with indomethacin, the effect on growth hormone may be of clinical importance. PMID- 2240005 TI - Clinical and manometric aspects of diffuse esophageal spasm in a cohort of subjects evaluated for dysphagia and/or chest pain. AB - Manometric criteria for diffuse esophageal spasm have recently been restated. In this study, a cohort of 358 subjects was evaluated in a gastrointestinal motility laboratory for dysphagia and/or chest pain. Applying the recently proposed criteria of Richter and Castell, 18 subjects (5%) were diagnosed as having DES. Dysphagia was the major complaint (89%), while 44% of patients complained of chest pain and 33% of both symptoms. All patients shared more than 30% simultaneous contractions after wet swallows interspersed with normal peristaltic sequences. Associated manometric findings were repetitive (greater than 3 peaks) contractions (67%), high-amplitude contractions (33%), spontaneous activity (22%), prolonged duration (11%), and lower esophageal sphincter abnormalities (5%). Radiology disclosed significant abnormalities in only 27% of DES patients. PMID- 2240006 TI - An assault on old friends: thiazide diuretics under siege. AB - The adverse biochemical effects of thiazide use are of uncertain clinical significance. Thiazides raise LDL cholesterol only slightly in long-term studies and do not decrease HDL cholesterol. The evidence linking thiazide-induced hypokalemia with arrhythmias and sudden death is tenuous at best. Thiazide diuretics cause glucose intolerance, but no strong evidence has been advanced to suggest that this is dangerous. Because these effects are probably related to hypokalemia, a randomized trial comparing the effects of thiazides with thiazides plus a potassium-sparing diuretic on LDL cholesterol, ectopy on 48 hour ambulatory cardiac monitoring, fasting glucose and insulin, and post-glucose tolerance glucose and insulin would be of interest. The most compelling reason for continuing to use thiazides is that they have been shown in long-term randomized studies to reduce cardiovascular risk. Beta-blockers are the only other class of anti-hypertensive agent for which this claim can be made. The importance of long-term clinical trials in assessing the efficacy and toxicity of therapeutic agents is illustrated by the study that found clofibrate reduced cholesterol levels and coronary disease but increased total mortality. This finding remained undetected until a large randomized long-term trial was completed. Thiazide diuretics have not reduced the rate of coronary disease to the degree expected from epidemiologic studies, but the short length of the randomized trials may be responsible. It is not clear that other anti hypertensive agents will be superior. Thiazides are less expensive than other anti-hypertensive agents being touted as metabolically safer; the cost issue is not a trivial matter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240007 TI - Hematopoietic growth factors: overview and clinical applications, Part I. AB - The growth and differentiation of blood cells is regulated by a group of at least 12 glycoproteins, collectively known as hematopoietic growth factors. Advances in protein biochemistry and molecular genetics have provided the tools for the bulk production of these hormones for clinical application. Clinical trials of macrophage colony-stimulating factor, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and interleukin-3 have all demonstrated significant effects on the peripheral blood counts of the recipients. The clinical usefulness of these agents in ameliorating post chemotherapy myelosuppression, in the treatment of other cytopenias, and in enhancing engraftment after bone marrow transplantation has already been demonstrated. Potential applications to the therapy and diagnosis of other clinical disorders is under study. The history of the elucidation of these growth factors, our current understanding of their properties, interactions, and clinical effects, and the potential prospects for their future use in the manipulation of human blood cell production are the subject of this review. PMID- 2240008 TI - Symposium introduction: technology assessment and guideline development: concerns and opportunities for academic general internists. PMID- 2240009 TI - Practice standards: implications for the internist. AB - Pressure for national standards of medical practice is increasing from cost control initiatives, medical malpractice liability, and the desire to simplify complex practice problems. Good standards need to be academically sound, focused enough to be clinically useful, yet flexible enough to allow for the realities of practice. Standards have already been created by several professional societies, including anesthesiology and cardiology in internal medicine. Although physician education is primary, controlling the use of expensive new technologies is an unwritten but important secondary goal. While standards have reduced malpractice liability in some professional groups, some clinicians are concerned that standards will be too academic and unrealistic. Currently, third-party payers are watching the development of practice standards but are hesitant to use them as criteria for determination of reimbursement. The federal government has a major interest in practice standards as a means of both monitoring quality of care and controlling costs. A number of agencies are studying the development of standards and their implications for use. Recent articles questioning the usefulness of common diagnostic tests and even the routine physical examination have raised concern among internists that restriction of practice and reimbursement will follow. Some evolving standards, such as screening for breast cancer, seem to ignore the realities of clinical practice and may generate more cost than they save. Internists need to provide input as standards are developed to guarantee appropriateness and feasibility. PMID- 2240011 TI - Decision making at the bedside: lessons for clinical policy development. PMID- 2240010 TI - Entering the quality assurance decade. PMID- 2240012 TI - Federal involvement in technology assessment: a primer. PMID- 2240013 TI - Primary hyperaldosteronism. PMID- 2240014 TI - Reliability of cell counts and protein determinations in serial bronchoalveolar lavage procedures performed on healthy volunteers. AB - We measured the variability in volume, total cells, cell types, and proteins in the bronchoalveolar lavage fluid recovered from 10 volunteers (five smokers, five non-smokers) lavaged repeatedly over a three-year period. Thirty lavages were performed using a rigorously standardized approach. Differential counts on the cytospin preparations were performed by three independent readers and interobserver variability in the interpretation of these counts measured. Variability in interpreting the cellular counts was less in smokers than non smokers and decreased as the number of cells of any particular type increased. Only one reader interpreting the mean percentage of cells recovered of one cell type (neutrophils) in only one smoking group, the nonsmokers, was significantly different from the other two. There was also considerable variability in bronchoalveolar lavage fluid total protein, albumin, IgG, and IgA. Expressing albumin and IgG as a percentage of total protein recovered and expressing IgA and albumin as a ratio in nonsmokers lessened the variability of these parameters. Mean and standard deviations of the cellular and protein concentrations showed that large differences in these parameters would be necessary in order to attribute these changes to changes in the underlying pulmonary status. Excessive variability in nearly all parameters in this group without recognized lung disease challenges the usefulness of this test in the clinical assessment of patients serially followed because of underlying lung disease. PMID- 2240015 TI - Epidemiology of Lyme disease in Virginia. AB - Prior to January 1986, only one case of Lyme disease was reported from Virginia. In 1986-87, however, the Virginia Department of Health observed an increase in reports of suspected Lyme disease by physicians, despite the fact that Ixodes dammini is not highly prevalent in the Virginia tick population. Twenty-eight cases of Lyme disease were identified in Virginia, of which eight cases occurred in 1986 and 20 in 1987. Lyme disease appears to be increasing in frequency in Virginia and moving southward along the Eastern Atlantic Seaboard. PMID- 2240016 TI - A simplified technique for the production of heart failure in the dog by rapid ventricular pacing. AB - Prolonged rapid ventricular pacing (VP) in dogs produces low output heart failure (HF) characterized by cardiomegaly, ascites, and elevated plasma renin and norepinephrine levels. Commercially available pacemaker generators have a protective circuit that prevents pacing at rapid rates. Previously, investigators have had to use either external temporary pacemakers or customized generators to pace at rates greater than 130 beats per minute (bpm). The authors have developed a simple method to perform rapid VP by gluing magnets on Medtronic VVI generators, which allows programming in a temporary mode to sustain rates up to 400 bpm. Our results using 10 generators in 55 dogs demonstrates that HF is produced in all dogs when VP is maintained at 250 bpm for an average of 28 days. Technical difficulties during our early experience with this technique included magnets becoming unglued, loss of capture, and wound complications requiring generator removal. Thus, our method reuses commercially available generators to rapidly pace the ventricles and induce HF. PMID- 2240017 TI - Serum aldolase isozyme levels in patients with cerebrovascular diseases. AB - A subunit specific radioimmunoassay was developed for the quantification of human aldolase A, B, and C. The method used was a double antibody radioimmunoassay using radioiodinated purified aldolase A, B, or C subunits as the ligand, specific chicken antibodies to aldolase isozymes and rabbit antibodies to chicken IgG. The Iodogen method was used for iodination of the purified isozyme subunits in this study. Human brain tissue contained similar concentrations of aldolase A and aldolase C, and a smaller amount of aldolase B, which was the main isozyme of liver tissue. Levels of serum aldolase A were greater than 203 ng/ml, the upper limit of normal, in six of 24 patients with cerebral infarction and in 11 of 31 patients with cerebral hemorrhage. Nine of 24 patients with cerebral infarction and 16 of 31 patients with cerebral hemorrhage had serum aldolase C levels greater than 4.1 ng/ml, the upper limit in normal sera. These data suggest that serum aldolase C may be a more specific and sensitive marker of cerebrovascular diseases than aldolase A. We also demonstrated that serial measurement of serum aldolase C in patients with cerebrovascular diseases might be useful in estimating prognosis, since serially increasing serum aldolase C levels during the course of these diseases were correlated with a high mortality rate. PMID- 2240018 TI - Use of intrapleural streptokinase in the treatment of thoracic empyema. AB - The incidence of pleural effusions in bacterial pneumonia may exceed 40%, a factor that may be related to increased morbidity and mortality. Options in the treatment of complicated pleural effusions or empyema, when unresponsive to closed tube drainage, include repositioning of the indwelling tube thoracostomy or insertion of additional chest tubes, instillation of intrapleural streptokinase, and surgical intervention. The authors describe the course of three patients wherein the use of intrapleural streptokinase was efficacious in effecting prompt drainage of previously inadequately evacuated empyema, thus eliminating the necessity for further invasive intervention. PMID- 2240019 TI - Molecular biology in cardiology: recent developments and opportunities for clinical applications. AB - The revolution in molecular biology that has taken place in the last decade has provided powerful research methods that are changing our understanding of cardiovascular physiology and disease. This editorial commentary will highlight several areas of current research activity within the broad and expanding field of molecular cardiology, with a special emphasis on prospects for clinical applications in cardiovascular medicine. PMID- 2240020 TI - Production of transgenic mice and application to immunology and autoimmunity. AB - During the last decade, transgenic animal technology has assumed an increasingly important role as a critical tool in animal biology, biomedical research, and pharmaceutical development. This technology allows virtually any fragment of DNA large enough to contain an entire gene to become integrated into the germline of the recipient animal. The newly inserted DNA will be inherited like endogenous genes, and will be expressed as RNA and protein at tissue locations and abundance depending on regulatory elements attached to the coding DNA. It is possible to clone a particular gene, change a regulatory coding sequence, and reinsert the gene to determine the effect of the change on expression and function of the gene. PMID- 2240021 TI - Pulmonary disease in AIDS patients. AB - Pulmonary disease remains a major complication of the human immunodeficiency virus (HIV). Over the past decade several changes in the pattern of disease have occurred. Pneumocystis carinii pneumonia (PCP) remains the most common opportunistic pathogen in AIDS patients, though its incidence on bronchoscopy has declined and empiric therapy often occurs without a specific diagnosis. Changes in the management of patients with PCP have included different dosages and routes of administration for chemotherapy, improved overall survival, and a recent increase in the number of patients surviving episodes of respiratory failure. In addition, infection with mycobacteria tuberculosis (M.Tb.) has emerged as a major public health problem. The pattern of M.Tb. is distinct from non immunocompromised patients though response to therapy usually occurs. PMID- 2240022 TI - Urinary tract anomalies associated with congenital diaphragmatic defects. AB - Anomalies of the urinary tract occur in some 13-27% of infants with congenital posterolateral diaphragmatic defect (CDD) and are often severe (renal agenesis, dysplasia, hypoplasia, or hydronephrosis). To test the hypothesis that urinary and diaphragmatic anomalies share elements of pathogenesis, we reviewed 60 autopsy cases of CDD studied at our institution. Sixteen patients (27%) manifested anomalies of the urinary tract: 12 had markedly altered kidneys, 8 of which were unilateral and ipsilateral to the diaphragmatic defect. Among 27 patients free of gross urinary tract anomalies, kidney weights formed a skewed distribution, with most values above published norms for body weight; by analysis of covariance, kidney weight (as a function of body weight) was significantly greater in CDD than in a control population of infants free of chronic illnesses and congenital anomalies who died suddenly and unexpectedly. Differences in glomerular number and diameter could not be identified between the latter groups. In 71% of patients with isolated left CDD, the left kidney was heavier than the right, a reversal of the usual condition in infancy. These findings demonstrate that both marked and subtle changes of the urinary tract in CDD are generally ipsilateral to the diaphragmatic defect and suggest that the pathogenetic mechanisms responsible for urinary and diaphragmatic anomalies may overlap topographically. Aberrant morphogenesis within a developmental field or fields is one explanation for this. PMID- 2240023 TI - Mesomelic dysplasia with absence of fibulae and hexadactyly: Nievergelt syndrome or new syndrome? AB - Mesomelic dysplasia is a form of short-limb dwarfism characterized by disproportionate shortness of the middle segment of all limbs. Included in this category of skeletal disorders is the Nievergelt syndrome, which typically manifests a rhomboidal shape of the tibiae and fibulae, an unusual foot deformity, radioulnar synostosis, and dysplasia of the elbow and knee joints. We describe a patient with mesomelic dysplasia with findings suggestive of the Nievergelt syndrome and with absence of fibulae and hexadactyly. PMID- 2240024 TI - Rokitansky sequence in association with the facio-auriculo-vertebral sequence: part of a mesodermal malformation spectrum? AB - We report on a 4-year-old first-born monozygotic twin girl with a hypoplastic left face, mandible and zygoma, left microtia without an external auditory canal, a U-shaped cleft palate, right ectopic-fused kidneys, a blindly ending vaginal pouch, and absent uterus. We review 3 other cases with the manifestations of the Rokitansky and the facio-auriculo-vertebral sequence. The anomalies in these disorders can be thought of as deriving from an early defect or disruption in fetal mesoderm or its progenitor tissue at the time of primitive streak formation. They are frequently associated with other mesodermally derived defects or sequences and may together represent an extended polytopic field defect. While such speculation on how these spatially separated anomalies develop is probably simplistic, the concept of a mesodermal "malformation" spectrum is helpful in reminding the clinician to look for other mesodermal defects when one mesodermally derived defect or sequence is detected. PMID- 2240025 TI - Transient hypoglycemia with hyperinsulinemia in a newborn infant with Rubinstein Taybi syndrome. AB - A newborn boy with Rubinstein-Taybi syndrome who had profound neonatal hypoglycemia is presented. The infant was a discordant fraternal twin with intrauterine growth retardation. The hypoglycemia was due to transient hyperinsulinemia, a condition often seen in small-for-gestational-age infants. Neonatal hypoglycemia may be common in infants with Rubinstein-Taybi syndrome, especially if they also have intrauterine growth retardation. PMID- 2240026 TI - The syndrome of Hirschsprung disease, microcephaly, unusual face, and mental retardation. AB - Here we report on a boy with Hirschsprung megacolon associated with microcephaly, narrow palpebral fissures, broad nasal bridge, congenital heart defect, cryptorchidism, wide-base gait, short stature, developmental delay and abnormal computed tomography (CT) brain scan. The findings are compared with those of previously described patients with the same syndrome. PMID- 2240027 TI - The Cohen syndrome: does mottled retina separate a Finnish and a Jewish type? AB - A new familial cases of the Cohen syndrome in two brothers of one-half second cousin parents is reported. Typical clinical manifestations of the syndrome; i.e., mental deficiency, hypotonia, characteristic facial appearance, long, narrow hands and feet with elongated fingers, and mottled retinae were present in both patients. Both patients also had leukopenia. Clinical manifestations of the Cohen syndrome in patients are highly variable, and mottled retina has been observed in 22 of 87 patients (25%). However, an association of mottled retina in patients with the Cohen syndrome is likely to be related to the families and ethnic groups. Among 19 familial cases, mottled retina was observed in all affected sibs from five families, but in 13 families none of the affected sibs had the mottled retina. All Finnish patients had the mottled retina, but this was noted in only one of 39 Jewish patients. Based on these data, we hypothesize that two alleles at the gene locus for the Cohen syndrome exhibit different clinical manifestations: one is a Finnish type with mottled retina, and the other is a Jewish type without retinal anomalies. PMID- 2240028 TI - Lambotte syndrome: microcephaly, holoprosencephaly, intrauterine growth retardation, facial anomalies, and early lethality--a new sublethal multiple congenital anomaly/mental retardation syndrome in four sibs. AB - We report on an Arabic sibship originating from Morocco in which four children manifest an undiagnosed sublethal multiple congenital anomaly/mental retardation (MCA/MR) syndrome of intrauterine growth retardation (IUGR), microcephaly, large soft pinnae, telecanthus or true hypertelorism with squint, flat face, unusual hooked nose, very narrow mouth, retrognathia, and extremely severe neurologic impairment. One child was stillborn. Three others died in a cachectic state during their second year. One child had a severe cerebral malformation compatible with semilobar holoprosencephaly. Other inconstant manifestations are anterior chamber cleavage defect, preaxial polydactyly of feet, interventricular septal defect, and atresia of the external auditory meatus. Autosomal recessive inheritance is likely. PMID- 2240030 TI - Limb reduction defects and renal dysplasia: confirmation of a new, apparently lethal, autosomal recessive MCA syndrome. AB - We report on 2 sibs, a male and a female, who died shortly after birth from respiratory failure. They combined growth retardation with a Potter-like face, complete phocomelia of the upper limbs, rib anomalies (mainly severe hypoplasia of the 6 upper ribs), renal dysplasia, and external genital abnormalities. We hypothesize that these cases represent evidence for the existence of the "new syndrome" described by Ulbright et al. (Am J Med Genet 17:667-668, 1984). This syndrome appears lethal because of the severe renal dysplasia that causes oligohydramnios and pulmonary hypoplasia. Its mode of inheritance seems to be autosomal recessive. PMID- 2240029 TI - Dandy-Walker variant malformation, spastic paraplegia, and mental retardation in two sibs. AB - Two sibs, a boy and a girl, had both hypoplasia of the cerebellar hemispheres and partial agenesis of the cerebellar vermis with normal communication between the fourth ventricle and arachnoid spaces, i.e., the manifestations of the Dandy Walker variant malformation associated with agenesis of the corpus callosum. Both sibs were mentally retarded and had spastic paraplegia. The occurrence of a distinct and similar pattern of congenital anomalies in sibs born to healthy parents points toward a "new" syndrome caused by the homozygous state of an autosomal recessive gene. Prenatal ultrasonographic diagnosis is possible at least for the more severe form of the brain anomalies. PMID- 2240031 TI - Characterization of deletions in the dystrophin gene giving mild phenotypes. AB - We have characterized deletions of the dystrophin gene in patients suffering from relatively mild muscular dystrophy. Our data show that most of the Becker muscular dystrophy (BMD) patients have intragenic deletions which leave the protein reading frame in phase. Remarkably, large deletions of the region corresponding to the central triple helical repeats in the protein can result in an exceptionally mild phenotype. Three brothers suffering from BMD, glycerol kinase deficiency, and adrenal hypoplasia possess a deletion at the 3' end of the gene. They also display developmental delay. Thus the 3' processing of the gene must be necessary for the correct function of the dystrophin molecule. PMID- 2240032 TI - Severe combined immunodeficiency syndrome associated with autosomal recessive familial multiple gastrointestinal atresias: study of a family. AB - Hereditary multiple atresias involving the gastrointestinal tract from pylorus to rectum are the most unusual form of intestinal atresia; the type of inheritance was suggested to be autosomal recessive. The inheritance of the severe combined immunodeficiency syndrome can be autosomal recessive or X-linked. We report on 3 sibs with multiple-level intestinal atresias. One sib had severe combined immunodeficiency syndrome and clinical histories of the other 2 sibs strongly suggested a congenital immunodeficiency syndrome. The parents of those children were healthy and nonconsanguineous. To our knowledge, this is the first report of the association of multiple gastrointestinal atresias and immunodeficiency which appears to have an autosomal recessive pattern of transmission. Our family report suggests that, in the presence of multiple gastrointestinal atresias, attention should be given to possible associated immunological disorders. PMID- 2240033 TI - Carrier testing and prenatal diagnosis for hemophilia: experiences and attitudes of 549 potential and obligate carriers. AB - Experiences with and attitudes toward carrier testing and prenatal diagnosis were evaluated among 549 potential and obligate carriers of hemophilia. Almost everybody considered carrier testing to be useful. Forty-nine percent had been tested for carriership, 10% had only received limited information, and 41% had not been tested and had never received information about the heredity of hemophilia. More married women, women with severe hemophilia in their family, and women closely related to a patient with hemophilia had been tested for carriership than others. Lack of information about the probability of carriership for female relatives and a similar ignorance of the possibility of carrier testing were important reasons for not having been tested. Eleven percent of the women with one or more children had undergone prenatal diagnosis in the past. Thirty-one percent of the study population would favour prenatal diagnosis with the implication of a potential abortion in early pregnancy and half of them would choose this option even in late pregnancy. Most of the women who objected to prenatal diagnosis did so because they did not consider hemophilia to be a sufficiently serious disorder to justify an abortion. PMID- 2240034 TI - Familial sex chromosomal mosaicism. AB - Familial mosaicism has rarely been reported either for autosomes or sex chromosomes. Its recognition poses problems in prognosis, especially in prenatal diagnosis. Three generations of females showed sex chromosomal mosaicism with 3-4 cell lines, the diploid predominant. Phenotypic effect, if any, appeared limited to reduced fertility. The proposita, ascertained prenatally, has grown and developed normally. A dominant gene mechanism most likely accounts for the observations, either autosomal or X-linked. If the mechanism in this family is monogenic, then the gene may not be strictly private considering the frequency of mosaic amniotic fluid cell cultures. PMID- 2240035 TI - Euchromatic 9q + heteromorphism in a family. PMID- 2240036 TI - Anophthalmia in Delleman syndrome. PMID- 2240038 TI - A sibship with Roberts/SC phocomelia syndrome. AB - We report on a family in which 3 sibs have Roberts/SC phocomelia syndrome. One child has survived to age 9 years. The clinical manifestations and the natural history of this syndrome are reviewed. PMID- 2240037 TI - An animal model of the Marfan syndrome. AB - A congenital syndrome of long, thin limbs, severe joint and tendon laxity, microspherophakia, ectopia lentis, heart murmurs and aortic dilatation was identified in 7 calves. All affected calves were sired by a single phenotypically normal bull suspected of germline mosaicism for a new mutation resulting in this disease. One of the calves subsequently died with ruptured aorta at age 16 months. Histopathologic and electron microscopic studies of the aortic media of affected calves demonstrated disorganized elastin and narrowed elastic lamina separated by widened spaces. This bovine disease provides a unique animal model of the human Marfan syndrome. A herd of cattle with this disease is being developed for further studies. PMID- 2240039 TI - Craniosynostosis and lid anomalies: report of a girl with Michels syndrome. AB - We report on a 2-year-old girl with Michels syndrome, a condition characterized by mental deficiency, craniosynostosis, blepharophimosis, ptosis, and epicanthus inversus. The phenotypic findings are compared with those of previously reported cases. PMID- 2240040 TI - Segregation analysis of the X-chromosome in a family with Rett syndrome in two generations. AB - We report on the first family in which Rett syndrome (RTS) appeared in two consecutive generations. The index case is a 12-year-old girl (classical RTS); her maternal aunt, age 44 years, has mild RTS. Clinically, the family illustrates the wide phenotypic variability between cases, particularly in severity of neurological manifestations. We have analyzed the short arm of the X-chromosome of the family with gene technology. This did not uncover any genetic marker for diagnosis, but it did suggest how the syndrome might have segregated in the family. A cytogenetic analysis gave no information about chromosome abnormalities. PMID- 2240041 TI - Familial tetralogy of Fallot and glaucoma. AB - All 3 daughters of a mother with glaucoma had a conotruncal abnormality of the heart and glaucoma. The presence of heart and eye anomaly may be coincidental; however, both may be related to abnormal development of neural crest. The pedigree suggests autosomal dominant inheritance in this family. PMID- 2240042 TI - EEC syndrome: report on 20 new patients, clinical and genetic considerations. AB - We report on 20 Brazilian patients (11 sporadic and 9 familial cases) with the ectrodactyly, ectodermal dysplasia, clefting syndrome (EEC syndrome). Genetic aspects, clinical manifestations, and differential diagnosis of the syndromes involving ectodermal dysplasia/limb anomalies and cleft lip/palate are discussed. PMID- 2240043 TI - Microphthalmos in the presumed homozygous offspring of a first cousin marriage and linkage analysis of a locus in a family with autosomal dominant cerulean congenital cataracts. AB - A family with autosomal dominant congenital cataracts was studied to determine clinical variability. A total of 159 relatives was ascertained; 17 affected and 19 normal individuals were evaluated and their blood sampled for inclusion in the linkage analysis. The disease was compatible with normal to mildly decreased visual acuity until adult life in all affected except the product of a consanguineous marriage of affected first cousins who was born with bilateral microphthalmos and dense congenital cataracts, attributed to homozygosity of the cataract gene. There were no extraocular abnormalities; the patient was of normal intelligence. Twenty-three markers were typed, 18 of which were informative. Linkage could be excluded for all 18 markers at short distances. PMID- 2240044 TI - Unilateral VATER association. AB - We describe a case of unilateral "VATER association." In addition to the VATER manifestations, the patient had hemihypoplasia, unilateral congenital paralysis of a leg, and delayed ossification of the femoral head and carpal bones. All of the manifestations involved the left side of the body. The only drug exposure identified was a Chinese herbal medicine taken by the mother during early pregnancy. PMID- 2240045 TI - De novo (15;21) unbalanced translocation of paternal origin in a girl with Prader Willi syndrome. AB - We describe a 3-month-old girl with Prader-Willi syndrome and a de novo unbalanced karyotype 45,XX,t(15;21)(q13;q22.3). This rearrangement, resulting in monosomy for the pericentromeric region of chromosome 15 and a virtual monosomy for the 21q distal band, had a paternal origin as demonstrated by Q and NOR staining. PMID- 2240046 TI - Syndrome of mental retardation, facial anomalies, hypopituitarism, and distal arthrogryposis in sibs. AB - A brother and a sister presented with a malformation syndrome consisting of facial anomalies, distal arthrogryposis with camptodactyly of fingers and "hammer toes," severe mental retardation, and hypopituitarism. The girl is now 6 1/2 years old and exhibits severe mental retardation. She has abnormal secretion of growth hormone and responded to growth hormone therapy. Her brother was born with the same facial manifestations, distal contractures, and hypopituitarism. He died unexpectedly at age 3 months of no apparent cause. The occurrence of the syndrome in 2 sibs of different sex suggests autosomal recessive inheritance. PMID- 2240048 TI - Ring chromosome 4 in a child with duodenal atresia. AB - We report on a 19-month-old girl with ring chromosome 4 and a multiple congenital anomaly syndrome. The clinical and cytogenetic findings are compared with those of previous cases in whom the breakpoints in ring chromosome 4 are known. PMID- 2240047 TI - Determining the origins and the structural aberrations of small marker chromosomes in two cases of 45,X/46,X, + mar by use of chromosome-specific DNA probes. AB - A 17-year-old girl (S.M.) and a 13-year-old girl (C.L.) both with Ullrich-Turner syndrome (UTS) were found to have 45,X/46,X, + mar mosaicism. The marker chromosomes in both patients were very small in size. In S.M. the marker chromosome was present in 80% of phytohemagglutinin-stimulated lymphocytes, 28% of skin fibroblasts, and 11-20% of gonadal fibroblasts. In C.L., the small marker chromosome was found in 50% of stimulated lymphocytes. S.M. is of normal height, but C.L. is short. Molecular hybridization with a number of Y-specific DNA probes demonstrated their presence in S.M. but absence in C.L. In situ hybridization with Y-specific and X-centromere-specific DNA probes confirmed the Y origin of the marker chromosome in S.M. and the X origin of the minute chromosome in C.L. Biotinylated centromere and telomere probes were also used for in situ hybridization to show the presence of centromeric and telomeric sequences in the Y-marker chromosome, suggesting that the deletion of this marker chromosome is interstitial. PMID- 2240049 TI - Walker-Warburg syndrome with microtia and absent auditory canals. AB - Walker-Warburg syndrome is a lethal, autosomal recessive disorder characterized by anomalies of the central nervous system and eye. Typical findings include hydrocephalus, agyria, retinal dysplasia, cerebellar dysgenesis, anterior chamber dysgenesis, and encephalocele. Recently, the phenotypic spectrum has been expanded to include congenital muscular dystrophy. Two sibs with Walker-Warburg syndrome are reported. One sib had congenital glaucoma and hydrocephalus. The other sib had hydrocephalus, microtia, absent auditory canals, and pale retinas, barely within the phenotypic spectrum of the disorder. Elevation of muscle enzymes was consistent with the diagnosis of Walker-Warburg syndrome. PMID- 2240050 TI - Adjacent-2 disjunction of a maternal t(9;22) leading to duplication 9pter----q22 and deficiency of 22pter----q11.2. AB - The proposita presented at birth with multiple congenital anomalies including craniofacial anomalies, bilateral cleft lip and palate, abnormalities of the urogenital system, talipes equinovarus, and the DiGeorge sequence. Cytogenetic investigation showed a 46,XX,-22,+der(9)t(9;22)(q22;q11.2) karyotype. The mother, maternal uncle, and maternal grandmother of the infant are carriers of a reciprocal balanced translocation involving chromosomes 9 and 22 at regions q22 and q11.2, respectively. The unbalanced karyotype seen in the proposita arose due to an adjacent-2 disjunction of the quadrivalent in the mother. Prenatal diagnosis of the second pregnancy of this woman showed a similar karyotype. Review of the literature shows that adjacent-2 disjunction may occur preferentially when certain chromosomes are involved in translocations. PMID- 2240051 TI - Prevalence study of Prader-Willi syndrome in North Dakota. AB - A prevalence study of Prader-Willi syndrome (PWS) has been conducted in North Dakota. All pediatricians, neurologists, child psychiatrists, psychologists, and clinical geneticists were surveyed. The state's comprehensive evaluation center, the state hospital, the state institution for the mentally retarded, and group homes for the developmentally disabled, including one for persons with PWS, were also contacted. Seventeen patients were identified, 8 males, 8 females, and one patient whose sex was not specified. This suggests a prevalence rate of 1 per 16,062 in North Dakota. PMID- 2240052 TI - Familial IgM mesangial nephropathy: a morphologic and immunogenetic study of three pedigrees. AB - Eight patients belonging to 3 unrelated families had biopsy-proven IgM mesangial nephropathy. In the first family, the mother and the 2 daughters were affected; in the second, the mother and the son; in the third, 2 sisters and the brother. Two additional sisters of the third family showed a clinical picture consistent with chronic glomerulonephritis. The clinical picture was that of hematuria and/or proteinuria. No patients had nephrotic syndrome. Genealogic investigation enabled us to discover 2 additional affected members in the kindred of the first family (1 with IgA nephropathy, 1 with clinical glomerulonephritis) and 3 other affected members in the pedigree of the third family (1 with IgA nephropathy, 1 with sclerosing glomerulonephritis, 1 with clinical glomerulonephritis). Immunogenetic studies showed the recurrence of an extended haplotype bearing DR beta 11-DQ beta 3B-DQ alpha 2-C4A3-C4B1-BfS in 9 of 10 affected members. Our data suggest that genetic factors may be involved in the mechanism of the disease and support the hypothesis that IgM nephropathy is a distinct disease entity. PMID- 2240053 TI - Lysine vasopressin in the treatment of refractory hemodialysis-induced hypotension. AB - The etiology of hemodialysis-induced hypotension is multifactorial. We assessed the efficacy of intranasal lysine vasopressin (LV) in 6 patients with refractory hemodialysis-induced hypotension. Autonomic testing was abnormal in all. Intranasal LV and placebo were assessed in a double-blind crossover fashion. With LV, the mean number of hypotensive episodes was less (0.9 +/- 0.8 vs. 1.5 +/- 1; t = 3.95, p less than 0.05), as was the total volume of intravenous fluid administered because of hypotension (155 +/- 57 vs. 280 +/- 123 cm3; t = 2.98, p less than 0.05). Systolic, diastolic, and mean arterial blood pressures were significantly greater at 90 min of the dialysis session. Measured baseline epinephrine, norepinephrine, and antidiuretic hormone levels were elevated above normal levels and fell with hypotension despite the use of LV. The results from this study demonstrate the utility of LV in the treatment of refractory hemodialysis-induced hypotension. PMID- 2240055 TI - End-stage renal disease in systemic amyloidosis: clinical course and outcome on dialysis. AB - We studied a group of 48 patients with systemic amyloidosis and end-stage renal disease (ESRD) treated with chronic dialysis to analyze the clinical course and the factors which can influence survival. This group was compared to a control group of 63 nondiabetic patients without amyloidosis with ESRD treated with hemodialysis. The median survival of the experimental group was 52 months; 1-, 2- and 6-year actuarial survival was 72, 62, and 44%, while in the control group it was 95, 91, and 81%, respectively (p less than 0.001). Survival was significantly shorter for patients with amyloidosis who rapidly (less than 3 months) progressed to ESRD or who had an acute deterioration in renal function immediately prior to the need for dialysis. The median survival in these cases was 4 and 1.5 months, respectively. Age, the presence or the degree of renal failure at the moment of diagnosis, and the type of amyloidosis did not affect the survival of these patients. Despite a shorter period of time spent on dialysis, these patients had a similar number of hospital admissions, cardiovascular and infectious events as the control patients, but more gastrointestinal disorders (bleeding and chronic diarrhea) and blood access problems. In conclusion, amyloidotic patients maintained on chronic dialysis have high morbidity and mortality rates. Nevertheless, acceptable survival is predictable in stable patients who progress slowly to ESRD. PMID- 2240054 TI - Normal T lymphocyte function in patients with end-stage renal disease hemodialyzed with 'high-flux' polysulfone membranes. AB - T lymphocyte function was analyzed in patients hemodialyzed with 'high-flux' polysulfone membranes, which have been reported to improve the patients' overall clinical condition and well-being. For comparison purposes, patients treated by the use of 'low-flux' cuprophane membranes were also studied. Peripheral blood white cell counts, numbers of lymphocytes as well as the numbers of T cells and their CD4 and CD8 subsets were within normal range in both patient groups. The absolute number of B cells was slightly decreased in cuprophane-membrane- but not polysulfone-membrane-treated patients. The proliferative response of T lymphocytes after stimulation with optimal concentration of phytohemagglutinin (PHA) was normal in patients treated with 'high-flux' membrane dialysis but significantly reduced in those treated with cuprophane membranes. The generation of interleukin-2 (IL-2) receptor on T lymphocytes after PHA stimulation was normal in the polysulfone-membrane-treated group and slightly impaired in the cuprophane-membrane-dialyzed patients. Production of both IL-2 and interleukin-1, as well as the natural killer cell activity, in patients treated by 'high-flux' membrane dialysis were also comparable to controls. The levels of serum beta 2 microglobulin were significantly elevated in patients-maintained on 'high-flux' dialysis membranes but did not reach the levels seen in patients dialyzed by cuprophane membranes. The beta 2-microglobulin at levels seen in patients on cuprophane dialysis had no effects on activation and proliferation of control lymphocytes in vitro. These results suggest that impaired functional responses of T lymphocytes seen in end-stage disease patients on prolonged hemodialysis with cuprophane membranes are not seen in similar patients hemodialyzed with polysulfone membranes. PMID- 2240056 TI - Development of hypertension in IgA nephropathy as a marker of a poor prognosis. AB - We have studied 209 patients with IgA nephropathy. 26 were hypertensive at the time of renal biopsy, and 59 patients developed hypertension during follow-up. Survival statistics show that only 45% of the patients will remain normotensive 10 years after renal biopsy. The presence of hypertension at renal biopsy correlated well with the usual parameters of a poor prognosis. The same markers predicted a later development of hypertension in patients who were normotensive at the time of renal biopsy. When hypertension is established, the prognosis is poor. Three years after diagnosis of hypertension, the renal survival was found to be 70% in the 59 patients we have followed. It is also possible that the markers of a poor prognosis actually predict the progression rate rather than the prognosis, because in time, some patients with initially mild manifestations of the disease will progress to end-stage renal failure. PMID- 2240057 TI - The spectrum of ciclosporin nephrotoxicity. PMID- 2240058 TI - Caffeine potentiates the nephrotoxicity of mefenamic acid on the rat renal papilla. AB - The effect of caffeine given in combination with mefenamic acid on the renal papilla was studied. Sprague-Dawley rats were divided into four groups and gavage fed either control suspension, mefenamic acid, mefenamic acid and caffeine or caffeine alone for 4 months. Semiquantitative urinalysis was performed at 3 months and showed increased haematuria in the mefenamic acid and caffeine group. There were no significant differences in serum creatinine at sacrifice. Renal histology revealed more advanced papillary necrosis in rats gavage fed mefenamic acid and caffeine compared with all other groups (p less than 0.0001). Rats fed mefenamic acid alone showed more damage than control and caffeine-fed groups (p less than 0.0001, p less than 0.0002, respectively). This suggests that caffeine potentiates the nephrotoxicity of the non-steroidal anti-inflammatory drug, mefenamic acid, on the rat renal papilla. The mechanism of this potentiation by caffeine is yet to be defined. PMID- 2240059 TI - A role for adenosine calcium and ischemia in radiocontrast-induced intrarenal vasoconstriction. AB - These studies were designed to test the hypothesis that adenosine and calcium are important in mediating radiocontrast-media-associated reduction in renal blood flow (RBF) in the dog. Intravenous verapamil (V) and diltiazem (DTZ) infusion significantly attenuated the magnitude of the vasoconstrictor response observed after each intrarenal contrast media (CM) injection. (First injection: -47 +/- 8% control vs. -14 +/- 3% V, p less than 0.03; -38 +/- 4% control vs. -19 +/- 3% DTZ, p less than 0.02. Second injection: -33 +/- 6% control vs. -12 +/- 1% V, p less than 0.03; -32 +/- 5% control vs. -17 +/- 2% DTZ, p less than 0.03. Third injection: -32 +/- 6% control vs. -11 +/- 5% V, p less than 0.03; -38 +/- 5% control vs. -10 +/- 5% DTZ, p less than 0.02). Furthermore, V and DTZ almost completely abolished the increase in renal vascular resistance (RVR) induced by each CM administration. Theophylline also significantly attenuated the magnitude of the vasoconstrictor response observed after CM injection (first injection: -31 +/- 3% control vs. -12 +/- 3% theophylline, p less than 0.05; second injection: 26 +/- 3% control vs. -12 +/- 3% theophylline, p less than 0.03). Similarly, theophylline blunted the increase in RVR induced by CM injection. In addition, theophylline inhibited exogenous adenosine-induced decrease in RBF (-61 +/- 10% and -26 +/- 1% decrease in RBF without and with theophylline, respectively). In contrast, dipyridamole significantly enhanced the vasoconstriction induced by CM (first injection: 25 +/- 3% control vs. 49 +/- 4% dipyridamole; second injection: 31 +/- 3% control vs. 48 +/- 4% dipyridamole p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240061 TI - Unusual case of crescentic glomerulonephritis associated with malignant lymphoma. A case report and review of the literature. AB - Renal lesions in non-Hodgkin's lymphoma are rare. Furthermore, to the best of our knowledge, only 5 cases of crescentic glomerulonephritis associated with non Hodgkin's lymphoma have been previously described. We report a case of crescentic glomerulonephritis and renal failure which preceded the diagnosis of non Hodgkin's lymphoma. Following steroid therapy there was a resolution of these histological findings a year later. PMID- 2240060 TI - Membranous nephropathy associated with giant lymph node hyperplasia. A case report with histological and ultrastructural studies. AB - A young woman presented with nephrotic syndrome due to membranous nephropathy and a localized form of giant lymph node hyperplasia (Castleman's disease) occurring as a large intra-abdominal mass. Five months after surgical removal of the mass, only mild proteinuria persisted. Twenty months later a second kidney biopsy showed a near-normal morphology. Six years later the patient was free of symptoms and had normal urinalysis. Reviewing the pertinent literature, it seems to be the first case of a biopsy-proven cure of membranous nephropathy in a patient with membranous nephropathy and Castleman's disease. PMID- 2240062 TI - Nonamyloidotic fibrillar glomerulopathy and recurrent gestational anasarca. AB - Congo-red-negative microfibrils have been described in various glomerular diseases, some of which have no known etiology. We report the unusual case of a young woman who, over a period of 17 years, developed recurrent gestational anasarca but was asymptomatic between pregnancies except for proteinuria. Her blood pressure and renal function have remained normal over the years. A renal biopsy done 5 years after her third pregnancy showed diffuse mesangial expansion and irregular thickening of the glomerular basement membrane, both caused by the deposition of nonamyloidotic microfibrils. We discuss the differential diagnosis of this case and review the pertinent literature. PMID- 2240063 TI - Control of renovascular hypertension by renal embolization. AB - Two cases with medically well-controlled renovascular hypertension due to unilateral contracted kidney were treated by percutaneous renal embolization. One of the patients had two aneurysms of the renal artery in addition to the stenosis. Both patients remained normotensive without medication after follow-ups of 6 and 24 months, respectively. PMID- 2240064 TI - Primary oxalosis mimicking hyperparathyroidism diagnosed after long-term hemodialysis. AB - Primary oxalosis is a rare inborn error of oxalate metabolism. Most cases are discovered in children, but occasionally symptoms begin later in life. Since early deaths in the past were from renal failure, prolonged survival obtained with chronic dialysis allows oxalosis to develop. This paper presents a 38-year old man with an atypical history of type-I primary hyperoxaluria, not diagnosed until after 5 years of dialysis. Bone biopsy was performed because the biochemical and radiologic features did not seem consistent with a putative diagnosis of secondary hyperparathyroidism. This case emphasizes the clinical heterogeneity of this disorder, and the need for its considerations in the spectrum of dialysis-related bone diseases. It also stresses that bone oxalosis may mimic hyperparathyroidism, especially radiologically. Differential diagnosis is therefore mandatory. PMID- 2240065 TI - Adenoviral acute hemorrhagic cystitis following renal transplantation. PMID- 2240066 TI - Replanted pride in nursing. PMID- 2240067 TI - Are you a worrier? PMID- 2240068 TI - A nursing nightmare--or was it? PMID- 2240069 TI - Men in nursing. PMID- 2240070 TI - Early-stage breast cancer: the options. PMID- 2240071 TI - Early-stage breast cancer: how nurses help. PMID- 2240072 TI - Early-stage breast cancer: adjuvant drug therapy. PMID- 2240073 TI - AIDS: light at the end of a decade. PMID- 2240074 TI - Emergency! It's cyanide! PMID- 2240075 TI - What's right about grievances? PMID- 2240076 TI - How do you manage extraventricular drainage? PMID- 2240077 TI - Southwest job focus: spirit of the Southwest: action in the 90's. PMID- 2240078 TI - Doin' the oyster check. PMID- 2240079 TI - Arizona job focus. More than a pretty place. PMID- 2240080 TI - IRS challenges the "independent contracting" option for nurses. PMID- 2240081 TI - Human oocyte and preembryo donation: an evolving method for the treatment of infertility. AB - The utilization of oocyte and preembryo donation in the treatment of infertility has recently expanded. Since 1983, modifications in the retrieval of donated female gametes have enhanced both the safety and the efficacy of the procedure. Pregnancy rates in women receiving donated preembryos are remarkably high, with success occurring in 25% to 50% of transfer cycles. The technology used for preembryo donation continues to evolve, and the current and future role ovum donation in the treatment of infertility. PMID- 2240082 TI - Does obstetric ethics have any role in the obstetrician's response to the abortion controversy? AB - We defend the view that the obstetrician's response to the abortion controversy cannot be based on accounts of the independent moral status of the fetus, because all such accounts are irresolvably disputable. That response, however, can be based on an account of the dependent moral status of the fetus. For such an account the central question is, "When is the fetus a patient?" Viable fetuses are patients. Nonviable third-trimester fetuses are not patients. Previable fetuses are patients solely as a function of the woman's autonomous decision to confer such status. The abortion of a viable fetus is, with few exceptions, never ethically justified, because it is a patient. The abortion of nonviable third trimester fetuses (i.e., premature termination of pregnancy) is justified when the pregnant women consents to it. Abortion of the previable fetus is justifiable when the pregnant women consents to it. We distinguish between professional and private conscience. We identify the limits of the former and the legitimate role of the latter, especially in the area of religious beliefs. Finally, we address the implications of our view for residency training programs. The most important of these implications is that requiring all residents to perform abortions is ethically unjustifiable. PMID- 2240083 TI - Interleukin-1 beta, human leukocyte antigen HLA-DR alpha, and transforming growth factor-beta expression in endometrium, placenta, and placental membranes. AB - Maternal immune recognition of the fetal semiallograft appears to be necessary and beneficial for fetal survival and growth. Interleukin-1 beta and human leukocyte antigen HLA-DR are important for foreign antigen recognition by the immune system, whereas transforming growth factor-beta inhibits many of the immunostimulatory properties of interleukin-1 beta. In this study we found that first-trimester decidua and term placental membranes expressed significantly higher levels of interleukin-1 beta, interleukin-1 beta messenger ribonucleic acid, and human leukocyte antigen HLA-DR alpha messenger ribonucleic acid expression. All tissues found at the maternal-fetal interface, including first trimester decidua, placenta, and placental membranes, contained transforming growth factor-beta and expressed transforming growth factor-beta 1 messenger ribonucleic acid. On the basis of these findings, we suggest that the increase in decidual interleukin-1 beta and human leukocyte antigen HLA-DR alpha during pregnancy may be involved in maternal recognition of the fetal semiallograft and that transforming growth factor-beta production may regulate the local maternal immune response and prevent rejection of the fetus. PMID- 2240085 TI - Immunocytochemical distribution and localization of 15-hydroxyprostaglandin dehydrogenase in human fetal membranes, decidua, and placenta. AB - Biochemical studies have shown the presence of type I oxidized nicotinamide adenine dinucleotide-dependent 15-hydroxyprostaglandin dehydrogenase in human fetal membranes, decidua, and placenta. However, the localization of prostaglandin dehydrogenase within these tissues is not known. Because the distribution of prostaglandin dehydrogenase may affect the concentration of prostaglandins that reach the myometrium, we used immunocytochemistry to localize immunoreactive prostaglandin dehydrogenase in fetal membranes and placenta. We also examined whether this distribution changed with labor. Tissues were collected at term elective cesarean section or after term spontaneous labor and delivery, were fixed, embeded, and sectioned at 5 microns. Immunoreactive prostaglandin dehydrogenase was determined with a polyclonal primary antibody to human placental prostaglandin dehydrogenase and visualized with the avidin-biotin procedure. Epithelial and epithelium-derived cells were identified by positive staining with a polyclonal antikeratin primary antibody. Cytokeratin staining was observed in amniotic epithelium, trophoblast layer of chorion, invading trophoblast in decidua, and all subsets of trophoblast in the placenta. Immunoreactive prostaglandin dehydrogenase was localized to the trophoblast layer of chorion, invading trophoblast in decidua, and in syncytiotrophoblast and intermediate trophoblast but not cytotrophoblast in the placenta. In chorion, approximately 50% to 60% of the nonvacuolated trophoblast cells stained positively for prostaglandin dehydrogenase. There was no change in the localization of immunoreactive prostaglandin dehydrogenase in any tissue in association with labor. PMID- 2240084 TI - Prevalence and determinants of estrogen replacement therapy in elderly women. AB - To better understand which women use estrogen replacement therapy, we examined the prevalence and determinants of estrogen replacement therapy in 9704 nonblack women, age greater than or equal to 65 years, who participated in the multicenter prospective Study of Osteoporotic Fractures. Overall, 13.7% of women reported current use of oral estrogen; 10.9% took estrogen alone and 2.8% took estrogen opposed by progestin. Four percent currently used parenteral estrogen compounds. Current use declined sharply with age from 17% at age 65 to 4% at age greater than or equal to 85. The primary determinant of estrogen replacement therapy was the type of menopause; the odds of using estrogen replacement therapy in current users compared with never users were approximately five times higher in women with a surgical menopause. Estrogen use was more common among women who had higher levels of education and were less obese. Furthermore, estrogen replacement therapy users were more likely to drink alcohol and to participate in sports and recreation. A diagnosis of osteoporosis was the major determinant of continued estrogen use, but only 24% of women with a diagnosis of osteoporosis used estrogen replacement therapy. We conclude that only a small proportion of elderly women in the United States use estrogen replacement therapy. Selection factors for use of estrogen are evident and may introduce bias in studies of estrogen and disease. In consideration of the distribution of these selection factors, estrogen users will tend to be at lower risk of coronary disease and possibly breast cancer but at greater risk for hip fractures. PMID- 2240086 TI - The effect of physical activity during pregnancy on preterm delivery and birth weight. AB - The relationship between physical activity during pregnancy, preterm birth, and gestational age-adjusted birth weight was investigated prospectively in a cohort of 7101 women. This study is one of few to evaluate both employment- and non employment-related physical activity. Prolonged periods of standing were associated with a modestly increased risk of preterm delivery (adjusted odds ratio for greater than or equal to 8 hours/day of standing = 1.31). Heavy work or exercise was not associated with preterm delivery (adjusted odds ratio for greater than or equal to 4 hours per day of heavy work = 1.04). The proportion of infants born preterm did not differ among women working in predominantly standing, active, and sedentary occupations. Physical activity was not associated with gestational age-adjusted birth weight after controlling for confounding variables. These data suggest that unmeasured socioeconomic differences among women reporting different levels of activity may account for previously described associations between physical activity and pregnancy outcome. Most pregnant women who report increased levels of physical activity are not at increased risk of preterm delivery or reduced intrauterine growth. However, these data do not address the role of activity restriction in the management of selected women at high risk for adverse pregnancy outcome. PMID- 2240087 TI - Prenatal diagnosis of laryngeal atresia. AB - In a patient in whom preeclampsia developed at 23 weeks' gestation, ultrasonographic examination of the fetus showed enlarged edematous lungs, a compressed fetal heart, severe ascites, fetal hydrops, and placental edema. Autopsy of the hydropic stillborn infant showed laryngeal atresia. The ultrasonographic appearance of this rare malformation is presented. PMID- 2240088 TI - Correlations between antepartum maternal metabolism and newborn behavior. AB - We suggested that antepartum maternal metabolism may affect later cognitive and behavioral function of progeny by impacting on developing brain cells in utero. This study reports on the observed relationships between serial characterizations of maternal fuels during pregnancy and Brazelton neonatal behavioral assessment scale ratings of offspring from 73 well-controlled pregestational diabetic patients, 112 gestational diabetic patients, and 24 nondiabetic patients. After controlling for the effects of premature birth on the Brazelton neonatal behavioral assessment scale, significant correlations were found between second- and third-trimester glycemic regulation (hemoglobin A1c and fasting plasma glucose levels) and three of four newborn behavioral dimensions of the Brazelton neonatal behavioral assessment scale. In each case, as maternal glucose increased, the newborns' Brazelton neonatal behavioral assessment scale responses were poor. Results were not substantially different when gestational and pregestational diabetic patients were analyzed separately, nor can they be attributed to various perinatal events (neonatal asphyxia, hypoglycemia) or differences in socioeconomic status or ethnicity. The presence of fuel-related neurobehavioral deficits in neonates of diabetic mothers suggests that such infants start their interactions with care givers from a modified base. PMID- 2240089 TI - Antenatal microbiologic and maternal risk factors associated with prematurity. AB - In a prospective study of 202 women (gestational age 24 +/- 4 weeks), we evaluated possible influences of lower genital tract infection or bacterial conditions on obstetric outcomes, including preterm labor, preterm premature rupture of membranes, and preterm birth. The presence of bacterial vaginosis (18.7%) was associated with an increased risk of preterm labor (relative risk, 2.6; 95% confidence interval, 1.08 to 6.46). For women with bacterial vaginosis who also had Mobiluncus species morphotypes identified on Gram stain, the relative risk of preterm labor was 3.8 (95% confidence interval, 1.32 to 11.5). Presence of vaginal Mycoplasma hominis (10.8% of patients) was associated with both preterm labor (relative risk, 1.8; 95% confidence interval, 0.77 to 4.4) and preterm birth (relative risk, 5.1; 95% confidence interval, 1.45 to 17.9). Recovery of Staphylococcus aureus (3.0%) was associated with preterm labor (relative risk, 3.1; 95% confidence interval 1.12 to 8.7). Identification of two or more bacterial-linked abnormalities was also associated with preterm labor (relative risk, 3.3; 95% confidence interval, 1.44 to 7.58). An increased level of vaginal wash protease (greater than or equal to 10 trypsin units) (16%) was associated with preterm labor and was noted in 50% of women with preterm premature rupture of membranes. A history of prior preterm birth was the single best historical predictor of both preterm labor (relative risk, 3.6; 95% confidence interval, 1.92 to 6.83) and preterm birth (relative risk, 6.7; 95% confidence interval, 2.2 to 20.4). History of three or more abortions, antenatal urinary tract infection, and occurrence of medical complications during pregnancy also correlated with increased risk of preterm labor. These findings affirm and refine associations of various maternal reproductive tract infections with preterm labor, premature rupture of membranes, and birth, allowing for controlled treatment trials aimed at prevention of preterm birth. PMID- 2240090 TI - The relationship between plasma estradiol and the increase in bone density in postmenopausal women after treatment with subcutaneous hormone implants. AB - Twenty-three postmenopausal women with a median of 2 years past menopause (range, 1 to 12 years) and a median age of 52 years (range, 39 to 62 years) were recruited to participate in a longitudinal study designed to investigate the factors that influence the increase in bone density with subcutaneous estradiol and testosterone implants. All women received 75 mg of estradiol with 100 mg testosterone subcutaneously. Bone density was measured at the spine and hip by dual-photon absorptiometry before therapy and after 1 year of subcutaneous hormonal therapy. The mean pretreatment bone density at the lumber vertebrae and neck of the femur was 0.84 grams of hydroxyapatite per square centimeter (SD, 0.11) and 0.73 grams of hydroxyapatite per square centimeter (SD, 0.10), respectively. The bone density at both sites increased with values of 0.91 grams of hydroxyapatite per square centimeter (SD, 0.11) and 0.75 grams of hydroxyapatite per square centimeter (SD, 0.11), respectively. These values represent an increase of 8.3% (p less than 0.0001) at the spine and 2.8% (p less than 0.01) at the neck of the femur. The plasma estradiol level increased from a median of 80.5 pmol/L to 453 pmol/L (p less than 0.001). The percentage increase of vertebral bone density was not related to age, number of years past the menopause, pretreatment bone density, or serum testosterone levels, but a significant correlation was found between the percentage increase in bone density at the spine and the serum estradiol level (p less than 0.02, r = 0.45). PMID- 2240091 TI - Fetal eye movement assessed with real-time ultrasonography: are there rapid and slow eye movements? AB - The goal of this study was to determine whether rapid eye movement and slow eye movement exist during the eye-movement period in the human fetus in utero. We studied 21 fetuses with real-time ultrasonography, 10 from 33 to 36 weeks and 11 from 37 to 41 weeks' gestation. We used the duration of eye-movement unit as a parameter and calculated the cumulative duration from the shortest to a given duration of eye movement per individual case. A scattergram of cumulative duration versus given duration obtained from all cases in each age group was analyzed with piecewise linear regression to search for a critical point(s). Critical given duration points were noted and reached statistical significance at 0.62 second and at 0.76 second during 33 to 36 and 37 to 40 weeks of gestation, respectively. These findings reveal two different types of eye movement: one with a duration of less than 0.6 to 0.8 second and the other with a duration of greater than 0.6 to 0.8 second. These findings are compatible with previous criteria on rapid and slow eye movements, respectively, at 33 weeks of gestation onward. The mean value of cumulative duration at the critical point increased from 29.0% between 33 and 36 weeks to 47.1% between 37 and 41 weeks of gestation, indicating an increase in the proportionate amount of time maintaining rapid eye movement as gestation advances. PMID- 2240092 TI - Continuous or interrupted fascial closure: a prospective evaluation of No. 1 Maxon suture in 402 gynecologic procedures. AB - During a 14-month period of using a long-term absorbable suture (No. 1 Maxon), 402 patients were entered into a prospective, randomized trial of fascial closure. Patients were randomized between a continuous closure (201 patients) and an interrupted en bloc (201 patients) technique. Each patient was subjected to a preoperative and intraoperative protocol for wound management. There were no acute wound failures. Wound infection rates and risk of hernia were not apparently affected by closure technique. PMID- 2240093 TI - Endometrioma of the liver. AB - Hepatic endometriosis is extremely rare. We describe a patient sent to us with epigastric pain as the only symptom and who was found to have associated endometrioma of the liver and left ovary. We suggest a gynecologic evaluation before surgery for hepatic cyst of unknown cause. PMID- 2240094 TI - Antinuclear antibodies in sera of patients with recurrent pregnancy wastage. AB - Four groups of women were studied to determine whether low-level antinuclear antibody titers are associated with a higher risk for pregnancy loss. Group A consisted of 30 patients with a history of unexplained fetal losses. Group B consisted of 30 women with "explained" fetal losses (e.g., uterine septum or luteal phase defect). Ages and number of losses were comparable between the women in groups A and B. Group C consisted of 61 healthy pregnant women. Group D involved 61 healthy nonpregnant women of reproductive age. In groups A and B, 40% and 53.3% of the respective patients had antinuclear antibody titers greater than or equal to 1:40. In groups C and D the frequencies of positive antinuclear antibody titers were 8.2% and 5.6%, respectively. This study demonstrates a high prevalence of low-titer antinuclear antibody-positive serum in patients with explained and unexplained pregnancy losses. PMID- 2240096 TI - Hemoperitoneum as a result of coital injury without associated vaginal injury. AB - Hemoperitoneum as a result of coital injury without associated vaginal injury is an extremely rare entity, and evidence by only five cases that have been reported in the medical literature to date. We report five additional cases encountered in two medical centers. Two of these were ruptured corpus luteum cysts, one was a laceration of the round ligament, another was a laceration of an ovary, and the fifth was rupture of a serous cystadenoma. This diagnosis should be considered in patients with hemoperitoneum after coitus. PMID- 2240095 TI - Corpus luteum function in early pregnancies is primarily determined by the rate of change of human chorionic gonadotropin levels. AB - Regulation of human corpus luteum activity was studied with radioimmunoassays and bioassays of sera drawn serially from women suspected of having ectopic pregnancies. Progesterone values exhibited considerable overlap in pregnancies that were subsequently classified as normal intrauterine (n = 21), ectopic (n = 35), or spontaneous abortion (n = 14). The rate of change of human chorionic gonadotropin concentration was significantly correlated with progesterone levels in ectopic (r = 0.64) and all pregnancies (r = 0.70). There was no correlation (r = -0.18) between the rate of change of human chorionic gonadotropin and the bioactivity produced per volume of serum. Ectopic pregnancies and normal intrauterine pregnancies did not differ in their ratio of in vivo bioactivity to immunoactivity. From these data we conclude that corpus luteum activity is primarily regulated by the rate of change of human chorionic gonadotropin concentration, without the involvement of other serum factors. We also conclude that reduced corpus luteum function in ectopic pregnancies is not a result of biochemical modification of the human chorionic gonadotropin molecule. Finally, we discourage the use of single progesterone values in screening for ectopic pregnancies because of the considerable overlap in progesterone values among these and normal intrauterine pregnancies. PMID- 2240097 TI - Postmortem chorionic villus sampling is a better method for cytogenetic evaluation of early fetal loss than culture of abortus material. AB - In utero chorionic villus sampling at the time of diagnosis of intrauterine fetal death is compared with more traditional use of cultured fetal skin, products of conception, or amniocentesis. A total of 102 specimens from early fetal losses were evaluated for success in karyotyping and chromosomal results. We found postmortem chorionic villus sampling is technically possible, offers the highest likelihood of getting a cytogenetic result, and is a rapid, reliable, and safe technique. The extraembryonic component of intrauterine fetal deaths appears to remain viable and continues to grow long after the embryo has died. Samples obtained at the time of diagnosis of fetal death offer the greatest changes of successfully obtaining a karyotype. The incidence of chromosome abnormalities associated with fetal loss, particularly trisomies, is higher than previous data suggested. PMID- 2240098 TI - Detection of congenital toxoplasmosis by chorionic villus sampling and early amniocentesis. AB - We describe a strategy used in this case to detect congenital toxoplasmosis early in pregnancy. Combination of chorionic villus sampling and early amniocentesis with an in vitro cell culture technique makes prenatal diagnosis of congenital toxoplasmosis possible from the end of the first trimester of pregnancy. PMID- 2240099 TI - The "stuck twin" phenomenon: ultrasonographic findings, pregnancy outcome, and management with serial amniocenteses. AB - Thirteen consecutive twin pregnancies affected by the "stuck twin" phenomenon were reviewed to determine the potential benefit of serial amniocenteses. The fetal survival rate for the eight pregnancies that underwent serial amniocenteses was 69% (11 of 16 fetuses). This is significantly improved compared with a fetal survival rate of 20% among the five preceding pregnancies managed without serial amniocenteses at the same institution (p = 0.01). It is also markedly improved compared with a combined fetal survival rate of 16% among 48 previously reported pregnancies with the stuck twin phenomenon managed without serial amniocenteses (p less than 0.0001). Survival correlated with the absence of concomitant pregnancy complications (i.e., maternal hypertension or intractable labor) and with the absence of severe fetal structural abnormalities. Procedural complications occurred in three of eight pregnancies (37.5%) managed with serial amniocenteses and was attributed as a cause of fetal death in one case. Two of 11 survivors (18%) had complications after serial amniocenteses including brain infarction and renal tubular necrosis. Serial amniocenteses may significantly improve the survival rate of twin gestations affected by the stuck twin phenomenon but may be associated with complications among survivors. PMID- 2240100 TI - Twin-twin transfusion syndrome. AB - Twin-twin transfusion syndrome associated with acute polyhydramnios in one sac and severe oligohydramnios in the other, which characteristically is diagnosed between 18 and 28 weeks, is associated with a high mortality rate for the involved twins. Patients who are managed without intervention have essentially 100% perinatal mortality. Nineteen patients with this diagnosis were treated at Good Samaritan Medical Center over a 5-year period. Because of the known perinatal mortality and because of early experiences with the twin-twin transfusion syndrome, we began to actively intervene in such patients with various modes of therapy. As experience was gained, it was found that repeated therapeutic amniocenteses, if performed before severe maternal abdominal distention or labor, appears to be beneficial. PMID- 2240101 TI - Pregnancy in a patient with treated Wilson's disease: a case report. AB - Pregnancy should have a successful outcome in a patient with treated Wilson's disease if complications are excluded before conception. Chelating treatment must be maintained, although there is some concern about its teratogenicity. We describe the course of pregnancy in a patient followed up in our department. PMID- 2240102 TI - Nature of gonadotropin-releasing hormone self-priming of luteinizing hormone secretion during the normal menstrual cycle. AB - To investigate further the nature of the gonadotropin-releasing hormone self priming effect on luteinizing hormone release, we administered two submaximal doses of gonadotropin-releasing hormone 2 hours apart to women at three stages of the menstrual cycle and analyzed the resultant luteinizing hormone secretory episodes with deconvolution analysis. When the characteristics of the secretory episodes associated with the second gonadotropin-releasing hormone challenge were compared with those associated with the first, both an enhanced maximal secretory rate and mass of luteinizing hormone secreted was demonstrable at each phase of the cycle. No differences in the luteinizing hormone secretory event half duration were detected when the responses to the first and second gonadotropin releasing hormone doses were compared. These data confirm the gonadal hormone milieu-associated self-priming effect of gonadotropin-releasing hormone on luteinizing hormone release and indicate that it is the rate with which luteinizing hormone molecules are discharged from the pituitary gland, rather than the duration of the secretory episode itself, that provides for the self priming effect. PMID- 2240103 TI - The perinatal impact of cocaine, amphetamine, and opiate use detected by universal intrapartum screening. AB - Universal urine testing for cocaine, amphetamines, and opiates was performed on 1643 women admitted to an obstetric service for a 1-year period with 20.5% having positive results. There were 299 patients with positive toxicology results matched for race and discharge date with patients having negative toxicology and drug history. Significant differences in age, prior obstetric history, prenatal care, alcohol history, and smoking were noted between groups. There was a significant decrease in birth weight, head circumference, length, and gestational age for the drug-positive group, which was most marked in cocaine and multiple drug users. These differences persisted after we controlled for smoking, prenatal care, and prior preterm births. Differences in birth weight and head circumference remained after we controlled for gestational age. Rates of congenital anomalies and abruptio placental were similar between groups. Perinatal substance abuse is independently associated with growth retardation and prematurity. Multiple risk factors are frequently present, necessitating a comprehensive approach to prenatal care. PMID- 2240104 TI - Inhibition of aromatase activity by 8-bromo-cyclic adenosine monophosphate in cultured first-trimester human trophoblast. AB - We have previously shown that 8-bromo-adenosine-3':5'-cyclic monophosphate inhibits production of estradiol from androgen precursors in trophoblast isolated from term placentas. In these experiments we sought to evaluate the effect of 8 bromo-adenosine-3':5'-cyclic monophosphate on aromatase activity in first trimester trophoblast culture. Trophoblast cells were enzyme dispersed from first trimester placentas and purified on a Percoll gradient. On the third and fourth day after dispersion cultures were treated with androstenedione or testosterone with and without 2 mmol/L 8-bromo-adenosine-3':5'-cyclic monophosphate. The quantity of estradiol, estrone, progesterone, human placental lactogen, and human chorionic gonadotropin was determined by radioimmunoassay. We concluded that in first-trimester trophoblast, as previously reported in term trophoblast, 8-bromo adenosine-3':5'-cyclic monophosphate inhibited the production of estradiol from the supplied androgen precursors. Human chorionic gonadotropin and human placental lactogen production was stimulated by 8-bromo-adenosine-3':5'-cyclic monophosphate. Progesterone production was either stimulated or was unchanged by the presence of 8-bromo-adenosine-3':5'-cyclic monophosphate. PMID- 2240105 TI - A reappraisal of the need for autologous blood donation in the obstetric patient. AB - There has been recent interest in autologous blood donation in obstetric patients, but little attention has been paid to whether such programs are needed or whether the patients that will require transfusion can be accurately predicted. At the University of California San Diego Medical Center from July 1 to Dec. 31, 1988, there were 2265 deliveries; 13 women (0.57%) received blood transfusions. Traditionally accepted risk factors were identified in 251 patients, with only four (1.6%) requiring transfusion. Among the 150 patients delivered by repeat cesarean section, only one (0.7%) required blood. one of 27 (3.7%) multiple gestations, two of eight (25%) patients with placenta previa, and none of the 66 grandmultiparous women had transfusions. These data suggest that autologous blood donation may not be beneficial or cost effective when the low frequency of blood transfusions in this high-risk obstetric population and the difficulty in accurately predicting those likely to require transfusions are considered. PMID- 2240106 TI - Direct ultrasonographic measurement of fetal lung length in normal pregnancies and pregnancies complicated by prolonged rupture of membranes. AB - Fetal lung length was measured directly with ultrasonography in 20 patients with prolonged rupture of membranes, commencing before 25 weeks' gestation. Measurements were made weekly and compared with data collected from 310 normal pregnancies. Measurement of fetal lung length by ultrasonography was a good predictor of pulmonary hypoplasia, predicting greater than 90% of cases. There was a good correlation between lung size assessed by the last ultrasonographic examination and lung weight postmortem (r = 0.783, p less than 0.05). Lung length measurements were superior to fetal chest circumference measurements in the identification of pulmonary hypoplasia. There was a significant negative association between the amount of amniotic fluid and pulmonary hypoplasia (p less than 0.05). There were fetuses with pulmonary hypoplasia that had respiratory movements seen at the majority of ultrasonographic examinations. PMID- 2240107 TI - Color flow Doppler--a useful instrument in the diagnosis of vasa previa. AB - Vasa previa is associated with an increased perinatal mortality rate and rarely is diagnosed in the antepartum period. We present a case in which vasa previa was correctly diagnosed by use of color flow Doppler imaging. This modality is a valuable adjunct in the evaluation of patients suspected to have vasa previa. PMID- 2240108 TI - Reliability of ultrasonographic formulary in the prediction of fetal weight and survival of very-low-birth-weight infants. AB - Antenatal management of very-low-birth-weight infants often requires difficult obstetric decisions. This study was designed to evaluate the predictive value for neonatal outcome of antenatally acquired estimation of gestational age and ultrasonographically estimated fetal weight or a combination of both in very-low birth-weight infants. Sixty-seven fetuses with estimated gestational ages between 22 0/7 and 28 6/7 weeks were studied ultrasonographically to estimate fetal weight. A comparison of accuracy of estimated fetal weight with actual birth weight showed good correlation (r = 0.93). Neonatal outcome of these infants was analyzed by estimated gestational age and estimated fetal weight. Estimated gestational age and estimated fetal weight greater than 25 weeks and greater than 750 gm were associated with 50% survival, respectively. However, when both of these conditions were met survival reached 85%. This information may be useful to guide antepartum management decisions in this very-low-birth-weight group. PMID- 2240109 TI - Hyperadrenergic orthostatic intolerance as a result of postpartum blood loss. AB - This article describes a young women in whom orthostatic intolerance developed as a result of protracted postpartum vaginal bleeding. The cardiovascular abnormalities were unresponsive to usual treatment measures, and she required combination therapy directed at increasing plasma volume and decreasing sympathetic nervous system activity. After resolution of her symptoms, the patient required no long-term therapy. Chronic blood loss has not been reported as a cause of this syndrome. PMID- 2240111 TI - Intrauterine Listeria infection: prenatal diagnosis by biophysical assessment and amniocentesis. PMID- 2240110 TI - Cervicovaginal microflora and pregnancy outcome: results of a double-blind, placebo-controlled trial of erythromycin treatment. AB - Available information suggests that some instances of preterm birth or premature rupture of membranes are associated with clinically unrecognized infection and inflammation of the lower uterine segment, decidua, and fetal membranes. Various cervicovaginal microorganisms have been recovered from these sites. Many of these microorganisms produce factors that may lead to weakening of the fetal membranes, release of prostaglandins, or both. This study evaluated the presence of various lower genital tract microflora and bacterial conditions in 229 women enrolled in a double-blind, placebo-controlled trial of short-course erythromycin treatment at 26 to 30 weeks' gestation to prevent preterm birth. Demographic, obstetric, and microbiologic parameters were prospectively evaluated. Premature rupture of membranes occurred less frequently (p less than 0.01) among women who received erythromycin (6%) versus placebo (16%). Preterm premature rupture of membranes also occurred less frequently, although not significantly (p = 0.3) in patients who received erythromycin (2%) versus placebo (5%). Erythromycin treatment significantly decreased the occurrence of premature rupture of membranes among women who were initially positive for Chlamydia trachomatis infection. Logistic regression analysis demonstrated that C. trachomatis (p = 0.05; odds ratio, 9), vaginal wash phospholipase C (p = 0.08; odds ratio, 6) and prior preterm birth (p = 0.007; odds ratio 17) were associated with increased risk of preterm birth. Bacterial vaginosis, Mycoplasma hominis, Ureaplasma urealyticum were not significantly associated with increased risk of preterm birth or preterm rupture of membranes. These findings support a role for selected lower genital tract microflora in preterm birth and premature rupture. Large controlled treatment trials of specific infections or conditions associated with preterm birth and premature rupture of membranes are required to confirm the value of antimicrobial treatments in prevention of microbial-associated preterm birth. PMID- 2240112 TI - Pregnancy outcomes among mothers infected with human immunodeficiency virus and uninfected control subjects. AB - Between June 26, 1985, and Feb. 24, 1989, 101 seropositive pregnant women and 129 seronegative pregnant women from the same prenatal clinics in Brooklyn and the Bronx were recruited into a prospective study of human immunodeficiency virus infection in pregnant women and their offspring. This report details the course of pregnancy and short-term neonatal outcomes of 91 seropositive women and 126 seronegative women who gave birth during the study period. Seropositive mothers were significantly more likely to have sexually transmitted diseases (17.6% vs 7.1%, p = 0.017) and medical complications (43.0% vs 25%, p = 0.006) during pregnancy. No other obstetric complications (e. g., chorioamnionitis, endometritis, toxemia, or placental problems) were associated with serologic status. After controlling for confounding variables (drug use, tobacco use, age of mother, and clinic), we found that the mother's serologic status was not significantly associated with birth weight, gestational age, head circumference, or Apgar scores among live infants. For example, after adjustment on confounders we found that children born to seropositive mothers weighed about 7 gm more than children of seronegative mothers (95% confidence interval, -180 to 194 gm). We conclude that in this population human immunodeficiency virus infection has little demonstrable impact on the status at birth of live neonates. PMID- 2240113 TI - Direct analysis of uncultured cytotrophoblastic cells from second- and third trimester placentas: an accurate and rapid method for detection of fetal chromosome abnormalities. AB - Transabdominal chorionic villus sampling can be readily used for detection of fetal chromosome abnormalities in the second and third trimesters of pregnancy. Although culture of chorionic villi offers little advantage over cultured amniotic fluid cells with respect to time required to obtain results, cytogenetic analysis of chorionic villi by direct analysis of uncultured cytotrophoblastic cells offers clear advantages because of the very short time required to obtain results. To determine whether direct analysis of uncultured cytotrophoblastic cells from second- and third-trimester placentas can routinely provide rapid and accurate assessment of fetal status, we evaluated chorionic villus specimens obtained from 57 placentas; 49 placentas were sampled in the second trimester whereas eight were sampled in the third trimester. Direct preparations yielded karyotypes in 56 (98.2%) preparations; all results of direct analyses were available within 72 hours and, when requested, within 12 hours. All results were confirmed by chromosome analysis of cultured mesenchymal core cells or cultured fetal tissue. We conclude that direct analysis of cytotrophoblastic cells from second- and third-trimester placentas is a very rapid and accurate method for determining fetal chromosome status that is comparable with, if not superior to, percutaneous umbilical blood sampling. PMID- 2240114 TI - Perinatal mortality in Victoria, Australia: role of group B Streptococcus. AB - Group B beta-hemolytic streptococcus is the most common infective cause of neonatal morbidity and mortality. It is therefore surprising that no agreement exists for an approach to its prevention. There is also increasing evidence that occult infection may play an etiologic role in premature rupture of the membranes and preterm labor. In this report we review the role of group B beta-hemolytic streptococcal sepsis as a cause of perinatal wastage in the state of Victoria, Australia during the period 1982 to 1987. Group B beta-hemolytic streptococcus accounted for 1.7% of overall perinatal deaths, and for 30.3% (77 of 254) perinatal deaths directly attributable to infection. By comparison, over the same 6-year period, erythroblastosis accounted for 0.5% of perinatal wastage and there were only two deaths as a result of congenital syphilis. The true incidence of lethal group B beta-hemolytic streptococcal infection is probably greater because of the absence of histologic and bacteriologic studies in many perinatal deaths. We believe that intrapartum chemoprophylaxis with penicillin of all group B beta hemolytic streptococcus-positive carrier mothers would significantly reduce neonatal morbidity and mortality from this cause. PMID- 2240115 TI - A comparison of sperm antibody assays. AB - Cytotoxicity and Immunobead-binding immunoglobulin G assays agreed in 81% of sera from infertile men (n = 173), 74% of sera from their wives, 75% of seminal plasma, and 82% of cervical mucous samples (p less than 0.001; chi 2 analysis of positive and negative results) when tested against sperm from the same donors. Cytotoxic and immunofluorescent IgG antibody results agreed in 79% of sera from men and women, 76% of seminal plasma, and 76% of cervical mucus (p less than 0.001; chi 2 analysis of positive and negative results). Titers or percent binding of sperm by cytotoxicity, hemagglutination, and IgG Immunobead-binding or immunofluorescence assays in serum and secretions of husbands and wives correlated (p less than 0.001). A significantly increased number of positive results was observed in cytotoxic and Immunobead-binding IgG assays when the husbands' and donors' sperm were used rather than donors' sperm alone. On the basis of this study we conclude: (1) that cytotoxicity, Immunobead-binding IgG, and immunofluorescent IgG sperm antibody assays correlate when sperm from the same source are used, (2) that women's isoimmunity to husbands' sperm is associated with their husbands' autoimmunity to sperm irrespective of the assay, and (3) that it is desirable to use sperm from the husbands and nonautoimmune fertile men in these assays. PMID- 2240116 TI - Extensive vulvar and vaginal varicella necessitating abdominal delivery. AB - Maternal varicella occurs in fewer than five per 10,000 pregnancies in the United States. A case is reported in which markedly painful, extensive vulvar and vaginal ulcers prevented cervical examination, and cesarean section was performed with the patient under general anesthesia. PMID- 2240117 TI - The role of fetal membranes in regulating production, transport, and metabolism of prostaglandin E2 during labor. AB - The level of prostaglandin E2, a potent stimulator of myometrial contractions, increases in amniotic fluid during labor. We tested whether amniotic prostaglandin E2 crosses the reflected fetal membranes to the myometrium during labor. Disks of amnion, chorion-decidua, and amnion chorion-decidua from 10 term pregnancies before labor and nine vaginal deliveries after normal spontaneous labor were incubated in two-sided perfusion chambers in the absence or presence of 1 mumol/L indomethacin, or in the presence of a bolus of prostaglandin E2 and radiolabeled prostaglandin E2 added to the fetal chamber. Net amniotic prostaglandin E2 increased significantly (p = 0.003) after labor. However, there was no significant difference in prostaglandin E2 concentrations on the maternal side of amnion chorion-decidua between labor conditions. High-pressure liquid chromatography identified the transport of intact tritiated prostaglandin E2 across amnion but not across chorion-decidua or amnion chorion-decidua in which prostaglandin E2 was completely metabolized. Because of 15-hydroxyprostaglandin dehydrogenase activity in chorion, we suggest that amniotic prostaglandin E2 transport to the myometrium is impaired. Thus the increase in prostaglandin E2 production that occurs in amnion tissue after labor commences does not result in an increase in prostaglandin E2 concentration on the myometrial side of the fetal membranes in the in vitro preparation. PMID- 2240118 TI - Surgical staples in cesarean section: a randomized controlled trial. AB - This randomized controlled trial compares the use of the Auto Suture Poly CS 57 disposable surgical stapler (n = 98) with standard hysterectomy (n = 102) in low transverse cesarean sections. Subjective assessment of blood loss by the surgeon resulted in lower mean (+/- SEM) total blood loss estimates in the stapled group (492 +/- 24 ml) than in the nonstapled group (579 +/- 38 ml) (p = 0.05). However, surgeon's estimation of blood loss as a result of the hysterotomy and blood loss estimated by the hemoglobin deficit measured on the second postoperative day did not significantly differ between the two groups. The use of the stapling device tended to lengthen the total operating time, which averaged 42.5 minutes in the group with the staples and 39.2 minutes in the group with the standard hysterotomy (p = 0.05). The risk of febrile morbidity, the frequency of endometritis, and the length of hospitalization were similar in the two groups. Our results do not support the routine use of the Auto Suture Poly CS 57 disposable surgical stapler in low transverse cesarean sections. PMID- 2240119 TI - The associated anomalies that determine prognosis in congenital omphaloceles. AB - Cogenital abdominal wall defects such as omphaloceles can be recognized by fetal ultrasonography. To determine whether associated anatomic features may be useful in determining fetal prognosis, a retrospective study was performed over a 5-year period. There were 28 cases of omphalocele; 16 were larger than 5 cm and classified as giant, and the remainder were considered small. Eleven of the 12 infants with small omphaloceles survived with minimal neonatal complications. Ten of the 16 infants with giant omphaloceles died because of associated congenital anomalies. These were congenital heart disease, central nervous system malformations, and diaphragmatic hernias. This review suggests that the prognosis is good when a prenatal diagnosis of giant omphalocele is made and careful fetal ultrasonography, including echocardiography, does not identify heart, central nervous system, or diaphragmatic malformations, even when there is liver herniation into the omphalocele. PMID- 2240120 TI - Ultrasonographic assessment of placental abnormalities. AB - Current ultrasonographic techniques offer a novel approach for the identification of a wide variety of placental abnormalities usually described postnatally by the pathologist. Placental vascular lesions, placental tumors, and abnormal placentation are potentially associated with perinatal complications and their diagnosis in utero may influence the pregnancy management. An ultrasonographic classification of placental lesions that is based on their location, size, echogenicity, and number is proposed. Repeated ultrasonographic examination, together with biologic investigations, is important for the prenatal differential diagnosis of most these lesions and for full understanding of their pathophysiologic characteristics and significance. PMID- 2240121 TI - Preferential mitogenic activity for myoblast-like cells can be extracted from uterine leiomyoma tissues. AB - The presence of mitogen(s) in leiomyoma extracts stimulating cells with the fibroblast, myoblast, and osteoblast phenotype was documented. Mitogenic activity in leiomyoma extracts was acid stable and sensitive to tryptic digestion. Reverse phase high-performance liquid chromatography successfully separated mitogen(s) with preferential activity for myoblast cells from mitogens with a broad type of cell specificity and from inhibitors. This leiomyoma-derived preferential activity for myoblasts was absent in identically treated myometrial and endometrial extracts. This suggests that leiomyoma-derived substances with preferential growth factor activity for myoblast-like cells may play a role in the pathophysiologic characteristics of uterine leiomyomas. PMID- 2240122 TI - Platelet activating factor enhances in vitro fertilization of rabbit oocytes. AB - Capacitation of spermatozoa is essential for fertilization. Rabbit spermatozoa are particularly difficult to capacitate in vitro and require treatment with high ionic-strength Brackett's defined medium. Spermatozoa treated with platelet activating factor had significantly higher fertilization rates when compared with nontreated (fresh, twice washed) spermatozoa (63% vs 34%). Fertilization rates of spermatozoa treated with platelet activating factor, although higher than those of high-ionic-strength capacitated spermatozoa, were not significantly different (63% vs 57%). Spermatozoa treated with lyso-platelet activating factor, the biologically inactive form of platelet activating factor, were noted to have fertilization rates similar to those of the untreated (noncapacitated) group. These data show that synthetic platelet activating factor treatment of uncapacitated spermatozoa induces fertilization of rabbit oocytes in vitro in a manner similar to that for spermatozoa capacitated by high-ionic-strength media and significantly higher than that for untreated spermatozoa or after treatment with the biologically inactive form of platelet activating factor (lyso-platelet activating factor). PMID- 2240123 TI - Adhesion formation after ovarian wound repair in New Zealand white rabbits: a comparison of ovarian microsurgical closure with ovarian nonclosure. AB - Thirty female New Zealand white rabbits underwent standard laparotomy. Each ovary was bivalved and hemostasis was achieved with bipolar electrocautery. One ovary was then randomized to the closure group, whereas the other ovary was placed in the nonclosure group. In the closure group, the ovarian capsule was closed with a continuous suture of 8-0 Vicryl absorbable surgical suture material with microsurgical technique. In the nonclosure group, the ovaries were left open. Three weeks later the animals were killed and the ovarian adhesions were graded with a standardized scale by an observer (A. A. T.) blinded to the closure status of the animals. Five control animals underwent sham operations with minimal adhesion formation. Statistical analysis of the study animals by the paired Student t test showed a significantly higher adhesion score on the ovaries that were microsurgically closed compared with the ovaries not closed (p = 0.02). PMID- 2240124 TI - Uterine artery estrogen receptors in the nonpregnant and pregnant guinea pig. AB - Uterine artery, heart, and aorta or carotid specimens of nonpregnant, midpregnant, and term pregnant guinea pigs were examined for estrogen receptors by immunocytochemical methods. Estrogen receptors were found in the nuclei of cells in the endothelial, muscle, and adventitia layers of the uterine artery wall. The concentration of estrogen receptors was slightly higher in nonpregnant and term pregnant animals than in midpregnancy. No estrogen receptors were found in the heart, aorta, or carotid specimens of all animals. These results confirm the uterine artery as a target organ of estrogen action that would eventually lead to arterial functional adaptation in different biologic periods. PMID- 2240125 TI - Discrepancies in hemoglobin levels. PMID- 2240126 TI - Cytogenetic uncertainties surrounding the fragile X in Martin-Bell syndrome. PMID- 2240127 TI - Magnesium sulfate is not an ideal anticonvulsant. PMID- 2240128 TI - Parameters of hypothalamic aging. PMID- 2240129 TI - One case of 45,X abortus with high CA 125 level. PMID- 2240130 TI - Neuromodulatory regulation of gonadotropin-releasing hormone pulsatile discharge in women. AB - The pulsatile release of gonadotropin-releasing hormone and the consequent secretion of gonadotropins are regulated by a complex interplay of steroids, neuropeptides, catecholamines, and environmental factors. Estrogen and progesterone influence the amplitude and frequency of luteinizing hormone pulsatile secretion. These effects lead to both a diurnal variation in pulse frequency, with a lower frequency at night, and variation during the menstrual cycle, with a lower frequency and increased amplitude during the luteal phase. Opioid peptides inhibit the pulsatile discharge of gonadotropin-releasing hormone and luteinizing hormone. The opioid antagonist, naloxone, causes an increase in luteinizing hormone secretion, particularly during the luteal phase. The administration of opioid receptor agonists, such as beta-endorphin, results in a decline in serum luteinizing hormone during the early follicular phase. Corticotropin-releasing factor, which is increased during stress, inhibits pulsatile luteinizing hormone secretion, and this effect can be blocked by the simultaneous administration of naloxone. These observations suggest that corticotropin-releasing factor exerts its effects on luteinizing hormone through an opioidergic intermediary. Endogenous catecholamines such as dopamine inhibit pulsatile luteinizing hormone release; however, the mechanism involved is not clear. PMID- 2240131 TI - Practical aspects of pulsatile gonadotropin-releasing hormone administration. AB - Pulsatile administration of gonadotropin-releasing hormone represents a major advance in the treatment of anovulation in women who fail to ovulate with clomiphene citrate and is an alternative for many women who currently receive human menopausal gonadotropin. Four issues must be addressed before administering pulsatile gonadotropin-releasing hormone: (1) safety, (2) efficacy, (3) convenience, and (4) cost. Each of these issues will be affected by the three major decisions a physician makes with gonadotropin-releasing hormone therapy: (1) patient selection, (2) route of administration, and (3) dose of gonadotropin releasing hormone. The ideal candidate for gonadotropin-releasing hormone therapy is a patient with an absence of endogenous pulsatile gonadotropin-releasing hormone, as seen in hypothalamic amenorrhea. Although women with polycystic ovarian disease can be treated with pulsatile gonadotropin-releasing hormone, a decreased ovulation rate should be expected. The route of administration, intravenous or subcutaneous, and the degree of monitoring can be tailored by the physician to fit each patient's needs. Pulsatile gonadotropin-releasing hormone therapy is a safe, effective, convenient, and economical alternative to human menopausal gonadotropin for ovulation induction in women resistant to clomiphene. PMID- 2240133 TI - Publications of Lorenz E. Zimmerman. PMID- 2240132 TI - Letters of tribute and articles dedicated to Lorenz E. Zimmerman on the occasion of his 70th birthday. PMID- 2240134 TI - Pseudoexfoliative fibrillopathy in the skin of patients with ocular pseudoexfoliation. AB - In addition to its occurrence within the eye, pseudoexfoliative fibrillopathy has been reported in the conjunctiva and around a posterior ciliary artery. To determine whether it has a more diffuse extraocular distribution, we studied skin biopsy specimens ultrastructurally from one to three areas in 13 patients with classic pseudoexfoliation. A fibrillopathy closely resembling that in the eye was found in 11 of the 13 patients. Only one of the 13 control subjects, a 78-year old man with advanced low-tension glaucoma, had a similar fibrillopathy. In the patients with pseudoexfoliation who were more than 70 years of age, the accompanying dermal elastosis made evaluation difficult, because the pseudoexfoliative nodules in the skin occur primarily along elastic fibers, and their morphologic characteristics appeared to be influenced by the elastotic process. These results suggest that pseudoexfoliation is a systemic process related closely to elastosis, and that further search for pseudoexfoliative fibers should be made in the elastic system of the deep tissues and internal organs. PMID- 2240135 TI - Ocular adnexal Kaposi's sarcoma in acquired immunodeficiency syndrome. AB - We examined histopathologically 18 ocular adnexal Kaposi's sarcoma lesions related to acquired immunodeficiency syndrome. These lesions were classified into three types. Type I consisted of thin, dilated vascular channels lined by flat endothelial cells with lumen-containing erythrocytes. Type II featured plump, fusiform, endothelial cells, often with a hyperchromatic nucleus and foci of immature spindle cells and occasional slit vessels. Type III was characterized by large aggregates of densely packed spindle cells with hyperchromatic nuclei, occasional mitotic figures, and abundant slit spaces often containing erythrocytes in between. Clinically, type I and type II tumors were patchy and flat (less than 3 mm in height) and of less than four months' duration. Type III tumors were nodular and elevated (greater than 3 mm in height). We describe the clinical and histopathologic types of Kaposi's sarcoma that may help in diagnosis. PMID- 2240136 TI - Ocular pathologic features of arteriohepatic dysplasia (Alagille's syndrome). AB - Arteriohepatic dysplasia (Alagille's syndrome), an autosomal dominant condition involving jaundice caused by a developmental scarcity of intrahepatic bile ducts, has characteristic cardiovascular, skeletal, facial, and ocular features that distinguish it from extrahepatic biliary atresia and an array of other neonatal intrahepatic cholestatic disorders. Two children who died of this syndrome had prominent Schwalbe's rings with attached iris strands characteristic of Axenfeld's syndrome. Additional histologic findings of iris atrophy and stromal nodules, however, made the designation Axenfeld-Reiger's syndrome more appropriate. Pigmentary retinopathy, degeneration of Bruch's membrane, and prominent lipofuscin deposition in the ciliary muscle noted in one of the patients were not regarded as primary changes of Alagille's syndrome, but were believed to be secondary to acquired deficiency of the fat-soluble vitamins A and E. Early recognition of the ocular changes in arteriohepatic dysplasia is helpful in establishing the proper diagnosis to avoid unnecessary abdominal surgery and institute vitamin therapy. PMID- 2240137 TI - Cholesterol localization in ultrathin frozen sections in Schnyder's corneal crystalline dystrophy. AB - We examined a 57-year-old woman who had bilateral corneal crystalline deposits associated with xanthelasma. The patient's son had bilateral stromal haze. Plasma cholesterol and apolipoprotein A-I and B levels were normal. Histopathologic examination disclosed lipid deposits, particularly in the superficial stroma and Bowman's layer. These deposits stained with oil red O and filipin, a fluorescent probe that specifically detects unesterified cholesterol. Cryoultramicrotomy disclosed more specific ultrastructural localization of unesterified cholesterol with an array of crystals resembling multiple plates in extracellular corneal tissue. PMID- 2240138 TI - Traumatic enucleation for posterior uveal melanoma. AB - Two features of eyes enucleated for posterior uveal melanoma that may serve as indicators for traumatic enucleation and relate to dissemination of tumor cells at the time of enucleation are myelin artifact of the optic nerve head and acute hemorrhage within the tumor. Myelin artifact occurs when crushed optic nerve tissue is squeezed into the eye at the time of enucleation. Intralesional hemorrhage may occur during surgery and may be correlated with fluctuations in intraocular pressure. We reviewed 519 cases of posterior uveal melanoma treated by enucleation between 1950 and 1970. Without knowledge of the follow-up data, we examined histologic sections for myelin artifact, intralesional hemorrhage, subretinal hemorrhage, Callender cell type, size of tumor, necrosis, and scleral or orbital invasion. Neither myelin artifact nor intralesional hemorrhage were independent prognostic risk factors. These findings do not support or refute the hypothesis that excessive trauma during enucleation results in a worse prognosis. PMID- 2240140 TI - Orbital intramuscular schwannoma. AB - In an 8-year-old girl with asymptomatic proptosis, computed tomographic scans showed a large medial orbital mass that contoured the globe anteriorly, bowed the optic nerve laterally, and extended posteriorly to the orbital apex. T1-weighted coronal magnetic resonance images showed the mass to be a diffusely enlarged medial rectus muscle. Histopathologic examination of a medial rectus muscle biopsy specimen disclosed a multinodular, intramuscular schwannoma, separating and infiltrating normal skeletal muscle fibers. The intramuscular location and multinodular configuration of this tumor, together with its occurrence in a child, distinguish it from previous orbital schwannomas. PMID- 2240141 TI - Notes from the dugout. PMID- 2240139 TI - A randomized study of methanol-extraction residue of bacille Calmette-Guerin as postsurgical adjuvant therapy of uveal melanoma. AB - A randomized controlled clinical trial of methanol-extracted residue of bacille Calmette-Guerin adjuvant treatment of posterior uveal melanoma was undertaken. Of 113 patients, 34 patients received adjuvant immunotherapy and 79 patients received no treatment. No difference in survival was observed between the adjuvant-treated group and the control group of patients. This study found that the size of the tumor was a highly significant risk factor for death caused by metastasis of uveal melanomas. The standard deviation of the nucleolar area of the neoplastic cells was a significant risk factor, even though patients with tumors composed of Callender's spindle-type cells were not included in the study. PMID- 2240142 TI - Visual improvement after long-term success of pancreatic transplantation. PMID- 2240143 TI - Duane's retraction syndrome in the fetal alcohol syndrome. PMID- 2240145 TI - Long-term follow-up of facioscapulohumeral muscular dystrophy and Coats' disease. PMID- 2240144 TI - Delayed drug-induced periorbital angioedema. PMID- 2240146 TI - A total orbital floor fracture with prolapse of the globe into the maxillary sinus manifesting as postenucleation socket syndrome. PMID- 2240148 TI - Conjunctivitis caused by Thelazia californiensis. PMID- 2240147 TI - Aplastic anemia with platelet autoantibodies in a patient after taking methazolamide. PMID- 2240150 TI - Corneoscleral rupture ten years after radial keratotomy. PMID- 2240151 TI - Translimbal iris hook for pupillary dilation during vitreous surgery. PMID- 2240149 TI - An unusual case of neurosarcoidosis confirmed by a muscle biopsy specimen. PMID- 2240152 TI - A sutureless self-retaining infusion cannula for pars plana vitrectomy. PMID- 2240153 TI - Liability for intraocular lens calculations. PMID- 2240154 TI - Primate trabeculectomies with 5-fluorouracil collagen implants. PMID- 2240155 TI - Recurrent conjunctival papilloma causing nasolacrimal duct obstruction. PMID- 2240156 TI - Increase of beta 1-6-branched oligosaccharides in human esophageal carcinomas invasive against surrounding tissue in vivo and in vitro. AB - The -GlcNAc beta 1-6Man- (beta 1-6) branched N-glycosidic oligosaccharides expressed on tumor cells have been found to contribute to malignant and metastatic potential in experimental tumor models. Phaseolus vulgaris leukoagglutinin (L-PHA) requires the beta 1-6-linked lactosamine antenna for high affinity binding and was used histochemically to characterize the distribution of these sugar structures in human esophageal squamous cell carcinomas from 42 patients. Leukoagglutinin-reactive carcinoma cells in the invasive tumors were distributed predominantly on the outer surface of the tumor adjacent to the surrounding tissue. Furthermore, when TE 1 cells, a human esophageal squamous cell carcinoma line, were cultured in a collagen gel matrix to obtain colonies in a three-dimensional form, these colonies exhibited high affinity for L-PHA binding only in the outer cell layer facing the collagen matrix, unrelated to the cell growth cycle. These findings suggest that the increase in beta 1-6-branched oligosaccharides in esophageal carcinomas is an important trait of the tumor in the invasion into the surrounding tissue. PMID- 2240157 TI - Mechanisms of edema formation in experimental autoimmune encephalomyelitis. The contribution of inflammatory cells. AB - Most of the central nervous system (CNS) endothelium regulates the passage of solutes and functions as a blood-brain barrier (BBB). During experimental autoimmune encephalomyelitis (EAE), an inflammatory demyelinating disease of the CNS, loss of BBB function occurs. The authors have previously shown an increase in endothelial transcytotic activity associated with decreased mitochondrial content as evidence of BBB dysfunction in EAE. These changes occurred in the capillary bed and correlated with CNS edema and clinical signs. In the present report, a fixation procedure before infusion of the intravascular tracer horseradish peroxidase (HRP) in rats at the height of clinical EAE has been used. In these animals, tracer leakage was only noted in inflamed venules with diameters of 12 to 19 mu. The authors detected several mechanisms of passive leakage: 1) increased junctional permeability; 2) increased interendothelial space; 3) leakage alongside migrating inflammatory cells. Some small capillaries showed necrotic changes with minimal tracer leakage. This report demonstrates that BBB disruption also occurs via nonendocytic mechanisms that may be induced by inflammatory cells. PMID- 2240158 TI - Histologic similarity of murine colonic graft-versus-host disease (GVHD) to human colonic GVHD and inflammatory bowel disease. AB - In a study designed to determine which T-cell subsets are involved in the development of murine graft-versus-host disease (GVHD), a prospective histologic analysis of gastrointestinal involvement was performed. In C57BL/6JXDBA/2F1 (B6D2F1) recipients of DBA/2 donor spleen and bone marrow cells, the colonic histologic findings were found to be similar in many respects to the histologic findings reported in human colonic GVHD and were much more severe and diffuse than were the abnormalities of the small intestine. Host irradiation before transplantation was found to play an additive or synergistic role in the development of GVHD. Furthermore the histologic features noted in DBA/2----B6D2F1 murine colonic GVHD suggest that bone marrow and spleen cell transplantation in this strain combination may be a useful model for studying the immunologic mechanisms involved in human inflammatory bowel disease. Thus severe colonic disease noted during the course of DBA/2----B6D2F1 murine GVHD was found to have significant histopathologic similarities to both human GVHD enteropathy and other inflammatory diseases of the human colon. PMID- 2240159 TI - Pathogenesis of antigen-induced arthritis in mice deficient in neutrophil elastase and cathepsin G. AB - The contribution of neutrophil-derived elastase and cathepsin G to joint pathology has been examined in immune arthritis in the mouse. Neutrophils from beige mice are genetically deficient in lysosomal elastase and cathepsin G, but have normal levels of the acid hydrolases, beta-glucuronidase, and N-acetyl-beta glucosaminidase. The development of antigen-induced arthritis in normal mice has been compared with that in beige mice. The pattern of synovitis (both leukocyte accumulation and plasma leakage) were indistinguishable in normal and beige mice. Cartilage proteoglycan depletion was quantified by measuring the decrease in safranin O staining intensity, and this, too, was unaltered in mice lacking elastase and cathepsin G. These results suggest that neutrophil elastase and cathepsin G do not contribute to these aspects of joint pathology in antigen induced arthritis in the mouse. PMID- 2240161 TI - Development of multiple necrotizing enteritis induced by a tumor necrosis factor like cytokine from lipopolysaccharide-stimulated peritoneal macrophages in rats. AB - We report the development of an animal model of multiple necrotizing enteritis (MNE) in rats. When rats were injected directly with a culture supernatant of lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages into the abdominal aorta, the overt pathologic lesions of MNE developed within 30 minutes after injection. The rats showed an elevated level of blood fibrinogen degradation product content even 30 minutes after injection. Furthermore the rats that were pretreated intravenously with heparin sulfate did not develop MNE, indicating the acute disturbances of blood microcirculation in the intestine. Multiple necrotizing enteritis was developed also by the injection with recombinant tumor necrosis factor (rTNF) but rarely was observed with even a high dose of recombinant interleukin-1 (rIL-1) or platelet-activating factor (PAF). The supernatant was cytotoxic in vitro to TNF-susceptible LM and many other cells but was less cytotoxic to the TNF-resistant LR line. Partial purification of the supernatant suggested that the supernatant contained a cytokine that has biochemical features of TNF. Furthermore polyclonal anti-TNF antibody could inhibit not only the cytotoxicity in vitro but also MNE development in vivo by this factor. These data strongly indicate that MNE possibly could be caused by a TNF-like cytokine produced by macrophages that are stimulated by the endotoxin. PMID- 2240160 TI - Metaplastic change in mesenchymal stem cells induced by activated ras oncogene. AB - 3T3 T murine mesenchymal stem cells have the potential to differentiate into a variety of different cell types even though they show a predilection to undergo adipocyte differentiation in vitro. The possibility that the activated c-Ha-ras (EJras) oncogene might influence the pathway of differentiation of these stem cells is investigated in the current study. Activated ras oncogene was transfected and stably expressed in 3T3 T cells; assays then were performed to determine its effect on differentiation. The results show that all EJras transfected cell lines lose their ability to differentiate to adipocytes and instead differentiate into cells that express many characteristics of macrophages. Such cells contain numerous cytoplasmic granules, extensive nonspecific esterase activity, and anchorage-independent growth. The modulation of differentiation pathway from an adipocyte lineage to a macrophagelike cell lineage does not result from the transforming effect of EJras, because a nontransformed cell clone that expresses p21EJras protein also exhibits this modified differentiation pathway. These data suggest that the EJras oncogene specifically modulates the differentiation pathway of 3T3 T mesenchymal stem cells. This experimental system should therefore provide an excellent model to evaluate the mechanistic role of EJras in the process of metaplasia. PMID- 2240162 TI - Ultrastructural localization of proteinase 3, the target antigen of anti cytoplasmic antibodies circulating in Wegener's granulomatosis. AB - To investigate the distribution of proteinase 3, the target antigen of anti cytoplasmic antibodies (ACPA or C-ANCA), within the organelles of resting normal human polymorphonuclear leukocytes and monocytes, the authors used immunocytochemical techniques on thin frozen sections. To obtain valuable tools for immunolabeling, two murine monoclonal antibodies (MAbs) directed against the ACPA antigen were produced. In neutrophils, the authors observed immunogold label for the ACPA antigen, predominantly in myeloperoxidase-positive azurophil granules, and in smaller amounts on the plasma membrane. In monocytes, the ACPA antigen could be detected in small granules, which occasionally also contained myeloperoxidase, and rare labeling was found on the monocyte membrane. The finding that the ACPA antigen is expressed on the plasma membrane of neutrophils and monocytes, thereby becoming accessible to circulating autoantibodies, supports the supposition that ACPA are not only markers of disease activity, but also are involved in the pathogenesis of Wegener's granulomatosis. PMID- 2240163 TI - A,B blood group antigens in tissues of AB heterozygotes. Emphasis on normal and neoplastic urothelium. AB - The tissue distribution of the A and B blood group antigens was studied in 41 individuals with the heterozygous AB red blood cell (RBC) phenotype. A total of 134 biopsies from a variety of normal tissues (94 from urothelium and 40 from other tissues) were examined. In addition, changes in the expression of these antigens associated with neoplastic transformation were evaluated in 70 biopsies from transitional cell carcinomas of 19 AB heterozygous patients. There was heterogeneity in the distribution of tissue A and B antigens, depending on the cell type, as well as among cells of the same type. Ninety-one percent of AB heterozygotes expressed both A and B antigens in normal epithelial cells, with a mosaic distribution clearly apparent in 50% of these individuals. In 21% of these subjects, the A antigen was undetectable in the vascular endothelial cells in all biopsies from several organs. In most (79%) transitional cell neoplasms, only one of the two antigens was consistently expressed. The results of this study may have implications for the clonal or specific gene deletion theories of neoplasia. They also demonstrate the existence of a subgroup of AB individuals in whom the A antigen is absent specifically from the vascular endothelium. PMID- 2240164 TI - Endotoxin-induced cytokine gene expression in vivo. II. Regulation of tumor necrosis factor and interleukin-1 alpha/beta expression and suppression. AB - Tumor necrosis factor alpha (TNF alpha) mRNA is present in a preformed intracellular pool in the spleen, liver, and small bowel of naive rats. Endotoxin (Salmonella typhus lipopolysaccharide) injected intravenously induces little or no increase in whole-organ TNF mRNA levels at 15', 30', 1 degree, 2 degrees, or 4 degrees, whereas serum TNF levels are markedly elevated at 1 and 2 hours. Dexamethasone pretreatment of rats suppresses LPS-induced serum TNF concentrations, but does not suppress TNF mRNA levels in the spleen or bowel. Tachyphylaxis experiments demonstrate that a second injection of endotoxin 2 hours after an initial injection fails to induce a second peak of serum TNF, although TNF mRNA levels in the spleen and bowel remain at the levels found in naive rats. Corynebacterium parvum upregulates endotoxin-induced serum TNF release and intravenous injection of IL-1 induces the release of serum TNF but neither alters whole-organ TNF mRNA levels. Interleukin-1 alpha (IL-1 alpha) mRNA was not constitutively detected in whole-organ RNA preparations of the spleen, liver, and small bowel of naive rats. Endotoxin induces IL-1 alpha mRNA most easily appreciated in the spleen beginning at 1 hour, peaking at 2 to 4 hours, and disappearing by 6 hours. Interleukin-1 beta (IL-1 beta) mRNA was not constitutively detected in the organs examined or was present in small amounts. Endotoxin induces IL-1 beta mRNA beginning at 0.5 hours, peaking at 1 hour, and disappearing by 6 hours. Dexamethasone pretreatment prevents the LPS-induced appearance of IL-1 alpha mRNA and suppresses but does not completely inhibit the appearance of IL-1 beta mRNA. C. parvum upregulates endotoxin-induced IL-1 mRNA expression. Intravenous injection of TNF or IL-1 both induce IL-1 mRNA expression. In conclusion, TNF mRNA is constitutively expressed and TNF mRNA levels as analyzed in whole-organ RNA preparations do not change in concert with serum TNF protein levels during conditions of endotoxemia, dexamethasone treatment, tachyphylaxis, priming with C. parvum, or after injection of IL-1. In contrast, IL-1 mRNA expression during endotoxemia, dexamethasone treatment, priming with C. parvum, or after injection of TNF or IL-1 shows clear increases and decreases in whole-organ RNA preparations. PMID- 2240166 TI - Protein A-gold immunoelectron microscopic study of amyloid fibrils, granular deposits, and fibrillar luminal aggregates in renal amyloidosis. AB - Glomeruli of archival renal biopsies, stored frozen at -70 degrees C, from three patients with amyloid were examined by protein A-gold immunoelectron microscopy. In one with both fibrillar and granular deposits from a 'skin popper' drug abuser, the granular deposits were labeled with anti-IgG, while the fibrillar deposits were labeled with anti-amyloid-A (AA) protein and amyloid P component (AP), suggesting coexisting immune complex disease and AA due to different, but possibly related, pathogenesis. In studies using double-label immunostaining of primary amyloidosis-lambda light chain type (AL) and AA associated with Crohn's disease, AP occurred as widely separated single units along the amyloid fibrils and represented 1.5% and 6.5% of the total gold label in AL and AA, respectively, while the major fibril protein was labeled in single rows, similar to beads on a string. Fibrillar aggregates in the capillary lumens were labeled similarly by antisera to the major protein and AP and appeared to be contiguous with the fibrillar deposits at the glomerular basement membrane (GBM)-luminal interface, suggesting intravascular fibrillogenesis. PMID- 2240165 TI - Flow cytometric analysis of the mechanism of methylmercury cytotoxicity. AB - Flow cytometric analysis of murine erythroleukemic cells (MELC) exposed in vitro to 2.5 to 7.5 mumol/l (micromolar) methylmercury (MeHg) reveals a dose-dependent decrease in the rate of DNA synthesis (rate of passage through the S phase of the cell cycle), manifested as the accumulation of most of the cells in the S phase, and a modest accumulation of cells in the G2/M phase of the cycle. Light microscopy reveals a progressive increase in chromosomal damage (condensation, pulverization). At or above 10 mumol/l MeHg, progression through all the phases of the cell cycle is blocked and mitotic cells are arrested irreversibly in anaphase, with most exhibiting arrangement of chromosomes in a wreathlike ring formation. Also the cells exhibit both nuclear propidium iodide (PI) fluorescence (indicative of loss of viability) and concurrent cytoplasmic carboxyfluorescein (CF) fluorescence (viable cells exhibit CF fluorescence and exclude PI). In addition, there is a dose-dependent increase in cellular refractive index (90 degrees light scatter), an apparent decrease in cell volume (axial light loss), and progressive resistance to detergent (NP-40)-mediated cytolysis. Resistance to detergent-mediated cytolysis is indicative of fixation (protein denaturation, cross-linking, and so on) of the plasma membrane/cytoplasm complex. Our findings indicate that DNA synthesis is the primary target of MeHg cytotoxicity and that apparent targets and degree of cytotoxicity are a complex function of dose. PMID- 2240167 TI - Cyclocreatine inhibits the production of neutrophil chemotactic factors from isolated hearts. AB - This study was designed to determine the effect of cyclocreatine on the release of neutrophil chemotactic factors (NCF) from isolated rabbit hearts. We tested the hypothesis that if ischemia is important for the formation of NCF from the myocardium, then blocking (or delaying) ischemic changes with cyclocreatine should inhibit the release of NCF. Two models were used, including (1) perfusion of rabbit hearts (Langendorff apparatus) with oxygenated (95% oxygen) Krebs Henseleit buffer (K-H buffer) containing 5% cyclocreatine for 120 minutes, and (2) incubating hearts with phosphate-buffered saline (PBS) containing 5% cyclocreatine for 120 minutes. For both models, rabbits were injected intravenously with 10 ml of 5% cyclocreatine solution 30 minutes before the animals were killed and the hearts removed. Control rabbits were injected with 5% creatine solution or saline for 30 minutes before perfusing hearts with K-H buffer or incubating with PBS. Chemotactic activity was assayed in the perfusates and supernatants using modified Boyden chambers and rabbit peritoneal neutrophils as indicator cells. The chemoattractant f-Met-Leu-Phe (f-MLP) was the positive control for a 100% response rate. Isolated hearts perfused with cyclocreatine showed significantly lower chemotactic activity (ie, 1.24 +/- 1% f-MLP; P less than 0.0001) compared to hearts perfused with K-H buffer (129 +/- 18%) or creatine (227 +/- 42%) (mean +/- standard error). Similar results were obtained using incubated hearts. Next the effect of cyclocreatine on neutrophils in the Boyden chamber was determined and it was found that it did not alter neutrophil migration, which excludes a direct inhibitory effect on the cells. Furthermore supernatant from cyclocreatine-treated hearts did not inhibit neutrophil chemotaxis to C5a, indicating absence of a chemotaxis inhibitor in this preparation. Results of these studies suggest that the observed low activity recovered in perfusate and supernatant of cyclocreatine-treated hearts is a result of reduction in the synthesis and/or release of the factors from myocardial tissues. Similar to previously established data, cyclocreatine treatment significantly preserved myocardial nucleotide levels (ie, adenosine triphosphate and creatine phosphate), which supports our hypothesis that the formation of NCF is ischemia dependent and that maintaining elevated levels of myocardial energy nucleotides reduced chemotactic factor release. PMID- 2240168 TI - Immunocytochemical localization of progesterone receptors in endocrine cells of the human pancreas. AB - Progesterone receptors (PgR) have been immunocytochemically localized in the nuclei of several (40% to 75%) endocrine cells of the human pancreas and in a more variable number of neoplastic cells of 7 of 18 endocrine pancreatic tumors. Conversely the exocrine epithelial cells of the pancreas did not exhibit any PgR immunoreactivity in normal as well as in different pathologic conditions, including pancreatic adenocarcinomas. Estrogen receptors were not detected in any of the pancreatic samples investigated. Double immunocytochemical experiments have documented that PgR immunoreactivity in normal Langerhans islets is a consistent feature of most (75%) glucagon-producing A cells, of approximately 5% to 20% of insulin-producing B cells, and of a variable percentage of pancreatic polypeptide (PP)-producing cells, ranging from 5% to 70%. These figures were not affected by the sex, age, or underlying disease of the patients. The reported findings corroborate previous clinical and experimental evidence indicating that sex steroid hormones may have some regulatory effects on the functional activity of the endocrine pancreas. PMID- 2240169 TI - Paroxysmal positional vertigo: what the patient needs to know. PMID- 2240170 TI - Homograft tympanoplasty: the Iowa experience. AB - Homograft tympanic membranes have been used in tympanoplasty for nearly 30 years. Reported anatomical success rates vary from 50 to 100 percent. One hundred and one homograft tympanoplasty procedures were performed at the University of Iowa over the 10-year period of July 1978 through June 1988. The anatomical success rate was 76 percent. Hearing results were satisfactory in 86 percent of cases. The homograft tympanic membrane, with or without ossicles, has proven to be a highly satisfactory modality for the reconstruction of the severely ravaged middle ear. PMID- 2240171 TI - Immunohistochemical localization of vimentin and S-100 antigen in small acoustic tumors and adjacent cochlear nerves. AB - To clarify the involvement of cochlear nerves in small acoustic tumors, we used immunoperoxidase techniques to determine the presence and distribution of vimentin and S-100 antigens in two acoustic tumor specimens and a transected vestibular nerve. Schwann cells and acoustic tumor cells failed to react positively with monoclonal antibody to vimentin. Reaction was observed in mesenchymal-appearing cells within both the normal nerve and the acoustic tumors, predominantly in association with blood vessels. Normal schwann cells and acoustic tumor cells reacted with polyclonal antibody to S-100 antigen with a similar, uniform distribution. Mesenchymal-appearing cells did not react with antibody to S-100. Immunostaining of a vestibular nerve from a Meniere's disease patient, used as a control, did not differ significantly from nerves adjacent to acoustic tumors. Because tumor cells and normal schwann cells stained similarly with antibody to S-100, it was not possible to establish with certainty if tumor cells invaded adjacent nerves. PMID- 2240172 TI - Effects of electrode placement on the auditory brainstem response using ear canal electrodes. AB - The effects of electrode placement on the latency and amplitude of the auditory brainstem response (ABR) were investigated in normal-hearing subjects. Ear canal (EC) electrodes were used in conjunction with surface electrodes to obtain ABRs. Three electrode combinations were evaluated: (1) vertex-EC-EC; (2) vertex-EC neck; and (3) forehead-EC-neck. Absolute and interwave latencies and absolute and relative amplitudes were computed for Waves I, III, and V at 75 dB SL. Standard errors of measurement (SEmeas) revealed excellent test-retest reliability for latency (SEmeas = 0.06 ms) but only fair reliability for amplitude (SEmeas = 55 nv). No reliability differences were observed among the three electrode combinations. No significant latency or interwave latency differences were found among the three montages. No amplitude differences were found for Waves I and III among the montages. However, the Wave V amplitude was larger for the vertex-EC-EC and vertex-EC-neck montages than for the forehead-EC-neck montage. Because the vertex-EC-EC montage does not require additional electrodes on the contralateral neck, this montage is recommended. PMID- 2240173 TI - The fallopian canal and facial nerve in sclerosteosis of the temporal bone: a histopathologic study. AB - Sclerosteosis is an uncommon subtype of osteopetrosis that is frequently associated with recurrent facial nerve palsy. Because of the need for detailed measurements of the fallopian canal and facial nerve in this disease, a study was carried out using a new method of surface area measurement. The results show narrowing of the fallopian canal and facial nerve in the labyrinthine, distal tympanic and mastoid segments. Maximum surface area loss occurred in the labyrinthine segment for both the canal and nerve. In addition, bony occlusion of the stylomastoid artery was found. From these findings we conclude that ischemia and bony compression are the underlying causes of recurrent facial palsy in this disease. We also conclude that because the labyrinthine segment is the most severely affected, surgical decompression must include this portion of the fallopian canal. PMID- 2240174 TI - Early onset sensorineural hearing loss: association studies with major histocompatibility class III (complement) markers. AB - In 39 families with at least one child suffering from moderate or severe bilateral sensorineural hearing loss (SNHL), major histocompatibility complex (MHC) class III complement phenotypes were retrospectively determined by standard methods; MHC class I segregation data was also available. The families were treated in the Hospital for Communication Disorders and selected for the HLA-B16 and B18 specificities, respectively. Haplotype and allele frequencies were derived from segregation analysis in the families. From 31 unrelated children with random and familiar forms of SNHL significant deviations in the distribution were seen for the following MHC class III alleles using as a control population 60 German healthy individuals: duplicated C4A alleles (C4"DA") p = 0.009, silent C4A alleles (C4A*Q0) p = 0.006, duplicated heavy C4 beta-chain alleles (C4 beta"DHH") p = 0.0003, and silent C4 beta-chain alleles (C4 beta*Q0) p = 0.0075. In serum samples from patients with an assumed genetic disposition according to clinical criteria indications for an association were found for C4"DA" (p = 0.03), C4A*Q0 (p = 0.003), C4B*3 (p = 0.046), C4 beta"DHH" (p = 0.004), and C4 beta*Q0 (p = 0.02). The underrepresentation of C4A*Q0 may be an indicator for aberrant or duplicated C4 alleles on the same haplotype or exhibit a protection mechanism for acquiring the inheritable forms of early onset SNHL. PMID- 2240175 TI - Gamma knife: hydrocephalus as a complication of stereotactic radiosurgical treatment of an acoustic neuroma. AB - Stereotactic radiosurgery is at present being marketed as a reliable alternative to conventional tumor removal in patients with acoustic neuromas. Hearing preservation is possible and treatment modality is presented as being very low. A case history is presented, in which a patient with an 18 mm tumor and normal hearing developed severe hydrocephalus and dizziness 9 months after irradiation, in addition to losing her hearing. Whether the Gamma knife is to be considered a reliable alternative to surgical removal of acoustic neuromas is discussed. PMID- 2240176 TI - Use of the Million Clinical Multiaxial Inventory in evaluating patients with severe tinnitus. AB - The Million Clinical Multiaxial Inventory (MCMI) was evaluated as a diagnostic tool for personality disorder among 41 patients with severe tinnitus. Nearly 70 percent of the subjects demonstrated a personality disorder. Nearly half of the patients fell into one of two categories; dependent/submissive or the narcissistic category. Other important features include a high incidence (24%) of severe anxiety. One-third of the patients had a complaint tendency but 50 percent had a denial problem. We have found the MCMI to be easy to administer and evaluate and it provides the clinician with useful information. We believe that more routine use of this or similar instruments would improve the treatment outcome of tinnitus sufferers by bringing into focus the important psychological factors found in each patient. PMID- 2240177 TI - Dysequilibrium and audiovestibular function in panic disorder: symptom profiles and test findings. AB - Patients with panic disorder commonly report symptoms of dizziness and imbalance. We studied the relationship between objective measures of audiovestibular function, phenomenologic, and self-report measures of dysequilibrium and related somatic symptoms in a sample of panic disorder patients with and without agoraphobia, unselected for the complaint of dysequilibrium. Of seventeen patients evaluated by electronystagmography, 71 percent exhibited abnormal vestibular test findings. These latter patients had higher total anxiety ratings than patients without vestibular abnormalities. We conclude that patients with panic disorder warrant evaluation of audiovestibular function. PMID- 2240178 TI - Autoimmune sensorineural hearing loss: a preliminary experimental study. AB - The aim of this study was to compare cochlear alterations produced by induction of anti-type II collagen antibodies with alterations produced by passive transfer of anticochlear antibodies. Guinea pigs (GP) were used. The anticochlear antibodies were obtained by injecting GP membranous cochlea plus Freund's adjuvant into rabbits. After partial purification of the immunoglobulins, the antibodies (20 mg) were injected intramuscularly into 10 normal GP. A second group of 10 normal GP received intramuscular injections of purified chicken type II collagen (1 mg) plus Freund's adjuvant. A control group of 10 normal GP was studied under the same conditions without any stimulus. The cochlea function was analysed with brainstem evoked audiometry (BERA). The structural study was carried out by immunofluorescent and hematoxylin preparations. The results showed structural alterations in both experimental groups (loss of nucleus in the spiral ganglion); however, significant changes in the BERA were not found. Only increase of the latency of wave I could be seen. These preliminary results support the hypothesis that antibodies to collagen type II may play an important role in human autoimmune sensorineural hearing loss, but the possible existence of other cochlear antigens is discussed. PMID- 2240179 TI - Hyperbaric oxygen management of chronic staphylococcal osteomyelitis of the temporal bone. AB - Hyperbaric oxygen (HBO) has proven efficacious in the adjunct management of selected otolaryngologic problems: radiation therapy-induced osteoradionecrosis of the temporal bone, malignant external otitis, mandibular osteoradionecrosis and refractory osteomyelitis, soft tissue head and neck necrotizing fasciitis, compromised skin flaps and grafts, acute air or gas embolism, and otologic barotrauma. Herein is described the management of an insidious Staphylococcus aureus osteomyelitis of the temporal bone by pre- and postoperative HBO in conjunction with surgical debridement. The possible application of angiogenic agents and tetracycline bone-labeling in combination with hyperbaric oxygen therapy in the management of refractory neurotologic disease will be discussed. PMID- 2240180 TI - Malleus head fixation: association with pseudohypoparathyroidism. AB - Pseudohypoparathyroidism (PHP) is a heterogenous syndrome resulting from bone and renal resistance to parathyroid hormone (PTH). Hypocalcemia and hyperphosphatemia occur despite elevated PTH levels. Head and neck manifestations of PHP include tetany, laryngeal spasm, and ectopic calcification in the eye, dentition, subcutaneous tissue and brain. The first case of malleus head fixation caused by ectopic calcification in a PHP patient is reported. Normalization of serum calcium and phosphate levels does not appear to retard or correct this abnormality. Ossiculoplasty or amplification is currently the recommended treatment in PHP patients with malleus head fixation. PMID- 2240181 TI - Slowly progressive facial paralysis due to vascular malformation of the brain stem. AB - Slowly progressive facial paralysis is suggestive of a diagnosis other than Bell's palsy. A case of slowly progressive facial paralysis caused by a cavernous angioma of the brain stem is presented. The classification of vascular malformations of the central nervous system is described with emphasis on the MRI appearance of these lesions. PMID- 2240182 TI - 5-year-old with sudden facial paralysis. PMID- 2240183 TI - 45-year-old nondiabetic male with recurrent facial paralysis. PMID- 2240184 TI - Reanimation options for lower face in a patient post acoustic surgery. PMID- 2240185 TI - The deafness of Beethoven: an audiologic and medical overview. AB - The hearing loss of Ludwig von Beethoven has fascinated physicians, audiologists, and musicologists for almost 200 years. In this review of the literature, the features, treatment, and differential diagnosis of the composer's malady are discussed. An original series of hypothetical audiograms and actual photomicrographs depicting cochlear otosclerosis and Paget's disease are also provided. The author concludes with the majority of otologists that cochlear otosclerosis is the most likely diagnosis for the hearing loss. In addition, a summary of Beethoven's complicated medical history and results of the autopsy that confirmed chronic liver disease are included. PMID- 2240186 TI - Hearing loss--risk factor for cisplatin ototoxicity? Observations. AB - Ototoxicity associated with cisplatin chemotherapy is well established, but opinion is split regarding the relative risk associated with preexisting hearing loss. The emerging consensus is that pretreatment loss does not increase the risk of cisplatin ototoxicity. Results from a preliminary study of a small sample from our patient population supports this consensus. PMID- 2240187 TI - Thoughts on the management of chronic facial, head, and neck pain. AB - As previously stated in this paper, the therapeutic goal in the management of patients with chronic pain conditions in the face, head and neck is management and rehabilitation, striving for a 50 percent decrease in pain, a 50 percent increase in function and mobility, and a 50 percent decrease in medication with the elimination of agents with an addicting potential. These results will best be obtained through proper diagnosis and utilization of the aforementioned techniques in an interdisciplinary fashion as has been described. PMID- 2240189 TI - Private practice and paper writing: four suggestions to make both possible. PMID- 2240188 TI - A complex case of cochlear implant electrode placement. PMID- 2240191 TI - Sulfhydryls on frog skeletal muscle membrane participate in contraction. AB - To examine the molecular mechanism underlying contractile activation, we studied effects of a sulfhydryl reagent, N-(7-dimethylamino-4-methylcoumarinyl)maleimide (DACM), on twitch, Ag(+)-induced contraction, and K+ and caffeine contractures in single toe muscle fibers of frog. DACM suppressed twitch and Ag(+)-induced contraction, dose dependently, but not caffeine contracture. K+ contracture also was decreased appreciably by exposure to 40 microM DACM for 10 min. DACM elicited no shift of the mechanical threshold or inhibition of resting potential but slightly inhibited action potential. Increase of the fluorescence intensity produced by binding of 10 microM DACM to sulfhydryl groups was depressed by brief pretreatment with 100 microM Ag+. When exposed to 1 mM dithiothreitol (DTT) within 5 s of the rising phase of 5 microM Ag(+)-induced contraction, the fiber rapidly decreased the tension to the resting level. In this case, reapplication of 5 microM Ag+ after washing out DTT elicited a new contraction similar to the first Ag(+)-induced contraction. The second contraction amplitude depended on the time between the onset of the first Ag(+)-induced contraction and DTT application. If DTT was applied after more than 16 s, tension no longer developed on the second exposure to Ag+ or K+. The experiments provide evidence that crucial sulfhydryl groups participate in muscle activation. The possible role of the sulfhydryl group on the transverse tubular membrane in tension development is discussed. PMID- 2240190 TI - Platelet-activating factor and related acetylated lipids as potent biologically active cellular mediators. AB - Platelet-activating factor (PAF or 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is the most potent lipid mediator yet discovered. It is known to stimulate a wide span of biological responses ranging from aggregation and degranulation of platelets and neutrophils to a variety of cellular effects involving the stimulation of chemotaxis; chemokinesis; superoxide formation; protein phosphorylation; activation of protein kinase C, arachidonic acid, and phosphoinositide metabolites; glycogenolysis; and tumor necrosis factor production. Obviously, with such a diversity of biological activities, it is not surprising that PAF has been considered to be a key component in numerous diseases related to hypersensitivity and inflammatory responses. Evidence has also been presented for the role of PAF in physiological processes, particularly those involving reproduction and fetal development. Furthermore, because of its potent hypotensive action, PAF has been implicated as a contributing factor in blood pressure regulation. PAF is produced by two independent enzymatic pathways. The remodeling route involves the structural modification of a membrane lipid (1 alkyl-2-acyl-sn-glycero-3-phosphocholine) by replacement of the acyl moiety with an acetate group. An alternate route is the de novo synthesis of PAF from an O alkyl analogue of a lysophosphatidic acid that requires a reaction sequence of acetylation, dephosphorylation, and phosphocholine addition steps. Hypersensitivity and other pathophysiological reactions are thought to be caused by activation of the remodeling pathway, whereas the de novo route is believed to be the source of endogenous levels of PAF required for physiological functions. Inactivation of PAF occurs when the acetate group is hydrolyzed by an acetylhydrolase that is present in both extra- and intracellular compartments, although the catalytic activity of the two forms of acetylhydrolase are identical, some of their properties differ. The control of PAF metabolism is very complex, but acetylhydrolase, Ca2+, phosphorylation/dephosphorylation of enzymes, and fatty acids (especially polyunsaturates) appear to be important regulatory factors. Specific PAF receptors have clearly been demonstrated on several different types of cells, and although the mechanism of PAF actions is poorly understood, it appears that the PAF/receptor-induced responses are closely associated with the signal transduction process; both G proteins and adenyl cyclase appear to be involved. Because significant quantities of PAF are often retained within certain cells, the possibility of PAF serving as an intracellular mediator has also been proposed. PMID- 2240192 TI - Erythrocyte cation permeability induced by mechanical stress: a model for sickle cell cation loss. AB - Human red blood cells were subjected to mechanical shearing in a Couette viscometer at 37 degrees C, using polyvinylpyrrolidone to increase the medium viscosity. At stresses greater than 300 dyn/cm2, movement of both Na and K down their concentration gradients was observed. The net rate of both monovalent cation fluxes appeared to be linear with applied stress in the range of 300-910 dyn/cm2. The applied shear forces caused no fragmentation of the cells. Observed hemolysis was slight. The observed cation fluxes are not a result of hemolysis because the amount of K released by the hemolyzed cells is quantitatively inadequate to account for the net K efflux, and there is a net uptake of Na by the stressed erythrocytes, which cannot be a consequence of hemolysis. The rates of net Na uptake and K efflux were nearly equal (ratio = 0.93 +/- 0.40, n = 6). The stress-induced permeabilities were reversible when shearing was halted. This work demonstrates the existence of cation permeability inducible in the red cell membrane by mechanical deformation, which may be a model for the sickling-induced monovalent cation exchange observed in deoxygenated sickle cells. PMID- 2240193 TI - Pb2(+)-induced secretion from bovine chromaffin cells: fura-2 as a probe for Pb2+. AB - The effect of Pb2+ on catecholamine release was studied in isolated intact and permeabilized bovine chromaffin cells. Fura-2 was used to monitor intracellular Pb2+. A characterization of Pb2(+)-fura-2 interactions in solutions simulating intracellular ionic composition showed that Pb2+ forms a 1:1 Pb2(+)-fura-2 complex (apparent dissociation constant = 4.2 x 10(-12) M, pH 7.05) whose fluorescence resembles that of the Ca2(+)-fura-2 complex. Spectra recorded from fura-2-loaded cells indicate entry of Pb2+ into the cells. Intracellular Pb2+ concentrations were proportional to extracellular Pb2+ concentrations and were found to be 10(-11)-10(-12) M in cells exposed to micromolar Pb2+ concentrations. Pb2+ elicited the release of tritiated norepinephrine from fura-2-loaded cells, indicating the extraordinary effectiveness of Pb2+ as a releasing agent. Permeabilization of cells with digitonin showed that Pb2+ is able, in the absence of Ca2+, to produce exocytotic release at concentrations of 3.2 x 10(-10) M or higher (3 orders of magnitude lower than Ca2+). These results support the notion that Pb2+ can act as a potent Ca2+ surrogate in triggering secretion. PMID- 2240194 TI - Alteration in the myosin phosphorylation pattern of smooth muscle by phorbol ester. AB - Pretreatment with a high concentration of phorbol 12-myristate 13-acetate (PMA, 100 nM) increased the degree of tension and extent of myosin light chain (MLC20) phosphorylation in the K(+)-stimulated rabbit aortic artery. Pretreatment with 100 nM PMA did not alter the relationship between MLC20 phosphorylation and the tension seen with K+ stimulation in the initial phase and steady state of contraction. However, a low concentration of PMA (10 nM) potentiated only the MLC20 phosphorylation during the steady state of contraction with no effect on the tension. In contrast, the prostaglandin (PG) F2 alpha-induced tension development and the MLC20 phosphorylation were not affected by PMA pretreatment at both low and high concentrations. The inhibitory action of nifedipine on the K(+)-induced contraction was not affected by pretreatment with 100 nM PMA; the concentration producing half-maximal inhibition of nifedipine for the K(+) induced contraction (33 nM) was the same as that of the K+ plus 100 nM PMA induced contraction (32 nM). Our results suggest that PMA may increase the level of myosin light chain kinase-dependent MLC20 phosphorylation and the tension in the K(+)-stimulated artery, an effect which differs from that seen with increases in K+ concentrations. The regulatory mechanism for the contraction involving PGF2 alpha stimulation may differ from that seen in the case of K+ stimulation. PMID- 2240195 TI - Foreign anion substitution for chloride in human red blood cells: effect on ionic and osmotic equilibria. AB - In human red blood cells, when chloride was replaced isosmotically with a permeant chaotropic anion of the lyotropic series (NO3, I, or SCN), an immediate and significant loss of cell water was observed. In contrast, replacement of chloride by a substituted monovalent sulfonate, such as methanesulfonate or sulfamate, had no significant effect on cell water. Cell water loss in the presence of lyotropic anions was not the result of hemolysis or cation loss but was associated with a significant fall in the distribution ratios of protons (out/in) and chloride (in/out), suggesting an increase in nondiffusible intracellular negative charges. This hypothesis was examined using the equilibrium dialysis technique of Freedman and Hoffman (J. Gen. Physiol. 74: 157 185, 1979) in which fixed charges are titrated in cells permeabilized by nystatin. The equilibrium concentration ratios (in/out) of potassium, sodium, and chloride were determined at various external pH (pHo) values. The point at which anion and cation ratios are equal is the effective isoelectric point for the intracellular charges. In normal chloride-containing medium at 24 degrees C, this point was found at a pHo of 6.93. When chloride was replaced by a chaotropic anion, the isoelectric point at 24 degrees C shifted to a lower pHo: NO3 (6.38), I (5.98), and SCN (5.70). The substituted monovalent sulfonates had little effect on isoelectric point: methyl sulfate (6.81), sulfamate (7.00), and methanesulfonate (7.07). Calculation of the intracellular charges from titration data, as well as equilibrium distribution studies with [14C]SCN, suggests that lyotropic anion binding to intracellular sites (mainly hemoglobin) is responsible for the observed changes in cell water, cell pH, and chloride distribution. PMID- 2240196 TI - Role of polyamines in mitogenic and secretory responses of pancreatic beta-cells to growth factors. AB - We have investigated the effects of glucose and the polypeptide growth factor growth hormone (GH), platelet-derived growth factor (PDGF), insulin-like growth factor I (IGF-I), epidermal growth factor (EGF), and transforming growth factor alpha (TGF alpha) on the polyamine content, in relation to proliferation and insulin secretion and content, of pancreatic beta-cells. Fetal rat pancreatic islets containing a high proportion of beta-cells were cultured for 3 days with growth factors. beta-cell replication was significantly increased by glucose, GH, and PDGF plus IGF-I in parallel with increased islet polyamine contents. In contrast, neither EGF nor TGF alpha influenced the islet DNA synthesis rate, polyamine content, insulin content, or insulin accumulation in culture medium. When the increased polyamine content evoked by growth-promoting agents was prevented by inhibitors of polyamine synthesis, elevated DNA synthesis rates persisted or were even augmented. However, subcellular fractionation analysis of islet homogenates revealed that the nuclear polyamine content was not affected by the inhibitors. On the other hand, islet insulin content and glucose-regulated insulin release were decreased by polyamine synthesis inhibitors. Glucose oxidation rates remained unchanged, suggesting that inhibitors were not toxic to islet cells. We conclude that prevention of increases in total cellular content of polyamines in response to glucose, GH, or PDGF plus IGF-I does not prevent mitogenicity of these growth factors. However, when their synthesis is inhibited normal levels of polyamines seem to be maintained in the cell nucleus, an event that may be sufficient to permit a mitotic signal to be translated into a proliferative response. PMID- 2240197 TI - Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise. AB - Seven subjects cycled to fatigue [75 +/- 5 (SE) min] at a work load corresponding to approximately 75% of their maximal oxygen uptake. Biopsies were taken from the quadriceps femoris muscle at rest and during exercise. Muscle glycogen decreased from a preexercise level of 445 +/- 33 mmol glucosyl units/kg dry wt to 50 +/- 14 at fatigue. The sum of the measured tricarboxylic acid cycle intermediates (TCAI = malate + citrate + fumarate + oxaloacetate) was 0.49 +/- 0.05 mmol/kg dry wt at rest, increased to 4.41 +/- 0.23 after 5 min of exercise, and then decreased continuously to 3.33 +/- 0.29 and to 2.83 +/- 0.27 mmol/kg dry wt after 40 min of exercise and at fatigue (P less than 0.05 vs. 5 min), respectively. The point of fatigue was characterized by an enhanced deamination of AMP (judged by increase in IMP) and reduced contents (vs. 5 min of exercise) of lactate, pyruvate, and alanine. In contrast, acetylcarnitine (reflects the availability of acetylunits) increased threefold at the onset of exercise and was maintained approximately at this level until fatigue. It is concluded that prolonged exercise to fatigue at moderate work loads results in glycogen depletion, energy deficiency (increased AMP deamination), reduced levels of three-carbon compounds and TCAI (compared with the initial phase of exercise) but in maintained levels of acetylunits. The present data indicate that carbohydrate depletion may impair aerobic energy production by reducing the level of TCAI. PMID- 2240198 TI - Regulation of Cl- permeability in normal and cystic fibrosis sweat duct cells. AB - Reabsorptive cells of the human sweat gland normally exhibit a high basal Cl- permeability but are markedly impermeable to Cl- in cystic fibrosis (CF). We examined the possibility that the reduced basal Cl- permeability of CF sweat duct cells in primary culture is due to a defective regulation of plasma membrane Cl- permeability by prostaglandin E2 (PGE2), which is endogenously produced by cultured sweat duct cells. The macroscopic Cl- permeabilities of normal and CF sweat duct cells were assessed using a halide-specific fluorescent dye, 6-methoxy N-(3-sulfopropyl)quinolinium, in combination with fluorescence digital-imaging microscopy. The Cl- and Br- permeabilities of normal sweat duct cells were markedly reduced by inhibiting endogenous PGE2 production with indomethacin. This inhibition of Cl- permeability by indomethacin was largely reversed by the addition of PGE2 (10 nM to 1 microM), but not forskolin. Conversely, PGE2 failed to stimulate the low Cl- permeabilities of sweat duct cells cultured from CF subjects. Our results support the following conclusions: 1) a defective regulation of Cl- permeability in CF is a feature of reabsorptive as well as secretory epithelial cells, and 2) the nature of this regulatory defect extends beyond altered Cl- permeability regulation by adenosine 3',5'-cyclic monophosphate-dependent protein kinase. PMID- 2240199 TI - Glucose homeostasis and hypothalamic-pituitary-adrenocortical axis during development in rats. AB - Glucoprivation represents a model stress in which activation of different stress responses at different ages can be monitored both in vivo and in vitro. Physiological data indicate rat brain contains a liver/pancreas-type glucose sensor, yet no biochemical or immunocytochemical evidence exists for such a sensor. Young rats appear to lack normal hypothalamic glucose-sensing ability and do not show typical secretory patterns of corticotropin-releasing factor, adrenocorticotropic hormone, or corticosterone after experimentally induced glucoprivation. However, they hypersecrete catecholamines and glucagon (compared with adults) and thrive on fuel sources other than glucose that are abundant after birth. High steroid levels during the first 24 h after birth may be critical for inducing gluconeogenic enzymes and promoting differentiation of tissues like pancreas. Neonatal rats also have unique control systems to combat the damaging effects of other stresses like hypoxia; these systems may disappear in adults. Thus the definition of stress may change during development, and the compensatory mechanisms employed to combat stress change from neonatal to adult life and are intricately related to the metabolic needs of the animal. PMID- 2240200 TI - Fluxes and membrane transport of amino acids in rat liver under different protein diets. AB - The aim of the present work was to evaluate in vivo the role of the transport step in hepatic amino acid metabolism. To vary hepatic utilization of amino acids, rats were adapted to diets containing various concentrations of casein (5, 15, and 60%). In rats fed 5 or 15% casein diets, Gln and Glu were released by the liver, and there was a significant uptake of Ala. Hepatic fluxes of amino acids increased considerably after adaptation to high-casein diet (up to 1.55 mumol.min 1.g liver-1 for Ala), because of the rise in afferent concentrations as well as enhanced uptake percentage (peaking at 60-75% for most glucogenic amino acids). Adaptation to a high-protein diet led to induction of not only system A but also of most of the other transport systems (Gly, anionic, T, y+, and to a lesser extent system N); only systems ASC and L were unchanged. The study of amino acid repartition between liver and plasma with different diets indicates that transport could modulate utilization of Ala, Ser, Thr, Gly, Gln, and Asp. For Arg and Asn, present in very low concentrations in liver under any condition, the transport step should be the major locus of control of their metabolism. For amino acids chiefly transported by nonconcentrative systems, such as aromatic amino acids, cellular metabolism could also be limited by the transport process. In conclusion, during adaptation to a high-protein diet, there is apparently a coordinated adaptation of amino acid transport and of their intracellular metabolism. For some amino acids, induction of catabolic enzymes seems greater than that of transport, so that the transport step may play an important role in control of metabolic fluxes. For example, concentration of amino acids such as Thr may be markedly depressed in rats adapted to a high-protein diet. PMID- 2240201 TI - Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects. AB - We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with [2-3H]glucose and HGP with [6-3H]glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). [2-3H]- minus [6 3H]glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6 phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP. PMID- 2240202 TI - Effect of two methods of hand heating on body temperature, forearm blood flow, and deep venous oxygen saturation. AB - Two methods of hand heating [warmed blanket 40 degrees C (WB) and warm-air box 55 degrees C (WA)] were compared with the effect of no heating (control) in six healthy females. After 30 min baseline, the left hand was either heated for 1 h or not heated. Measurements were made of skin temperature (ST), core temperature (CT), right forearm (FBF) and skin blood flow (SBF), and right forearm deep venous blood oxygen content with and without occlusion of the hand circulation. CT rose above baseline in WB (by +0.2 degrees C, P less than 0.01) but not with control or WA. Abdominal ST rose only with WB (by +0.66 degrees C above baseline, P less than 0.01). FBF increased above baseline values with both WA (by +10 ml.l forearm-1.min-1) and WB (by +12 ml.l forearm-1.min-1), but neither was significantly greater than the control. SBF increased above baseline only with WB (by +202 mV, P less than 0.01), and this was significantly greater than control SBF. With an occluded hand circulation, deep venous oxygen content rose above baseline values with WB only (+6.0%, P less than 0.01) but was not greater than control with either method of hand heating. We conclude that using a warm-air box has less effect than a heated blanket on the measured variables. PMID- 2240204 TI - Role of corticosterone in adaptive changes in energy expenditure during refeeding after low calorie intake. AB - We examined the importance of corticosterone in elevated efficiency of energy utilization during refeeding after low food consumption. Energy balance studies during refeeding (over periods of 14 or 16 days) were conducted in rats previously food restricted for 16 days at 50% of normal food intake. Comparisons made with nonrestricted weight-matched controls after validation studies indicated that 2-wk-younger weight-matched controls had similar maintenance energy requirements and similar efficiency of energy utilization above maintenance (i.e., net efficiency) to nonrestricted age-matched controls. Results indicate that relative to controls refeeding after low food consumption was associated with enhanced energy conservation underlain by a 16-18% reduction (P less than 0.001) in total energy expenditure over a 14-day period. This metabolic adaptation for energy conservation resulted in a threefold increase (P less than 0.001) in body fat accretion but no difference in body protein deposition. Bilateral adrenalectomy (ADX) 2 days before refeeding reduced differences in energy expenditure between refed group and controls from 18 to 8% (P less than 0.01) and attenuated body fat gain from a three- to twofold increase (P less than 0.001) above control group. Effects of ADX were prevented by daily corticosterone replacement. Data suggest that after a period of low calorie intake an adaptive neurohormonal switching mechanism facilitates replenishment of fat stores during refeeding. This metabolic reorientation (characterized by an adaptive fall in energy expenditure) has both an adrenal as well as a nonadrenal component, because it is partially reversed by prior bilateral ADX, an effect attributed to removal of corticosterone-induced inhibition of thermogenesis. PMID- 2240203 TI - Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ. AB - Reduced oxidation of fat leading to a positive fat balance could be a factor in the development of obesity. Twenty-four-hour respiratory quotient (RQ) was measured in 152 nondiabetic Pima Indians fed a weight-maintenance diet [87 males and 65 females; 27 +/- 6 yr (mean +/- SD); 93.9 +/- 22.9 kg; 32 +/- 9% fat]. Twenty-four-hour RQ varied from 0.799 to 0.903. Prior change in body weight, 24-h energy balance, sex, and percent body fat explained 18% of the variance in 24-h RQ (P less than 0.001). In a subgroup of 66 siblings from 28 families, family membership explained 28% of the remaining variance in 24-h RQ (P less than 0.05). In 111 subjects for whom follow-up data (25 +/- 11 mo) were available, 24-h RQ was correlated with subsequent changes in body weight and fat mass (r = 0.27, P less than 0.01 and r = 0.19, P less than 0.05, respectively). Subjects with higher 24-h RQ (90th percentile) independent of 24-h energy expenditure were at 2.5 times higher risk of gaining greater than or equal to 5 kg body weight than those with lower 24-h RQ (10th percentile). We conclude that in Pima Indians fed a standard diet 1) family membership is the principal determinant of the ratio of fat to carbohydrate oxidation, and 2) a low ratio of fat to carbohydrate oxidation is associated with subsequent weight gain independent of low energy expenditure and may contribute to the familial aggregation of obesity. PMID- 2240205 TI - Regulation of serum 1,25-dihydroxyvitamin D3 in lactating rats. AB - To characterize further the mechanism(s) underlying the increased serum 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] concentration associated with lactation in the rat, we examined hormone biosynthesis [i.e., renal 25-hydroxyvitamin D-1 alpha hydroxylase (1 alpha-hydroxylase) activity] and hormone disappearance in groups of lactating Holtzman rats and age- and sex-matched nonlactating controls. 1 alpha-Hydroxylase activity was significantly greater in kidneys from lactating rats (4.0 +/- 0.42 fmol.mg-1.min-1) on a basal diet than in those from nonmated females (1.4 +/- 0.08 fmol.mg-1.min-1), an increment sufficient to account for the observed fourfold elevation of 1,25(OH)2D3 in the dams. The increase occurs despite the lower serum 1,25(OH)2D3 levels in lactating than in nonlactating rats at 12 and 24 h after a bolus injection of 1,25(OH)2D3 (2 ng/g body wt). Elevation of serum 1,25(OH)2D3 is not a requisite consequence of lactation, however, because dams receiving supplemental calcium from food (1.6%) and water (0.3%) exhibited no increase of either serum 1,25(OH)2D3 or 1 alpha-hydroxylase activity compared with controls. In contrast, lactating rats that received a diet with only 0.1% calcium had 5-fold higher serum 1,25(OH)2D3 levels and 20-fold higher 1 alpha-hydroxylase activity than nonlactating rats on the same diet. We conclude that other factors in conjunction with lactation, but not the lactating state per se, promote the changes in 1,25(OH)2D3 metabolism observed. PMID- 2240206 TI - Contribution of liver and skeletal muscle to alanine and lactate metabolism in humans. AB - To quantitate alanine and lactate gluconeogenesis in postabsorptive humans and to test the hypothesis that muscle is the principal source of these precursors, we infused normal volunteers with [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose and calculated alanine and lactate incorporation into plasma glucose corrected for tricarboxylic acid cycle carbon exchange, the systemic appearance of these substrates, and their forearm fractional extraction, uptake, and release. Forearm alanine and lactate fractional extraction averaged 37 +/- 3 and 27 +/- 2%, respectively; muscle alanine release (2.94 +/- 0.27 mumol.kg body wt-1.min-1) accounted for approximately 70% of its systemic appearance (4.18 +/- 0.31 mumol.kg body wt-1.min-1); muscle lactate release (5.51 +/- 0.42 mumol.kg body wt 1.min-1) accounted for approximately 40% of its systemic appearance (12.66 +/- 0.77 mumol.kg body wt-1.min-1); muscle alanine and lactate uptake (1.60 +/- 0.7 and 3.29 +/- 0.36 mumol.kg body wt-1.min-1, respectively) accounted for approximately 30% of their overall disappearance from plasma, whereas alanine and lactate incorporation into plasma glucose (1.83 +/- 0.20 and 4.24 +/- 0.44 mumol.kg body wt-1.min-1, respectively) accounted for approximately 50% of their disappearance from plasma. We therefore conclude that muscle is the major source of plasma alanine and lactate in postabsorptive humans and that factors regulating their release from muscle may thus exert an important influence on hepatic gluconeogenesis. PMID- 2240207 TI - Reversal of enhanced muscle glucose transport after exercise: roles of insulin and glucose. AB - Exercise stimulates insulin-independent glucose transport in skeletal muscle and also increases the sensitivity of the glucose transport process in muscle to insulin. A previous study [D. A. Young, H. Wallberg-Henriksson, M. D. Sleeper, and J. O. Holloszy. Am. J. Physiol. 253 (Endocrinol. Metab. 16): E331-E335, 1987] showed that the exercise-induced increase in glucose transport activity disappears rapidly when rat epitrochlearis muscles are incubated for 3 h in vitro in the absence of insulin and that 7.5 microU/ml insulin in the incubation medium apparently slowed the loss of enhanced sugar transport. We examined whether addition of insulin several hours after exercise increases glucose transport to the same extent as continuous insulin exposure. Addition of 7.5 microU/ml insulin 2.5 h after exercise (when glucose transport has returned to basal levels) increased sugar transport to the same level as that which resulted from continuous insulin exposure. This finding provides evidence for an increase in insulin sensitivity rather than a slowing of reversal of the exercise-induced increase in insulin-independent glucose transport activity. Glucose transport was enhanced only at submaximal, not at maximal, insulin concentrations. Exposure to a high concentration of glucose and a low insulin concentration reduced the exercise-induced increase in insulin-sensitive glucose transport. Incubation with a high concentration of 2-deoxy-D-glucose (2-DG) did not alter the increase in insulin sensitivity, even though a large amount of 2-DG entered the muscle and was phosphorylated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240208 TI - Food deprivation alters liver glycogen metabolism and endocrine responses to hemorrhage. AB - Liver glycogen content, blood glucose, insulin, glucagon, and epinephrine were determined during 1 h hemorrhagic hypotension at 60 mmHg and 23 h thereafter in fed and two groups of 24-h food-deprived rats receiving either no infusion or 30% glucose intravenously during hemorrhage. Liver glycogen content was reduced by greater than 90% after 24-h food deprivation. Fed and food-deprived rats given glucose developed similar and substantial elevations of blood glucose during hemorrhage, whereas changes in blood glucose were modest in food-deprived rats given no infusion. In fed rats, liver glycogen was reduced by 60% during the 1-h bleed, but within 2 h after hemorrhage repletion of liver glycogen content commenced. By 6 h, approximately 75% of the glycogen lost during hemorrhage had been restored, and 23 h after hemorrhage liver glycogen content was six times greater compared with nonbled controls. Although glycogen levels increased after hemorrhage in food-deprived animals, the increase was negligible compared with that found in fed rats. Infusion of glucose during hemorrhage or adrenergic blockade after hemorrhage did not alter glycogen repletion in food-deprived rats. Posthemorrhage fed animals had high levels of insulin, glucagon, and epinephrine during hemorrhage, whereas insulin levels remained low in food-deprived rats despite exogenously induced hyperglycemia. It is concluded that rapid and substantial glycogen repletion can occur even immediately poststress. The conditions seem to be related to the nutritional state at the time of the insult. PMID- 2240209 TI - Insulin- and thyroid hormone-independent adaptation of myofibrillar proteolysis to glucocorticoids. AB - Myofibrillar protein breakdown in skeletal muscle progresses through two distinct phases in response to chronic glucocorticoid administration in the rat, i.e., an early phase lasting 4-5 days, during which proteolysis increases followed by a later phase during which proteolysis decreases. The possible involvement of insulin and the iodothyronines in this phenomenon has now been examined. Diabetic, thyroidectomized, and normal rats were treated with corticosteroid for 10-11 days, and at timed intervals muscle proteolysis was evaluated by measuring the release of 3-methyl-L-histidine (3-MH) and tyrosine from the perfused hindquarter as well as the excretion of 3-MH in the urine. Corticosterone (CTC) administration to normal rats increased plasma insulin, whereas plasma 3,5,3' triiodothyronine responded with an early rise followed by a fall after 4-5 days. However, the biphasic response of myofibrillar proteolysis to chronic glucocorticoid treatment was not abolished in CTC-treated diabetic or thyroidectomized rats. CTC treatment increased release of tyrosine by perfused muscle of diabetic rats but, unlike 3-MH release, did not diminish later. Thus the adaptation of myofibrillar proteolysis to chronic glucocorticoid treatment appears to be independent of insulin and thyroid hormones. However, insulin may play a role in curtailing glucocorticoid-induced breakdown of nonmyofibrillar proteins. PMID- 2240210 TI - Different responses of trabecular and cortical bone to 1,25(OH)2D3 infusion. AB - Previous studies regarding the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on bone have suggested that 1,25(OH)2D3 increases bone mass and calcium. Many of these studies have focused on trabecular or total bone without examining cortical bone per se. To determine whether the response of trabecular bone to 1,25(OH)2D3 differed from the response of cortical bone, we infused 1,25(OH)2D3 into rats and examined bone mass, 45Ca accumulation, and the density distribution of bone particles (as a measure of bone maturation) in both the proximal tibia and shaft. In the proximal tibia 1,25(OH)2D3 decreased 45Ca accumulation, yet increased bone mass and shifted the particle distribution to more mineralized fractions. In the shaft there was a redistribution of bone to less mineralized fractions that was not accompanied by a change in total bone mass or a decrease in 45Ca accumulation. Thus 1,25(OH)2D3 may retard bone maturation and mineralization throughout the tibia, but this effect in the proximal tibia appears to be overshadowed by a reduction in bone resorption resulting in an accumulation of well-mineralized bone in that region. Bone resorption, however, was not measured directly. The net result is an increase in bone mass and density of trabecular bone not seen in cortical bone. PMID- 2240211 TI - Dose-dependent effect of insulin on plasma free fatty acid turnover and oxidation in humans. AB - Methodology for measuring plasma free fatty acid (FFA) turnover/oxidation with [1 14C]palmitate was tested in normal subjects. In study 1, two different approaches (720-min tracer infusion without prime vs. 150-min infusion with NaH14CO3 prime) to achieve steady-state conditions of 14CO2 yielded equivalent rates of plasma FFA turnover/oxidation. In study 2, during staircase NaH14CO3 infusion, calculated rates of 14CO2 appearance agreed closely with NaH14CO3 infusion rates. In study 3, 300-min euglycemic insulin clamp documented that full biological effect of insulin on plasma FFA turnover/oxidation was established within 60-120 min. In study 4, plasma insulin concentration was raised to 14 +/- 2, 23 +/- 2, 38 +/- 2, 72 +/- 5, and 215 +/- 10 microU/ml. A dose-dependent insulin suppression of plasma FFA turnover/oxidation was observed. Plasma FFA concentration correlated positively with plasma FFA turnover/oxidation in basal and insulinized states. Total lipid oxidation (indirect calorimetry) was significantly higher than plasma FFA oxidation in the basal state, suggesting that intracellular lipid stores contributed to whole body lipid oxidation. Hepatic glucose production and total glucose disposal showed the expected dose dependent suppression and stimulation, respectively, by insulin. In conclusion, insulin regulation of plasma FFA turnover/oxidation is maximally manifest at low physiological plasma insulin concentrations, and in the basal state a significant contribution to whole body lipid oxidation originates from lipid pool(s) that are different from plasma FFA. PMID- 2240212 TI - Interpretation of isotopomer patterns in tracing glycogen synthesis and glucose recycling using [13C6]glucose. AB - Tracing glycogen synthesis with [U-13C]glucose involves determination of isotopomer patterns in precursors and products. The contribution of the direct pathway to glycogen synthesis has been estimated from the ratio (R) of the number of glycogen glucose molecules having six 13C atoms to the total number of glucose molecules having one to six 13C atoms. Using theoretical examples, we show that the equation to calculate R underestimates the contribution of the direct pathway. We derive a correct stoichiometric expression for R. Also, we show how to correct these estimates for 1) recondensation of two M+3 three-carbon intermediates into M+6 glucose 6-phosphate, and 2) the increasing enrichment of arterial glucose in various isotopomers arising from the indirect pathway. Finally, using the developed formulas we recalculate data from the literature. Similar considerations apply to investigations of glucose recycling using [U 13C6]glucose. PMID- 2240213 TI - Effect of T. spiralis infection on intestinal motor activity in the fasted state. AB - We sought to determine the effects of Trichinella spiralis infection on small intestinal motor activity in the fasted state in dogs and relate it to clinical symptoms during the intestinal phase of trichinosis. Motor activity was recorded by strain gauge force transducers. Infection with T. spiralis resulted in a significant increase in the incidence and proximal origination of giant migrating contractions (GMCs) during the first 5 days postinfection. This was also the time when the dogs had diarrhea. The dogs were often restless and showed signs of discomfort during proximally originating GMCs. The incidence of retrograde giant contractions (RGCs) increased significantly on the 2nd and 3rd day postinfection. RGCs were followed by vomiting 71% of the time during infection. The migrating motor complex cycle length increased significantly, and this was due to intestinal "amyogenesia" and "dysmyogenesia". During these phenomena, electrical control activity was almost completely obliterated in the proximal half of the small intestine (amyogenesia) and became irregular and unstable in the distal half (dysmyogenesia). Intestinal amyogenesia and dysmyogenesia lasted up to 4 h and were terminated by a GMC. We conclude that diarrhea induced by T. spiralis infection is closely associated with an increase in the incidence and proximal origin of GMCs. These GMCs may also be the motor correlates of abdominal cramping and pain during the intestinal phase of trichinosis. PMID- 2240214 TI - Relationship between maternal milk PGE2 and gastric acid secretion in newborn rats. AB - We previously demonstrated that in rats gastric acid secretion declines after birth and drops steeply on day 12 of life. In the present study, we investigated the part played in this decline by prostaglandin E2 (PGE2) from maternal milk. PGE2 content was first measured in the milk of untreated dams 0, 1, 5, 10, 12, 15, and 18 days after parturition. PGE2 levels were high during the first 5 days (123.5-200.5 pg/ml), declined significantly between days 10 and 15 (56.6-85.4 pg/ml; P less than 0.05), and dropped to 18.4 pg/ml on day 18. We also found that depleting milk of PGE2 prevented drop of acid secretion in 12-day-old suckling rats. Injecting lactating dams with indomethacin significantly reduced milk PGE2 content by 65% vs. milk of untreated dams. Surprisingly, administration of sesame oil, the indomethacin vehicle to the dams, increased milk PGE2 content by 182%. In the pups of the indomethacin-treated dams, acid secretion did not drop. On the contrary, in vivo basal and histamine-induced acid output rose markedly by 40 and 50%, respectively, and in vitro the net movements of 36Cl and 22Na measured in the isolated stomach indicated that active Cl- secretion had resumed. Mucosal PGE2 did not appear to be significantly involved in early development of acid secretion because administration of indomethacin to pups from untreated dams did not significantly modify the secretion measured on day 12. Data indicate that maternal milk depletion of PGE2 prevents the drop of gastric acid secretion previously observed in 12-day-old pups and suggest that in infant rats maternal PGE2 plays a physiological part in regulating acid secretion. PMID- 2240216 TI - Comparison of calcium and magnesium absorption: in vivo and in vitro studies. AB - Transport characteristics of Ca and Mg were compared at three different levels of the absorptive process in male (120-170 g) Wistar rats. Balance studies in intact rats revealed that fractional Ca absorption decreased with increased Ca intake so that net Ca absorption remained constant. Fractional Mg absorption decreased modestly with increased Mg intake so that net Mg absorption increased proportionately with increased dietary Mg. Everted duodenal sacs demonstrated the presence of active Ca absorption with serosal-to-mucosal (S/M) ratio of 2.65 +/- 0.20 (n = 6), which was greater than unity (P less than 0.001). In contrast, the S/M for Mg did not exceed unity. Mucosal duodenal Ca uptake exhibited a large saturable (Michaelis constant of 4.80 +/- 0.34 mM, maximal velocity of 4.71 +/- 0.13 nmol.min-1.mg-1) and a small nonsaturable component (0.12 +/- 0.01 nmol.min 1.mg-1) in 5-wk-old rats (120 g). In 72-wk-old rats (600 g) the diffusional component of Ca uptake became predominant, and the slope increased significantly to 0.32 +/- 0.01 (P less than 0.05). Duodenal Mg uptake was completely concentration dependent and exhibited no age-related changes. PMID- 2240217 TI - Fasting and postprandial hepatic bile flow in unanesthetized opossums. AB - In conscious opossums, we evaluated the relationship between hepatic bile flow and the intestinal motor function during fasting as well as after feeding. In six opossums, bipolar electrodes were implanted from the gastric antrum to the terminal ileum. After cholecystectomy, the common duct was ligated, and a catheter was tied into the proximal common duct for collecting hepatic bile. During subsequent studies, hepatic bile flow was measured, and bile was returned to the duodenum through an externalized duodenal catheter. Cyclic increases in bile flow during fasting did not show a close correlate with the duodenal migratory motor complex (MMC) cycle. Rather, bile flow showed peak values [0.11 +/- 0.02 (SE) ml/min] when phase III MMC activity reached the midileum. Hepatic bile flow correlated closely with the amount of bile acid secreted by the liver. When the bile acid pool was depleted by diverting bile from the intestine, hepatic secretion of bile fell to uniformly low values of approximately 0.04 ml/min that did not show cyclic variation. Hepatic bile flow after feeding increased to a maximal value of 0.12 +/- 0.01 ml/min at 90 min. We conclude that increases in hepatic bile flow during fasting and after meals are determined mainly by variations in intestinal motor activity that alter small bowel transit and thereby affect the enterohepatic circulation of bile acids. PMID- 2240215 TI - Fat feeding increases size, but not number, of chylomicrons produced by small intestine. AB - To test the regulatory effect of dietary triglyceride (TG) on rat lymphatic apolipoprotein B (apo B) transport, lymph-fistula rats were infused intraduodenally for 8 h at 3 ml/h with a lipid emulsion containing 40 mumol TG labeled with glycerol [9,10-3H(N)]triolein, 7.8 mumol egg phosphatidylcholine, and 57 mumol sodium taurocholate in phosphate-buffered saline with or without 1 mg/h Pluronic L81 (L81). L81 is known to prevent lipid transport in the intestine by inhibiting the formation of chylomicrons (CM). This action of L81 is quickly reversible by merely replacing L81 infusion by saline infusion. In the control rats (without L81 added to the infusate), the amount of apo B secreted in either whole lymph, CM, or the very-low-density lipoprotein (VLDL) fractions did not change significantly during lipid infusion compared with fasting. Compared with the fasting, the apo B output in lymph during L81 plus lipid or saline infusion in the experimental rats did not change significantly. The lymphatic apo B output data were also supported by the incorporation studies using [3H]leucine. In summary, these data demonstrate that the absorption of a physiological load of lipid into lymph does not affect the apo B synthesis in the mucosa or the secretion of apo B in lymph. Furthermore, the action of L81 is probably not by inhibiting intestinal apo B production because apo B secretion was not affected by the presence of L81. This study also demonstrates that the number of CM particles made by the small intestine remains relatively constant during fasting or active lipid uptake and transport. During active lipid absorption, instead of increasing the number of CM, the enterocytes expand the size of the CM particles. Lastly, the number and TG content of VLDL particles synthesized and secreted by the small intestine also seems to remain relatively constant during fasting and active lipid absorption. PMID- 2240218 TI - Leukotriene D4 excitation of rabbit distal colon arises in the region of the muscularis mucosae. AB - We previously have demonstrated in vivo that intra-arterial administration of leukotriene D4 (LTD4) causes increased myoelectric and mechanical activity in the rabbit distal colon. The aim of this study was to use both in vivo and in vitro techniques to try to elucidate the mechanism underlying this effect. In vivo the excitatory response of the rabbit distal colon to LTD4 was abolished by pretreatment with atropine (0.1 mg/kg iv) or hexamethonium (5 mg/kg iv) or the LTD4 receptor antagonist SK&F 102922 (0.8 micrograms/kg ia). In vitro neither the longitudinal nor the circular muscle layer responded to LTD4 (10(-10) to 10(-7) M) with a contractile response. Over the same concentration range, LTD4 caused contractions of the muscularis mucosae that were attenuated by either SK&F 102922 (10(-9) to 10(-7) M) or indomethacin (10(-6) M) but were unaffected by atropine (10(-6) M), pyrilamine (10(-6) M), or tetrodotoxin (10(-6) M). Full thickness segments of longitudinal muscle, circular muscle, and muscularis mucosae did not contract to LTD4. These data imply that LTD4-induced excitation of the rabbit distal colon in vivo arises as a result of the excitation of LTD4 receptors in the region of the muscularis mucosae and that this leads ultimately to the release of acetylcholine onto the muscularis propria. It is proposed that one possible mechanism leading to the latter effect is an increased excitability of intrinsic nerves resulting from a prostaglandin-induced depression of norepinephrine release from nerves impinging on the submucosal plexus. PMID- 2240219 TI - Glycyl-L-sarcosine transport by ATP-depleted isolated enterocytes from chicks. AB - Normally energized and ATP-depleted isolated chicken enterocytes have been used to investigate the energetics of intestinal glycyl-L-sarcosine (Gly-Sar) transport, and the results were compared with those obtained for 3-O-methyl-D glucose (3-OMG) active transport, which is known to be energized by the electrochemical Na+ gradient. The results show that even though Gly-Sar had no effect on Na+ efflux from labeled (22Na) enterocytes, 20 mM L-leucine and 20 mM 3 OMG increased the rate constant of Na+ efflux by 34 and 76%, respectively. In ATP depleted cells 3-OMG was accumulated in response to experimentally imposed inward Na+ gradients; however, Gly-Sar was not accumulated. In the absence of Na+, an inward proton gradient slightly increased Gly-Sar uptake, although no transient accumulation was observed. An increase in membrane potential by replacement of Cl by NO3- or by imposition of an outward K+ gradient in the presence of valinomycin stimulated both 3-OMG and Gly-Sar uptake, even in the absence of either H+ or Na+ gradient. When in addition to a K+ diffusion potential, a Na+ gradient was present, 3-OMG transient accumulation was further increased (approximately 2-fold over equilibrium value), and Gly-Sar uptake showed the same pattern as that observed when only membrane potential was present. However, in the presence of an outward K+ diffusion potential and an inward H+ gradient Gly Sar was stimulated approximately threefold, clearly showing a significant overshoot, whereas 3-OMG was not transiently accumulated. PMID- 2240220 TI - Evaluation of selective liver denervation methods. AB - This study compares four methods of hepatic denervation and defines the rate and physiological significance of reinnervation. Five groups of rats were prepared: 10 underwent orthotopic liver transplantation. In nine rats a 90% aqueous phenol solution was applied circumferentially to the portal vein. Thirteen rats underwent microsurgical denervation; 28 received different doses of 6 hydroxydopamine (6-HODA) administered as a single intraportal injection [50 (n = 10), 75 (n = 6), and 100 mg/kg (n = 6)]. Twelve rats were studied as controls. Rats were killed 1, 4, and 8 wk after surgery to determine liver tissue content of norepinephrine (NE). Changes in mean arterial pressure (MAP) in response to hepatic nerve stimulation, which was supramaximum in intensity and frequency, were measured before rats were killed. NE content in controls ranged from 121 to 204 ng/g and MAP increased by 30-38 mmHg after electrical stimulation. At 1, 4, and 8 wk after treatment the liver NE content was less than 1, 2.3, and 20.2 ng/g in the transplant group; less than 1, 2.7, 4.1 ng/g in the phenol group; and 17.2, less than 1, and 3 ng/g in the surgically denervated group. In the 6-HODA group, values were 18.9, 47, and 61.5 ng/g (50 mg/kg); 5.7, 20.2, and 15 ng/g (75 mg/kg); and 7.7, 2.5, and 17.5 ng/g (100 mg/kg). When the level of NE was undetectable, MAP increase after stimulation was 0-18% that of controls. When NE content was 15-23% of normal, MAP increased 49-62% regardless of the denervation technique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240221 TI - Water and ion handling in the rat cecum. AB - The minute-by-minute net water movement (Jw) in the rat cecum was correlated with the transepithelial potential difference (PD), short-circuit current (Isc), and the unidirectional Na+, Cl-, and Rb+ fluxes, with the following results. 1) Jw was a linear function of the applied hydrostatic or osmotic transepithelial gradients (hydrostatic permeability coefficiency = 0.164 +/- 0.018 cm/s, n = 13; osmotic permeability coefficient = 0.0014 +/- 0.0002 cm/s, n = 6). 2) A fraction of this absorptive Jw (0.17 +/- 0.03 microliter.min-1.cm-2, n = 13) was independent of the presence of any osmotic, hydrostatic, or chemical gradient. 3) This fraction was Na+ dependent, associated with an amiloride-insensitive PD and net Na+ (2.37 +/- 0.68 mu eq.h-1.cm-2, n = 6) and Cl- influxes (3.45 +/- 1.46 mu eq.h-1.cm-2, n = 6), measured under short-circuit conditions. No net Rb+ movement was detected. 4) The absorptive Jw increased when HCO3- was replaced by tris(hydroxymethyl)aminomethane (Tris+) buffer or Cl- by SO4(2-). A good agreement between the observed and the expected Jw (assuming isosmotic reabsorption) was observed in the absence of HCO3-. 5) The presence of an osmotic but not a hydrostatic transepithelial gradient generated a transepithelial PD. These results show that water movement across the rat cecum in vitro is the result of a combination of hydrostatic-, osmotic-, and transport-associated transfers. Concerning this last driving force, the observed results indicate that the transport-related Jw results from the addition of an absorptive Jw, coupled to a nonelectrogenic NaCl entry, plus a secretory Jw probably coupled to HCO3- secretion. PMID- 2240222 TI - Sulfate and oxalate exchange for bicarbonate across the basolateral membrane of rabbit ileum. AB - The purpose of these studies was to further define the transport of SO4(2-) and oxalate across the basolateral membrane (BLM) of rabbit ileum. We previously found evidence for Cl-(-)SO4(2-) exchange but no evidence for carrier-mediated oxalate transport. A HCO3- gradient (but not a pH gradient) was found to stimulate SO4(2-) and oxalate uptake in BLM vesicles; uptake was inhibited by DIDS. Oxalate cis-inhibited HCO3- gradient SO4(2-) uptake and trans-stimulated SO4(2-) uptake, suggesting SO4(2-) and oxalate used the same carrier (SO4(2-)- and oxalate-HCO3-exchange). Cl- had no effect on HCO3- gradient-stimulated SO4(2 ) uptake, indicating that Cl(-)-SO4(2-) exchange was a different carrier. Other substrates found to be transported on the HCO3- exchanger were oxaloacetate and S2O3(2-)-.SO4(2-), S2O3(2-). and oxalate were found to also use the SO4(2-)-Cl- exchanger, whereas oxalate was only transported on the HCO3- exchanger. SO4(2-) HCO3- exchange was found on villus, but not crypt cell, BLM. These results indicate that there is a SO4(2-)-HCO3- exchanger on the BLM of villus cells that also transports oxalate, and along with our previous studies, the results provide evidence for the transepithelial transport of oxalate. PMID- 2240223 TI - Phagocytosis by Kupffer cells predominates in pericentral regions of the liver lobule. AB - These studies were designed to determine whether particle phagocytosis could be monitored from the surface of the perfused liver. To achieve this goal, decreases in reflected light were measured during phagocytosis of colloidal carbon particles. Livers were illuminated with 623-nm light via a relatively large fiber optic light guide (tip diam 2 mm), and reflected light was monitored continuously. A decrease in reflected light was observed when carbon was infused that was proportional to the influent carbon concentration. Initial changes in reflected light were linearly related to rates of carbon uptake by Kupffer cells. Subsequently, rates of carbon uptake were determined from changes in reflected light in periportal and pericentral regions of the liver lobule with miniature fiber-optic light guides. In perfusions in the anterograde direction, rates of carbon uptake were approximately 80% higher in pericentral than periportal regions of the liver lobule. This pattern was reversed when livers were perfused in the retrograde direction. Thus particle phagocytosis predominates in downstream regions of the liver lobule. Because decreasing the pH of the influent perfusate increased carbon uptake, the pH gradient over the liver lobule may be involved in the regulation of particle uptake at the sublobular level. PMID- 2240224 TI - Luminal glucose concentrations in the gut under normal conditions. AB - Luminal glucose (Glc) concentrations in the small intestine (SI) are widely assumed to be 50-500 mM. These values have posed problems for interpreting SI luminal osmolality and absorptive capacity, Glc transporter Michaelis-Menten constants (Km), and the physiological role of active Glc transport and its regulation. Hence we measured luminal contents, osmolality, and Glc, Na+, and K+ concentrations in normally feeding rats, rabbits, and dogs. Measured Glc concentrations were compatible with the portion of measured osmolality not accounted for by Na+ and K+ salts, amino acids, and peptides. Mean SI luminal osmolalities were less than or equal to 100 mosmol/kg hypertonic. For animals on the most nearly physiological diets, SI Glc concentrations averaged 0.4-24 mM and ranged with time and SI region from 0.2 to a maximum of 48 mM. The older published very high values are artifacts of direct infusion of concentrated Glc solutions into the gut, nonspecific Glc assays, and failure to test for quantitative recovery or to centrifuge samples in the cold. By storing food after meals and releasing it between meals, rat stomach greatly damps diurnal fluctuations in quantity and osmolality of food reaching the SI and hence also damps fluctuations in absorption rates. These new values for luminal Glc have five important physiological implications: the problem of accounting for apparently very hypertonic SI contents in the face of high osmotic water permeability disappears; the effective Km of the SI Glc transporter is now comparable to prevailing Glc concentrations; the SI no longer appears to have enormous excess absorptive capacity for Glc; regulation of Glc transport by dietary intake now makes functional sense; and the claim that high luminal Glc concentrations permit solvent drag to become the major mode of Glc absorption under normal conditions is undermined. PMID- 2240225 TI - Modulation of PAF-induced leukocyte adherence and increased microvascular permeability. AB - The objective of this study was to assess whether superoxide and leukocyte adhesion glycoproteins (CD18) mediate the leukocyte adherence to mesenteric microvessels and increased intestinal microvascular permeability induced by platelet-activating factor (PAF). PAF was infused into the arterial supply of an isolated autoperfused segment of cat intestine. Thirty minutes into the infusion, the number of adherent leukocytes within mesenteric venules was measured. This was followed by intravenous administration of either human recombinant superoxide dismutase (hSOD), hydrogen peroxide-inactivated hSOD, or a monoclonal antibody against the leukocyte adhesion molecule CD18 (MoAb IB4), and 30 min later, adherence measurements were repeated. hSOD and MoAb IB4 produced a 30 and 66% decrease, respectively, in leukocyte adherence, whereas inactivated hSOD had no effect. Adherence of PAF-activated cat neutrophils to plastic was reduced only by MoAb IB4, suggesting that PAF-induced leukocyte adherence is mediated by both CD18 and superoxide and that endothelium is necessary for the superoxide-mediated adhesion. In a correlate study, hSOD and MoAb IB4 were shown to attenuate the PAF induced increase in microvascular permeability by 40 and 70%, respectively. These data indicate that the increased microvascular permeability induced by PAF can be attenuated when leukocyte adherence to microvascular endothelium is reduced using molecules that either bind to CD18 adhesive glycoproteins or scavenge superoxide. PMID- 2240226 TI - Transport of biotin in basolateral membrane vesicles of rat liver. AB - We examined biotin transport across the basolateral membrane (BLM) of rat liver using BLM vesicles (BLMV) technique. The purity and suitability for transport studies of liver BLMV were demonstrated by morphological (electron microscopy), enzymatic, and functional criteria. Orientation of liver BLMV was determined by freeze-fracture electron microscopy and by [3H]ouabain binding methodology and was found to be 65.3-69.7% in the right-side-out orientation. Uptake of biotin by liver BLMV was found by osmolarity and temperature studies to be mostly the result of transport of the substrate into an active intravesicular space with little binding to membrane surfaces. Transport of biotin was found to be Na+ gradient dependent with a distinct "over-shoot" phenomenon. Initial rate of transport of biotin as a function of concentration was found to include a saturable component in the presence of a Na+ gradient (out greater than in) but was linear and lower in the presence of a K+ gradient (no Na+). Kinetic parameters of the saturable Na+ gradient-dependent transport process were 0.39 microM and 1,807 fmol.mg protein-1.20 s-1 for the apparent Km and Vmax, respectively. In the presence, but not the absence, of a Na+ gradient (out greater than in), the addition of structural analogues to the incubation medium caused significant inhibition in the transport of 0.079 microM [3H]biotin. Induction, with the use of valinomycin and an inwardly directed K+ gradient, of a relatively positive intravesicular space caused significant inhibition in the initial rate of biotin transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240227 TI - Characterization of cholecystokinin receptors on the sphincter of Oddi. AB - To characterize directly the ability of cholecystokinin (CCK) to interact with receptors on the sphincter of Oddi (SO), we measured binding of 125I-labeled Bolton-Hunter-labeled COOH-terminal octapeptide of cholecystokinin (125I-BH-CCK 8) to tissue sections from the guinea pig SO. Autoradiography localized binding of 125I-BH-CCK-8 over the SO smooth muscle layer. Binding was saturable, specific, dependent on time, pH, and temperature, and was reversible. Binding of 125I-BH-CCK-8 was inhibited by various CCK receptor agonists with the following potencies: CCK-8 much greater than des(SO3)CCK-8 much greater than gastrin-17-I and by various CCK receptor antagonists with the following potencies: L-364,718 greater than proglumide analogue 10 much greater than carbobenzoxy-Tyr(SO3H)-Met Gly-Trp-Met-Asp-NH2 greater than N2,O2' dibutyryl guanosine 3',5'-cyclic monophosphate. The potencies of agonists in stimulating and of antagonists in inhibiting CCK-8-stimulated SO contractions correlated closely with their abilities to inhibit binding of 125I-BH-CCK-8. Analysis of binding of 125I-BH-CCK 8 to SO tissue sections revealed two classes of CCK binding sites: a high affinity site [dissociation constant (Kd) 0.2 nM] and a low-affinity site (Kd 70 nM). Atropine or tetrodotoxin (TTX) caused a similar rightward shift of the CCK-8 dose-response curve for stimulation of SO contraction. Comparison of receptor occupation to CCK-8-induced contraction suggested that CCK-8 occupation of the high-affinity binding site correlated with contraction in the absence of atropine and the low-affinity CCK binding with contraction in the presence of atropine or TTX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240228 TI - Chicken gastrin: a member of the gastrin/CCK family with novel structure-activity relationships. AB - The biological activity of natural chicken gastrins isolated from the "antrum" like region of the chicken gut have been studied on gastric secretion in chickens, turkeys, and rats, pancreatic secretion in turkeys and rats, and gallbladder contraction in chickens and guinea pigs. Natural chicken gastrin was shown to be approximately 85% sulfated on the tyrosine that occurs at position 7 from the COOH-terminus. In both avian and mammalian systems, chicken gastrins were found to be potent stimulants of acid secretion but were virtually inactive as stimulants of pancreatic secretion and gallbladder contraction. Peptides with the COOH-terminal tetrapeptide amide of CCK and a sulfated tyrosine at position 7 from the COOH-terminus are usually potent stimulants of pancreas and gallbladder. However, although chicken gastrin has a CCK-like structure, it has a gastrin-like spectrum of biological actions. A proline immediately adjacent to the sulfated tyrosine may produce a steric effect that lowers the activity of chicken gastrin on pancreas and gallbladder. Evidently, then, the factors that determine specificity of action of CCK and gastrin are different in birds and mammals. PMID- 2240229 TI - Single-nephron responses to systemic administration of amino acids in dogs. AB - It has been suggested that the tubuloglomerular feedback (TGF) system is responsible for renal vasodilation during systemic infusion of amino acid solutions. We evaluated the effect of intravenous administration of amino acids (serine, alanine, proline, and glycine; total dose of 0.075 mmol of amino acids.kg body wt-1.min-1) on whole kidney and single-nephron hemodynamics in pentobarbital sodium-anesthetized dogs. At spontaneous renal arterial pressure (RAP; 125.4 +/- 4.7 mmHg), measurements of single-nephron function obtained during tubular blockade, stop-flow pressure (SFP; 48.2 +/- 2.0 vs. 58.9 +/- 2.3 mmHg, P less than 0.01), and proximally determined single-nephron glomerular filtration rate (SNGFR-TPC; 73.9 +/- 7.0 vs. 93.4 +/- 7.6 nl/min, P less than 0.01) increased in parallel to the increases of outer cortical blood flow (OCBF; 15.4 +/- 1.1 vs. 19.1 +/- 1.5 units, P less than 0.05), renal blood flow (RBF; 4.60 +/- 0.18 vs. 5.73 +/- 0.22 ml.min-1.g kidney wt-1, P less than 0.01), and glomerular filtration rate (GFR; 0.885 +/- 0.034 vs. 1.116 +/- 0.034 ml.min-1.g kidney wt-1, P less than 0.01). Free-flow tubular fluid-to-plasma inulin ratios, determined from late proximal recollections during saline (control) and amino acid infusions failed to provide evidence for altered proximal reabsorption rate (1.63 +/- 0.12 vs. 1.58 +/- 0.17 during amino acids, NS). At reduced RAP (92.6 +/ 1.9 mmHg), where it is presumed that TGF-mediated vasodilation is already near maximal, the vasodilatory response to amino acid infusion was intact and single nephron parameters measured during tubular blockade increased to the same extent as OCBF, RBF, and GFR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240230 TI - Effects of growth hormone and IGF-I on renal function in rats with normal and reduced renal mass. AB - To characterize actions of growth hormone (GH) and insulin-like growth factor ( (IGF-I) on renal function in rats with normal and reduced renal mass, we administered recombinant bovine growth hormone (bGH) or human IGF-I (hIGF-I) to normal rats or to rats that had undergone unilateral nephrectomy and two-thirds infarction of the contralateral kidney, and measured inulin and p-aminohippurate clearances over 10-17 days. Administration of either bGH (100-200 micrograms/day) or hIGF-I (200 micrograms/day) to rats with normal renal mass increased inulin and p-aminohippurate clearances compared with those measured in animals that received vehicle. Filtration fractions were not affected by either bGH or hIGF-I. Inulin clearance was decreased to approximately 17% of normal 1 day after reduction of renal mass in rats. Over the next 3 days insulin clearance increased significantly in rats with reduced renal mass that were administered vehicle. No further enhancement occurred during the next 7 days. Neither bGH nor hIGF-I affected inulin clearance in rats with reduced renal mass. We conclude that both GH and IGF-I enhance glomerular filtration rate when administered to rats with normal renal mass, but not when administered in the same quantities to rats in which renal functional mass is reduced. Glomerular filtration rate increases within 4 days of renal mass reduction independent of exogenous GH or IGF-I. PMID- 2240231 TI - Polarity of kallikrein release and activation in perfused rat kidneys. AB - The polarity of release and activation of renal kallikrein and its regulation by adrenal hormones was studied in isolated perfused rat kidneys. Bilateral adrenalectomy (AX) produced a decrease in kallikrein and prokallikrein excretion into urine and perfusate of isolated kidneys, as well as in active kallikrein excretion in vivo. One-week treatment with deoxycorticosterone acetate (DOCA 2.5 mg/day) or dexamethasone (DEX 0.25 mg/day) increased the urinary output of active and total kallikrein above AX levels but below control. In contrast, neither corticoid increased enzyme secretion to perfusate. Regardless of AX or corticosteroid treatment, the prokallikrein fraction was 90% of total enzyme in perfusate and only 40% in urine. These results confirm that adrenal steroids are necessary for renal kallikrein synthesis and excretion; however, neither DOCA nor DEX appears to be a unique regulator for release or activation of this enzyme. In addition, whereas the processes of secretion and activation toward the urine are regulated in parallel, kallikrein release to the venous effluent seems to be regulated separately. PMID- 2240232 TI - Ion concentrations in the rat CCD: differences between cell types and effect of alkalosis. AB - We have previously shown that the isolated perfused cortical collecting duct (CCD) from chloride-depleted alkalotic (CDA) rats continues to secrete HCO3 for up to 3 h. To determine whether the sustained alteration in transport was associated with changes in intracellular ion concentrations, we performed energy dispersive X-ray microanalysis in microdissected tubule bundles obtained from CDA rats and rats with normal acid-base status (CON). Before analysis, the bundles from both groups were incubated for 1 h in vitro in a modified Ringer solution (pH 7.4, 105 mM Cl). Principal (PC) and intercalated cells (IC) of the CCD from CON animals differed in the nuclear concentration of Na (17.0 vs. 24.7 mmol/l cell water), K (192.5 vs. 177.0 mmol/l cell water), and Cl (17.8 vs. 47.8 mmol/l cell water). Cells of the cortical thick ascending limb of Henle (CTAL) had the lowest Na and Cl values (11.5 and 14.8 mmol/l cell water, respectively). CDA resulted in no systematic Cl changes. In the IC the nuclear Na concentration was significantly increased (32.0 vs. 24.7 mmol/l cell water) and in all cells a small reduction in K concentration was detectable. These findings suggest that 1) the different transport functions of IC, PC, and CTAL are associated with differences in the intracellular ion composition, and 2) the sustained HCO3 secretion seen in CCD from CDA rats cannot be explained as the result of intracellular Cl depletion. PMID- 2240233 TI - Maturation of HCO3- transport in rabbit collecting duct. AB - Newborn rabbits maintain a state of hypochloremic metabolic alkalosis with plasma HCO3- concentrations generally exceeding 27 mM. The large amounts of potential net base in mother's milk probably contribute to the generation of this alkalosis. We surmised that immature handling of H+ or HCO3- by the neonatal collecting duct helps maintain this alkalosis. Net HCO3- transport was measured in perfused collecting ducts taken from maturing rabbits, in solutions simulating adult rabbit plasma ultrafiltrate and then in presence of Cl(-)-free bathing solution. Cortical collecting ducts (CCD) from newborn and 4-wk-old rabbits failed to secrete HCO3- under baseline conditions and could not be stimulated to secrete HCO3- in Cl(-)-free bath. Neonatal segments perfused at very slow flow rates showed significant HCO3- absorption; inhibition of HCO3- secretion by removal of luminal Cl- revealed a substantial HCO3- absorptive flux. Segments from 6-wk-old and mature animals secreted net HCO3- and generally showed more than a fivefold increase in HCO3- secretion after Cl- removal from the bath. Outer medullary collecting ducts (OMCD) from newborn rabbits absorbed HCO3- at rates approaching that of mature segments. We conclude that relatively high rates of HCO3- absorption in OMCD and lack of HCO3- secretion in CCD may contribute to the metabolic alkalosis of the neonatal rabbit. PMID- 2240234 TI - Factors affecting the ratio of different organic osmolytes in renal medullary cells. AB - Renal medullary cells contain high concentrations of sorbitol, inositol, glycerophosphorylcholine (GPC), and betaine, which balance the variably high osmolality of extracellular NaCl. We found that PAP-HT25 (rabbit renal medullary) cells in tissue culture increase their content of all four when medium osmolality is increased by adding NaCl and urea. However, this requires that betaine be added to medium in addition to customary constituents. Some factors affecting the mix of organic osmolytes in these cells during hypertonicity are as follows. 1) Urea in medium increases cell GPC and tends to decrease others, particularly betaine. 2) With small increases in medium NaCl, intracellular inositol is highest, whereas sorbitol predominates with large NaCl increases. 3) When osmolality is suddenly decreased, these four organic osmolytes exit rapidly from cells, but in differing relative amounts (betaine much greater than sorbitol greater than inositol much greater than GPC). 4) Altering cell betaine levels (by varying betaine in medium) causes reciprocal changes in cell sorbitol (by affecting aldose reductase activity) and vice versa, whereas inositol and GPC are less affected. 5) Raising medium glucose concentration (from which sorbitol is synthesized) increases cell sorbitol and decreases cell inositol and betaine. 6) Decreasing the amount of GPC in cells (by removing choline from medium) causes small changes in betaine and sorbitol, but not in inositol. Changing the amount of inositol does not affect the others. Similar interrelations may operate in vivo to vary the mix of organic osmolytes in renal medulla. PMID- 2240236 TI - Role of endothelium in reactive dilation of skeletal muscle arterioles. AB - In cremaster muscle of pentobarbital-anesthetized rats, the role of endothelium in the reactive dilation of an arteriole (mean control diameter: 18.2 +/- 0.5 microns) during and after short (approximately 20 s) or long (approximately 80 s) occlusion of a parent arteriole was investigated. Distal to the occluder, arteriolar diameter increased during the occlusion (mean peak increase: 6.9 +/- 0.4 and 6.7 +/- 1.1 microns, respectively) and increased even further after the release of the occlusion as blood flow was reestablished (additional mean increase: 6.5 +/- 0.7 and 5.8 +/- 0.8 microns, respectively). The duration of arteriolar dilation after the release of the occlusion was dependent on the duration of occlusion (252.2 +/- 37 vs. 411.3 +/- 57 s; P less than 0.05). After impairment of the arteriolar endothelium by light/dye treatment, a dilation was still present during both the shorter and longer occlusions (mean increase: 4.73 +/- 1.4 and 4.73 +/- 1.3 microns, respectively); however, in both cases the additional dilation after release of the occlusion was greatly diminished. The duration of reactive arteriolar responses following impairment of the endothelium was significantly reduced only on release of the shorter occlusions. The results suggest that reactive dilation (hyperemia) of arterioles is the result of multiple, endothelium-dependent and endothelium-independent vasoactive factors. PMID- 2240235 TI - Bladder contributes to eicosanoids excreted in urine. AB - The excretion of eicosanoids was examined in urine collected from the bladder or the ureter in normal rats. We found that the excretion of thromboxane B2 (the stable metabolite of thromboxane A2), prostaglandin E2, and 6-ketoprostaglandin F1 alpha was significantly greater in urine collected from the bladder than in urine collected from the ureter. This suggests that the bladder contributes significantly to the amount of eicosanoids present in the urine. PMID- 2240237 TI - Effects of hypoproteinemia on blood volume and arterial pressure of volume-loaded dogs. AB - Studies were performed in 14 conscious, anephric dogs to clarify the role of blood volume in the genesis of hypertension. The dogs were splenectomized and had plasma protein concentration (PPC) reduced to 2.7 g/dl by daily plasmapheresis for 9 days. This hypoproteinemia resulted in a 20% decrease in both blood volume and mean arterial pressure. On the 10th day the dogs were nephrectomized. On the 11th day after a 3-h control period with plasmapheresis, lactated Ringer equivalent to 10 or 20% of body weight was intravenously infused. By 25 h postinfusion blood volume had not increased, and the dogs were still hypotensive. At 25 h plasma protein mass was returned to normal by intravenous infusion of autologous plasma, the average blood volume of the three low PPC groups increased approximately 50%, and the arterial pressure increased greater than 60%. The decrease in PPC shifted the regression of blood volume on sodium space down the blood volume axis. In conclusion, the dependence of arterial pressure on blood volume was demonstrated by the decrease in both blood volume and arterial pressure after PPC reduction, the constancy of blood volume and pressure during Ringer infusion, and the increase in both volume and pressure after plasma infusion. PMID- 2240238 TI - Effects of sympathectomy on blood pressure and its variability in conscious rats. AB - To further assess the role of the sympathetic nervous system (SNS) in the control of blood pressure (BP), continuous recordings of BP were performed in conscious freely moving rats that had received daily injections of guanethidine or saline from 7 to 90 days of age. Guanethidine extensively destroyed the peripheral sympathetic fibers as indicated by marked decreases in the norepinephrine content of the heart and kidneys and the absence of pressor response to tyramine injection. Such a chronic sympathectomy did not alter the BP and heart rate (HR) levels but markedly enhanced the BP variability while the HR variability and the sensitivity of the cardiac baroreceptor reflex were not altered. Angiotensin converting enzyme inhibition with perindopril induced a rapid fall in BP and normalized the BP variability in sympathectomized animals. It is concluded that in rats, the SNS is not necessary for the full development of the BP level but is essential to buffer the spontaneous variability of BP. After sympathectomy, BP is maintained at nearly normal levels mainly through activation of the renin angiotensin system. PMID- 2240239 TI - Reflex responses of renal nerve activity during isometric muscle contraction in cats. AB - Renal sympathetic nerve activity (RSNA), arterial blood pressure (AP), and heart rate (HR) were measured during isometric muscle contraction of a hindlimb in chloralose-anesthetized cats. In 14 cats RSNA, AP, and HR increased during a 1 min contraction by 45%, 39 mmHg, and 11 beats/min, respectively; however, in three cats there was a brief initial decrease in RSNA followed by an increase. In 11 cats isometric contraction was maintained for 5 min by alternate stimulation of the L7 and S1 ventral roots. In the first 1 min of sustained contraction, there was a positive correlation (gamma = 0.58, P less than 0.005) between RSNA and tension development. Thereafter RSNA remained elevated despite a tension decrease, and there was no significant correlation between these changes. The RSNA response to contraction of both hindlimbs was greater than that to contraction of either hindlimb alone. Passive stretch of the hindlimb muscle significantly increased RSNA. Thus the initial increase in RSNA during sustained contraction is likely due to activation of muscle mechanoreceptors, whereas the later increase is probably caused by activation of the muscle metaboreceptors. PMID- 2240240 TI - Endothelium-dependent L-Arg- and L-NMMA-sensitive mechanisms regulate tone of brain microvessels. AB - Pial arterioles on the surface of the mouse brain were observed via television microscopy and measured with an image-splitting technique. The vessels were dilated by L-arginine (L-Arg) in concentrations as low as 10(-5) M and were constricted in dose-dependent manner by NG-monomethyl-L-arginine (L-NMMA). Both the dilation and the constriction were abolished by endothelial damage. This damage was produced over a short segment of endothelium by a well-established technique that involves exposing the endothelium to a helium-neon laser in the presence of intravascular Evans blue dye. In arterioles that were responsive to 10(-5) M L-Arg, five other L-amino acids, also at 10(-5) M, failed to have any effect. The data provide direct evidence for the endothelium-dependent nature of the responses to L-Arg and L-NMMA in vivo in a defined segment of the cerebral vasculature. L-NMMA inhibited dilation by either L-Arg or acetylcholine. The data are consistent with data from in vitro studies and from studies demonstrating that L-NMMA acutely raises blood pressure. From all these earlier studies it has been hypothesized that there is a continuously acting, endothelium-dependent, L Arg-dependent, and L-NMMA-inhibitable mechanism tending to relax blood vessels. The mediator of this mechanism is thought to be the endothelium-dependent relaxing factor for acetylcholine. Our data suggest that this mechanism is acting in the resistance vessels of the brain in vivo. PMID- 2240241 TI - Finite strains in anterior and posterior wall of canine left ventricle. AB - Piezoelectric crystals were implanted in the anterior and posterior midwall of the left ventricle in six anesthetized dogs to compare regional two-dimensional finite deformations. Increasing left ventricular end-diastolic pressure (LVEDP) from 3 to 18 mmHg caused a similar expansion in the end-diastolic configuration (similar end-diastolic principal strains), but maximal lengthening was more circumferential in the anterior wall (-18 +/- 13 degrees) and more longitudinal in the posterior wall (-54 +/- 19 degrees). End-diastolic in-plane shears were negative in both regions, consistent with a left-handed diastolic torsion. As LVEDP increased, maximal shortening strains increased similarly (similar end systolic principal strains), but there was a preferential increase in end systolic circumferential strain in the anterior wall and preferential increase in longitudinal strain in the posterior wall. End-systolic in-plane shears were small and positive in both regions. The circumferential strain accurately reflected maximal end-diastolic and end-systolic principal strains in the anterior wall at mid and high LVEDP but underestimated the maximal end-diastolic principal strain by 50% and the maximal end-systolic principal strain by 30% in the posterior wall at all LVEDPs. We conclude that the magnitude of end-diastolic and end-systolic strains is similar for anterior and posterior walls over a wide range of LVEDP. However, there are regional differences in the directions of maximal deformation that should be considered when evaluating regional ventricular function. PMID- 2240242 TI - Comparison between force-velocity and end-systolic pressure-volume characterization of intrinsic LV function. AB - We reanalyzed experiments in in situ hearts of 16 open-chest anesthetized dogs, in which two different loading interventions were performed, i.e., an occlusion of the descending aorta (InP) and a rapid volume infusion (InV). Previous studies had demonstrated that the end-systolic elastance (Ees) of the InP was substantially larger than the Ees of the InV suggesting either a load dependency of Ees as such, or an increase in contractility during InP. The data were reanalyzed in the light of the muscular pump concept by plotting peak normalized velocity of circumferential shortening versus a global representative force approximating the left ventricle by a sphere. In all but one experiment the points of the two interventions are located on a single relationship over a very broad range of forces (from 397 to 2,461 g between the control states of experiments and from 602 to 3,278 g difference between control and highest load within experiments). The virtual independence of the force-velocity relation (FVR) and the dependence of the end-systolic pressure-volume relation (ESPVR) on the type of loading intervention can be ascribed to the fact that the former is assessed early during ejection and is therefore less influenced by shortening deactivation and internal resistance than the ESPVR. We conclude that the FVR offers a more consistent characterization of intrinsic LV function than the ESPVR. PMID- 2240243 TI - Antibiotics versus cardiovascular support in a canine model of human septic shock. AB - This study compares the efficacy of antibiotics (cefoxitin and gentamicin), cardiovascular support (fluids and dopamine titrated by intravascular monitoring to hemodynamic end points), and a combination of these two therapies in dogs with septic shock induced by an intraperitoneal clot containing Escherichia coli. Survival rates were 0, 13, 13, and 43% in groups receiving no therapy (controls), antibiotics alone, cardiovascular support alone, or combined therapy (P less than 0.01), respectively. The improved survival observed in the group receiving combined therapy considerably exceeded that in the groups receiving either therapy alone (i.e., a synergistic increase P less than 0.05). Compared with antibiotics alone, cardiovascular support alone prolonged survival time (P less than 0.006). All groups developed similar and significant (P less than 0.01) increases in endotoxin levels; however, in the combined therapy group, nonsurvivors (compared with survivors) had higher levels of endotoxemia (P less than 0.05). Although survivors and nonsurvivors in the combined therapy group required similar (P = 0.10) quantities of fluid therapy, nonsurvivors gained more weight (P less than 0.05), suggesting abnormal vascular permeability with extravascular retention of fluids in the nonsurvivors. This study demonstrates that antibiotics alone and cardiovascular support alone are relatively ineffective in the treatment of septic shock. When combined, however, these two therapies provide moderately successful treatment for this highly lethal disorder. PMID- 2240244 TI - Permeability of time-dependent K+ channel in guinea pig ventricular myocytes to Cs+, Na+, NH4+, and Rb+. AB - Currents through time-dependent K+ channels (also referred to as IK or the delayed rectifier) were studied with the whole cell patch-clamp technique in isolated guinea pig ventricular myocytes. IK measurements were restricted to the examination of deactivation tail currents. Substitution of various monovalent cations for external K+ produced shifts of the reversal potential of IK. These shifts were used to calculate permeability ratios relative to K+. The permeability sequence for the IK channels was K+ = Rb+ greater than NH4+ = Cs+ greater than Na+. Time-dependent outward currents were also examined when the myocytes were dialyzed with Cs+ instead of K+. A sizeable time-dependent outward current, quite similar to that seen with K+ dialysis, was demonstrated. This current was primarily carried by intracellular Cs+, as the reversal potential of the current shifted 46 mV per 10-fold change of external Cs+ concentration. The significance of Cs+ permeation through IK channels is discussed with respect to the common use of Cs+ in isolating other currents. PMID- 2240245 TI - Effect of atrioventricular relationship on ventricular refractoriness in humans. AB - Right ventricular refractory periods obtained using atrial and ventricular pacing with an atrioventricular (AV) interval of 160 ms were compared with those obtained with an AV interval of 0 ms in a group of 53 patients. The mean right ventricular effective refractory periods were longer at an AV interval of 160 ms than at an AV interval of 0 ms at pacing cycle lengths of 600 (mean 2.5 +/- 1.8 ms difference) and 400 ms (mean 3.8 +/- 2.4 ms difference; P less than 0.01). In a subset of 10 patients, left ventricular volumes measured by two-dimensional echocardiography demonstrated that pacing with an AV interval of 160 ms was associated with a higher end-diastolic volume and stroke volume than pacing with an AV interval of 0 ms (P less than 0.001). Autonomic blockade did not alter the relationship between AV interval and ventricular refractoriness. We conclude that 1) right ventricular refractory periods are shorter at an AV interval of 0 ms than at an AV interval of 160 ms; 2) these differences are not caused by changes in autonomic tone but are associated with differences in ventricular volumes; and 3) if precise determinations of ventricular refractoriness are desired, then the timing of atrial systole should be controlled by atrial pacing. PMID- 2240246 TI - Interstitial adenosine in guinea pig hearts: an index obtained by epicardial disks. AB - Epicardial porous disks were used to estimate left ventricular interstitial fluid adenosine in the isolated guinea pig heart perfused at constant flow. To validate this technique, adenosine was infused with 0.5 microM dipyridamole and 5 microM erythro-4-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA) to inhibit adenosine uptake and deamination, respectively. Under these conditions, with 6 or 12 microM adenosine in the arterial infusate, the venous and steady-state left ventricular disk adenosine values equaled those of the perfusion fluid, reflecting the expected equilibration between vascular and left ventricular interstitial fluid (disk) compartments. The concentration of endogenous adenosine in the interstitial fluid as estimated by the epicardial disks under control conditions was 0.28 +/- 0.03 microM with a concomitant coronary sinus concentration of 0.004 +/- 0.001 microM. We conclude that a marked adenosine gradient exists between the interstitial fluid and the vascular space and that disk adenosine measurements provide a useful index of left ventricular interstitial fluid adenosine. PMID- 2240247 TI - Recombinant human interleukin 1 alpha dilates pial arterioles and increases cerebrospinal fluid prostanoids in piglets. AB - Effects of recombinant human interleukin 1 alpha (IL-1 alpha) on vasomotor tone of pial arterioles and cerebrospinal fluid (CSF) prostanoid levels were examined in anesthetized piglets by employing the closed cranial window method. IL-1 alpha in a dose of 10.8 micrograms infused under the window increased pial arteriolar diameter [initial size, 160 +/- 9 (SE) micrograms] significantly at 15 min postinfusion through 30 min (30-min study), exhibiting a maximum dilation of 13 +/- 1% (n = 8) over the control levels. Significant increases in levels of prostaglandin E2 (PGE2, 75%), 6-keto-PGF1 alpha (84%), and PGF2 alpha (35%) but not for thromboxane B2 (TxB2, 2%) were observed when CSF was sampled from under the window 30 min after 10.8 micrograms IL-1 alpha. A lower dose of IL-1 alpha (1.0 micrograms, n = 4) significantly increased the diameter of pial arterioles with a tendency for longer onset (25-30 min) and smaller magnitude (9-10%) than the higher dose. In IL-1 alpha time-response studies, CSF sampled 10 min after 10.8 micrograms IL-1 alpha infusion (10-min study, n = 6) under the window exhibited the same levels of PGE2, 6-keto-PGF1 alpha, PGF2 alpha, and TxB2 as those of the controls. There was no vasodilation in the 10-min study. However, when sampled 20 min after 10.8 micrograms IL-1 alpha (20-min study, n = 6), CSF levels of all prostanoids except for TxB2 significantly increased over the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240248 TI - Three-dimensional mapping of acute ischemic regions using MRI: wall thickening versus motion analysis. AB - Three-dimensional (3D) endocardial wall motion and thickening were compared as quantitative methods for distinguishing ischemic from non-ischemic myocardium and for their potential to map regional left ventricular (LV) function. Data were obtained by gated magnetic resonance (MR) images in seven open-chest dogs with acute ischemia. The LVs were reconstructed in 3D at end diastole (ED) and end systole (ES) with a helical coordinate system that wraps the endocardium and epicardium. Thickness and percent wall thickening were calculated by a 3D volume element method. Wall motion was calculated by the 3D displacement of the endocardium perpendicular to the wall using both fixed and floating centroids. Monastral blue nonstaining identified the ischemic regions from five anatomical slices of the LV, which corresponded to the in vivo image planes. Thickening and motion were compared at the centers of the ischemic and the remote normal zones, in addition to comparing the functional maps of the entire LV to the postmortem anatomical maps. All methods distinguished between the center of the ischemic zone and the remote normal zone; however, thickening discriminated most strongly between zones. Comparison of the 3D in vivo maps with the 3D postmortem maps showed that the sensitivity, specificity, and overall accuracy of the thickening algorithm exceeded those obtained by the wall motion algorithms with fixed or floating centroids. Thus wall thickening utilizing the 3D volume element approach is superior to 3D wall motion algorithms in distinguishing ischemic from nonischemic zones and in mapping regional function in the entire LV. PMID- 2240249 TI - Influence of dietary n-3 fatty acids on myocardial ischemia and reperfusion. AB - We have investigated the effect of elevated n-3 (omega-3) fatty acid content in the diet on arrhythmias, ischemic damage, and inflammatory cell infiltration into the reperfused left ventricular free wall (LVFW). Weanling rats were fed purified diets in which the lipid was replaced with either corn oil (CO) or menhaden oil (MO). After 4 wk, MO feeding resulted in significant elevations in both the ratio of n-3 to n-6 fatty acids and the unsaturation index in myocardial phospholipids. Rats were subjected to 15 min of ischemia followed by reperfusion. After 6 h of reperfusion of the left coronary artery there was significantly less creatine kinase (CK) lost from the LVFW of rats fed MO. Leukocyte infiltration into the LVFW, as measured by myeloperoxidase (MPO) activity, was also significantly reduced with MO feeding at 6 h. Arrhythmias were studied in a separate group of 17 rats; both the incidence and severity of ventricular tachycardia and ventricular fibrillation were significantly reduced during the ischemic and reperfusion periods with MO feeding. After 24 h of reperfusion there was also significantly less CK lost from the LVFW of MO-fed rats; however, there was no significant difference in tissue MPO activity in ventricular homogenates. Survival after 24 h of reperfusion was 76% (16/21) for MO- and 41% (9/22) for CO fed rats. The data suggest a protective effect for dietary MO in myocardial ischemia-reperfusion, which may involve both an early reduction in leukocyte infiltration and a reduction in the incidence of fatal arrhythmias. PMID- 2240250 TI - Myocyte structure, function, and calcium kinetics in the cardiomyopathic hamster heart. AB - The hereditary cardiomyopathic strain of the Syrian hamster has been studied extensively as a model of cardiomyopathy and heart failure. However, the primary defect underlying the cascade of events leading to heart failure has not been identified. In the present study, isolated cardiac cells were obtained for study from 8-mo-old cardiomyopathic (Bio 14.6) and age-matched normal hamsters (F1B). We examined the relationships among structure, contractile function, and calcium kinetics in these isolated cardiomyocytes. The cardiomyopathic myocytes were wider and longer than controls, and myopathic cells were less calcium tolerant. The sarcoplasmic reticulum and T-tubule systems from myopathic hearts were more abundant as determined by electron microscopy. The amplitude and velocity of contraction was decreased in cardiomyopathic cells, whereas diastolic relaxation velocity was not different between the two groups. The size of the rapidly exchangeable calcium pool determined by 45Ca2+ uptake was significantly increased in cardiomyopathic myocytes. Time-averaged cytosolic Ca2+ in these cells (472 +/- 60 nM) was significantly higher than control (260 +/- 15 nM) as measured by the fura-2 fluorescence ratio. When extracellular Ca2+ ([Ca2+]o) was increased to greater than 1.2 mM, the resulting increase in intracellular calcium concentration was less than that in normal control cells. The corresponding [Ca2+]o-induced increase in amplitude of cell motion was significantly attenuated in the cardiomyopathic cells compared with normal control myocytes. We conclude that distinct abnormalities of contractile function and calcium homeostasis can be identified in single cells isolated from cardiomyopathic hamster hearts. PMID- 2240251 TI - Nature of defibrillation: determinism versus probabilism. AB - The gradual transitions that are found between unsuccessful and successful shock strengths in percent success or dose-response curves suggest that defibrillation is a probabilistic phenomenon. This concept appears to be reinforced by the fact that a frequency distribution is observed in defibrillation threshold data and that a dose-response relationship is also obtained by integration of the frequency distribution. The purpose of this study was to investigate whether a deterministic threshold model (based on experimental results) could produce 1) gradual transitions in dose-response curves, and 2) a threshold frequency distribution for individual subjects. In the experimental phase of the study, a linear deterministic relationship was found between transthoracic threshold current and defibrillation episode number (other variables held constant) in pentobarbital-anesthetized dogs. The correlation coefficient for each dog was between 0.77 and 0.98 (P less than 0.01), and both positive and negative slopes were found. Based on these results, threshold current was modeled for computer simulation as a linear function of episode number. The model was thus purely deterministic with no random variability. For each simulated experiment, several parameters were varied: order of shocks (increment, decrement, random order), slope of threshold function, and percent error of the initial threshold. Several hundred computer simulations were performed to determine the effect of varying these parameters. In all cases, threshold-frequency distributions and sigmoidal dose-response curves with gradual transitions were produced. The results of this investigation demonstrate that the apparent probabilistic behavior of defibrillation can be produced by a deterministic relationship. PMID- 2240252 TI - Age-related cerebrovascular response to global ischemia in pigs. AB - We tested the hypothesis that 1- to 2-wk-old pigs (piglet) have improved recovery of cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and somatosensory-evoked potentials (SEP) compared with 6- to 8-mo-old pigs (pig) after transient global cerebral ischemia. All animals were anesthetized with pentobarbital sodium. After tracheostomy ventilation was adjusted to maintain normoxia (arterial oxygen pressure, 100-150 mmHg) and normocarbia (arterial carbon dioxide pressure, 35-40 mmHg). Arterial blood gases, blood pressure, and hemoglobin concentration remained within physiological limits throughout the experiment. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta. During ischemia the electroencephalogram and SEP became isoelectric within 40 and 120 s, respectively. At 10 min of reperfusion hyperemia occurred in most brain regions (e.g., whole brain: piglet, 270 +/- 45%; pig, 316 +/- 48%). In pigs delayed hypoperfusion occurred in all regions except white matter. In contrast, piglets only had delayed hyperperfusion to the brain stem and caudate nucleus. Throughout reperfusion CMRO2 was decreased in pigs (3.3 +/- 0.4 to 1.9 +/- 0.2 ml.min-1.100 g-1) but was not different from control (2.7 +/- 0.3 ml.min-1.100 g-1) in piglets. By the end of reperfusion SEP amplitude was closer to control in piglets than pigs (55 +/- 9 vs. 32 +/- 4% of control). We conclude that 1- to 2-wk-old piglets have quicker return of CBF, CMRO2, and SEP to control values after global ischemia, which mechanistically may explain previous reports of improved neurological recovery in young animals after transient ischemia. PMID- 2240253 TI - Myocardial electrophysiological effects of vasoactive intestinal peptide in dogs. AB - Vasoactive intestinal peptide (VIP) is a potent inotrope and coronary vasodilator. To test whether VIP also exerts regional myocardial electrophysiological (EP) effects, dose-response and time-course effects of intracoronary injections (10(-10)-10(-4) M) were obtained in 4 intact hearts and 12 in situ normoperfused right ventricular flap preparations in chloralose anesthetized dogs. Under constant rate, activation (A), recovery (R), and A-R interval (ARI) maps were constructed from multiplexed unipolar surface electrograms recorded simultaneously from 32 sites. Effects were compared with those of isoproterenol (Iso) and forskolin (For). The main finding with all agonists was the uniform shortening of ARIs in a dose-response fashion with a maximum of 30 +/- 4 ms or 20% from control. Although the maximal EP changes were similar for all agonists, they occurred at different molecular concentrations (10(-6) Iso, 10(-5) VIP, and 10(-4) For). Also, whereas the duration of EP effect did not exceed 5 min for Iso and For, it was markedly sustained for VIP, outlasting its contractile but paralleling its vasodilatory effect. The physiological endoepicardial differences in ARI and the recovery sequence were preserved for all agonists. Thus VIP, in addition to coronary vasodilation and myocardial inotropy, exerts a strong balanced global myocardial EP effect, similar to, but more sustained than, the adrenergic effect. The difference in duration of inotropic and EP effects may point to different mediating mechanisms. PMID- 2240254 TI - Metabolic and functional consequences of barium-induced contracture in rabbit myocardium. AB - Barium contracture tonically activates myocardium while preserving cellular integrity. We studied the metabolic and mechanical consequences of sustained Ba2+ contracture. We measured the time course of phosphocreatine (PCr), ATP, Pi, total phosphate, and intracellular pH via 31P nuclear magnetic resonance (NMR) in isolated, isovolumic rabbit hearts. For mechanical studies, we measured force transients and dynamic stiffness in excised rabbit right ventricular papillary muscles at different elapsed times in Ba2+ contracture. In the perfused hearts, PCr fell steadily to 20% of control after 60 min. ATP remained constant for approximately 25 min then fell to 25% by 60 min. Pi rose to 200% within 15 min and then remained unchanged, whereas total phosphate dropped steadily to 50% of control by 60 min. Myocardial O2 consumption remained near control for 30 min and then declined to 50% by 60 min. Consistent with ATP and O2 consumption measurements, mechanical responses were unchanged for approximately the first half hour. Because of the elevated Pi, however, myofilament kinetics may have been accelerated compared with the control metabolic state. After the initial period of stable contracture, the gradual alteration of mechanical behavior exhibited a progressive trend toward more rigor-like characteristics. In summary, myocardium in Ba2+ contracture is metabolically and mechanically stable for approximately 30 min but begins to degrade thereafter. When compared with other tonic states of activation, Ba2+ contracture appears to be less demanding energetically. PMID- 2240256 TI - Analysis of thermopile records from contracting isolated cardiac muscle. AB - Recovery heat production after contraction in rabbit papillary muscle at 20 degrees C occurs at an exponentially declining rate. The time constant describing this decline is 25 s; it is not different when 10 twitches or when a steady-state twitch train is studied, and it is unaltered by changing stimulus frequency from 0.125 to 0.2 Hz. The same value has previously been found after single twitches. If it is assumed that phosphocreatine (PCr) resynthesis is the cause of recovery heat production and that it occurs also during contractions at a rate proportional to the amount of PCr depletion, it is possible to divide the total heat production for any period of stimulation into that caused by this recovery process (R) and that caused by initial (I) processes (presumed to be PCr splitting). The value of R/I obtained by using this method is 1.10 +/- 0.04 (means +/- SE, n = 27 muscles), close to the theoretical value of 1.13. The correspondence between the measured and the predicted ratio supports the assumptions underlying the measurement. Thus in heart muscle the heat produced during and after contraction can be explained by PCr splitting and reformation. The older Bugnard method of analysis applied to the same data gives an R/I value of 1.5; the reasons for the discrepancy are described. PMID- 2240255 TI - Evidence for protein kinase C involvement in arteriolar myogenic reactivity. AB - Little information exists as to the cellular events that couple the myogenic contractile response of an arteriole to an acute rise in intravascular pressure. The aim of this study was to examine whether protein kinase C (PKC), which has been implicated in the contractile response to agonists, contributes to myogenic vasoconstriction of cremaster muscle arterioles. Studies were performed on anesthetized rats, enclosed in an airtight Plexiglas box, with the cremaster exteriorized into a bath containing Kreb's solution. Pressure in the box was increased to elevate intravascular pressure by 20 mmHg. To examine PKC involvement, studies were performed in the absence or presence of inhibitors of PKC: H 7 (10(-9)-10(-5) M) or staurosporine (10(-10)-10(-7) M). Inhibitors were added to the tissue bath and produced no observable systemic effects or alterations in arteriolar diameter. Third-order arteriole (16 +/- 1 microns diam) responses to these agents and alterations in intravascular pressure were monitored by in vivo microscopy and vessel diameter was measured with a video caliper. H 7 produced a concentration-dependent inhibition of myogenic vasoconstriction, inhibiting the extent of constriction by 75% at 10(-5) M. Similarly, staurosporine caused a concentration-dependent inhibition of pressure induced constriction. At 10(-7) M staurosporine the myogenic response was inhibited by 82%. Further support for a role for PKC in the myogenic response was provided by the observation that indolactam (10(-6) M), a stimulator of PKC activity, induced myogenic reactivity in first-order arterioles, which under basal conditions show passive distension to increased intravascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240257 TI - Coronary resistance increase by nondefatted albumin in saline-perfused rabbit hearts. AB - In isolated hearts perfused with salt solutions, albumin is often added in low concentrations for preservation of endothelial function. Albumin in low concentrations is also sometimes used as an intravascular indicator in such preparations. We perfused isolated rabbit hearts according to Langendorff with a constant flow of Tyrode solution. Despite maximal vasodilation with 10 microM adenosine, coronary vascular resistance increased by 14% after 0.3 g/100 ml nondefatted bovine serum albumin (Sigma A-9647) was added to the perfusate compared with the control resistance with no albumin present. The 50% response time for the vasoconstrictive response to the step change in albumin concentration was 20 +/- 13 s (mean +/- SD). When 0.3 g/100 ml of defatted albumin (Sigma A-6003) was added, the resistance increase was only 1.4% and is explained by increased viscosity. Vasoconstrictive effects of certain nondefatted albumin preparations must be taken into account by investigators who perfuse organs with albumin-containing solutions. PMID- 2240259 TI - Circulatory effects of endothelin in newborn piglets. AB - Endothelin, a recently described endothelial cell-derived peptide, produces pulmonary and coronary vasoconstriction in mature animals. We investigated the acute hemodynamic effects of porcine endothelin in 14 anesthetized open-chest new born piglets during normoxia (Pao2 = 102 +/- 5 mmHg) and hypoxia (fractional inspired O2 concentration = 0.12 X 15 min, Pao2 = 31 +/- 1 mmHg). Six of these animals were pretreated with indomethacin, a cyclooxygenase inhibitor. Low-dose (100 pmol/kg) intravenous bolus injection of endothelin decreased pulmonary vascular resistance index (PVRI) (42 +/- 6 to 16 +/- 4 mmHg.l-1.min.kg, P less than 0.01) and increased coronary blood flow (CBF) (17 +/- 2%, P less than 0.01); cardiac index (CI) and coronary vascular resistance were unaffected. The pulmonary and coronary responses to endothelin were preserved during hypoxia: PVRI fell (160 +/- 22 to 83 +/- 13 mmHg.l-1.min.kg, P less than 0.05) and CBF rose (35 +/- 11%, P less than 0.05). Low-dose endothelin moderately increased mean arterial pressure (61 +/- 3 to 75 +/- 6 mmHg, P less than 0.05) and systemic vascular resistance index (SVRI) (375 +/- 23 to 491 +/- 41 mmHg.l-1.min.kg, P less than 0.01). High-dose (1,000 pmol/kg) endothelin mildly decreased PVRI (51 +/- 7 to 35 +/- 12, NS), moderately increased SVRI (375 +/- 45 to 594 +/- 95 mmHg.l-1.min.kg, P less than 0.05), and markedly diminished CBF (-54 +/- 6%, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240258 TI - Quinidine blocks adenosine 5'-triphosphate-sensitive potassium channels in heart. AB - The ATP-sensitive potassium channel current (IK-ATP) was studied in excised inside-out patches from rat ventricular cells at 20-23 degrees C. The bath solution contained 140 mM KF, and the pipette solution contained 140 mM KCl and 1.2 mM MgCl2. ATP (0.5 mM) in the bath inhibited IK-ATP. In the absence of ATP, 10 microM quinidine decreased open probability 67 +/- 1% (n = 6) at -50 mV and 28 +/- 12% at -130 mV (n = 5) without affecting single channel conductance (48-52 pS). The block increased with 25 and 50 microM quinidine and could be reversed on washing quinidine for several minutes. Interburst (closed) intervals were increased by quinidine, whereas open and closed time distributions within bursts were not changed. We conclude that quinidine blocks IK-ATP in a "slow" and voltage-dependent manner in clinically relevant concentrations. Because of the postulated role for IK-ATP in cardiac ischemia, quinidine block of this channel may play a role in ischemic arrhythmias. PMID- 2240260 TI - Effects of reduced uterine blood flow on fetal cardiovascular, renal, and lung function. AB - Uterine blood flow (UBF) was reduced for 1 h by partially occluding the maternal aorta below the renal arteries in seven pregnant ewes (gestation age 126-134 days). Fetuses became hypoxic, acidemic, and hypercapnic. They developed hypertension (P less than 0.005) and a bradycardia (P less than 0.05). During restricted UBF, fetal hematocrit (Hct) rose (P less than 0.005) and blood volume fell in five of seven fetuses. After release of constriction, fetal Hct fell, and blood volume rose by 7.5 +/- 3.26% (P less than 0.05) relative to control. During reduced UBF, lung liquid and urine flow rates fell (P less than 0.025 and P less than 0.05, respectively). After the occluder was released, Na excretion (which did not fall significantly during reduced UBF) increased (P less than 0.05), and fractional reabsorption of Na fell (P less than 0.05). Changes in fetal blood volume (FBV) were directly related to changes in maternal lower body flow (r = 0.47, P = 0.01, n = 33), and changes in fetal Hct were inversely related to maternal flow (r = -0.635, P = 0.001). Fetal urinary Na excretion per kilogram body weight was directly related to FBV per kilogram (r = 0.44, P = 0.005, n = 40), whereas fractional reabsorption of Na was inversely related to FBV per kilogram body wt (r = 0.48, P less than 0.002, n = 39). It is concluded that reductions in UBF cause fetal hypoxemia and acidemia, which lead to changes in fetal cardiovascular function and in FBV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240261 TI - Salt sensitivity in hypertensive rats with angiotensin II administration. AB - We examined the salt sensitivity of blood pressure in angiotensin II (ANG II) induced hypertension. Wistar rats, salt loaded (0.66, 2, or 8% salt-containing diet) for 4 or 12 days, were infused intravenously with 15 or 60 ng/min of ANG II. Systolic blood pressure (SBP) was not increased by long-term (12 days) salt loading, and SBP was unchanged with ANG II and normal-salt (0.66%) diet. However, when combined with salt loading, ANG II produced hypertension in a dose-dependent fashion; compared with control (120 +/- 2 mmHg), SBP was increased with 15 ng/min of ANG II and 8% salt diet (145 +/- 5 mmHg, P less than 0.05) and with 60 ng/min of ANG II and either 2 or 8% salt diet (149 +/- 8 and 174 +/- 8 mmHg, P less than 0.05, respectively). Na space (exchangeable Na) was increased in a roughly similar pattern and correlated significantly (r = 0.531, P less than 0.05) with SBP. However, with 15 ng/min of ANG II, Na space was not different among rats on either level of salt loading, although the 8% salt diet elevated SBP. Data obtained with short-term (4 days) treatment indicate that an elevated Na space preceded development of hypertension. With 15 ng/min of ANG II and 8% salt diet for 4 days, Na space was markedly (P less than 0.05) increased, but SBP was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240262 TI - Role of central mineralocorticoid binding sites in development of hypertension. AB - The possibility that central mineralocorticoid binding sites are involved in the development of mineralocorticoid hypertension was examined using chronic blockade of these sites with a specific mineralocorticoid receptor antagonist RU 28318 administered by intracerebroventricular (icv) infusion. The antagonist significantly attenuated the development of deoxycorticosterone acetate (DOCA) salt hypertension, but the development of one-kidney, one-clip renal hypertension was not affected. This antihypertensive action was attributable to a central action, since intraperitoneal infusion of the same dose of mineralocorticoid antagonist did not alter the peak development of DOCA-salt hypertension. The icv infusion of RU 28318 did not change either the increase of fluid intake induced by DOCA-salt treatment or the pressor reactivity to centrally or peripherally injected arginine vasopressin and angiotensin II and peripherally administered phenylephrine. The antihypertensive action of icv infusion of the mineralocorticoid antagonist was associated with a reduction of neurogenic vasomotor tone and a restoration of impaired arterial baroreflexes. We conclude that functional integrity of central mineralocorticoid binding sites is required for the full development of DOCA-salt hypertension. PMID- 2240263 TI - Light-dark cycle modulates drinking to homeostatic challenges. AB - Both homeostatic and rhythmic variables are empirically and theoretically important controls of behavior. Yet, drinking behavior has been studied largely from one point of view or the other. The present study examined both homeostatic and rhythmic variables and found evidence for an important interaction of these two types of control of drinking behavior. The drinking rhythm of rats on a light dark cycle was established. Water intake after cellular- or extracellular-related challenges was then measured both at a time of a peak and at a time of a trough of the drinking rhythm. The results indicate that rats drink more water after challenges in their early active phase than in their early inactive phase. The results demonstrate that rhythmic variables modulate the homeostatic controls of drinking behavior. The importance of the interaction of homeostatic and rhythmic variables in models of integrative control of behavior is discussed. PMID- 2240264 TI - Stimulatory effects of cold exposure and cold acclimation on glucose uptake in rat peripheral tissues. AB - The effects of cold exposure on the net rates of 2-[3H]deoxy-D-glucose uptake (Ki) in rat peripheral tissues were investigated comparatively in warm- and cold acclimated animals to determine whether cold acclimation induces regulatory alterations in glucose metabolism. Acute exposure of warm-acclimated (25 degrees C) rats to cold (48 h at 5 degrees C) markedly increased the Ki values in red and white skeletal muscles (2-5 times), in the heart (8 times), in several white adipose tissue (WAT) depots (4-20 times), and in brown adipose tissue (BAT) (110 times). After cold acclimation (3 wk at 5 degrees C), the Ki values further increased in the heart (15 times) and WAT (up to 29 times) but decreased in BAT (36 times). Remarkably, glucose uptake was still increased in muscles of cold exposed/cold-acclimated animals (that do not shiver), demonstrating that enhanced glucose uptake may occur in muscles in the absence of shivering thermogenesis (or contractile activity). When cold-acclimated rats were returned to the warm for 18 h, the Ki values of all tissues, except WAT, returned to control levels. Cold exposure synergistically potentiated the stimulation of tissue glucose uptake induced by a maximal effective dose of insulin (0.5 U/kg iv) in warm- as well as in cold-acclimated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240265 TI - Role of renal sympathetic nerves in response of the ovine fetus to volume expansion. AB - To investigate the role of renal sympathetic nerves in the fetal response to hypervolemia, studies were carried out in conscious, chronically instrumented fetal sheep aged 137-142 days of gestation. Bilateral renal denervation (n = 9) or sham surgery (n = 8) was carried out under halothane anesthesia 3-6 days before experiments. Bilateral renal denervation did not alter basal fetal renal hemodynamics, glomerular filtration rate (GFR), or Na+ excretion. Volume expansion with 6% Dextran 70 (18 ml/kg) was associated with a fall in fetal hematocrit, a sustained increase in mean arterial blood pressure, and a sustained diuresis and natriuresis. There was no significant change in GFR during fetal hypervolemia from control levels of 4.51 +/- 0.74 ml/min (intact) and 4.43 +/- 0.43 ml/min (denervated). Atrial natriuretic factor increased from 144 +/- 34 to 464 +/- 134 pg/ml, and plasma renin activity decreased from 5.15 +/- 1.7 to 3.04 +/- 1.0 ng.ml-1.h-1 in intact animals, within 30 min of completion of the dextran infusion. Similar changes occurred in denervated fetuses. Plasma aldosterone levels remained constant in intact and denervated fetuses during hypervolemia at control levels of 40.8 +/- 5.4 and 59.3 +/- 8.4 pg/ml, respectively. These findings suggest that renal sympathetic nerves do not influence basal renal hemodynamics or function and do not appear to play an important role in the natriuretic response to volume expansion during fetal life. This can be explained by a low tonic renal nerve activity before birth. PMID- 2240266 TI - Vasopressin and oxytocin in rat brain in response to prostaglandin fever. AB - Urethan-anesthetized rats were used to identify effective stimuli for the release of the peptides arginine vasopressin (AVP) and oxytocin into the ventral septal area (VSA) of the brain. Febrile responses to intracerebroventricular injection of prostaglandin E1 (PGE1) were observed in rats whose body temperatures were maintained at 35, 37, or 39 degrees C. Microinjection of the AVP antagonist d(CH2)5Tyr(Me)AVP into the VSA enhanced fever only when PGE1 administration was associated with a significant rise in body temperature. Passive elevation ("artificial fever") or reduction of body temperature in the absence of a PGE1 stimulus was not affected by the antagonist. Push-pull perfusion of the VSA and the dorsal hippocampus, followed by radioimmunoassay of perfusates for AVP and oxytocin, revealed enhanced release into the VSA of AVP only when PGE1 administration was followed by a rise in body temperature. Oxytocin was released whenever body temperature was raised. Peptide concentrations in simultaneous perfusates of dorsal hippocampus did not change in response to PGE1 administration or to passive elevation of body temperature. We conclude that AVP is released into the VSA, but not the dorsal hippocampus, of the rat during a fever induced by PGE1. Oxytocin is released into the VSA, but not the hippocampus, when temperature is elevated. PMID- 2240267 TI - Simulation of mechanoenergetics of asynchronously contracting ventricle. AB - We simulated mechanoenergetics of ventricular asynchronous contraction using a model comprising two compartmentalized asynchronous time-varying elastic elements, E1 and E2. Their elastances [e1(t) and e2(t)] waxed and waned cyclically with a variable time lag (tau). The pressure-volume area (PVA1 or PVA2) circumscribed by the maximum (emax) and minimum e1(t) or e2(t) lines and the contracting pressure-volume trajectory of E1 or E2 quantifies the mechanical energy generated by a contraction of E1 or E2. Similarly, the PVA circumscribed by the resultant Emax (ventricular contractility index) line, the end-diastolic pressure-volume (P-V) line, and the systolic P-V trajectory quantifies the mechanical energy of the entire ventricle. PVA of the ventricle is equal to the sum of PVA1 and PVA2. We found that Emax decreased with increases in tau despite constant emax, and hence ventricular PVA decreased with increases in tau. This simulation helps us to better understand the mechanism of decreased oxygen consumption with increasing ventricular asynchrony reported in the literature. PMID- 2240268 TI - Different in vivo metabolic activities of suprachiasmatic nuclei of Turkish and golden hamsters. AB - The 14C-labeled 2-deoxy-D-glucose technique was used to measure in vivo glucose utilization of the suprachiasmatic nuclei (SCN) of Turkish and golden hamsters during the middle hours of the light phase of the 12:12 h light-dark cycle. The nuclei were clearly visible on autoradiographs made from the brains of Turkish hamsters, and their rate of glucose utilization (69 +/- 6 mumol.100 g-1.min-1) was similar to that previously measured in other rodents, whereas the nuclei were hardly visible on autoradiographs from golden hamsters, and their rate (33 +/- 2 mumol.100 g-1.min-1) was less than half this value. Thus the high energy metabolism characteristic of the SCN of most species is not required for the circadian pacemaker in the nuclei to generate its oscillation. PMID- 2240269 TI - Relationships between plasma ketones and fasting duration in neonatal elephant seals. AB - Long-duration fasting in mammals can ultimately lead to stage three terminal starvation, which is characterized by depleted fat stores, a metabolic shift away from fat metabolism toward lean tissue catabolism, and a sharp decline in circulating levels of plasma fatty acids and ketone bodies. However, this biochemical shift has never been observed outside of the laboratory in a naturally fasting, nonhibernating mammal. In the current study, plasma levels of the ketone body D-beta-hydroxybutyrate (beta-HBA) were assayed in 10 Northern elephant seal pups during suckling and the postweaning fast and in 12 fasting adult seals. Plasma beta-HBA concentration in the pups was minimal during suckling (0.09 +/- 0.06 mM; n = 10) and began to increase immediately after weaning. The concentration rose until about 55 days into the fast (1.34 +/- 0.36 mM; n = 10) and then declined sharply. Within 10 days of this deflection point, the seal pups left for sea. By contrast, adult elephant seals showed consistently low levels of beta-HBA after several months of fasting (0.06 +/- 0.07 mM; n = 12). The data suggest that the duration of fasting in elephant seal pups may be determined, in part, by biochemical shifts that occur near the end of the fast and that the regulation of ketone concentration is different in fasting neonatal and adult elephant seals. PMID- 2240270 TI - Repeated measurement of gastric emptying in rats. PMID- 2240271 TI - Long-term arterial pressure control: an analysis from animal experiments and computer and graphic models. AB - Long-term arterial pressure control is very different from acute control, because many of the acute control systems are overridden by a single long-term mechanism that has little to do with short-term control. This is the renal fluid volume mechanism for pressure control. It is based on a simple functional property of the kidney: as the arterial pressure rises, the kidney output of water and electrolytes increases dramatically. When the output rises above the net intake of water and electrolytes, negative body fluid balance occurs, causing both the body fluid volume and the pressure to decrease. This decrease continues until the kidney fluid output exactly balances the net fluid intake. Conversely, if the pressure falls below the exact level for balance, intake becomes greater than output; then fluid builds up in the body and the pressure rises until intake and output again exactly balance each other. This fluid mechanism for pressure control has been known from the beginning of blood pressure research. However, its overpowering importance was not appreciated until a mathematical computer analysis in 1966 demonstrated the renal-fluid feedback mechanism to have infinite feedback gain for long-term pressure control. This is the principal topic of the present review. PMID- 2240272 TI - Neurogenesis of respiratory rhythm and pattern: emerging concepts. AB - We present three hypotheses related to the nervous system control of breathing in mammals: 1) that neural mechanisms controlling breathing change with state and that the relationship between mechanisms in different states can be described in terms of either modulation or a basic transformation of properties, or both; 2) that the mechanisms generating respiratory rhythm and pattern are separate; and 3) that conditional pacemaker cell activity is the basis for respiratory rhythm in highly reduced states. PMID- 2240273 TI - Chemoreceptor modulation of endogenous respiratory rhythms in vertebrates. AB - The relative contributions of O2- and CO2-sensitive chemoreceptor information to centrally generated respiratory patterns have changed dramatically during vertebrate evolution. Chemoafferent input from branchial O2 chemoreceptors modulates centrally generated respiratory patterns but is not critical for respiratory rhythmogenesis in fishes. In air-breathing fishes, branchial O2 chemoreceptors monitoring internal and external stimuli control the relative contributions of the gills and air-breathing organ to net ventilation, and chemoafferent input is necessary for initiating air breathing. In the transition from water to air breathing by amphibious vertebrates, rhythmic patterns of branchial ventilation are completely replaced by arrhythmic and intermittent patterns of air breathing, and there is progressive dependence on CO2 as a source of respiratory drive. Periodic initiation of air breathing in resting animals appears to depend on attaining a threshold level of afferent activity from O2- and CO2/pH-sensitive chemoreceptors, since hyperoxia and/or hypocapnia can abolish air breathing in all air-breathing vertebrates. Conversely, chemoreceptor stimulation in amphibians and reptiles converts intermittent to more continuous air breathing patterns, suggesting that adequate biasing input from chemoreceptors activates a central rhythm generator. Chemoafferent input in homeotherms serves as one of several sources of drive for rhythmic breathing and supplies feedback for blood gas homeostasis in the face of metabolic or environmental change. PMID- 2240274 TI - Mechanoreceptor modulation of endogenous respiratory rhythms in vertebrates. AB - While pulmonary mechanoreceptors appear to play little or no role in determining the eupneic breathing pattern in some species of vertebrates, they do in others as well as in all species under conditions of elevated respiratory drive. Tonic and phasic inputs from this receptor group have independent roles in determining breathing pattern. Thus withholding lung inflation produces very different results from receptor denervation. There are at least five phases to the respiratory cycle that appear to be under separate control. Tonic receptor input is involved primarily in regulating the length of the respiratory pause, which can occur at the end of inspiration or expiration, depending on the species. Phasic receptor input has different effects during different phases of the cycle as well as different effects at different times during a single phase. This activity contributes to phase switching during the ventilation cycle and thus to the regulation of breathing frequency and tidal volume. The significance of the modulatory effects of phasic input on the duration of different phases of the ventilation cycle is not totally clear, but the evidence suggests that phasic input acts to stabilize the respiratory pattern and may be instrumental in optimizing the breathing pattern in terms of ergometric costs. This appears to be the case in all vertebrate classes, despite dramatic differences in the mechanical events associated with ventilation arising from different respiratory pumps. These receptors also appear to have significant roles other than those associated with modulation of respiratory rhythm, particularly in lower vertebrates. Many of these roles, such as maintaining the integrity of the gill curtain in fish or buoyancy control and regulation of blood flow distribution in reptiles, may be as important as their role in modulating the endogenous rhythm. PMID- 2240275 TI - Receptor interactions in modulating ventilatory activity. AB - The ventilatory control system utilizes a variety of sensory receptor groups, including chemoreceptors and mechanoreceptors, to provide feedback concerning the status of controlled variables. Most ventilatory responses to altered receptor inputs generally involve a complex interaction between several receptor groups, central integrative mechanisms, and other modulatory inputs (e.g., "state," hormonal, or neurotransmitter status). Because the control system is complex, nonlinear, and dynamic, the ultimate ventilatory response elicited by a given stimulus is not easy to predict based on the reflex effects of individual receptor groups studied in isolation. A full understanding of the role that sensory receptors play in ventilatory control requires information concerning interactions among receptor groups and with other elements of the control system. The complexity of the problem and the lack of a uniform definition of the term "interaction" has hindered research in this area. An interaction is defined as a nonadditive relationship between independent inputs to the system. Within this definition, five domains of interaction are described. 1) Algebraic interactions occur in ventilation and/or its components because of their multiplicative and nonlinear relationship. 2) Closed-loop interactions occur because of the prevalence of feedback loops within the respiratory control system. 3) Neural interactions reflect central nervous system integration of simultaneous receptor inputs and are demonstrated when feedback loops are opened. Three subdomains of neural interactions are defined: modulatory, dynamic, and range-specific neural interactions. 4) Mechanical interactions result from nonlinear transformations of motoneuron output into mechanical actions. 5) Adaptive interactions occur when paired receptor or modulatory inputs alter future responses. To understand the role of any sensory receptor group in ventilatory control, it is necessary to define its interactions with other control system elements in each of these domains. Understanding the mechanisms of these interactions requires detailed information about the physical system subserving ventilatory control (mechanics and gas exchange) and the relevant properties of the neural network coordinating their actions. PMID- 2240276 TI - Circadian rhythm in recognition threshold of salt taste in healthy subjects. AB - The circadian rhythm in recognition threshold of salt taste was examined in six healthy young subjects. Plasma aldosterone (PA) and cortisol concentrations, plasma renin activity (PRA), salivary sodium concentration, and salt recognition thresholds were measured every 3 h for a 24-h period. The salt recognition threshold and salivary sodium concentration exhibited similar circadian rhythms, with the lowest values recorded in the afternoon. Positive correlations were observed between the recognition threshold and salivary sodium (P less than 0.001) and between cortisol and PA (P less than 0.001). There was no correlation between PRA and PA. A negative correlation was observed between PA and salivary sodium concentration (P less than 0.01). These data indicate that the recognition threshold for salt taste has a circadian rhythm in young healthy subjects. This rhythm appears to be related to daily variations in the plasma aldosterone concentration and its subsequent effects on salivary sodium concentration. PMID- 2240277 TI - Net basolateral potassium flux and short-circuit current in ouabain-treated frog skin. AB - A new technique has been developed to correlate K loss from cells (JK) across the basolateral membrane into a K-free ouabain Ringer solution and short-circuit current (Isc) for a model Na-transporting epithelium, the frog skin. Distinct differences were observed when the tissue was bathed in sulfate or chloride Ringer. In sulfate Ringer, K-free ouabain treatment caused both JK and Isc to decline in a nearly parallel fashion with time. JK-Isc was approximately 1 microA/cm2. In sulfate Ringer, isoproterenol caused parallel increases, whereas amiloride (apical side) caused parallel decreases in JK and Isc. In chloride Ringer, K-free ouabain treatment caused Isc to decline at a slightly faster rate than JK.JK-Isc was approximately 8 microA/cm2. Bumetanide decreased JK with very little effect on Isc. Barium caused small parallel changes in both Isc and JK. Amiloride decreased Isc with very little effect on JK. These experiments show that after ouabain treatment changes in JK from the cells across the basolateral membrane can largely account for changes in Isc. However, JK also occurs via neutral mechanisms and perhaps from cells not related to the transport pathway, demonstrating that there is not always a tight coupling of K loss at the basolateral membrane with Na entry across the apical membrane. PMID- 2240278 TI - Neurons controlling cardiovascular responses to emotion are located in lateral hypothalamus-perifornical region. AB - We did four experiments to determine whether the lateral hypothalamus perifornical (LH/PF) region is the source of neuronal cell bodies responsible for producing the cardiovascular (CV) responses associated with emotion or the defense reaction. Of particular concern was whether the paraventricular nucleus (PVN) plays a role in the generation of these CV responses. Mapping the hypothalamus with electrical stimulation showed that the CV pattern of responses was never produced by stimulating the PVN and was invariably produced by stimulating the LH/PF region. Complete electrolytic destruction of the PVN and subsequent axonal degeneration did not change the CV pattern of responses elicited by LH/PF stimulation, whereas any encroachment of the lesion on the LH/PF region decreased the magnitude of the CV responses. Injection of the neuroexcitotoxin ibotenic acid (Ibo) into the PVN did not affect responses to LH/PF stimulation, whereas Ibo injection into the LH/PF region eliminated or severely attenuated the CV responses. Retrograde labeling of cells from the thoracic cord and the ventrolateral reticular formation revealed a scattered group of cells in the LH/PF region that may be the cells controlling the CV responses. These results point directly to the LH/PF region as the source of the cell bodies responsible for the autonomic responses associated with emotion or defense reactions. PMID- 2240279 TI - Baroreflex sensitivity in the canine model of obesity-induced hypertension. AB - Studies have demonstrated abnormalities in baroreflex function in various models of hypertension. The purpose of this study was to examine baroreflex sensitivity in the canine model of obesity-induced hypertension. Baroreflex sensitivity was determined by the relative changes in heart rate (HR) in response to changes in mean arterial pressure (MAP) induced by sodium nitroprusside (Nitro) and phenylephrine (Pe). Studies were performed in conscious lean dogs (n = 10) and obese dogs fed a high-fat diet for 6 wk (n = 8). Body weight averaged 18.1 +/- 0.3 kg in the lean dogs and 26.5 +/- 0.5 kg in the obese dogs. Associated with the 46% increase in body weight in the obese dog group were significant increases in MAP (120.7 +/- 3.0 vs. 102.8 +/- 1.5 mmHg) and HR (132.7 +/- 8.5 vs. 96.4 +/- 3.3 beats/min). Administration of Nitro (0.5, 1.0, 5.0 micrograms.kg-1.min-1) resulted in comparable reductions in MAP in the lean and obese dogs. The reflex increases in HR were significantly greater in the obese animals only with a dose of 5.0 micrograms.kg-1.min-1 of Nitro (55.5 +/- 7.7 vs. 32.0 +/- 7.5 beats/min). Administration of Pe (0.5, 1.0, 5.0 micrograms.kg-1.min-1) resulted in significantly greater increases in MAP in the obese dogs (17.8 +/- 4.6 vs. 4.9 +/ 2.6, 37.1 +/- 4.4 vs. 19.6 +/- 2.7, and 72.7 +/- 7.5 vs. 51.5 +/- 7.1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240280 TI - Quantitative genetics of maximal oxygen consumption in a garter snake. AB - Broad-sense heritabilities and genetic correlations of maximal oxygen consumption (VO2max), blood hemoglobin levels, and ventricle mass were estimated in a natural population of snakes. Traits were measured for six or fewer presumed full-sibling offspring from each of 45 wild-caught gravid garter snakes (Thamnophis sirtalis). VO2max was highly reproducible between replicate trial days (r = 0.88). In an attempt to reduce maternal effects, correlations of each character with body mass, snout-vent length, age at testing, litter size, dam mass, and dam snout vent length were removed by computing residuals from multiple-regression equations. These residuals were used in subsequent genetic analyses. Approximate coefficients of variation of residuals were 16% for VO2max, 19% for hemoglobin level, and 13% for ventricle mass. Broad-sense heritabilities were highly significant for all characters [P less than 0.0001; VO2max heritability (h2) = 0.88; hemoglobin level h2 = 0.63; ventricle mass h2 = 0.41], suggesting that they could respond genetically to selection. Phenotypic correlations (rP) among residual characters were significant only between VO2max and ventricle mass (rP = +0.27). VO2max and ventricle mass exhibited a significant (broad-sense) genetic correlation of +0.64; this might facilitate the correlated evolution of these two traits in response to natural or artificial selection. Ventricle mass and hemoglobin level showed a significant environmental correlation of +0.43. Treadmill endurance crawling time (Evolution 42: 335-350, 1988) showed a weak but significantly positive rP with VO2max (rP = +0.17). PMID- 2240281 TI - Induction of plasma inhibitors of interleukin 1 and TNF-alpha activity by endotoxin administration to normal humans. AB - Several naturally occurring inhibitors of interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been demonstrated both in serum and urine of febrile patients. These factors are considered to be part of a regulatory system counteracting potential deleterious effects of the cytokines. We have assayed plasma samples of volunteers who received a bolus intravenous injection of either 4 ng/kg body wt of Escherichia coli endotoxin (n = 6) or 0.9% saline (n = 4) for the presence of IL-1 and TNF-alpha inhibitory activity. Plasma obtained 3 h after endotoxin injection inhibited IL-1-induced PGE2 release from fibroblasts by 57% (P less than 0.001 vs. baseline and saline controls, respectively). Maximal IL-1 inhibitory capacity coincided with fever and tended to disappear with declining body temperature. Normal plasma was found to inhibit TNF-alpha-induced PGE2 release by 20-35%. This inhibitory effect increased to 50-60% in plasma obtained during endotoxinemia. Maximal TNF-alpha inhibitory capacity became detectable when circulating TNF-alpha levels peaked at 120 min after the injection of endotoxin. Our data demonstrate that both IL-1 and TNF-alpha inhibitory activity can be induced experimentally by intravenous endotoxin administration to humans and that their appearance coincides with fever and circulating TNF-alpha levels. PMID- 2240282 TI - Diminished epinephrine response to hypoglycemia despite enlarged adrenal medulla in trained rats. AB - Studies in humans have indicated that trained athletes compared with sedentary subjects have an increased capacity to secrete epinephrine. To investigate whether this is due to an adaptation induced by physical training or a selection phenomenon, rats were swim trained (T) 10 wk for 6 h/day or served as controls being either sedentary freely eating (C), food restricted (FR), sham swim trained (ST), or cold stressed (CS). Adrenal glands were weighted and cross sectioned for light microscopic determination of size of the adrenal medulla. Endurance-trained compared with control rats had heavier adrenal glands (P less than 0.05), higher catecholamine content in the glands (P less than 0.05), and higher adrenal medulla volumes (P less than 0.05) [males: 2.74 +/- 0.16 (T) vs. 2.05 +/- 0.16 (C), 1.90 +/- 0.10 (ST), and 2.21 +/- 0.08 mm3 (CS)] [females: 2.55 +/- 0.11 (T) vs. 1.92 +/- 0.06 mm3 (C)]. Cold stress or sham swim training did not increase adrenal weight or volume of adrenal medulla (P greater than 0.05). To stimulate adrenal medulla secretion, rats had an insulin-induced hypoglycemia. Insulin dose needed to suppress plasma glucose below 4.0 mM was four times greater in sedentary compared with trained rats. During hypoglycemia the epinephrine response was much smaller in trained than in untrained rats (P less than 0.05). In conclusion, in rats strenuous endurance training causes an enlargement of the adrenal medulla. However, possibly reflecting an adaptation within the central nervous system to reduced blood glucose levels induced by repeated exercise bouts, the epinephrine response to insulin-induced hypoglycemia is markedly diminished after training. PMID- 2240284 TI - Modern fictional protagonists: motherless children, fatherless waifs. PMID- 2240283 TI - Dreams and transference. PMID- 2240285 TI - The evolution of schizoid orality. PMID- 2240286 TI - A linguistic model of psychosis--Lacan applied. PMID- 2240287 TI - Dementia, related disorders, and old age: psychodynamic dimensions in diagnosis and treatment. PMID- 2240289 TI - Countertransference and participant observation. PMID- 2240288 TI - Symbiotic recognition: a striving for acknowledgment of self. PMID- 2240290 TI - A brief comment on Freud's attendance at opera performances: 1880-1890. PMID- 2240292 TI - Risk communication and public confidence in health departments. PMID- 2240291 TI - Challenges for public health nutrition in the 1990s. PMID- 2240293 TI - A crisis of community anxiety and mistrust: the Medfly eradication project in Santa Clara County, California, 1981-82. AB - Public anxiety of near panic proportions was created by the announcement of a plan to commence aerial application of malathion bait over a large urban area in California for the eradication of the Mediterranean fruit fly within four days. A risk assessment had reported the project entailed no significant risk to health but environmentalist groups and the media ignored the report. We describe the successful measures taken by State health workers to counteract the anxiety which itself constituted a serious public health problem. The most important measure was the rapid convening of a Health Advisory Committee composed of recognized experts and local professionals and leaders to provide an authoritative, respected and sympathetic voice to deal with the community's concerns. These experiences may be of value to other communities facing unwarranted anxiety over perceived environmental hazards. PMID- 2240294 TI - Modeling the impact of breast-feeding by HIV-infected women on child survival. AB - This study models the survival outcomes of children born to HIV-infected (human immunodeficiency virus) women who are breast-fed, bottle-fed, and wet-nursed. It is estimated that, given the relative risk of alternatives to maternal milk in developing countries, the probability of HIV transmission via breast milk would need to be at least .12 in a community with an under five child mortality rate from non-HIV causes of 100/1000 live births and at least .27 in a community with a rate of 200/1000 before alternative feeding practices should be recommended even to the known HIV-infected mother who has an available feeding alternative with a relative risk of 2:1. While such a low relative risk may be achievable with wet nursing, most studies report a relative risk of at least 3:1 for bottle feeding. A sensitivity analysis is conducted around the relative risk of child mortality from non-HIV causes associated with different feeding practices. While the critical transmission rate does not vary significantly with a rate of false positives as high as 20 percent on the HIV screening test, the critical transmission rate is very sensitive to the availability of HIV screening. In communities where the HIV prevalence rate among mothers reaches 40 percent, breast-feeding should still be recommended in the absence of HIV screening unless HIV transmission via breast milk surpasses 30 percent. PMID- 2240295 TI - Clustering of atherogenic behaviors in coffee drinkers. AB - We studied the clustering of coffee consumption and selected atherogenic behaviors in older adults living in a southern California community. Men were somewhat more likely to drink caffeinated coffee while women were more likely to drink decaffeinated coffee. In men, but not women, caffeinated coffee drinking decreased with age and decaffeinated coffee drinking increased. Caffeinated coffee drinkers drank more alcohol, consumed more dietary saturated fats and cholesterol, were more likely to be current smokers and less likely to be current exercisers than were non-coffee drinkers. Smoking and exercise also showed a dose response relationship to the amount of caffeinated coffee consumed. Risk factor levels among drinkers of decaffeinated coffee were more like those of caffeinated coffee than non-drinkers. These data illustrate the clustering of atherogenic behaviors with coffee drinking and highlight their potential importance in interpreting the growing body of literature about coffee and health. PMID- 2240296 TI - Validation of mothers' reports of dietary intake by four to seven year-old children. AB - The validity of mothers' recall of four to seven year-old children's diet was assessed among 46 first generation Latino immigrant families from the Dominican Republic by comparing intake recalled by the mother to unobtrusive home observations of children. Correlations were moderate to high for calories and for most nutrients. There were no differences in mean intake of total calories or in intake of most macronutrients and micronutrients assessed. At least two-thirds of the children in the lowest (or highest) quintile based on home observations were correctly classified into the lowest or second lowest (or highest) quintiles based on mother's reports for calories and most nutrients. For all food items that were both observed and reported, 51 percent of reported portion sizes were equivalent to observed portion sizes, 15.5 percent were smaller, and 33.5 percent were larger. There was fair to good agreement on the number of food items eaten, with the exception of vegetables. Mothers' recall appears to be useful for classifying children by intake of calories, macronutrients and micronutrients, but provides a somewhat less accurate measure of actual foods eaten, portion sizes, and nutrient levels consumed. PMID- 2240297 TI - Development and validation of a food use checklist for evaluation of community nutrition interventions. AB - We developed a new dietary assessment instrument, the Food Behavior Checklist (FBC), which measures food use related to adopting lower-fat and higher-fiber diets. The FBC is a simplification of the 24-hour diet recall that consists of 19 simple yes/no questions about foods consumed during the previous day. To develop the FBC, an expert committee generated a list of foods based on our intervention program, and we used focus groups and random-digit dialing pretests to refine the format and clarify items. To validate the FBC, we compared responses of 96 women on the FBC to information collected during a professionally administered 24-hour diet recall. For most items, agreement between the FBC and 24-hour recall, based on the kappa statistic, was good to excellent. Agreement was poor for items requiring detailed knowledge about food composition (e.g. high-fiber cereal). There was a trend to over-report general food categories (e.g. luncheon meats) but not specific food items (e.g. ice cream). In an embedded randomized study, we found that a set of introductory items designed to serve as a memory retrieval cue did not improve agreement between the FBC and 24-hour recall. These data provide preliminary evidence supporting the use of short checklist questionnaires on the previous day's food use as a means to assess diet at the group or community level. This relatively inexpensive and rapid measure can be used to inform the design of public health nutrition programs and as an evaluation tool in intervention research. PMID- 2240299 TI - Depressive mood, the single-parent home, and adolescent cigarette smoking. AB - The association between depressive mood and cigarette smoking among adolescents was examined within a multivariate model. Subjects were 205 eleventh graders (123 boys and 82 girls) enrolled in a Northeast metropolitan public high school for science-oriented students. Logistic regression analysis showed an independent relation of depressive mood, friends' smoking behavior, and living in a single parent home with cigarette smoking. Depression scores correlated with the number of cigarettes smoked. These associations suggest that depressive mood and stress may contribute to the onset of smoking. PMID- 2240298 TI - Food and nutrient intake differences between smokers and non-smokers in the US. AB - Data from the Second National Health and Nutrition Examination Survey were analyzed to determine food and nutrient intake differences between current smokers (also categorized as light, moderate, and heavy smokers) and non-smokers. Smokers in several age-race-sex categories have lower intakes of vitamin C, folate, fiber, and vitamin A than non-smokers, and intake tended to decrease as cigarette consumption increased, particularly for vitamin C, fiber, and folate. Smokers were less likely to have consumed vegetables, fruits (particularly fruits and vegetables high in vitamins C and A), high fiber grains, low fat milk, and vitamin and mineral supplements than non-smokers. A negative linear trend was found between smoking intensity and intake of several categories of fruits and vegetables. These data suggest that the high cancer risk associated with smoking is compounded by somewhat lower intake of nutrients and foods which are thought to be cancer protective. PMID- 2240300 TI - Effects of individually motivating smoking cessation in male blue collar workers. AB - Adverse demonstrable health effects linked to the individual's smoking were shown to 2,689 American workers to motivate cessation during routine examinations to detect asbestosis. This intervention was evaluated six to 25 months later by a mailed questionnaire and by telephone to non-responders. Results were compared to yearly quit rates of 2.5 percent to 5 percent for 736 workers who were ex-smokers at the initial examination. Of the 504 men who responded by mail, 29.8 percent had quit smoking, 35.9 percent had cut down from a mean of 28 to 13 cigarettes per day, and 34.3 percent were smoking as before. Subsequent follow-up at one year showed that 25.6 percent remained quit, and that 23 percent of those who cut down had quit, for an overall quit rate of 34 percent. Of 101 non-responders contacted by telephone, 17 percent had quit and 53 percent had reduced smoking. In both samples, those who quit were more likely to have had lower alveolar carbon monoxide (COa) levels, to be older, and to have had asbestosis. Responders by mail were the same age as non-responders but had smoked longer, had higher prevalences of asbestosis, emphysema, chronic bronchitis and higher COa. Demonstration of the adverse personal effects of smoking appear to have contributed to the quit rates or reduced smoking rates in 65 percent of the responding workers. PMID- 2240301 TI - Epidemiologic differences between chlamydia and gonorrhea. AB - To assess the prevalence, demographics, and transmission patterns of genital chlamydia infection, we screened 3,078 patients, and compared identified cases (N = 511) to gonorrhea cases (N = 291) diagnosed in the same setting. Chlamydia cases were younger and more likely to be White than their gonorrhea counterparts. Chlamydia cases were distributed diffusely; geographic overlap between the two diseases was only about 40 percent. Gonococcal coinfection was noted in less than 10 percent of patients with chlamydia. Nearly half of men with chlamydia and four fifths of women were asymptomatic and most cases were identified through screening or contact tracing. Populations at high risk for chlamydia are seemingly different from those for gonorrhea. Differences may be due to control interventions (active for gonorrhea, passive for chlamydia). Chlamydia case reporting and control initiatives are recommended. PMID- 2240302 TI - A small area simulation approach to determining excess variation in dental procedure rates. AB - All small area analyses need to compare the observed variability in rates to that expected by chance alone, but the expected variability is usually not known. This paper uses patient-level data for five dental procedures to simulate the distributions of the summary statistics that are usually generated in such studies. These statistics are found to vary greatly even under the "null hypothesis" that all dentists are using procedures at the same rates. The simulated dentist rates are compared to observed rates obtained in a different study. These findings illustrate problems that can occur in small area analysis studies, and emphasize the importance of using statistical techniques that are appropriate for the data that are to be analyzed. Investigators should make every effort to obtain patient-level data, or at least to understand the underlying distribution of the number of procedures per patient, to avoid mistaking significant deviations from an incorrect model as evidence for significant variation among small areas. PMID- 2240303 TI - Medical and psychosocial factors predictive of psychotropic drug use in elderly patients. AB - The purpose of this study was to investigate medical and psychosocial factors that may be used to identify patients at risk of psychotropic drug use. Population-based surveys were completed by 278 elderly health maintenance organization (HMO) patients in August 1984. Physical and mental health status and social support were measured in the survey. Automated prescription records from the year prior to and the year after the survey were linked to data from the survey. Patients received 737 prescriptions for psychotropic drugs during the two year period under study. Doxepin (20.2 percent), flurazepam (15.2 percent), and diazepam (14.8 percent) were dispensed most frequently. Nearly 30 percent of the patients received a prescription for at least one psychotropic drug during the two-year period, and 14 percent received at least one prescription during both years. Three significant predictors of subsequent psychotropic drug use were: prior use (odds ratio = 17.2, 95% CI = 6.25, 47.33), the number of physical impairments (OR = 1.73, 95% CI = 1.05, 2.84), and the respondent's rating on the Alameda Health Scale (OR = 1.65, 95% CI = 0.99, 2.75). Patients' self-reported mental health status and sociodemographic characteristics were not significant predictors of subsequent use. PMID- 2240304 TI - The association between Type A behavior and change in coronary risk factors among young adults. AB - The association of Type A/B behavior pattern and changes in blood pressure, total serum cholesterol, serum triglyceride, body mass, and smoking was estimated in a cohort of 375 young Black and White men and women from a rural county in Central Kentucky between 1978-79 and 1985-88. Type A participants experienced significant increases in systolic (2.90 +/- 1.29 mmHg) and diastolic (3.80 +/- 1.17 mmHg) blood pressure and in cigarette smoking (3.26 +/- 0.89 cigarettes per day) over the eight-year follow-up period, but Type B participants experienced no change. Type A and B individuals showed similar changes in total serum cholesterol, serum triglyceride, or body mass. Differences between behavioral types in blood pressure were present for women but not men, and for Blacks but not for Whites. These findings suggest a possible significance of the Type A pattern for the development of cardiovascular risk of young adults. PMID- 2240305 TI - Behavioral covariates of waist-to-hip ratio in Rancho Bernardo. AB - We examined lifestyle and dietary habits in 685 men and 943 women (mean age 67 years) who completed an interview, examination, and food frequency questionnaire in 1984-87. Waist-to-hip ratio increased with age and body mass index in both men and women. In multiple regression, waist-to-hip ratio was independently associated with smoking, alcohol consumption, and exercise in men, and with smoking and alcohol consumption in women. The data suggest that waist-to-hip ratio is affected, at least in part, by behavioral, and potentially modifiable, factors. PMID- 2240306 TI - The Framingham Disability Study: relationship of various coronary heart disease manifestations to disability in older persons living in the community. AB - The relation between coronary heart disease and disability was examined in 2,576 community-dwelling women and men ages 55-88 years. These Framingham Study participants were originally recruited in 1948-51 for an examination of cardiovascular disease. Twenty-seven years later, remaining members of the cohort were interviewed to ascertain physical abilities, and a score on a disability scale was assigned. Multivariate logistic analyses examined disability in relation to uncomplicated angina pectoris (AP), complicated AP, and coronary heart disease other than AP, controlling for possible confounders. In younger and older women and men, uncomplicated and complicated AP were associated with disability. Coronary heart disease other than AP was associated with disability only in the younger men. Congestive heart failure predicted disability only in the women. These results suggest that onset of AP should be recognized as a critical point in the development of disability and that AP is a better predictor of disability than is myocardial infarction or coronary insufficiency. PMID- 2240307 TI - The effects of psychosocial work organization on patterns of cigarette smoking among male chemical plant employees. AB - We tested the hypothesis that job strain (the combination of high psychological job demands and low work control) is positively associated with smoking prevalence and intensity in a study group of 389 males employed in a chemical plant, using a self-administered questionnaire. In a logistic regression analysis which controlled for a number of sociodemographic factors, job strain was not found to be associated with smoking cessation. However, among smokers, those in higher-strain jobs smoked more heavily than those in lower-strain positions (OR 1.70, 95% CI = 1.10, 2.61) and were more likely to have increased the amount they smoke (OR 3.72, 95% CI = 1.92, 7.17). PMID- 2240309 TI - Use of fat-modified food products to change dietary fat intake of young people. AB - Food purchasing and preparation practices were modified in two boarding high schools to increase the polyunsaturated-to-saturated fat ratio (P/S) of the diet of students by changing food products rather than attempting to change eating behaviors. During years when fat-modified products were served, the P/S of males increased by 75 percent, versus a decrease of 6 percent during control years. For females, P/S increased by 53 percent during intervention years, versus an increase of 6 percent during control years. PMID- 2240308 TI - Garlic-in-oil associated botulism: episode leads to product modification. AB - In February 1989, three cases of botulism occurred in persons who consumed garlic bread made from a garlic-in-oil product. Testing of leftover garlic-in-oil showed it to have a pH of 5.7 and to contain high concentrations of Clostridium botulinum organisms and toxin. This was the second episode of botulism associated with a low acid garlic-in-oil product which needs constant refrigeration. In response, the Food and Drug Administration has taken steps to prevent a recurrence by requiring that microbial inhibitors or acidifying agents be added to such products. PMID- 2240310 TI - Weekly food servings and participation in social programs among low income families. AB - Low income families were interviewed to determine factors related to the number of family food servings per week. A multiple regression model indicated that participation in WIC (supplemental food program for women, infants and children), household size, and number of different income sources were associated with more family food servings per week. Number of food servings per week decreased the last week of the month most often in families with younger members. PMID- 2240311 TI - The buddy volunteer commitment in AIDS care. AB - Buddy volunteers provide crucial assistance to people with HIV-related illnesses. Based on volunteers' self-administered questionnaires, our study describes the nature of buddy work. Volunteers indicated their satisfaction with both personal performance and buddy program administration. Several factors were associated with volunteer satisfaction. This report is a first attempt to describe this special relationship created in response to the human immunodeficiency virus (HIV) epidemic. PMID- 2240312 TI - Epidemiology of reported cases of AIDS in lesbians, United States 1980-89. AB - National surveillance data for reported cases of acquired immunodeficiency syndrome (AIDS) were used to assess demographic characteristics and behavioral risk factors in lesbians. From June 1, 1980 through September 30, 1989, 79 women with AIDS reported sex relations only with a female partner; most of these women (95 percent) were intravenous drug users. Prevention of human immunodeficiency virus (HIV) infection in the lesbian community will require efforts to prevent and reduce intravenous drug use. PMID- 2240313 TI - Prior cesarean delivery in women with secondary tubal infertility. AB - The history of cesarean delivery was evaluated in a population-based case-control study of secondary infertility in King County, Washington. Sixty-one married women diagnosed with secondary infertility due to tubal problems who had a previous viable pregnancy were compared to 343 married women who had a previous viable pregnancy and then had a live birth that was conceived at the same time the infertile women began trying to conceive. The risk of tubal infertility was not substantially elevated in women who had a previous cesarean delivery in the most recent viable pregnancy compared to women with vaginal delivery (odds ratio = 1.2; 95% confidence interval = 0.4, 3.7). PMID- 2240314 TI - A comparison of homeless, community-wide, and selected distressed samples on the CES-Depression Scale. AB - Center for Epidemiological Studies (CES) Depression Scale results for surveys of homeless, community-wide and selected distressed samples are compared. Nearly four times the percentage of homeless fit the criterion for clinical caseness (a score of 16+) compared to the general population (74 to 19 percent). None of the distressed samples exhibited a higher rate except psychiatric patients diagnosed as acutely depressive. High rates of depression have implications for social policies directed toward homelessness. PMID- 2240315 TI - How valid are mammography self-reports? AB - We compared mammography reports in medical records to self-reports obtained during a 1989 telephone interview survey for a sample of 100 women members of a health maintenance organization (HMO) who indicated they had mammograms within the past year and 100 who said they had not had mammograms within the past year. Of the women reporting they had not had mammograms within the past year, none had mammogram reports in the HMO data center. Of the 100 women reporting they had mammograms within the past year, 94 had confirmatory radiology records. PMID- 2240317 TI - Developing AIDS education for women in county WIC clinics. PMID- 2240316 TI - Incidence of bicycle-related injuries in a defined population. AB - Population-based incidence rates for head injuries and total injuries resulting from bicycle crashes were calculated in a Seattle, Washington health maintenance organization population. Overall rates were 163 per 100,000 for all injuries and 42/100,000 for head injuries. Individuals between 5 and 14 years of age are at highest risk for bicycle-related injuries. The data are presented for their potential utility in program planning. PMID- 2240318 TI - The 'Free Dental Day'--a voluntary public health initiative. PMID- 2240319 TI - Pharmacy education about HIV and condoms. PMID- 2240320 TI - Decline in NHSC physicians threatens patient care. PMID- 2240321 TI - Depression, worry, and the incidence of cancer. PMID- 2240322 TI - Maternal stress and depressive symptoms. PMID- 2240324 TI - At last--a view of Hispanic health and nutritional status. PMID- 2240323 TI - The art and science of interpreting survey data. PMID- 2240325 TI - Hypertension prevalence and the status of awareness, treatment, and control in the Hispanic Health and Nutrition Examination Survey (HHANES), 1982-84. AB - The prevalence rates of hypertension among adult (ages 18-74) Mexican Americans, Cuban Americans, and Puerto Ricans were estimated using data from the 1982-84 Hispanic Health and Nutrition Examination Survey (HHANES). Hypertension is defined as diastolic greater than or equal to 90 mm Hg, or systolic greater than or equal to 140 mm Hg, or currently taking antihypertensive medication. Among Mexican Americans in the Southwestern United States, 16.8 percent of the males and 14.1 percent of the females were found to be hypertensive. Among Cuban Americans in Dade County, Florida 22.8 percent of the males and 15.5 percent of the females were hypertensive. Among Puerto Ricans in the New York City area 15.6 percent of the males and 11.5 percent of the females were hypertensive. The age adjusted rates are significantly lower than comparable rates for Whites and Blacks as measured in the second National Health and Nutrition Examination Survey (NHANES II), 1976-80. Control of hypertension in the HHANES populations fall short of the 1990 Objectives for the Nation established by the US Public Health Service 60 percent (34 percent controlled Mexican American hypertensives, 27.8 percent controlled Cuban American hypertensives, and 29 percent controlled Puerto Rican hypertensives. PMID- 2240326 TI - A note on the measurement of hypertension in HHANES. AB - Using data from the HHANES, we found the rates of elevated blood pressure readings on clinical examination to be extremely low for a sample of Mexican American and Puerto Rican women. The prevalence rates were one-fourth to one fifth the rates found for a comparable sample of White women from NHANESII. These findings are discrepant with the little that is known about hypertension prevalence among Hispanics and with estimates of hypertension prevalence for Mexican Americans and Puerto Ricans drawn from NHANESII. While our HHANES samples women had much lower rates of clinical high blood pressure than Whites, they reported hypertension histories in excess of Whites. Rates of medicine usage among Hispanics were insufficiently large for effective treatment to explain the disparity. The prevalence estimates increased, but the relative discrepancies remained when we altered our sample specifications and clinical high blood pressure measure. A possible explanation for these discrepancies is that few physicians performed the majority of blood pressure readings in our HHANES sample. This may have been statistically inefficient. The discrepancies noted suggest that HHANES may not be a reliable source of information on hypertension among Hispanic women. PMID- 2240328 TI - Executive women and health: perceptions and practices. AB - The purpose of this study was to obtain a socioeconomic/health profile of a select group of executive women, to understand more about their personal and professional lives, and to examine how these factors relate to their overall health. The data were obtained from a self-administered 73-item questionnaire that was mailed during spring 1987 to the 1,000 members of a professional executive women's organization with 15 chapters across the United States. Findings suggest that the women in executive positions do not necessarily compromise their health. In comparison with a group of age/gender/education matched working women, the overall wellness and risk assessment scores were remarkably similar. The study group, however, reported greater life satisfaction, stronger social support, and excellent health status; the overwhelming majority was satisfied with their personal and professional lives and believed that they were in control of both. This perception, coupled with the relatively high wellness scores, suggests that on average this group of executives may be in better health than had been predicted as women rose to executive positions within organizations. PMID- 2240327 TI - Fruit and vegetables in the American diet: data from the NHANES II survey. AB - Twenty-four hour dietary recall data from the Second National Health and Nutrition Examination Survey (1976-80) were used to estimate the numbers of servings of fruit and vegetables consumed by Black and White adults, to examine the types of servings (e.g., potatoes, garden vegetables, fruit, and juice), and to estimate the mean intake of calories, fat, dietary fiber, and vitamins A and C by number of servings. An estimated 45 percent of the population had no servings of fruit or juice and 22 percent had no servings of a vegetable on the recall day. Only 27 percent consumed the three or more servings of vegetables and 29 percent had the two or more servings of fruit recommended by the US Departments of Agriculture and of Health and Human Services; 9 percent had both. Consumption was lower among Blacks than Whites. The choice of vegetables lacked variety. Diets including at least three servings of vegetables and two servings of fruit contained about 17 grams of dietary fiber. Although caloric and fat intake increased with increasing servings of fruit and vegetables, the percent of calories from fat remained relatively constant. Although these data are 10 years old, more recent surveys have shown similar results. The discrepancy between dietary guidelines and the actual diet suggests a need for extensive public education. PMID- 2240329 TI - Day care characteristics associated with Haemophilus influenzae disease. Haemophilus influenzae Study Group. AB - To identify characteristics of day care facilities associated with H. influenzae disease, we compared 92 licensed facilities in which a case of H. influenzae disease had occurred with randomly selected facilities at which no cases occurred. Matched univariate analysis showed that personnel at facilities where H. influenzae disease occurred were more likely than those at control facilities to use towels or handkerchiefs to wipe children's noses, admit children who were not toilet trained or had diarrhea ("liberal fecal policy"), had a narrower age range, were more likely than control facilities to be for-profit and less likely to use volunteers. In a multivariate model that adjusted for age range, profit status and liberal fecal policy, towel or handkerchief use (OR 5.5, 95% CI: 1.1, 30) was the only variable independently associated with case facilities. This is the first association of a specific day care practice with H. influenzae disease. PMID- 2240330 TI - Injury and disability in matched men's and women's intercollegiate sports. AB - Eight matched men's and women's intercollegiate varsity teams were studied prospectively for one academic year to determine the incidence of athletic injury and resulting disability. Sports in which both men and women participated in a comparable manner were chosen: basketball, fencing, gymnastics, swimming, tennis, indoor track, outdoor track, and volleyball. Men (232) and women (150) were injured at comparable rates, 42 percent versus 39 percent. When adjusted for exposure time, seven of the eight sports continued to show similar injury rates. Women gymnasts, however, experienced .82 injuries per 100 person-hours of exposure as compared to .21 injuries for the men (p = .0001). Disability was greater in women gymnasts, 7.44 days per 100 person-hours versus 1.15 days for men (p = .0004). Percent of season lost to injury was also greater for women gymnasts. Types and sites of injury were similar for men and women, with sprains and strains accounting for over half of all injuries. We found no evidence for gender differences in matched sports except for gymnastics, in which technically diverse events may have accounted for the differences observed. PMID- 2240331 TI - Coding external causes of injury (E-codes) in Maryland hospital discharges 1979 88: a statewide study to explore the uncoded population. AB - We examined the trends in hospital discharge E-coding in Maryland over a 10-year period. The overall proportion of E-coded discharges has increased from 40 percent in 1979 to 55 percent in 1988. E-coding was lower in the severely injured, the elderly, and patients with long hospital stays. Our findings demonstrate that E-code reporting varies because of the limited number of data fields available for coding of discharge diagnoses. Universal, systematic reporting of E-codes in hospital discharge data is essential if these data are to provide critically needed information about nonfatal injuries. Hospital discharge data formats should contain separate fields for E-codes and the use of these codes, we believe, should be mandated. PMID- 2240332 TI - A case-control study of the effectiveness of bicycle safety helmets in preventing facial injury. AB - In a case-control study we sought to assess the potential effectiveness of helmets in preventing facial injuries. Our study included 212 bicyclists with facial injuries and 319 controls with injuries to other body areas, who were treated in emergency rooms of five Seattle area hospitals over a one-year period. Using regression analyses to control for age, sex, education and income, accident severity, and cycling experience we found no definite effect of helmets on the risk of serious facial injury (odds ratio 0.81; 95 percent confidence interval = 0.45, 1.5), but protection against serious injuries to the upper face (odds ratio 0.27; 95% CI = 0.1, 0.8). No protection was found against serious injuries to the lower face. The independent effect of helmet use on facial injury was difficult to isolate due to the association of head and facial injuries. Our results suggest that bicycle helmets as presently designed may have some protective effect against serious upper facial injuries. PMID- 2240333 TI - Association of hepatitis B surface antigen and core antibody with acquisition and manifestations of human immunodeficiency virus type 1 (HIV-1) infection. AB - We examined the associations between seropositivity for hepatitis B virus (HBV) with the presence or development of antibodies to human immunodeficiency virus (HIV-1) and with HIV-1 induced T-helper lymphocyte deficiency or acquired immunodeficiency syndrome (AIDS). Serologic data on HBV and HIV-1, cytometric enumeration of CD4+ lymphocytes, clinical events (AIDS by Centers for Disease Control criteria) and hepatitis B vaccination histories were available on 4,498 homosexual participants in the Multicenter AIDS Cohort Study, Men were classified as to previous infection with HBV and prevalent or incident infection with HIV-1. Although there was an association between seropositivity for HBV infection and HIV-1 infection at enrollment (odds ratios anti-HBc 2.6; HBsAg 4.2), the relation between HBV seropositivity and subsequent seroconversion to HIV-1 was weaker (odds ratios 1.3 and 1.6). HIV-1 seroconversion was also associated with a history of certain other sexually transmitted diseases, but predisposing sexual practices did not account for the association between HBV and HIV-1 infection. Seropositivity for HBV infection at entry was not related to initially low or more rapid subsequent decline in T-helper lymphocyte counts and was not associated with an increased incidence of AIDS during 2.5 years of follow-up. History of vaccination against HBV did not appear to decrease susceptibility to HIV-1 infection or to subsequent progression of immunodeficiency. We conclude that prior HBV infection is unlikely to be specifically associated with acquisition of HIV-1 infection and is unrelated to more rapid progression of HIV 1-induced immunodeficiency. PMID- 2240334 TI - Death in prison: changing mortality patterns among male prisoners in Maryland, 1979-87. AB - The leading causes of death (rate per 100,000 prisoner-years) in Maryland state prisons for the period 1979-87 were circulatory system disease (59), suicide (40), and homicide and legal intervention (30). Acquired immunodeficiency syndrome (AIDS) became the leading cause of death in 1987. Homicides declined after 1980; drug overdose deaths peaked in 1981 and later disappeared. Male inmates have 39 percent lower all-cause death rates than the general population of Maryland after adjustment for age and race. PMID- 2240335 TI - Long-term impact of smoking cessation on the incidence of coronary heart disease. AB - Using a simulation model of the US male population, we estimated the long-term impact that future smoking cessation programs would have on the distribution and occurrence of coronary heart disease in males ages 35-84. For interventions that reduce the number of smokers by 25 percent in 1990, the number of men free of coronary heart disease is projected to increase by 416,787 (0.7 percent) in 2015, and the age-standardized absolute incidence to decline by 2.3 percent. Incidence rates and absolute incidences are projected to fall in men under age 65, but absolute incidence would rise in men over age 65, in large part because of the increased number of men who were at risk for coronary heart disease because of a reduction in non-coronary smoking-related mortality. These trends were more marked for greater smoking reductions and were generally unaffected in a variety of analyses using alternative assumptions, which considered smoking as a risk factor in the elderly, a lag-time before benefits from smoking cessation were realized and secular declines in smoking prevalence. Subject to the assumptions of our model, we conclude that smoking reductions will markedly reduce coronary heart disease, especially in younger age groups, and that this benefit will be slightly offset by a small increase in absolute incidence in elderly men. PMID- 2240336 TI - Overcoming potential pitfalls in the use of Medicare data for epidemiologic research. AB - We used Medicare data bases and US Census data to address two questions critical to the use of Medicare files for epidemiologic research. First, we examined the degree to which the population enrolled in the Medicare program is similar to the elderly resident population of the United States, as estimated by the US Census. We found small differences in the total population estimates but substantial differences by age and race. Second, we found that among Medicare enrollees, physician claims identify a small proportion of hip fracture cases which are not documented in the hospital discharge files. This proportion varies by age, region, and state within the United States. Calculation of rates based on Medicare hospital discharge data, and probably other hospital discharge data sets as well, must take these limitations into account. Use of all available Medicare data files can overcome these limitations. PMID- 2240337 TI - Prospective payment and the utilization of physical therapy service in the hospitalized elderly. AB - We studied the effect, in a university teaching hospital, of the prospective payment system (PPS) on utilization of physical therapy (PT), a non-reimbursable service; subjects were hospitalized patients aged 75 or older with non-PT-related diagnoses (myocardial infarction, pneumonia, congestive heart failure, and colectomy) and PT-related diagnoses (cerebrovascular accident and hip fracture). The proportion of patients referred for PT increased from 68 percent pre-PPS to 85 percent post-PPS for those with PT-related diagnoses and from 13 percent pre PPS to 19 percent post-PPS for those with non-PT-related diagnoses. The mean number of sessions of PT decreased slightly for both groups: from 8.5 to 7.6 sessions for those with PT-related diagnoses and from 5.2 to 4.5 for those with non-PT-related diagnoses. In patients with PT-related diagnoses whose ambulatory status worsened during hospitalization, referrals for PT increased from 76 percent pre-PPS to 98 percent post-PPS. Referrals of comparable patients with non PT-related diagnoses did not increase. Changes in provider education and efforts to reduce length of stay may account for these findings. PMID- 2240338 TI - Prevalence of chronic bronchitis among US Hispanics from the Hispanic Health and Nutrition Examination Survey, 1982-84. AB - In the Hispanic Health and Nutrition Examination Survey (HHANES), Puerto Ricans had a higher age-adjusted prevalence of self-reported chronic bronchitis (2.9 percent, 95% CI = 2.2, 3.6) than Mexican Americans (1.7 percent, 95% CI = 1.3, 2.1) or Cubans (1.7 percent, 95% CI = 0.9, 2.5). The prevalence of chronic bronchitis was at least 2 times higher in smokers as compared to nonsmokers among Puerto Ricans and Cubans, but not for Mexican Americans. PMID- 2240339 TI - Prevalence and restrictiveness of smoking policies in King County, Washington, manufacturing worksites. AB - This study examined prevalence of smoking policies and of significant smoking restrictions in a 1988 random sample of 1,528 manufacturing companies in the Seattle, Washington area, and related these characteristics to worksite size and industry type. Sixty-nine percent of companies had formal smoking policies and 85 percent regulated smoking to some degree. Workforce size was directly related to prevalence of significant smoking restrictions, but when type of industry was controlled, the linear trend in the size/prevalence relationship was sustained in only three of the 18 industry groupings. PMID- 2240340 TI - Depressive symptoms and cigarette smoking among Latinos in San Francisco. AB - We administered the Center for Epidemiological Studies Depression (CES-D) Scale to 547 San Francisco Latinos as part of a random digit dialing telephone survey to evaluate smoking behavior. Both men and women current smokers had the highest mean CES-D levels (9.7 and 14.3, respectively). Logistic regression analysis adjusting for gender, acculturation, education, age, and employment showed that current smokers had an odds ratio of 1.7 (95% CI = 1.3, 2.2) for significant depressive symptoms compared to former smokers (OR = 1.1;95% CI = .8, 1.6) and never smokers (OR = 1). PMID- 2240341 TI - Dental office practices for tobacco users: independent practice and HMO clinics. AB - Surveys of independent dental practitioners and health maintenance organization (HMO) dentists and their adult male patients in Oregon found that cessation information and advice was being given to tobacco-using patients, especially smokeless tobacco users, and that the tobacco users surveyed expressed interest in obtaining help to quit. Oral health providers expressed an interest in further training in how to help their tobacco-using patients to quit. PMID- 2240342 TI - Evidence for gonococcal transmission within a correctional system. AB - In a study to examine sexually transmissible disease occurring within a large correctional system where sexual activity is prohibited, 27 male inmates acquired culture-proven gonorrhea from in-jail sexual activity during a three-month period. These results provide evidence to encourage inmate education about the acquired immunodeficiency syndrome (AIDS) and to support condom distribution programs in correctional facilities. PMID- 2240343 TI - HIV seroconversion in two homosexual men after receptive oral intercourse with ejaculation: implications for counseling concerning safe sexual practices. AB - Seroconversion for HIV antibody occurred in two homosexual men who reported no anal intercourse for greater than or equal to 5 years and multiple episodes of receptive oral intercourse with ejaculation. Neither man reported intravenous drug use or receipt of blood products. The last antibody-negative specimen was also negative by the polymerase chain reaction and p24 antigen assays. All sexually active persons should be clearly counselled that receptive oral intercourse with ejaculation carries a potential risk of HIV transmission. PMID- 2240344 TI - The AIDS-related experiences and practices of primary care physicians in Los Angeles: 1984-89. AB - Telephone interviews of random samples of Los Angeles primary care physicians in 1984, 1986, and 1989 obtained information about their AIDS-related practice experiences, and sexual history taking. Data from mid-1989 reveal almost 74 percent have worked up at least one patient for AIDS or HIV infection in the past six months and 39.5 percent are caring for at least one patient with AIDS or AIDS related complex. Self-reported use of appropriate sexual history questions has improved substantially over this five-year period. PMID- 2240345 TI - Behavioral change in longitudinal studies: adoption of condom use by homosexual/bisexual men. AB - We compared reporting serial cross-sectional prevalence of sexual behavior over time, to reporting individual patterns of behavioral change in a cohort of homosexual men at a six-month interval. Aggregate prevalence rates underestimated the magnitude of change to safer practices, and failed to provide information on relapse to less safe practices. We conclude that it is important to report data based on individual fluctuations in behavior for the evaluation of change over time. PMID- 2240346 TI - Seat belt use in cars with air bags. AB - Seat belt use was observed in 1,628 cars with air bags and manual belts and 34,223 cars with manual seat belts only. Sixty-six percent of drivers in cars with air bags wore seat belts compared to 63 percent of drivers in cars with manual belts only. The study found no evidence for the speculation that drivers with air bags will reduce their seat belt use because they believe an air bag alone provides sufficient protection. PMID- 2240347 TI - Age, sex, and road-use patterns of motor vehicular trauma in Rhode Island: A population-based hospital emergency department study. AB - Population-based hospital emergency department data on motor vehicle traffic trauma in Rhode Island, 1984-85, are analyzed by age, sex, and road-use status. Annualized rates of overall and severe trauma were 1,195 cases (95% confidence interval [CI] = 1,164, 1,225) and 102 cases (95% CI = 94, 111) per 100,000 population, respectively. Overall and severe rates peaked at ages 15-24 years. Male rate excesses were most pronounced for motor-cycle and pedal cycle trauma. PMID- 2240349 TI - Infant care permits: a practical method for raising the quality of infant care within a community. PMID- 2240348 TI - Evaluation of the efficacy and cost effectiveness of health education methods to increase medication adherence among adults with asthma. AB - We randomized 135 adult asthma patients to a control group, and 132 patients to an experimental group which received a special health education intervention. Four adherence measures were documented at baseline and 12-month follow-up: correct inhaler use, inhaler adherence, medication adherence, and total adherence rating. Costs to routinely deliver the intervention were $32.03/patient. Experimental group patients exhibited a significantly higher level of improvement in adherence (44 percent) than control group patients (2 percent). PMID- 2240350 TI - Computerization of annual immunization surveys. PMID- 2240351 TI - Incorporation of pyrazinamide into community-wide treatment of tuberculosis. PMID- 2240352 TI - Dietary vitamin C intake and cigarette smoking. PMID- 2240353 TI - Hispanic health and nutrition examination survey, 1982-84: findings on health status and health care needs. PMID- 2240354 TI - Placental site nodules and plaques. A clinicopathologic analysis of 20 cases. AB - The clinical and pathological features of 20 cases of a nodular or plaquelike trophoblastic lesion at the placental site, which we have designated "placental site nodule or plaque" (PSN-P), are described. The lesions occurred in patients 27 to 45 years of age, and were discovered in an endometrial curettage specimen performed because of menorrhagia or irregular uterine bleeding, or were incidental findings in curettage or hysterectomy specimens. They were grossly visible in five cases. Microscopic examination disclosed single or multiple, mostly well-circumscribed, oval, or plaquelike, variably cellular nodules that were characteristically extensively hyalinized. The lesional cells typically had abundant cytoplasm that was amphophilic, eosinophilic, or occasionally vacuolated, and irregular, often degenerative-appearing nuclei; mitotic figures were absent or rare. Immunohistochemical staining for human placental lactogen was focally positive in all but one specimen stained; most of the lesional cells stained for cytokeratin. An uneventful follow-up of 1 to 7 years was obtained in 14 cases, including five in which the only treatment was dilatation and curettage. The major lesion to be differentiated from the PSN-P is the placental site trophoblastic tumor. Features favoring the former diagnosis include its usually small size, circumscription, extensive hyalinization, degenerative appearance, and mitotic inactivity. These features, as well as the absence of squamous cells, help distinguish PSN-P from the rare hyalinizing squamous cell carcinoma of the cervix. The available evidence indicates that PSN-P is benign. PMID- 2240355 TI - Further phenotypic evidence that nodular, lymphocyte-predominant Hodgkin's disease is a large B-cell lymphoma in evolution. AB - Five cases of nodular, lymphocyte predominant Hodgkin's disease (nLP HD), in which an association with (n = 3) and transformation to (n = 2) large cell lymphoma (LCL) were found, were studied with monoclonal antibodies against B-, T , and Reed-Sternberg (R-S) cell-associated antigens and epithelial membrane antigen (EMA) on paraffin sections. Both lymphocytic (L) and histiocytic (H) cells of nLP HD and lymphoma cells of LCL expressed multiple B-cell-associated antigens (detected by LN-1/CDw75, L26, MB2, DBB.42, DBA.44, DND.53, DNA.7 antibodies) but did not react with antibodies against T-cell-associated (MT1, UCHL1/CD45RO) (one exception for CD45RO in LCL) and R-S cell-associated (Leu M1/CD15, Ber-H2/CD30) antigens. EMA was expressed by L and H cells in all cases and conserved in LCL cells, emphasizing the frequent expression of EMA by the diagnostic cells of nLP HD. An antibody (BNH9) against blood group-related antigens (H and Y oligosaccharide antigens) that does not normally react with lymphoid cells was found to be reactive with few L and H cells in two of five and most LCL cells in four of five cases. The finding might be indicative of abnormal activation of lymphoid cells. The data reinforce current implications that nLP HD is a B-cell malignancy in evolution and that it is not truly representative of Hodgkin's disease in terms of biological and clinical behavior. PMID- 2240356 TI - Uterine lithiasis. AB - We report a case of uterine lithiasis in a 73-year-old Latin American woman. The patient underwent vaginal hysterectomy and colporrhaphy for complaints related to secondary uterine prolapse and cystocele. The 70-g, 8 x 5 x 3.5 cm uterus had a normal shape. Ten white, starlike, 0.5 x 0.5 x 0.2 cm, calcified structures were found within the endometrial cavity. Chemical analysis of one of these by x-ray diffraction showed it to be composed of calcite, one of the crystalline forms of calcium carbonate. To our knowledge, this is the first report of human uterine lithiasis in the literature. PMID- 2240357 TI - Identification of a mislabeled fixed specimen by DNA analysis. AB - Formalin-fixed, paraffin embedded surgical specimens can be identified by genotypic analysis. DNA was extracted from single sections of fixed tissue and amplified by the polymerase chain reaction for the human leukocyte antigen (HLA) DQ alpha and low density lipoprotein receptor genes. These two loci are polymorphic and fixed specimens can be distinguished based on differences between these alleles. The examination can be performed in 2 days and the HLA DQ alpha test utilized a nonisotopic color detection method. In this case report, a mislabeled specimen was identified as a section from a mastectomy because they had identical genotypes. Molecular genetic analysis of the DNA present in fixed specimens can yield information not otherwise evident from the histology. PMID- 2240359 TI - Variations in malaria transmission rates are not related to anopheline survivorship per feeding cycle. AB - Anopheline survivorship, vectorial capacity, and mosquito infection probability estimates from mosquito infection rates were determined 4 times in 1 year in a Papua New Guinea village. Estimates of survivorship over the length of the extrinsic incubation period differed significantly during the year. However, survivorship per feeding cycle, individual mosquito vectorial capacity, and mosquito infection probability did not vary significantly. Estimates of these parameters were then compared to estimates of survivorship, individual vectorial capacity, and mosquito infection probability in mosquito populations in other villages in the study area. Since survivorship per feeding cycle did not vary significantly among the mosquito populations in these villages, changes in malaria transmission potential can be better gauged from estimates of survivorship over the length of the extrinsic incubation period. However, as measurements of relative inoculation rates are easier to perform and have been related to parasite prevalences in children in this area, estimates of inoculation rates are a preferred option for estimating malaria transmission in the Madang area of Papua New Guinea. PMID- 2240358 TI - A distinctive cardiovascular lesion resembling histiocytoid (epithelioid) hemangioma. Evidence suggesting mesothelial participation. AB - This paper presents 14 examples of a distinctive cardiovascular lesion. The patients' ages ranged from 5 to 76 years (mean, 51 years). There were seven male patients and seven female patients. All of the lesions were small and represented incidental surgical findings. Ten were attached to the endocardium, three were free-floating in the pericardial cavity, and one was inside a dissecting aneurysm of the ascending aorta. Microscopically, the lesions were enclosed in a fibrinous network and composed of a solid proliferation of round to polygonal cells with centrally located nuclei. Immunohistochemically, the cells were negative for FVIII-related antigen and lysozyme, but they stained positively for keratin, especially when clustered in small micropapillary or tubule-like formations. The nature and pathogenesis of these lesions are uncertain. Their location and some of their microscopic features originally suggested a relationship with the entity described as histiocytoid (epithelioid) hemangioma. However, their intense immunoreactivity for keratin, occasional presentation in the pericardial sac, and marked morphologic similarities with nodular mesothelial hyperplasia as sometimes seen in hernia sacs point toward the alternative possibility of a reactive mesothelial nature. A possible pathogenetic mechanism for the endocardial cases is ingrowth of pericardial mesothelial cells along a perforation tract that may have developed at the time of a cardiac catheterization. There were no recurrences or metastases in any of the cases. PMID- 2240360 TI - Evaluation of survival potential and malaria susceptibility among different size classes of laboratory-reared Anopheles dirus. AB - Four size classes of Anopheles dirus were reared from different larval densities. Higher densities produced smaller adults with lower survivorship. Larger females took larger bloodmeals by artificial feeding with cultured Plasmodium falciparum and developed significantly more oocysts. PMID- 2240361 TI - Geographical distribution of Plasmodium falciparum erythrocyte rosetting and frequency of rosetting antibodies in human sera. AB - Uninfected erythrocytes bind spontaneously to those infected with certain strains of Plasmodium falciparum. This is known as spontaneous erythrocyte rosetting. We have studied the occurrence and frequency of rosetting in 75 fresh patient isolates and have identified rosetting strains from Africa, South America, and Asia. Rosetting was present in 49% of the isolates tested; the frequency of rosetting red blood cells (RBC) in individual isolates was 0-75% when scored during the first cycle of in vitro growth. Rosetting antibodies were found in 15 out of 73 (21%) Liberian sera as measured by disruption of rosettes in vitro. However, antibodies able to inhibit CD36 dependent cytoadherence of P. falciparum infected RBC were not detected in these sera. Erythrocyte rosetting is a geographically widespread phenomenon. Rosetting antibodies seem to be induced by natural infection and the molecular mechanism of rosette formation seems distinct from that of endothelial cytoadherence. PMID- 2240362 TI - Studies in owl monkeys leading to the development of a synthetic vaccine against the asexual blood stages of Plasmodium falciparum. AB - During the development of a synthetic vaccine for human use against the asexual blood stages of Plasmodium falciparum, monkey trials were performed to assess safety, immunogenicity, and protectivity. We determined the minimal infective dose of the P. falciparum FVO strain, the kinetics of the immune response induced by vaccination with the synthetic peptide mixture (S7 + S12 + S17) or the synthetic hybrid polymeric protein SPf66, and the induction of protective immunity against the experimental challenge with 2 P. falciparum strains. A clear boosting effect was observed, determined by the increased antibody titers against synthetic peptides S7, S12, S17, and SPf66, and by improvement in the protective immune response against the challenge. These studies suggest that either the peptide mixture or the synthetic hybrid polymeric protein are excellent choices for the development of a vaccine against P. falciparum. PMID- 2240364 TI - Genetic analysis of Leishmania mexicana populations from Texas, Latin America, and the Caribbean. AB - A genetic analysis using enzyme data of 72 Leishmania mexicana isolated from hosts in Texas, Latin America, and the Caribbean is presented. All isolates from each country were combined and considered as local populations. Allomorph (allele determined by electrophoresis) frequencies for 20 enzyme (loci) were calculated and 7 populations (Texas, Mexico, Belize, Guatemala, Ecuador [EC], Venezuela, and the Dominican Republic [DR]) were compared pairwise in the statistic of genetic identity (I) (level of genetic similarity). All populations were found to be genetically similar with a mean I value for all comparisons of 0.890 +/- 0.067. When DR was included as one of the pair compared, I = 0.811 +/- 0.034. Among comparisons that include EC (excluding EC vs. DR), I = 0.875 +/- 0.026. The mean I for the other comparisons was less than 0.9. The data indicate that the DR population is divergent enough from the others that it can be considered at the subspecies/incipient species level of evolutionary divergence; the EC population is, to a lesser extent, distinct from the others, and the other 5 represent geographic populations of 1 widely distributed species. A diagrammatic representation of the allomorphs among the 72 isolates is included. There were some allomorph/geographical (or local) population relationships noted. PMID- 2240363 TI - Immunization of owl monkeys with a combination of Plasmodium falciparum asexual blood-stage synthetic peptide antigens. AB - A mixture of 3 synthetic peptides (35.1, 55.1, and 83.1) corresponding to portions of the 35 kDa, 55 kDa, and 83 kDa proteins from the asexual blood stages of Plasmodium falciparum and a polymer of a syntheic peptide incorporating the 3 individual peptides (SPf66) were tested as candidate malaria vaccine antigens in Aotus nancymai. Monkeys were immunized with combinations of the 3 peptides from 2 separate sources (Centers for Disease Control [CDC], Atlanta, GA or Colombia) or with the synthetic polymer. Animals immunized with a combination of the 3 peptides from CDC had higher antibody titers to the 35.1 and 55.1 peptides than to the 83.1 peptide. Monkeys immunized with a combination of the 3 peptides produced in Colombia developed higher levels of antibody to the 55.1 than to the 83.1 and 35.1 peptides. Animals immunized with the polymer produced detectable antibodies to the 55.1 peptide alone. Following challenge with P. falciparum, no differences were observed between the 3 vaccine groups and 2 control groups with respect to the number of animals with parasitemias greater than or equal to 10%. The inconsistency of serologic response to all 3 peptides in these animals contrasted with previous trials performed in Colombia where the monkeys developed high antibody titers against the 3 peptides and were protected against the experimental infection. PMID- 2240365 TI - Ultrasonographical investigations of onchocerciasis in Liberia. AB - The efficiency of ultrasonography (US) for the diagnosis and clinical characterization of onchocerciasis was evaluated. US was performed on 120 probands in Liberia. Ninety-two patients had generalized onchocerciasis, 21 patients suffered from the chronic hyperreactive form of onchocerciasis (sowda), and 7 probands served as controls. Patients were examined by US with linear (7.5 MHz and 5 MHz) and sector (3.5 MHz) scanners. US results were evaluated by examination of extirpated nodules. The US structure of nodules revealed a typical pattern consisting of a homogeneous echogenicity with small echodense particles and a lateral acoustic shadow, and differentiation from lymph nodes, lipoma, or fibroma was achieved. Within the onchocercomata, calcifications or fluid were identified. Regarding the estimation of the worm burden, it is important to note that in 24 patients, additional nodules not previously palpated were found by US. Also, the number of worm centers in palpable conglomerate nodules were determined more exactly by US than by palpation. In 4 of 16 sowda patients, impalpable nodules were found by US. In 13 patients with positive microfilaria counts, no nodules could be detected. The highly characteristic ultrasonographical pattern of onchocercomata may serve as a basis for further US investigations in onchocerciasis. PMID- 2240366 TI - South American blastomycosis: ophthalmic and oculomotor nerve lesions. AB - A case of South American blastomycosis began with an oropharyngeal lesion which was followed by a granulomatous uveitis. The patient was treated with Amphotericin B and showed a clinical regression. Four months later, he developed a right 3rd cranial nerve palsy, aggravating the clinical aspect with a severe generalized involvement of the central nervous system and death. Necropsy showed blastomycotic meningoencephalitis. PMID- 2240367 TI - Recombinant capsular antigen (fraction 1) from Yersinia pestis induces a protective antibody response in BALB/c mice. AB - Yersinia pestis produces a glycoprotein capsule, the biosynthesis of which appears to be temperature dependent. The fraction I (F1) component of this capsule is specific to Y. pestis and the detection of F1 antibodies is the basis for several serological tests. We report the cloning of the F1 gene and its expression in Escherichia coli using the phagemid vector lambda ZAPII and a F1 specific monoclonal antibody. The recombinant F1 antigen had a molecular weight of 17 kDa, which proved to be identical to that of the F1 antigen produced by Y. pestis. The recombinant cells produced F1 antigen at 37 degrees C but only minimal amounts at 27 degrees C, suggesting that the genetic features affected by temperature in Y. pestis may be operating in the E. coli clone. It is not known if their similar molecular weights reflect the glycosylated nature of both proteins. F1 antigen purified from the E. coli recombinant induced a protective immune response in BALB/c mice challenged with up to 10(5) virulent Y. pestis. The resistance of immunized mice to plague infection correlated with high titers of F1 antibody. The cloned gene expresses an immunogenically competent F1 antigen suitable for use in plague serodiagnostics and vaccine development. PMID- 2240368 TI - Infection of colonized cat fleas, Ctenocephalides felis (Bouche), with a rickettsia-like microorganism. AB - We report the ultrastructure of a rickettsia-like microorganism in a colonized population of the cat flea Ctenocephalides felis (Bouche). The microorganism occurs principally in the cytoplasm of midgut cells, but similar microorganisms were detected in the tracheal matrix, muscle, hypodermis, ovaries, and the epithelial sheath of the testes. The microorganism has a well-defined cell membrane consistent with rickettsia and measures 0.25-0.45 microns in diameter with lengths up to 1.5 microns. It was observed repeatedly in fleas of 1 laboratory colony, including newly emerged non-bloodfed specimens, but not in specimens from several other sources. PMID- 2240369 TI - Human T cell lymphotropic virus infection in Guaymi Indians from Panama. AB - Preliminary studies found that 9% of Guaymi Indians from Bocas del Toro province have antibody to human T cell lymphotropic virus (HTLV-I/II). The present study enrolled 317 (21% of the population) Guaymi Indians from Changuinola, the capital of Bocas del Toro province and 333 (70% of the population) from Canquintu, an isolated rural village. Demographic information and family relationships were ascertained and subjects were screened for neurologic diseases. Serum specimens were screened by an enzyme-linked immunosorbent assay for HTLV-I/II antibody and positives were confirmed according to U.S. Public Health Service criteria. Twenty five (8%) Guaymi residing in Changuinola and 7 (2.1%) from Canquintu were confirmed seropositive. In Changuinola, antibody was virtually limited to residents greater than or equal to 15 years of age (24 [16%] of 153) and rates were slightly higher in males than in females; in Canquintu, antibody rates did not increase significantly with age and appeared higher in females than in males. In Changuinola, there was no evidence for household clustering of infection. In contrast, HTLV antibody among Canquintu residents clustered significantly by household. HTLV-associated neurologic disease was not detected in either population. The atypical seroepidemiology observed in both locations might be explained if the virus endemic to the Guaymi differed from HTLV-I previously described in the Caribbean basin and Japan. PMID- 2240370 TI - Persistence of mosquito-borne viruses in Kern County, California, 1983-1988. AB - The persistence of arboviruses was studied from 1983 to 1988 in mixed agriculture, marsh, riparian, and foothill habitats in Kern County, CA. Western equine encephalomyelitis (WEE) virus was isolated frequently during 1983 from Culex tarsalis and Aedes melanimon and was detected by the seroconversion of sentinel chickens. WEE virus then disappeared, even though vector competence studies during 1984-1986 showed that Cx. tarsalis was able to transmit WEE virus. St. Louis encephalitis (SLE) virus was detected sporadically in 3 of the 6 years of the study by isolation from Cx. tarsalis and/or by sentinel chicken seroconversion. When mosquito pools were screened for virus in suckling mice, Turlock (TUR) and Hart Park (HP) viruses were isolated from Cx. tarsalis during each summer. Vertical transmission of HP was indicated by the isolation of virus from a pool of male Cx. tarsalis. California encephalitis (CE) virus was isolated repeatedly from host-seeking Ae. melanimon females, males, and adults reared from field-collected immatures, verifying vertical transmission in nature. Horizontal transmission of CE virus among both jackrabbits (Lepus californicus) and desert cottontails (Sylvilagus auduboni) appeared to amplify Ae. melanimon infection rates during the summer of 1985, but elevated herd immunity depressed infection rates during 1986. Thus, CE, HP, and TUR viruses persisted in Kern County, while WEE virus appeared to become extinct and required reintroduction. The sporadic occurrence of SLE virus activity remains unexplained, but its persistence may require both vertical transmission and reintroduction. PMID- 2240371 TI - Plasmodium falciparum-infected Anopheles stephensi inconsistently transmit malaria to humans. AB - Malaria was transmitted to only 5 of 10 volunteers bitten by 1-2 Anopheles stephensi carrying sporozoites of the 3D7 clone of the NF54 strain of Plasmodium falciparum in their salivary glands. Parasites were detectable by culture in blood taken 7-10 days following exposure and by thick blood film 14-16.5 days after exposure. Infectivity did not correlate with the numbers of sporozoites in the salivary glands. PMID- 2240372 TI - Parasite antigenemia in untreated and treated lymphatic filarial infections. AB - To evaluate the merit of antigen detection assays as a tool to monitor the efficacy of chemotherapy for lymphatic filariasis, we serially measured antigen levels in sera from jirds infected with Brugia malayi and from humans with bancroftian filariasis. Antigenemia was detected in all animals with parasitologically proven infection and was present in jirds with prepatent or occult filariasis. Antigen levels correlated with worm burdens, and progressively declined in drug-cured animals. Treatment with diethylcarbamazine (DEC) triggered a transient increase in serum levels of filarial antigens bearing the epitope recognized by the monoclonal antibody HC 11. All patients with bancroftian filariasis became amicrofilaremic within one week after DEC treatment. Antigenemia levels slowly declined over a period of several months in all but one treated individual. Forty-two months after treatment, progressively rising antigen levels are present in 10 patients. Six of these remain amicrofilaremic; in the other 4, elevated antigenemia levels preceded or were detected at the same time as recurrent parasitemia. Periodic monitoring of antigenemia levels after treatment of patients with lymphatic filariasis can be used to identify individuals who are likely to develop recurrent microfilaremia before the parasites become detectable in blood samples, thereby allowing timely retreatment. PMID- 2240373 TI - Selective breeding of dogs for segregation of limb edema from microfilaremia as clinical manifestations of Brugia infections. AB - Three generations of beagles were monitored for microfilaremia (mf) and clinical disease during repeated infection with Brugia pahangi and were selectively bred for offspring manifesting limb edema and low or amicrofilaremia. A high microfilaremic female mated to a high microfilaremic male produced 7 pups, 6 of which maintained mf greater than 1,000/ml for greater than 2 years after 5 monthly infections of 10 infective larvae each. An uninfected female mated to another high mf male produced 5 pups, 4 of which did not exceed 1,000 mf/ml 7 months after initiation of the repeating infection regimen; 1 of these remained amicrofilaremic after 2 additional challenges. Neither the parents nor the offspring from these matings manifested chronic limb edema. Two matings were conducted with offspring from the microfilaremic female by breeding siblings with the lowest mf and breeding siblings with the highest mf. The high mf siblings produced 4/5 offspring manifesting chronic limb edema (greater than or equal to 7 months duration) and either no mf (in 2 dogs) or less than 100 mf/ml after the repeating infection regimen. The lower mf siblings produced 5 offspring, all with greater than 1,000 mf/ml 6 months after the initiation of the repeating infection regimen; none manifested edema. Comparisons of IgG antibody levels, specific for extracts of adult worms, showed no consistent differences between these 2 litters of dogs that could be associated with limb edema or mf when monitored for 16 months; however, the onset of lymph node enlargement was much earlier in the group of dogs manifesting limb edema than in the other litter. PMID- 2240374 TI - Physical activity, opportunity for reinfection, and sibling history of heart disease as risk factors for Chagas' cardiopathy. AB - A case-control study was conducted to examine whether physical activity, sibling history of heart disease (HHD), and length of residence in an area endemic for Chagas' disease were associated with the risk of developing Chagas' cardiopathy. Two hundred forty-seven cases of Chagas' heart disease and 345 seropositive subjects with normal ECG (controls) were selected in a population survey in Goiania, Brazil. Prevalence ratios for exposure variables were estimated for cases in relation to controls and for subgroups of seropositives with selected ECG abnormalities in relation to controls. Increasing age and male sex were consistently and significantly related to an increased risk of ECG abnormalities. HHD was significantly associated with ECG alterations in 3 of the 5 comparison subgroups (any ECG alteration, right bundle branch block, and left anterior hemiblock). No association was found between length of residence in an area endemic, physical activity, and ECG abnormalities. A sample of 529 seronegative subjects were also examined and the interaction between exposure variables and seropositivity was tested to assess whether the associations found were specific for seropositives. Males were at greater risk of any ECG alteration and left anterior hemiblock in relation to females if they were seropositive. An increasing risk of ventricular premature beats with age was clearer for seropositive than for seronegative subjects. Subjects with HHD were at an increased risk of ECG abnormalities and this was greater in those with a positive serological test (P less than 0.05). The findings suggest a possible geographical clustering or a familial aggregation of cases of Chagas' heart disease. PMID- 2240375 TI - Recurrence rate after discontinuation of long-term mebendazole therapy in alveolar echinococcosis (preliminary results). AB - The recurrence rate was investigated in 19 patients with non-resectable alveolar echinococcosis after discontinuation of a long-term therapy with mebendazole (average treatment 4.3 years). A control group consisted of 14 patients who underwent radical surgery and finished a course of prophylactic postoperative mebendazole treatment of 2 years. In the controls, no recurrence was observed after a post-therapy period averaging 3.5 years. In contrast, recurrence occurred in 7/19 patients (37%) with non-resectable alveolar echinococcosis an average of 1.6 years after discontinuation of the long-term mebendazole therapy. The absence of clinically detectable recurrence in the remaining 12 patients seems to be due either to spontaneous inactivation of alveolar echinococcosis preceding chemotherapy or too short post-therapy surveillance. The patients with recurrence responded favorably to reintroduction of chemotherapy. The data indicate that mebendazole therapy is parasitostatic rather than parasiticidal. PMID- 2240377 TI - The future of general surgery training. PMID- 2240376 TI - Increased abundance, size, and longevity of food-deprived mosquito populations exposed to a fungal larvicide. AB - To determine whether the quantity of food available to mosquitoes in their aquatic environment limits the effectiveness of microbial pathogens as biological control agents, experimentally well-nourished and malnourished larval Aedes aegypti (Linn.) were exposed to graded inocula of the entomopathogenic fungus, Metarhizium anisopliae. First instar larvae were provided access either to 3 or to 5 mg of food, and lots from each food regimen were inoculated with 20, 40, 60, or 80 micrograms of fungal spores/ml water. Application of the fungus to well nourished larvae reduced the proportion developing to the adult stage, and increased the size of those adults that developed; their survival was not affected. In the case of malnourished larvae, such applications appeared not to effect the proportion of larvae that matured, and, paradoxically, increased the size and longevity of these resulting adults. By destroying a portion of the larvae, the pathogen apparently reduced competition among malnourished larvae, thereby enhancing their survival, as well as the size of the resulting adults. Thus, biocontrol agents may fail when used as larvicides against such nutrient deprived mosquitoes as frequently occur in nature. PMID- 2240378 TI - Educational research in perspective. PMID- 2240379 TI - Amputation prevention in an independently reviewed at-risk diabetic population using a comprehensive wound care protocol. AB - An independent review panel composed of an orthopedic surgeon, a vascular surgeon, and an endocrinologist was convened to conduct a case history review. The 71 patients reviewed had 124 wounds on 81 limbs and participated in the comprehensive wound management program of the University of Minnesota. Based on their expertise, the review panel classified the wounds by severity and identified the limb's risk for amputation. The resulting scores were then compared with the patient's actual outcome. The review panel predicted 65 (80%) of the limbs would be salvaged and 16 (20%) would be amputated. The actual outcome was that 75 (93%) of the limbs were salvaged and 6 (7%) were amputated (p less than 0.005). The university's wound management program was highly successful, compared with the predictions of the reviewers. PMID- 2240381 TI - Immediate versus delayed shoulder exercises after axillary lymph node dissection. AB - A total of 144 evaluable patients with breast cancer were enrolled in a multicenter, randomized, prospective study to establish the role of delayed shoulder exercises on wound drainage and shoulder function after axillary lymph node dissection. Patients in group 1 (n = 78) started active shoulder exercises 1 day postoperatively. Patients in group 2 (n = 66) started on the eight postoperative day, following 1 week of immobilization of the arm. Patients in group 2 had 14% less wound drainage volume than those in group 1 (600 +/- 436 mL versus 701 +/- 398 mL); this difference, however, was not significant. Also, no differences could be established between the two groups when duration and volume of wound drainage, number and volume of seroma aspirations, wound complication rates, and shoulder function were compared 6 months after surgery. PMID- 2240380 TI - Algorithm for assessing renal dysfunction risk in critically ill trauma patients receiving aminoglycosides. AB - A recent retrospective study proposed that the following screening criteria be used in identifying critically ill trauma patients receiving aminoglycosides who are at significant risk to develop renal dysfunction: (1) post-admission shock, (2) minimum serum concentration more than 2 mg/L, and (3) diagnosis of septicemia. The major purpose of the present study was to validate these criteria and design a corresponding algorithm for clinical use. All patients admitted to a trauma intensive care unit and receiving an aminoglycosides was also studied. All patients studied over a 7-month period. A control group not receiving aminoglycosides was also studied. All patients were evaluated for the presence of renal dysfunction (i.e., serum creatinine increase greater than or equal to 0.5 mg/dL). Univariate and multivariate statistical analyses were used to compare potential associated risk factors. The overall renal dysfunction incidence was 10% in the treatment patients (n = 93) versus 5% in the control patients (n = 199) (p = 0.13). Sensitivity and specificity of the screening criteria were 67% and 92%, respectively. The predictive values of a positive and negative test relative to correctly labeling patients at high risk or low risk to develop renal dysfunction were 46% and 96%, respectively. Major risk factors associated with renal dysfunction in the treatment group were post-admission shock, minimum serum concentration more than 2 mg/L, and liver dysfunction. Use of three major risk factors has excellent predictive value in identifying severely traumatized patients at low risk for developing renal dysfunction while receiving aminoglycosides. The modest predictive value of a positive test results in conservative management of patients by avoidance of aminoglycosides, i.e., use of alternative antimicrobial agents. PMID- 2240383 TI - Pouch outlet obstruction following vertical ring gastroplasty for morbid obesity. AB - We have experienced a 14% (38 of 264 patients) incidence of pouch outlet obstruction following vertical ring gastroplasty. Initial management consisted of dilatation in 34 of 38 patients (94%). Ten of 34 patients (29%) were spared reoperation by 1 to 3 dilatations. Non-passage of an endoscope through the stoma immediately following dilatation predicted the need for surgery; 4 of 11 patients (36%) with passage underwent reoperation compared with 17 of 20 patients (85%) without passage (p less than 0.02). Surgical findings included "tipped bands" in 9 of 28 patients (32%); fibrous reaction to the band in 10 of 28 patients (36%); adhesions with angulation of the pouch in 2 of 28 patients (7%); and no identifiable cause of obstruction in 7 of 28 patients (25%). Surgical therapy consisted of removal of the band (2 patients), removal of the band and replacement with a similar length or larger band (20 patients), "tacking" the band in the horizontal position (4 patients), or conversion to a Roux-Y bypass (2 patients). The first three options were associated with an unacceptably high rate of weight regain and/or continued symptoms, whereas the last-named procedure met with good success. PMID- 2240382 TI - Fish oil supplementation in patients with stable claudication. AB - Increased blood viscosity occurs in patients with claudication. This increase in viscosity, which is mainly due to elevated fibrinogen levels and a decreased red cell deformability, adversely influences blood flow. In addition to a positive effect on blood pressure, blood lipids, and platelet responsiveness, fish oil may improve blood flow due to a favorable influence on hemorrheology. In a prospective, randomized, double-blind study, we evaluated the effect of six capsules of fish oil (1.8 g eicosapentaenoic acid and 1.2 g docosahexaenoic acid) versus six capsules of corn oil (3 g linoleic acid), administered for 4 months, on walking distances, pressure indices during rest and after exercise, blood pressure, red cell deformability, fibrinogen, and lipid levels in 32 patients with stable claudication. No significant changes in walking distances and pressure indices during rest and after exercise occurred, despite a significant increase in red cell deformability in the fish oil group. Fibrinogen levels did not change in either group. In the fish oil group, a favorable change in blood lipids was noted; high-density cholesterol increased and triglycerides decreased. Mean arterial blood pressure declined to a similar extent in both groups. Thus, short-term supplementation with fish oil does not lead to clinically significant improvement of symptoms in patients with stable claudication. This suggests that red cell deformability is of minor importance in the arterial blood flow in the legs of these patients. PMID- 2240384 TI - An outpatient anticoagulation protocol managed by a vascular nurse-clinician. AB - Lifetime anticoagulation has become a therapeutic option for surgical patients with hypercoagulable states or prosthetic arterial bypass grafts. However, physicians may not achieve optimal anticoagulation or may attempt to limit the length of the therapy period because of the perceived morbidity from hemorrhagic complications of Coumadin therapy. A protocol for anticoagulant therapy monitored and regulated by a vascular nurse-clinician was reviewed. Coumadin was prescribed for 1,891 patient-months to 93 patients to maintain their prothrombin time 1.5 to 2 times control (range: 18 to 24 seconds). The mean (+/- SD) prothrombin time for the study population was 19.8 +/- 1.8 seconds. During follow-up, 472 (14%) of 3,479 prothrombin times measured were below the therapeutic range (n = 232) or prolonged (n = 240), prompting an adjustment in the Coumadin dose in 82 (88%) patients. Four patients developed recurrent vascular graft thrombosis while receiving anticoagulation. There were 6 major and 11 minor hemorrhagic complications. Patients with a chronic risk for arterial or venous thrombosis can have out-patient anticoagulant therapy administered at optimal intensity and regulated safely with a low incidence of hemorrhagic and thrombotic events. PMID- 2240385 TI - Comparison of blood flow assessment between laser Doppler velocimetry and the hydrogen gas clearance method in ischemic intestine in dogs. AB - Blood flow of the colon and the ileum was measured before and after intestinal devascularization by laser Doppler velocimetry and the hydrogen gas clearance technique in 10 dogs in order to evaluate the clinical usefulness of laser Doppler velocimetry. The submucosal blood flow of the colon and the ileum measured by the hydrogen gas clearance method was significantly decreased, as was the subserosal blood flow of both sites measured by laser Doppler velocimetry. There was a linear relationship between the flow values using the two methods both in the colon (r = 0.7192, p less than 0.001) and in the ileum (r = 0.7646, p less than 0.001). These data suggested laser Doppler velocimetry may be a useful method to assess the degree of intestinal ischemia because of its noninvasiveness and good correlation with submucosal blood flow by the hydrogen gas clearance technique. PMID- 2240386 TI - Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion. AB - Massive transfusion may cause abnormalities of electrolytes, clotting factors, pH, and temperature and may occur in a scenario of refractory coagulopathy and irreversible shock. Identification of correctable variables to improve survival is complicated by the interplay of this pathophysiology. Temperature may be an under-appreciated problem in the genesis of coagulopathy. In vitro studies have demonstrated that platelet function and vascular response are critically temperature-dependent. We reviewed the records of 45 trauma patients without head injury or co-morbid medical illness who required massive transfusions. The mean Injury Severity Score was 55 +/- 6, a mean of 22.5 +/- 5 units of blood was transfused, and mortality was 33%. Nonsurvivors were more likely to have had penetrating injury (88% versus 55%), received more transfusions (26.5 +/- 9 versus 18.6 +/- 1, p less than 0.05), had lower pH (pH 7.04 +/- 0.06 versus 7.18 +/- 0.02, p less than 0.05), had lower core temperature (31 +/- 1 degree C versus 34 +/- 1 degree C, p less than 0.01), and had a higher incidence of clinical coagulopathy (73% versus 23%). Severe hypothermia (temperature less than 34 degrees C) occurred in 80% of the nonsurvivors and in 36% of survivors. Patients who were hypothermic and acidotic developed clinically significant bleeding despite adequate blood, plasma, and platelet replacement. Avoidance or correction of hypothermia may be critical in preventing or correcting coagulopathy in the patient receiving massive transfusion. PMID- 2240387 TI - Relationship of oxygen dose to angiogenesis induction in irradiated tissue. AB - This study was accomplished in an irradiated rabbit model to assess the angiogenic properties of normobaric oxygen and hyperbaric oxygen as compared with air-breathing controls. Results indicated that normobaric oxygen had no angiogenic properties above normal revascularization of irradiated tissue than did air-breathing controls (p = 0.89). Hyperbaric oxygen demonstrated an eight- to ninefold increased vascular density over both normobaric oxygen and air breathing controls (p = 0.001). Irradiated tissue develops a hypovascular hypocellular-hypoxic tissue that does not revascularize spontaneously. Results failed to demonstrate an angiogenic effect of normobaric oxygen. It is suggested that oxygen in this sense is a drug requiring hyperbaric pressures to generate therapeutic effects on chronically hypovascular irradiated tissue. PMID- 2240388 TI - Variations in sensitivity after sectioning the intercostobrachial nerve. AB - The authors present a prospective study of the variations in sensitivity that appear in the armpit and arm after the intercostobrachial nerve has been sectioned in a modified radical mastectomy. Of a total of 208 patients studied between 1978 and 1987, the intercostobrachial nerve was sectioned in 139 patients, whereas in 30 it remained intact; in 39 patients only peripheral branches of the nerve were sectioned. The patients were examined at regular postoperative intervals in order to evaluate their sensitivity both to touch and to pain in the axilla and arm. Four hundred thirty-three examinations were carried out and the 3 operative groups were assessed accordingly. After the nerve was sectioned, there was increasing anesthesia in the armpit and hypoesthesia on the posterointernal face of the arm, while for the patients in whom the intercostobrachial nerve remained intact, these alterations were less intense and long-lasting. Significant statistical differences between the two groups also exist. In the absence of axillary lymphatic ganglia infiltrated by the tumor, the conservation of the intercostobrachial nerve is recommended. PMID- 2240389 TI - Surgical management of the redundant transposed colon. AB - Redundancy of the transposed thoracic colon is not uncommon. Rarely, however, when accompanied by severe symptoms, it may necessitate surgical correction. We describe herein a surgical technique that allows the stretching and straightening of the redundant transposed organ. PMID- 2240390 TI - Rectal prolapse in infants and children. AB - Rectal prolapse that is intractable to the usual medical therapy was successfully managed without significant complications in 10 patients by simple subcutaneous encirclement of the anus with a heavy nonabsorbable suture, which was in place until the suture was removed or broke after 4 to 6 months. Four patients required two sutures and one needed a third insertion. Since this procedure is simple, has no serious complications, and controls rectal prolapse, it is recommended as the preferred initial surgical treatment of this condition. PMID- 2240391 TI - Prevention of pancreatic fistula by modified pancreaticojejunal anastomosis. AB - A major cause of morbidity after pancreatoduodenectomy is leakage from the pancreaticojejunal anastomosis. To prevent this complication, we have employed mucosal stripping from the proximal jejunum prior to end-to-end anastomosis in 19 patients with good results. PMID- 2240392 TI - Role of surgery in antibiotic-induced pseudomembranous enterocolitis. AB - With the increased use of prophylactic and broad-spectrum antibiotics, pseudomembranous colitis has emerged as a significant clinical problem. Management with specific anti-Clostridium difficile therapy (vancomycin or metronidazole) has reduced mortality to less than 2%. Nevertheless, the disease may progress to a fulminant toxic colitis or colonic perforation. Additionally, another subset of patients will present with a dramatic clinical picture, suggesting acute peritonitis, eventuating in unnecessary laparotomy. This report reviews both the medical and surgical literature during the past 15 years of patients treated for pseudomembranous colitis. Analysis of this clinical data has provided us with the opportunity to both define the role of surgery in this disorder and illustrate the necessity for a combined medical and surgical cooperative approach in the early management of this iatrogenic disease. PMID- 2240393 TI - Acute pancreatitis after experimental pancreatic transplantation. PMID- 2240394 TI - Various materials used for hernia repair. PMID- 2240395 TI - [Anesthesia of wild animals using hypodermic devices]. AB - Narcosis of wild animals, using projectile arms has modified and simplified considerably the restraint it was inevitably made under stress conditions for the animals before. The sedative drugs used have an analgesic effect which give us the opportunity to be able to practise some surgeries directly in the outside or inside enclosure of the animals. In the meantime, animal approach should be done carefully and the behavior of the zoologist before and after the shooting is the main key of success. PMID- 2240397 TI - [Communication networks in great natural disasters]. AB - A great natural disaster destroys every energy supplies and the communication network necessary for the organisation of health care (telephone, telex) is entirely or partially not functioning. It becomes impossible to be informed about the hospitals and others sanitary availabilities in the disaster area. Our personal experience, during the El Asnam's and Mexico's earthquakes demonstrates the necessity to maintain a functioning network for sanitary use. The unique possibility is the availability of portable, battery operated radio-transmitters. It is necessary to have these equipment in all hospitals and health centers in the area of a previsible disaster. A good scheduled training is necessary for the medical and paramedical personal of these areas. PMID- 2240396 TI - [Particularities of the anesthesia of domestic carnivora]. PMID- 2240398 TI - [Value of the 2000 radiocom system for a SAMU in a rural area]. AB - The department "Meuse" is a region with a low density of population (190,000 inhabitants). The creation of a "SAMU" is quite recent (February 1988). The financial means allowed were limited so they didn't enable us to develop a radio netword peculiar to the "SAMU". The arguments which made us adopt the use of the 2000 Radiocom as a basic means of communication for "SAMU 55" are: immediate creation; reduced installation cost; preservation of the medical secret and possibility of extension. PMID- 2240399 TI - [Value of the radionetwork of the transportation company in Besancon for alarm forwarding]. AB - The C.B. users offered for a few years a way for putting-out the distress on the highway. There were 2,000 in Besancon and surroundings in 1982. Today they are becoming no existent. Since then a new system of alarm run is born with 150 buses, 178 kilometers of net-travel and a sweep frequency of 10 min from 6h30 a.m., to 8h p.m, and of 30 min until 12h p.m. The 250 "C.T.B." drivers assume a regular surveillance of the urban and suburban highways. A standard message in used between the C.T.B. (Besancon Company of Buses.) regulation and Samu 25, regulation which allows to fix circumstances, place of road accident and inventory of casualties: 27 emergency calls are received in 1987, 50 in 1988. It might be possible to use other private or public radiotelephonic network. PMID- 2240400 TI - [10 fatal endocarditis: autopsy observations, causes of death]. AB - Among 841 autopsies realized between january 1982 and september 1988, by the Pathological the department of Amiens University Hospital the ten patients dead of infectious endocarditis have been autopsied. Macroscopic and microscopic observations have two cases of acute endocarditis and eight of subacute endocarditis. For the two patients dead of acute endocarditis, autopsy affirms the cardiovascular etiology of death. For the eight cases of subacute endocarditis, necropsic findings differs from the germs. In the three cases where the germ is a Staphylococcus aureus, the diagnosis of endocarditis was made before death and the cardiovascular etiology of death was affirmed by autopsy. For the other germs (3 Streptococcus sp, 1 Salmonella typhimurium, and 1 germ unknown), the diagnosis of endocarditis was made by autopsy, but necropsy disclosed the cause of death in only two cases. PMID- 2240401 TI - [Accidental hypothermia in adults: taking charge by the SAMU of Paris]. AB - Thirty one cases of accidental hypothermia have been taken in care by the SAMU de Paris during the year of 1987. The accidental hypothermias happening in the cities are, most of the time, moderated and not very serious. The search for a cause is a prime necessity. The prognosis is based on that search to guide and advise the patients. PMID- 2240402 TI - [Current practice of drug trials in healthy volunteers]. AB - It is impossible to extrapolate for men the animal's data. Pre-therapeutical studies are a necessity to state precisely in man ADME for a new drug and to confirm pharmacological properties seen in animals. Very often, the only healthy volunteers are useful for Phase 1 studies: The selection of volunteers keeps physical and metabolic status, and psychological motivation. True but restricted information is necessary for "free and informed consent". Rights and duties must be clearly defined in written convention. Financial advantages are in agreement of trouble but not of hazard in the study. The safety is the main point in human studies. That means a safe methodology and a protocol approved by independent ethical committee. The monitoring of these studies must be precisely conducted with many clinical and laboratory examinations. Healthy volunteers studies are required by French Ministry of Health, rejected by medical law, condemned by civil law but covered by legal insurances. In French mind is illicit that is not specifically permitted by law. We need special legislation as we refuse medical and ethical responsibility. PMID- 2240403 TI - [Repetitive inhalation anesthesia in rats]. AB - Inhalational anesthesia in the rat seems a good process, by a rapid induction and awakening if a steady state ventilation-perfusion ratio and no pollution are obtained. Animals are cooped up in an "induction-box" which is joined to a scavenger system. Anesthesia maintenance is assumed with a Bain circuit and allows short and frequent anesthesia. Isoflurane does not markedly decrease circulatory and respiratory factors at low concentration (2%). So any anaesthetist can do himself such a practical system. PMID- 2240404 TI - [Flumazenil and volatile anesthetics. Study of possible interferences in rats]. AB - Many works suggest contradictory experimental or clinical results of flumazenil effects during inhalation anaesthesia. In ten rats anaesthesia was induced with 5% isoflurane or halothane during one minute and maintained during 5 minutes with 1% the same halogene anaesthetic in 50% N2O and O2. Then 0.2 mg of flumazenil or a same volume of placebo were administered intraperitoneally and during the last 5 minutes, the rats were exposed in 1% volatile anesthetic gas flow. Sleep times were measured in terms of reestablishment of the righting reflex. Each rat was anesthetized four time: halothane and isoflurane, with flumazenil or placebo. In those conditions, there were no significant changes in sleep times either the anaesthesia were associated, with flumazenil or with placebo. PMID- 2240405 TI - [Prevention of venous thrombosis in neurosurgery]. AB - Prophylaxis of thromboembolism in the neurosurgical patient remains a difficult problem as anticoagulant treatment increases the inherent risk of hemorrhage into the operative site. This review report the incidence of lower extremity deep vein thrombosis given in the literature, and the results of an european investigation realised during september 1988. PMID- 2240406 TI - [Epidemiology and etiopathogenesis of deep venous thrombosis of the lower limbs]. AB - Deep venous thrombosis and pulmonary embolism are frequent complications of surgery. A careful evaluation of both the thromboembolic and the haemorrhagic risks depends on the type of intervention and associated individual risk factors. Such an evaluation should allow allocating the patient to an appropriate prevention which consists of mechanical and/or pharmacological means. PMID- 2240407 TI - [Hip arthroplasty and thromboembolic complications]. AB - Orthopedic department of Centre hospitalo-universitaire de Brest use one upon another two procedures: from 1974 to 1984, for 1287 cases the prevention of thromboembolic complications is done with the help of subcutaneous heparin at standard dose during 12 days; the clinical diagnosis in confirmed by an isotopic phlebography and isotopic lung scan. In 1986 and 1987, for 391 cases this prevention is done with the help of subcutaneous heparin in adapted doses during 21 days; the clinical diagnosis is confirmed by X ray phlebography and isotopic lung scan. The frequency of thromboembolic complications has been 4.6% in the first period and 1.2% in the second period. This results confirm the role of heparin in preventing post operative thromboembolic complications after total hip replacement. The results after knee arthroplasty are not so good. PMID- 2240408 TI - [Spinal anesthesia and prevention of thrombosis by heparin]. AB - Non traumatic spinal hematomas are a rare pathology, anticoagulant treatments are one of their most frequent etiology. Therefore, the association of spinal anesthesia and a preventive treatment which has antithrombotic aim by the use of subcutaneous heparin (non fragmented or low molecular weight) is being discussed by many authors. It is lawful to associate spinal anesthesia with a soft dose of non fragmented subcutaneous heparin (Kakkar method) if the protocols are strictly respected. It is certainly possible to use low molecular weight subcutaneous heparin as well. However a slight decline in their use urges anyone to be very cautious. PMID- 2240409 TI - Pathology of peripheral vestibular disorders in the elderly. AB - A clinical classification of vertigo commonly seen in the elderly and caused by peripheral vestibular disorders is illustrated by case reports and temporal bone histopathology. The classification includes inducible transient vertigo and noninducible protracted vertigo. The peripheral vestibular pathology includes abnormalities of sensory, neural, and mechanical structures and is often asymmetric. The pathogenesis of these disorders is often speculative, but includes degenerative, infectious, neoplastic, and vascular insults to the vestibular labyrinth. PMID- 2240410 TI - Schwann cells associated with vestibular ganglion cells in the aging rat. AB - The purpose of this study was to quantify any age-related change in the components of Schwann cells associated with vestibular ganglion cells: adperikaryonal Schwann cell cytoplasm, myelin bubbles, compact myelin, Schwann cell lipofuscin, or mitochondria in addition to extracellular intraganglionic space. Studies were carried out in young (Y, 3 to 5 months of age, N = 6), old (0, 24 to 26 months of age, N = 3), and very old (VO, 28 to 31 months of age, N = 6) female Wistar rats using point counting stereologic techniques. Recent reports have demonstrated age-related increases in the peripheral nerve counterparts to the following entities: adaxonal Schwann cell cytoplasm, myelin bubble, endoneurial space, and a decrease in Schwann cell mitochondria. Our results indicate no age-related change in the volume fraction of extracellular intraganglionic space (Y, 0.179 +/- 0.04; O, 0.174 +/- 0.049; VO, 0.205 +/- 0.043), adperikaryonal Schwann cell cytoplasm (Y, 0.026 +/- 0.008; O, 0.019 +/- 0.003; VO; 0.028 +/- 0.007), myelin bubble (Y, 0.004 +/- 0.003; O, 0.011 +/- 0.009; VO, 0.006 +/- 0.002), Schwann cell lipofuscin (Y, 0.002 +/- 0.001; O, 0.004 +/- 0.003; VO, 0.002 +/- 0.001), or mitochondria (Y, 0.194 +/- 0.019; O, 0.208 +/- 0.024; VO, 0.205 +/- 0.04). The only age-related change was an increase in compact myelin (Y, 0.006 +/- 0.001; O, 0.008 +/- 0.006; VO, 0.011 +/- 0.004). These findings differ from those of the peripheral nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240411 TI - Distortion product otoacoustic emissions in normal and hearing-impaired ears. AB - Otoacoustic emissions of distortion products (DPOAE's) were recorded in normal and hearing-impaired human ears using relatively straightforward methods. Two pure-tone stimuli at fixed frequency levels of 73 dB HL for f1 and of 67 dB HL for f2 were used. The frequencies of the two primaries were chosen so that their geometric mean represented standard audiometric frequencies. Measurements of the emission amplitudes at 2f1-f2 and the adjacent noise floor were achieved by spectral averaging. A total of 101 subjects (199 ears) were tested. Seventy-seven ears in 46 subjects had normal hearing (hearing levels less than or equal to 20 dB at standard audiometric frequencies; average hearing levels, less than or equal to 10 dB). Thirty-six ears in 25 subjects had near-normal hearing (no hearing complaints, hearing levels less than or equal to 40 dB; average hearing levels, less than or equal to 20 dB). No significant differences in mean DPOAE values were apparent between these two groups of ears. All but two of these 113 ears (98%) showed emissions at three or more of the six frequencies tested between 1 and 6 kHz. Emissions were detected in more than 75% at each frequency between 1 and 6 kHz and in more than 85% between 1 and 4 kHz. A further 86 ears in 44 subjects exhibited varying degrees of sensorineural hearing loss caused by different pathologies. In general, emission amplitudes approximated the shapes of the audiograms, and a highly significant correlation between hearing thresholds and emission amplitudes was demonstrated in the frequency range of 1 to 4 kHz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240412 TI - Osteoradionecrosis of the mandible: pathogenesis. AB - Although the precise pathogenic mechanisms are not fully understood, osteoradionecrosis of the mandible is caused by radiation-induced cellular injury, ultimately resulting in a chronic, nonhealing wound. This etiology does not explain the strong predisposition of the mandible to radionecrosis relative to the maxilla, and overlooks the contribution of ischemic necrosis due to radiation-induced disturbances in circulation. In this study, irradiated mandibles with and without osteoradionecrosis and nonirradiated mandibles were examined histologically. Our findings show that osteoradionecrosis of the mandible is an ischemic necrosis due to radiation-induced obliteration of the inferior alveolar artery, while revascularization by branches of the facial artery is disturbed by radiation-induced vascular disease and periosteal damage. The most vulnerable part of the mandible is the buccal cortex of the premolar, molar, and retromolar regions. PMID- 2240413 TI - Effect of electrical stimulation on middle latency response in the guinea pig. AB - A temporary threshold shift (TTS) has been demonstrated in the electrically evoked middle latency response (EMLR) following exposure to moderate levels of continuous electrical stimulation via a cochlear implant. The threshold at which the EMLR was elicited in chronically implanted guinea pigs was elevated by approximately 100% following 30 minutes of moderate intensity (200 microA or more) sinusoidal electrical stimulation of the cochlea. Results obtained under anesthesia varied unacceptably. In awake animals, EMLR thresholds were stable over time and consistent TTSs were observed. The threshold returned to prestimulation levels within 4 hours following termination of the stimulation. The possibility of histopathologic changes and the relevance of these findings in setting safe output levels for cochlear implant processors are discussed. PMID- 2240414 TI - Pharyngoesophageal intubation injuries: three case reports. AB - The hypopharynx and cervical esophagus are particularly vulnerable to intubation trauma. Contributing factors include hasty intubation by inexperienced personnel; the use of curved, beveled endotracheal tubes containing stylets; malpositioning of the head, and the application of cricoid pressure. Iatrogenic pharyngoesophageal perforations may go unsuspected until characteristic signs and symptoms are recognized. These include cervical pain, fever, dysphagia, leukocytosis, subcutaneous emphysema, and pneumomediastinum. We present three cases that illustrate important points in recognizing, evaluating, and treating pharyngoesophageal perforations. The third case presents a chronic cervical esophageal perforation with secondary pseudodiverticulum, requiring resection of the pseudodiverticulum and a primary sternocleidomastoid muscle flap repair of the cervical esophageal defect. To our knowledge, this technique has not previously been reported. PMID- 2240415 TI - Tumors of diverse histology are sensitive to rhodamine 123 laser phototherapy in vitro. AB - Rhodamine 123 has been shown to be an efficient photosensitizer for the argon laser treatment of a human squamous carcinoma and a melanoma cell line in vitro. Rhodamine 123 laser phototherapy also eradicates these human squamous cell carcinomas when grown as subcutaneous tumor transplants in athymic mice. This study extends these observations by testing a panel of 19 human tumor cell lines of various histologic origins for in vitro sensitivity to rhodamine 123 and the argon laser. Rhodamine 123 with an absorption maxima of 502 nm in water was found to undergo a redshift to 516 nm after uptake by the mitochondria of human tumor cells. Rhodamine 123-sensitized brain tumor cells were inhibited by over 80% after 15 seconds and by 98% after 60 seconds of laser exposure (514.5 nm, 4 W, Tmax = 39 degrees C), as measured by reduced [3H]thymidine incorporation into cellular DNA. Laser or rhodamine 123 alone did not significantly inhibit (greater than 20%) tumor cell [3H]thymidine uptake. Sensitization with 20 micrograms rhodamine 123 for 1 hour before 45 seconds of laser illumination decreased cell [3H]thymidine uptake by 40% to 99% in four melanoma lines, five carcinomas, five leukemias, and four of five other human tumor lines. Two melanomas, two leukemias, and a lymphoma cell line also exhibited a 70% to 80% reduction in [3H]thymidine uptake after sensitization in vitro with 1 microgram/mL rhodamine 123 and laser illumination. Rhodamine 123-sensitized tumor cells were inhibited even more strongly by fractional dose laser irradiation at nonthermal temperatures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240417 TI - Clinical radiology quiz. Case no. 7. PMID- 2240416 TI - Parathyroid carcinoma: clinical presentation and treatment. AB - Parathyroid tumors account for only a small percentage of all head and neck neoplasms. The overwhelming majority of these are parathyroid adenomas that result in primary hyperparathyroidism. From 0.5% to 4% of hyperparathyroid patients, however, will be found to have a parathyroid carcinoma. In this paper, the authors relate their recent experience with such a patient and with two other such cases. Parathyroid carcinoma patients usually present with striking hyperparathyroidism and hypercalcemia, with the resultant related symptoms being more severe than those associated with parathyroid adenomas. Parathyroid carcinomas also tend to be large and may be detectable by current imaging techniques. The surgical appearance of these lesions is also distinct; the tumors are frequently multilobulated, gray-tan in color, quite firm, and often invasive. These physical findings are important since frozen section diagnosis may be difficult. The final histologic diagnosis depends on the presence of mitotic figures and capsular and vascular invasions. Preoperative medical problems, surgical approach, and prognostic factors are also discussed. PMID- 2240418 TI - The intensive psychoanalytic psychotherapy of a severe narcissistic personality disorder in adolescence. PMID- 2240419 TI - The family in treatment during the long-term inpatient care of the adolescent. PMID- 2240420 TI - The American educational system and the psychological development of the adolescent. PMID- 2240421 TI - Running away from treatment: observations and admission predictors for hospitalized adolescents. PMID- 2240422 TI - Reflections on the hospital treatment of adolescents at Chestnut Lodge. PMID- 2240423 TI - Developmental issues in young adulthood: psychoanalytic perspectives. PMID- 2240424 TI - The cohesive self, the nuclear self, and development in late adolescence. PMID- 2240425 TI - In defense of parents. PMID- 2240426 TI - Object relations in borderline adolescents and adults: developmental differences. PMID- 2240427 TI - Developmental anxieties in adolescence. PMID- 2240428 TI - Consistency and change in personality characteristics and affect from middle to late adolescence. PMID- 2240429 TI - Violence and unrestrained behavior in adolescents. PMID- 2240430 TI - Panic disorder in children and adolescents: a review with examples. PMID- 2240431 TI - Who mothers young mothers? Treatment of adolescent mothers and their children with impaired attachments. PMID- 2240432 TI - Adolescents in residential treatment: a six-year comparison. PMID- 2240433 TI - Non-self-controlled adolescents: applications of cognitive-behavioral therapy. PMID- 2240434 TI - Revenge or tragedy: do nerds suffer from a mild pervasive developmental disorder? PMID- 2240436 TI - The evolution of two-tiered health care. PMID- 2240437 TI - The termination of treatment in adolescents. PMID- 2240438 TI - The long-term setting. PMID- 2240435 TI - The first few minutes: the engagement of the difficult adolescent. PMID- 2240439 TI - [Informative value of Doppler ultrasonography in predicting the development of gestoses and fetal growth retardation syndrome]. AB - Doppler studies in 102 women with uncomplicated pregnancies have indicated that uteroplacental and fetoplacental circulations as low-resistant vascular systems develop at 13-16 week's gestation. Doppler examination early in the second trimester allows one to identify hemodynamic disorders in the materno-placental fetal unit and predict their onset as well as toxemia of pregnancy and intrauterine growth retardation. PMID- 2240440 TI - [Use of hyperbaric oxygenation in the prevention of functional uterine disorders in pregnant women with gestoses]. AB - Rheography revealed abnormalities of uterine hemodynamics in 71 women with toxemia of pregnancy. Three-five hyperbaric oxygenation treatments as part of the management were found to be associated with a significant improvement of its efficacy and normalization of hemodynamic status. Longer regimens of hyperbaric oxygenation resulted in a persistent increase in peripheral vascular resistance. PMID- 2240441 TI - [Organization of intensive therapy of eclampsia and eclamptic coma]. AB - This is an overview of counselling, medical and methodological assistance given to obstetric facilities of the Moscow region during 10 years. It is concluded that regional obstetric-gynecologic centers should be established, which incorporate an intensive care unit and a mobile resuscitation team. PMID- 2240442 TI - [Use of helium-neon laser irradiation in prenatal prevention of uterine inertia]. AB - This paper reports results of clinical and experimental studies which sought to validate endonasal laser treatment for prevention of dysfunctional labor in late toxemia. Electrophysiologic and histochemical studies showed stimulating effects of the helium-neon laser treatment on function of large cell hypothalamic nuclei and uterine contractility. Clinical efficiency of this treatment was seen as a lower incidence of dysfunctional labor and cesarean section. PMID- 2240443 TI - [Weight gain during pregnancy in relation to somatic types of women]. AB - The paper presents findings on weekly weight gain in pregnant women as related to constitutional make-ups. Normal and apparently normal pregnant women who were followed up at an antenatal clinic from 7-8 to 40-41 week's gestation have been assigned at the beginning of pregnancy to three weight groups: normal body weight, excessive body weight due to increased fat deposition and deficient body weight. Anthropometric measurements at 7-8, 25-26 and 36-37 weeks showed that weight gain and fat accretion were highest in pregnancies with an initial deficient body weight and lowest in pregnant women with adiposity. Correlation analysis suggested that there was a relationship between the maternal body weight, gestational weight gain and neonatal birthweights. Since women with initial deficient body weights have a wider range of weight gain, as compared with other somatic types, dietary restriction counselling should be cautious and adequate. PMID- 2240444 TI - [Prognostic value of the data of ultrasonographic diagnosis of uterine hemorrhage during pregnancy in patients with threatened abortion]. AB - Ultrasonographic follow-up of 240 pregnant women with congenital and acquired uterine malformations in 135 (56.3%) of them has detected bleedings at various gestational dates. Ultrasonographic correlates of bleedings were ascertained. Bleedings proved to be a significant determinant of outcome. Profuse transient bleedings were associated with a 2-3-fold higher risk of spontaneous abortion and premature delivery while longer and scarce bleedings correlated with a higher incidence of ++non-progressing pregnancy. A low placenta insertion was found in 50-65% of the patients. This evidence indicates a need for early identification of pregnancies with low placenta insertion in order to prevent bleedings. Ultrasonography is essential for appropriate hemostatic and corrective therapy. PMID- 2240445 TI - [Use of UV-irradiated autologous blood in obstetrics and gynecology]. PMID- 2240446 TI - [Differential prevention of recurrence of thrombosis during pregnancy]. AB - Pregnancy in patients with a history of thrombotic complications puts them at a great risk of thrombosis and obstetric complications (hypoxia, intrauterine hypotrophy, bleedings). Functional strain of the hemostasis system occurs at the onset of pregnancy in women with a history of thrombotic complications without clinical symptoms of thrombosis. The incidence of disseminated intravascular coagulation with activation of both pro-coagulation and platelet-mediated hemostasis is 33% and that with activation of only platelet-mediated hemostasis is 64%. Differential use of antithrombotic drugs prevents thrombosis recurrence in 98% of patients. PMID- 2240447 TI - [Effect of maternal genotype characteristics on fetal adaptation to intra- and extrauterine conditions]. AB - Effects of the maternal genotype on the fetal and neonatal compensatory-adaptive patterns have been examined in 1396 newborns. Correlations were found between the ante- and intrapartum progress, physical development of the newborns, early neonatal course and the maternal phenotype. Maternal-fetal compatibility was found to influence the neonatal status and later morbidity and mortality. The maternal phenotype should be considered in the evaluation of risks during the development of medical and preventive activities. PMID- 2240448 TI - [Recording of fetal respiratory movements based on studying the shifting of the amniotic fluid in the trachea by the Doppler effect]. AB - Examination of 80 women in their third trimester with chronic fetal abnormalities has shown that movement of the amniotic fluid in the fetal trachea can be detected during fetal respirations. The pattern of amniotic fluid velocity is significantly affected by chronic fetal stress. Evaluation of pneumodopplerographic findings enables identification of 90% of satisfactory and 80% of poor fetal conditions. PMID- 2240449 TI - [Ectopic pregnancy after the treatment of infertility by the method of extracorporeal fertilization]. AB - During October 1987 to June 1989, 609 infertile couples have been treated using in vitro fertilization and embryo transfer (IVF-ET). Of 78 conceptions (15.7% of transferred embryos), 6 (7.7%) pregnancies were ectopic (5 tubal and 1 ovarian). After diagnosis of ectopic pregnancy all the patients were operated; the ovary was resected in 1 patients and tubectomies were done in 5 patients (laparoscopically in 1). All the diagnoses were confirmed histologically. Since prevention of ectopic pregnancy in IVF-ET is not reliable, the patients enrolled for IVF-ET should be considered to be at risk and closely followed up. PMID- 2240450 TI - [Transvaginal ultrasonography in the treatment of infertility by the method of extracorporeal fertilization]. AB - Menstrual cycles of 274 women have been analyzed in order to decide on possibility of follow-up of follicular growth and development using echography and retrieval of preovulatory oocytes using sonographically guided transvaginal access during in vitro fertilization and embryo transfer (IVF-ET). Transvaginal echography proved to be a very efficient tool in monitoring follicle growth during an IVF-ET program and outpatient oocyte retrieval with a minimal injury. PMID- 2240451 TI - [The course of hypoplastic anemia in women with uterine hemorrhage]. AB - The clinical course of hypoplastic anemia (HA) has been assessed in 21 patients with uterine bleedings. The disease was associated with severe onset and progress, profound pancytopenia and myelodepression or even critical states. Superimposed infectious inflammatory and other diseases aggravated HA by promoting hemorrhagic events, especially uterine bleedings. An initial treatment using packed erythrocyte transfusions and glucocorticoid hormones reversed anemia and hemorrhages in 11 of 21 patients with HA. Splenectomy was performed in 8 and ovariectomy in 1 of 11 patients whose blood and bone marrow tests improved after the treatment. The other 12 patients were maintained on transfusion and drug regimens. The efficacy of splenectomy and other interventions for HA in women with uterine bleedings depends on an response to received treatments. PMID- 2240453 TI - [Changes in serum sialic acid levels in patients with ovarian tumors in the process of treatment]. PMID- 2240452 TI - [Pathogenesis of damaging effects of hyperoxia during early ontogenesis]. PMID- 2240454 TI - [Interpretation of morphological changes in the tissues and organs of the reproductive system after radical surgical treatment of uterine leiomyoma]. AB - Ovarian and endometrial changes in most patients with uterine myoma had a histophysiologic nature. Clinical symptoms of "rapid growth" of myoma were largely determined by degenerative changes in the tumor and the surrounding myometrium. Uterine bleedings in patients with myoma may be related to hyperplastic lesions of the ovaries and endometrium, vascular myometrial and hemodynamic endometrial disorders. PMID- 2240456 TI - [Fetal craniopharyngioma (ultrasonographic and pathological studies)]. PMID- 2240455 TI - [The role of metabolic changes in the pathogenesis of bronchial asthma in pregnancy]. PMID- 2240457 TI - Somatosensory evoked potentials and adaptation to extrauterine life: a longitudinal study. AB - In order to compare longitudinal data with existing cross sectional extrauterine life data on somatosensory evoked potentials (SEPs), two groups of appropriate for gestational age optimal premature infants were studied. Group A consisted of 8 infants born between 34 and 36 weeks gestational age (GA). In this group, SEPs were recorded within 24 hours after delivery and then every 48-72 hours until discharge. Group B consisted of 7 infants born between 29 and 33 weeks GA. In these infants, SEPs were recorded at weekly intervals from the second week onwards. In group A, a marked decreased in the N1 latency was seen during the first week of life. Six infants had initial values above the normal range. During the second week of life this decrease paralleled the cross sectional data. In group B all the infants had a N1 latency within the normal range and the longitudinal data paralleled the cross sectional data. These findings must be taken into consideration when SEPs are used to assess the neurological integrity of the newborn during the first week of life. PMID- 2240458 TI - Studies on pediatric patients with absent auditory brainstem response (ABR) later components. AB - Eleven pediatric patients with only wave I or waves I and II of their ABR were clinically analyzed. The clinical diagnoses of these patients were as follows: 1) anoxic encephalopathy in two cases; 2) neonatal asphyxia in one; 3) infantile Gaucher's disease in one; 4) mitochondrial encephalomyopathy in one; 5) suspected Pelizaeus-Merzbacher disease in three; 6) degenerative disease of unknown etiology in two (presumptive diagnosis were progressive supranuclear palsy and dentate-rubro-pallido-Luysian atrophy); and 7) infantile spasms with congenital malformation of the brain and bones in one. The incidence of the patients with this type of ABR abnormality was 0.67% among 1,650 of our pediatric patients whose ABRs were examined because of audiological or neurological problems. All eleven patients showed severe mental retardation. Nine of the eleven had convulsions and likewise, eight of eleven showed deterioration in mental and/or motor activities. Furthermore seven of eleven had disturbed consciousness and four of these seven were in deep coma. Other brainstem and bulbar signs and symptoms were frequently found in these patients. In our series, patients without the later components of ABR manifested marked neurological abnormalities inside and outside the brainstem. PMID- 2240459 TI - Glucose, free fatty acid and ketone body metabolism in Duchenne muscular dystrophy. AB - We examined how the substances, especially glucose, free fatty acids (FFA) and ketone bodies, and hormones associated with energy metabolism change with the disease progress in Duchenne muscular dystrophy (DMD). Serum creatine kinase (CK) activity was used as an index of the stage of DMD, because this activity is exponentially decreases with the progress of the disease. The glucose concentration in DMD patients with CK activity of less than 1,000 U/l (low CK) was significantly lower than that in controls, although there was no significant difference between that in DMD patients with CK activity of more than 1,00 U/l (high CK) and that in controls. The FFA concentration in both high CK and low CK patients was significantly higher than that in controls. The FFA concentration in low CK patients tended to be higher than that in high CK patients. The ketone body concentration in low CK patients was significantly higher than that in controls and that in high CK patients. The [glucagon]:[insulin] ratio in low CK patients was significantly higher than that in controls and that in high CK patients. It was also observed in a correlational study that the glucose concentration decreased with the age and the decrease in CK activity, i.e., with the progress of DMD. The FFA and ketone body concentrations increased with the decrease in the glucose concentration. The decrease in the glucose concentration may be due to a caloric shortage and/or degenerated muscle, which cannot supply enough gluconeogenic substrates, such as alanine. The kinetics of insulin and glucagon in DMD may help to maintain the glucose metabolism. Increased concentrations of FFA and ketone bodies may be helpful in the advanced stage of DMD, as energy sources and as substrates, sparing muscle protein. PMID- 2240460 TI - Mucolipidosis III and Bardet-Biedl syndrome in the same family: diagnostic pitfalls. AB - Two brothers, offspring of an Arab inbred family suffered from both mucolipidosis III (ML-III) and Bardet-Biedl syndrome (BBS). Other members of this family were affected either with ML-III, or with BBS. It seems that this unique combination is probably coincidental. PMID- 2240461 TI - Biochemical and morphological studies of dorsal root ganglion and its cultured cells from twitcher mouse (murine globoid cell leukodystrophy). AB - The biochemical pathogenesis of globoid cell leukodystrophy (GLD) (Krabbe disease) was investigated in vitro using the cultured neural cells obtained from dorsal root ganglion (DRG) of twitcher mouse (murine Krabbe disease). Electron microscopic examination of twitcher DRG of 30 days old showed the demyelination and abnormal inclusion bodies, whereas mitochondrial structure appeared to be intact. Cultured neural cells from control mice were well proliferated to form the network processes, while those from twitcher were decreased in cell numbers and showed the vacuolation of cell body, degeneration of processes, and finally died after three weeks. There was no apparent difference of lipid composition between control and twitcher DRG, and the galactocerebroside levels from control were similar to those of twitcher. However, marked accumulation of psychosine was found in the 30-day-old-twitcher DRG. The level of psychosine from twitcher DRG was elevated approximately 70 to 80-fold compared with those of control. These data suggest that neural cells from twitcher mice degenerative with age also in vitro and accumulation of psychosine in twitcher DRG may play an important role for the demyelination in GLD. PMID- 2240463 TI - Ocular manifestations in Fukuyama type congenital muscular dystrophy. AB - We describe a child with Fukuyama type congenital muscular dystrophy (FCMD) who had several ocular manifestations since birth. These included high myopia, strabismus, nystagmus and optic atrophy of both eyes. Later he developed retinal detachment of both eyes. Our survey of 33 cases with FCMD revealed that high myopia and optic atrophy are common in FCMD. Retinal detachment was reported in two cases in addition to the present one and was considered to be of developmental origin. The association of congenital muscular dystrophy with brain changes and ocular anomalies were found in FCMD, muscle, eye and brain disease (MEB) and Walker-Warburg syndrome (WWS). Ocular manifestations in FCMD were, in general, less severe than those in WWS or MEB. Our study suggests that FCMD, MEB and WWS are developmental abnormalities with a continual spectrum of disease severity. PMID- 2240462 TI - The effect of L-carnitine supplementation in 4 pentenoic acid treated rats. AB - The effects of prolonged administration (7 days) of 4 pentenoic acid (4PA, 20 mg/kg/day) or 4PA (20 mg/kg/day) with L-carnitine (200 mg/kg/day) on carnitine metabolism and morphological changes of liver mitochondria were assessed in rats. 4PA-treated rats showed hyperammonemia, decreased levels of blood glucose, free fatty acids and beta-OH-butyrate, and of free carnitine in serum, muscle and liver, increased excretion of acylcarnitine in urine, and enlarged mitochondria with microvesicular steatosis, when compared to saline-injected control rats, respectively. 4PA plus L-carnitine rats showed decreased levels of blood ammonia and increased levels of beta-OH-butyrate, compared to the 4PA group. On the other hand, the levels of free carnitine in serum and liver in rats treated with both 4PA and L-carnitine were increased, when compared to controls. The ratio of acylcarnitine to free carnitine excreted in urine in 4PA-treated rats was higher than that in either the control or 4PA plus L-carnitine group. The liver mitochondria in the 4PA plus L-carnitine group were the same as in the controls. The results suggested that the abnormal biochemical and morphological findings due to only 4PA may be relieved with L-carnitine supplementation. PMID- 2240464 TI - Complete external ophthalmoplegia in a patient with congenital myopathy without specific features (minimal change myopathy). AB - An 11-month-old female infant with mild asphyxia at birth had severe generalized muscle hypotonia and weakness, predominantly in the neck flexors, a high-arched palate and a funnel chest from early infancy. Her facial muscles were also markedly involved. In addition, she showed striking non-progressive, complete external ophthalmoplegia and mild ptosis. A muscle biopsy specimen showed non specific myopathic changes, including mild variation in fiber size, mild type 1 fiber predominance, type 2B fiber deficiency and slightly increased acid phosphatase activity. Complete ophthalmoplegia may thus be seen not only in myotubular myopathy but also in various forms of congenital non-progressive myopathy. PMID- 2240465 TI - A serial muscle biopsy study in a case of congenital fiber-type disproportion associated with progressive respiratory failure. AB - The muscle fiber diameter and distribution were studied in serial muscle biopsy specimens taken at the ages of 21 months and 8 years in a girl with congenital fiber type disproportion. The patient was floppy from birth and showed delayed motor development. Progressive respiratory failure developed from the age of 8, which required artificial respiration during the night. The mean diameters of type 1 fibers at the ages of 21 m and 8 y were 10 mu and 21 mu, and those of type 2 fibers 32 mu and 61 mu, respectively. Whereas most type 1 fibers were hypotrophic in both biopsy specimens, a small number of type 1 fibers (approximately 15%) were normal-sized or hypertrophic, measuring 50 to 90 mu, in the second biopsy specimen, which were thought to have arisen on the maturation of normal-sized or hypertrophic type 1 fibers measuring 15 to 35 mu in the first biopsy specimen. Excessive hypotrophy of type 1 fibers was considered to be responsible for the progressive respiratory failure due to weakness of the diaphragm. The pattern of type 1 fiber evolution from the first to the second biopsy specimen suggested that dysmaturation of spinal motoneurons innervating type 1 muscle fibers would be involved in the pathophysiology of the fiber type disproportion in this case. PMID- 2240466 TI - Brain and liver pathology in a patient with carnitine deficiency. AB - The ultrastructural brain and liver pathology in an infant, who died of acute encephalopathy due to systemic carnitine deficiency (CD), an important condition mimicking Reye's syndrome (RS), was reported. The major finding in the brain was swelling of astrocyte cytoplasm. Expanded mitochondria in nerve cells and myelin sheath splitting in the white matter, which have been reported to be specific to RS, were not observed. Also in contrast to findings in RS, hepatocytes were filled with macrovesicular fat droplets without expanded mitochondria. These findings suggest significant differences in the pathophysiology of acute encephalopathy in CD and RS, although the clinical and laboratory findings during an episode of acute encephalopathy in the former are usually very similar to those in the latter. PMID- 2240467 TI - A possible Japanese male case of Pelizaeus-Merzbacher disease. AB - A boy with an abnormal auditory brain stem response showing only a wave I-II pattern, congenital nystagmus, psycho-motor retardation, pyramidal tract signs and muscular hypotonia was reported. The auditory brain stem response, short latency somatosensory-evoked potential, somatosensory-evoked potential and visual evoked potential indicated an intramedullary disorder of conduction. Magnetic resonance imaging revealed marked high signal intensity of the cerebral white matter in T2-weighted images, suggesting hypomyelination. A muscle biopsy specimen showed neurogenic changes with mild myogenic changes. PMID- 2240468 TI - Plasma PIVKA-II levels in epileptic patients. PMID- 2240469 TI - Radiological colpocephaly. PMID- 2240470 TI - Ex vivo chemopurging of autologous bone marrow with 4-hydroperoxycyclophosphamide to eliminate occult leukemic cells. Laboratory and clinical observations. AB - The application of autologous bone marrow transplantation (ABMT) in treating acute leukemias in children has been limited by the presence of residual occult viable leukemic cells in the marrow cell suspension. One approach to this problem is the ex vivo treatment ("purging") of the autograft to eradicate these tumor cells yet spare the normal lymphohematopoietic stem cells. Initial studies of acute myeloid leukemia (AML) in a rodent model demonstrated that incubation with 4-hydroperoxycyclophosphamide (4HC), a congener of cyclophosphamide and an active alkylating agent in aqueous solution, could effectively eliminate viable AML cells from marrow cell suspensions without apparent toxicity to normal stem cells. We have conducted clinical trials of ABMT with 4HC-treated marrow in children with acute leukemia in remission; marrow was collected, treated ex vivo with 4HC (100 micrograms/ml), and cryopreserved in liquid nitrogen until reinfusion. Children received pre-ABMT conditioning with either high-dose cyclophosphamide and total body irradiation (CY-TBI) for acute lymphocytic leukemia (ALL) or high-dose busulfan and cyclophosphamide (BU-CY) for AML. Of nine children who underwent ABMT with 4HC-treated marrow for ALL in second complete remission (CR2), all relapsed (eight in the marrow, one in the central nervous system) at a median of 5 months (range, 2-17) after ABMT and all have died with relapsed ALL or as a consequence of its treatment. Twenty-nine children with AML (five in CR1, 24 in CR2) received autografts with chemopurged marrow at a median remission duration of 3 months (range, 2-15). Three patients died from sepsis during aplasia; 10 children (one in CR1 and nine in CR2) relapsed with AML at a median of 7 months (range, 2-23) after ABMT, for an actuarial relapse rate of 47%. Sixteen patients with AML (four in CR1, 12 in CR2) are in unmaintained remission at a median of 16 months (range, 6-102) after ABMT, for an actuarial disease-free survival of 49%. Although ABMT with 4HC-treated marrow appears to have a limited role in the treatment of children with ALL who lack a suitable related donor, the results in AML are encouraging and compare favorably with both syngeneic and allogeneic BMT in similar groups of patients. PMID- 2240471 TI - Immunomagnetic purging of bone marrow: a model for negative cell selection. AB - Many in vitro techniques have been developed for removing cancer cells from the marrow of patients who are to undergo autologous bone marrow transplantation (ABMT). These purging techniques can be classified as immunological or pharmacological. The immunomagnetic technique has been widely used in neuroblastoma patients. It depends on an interaction between target neuroblastoma cells in the marrow and a complex of specific monoclonal antibodies and magnetized microspheres, the target cells being selectively removed by passage through a magnetic field. Laboratory studies with neuroblastoma and acute lymphoblastic leukemia cells have shown the high efficiency of this technique in selectively removing cancer cells while retaining adequate numbers of normal hematopoietic cells for subsequent reinfusion into the patient. Clinical studies in several hundred neuroblastoma patients, as well as small numbers of acute lymphoblastic leukemia, breast cancer, and myeloma patients, suggest that this is a clinically safe and effective technique. However, no clinical trial has been conducted comparing ABMT with and without in vitro marrow purging. Until such time, we will regard immunomagnetic purging as "standard of care" for neuroblastoma patients receiving ABMT. PMID- 2240472 TI - Vitamin C deficiency in patients with sickle cell anemia. AB - Because peroxidative damage to red cell membranes may contribute to the pathophysiology of sickle cell disease, deficiency of fat- and water-soluble antioxidants could be a determinant in the pathogenesis of this disease. We have previously reported a deficiency of vitamin E in sickle cell disease. The present study was undertaken to see if a deficiency in vitamin C might also be detected. Leukocyte vitamin C, which reflects total body vitamin C reserve, was measured by a modified 2,4-dinitrophenylhydrazine method. Sickle cell patients (N = 18) had lower leukocyte vitamin C levels (18.3 +/- 9.4 micrograms/10(8) cells) than normal controls (N = 12; 30.3 +/- 7.5 micrograms/10(8) cells; p less than 0.01). Furthermore, 50% of the patients had vitamin C levels below 15 micrograms/10(8) cells, a value consistent with vitamin C deficiency. A statistically significant correlation (r = -0.62 with 0.01 less than p less than or equal to 0.025) was found between leukocyte vitamin C levels and serum ferritin concentration. Because dietary vitamin C intake appeared to be adequate, increased vitamin C utilization may account for this deficiency. However, the mechanisms for this deficiency as well as its pathophysiologic consequences remain to be established. PMID- 2240473 TI - Planning an exchange transfusion in patients with sickle cell syndromes. AB - Partial exchange transfusions are performed in sickle cell patients for a variety of reasons. An algorithm to plan a nonautomated exchange in patients with sickle cell syndromes was developed and validated by a study of 40 such procedures. Formulas that can be used to explore alternatives, by assessing at any point during the exchange the current concentration of sickleable cells and the hematocrit, were devised: a computer program in BASIC is available for maximum versatility. The two most important determinants of the exchange are the patient's initial hematocrit and the desired final concentration of sickleable cells; the rate and type of exchange (continuous or discontinuous) are not important. The final hematocrit depends on the type of blood product used. An exchange can be performed with packed red blood cells (PRBC), whole blood (or its equivalent, PRBC reconstituted with albumin), or it can be started with PRBC and continued with whole blood. Whole blood decreases the concentration of sickeleable cells rapidly and increases the hematocrit slowly; it does not markedly increase the viscosity. PRBCs decrease the concentration of sickleable cells more slowly and increase the hematocrit faster; thus, they may increase the blood viscosity to dangerous levels. PMID- 2240474 TI - Immunologic classification of acute lymphoblastic leukemia. AB - The study of cell surface antigens in acute lymphoblastic leukemia (ALL) has provided the basic information for classification of ALL into B cell or T cell lineage. Each immunologic type may present at an immature or more mature stage of maturation. This classification has prognostic significance since mature B cell and T cell ALL phenotypes have a worse prognosis, compared to common acute lymphoblastic leukemia-associated antigen (CALLA) positive leukemias that belong to an immature B cell lineage and have the best prognosis. By performing these immunologic studies together with those of molecular biology, it is now possible to establish the precise level of cell differentiation, the point at which the malignant transformation occurred. Further studies may allow correlation of these different maturation stages, thus providing insight into the biologic behavior of lymphoblastic leukemia. PMID- 2240475 TI - A phase II study of diaziquone in children with recurrent or progressive solid tumors. Report from the Childrens Cancer Study Group. AB - Seventy-two children with recurrent, progressive, or metastatic lymphomas and other solid tumors, exclusive of primary central nervous system (CNS) tumors, were treated with aziridinylbenzoquinone (AZQ, diaziquone) at 9 mg/m2/day by 30 min intravenous infusion for 5 days every 3 weeks. Fifty-four patients were evaluable for response. Three partial responses occurred, two in patients with recurrent Hodgkin's disease and one in a patient with intraocular retinoblastoma. Sufficient numbers of patients with osteosarcoma, neuroblastoma, and Wilms' tumor were evaluable to demonstrate inactivity of this dosing regimen in these tumor types. Numbers of evaluable patients for other tumor types were insufficient to conclusively demonstrate inactivity. Myelosuppression, which was profound and prolonged, was observed. As administered in this study, AZQ has marginal activity and severe myelotoxicity in children with solid tumors. PMID- 2240476 TI - Splenectomy in compound heterozygous hemoglobinopathies in Saudi Arabia. AB - Hemoglobinopathies are a major public health problem in Saudi Arabia. We studied the effect of splenectomy in 16 Saudi Arabian children with compound hemoglobinopathies. Seven patients no longer require regular blood transfusions, and transfusion requirements were decreased by 30 to 60% in the other eight patients. Three patients whose heights and weights were below the 5th percentile before splenectomy reached the 25th percentile 1 year after the surgery. In spite of preoperative pneumococcal vaccination and the penicillin prophylaxis after the surgery, one patient died of Haemophilus influenzae Group B bacteremia, and three others had six episodes of pneumonia. PMID- 2240478 TI - The bleeding time may be longer in children than in adults. AB - The bleeding time, the most frequently performed test reflecting in vivo platelet function, is the duration of blood flow from a standardized incision on the volar surface of the forearm. Normal values have been determined in adult subjects, but with the exception of neonates, data on the range of bleeding time values in pediatric patients are unavailable. Standard hematology textbooks imply that bleeding time values in children are similar to those of adults. We have reviewed our 9 years of experience with 137 children (mean age 6.5 years) who were referred for diagnostic evaluation of a bleeding disorder but whose history and physical examination were felt by us to be inconsistent with an abnormality of hemostasis. Bleeding time values in these individuals (mean 6.0 min, 95th percentile 9.0 min) were compared with those of 85 normal adult volunteers (mean 4.4 min, 95th percentile 6.5 min). The Simplate-I disposable device and vertical (perpendicular to elbow crease) incision direction were used in both groups. This difference between the pediatric and adult bleeding time values is statistically significant (p less than 0.0001). Neither age nor sex had a significant effect on the pediatric bleeding time measurements. We conclude that the bleeding time, when performed as described, is longer in children than in adults and that pediatric standards for bleeding time should be used in order to avoid a spurious diagnosis of a primary hemostatic disorder in some normal children. PMID- 2240477 TI - Anesthesia for diagnostic and therapeutic procedures in pediatric outpatients. AB - Appropriate sedation of pediatric oncology patients during painful diagnostic and therapeutic procedures is a recognized problem. At the Memorial Sloan-Kettering Cancer Center the pediatric oncologists and anesthesiologists have developed a cooperative program that has provided safe and effective sedation of outpatients. The experience with 100 consecutive outpatients is reported. Patients ranged from 3 months to 17 years of age. Procedures included lumbar puncture and/or intrathecal chemotherapy, multiple bone marrow aspirations, bone marrow biopsies, and removal of indwelling central vein catheters. Monitoring of patients during the procedures as well as various pharmacologic techniques to provide adequate working conditions are described. PMID- 2240480 TI - Successful treatment of acute leukemia with t(4;11) in an infant with congenital hypothyroidism. AB - We describe a case of acute leukemia with t(4;11) (q21;q23) in a 3-month-old girl suffering from congenital hypothyroidism. The blast cells were cytochemically and immunologically classifiable as acute lymphoblastic leukemia of an early B-cell lineage (HLA-DR +, B4 +, CALLA-). but we treated this patient with a protocol designed mainly for acute nonlymphocytic leukemia, employing Adriamycin, vincristine, and cytosine arabinoside. Although the prognosis of this type of leukemia is known to be extremely poor, our patient is currently alive and in continuous complete remission lasting 35 months to date. This case may demonstrate a potential alternative therapeutic strategy for acute leukemia with t(4;11) as well as clinical evidence for the mixed-lineage characteristics of this condition. However, the pathogenetic role of congenital hypothyroidism in the development of acute leukemia is still uncertain. PMID- 2240479 TI - Successful treatment of disseminated Fusarium infection in an immunocompromised child. AB - We report the first know case of disseminated fungal infection due to Fusarium proliferatum in a bone marrow transplant recipient to our knowledge. Fusarium was cultured from the blood, a paranasal sinus, and necrotic skin lesions. The isolate was sensitive to amphotericin B and on further sensitivity testing, synergy was demonstrated using rifampin in combination with amphotericin B. The patient had this infection while she was receiving alternate-day amphotericin, rifampin, and 5-flucytosine (5-FC) therapy. The infection was documented within 48 h of discontinuing daily granulocyte transfusions, which she had received for 3 weeks. The 5-FC was discontinued when sensitivities showed the organism resistant. After 6 weeks of treatment she showed complete remission of the infection, although neutrophil counts remained below 0.25 X 10(9)/L. From this case and from a review of the literature, it appears that synergic antifungal agents combined with leukocyte transfusions may be beneficial in the successful treatment of fusariosis in the compromised host. PMID- 2240481 TI - Polyfungal systemic infections in pediatric oncology patients. AB - Three cases of two fungal agents causing simultaneous systemic infection in immunocompromised pediatric patients are presented and the literature is reviewed. All three patients had several underlying factors that predispose to systemic fungal infections. A species of candida was identified initially as an etiologic agent in all of the three patients causing subcutaneous abscesses, urinary tract infections, fungemia, catheter exit site infection, or pneumonia. However, a few days later blood cultures grew aspergillus species in two of the three patients; in the third patient aspergillus was identified on microscopic examination of the spleen. All three patients had an associated bacteremia with either Staphylococcus aureus or S. epidermidis requiring vancomycin therapy. Presence of aspergillus infection required treatment with amphotericin. Difficulties in making a definitive diagnosis of systemic fungal disease may explain paucity of reports in the literature with simultaneous polyfungal systemic infection. PMID- 2240482 TI - Treatment of neonatal aortic thrombosis with urokinase. AB - We describe the successful treatment of a neonate with severe aortic thrombosis using systemic urokinase. Current knowledge regarding the treatment of this condition, including fibrinolytic therapy, is reviewed. PMID- 2240483 TI - Cystic fibrosis in a black child with hemoglobin S-D disease. AB - A 9-year-old black patient with the simultaneous occurrence of cystic fibrosis and hemoglobin S-D disease is reported. She was placed on chronic transfusion therapy from 1 year of age because of her rapidly worsening pulmonary condition. Her pulmonary function is now stable. The role of this therapy in the overall management of this unusual syndrome is discussed. PMID- 2240484 TI - Immune status in two brothers with Omenn's syndrome: no discernible chimerism on FACS analysis using a monoclonal antibody specific for a maternally restricted HLA antigen. AB - Sequential immunologic examinations, including lymph node biopsies, in two brothers with clinical characteristics of Omenn's syndrome are presented in this study. Although the number of circulating T cells with mature phenotype (OKT3+, TCR1+) was within normal range, the lymphocyte proliferative response to mitogens was poor. Examinations of the lymph nodes revealed marked lymphoid depletion associated with eosinophilic infiltration and reticular cell proliferation. Over the clinical course of 5 months, circulating T cells also mostly disappeared. Thymic hypoplasia was noted at autopsy. Although intrauterine graft-versus host disease (GVHD) has been hypothesized as being the pathogenetic mechanism in this syndrome, maternal lymphocytes circulating in these patients were not identified either by karyotype and HLA typing or by highly sensitive FACS analysis and immunohistochemical studies using a monoclonal antibody, HLA-A9, specific for a maternally restricted HLA antigen, Aw24. In conclusion, the familial occurrence and the absence of maternal chimerism might be the essential features of Omenn's syndrome which should be differentiated from fetal GVHD. PMID- 2240485 TI - Therapy for childhood non-Hodgkin's lymphomas, nonlymphoblastic type. Review of recent studies and current recommendations. AB - Childhood non-Hodgkin's lymphomas can be divided into two broad groups based on histologic findings: lymphoblastic and nonlymphoblastic. Lymphoblastic lymphomas often appear with a mediastinal mass and have a propensity for relapse in the bone marrow and CNS. Nonlymphoblastic lymphomas occur primarily in the abdomen and head-neck region. Relapses tend to occur within the first year and may be either local or systemic. Marrow and/or CNS involvement at diagnosis, bulk disease (reflected as elevated serum lactic dehydrogenase levels), and mediastinal occurrences are adverse prognostic features for nonlymphoblastic lymphomas. Chemotherapy is the treatment of choice for both types of childhood non-Hodgkin's lymphomas. In general, radiation therapy is not necessary for optimal treatment of these tumors. Localized non-Hodgkin's lymphomas of either histologic type are highly curable with short-course chemotherapy. Disseminated non-Hodgkin's lymphomas, particularly those with marrow and/or CNS involvement, remain a major treatment challenge. PMID- 2240486 TI - Problems in diagnosing and treating childhood hematopoietic malignancies in Cameroon, West Africa. PMID- 2240488 TI - Pain management case reports. PMID- 2240487 TI - Advances in anterior cruciate ligament surgery. AB - The anterior cruciate ligament is the most frequently torn ligament in the knee. Diagnosis of cruciate ligament tears is often a difficult task. Tests typically used in diagnosis are the anterior drawer test, Lachman's test, pivot shift test, and the flexion rotation drawer. Arthroscopy has increasingly become the standard for the diagnosis of anterior cruciate ligament tears. Management of these tears has been controversial. The diagnostic techniques are discussed and a surgical technique is described for anterior cruciate ligament reconstruction as an outpatient procedure. The middle one-third of the patellar tendon is used as a graft, harvested subcutaneously, and fixed with interference fit screws. The postoperative function of anterior cruciate ligament deficient knees has been quite satisfactory. Morbidity is decreased relative to open surgical inpatient procedures. Finally, overall cost to the patient has been significantly reduced. PMID- 2240489 TI - An interview: Louis W. Sullivan, M.D. PMID- 2240490 TI - History of medicine in Alaska. M. Walter Johnson, M.D. PMID- 2240491 TI - Glimpses of Alaskan medical history. The notebook of a ship's doctor (1816-17). PMID- 2240492 TI - Trends and patterns of postneonatal mortality in Alaska 1977 through 1984. AB - Several determinants of Alaska postneonatal mortality rate were examined to determine whether very low birth weight (less than 1500 g) and low birth weight (1500-2499 g) surviving neonates contributed to the lack of improvement in postneonatal mortality rate. For an eight year period (1977 through 1984), all infant deaths (n = 1020) of the 82,301 resident births were reviewed through vital statistics data. The infant's place of birth, ethnic group, birth weight and age at death were available. Ethnic and rural-specific postneonatal mortality rate (PNMR) significantly improved, but there was no change in birth weight distribution or birth weight-specific postneonatal mortality rate. However, surviving very low birth weight infant proportion of postneonatal mortality has increased from 5% to 8.2% and low birth weight proportion has remained unchanged (15.6%). These proportions were not offset by the decline in normal birth weight (greater than 2500 g) postneonatal mortality rate. This trend suggests that infants born weighing less than 2500 g have slowed the decline of the postneonatal mortality rate. PMID- 2240493 TI - Anaesthetists and trauma. PMID- 2240494 TI - Admissions to the intensive care unit after complications of anaesthetic techniques over 10 years. 2. The second 5 years. AB - Compared with the first 5 years there was a 19% increase in general anaesthetics, a 171% increase in local and (or) sedation techniques and a 9% increase in obstetric epidurals with no increase in anaesthetic staffing. In this second 5 year period, 46 patients were admitted to the Intensive Care Unit as a result of a complication of an anaesthetic technique. These patients represented 1 in 2371 anaesthetic techniques carried out in the District compared with the previous 5 years where the incidence was 1 in 1543. Seven patients died (15.2%). The complication was considered to be wholly or partially avoidable in 14 instances (30.4%). Four of these subjects died. PMID- 2240495 TI - Behaviour of small children before induction. The effect of parental presence and EMLA and premedication with triclofos or a placebo. AB - The effect of the prescription of triclofos 70 mg/kg orally 90 minutes before operation on the behaviour of 263 children aged 1 to 5 years was studied in a blind, randomised, placebo-controlled trial. EMLA was applied to the dorsum of one hand when the premedication was administered, and all the children were accompanied by a parent during induction of anaesthesia. The frequency of satisfactory behaviour was significantly higher in the triclofos group (p less than 0.02), but the time spent in the recovery ward was increased. PMID- 2240496 TI - Blood contamination of anaesthetic and related staff. AB - The incidence of skin contamination of anaesthetic and related staff by patient's blood and saliva was studied during 270 anaesthetics in Cardiff hospitals over seven continuous days in October 1989. A survey was also made of current Hepatitis B immunisation status and glove-wearing habits of 75 anaesthetists. Blood from 35 (14%) patients caused skin contamination of 65 staff during 46 incidents. Twenty-eight (61%) of the contamination incidents occurred during vessel cannulation. Five (8%) of the 65 staff contaminated by blood already had cuts on their hands. There were nine incidents (4%) of skin contamination by saliva. Fifty-three (71%) anaesthetists were immunised against Hepatitis B. Only seven (9%) anaesthetists wear gloves for oral or nasal intubation, six (8%) for insertion of peripheral venous cannulae, 47 (63%) for insertion of arterial lines and 67 (89%) for insertion of central lines. All anaesthetic and associated staff should wear gloves on a routine basis. PMID- 2240498 TI - Treatment of atelectasis of upper lung lobes. Selective bronchial suctioning with J-shaped catheter tip and guide mark. AB - We developed a technique for blind bronchial suction using a curved-tip catheter with a guide mark, for the treatment of atelectasis of the lower and middle lobes of the lung. Suction of the upper lobe bronchi could not be performed because of the combination of the peculiar anatomy of the upper lobe bronchi with catheter design. We treated successfully two cases of atelectasis of the right upper lobes using a Rusch Metras bronchography catheter with a guide mark which is not readily available. Therefore we devised a J-shape tipped catheter with a guide mark. We have successfully treated 13 episodes of atelectasis of the right upper lobe in 10 patients and one episode in the left upper lobe in one patient with this new catheter. PMID- 2240497 TI - Clinical presentation of suspected malignant hyperthermia during anaesthesia in 402 probands. AB - As anaesthetists have become more aware of malignant hyperthermia the mortality rate has fallen, but concommitantly the number of dubious and aborted cases has increased. All probands who developed a suspected malignant hyperthermia reaction during anaesthesia and subsequently underwent muscle biopsy were classified according to the clinical presentation. A probability for malignant hyperthermia can be calculated, using the classification, for each type of clinical presentation; this varied from 0.96 to 0.07. Certain clinical features were found to be of more value as predictors than others; these included a high creative kinase and myoglobinuria. The accuracy of prediction depends on a clear contemporaneous description of the clinical events. PMID- 2240499 TI - Spinal catheter anaesthesia for caesarean section in a patient with spina bifida. AB - A patient with grossly deformed vertebral anatomy, scheduled for elective Caesarean section, expressed her wish to stay fully awake during the procedure. Epidural anaesthesia was considered to be impracticable, while dural puncture appeared possible only at thoracic level. Spinal anaesthesia using a subarachnoid catheter placed at T7-8 was employed successfully. PMID- 2240500 TI - Severe hypotension due to intramyometrial injection of prostaglandin E2. AB - Treatment of postpartum haemorrhage because of uterine atony with intramyometrial prostaglandin E2 1 mg, in an anaesthetised patient resulted in life-threatening hypotension. Anaesthetists should be aware of the potential cardiovascular side effects of prostaglandins. PMID- 2240501 TI - Laryngeal oedema from a neck haematoma. A complication of internal jugular vein cannulation. AB - Laryngeal oedema occurred after formation of a neck haematoma after attempted internal jugular vein cannulation. This resulted in complete respiratory obstruction and respiratory arrest and it was impossible to ventilate her lungs manually or intubate her trachea. Oxygenation of the patient was only possible using transtracheal ventilation. PMID- 2240502 TI - Mechanical ventilation during low-flow anaesthesia. Experience with an alternative to the bag-in-bottle. AB - Clinical experience with low-flow anaesthesia during controlled ventilation of the lungs is described. The anaesthesia circle is separated by a corrugated hose that serves as a large deadspace. This open connexion has no bellows or overflow valve and therefore the risk of mechanical dysfunction is small. No mixing of circle and ventilator gas occurs during normal operation. Major decreases in the oxygen concentration in the system are unlikely even if the fresh gas flow is interrupted or significant leaks from the circle occur because 100% oxygen is delivered by the ventilator. A hose volume larger than 1650 ml prevented gas mixing at tidal volumes of 380-1170 ml. There was no system-related mishap in over 600 patients, who comprised about 40% of the neurosurgical patients anaesthetised during that period. The cost of isoflurane was reduced to about 33% of that incurred during previous periods. PMID- 2240503 TI - The Woolley and Roe case. A reassessment. AB - In 1953, two patients, Cecil Roe and Albert Woolley, sued their anaesthetist for alleged negligence because they had developed painful spastic paraparesis after spinal anaesthesia. The court found that phenol, which was used to sterilise the outside of the ampoules of local anaesthetic, had percolated the glass through invisible cracks, contaminating the solution, but that the anaesthetist could not have been aware of this risk. The case was important, despite the fact that judgement was in favour of the anaesthetist, because of the fears that it generated over the incidence of paralysis after spinal anaesthesia. The 'invisible crack' theory has been the subject of much scepticism. New information has been obtained, and the case re-examined objectively. The most probable source of contamination, which led to paralysis in the two patients, and in a third who received spinal anaesthesia on the same day, has been identified. A similar explanation may lie behind a number of other episodes of paralysis associated with spinal anaesthesia. PMID- 2240504 TI - Total intravenous anaesthesia with propofol and buprenorphine. AB - A combination of propofol infusion and two bolus doses of buprenorphine, 2.5 or 5.0 micrograms/kg were evaluated in a total intravenous anaesthesia technique in 36 patients of ASA grade 1 or 2 undergoing cholecystectomy. Additional boluses of propofol were given intravenously if needed. Systolic blood pressure after tracheal intubation increased significantly only in those who received the smaller dose of buprenorphine. Patients in both groups remained haemodynamically stable throughout surgery with minimal side effects. Recovery was fast even with prolonged infusions and without major side effects. No patient reported awareness on postoperative questioning. PMID- 2240505 TI - Oral premedication in children. A comparison of trimeprazine with a trimeprazine, droperidol and methadone mixture. AB - One hundred children who presented for minor general surgical procedures were randomly assigned to receive one of two oral premedications. Those in group A (n = 50) were given 3 mg/kg of trimeprazine and those in group B (n = 50) a mixture of trimeprazine 1.0 mg/kg, droperidol 0.15 mg/kg and methadone 0.08 mg/kg. Patients in group B were more likely to be asleep on arrival in the anaesthetic room (p less than 0.02) and were less likely to be distressed at induction of anaesthesia (p less than 0.02). Thiopentone requirements were less in group B (p less than 0.001). The incidence of side effects was similar in the two groups. It is concluded that the mixture produces more satisfactory sedation than trimeprazine. PMID- 2240506 TI - Anaesthesia for cardioversion. A comparison between propofol, thiopentone and midazolam. AB - This study compares the induction and recovery characteristics, haemodynamic changes and side effects of propofol, thiopentone and midazolam when used as the anaesthetic agents for cardioversion. Recovery after midazolam was significantly longer (p less than 0.05) than with either thiopentone or propofol. There was no difference in the recovery times between thiopentone and propofol. There was a significant decrease in mean arterial pressure 2 minutes after induction with propofol and midazolam. Three patients each in the thiopentone and propofol groups needed assisted ventilation because of apneoea, and four patients each in the propofol and midazolam groups had low Spo2 values (less than 95%). Flumazenil was used to reverse the effects of midazolam in eight patients and five of these were still drowsy 4 hours after the procedure. This study indicates that thiopentone is the most satisfactory agent for anaesthesia for cardioversion. PMID- 2240507 TI - Minitracheotomy: complications and follow-up with fibreoptic tracheoscopy. AB - Complications and changes in tracheal mucosa after minitracheotomy were evaluated in 28 patients. Tracheal mucosa was inspected fibreoptically after the insertion of a minitracheotomy cannula, and then at 3-day intervals until the cannula was removed. Thereafter, assessments were made every third day until the mucosa was considered normal. Three significant complications occurred: mediastinal puncture, paratracheal entrance of the cannula and subcutaneous emphysema. Difficulties at insertion of the minitracheotomy cannula were encountered in 15 of 28 patients (54%). Air flow detected through the cannula in one patient, and lack of air flow in another patient, were misleading signs of the position of the cannula. Passing a suction catheter in three patients and a normal end-tidal carbon dioxide tracing in one patient, were also found to be misleading. The correct position and possible complications could be verified only by fibreoptic tracheoscopy. Changes in the tracheal mucosa were independent of the duration of minitracheotomy therapy. PMID- 2240508 TI - Failure of nitrous oxide supply to theatre pipeline system. PMID- 2240509 TI - Aspiration of hot tea. PMID- 2240510 TI - Pulse oximetry and methylene blue. PMID- 2240511 TI - Dosage or concentration. PMID- 2240512 TI - Day-case ophthalmic surgery: general or local anaesthesia? PMID- 2240513 TI - Postoperative hypoxia. PMID- 2240514 TI - Anaesthetic morbidity from trauma to the uvula. PMID- 2240515 TI - The requirement of intensive care support for the pregnant population. PMID- 2240516 TI - APACHE II expected outcome calculations are subject to inter-observer variation. PMID- 2240517 TI - Unpleasant sequelae of benzodiazepine sedation. PMID- 2240518 TI - Opioid supplementation during propofol anaesthesia. PMID- 2240520 TI - Will we ever learn? PMID- 2240519 TI - Partial obstruction of the laryngeal mask airway. PMID- 2240521 TI - A modified Intavent laryngeal mask for ENT and dental anaesthesia. PMID- 2240522 TI - A supraglottic oropharyngeal airway. PMID- 2240523 TI - The laryngeal mask airway and facial burns. PMID- 2240524 TI - The use of a laryngeal mask airway for CT radiotherapy planning and daily radiotherapy. PMID- 2240525 TI - Fibreoptic intubation and double-lumen tubes. PMID- 2240526 TI - Laryngeal mask airway for emergency tracheostomy in a neonate. PMID- 2240527 TI - Pulmonary artery catheter occlusion. PMID- 2240529 TI - Anaesthesia for cataract surgery--time for change? PMID- 2240528 TI - Obstruction in a pressure line. PMID- 2240530 TI - Effects of famotidine and cimetidine on plasma levels of epidurally administered lignocaine. AB - The effects of two H2-receptor antagonists, famotidine and cimetidine, on the plasma levels of epidurally administered lignocaine were studied. Group A (n = 20) received famotidine 20 mg orally the night before surgery and 20 mg intramuscularly 60 minutes before induction of anaesthesia. Group B (n = 15) received cimetidine 200 mg orally the night before the surgery and 400 mg orally 60 minutes before the anaesthetic induction. Group C (n = 20) received neither famotidine nor cimetidine and served as controls. Twelve millilitres of 2.0% lignocaine with adrenaline 1:200,000 was injected into the epidural space in all patients, after the establishment of general anaesthesia with nitrous oxide, oxygen, and enflurane (0.3-0.5%). The patients who received cimetidine showed significantly higher plasma concentrations of lignocaine compared with either group A or group C at all investigation times (p less than 0.01). The mean peak plasma concentrations were 2.4 (SEM 0.1), 3.2 (SEM 0.2) and 2.3 (SEM 0.1) micrograms/ml in group A, B, and C, respectively. This study suggests that famotidine is preferable to cimetidine for control of gastric acidity before the use of lignocaine as the epidural anaesthetic. PMID- 2240531 TI - Epidurography in premature infants. AB - A caudal epidural catheter was inserted in 20 premature, high risk infants for abdominal or thoracic surgery under combined caudal epidural and general anaesthesia. Epidurography was used to confirm the position of the catheter which was found to be misplaced in three patients. The catheter penetrated the dura in one case, in another the tip was located in an epidural vessel and in the third the catheter was seen to be curled up within the epidural space. It was concluded that epidurographic control is essential with this method of anaesthesia in very small infants, in whom it was found to provide considerable advantages despite serious risks. PMID- 2240532 TI - Anaesthetic problems in ex situ resection of the liver. AB - Ex-situ resection of the liver is a new surgical technique for treatment of liver tumours not amenable to conventional surgery. This paper describes the cardiovascular and metabolic changes that occurred in nine consecutive such patients. No severe haemodynamic or pulmonary complications occurred. Specific problems were encountered during the prolonged anhepatic period, which lasted an average of 5.96 (SD 1.46) hours. Significant metabolic and coagulation disorders occurred 2 to 3 hours after hepatectomy because of complete loss of hepatic function. The predominant findings during the anhepatic period were hypoglycaemia and severe metabolic acidosis, mainly from increased levels of lactic acid. Exogenous administration of dextrose 5% at an average rate of 188 ml/hour was necessary to maintain normoglycaemia, while correction of metabolic acidosis required 403 (SD 159.79) mmol of sodium bicarbonate, supplemented by hyperventilation. Tris-hydroxymethylaminomethane was used when sodium overload was thought to be a problem. There was a marked decrease of Factor V and fibrinogen, a moderate thrombocytopenia and fibrinolysis. The severity of these alterations was dependent on the duration of the anhepatic period and the primary function of the re-implanted liver. PMID- 2240533 TI - Combined air and oxygen entrainment. Effect on the percentage output of fixed performance masks. AB - Secondary oxygen was added to air entrained by the primary jet of a fixed performance mask. Twenty such masks, in each of six groups rated at 24%, 28%, 31%, 35%, 40% and 50%, gave higher O2 percentages equivalent to those calculated from an equation that related the O2 concentration to the secondary flow. Actual values of both were closely correlated, with regression slopes and intercepts similar to those derived from this equation. This technique is simple and predictable in altering the composition of an air-oxygen mixture delivered to the patient. PMID- 2240534 TI - Loss of consciousness after emergence from anaesthesia. A case of suspected micturition syncope. AB - A case of postanaesthesia micturition syncope with respiratory arrest is described. If syncope occurs, the temporary myocardial ischaemia and cerebral hypoperfusion may increase anaesthetic risk in the marginally compensated patient. The loss of airway protection during the syncopal period is also a cause of concern. We recommend the use of an indwelling bladder catheter during any prolonged surgical procedure. PMID- 2240535 TI - The Engstrom Elsa anaesthetic machine. An electronic system for anaesthesia. AB - Six Engstrom Elsa anaesthetic machines have been in regular use for 18-24 months. The machine incorporates a number of new concepts for anaesthetic delivery and monitoring. At flows below 1000 ml/minute, each machine delivered 20% more than the indicated value; at higher flows, the indicated value was within 10% of the flow delivered. Minute volume, tidal volumes and oxygen concentrations were within the manufacturer's specifications. However, vaporizer and vapour monitor performance was outside the (SD) 5% accuracy claimed by the manufacturers. It was noted that the bistable valve requires user familiarity for the change from controlled to spontaneous ventilation to be accomplished with ease. It was also possible to misconnect the breathing system and so isolate the excess pressure escape valve and high-pressure alarm. Nevertheless, once familiarisation was achieved, the machines have proved easy to operate and are particularly satisfactory when used with low fresh gas flows. PMID- 2240536 TI - Resistance to fluid flow through two spinal needles. AB - A new needle, 120 mm long and 26 gauge in diameter, has been introduced for subarachnoid anaesthesia. The resistance to flow through the needle was measured using a pressure monitor infusion pump and compared with the resistance to flow through a 90-mm 26-gauge needle; there was a threefold increase in resistance in the 120-mm needle compared to the 90-mm needle, which could not be explained by the difference in length alone and must reflect a decrease in the internal diameter of the long needle. This results in difficulty in identifying the subarachnoid space by backflow of cerebrospinal fluid. PMID- 2240537 TI - Another Selectatec switch malfunction. AB - Malfunction of a Selectatec-3 switch mechanism is reported which caused isolation of the selected vaporizer. This resulted in a delivery of unsupplemented fresh gas to the patient. PMID- 2240538 TI - The Trilite inhaler. An historical review and performance assessment. AB - The Trilite inhaler was developed for use in World War II. Its efficient performance is confirmed and a brief biography of its inventor is also given. PMID- 2240539 TI - Intravenous diclofenac sodium. Does its administration before operation suppress postoperative pain? AB - Intravenous diclofenac sodium was evaluated in a double-blind randomised trial relative to intramuscular diclofenac, intravenous fentanyl, and intramuscular placebo in 160 patients undergoing extraction of impacted lower third molar teeth. The test drug was administered before operation in an attempt to alleviate postoperative pain. A 10-cm visual analogue scale was used to assess pain at 30 minutes and one day after surgery, if the patients stayed overnight. Patients who received intravenous diclofenac had significantly less pain than the other groups 30 minutes after operation. They also had significantly less pain one day after surgery than the placebo or opioid groups, but not less than the intramuscular diclofenac group. Capillary bleeding time, in comparison with placebo, was significantly prolonged after the use of intramuscular diclofenac, and a similar but nonsignificant trend was observed in the intravenous diclofenac group. No problems were encountered with excessive bleeding in any group. PMID- 2240540 TI - An evaluation of a 30-gauge needle for spinal anaesthesia for caesarean section. AB - A 30-gauge spinal needle was evaluated for Caesarean section, using a combined epidural/spinal technique, in 50 mothers. Spinal anaesthesia failed in six mothers and was inadequate in another six. General anaesthesia was required on one occasion. A 25% overall failure rate suggests that a 30-gauge needle is not a practical proposition for routine clinical practice. PMID- 2240541 TI - Intrathecal anaesthesia for day-care surgery. A retrospective study of 160 cases using 25- and 26-gauge spinal needles. AB - The records of 160 day-care surgical patients who received intrathecal anaesthesia were reviewed. No major complications were recorded. The incidence of postspinal headache after puncture with a 25-gauge spinal needle was nearly four times more frequent compared to a 26-gauge needle. The occurrence of postspinal headache in patients over the age of 45 years was significantly less frequent (p less than 0.05) than in younger patients. Intrathecal anaesthesia was acceptable to 91% of outpatients in this group. PMID- 2240543 TI - Successful difficult intubation. Tracheal tube placement over a gum-elastic bougie. AB - A randomised study was carried out to assess the effect of tracheal tube rotation on the passage of a tube over a gum-elastic bougie into the trachea in 100 patients. The effect of the presence or absence of a laryngoscope on successful tube placement was also assessed. A grade 3 difficult intubation was simulated in patients with a laryngoscope. There was a significant difference in the rates for successful first-time intubation in those patients with tube orientation of -90 degrees (with the bevel facing posteriorly) as compared with a tube orientation of 0 degrees (the normal orientation with the bevel facing left). The unsuccessful first-time intubations with a 0 degree orientation were frequently converted to successful intubations with the -90 degrees position at a second attempt. The presence of a laryngoscope in the mouth while rail-roading a tube over the bougie also made a significant difference to the rate of successful first-time intubations. The most successful method was to leave the laryngoscope in the mouth and rotate the tube to -90 degrees. PMID- 2240542 TI - Relief of injection pain in adults. EMLA cream for 5 minutes before venepuncture. AB - The effectiveness of skin anaesthesia after 5 minutes' topical application of a lignocaine-prilocaine cream was evaluated. One hundred and twenty patients estimated the pain of antecubital venepuncture both on a linear scale and verbally after use of the cream for either 5 or 60 minutes, a placebo cream or no treatment. Reported pain was significantly less after only 5 minutes of the lignocaine-prilocaine cream (p = 0.002). The cream can be used to relieve the pain of all routine injections. PMID- 2240544 TI - Acid aspiration prophylaxis in 288 obstetric anaesthetic departments in the United Kingdom. AB - The choice of drugs for acid aspiration prophylaxis in 288 obstetric anaesthetic departments in the United Kingdom was determined by questionnaire. The results are compared with a similar survey of anaesthetic departments 5 years ago. The prescription of sodium citrate and the H2 receptor antagonist ranitidine has superseded that of Mist. magnesium trisilicate. PMID- 2240545 TI - Anaesthesia and the law. PMID- 2240547 TI - Does xenon deserve a prominent place in anaesthetic practice? PMID- 2240546 TI - Children's premedication and hypoxaemia. PMID- 2240548 TI - Crystalloid preloading in spinal anaesthesia. PMID- 2240549 TI - Monitoring during sedation. PMID- 2240550 TI - Management of supraventricular tachycardia in septic patients. PMID- 2240551 TI - Trauma to epidural veins: the role of posture. PMID- 2240552 TI - Convulsions after cocaine and propofol. PMID- 2240553 TI - Electro-acupuncture and postoperative emesis. PMID- 2240554 TI - Problems associated with the introduction of different equipment. PMID- 2240555 TI - The use of transtracheal cannulation after difficult intubation. PMID- 2240556 TI - Laryngeal mask and anaesthetic waste gas concentrations. PMID- 2240557 TI - Laryngeal mask airway for inadequate reversal. PMID- 2240558 TI - Supplementary oxygen and the laryngeal mask airway. PMID- 2240559 TI - Persistent erection and general anaesthesia. PMID- 2240560 TI - The oesophageal detector device and the laryngeal mask. PMID- 2240561 TI - An inappropriate use of tape. PMID- 2240562 TI - Another failure of Selectatec block. PMID- 2240563 TI - [The effect of postural changes on cerebral hemodynamics during general anesthesia]. AB - Anesthesia may compromise the regulation of systemic and cerebral hemodynamics following changes in body position. Sudden decreases in cerebral perfusion pressure due to changes from a horizontal to a head-elevated position may cause decreases in cerebral blood flow (CBF), particularly in patients with preexisting cerebrovascular disease. Transcranial Doppler sonography (TCD) permits on-line measurement of blood flow velocity (BFV) in human basal cerebral arteries, and there is evidence that monitoring of BFV may indicate relative changes in CBF. The present study compares the effects of changes from a horizontal to a head elevated position on blood flow velocity in the middle cerebral artery (MCA) in 30 patients (ASA I) with different levels of steady state anesthesia (group A: n = 20, isoflurane = 1.0 vol% end-tidal; group B: n = 10, isoflurane = 0.4 vol% end tidal; O2/N2O; FiO2: 0.3; 6 1/min). The MCA was insonated by transtemporal approach using a 2 MHz Doppler ultrasound system (TC2-64 B, EME) with a range gating mechanism, adjustable sample volume depth, and flow direction discrimination. Systolic (Vsyst, cm/s) and mean flow velocity (Vmean, cm/s), pulsatility index (PI), mean arterial blood pressure (MAP, mmHg), heart rate (HR, b/min) and end-tidal CO2 (pet-CO2, mmHg) were recorded with the subjects lying flat (baseline values) and for 5 min following adjustment to a 35-40 degrees head elevated position. There was a significant reduction of 25% for Vsyst from 79 +/- 17 cm/s (baseline) to 59 +/- 13 cm/s and a 33% decrease for Vmean from 52 +/- 9 cm/s (baseline) to 35 +/- 9 cm/s in group A immediately after repositioning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240564 TI - [A fatal hypertensive reaction during anesthesia in a patient with acute subarachnoid hemorrhage]. AB - We describe the case of a 55-year-old female patient who presented for clipping of cerebral artery aneurysm that had ruptured 8 h before. Anesthesia induction was uneventful. After adequate positioning of the patient, two injections of a saline solution containing ornipressin (POR 8) were given into the scalp. Before surgical incision the patient developed a hypertensive reaction with arterial blood pressure of 230/140 mm Hg and heart rate 140/min. Pharmacologic intervention decreased the blood pressure and heart rate to normal values within 4 min. Upon surgical opening of the skull, the dura was found to be extremely noncompliant, and the pupils became wide and nonresponsive to light. Acute rebleeding was diagnosed, and the patient was sent back to the intensive care unit without clipping of the aneurysm and was declared brain-dead 12 h later. A Cushing response following acute rebleeding and other factors that might have caused the hypertensive crisis are discussed in detail. Anesthetic agents and adjuncts are assessed in terms of their influence on intracranial pressure and their protective action on the brain. Special consideration is given to subcutaneous ornipressin injection, which is known to be associated with cardiovascular side effects. Deep neuroleptanesthesia is recommended as the anesthetic technique of choice for clipping of cerebral artery aneurysms. Antihypertensive agents without cerebrovascular side effects should be used to treat hypertensive reactions. PMID- 2240565 TI - [Lymphocyte subpopulations in patients at risk of sepsis in a surgical intensive care unit]. AB - Infection remains a major cause of morbidity and mortality in intensive care medicine. The increased susceptibility of the severely injured patient to sepsis and consecutive multiorgan failure has been attributed to abnormalities in cell mediated immunity. The purpose of our study was to determine changes in the pattern of lymphocyte subpopulations in severely injured patients and to relate these changes to any development of sepsis and to outcome (indirect immunofluorescence with monoclonal antibodies). During 14 months we investigated 28 patients (ages 15-65 years) suffering from severe multisystem trauma (22 cases) or diffuse peritonitis (6 cases), 6 of whom (21.4%) developed sepsis and multiorgan failure; 4 of these 6 septic patients died. According to the clinical data, patients developed sepsis between the 3rd and 6th days after trauma. We therefore defined days 1-3 as the preseptic phase, days 3-6 as the phase of sepsis development, and days 4-10 as the phase of septic disease. In the preseptic phase there was no statistically significant difference in the pattern of the eight lymphocyte subpopulations measured between patients who later developed sepsis and those who did not. During the phase of sepsis development, however, the patients who did develop sepsis showed significantly reduced numbers of CD2-, CD8-, and CD20-positive cells (P = 0.0003; P = 0.009; P = 0.012). The number of helper cells (CD4) was also decreased, but the difference between the two groups failed to reach statistical significance (P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240566 TI - [A cost comparison of Pall filters versus chemical or thermal disinfection of ventilator tubes]. AB - Filter manufacturers claim that the use of disposable filters for anesthesia and ventilation therapy would be more economical than changing the tubes and/or ventilation circuits every 24 h or 48 h. We therefore compared the costs of chemical disinfection or thermal disinfection of 4 different ventilation tube systems with those of disposable Pall filters. The cost of disinfecting tubes used for ventilation or anesthesia varies 1.81 DM to 12.60 DM and is therefore lower than that of the use of disposable filters changed daily. Tubes used for anesthesia should be changed after each patient and tubes for ventilation therapy can be changed every other day, but disposable filters must be changed daily or after each case when used for anesthesia. PMID- 2240567 TI - [The handling of propofol (Disoprivan)]. PMID- 2240568 TI - Carbohydrate characterization of recombinant glycoproteins of pharmaceutical interest. AB - Carbohydrate characterization of recombinant glycoproteins entails determination of the primary structures and points of attachment of the oligosaccharide moieties. This article reviews several methods for oligosaccharide- and glycosylation-site characterization. A major recent advance in carbohydrate analysis has been the use of high-pH anion exchange (HPAE) chromatography for separation of glycoprotein-derived oligosaccharides. These separations are sensitive to molecular size, carbohydrate composition, linkage positions, and anomeric configurations. As a result, HPAE chromatography is a powerful technique for glycoprotein characterization and can serve as the basis of an "oligosaccharide map." Characterization of potential N-glycosylation sites involves determining whether each potential site is glycosylated, the extent of oligosaccharide processing at each site, and ideally, a detailed description of the distribution of oligosaccharides at each site. Several approaches to characterizing glycosylation sites are described, including peptide mapping and mass spectrometry. Treatment of a glycoprotein with endo-beta-N acetylglucosaminidase H (endo H) followed by peptide:N-glycosidase F (PNGase F) can be used to distinguish sites that are not glycosylated from those carrying high-mannose structures and from those containing attached complex oligosaccharides. After individual glycosylation sites have been labeled by this series of reaction, the resulting peptides are characterized by automated Edman degradation. This technique is particularly valuable for characterizing peptides that contain more than one potential N-glycosylation site. An example is also given in which HPAE chromatography is used in conjunction with reversed-phase high-performance liquid chromatography tryptic mapping to obtain detailed information on the distribution of oligosaccharides at individual glycosylation sites. PMID- 2240569 TI - Optimization of high-sensitivity fluorescence detection. AB - We present general expressions for the number of photons emitted by a fluorescent chromophore as a function of the intensity and the duration of illumination. The aim is to find optimal conditions for detecting fluorescent molecules in the presence of both ground-state depletion and photodestruction. The key molecular parameters are the absorption coefficient epsilon, the excited singlet-state lifetime tau f, the excited triplet-state decay rate kT, the intersystem crossing rate kI, and the intrinsic photodestruction time tau d. When only singlet saturation and photochemistry are important, the signal-to-noise ratio depends on two fundamental variables: k, the ratio of the absorption rate ka to the observed fluorescence decay rate kf, and tau, the ratio of the duration of illumination taut to the intrinsic photodestruction time tau d. Equations are also developed for the more complicated cases when triplet formation and photochemistry are important. This theory was tested by measuring the fluorescence from a solution of beta-phycoerythrin flowed through a focused argon ion laser beam. The dependence of the fluorescence on the incident light intensity and the illumination time agrees well with the theoretical prediction for singlet saturation and photochemistry. The signal-to-noise ratio is optimal when the light intensity and the flow rate are adjusted so that both K and tau are close to unity (5 X 10(22) photons cm-2 s-1 and a transit time tau t of 700 mus). This analysis should be useful for optimizing fluorescence detection in DNA sequencing, chromatography, fluorescence microscopy, and single-molecular fluorescence detection. PMID- 2240570 TI - Systematic delineation of scan modes in multidimensional mass spectrometry. AB - A logical analysis of mass spectrometric scan modes is performed that reveals the full set of experiments available in multidimensional mass spectrometry. The analysis utilizes a symbolism that helps provide an organizational scheme for the representation and classification of the wide variety of experiments that exist. In general, for an n-stage experiment, there is a closed set of experimental modes producing spectral types that vary in mass dimensionality from 0 to n. There is a total of 2n experiments that have 1 or 0 mass dimensions, along with an increasing number of experiments of higher mass dimensionality. There also exists a set of 2n fundamental scan modes, viz., experiments in which only mass to-charge ratios of individual ions, but not their interrelationships, are specified. Scans in which functional relationships between ion masses are defined (e.g., neutral loss scans) introduce complexity into the total number of scan types available in an MSn experiment, giving a total of 1, 2, 5, 15, 52, and 203 experiments of 0 through 5th order, respectively. It is shown that combinations of data from lower order experiments can be used to construct higher order spectra. Extraction of data of lower mass dimensionality from data of higher dimensionality is also demonstrated. A different method of reducing dimensionality, projection of dispersed data back into a smaller number of mass dimensions, is also introduced and characterized. The analysis reveals several new types of scan modes including an MS/MS/MS scan having unit mass dimensionality, referred to as the selective neutral-loss scan, and several new MS/MS/MS scans that are two-dimensional in mass. Examples of these new experiments are provided, and their potential value is discussed. PMID- 2240571 TI - Long-term performance of a gas chromatography/tandem mass spectrometry assay for tebufelone in plasma. AB - An automated gas chromatography/tandem mass spectrometry (GC/MS/MS) based method for the rapid determination of tebufelone (TE) in animal and human plasma has been routinely applied in our laboratory to more than 3000 samples over a 2-year period. The selectivity of MS/MS conducted on a triple quadrupole instrument, combined with the use of a stable-isotope-labeled internal standard, results in excellent analytical figures of merit, as well as minimal sample preparation, rapid analysis, and high assay reliability. The work described here goes beyond initial method development and validation studies by evaluating the long-term performance of quantitative GC/MS/MS. Electron ionization produces M.+ ions for TE and the [13C, 18O]TE internal standard, which are selected in Q1 and undergo collisionally activated dissociation in Q2. Quantitation is based on monitoring daughter ions at m/z 248 and 251, respectively, in Q3. A linear range of 1-3000 ng of TE/sample (20 pg to 60 ng injected) provides access to an effective concentration range of 0.5-30,000 ppb TE in plasma (0.1-2-g samples). The assay shows no bias and less than 10% relative standard deviation over this range. In the automated mode, less than 7 min elapse from injection to report printout and more than 70 plasma samples are routinely prepared and analyzed in a day. Such performance is consistently maintained throughout long-term application. PMID- 2240572 TI - High-accuracy molecular mass determination of proteins using matrix-assisted laser desorption mass spectrometry. AB - A method for obtaining protein molecular masses with an accuracy of approximately +/- 0.01% by matrix-assisted laser desorption using an internal calibrant is described. The technique allows accurate mass determinations of protein sample sizes as small as 1 pmol. High concentrations of organic and inorganic contaminants (e.g. 1 M urea) do not strongly affect either the signal intensity or the mass assignment. The ability to assign an accurate molecular mass to a protein is contingent on the observation of clearly resolved protonated molecule ions in the mass spectrum. PMID- 2240573 TI - Capillary electrophoresis in 2 and 5 microns diameter capillaries: application to cytoplasmic analysis. AB - Capillary electrophoresis with electrochemical detection in 2- and 5-micron capillaries has been developed to study ultrasmall biological environments. Sample volumes as low as 270 fL have been injected into the electrophoresis capillary with subattomole detection limits for easily oxidized species. We have applied this method to the analysis of single cell cytoplasm. Sampling of the cytoplasm is accomplished by inserting one end of the electrophoresis capillary directly into a single nerve cell. The high-voltage end of the electrophoresis capillary has been etched with hydrofluoric acid to form a microinjector. This injection scheme represents an improvement over those previously used for similar applications. The excellent selectivity of this method is demonstrated for catecholamine and indolamine neurotransmitters and their metabolites found in the invertebrate system, the pond snail Planorbis corneus. PMID- 2240574 TI - Multiple mode semiconductor diode laser as a spectral line source for graphite furnace atomic absorption spectroscopy. PMID- 2240575 TI - Chemical control of reaction time in an enzyme assay and feasibility of enzyme spot tests. AB - There are many circumstances in which the understanding of a patient's status would be improved by knowing one or more enzyme activities. Such data are routinely produced in clinical laboratories, but simple, noninstrumental tests for enzymes are a rarity, so their extralaboratory determination is also rare. The essential problem is that effective clinical determinations of enzyme activities are typically carried out by measuring reaction rates, so the reaction time needs to be controlled. The reaction time of a sample can be controlled by using a passive, ion exchange-based titration. In this work, OH-, H+, and quinidine have been used to stop the enzymes LDH (EC 1.1.1.27) (with H+ and OH-) and cholinesterase (EC 3.1.1.8) (with quinidine). The ion exchange material containing the enzyme-stopping ion is separated from the sample by a filter. The sample contains ions that can exchange with the enzyme-stopping ion in the ion exchange material, and it may contain species that buffer the enzyme-stopping ion. The reaction time is governed by the exchanging ion's concentration in the sample, the quantity of buffer in the sample, the thickness of the filter between the ion exchange material and the sample, and the temperature. A test for LDH requiring 50 microL of serum and no instrumentation can be made so that results from sera with elevated levels appear different than those with normal levels. PMID- 2240576 TI - Selective determination of histamine by flow injection analysis. AB - A flow injection analysis (FIA) method for the determination of histamine is described. Control of reaction timing allows exploitation of a transient, chemical-kinetic increase in selectivity that occurs when o-phthalaldehyde reacts with histamine. The molar fluorescence ratio (selectivity) of histamine/histidine reaches a maximum value of 800 in 32 s, precluding the need for separation of histamine from histidine, spermidine, and other potential interferences in biological samples. On-line dilution prevents matrix effects and affords a linear response up to approximately 4.45 mM histamine, or 500 mg of histamine free base/100 g. Under these conditions the detection limit (3 times peak-to-peak baseline noise) is 5.5 pg (corresponding to 0.60 mg of histamine free base/100 g of sample) and throughput is 60 injections per hour. The high sensitivity and high selectivity of the method allow the rapid determination of histamine in fish with minimal sample conditioning and will find application in the determination of endogenous histamine as well, such as in blood plasma and brain tissue. PMID- 2240577 TI - Noninvasive method for monitoring ethanol in fermentation processes using fiber optic near-infrared spectroscopy. AB - Short-wavelength near-infrared (SW-near-IR) spectroscopy (700-1100 nm) is used for the determination of ethanol during the time course of a fermentation. Measurements are performed noninvasively by means of a photodiode array spectrometer equipped with a fiber-optic probe placed on the outside of the glass wall fermentation vessel. Pure ethanol/water and ethanol/yeast/water mixtures are studied to establish the spectral features that characterize ethanol and to show that determination of ethanol is independent of the yeast concentration. Analysis of the second-derivative data is accomplished with multilinear regression (MLR). The standard error of prediction (SEP) of ethanol in ethanol/water solutions is approximately 0.2% over a range of 0-15%; the SEP of ethanol in ethanol/yeast/water solutions is 0.27% (w/w). Results from the mixture experiments are then applied to actual yeast fermentations of glucose to ethanol. By use of a gas chromatographic method for validation, a good correlation is found between the intensity of backscattered light at 905 nm and the actual ethanol. Additional experiments show that a calibration model created for one fermentation can be used to predict ethanol production during the time course of others with a prediction error of 0.4%. PMID- 2240578 TI - Continuum-source atomic absorption spectroscopy with an echelle spectrometer adapted to a charge injection device. AB - An instrumental system for continuum-source atomic absorption spectroscopy has been developed for simultaneous multielement determinations. The system consists of an electrothermal atomizer and a charge injection device adapted to an echelle spectrometer to achieve multiplex detection. A continuous 40-nm spectral range in the two-dimensional echelle spectrum was acquired simultaneously through the capability of the charge injection device to integrate signals in its MOS capacitors. Novel methods were developed to compute absorbances by "scanning" through all orders in the entire echelle spectrum or selecting absorption lines randomly. In the range 300-430 nm, characteristic concentrations (1% absorption) were 1.6, 2.6, 2.9, and 3.8 ng mL-1 respectively for Cu, Mn, and two Cr lines; these values are similar to those (1.3, 2.2, 1.2, and 3.6 ng mL-1) obtained for single-element detection with an image-dissector system. PMID- 2240579 TI - Resolution of multicomponent fluorescence emission using frequency-dependent phase angle and modulation spectra. AB - We describe a new fluorescence method that allows the resolution of both the decay times and emission spectra of mixtures of fluorophores. This method is completely general and does not require any assumptions or knowledge of the decay times or emission spectra of the individual fluorophores. We use the phase angle spectra and modulation spectra of the mixture, measured over a range of suitable light modulation frequencies and emission wavelengths. These data are analyzed by nonlinear least-squares analysis to recover the emission spectra and the associated decay times. The principle of the method and the nature of the data are illustrated by using two-component mixtures with increasing spectral overlap. We then demonstrate the recovery of minor components, of structure emission spectra, and of a three-component mixture with completed overlapping emission spectra. And finally, we describe the resolution of a two-component mixture with decay times of 0.8 and 1.4 ns using modulation frequencies up to 774 MHz. PMID- 2240580 TI - Enzyme-linked immunosorbent assay compared with gas chromatography/mass spectrometry for the determination of triazine herbicides in water. AB - An enzyme-linked immunosorbent assay (ELISA) was compared to a gas chromatography/mass spectrometry (GC/MS) procedure for the analysis of triazine herbicides and their metabolites in surface water and groundwater. Apparent recoveries from natural water and spiked water by both methods were comparable at 0.2-2 micrograms/L. Solid-phase extraction (SPE) was examined also, and recoveries were determined for a suite of triazine herbicides. A significant correlation was obtained between the ELISA and GC/MS method for natural water samples that were extracted by SPE. Because ELISA was developed with an atrazine like compound as the hapten with conjugation at the 2-position, it was selective for triazines that contained both ethyl and isopropyl side chains. Concentrations for 50% inhibition (IC50) were as follows: atrazine, 0.4 microgram/L; ametryne, 0.45 microgram/L; prometryn and propazine, 0.5 microgram/L; prometon, 0.7 microgram/L; simazine and terbutryn, 2.5 micrograms/L; hydroxyatrazine, 28 micrograms/L; deethylatrazine and deisopropylatrazine, 30 micrograms/L; cyanazine, 40 micrograms/L; didealkylatrazine had no response. The combination of screening analysis by ELISA, which requires no sample preparation and works on 160 microL of sample, and confirmation by GC/MS was designed for rapid, inexpensive analysis of triazine herbicides in water. PMID- 2240581 TI - A supratrochlear foramen in the humerus of cattle. AB - A supratrochlear foramen of the humerus was demonstrated in three Turkish cattle. The average size of the foramen was 1.2 x 0.7 cm. This appears to be a new anatomic finding in the bovine. PMID- 2240582 TI - Immunohistochemical study of peptide-containing nerves in the gastrointestinal tract of the Japanese field vole, Microtus montebelli. AB - The distribution and relative frequency of nerves containing immunoreactivity for substance P (SP), vasoactive intestinal polypeptide (VIP), gastrin-releasing polypeptide (GRP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and menthionine-enkephalin (MENK) were studied by immunohistochemistry in the gastrointestinal tract of the herbivorous Japanese field vole, Microtus montebelli. PMID- 2240583 TI - Differences in fibre population in dog muscles of different functional purpose. AB - Samples were taken from particular sites of the tibialis cranialis (extensor), flexor digitalis medialis (flexor) and pectineus (adductor) muscles of 27 dogs of different breeds--German shepherd, Spanish greyhound, Spanish mastiff and Iberian hound. Samples, which were taken from right and left limbs, were subjected to histochemical analysis using ATPase (pH 9.4, 4.6 and 4.2) and NADH-tr. Fibre population was assessed using an IBAS-2 Kontron image analyser. PMID- 2240584 TI - [The structure of the syrinx in the duck (Anas platyrhinchos)]. AB - The morphological and structural aspects of the Membrana tympaniformis medialis of the syrinx were studied with L.M. and E.M. in 32 female and male Peking ducks from 6 to 12 months old. The membrane is covered by pseudostratified prismatic epithelium which shows different regional features. While at level of the proximal and distal third of the tympanic membrane the morphological and structural aspects of the cells resemble that of the adjacent structures (pessulus and primary bronchi), the middle part of the epithelium layer becomes gradually flattered; the epithelium is made up of oblique or horizontal cells which touch each other by means of many lateral interdigitations. At level of the upper parts of the cells there are several types of cell junctions. This particular disposition seem to be well adapted to the contractions of the syringeal muscles. PMID- 2240585 TI - [The capillarization of the M. pectoralis of the turkey (Meleagris gallopavo) from hatching to the 280th day of life]. AB - The capillarization of the M. pectoralis was examined in the turkey as it changed with age. Examined was the density of the muscles fibers (per mm2), the density of the capillaries (per mm2) and the quotient muscle fibers/capillaries. In accordance with the sequence of the original data four functions of organismic growth (slightly altered) were utilized for the approximation of the data for descending amounts: Putter/Bertalanffy (1920, 1934); Richards (1959); Janoschek enlarged after Sager (1980) and Richards enlarged after Sager (1980). The approximations were made via nonlinear regressions, whereby the sum of the error amounts and the sums of the error squares served as criteria of quality. The results including the deduced initial and end amounts are combined in tables which also contain the parameter of the way the computations were conducted. PMID- 2240586 TI - Neuroendocrine (NE) cells in rat neonatal lungs. A histochemical and immunocytochemical study. AB - A study has been carried out to determine the presence of NE cells in the newborn rat lung. The localization of these cell was achieved by an argyrophil method. Both single NE and NEB, were found. Immunoperoxidase techniques were performed to determine NSE, serotonin and calcitonin production in these NE formations. PMID- 2240587 TI - Morphological, histochemical and ultrastructural features of the globule leukocyte of the bovine respiratory tract. AB - The histochemical and ultrastructural features of the globular leukocyte of the bovine respiratory tract is described and found to be similar to those localized in the abomasum and bile ducts of cattle. Histochemical analysis of these cells demonstrated low amounts of carboxylated mucin mixed with neutral mucin and large amounts of basic protein. Two types of globules were seen in the leucocytes; one with a homegeneous electron dense material and another with vesiculated, crastalloid containing bodies. PMID- 2240588 TI - [The synovial organization of the M. fibularis longus in cats, dogs, swine, cattle, sheep and goats]. AB - The synovial structures of the M. fibularis longus were studied by dissection on 23 cat, 28 dog, 20 pig, 17 ox, 15 sheep and 17 goat limbs. Five injections with Technovit into the tarsometatarsal joint were made for each species. The dog had two tendon sheaths while all other species had only one lateral one. The mesotendon approached the tendon from the medial aspect and was fenestrated in the dog (here only in the proximal segment), pig, sheep, and goat, but in the cat and ox the fenestration was inconstant. In the area of the lateral malleolus the lateral tendon sheath narrowed (in the dog only in the proximal segment). The synovial structures on the plantar aspect in the cat, dog, pig, and sheep were formed by a recess of the tarsometatarsal joint; while in the ox and goat they formed a tendon sheath that took its origin from the same joint. The plantar recess surrounded the tendon three quarters of the way in the dog, and in cat, pig, and sheep only half way. Nomenclaturial consequences for the NAV are discussed. PMID- 2240589 TI - Fine structure of the feline tapetum lucidum. AB - The morphology of the tapetum lucidum of the domestic cat (Felis catus) was studied by electron microscopy. The tapetum is a tapetum cellulosum, localized in the choroid of the dorsal fundus. The cells comprising this structure are described. PMID- 2240590 TI - Hyperplastic and hypertrophic growth of lateral muscle in Dicentrarchus labrax (L.). An ultrastructural and morphometric study. AB - In this EM study of lateral muscle in Dicentrarchus labrax, we observed that during the larval period, growth of the presumptive red and white muscle layers occurs both by hypertrophy (as fibres already present at hatching complete their maturation) and by production of new fibres in germinal zones specific to the two muscle layers. In the first half of larval life the presumptive white muscle increases in thickness by the addition, superficially, of new fibres derived from a germinal zone of presumptive myoblasts lying beneath the red muscle layer. In the second half of larval life new fibres produced in this same zone form the intermediate (or pink) muscle layer. Dorsoventrally the myotome grows throughout larval life, largely by addition of new fibres from germinal zones at the hypo- and epi-axial extremities. Towards the end of larval life all these germinal zones are becoming exhausted, but another source of fibres arises as satellite cells, associated with large-diameter presumptive white muscle fibres, are activated to produce new fibres. The addition of small, new fibres gives the white muscle its mosaic appearance. Morphometric analysis of fibre diameters in the white muscle confirms that whereas these hyperplastic processes are important during the larval and juvenile periods, when growth is very rapid, they have ceased by the time the adult stage is attained. By contrast, fibre hypertrophy continues through into adult life. The presumptive red muscle consists initially of a monolayer of fibres present only near the lateral line, and during larval life it grows hypo- and epi-axially by addition of fibres derived from myoblasts already present in these areas at hatching. Lying superficially to the presumptive red muscle monolayer there is a near-continuous layer of external cells with a "flattened" profile. During the second half of larval life, differentiation of these external cells into myoblasts provides the source of new fibres which are added to the red muscle layer. This process, which occurs initially in the region around the lateral line and later spreads outwards, is responsible for the increase in thickness of the red muscle. PMID- 2240591 TI - Mode of neuronal migration of the pontine stream in fetal mice. AB - The migration of immature neurons in the pontomedullary subpial region was examined in fetal mice by light and electron microscopy. Immature pontine cells were observed forming a cell strand from the ventral aspect of the fourth ventricle to the pontine flexure during the period between the 14th and 17th day of gestation. These cells were elongated and oriented parallel to the direction of migration, and displayed features of immature neurons: they contained a high concentration of ribosomal rosettes and a few cisternae of rough endoplasmic reticula, as well as Golgi apparatus, mitochondria, microtubules and centrioles. Many of the neurons extended leading processes, and these contained longitudinally-arrayed microtubules. Filopodia extending from the processes were found beneath the pia mater. Relocating cells displayed contact relationships between themselves; in the caudal part of the stream, translocating neurons were apposed to each other and fibers of various diameters, and in the rostral area of the stream, many fibers were noted, and corresponded to leading processes of relocating neurons, to which other cell bodies had close contact. From the arrangement of the immature neurons and their processes, it can be inferred that developing fibers act as guidance substrates for the translocation of embryonic pontine neurons. PMID- 2240592 TI - Synaptic junctions between sympathetic axon terminals and pinealocytes in the monkey Macaca fascicularis. AB - The distribution of axon terminals in the pineal gland of monkeys was studied by electron microscopy. Numerous terminals bearing small pleomorphic agranular and dense-cored vesicles were localized in the perivascular space and among the pinealocytes in the parenchyma in normal monkeys. Following bilateral superior cervical ganglionectomy, they underwent degenerative changes, including the accumulation of glycogen masses, appearance of dense residual bodies and the displacement of synaptic vesicles. Some of these degenerating terminals showed synaptic contacts with the cell bodies of pinealocytes. At the synaptic junction the postsynaptic membrane was thickened asymmetrically. Examples of synaptic contacts were most frequently observed in 5 and 7 days postoperative animals. In the longer surviving (30 days) monkey, most of the axon terminals showed round agranular vesicles, and they were mainly presynaptic to the intrapineal ganglion cells with some of the pinealocytes. They remained structurally unchanged following the resection of both the superior cervical ganglia. A few axon terminals containing small dense-cored vesicles appeared to have survived the initial insult, but some of their vesicles appeared swollen 30 days after the operation. It is concluded from this study that some of the pinealocytes are under the influence by the postganglionic neurons in the superior cervical ganglia through direct synaptic contacts. The intrapineal ganglion cells are postsynaptic to fibres originating exclusively from the central nervous system. Some of these fibres, however, may be presynaptic directly to pinealocytes. PMID- 2240593 TI - Pronephric regression during larval life in the sea lamprey, Petromyzon marinus L. A histochemical and ultrastructural study. AB - The regression of the pronephric kidney of the lamprey, Petromyzon marinus, is described using histochemical and ultrastructural techniques. Regression begins in the third year of larval life, and by the time the animal enters metamorphosis the tubules have all disappeared. The nephrostomes and the renal corpuscle, however, persist for the remainder of the life cycle and undergo little change in the larva. Iron is present within the tubular epithelium prior to the beginning of degeneration, but as degeneration proceeds iron is observed within the tubule lumina. Acid phosphatase is noted within the tubule epithelia prior to degeneration, but as degeneration proceeds acid phosphatase is also observed within the intertubular area. Features of tubular regression include a prominent and highly folded basal lamina, numerous cytoplasmic inclusions, and dense bodies in the epithelia and lumina. The intertubular region is invaded by lymphocytes, granulocytes, plasma cells, and macrophages. The process of pronephric regression possesses many features of the process of apoptosis, which has been noted in the regression of larval organs in other vertebrates. PMID- 2240595 TI - On the fine structure of arc-capillaries: true a.v. anastomoses or sphincter capillaries? AB - The arc-capillaries represent vessels of the terminal bed: they are not true arterio-venous anastomoses. They exhibit a typical capillary structure of their wall. The existence of smooth muscle cells and modified smooth muscle cells, such as epithelioid cells, cannot be demonstrated. Likewise, a specific activation by nerves does not exist. The arc-capillaries differ from the net-capillaries neither in the structure of their wall nor in diameter. At the origin of the arc capillaries from the final arteriole there are no smooth muscle cells, only pericytes (adventitial cells). The arc-capillaries branch off where the final arteriole no longer possesses smooth muscle cells. The electron microscopic studies showed that arc-capillaries do not represent sphincter capillaries. PMID- 2240594 TI - Vasoactive intestinal polypeptide (VIP) containing cells in the developing rat occipital hemisphere. AB - Numerous cells were observed to show intense vasoactive intestinal polypeptide (VIP) immunoreactivity from birth to postnatal day 8 in the subventricular zone of the rat occipital hemisphere. This cell population was markedly reduced by postnatal day 8, but isolated clusters of VIP cells persisted into adulthood. In addition, long, L-shaped VIP fibers were seen in the hemispheric wall up to postnatal day 16, but not in the adult. Parallel to the reduction in number of the subventricular VIP cells an increasing number of VIP cells appeared in the neo- and allocortex, developing by postnatal day 12 all the features of the mature cortical bipolar fusiform neurons. As possible alternatives, the migration of subventricular VIP cells into the cortex, the transient character of the subventricular VIP population or the expression of VIP by radial glia are discussed. PMID- 2240596 TI - Body composition and the evolution of the Macropodidae (Potorous, Dendrolagus, and Macropus). AB - The segmental distribution of body weight and the proportions of skin, muscle, and bone are compared for three genera of the Macropodidae (Potorous, Dendrolagus, and Macropus) and one genus of the Petauridae (Pseudocheirus). Potorous and Macropus possess high proportions of muscle mass to total body weight, high concentrations of musculature in the lumbar extensors, thigh, and tail, and disproportionate ratios of forelimb: hindlimb bone and forelimb: hindlimb muscle which correspond to disproportions of intermembral length. These species converge with high-speed terrestrial runners in some traits and remain distinctive in others. Macropus, larger, more muscular, and faster than Potorous, appears to store and return energy to the hopping cycle more efficiently. Dendrolagus has less than three-fourths the musculature of the other macropod genera, low proportions of the back extensor muscles compared to the other macropods, and relatively more equal ratios of forelimb:hindlimb bone and forelimb:hindlimb muscle. This species converges with slow-moving arboreal climbers such as Pseudocheirus. These data on body mass and tissue proportions translate directly into center of gravity, strength-to-weight ratio, and muscular (kinetic) chains, key elements of macropod evolution. The geometric similarity of muscle between smaller potoroids and larger macropodids, and assumption critical to allometric comparison, is not confirmed. PMID- 2240597 TI - Identification of motoneurons in the spinal cord of the zebrafish (Brachydanio rerio), with special reference to motoneurons that innervate intermediate muscle fibers. AB - We investigated the location and size distribution of motoneurons that innervate red, intermediate and white muscle fibers in the axial musculature of the zebrafish (Brachydanio rerio). Motoneurons were identified by retrograde labeling from the respective myotomal compartments with horseradish peroxidase applied either in small polyacrylamide gel fragments or as pure crystals. We found a spatial relationship between the three myotomal muscle fiber types and the corresponding motoneurons. The white motoneurons are grouped in the dorsal part of the motorcolumn, near the central canal. Motoneurons of the red and intermediate muscle are clustered in the ventral part of the motorcolumn. The average position of the red motoneurons is ventral to that of the intermediate motoneurons. Some sizes are distributed over wide overlapping ranges, spanning from 41 to 352 microns 2 for red and intermediate and from 56 to 894 microns 2 for white motoneurons. These data are discussed in relation to the recruitment order of myotomal muscle fibers of different types as revealed by electromyographic recordings in fish, and the so called "size principle" for motoneuron recruitment. PMID- 2240598 TI - Tenotomy-induced motor endplate alterations in rat soleus muscle. AB - The effects of tenotomy on the ultrastructure of rat soleus muscle motor endplates were examined both qualitatively and quantitatively. Rat soleus muscle was studied 2 weeks following tenotomy and compared with normal littermates. The motor endplates from the tenotomized muscles were found to exhibit both degenerative and regenerative changes. Degeneration consisted of postjunctional fold breakdown, exposed junctional folds, myelin-like bodies within the sub junctional sarcoplasm, and dense bodies within the Schwann cell cytoplasm. The regenerative changes consisted of several small nerve terminals occurring within the same primary synaptic cleft and several axons wrapped by the same Schwann cell. The results demonstrate that tenotomy induces denervation-like changes at endplates that lead to terminal sprouting within the neuromuscular junctional area and remodelling. PMID- 2240599 TI - Comparison of mesenteric with antimesenteric crypt and villus populations in the mouse jejunal epithelium. AB - Variation in the size and composition of crypts and villi along the length of the intestinal tract is well known. Here we investigate possible variation around the circumference of the intestine. This is a concern because most studies have ignored potential circumferential variation and its implications for experimental design in cell kinetic studies. We compared the crypt and villus populations of the mesenteric half with those of the antimesenteric half of proximal mouse jejunum. The branching crypt index and crypt and villus dimensions were measured. We found no evidence of differences in the branching crypt index, in the mean crypt and villus size, nor in the distribution of crypt and villus sizes between these two populations. PMID- 2240600 TI - A novel mechanism of capillary growth in the rat pulmonary microcirculation. AB - Postnatally, the rat lung parenchyma undergoes impressive growth. Within four months of birth, lung volume and alveolar and capillary surface areas increase over 20-fold and capillary volume 35-fold. Investigation of methacrylate casts of the pulmonary microvasculature revealed that, with age, lung capillaries were not only growing in surface and volume but also increasing their network density. We proposed that the capillary bed grows by formation of slender intravascular tissue pillars and termed this type of growth intussusceptive microvascular growth (Caduff et al., Anat. Rec., 216:154-164, 1986). The aim of this investigation was to detect the presence and to analyze the ultrastructure of slender tissue posts (diameter 1-2.5 microns) extending across the capillary lumina in serial electron microscopic sections of rat lung parenchyma (age 44 days). Computer-assisted three-dimensional reconstruction of the capillary lumen confirmed that tissue posts were matching the holes previously observed in casts. Post ultrastructure varied with size from a simple area of interendothelial contact to tissue pillars with a core of interstitial tissue. Based on the changing morphology of the pillars, a hypothesis for their development can be proposed: phase I, creation of a zone of contact between opposite capillary walls (formation of an interendothelial bridge); phase II, reorganization of the intercellular junctions of the endothelium, with central perforation of the capillary layer; phase III, formation of an interstitial post core, with successive invasion by cytoplasmic extensions of myofibroblasts, pericytes, and finally interstitial fibers; and phase IV, growth of the slender pillar to a normal full size capillary mesh. These findings support the new concept of intussusceptive growth of the lung capillary system. PMID- 2240601 TI - Immunofluorescent studies for alpha-actinin in cultured cardiomyopathic hamster heart cells. AB - Primary cultures of cardiac myocytes from normal and genetically cardiomyopathic (CM) newborn hamsters (strain UM X7.1) were analyzed by indirect immunofluorescent microscopy after 3, 5, 7, and 9 days in culture. The cultures were fixed in cold acetone and immunostained by an indirect method using FITC labelled anti-alpha-actinin to label the myofibrillar Z bands. Most normal and CM myocytes appeared round in shape after 3 days in culture. Normal cardiac myocytes began to exhibit cytoplasmic projections after 5 days in culture and their myofibrils usually showed parallel arrangements with respect to each other. The cardiac cells from CM hearts showed an obvious myofibril disarray. Moreover, projections formed later than normal. As the size of the cells increased, more and more projections formed in normal hamster myocytes during development. By contrast, most of the cardiomyopathic myocytes showed few projections even as late as 9 days in culture. Hence, the number of projections per cell was much less in cardiomyopathic myocytes than in normal, especially after 7 and 9 days in culture. These results suggest that cardiomyopathic cells have abnormal shapes in culture and, in particular, fail to form projections as in normal cells. Whether this unusual behavior is related to an abnormality of the membranes or cytoskeletal system in cardiomyopathic heart cells or to some other factor requires further study. PMID- 2240603 TI - Pericyte of a teleost fish: ultrastructure, position, and role in neoplasia as revealed by a fish model. AB - The morphology and position of the pericyte, a periendothelial cell, is described for a teleost fish, Cyprinodon variegatus. This cell was found attached to the abluminal surfaces of capillaries, venules, and arterioles of the submucosa of the midgut of the fish. The cell was encompassed by a thin basal lamina, possessed numerous plasmalemmal vesicles, a "sole region" which contained thinner actin-like filaments and possibly thicker myosin-like filaments, and ranged in form from ovoid to stellate, with long cytoplasmic extensions that partially covered the endothelium of the associated microvessel. The pericyte of C. variegatus has been shown to give rise to hemangiopericytomas (experimentally induced with diethylnitrosamine) and possibly to pericytomas. The range of phenotypic expression of these pericyte-derived neoplasms is broad, and dependent upon the degree of differentiation of their constituent cells which range from clear cell pericytes to myofilamentous laden cells that resemble smooth muscle cells. In this regard and in regard to its normal ultrastructural morphology, and anatomical position, in relationship to microvasculature in this fish, the cell is very similar to other vertebrate pericytes. Limited evidence suggests that small fish species may be excellent study models for further elucidation of pericyte form, function, and role in disease. PMID- 2240602 TI - Influence of epithelial-mesenchymal interaction on the viability of facial mesenchyme. II: Synthesis of basement-membrane components during tissue recombination. AB - The presence of basement-membrane components during tissue separation procedures was determined employing monoclonal antibodies to laminin and type IV collagen. In addition, the reconstitution of basement-membrane components and the formation of the basement-membrane were examined in isolated epithelium and mesenchyme and in tissue recombination. Epithelium and mesenchyme of maxillary processes of chick embryos were separated by a variety of protocols, including those employed in a prior study (Saber et al: Anat. Rec. 225:56-66, 1989). Results indicated that the protocol previously employed did not remove basement-membrane components after enzymatic tissue separation. A revised protocol in which the basement membrane components (i.e., laminin and type IV collagen) were removed from isolated tissues prior to recombination revealed that a developmental compartment and a gradient of cell viability, comparable in size and dimensions to that observed in the study of Saber et al. (ibid.) was present in the mesenchyme of recombined explants. Type IV collagen and laminin, therefore, do not appear to be required initially during tissue recombination in order for subsequent growth sustaining effects to be expressed. Additional studies revealed, however, that synthesis of basement-membrane components occurred not only in isolated tissues but was altered markedly by tissue recombination. Culture of isolated tissues demonstrated induction of laminin synthesis in separated epithelium by 24 hours and induction of collagen synthesis in isolated mesenchyme by 24 hours. Recombination of epithelium and mesenchyme, however, resulted in rapid induction of laminin synthesis within 1 hour. Recombination of epithelium and mesenchyme after 24 hours resulted in the presence of laminin not only in epithelium but in mesenchyme as well. Both tissues were required for basement-membrane formation which appeared to be fully reconstituted by 24 hours in culture. These observations indicate that recombination in culture alters the pattern of synthetic activity of these basement-membrane components. These can be characterized as "early" (temporal) and "late" spatial) responses by the recombined tissues. PMID- 2240604 TI - Developmental appearance and ultrastructural immunolocalization of a major 66 kDa phosphoprotein in embryonic and post-natal chicken bone. AB - Biochemical analyses and immunocytochemistry were used to examine the developmental appearance of a major approximately 66 kDa bone phosphoprotein (66 kDa BPP) in the mid-diaphyseal region of embryonic and post-natal chicken tibiae in vivo. Total protein and O-phosphoserine (Ser-P) and O-phosphothreonine (Thr-P) content of 8-, 12-, and 18-day embryonic, and 4-wk post-natal chicken tibiae were determined by amino acid analysis. Similar bone samples were carried through a wide variety of tissue-processing regimes including different protocols for fixation, decalcification, dehydration, and embedding prior to electron microscopy. For immunocytochemistry, tissue sections were incubated with a polyclonal antibody raised in rabbits against 66 kDa BPP, and the antigen was revealed by the high-resolution protein A-gold technique. Amino acid analysis, Western blotting, and immunocytochemistry all showed the presence and increasing concentration of bone phosphoprotein with advancing developmental age. Immunogold labeling was observed over osteoblasts and mineral deposits throughout the bone with the most intense reaction occurring at the mineralization front in embryonic tibiae. Electron probe X-ray microanalysis confirmed the association of 66 kDa BPP with mineral. The levels of phosphoprotein in the tissue were directly correlated with increasing degrees of mineralization. These observations are consistent with previous proposals suggesting that phosphoproteins may play a significant role in the calcification of bone matrix. PMID- 2240605 TI - Expression and ultrastructural immunolocalization of a major 66 kDa phosphoprotein synthesized by chicken osteoblasts during mineralization in vitro. AB - Embryonic chicken osteoblasts cultured over a 30 day period were used as a model system for studying the expression of bone phosphoproteins during cellular differentiation and the possible role of these proteins in extracellular matrix mineralization. Accumulation of total phosphoprotein in the cultures, as determined by O-phosphoserine (Ser-P) and O-phosphothreonine (Thr-P) amino acid analysis, revealed a greater than 10-fold increase over the 30 day period. Total phosphoprotein synthesis, as assessed by (32P)-, (3H)-Ser-P, and (14C)-Thr-P protein labeling, showed the highest levels concurrent with initial mineral deposition within the matrix. The major phosphoprotein present in chicken bones and synthesized by the cultured osteoblasts had a molecular weight of approximately 66 kDa. This 66 kDa bone phosphoprotein (66 kDa BPP) was purified to homogeneity and was used for antibody production. Application of this antibody in Western blot analysis revealed that 66 kDa BPP was present only in protein extracts of mineralizing cultured osteoblasts and was absent in cultures of non mineralizing chondrocytes, myoblasts, and tendon fibroblasts. The 66 kDa BPP in vitro accumulated continuously in the extracellular matrix in a manner that paralleled both phosphoprotein synthesis and total phospho-amino acid production. A comparison of the results obtained in vitro to those from developing embryonic tibiae in vivo demonstrated a similar qualitative and temporal expression of phosphoprotein and a continual accumulation of 66 kDa BPP in the matrix with advancing mineralization and developmental age. Ultrastructural immunocytochemistry using the 66 kDa BPP antibody and the protein A-gold technique revealed specific immunolabeling over electron-dense regions of mineralization in the cultures that appeared identical to the distribution of labeling observed in vivo (McKee et al.: Connect. Tissue Res., 21:21-29, 1989; Anat. Rec., 228:77-92, 1990). These results demonstrate that this major 66 kDa BPP was expressed concurrently with other differentiated osteoblast functions and suggests that it may play a role in the initiation or regulation of mineralization. PMID- 2240606 TI - Histochemical, ultrastructural, and electron microprobe analytical studies on the localization of calcium in rat incisor ameloblasts at early stage amelogenesis. AB - The enamel organs of rat incisors were separated from the enamel surface and processed for rapid freezing and freeze-substitution. A histochemical stain for calcium (GBHA) of thick Epon sections revealed intense calcium reactions in the secretory ameloblasts, exclusively in the tubulovesicular structures extending throughout their distal cytoplasm. Electron microscopy revealed a thin layer of amorphous material with clusters of electron-dense granules along the distal surface of secretory ameloblasts. In young secretory ameloblasts without typical Tomes' processes, a considerable number of mitochondria were located in the distal cytoplasm and contained numerous electron-dense granules. Similar dense granules as well as fine ribbon-like electron-dense figures, all containing significant amounts of calcium, were observed in some of the tubulovesicular structures at the distal end of these cells. A putative exocytotic figure of such dense granules was also observed. The electron-dense granules were rare in more differentiated ameloblasts with elongated Tomes' processes, which occasionally displayed ribbon-like figures in some of the tubulovesicular structures in the process region. No significant calcium peak was detected in the extracellular amorphous material, secretory granules, or along the lateral plasma membranes. These observations may imply high calcium concentrations in mitochondria and tubulovesicular structures in the distal cytoplasm of secretory ameloblasts relative to that of the cytosol and support the possible contribution of these organelles in secretory ameloblasts to cellular calcium regulation at least in the early stage of amelogenesis. PMID- 2240607 TI - Evidence that apatite crystals of rat incisor enamel have hexagonal cross sections. AB - Images of nearly cross sectioned enamel crystals obtained with the transmission electron microscope were examined in detail and correlated with various possible cross-sectional shapes of the crystals. The following images were seen: 1) elongated hexagons with sharp outlines, maximal density, and minimal size (type A profile); 2) elongated hexagons with one pair of long sides of high contrast, two pairs of short sides of low contrast, high density in the center of the image, and low density towards the low contrast sides (type B profile); 3) slanted hexagons with one pair of high contrast sides, two pairs of low contrast sides (one pair of long, one pair of short sides), and the density decreasing from the center towards the low contrast sides (type C profile); this profile was seen more frequently than the type B profile; and 4) octagons with low contrast edges all around, the density decreasing from the center towards the edges (type D profile). Types B, C, and D profiles were larger than type A profiles. Similar crystal images have been described in the literature. When tilting a specimen in increments of 6 degrees, the transformation of type A to type C and type C to type D profiles was observed. Many crystal images did not change their shape greatly when tilting the section through 6 degrees. No rectangular or rhomboidal profiles were seen. It is argued that types A, B, C, and D profiles cannot be generated by apatite crystals with a parallelepiped cross section. They are easily explained, however, on the basis of crystals with hexagonal cross section. PMID- 2240608 TI - A scanning electron microscopy morphometric study of the rabbit peritoneal surface. AB - Rabbit peritoneum was studied by SEM to obtain information and statistically meaningful morphometric data of different sites of visceral and parietal peritoneum and to verify the existence of "stomata." Samples were fixed by intraperitoneal infusion of glutaraldehyde, and were photographed by SEM under standard conditions. Morphometric data were obtained by Kontron MOP Videoplan. Variable cell surface patterns were present even within limited areas; however, "stomata" were not observed. The heterogeneity of data obtained can be related to the dynamism of mesothelial cell activity and to the different motilities of the underlying organs. PMID- 2240609 TI - Spatial distribution of "tissue-specific" antigens in the developing human heart and skeletal muscle. I. An immunohistochemical analysis of creatine kinase isoenzyme expression patterns. AB - Using monoclonal antibodies against the M and B subunit isoforms of creatine kinase (CK) we have investigated their distribution in developing human skeletal and cardiac muscle immunohistochemically. It is demonstrated that in skeletal muscle, a switch from CK-B to CK-M takes place around the week 8 of development, whereas in the developing heart, CK-M is the predominant isoform from the earliest stage examined onward (i.e., 4 1/2 weeks of development). In all hearts examined, local differences in concentration of the CK isoforms are observed. The CK-M expression in the developing outflow tract (OFT) and conduction system is described in detail. Between the weeks 5 and 7 of development, the distal portion of the OFT is characterized by low CK-M expression, whereas around the week 8-10 of development the myocardium around the developing semilunar valves in the OFT expresses a very high level of CK-M. At all stages examined, a relatively low CK M level is observed in those regions in which the "slow" components of the conduction system do develop (e.g., the sinoatrial junction and atrioventricular junction), whereas a relatively high concentration of CK-M is observed in those areas that are destined to become the "fast" components, i.e., the subendocardial myocardium of the ventricles. The high expression of CK-M in the developing "fast components" of the conduction system contrasts with the relatively low expression of CK-M in the force-producing myocardium of the interventricular septum and free ventricular wall. PMID- 2240610 TI - Glycoconjugate unique to migrating primordial germ cells differs with genera. AB - Previous cytochemical studies showing that rat primordial germ cells (PGCs) possess a unique surface glycoconjugate containing terminal alpha-N acetylgalactosamine were extended in this study to determine whether a similar distinctive glycoconjugate coats the surface of PGCs in the mouse. The results showed that mouse PGCs fail to react with peroxidase-conjugated lectins specific for localizing glycoconjugate with terminal N-acetylgalactosamine. All available lectin conjugates with affinity for other terminal sugars or internal sugar linkages also failed to stain mouse PGCs except for the conjugates that bind to alpha-fucose. One fucose-specific lectin conjugate stained only PGCs in the early mouse embryo but stained additional sites in more mature embryos and lost reactivity with PGCs after gestational day 14. Another fucose-specific conjugate stained PGCs until day 15, but with less selectivity, and a third such conjugate bound to several sites, but not to PGCs. The results suggest that the developmental mechanisms mediating cellular interaction, migration, and differentiation may be similar in different genera, but the specific structure of the cell surface glycoconjugate involved in these mechanisms differs. PMID- 2240611 TI - Impaired development of the thymic primordium after neural crest ablation. AB - Impaired thymic development as a result of ablation of neural crest has been observed in embryos late in development. The present study was initiated to determine what changes are effected early in thymic development by neural crest ablation. The epithelial primordia of the thymus were studied in chick embryos on the sixth day of incubation. Embryos with neural crest ablations were compared with sham-operated and untreated controls. Neural crest ablation inhibited formation of epithelial thymic primordia. Primordia in experimental embryos were fewer in number and were smaller than in shams and untreated controls. When primordia from shams and controls were transplanted to the chorioallantoic membrane of chick hosts, they were able to develop into organs with the typical features of embryonic thymus. Similar transplantation from neural crest-ablated animals, on the other hand, led to small, predominantly epithelial structures with meager lymphoid development. These findings are consistent with the hypothesis that mesenchyme derived from cranial neural crest is critical in initiating and sustaining the development from pharyngeal pouches of epithelial structures competent to attract and support the proliferation and differentiation of lymphoid stem cells. PMID- 2240612 TI - Myotome and early neurogenesis in chick embryos. AB - The present study was undertaken in order to verify the identification of profiles of presumptive growth cones in vivo. The developing spinal nerves of chick embryos were studied by light and electron microscopy. We traced the onset of efferent and afferent innervation of the myotome in 2- to 4-day-old chick embryos in order to be sure that we were examining the growing tips of axons. In the process of studying these growing axons, we were able to observe some unique relationships of neural tube, myotome, and differentiating spinal nerves. The neural tube tightly abuts the myotome in Hamburger and Hamilton's (HH) stage 14 chick embryos and cytoplasmic projections from the myotome directly abut the neural tube. The first ventral roots could be identified in HH stage 15 embryos and dorsal roots in HH stage 16 embryos, both under 2 1/2 days of age. The advancing spinal nerve courses toward the anterior or cranial half of the myotome, and growth cones directly contact the medial wall of the myotome. The spinal nerves continue to abut tightly the myotome during the succeeding day of embryonic life, and growth cones enter the substance of the myotome by 3 days, or HH stage 19 embryos. These dorsolaterally directed axons will form the dorsal ramus of the spinal nerves and the ventral ramus continues to be contiguous with the myotome. Invasion of the myotome by axons (putative innervation), and thus innervation of myotomal cells in the 3-day chick embryos, was a totally unexpected finding. The myotome and its potential derivatives thus have extensive neural contact by 3 days of embryonic life in the chick. These findings document a parallel differentiation of afferent and efferent elements of the nervous system and confirm previous accounts identifying growth cones in an intact organism. These findings suggest that afferent as well as efferent nerves may have critical roles in the differentiation of the mesodermal as well as ectodermal derivatives. PMID- 2240613 TI - Effects of advancing age on the central response of rat facial neurons to axotomy: light microscope morphometry. AB - Following axotomy, the regrowth of peripheral axons takes longer in older individuals than in young ones. The present study compares central responses of facial motor neurons to a crush injury of the facial nerve in 3-month-old and 15 month-old male rats sampled through 28 days post-crush (dpc). Neuronal somata, nuclei, and nucleoli were measured in 30 microns brain stem sections within subdivisions of the facial nucleus that contain the cell bodies responsible for the movement of the vibrissae. The temporal patterns of change in the size of the three structures were interpreted with reference to the re-establishment of functional connections, i.e., the return of voluntary vibrissae activity, which is delayed by 4 days in the older animals relative to the younger ones. There was no age-related difference in the pattern of somal swelling and recovery, nor was there an age-related difference in the response of nuclei and nucleoli to axotomy through 4 dpc. Both nuclei and nucleoli increased in size in animals of both age groups, but after 4 dpc in the older animals nuclear enlargement was prolonged and the nucleolar increases were less robust compared to the younger animals. The greatest age difference appeared with the re-establishment of functional connections. In the 3-month-old animals, the resumption of whisker activity coincided with vigorous transient increases in the sizes of nuclei and nucleoli; in the 15-month-old animals, there was little nuclear response to functional recovery and a comparatively small increase in nuclear sizes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240615 TI - An HRP study of location of the rabbit palatopharyngeal motoneurons and peripheral course of their axons. AB - The location of the rabbit palatopharyngeal motoneurons and the peripheral course of their axons were investigated with intramuscular injection of HRP either in the normal animal or in conjunction with intracranial severing of the vagal rootlets. Labeled palatopharyngeal motoneurons were ipsilaterally located within a subdivision of the nucleus ambiguus which is formed by a compact arrangement of the smallest neurons of the nucleus and situated in the rostral of the nucleus. We named that subdivision the compact cell group (CoG). The labeled motoneurons occupied the caudal half of the CoG at a level from about 500 to 1,900 microns rostral to the obex. Labeling was completely abolished by severing the vagal rootlets, indicating that the axons of the palatopharyngeal motoneurons traversed the vagal rootlets. PMID- 2240614 TI - Stage-dependent spontaneous frog dorsal root ganglion neuritogenesis on polylysine in vitro. AB - Dorsal root ganglia of larval frog extended elaborate neuritic arrays in vitro under minimal culture conditions in the absence of medium-supplemented stimulatory factors. The highly adhesive attachment substratum polylysine provided the necessary condition for exuberant outgrowth, the extent of which was dependent on the developmental stage of the animal from which the neural tissue was derived, as was the capability for long-term survival. It appears that an appropriate substratum can substitute for added growth factors in eliciting robust and long-lived sensory neurites in vitro. PMID- 2240616 TI - Araldite F as injection material for quantitative morphology of cerebral vascularization. AB - This study deals with the applicability of Araldite F as injection medium for quantitative morphology of the cerebral vascularization. The physical properties of the plastic that are essential for obtaining optimal results have been determined and tested by injection into the cerebral vessels of ten dog brains and five human brains. The dynamic viscosity (at 20 degrees C) of the plastic is 1.5 times that of blood. The polymerization time (+/- 45 min) is long enough to fill the whole vascular tree in a large organ such as the human brain. The plastic shows minimal volume shrinkage (3.90% +/- 0.05%), and the final cast is suitable for scanning electron microscopy (SEM) investigation after corrosion and histological morphometrical examination after embedding in 2-hydroxyethyl methacrylate (GMA). Special attention has been paid to the conditions under which injection of Araldite F into the cerebral arteries must take place to obtain the most accurate quantitative data on cerebral vascularization and vascular area distribution. Simultaneous injection of the major cerebral arteries of fresh autopsy material, after having removed blood clots by perfusing Kabikinase, is recommended. PMID- 2240617 TI - Cortisol and transcortin in human seminal plasma and amniotic fluid as estimated by modern specific assays. AB - Cortisol concentrations in human seminal plasma, as estimated by the very specific Amersham 'Amerlite' luminescence immunoassay, were 176 +/- 43 (85-260) nmol/l, that is, 63.7 +/- 15.5 (31-94) ng/ml (mean +/- SD, n = 21). This is about 60% of random levels in blood serum and is the first description of cortisol in seminal fluid. In human amniotic fluid at 16-22 weeks of gestation, cortisol concentrations were lower, at 72.6 +/- 14.6 (63-124) nmol/l, that is, 29.3 +/- 5.3 (23-45) ng/ml (n = 21). Concentrations were about 15% of random maternal serum levels in the second trimester of pregnancy. The cortisol concentrations in both fluids were considerably higher than those reported for saliva, which has a mean of about 10 nmol/l. Transcortin (corticosteroid binding globulin, CBG), has been found in human seminal plasma and amniotic fluid for the first time. Concentrations were low, with values up to 12 micrograms/ml, with no significant difference between the two fluids, when using the IRE-Megenix monoclonal iodinated radioimmunoassay. Transcortin concentrations were about 10% of levels in non-pregnant blood serum, compared with about 0.1% for saliva. The higher concentrations of transcortin could perhaps account for the greater diffusion of cortisol into seminal plasma and amniotic fluid. The presence of beta-endorphin, ACTH and cortisol in amniotic fluid, seminal fluid, ovarian follicular fluid, endometrial fluid and gastric fluid may possibly, indicate the existence of a small paracrine ACTH-cortisol axis in the relevant secretory tissues. PMID- 2240618 TI - Alpha-glucosidase activity and sperm motility. AB - We correlated the activity of alpha-glucosidase in seminal plasma with the motility and differential motility of sperm. Significant positive correlations were found between the alpha-glucosidase activity and both motility and the percentage sperm with good forward progression. This supports the use of alpha glucosidase in semen as a marker of epididymal function and specifically of the development of motility. PMID- 2240619 TI - Electrophoretic patterns of spermatozoal nucleoproteins (NP) in fertile men and infertility patients and comparison with NP of somatic cells. AB - During spermatogenesis in mammals the evolutionary early histones are replaced step by step by more species specific nucleoproteins (protamines). The protamines protect the genetic information of the male against mutagenic or other damaging influences and possibly play a role in male fertility. A method was presented to study the nucleoproteins (NP) of single human ejaculates. This procedure was checked concerning its usability and validity by bull spermatozoa. The NP of cryopreserved human spermatozoa of fertile men and of infertility patients were investigated and compared with the electrophoretic patterns of NP of somatic hepatocytes of rat and mouse. A total of 48 semen samples were studied. Ten of these samples were obtained from semen donors of proven fertility and 38 samples were collected from male partners of infertile couples. Photodensitometrically it could be distinguished between percentages of non-protamines (PNP) and percentages of protamines (PP). The PP varied intra-individually with a mean standard deviation of 34%, analogously to the alterations of classical semen parameters. The PP of fertile men did not significantly differ from the infertility patients with normal spermiogram parameters but showed a significantly higher value compared with the semen samples with pathological spermiograms. On average the PP of all infertile patients were significantly lower than the PP of fertile semen donors. PMID- 2240620 TI - Separation of sub-populations of sperm with higher fertility potential from normal and pathological semen by peanut agglutinin. AB - Incubation of human sperm from semen with counts below 20 x 10(6)/ml with peanut agglutinin (PNA) resulted in agglutination of about 70% of sperm. An inverse correlation was found between non-agglutinating (PNA) sperm and sperm density (r = 0.48, p less than 0.01) and a direct correlation with acrosome-damaged sperm (r = 0.83, p less than 0.001). Binding of 125I-PNA to sperm revealed high, and possibly also low affinity binding sites on sperm from both normozoospermic and oligozoospermic origins. Quantitative transmission electron microscopy analysis revealed that agglutinated, PNA+, sperm had lower frequency of acrosomeless spermatozoa than PNA(-)-sperm (44% versus 77%) and higher fertility score (+0.18 +/- 0.1 and -1.5 +/- 0.87 respectively, p less than 0.01). Removal of PNA- sperm from oligozoospermic semen may increase the fertility score of the remaining sperm. PMID- 2240621 TI - Catecholamine distribution in adult rat testis. AB - Catecholamine distribution in the adult rat testis was examined using a sensitive radioenzymatic method. Norepinephrine was present in the capsule and the interstitial fluid, in higher concentrations than dopamine, while in the interstitial cell preparations only norepinephrine was found. Epinephrine was undetectable in all testicular compartments investigated. No catecholamines were found in the seminiferous tubules. Testicular denervation caused a significant decrease in capsular catecholamines, confirming the neural origin of these amines. PMID- 2240622 TI - Postcoital test: which form of spermatozoal motility is associated with a good fertility outcome? AB - The objectives of this study were to examine the predictive value of the PCT in relation to treatment-independent conception rates, to determine which cutoff point best predicted fertility outcome, and which form of spermatozoal motility on PCT is most significantly related to fertility outcome. A prospective study was undertaken of couples referred for the investigation of "unexplained" infertility. One hundred and twenty six couples were recruited between July 1984 and April 1986. On further investigation female infertility factors were identified in 32 (25%) of couples, who were therefore excluded from the study. All conceptions were treatment independent. The relationship between the result of the postcoital test and the chance of conception was studied using a modification of Cox's regression model of life table analysis. The mean length of involuntary infertility prior to referral was 75 months (range = 18-192, SD = 39.2). The mean length of follow-up was 18 months (range = 1-34, SD = 8.4). A 98% follow-up rate was achieved. Eighteen women conceived, giving a 32-month treatment-independent conception rate of 22%. A cutoff point of one spermatozoon exhibiting sluggish motility per HPF was the most effective method of classifying the results of the postcoital test (X2(1) = 4.28, P = 0.037, RR = 4.7. This would suggest that the most efficient form of spermatozoal motion in cervical mucus is slow or sluggish motility. PMID- 2240623 TI - Semen parameters and conception rates after surgical treatment and sclerotherapy of varicocele. AB - Varicocele is an important cause of male subfertility which may lead to varying degrees of pathological semen quality. Removal of varicocele can be an effective andrological treatment if associated with subfertility. Therefore, in a retrospective study, two possible methods of treatment, high ligation and transcatheter sclerotherapy, were compared with regard to semen parameters and conception rates. Three months after treatment, only high ligation showed a significant improvement of sperm concentration, morphology and motility. Sperm concentration and motility, however, similarly increased in both groups after six to nine months. Sclerotherapy showed a better conception rate of 25% than the surgical group with 14%. Sclerotherapy should be the treatment of first choice if associated with subfertility. PMID- 2240624 TI - Zinc levels in seminal plasma of fertile and infertile men. AB - Zinc levels were measured in seminal plasma from 78 men classified on the basis of spermogram analyses into five groups: normo-, oligo-, astheno-, oligoastheno- and azoospermia. Higher zinc levels were found in seminal plasma from the group of asthenozoospermia men in comparison to normo-, oligoastheno- (p less than 0.001), oligo- and azoospermia men (p less than 0.01), while no significant differences appeared when other group pairs were compared. Seminal plasma zinc levels were positively correlated with sperm density (r = 0.6358, p less than 0.01) in asthenozoospermia men, whereas a significant negative correlation was seen in all groups between percentage forms showing normal progressive motility and zinc concentration in seminal plasma. Although zinc is required in seminal plasma for normal spermatozoon functionality, excessively high levels of this ion may be related with defective motility in asthenozoospermia samples. PMID- 2240625 TI - Cytogenetical and histopathologic study of two cases of polled goats. AB - Two young intersexed polled goats, with ambiguous outside male genital apparatus and marked hypospadias, were studied at cytogenetical and anatomo histopathological level. One subject presented a female karyotype (60,XX) whilst the other had a 60,XX/60,XY chimerism, with 5% of 60,XY lymphocytes. The anatomo histopathologic study of the chimeric subject revealed very small testicles, epididymis ecstasy and atrophic part in the testicular parenchyma. PMID- 2240626 TI - Spermicidal activity of menfegol-coated condom. AB - The spermicidal activity of menfegol-coated condoms was investigated. Menfegol (P menthanyl-phenyl-polyxyethylene [8,8] ether) showed strong spermicidal activity at 0.5 mg/ml and higher concentrations. Semen was ejaculated directly into menfegol-coated condoms (20 mg/condom) or uncoated condoms. Immediately after ejaculation, sperm motility and viability were examined. In the menfegol-coated condoms, sperm motility was completely suppressed and no viable sperm were observed. In the uncoated condoms, most of the sperm were alive, although their motility was almost suppressed. These results indicate that the menfegol-coated condom represents a new birth control method in which the contraceptive efficacy of the condom is enhanced by the spermicidal activity of menfegol. PMID- 2240627 TI - Clinical pharmacology of nitrous oxide: an argument for its continued use. AB - We tested the hypothesis that the administration of nitrous oxide (N2O) causes major (e.g., myocardial infarction, neuronal injury, hypoxemia, infection, death) or minor (e.g., nausea, vomiting, headache, earache) untoward effects in patients requiring anesthesia for 1.5-4 h. Given the higher morbidity and mortality associated with aging, we also tested whether aging increased any untoward effect of N2O. Finally, we investigated whether the substitution of N2O for a fraction of the anesthesia supplied by isoflurane altered the latter's pharmacologic effects. We studied 270 patients scheduled for elective total hip arthroplasty (n = 100), carotid endarterectomy (n = 70), or transsphenoidal hypophysectomy (n = 100) who were randomly assigned within each surgical group to receive isoflurane with or without 60% N2O. Regardless of patient age, we found no difference in major or minor untoward outcomes between anesthetic groups, nor a trend to suggest that a larger data cohort would reveal a significant adverse effect of N2O. The addition of N2O administration decreased the isoflurane requirement for clinical anesthesia but did not alter most of the clinical variables measured in practice, including blood pressure, heart rate, rate of recovery from anesthesia, development of postoperative pain, patient satisfaction with anesthesia, or duration of anesthesia or of hospitalization. Patients given N2O were no more likely to dream during anesthesia, remember events during anesthesia, or be frightened by those events. Our results support the continued use of N2O to anesthetize patients for elective surgery. PMID- 2240628 TI - Effect on outcome of prolonged exposure of patients to nitrous oxide. AB - Prolonged (several days or repeated) exposure to nitrous oxide (N2O) can cause injury or death. To assess whether relatively prolonged anesthesia with N2O in normal patients might similarly cause untoward effects, we investigated whether the addition of N2O to isoflurane anesthesia caused injury to patients having surgical resection of acoustic neuroma lasting approximately 10 h. Twenty-six patients undergoing surgical resection of acoustic neuroma were randomly assigned to a regimen that included or excluded N2O (50%-60%) during isoflurane anesthesia plus intravenous adjuvants. On average, slightly less isoflurane (0.24%) was used during anesthesia with N2O. We measured standard clinical variables (blood pressure, heart rate), oxygen saturation, neurologic status, pain, and the incidence and type of morbid outcomes. Exposure to N2O did not increase the incidence of morbid outcomes (including hepatic injury, infection, or hypoxemia), prolong hospitalization, or increase common postoperative complaints such as nausea, vomiting, coughing, or headache. Patients anesthetized with either regimen were equally satisfied with their anesthetic. PMID- 2240629 TI - No finding of increased myocardial ischemia during or after carotid endarterectomy under anesthesia with nitrous oxide. AB - Nitrous oxide (N2O) has been implicated as a cause of myocardial ischemia. We investigated whether substitution of N2O for a portion of the anesthesia supplied by isoflurane increased myocardial ischemia in patients at risk for such ischemia. Seventy patients having carotid endarterectomies (63 patients) or other carotid surgery (seven patients) were prospectively, randomly assigned to an anesthetic regimen that included or excluded N2O. All other aspects of anesthetic management were similar, except for greater concentrations of oxygen and isoflurane in patients not given N2O. Perioperative monitoring for myocardial ischemia and infarction included 12- or 5-lead electrocardiography, transesophageal echocardiography, and creatine kinase isoenzyme levels. By transesophageal echocardiographic or electrocardiographic criteria, 44% of patients given oxygen but only 21% of those given N2O had myocardial ischemia intraoperatively (P = 0.065). Similarly, myocardial infarction, identified by changes in creatine kinase isoenzymes, occurred in only one patient given N2O but in three given oxygen (not significantly different). Thus we found no trend indicating a greater incidence of myocardial ischemia or infarction associated with the use of N2O. PMID- 2240630 TI - Postoperative hypoxemia after nonabdominal surgery: a frequent event not caused by nitrous oxide. AB - We tested whether anesthesia that includes nitrous oxide (N2O) results in the development of intraoperative and postoperative pulmonary complications, including hypoxemia. We also tested whether aging contributes to the development of such complications, particularly when anesthesia includes N2O. We randomly allocated patients having total hip replacements, carotid endarterectomies, or transsphenoidal hypophysectomies (total n = 270) to an anesthetic regimen with and without N2O (stratified within surgical group). A heat-and-moisture exchanger was included in the anesthetic circuit of all patients. Patients were monitored perioperatively and for 1 wk after surgery using intermittent and continuous pulse oximetry to determine oxyhemoglobin saturation. Intraoperatively, mean oxygen (O2) saturations were lower in patients given N2O, particularly older patients. Hypoxemia (O2 saturation less than 86%) developed in five patients receiving N2O and in one receiving O2. This difference was not significant. Administration of N2O did not decrease postoperative O2 saturation, nor did it alter the incidence of postoperative hypoxemia, cough, or sputum production. PMID- 2240631 TI - Nitrous oxide and epinephrine-induced arrhythmias. AB - We asked whether the sympathomimetic effect of nitrous oxide (N2O) predisposed patients receiving N2O to arrhythmias in response to epinephrine administration. We also asked whether aging contributed to the development of arrhythmias, with or without N2O. One hundred patients having transsphenoidal hypophysectomy were randomly assigned to receive anesthesia including (n = 49) or excluding (n = 51) N2O. All patients were given an injection of epinephrine 1:200,000, with 0.5% lidocaine to produce hemostasis. Using intermittent 12-lead and continuous lead II electrocardiography, we determined the incidence of premature ventricular contraction, isorhythmic atrioventricular (AV) dissociation, and changes in T wave morphology. Patients given N2O had a significantly higher incidence of isorhythmic AV dissociation (61.2% vs 41.2%). A trend toward a higher incidence of multiple premature ventricular contractions (16.3% vs 7.8%) was not statistically significant. Both anesthetic groups had a high incidence of postoperative changes in T-wave morphology (46.9% in the N2O group vs 50.9% in the group not given N2O). Aging alone did not affect the incidence of ventricular ectopic beats, isorhythmic AV dissociation, or changes in electrocardiographic morphology, but correlated with the development of ventricular ectopy during N2O anesthesia. We conclude that the use of N2O correlated with a higher incidence of isorhythmic AV dissociation in response to injection of epinephrine with lidocaine. PMID- 2240632 TI - Nitrous oxide does not impair hepatic function in young or old surgical patients. AB - We investigated whether anesthesia including nitrous oxide (N2O) caused hepatic injury, and whether any adverse effect of N2O was affected by patient age. One hundred patients having total hip replacements were randomly assigned to a regimen that included or excluded N2O (50%-60%) during regional anesthesia supplemented with isoflurane and intravenous adjuvants. Using postoperative plasma levels of alanine aminotransferase, bilirubin, and alkaline phosphatase 1 and 3 days after surgery as indicators of hepatic impairment, we found no evidence that N2O causes hepatic injury in either young or old patients. PMID- 2240633 TI - Effect of nitrous oxide on folate and vitamin B12 metabolism in patients. AB - Exposure to nitrous oxide (N2O) markedly enhances excretion of formic acid and formiminoglutamic acid (FIGLU) in the urine of rats, suggesting a disruption in the normal pathways of folic acid metabolism secondary to an N2O-induced inactivation of methionine synthase. We tested whether surgical patients (23 having total hip replacements and 26 having resection of acoustic neuromas) exposed to isoflurane alone or combined with N2O responded similarly. We found no increase in urinary formic acid and FIGLU in patients exposed to N2O for hip replacement, but a small, transient increase in the FIGLU-to-creatinine ratio in those undergoing resection of acoustic neuromas (mean duration of anesthesia = 9.3 h). This increase peaked at the end of anesthetic exposure and returned toward control levels by the first day after anesthesia and surgery. Low preoperative levels of red blood cell folate and low-normal levels of serum vitamin B12 did not predict an increase in formic acid or FIGLU in response to N2O. Although an occasional patient may prove highly susceptible to and develop signs of severe vitamin B12 and folic acid deficiency after exposure to N2O, our findings suggest that this is a rare event. PMID- 2240634 TI - Hematologic effects of nitrous oxide in surgical patients. AB - Nitrous oxide can cause hematologic abnormalities, including death, if it is administered for several days. However, the adverse hematologic effects of its use for surgical anesthesia are unclear. Accordingly, we have studied the hematologic responses of patients undergoing procedures involving hematologic stress or prolonged anesthesia with and without nitrous oxide. We measured red cell count, hemoglobin concentration, mean red cell volume, reticulocyte count, platelet count, mean platelet volume, blood leukocyte level, and leukocyte differential in patients undergoing total hip arthroplasty or removal of an acoustic neuroma. Nitrous oxide did not affect the production of red blood cells or platelets. Nitrous oxide treatment was associated with an increase in postoperative leukocyte levels that was modestly but significantly smaller than that found in patients not given nitrous oxide. There was no evidence that this small decrease in maximal leukocytosis adversely affected clinical outcome. PMID- 2240635 TI - Thoracic epidural anesthesia improves global and regional left ventricular function during stress-induced myocardial ischemia in patients with coronary artery disease. AB - The aim of the present investigation was to study the effects of high thoracic epidural anesthesia (TEA), including the cardiac sympathetic segments, on ischemic ST-segment changes and left ventricular global and regional wall motion abnormalities. Ten patients with a two- or three-vessel coronary artery disease, all treated with the beta-adrenergic blocker metoprolol because of severe stable angina pectoris, performed two identical exercise stress tests, the first without TEA (control exercise) and the second with TEA (TEA exercise). Before each stress test, intravenous metoprolol was given to achieve maximal or near maximal beta adrenoceptor blockade. Systolic and diastolic arterial pressures (radial artery cannula), heart rate, and rate-pressure product, as well as global and regional ejection fractions, using equilibrium radionuclide angiography in the left anterior oblique projection, were measured at rest and during maximal exercise. ST-segment analysis (V3 or V5) was performed, and the regional wall motion score was calculated at control exercise and TEA exercise. Intravenous metoprolol or intravenous metoprolol plus TEA at rest did not cause any significant changes of any of the variables. During TEA exercise, systolic arterial pressure, diastolic arterial pressure, and rate-pressure product, but not heart rate, were significantly lower compared to control exercise. The global and anterolateral ejection fractions were significantly higher (52.8% versus 46.5% and 53.2% versus 46.0%, respectively, P less than 0.05), and the regional wall motion score was significantly lower (8.8 versus 11.8, P less than 0.01) during TEA exercise than during control exercise. ST-segment depression was significantly lower during TEA exercise (-1.03 versus -1.84 mV, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240636 TI - Controlled hypotension with adenosine or sodium nitroprusside during cerebral aneurysm surgery: effects on renal hemodynamics, excretory function, and renin release. AB - Adenosine, a potent vasodilator both in animals and in humans, has been used to produce controlled hypotension in patients, especially during cerebral aneurysm surgery. However, in animals adenosine by intrarenal infusion decreases renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and causes an inhibition of renin secretion. In this study we evaluated the effect of adenosine on RBF in patients (n = 15) scheduled for cerebral aneurysm surgery who had been anesthetized with a modified neurolept-anesthesia during controlled hyperventilation. Perioperative hypotension was achieved with infusion of adenosine (252.8 +/- 55.8 micrograms.kg-1.min-1) (n = 8) or sodium nitroprusside (2.5 +/- 0.8 micrograms.kg-1.min-1) (n = 7). Mean arterial pressure was lowered by 25%-30%, to approximately 60-70 mm Hg, in both groups. Glomerular filtration rate and RBF were measured using standard renal clearance methods for 51Cr ethylenediaminetetraacetic acid and paraaminohippuric acid. Urine and blood samples were collected during normotension before and after a bolus dose of hypertonic mannitol, during hypotension, and during normotension after clipping of the aneurysm. Adenosine induced a marked decrease in GFR (-91%) and RBF ( 92%), and a pronounced increase in renal vascular resistance. Sodium nitroprusside caused a significantly (P less than 0.01) less pronounced decrease in GFR (-24%) and RBF (-36%), but did not affect renal vascular resistance. After discontinuation of the hypotensive agents, GFR returned to baseline levels in both groups. Renal blood flow, however, increased above baseline after discontinuation of adenosine (+93%) but not after sodium nitroprusside. Sodium nitroprusside increased renin secretion, which was not seen with adenosine. Four patients in the adenosine group developed reversible atrioventricular conduction disturbances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240637 TI - Pulmonary hypertension after heparin-protamine: roles of left-sided infusion, histamine, and platelet-activating factor. AB - Severe pulmonary hypertension after protamine neutralization of heparin is an infrequent but life-threatening event following cardiopulmonary bypass. The effect of left ventricular infusion of protamine on pulmonary hypertension as well as a possible role of platelet-activating factor (PAF) or histamine in the heparin-protamine reaction was investigated in 30 pigs in four different groups during general anesthesia. Group 1 animals received 250 IU/kg heparin, followed by 100 mg protamine intravenously after 15 min. In group 2 protamine was infused into the left ventricle. Group 3 animals received the histamine H1- and H2 antagonists clemastine and ranitidine 5 min before protamine infusion. In group 4 the PAF receptor blocker WEB 2086 was given 5 min before protamine. Platelet activating factor was measured by a bioassay in serum samples of group 1 and group 4 animals. In all four groups protamine caused severe pulmonary hypertension, thromboxane A2 release, and a transient decrease in leukocyte counts. No PAF release was detected after protamine infusion. Neither left ventricular infusion of protamine nor histamine or PAF antagonists prevented or attenuated the reactions after protamine infusion. The authors conclude that left ventricular infusion of protamine provides no protection from pulmonary hypertension, and that histamine and PAF are not involved in the acute pulmonary vasoconstriction after protamine neutralization of heparin. PMID- 2240638 TI - Comparison of midazolam and propofol in combination with alfentanil for total intravenous anesthesia. AB - Hemodynamic function during induction of anesthesia, the alfentanil and naloxone requirements, and the speed of recovery from total intravenous anesthesia with alfentanil/midazolam (group M, n = 10) or alfentanil/propofol (group P, n = 10) were compared in patients undergoing lower limb surgery. Twenty patients were randomly assigned to receive either 2 mg/kg propofol in 5 min followed by 9 mg.kg 1.h-1 for 30 min and 4.5 mg.kg-1.h-1 until skin closure, or 0.42 mg/kg midazolam in 5 min followed by 0.125 mg.kg-1.h-1 until skin closure. Simultaneously, a variable-rate infusion of alfentanil was given. Patients were ventilated with 30% oxygen in air. In both groups blood pressure and heart rate decreased significantly (P less than 0.02) and to a similar extent during induction. The total dose of alfentanil was similar in both groups. No patient in group P and nine patients in group M needed naloxone (average dose 130 +/- 70 micrograms, P less than 0.001). Recovery, as judged by psychomotor tests (90% score was reached at 1 h in the P group and at about 4 h in the M group, P less than 0.001), sedative scores, and orientation in time and place, was shorter in group P than in group M. The conclusion is reached that propofol is superior to midazolam in total intravenous anesthesia with alfentanil. PMID- 2240639 TI - Elimination kinetics of sevoflurane and halothane from blood, brain, and adipose tissue in the rat. AB - Using the rat as an animal model, the elimination kinetics of sevoflurane and halothane from brain, blood, and adipose tissue were compared. Elimination of sevoflurane and halothane from blood and brain was biexponential. The rapid, alpha-elimination rates of sevoflurane from blood and brain were faster than the corresponding rates for halothane. However, the slower beta-elimination rates from brain and blood, as well as the elimination rates from adipose tissue, were similar for both volatile anesthetics. Thus, the potential for residual postoperative impairment from subanesthetic tissue concentrations of halothane and sevoflurane may be similar even though sevoflurane is initially eliminated more rapidly from blood and brain. PMID- 2240640 TI - Resistance to atracurium-induced neuromuscular blockade in patients with intractable seizure disorders treated with anticonvulsants. AB - Previous studies have demonstrated that, with the exception of atracurium, resistance to the neuromuscular blocking effects of various muscle relaxants develops in patients receiving anticonvulsant therapy. We studied the effects of 0.5 mg/kg IV atracurium in 53 neurosurgical patients: 21 nonepileptic patients receiving no anticonvulsant therapy (MED = 0); 14 epileptic patients treated with carbamazepine for years (MED = 1); and 18 epileptic patients treated with carbamazepine plus either phenytoin or valproic acid for years (MED = 2). The evoked compound electromyogram of the adductor pollicis brevis was recorded, and results were analyzed using analysis of covariance, with weight and age as covariables. The onset time was not significantly different among the three groups. Times for recovery of baseline and train-of-four responses to stimuli were significantly shorter in the MED = 1 and MED = 2 groups than in control patients (MED = 0). The recovery index (time between 25% and 75% recovery of baseline electromyogram values) was progressively shorter in the three groups (MED = 0: 8.02 min; MED = 1: 5.93 min; MED = 2: 1.96 min; P less than 0.001). This study demonstrates that atracurium, when used on epileptic patients requiring long-term (that is, years of) anticonvulsant therapy, has a shorter duration of action than when used in nonepileptic patients. PMID- 2240641 TI - Lidocaine local anesthesia for arthroscopic knee surgery. AB - Forty-five patients were evaluated during knee arthroscopy performed using local anesthesia produced by lidocaine with epinephrine to determine the dose-response relationship for operative analgesia. Serum lidocaine concentrations were also measured. Patients were randomized prospectively to receive 20 mL of 0.5%, 1.0%, or 1.5% lidocaine with epinephrine intraarticularly. Intraoperative discomfort was measured by verbal response on an 11-point linear pain scale. Pain scores were significantly higher in patients receiving 0.5% lidocaine during the first 45 min of surgery (P = 0.03). After 45 min, pain scores continued to be higher in the 0.5% lidocaine group than in the 1.0% or 1.5% groups, but the differences were not statistically significant. Ninety-four percent of patients in the 1.5% lidocaine group were willing to repeat this anesthetic technique for surgery compared with 83% of those in the 1.0% lidocaine group and 75% of those in the 0.5% lidocaine group (P greater than 0.05). The duration of postoperative analgesia was similar in all groups. Serum lidocaine concentrations before and 15, 30, 60, and 120 min after instillation of lidocaine were highest in the 1.5% lidocaine group with a peak concentration of 278 ng/mL. No patient had symptoms of lidocaine toxicity. We recommend that lidocaine concentrations of 1.0% or 1.5% be used when 20 mL is instilled intraarticularly for knee arthroscopy based on patient comfort and absence of lidocaine toxicity. PMID- 2240642 TI - Fetal heart rate variability after epidural fentanyl during labor. AB - The effects of epidural fentanyl on fetal heart rate (FHR) were examined in 39 parturients, 19 given 75 micrograms epidural fentanyl and 20 given normal saline in 5-mL volumes administered randomly after establishment of adequate epidural lidocaine analgesia. Fetal heart rate was measured 15 min before and 15 min after lidocaine epidural analgesia, and for 60 min at 5-min intervals after administration of epidural fentanyl/placebo. A perinatologist blinded to the injected epidural solution analyzed FHR tracings. Epidural injections of fentanyl and saline, when given during established epidural lidocaine analgesia, were associated with equal reductions in FHR variability and the frequency of FHR accelerations (P less than 0.003). Neonatal outcome was also similar in both groups. The clinical significance, if any, of these moderate reductions in FHR during epidural lidocaine analgesia is unclear. PMID- 2240643 TI - Tracheal insufflation of oxygen at low flow: capabilities and limitations. AB - Tracheal insufflation of oxygen (TRIO) may provide temporary oxygenation for patients or sustain life in apneic mass casualties when conventional ventilatory techniques are not available or feasible. Logistically, minimum flows of TRIO (Vmin) are desirable for field use and to reduce barotrauma should airway obstruction occur. We carried out a feasibility study to determine the efficacy of Vmin of TRIO delivered within 1 cm of the carina, in nine anesthetized and paralyzed dogs. Minimum flows of TRIO for these dogs of average weight (12 kg) was 91 mL/min. In six of the dogs Vmin TRIO was continued and provided oxygenation for an average of 1.5 h compatible with subsequent resuscitation with conventional ventilation. However, PaCO2 levels increased to mean values of 256 mm Hg in the 90 min. To determine what the effect of increased gas mixing was on gas exchange, we repeated Vmin TRIO for 10 min in six of the dogs with and without high frequency oscillations superimposed on the TRIO flow. The oscillations (60 mL at 16.3 Hz) increased carbon dioxide excretion but significantly impaired oxygenation. In completely apneic animals, TRIO at low flow delivered by cricothyroidotomy may be useful as an emergency procedure when upper airway obstruction limits the use of other airway management techniques. However, enhancement of gas mixing during low-flow TRIO impairs oxygenation, so that higher flows would be required when respiratory efforts occur. PMID- 2240644 TI - Emergency tracheal intubation in the postanesthesia care unit: physician error or patient disease? AB - Inadequate airway maintenance has been a major factor in perioperative morbidity. To determine the incidence and etiology of emergency tracheal intubations in the postanesthesia care unit (PACU), we retrospectively reviewed 13,593 consecutive admissions to our PACU from October 1986 through October 1988. Twenty-six patients (26/13,593 = 0.19%) required the insertion of an endotracheal tube while in the PACU. Seventy-seven percent (20/26) of the intubations occurred within 1 h of extubation and/or admission to the PACU. Intubation was more common at the extremes of age; 54% of those intubated were more than 60 yr old (P = 0.003); 19% were less than 3 yr old (P less than 0.05). Twenty-three percent of the intubated patients had undergone otolaryngologic procedures (P = 0.008). Interestingly, 73% of the intubations occurred during the months of January through June (P = 0.016). Median PACU admission scores were lower for the intubated group (P less than 0.001). There was no association between intubation and gender (P = 0.74), anesthetic technique (P = 0.41), or anesthetic agent (P = 0.49). Of the 26 intubations, 18 (69%) were considered to be directly related to anesthetic management. Despite the extremely low incidence of emergency tracheal intubation in a heterogeneous group of patients admitted to our PACU, preventable anesthesia related etiologic factors including excessive sedative or anesthetic effect, inappropriate fluid management, persistent muscle relaxant effect, and upper airway obstruction contributed to the majority of these intubations. PMID- 2240645 TI - Clinical and radiologic evidence of the epidural plica mediana dorsalis. PMID- 2240646 TI - Epileptogenic foci and local cerebral metabolism. PMID- 2240648 TI - Parametric statistics for evaluation of the visual analog scale. PMID- 2240647 TI - An alternative explanation for esophageal perforation during neonatal resuscitation: hazards of nonregulated wall suction. PMID- 2240649 TI - Vasodilator-induced femoral-to-radial pressure gradient after cardiopulmonary bypass. PMID- 2240650 TI - A hazardous defect in a humidifier. PMID- 2240652 TI - A simple chin-support device during face mask anesthesia. PMID- 2240651 TI - Intralipid solution mistakenly infused into epidural space. PMID- 2240653 TI - The evolving legal context for drug testing programs. PMID- 2240654 TI - Measurement of blood cyanide with a microdiffusion method and an ion-specific electrode. AB - The use of a cyanide ion-specific electrode in combination with the Conway microdiffusion method was modified for the measurement of cyanide concentration in human red blood cells and plasma. With our modified method, the optimal pH of cyanide isolation from red blood cells and plasma was investigated. Cyanide recovery from red blood cells increased with decreasing pH. The maximal recovery of 96.9 +/- 2.6% was obtained at a pH of less than 1. Cyanide recovery from plasma, however, peaked at a pH between 7 and 8, and further changes in pH reduced the recovery rate. The maximal recovery rate from plasma was 74.1 +/- 1.5%. In previous studies, cyanide isolations from both plasma and red blood cells were carried out at a pH of less than 1. This study shows that cyanide isolation from plasma should be performed at a pH between 7 and 8. PMID- 2240655 TI - Excessive airway pressure due to ventilator control valve malfunction during anesthesia for open heart surgery. PMID- 2240656 TI - Transvenous pacing for the anesthetic management of surgery for glossopharyngeal neuralgia. PMID- 2240657 TI - Anesthesia for a patient with Kufs' disease. PMID- 2240658 TI - Intramyocardial air causes right ventricular dysfunction after repair of a congenital heart defect. PMID- 2240659 TI - Severe tracheal compression caused by false aneurysm arising from the ascending aorta: successful airway management using induced hypotension and bronchoscopy. PMID- 2240660 TI - Hyperkalemic death during use of a high-capacity fluid warmer for massive transfusion. PMID- 2240661 TI - Making oral midazolam palatable for children. PMID- 2240662 TI - Proper technique for insertion of the laryngeal mask. PMID- 2240663 TI - Anesthesia machine for use during magnetic resonance imaging. PMID- 2240664 TI - Wearing of gloves by anesthesia personnel. PMID- 2240665 TI - Intravenous general anesthesia is not intravenous sedation. PMID- 2240666 TI - Collecting blood for autologous transfusion. PMID- 2240667 TI - Bloodless turbinectomy following blind nasal intubation: faulty technique? PMID- 2240668 TI - Dynamic testing of catheter manometer systems. PMID- 2240669 TI - Transesophageal echocardiography and intraoperative monitoring of left ventricular function. PMID- 2240670 TI - Relationship of regional wall motion abnormalities to hemodynamic indices of myocardial oxygen supply and demand in patients undergoing CABG surgery. AB - To investigate the hemodynamic correlates of perioperative regional wall motion abnormalities (RWMA), we measured wall motion continuously via transesophageal echocardiography (TEE), and related RWMA to continuously measured hemodynamic indices of myocardial oxygen supply and demand (heart rate [HR] and systemic and pulmonary arterial blood pressures). Fifty patients undergoing coronary artery bypass graft (CABG) surgery were studied throughout the prebypass postbypass, and intensive care unit (ICU) periods. Only 28% of TEE episodes (RWMA suggestive of ischemia) were preceded by acute changes in any hemodynamic parameter. Specifically, 7% of TEE episodes were preceded by increases in HR (20% deviation from control), 14% by increases in systolic blood pressure (SBP), 13% by decreases in diastolic blood pressure (DBP), and 9% by increases in pulmonary artery diastolic pressure (PAD). Twelve per cent of TEE episodes were associated with increases in rate-pressure product (RPP) to greater than 12,000, and 27% were associated with decreases in mean arterial pressure (MAP)/HR to less than 1 at the onset of TEE episodes. Comparison among periods revealed that postbypass TEE episodes were more frequently associated with either increases in demand or decreases in supply than were prebypass episodes (53% vs. 25%, P less than 0.05). ECG ischemic episodes also were infrequently (30%) associated with acute changes in HR, SBP, DBP, or PAD. We conclude that perioperative TEE episodes are infrequently triggered by changes in hemodynamics, suggesting that a primary decrease in myocardial oxygen supply may be an important mechanism for most perioperative RWMA. In addition, neither pulmonary artery catheter pressure measurements nor specialized indices (RPP and MAP/HR) appear to be useful in predicting TEE episodes. PMID- 2240671 TI - Electroencephalographic changes during brief cardiac arrest in humans. AB - Slowing and attenuation of the dominant frequency of the electroencephalogram (EEG) are changes commonly used to detect cerebral ischemia. To assess the validity of this method, the EEGs recorded during 93 episodes of circulatory arrest in ten normothermic, lightly anesthetized patients undergoing implantation of automatic internal cardioverting defibrillators (AICDs) were visually inspected for change. The number of events recorded for each patient varied from 5 to 18 and was a function of the duration and success of AICD testing in each patient. In 82 of 93 (88%) episodes, EEG changes were identified, and occurred an average of 10.2 s after the last normal heart beat. Of these 82, 67 (82%) illustrated slowing and attenuation. However, 15 (18%) of the hemodynamic events showed changes not previously described as indicative of cerebral ischemia: 6 (7%) showed a loss of delta-wave activity and 9 (11%) showed an increase in the amplitude of theta activity. Time to onset of these unusual changes (10.6 and 9.2 s, respectively) was not significantly different from that for EEG slowing and attenuation (10.2 s). Five of the ten subjects showed more than one pattern of EEG change. There was no significant difference in the time to onset of EEG change among individual patients, and neither were there differences in patterns of change associated with particular anesthetic agents. These results indicate that in normothermic, lightly anesthetized individuals, cerebral ischemia may cause changes in EEG pattern other than slowing and attenuation of dominant frequencies. These alternative patterns should be recognized as indicative of cerebral ischemia when intraoperative EEG monitoring is performed. PMID- 2240672 TI - Oral midazolam preanesthetic medication in pediatric outpatients. AB - A need exists for a safe and effective oral preanesthetic medication for use in children undergoing elective surgical procedures. We evaluated the effectiveness of three different doses of oral midazolam when administered in combination with atropine prior to ambulatory surgery. In this randomized, double-blind, placebo controlled study, 124 children, ages 1-10 yr, received midazolam, 0.25, 0.50, or 0.75 mg.kg-1 po, and atropine, 0.03 mg.kg-1 po, mixed with apple juice, or a placebo (containing the midazolam vehicle, atropine, and apple juice). A blinded observer noted the child's level of sedation, the quality of separation from parents, and the degree of cooperation with an inhalation induction of anesthesia. Picture-recall was used to assess the amnesic effect of midazolam in children over 5 yr of age. Midazolam 0.75 mg.kg-1 produced significant sedation at 30 min. After procedures lasting an average of 106-113 min, recovery was not prolonged by the oral midazolam-atropine combination. We concluded that oral midazolam 0.5-0.75 mg.kg-1 is an effective preanesthetic medication for pediatric outpatients. PMID- 2240673 TI - Effects of thoracic epidural anesthesia on coronary arteries and arterioles in patients with coronary artery disease. AB - The effect of cardiac sympathetic blockade by high thoracic epidural anesthesia (TEA) (T1-T6, bupivacaine) on the luminal diameter of normal and diseased portions of epicardial coronary arteries was determined by quantitative coronary angiography in patients (n = 27) with severe coronary artery disease (CAD). In a separate group of patients (n = 9) with severe CAD, the effects of TEA on coronary arterioles (resistance vessels) were studied, by measuring total and regional myocardial blood flow and metabolism with the retrograde coronary sinus thermodilution technique. At the stenotic segments, TEA induced an increase in luminal diameter from 1.34 +/- 0.11 to 1.56 +/- 0.13 mm (P less than 0.002), but did not change the diameter of the nonstenotic segments (3.07 +/- 0.13 to 2.99 +/ 0.13 mm). In the second group of patients, TEA induced no changes in coronary perfusion pressure, total or regional myocardial blood flow, coronary venous oxygen content, coronary blood flow distribution, regional myocardial oxygen consumption, or lactate extraction or uptake. Two patients had chest pain in the control situation and had regional myocardial lactate production that was attenuated by TEA. We conclude that TEA may increase the diameter of stenotic epicardial coronary artery segments in patients with CAD without causing a dilation of coronary arterioles. These effects may be beneficial when high TEA is used to treat severe ischemic chest pain in patients at rest. PMID- 2240674 TI - Epidural clonidine analgesia after cesarean section. AB - Epidurally administered clonidine has been reported to produce postoperative analgesia. To assess the efficacy, safety, and appropriate dose of epidural clonidine for post-cesarean section analgesia, we designed a double-blind, placebo-controlled study. Sixty women were randomly assigned to receive epidural administration of saline bolus followed by 24-h saline infusion, 400-micrograms clonidine bolus followed by 10 micrograms/h clonidine infusion, or 800-micrograms clonidine bolus followed by 20 micrograms/h clonidine infusion. Supplemental analgesia was provided with patient-controlled iv morphine. Compared to saline, both clonidine regimens produced analgesia, as measured by verbal pain scores and supplemental iv morphine use during the first 6 h after bolus injection. Time to first morphine use was similar for both clonidine groups and significantly greater than saline. However, compared to saline, only the 20 micrograms/h clonidine infusion resulted in decreased morphine usage over the entire 24-h period. Compared to saline, both clonidine doses decreased blood pressure. This decrease was greater in the 400-micrograms than in the 800-micrograms clonidine group, but no patient required treatment for hypotension. Clonidine decreased heart rate (one patient required atropine for asymptomatic bradycardia) and produced transient sedation. The 800-micrograms clonidine dose prolonged resolution of local anesthetic-induced motor blockade compared to saline. The results suggest that epidurally administered clonidine provides analgesia, as measured by decreased need for supplemental morphine, after cesarean section, but continuous infusion is required for analgesia of more than 6 h duration. PMID- 2240675 TI - Clinical evaluation of clonidine added to lidocaine solution for epidural anesthesia. AB - The effects of clonidine added to lidocaine solution used for epidural anesthesia were assessed in 92 women scheduled for surgery and premedicated with diazepam 10 mg po. Patients received 18 ml 2% lidocaine with clonidine 5 micrograms.ml-1 (group C-5, n = 26), with clonidine 10 micrograms.ml-1 (group C-10, n = 20), with epinephrine 5 micrograms.ml-1 (group E, n = 26), or plain (group P, n = 20). No significant difference in the number of segments of analgesia was found at any observation period among the four groups of patients. The decreases in mean blood pressure (BP) observed 20 min after epidural injection in those given clonidine (5 +/- 8% for C-5, 10 +/- 11% for C-10, mean +/- SD) were similar to those given plain lidocaine (7 +/- 12%) but significantly less than those given epinephrine (18 +/- 12%, P less than 0.01 vs. C-5 or P). The response of BP to ephedrine given for restoring BP during anesthesia was not attenuated in patients who received epidural clonidine. Heart rate (HR) decreased significantly in patients given clonidine 10 micrograms.ml-1 (7 +/- 8%, P less than 0.01), but not in those given clonidine 5 micrograms.ml-1, whereas HR increased significantly in those given lidocaine plain or with epinephrine (10 +/- 8% and 28 +/- 14%, respectively, P less than 0.01). The incidence of sinus bradycardia was similar among the four groups of patients. Significant differences were also observed in sedation score between clonidine groups and groups P or E; sedation appeared approximately 10-20 min after epidural injection in both clonidine groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240676 TI - Exogenous opioids in human breast milk and acute neonatal neurobehavior: a preliminary study. AB - Opioid analgesia requirements, distribution into breast milk, and influence on neonatal neurobehavior were evaluated in ten parturient-neonate pairs nursing after elective cesarean section during epidural anesthesia. Five patients received first a loading dose of intravenous meperidine after umbilical cord clamping, then patient-controlled analgesia (PCA) with intravenous meperidine, and finally meperidine tablets as needed. Five patients received morphine in the same manner. Treatment groups showed no differences with respect to neonatal Apgar scores or visual analog scale (VAS) pain or satisfaction scores at 24 and 48 h postpartum. Breast milk specimens, obtained at 12, 24, 36, 48, 72, and 96 h postpartum and analyzed for opioids and metabolites, showed persistently elevated normeperidine concentrations in the meperidine group. A blinded psychologist evaluated each infant once on the 3rd day of life with the Brazelton Neonatal Behavioral Assessment Scale (NBAS). A priori, the "alertness" and three "human orientation" outcomes of the NBAS were chosen for analysis as best measures of opioid-induced effects. On all four outcomes, neonates in the morphine group scored significantly higher (P less than 0.05) than neonates in the meperidine group. We conclude that post-cesarean delivery PCA with morphine provides equivalent maternal analgesia and overall satisfaction as that provided by PCA with meperidine, but with significantly less neurobehavioral depression among breast-fed neonates on the 3rd day of life. PMID- 2240677 TI - Functional residual capacity in anesthetized children: normal values and values in children with cardiac anomalies. AB - To assess the increase in functional residual capacity (FRC) with growth, FRC was measured after induction of anesthesia in two groups of children. One group consisted of 74 children, 0.1-11.2 yr of age, without signs of cardiorespiratory disease (referred to here as "normal" children), and the other of 21 children, 0.2-6.9 yr of age, with cardiac malformations. Anesthesia was maintained with halothane in the normal children and with fentanyl, droperidol, and nitrous oxide in the children with cardiac anomalies. All patients were paralyzed, their tracheas intubated, and their lungs mechanically ventilated. FRC was measured with an automated tracer gas washout technique. In 70 patients the measurements were performed in duplicate with a mean coefficient of variation of 2.0%. FRC correlated significantly with height, weight, and age in both groups. Multiple regression analysis for both groups considered together indicated no significant improvement when factors for the sex of the child or for the presence of cardiac anomalies were incorporated into the model. In normal children the simple linear and nonlinear regression equations for FRC (in milliliters) versus height (in centimeters) were: FRC = -529 + 9.48 x height, r = 0.96; and FRC = 0.00175 x height2.66, r = 0.97, respectively. The corresponding equations for FRC (in milliliters) versus weight (in kilograms) were: FRC = -92 + 29.9 x weight, r = 0.93; and FRC = 9.51 x weight1.31, r = 0.95.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240678 TI - High thoracic segmental epidural anesthesia diminishes sympathetic outflow to the legs, despite restriction of sensory blockade to the upper thorax. AB - To evaluate whether, after high thoracic segmental epidural anesthesia, sympathetic blockade spreads caudally beyond sensory blockade, we assessed regional skin temperatures by infrared telethermometry in 53 nonpremedicated patients at constant ambient temperature. Either bupivacaine (4.2 ml, 0.75%, n = 10) or an equal volume of saline (placebo, n = 10) was injected at the C7-T2 epidural space in a randomized double-blinded fashion. Results were contrasted to those observed after midthoracic (T6-T9, n = 13) and lumbar (L2-T12, n = 10) epidural injection of an identical dose of bupivacaine or saline (n = 10). Despite restriction of sensory block to the upper thorax with high thoracic epidural anesthesia, skin temperatures increased significantly (P less than 0.05 vs. saline) on the foot (great toe: +1.2 degrees C +/- 2.9 SD; little toe: +0.9 degrees C +/- 2.6) and hand (thumb: +2.0 degrees C +/- 4.0, digit 5: +2.9 degrees C +/- 4.2) but decreased after saline. Midthoracic injection also increased significantly skin temperature on the foot (great toe: +4.0 degrees C +/- 4.9; little toe: +3.6 degrees C +/- 4.8) but not on the hand. In contrast, with lumbar epidural anesthesia, skin temperature increased significantly on the foot (great toe: +8.5 degrees C +/- 2.5; little toe: +8.6 degrees C +/- 2.8) but decreased significantly on the hand (thumb: -3.1 degrees C +/- 2.1; digit 5: -2.8 degrees C +/- 2.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240679 TI - Hypoxemia in the postanesthesia care unit: an observer study. AB - To determine the incidence and duration of hypoxemia in the postanesthesia care unit (PACU), 200 patients were investigated in a single-blind observer study. The number of unrecognized hypoxemic episodes, as well as risk factors and possible association between hypoxemia and postoperative morbidity, were studied. Oxygenation was monitored continuously with a pulse oximeter. One or more hypoxemic episodes (SpO2 less than or equal to 90%) were noted in 55% of the patients. SpO2 values less than or equal to 80% were noted in 13% of the patients. Supplementary oxygen was given during 55% of the 447 hypoxemic episodes registered. The hypoxemic episodes were unrecognized by the staff in 95% of the cases. With stepwise multiple logistic regression analyses, risk factors associated with a higher incidence of hypoxemia were: duration of anesthesia (P less than 0.0001), age (P less than 0.002) and a history of smoking (P less than 0.01). Patients who had undergone regional anesthesia had a lower risk of hypoxemia (P less than 0.0002). The occurrence of hypoxemia in the PACU could not be correlated to postoperative morbidity. We conclude that hypoxemic episodes in our PACU are common and that the routine use of supplemental oxygen combined with normal clinical surveillance did not prevent hypoxemic episodes. PMID- 2240680 TI - Infection during chronic epidural catheterization: diagnosis and treatment. AB - A potentially serious complication of long-term epidural catheterization in cancer patients is infection. The early signs of infection were studied in 350 patients in whom long-term epidural catheters were inserted. Three areas of the catheter track were found to be involved; exit site and superficial catheter track infection, and epidural space infection. The authors identified the early signs of infection in each area and the progress of the infection from the deep track to include the epidural space in four of these patients. All 19 patients who developed deep track or epidural infections were successfully treated with antibiotics and catheter removal. None of the patients required surgery for spinal cord decompression. Catheters were replaced in 15 of the 19 treated patients who requested them after treatment with no recurrent infections. It was concluded that use of long-term epidural catheterization is associated with a definable epidural infection rate. The use of epidural opioid analgesia is an effective and safe means of obtaining pain relief for terminally ill patients when patients are monitored for possible infection and receive prompt treatment when the diagnosis is established. PMID- 2240681 TI - Effects of ketamine on the cardiac papillary muscle of normal hamsters and those with cardiomyopathy. AB - The effect of ketamine (10(-5) and 10(-4) M) on the intrinsic contractility of left ventricular papillary muscle from normal hamsters and those with cardiomyopathy (BIO 82.62, 6-month old) was investigated. At these concentrations, ketamine induced a positive inotropic effect on normal papillary muscle, as shown by an increase in maximum unloaded shortening velocity (+19 +/- 4 and +34 +/- 5%, P less than 0.05), active isometric force (+32 +/- 8 and +57 +/ 11%, P less than 0.05), and peak power output (+40 +/- 8 and +80 +/- 16%, P less than 0.05), and induced a slight decrease in sarcoplasmic reticulum function. Ketamine had no effect on the curvature of the total force-velocity curve, suggesting that it does not modify myothermal economy. Contractility of papillary muscle from hamsters with cardiomyopathy was less than that of controls, as shown by the decrease in isometric active force (-41%, P less than 0.02), peak power output (-33%, P less than 0.05), and sarcoplasmic reticulum function. The positive inotropic effect of ketamine on papillary muscle from hamsters with cardiomyopathy was less marked than in controls and almost suppressed in some cases: only the maximum unloaded shortening velocity was significantly increased with 10(-5) M ketamine (+7 +/- 6%, P less than 0.05), whereas no significant changes were observed in active isometric force (+14 +/- 8 and +13 +/- 11%; nonsignificant [NS]) and peak power output (+9 +/- 5 and +13 +/- 8%; NS) with ketamine (10(-5) and 10(-4) M, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240682 TI - Nitrous oxide effects on isolated myocardium: a reexamination in vitro. AB - This study examined in vitro myocardial depression by 50% N2O. Maximal isometric contractions of guinea pig right ventricular papillary muscles were studied in Tyrode's superfusate at 37 degrees C within a gas-tight chamber. Superfusate (pH at 7.45) and chamber were equilibrated with 95% O2/5% CO2. After control measurements in 95% O2, muscles were studied with 50% N2 and 50% N2O (45% O2/5% CO2) in random order with an intervening and final recovery in oxygen. Muscles were field stimulated after rest and at 0.1-3 Hz. At 37 degrees C, muscle performance deteriorated over time with exposure to reduced oxygen; therefore, identical experiments were performed at 30 degrees C in which no systematic deterioration occurred. Peak tension and maximum rate of tension development (dT/dtmax) were compared for each stimulation rate. At both temperatures, N2O caused a 10-15% depression of contractility as compared to that observed with nitrogen. In a second protocol, muscles were studied at 37 degrees C in 26 mM K+ Tyrode's solution with 0.10 microM isoproterenol to study enhanced contractions mediated by slow (Ca2(+)-channel-dependent) action potentials. Rested-state double stimulations were used (stimulus interval, 250-600 ms) resulting in a first rested-state contraction followed by a second contraction (C2) with rapid initial tension development. The muscles were exposed to nitrogen and N2O as in the force-frequency experiments and did not deteriorate over time. In this setting, N2O also caused a 10-15% depression of C2 contractility as compared with nitrogen. Another set of muscles was studied in 95% O2 to which 0.5% halothane or 1% isoflurane was added before exposure to nitrogen and N2O. The combined depressant action of N2O with either halothane or isoflurane did not differ from that predicted by the simple addition of independent effects; there was no evidence of synergism. Furthermore, N2O (50%) alone depressed dT/dtmax in a manner similar to that of 0.5% halothane and different from that of 1.0% isoflurane. Experiments conducted in iso-osmolar 40 mM Na+ Tyrode's solution, in which activator Ca2+ arose from the sarcoplasmic reticulum Ca2+, also showed greater depression by N2O than nitrogen. N2O (50%) is a myocardial depressant independent of concurrent hypoxic effects with a pattern and magnitude of contractile depression similar to that of 0.5% halothane. PMID- 2240683 TI - Epidural bupivacaine suppresses local glucose utilization in the spinal cord and brain of rats. AB - Using the 2-[14C]deoxyglucose method, the effects of analgesic doses of epidural bupivacaine (300 micrograms) on local spinal cord glucose utilization (SP-LGU) of the cervical, thoracic, and lumbar regions and local cerebral glucose utilization (BR-LGU) in 38 brain structures were examined in conscious rats. In addition, the effects of intramuscular bupivacaine (300 micrograms) and the spinal cord transection (T2) were examined to determine whether the induced metabolic changes, if any, are related to the drug's systemic effect and/or deafferentation. Lumbar epidural bupivacaine sufficient to produce analgesia decreased SP-LGU in the thoracic (18-28%) and lumbar (21-29%) spinal cord but not in the cervical cord. Epidural bupivacaine decreased BR-LGU (15-26%) in 35 of 38 structures examined. With intramuscular bupivacaine, SP-LGU remained unchanged in almost all regions, while BR-LGU was significantly decreased (11-23%) in 23 structures. Plasma concentrations of bupivacaine in the epidural and intramuscular groups were comparable. With spinal cord transection alone, SP-LGU significantly decreased with varying degrees depending on the structure examined, but BR-LGU did not decrease in 36 of 38 structures examined. These results indicate that analgesic doses of epidural bupivacaine decrease SP-LGU, probably reflecting decreased neuronal activity of the spinal cord, and that reduced BR LGU by epidural bupivacaine is most likely due to the drug's systemic effect rather than deafferentation. PMID- 2240684 TI - Differential effect of oncotic pressure on cerebral and extracerebral water content during cardiopulmonary bypass in rabbits. AB - To study the effect of oncotic pressure on brain water content during cardiopulmonary bypass (CPB), 14 anesthetized New Zealand White rabbits underwent 60 min of nonpulsatile CPB at normothermia. Animals were grouped according to the composition of the circuit priming fluid. Group 1 animals (n = 7) received a priming fluid (6.5% hydroxyethyl starch in 0.72 N NaCl; 323 +/- 13 mOsm/kg [mean +/- SD]) that maintained normal colloid oncotic pressure (COP) during CPB (19.0 +/- 1.5 mmHg). Group 2 animals (n = 7) received a priming fluid (0.9 N NaCl; 324 +/- 23 mOsm/kg) that led to a hypooncotic state (COP = 6.2 +/- 1.2 mmHg). Blood chemistries and hemodynamics were recorded every 15 min during CPB. Animals were given additional priming fluid and sodium bicarbonate during CPB to maintain a circuit flow of 85 ml.kg-1.min-1 and arterial pH greater than 7.35. There were no significant differences between groups 1 and 2 with respect to temperature, central venous pressure, mean arterial pressure, PaO2, PaCO2, plasma sodium concentration, or osmolality at any time during CPB, although osmolality increased in both groups. After 60 min of bypass, animals were killed and organ water contents were determined by wet/dry weight ratios. A separate group of nine similarly prepared and anesthetized animals that did not undergo cannulation or CPB also underwent measurement of plasma chemistries and tissue water contents and served as nonbypass controls (group 3). Brain and kidney water contents were unaffected by oncotic pressure, whereas duodenum and skeletal muscle had significantly greater water content (P = 0.003 and P = 0.008, respectively) after hypooncotic CPB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240685 TI - Halothane cooling contractures of skinned mammalian muscle fibers. AB - The effects of halothane or cooling on Ca2(+)-activated tensions and on the uptake and release of Ca2+ by the sarcoplasmic reticulum were investigated in chemically skinned fibers of the extensor digitorum longus muscle of adult rabbits. At 22 degrees C, halothane (greater than 0.46 mM) induced Ca2+ release from the SR of Ca2(+)-loaded skinned fibers that resulted in transient tensions. Higher concentrations of halothane (greater than 4.65 mM) reduced the steady state accumulation of Ca2+ in the SR at 22 degrees C. Cooling (to less than 10 degrees C) elicited transient contractures (cooling-induced contractures [CC]) in Ca2(+)-loaded skinned fibers, despite the fact that the tensions elicited by adding Ca2+ to the bath were depressed at these low temperatures. The skinned fibers did not develop CCs at 12-16 degrees C. Halothane cooling contractures could be elicited at these temperatures by exposing the fibers to halothane concentrations that failed to elicit Ca2+ release at 22 degrees C. The halothane cooling contractures were blocked by procaine but not by lidocaine. It was concluded that these contractures resulted from a synergistic interaction between halothane and cooling that stimulates Ca2+ release from, and reduces Ca2+ uptake by, the sarcoplasmic reticulum. PMID- 2240686 TI - Local and global function of the right ventricle in a canine model of pulmonary microembolism and oleic acid edema: influence of ventilation with PEEP. AB - Right ventricular (RV) dysfunction may occur due to increased RV afterload and, hence, might also contribute to the decrease in cardiac output following institution of PEEP in patients with adult respiratory distress syndrome (ARDS). To test this hypothesis, the authors examined the influence of PEEP on local and global RV function in 12 anesthetized dogs with experimental ARDS (eARDS) induced by pulmonary microembolization with glass beads and oleic acid. Local RV function was analyzed in the RV inflow tract (RVIT) and RV outflow tract (RVOT) by assessing both diastolic segment length, systolic segment shortening, and segment work (sonomicrometry). Global RV contractility was quantified by measuring maximum rate of pressure rise (dRVP/dtmax) and maximum velocity of contractile element shortening (Vmax). In eARDS, despite a fivefold increase in pulmonary vascular resistance, there was no change in cardiac index (CI), global RV contractility, RVIT and RVOT work, and RVIT shortening, whereas RVOT shortening decreased from 12.4 to 7.4% (P less than 0.01). Diastolic segment length increased in RVIT (P less than 0.05) but not in RVOT. PEEP of 10 cmH2O did not alter global RV contractility, RVIT and RVOT shortening, and RVIT work but reduced RVOT work (-35%; P less than 0.01) and CI (-11%; P less than 0.001). Cardiac index further decreased during PEEP of 20 cmH2O (-38%; P less than 0.001), while global RV contractility remained intact despite decreased RVIT and RVOT shortening (-32% and -69%; P less than 0.05) and work (-26% and -59%; P less than 0.01) in the presence of reduced fiber preload in both regions. From these findings, it was concluded that 1) the decreased CI during mechanical ventilation with PEEP at constant right ventricular end-diastolic pressure (RVEDP) is not caused by depressed global RV contractility in dogs with eARDS and a normal myocardium prior to insult. Decreased diastolic segment length and segment shortening during PEEP suggest that 2) PEEP reduces stroke volume by the Starling mechanism rather than by ischemia of the RV free wall. Finally, regionally incongruent changes of fiber preload indicate that 3) local differences in RV wall compliance are likely to occur subsequent to eARDS and PEEP. PMID- 2240687 TI - Differential protective effects of halothane and isoflurane against hypoxic and reoxygenation injury in the isolated guinea pig heart. AB - The authors investigated the effects of halothane (HAL) and isoflurane (ISO) on cardiac depression produced by global hypoxia and the recovery of function following reoxygenation is isolated guinea pig hearts perfused with Krebs' solution at constant pressure. Isovolumetric left ventricular systolic (LVSP) and end-diastolic pressures (LVEDP) were measured by placing a saline filled, latex balloon into the left ventricle. Bipolar electrodes were placed in the right atrium and right ventricle for measurements of heart rate (HR), atrioventricular conduction time (AVCT), and determination of the incidence and severity of dysrhythmias occurring during hypoxia and reoxygenation. Hearts were divided into three groups: control (n = 20), halothane (n = 12), and isoflurane (n = 13). All hearts were exposed in sequence to oxygenated perfusate (PO2, 530 mmHg), moderately hypoxic perfusate (PO2, 91 mmHg) for 30 min, and then to oxygenated perfusate for 40 min. Halothane (1%, 0.4 mM) or isoflurane (1.5%, 0.5 mM) were administered 10 min before hypoxia, during hypoxia, and during the first 10 min of reoxygenation. Exposure to halothane and isoflurane before hypoxia produced a 14 and 11% decrease in heart rate, a 32 and 23% increase in AVCT, and a 47 and 28% decrease in LVSP (all P less than or equal to 0.001) for halothane and isoflurane, respectively, and no significant change in LVEDP. During hypoxia, HR decreased and AVCT increased similarly in both groups. Left ventricular systolic pressure (LVSP) decreased sharply with a narrowing of the prehypoxic differences among the groups. In the control and isoflurane groups, LVEDP increased during hypoxia but remained unchanged in the halothane group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240688 TI - Halothane and isoflurane alter phospholipid transmethylation in rat brain synaptosomes. AB - The mechanism of action of inhalational anesthetics is unknown, but neuronal membrane alteration is a favored hypothesis. Since phospholipid methylation and translocation play a key role in the transmission of biologic signals across cell membranes, we examined the effect of two commonly used halogenated anesthetics, halothane and isoflurane, on phospholipid methylation in rat brain synaptosomes. Using S-adenosyl-L-[3H-methyl]methionine as a donor, we found a two-fold increase in 3H-methyl incorporation into phospholipids in synaptosomes taken from rats exposed to concentrations that just abolish pain response, but not in rats exposed to higher or lower concentrations. Methylation was not increased in rats newly recovered from anesthesia. Halothane added to synaptosomes taken from rats not previously exposed to anesthetics stimulated 3H-methyl incorporation over a wide range of concentrations. Enhancement of phospholipid methylation by halothane and isoflurane may effect an alteration of neural signal transduction that results in the anesthetic state. PMID- 2240689 TI - Adenosine decreases the minimum alveolar concentration of halothane in dogs. AB - Adenosine has sedative properties, and adenosine-receptor agonists have been found to reduce anesthetic requirements in rodents. This study determined whether adenosine, in hypotensive doses, reduces anesthetic requirements in halothane anesthetized dogs. In seven animals, minimum alveolar concentration (MAC) for halothane was determined by a tail-clamp technique at three time points: after 2 h of halothane anesthesia, during adenosine-induced hypotension (mean arterial pressure: 55 mmHg), and 1 h after adenosine was discontinued. In other dogs, the effects of aminophylline, dipyridamole, or the specific adenosine-receptor antagonist 8-phenyl-theophylline (8-PT) on the halothane-adenosine interaction were studied. Adenosine significantly reduced halothane MAC, by 49%, from 0.76 +/ 0.05 to 0.39 +/- 0.05 vol% (mean +/- SEM). This effect was blocked by the concurrent administration of aminophylline (n = 5, P less than 0.05) or 8-PT (n = 4 of 4). When dipyridamole, which increases the plasma concentrations of endogenous adenosine, was administered alone, halothane MAC was reduced from 0.79 +/- 0.03 to 0.67 +/- 0.05 vol% (n = 5, P = 0.09). We conclude that exogenous adenosine substantially reduces halothane MAC in dogs and that this effect is blocked by the concurrent administration of the adenosine-receptor antagonists aminophylline or 8-PT. Relatively small alterations of endogenous adenosine concentrations, however, do not substantially reduce halothane MAC. PMID- 2240690 TI - Ergonomic and human factors affecting anesthetic vigilance and monitoring performance in the operating room environment. PMID- 2240691 TI - [Evaluation of the quality of preoperative electrocardiogram interpretation by anesthesiologists]. AB - This prospective study aimed to assess the quality of interpretation by Teaching Hospital anaesthesiologists of preoperative electrocardiograms (ECG). It was carried out over a period of 7 months, and included 500 patients scheduled for elective surgery. The ECG was first interpreted by the anaesthesiologist during the preoperative visit, and later during the postoperative period, by a cardiologist. The two interpretations were compared using the following criteria: minor anomalies, which would not influence the anaesthetic technique already selected; major anomalies, which, on the other hand, are known to increase anaesthetic morbidity and mortality rates, thereby influencing the choice of anaesthetic technique; and interpretative errors concerning only the major anomalies, i.e. anomalies not seen by the anaesthesiologist (false negatives), anomalies found which did not exist (false positives), and erroneous or incomplete interpretation. Interpretation of the ECG by the anaesthesiologist was written on the anaesthetic record for only 156 patients (31.2%). Among the 500 ECG's, 141 were found to be abnormal by the cardiologist (28.2%). Seventy-three of them had 1 or more major abnormalities. Of the 156 ECG's interpreted by an anaesthesiologist, 64 (41%) were abnormal. The overall error rate was 21.1%, the major error rate being 7.1%. The overall false negative rate was 12.8%, with 7 major ischaemic abnormalities (4.5%) having not been found, including 4 (2.6%) diagnostic errors. About 3.8% of ECG's were wrongly interpreted as abnormal by the anaesthesiologist; all errors were of minor importance, but nevertheless responsible for delayed surgery, loss of time, and extra expenditure in laboratory tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240692 TI - [Risk of thrombosis in prolonged catheterization of the radial artery: comparison of 2 types of catheters]. AB - The thrombosis rate after long-term cannulation of the radial artery was assessed prospectively in 48 intensive care patients randomly assigned to groupe A (polyethylene Leader-Cath 115-09 catheter; n = 50, aged 55 +/- 20 years, 74% male patients) or groupe B (Teflon Viggo Floswitch 4441 catheter; n = 48, aged 58.6 +/ 16 years, 73% male patients). Bedside angiography was carried out with 10 to 15 ml Hexabrix before removal of the catheter. The two groups were similar with regard to anthropometric parameters, used drugs, pathological events during the stay in ICU, arterial cannulation technique and its duration. There was no case of clinically significant ischaemia. The rate of X-ray total arterial thrombosis was 20% in group A, and 2% in group B (p less than 0.01). There was no difference in the rate of partial thrombosis (54% vs. 41.7% respectively, NS) and of lack of thrombosis (26% vs. 56.3% respectively, NS). The overall rate of thrombosis was greater in group A than in group B, but not significantly (74% vs. 43.7% respectively). The duration of arterial cannulation did not influence the rate of thrombosis. However it was higher in males of Group A than in those of Group B (p less than 0.01), when heparin was not given (p less than 0.05); when vaso-active drugs were used (p less than 0.05); and when the time required for cannula insertion was greater than 5 min (p less than 0.01). It is concluded that Teflon catheters are more biocompatible than polyethylene catheters. PMID- 2240693 TI - [Opening of a foramen ovale during liver transplantation. The value of transesophageal echocardiography]. AB - A case is reported of a foramen ovale becoming patent during orthotopic liver transplantation (OLT). The patient had a hepatoma secondary to post-hepatitis cirrhosis. Monitoring included transesophageal echocardiography (TEE). A veno venous shunt between the right femoral, portal and left axillary veins was used so as to maintain the venous return during portal and caval clamping. The patient's haemodynamic state remained quite stable throughout this period, and no vasoactive drug was required. Five min after graft reperfusion, pulmonary arterial pressure increased suddenly (mean PAP: 27 mmHg). TEE revealed paradoxical movements of the atrial septum. Colour coded Doppler ultrasound showed blood flowing from the right to the left atrium through a patent foramen ovale. Fifteen min later, mean PAP decreased (18 mmHg) and TEE no longer showed any flow between the two atria. Several studies have reported transient pulmonary hypertension after unclamping when the donor liver is reperfused. This could induce right ventricular failure, with transient inversion of the atrial pressure gradient, which, in turn, could result in a right-to-left shunt through a patent foramen ovale. TEE can monitor regional and overall left ventricular function as well as the atrial septum. This technique might therefore to be useful for cardiac monitoring during OLT. PMID- 2240694 TI - [Mechanisms and prediction of hemorrhagic complications during surgery of thoraco abdominal aortic aneurysms]. AB - This study, including 33 consecutive patients was designed to assess the haemostatic alterations occurring during repair of thoracoabdominal aneurysms. The surgical procedure consisted in Dacron graft replacement of the diseased aorta, using neither cardiopulmonary bypass, nor any shunting technique, nor any heparin. Blood samples were drawn before anaesthesia, before and 30 min after unclamping, and on the first postoperative day. The measured parameters were: haematocrit, platelet count, bleeding, activated cephalin, thrombin and prothrombin times, and concentrations of fibrinogen, factors V, VII, X and II, anti-thrombin III, proteins C and S, fibrin degradation products, D-dimers, alpha 2-antiplasmin, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor, and serum protein. Eight patients developed severe multiple haemorrhages; 3 of them died during the procedure because of uncontrollable bleeding. Although the measured parameters were similar in the "bleeding" and control (n = 25) groups before surgery, there was, before unclamping in the first group, an important increase in activated cephalin and thrombin times, with a fall in concentrations of factor II and V, protein C, fibrinogen, and alpha 2 antiplasmin, and in platelet numbers. After unclamping, these changes worsened further, with an increase in prothrombin time and in fibrinogen levels (0,8 g.l 1), without any increase in fibrin degradation products. Abnormal bleeding started about 30 min after this in all the patients of the "bleeding" group. These changes, involving the fibrinolytic system as well as a fall in concentration of all the coagulation factors, can probably be partly explained by the clamping and unclamping of mesenteric vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240695 TI - [Clonidine: from the treatment of hypertension to its use in anesthesia. II: Perioperative use]. PMID- 2240696 TI - [Technical constraints in rapid vascular fluid replacement]. AB - Rapid fluid infusion remains the cornerstone for therapy of hypovolaemic shock. The principal limitations of flow rate are governed by the four variables of Poiseuille's law: tube internal diameter and length, viscosity of the fluid passing through the tube, and the pressure gradient between the two ends of the tube. Conventional transfusion systems, with wide bore tubing (up to 5.0 mm internal diameter), large bore cannulas (8.5 French introducer catheters), high pressure (up to 300 mmHg) and diluted blood, can result in a maximum flow rate of about 1,000 ml.min-1 (for crystalloid solutions). Specific apparatus for rapid infusion can increase this to 1,500 ml.min-1 (Rapid Infusion System, Haemonetics). Dry-heat warming devices and microfiltration, to remove microaggregates and prevent non haemolytic febrile transfusion reactions, seem necessary when carrying out rapid transfusions. However, the use of microaggregate filters could be avoided by the routine production of leukocyte poor red blood cell concentrates. PMID- 2240697 TI - [Peroperative pneumothorax in thoracotomy: the value of pulse oximetry]. AB - Two cases of pneumothorax occurring during thoracotomy under one-lung ventilation are reported. One case occurred before pneumonectomy was carried out. The decrease in Spo2 shown by pulse oximetry, together with the increase in airway pressures, rapidly led to the diagnosis of pneumothorax. In the other case, the accident occurred after pneumonectomy, with a suddenly impossible ventilation, and a drastic decrease in Spo2 leading to hypoxic circulatory arrest. Hypoxaemia occurring during one-lung ventilation may be due to different causes. Shunting in the upper part of the lung is the main cause, but other diagnoses must be discussed, such as airway obstruction by blood or sputum, displacement of the selective endotracheal tube, bronchospasm, and pneumothorax. Monitoring of Spo2 by pulse oximetry would therefore seem to be mandatory during thoracic surgery, in order to allow an early diagnosis of hypoxaemia and speed up the treatment of its cause. PMID- 2240698 TI - [Fatal maternal streptococcus A infection after cesarean section]. AB - A case is reported of an infection with Streptococcus pyogenes, occurring 24 hours after an elective Caesarean section in a 30 year old woman. She worsened during the first 48 h, with shock (Pasys less than 70 mmHg, pH 7.28) as well as abdominal tenderness and guarding. Laparotomy revealed peritonitis, and subtotal hysterectomy was carried out. Gram positive cocci were found in the peritoneal exudate, with bacterial cultures yielding Streptococcus pyogenes. Histopathological examination of the specimen revealed necrosing endomyometritis with septic thrombophlebitis. During the immediate post-operative period, there were several prolonged episodes of circulatory arrest treated with dobutamine, adrenaline, and noradrenaline. Multiple organ failure occurred during the next five days, despite antibiotic therapy (vancomycin, tienamycin, amikacin) and intensive care. It included jaundice, thrombocytopaenia (10 G.l(-1] adult respiratory distress syndrome (ARDS). A further laparotomy was carried out because of abdominal and thigh cellulitis, with completion of the hysterectomy and bilateral salpingo-oophorectomy. Streptococcus pyogenes was still present in the peritoneal cavity. There followed an improvement, with a return to normal of the platelet count, haemodynamic stability such that vasoactive drugs were no longer needed, and a decrease in the degree of jaundice. However, the ARDS worsened, and the patient died 15 days after the Caesarean section. There have been recent reports of similar cases, suggesting an increase in the virulence of group A streptococci linked to a re-emergence of exotoxin A. PMID- 2240699 TI - [Venous catheterization and congenital abnormalities of the superior vena cava]. AB - Persistent left superior vena cava is encountered in about 0.3 to 0.4% of human beings. It derives from remnants of the left cardinal vein system. This results in either a duplication of the superior vena cava or in a single left vena cava. The diagnosis is easy in case of associated cardiovascular anomalies. Two cases of single left vena cava and one case of duplication of the superior vena cava are described. All were identified owing to repeatedly aberrant courses of central venous catheters. Diagnosis was easily provided by angiography. Clinical course was uneventful. Despite its usual good tolerance, the persistence of a left vena cava, as an isolated anomaly, must not be neglected as it carries many practical implications which are reviewed. PMID- 2240700 TI - [Hyperkinetic shock and cerebral malaria]. AB - Two cases of cerebral malaria with hyperkinetic shock are reported. The first case concerned a 39-year-old european male who was not taking any prophylactic anti-malarial drugs. After having had headache and fever for a week, he was admitted to the intensive care unit (ICU) in coma and with jaundice. His initial systolic blood pressure was 60 mmg, with a central venous pressure (CVP) of -3 cmH2O. Five-hundred ml of modified fluid gelatin increased the CVP without raising the blood pressure. Haemodynamic investigations revealed a cardiac index (CI) = 5.2 l.min-1.m-2, peripheral arterial resistances (Rsa) = 290 dyn.s.cm-5, oxygen consumption (VO2) = 120 ml.min-1.m-2. Despite treatment with dopamine and dobutamine, the patient died 3 h after his admission, with a CI of 1.9 l.min-1.m 2. The second patient was a 14-year-old senegalese girl, admitted in circumstances similar to the first case. Initial haemodynamic investigations gave the following figures: CI 6.5 l.min-1.m-2, Rsa = 476 dyn.s.cm-5, VO2 = 174 ml.min 1.m-2. Recovery was obtained with fluid replacement therapy and dopamine. In the absence of another associated infectious disease, the plasmodial origin of the septic shock would seem to be the most likely in both cases. Pathophysiological mechanisms of these algid forms of malaria remain enigmatic. Various factors are discussed: cytoadherence of erythrocytes infected with Plasmodium falciparum, immunological disturbances, or a specific endotoxin. PMID- 2240702 TI - [Separate lung respiration and interatrial defect]. PMID- 2240701 TI - [Respiratory tract obstruction caused by ballooning of an intubation tube cuff during nitrous oxide inhalation]. AB - A typical case of upper airway obstruction due to deformation of a low pressure tracheal tube cuff is reported. It would seem that this herniation may have been due to nitrous oxide diffusing with in the air-filled cuff, thereby causing it to overdistend. This increase in pressure occurred after 3 hours of inhalation of a mixture of oxygen and nitrous oxide. The deformed cuff may either block the lumen at the end of the tube, or push the tube against the tracheal wall. The result is, in either case, a mechanical obstruction of the airway, with hypoxia, and then anoxia. In the reported case, it was the decrease of SpO2 which alerted the anaesthetist. Pulse oximetry was helpful for an early diagnosis. To avoid such accidents, it is suggested either to inflate the cuff with the gas mixture with which the patient is ventilated, or to deflate it every 30 min. PMID- 2240704 TI - [Moderate von Willebrand's disease type I: use of desmopressin]. PMID- 2240703 TI - [Cardiocirculatory arrest during anesthesia with propofol and fentanyl]. PMID- 2240705 TI - [Preoperative use of desmopressin in a woman treated by ticlopidine]. PMID- 2240706 TI - [Anesthesia and factor VII deficiency]. PMID- 2240707 TI - [History taking and thrombosis]. PMID- 2240709 TI - [Plea for humanitarian anesthesia]. PMID- 2240708 TI - [Occupational peroperative accident caused by atropine]. PMID- 2240710 TI - Optimization of pulse train duration for the electrical stimulation of a skeletal muscle ventricle in the dog. AB - The optimal means of electrically stimulating a skeletal muscle to contract around a fluid-filled pouch (i.e., a skeletal muscle ventricle [SMV]) has not been determined. A SMV was made from the latissimus dorsi muscle in five dogs and the rectus abdominis muscle in five dogs, and each SMV was electrically stimulated via the motor nerve(s) to contract around a fluid-filled pouch, which was connected to a mock circulatory system. The pulse train duration (PTD) was varied from 100 ms to 800 ms in 100 ms increments to determine the effect of this variable upon SMV output. The pulse width of the electrical stimulus was kept constant at 100 microseconds and the pulse frequency was maintained at 50 s-1. For SMV contraction rates of 20, 30, and 40 min-1, the optimal PTD was 400 ms for both muscles. The peak output was 710 ml min-1 for the rectus SMV and 556 ml min 1 for the latissimus SMV. For an SMV contraction rate of 10 min-1, the optimal PTD was 800 ms for the rectus SMV and 600 ms for the latissimus SMV. Use of less than an optimal PTD caused reductions in SMV output of 25-50%. Although SMVs made from rectus abdominis and latissimus dorsi had similar values for the optimal PTD, the maximum SMV output was usually greater with the rectus abdominis in this acute study with untrained muscles. We conclude that PTD is an important variable to control, which can markedly affect results when studying the potential use of skeletal muscle power for cardiac assistance. PMID- 2240711 TI - Human skeletal muscle: phasic type of electrical stimulation increases its contractile speed. AB - Skeletal muscles, exposed to a prolonged period of specific functional demands, respond adaptively. Electrical stimulation, when employed as a technique for subjecting selected muscles to altered use, enables precise entrainment of the pattern of functional activity. In this investigation, the vastus lateralis muscle in a group of volunteers was stimulated. The stimulation program typical of a phasic type of activity (high frequency, high current amplitude, short pulse duration) intermittently subjected the stimulated muscles to brief periods of intense activity, followed by relatively long pauses. The activation-relaxation time ratio chosen was 1 to 13. It was determined to prevent the muscles from fatiguing. The effects of the chronic stimulation program were established by measurements of the time course of contraction and relaxation and fatigue of the vastus lateralis muscle. Chronic phasic electrical stimulation increased the speed of muscle contraction by 15% while the fatigue characteristics remained unchanged. PMID- 2240713 TI - Nonlinear phenomenon of interfacial polarization immittance of a Pt electrode. AB - Description of a computerized, automated method to measure the interfacial polarization immittance of a Pt electrode in nonlinear range is presented. The classical three-electrode setup is used for measurements in conjunction with a special purpose software implemented on a Unix computer using C language. A collection of data at very low frequencies (below 2 Hz) and at high input intensities with various dc biases imposed on the input are presented to show the behavior of the interface in nonlinear range. The instrument also provides on line harmonic analysis of the output signal, by calculating the first four Fourier series coefficients, in response to a pure sinusoidal input. PMID- 2240712 TI - Isolated aorta setup for hemodynamic studies. AB - A setup consisting of a high-performance hydraulic pump connected to the ascending part of an isolated aorta, including all major distal branches, each loaded with calibrated artificial resistors, was developed. The system was used to study total aortic compliance of the baboon as a function of mean aortic pressure (n = 5). The aorta loaded with the resistors was mounted in a custom designed sink table, such that it was submersed in physiological saline maintained at 37 degrees C. Mean distending pressure in the entire aorta could be varied. The three-element Windkessel model was used to estimate total aortic compliance from pressure and flow waves generated by the pump. Total aortic compliance as a function of mean pressure was fitted with a logarithmic function: Ln(Compliance) = A + B * P. The value of A (+/- SE) was: 1.565 +/- 0.319 and B: 0.020 +/- 0.003 (P less than 0.001). The results were compared with previously published results (also using the same three-element Windkessel fit) obtained in three of the same animals in vivo. The in vivo data were A: 1.095 +/- 0.235 and B: B: -0.019 +/- 0.003. In vitro data had a significantly higher value of A than in vivo (P = 0.017), implying a significantly higher aortic compliance in vitro than in vivo. Occlusion of the proximal descending aorta was performed at a low distending pressure (55 mm Hg) to determine the proximal compliance. It was found (n = 4) that 46 +/- 11% (SD) of the total arterial compliance is to be attributed to the ascending and proximal descending aorta. PMID- 2240714 TI - A new geometric procedure for in vivo pulsed Doppler evaluation of velocity distribution inside the diametrical section of large arteries in humans. AB - A new geometric procedure determination of velocity profiles inside large human arteries, such as the brachial and femoral, has been developed. The procedure requires the use of two crystal element Doppler probes and a highly precise micromanipulator with three degrees of freedom. Precise positioning is needed to obtain the required high degree of parallelism between the vessel axis and the plane containing the two crystal elements. Once the appropriate degree of parallelism is achieved, a controlled translation of the probe, perpendicular to the ultrasonic beam plane, allows velocity waveforms to be recorded at sequential radial positions across the measured artery. Velocity profiles obtained with this geometric procedure depended on the type of artery investigated. The profiles measured with the geometric procedure were more symmetrical than those found using the electronic range-gated time system of reception. While the geometric and electronic methods were almost identical in determining the diameter values of the three arteries measured, the geometric procedure enabled greater accuracy for detailed analysis of velocity profiles in the peripheral large arteries in humans. Although the present methodology is not applicable in clinical practice due to prolonged data acquisition time (approximately 45 s) it is expected that future equipment improvements will reduce this time significantly. PMID- 2240716 TI - Hemodynamic determinants of subdiaphragmatic venous return during closed-chest CPR in a canine cardiac arrest model. AB - OBJECTIVE: To assess the hemodynamic determinates of peripheral subdiaphragmatic venous-to-right-heart return during closed-chest CPR. MODEL: Seven anesthetized dogs subjected to electrically induced ventricular fibrillation for five minutes. INTERVENTIONS: Conventional closed-chest CPR and closed-chest CPR with continuous abdominal binding at a chest compression rate of 60 per minute, a compression-to relaxation ratio of 50:50, and a ventilation-to-compression ratio of 1:5. METHODS: Solid-state catheters were positioned in the ascending aorta, right atrium (RA), and inferior vena cava (IVC). Cannulating electromagnetic flow probes were inserted into the IVC and a carotid artery. Analog-to-digital conversion was performed electronically. Five minutes after ventricular fibrillation was induced, interventions were performed in an alternating sequence. Systolic, diastolic, and mean pressures and flows were measured and compared. STATISTICAL METHODS: Two-tailed, unpaired t test applied to equal sample size, linear regression analysis, and multiple regression analysis. RESULTS: Abdominal binding during CPR significantly increased (P less than .05) all measured systolic and diastolic CPR intravascular pressures compared with CPR without abdominal binding but did not affect IVC-to-right-heart venous return. During conventional CPR without abdominal binding, venous return was dependent on the diastolic IVC pressure (r = .86, P = .014), mean IVC pressure (r = .80, P = .03), and carotid blood flow (r = .99, P = .001) but not on the IVC-to-RA pressure gradient. With abdominal binding, venous return was not correlated with any study hemodynamic variable, including the peripheral venous-to-RA pressure gradient. CONCLUSION: Venous return from the subdiaphragmatic venous bed during CPR is dependent on venous pressure, not on the peripheral venous-to-right-heart pressure gradient. Abdominal binding during CPR does not affect venous return. Venous return during CPR diastole is highly dependent on central venous capacitance (left heart outflow during CPR systole). PMID- 2240717 TI - Manual translaryngeal jet ventilation and the risk of aspiration in a canine model. AB - STUDY OBJECTIVES: Manual translaryngeal jet ventilation (TLJV) is a safe and effective method of maintaining normal ventilation in apneic subjects. Little data exist on the amount of airway protection afforded with this technique of airway management. We sought to evaluate the risk of aspiration during manual TLJV. SETTING: Data were collected in a laboratory animal model. DESIGN: A prospective, nonrandomized, controlled trial was performed. PARTICIPANTS: Seventeen adult apneic mongrel dogs were enrolled. INTERVENTIONS: Intratracheal Gastrograffin was instilled and radiographic changes assessed during ventilation using a 0 to 3 scale (none to severe). Thirty-six trials were performed, with equal numbers at both 30 degrees and 45 degrees head elevation. The three groups studied were animals without airway protection (control), animals with a cuffed endotracheal tube (tube), and animals with a percutaneous TLJV cannula and a 50 psi oxygen source ventilated at a rate of 20 breaths per minute (jet). MEASUREMENTS AND MAIN RESULTS: Significantly less radiographic evidence of aspiration was noted in the jet and tube groups at 30 degrees and 45 degrees compared with control animals (P = .002 each). At 45 degrees head elevation a trend toward increased aspiration scores in the jet group compared with the tube group (P = .065) was observed. CONCLUSION: In our model, manual TLJV at 20 breaths per minute and an I:E ratio of 1:2 provided protection from aspiration comparable to that observed with a cuffed endotracheal tube at 30 degrees head elevation. At 45 degrees elevation, this protection was diminished. PMID- 2240715 TI - Noninvasive assessment of mechanical properties of peripheral arteries. AB - An ultrasound examination was used to noninvasively determine the changes in mechanical properties associated with age for the common carotid, brachial, popliteal, femoral, and tibial arteries. Forty-two normal male subjects, ranging in age from 8 to 60 years of age, were examined. The subjects were placed in one of three age groups: less than 29 years of age, 29 to 38, and greater than 38. Mechanical properties including percentage variation in diameter, pressure strain, and circumferential elastic modulus were determined from changes in wall thickness and pulse pressure. Percentage variation in diameter (PVD) was seen to decrease with age for all arteries except the brachial, which remained relatively constant. Pressure-strain (Ep) and circumferential elastic moduli (Eo) were seen to increase with age in all arteries except the brachial, which remained relatively constant. Values of Ep and Eo were normalized into a stiffness index by dividing by the value found for the brachial artery. Stiffness indexes for the common carotid and femoral arteries were observed to increase more rapidly with age than the indexes obtained for the popliteal and tibial arteries. It is proposed that the stiffness index and changes in this parameter that occur with age may be useful in noninvasively assessing the progression of atherosclerosis. PMID- 2240718 TI - Stability of epinephrine in alkalinized solutions. AB - STUDY OBJECTIVE: Increasing the pH of an epinephrine solution favors its oxidation and may result in a decrease in its biological activity. It is therefore generally assumed that epinephrine and sodium bicarbonate should not be infused in the same IV line during CPR. The aim of this study was to determine the validity of this widely accepted proposition. DESIGN AND SETTING: Two different commercial solutions of epinephrine differing only in the concentration of sodium metabisulfite (0.46% and 0.02%) were studied. Two dosages of each solution type (1 mg/1 mL and 10 mg/10 mL) were diluted in 250 mL of 8.4% sodium bicarbonate. MEASUREMENTS AND MAIN RESULTS: The concentration of epinephrine was measured at different times for two weeks. It was found that the concentration of epinephrine decreased slowly to zero after two weeks, and was approximately at 70% and 100% of control values at 30 minutes after alkalinization. CONCLUSION: It was concluded that epinephrine in an alkaline solution is effectively oxidized but has a slow reaction that may not be clinically relevant over short periods of time. PMID- 2240719 TI - Encouraging early defibrillation: the American Heart Association and automated external defibrillators. PMID- 2240720 TI - Survival rates from out-of-hospital cardiac arrest: recommendations for uniform definitions and data to report. AB - Survival rates for out-of-hospital cardiac arrest vary widely among locations. We surveyed the definitions used in published studies of out-of-hospital cardiac arrest. Data from 74 studies involving 36 communities showed survival rates ranging from 2% to 44%. There were five different case definitions and 11 different definitions of survivors. The absence of uniform definitions prevents meaningful intersystem comparisons, prohibits explorations of hypotheses about effective interventions, and interferes with the efforts of quality assurance. The most satisfactory numerator for a survival rate appears to be survival to hospital discharge; the most appropriate denominator appears to be witnessed adult cardiac arrest of presumed heart disease etiology, with ventricular fibrillation as the initial identified rhythm. Proposed definitions for the data emergency medical services systems should report as they examine their cardiac arrest survival rates are presented. PMID- 2240721 TI - Activity-sensing permanent internal pacemaker dysfunction during helicopter aeromedical transport. AB - STUDY OBJECTIVES: This study was designed to establish the frequency, magnitude, and possible etiologies of the dysfunction of activity-sensing internal pacemakers during helicopter aeromedical transport. DESIGN: Two models of Medtronic Activitrax pacemakers were attached externally to healthy adult volunteers. Each volunteer then was loaded into the helicopter and subjected to a flight sequence. Pacemaker firing rates throughout this sequence were recorded. SETTING: On separate days, Aerospatiale Dauphin and Twinstar helicopters completed a total of 23 flights. TYPE OF PARTICIPANTS: Four healthy adult volunteers, two men and two women, participated. INTERVENTIONS: These included intra- and inter-flight threshold re-programming and external magnet application. RESULTS: The average preflight pacemaker rate of 65 beats per minute increased to an average in-flight rate of 105 beats per minute, which resolved to preflight rates on shutdown. This pattern was consistently extinguished with external magnet application. CONCLUSION: The effect of rotor motion and flight vibration on the rate-response of the Activitrax pacemaker is both predictable and easily preventable. Possible guidelines for the safe transport of these patients, using pacemaker reprogramming or external magnet application, are examined. PMID- 2240722 TI - Prehospital cardiac arrest: the impact of witnessed collapse and bystander CPR in a metropolitan EMS system with short response times. AB - OBJECTIVE: Numerous studies have shown initiation of bystander CPR to significantly improve survival from prehospital cardiac arrest. However, in emergency medical services (EMS) systems with very short response times, bystander CPR has not been shown to impact outcome. The purpose of this study was to determine the effect of bystander CPR on survival from out-of-hospital cardiac arrest in such a system. DESIGN: Prehospital, hospital, and death certificate data from a medium-sized metropolitan area were retrospectively analyzed for adult, nontraumatic cardiac arrest during a 16-month period. RESULTS: A total of 298 patients met study criteria. One hundred ninety-five arrests (65.4%) were witnessed, and 103 (34.6%) were unwitnessed. Twenty-five witnessed victims (12.8%) were discharged alive, whereas no unwitnessed victims survived (P less than .001). Patients suffering a witnessed episode of ventricular fibrillation/tachycardia (VF/VT) were more likely to survive (21.9%) than were other patients (2.0%, P less than .0001). Among witnessed patients, initiation of bystander CPR was associated with a significant improvement in survival (20.0%) compared with the no-bystander CPR group (9.2%, P less than .05). Bystander CPR was also associated with improved outcome when witnessed patients with successful prehospital resuscitation were evaluated as a group; 18 had bystander CPR, of whom 13 (72.2%) survived compared with only 12 of 38 patients with no bystander CPR (31.6%, P less than .01). CONCLUSION: Our data revealed improved survival rates when bystander CPR was initiated on victims of witnessed cardiac arrest in an EMS system with short response times. PMID- 2240723 TI - Prehospital data entry compliance by paramedics after institution of a comprehensive EMS data collection tool. AB - OBJECTIVE: To determine the completeness of data entry by paramedics after an extensive modification of the prehospital first-care form in an urban emergency medical services (EMS) system. DESIGN: Comprehensive medical information was added to the EMS data collection tool used by a metropolitan fire department. We evaluated the frequency of failure to enter data pertaining to medical assessment and/or treatment of victims of cardiac arrest after implementation of the system. RESULTS: Failure to enter data in the first month was compared with two subsequent two-month blocks. A high rate of noncompliance existed in the first month (all medical data were missing in 24.6%). However, the subsequent two months revealed a marked decline in noncompliance (4.4%, P less than .001). This decline was maintained after a three-month interim (5.0%, P less than .001). CONCLUSION: Data entry noncompliance can be a significant problem after implementation of a new prehospital data collection system. However, compliance can be markedly improved over a relatively short period. Because EMS system evaluation is based on data collected in the field. EMS researchers and administrators must be aware of the data entry compliance rate in their system when attempting to make conclusions from such information. PMID- 2240724 TI - Prehospital prophylactic lidocaine does not favorably affect outcome in patients with chest pain. AB - STUDY OBJECTIVES: The purpose of our study was to determine the morbidity and mortality in initially stable patients presenting to paramedics with chest pain; to examine possible beneficial effects of its use, including reduction of sudden death syndrome in the prehospital and emergency department setting; and to determine if prophylactic lidocaine is associated with adverse effects in this patient population. DESIGN AND SETTING: This was a randomized, prospective study using prophylactic lidocaine in patients complaining of chest pain who presented to our paramedic system between January 1984 and January 1988. TYPE OF PARTICIPANTS: All patients aged 18 years or older with chest pain of suspected cardiac origin who presented to paramedics during the study period were included. Excluded were patients presenting with warning arrhythmias, second- or third degree heart block, bradycardias of less than 50, hypotension of less than 90 mm Hg systolic, or known allergy to lidocaine. INTERVENTIONS: Patients were randomized into two groups, the lidocaine-treated group and the control group. An initial bolus of 1 mg/kg IV lidocaine was administered to the lidocaine-treated group. A simultaneous 2 mg/min IV drip was established. Ten minutes after the first dose of lidocaine, a second bolus of 0.5 mg/kg was administered. MEASUREMENTS AND MAIN RESULTS: During the study period, 1,427 patients were entered; 704 received lidocaine, and 723 did not. Discharge diagnoses included acute myocardial infarction (31%), unstable angina (33%), other cardiac problems (7%), and noncardiac problems (29%); overall mortality rate was 7.4%. There was an equal distribution of deaths between the lidocaine-treated group (57) and the control group (48). Six patients had a cardiac arrest in the prehospital setting, and 15 had a cardiac arrest in the ED. Malignant ventricular arrhythmias as the precipitating arrest rhythm in patients with acute myocardial infarctions were similar for the lidocaine-treated and control groups. The incidence of adverse effects, including hypotension, bradycardias, second- or third-degree heart blocks, tinnitus, and altered mental status, was similar in both groups. CONCLUSION: There are no benefits from the administration of prehospital prophylactic lidocaine in stable patients with chest pain; therefore, routine use in this setting appears unwarranted. PMID- 2240725 TI - The diagnostic impact of prehospital 12-lead electrocardiography. AB - STUDY HYPOTHESIS: It is feasible to apply prehospital 12-lead electrocardiography to most stable prehospital chest pain patients. Prehospital diagnostic accuracy is improved compared with single-lead telemetry. POPULATION: One-hundred sixty six stable adult patients who sought paramedic evaluation for a chief complaint of nontraumatic chest pain. METHODS: One-hundred fifty-one prehospital 12-lead ECGs of diagnostic quality were obtained by paramedics on 166 adult patients presenting with nontraumatic chest pain. Paramedics and base station physicians were blinded to the information on acquired prehospital 12-lead ECGs and treated patients according to current standard of care-clinical diagnosis and single-lead telemetry. Final hospital diagnoses were classified into three groups: acute myocardial infarction (24); suspected angina or ischemia (61); and nonischemic chest pain (66). Paramedics and base station physicians' clinical diagnoses and prehospital and emergency department ECGs were similarly classified and compared. Prehospital and ED 12-lead ECGs were read retrospectively by two cardiologists. RESULTS: Paramedics achieved a high success rate (98.7%) in obtaining diagnostic quality prehospital 12-lead ECGs in 94.6% of eligible prehospital patients. For patients with acute myocardial infarction, prehospital ECG alone had significantly higher specificity than did the paramedic clinical diagnosis (99.2% vs 70.9%; P less than .001), and significantly higher positive predictive value (92.9% vs 32.7%; P less than .001). For patients with angina, combining the paramedic clinical diagnosis and the prehospital ECG significantly improved sensitivity (90.2% vs 62.3%; P less than .001) and increased negative predictive value (88.9% vs 71.3%; P less than .02) compared with paramedic clinical diagnosis alone. There was a high concordance between prehospital and ED ECG diagnosis (99.3% for acute myocardial infarction and 92.8% for angina). Furthermore, ten patients whose prehospital ECGs demonstrated ischemia and who had final hospital diagnoses of angina or acute myocardial infarction were mistriaged by paramedics and/or received no base station physician-directed therapy. CONCLUSION: It is feasible to apply prehospital 12-lead electrocardiography to most stable prehospital chest pain patients. Prehospital 12-lead ECGs have the potential to significantly increase the diagnostic accuracy in chest pain patients, approach congruity with ED 12-lead ECG diagnoses, and may allow for consideration of altering and improving prehospital and hospital-based management in this patient population. PMID- 2240726 TI - Epinephrine in cardiac arrest: a critical review. PMID- 2240727 TI - Delayed splenic rupture. PMID- 2240728 TI - A basic resource guide for emergency medicine research. PMID- 2240729 TI - The delta (delta) gap: an approach to mixed acid-base disorders. AB - The anion gap (AG) is a helpful, yet underused, clinical tool. Not only does the presence of a high AG suggest a certain differential, but knowledge of the relationship between the rise in AG (delta AG) and the fall in bicarbonate (delta HCO3) is important in understanding mixed acid-based disorders. Simple arithmetic converts this relationship into a numerical value, the delta gap (delta gap). The delta gap = delta AG - delta HCO3. If the delta gap is significantly positive (greater than +6), a metabolic alkalosis is usually present because the rise in AG is more than the fall in HCO3. Conversely, if the delta gap is significantly negative (less than -6), then a hyperchloremic acidosis is usually present because the rise in AG is less than the fall in HCO3. Familarity with the relationship between the changes in AG and HCO3 can be useful in unmasking occult metabolic disorders. PMID- 2240730 TI - Plasma lidocaine levels and PaO2 with endobronchial administration: dilution with normal saline or distilled water? AB - STUDY OBJECTIVE: To determine whether water or 0.9% saline should be used as diluent for endobronchial drug administration. PARTICIPANTS: Twelve adult patients. INTERVENTIONS: Patients were endobronchially administered 2 mg/kg lidocaine as marker substance in either 10 mL 0.9% saline or 10 mL distilled water during general anesthesia. MEASUREMENTS AND MAIN RESULTS: The differences in mean lidocaine plasma levels at five minutes (water vs saline, 2.35 vs 1.59 micrograms/mL) and ten minutes (water vs saline: 2.67 vs 1.88 micrograms/mL) were significant (P less than .05). With the initial mean PaO2 being almost (157 mm Hg; F1O2, 0.3) in the two groups, there was a mean drop of about 60 mm Hg in the saline-diluent group, but only about 40 mm Hg in the water-diluent group one minute after administration (P less than .05). CONCLUSION: The use of water resulted in better absorption of lidocaine and less impairment of the PaO2. PMID- 2240731 TI - Rapid visual colorimetry of peritoneal lavage fluid. AB - STUDY HYPOTHESIS: That visual colorimetry can be used to rapidly and precisely estimate the erythrocyte count of 1:5 dilutions of simulated peritoneal lavage fluid. POPULATION: Fifty-four normal adult human subjects. METHODS: The automated or chamber RBC count is often used on fluid obtained by peritoneal lavage in patients with abdominal trauma to help determine the need for surgery. Unfortunately, this method sometimes results in excessive delay. We designed and built a simple colorimeter that facilitated rapid direct visual comparison of unknown samples with known color standards. A radiograph view box was used as a light source. Standards were prepared in 16-mm glass tubes to simulate peritoneal lavage fluid with RBC counts ranging from 0 to 140,000 in 10,000 cell/microL increments; 1:5 dilutions with water were used throughout to reduce opacity. Thimerosal was added to unknowns and standards to stabilize color; all samples were kept refrigerated at 4 C when not in use. In a double-blind in-vitro study, each subject matched 20 randomly distributed unknowns ranging from 12,000 to 131,000 erythrocytes/microL to the nearest standard. RESULTS: The mean absolute error for all 1,080 determinations was 3,560 RBC/microL (95% CI = 4,290-4,830; SD = 4,560; t = 39.6; df = 1,079; P less than .001). This method correctly predicted the RBC count to within 9,000 cells/microL 95% of the time. CONCLUSION: Visual comparison of 1:5 dilutions of simulated peritoneal lavage fluid with known color standards can be used to rapidly and precisely estimate the erythrocyte count. PMID- 2240732 TI - Effect of education on the use of universal precautions in a university hospital emergency department. AB - STUDY OBJECTIVES: To determine if an educational program would improve both knowledge and practice of universal precautions by nursing personnel. DESIGN: Participants were given a 14-question test and observed for their, practice of universal precautions during routine IV catheter placement or phlebotomy and trauma care before and six months after an education in-service. SETTING: University hospital emergency department. TYPE OF PARTICIPANTS: Nursing personnel. INTERVENTIONS: One-hour lecture addressing the occupational risk of human immunodeficiency virus (HIV) infection and the recommended use of universal precautions. MEASUREMENTS AND MAIN RESULTS: The mean overall correct response rates to the questionnaire before and after the in-service were 70% and 73%, respectively (P = NS). The pattern of incorrect responses suggested that the perceived risks of HIV transmission are underestimated, particularly among healthy-appearing patients. For care of critical trauma patients, there were significant increases between the frequency rates before and after the in-service of glove and protective eyewear use (66.7% vs 87.7%, P less than .025; 0.0% vs 17.3%, P less than .05, respectively). The frequency rates of glove use for IV placement or phlebotomy in noncritical patients and of gown use for trauma patient care also increased (52.6% vs 65.2% and 25% vs 39.5%, respectively); however, these changes were not statistically significant. CONCLUSION: An intensive educational program was associated with a modest increase in the compliance of ED nursing personnel with universal precautions and had no long term effect on their general knowledge of HIV risk. The practice of universal precautions is still far from universal in this ED. PMID- 2240733 TI - Scapular dislocation (locked scapula). AB - We report the case of a 19-year-old woman who presented to the emergency department with pain and inability to move her right shoulder after falling backwards and striking it on a cart. Radiographs of the shoulder revealed a dislocated scapula. Closed reduction in the ED was successful. This rare case of scapular dislocation serves to emphasize that a heightened awareness for this injury is necessary if it is to be recognized and treated appropriately. Its treatment and prognosis are reviewed. PMID- 2240734 TI - Toxic streptococcal syndrome. AB - The streptococcal toxic shocklike syndrome is a recently recognized, multisystem disorder that shares many of the features of staphylococcal toxic shock syndrome, but is caused by toxins elaborated by group A beta-hemolytic Streptococcus. We describe a patient who fulfilled the major criteria for the clinical diagnosis of toxic shock syndrome (fever, hypotension, multisystem dysfunction, and diffuse macular erythroderma followed by desquamation) and who demonstrated serologic evidence suggesting streptococcal infection. In patients presenting with clinical findings consistent with a toxic shocklike syndrome, the emergency physician should consider streptococcal infection as a potential etiology. PMID- 2240735 TI - Successful CPR in a severely hypothermic patient using continuous thoracostomy lavage. AB - Severe hypothermia with cardiopulmonary arrest often requires prolonged resuscitation while rewarming procedures are implemented. A 63-year-old male in cardiopulmonary arrest with a core body temperature of 23.7 C was resuscitated successfully after core rewarming by means of a two-chest-tube continuous thoracostomy lavage procedure. This lavage procedure resulted in effective and rapid rewarming after other conventional rewarming methods had failed. PMID- 2240736 TI - Is emergency medicine research viable? PMID- 2240737 TI - Annals & academic respectability. PMID- 2240738 TI - Prophylactic lidocaine. PMID- 2240739 TI - From pain to reperfusion: what role for the prehospital 12-lead ECG? PMID- 2240740 TI - Serologic findings in Lyme disease. PMID- 2240741 TI - Sensitivity, specificity & positive & negative predictive values. PMID- 2240742 TI - Echocardiography to rule out metastatic disease. PMID- 2240743 TI - Complications from hyperbaric oxygen therapy? PMID- 2240744 TI - Additional causes of priapism. PMID- 2240745 TI - Early detection of acute myocardial infarction in patients presenting with chest pain and nondiagnostic ECGs: serial CK-MB sampling in the emergency department. AB - STUDY OBJECTIVES: Patients presenting to the emergency department with chest discomfort are a difficult problem for emergency physicians. Nearly 50% of patients with acute myocardial infarction (AMI) will initially have nondiagnostic ECGs on ED presentation. The purpose of this study was to determine if patients with AMI having nondiagnostic ECGs could be identified using new immunochemical assays for serial CK-MB sampling in the ED. DESIGN: Chest pain patients, more than 30 years old, with pain not caused by trauma or explained by radiographic findings, were eligible for the study. Serial serum samples were drawn on ED presentation (zero hours) and three hours after presentation, then analyzed for CK-MB using four immunochemical methods and electrophoresis. Standard World Health Organization criteria were used to establish the diagnosis of AMI, including new Q-wave formation or elevation of standard in-hospital serum cardiac enzyme markers. SETTING: A tertiary cardiac care community hospital. MEASUREMENTS AND MAIN RESULTS: The serum from 183 patients hospitalized for possible ischemic chest pain was collected and analyzed. Thirty-one of 183 patients (17%) were found to have AMI by standard in-hospital criteria. Sixteen of the 31 patients (52%) with AMI had nondiagnostic ECGs on presentation. Immunochemical determination of serial CK-MB levels provided a sensitive and specific method for detecting AMI in patients within three hours after ED presentation compared with standard electrophoresis. The four immunochemical methods demonstrated a range in sensitivity from 50% to 62.1% on ED presentation versus 92% to 96.7% three hours later. The immunochemical tests demonstrated specificities ranging from 83.0% to 96.4% at three hours, with three of the four tests having specificities of 92% or greater. Electrophoresis had a sensitivity of 34.5% on ED presentation, increasing to 76.9% at three hours, with a specificity of 98.6%. CONCLUSIONS: Immunochemical CK-MB methods allowed rapid, sensitive detection of AMI in the ED. Early detection of AMI offers many potential advantages to the emergency physician. Early detection of AMI, while the patient is in the ED, could direct disposition of this potentially unstable patient to an intensive care setting. Such information may prevent the ED discharge of patients with AMI having nondiagnostic ECGs. The diagnosis of AMI within a six-hour period after symptom onset may allow thrombolytic therapy to be given to patients with AMI not having diagnostic ECGs. This study served as a pilot trial for a multicenter study of the Emergency Medicine Cardiac Research Group, which is currently ongoing. PMID- 2240746 TI - Transtelephonic defibrillation. AB - STUDY OBJECTIVES: This study was undertaken to assess the safety and reliability of a device for transtelephonic defibrillation. DESIGN: The transtelephonic system consists of a patient unit and a base station. The patient unit contains a monitor-defibrillator, electrode pads, microphone, microprocessor, and DC defibrillator. The base station comprises a control panel, computer, and ECG display. SETTING: Fifteen patients who were treated in our emergency department for cardiac arrest were placed on patient units that activated our base station in a remote location within the ED. TYPE OF PARTICIPANTS: Thirteen patients were treated for ventricular fibrillation, and two patients were treated for ventricular tachycardia. INTERVENTIONS: Thirty-one shocks were delivered transtelephonically. MEASUREMENTS AND MAIN RESULTS: In all cases, voice and ECG transmission were established without difficulty. CONCLUSIONS: We conclude that this system represents a safe and reliable method for the treatment of ventricular fibrillation, and we advocate additional use to study the prehospital applications of transtelephonic defibrillation. PMID- 2240747 TI - The validity and reliability of the navicular fat stripe as a screening test for detection of navicular fractures. AB - STUDY OBJECTIVE: The purpose of this study was to determine if the navicular fat stripe (NFS) is a valid and reliable screening tool in assessing potential navicular fractures. DESIGN: Retrospective analysis. SETTING: Minor trauma section of the Los Angeles County-University of Southern California Medical Center emergency department. TYPE OF PARTICIPANTS: Study population included patients seen for wrist injury between January 1987 and December 1988. The individuals who interpreted the radiographs included eight observers with varying degrees of radiographic experience. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: The positive predictive value averaged 12% or 15% depending on how we counted a straight NFS, and the negative predictive value averaged 93% or 95%, again depending on how we counted a straight NFS. A straight NFS was ten times as likely to occur among normal wrists than among those with navicular fractures. Interobserver reliability was found to be high with a Hoyt reliability coefficient of .79. CONCLUSIONS: An abnormal NFS is a poor predictor of a navicular fracture while both a straight and a normal NFS are good predictors of no navicular fracture. A normal NFS may allow less stringent treatment by the emergency physician. Extremes of radiographic experience were found to have no significant effect on NFS interpretation. PMID- 2240748 TI - Tetanus immunization status and immunologic response to a booster in an emergency department geriatric population. AB - STUDY OBJECTIVES: Although effective procedures for the prevention of tetanus have long been available, serosurveys done since 1977 demonstrate that 49% to 66% of the elderly population lacks a protective antitoxin level (more than 0.01 IU/mL). This study was undertaken to assess the tetanus immunization status of patients presenting to an emergency department and to evaluate their immunologic response to a tetanus booster. SETTING: The study was conducted in a tertiary care ED. TYPE OF PARTICIPANTS: The patients enrolled were 65 or more years old and had breaks in their skin barriers. DESIGN: At each patient's initial presentation, pertinent demographic data and tetanus immunization history were recorded. The patient was then followed for 21 days. INTERVENTIONS: Each patient's antitoxin titer was determined on a serum sample by ELISA, and, if required by the Advisory Committee on Immunization Practices criteria, a booster was administered at the first visit. MEASUREMENTS AND MAIN RESULTS: Serum antitoxin assays were repeated on days 7, 14, and 21 after the initial visit until seroconversion (titer more than 0.01 IU/mL). Forty-four patients (55%) had protective levels at initial presentation, and in 36 (45%) the levels were not protective. Age and sex were not predictive of protection. Past military service and a definite history of three or more previous immunizations were good predictors of protection. Of 34 patients who were followed serially for inadequate initial titers, only 19 (56%) seroconverted by day 14. Patients who did not seroconvert were more likely to be older (P less than .05). CONCLUSIONS: This study demonstrated that a significant number of elderly patients lacked an initial protective level of tetanus antitoxin. Of these, 44% failed to seroconvert within 14 days and carried a potential risk of developing tetanus. PMID- 2240749 TI - Acute abdominal pain in the elderly. AB - STUDY OBJECTIVES: To determine the incidences of both specific diagnosis and surgical diseases in patients more than 65 years old who present to the emergency department with nontraumatic abdominal pain of less than one week's duration, and to determine the ED staff's ability to diagnose and triage elderly patients with acute abdominal pain. DESIGN: A 12-month retrospective review of all elderly patients who presented to the ED with acute, nontraumatic abdominal pain. SETTING: A regional trauma center serving a predominately rural population in the Midwest. The ED has 55,000 patient visits yearly. MEASUREMENTS AND MAIN RESULTS: Of the 127 patients enrolled, 30 (24%) had no specific diagnosis made in the ED. Biliary tract disease (12%) and small bowel obstruction (12%) were the two most common specific diagnoses. Overall, 53 patients (42%) required surgery, usually during the initial hospitalization. In four cases, the postoperative diagnosis differed significantly from the ED diagnosis. Of the 74 patients (58%) who did not undergo surgery, 51 had follow-up information available. In 14 patients, the follow-up diagnosis differed from the original diagnosis, but most of these changes did not appreciably alter the treatment and outcome. CONCLUSIONS: The incidence of surgical disease is high in elderly patients with acute abdominal pain, and ED staff are able to diagnose and triage these patients accurately. PMID- 2240750 TI - Buffered versus plain lidocaine as a local anesthetic for simple laceration repair. AB - STUDY OBJECTIVE: Buffered lidocaine was compared with plain lidocaine as a local anesthetic for simple lacerations. DESIGN: Randomized, double-blind, prospective clinical trial. SETTING: Urban emergency department. TYPE OF PARTICIPANTS: Ninety one adult patients with simple linear lacerations were enrolled. Patients with allergy to lidocaine and patients with an abnormal mental status were excluded. INTERVENTIONS: Each wound edge was anesthetized with either plain or buffered lidocaine using a randomized, double-blind protocol. The pain of infiltration was measured with a previously validated visual analog pain scale. MEASUREMENTS AND MAIN RESULTS: Analysis of pooled data and paired data (using patients as their own controls) revealed that infiltrating buffered lidocaine was significantly less painful than plain lidocaine (P = .03 and P = .02, respectively). There was no significant difference in the anesthetic effectiveness of the two agents during suturing. CONCLUSION: Buffered lidocaine is preferable to plain lidocaine as a local anesthetic agent for the repair of simple lacerations. PMID- 2240751 TI - Submersion in The Netherlands: prognostic indicators and results of resuscitation. AB - STUDY OBJECTIVES: To analyze prognostic indicators and the outcome of resuscitation in submersion victims (drowning and near drowning). DESIGN: Retrospective study. SETTING: Intensive and Respiratory Care Unit. Between January 1, 1979, and December 31, 1985, 87 submersion victims were admitted. The files of 83 victims were available for statistical analysis. There were 66 male victims and 17 female victims; the average age was 31.4 +/- 25.8 years. There were ten salt water and 73 fresh water submersions. MEASUREMENTS AND MAIN RESULTS: Predictors for better survival potentials were a young age, submersion of less than ten minutes, no signs of aspiration, and a central body temperature of less than 35 C at admission. We did not detect factors that accelerated a decrease in core body temperature at admission and assume that lethal hypoxia had preceded protective hypothermia in our submersion victims. The Orlowski score had a predictive value but at the same time we found nonindependent indicators in this score. Neurologic outcome in our patients, who were not treated according to a brain protection protocol, was not worse than the outcome published by authors who have used such a protocol. Thirty-three percent of the victims with a cardioventilatory arrest (15) and all victims with a ventilatory arrest (11) survived resuscitation and were discharged. Five nonarrest victims died due to late complications. CONCLUSION: This study shows that no indicator at the rescue site and in the hospital is absolutely reliable with respect to death or survival. PMID- 2240753 TI - The trauma triage rule: a new, resource-based approach to the prehospital identification of major trauma victims. AB - STUDY OBJECTIVE: To develop a new trauma decision rule. DESIGN: Retrospective clinical review. SETTING: Level I trauma center. TYPE OF PARTICIPANTS: 1,004 injured adults. MEASUREMENTS AND MAIN RESULTS: A new trauma decision rule was derived from 1,004 injured adult patients using a new operational definition of major trauma. The rule, termed the Trauma Triage Rule, defines a major trauma victim as any injured adult patient whose systolic blood pressure is less than 85 mm Hg; whose motor component of the Glasgow Coma Score is less than 5; or who has sustained penetrating trauma of the head, neck, or trunk. Using the operational definition of major trauma, the rule had a sensitivity of 92% and a specificity of 92% when tested on the 1,004-patient cohort. CONCLUSION: The Trauma Triage Rule may significantly reduce overtriage while only minimally increasing undertriage. This approach must be validated prospectively before it can be used in the prehospital setting. PMID- 2240752 TI - The lack of full correlation between the Injury Severity Score and the resource needs of injured patients. AB - STUDY OBJECTIVE: To determine whether the Injury Severity Score (ISS) correlates with the resource requirements of severely injured patients by studying the association of the ISS with three major interventions (fluid resuscitation, invasive central nervous system monitoring, and acute operative repair) trauma centers routinely provide severely injured patients. DESIGN: Retrospective clinical review. SETTING: Level I trauma center. TYPE OF PARTICIPANTS: Eight hundred fourteen adult injured patients. MEASUREMENTS AND MAIN RESULTS: When an ISS of more than 9 was used as the definition of major trauma, the ISS undercorrelated 11% of the time with the need for any one procedure. When an ISS of more than 14 was used as the definition, it undercorrelated 20% of the time. CONCLUSION: The ISS may not be completely correlated with the resource requirements of injured patients and should not be used as the sole means by which to define major injury. PMID- 2240754 TI - Prehospital administration of inhaled metaproterenol. AB - STUDY OBJECTIVES: We conducted a study of the prehospital use of inhaled metaproterenol. DESIGN, SETTING, TYPE OF PARTICIPANTS, AND INTERVENTIONS: Advanced life support (ALS) providers were trained with a standardized curriculum to identify patients likely to benefit from prehospital inhaled metaproterenol administration. Unit doses of metaproterenol were used in a small-volume nebulizer. We prospectively included 122 patients in an initial study (71 men; age, 63 +/- 19 years) to evaluate the safety and effectiveness of metaproterenol in the field, and 150 patients (including the original 122) in an additional study to evaluate patient selection criteria. MEASUREMENTS AND MAIN RESULTS: The treatments resulted in an increase in peak flows, a decrease in respiratory rates, and no change in heart rates. In 62% of patients, the increase in peak flow exceeded 15%. Wheezing improved in 59% of the patients, worsened in 4%, and did not change in the remainder. Air entry by auscultation improved subjectively in 59% of patients. Mild tremor occurred in 8% of patients, moderate tremor occurred in 1%, and no tremor occurred in the remainder. Significant dysrhythmias did not occur. CONCLUSIONS: ALS providers correctly identified patients for this therapy. No technical problems were encountered in the field with this treatment approach. We conclude that ALS providers can be taught to identify patients likely to benefit from inhaled metaproterenol, that inhaled metaproterenol can be administered in the field, and that metaproterenol is both safe and effective when used in the prehospital setting. PMID- 2240755 TI - Geriatric injury: an analysis of prehospital demographics, mechanisms, and patterns. AB - STUDY OBJECTIVE: To evaluate emergency medical services (EMS) system use, injury mechanisms, and prehospital assessments among elderly victims of trauma. DESIGN: We analyzed all prehospital data for injuries among patients 70 years old or older for whom 911 EMS dispatch was requested in a medium-sized metropolitan area during a 12-month period. RESULTS: A total of 1,154 cases occurred (women, 65.1%), which represented 30.3% of all 911 dispatches involving elderly patients. Injury mechanisms were fall (60.7%), motor vehicle accident (MVA; 21.5%), fight (2.4%), accidental poisoning (2.3%), and choking (2.1%). Persons in their 90s had a lower frequency of MVAs (3.4%) than did younger patients (23.0%) (P less than .005). The most frequent injuries determined by prehospital assessment were head or face (25.1%), upper extremity (17.2%), hip (14.5%), lower extremity (13.8%), back (9.8%), and chest or abdomen (5.0%). The frequency of serious neurologic injuries was less for falls or MVAs than for other mechanisms (P less than .005). Suspected hip (P less than .001) and pelvic (P less than .005) injuries occurred more frequently during falls than during other mechanisms of injury, whereas back injuries occurred most frequently in MVAs (P less than .001). Seventy-one fall victims (10.1%) had suspected medical causes of their fall. Twelve patients (1.0%) were in cardiac arrest. CONCLUSION: We report injury patterns and mechanisms among elderly victims of trauma presenting to an EMS system. A knowledge of these patterns will be useful to emergency physicians and EMS administrators. PMID- 2240756 TI - Neurologic complications of cocaine abuse. AB - The neurologic complications of cocaine toxicity are responsible for a major portion of the morbidity and mortality associated with cocaine. Most of the complications appear to be related to the hyperadrenergic state induced by cocaine and may be treated symptomatically. Diazepam is the most effective drug for cocaine-induced seizures. PMID- 2240757 TI - Atypical presentation of pulmonary embolism. AB - Today we have discussed an interesting patient with an atypical presentation of pulmonary embolism. We have outlined a suggested algorithm to aid in the diagnosis and management of this disease. References 8 through 24 in the reference section are suggested readings that offer further insight into the diagnosis and management of this entity. PMID- 2240758 TI - Refusal of care and discharging 'difficult' patients from the emergency department. AB - Patients generally have the right to refuse medical care, a right based on certain legal precedents. Its application in the emergency department leads to difficult decisions for the emergency physician. A model that allows the emergency physician to determine the capacity of a patient to refuse care is presented. Certain types of patients regularly present problems in their treatment. These include psychiatric patients, narcotics abusers, alcoholics, "street people," and some patients with migraine headaches. They represent some of our most difficult decisions because the treatment required for the patient is often clear and the patient refuses care or demands inappropriate care. PMID- 2240759 TI - Occipital condyle fracture presenting as retropharyngeal hematoma. AB - Reported is the case of a 30-year-old male motorcycle accident victim who was found on plain cervical-spine radiography to have prevertebral soft-tissue swelling. Although subsequent computed tomography demonstrated no cervical-spine fracture, it did reveal a fracture of one occipital condyle. The mechanism, diagnosis, and treatment of occipital condyle fractures are reviewed, as is the ligamentous and fascial anatomy of the cervicocranium. Dissection of fracture hematoma inferiorly along vertically oriented tissue planes is hypothesized as the pathogenesis of our patient's retropharyngeal hematoma. In addition to being a sign of potential cervical-spine injury, post-traumatic prevertebral soft tissue swelling may also indicate occipital condyle fracture. To avoid overlooking such fractures, computed tomography undertaken to investigate upper cervical-spine prevertebral soft-tissue swelling should always include slices up to the level of the basal skull so as to visualize the condyles. PMID- 2240760 TI - Chylous drainage from a stab wound to the neck. AB - A 24-year-old man was assaulted and sustained a stab wound to the left lower neck. When he arrived at the emergency department, he was hemodynamically stable. Although the wound had penetrated the platysma, on initial evaluation the patient did not appear to have sustained significant injury. Closer examination of the wound revealed chylous drainage, indicating injury to the cervical portion of the thoracic duct. The patient was taken to the operating room for exploration of the wound, during which an injury to the left internal jugular vein was identified and repaired. The thoracic duct, which had been severed, was ligated. The remainder of the patient's hospital course was unremarkable. The consistent association between penetrating injury to the cervical portion of the thoracic duct and injury to neighboring vascular structures is discussed. PMID- 2240761 TI - Erythromycin failure with subsequent Pasteurella multocida meningitis and septic arthritis in a cat-bite victim. AB - We report the case of a 75-year-old woman who developed Pasteurella multocida meningitis and septic arthritis while being treated for a cat-bite wound infection with erythromycin. Review of the literature revealed that erythromycin has poor in vitro activity against this bacterium and has been associated with serious clinical failures. We recommend that erythromycin not be prescribed for empiric therapy of established animal-bite infections. Suggestions for optimal empiric therapy of animal-bite infections and the differential diagnosis of severe cat-bite-associated sepsis are discussed. PMID- 2240762 TI - Introduction to biostatistics: Part 6, Correlation and regression. AB - Correlation and regression analysis are applied to data to define and quantify the relationship between two variables. Correlation analysis is used to estimate the strength of a relationship between two variables. The correlation coefficient r is a dimensionless number ranging from -1 to +1. A value of -1 signifies a perfect negative, or indirect (inverse) relationship. A value of +1 signifies a perfect positive, or direct relationship. The r can be calculated as the Pearson product r, using normally distributed interval or ratio data, or as the Spearman rank r, using non-normally distributed data that are not interval or ratio in nature. Linear regression analysis results in the formation of an equation of a line (Y = mX + b), which mathematically describes the line of best fit for a data relationship between X and Y variables. This equation can then be used to predict additional dependent variable values (Y), based on the value or the independent variable X, the slope m, and the Y-intercept b. Interpretation of the correlation coefficient r involves use of r2, which implies the degree of variability of Y due to X. Tests of significance for linear regression are similar conceptually to significance testing using analysis of variance. Multiple correlation and regression, more complex analytical methods that define relationships between three or more variables, are not covered in this article. Closing comments for this final installment of this introduction to biostatistics series are presented. PMID- 2240763 TI - The need for ALS in urban and suburban EMS systems. PMID- 2240764 TI - What is 'major trauma?'. PMID- 2240765 TI - 'Trigger diagnoses'. PMID- 2240766 TI - 'Ideal' standards for pediatric EDs. PMID- 2240767 TI - Sludge/sluice. PMID- 2240769 TI - Use of the dot enzyme-linked immunosorbent assay with isolated Anaplasma marginale initial bodies for serodiagnosis of anaplasmosis in cattle. AB - Isolated Anaplasma marginale initial bodies were successfully used in a dot ELISA for rapid detection of antibodies to Anaplasma organisms. The enzyme immunoassay used only 25 ng of antigen dotted onto nitrocellulose disks. Antigen-antibody complexes were detected by use of alkaline phosphatase-conjugated protein A, and reactions were read visually after addition of a precipitable, chromogenic substrate. The test allowed the processing of multiple sera, either for screening or for titer determination, in less than 3 hours and was found to be as sensitive as the indirect fluorescent antibody test. The overall performance of the dot ELISA, using isolated A marginale initial bodies, for 580 bovine serum samples was as follows: sensitivity, 93%; specificity, 96%; and predictive value, 95%. Cross-reactivity was not observed with sera positive to Babesia bovis and B bigemina, Trypanosoma vivax, or common bacteria or viruses infecting cattle. The antigen dotted onto nitrocellulose disks was stable when stored at -20, 4, or 25 C. Compared with the indirect fluorescent antibody test, the dot ELISA allowed easier, faster, and more objective interpretation of results. Its simplicity and low cost combined with high sensitivity and specificity indicate that this assay could effectively replace serologic assays currently used for diagnosis of anaplasmosis in cattle. PMID- 2240768 TI - Visual-evoked potentials and electroretinograms in ruminants with thiamine responsive polioencephalomalacia or suspected listeriosis. AB - Electrodiagnostic visual testing (electroretinogram [ERG] and visual-evoked potential [VEP]) was performed on 5 ruminants (3 lambs, 1 kid, and 1 steer) with thiamine-responsive polioencephalomalacia (PEM) and on 2 sheep with listeriosis. The lambs and kid had typical clinical signs of PEM, especially blindness. In these animals, the ERG was normal but the VEP was abnormal. Follow-up recordings in the kid and 1 lamb indicated an improvement in VEP recordings accompanying a gradual return of vision after thiamine treatment. Possible subtle changes in VEP peak latencies could not be assessed because of lack of normative VEP data for sheep and goats. All animals had complete return of vision (owner-assessed). The steer did not have signs of blindness, and the ERG and VEP were normal. Changes in VEP accompanying permanent PEM blindness are not known. One sheep with suspected listeriosis had lack of menace response and palpebral and corneal reflexes, but had intact vision. The ERG and VEP were normal. The second sheep with suspected listeriosis had intact menace response and vision, but became acutely blind and died; the ERG was normal, but VEP amplitudes were depressed. PMID- 2240770 TI - Ultrasonographic examination of the liver in cows. AB - The size of the liver, as well as the situation and diameter of vessels in cattle were determined by use of ultrasonography. Ultrasonographic examinations of the liver were performed on 10 cows 10 times within 2 weeks, using a 3.5-MHz linear transducer on the right side in the 12th, 11th, and 10th intercostal spaces. Dorsal and ventral margin of the liver as well as localization and diameter of the caudal vena cava and the portal vein were determined in each intercostal space. Furthermore, the angle of the liver in the ventral area between the visceral surface and the diaphragmatic surface, the dorsal margin, and the circumference of the gall bladder were determined. The ultrasonographic values of liver size and localization in healthy cows can be used as reference values for the diagnosis of changes in liver size attributable to illness. PMID- 2240771 TI - Use of inflammatory cell activities in bovine milk to diagnose mastitis. AB - The activity of leukocytes, determined by chemiluminescence (CL) emission, was compared with the somatic cell count (SCC) in 4,883 quarter-milk samples from 132 dairy cows. The presence of bacteria was determined by bacteriologic culture of samples in which SCC and CL were high. Chemiluminescence was measured with an automated illuminometer system at 37 C after separating the leukocytes from milk by allowing them to adhere to cotton-wool swabs. Chemiluminescence emission was induced by opsonized zymosan and enhanced by luminol. After luminol and zymosan were added to the measuring vials containing the swabs, CL emission increased rapidly, reaching its maximum usually at about 15 minutes of reaction time, and decreasing slowly thereafter. In general, good correlation was found between CL and SCC (r = 0.876; P less than or equal to 0.001; n = 4,883). Even milk samples with low SCC gave reliably measurable CL signals. Minor pathogens in the milk caused about a sevenfold increase in both SCC and CL, whereas major pathogens caused 14- and 25-fold increases in SCC and CL, respectively. The diagnostic situation that requires both sensitivity and specificity to be at least 90% was attained only by the CL assay for major pathogens. These results suggest that the measurement of milk leukocyte activity by CL assay applies well to the diagnosis of mastitis, and has the potential to become a large-scale laboratory test, as well as a simple cowside test. PMID- 2240772 TI - Quantitative microanalysis of equine synovial fluid glycosaminoglycan concentration. AB - An alcian blue precipitation method for quantifying the hyaluronic acid (HA) and sulphated glycosaminoglycan concentration (SGAG) in solutions containing both compounds was assessed. The assay was found to be rapid and reliable in solutions containing 0 to 200 mg of HA/dl and 50 to 1,000 micrograms of SGAG/dl, and was not affected by the presence of protein, hemoglobin, or methemoglobin in concentrations normally found in synovial fluid. The HA and SGAG concentrations in intercarpal synovial fluid from 13 clinically normal and 11 arthritic horses were evaluated. A relationship was not found between the concentration of HA and SGAG and any other synovial fluid variable. The SGAG concentration was found to be markedly high in several of the synovial fluid samples from arthritic horses, but did not correlate with the degree of articular cartilage erosion. PMID- 2240773 TI - Comparison of two antigens for use in an enzyme-linked immunosorbent assay to detect African swine fever antibody. AB - Two African swine fever virus (ASFV) antigens were tested for use in an ELISA to detect antibody to ASFV. Antigens used were the cytoplasmic soluble fraction (CS P) of infected cells grown in the presence of porcine serum and the semipurified viral structural protein VP73 (SVP73). Both antigens were tested by ELISA against 72 sera obtained during several ASF field episodes and from ASFV-inapparent carriers. Of the 72 sera, only 2.8% has positive results by ELISA against CS-P antigen; 60% of positive-reacting sera (to both antigens) had higher ELISA values when the CS-P antigen was used. Samples (with positive results) that reacted only to CS-P antigen had results confirmed by immunoblot analysis. Such sera reacted against ASFV-infection proteins IP25, IP25.5, and IP30, but not against IP73. In time-course experiments to detect appearance of ASFV-antibodies in infected miniature pigs, antibodies were detected by immunoblot analysis on postinoculation day (PID) 8. At that time, only the polypeptides IP25, IP25.5 IP30, and IP31 were recognized; IP73 and IP12 were first detected 3 and 4 days later, respectively. In the same experiments, ASFV antibodies were detected by ELISA, using CS-P or SVP73 antigens, on PID 7 and 9, respectively. These results could explain the percentage of sera not having positive results by ELISA using SVP73 antigen, if the sera were obtained from ASFV-infected pigs during the first days of infection before induction of antibody response against the IP73 protein. This feature makes the use of CS-P antigen advantageous in early serologic detection of ASFV-infected pigs. PMID- 2240774 TI - Procollagen type-III aminoterminal peptide in serum and synovial fluid of dogs with hip dysplasia and coxarthrosis. AB - Hip dysplasia is an affection of the coxofemoral joint that progresses until stabilization is caused by fibrosis and osteoarthritic changes. This stabilization process can be examined by clinical and radiographic methods. The capability of evaluating the procollagen concentrations in liquids, such as serum and synovial fluid, has further offered the basis for an objective biochemical evaluation of the stabilization process. Our study was performed to evaluate whether determination of procollagen concentrations was suitable for the use in practice. The procollagen type-III aminoterminal peptide (P-III-NP) concentration was measured in serum and in synovial fluid from coxofemoral joints in 20 dogs. Dogs were grouped on the basis of evidence of dysplasia and osteoarthritic changes of the hip: (1) a control group of 6 dogs without clinical or radiographic signs of hip dysplasia, and (2) dysplastic group of 14 dogs, which was further grouped with respect to the coxofemoral joint laxity, as determined by the Ortolani test. Synovial fluid concentration of P-III-NP was significantly (P less than 0.05) higher in fluid from dysplastic joints than in fluid from normal joints. Serum concentrations of P-III-NP were significantly (P less than 0.05) higher in dogs in which results of the Ortolani test were positive. PMID- 2240775 TI - Evaluation of three applanation tonometers in dogs. AB - The Mackay-Marg, Tono-Pen, and Challenger applanation tonometers were evaluated in vivo in 12 clinically normal eyes of 6 dogs. Tonometric measures of intraocular pressure (IOP) were compared with closed manometric IOP measurements from the anterior chamber of anesthetized dogs. The tonometers were evaluated at IOP that ranged from 5 to 100 mm of Hg. The Mackay-Marg tonometer was the most reliable instrument when evaluated at IOP from 5 to 100 mm of Hg (r2 = 0.996) and from 10 to 30 mm of Hg (r2 = 0.962). The Tono-Pen tonometer was also reliable (r2 = 0.967) over the range of IOP, but consistently overestimated IOP at lower pressures and underestimated IOP at higher pressures. The Mackay-Marg and Tono Pen measurements were essentially linear. When evaluated from 10 to 30 mm of Hg, r2 was 0.828 for the Tono-Pen tonometer. The Challenger tonometer, although reliable over the full range of IOP (r2 = 0.965), proved to be less accurate, as indicated by lack of a good linear equation. PMID- 2240776 TI - Physiologic and body composition changes in feeder pigs under simulated marketing conditions. AB - Two experiments were conducted to determine changes in body composition and various physiologic variables in feeder pigs under simulated marketing conditions. In the first experiment, pigs were assigned to 1 of 4 treatment groups for 48 hours: (1) no water and feed; (2) water ad libitum, no feed; (3) no water, feed ad libitum; or (4) water and feed ad libitum. During a 48-hour recovery period, all pigs were allowed feed and water ad libitum. Plasma triiodothyronine decreased (P less than 0.01) within the first 24 hours in groups 1 and -2 pigs, but increased (P less than 0.01) within the first 6 hours of the recovery period. The circadian rhythm of plasma cortisol was disrupted in groups 1 and -3 pigs and during recovery in group-1 pigs. Packed cell volume increased (P less than 0.05) in groups-1 and -3 pigs and returned to initial values within the first 24 hours of the recovery period. In the second experiment, body composition was estimated by the 40K technique for fat-free body mass, percentage of nitrogen, and percentage of fat. Body composition was determined before and after pigs were allotted to 1 of 2 groups for 48 hours: group-1 pigs were given feed and water ad libitum and group-2 pigs were not given feed and water. Group-1 pigs gained 2.2 kg of body weight (P less than 0.01), 0.6% fat (P less than 0.01), 0.7 kg of fat-free body mass, and 0.02% nitrogen (P greater than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240777 TI - Lack of formyl-methionyl-leucyl-phenylalanine receptors on porcine neutrophils. AB - The response of blood neutrophils to the chemotactic peptide formyl-methyl-leucyl phenylalanine varies among species. Our results indicate that this peptide does not activate the respiratory burst of porcine neutrophils. Specifically, concentrations less than or equal to 10(-6) M did not cause production of either superoxide or hydrogen peroxide. Studies designed to delineate the biochemical deficit responsible for these results indicated that these cells do not express specific chemotactic peptide receptors on the external surface of the plasma membrane. Although these data do not rule out the possibility that internal stores of chemotactic peptide receptor exist, attempts to induce expression of the receptor by priming the cells with either lipopolysaccharide or calcium ionophore were unsuccessful. PMID- 2240779 TI - Retrograde flow of spermatozoa into the urinary bladder of dogs during ejaculation or after sedation with xylazine. AB - Retrograde flow of spermatozoa into the urinary bladder of dogs during ejaculation or after administration of xylazine was examined. In experiment 1, the mean (+/- SD) spermatozoal concentration in urine collected by cystocentesis before ejaculation was 0.322 +/- 0.645 X 10(6)/ml. After ejaculation, motile spermatozoa were present in the urine collected by cystocentesis from 12 of 15 dogs, and the concentration of spermatozoa in the urine (5.139 +/- 7.014 X 10(6)/ml) was higher (P less than 0.025) than the concentration in the urine collected before ejaculation. The percentage of the total number of spermatozoa that were displaced during ejaculation and flowed into the urinary bladder (retrograde flow) ranged from 0 to 99.75% (24.67 +/- 33.98%). In experiments 2 and 3, administration of xylazine to sexually rested dogs induced retrograde flow of spermatozoa into the urinary bladder. In experiment 2, all dogs had spermatozoa in urine collected after xylazine administration, with motile spermatozoa present in the urine from 9 of 10 dogs. In experiment 3, urine collected from dogs before administration of xylazine was azoospermic or contained few, nonmotile spermatozoa (0.063 +/- 0.135 X 10(6)/ml), whereas urine collected after administration of xylazine had more (P less than 0.025) and motile spermatozoa (3.717 +/- 4.273 X 10(6)/ml). In experiment 4, administration of xylazine to dogs after ejaculation did not increase the concentration of spermatozoa in the urine. Results indicate that spermatozoa flow into the urinary bladder of dogs during ejaculation or after administration of xylazine to sexually rested dogs. PMID- 2240778 TI - Postadulticide pulmonary hypertension of canine heartworm disease: successful treatment with oxygen and failure of antihistamines. AB - Postadulticide pulmonary hypertension mechanisms and treatment with antihistamines and supplemental oxygen were studied in eight dogs with heartworm disease. To ensure severe postadulticide thromboembolism, additional heartworms (either 20 or 40 into 4 dogs each) were transplanted into naturally infected dogs before thiacetarsamide treatment. During pentobarbital anesthesia, 2 pulmonary hemodynamic studies were conducted on each dog with a sequence of baseline, hypoxia with FlO2 = 10%, hyperoxia with FlO2 = 100%, a second baseline, treatment with either diphenhydramine (D) or cimetidine (C), and another hypoxia. All dogs were pulmonary hypertensive, with each dog having a mean pulmonary arterial pressure (PPA) greater than 20 mm of Hg. Mean PPA increased from baseline conditions (25.0 +/- 4.5 SD for D and 24.3 +/- 4.4 for C) to hypoxia (28.5 +/- 4.7 for D and 28.4 +/- 3.7 for C), and decreased during hyperoxia (16.9 +/- 3.0 for D and 17.4 +/- 3.0 for C), respectively. Neither antihistamine reduced PPA at normoxia. The degree of pulmonary hypertension when breathing room air increased even more during hypoxia, and this increase was not attenuated by either antihistamine. Histamine did not appear to mediate pulmonary hypertension during postadulticide thromboembolism, nor to modify the hypoxia-mediated pulmonary hypertension at this disease stage. Because baseline PO2 was low (66.6 +/- 11.7 mm of Hg for D and 69.4 +/- 14.2 for C) and because PPA decreased during administration of oxygen, the pulmonary hypertension was mostly hypoxia-induced. In addition to the arterial lesions, much of the pulmonary hypertensive mechanism was an active and reversible vasoconstriction in response to hypoxia caused by the secondary lung disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240780 TI - Changes in oscillatory potentials in the canine electroretinogram during dark adaptation. AB - Oscillatory potentials (OP) and electroretinograms (ERG) were recorded from clinically normal dogs after 5, 10, 15, 20, 30, 40, 50, and 60 minutes of dark adaptation. At the end of the adaptation period, OP were characterized by 5 distinct positive peaks, O1 through O5, with mean latencies of 14.46, 20.24, 27.38, 35.31, and 44.85 ms, respectively, and with mean amplitudes ranging from 7.20 to 34.84 microV. After 60 minutes of dark adaptation, the ERG had a mean a wave latency of 12.03 ms and a mean b-wave amplitude of 109.29 microV. Peaks O3 and O4, which partially mask the summit of the b-wave, had mean latencies of 28.66 and 36.83 ms, respectively. The mean amplitude of the b-wave measured to the peak of O3 was 240.06 microV and 230.73 microV when measured to peak O4. Changes in the OP during dark adaptation consisted of significant (P less than 0.05) increases in the latencies of O1, O2, and O3, and significant increases in the amplitudes of O1, O3, O4, and O5. Concurrent ERG changes consisted of significant increases in the amplitudes of the a-wave and b-wave measured from O3 and O4, and significant increases in the latencies of peaks O3 and O4 on the b wave. PMID- 2240781 TI - Correlation of sensory electroneurographic recordings and myelinated fiber diameters of the superficial peroneal nerve of dogs. AB - The compound nerve action potential (CNAP) of the superficial peroneal nerve of dogs was investigated to determine: (1) the influence of the stimulation technique on the configuration of the CNAP, with particular attention to late components; (2) the fiber diameter (FD) distribution; and (3) the relationship between FD distribution and CNAP configuration, by reconstruction of CNAP made on the basis of FD distributions. The CNAP were evoked in 9 dogs under halothane anesthesia by 2 stimulation methods: percutaneous needle electrode stimulation and direct stimulation of the exposed superficial peroneal nerve. Recordings were made with percutaneous needle electrodes. Full nerve cross sections of 7 superficial peroneal nerves were prepared for FD morphometric analysis. Reconstruction of CNAP were made on the basis of the FD distributions. Late components of the CNAP could be evoked with either stimulation method, but only with a stimulus intensity of 3 to 5 times maximal for the main (early) component of the CNAP. The FD histograms of 7 analyzed nerves had bimodal distribution. In 5 nerves, peaks were at 4.2 to 4.5 microns and 9.0 to 10.0 microns, with 60% of the fibers in the small-diameter group. In 2 nerves with lower maximal conduction velocities, peaks were shifted toward smaller values. The CNAP reconstructions made by use of FD data closely resembled actual recordings when a fifth-order polynomial function was applied to the relationship between nerve conduction velocity and FD. Reconstructions made by use of 1 or 2 linear functions did not accurately resemble actual recordings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240783 TI - Flow cytofluorometric studies on the alteration of leukocyte populations in blood and milk during endotoxin-induced mastitis in cows. AB - Alterations in the various leukocyte populations in milk, blood, and mammary lymph were studied by use of the flow cytometric method during acute mastitis episodes induced by endotoxin infusion (50 micrograms of lipopolysaccharide of Salmonella typhimurium SH 4809) via the teat canal. Lymph samples were collected via a semipermanent catheter from an afferent duct to the supramammary lymph node. Milk somatic cell count increased at 4 hours after infusion of endotoxin. Neutrophils were the predominant cell population for up to 59 hours after infusion. Numbers of lymphocytes and monocytes-macrophages in milk also increased after the endotoxin infusion. The total cell count in milk started to decrease during the third postinfusion day and returned to preinfusion values during the fourth day. Lymphocyte numbers remained high for about 1 week after the infusion, and lymphocytes were the predominant cell population between postinfusion days 4 and 8. Total blood leukocyte count decreased during the first 6 hours after infusion, followed by an increase until postinfusion hour 31. The proportion of neutrophils in blood increased during the first day, whereas that of lymphocytes decreased. Lymph flow rate and leukocyte numbers in lymph increased after endotoxin infusion. The proportion of neutrophils in the lymph increased during the first 6 hours, whereas that of lymphocytes decreased. After postinfusion hour 6, the inverse course of events was seen. PMID- 2240782 TI - Systemic and secretory antibody responses to sequential bovine respiratory syncytial virus infections in vaccinated and nonvaccinated calves. AB - To investigate the influence of humoral immunity on the severity of disease caused by infection with bovine respiratory syncytial virus (BRSV), an experimentally induced infection study was performed on vaccinated and nonvaccinated calves. Fifteen weanling calves were allotted to 3 groups: 1 group of 6 calves was exposed to 2 live virus aerosols, 35 days apart; another group of 6 calves was vaccinated prior to the same aerosol exposures; and the remaining 3 calves served as controls. Clinical signs of infection were converted to a numerical score for evaluating disease severity. For 14 days after each virus exposure, BRSV-specific IgG and IgM concentrations in serum and BRSV-specific IgA concentration in nasopharyngeal exudate and lung lavage fluid were measured by ELISA. Serum BRSV-specific IgG and IgM and secretory BRSV-specific IgA concentrations did not correlate with disease sign expression. There was a strong correlation between viral isolation and disease scores. Vaccination prior to virus exposure appeared to have little or no effect on severity of the disease, but it did appear to affect disease persistence. Findings indicate that the immunoglobulins evaluated may be primarily protective in nature and do not contribute to disease severity. PMID- 2240784 TI - Production and partial characterization of monoclonal antibodies to the neotype strain of Mycobacterium bovis. AB - Six monoclonal antibodies (MAB) to virulent Mycobacterium bovis ATCC 19210 were produced, using a suspension of heat-inactivated whole cells. Immunoglobulin isotype for MAB VMB6, VMB73, and VMB93 was IgG1, and for VMB31, VMB99, and VMB119, it was IgG2a. Monoclonal antibodies were examined for cross-reactivity to M tuberculosis, M kansasii, M fortuitum, M paratuberculosis, M avium serovars 1, 2, 4, 8, and 10, M chelonei, M phlei, M scrofulaceum, M smegmatis, Nocardia asteroides, and Rhodococcus equi. Monoclonal antibodies could be grouped on the basis of binding activity by ELISA and immunoblot analysis, in which MAB VMB6, VMB31, and VMB119 had binding activity to M bovis; MAB VMB93 and VMB99 detected M bovis and M tuberculosis antigens, and MAB VMB73 reacted with other mycobacterial species, as well as with N asteroides and R equi. Apparent molecular mass of antigens was 30 to 25 kilodaltons (kD) for VMB6, VMB31, and VMB119 and 63 kD for VMB93 and VMB99, and ranged from greater than 200 to 31 kD for VMB73, as estimated by immunoblot analysis. Monoclonal antibody binding activity to 18 field isolates of M bovis was evaluated, using ELISA. Each of 18 field isolates was detected, using MAB VMB6, VMB31, or VMB119; 10 isolates were detected, using MAB VMB93/VMB99, and 14 were detected by use of MAB VMB73. Use of MAB in ELISA failed to detect antigens from M bovis strain AN-5. PMID- 2240785 TI - Immune response to pulmonary injection of Pasteurella haemolytica-impregnated agar beads followed by transthoracic challenge exposure in goats. AB - A method of inducing Pasteurella haemolytica serotype 1 (Ph1) lung infection in goats, using low numbers of bacteria and without impairing host immunity, was developed. Two trials were conducted. Results of trial 1, using 10 principals (Ph1 agar beads) and 6 controls (agar beads alone), indicated that Ph1 organisms imbedded in agar beads could survive host lung defenses for 32 days. Results of trial 2 indicated that lung immunity in the inoculated goats (principals) was high and they were more protected than controls against a transthoracic challenge of Ph1 (1.18 x 10(7) colony-forming units) injected into a lung of each goat on posttreatment day 35. When comparing challenge-exposed principals with controls, the controls developed rectal temperatures above normal for a longer time, duration of anorexia was longer, and signs of depression were seen. The controls developed large areas of consolidated lung tissue, more Ph1 isolates were recovered from nasal turbinates and lung tissue, and higher Ph1 concentrations were found in the lungs. The serum Ph1 indirect hemagglutination antibody titers in the principals of both trials increased, compared with titers in controls. Principal goats in trial 2 had higher Ph1 indirect hemagglutination antibody titers after injection of Ph1-impregnated agar beads and less severe lung lesions after challenge exposure than did controls. The small pneumonic consolidated lesions in the principals, compared with extensive lesions in controls after Ph1 challenge exposure, indicated a high degree of immunity after exposure to Ph1 organisms imbedded in agar beads. PMID- 2240786 TI - Strategic use of anthelmintics to prevent parasitic gastroenteritis in cow-calf herds in California. AB - On the basis of the hypothesis that the peak numbers of infective nematode third stage larvae (L3) on herbage in winter months results from fall contamination of pastures, 2 methods to reduce fall contamination were tested. In trial 1, morantal sustained-release boluses were administered to 15 fall-calving cows on Sept 7, 1982. Fifteen untreated cows (controls) were placed on separate pastures. Numbers of L3 on herbage during the winter and spring were assessed by use of worm-free tracer calves. In trial 2, 19 cattle due to calve in the fall were administered 200 micrograms of invermectin/kg of body weight, SC, on Sept 2, 1983. Also, 17 cattle similarly were given a placebo injection and served as control animals. Treated cattle were placed on the pasture used by control cattle in trial 1 and control cattle on the pasture used by treated cattle in trial 1. Worm-free tracer calves were again used to assess numbers of L3 on herbage. In trial 1, tracer calves grazing the control animal pasture from January 14 to 28 acquired 37 times as many nematodes as did those grazing the treated animal pasture. In trial 2, the greatest difference observed was a 10-fold increase of nematodes in calves grazing control animal pastures, compared with worm numbers in tracer calves grazing the treated animal pasture. PMID- 2240787 TI - Effectiveness of arprinocid in the reduction of cryptosporidial activity in immunosuppressed rats. AB - Immunosuppressed rats inoculated with Cryptosporidium oocysts isolated from calves' feces were treated with arprinocid, 50 mg/kg of body weight/d. As determined from differences in the mean number of cryptosporidial developmental stages per villus in treated vs control rats, arprinocid had a substantial effect on cryptosporidial activity, which was parasitistatic instead of parasiticidal. Drug-ranging experiments indicated that arprinocid was effective at 50 and 25 mg/kg/d, but not at 12.5 mg/kg/d. These results suggest that further testing of arprinocid in different animal models, or in phase-I clinical trials, is warranted. PMID- 2240788 TI - Absorption kinetics of regular insulin in dogs with alloxan-induced diabetes mellitus. AB - The absorption kinetics of porcine regular insulin following IV, IM, and SC administration were evaluated in 10 dogs with alloxan-induced diabetes mellitus. Plasma immunoreactive insulin (IRI) concentrations were evaluated immediately prior to and at 10, 20, 30, 45, 60, 90, 120, 180, and 240 minutes following IV administration; and immediately prior to and every 30 minutes for 2 hours and then every hour for 6 hours following IM and SC administration of 0.55 U of porcine regular insulin/kg of body weight. Model-independent pharmacokinetic analysis was performed on each data set. Plasma IRI concentration declined rapidly after IV administration of regular insulin and then returned to baseline IRI concentration by 3.2 +/- 0.8 hours. The absorption kinetics following IV administration of regular insulin were similar to those found in earlier studies in healthy dogs and human beings. The IM and SC routes of regular insulin administration resulted in a pharmacologic concentration of IRI at 30 minutes. The peak mean (+/- SD) plasma IRI concentration was significantly (P less than 0.05) greater following SC administration than it was following IM administration of regular insulin (263 +/- 185 and 151 +/- 71 I microU/ml, respectively). The time of the peak plasma IRI concentration (68 +/- 31 minutes and 60 +/- 30 minutes) and the time to return to baseline plasma IRI concentration (5.8 +/- 1.2 hours and 5.8 +/- 1.3 hours) were not significantly different following SC and IM administration of regular insulin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240789 TI - Effect of gentamicin administration on the neuromuscular blockade induced by atracurium in cats. AB - Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered as an infusion to 8 anesthetized cats in which neuromuscular blockade was assessed, using the train-of-four response. Once 50% depression of the first-twitch (T1) response was achieved, the infusion was held constant for 60 minutes before being discontinued and the recovery time was determined. The time for recovery was recorded as the time for the train-of-four (T4 ratio) to increase from 50% to 75%. After recovery, atracurium infusion was reinstituted and the cats were again maintained for 60 minutes at 50% depression. A single bolus of gentamicin sulfate (2.0 mg/kg of body weight) was administered IV, and the infusion was continued for another 60 minutes before it was discontinued and the time for recovery was recorded. Within 1 minute of gentamicin administration, the mean +/- SD T1 response decreased from 49 +/- 5% to 33 +/- 8% of baseline and the T4 ratio decreased from 28 +/- 19% to 14 +/- 11%. Peak effect occurred at 5 minutes, with a T1 response of 29 +/- 6% of baseline and a T4 ratio of 13 +/- 12%. By 60 minutes after gentamicin administration, the T1 response had increased to 38 +/- 7% of baseline and the T4 ratio had increased to 21 +/- 13%. The time for recovery significantly (P less than 0.03) increased from 9.9 +/- 3.4 minutes during the control study to 18.1 +/- 10.7 minutes during the gentamicin study. In this study, gentamicin potentiated the neuromuscular blockade induced by atracurium and increased the recovery time. Residual blockade, observed after gentamicin administration was reversed with edrophonium. PMID- 2240790 TI - Effect of transport loading or noise on blood biochemical variables in calves. AB - The influence of 2 transport stressors (loading and noise) on several serum and plasma biochemical variables was studied in 4 calves. When calves were loaded and kept for 30 minutes on a motionless transport simulator or were exposed to the noise of the working simulator, increases in plasma epinephrine and serum cortisol and nonesterified fatty acids concentrations were similar to changes observed in calves subjected to simulated transport for 30 minutes. Results indicate that loading and noise have an important role in transport stress. PMID- 2240791 TI - Effects of tetracycline hydrochloride on pleurae in dogs with induced pleural effusion. AB - Pleural effusion was induced in 12 dogs by ligation of the cranial vena cava. Pleurodesis was attempted by injecting a solution of tetracycline hydrochloride into the pleural space of 8 dogs (4 dogs, 25 mg/kg of body weight; 4 dogs, 50 mg/kg) via bilateral thoracostomy tubes. In both groups, tetracycline was diluted in 40 ml of normal saline solution and 10 ml of 1% lidocaine before injection. Half of the solution (25 ml) was instilled in each hemithorax. Four control dogs were treated in the same manner with a solution of normal saline and lidocaine. Daily pleural fluid production was measured after the attempted pleurodesis. Thirty days after administration of the solution, each dog was euthanatized and necropsied. Surface area of pleural adhesions was measured. Tissues from regions of pleural adhesions and areas of parietal and visceral pleura not involved in adhesions were analyzed histologically. Formation of pleural fluid stopped in all but 1 control dog within 48 hours after injection of solution. This dog effused throughout the study. The resolution of effusion was not significantly (P less than 0.05) different between the tetracycline-treated dogs and the control group. Although diffuse pleural adhesions were not induced in any of the dogs, significantly (P less than 0.0027) more surface area of lung was adhered in dogs treated with the higher dose of tetracycline. PMID- 2240792 TI - Effects of treatment of growing swine with aflatoxin and T-2 toxin. AB - Effects of dietary aflatoxin (AF) and T-2 toxin, singly and in combination, were evaluated in growing crossbred (Yorkshire x Landrace x Hampshire) pigs. The experimental design consisted of 4 treatment groups of 6 barrows each fed diets containing 0 mg of AF and T-2/kg of feed (controls; group 1), 2.5 mg of AF/kg of feed (group 2), 10 mg of T-2/kg of feed (group 3), or 2.5 mg of AF plus 10 mg of T-2/kg of feed (AF + T-2; group 4) ad libitum for 28 days (7 to 11 weeks of age). Production performance, and serum biochemical, and hematologic evaluations were made weekly. Body weight and body weight gain were depressed by all toxin treatments, but the effect of AF and T-2 toxin in combination was less than additive. Liver and kidney weights, as a percentage of body weight, were increased by AF treatment, and heart weight, as a percentage of body weight, was increased by T-2 treatment. Treatment with T-2 toxin induced necrotizing contact dermatitis on the snout, buccal commissures, and prepuce. Consumption of AF resulted in increased serum activities of alkaline phosphatase, aspartate transaminase, cholinesterase, and gamma-glutamyltransferase, and decreased serum concentrations of urea nitrogen, cholesterol, albumin, total protein, calcium, potassium, magnesium, and phosphorus. Consumption of T-2 toxin resulted in increased serum triglyceride concentration and decreased serum iron concentration. Treatment with AF induced lower serum unsaturated iron-binding capacity and high RBC count, PCV, hemoglobin concentration, WBC count, and prothrombin time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240793 TI - Effect of endotoxin administration on equine digital hemodynamics and starling forces. AB - Using a pump-perfused extracorporeal isolated digital preparation, the effects of a 30-minute infusion of either saline solution (control) or endotoxin on equine digital hemodynamics and microvascular function were determined. Digital blood flow and arterial, venous, and capillary pressures were recorded at 15-minute intervals for 150 minutes. From these data, total vascular resistance and pre- and postcapillary resistances were calculated. Isogravimetric capillary filtration coefficient, vascular compliance, and the osmotic reflection coefficient were determined after the last hemodynamic measurements were taken. Changes in hemodynamic values of control equine digits were not observed. During the 120 minutes after infusion of endotoxin, digital blood flow decreased 43%, and total vascular resistance increased 89%. Precapillary resistance increased 122%, but postcapillary resistance did not change significantly. Changes in vascular compliance or the capillary filtration coefficient were not observed in response to either treatment. The osmotic reflection coefficient, an index of permeability, did not differ significantly between digits of the endotoxin treated and control groups. These data indicate that the increase in vascular resistance during endotoxemia may have been attributable to arterial/arteriolar constriction and that neither the permeability nor the surface area of the exchange vasculature within the digit was significantly affected by endotoxin. Although marked alterations in vascular function are seen after administration of endotoxin, these changes do not parallel those documented in association with experimentally induced laminitis. PMID- 2240794 TI - Plasma hormone concentrations after administration of dexamethasone during the middle of the luteal phase in cows. AB - The effect of glucocorticoids on gonadal steroid and gonadotropic hormone concentrations and subsequent follicular activity in cows undergoing normal estrous cycles was evaluated by administration of dexamethasone (DXM) during the middle of the luteal phase. Seven cows were given physiologic saline solution twice daily from day 13 to day 17 of the estrous cycle (control experiment). During the next estrous cycle, cows were administered DXM (2 mg, IM) twice daily on days 13 through 17. Plasma specimens obtained twice daily throughout the control and DXM-treatment cycles were assayed for progesterone and estradiol concentrations. The appearance of estrus after DXM treatment was delayed until days 23 to 25 in 3 cows and was not seen by day 35 in the other 4 cows, compared with mean (+/- SD) cycle length of 22.4 +/- 3.2 in cows during the control experiment. Progesterone concentration remained significantly (P less than 0.01) high on days 19 to 23, whereas estradiol values failed to increase (P less than 0.05) on days 19 and 20 after treatment with DXM. Blood samples were obtained at 15-minute intervals for 12 hours to compare (by analysis of covariance) the effect of DXM treatment on plasma hormone concentrations on day 15 of each cycle with those of day 10. Compared with values during the control experiment, a significant (P less than 0.05) decrease was observed in the size of the pulses of luteinizing hormone (LH) and estradiol, although the number of pulses of each hormone per 12 hours was not affected when cows were given DXM. Baseline concentrations of LH and estradiol were not altered by type of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240795 TI - Experimental model of hypochloremic metabolic alkalosis caused by diversion of abomasal outflow in sheep. AB - Hypochloremic metabolic alkalosis accompanied by hypokalemia and hyponatremia was induced experimentally in 7 adult sheep by diversion (loss) of gastric contents through an Ivan and Johnston cannula placed in the cranial part of the duodenum just distal to the pylorus. Cannula placement was easily accomplished, and cannulae were tolerated well by the sheep. Volume of effluent produced during the 60- to 120-hour period of diversion ranged from 7.7 to 14.9 L and tended to be greatest during the first 24 hours. All sheep became dehydrated, with mean PCV and plasma total protein concentration increases of 94.2 and 61.7%, respectively. Plasma chloride concentration decreased in linear fashion from a prediversion mean of 113 mEq/L (range, 111 to 117 mEq/L) to an end-point mean of 54 mEq/L (range, 45 to 65 mEq/L). Plasma sodium and potassium concentrations also decreased, though potassium concentration increased terminally. There were rapid increases in arterial blood pH and bicarbonate and base excess concentrations during the first 48 hours after diversion. However, during the final stages of diversion, sheep developed superimposed metabolic acidosis with increased plasma lactate concentration and high anion gap. PMID- 2240797 TI - Evoked potentials induced by transcranial stimulation in dogs. AB - Evoked potentials were induced by transcranial stimulation and recovered from the spinal cord, and the radial and sciatic nerves in six dogs. Stimulation was accomplished with an anode placed on the skin over the area of the motor cortex. Evoked potentials were recovered from the thoracic and lumbar spinal cord by electrodes placed transcutaneously in the ligamentum flavum. Evoked potentials were recovered from the radial and sciatic nerves by surgical exposure and electrodes placed in the perineurium. Signals from 100 repetitive stimuli were averaged and analyzed. Waveforms were analyzed for amplitude and latency. Conduction velocities were estimated from wave latencies and distance traveled. The technique allowed recovery of evoked potentials that had similar characteristics among all dogs. Conduction velocities of potentials recovered from the radial and sciatic nerves suggested stimulation of motor pathways; however, the exact origin and pathway of these waves is unknown. PMID- 2240796 TI - Renal net acid and electrolyte excretion in an experimental model of hypochloremic metabolic alkalosis in sheep. AB - Renal electrolyte and net acid excretion were characterized during generation and maintenance of hypochloremic metabolic alkalosis in a ruminant model. Two phases of renal response with regard to sodium and net acid excretion were documented. An initial decrease in net acid excretion was attributable to increase in bicarbonate excretion with associated increase in sodium excretion. As the metabolic disturbance became more advanced, a second phase of renal excretion was observed in which sodium and bicarbonate excretion were markedly decreased, leading to increase in net acid excretion and development of aciduria. Throughout the metabolic disturbance, chloride excretion was markedly decreased; potassium excretion also decreased. These changes were accompanied by increase in plasma renin and aldosterone concentrations. There was apparent failure to concentrate the urine optimally during the course of the metabolic disturbance, despite increasing plasma concentration of antidiuretic hormone. PMID- 2240798 TI - Maturational development of drug-metabolizing enzymes in sheep. AB - A qualitative and quantitative assessment was made of the development of hepatic drug-metabolizing enzymes (DME) in sheep as part of a study of the ability of the food-producing species to metabolize drugs. The following DME and components were measured in this study: cytochromes P-450 and b5 and NADPH and NADPH-dependent reductases associated with each of these cytochromes; cytochrome P-450-mediated reactions, including aniline and coumarin hydroxylases, aminopyrine N demethylase, and 7-ethoxycoumarin 0-deethylase; a uridine diphosphoglucuronic acid glucuronyl transferase with 4-methylumbelliferone as substrate; and glutathione-S-transferase with dinitrochlorobenzene and dichloronitrobenzene as substrates. Amounts or activities of most of these components and enzymes increased up to and beyond the time of weaning. Amount of cytochrome b5 and uridine diphosphoglucuronic acid transferase activity were not affected by age, whereas NADPH cytochrome c (P-450) reductase activity actually decreased after weaning. In some instances (eg, coumarin hydroxylase, cytochrome P-450, and dinitrochlorobenzene-glutathione-S-transferase), differences from preweaning DME values were observed only after sheep were greater than or equal to 6 months old. All other DME activities were definitely increased, compared with the values in lambs before weaning (0 to 12 weeks old). Approximately a third of the sheep studied had some type of clinical disease that might have affected the DME activities. Diseases were classified as sore mouth, pneumonia, foot rot, parasitism, and systemic bacterial infections. Except in a few instances, these diseases had minimal effect on DME activities measured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240799 TI - Effects of a specific thromboxane synthetase inhibitor on thromboxane generation and excretion in healthy dogs. AB - A specific thromboxane synthetase inhibitor, 3-methyl-2 (3-pyridyl)-1 indoleoctanoic acid (CGS 12970) was administered orally to 6 healthy adult Beagles at a dosage of 30 mg/kg of body weight. Blood generation of thromboxane B2 and urinary excretion of thromboxane B2 were measured before and after administration of CGS 12970. Although 97 +/- 0.4% inhibition of thromboxane B2 generation was observed within 2 hours after a single dose of CGS 12970 was administered orally, an effect on urinary excretion of thromboxane B2 was not observed. Additionally, oral administration of 30 mg/kg every 12 hours resulted in 80 +/- 14% inhibition of thromboxane B2 generation but had no effect on urinary thromboxane B2 excretion. PMID- 2240800 TI - Pharmacokinetics of single doses of digoxin administered intravenously to ducks, roosters, and turkeys. AB - A single dose of digoxin was injected, IV, into 5 mature male turkeys (0.066 mg/kg of body weight), 8 male ducks (0.066 mg/kg), and 6 roosters (0.33 mg/kg). Twenty-three serial venous blood samples were collected before (baseline) and after the administration of digoxin to turkeys, ducks, and roosters. Plasma concentrations of digoxin were determined in duplicate by a radioimmunoassay that was validated for avian species. The plasma concentrations were best fitted by a 3 (turkeys, ducks)- and 2 (roosters)-compartment open model, with first-order elimination from the central compartment. Significant (P less than 0.05) kinetic differences were determined among species. Mean half-life (t1/2) for ducks, roosters, and turkeys were 8.30 +/- 2.70 (mean +/- SD), 6.67 +/- 3.50, and 23.7 +/- 4.8 hours, respectively. The volume of distribution at steady state (Vss) was 14.7 +/- 2.9, 3.13 +/- 0.49, and 2.27 +/- 0.36 L/kg, and total body clearance (CL) of drug was 1.54 +/- 0.43, 0.461 +/- 0.187, and 0.136 +/- 0.022 L/h/kg for ducks, roosters, and turkeys, respectively. The mean residence time was 10.3 +/- 3.9, 8.37 +/- 4.97, and 16.8 +/- 2.2 hours, respectively. Volume of distribution at steady state and CL in ducks were several fold higher than that in turkeys. The terminal half-life of digoxin determined for ducks and roosters in this study was considerably shorter than those previously reported for several mammalian species. PMID- 2240801 TI - Pharmacokinetics of pipemidic acid in chickens after single intravenous and oral dosings. AB - The pharmacokinetics of pipemidic acid after 2 single doses were studied in broiler chickens. Chickens were given single IV and oral doses of 10 and 30 mg of pipemidic acid/kg of body weight. Blood samples were collected over 8 hours after each dose administration. High-pressure liquid chromatography with UV detection was used to determine concentrations in plasma of pipemidic acid. The plasma concentration-time curves after IV administration followed 2-compartment characteristics, rapid initial distribution phase, and a terminal elimination phase. The pharmacokinetic variables differed significantly between single doses of 10 and 30 mg of pipemidic acid/kg. Mean disposition variables were a half-life at alpha phase of 0.06 hours or 0.33 hours, a half-life at beta phase of 1.18 hours or 1.72 hours, a volume of distribution in the central compartment of 0.12 L/kg or 0.31 L/kg, a volume of distribution during the elimination beta phase of 1.64 L/kg or 1.05 L/kg, and a total plasma clearance of 0.97 L/h.kg or 0.41 L/h.kg, for the 10 or 30 mg/kg dose, respectively. After oral administration, the pipemidic acid plasma profile could be adequately described by a 1-compartment model. After the single oral doses of 10 and 30 mg of pipemidic acid/kg, pipemidic acid was absorbed rapidly (time to maximal concentration of 0.31 hours or 0.71 hours) and eliminated with a mean half-life of 0.86 hours or 0.61 hours, respectively. The bioavailability was 39% at 10 mg of pipemidic acid/kg and 61% at 30 mg of pipemidic acid/kg. PMID- 2240802 TI - Recombinant DNA probe detecting Eperythrozoon suis in swine blood. AB - A genomic library to Eperythrozoon suis DNA was constructed in lambda gt11, and from this library, E suis clone KSU-2 was identified as a potential diagnostic probe. In hybridization experiments that used 100-microliters samples of blood collected in chaotropic salt solutions, the KSU-2 probe hybridized strongly with purified E suis organisms and blood samples from splenectomized swine that were parasitized with E suis. However, the probe under stringent conditions did not give radiographic indications of hybridizing with equine blood DNA, bovine blood DNA infected with Anaplasma marginale, canine blood DNA infected with Ehrlichia canis, feline blood DNA infected with Haemobartonella felis, or uninfected swine blood DNA. PMID- 2240803 TI - Endomyocardial biopsy in cats. AB - A technique for transvenous endomyocardial biopsy of the right ventricle was developed and evaluated for safety and efficacy in anesthetized healthy cats positioned in left lateral recumbency. At least 6 endomyocardial biopsy specimens were obtained from the right ventricle or interventricular septum of 11 cats. In 4 cats, the right jugular vein was torn during attempts to pass the introducing catheter into the right ventricle; however, in only 1 cat did this preclude catheter passage. This cat's heart was biopsied via the left jugular vein. Except for damage to the jugular vein, complications were infrequent, and the biopsy procedure was well tolerated by all cats. PMID- 2240804 TI - Modified transvenous endomyocardial biopsy technique in dogs. AB - A technique for transvenous endomyocardial biopsy of the right ventricle was developed and evaluated for safety and efficacy in healthy dogs and dogs with dilated cardiomyopathy positioned in lateral recumbency. This technique allowed acquisition of multiple biopsy specimens from the right ventricle of each of 22 hemodynamically normal dogs and 40 of 42 dogs with congestive heart failure. In 2 dogs with dilated cardiomyopathy, transvenous access to the right ventricle could not be achieved, but left ventricular biopsy was performed without complication. Complications were infrequent, and dogs recovered to at least their baseline status within 48 hours. Evaluation of the efficacy and complication rate of the procedure with each of the 2 biopsy instruments currently available identified no differences between them. PMID- 2240805 TI - Evaluation of drug-induced prostatic involution in dogs by transabdominal B-mode ultrasonography. AB - The relative antiandrogen-induced prostate involution activity of the newly synthesized hydroxyflutamide pro-drug was compared with that of flutamide in 25 Beagles. Secondary antiandrogen activity of both drugs on the testes and mammary tissue was investigated. Daily oral administration of both compounds at 2 dosages (ie, 2.5 and 5.0 mg/kg of body weight) during a 7-week period was monitored by transabdominal ultrasonography of the prostate twice a week. Cross-sectional area estimates of the prostate gland calculated from oblique dorsoventral, and transverse sonographic measurements were diminished significantly in some of the treated dogs as early as day 14 of drug administration. All treated dogs had significant differences in reduction by day 47. Involution was related directly to dose (P less than 0.05), but no difference was observed between test compounds. Differences in secondary antiandrogen activity were not remarkable. Flutamide was not found to have any activity advantage in vivo over hydroxyflutamide. It was concluded that ultrasonography can be a highly effective means of monitoring prostate size, and of monitoring drug-induced involution over time. PMID- 2240806 TI - Correlation of brain stem auditory-evoked responses with cranium size and body weight of dogs. AB - Brain stem auditory-evoked responses were recorded in 9 male and 11 female clinically normal mature dogs, weighing between 2 and 36 kg. Mean wave latency for the entire group of dogs, using 60-dB hearing level click stimuli at 11/s for waves I to VII was: 1.41, 2.21, 2.85, 3.31, 3.71, 5.12, and 6.46 ms, respectively. The mean interpeak latency for waves I and V (IPLIV) was 2.32 ms. Neither gender nor ear effect was detectable. Positive correlation was observed between cranium length, cranium width, nasion-external auditory meatus interval, and body weight for wave-V latency and IPLIV. Such correlation was not documented for wave I. The regression equations for their effects on IPLIV were: cranium length, y = 0.05x + 1.85; cranium width, y = 0.07x + 1.32; nasion-external auditory meatus interval, y = 0.05x + 1.79; and body weight, y = 0.01x + 2.15. On the basis of any of the 3 variables of cranium size or body weight, the study population could be classified into groups of large and small dogs, with the large group having significantly (P less than 0.05) longer latency for wave V and IPLIV. It is recommended that the effect of size variation in dogs on brain stem auditory-evoked responses should be compensated for by use of the regression equation based on cranium length. PMID- 2240807 TI - Morphologic and ultrastructural evaluation of effect of ischemia and dimethyl sulfoxide on equine jejunum. AB - Morphologic changes in equine jejunal segments subjected to 1 hour of ischemia and 1 hour of reperfusion, and protective effects of systemic administration of dimethyl sulfoxide (DMSO; 1 g/kg of body weight) were investigated in 18 ponies, using light microscopy and scanning and transmission electron microscopy. Ponies were allotted to 4 groups: group 1--control (n = 3); group 2--DMSO (n = 3); group 3--ischemia (n = 6); and group 4--ischemia and DMSO (n = 6). In each pony, 2 jejunal sections were evaluated. The first section was obtained prior to induction of ischemia, and the second was obtained 2 hours later after reperfusion. Mucosal lesions were graded from 0 (normal) to 5 (most severe). Combined ischemia and reperfusion of 2 hours' duration induced moderately severe mucosal injury to the equine jejunum (group 3; grade 1.5 to 2.5), characterized principally by disruption of enterocyte attachment from the basement membrane and lamina propria. Fluid accumulation disrupted enterocyte cell-to-cell adhesion toward cell bases, while apical tight junctions and desmosomal junctions toward the luminal surface remained intact. Intracytoplasmic organellar changes within enterocytes were not a prominent feature of the injury. The aforementioned processes were marked at the villus tip and progressed down the villus sides. These findings support the importance of mechanisms leading to early subepithelial fluid accumulation rather than that of direct severe enterocyte injury. Further, fluid accumulation does not appear to arise from intercellular migration from the luminal surface. In this model, a pathomechanical effect caused by vigorous villus retraction appears to exacerbate epithelial lifting toward the villus tip.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240808 TI - Clinical and pathologic studies of experimentally induced Pasteurella haemolytica pneumonia in calves. AB - Pasteurella haemolytica pneumonia of the right caudal lung lobe was experimentally induced in 2-week-old Holstein calves (n = 11) by endobronchial inoculation of 7.9 x 10(10) colony-forming units of 6-hour log-phase bacteria. Calves were studied for 72 hours after inoculation. The challenge procedure consistently induced a lesion in the right caudal lung lobe, which was consistent radiographically with results of pathologic examination and a similar volume of bronchography contrast medium. Clinically, the calves developed a significant increase in rectal temperature within 24 hours after inoculation. Seventy-two hours after inoculation, the total WBC counts, absolute band neutrophil counts, monocyte counts, and blood fibrinogen concentrations were significantly higher than normal and albumin concentration was significantly decreased. Necropsy revealed a circular to oblong lesion that was congested, edematous, and firm and occupied 20 to 40% of the right caudal lung lobe. Histologic examination revealed a severe acute inflammatory reaction characterized by cellular exudate and proteinaceous fluid in the alveoli, interlobular septa, and pleura. PMID- 2240809 TI - Pneumonic pasteurellosis induced experimentally in gnotobiotic and conventional calves inoculated with Pasteurella haemolytica. AB - Experimental pneumonia caused by Pasteurella haemolytica was induced in 2-week old gnotobiotic (n = 4) and conventional (n = 6) calves by endobronchial inoculation into the right caudal lung lobe of 7.9 x 10(10) +/- 0.6 x 10(10) (mean +/- SD) colony-forming units of P haemolytica in the 6-hour log phase of growth. The calves were studied for 24 hours or less. Regression lines for the relationship between clinical index and time for the gnotobiotic group and conventional group of calves were compared, and the clinical index was found to be significantly (P less than or equal to 0.005) more rapid in the gnotobiotic group. There was also a significant difference in the preinoculation, absolute segmented neutrophil count (P less than or equal to 0.05), and in the total serum protein, albumin, and globulin values (P less than or equal to 0.05). Comparison of the preinoculation and post inoculation blood cell and blood chemical values revealed a significant increase (P less than or equal to 0.05) in the numbers of band neutrophils and fibrinogen in conventional calves, and a significant decrease (P less than or equal to 0.05) in the total WBC count in gnotobiotic calves. Necropsy of both groups of calves revealed a circular to oblong lesion that was congested, edematous, and firm, and which occupied 20% to 100% of the right caudal lung lobe and involved the remaining lung lobes to a more minor degree. When mean lesion scores of the 2 groups of calves were compared, no significant difference (P less than or equal to 0.05) was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240810 TI - Effect of in-house transport on murine plasma corticosterone concentration and blood lymphocyte populations. AB - The effect of in-house transport on plasma corticosterone concentration and blood lymphocyte populations of laboratory mice was investigated. Mice were transported within a research facility at 0900 hours in a pattern designed to simulate that commonly used by investigators prior to experimental manipulation. Plasma corticosterone concentration and WBC count were determined at 0.25, 2, 4, 8, 12, and 24 hours after transport. A significant (P less than 0.05) increase in plasma corticosterone concentration was seen in mice immediately after transport. The normal circadian rhythm of plasma corticosterone concentration was altered for the subsequent 24-hour period. Corresponding significant (P less than 0.05) decreases in total WBC numbers, lymphocyte count, and thymus gland weight were observed. The decrease in total blood lymphocyte numbers at 4 hours was reflected in B- and T-lymphocyte populations. The subsequent acute increase in plasma corticosterone concentration was associated with alterations in the cellular components of the immune system. Results of the study indicated that routine in house transport of laboratory mice should be considered a stressful stimulus. PMID- 2240811 TI - Cultivation of tissue from the matrix of the stratum medium of the equine and bovine hoof walls. AB - Explants from the matrix of the stratum medium of the wall of the equine and bovine hoof each were cultured on a microporous membrane, using a standard culture medium. After incubation at 37 C, the outgrowth was a mixture of keratinocytes and fibroblasts, with predominance of the latter. After incubation at 34 C, the keratinocytes dominated, covering the lateral surfaces of the explant as well as the basal surface. Lateral outgrowth of keratinocytes was observed at the borderline of the original epidermis and at the borderline of the explant's contact with the membrane. Epithelial outgrowth from the former consisted of rounded aggregates protruding into the medium, whereas outgrowth from the latter formed a pluristratified carpet occupying a considerable part of the membrane. In the outer layers, keratinocytes covering the cut surfaces of the dermis of the explant had a differentiation pattern of the kind that characterizes the keratinocytes of the hoof; differentiation was not observed in the lateral outgrowth. PMID- 2240812 TI - Detection of capsular polysaccharide in milk of cows with natural intramammary infection caused by Staphylococcus aureus. AB - Detection of capsular polysaccharide (CP) in milk of cows with natural intramammary infection caused by Staphylococcus aureus was attempted. Five quarters of 5 cows harboring S aureus strains that produce type-8 CP were selected. Using an ELISA with a monoclonal antibody, type-8 CP was not detected in extracts prepared from fresh milk collected aseptically. By contrast, CP was easily detectable after incubation of infected milk at 38 C for 20 hours. Quantitation of CP in extracts from incubated milk samples by use of ELISA indicated a great variation of CP expression by strains. Although an incubation step was necessary to detect CP, results of the study indicate that CP may be expressed in vivo during intramammary infection caused by S aureus. PMID- 2240813 TI - In vitro susceptibility of some porcine respiratory tract pathogens to aditoprim, trimethoprim, sulfadimethoxine, sulfamethoxazole, and combinations of these agents. AB - The in vitro antimicrobial activities of aditoprim (AP), a new dihydrofolate reductase (DHFR) inhibitor, trimethoprim (TMP), sulfadimethoxine (SDM), sulfamethoxazole (SMX), and combinations of these drugs against some porcine respiratory tract pathogens were determined by use of an agar dilution method. The minimal inhibitory concentrations (MIC) of these agents were determined twice against Bordetella bronchiseptica (n = 10), Pasteurella multocida (n = 10), and Actinobacillus pleuropneumoniae (n = 20) strains isolated from pigs suffering from atrophic rhinitis or pleuropneumonia. All B bronchiseptica strains were resistant to AP and TMP. The MIC50 values of AP and TMP for P multocida were 0.25 and 0.06 microgram/ml, respectively, and for A pleuropneumoniae, 1 and 0.25 microgram/ml, respectively. The MIC50 values of SDM and SMX for B bronchiseptica were 4 and 1 micrograms/ml, respectively; for P multocida, 16 and 8 micrograms/ml, respectively; and for A pleuropneumoniae, 16 and 8 micrograms/ml, respectively. The investigated combinations of the DHFR inhibitors and the selected sulfonamides had synergism for the A pleuropneumoniae strains; the MIC90 values of the combinations were less than or equal to 0.06 microgram/ml. Potentiation was not observed for the B bronchiseptica and the P multocida isolates. The MIC of the combinations against B bronchiseptica and P multocida corresponded respectively to the concentrations of the sulfonamides and the DHFR inhibitors in the combinations. For A pleuropneumoniae, 2 types of strains were used (25% of serotype 2 and 75% of serotype 9). Type-2 strains had lower susceptibility than type-9 strains to AP and TMP as well as to SDM and SMX (at least a fourfold difference in MIC between the 2 types of strains).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240814 TI - Hematologic values and plasma and tissue folate concentrations in dogs given phenytoin on a long-term basis. AB - During earlier investigations of the hepatic effects in dogs of long-term administration of phenytoin alone or in combination with primidone, erythrocytic macrocytosis, neutropenia, neutrophilic hypersegmentation, and thrombocytopenia were observed. Such abnormalities were observed most often in dogs given phenytoin and resembled those known to be attributable to folate deficiency in human beings with epilepsy treated with phenytoin. To pursue the theory that these hematologic aberrations were caused by drug-induced folate deficiency, 12 dogs were given a diet specifically formulated to contain a minimally adequate concentration of folate. After 2 weeks, phenytoin was administered daily (400 mg, PO, q 8 h) to 8 of the 12 dogs for 54 weeks. A CBC, bone marrow aspiration biopsy, and measurement of plasma and RBC folate concentrations were done every 3 weeks. Bone marrow aspirates were examined by transmission electron microscopy after 24 and 36 weeks, and at the end of the treatment period. Hepatic folate concentration was also determined in all dogs before and after treatment. Excretion of formiminoglutamic acid, as a marker of folate deficiency, was measured in all dogs at the end of the study. All dogs remained healthy throughout the treatment phase. Consistent abnormalities were not observed in the blood or bone marrow of treated dogs. Plasma and RBC folate concentrations decreased in control and treated dogs as a result of dietary restriction (P less than or equal to 0.02), and remained stable until the end of the study. The RBC folate content decreased further in treated dogs (P less than or equal to 0.02), although the hepatic folate content was similar in control and treated dogs. Treated dogs did not excrete formiminoglutamic acid more rapidly than did control dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240815 TI - Effect of T-2 toxin on resistance to systemic Salmonella typhimurium infection of newly hatched chickens. AB - Newly hatched chickens were treated with the trichothecene mycotoxin, T-2 toxin, during the first day of life. Control chickens were treated with other agents known to cause immunosuppression--cyclosporine, cyclophosphamide, and aflatoxin. Chickens were infected on day 6 (5 days after treatment with T-2 toxin) by intraperitoneal inoculation with Salmonella typhimurium. Blood samples were collected from treated chickens (noninfected) and used to assess the responsiveness of blood lymphocytes to T-cell or B-cell mitogens, phytohemagglutinin, or lipopolysaccharide, respectively. The T-2 toxin had a profound negative effect on the ability of the chickens to resist salmonellosis, as measured by survival. However, the toxin effect in reducing phytohemagglutinin and lipopolysaccharide-stimulated mitogenesis, though significant (P greater than 0.05), was not severe. Our data indicate a direct effect of T-2 toxin on native resistance to systemic salmonellosis, which was not accompanied by marked alteration in T- or B-cell responses to mitogenic stimulation. PMID- 2240817 TI - Horseradish peroxidase study of the location of extrinsic efferent and afferent neurons innervating the colon of dogs. AB - The abdominal portion of the colon of 13 clinically normal dogs was divided into 5 regions (ascending, transverse, left colic flexure, proximal descending, and distal descending), and each region was injected with 30 mg of horseradish peroxidase (HRP). The injected colonic region, brain stem, L7-Cd1 portion of the spinal cord, sympathetic trunk ganglia, celiacomesenteric ganglia, caudal mesenteric ganglion, pelvic plexi, distal vagal (nodose) ganglia, and L1-Cd1 spinal ganglia were obtained at post-injection hour 48, sectioned, and processed by use of the tetramethylbenzidine method. The entire length of the colon was found to be under extrinsic influence of the parasympathetic nucleus of cranial nerve X (PX), with the largest average number of labeled cells resulting from injection of the ascending colon. It was also indicated that the entire colon is under extrinsic influence of the sacral portion of the spinal cord because the pelvic ganglia (second-order neurons) of the pelvic plexi contained labeled cells for all colonic regions. The largest average number of labeled cells in pelvic ganglia was seen after injection of the distal portion of the descending colon. Only after injection of the distal portion of the descending colon were labeled cells found in the S1-S3 portion of the spinal cord. Labeled cells in the PX, spinal cord, and pelvic ganglia were found bilaterally. Although the entire abdominal portion of the colon appears to be influenced by cranial and sacral parasympathetic preganglionic (via pelvic ganglia) neurons, the relative importance of the 2 areas seems to be reversed between the ascending colon and distal portion of the descending colon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240816 TI - Anthelmintic activity of the macrocyclic lactone F28249-alpha in sheep. AB - The macrolytic lactone F28249-alpha was titrated in experimentally infected sheep and found to be highly effective against most of the common gastrointestinal nematodes as a single oral dose, given at a rate of 0.025, 0.05, or 0.1 mg/kg. Specifically, maximal activity was evident at even the lowest dosage against adult Haemonchus contortus, Ostertagia circumcinta, Trichostrongylus axei, and T colubriformis and L4 O circumcinta. Activity against Oesophagostomum columbianum was also high at all dosages, with a calculated ED95 of 0.029 mg/kg. Cooperia curticei was eliminated at 0.1 mg/kg, but control was erratic at the lower dosages. The greatest weakness of this compound was its activity against C oncophora. The activity against this parasite was weak (less than or equal to 85%) at all dosages, and the dosage-response curve was flat, suggesting dosages substantially higher than those given would be necessary for high-order control of this species. PMID- 2240818 TI - Plasma glucocorticoid concentrations in calves as an indicator of stress during parturition. AB - Plasma glucocorticoid concentrations and blood gas values were determined for 6 days in 47 newborn calves that had been subjected to various obstetrical procedures at term. Concentrations of glucocorticoids were uniformly high at birth (70 to 103 ng/ml). Increasing degrees of acidosis were accompanied by increasing glucocorticoid concentrations in plasma. Plasma glucocorticoid concentrations decreased sharply during the first 6 hours after delivery and reached a plateau at 48 hours after birth (14 to 21 ng/ml). The latter was taken as an indication that adaptation had been achieved. Calves subjected to severe pulling had higher glucocorticoid concentrations at birth (110.4 ng/ml) than calves requiring no assistance (88.3 ng/ml), calves requiring only slight assistance (83.8 ng/ml), or calves that had been delivered by cesarean section (82.9 ng/ml). PMID- 2240819 TI - Characterization of distal bronchial microflora during acute exacerbation of chronic bronchitis. Use of the protected specimen brush technique in 54 mechanically ventilated patients. AB - To obtain accurate information on distal bronchial microflora during acute exacerbation in patients with chronic bronchitis, we prospectively studied 54 such patients who had been receiving mechanical ventilation because of hypercapnic respiratory failure. Fiberoptic bronchoscopy using a protected specimen brush (PSB) was performed on each patient within the first 24 h after admission. Cultures of protected brush specimens demonstrated no growth in 27 patients (50%). With the exception of fever (38.2 +/- 0.8 versus 37.7 +/- 0.6 degrees C; p less than 0.05), the initial severity of the episode of exacerbation was similar in patients with and without infection. A total of 44 organisms were isolated in the 27 patients with positive cultures; the predominant pathogens were Hemophilus spp. and Streptococcus spp. (involved in 74% of cases), but other organisms were isolated in 12 of 27 patients. Mortality rates, duration of mechanical ventilation, and duration of hospitalization were not significantly different between patients with bronchial microflora treated with appropriate antimicrobial therapy (n = 27) and patients without bronchial microflora either receiving empirical antibiotic therapy (n = 18) or not (n = 9). These data suggest that distal bronchial infection due to the usual pathogens, as far as shown by protected specimen brush cultures, may not be the sole or even the predominant cause of acute exacerbation of chronic bronchitis in patients requiring mechanical ventilation. PMID- 2240820 TI - Distinguishable types of dyspnea in patients with shortness of breath. AB - Dyspnea frequently accompanies a variety of cardiopulmonary abnormalities. Although dyspnea is often considered a single sensation, alternatively it may encompass multiple sensations that are not well explained by a single physiologic mechanism. To investigate whether breathlessness experienced by patients represents more than one sensation, we studied 53 patients with one of the following seven conditions: pulmonary vascular disease, neuromuscular and chest wall disease, congestive heart failure, pregnancy, interstitial lung disease, asthma, and chronic obstructive pulmonary disease. Patients were asked to choose descriptions of their sensation(s) of breathlessness from a dyspnea questionnaire listing 19 descriptors. Cluster analysis was used to identify natural groupings among the chosen descriptors. We found that patients could distinguish different sensations of breathlessness. In addition, we found an association between certain groups of descriptors and specific conditions producing dyspnea. These findings concur with those in an earlier study in normal volunteers in whom dyspnea was induced by various stimuli. We conclude that different types of dyspnea exist in patients with a variety of cardiopulmonary abnormalities. Furthermore, different mechanisms may mediate these various sensations. PMID- 2240821 TI - A family study of the variability of pulmonary function in alpha 1-antitrypsin deficiency. Quantitative phenotypes. AB - A group of 52 alpha 1-antitrypsin-deficient individuals of phenotype Pi Z and 117 of their relatives underwent a protocol including pulmonary function testing, completion of a questionnaire, and blood donation. Our population permitted a minimum frequency estimate (7 x 10(-4)) for Pi null alleles. Five quantitative phenotypes were measured, including FEV1, FEF25-75, total serum alpha 1AT, oxidized serum alpha 1AT, and total serum IgE. We found that (1) total alpha 1AT levels were higher in Pi Z subjects with lung function impairment (FEV1 less than or equal to 65% of predicted) than in Pi Z subjects who were not impaired; (2) Pi Z subjects with lung function impairment had elevated serum levels of oxidized alpha 1AT; and (3) IgE levels were relatively elevated in first-degree Pi MZ relatives of impaired Pi Z subjects. Moreover, FEV1 tended to be relatively reduced in heterozygous parents of impaired Pi Z subjects, suggesting that a subset of Pi MZ individuals are at risk for development of lung disease because of familial factors. These results represent an initial step toward the development of intermediate phenotypes that will be predictive of a severe course in alpha 1AT deficiency; they suggest that, in addition to cigarette smoking, atopic predisposition and undetermined familial factors may be important codeterminants of lung disease progression. PMID- 2240822 TI - The single-breath nitrogen test, mortality, and cancer. AB - The relationship between indices of the single-breath nitrogen test and mortality, overall cancer incidence, and respiratory cancer incidence was examined in a cohort of 876 men, 46 to 69 yr of age, examined in 1974 and followed until June 1985. Closing volume, closing capacity, and slope of phase III were not related to mortality or cancer. In contrast, FEV1 was related to mortality, with an estimated relative mortality risk of 1.37 (95% confidence interval, 1.11 to 1.70) per liter under the expected FEV1, given height, age, and smoking, but FEV1 was not related to cancer. Inability to perform acceptable single-breath nitrogen test tracings was related to mortality with a relative mortality risk of 2.03 (1.45 to 2.85), but not to cancer. We conclude that indices of the single-breath nitrogen test have no predictive value concerning overall mortality and cancer incidence. PMID- 2240823 TI - Pulmonary function after heart-lung transplantation using larger donor organs. AB - Restrictive pulmonary function after heart-lung transplantation (HLT) has been attributed to the use of smaller donor lungs and/or an inability to generate normal negative pleural pressures. Pleural pressure generation depends on both the size of the recipient thoracic cage and its neuromuscular integrity. To determine whether lung volumes after heart-lung transplantation are more dependent on donor lung size or on recipient chest wall characteristics, seven HLT recipients were evaluated before and after transplantation. Postoperative values initially (average, 2 months), 6, and 12 months after transplantation were compared with predicted lung volumes for the recipient and donor organs. TLC dropped from a mean of 5.2 +/- 0.5 L preoperatively to 3.7 +/- 0.3 L (p less than 0.05) 2 months after HLT, but it improved with time and ultimately was not different from preoperative values. The predicted TLC of the HLT donor organs were significantly larger than those of the recipient's predicted TLC, with a mean of 6.9 +/- 0.4 versus 5.3 +/- 0.3 L (p less than 0.05). DLCO, arterial PO2, and PCO2 did not change after surgery. Within limits, larger donor lungs appear to adapt to the constraints of the recipient chest and may be used with clinical success, without apparent adverse effects. PMID- 2240824 TI - Cholinergic control of human airways in vitro following extrinsic denervation of the human respiratory tract by heart-lung transplantation. AB - In heart-lung transplantation (HLT), the airways have been assumed to be denervated since cholinergic, adrenergic, and sensory nerves are severed. Challenge studies of such patients suggest that there is an increase in airway responsiveness to inhaled cholinergic agonists, which may be explained by denervation hypersensitivity of muscarinic receptors on airway smooth muscle. We have studied the cholinergic control of airways from lungs removed from five patients (8 to 31 yr of age) undergoing retransplantation because of rejection related bronchiolitis, with time since transplantation ranging from 12 to 32 months. These airways were compared with airways obtained from eight heart donors (24 to 42 yr of age) and from five patients undergoing surgical lobectomy for bronchial carcinoma (54 to 72 yr of age). Bronchial rings (distal lobar and subsegmental) were mounted in organ baths and isometric contractile responses measured. Contractile responses to acetylcholine (ACh, 10 nM to 10 mM) and to electrical field stimulation (EFS) (40 V, 0.5 ms, 1 to 64 Hz for 15 s) were determined. Transplant and control airways showed the same response to ACh, with mean EC50 values of 61.0 +/- 0.32 microM for HLT patients, 57.6 +/- 0.24 microM for donor patients, and 48.7 +/- 1.2 microM for lobectomy patients, suggesting no denervation hypersensitivity of muscarinic receptors. EFS, which activates postganglionic cholinergic nerves, caused similar frequency responses in both transplant and control airways, suggesting that postganglionic nerves are intact. [3H]quinuclidinyl benzilate binding to membranes prepared from lung was performed to determine muscarinic binding characteristics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240825 TI - Pulmonary denervation in humans. Effects on dyspnea and ventilatory pattern during exercise. AB - The role of the pulmonary autonomic nerves in the mediation of respiratory sensation is unclear. Pulmonary neurogenic mechanisms may contribute to dyspnea either directly or indirectly via an influence on the pattern of ventilation. Using human heart-lung transplantation as a model of pulmonary denervation, we studied the ventilatory response, respiratory drive (P0.1), and sensation of breathlessness (modified Borg scale) during maximal incremental bicycle exercise. The subjects were four female heart-lung transplant recipients 3 to 9 months post transplant and 10 age-matched control subjects. The ventilatory response to increasing CO2 output (VCO2) was higher (p less than 0.001) in transplant recipients than in control subjects, such that ventilation at peak exercise was similar in the two groups despite a lower peak VCO2 in transplant recipients. The ratio of tidal volume to inspiratory capacity increased with increasing ventilation in a similar fashion in both groups. Although the respiratory rate increased more quickly in transplant recipients, it was similar at peak ventilation in the two groups. Ventilatory timing and duty cycle at half-peak and peak ventilation were similar in transplant recipients and control subjects. Dyspnea ratings were not different between the two groups at similar levels of ventilation. Dyspnea as a function of P0.1 was also similar in transplant and control groups. These results indicate that pulmonary neurogenic mechanisms play a role in determining the level, but not the pattern, of ventilation during exercise. Furthermore, these pathways do not appear to contribute significantly to the perception of breathlessness in normal humans. PMID- 2240826 TI - Mechanical action of the interosseous intercostal muscles as a function of lung volume. AB - On the basis of local stimulation of individual muscles, it has been suggested that both the external (EI) and internal interosseous intercostal muscles have an inspiratory action at low lung volumes and an expiratory action at high lung volumes. In this study, we assessed the action of the interosseous intercostal muscles at different lung volumes in 19 anesthetized dogs by synchronously activating the intercostal muscles via ventral root stimulation (VRS). An electrode was positioned on the upper thoracic spinal cord according to previously described techniques. The cervical phrenic rootlets were sectioned bilaterally, the accessory muscles were sectioned from the rib cage, and the origins of the abdominal muscles were sectioned from the middle region of the rib cage. Changes in airway pressure (delta P) were monitored during the application of supramaximal stimuli after hyperventilation-induced apnea and during airway occlusion. Animals were passively inflated or deflated with a volume syringe. Precontractile airway pressure was used as an index of lung volume. External and parasternal intercostal muscle (PA) lengths were monitored by sonomicrometry in the third intercostal space. Thoracoabdominal motion was monitored by Respitrace bands. During VRS, both PA and EI shortened at all lung volumes. Mean delta P progressively decreased with increasing lung volume. At precontractile airway pressures of -10, 0, and +30 cm H2O, delta P were -25 +/- 1, -16 +/- 1, and -5 +/ 1 cm H2O, respectively. After section of the internal intercostal nerves lateral to the costochondral junctions from the first through the seventh intercostal spaces to eliminate PA action, EI shortened, whereas PA usually lengthened.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240827 TI - Effect of corticosteroids on respiratory muscle histopathology. AB - Pathologic alterations induced by corticosteroid administration were evaluated in the respiratory muscles and compared to those in the peripheral skeletal muscles of the rabbit. Alterations in gross and microscopic pathology as well as histochemistry were determined in the diaphragm, intercostal, sternocleidomastoid, extensor digitorum longus, and soleus muscles following 3 wk of intramuscular cortisone injections. Corticosteroid administration induced significant pathologic changes in all the muscles except the soleus. Although gross pathologic changes were greatest in the extensor digitorum longus, microscopic changes were greatest in the diaphragm. Reductions in total muscle fiber volume were similar in the diaphragm, sternocleidomastoid, and extensor digitorum longus muscles. The composition of muscle fiber types and the number of fibers in a muscle were not altered in any of the muscles studied following corticosteroids. There was significant atrophy of individual muscle fibers in all the muscles except the soleus. In the diaphragm, corticosteroids induced atrophy of all fiber types, including type I fibers. Atrophy of type I fibers was not present in the peripheral skeletal muscles or the other respiratory muscles. On the other hand, corticosteroids induced selective atrophy of type IIb muscle fibers in the intercostal and sternocleidomastoid muscles similar to that in the peripheral skeletal muscles. These findings suggest that the effect of corticosteroids on the diaphragm is unique, and one cannot extrapolate form the effect of corticosteroids on peripheral skeletal muscles to that in the diaphragm. In addition, these pathologic changes may have functional relevance, since atrophy of type I fibers may result in a reduction in muscle endurance. PMID- 2240828 TI - The role of mucous glycoproteins in the rheologic properties of cystic fibrosis sputum. AB - Cystic fibrosis (CF) is characterized by excessive amounts of thick and tenacious mucous secretions that obstruct organ ducts and passages. In the respiratory tract this is associated with chronic infection resulting in the hypersecretion of purulent sputum, which the patient finds difficult to clear. We have studied the rheologic properties of purulent sputum from six patients with CF and five patients with chronic bronchitis to assess whether CF is associated with increased sputum viscoelasticity. In addition, we have isolated the major rheologic determinants, mucous glycoproteins, from CF and chronic bronchitis sputa and, using a magnetic microrheometer, investigated the possibility that the altered properties of mucus in CF are associated with abnormalities in these glycoproteins. Creep compliance analysis indicated that the CF sputa possessed raised levels of both elasticity (p less than 0.01) and viscosity (p less than 0.01). These increases in both rheologic parameters were found to be associated with increases in the DNA content (p less than 0.01) and dry weight (p less than 0.05). Mucous glycoproteins were isolated from CF and chronic bronchitis sputum samples by gel filtration on Sepharose CL4B, followed by concentration to form 8% wt/wt gels. In the absence of other sputum components, no abnormality in the rheologic properties of CF mucin gels could be detected. However, when DNA was added, the CF gels responded with increases in both elasticity and viscosity of as much as 30% (p less than 0.05), an effect not observed in the chronic bronchitis gels. These results suggest that a subtle abnormality may exist in CF mucous glycoproteins and that this could have a role in the altered physical properties of mucous secretions in CF. PMID- 2240830 TI - Determination of serum concentrations of type III procollagen peptide in mechanically ventilated patients. Pronounced augmented concentrations in the adult respiratory distress syndrome. AB - Type III procollagen peptide (PCP) is a byproduct of type III collagen synthesis and a potential marker of collagen secretion. In chronic diffuse interstitial lung diseases, elevated PCP concentrations have been found in serum as well as in bronchoalveolar lavage fluid. It has been proposed that PCP is a marker of early, active stages of fibrosis. As severe fibrosis is a frequent complication in adult respiratory distress syndrome (ARDS), we investigated PCP in patients with ARDS and compared the results with those from patients requiring mechanical ventilation because of heart failure and after neurosurgical and surgical interventions, and those from spontaneously breathing patients, including healthy volunteers and patients with pneumonia, liver cirrhosis, and renal failure. PCP concentrations in patients with ARDS were extremely elevated compared with those in control subjects (p less than 0.001) and correlated positively with FiO2 (r = 0.71, p less than 0.01). These results support the pathophysiologic concept of early fibrogenesis in ARDS. As preventing pulmonary fibrosis in ARDS is essential in improving survival rate, we believe PCP can be a valuable diagnostic tool in ARDS. PMID- 2240829 TI - Failure of high-dose vitamin E to correct ceruloplasmin ferroxidase deficiency in cigarette smokers. AB - Cigarette smokers have a biochemical defect in the ferroxidase activity of their serum ceruloplasmin. Ceruloplasmin is one of the main serum antioxidants, and this defect in ferroxidase activity most likely accounts for the previously observed decrease in smoker serum antioxidant activity. This defect may be related to oxidation of ceruloplasmin in the lung. We hypothesized that vitamin E might be able to reverse the decrease in smoker ferroxidase activity and thus restore serum antioxidant activity. To test this hypothesis, we administered high dose vitamin E to a group of young asymptomatic cigarette smokers (n = 8). Although serum levels of vitamin E significantly increased (8.7 +/- 0.8 to 20.6 +/- 3.1 micrograms/ml, p = 0.01), the ferroxidase activity of smoker serum (0.139 +/- 0.02 (0.139 +/- 0.02 to 0.144 +/- 0.03 U/ml, p = 0.824), and the antioxidant activity of serum (45.8 +/- 7.2 to 51.6 +/- 8.4%, p = 0.587) remained unchanged. Thus, at the current dose and duration of supplementation, vitamin E was unable to reverse the defect in smoker serum ferroxidase activity and thus unable to augment the antioxidant capacity of the serum. PMID- 2240831 TI - Effect of pentoxifylline on hemodynamics, alveolar fluid reabsorption, and pulmonary edema in a model of acute lung injury. AB - We investigated the effect of pentoxifylline (PTX) on the development of pulmonary edema in a model of adult respiratory distress syndrome in rabbits. Lung injury was induced by repeated saline lavages in adult rabbits weighing 2.5 to 3.5 kg. Rabbits pretreated with PTX (20 mg/kg bolus followed by 20 mg/kg/h infusion) developed significantly lower amounts of lung edema 4 h after saline lavage (extravascular lung water to dry weight ratio [W/D], 6.9 +/- 0.6 SD versus 8.9 +/- 0.5 in control animals). PTX produced a 25% increase in cardiac output, but there were no differences between treated and untreated groups in calculated pulmonary vascular resistance or microvascular pressure. To determine whether PTX could have lowered pulmonary venous resistance and thus lowered effective microvascular pressure for fluid filtration, we directly measured pulmonary artery and left atrial pressures, and measured by micropuncture the pressure in 20 to 40 microns subpleural venules in four open-chested rabbits 3 to 4 h after lavage. Venous resistance was low (venous pressure drop 0.9 +/- 0.1 mm Hg) and was unchanged by PTX infusion. To determine if PTX decreased lung water by accelerating active alveolar fluid reabsorption, a single 60-ml aliquot of saline was instilled into the lungs of normal rabbits treated with saline or PTX. Both groups had a similar decrease in lung water content 1 and 4 h later. Our data indicate that PTX reduces edema formation in rabbits after saline lavage, not by lowering microvascular pressures for fluid filtration or by acceleration alveolar fluid reabsorption, but possibly by its anti-inflammatory effect on neutrophil function. PMID- 2240832 TI - IgG1-mediated acute pulmonary hypersensitivity response in the guinea pig. Involvement of specific lipid mediators. AB - We determined the pulmonary obstructive response to aerosolized antigen challenge, and its sensitivity to antagonists of specific lipid mediators, in IgG, passively sensitized (IgG1-PS) guinea pigs. Antiovalbumin (OA)-IgG1 was isolated by affinity chromatography from serum derived from actively immunized Hartley guinea pigs. Propranolol and pyrilamine pretreated, IgG1-PS guinea pigs were challenged with aerosolized antigen and pulmonary obstruction was quantified by measurements of excised lung gas volume (ELGV). ELGV increased between 150 and 1,035% in a dose-proportional fashion with increasing antigen exposure (0.001 to 0.1% nebulizer concentration). The leukotriene antagonists ICI-204,219 and SKF 104,353 exhibited dose-proportional inhibitions in antigen-induced elevations in ELGV, inhibiting up to 65 and 87% at the maximal concentrations examined. Similarly, the platelet-activating factor (PAF) antagonists WEB-2086 and L 659,989 inhibited antigen-induced elevations in ELGV, inhibiting up to 94 and 59% at the maximal concentrations examined. In contrast, the cyclooxygenase (CO) inhibitor piroxicam significantly enhanced (p less than 0.05) the OA-induced elevations in ELGV. Aerosolized PAF challenge produced dose-proportional elevations in ELGV that were significantly inhibited by the LTD, antagonist ICI 204,219 (38 and 43% inhibition) and the CO inhibitor piroxicam (62 and 48% inhibition) in sensitized and nonsensitized animals, respectively. We hypothesize that IgG1-dependent airway obstruction is mediated in part by LTD, produced in response to PAF generation. PMID- 2240833 TI - The penetration of aminoglycosides into the alveolar lining fluid of rats. The effect of airway inflammation. AB - The concentration-time profile of gentamicin and tobramycin in the alveolar lining fluid (ALF) of rats was determined after intravenous bolus injection using bronchoalveolar lavage (BAL). BAL can be used for evaluating the penetration of both aminoglycosides into the ALF if highly sensitive detection methods are used, and an endogenous marker (urea) can be applied to avoid the unpredictable dilutional effect of the lavage procedure. The concentration of gentamicin and tobramycin in ALF reached a peak after 5 and 10 min, respectively, and remained high when plasma concentrations were declining, suggesting an accumulation reservoir in the lung acini. The ratio of the AUC of the concentration-time profile in ALF and plasma was 0.67 and 0.45 for gentamicin and tobramycin, respectively. The penetration of both aminoglycosides into the ALF was significantly higher after induction of airway inflammation by inhalation of endotoxin. The ratio of the AUC in ALF and plasma in the endotoxin-exposed animals was 0.76 and 0.55 for gentamicin and tobramycin, respectively. The ratio of the AUC of the concentration-time profile of gentamicin in ALF to that of tobramycin was 1.27 without inflammation and 1.44 after endotoxin exposure. Thus, both with and without inflammation, gentamicin penetrates better into the ALF than does tobramycin. PMID- 2240834 TI - Enzymatic modulation of vasoactive intestinal peptide and nonadrenergic noncholinergic inhibitory responses in guinea pig tracheae. AB - The airways of the guinea pig are innervated by four types of autonomic nerves: cholinergic excitatory, adrenergic inhibitory, nonadrenergic noncholinergic (NANC) excitatory, and NANC inhibitory. Tachykinins (neurokinins A and B and substance P) are believed to mediate NANC excitatory responses, and vasoactive intestinal peptide (VIP) has been proposed as the chemical mediator of the NANC inhibitory system. Enzymatic degradation represents an important means by which the biologic actions of neurotransmitters are terminated. In the present study, relaxation responses of guinea pig tracheae to NANC nerve stimulation and to exogenous VIP administration were compared in the absence and presence of various peptidase inhibitors. NANC inhibitory responses elicited by electrical field stimulation were unaffected by aprotinin or soybean trypsin inhibitor but were depressed by thiorphan or leupeptin. Concentration-response curves to exogenous VIP were shifted to the left by soybean trypsin inhibitor but were not affected by aprotinin, leupeptin, or thiorphan. After tachykinin depletion with capsaicin, thiorphan also induced a leftward shift in the VIP concentration-response curve. Under the same conditions, thiorphan failed to influence NANC inhibitory responses. These results indicate that the NANC inhibitory neurotransmitter is not metabolized by enzymes susceptible to inhibition by aprotinin, leupeptin, soybean trypsin inhibitor, or thiorphan and, accordingly, distinguish NANC nervous responses from those induced by VIP. The results also suggest that the NANC excitatory system can interact functionally with the NANC inhibitory system, as evidenced by the blunting of NANC relaxation responses following inhibition of tachykinin metabolism and elimination of this effect by capsaicin. PMID- 2240835 TI - Effects of inflammatory mediators on the responsiveness of isolated human airways to methacholine. AB - Several studies have suggested that in asthmatics the quantities of inflammatory mediators such as histamine, thromboxane A2 (TxA2), prostaglandin D2 (PGD2), prostaglandin F2 alpha (PGF2 alpha), and leukotriene C4 (LTC4) that are present in the airway lumen are related to the degree of bronchial responsiveness to inhaled methacholine (MCh). Therefore, we studied the effect of these mediators on the cholinergic responsiveness of isolated human airway segments. Lung tissue collected at thoracotomy from 30 patients was studied. Dose-response curves to MCh were obtained from bronchial segments before, during, and after incubation with either a subthreshold or a threshold concentration of histamine (10(-10) or 10(-8) M), the stable TxA2 analogue U46619 (10(-11) or 10(-9) M), PGD2 (5 x 10( 9) or 5 x 10(-7) M), PGF2 alpha (10(-9) or 10(-7) M), or LTC4 (10(-11) or 10(-9) M). With the exception of LTC4, the presence of any of these mediators at either concentration increased the sensitivity to MCh by a factor of 1.1 to 2 (p less than 0.05, ANOVA). This increase did not depend on the dose of the mediator (p greater than 0.05, ANOVA). These data indicate that mediator-induced muscle hypersensitivity can explain a small part of the leftward shift of the dose response curve to inhaled MCh as observed in asthma. PMID- 2240836 TI - Bronchial responsiveness to histamine in infants and older children. AB - Normal infants have been shown to respond to a relatively low concentration of inhaled histamine. However, those studies used partial maximal expiratory flow volume (PMEFV) curves to assess lung function. In order to directly compare responsiveness between infants and older children, we compared bronchial responsiveness to histamine between a group of 45 normal infants, median age 4 wk (range 2 to 6 wk) and a group of 30 nonasthmatic older children, median age 10 yr (range 5 to 15 yr) using PMEFV curves in both groups to assess lung function. In the infant group, PMEFV curves were generated using the forced expiratory flow volume technique. For the older children, PMEFV curves were generated by voluntary effort. The provocative concentration of histamine that produced a 40% fall (PC40) in maximum flow at functional residual capacity (VmaxFRC) was calculated from the PMEFV curves. The geometric mean PC40 of the infants (1.02 g/L) was lower than the geometric mean of the older children (3.4 g/L) (p less than 0.001). However, these results were then corrected for dilution of the aerosol due to air entrainment (AE). Corrected values of PC40 were not significantly different between infants and older children. These results demonstrate the importance of accounting for AE in the evaluation of histamine responsiveness and suggest that bronchial responsiveness may be similar in normal infants and older children. PMID- 2240837 TI - Circadian basis of the late asthmatic response. AB - The late asthmatic response (LAR) to an allergen challenge has a marked impact on lung function in the patient with asthma. Virtually all studies on the LAR have been done during the daytime. This study evaluated the LAR as a function of the time of day an inhaled allergen challenge was performed. An allergen challenge given in the morning produced a LAR in 4 of 10 subjects, while the same challenge in the evening caused a LAR in 9 of 10 (p less than 0.05). The time to onset of the LAR following the morning and evening challenges was 9.4 +/- 2.0 h versus 3.1 +/- 0.3 h, respectively (p less than 0.05). The maximal decrease in FEV1 for the LAR was 32.8 +/- 5.6% for the morning challenge versus 43.0 +/- 3.1% in the evening (p less than 0.05). Additionally, the bronchial responsiveness to methacholine was significantly greater at 24 h following evening allergen challenge than after the morning (p less than 0.05) challenge. Thus, it is important to take into account the time of day a patient is exposed to an allergen in regard to the development of the LAR. PMID- 2240838 TI - Ozone concentration and pulmonary response relationships for 6.6-hour exposures with five hours of moderate exercise to 0.08, 0.10, and 0.12 ppm. AB - The magnitudes of pulmonary responses we previously observed (1) following 6.6-h exposures to 0.12 ppm ozone (O3) suggested that responses would also occur with similar exposures at lower O3 concentrations. The objective of this study was to determine the extent of pulmonary function decrements, respiratory discomfort, and increased airway reactivity to methacholine induced by exposure to O3 below 0.12 ppm. Separate 6.6-h chamber exposures to 0.00, 0.08, 0.10, and 0.12 ppm O3 included six 50-min periods of moderate exercise (VE approximately equal to 39 L/min, HR approximately equal to 115 bpm, and VO2 approximately equal to 1.5 L/min). Each exercise period was followed by 10 min of rest. A 35-min lunch break was included midway through the exposure. Although not intended as an exact simulation, the overall duration, intensity, and metabolic requirements of the exercise performed were representative of a day of moderate to heavy work or play. Preexposure FEV1 averaged 4.39 L, and essentially no change (+0.03 L) occurred with exposure to 0.00 ppm O3. Significant decreases (p less than 0.01) of -0.31, -0.30, and -0.54 L were observed with exposures to 0.08, 0.10, and 0.12 ppm, respectively. The provocative dose of methacholine required to increase airway resistance by 100% (PD100) was 58 cumulative inhalation units (CIU) following exposure to 0.00 ppm and was significantly reduced (p less than 0.01) to 37 CIU at 0.08, 31 CIU at 0.10, and 26 CIU at 0.12 ppm O3; reductions in PD100 are considered indicative of increases in nonspecific airway responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240839 TI - Biodistribution, tissue reaction, and lung retention of pentamidine aerosolized as three different salts. AB - Aerosolized pentamidine isoethionate is retained in the lung and appears to prevent Pneumocystis carinii pneumonia (PCP) in many AIDS patients. We evaluated alternative formulations of pentamidine that might reduce the airway irritation associated with aerosolized pentamidine isoethionate. Specifically, we assessed the biodistribution, histologic response, and lung retention of the isoethionate, gluconate, and lactate salts of pentamidine after aerosol administration to mice. For each of the three aerosolized salts tested, greater than 50% of the pentamidine initially recovered from the lungs after one dose was still retained there 14 days later. Thus, significant levels of pentamidine, aerosolized as three different salts, are retained in the lung for at least 2 wk after a single dose. The three salts of pentamidine each produced high lung to extrapulmonary drug ratios, the converse of that produced by intravenous injection of pentamidine isoethionate. At very high aerosol doses, the ability of the lung to retain pentamidine appeared saturable. Even aerosolized daily for 2 wk at very high doses, none of the three pentamidine salts produced histologic evidence of organ toxicity. A Phase 1 trial of aerosolized pentamidine gluconate in AIDS-PCP patients is now in progress to determine if this approach can reduce airway irritation. PMID- 2240840 TI - Respiratory health effects of the indoor environment in a population of Dutch children. AB - The effect of indoor exposure to nitrogen dioxide on respiratory health was studied over a period of 2 yr in a population of nonsmoking Dutch children 6 to 12 yr of age. Lung function was measured at the schools, and information on respiratory symptoms was collected from a self-administered questionnaire completed by the parents of the children. Nitrogen dioxide was measured in the homes of all children with Palmes' diffusion tubes. In addition, information on smoking and dampness in the home was collected by questionnaire. There was no relationship between exposure to nitrogen dioxide in the home and respiratory symptoms. Respiratory symptoms were found to be associated with exposure to tobacco smoke and home dampness. There was a weak, negative association between maximal midexpiratory flow (MMEF) and exposure to nitrogen dioxide. FEV1, peak expiratory flow, and MMEF were all negatively associated with exposure to tobacco smoke. Home dampness was not associated with pulmonary function. Lung function growth, measured over a period of 2 yr, was not consistently associated with any of the indoor exposure variables. The development of respiratory symptoms over time was not associated with indoor exposure to nitrogen dioxide. There was a significant association between exposure to environmental tobacco smoke in the home and the development of wheeze. There was also a significant association between home dampness and the development of cough. PMID- 2240841 TI - Pulmonary fibrosis in aluminum oxide workers. Investigation of nine workers, with pathologic examination and microanalysis in three of them. AB - Epidemiologic surveys have indicated an excess of nonmalignant respiratory disease in workers exposed to aluminum oxide (Al2O3) during abrasives production. However, clinical, roentgenographic, histologic, and microanalytic description of these workers are lacking. This is a report of nine Al2O3-exposed workers with abnormal chest roentgenograms (profusion greater than or equal to 1/0, ILO/UC) from a plant engaged in the production of Al2O3 abrasives from alundum ore. Mean duration of exposure was 25 yr, and time since first exposure was 28 yr. in a subgroup of three, the severity of symptoms, reduction in the forced vital capacity (67% predicted) and diffusing capacity (51% predicted), and progressive roentgenographic changes (profusion greater than or equal to 2/2) prompted open lung biopsy. Lung tissue was analyzed by scanning electron microscopy and electron microprobe analysis. In each of the three biopsies, interstitial fibrosis with honeycombing was seen on routine section. In one biopsy, silica and asbestos fiber counts were at the low end of the range seen with silicosis and asbestosis; however, the absence of asbestos bodies and silicotic nodules suggested that the fibrosis was due to another cause. Metals occurred in amounts several orders of magnitude above background, and the majority was aluminum as Al2O3 and aluminum alloys. The findings in these nine workers suggests a common exposure as the possible cause. The nonspecific pathologic findings, absence of asbestos bodies and silicotic nodules, and the striking number of aluminum containing particles suggest that Al2O3 is that common exposure. The possibility of "mixed dust" fibrosis should also be considered. PMID- 2240842 TI - Molecular analysis of the heterogeneity among the P-family of alpha-1-antitrypsin alleles. AB - The rare P-family of alpha 1-antitrypsin (alpha 1AT) variants is defined by the position of migration of the alpha 1AT protein on isoelectric focusing of serum (IEF) between the common M and S variants. To begin to examine the molecular heterogeneity among the P-type alleles, two unrelated subjects and their families identified by IEF to be carrying a P allele were analyzed. The first, Plowell, is a deficiency allele associated with reduced serum alpha 1AT levels, and the second, Psaint albans, is associated with normal serum levels. DNA sequence analysis of Plowell, the more anodal of the two variants on IEF analysis, showed that if differed from the normal M1(Val213) allele by a single base and amino acid substitution Asp256 GAT----Val GTT. In contrast, Psaint albans, a slightly more cathodally positioned variant on IEF analysis, differed from the coding exons of the normal M1(Val213) allele by two mutations, Asp341 GAC----Asn AAC, and a silent substitution in the same codon as the Plowell variant, Asp256 GAT--- Asp GAC. Evaluation of Plowell mRNA transcripts by Northern and cytoblot analyses demonstrated they were of normal size and amount, and Plowell mRNA transcripts could be translated normally in vitro. Retroviral insertion of the Plowell cDNA into the genome of 3T3 fibroblasts demonstrated that it directed the synthesis of alpha 1AT, but at levels 24% that of the Psaint albans cDNA or the normal M1 (Val213) cDNA, with a pattern of biosynthesis consistent with the concept that the Plowell alpha 1AT deficiency state results from intracellular degradation of the newly synthesized Plowell protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240843 TI - Phospholipase A2-induced pulmonary and hemodynamic responses in the guinea pig. Effects of enzyme inhibitors and mediators antagonists. AB - The effect of phospholipase A2 (Naja naja) PLA2) on mean arterial blood pressure and intratracheal pressure was examined in anesthetized guinea pigs. Intracheally administered PLA2 (1 to 10 U) produced acute, dose-dependent increases in mean arterial blood pressure and intracheal pressure. However, Intravenously administered PLA2 (doses as large as 1,000 U) did not alter monitored variables. Acute PLA2-induced morphologic alterations were characterized by airway constriction, airway/alveolar cell damage, and pulmonary sequestration of both leukocytes and platelets. PLA2-induced increases in both mean arterial blood pressure and intratracheal pressure were attenuated to varying degrees by pretreating intravenously with indomethacin (10 mg/kg), a cyclooxygenase inhibitor, and WEB 2086 (0.1 mg/kg), a platelet-activating factor antagonist. Both ICI 198,615 (1 mg/kg), a leukotriene D4, receptor antagonist given intravenously, and dexamethasone (50 mg/kg), a steroidal anti-inflammatory agent given intraperitoneally as a 2-day pretreatment, reduced PLA2-induced increases in intratracheal pressure. Pyrilamine (2 mg/kg), a histamine1-receptor antagonist given intravenously, did not modify PLA2-induced pathophysiologic responses. Guinea pigs exposed to aerosolized PLA2 (100 U/ml) exhibited evidence of increased bronchoalveolar lavage macrophage, leukocyte, and lymphocyte accumulation at 24 h post-PLA2. These studies suggest that in vivo PLA2-induced pathophysiologic changes in the guinea pig involve alterations in resident airway cell populations as well as sequestration and infiltration of inflammatory cells. Both eicosanoids and platelet-activating factor appear to contribute to these PLA2-induced pathophysiologic effects. PMID- 2240844 TI - Computerized tomography in the evaluation of allergic bronchopulmonary aspergillosis. AB - Allergic bronchopulmonary aspergillosis (ABPA) is a destructive disease of the lung characteristically associated with central bronchiectasis. This study was designed to determine if high-resolution computerized tomography (CT) could be used to define bronchiectasis in patients with suspected disease. Sixteen patients with asthma were studied. All demonstrated immediate cutaneous reactivity to common aeroallergens including Aspergillus fumigatus. Eight patients had clinical and immunologic evidence of ABPA. Six to 12 high-resolution CT sections (1.5 mm) were obtained at 1- to 2-cm intervals from the aortic knob to the dome of the diaphragm. All radiographs were evaluated separately by two readers in a blinded fashion and graded as to the presence and type of bronchial dilatation and bronchial wall thickening. Bronchial dilatation was seen in 41% of lung lobes in the ABPA group compared to 15% in the non-ABPA asthmatic control group. Upper lobe involvement and bronchial wall thickening was common to both groups. The presence of bronchiectasis in the control group may indicate that asthma is a more destructive lung disease than is currently appreciated. High resolution CT of the chest has been shown in previous studies to have a sensitivity and specificity approaching that of bronchography, and the current findings support its use in the detection of bronchiectasis in patients with asthma suspected of having ABPA. PMID- 2240845 TI - Computed tomography of chronic diffuse infiltrative lung disease. Part 1. PMID- 2240846 TI - Pulmonary histiocytosis X with mediastinal lymph node involvement. AB - In this report, we describe a patient with the classic histology of pulmonary histiocytosis X, who had bilateral reticulonodular densities and mediastinal lymph node involvement. The diagnosis was confirmed by the use of electron microscopy and immunohistochemical markers (PS100, HLA-DR, and CD1), which allowed us to recognize the lymph node infiltration of X histiocytes. An association of mediastinal lymph node enlargement with pulmonary histiocytosis X has been reported but it has never been histologically documented. PMID- 2240847 TI - Dissecting aneurysm of the pulmonary artery with pulmonary hypertension. AB - Pulmonary artery dissection was observed in a 64-yr-old female patient with severe pulmonary hypertension, which was probably primary (pulmonary vascular resistance, 817 dyn.s.cm-5; normal range less than or equal to 200 dyn.s.cm-5). The patient was admitted to the hospital because of severe dyspnea on exertion. Echocardiography demonstrated a dissecting aneurysm of the pulmonary artery. Right heart catheterization revealed severe pulmonary hypertension (mean pulmonary artery pressure, 64 mm Hg; normal range, 10 to 22 mm Hg); dissection of the pulmonary artery was confirmed by pulmonary arteriography. One-year follow-up was uneventful. In the literature, 28 patients with dissecting aneurysm of the pulmonary artery are reviewed. The dissection has only been diagnosed in life in one patient (by echocardiography). PMID- 2240849 TI - Colobronchial fistula: a rare complication of Crohn's colitis. AB - A 29-yr-old white woman presented with chronic pneumonia in the left lower lobe and with left pleural effusion. She was known to have inflammatory bowel disease, but she was asymptomatic under maintenance treatment with 5-ASA. She received numerous antibiotic regimens according to susceptibility testing of microorganisms cultured from sputum and bronchial lavage and on an empiric basis was also given antituberculosis treatment, but there was no clinical improvement or change in the chest radiographic findings. Sputum was repeatedly examined and yielded, among other organisms, Clostridium inocuum, Enterobacter, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus aureus. On one microscopic examination of sputum, the presence of feculent material was suspected. A subsequent gastrografin enema revealed a cologastric and colobronchial fistula between the splenic flexture of the colon and the greater curve of the stomach and the bronchial system. Segmental resection of the colon and resection of the lower lobe of the left lung were performed. Histologic findings of the resected colon were consistent with Crohn's disease. After a long period of postoperative recovery, the patient returned to good general health and well-being. To our knowledge, a colobronchial fistula caused by Crohn's colitis has not been previously reported. PMID- 2240848 TI - Flexible bronchoscopic removal of radioccult polyurethane foam, with pneumonitis in a hyperventilated lobe. AB - An intellectually delayed adult ingested and aspirated a large quantity of polyurethane foam, developing acute respiratory failure in association with partial airway obstruction. The foam was identified by flexible bronchoscopy and successfully removed from the bronchus intermedius and left mainstem bronchus with a retrieval basket. This facilitated normalization of blood gases and eventual recovery. However, the unobstructed right upper lobe became infiltrated radiographically, presumably resulting from regional hyperinflation and/or occult focal aspiration. PMID- 2240850 TI - The rise of tuberculosis in America before 1820. AB - Bills of mortality, newspaper and gazette articles, journals, and other records with specific references to "consumption," "phthisis," and other terms for tuberculosis were reviewed to determine the occurrence and importance of tuberculosis in the American colonies before 1820. Review of these sources indicates a marked increase in the proportional mortality from tuberculosis in the United States in the 18th century. "Consumption" may have been the leading cause of death in adult American colonists. PMID- 2240851 TI - Cytokines of the lung. PMID- 2240852 TI - The 1990 Report of the Surgeon General: The Health Benefits of Smoking Cessation. PMID- 2240853 TI - Six-month isoniazid-rifampin treatment for pulmonary tuberculosis in children. AB - One hundred and seventeen children with pulmonary tuberculosis underwent treatment with a 6-month daily regimen of rifampin (15 mg/kg/day) and isoniazid (10 mg/kg/day). The criteria for the diagnosis of pulmonary tuberculosis were (1) clinical symptoms and signs in 93 children (79%), (2) history of direct contact with an adult with tuberculosis in 106 children (91%), (3) tuberculin reaction of 5 mm or more, without previous bacillus Calmette-Guerin (BCG), in 45 children (38%), (4) suggestive radiologic alterations in all patients, and (5) positive bacteriology or histology in four patients (3%). The treatment was completed by 97 children (83%). The mean weight gain during therapy was 2,145 g. There was an excellent clinicoradiologic response to the treatment, and improvement in chest roentgenograms was observed in all patients at the end of therapy. No relapses occurred among the patients followed for an average of 21.4 months. This study indicates that the treatment of primary pulmonary tuberculosis in children with a combination of rifampin and isoniazid daily for 6 months is efficacious and does not result in any relapse. PMID- 2240854 TI - Human intestinal tissue antibiotic concentrations. Clindamycin, gentamicin, and mezlocillin. AB - An antibiotic, to be effective for prophylaxis in abdominal trauma, should quickly achieve high concentrations in the intestinal wall and at enough inhibitory levels to kill most aerobic and anaerobic bacteria that are potential contaminants at the site of surgical incision. Therefore, we studied the intestinal tissue levels of clindamycin, gentamicin, and mezlocillin to see whether the tissue levels achieved by these antibiotics in the intestinal tissue were adequate. A single dose of mezlocillin, 4 grams; clindamycin, 600 mg and gentamicin, 80 mg; quickly reached the desired concentrations, i.e., 52.3, 9.69 and 6.1 micrograms/gram of intestinal tissue respectively. These levels were high enough to inhibit the growth of most isolates of E. coli and B. fragilis, common pathogens involved in intra-abdominal abscess. PMID- 2240855 TI - Ponderal index as a predictor of postoperative complications. AB - Four hundred sixty-eight patients undergoing elective surgery were prospectively followed for the development of postoperative complications. There was a trend toward increasing complication rate with a lower ponderal index. However, lower ponderal indices were associated with increasing rates of diabetes mellitus and hypertension. Of these patients, forty cases with postoperative complications were matched to 40 control cases for sex, age, concomitant illness and operation performed. The cases of postoperative complications had a statistically significantly lower ponderal index than the controls (11.98 versus 12.43). The increased risk of postoperative complications in those patients with a ponderal index of less than 11 was 3.36, and less than 13 was 3.44. Surgeons who treated patients with lower ponderal indices need to have a high index of suspicion for the development of postoperative complications in these patients. PMID- 2240856 TI - Gastroesophageal reflux and sclerotherapy strictures. AB - The development of esophageal stricture is common following endoscopic variceal sclerotherapy (EVS). Gastroesophageal reflux may be at least partly responsible. Twelve randomly selected male patients underwent chronic EVS for the management of bleeding esophageal varices. Six patients developed strictures during or after EVS, six did not. There were no significant differences between stricture and nonstricture patients during 24 hour esophageal pH monitoring. Three of the six stricture patients and four of the six nonstricture patients had an abnormal amount of reflux. Gastroesophageal reflux occurs frequently in patients undergoing EVS, and it is not likely to play a major role in EVS stricture formation. PMID- 2240857 TI - The inactivation of antithrombin III by serum elastase in patients with surgical infections. AB - The relationship between serum elastase and antithrombin III was determined in septic surgical patients as a possible mechanism for intravascular thrombosis and hypercoagulability during sepsis. Eighteen patients with surgical infections and elevated white blood cell counts had their blood assayed daily for white blood cell count, serum elastase, and antithrombin III, until the patient's white blood cell count returned to normal. Antithrombin III was significantly lower (0.87%) when elastase was above the normal range (greater than 14.2 micrograms/ml). Elastase was significantly higher (30.6 micrograms/ml), when antithrombin III was less than normal. These data indicate that elevated serum elastase is associated with a significant reduction in circulating antithrombin III. Stimuli that increase serum elastase, i.e. surgery, trauma, or sepsis may promote intravascular thrombosis by the inhibition of antithrombin III at the blood endothelial cell interface. PMID- 2240858 TI - Nonsurgical management of breast infections in nonlactating women. A word of caution. AB - Management options for infectious mastitis have traditionally been limited to surgical drainage. With the advent of percutaneous fine needle aspiration (FNA), nonoperative treatment may be an alternative, though criteria for use have not been defined. During a 30-month period, 22 women presented with breast infection. Treatment was instituted based upon the clinical stage of infection. Patients with cellulitis (n = 8) were managed with diagnostic FNA/antibiotics. Those with focal abscess (n = 10) underwent FNA of the cavity/antibiotics. Patients with multiloculated abscess (n C = 3) underwent urgent surgical drainage. Of the 19 patients initially treated nonoperatively, resolution occurred in nine (47%); stage of infection did not effect outcome. Surgical drainage was required in the remainder; two cancers were found. FNA cytology in these (and all) patients was negative for malignancy. All underwent mammography during treatment. In 17 (77%) cancer was considered of low probability. The only patient with a mammogram highly suspicious for cancer had fat necrosis on biopsy. Bacterial cultures were positive in 79 per cent, virtually all with Gram (+) cocci. Four patients harbored Gram (-) organisms as well, two in concert with breast cancer. CONCLUSIONS: 1) select breast infections can be successfully managed nonoperatively, 2) the accuracy of FNA and mammography in the diagnosis of breast cancer may be impaired by coincident infection, 3) the finding of a Gram (-) breast infection warrants abandonment of nonoperative management in favor of tissue confirmation of the disease process. PMID- 2240859 TI - Starch peritonitis. A case report and clinicopathologic review. AB - A case of starch peritonitis is presented with a review of the history of this continuing problem. The syndrome's presentation, diagnosis, histopathology and treatment are discussed. The rarity of starch peritonitis today may be due to more attention to glove washing by surgeons, fewer impurities in the glove powder or lack of recognition of the syndrome. In order to prevent a resurgence of the starch peritonitis syndrome we must continue to emphasize the importance of washing gloves, maintain the quality control and purity of the powder used, and be cognizant of the signs and symptoms so that such cases may be managed nonoperatively. PMID- 2240860 TI - Cecal diverticulitis presented as a cecal tumor. AB - Seven patients diagnosed as having acute appendicitis were operated on and a cecal wall mass due to cecal diverticulitis was found. In two patients the mass could not be separated from the cecal wall and right colectomy was performed. In five patients, in whom the mass could be separated from the cecum, conservative operations (three diverticulectomies and two wedge resections) were performed, thus avoiding needless, more extensive surgery. PMID- 2240861 TI - Intra-abdominal abscesses in Crohn's disease. AB - We reviewed 22 patients who had intra-abdominal abscesses secondary to Crohn's disease. A total of 29 abscesses were discovered. These included superficial and deep intraperitoneal as well as pelvic and retroperitoneal abscesses. Diagnosis was aided by ultrasound and computer tomographic scanning. Barium studies continue to play an important role in delineating the extent of bowel involvement and fistulization. Treatment varied depending on the location and size of the abscess. The need for ultimate bowel resection was determined in the majority of cases by the presence of fistulization between the abscess cavity and the bowel. The terminal ileum or neoterminal ileum were almost always involved. PMID- 2240862 TI - An objective appraisal of the role of computed tomographic (CT) guided drainage of intra-abdominal abscesses. AB - Computed tomographic (CT) guided drainage is an important tool in the treatment of intra-abdominal abscess. Its most important role is in the treatment of small, unilocular, well-placed abscesses. Success rates in our experience diminish considerably in abscesses involving necrotic tumors or those infected with yeast. As is frequently characteristic of new technologic procedures, the initial evaluation of the success rate of the procedure is overly optimistic. The procedure carries a considerable complication rate (13%) and mortality rate (15%). Most importantly, success is usually evident early; within the first 24 to 48 hours. After this length of time, careful evaluation to consider further treatment should be contemplated. PMID- 2240863 TI - Association of acute colonic pseudo-obstruction (Ogilvie's syndrome) with herpes zoster. AB - Ogilvie's syndrome, or acute pseudo-obstruction of the colon is characterized by massive distension of the colon in the absence of organic distal obstruction. The syndrome is associated with various unrelated and, most often, extra-abdominal causes. An association between Ogilvie's syndrome and herpes zoster has been reported only once, by Ceccese et al. in 1985. We present a second such case. This patient did not show evidence of any active illness other than the involvement of the T10 dermatome by herpes zoster. The patient's symptoms of colonic obstruction subsided with resolution of the zosteriform rash. PMID- 2240865 TI - Jejunal-rectal fistula as a complication of postoperative radiotherapy. AB - We present the case of a patient with an unusual, complex enteric fistula with multiple tracts and associated abscesses. The fistula was a late complication of radiotherapy, administered three years earlier, after resection for carcinoma of the sigmoid colon. Most of the small bowel was involved in the radiation-induced disease. A wide resection was performed successfully. This report reviews current literature on intra-abdominal postradiotherapy injuries, particularly intestinal fistulae. PMID- 2240864 TI - Porta hepatis disruption from blunt trauma. AB - Extrahepatic porta hepatis injuries from blunt abdominal trauma are exceedingly rare; all recently reported cases involve disruption of the common bile duct at its intrapancreatic portion. We herein report a patient with lacerations of the proper hepatic artery and bile duct occurring from deceleration/torsion of the porta hepatis after high speed vehicular collision. PMID- 2240866 TI - Obstructing paraduodenal hematoma. PMID- 2240867 TI - Femoral arteriovenous fistula as a complication of percutaneous transluminal coronary angioplasty. A report of five cases. AB - Arteriovenous fistula (AVF) associated with invasive and diagnostic angiographic procedures is rare. The incidence is increased with procedures such as percutaneous transluminal coronary angioplasty (PTCA) but is still quite low. We report five cases of AVF within a 17-month period, representing 0.15 per cent of all cardiac catheterizations and 0.87 per cent of PTCAs. All five patients presented with groin bruits. There were two associated pseudoaneurysms and one patient with deep vein thrombosis. All patients underwent uneventful division of the fistula. A thorough understanding of the anatomy of the femoral triangle is necessary in order to avoid this complication. That all fistulas were in the superficial or profunda femoris arteries emphasizes the importance of avoiding a low groin puncture. Early angiography and surgical intervention are recommended for optimal results. PMID- 2240869 TI - Lower extremity revascularization via the lateral plantar artery. AB - Lower extremity bypass grafts to the tibial and crural arteries are commonly employed to treat patients with atherosclerotic limb-threatening ischemia. Although occasional series have mentioned bypasses to a plantar artery, few of these specifically examine the results of arterial reconstructions using these vessels. Six patients underwent femoral to lateral plantar artery (LPA) bypass within a 19-month period for gangrene of the forefoot. There was one early graft failure and in the five completely autogenous reconstructions, graft patency and limb salvage had been achieved during a follow-up ranging from three to 22 months. The LPA is an acceptable site for anastomosis of lower extremity bypass grafts and the early results presented herein support its more liberal use when proximal sites are unavailable. PMID- 2240868 TI - The role of endoscopic retrograde pancreatography (ERP) in blunt abdominal trauma. AB - The diagnosis of pancreatic injury is often difficult because it lies retroperitoneally in a protected area. Delayed diagnosis and treatment of blunt pancreatic trauma can result in significant morbidity and mortality. Endoscopic Retrograde Pancreatography (ERP) is infrequently used in the diagnosis of pancreatic injury. We reviewed our experience with the use of ERP in patients with blunt pancreatic injury. Two stable patients with traumatic pancreatitis underwent ERP shortly after injury. CT scans revealed a transverse fracture of the distal pancrease in one and fluid accumulation in the other around the pancreas extending to the right kidney and left hepatic lobe. The absence of ductal disruption on ERP allowed nonoperative management of the pancreatitis. Resolution was documented by the absence of symptoms on regular oral intake, normal serum amylase levels, and normal follow-up CT scans. A third patient with persistent fistulae three months postinjury underwent preoperative ERP revealing ductal obstruction. This facilitated the planning of a distal pancreatectomy and subsequently the fistulae healed. A fourth patient underwent an exploratory laparotomy on the basis of clinical and CT scan findings that could have been circumvented with preoperative ERP. ERP in selected patients allows nonoperative treatment in the absence of ductal injury or earlier operative treatment of ductal injury. It also aids the treatment of late complications by delineating ductal anatomy. PMID- 2240870 TI - Normal angiograms and carotid pathology. AB - Nonstenotic ulcerated atherosclerotic plaques of the carotid arteries may be associated with symptoms of transient ischemic attacks, amaurosis fugax, and stroke. Preoperative evaluation of patients with these symptoms has traditionally included ultrasound and arch aortography angiograms of the area of the carotid bifurcation. Recent evidence has shown that ultrasound is more accurate in detection and morphologic delineation of these nonstenotic lesions. We analyzed the hospital records of 21 patients with ultrasonographic evidence of disease in whom arteriograms were negative. The patient group comprised 15 men and six women, with an average of 66 years. All patients had symptoms of hemispheric transient ischemic attacks and were evaluated with B-mode ultrasound and arteriography. Ultrasound was positive and arteriogram "negative" in all of the patients (i.e., described by the radiologist as without hemodynamic significant disease or ulceration, or as normal). The ultrasound diagnosis was confirmed at operation with findings of 20 to 50 per cent stenosis and ulcerative plaques. At retrospective review of the arteriograms, three ulcerations were found in the 21 patients. We conclude that B-mode ultrasound better defines nonstenotic ulcerative lesions and decisions to perform carotid endarterectomy may be based on either positive test. An ulcerative plaque by B-mode ultrasound and appropriate symptoms, therefore, may not require angiography before operation. PMID- 2240871 TI - Endoscopic extraction of an entrapped nasogastric tube. AB - Inadvertent entrapment of a nasogastric tube within a stapled gastrointestinal anastomosis is a preventable and infrequent surgical complication. We report our experience with this complication and describe a successful endoscopic approach to management. PMID- 2240872 TI - Management of premature removal of the percutaneous gastrostomy. AB - Percutaneous endoscopic gastrostomy (PEG) has become the preferred method of enteral access for nutritional support. With increased use of this modality, complications are encountered more frequently. Premature withdrawal, inadvertent removal of the gastrostomy tube within the first seven days after insertion, before adherence of the gastric serosa to the parietal peritoneum, has been an indication for laparotomy. This report describes the treatment of premature withdrawal by immediate endoscopic replacement. Over an 18-month period, 271 patients underwent insertion of a PEG. Five patients (1.8%) who inadvertently removed their gastrostomy tube within seven days of insertion were treated with immediate replacement using the retrograde string technique, avoiding laparotomy. All five PEGs were successfully replaced through the same gastrostomy site. Despite the presence of pneumoperitoneum, no patient developed peritonitis or other septic complications. Premature gastrostomy tube withdrawal is safely managed by endoscopic replacement and observation. Laparotomy is unnecessary and potentially meddlesome. PMID- 2240873 TI - Transmission of human immunodeficiency virus type 1 (HIV-1) by exposure to blood: defining the risk. PMID- 2240874 TI - Management of small abdominal aortic aneurysms. PMID- 2240875 TI - Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations. AB - OBJECTIVE: To assess the incidence of human immunodeficiency virus type 1(HIV-1) transmission by antibody (anti-HIV-1)-positive blood components, and to determine the immunologic and clinical course in HIV-1-infected recipients. DESIGN AND SUBJECTS: We retrospectively tested approximately 200,000 donor blood component specimens stored in late 1984 and 1985 for anti-HIV-1, and we contacted recipients of positive specimens to determine their serologic status. They were compared with both recipients of HIV-1-negative transfusions and healthy (untransfused) controls. Subjects were seen at 3- to 6-month intervals for up to 4 years for clinical and immunologic evaluations. MEASUREMENTS AND MAIN RESULTS: Of 133 recipients, 9 had other possible exposures. Excluding these cases, 111 of 124 (89.5%) were anti-HIV-1-positive (95% CI, 84.1% to 94.5%). The recipient's sex, age, underlying condition, and type of component did not influence infection rates. The cumulative risk for developing the acquired immunodeficiency syndrome (AIDS) within 38 months after transfusion was 13% (CI, 7.5% to 21.6%). At 36 +/- 3 months after the index transfusion, seropositive recipients had lower counts of CD2+CDw26+, CD4+, CD4+CD29+, and CD4+CD45RA+subsets and more CD8+I2+ lymphocytes than did recipients of anti-HIV-1-negative transfusions. The CD4+ and CD2+CDw26+subsets changed the most rapidly. The absolute CD8+ count remained normal. CONCLUSIONS: Transfusion of anti-HIV-1-positive blood infected 90% of recipients. The rate of progression to AIDS within the first 38 months after infection was similar to that reported for homosexual men and hemophiliacs. Although most lymphocyte subset counts changed over time, CD8+ counts were constant. PMID- 2240876 TI - Risk for occupational transmission of human immunodeficiency virus type 1 (HIV-1) associated with clinical exposures. A prospective evaluation. AB - OBJECTIVES: To summarize the results of a 6-year, ongoing, prospective study of the risk for human immunodeficiency virus type 1 (HIV-1) transmission among health care workers, and to estimate the magnitude of the risk for HIV-1 infection associated with different types of occupational exposures. DESIGN: Prospective cohort study; the median follow-up for employees sustaining parenteral exposures was 30.2 months (range, 6 to 69 months). SUBJECTS: Health care workers at the Clinical Center, National Institutes of Health, including those reporting parenteral and nonparenteral occupational exposures to HIV-1. MEASUREMENTS AND MAIN RESULTS: One thousand three hundred and forty-four clinical health care workers reported 179 percutaneous and 346 mucous membrane exposures to fluids from HIV-1-infected patients during a 6-year period. Responding to a supplementary questionnaire, 559 of these workers reported 2712 cutaneous exposures to blood from HIV-1-infected patients and more than 10,000 cutaneous exposures to blood from all patients during a 12-month period. Occupational transmission of HIV-1 occurred in a single worker after a parenteral exposure to blood from an HIV-1-infected patient. No infections occurred after either mucous membrane or cutaneous exposures to blood from HIV-1-infected patients. Use of newer diagnostic technologies (for example, antigen detection, gene amplification) has not resulted in the identification of occupationally transmitted seronegative infections. CONCLUSIONS: Combining our results with those of other prospective studies, the risk for HIV-1 transmission associated with a percutaneous exposure to blood from an HIV-1-infected patient is approximately 0.3% per exposure (95% CI, 0.13% to 0.70%); the risks associated with occupational mucous membrane and cutaneous exposures are likely to be substantially smaller. These data support the use of barrier precautions and suggest a need for strategies that change health care providers' attitudes and behaviors. PMID- 2240877 TI - Carotid endarterectomy for elderly patients: predicting complications. AB - OBJECTIVE: To determine whether the complication or death rate from carotid endarterectomy can be predicted from hospital and physician structural variables, such as the hospital's teaching status or the number of endarterectomies done by the surgeon per year. DESIGN: Survey of medical records. After controlling for the severity of the patient's condition on the basis of data in the medical record at the time of the endarterectomy, regression analyses were used to predict the postoperative stroke, heart attack, and 30-day death rate as a function of patient, physician, and hospital characteristics. SETTING: Three geographic areas (states or large parts of states; average population, 3 million) in the United States. PATIENTS: Random sample of 1302 patients 65 years of age or older having carotid endarterectomy in 1981. INTERVENTION: Carotid endarterectomy. MEASUREMENTS AND MAIN RESULTS: Of 1302 patients, 11.3% had a postoperative stroke or heart attack or died within 30 days of the operation. Patient age, race, income, and gender; physician volume, board certification status, and age; and hospital size, for-profit status, ownership, and teaching status were not significantly related to the postoperative complication or death rate. If the surgeon was a graduate of a foreign, but not a Western European or Canadian, medical school, however, the average complication or death rate rose from 10.4% to 19.6% (P less than 0.05). CONCLUSIONS: The effectiveness of carotid endarterectomy depends heavily on its complication rate. Because complications after surgery cannot, in general, be predicted from structural variables, referring physicians cannot rely solely on the surgeon's experience and qualifications when recommending a carotid endarterectomy. The surgeon's and the hospital's actual postoperative complication and death rate should be considered. PMID- 2240878 TI - Risk for colon adenomas in patients with rectosigmoid hyperplastic polyps. AB - OBJECTIVE: To determine whether hyperplastic polyps found in the rectosigmoid area of the colon are associated with proximal adenomas, and to judge whether patients with distal hyperplastic polyps found during sigmoidoscopy might benefit from full colonoscopy. DESIGN: Data on patients having colonoscopy collected prospectively according to a set protocol. The size and location of all polyps were noted, and all polyps were biopsied. SETTING: Two university hospitals. PATIENTS: One thousand eight hundred and thirty-six consecutive patients referred for colonoscopy between 31 December 1987 and 31 August 1989. RESULTS: Of the 970 patients who met eligibility requirements, 274 (28.3%) had adenomas and 108 (11.1%) had hyperplastic polyps. The proportion of patients with distal hyperplastic polyps and proximal adenomas (31.9%) was similar to the proportion of those without distal hyperplastic polyps (23.0%) (crude odds ratio, 1.57; 95% CI, 0.77 to 3.06). After adjusting for age and sex, the results were unchanged (adjusted odds ratio, 1.53; CI, 0.82 to 2.88). Patients with distal adenomas, on the other hand, were three times more likely to have proximal adenomas than those without distal adenomas (adjusted odds ratio, 3.42; CI, 1.99 to 5.88). CONCLUSIONS: Distal hyperplastic polyps are not strong predictors of risk for proximal adenomas. Based on the magnitude of the risk difference, we do not believe that finding a hyperplastic polyp during sigmoidoscopy justifies doing a full colonoscopy to search for proximal adenomas. Because rectosigmoid adenomas are associated with proximal adenomas, however, small polyps seen during sigmoidoscopy should be biopsied to determine their type. Colonoscopy should be reserved for patients who are proved to have adenomas. PMID- 2240879 TI - The internist in the management of head and neck cancer. AB - The general internist has an important role in the management of head and neck squamous cell cancers. This heterogeneous group of cancers must be accurately diagnosed and staged before planning treatment. Curability is directly related to stage at presentation and, because most patients with such cancers present to internists first, these physicians must be familiar with presenting symptoms and must be suspicious enough to refer patients with symptoms for appropriate evaluation. The work-up of patients with suspected unknown primary cancer presenting as adenopathy is detailed, and the physician is cautioned not to immediately proceed to open biopsy. As many as 10% of such primary cancers remain undetected, although, with proper therapy, the 5-year survival rate for squamous cell cancer of the head and neck is 60%. Those patients cured of head and neck cancer still face significant psychosocial and medical problems, including hypothyroidism, xerostomia, and a 20% rate of second primary cancer. Head and neck cancer is highly preventable; 75% of cases are related to tobacco and alcohol use. Smokeless tobacco has gained popularity among young Americans and is associated with an increased incidence of head and neck cancer at several sites. Education is crucial, and internists must seek strategies to stop patients from using tobacco products. Other etiologic factors include industrial carcinogens, Epstein-Barr virus, and diet. Retrospective serologic and dietary recall studies of vitamin A suggest an etiologic role of diet; vitamin A analogs have been tested in preneoplastic lesions. To reduce mortality from head and neck cancers, the general internist must play a central role in prevention and early detection. PMID- 2240880 TI - Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. AB - PURPOSE: To examine studies of normal colon and colorectal cancer for evidence that the location of the primary tumor proximal or distal to the splenic flexure of the colon may determine distinct genetic categories of this disease. DATA IDENTIFICATION: Studies were identified through a manual search of journals, through MEDLINE, and through review of bibliographies in identified articles. STUDY SELECTION: Approximately 300 articles were examined. About 150 articles were excluded because tumor location was not reported or was reported in a way that did not permit correlation with results or conclusions. DATA EXTRACTION: Articles were selected either because the presentation of data permitted correlation of results with anatomic regions of the colon or because they were relevant to inherited colorectal cancer. RESULTS OF THE ANALYSIS: Differences were noted in biologic properties of proximal and distal segments of normal fetal and adult colonic epithelium and in the epidemiologic, pathologic, cytogenetic, and molecular features of proximal and distal colorectal cancer. Some differences correlated with the features of inherited colorectal cancer (proximal, nonpolyposis or distal, and polyposis forms). CONCLUSIONS: Developmental and biologic differences in proximal and distal colon may reflect differing susceptibilities to neoplastic transformation. Differences in proximal and distal colorectal cancer suggest that each may arise through different pathogenetic mechanisms. Proximal tumors appear to represent a genetically more stable form of the disease and may arise through the same mechanisms that underlie inherited nonpolyposis colon cancer. Distal tumors show evidence of greater genetic instability and may develop through the same mechanisms that underlie polyposis associated colorectal cancer syndromes. PMID- 2240881 TI - Guidelines for the physician expert witness. American College of Physicians. AB - Editorial Note: The Clinical Practice Subcommittee of the College's Health and Public Policy Committee undertook development of "Guidelines for the Physician Expert Witness" in order to encourage broad physician participation in providing this much-needed assistance to the legal system. The College believes that more physicians should serve as experts as a component of their professional activities in order to meet the need for medical testimony rather than a few physicians with little current involvement in patient care spending disproportionate amounts of time testifying. The guidelines, adapted from the "Statement on Qualifications and Guidelines for the Physician Expert Witness" by the Council of Medical Specialty Societies (20 March 1989), recommend qualifications for experts and give general guidance. PMID- 2240882 TI - Economic incentives for ethical and courteous behavior in medicine. A proposal. AB - Several current and proposed structural features of medical reimbursement are intended to alter the behavior of health care providers. I propose adding a structure to make physician behavior more ethical. The structure's design would be complex, but its core would be reminiscent of how a patron tips waiters. My proposal would apply the truism that society's reward systems should foster rather than undermine social goals. This idea draws on features of medicine's social background and on a theory of behavior. It challenges the taboo against the physician's financial interests being clearly present in the doctor-patient relationship and it challenges the overly pure characterization of medical ethical dilemmas that currently dominates. Detailed sketches of necessary mechanisms, such as anonymous forms for patients to complete, are offered, and connections to the insights of George Bernard Shaw are made. PMID- 2240883 TI - Rewarding medicine: good doctors and good behavior. AB - Many patients think that there are shortcomings in the ethical dimensions of patient care, and research supports their view. In this issue of Annals, Erde suggests that physicians' incomes should depend on patients' assessments of their ethical behavior in much the same way that waiters' incomes depend on patrons' tips. Although Erde's solution is satiric, the problem is a serious one. The experiences and perspectives of patients regarding their own illness are undervalued by physicians. A truly patient-centered care demands that physicians elicit, understand, and respond to patients' perspectives. Tying physicians' pay to measurements of patient satisfaction is unlikely to dramatically improve the ethical quality of patient care as long as attention to the patient's perspective is seen as peripheral to "good medical care." Rather than relying on a single, easy "fix," we must re-examine all of professional development and practice. We need to choose persons for medical careers who will find patient-centered care rewarding; we need to provide such persons with training and socialization that underscores the value of personalized medicine; and we need to build institutions and systems that facilitate and reinforce patient-centered practice. The best ways to achieve these objectives are as yet unclear, but if we, as physicians, are offended by Erde's "modest proposal," then we must respond by proposing and implementing our own ideas about how patient care can become more humane. PMID- 2240884 TI - Severe acetaminophen toxicity in a patient receiving isoniazid. PMID- 2240885 TI - Annual pelvic examination. PMID- 2240886 TI - Diarrhea and AIDS. PMID- 2240887 TI - Functional asplenia after bone marrow transplantation. PMID- 2240888 TI - Gluten-free diet for AIDS-associated enteropathy. PMID- 2240889 TI - Diagnosis of Cushing disease. PMID- 2240890 TI - Nutritional deficiency and AIDS. PMID- 2240891 TI - Precautions against hepatitis B. PMID- 2240892 TI - Financial incentives. PMID- 2240893 TI - Parenting during residency. PMID- 2240894 TI - Authorship. PMID- 2240895 TI - Decision analysis in the evaluation of revascularization. PMID- 2240896 TI - Advocacy for methadone treatment. PMID- 2240897 TI - Emergence of recreational drug abuse as a major risk factor for stroke in young adults. AB - OBJECTIVE: To investigate the clinical and epidemiologic relations between recreational drug abuse and stroke in young persons. DESIGN: A case-control study based on medical records. SETTING: San Francisco General Hospital, a 400-bed municipal hospital. PATIENTS: Consecutive sample of 214 patients aged 15 to 44 years, admitted between 1979 and 1988 with a diagnosis of ischemic or hemorrhagic stroke. An equal number of control patients admitted with diagnoses of status asthmaticus, acute appendicitis, or acute cholecystitis were matched to stroke patients by age, sex, and year of hospitalization. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients with stroke (34%) were drug abusers compared with 18 (8%) of the controls. In 47 patients with stroke, temporal proximity of drug administration (n = 34) or infectious endocarditis (n = 13) suggested a direct association between drug abuse and stroke. After controlling for other identifiable stroke risk factors, the estimated relative risk for stroke among drug abusers compared with that among non-drug abusers was 6.5 (95% CI, 3.1 to 13.6), and this increased to 49.4 (CI, 6.4 to 379.0) for those patients whose symptoms began within 6 hours of drug administration. Among patients less than 35 years of age, drug abuse was the most commonly identified potential predisposing condition (47%), and it was the only condition with a significantly elevated relative risk for stroke (11.7; CI, 3.2 to 42.5). Further, a substantial rise in the proportion of drug-related strokes was observed in the last 3 years of the study (31% in 1986 to 1988, compared with 15% in 1979 to 1985, P = 0.008). Cocaine, especially recently, was the drug used most frequently in drug-related strokes. CONCLUSION: In an urban population such as ours, recreational drug abuse appears to be a prominent and growing risk factor for strokes in young adults. PMID- 2240898 TI - Sexual and physical abuse in women with functional or organic gastrointestinal disorders. AB - STUDY OBJECTIVES: To determine the prevalence of a history of sexual and physical abuse in women seen in a referral-based gastroenterology practice, to determine whether patients with functional gastrointestinal disorders report greater frequencies of abuse than do patients with organic gastrointestinal diseases, and to determine whether a history of abuse is associated with more symptom reporting and health care utilization. DESIGN: A consecutive sample of women seen in a university-based gastroenterology practice over a 2-month period was asked to complete a brief questionnaire. MEASUREMENTS: The self-administered questionnaire requested information about demographics, symptoms, health care utilization, and history of abuse. Physicians indicated the primary diagnosis for each patient and whether she had ever discussed having been sexually or physically abused. RESULTS: Of 206 patients, 89 (44%) reported a history of sexual or physical abuse in childhood or later in life; all but 1 of the physically abused patients had been sexually abused. Almost one third of the abused patients had never discussed their experiences with anyone; only 17% had informed their doctors. Patients with functional disorders were more likely than those with organic disease diagnoses to report a history of forced intercourse (odds ratio, 2.08; 95% CI, 1.03 to 4.21) and frequent physical abuse (odds ratio, 11.39; CI, 2.22 to 58.48), chronic or recurrent abdominal pain (odds ratio, 2.06; CI, 1.03 to 4.12), and more lifetime surgeries (2.7 compared with 2.0 surgeries; P less than 0.03). Abused patients were more likely than nonabused patients to report pelvic pain (odds ratio, 4.05; CI, 1.41 to 11.69), multiple somatic symptoms (7.1 compared with 5.8 symptoms; P less than 0.001), and more lifetime surgeries (2.8 compared with 2.0 surgeries; P less than 0.01). CONCLUSIONS: We found that a history of sexual and physical abuse is a frequent, yet hidden, experience in women seen in referral based gastroenterology practice and is particularly common in those with functional gastrointestinal disorders. A history of abuse, regardless of diagnosis, is associated with greater risk for symptom reporting and lifetime surgeries. PMID- 2240899 TI - Serum and tissue magnesium concentrations in patients with heart failure and serious ventricular arrhythmias. AB - OBJECTIVE: To compare magnesium concentrations in serum and tissue from patients with heart failure. Two groups of patients were compared, those with or without serious ventricular arrhythmias. DESIGN: Consecutive enrollment. Blinded laboratory analyses. SETTING: Referral inpatient service of the cardiology division of a university hospital. PATIENTS: Twenty-three patients with idiopathic dilated cardiomyopathy and mild to moderately severe congestive heart failure (New York Heart Association functional class II to IV) were divided into two groups: 9 patients with sustained ventricular tachycardias and 14 patients without serious ventricular arrhythmias (control). INTERVENTIONS: Medications for heart failure were withdrawn 12 hours or more before study. Antiarrhythmic therapy was continued throughout the study. MEASUREMENTS AND MAIN RESULTS: The patients had skeletal muscle biopsies, myocardial biopsies, and blood sampling for the analysis of magnesium concentrations. No statistically significant differences in the mean magnesium concentrations in serum, circulating mononuclear cells, skeletal muscle, and myocardium were found when the 9 patients with ventricular arrhythmias were compared with the 14 control patients without serious ventricular arrhythmias. CONCLUSIONS: In a general, ambulatory sample of patients with heart failure, magnesium depletion in serum and tissue does not appear to occur more commonly in patients with serious ventricular arrhythmias than in patients without serious ventricular arrhythmias. PMID- 2240900 TI - Gallium nitrate for advanced Paget disease of bone: effectiveness and dose response analysis. AB - OBJECTIVE: To evaluate whether a brief course of treatment with gallium nitrate can reduce biochemical parameters of accelerated bone turnover in patients with advanced Paget disease. DESIGN: Unblinded trial, decreasing dose schedules of gallium nitrate. SETTING: University hospital with primary orthopedic and metabolic bone disease specialty. PATIENTS: Ten patients with advanced Paget disease who had previously received conventional therapy consisting of calcitonin, etidronate, or mithramycin. INTERVENTIONS: Five patients were entered into each of three dose schedules: 2.5 mg/kg body weight per day by continuous intravenous infusion for 7 days; 0.5 mg/kg per day for 14 days by subcutaneous injection; and 0.25 mg/kg per day for 14 days by subcutaneous injection. Several patients were treated with different dose schedules. Patients were followed until relapse. RESULTS: Fifteen courses of treatment were administered to ten patients. Reductions in serum alkaline phosphatase and urinary hydroxyproline excretion were observed after treatment with each dose schedule. After treatment with high, intermediate, and low doses, the median maximum decreases in serum alkaline phosphatase activity were 49%, 39%, and 18%, respectively. The median maximum decreases in urinary hydroxyproline excretion were 50%, 52%, and 16%, respectively. The maximum decrease in urinary hydroxyproline excretion occurred within a median of 2 weeks from the start of treatment, whereas the maximum decrease in serum alkaline phosphatase activity occurred substantially later at a median of 6 weeks. All treatment schedules were well tolerated. Response duration was highly variable (range, 6 to 42 weeks). CONCLUSIONS: Short-term treatment with gallium nitrate can reduce biochemical parameters of disease activity in patients with advanced Paget disease of bone. Larger trials using low-dose intermittent treatment schedules are required to evaluate the safety and effectiveness of this therapy. PMID- 2240901 TI - Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment. AB - PURPOSE: To evaluate evidence that concurrent infection with human immunodeficiency virus (HIV) alters both the natural history of syphilis (by increasing the frequency of early neurosyphilis) and the response to penicillin. DATA IDENTIFICATION: Review of major works on syphilis in the English language and files maintained since 1971, supplemented by a systematic search using Index Medicus and MEDLARS. DATA EXTRACTION: The works mentioned above were critically reviewed for information on early neurosyphilis and, where relevant, HIV infection. RESULTS OF DATA ANALYSIS: The central nervous system is regularly involved in early syphilis. Standard recommended doses of benzathine penicillin provide cerebrospinal fluid levels that are probably at the borderline of efficacy, and cure relies on treatment and an adequate host immune response. Early neurosyphilis, appearing within 2 years of onset of infection with Treponema pallidum, was uncommon in the prepenicillin era and usually occurred after inadequate therapy. This complication was exceedingly rare in the first three decades of penicillin use. In contrast, in the past decade, 40 patients with HIV infection have been reported to have asymptomatic neurosyphilis, or syphilitic meningitis, cranial nerve abnormalities (predominantly in cranial nerves II and VIII), or cerebrovascular accidents, singly or together. In 40% of cases, HIV infection was first diagnosed when neurologic symptoms appeared. Of the 38 patients for whom information was available, 18 had the acquired immunodeficiency syndrome (AIDS), 7 had AIDS-related complex, and 13 had antibody to HIV. Sixteen had previously been treated for syphilis, of whom 5 (31%) had received benzathine penicillin within the previous 6 months. Preliminary data also suggest that skin lesions and VDRL (Venereal Disease Research Laboratory) antibody in HIV-infected patients with secondary syphilis respond more slowly to conventional penicillin therapy. CONCLUSION: Intensive therapy and follow-up observation is indicated for early syphilis in HIV-infected subjects. Novel approaches to treatment deserve systematic evaluation. PMID- 2240904 TI - Living the patient's story. PMID- 2240902 TI - Cooperation between health professionals from the United States and the Union of Soviet Socialist Republics. Conclusions from a trip to the Soviet Union. AB - The United States has long made its academic medical resources available to foreign medical graduates. Conspicuously absent from the number of foreign nationals, however, have been physicians, scientists, and educators from the Soviet Union. Under the new conditions of perestroika, Soviet medical professionals are seeking ways in which to open up broad collaboration with their American counterparts. Agreements are being sought between national organizations, between academic medical institutions, and for the exchange of individual scholars. Cooperation in the area of medical education is one of the distinctive bridges on the path to mutual understanding that will represent a strong link in the public diplomacy of the two superpowers. We recently had the opportunity to discuss in Moscow some of the issues with the U.S.S.R. Minister of Health and with the Pro-rector for International Programs of the Central Institute for Advanced Medical Studies, as well as with faculty members, young medical scientists, and medical students of the Moscow Medical Institutes. We describe briefly many of the similarities and some of the dissonances between our two health systems and set forth ideas for an exchange program in medical education. PMID- 2240903 TI - Improving outcomes of analgesic treatment: is education enough? AB - Frequent undertreatment of analgesic-responsive acute pain and chronic cancer pain persists, despite intensive efforts to provide clinicians with information about analgesics. A set of background factors must be addressed in interventions to improve pain treatment: Traditional patterns of clinician and patient interaction on the ward, quality assurance, and drug regulatory practices do not support prompt recognition and treatment of pain. Possible interventions to modify these patterns of daily practice include monitoring and displaying patient pain ratings routinely, making available educational tools to assist optimal drug ordering, encouraging patients to communicate about unrelieved pain, reviewing quality assurance of pain treatment regimens, increasing behavioral research into analgesic prescribing, and selectively modifying narcotics regulatory practices. PMID- 2240905 TI - A steroid-responsive nephrotic syndrome in a patient with human immunodeficiency virus (HIV) infection. PMID- 2240906 TI - Corticosteroid-associated blue toe syndrome: role of antiphospholipid antibodies. PMID- 2240907 TI - Intravenous immunoglobulins in gram-negative bacteremia. PMID- 2240908 TI - Molecular genetics of chronic myelogenous leukemia. PMID- 2240909 TI - Fluconazole-induced thrombocytopenia. PMID- 2240912 TI - Physicians and the pharmaceutical industry. PMID- 2240910 TI - Screening for colorectal cancer. PMID- 2240911 TI - Cigarette smoking, not carbon monoxide, is the problem. PMID- 2240913 TI - Predicting type II diabetes in persons at risk. PMID- 2240914 TI - Expanding the use of thrombolytic therapy for acute myocardial infarction. PMID- 2240916 TI - High blood cholesterol in elderly men and the excess risk for coronary heart disease. AB - OBJECTIVE: To determine whether high blood cholesterol is an important risk factor for mortality from coronary heart disease in elderly men. DESIGN: Cohort study with a mean follow-up of 10.1 years. SETTING: A health maintenance organization. PATIENTS: The cohort included 2746 white men 60 to 79 years of age who had no self-reported history of coronary heart disease. MEASUREMENT AND MAIN RESULTS: A total of 260 deaths occurred during 27,842 person-years of follow-up. The relative risk for mortality from coronary heart disease in men 60 to 79 years of age in the highest serum cholesterol quartile was 1.5 (95% CI, 1.2 to 2.0) compared with those in the three lower quartiles combined. The relative risk did not change greatly with age, ranging from 1.4 in men 60 to 64 years of age to 1.7 in men 75 to 79 years of age. However, because mortality from coronary heart disease increased with age, the excess risk for such mortality attributable to elevated serum cholesterol levels increased fivefold over these 20 years, from 2.2 deaths per 1000 person-years to 11.3 deaths per 1000 person-years. CONCLUSIONS: Our results support those of other observational studies in elderly men. If treatment of high blood cholesterol is as effective in reducing cholesterol-related risk for coronary heart disease after 65 years of age as it is in middle-aged men, it might actually produce greater reductions in mortality due to coronary heart disease. A clinical trial is needed to confirm this extrapolation. PMID- 2240915 TI - Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. AB - OBJECTIVE: To determine whether insulin resistance or insulin deficiency is primary in the pathogenesis of type II diabetes. DESIGN: Cohort analytic study of persons with normal glucose tolerance but with a high risk for developing type II diabetes (average follow-up time, 13 years). SETTING: Outpatients had an intravenous glucose tolerance test and were contacted periodically to ascertain diagnoses of diabetes. PARTICIPANTS: One hundred and fifty-five normal offspring, ranging in age from 16 to 60 years, of two parents with type II diabetes and 186 normal control subjects in the same age range who had no family history of diabetes. MEASUREMENTS AND MAIN RESULTS: Two phenotypic characteristics distinguished the offspring of diabetic parents from control subjects. They had slower glucose removal rates (Kg) (P less than 0.01) and higher insulin levels (fasting and during the second phase of insulin response to intravenous glucose; P less than 0.0001) than did control subjects, even after adjustment for differences in obesity. Sixteen percent of the offspring developed type II diabetes. Mean Kg at baseline was 1.7%/min among offspring who subsequently developed diabetes, 2.2%/min among offspring who remained nondiabetic, and 2.3%/min among control subjects. Corresponding means for first-phase insulin were 498, 354, and 373 pM, respectively, whereas second-phase insulin means were 329, 117, and 87 pM, respectively. In multivariate analysis, low Kg and high serum insulin levels independently increased the risk for developing diabetes among the offspring of diabetic parents. CONCLUSIONS: One to two decades before type II diabetes is diagnosed, reduced glucose clearance is already present. This reduced clearance is accompanied by compensatory hyperinsulinemia, not hypoinsulinemia, suggesting that the primary defect is in peripheral tissue response to insulin and glucose, not in the pancreatic beta cell. PMID- 2240917 TI - Cardiovascular effects of the somatostatin analog octreotide in acromegaly. AB - OBJECTIVE: To determine the cardiovascular effects of the somatostatin analog octreotide in patients with acromegaly. DESIGN: Prospective nonrandomized study. SETTING: Referral-based endocrinology clinic. PATIENTS: Seven patients with active acromegaly, three of whom had refractory congestive heart failure. The other four patients were free of symptoms associated with heart failure. INTERVENTIONS: All patients were treated with octreotide, 100 to 500 micrograms subcutaneously three times daily. The three patients with heart failure continued to receive cardiovascular therapy (angiotensin converting enzyme inhibitors, digitalis, diuretics). MEASUREMENTS AND MAIN RESULTS: During octreotide therapy, patients showed a rapid decrease in growth hormone and insulin-like growth factor 1 (IGF-1): Mean levels (+/- SD) fell from 28.1 +/- 32.7 micrograms/L to 5.2 +/- 8.3 micrograms/L and 740 +/- 126 micrograms/L to 372 +/- 64 micrograms/L, respectively (P less than 0.025). Plasma volume returned to normal and heart rate decreased significantly. In the four patients without heart failure, right-heart catheterization done before and after 3 months of octreotide therapy showed an 18.3% +/- 11% reduction in stroke volume and a return to normal of the cardiac index. The three patients with congestive heart failure, evaluated before and after 40 days and up to 2 years of therapy, showed a dramatic clinical improvement that was associated with an increase in stroke volume (by 24% to 51%). In these patients, the cardiac index remained in the normal range, filling pressures were markedly decreased, and pulmonary wedge pressure returned to normal. This improvement was sustained for up to 3 years in the two patients with heart failure who were receiving long-term treatment. CONCLUSION: The rapid and sustained cardiac improvement seen in our patients shows that octreotide therapy for patients with acromegaly may be highly beneficial, even in those patients with advanced cardiac failure. PMID- 2240918 TI - Clarifying confusion: the confusion assessment method. A new method for detection of delirium. AB - OBJECTIVE: To develop and validate a new standardized confusion assessment method (CAM) that enables nonpsychiatric clinicians to detect delirium quickly in high risk settings. DESIGN: Prospective validation study. SETTING: Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University (site 1) and in general medicine wards at the University of Chicago (site 2). PATIENTS: The study included 56 subjects, ranging in age from 65 to 98 years. At site 1, 10 patients with and 20 without delirium participated; at site 2, 16 patients with and 10 without delirium participated. MEASUREMENTS AND MAIN RESULTS: An expert panel developed the CAM through a consensus building process. The CAM instrument, which can be completed in less than 5 minutes, consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R). An a priori hypothesis was established for the diagnostic value of four criteria: acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion. At both sites, the diagnoses made by the CAM were concurrently validated against the diagnoses made by psychiatrists. At sites 1 and 2 values for sensitivity were 100% and 94%, respectively; values for specificity were 95% and 90%; values for positive predictive accuracy were 91% and 94%; and values for negative predictive accuracy were 100% and 90%. The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium. The CAM was shown to have convergent agreement with four other mental status tests, including the Mini-Mental State Examination. The interobserver reliability of the CAM was high (kappa = 0.81 - 1.0). CONCLUSIONS: The CAM is sensitive, specific, reliable, and easy to use for identification of delirium. PMID- 2240919 TI - Selection of patients with acute myocardial infarction for thrombolytic therapy. AB - PURPOSE: To critically review the current recommendations regarding the eligibility of patients with myocardial infarction for thrombolytic therapy. DATA IDENTIFICATION: Relevant studies published from January 1980 to January 1990 were identified through a computerized search of the English-language literature using MEDLINE and by a manual search of the bibliographies of all identified articles. STUDY SELECTION: All randomized, controlled trials of intravenous thrombolysis in acute myocardial infarction and unstable angina were reviewed. Smaller, observational studies and previous review articles were included when relevant to the discussion. DATA EXTRACTION: Key data were extracted from each article, including the proportions of patients eligible for thrombolysis, the reasons for exclusion from thrombolytic therapy, and the clinical outcomes of patients treated and of those excluded from treatment. The validity of certain exclusion criteria was examined using subgroup analysis from the large, randomized mortality trials of intravenous thrombolysis and observations from smaller, nonrandomized studies. RESULTS OF DATA SYNTHESIS: To date, relatively few patients with myocardial infarction have been considered eligible for fibrinolytic therapy. In this group, both early and late mortality have been significantly reduced. Patients excluded from thrombolysis, however, continue to have a high early mortality. The data suggest that the potential benefits of this treatment might be extended to selected high-risk subgroups. In particular, the risk-benefit ratio may favor the inclusion of otherwise healthy elderly patients; certain patients presenting more than 6 hours after the onset of symptoms; and patients with a history of controlled systolic hypertension or brief, nontraumatic cardiopulmonary resuscitation. The data do not support the use of fibrinolytic therapy as primary treatment in patients with unstable angina or suspected myocardial infarction in the absence of confirmatory electrocardiographic changes. CONCLUSIONS: The full potential of thrombolytic therapy to alter the natural history of acute myocardial infarction can only be realized through the continued evaluation of selection criteria and the identification and treatment of the greatest possible number of eligible patients. PMID- 2240920 TI - Preoperative screening: value of previous tests. AB - OBJECTIVE: To determine the frequency of tests done in the year before elective surgery that might substitute for preoperative screening tests and to determine the frequency of test results that change from a normal value to a value likely to alter perioperative management. DESIGN: Retrospective cohort analysis of computerized laboratory data (complete blood count, sodium, potassium, and creatinine levels, prothrombin time, and partial thromboplastin time). SETTING: Urban tertiary care Veterans Affairs Hospital. PATIENTS: Consecutive sample of 1109 patients who had elective surgery in 1988. MEASUREMENTS AND MAIN RESULTS: At admission, 7549 preoperative tests were done, 47% of which duplicated tests performed in the previous year. Of 3096 previous results that were normal as defined by hospital reference range and done closest to the time of but before admission (median interval, 2 months), 13 (0.4%; 95% CI, 0.2% to 0.7%), repeat values were outside a range considered acceptable for surgery. Most of the abnormalities were predictable from the patient's history, and most were not noted in the medical record. Of 461 previous tests that were abnormal, 78 (17%; CI, 13% to 20%) repeat values at admission were outside a range considered acceptable for surgery (P less than 0.001, frequency of clinically important abnormalities of patients with normal previous results with those with abnormal previous results). CONCLUSIONS: Physicians evaluating patients preoperatively could safely substitute the previous test results analyzed in this study for preoperative screening tests if the previous tests are normal and no obvious indication for retesting is present. PMID- 2240921 TI - Physician shortage in occupational and environmental medicine. AB - OBJECTIVE: To determine future training needs for physicians in occupational and environmental medicine based on goals established by the Institute of Medicine (IOM) for clinical practice in the field. DESIGN: A critical review of previously published estimates of the need and supply of physicians with clinical training in occupational and environmental medicine with the application of currently available data to produce revised estimates. MEASUREMENTS AND MAIN RESULTS: Need estimates reviewed from the National Institute for Occupational Safety and Health, the Graduate Medical Education National Advisory Committee (GMENAC), and the Bureau of Health Professions. Supply figures reviewed from GMENAC, the American Medical Association, the American College of Occupational Medicine, and the American Board of Preventive Medicine. Revised need figures are based on the estimated number of occupational and environmental physicians needed to provide adequate nationwide coverage as full-time academic faculty, community-based specialists, and public health physicians in state and local agencies. Revised supply estimates are based on review of available data. Need is estimated at 4600 to 6700 physicians (board-certified or eligible or with special competence in occupational and environmental medicine). Supply is estimated at 1200 to 1500. CONCLUSIONS: This review identified a deficit of 3100 to 5500 physicians in this newly evolving specialty. In order to address this shortfall in the next decade, graduate specialty training would need to be increased to about 3 to 5 times the current maximum capacity. PMID- 2240922 TI - Effects of different calcium antagonists on proteinuria associated with diabetes mellitus. PMID- 2240923 TI - Fluid loading in septic shock. PMID- 2240924 TI - Treatment of cryptococcal meningitis in AIDS. PMID- 2240925 TI - Chronic airflow limitation and obesity. PMID- 2240926 TI - Syncope and functional infranodal block. PMID- 2240927 TI - "Jump starting" the immune system. PMID- 2240928 TI - Physician supply and the health care crisis. PMID- 2240929 TI - Unwanted journals and the environment. PMID- 2240930 TI - [Peptic ulcer and Helicobacter pylori]. PMID- 2240932 TI - [Intestinal hormones and peptic ulcer]. PMID- 2240931 TI - [Billroth I using mechanical staplers in peptic ulcer (experience in 112 operated cases)]. PMID- 2240933 TI - [Tumors of the carotid glomus (chemodectomas)]. AB - Two cases of carotid body tumor (chemodectomas) have been reported and at this regard the international literature reviewed. Concerning the diagnosis selective angiograms represent the investigation of choice in clinical assessment and planning operative approach. Doppler-ultrasound results particularly useful in the follow up of patients after surgery. With advances in vascular technique, complete excision of the tumor has become possible and is now associated with minimal morbidity and mortality. Survival rate of resected patients is equivalent to that for sex age matched control subjects. PMID- 2240934 TI - [Surgery of pulmonary and hepatic metastases]. AB - In recent years surgery for hepatic and pulmonary metastases has been undertaken with a curative intent in a growing percentage of cases. In the present study the Authors evaluate their own experience in such a field, and summarize the state of the art, as it appears from a review of the international literature. At present, the subject is not settled, as several aspects are matter of debate (prognostic significance of free interval, tumor doubling time, number and location of metastatic lesions, histologic type, and stage, of the primary tumor, approach to synchronous metastases, accuracy of preoperative diagnosis), with different therapeutic implications according to the hepatic or pulmonary site. Pulmonary metastases should be managed by resection through a median sternotomy, in order to allow thorough exploration of both lungs. Hepatic lesions (from colorectal primaries) should be resected with a free margin not less than 1-2 cm. The need for uniformity of selection criteria and for the establishment of protocols including adjuvant therapy is strongly felt. PMID- 2240935 TI - [State of the art in the treatment of peptic ulcer]. PMID- 2240936 TI - [Treatment of pancreatic pseudocysts: personal experience]. AB - The authors reported their experience of 13 patients with pancreatic pseudocyst observed within the period 1982-1987. Three patients underwent external drainage, 9 internal drainage and 1 exeretic operation. On the base of the results the authors conclude that the internal drainage should be considered the choice operation of pancreatic pseudocysts because of the lower mortality and morbidity. PMID- 2240937 TI - [Antibiotic prophylaxis in the control of infections in surgery: comparison of treatment in different types of surgery]. AB - Despite the development of the most recent and powerful antimicrobic agents, surgical infections are to this day a constant threat to surgeons, rendering negative otherwise successful surgical results. It seems therefore essential that during surgical operations--which according to Altemeier's classification are defined as "contaminated" and "potentially contaminated"--patients undergo a perioperative antibiotic prophylaxis in order to assure elevated tissue levels of antibiotic as necessary. A perspective trial of two standard protocols of short term prophylaxis versus cefoperazone has been here outlined, given that in a recent study cefoperazone showed a positive effect in destroying the intestinal flora of patients even though this was carried out in experimental and not in clinical conditions. 177 patients were selected for this study with a breakdown of 26 and 42, that is twenty-six underwent potentially contaminated procedures and 42 contaminated procedures. Selecting at random, fifty percent of the first group was treated with cefoxitin, and the other half with cefoperazone; as far as the second group is concerned half the sample of patients was treated with cefoperazone and then compared with the other half who had been given an association of piperacillin and metronidazole. Primary septic complications amounted to 7.3% (13 cases); 7.6% in the first group (2 cases) and 21% in the second (9 cases). The different of sepsis between the two groups was not statistically significant although cefoperazone showed a higher septic result in contaminated surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240939 TI - [Neuroendocrine surgery in Parkinson's disease: comparative analytical evaluation of approaches to microsurgical adrenalectomy. Experimental studies]. AB - In this experimental contribution to the study of neurobiological interactions between adrenal medullary graft and CNS, is presented a model to estimate the approaches to rat adrenalectomy using statistical inference techniques. Eighteen rats were divided into three samples. The members of every sample were left adrenalectomized using lombotomic, anterior transperitoneal and posterior approaches respectively. A score was attributed to every experimentally meaningful parameter, according a previously well established plan. Scores were tested by analysis of variance and by previously planned orthogonal comparisons. Mean, standard deviation of every sample score and confidence interval for mean difference were computed. Statistical analysis results show that, objectively, there is a meaningful difference between anterior approach and posterior or lateral approach, anterior approach being more difficult then posterior or lateral approach, while there is not meaningful difference between posterior and lateral approach. Subjectively, on the contrary, there are not meaningful differences between three approaches to left adrenalectomy statistically. PMID- 2240938 TI - [Clinical considerations of jejunal carcinoma]. AB - The carcinoma of the jejunum represents 3-6.5% of gastric intestinal tumors and 33-50% of small intestine carcinomas. The observation of a case of jejunum carcinoma has offered the authors the idea for a critical revision on the subject. After an examination on the diagnostic, anatomopathological, clinical and therapeutic problems, the authors underline the importance of the precocious diagnosis of neoplasia; in fact the jejunum carcinoma is characterized by a hidden and aspecific symptomatology and by dangerous evolution; besides the site is difficult for an organic study with the common methods of investigation. Therefore, in all patients in whom the suspicion of a jejunum pathology exists, it is indispensable to carry out a precise diagnostic iter which is based on radiological endoscopic and tomographic investigation: in fact the small intestine and the jejunum in particular are intestinal tracts that are explored with difficult and therefore at times only an accurate effecting of the radiological study can permit a precocious diagnosis the only valid supposition for the carrying out of a truly radical surgical therapy and for the acquiring of a batter prognosis. PMID- 2240940 TI - [Colostomy control using an original occluding device. A clinico-experimental study]. AB - After having examined different methods as to continence colostomy, the authors introduce their own control system for the stoma. The study was carried out on 6 colostomized patients. Preliminary, the intraluminal pressure in closed colostomy was recorded. Pressure waves, largely varying from patient to patient, were obtained as to frequency of waves and pressure values. The same variations were observed during meals waking and sleeping. Sometimes the patients suffered from serious disorder, but in most cases they did not feel pain. A catheter, provided with an inflatable balloon for closing the stoma, formed the system tested. It was also provided with a second intraluminal low-pressure inflated balloon, connected with an external compensating chamber. As a result of the system the pressure dropped down to about 1/6 compared with the reference values observed under the same conditions. In addition, the continence was complete and the patient did not suffer from any disorder in non-stop recordings up to 24 hours. We believe that the system may be useful for colostomized patients if carefully carried out. PMID- 2240941 TI - [Role of fiber optics endoscopy in the diagnosis and follow up of peptic ulcer]. PMID- 2240942 TI - [Is it possible to prevent cognitive disorders in the elderly?]. PMID- 2240943 TI - [Inflammation proteins in Horton's disease. Prospective study of 25 patients]. AB - In a study of 25 giant cell arteritis patients, whose diagnoses were made by temporal artery biopsy, the authors compared the evolution of the erythrocyte sedimentation rate (ESR) with those of the acute phase proteins (APP): fibrinogen (F), C reactive protein (CRP), orosomucoid (O), haptoglobin (H) and alpha 2 globulins (alpha 2-G), before, during and after corticotherapy; 165 laboratory analyses were made. Prior to treatment, ESR was increased in 96% of the patients, O and H in 100%, F and CRP in 96% and alpha 2-G in 92%. CRP showed the greatest mean increase (21x). Statistically significant positive correlations were found between ESR and alpha 2-G, F, CRP and O. No significant relationship was observed between APP and the occurrence of ophthalmological complications or the length of treatment. The CRP level returned to normal within the first week of steroid therapy for 76% of the patients, before ESR, F and O. During the withdrawal phase of corticotherapy, an ESR greater than 30 mm almost always corresponded to an inflammatory syndrome and an ESR of less than 15 mm to its absence (kappa coefficient = 0.64, p less than 0.001); however, an ESR between 15 and 30 mm did not enable us to draw a conclusion as to the absence or presence of such a syndrome. After terminating steroid therapy, the relationship between ESR and an inflammatory syndrome was weaker (kappa coefficient = 0.57, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2240945 TI - [Hyperparathyroidism with severe hypercalcemia. Treatment and results]. AB - From 1960 to 1988, we successfully treated 1,200 primary hyperparathyroid patients. The serum calcium level was higher than 3.75 mmol/l (150 mg/l) in 75 patients. Sixty-five patients had acute primary hyperparathyroidism and 10 had asymptomatic severe hypercalcemia. Before admission to our department, most of the patients were given medication to lower their serum calcium levels. Analysis of our diagnostic and therapeutic experience leads us to insist upon the importance of prompt medical treatment and rapid surgical intervention. Only surgery can adequately treat severe hyperparathyroidism. PMID- 2240944 TI - [Restenosis after transluminal coronary angioplasty. Clinical and therapeutic aspects]. AB - To assess the incidence and clinical presentation of restenosis after successful coronary angioplasty, and the short- and mid-term results of its treatment, 160 patients, who underwent a first coronary angioplasty between May 1987 and December 1988, were closely monitored. Restenosis is defined as a loss of 50% or more of the initial gain in area and/or 30% or more in diameter, or chronic coronary occlusion. These criteria were met in 43 patients (27%) within 5.1 months (1-6 months), on the average, after angioplasty. Restenosis was expressed as unstable angina in 51% of the patients, stable angina in 30%, and abnormal thallium myocardial scintigraphy under exercise in 14%. Myocardial infarction was never the revealing symptom. In 63% of the cases, the pain caused by restenosis repeated the initial angina. A second angioplasty was performed in 75% of the patients with a success rate of 93%, in the absence of an occlusion, and a 37% rate of further restenosis. PMID- 2240947 TI - [Diabetic maculopathy]. PMID- 2240946 TI - [Pulmonary artery hypertension in systemic lupus erythematosus]. PMID- 2240948 TI - [New prospects of immunotherapy in rheumatoid polyarthritis]. PMID- 2240949 TI - [Impotence: therapeutic possibilities]. PMID- 2240950 TI - [First Consensus Conference on anti-infectious Treatment. Pneumocystosis in HIV infection. Brief report (11-13 May 1990)]. PMID- 2240951 TI - [Pulmonary artery hypertension and systemic lupus erythematosus. A case with hemodynamic study]. PMID- 2240952 TI - [Association of paroxysmal nocturnal hemoglobinuria and polymyositis]. PMID- 2240953 TI - [Familial amyloidosis of AL type and factor X deficiency. The valve of long-term colchicine administration]. PMID- 2240954 TI - [Still's disease in adults with a pulmonary site]. PMID- 2240955 TI - [Eosinophilic meningitis. Observations on a case contracted in New Caledonia]. PMID- 2240956 TI - [Planning in mental health--is it possible?]. AB - The author opens the subject by questioning "why" and "how" to plan for mental health. Planification is a public health process. This process made modern countries able to develop health care policies in accordance to scientific progress. This allowed to stop the transmission of communicable diseases. Mental health disorders are one of the 4 public health priorities along with cardio vascular diseases, cancers an consequences of accidents. New care methods have to be found in order to be adapted to recent needs. In many countries, mental health care have been and still are on the way to be modified. These major modifications will be illustrated by the French "sectorisation" which will be replaced in the context of complete reconversion of the French mental health care system. Two research streams will be proposed: research focused on the health care system which will enlight the different systems, their characteristics, activities and adequation; epidemiological studies in order to measure population needs in term of mental health, to clarify how mental health disorders appear and what sort of care are used by the persons. To illustrate these themas, the author will present his own experience. For more than 25 years he was operating on complex private mental health care system using the resources of an epidemiological unit in order to plan the development of this care system. PMID- 2240957 TI - [Continuity and breaks in psychiatry. Introduction]. PMID- 2240958 TI - [Continuity and discontinuity: definitions]. PMID- 2240959 TI - [Lithium as founding the concept of endogenous mental disease]. AB - The abnormal life--potentially the death--of the cell can be restored by a metalloid--lithium--which is nearly as common as sodium in the mineral world. This established fact grounds indirectly, contrary to apparent and scientific logic, the concept of endogenous brain disease which was until then an abstract concept because of a lack of objective evidence. Seven case reports are described. PMID- 2240960 TI - [Paradoxes in adolescence: break and continuity]. AB - The psychopathological studies on adolescence underline the paradoxical behaviours during this period of life. After the analysis of its concept we show in which way the paradox helps to maintain the continuity of psychological life during the crisis. Thus impossible choices which are part of the contradiction in adolescents be avoided. It will be necessary to provoke the emergence of the paradox from the contradictions linked with hospitalization through on hospitalization to make the most of the letter in the therapeutic process. PMID- 2240961 TI - [The bird's name is the father's name]. PMID- 2240962 TI - [From order to chaos in psychiatry]. PMID- 2240963 TI - [Limitations of irrationality in our psychiatric practice]. PMID- 2240964 TI - [I leave for good: I shall not come back before tonight]. PMID- 2240965 TI - [From Pinel to Bateson: change in continuity]. PMID- 2240967 TI - [The unknown of knowledge in psychiatry]. PMID- 2240966 TI - [Continuity in break: the unbalanced patient's life]. PMID- 2240968 TI - [Psychoses in children and security units]. PMID- 2240969 TI - [Mythomania: conceptual changes or symptomatologic illusion?]. PMID- 2240970 TI - [Hospital, patient care team, continuity or discontinuity of care]. PMID- 2240971 TI - ["Where have our loves gone..."]. PMID- 2240972 TI - [Continuity and breaks of an indestructible bond in psychiatry]. PMID- 2240973 TI - [Short of and beyond words: breaks and continuity in language]. PMID- 2240974 TI - [Psychic injury]. PMID- 2240975 TI - [Concepts of the relationship between dementia and depression in Weingartner's works: a critical study]. AB - The School of Weingartner has construct a theoretical framework for defining cognition, in which changes in cognitive performance may be related to alterations in "intrinsic" cognitive processes (episodic memory, semantic memory, processes requiring effort or performed more automatically) or non cognitive "extrinsic" processes (sensitivity to reinforcement, arousal/activation, sensorimotor capabilities, mood). The empiric fertility of this pattern enriches our knowledges about depression and dementia. It is able to describe suitably some relevant facts under the view of a systemization and to support the idea that the component processes of memory are psychobiologically distinct. One cannot nevertheless ignore the issue of the value of the cognitive categories produced. It is possible to judge the episodic memory by the semantic memory? The basis on which the latter is measured is more restrictive than the basis upon which it was originally defined; the quantitative experiments don't take into account the modalities of the realization of the meaning. The notion of effort is still an area of investigation more than an enrichment of answers. It must be closely related to the notion of anticipation and take care of the spatiotemporal presentations from which the thought organizes the stimuli and adapts itself to the content of cognition in the circumstances of the experiment. A place must be done especially in dementia in the limits of the paradigmatic power of that pattern and in the criterions of exclusion separating the demented/-non depressed from the demented/depressed subjects. PMID- 2240977 TI - [From "morbus democraticus" to passionate idealism. Different reactions of French alienists after the Commune of Paris]. AB - Literary and medical works published immediately after the fall of the Commune of Paris purport an analysis which deserves a critical reading: the study of the influence that alcoholism and the federate movement had on each other, easily naive and not without excess, stamped with obviously reactionary emotions, appears as historically and scientifically questionable as the proposals towards an interpretation of the event in terms of mental pathology. The search of cases of insanity among the rebels, the idea that their acts could only express some kind of phrenopathic disorder opens the debate on the very existence of some morbid types such as Falret's and Pottier's "reasoning, inexhaustible and proselyte lunatics", the "many characters with fanciful projects, including reformists of the human race, and various utopists" that Morel includes in his classification of hereditary insanity, Serieux's and Capgras "idealists concerned with justice" found amongst delusions related to altruistic claims, Dide's and Guiraud's "idealistic passions, social reformers, anarchists" appear to us as very outdated classifications, on the border of the psychiatric field. PMID- 2240976 TI - [Knowledge about previous psychiatric care: is it a guaranty for therapeutic investment or a curse in psychiatric emergencies]. AB - A sample of 755 psychiatric emergencies taken in charge in the emergency service of the St-Luc Hospital, Brussels, was divided into two groups: patients without psychiatric background (498) and patients having received previous psychiatric care (238). A background of psychiatric follow-up strongly influence the taking on and therapeutic decisions to be made by psychiatrists: its absence protects the patient and is seen as the guaranty of a good investment from the therapist while the existence of previous psychiatric treatment rather leads to hospital in lieu of crisis intervention, even when the crisis mechanisms are not significantly different in both samples. PMID- 2240979 TI - [Towards a holistic model of mental disorder. Its analogical links with the contemporary scientific theories]. PMID- 2240978 TI - [Mental representations and neuronal networks]. PMID- 2240980 TI - [Evaluation of the risk factors of suicide in patients treated for mental disorders. Review of the literature from 1978 to 1988]. AB - Research on suicide risk factors among psychiatric patients has developed considerably over the last 10 years. The methodological problems are numerous. Tentatives of global prediction have been unsuccessful in describing one complete and specific picture of the mentally ill suicide, whereas lawsuits against psychiatrists are frequent after patients' suicides. Through the analysis of 37 publications from 1978 to 1988 the authors review the main suicide risk factors identified among treated psychiatric patients. PMID- 2240981 TI - [Standardized symptomatologic inventory adapted to psychiatric emergency]. AB - Clinical psychiatry, particularly in the case of hospital emergency, begins with the patient's benevolent observation. It goes on with the verbal communication, subordinated itself to linguistic problems. There are now daily cross-cultural practising and education in France. This is the presentation of a standardized inventory and of its instructions for use, created in connection with a multicentric currently analysed survey. The inventory can be used without major difficulty by non clinicians and general practitioners. PMID- 2240982 TI - [The myth of the psychiatric ward and its realities]. PMID- 2240983 TI - [Endogenous depression and the Newcastle scale II. Study with 147 patients (2)]. PMID- 2240985 TI - The use of biofeedback in the treatment of disorders of childhood. AB - Biofeedback has demonstrated its effectiveness in the treatment of childhood disorders over the cynicism of many clinicians. Its appropriateness to the pediatric population is not a function of the age of the subject, but of whether the disorder is amenable to treatment. To reiterate, not all disturbances are the same. Incontinence in the child with spina bifida may be different from incontinence in the aged. Hyperactivity in children, while often defined globally, has many concomitants, some of which help to determine the efficacy of biofeedback treatment. The instructions given are specific and easily understood and can be comprehended even by some of the youngest children. Biofeedback deserves to be considered as the treatment of choice, in a wide range of disorders occurring in childhood. PMID- 2240984 TI - Obesity. A biobehavioral point of view. PMID- 2240986 TI - A personal perspective on the development of social psychology. PMID- 2240987 TI - Biofeedback for disorders of initiating and maintaining sleep. AB - Sleep disturbances are a frequent reason for pediatric consultation. When the disturbance persists in the form of delays in entering or maintaining sleep (DIMS), a vicious cycle develops. As part of the cycle, vigilance or arousal occurs, further inhibiting sleep occurrence. Persistent DIMS requires treatment to interrupt this self-perpetuating sequence. Interruption requires reduction in psychophysiological arousal and deconditioning of the events surrounding sleep. Electromyographic (EMG) and thermal biofeedback in conjunction with relaxation training were used with three children who maintained high levels of arousal resulting from stresses common to their developmental stages. Within seven sessions, all three patients showed attenuation of arousal and symptom abatement marked by uninterrupted sleep. PMID- 2240988 TI - Is carbon monoxide a workplace teratogen? A review and evaluation of the literature. AB - Sixty case reports of carbon monoxide exposures involving pregnant women are reviewed. The circumstances under which carbon monoxide exposures adversely affected pregnancy and the types of effects seen are summarized. Severe acute exposures to carbon monoxide caused foetal death or toxic effects, including anatomical malformations and functional alterations. Foetal outcome was related to two major indices of carbon monoxide exposure: maternal blood carboxyhaemoglobin levels and maternal toxicity. PMID- 2240989 TI - Towards causal inference in occupational cancer epidemiology--I. An example of the interpretive value of using local rates as the reference statistic. AB - A brief overview is made of the criteria currently applied for establishing causation in occupational cancer epidemiology, and further criteria or 'desiderata' are proposed. These supplement the present somewhat simplistic ones for 'sufficient evidence of carcinogenicity' advocated by the International Agency for Research against Cancer in their monograph series. A frequent cause of confounding, not always appreciated, is the limited choice of a reference population for the statistical analyses. The study population is often an industrial one with marked regional and urban biases, especially for some of the cancers under scrutiny: these biases can influence markedly the resultant Standardized Mortality Ratio (SMR) calculated, and thus lead to misleading conclusions. The British Rubber Manufacturers' Mortality Study, 1946-1980, provided an opportunity to extract the data set of one of the 13 factories involved. Both local and national death rates were applied as a reference, and the use of the former substantially reduced the high SMRs previously recorded for lung and stomach cancers. This emphasized the need for further analyses when making other internal comparisons in order to accommodate more of the 'desiderata' listed. Ultimately causation can be inferred only after weighing up all the evidence, and must be based on a 'balance of probabilities'. PMID- 2240990 TI - The likelihood of detecting a significant hearing threshold shift among noise exposed workers subjected to annual audiometric testing. AB - The ability of annual audiometric surveillance to detect significant deteriorations in hearing sensitivity is examined considering the time pattern of the growth of noise-induced hearing loss. The yearly rate of change in hearing level due to the effects of noise exposure and age is computed from a mathematical model put forward in the International Standard ISO 1999 (1989). The first-order derivative of hearing level associated with noise and age was compared with different criteria of significant threshold shift (STS). The results show that the potential annual variation in hearing level at 4 kHz, the audiometric frequency most affected by noise, is always less than the minimum margin of error of audiometry under exposure to 90 dBA-8 h. At 100 dBA it nearly equals the margin of error only for the very first year of exposure and for the most sensitive individuals. The rate of change in hearing threshold at 4 kHz is less than or equal to 1 dB per year for a major portion of a population exposed to an average noise level of 90 dBA-8 h (+/- 5 dB SD). For other audiometric frequencies, or for combinations of frequencies, this rate is even lower. It is also demonstrated that, using annual hearing tests, the likelihood of measuring an STS in a noise-exposed population is very small. It would be nearly equal to the likelihood of some workers being exposed to 100 dBA-8 h or more for a first year. Such results throw doubt on the validity of audiometric surveillance as a procedure for early detection of noise-induced hearing loss. They also imply that the detection by audiometric tests of true cases of significant threshold shift due to noise is excessively expensive. PMID- 2240991 TI - Exposure to organic solvents--I. A survey on the use of solvents. AB - Organic solvent neurotoxicity is a serious occupational health problem in Denmark. To obtain a precise description of the use of solvents, a questionnaire investigation of a random sample of 1000 companies was made. Information about 2000 liquid products, in particular various kinds of degreasers, paints and lacquers, was collected. Approximately two-thirds of all products contained more than 1% of organic solvents, and of these two-thirds contained more than 20%. A total of 93 different solvents were used, ethanol, industrial gasoline, toluene, isopropyl alcohol and acetone being the commonest. Chlorinated hydrocarbons are not often used now, owing to the replacement of organic solvent-based products by water-based products. PMID- 2240992 TI - Exposure to organic solvents--II. An exposure epidemiology study. AB - The recognition of the 'solvent syndrome' as an occupational disease in Denmark has created a need for mapping the exposure to organic solvents. Exposure levels to organic solvents were measured at 372 representative processes in Danish manufacturing and service industries. Half of the results calculated as sigma(Ci/TLVi) were below 0.25, a quarter between 0.25 and 1, and a quarter above 1. The printing and chemical industries were found to have higher exposure levels than other industries. The commonest processes had the highest exposure levels. A comparison of exposure to organic solvents and incidence of cases recorded as suffering from 'solvent syndrome' in different industries, shows that a causal relationship cannot be disproved by the present findings. PMID- 2240993 TI - Increased isotransferrin ratio and reduced erythrocyte and platelet volumes in blood from thermoplastic industry workers. AB - Ten women (aged 31-61 years) and five men (aged 20-59 years) occupationally exposed to welding fumes of polyacetate containing diethylphthalate in a thermoplastic industry were studied. They had been employed 1-33 years (median: 11 years). Seven women (aged 35-55) and eight men (aged 26-73) acted as unexposed controls. The exposed persons showed increased isotransferrin ratio in blood serum and reduced volumes of erythrocytes and platelets in blood. PMID- 2240994 TI - [Trimetazidine versus betahistine in vestibular vertigo. A double blind study]. AB - The efficacy of trimetazidine (60 mg/day) in vertigo was compared with that of betahistine (24 mg/day) in a three-month double-blind study. Included in the study were only patients with peripheral vertigo associated or not with tinnitus or hearing loss, and excluded were those presenting with symptoms related to retrocochlear or central disease. Out of the 40 patients enrolled, 20 suffered from Meniere's disease; 4 patients either dropped out of the study or were non compliant to therapy and could not be taken into account in the final analysis, which bore on 36 patients (18 treated by trimetazidine and 18 with betahistine). There were no dropouts in the Meniere's disease subgroup (10 receiving trimetazidine and 10 receiving betahistine). Results revealed a better response to therapy with trimetazidine in patients suffering from vertigo, and this was particularly true of the Meniere's disease subgroup (p less than 0.025). Moreover, in the latter subgroup, all patients treated with trimetazidine fully recovered from vertigo spells, while these disappeared completely only in 4 of the patients administered betahistine (p less than 0.005). There was no noticeable difference between the two treatment groups as regards the evolution of the accompanying symptoms and the audiometric or vestibular test results. Clinical acceptability was equally excellent in both treatment groups. Overall, this study allowed to confirm the therapeutical efficacy of trimetazidine in the management of vertigo, as well as establishing the clinical advantage of trimetazidine over betahistine in patients suffering from Meniere's disease. PMID- 2240995 TI - [Trimetazidine versus betahistine in Meniere's disease. A double blind method]. AB - The efficacy and acceptability of trimetazidine (60 mg daily) in the treatment of Meniere's disease were compared with those of betahistine (36 mg daily) during a double-blind study spanning two months. Enrolled in the study were 45 patients (33 treated with trimetazidine, 23 with betahistine) presenting cochlear symptoms (vertigo, tinnitus, hearing loss) compatible with a diagnosis of Meniere's disease. Five patients dropped out of the study (3 in the trimetazidine group did not comply with the therapy and 2 in the betahistine group complained of poor response to the treatment) and were not taken into account in the final analysis, which therefore bore on 40 patients (19 receiving trimetazidine and 21 receiving betahistine). Trimetazidine was found to be significantly more effective than betahistine as far as the overall evolution of the ENT disease was concerned, yielding 79% and 57% improvement rates in each group, respectively (p = 0.027). Complete disappearance of the dizziness attacks was noted in 10 patients out of 19 in the trimetazidine group, versus 5/21 patients in the betahistine group (p = 0.06). There was no statistically significant difference between both treatments, as assessed from other clinical or audiometric criteria. Clinical acceptability was equally excellent in both treatment groups. PMID- 2240997 TI - [Cochlear physiology and physiopathology. Recent data]. AB - Our concept of cochlear physiology has changed so drastically over the last decade that most classical textbooks have become obsolete. This bibliographical inadequacy regarding the functioning of the normal cochlea is particularly disturbing when it comes to addressing patho-physiology problems (hearing loss or tinnitus). What drastic changes have there been, that can justify such need for information updating? These relate primarily to the role of one the two types of sensory cells of the cochlea; i.e., the outer hair cells (or OHC). These cells are endowed with contractile properties and react to tonal impulse by modifying the vibration of the cochlear partition. This "active mechanism" response provokes a localized amplification of the vibration imparting to these classical sensory transducers, or inner hair cells (IHC), their optimal frequency sensitivity and discrimination properties. This new concept alone would suffice to justify our present topic. We chose, however, to insert a general presentation of cochlear physiology, the intent of which is to briefly review the classical data and to analyze in some depth the issues that have drastically changed our knowledge. PMID- 2240996 TI - [A cellular anti-ischemic agent, trimetazidine prevents the deleterious effects of oxygen free-radicals on the internal ear]. AB - Improvement of cochleovestibular symptoms induced by trimetazidine (TMZ) has been evidenced by clinical studies. However, a poor knowledge of the physiopathology and the scarcity of experimental models contributed to making determination of the mode of action of the drugs difficult. We studied the effect, in vitro, of TMZ on the production of oxygen-derived free radicals using, as a biological model, the isolated semicircular canal of the frog. This model allows to exert separate control over the ionic composition of the endo- and perilymphatic fluids. The spontaneous activity of the afferent nerve fibers, as well as the endolymphatic potential, were recorded at rest. Three additional parameters were analyzed, while the semicircular canal was subjected to mechanical stimulation, i.e., ampulla potential, nerve potential and the evoked frequency of action potentials. Free radical generation induced by the administration of phenazine methosulfate (PMS, 10(-5) M, 15 min) into the perilymphatic compartment, leads to a deterioration of the production of endolymph and the release of this afferent neuromediator. Inversely, PMS has no influence whatsoever on the mechanisms of mechanical-electrical transduction. The addition of TMZ (10(-6) or 10(-5) M) in the perilymphatic compartment counteracts the harmful effects of free radicals on the various bioelectric activities. These results suggest that the beneficial action of TMZ observed during treatment of cochleovestibular disorders is due, at least in part, to the anti-oxidizing properties of the molecule of interest. PMID- 2240998 TI - [Acoustic oto-emissions. Clinical uses]. AB - Otoemissions are acoustic signals emitted by the cochlea in response to a short acoustic stimulation (click) that may be recorded with a miniaturized microphone placed within the external auditory canal. They reflect the active mechanisms of the cochlea as they relate to the contractile properties of the outer hair cells, which determine the cochlear properties of sensitivity to and selectivity of frequencies. We have been studying for 5 years the clinical applications of otoemissions in over 500 patients. Otoemissions in 100% of normal ears may be recorded, and the detection threshold is generally 10 dB lower than the psycho physiological threshold. In pathology, otoemissions present a practical interest in the following applications: objective investigation of perception hearing loss, early screening of cochlear disease consecutive to administration of ototoxic drugs, or sound-induced trauma; exploration of Meniere's disease; study of modifications induced by osmotic substances; diagnosis of retrocochlear disease; quick objective assessment of cochlear function in the newborn and the child. PMID- 2240999 TI - [Trimetazidine and degenerative deafness. Effect on hearing and integration]. AB - This study was conducted in order to assess the activity of trimetazidine dosed at 60 mg/day in patients presenting degenerative loss of hearing. Ten centers participated in this multicenter double-blind placebo-controlled trial which spanned 6 months. Included were 251 patients (118 women, 133 men) presenting with pure perception bilateral symmetrical deafness concerning predominantly the acute frequency range. 228 patients terminated the study, including 115 in the trimetazidine group and 113 in the placebo group. The evolution over a 6-month treatment period was significantly better with trimetazidine as regards the following parameters: audibility as assessed by pure-tone audiometry, namely at the acute frequency range (p = 0.002), intelligibility as assessed by speech audiometry (p = 0.008), subjective evaluation of hearing loss and its impact on the patient's social life. Results confirm the value of trimetazidine hearing loss management, based on clinical, subjective criteria as well as audiometric ones. Parameters reflecting best trimetazidine's efficacy were intelligibility and the psychological/behavioral impact of the impairment, allowing for better social integration of the subject. PMID- 2241001 TI - [A multicenter double blind versus placebos study of trimetazidine in tinnitus. A clinical approach to tinnitus]. AB - This multicenter controlled double-blind study versus placebo was carried out in order to determine in which types of tinnitus trimetazidine dosed at 60 mg/day was likely to be of any therapeutical benefit. This trial was conducted over a period spanning 2 months and involved 13 hospital centers. Enrolled were 315 patients presenting with subjective tinnitus. The analysis bore on 290 patients (136 receiving trimetazidine and 154 receiving placebo). Aside from the epidemiological pertinence of this study, results revealed a significantly higher rate of improvement with trimetazidine, as assessed on the basis of subjective clinical criteria, intensity (p = 0.004), periodicity (p = 0.003), and the extent of discomfort (p less than 0.001), as well as audiometric ones. The evolution of the intensity of tinnitus, as measured either by Fowler's comparative scale method or by masking the sick ear, varied significantly (p = 0.007 and p = 0.026, respectively) depending upon whether patients received trimetazidine or placebo. The type of tinnitus which responded best to trimetazidine was recent-onset tinnitus (less than or equal to 2 years) and ischemic disease related tinnitus. PMID- 2241000 TI - [Trimetazidine (Vastarel 20 mg) and electro-acoustic stimulation in the treatment of tinnitus. Apropos of 64 cases]. AB - This open pilot study was carried out with the intent of assessing the pertinence of combining Vastarel 20 mg with electroacoustic stimulation, as opposed to using solely the electroacoustic stimulation method in the management of subjective tinnitus. Enrolled in the study were 64 patients presenting with subjective tinnitus, 50% of which were related to vascular disorders. Following the entry visit (clinical examination, pure-tone audiometry, Metz' test, auditory evoked potentials, CT scans of the internal auditory canal), the patients underwent six 45-minute sessions of electroacoustic stimulation at one-week intervals. Half the patients followed this sole treatment, while the other half was immediately started on Vastarel 20 mg (3 tablets daily) concurrently with the first electroacoustic stimulation session and maintained on this regimen for 3 months. The electroacoustic stimulation (EAS) device used (Tinitop) was operated by emitting a synchronic sound signal mediated by a cask and an electric signal mediated by adhesive electrodes placed in the pretragal area. Results Results were analyzed through history-taking on the 45th and 90th days following the onset of the treatment, subjective improvement of tinnitus being rated from 0% to 100% based on 25% scoring levels (0 = no effect; 100% = complete disappearance of tinnitus spells). At day 45, the proportion of good and very good results (50% improvement or more) was similar (56%), regardless of whether Vastarel 20 mg was or not associated with EAS therapy. On the other hand, the combination of Vastarel 20 mg with masking of tinnitus proved particularly useful in preventing recurrences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241002 TI - [A multicenter double blind versus placebo study of trimetazidine in tinnitus. Measurements of tinnitus]. PMID- 2241003 TI - [The physiopathology of vertigo]. AB - Vertigo is the predominant symptom in labyrinthine dysfunction, and is characterized by an unpleasant modification of the sense of static or dynamic orientation. In order to arrive at a correct clinical interpretation of this symptom and to administer the appropriate treatment, both its etiology and the underlying physiopathological mechanisms need be specified. In the present paper, we shall review a few qualitative concepts, which seem interesting to us and namely concern, on the one hand, the physiopathological mechanisms of vertigo and, on the other hand, the basic principles of the function of peripheral receptors bearing some etiological significance. PMID- 2241004 TI - [A multicenter double blind versus placebo study of trimetazidine in tinnitus. Methods]. PMID- 2241005 TI - [A multicenter double blind versus placebo study of trimetazidine in tinnitus. Epidemiologic analysis of the results]. PMID- 2241006 TI - [A multicenter double blind versus placebo study of trimetazidine in tinnitus. Results obtained after 2 months of treatment]. PMID- 2241007 TI - [The efficacy of trimetazidine in cochleovestibular disorders of ischemic origin. A crossover control versus placebo trial]. AB - In order to assess the efficacy of trimetazidine in the treatment of ischemia related cochleovestibular disorders, we carried out a double-blind placebo controlled study with crossover. Each treatment period spanned 2 months, during which the patients were given either trimetazidine (20 mg tid) or placebo, following a two-week washout period. Enrolled in the study were 45 patients (aged 32 to 69 years) presenting cochleovestibular symptoms (tinnitus, vertigo, hearing loss). Tinnitus occurred in 99.7% of cases, deafness in 88.8%, and vertigo in 68.8% of cases. Pure-tone and speech audiometric data were not modified. Improvement was felt primarily with respect to subjective symptoms. The intensity of vertigo events and the duration of the spells improved much more substantially by trimetazidine and placebo, although the limited number of patients studied did not allow to reach the threshold of significance. The activity of trimetazidine was particularly apparent in relation to tinnitus. The intensity of the latter symptom as well as the degree of discomfort occasioned by it diminished more significantly with trimetazidine than placebo following a 2-month treatment period (p less than 0.05 and p less than 0.02, respectively). These results underscore the therapeutical efficacy of trimetazidine in the treatment of cochleovestibular syndromes, as assessed by a rigorously controlled double-blind trial with crossover versus placebo using a reliable methodology. PMID- 2241008 TI - Delayed endolymphatic hydrops and its relationship to Meniere's disease. AB - Delayed endolymphatic hydrops (EH) can be characterized as having ipsilateral and contralateral types. They are similar in that both have early and late phases of otologic symptoms and that the early phase is a profound hearing loss in one ear. The late phases differ, however, in that the ipsilateral type develops the symptoms of EH (episodic vertigo) in the deaf ear and the contralateral type develops the symptoms of EH (fluctuating hearing loss and/or episodic vertigo) in the hearing ear. In more than half the cases of both types of delayed EH, the profound hearing losses in the early phase are simply discovered to be present in early childhood without a known time of onset. The temporal bones of two patients with contralateral delayed EH show pathologic changes in the deaf ears that are similar to those known to occur in mumps and measles labyrinthitis, whereas the pathologic changes in the hearing ears are similar to those known to occur in Meniere's disease. These observations support the proposition that Meniere's disease may occur as a delayed sequela of inner ear damage sustained during an attack of subclinical viral labyrinthitis occurring in childhood. PMID- 2241009 TI - Arachnoid granulation cerebrospinal fluid otorrhea. AB - A case report and review of the temporal bone (TB) collection in the Department of Otolaryngology at SUNY Health Science Center in Syracuse demonstrated the occurrence of arachnoid granulations (AGs) in the posterior fossa surface of the TB and their role in cerebrospinal fluid (CSF) otorrhea. A large AG responsible for CSF otorrhea in a 64-year-old man was excised with soft tissue repair of the dural defect. Sixteen of 188 TBs (8.5%) in the collection contained 24 AGs ranging in size from 0.07 to 80.65 mm3. Nine AGs (37%) were small (less than 1 mm3) and did not demonstrate enlargement. Twelve (50%) were of intermediate size (2.50 to 9.32 mm3), and three (13%) were large (49.82 to 80.65 mm3). The intermediate and large AGs were associated with bone erosion and a high incidence of communication with a pneumatized mastoid complex (serous otitis media or meningitis). These findings suggest that AGs of sufficient size to produce bone erosion are the primary responsible lesions in adult-onset spontaneous CSF otorrhea. PMID- 2241010 TI - Nerve fiber analysis and the aging process of the vestibulocochlear nerve. AB - Nerve fiber analyses were performed on the human vestibulocochlear nerve stained with Luxol fast blue-periodic acid-Schiff-hematoxylin with use of a combination of an image-analyzer and a computer. The axons were counted and their transverse (cross-sectional) areas were measured in 12 individuals. The average numbers of axons in each vestibular and cochlear nerve were 17,727 and 25,098, and the average transverse areas of their axons were 4.02 and 1.79 microns 2, respectively. Amyloid bodies and intervening Schwann cells in the vestibulocochlear nerve were also counted. The average number of amyloid bodies was 246 per transverse section of the nerve and their average size was 114 microns 2. The average number of intervening Schwann cells was 1,513. Our results indicated that the transverse axonal areas of the cochlear nerve became reduced with age, while the transverse areas of the amyloid bodies in the vestibulocochlear nerve increased with age. The number of vestibular nerve fibers did not seem to change with age. PMID- 2241011 TI - Dimensions of the scala tympani in the human and cat with reference to cochlear implants. AB - The width, height, and cross-sectional area of the scala tympani in both the human and cat were measured to provide dimensional information relevant to the design of scala tympani electrode arrays. Both the height and width of the human scala tympani decreased rapidly within the first 1.5 mm from the round window. Thereafter, they exhibit a gradual reduction in their dimension with increasing distance from the round window. The cross-sectional area of the human scala tympani reflects the changes observed in both the height and width. In contrast, the cat scala tympani exhibits a rapid decrease in its dimensions over the first 6 to 8 mm from the round window. However, beyond this point the cat scala tympani also exhibits a more gradual decrease in its dimensions. Finally, the width of the scala tympani, in both human and cat, is consistently greater than the height. PMID- 2241012 TI - Morphometry of ampullar dark cells. AB - The morphologic characteristics of rat ampullar dark cells were analyzed quantitatively. Four parameters were measured: cell area per micron baseline length, membrane surface density, volume density of intercellular space, and volume density of vacuoles. No statistically significant difference was observed for any parameter, either between dark cell regions of the superior, lateral, and posterior ampullae or between different regions of dark cells within a given ampulla. The membrane surface density of the ampullar dark cells was similar to that reported for principal cells of the cortical collecting duct in the kidney. The volume density of the intercellular spaces of the dark cells was very constant, unlike that reported for epithelia involved in isotonic fluid transport. Vacuoles were found to comprise only a small portion of protoplasm in the dark cells. This new morphometry provides a basis on which to examine the response of ampullar dark cells to differing experimental conditions. PMID- 2241013 TI - Head stability and gaze during vertical whole-body oscillations. AB - To understand head and eye stabilities during upright locomotion, we investigated head and eye movements during vertical whole-body oscillations of various amplitudes (1 to 10 cm) and frequencies (1 to 3 Hz) in both normal subjects (n = 10) and patients with bilateral labyrinthine loss (n = 5). Vertical oscillations produced pitching motions of the head, of which the amplitude was markedly altered by a change in the oscillation frequency or the displacement. Vertical eye movements, being correlated with pitching head movements, were scarcely modified by gaze at 2 and 3 Hz. Acquired bilateral lesions presented deteriorated head stability and physically induced eye movements under stronger stimulations. However, significant increase of head movement upon stepping and suppression of pitching motion upon running, both characteristically found in bilateral lesions, were not reproduced by passive oscillations. Thus, these features during active locomotion may result from imbalance produced by alternate bipedal motions and from adaptation to minimize oscillopsia, respectively. PMID- 2241015 TI - New set of pediatric laryngoscopes. AB - With new advances in pediatric otolaryngology, the awareness of difficulties with existing laryngoscope instruments has become more apparent. The following paper introduces four new pediatric laryngoscopes for use in premature infants, the neonate and infant, the toddler-size child, and the preadolescent-size child. The reasons for the need of new laryngoscopes are explained, and the modifications to existing scopes that are currently employed are discussed. The need for continuous insufflation of oxygen during difficult as well as routine intubation is underscored with reference to the current anesthesia literature. Ventilating techniques in laryngoscopy for the non-respirator-dependent child are discussed. PMID- 2241014 TI - Management of tracheobronchial foreign bodies in children: an update. AB - Tracheobronchial foreign bodies continue to be a source of morbidity and mortality in the pediatric population. Technical advances in anesthesia and equipment have made the removal of these troublesome objects more feasible. Diligence must still be exercised and a coordinated team effort must be employed in order to achieve a satisfactory and safe outcome for the patient. The appropriate use of diagnostic studies and management techniques are discussed. PMID- 2241016 TI - Tracheotomy in the first year of life. AB - Much has been written concerning complications of pediatric tracheotomies, but few studies have reviewed the complication rates of tracheotomies performed in the first 12 months of life. We reviewed the records of 60 patients who underwent tracheotomy in the first year of life between 1976 and 1988. This study includes 30 full-term infants and 30 premature infants, 16 of whom were very low birth weight preterm infants (less than or equal to 32 weeks' gestation and less than 1,500 g birth weight). Overall complication rates were 3% intraoperative, 13% early postoperative, and 38% late postoperative. The early postoperative complication rate in preterm infants was nearly double that of full-term infants. The late postoperative complication rate of patients undergoing tracheotomy for airway obstruction was more than double that of patients requiring tracheotomy for pulmonary indications. Duration of tracheotomy, however, was felt to be the most important factor in the development of a late postoperative complication. PMID- 2241018 TI - Facial nerve monitoring in otologic surgery: clinical indications and intraoperative technique. AB - While identification of the intratemporal portion of the facial nerve is mandatory in most otologic surgical procedures, inadvertent instrumentation, traction, or thermal injury may still result from inaccurate delineation, purposeful avoidance, or false protection of this critical structure. Improved functional preservation of the facial nerve has been achieved in acoustic neuroma surgery through the monitoring of evoked facial electromyographic activity. This technique may also be used during otologic procedures in which facial nerve manipulation is anticipated in the management of recurrent cholesteatoma, temporal bone trauma, congenital deformity, or purposeful access for cochlear implantation. Potential indications for using facial nerve monitoring in contemporary otologic surgery are detailed through illustrative case presentations, and necessary instrumentation and techniques are briefly reviewed. Intraoperative monitoring can assist the surgeon in isolating the facial nerve when chronic inflammation, traumatic injury, or anomalous development has resulted in distortion or absence of microanatomic landmarks. PMID- 2241017 TI - Systems architecture for quantification of dynamic myoelectric and kinematic activity of the human vocal tract. AB - This paper describes a systems architecture useful for scientific investigations that require the acquisition and analysis of multiple, time-synchronous signals in large volume. The architecture has recently been developed by this group to enhance our capability to research and quantify central nervous system function in the production of normal and pathologic speech. The architecture utilizes modern advances in desktop microcomputers and has been designed so that vocal motor control laboratories (or similar settings) with modest funding can more fully participate in comprehensive investigations of speech production. Research experiments organized with this architecture may involve many more subjects and measures than previously possible without significant increases in time and personnel resources. This paper will demonstrate the technique and practicality of this architecture as it is being used to successfully guide research to map hierarchic central nervous system regions of involvement in two speech disorders: spasmodic dysphonia and stuttering. The architecture has broad usefulness to many areas of otolaryngology and health science. PMID- 2241019 TI - Endoscopy of the cochlea during cochlear implantation. AB - We have previously demonstrated that multichannel cochlear implants may be effective in partially obstructed cochleas. In practice, however, it may be difficult to determine whether electrode insertion is feasible prior to attempting it. Initial trials with a flexible fiberoptic otologic endoscope on 10 cadaver temporal bones were previously reported. On the basis of these trials, endoscopy of the inferior segment of the cochlea during cochlear implantation seemed feasible. In the present study, the same endoscope was used on eight subjects undergoing cochlear implantation, six of whom had partially obstructed cochleas. Endoscopy was found to be helpful in visualizing obstructed segments, determining patency after the obstruction was removed, and identifying normal structures of the cochlea. Documentation with videotape and 35-mm photography constitutes the majority of this paper. PMID- 2241020 TI - Titration streptomycin therapy for bilateral Meniere's disease. Follow-up report. AB - Initial reports of the use of parenteral streptomycin for bilateral Meniere's disease (MD) have demonstrated success in reducing the vestibular symptoms and, in some patients, stabilizing hearing. The long-term follow-up (mean, 5.1 years) of 19 patients treated with intramuscular streptomycin for bilateral MD is presented. The amount of streptomycin administered (5 to 50 g) was determined by clinical symptoms and by serial testing of the reduction in the slow-phase velocity on electronystagmography. Episodic vertigo was totally relieved in 12 patients and improved in severity and frequency in an additional 4 patients. Permanent posttreatment dysequilibrium occurred in 47% of the patients treated. The changes in hearing (speech reception threshold) were independent of the therapeutic effect of streptomycin on the vestibular system. The overall results suggest that the intramuscular titration of streptomycin should continue to be considered as one of the therapeutic options in patients with disabling vertigo due to bilateral MD. PMID- 2241021 TI - Retropharyngeal abscess caused by a traumatic perforation of the hypopharynx by a fishbone. PMID- 2241022 TI - Histopathologic grading of salivary gland neoplasms: II. Acinic cell carcinomas. AB - Acinic cell carcinomas display varied cytoarchitectural patterns of growth that should allow for formulation of histopathologic grading. Grading of these carcinomas may serve to identify subsets whose biologic behavior is more aggressive than the usually accepted low-grade behavior of acinic cell carcinomas as a group. To that end, a three-level histopathologic grading scheme is presented. PMID- 2241023 TI - [Transepidermal elimination]. PMID- 2241024 TI - [Perforating folliculitis]. AB - We report the case of a 20-year old male patient without significant familial or personal history who presented with a disseminated papular eruption on the abdomen, flanks and buttocks. The eruption was continual and proceeded by outbreaks, but it was not influenced by seasons. Physical examination of the skin, mucosae and skin appendages was otherwise normal. Histological examination showed all the criteria of perforating folliculitis as described by Mehregan and Coskey. On the basis of our case we would put perforating folliculitis back among the perforating dermatoses. The concept of this curious phenomenon is briefly reviewed; perforating folliculitis is part of the third group of the so-called primary forms. The clinical features are suggestive of the disease, with its small pigmented papules centred around a keratotic plug, forming a permanent disseminated eruption. Histology shows a granuloma facing a lateral perforation of the hair follicle, a pseudo-epitheliomatous epithelial hyperplasia and the presence of hair and keratin debris in the perforation. Various keratolytic treatments have been applied without success; retinoids have not been tried. The main diagnostic and nosological problem is Kyrle's disease. In view of clinical and histological data, many authors regard Kyrle's disease as a major form of perforating folliculitis. Pruritus, ascribed to an underlying illness in Kyrle's disease, is thought to increase the importance of the lesions. The specificity of perforating folliculitis is discussed, but it seems that side by side with secondary forms occurring in recognized diseases, there may be primary forms of perforating folliculitis. Dyskeratosis might be a cause of the perforation. PMID- 2241025 TI - [Anogenital warts in children]. AB - Fourteen cases of anogenital warts in children are reported. Girls were more frequently affected than boys (9/5). Three children had been infected during birth; two had autoinfection from non-anogenital warts; two girls had apparently been sexually abused. In the remaining 7 cases the origin of the warts was unknown. The authors discuss the epidemiological, therapeutic and social implications of this little known but important paediatric pathology, pointing to the possibility of sexual transmission in cases of "apparently" unknown origin. PMID- 2241026 TI - [Dental caries in 2 families with tuberous sclerosis]. AB - Four cases of tuberous sclerosis in two families are presented. We studied the oral manifestations of the disease and we suggest that dental pits should be taken as clinical markers for diagnosis in oligosymptomatic cases. We found that feature in all patients affected by tuberous sclerosis. PMID- 2241027 TI - [Acquired post-inflammatory cutis laxa]. PMID- 2241028 TI - [What is your diagnosis? Pseudosarcomatous fibroma of the skin or atypical fibroxanthoma]. PMID- 2241029 TI - [Livedo reticularis. Review of the literature]. PMID- 2241031 TI - [Treatment of Kaposi's disease]. PMID- 2241030 TI - [Contact hypersensitivity. Cellular aspects]. PMID- 2241032 TI - Free temporoparietal flap in burn reconstruction. AB - A series of 12 patients with deep burns resulting in exposed bones, joints, and tendons, in whom temporoparietal free flaps were used for reconstruction, are presented. Flap loss was 8.3%; good and satisfactory results were achieved in 91.7% of healed defects. Patients with large total body surface area burns are severely compromised, and the use of free flaps requiring prolonged periods of anesthesia and surgery should be a judicious decision. Prior to the availability of free flaps, most of these patients are left with chronic wounds and compromised functional results. Although our experience is limited, we think that in well-selected cases a one-stage reconstruction with free tissue transfer is expeditious, safe, and economical. PMID- 2241033 TI - The medial genicular artery flap. AB - The anatomical basis and clinical applications of the medial genicular artery flap, which is supplied mainly by the cutaneous perforator of the superior medial genicular artery, are herein described. Based on 10 cadaver dissections, the nutrient artery was found to be consistent and was seen to penetrate the deep fascia within a small triangular area bordered by the medial femoral condyle, the vastus medialis, and the adductor magnus tendon. The distal end of the flap must cover the skin over the medial femoral condyle, and the axis of the flap is along the lower half of the sartorius. The proximal end of the flap can be extended safely beyond the midpoint of the thigh. The medial genicular artery flap is thin and can nicely recontour defects around the knee, with an inconspicuous donor site on the medial aspect of the thigh. PMID- 2241034 TI - Chest wall deformities and their correction in bodybuilders. AB - Torn pectoralis major muscles are either treated acutely by orthopedic surgeons or, if neglected, result in deformities of the pectoralis muscle. These deformities are visible, with pectoralis muscle asymmetry, especially on muscle contraction. Bodybuilders prone to this injury accentuate the asymmetry by contracting the pectoralis muscles together. Late repair is not usually possible, and cosmetic improvement relies on removing the bulging, unattached muscles or camouflaging the underlying exposed ribs with a customized implant. Similar customized implants are used to repair pectus excavatum. Techniques must take into consideration the desire for accentuation of the pectoralis muscle with minimal visible scarring. The surgeon and the anesthesiologist should be aware of the possibility of anabolic steroid ingestion in the male body-builder. PMID- 2241035 TI - Refracture reposition of mandibular malunion. AB - The second most frequently injured facial bone is the mandible. For this reason, the incidence of mandibular fractures remains high and will continue to represent a considerable percentage of acute major facial injuries encountered by reconstructive surgeons. Fortunately, to this date, complications have been relatively rare. We present our series evaluating the late sequelae from 135 patients treated by the Division of Plastic Surgery at the University of California, Davis Medical Center, Sacramento, California, for mandible fractures during the period July 1, 1987, to June 30, 1988. From this retrospective record review, we found only six patients who required correction of established traumatic deformities. We report the surgical procedure used in these six patients and an additional two patients referred to our center for surgery. From these eight patients, we delineate the anatomical and functional deformities of mandibular malunion as well as the etiological factors. We will present our surgical method using articulating dental models and occlusal splints, and the application of rigid internal fixation with miniplates and screws for stabilization. All patients in the study presented with either malocclusion or facial asymmetry. We were able to return to each of the patients satisfactory mandibular function and facial symmetry. PMID- 2241036 TI - Two flag flaps based on the supratrochlear vessels for nasal reconstruction. AB - A short forehead or a low hairline sometimes precludes the use of a median forehead flap for reconstruction of defects of the lower nose when both lining and cover are needed. Two flag flaps based on the supratrochlear vessels were used in a patient with a full-thickness alar defect and a narrow, short forehead. PMID- 2241037 TI - Lymphoscintigraphy for melanoma: is it always predictive for lymphatic basin mapping? AB - Therapeutic decision making in treating patients with melanoma is difficult, with very few investigative tools and a lack of treatment options. Surgical extirpation remains the best method for cure and supports discussion in favor of prophylactic regional node dissection for subgroups of patients with stage I disease. In melanoma of the trunk or head and neck, lymphoscintigraphy has reliably provided guidance for resecting the regional lymphatics draining the involved site. This article describes a patient with a melanoma of the posterior neck, with metachronous metastases to the right and left posterior cervical triangles. Lymphoscintigraphy performed in the context of clinically negative nodal regions did not show drainage to either cervical nodal chain. Several explanations are presented, although a false-negative lymphoscintigraphic finding is the only plausible explanation. To our knowledge, this dilemma has not been previously reported, and raises the question of the infallibility of lymphoscintigraphy in predicting lymphatic basin mapping. PMID- 2241038 TI - Successful preexpansion of a free scapular flap. AB - The use of pretransfer tissue expansion of a free scapular flap is described. This technique allows coverage of large defects with good quality skin and tensionless closure of the donor site. PMID- 2241039 TI - Complications with the use of an axillary roll. AB - An axillary roll is frequently used to prevent brachial plexus compression when operating on a patient in the lateral decubitus position. Two complications resulting from the use of an axillary roll are described. Such complications can be avoided by placing a small roll under the upper chest rather than the axillary region. PMID- 2241040 TI - Missed breast cancer in an augmented woman using implant displacement mammography. AB - Good mammography in the augmented patient is often difficult to achieve. A case is described that illustrates that posterior breast tissue is generally better seen with standard compression mammography and that physical examination by the radiologist must accompany mammography. Implant displacement mammography, while helpful, does not eliminate the need for standard compression mammography in selected patients. PMID- 2241041 TI - Umbilical keloid: an early start. AB - A case of umbilical keloid formation following cord separation in an infant is described. Treatment involved excision of the mass and reconstruction of the umbilicus with histological confirmation of the excised lesion. To our knowledge, this is the first report of an umbilical keloid occurring at such an early age. PMID- 2241042 TI - Klippel-Feil anomaly, cleft palate, and bifid tongue. AB - The Klippel-Feil anomaly is a condition characterized by congenital vertebral fusion, which may be associated with a short neck and a low posterior hairline. In the patient presented here, there was congenital cervical fusion, cleft palate, and bifid tongue. The occurrence of cervical fusion and cleft palate has been reported previously, but this is the first report, to the author's knowledge, of these malformations being accompanied by a bifid tongue. The embryological association between Klippel-Feil anomaly and cleft palate has been alluded to on few occasions. Investigators have suggested that the short, fused neck limits movement of the head and thus of the tongue from between the palatal shelves. This report postulates that the mechanism is more complex and that it is based on a change in structural relations between certain key areas involved in the background of palatal shelf elevation. PMID- 2241043 TI - Emergency free flaps to the type IIIC tibial fracture. AB - Type IIIC tibial fractures are complex injuries involving extensive bone and soft tissue devascularization that result in a high percentage of complications and ultimate amputation. An emergency free flap transfer not only may salvage the limb but also may improve the aesthetic and functional results of reconstruction by placing the injured structures in a well-vascularized bed. Two cases of type IIIC tibial fracture were treated in this manner, and we present our experience with a 30-month follow-up of one patient and a 6-month follow-up of another patient. PMID- 2241044 TI - Ready-Stitch: a new device for the closure of skin wounds. AB - Ready-Stitch (Med United Ltd., London, UK) is a new wound closure device that may have considerable advantages over conventional sutures in closing skin wounds. A preliminary study was carried out to ascertain the most appropriate surgical self adhesive tape to use in the construction of Ready-Stitch. Twenty-four skin wounds were then closed with either Ready-Stitch or conventional sutures. Ready-Stitch was much preferred by patients and staff alike, produced good cosmetic results, and may reduce the incidence of wound infection and the likelihood of needle stick injury in hospital staff. PMID- 2241045 TI - Use of a portable floor crane as an aid to resection of the massive panniculus. AB - Resection of the massive abdominal panniculus is technically difficult due to the weight of the tissue and the difficulty in controlling the tissue during surgery. The authors describe the use of a portable floor crane that facilitates resection by reducing the number of assistants required, increasing exposure, and providing for adequate control of the specimen, which assures proper preoperative markings and sterile preparation. Blood loss is reduced, as is operating time. The portable floor crane is usually available in hospital maintenance departments and can be easily modified for intraoperative use. PMID- 2241046 TI - Treatment of mandibular fracture: a hypothesis. PMID- 2241047 TI - Re: Toxicity of cleaning agents for removal of grease from wounds. PMID- 2241048 TI - Re: Psychological considerations in lipoplasty: the problematic or special care patient. PMID- 2241049 TI - Typhoid ileal perforations: a retrospective study. AB - This report examines the characteristics of 124 patients with typhoid ileal perforation treated over a 17-year period ending in 1986. Three adverse prognostic determinants were identified: prolonged fever/perforation interval, prolonged perforation/operation interval and multiple perforations. Simple closure was performed in 74 patients with a mortality of 31.1%, and trimming of the ulcer with closure in 38 patients with a 7.9% mortality. PMID- 2241050 TI - Intra-articular and subcutaneous prilocaine with adrenaline for pain relief in day case arthroscopy of the knee joint. AB - A randomised, double-blind study was conducted to assess the influence of intra articular and subcutaneous prilocaine with adrenaline on postoperative pain in day case arthroscopy of the knee. The time to first dose of oral analgesia postoperatively was significantly prolonged in those patients receiving prilocaine but no significant difference in analgesic effect was demonstrated at 4, 8, and 12 h after operation between the two groups. PMID- 2241051 TI - Dislocated arytenoid: an intubation-induced injury. AB - Three reports describing the morbidity resulting from intubation-induced arytenoid cartilage dislocation are presented. Significant factors contributing to such an injury are: retrognathia, dental malocclusion, a large tongue base and intubation inexperience. We advise that in all patients who undergo a difficult intubation the possibility of arytenoid dislocation should be considered. A ventilating bronchoscope should be readily available upon extubation, to deal with any acute airway problem that may arise. Treatment modalities are discussed and the advantages of a combined anaesthetic and ENT approach highlighted. PMID- 2241052 TI - The association between thyroid neoplasia and intestinal polyps. AB - Recent reports have suggested an association between familial adenomatous polyposis and papillary carcinoma of the thyroid. This report describes four patients, each with intestinal polyps and thyroid or thyroglossal cyst carcinoma. One patient had a medullary rather than papillary carcinoma of the thyroid and in another the intestinal polyps were due to Peutz-Jeghers syndrome. This may indicate a wider association between thyroid carcinoma and intestinal polyps than has previously been recognised. PMID- 2241053 TI - Suturing of digital lacerations: digital block or local infiltration? AB - A prospective trial was carried out to assess the relative efficiency of digital block and local infiltration as methods of anaesthesia when suturing lacerations of the digits. A standard technique and questionnaire were applied to a consecutive group of 62 patients attending the Accident Department of the Bristol Royal Infirmary. Digital block was found to be a more effective technique than local infiltration for anaesthetising digital lacerations. PMID- 2241054 TI - Anaesthetic rooms: current practice in one British health region. AB - In Britain it is traditional that each operating theatre has an adjacent anaesthetic room (1). The implications for equipping current theatre suites and the design of new theatres are wide-ranging. There are no data available on the attitudes of anaesthetists in this country towards the necessity for anaesthetic rooms and the extent of the anaesthetic equipment found in them. This survey in the North West region suggests that all consultant anaesthetists regard the availability of an anaesthetic room as a necessity, and most consider that the current level of vital-signs monitoring equipment in the anaesthetic room is inadequate. PMID- 2241055 TI - Factors influencing peritoneal catheter survival in continuous ambulatory peritoneal dialysis. AB - The success of continuous ambulatory peritoneal dialysis (CAPD) is to a great extent determined by the survival of the peritoneal catheter. The aim of this study was to identify technical factors which influence CAPD catheter survival. A total of 453 CAPD catheters inserted into 310 patients over an 8-year period were analysed. Access to the peritoneum was gained either by an open surgical technique (n = 290) or by a closed technique using a trocar and introducer (n = 163). Data relating to a number of potentially significant risk/benefit factors were analysed using multiple regression analysis (proportional hazards method of Cox). Three factors were found to be independently associated with improved catheter survival. They were: using an open surgical insertion technique, performing a partial omentectomy at the time of catheter insertion and the procedure being performed by a consultant. PMID- 2241056 TI - A new surgical drainage procedure for Baker's cysts. PMID- 2241057 TI - Videofluoroscopy in motor neurone disease prior to cricopharyngeal myotomy. AB - Cricopharyngeal myotomy is a recognised treatment for the dysphagia in motor neurone disease, although the results are sometimes disappointing. In this study, 27 patients with motor neurone disease causing significant dysphagia have been investigated by the technique of videofluoroscopy, in order to determine the nature of their swallowing disability; those patients found suitable have been offered cricopharyngeal myotomy. Of the 27 patients, only seven were found to have cricopharyngeal dysfunction as the predominant disability and, of these, six underwent myotomy, resulting in relief of dysphagia in five, three of whom returned to a near normal diet. Previous studies showed poor overall benefit from cricopharyngeal myotomy. Videofluoroscopy allows accurate patient selection, and a much improved outcome in the selected group. PMID- 2241058 TI - General surgical injuries in survivors of the M1 Kegworth air crash. Nottingham, Leicester, Derby, Belfast Study Group. AB - The general surgical consequences of the M1 Kegworth air crash are described. Considering the severe nature of the injuries sustained by the survivors, surprisingly few required general surgical intervention. Intra-abdominal injuries were rare despite the abdomen's apparent vulnerability to injury; only five laparotomies were performed. However, 30 (34%) of survivors demonstrated significant bruising from lap belts and 13 patients had haematuria. The majority of operations carried out were orthopaedic related. PMID- 2241059 TI - Delorme's operation for rectal prolapse. AB - Between 1981 and 1988 inclusive, 22 patients with full-thickness rectal prolapse presenting to two surgeons in this hospital were treated using the Delorme operation. There was no mortality and morbidity was minimal. Twenty-one patients (95.5%) were cured of prolapse and 19 patients (86.4%) had normal anal sphincter function after the operation. PMID- 2241060 TI - Antiseptic toxicity to breast carcinoma in tissue culture: an adjuvant to conservation therapy? AB - Of 50 patients who had scrape cytology of the excision cavity after conservative surgery for breast carcinoma, 10 (20%) had malignant cells remaining in the cavity recognised by cytology. Of these patients, 18 had histological evidence of tumour at the resection margin, giving an accuracy of the cytology of 84%, a sensitivity of 56%, and a specificity of 100%. When assayed for cytotoxicity against a breast tumour cell line (MCF7) or human fibroblasts, chlorhexidine gluconate was the most effective of eight antiseptics or antitumour agents (100% cytotoxicity at a 1/10,000 dilution) in killing breast tumour cells and had 70% toxicity to human fibroblasts at the same dilution. Hydrogen peroxide appeared to be the most useful agent overall with 94% cytotoxicity to breast tumour cells with only a 12% cytotoxicity to human fibroblasts at a dilution of 1/1,000,000. We suggest that free malignant cells left in the cavity after conservative surgery for breast cancer may be a cause of local recurrence. They can be recognised by scrape cytology at operation and the topical use of antiseptics as cytotoxic agents may be beneficial and warrants further investigation. PMID- 2241061 TI - Primary restorative colectomy in malignant left-sided large bowel obstruction. AB - A series of 18 consecutive patients who underwent primary resection and immediate anastomosis as the treatment for malignant left-sided large bowel obstruction are presented. Intraoperative mechanical preparation of the colon was omitted. There was no clinical evidence of anastomotic dehiscence or wound infection. The mean duration of hospital stay was 11 days. It is suggested that colonic continuity can be restored immediately and safely without mechanical bowel preparation, providing attention is directed to constructing an anastomosis that has a good blood supply and is free from tension. PMID- 2241063 TI - Outpatient carpal tunnel decompression without tourniquet: a simple local anaesthetic technique. AB - Carpal tunnel release was performed under local anaesthesia in 108 wrists of 98 patients. The local anaesthetic (bupivacaine 0.5% and adrenaline) was injected into the subcutaneous tissue down to the flexor retinaculum in the line of the incision. The median nerve was not anaesthetised. No tourniquet was required and analgesia was complete in all but four patients, who complained of some minor discomfort on cutting the flexor retinaculum. Protracted postoperative analgesia was obtained. PMID- 2241064 TI - Comment on presentation of statistics. PMID- 2241062 TI - Testicular obstruction: clinicopathological studies. AB - Genital tract reconstruction has been attempted in subfertile men with obstructive azoospermia (370 patients) or unilateral testicular obstruction (80 patients), and in vasectomised men undergoing reversal for the first (130 patients) or subsequent (32 patients) time. Histopathological changes in the obstructed testes and epididymes, and immunological responses to the sequestered spermatozoa have been studied to gain insight into possible causes of failure of surgical treatment. The results of surgery have been assessed by follow-up sperm counts and occurrence of pregnancies in the female partners. The best results were obtained with vasectomy reversal (patency 90%, pregnancy 45%), even after failed previous attempts (patency 87%, pregnancy 37%). Epididymovasostomy gave good results with postinfective caudal blocks (patency 52%, pregnancy 38%), while postinfective vasal blocks were better corrected by total anatomical reconstruction (patency 73%, pregnancy 27%) than by transvasovasostomy (patency 9%, no pregnancies). Poor results were obtained with capital blocks (patency 12%, pregnancy 3%), in which substantial lipid accumulation was demonstrated in the ductuli efferentes; three-quarters of these patients had sinusitis, bronchitis or bronchiectasis (Young's syndrome). There is circumstantial evidence to suggest that this syndrome may be a late complication of mercury intoxication in childhood. After successful reconstruction, fertility was relatively reduced in those men who had antibodies to spermatozoa, particularly amongst the postinfective cases. Similarly, impaired fertility was found in men with unilateral testicular obstruction and antibodies to spermatozoa. Mononuclear cell infiltration of seminiferous tubules and rete testis was noted occasionally, supporting a diagnosis of autoimmune orchitis; although rare, this was an important observation as the sperm output became normal with adjuvant prednisolone therapy. PMID- 2241065 TI - Junior medical staff and the assessment of trauma. PMID- 2241066 TI - Complications of choledochal cysts in adulthood. PMID- 2241067 TI - Theatre delay for emergency general surgical patients: a cause for concern? PMID- 2241068 TI - The presentation of malrotation of the intestine in adults. PMID- 2241069 TI - [Transfusion and AIDS? Who should be transfused?]. PMID- 2241070 TI - [Limb trauma during parachuting]. PMID- 2241071 TI - [Surgical prevention of radiation injuries of the small intestine]. PMID- 2241073 TI - [A technique of cholecystectomy by minilaparotomy without cutting muscles]. AB - A surgical incision for cholecystectomy is described. It is characterized by its small size, to reduce peritoneal exposure and the resulting postoperative ileus, and the absence of muscular section, to minimize pain and parietal injury. The skin incision is transverse, symmetrical to the midline, 6 cm in length and located 8-10 cm from the xyphoid process. Then a transverse division of linea alba extending 1.5-2 cm on both sides of the two walls of the rectus sheath, without muscular section, is made. Cholecystectomy is commenced at the fundus and continued downwards. PMID- 2241072 TI - [Improvement in the healing of colonic anastomoses by vitamin B5 and C supplements. Experimental study in the rabbit]. AB - To study the effects of vitamins B5 and C on the healing process of colonic anastomoses, 3 groups of 20 rabbits were given daily either placebo (group A), or vitamin B5 (100 mg/kg: group B) or vitamin C (100 mg/kg: group C). After 8 days of supplementation, via a midline incision and under general anaesthesia, 2 colonic segments were removed, and the continuity was restored. On the 3rd post operative day, the rabbits were killed and the anastomoses were removed. Mechanical properties of both normal colon and anastomoses were determined by using bursting pressure tests, number of burst anastomoses, fibroblast count, hydroxyproline concentration and determination by microanalysis of trace element content: Mg, P, S, Ca, Fe, Cu, Zn and Mn. Vitamin B5 (p = 0.03) and vitamin C (p less than 0.01) both decreased the number of burst anastomoses. Furthermore the required bursting pressure values were higher with vitamin C (p = 0.01) than in controls. Both vitamins restored normal Zn levels at the anastomotic site, whereas these levels decreased on the 3rd post-operative day during the normal healing process of colonic anastomosis. Moreover, vitamins B5 and C increased Fe, Cu and Mn levels, which are intimately all involved in collagen synthesis. Vitamins B5 and C enhance the colonic wound healing process in the rabbit, acting together in synergy in vivo as well as in vitro, as previously demonstrated. PMID- 2241074 TI - [Thrombosis of the superior mesenteric artery and perforation of the appendix in a young girl]. AB - Intestinal infarction is due to arterial occlusion or to a thrombosis of the superior mesenteric vein in the case of intra-abdominal sepsis. We report a case unique as far as we know of thrombosis of the superior mesenteric artery due to an appendicular abscess in a young girl without any vascular-risk. PMID- 2241075 TI - [Results of endoscopic ultrasonography in the preoperative assessment of rectal cancer]. AB - Endoscopic transrectal ultrasonography is performed with an ultrasonic transducer (7.5 MHz or 12 MHz) in the tip of a side viewing endoscope. Its accuracy to assess the depth of rectal cancer invasion was prospectively studied in 27 patients. The ultrasonic examination was correct in 23 cases; in 4 cases, the stricturing tumour could not be passed by the probe. The depth of invasion was correctly appreciated in 24 of the 27 cases (accuracy of 89%). The 6 superficial lesions were all correctly detected with endoscopic transrectal ultrasonography. Therefore, endoscopic transrectal ultrasonography appears to be a very promising method in the pretherapeutic staging of rectal cancer. PMID- 2241076 TI - [Contusions of the liver in adults. Initial non-operative management with computerized tomography follow-up is a reasonable therapeutic option. Report of 16 cases]. AB - Nonoperative management of blunt liver injury in adults still remains controversial. From February 1985 through September 1989, 27 patients were treated for blunt hepatic trauma: 11 required immediate operation and 16 (59%) were initially managed nonoperatively after evaluation of intraabdominal injury by computerized tomography. All of these 16 patients were hemodynamically stable and had no significant peritoneal signs. CT criteria for nonoperative management included subcapsular and intrahepatic hematoma, capsular tear or unilobar fracture, absence of large hemoperitoneum, absence of large devitalized liver and absence of other intraabdominal organ injuries. Clinical follow-up, repeated radiologic examinations and surgery confirmed the accuracy of CT. Only 2 patients required delayed operation (12.5%). Serial abdominal CT studies are an integral part of the conservative treatment of blunt hepatic injuries and showed complete resolution of hepatic injuries in the fourteen nonoperated patients in less than six months. No death and no delayed septic or biliary complications were noted. Mean hospital stay was seventeen days for all of the patients (multiple injuries or not) and only ten days for isolated blunt liver injury. These good results depend on identification of candidates for nonoperative management on strict clinical and CT criteria. Nonoperative management of adult blunt liver injury based on these findings is a useful alternative in a selected group of hemodynamically stable patients and decreases the rate of non-therapeutic coeliotomy. PMID- 2241077 TI - [Pathology of the inferior vena cava and liver transplantation]. AB - Pathology of the inferior vena cava is not frequently encountered in the context of liver transplantation. Such a pathology was observed in 7.9% of our recipients, in the pre- intra- and post-operative period. Pre-existing anomalies of the IVC consisted the absence of the retrohepatic vena cava in 7 children with biliary atresia; technical adjustments were quite simple. During the operative period, dissection of the supra-hepatic vena cava was made very difficult in 2 patients with hepatic alveolar echinococcosis complicated by secondary biliary cirrhosis it was necessary to make a trans-diaphragmatic approach to the inferior vena cava. Post-operative inferior vena cava thrombosis occurred in four recipients, in three cases, it was caused by the inadequate size of the graft and major anastomotic discrepancy between the inferior vena cava of donor and recipient and in one case IVC thrombosis occurred in a context of allergy to heparin. Six of the 13 recipients with pathology of inferior vena cava died directly of indirectly because of these problems. Analysis of the causes of this pathology and their possible correction will perhaps allow better results in these patients who undergo liver transplantation. PMID- 2241078 TI - [Treatment of peritoneal carcinomatosis by intraperitoneal chemo-hyperthermia with mitomycin C. Initial experience]. AB - Intra-peritoneal chemo-hyperthermia with mitomycin C was used to treat 9 patients with very advanced gastrointestinal cancers with peritoneal seedings. Resection of the primary tumor was possible in 3 cases. After temporary of closure of the abdominal wall, 90 to 120 minutes of intra-peritoneal chemo-hyperthermia was performed under general anaesthesia with 32 degrees C of systemic hypothermia, via 3 intra-peritoneal drains forming a closed circuit, using 10 mg/l of mitomycin C in 61 of peritoneal dialysate warmed at the inflow temperature of 46 to 49 degrees C. We observed no mortality or morbidity. There were only minor and temporary laboratory side effects and for 6 patients, no malignant cells could be found in the ascitic fluid after intra-peritoneal chemo-hyperthermia. In six patients, we conserved an improvement in the Karnofsky index 3 to 7 months after intra-peritoneal chemo-hyperthermia. These results show that intraperitoneal chemo-hyperthermia with mitomycin C is a safe and reliable treatment for peritoneal seedings in severely advanced gastrointestinal cancers and encourage us to proceed with this new therapeutic modality. PMID- 2241079 TI - [Gastroesophageal reflux and respiratory manifestations: diagnostic approach, therapeutic indications and results]. AB - The authors report a study of 140 patients presenting with a non-allergic respiratory tract disease (121 cases of asthma--19 cases of spasmodic cough). Gastro-oesophageal reflux was detected by 24-hour pHmetry in 86 of these patients. In 34 of them (i.e. 40% of cases), the gastro-oesophageal reflux appeared to be responsible for the initial respiratory tract symptoms. These 34 patients were submitted to a therapeutic trial of high dose anti-H2 therapy for at least two months. Only those patients in whom a marked improvement or even complete resolution of the respiratory tracts symptoms was observed underwent anti-reflux surgery. Out of the 13 patients undergoing surgery, there were two failures and 11 good results after a follow-up of more than 18 months. PMID- 2241080 TI - [Segmentation of the liver and anatomical variants of the portal system]. AB - The authors, who studied 605 human livers according to various techniques, present their own anatomo-surgical conception of human liver segmentation, based on the distribution of the whole intrahepatic Glisson's system, and by dividing the liver into two hemi-livers, right and left (the term "lobe" being reserved, according to Ton-That-Tung, for the classical anatomical lobes): the right hemi liver is subdivided into two segments: anterior and posterior; the left hemi liver is subdivided into three segments: medial (IV), lateral-anterior (III) and lateral-posterior (II); the dorsal segment (I) or the classical Spigel's lobe tends to overlap both half livers (more on the left than on the right). The authors then describe, indicating the percentages, the typical patterns and anatomical variants of intersegmental fissures and the portal system. During the discussion, the authors say that, according to their experience, the right hemi liver segments can be divided into some smaller units: the posterior segment into two subsegments (VI and VII) and the anterior ones into three subsegments (V, VIIIi and VIIIe); and they justify the segmental division of the left hemi-liver. The authors conclude that statistical and analytical study can define a typical anatomical pattern but that, owing to many anatomical variants, it is easier to perform the transparenchymal approach to the vasculo-biliary structures, enveloped in the same Glisson's capsule, rather than to make long and dangerous dissections at the porta hepatis. PMID- 2241081 TI - [Conservative treatment of the spleen. Report of 50 cases]. AB - From 1983 to 1989, 50 patients have been treated by spleen conservation. Traumatism was iatrogenic in 9 cases, caused by public highway accidents in 31 cases, domestic accident in 9 cases and penetrating trauma in one case. Spleen conservation includes: 26 partial splenectomies, 11 cauterisations, 10 sutures, 5 auto-transplantations, and 3 abstensions after laparotomy and little spleen trauma. Three deaths were observed secondary to cerebral trauma, and two complications have been seen: one during the operative solved by total splenectomy, and one rebleeding after splenorraphy, reoperated and splenectomy was performed with good evolution. The follow-up of partial splenectomy showed that splenic remnant keeps an epuration activity. PMID- 2241083 TI - Evidence against linkage of the gene for Usher's syndrome type 1 with group specific component (GC) on chromosome 4. AB - A linkage of the gene for Usher's syndrome with group specific component (GC) on the long arm of chromosome 4 has been suggested by Pelias et al., in 1988. A panel of 38 individuals from 7 kindreds with Usher's syndrome type 1 has been established to test this hypothesis. A negative lodscore was found and close linkage was excluded. PMID- 2241082 TI - [Gonadotropic adenoma. Clinical and hormonal characteristics]. AB - The main clinical and hormonal features of gonadotropin secreting adenomas (GSA) are reviewed through the literature and our personal data. There is still no agreement about their definition and frequency. The most classical clinical presentation is that of men aged 50 years or more, bearing a large pituitary adenoma, the only biological expression of which is a moderately elevated serum FSH level. Female cases are less recognised and are underestimated because the serum LH and/or FSH elevated levels are not informative in menopausal women. The assay of the alpha subunit may help in these cases. In premenopausal women, few of them having been described so far, the GSA may be revealed by an amenorrhea galactorrhea syndrome with a mild hyperprolactinaemia which may result from different mechanisms. The absence of gonadal hyperactivity, and, conversely, the frequent hypogonadism associated with GSA lead the clinician to raise some questions: are all GSA able to secret gonadotropins? How is the bioactivity of the LH and/or FSH secreted by GSA? How reliable are the radioimmunoassays routinely used for measurement of LH and FSH in patient's serum? Furthermore, therapeutical management of GSA is still impaired by the lack of documented medical treatments which could control their growth and prevent their recurrence. PMID- 2241084 TI - Holoprosencephaly in a fetus with a 46,XX,der(7), t(7;8)(q36.1;p12) mat karyotype. AB - In this report we present a female fetus with hemilobar holoprosencephaly and 46,XX,der(7)t(7;8)(q36.1;p12) mat karyotype. The holoprosencephaly-sequence is apparently related with the distal 7(q36.1----qter) deficiency. PMID- 2241085 TI - A paternal balanced translocation [t(7;22)(q32;q13.3)] leading to reciprocal unbalanced karyotypes in two consecutive pregnancies. AB - A family is reported in which a man with a balanced reciprocal translocation [46,XY,t(7;22)(q32;q13.3)] fathered a daughter who was trisomic for the region 7q32----7qter and monosomic for 22q13.3----22qter, and a male fetus who was monosomic for 7q32----qter and trisomic for 22q13.3----22qter. The meiotic segregation of this translocation, as well as the phenotypes of the unbalanced offspring, are discussed. PMID- 2241086 TI - Homozygosity of a 6/18 translocation in a hydatidiform mole. AB - In a complete mole the chromosome investigation revealed a reciprocal translocation 6/18 in a homozygous status. The chromosome polymorphisms of the conceptus could be derived from those of the father. The delineation of the karyotype of the conceptus is discussed. A previous pregnancy of the mother had also led to an abortion of a hydatidiform mole. PMID- 2241087 TI - Duplication 16q12----qter arising from 3:1 segregation in a 46,XX,t(13;16) (q12;q12) mother. AB - A congenitally abnormal female baby was found to have the karyotype 46, XX, +der (16) t (13; 16) (q12;q12) mat. GTG, QFQ, CBG, THA and Ag-NOR banding techniques allowed the identification of the abnormal chromosomes in the proposita and in the translocation carriers through three generations. Duplication 16q resulted from 3:1 segregation in the carrier mother. The hypothesis of a specific meiotic segregation for this translocation is discussed. The phenotypic effects of proximal 16q duplications are analysed together with other four reported cases, which have similar duplicated segment and no other relevant chromosomal abnormality. PMID- 2241088 TI - Retinal cone dystrophy and chromosome 6(q26) deletions. PMID- 2241089 TI - Revision of the chromosome anomalies of the T-cell malignant cell line peer. AB - A high resolution chromosome banding method was applied to define the karyotype of the PEER cell line. It was found significantly different from that previously described, and can be characterized as follows: 46,XX,-4, del(5) (q21q23), del(6)(q14q22), del(9)(p12p21), i(9p), +der(4) rea(4) involving a large duplication of 4q. The cell cycle duration varies in relation to the time after splitting, slow from 0 to 48 h and faster from 48 to 96 h. The average time found was 25 h with durations of 6 and 15 h for G2 and S-phases, respectively. This variable cell cycle led us to change the conditions of BrdU incorporation to obtain a convenient R-banding. According to our own experience, this can be transposed to many other malignant cells to obtain a high resolution chromosome banding. PMID- 2241090 TI - 12q13 fragility in a family with recurrent spontaneous abortions: expression of the fragile site under different culture conditions. AB - A fragile site at the 12q13 band was found in metaphases from lymphocyte cultures of three members of a family. A comparison of the frequency and expression of the fragile site was carried out on cells cultured in RPM-I 1640 with and without BrdU and in 199 media. The fragile site was not typically folate-sensitive, being expressed in standard medium as well as in cultures after exposure to BrdU. PMID- 2241091 TI - Interstitial deletion of the band 4p15.3 defined by sequential replication banding. AB - A 15-year-old boy with intellectual disability was found to have a de novo interstitial deletion in the short arm of chromosome 4. Using GTL banding and sequential replication banding the deleted band was found to be the more terminal of the two G dark sub-bands of 4p15, that is 4p15.3. The karyotype was defined as 46,XY,del(4)(p15.2p16.100). To our knowledge this specific deletion has not been previously described. PMID- 2241092 TI - Joubert syndrome. Review of the fifty-three cases so far published. AB - Joubert's syndrome (JS) is an autosomal recessive disorder, which is characterised by a variable combination of central nervous, respiratory and eye anomalies. We review the clinical characteristics of the 53 so far reported children with Joubert's syndrome, stressing the importance of recognising the syndrome in the neonatal period, in order that specific and effective therapeutic measures be started as soon as possible. PMID- 2241093 TI - Increased adenosine deaminase activity in a patient with cartilage-hair hypoplasia. AB - A boy aged 9 years presenting short stature and recurrent respiratory-tract infections was studied. The clinical and roentgenological pictures allowed the diagnosis of cartilage-hair hypoplasia (metaphyseal chondrodysplasia, McKusick type). Biochemical studies disclosed a four-fold increase in adenosine deaminase activity, but without evidence of anemia. Immunological evaluation showed abnormal cellular but normal humoral immunity. PMID- 2241094 TI - Evaluation of the ras and myc oncoproteins in benign gastric lesions. AB - Ras and c-myc oncoprotein expression was analyzed using specific monoclonal antibodies Y13-259 (for ras p21) and mycl-9E10 (for c-myc p62) in 144 histological sections derived from benign gastric lesions. Increased expression of ras p21 was observed in inflammatory metaplastic, dysplastic, hyperplastic and cystic histological changes, and on the basis of ras p21 staining three distinct histological groups emerged: (i) cystic changes, hyperplastic polyps; (ii) inflammatory gastritis; (iii) metaplastic, dysplastic and adenomatous polyps. Elevated levels of ras p21 expression were found at significantly higher levels than those of c-myc expression in dysplastic lesions. However the expression of the c-myc oncoprotein was less frequent than ras p21 in all other histological types. With the exception of parietal cells, normal stomach mucosa was found to express low levels of both ras p21 and c-myc oncoproteins. PMID- 2241095 TI - Invasive glioma cells in tissue culture. AB - Malignant human glioma is characterized by an uncontrolled cell proliferation and infiltrative growth into the brain. The mechanisms by which invasion occurs are poorly understood. Due to recent development in tissue culture methods, it is possible to study invasion in organotypic coculture systems consisting of glioma spheroids and reaggregated fetal brain cells. Spheroids from well-characterized continuous human glioma cell lines have been tested for invasiveness in this model, which also allows studies of the invasive capacity of glioma cells derived from biopsy material within a week after surgery. Invasion may furthermore be studied in chemically defined media. The methods of studying in vitro glioma invasiveness are reviewed, together with recent results which may throw light upon important mechanisms related to glioma invasion, at the peri- and extracellular level. Mechanisms of glioma cell invasion are discussed with emphasis on the interactive process between cells, growth factors, proteolytic enzymes and the extracellular matrix. PMID- 2241096 TI - Cell death via apoptosis and its relationship to growth, development and differentiation of both tumour and normal cells. AB - Cell death can occur by two possible mechanisms, necrosis or apoptosis. Necrosis is the classically recognised form of cell death and is characterised by high amplitude swelling of the mitochondria, nuclear flocculation and uncontrolled cell lysis. Tissue necrosis is normally seen following severe trauma to cells. The alternative form of cell death is via a programmed sequence of events and is termed apoptosis. Apoptosis occurs under a variety of physiological conditions and cells dying by this process undergo cytoplasmic and nuclear condensation, coupled with cleavage of the cell's DNA into nucleosome size fragments. DNA cleavage is due to the activation of a specific endogenous endonuclease. The cell finally fragments into apoptotic bodies which are engulfed by neighbouring cells and degraded. Apoptosis is an energy requiring process requiring intact energy generating systems, unlike that of necrosis. In relation to malignant disease, apoptosis is the mechanism by which cytotoxic T cells kill tumour target cells; it may also be the mechanism which accounts for the high loss of cells in growing tumour masses. Extensive apoptosis is seen in regressing tumours and also in those treated with chemotherapeutic agents. This form of death may require the activation of specific death genes, although in view of work carried out in this and other laboratories, demonstrating that inhibitors of both protein and RNA synthesis will readily induce apoptosis, this may not be universal. Finally, apoptosis has far reaching implications for the treatment of malignant disease, since only by understanding how cells die will be able to develop more effective means of killing them. PMID- 2241097 TI - A potential role for antisense oligonucleotide analogues in the development of oncogene targeted cancer chemotherapy. AB - The identification of activated oncogenes as the basic biochemical difference between tumour cells and normal cells has opened up the possibility for development of truly tumour specific chemotherapy. It may be hypothesized that malignant cells would revert to a more normal phenotype and might even be triggered into terminal differentiation if expression of the appropriate oncogenes were inhibited. Although, at present, it is not possible to anticipate what form future therapy based upon this approach would take, it is clear that the immediate priority must be to establish the general validity of the hypothesis with a variety of tumour cell types in vitro. For this purpose antisense oligonucleotide analogues appear to offer considerable promise as sequence specific inhibitors of oncogene expression. However, no analogue structure yet devised fulfils all the requirements of an ideal antisense effector in terms of biological stability, cell uptake, non-toxicity, hybridization efficiency and mechanism of action on target nucleic acids. Inhibition of oncogene expression in certain cell types has been reported using antisense oligonucleotides but the technique is not universally applicable and more detailed biochemical investigations of the interactions of oligonucleotides with intact cells are required before improved structures may be developed. PMID- 2241098 TI - Colorectal carcinogenesis: sequential steps in the in vitro immortalization and transformation of human colonic epithelial cells (review). AB - The development of colorectal cancer is an excellent example of the complex multistage nature of carcinogenesis and most colorectal cancers are thought to develop from adenomas. In this paper we have reviewed in vitro models developed in our laboratory for the study of human colorectal carcinogenesis. For these studies epithelial cell lines have been isolated from hereditary and sporadic colorectal adenomas representing different stages in tumour progression. Karyotypic analysis has shown specific abnormalities of chromosomes 1, 7, 14, 17, 18 and 22 to occur in these premalignant adenoma cell lines. The majority of cell cultures derived from small adenomas (less than 1 cm in diameter) senesced whereas the larger adenomas (greater than 2 cm in diameter) were more likely to give rise to immortal cell lines indicating that the acquisition of in vitro immortality occurs at a relatively late stage of colorectal carcinogenesis. Abnormalities of chromosome I have been implicated in tumour progression and in the in vitro immortalization of colorectal adenomas. Furthermore, several stages have been described in the transformation of an adenoma cell line PC/AA to a tumorigenic phenotype. Sodium butyrate and the potent carcinogen N-methyl-N-nitro nitrosoguanidine (MNNG) were used in this transformation. Sodium butyrate is proposed to act as a possible promoter of colorectal carcinogenesis, and MNNG to cause the further genetic changes required for the conversion of the premalignant cells to a carcinoma. Markers to study the progression of an adenoma cell line to a tumorigenic phenotype in vitro include in vitro immortalization, aneuploidy, clonogenicity, resistance to the inhibitory effects of sodium butyrate, anchorage independent growth, ras gene activation, production of active proteinases and tumorigenicity in athymic nude mice. A role for a constitutively produced tumour promoter in colorectal carcinogenesis is discussed together with the possibility that different events are involved in the development of sporadic versus hereditary tumours due to the importance of the microenvironment in hereditary cancer. Our in vitro progression provides the first experimental evidence for the adenoma to carcinoma sequence and the cytogenetic evidence suggests that it is relevant to in vivo carcinogenesis. PMID- 2241099 TI - Response of human immunodeficiency virus long terminal repeat to growth factors and hormones. AB - We have employed a recombinant plasmid, pBHIV1, carrying the long terminal repeat (LTR) of the human immunodeficiency virus-1 (HIV-1) linked to the reporter chloramphenicol acetyl transferase (cat) gene and to the aminoglycoside phosphotransferase (aph) gene as a selectable marker. We have introduced pBHIV1 in rat 208F and human MRCSV40TGR fibroblasts and obtained stable geneticin resistant RFBHIV1-1 and SVTGHIV-1 transfectant cells respectively. Both RFBHIV1-1 and SVTGHIV1-1 cells express CAT activity from the HIV LTR promoter. The response to insulin, epidermal growth factor, hydrocortisone and dexamethasone was studied on the LTR regulated CAT activity in both cell lines. It was found that, at optimal concentrations, insulin, epidermal growth factor and hydrocortisone regulate positively the expression of CAT from the HIV LTR in rat RFBHIV1-1 but not in human SVTGHIV1-1 cells. On the other hand dexamethasone at 10(-5) M stimulated CAT activity in both types of cells. PMID- 2241100 TI - Genetic regulation of metastatic progression. AB - Metastasis is a complex process which results in the growth of tumor cells at sites distant from the primary neoplasm. It is likely that many of the large number of biological changes associated with metastatic ability are controlled through alterations in the expression of a relatively small number of key genes usually referred to as cellular oncogenes and tumor suppressor genes. These genes are normally required for the regulation of growth-related processes in the cell, and alterations through mutations and/or expression are important in establishing metastatic properties of malignant cells. In this article, we review evidence indicating that oncogenes play an important role in metastatic spread, and we have placed emphasis on studies with the ras oncogenes. Metastatic progression is dependent upon an accumulation of multiple genetic changes in malignant cells. Therefore, we have also briefly addressed the related questions of altered growth factor regulation, and the cooperative interactions observed between dominantly acting oncogenes and between these genes, and tumor suppressor genes. PMID- 2241101 TI - Enzyme kinetics of thymidine kinase isoenzymes of Ehrlich ascites tumour. AB - Three isoenzymes of thymidine kinase (TK) identified on Ehrlich ascites tumour corresponding to pl values of 5.3, and 6.9 and 8.3 were studied with respect to their kinetic properties. The isoenzymes were separated by thin-layer isoelectric focusing and measured in the presence of thymidine (TdR) as substrate, adenosinetriphosphate (ATP) as phosphor donor and deoxythymidinetriphosphate (dTTP) as inhibitor. Exponentially growing cells and growth inhibited cells were used with high proportions of the isoenzymes at pl values of 6.9 and 8.3, and 5.3 respectively. The concentrations of the former were further enhanced by the use of S-phase cells isolated by elutriator centrifugation. The isoenzymes were identified as TK1-onc, earlier found in human leukemia cells. In order to confirm the existence of TK1, particular at pl value 5.3, the ability of the isoenzymes to use different phosphor donors (ATP and uridinetriphosphate (UTP)) and substrates (TdR and deoxycytidine (dCdR) was also studied. These results showed that the isoenzymes at pl 6.9 and 8.3 correspond to TK1, while the isoenzyme at pl 5.3 is heterogeneous. Further, high resolution isoelectric focusing confirmed the existence of two isoenzymes at pl values of 5.1 and 5.3, representing mitochondrial (TK2) and cytoplasmic (TK1) isoenzymes. PMID- 2241102 TI - Influences of various substrata on morphology, motility and invasiveness of rat tumour cells. II. Studies on the highly metastatic variant BSp 73 ASML. AB - In a previous paper we studied the influences of the basal lamina and its components on the invasive but nonmetastatic variant BSp 73 AS of a rat pancreatic adenocarcinoma. In continuation of this publication we used the in vivo strongly metastasizing but hardly invasive variant BSp 73 ASML. On plastic or glass supports the low passaged ASML-cells grew separately, spread very scarcely and remained passive. Compared to these standard culture conditions, the behaviour of the tumour cells could be modified by biomaterials like collagen type I/III and type IV, fibronectin, laminin, matrigel, lens capsule and basal lamina. On these substrata (compared to plastic supports) the ASML-cells showed increased spreading, filopodial outgrowth and secretion of membrane vesicles. Only signs of motility as well as penetration of the biomatrices could be observed. Interestingly, highly passaged ASML-cells displayed an increased tendency to spread even on plastic. Under dynamic conditions these cells even failed to adhere. Obviously the biomatrices in vitro as well as long-term passaging are able to lead the ASML-cells partly to reactivate the behaviour that is characteristic of malignant tumour cells. Additionally, there is some evidence that the ASML-cells in vitro can strongly respond to chemotactic stimuli by exhibiting both flattening and translocative motility. PMID- 2241103 TI - Epidermal growth factor receptors in human tumors of the central nervous system. AB - Epidermal growth factor receptors (EGF-R) have been measured in human tumors of the Central Nervous System (CNS) by 125I EGF ligand binding. High affinity receptors (Ka congruent to 1 x 10(9) M-1) were detected in nearly all individual specimens of meningiomas and tumors of glial origin (astrocytomas, glioblastomas). The phosphotyrosine kinase activity associated with the EGF-R was evaluated by measuring the incorporation of gamma 32P-ATP, after immunoprecipitation of the receptor with the monoclonal antibody EGFRI. A good relationship was observed between the EGF-binding capacity and the autophosphorylation of the receptor, indicating that in most cases functional molecules of EGF-R were expressed on the tumor membranes. In the group of meningiomas, no relationship could be established between the EGF-R level and the histopathology of the tumors. Astrocytomas exemplify a progression of malignancy, from benign (low grade astrocytomas) towards an increased malignant phenotype (glioblastomas). In this group, our observations indicate a positive relationship between the EGF-R level and phosphokinase activity and the degree of malignancy. PMID- 2241104 TI - Antitumor activity of a novel synthetic polyamine analogue, N,N'-bis-[3 (ethylamino)-propyl]-1-7-heptane diamine: potentiation by polyamine oxidase inhibitors. AB - The requirement of the natural polyamines, putrescine, spermidine and spermine, for cell growth suggests that appropriate structural analogues of these compounds could serve as potential antiproliferative agents acting via polyamine antagonism. In this investigation, the antiproliferative activity of N, N'-Bis[3 (ethylamino)-propyl]-1-7-heptane diamine (BEPH), a synthetic polyamine analogue, was investigated employing HeLa cells in culture and L1210 leukemia in mice. BEPH inhibited the growth of HeLa cells with an IC50 of 0.25 microM during a four day culture period. This concentration of the compound was cytotoxic to the cells as evidenced by an 80% reduction in cloning efficiency. Only marginal changes in intracellular polyamine concentrations were observed during incubation with 0.25 microM BEPH. In both HeLa cells and L1210 cells in culture, incorporation of radioactive precursors into DNA, RNA and protein were reduced by BEPH. Inhibition of protein synthesis was discernible prior to inhibition of RNA and DNA in these cells. In mice inoculated i.p. with 10(5) L1210 cells on day 0, i.p. administration of 10.0 mg/kg of BEPH qd(X5) beginning on day 1 prolonged the survival time by 84% compared to controls. The same dose of the compound, in combination with 10.0 mg/kg of N,N'-bis-2-3-butadienylputrescine, an inhibitor of the polyamine catabolizing enzyme polyamine oxidase (PAO), produced a 100% cure rate. Similar results were obtained when BEPH was combined with N-methyl-N'-2-3 butadienylputrescine, another PAO inhibitor. Furthermore, animals cured of the leukemia by the combination chemotherapy were resistant to a subsequent challenge with L1210 cells, indicating the development of tumor "immunity". The striking antitumor activity along with the development of tumor immunity indicate that synthetic polyamine analogues have potential for development as antineoplastic agents. PMID- 2241105 TI - Comparative in vitro binding characteristics and biodistribution in tumor-bearing athymic mice of anti-ovarian carcinoma monoclonal antibodies. AB - The interactions of four monoclonal antibodies (OV-TL 3, OV-TL 16, OV-TL 30 and OC 125) with ovarian carcinoma cells (NIH: OVCAR-3) were compared in vitro as well as in a nude mouse model. The affinity constants of the antibodies ranged from 1.0 X 10(9) M-1 (OC 125) to 3 X 10(9) M-1 (OV-TL 30). The cell binding kinetics of the antibodies were studied in vitro: OV-TL 30 associated fastest (50% binding after 25 min), OV-TL 3 and OV-TL 16 associated more slowly (50% binding after 75 min), while the association of OC 125 was slowest (50% binding after 120 min). Dissociation rates of the antibodies also differed: OC 125 displayed the lowest dissociation rate (t1/2 = 360 min). The OV-TL antibodies showed a faster, biphasic dissociation characteristic. The biodistribution of the radioiodinated antibodies in NIH:OV-cAR-3 xenograft-bearing athymic mice, following intravenous injection, was compared. Highest tumor accumulation 48 h p.i. was found with OV-TL 3 (13.3 +/- 2.1% ID/g) and OV-TL 16 (11.0 +/- 2.0% ID/g), while the uptakes of OV-TL 30 and OC 125 were markedly lower (4.9 +/- 0.9% and 6.0 +/- 0.9% ID/g, respectively). The fact that in this experimental model the in vivo tumor accumulation of OV-TL 3 and OV-TL 16 was approximately twice as high as the tumor accumulation of OC 125 could not be fully ascribed to parameters of the antibodies determined in vitro (immunoreactive fraction, affinity constant, antigen density, association and dissociation rate). It is suggested that the antibodies OV-TL 3 and OV-TL 16 are suitable tools for clinical radioimmunodetection of ovarian carcinomas. PMID- 2241106 TI - Factors in prostate cancer metastasis. AB - Death related to prostate cancer is invariably due to the tumor metastasis (to lungs, skeleton and lymph nodes). Tumor cell metastatic behaviour is still poorly understood. The R3327 prostate tumor model in the male Copenhagen rat offers an opportunity to investigate the different aspects of metastatic processes in vivo and to evaluate effects of current and new treatment approaches. Lymphatic spread of cancer cells can be measured by determining volume of local load in successive draining lymph node stations. Surgical removal of primary tumor and inguinal lymph node shows that lymphatic metastasis in the R3327-MATLyLu tumor variant is a continuous progressive phenomenon, which starts already in early stages of tumor growth after subcutaneous transplantation. Spread to the lungs can be quantified by enumeration of macroscopically visible pleural lung colonies. Metastatic spread to the lungs can be mimicked by intravenous injection of monodispersed tumor cell suspension. Within 10 days pleural tumor colonies become visible. Effects of different agents and treatments like chemotherapeutic drugs, heparin, surgery and high energy shock wave (HESW) treatment have been described using these methods. Recently, metastasis to the vertebral column was induced by temporal occlusion of venous blood flow through the caval veins while injecting tumor cells in the lateral tail vein. The resulting osteoblastic metastatic lesions in the lumbar vertebrae and the concomitant spinal cord compression led in time to the loss of motoric and sensory function of the hind legs. These observations permit investigation of the mechanisms of bone metastasis based on biological functions, i.e. sensory and motoric function of the hind legs. Finally, it can be said that the various variants of the R3327 rat prostate tumor offer an appropriate model to study various aspects of prostate cancer and metastasis. PMID- 2241107 TI - Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). AB - Prostate cancer is a major cause of cancer death among males, yet little is known about its etiology. We hypothesize that Vitamin (Hormone) D deficiency may underlie the major risks for prostate cancer, including age, Black race, and northern latitudes. These factors all are associated with decreased synthesis of Vitamin D. Mortality rates from prostate cancer in the U.S. are inversely correlated with ultraviolet radiation, the principal source of Vitamin D. This hypothesis is consistent with known antitumor properties of Vitamin D, and may suggest new avenues for research in prostate cancer. PMID- 2241108 TI - Phenotypic stability of B16-BL6 melanoma exposed to low levels of tyrosine and phenylalanine. AB - We previously demonstrated that tyrosine (Tyr) and phenylalanine (Phe) restriction suppresses metastatic heterogeneity of B16-BL6 (BL6) melanoma and selects for tumor variants with decreased metastatic potential. In this study, we investigate stability of this Tyr- and Phe-modulated tumor phenotype by sequentially transplanting BL6 in vivo into mice fed Low Tyr and Phe Diet. Metastatic potential of BL6 is suppressed after one subcutaneous passage. Suppression is unlikely to result from inhibition of tumor growth, since growth in vitro is significantly increased. The metastatic potential of the Tyr- and Phe modulated tumor is unstable after in vivo passage, and lung colonizing ability is regenerated after ten in vivo passages. Conversely, the antimetastatic effect of Tyr and Phe restriction is stable after prolonged in vitro passage. The metastatic potential of tumors from mice fed Normal Diet is unstable after long term in vitro culture. Sensitivity to adriamycin of BL6 from mice fed Low Tyr and Phe Diet is increased and is not altered by change in metastatic potential. PMID- 2241109 TI - Differentiation-related alterations in the plasma membranes of chemically transformed murine fibroblasts. AB - One of the pathways of action of the differentiation-inducing agent DMF, in chemically transformed AKR-MCA fibroblastic cells, is through the concurrent restoration of the synthesis of the cell-surface adhesion molecule fibronectin and receptors for fibronectin. In order to identify plasma membrane components that are intimately associated with the induction of differentiation by DMF in the AKR-MCA cells, we have purified, characterized and compared the plasma membranes prepared from DMF treated and untreated AKR-MCA cells and from DMF treated and untreated AKR-2B cells (untransformed control cells). While DMF was found to have a non-discernible effect on the plasma membranes of the untransformed AKR-2B control cells, it restored the expression of several major AKR-2B associated plasma membrane proteins to the transformed AKR-MCA cells. These included major plasma membrane proteins of molecular weight 46 and 38 kilodaltons which were identified by one-dimensional SDS-PAGE, and two other major silver staining proteins identified by two-dimensional gel electrophoresis. Plasma membrane carbohydrate moieties were also analyzed by 125I-lectin probes following SDS-PAGE fractionation and electrophoretic transfer of plasma membranes to nitrocellulose. Differences in the radiolabeled Con A and RCA 1 binding profiles were observed between the untransformed and transformed cells. DMF induced an overall restoration of the untransformed AKR-2B associated lectin binding profiles to the differentiated AKR-MCA cells. This study identified several plasma membrane proteins and lectin binding carbohydrate moieties, the qualitative or quantitative alterations of which were intimately associated with chemical transformation and differentiation induction of the transformed cells. PMID- 2241110 TI - Differentiation can convey resistance to transformation by activated ras oncogene. AB - Nonterminal cellular differentiation has recently been shown to induce transformed cells to revert to a benign state and to become resistant to retransformation by chemical and physical carcinogens without limiting their proliferative potential. Nonterminal differentiation also induces native 3T3 T mesenchymal stem cells to become resistant to transformation induced by numerous chemical and physical carcinogens. This characteristic has been designated anticancer activity. In the current study, experiments show that cells expressing differentiation-associated anticancer activity are also resistant to transformation by the activated ras (EJras) oncogene. Resistance to EJras transformation is shown not to result from a reduced efficiency of DNA transfection nor from reduced integration of EJras into the genome. Moreover, the results show that the EJras oncogene product can be expressed in cells demonstrating anticancer activity. Nonterminal cellular differentiation, therefore, induces resistance to transformation caused by activated ras oncogene as well as to numerous physical and chemical carcinogens. PMID- 2241111 TI - Growth factor modulation of metastatic lung colonization. AB - Altered production and response to growth factors is often involved in neoplasia but little is known about their effect on the dissemination of tumors. Therefore, we have examined the effect of growth factors on metastatic lung colonization. Autocrine induction of the metastatic phenotype was demonstrated in NIH-3T3 cells transformed by a signal peptide-bFGF gene but not bFGF in the absence of the signal peptide. In addition, exogenous growth factor regulation of metastasis was demonstrated. Treatment of ras transformed C3H-10T 1/2 cells and ras or src transformed NIH-3T3 cells with bFGF prior to intravenous injection resulted in potent inhibition of metastatic potential. Stimulation of v-fms transformed cells by the natural fms-ligand, CSF-1, resulted in potent stimulation of metastatic behavior in freshly plated or refed cells, whereas following autocrine conditioning of the medium, the metastatic properties of these cells were sensitive to inhibitory effects of CSF-1. These observations indicate that specific growth factors can regulate the metastatic phenotype and, depending on the oncogenes responsible for cell transformation and autocrine conditioning, these effects can be either stimulatory or inhibitory. PMID- 2241113 TI - Stroke in pediatric acquired immunodeficiency syndrome. AB - In a 4 1/2-year period, 4 of 68 children in a longitudinal study of neurological complications of human immunodeficiency virus (HIV) infection had clinical and/or neuroradiological evidence of stroke, yielding a clinical incidence of stroke in this population of 1.3% per year. During this period, 32 subjects died, and permission for autopsy was granted in 18 of the patients, including 3 of 4 who had clinical evidence of stroke. The prevalence of cerebrovascular pathological features in our consecutive autopsy series was higher than the clinical incidence. At autopsy cerebrovascular disease was documented in 6 (24%) of 25 children with HIV infection, including all 3 children who had clinical evidence of stroke. Four patients had intracerebral hemorrhages, 6 patients had nonhemorrhagic infarcts, and 3 had both. Hemorrhage was catastrophic in 1 child and clinically silent in 3 children, all of whom had immune thrombocytopenia. One child had an arteriopathy that affected meningocerebral arteries. In another child, the arteries of the circle of Willis were aneurysmally dilated. Two children had coexisting cardiomyopathy and subacute necrotizing encephalomyelopathy with vascular proliferation. These results suggest that stroke should be considered when children with HIV infection develop focal neurological signs. PMID- 2241112 TI - CA-125 monitoring in the management of ovarian cancer. AB - In 100 ovarian cancer patients serum CA-125 was monitored during treatment and follow-up to verify the prognostic value of its pre-surgery marker level and the usefulness of the test for disease monitoring. A low pre-operative CA-125 was not associated with improved survival or progression-free survival. A significant survival advantage was evident for patients in whom the marker had decreased during treatment, compared to patients in whom the antigen remained unchanged or increased. In 40 patients CA-125 was measured before second look laparotomy: the marker was negative in 100% of patients in, pathological complete response and in 53.5% of patients with residual disease at second look. A marker increase was evident in 32 of 41 patients with either progressive or recurrent disease, and in 17 patients the CA-125 increase was documented from 1 to 9 months before clinical evidence of progression. The pre-operative level of CA-125 did not appear to be of prognostic value. However, the monitoring of CA-125 during treatment and follow-up can provide a reliable method of assessing response and prognosis. CA 125 monitoring is particularly useful for early detection of recurrence. PMID- 2241114 TI - Myasthenic thymus and thymoma are selectively enriched in acetylcholine receptor reactive T cells. AB - We compared T-cell proliferative responses to acetylcholine receptor (AChR) and to purified protein derivative (PPD) (of tuberculin) of hyperplastic thymus, thymoma, and blood cells from patients with myasthenia gravis (MG). Hyperplastic MG thymus cells gave significantly higher and more consistent responses to AChR than parallel cultures of autologous blood cells, whereas responses to PPD showed an opposite trend. Thus there was a preferential localization of AChR-reactive T cells in the hyperplastic MG thymus. Furthermore, there was a strong correlation between blood and thymus cell responses to PPD (but not to AChR), arguing that the hyperplastic MG thymus contains a sample of sensitized peripheral T cells. By contrast, both AChR- and PPD-responsive T cells were almost undetectable in thymus from nonmyasthenic patients, which is evidently much less receptive to circulating T cells. Cells from MG thymomas showed the highest stimulations by AChR but did not consistently react to PPD. However, the uninvolved thymus adjacent to these thymomas behaved almost identically to the hyperplastic samples described above. Our interpretation is that AChR-specific T cells are initially sensitized in the MG thymoma but are selectively trapped in the hyperplastic thymus after being primed elsewhere. PMID- 2241115 TI - Auras and subclinical seizures: characteristics and prognostic significance. AB - The characteristics and prognostic significance of subclinical seizures and independent auras were studied in 40 patients with partial epilepsy who had long term electroencephalographic (EEG) monitoring with intracranial electrodes. Focal, restricted subclinical seizures were noted in 23 patients, and 11 patients experienced auras that were accompanied by ictal EEG discharges. Auras and subclinical seizures usually were identical in EEG appearance, but were distributed differently among patients. The subclinical seizures and auras usually had the same origin as complex partial seizures, but did not always reliably indicate complex partial seizure origin. Subclinical seizures and auras were of favorable prognostic significance for patients undergoing temporal lobectomy. A majority (greater than 80%) of individuals with subclinical seizures and auras were free of complex partial seizures after surgery, whereas a minority (29%) of patients without subclinical seizures and auras became free of complex partial seizures. PMID- 2241116 TI - Increased MEPP frequency as an early sign of experimental immune-mediated motoneuron disease. AB - Intracellular recordings of miniature end-plate potentials were performed in extensor digitorum longus muscles from guinea pigs with experimental immune mediated motoneuron destruction. In the early stages of the disease, the miniature end-plate potential frequency was elevated compared to that in control and normal animals. The amplitude and time course of the miniature end-plate potentials as well as the resting potential of the muscle fibers were not altered, which implies integrity of the postjunctional membrane. The increase in frequency of miniature end-plate potential reflects an increase of basal acetylcholine release and documents dysfunction of the presynaptic terminal of the neuromuscular junction. The increased frequency was associated with high levels of antimotoneuronal IgG in the blood and the presence of IgG at motor end plates. These data suggest that the presynaptic terminal of the neuromuscular junction may be involved in the immune attack in animal models of motoneuron degeneration. PMID- 2241117 TI - Anoxic injury of mammalian central white matter: decreased susceptibility in myelin-deficient optic nerve. AB - The rat optic nerve, a typical central nervous system white matter tract, rapidly loses excitability when it is exposed to anoxia and is irreversibly damaged by prolonged anoxia. Neonatal optic nerve is extremely resistant to anoxia-induced dysfunction and injury; the adult pattern of response to anoxia appears between 10 and 20 days postnatal, that is, during the period of oligodendroglial proliferation and myelination. To test the hypothesis that myelination, or associated events, confer anoxic susceptibility on developing white matter, we analyzed the effects of anoxia on the myelin-deficient (md) strain of rat. Acutely isolated optic nerves from 19- to 21-day-old md rats and control optic nerves from unaffected male littermates were maintained in vitro at 37 degrees C, and exposed to a standard 60-minute period of anoxia. The supramaximal compound action potential was recorded and amplitude of the compound action potential, expressed as % of amplitude before anoxic exposure, was determined. The compound action potential was nearly abolished within 3 to 6 minutes after onset of anoxia in control optic nerves, while optic nerves from md rats displayed a slower decrease in compound action potential amplitude during anoxia, with a distinct action potential present even after 60 minutes of anoxia. Optic nerves from md rats showed significantly greater recovery of compound action potential (71 +/- 25%) than did control optic nerves (33 +/- 21%; p less than 0.02) after 60 minutes of anoxia. These findings support the hypothesis that myelination, or changes associated with it, may be important in the development of anoxic susceptibility in central white matter. PMID- 2241118 TI - Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis. AB - Monoclonal antibody immunocytochemistry was used to examine spinal cord and muscle in amyotrophic lateral sclerosis for changes that would indicate ongoing or potential immune activity. Increased expression of class I and II major histocompatibility complex (MHC) antigens was seen in the affected areas of spinal cord. New MHC expression was concentrated in phagocytes, particularly in degenerating white matter in which they were dispersed in the tissue and also packed around blood vessels. MHC antigen was not revealed in motor neurons or skeletal muscle fibers. An anti-pan-T-cell monoclonal revealed small numbers of T cells in degenerating white matter. Similar changes have been seen in other neurodegenerative disorders. They suggest a potential for (secondary) cell mediated activity in the affected areas rather than an ongoing MHC-restricted T cell response. Vessel-associated phagocytes may be a source of antigen to peripheral lymphoid tissue, stimulating production of the autoantibodies that have been described. PMID- 2241119 TI - Cerebral circulation and oxygen metabolism associated with subclinical periventricular hyperintensity as shown by magnetic resonance imaging. AB - A combined magnetic resonance imaging and positron emission tomography study was performed on 21 patients with cerebrovascular risk factors but without neurological abnormalities. Our purpose was to investigate the hypothesis that periventricular hyperintensity (PVH) reflects ischemia. Periventricular hyperintensity was evaluated with a method we devised, and cerebral circulation and oxygen metabolism were evaluated with the oxygen-15 steady-state technique. We concluded that the brain with severe periventricular hyperintensity had abnormal circulation, although oxygen metabolism was not measurably affected. The role of a compensation mechanism under conditions of decreased oxygen supply was considered. PMID- 2241120 TI - Drop attacks with Meniere's syndrome. AB - We report the clinical features of 12 patients with drop attacks associated with Meniere's syndrome. Each described a sensation of being pushed, thrown, or knocked to the ground or a sudden illusion of movement of the environment that led to a fall. These episodes were not accompanied by symptoms of their typical attacks of Meniere's syndrome. The drop attacks occurred early and late in the course of the disease; they were the initial manifestation in 1 patient. In the majority the episodes spontaneously remitted, although Meniere's syndrome continued to progress. These attacks probably result from a sudden mechanical deformation of the otolithic membrane of the utricle or saccule due to pressure gradients within the inner ear. They are important to recognize because their prognosis is relatively benign compared to other causes of drop attacks. PMID- 2241121 TI - Electroencephalography laboratory diagnosis of prolonged QT interval. AB - Patients with prolongation of the QT interval are at risk for significant neurological morbidity and mortality secondary to ventricular tachyarrhythmias. These patients frequently undergo electroencephalographic (EEG) examination to evaluate episodes of loss of consciousness, which may be associated with convulsions. Electrocardiogram recording as a part of the EEG is a simple and common practice, but analysis for possible QT prolongation is not routinely performed by electroencephalographers. This is, in part, due to the fact that while calculation of the corrected QT interval is straight forward, a calculator is generally required. A nomogram that is presented simplifies determination of the corrected QT interval, facilitating diagnosis of prolongation of the QT interval in the EEG laboratory. PMID- 2241122 TI - Spinal cord compression with paraplegia in xanthomatosis due to normocholesterolemic sitosterolemia. AB - A 48-year-old woman with a 30-year history of tendinous xanthomatosis developed paraplegia. The magnetic resonance image revealed extramedullary tumors. The analysis of her sera and tumors revealed increased amount of plant sterols, especially sitosterol, and the diagnosis of sitosterolemia was made. This is the first reported case of a patient with sitosterolemia who had the neurological complication of spinal cord compression due to extramedullary sitosterolemic xanthomas. PMID- 2241123 TI - Recurrent seizures in children with Shigella-associated convulsions. AB - Fifty-five children with Shigella-associated convulsions were followed prospectively to investigate their risk of subsequent febrile or nonfebrile seizures. The duration of the follow-up period was between 6.9 and 14.1 years (9.7 +/- 3.1 years). No case of nonfebrile seizures and only 2 cases (3%) of subsequent febrile seizures were observed during this period. We conclude that although febrile and Shigella-associated convulsions share many clinical features, the natural history of these two conditions seems to be distinctly different. Shigella-related convulsions are not associated with an increased incidence of subsequent febrile or nonfebrile convulsions. PMID- 2241124 TI - Ergotamine headache mistaken for temporal arteritis. PMID- 2241125 TI - Report of unusual HIV transmission demands attention, not legislation. PMID- 2241126 TI - Hemophiliac patients in surgery. Implications for perioperative nurses. AB - The introduction of plasma clotting factor concentrates has changed the treatment of patients with clotting factor deficiencies dramatically. They have enabled hemophiliacs to be independent and have some control over the management of their disease as informed participants. This has played a role in shortening the number of hospitalizations that hemophiliacs may have to endure and to decrease the length of stay when they are admitted. Additionally, staff who care for these patients do not need to be afraid of the disease if they are aware of the disease process and the therapy available for its amelioration. PMID- 2241127 TI - Fractures. Types, treatment, perioperative implications. PMID- 2241128 TI - Perioperative nurse internship. Designing, implementing a collaborative program. PMID- 2241129 TI - Outpatient hernia repair. The Shouldice technique. PMID- 2241131 TI - Outpatient care needed for AIDS patients. PMID- 2241130 TI - Fibrous bile duct obstructions. Diagnosis, treatment, prognosis. AB - International experiences with operative repair of fibrous strictures indicate that satisfactory results are obtained with 80% to 85% of patients at least three years after the stent is removed. Although opinion regarding the length of time stents should be left in place is not unanimous, stents usually can be removed six months after operation. The mortality rate associated with this operative procedure should be between 1% and 2%. Benign fibrous obstruction of the bile duct occasionally occurs, especially after cholecystectomy. Operative repair, usually with the use of anastomosis of the hepatic duct to the jejunum, gives the best long-term results. Percutaneous transhepatic dilation with the long-term use of a stent to prevent restricture at times is indicated and can be curative. PMID- 2241132 TI - Recommended practices. Surgical hand scrubs. AORN Recommended Practices Coordinating Committee. PMID- 2241133 TI - Ambulatory surgery nurses have unique opportunities to provide patient care. PMID- 2241134 TI - Enhancing trauma skills. PMID- 2241135 TI - Software terms and technology; bits and bytes; disk compatibility; 'boot' disks. PMID- 2241136 TI - Informed, assisted, delegated consent for elderly patients. PMID- 2241137 TI - Applications of the 'captain of the ship' doctrine. PMID- 2241138 TI - Body image and weight preoccupation: a comparison between exercising and non exercising women. AB - Relationships were examined among certain personality characteristics and variables which assess weight, diet, and appearance concerns for two groups of women--those who were avid exercisers (n = 86) and those who exercised only occasionally or not at all (n = 72). Multiple regression analyses indicated that emotional reactivity (measured by the N scale of the Eysenck Personality Inventory) was strongly related to weight preoccupation (measured by three subscales of the Eating Disorder Inventory) in both groups. Body Mass Index (BMI), but not a measure of subjective body shape, also predicted weight preoccupation for the non-exercisers while the opposite relationship was found for exercisers. In this group, subjective body shape and not BMI influenced weight preoccupation. It was also found that greater body dissatisfaction was related to poorer emotional well-being in the exercise group, and these women reported, to a significantly greater degree than non-exercisers, that their physical appearance was important to their self-esteem. It is possible that an excessive preoccupation with diet and body shape leads some women to take up a vigorous exercise program. However, the absence of differences in weight preoccupation between the groups argues against this. A possibility that has seldom been considered in the literature is that dedication to regular exercise fosters a heightened degree of body narcissism and a distorted impression of one's body size. A focus of attention in an exercise program on the relationship between body size and maximal performance may, in susceptible individuals, increase the likelihood of developing an obsessive attitude toward weight control. PMID- 2241139 TI - Opioid effects on intake of sweet solutions depend both on prior drug experience and on prior ingestive experience. AB - Two experiments investigated the effect of opioids on ingestion of sweet solutions in non-deprived rats. Experiment 1 replicated previous work from our laboratory showing virtually complete inhibition of sucrose and saccharin intake during 10 days of daily naloxone treatment. During recovery, prior naloxone experience significantly stimulated sucrose intake but had no effect on saccharin intake. In the absence of naloxone treatment, ingestive experience alone reduced naloxone's typical intake-suppressant effect. These findings suggest that drug experience and ingestive experience may interact to determine the intake suppressant effect of naloxone. Experiment 2 examined the effects of opioid agonists on sucrose ingestion during 10 days of initial drug treatment and 5 days of recovery. A low dose of the kappa agonist U-50,488H significantly stimulated sucrose ingestion during the drug treatment period and this effect persisted for several days after treatment ended. Initial (non-significant) intake suppressant effects of the mu agonist morphine or a high dose of U-50,488H tended to decrease with repeated testing and did not reappear during recovery. These data suggest that in addition to immediate, direct effects on motivation, opioids may affect long-term changes in responsiveness to sweet tastes. PMID- 2241140 TI - Mechanisms of action of the intragastric balloon in obesity: effects on hunger and satiety. AB - We evaluated the effect of a 500-ml intragastric balloon (Ballobes) on some aspects of eating-related behaviour and weight loss on nine massively obese patients. An 800-kcal mixed meal test was performed some days before, 2-3 days and 2 months after the implant of the balloon. A hypocaloric program was started after the second meal test. At hourly intervals, before and after the meal, patients were asked to rate the desire to eat, hunger, satiety and prospective consumption of food. After 2 months, weight loss was 12.0 +/- 5.1 kg. A significant decrease in the balloon diameters was observed, but none completely deflated. During the meal test performed 2-3 days after the implant, subjects rated themselves as significantly less hungry, fuller and desiring to eat less food. These patterns, however, returned to the baseline levels at the meal test performed after 2 months. No relationship was found between weight loss and reduction in the balloon diameters, nor between the latter and the changes in temporal profiles of eating ratings. The effect of a 500-ml balloon on meal related hunger and satiety therefore seems to disappear with time. PMID- 2241141 TI - The effects of d-amphetamine on food intake of humans living in a residential laboratory. AB - Two groups, each consisting of three normal weight, male research volunteers, lived continuously in a residential laboratory for 15 days. All contact with the experimenters was through a networked computer system and subjects' behaviors, including food intake, were continuously recorded. During the first part of the day, subjects remained in their private rooms doing work activities. During the remainder of the day, they had the option to socialize with each other. A wide variety of food items were continuously available. Subjects controlled their own patterns of food intake, and could consume any item, or number of items, at any time during the day. Beverages containing d-amphetamine (10 mg per 70 kg) or placebo were consumed daily at 0930 and 1630 hrs. Amphetamine significantly reduced total daily caloric intake to about 70% of placebo levels. The reduction in intake was a consequence of a decrease in number of eating occasions per day; no changes in mean intake per occasion were observed. Amphetamine produced similar decreases in the daily number of snack and meal items, and in protein, fat, and carbohydrate intake. These results demonstrate that amphetamine has significant effects on human food intake, and the study of human feeding behavior under similar naturalistic conditions should provide important information about the behavioral actions of drugs affecting food intake. PMID- 2241142 TI - Effects of variety on food intake of underweight, normal-weight and overweight women. AB - The food intake of 27 underweight, normal-weight and overweight women was monitored during laboratory luncheon meals of solid food units (SFUs), bite-sized spirals of bread with different sandwich fillings. Simultaneous, but not sequential, presentation of three SFU flavors increased intake compared to presentation of a single flavor in normal-weight and overweight women. Neither variety manipulation enhanced intake in the underweight women, who are more than the other subjects in all conditions. The fact that the foods were so similar probably reduced the effectiveness of the variety manipulations. Overweight and normal-weight subjects had different patterns of intake, but only when eating a single flavor of SFU. Only overweight subjects ate less when three flavors of SFUs were hidden from view in the apparatus used to monitor intake. This procedure prevented subjects from selecting particular flavors of SFUs. Differences in cognitive restraint probably do not explain the differences in the eating behavior of normal-weight and overweight subjects in the present study. Lack of dietary restraint or a high level of hunger may account for the different eating behavior of the underweight subjects compared to the other subjects. PMID- 2241143 TI - Preferences and intake measures of salt and sugar, and their relation to personality traits. AB - The inter-relationship of personality with dietary intake of salt and sugar, and with hedonic responses to saltiness and sweetness, was examined among 62 female and 38 male university students. Thirty-five personality traits were assessed using five standard questionnaires: (1) Sixteen Personality Factor (16PF), (2) Jenkins Activity Survey (JAS), (3) Eysenck Personality Questionnaire (EPQ), (4) Multidimensional Health Locus of Control (MHLC), and (5) Sensation Seeking Scale (SSS). Dietary intakes of salty and of sweet foods were estimated from dietary frequency questionnaires. Hedonic responses to sodium chloride in beef broth and to sucrose in lemonade were measured by category scaling of like/dislike and by ad libitum addition to maximum preference. While subjects with a high salt intake liked saltier broths (p less than 0.05), a similar relationship was not found for sugar intake and sweetness preferences. Hedonic scaling of both saltiness and sweetness was highly related to the ad libitum results. Only a few significant personality effects were observed. The more outgoing individuals liked sweeter lemonade than the more reserved subjects, and subjects who felt they had self control over their health liked lower levels of salt in broth, while those who felt that chance or others controlled their health liked higher levels. Using personality traits as independent variables in step-wise multiple regression analysis accounted for 13% of the variance in the concentrations of salt and sugar, respectively, which received maximum hedonic responses. PMID- 2241144 TI - The effect of high pH upon diphtheria toxin conformation and model membrane association: role of partial unfolding. AB - Penetration of membranes by diphtheria toxin in vivo is at least partially triggered by a low pH-induced conformational change occurring within the lumen of an acidic organelle. In order to gain insight into the nature of this change the behavior of the toxin at high pH was characterized and compared to that previously determined at low pH. We find that near pH 10.5 a major conformational change occurs. This change is accompanied by a marked decrease in fluorescence intensity, a red shift in fluorescence emission maximum, and increased susceptibility of protein fluorescence to acrylamide quenching. Differential scanning calorimetry shows that the high pH conformational change involves a cooperative endothermic unfolding transition. These changes at high pH are very similar to those induced by low pH, supporting the conclusion that the changes at low pH also involve a denaturation-like process. In addition, at high pH the toxin gains the ability to bind to model membranes, again similar to its behavior at low pH. On the basis of these studies we conclude that exposure of hydrophobic sequences due to partial unfolding is one dominating component in inducing hydrophobic behavior at both high and low pH, but that at low pH Asp/Glu protonation also contributes to hydrophobicity. PMID- 2241146 TI - Variations in the activity of glutathione reductase and the cellular glutathione content in relation to sensitivity to methylviologen in Escherichia coli. AB - To study the function of glutathione reductase and glutathione in Escherichia coli the coding sequence of the bacterial glutathione reductase gene (gor gene) was cloned into the vector pBR322, and the gor gene was expressed under the control of the promoter of the tetracycline-resistance gene (tet gene) in different Escherichia coli strains. Cells of the gor-mutant strain SG5 containing the vector pBR322 (SG5:pBR322) had no detectable glutathione reductase activity and a significantly lower total glutathione (GSH + GSSG) content relative to control cells of the strain JM101 (JM101: pBR322). The gor mutant cells were less sensitive to inhibition by methylviologen (as defined by changes in growth) than cells of the strain JM101. Elevated levels of both glutathione reductase activity and the total glutathione content (GSH + GSSG) were found when the gor gene was expressed in cells of the gor-mutant strain SG5 (SG5:pJIK1). Thus the activity of glutathione reductase is essential in order to maintain a high glutathione content. Furthermore, cells of the strain SG5: pJIK1 showed an increased sensitivity to methylviologen compared to cells of the gor mutant containing the vector pBR322 alone without the cloned gor gene insert (SG5:pBR322). In all experiments, the glutathione pool (GSH + GSSG) of bacterial cells was 90% reduced. In methylviologen-sensitive sodB mutant cells lacking iron superoxide dismutase activity (QC773:pBR322) overexpression of the cloned gor gene resulted in an elevated level of glutathione reductase activity which partially protected sodB mutant cells (QC773:pJIK1) against methylviologen toxicity. In sodB mutant cells expressing the gor gene (QC773:pJIK1) protection by glutathione reductase was, however, less effective than protection provided by expression of the iron superoxide dismutase gene (sodB gene) in these mutant cells (QC773:pJIK2). In sodA mutant cells lacking manganese superoxide dismutase activity but expressing the cloned gor gene (QC772:pJIK1) increased cellular glutathione reductase activity did not provide protection against methylviologen. PMID- 2241145 TI - Pattern of accumulation of elastin and the level of mRNA for elastin in aortic tissue of growing chickens. AB - Synthesis and accumulation of elastin in many elastic tissues begins in the last third of fetal development, reaches a maximum shortly after birth, and then declines rapidly. For the aorta of the chick and the pig and the ligamentum nuchae and lung of the sheep, it has been shown that increased levels of elastin production with fetal development are correlated with increased levels of elastin mRNA in the tissue, measured both by cell-free translation and by hybridization to cDNA probes. In this study we examine the relationship between insoluble elastin accumulation and message levels for tropoelastin in aortic tissue of chickens during posthatching development and growth. Whether evaluated by cell free translation or by dot blot hybridization, steady state levels of tropoelastin message increase to a maximum at 2 weeks after hatching, and then fall rapidly with further development and growth. This pattern correlates well with production of insoluble elastin by the aorta, determined either by direct measurements of synthesis or by rate of accumulation of insoluble elastin. The data indicate that the major site of regulation of elastin production is pretranslational throughout the entire period of development and growth of the chicken aorta. PMID- 2241147 TI - Kinetics of purple membrane dark-adaptation in the presence of Triton X-100. AB - The kinetics of purple membrane dark adaptation were studied at pH 5 and 7, in the presence and absence of the nonionic detergent Triton X-100. The effect of both sublytic and lytic surfactant concentrations has been considered. Our results show that: (a) dark adaptation is faster at pH 5 than at pH 7, (b) dark adaptation is slower, and of smaller amplitude, in the presence than in the absence of Triton X-100. The data may be interpreted in terms of a simple first order kinetic model, according to which light-dark adaptation would depend basically on the equilibrium between the 13-cis- and the all-trans-isomers. The experiments also suggest that at pH 5, but not at pH 7, solubilizing surfactant concentrations produce a considerable increase in the velocity of the dark adaptation reaction, perhaps through changes in the microenvironment of a protonable group. PMID- 2241148 TI - The action of the glutathione transferase substrate, 1-chloro-2,4-dinitrobenzene on synaptosomal glutathione content and the release of hydrogen peroxide. AB - We studied the action of the glutathione transferase substrate, 1-chloro-2,4 dinitrobenzene (CDNB) on the synaptosomal production of H2O2. We found that CDNB (30-40 microM) readily depletes the cytosolic glutathione but is almost without effect on the mitochondrial fraction. The depletion of the cytosolic glutathione induced by CDNB affords the detection in the extracellular space of H2O2 produced intrasynaptosomally upon increasing the cytosolic Ca2+ concentration that is otherwise destroyed by glutathione peroxidase. Higher concentrations of CDNB induce a H2O2 production which is not related to the glutathione content. This H2O2 is of mitochondrial origin and requires that NAD be reduced. The primary product of the mitochondrial CD-NB-dependent oxygen reduction is at least in part the superoxide anion. PMID- 2241149 TI - Different types of formaldehyde-oxidizing dehydrogenases in Nocardia species 239: purification and characterization of an NAD-dependent aldehyde dehydrogenase. AB - Three different dehydrogenases able to oxidize formaldehyde were found in the Gram-positive methylotroph, Nocardia sp. 239: an NAD-dependent aldehyde dehydrogenase (NA-ADH), and NAD- and factor-dependent formaldehyde dehydrogenase (FD-FDH), and a dye-linked aldehyde dehydrogenase (DL-ADH). The ratio of the activities observed for the two NAD-linked enzymes varied with growth conditions: batch-wise grown cells had nearly the same activities for both enzymes; in fed batch-wise grown cells (methanol limitation) only FD-FDH was detected. The latter is clearly involved in formaldehyde oxidation, since the enzyme and the factor were found only in methanol-grown cells and the enzyme is specific for formaldehyde. In contrast, the two aldehyde dehydrogenases may have significance for aldehyde dissimilation in general, since both activities could also be demonstrated in ethanol-grown cells (but not in glucose-grown cells) and higher aldehydes are even better substrates than formaldehyde. NA-ADH was purified to homogeneity. The enzyme seems to be a homotetramer since it showed a relative molecular mass of 200,000 and the denaturated form of 55,000. Other characteristics are as follows: the enzyme showed substrate inhibition for the aldehydes tested; optimal activity was found at pH 9.2; the reverse reaction was not observed; the enzyme was specific for NAD; GSH, K+, or NH4+ addition did not stimulate formaldehyde oxidation; the order of NAD and substrate addition to the enzyme was not important; several compounds able to block SH groups were inhibitory. Comparison with NAD-linked aldehyde dehydrogenases from Gram-negative bacteria showed that the Nocardia enzyme is distinct from the enzyme of Pseudomonas putida (EC 1.2.1.46) and of Hyphomicrobium X. PMID- 2241150 TI - Increased vitamin E content in the lung after ozone exposure: a possible mobilization in response to oxidative stress. AB - Vitamin E (vE) is a biological free radical scavenger capable of providing antioxidant protection depending upon its tissue content. In previous studies, we observed that vE increased significantly in rat lungs after oxidant exposure, and we postulated that vE may be mobilized to the lung from other body sites under oxidative stress. To test this hypothesis, we fed Long-Evans rats either a vE supplemented or a vE-deficient diet, injected them intraperitoneally with 14C labeled vE, and then exposed half of each group to 0.5 ppm ozone (O3) for 5 days. After exposure, we determined vE content and label retention in lungs, liver, kidney, heart, brain, plasma, and white adipose tissue. Tissue vE content of all tissues generally reflected the dietary level, but labeled vE retention in all tissues was inversely related to tissue content, possibly reflecting a saturation of existing vE receptor sites in supplemented rats. Following O3 exposure, lung vE content increased significantly in supplemented rats and decreased in deficient rats, but the decrease was not statistically significant, and vE content remained unchanged in all other tissues of both dietary groups. Retention of 14C-labeled vE increased in all tissues of O3-exposed rats of both dietary groups, except in vE-deficient adipose tissue and vE-supplemented brain, where it decreased, and plasma, where it did not change. The marked increases in lung vE content and labeled vE retention of O3-exposed vE-supplemented rats support our hypothesis that vE may be mobilized to the lung in response to oxidative stress, providing that the vitamin is sufficiently available in other body sites. PMID- 2241151 TI - Three-step purification method and characterization of the bovine brain 90-kDa heat shock protein. AB - A protein that cross-reacted with antibody against the 90-kDa heat shock protein (HSP90) of a mouse lymphoma cell line was purified from bovine brain by three steps. Fifty milligrams of the 90-kDa protein was recovered from 350 g of the brain cortex. The sedimentation coefficient and Stokes radius of the purified protein were 6.0 s and 6.7 nm, respectively. The molecular weight was calculated to be 170,000. The molecule was composed of two identical 90-kDa subunits. A partial amino acid sequence (23 residues) of this protein was homologous (96%) to human HSP90 (the sequence of 174-196). These facts led to the identification of the 90-kDa brain protein with HSP90. In bovine tissues, the brain contained this protein at a remarkably high concentration. The brain HSP90 was separable from glucocorticoid receptor by heparin-agarose and DNA-cellulose columns. It is concluded that HSP90 is present in brain cytosol and mostly as free molecules. Immunohistochemical studies showed that the protein was localized in nerve excitable cells. It was not found in nuclei but in cytosol. PMID- 2241152 TI - Thermodynamic nonideality as a probe of reversible protein unfolding effected by variations in pH and temperature: studies of ribonuclease. AB - Thermodynamic nonideality arising from the space-filling effect of added sucrose is employed to confirm that the reversible unfolding of ribonuclease A effected by acid may be described as an equilibrium between native and unfolded states of the enzyme. However, the extent of the volume change is far too small for the larger isomer to be the fully expanded state, a result signifying that the acid mediated unfolding of ribonuclease does not conform with the two-state equilibrium model of protein denaturation. Although the thermal denaturation of ribonuclease A is characterized by a larger increase in volume, quantitative reappraisal of published results on the effects of glycerol on this transition at pH 2.8 (Gekko, K., and Timasheff, S. N., 1981 Biochemistry 20, 4677-4686) leads to an estimated volume increase that is much smaller than that inferred from hydrodynamic studies--a disparity attributed to the dual actions of glycerol as a space-filling solute and as a ligand that binds preferentially to the thermally unfolded form of the enzyme. Even in this unfavorable circumstance the fact that glycerol exerts a net excluded volume effect at least confirms that the thermal unfolding of ribonuclease A is an equilibrium transition between two discrete states. The strengths and limitations of using thermodynamic nonideality as a probe of the two-state equilibrium model of protein denaturation are discussed in the light of these findings. PMID- 2241153 TI - Presence of individual enzymes of cholesterol biosynthesis in rat liver peroxisomes. AB - Cholesterol biosynthesis by isolated rat liver peroxisomes was examined. Labeling of cholesterol from [3H]-mevalonate in the presence of peroxisomes required the addition of cytosol, since peroxisomes, like microsomes, apparently possess only those enzymes of cholesterol biosynthesis subsequent to the steps involving farnesyl-PP. Under the conditions employed the amounts of 4,4-dimethyl and desmethyl sterols generated by peroxisomes were equal to or exceeded those produced by the microsomes. In addition, marker enzyme analysis demonstrated minimal microsomal contamination in the peroxisomal fraction. The metabolite patterns observed by HPLC after incubation of these two fractions with [3H]mevalonate were different. Dihydrolanosterol oxidase, steroid-14-reductase, steroid-8-isomerase, and steroid-3-ketoreductase activities were present in peroxisomes. Separation of peroxisomes into membranes and contents revealed that all the synthesizing activities are associated with the membrane fraction. 7 alpha-Hydroxylase, which catalyzes the first step in the biosynthesis of bile acids, was also present in peroxisomes, but it remains to be clarified to what extent peroxisomal cholesterol is a substrate for bile acid synthesis. PMID- 2241155 TI - Studies on the interaction of a thiol-dependent hydrogen peroxide scavenging enzyme and phenylalanine hydroxylase. AB - Rat liver phenylalanine hydroxylase is irreversibly inactivated by a H2O2 dependent process. Since H2O2 can be produced by autooxidation of the tetrahydropterin cofactor required for the hydroxylation reaction, in vitro assays are usually carried out in the presence of added catalase. On the basis of a dithiothreitol-dependent protecting assay of phenylalanine hydroxylase, carried out in the absence of catalase, we have isolated an enzyme fraction from neonatal rat livers which has similar properties to the known enzyme, glutathione peroxidase. The developmental time course for phenylalanine hydroxylase in rats has been reported to follow two different patterns. Using the dithiothreitol assay, McGee et al. (1972, Biochem. J. 127, 669-674) have found that newborn rats have low phenylalanine hydroxylase activity which increases to adult levels over several months. On the other hand, using catalase-supplemented assays, others have found that newborn rats have nearly adult levels of phenylalanine hydroxylase activity. The protective effect of glutathione peroxidase on phenylalanine hydroxylase suggests that the developmental time course found by McGee et al. may represent the slow developmental time course previously found for glutathione peroxidase. In addition, feeding rats a selenium-deficient diet, which reduces the hepatic activity of the selenium-containing glutathione peroxidase, results in a concomitant irreversible loss of phenylalanine hydroxylase activity, suggesting that glutathione peroxidase may play a vital role in protecting phenylalanine hydroxylase in vivo from peroxide inactivation. PMID- 2241154 TI - Heme oxygenase-2 mRNA: developmental expression in the rat liver and response to cobalt chloride. AB - We have previously identified two isozymes of heme oxygenase, HO-1 and HO-2, in the rat liver exhibiting vastly different molecular biochemical properties, including their responses to various chemical inducers. In the present study of the livers of fetal and newborn rats (-1 day to 21 days) we observed marked differences in the developmental pattern of expression of the transcripts for the two forms of heme oxygenase. In addition, the transcripts for HO-1 and HO-2 vary in their number and response to treatment with cobalt chloride. Specifically, using a full length cDNA probe for HO-2, we observed the 1.3-kb mRNA previously shown to encode HO-2 in the testis, as well as a second less abundant transcript of 1.9 kb. An HO-1 cDNA probe detected only the anticipated single transcript of 1.8 kb. The abundance of each HO-2 homologous transcript was unaffected by cobalt chloride treatment (4 or 24 h) in newborn (7 days old) and adult rats. The 1.8-kb HO-1 mRNA, however, was markedly increased in abundance in both age groups by this treatment. The 1.3-kb HO-2 mRNA level nearly doubled after parturition, but remained essentially unchanged during the first 2 weeks of life, and only modestly increased by age 21 days. At all stages of development, the relative abundance of the 1.3- and 1.9-kb transcripts remained unchanged. In the case of 1.8-kb HO-1 mRNA, the level of mRNA was relatively constant during the first week of life, but was substantially reduced by age 14 days, and was further decreased by age 21 days and in the adult animals. In adult rats, the abundance of the 1.3 kb HO-2 mRNA did not markedly increase over that detected in the course of the early postparturition developmental period. The data suggest that the abundance of the two HO-2 homologous transcripts is not readily subject to regulation by chemicals at any stage of development. The expression of HO-1, on the other hand, is subject to such regulation throughout life, and its high transcript abundance in newborn rats may well reflect availability of an endogenous inducer. PMID- 2241156 TI - Hydroperoxidase I catalyzes peroxidative activation of 3,3'-dichlorobenzidine to a mutagen in Salmonella typhimurium. AB - Dichlorobenzidine can be peroxidatively activated in Salmonella typhimurium Ames tester strains. Mutagenicity is observed when an S. typhimurium strain which is sensitive to frame-shift mutagens is incubated with dichlorobenzidine and hydrogen peroxide. In this paper, we show that the bacterial enzyme, hydroperoxidase I, is responsible for much of this activation. We constructed isogenic tester strains which lack hydroperoxidase I or II, due to Tn10 insertions in the structural genes encoding these proteins. Hydrogen peroxide dependent mutagenicity of dichlorobenzidine was measured in each strain. A tester strain lacking hydroperoxidase I activity was much less sensitive than was the parent strain. When hydroperoxidase I activity was restored in this strain, via a plasmid-borne copy of the gene encoding the Escherichia coli protein, sensitivity to peroxide-dependent dichlorobenzidine mutagenicity was enhanced. PMID- 2241157 TI - Characterization of the 46,000-dalton subunit of eIF-4F. AB - Three protein synthesis initiation factors, eukaryotic initiation factor (eIF) 4A, -4B, and -4F are required for the ATP-dependent binding of mRNA to the ribosome. To extend the characterization of the eIF-4A-like subunit of eIF-4F, a cDNA clone encoding eIF-4A has been isolated from a rabbit liver cDNA library and sequenced. The clone is almost full length for the coding region and complete for the 3' noncoding region. The sequence of the rabbit cDNA has been compared to the sequence of the two similar, but not identical, genes and cDNAs encoding mouse eIF-4A (termed eIF-4AI and eIF-4AII). The rabbit cDNA sequence is very similar to the mouse eIF-4AI genomic and liver cDNA sequence with 100% identity at the amino acid level and 90% identity at the nucleotide level within the protein coding region; however, there is very little similarity in the 3' noncoding region. Amino acid sequencing of purified rabbit reticulocyte eIF-4A protein indicates that it is eIF-4AI (encoded by the eIF-4AI gene and cDNA) and none of the amino acid residues sequenced are in disagreement with those predicted from the mouse liver or rabbit liver cDNA sequences. Subsequently, we have analyzed the p46 subunit of eIF-4F, a three subunit protein whose molecular weights have been estimated by sodium dodecyl sulfate gel electrophoresis to be 220,000, 46,000 and 24,000. The p46 subunit has physical properties similar to eIF-4A. This subunit was isolated from rabbit reticulocyte eIF-4F and sequenced chemically. Our results indicate that this peptide is a mixture of eIF-4AI and eIF-4AII in an approximate ratio of 4 to 1, respectively. No eIF-4AII was observed in our rabbit reticulocyte eIF-4A preparation. Therefore we have concluded that either the eIF 4AI and the eIF-4AII proteins were resolved from each other in the purification of rabbit reticulocyte eIF-4A or that eIF-4AII preferentially associates with the p220 and p24 subunits of eIF-4F. Evidence favoring the latter possibility is discussed. PMID- 2241158 TI - Role of heme in phenobarbital induction of cytochromes P450 and 5-aminolevulinate synthase in cultured rat hepatocytes maintained on an extracellular matrix. AB - When hepatocytes are cultured on matrigel, a reconstituted basement membrane matrix, mRNAs for cytochrome P450 class IIB1/2 and class III genes can be induced by treatment with phenobarbital. We took advantage of this new system to critically evaluate the role of heme as a regulator of these cytochromes P450 and of 5-aminolevulinate synthase (ALA-S), the rate-limiting enzyme in heme biosynthesis. Phenobarbital treatment of rat cultures increased the total amount of cytochrome P450, activities catalyzed by IIB1/2 (benzyloxy- and pentoxyresorufin O-dealkylases) and ALA-S activity, and ALA-S mRNA. Treatments with phenobarbital combined with succinyl acetone, an inhibitor of heme biosynthesis at the step of 5-aminolevulinate dehydrase, blocked the induction of the proteins for cytochrome P450IIB1/2 and cytochrome P450IIIAI, as indicated by spectral, immunological, and enzymatic assays. However, at the same time, succinyl acetone cotreatment failed to inhibit the induction of the mRNAs for cytochrome P450IIB1/2 and cytochrome P450IIIA. Lack of effect on the cytochrome P450 mRNAs was selective inasmuch as treatment with phenobarbital combined with succinyl acetone synergistically increased both ALA-S activity and ALA-S mRNA, presumably by blocking formation of heme, the feedback repressor of ALA-S. Indeed, the increase in ALA-S mRNA caused by the combined treatment was abolished by adding heme itself to the cultures. In contrast to earlier concepts, we conclude that in the intact hepatocyte, phenobarbital-induced cytochrome P450 induction is independent of changes in heme synthesis. PMID- 2241159 TI - Chemical modification of chalcone isomerase by diethyl pyrocarbonate: histidine residues are not essential for catalysis. AB - Chalcone isomerase form soybean is inactivated by treatment with diethyl pyrocarbonate (DEP). The competitive inhibitor 4',4-dihydroxychalcone provides kinetic protection against inactivation by DEP with a binding constant at the site of protection in agreement with its binding constant at the active site. Very high concentrations of the competitive inhibitors 4',4-dihydroxychalcone or morin hydrate offer a 10- to 40-fold maximal protection, suggesting a second slower mechanism for inactivation which cannot be prevented by blockage of the active site. Blockage of the only cysteine residue in chalcone isomerase with p mercuribenzoate does not affect the rate constant for DEP-dependent inactivation and indicates that the modification of the cysteine residue is not responsible for the activity loss observed in the presence of DEP. Treatment of inactivated enzyme with hydroxylamine does not restore catalytic activity, indicating that the modification of histidine or tyrosine residues is not responsible for the activity loss. All five histidines of chalcone isomerase are modified by DEP at pH 5.7 and ionic strength 1.0 M. The rate constant for the modification of the histidine residues of chalcone isomerase is close to that for the reaction of N acetyl histidine with DEP, indicating that the histidine residues are quite accessible to the modifying reagent. The rate of histidine modification is the same in native enzyme, in urea-denatured enzyme, and in the presence of a competitive inhibitor. In the presence of the competitive inhibitor morin hydrate, all of the histidine residues of chalcone isomerase can be modified without significant loss in catalytic activity. These results demonstrate that the histidine residues of chalcone isomerase are not essential for catalysis and therefore cannot function as nucleophilic catalysts as previously proposed. PMID- 2241160 TI - Aspartate aminotransferase from Eleusine coracana, a C4 plant: purification, characterization, and preparation of antibody. AB - Aspartate aminotransferase (AspAT) isozymes from Eleusine coracana (an NAD-malic enzyme type C4 plant) were examined. Three groups of isoenzymes were identified (AspAT-1, AspAT-2, and AspAT-3). AspAT-1 (localized in the mesophyll cells) and AspAT-3 (localized in the bundle sheath cells), both of which are considered to function in the C4 acid pathway, were purified and their kinetic and physical properties studied. Both isoenzymes had a molecular mass of 80 kDa and were shown to consist of two identical 40-kDa monomers. Except for the higher affinity for aspartate and the lower activity for the forward direction (Asp----OAA) at lower pH exhibited by AspAT-3 compared with AspAT-1, the isozymes had similar kinetic properties. However they had quite different isoelectric points. Polyclonal antibodies raised against AspAT-3 preferentially cross-reacted with AspAT-3 but did show some cross-reactivity with AspAT-1. PMID- 2241161 TI - Substitution of Gly-96 to Ala in the 5-enolpyruvylshikimate-3-phosphate synthase of Klebsiella pneumoniae results in a greatly reduced affinity for the herbicide glyphosate. AB - The aroA gene of Klebsiella pneumoniae encoding the shikimate pathway enzyme 5 enolpyruvylshikimate 3-phosphate (EPSP) synthase, which is the target of the herbicide glyphosate, was cloned and sequenced from both the wild-type and the glyphosate-resistant mutant K. pneumoniae K1, which possesses a glyphosate insensitive EPSP synthase. Both genes were expressed in Escherichia coli and were capable of complementing an auxotrophic aroA mutation. The transformed cells showed increased tolerance to glyphosate due to the overproduction of either the mutant or the wild type EPSP synthase. Nucleotide sequence analysis of the K. pneumoniae aroA gene indicated a protein-coding region of 427 amino acids with a derived Mr for the EPSP synthase of 45,976. Comparison of the two aroA alleles showed a single base change resulting in a substitution of Gly-96 to Ala in the deduced amino acid sequence. By comparison with other known EPSP synthase sequences the mutation was shown to be located in a highly conserved region, indicating that this region is essential for the binding of the herbicide glyphosate. PMID- 2241162 TI - Fluorescence studies with malate dehydrogenase from Bradyrhizobium japonicum 3I1B 143 bacteroids: a two-tryptophan containing protein. AB - A number of fluorescence studies, both of trp residues and bound NADH, have been reported for porcine malate dehydrogenase (MDH). The large number of trp residues (six) complicates the interpretation of some studies. To circumvent this we have performed studies with a two-tryptophan (per subunit) MDH from Bradyrhizobium japonicum 3I1B-143 bacteroids. We have performed phase/modulation fluorescence lifetime measurements, as a function of temperature and added quencher KI, in order to resolved the 1.2-ns (blue) and 6.5-ns (red) contributions from the two classes of trp residues. Anisotropy decay studies have also been performed. The binding of NADH dynamically quenches the fluorescence of both trp residues, but, unlike mammalian cytoplasmic and mitochondrial MDH, there is not a large enhancement in fluorescence of bound NADH upon forming a ternary complex with either tartronic acid or D-malate. PMID- 2241163 TI - Isoforms of chicken triosephosphate isomerase are due to specific oxidation of cysteine126. AB - The electrophoretic isoforms of mammalian triosephosphate isomerase (TPI; EC 5.3.1.1) are due to deamidation at two Asn-Gly sites (Asn15 and Asn71). Deamidation of these two asparagines in the subunit-subunit interface of the isologous dimer appears to destabilize the dimer and initiate degradation of the protein. Chicken TPI contains a lysine substitution for Asn71, thus precluding this deamidation site. Nevertheless, the chicken enzyme exhibits three electrophoretic isoforms. This multiplicity is not the result of deamidation of the remaining Asn15 site, but due to a specific site which is highly susceptible to oxidation. The three isoforms of chicken TPI can be reduced to a single form in the presence of high concentrations of reducing agents (e.g., greater than 15 mM dithiothreitol or greater than 50 mM 2-mercaptoethanol) and are also generated when oxidizing agents, such as oxidized glutathione, are present. The oxidized isoforms exhibit lowered catalytic activity and are more susceptible to denaturation and proteolytic degradation than the native enzyme. Structural analysis of the isoforms by chemical cleavage at the cysteine peptide bonds with 2-nitro-5-thiocyanobenzoic acid and subsequently at the methionines with CNBr followed by peptide sequencing reveals that Cys126 is the site of the modification. Since the oxidized isoforms of chicken TPI accumulate in vivo during aging analogous to the deamidated isoforms from mammals, it appears that TPI is the first example of a protein which has evolved two specific types of weak links which may initiate turnover of the protein. PMID- 2241164 TI - Isolation and characterization of human glucose-6-phosphate isomerase isoforms containing two different size subunits. AB - Previously undetected isoforms of human glucose-6-phosphate isomerase (GPI) have been isolated utilizing substrate-induced elution of the enzyme from spherical cross-linked phosphocellulose as an affinity ligand and subjected to a series of physical and chemical studies. The two major isoforms (1, 48%, pI 9.13; 2, 36%, pI 9.00) are homodimers of subunits of 63.2 kDa (Type-A) and are charge isomers, probably representing deamidation of specific Asn-Gly sequences as in other species. Isoform 3 (13%, pI 8.84) is a heterodimer composed of the Type-A subunit and a previously unreported larger subunit of 69.8 kDa (Type-B). Isoform 4 (3%, pI 8.62) is a BB-homodimer. Structural differences in the two types of subunits are also apparent from CNBr fragmentation patterns. Carbohydrate analyses show that, even though potential N- and O-linked glycosylation sites exist, the isoforms are not due to glycosylation. Recently recognized sequence similarities between GPI and the neurotropic lymphokine, neuroleukin (NLK) suggest that GPI and NLK are either derived from the same gene or represent modifications of the same protein. The possibility of NLK-GPI dimers exists, but the new isoforms identified in this study do not appear to represent hybrids of GPI subunits with mature NLK. PMID- 2241165 TI - Expression of mammalian renal transporters in Xenopus laevis oocytes. AB - We have injected mRNA from rabbit renal cortex into Xenopus oocytes and demonstrated the expression of renal carriers for Na(+)-independent transport of L-phenylalanine and L-lysine and Na(+)-dependent transport of L-alanine and succinate. Maximal expression of renal amino acid transporters occurred 6-8 days following mRNA injection. The proteins responsible for transport of these four substrates were translated from mRNAs which are between 1.5 and 3.0 kb. This information serves as a starting point for expression cloning of these transport proteins. PMID- 2241166 TI - Diversity in responses from endogenous and expressed mammalian receptors which cause chloride ion efflux from ovarian follicles of Xenopus laevis. AB - Inositol phosphates are produced in ovarian follicles of Xenopus laevis on activation of endogenous acetylcholine receptors, which also stimulates Ca2+ release and efflux of Cl- ions detected electrophysiologically. Inositol phosphates were not detectable on activation of endogenous angiotensin II receptors which did, however, stimulate both a dose-dependent Ca2+ efflux and a depolarizing current very similar in maximum size and other characteristics to those caused by acetylcholine action. In contrast, activation of exogenous receptors for angiotensin II expressed by microinjected mRNA extracted from bovine adrenal did form measurable inositol phosphates. Also, the endogenous electrophysiological responses to angiotensin II and acetylcholine desensitize homologously but fail to cross-desensitize (Lacy, McIntosh, and McIntosh, 1989, Biochem. Biophys. Res. Commun, 159, 658-663). It appears that endogenous ovarian angiotensin II receptors in Xenopus activate a different transduction mechanism from endogenous acetylcholine receptors and expressed mammalian adrenal angiotensin II receptors and/or may be sited in the electrically connected follicular cells rather than in the oocyte itself. PMID- 2241167 TI - Human immunodeficiency viral protease is catalytically active as a fusion protein: characterization of the fusion and native enzymes produced in Escherichia coli. AB - Processing of the gag and pol gene precursor proteins of retroviruses is essential for the production of mature infectious virions. The processing is directed by a viral protease that itself is part of these precursors and is presumed to cleave itself autocatalytically. To facilitate study of this process, the protease was produced as a fusion protein in Escherichia coli. In this construct, the 10,793-Da protease was preceeded by two copies of a modified IgG binding domain derived from protein A. The IgG binding domain was linked to the protease by an Asp-Pro peptide bond which could not be cleaved by the viral protease. A dimer of the 25,400-Da fusion protein was catalytically active, specifically cleaving a substrate peptide at the correct Tyr-Pro bond. Thus, the fusion protein could serve as a model of the viral gag-pol polyprotein. The finding that the fusion protein was catalytically active supports the suggestion that a gag-pol dimer can initiate a proteolytic cascade after budding of the immature virus. The fusion protein also provided a source of authentic protease. The protease was released from the fusion construct by incubation with formic acid, cleaving the Asp-Pro linkage which had been inserted between the IgG binding domain and the protease. PMID- 2241168 TI - New tandem-repeating peptide structures in polysialoglycoproteins from the unfertilized eggs of kokanee salmon. AB - New polysialoglycoproteins, designated PSGP(On), were isolated from the fertilized and unfertilized eggs of the kokanee salmon, Oncorhynchus nerka adonis. The polysialylglycan chains consisting of alpha-2,8-linked O-acetylated poly(N-glycolylneuraminyl) chains have recently been characterized. We have now determined the complete amino acid sequence of the tandem-repeating units of PSGP(On) from the unfertilized eggs of kokanee salmon and found that the following two distinct forms are present in PSGP(On) in almost identical amounts: [formula: see text] and [formula: see text] where * denotes the O-glycosylation site and mean value of m, n = about 20. Upon fertilization these high-molecular weight forms of PSGP(On) were proteolytically cleaved to the corresponding repeating units, low-molecular-weight PSGP(On), by the action of a specific protease (PSGPase) at the position two residues set C-terminally to the Pro residue and N-terminally to the Asp residue, i.e. -Pro-Ser-Xaa-Asp-: [formula: see text] and [formula: see text]. PMID- 2241169 TI - Effect of ligand-induced conformational changes on the reactivity of specific sulfhydryl residues in rat brain hexokinase. AB - Rat brain hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) contains 21 cysteine residues. On the basis of the amino acid sequence of the enzyme, these are predicted to be distributed among 14 peptides produced by tryptic digestion. Ten of these peptides, containing cysteine residues derivatized by reaction with the specific sulfhydryl reagent 2-bromoacetamido-4-nitrophenol have been identified in HPLC peptide maps; the four missing peptides are predicted to be relatively large and hydrophobic in character, properties that may have prevented their detection under the present conditions. The sequences encompassed by the 10 identified peptides include 12 of the 21 cysteine residues in the enzyme. The relative reactivity of these sulfhydryl groups with 2-bromoacetamido-4 nitrophenol has been assessed, and is in general accord with what might be predicted on the basis of their accessibility in the previously proposed structure for this enzyme. The effect of various ligands on reactivity of identified sulfhydryl groups has been determined; unique patterns of altered reactivity, resulting from ligand-induced conformational changes, have been observed. Biphasic effects were observed with increasing concentrations of either glucose 6-phosphate (Glc-6-P) or Pi. In both cases, decreased reactivity of sulfhydryls in the N-terminal half of the molecule was observed at low concentrations of the ligand, while further increase in ligand concentration resulted in decreased reactivity of sulfhydryl groups in the C-terminal half. In contrast, sulfhydryls in both N- and C-terminal halves were protected concomitantly by increasing concentrations of Glc. These results are consistent with previous studies that indicated (a) the existence of two sites for binding of Glc-6-P or Pi, a high affinity site in the N-terminal half and a site with lower affinity in the C-terminal half of the brain hexokinase molecule, and (b) binding of Glc to a single site located in the C-terminal half but evoking conformational effects throughout the molecule; the glucose analog, N acetylglucosamine, previously shown to have more limited effects on conformation, affected reactivity of sulfhydryl groups only in the C-terminal half of the molecule. As reflected by effects on reactivity of sulfhydryl groups, conformational changes induced by binding of nucleotides depends markedly on the specific nature of the purine or pyrimidine base as well as the length and chelation status of the polyphosphate side chain. These results focus attention on specific regions of the molecule (the immediate environment of the sulfhydryl groups) that are affected by the binding of these ligands. PMID- 2241170 TI - Regulation of intestinal calbindin-D28K gene expression: a solution hybridization study. AB - A solution hybridization assay employing specific synthetic oligodeoxynucleotide probes was developed to study the regulation of intestinal calbindin-D28K mRNA. The technique is rapid and quantitative and eliminates the need for sample transfer, blotting, autoradiography, and densitometry. Following validation of the assay, chick intestinal calbindin-D and calbindin-D mRNA levels were compared under conditions known to stimulate intestinal calcium (Ca) transport. Both the protein and its mRNA were undetectable in 25-day-old vitamin D-deficient chicks. Following acute administration of vitamin D3, calbindin-D mRNA levels increased somewhat more rapidly than calbindin-D protein, but overall, the correlation was excellent. Chicks fed a nutritionally adequate diet for 14 days and then changed to a low Ca (0.1%) diet responded with increased calbindin-D and calbindin-D mRNA levels. Again the correlation was excellent over the ensuing 14-day experimental period. The combined effects of vitamin D repletion and dietary Ca status were also investigated with respect to calbindin D and its mRNA. Fourteen-day-old vitamin D-deficient chicks were changed to diets containing vitamin D and either adequate (1.2%) or low (0.3%) in Ca. The intestinal responses were measured at intervals up to 14 days. In the normal Ca situation, there were initial increases in both calbindin mRNA levels, which peaked at between 4 and 7 days, and calbindin protein levels, which peaked at 7 days. Both values subsequently declined during the remaining 7 days of the experimental period. In the low Ca situation, there were similar increases in calbindin mRNA and protein levels through 4 and 7 days respectively, but these levels remained high for the remainder of the 14-day experimental period. The present results demonstrate that intestinal tissue levels of calbindin D and its mRNA respond similarly to vitamin D repletion and dietary Ca restriction as well as the combination of these stimuli. There is no evidence to support significant post-transcriptional regulation of calbindin-D by Ca. PMID- 2241171 TI - Site-specific oxidation of angiotensin I by copper(II) and L-ascorbate: conversion of histidine residues to 2-imidazolones. AB - The reaction of a histidine-containing peptide (angiotensin I) with copper (II)/ascorbate under physiological conditions has been studied chemically. In the presence of a catalytic amount of copper(II) ion, ascorbate mediated the oxidative damage to the peptide via selective loss of the histidine residue. Furthermore, the reaction of copper(II)/ascorbate with the peptide gave two products (AGT-1 and AGT-2) selectively. From amino acid analysis of the modified peptides, it was found that either of the two histidine residues within the native peptide was modified. Amino-terminal sequence analysis indicated that AGT 1 and AGT-2 were modified at the His9 and the His6, respectively. In addition, the data of FAB-MS and 1H NMR suggested that the unknown residues (modified histidine) within AGT-1 and AGT-2 should have the 2-imidazolone structure. In order to confirm the 2-imidazolone residue in both modified peptides, they were hydrolyzed and analyzed by reverse-phase HPLC. The result demonstrated that the acid hydrolysis of modified peptides gave a product which was identical to authentic 2-imidazolone residue. Consequently, it was confirmed that the reaction of Cu(II)/ascorbate occurs specifically at the C-2 position of the imidazole ring of the histidine residue within a peptide. PMID- 2241172 TI - Glycosphingolipid-binding specificity of the mannose-binding protein from human sera. AB - Mannose-binding protein was purified from human serum to apparent homogeneity by affinity chromatography on mannose-Sepharose, followed by affinity chromatography on underivatized Sepharose. Approximately 0.4 mg protein was obtained from 1 liter serum. The glycosphingolipid-binding specificity of the purified protein was examined by chromatogram overlay and solid phase assays. It binds with high affinity to Lc-3Cer (GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1ceramide) and n Lc5Cer (GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1 1ceramide). It does not bind to many other glycosphingolipids without terminal N acetylglucosamine residues that were tested. Thus, these data suggest that N acetylglucosamine-terminated glycosphingolipids may serve as cell-surface attachment sites for mannose-binding protein in vivo. In addition, the binding specificity of the protein can be used as a sensitive probe for determining the levels of Lc3Cer and nLc5Cer in tissues, as it exhibits half-maximal binding to about 10 pmol of these lipids in solid phase assays, and detects less than 20 pmol of Lc3Cer in chromatogram overlay assays. This technique was utilized to demonstrate that one sample of chronic myeloid leukemia cells contains both Lc3Cer and nLc5Cer. PMID- 2241174 TI - Tributyltin stimulates apoptosis in rat thymocytes. AB - Treatment of rat thymocytes with micromolar concentrations of tributyltin caused a rapid increase in the cytosolic free Ca2+ concentration that was inhibited by Ni2+, which blocks Ca2+ influx through membrane channels. The elevation of cytosolic Ca2+ was associated with extensive DNA fragmentation, which was prevented by pretreatment of the cells with either of the intracellular Ca2+ chelators quin-2 or 1,2-bis(2-amino-phenoxy)ethane-N',N',N',N',-tetraacetic acid. Loss of thymocyte viability, which followed DNA fragmentation, was also prevented by the two Ca2+ chelators or by removing extracellular Ca2+ with ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid. The pattern of DNA fragmentation was characteristic of that produced by agents which activate a Ca2(+)- and Mg2(+) dependent endogenous endonuclease during apoptosis or programmed cell death. Additional studies showed that other organotin compounds, including trimethyltin, triphenyltin, and dibutyltin had minimal effects on cytosolic Ca2+, DNA fragmentation, and cell viability. These results are consistent with a greater susceptibility of thymocytes to tributyltin and provide a basis for understanding its selective immunotoxicity in vivo. PMID- 2241173 TI - Fibronectin and proteoglycan synthesis in long term cultures of cartilage explants in Ham's F12 supplemented with insulin and calcium: effects of the addition of TGF-beta. AB - Canine cartilage explants were maintained in a basal medium supplemented with a commercially available supplement (ITSCR+) which includes insulin for up to 12 days in culture. During this time it was found that proteoglycan synthesis, as measured by 35SO4 incorporation into high molecular weight proteoglycans, was maintained at levels comparable to those at Day O. This is in substantial agreement with the results of McQuillan et al. (1) for bovine cartilage explants. Since the basal medium which we used, Ham's F12, is low in calcium, we found that supplementation with additional calcium also was needed for maintenance of proteoglycan synthesis. This defined medium was not adequate to prevent a decrease in fibronectin, total protein, and collagen synthesis relative to Day O levels. The addition of transforming growth factor-beta (TGF-beta) at 2 and 10 ng/ml to the defined medium not only prevented the decline in fibronectin synthesis but progressively increased the rate of fibronectin synthesis until the Day O levels were exceeded by an average of fourfold. This TGF-beta-induced increase in fibronectin synthesis was contrasted with the increase in fibronectin synthesis previously reported for degenerated cartilage of osteoarthritic joints (2,3), and possible implications for understanding the disease were discussed. PMID- 2241175 TI - Novel forms of ferredoxin and ferredoxin-NADP reductase from spinach roots. AB - Ferredoxin and the enzyme catalyzing its reduction by NADPH, ferredoxin-NADP reductase (ferredoxin-NADP+ oxidoreductase or FNR), were found to be present in roots of spinach (Spinacia oleracea). Localization experiments with endosperm of germinating castor beans (Ricinus communis), a classical nonphotosynthetic tissue for cell fractionation studies, confirmed that ferredoxin and FNR are localized in the plastid fraction. Both proteins were purified from spinach roots and found to resemble their leaf counterparts in activity, spectral properties, and complex formation, but to differ in amino acid composition and amino terminal sequence. The results indicate that the primary structures of the FNR and ferredoxin of spinach roots differ from that of the corresponding leaf proteins. Together with earlier findings, the present results provide evidence that nonphotosynthetic plastids, including those of roots, are capable of reducing ferredoxin with heterotrophically generated NADPH. PMID- 2241177 TI - The kinetic mechanisms of the bifunctional enzyme aspartokinase-homoserine dehydrogenase I from Escherichia coli. AB - The kinetic mechanisms of the reactions catalyzed by the two catalytic domains of aspartokinase-homoserine dehydrogenase I from Escherichia coli have been determined. Initial velocity, product inhibition, and dead-end inhibition studies of homoserine dehydrogenase are consistent with an ordered addition of NADPH and aspartate beta-semialdehyde followed by an ordered release of homoserine and NADP+. Aspartokinase I catalyzes the phosphorylation of a number of L-aspartic acid analogues and, moreover, can utilize MgdATP as a phosphoryl donor. Because of this broad substrate specificity, alternative substrate diagnostics was used to probe the kinetic mechanism of this enzyme. The kinetic patterns showed two sets of intersecting lines that are indicative of a random mechanism. Incorporation of these results with the data obtained from initial velocity, product inhibition, and dead-end inhibition studies at pH 8.0 are consistent with a random addition of L-aspartic acid and MgATP and an ordered release of MgADP and beta-aspartyl phosphate. PMID- 2241176 TI - Hemin-promoted peroxidation of red cell cytoskeletal proteins. AB - Hemin-induced crosslinking of the erythrocyte membrane proteins was analyzed at three levels: (i) whole membranes, (ii) integrated or dissociated cytoskeletons, and (iii) isolated forms of the three main cytoskeletal proteins, spectrin, actin, and protein 4.1. Addition of H2O2 and hemoglobin to resealed membranes from without did not affect any of the membrane proteins. Hemin that can transport across the membrane induced, in the presence of H2O2, crosslinking of protein 4.1 and spectrin. Both free hemin and hemoglobin added with H2O2 induced crosslinking of integer cytoskeletons and mixtures of isolated cytoskeletal proteins, but hemin was always more active. Of the three major cytoskeletal proteins, spectrin and protein 4.1 were most active while the participation of actin was only minor. The yield of crosslinked products was increased in all reaction mixtures with pH, with an apparent pK above 9.0. Replacement of H2O2 by phenylhydrazine and tert-butyl hydroperoxide resulted in crosslinking of the same proteins, but with lower activity than H2O2. Bityrosines, which were identified by their specific fluorescence emission characteristics, were formed in reaction mixtures containing hemin and hydrogen peroxide and either spectrin or protein 4.1, but not actin. On the basis of fact that bityrosines were revealed only in reaction mixtures that produced protein adducts, formation of intermolecular bityrosines was analyzed to be involved in crosslinking of the cytoskeletal proteins. Since the levels of membrane-intercalated hemin are correlated with aggregation of membrane proteins, it is suggested that the peroxidative properties of hemin are responsible for its toxicity. PMID- 2241178 TI - [Epidemiology of lung cancer--recent topics]. AB - Lung cancer has been increasing markedly in recent years in Japan. It is estimated that the number of lung cancer deaths will exceed that of stomach cancer deaths by around 1995. The reason of the marked increase of lung cancer deaths is not clear, but the following factors may have contributed to the increase of lung cancer in Japan: 1) the increase in accuracy of diagnosis of lung cancer (a decrease in number of overlooked lung cancer cases), 2) an increase in number of aged population (this factor has been considered in the age adjusted mortality rate), 3) an increase in consumption of cigarettes and an increase of other risk factors of lung cancer. A number of studies have been conducted on the relationship between husband's smoking habit and lung cancer in non-smoking wives. The results of these studies implicate the effect of passive smoking on lung cancer, but more studies are needed to confirm the casual relationship. A recent study by Kawajiri et al on the DNA polymorphism of the cytochrome P450IA1 gene in lung cancer cases implicates a variation of the individual susceptibility to lung cancer. PMID- 2241179 TI - [Progress of imaging diagnosis for the cancer therapy--breast cancer]. AB - As two main modalities for the breast cancer, ultrasonography (US) and mammography (MMG) were discussed about the efficacy and limitation of qualitative diagnosis. The accuracy rate of US and MMG for the breast cancer were 90.0% and 92.7% at the Aichi Cancer Center Hospital during these 2 years (1986-1988). The number of patients with the breast cancer is increasing recently in Japan. This cancer, however, is one of the curable cancer at the early stage. Therefore, it is very important thing to detect a small malignant mass less than 1cm in a diameter by using these modalities. In addition, the establishment of the mass screening system for breast cancer is desired. In order to make a precise diagnosis, it is necessary to add some devices on the ordinary modalities. For examples, mechanical improvement of the Moribuden tube with 0.1mm focus, operation of ductgraphy and cystography by double contrast method in MMG and application of 10MHz transducer in US. Furthermore, needle biopsy under US or X ray is expected positively to make a fast diagnosis. On the other hand, DMR (Digital Mammo-Radiography) system has a bright prospect for the mass screening of the breast cancer in the respect of efficacy, cost and radiation hazard. DMR system has many advantages as follows, 1. The system is capable of bringing out clearly very minor differences of contrast. 2. Tumor shadows can be easily displayed. 3. The lateral projection only is sufficient (allowing examination of the chest wall also). 4. The X-ray dose is small: 0.03-0.05mSv. 5. The equipment is inexpensive to use. 6. Patient positioning is simple, and examinations take little time. 7. Long operator training programs are unnecessary. 8. The system uses digital signals, and so automatic diagnosis is possible. 9. Theoretically, at least, tumors as small as 0.2 mm in diameter can be detected. PMID- 2241180 TI - [Imaging diagnosis of genitourinary tract tumors]. AB - Recent advance of imaging technique have brought great advantages for management of genitourinary tract tumors. We described few examples of changes in this field from our experience. Many asymptomatic masses are discovered in the kidney and adrenal gland associated with wide clinical application of CT and US. In the kidney, the greater part of incidental masses are renal cell carcinomas (RCC) and the rate of such cases has been increasing. When small RCC is diagnosed without any clinical symptoms, better survival would be expected. Many adrenal incidental mass are also discovered by routine use of CT for abdominal workup. Since greater part of these masses are benign nonfunctioning adenomas, correct diagnosis should be made in order to avoid inappropriate surgery. Rapid development of MR also resulted in some changes in the diagnosis of urinary tract tumors. However, MR cannot be used as a screening method. For staging of RCC, intravascular or adjacent organ invasion was well determined with MR compared with CT. Differentiation of adrenal carcinomas from nonfunctioning adenomas is suggested by the difference of signal intensity on T2 weighted images. Fast spin echo scan with GD-DTPA enhancement is new MRI technique separating bladder mucosal layer from muscle layer as hyper-intensity area. Using this method, diagnostic accuracy of deep muscle invasion for bladder tumor would be improved. PMID- 2241181 TI - [Gynecologic tumor]. AB - The image diagnosis of a gynecologic tumor is progressing with the propagation of magnetic-resonance imaging (MRI), fast X-ray computed tomography (CT), and transvaginal probe. We introduce you the role which an image diagnosis should play in the decision of the therapeutic plan and the evaluation of the therapeutic effect of a uterine cervical cancer, a uterine endometrial cancer, and an ovarian cancer. In a uterine cervical cancer, MRI is useful to grasp the stage and the tumor size, and contributes toward determining a therapeutic plan. In addition, we may guess the response to the therapy, and judge the existence of a residual tumor during or immediately after an irradiation or an intraarterial injection. In a uterine endometrial cancer, MRI will contribute toward demonstrating a cervical invasion and toward assessing a myometrial invasion, therefore may help us to modify a therapeutic plan. To stage an ovarian cancer, it is necessary to visualize a small disseminated lesion. However, as all imaging modalities has a limitation to reveal the small disseminated nodules, they will not replace probe laparotomy. The probability of X-ray CT to take the place of second-look operation by an improvement has been suggested. MRI is poor at the visualization of a dissemination, however it is sometimes helpful for the evaluation of the therapeutic effect of a localizing tumor with demonstrating the changes of the signal intensity. We suppose that also an image diagnosis leaves room for expectation to contribute toward deciding the therapeutic plan of an ovarian cancer. PMID- 2241182 TI - [Cooperative research of UFT E phase II study. Cooperative Study Group of UFT E in Tohoku Area]. AB - Phase II clinical research of UFT E granules (enteric coated) was carried out in 18 institutes (21 clinical dept.) by Study Group of UFT E in Tohoku Area, to investigate its effect and safety on cancer of the digestive organs. Of all the registered 26 cases, 21 cases were available for evaluation (perfect cases: 17 and imperfect cases: 4). Patients were administered UFT E 600 mg/body/day in principle. The response rate of the overall 26 cases was 14.3% and that of perfect 17 cases was 17.6%. PR was seen in 2 cases with far advanced gastric cancer and in 1 case with sigmoid colon cancer metastasized to lung, NC in 8 cases and PD in 6 cases. Side effects more than Grade II were seen in 4 cases (19%), of which 1 case caused diarrhea with leucopenia, 1 case caused diarrhea with anorexia, fever, pigmentation, stomatitis and general tiredness, 1 case caused anorexia and the other 1 case caused paresthesia on both legs with diarrhea and anorexia. Side effects in upper digestive tract were slight, making it possible to continue administration. But 1 case, which caused simultaneously Grade II anorexia, Grade II diarrhea and Grade III paresthesia on both legs, refused administration and dropped out. He recovered from those symptoms 5 days after discontinuance of administration. UFT E is able to administer for a long term because of its slight side effects on the upper digestive tract. PMID- 2241183 TI - [Combination chemotherapy with etoposide, ADM, and CDDP (EAP) for advanced gastric cancer]. AB - EAP therapy has been performed on 50 cases of advanced gastric cancer from January 1988 to September 1989. Adriamycin 20 mg/m2, Cisplatin 40 mg/m2 and Etoposide 100 mg/m2 were administered on day 1 and 7, 2 and 8, and 4, 5 and 6, respectively, with not less than 2 courses every 3 to 4 weeks. Complete success, PR, NC and PD were obtained in 48, 21, 20 and 7 cases, respectively, the rate of effectiveness being 43.8% with a confidence interval 95% of 30-58%. The rate of effectiveness by lesions for evaluation was high (30.4, 100, and 50% for primary lesion, Virchow's lymphnodal metastasis and liver metastasis, respectively). MST was 5.1 months for EAP therapy, which was highly effective but led to no prolonged survival period. Thus, it is thought that good control of leukopenia, a dose limiting factor remains to be examined. PMID- 2241184 TI - [A multicenter clinical study of oral topical administration of G-512 on chemotherapy-associated intraoral mucosal lesions of patients with hematological malignancies. G-512 Therapeutic Study Group for Intraoral Mucosal Lesions]. AB - We evaluated the usefulness of PGE2 on chemotherapy-associated oral mucosal lesions of the patients with hematological malignancies and compared the efficacy of the troche with that of the tablet. One hundred and fifty three patients were given 0.5 mg of these PGE2 topically three times daily. One hundred and fourty five cases were evaluable (Tablet; 85, Troche; 60). 1) Symptoms and signs were improved in 102/144 (70.8%) and 102/145 (70.3%), respectively. The overall response rate was 70.3%. 2) The improvement rates were 77.5% (55/71), 85.7% (6/7) and 62.7% (32/51) in leukocyte count-increased, -unchanged and -decreased patients, respectively. 3) No background factor of the patients except performance status affected the improvement rate. 4) Higher improvement rate was noted in the PGE2 early starting group (within 5 days after the appearance of oral lesions) than the late group (6 days and thereafter) (76.5% v.s. 55.8%: U test p less than 0.1, chi2-test p less than 0.05). 5) There was no difference in the efficacy rate between the tablet and the troche. 6) Mild side effects were seen in 10 cases. These results suggest that topical administration of PGE2 is safe and useful for improving chemotherapy-associated oral mucosal lesions of patients with hematological malignancies. PMID- 2241185 TI - [Phase I study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate)]. AB - Phase I study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside (Ara-C), was conducted by cooperative study groups between January 1986 and June 1987. The dosage for the single and 5-day oral administration ranged 50 to 1,200 and 100 to 900 mg/body/day, respectively. The main adverse effects were myelo-suppression and gastrointestinal toxicities such as nausea, vomiting, anorexia and diarrhea. In the single administration, the maximum tolerated dose (MTD) could not be determined, however, in the 5-day schedule MTD was considered to be 700 to 900 mg/body/day, and the dose limiting factor to be thrombocytopenia. After the single administration (800 mg/body/day) of YNK01, the plasma concentration of Ara-C, an active metabolite of YNK01, was 3.43 ng/ml (Cmax) at 24 hrs. and 0.82 ng/ml at 72 hrs. During the 5-day administration for 300 mg/body/day and 500 mg/body/day, the Ara-C concentration changed from 2.3 to 4.1 ng/ml, and from 1.5 to 11.9 ng/ml respectively, and sustained almost the same concentration as to during the administration period until the 2nd day after the completion of the administration. PMID- 2241187 TI - [Effects of urinastatin against nephrotoxicity of cisplatinum]. AB - Nephrotoxicity is the major side effect of cisplatinum (CDDP) and it is often the dose limiting factor. We have studied the effect of urinastatin (US) to decrease the nephrotoxicity of CDDP administration. 28 patients with gynecological cancer treated by chemotherapy including CDDP (13 mg/m2 daily for 5 days) were assigned to two groups, the group with US (n = 14) and the group without US (n = 14). The former was added each 150,000 units of US before and after administration of CDDP. The BUN, serum creatinine (Cre), creatinine clearance (Ccr) and the excretion of beta 2-microglobulin (beta 2-MG) index and N-acetyl-beta glucosaminidase(NAG)index were measured. The BUN, Cre and Ccr were within normal range during four cycles. However NAG index rose remarkably when CDDP was treated by CDDP. And the increase in NAG index, which reflect the magnitude of renal tubal damage, was less in the group with US than in the group without US. It was suggested that US had effects to reduce nephrotoxicity of CDDP in chemotherapy, and that we could treat patients by high dose CDDP. PMID- 2241186 TI - [Pharmacokinetics of cis-diammine (glycolato) platinum (254-S), a new platinum antitumor agent, following an intravenous and intraperitoneal infusion bioactive platinum concentration profile]. AB - The pharmacokinetics of cis-diammine (glycolato) platinum (254-S) was investigated in cancer patients following intravenous and intraperitoneal infusion. The serum concentrations of total and unbound 254-S were determined by bioassay and chemical assay as platinum. Platinum detected by bioassay was thought to be active and unchanged 254-S. Almost all of platinum in plasma were found to be active and unbound to protein because of no differences in the concentrations determined by bioassay and chemical assay and in plasma and plasma filtrate. In abdominal ascites, platinum concentrations determined by bioassay corresponded with those determined by chemical assay, suggesting that 254-S was stable in abdominal ascites. The Cmax and AUC of active 254-S in plasma determined by bioassay following an intraperitoneal infusion were about 60% and 60-80% of those following an intravenous infusion, respectively. These results showed that 254-S was well absorbed into systemic circulation from abdominal ascites as an active form. It is concluded that antitumor effect may be obtained following an intraperitoneal infusion of 254-S as well as for the reduction of abdominal ascites. PMID- 2241188 TI - [Activity of cytochrome P450 in the stomach, with special reference to postoperative survival rate of patients with gastric cancer treated by tegafur]. AB - In routine histological preparation of gastric wall and liver specimens, immunohistochemical study of P450 was performed in the total of 116 absolutely noncurative resection of gastric cancer which followed by postoperative administration of tegafur. P450 in the liver, which considered to play a main role of tegafur activation, was strongly stained and correlated well with that of the stomach. Divided the cases into 3 groups from the degree of immunohistochemical staining of P450, postoperative survival was significantly correlated with the intensity of staining in the stomach. And the more the stage of gastric cancer advanced, the less the tissue P450 was stained. From the results obtained, reasonable consecutive administration of tegafur would be possible by immunohistochemical checking the P450 in the gastric wall. PMID- 2241189 TI - [Chemosensitivity assays for malignant gliomas]. AB - Chemosensitivity assays including colony forming assay (CFA), MTT dye reduction assay (MTT assay) and thymidine incorporation assay (TIA) for cultured rat and human glioma cells were conducted to determine the correlation among them and the in vivo antitumor efficacy of anticancer drugs using rats implanted glioma cells. Cytotoxicity of various agents such as ACNU, ACR, CDDP, VCR or BLM, was estimated from the concentrations which caused 50% inhibition of the cell growth at the peak plasma concentration. The survival time of tumor bearing rats was assessed after ip treatment with these agents at their estimated clinical doses. This parameter was greater in the drugs that were shown to be highly sensitive in CFA and was consistent with the data for CFA. In the chemosensitivity assays, CFA closely correlated to MTT assay for all agents except VCR, but poorly so to TIA. The results in this study indicate that MTT assay seemed to be useful for determining the chemosensitivity of anticancer drugs and that chemosensitivity assay should be conducted depending on the nature of anticancer drug. PMID- 2241190 TI - [A case of local recurrent breast cancer with complete response to combination of systemic chemotherapy and topical use of adriamycin ointment]. AB - A Case of local recurrent breast cancer in a 45-year-old female with complete response to Combination of chemotherapy and topical administration of Adriamycin is reported. The patient had left mastectomy for breast cancer in 1978, and then right mastectomy for breast cancer in 1987. Two years later, she was readmitted to our hospital with right neck lymph node metastasis and local recurrence at right chest wall. Neck lymph node metastasis was treated with irradiation with good response. On the other hand, Adriamycin ointment was applied to recurrent cancer on the right chest. The cancer was gradually diminished in size. Seventy eight days after treatment, the local chest wall with cancer was resected. Histologically, the entire resected tissue showed no viable cancer cells and Adriamycin concentration in the tissue was extraordinary high (ten to forty fold over on systemic chemotherapy). Adriamycin ointment may be an alternative treatment of choice for local recurrent breast cancer. PMID- 2241191 TI - [A case of recurrent ovarian cancer markedly responding to daily oral administration of low dose etoposide]. AB - A 67-year-old woman with recurrent ovarian cancer, who had carcinomatous peritonitis and large abdominal cystic lesions, was treated by daily oral etoposide at a dose of 50 mg/day for 21 consecutive days at 2-week intervals in the outpatient department. After 15 days of administration, the serum level of CA125 decreased from 2,220U/ml to 445U/ml, and that of LDH from 2,725 WU to 906 WU. After the third course of treatment, the abdominal cystic lesions were remarkably reduced, and the performance status improved grade 1 from 3 prior to the administration. No severe side effects except for alopecia and mild myelosuppression were noted during the 3-month treatment. PMID- 2241192 TI - [A case of early gastric carcinoma which disappeared with treatment of low dose 5 FU]. AB - A 60-year-old male with early gastric carcinoma of Ha type, had received colectomy for his carcinoma in transverse colon. He was treated after operation with 5-Fluorouracil (5-FU) orally at 200 mg per day. One and a half month after operation at a total dose 8.4 g 5-FU, the patient was examined on his stomach by endoscope and barium enema. The polypoid tumor in the stomach was not recognized there. No lesion has been noticed in his stomach endoscopically in the following 1 year. PMID- 2241193 TI - [Protective effect of urinastatin on cisplatin-induced cytotoxicity in the renal tubules]. PMID- 2241194 TI - [Tumor marker: practical usage of tumor marker for recurrent breast cancer--our experience]. AB - The point of practical usage of monitoring tumor marker, CEA and CA15-3, for breast cancer patients was indicated and discussed. We presented several cases with recurrent breast cancer patients and verified the practical usefulness of monitoring tumor marker, CEA and CA15-3. Fundamental changing pattern of these markers in serum on semi-logarithmic graph was exhibited to show linear pattern and the two curves of CEA and CA15-3 kept basically parallel except several conditions, when both markers were positive. From the graphical changes of markers we could made early and correct judgement of the effect of the treatment. However, there existed several cases who showed strange and paradoxical changing pattern of these markers apart from clinical courses. That is the situation that heterogenetic changes of the tumor or tumor lysis syndrome are taken place. It was emphasized that the value of serum tumor markers should be taken notice of the changes of markers in these situations. PMID- 2241195 TI - Modified nasolabial transposition flap provides vestibular lining and cover of alar defect with intact rim. PMID- 2241196 TI - The nasolabial flap as a single-stage procedure. AB - The nasolabial flap is a useful reconstructive technique for the repair of defects on the nose. An improved technique used in 32 patients is presented, which allows use of this procedure as a single-stage rather than the more commonly seen two-stage procedure. The alterations include the following: (1) the excision of a Burow's triangle superior edge of the defect toward the inner canthus; (2) the use of a periosteal or suspension suture to minimize tenting across the concave junction of the nose and cheek; (3) wide undermining of the skin surrounding the defect to create a stabilizing platelike scar; (4) significant thinning of the donor flap; and (5) adjust the size of the flap to recreate the original preincisional skin tension on the flap after suturing. None of the 32 patients presented required a second-stage procedure to correct trapdoor defects or to recreate natural folds or creases. PMID- 2241197 TI - Cutaneous T-cell lymphoma (parapsoriasis en plaque). An association with pityriasis lichenoides et varioliformis acuta in young children. AB - Pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC) are related benign disorders without recognized association with cutaneous T-cell lymphoma (CTCL). We report the cases of two children with documented PLEVA evolving into CTCL over several years. One child had the clinical lesions of PLC but the dermatopathologic findings of PLEVA at age 2 years. At age 12 years, he had skin changes of poikiloderma atrophicans vasculare and dermatopathologic findings consistent with parapsoriasis en plaque. The second child presented at age 7 years with scaling dermatitis and dermatopathologic findings of PLEVA. At age 12 years, the histologic diagnosis was parapsoriasis. Monoclonal antibody studies performed on biopsy specimens from both patients revealed 70% to 100% cells staining with CD5, 80% to 90% staining with CD4, 30% to 50% staining with CD8, and an increase in CD1-staining cells in the papillary dermis, indicating a predominantly helper T-cell infiltrate. We believe that PLC and PLEVA may be part of the spectrum of CTCL. Furthermore, CTCL may be more common in young children than once thought. PMID- 2241198 TI - Characterization of the dermal infiltrate in human immunodeficiency virus infected patients with psoriasis. AB - We investigated the dermal inflammatory cell infiltrates of psoriatic lesions from nine human immunodeficiency virus-infected patients and nine age-, sex-, and site-matched control specimens. The study was retrospective and observer blinded. T lymphocytes were quantitated using UCHL-1, a pan-T-cell monoclonal antibody, and plasma cell number was estimated in hematoxylin-eosin-stained sections. Differences in both variables reached statistical significance. There were fewer T cells and the number of plasma cells was significantly higher in specimens from the human immunodeficiency virus-positive individuals in comparison with control specimens. As plasma cells are readily identified on hematoxylin-eosin-stained sections, their presence in skin biopsy specimens from psoriatic leisons should arouse suspicion of human immunodeficiency virus infection. The depletion of helper/inducer T lymphocytes by the human immunodeficiency virus may promote the presence of plasma cells in cutaneous inflammatory infiltrates. PMID- 2241199 TI - Cicatricial pemphigoid. Identification of two distinct sets of epidermal antigens by IgA and IgG class circulating autoantibodies. AB - A patient with severe cicatricial pemphigoid demonstrated both in vivo bound and circulating anti-basement membrane zone antibodies of the IgA and IgG classes. Complement component 3 (C3) was also deposited in the basement membrane zone of lesional skin as well as in normal-appearing buccal mucosa of the patient. However, C1q was absent, while granular deposits of two factors of the alternative complement activating pathway, properdin and properdin factor B, were present only in the basement membrane zone of lesional skin, but not in normal buccal mucosa. Deposition of alternative complement pathway reactants in the lesion suggests that complement activation by IgA was associated with lesion development. Western blot analysis of the patient's serum on electrophoresed cultured keratinocyte antigens identified two distinct sets of epidermal antigens. While IgG bound antigens of 230, 205, 140, and 90 kd, the patient's IgA antibodies bound a distinct set of antigens, 180 and 130 kd. The potential pathogenic role of IgA in cicatricial pemphigoid is discussed. PMID- 2241200 TI - Dermatitis herpetiformis bodies. Ultrastructural study on the skin of patients using direct preembedding immunogold labeling. AB - Skin samples from three adult patients with dermatitis herpetiformis (DH) and granular IgA deposits in the papillary tips were studied using ultrastructural immunogold technique. IgA positive, so-called DH bodies were identified as amorphous clumps--most probably immunocomplex aggregates--scattered throughout the upper papillary dermis. Dermatitis herpetiformis bodies were seen underneath the basement membrane, sometimes along microfibrillar bundles, as well as adjacent to the papillary collagen fibers and within the surface (microfibrillar) region of elastic tissue. Some DH bodies, however, were not related to any fibrillar components. The collagen and elastic fibers, microfibrillar bundles, anchoring fibrils, and elastic microfibrils themselves were unlabeled. Dermatitis herpetiformis bodies were not found in normal human skin. The results of our ultrastructural study indicate that DH bodies either are bound to a nonfibrillar component of dermal connective tissue or represent deposits of immune complexes trapped in DH skin. PMID- 2241201 TI - The familial occurrence of bullous mastocytosis (diffuse cutaneous mastocytosis). AB - We studied four patients (a mother, her two daughters, and her son) with bullous mastocytosis, or diffuse cutaneous mastocytosis, whose genetic inheritance suggested an autosomal dominant pattern. The clinical characteristics included extensive bullae, numerous urticaria, pruritus, flushing, and pseudolichenified skin over all body surfaces without systemic organ involvement. The histopathologic findings disclosed a pronounced accumulation of mast cells in the dermis. Electron microscopic studies of lesional skin obtained in infancy showed round or spindle-shaped mast cells with numerous fingerlike villous protrusions. The cytoplasmic granules varied in size and shape, and the appearance of degranulation was markedly noted. In the adult, most mast cells had markedly decreased numbers of granules and cytoplasmic villi. Some cells displayed degenerative or necrotic appearances. These findings correlated well with the clinical course of these cases, which improved spontaneously over time. PMID- 2241202 TI - Ichthyosis, mental retardation, and asymptomatic spasticity. A new neurocutaneous syndrome with normal fatty alcohol:NAD+ oxidoreductase activity. AB - A number of inherited disorders of cornification have been related to abnormal lipid metabolism. In the recessively inherited Sjogren-Larsson syndrome, defined by the triad of ichthyosis, mental retardation, and spasticity, fatty alcohol:NAD+ oxidoreductase deficiency has recently been reported. These patients accumulate fatty alcohol in the plasma and cultured fibroblasts. A 19-year-old woman with ichthyosis, mental retardation, and mild spasticity is described in whom fatty alcohol metabolism was normal, as determined by plasma octadecanol level and fibroblast fatty alcohol:NAD+ oxidoreductase activity. Ultrastructural studies on skin from the patient revealed morphologically abnormal epidermal lamellar bodies, not unlike those seen in neutral lipid storage disease with ichthyosis. We postulate that this patient has a novel neurocutaneous syndrome that may be secondary to abnormal lipid metabolism. PMID- 2241203 TI - Dermatology in the German Democratic Republic. PMID- 2241204 TI - Current status of dermatologic surgery: new special requirements for dermatology residency training. PMID- 2241205 TI - A pruritic vesicular eruption. Henoch-Schonlein purpura. PMID- 2241206 TI - Purpuric vesicular eruption in a 7-year-old girl. Vesicular pityriasis rosea. PMID- 2241207 TI - Urticarial skin eruption in a child. Leukemia cutis. PMID- 2241208 TI - Psoriasis induced at the injection site of recombinant interferons. PMID- 2241209 TI - Pruritic urticarial papules and plaques of pregnancy are not related to maternal or fetal weight gain. PMID- 2241210 TI - Cutaneous mucinosis in a patient with eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. PMID- 2241211 TI - Dermal mucinosis in the eosinophilia-myalgia syndrome. PMID- 2241212 TI - Thrombocytopenia-absent radii syndrome and lack of response to the pulsed dye laser. PMID- 2241214 TI - Pemphigoid nodularis. PMID- 2241213 TI - Follow-up study of a cutaneous adult T-cell leukemia/lymphoma patient by southern blot analysis. PMID- 2241215 TI - Psoriasis after allogeneic bone marrow transplantation. PMID- 2241216 TI - A family outbreak of acute guttate psoriasis. PMID- 2241217 TI - Acral pseudolymphomatous angiokeratoma of children. PMID- 2241218 TI - Genomic imprinting. PMID- 2241219 TI - Neonatal infections with coagulase negative staphylococci. PMID- 2241220 TI - Prediction of acute renal failure after birth asphyxia. AB - Twenty-one babies of 34-41 weeks' gestational age with birth asphyxia (5 minute Apgar score less than or equal to 5 or umbilical artery pH less than or equal to 7.2) were studied during the first two days of life to find out whether the urinary excretion of tubular markers of renal function is of value in the early diagnosis of acute renal failure. Urinary retinol binding protein, myoglobin, and N-acetyl-beta-D-glucosaminidase (NAG), expressed as a ratio with urinary creatinine, were measured and excretion profiles repeated at 3-6 days in 15 infants and at 7-14 days in 11 infants. Plasma creatinine concentration, creatinine clearance, plasma myoglobin concentration, and fractional sodium excretion were measured where possible in asphyxiated infants. Control data were obtained from 50 healthy infants: 28 gave urine samples alone, 17 urine and blood, and five blood alone. Normal urinary values were derived from 17, 25, and three infants, respectively, for the three time periods. The number of control samples was limited for ethical reasons. Four asphyxiated infants had acute renal failure (group 1), four had tubular dysfunction without glomerular disturbance (group 2) and 13 had normal renal function (group 3). Group 1 were clearly identified by greatly increased urinary retinol binding protein (greater than 27,000 micrograms/mmol creatinine) and myoglobin (greater than 1500 micrograms/mmol creatinine) excretion measured in the first two days of life. In control infants the range of excretion of retinol binding protein within the same time period was 3 to 967 micrograms/mmol creatinine and urinary myoglobin was undetectable. Excretion of NAG failed to discriminate between groups 1 and 2. Acute renal failure occurred only in infants who had heavy myoglobinaemia. Tubular dysfunction in group 2 was transient and not accompanied by plasma electrolyte disturbances. We conclude that measurement of urinary excretion of retinol binding protein or myoglobin after birth is helpful in the early diagnosis of acute renal failure. PMID- 2241221 TI - Area of lateral ventricles measured on cranial ultrasonography in preterm infants: reference range. AB - Serial ultrasound imaging of the brain was carried out in 87 preterm infants of 27 to 36 weeks' gestational age while they were in the special care nursery and during their first postnatal year. None had evidence of intracranial disease during the neonatal period and 94% had good neurodevelopmental outcome at 2 years of age. Lateral ventricle area measurements were plotted against independent variables including postnatal age and head circumference at the time of the examination. The measurements increased as age and head circumference increased. During the first six weeks of life the mean (SD) postnatal head circumference growth velocity (rate of growth) was 0.53 (0.13) cm/week and the mean postnatal ventricular area growth velocity was 0.39 (0.19) mm2/week. A reference range for lateral ventricle area values was developed from these serial measurements in infants with documented good short term developmental outcome. PMID- 2241222 TI - Spontaneous resolution of bone mineral depletion in preterm infants. AB - Fifteen preterm infants and 17 born at full term whose gestational ages ranged from 25 to 34 weeks and 38 to 42 weeks, respectively, were examined initially at postconceptional ages ranging from 38 to 44 weeks and subsequently at 46 to 71 weeks. Each examination included measurement of bone mineral content of the mid forearm by single photon absorptiometry. For the preterm group, the mean (SD) value of bone mineral content at the first examination was 109.0 (27.6) mg/cm and was significantly lower than the corresponding value of 194.4 (19.6) mg/cm for the whole full term group. The mean subsequent rate of mineral accretion in the preterm group was 8.70 (4.60) mg/cm/week, the mean individual duration of observation being 9.7 weeks. Rate of mineral accretion for the full term group was independent of the duration of observation and averaged 1.60 (2.20) mg/cm/week. The difference between mean values of rate of mineral accretion in the preterm and full term groups was highly significant. Our results show that there is a phase of rapid mineral accretion starting at 40 weeks' postconception in preterm infants that substantially reduces the perinatal mineralisation deficit. PMID- 2241223 TI - Preoperative stabilisation in congenital diaphragmatic hernia. AB - Between January 1983 and November 1986, 26 newborn infants with congenital diaphragmatic hernia were treated by early operation at a mean of 7 hours of age. A further 23 infants admitted between December 1986 and December 1989 were stabilised for a mean period of 40 hours before operation. There was no significant difference in survival between the two groups. Delayed operation is not detrimental to infants with congenital diaphragmatic hernia. PMID- 2241224 TI - Peak inspiratory pressure requirements in infants born weighing less than 750 g. AB - The possibility that peak inspiratory pressure requirements or the arterial:alveolar oxygen ratio can predict the clinical outcome in infants weighing less than 750 g at birth was explored in a consecutive series. Nine of 10 infants (90%) with a peak inspiratory pressure requirement of more than 18 cm H2O at 48 hours or more than 16 cm H2O at 72 hours from age subsequently died later of respiratory causes (defined as death after 72 hours of pulmonary interstitial emphysema, bronchopulmonary dysplasia, or cor pulmonale). Twenty of 21 remaining infants (95%) survived until discharge. Using these data a 95th centile for peak inspiratory pressure requirement during the first 72 hours of life was constructed. The potential value of this centile in predicting later death of respiratory causes was examined in a separate series. Twelve of 15 infants (80%) whose peak inspiratory pressure requirements remained below the 95th centile, or were not ventilated (n = 6), survived. In contrast, 11 of 12 (92%) infants whose requirements crossed the 95th centile died later of respiratory causes. The infants who died had more radiological changes and higher mean arterial carbon dioxide pressure than survivors suggesting that the severity of the initial lung disease rather than the way that ventilation was managed determined prognosis. Peak inspiratory pressure requirement was more useful than arterial:alveolar oxygen ratio in clearly distinguishing between survivors and infants who died later of respiratory causes. PMID- 2241225 TI - Amniotic fluid insulin concentration as a predictor of obesity. AB - Longitudinal correlations were obtained between amniotic fluid insulin concentration at 32 to 38 weeks' gestation and anthropometric characteristics at the age of 6 years in 56 children of diabetic mothers. The prospective studies indicated that at the age of 6 years, as at birth, the greatest increase in weight in relation to height (relative obesity) was seen in children who experienced the greatest exposures to insulin in the uterus (as judged by amniotic fluid insulin concentration). Significant correlations between amniotic fluid insulin and relative obesity at the age of 6 years were found after adjustment for maternal obesity and macrosomia at birth. The highest amniotic fluid insulin values are clustered in the subgroup of 14 children who were obviously obese by the age of 6 years. These findings are consistent with the hypothesis that there is an association between anthropometric development and intrauterine metabolism, and suggest that premature and excessive exposure to insulin during gestation may predispose to obesity in childhood. The amniotic fluid insulin concentration may predict this eventuality. PMID- 2241226 TI - Ramadan and birth weight at full term in Asian Moslem pregnant women in Birmingham. AB - The birth weights of 13,351 babies born at full term from 1964-84 to Asian Moslem mothers in Birmingham were analysed to see if the effect of the Ramadan fast on maternal biochemical profiles was of any clinical relevance. These were compared with two age matched control groups comprising white and non-Moslem Asian babies. Ramadan had no effect on mean birth weight at whatever stage of pregnancy it occurred. There was an increase in the prevalence of low birth weights (4.5% to 8%) among babies who were born at full term when Ramadan had occurred during the second trimester, but this was not significant. We conclude that the Ramadan fast has no effect on the birth weights of babies born at full term. PMID- 2241227 TI - Outcome after acute osteomyelitis in preterm infants. AB - Eight cases of skeletal infection in preterm infants were studied. All the infants were systemically unwell, with polymorpholeucocytosis. Diagnosis was by blood culture, and any radiographic changes were apparent at the time of presentation. Infection was often multifocal, with sites around the knee being most commonly affected. Staphylococcus aureus was the pathogen isolated in six of the eight cases; in these treatment with fusidic acid was effective and well tolerated, even at doses that were less than the recommended therapeutic minimum. Even with prompt diagnosis and aggressive treatment orthopaedic sequelae are common. PMID- 2241228 TI - Skin conductance and arousal in the newborn. AB - We measured skin conductance continuously from the sole of a foot in babies of different conceptional ages before, during, and for 10 minutes after a 'heel prick' carried out for routine blood sampling. We studied 82 healthy babies whose gestational and postnatal ages ranged from 25-42 weeks, and 1-73 days. The median skin conductance level (preheel prick) in babies of 40-43 weeks' conceptional age was 0.6 microS (microsiemens) and differed significantly between awake babies (1.2 microS) and those who were asleep (0.5 microS). In contrast babies less than 40 weeks had a significantly lower median skin conductive level (0.3 microS) which was identical in awake and asleep babies. In response to the heel prick all babies became aroused and skin conductance rose sharply and immediately in 21 out of 22 (95%) babies 40-43 weeks' conceptional age, and in seven out of 23 (30%) babies 36-39 weeks. The median rise at one minute in babies of 40-43 weeks was significantly higher than those 36-39 weeks (2.7 microS compared with 0.5 microS). No babies less than 36 weeks had a change in their skin conductance after the heel prick. These results are consistent with the notion that 'emotional sweating' is a function of maturity and does not develop until 36 weeks' conceptional age. PMID- 2241229 TI - Gut blood flow velocities in the newborn: effects of patent ductus arteriosus and parenteral indomethacin. AB - The effects on gut blood flow velocities of parenteral indomethacin (0.2 mg/kg) given either quickly as a bolus or slowly as an infusion were compared in consecutive studies of two groups of infants with symptomatic patent ductus arteriosus. In the presence of patent ductus arteriosus the range of velocities in the superior mesenteric artery before indomethacin was given was characterised by pronounced abnormalities including absent--or in some cases even retrograde- diastolic flow. In eight subjects the first rapidly given bolus dose of indomethacin (duration 20 seconds or less) caused a pronounced and sustained fall in the velocity of the superior mesenteric artery blood flow (mean peak systolic velocity (cm/second): before 74; after 38; median time to maximum fall 7.4 minutes; median time to recovery 50 minutes). A further 10 subjects received their first dose of indomethacin by slow infusion (duration 30-35 min) and the percentage fall in peak systolic velocity was both substantially less (22% compared with 47%) and later (median time to maximum fall 37.3 minutes) than after rapid infusion. Qualitatively similar but smaller changes were seen in the coeliac axis. Return of antegrade end diastolic flow in the superior mesenteric artery within one hour of the first dose of indomethacin was a good predictor of subsequent closure of the ductus. These data suggest that there is a profound disturbance in mid gut perfusion in infants with patent ductus, which is exacerbated by indomethacin given rapidly by intravenous bolus. They may also provide a rational explanation for the well recognised association between necrotising enterocolitis and both patent ductus arteriosus and indomethacin administration. The unwanted effects of the indomethacin are abrogated by slow infusion, without loss of efficacy in closure of the ductus. PMID- 2241230 TI - Hiccups and breathing in human fetuses. AB - Serial recording in 45 low risk fetuses throughout the second and third trimesters showed that hiccups were the predominant diaphragmatic movement before 26 weeks' gestational age and that there was a significant negative correlation with gestational age. There was a pronounced reduction between 24 and 26 weeks, which was the result of a decrease in the number of episodes of hiccups rather than a change in the duration of episodes. In contrast, fetal breathing was positively correlated with gestational age, the greatest increase in breathing occurring between 26 and 32 weeks' gestation. This was the result of both an increase in the number and duration of episodes. From the time that rest-activity cycles of behaviour could be determined in recordings, both breathing and hiccups were dependent on behavioural state or cycle, occurring predominantly during active episodes. This association between quiet and active behaviour and breathing did not alter with increasing gestational age, and the variables in fetal behavioural state became increasingly closely linked. The importance of prolonged and repeated recording, and also the need to take account of other variables in fetal behaviour, before any sinister conclusions can be drawn about the absence of fetal breathing is emphasised. PMID- 2241232 TI - Bronchopulmonary dysplasia: early diagnosis, prophylaxis, and treatment. PMID- 2241231 TI - Bronchopulmonary dysplasia: then and now. PMID- 2241234 TI - Withdrawal of life support in babies: deceptive signals. PMID- 2241233 TI - Bronchopulmonary dysplasia: a new look at management. PMID- 2241235 TI - Dr William Harvey (1578-1657): physician, obstetrician, and fetal physiologist. PMID- 2241236 TI - Chlorinated hydrocarbons in fat tissue: analyses of residues in healthy children, tumor patients, and malformed children. AB - The content of chlorinated hydrocarbons (CHC) was determined by means of capillary column gas chromatography in samples of fat tissue from 183 healthy children, 46 children with malignant tumors and 33 children with benign tumors or congenital malformations. The highest concentrations were found for total polychlorobiphenyls (PCB) (mean = 1.614 ppm), followed by the DDT group (mean = 0.556 ppm, HCB (mean = 0.097 ppm), the HCH isomers (mean = 0.083 ppm), dieldrin (mean = 0.020 ppm) and total heptachlor (mean = 0.010 ppm). Neonates displayed high concentrations in the adipose tissue before the first uptake of food. In the first six months of life, the concentrations of total PCB, the individual PCB components as well as DDT and HCB decreased significantly. In the second year of life, they rose again to the initial values and then remained relatively constant during the rest of childhood. The regional differences with regard to total CHC residues were slight, so that the CHC exposure cannot be reduced by a change of domicile within West Germany (FRG). Children with congenital malformations or benign or malignant tumors do not display raised concentrations of CHC. PMID- 2241237 TI - Biological monitoring of human exposure to acephate. AB - Acephate is a water-soluble organophosphate insecticide whose action on insects has been related to its conversion to methamidophos, a very potent anticholinesterase agent which has caused delayed neuropathy in man. Inhalation and skin exposure to acephate was evaluated in four workers engaged in 8-day campaigns with the formulation of the 97%-pure technical product. Before, during, and after exposure, the workers were monitored for the urine content of acephate and methamidophos, and for erythrocyte (AChE) and plasma (PChE) cholinesterase levels. Median air concentrations (8-hr TWA) ranged from 0.278 to 2.170 mg/m3; median total-body skin deposition ranged from 26.1 to 41.9 mg/day. Based on these values, daily workers' absorption of acephate was estimated to be in the order of 10-20 mg. Urinary excretion of unchanged acephate followed a pattern consistent with exposure, showing peak values of excretion during the workshift or in the eight hr after the end of the workshift. The urine levels of unchanged acephate were found to vary from 1 to 10 mg/L. Methamidophos was not detected in any urine sample (detection limit: 30 micrograms/L). High correlation (r = 0.78) was found between skin exposure level and urine acephate elimination. No changes in AChE or PChE were observed for the workers whose urinary concentrations of acephate were 1 or 2 mg/L. One subject who had urinary acephate excretion between 3 and 8 mg/L, showed slightly decreased values of PChE during exposure and of AChE after exposure. PMID- 2241238 TI - The effect of copper on the embryonic development and hatching of Sepia officinalis L. AB - The influence of copper on embryonic development and hatching of Sepia offinalis was investigated. Copper exerts a profound effect on both hatching stage and time to-hatching. At high copper concentrations (50-200 ppb Cu2+), the embryos hatch earlier than the controls but have a lower survival potential. No external morphological malformations were found. Whereas copper does not accumulate in the embryo or in the vitellus, it is absorbed by the envelope and/or the chorion. PMID- 2241239 TI - Children in out-of-home placement: a psychiatric nursing challenge. PMID- 2241240 TI - The use of touch with the hospitalized psychiatric patient. AB - A descriptive study was designed to identify and describe the ways in which registered nurses use nonprocedural touch in the inpatient psychiatric setting. Natural setting observation and nurse interviews were used to examine the decision-making process and intentions of nurses who used touch. Twenty-five incidents of nonprocedural touch initiated by 13 registered nurses with 17 psychiatric patients were recorded over 27.5 hours of observations. Touch was primarily used by nurses in a discriminating manner and for specific reasons, and was correlated with numerous factors such as the patient's age and gender, and the nurse's feelings, beliefs, intuition, and personal style. PMID- 2241241 TI - Forced relocation of hospitalized psychiatric patients. AB - By virtue of their disability and hospital program requirements, severely and chronically mentally ill patients are subject to involuntary transfer from the community to hospitals, within hospitals, between hospitals, and from hospitals to the community. These forced relocations, no matter how humanely they were initially conceived to be, have become highly routine. The consequence is loss of the sense of the patient as a human being with individual needs. This research elicited the patients' own descriptions and the meanings they attached to the experience of forced relocation. The findings point to the need for greater success of programs designed to keep patients in their home communities to the greatest extent possible. The findings also suggest the need for hospital staff to eliminate or reduce intrahospital transfers and to develop and maintain humane transfer procedures when forced relocation becomes necessary. PMID- 2241242 TI - A family systems model for divorce and the loss of self. AB - The dissolution of a marriage through divorce represents a major loss in the lives of all family members. Losses can include those of a physical, social, and emotional nature. The self as it was defined within the marital context and the loss of that self as a result of divorce is a significant source of potential dysfunction in adult family members during and after the divorce. From a family systems' perspective, the lower the level fo differentiation of self in family members, the greater is the likelihood that the self was defined in a fusional way during the marriage. As such, when the fused common self is lost through divorce, one or both spouses is likely to experience a significant sense of loss as well as potential dysfunction. The purpose of this article is to propose a model that helps divorced people deal with the loss of self and assists them to define a more differentiated sense of self. PMID- 2241243 TI - Assessment and management of depression: an imperative for community-based practice. AB - The purpose of this mental health training program was to increase primary care nurses' knowledge and skills about depression. The program emphasized criteria for assessing depression, presented psychopharmacological and psychotherapeutic content, discussed care coordination among multiple agencies and providers, and addressed referral resources. Highlighted were cultural and developmental issues for Native Americans, Mexican-Americans, the elderly, and adolescents. The training program successfully increased primary care nurses' knowledge about depression and their abilities to use this knowledge in clinical practice. PMID- 2241244 TI - A psychogeriatric nursing assessment protocol for use in multidisciplinary practice. AB - The assessment of geriatric patients with psychiatric or neurobehavioral problems demands a multidisciplinary approach linking nursing, psychiatry, neurology, geriatrics, and internal medicine. While the medical disciplines have relatively well-established approaches to assessing psychogeriatric patients, nursing lacks a comprehensive assessment strategy that supports both nursing and multidisciplinary practice. This article describes the Psychogeriatric Nursing Assessment Protocol (Abraham, 1989) developed for use in a multidisciplinary geriatric neuropsychiatric outpatient clinic. The relationship of the protocol to psychiatric, neurological, geriatric, and medical assessments is discussed in an attempt to clarify the linkages of knowledge and care required for successful service delivery to geriatric patients with psychiatric or neurobehavioral problems, as well as to their families and formal and informal caregivers. PMID- 2241245 TI - Psychiatric-mental health head nurse management concerns. AB - Psychiatric-mental health head nurses supervise and direct patient care, and therefore, possess a critical, front-line perspective of nursing practice problems. This article explores this perspective by interviewing four head nurses about patient care, staffing, and organizational management concerns. Interestingly, some of the findings of the study, such as head nurse concerns regarding retaining, recruiting, and motivating staff, and increasing patient acuity, already have been supported in the general nursing literature. Other concerns, including the need to clarify the role of the nurse and to define areas of responsibility with other mental health professionals, seem unique to mental health nursing. PMID- 2241246 TI - Consultee satisfaction with a psychiatric consultation-liaison nursing service. AB - A consumer satisfaction survey was conducted with nurses who made consecutive consultation requests to a general hospital psychiatric consultation-liaison nursing service. In each of 69 responses, global satisfaction ratings indicated that the consultee either was satisfied or very satisfied with the assistance provided. Particular strengths were noted in relation to the ease with which the consultants could be notified, the speed of response, and the clarity with which their formulations were expressed. The respondents were least satisfied with the extent of written documentation and the amount of follow-up. In a multiple regression analysis, only the total number of visits emerged as a significant predictor of satisfaction scores. However, comparisons of replies of most satisfied and least satisfied also indicated that high satisfaction ratings were more likely to be given to consultations requesting assistance with patients' families rather than to consultations requesting help in the management of patients with major psychiatric disorders. PMID- 2241247 TI - Loneliness in veterans with AIDS and its relationship to the development of infections. AB - The purposes of this study were to examine loneliness in men with AIDS over a 6 month period and relate the extent of loneliness to the development of infections. Psychoneuroimmunology theory suggests that emotional distress alters immune response. It was believed that loneliness would increase vulnerability to infection. A convenience sample of 31 veterans participated in the study. Although there were no significant changes in loneliness over the 6-month period for the total sample, gay men had a significant increase (P greater than .03) in loneliness related to romantic sexual attachment. Despite an average of 3.4 infections over the 6-month period, there was no relationship between development of infection and loneliness. Factor analysis was performed for the demographic and study variables. The three factors identified from the study variables were loneliness, social support, and vitality. PMID- 2241249 TI - A passion for people, quality, and service. PMID- 2241248 TI - Clozapine: a new antipsychotic drug. AB - Clozapine is a new antipsychotic drug that displays antipsychotic efficacy of the classic neuroleptics without the associated extrapyramidal side effects. This article briefly reviews the action and use of clozapine in order to help nurse clinicians become familiar with the drug usage. Clozapine is presently in use only in clinical trials, but is expected to be marketed by Sandoz Pharmaceutical Corporation (Hanover, NJ) in 1990. PMID- 2241250 TI - Nursing, quality, and health policy: a partnership for change. AB - In this article, Kathryn M. Mershon, MSN, RN, CNAA, senior vice president for nursing at Humana Inc. and a member of the Prospective Payment Assessment Commission (ProPAC), examines several ideas or initiatives that need to be explored to help advance nursing to where it should be in the future. These include among others getting rid of "sacred cows" that impede change, understanding nursing's influence on health policy reform, examining quality in the current health care environment, and implementing steps for future change. PMID- 2241251 TI - Certification in nephrology nursing: an interview with NNCB president Janel Parker. Interview by Patricia S Jordan. AB - Certification in nephrology nursing became a reality in 1987 with the formation of the Nephrology Nursing Certification Board (NNCB), and the development and administration of the nephrology nursing certification examination. Three years later, NNCB President Janel Parker discusses the evolution of the NNCB examination, the significance and impact of the examination, and the future of certification in nephrology nursing. PMID- 2241253 TI - A dialysis patient classification system for establishing nurse/patient ratios. AB - In Connecticut, dialysis-related patient classification systems have taken on greater significance as state regulations deemphasize traditional nurse/patient ratios. The patient classification system devised for the Rockville General Hospital End Stage Renal Disease Unit is based on a process-oriented system and addresses both the physiologic and psychologic needs of the patient. Use of the system has provided nurses with a more efficient and effective means of matching patient care needs with daily staffing assignments. This article addresses the development of a patient classification system tool and the validity and reliability studies conducted to test the tool. PMID- 2241252 TI - Life satisfaction and coping of diabetic hemodialysis patients. AB - End-stage diabetic patients who are dependent on hemodialysis live with multiple deficits and discomforts. Their quality of life would seem dismal to others. The perceptions of the patients themselves, however, might be quite different. In this descriptive study, 12 such patients were interviewed using Cantril's Self Anchoring Striving Scale. The mean satisfaction rating for the anticipated future was almost as high as the past, despite experiencing a long-standing downward health spiral. Content analysis of the interviews suggested coping patterns of people who are living with a chronic disease. PMID- 2241255 TI - Care of the family of the child with end stage renal disease. AB - A major challenge for the pediatric nephrology nurse is to build a relationship with the family of the child with end stage renal disease (ESRD) that is neither intrusive nor fosters overdependence. Strategies addressed in this article include assessment, the team approach, teaching, emotional support, counseling, and coping with the health care system. PMID- 2241254 TI - Cultural considerations in teaching the Saudi Arabian renal transplant recipient. AB - Teaching renal transplant recipients in Saudi Arabia requires incorporation of basic nursing principles with cultural and religious beliefs to develop individualized plans of care. Multinational nursing staffs collaborate on teaching methods and materials to promote compliance with diet, medications, and activities to return the transplant patient to health and a normal lifestyle. PMID- 2241256 TI - Spice of life: a strategy to enhance dietary compliance. AB - A creative teaching strategy was implemented to stimulate patients' motivation to incorporate learned dietary concepts into their daily life-style. Thirty-five hemodialysis patients were given a pamphlet that described herbs and spices to enhance the flavor of specific foods and 25 sample seasoning packets for their experimentation. Most stated that the pamphlet was helpful (82.9%) and use of the spices made the diet palatable 75% or more of the time (93.4%). PMID- 2241258 TI - "Women working with women" session lacked 'sensitivity'. PMID- 2241257 TI - Case management of the anemic patient. Epoetin alfa: focus on nutrition management. AB - As the use of Epoetin alfa to treat the anemia of chronic renal failure expands, attention is beginning to focus on the dietary changes that may occur subsequent to therapy. The anemia-related pattern of poor appetite, lethargy, and decreased mental and physical status can often be reversed as anemia is corrected. Changes in nutritional status increase the importance of monitoring serum chemistries and providing timely interventions. Potentially serious side effects associated with changes in serum chemistries can be minimized or prevented by a teamwork approach involving the physician, nurse, and renal dietitian. PMID- 2241259 TI - A tribute to nephrology nurses. PMID- 2241260 TI - The ANCA test: its clinical relevance. PMID- 2241261 TI - Oral contraceptives and rheumatoid arthritis: new data from the Royal College of General Practitioners' oral contraception study. AB - From data available at April 1987 it was found that the standardised risk ratio for rheumatoid arthritis between current users of oral contraceptives and never users was 0.82 (95% confidence interval 0.59 to 1.15); the ratio between former users and never users was 0.94 (95% confidence interval 0.72 to 1.22). Important secular trends have occurred within our study population. The incidence of rheumatoid arthritis among former and never users has declined over the past two decades. Current users have not experienced this temporal trend, and the ratio between current and never users has, therefore, approached unity. These secular changes may explain why some studies have found that oral contraceptives have a protective effect, while others have been unable to show such an effect. PMID- 2241262 TI - Measurement of the chemotactic complement fragment C5a in rheumatoid synovial fluids by radioimmunoassay: role of C5a in the acute inflammatory phase. AB - Evidence suggests that complement is activated in rheumatoid joints. A sensitive radioimmunoassay for the activation fragment of C5, C5a, which is a potent chemoattractant for neutrophils, was therefore developed. A mean C5a concentration in 22 rheumatoid joint fluids of about 2.5 x 10(-9) mol/l was found. This concentration of C5a is sufficient to induce two of the characteristic features of the acute inflammatory phases of rheumatoid arthritis: neutrophil accumulation and microvascular plasma protein leakage. In animal models it has been shown that C5a is a potent inducer of inflammatory oedema by a neutrophil dependent mechanism. A striking feature of the acute inflammatory phases of rheumatoid arthritis is the appearance of high numbers of neutrophils in the synovial fluid. It is suggested that C5a might have a role in mediating neutrophil accumulation and, as a consequence, may be important in acute joint swelling and pain. PMID- 2241263 TI - Smoking, lung function, and rheumatoid factors. AB - Positive rheumatoid factor (RF) reactions commonly precede the onset of clinically manifest rheumatoid arthritis (RA). Thus if items associated with RF reactions were traced at the community level this might provide clues to the cause of RA. The relations between smoking and lung functions and the occurrence of RA and RFs in a population sample representative of the adult Finnish population were studied. Rheumatoid factor testing was performed for 7124 subjects (89% of the sample) by the sensitised sheep cell agglutination test. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured with spirometry. 'False positive' RF reactions occurred twice as often in current smokers and ex-smokers than in those who had never smoked. The prevalence of high titres was fourfold greater among current smokers than among those who had never smoked. These associations were statistically significant and independent of age, FVC, and FEV1 in both sexes. The women with airflow limitation (FEV1/FVC less than 70%) had a significantly increased occurrence of RFs which was independent of their smoking history, but no such relationship was found in men. The results suggest an impact of smoking on RF production; a follow up study may show whether the raised RF titers in smokers will be reflected as an increased incidence of RA. PMID- 2241264 TI - Specificity of rheumatoid factors in relation to the disease state in rheumatoid arthritis. AB - Rheumatoid factors found in patients with rheumatoid arthritis react with human IgG and with IgG from some other species. The levels of rheumatoid factor give some indication of prognosis, albeit a rather poor one in this highly variable disease. The high degree of variability may, in part, be due to differences in the fine specificity of the rheumatoid factor in each individual patient, leading to differences in the types of immune complex formed. To study this hypothesis the fine specificity of rheumatoid factors of the IgM, IgA, and IgG classes for IgG from human, baboon, orangutan, macaque, owl monkey, gorilla, marmoset, cow, pig, sheep, goat, horse, mouse, and chicken was examined. Differential reactivity for these species was found and associations between the presence of rheumatoid factor and the development of moderate or severe erosions. PMID- 2241265 TI - Clinical assessment of osteoarthritis of the knee. AB - The repeatability of physical signs used to assess osteoarthritis of the knee has not been systematically examined. The within and between observer variation of 10 commonly used physical signs to determine osteoarthritis of the knee has been assessed here. The results obtained show variation in the repeatability of these signs. For those examining the tibiofemoral joints the repeatability was greater than for those examining the patellofemoral joint. It would therefore seem vital to take note of the repeatability of physical signs in determining the number of subjects to be studied in epidemiological studies and therapeutic studies in osteoarthritis. PMID- 2241266 TI - Do clinical findings associate with radiographic osteoarthritis of the knee? AB - From a population survey of 2865 subjects, test characteristics of a number of clinical findings relating to knee osteoarthritis were calculated against the standard of radiographic diagnosis. The clinical findings included from the history were age, gender, current pain in the knee, swollen knee, pain in both hands, morning stiffness, osteoarthritis in any joint, pain or stiffness, or both, in knees or hips when rising from seated position, and pain in knees or hips while climbing stairs; and from the physical examination: Quetelet's index, Heberden's nodes, bony enlargement, palpable effusion, soft tissue swelling, limitation of knee function, pain with knee flexion, bony tenderness and, finally, the latex fixation test. Of 18 clinical variables, all but Heberden's nodes, palpable knee effusion, pain in both hands, and latex fixation test showed a significant association after adjustment for age. Neither one single variable nor a combination could predict radiographic osteoarthritis of the knee with reasonable accuracy and thus be applicable in clinical practice. The x ray film, therefore, keeps its place in the diagnosis of knee osteoarthritis in general practice as well as in epidemiological research. PMID- 2241267 TI - A prospective study on antiribosomal P proteins in two cases of familial lupus and recurrent psychosis. AB - In two siblings with systemic lupus erythematosus (SLE), who experienced two episodes of psychosis each, a longitudinal study of autoantibodies, including antibodies to ribosomal P proteins, is described. In two of three evaluable periods of 15 weeks antedating psychosis a rise followed by a spontaneous drop in anti-P levels was recorded. In the third period antibodies to ribosomal protein P were absent. It is concluded that results with single samples are not informative, and that frequent measurement of antibodies to ribosomal protein P in patients with SLE may have limited predictive value for psychosis. PMID- 2241268 TI - Stress fractures of the legs and swelling of the ankles in a patient with lupus: a diagnostic dilemma. AB - A patient with systemic lupus erythematosus (lupus) is described, in whom stress fractures of both legs developed, accompanied by swelling of both ankles. The swelling of the right ankle associated with fracture mimicked lupus synovitis, but resolved with healing of the fracture. On the left side the swelling represented true lupus synovitis coexistent with the tibial stress fracture. This presentation posed a diagnostic dilemma. It is necessary to maintain vigilance in the diagnosis of these fractures in lupus. PMID- 2241269 TI - Demonstration of a geode by magnetic resonance imaging: a new light on the cause of juxta-articular bone cysts in rheumatoid arthritis. AB - The magnetic resonance imaging (MRI) features of a rheumatoid arthritic geode are presented. Development of such a cyst from before x ray diagnosis to its coalescence with the wrist joint is described. The evidence suggests that these juxta-articular cysts are not merely an intrusion of the synovial cavity into the bone marrow but start as isolated structures beneath the subchondral bone. PMID- 2241270 TI - Treatment with cimetidine of atypical fasciitis panniculitis syndrome. AB - Three patients presented with septal fasciitis and panniculitis, associated with clinical and laboratory features which precluded straight-forward classification into eosinophilic fasciitis, localised scleroderma, or lupus erythematosus profundus. Treatment with cimetidine caused the remission of cutaneous manifestations and the extracutaneous abnormalities, such as nailfold capillary disturbances and the presence of antithyroid antibodies, improved. It is concluded that features of eosinophilic fasciitis or localised scleroderma and certain additional atypical elements should be categorised as atypical fasciitis panniculitis syndrome. PMID- 2241271 TI - Evans' syndrome associated with dermatomyositis. AB - Autoimmune haematological complications in dermatomyositis are very uncommon. This case report describes autoimmune haemolytic anaemia and thrombocytopenia in a patient with dermatomyositis and pulmonary fibrosis. PMID- 2241272 TI - Comparative study of test kits for measurement of rheumatoid factors by the latex fixation test. AB - The performance of 14 test kits for the measurement of rheumatoid factors by the latex fixation test was investigated; all results were expressed in IU/ml. Reproducibility and properties of control sera were also studied. It was found that half of the kits did not satisfactorily detect rheumatoid factor levels lower than 25 IU/ml. Most kits performed reasonably well in practice. Positive control sera only rarely met strict requirements. The relative costs did not always have a clear correlation with the quality of the results. The variation caused by differences between kits became acceptable when the results were expressed in IU/ml. PMID- 2241273 TI - Management of rheumatoid neck. PMID- 2241275 TI - Negative antineutrophil cytoplasmic antibodies in Behcet's disease. PMID- 2241276 TI - Pregnancy loss, menopause, and the onset of rheumatoid arthritis. PMID- 2241274 TI - Psychological disorders in rheumatoid arthritis: a growing consensus? AB - Previous reviews of psychological factors in arthritis have emphasised the methodological weaknesses of many studies, especially those attempting to measure personality after years of disabling disease. To make sense of the published reports three factors need to be considered separately: previous personality, social stresses, and current mental state. Each can now be measured reliably and independently of symptoms which might be directly attributable to the arthritis. There is a growing consensus that the normal range of personality is represented among patients with early arthritis, that the prevalence of depression is similar to that of patients with other medical conditions, and that social stress is more closely related to depression than activity and the disabling effect of arthritis. Longitudinal studies are now required to examine which social stresses can be attributed to the disabling effect of arthritis. Depression and social stress often manifest themselves to the rheumatologist as excessive complaints of pain and frequent clinic attendances so appropriate psychosocial treatments may reduce this behaviour. PMID- 2241277 TI - Sternoclavicular erosions in polymyalgia rheumatica. PMID- 2241278 TI - Immunological indices of patients with rheumatoid arthritis after methylprednisolone pulse therapy. PMID- 2241279 TI - Response criteria for slow acting antirheumatic drugs. PMID- 2241280 TI - Trauma and seronegative spondyloarthropathy: rapid joint destruction triggered by physical injury in HLA-B7. PMID- 2241281 TI - Rheumatoid arthritis, malignancy, and paraproteins. PMID- 2241282 TI - Concentration and reactivity of the sulphydryl group population on the membrane of intact erythrocytes in patients with rheumatoid arthritis. AB - The sulphydryl population on erythrocyte membrane is shown to vary as a function of the nutritional status of the cell. When an assay based on reaction with Ellman's reagent and controlled conditions were used the mean values (SEM) for the sulphydryl population on the membranes of normal erythrocytes incubated overnight in the presence and absence of glucose were found to be 3.29 (0.27) and 2.56 (0.25) million sulphydryl functions per cell respectively. Under identical conditions rheumatoid erythrocytes incubated in the presence and absence of glucose were found to have a significantly lower sulphydryl population--1.54 (0.08) and 1.15 (0.08) million respectively. The predominant concentrations of sulphydryl groups on the membrane are found at sites on the transmembrane proteins and, in particular, on the hexose transport protein. By influencing the nutritional status of the cells significant differences in activity between the normal and diseased state have been identified and these may have a role in the aetiology of rheumatoid arthritis by altering the response of cells to oxidative stress. PMID- 2241283 TI - Articular cartilage defects of the knee: correlation between magnetic resonance imaging and gross pathology. AB - Magnetic resonance imaging (MRI) of the knee articular cartilage is possible owing to the contrast provided by different signal intensities of adjacent menisci and subchondral bone. The objective of this study was to determine the accuracy of MRI in quantitatively detecting thinning and focal defects of articular cartilage in vivo. High resolution MRI was performed followed by dissection of the knee within one hour of amputations above the knee of eight patients (62-89 years) with peripheral vascular disease. Articular cartilage was examined for erosions, surface irregularities, and appearance. Mean thicknesses of femoral and tibial articular cartilage sagittal sections from MRI were statistically indistinguishable from matched gross thicknesses. In those joints in which cartilage erosions, thinning, or irregularities were detected by MRI the same defects were apparent by gross examination. Cartilage that appeared normal by MRI had a normal gross appearance by gross examination. Thus high resolution MRI can accurately predict gross articular cartilage appearance and thickness, allowing an objective, quantitative, noninvasive assessment of eroded cartilage. PMID- 2241284 TI - Mast cells in the labial salivary glands of patients with Sjogren's syndrome: a histochemical, immunohistochemical, and electron microscopical study. AB - Mast cells in labial salivary glands obtained from patients with xerostomia with or without focal sialadenitis/Sjogren's syndrome were studied. There was no significant correlation between the intensity of local lymphocyte infiltration and the morphometrically analysed number of mast cells staining positive with toluidine blue. Histamine staining with heterologous 11C antiserum showed significantly fewer positive cells than staining with toluidine blue (mean (SD) 62 (10) v 138 (30)). This suggests heterogeneity of the mast cell population. Furthermore, there was a correlation between the focus score and the number of mast cells containing histamine. This suggests that the proliferation of mast cells containing histamine may be locally regulated by the immune inflammation, possibly through mediators from macrophages and fibroblasts. In contrast, the number of mast cells staining positive with toluidine blue could not be used as a marker of the degree of local inflammation. Although transmission electron microscopic analysis did not disclose signs of 'en masse' mast cell degranulation, mast cells may have a role in the local disease process. PMID- 2241285 TI - Juvenile psoriatic arthritis and HLA antigens. AB - The clinical, laboratory, and radiological features, including histocompatibility typing, of 28 patients with juvenile psoriatic arthritis are reported. The most common presentation was that of psoriasis preceding or occurring simultaneously with arthritis. The most common course of juvenile psoriatic arthritis was to start as an oligoarthritis and progress, usually to polyarthritis. No patients with juvenile psoriatic arthritis had uveitis. Overall, most patients had a good outcome (93% in functional class I and II), though 8/28 (29%) did require disease modifying drugs over a mean period of 8.8 years of follow up. The clinical features of these patients were very similar to those of a group of 158 adult patients with psoriatic arthritis with the same disease duration followed up in the clinic. Although there was an increased prevalence of B17 in both juvenile and adult psoriatic arthritis, juvenile psoriatic arthritis showed increased prevalence of A2, whereas adult psoriatic arthritis showed increased prevalence of B27, Bw39, and Cw6. This HLA association differed from that reported in other forms of juvenile arthritis. PMID- 2241286 TI - Significance of low molecular weight C1q in systemic lupus erythematosus. AB - The significance of high serum concentrations of low molecular weight C1q (LMW C1q) in patients with systemic lupus erythematosus (SLE) was studied. Concentrations of LMW-C1q were increased in SLE, but not in rheumatoid arthritis or acute poststreptococcal glomerulonephritis. Concentrations of LMW-C1q in SLE serum samples correlated with titres of anti-dsDNA and were inversely related to concentrations of normal C1q and C3. Serial studies in six patients, who had rising anti-dsDNA titres and who developed a major exacerbation requiring admission to hospital, showed that LMW-C1q increased in parallel with anti-dsDNA, reaching peak values of more than 2000% of normal just before or at the time of clinical relapse and decreasing during convalescence. Most marked increases in LMW-C1q were noted in the three patients in whom C1q concentrations remained normal, whereas increases were less in the three patients who had strongly depressed concentrations of normal C1q. A study of C1q biosynthesis by macrophages cultured from patients with SLE and high serum concentrations of LMW C1q did not show impaired secretion of normal C1q in favour of LMW-C1q, but indicated that serum concentrations of LMW-C1q may reflect the synthetic rate of C1q in vivo. The results show that increased serum concentrations of LMW-C1q may be helpful in diagnosing SLE and suggest that serial determination of LMW-C1q in serum may have predictive value in monitoring patients with SLE. PMID- 2241287 TI - Effect of fibronectin on the Crithidia luciliae test for anti-double-stranded DNA antibodies. AB - The various tests for anti-double-stranded DNA antibodies do not always agree. Plasma fibronectin specifically binds DNA, is a component of immune complexes, and shows variations in concentration with disease activity in systemic lupus erythematosus. It may therefore interfere with the detection of DNA autoantibodies. This possibility was examined in a series of studies using the Crithidia luciliae test. Studies were based on serum samples received during one year (250 samples). Serum samples from 50 patients which were positive or weakly positive in the C luciliae test were used. In blocking experiments fibronectin was added either to the wells or to the serum. In a second series of experiments fibronectin was depleted by affinity chromatography from six serum samples with weak anti-DNA staining. Preincubation of wells with fibronectin or addition of fibronectin to serum invariably blocked the interaction of anti-DNA antibodies with the C luciliae kinetoplast. When fibronectin was removed from serum the intensity of staining was increased. These results indicate that fibronectin influences the detection of anti-double-stranded DNA antibodies using C luciliae and may explain the disparity between the results of different tests for DNA antibodies. Furthermore, the unmasking of positive reactivity when fibronectin is removed from serum has implications for the diagnosis and treatment of systemic lupus erythematosus. PMID- 2241288 TI - Immunogenetic study of the response to streptococcal carbohydrate antigen of the cell wall in rheumatic fever. AB - An immunogenetic study of the response to streptococcal carbohydrate antigen of the cell wall was carried out on members of 15 multiplex families each having more than one sib affected with rheumatic heart disease. They comprised 30 parents and 61 sibs (32 with rheumatic disease and 29 without). Fifty healthy unrelated subjects served as controls. A history was taken and clinical examination carried out. Rheumatic activity was determined and HLA typing was carried out for nine A antigens, 15 B antigens, and six DR antigens. The immune response of lymphocytes to streptococcal polysaccharide antigen of the cell wall of group A beta haemolytic streptococci in vitro was studied by tritiated thymidine uptake. The results were statistically and genetically analysed. It was found that (a) all subjects with rheumatic disease were highly responsive to the streptococcal polysaccharide antigen of the cell wall, the sib pairs being mostly HLA identical; (b) all low responders had no rheumatic disease and their phenotypes were mostly different from those of the rheumatic member of their sib pair; (c) correlation of immune responsiveness (high or low) between HLA identical sibs was significant, but insignificant between haplotype identical and non-identical sibs; (d) the gene responsible for high responsiveness to the streptococcal polysaccharide antigen of the cell wall is recessive and closely linked to HLA. In conclusion, it was found that exposure to pharyngeal infection with group A beta haemolytic streptococci may lead to acute rheumatic fever in those with an inherited recessive gene responsible for high responsiveness to the streptococcal polysaccharide antigen of the cell wall. PMID- 2241289 TI - Clinical and laboratory studies in patients with leprosy and enthesitis. AB - In a combined clinical, radiological, and laboratory study of 77 patients throughout the leprosy spectrum, 10 patients had an enthesitis which has not been described previously as far as is known and which was not associated with the characteristics of erythema nodosum leprosum reactions. C reactive protein and alpha 1 acid glycoprotein values were significantly lowered only in those patients with leprosy and enthesitis. No radiological abnormalities were found. PMID- 2241290 TI - Arthritis in a human T lymphotropic virus type I (HTLV-I) carrier. AB - The case is described of a 57 year old woman with polyarthritis fulfilling the 1987 revised criteria of the American Rheumatism Association for rheumatoid arthritis, accompanied by clinical carrier state infection of HTLV-I. Anti-HTLV-I IgM antibodies were detected by western blot analysis in her synovial fluid and serum. Atypical lymphocytes with nuclear convolutions were found in synovial fluid and synovial tissue obtained from the affected knee joint, suggesting in situ activation of HTLV-I infected lymphocytes in the affected synovial compartment. The HTLV-I antigens were detected (1.2%) in short term cultured synovial fluid lymphocytes, by indirect immunofluorescence. These findings supported the possibility that HTLV-I has a role in triggering or modifying inflammation in the synovial compartment. PMID- 2241291 TI - Lymphoedema of the limbs as an extra-articular feature of rheumatoid arthritis. AB - Seven patients with lymphoedema of the hands and arms, an unusual extra-articular feature of rheumatoid arthritis, are described. In all cases the lymphoedema persisted throughout follow up--in one case for more than five years--and was resistant to treatment with slow acting drugs, steroids, or cytotoxic agents. There was no correlation with severity of disease. It is concluded that the lymphoedema in these patients may be associated with reduced numbers of lymphatic vessels; increased capillary permeability or abnormal fibrinolysis may also be contributory factors. Conservative management of such patients is recommended. PMID- 2241292 TI - Antiproteinuric effect of captopril in a patient with lupus nephritis and intractable nephrotic syndrome. AB - A 22 year old woman presented with lupus nephritis, hypertension, and intractable nephrotic syndrome. Albumin and furosemide given intravenously was ineffective. Captopril administered in a daily dose of 62.5 mg was associated with a reduction in proteinuria from 28 g/24 hours to 11.5 g/24 hours over 10 weeks, resulting in a weight reduction of 16 kg. This was achieved with relative preservation of renal function. Captopril should be considered in the treatment of intractable proteinuria in patients with lupus nephritis, or when cytotoxic drugs are refused, because of its efficacy and relative safety. Captopril should, however, be used as an adjunct and not as a substitute for standard treatment. PMID- 2241293 TI - Simultaneous presentation of upper lobe fibrobullous disease and spinal pseudarthrosis in a patient with ankylosing spondylitis. AB - A 51 year old man with a 20 year history of ankylosing spondylitis and pronounced thoracic gibbus presented with two simultaneous complications of longstanding ankylosing spondylitis, upper lobe fibrobullous disease, and spinal pseudarthrosis. No neurological sequelae developed and treatment was conservative. Both these lesions mimic tuberculosis, and so it is important to determine them accurately to avoid unnecessary antituberculosis treatment. Both of these complications are reported to occur in longstanding ankylosing spondylitis and their simultaneous presentation may be more common than is realised. This case is believed to be the first such report of their association. PMID- 2241294 TI - Avascular necrosis of the femoral head presenting as trochanteric bursitis. AB - Five patients are described with avascular necrosis of the femoral head who presented with ipsilateral trochanteric bursitis, in the absence of clearcut hip joint disease. Avascular necrosis was indicated by magnetic resonance imaging. It is suggested that clinical trochanteric bursitis, especially when refractory to local corticosteroid treatment, may be the initial sign of hip disease. In the patient with risk factor(s) for avascular necrosis that diagnosis should be considered and evaluated with appropriate studies, such as magnetic resonance imaging, to prevent weight bearing at an early stage and permit possible surgical decompression in the hope of postponing or obviating the need for total hip replacement. PMID- 2241295 TI - First two decades of British rheumatology: a personal perspective. PMID- 2241296 TI - Systemic sclerosis: is there a treatment yet? PMID- 2241297 TI - Surgery of the rheumatoid shoulder. PMID- 2241298 TI - Surgery of the rheumatoid knee. PMID- 2241299 TI - Rheumatoid arthritis and ankle surgery. PMID- 2241300 TI - Surgery of the rheumatoid cervical spine. PMID- 2241301 TI - The rheumatoid foot: a sideways look. PMID- 2241302 TI - Surgical treatment of the rheumatoid hip. PMID- 2241303 TI - Surgery for the rheumatoid wrist and hand. PMID- 2241304 TI - Surgery of the rheumatoid elbow. AB - I suggest that for too long the problem of the rheumatoid elbow, particularly the need for surgical intervention, has been underestimated. Where the latter has been advocated the philosophy has been adopted that synovectomy and debridement with excision of the head of the radius is probably all that is required, or that in the late case excision arthroplasty may yield an adequate result. I suggest that these approaches are no longer tenable. Synovectomy and debridement with or without excision of the head of the radius does indeed retain an extremely valuable place in the management of stage 1, 2, and early stage 3 disease. In the later stages of the disease, however, serious consideration must now be given to total joint replacement, the results of which can be remarkably successful and durable, and the complications from which can now be contained within acceptable limits provided that the operating team is fully experienced. It must also be stressed how necessary it is in the medical or combined clinic to pursue careful clinical and radiological monitoring of the rheumatoid elbow so that signs of dangerous deterioration can be recognised early, and surgery applied at a time when optimal conditions for the particular surgical weapons to be used still exist. PMID- 2241305 TI - [Current possibilities in the control of Loa Loa filariasis]. AB - Loa loa is currently considered as a major pathogen in man. The clinical repercussions of this filariasis have been clearly established and treatment is considered essential. Ivermectin, administered alone or with diethylcarbamazine presents interesting therapeutic possibilities. The review of vector control methods show that trapping is the only effective measure of protection. In order to reduce the endemicity of loaiasis, mass treatment with ivermectin could be envisaged immediately. However, the development of this filariasis is directly related to the development of the Central African forest region. PMID- 2241306 TI - [Epidemiological status of onchocerciasis in the Congo]. AB - Analysis of 25 surveys carried out in the Congo between 1978 and 1987 (covering nine of the ten administrative regions), during which 6,215 subjects were examined, showed that onchocerciasis is endemic in the southern part of the country. Two main foci meeting at the southern exit of Brazzaville (Pool region) were identified. One focus in the Djoue basin. The other is the zone along the Congo river stretching from below Brazzaville south west to the Zaire border. Two secondary foci were noted, one in the region of the Bouenza and the other west of the Mayombe mountains. Surveys carried out in the north of the country and in the west did not reveal any onchocerciasis. However, certain areas of primary forest in these regions were found to be endemic for Mansonella streptocerca. Simulium damnosum s.l. in the sole vector of onchocerciasis. In both the Pool foci, and in the Mayombe focus, prevalences assessed from microfilarial and cyst counts were high but the mean microfilarial densities were relatively low. In certain villages over 90% of the population aged over 14 years may present with microfilariae and nearly 70% may present cysts. PMID- 2241307 TI - [Study of the transmission of onchocerciasis in the surroundings of a refugee camp located in the savanna zone of Cameroon]. AB - Chadian refugees, most of whom are free from onchocerciasis, settled recently in a camp in a savanna area of the northern Cameroon where the prevalence is about 80% and the blindness rate is 4% of the adult population. In view of the risks of onchocerciasis facing the immigrants, the authors carried out an entomological survey in this region aimed at determining the modes of transmission and assessing the possibilities for the control of this disease. After a three-month survey in the study area, it appears clearly that 1) transmission takes place only during the rainy season, 2) the main vectors are the two savanna species, Simulium damnosum s.s. and Simulium sirbanum, 3) the larval breeding sites are not located on the principal river, the Faro, but on its small seasonal tributaries, 4) the local populations still free from onchocerciasis and the Chadian refugees who farm close to these tributaries run the risk of getting serious ocular lesions in the long run which could lead to blindness. The conclusions of this survey prompted the authors to envisage an onchocerciasis control campaign in this area against the larval stages of the vectors. PMID- 2241308 TI - [Helminths of domestic pork in Ituri, Upper Zaire]. AB - In Ituri (Upper-Zaire) pig farming is extensively and traditionally managed, animals wandering about in the villages and neighbouring fields. Helminths of the gastrointestinal tract most commonly encountered are Oesophagostomum sp. Hyostrongylus rubidus, Globocephalus urosubulatus and Ascarops strongylina. Parasitic burdens are low and gross lesions not frequently seen except nodules of oesophagostomiasis. Infections with Metastrongylus salmi and Metastrongylus pudendoctus have a very high prevalence (between 64 and 86%) causing gross lesions of pneumonia on the diaphragmatic lobes. The present socio-economic pattern of pig production in Ituri doesn't allow hardly to plan a rational control of helminth disease by use of drugs. Hydatidosis (Echinococcus granulosus) seeming to be absent in this area of Zaire, the only serious helminthic zoonosis we have to take into account is cysticercosis due to Cysticercus cellulosae. Its very high endemicity (between 10 and 30%) will have to lead the veterinary service to improve the search and destruction of infected carcasses. PMID- 2241309 TI - [Sexually transmitted diseases in the female population of Pikine, Senegal]. AB - The prevalence of some sexually transmitted disease is determined in 250 gynaecology patients and in 200 pregnant women seen in primary health centers in Pikine, Senegal. The main reason for consultation at gynaecology is infertility. Gonorrhoea and Chlamydia trachomatis infection are present respectively in 1.5% and 7% of pregnant women and in 4.4% and 7.6% of gynaecology patients. Human papillomavirus infection, determined by DNA extraction and hybridization technique, is seen in 4% of obstetric and in 1.2% of gynecology patients. Cytological anomalies is found in 5.5% of pregnant women and in 4.8% of gynecology patients. PMID- 2241310 TI - From monitoring to predicting outcome. PMID- 2241311 TI - The acutely affected abdomen in paraplegic spinal cord injury patients. AB - The records of 145 paraplegic or quadriplegic patients were reviewed to identify those factors useful in the correct diagnosis of the acute abdomen in this population. Twenty-one patients had 22 episodes of acute or subacute abdominal problems. Presenting complaints, physical findings, and laboratory results were useful in various ways. However appropriate radiographic studies led to the correct diagnosis in 77% of patients. Although paraplegic and quadriplegic patients are predisposed to a distinct constellation of medical problems, including urinary tract infection and calculi, they also may present with other abdominal conditions that cause significant morbidity and mortality if not promptly recognized. PMID- 2241312 TI - Intraoperative blood pressure. What patterns identify patients at risk for postoperative complications? AB - While monitoring blood pressure is a routine part of intraoperative management, several methods have been proposed to characterize intraoperative hemodynamic patterns as predictors of postoperative complications. In this prospective study of a high-risk population of hypertensive and diabetic patients undergoing elective noncardiac surgery, one objective was to compare different approaches to the assessment of intraoperative hemodynamic patterns to identify those patterns most likely to be associated with postoperative complications. Twenty-one per cent of the 254 patients sustained cardiac or renal complications after operation. Patients with more than 1 hour of greater than or equal to 20-mmHg decreases in mean arterial pressure (MAP) or patients with less than 1 hour of greater than or equal to 20-mmHg decreases and more than 15 minutes of greater than or equal to 20-mmHg increases were at highest risk for postoperative complications. Together these two patterns had a 46% sensitivity rate and a 70% specificity rate in predicting postoperative complications. Using 20% change in intraoperative MAP produced results nearly identical to 20-mmHg changes. When the duration of 20-mmHg changes was accounted for, changes of a greater magnitude (e.g., 40 mmHg) were not significant independent predictors of complications. The use of the mean difference from preoperative MAP was misleading because patients who experienced both high and low MAPs tended to have nearly normal mean MAPs, but high complication rates. The absolute magnitude of intraoperative MAPs, regardless of the preoperative levels, also was evaluated. The overall mean intraoperative MAP was not a significant predictor of complications. Specific intraoperative MAPs (e.g., less than 70 mmHg and more than 120 mmHg) also were evaluated. While neither was a significant predictor, there was a trend for increased complications among patients whose MAPs decreased to less than 70 mmHg. Intraoperative blood pressure should be analyzed in relation to the patient's preoperative blood pressure. Prolonged changes of more than 20 mmHg or 20% in relation to preoperative levels were significantly related to complications. PMID- 2241315 TI - Parietal cell vagotomy and dilatation for peptic duodenal stricture. AB - Gastric outlet obstruction due to peptic duodenal stricture (pyloric stenosis) was treated with parietal cell vagotomy and dilatation of the stricture in 32 patients. Follow-up is in the range of 5 years in 37.4% of the patients, while 6 to 10 years follow-up is available in 62.4% of the patients. At their last follow up, 74.9% of the patients were in either Visick 1 or 2 clinical status. Recurrence rates have been 3.1% at 1 year, 9.3% at 5 years, and 21.8% after 6 to 10 years follow-up. There has been only one instance (3.1%) of restenosis. Two patients required reoperation because of recurrence and one of them died. PMID- 2241314 TI - Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far-advanced gastric cancer. AB - To evaluate the clinical efficacy of intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer, particularly with peritoneal seeding, we investigated the survival times of 59 patients who underwent distal subtotal gastrectomy, total gastrectomy, or total gastrectomy combined with concomitant resection of some of the remaining intra-abdominal organs. In all the 30 patients given IPHP, no cancer cells were present posthyperthermically in the lavage from the Douglas pouch. The 30 patients given IPHP lived longer than the 29 patients not given IPHP (p = 0.001), with a 1-year survival rate of 80.4% in the former group compared to 34.2% in the latter. With respect to a comparison of survival time of patients with peritoneal seeding, 7 patients not given IPHP had a 6-month survival rate of 57.1% and did not survive more than 9 months, whereas 20 patients given IPHP had 1- and 2-year survival rates of 78.7% and 45.0%, respectively; here the difference was significant (p = 0.001). The IPHP and control groups without peritoneal metastasis included 10 and 22 patients, respectively, and the 1-year survival rates are 85.4% and 45.3%, respectively. The survival rates of the former exceeded those of the latter, with p = 0.015 by the generalized Wilcoxon test. Thus this combined therapy offers the promise of extended survival for patients with far-advanced gastric cancer. PMID- 2241313 TI - Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections. AB - We designed a multicenter study to compare tobramycin/clindamycin to imipenem/cilastatin for intra-abdominal infections. We included the Acute Physiology and Chronic Health Evaluation (APACHE II) index of severity and excluded patients without established infection. Two hundred ninety patients were enrolled, of whom 162 were evaluable. Using logistic regression to analyze both outcome at the abdominal site of infection and outcome as mortality, we found a significant correlation for both with APACHE II score (p less than 0.0001 for both). Next we analyzed the residual effect of treatment assignment and found a significant improvement in outcome for imipenem/cilastatin-treated patients (p = 0.043). The differences in outcome were explained by a higher failure rate for patients with gram-negative organisms for tobramycin/clindamycin-treated patients (p = 0.018). This was reflected in a significantly higher incidence of fasciitis requiring reoperation and prosthetic fascial replacement. Maximum peak tobramycin levels were analyzed for 63 tobramycin/clindamycin patients harboring gram negative organisms. For failures the maximum peak was 6.4 +/- 1.9 micrograms/mL, and time to maximum peak was 4.6 +/- 5.2 days. For successes the maximum peak was 6.1 +/- 1.7 micrograms/mL, occurring at 3.8 +/- 2.6 days. This study supports inclusion of severity scoring in statistical analyses of outcome results and supports the notion that imipenem/cilastatin therapy improves outcome at the intra-abdominal site of infection as compared to a conventionally prescribed amino-glycoside-based regimen. PMID- 2241316 TI - Intrarectal ultrasonography in rectal cancer staging and in the evaluation of pelvic disease. Clinical uses of intrarectal ultrasound. AB - Accurate preoperative staging of a rectal cancer patient may impact heavily on subsequent management. This study attempts to evaluate the accuracy of intrarectal ultrasonography (IRUS) in staging rectal cancers compared to clinical and pathologic examination. In addition the accuracy of IRUS was assessed in a group of patients with uncertain pelvic-perirectal disease after a negative physical examination. In a prospective manner, 52 cancer patients were staged with digital exam and IRUS. Accuracy rates were 48% and 83%, respectively, compared to pathologic evaluation in assessing wall penetration, and IRUS identified positive lymph nodes in 12 of 17 cases. In patients with pelvic disease, IRUS corresponded with pathologic diagnosis in 15 of 17 cases and revealed new information in 6 patients. Intrarectal ultrasonography appears to be the most accurate imaging technique for staging rectal cancers and demonstrates promise in the evaluation of perirectal-pelvic disease. PMID- 2241317 TI - Localization and peptide content of endocrine pancreatic tumors. AB - Endocrine pancreatic tumors contain and frequently secret neurohormonal peptides. This phenomenon can be used as a diagnostic and classifying tool. This study analyzes 31 patients operated on because of an endocrine pancreatic tumor, including the diagnostic procedures and the localization methods. In 15 insulinoma cases only 6 patients had a positive arteriography, while all 11 selective pancreatic vein samplings were positive. The immunoreactivity showed that, besides insulin, most tumors also contained other peptides. Of four gastrinoma cases the arteriography was positive in three, but the selective vein sampling localized the tumor in all. The tumor's content of peptides showed mixed patterns. In the four glucagonomas, the arteriography was positive in all and the venous sampling performed in three of the cases also was positive. In five pancreatic polypeptide-containing tumors (PP-omas) the arteriography was positive in four and sampling performed in two was positive in both. In the PP-omas the peptide pattern showed that these tumors frequently contain several peptides. We used selective pancreatic vein sampling in 21 cases with positive result in all. In the cases in which arteriography was negative, the sampling results helped the surgeon to find the tumor. The peptide pattern in the tumors varied greatly and most tumors were multihormonal. PMID- 2241318 TI - Localization and surgical treatment of occult insulinomas. AB - Management of patients with biochemical evidence of insulinoma and negative preoperative imaging studies (occult) tumors is controversial, varying from primarily medical management to aggressive, blind nearly total pancreatectomy to extirpate the tumor. Since 1982, 12 consecutive patients with occult insulinoma underwent preoperative portal venous sampling (PVS) for insulin followed by surgical exploration with intraoperative ultrasound (IOUS). Eleven of twelve patients (92%) had insulinoma removed and were cured. Portal venous sampling correctly predicted the location of the insulinoma in 9 patients (75%) and that no tumor would be found in another patient. A fourfold insulin gradient in the pancreatic tail of one patient correctly predicted that a distal pancreatectomy would remove the insulinoma despite the fact that neither palpation nor IOUS identified any tumor. Intraoperative ultrasound was the single best method to identify occult tumors because it correctly identified 10 of 11 insulinomas that were found, including five pancreatic head tumors that were not palpable. Palpation identified five insulinomas. Of the 10 tumors that were identified during operation by palpation or ultrasound, IOUS identified significantly more (100% versus 50%, p = 0.03) and guided the successful enucleation of each. The results support the strategy of preoperative PVS and operation with IOUS to localize and remove insulinoma in patients with occult tumors. Most tumors (75%) will be correctly localized to a specific pancreatic region by preoperative PVS and identified by IOUS (83%), allowing simple enucleation and biochemical correction of hypoglycemia. Morbid blind pancreatic resections are no longer indicated and long-term medical management of hypoglycemia should be reserved for the occasional patient (8%) who fails preoperative PVS and operation guided by IOUS. PMID- 2241319 TI - Does carotid restenosis predict an increased risk of late symptoms, stroke, or death? AB - The identification of carotid restenosis as an unexpected late complication of carotid endarterectomy has prompted concerns regarding its importance as a source of new cerebral symptoms, stroke, and death. To investigate these concerns, we analyzed a consecutive series of 507 patients undergoing 566 carotid endarterectomies, each documented as technically satisfactory. Post-operative duplex Doppler examination data at 3 days, 1, 3, 6, 12 months, and annually thereafter in 484 arteries (85.5%) permitted classification of these arteries according to the most severe degree of postoperative stenosis: normal (n = 306); 1% to 19% (n = 89); 20% to 50% (n = 40); more than 50% (n = 49, including 8 occluded). The incidence of more than 50% restenosis was 14.5% in female and 7.7% in male patients (p = 0.003). Life table analyses to 10 years revealed a significantly greater life expectancy among those with restenosis (p = 0.05). Stroke was also less likely in patients with restenosis, although this difference did not reach statistical significance. When survival and stroke were both endpoints, the likelihood of patients with more than 50% restenosis remaining alive and stroke free was also greater than the less than 20% stenotic group (p = 0.03). Thus patients with carotid restenosis were less likely than patients with normal postoperative scans to have late symptoms, stroke, or early death. PMID- 2241320 TI - Anorectal carcinoid tumors: is aggressive surgery warranted? PMID- 2241321 TI - Risks of incidental cholecystectomy. PMID- 2241322 TI - Difficulties encountered in the treatment of patients who develop sepsis after esophageal perforation. PMID- 2241323 TI - Surgical management of chronic empyema: the role of thoracoplasty. PMID- 2241324 TI - Behavior of small bronchial carcinomas. PMID- 2241325 TI - Choreoathetosis as a complication of cardiopulmonary bypass. PMID- 2241326 TI - Thoracoplasty: current application to the infected pleural space. AB - Thoracoplasty, once commonly used in the management of cavitary pulmonary disease, continues to find application in the obliteration of infected pleural spaces. This study reports a series of 13 patients receiving thoracoplasty between 1976 and 1989. Five patients had chronic apical empyema spaces without prior resection of lung tissue. Two of the empyemas were due to tuberculosis, two were due to atypical mycobacteria, and one was due to postpneumonic empyema. All patients had extensive destruction of upper lobe tissue. Eight patients had undergone prior pulmonary resection; 3 had persistent infected spaces in the early postoperative period, 3 had development of empyemas and bronchopleural fistulas late (5 to 19 years) after pulmonary resection, and 2 had postpneumonectomy empyema. All patients had rigid cavity walls preventing space obliteration by rib removal alone and required concomitant resection of the thickened pleura and intercostal muscle tissues. Bronchopleural fistulas were present in 11 patients and were closed with adjacent nonintercostal muscle. All patients survived and had successful obliteration of the infected spaces with acceptable physiological and cosmetic results. We conclude that thoracoplasty remains a useful procedure in the management of the infected pleural space in select patients. PMID- 2241327 TI - Repair of supravalvar aortic stenosis: cardiovascular morphometric and hemodynamic results. AB - Supravalvar aortic stenosis is associated with normal systolic pressure in the aorta and its branches with the singular exception of the coronary arteries, which are hypertensive. This uncommon lesion has been treated by patch aortoplasty of several types. We examined hemodynamics and morphometrics in 13 patients who underwent operation for supravalvar aortic stenosis from 1979 through 1988. They ranged in age from 2 to 43 years (mean age, 14.5 +/- 3.8 years [+/- standard error of the mean]). There were no operative deaths. Preoperative and postoperative (1 to 5 years) catheterization or echocardiography or a combination of these was done in all but 3 patients (1 died late suddenly without a postmortem examination; 1 was lost to follow-up; and 1 has not yet been restudied). Pressure gradients across the stenosis in patients treated with a single-sinus patch (n = 4) were 65 +/- 18 mm Hg preoperatively and 5 +/- 3 mm Hg postoperatively (p less than 0.05) and in patients with a bisinus patch (n = 6), 83 +/- 15 mm Hg preoperatively and 6 +/- 2 mm Hg postoperatively (p less than 0.05); the two groups were not significantly different. Measurements of the diameters of the coronary arteries, aortic annulus, and descending aorta were made, and calculation of the ratio of the coronary artery and annulus diameters to the descending aortic diameters both preoperatively and postoperatively was possible in 5 patients. The left coronary artery was larger than normal before and after operation. Preoperatively there was a disproportionate increase in left coronary artery and annulus size during systole. Left ventricular wall thickness decreased significantly postoperatively (p less than 0.05). Repair of supravalvar aortic stenosis (localized and diffuse) by both single sinus and bisinus patch repair is safe and hemodynamic results are good.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241328 TI - Strategy for lymphadenectomy in lung cancer three centimeters or less in diameter. AB - We have surgically treated 221 patients with a primary lung cancer 3.0 cm or less in diameter. There were 8 patients with a tumor 1.0 cm or less in diameter (group A), 84 with a tumor 1.1 to 2.0 cm in diameter (group B), and 129 with a tumor 2.1 to 3.0 cm in diameter (group C). The incidence of N0, N1, and N2 disease was 100%, 0%, and 0%, respectively, for patients in group A; 83%, 5%, and 12% in group B; and 62%, 12%, and 25% in group C (N0 versus N2, p less than 0.01). For the 63 patients with regional lymph node involvement, "skipping" metastasis was present in 28.6%. The 5-year survival rate was 80% for group A, 74% for group B, and 51% for group C (group B versus group C, p less than 0.01). Of the 121 patients who underwent complete resection and were followed up for 5 years, 41% had recurrence, 8% with local recurrence and 33% with distant metastasis. Therefore, it is important to do as complete a resection as possible together with mediastinal lymphadenectomy. Efforts to detect systemic spread should be made at the time of preoperative evaluation, even when the lung tumor is small. PMID- 2241329 TI - Choreoathetosis after deep hypothermia without circulatory arrest. AB - In 8 of 758 patients undergoing an intracardiac operation under cardiopulmonary bypass and hypothermia, choreoathetosis developed 3 to 7 days postoperatively. Before the onset of choreoathetosis, varying degrees of neurological dysfunction were noted. Electroencephalography and neuroimaging failed to detect any responsible functional or structural changes. Six patients are alive 1 to 3 years postoperatively, and their condition is improving. Two patients died of aspiration or sepsis. All patients were grouped based on factors identified as being possibly causative: depth of hypothermia, cooling time, flow rate, and repeated hypothermia. The incidence of choreoathetosis was significantly different in group A (rectal temperature greater than 25 degrees C) compared with group B (rectal temperature less than or equal to 25 degrees C) (0/295 versus 8/463; p = 0.02). Based on cooling time, the incidence of choreoathetosis was significantly different in group B1 (cooling time less than 1 hour) compared with group B2 (cooling time greater than or equal to 1 hour) (1/220 versus 7/243; p = 0.05). Based on flow rate during cooling, group B2 was further divided into the low-flow group (less than 1,500 mL.min-1.m-2) and the high-flow group (greater than or equal to 1,500 mL.min-1.m-2). Although not significant, the incidence of choreoathetosis was higher in the high-flow group (6/153 versus 1/90; p = 0.22). In group B patients having reoperation, the incidence of choreoathetosis was higher than in patients operated on for the first time (5/54 versus 3/409; p less than or equal to 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241330 TI - Prognostic determinants in extracorporeal membrane oxygenation for respiratory failure in newborns. AB - Extracorporeal membrane oxygenation (ECMO) is becoming an accepted therapeutic modality for newborn respiratory failure, but there is little information available regarding the prognostic determinants with this technique. One hundred thirty-five newborns treated with ECMO over a 4-year period were critically analyzed with regard to the influence that birth weight, gestational age, age at initiation of ECMO, best blood gases before ECMO, number of hours on ECMO, renal failure, intracerebral hemorrhage, and long-distance air transport had on survival. Infants with meconium aspiration and those undergoing long-distance transfer showed significant differences in blood gases before ECMO, with survivors having more normal pH and carbon dioxide tension values. Intracerebral hemorrhage and renal failure that developed during ECMO were grave prognostic signs, with few survivors in either group. These data show that ability to ventilate patients before ECMO, giving normal carbon dioxide tension and pH values, is an important prognostic sign in infants with meconium aspiration and undergoing long-distance transfer for ECMO, whereas renal failure and intracerebral hemorrhage are usually lethal complications of ECMO. Each center performing ECMO should continually reevaluate this invasive technique and its results and complications. PMID- 2241331 TI - Acquired benign esophagorespiratory fistula: report of 16 consecutive cases. AB - Sixteen cases of acquired benign esophagorespiratory fistula were treated in a 20 year period. A delay in diagnosis was usual, and most patients were first seen with a pulmonary infection already developed. Contrast esophageal x-ray studies established the diagnosis in all patients. There were seven esophagotracheal and nine esophagobronchial fistulas. A fistula between the esophageal diverticulum and a bronchus considered to be of inflammatory origin developed in 7 patients. A fistula as the consequence of trauma developed in 9 patients, and these fistulas were situated at a higher level of the respiratory tree. All patients underwent surgical treatment; in 12 it was definitive, and in 4 temporary gastrostomy was performed to improve nutrition before definite repair. The definitive repair consisted of eventual diverticulectomy, division of the fistula, and suture of both esophageal and respiratory defects. Two patients required esophageal resection and later reconstruction with colon interposition. One patient died, creating an operative mortality of 8.3% in the definitive-repair group. The remaining 11 patients had a gratifying long-term result. There were two deaths in the gastrostomy group due to an extremely poor condition of patients and debilitating pulmonary infection. Early diagnosis of this rare condition is necessary if severe pulmonary complications are to be avoided. Early direct repair gives excellent results. PMID- 2241332 TI - Correction of truncus arteriosus with truncal valvar stenosis or insufficiency using two homografts. AB - Surgical correction of truncus arteriosus requires the creation of right ventricular to pulmonary artery continuity and closure of the ventricular septal defect. A variety of conduits have been used including valved and nonvalved. Despite a significant incidence of truncal valvar stenosis and insufficiency, this valve has seldom been replaced. We present 4 cases of truncus arteriosus with truncal valvar stenosis or insufficiency that were repaired using two valved homografts: one to create the pulmonary outflow tract and the other to replace the abnormal truncal valve. Two of these patients are doing well after 4 months. Another child survived the operation and did well for 2 months when she died suddenly. The last child died 14 hours postoperatively from low cardiac output syndrome secondary to diabetic hypertrophic cardiomyopathy. When truncal valvar abnormalities are present, the primary repair of truncus arteriosus in an infant should include replacement of the truncal valve. Total correction can be successfully achieved using two valved homografts, resulting in long-term palliation and freedom from thromboembolic events and the use of anticoagulants. PMID- 2241333 TI - Influence of prosthetic design on durability of the Liotta porcine valve in the mitral position. AB - From March 1979 to December 1984, the Liotta low-profile porcine bioprosthesis was employed for mitral valve replacement in 71 patients to avoid potential left ventricle-prosthesis mismatch occasionally observed with the standard, high profile, Hancock porcine xenograft. Follow-up of 61 operative survivors showed at 10 years an actuarial survival of 67% +/- 7%, freedom from thromboemboli of 96% +/- 2%, freedom from structural deterioration of 63% +/- 11% and freedom from all Liotta bioprosthesis-related complications of 53% +/- 10%. Complications related to excessive protrusion of the stent into the left ventricular cavity were eliminated with the Liotta bioprosthesis; the peculiar stent configuration, however, was responsible for an increased rate of structural deterioration requiring reoperation in 10 patients (2.8% +/- 0.9%/patient-year) at a mean interval of 76 +/- 18 months after mitral valve replacement (range, 45 to 106 months). Common findings in all explants were cusp prolapse, cusp tears, and commissural rupture related to various degrees of tissue calcification, constantly leading to severe prosthetic incompetence. As also shown experimentally, such structural changes have been attributed to increased systolic stresses on the closed cusps, favored by excessive reduction of the stent height. Our experience shows that the Liotta bioprosthesis used for mitral valve replacement does not provide any clear-cut advantage over standard porcine bioprostheses and that its long-term durability appears affected by the unique prosthetic design. PMID- 2241334 TI - Surgical management of pulmonary metastatic leiomyosarcoma with gross endobronchial extension. AB - Metastatic leiomyosarcoma occasionally is seen with gross endobronchial extension without invasion of the bronchial wall. These patients have major airway obstruction and partial or total atelectasis of the lung. Precise bronchoscopic assessment coupled with intraoperative bronchotomy allows the surgeon to determine the origin of the tumor and to save uninvolved pulmonary parenchyma. Our experience with 4 such patients illustrates the possibility of saving lung tissue despite total bronchial obstruction. PMID- 2241335 TI - Clinical performance of St. Jude and Medtronic-Hall prostheses: a randomized comparative study. AB - Newer and improved models of mechanical prostheses are regularly added to surgeons' armamentarium. This study was designed to compare the clinical performance of two of the most used current models of mechanical prostheses. From August 1983 through July 1985, 182 white patients were prospectively randomized to implantation of the St. Jude Medical (95 patients) or Medtronic-Hall (87 patients) prostheses. There were 84 mitral, 85 aortic, and 13 double (mitral and aortic) valve replacements. There were no differences between the two groups with regard to sex distribution, age, functional class, emergency operation, and site of implantation. Early mortality was 3.2% for patients with the St. Jude valve and 5.7% for those with the Medtronic-Hall (p = NS). The survivors were followed for 3 to 5 years (mean, 4.2 +/- 0.6 years; cumulative follow-up, 559 patient years). Late mortality was 7.1%/patient-year for the St. Jude group and 3.2%/patient-year for the Medtronic-Hall group (p less than 0.05). However, the valve-related mortality was equal (1.4%/patient-year) for both groups. Noncardiac causes accounted for most of the difference between the St. Jude and Medtronic Hall groups (2.5%/patient-year and 0.4%/patient-year, respectively). There were no cases of thrombotic obstruction, whereas serious systemic thromboembolism occurred at the rate of 1.8%/patient-year (5 episodes) for the St. Jude group and 2.5%/patient-year (7 episodes) for the Medtronic-Hall group (p = not significant); there were another nine episodes of systemic embolism that left no sequelae. Three patients (St. Jude, 2; Medtronic-Hall, 1), all of whom had aortic valve replacement, required reoperation (0.5%/patient-year) because of prosthetic endocarditis, with two deaths.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241336 TI - Clinical experience with the Medtronic-Hall valve prosthesis. AB - Medtronic-Hall valves were implanted during 204 procedures performed between 1982 and 1988. Mean population age was 54.4 years; 96% of patients were in New York Heart Association functional class III or greater. Emergency operations constituted 16% of the procedures. Rheumatic heart disease was the single most common indication for valve replacement. In 18% of patients, operation was performed to replace a previous prosthetic valve. The mean follow-up was 3.2 years. Overall operative mortality was 10.3%, the highest mortality being for double-valve replacements (24%). Valve-related mortality, by position, was 5.3% for aortic valves, 6.0% for mitral valves, and 4.0% for multiple-valve replacements. Actuarial 5-year freedom from events were: survival, 68%; thromboembolism, 90%; prosthetic valve endocarditis, 98%; paravalvular leak, 95%; and reoperation, 92%. Complications with the highest mortality were thromboembolism (36%) and endocarditis (33%). The complication rates in this series are high but the patients were more severely ill than in other reports, and operative survivors experienced a considerable improvement in New York Heart Association functional class. PMID- 2241337 TI - Giant chest wall tumor resulting from tissue reaction to foreign bodies. AB - Three patients are reported in whom chest wall tumors developed 19 to 28 years after thoracoplasty and increased in size with time. The tumors could be removed operatively with good results. All tumors were composed of hematoma and necrotic material, and in all cases they revealed foreign bodies microscopically. Diagnosis and possible etiological factors are discussed. PMID- 2241338 TI - Air contamination in open heart surgery with disposable coveralls, gowns, and drapes. AB - The effect of a polypropylene coverall, replacing shirt and trousers, combined with sterile laminated gowns and drapes compared with an all-cotton system was studied in regard to the dispersion of bacteria and particles in a conventionally ventilated operating theater. The operations carried out were open heart procedures in 30 adult patients. Blood agar sedimentation plates were placed in the operative, anesthesia, and perfusion areas. The mean sedimentation values during 1 hour after the start of operation were as follows in the laminate group: 63 colony-forming units (cfu)/m2 in the operative area; 77 cfu/m2 in the anesthesia area; and 143 cfu/m2 in the perfusion area. The corresponding figures in the cotton group were 350 cfu/m2, 364 cfu/m2, and 437 cfu/m2, respectively (p less than 0.0002). At the beginning of the operation, the mean values noted for colony-forming units in the air at the operative site were 8.0 cfu/m3 in the laminate group and 31 cfu/m3 in the cotton group. One hour later, the values were 10 cfu/m3 and 22 cfu/m3, respectively (p less than 0.0002). At the end of the operation, the number of particles 5 microns or larger in the air at the operative site was 278/m3 in the laminate group and 592/m3 in the cotton group. It is concluded that the use of a polypropylene coverall and laminated gowns and drapes significantly reduces the particle and bacterial contamination of the air and the bacterial sedimentation during cardiac operations. PMID- 2241339 TI - Aortic dissection with the entrance tear in transverse aorta: analysis of 12 autopsy patients. AB - Clinical and autopsy findings are described in 12 patients who had fatal aortic dissection with the entrance tear in the transverse aorta. The 12 patients represent 7% of 182 autopsies of spontaneous aortic dissection studied by us. The ages of the 12 patients at death ranged from 37 to 87 years (mean, 67 years). Eight were men; 8 had a history of systemic hypertension, and 10 had hearts of increased weight. Diagnosis of aortic dissection was made during life in only 4 of the 12 patients. All 12 patients died of rupture of the false channel within 2 weeks of onset of signs or symptoms compatible with dissection. The direction of aortic dissection from the entrance tear was entirely retrograde in 4 patients, entirely anterograde in 4 patients, and in both directions in 4 patients. Hemopericardium occurred in the first group, left hemothorax in the second group, and either in the last group. Of the 8 patients in whom the ascending aorta was involved, the retrograde dissection in each extended to the aortic root, 6 had pulmonary adventitial hemorrhage, and 4 had involvement of the arch arteries by dissection. In the 4 patients with strictly anterograde dissection, none had dissection in the arch arteries. Thus, tear in the transverse aorta causes a dissection that is usually fata, that often dissects retrogradely, and that may mimic dissection from a tear in ascending aorta. Aortic dissection from a tear in transverse aorta requires early operative intervention. PMID- 2241340 TI - Unusual opening of coronary sinus in atrioventricular septal defects. AB - The coronary sinus is an important landmark for the position of the atrial component of the atrioventricular conduction axis and, thus, assumes special relevance to the surgeon in the operating room. We describe here 2 patients with atrioventricular septal defect characterized by an unusual termination of the coronary sinus within the left atrium. We discuss the potential importance of this finding to the disposition and surgical avoidance of the conduction tissues. PMID- 2241341 TI - Myocardial preservation using lidocaine blood cardioplegia. AB - Prevention of ventricular fibrillation after aortic unclamping using lidocaine hydrochloride as an additive to cold potassium blood cardioplegia was studied prospectively in 46 patients undergoing elective myocardial revascularization. Patients were similar with respect to age, ventricular function, severity of coronary artery disease, cross-clamp time, completeness of revascularization, frequency of internal thoracic artery grafting, systemic temperature at the time of cross-clamp removal, and mean infusate volume and temperature. Patients receiving lidocaine blood cardioplegia (group 1, 23 patients) had a significant reduction in the incidence of ventricular fibrillation (22% versus 74%; p less than 0.0005) and in the mean number of cardioversion attempts required to defibrillate the heart (0.5 +/- 1.3 versus 1.9 +/- 0.97; p less than 0.0005) after cross-clamp removal compared with controls (group 2, 23 patients). There were no differences between the two groups postoperatively with regard to cardiac enzyme release, hemodynamic measurements, or clinical outcome. Patients receiving lidocaine blood cardioplegia tended to have a lower incidence of new postoperative atrial fibrillation (9% versus 26%). Ventricular function was preserved equally in both groups. We conclude that lidocaine is a safe additive to potassium blood cardioplegia and significantly reduces the incidence of ventricular fibrillation after aortic unclamping. PMID- 2241342 TI - Internal mammary artery revascularization in the patient on long-term renal dialysis. AB - Twenty-six patients on long-term renal dialysis underwent coronary artery bypass grafting. The patients were divided into two groups: group 1, (16 patients) saphenous vein bypass grafts, and group 2, (10 patients) internal mammary artery in combination with saphenous vein bypass grafts. Both groups were similar in terms of cardiac hemodynamics and previous number of myocardial infarctions, though more group 1 patients were in New York Heart Association class III or IV. Patients in group 1 received 2.9 bypass grafts per patient; patients in group 2 received 4.0 bypass grafts per patient (4 with bilateral mammary arteries). No wound healing problems occurred in either group. Blood replacement was similar for both groups (group 1, 5.5 units/patient; group 2, 5.3 units/patient). More platelets were given to group 1 patients (16.2 units/patient) than group 2 patients (3.1 units/patient). We conclude that use of the internal mammary artery in patients on long-term renal dialysis does not alter wound healing or increase blood loss in this subset of patients. PMID- 2241343 TI - Timing of operation for aortic regurgitation: relation to postoperative contractile state. AB - With angiography and pressure measurement, we determined left ventricular volume, wall stress, and systolic performance in 30 patients with aortic regurgitation before and after successful aortic valve replacement. End-systolic wall stress was greatly elevated preoperatively and decreased to normal postoperatively. Systolic pump performance assessed as ejection phase indexes was severely depressed preoperatively and improved to normal or near-normal postoperatively in most patients. The ratio of end-systolic wall stress to end-systolic volume index (ESS/ESVI), an index of myocardial contractility, was greatly decreased before operation. Postoperatively, the ratio increased in all patients, becoming normal in 12 of the 13 patients who had a preoperative ESS/ESVI of 2.9 or greater. However, 15 of 17 patients in whom the ESS/ESVI ratio was less than 2.9 still had subnormal ratios, which indicates the presence of irreversible contractile dysfunction. Stepwise multivariate analysis showed that preoperative ESS/ESVI was the only independent discriminator of postoperative normalization of the contractile function as assessed by ESS/ESVI. After aortic valve replacement, myocardial contractile state does not return to normal in a considerable number of patients. It is important to offer aortic valve replacement for aortic regurgitation before the chance for a good functional result is lost. The ESS/ESVI ratio may be a useful index in determining the timing of operation in patients with aortic regurgitation. PMID- 2241344 TI - Thoracoscopic treatment of spontaneous pneumothorax using carbon dioxide laser. AB - In an effort to improve the success rate of the previously described thoracoscopic electrocautery ablation technique of spontaneous pneumothorax, the carbon dioxide laser was evaluated in 12 patients. The recurrent (5 patients) or persistent (7 patients) spontaneous pneumothoraces were caused by rupture of (1) blebs in 6 patients, (2) intrapulmonary apical type II bullae in 3 patients, and (3) diffuse bullous emphysema, type III, in 3. The air leaks were successfully sealed in all but 1 patient with ruptured type II bulla. Surgical specimen from this single failure suggested that the entire inner lining of the bullae must be thermocoagulated. This technical modification led to successful outcome in 2 subsequent cases. With the use of carbon dioxide laser, it was possible to treat not only small blebs but all types of bullae causing spontaneous pneumothorax. Laser thoracoscopy is effective and safe in treating spontaneous pneumothorax. PMID- 2241345 TI - Prolonged extracorporeal life support of pediatric and adolescent cardiac transplant patients. AB - Options for mechanical support of pediatric patients with severe heart failure who are awaiting transplantation or have undergone transplantation are limited. This report examines 3 patients placed on extracorporeal life support (ECLS) while awaiting transplantation and 3 patients who underwent transplantation and suffered subsequent heart failure due to rejection or postoperative myocardial dysfunction. The overall survival rate was 2 of 6. The 2 surviving patients had a failing transplanted heart. There were no survivors among the patients placed on ECLS as a bridge to transplantation. In each case a contraindication to transplantation developed before a donor heart could be obtained. The mean time of ECLS support was 147.5 hours (range, 70 to 370 hours). The ECLS circuit did not affect cyclosporin levels or antirejection therapy. Extracorporeal life support can be used to support pediatric cardiac transplant patients with biventricular failure due to acute rejection or postoperative dysfunction. Although the results have been discouraging, ECLS may still have a role as a bridge to transplantation. However, complications can develop during ECLS that may preclude transplantation. PMID- 2241346 TI - Pulmonary resection combined with cardiac operations. AB - Surgical management of patients with concomitant critical cardiac disease and resectable lung lesions is controversial. During a 7-year period (1982 to 1988), 21 patients underwent combined cardiac and pulmonary operations. Patients had cardiac symptoms only; the lung lesions were found on preoperative chest roentgenograms. The pathological diagnosis was established in only 2 of the patients before operation. All underwent concurrent pulmonary resection during cardiac operations requiring extracorporeal circulation. The pulmonary operations included 17 wedge resections and four lobectomies. The final diagnoses in 8 patients with stage I non-small cell lung cancer included epidermoid carcinoma (4), adenocarcinoma (3), and bronchoalveolar carcinoma (1). Postoperatively, 1 patient required a permanent pacemaker and 1 patient died. The actuarial survival at 5 years for all patients who underwent combined procedures was 95%. The 5-year survival for the 8 patients with lung cancer was 88% compared with 100% for those with benign pulmonary pathology (p = 0.172). This experience suggests that combining pulmonary resection with cardiac operations is safe and offers a favorable prognosis to a select group of patients. PMID- 2241348 TI - Tension pneumopericardium as a complication of single-lung transplantation. AB - Tension pneumopericardium is distinctly uncommon in the adult population. We present a case of tension pneumopericardium as a complication of lung transplantation in a 54-year-old woman with thromboembolic pulmonary hypertension who underwent single-lung transplantation. PMID- 2241347 TI - Antimicrobial prophylaxis for open heart operations. AB - Between 1986 and 1988, 450 adults undergoing coronary artery bypass, cardiac valve replacement, or both were enrolled into a prospective, randomized, comparative trial of cephalothin versus cefamandole as perioperative prophylaxis. They were assessed during their hospitalization and at 6 weeks and 6 months after discharge for postoperative infectious complications. Eleven patients had major postoperative infections including 5 with sternal wound infections (three bacteremic), 6 with bacteremia, 1 with prosthetic valve endocarditis, and 3 with severe venous donor graft site infections. Eight major infections occurred in patients receiving cephalothin prophylaxis and three in patients receiving cefamandole, with all five sternal wound infections occurring in the cephalothin group. Postoperative pathogens responsible for the major infections included gram negative aerobes in 5 patients, Staphylococcus aureus in 4, and Staphylococcus epidermidis in 2. Preoperative colonizing staphylococcal isolates were not predictive of postoperative staphylococcal pathogens. Although there was no statistically significant difference in rate of major postoperative infectious complications using either cephalothin or cefamandole prophylaxis, there was a trend in favor of cefamandole. Gram-negative aerobes are becoming increasingly important pathogens in this setting. PMID- 2241349 TI - Vagal schwannoma. AB - A patient with a benign encapsulated intrathoracic vagal schwannoma is presented and the literature is reviewed. The right paratracheal tumor was identified incidentally on a chest film and excised using a right thoracotomy. Although rare, vagal schwannomas should be considered for any mediastinal mass along the vagus nerves especially when the paratracheal tumor produces minimal or no respiratory symptoms suggesting a slow-growing, encapsulated process. PMID- 2241350 TI - Catastrophic thrombosis of porcine aortic bioprostheses. AB - Hemodynamically critical thrombotic stenosis of porcine bioprosthetic valves in the aortic position without thrombotic predisposition is rare. Two patients at our institution abruptly manifested thrombotic stenosis of porcine bioprosthetic valves in the aortic position within 3 months of implantation without apparent predisposing factors. Clinicians should consider this rare but catastrophic complication in the appropriate setting. PMID- 2241351 TI - Combined repair of transposed great arteries and total anomalous pulmonary venous connection. AB - We report an unusual association of transposition of the great arteries and total anomalous pulmonary venous connection in the right atrium that was successfully repaired by a modified Mustard procedure. PMID- 2241352 TI - Circumflex artery ventricular fistula and pseudoaneurysm after mitral reoperation. AB - Prosthetic mitral valve reoperation complicated by atrioventricular groove pseudoaneurysm and circumflex ventricular fistula is presented. Ligation of the circumflex artery during mitral valve replacement is implicated after review of a previous cardiac angiogram. PMID- 2241353 TI - Mediastinal hibernoma, a rare tumor. AB - Hibernoma is an uncommon soft tissue tumor that is derived from the remnants of fetal brown fat. Review of the world medical literature revealed 90 cases, 6 of which were intrathoracic. We present the seventh case of intrathoracic hibernoma; in this case, the hibernoma was within the mediastinum without direct invasion of other structures. PMID- 2241354 TI - Acute hypercalcemic crisis after an open heart operation. AB - Acute hyperparathyroidism developed in a previously normocalcemic 64-year-old woman during the first week after a coronary operation. Prolonged QT interval in the electrocardiogram and hypercalcemia were documented on the fourth postoperative day. Neck exploration on the fifth postoperative day revealed a lower right parathyroid adenoma. Parathyroidectomy resulted in rapid and dramatic improvement of the clinical picture and normalization of laboratory values. PMID- 2241355 TI - Easy cardioplegia delivery, aortic venting, and reperfusion technique. AB - Myocardial preservation is an essential aspect of coronary revascularization as well as of other open heart procedures. As these procedures are becoming more complex, specifically myocardial revascularization, impeccable myocardial protection becomes imperative. Described is a technique that enables one to easily accomplish good myocardial preservation with minimal clutter using readily available materials. PMID- 2241356 TI - Mitral prosthetic replacement in small left atria. AB - A modified transseptal approach for exposure of the difficult mitral valve is described. This allows the surgeon to visualize the valve, especially during prosthetic replacement, in the presence of a small, friable, or noncompliant left atrium. PMID- 2241357 TI - Alternate method for revascularization of the posterior lateral coronary artery. AB - A technique is described for bypassing the posterior lateral branch of the right coronary artery by passing the vein graft beneath the inferior vena cava to avoid kinking of the graft. PMID- 2241358 TI - Collis gastroplasty: origin and evolution. AB - In 1957 J. Leigh Collis published his innovative operation for treating the difficult problem of the irreducible hiatal hernia, esophagitis, and stricture. The design of the operation was based on the relatively primitive understanding of hiatal hernia and the newly emerging concept of reflux esophagitis. A variety of antireflux operations by different surgeons emerged over the years to follow. The original Collis gastroplasty has been subsequently modified with the addition of both partial and complete fundoplication procedures. The place of the modified Collis gastroplasty-fundoplication operations in today's approach to the problems of hiatal hernia and gastroesophageal reflux disease remains unsettled. PMID- 2241359 TI - Blood conservation in cardiac surgery. AB - We reviewed current blood conservation techniques and their use in cardiac surgery. Avoidance of aspirin preoperatively is an important blood conservation measure. Patients scheduled for an elective operation should participate in autologous predonation programs. With careful monitoring, patients with major coronary artery disease can safely donate blood preoperatively. Intraoperative processing of blood withdrawn before cardiopulmonary bypass provides autologous platelet-rich plasma for infusion after reversal of heparin sodium. Blood collected from the field during operation and blood remaining in the oxygenator after bypass can also be processed to yield washed and concentrated red blood cells for reinfusion. Randomized, prospective studies document that postoperative autotransfusion is both safe and effective in reducing homologous blood use. Aprotinin reduces plasma protein activation and platelet damage during bypass. The integration of available blood conservation techniques into a comprehensive program combined with careful consideration of the indications for transfusion may allow more patients to avoid transfusion entirely. PMID- 2241360 TI - Coarctation of the aorta. PMID- 2241361 TI - Left ventricular outflow tract obstruction with aortic arch anomalies and ventricular septal defect. PMID- 2241362 TI - Diaphragmatic plication. PMID- 2241363 TI - Choice of surgical clips for mammary artery take-down. PMID- 2241364 TI - Free gastroepiploic artery graft. PMID- 2241365 TI - Oxygenator failure. PMID- 2241366 TI - Descending necrotizing mediastinitis. PMID- 2241367 TI - New technique for the arterial switch operation in difficult situations. AB - The technique described here, a modification of the Aubert operation, avoids coronary reimplantation and also eliminates the need to use artificial material to transfer coronary circulation. PMID- 2241368 TI - Transatrial approach revisited. AB - A surgical approach is described to provide excellent exposure of the interior of the left atrium and the mitral valve apparatus. PMID- 2241369 TI - Operative insertion of a transvenous left atrial pressure monitoring line. AB - We describe a technique for the insertion of a left atrial pressure monitoring line during open heart operations in infants. The procedure requires central venous cannulation with a long catheter, followed by intraoperative placement of the catheter tip through the interatrial septum into the left atrium. The technique has been used successfully in 35 infants. PMID- 2241370 TI - Postinfarction ventricular septal defect repair: retrospective thoughts and historical perspectives. AB - Evolution of surgical techniques for repair of postinfarction ventricular septal rupture initially involved differentiation of these lesions from prior experience with surgical approaches to congenital ventricular septal defects, which were in the main not applicable. Second, understanding of the differing anatomical locations of postinfarction ventricular septal defects required innovation in terms of the location of the cardiotomy and type of repair necessary to achieve a successful result in any given patient. The gradual appreciation of different clinical courses pursued by patients after postinfarction ventricular septal rupture both in terms of location of the defect and the degree of right ventricular functional impairment has led to increased urgency relative to the timing of surgical repair. The incorporation of specific anatomical concepts of surgical repair and better understanding of the time course of physiological deterioration of patients can ultimately lead to an integrated approach aimed toward improved salvage of patients suffering this catastrophic complication of acute myocardial infarction. PMID- 2241371 TI - Intraoperative echocardiography. AB - Intraoperative echocardiography has emerged as a new technique by which the cardiac surgeon can more precisely define the operative anatomy and physiology, immediately evaluate the results, and more accurately monitor left ventricular function in the operating room. This review summarizes the current applications of intraoperative two-dimensional and Doppler echocardiography in both the epicardial and transesophageal forms, and discusses the advantages and possible limitations of these methods in the practice of clinical cardiac surgery. PMID- 2241372 TI - Spasm of arterial conduits in aorta-coronary bypass grafting. PMID- 2241373 TI - Chest wall recurrence of lung cancer after transthoracic fine needle aspiration biopsy. PMID- 2241374 TI - Plastic struts for delayed sternal closure. PMID- 2241375 TI - Individual ligation technique. PMID- 2241376 TI - Cardiac transplantation for neonates with hypoplastic left heart syndrome. PMID- 2241377 TI - Surgical treatment of Wolff-Parkinson-White syndrome. PMID- 2241379 TI - Facile retrograde cardioplegia: transatrial cannulation of the coronary sinus. AB - The benefits of coronary sinus (CS) cardioplegia are well known, yet CS cardioplegia is not used widely owing to the need for bicaval cannulation, snares, and an atriotomy. We designed and used in 225 consecutive patients a catheter containing a flexible removable stylet that, when shaped into a hockey stick configuration, enabled blind intubation of the CS through a small pursestring in the right atrium, guided easily into the CS using a finger on the atrioventricular groove at the inferior vena cava. The CS was intubated in all patients; a pressure-limited balloon at the catheter tip was inflated after cross clamping. An integral distal pressure line measured CS pressure. Catheters were placed distally within the great cardiac vein beyond the posterior interventricular vein; the position did not alter cooling: right ventricular free wall, septum, and left ventricular free wall temperatures were 7 degrees +/- 2 degrees, 8 degrees +/- 2 degrees, and 7 degrees +/- 2 degrees C, respectively, after an initial 10 mL/kg of blood cardioplegia. Transatrial CS cardioplegia was used in 45 aortic valve replacements, 22 mitral valve replacements, 4 triple valve replacements, 6 congenital lesions, and 148 coronary revascularizations, including 40 redo operations. Atheromatous material was routinely flushed retrogradely from cut old vein grafts during revascularization; 70 revascularizations (47%) were performed urgently for acute infarction or jeopardized myocardium. No heart block or CS injury occurred, and inotrope use dropped to 10% of patients (from 38% in the previous 256 patients with antegrade blood cardioplegia). We conclude that the CS can be cannulated transatrially and that CS cardioplegia is more facile than antegrade cardioplegia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241380 TI - Cardiac transplantation for hypoplastic left heart syndrome: a modified technique [see comment]. AB - A modified technique of infant orthotopic cardiac transplantation with arch reconstruction using bicaval cannulation is described, and the results in 4 infants with hypoplastic left heart syndrome are presented. This technique minimizes donor myocardial ischemic time and recipient circulatory arrest time. PMID- 2241378 TI - Treatment of postoperative infection of ascending aorta and transverse aortic arch, including use of viable omentum and muscle flaps. AB - Postoperative infection of the ascending aorta and aortic arch in 40 patients was treated by antibiotic therapy alone (4 patients) or by operation and lifelong suppressive antibiotic therapy (36 patients). Complications of infection included antibiotic-resistant infection, infected false aneurysm, rupture of suture line, aortocutaneous fistulas, aortic-right ventricular fistulas, arterial embolus, aortic valve insufficiency, aortobronchial fistula, mediastinal abscess, and chest wall problems. These were treated by a variety of operations including composite valve-graft replacement, graft replacement, patch-graft closure of false aneurysm, simple suture of disrupted suture lines and false aneurysm, and debridement of mediastinum and chest wall. The area of reconstruction was covered, and mediastinal dead space was reduced by mobilization of viable tissue, including local tissue and distant structures such as flaps of muscle and omentum. Thirty-three patients (83%) were early survivors, and 28 patients (70%) were alive and well at last follow-up 4 months to 6.5 years after operation. PMID- 2241381 TI - Tracheal reconstruction with polytetrafluoroethylene graft in dogs. AB - Use of prosthetic materials for long-segment tracheal reconstruction has been limited owing to infection, graft migration, ingrowth of fibrous tissue, and stenosis. Polytetrafluoroethylene (PTFE) is flexible and porous, and it may resist infection more than previously used materials. We evaluated PTFE for use in long-segment tracheal reconstruction. A 5-cm segment of trachea was resected in 9 dogs and replaced with a 20-mm reinforced PTFE graft using 4-0 Vicryl sutures. In 2 control dogs, one tracheal arch was resected and a primary anastomosis was performed. The animals were followed up with weekly bronchoscopy and endoscopic photography. Euthanasia was performed at 16 weeks or when signs of respiratory distress developed. At postmorten examination, the anastomoses were examined grossly and with light and scanning electron microscopy. In all 9 dogs that underwent tracheal replacement with PTFE, granulation tissue developed at the anastomoses resulting in airway obstruction after 3 to 8 weeks. No epithelial growth occurred over the graft between the anastomoses. The control animals did well. We conclude that granulation tissue formation at the anastomosis and the lack of respiratory epithelial ingrowth across the graft makes PTFE unsuitable for long-segment tracheal reconstruction. PMID- 2241382 TI - Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass. AB - The role of perfusion pressure and flow during cardiopulmonary bypass with moderate hypothermia and hemodilution in the development of new postoperative renal or clinically apparent cerebral dysfunction was examined in 504 adults. Cardiopulmonary bypass flow was targeted at greater than 40 mL.kg-1.min-1 and pressure at greater than 50 mm Hg. Flows and pressures less than target occurred in 21.6% and 97.1% of patients, respectively. Fifteen patients (3.0%) suffered new renal and 13 (2.6%) new central nervous system dysfunction. Low pressure or flow during cardiopulmonary bypass, expressed in absolute values or in intensity duration units, were not predictors of either adverse outcome. Multivariate analysis identified use of postoperative intraaortic balloon counterpulsation (p less than 10(-6], excessive blood loss in the ICU (p less than 10(-4], need for vasopressors before cardiopulmonary bypass (p less than 10(-4], postoperative myocardial infarction (p less than 10(-3], emergency reoperation (p less than 0.002), excessive postoperative transfusion (p less than 0.02), and chronic renal disease (p less than 0.03) as independent predictors of postoperative renal dysfunction. Independent predictors of postoperative central nervous system dysfunction were cardiopulmonary resuscitation in the intensive care unit (p less than 10(-6], intracardiac thrombus or valve calcification (p less than 0.02), and chronic renal disease (p less than 0.03). Age greater than 65 years (40.7% of patients) did not predict either outcome. We conclude that failure of the native circulation during periods other than cardiopulmonary bypass rather than the flows and pressures considered here is the major cause of renal and clinically apparent central nervous system dysfunction after cardiac operations. PMID- 2241383 TI - Ultrasonic debridement during mitral valve reconstruction for calcified mitral stenosis. AB - An ultrasonic device in conjunction with open mitral commissurotomy was applied in 8 patients with heavily calcified, stenosed mitral valves. In 6 patients, reconstruction of the mitral valve by debridement of the leaflet calcification with the device was successful. Two patients required valve replacement because of an increase in preexistent mitral regurgitation caused by excessive decalcification. The ultrasonic device proved to be a useful and effective adjunct for salvaging the heavily calcified mitral valve, which would otherwise have to be replaced. PMID- 2241384 TI - Repair of flail anterior leaflets of tricuspid and mitral valves by cusp remodeling. AB - We present an alternative approach to extensive rupture of the chordae tendineae leading to flail anterior leaflets. Resection of the affected cusp segment, suture of the cut edges, and extensive plication of the segment of annulus devoid of leaflets abolished massive regurgitation while maintaining an adequate valve orifice. PMID- 2241385 TI - Thoracic spinal fractures and aortic rupture: a significant and fatal association. AB - We analyzed the frequency of occurrence of traumatic aortic rupture (TAR) in patients with and without thoracic spinal fractures. Among 4,676 blunt chest trauma victims admitted to the hospital between 1972 and 1988, 148 (3.2%) suffered one or more thoracic vertebral fractures. There were 73 patients with one or more fractures of the first eight thoracic vertebrae (T1 to T8); of these 73, 4 also suffered TAR (5.5%). There were 4,603 patients without fractures of T1 to T8, and 64 of these patients also suffered TAR (1.4%). This difference was significant by the chi2 and Fisher exact tests, p = 0.00378 and p = 0.021003, respectively. Additionally, all 5 patients with TAR and thoracic vertebral fractures died. We conclude that patients with one or more fractures of T1 to T8 have a statistically significant increase in the incidence of TAR. PMID- 2241387 TI - Pleuropulmonary morbidity: internal thoracic artery versus saphenous vein graft. AB - Although use of the internal thoracic artery (ITA) for coronary artery bypass grafting results in superior graft patency and improved patient survival, our initial clinical observations suggested an increased incidence of pleuropulmonary morbidity with its use. One hundred consecutive patients with left ITA grafts were studied prospectively and compared with a consecutive retrospective group of 100 patients undergoing coronary artery bypass grafting with saphenous vein grafts only. Preoperative, postoperative day (POD) 2, POD 6, and postoperative week 8 chest roentgenograms were analyzed for atelectasis and effusion. Postoperative left lower lobe atelectasis was common in both groups on both POD 2 (saphenous vein, 43%, versus ITA, 53%; not significant) and POD 6 (saphenous vein, 40%, versus ITA, 41%; not significant). There was a significantly higher incidence of pleural effusion on POD 6 in the ITA group (84% versus 47%; p less than 0.05) but most of these were small. There was more chest tube drainage (1,413 versus 1,028 mL; p less than 0.01) and a greater need for secondary thoracostomy or thoracentesis (4% versus 0%) in the ITA group. The left pleural space was opened in 67 of the 100 ITA patients but pleurotomy did not appear to influence postoperative morbidity. We conclude that use of the internal thoracic artery for coronary artery bypass grafting results in a small but significant increase in pleuropulmonary morbidity. PMID- 2241386 TI - Cardioplegia-induced damage to ischemic immature myocardium is independent of oxygen availability. AB - The known benefits of hypothermic pharmacological cardioplegia in protecting the ischemic adult heart may not extend to children. Protection of the ischemic immature rabbit heart with hypothermic Krebs-Henseleit bicarbonate buffer is better than with hypothermic St. Thomas' II cardioplegic solution. We investigated whether the availability of oxygen in the preischemic perfusate is responsible for the increased tolerance to ischemia of immature (7- to 10-day old) hearts perfused with Krebs buffer in comparison with St. Thomas' II solution immediately before ischemia. After obtaining preischemic control data in the "working" mode, we perfused hearts (n = 8 per group) for 3 minutes with hypothermic (14 degrees C) Krebs buffer or hypothermic St. Thomas' II solution saturated with 0%, 25%, or 95% oxygen. This was followed by 2 hours of global ischemia at 14 degrees C. Hearts were reperfused for 15 minutes in the Langendorff mode and 35 minutes in the working mode, and recovery of function was measured. For preischemic oxygen concentrations of 0%, 25%, and 95%, recovery of aortic flow in hearts protected by hypothermia alone during ischemia was 74% +/- 9%, 82% +/- 4%, and 99% +/- 2% of preischemic values, respectively. In hearts protected by hypothermia plus cardioplegia, the values were 69% +/- 6%, 72% +/- 3%, and 86% +/- 5%, respectively. Thus, at equal oxygen concentrations, recovery of postischemic function was better in hearts protected by hypothermia alone compared with hypothermia plus cardioplegia. We conclude that factors other than oxygen availability are responsible for the damaging effect of St. Thomas' II solution on the ischemic immature rabbit heart. PMID- 2241388 TI - Medical management of acute traumatic rupture of the aorta. AB - Surgical reconstruction is the treatment for acute traumatic aortic rupture and should be accomplished immediately in most patients. In patients in whom concomitant injuries or the development of life-threatening complications preclude safe and successful aortic reconstruction, pharmacological intervention to reduce the risk of free aortic rupture may be considered. Surgical reconstruction can then be more safely performed under controlled elective circumstances. PMID- 2241389 TI - Surgical epicardial ablation of left ventricular pathway using sling exposure. AB - We report our experience with 43 consecutive patients with left free wall pathways operated on since December 1988 using a modified direct epicardial approach through a medial sternotomy, without the adjunct of normothermic cardiopulmonary bypass. The left atrioventricular sulcus is exposed by dislocating the heart cephalad and to the right using a sling made of a large sponge passed around the ventricle through the transverse sinus. While the arterial pressure is monitored, the heart is positioned to obtain adequate exposure without compromising the ventricular function. The left atrioventricular junction is exposed using a direct approach. The epicardium is incised along the ventricular edge and a plane of dissection is identified and opened using blunt dissection over the ventricular wall. The entire left atrioventricular junction can be exposed. After dissection, electrophysiological testing is repeated to assess accessory pathway conduction. Epicardial cryoablation was used when accessory pathway conduction was not present (42 patients). Transmural cryoablation was used under normothermic cardiopulmonary bypass when accessory pathway conduction persisted after dissection (subendocardial pathway). In all, cardiopulmonary bypass was not used in 41 patients. There was one early relapse that required transmural cryoablation. There were no complications. PMID- 2241390 TI - Bronchial anomaly of the right upper lobe. AB - This case report presents a rare anomaly of right upper lobe bronchial anatomy. During routine right upper lobe resection for carcinoma, a common right upper and middle lobe bronchus was found. The resection was completed as a right upper and middle bilobectomy. Knowledge of this uncommon variant was beneficial in performing the pulmonary resection. A review of the literature is presented. PMID- 2241392 TI - Left recurrent laryngeal nerve paralysis: an unusual presentation of histoplasmosis. AB - A case of histoplasmosis seen as left recurrent laryngeal nerve paralysis in a 49 year-old man is described. The patient had roentgenographic findings of a solitary, noncalcified left upper lobe mass and mediastinal adenopathy. Tissue diagnosis of histoplasmosis was obtained using a thoracotomy, allowing institution of appropriate treatment. PMID- 2241391 TI - Squamous carcinoma metastatic to the sternum. AB - A 63-year-old man had a 10 x 16-cm sternal mass 18 months after a second aortocoronary bypass operation. The resected lesion was a metastatic tumor of squamous histology. No primary tumor was found. The diagnostic work-up and treatment options are presented. PMID- 2241393 TI - Malignant thymoma presenting as intracardiac tumor and superior vena caval obstruction. AB - A case of malignant thymoma with intracardiac infiltration and intrinsic superior vena caval obstruction due to the tumor is reported. Intracardiac invasion by a thymoma is rare and for this reason is believed worthy of a report. PMID- 2241394 TI - Job's syndrome: a rare cause of recurrent lung abscess in childhood. AB - A clinical syndrome characterized by recurrent staphylococcal infection of the skin and respiratory tract from birth was described in 1966 and referred to as Job's syndrome. Marked hyperimmunoglobulinemia E was later found to be associated with this syndrome. This article describes a case of Job's syndrome as a cause of recurrent lung abscess during childhood necessitating lung resection. PMID- 2241395 TI - Easy dissection of hard and thickened pericardium on constrictive pericarditis. AB - The keys to successful pericardiectomy for constrictive pericarditis are early operation and as complete a pericardiectomy as possible. With the high-speed burr it is easy and safe to dissect the calcified pericardium and define the epicardium even in a small operative field such as the inferior or posterior portion of the heart. This method has the important ability to perform very complete pericardiectomy. PMID- 2241396 TI - [Follow-up studies on systemic arterial hypertension in Mexico]. PMID- 2241397 TI - [The effect of gelfoam embolism in vascular conduction and critical pressure in the isolated canine lobe]. AB - Pulmonary pressure-flow curves, hemodynamic and blood gas parameters in West's zone II condition were obtained in nine isolated in situ left lower lobes (LLL) before (condition A), and after 15, 30 and 60 minutes of lobar gelfoam embolization (GE) (condition B) in order to know the natural history of this model. After GE a decrease in PaO2 and lobar O2 were noticed (p less than 0.05). Vascular conductance (p less than 0.001) and lobar blood flow decreased (p less than 0.05), accompanied by a significant increase in the inflow (p less than 0.01) and in the mean closing pressures (p less than 0.01). These parameters did not change during the time of observation at condition B. Nor the cardiac output or the minimal closing pressure changed in relation to condition A. LLL angiographic findings showed evidence of arterial occlusion and the pattern of obstruction was not homogeneous. Lobes histology showed occluded arteries of more than 300 micrometers of diameter. We concluded that in this canine model of increased pulmonary vascular resistance, pulmonary vascular conductance and mean closing pressure change, remain stable during 60 minutes after GE allowing us to know the natural history of the preparation. Condition than allow to perform and evaluate other interventions on lung vascular mechanics in the experimental setting of pulmonary embolization. PMID- 2241398 TI - [Transesophageal atrial stimulation]. AB - Considering that catheterization of the esophagus is a relatively easy procedure, we studied the electrical transesophageal atrial stimulation in ninety patients (age range 15 to 75 years (mean 42 +/- 9 years). A multipolar electrode catheter was introduced through the nose into the esophagus of each patient and fixed in position at a site where the simultaneous recording of intraesophageal unipolar electrocardiographic derivations showed the greatest P wave potentials. Electrical atrial capture through the esophagus was obtained at frequency values higher than that of the heart, with lower voltages needed for atrial stimulation at the site in which the unipolar recording of the intraesophageal P wave was of highest amplitude. The difference of potential used was between 6 and 30 volts, with the highest values corresponding to patients with megaesophagus, whereas values below 15 volts were tolerated without major discomfort. Electric pulses of more than 10 ms duration did not significantly reduce the intensity of electric current needed to produce the atrial command. The stimulation bipole (area to be stimulated per pole, 0.72 cm2) had an interpolar distance of 22 or 30 mm, our overall experience showing that distances up to 44 mm did not require higher voltages. No cases of esophageal damage or severe arrhythmia were reported due to stimulation. In the present study, programmed transesophageal stimulation proved to be a good option for the evaluation of sinus node function and for the study and reversal of paroxysmal supraventricular tachycardia attacks by a reentry mechanism, representing in some cases an alternative approach for the study of atrioventricular conduction. PMID- 2241399 TI - [American trypanosomiasis and chronic Chagas cardiopathy at the "Ignacio Chaves" National Institute of Cardiology]. AB - The cumulated experience at the Instituto Nacional de Cardiolog ia Ignacio Chavez during the period from 1977 to 1988 in regard of American Trypanosomiasis (AT) and its sequelae, chronic Chagasic Cardiopathy (CHC) was reviewed. There are 39 cases. One was an acute myocarditis in a child 16 months old. Three, subacute diseases among young patients and 35 cases of chronic disease with severe heart compromise. Heart failure was the most important manifestation in 19 patients. Arrhythmia was the dominant one in 8 cases. Both conditions did occur in 8, 2 had Stokes Adams syndrome as presenting complaint and one had pulmonary embolism. The surface EKG was always abnormal and heart enlargement was noted in 36 cases on chest X rays. All patients had serologic evidence of antitrypanosoma antibodies, 28 had heart reactive antibodies in their serum, 24 had polyclonal hypergammaglobulinemia and the same proportion had rheumatoid factor. Only the acute case showed another non-organ specific autoantibody. Echocardiography was useful to show dilatation of all cavities, left ones were more severely affected, abnormal movement was also detected with lower frequency, apical aneurysm and left ventricular hypertrophy were rarely detected. Fifteen out of 16 cases studied by angiogram did show normal coronary arteries, abnormal movement was demonstrated in 62% and apical aneurysm was present in 4 cases. Studies with EKG monitoring (Holter) and electrophysiology confirmed electrical abnormalities. Although once considered an exotic disease, CHC is probably underdiagnosed because the lack of methodic studies looking for epidemiologic, clinical and seroimmunologic features in patients with dilated myocardiopathy. Cardiologist practicing in south and southeast states in Mexico should be aware of this heart ailment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241400 TI - [The diagnosis of perioperative myocardial infarction in heart surgery]. AB - Fifty three consecutive patients undergoing open heart surgery were prospectively studied to assess current techniques for diagnosing perioperative myocardial infarction (PMI). All patients had preoperative and postoperative electrocardiograms, serial determinations of serum creatine phosphokinase (CK), myocardial fraction of CK (CK-MB) and scintigraphy with technetium-99m labeled pyrophosphate. Seven patients (13.2%) sustained perioperative myocardial infarction. Four of these patients exhibited abnormal Q waves, and one poor R wave progression. Three of them had a positive scintigram. Two patients with a non-Q-wave infarction had a abnormal radioisotopic imaging. The CK and CK-MB were higher in patients with infarction (818.1 U) than in those without this complication (349 U) p less than 0.05. The relative sensitivity and relative specificity of given variables in the diagnosis of PMI were as follows: electrocardiogram 71.4% and 97.5% respectively; scintigraphy 71.4% and 94.1%; and serum enzymes 100% and 71.8%. Age, incidence of prior myocardial infarction, unstable angina, elevated left ventricular filling pressure, number of diseased coronary arteries, and number of grafts per patient did not correlate with PMI. Duration of extracorporeal circulation and number of electric shocks during surgery were slightly higher in the infarction group, but the difference was not significant. These results indicate that the combination of these three diagnostic procedures is the best way to evaluate myocardial damage after open heart surgery. PMID- 2241401 TI - [Unstable angina: clinical and angiographic characteristics of 140 cases]. AB - We conducted a study on the clinical and angiographic characteristics of 140 patients with unstable angina. Average age of 57, male/female ratio 4 to 1. The most frequent risk factors: tobacco smoking (73%) and arterial hypertension (42%). They had old infarct (57%), and unstable angina at rest (37%). We did early submaximal stress test to 31% of them; in 38.6% test was stopped due to angina, 25% for fatigue. 91% had ischemic changes, there weren't any severe complications. Regarding significant coronary obstruction: 20% had one vessel, 26% two, 50% three and left trunk 4%. Normal ventriculogram 43%. Eight patients died; the causes were: disease of the trunk (37.5%) and "active" angina (87.5%), 25% during catheterization . All survivors responded to medical treatment. 54 patients were not candidates for surgical treatment, among them 70.3% were released in class I (NYHA). At follow up 90% were in class I-II, 12% had unstable angina recurrence, 3% had acute infarct. In the pathogenesis of unstable angina intervene fixed atherosclerosis, obstructive lesions, repetitive spasms and non occlusive thrombosis, this physiopathologic behavior is responsible for the stages of ischemic activity. Treatment should be directed to maintain the balance between the distribution and the demand of O2, and also treating spasm and thrombosis. PMID- 2241402 TI - [Life style, family history and personal pathology in relation to arterial hypertension in students of the Medical Faculty of UNAM]. AB - Arterial hypertension (HA) is a public health problem, 15 to 30% of adults in our country suffer it. There are different facts that influence its outcome. Among young people the main factors are: alcoholism, smoking tobacco, overweight, diabetes, family history, sedentarism and psychological aspects. The main object of this study, was to detect the risk factor for the development of HA in the students of the University. For this search 489 sophomore students class at the Medical School of the University of Mexico (UNAM), between 17 and 24 years old, were studied. Our results showed that positive family history was more prevalent among females. Among males life-style factors were more significant, the main factor was sedentarism, whereas lesser factor was overweight. The prevalence of HA was higher for diastolic hypertension than for systolic. We concluded there are many risk factors that influence the development of HA, which are distributed in a different way according to gender preventive measures are recommended. PMID- 2241403 TI - [Clinical development of the in-hospital phase of acute myocardial infarction in patients treated with intravenous streptokinase]. AB - In order to determine the clinical in-hospital course of patients with acute myocardial infarction treated with intravenous Streptokinase (SK), 132 patients were studied divided as follows: Group I: 44 patients who arrived to the hospital within 6 hours from the onset of symptoms and received fibrinolytic therapy. Group II: 44 patients who arrived more than 6 hours delay and did not receive SK. Group III: 44 patients who arrived less than 6 hours delay but they did not receive SK. The overall hospital mortality was 2.2% in the SK recipients versus 4.4% in the group II (Odd ratio 0.95, p = NS) and 13.6% in group III (Odd ratio 0.79, p greater than 0.05). The incidence of hemorrhagic episodes was not increased in SK recipients. In-hospital period differences between groups were explained by protocol studies and postoperative complications in patients that needed further revascularization procedures. PMID- 2241404 TI - [Ventricular activation time of the fetal heart]. AB - The prenatal risk determined by smoking pregnant woman was studied by a fetal electrocardiogram at different gestational ages. There were 28 low risk pregnancy women selected and qualified by means of an 80% completion of the Perechtl optimal criterion, 13 which smoked more than 5 cigarettes daily and 15 (53%) non smokers. A new computerized technique was defined and applied for recording a continuous fetal electrocardiogram for long periods of time. Measurements of the QRS complex, inscription time of the intrinsecoid deflection (TIDI) and intrinsecoid deflection (DI) lengths were taken and compared with the gestational age. It was observed that there is a relationship of statistical significance (p less than 0.005) between the gestational age and the QRS length in the nonsmoking women. This relationship was smaller in the smoking group and furthermore it was negative when comparing the gestational age with the TIDI. There was no statistical difference in the weight of the child at birth in both groups, nevertheless the fetal electrocardiogram is useful in determining the development of the ventricular mass. In the smoking group the lack of relationship between the QRS length and the gestational age is probably owing to the retarded cardiac development and expressed ahead of all other features in fetal growth including low weight at birth. PMID- 2241405 TI - [Tetralogy of Fallot with abnormal coronary arteries]. AB - Between 1980 and 1989 nine patients with Tetralogy of Fallot with abnormal coronary artery underwent surgical treatment. In all but one, the abnormal coronary artery was identified at surgery. Seven (group I) had the anterior descending coronary artery arising from the right coronary artery; one (group II) with had the right coronary artery arising from the left coronary artery and finally, the only case of the group III had left coronary artery arising from the main pulmonary artery. Systemic-pulmonary anastomosis was done in two cases of the Group I, in one due to severe hypoplasia of the pulmonary ring and main pulmonary artery and in the other due to the anomaly of the coronary artery. In the case of the Group II the right coronary artery was accidentally cut and the patient developed right ventricular infarction and died. All surviving are in NYHA functional class I. Nowadays, the preoperative evaluation of Tetralogy of Fallot, can be done by echocardiography despite the possibility of its association with abnormal coronary artery. In special cases aortography or arterial coronarography should be considered. PMID- 2241406 TI - Effects of clonidine, yohimbine and eserine on the quantified EEG of rats. AB - The effects of three different classes of drugs were analyzed on the EEG of rats on two cortical derivations (parieto-occipital and fronto-occipital) and one deep structure, the locus coeruleus. Clonidine, an alpha 2-agonist (0, 0.10, 0.30 and 0.50 mg/kg, i.p.), yohimbine, an alpha 2-antagonist (0, 2, 4 and 8 mg/kg, i.p.) and eserine, an anticholinesterase (0, 0.10, 0.30 and 0.50 mg/kg, i.p.), affected the EEG in different significant ways. Clonidine significantly decreased frequency in the theta-band (3.7-7.5 Hz) and increased it in the alpha-band (7.6 13.5 Hz). A general significant increase in power was also observed. For yohimbine, there was a significant dose-dependent increase of power, particularly in the theta-, alpha- and beta-bandwidth. Moreover, its effects on EEG varied in accordance to the derivations analyzed. Finally, eserine significantly decreased power in the high frequency bandwidths. A synchronization, as a function of dose, with a peak at 5-6 Hz was observed shortly after its administration. The results are discussed in terms of the potentiality of the technique of quantitative pharmaco-electro-encephalography and drug interaction studies in the analysis of psychoactive substances. PMID- 2241407 TI - Ribavirin-induced behavioral, body temperature and electrocortical spectra effects in the rat. AB - Behavioral, electrocortical spectra and body temperature effects, following a single intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of ribavirin, were studied in male adult rats. Ribavirin, when administered i.p., induced squatting posture, sedation, electrocortical synchronization, piloerection and a slight decrease of tactile and/or auditory stimuli/responses lasting from 45 min to 16 hr, as well as a longer lasting hypothermic effect. Following i.c.v. administration, ribavirin (50, 100 and 200 micrograms) elicited a soporific effect and produced changes in the electrocortical spectra. Pretreatment, 15 min before, with either prazosin (10 mg/kg, i.p.), an alpha 1 adrenoceptor blocker, or piperoxan (20 mg/kg, i.p.) and yohimbine (1 mg/kg, i.p.), two alpha 2-adrenoceptor blockers, or naloxone (1 mg/kg, i.p.), an opioid antagonist, did not prevent the hypothermic and behavioral effects induced by i.p. or i.c.v. administration of ribavirin. The present findings exclude an involvement of alpha-adrenergic and opioid neurotransmission in mediating the hypothermic, electrocortical and behavioral effects induced by ribavirin. PMID- 2241409 TI - In vitro cardiac electrophysiological effects of prenylamine. AB - In order to get information on some of the effects of prenylamine (bradycardic effect, negative inotropic effect, triggering of "torsade de pointes"), we studied with intracellular microelectrodes its electrophysiological actions on guinea-pig sinus node and papillary muscle, on sheep Purkinje fibers and rabbit sino-atrial node isolated myocytes. Prenylamine (10(-6)-10(-5) M) reduced the firing rate of sinus node preparations. This effect was associated with a slowing of the rates of diastolic depolarization, of depolarization and of repolarization, and with a slight depolarization of the maximum diastolic potential. A dose-dependent decrease of the slope of the first 100 msec of the diastolic depolarization was observed. Prenylamine (10(-6) M) also reduced the amplitude of the pacemaker current (If) recorded using the patch-clamp technique from rabbit sino-atrial node cells. Prenylamine (3 x 10(-7)-3 x 10(-6) M) dose dependently reduced contractility of Purkinje fibers; the effect was associated with a lowering of the plateau, a decrease of the maximum rate of depolarization and a shortening of the action potential duration. Prenylamine was also able to abolish early and delayed after-depolarizations which are two kinds of calcium dependent electrical activities relevant for the genesis of triggered arrhythmias, such as "torsade de pointes". It is concluded that prenylamine, a nonselective calcium antagonist, presents an intriguing in vitro electrophysiological profile which makes any extrapolation to its in vivo pharmacology extremely complex. PMID- 2241408 TI - Cross-dependence on ethanol and pentobarbital in rats reinforced on diazepam. AB - Cross-dependence on ethanol and pentobarbital was studied in rats reinforced on diazepam, using an intravenous self-administration method. Five rats were allowed to self-administer diazepam 2.0 mg/kg per injection intravenously by pressing a lever on a continuous reinforcement schedule over a 20 day period. The total daily dose of diazepam delivered reached 50 mg/kg/day. Thereafter, ethanol (50 or 100 mg/kg per injection) and then pentobarbital (6 mg/kg per injection) were substituted for diazepam for 3 and 2 days, respectively. During these substitution periods, responding for self-administration, food intake and body weight were recorded. When ethanol was substituted, self-administration responding increased and then decreased. Food intake and body weight also decreased during this period. These changes during the ethanol substitution session resembled those observed during withdrawal sessions. In contrast, when pentobarbital was substituted, no significant changes in self-administration responses, food intake or body weight were seen. These findings suggest that diazepam produces cross-dependence on pentobarbital, but not on ethanol at the doses used in this experiment. PMID- 2241411 TI - Effects of magnesium sulfate and nifedipine on regional cerebral blood flow during middle cerebral artery ligation in the rat. AB - The effects of magnesium sulfate and nifedipine on regional cerebral blood flow were compared after ligation of the middle cerebral artery in rats. Twenty-one rats were divided into 3 groups of 7 each. The groups were the magnesium group, the nifedipine group, and the control group. Animals were anesthetized with pentobarbital. The middle cerebral artery was ligated, and magnesium sulfate was infused at a rate of 16 mg/kg/min for 30 min in the magnesium group, and nifedipine was infused at a rate of 10 micrograms/kg/min for 45 min in the nifedipine group. Using [14C]-iodoantipyrine, regional cerebral blood flow was measured 1 hr after middle cerebral artery ligation in the ischemic cortex, contralateral cortex, thalamus, hypothalamus, pons, medulla and cerebellum. In the control group, the mean cerebral blood flow was 30.7 +/- 12.2 ml/min/100 g in the middle cerebral artery-ligated cortex, and 75.9 +/- 10.5 ml/min/100 g in the contralateral cortex. Nifedipine did not significantly alter the cerebral blood flow in any of the brain regions studied. However, in the magnesium group, the regional cerebral blood flow in the middle cerebral artery-ligated cortex was significantly higher (64.2 +/- 8.8 ml/min/100 g) than that recorded in the control and nifedipine groups, whereas the regional cerebral blood flow in the contralateral cortex was not significantly different from other groups. Our data showed that magnesium was effective and superior to nifedipine in improving blood flow in the ischemic area of the brain. PMID- 2241410 TI - Comparison of the cardiac electrophysiologic effects of amitriptyline and clomipramine in the dog after myocardial infarction. AB - The effects of the tricyclic antidepressants amitriptyline and clomipramine on intraventricular conduction, effective refractory period and incidence of ventricular arrhythmias induced by programmed stimulation, were studied in the dog heart after myocardial infarction. Amitriptyline, at doses of 1 to 3 mg/kg, significantly slowed ventricular conduction of the infarcted zones in a frequency dependent and a dose-dependent manner. Amitriptyline, at doses of 2 and 3 mg/kg, slightly slowed conduction in normal zones. The effective refractory period was prolonged by amitriptyline at a dose of 2 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. On the other hand, the depressant effect of clomipramine, at doses of 1 to 3 mg/kg, on the conduction of infarcted zones was lower than that of amitriptyline, whereas the severely depressed conduction in the infarcted zone was obviously slowed by clomipramine. The incidence of ventricular arrhythmias did not significantly increase with clomipramine. From the present results, clomipramine seems to have a lower cardiac toxicity than amitriptyline, although clomipramine produces a slight depression of conduction in infarcted zones. PMID- 2241412 TI - Protective effect of KB-2796, a new calcium antagonist, in cerebral hypoxia and ischemia. AB - The protective effect of KB-2796, a new calcium antagonist possessing a selective vasodilator activity on cerebral vessels in cerebral hypoxia and ischemia, was investigated in both in vivo and in vitro. KB-2796 showed an apparent protective potency against complete ischemia induced by decapitation, normobaric hypoxia and KCN-induced death in mice. KB-2796 (50 mg/kg, p.o.) significantly prolonged survival time in gerbils with bilateral carotid ligation. In guinea-pig hippocampal slices, the amplitude of the population spike recorded from the dentate granule cell layers, in response to electrical stimulation of the perforant path, gradually decreased during mild hypoxia (20% O2 + 75% N2 + 5% CO2), with a tendency to recover to pre-hypoxic levels during reoxygenation (95% O2 + 5% CO2). Pretreatment with KB-2796, at a concentration of 1 microM, significantly accelerated the recovery of the population spike during the reoxygenation period. These results suggest that the protective effect of KB-2796 in cerebral hypoxia and ischemia is due in part to a mechanism independent of its effects as a cerebral vasodilator. PMID- 2241413 TI - Effects of calcium entry blockers on KCl- and 5-hydroxytryptamine-induced contractions of human umbilical arteries. AB - The effects of Ca2+ removal and of the calcium entry blockers, nicardipine and nifedipine, on contractions of isolated human umbilical arteries, elicited with KCl and 5-hydroxytryptamine, were investigated. Withdrawal of Ca2+ caused inhibition of both KCl and 5-hydroxytryptamine responses, but the maximum effect of KCl in Ca2(+)-free medium was recuperated by increasing the KCl concentration. The maximum effect of 5-hydroxytryptamine, however, was recuperated only when Ca2+ was restored to the medium. Consistently with an inhibition in Ca2(+)-free medium, calcium entry blockers produced a concentration-dependent relaxation of human umbilical artery strips precontracted with KCl and 5-hydroxytryptamine, and inhibited the concentration-dependent contraction elicited by these stimuli. Our results indicate that contractile responses of the human umbilical arteries are dependent on extracellular Ca2+ for both KCl and 5-hydroxytryptamine. Although Ca2+ entry was sensitive to both nicardipine and nifedipine, the differences between the effects of these dihydropyridines with the two experimental approaches we used were not always conclusive. PMID- 2241414 TI - Antihypertensive and diuretic effects of NZ-105, a novel dihydropyridine derivative. AB - Studies on the antihypertensive and diuretic actions of NZ-105, a new dihydropyridine derivative, were performed in comparison with nicardipine. NZ-105 and nicardipine (5, 10 and 20 mg/kg, p.o.) dose-dependently decreased systolic blood pressure in three types of experimentally hypertensive rats, including spontaneously hypertensive rats, renal hypertensive rats and deoxycorticosterone acetate-salt hypertensive rats and normotensive Wistar-strain rats. The hypotensive effects were larger in hypertensive rats than in normotensive Wistar rats. The hypotensive actions of NZ-105 were very slow in onset and long-lasting in all models, e.g., the hypotension by NZ-105 (10 mg/kg, p.o.) reached a peak ( 52 mmHg) at 3 hr and lasted for more than 9 hr in spontaneously hypertensive rats. The hypotensive action in spontaneously hypertensive rats was reproducible after repeated dosing twice a day for 29 days. The hypotensive action after i.v. injection of NZ-105 (0.1 mg/kg) in spontaneously hypertensive rats was also slow in onset (peak time: 10 min) and long-lasting (more than 120 min). The hypotensive potency of NZ-105 was about the same as that of nicardipine, but the increment in heart rate was smaller than in the case of nicardipine. Both NZ-105 and nicardipine showed diuretic and natriuretic actions in spontaneously hypertensive rats. After repeated administration, these actions of NZ-105 were unchanged, whereas those of nicardipine were reduced. These results suggest that NZ-105 is a useful antihypertensive drug with concomitant diuretic effects. PMID- 2241415 TI - Effect of N-acetylneuraminic acid on respiratory tract secretion and inflammation in the bronchitic rabbit. AB - Long-term exposure of rabbits to SO2 gas caused the following changes in the respiratory tract system: decreases in the respiratory rate and pO2 blood level; an increase in the viscosity of sputum associated with increases in protein, unsaturated phosphatidylethanolamine and sphingomyelin; subacute rhinitis, tracheitis and multiple bronchopneumonia. Pretreatment with repeated administrations (inhalations) of N-acetylneuraminic acid remarkably prevented these inflammatory changes. The significance of this finding is discussed. PMID- 2241416 TI - Effect of saline cathartics on the adsorption of sulphamethoxazole to activated charcoal. AB - The effect of added saline cathartics (sodium sulfate and magnesium sulfate) on the in vitro adsorption of sulphamethoxazole to activated charcoal was determined. Sulphamethoxazole, at 0.00125, 0.0025 and 0.005 mg/ml, had a 56.77 to 91.70 per cent adsorption to 50 mg and 200 mg activated charcoal. As the concentration of the activated charcoal was increased from 50 mg to 1000 mg, there was an increase in the amount of sulphamethoxazole adsorbed at 0.125, 0.25 and 0.5 mg/ml. The amount of sulphamethoxazole (0.125-0.5 mg/ml) adsorbed ranged from 10.33 to 83.67 per cent with a B50 value of 472.33 mg. At 7.5 mg/ml, the common saline cathartics sodium sulfate and magnesium sulfate decrease the B50 values to 274.65 and 41.20 mg, respectively. Both saline cathartics enhanced adsorption of sulphamethoxazole to activated charcoal. PMID- 2241417 TI - Effects of a perfluorochemical emulsion on L-tryptophan binding by human albumin. AB - The effect of a perfluorochemical emulsion on ligand binding by human albumin was studied using a site specific approach. L-tryptophan was used as a marker for binding to site II on human albumin. Centrifugation, followed by supernatant ultrafiltration at ambient room temperature, was employed to determine the per cent tryptophan free. The partitioning of tryptophan from pH 7.4 phosphate buffer into the pure perfluorochemical liquids was insignificant. Tryptophan was not significantly bound by the perfluorochemical emulsion droplets. Binding of tryptophan by buffer dilutions of human albumin demonstrated that, at the tryptophan concentrations examined, human albumin concentration had little effect on the per cent tryptophan free. Tryptophan binding by mixtures of the perfluorochemical emulsion and human albumin showed that, at sufficiently high concentrations of the perfluorochemical emulsion, one or more of the emulsion components is responsible for the direct and/or indirect displacement of human albumin-bound tryptophan. The individual perfluorochemical emulsion components were studied for their effects on the binding of tryptophan by human albumin. Results showed that oleic acid and, to a very small degree, Pluronic F-68, were responsible for the displacement of human albumin-bound tryptophan. PMID- 2241418 TI - Hypoglycemic action and disposition of gliclazide in normal and analbuminemic rats. AB - The hypoglycemic action and disposition of gliclazide, an oral antidiabetic drug, was investigated in normal and analbuminemic rats. Orally administered gliclazide exhibited a stronger hypoglycemic action in analbuminemic rats than in normal rats. However, the plasma concentration of the drug in the mutant was much lower than that in the normal. This apparent discrepancy may be clarified by measuring the plasma concentration of unbound gliclazide. Analbuminemic rats gave larger values for the total body clearance and steady state volume of distribution of gliclazide than normal rats. The biliary and urinary excretion rates of radioactivity after intravenous bolus administration of [3H]-gliclazide were much greater in the mutant than in the normal. The binding of gliclazide to serum in analbuminemic rats was much lower than that in normal rats. Furthermore, the radioactivities of some tissues after oral administration of [3H]-gliclazide were found to be significantly higher in the mutant than in the normal. These results clearly indicate that albumin plays an important role in the hypoglycemic activity and disposition of gliclazide in rats. PMID- 2241419 TI - The effects of a new cholinolytic--8018--and its optical isomers on the central muscarinic and nicotinic receptors. AB - 3-(2'-phenyl-2'-cyclopentyl-2'-hydroxyl-ethoxy)quinuclidine (8018), a new cholinolytic, is a racemic tertiary amine with two chiral carbonic atoms. It has 4 optical isomers whose absolute configurations are RR', SR', RS' and SS'. These compounds showed potent pharmacological activity, blocking both central muscarinic and nicotinic receptors. Central muscarinic receptors, rather than nicotinic receptors, have a stereoselective specificity to these compounds. The R configuration of both substituted alkoxyl and alkalinic alcohol parts is more suitable to the stereostructure of the binding site of muscarinic receptors than the S configuration. These compounds can prevent soman-induced electroencephalographic seizures in rats by both their central M- and N cholinolytic actions. PMID- 2241420 TI - Autoradiographic localization of peripheral [3H]-hydergine binding sites. AB - The anatomical distribution of the ergot derivative [3H]-hydergine (co-dergocrine mesylate) was analyzed by the use of an in vitro autoradiographic technique on frozen sections of rat heart, mesenteric and renal arteries, adrenal gland and kidney. In the heart, [3H]-hydergine was bound by atria and by myocytes of ventricles. In the arterial wall, the drug was bound primarily by the adventitia, by the adventitia-media border and by the intimal layer. The density of adventitial and adventitial-medial binding sites has an inverse relation with the diameter of mesenteric or renal vessels. In the adrenal gland, [3H]-hydergine was bound primarily by the medulla and, in lesser amounts, by the zona glomerulosa. In the kidney, the drug was localized within the arterial tree as well as in cortical tubules and in medullary collecting tubules. The above findings suggest that [3H]-hydergine is bound by various structures involved in the regulation of cardiovascular homeostasis. Interaction with these sites probably accounts for the antihypertensive action of hydergine. PMID- 2241421 TI - Mechanisms of hexamethonium-induced tetanic fade in the isolated rat muscle. AB - The action of hexamethonium on neuromuscular transmission was investigated on the rat extensor digitorum longus muscle in vitro. Hexamethonium (5 x 10(-4) M) induced a complete fade of the tetanic contraction while leaving the twitch unaffected. At the same concentration, hexamethonium induced a significant decrease in the amplitude of the endplate potentials evoked at 50 and 100 Hz. Additionally, hexamethonium (5 x 10(-4) M) significantly increased the tetanic rundown of the endplate potential trains evoked at 100 Hz. The former effect was mainly the result of a frequency-independent decrease in the quantal size of the endplate potentials. This decrease seemed to be due to a postsynaptic blocking action of hexamethonium. The increase in tetanic rundown was due to a presynaptic action of hexamethonium. Such an action led to a frequency-dependent decrease in the quantal release of transmitter during repetitive stimulation of the motor nerve. It is concluded that both pre- and postsynaptic actions are necessary for hexamethonium to induce tetanic fade without affecting the twitch; and that, if it is accepted that the presynaptic action of hexamethonium is exerted on presynaptic receptors, these are not of the ganglionic type since the presynaptic effect of hexamethonium was less pronounced than the postsynaptic one. PMID- 2241422 TI - Metoclopramide on rat phrenic hemidiaphragm. AB - The effect of metoclopramide on skeletal muscle and its neurotransmission was studied employing innervated and denervated rat diaphragm. Metoclopramide, at concentrations from 0.035 to 0.14 mM, inhibited the twitch contractions of rat diaphragm stimulated either directly or indirectly. Inhibition was greater in indirectly stimulated preparations, at a given concentration of metoclopramide, than in directly stimulated preparations. Inhibition of indirect twitch by metoclopramide could be intensified by raising the concentration of magnesium chloride, but was unaffected by physostigmine or d-tubocurarine. Metoclopramide also inhibited the submaximal contractures of denervated diaphragm elicited by potassium chloride and acetylcholine. In calcium-free physiological solution, metoclopramide inhibited the caffeine-induced contractures of denervated diaphragm as a function of its concentration. It is suggested that metoclopramide possesses a calcium antagonistic action in the rat diaphragm. PMID- 2241423 TI - Effect of diisopropylfluorophosphate and atropine or mecamylamine on acetylcholine levels in the central nervous system of the rat. AB - The effect on acetylcholine levels caused by diisopropylfluorophosphate, either alone or in combination with atropine or mecamylamine, has been studied in the olfactory brain, medulla pons and cortex of the rat. At sublethal doses (0.25 and 0.5 mg/kg), diisopropylfluorophosphate reduced the acetylcholine levels. This effect was completely antagonized by atropine in the medulla pons and by mecamylamine in the medulla pons, olfactory brain and partly in the cortex. These observations suggest that the reduction of acetylcholine levels at low doses of diisopropylfluorophosphate is mediated by a muscarinic system in the medulla pons and by a nicotinic system in the medulla pons, the olfactory brain and also, in part, in the cortex. PMID- 2241424 TI - Vasoactive intestinal polypeptides induce guinea-pig ileum contraction by causing release of endogenous acetylcholine. AB - Two vasoactive intestinal polypeptide (VIP) analogues were observed to induce a concentration-dependent contraction of guinea-pig ileum, which was blocked by atropine but not by tubocurarine. The analogue from guinea-pig, VIP [VIP(gp)], was the most potent inducer of ileum contraction, followed by human-porcine-rat VIP [VIP(hpr)], which differs from VIP(gp) by 4 nonpolar amino acid substitutions. VIP(1-15), composed of only the first 15 of the 28 amino acids of VIP(hpr), was without effect. The relative potency of VIP(gp), VIP(hpr), and acetylcholine was 50 to 100 times more potent in inducing contraction in ileums of which the acetylcholinesterase was inactivated by paraoxon than in the controls. The VIP analogues which induced contraction of ileum also induced secretion of endogenous acetylcholine. The secreted acetylcholine was quantified by high-performance liquid chromatography using electrochemical detection and an immobilized-enzyme column consisting of choline oxidase and acetylcholinesterase. The induction of ileum contraction by VIP(gp), from 10nM to 1 microM VIP, was correlated with the amounts of ACh secreted from ileum. VIP(hpr) induced less acetylcholine secretion than VIP(gp), and was also less potent in causing ileum contraction. VIP(1-15), even at 10 microM, caused neither acetylcholine release nor ileum contraction. PMID- 2241425 TI - Comparative studies of intracerebroventricularly administered cysteamine and pantethine in different behavioral tests and on brain catecholamines in rats. AB - In a passive avoidance test, intracerebroventricular administration (post-trial treatment) of the somatostatin-depleting compound cysteamine decreased the avoidance latency of the rats in a dose-related manner, while the effect of pantethine (which is metabolized to cysteamine) was less pronounced. In open field studies, both compounds decreased the motor activity (ambulation, rearing) of the animals 15 min after the injection followed by a subsequent recuperation of the locomotor depression. Following pantethine, the ambulation increased during the later tests (60 min, 240 min, 24 hr). Cysteamine decreased the noradrenaline and increased the dopamine and dihydroxyphenyl acetic acid content in the hypothalamus, whereas the effects of pantethine were less expressed. Both compounds slightly decreased the striatal noradrenaline and increased the dihydroxyphenyl acetic acid levels at 15 and 60 min after administration. However, contrary to pantethine, 4 hr after treatment with cysteamine, there was a decrease in dihydroxyphenyl acetic acid concentration in this brain region. These findings suggest that both pantethine and cysteamine attenuate passive avoidance latency after intracerebroventricular treatment. The different efficiency of pantethine and its metabolite cysteamine might be connected to the low pantetheinase activity of the brain tissue; however, some direct effects of pantethine cannot be excluded. The different effects of the two compounds on the open-field activity are possibly associated with the diverse effects of the compounds on the striatal dopaminergic neurotransmission. PMID- 2241426 TI - Effects of loreclezole on metrazol-induced phenomena in developing rats. AB - A potential antiepileptic drug, loreclezole, was studied in rats of 7, 12, 18, 25 and 90 days old. Metrazol-induced motor phenomena served as a model. Loreclezole did not consistently influence isolated myoclonic jerks or minimal metrazol seizures (predominantly clonic with preserved righting ability). Major metrazol seizures, i.e., generalized tonic-clonic seizures, were suppressed by loreclezole in a dose-dependent manner in all age-groups, except in the 7 day old group where outlined changes did not reach statistical significance. Severity of seizures was significantly diminished at all developmental stages studied. Loreclezole exhibits nearly the same profile of action as phenytoin and carbamazepine in this model. PMID- 2241428 TI - Methyl parathion acute toxicity: prophylaxis and therapy with memantine and atropine. AB - Male rats administered with a single i.p. dose of 5 mg/kg methyl parathion, showed the toxic signs of hypercholinergic (anticholinesterase) activity with maximal severity, including muscle fasciculations and convulsions within 15 to 30 min, persisting for about 2 hr. The time course of acetylcholinesterase activity in discrete brain regions (cortex, stem, striatum and hippocampus), heart and hemidiaphragm, indicated its maximal depression during 30 to 60 min after administration of methyl parathion. At this time, a marked reduction in carboxylesterase activity was also evident both in neuronal and nonneuronal tissues, suggesting a tremendous binding to nonacetylcholinesterase serine sites. Pretreatment with memantine hydrochloride (18 mg/kg, i.p.) 30 min, and atropine sulfate (16 mg/kg, i.p.) 15 min before methyl parathion administration, completely prevented the expected toxic signs and significantly (P less than 0.01) attenuated the induced inhibition of acetylcholinesterase. When given therapeutically, this combined treatment completely reversed the clinical evidence of methyl parathion toxicity within 10 to 15 min and markedly reduced the acetylcholinesterase inactivation. These results suggest that memantine may counteract the acute methyl parathion toxicity by (a) protection of acetylcholinesterase from inhibition, (b) rapid reactivation of inhibited acetylcholinesterase and (c) rapid bioelimination of methyl parathion, in addition to cholinolytic effects of atropine sulfate. PMID- 2241427 TI - Proteoglycans in bones of streptozotocin-induced diabetic rats. AB - Insulin seems to regulate the biosynthesis of proteoglycans in some tissues such as growth plate and glomeruli. The present investigation was undertaken to assess the ex vivo influence of insulin on proteoglycan metabolism in bones. Mandible and femur bones were used. Xiphoid cartilage was used as a control tissue of high glycosaminoglycan content. Diabetes was induced by 0.12 mg/g b.w. streptozotocin in male Sprague-Dawley rats, a number of which was treated with insulin (1 I.U./100 g b.w.) for 6 days. As compared with control animals, diabetic rats exhibited a decreased [35S]sulfate uptake as well as a shift to the right in Sephacryl S-500 chromatography. In addition, they showed lower density of proteoglycans in sucrose gradient and shorter glycosaminoglycan side chains in Sephadex G-200 chromatography. These changes were partly reversed by insulin. PMID- 2241429 TI - Antagonism of acetylcholine action in guinea-pig tracheal smooth muscle and epithelium by pirenzepine, 4-DAMP and atropine. AB - Acetylcholine-induced guinea-pig tracheal smooth muscle contraction and epithelium-derived relaxant factor release were evaluated using guinea-pig open tracheal rings and rat anococcygeus muscle bioassay to get insight into the participation of muscarinic receptor subtypes in these responses. There was a significant difference between the two pA2 values obtained in contraction and relaxation experiments for pirenzepine, but no difference was found either for atropine or for 4-DAMP. This difference seems to be due to the participation of M1-receptors in smooth muscle contraction. PMID- 2241430 TI - Electrocardiographic changes induced by levamisole hydrochloride in the rat. AB - The acute electrocardiographic effects of levamisole hydrochloride (2, 6, 10 and 20 mg/kg) were examined in the anaesthetized rat. Levamisole caused a fall in heart rate which was greatest at 20 mg/kg. The P-R interval was increased and was longest during the first 2 min after administration of the drug. The Q-T interval, corrected for rate (QTc), was little affected but at 20 mg/kg, 2 of the 5 rats presented 58% and 94% increases over the value at equilibration. Widening of the QRS complex did not occur at 2 and 6 mg/kg, but at 10 and 20 mg/kg a marked widening occurred in 1 out of 4 and 3 out of 5 rats, respectively. Cardiac dysrhythmias occurred even at 2 mg/kg. Severe bradycardia from sino-atrial depression or from A-V block, including Mobitz Type II A-V block, as well as ventricular tachycardia and fibrillation were observed. PMID- 2241431 TI - Effects of pimobendan and UD-CG-212 CL on calcium exchange and contraction in isolated rabbit aorta. AB - The effects of pimobendan and its O-demethylmetabolite UD-CG-212 CL on contractile responses and transmembrane Ca fluxes were studied on rabbit isolated aortic rings. Both pimobendan and UD-CG-212 CL (10(-7) M-5 X 10(-4) M) concentration-dependently inhibited the contractile responses induced by KCl (80 mM) and noradrenaline (10(-6) M). This inhibitory effect was observed when these compounds were added either before or after the induced contractions, but was reduced in aortic rings after removal of endothelium. Pimobendan and UD-CG-212 CL shifted the concentration-response curve to noradrenaline downwards and to the right and inhibited the contractile responses elicited by addition of Ca (1-5 mM) to Ca-free high K solution. Pimobendan also inhibited the contractile responses induced by caffeine (20 mM) in aortic rings incubated in normal or in Ca-free medium. At 5 X 10(-4) M, pimobendan inhibited 45Ca influx in resting as well as in aortic rings stimulated by high K and noradrenaline and increased the rate of 45Ca efflux in nonstimulated aortae. It is concluded that pimobendan and its O dimethylmetabolite UD-CG-212 CL exhibit vasodilator properties in the isolated rabbit aorta by their acting at multiple sites of action, thus decreasing the availability of Ca required for smooth muscle activation. PMID- 2241432 TI - Decreased modulation by endothelium of noradrenaline-induced contractions in aorta from stroke-prone spontaneously hypertensive rats. AB - Influences of endothelium on contractions of aortic ring preparations from 15 to 17 weeks old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto rats (WKY) were compared. Noradrenaline-induced contraction was potentiated by endothelium removal; the potentiation was greater in the WKY aorta. Noradrenaline (10(-5) M) induced a biphasic contraction in endothelium intact WKY aorta, while endothelium-intact SHRSP aorta or endothelium-removed preparations of both strains showed a monophasic sustained contraction. The tension changes in high-K-induced contracture of the endothelium-intact preparation was less pronounced in both WKY and SHRSP aortae. The relaxation by acetylcholine (10(-5) M) of endothelium-intact aortae, precontracted with noradrenaline (5 X 10(-7) M), amounted to 78% in the WKY and to 44% in the SHRSP preparation. In endothelium-removed aortae, sodium nitroprusside induced a comparable relaxation in both WKY and SHRSP preparations. These results indicate that the endothelium plays an important role in controlling the noradrenaline induced contraction and that the lower influence of endothelium in the SHRSP aorta is most likely due to a decreased activity of this endothelium. PMID- 2241433 TI - The experience of house officers. An area deserving further study. PMID- 2241435 TI - Empiric treatment of fungal infections in the neutropenic host. Review of the literature and guidelines for use. AB - Persistent fever that is refractory to broad-spectrum antibacterials is common in neutropenic patients undergoing induction chemotherapy of acute leukemia. Clinical experience suggests that many of these patients are infected with fungi. Until recently, data supporting the role of empiric antifungal therapy in this setting were limited to small groups of patients or postmortem reports. Evolving evidence in larger patient populations supports data from smaller series: febrile neutropenic patients who have failed to respond to a 4- to 7-day course of broad spectrum antibacterials may benefit from the early initiation of antifungal therapy. Patients with fungal colonization or pulmonary infiltrates and adult patients who have not received previous fungal prophylaxis may especially benefit from the early use of antifungal drugs. Amphotericin B has been the "gold standard" for empiric antifungal therapy, although the newer azoles may be useful in certain situations. PMID- 2241434 TI - Caring for medical students as patients. PMID- 2241436 TI - Systemic therapy in metastatic colorectal cancer. AB - Fluorouracil-based chemotherapy regimens have been utilized in metastatic colorectal cancer for more than 30 years. Early attempts at defining an optimal treatment schedule and use in combination with other drugs failed to significantly improve results. In contrast, the clinical effectiveness of fluorouracil has been improved by continuous infusion administration and modulation with folinic acid. Both approaches have increased the response rate compared with results achieved with traditional bolus schedules; the effect on survival has been less significant. Unfortunately, expense and, in some instances, toxicity have also been increased, which detracts from their overall usefulness. Clinical studies that evaluate fluorouracil chemotherapy in combination with biological-response modifiers are ongoing and will be areas of intense research during the next few years. PMID- 2241437 TI - The on-call experience of interns in internal medicine. Medical Education Task Force of Henry Ford Hospital. AB - As part of an effort to examine the structure and content of our residency program in internal medicine, we assessed interns' activities on call to identify problems with workload scheduling, supervision, or learning. Eleven interns were observed continuously during a 34-hour on-call period. Interns averaged 5.6 hours at the bedside, with 57 minutes of that time under direct supervision of a resident or attending physician. Nearly half of new patient examinations continued after midnight despite a special night admission team that evaluated all patients admitted after 11 pm. The interns averaged 21 beeps per 30 hours. They slept an average of 2.5 hours with two interruptions. They read about their patients an average of 4 minutes during the 34-hour period. Most supervision was away from the bedside (82/139 minutes). Bedside supervision occurred predominantly during rounds (45/57 minutes). Attending physicians averaged only 12 minutes of bedside interaction with the intern. Many of these findings were unanticipated. Structural defects in the training program were defined and are being addressed. Other training programs should consider similar analyses before making fundamental changes. PMID- 2241438 TI - Misdiagnosis in patients with amyotrophic lateral sclerosis. AB - To confirm our impression that a high percentage of patients with amyotrophic lateral sclerosis are initially misdiagnosed, we reviewed records of 33 patients with a definitive diagnosis of amyotrophic lateral sclerosis seen over 10 years. Fourteen patients (43%) were initially misdiagnosed. Mean time to correct diagnosis was significantly greater for the misdiagnosed group (16.0 +/- 9.3 months) than for the rest of the patients (7.6 +/- 4.1 months). Two of three patients with an initial symptom of dyspnea were misdiagnosed. Three patients underwent laminectomies because of misdiagnosis. Age, stage of disease, and unusual presenting symptoms were not identified as causes of misdiagnosis. Most likely causes were physicians' failure to consider the diagnosis and lack of familiarity with the common clinical presentations of amyotrophic lateral sclerosis. Earlier diagnosis of amyotrophic lateral sclerosis may help prevent medical mismanagement and may benefit patients both medically and psychologically. PMID- 2241439 TI - Syncope and presyncope associated with probable adverse drug reactions. AB - The purpose of this study was to determine whether syncope and presyncope were associated with drug therapy in 70 patients referred to a tertiary care ambulatory clinic. Drug use information was obtained, validated, and classified by its potential to cause syncope and presyncope. Utilizing a standardized adverse drug reaction algorithm, nine (13%) of the 70 patients were rated as having probable drug-induced syncope and presyncope events. Overall, 12 medications were implicated. Patients with probable adverse drug reactions were older, and taking more medications, or taking an antihypertensive. Seven of the nine patients with probable adverse drug reactions were previously classified as having syncope of unknown origin after their initial clinic evaluation. Syncope and presyncope are commonly associated with adverse drug reactions, especially in the elderly and those taking multiple medications. PMID- 2241440 TI - The relationship between sex hormones and high-density lipoprotein cholesterol levels in healthy adult men. AB - The objective of this study was to clarify the complex and uncertain relationship between endogenous sex hormones and high-density lipoprotein (HDL) cholesterol levels in healthy men. Fifty-five healthy adult men were consecutively recruited from an ongoing cross-sectional study of cardiovascular disease risk factors from a lipid research clinic at the University of Washington, Seattle. Subjects receiving medication were excluded. Multiple linear regression analysis identified several factors that correlated highly significantly with HDL cholesterol levels, including alcohol intake; frequency of strenuous exercise; age; levels of total cholesterol, low-density lipoprotein cholesterol, and triglyceride; and carbohydrate intake. Nearly 80% of the heterogeneity in HDL cholesterol levels could be accounted for by these factors. Despite finding significant correlations with factors known to influence HDL cholesterol levels, no correlation with estradiol level, testosterone level, or the ratio of estradiol to testosterone levels was apparent. In conclusion, endogenous sex hormones do not appear to influence HDL cholesterol levels in healthy adult men. Alternatively, a large proportion of the heterogeneity in HDL levels in this group of men can be accounted for by environmental factors. The disparity between this conclusion and others may be partially due to differences in accounting for these confounding variables. PMID- 2241441 TI - Health, homelessness, and poverty. A study of clinic users. AB - When seeking medical care, homeless persons often turn to health centers that were designed to treat the poor who have homes. To provide for effective medical care, personnel in such facilities need to know how the health care needs of the homeless are different from those of other clinic users. To compare the physical health of these two groups, we conducted a health survey and screening physical examination of 464 patients who attended the general adult and homeless clinic sessions of one of the main neighborhood health centers in Los Angeles County, California. As compared with the poor who have homes, homeless persons were more likely to have dermatological problems (32% vs 21%), functional limitations (median, 2 vs 0 per person), seizures (14% vs 6%), chronic obstructive pulmonary disease (21% vs 12%), social isolation, serious vision problems (22% vs 12%), foot pain, and grossly decayed teeth (median, 1 vs 0 per person). We conclude that to care more optimally for homeless adults, health centers must pay attention to their functional disabilities, substance abuse, skin abnormalities, vision impairment, dental problems, and foot problems. PMID- 2241442 TI - The influence of physician specialty on housecalls. AB - Despite growing numbers of frail elderly, physicians make housecalls infrequently. We surveyed 1000 primary care physicians from Virginia regarding their attitudes and knowledge about housecalls, and 389 completed questionnaires (response rate, 52%): 185 family physicians, 36 general practitioners, 101 general internists, and 63 subspecialists. Despite similar proportions of homebound patients and practice demographics, family physicians (69%) and general practitioners (63%) were significantly more likely than either internists (53%) or subspecialists (37%) to make routine housecalls. Although all four groups thought the fee was rarely a motivation, internists and subspecialists suggested larger increases. Also, internists and subspecialists were less likely than family physicians or general practitioners to increase housecalls with increased payment. Internists and subspecialists also were more likely than family physicians or general practitioners to report that housecalls were often unnecessary, not "enjoyable," "inefficient," and unimportant. While improved reimbursement may lead to increased housecalls by family physicians, future strategies should include efforts to change internists' attitudes. PMID- 2241443 TI - Epidemiologic features of asymptomatic cerebral infarction in patients with nonvalvular atrial fibrillation. AB - We performed unenhanced computed tomographic scans on 141 asymptomatic patients with nonvalvular atrial fibrillation. Thirty-six patients (26%) had hypodense areas consistent with cerebral infarction. The majority of these were small deep infarcts, seen in 29 patients (21%), but 13 patients (9%) had cortical or large deep infarctions. Twelve patients had more than one infarct on computed tomographic scan. Increasing age and increased left atrial diameter were the only clinical features associated with asymptomatic infarction. Patients older than 65 years with a left atrial diameter greater than 5.0 cm (n = 23) had a 52% prevalence of asymptomatic infarction. Patients younger than 65 years with a left atrial diameter less than 5.0 cm (n = 38) had an 11% prevalence of silent infarction. Patients with only one of these risk factors (n = 72) had a 24% prevalence of silent infarction. Infarction was more common in those with chronic (34%) as opposed to intermittent (22%) nonvalvular atrial fibrillation, but this difference was not significant. Hypertension, diabetes, duration of atrial fibrillation, congestive heart failure, history of myocardial infarction, and echocardiographic evidence of left ventricular dysfunction were not associated with asymptomatic infarction. A history of hypertension was present in only 35% of our patients with small-deep asymptomatic infarction, similar to the percentage in patients without stroke. Asymptomatic cerebral infarction is common in nonvalvular atrial fibrillation. The association with enlarged left atria and the lack of correlation with major cerebrovascular risk factors suggests a cardioembolic mechanism. Further study is needed to determine the functional and prognostic significance of these strokes. PMID- 2241444 TI - Seroprevalence of Helicobacter pylori in Seventh-Day Adventists and other groups in Maryland. Lack of association with diet. AB - To evaluate the possible role of diet in the transmission of Helicobacter pylori, we compared H pylori seroprevalence among Seventh-Day Adventists (who are vegetarian and abstain from alcohol, caffeine, and meat; n = 94) and two non Seventh-Day Adventist control groups (n = 168). With the use of an enzyme-linked immunosorbent assay H pylori antigen prepared in a French pressure cell, we found no difference in seroprevalence among these groups; however, seropositivity strongly correlated with age and black race. PMID- 2241445 TI - Profile of bronchospastic disease in Puerto Rican patients in New York City. A possible relationship to alpha 1-antitrypsin variants. AB - A high prevalence of asthmalike symptoms was noted among patients of Puerto Rican descent attending Beth Israel and North Central Bronx Medical Centers in New York City, as compared with other ethnic groups. An evaluation of family and medical histories, pulmonary function data, and alpha 1-antitrypsin phenotypes was undertaken in such Puerto Rican patients and control subjects without asthma. The patients showed a higher proportion of MS and MV phenotypes. All the patients in both MM and variant phenotype groups, with the exception of four MM patients, had features indicative of asthma, with labile airway obstruction, and elevated serum immunoglobulin E and eosinophil levels. The latter was significantly higher in the patients with variant phenotypes than in MM patients. Patients with alpha 1 antitrypsin variants also had much shorter smoking histories as compared with the MM group, and all reported histories of asthma in first-degree relatives, as compared with 66% among the MM patients. We conclude that there is an increased incidence of asthma among Puerto Ricans in New York City, and that the antitrypsin variant phenotypes (specifically S and V) play a role in this incidence and its expression. PMID- 2241446 TI - Medical comorbidity of major depressive disorder in a primary medical practice. AB - Despite much speculation about the relationship between depression and medical comorbidity in primary care settings, few investigators have examined this issue empirically. Using a two-stage screening procedure, we assessed 618 patients aged 18 to 64 years in an academic general medicine clinic. Forty-one patients (6.6%) suffered from a current episode of major depressive disorder (MDD). We compared this group with a 20% random sample of nondepressed patients. While patients with MDD were younger (mean age, 41.1 vs 47.2 years), they were assessed by the Duke University Severity of Illness Scale as having more severe medical illness. Patients with MDD were more likely to have malignant tumors and "ill-defined conditions" than nondepressed patients. The 18 patients with MDD (44%) who were correctly diagnosed by their physicians had less severe medical illness than those whose depression was clinically undetected. A logistic regression model predicting MDD group membership included female gender, younger age, higher Duke University Severity of Illness Scale score, and more frequent inactive ill defined diagnoses. These findings are consistent with assertions: (1) patients with MDD have more physical illness than nondepressed patients and/or (2) somatic symptoms and disability caused by MDD add to the burden of physical illness. PMID- 2241448 TI - Acute autonomic neuropathy. Two cases and a clinical review. AB - Acute autonomic neuropathy is an uncommon syndrome, usually affecting healthy young people. Presentation is often dramatic and initial misdiagnosis is common. We describe two young women with acute autonomic neuropathy who presented with gastrointestinal involvement heralding widespread dysautonomia and review 26 additional cases of acute autonomic neuropathy from the English language literature. Acute autonomic neuropathy can be primarily cholinergic without orthostatic hypotension (26%) or pandysautonomic (74%) involving sympathetic adrenergic functions. Onset has been temporally related to viral syndromes in 20% of cases, with autonomic deficits usually evolving over 1 to 3 weeks. Gastroparesis (69%) and syncope (12%) are frequent presenting complaints. Spinal fluid protein levels are often (75%) elevated in pandysautonomic subtypes. Prolonged and incomplete recovery is the rule (60%), with persistent gastroparesis and orthostatic hypotension. Other specific diseases that occasionally mimic acute autonomic neuropathy include botulism, porphyria, amyloidosis, and paracarcinomatous neuropathies. Acute autonomic neuropathy shares several clinical features with acute idiopathic polyneuropathy (Guillain Barre syndrome), suggesting an immune-mediated pathogenesis. PMID- 2241447 TI - Diagnostic testing and return visits for acute problems in prepaid, case-managed Medicaid plans compared with fee-for-service. AB - Enrollment of Medicaid recipients into capitated, case-managed systems of health care has been advocated as a means to control costs. We studied the effect of such systems on care for urinary tract infection (UTI), pelvic inflammatory disease, and vaginitis among women enrolled in Aid to Families with Dependent Children in capitated demonstration programs in Santa Barbara County, California, and Jackson County, Missouri (prepaid), compared with similar but fee-for-service (FFS) counties in Ventura County, California, and St Louis, Mo. Structured abstracts were performed on 2382 outpatient charts with one of the three conditions in 1985. The proportion of cases with UTI in which a urine culture was obtained was similar in Santa Barbara (prepaid) and Ventura (FFS), 47% vs 46%, but greater in Jackson County (prepaid) than St Louis (FFS), 58% vs 32%. The proportion of cases with return visits for a UTI was: Santa Barbara (prepaid), 40%; Ventura (FFS), 33%; Jackson (prepaid), 72%; and St Louis (FFS), 53%. The proportion of patients with pelvic inflammatory disease with cervical cultures for gonorrhea as Santa Barbara (prepaid), 81%; Ventura (FFS), 52%; Jackson (prepaid), 86%; and St Louis (FFS), 61%. The proportion of women returning for follow-up after pelvic inflammatory disease was similar across all counties at 40% and 50%. The number of office diagnostic tests performed for vaginitis was greater in both demonstration counties. These data do not demonstrate any diminution in either diagnostic testing or follow-up visits for three common ambulatory problems in a Medicaid population enrolled in a capitated, case managed system, with some trends for more care in the demonstration sites. PMID- 2241449 TI - Sulfadiazine crystalluria revisited. The treatment of Toxoplasma encephalitis in patients with acquired immunodeficiency syndrome. AB - Toxoplasma gondii encephalitis is an important opportunistic infection in the acquired immunodeficiency syndrome, estimated to occur in 20,000 to 40,000 patients with acquired immunodeficiency syndrome in the United States by 1991. The combination of sulfadiazine and pyrimethamine is regarded as the treatment of choice. Acute renal failure due to crystal deposition in the urinary tract was well described 30 to 40 years ago and is likely to resurface as a clinical entity if appropriate prophylactic measures are not taken. We describe two cases of sulfadiazine-induced crystalluria and renal failure in patients with acquired immunodeficiency syndrome, review the pertinent literature, and discuss the pathogenesis. Recommendations are made for the prophylaxis and treatment of sulfadiazine-related renal toxic reaction. Physicians using this "new" drug must be aware of the potential danger of sulfonamide-induced injury to the urinary tract. PMID- 2241450 TI - Pheochromocytoma presenting as rhabdomyolysis and acute myoglobinuric renal failure. AB - We report the case of a previously healthy young woman who presented with the sudden onset of rhabdomyolysis and myoglobinuric renal failure, requiring hemodialysis for 3 weeks. Common causes of rhabdomyolysis were ruled out; as renal function returned, severe hypertension was noted and a pheochromocytoma was diagnosed. We suggest that pheochromocytoma causes rhabdomyolysis and myoglobinuria via catecholamine-mediated vasoconstriction and skeletal muscle ischemia. PMID- 2241451 TI - Hyperammonemic encephalopathy in urinary diversion with urea-splitting urinary tract infection. AB - We present two cases of hyperammonemic encephalopathy secondary to urea-splitting urinary tract infection with urinary diversion. One patient had a ureterosigmoidostomy, the other an ileal loop diversion. Neither patient had significant underlying liver disease, but both had considerable muscle atrophy that may have predisposed them to develop hyperammonemia. Medical therapy did not provide long-term control of symptoms. In both cases, hyperammonemic encephalopathy resolved after revision of their urinary diversions. The probable mechanism of the metabolic derangements produced by urea-splitting urinary tract infections is reviewed. We suggest that patients with urinary diversion who develop hyperammonemic encephalopathy secondary to a urea-splitting urinary tract infection be treated with surgical revision of the urinary system to improve drainage and decrease bowel contact time. PMID- 2241452 TI - Recurrent meningitis in a patient with congenital deficiency of the C9 component of complement. First case of C9 deficiency in Europe. AB - We describe the first cases, to our knowledge, of C9 deficiency in Europe that were detected in a Swiss family, of which two members--one with a complete deficiency and the other with approximately half-normal C9 levels--experienced bacterial meningitis. The index patient, a 56-year-old white man with a history of purulent meningitis at the age of 23 years, presented with an acute meningococcal meningitis. No impairment of cellular immunity or immunoglobulin deficiency could be found. Complement assays showed a complete deficiency of the C9 component, while the other individual component levels were normal and the hemolytic activity (measured using the CH50 assay) was only slightly reduced. A family study revealed complete C9 deficiency in the patient's healthy brother and half-normal C9 concentrations in his sister, his son (who also had experienced an episode of bacterial meningitis), and his niece, consistent with an inherited C9 deficiency. This first case of recurrent meningitis in a white patient with complete C9 deficiency suggests that this complement defect may also be a risk factor for bacterial, especially neisserial, infections. PMID- 2241453 TI - Thyrotoxicosis induced by topical iodine application. AB - We describe an elderly man who was admitted with congestive cardiac failure and found to have thyrotoxicosis. He did not have goiter, and he had normal radioiodine uptake in his neck. Serum iodine levels were elevated, explaining the lack of increase in radioiodine uptake in the thyroid gland. He had multiple pressure sores, which were treated with povidone-iodine (Betadine) soaks. Biochemical data were consistent with Graves' disease unmasked by topical iodine application. Povidone-iodine soaks are commonly used in decubitus ulcer care and warrant special attention in patients with preexisting thyroid disorders. We have reviewed the literature on this unusual complication. PMID- 2241454 TI - Treatment of severe reactive hypoglycemia with a somatostatin analogue (SMS 201 995). AB - Reactive (or postprandial) hypoglycemia can sometimes represent a severe disorder refractory to conventional therapeutic measures. We present in this first individual trial, to our knowledge, that the administration of a somatostatin analogue (SMS 201-995) may alleviate the severity of complaints and does not appear to be diabetogenic. The effects of the somatostatin analogue were documented in a 5-hour oral glucose tolerance test, where not only the glucose induced and C-peptide rise was clearly attenuated, but also the blood glucose concentration did not fall low enough to induce hypoglycemic symptoms. PMID- 2241455 TI - Lovastatin. Warfarin interaction. AB - Two patients who developed hypoprothrombinemia and bleeding due to lovastatin warfarin drug interaction are described. Because of the wider use of lovastatin and warfarin, heightened clinical awareness of this potentially serious interaction must be publicized. Therefore, prothrombin time should be monitored diligently when warfarin is prescribed to patients receiving lovastatin. PMID- 2241456 TI - The Hypertension Prevention Trial. PMID- 2241457 TI - The value of fine-needle aspiration biopsy in nodular thyroid disease. PMID- 2241458 TI - Pulsus paradoxus, cardiac tamponade, and the pericardial 'window'. PMID- 2241459 TI - Inadequate barium enemas in elderly patients. PMID- 2241460 TI - Fine-needle aspiration biopsy of the thyroid. PMID- 2241461 TI - Failure to check references. PMID- 2241462 TI - Indomethacin in the treatment of lithium-induced nephrogenic diabetes insipidus. PMID- 2241463 TI - Less expensive is not always less effective. PMID- 2241464 TI - The effect of oral and parenteral typhoid vaccination. PMID- 2241465 TI - Infections and toxic syndromes from fish and shellfish consumption. PMID- 2241466 TI - [The tasks of psychiatry: the psychiatric experience]. AB - This work pretends to show the necessity of psychiatry of knowing its grounds as medical knowledge in order to do justice to its history and to the concepts that have been traditionally used in the west way of thinking. By the idea of experience it is tried to search in psychopathology the motives of the transformation of psychiatry under the operative concept of 'life world'. The psychiatry tasks shall be those in connection with the development and appropriation of the ontological and methodological implications that the concept of 'life world' involves, always across a psychopathological theory. PMID- 2241467 TI - [Morphology of the posterior colliculus in epileptic hamsters]. AB - In an inbred strain of Golden hamsters with audiogenic seizures, we have studied the collicular participation, planning a morphologic study of posterior colliculus central nucleus. The parameters used have been: number of neurons and glia, neuronal areas and area of all the colliculus. The measurement and the counts have been done in both sides and for to validate the results we have used an A.N.O.V.A.. In the epileptic group, there are a less number of neurons and a major correlation Nucleus/cytoplasm. The left-right correlations are positive for the neurons, while in the control group are for the glia. Although, the number of neurons in the epileptic animals are less, this are more active, which can be related to the participation of the colliculus in the audiogenic seizures. PMID- 2241468 TI - [Interhemispherical study of the activities of aminopeptidases, lactate dehydrogenase and glutamate-oxaloacetate transaminase in the rat brain]. AB - Aminopeptidase activity has been assayed from both soluble and membrane bound fractions in eleven regions of the left and right hemispheres of the rat brain, using L-leucine-2-naphthylamide as substrate. Two other metabolic enzymes, lactate dehydrogenase and glutamate-oxalacetate aminotransferase activities were simultaneously determined in the same areas. When individual zones of the left hemisphere were compared with its corresponding right zones, soluble aminopeptidase activities were significantly higher in left frontal cortex and left hypothalamus than in right frontal cortex and right hypothalamus, respectively. No other significant differences were found neither in the remaining areas nor for the other enzymatic activities between both brain hemispheres. PMID- 2241469 TI - [Syndrome of rostral occlusion of the basilar artery]. AB - Upper occlusion of the basilar artery ("top of the basilar" syndrome) causes ischemics lesions in brainstem, thalamus and occipital and temporal lobes, producing visual, oculomotor and behavioral disorders, with slight motor affectation concomitant. We expose a case with a typical clinical setting and infarctions in thalamus and both occipital lobes with an unusual symmetric distribution. PMID- 2241470 TI - [Reintervention in gliomas: the necessity of nuclear magnetic resonance]. AB - The reoperation of patients with recurrence of cerebral glioma is a technique offering survival with a good quality of life. The accepted criteria are a Karnofski index until reoperation greater than or equal to 70, young age, and a favourable histologic grade of tumor. NMR offers better sensitivity than other neuroimaging techniques for the detection of tumoral extension, local and at a distance, and allows a good tumoral resection. We report a patient with recurrence of a cerebral astrocytoma grade II with the criteria for reoperation, but when we performed NMR a dissemination of the tumor to the posterior fossa was seen, and reoperation was consequently counter-indicated. We discuss the mechanism of the extension of cerebral gliomas, the value of neuroimaging techniques and the role of reoperation in this context. We consider it necessary to perform NMR prior to reoperation in this special group of patients with a cerebral glioma recurrence. PMID- 2241471 TI - [Myotubular myopathy linked to chromosome X. Pathological and clinical case study]. AB - We present a case of X-linked myotubular myopathy in a boy who died neonatally because of respiratory insufficiency. Five biopsy revealed predominance and hypotrophy of type 1 fibres with central nuclei in the majority of them, without perinuclear ATPasa activity. Electron microscopic study corroborated these features and showed the absence of perinuclear myofibres. In the postmortem examination there was no involvement of others organs including the central nervous system. PMID- 2241472 TI - [The subacute and subchronic toxicity of chlorophacinone in Japanese quail (Coturnix c. japonica)]. AB - Accordingly to the subacute toxicity of chlorphacinone to Japanese quail (LC 50: 60 mg/kg feed), the uptake of Delicia-chlorphacinone-baits for several days can be lethal to birds as a matter of principle. A subchronic study resulted in a "no observed-effect-level" of 1 mg chlorphacinon/kg feed. Reproduction is not affected until dose levels which resulted in lethality or are accompanied by physiological changes (coagulability of blood, microcytic anaemia). Increased sensibility of descendants to chlorphacinone cannot be derived from the findings. PMID- 2241473 TI - [The effect of steroid hormone doses after ovariectomy on the peripheral hormone processes and uterine development in gilts. 2. Effects on gilts during early pregnancy]. AB - Experimental studies were conducted into ovariectomized pregnant gilts to establish effects of exogenic hormone administration, with endogenic ovarian steroids excluded, upon uterus and fetus development as well as on hormone levels in blood plasma, endometrium, and allantoic fluid. Hormone concentrations in blood plasma were found to depend clearly on hormone doses applied after ovariectomy to preserve pregnancy. 2 to 3 weeks of smooth gravidity, following ovariectomy, were ensured on the 6th or 14th day after KB1 by daily application of very low doses of progesterone only (80 mg) or in combination with estrogens, the ratio being 480:1. PMID- 2241474 TI - Biochemical effect of steroid anaesthesia on some liver function tests in goat. AB - Saffan, as a type of steroid anaesthetic, was tested to demonstrate the effect of its administration on liver function in goat. For this purpose, 40 healthy animals were divided into 4 equal groups. The 1st 2 groups were given 2 or 4 mg saffan/kg body weight (B.W.), respectively. A mixture of saffan (1 mg) and xylazine (0.1 mg)/kg B.W. was given to the 3rd group. Xylazine alone was offered to the 4th group in a concentration of 0.1 mg/kg B.W. Serum samples from all groups were analysed to measure the quantities of glucose, total protein, total and direct bilirubin as well as the activity levels of transaminases. Increased glucose levels resulted from administration of saffan which evoked more hyperglycaemia than its mixture with xylazine or xylazine alone. The hyperglycaemic effect of both doses of saffan was equivocal beyond 2 hours. The effect then differed, and glucose elevation reached the 4 fold level by 2 mg saffan and the 3 fold level by 4 mg. Total serum protein, direct and total bilirubin as well as GPT and GOT were not changed in the 4 experimental groups. This was a good indication to normal liver function in the course of administration of steroid anaesthetics to goat. PMID- 2241475 TI - [The content of Hb and the hematocrit value in blood and the total proteins, urea, glucose, free fatty acids, Na, K, Ca, Mg, Pa, Fe, Fe-binding capacity, Cu and Zn in the blood plasma of Warmblood horses during feeding with oat-hay or barley-hay rations over a period of 9 months]. AB - 4 horses (Group A) received an oat-hay ration, through 9 months running, while 3 horses (Group B) were fed a barley-hay ration over the same period of time. Blood samples were collected and examined in 4-week intervals. All values considered, no differences were found to exist between the 2 groups with regard to Hb and haematocrit in blood as well as to protein, glucose, sodium, potassium, magnesium, iron fixation capacity, copper, and zinc in blood plasma. The urea level in plasma of Group A was higher than that in Group B, values being 5.76 +/- 0.64 mmol/l and 5.14 +/- 0.72 mmol/l. The same applied to free fatty acids, values being 150 +/- 83 mumols/l in Group A and 95 +/- 42 mumols/l in Group B. Calcium was 3.10 +/- 0.27 mmol/l in Group A and 2.92 +/- 0.26 mmol/l in Group B, while the A-B difference in inorganic phosphorus amounted to 1.62 +/- 0.65 against 1.99 +/- 0.77 mmol/l. Group A was inferior to Group B also with regard to iron in plasma, values being 28.6 +/- 2.42 mumols/l against 32.8 +/- 4.62 mumol/l. Causes underlying these differences are discussed in some detail. PMID- 2241476 TI - Study into wild Egyptian plants of potential medicinal activity. Ninth communication: hypoglycaemic activity of some selected plants in normal fasting and alloxanised rats. AB - 31 desert plants belonging to 17 families were collected from different Egyptian localities. 21 plants extracts were orally given to normal rats, and 15 were tested on fasted and to alloxanised rats. The results were compared with a standard oral hypoglycaemic drug (Daonil, Hoechst) used as a positive control. The following findings were obtained: 8 plants exhibited persistent hypoglycaemic effects, Lycium shawii, Salvia (S.) aegyptiaca, Pergularia tomentosa, Convolvulus (C.) althaeoides, Haloxylon salicornicum, Ephedra alata, Scrophularia deserti, and Crotalaria aegyptiaca. Transient hypoglycaemic effects appeared only 1 hour after administration in response to 4 plants, Silena succulenta, Lygos raetam, C. lanatus, and Pulicaria incisa. In the cases of Ochradenus baccatus and Zygophyllum album, slow hypoglycaemic activity was produced and appeared 3 hours after administration. 5 plants showed hypoglycaemic effects viz, Thymus capitatus, Launaea nudicaulis, Conyza dioscorides, Nitraria retusa, and Limonium tubiflorum. Among the 15 plant extracts tested on alloxanised diabetic rats only 4 showed hypoglycaemic effects more potent than those of the administered dose of Daonil. These were Matthiola livida, S. aegyptiaca, Astragalus species, and Arthrocnemum glaucum. The hypoglycaemic effect of S. aegyptiaca in fasting rats has been confirmed also in alloxanised diabetic animals. This emphasises the importance of conducting both experiments in order to obtain a reliable conclusion. PMID- 2241477 TI - [Clinical study results of the embryonic development in gilts and brooding performance of gilts and sows after HCG treatment on the 11th day of pregnancy]. AB - Forty-four pregnant gilts were slaughtered on the 32nd and 33rd days of pregnancy, after 30 of them had received 100 or 400 IU of HCG on the eleventh day of pregnancy. Both doses had resulted in higher number of living embryos. Embryo survival rates of treated sows were up to 14.9 percent higher than those of untreated animals. Higher numbers of embryos had no adverse effect on their mass development. Fertility was measured of 77 HCG-treated and untreated gilts as well as of 54 adult sows. The number of non-pregnant sows which returned to oestrus was higher in the group of gilts and adult sows which had received treatment. The number of pregnant animals in the treated adult sow group was seven percent higher than that in the control group. Increased litter sizes were additionally recordable from those gilts and adult sows that had received HCG injections. Yet, those higher litter sizes were associated with lower weight of live-born piglets. In further studies more attention should be given to possible stimulation of LH secretion in early gravidity. PMID- 2241478 TI - [The content of Hb in blood and the protein, Fe, Fe-binding capacity, Cu and Zn in blood plasma of low parity sows before and after oral iron administration]. AB - In investigations of 51 pregnant sows, blood Hb levels above 7.45 mmol/l (mean value of 8.94 +/- 0.88) were recorded from 43 animals (Group A), while levels below that margin were recorded from eight (Group B) (mean value of 6.73 +/- 0.31). Iron levels in blood plasma of Group A were 36.9 +/- 8.07 and were thus higher (p less than 0.01) than those in Group B (28.9 +/- 5.19 mumol/l). No difference was found to exist between the two groups with regard to iron fixation capacity as well as copper and zinc in blood plasma. Oral uptake of 50, 500 or 2,000 mg of iron in the form of FeSO4.7H2O with cereal shred as morning ration by 17 or 15 sows failed to cause any increase in blood plasma iron levels, within 360 minutes from uptake. Literature data as well as the results of these analyses have supported the recommendation that Hb variations between 4.96 and 9.93 mmol/l (8-16 g/dl) should be rated as physiological in the blood of pregnant sows. The GDR Standard TGL 35,423 on "Monitoring of Metabolism on Pig Breeding and Fattening Units" should be accordingly amended. PMID- 2241479 TI - [The effect of intravenous administration of arginine and glycine on the blood plasma content of glucose, insulin, free fatty acids and total alpha-amino-N compounds in lambs of different ages]. AB - Intravenous infusion of 0.5 mmol/kg B.W. to lambs aged eight to 14, 15 to 21, 22 to 28, and 29 to 35 days led to higher blood plasma levels of insulin and total alpha-amino-N. Rises were stronger and longer lasting after infusion of 1.25 mmol/kg B.W. of arginine. Blood plasma levels of glucose and free fatty acids were temporarily decreased in response to infusion. Infusion to lambs aged between eight and 14 days of 0.5 mmol/kg B.W. of glycin did not change insulin, glucose nor free fatty acids, though total alpha-amino-N was very slightly increased for very short time. Infusion of 1.25 mmol/kg B.W. of glycin proved less effective than that of arginine with regard to higher levels of insulin and total alpha-amino-N. PMID- 2241480 TI - Use of dexamethasone for induction of parturition in goats. AB - Parturition was induced in 5 goats of Beetal and Beetal x Black Bengal cross in advanced stages of pregnancy, using intramuscular injection of 10 mg of dexamethasone. Goats required 47.7 +/- 1.26 hours on average after injection for parturition. There were no deleterious effects of induction on placental expulsion, kid weight, kid survival, and postpartum fertility of does. Plasma concentrations of progesterone and oestradiol 17 beta followed a similar trend in controls and treated animals. While plasma progesterone concentrations declined before parturition, the oestradiol concentration rose to its peak on the day of parturition. PMID- 2241481 TI - Pharmacokinetics and renal clearance of ampicillin in sheep. AB - Pharmacokinetics and renal clearance of ampicillin were investigated in 13 sheep, following one single oral dose of 750 mg. A peak concentration in plasma 0.38 +/- 0.04 microgram/ml (mean +/- SEM) was achieved 95.3 +/- 5.95 min after drug administration. Absorption half-life was 44.4 +/- 4.4 min. The area under the plasma concentration curve was 94.6 +/- 4.5 micrograms.hour.ml-1, while in the case of urine it was 370.5 +/- 28.3 micrograms.hour.ml-1. Biological half-life of ampicillin was 110 +/- 3 min, with an elimination rate constant of 0.0064 +/- 0.0002 min-1. The values for volume of distribution and total body clearance were 8.2 +/- 0.71/kg or 52.0 +/- 4.2 ml/kg/min, respectively. The priming and maintenance doses, using MIC as 0.05 microgram/ml, were suggested to be 8.8 or 8.4 mg/kg, respectively, at an 8-h interval. For MIC of 0.5 microgram/ml, this dose should be 10 times higher. Renal clearance of ampicillin seemed to involve active tubular secretion. Renal excretion indicated either extensive metabolism or excretion through routes other than kidneys. PMID- 2241482 TI - Evidence of identification of peste des petits ruminants from goats in Egypt. AB - Peste des petits ruminants virus was isolated from young goats in an outbreak of the disease for the first time in Egypt. Affected goats showed symptoms simulating rinderpest, disease in cattle. The mortality rate was about 30%, and morbidity reached 90%. History, clinical symptoms, postmortem lesions, and diagnosis were discussed. PMID- 2241483 TI - [The colonization of the upper respiratory tract and the bacteremic phases of enzootic pneumonia of calves]. AB - Twenty calves, following their re-accommodation on a calf raising unit, were tested twelve days for presence of Pasteurellae and mycoplasms on the mucosa of the nasal pharynx and in blood. The same microorganisms were searched for in another 65 calves, yet, only at the beginning of pneumonia. Tests were applied to 19 calves for presence of chlamydia in the blood. The nasopharynx of all 20 calves was colonised by Pasteurellae, whereas mycoplasms were detected only in few cases. Neither Pasteurellae nor mycoplasms were isolated by blood culturing, though chlamydia were found in concomitance with pneumonia in three of 13 evaluable cases. PMID- 2241484 TI - [The use of 60Co-gamma ray-sterilized calf serum in cell culture]. AB - The use of 60Co-gamma-radiation-sterilised calf sera in cell culturing is reported in this paper. Evidence was produced to the effect that 60Co-gamma irradiation, using a dosage of 3 kGy and a dose rate of 8 kGy/h, of fetal calf serum, neonatal calf serum, and calf serum did not substantially alter the growth stimulating properties of those sera during 42-day tests. With almost all cell lines and sera used, for all practical purposes, they were identical with the properties of control sera. The following cell lines were used in the experimental programme: one human mammary tumor, MaTu, one human embryonic cell line--E VI, one bat lung cell line--Tb1-Lu, and one human rhabdomyosarcoma--A 204. Growth stimulation was twelve percent below the control value only with Tb1 Lu on Eagle-MEM culturing medium with 3-kGy-irradiation of neonatal calf serum. On the other hand, cell growth was stimulated by 28 percent in A 204 on RPMI 1640 culturing medium, again with 3-kGy-irradiation of neonatal calf serum. Loss of activity by up to 30 percent, depending on the serum used, must be expected from irradiation doses of 10 kGy and 20 kGy which are capable of causing drastic reduction or even complete elimination of serum-borne microorganisms (Bender et al., 1989). Sera irradiated that way would be only conditionally applicable, when it comes to highly vulnerable cell strains. PMID- 2241485 TI - Pregnancy diagnosis by milk progesterone on days 18, 22, and 24 postbreeding in dairy cows. AB - Milk samples were collected from 91 dairy cows on days 18, 22, and 24 postbreeding. The progesterone values of these samples were assayed, using enzyme immuno-assay for pregnancy diagnosis. These animals were classified by nonpregnant (low progesterone values, 5 ng/ml or less) and pregnant (high progesterone values, more than 5 ng/ml). The accuracy of diagnosis on days 18, 22, and 24 postbreeding were 56%, 78%, and 79% for pregnant cows and 90%, 93%, and 93% for nonpregnant animals. The sampling date had a significant effect on diagnostic accuracy (P less than 0.05). PMID- 2241487 TI - [The pathomorphology and pathogenesis of acute cardiovascular failure in swine. 1. Histopathologic findings in the myocardium of swine of different age groups]. AB - Myocardia were histologically examined for the presence of pathomorphological processes in 143 pigs of varying age groups (one, three, seven to nine, and 24 months). Some of them had been slaughtered in clinically intact condition. Others had died of non-cardial diseases. Numerous alterations were recorded, with the following among them being more suitable than others for quantitative assessment and thus objective appraisal of the myocardium: inflammatory infiltrations, granular or hyaline disintegration of fibres, fibre necrosis, dystrophic calcification of fibres, degenerative fat infiltration, and sarcosporidiosis. These parameters were increasingly detectable along with growing age of animals. Inflammatory infiltrations were among the most common findings from pigs for slaughter, aged seven to nine months (40.4 percent of myocardial samples or 58 percent of hearts), followed by muscle fibre necroses (26.4 or 42.0 percent). Most of these disorders were but slightly manifest and were considered to be indicators of catabolic or reparative processes in the myocardium. Attention should be given to them, whenever it comes to pigs with cardiac or circulatory disturbances. PMID- 2241486 TI - [The effect of long term bentonite administration on mixed element metabolism in dwarf goats]. AB - Pigmy goats were experimentally examined for the effects of subchronic oral applications of high doses of GDR-made bentonite on their mass element status (calcium, phosphorus, magnesium sodium, potassium). The argillaceous mineral caused slightly reduced incorporation of calcium in the bones. Bentonite-related reduction of alkaline phosphatase activity cannot be ruled out as a causative factor. Magnesium concentrations in blood serum and liver of bentonite-treated pigm goats were lower with significance than those recorded from controls. Phosphorus, sodium, and potassium metabolism was not substantively altered by bentonite application. A sodium substitution effect might possibly be achieved by admixture of bentonite to feed rations. PMID- 2241488 TI - [The pathomorphology and pathogenesis of acute cardiovascular failure in swine. 2. Histopathologic findings in the myocardium of swine of different populations]. AB - Histopathological alterations of the myocardium (inflammatory processes, fibrolysis, fibronecrosis, dystrophic calcification, fatty degeneration of fibres, sarcosporidia) were recorded for quantitative evaluation from 200 hearts which had been collected from clinically intact pigs for slaughter of different populations (Leicoma, land race, Schwerfurt breed, Belgian land race). Both incidence and severity of myocardial damage in pigs of stress-sensitive populations were higher with significance than those in the less stress-sensitive Leicoma population oriented to breeding. The highest rate of pathological processes was recorded from hearts of the Schwerfurt breed. These alterations were interpreted as objectively measurable expressions of breed-dependent differences in cardiovascular stability. In this context, rates of damage were higher in hearts of low absolute mass. PMID- 2241489 TI - [The pathomorphology and pathogenesis of acute cardiovascular failure in swine. 3. Histopathologic findings in the myocardium of swine with transport-related cardiovascular insufficiency]. AB - Quantitative pathohistological investigations were performed on 300 samples of five different myocardial regions from 50 pigs with had suffered stress-related myocardial insufficiency on their transport to the slaughterhouse (transport exhaustion). The findings were compared to 1,200 myocardial samples from 200 clinically intact pigs for slaughter. Animals with transport-related damage exhibited with significance more and more severe inflammatory and degenerative myocardial alterations, such as round-cell infiltration, fiber necrosis, calcification, and fat infiltration. Many of these lesions had been manifest already prior to transport. Myocardially predamaged pigs were less capable than others of sustaining transport stress and were more predisposed to cardiac failure. Stress-related cardiovascular insufficiency, consequently, depended not only on direct stress but also on the general health condition of the myocardium. Causes and pathogenetic relevance of these alterations are discussed in some detail. PMID- 2241490 TI - [Respiration and motility of epididymal sperm from slaughtered bulls]. AB - The simple method of retrograde flushing of spermatozoa from the epididymal cauda of slaughter bulls yielded an average of 2 x 10(9) spermatozoa from one cauda. The plasma membrane was intact in something between 80 and 85 percent of all epididymal spermatozoa. Respiratory rates and motility were clearly below values typical of ejaculated spermatozoa, though sizeable differences were found to exist for both parameters between individual preparations. The endogenous substrates available proved to be sufficient for such low metabolic activity, whereas higher energy turnover required the presence of exogenous substrates, such as lactate, pyruvate or fructose. Respiratory capacity, determined by uncoupling of oxidative phosphorylation in the presence of lactate, was comparable to that of ejaculated bull spermatozoa. The above findings are likely to suggest that the lower respiratory rates of epididymal spermatozoa were attributable to the fact that their consumption for motility of adenosine triphosphoric acid (ATP) was lower than that of ejaculated spermatozoa. PMID- 2241491 TI - Adaptability of buffaloes to climatic stress, as assessed by physiological reactions. AB - Among the physiological reactions to climate, the haematocrit value had a tendency to increase in the hotter months, though the increase observed was within physiological limits. Rectal temperature did not change to significantly higher levels, during the months with average ambient temperatures in the region of 25.1-31.6 degrees C. Similarly, pulse rates, too, increased in parallel to rising ambient temperatures. PMID- 2241492 TI - [Haemophilus somnus--properties and isolation]. AB - An account is given in this paper of characteristic parameters of Haemophilus somnus, the aetiological factor of various cattle diseases. Morphological properties of the pathogen are described together with techniques for isolation and identification. Also discussed are its physiological, biochemical, and antigenic properties as well as its present position in taxonomy and the structure of the outer membrane. PMID- 2241493 TI - [The biomorphosis of the kidney in swine. 2. Kidney cortex and kidney medulla]. AB - Information recorded from structural development of kidney in swine foetuses of different age and in piglets together with functional data has shown that, notwithstanding progressing maturation, the capacity of renal corpuscles and tubules in piglets was less developed than in other species. Milk deficit or insufficient drinking water or medication may be considerable burdens on the kidney of newborn piglets and may cause stress-related damage. PMID- 2241494 TI - Biochemical studies into variation and repeatability of glutathione concentrations in bovine and bubaline semens. AB - Repeatability (r) value of glutathione (GSH) content was estimated in semen of Tharparkar, Red Dane, their crosses, and Murrah buffalo bulls. Mean GSH values were higher in bovine bull semen as compared to mean GSH values in bubaline bull semen. The r of GSH concentration for the pooled data was 0.1278. This trait is 12.78% repeatable. GSH value in semen of bovine and bubaline bull differed insignificantly. R estimates are expressed for selection of bulls of higher fertility and semen quality. PMID- 2241495 TI - Thermoregulatory effects and electrical conductivity in vagina of cow during oestrous cycle. AB - Measurement of vaginal temperature and electrical conductivity of cervicovaginal mucus were conducted in 20 dairy cows and were related to the phase of the oestrus cycle. Temperature and electrical conductivity in the anterior part of the vagina changed in synchronicity with phases of the oestrous cycle. About 12 hours before ovulation, the vaginal temperature increased from 37.94 +/- 0.33 degrees C to 39.00 +/- 0.64 degrees C, as compared to the pre-oestrus value. The occurrence of oestrus was accompanied by an increase in electrical conductivity of mucus in the anterior part of the vagina from 7.60 +/- 0.33 mS to 12.00 +/- 0.54 mS. Vaginal temperature dropped to 38.50 +/- 0.29 degrees C, and electrical conductivity dropped to 10.00 +/- 0.55 mS at ovulation time. Rises in vaginal temperature and electrical conductivity in the anterior part of the vagina were additional symptoms of oestrus and were followed by decrease in these values, indicating ovulation in cows. PMID- 2241496 TI - Prenatal development of adenohypophyseal cell types, ovary, and uterus of dromedary camel. AB - The somatotrophic and thyrotrophic cells were originally developed in the adenohypophysis from undifferentiated chromophobic cells at the foetal age of 4-8 weeks. The follicle-stimulating hormone cells appeared at a foetal age of 24-28 weeks. Prolactin and luteinizing hormone cells were first seen at of foetal age levels of 32-36 and 40 weeks. The germinal epithelium of flattened and cuboidal cells in the ovary was changed to cubical and columnar types, 24-28 weeks of foetal age. The sex cords appeared at 8-12 weeks of foetal age. The primary and secondary follicles were observed at 8-12 and 20-24 weeks of foetal age, respectively. Follicular cavity was noticed at 32-36 weeks, while large follicles encapsulated by follicular sheath were seen in the 40th week of foetal age. Some ovarian follicles degenerated during or after their development. Surface epithelium in the uterus changed from cubical to columnar type at 8-12 weeks of foetal age. The endometrium was clearly distinguished from the myometrium at 16 20 weeks of foetal age. The uterine glands appeared at 16-20 weeks as short and straight tubular glands, and they began to branch in the 40th week of foetal age. PMID- 2241497 TI - [The effect of long-term bentonite administration on the metabolism of selected trace elements (Fe, Cu, Zn, Mn) in the dwarf goat]. AB - Experiments were conducted with dwarf goats to investigate effects of 160 days of oral application of high doses of bentonite on the trace element status (Fe, Cu, Zn, Mn). High levels of iron compounds in bentonite batches caused intensified incorporation of these elements into liver and kidney of dwarf goat. Copper and zinc incorporations were reduced but manganese incorporation was increased by oral application of bentonite. PMID- 2241498 TI - [The hormone profile in the blood plasma of heifers after cycle synchronization with prostaglandin F2alpha]. AB - Highly sensitive radio-immuno assay (RIA) was used for 21 days to study the curves of several steroid hormones, progesterone (P), oestradiol 17 beta (E2), and testosterone (T), as well as of luteinizing hormone (LH) in peripheral blood of six heifers to which oestrus had been induced by prostaglandin F2 alpha. The validity of the authors' RIA for P, E2, and T determination in blood plasma was positively verified by two reliability criteria, correctness and accuracy, as well as by comparative determinations, using reference methods. Only four of the six heifers returned to oestrus, within 21 days from first oestrus induction. A typical cycle-related curve of the P concentration in peripheral blood with peak values between the 13th and 17th days of cycle (15-26 nmol/l) was recorded from four animals. The peak values of pre-ovulatory E2 and LH were between 33.0 and 53.2 pmol/l or between 19.5 and 52.5 micrograms/l. Some of the T rises in peripheral blood were in parallel to E2 concentrations. All hormone curves are presented in detail and are discussed in relation to clinico-physiological findings. PMID- 2241499 TI - [Steroid hormone levels in follicular fluid of swine with spontaneous estrus and ovulation synchronization]. AB - The steroid hormones oestradiol 17 beta, oestrone (E1), testosterone (T), and progesterone (P) were quantitatively determined in follicular fluids in the pre oestric phase of pigs with spontaneous oestrus and synchronised ovulation. As a whole, mean steroid hormone concentrations exhibited characteristic curves in spite of a relatively wide scatter of individual values. Drastic decline in oestrogen concentration in pigs with spontaneous oestrus and synchronised ovulation was accompanied by rise of P levels, while T values stayed relatively constant. As compared to spontaneous oestrus, treatment for synchronised ovulation caused significantly higher increases in follicular T levels. Positive (P) or negative (E1, T) correlations were found to exist between follicle size and steroid hormone concentration. Conclusions are suggested for further studies. PMID- 2241500 TI - Influence of general anaesthesia (thiopental sodium) on progesterone and cortisol levels in pregnant goat serum. AB - 6 pregnant Baladi goats underwent general anaesthesia, using thiopental sodium. Intravenous application of 10-15 mg/kg body weight of thiopental sodium in 2.5% solution produced light anaesthesia for about 20 minutes. The effect of general anaesthesia on progesterone and cortisol levels was studied before and during the application of anaesthesia as well as 1/2, 1, 4, and 24 hours after anaesthesia. Progesterone was determined by RIA and cortisol by competitive protein binding reaction. Decrease in progesterone and rise in cortisol were noticed during and after anaesthesia. 4 of 13 foetuses were aborted 1-2 weeks after the application of anaesthesia. 6 were born dead. 2 died few hours after birth, and 1 stayed alive. PMID- 2241501 TI - Sequential changes in plasma progesterone, total oestrogens and corticosteroids in cow throughout pregnancy and around parturition. AB - Blood samples were taken thrice a week for 2 weeks from 33 pregnant cows in 9 groups, 1 month apart. In addition, blood samples were collected twice daily 1 week from 8 cows before parturition. Plasma progesterone and total oestrogens were quantified by validated radioimmunoassays and total corticosteroids by a competitive protein binding technique. During the 1st 3 month of pregnancy, no remarkable changes were observed from the 3 hormones studied. From the 4th month on, concentrations of progesterone and total corticosteroids decreased significantly (P less than 0.05) and remained fairly constant until the 9th month. Values of total oestrogens increased significantly (P less than 0.05) from the 4th to 6th months and stayed unchanged afterwards. Progesterone levels in periparturient cows decreased linearly (P less than 0.01) during 3 days preceding delivery. Concentrations of total oestrogens rose sharply from day -5 and peaked at calving. Values of total corticosteroids increased dramatically on the 6th day and 24 hours before parturition. The results obtained suggest that in contrast to studies cited earlier plasma corticosteroids could play a key role for triggering parturition in cows. PMID- 2241502 TI - Relationships between central and autonomic measures of arousal at age 15 years and criminality at age 24 years. AB - Previous studies have indicated that criminality is in part genetically determined, but it is not clear how this predisposition manifests itself at a biological level. This prospective study tests the hypothesis that a psychophysiological predisposition to criminality partly manifests itself through autonomic and central nervous system underarousal. Psychophysiological measures, taken at the age of 15 years, were related to criminality status that was assessed at the age of 24 years. Criminals had a significantly lower resting heart rate, skin conductance activity, and more slow-frequency electroencephalographic activity than noncriminals. Differences were not mediated by social, demographic, and academic factors. These results constitute the first clear evidence that implicates underarousal in all three response systems (electrodermal, cardiovascular, and cortical) in the development of criminality. Although arousal variables correctly classified 74.7% of all subjects, psychophysiological factors alone cannot fully account for criminal behavior and do not negate the potential role of social variables in predicting criminal behavior. PMID- 2241503 TI - Ventricular enlargement in schizophrenia evaluated with computed tomographic scanning. Effects of gender, age, and stage of illness. AB - We evaluated ventricular-brain ratio with computed tomographic scanning in a sample of 108 DSM-III-diagnosed schizophrenic patients and 75 healthy normal volunteers. Significant differences were noted between the patients and controls, but our large sample size also permitted us to determine that the statistically significant difference was contributed primarily through the male patients. Ventricular enlargement occurs only in some schizophrenic patients. In this particular sample, only 6% of schizophrenics had ventricular-brain ratios greater than 2 SDs from the control mean, and 28% were 1 SD greater than the control mean. However, the corresponding figures for male schizophrenics were 19% and 43%, indicating that there is much less overlap between normal individuals and ill subjects in the male population. First-admission schizophrenic patients also had significantly greater ventricular enlargement than did their age-equivalent normal controls, suggesting that ventricular enlargement in schizophrenia may antedate the onset of symptoms. Examination of ventricular size in schizophrenics and normal subjects from a broad age range suggests that ventricular enlargement does not progress over time at a greater rate in schizophrenic patients than in normal subjects. PMID- 2241504 TI - Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. AB - Using a new and unbiased stereological technique, the total numbers of neuron and glial cells in the mediodorsal thalamic nucleus and the nucleus accumbens were found to be significantly reduced in schizophrenic patients compared with controls. The total neuron and glial cell number in the ventral pallidum and in the basolateral nucleus of amygdala did not differ in the two groups. PMID- 2241505 TI - The hippocampus and parahippocampus in schizophrenia, suicide, and control brains. AB - Recent postmortem studies in schizophrenia have shown abnormalities in medial temporal lobe structures, including the hippocampus and parahippocampus. We tried to replicate previous studies and to explore the specificity of this finding to schizophrenia. The anterior hippocampus and parahippocampal cortex were evaluated for area and shape in postmortem tissue from 12 schizophrenic, 17 nonschizophrenic suicide, and 10 nonpsychiatric control brains. No significant differences were found in hippocampal area, but the parahippocampal cortex was significantly smaller in the schizophrenic group than in the control group. When parahippocampi from right and left sides were analyzed separately, both the suicide and schizophrenic groups had smaller parahippocampi on the right side than did the controls [corrected]. The suicide group exhibited greater parahippocampal areas in the left than in the right tissue samples within the group, while such a difference did not exist in the schizophrenic or control groups. This study demonstrated changes in temporal lobe structures in both schizophrenic and nonschizophrenic suicide groups. PMID- 2241506 TI - Structural brain abnormalities in bipolar affective disorder. Ventricular enlargement and focal signal hyperintensities. AB - Structural brain abnormalities were examined in a sample of 48 patients with bipolar affective disorder who were compared with 54 schizophrenic patients and 47 normal controls. As in our previous work using computed tomographic scanning, lateral ventricular enlargement was due to a diagnostic effect. In this study, the effect was more prominent in the schizophrenic men, while a trend was seen in the bipolar men. Women in both groups did not differ significantly from normal subjects. This finding is possibly consistent with the fact that men have a higher frequency of birth anomalies such as hydrocephalus. Since one cause of such birth anomalies might be periventricular hemorrhage or infarction, we also evaluated all scans for the presence of small focal regions of signal hyperintensity. A significant increase in the number of focal signal hyperintensities was noted in the bipolar patients, in comparison with normal subjects, but not in the schizophrenics. The bipolar patients with focal signal hyperintensities had a trend toward larger ventricular size than those without. The pathophysiological significance of these findings is unclear. PMID- 2241508 TI - Neuropsychological assessment of monozygotic twins discordant for schizophrenia. AB - A comparison of monozygotic twins discordant for schizophrenia controls for genetic variance and reduces variance due to environmental circumstances, thus serving to highlight differences due to phenotypic-related variables. In this study, we assessed 16 such twin pairs on a wide range of neuropsychological tests. The affected twins tended to perform worse than their unaffected counterparts on most of the tests. Deficits were especially severe on tests of vigilance, memory, and concept formation, suggesting that dysfunction is greatest in the frontotemporal cortex. While manifest symptoms were not highly associated with neuropsychological scores, global level of functioning was. To address the issue of genetic liability, we also compared the sample of discordant unaffected twins with a sample of seven pairs of normal monozygotic twins. No significant differences between the groups were found for any neuropsychological test. In fact, the results suggest that neuropsychological dysfunction is a consistent feature of schizophrenia and that it is related primarily to the clinical disease process and not to genetic or nonspecific environmental factors. PMID- 2241507 TI - Structural and functional characteristics of the corpus callosum in schizophrenics, psychiatric controls, and normal controls. A magnetic resonance imaging and neuropsychological evaluation. AB - In 1986 Nasrallah and colleagues found that increased thickness of the corpus callosum may be specific to right-handed female schizophrenics. Male and female right-handed schizophrenics were compared with normal and psychiatric controls of comparable age, sex, education, and social class on measures of callosal thickness from a midsagittal magnetic resonance imaging cut and neuropsychological tests of interhemispheric transfer. The sex difference in anterior and posterior callosal thickness in normal controls was reversed in schizophrenics, with the corpus callosum being thicker in female schizophrenics and thinner in male schizophrenics. Similar findings were also observed in the psychiatric control group. These structural differences were not paralleled by evidence of impaired interhemispheric transfer on neuropsychological tasks. These results support the finding of sex-dependent callosal abnormalities in schizophrenia but indicate that these abnormalities may not be specific to this illness. PMID- 2241509 TI - In vivo DNA adduct formation by benzo(a)pyrene in mouse and rat epidermal and dermal fibroblasts after topical application of an initiating dose of benzo(a)pyrene. AB - In vivo adduct formation by benzo[a]pyrene (BP) has been compared in mouse and rat epidermal keratinocytes and dermal fibroblasts after topical application of an initiating dose of carcinogen. The BP-DNA adducts were analyzed by chromatography and acid hydrolysis of BP-deoxyribonucleoside adducts to BP tetrols. BP was dissolved in acetone and applied, at similar doses per unit area (100 nmol/mouse and 240 nmol/rat), to 50-day-old Swiss mice and 35-day-old Wistar rats. Epidermal and dermal cells were isolated twenty four hours later. Reverse phase HPLC of BP-deoxyribonucleoside adducts demonstrated the presence of three BP-deoxyribonucleosides adducts in mouse epidermal cells and one in mouse dermal cells. An unknown product (0.13 and 0.04 pmol/mg mouse epidermal and dermal cell DNA respectively) eluted before the BP-7,10/8,9-tetrol marker, at same relative position as 9-OH-BP-DNA adduct. The major adduct formed in mouse epidermal keratinocytes and dermal fibroblasts was dGuo modified by (+)-anti-BPDE and accounted for more than 70% of the adducts. Acid hydrolysis of the individual BP DNA adducts was used to identify the BP-DNA adducts formed in mouse epidermal and dermal cells as anti- and syn-BPDE-dGuo. Twenty four hours after topical application of BP, the total levels of modified deoxyribonucleosides and (+)-BPDE dGuo were 3 times greater in mouse epidermal cells than in dermal cells. The ratios of anti-BPDE to syn-BPDE was 17:1 and 12:1 in mouse epidermal and dermal cells DNA, respectively. This work provides the evidence that, at an initiating dose, 3H modified deoxyribonucleosides of rat epidermal keratinocytes and dermal fibroblasts are not detectable. This may be essential for the resistance of rat skin to the carcinogenic action of benzo[a]pyrene. PMID- 2241510 TI - Distribution of cisplatin in tumor-free versus tumor-bearing B6D2F1 mice. AB - In healthy as well as in leukemia P388- or melanoma B16-bearing B6D2F1 mice the platinum concentrations in liver, serum and kidneys were determined after i.v. administration of 10 mg/kg cisplatin. In a tumor stage related to about 40% of the mean survival time (MST) no differences in platinum distribution between tumor-bearing and healthy animals could be observed. In the tumor stage related to about 70% of the MST, elevated platinum levels in serum of both tumor models and in kidneys only in melanoma-bearing but not in leukemia-bearing mice could be found. These results confirm those of other authors that tumor stages less than 50% of the MST exert no marked influence on the distribution pattern of cisplatin in rodents. Moreover, in advanced tumor stages distributional differences of antineoplastic agents may be expected between healthy and tumor-bearing mice as well as between animals bearing different neoplasias. PMID- 2241511 TI - [Intensification of hyperglycemic tumor hyperacidity by hypothermia]. AB - On rats hypothermia of 22 to 20 degrees C and rewarming to normal body temperature leads to an amplification of the hyperglycemic tumor acidification. Mechanism and significance of this effect are discussed. PMID- 2241512 TI - [The relation between smear cytology, tumor differentiation, nuclear surface and cytoplasmic estrogen receptor content in cancer of the uterine body]. AB - Forty-one histologically verified endometrial carcinomas were examined to reveal relationship, if any, between cytoplasmic receptor content and tumour differentiation, cytologic diagnosis and mean nuclear surface area. The latter in itself was found to be a reliable prognostic sign of the estrogen receptor positivity of the tumour. PMID- 2241514 TI - Causes of cancer and cancer prevention. AB - Current understanding of the complex processes of cancer causation through a study of the mechanisms of carcinogenesis have documented that there are several major steps each, with distinct quantitative risk assessment factors. The first series of steps, defined by genotoxicity, deal with the assessment of the type of genotoxic carcinogen and its metabolism, leading to a DNA- and macromolecular reactive species. A second area concerns the rate of cell duplication, important in leading to cell transformation to an early neoplastic state. The third key area explores agents that bear on a further development and growth of the transformed cells, an area that has quite distinct dose-response relationships from the first type. Therefore, modulation of the third area provides excellent means of control. In addition, of course, the optimal means is avoiding exposure to genotoxic carcinogens. PMID- 2241513 TI - [The usefulness of monthly breast self-examination for the early detection of breast cancer]. AB - At present, the influence of BSE on mortality reduction from breast cancer is not yet clear. Within a larger case-control study in 195 cases and 390 controls, BSE practice, factors influencing BSE-frequency and the impact of BSE on tumor size as well as on the number of positive lymph-nodes have been investigated. 44% of women practised BSE monthly. Factors significantly positively correlated with BSE were older age, higher education, prior breast biopsy, participation in cervical cancer screening and regular physical breast examination. In comparison to non users, BSE users had a relative risk for breast cancer more than 3 cm in tumor size of 0.65 (0.35-1.21). The relative risk of BSE-users for breast cancer with more than 3 positive lymph-nodes at the time of diagnosis amounted to 0.62 (0.33 1.18). PMID- 2241515 TI - Organization of cancer care in Great Britain. PMID- 2241516 TI - Ernest A. Codman, MD (1869-1940), the end result idea, and The Product of a Hospital. The challenge of a man ahead of his time and perhaps ours. PMID- 2241517 TI - Ernest A. Codman, MD, the end result idea and The Product of a Hospital. A commentary. PMID- 2241518 TI - The product of a hospital. 1914. PMID- 2241519 TI - The seven pillars of quality. AB - Seven attributes of health care define its quality: (1) efficacy: the ability of care, at its best, to improve health; (2) effectiveness: the degree to which attainable health improvements are realized; (3) efficiency: the ability to obtain the greatest health improvement at the lowest cost; (4) optimality: the most advantageous balancing of costs and benefits; (5) acceptability: conformity to patient preferences regarding accessibility, the patient-practitioner relation, the amenities, the effects of care, and the cost of care; (6) legitimacy: conformity to social preferences concerning all of the above; and (7) equity: fairness in the distribution of care and its effects on health. Consequently, health care professionals must take into account patient preferences as well as social preferences in assessing and assuring quality. When the two sets of preference disagree the physician faces the challenge of reconciling them. PMID- 2241520 TI - Appropriateness of medical care. Findings, strategies. AB - Concerns regarding significant levels of inappropriate medical services--as high as 20% or more--continue to influence discussions regarding medical care quality, utilization, and costs. The basis of these concerns are findings from a series of studies of the appropriateness of use of several medical and surgical services provided in the late 1970s and early 1980s--cardiac pacemaker implants, carotid endarterectomy, coronary artery bypass surgery, coronary angiography, and upper gastrointestinal endoscopy. More recent data from Medicare peer review organizations, however, indicate lower levels of unnecessary hospital admissions and medical services. Despite uncertainties regarding the extent of inappropriate care, additional efforts are required to better define appropriate medical care. A promising effort to meet this need is the development of practice parameters, which include practice guidelines and standards. PMID- 2241521 TI - Practice guidelines and outcomes. Where are we headed? AB - Major forces are at work within the health care system that drive the development of clinical standards or guidelines. This process must be tied in a "feedback loop" system to a more accurate assessment of patient outcomes. There is a major controversy at the foundation of the process that is pitting the opinions from consensus panels of experts against the inability of individual physicians to accurately estimate the outcomes of different options through implicit systems. In many instances, the quality of medical evidence is poor. Many groups within organized medicine are attempting to write guidelines, and at least four major challenges must be confronted before guidelines are widely adopted by clinicians. A new federal agency may provide the necessary resources to focus the debate on guidelines. Guidelines may eventually enhance the quality of medical care. PMID- 2241522 TI - Quality assurance measurements in departments of pathology and laboratory medicine. AB - Previously, characteristics of the quality assurance program in each department of pathology and laboratory medicine were the uniqueness of the monitors selected, the thresholds set for activity, and definitions of good performance. In 1989, members of the College of American Pathologists developed and implemented the first nationwide quality assurance program for pathology and laboratory medicine. This program, Q-Probes, has been expanded for 1990; after completion of planning under way for 1991, indicators will be in place for all steps in the total testing process. More than 1100 institutions had subscribed by the first quarter of 1990. Input forms for measurements of clinical indicators of quality are distributed to participants and, after completion, submitted to a central computer facility where keypunching and data manipulations occur. The interpretation of results is enhanced by peer comparisons of the participant data collected. In many circumstances studied, a large proportion of the data are aggregated at extreme ends of the distribution. Because data distributions are nongaussian for the indicators studied, it is recommended that peer comparisons use the 10% to 90% range and that the central tendency be described as the median. Despite large databases for some indicators that exceed by more than 10- to 100-fold those previously reported, extensive categorization may preclude percentile ranking of participants. Critiques are distributed describing practices and suggestions for improvement. Steady improvement of each participant and of nationwide practice patterns are documented by remeasurements. PMID- 2241523 TI - The process of quality assurance. Quality indicators in clinical pathology. AB - The process of developing and using indicators of quality performance in laboratory medicine presents significant problems for clinical pathologists. Although there have been many proposed indicators, many fail to provide meaningful information. Four types of quality indicators (data reliability, laboratory management, clinical utilization, and pathologist credentialing) are proposed and examples of their use are given. PMID- 2241524 TI - Quality assurance goals in clinical pathology. AB - Certain conditions must be fulfilled to meet quality assurance objectives in clinical pathology. Commitment to goals for improving quality and participation by everyone involved are prerequisites. Quality assurance is driven by information that is used to examine processes so that they can be improved. Inspection alone, however, does not produce quality; quality must be designed into the process to reduce the likelihood of errors and to produce long-lasting improvement. Specifications for meeting quality assurance goals should be determined by the expectations of users of the service. Accomplishments are measured by users' perceptions. Integration of laboratory and clinical information, together with communication links between all components of the health care processes, is critical for success. PMID- 2241525 TI - Managing for total quality in a large laboratory. Some examples. AB - A large laboratory, processing more than 30,000 requisitions every 24 hours, provides a unique opportunity to document the value of selected approaches to managing for total quality. Proficiency test errors are an important subset of this database. They can provide a quality control manager with essential diagnostic information if data are analyzed in a systematic fashion. There is no benefit to performing proficiency tests in duplicate or in handling them in a manner different from patients. In fact, error rates can be higher when proficiency tests are handled in a special manner. Finally, error is decreased when technologists receive real-time feedback on how well the process is performing. PMID- 2241526 TI - Quality assurance indicators in anatomic pathology. AB - Quality assurance indicators in anatomic pathology focus on both technical and cognitive processes that result in a written report. The written report serves as both an intermediate outcome, which, in part, determines patient care outcomes, and a source of information for quality assurance studies. General requirements of a program include procedures that meet Joint Commission on Accreditation of Healthcare Organizations requirements for data gathering, data analysis, action, and effectiveness evaluation; documentation; and personnel standards. Specific indicators in surgical pathology and cytopathology focus on timeliness of reports, diagnostic accuracy, relevance of information in reports to the care of the patient, and proficiency testing. Cytopathology requires some unique indicators because of its dual screening and diagnostic role, including detection of false-negative results and comparison of cytotechnologist and cytopathologist diagnoses. Quality assurance indicators for the autopsy include those for the autopsy pathology as a subdiscipline of pathology as well as those that integrate autopsy information into a program of clinical quality assurance. PMID- 2241527 TI - Quality assurance goals in surgical pathology. AB - The development, implementation, and evaluation of quality assurance programs for surgical pathology present special challenges, largely because of the subjective and consultative nature of the "test result" (the diagnostic report). The primary objective of quality assurance is the generation of an accurate, timely, and clinically relevant diagnostic report based on the interpretation of optimal technical preparations. This article defines the essential elements of a comprehensive quality assurance program for anatomic pathology, reviews the role of accrediting agencies in evaluating quality assurance, and describes the various contributions of professional organizations that may influence the achievement of our quality assurance goals. The major emphasis is on those activities that affect the quality of the "outcome" (completed diagnostic report) in surgical pathology and assess its contribution to patient management. PMID- 2241528 TI - A model for the autopsy-based quality assessment of medical diagnostics. PMID- 2241529 TI - Risk management in pathology and laboratory medicine. AB - An effective risk-management program focuses attention on and minimizes events that ideally should not occur. In the laboratory, risk-management issues can be divided along two major lines: (1) patient-care-related issues and (2) employee related issues (safety). The Joint Commission on Accreditation of Healthcare Organizations, Chicago, Ill, has established formal requirements for risk management programs for hospitals and clinical departments. These requirements include patient-care-related activities and management functions related to the safety-management functions. The concept of a formal risk-management program may be new to pathologists and laboratory professionals; the components of the program are traditional elements of laboratory policies and procedures. Key items identified as building blocks for risk management are these: (1) risk prevention, (2) risk identification, (3) risk assessment, (4) corrective actions, and (5) loss control. Through the systematic implementation of a comprehensive risk management program, laboratories have the opportunity to reduce liability exposure and improve the quality of care and services. PMID- 2241530 TI - Resource allocation and the cost of quality. AB - The costs of producing quality medical care and the proper allocation of resources to assure quality are major contemporary concerns. Minimalists attempt to improve quality and lower costs through the application of the theory, "less is more." Bureaucracies make the same attempt through the denial of payments for "unnecessary" services. Governments and insurers try to "improve quality" by impeding the flow of new technology so that costs will be restricted (presumably allowing society better access to current care modalities). All impose regulations and requirements on medical practice. Each of these approaches is examined individually and substantial problems with their application in actual practice are illustrated. Genuine quality is not a cost or resource allocation problem. Quality is free. PMID- 2241531 TI - Quality assurance. Sisyphean or sibylline? AB - Quality control and quality assurance are inseparable from the practice of anatomic and clinical pathology and are not new to either of these disciplines. Indeed, the laboratory comparison programs of the College of American Pathologists were founded on such principles nearly a half-century ago. The "rediscovery" of these principles has spawned an industry unto itself and in this event pathology is in danger of entangling itself in an expensive, parallel (not integral) process that may be Sisyphean. PMID- 2241532 TI - Synthesis and pharmacological studies of some (1,4)-naphthoquinono[3,2-c]-1H pyrazoles, 2-substituted amino-1,4-naphthoquinones, and related compounds. AB - Series of (1,4)-Naphthoquinono(3,2-c)-1H-pyrazoles and 2-substituted amino-1,4 naphthoquinones have been synthesised and studied for their possible anticancer activity (animal tumours, Walker 256 carcinosarcoma), Influenza RNA transcriptase activity, antibiotic activity (C. neoformans, T. mentagraphytes, M. canis, A. niger, and C. albicans). PMID- 2241533 TI - Antilipidemic agents, III: Synthesis of some heterocyclic derivatives of beta sitosterol. AB - Four novel series of heterocyclic derivatives of beta-sitosterol were prepared by the reaction of 3-beta-sitosterol hemisuccinate with SOCl2 then with thiols, amines or phenols. These series are: 3 beta-[(3-substituted-4(3H)-quinazolinon-2- yl)thiocarbonylproprionyloxy]stigmast-5-ene; 3 beta- ([4-substituted-5-(4 pyridyl)-4H-1,2,4-triazol-3-yl] thiocarbonylpropionyloxy)stigmast-5-ene; 3 beta- [(5-substituted-1,3,4-thiadiazol-2-yl)carbamoylpropionyloxy] stigmast-5-ene and 3 beta-(substituted carbamoyl or oxycarbonylpropionyloxy)stigmast-5-ene. The antilipidemic activity of representative compounds was studied. PMID- 2241534 TI - [Drug analysis with polarographic methods. 33. Electroanalytic studies of a new benzodiazepine: [6(o-chlorophenyl)-2,4-dihydro-2-[(4-methyl-1-piperazinyl) methylene]-8-nitro-1H-imidazol[1,2-a][1,4]benzodiazepine-1-one (WHO) (loprazolam,1)] and content determination its drug forms]. AB - Loprazolam (1) is a tricyclic benzodiazepine containing a new butazadiene moiety, which has not been investigated by polarography up to now. 1 is reduced in three waves at a DME over the whole pH-region. In BRP (pH 2-9) 10 electrons are consumed in this process. The first step is suitable for the determination of 1 in Loprazolam tablets containing 1 or 2 mg. These tablets are on the pharmaceutical market in several European countries. The mechanism of the electrode process will be reported in the communication XXXIV. PMID- 2241535 TI - [Preparation of theophylline-sodium salicylate suppositories and determination of factors influencing the in vitro dissolution of the active agents]. AB - Suppositories of theophylline-sodium salicylate were prepared with 10 different vehicles and also with tensids and softeners. With the dynamic diffusion method the drug dissolution and the in vitro diffusion were measured. It was established that proper choice of the vehicle is very important. The highest relative in vitro availability was measured in the case of glyceride base with low hydroxyl value. The diffusion of the active agent can be described by an exponential function. PMID- 2241536 TI - [Comparative study of the binding or iosarcol, iopamidol, iopromide, and iohexol to human serum albumin]. PMID- 2241537 TI - Assessing suicide risk in stroke patients: review of two cases. AB - Poststroke depression can be accompanied by suicidal ideation, yet reports of suicide among stroke patients are rare. When untreated, depression can become prolonged and severe. Risk factors for suicide include depression, severe insomnia, chronic illness, and organic brain syndrome. Early clinical assessment of suicide risk factors is essential in the rehabilitation setting. Two patients who developed mood disturbances in the acute poststroke period and eventually committed suicide are presented. Neither patient openly expressed suicidal thoughts to staff or family members. Retrospective analysis of medical records was compared to established suicide risk factors reported in the medical literature. Indirect verbal cues and nonverbal behavior patterns indicating potential suicide risk may have been present. Strategies for evaluation and management of suicidal behavior are discussed. These cases emphasize the need for early assessment of suicide risk by the entire rehabilitation team. PMID- 2241538 TI - A new orthosis for central cord syndrome and brachial plexus injuries. AB - Proximal upper extremity weakness may develop secondary to central cord syndrome due to spinal cord injury or brachial plexus injury. Functional deficits, pain, decreased upper extremity arm swing during gait, and shoulder subluxation are common sequelae of these injuries. This report describes a new orthotic design that can be easily fabricated in two to four hours from readily available materials to compensate for these deficits. This orthosis allows for early participation in activities of daily living for patients with greater proximal than distal upper extremity weakness. The orthosis consists of a figure-eight shoulder harness and unilateral or bilateral forearm cuffs of orthoplast connected to the harness by flexible rubber tubing. The length of the tubing is adjustable through clamps connected to the forearm cuff to allow for variable arm positioning. Three patients, aged 14, 64, and 68, two with central cord syndrome and one with injury to the upper portion of the brachial plexus (Erb palsy) are described. Shoulder girdle musculature was less than 2, biceps less than 2, triceps less than 4, and hands less than 5 in all patients. Benefits from use of this orthosis may include improved arm swing and balance during ambulation, reduced shoulder pain and subluxation, and increased independence for tasks such as carrying lightweight objects, lower extremity dressing, bathing, light homemaking, and leisure activities such as gardening. PMID- 2241539 TI - Dilantin toxicity and depression. PMID- 2241540 TI - Six years unto the next century: the changing and constant faces of the academy and physiatry. PMID- 2241541 TI - Quantitative evaluation of sway as an indicator of functional balance in post traumatic brain injury. AB - The test of sway, using different conditions of stance with measurements of the average radial deviation of the center of pressure and its path length of sway per unit of time, has been shown to be a useful clinical tool in determining balance problems in traumatic brain injury (TBI) patients. Normative values were established to determine if an individual patient's sway values fell within the normal range (mean +/- 2SD). The tests have shown good test-retest reliability for TBI patients. In addition, it has been shown that the sensitivity of the test is sufficient to identify changes in patients' performances as their clinical conditions change. It has been demonstrated that the different stance conditions of the battery of tests become progressively more difficult to perform (from comfortable stance, eyes open and eyes closed, through narrow stance, eyes open and eyes closed, to tandem stance with right or left foot forward, eyes open and eyes closed). By using these subtests, it is easy to distinguish between the performances of able-bodied patients and TBI patients with very mild balance problems. The validity of the measure has been documented by correlating the sway performance with clinical functional performance tests. The test performance also correlates with the patient's own assessment of his or her gait difficulties. The limited data available suggest that the test of sway relates difficulties in static balance to the frequency of falls. Finally, subtests permit identification of specific problems in maintaining balance as a basis for therapeutic intervention.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241542 TI - Age effect on prognosis for functional recovery in acute, traumatic central cord syndrome. AB - The purpose of this study was to determine if age is significant in functional recovery in acute, traumatic central cord syndrome (CCS). Recovery of ambulation, ADL status, and bowel and bladder function were evaluated. A retrospective study tested the hypothesis that functional recovery in 51 consecutive CCS patients was better in younger patients than in older patients. Four patients, all more than 50 years, died. Ability to ambulate independently at discharge was compared in 30 patients younger than 50 years with 21 patients 50 years or older. Results showed that 29 of 30 (97%) of the younger patients were ambulatory compared to seven of 17 (41%) of the older patients (p less than .002). The younger patients were also able to achieve independence in self-care and bowel and bladder function in a significantly greater proportion. The prognosis for functional recovery in acute traumatic CCS should consider the patient's age. The prognosis is less optimistic in older patients, but it is considerably more favorable in younger patients than previously reported. PMID- 2241544 TI - Sensory nerve evoked responses in spinal cord injury. AB - Previous studies have documented the presence of fibrillations, positive waves, and decreased motor evoked response amplitudes in spinal cord injury (SCI) subjects. The purpose of this study was to further evaluate sensory nerve status in this population. Twenty-eight subjects with SCI for at least five months and evidence of spasticity were included. Sural sensory and tibial motor evoked response amplitudes were measured. The mean sural sensory amplitude was 8.0 +/- 5.9 microV (normal = 15.0 +/- 5.3 microV). The mean tibial motor amplitude was 5.1 +/- 4.3 mV (normal = 11.7 +/- 3.8 mV). In six subjects with significantly reduced sural sensory amplitudes, more extensive electrodiagnostic testing was performed. These studies showed diffusely decreased lower extremity sensory and motor evoked response amplitudes and diffuse positive waves and fibrillations in no particular distribution. Thus, subjects with SCI may have sensory as well as motor nerve abnormalities. An intact connection between the second order and primary sensory neuron may be necessary for maintenance of axonal integrity of the primary neuron. PMID- 2241543 TI - Electric discharge patterns of ankle muscles during the normal gait cycle. AB - EMG patterns in ankle muscles were examined during normal gait cycles in 147 healthy asymptomatic adults. In all subjects, the tibialis anterior (Ta) showed marked activities around the toe-off and before the heel-strike, and the gastrocnemius lateral head (Gl) showed marked activity during the midstance phase but no activity in the early part of the swing phase. The Ta activity contributed to ground clearance, prevention of foot-drop, and shock absorption at the heel strike. The Gl activity contributed to push-off from the ground and prevention of foot-drop. The Ta activity consisted of double bursts with (15% of subjects) or without (44%) electric silence in the midswing phase, continuous discharge (33%), and triple discharge patterns (8%). The Gl activity consisted of a single-peak (95%) pattern or double-peak (5%) patterns. PMID- 2241545 TI - Posterior femoral cutaneous nerve conduction. AB - The posterior femoral cutaneous nerve is a sensory nerve comprised of fibers originating from the anterior and posterior divisions of the first three sacral segments. It exists the pelvis distal to the piriformis muscle and proceeds distally, superficial to and between the medial and lateral hamstring musculature. The nerve's major cutaneous distribution is the posterior aspect of the thigh and a variable area of the posterior calf. An electrophysiologic technique to assess the peripheral axons of the posterior femoral cutaneous nerve is described. A recording electrode is placed 6cm proximal to the midpopliteal fossa and the nerve is stimulated supramaximally 12cm proximally on a line between the active electrode and the ischial tuberosity. A ground electrode is placed just proximal to the active recording electrode. The lower extremities of 40 individuals with a mean age of 34 years (20 to 78 years) were examined. The mean peak latency of the response is 2.8 (2.3 to 3.4) msec +/- 0.2msec with a mean amplitude of 6.5 (4.1 to 12.0) microV +/- 1.5 microV. This technique may facilitate the proximal evaluation of lower extremity peripheral neuropathies, lesions of the posterior femoral cutaneous nerve, or the assessment of the peripheral nervous system in persons with lower extremity amputations. PMID- 2241546 TI - Myotonic dystrophy: quantification of muscle weakness and myotonia and the effect of amitriptyline and exercise. AB - The purpose of this study was to quantify the degree of muscle weakness and myotonia in 12 patients with myotonic dystrophy (MD), and to quantitatively determine the effects of a four- to six-month therapeutic trial of amitriptyline. Patients had exercised with weights for one or more years. Some had shown initial improvement in muscle strength, but had reached a plateau; others had not improved when the study began. Muscle weakness was quantified by comparing the five-second maximum voluntary contraction (MVC) in newtons (N) per kg (body weight) of 12 patients and 20 healthy subjects. Knee extensor, elbow flexor, and first dorsal interosseous (FDI) muscles were compared. Myotonia was quantified by measuring relaxation times (RTs) at the end of the five-second MVC produced by FDI, as the time taken for the MVC to decrease by 50% and 75% (referred to as 1/2 and 3/4RT). The results were as follows: (1) the mean muscle strength of each of the three muscles of the patients was significantly (p less than .001) reduced compared with healthy subjects; and (2) 1/2 and 3/4RT means of the patients (vs healthy subjects) were significantly prolonged (p less than .01). Eight of the patients participated in a therapeutic trial of amitriptyline. Therapeutic effects were quantified by measuring muscle strength, 1/2 and 3/4RT, and percent change in evoked muscle action potential (MAP) from the FDI muscle after a ten second MVC, to determine change in excitability. Mean muscle strength of FDI improved from .27 to .33N/kg, (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241547 TI - Foot placement angle and arch type: effect on rearfoot motion. AB - The purpose of the study was to describe the relationship between foot placement angle, arch type, and rearfoot motion during running. Twenty women were filmed in the frontal plane at 100 fps. Subjects displaying a variety of foot placement angles were chosen. Before data collection, arch indices were calculated. Each subject ran five trials at a pace of 3.5 m/sec. All subjects wore the same type of shoe. All trials were digitized to determine rearfoot angles throughout foot contact. The following mean values were obtained: total rearfoot was 10.09 degrees, maximum pronation was -9.63 degrees, foot placement angle was 7.58 degrees and arch index (AI) was 0.23 cm2. Non-linear regression was used to predict the relationship between maximum pronation and total rearfoot motion using foot placement angle and AI. Foot placement angle was the best single predictor of total rearfoot motion. When using both foot placement angle and arch type as predictors of total rearfoot motion, r2 was .35. Less abduction was associated with more total rearfoot motion. Arch type exhibited a quadratic relationship with total rearfoot motion. Normal-arched individuals (.21 cm2 less than AI less than .26 cm2) exhibited less total rearfoot motion than high-arched (AI greater than .26 cm2) and flat-arched (AI less than .21 cm2) individuals. For maximum pronation, foot placement angle was the only significant predictor (r2 = .13). Greater foot placement angles (more abduction) were associated with less maximum pronation. PMID- 2241548 TI - Asymptomatic ulnar neuropathy in carpal tunnel syndrome. AB - Quantitative assessment of the vibration threshold of the second and fifth fingertips at 125Hz was performed on 28 affected limbs of 17 patients with carpal tunnel syndrome (CTS) together with a median and ulnar sensory nerve conduction velocity (SNCV) study. Twenty-six limbs of 26 age-matched healthy subjects were used as controls. Both the vibration threshold elevation of the second finger and the delay of median SNCV were significant in CTS patients as compared with controls (p less than .001). Although the ulnar SNCVs of all affected limbs were within the normal range, ten affected limbs (36%) were found to have a concomitant vibration threshold elevation of the fifth finger, and eight of those limbs were found to be exposed to chronic occupational mechanical stimulation at the wrist. These findings appear to support the presence of subclinical traumatic damage to the ulnar nerve at the wrist. In summary, digital vibration measurement can elucidate subclinical ulnar neuropathy in CTS which cannot be detected by SNCV studies. PMID- 2241550 TI - On the supply of physicians. AB - The congressionally created Council of Graduate Medical Education is conducting a study to assess the adequacy of the current and future supply of physicians in six specialties. The study is revising and updating the needs-based method used by the Graduate Medical Education National Advisory Committee and using this method to project the requirements for physicians for the next two decades. Projections on the supply of physicians will be based on the latest data from the federal government's Bureau of Health Profession's health manpower model. Previous physician manpower studies are reviewed to provide a historic perspective and a frame of reference for the variables, data sources, and assumptions being considered by the Council of Graduate Medical Education study. PMID- 2241549 TI - Nobel Laureate: Joseph E. Murray, clinical surgeon, scientist, teacher. PMID- 2241551 TI - Heart transplantation in Jehovah's Witnesses. An initial experience and follow up. AB - More than 25 years of experience performing heart surgery on Jehovah's Witnesses has culminated in successful cardiac transplantation without administering blood products in five patients (mean age, 44.4 +/- 8.3 years) of this faith. The use of blood-conserving methods, iron supplementation, bone marrow-sparing maintenance immunotherapy, and brisk postoperative diuresis has added to the efficacy of cardiac transplantation in these patients. No perioperative deaths occurred, and early follow-up studies have shown that these patients have not been more susceptible to higher graft rejection rates due to the lack of pretransplant blood transfusions. As more Jehovah's Witnesses undergo heart transplantation in the future, comparison with other recipients who allow pretransplant blood transfusions may lead to a better understanding of rejection immunobiology. We conclude that cardiac transplants may be safely offered to Jehovah's Witnesses without fear of a uniformly poor outcome. PMID- 2241552 TI - Ambulatory cholecystectomy without disability. AB - This is a presentation of 200 consecutive outpatient cholecystectomies performed during a 4-year period in a small community hospital. This technique is performed with minor modifications of the usual cholecystectomy procedure so that it could easily be performed by general surgeons throughout the United States. The procedure has resulted in a large reduction in the short- and long-term morbidity associated with cholecystectomy, and in savings of up to one fourth the cost of a routine inpatient cholecystectomy. This procedure allows the general surgeon to treat patients with cholecystectomies in the fashion to which the surgeon is accustomed and still markedly reduce the hospital stay. The morbidity from this procedure seems comparable with laser cholecystectomy. Ambulatory cholecystectomy as described here does not require any special training or equipment. PMID- 2241553 TI - Postoperative complications in patients with disabling psychiatric illnesses or intellectual handicaps. A case-controlled, retrospective analysis. AB - The purpose of this study was to quantitate the operative risk and costs encountered in the surgical treatment of institutionalized patients. Operative complications and duration of hospitalization for 200 institutionalized patients were compared with those in a control group of patients matched for age, sex, and type of operation drawn from the general hospital population. Postoperative complications occurred in 53 (26.5%) of the patients in the study group compared with 15 (7.5%) of the patients in the control group. Elective laparotomy was followed by a complication in 48% of institutionalized patients compared with 11.6% of matched controls. Emergency celiotomy carried a 75% complication rate in the study group. Atelectasis and pneumonia accounted for 50% of the postoperative complications and occurred with greatest frequency following intra-abdominal procedures. The median hospital stay for all institutionalized patients was 3 days more than for matched controls. A strategy for postoperative treatment is presented, with particular emphasis on prevention of pulmonary complications. PMID- 2241554 TI - Needle-localized mammographic lesions. Results and evolving treatment strategy. AB - From January 1981 to December 1987, 932 needle-localization breast biopsies were performed at our institution for mammographically detected abnormalities. We reviewed 531 needle-localization breast biopsy procedures performed during two periods (January 1981 to June 1984, n = 311; and January to August 1987, n = 220) to compare results and treatment patterns, and to determine the prevalence of the missed lesions. Mammographic abnormalities detected on routine screening accounted for a larger proportion of needle-localization breast biopsies in the later series (94 [30%] of 311 vs 94 [43%] of 220). However, the rate at which carcinoma was identified remained constant at 29% as did the percentage of cancers that were invasive (46% vs 51%). Overall, the rate of malignant diagnoses after needle-localization breast biopsy was lowest in asymptomatic women undergoing routine screening mammography (44 [24%] of 188) and significantly higher in women undergoing mammographic follow-up of the contralateral breast after treatment for breast cancer (28 [43%] of 65). There were seven missed lesions in 531 needle-localization breast biopsies, necessitating a second procedure in six and interval mammograms in one. PMID- 2241555 TI - Aerobic and anaerobic bacteriology of wounds and cutaneous abscesses. AB - The aerobic and anaerobic microbiologic characteristics of 584 wounds and 676 skin or soft-tissue abscesses were studied and correlated with the infection site. In wounds, aerobic or facultative bacteria only were present in 223 specimens (38%), anaerobes only in 177 specimens (30%), and mixed flora in 184 specimens (32%). In total there were 1470 isolates, 558 aerobic and 912 anaerobic, an average of 2.5 isolates per wound (1.6 anaerobic and 0.9 aerobic isolates). In abscesses, aerobic or facultative bacteria were recovered in 177 specimens (26%), anaerobes only in 243 specimens (36%), and mixed flora in 256 specimens (38%). In total there were 1702 isolates, 602 aerobic and 1100 anaerobic, an average of 2.5 isolates per abscess. The highest rates of anaerobes in wounds were in the inguinal, buttocks, and trunk areas and in abscesses in the perirectal, external genitalia, neck, and inguinal areas. The predominant aerobic organisms were Staphylococcus aureus (363 isolates), group A streptococci (98 isolates), and Escherichia coli (97 isolates). The predominant anaerobic organisms were Bacteroides species (986 isolates), Peptostreptococcus species (559 isolates), Clostridium species (153 isolates), and Fusobacterium species (109 isolates). The predominance of certain isolates in certain anatomical sites was correlated with their distribution in the normal flora adjacent to the infected site. These data highlight the polymicrobial nature of wounds and cutaneous abscesses. PMID- 2241556 TI - Reinforcement of colonic anastomoses with a laser and dye-enhanced fibrinogen. AB - The incidence of anastomotic leakage in colonic surgery is approximately 10%. We evaluated a technique of laser-fibrinogen reinforcement to strengthen experimental colonic anastomoses. The technique consisted of the topical application of indocyanine green dye-enhanced fibrinogen to the serosal surface of two-layer inverting anastomoses, followed by exposure with an 808-nm diode laser. In the 28 rabbits used for this study, mean bursting pressure at time 0 was 108 +/- 13 mm Hg in the group receiving anastomoses with sutures alone and 173 +/- 20 mm Hg in the group for which the sutured anastomosis was reinforced with laser-fibrinogen. The difference in bursting pressures between the two groups was statistically significant at time 0. However, at 1, 3, 5, and 7 days, the anastomosis became stronger in both groups and the difference in strength was reduced; the sutured group had more exceptionally weak (less than 110 mm Hg) bonds than the group treated by laser. Thus, laser-fibrinogen reinforcement significantly enhances the early strength of sutured colonic anastomoses. This technique may reduce the incidence of leakage during the first postoperative week and the associated complications in a clinical setting. PMID- 2241557 TI - Hepatic vein reconstruction for preserving remnant liver function. AB - Hepatic malignancies often infiltrate to the major hepatic vein. Recently, we performed hepatic resection combined with hepatic vein reconstruction for preserving remnant liver function in three such patients. One patient had a saphenous vein graft. Postoperative liver function of the patients who underwent hepatic vein reconstruction was compared with those of eight patients who underwent hepatic resection of segments VII and VIII. The right hepatic vein in four of them was resected and in the remaining four was preserved by skeletalization using an ultrasonic aspirator. Although four patients with right hepatic vein resection showed severe lowering of liver function after surgery, the postoperative course of patients with preservation or reconstruction of the right hepatic vein maintained good liver function. Liver regeneration of three patients with hepatic vein reconstruction was good on computed tomography. Besides this report, to our knowledge, there is no other report of hepatic vein reconstruction for preserving the remnant liver function. Problems with hepatic resection combined with hepatic vein reconstruction are discussed. We conclude that hepatic vein reconstruction is one of the means for extending indication of the malignant tumor resection of the liver. PMID- 2241558 TI - Evaluation of methods for detecting venous reflux. Perspectives in venous insufficiency. AB - Using 793 limbs with nonobstructive venous reflux, we evaluated a number of techniques used for the assessment of venous reflux. The venous Doppler examination was found to be a reliable screening tool with excellent sensitivity and good specificity. Photoplethysmography was 97% sensitive in patients with ambulatory venous hypertension; however, in milder forms of reflux, it was less sensitive. The major drawback of photoplethysmography was the large number of false-positive results obtained. Ambulatory venous pressure measurement and another pressure-based technique, Valsalva-induced foot venous pressure measurement, defined overlapping but different normal and abnormal limbs. Descending venography, when performed as described by Kistner et al, was found to be a reliable tool to assess reflux with more than a 90% sensitivity. The horizontal technique of performing descending venography and nucleotide descending venographies had unacceptably low sensitivity and were abandoned. Features of venous reflux as outlined by these modern technical tools are described. PMID- 2241559 TI - Does survival depend on the amount of autotransplanted splenic tissue? AB - Susceptibility to Streptococcus pneumoniae infection was studied in 11 groups of rats allocated to sham operation, splenectomy, or splenic autotransplantation of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the removed spleen. Three months later, all rats were exposed intravenously to type 1 Streptococcus pneumoniae (median lethal dose, LD50, for control group). Survivors were killed 13 days after the bacterial challenge. Autopsy showed that more splenic tissue was recovered in rats that received less than 50% splenic tissue compared with those that received 50% or more. More survivors were found among sham-operated rats (47.5%; 95% confidence intervals, 32 to 68) and rats that had 40% splenic tissue implanted (35%; confidence interval, 20 to 54) or those that were found to have regenerated 40% splenic tissue. We conclude that 40% of the spleen should be autotransplanted to protect the rat optimally against infection after splenectomy. PMID- 2241560 TI - Primary malignant peritoneal mesothelioma. A report of seven cases and a review of the literature. AB - Mesothelioma of the peritoneum is a rare malignant neoplasm easily mistaken by both surgeon and pathologist for one of the more common neoplasms of the abdomen. Review of our records from metropolitan-area hospitals for the past 15 years identified seven patients with primary peritoneal mesotheliomas. Their diagnosis, management, and survival is analyzed. We report a case of an extended survivor (7 years) and one of a long-term survivor (15 years), as well as what we believe to be the only case in the literature presenting with a coexistent malignant neoplasm. Prevention of this commonly fatal neoplasm is linked to avoiding occupational exposure to asbestos; long-term survival for a few patients may be achieved with correct identification of the neoplasm and aggressive management. This report includes a review of the literature. PMID- 2241561 TI - Aortic occlusion and vascular isolation allowing avascular hepatic resection. AB - Occlusion of the supraceliac abdominal aorta and hepatic vascular isolation were employed in a series of 15 patients as a definitive method to allow avascular hepatic resection. The series was compared with an earlier group of patients treated conventionally. In the avascular hepatic resection group there was no mortality; hypotension did not occur at the time of hepatic vascular isolation; rapid, accurate excision of the hepatic lesions could be achieved in a bloodless field; resection of midline lesions and those involving the great veins was possible; and "segmentectomies," or resections crossing segmental boundaries, could be performed where previously formal hepatic lobectomies were required. Concomitantly, the greatest amount of uninvolved hepatic parenchyma remained in situ. There was increased ease of operative management, reduced blood loss, and reduced operating time (mean, 2.8 hours). PMID- 2241562 TI - Management of perineal wounds following abdominoperineal resection with inferior gluteal flaps. AB - Our experience treating perineal wounds secondary to abdominoperineal resection, either for inflammatory bowel disease or cancer, is presented. A total of 16 patients were treated either on a delayed basis or at the same time as the abdominoperineal resection. All wounds were closed using the inferior gluteal myocutaneous flap. Fifteen of 16 patients have achieved healing, eight of whom had no complications. Only minor revisions or local wound care were required in the remaining patients, with only one patient failing to heal. Our results compare favorably with previous reports of treatment of this difficult problem. PMID- 2241563 TI - Antibiotic pharmacokinetics in surgery. AB - Pharmacokinetics is the study of variables that affect drug concentrations at the effector site. The descriptive terms peak concentration, elimination half-life, volume of distribution, and bioavailability are commonly used to express pharmacokinetic variability among drugs used in patient care. The pharmacokinetic characteristics of drugs are important for surgeons to understand because they represent differences that may assume clinical significance when selecting antibiotics for preoperative preventive indications. In addition, the changing hemodynamic pattern of the stressed and septic patient may result in changing pharmacokinetic patterns for an antibiotic, which, in turn, may require changes in the dosing regimen during the course of treatment. PMID- 2241564 TI - A history of the bilioenteric anastomosis. AB - The bilioenteric anastomosis has played an integral role in the surgical management of biliary tract disease during the past century. A wide variety of techniques for suturing a portion of the biliary tract to the digestive tract have been described since von Winiwarter's first cholecystoenterostomy. Many types of biliary stents have also been developed, although their exact role remains controversial. Many advances in preoperative and postoperative care have contributed to the low morbidity and mortality of current reconstructive biliary tract surgery. PMID- 2241565 TI - The papillary-cystic neoplasm of the pancreas. An increasingly recognized clinicopathologic entity. AB - The clinical course of the papillary-cystic neoplasm of the pancreas is contrasted with that of the pancreatic ductal adenocarcinoma. The former occurs predominantly in young women, has a low malignant potential, and is highly curable with surgical treatment. Three cases are reported that illustrate the typical clinical features and the indolent nature of the tumor. One case was discovered after blunt abdominal trauma resulted in rupture of the tumor and hemoperitoneum. All cases were treated by pancreatic resection with preservation of the spleen, an important consideration in younger patients. All patients were free of disease at long-term follow-up. Increasing awareness of this tumor has resulted in the reclassification of several tumors and should lead to better recognition by surgeons caring for patients with pancreatic diseases. PMID- 2241566 TI - Extrahepatic biliary obstruction by lymphoma. AB - Extrinsic compression of the common bile duct by enlarged lymph nodes is an unusual cause of obstructive jaundice. We describe two patients with such a manifestation of lymphoma and the use of endoscopic retrograde cholangiopancreatography in distinguishing this rare complication from other causes of jaundice in lymphoma. Patients may have rapid resolution of both symptoms and biochemical abnormalities by nonoperative biliary bypass combined with chemotherapy and/or radiotherapy. Lymphomatous obstruction should be considered a cause of potentially treatable jaundice in patients with known lymphoma; endoscopic retrograde cholangiopancreatography can be valuable as a diagnostic and therapeutic tool. PMID- 2241567 TI - Elective cholecystectomy after biliary lithotripsy: an indication for routine intraoperative cholangiography? PMID- 2241568 TI - Mathematical model for energy and protein balance simulation in broilers. AB - The authors used the empirical equations of mathematical modelling for the energy and protein balance simulation, with the view of calculating the body weight gain in broilers fed various diets. The results found by using the model were compared with the experimental data obtained by several authors. A standard deviation of +/- 1.20% and a mean error of +/- 0.28% and a mean error of +/- 0.28% which proved that the model average was a sufficient estimate of the experimental average were found. Furthermore, using the regression method, a significant correlation of variables was evidentiated. PMID- 2241569 TI - [The effect of increasing additions of low-esterified pectins in the diet on the metabolism of laying hens--tested by pair-feeding studies]. AB - A series of trials was carried out with 32 laying hens in order to study metabolism after addition of low methylated citrus pectin in levels of 2% and 6%. The following results should be pointed out: Addition of pectic substances reduced feed-intake and stimulated water intake. The limited tolerance for pectins resulted in an increasing water-content of the excreta with a rise of the concentration of volatile fatty acids and an alteration of their spectrum. In consequence of supplementation with pectins a considerable loss of body weight could be established, which exceeded the expected effects of reduced energy intake. The egg production was impaired by addition of pectin. In the serum the level of total lipids, cholesterol, triglycerides, phospholipids, furthermore of bile acids diminished. These effects exceeded remarkably those induced solely by reduced feed-intake. The level of volatile fatty acids in the serum was elevated as result of the supplementation with pectic substances. PMID- 2241570 TI - Studies of the effect of supplementing protected methionine (HMM-Ca) to dairy cows on milk yield and fertility. AB - A trial with 90 cows was conducted to examine the effect of supplementing 30 g N hydroxymethyl-DL-methionine-calcium (HMM-Ca) from 14 days pre calving till 100 days in lactation on the performance and some physiological traits. Cows were kept on four energy levels by feeding different amounts of concentrate. At each energy level, half of the cows were given a methionine supplement. Forage consisted of 1/3 corn- and/or beet pulp silage and 2/3 grass silage ad libitum. The amount of daily milk yield differed not significantly from 31.5 kg for the supplement group to 30.6 kg for the control group. No interaction between the methionine supplementation and energy level could be detected. Mean methionine content in blood plasma differed from 22.7 mmol/l for the supplement group to 16.8 mmol/l for the control group. GOT, tau-GT, bilirubin and urea in blood serum and milk urea content did not indicate a positive effect of the methionine supplementation on the metabolism. Conception rate differed slightly from 87% in the supplement group to 73% in the control group. PMID- 2241571 TI - Effect of low level of dietary aflatoxins on baladi rabbits. AB - Aflatoxins B1, B2, G1 & G2 were administered in a low concentration (100 ppb of each aflatoxin (AN] in a mash offered to Baladi rabbits. An other group of rabbits were fed on the same contaminated mash in addition to 0.25% charcoal (CC). The two groups were compared to control animals fed on AN-free mash. Inclusion of AN in the diet decreased feed and water consumption, body weight and survival rate. Charcoal improved somewhat feed and water consumption and growth rate than AN-group. However, CC-group affected digestibility of organic matter more than AN-group. Relative weights of liver, kidneys, heart and adrenal glands were significantly higher in AN and CC groups than the control group. Blood haemoglobin content, packed cell volume percentage and sedimentation rate were lower in AN group. Although there were an increase in each of serum, calcium, inorganic phosphorus, cholesterol, phospholipids and glutamic-pyruvic transaminase in AN group, yet the serum nitrogen and glutamic-oxalacetic transaminase were reduced. Charcoal had alleviated AN-effects concerning N, GPT and phospholipids. Chemical analysis revealed elevation of water, ash and silica contents of liver and water content of muscles from AN-animals. On the other hand, fat content, GOT and vitamin A in the liver as well as muscles ash were reduced. Addition of CC to the diet reduced AN-effects on liver fat, ash and silica but resulted in a rise of the water content of liver and muscles and liver GPT activity. Charcoal also resulted in a sharp decrease in vitamin A content of the liver. Aflatoxin treatments (in AN and CC groups) reduced bone ash, silica and magnesium as well as bone volume. Charcoal administration increased Ca content of bones. Aflatoxin feeding (in AN group) resulted in a high residual percentage of AN in muscles, serum, liver, heart and kidneys with relationships of 51 :24 : 3 :2 : 1, respectively. Only 1.42% of the fed AN was excreted in the faeces. Charcoal usage had a good effect as it prevented AN to accumulate in the organs. Aflatoxin contaminated diets (in AN and CC groups) resulted in paralysis, disorder of fat deposition, discolouration and haemorrhages of some organs. Scanning electron microscopic examination revealed no ill effect on the surface structure of the small intestine due to either AN or AN + CC. Pathological examination showed that the main affected organs were liver, heart and spleen, respectively. The changes include hepatic round cell infiltration, irregularities of lobular plats, focal necrosis and periportal fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2241572 TI - Transcription of feline calicivirus RNA. AB - We report here the cloning and 3' sequence determination of feline calicivirus strain F9. Subcloning the 3' terminus enabled the production of strand specific probes for RNA synthesis. We extend the number of virus specific RNAs detected intracellularly to 8, and show that numbers 1-5 are represented as negative strands which may serve as templates in the synthesis of these RNAs. PMID- 2241573 TI - Modified oligopeptides designed to interact with the HIV-1 proteinase inhibit viral replication. AB - The human immunodeficiency virus 1 (HIV-1) codes for a proteinase that cuts viral proteins at specific sites. We have tested 13 modified oligopeptides related to these cleavage sites to see if they inhibit viral replication. To indicate whether a decrease in replication could be due to a general inhibition of cell metabolism, we also measured the effect of the peptides on cellular protein synthesis. Three of the peptides tested (Ac-Gln-Asn-Sta-Val-NH2, Ac-Gln-Asn-Sta Val-Val-NH2, and Ac-Glu-Asn-Sta-Ile-NH2) inhibited HIV-1 replication at concentrations that did not inhibit protein synthesis. Ac-Gln-Asn-Sta-Val-NH2 was the most potent, causing an approximately 40% decrease in viral replication, measured as the synthesis of HIV-1 antigens and the formation of infectious particles. PMID- 2241574 TI - Mutational analysis of enhancer domains responsive to trans-activation by the X gene of human hepatitis B virus. AB - The X gene product of human hepatitis B virus (HBV) trans-activates the HBV enhancer. In order to identify domains responsive to trans-activation by the X gene, we introduced a series of mutations into the HBV enhancer and assayed the enhancer activities in the presence of the X gene product. Our results suggest that the EP domain of the enhancer is essential for trans-activation by the X gene. PMID- 2241575 TI - A diagnostic method to detect alcelaphine herpesvirus-1 of malignant catarrhal fever using the polymerase chain reaction. AB - A sensitive diagnostic method specific for alcelaphine herpesvirus-1, causative agent of malignant catarrhal fever, has been developed. Based on the nucleotide sequence of the alcelaphine herpesvirus-1 genomic DNA, a pair of 30 nucleotide primers was selected and synthesized for detecting the virus genome using the polymerase chain reaction (PCR). The virus genome was detected in crude cell lysate using the amplification reaction. PMID- 2241576 TI - Sequence homology between HIV gp120, rabies virus glycoprotein, and snake venom neurotoxins. Is the nicotinic acetylcholine receptor an HIV receptor? PMID- 2241577 TI - Comparison of the genomes of two sympatric iridescent viruses (types 9 and 16). AB - A map of the sites in the genome of Costelytra zealandica iridescent virus (CzIV), using the restriction enzymes BamHI, KpnI, and PstI, showed the genome size to be 170.2 kbp in length. It was found that the genome was cyclically permuted and that 39% of the genome of CzIV contained repetitive sequence elements. The genome was found to hybridize with the genome of another iridescent virus, type 9 (WIV), in DNA-DNA hybridization experiments. A region of the WIV DNA genome (23.4 kbp) did not hybridize with CzIV DNA and this region is similar in size to the total genomic size difference between CzIV and WIV (22.4 kbp). A unique repeat sequence from iridescent virus type 6 (CIV) was shown to be present in the genome of WIV but not that of CzIV. Finally, the positions of the major capsid protein genes, VP53 and VP52, in the restriction enzyme maps for type 16 and type 9 respectively were determined. PMID- 2241578 TI - Electron microscopy, plaque assay and preliminary serological characterization of three ectromelia virus strains isolated in Poland in the period 1986-1988. AB - Three strains of viruses have been identified as ectromedia virus (EV) based on their origin, clinical features, morphology, size of virions (140 x 220 nm), replicative ability and specific cytoplasmatic fluorescence. The mean diameter of plaques produced by EV strains was 0.76 mm (range 0.5-1.0 mm). The neutralizing properties of the tested sera were evaluated by seroneutralization (SN) and hemagglutination inhibition (HAI) tests. PMID- 2241580 TI - [The treatment of chronic asthma and its long-term results]. PMID- 2241579 TI - Cytotropism of Theiler's murine encephalomyelitis viruses in oligodendrocyte enriched cultures. AB - The cytotropism of two strains, GDVII and DA, of Theiler's murine encephalomyelitis viruses (TMEV) was studied in the oligodendrocyte-enriched murine neural cell cultures. Both GDVII and DA caused cytopathic effects in the neural cell cultures, and double immunostaining for galactocerebroside (Gal-Cer), a marker molecule for oligodendrocyte, and viral antigens disclosed a dual expression of Gal-Cer and viral antigens in over 80% of cells in both cultures 24 h after infection with either GDVII or DA. The kinetics of cell-free and cell associated infectivity were not significantly different between two cultures. These in vitro observations suggest that neither replication in oligodendrocyte nor cell-associated infectivity is a sole factor in discriminating those two subgroups of TMEV with regard to the demyelinating activity, and that virus cell binding may play an important role in virus persistence and TMEV-induced demyelination. PMID- 2241581 TI - [Evaluation of venom specific IgE and total serum IgE among forest administration workers]. AB - We used a questionnaire to investigate Hymenoptera hypersensitivity in 323 forest administration workers and measured total serum IgE and venom specific IgE antibodies against yellow jackets and paper wasps. The results were as follows. 1) Most of the workers, including 69 (21.8%) hypersensitive workers, had been exposed to stings by yellow jackets or wasps. 2) The titer of RAST (p less than 0.05) and RAST positive rate (p less than 0.01) were higher in the hypersensitive workers than in the non-hypersensitive ones. 3) There was a correlation between venom specific IgE titers to yellow jackets and paper wasps (rs = 0.818). 4) The titer of venom specific IgE increases with the frequency of sting exposure, and decreased gradually with the passage of time. 5) The higher the venom specific IgE titer, the higher the total serum IgE titer. 6) The titer of venom specific IgE, total serum IgE and atopy had no relation to the severity of clinical symptoms. PMID- 2241582 TI - [Long-term follow up studies of bronchial asthma in children. II. Prognosis and complications, treatment and allergic evaluations]. AB - A questionnaire on the prognosis of bronchial asthma was sent in 1988 to 1592 patients (1038 males, 554 females) averaging 20 years of age after 12 years' follow up. We reported on the prognosis and risk factors associated with asthmatic children in part I. The relation between prognosis and other allergic complications, treatment and laboratory data were investigated in this study. Eosinophil counts of more than 1000/mm3 and/or total serum IgE levels of more than 500 IU/ml (100 IU/ml in infants) indicated poor prognosis. However, the prognosis was not affected either by the allergens themselves or by the number of allergens determined by skin test and RAST. The prognosis was worse for patients with multiple allergic complications than for those without complications. Treatment may after the natural course of childhood asthma, but it has been difficult to evaluate the effect of each regimen over a long period. We compared the effect of hyposensitization (specific immunization) and non-bronchodilator antiasthmatic drugs (NBAAD), and found that hyposensitization alone gave better results than NBAAD and its combination. We had better results from hyposensitization over a period of 1 to 5 years than for less than 1 year or more than 5 years. We conclude that asthmatic children with risk factors should be kept under strict environmental control and given suitable therapeutic regimens to avoid the development of allergic diseases, the slow down of "allergic march", and to avoid intractable asthma. PMID- 2241583 TI - [Nationwide intradermal test with chironomid midge extract in asthmatic children in Japan]. AB - Chironomidea (Insecta) is recently considered one of the most common inhalant antigen in Japan. Intradermal tests with Chironomus plumosus (CP) extract were undertaken on seven hundred and eighteen asthmatic children aged from 6 to 15 years in 10 areas (11 medical institutions) in Japan. The number of cases who showed positive intradermal tests with CP extract was 200 (27.9%) and the positive rate increased in proportion to their age (p less than 0.005). In each of the 11 medical institutions the positive rates ranged from 12.6% in Akita to 45.5% in Okinawa. There were no significant correlations between the results of the intradermal test with CP and those of RAST, prick test and intradermal test with mite, HD and silk, whereas correlation was noted in the prick test with silk (p less than 0.01). The CP positive asthmatics had significantly more attacks than the CP negative ones in the summer (p less than 0.01). The positive rate of asthmatics living near paddy or farm fields was significantly higher than that of those in urban residential areas (31.3% vs 23.8%, p less than 0.05). Chironomid midge is one of the most common and important allergen in Japan. PMID- 2241584 TI - [Clinical study on bronchial asthma patients whose bronchial hypersensitivity has been improved]. AB - In order to determine which factors would affect the improvement of bronchial hypersensitivity in asthmatic patients, a clinical investigation was performed on 42 cases whose bronchial hypersensitivity had been tested more than two times. The following results were obtained. 1) The numbers of bronchial hypersensitivity improved cases was 16 while there were 26 unimproved cases. There was no statistical difference in age, sex, type of asthma, severity of disease at first visit or type of therapy between the two groups. FEV1.0% in the bronchial hypersensitivity-improved group was significantly higher than that in the unimproved group (p less than 0.01). 2) In the improved group, all cases (16/16) were shown to have become free of symptoms, but this applied to only 38% (10/26) in the unimproved group. 3) In the 26 cases who had become free of symptoms, the improvement index in histamine test and the ratio of improved cases showed a tendency to increase as the period during which the patient showed no symptoms extended. It was suggested that bronchial hypersensitivity in cases with higher FEV1.0% would improve more easily, and that the induction and maintenance of a symptom free state is important for the improvement of bronchial hypersensitivity. PMID- 2241585 TI - [Pollinosis and airborne pollen in Fukuoka City]. AB - We investigated the relation between the incidence of pollinosis and pollen counts in Fukuoka City from 1983 to 1989 to clarify the "cause and effect" relationship and to evaluate the severity of pollinosis in this district. We collected questionnaires on pollinosis from six otorhinolaryngology clinics in our city during the pollination seasons from 1983 to 1989. Cryptomeria j., Cupressaceae and Gramineae pollens, which were sampled with Durham's samples from January to June, were sent from seven sampling locations in our city. The number of pollens was counted in our hospital. The total number of patients with pollinosis over the seven years was 4193. Females were numerous than males by one and a half times. The age group with the highest incidence was the thirties (41.9%), followed by the twenties (19.8%) and forties (18.4%). The incidence of Japanese cedar pollinosis was 92.6 percent and grass pollinosis 30.3 percent of all the patients because 23.0% of them overlapped. We found that the severity of nose and eye complaints and other symptoms of pollinosis in our study was milder than that in Tokyo and other Kanto districts. Annual changes in total pollen counts were remarkable, and a high incidence of Japanese cedar pollinosis was found as total pollen counts of Cryptomeria j. and Cupressaceae increased in Fukuoka City. PMID- 2241586 TI - [Studies on antibiotic skin testing]. AB - Commercially available antibiotics for injection are supplied with test ampules. Users are instructed to dissolve them to make 300 micrograms/ml solution for intradermal pretests to avoid allergic reactions. Sometimes this concentration is too low to prevent anaphylactic reactions. In the present study, we tried to find the maximum concentration for the intradermal tests which would have high sensitivity without giving nonspecific, false positive reactions. We investigated intradermal tests with cephalothin (CET) in a patient who suffered from anaphylaxis after drip infusion with CET, although she was judged to be negative to CET by the usual intradermal test prior to the infusion. Her CET skin test was negative at a concentration of 150 micrograms/ml and positive at 300 micrograms/ml 6 weeks after anaphylaxis, but negative at 300 micrograms/ml and positive at 1000 micrograms/ml 4 and 7 years after anaphylaxis. Prick tests were always negative, even with the maximum soluble concentration of CET, 200 mg/ml. Nonspecific reactions to intradermal tests at concentrations as high as 1000 micrograms/ml were examined with 20 kinds of penicillins and cephems in 51 healthy subjects without histories of drug allergies. Very few false positive reactions were observed, except in 5 out of 24 cases with cefotiam. Intradermal tests at 3000 micrograms/ml, however, frequently resulted in nonspecific reactions. We conclude that 1000 micrograms/ml, not 300 micrograms/ml solutions should be used for intradermal tests to prevent allergic reactions to the injection of antibiotics. PMID- 2241587 TI - [A case of suspected allergic granulomatosis and angiitis with a rapid clinical course of paraplegia]. AB - A 68-year-old man with suspected allergic granulomatosis and angiitis is reported. He had received 10 mg of prednisolone daily since July 1988 for asthma. He abruptly developed muscle weakness of the lower extremities, followed two days later by paraplegia. Six days after the onset of the muscle weakness, he was hospitalized. He showed disturbance of recent memory, disorientation, neck rigidity, paraplegia, mild muscle fasciculation and hypesthesia. He also showed paralytic ileus. Laboratory findings showed leukocytosis (24580/mm3), eosinophilia (56% of the peripheral white blood cells and 19% of the cells in the cerebrospinal fluid), on erythrocyte sedimentation rate of 31 mm/h, and the IgE level of 1200 IU/ml. The ECG showed loss of the r-wave in V1 and V2. A granulomatous lesion anterior to the spinal cord was found on myelography and MRI. Prednisolone was given at a dose of 60 mg daily resulting in improvement of the clinical symptoms and eosinophilia. There was disappearance of the granuloma on MRI performed after prednisolone therapy. Despite the severe manifestation of allergic granulomatosis and angiitis, prednisolone therapy had a marked effect in this patient. The granulomatous lesion anterior to the spinal cord shown by MRI suggested an eosinophilic granuloma, and may have been the etiology of some of the neurological symptoms. PMID- 2241588 TI - Participation of granulocyte-macrophage colony stimulating factor, interleukin-1 and dendritic cells in concanavalin A-induced T cell responses in human. AB - The effects of IL-1 and GM-CSF on accessory function of macrophages and dendritic cells (DC) in Con A-induced T cell responses were investigated. The accessory cells were separated from adherent cells of human peripheral mononuclear cells. The accessory function of DC was found to be stronger than that of macrophages. IL-1 and GM-CSF significantly enhanced the T cell responses by augmenting the accessory function of DC in a dose-dependent manner (p less than 0.01), whereas these monokines produced no augmentative effects on macrophages, nor facilitated T cell responses without DC. PMID- 2241589 TI - Effective therapy with low dose of oral cyclosporine A and prednisolone for alopecia universalis. AB - Although alopecia universalis is an incurable disease, we have obtained favorable results using a low dose of 2.5 mg/kg of cyclosporine A and 5 mg/day of prednisolone without adverse effects. We report our clinical experience of the treatment of two cases of alopecia universalis. Immunological examinations showed marked changes in the ratio of T cell subsets in peripheral blood. There was an increase of OKT8 positive cells and NK cells, reduction of IL-2R positive cells. These immunological changes following recovery from alopecia suggest a correlation between immunological disorders and the pathogenesis of this disease (alopecia universalis). PMID- 2241590 TI - Powerful or powerless: nurses in the work environment. PMID- 2241591 TI - Leadership in nursing--what do you think? PMID- 2241592 TI - [Ranitidine in duodenal ulcer. A Brazilian multicenter trial with a single daily dose]. PMID- 2241593 TI - [Is it necessary to perform routine intraoperative cholangiography during cholecystectomy?]. AB - The intraoperative cholangiography was carried out in 361 patients with gallstone disease. In 293 (81.16%) patients cholangiography was normal, in 68 (18.83%) was abnormal. Thirty-six (9.97%) patients had pre-operative asymptomatic common bile duct calculi and 20 (5.54%) patients had confirmed suspect of common bile duct calculi during cholangiography. Twelve (3.32%) patients were false-positive and one (0.27%) was false-negative. It is discussed the value of routine intraoperative cholangiography in patients with gallstone disease. PMID- 2241594 TI - [Non-coronary chest pain: esophageal evaluation in 27 patients]. AB - The authors analyse the clinical features of 27 patients with non-coronary chest pain. They applied specific questionnaire and used esophageal function tests. The pain features were very similar to coronary patients, but there was a strict relationship with emotional stress. Esophageal symptoms were found in about 50% of patients. Eighty-five, one percent of the patients, presented with some abnormalities; 33.3% of the total group with esophagitis and 66.6% with motor disorders; some patients presented overlapping pictures. Three patients had duodenal ulcer. The patients were classified as having pain of proved (18.5%), or suspected (66.6%) esophageal origin. Twenty of these patients were followed and those with esophagitis and/or duodenal ulcer had a good response to specific treatment. The author stress the importance of showing the patients the benign nature of this disease. In the present group of patients, the actual diagnosis was more important in obtaining good therapeutic response than classifying the pain as above. PMID- 2241595 TI - [Single nocturnal dose of ranitidine in the treatment of duodenal ulcer: results of an open multicenter, comparative trial]. AB - This prospective multicentric randomized open trial was designed to evaluate the efficacy of ranitidine 150 mg bid vs 300 mg nocte in the short-term (4 weeks) treatment of duodenal ulcer in 15 Brazilian centers. On the basis of a randomization table 190 patients with endoscopically confirmed duodenal ulcer were allocated to receive either ranitidine 150 mg bid (94 pts) or 300 mg nocte (96 pts). The 2 treatment groups were well matched for age, sex, duration of ulcer disease, number and size of ulcers, duration of current episode, intensity of ulcer pain, alcohol and coffee intake and smoking habits. They were endoscopically controlled at the end of the 4 weeks. At 4 weeks 78 of 94 patients (83.0%) had their ulcers healed with the 150 mg bid regimen as opposed to 79 of 96 patients (82.3%) allocated to the 300 mg nocte dosage. This difference was not statistically significant. Ulcer symptoms diminished with treatment in both groups. The tolerability and compliance was excellent in both groups. The results show that ranitidine 300 mg nocte is as effective in the short-term treatment of duodenal ulcer as ranitidine 150 mg bid. Considering the greater simplicity of administration enhancing patient compliance, the treatment with 300 mg nocte is preferable. PMID- 2241596 TI - [Carcinoid of Meckel's diverticulum. Report of a case and review of the literature]. AB - The presence of carcinoid tumor in a Meckel's diverticulum is a rare entity. This report describes a 56-year-old man who was admitted to hospital with symptomatic gallbladder stones. At laparotomy the gallstones were confirmed and routine exploration of the peritoneal cavity identified a small bowel diverticulum about 60 cm of the ileocecal valve. Cholecystectomy and resection of a small bowel segment containing the diverticulum were performed. Histology revealed carcinoid tumour in Meckel's diverticulum. PMID- 2241597 TI - [Menetrier's disease in children: report of 3 cases and review of the literature]. AB - Three cases of Menetrier's disease in childhood are reported and 38 other cases previously described in the literature are reviewed. The disease manifests in children as a protein-losing gastropathy and a characteristic hypertrophic gastric rugae is demonstrated by upper gastrointestinal radiographs or endoscopy. In contrast to the usual chronicity of the disease in adults, the course is usually benign in children and the symptoms resolve spontaneously in weeks or months. The possible etiology and differential diagnosis are discussed. Menetrier's disease in children may be more common than report. PMID- 2241598 TI - Effectiveness of push/pull hemodiafiltration using large-pore membrane for shoulder joint pain in long-term dialysis patients. AB - Long-term hemodialysis (HD) patients complaining of shoulder joint pain were treated by HD and by push/pull HDF using high-flux synthetic membranes with large pores (Asahi PAN 20CX2) for 2 weeks. The results showed no significant difference in Kt/Vurea between HD and push/pull HDF. Nevertheless, reduction of the plasma beta 2-microglobulin was greater during push/pull HDF than during HD. These findings can be explained by far more convective flux in push/pull HDF than in HD: nearly 30 L during push/pull HDF vs. 3 L during HD. In the present study, there was no alleviation of the shoulder joint pain during HD treatment, whereas marked relief of the symptom was found during push/pull HDF treatment. Since the two treatment modalities differ simply in their efficiency in removing larger molecular weight substances, the joint pain alleviation effected by push/pull HDF could well be ascribed to elimination of an unknown larger molecular weight substance causing this symptom. However, a considerable amount of beta 2 microglobulin was removed both by HD and push/pull HDF. Therefore, the substance causing the joint pain might be larger than beta 2-microglobulin. PMID- 2241599 TI - Gas supply across membranes in bioreactors for hepatocyte culture. AB - The conditions required for hepatocyte cultures is a main topic in the development of bioreactors for hybrid liver support systems. The detoxification of ammonia and the synthesis of urea due to primary isolated hepatocytes was measured in order to compare two different models of gas supply in bioreactors: (a) indirect medium oxygenation and (b) direct membrane-contact oxygenation of the hepatocytes using polypropylene membranes. Increasing oxygen pressure promoted cell function. At day 6 of culture, urea synthesis was 0.8 +/- 0.3 mM in 21% of O2 cultures and 1.5 +/- 0.1 mM in oxygenated cultures. Alkalosis due to CO2 loss decreased ammonia metabolism. The direct membrane-contact oxygenation resulted in enhanced cell metabolism in comparison to medium oxygenation: urea synthesis at day six was 1.42 +/- 0.2 mM in 21% O2 cultures. Polypropylene oxygenation membranes proved to be sufficient for hepatocyte adhesion. Two functions can be integrated in one element in liver support systems using the investigated polypropylene membrane and the direct membrane-contact oxygenation: oxygenation with physiological oxygen pressure in bioreactors due to gas supply across the membrane and adhesion of hepatocytes in bioreactors on the membrane. PMID- 2241600 TI - Selective removal of anti-acetylcholine receptor antibodies and IgG in vitro with an immunoadsorbent containing immobilized sulfathiazole. AB - Adsorption therapy, which treats the autoimmune disease by the selective removal of pathogenic substances from the blood, is an active subject. In this therapy, bioactive molecules such as antigen, antibodies and protein A are usually used as affinity-ligands. The disadvantages of using these substances as affinity-ligands are the availability, sterilizability, and ability to cause antigenic reactions. After surveying hundreds of synthetic compounds, it was found that polyacrylic beads [Eupergit C (EC)] immobilized covalently with sulfathiazole (ST) are an ideal biomimetic ligand for the selective adsorption of IgG (24.3 +/- 0.4 mg IgG/g wet beads). In an in vitro study, this adsorbent selectively removed the antiacetylcholine (AChR) receptor antibody of myasthenia gravis (MG) patients. Further experiments demonstrated that the Fab fragment was adsorbed three times more efficiently than the Fc fragment of IgG. PMID- 2241601 TI - A large-scale magnetic separator for selective cell separations with paramagnetic microbeads. AB - An improved magnetic separator has been developed for use in large-scale cell separations. This separation method uses paramagnetic microbeads coated with antibodies that selectively bind to target cells. The magnetic separator attracts the microbead-target cell aggregates and holds these aggregates at its surface while the suspending fluid and nontarget cells flow past. The optimum separator design was determined to be two magnetic assemblies in series along with a peristaltic pump. The assemblies consist of neodymium-iron-boron magnet bars sandwiched between steel bars (magnetic pole pieces). The size and pole spacing of the two magnetic assemblies are designed to be different, so that the first assembly, which captures greater than 99.99% of the microbeads, has good magnetic reach-out and a high magnetic holding force at its surface, while the second assembly has an even higher magnetic holding force at its surface. Studies show that the separator can remove 1 x 10(10) microbeads from a suspension of red blood cells processed at a flow rate of 9 ml/min, so that no microbeads are detected in the effluent. PMID- 2241602 TI - Quantification of perivalvular thrombus formation in blood pumps by polar coordinate mapping. AB - A polar coordinate mapping technique (PCMT) to quantitatively describe perivalvular thrombus formation was applied in the examination of prosthetic valves from paracorporeal assist devices. The method begins by photographing the upstream and downstream views of the freshly retrieved valves using transparency film. The valve images are then projected onto 10 x planforms of the valves, and the boundaries of the observable thrombi are traced. The radial thrombus length is then measured at 5 degrees increments and plotted on Cartesian coordinates as a function of polar coordinate. Mean radial thrombus length and incidence of thrombus are calculated. Statistical analysis can then be used to test for differences in the length, incidence, and pattern of thrombus formation between test groups. The effect of valve selection, anti-coagulant regime, and other factors that influence thrombus formation can be quantitatively compared with the PCMT. Consequently, the PCMT could be a valuable assessment tool for efforts being made to reduce thrombosis in prosthetic blood pumps. PMID- 2241603 TI - Endothelial cell seeding of small diameter vascular grafts. AB - This study examines, under flow conditions, the adhesion of endothelial cells to 3 mm diameter fibronectin (Fn)-coated expanded polytetrafluoroethylene (PTFE) vascular grafts. Cultured ovine carotid artery endothelial cells were labelled with 35S-methionine. The grafts were seeded with endothelial cells (1.5 x 10(6)/ml) by rolling for 1 h at 37 degrees C and then either cultured to confluence for 48 h or flow tested immediately. Cell attachment to grafts (n = 5) was evaluated in an in vitro flow circuit, using flows of up to 330 ml/min. Ex vivo studies (n = 5 grafts) were conducted without anticoagulant using autologous cells in a sheep model. Grafts were inserted into an externalized carotid-jugular shunt and exposed to blood flows of approximately 150 ml/min for 3 h. One hour seeded and 48 h cultured grafts demonstrated greater than 95% cell retention following in vitro flow studies. Ex vivo studies of 48 h cultured grafts gave endothelial cell retention of 81% with no sign of thrombogenicity. Furthermore, a preliminary 24 h ex vivo study has shown greater than 95% retention. This study demonstrates the firm attachment of seeded endothelial cells to Fn-coated PTFE grafts in the sheep model. PMID- 2241604 TI - A new multilayered composite hollow fiber membrane for artificial lung. AB - The gas transfer performances in a gas/membrane/liquid system were investigated in detail with various membranes. It was found that the oxygen flux in the gas/membrane/liquid system was saturated when the oxygen flux (Fg-g) in the gas/membrane/gas system became more than 1.0 x 10(-5) cm3 (STP) cm-2s-1cm Hg-1 (Fcg-g). This was explained as follows: The resistance of a boundary layer at liquid phase is dominant, i.e., the membrane resistance is negligible in the region of Fg-g which is greater than Fcg-g. Consequently, Fg-g of the membrane should be designed to be greater than Fcg-g, in order to satisfy the gas transfer performance required for blood oxygenation. On the basis of the results above, we have developed a new three-layered composite hollow fiber membrane (MHF) consisting of an ultrathin polyurethane layer supported between two microporous polyethylene layers to prevent serum leakage. It was shown through the evaluation in vitro that MHF had good gas transfer performances for long-term perfusion, and no serum leakage was observed. These characteristics suggest that MHF is quite suitable for long-term usage such as extracorporeal membrane oxygenation (ECMO). PMID- 2241606 TI - Transesophageal echocardiographic findings of intracardiac events during cardiac assist. AB - Transesophageal echocardiography (TEE) is an easy, noninvasive and reproducible method for evaluation of left ventricular function, coronary flow patterns, and intracardiac blood flow patterns during cardial assist. TEE facilitated better management of the patients with LVAD and gave us the various information: (a) Observing the drawing catheter tip by TEE, it could be settled just above the mitral orifice to obtain the maximum bypass flow; in addition, dislocation of the catheter tip could be easily diagnosed. (b) The intracardiac thrombus could be clearly detected by TEE; it was removed without complications, weaning from left ventricular assist device (LVAD). (c) The left ventricular wall motion was periodically observed. The end systolic LV diameter (Ds) was decreasing and fractional shortening (%FS) was increasing as the natural heart recovery. Additionally, the preejection period (PEP) and the ejection time (ET) were measured. The ratio of PEP/ET was decreasing gradually. Ds did not alter with preload change during on-off testing unlike the other parameters. Ds seems to be the most reliable parameter for the natural heart recovery within certain amounts of bypass flow. (d) The flow velocity in the left anterior descending coronary artery could be measured by transesophageal Doppler method; it was clinically shown that counterpulsation produced a larger amount of coronary blood flow than copulsation. PMID- 2241605 TI - Noise level and perception of the closing click after heart valve replacement with St. Jude Medical and Bjork Shiley Monostrut prostheses. AB - The metallic click generated by the closure of mechanical heart valve prostheses may severely bother patients, but generated sound energy and the extent of complaints after implantation are not known. In 62 patients, after valve replacement with St. Jude Medical (SJM) (n = 35) and Bjork Shiley Monostrut (BSM) (n = 27) prostheses, sound energy was recorded with a calibrated noise level analyzer at 5, 10, and 100 cm distance from patients and correlated with their complaints. At a distance of 100 cm, the BSM valves produced a significantly higher sound pressure level, 30.5 +/- 5 db(A), compared to the SJM valves, 24.1 +/- 4 db(A) (p = 0.0001). There was no significant difference at shorter distances. After splitting into frequency bands the highest sound pressure levels were observed in the high frequency ranges (8 to 16 kHz) representing the metallic click. BSM valves produced higher sound levels in all frequency ranges at 1 m distance. Seventy-three percent of all patients were aware of the noise generated by the valve; 20% had disturbed sleep; and 26% preferred a less noisy valve type. Twelve of 27 patients with BSM valves wanted less noisy valves, whereas only 4 of 35 patients with SJM valves wished to have a less noisy valve type (Chi-square p = 0.003). In patients who could hear their valve measured, sound level was higher than in patients who could not. In 9 of 27 patients with BSM (33%), versus 3 of 35 with SJM prostheses (9%), the clicking caused sleep disturbances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241607 TI - Analysis of clinical factors for survival after left and biventricular bypass using centrifugal pump following open heart surgery in infants and adults. AB - A total of eight patients, including three infants, received left or biventricular assist using centrifugal pump (CFP) following open heart surgery. Three infants, aged 9-11 months and with complex cardiac lesions, were supported by left heart bypass (LHB) using pediatric type CFP for 63 h, 64 h, and 13 days. All were weaned from LHB, but long-term survival was not obtained, mainly due to complications. In five adult patients, LHB alone was used in three, and biventricular support in two for 33-240 h with three survivals. The factors related to unsuccessful recovery were delayed start of support and multiorgan failure. PMID- 2241608 TI - Glued carbon fiber electrodes for diaphragm pacing. AB - Carbon fibers with fibrin glue were used as electrodes for diaphragm pacing. The electrodes were applied to three mongrel dogs and the effectiveness was tested. The carbon leads were glued to phrenic nerves by means of the fibrinogen and thrombin bilaterally. The tidal volumes and threshold current level for stimulation were measured at various time up to 9 weeks after implantation. Effective contraction of diaphragm were observed for 9 weeks. By using this electrode, the exfoliation of the nerve is not necessary, the nerve can be maintained in an intact state, and the risk of the implanting operation can be minimized. PMID- 2241610 TI - Strokes associated with cocaine use. PMID- 2241609 TI - Rolling chair sign. PMID- 2241611 TI - The practice of neurology. PMID- 2241612 TI - The influence of hyperglycemia and diabetes mellitus on immediate and 3-month morbidity and mortality after acute stroke. AB - Fasting serum glucose, glycosylated hemoglobin, and fructosamine concentrations were determined in 304 consecutive subjects admitted with acute stroke, within 48 hours of ictus. Based on the medical history and these results, subjects were divided into known diabetics, newly diagnosed diabetics, subjects with stress hyperglycemia, and nondiabetics. The type of stroke was classified as lacunar infarct, cerebral infarct, or intracerebral hemorrhage, based on clinical examination by a neurologist and computed tomographic brain scan and/or autopsy. Immediate and 3-month outcomes were examined in relation to (1) fasting glucose, glycosylated hemoglobin, and fructosamine levels by stroke subtypes, and (2) glucose tolerance categories by stroke subtypes. A high fasting glucose level was associated with an increased mortality, but this was observed only among patients with intracerebral hemorrhage. Patients with stress hyperglycemia, but not diabetics, had increased mortality. In spite of having similar glucose concentrations to those patients with stress hyperglycemia, diabetics did not have a worse outcome compared with nondiabetics. It is concluded that the association between glucose concentration and outcome is a reflection of stress relating to stroke severity, rather than a direct harmful effect of glucose on damaged neurons. PMID- 2241613 TI - Circadian variation in onset of acute ischemic stroke. AB - A circadian pattern for the onset of myocardial and cerebral infarction has been identified. To evaluate this phenomenon further, we analyzed prospectively collected data from 151 patients with acute ischemic stroke. The number of strokes per 6-hour period were the following: midnight to 6 AM, 20 (13%); 6 AM to noon, 86 (57%); noon to 6 PM, 21 (14%); and 6 PM to midnight, 24 (16%). This pattern was not affected by previous use of aspirin. The most frequent time of onset was 6 AM to noon for all subgroups of ischemic stroke: small artery, 71%; cardioembolic, 62%; large artery atherothrombotic, 57%; large artery atheroembolic, 46%; and "other" or unknown cause, 40%. We also investigated the time between awakening and stroke onset in 145 patients and found that 24% of ischemic strokes occurred within the first hour after awakening. Our data demonstrate that an early morning peak exists for all subtypes of stroke. Our data also suggest that the most critical period is the first hour after awakening. PMID- 2241614 TI - Nontraumatic coma. Glasgow coma score and coma etiology as predictors of 2-week outcome. AB - In 1987 and 1988, we carried out a prospective study of patients older than 10 years with nontraumatic coma in the intensive care units of Columbia-Presbyterian Medical Center, New York, NY. Of 188 patients with Glasgow Coma Scale (GCS) determinations within 72 hours, 61% were dead or in persistent coma by 2 weeks from onset. Age, sex, and ethnicity did not influence outcome. The 2-week outcome for patients with initial GCS of 3 to 5 was 14.8% awake; 85.2% were dead or in persistent coma. For the GCS 6 to 8 group, 53.1% were awake and 46.9% were dead or in persistent coma. Hypoxic or ischemic coma had the worst 2-week outcome (79% dead or comatose); coma caused by metabolic disease or sepsis (68%), focal cerebral lesions (66%), and general cerebral diseases (55%) were intermediate, while drug-induced coma had a favorable outcome (27% dead or comatose). The independent predictors of 2-week outcome were the first GCS and drug-induced coma. The predicted probability of waking at 2 weeks was eight times better for drug-induced coma than other causes when GCS was held constant. Patients with an initial GCS score of 6 to 8 were seven times more likely to waken than those with a score of 3 to 5. The motor subscore alone was a significant independent predictor of 2-week outcome. Modification of coma score to include etiology may give more accurate predictions of 2-week outcome after nontraumatic coma. PMID- 2241615 TI - Quantitative electroencephalographic correlates of cognitive decline in normal elderly subjects. AB - We obtained a topographic computer analysis of the electroencephalogram in 53 normal elderly subjects. Normal aging was not associated with an increase in slow (delta) activity. However, cognitive performance correlated positively with fast (beta) activity particularly in frontal leads, even after controlling for age, education, occupation, and medication. Five subjects who showed early signs of cognitive decline, had all a marked reduction in beta activity suggesting that this may be an early indication of intellectual loss. PMID- 2241616 TI - Screening for early dementia using memory complaints from patients and relatives. AB - This study examined whether the subjective impression of memory function might differentiate healthy elderly subjects from patients with memory complaints, and whether memory complaints differed between patients with and without a dementing illness. Both self-assessment and relatives' responses on a new memory questionnaire differentiated patient groups from control subjects. The relatives' form measuring deterioration in memory function over time identified dementing individuals from those with non-dementing causes for their memory complaints. Factor analysis indicated that patients' memory complaints correlated with depression rather than objective memory performance, while relatives' ratings correlated with objective memory scores, not depression. Stepwise discriminant function analyses showed that objective memory testing greatly improved specificity but not sensitivity of the subjective memory questionnaire alone. PMID- 2241617 TI - Magnetic resonance imaging of the human lateral geniculate body. AB - We used magnetic resonance imaging to map the human lateral geniculate body. The optimal imaging plane was determined by obtaining axial and coronal scans in two normal brains obtained at autopsy. The brain specimens were then sectioned and individual slices were compared with matching magnetic resonance images. After the lateral geniculate body was identified using this correlative anatomic approach, the nucleus was imaged in four normal subjects. PMID- 2241618 TI - Variable expressivity in familial restless legs syndrome. AB - A 62-year-old man with a 20-year history of excessive daytime somnolence and kicking during sleep was an obligate carrier of the restless legs syndrome gene because his paternal grandfather, father, and all three of his children had symptoms of restless legs syndrome. The patient himself, however, denied motor restlessness after a careful and exhaustive medical history and he was originally believed to have periodic movements in sleep without restless legs. Close clinical observation did reveal nighttime motor restlessness, although the patient continued to deny its importance. Polysomnography showed frequent periodic movements in sleep. We conclude that there can be variable expressivity of the clinical features in familial restless legs syndrome and that there are probably some relatively nonrestless patients with prominent periodic movements in sleep who are carriers of the restless legs syndrome gene. Some sleep disordered patients who are believed to have only periodic movements in sleep may have a forme fruste of autosomal dominant restless legs syndrome. If one does not examine these patients carefully at night and take an adequate family history, one may miss the diagnosis of restless legs syndrome. PMID- 2241619 TI - Asthma and eczema in children born to women with migraine. AB - Migraine and asthma have been reported to occur in the same person more commonly than would be expected if they are independent. The large Collaborative Perinatal Project provided an opportunity to see if children born to women with migraine or with the group of disorders characterized by asthma and/or allergies were more likely to manifest asthma or eczema in the first 7 years of life. Among children whose mothers had neither migraine nor asthma/allergies, 3.2% had asthma. Of children whose mothers had migraine, but not asthma/allergies, more than 6% had asthma. The risk of asthma among children born to women who had both migraine and asthma/allergies was greater than the risk associated with each maternal disease. The risk of eczema in children was not appreciably influenced by the mother's propensity to migraine or asthma/allergies. The results of this first study of migraine in one generation and asthma in the next lead to the conclusion that the two disorders are probably related. PMID- 2241620 TI - Hemifacial spasm in Rochester and Olmsted County, Minnesota, 1960 to 1984. AB - The incidence of hemifacial spasm in residents of Olmsted County, Minnesota, was studied by reviewing the medical records of patients residing in the community between 1960 and 1984. The average annual incidence rate was 0.74 per 100,000 in men and 0.81 per 100,000 in women, age-adjusted to the 1970 US white population. The average prevalence rate was 7.4 per 100,000 population in men and 14.5 per 100,000 in women. The incidence and prevalence rates were highest in those from 40 to 79 years of age. PMID- 2241621 TI - Temporoparietal cortex in aphasia. Evidence from positron emission tomography. AB - Forty-four aphasic patients were examined with (F18)-fluorodeoxyglucose positron emission tomography in a resting state to determine whether consistent glucose metabolic abnormalities were present. Ninety-seven percent of subjects showed metabolic abnormalities in the angular gyrus, 89% in the supramarginal gyrus, and 87% in the lateral and transverse superior temporal gyrus. Pearson product moment correlations were calculated between regional metabolic measures and performance on the Western Aphasia Battery. No significant correlations were found between the Western Aphasia Battery scores and right hemisphere metabolic measures. Most left hemisphere regions correlated with more than one score from the Western Aphasia Battery. Temporal but not frontal regions had significant correlations to the comprehension score. The left temporoparietal region was consistently affected in these subjects, suggesting that common features in the aphasias were caused by left temporoparietal dysfunction, while behavioral differences resulted from (1) the extent of temporoparietal changes, and (2) dysfunction elsewhere in the brain, particularly the left frontal and subcortical areas. PMID- 2241622 TI - The Marinesco-Sjogren syndrome examined by computed tomography, magnetic resonance, and 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography. AB - The Marinesco-Sjogren syndrome is an autosomal recessive degenerative disorder characterized by congenital cataracts, cerebellar ataxia, spasticity, mental deficiency, and skeletal abnormalities. We studied two adult siblings with Marinesco-Sjogren syndrome using anatomic and metabolic brain imaging techniques to characterize the pattern and nature of abnormalities in the brain. Computed tomographic and magnetic resonance imaging showed diffuse brain atrophy of mild to moderate degree, involving primarily the white matter of the cerebrum, cerebellum, brain stem, and cervical spinal cord. The pattern of atrophy resembled that seen in diffuse leukoencephalopathies. Measurements of local cerebral glucose metabolic rates with positron emission tomography revealed no statistically significant differences from normal control subjects in most regions, but metabolic rate was decreased in the thalamus in one patient. The findings support a diffuse white matter disorder in Marinesco-Sjogren syndrome. PMID- 2241623 TI - Unusual cerebral manifestations in hereditary fructose intolerance. AB - Five children with hereditary fructose intolerance developed symptoms of neurological impairment. In three of them, neurological involvement was related to the acute hepatic toxicity of fructose (hypoglycemia, abnormal coagulation, cardiovascular collapse); in the other two, such a relationship could not be demonstrated. Neurological impairment is not classic in hereditary fructose intolerance, but its occurrence in the acute phase of the disease is possible and does not constitute an argument against the diagnosis. PMID- 2241624 TI - Background review and current concepts of reperfusion injury. AB - We define the concept of reperfusion injury, and we present a background chronology of experimental work supporting and questioning this concept. We identify several new influences, such as current clinical interest in thrombolytic therapy for acute ischemia of heart and brain and the growing recognition of endothelium as a regulator of homeostasis. We propose that these influences will encourage a reexamination of reperfusion injury as a factor in the ultimate outcome of tissue exposed to reversible ischemia. We briefly discuss the major mechanisms presently implicated in reperfusion injury--loss of calcium homeostasis, free radical generation, leukocyte-mediated injury, and acute hypercholesterolemia. PMID- 2241625 TI - Aplasia cutis congenita and arteriovenous fistula. Case report and review. AB - We describe a child with congenital aplasia cutis congenita of the scalp and an occult giant posterior fossa arteriovenous fistula. Previous case reports of central nervous system malformations associated with aplasia cutis congenita are reviewed. The exact incidence of such malformations is unknown. All patients with aplasia cutis congenita should undergo a neurologic evaluation, and their families should be examined for similar lesions. Early central nervous system imaging and other workup may be required, especially if plastic surgery in the head region is being planned. PMID- 2241626 TI - Retrovirus from human T-cell leukemia virus type I-associated myelopathy is the same strain as a prototype human T-cell leukemia virus type I. AB - A retrovirus was isolated from a T-cell line that was established from lymphocytes in the cerebrospinal fluid of a patient with human T-cell leukemia virus type I-associated myelopathy (HAM), and its genome was sequenced. The nucleotide sequence of the 3' half of the total genome was identical in 99.5% of the nucleotides to that of the prototype human T-cell leukemia virus type I that was derived from a patient with adult T-cell leukemia. These results indicate that the same retrovirus human T-cell leukemia virus type I is associated with both a neurological disease, HAM, and a lymphoproliferative disease, adult T-cell leukemia. PMID- 2241627 TI - Union amalgamations--what happens to nurses? PMID- 2241628 TI - About a peculiar disease. Interview by Gay Hudson. PMID- 2241629 TI - Uniform view. PMID- 2241630 TI - A visit to the Nightingale Museum. PMID- 2241631 TI - Occupational health v occupational diseases. PMID- 2241632 TI - The third age. How to get the best out of your SMTs. PMID- 2241633 TI - Metoclopramide--acute dystonic reactions. PMID- 2241634 TI - A nursing narrative. PMID- 2241635 TI - Current status of nuclear power in the United States and around the world. AB - Nuclear energy's share of the world electricity market has been growing over the past 35 years. In 1989, eight generating units entered commercial operation abroad and three new units were licensed in the U.S. In early 1990, Mexico became the 26th country to produce electricity from nuclear power. Currently the 426 operating reactors supply one sixth of the world's total electrical capacity. Fourteen countries have now operated nuclear plants for 20 or more years. Since 1980, France has been the leader in the use of nuclear power and currently generates three quarters of its electricity from 54 nuclear plants. The U.S. has 112 nuclear plants, the largest number of any country in the world. These plants satisfy almost 20 percent of U.S. electrical energy requirements. Last year Three Mile Island, the would-be icon for everything that is wrong with the nuclear industry was rated as the most efficient nuclear plant in the world. The worldwide trend toward acceptance of nuclear is improving slightly, but many political and societal issues need to be resolved. Whereas recent polls indicate that a majority of the people realize nuclear must be a major contributor to the energy mix of the future, many are reluctant to support the technology until the issue of waste disposal has been resolved. Fears of another Chernobyl, lack of capital, and a new anti-nuclear campaign by Greenpeace will keep the nuclear debate alive in many countries. Additional stumbling blocks in the U.S. include the need to develop a new generation of improved reactor designs which emphasize passive safety features, standardized designs and a stream-lined federal licensing process. Nuclear power is really not dead. Even environmentalists are starting to give it another look. A nuclear renaissance will occur in the U.S. How soon or under what conditions remain to be seen. The next crisis in the U.S. will not be a shortage of energy, rather a shortage of electricity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241636 TI - Determination of total body water by Fourier transform infrared analysis. AB - A new technique for determining body water using deuterium isotope dilution and Fourier transform infrared (FTIR) analysis is described. The advantages of the FTIR over conventional dispersion and filter infrared instruments include greater flexibility through computer controlled operations and availability of 'on-line' analytical software. The technique was further improved by the development of a simple procedure for determining D2O concentration in untreated serum samples. A validation study of six normal adults showed that the fat-free-mass determined from the deuterium-space (total body water) correlated well with the results obtained by total body nitrogen (r = 0.997), total body potassium (r = 0.996) and anthropometric (r = 0.995) measurements. PMID- 2241637 TI - The production of body analogs for use in radiation physics. AB - Bone, muscle and lung analog materials have been produced in-house, and dosimetry phantoms have been produced. A method using computed tomography (CT) has been developed to check that the analogs produced match the radiation properties of body tissues. The relative electron densities and ratio of electron cross sections are calculated from elemental compositions of the analogs. Using these data the theoretical CT numbers are calculated and these numbers are compared with experimental CT numbers for the analogs produced. The experimental CT numbers are found by scanning the samples on a Siemens DRH CT scanner. Results show the maximum difference between theoretical and experimental CT numbers for the analogs is 18 Hounsfield units, which relates to a delta NCT of less than 1%. Comparison of analog CT numbers with CT numbers for the related patient tissues also shows a close match. PMID- 2241638 TI - Dual photon absorptiometry using a gamma camera. AB - The most common technique for bone mineral densitometry is Dual Photon Absorptiometry with a dedicated scanning device. In principle, a gamma camera could be adapted to perform the same function, but little work along these lines has been reported in the literature. Tests made using a standard gamma camera with a 153Gd source at the focus of a magnifying collimator show that satisfactory results can be obtained on water/aluminium phantoms. A calibration is used to help ensure long term precision and stability. Measurements made using the same equipment but 241Am/99mTc sources gave poor results. PMID- 2241639 TI - Comparative evaluation of chargers for wheelchair gel cell batteries. AB - This study was undertaken as part of our ongoing work to upgrade wheelchair quality. Laboratory tests were conducted to determine which battery chargers would ensure that the user's batteries are fully charged each night and also ensure that the battery lifetime was not diminished. Five commercial chargers were tested on a standardised pair of gel cell batteries of a type commonly used to power wheelchairs. Results of this study indicate a clear preference between chargers. As a result, we have changed the chargers we purchase. We anticipate that our clients will now experience longer life from their wheelchair gel cell batteries. PMID- 2241640 TI - Average occupational exposures. PMID- 2241641 TI - Percutaneous surgery and audit: a timely evaluation. PMID- 2241642 TI - Surgical options in ulcerative colitis: role of ileo-anal anastomosis. PMID- 2241643 TI - Criteria audit of percutaneous nephrolithotomies. AB - A criteria audit of percutaneous nephrolithotomy management is reported. One hundred consecutive patients who underwent percutaneous stone removal over a 3 year period were examined. An analysis of the cases of this relatively new surgical procedure are presented. The audit demonstrated the surgeons' learning curve, the current standards achieved and changes in patient admission rate. Criteria auditing was used and assessed as a quality assurance activity. PMID- 2241644 TI - Surgical analysis and biological behaviour of 2277 basal cell carcinomas. AB - A total of 2277 basal cell carcinomas (BCC) treated by surgical excision over a twenty-year period has been followed and analysed into clinical and histopathological type. This paper documents the incidence of different BCC types and points to the importance of the infiltrating, morphoeic and multifocal types. Many BCC are of one homogeneous histopathological type, although others have important secondary characteristics which may not be obvious clinically. We reserve the use of the word 'infiltrating' for BCC types which show microscopically the following characteristics: areas with lack of palisading; small cell clumps; and spiky thin cords of cells projecting out with loose stroma. These may penetrate far and wide along tissue planes and nerves, producing recurrence and spread, despite apparently adequate excision. The infiltrating BCC may also occur secondarily with other primary BCC types, accounting for their--at times--unexpectedly severe effects. PMID- 2241645 TI - Early gastric cancer. AB - Eighteen cases of 'early gastric cancer' have been managed over a 14-year period. This represents only 3.5% of all patients diagnosed as having adenocarcinoma of the stomach. The symptoms of early gastric cancer are similar to those of benign peptic ulcer disease and differ from those of invasive disease. The pathology of the lesions is described and the morphology shown to be similar to that seen in Japan. The overall 5-year survival rate is 82% but no patient has developed recurrence within 5 years of surgery, confirming the biological behaviour of the lesion to be identical to that noted by Japanese researchers. PMID- 2241646 TI - Patterns of surgical treatment of breast cancer in Victoria. AB - We analysed data on admissions to Victorian public hospitals for surgical treatment of breast cancer over the period July 1985 to December 1988. Of the 2993 women admitted, 28.7% received breast-preserving surgery. The probability of a woman being treated conservatively was dependent on age, with women aged less than 50 or more than 70 years more likely to receive breast-preserving surgery than women aged 50-69. There was an age-specific change, of marginal statistical significance, in the proportion of women receiving breast-preserving surgery over the period. The public hospitals admissions database is a potentially useful means of monitoring patterns of surgical treatment. PMID- 2241647 TI - Fine needle biopsy of thyroid nodules: the importance of technique. AB - Fine needle biopsy (FNB) is the most accurate method available for the investigation of single thyroid nodules. The exact technique employed, however, varies considerably among clinicians: in our institution the incidence of 'inadequate' specimens produced ranges from only 13 to 62%, depending on the individual performing the biopsy. In a prospective in vivo study, a variety of biopsy techniques employing different gauge needles and differing numbers of passes with and without aspiration were assessed with respect to the quality of cytological specimen produced. Criteria assessed included the number of cells or sheets of cells, cell clumping, blood contamination, amount of colloid, and overall slide quality. Samples obtained with a 21 gauge needle without aspiration consistently gave best individual cell morphology. On the other hand, samples obtained with a 23 gauge needle with five aspirated passes through the nodule gave the highest yield of cells with an acceptable minimal increase in the degree of blood contamination and cell clumping. In order to achieve consistent yields from FNB of thyroid nodules, a combination of these two techniques is recommended. PMID- 2241649 TI - Villous adenomas of the duodenum and an unusual variant. AB - We report two cases of villous adenoma of the duodenum, one arising from the main papilla and the other from the accessory papilla. Both were managed by local resection. In one case endoscopic biopsies and intraoperative frozen sections were negative for carcinoma but histology of the locally resected specimen revealed a focus of invasive adenocarcinoma. Villous adenomas of the duodenum have a high risk of malignant change and foci of carcinoma can be missed on endoscopic biopsy. The literature is reviewed and the clinical, diagnostic, pathological and therapeutic aspects of villous adenomas of the duodenum are discussed. PMID- 2241648 TI - Sessile adenomas of the rectum: a personal series 1974-1984. AB - Sessile (villous) tumours of the rectum are uncommon and individual surgeons are unlikely to have wide experience in their management. A study was made of a unique personal series (AMC) of 104 cases encountered from 1974 to 1984; minimum duration of follow-up was 5 years. Clinically obvious rectal cancers were excluded from the study. Ages ranged from 42 to 89 years (mean 64.9 years) with a male:female ratio of 1.5:1. The commonest clinical presentations of sessile tumours of the rectum were rectal bleeding (45%) and altered bowel habit (38%). Hypokalaemia was a very uncommon presenting symptom (1%). These tumours ranged in longitudinal diameter from 1 to 9 cm, with 66% of cases greater than 3 cm and 33% of cases greater than 5 cm. The incidence of malignancy in sessile adenomas greater than 3 cm (27%) was more than triple that of adenomas less than 3 cm (8%) and the presence of induration on rectal examination was the most reliable clinical indicator of the presence of malignancy. Local transanal diathermy excision was a satisfactory form of treatment for most sessile tumours of the rectum (benign and malignant); especially if they were less than 3 cm (0% recurrence rate). It had the added advantage of preserving the anal sphincter and was possible in a higher proportion of sessile tumours in the lower half of the rectum (89%) than those in the upper half of the rectum (42%). The overall recurrence rate after local transanal excision was 8% for benign sessile adenomas and 33% for those containing invasive carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241650 TI - Review of pyogenic liver abscess at the Royal Adelaide Hospital 1980-1987. AB - Pyogenic liver abscess is an uncommon condition which carries substantial morbidity and mortality if untreated. A review was undertaken of 31 patients who were admitted to the Royal Adelaide Hospital (RAH) between January 1980 and December 1987 and who were diagnosed as having pyogenic liver abscess. The aims of the study were to review the aetiology, current methods of investigation and treatment of the disease, and to formulate a management plan based on the findings. Hypoalbuminaemia, leukocytosis and elevated alkaline phosphatase were the most common findings. Hyperbilirubinaemia was not a usual feature. Computerised tomography (CT) scanning and ultrasound were the most useful imaging modalities in identification of the abscess. The sensitivity of CT scanning in evaluating the size of abscesses was lower than anticipated and this may lead to a higher than necessary rate of surgical drainage. A case is presented to illustrate this. Most abscesses were secondary and frequently due to extension of infection from biliary structures. Diseases causing diminished resistance to bacterial infection had a significant role in the pathogenesis. The overall mortality rate was 25%. Risk factors increasing mortality included advanced age, multiplicity of abscesses, depressed immune status and the presence of complications due to the abscess. Of patients who survived, four were treated with antibiotics alone, eleven with percutaneous drainage and antibiotics, and eight with surgery and antibiotics. We conclude that patients with hepatic abscesses should be managed initially by CT or ultrasound-guided aspiration. If pus is obtained a percutaneous drain should be inserted into the cavity and systemic antibiotics administered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241651 TI - Pancreatitis and pancreas divisum: aetiological and surgical considerations. AB - It has been suggested that acute pancreatitis occurs more commonly in patients with pancreas divisum and that these patients may respond to surgery aimed at improving pancreatic ductal drainage. We have studied the incidence of pancreas divisum in patients referred for endoscopic retrograde cholangio pancreatography (ERCP) and the results of surgical sphincteroplasty in a separate series of such patients. Twenty-three patients with pancreas divisum were identified among 336 successful pancreatograms (Group A), an incidence of 6.8%. The incidence of pancreas divisum in patients having ERCP for documented pancreatitis was 13% (11 of 86) compared with 4.8% (12 of 250) in those having ERCP for other indications. This difference was statistically significant (P less than 0.05). However, pancreas divisum was not the sole risk factor for pancreatitis in the majority of our patients; most also had one of the commonly recognized causes for their pancreatitis. There is dispute about the indications for surgery in patients with recurrent acute pancreatitis and pancreas divisum, but without any other risk factor. We have reviewed the results of operations on 13 patients with pancreas divisum (Group B) treated in four different hospitals. Surgical sphincteroplasty was carried out on 10 patients with documented pancreatitis and seven of these had good results. Three patients who had operations for pain without documented pancreatitis were not improved. PMID- 2241653 TI - Adult donor kidney transplantation in small children: a surgical technique. PMID- 2241652 TI - Surgical knowledge base augmentation by medical rotations: does it happen? AB - A study of 4 groups of fifth year medical students taking Surgery during the 4 terms of 1989 at the University of Queensland was undertaken to determine whether there was assimilation of factual material relevant to the surgical knowledge base from the other specialty rotations done during the same year of the course. The records of multiple choice question (MCQ) examination results for the 210 students were retrieved and reviewed. The performance of the same students during their fourth-year rotation in Surgery was checked to make sure that the 4 groups did not already display unusual surgical aptitude or incompetence. The questions were categorized in order to ascertain that the content of all the examinations was similar. The results of students doing Surgery during the first of the 4 terms in 1989 were compared with subsequent groups. The difference between the groups was that those in the first term had not had the benefit of fifth year rotations through Internal Medicine, Psychiatry, General Practice and electives. Subsequent groups had increasing experience in the other specialties. The fourth and final group in the year had undertaken all four of the other rotations before doing Surgery. Significant improvement was found in the performance of each of the subsequent groups of students compared with the first-term group. This implies that there is an escalating accural of factual knowledge related to surgery from the fifth-year courses in Internal Medicine, Child Health and Psychiatry. PMID- 2241654 TI - Endoscopic management of intragastric migration of an Angelchik prosthesis. AB - The Angelchik prosthesis was devised as a simple surgical solution for reflux oesophagitis. Since 1983 there have been increasing reports of complications attributed to the prosthesis, the more serious being transmural erosion through the oesophageal or gastric wall. The majority of these have required repeat surgery, which is not without risks. A case report of an Angelchik prosthesis incompletely eroding into the stomach is presented. The prosthesis was tethered by a 1 cm-thick mucosal bridge which precluded simple extraction. Using an endoscopic sphincterotome, the bridge was divided and the prosthesis removed. Endoscopic methods of extracting intragastric Angelchik prostheses should be considered before surgery is undertaken for this complication. PMID- 2241655 TI - Carcinosarcoma: a rare tumour of the breast. AB - This report presents a case of carcinosarcoma, a rare tumour of the breast. The clinical and histological features and management are discussed. PMID- 2241656 TI - Treatment of recurrent desmoid tumour with tamoxifen. AB - A 30 year old woman with aggressive fibromatosis (desmoid) of the left upper arm and scapular region was treated with wide excision. Two years later she presented with extensive local recurrence of the scapular and deltoid regions. She was treated with tamoxifen (20 mg daily) and, over the next 6 months, the tumour regressed. She has been recurrence-free for the past year. We suggest that, in patients with desmoid tumours, hormone receptor determination and hormone therapy be attempted before subjecting patients to any form of radical treatment with surgery, radiotherapy or chemotherapy. PMID- 2241658 TI - Australia's Radiation Protection Standards (1989) PMID- 2241657 TI - Successive dislocations of a total hip arthroplasty complicated by acrylic cement interposition. AB - A case of two successive dislocations of a total hip arthroplasty in a single patient, complicated by acrylic cement interposition, is reported. Open reduction and removal of the cement was necessary in each case. This illustrates the importance of removing all cement debris at the time of prosthesis implantation. PMID- 2241659 TI - Computed tomographic assessment of coronary artery bypass grafts with fast dynamic scanning. AB - 28 coronary grafts in 12 symptomatic patients were studied at the time of graft angiography at Prince Charles Hospital. The grafts were studied using the Toshiba 900S scanner with bolus injections of contrast agent into an anticubital vein. The assessment was carried out using fast incremental and continuous acquisition scanning with stepped reconstructions in the last 5 patients. Of the 27 grafts, 16 were shown at angiography to be patent and of good calibre. 14 of these were similarly assessed at CT. 11 were either diseased or blocked at angiography, and these were graded also as small, stenosed or blocked at CT. This early study would support previous reports that CT does offer a reliable method of diagnosing good patent grafts. The study also suggests that with conventional fast dynamic scanning some information regarding graft quality can be obtained. PMID- 2241660 TI - The "Carpentier" thoracic aortic by-pass technique for management of descending aortic aneurysms and dissections--a radiological perspective. AB - The "Carpentier" thoracic aortic bypass procedure is a recently described and, until now, little used surgical technique for the treatment of descending thoracic aortic aneurysms and dissections. It involves the placement of a large conduit from the ascending aorta to the distal abdominal aorta through a midline sternotomy incision extended to the umbilicus and the subsequent interruption of the aorta just distal to the left subclavian artery via a left postero-lateral thoracotomy. As radiologists we should be aware of this alternative surgical option so that, in addition to diagnosing and classifying these aneurysms and dissections, we can assist our surgical colleagues in:-- a. The pre-operative assessment of the aorta for bypass grafting including the distal abdominal aorta b. The post-operative monitoring of the anticipated thrombotic occlusion of the descending thoracic aorta to the coeliac axis. PMID- 2241662 TI - Magnetic resonance imaging in herpes simplex encephalitis. AB - Four patients with clinical and serologically proven Herpes Simplex Encephalitis (HSE) were examined by Magnetic Resonance Imaging (MRI) following Computed Tomographic (CT) scans. MRI proved more sensitive at detecting the temporal lobe abnormalities than CT and invariably showed the lesions to be more extensive than suspected. The findings were consistent with an acute inflammatory process. Haemorrhage was present in only one patient. The sharp transition to normal at the lentiform nucleus previously described on CT was present in only one of the four patients, but was observed in a different patient with cerebral lymphoma and no evidence of HSE and is thus concluded to be less specific than previously thought. A repeat MRI scan at seven months on one of the patients showed persisting increased signal on T2 weighted images after resolution of the mass effect. The pathology and suspected mechanisms for the MRI appearances are discussed. MRI is concluded to be a valuable tool in the early diagnosis of HSE and in the longer term for further evaluation of residual disabilities. PMID- 2241661 TI - Radiologically controlled drainage of pleural and pulmonary collections. AB - Radiologically controlled catheter drainage is now accepted therapy for fluid collections in many parts of the body. While this is performed mainly in the abdomen, the chest is increasingly being drained percutaneously as an alternative to surgical drainage (van Sonnenberg et al 1984; Westcott 1985; O'Moore et al 1987; Crouch et al 1987). This report outlines the experience with 31 chest collections treated by the intervention radiologist over a two-year period. PMID- 2241663 TI - Holoprosencephaly (a case report). AB - We describe here a rare entity of Holoprosencephaly. The embryogenesis and the diagnostic aspects of this condition are highlighted. PMID- 2241664 TI - Characteristic appearances of colonic lipomas on barium enema: a guide to conservative management. AB - The double contrast barium enema appearances of seven colonic lipomas are reviewed. These lesions have submucosal features: intact mucosa, sharp margination and obtuse angles between the lesion and the adjacent colonic wall, as well as features characteristic of lipomas: pliability and shape change, broad pedicles and spherical appearances en face. They can be differentiated from the more significant colonic adenomas and then CT scanned to establish a histological diagnosis. The need for colonoscopic or surgical excision of these predominantly asymptomatic lesions occurring in elderly patients can be considerably reduced. PMID- 2241666 TI - Primary sacral bone tumours in children (report of 16 cases with a short literature review). AB - 16 cases of primary sacral bone tumours in children are reported. These include 13 patients with Ewing's sarcoma and 3 with very rare primary sacral bone tumours in childhood--chordoma, haemangiopericytoma and osteoblastoma. All sacral bone tumours, with the exception of Ewing's sarcoma are very rare in childhood. The possibility of a sacral tumour should be considered in a child with radiculopathy. CT and MR make the diagnosis of primary sacral bone tumours much easier with the added possibility of recognition of the true nature of the lesion in many instances. Reports of primary sacral bone tumours in children are scarce. Most of the patients are incorporated in adult series which do not specify the age of the child and the site of the tumour. The purpose of this paper is to describe 16 children with primary sacral bone tumours. PMID- 2241665 TI - Low dose intravenous urography: results and technique modifications. AB - 100 consecutive patients routinely referred for intravenous urography were examined using low doses of the low osmolar contrast medium Iohexol (Omnipaque 350mgl/ml). Their dosage schedule was based on the physiological parameters of age, sex, body weight and renal function. Comparison with a control group using standard contrast doses revealed a 42% reduction in contrast could be used, and still produce diagnostic studies. Nephrographic quality was reduced in the low dose group requiring technique modification, in particular a delayed film sequence. Further reductions in contrast use are envisaged in patients over the age of 40 years. PMID- 2241667 TI - Malignant psoas syndrome: recognition of an oncologic entity. AB - From January 1985 to January 1989 four patients with advanced cancer developed a syndrome characterized by proximal lumbosacral plexopathy and painful flexion of the ipsilateral hip with positive psoas muscle stretch test. Malignant involvement of the psoas major muscle was confirmed radiologically in all cases. Pain was intractable in 3 patients until time of death. We have termed this presentation the malignant psoas syndrome (MPS) and retrospective review of 427 oncology patients with "high risk" solid cancer culled no additional cases during the same 4-year period. We believe MPS to be a hitherto unreported complication of systemic cancer in which malignant involvement of the psoas muscle, in addition to producing severe nociceptive pain, contributes to the process of lumbosacral deafferentation. The clinical presentation, diagnosis and strategies of management of MPS are discussed. PMID- 2241668 TI - Percutaneous therapy for hepatic cysts. Case report and review of literature. PMID- 2241669 TI - Mesenteric giant lymph node hyperplasia--report of a case and review of the literature. AB - A case of hyaline vascular type of mesenteric giant lymph node hyperplasia (MGLNH) is presented. 15 previously reported cases were found in the literature with 14 belonging to the plasma cell type and one belonging to the hyaline vascular type. This is contrary to thoracic giant lymph node hyperplasia (TGLNH) where hyaline vascular type predominates. Like TGLNH, the hyaline vascular type of MGLNH produces no systemic symptoms but the plasma cell type is associated with various systemic symptoms and abnormal laboratory findings. PMID- 2241670 TI - Non fatal barium intravasation during barium enema. PMID- 2241671 TI - Free intra-peritoneal gas--an unusual aetiology. AB - The presence of free gas under one or both hemidiaphragms on an erect chest x-ray is most frequently the result of recent abdominal surgery or, in the absence of such surgery, is almost always indicative of a perforated abdominal viscus. A case is reported of a patient in whom pneumoperitoneum was discovered incidentally on a chest x-ray following extensive pelvic manipulation for acute inversion of the uterus. PMID- 2241672 TI - Sonographic recognition of pneumatosis intestinalis and portal gas in an 11 months-old infant--case report. AB - Sonography was performed on an 11-month old infant who presented with intestinal obstruction. Pneumatosis intestinalis and portal venous gas were detected in addition to dilated small bowel loops. Preoperative diagnosis of small bowel gangrene was made which was proven at operation. PMID- 2241673 TI - CT demonstration of traumatic ventral hernia and diaphragmatic rupture. A case report. AB - Traumatic ventral hernias occur rarely. A case is presented where bowel has herniated through a traumatic defect of the anterior abdominal musculature, demonstrated by CT. This has not been previously reported in the literature. These loops of bowel showed mural thickening and high density indicating severe injury and were found at laparotomy to be ischaemic. The patient simultaneously suffered rupture of the right hemidiaphragm, also demonstrated by CT and also an uncommon injury. PMID- 2241674 TI - Subclavian artery aneurysm presenting with recurrent haemoptysis--a case report. PMID- 2241675 TI - Paget's disease of the thoracic spine. A case report. AB - A case of cord compression, secondary to Paget's disease, and responding to medical therapy is presented. The role of current imaging techniques in this condition is discussed. PMID- 2241676 TI - Melorheostosis of the toe: a case report. AB - A case of melorheostosis in a 57-year-old Japanese woman is presented. This case is noteworthy because of its unusual radiographic features and local findings and its unusually long follow-up period of more than 29 years. Melorheostosis progresses very slowly over a long period of time, and can show bizarre features, simulating malignant tumor. PMID- 2241677 TI - History of avian medicine in the United States. X. Control of coccidiosis. PMID- 2241678 TI - Virulence factors of avian Escherichia coli. AB - A total of 45 strains of Escherichia coli isolates from chickens with colisepticemia were examined for virulence factors commonly found in pathogenic groups of E. coli. These strains were studied for the following: pathogenicity in 1-day-old chicks; toxin, hemolysin, and colicin production; cell invasiveness and adherence; hemagglutination for fimbriae detection; serum resistance; aerobactin production in iron-limited conditions; and plasmid content. The characteristics exhibited by virulent strains were invasion for HeLa and chicken fibroblast cells, serum resistance, colicin V, and aerobactin production. None of the isolates were toxigenic or positive in hemagglutination tests. The molecular genetic studies of the virulence factors by agarose electrophoresis showed that the plasmids of these strains are of high molecular weight. PMID- 2241679 TI - Comparison of enzyme-linked immunosorbent assay with dot immunobinding assay for detection of antibodies against Pasteurella multocida in turkeys. AB - A dot immunobinding assay (DIA) was developed to detect antibodies against Pasteurella multocida in turkey serum. Five coating antigens, namely, whole-cell (WC) antigen, sonicated cell lysate (SCL), crude capsular extract (CE), formalin extract (FE), and heat-stable antigen (HSA), were compared by enzyme-linked immunosorbent assay (ELISA) and DIA using reference antisera against P. multocida organisms. WC and SCL antigens showed higher sensitivity, whereas FE and HSA antigens were more specific coating antigens in both assays. The specificity of DIA was greater than ELISA by comparing the P/N ratios of HSA against serum prepared from heterologous serotype of P. multocida. The DIA had also several distinct advantages over the ELISA, which included reduction of the manipulation time and more uniform binding of coating antigens onto the nitrocellulose membranes compared with binding of coating antigens to microtiter plates for ELISA. PMID- 2241680 TI - Pathogenesis of Salmonella enteritidis infection in laying chickens. I. Studies on egg transmission, clinical signs, fecal shedding, and serologic responses. AB - Laying hens were inoculated orally, intracloacally (IC), or intravenously (IV) with Salmonella enteritidis phage type 8 isolates from a human (E700-87) eggs (Y 8P2), or the ovary of a hen (27A). Oral or IV inoculation of 2 x 10(8) to 4 x 10(8) colony-forming units (CFU) of E700-87 caused depression, anorexia, reduced egg production, diarrhea, and some mortality. Lower doses resulted in milder clinical signs. S. enteritidis was cultured from the shells of a few eggs but not from egg contents. Fecal shedding persisted for up to 6 weeks in some birds. Isolate Y-8P2 (10(6) CFU) also caused anorexia, diarrhea, and a drop in egg production. Hens inoculated orally or IC were less severely affected than those inoculated IV. Fecal shedding was intermittent and lasted up to 18 days. Eggshells from the IC-inoculated birds had the highest rate of contamination, and S. enteritidis was isolated from the albumen of 11 and yolk of three of 726 eggs. Oral inoculation of 10(6) CFU of isolate 27A resulted in a bacteremic infection with seeding of the liver, spleen, peritoneum, ovule, and oviduct. However, the birds remained clinically normal with normal egg production. S. enteritidis was cultured from the yolk and albumen of a small number of eggs until 11 days postinfection. Antigen prepared from S. enteritidis detected antibody in more sera than did commercially available S. pullorum antigen in agglutination tests. PMID- 2241681 TI - Possibilities of bacteremia and toxemia in death of chickens infected with Eimeria tenella. AB - The possibility that bacteremia and toxemia were the causes of death in cases of cecal coccidiosis was investigated. Germ-free and ordinary chickens with microflora were inoculated with sporulated oocysts of Eimeria tenella. At 5 days postinoculation, cecal lesions in ordinary chickens were more severe than those in germ-free ones. Cardiac blood, spleen, and liver were examined in ordinary chickens for bacteremia and endotoxemia, and small numbers of bacteria were recovered from both infected and uninfected birds. Endotoxin levels in plasma of E. tenella-infected birds were low and not different from the levels of uninfected controls. To examine unknown toxic factors, a large volume of serum from infected chickens was injected intravenously into uninfected birds. No significant clinical signs were observed. It is concluded that the intestinal bacteria increase the severity of coccidial lesions without bacteremia and toxemia. PMID- 2241682 TI - Toxicity of dietary monensin in quail. AB - Quail were fed monensin to determine liver damage, as measured by changes in activities of serum enzymes and liver microsomal enzymes. Monensin fed at a therapeutic level of 110 ppm for 2 weeks produced an increase in cytochrome P-450 and cytochrome b5 and induction of the activities of benzphetamine N-demethylase, aminopyrine N-demethylase, and aniline hydroxylase, with no changes in the activities of serum sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). On the other hand, quail fed 110 ppm, 220 ppm, and 330 ppm monensin in feed for 6 weeks showed a significant rise in SDH and AST activities at 330 ppm but not at 110 ppm and 220 ppm. The manifestations of liver toxicity observed at 330 ppm were accompanied by a significant decrease in all the aforementioned hepatic microsomal mixed-function oxidases. In contrast, quail fed monensin at 110 ppm and 220 ppm for 6 weeks produced no change in these parameters except for benzphetamine N-demethylase, aminopyrine N demethylase, and aniline hydroxylase, which were significantly increased in birds fed 220 ppm of monensin. PMID- 2241683 TI - Evaluation of sodium dodecyl sulfate-polyacrylamide gel electrophoresis purified proteins of Mycoplasma gallisepticum and M. synoviae as antigens in a dot-enzyme linked immunosorbent assay. AB - Selected immunogenic proteins of Mycoplasma gallisepticum (MG) strain R and M. synoviae (MS) isolate F10-2AS were purified from sodium dodecyl sulfate polyacrylamide gels. Purified MG proteins of 65 to 63 (p64) kilodaltons (kDa), and 26 and 24 (p26/24) kDa, and purified MS proteins of 53 (p53) kDa, 41 (p41) kDa, and 22 (p22) kDa were evaluated as potential antigens for an enzyme-linked immunosorbent assay (ELISA). Chicken antisera to MG, MS, or oil-emulsion vaccines were used to evaluate these purified proteins as antigens in a dot-ELISA. MG antigen p64 detected antibodies 3 days after the serum plate agglutination (SPA) test and 7 days before the hemagglutination-inhibition (HI) test. Antigen p64 detected antibodies to 12 MG isolates, and in sera from field outbreaks of MG. No cross-reactions with MS-positive antisera were seen with antigen p64. MG antigen p26/24 did not perform as well as p64. MS antigen p41 detected antibodies 5 days after the SPA test and at least 11 days before the HI test, and in sera from field outbreaks of MS. However, some MG-positive antisera reacted with p41. MS antigens p53 and p22 did not perform well. PMID- 2241684 TI - The relationship between the hemagglutination-inhibition test and the enzyme linked immunosorbent assay for the detection of antibody to Newcastle disease. AB - An assay of 364 chicken serum samples for Newcastle disease virus antibodies determined that a commercial NDV enzyme-linked immunosorbent assay (ELISA) had a 98.2% sensitivity and a 91.7% specificity relative to the NDV HI test. The ELISA values regressed significantly (F = 930, df = 1/362, P less than 0.001) on the hemagglutination-inhibition (HI) titers. The correlational coefficient was 0.85. For individuals, two tests can have the same result based upon chance alone. Kappa is a measure of agreement between two tests that corrects for this chance agreement. The kappa between the ELISA and HI test was calculated to be 0.84 (Z = 7.74, P = 0.00001), which indicates a highly significant agreement between the two tests. PMID- 2241685 TI - Influence of Campylobacter jejuni cecal colonization on immunoglobulin response in chickens. AB - The immunoglobulin response of chickens to colonization by Campylobacter jejuni isolates B-540 and Clin-1 was monitored. Chicken humoral IgG and biliary secretory IgA (sIgA) responses were assessed by enzyme-linked immunosorbent assay (ELISA). Samples were taken from 128 C. jejuni-colonized chickens and 104 uncolonized chickens housed in a controlled environment. An indirect ELISA was performed using the homologous isolate of C. jejuni as the capture antigen and was developed with the specific goat anti-chicken IgG or IgA alkaline phosphatase conjugates. The ELISA absorbance values of the test samples at 405 nm (serum diluted 1:32 and bile diluted 1:10) were normalized in direct proportion to standard sera and bile sample values. In the colonized chickens, humoral IgG activities were highest at hatch, dropped to their lowest level after 2 weeks, and increased by 8 weeks to levels similar to those detected at hatch. The sIgA activity was lowest at hatch and increased by 4 weeks in colonized chickens while remaining lower in the control chickens. Chickens colonized with isolate B-540 showed a primary sIgA response during the first 4 weeks and reached a plateau over the final 4 weeks. In spite of these limited humoral and secretory immunoglobulin responses, once the chicken ceca was colonized by C. jejuni, the organism persisted throughout the 8-week experiment. PMID- 2241686 TI - Influence of antibody treatment of Campylobacter jejuni on the dose required to colonize chicks. AB - This study was designed to clarify the role of antibodies in controlling chicken colonization by Campylobacter jejuni. Cecal colonization by C. jejuni was compared after the organism was exposed either to phosphate-buffered saline, normal rabbit serum, rabbit hyperimmune anti-C. jejuni serum, or anti-C. jejuni antibodies extracted from chicken bile. Antibodies from chicken bile were extracted by affinity absorption against outer-membrane proteins from the challenge organism. Sera were heated 1 hour at 56 C to destroy complement activity. Bacterial inoculum levels were enumerated after 1 hour exposure at 4 C to the various treatments. The heated sera and the bile antibodies were not bactericidal, and bacterial agglutination was not evident. Serial dilutions of the antibody-treated C. jejuni were given by gavage into 1-day-old chicks. Six days later, the ceca were removed from the chicks, and samples were cultured on Campylobacter-charcoal differential agar. The colonization dose-50% was increased by twofold to 160-fold when the organism was preincubated with hyperimmune antiserum or the bile antibodies as compared with preincubation with phosphate buffered saline. We conclude that antibodies inhibit chicken cecal colonization by C. jejuni. PMID- 2241688 TI - Factors affecting the development of respiratory disease complex in chickens. AB - Factors playing a part in the development of respiratory disease complex in chickens were investigated in a series of experiments. The experimental infection was produced by exposing chickens to Mycoplasma gallisepticum and the B1 vaccine strain of Newcastle disease virus and later exposing them to aerosols containing the O1:K1 serotype of Escherichia coli. Chickens became susceptible (pericarditis or death) to E. coli 8 days after mixed respiratory disease challenge. One day after respiratory disease challenge, lesions consisted of edema and infiltration with lymphoid cells and heterophils. At the time of susceptibility to E. coli, the lesions were strongly lymphoid with many dense follicular areas and very few heterophils. The incidence of pericarditis and death was similar when the concentration of bacteria in the aerosol inoculum ranged between 10(9)/ml and 10(5)/ml. At the time of maximum susceptibility to aerosol challenge, chickens were less susceptible to intravenously administered E. coli than were the uninfected controls. Resistance of chickens that had been selectively bred for a high (HA) or low (LA) antibody response to sheep erythrocytes was compared. HA chickens were more resistant to respiratory agents and less resistant to E. coli than LA line chickens. When the lines were exposed to respiratory disease followed by exposure to aerosols containing E. coli, the HA line had the lowest incidence of pericarditis and death. PMID- 2241687 TI - Influence of host lineage on cecal colonization by Campylobacter jejuni in chickens. AB - The resistance to cecal colonization by Campylobacter jejuni was assessed by challenging three crossbred stocks of commercially available broiler chickens. These three stocks, designated A, B, and C, were related as follows: Offspring from four pedigreed grandparent flocks were used as progenitors. Stock B was derived by cross-breeding grandparent 1 with grandparent 3. Stocks A and C were crossbreeds from grandparents 1 and 2 and grandparents 3 and 4, respectively. Campylobacter jejuni were gavaged into 48-hour-old chicks, using the same levels of challenge dose for each of the different chicken stocks. Six days post challenge, the birds were sacrificed, and cecal contents were plated onto Campylobacter-selective media. Results from two replicate trials with three isolates of C. jejuni indicated that chicken stock A was colonized in only two of 60 ceca, stock B in six of 60, and stock C in 19 of 60 chicken ceca. Statistical analysis of these data indicate that resistance to cecal colonization by C. jejuni was significantly (P less than 0.05) influenced through chicken host lineage. PMID- 2241689 TI - Restriction endonuclease analysis of Mycoplasma synoviae strains. AB - A diverse group of Mycoplasma synoviae strains from various hosts, pathological processes, and geographic areas collected over about 25 years were analyzed by restriction endonuclease analysis. The results suggest that restriction endonuclease analysis of M. synoviae strains may be a useful strain identification tool to study epidemiological problems. PMID- 2241691 TI - Biological control of Salmonella typhimurium in young chickens. AB - The effect of dietary lactose and anaerobic cultures of cecal microflora of mature chickens on the colonization of young broiler chickens by Salmonella typhimurium was evaluated. Newly hatched chicks were given either no treatment (controls), anaerobic cecal cultures, lactose (2.5%) in the drinking water, or both anaerobic cultures and lactose. Chicks were challenged per os at 3 days of age with either 10(6) or 10(8) S. typhimurium resistant to nalidixic acid and novobiocin. On day 10, the cecal contents of the chicks were examined for S. typhimurium, pH, short-chained volatile fatty acids (VFAs), undissociated VFAs, and lactic acid. Chicks given either lactose alone or cecal anaerobes alone had significantly (P less than 0.05) fewer S. typhimurium recovered from their ceca than the controls. Chicks given the combination of dietary lactose and cecal anaerobes had significantly fewer S. typhimurium recovered from their ceca than the chicks given dietary lactose or cecal anaerobes alone. Chicks given lactose had significant (P less than 0.05) increases in the lactic acid concentration of their cecal contents. Increased lactic acid concentrations were directly correlated to decreased cecal pH values and caused a reduction in the total concentration of VFAs but a significant (P less than 0.05) increase in the undissociated form of some VFAs. PMID- 2241690 TI - Effect of dietary lactose on cecal pH, bacteriostatic volatile fatty acids, and Salmonella typhimurium colonization of broiler chicks. AB - One-day-old broiler chicks were inoculated with volatile fatty acid producing cecal flora from adult chickens. The chicks were divided into four groups and provided 1) no lactose, 2) 2.5% lactose in water, 3) 5% lactose in feed, or 4) 10% lactose in feed, until 10 days of age. All groups were challenged at 3 days of age with 10(6) or 10(8) S. typhimurium. At 10 days, the number of Salmonella in the ceca of the chicks challenged with 10(6) Salmonella was significantly decreased (P less than 0.01) in the groups provided lactose as compared with the controls. A significant decrease (P less than 0.01) in Salmonella numbers occurred in the chicks challenged with 10(8) Salmonella and provided 10% lactose. Providing 2.5% lactose or 5% lactose failed to inhibit Salmonella growth in chicks challenged with 10(8) Salmonella. The pH of the ceca of the groups provided lactose decreased significantly (P less than 0.05) and was accompanied by significant increases (P less than 0.01) in the concentrations of bacteriostatic acetic and propionic acids. Results showed that providing dietary lactose to broiler chicks and inoculation with normal cecal flora decreased cecal pH, increased the concentrations of bacteriostatic volatile fatty acids, and inhibited Salmonella colonization. PMID- 2241692 TI - Efficacy of maduramicin ammonium against coccidiosis in turkeys under laboratory and floor-pen conditions. AB - Experimental infections with field isolates of Eimeria meleagrimitis, E. adenoeides, E. gallopavonis, and E. dispersa in turkey poults were used to test the efficacy of maduramicin ammonium at 2.5-10 ppm in laboratory experiments. Infection with single or mixed species of coccidia reduced the weight gain of unmedicated infected controls and caused 18.1-65% mortality in two experiments. Maduramicin ammonium given at 5-7 ppm prevented mortality, significantly reduced droppings scores and oocyst passage, and improved weight gain to near that of the unmedicated uninfected controls. Maduramicin ammonium was tested at 4-7 ppm in a floor-pen trial lasting 10 weeks. Mortality from coccidiosis averaged 11.9% in unmedicated controls, compared with 0.6% with 4 ppm of maduramicin or no mortality with 5-7 ppm. Average weight gain and feed conversion at 10 weeks were significantly improved over unmedicated infected controls when maduramicin ammonium was given at 5-7 ppm. These results suggest that maduramicin ammonium is highly efficacious against field isolates of Eimeria in turkeys, especially within the range of 5-7 ppm in the feed. PMID- 2241693 TI - Evaluation of chicken heterophil adherence. AB - Adherence of chicken heterophils was evaluated at 37 C using preconstructed columns containing various weights of nylon fiber (75 mg, 100 mg, or 125 mg) and whole blood anticoagulated with sodium heparin or 10% disodium ethylenediamine tetraacetic acid (EDTA). Additionally, 50-mg and 75-mg nylon fiber columns incubated at 41 C were used to evaluate heterophil adherence at an increased temperature. The mean percent adherence for heparin-anticoagulated blood applied to 75-mg, 100-mg, and 125-mg nylon fiber columns at 37 C was 76%, 92% and 97.4%, respectively. Samples applied to 50-mg and 75-mg columns at 41 C had adherence values of 27% and 85%, respectively. When paired samples of blood anticoagulated with EDTA or heparin were evaluated, the EDTA samples had significantly decreased heterophil adherence (paired t-test). Results indicate that increased or decreased adherence of chicken heterophils would best be detected using 75-mg nylon fiber columns incubated 37 C and whole blood collected in sodium heparin. PMID- 2241694 TI - Serotyping of Haemophilus paragallinarum by the Page scheme: comparison of the use of agglutination and hemagglutination-inhibition tests. AB - Seventy-two isolates of Haemophilus paragallinarum were serotyped according to the Page scheme, using a new hemagglutination-inhibition (HI) test. The results were compared with the plate agglutination method conventionally used in the Page scheme. The HI test used washed cells of H. paragallinarum, glutaraldehyde-fixed chicken erythrocytes, and rabbit antisera originally produced for the agglutination method. For 49 of the isolates, there was complete correlation between the results of the HI serotyping test and the previously performed agglutination test--23 were serovar A, two were serovar B, and 24 were serovar C. The other 23 isolates were nontypable by the agglutination test, but 21 of them could be serotyped by the HI method--six as serovar A, two as serovar B, and 13 as serovar C. Nine isolates required treatment of the bacterial cells with hyaluronidase for the expression of hemagglutination (HA) activity. Two isolates did not have HA activity despite hyaluronidase treatment and so could not be serotyped by the HI test. PMID- 2241695 TI - Chlamydiosis in captive raptors. AB - Chlamydia psittaci was isolated from four red-tailed hawks (Buteo jamaicensis) that died suddenly and from seven birds that survived at a raptor rehabilitation center in California in 1983. One hundred captive raptors representing 14 species in five families were subsequently tested serologically and by direct cloacal culture. C. psittaci was isolated from seven clinically normal birds. Forty-four percent of the raptors were considered positive using an enzyme-linked immunosorbent assay (ELISA), and 19% were suspects. The ELISA was repeated on 54 raptors in 1986. Forty-one percent of the birds were considered positive, and 35% were suspect, indicating that C. psittaci is endemic in the population. PMID- 2241697 TI - Cystic testicular degeneration in furazolidone toxicosis of sexually immature ducks. AB - Cystic testicular tubular dilatation was seen in ducklings fed a ration containing furazolidone at 250, 400, 550, or 700 ppm for 28 days. Gross evidence of cystic testicular dilatation was observed at necropsy in 16% (32/203) of the ducklings that survived to the end of the study. Gross testicular lesions consisted of various degrees of enlargement with increased translucency in moderately to severely enlarged testicles. Histological evidence of cystic testicular dilatation was present in 45% (41/91) of the testicles examined. Histologically, the tubules were in various states of dilatation with attenuation of the seminiferous epithelium proportional to the severity of dilatation. In the most severely affected testicles, tubules were greatly dilated, distorted, and fluid-filled, with extensively flattened epithelium visible on the inner margin of the tubule as a thin rim of cytoplasm with a protuberant nucleus. Interstitial tissues were compressed to thin septa between the dilated tubules. PMID- 2241696 TI - Effect of dietary lactose on Salmonella colonization of market-age broiler chickens. AB - The effect of providing lactose in feed and inoculation with volatile fatty acid producing anaerobic cultures (AC) of cecal flora on Salmonella typhimurium colonization was evaluated in broilers. One-day-old chicks were divided into four groups and provided 1) no lactose, no AC; 2) AC, no lactose; 3) AC and lactose on days 1-10; or 4) AC and lactose on days 1-40. All groups were challenged per os with 10(6) Salmonella on day 3 and with 10(8) Salmonella on day 33. Salmonella growth in the cecal contents was significantly decreased (P less than 0.01) on day 10 in the chicks provided lactose from day 1-10. However, after the removal of lactose from the diet, the chicks were susceptible to Salmonella colonization. The number of Salmonella in the ceca was significantly reduced (P less than 0.05) in the chicks provided lactose throughout the 40-day growing period. Dietary lactose decreased the pH of the cecal contents and was accompanied by marked increases in the concentrations of undissociated bacteriostatic volatile fatty acids in the cecal contents. PMID- 2241698 TI - The relationship of Cryptosporidium sp. infection of the bursa of Fabricius, intestinal tract, and respiratory system of chickens in Georgia, 1974-1988. AB - During 1974-1984, cryptosporidiosis was diagnosed in slightly more than 1% (63/6050 = 1.04%) of histopathology reports on chickens and turkeys made at two Georgia diagnostic laboratories. During 1985-1988, cryptosporidiosis was diagnosed in almost 6% (157/2622 = 5.99%) of histopathology reports on chickens and turkeys made at the two laboratories. Intestinal and respiratory Cryptosporidium sp. infections have increased significantly (p less than 0.01) with time. During the same period, there was no statistical pattern for bursa of Fabricius Cryptosporidium sp. infections, and there was no relationship between the incidence of bursal infections and the incidence of either respiratory or intestinal infections. PMID- 2241699 TI - Recombinant DNA probes for Mycoplasma synoviae. AB - A genomic library was prepared from Mycoplasma synoviae (MS) strain WVU 1853 cloned in plasmid vector pUC8 and transformed in Escherichia coli host JM83. In dot blot assays, four transformed E. coli clones hybridized with 32P-labeled chromosomal DNA of MS but not with 32P-labeled chromosomal DNA of M. gallisepticum (MG) strain S6. In Southern hybridization, each of the CsCl purified recombinant plasmid clones was shown to contain two MS DNA fragments between 1.0 to 2.3 kbp in length. 32P-Labeled probes prepared from each of the four recombinant plasmids hybridized in dot blot assays with MS strain WVU 1853 and nine MS field isolates but not with MG strains S6, K810, F2F10, four MG field isolates, and 15 other species of avian mycoplasmas. PMID- 2241700 TI - Characterization of the toxicity of the mycotoxins aflatoxin, ochratoxin, and T-2 toxin in game birds. I. Chukar partridge. AB - Chukar partridges were fed diets containing 1.25, 2.5, or 5 ppm aflatoxin; 1, 2, or 4 ppm ochratoxin A (OA); or 4, 8, or 16 ppm T-2 toxin. Toxin-induced mortality was seen during the third week with 4 ppm OA (12.5%) and 16 ppm T-2 toxin (15%), compared with the mortality in control chukars fed no toxin (2.5%). Body weights were significantly decreased by the highest level of aflatoxin at 3 weeks of age, by the highest level of OA by 2 weeks of age, and by 8 and 16 ppm T-2 toxin by 1 week of age. Aflatoxin did not affect liver weight and OA did not increase kidney weight in 3-week-old chukars. There was a slight decrease in kidney weight in chukars fed 4 ppm OA; however, the decrease was related to the decrease in body weight produced by the toxin. Mouth lesions were seen at all levels of T-2 toxin fed. PMID- 2241701 TI - Chicken anemia agent: an electron microscopic study. AB - Particles of chicken anemia agent (CAA) negatively stained with uranyl acetate were found to be 26.5 nm in diameter. The surface detail evident on the particles indicated that the virus capsid was composed of 32 structural subunits arranged as in a class P = 3 icosahedron with a triangulation number of 3. Using mouse monoclonal antibodies to CAA and a gold-labeled goat anti-mouse IgG, CAA-specific structures were observed by thin-section electron microscopy in infected MDCC MSB1 cells and in thymic lymphocytes from experimentally infected chicks. These consisted of electron-dense, granular, non-membrane-bound nuclear inclusions, which were often ring-shaped, and cytoplasmic accumulations of microtubules. Aggregates of virus-like particles were sometimes observed in the nuclei of infected MDCC-MSB1 cells. The nucleolar involvement that is characteristic of the morphogenesis of parvoviruses was not observed with CAA. PMID- 2241702 TI - Intracloacal Salmonella typhimurium infection of broiler chickens: reduction of colonization with anaerobic organisms and dietary lactose. AB - The combined effect of treatments with dietary lactose plus anaerobic organisms on cecal colonization of broiler chicks by Salmonella typhimurium was evaluated. Chickens treated with a combination of anaerobic organisms and 7% dietary lactose were resistant to cecal colonization by S. typhimurium. The number of recoverable S. typhimurium cells per gram of cecal contents taken on days 10 and 15 after infection was significantly reduced. Treatment with anaerobes without the addition of lactose did not effectively control cecal colonization. Intracloacal inoculations with bacterial concentrations that varied by 10,000-fold resulted in roughly similar levels of colonization. The treatments resulted in reduced cecal pH and elevated levels of undissociated volatile fatty acids. Statistically significant correlations (P less than 0.01) were observed between the S. typhimurium concentrations in cecal material and the concentrations of undissociated fatty acids (r = -0.79, and between the bacterial counts and pH (r = 0.72). PMID- 2241703 TI - Use of a hypobaric chamber as a model system for investigating ascites in broilers. AB - In a series of experiments, broilers were reared at simulated altitudes of 3000, 3500, and 5000 meters utilizing a hypobaric chamber. The purpose was to evaluate the chamber as a model for ascites syndrome and to further study the pathophysiology of this disease. Results show that this model can effectively reproduce the disease as it is seen in the field. Birds reared at the simulated altitude of 5000 meters had a statistically significant increase in EKG amplitude, packed cell volume, and heart-to-body-weight and lung-to-body-weight ratios when compared with controls reared at 366 meters. Additionally, there was a trend for birds dying of ascites to have larger-amplitude EKGs than survivors when reared at 5000 meters. PMID- 2241704 TI - Effect of exposure to a short-duration sound on the stress response of chickens. AB - Chickens were subjected to the sound produced by banging on a metal pail (104 decibels) for 30 seconds. Heterophil/lymphocyte (H/L) ratios began to rise 18 hours later, reaching their maximum value (0.62) in 20 hours and returning to pre stress values after 30 hours. Neither resistance to Escherichia coli challenge infection nor antibody response were altered. PMID- 2241705 TI - An ectopic wing in a wild black vulture (Coragyps atratus). AB - An approximately 5-month-old black vulture (Coragyps atratus) was presented with the chief complaint of cervicomelia. A full-sized ectopic wing, with its own pectoral girdle, was found attached to the dorsal surface of the last few cervical vertebrae. There was deformation (right dorsolateral narrowing) of the spinal canal at the point of attachment with a corresponding compression of the spinal cord. PMID- 2241706 TI - Sudden death syndrome in turkey hens. AB - A turkey breeder flock of 5600 31-week-old hens experienced an abrupt increase in daily mortality for a 2-day period. This higher mortality rate corresponded with the handling and moving of the hens 1 to 2 days before. No clinical illness was seen in the hens before carcasses were discovered. The four hens that were necropsied had small spleens, congested lungs, and enlarged livers. The most consistent histologic lesions were pulmonary hemorrhage and edema, and congestion of veins and capillaries in several visceral organs. One hen had subserosal hemorrhage of the oviduct and perirenal hemorrhage. The increased mortality pattern, the lack of clinical signs, and the histopathologic changes are consistent with a diagnosis of sudden death syndrome. The presence of concurrent inflammatory lesions in the lungs predisposed the hens to sudden death following the stress of handling and moving. PMID- 2241707 TI - Squamous-cell carcinoma of the pharyngeal cavity in a Jersey black giant rooster. AB - Squamous-cell carcinoma of the pharyngeal cavity was diagnosed in a 3-year-old Jersey black giant male chicken. Grossly, the carcinoma was round with irregular edges, yellow-tan, cauliflower-like with a crusty surface, and attached to the roof and sides of the pharyngeal cavity. Histologically, the surface of the mass was covered by a dense mat of necrotic mucosa and inflammatory cells. A broad front of neoplastic cords consisting of squamous epithelial cells extended into the lamina propria. There was no evidence of vascular invasion or metastasis. PMID- 2241708 TI - Characterization of a gram-positive bacterium from the proventriculus of budgerigars (Melopsittacus undulatus). AB - The cellular, cultural, and biochemical characteristics of eight isolates of a large gram-positive bacillus that are commonly observed as apparently normal flora in the proventriculus of budgerigars (Melopsittacus undulatus) were determined. The bacterium was highly pleomorphic and changed markedly in both diameter and length when subcultured on agar media. The bacterium was facultative anaerobic and capnophilic, hemolytic on blood agar, and formed flat colonies with irregular edges after incubation for several days. All isolates grew on sodium azide agar but did not grow on MacConkey agar. The isolates were catalase negative and oxidase-negative and did not reduce nitrate. All isolates failed to utilize arginine, lysine, ornithine or tryptophane but produced acid from glucose, galactose, levulose, maltose, melibiose, starch, and sucrose. All isolates produced acetoin from glucose and hydrolyzed esculin. The eight isolates could not be identified to either genus or species level based on the descriptions of currently classified organisms in the division Firmicutes as described in Bergey's Manual of Systematic Bacteriology. PMID- 2241709 TI - Small intestinal cryptosporidiosis in cockatiels associated with Cryptosporidium baileyi-like oocysts. AB - Four of six cockatiels died within a week after being purchased from a commercial breeder. A fifth bird was euthanatized and necropsied during this time, and tissues were collected for microscopic examination. The small intestine had moderate numbers of Cryptosporidium sp. parasites present. A few large, basophilic intranuclear inclusions were present in renal ductular epithelium. Cryptosporidium sp. oocysts were found in the feces of the surviving bird. Thirty oocysts were 7.2 by 5.5 microns. The shape index was 1.31. Morphological examinations of the fecal oocysts indicated that the Cryptosporidium species infecting the cockatiels was similar to C. baileyi, a parasite that is not usually associated with small-intestinal infections. PMID- 2241710 TI - Factors that determine medical interest in psychiatry. PMID- 2241711 TI - Effects on care-givers of special day care programmes for dementia sufferers. PMID- 2241712 TI - Damages for self-inflicted injuries. PMID- 2241713 TI - Compulsive and impulsive sexual offences. PMID- 2241714 TI - Decidedly pointing to central mischief. PMID- 2241715 TI - Australasian field trials of the Mental and Behavioural Disorders section of the draft ICD-10. AB - Field trials of the "Mental and Behavioural Disorders" section of the 1987 draft of the ICD-10 have been co-ordinated for the World Health Organisation by a number of regional centres. The design of the field trials and the major features of ICD-10 are briefly discussed. The results of the field trial in the Western Pacific region are described, and compared with the results of the original DSM III field trials. ICD-10 appears to be an acceptably reliable diagnostic system, and the ratings of its feasibility and utility by participating clinicians suggest that it will be seen as a distinct advance over ICD-9. PMID- 2241716 TI - The prevalence of emotional and behaviour disorders and patterns of service utilisation in children and adolescents. AB - This study compared the prevalence of emotional and behavioural disorders in children attending schools of different socio-economic class. In addition, the study compared the rate of service utilization by children with and without disorders. Using cutoff scores recommended for use with Australian children, the prevalence of disorders in schools of different socio-economic class ranged from 2.3 +/- 2.2 to 13.9 +/- 5.3 per 100 children, with the highest prevalence being found in the lower socio-economic class schools. Although few children with disorders had been seen in a mental health clinic, advice had been sought from other services with regard to 66% of these children. This high rate of service utilization by children with disorders highlights the key role that general practitioners, school guidance officers and hospital services could play in facilitating the early identification and management of children with emotional and behavioural disorders. PMID- 2241718 TI - Treatment outlines for paranoid, schizotypal and schizoid personality disorders. The Quality Assurance Project. AB - Treatment outlines for paranoid, schizotypal and schizoid personality disorders were developed by having nominated experts consider their own views in the light of the treatment literature and the responses of practising psychiatrists. In the detailed recommendations it is clear that while patients with all three disorders often present for treatment in a crisis and often see no issue other than the resolution of the crisis, patients with schizoid personality disorder can use long-term psychotherapy to develop and change to the extent of no longer being handicapped. PMID- 2241717 TI - Child psychiatry in Hong Kong: an overview. AB - Hong Kong has a population of 5.5 million with 1.3 million below the age of 15. Child psychiatry has been very under-developed until recently. The brief history and development of child psychiatry in Hong Kong, and specifically that of the Child and Adolescent Psychiatric Unit at the Prince of Wales Hospital, the teaching hospital of The Chinese University of Hong Kong, are described. Traditionally psychiatric services for children in Hong Kong were heavily skewed towards neuropsychiatric and developmental conditions but in this Unit a full spectrum of child psychiatric conditions are seen. Relevant clinical statistics are used to illustrate these differences as well as to further highlight the philosophy and practice of the Unit. Other aspects, such as undergraduate and postgraduate teaching, and research are also mentioned. The magnitude of child psychiatric morbidity in Hong Kong is briefly illustrated with a three-stage epidemiological study done in a primary school in a lower middle social class area. It was found that 16.3% of the children were psychiatrically disturbed. Emotional disorder, with a prevalence of 8.8%, was the commonest condition. Finally, the future development of child psychiatry in Hong Kong is discussed, addressing the disconcerting facts of a huge population and very limited resources. PMID- 2241719 TI - Psychosocial effects on carers of living with persons with dementia. AB - A survey of members of the Alzheimer's Disease and Related Disorders Society confirmed high rates of psychological morbidity, though not of depression, and social isolation in family carers of persons with dementia. Psychological morbidity in carers was associated with having an affected person at home, the carer being a spouse, demanding problem behaviours, poor physical health in the carer, social isolation, dissatisfaction with social supports, greater use of psychotropic medication, and a deteriorated marital relationship. Carers and patients had high rates of consultations with doctors and other health professionals. There was a vulnerable group of carers who were impaired psychologically, socially and physically. The identification of risk factors to carer morbidity may lead to useful interventions. PMID- 2241721 TI - Health services research and the future of Australian psychiatry. PMID- 2241720 TI - A survey of dementia carers: doctors' communications, problem behaviours and institutional care. AB - A survey of carers belonging to the Alzheimer's Disease and Related Disorders Society (ADARDS) had three aims: (i) to investigate the process of health professionals providing information to patients and carers: (ii) to determine the nature of problems burdening carers; and (iii) to examine factors associated with institutional placement. Carers reported on deficiencies in the provision of information and indicated their preferences as to how the information should be given. ADARDS, general practitioners and other health professionals were reportedly helpful, with each appearing to have a role in providing information about dementia. Multiple problem behaviours were reported by most carers, especially difficulties with communication, the need for constant supervision and disruption to personal life. Institutional care was most highly correlated with dependency problems, severity of dementia and a non-spouse carer. Implications include the need for training of doctors in communication and education about dementia with particular attention to management of dependency problems. PMID- 2241723 TI - Australian suicide data and the use of "undetermined" death category (1968-1985). AB - There has been considerable recent debate about the impact that changes in the use of the "undetermined" death classification may have upon trends in national suicide statistics. This study focused on changes over time within each state in Australia in an attempt to determine the source of apparent patterns in national data. Considerable intra- and inter-state variability was revealed, and it was concluded that, apart from a general trend for decreasing use of the undetermined category, the data are not of sufficient quantity to warrant further interpretation. The suggestion that changes in classification practices by coroners may have contributed to the rise in young male suicides was not supported. PMID- 2241722 TI - Suicide from river bridges. AB - The opening of a new high river bridge in Brisbane allowed a naturalistic experimental testing of whether the sample engaging in suicidal behaviour from the new bridge was similar to that from the adjoining older bridge. Substantial differences were found for the two samples. This suggests that persons prevented from jumping from one bridge, for example by a barrier, will not automatically jump from the alternative bridge although a minority may do so. PMID- 2241724 TI - The power of mercy. AB - Throughout history heads of state have reserved for themselves the prerogative to exercise mercy and pardon not only for serious crimes but for lesser ones as well. The newly emerging state of Papua New Guinea is no exception. My experience as the psychiatrist member of the advisory committee on such executive clemency since its inception twelve years ago will be discussed. PMID- 2241725 TI - Can reliance be placed on a single meta-analysis? AB - Meta-analysis replaced statistical significance with effect size in the hope of resolving controversy concerning evaluation of treatment effects. Statistical significance measured reliability of the effect of treatment, not its efficacy. It was strongly influenced by the number of subjects investigated. Effect size as assessed originally, eliminated this influence but by standardizing the size of the treatment effect could distort it. Meta-analyses which combine the results of studies which employ different subject types, outcome measures, treatment aims, no-treatment rather than placebo controls or therapists with varying experience can be misleading. To ensure discussion of these variables meta-analyses should be used as an aid rather than a substitute for literature review. While meta analyses produce contradictory findings, it seems unwise to rely on the conclusions of an individual analysis. Their consistent finding that placebo treatments obtain markedly higher effect sizes than no treatment hopefully will render the use of untreated control groups obsolete. PMID- 2241727 TI - Community psychological effects following a non-fatal aircraft accident. AB - Following a non-fatal military aircraft accident, two of the authors interviewed the crewmen involved in the accident, their spouses, fellow squadron members and their spouses, and individuals from the fire crew and control tower on duty during the accident. A total of 37 respondents completed questionnaires which reported the presence of intrusive, avoidant, depressive/anxious, and post traumatic stress symptoms. Spouses reported more symptoms after the accident than their flying husbands. Intrusive symptoms were most common. Symptoms were correlated with various perceptions and experiences occurring prior to and following the accident. Several kinds of symptoms and experiences were significantly correlated with a perception of morale decline. This study suggests that even non-fatal aircraft accidents may have important psychological effects on those involved and on the surrounding community. Implications of these findings and recommendations for helping communities process traumatic events are discussed. PMID- 2241726 TI - Psychological consequences of spinal injury: a review of the literature. AB - The traumatic nature of spinal cord injury necessitates adjustments for the individual physically, socially, vocationally and sexually, as well as placing great strain on the family. Although one would suspect a high prevalence of psychological disruption following spinal cord injury, there is still much debate concerning the extent of the psychological reaction to such a trauma. This situation can partly be attributed to the lack of systematic research characteristic of most studies in this area. This paper reviews more recent literature which has investigated psychological morbidity in persons with spinal cord injury. The inadequacies of this research are discussed and suggestions for future research and psychological treatment for the spinal injured are provided. PMID- 2241728 TI - The heart rate spectrum in simulated flight: reproducibility and effects of atropine. AB - The heart rate spectrum (HRS) was computed on eight pilots during simulated flight. Although respiratory-coupled heart rate variability (i.e., that produced by vagal inputs to the heart) varied three-fold across volunteers, each individual volunteer's data were very stable on three test days (median coefficient of variation = 5.4%). Atropine rapidly reduced heart rate variability at the respiratory frequency to the noise level (i.e., 74% decrease from predrug levels). Although there was no significant difference in the reduction induced by a 2 mg or 4 mg dose, there was a tendency for variability at this component of the spectrum to return to normal faster following 2 mg injection than after 4 mg injection. By the morning after injection at either dose, heart rate variability at the respiration component of the HRS was back to normal--indicating complete washout of the drug. This study revealed no technical limitation to using the HRS in real life situations outside of the laboratory and suggests that the test can be used to test the efficacy of other treatments or manipulations that reduce vagal tone to the heart. PMID- 2241729 TI - Onset of behavioral effects in mice exposed to 10 Gy 60Co radiation. AB - The effects of 10 Gray (Gy) 60 Co radiation on social behavior, locomotor activity, and body weight were assessed in individually housed male Swiss-Webster mice. In Experiment 1, aggressive behavior was evaluated prior to irradiation and for 7 d postirradiation by placing an untreated intruder in the irradiated or sham-irradiated resident's home cage for 5 min. Offensive aggressive behavior was not affected significantly by radiation until day 7 postirradiation, when attack latency increased, the frequency and duration of fighting decreased, and the frequency of bites, lunges, and chases decreased. Untreated intruder mice paired with irradiated resident mice showed a decrease in the duration of defensive upright postures and a decrease in the frequency of defensive upright postures, squeaks, and escapes on day 7 postirradiation. In Experiment 2, locomotor activity and body weight were monitored for 7 d postirradiation. Body weight was decreased in irradiated mice beginning 4 d postirradiation. Locomotor activity was suppressed in irradiated animals 90 min after irradiation and remained depressed throughout the 7-d testing period. PMID- 2241730 TI - Instability of ocular torsion in zero gravity: possible implications for space motion sickness. AB - Inherent asymmetries of the gravity-sensitive otolith organs of the inner ear may be well-compensated in ordinary 1 G, but rendered unstable in novel gravitational states. Several aspects of ocular counterrolling and spontaneous eye torsion, reflexes governed by the otoliths, were examined during the hypo- and hypergravity in parabolic flight on the NASA KC-135 aircraft. Among the subjects were two astronauts, one who had suffered space motion sickness during his mission and one who had not. Using an observed separation of scores of torsional instability at 0 G as the criterion, we divided our 10 subjects into the 5 highest and 5 lowest scorers, reminiscent of the approximately 50% who do and the 50% who do not experience space motion sickness (SMS). The astronaut who had had SMS was in the high group; and the one who had not was in the low group. At 1.8 G, the groups defined at 0 G were significantly different in the instability measure. They were also significantly different at both 0 G and 1.8 G in another measure, that of torsional variability. There were no differences between the groups in amplitude of eye torsion in 0 G or 1.8 G. None of the tests were significantly different in 1 G. The results suggest that these tests of eye torsion on the KC-135 might differentiate those who would experience SMS from those who would not. Proof of this speculation awaits replication of the study using only astronaut subjects. PMID- 2241731 TI - Rigid gas-permeable contact lens wear during + Gz acceleration. AB - This study was designed to determine how well rigid gas-permeable contact lenses maintain position on the cornea under high G forces, and the effect on visual acuity. One hyperopic and five myopic subjects were fitted with lenses made from Pasifocon C material (specific gravity = 1.07). Two lens diameters (8.8-9.4 mm and 9.6-10.0 mm) were compared upon the myopic subjects for centering on the cornea. Visual acuity was measured at + 1 Gz (baseline), +3 Gz, +4 Gz, +6 Gz, and +8 Gz in the straight-ahead, lateral, and up-gaze positions from three acuity charts mounted in the gondola. All lenses, as estimated from the videotape, decentered down the z axis 2-3 mm at high + Gz. Visual acuity was reduced at the higher +Gz levels to similar measurements in most subjects for both the contact lens and spectacle control rides. No lens displaced from the cornea or dislodged from the eye during any of the 25 centrifuge runs. PMID- 2241732 TI - Thermogenesis and thermoregulatory function of iron-deficient women without anemia. AB - Physiological responses at 16 degrees C were studied in 11 women, age 28 +/- 2(mean +/- S.E.) years and 26 +/- 2% fat, after their body iron stores were depleted by diet (5.0 mg iron x 2,000 kcal-1 x d-1), phlebotomy and menstruation for about 80 d and were repleted by diet (13.7 mg iron x 2,000 kcal-1 x d-1) for about 100 d, including daily iron supplementation (50 mg of iron as ferrous sulfate) for the last 14 d of repletion. Iron depletion was characterized by a decline (p less than 0.05) in hemoglobin (12.0 +/- 0.2 g x dl-1), ferritin (5.5 +/- 0.5 ng x ml-1) and body iron balance (-9.1 +/- 2.6 mg x 6 d-1). Iron repletion, including supplementation, increased (p less than 0.05) hemoglobin (12.6 +/- 0.1 g x dl-1), ferritin (9.5 +/- 0.4 ng x ml-1) and iron balance (+67 +/- 6.7 mg x 6 d-1). Iron depletion reduced (p less than 0.05) metabolic heat production (49.6 +/- 1.1 vs 53.6 +/- 1.2 W x m-2) during acute cold exposure. The rates of cooling of the core and periphery were greater (p less than 0.05) during iron depletion than repletion. A shift in the lower core temperature threshold for shivering was paralleled by an earlier onset of shivering (p less than 0.05) in iron depletion indicating an adaptation in cold tolerance in an attempt to maintain core temperature. Iron depletion was associated with blunted post exposure increases in plasma thyroid hormone concentrations and greater (p less than 0.05) increases in plasma norepinephrine concentrations as compared to iron repletion. In a subsample of the women, no significant effect of calcium or ascorbic acid supplementation was found on responses to cold exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241733 TI - Modulation of cutaneous flexor responses induced in man by vibration-elicited proprioceptive or exteroceptive inputs. AB - The effects of muscle tendon or skin vibration on the early and late components of polyphasic cutaneous responses elicited in the flexor carpi radialis by electrical stimulation of the radial nerve at the wrist were studied in the human, with all muscles at rest. Both early and late flexor responses were enhanced by flexor vibration and depressed by extensor vibration; facilitation was accompanied by a reduction of latency. Furthermore, when an "antagonist vibration response" was present, inhibition of the flexor reflexes was replaced by a facilitation. Palm skin vibration depressed both components of the flexor reflex, while dorsal or "back-hand" skin vibration induced either a facilitation or an inhibition. In addition, back-hand vibration modified the location of the sensations evoked by electrical stimulation of the nerve. In all cases, vibratory stimulus attenuated the perceived intensity of the electrical stimulus. These observations indicate that proprioceptive or exteroceptive information can modulate the gain of the cutaneous reflex loops in a flexible way, under supraspinal control. These data also suggest a possible impairment of the protective withdrawal reflex under vibratory environmental conditions at rest and eventually in active muscles. PMID- 2241734 TI - The effect of +Gz offset rate on recovery from acceleration-induced loss of consciousness. AB - The incapacitation resulting from +Gz-induced loss of consciousness (G-LOC) depends on the magnitude of the ischemic/hypoxic insult to the central nervous system (CNS). This magnitude is defined by the rate of onset of the +Gz, the +Gz level, the length of time at +Gz, the offset rate, and individual tolerance to +Gz. Offset rates have rarely been emphasized or even reported in +Gz research. This study compared the incapacitation between two groups of asymptomatic men resulting from generally similar rapid onset (greater than 3G/s) +Gz exposures to induce G-LOC but with different +Gz offset rates. For one group (N = 90) of G-LOC exposures the offset rate was 0.97 G/s and for the other group (N = 17) the offset rate was 2.75 G/s. The incapacitation following G-LOC with slower offset resulted in an absolute incapacitation period of 10.47 +/- 3 s, a relative incapacitation of 14.40 +/- 10.05 s, and a total incapacitation period of 25.04 +/- 10.13 s. With the more rapid offset G-LOC exposures the absolute incapacitation was 7.59 (+/- 3.14)s, relative incapacitation 5.40 +/- 3.38 s, and the total incapacitation was 13.20 +/- 4.36 s. The rate of +Gz offset also affects the time following G-LOC before onset of myoclonic convulsions. Rapid offset G-LOC exposures had a shorter period from the onset of unconsciousness to the onset of convulsions as compared to slower offset rates. The convulsion period, however, remained essentially the same. The results strongly favor an ischemic/hypoxic mechanism for G-LOC. The results also document the importance of offset rates in determining the magnitude of the ischemic-hypoxic insult to the CNS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241735 TI - Cervical dystonia following exposure to high-G forces. AB - Injuries to the cervical region have been associated with high-G loads sustained during air combat maneuvering (ACM) in high performance fighter aircraft. The spectrum of injuries ranges from mild neck pain to musculoskeletal strain, injury to the nerve roots or spinal cord, and fracture of the cervical spine. A 36-year old fighter pilot with 2,800 h in tactical jet aircraft developed progressive cervical dystonia (spasmodic torticollis), following an ACM flight. The patient was successfully treated with local intramuscular injections of botulinum toxin into the affected cervical muscles, resulting in total relief of his spasmodic torticollis. The aeromedical considerations of this rare complication of exposure to G forces in high performance aircraft are discussed. PMID- 2241736 TI - Flight crews with upper respiratory tract infections: epidemiology and failure to seek aeromedical attention. AB - A voluntary questionnaire was used to determine the epidemiology of upper respiratory infections (URI), and whether aeromedical attention was sought. Questionnaires completed by 256 of 276 eligible flight crewmembers revealed that over half, 61.7% (158), reported having greater than or equal to 1 URI during a 6 month period, for a total of 272 URIs. No statistically significant associations, p greater than 0.05, were noted between the occurrence of URI and sex, age, pilot vs. enlisted, or smoking status. Subjects with children living at home with them were more likely to report having URIs than those with no children, p less than 0.10. Aeromedical attention was not sought in 55.5% (151/272) of the URI episodes. An Aeromedical Concern (AMC) was determined to occur in 69.5% (105/151) of these representing 38.6% (105/272) of all URIs. The most common reason for AMC was taking self-prescribed medications. AMCs were more frequent among enlisted personnel than officers (pilots), p less than 0.05. Possible reasons why AMCs may occur are discussed. In summary, URIs are common in aircrews, as is the failure to seek aeromedical attention. PMID- 2241737 TI - Military aviation: a contact lens review. AB - The military aviation communities have benefitted from the development of advanced electro-optical avionics systems. One drawback that has emerged is an increasing system incompatibility with traditional spectacle visual corrections. An alternative solution to the refractive error correction problem that some services have been investigating is that of contact lens wear. Since this much debated topic is currently of command interest, a general overview of contact lens issues is presented as a framework for future discussions. PMID- 2241738 TI - MYCIN and NEOMYCIN: two approaches to generating explanations in rule-based expert systems. AB - The prototypical rule-based expert system is MYCIN, a computer program developed in the 1970's to diagnose and recommend therapy for serious infections. MYCIN is able to explain its reasoning at any point in a consultation by listing the rules it has under consideration at that moment. However, when MYCIN's rules were used as the subject matter for a computerized infectious disease tutoring system, it became apparent that these rules contained implicit knowledge about how to perform diagnostic tasks and that this knowledge was inaccessible to the explanation system and, therefore, to students. This paper briefly describes NEOMYCIN, an expert system that makes this implicit knowledge explicit, and shows the effect that this reconfiguration of knowledge has on generating explanations. PMID- 2241739 TI - The history of aviation medicine in Argentina. AB - Ascents in balloons were first performed in Buenos Aires in 1855, and this activity was later regulated through the "Argentine Air Club," founded in 1908, whose Vice President, Jorge Newbery, subsequently became officially known as the "Founder of Argentine Aeronautics." Airplanes appeared and the first pilots' licenses were granted on June 17, 1910. Medical advice was given for such feats as crossing The Andes Cordillera in a balloon in 1915. Medical requirements for flying activities led to the creation of the Psychophysical Fitness Center in 1922, the first of its kind in Argentina and South America. There, selection and periodical check-ups were performed according to medical standards prepared by Agesilao Milano, M.D., the Founder of Aviation Medicine in Argentina. Sanitary aviation began in 1911, and was formally organized in 1940. The first paper in aviation medicine was published in 1924. Teaching and research in aviation medicine started in 1933, and continued after the creation of the National Institute of Aviation Medicine in 1945, taking as its basic objective the physical fitness qualification for all flying activities. The Institute has been recognized as a University Establishment and rules Argentine national policy in aviation medicine. PMID- 2241740 TI - Cases from the aerospace medicine residents' teaching file. Case #38. A navigator with nonischemic central retinal vein occlusion progressing to ischemic central retinal vein occlusion. AB - A case report of a young USAF navigator with nonischemic central retinal vein occlusion progressing to ischemic central retinal vein occlusion is presented. This young man was treated with hyperbaric oxygen therapy early in the course of his disease with complete resolution of his condition. Two years later his vision remained 20/17. This is the first known case of central retinal vein occlusion being treated with hyperbaric oxygen. PMID- 2241741 TI - Will world peace mean less PTSD? PMID- 2241742 TI - Effects of acute hypoxia on cardiopulmonary responses to head-down tilt. AB - Six male subjects were exposed on two separate occasions to simulated microgravity with 28 degrees head-down tilt (HD) for 1 h with baseline followed by recovery at + 17 degrees head-up. Pulmonary ventilation, gas exchange, spirometry, and central and cerebral blood flow characteristics were compared while breathing ambient air (PIO2 = 122 mm Hg) and reduced FIO2 equivalent to 14,828 ft (PIO2 = 81 mm Hg). With hypoxia (HY), the increased tidal volume served to attenuate the drop in arterial saturation by reducing deadspace ventilation. Arterial and mixed venous PO2 values, estimated from peripheral venous samples and cardiac output (CO), were both maintained during HD in HY. Mixed venous PO2 was elevated by an increase in CO associated with a reduction in systemic resistance. Changes in spirometric indices during HD were not accentuated by HY, making the presence of interstitial edema unlikely. Cerebral flow and resistance showed minor reductions with HD. Tissue oxygenation and cardiopulmonary function were not notably effected by HD during HY, but a combination of these two stressors may predispose subjects to subsequent orthostatic intolerance during initial recovery. PMID- 2241743 TI - Thermal status of Antarctic divers. AB - I studied 5 wet-suited scuba divers studied on 26 dives in the Antarctic. The median duration of dives was 29 min, during which divers were usually involved in sampling or observations for marine biology or chemistry projects. Rectal temperature (Tre) and seven skin site temperatures were measured with thermistors, and mean skin temperature (Tsk) and heat loss estimated. Divers usually heated up during changing and transport to a dive. By the end of immersion, Tsk decreased to a median of 22 degrees C, and finger temperature decreased to a median of 10 degrees C, while the median heat loss during immersion was 850 kJ. Tre below 36 degrees C was not recorded. This study shows that divers do not become clinically hypothermic, but that they are subject to severe cooling, and skin temperatures reach levels at which manual and mental impairment may occur. PMID- 2241744 TI - Anti-LPS antibodies reduce endotoxemia in whole body 60Co irradiated primates: a preliminary report. AB - Long periods in space may expose astronauts to the potentially harmful effects of ionizing radiation. We have used a primate model to evaluate any role of lipopolysaccharide (LPS, endotoxin) in radiation sickness. Vervet monkeys, which had been whole-body 60Co irradiated with an LD100 exposure, had periodic blood samples taken for the determination of LPS, anti-LPS IgG antibodies and bacteriological studies. On day 2 post-irradiation, primates were treated i.m. with either sterile 0.9% saline, or equine anti-LPS hyperimmune plasma (Anti LPS), or orally with tripotassium-dicitrato-bismuthate ("Denol"). Gram positive bacteria were evident in blood samples of all animals as early as 2 d post irradiation. Gram negative bacteria were found in the blood of saline- and Denol treated primates by days 5 and 8, respectively, but first appeared on day 13 in the anti-LPS-treated animals. The saline controls and Denol-treated animals showed insignificant rises in plasma LPS on day 3, which increased further thereafter achieving significance on day 8 (p less than 0.01). These elevated levels persisted until death. However, in anti-LPS-treated monkeys, LPS concentrations remained below baseline until day 9, after which they rose significantly until death, but, were significantly less than the concentrations in both other groups (p less than 0.001). The anti-LPS-treated animals survived significantly longer than both the other groups (p less than 0.005). Since LPS may cause nausea, vomiting, diarrhea, anorexia and headaches, Anti-LPS administration may be of value in reducing plasma LPS concentration in humans and improving their performance and survivability. PMID- 2241745 TI - The susceptibility of rhesus monkeys to motion sickness. AB - The susceptibility of rhesus monkeys to motion sickness was investigated using test conditions that are provocative for eliciting motion sickness in squirrel monkeys. Ten male rhesus monkeys and ten male Bolivian squirrel monkeys were rotated in the vertical axis at 150 degrees/s for a maximum duration of 45 min. Each animal was tested in two conditions, continuous rotation and intermittent rotation. None of the rhesus monkeys vomited during the motion tests but all of the squirrel monkeys did. Differences were observed between the species in the amount of activity that occurred during motion tests, with the squirrel monkeys being significantly more active than the rhesus monkeys. These results, while substantiating anecdotal reports of the resistance of rhesus monkeys to motion sickness, should be interpreted with caution because of the documented differences that exist between various species with regard to stimuli that are provocative for eliciting motion sickness. PMID- 2241746 TI - Intraocular pressure, retinal vascular, and visual acuity changes during 48 hours of 10 degrees head-down tilt. AB - Intraocular pressures, retinal vascular diameters, and visual acuities of nine men (ages 19-29), were repeatedly measured while the subjects were tilted 10 degrees head-down for 48 h and while they were seated before (baseline), and after the tilt. An immediate increase in intraocular pressure, measured by pneumatonometer (4.7 +/- 0.6 mm Hg, p less than 0.001) was recorded when subjects assumed the head-down position, and diurnal variations in intraocular pressures were observed for the 48 h. The initial and final head-down intraocular pressures were not significantly different (18.9 +/- 1.2 mm Hg vs. 17.9 +/- 1.4 mm Hg, respectively). However, when subjects resumed the sitting position, intraocular pressures fell below the initial sitting values (14.2 +/- 0.9 pre vs. 11.2 +/- 0.5 post, p less than 0.04). Computer image analysis of the retinal vasculature detected a 6% and 2% reduction in the caliber of arteries and veins, respectively, as compared with sitting baseline values. No changes in visual acuity were documented during the 48 h of head-down tilt. Our data suggest that the choroidal blood reservoir increases in volume over 48 h at continuous head down position with a compensatory decrease in aqueous volume. These findings may explain intraocular pressure changes noted in astronauts during previous space missions and in studies associated with change in body position. PMID- 2241747 TI - Changes in geometrical and biomechanical properties of immature male and female rat tibia. AB - Tibial geometry and mechanical properties in male and female rapidly growing rats were measured to provide comparative data for spaceflight, exercise, or disease experiments that use immature rats as an animal model. A total of 68 immature Sprague-Dawley rats (43-58 d of age) were divided into 8 groups according to age and sex. Tibial length and middiaphysial cross-sectional data were analyzed, and tibial mechanical properties were obtained via three-point bending tests to failure. Results indicated that tibial geometry and mechanical properties were changed significantly during this 15-d period of rapid growth, with male rats having greater increases than female rats. Both male and female tibial lengths nevertheless increased significantly during this growth period, as did middiaphysical cross-sectional area. Tibial flexural rigidity increased significantly for both sexes during this growth period. The male tibiae changed primarily in structural characteristics, but some material properties also changed with age. In the female rats, however, the major changes in mechanical properties of the tibia were attributable only to structural changes in the bone. PMID- 2241748 TI - Hormonal changes after parabolic flight: implications on the development of motion sickness. AB - Twenty-two different humoral parameters including stress-, gastrointestinal- and volume-regulating hormones were measured before and within 45 min after parabolic flight maneuvers of twenty healthy adult subjects. We compared hormonal data of motion sickness-affected participants with those unaffected. Changes in cortisol and vasoactive intestinal peptide plasma levels were significantly different (p less than 0.002 and p less than 0.004) between the two groups with increasing plasma levels of both hormones during motion sickness but decreasing levels within the control group. Growth hormone and prolactin plasma levels increased by 400% and 115% within the motion sickness-affected group and to a smaller degree (120% and 40% increases, respectively) within the control group, while ACTH levels were almost unchanged within both groups. Pancreatic polypeptide and gastrin plasma levels as well as plasma levels of insulin and C-peptide were significantly decreased within both groups after the parabolic flight. Plasma renin, aldosterone, atrial natriuretic peptide and cyclic GMP levels were unchanged within the control group. Within the motion sickness-affected group, plasma renin and aldosterone levels were decreased and atrial natriuretic peptide levels increased after the flight. Humoral parameters of the thyroid gland were neither changed within the groups nor different between the groups. The present data confirm previous results that increases in plasma levels of certain stress hormones participate in motion sickness. Furthermore, increases in vasoactive intestinal peptide levels participate in motion sickness. These increases could explain some of the gastrointestinal symptoms in motion sickness and might serve as markers for a discrimination between regular stress and motion sickness. PMID- 2241749 TI - In-flight stabilization of oxygen saturation by control of altitude for severe respiratory insufficiency. AB - A 4,907-mile medical air transport recently took place between Vancouver, Canada, and London, England. The patient was a 6-year-old boy with multiple pleural, pulmonary, and pericardial hemangiomata who required heart-lung transplant. Because his respiratory function was so poor (including oxygen-induced hypercarbia and sleep-induced hypoxia), a Lear 35 was used. The aircraft made a low altitude flight possible, allowing adjustment of cabin pressure to overcome the child's sensitivity to any significant reduction in partial pressure and to minimize his need for supplemental oxygen. Clinical observation and monitoring using oximetry and transcutaneous blood gas measurements were carried out en route to warn of excessive altitude effects. Sequential increases in altitude were made once oxygenation had stabilized at each cabin pressure. Cabin pressure was not allowed to rise above 3,700 ft to ensure an oxygen saturation level of at least 80%. The transport was accomplished successfully with no requirement for intervention. This approach to in-flight management has applications for other aero-medical transports. PMID- 2241750 TI - Altitude decompression sickness: hyperbaric therapy results in 528 cases. AB - We reviewed 528 cases of decompression sickness (DCS) resulting from altitude exposure (either aircraft or altitude chamber) during the period 1 January 1977 through 31 December 1986, and treated with hyperbaric therapy. Data collected include age, sex, date and place of origin, duty position, type of exposure, altitude, diagnosis, treatment, and result. Analysis of the data described maximum altitudes of exposure, time to onset of symptoms, diagnosis, and the treatment tables used. Significant results include an increased incidence of altitude DCS requiring hyperbaric therapy among females (relative risk for females is 4.3 times that of males), no significant difference in incidence rates between duty positions in the altitude chamber exposures reviewed, and confirmation of the efficacy of hyperbaric oxygen therapy. PMID- 2241751 TI - A case of left hypoglossal neurapraxia following G exposure in a centrifuge. AB - Isolated hypoglossal (XIIth cranial nerve) neurapraxia is a rare clinical presentation. We present a case of an isolated hypoglossal neurapraxia following exposure to +7.2 Gz in a human centrifuge. Although a variety of cervical spine injuries have been reported as a result of G exposure in an aircraft, no cranial nerve injuries have been reported. A review of the literature of isolated hypoglossal neurapraxia is presented with discussion of the probable cause of this nerve injury. PMID- 2241752 TI - Pregnancy outcomes among female flight attendants. AB - Flight attendants have been reported to be at increased risk for menstrual abnormalities and for spontaneous fetal loss. This study examined Washington State birth certificates for associations between adverse pregnancy outcomes and maternal employment as a flight attendant. Current pregnancy outcomes (low birthweight, prematurity, low Apgar scores, and abnormal sex ratio) were not significantly related to occupation. Flight attendants reported their preceding pregnancy resulted in a spontaneous fetal loss nearly twice as often as other women (relative risk = 1.9, 95% confidence interval = 1.3-2.7). However, when comparison was restricted to other employed women, the risk was lower (RR = 1.3, 95% CI = 0.9-1.9). A clinically significant pregnancy risk among flight attendants cannot be excluded on the basis of this study, but the apparent excess risk of spontaneous fetal loss in this and particularly in a previous study could be explained at least in part by methodologic limitations. PMID- 2241753 TI - Positive pressure breathing for acceleration protection and its role in prevention of inflight G-induced loss of consciousness. AB - That pressure breathing for G protection (PBG) can improve both tolerance and endurance to high sustained +Gz acceleration is now well established. It is not surprising, therefore, that the undoubted potential benefits of PBG in an operational environment have been greeted with enthusiasm by aircrew and their commanders. In some quarters, the use of positive pressure breathing (PPB) during periods of high sustained +Gz acceleration is being hailed as a potential cure for the problem of G-induced loss of consciousness (G-LOC). We believe, however, that confidence in the technique for this purpose in modern, highly agile fighter aircraft is misplaced. This article reviews PPB's background and present use as protection against +Gz acceleration, and summarizes the physiologic basis for its effectiveness, before relating it to its undoubted role in support of other anti G strategies. From theoretical considerations supported by published evidence, we conclude that while PPB, if used correctly and when combined with other strategies, can enhance tolerance to +Gz acceleration, its principal influence on the occurrence of G-LOC will be by virtue of its ability to increase endurance by decreasing aircrew fatigue. PMID- 2241754 TI - Partial supination versus Gz protection. AB - Visual and loss of consciousness endpoints during 2 G/s onset G forces sustained for 5 s in 14 and for 10 s in 27 untrained pilots indicated high tolerances when upright, and increases of greater than 3 G when supinated to 60 degrees. Protection against visual symptoms of only 1.1 G when tilted 60 degrees and especially none when experienced subjects were tilted 45 degrees from vertical were unexpected results in 1942. Subsequent findings by others of slight decreases in tolerance at 30 degrees are contrary to hydrostatic basis of G tolerance. Presumably factors other than heart to brain distance (e.g., increased intracranial and intraocular pressures) affect G tolerance when subjects are supinated 30 degrees. We conclude that the apparent increased incidence of G-LOC since the incorporation of 30 degrees seat in F-16 and other fighters in mid 1970's supports the current relevance of these data and suggests that all aircrew should follow the lead of veteran test pilots who sit upright in preparation for and during high G maneuvers (10). PMID- 2241755 TI - A new approach to the analysis of nystagmus: an application for order-statistic filters. AB - A computer program has been designed for the analysis of nystagmus. This program employs a class of nonlinear digital filters called order-statistic (OS) filters. Two OS filters and one linear filter are used. First, the eye-movement signal is smoothed using a predictive finite-impulse response (FIR), median hybrid filter. Then the smoothed signal is processed by a linear band-limited differentiating filter to calculate eye velocity. And finally, the slow-phase velocity (SPV) envelope is extracted from the eye-velocity signal using an adaptive asymmetrically trimmed-mean filter. This approach yields an evenly sampled SPV estimate without resorting to the various interpolation or extrapolation schemes generally used. The adaptive filter estimates SPV based on the local statistical properties of the eye-velocity signal. The adaptive strategy works under the assumption that, on the average, the eyes spend more time in slow-phase than in fast-phase. No assumptions are made about the direction of the nystagmus or the nature of the stimulus used to elicit the nystagmus. This method eliminates all the usual threshold tests and decision logic common to other nystagmus analysis programs. The robust performance of OS filters and the use of adaptive filter structures totally eliminates the need to custom "tune" the program parameters for atypical data sets. PMID- 2241756 TI - Update on possible health effects from exposure to galactic cosmic radiation. PMID- 2241758 TI - Dissociation of sexual arousal and sexual proclivity in the garden snail, Helix aspersa. AB - Sexual arousal (intensity of courtship) and sexual proclivity (tendency to court) in Helix aspersa can be reliably measured using externally observable correlates. Snails with sexual proclivity are significantly more likely to turn toward an anesthetized conspecific after contacting it than are sexually unreceptive snails. Sexual arousal can be inferred from the stage of a snail's genital eversion, which appears only during courtship. The higher the stage of the eversion, the shorter the time required to complete introductory courtship behavior and the higher the rate of successful copulation, the fewer the number of breaks and pauses during courtship, and the longer the time a snail will spend in contact with an anesthetized conspecific. Sexual proclivity has no effect on feeding or locomotory behavior; however, sexual arousal inhibits feeding and increases locomotor activity. Snails that were allowed daily contact with conspecifics required less time to complete introductory courtship behavior relative to snails that were isolated from conspecifics for 1 week. This suggests that daily contact increases sexual arousal. A greater percentage of isolated snails exhibited courtship behavior than did snails which had experienced daily conspecific contact. This suggests that isolation increases sexual proclivity. These differences indicate that sexual arousal is not merely due to an increase in sexual proclivity. PMID- 2241757 TI - Acetylcarnitine reduces the immobility of rats in a despair test (constrained swim). AB - Male rats forced to swim in a cylinder adopted an immobile posture. Immobility was reduced by acetylcarnitine (5, 10, and 20 mg/kg) and by antidepressant drugs, such as desipramine and iproniazid, injected 24, 5, and, again, 1 h prior to behavioral testing. Acetylcarnitine also potentiated the anti-immobility effect of antidepressant drugs in the despair test. Chronic (10 days) treatment with acetylcarnitine mimicked the effect found after acute administration. It is possible that the action of the acetylcarnitine on the despair test is indicative of an antidepressant activity of this drug that is dependent on a change in the sensitivity of monoamine receptors in the brain. PMID- 2241759 TI - Pavlovian conditioning of distinct components of Hermissenda's responses to rotation. AB - In two experiments with the nudibranch mollusk Hermissenda, distinct characteristics of conditioned and unconditioned responses to high-speed orbital rotation were examined. In Experiment 1, two principle unconditioned responses to rotation were identified, namely, reduced rate of locomotion and contraction of the foot. The magnitude of the foot contraction increased throughout a 20-s period of rotation, whereas locomotion was reduced immediately after the onset of the rotation and was maintained at this constant low rate throughout the stimulus presentation. These divergent response patterns suggest that the two responses emerge independently. In Experiment 2, a classical conditioning procedure was employed in which a light (CS) was paired with the rotation (US) employed in Experiment 1. In a subsequent test, it was found that the light had acquired the capability to evoke both foot contraction and decreased locomotion. Although the magnitude of these conditioned responses was reduced relative to the corresponding unconditioned response, the patterns of responding were virtually identical; that is, foot contraction developed gradually whereas locomotion decreased immediately. In contrast, animals that received unpaired presentations of the light and rotation, light alone, or no prior exposure to those stimuli exhibited foot extension in response to the light. These results illustrate a transfer of some of the response-evoking properties of the US to the CS as a result of conditioning, as well as the emergence of two independent conditioned responses. Moreover, these results suggest modulation of at least two distinct motor pathways as a function of learning. PMID- 2241760 TI - Rats with dorsal hippocampal lesions do react to new stimuli but not to spatial changes of known stimuli. AB - The effect of visual distracting stimuli upon the straight alleyway performance of dorsal hippocampectomized Wistar rats was investigated. In comparison with control animals it was observed that dorsal hippocampectomized animals (1) ambulated more during the preexposure phase, (2) acquired at the same rate a running response for food (training phase), (3) reacted similarly to a new visual stimulus (black cards) presented in a sector of the alleyway, and (4) habituated to successive presentations of that stimulus in the same place. (5) However, dorsal hippocampectomized rats did not react, unlike the controls, to the presentation of the same stimulus in another place of the alleyway but (6) reacted to the visual pattern change of the stimulus (now black/white check cards) in the same place. These results indicate that under certain experimental conditions, hippocampus-lesioned animals are capable of interrupting a running response for food in order to explore a new conspicuously located stimulus, habituate to repeated presentations of that stimulus, and to react to a new pattern of visual stimulation. They suggest that hippocampectomized rats do not lose the capacity to react to a new stimulus; the disruption seems to be related to the spatial context of stimulus presentation, supporting a spatial mapping hypothesis of hippocampal function. PMID- 2241761 TI - Social preference of female gerbils (Meriones unguiculatus) as influenced by coat color of males. AB - Female gerbils (Meriones unguiculatus) of three distinct coat colors (agouti, black, and sandy or pink-eyed dilution) were tested in a Y-maze whose arms led to compartments containing unfamiliar male gerbils of varying coat colors. The stimulus animals were separated from the females by a Plexiglas door. The trials lasted for 2 min and each female was exposed to the following four combinations: two males of the same coloring as the female; one male of the same color and another of a different color from the female; both males of different color from the female. The number of crossings to the left and right arms was relayed by photocells to an IBM PC computer. The results indicate that agouti females preferred visiting the arm occupied by agouti males while those of the other coat colors showed no preference for the "wild-type" males. Instead, sandy and black female gerbils preferred to be in proximity with those of non-wild types. PMID- 2241762 TI - Tolerance to the antinociceptive effect of intrathecal morphine in intact and chronic spinal rats. AB - The antinociceptive effect of daily acute intrathecal morphine injections on the tail-flick withdrawal response was compared in Intact rats and rats that were spinally transected 3 to 4 weeks prior to morphine administration (Spinal rats). Spinal rats became tolerant to repeated intrathecal injections of 5, 15, or 30 micrograms of morphine within 3 days. Intact rats were not tolerant to these doses after 4 daily injections. Spinal rats, made tolerant to repeated intrathecal morphine injections, were not tolerant to a subcutaneous injection of 6.0 mg/kg of morphine. These data suggest that, in intact animals, tolerance to the antinociceptive effect of spinal morphine is modulated by descending, supraspinal input. PMID- 2241763 TI - Effect of environmental complexity on size of the superior colliculus. AB - The present study examined effects of environmental complexity on the size of the superior colliculus, a subcortical structure involved in visuomotor functions. Long-Evans hooded rats raised together in a complex environment for 48 weeks were compared with their littermates housed in individual cages. The depth and area of the superficial gray layer of the superior colliculus were about 5-6% greater in the group from the complex environment, while the deeper layers of the superior colliculus showed no significant differences. The magnitude of the differences approached those reported for the neocortex, which has been considered to be distinctive in its morphological responsiveness to differential environmental complexity. The findings also extend previous observations that visual deprivation leads to shrinkage of the superficial gray layer and indicate that the morphology of this subcortical visual area is responsive to varying degrees of environmental stimulation. PMID- 2241764 TI - MVO2max of the heart cannot be determined from uncoupled myocytes. PMID- 2241765 TI - Hydrogen peroxide generation by mitochondria isolated from regionally ischemic and nonischemic dog myocardium. AB - We occluded the left anterior descending coronary artery of anesthetized, open chest dogs, for 1 or 2 h. Some hearts were reperfused for 1 h after 1 h of ischemia. We isolated mitochondria from the central ischemic zone (CIZ) and a surrounding nonischemic zone (NIZ) of the left ventricle, and assayed H2O2 production using a horseradish peroxidase-dual wavelength spectrophotometric technique. Mitochondria, studied in the absence of exogenous respiratory chain inhibitors, generated H2O2 during State 4 respiration with succinate as the substrate. NIZ mitochondria in all groups produced ca. 1.5 nmols H2O2/min/mg protein (no significant differences between groups). The State 4 O2 consumption rates of NIZ mitochondria from hearts subjected to 1 h ischemia plus reperfusion, or 2 h of ischemia (ca. 30 nmols/min/mg) were significantly higher than that of NIZ mitochondria of hearts subjected to only 1 h of ischemia (23 nmols/min/mg). Thus, the ratio between H2O2 produced and State 4 O2 consumption fell from 6.5% to 5%. Mitochondria from all CIZ samples had State 4 O2 consumption rates that were not different from corresponding NIZ values. However CIZ mitochondria of hearts subjected to 1 h ischemia without reperfusion produced less H2O2 (1.1 +/- 0.1 nmols/min/mg), and had a slightly reduced H2O2/O2 ratio (4.4 +/- 0.7%), compared with their NIZ samples (1.5 +/- 0.1 nmols/min/mg; 5.3%). Reperfusion after 1 h of ischemia abolished these regional differences. The CIZ mitochondria from hearts subjected to 2 h ischemia produced only 0.75 +/- 0.22 nmols H2O2/min/mg (2.5% of State 4 O2 consumption). These values were 50% of corresponding NIZ values, and were significantly less than for any other group or tissue region. If similar phenomena occur in conscious animals subjected to incomplete regional ischemia, especially of relatively brief duration or if accompanied by reduced intracellular defenses against oxidants such as H2O2, they suggest that mitochondria persist as H2O2 sources and so may contribute to the oxidant load and myocardial dysfunction. PMID- 2241766 TI - Glycolysis in heart failure: a 31P-NMR and surface fluorometry study. AB - Glycolysis is slow in the heart, especially in the cardiomyopathic heart. Glycolysis is partially rate-limited by phosphofructokinase (PFK), an enzyme which is inhibited by calcium (Ca2+)i and hydrogen ions (H+)i and activated by cAMP. (H+)i and (Ca2+)i are augmented in cardiomyopathy. With glucose as the only substrate (NADH)/(NAD) the phosphorylation potential and developed pressure were significantly lower, and concentrations of phosphomonoester sugars and hydrogen ions (H+)i were significantly higher in isolated cardiomyopathic hearts as compared to healthy hamster hearts. Pyruvate lowered diastolic (Ca2+)i in cardiomyopathic hamster hearts. With pyruvate as the substrate (NADH)/(NAD), the phosphorylation potential and developed pressure increased significantly and concentrations of phosphomonoester sugars (PME), (H+)i and diastolic (Ca2+)i decreased significantly in myopathic hamster hearts. The results suggest that late heart failure in the myopathic hamster is associated with calcium and/or hydrogen ion-induced inhibition of glycolysis. PMID- 2241767 TI - Left ventricular wall stress distribution in chronic pressure and volume overload: effect of normal and depressed contractility on regional stress velocity relations. AB - Regional stress-velocity relations were determined in a first group of patients (n = 15) with normal (five controls, five patients with aortic stenosis, and five patients with aortic insufficiency) and a second group of patients (n = 10) with depressed contractility (five patients with aortic stenosis and five with aortic insufficiency). LV circumferential wall stress was calculated from high-fidelity pressure and frame-by-frame angiocardiographic data using the Wong thick-wall model. Regional wall stress and shortening velocity were calculated from the endo to the epicardium, and from the equator to the apex at 35 points. Regional LV wall stress was in all patients lower at the epi- than the endocardium, and lower at the apex than the equator. Regional stress-velocity relations were downward shifted from the endo- to the epicardium and from the equator to the apex (family of curves) in both groups. At corresponding LV regions stress-velocity relations showed significantly smaller slopes and intercepts (downward depression) in group 2 than in group 1. Thus, wall stress distribution is inhomogeneous in the normal, as well as in the pressure and volume overloaded left ventricle. Regional differences in stress-velocity relations within groups (family of curves) are probably related to changes in preload rather than to changes in regional contractility. Downward depression of the regional stress-velocity relations in group 2 is caused by depressed myocardial contractility. PMID- 2241768 TI - Ultrastructural damage and Ca2(+)-shifts in the canine myocardium subjected to regional incomplete ischemia. AB - The role of Ca2+ in the pathogenesis leading to ischemic myocardial cell death is still controversial. To gain insight into this phenomenon a cytochemical procedure, the phosphate pyroantimonate method, was used to localize different subcellular Ca2(+)-pools at the ultrastructural level. After 45 min of left anterior descending coronary artery (LAD) occlusion, the coronary arteries were perfused with triphenyltetrazoliumchloride staining (TTC) to identify viable ischemic and infarcted tissue. In non-ischemic tissue, Ca2(+)-deposits were confined to the sarcolemma, sarcolemma-derived vesicles, transverse tubules, and intercalated disks. In infarcted tissue (TTC-negative), the sarcolemma lost its Ca2(+)-binding capacity and mitochondria were either overloaded with Ca2(+) precipitate or they contained amorphous densities. In viable ischemic areas (determined with the TTC-technique) the sarcolemma was virtually devoid of Ca2(+) deposits. Mitochondria in this area frequently showed clumping of the cristae, associated with an accumulation of Ca2(+)-precipitate in between the clustered cristae. The results of this study indicate that Ca2(+)-shifts occur in ischemic myocardial cells before the occurrence of other ultrastructural signs of irreversible injury which, therefore, narrows the possibility that Ca2(+) overload is only a consequence of ischemic cell death. PMID- 2241769 TI - Determinants of infarct size in non-human primates. AB - To achieve a better understanding of the major factors that determine infarct size in non-human primates, a mathematical model was constructed using stepwise regression analysis. The model was developed on the basis of infarct size measurements, including the anatomical area at risk, regional myocardial blood flow measurements and hemodynamic determinants obtained in 23 control baboons undergoing up to 2 h of coronary artery thrombosis followed by thrombolysis. In this model, the size of the perfusion bed of the occluded coronary artery and the duration of coronary artery occlusion were found to be the only important predictors of infarct size (expressed as a percentage of left ventricular mass). R2 (square or the multiple correlation coefficient) was 70% in this model. Collateral blood flow and rate-pressure product were not identified as important predictors of infarct size. In a second group of eight baboons, atenolol (0.1 mg.kg-1) was administered intravenously 15 min after the onset of coronary artery thrombosis. Predicted infarct size (based on the mathematical model obtained in the control group) was larger than the observed infarct size in seven out of eight cases. In four instances observed infarct size was smaller than the 95% lower limit of the predicted value. It is concluded that the determinants of infarct size in non-human primates differ from those in canine models with respect to collateral flow and estimates of myocardial oxygen consumption (rate pressure product). The developed mathematical model of infarct size prediction allows the detection of cardioprotective drug effects with an acceptable efficacy. PMID- 2241771 TI - [DNA extraction from body fluids of cadavers]. AB - DNA of 1 ml Ascites, bile, liquor, pleural-exsudate, pericardial-fluid, synovial fluid, urine and vitreous humor of sixteen bodies of either sex was isolated. Applying dot-blot-hybridisation black spots were obtained by using total human DNA as DNA-probe (A), if the origin is human. Our results showed, that body fluids of dead persons contain human DNA, mainly. After rehybridisation with a sex-specific DNA-probe (Y) (pJA 1143) a determination of sex can be performed. PMID- 2241772 TI - [Program of the 68th annual meeting of the German Society of Forensic Medicine, September 19-23, 1989 and of the 1st International Symposium on Alcohol Survey, September 21-22, 1989, Salzburg. Proceedings]. PMID- 2241770 TI - Lidocaine improves survival rate in diabetic rats submitted to acute left coronary artery ligation. AB - This study was designed to evaluate whether the decreased early survival rate of diabetic rats submitted to acute experimental myocardial infarction can be improved by pretreatment with lidocaine. Male Wistar rats (+/- 210 g) were rendered diabetic with i.v. injection of streptozotocin (50 mg/kg), and only those presenting 1 week later a tail-blood glucose value between 250-400 mg/dl were retained in the protocol. Eleven weeks after induction of diabetes, a bolus of lidocaine (2 mg/kg) was administered i.v. about 6 min prior to ligation of the left coronary artery under ether anesthesia in control (n = 54) and diabetic (n = 48) rats; similar studies were conducted in 53 control and 55 diabetic rats without lidocaine pretreatment. Adequate occlusion was confirmed by an elevation of plasma CK-MB levels 4 h later or by a toluidine blue injection technique in rats which died earlier. Rats were followed over 48 h and comparison in the survival rate in each group established with the Fisher's exact test. Early survival rate (measured after 20 min) was significantly decreased in diabetic rats (27% vs 45%; p = 0.04). This was greatly improved by lidocaine pretreatment in diabetic (60% vs 27%; p = 0.0013), but not in control animals (50% vs 45%; p = 0.348). Furthermore, the beneficial effect of prophylactic lidocaine observed early after coronary ligation in diabetic rats was maintained throughout the period of observation (48 h). These data suggest that the prophylactic use of lidocaine is able to reverse the increased incidence of sudden death following experimental myocardial infarction in chronically diabetic rats. PMID- 2241773 TI - [Regulations for autopsy and organ removal in Sweden]. AB - In Sweden clinical autopsies are controlled by the autopsy law, which prescribes information to the relatives about the planned autopsy. Permission by the patient before death or by the relatives after information is mandatory. The performance of the autopsy is not regulated. For forensic autopsies no information or permission is prescribed. The performance and the documentation of the autopsy is strictly regulated and no partial autopsies are permitted. Forensic autopsies must be performed by forensic pathologists. A comparison is made of the legislation in the scandinavian countries and the Federal Republik of Germany. PMID- 2241774 TI - [Ethical aspects of forensic psychiatry expert assessment]. AB - Psychiatrists working in forensic fields are confrontated with different ethical problems. In the following some problems are discussed. At present there is no need of special ethical guidelines for the German forensic psychiatrist. PMID- 2241775 TI - [Lung embolism caused by vaseline following insertion of a venous catheter]. AB - Pulmonary embolism usually is due to natural causes, most often to obstruction of pulmonary arteries by blood clots breaking loose from venous thrombi forming in the leg or pelvis. Clots of other cellular material such as tumor fragments or fatty tissue (this especially in case of severe soft tissue and skeletal trauma), but also foreign material can give rise to this- often times lethal-condition. This is a report of foreign-body pulmonary embolism with obstruction of mainly the right lower lobe pulmonary arteries due to white vaseline embolism, probably responsible for the patient's premature surmise. Clinical history, therapeutic measures and course of disease--including radiographic and laboratory findings are being presented. Autopsy revealed massive pulmonary embolism to the right lower lobe due to a whitish greasy substance, which was chemically identified to be white vaseline. Additionally, this zone of infarction also showed signs of severe pneumonia with abscess formation resembling that of necrotizing infarction and therefore felt to be related to the foreign body embolism. Histology showed evidence of pneumonia and also inflammatory changes of the pulmonary arteries in form of additional formation of endothelium with involvement of the internal elastic layer. Finally, several possible causes for this case of pulmonary vaseline embolism are being discussed. The exact mechanism remains unclear; but in view of the course of disease, some radiographic findings as well as those of autopsy and histology, it seems most likely that the vaseline embolism was connected to transjugular catheterization rather than to the two other mechanisms also described. PMID- 2241776 TI - [Pressure damage of the hypopharynx caused by stomach tubes]. AB - Analysis of 70 cases of death after intensive care of different survival time and various causes of death. All persons were intubated and had nasogastric feeding tubes. Bleedings into the PCA-muscles were found in 50% of all cases (especially in short-term survival: up to 80%). Bleedings in this region are not specifical; there are many possible causes. In 27 cases lesions of the hypopharyngeal wall as the result of pressure by the lying tubes were found up to ulcerations; sometimes just after about 1 day. Frequency and deepness of this lesions increased with the time of survival. Even if the hypopharyngeal wall was intact, there are often circumscripted (histologically detected) destructions inside of the PCA muscle(s), caused in part by the pressure of the tube. PMID- 2241777 TI - [Fatal air embolism following erroneous phlebotomy technique]. AB - An 62 years old patient suffering of polycythemia was treated by phlebotomy. To accelerate the blood flow the collecting apparatus was connected to a pump supplying suction. Of the two pump outlets, providing suction and pressure, the one supplying pressurized air was connected erroneously. Air was insufflated into the arm vein causing cardiac arrest. Reanimation was unsuccessful. The findings are discussed, as well as the difficulties in interpretation. PMID- 2241778 TI - [Carbon monoxide poisoning caused by medical error. Fatalities in connection with medical measures in Leipzig and Hannover]. AB - There are significant differences in the frequency of CO intoxication and its relation to other not natural causes of death between the autopsy cases of Leipzig (DDR) and Hannover (BRD). While the percentage of all autopsies in Leipzig runs up to 7.6%, in Hannover it runs up to only 1.5%. Beside the well known cases of not recognized CO intoxication at the autopsy with or without following intoxication of other persons, two concrete cases of not recognized CO intoxication with the survival of the victims discussed. The not noticed CO intoxication followed by the death of the victim is usually considered in medicolegal opinious as "medical malpractice". In cases of survived not noticed CO intoxications this opinion ist only supposed in special cases with longer anamnesis and a typical seasonal rythmic of symptoms. PMID- 2241779 TI - [HIV-1 prevalence in forensic medicine examination of fatalities (Hamburg and Munich 1989)]. AB - All fatalities investigated at the Institutes of Forensic Medicine in Hamburg and Munich are screened for HIV-1-antibodies. The serological findings of 1,000 consecutive cases in the year 1989 were compared concerning HIV-1-prevalence, riskgroup, age and sex distribution. The prevalence rate of HIV-1-antibodies was 5% in Hamburg and 6% in Munich. The HIV-seropositives were mainly i.v.-drug users and homosexuals dying from unnatural causes. Unexpectedly HIV-infection was also present in two males of advanced age with myocardial infarction. The HIV-1 prevalence rate of all drug related fatalities from 1985-1989 was investigated, too. The cumulated seropositivity in Hamburg was 14% and in Munich 18%. The development was unsteady; continuous monitoring of the HIV-status of drug deaths seems to be a worthful means to evaluate the spread of this disease among the risk group of intravenous drug addicts. PMID- 2241780 TI - [Prevalence of hepatitis B in fatalities in forensic medicine]. AB - Serological screening investigations for hepatitis B were carried out on 1000 sudden and unexpected fatalities from natural causes and non-natural deaths at the Institute for Forensic Medicine in Hamburg. The results were compared with the serological tests of the drug deaths from 1983-1989 and the HIV-infected bodies from 1984-1989. It was found that anti-HBc was positive in 19.2% of the unselected cases as compared with 46.1% in drug related deaths and 73% in the HIV infected group. HBsAg as a marker that expresses infectiosity was present in 15 cases (1.5%) of 1000 unselected cases, 4.4% of the drug related deaths and 15.8% of the HIV-infected group. PMID- 2241781 TI - [Statistical study of alcohol intoxicated female victims of sex offenses]. AB - Comparing 133 presumable rape victims who underwent blood sampling after the event with 2446 alcoholized female traffic offenders it was found that both groups had a delinquency maximum between midnight and 2 a. m. and a delinquency minimum between 6 a. m. and 6 p. m. Most of the rape victims, however, were approximately 5 years younger than the traffic offenders, most of whom were about 25 years old. The time intervals between blood sampling and the event were longer in the case of the rape victims (4 to 20 hours) whereas most traffic offenders underwent blood sampling 1 to 2 hours after the event. At comparable maxima of the distribution curves of blood alcohol concentration (between 1.5% and 2%) that of the rape victims showed a shift to higher values. This is also illustrated by the mean values of blood alcohol concentration at the time of the event: the blood alcohol concentration of the rape victims was 2.24% and thus 0.45% higher than that of the traffic offenders, who averaged only 1.97%. The reason for this is probably to be seen in the different modes of back computation. By assigning 38 offenders to 35 victims it was possible to set up and compare 35 pairs. Comparing the blood alcohol concentrations of all 35 pairs it was found that the blood of the victims contained on average 0.4% more ethanol than the blood of the offenders (1.41% vs. 1.01%). PMID- 2241782 TI - [Cause of death in severe acute ethanol intoxication]. AB - A study of acute alcohol influence (heavy drinker) on sudden unexpected death were analyzed as to age, sex, cause of death and along with the lethal blood alcohol content. Excess alcohol abuse by adults or middle aged women causatived acute intoxication with actual toxic depression of brainstem function (high blood levels, means 3,6 mg/g). Others (alcohol abuse) die by drowning, trauma, sudden coronary death (drinking spirits), cardiomyopathy, hypothermia or hypoglycemia (Diabetes). The autopsy findings are discussed. PMID- 2241783 TI - [Alcohol in Turkish society]. AB - Since the ruin of the Osmanic empire increased the consumption of alcohol in Turkey considerably. Besides the national drink Raki it concerns above all the consumption of beer in the last two decades. The reasons are alterations of the society in the urbanized regions, the consequences are mighty increasing problems with alcoholics, especially among those, who come from the country into the cities, and among women. PMID- 2241784 TI - [Sperm detection using monoclonal antibodies]. AB - Monoclonal antibodies against sperm antigens detect specifically seminal stains in forensic casework. Different monoclonal antibodies resulting from the hybridoma technique allow by means of peroxidase test-system a direct marking of the trace. PMID- 2241785 TI - [Methanol and isopropanol as markers of alcoholism]. AB - Car-drivers, who lost their licence on account of drunkeness, must be tested if the danger of alcoholism exists. The only criterion for this check is the level of bloodalcohol during this case. This check happens mostly one year later. It is proposed to analyse the blood sample immediately after measuring bloodalcohol for markers of chronic or acute abuse to differ alcoholics from persons consuming alcoholic beverages in normal mode. PMID- 2241786 TI - [Forensic medicine aspects of the Remscheid airplane crash]. AB - In December, 1988, an American military pilot obviously losing his orientation brought down his jet fighter into a residential area of Remscheid, FRG. This paper reports on the medicolegal experiences gained during identification the victims. The officials plants for duty in case of disaster are discussed. PMID- 2241787 TI - [Accidents with fatal outcome in Finnish leisure boating 1986-1988]. AB - All 291 fatal accidents (510 persons on board, 318 drowned) in water traffic in Finland in 1986-1988 were investigated by specific teams. Only some data of this extensive investigation are presented in this study. Staggering and falling in boat because of drunkenness, falling over and sinking of boat were the main causes of getting into water of the people aboard. Only 3.5% of the drowned had used life jackets and 9.7% of them could not swim. The reduced ability to swim because of alcohol and the exhaustion were in about half of the drowned the actual cause and the cold water in one third the background factor for drowning. The results indicate that fatal accidents in water traffic are a major problem of males (95.9%) and give important information for countermeasures. PMID- 2241788 TI - [Occasion and risk for detecting driving in alcoholic intoxication]. AB - Detection of offenders driving while intoxicated (DW) (mandatory BAC limit at 0.50%) in Finland was investigated. Almost every fifth offender was detected at road blocks and every tenth of them because of abnormal driving. Compared to the local police the national traffic police had arrested much more offenders for traffic violation (38% vs. 11%) but much less because of accidents (12% vs. 23%). The reason of detection was in a significant way dependent on the following variables: BAC, stage of inebriation, vehicle, day of week and hour of day. The risk of detection is very low, i.e. about 1 to 300. However, the risk has doubled from 1979 to 1984, but thereafter slightly declined. The study provides information for the strategy of the police in traffic supervision. PMID- 2241789 TI - [Diseases of stomach mucosa in the history of alcoholic traffic violators in street traffic]. AB - 425 drunken drivers were examined for their driving sentability. The amount of persons with known diseases of digestion (or gastro-enteritis) among the drivers were higher than the average among the normal population. The patients with ulcus and gastritis showed higher nervosity, depression and emotional instability during the medical examination. In addition they showed a higher degree of openness and a tendency to lower blood alcohol concentrations at previous drunken driving. While judging their sentability (for driving) no differences could be made among persons with and without gastro-enteritis. PMID- 2241790 TI - [Alcohol risk in adolescent drivers--epidemiologic study of the Hannover region]. AB - The traffic in the large cities requires special effort to young traffic participants and persons with just passed driving-license examination. Statistical investigations show an increasing partake of juveniles to alcohol. The results of the research of the protocols of the blood alcohol analyst's office at the Institute of Forensic Medicine of the MHH show an increasing share of drunken young traffic participants with blood alcohol concentrations below 1%. The special risk of juveniles by drinking and driving results not only of the reduction of the physical capacity because of the low alcohol tolerance, but especially of the reduction of the physical capacity and the personality in total. PMID- 2241791 TI - [Possibilities for individual identification of hair roots using DNA probes]. AB - High-molecular weight DNA was extracted from hair roots. The obtained DNA was digested with Hae III and Msp I and transferred to nylon membranes by Southern blotting. The possibility of applying a probe for sex determination (pHY2.1) a "single-locus"-probe (YNH24) as well as a "multi-locus"-probe (M13) was examinated as a function of the amount of hair being supplied. In the laboratory experiment a single hair root was enough for a sex determination or individual identification. Because of methodical difficulties in practice this kind of profiling should only be done with several hair roots. PMID- 2241792 TI - [Significance of functional conclusions for "determination" of the cause of death]. AB - On account of the usual expectation it is often assumed, that an autopsy allows the definitive determination of the manner and cause of death. This paper discusses in a critical way the problems associated with this endeavour. It is often the case, that extensive investigations, associated with structural functional conclusions and consideration of all available evidence are necessary to permit a retrospective interpretation of the course of death. This assumes a scientifically orientated approach to dynamic pathophysiological mechanism. PMID- 2241793 TI - [Premature craniosynostosis--cause of sudden death in children and young adults]. AB - Primary premature craniosynostosis ordinarily leads to characteristic skull abnormalities, if the ossification of the sutures happens in early childhood and involves all sutures, the elevation of intracranial pressure may not cause severe clinical features and the head morphology may be normal. A disproportion between skull capacity and brain volume will be the result. Three cases are reported, where these preconditions combined with exterior effects like minimal trauma, physical activity or consumption of alcohol or medicaments caused sudden death. Important autoptic findings are ossified cranial sutures with the absence of suture lines and increased scalloping of the internal table of the skull (impressiones digitatae). PMID- 2241794 TI - [Spontaneous subdural hemorrhage of natural cause in metastatic renal cell carcinoma]. AB - A 51 years old woman was complaining about pain in the back and headache. Because of sudden change in behaviour she was brought into hospital by her husband. At hospitalization she was unconscious, the first examination showed no hints for trauma. After diagnosis of a bifrontal subdural haematoma intracranial blood was removed twice by neurosurgeons. The woman died six days after hospitalization. The forensic autopsy showed rests of subdural blood and apart of medical intervention no injuries were seen. In the left kidney a carcinoma was found with metastasation in the adrenal glands, the liver, and the dura. The metastasation of the dura had led to destruction of the dural vessels with consecutive subdural bleedings. These hemorrhages probably had been supported by decreased coagulation because of metastasation of the liver. Although such spontaneous non-traumatic subdural bleedings are rare it is obvious that they can cause severe problems by delivering an expert opinion. PMID- 2241795 TI - [Waterhouse-Friderichsen syndrome in adults]. AB - Only a minority of published cases of Waterhouse-Friderichsen-syndrome occurred in adults (Harms et al., 1973). At the autopsy of a 23 years old woman there were found sugillations of the eyelid, of the peri- and epicard, of the serosa of the small intestine and of the lung. In the region of the adrenal gland a brownish red mass was detectable. Histologically an adrenal apoplexy with necrosis and in liver, spleen and lung a lot of neutrophils were seen. Streptococcus viridans was pointed out in the blood. PMID- 2241796 TI - [A case of amyloidosis of peripheral arteries of the heart and liver in an elderly patient]. AB - Cases of isolated cardiac amyloidosis and amyloidosis of the liver are seldom mentioned in the literature (Pitkanen et al., 1984). At the autopsy of a 85 years old woman we found a severe common arteriosclerosis, especially of the brain and heart. A pacemaker was regularly implanted. By staining with Kongo red there was histologically shown an isolated amyloidosis of the peripheral heart and liver arteries. PMID- 2241797 TI - [Myofibril degeneration of heart muscle: histologic picture and pathophysiologic significance]. AB - Mechanical trauma to the heart induces a rhythmical transverse banding of adjacent myocytes. This finding is due to hypercontraction (true contraction bands) and it is different from the cross band type myofibrillar degeneration (MFD) which is characterized by disseminated foci of irregular transverse banding. This latter type is mainly found after temporary myocardial ischemia, in cases of reanimation using catecholamines and defibrillation as well as in severe brain trauma. Both types of cross banding can be identified in hematoxylin and eosin or in azan stains; a much better visualization is obtained using the PTAH or the Luxol Fast Blue (LBF) method. Moreover, LFB, giving a selective blue staining of the damaged cells, allows the identification of the recently described diffuse type MFD. Well developed contraction bands may indicate the vitality of a heart trauma, yet a supravital occurrence seems to be possible. MFD, diffuse or cross band type, clearly correlates with high blood catecholamine levels at the time of death. PMID- 2241798 TI - [Myofibril degeneration of heart muscle: diagnostic value of selected forensic pathology case material]. AB - Information on the incidence of myofibrillary degeneration (MFD) was obtained by investigating the hearts of seven groups of cases with different forensic diagnosis using luxol fast blue as a staining method. The following diagnostic groups were examined: acute morphine intoxication, acute carbon monoxide intoxication, hanging, strangling by hand and/or ligature, drowning, acute hemorrhagic shock and sudden infant death syndrome. MFD positive cases were found in all diagnostic groups, but the morphologic expression of MFD as well the number of cases per group differed: The phenomenon of cytoplasmatic banding could be observed in nearly all cases of hanging, strangling and acute hemorrhagic shock; the phenomenon of diffuse cytoplasmatic staining in most cases of drowning. The diagnostic importance is discussed. PMID- 2241799 TI - [Sudden death of cardiac origin in childhood and adolescence]. AB - In the autopsy material performed by our institute during the years 1979-1988, in the age group under 18 years (total 680 cases) 57 cases of sudden cardiac death (8%) were found. 49.1% of them were due to congenital heart malformations, 38.6% were due to myocarditis. The age distribution, the male:female--ratio and the conditions of occurrence showed significant differences. At heart malformation, the death frequently was due to ischemic damage of the myocardium. For the examination of sudden death cases as a main purpose of forensic medicine, general pathologic biopsy-diagnostic regimen did not seem to be fully apted. This is a challenge for establishing an international comparable general accepted nomenclature and methodology, that suits to this purpose. PMID- 2241800 TI - [Sudden cardiac death in mitral valve prolapse syndrome?]. AB - Primary mitral valve prolapse is considered a rare cause of sudden cardiac death. Close to 100 cases are documented worldwide. The cause of death seems to be cardiac arrhythmia, so postmortal diagnosis is difficult and depends on severe changes of the mitral leaflets and--sometimes--on anamnesis. Three postmortem cases are presented, where a sudden cardiac death apparently was caused by mitral valve prolapse or its complications. PMID- 2241801 TI - [Sexual dimorphism of the corpus callosum?]. AB - Morphometric studies carried out during the past years have led to the assumption that the splenium of the corpus callosum in the female brain is significantly larger in size and more bulbous than in the case of men. This result, obtained by the examination of a relatively small number of samples, was to be checked by investigations with a larger number of samples. Our own planimetric studies were based on a total of 70 dissection cases and 55 nucleal magnetic tomograms (NMR), both evenly distributed among men and woman. When applying the identical measuring parameters as those used by the above cited authors, a sexual dimorphism could not be confirmed. This result did also not change when additional modified measuring parameters were taken into consideration. PMID- 2241802 TI - [Computer-assisted identification and comparative studies of the human skull]. AB - The comparison of reconstructed skull profiles with photographic or other patterns for identification up to the reply to questions for sex, age, and race by the help of image analysis represents a relatively new development in forensic medicine. Using a Robotron image analyzing system 20 human skulls of different races were analysed morphometrically. Standardized profile functions, which were put through a morphometric analysis, showed characteristic individual features. By the help of the computerbased identification method mathematic differences between skulls of varions races became veritable. PMID- 2241803 TI - [Quantitative studies of mast cell proliferation at the wound edge --rate of DNA synthesis in intravital and postmortem biopsy]. AB - The number of DNA synthesizing mast cells in experimental induced wounds was calculated using bromodeoxyuridine as a DNA marker and naphthol AS-D chloroacetate esterase as a mast cell marker. After different survival times, specimens of the wound edge were taken before death and 24 hs after death. At a survival time of 48 hs in vital biopsy the number of DNA synthesizing mast cells peaked, at 72 hs and fell after a period of 8 days. Even though an identical kinetic course was demonstrable in cases of postmortal biopsies the percentage at each survival period was significantly lower than in vital biopsies. PMID- 2241804 TI - [Do bacteriologic-chemical drinking water studies of households with suspected SIDS have significance?]. AB - In 30 households with SIDS the drinking-water was studied microbiologically and chemically regarding its bacteriological contents, also it was checked for Pb and Cu. Three test solutions of 45 bacteriologically researched samples revealed significant data. One sample showed 2400 cfu "colony forming unit" which is more than double the number of germs permissable in an drinking-water container according to the standards of drinking-water (TrinkwV) 1(3). Also Ps. aeruginosa were found. A further sample contained 3300 cfu Coliforme (E. cloace in 100 ml). The lower quality of a further samples with 2.6 x 10(6) cfu could be retrospectively explained by works done by the Berlin City Works (Berliner Wasserwerke). Enteric bacteria could not be revealed. The remaining 42 samples were within the criteria Section 1 [(1), (2), (3)] of the drinking-water standard. Samples which fulfilled the norms of Section 1 (3) TrinkwV for reserve containers with up to 1000 cfu can be explained by the known fact that water in pipes (containers) can easily be contaminated from outside, for instance through germs like Pseudomonades. In none of the samples a connection between water quality and bacteriological post-mortem findings could be found. In two groups concerning the research for heavy metal the amount of Pb did not surpass the limit of drinking-water standards. In several cases the amount of Cu surpassed that of Pb. Bacteriological-chemical water research in households with suspicion of SIDS are only useful if anamnestical, clinical and autoptic data can be brought into a close temporary and spatial order and if the findings can be controlled through repeated research.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241805 TI - [Morphometric studies of the lung in shock of various etiologies]. AB - The early schocklung-syndrome was investigated by morphological and morphometrical methods in order to discriminate the influence of different etiological factors on shock. Survival times up to 11 days were included in the investigation. We compared lungs from polytrauma with and without lung contusion and lungs after hypovolemic shock due to sharp violence. Cases of immediate death after brain damage served as controls. Apart from well known parameters of the shocklung--interstitial edema with increase of lung weight, intravasal sticking of granulocytes etc.--lymphangiektasy proved to be a reliable parameter to differentiate the temporal and etiological development of shock. PMID- 2241806 TI - [Criminal circumstances and picture of intentional physical injuries (with special reference to the use of weapons)]. PMID- 2241807 TI - [Non-strangulation-induced injuries of the larynx and hyoid bone]. AB - Injuries of the larynx and hyoid bone resulting from forces other than compression of the neck were found in 129 of 5591 cases (2.3%) of medico-legal autopsies performed between 1978-1987. Victims of blunt trauma showed these fractures in 6.7%, victims of incides or stab wounds in 9.2%, other cases in 0.4%. The results were compared with clinical observations of laryngotracheal trauma. PMID- 2241808 TI - [Recent developments of sex determination using various skeletal sections]. AB - Sexualdimorphism of the skull characterized by morphological marks. Practical applications and the value represented. Epiphysial breadth of the long bones well qualified for difference sex of the bones, demonstrated by new measurements of 314 bones from adult persons. Stepwise regressions- and discriminant-analysis verify the results. Reference of the influence of acceleration and type of constitution complete the study of identification. Analysis of pictures from living persons using also pattern of the lip and marks of the ear. PMID- 2241809 TI - [Massive pulmonary brain tissue embolism]. AB - A 20 year old woman with a severe head injury and rapidly increasing brain edema died 46 hours after the accident. There was clinical evidence of protracted shock and disseminated intravascular coagulation. The autopsy revealed a macro embolization of brain tissue of the lungs with many central and intermediate lung artery branches occluded by cerebral tissue. Preconditions of the brain tissue embolism were a severe fracture of the skull including a traumatic rupture of the right sigmoid sinus, together with a local brain laceration and an extremely elevated intracranial pressure. Fibrin precipitations were prominent at the surfaces of the brain tissue emboli as well as in peripheral blood vessels of the lung; in the systemic circulation, intravascular coagulation was much less pronounced. PMID- 2241810 TI - [Myoglobin concentrations of cadaver blood in fatal electric injuries]. AB - In cases of death due to electrical current frequently autopsies do not reveal makroscopic findings. Recent reports indicated, that an increased concentration of myoglobin in blood sampled from the heart and femoral vein as a sign of membraneous alteration related to electrical current passing the human body is applicable to prove death from electricity, as far as other factors extremely influencing myoglobin concentration can be excluded. Determination of myoglobin by radioimmunoassay performed on 5 cases of death caused by electrical current, 3 cases of sudden death due to heart disease and several other causes of death did not verify any correlation between myoglobin concentration and causes of death. PMID- 2241811 TI - [Effect of various technical parameters on potential danger of an electric injury in the bathtub]. AB - In contrast to common beliefs there is not strict necessity for lethal danger during electric shock in a bathtub. Measurements of the electric field demonstrates the ground conditions and water temperature are of vital importance as are a variety of other parameters. With an electronic amplifier especially designed for this problem measurement of the electric parameters in the water was made possible. PMID- 2241812 TI - [Heart current density as the most important biological parameter of electrocution in the bathtub]. AB - The most important factor during electrocution in a bathtub is the amount of current flowing through a body, not the amount of voltage. A method of measurement is introduced which--under simulation of various electrical situations--provides the possibility to measure the current flowing through the heart and to determine it's direction and density in the tissue. Hereby a ranking of the different factors influencing electrocution can be set up. PMID- 2241813 TI - [Fatal shotgun use in peace time]. AB - On the suggestion of Conzelmann et al. (1977) and Lerch (1982), 176 shooting fatalities with 249 shot wounds in the South Baden region were evaluated in a multi-dimensional analysis of such data as place of death, autopsy findings, forensic examinations, and police and court files. Data were collected on incident, victim, culprit, weapon used, motive and the special circumstances of each case. The greatest number of deaths are suicides of inebriated men using handguns of medium-size caliber (7.65 and 9 mm), followed by homicidal shooting deaths, some involving multiple shots at longer range, though one-third were at close range. 78% of the shots fired from rifles and shotguns were in connection with suicides, 50% involved small-caliber weapon, 86% of the victims were men. Only 7% of the 131 shooting suicides, but 36% of the 39 homicides, involved women. 58% of the women who died a shooting death were victims (not seldom followed by their mates committing suicide), men were victims in only 17% of the cases. 98% of the suicidal and one-third of the homicidal shots were fired at close range. Rifles or shotguns were used in 12% of the homicides, but also in 27% of the suicides. Yet according to witnesses, every 10th victim, though mortally wounded in the head, chest, or abdomen, was still capable of action for some time. Every 7th suicides was still clutching the weapon after death. Half of the suicides involving unusual shots were committed by women. In 50% of the homicides, the killer was either the mate or a relative of the victim, was between 40 and 60 years of age, and committed suicide after shooting his mate. In 78% of the cases, killer and victim knew each other. Two-thirds of all the suicides occurred in the home, with the bedroom being the preferred scene in 25% of the cases. PMID- 2241814 TI - [Case analysis of double or multiple homicides]. AB - Thirty-six patients (the youngest was about one and a half years old, and the oldest 76 years old) were the victims of double or multiple homicides. These comprised a total of 16 homicides, exclusively involving one perpetrator. Seven of these could not be categorized in the group of "family tragedies". These crimes are of particular medical-criminalistic interest in view of their constellation. The way in which the murder weapon was used, the situation dependence as well as the behavior of the perpetrator after committing the crime are discussed in detail. PMID- 2241815 TI - [Theft with subsequent murder]. AB - We studied 39 cases from autopsies made between 1978 and 1988 in the Institut fur Rechtsmedizin der Freien Universitat Berlin and the Landesinstitut fur gerichtliche und soziale Medizin Berlin in which the public prosecutor's office had investigated about robbery in coincidence with killing. The average age of the victims was 75 years, the average age of the perpetrators was 21 years. One third of the victims died because of bronchopneumonia. 5 victims only showed slight injuries, the autopsy showed no definite cause of death, but we found severe signs of illness of the organs resp. of the heart. In these cases we diagnosed a "psycho-physiological cause of death". One third of the victims had a severe stenosis of the coronary system and one third showed cardiac hypertrophy of over 450 g. Head and face had been the favorite target of the perpetrators. Most localisations of crime had been the apartments of the victims and the booty often was less than DM 100,-. 75% of the perpetrators had been previously convicted. In the cases with "psycho-physiological" cause of death the court condemned the perpetrators only because of booty but never because of killing. PMID- 2241816 TI - [Diurnal correlation of criminal behavior]. AB - In order to study the correlation between criminal acts and time of day we analyzed reports of the Federal Police Department in Salzburg covering 2 months as well as our own psychiatric expert-opinius in cases of robbery and homicide. Offences against property have the same day-time rhythm as does regular labour. Alcoholic intoxication hardly occurs with offences against property, although the activity of burglars goes over into the early hours of night. Aggressive offences are commonly accompanied by alcoholic intoxication, they are mainly observed at night. Less aggressive offences such as maltreatment or fighting generally occur during the late afternoon until midnight. Whereas aggressive offences of alcoholized persist throughout later hours of the night. The delinquency of robbery and homicide continues into the early hours of the morning. In cases of homicide there are differences concerning the individual conflict-situation. Homicides in connection with family tragedies or partnership conflicts usually occur during the afternoon or the early evening and show just a minor connection with alcoholization. Homicides in the course of primitive conflicts appear highly correlated to alcoholization and to the night hours. In cases of homicide of mental-patients there is no general connection with alcoholization nor can there be seen a day-time correlation. PMID- 2241817 TI - [Autopsy of accident victims--incidence and criteria for selection]. AB - In a first analysis the frequencies of autopsies in the area district of Karl Marx-Stadt (Chemnitz) are investigated in respect to types of accident, sex and age groups. Victims of traffic- and working accidents are dissected in far more than 50% of all cases (predominantly with forensic medicine) because of the obvious legal consequences; accident occurring at home or during leisure are paid less attention to. Possible criteria for selection are discussed. PMID- 2241819 TI - [Analysis of the mechanism of tibial injury in cases of automobile-pedestrian collisions]. AB - The type and the mechanism of development of lower extremity injuries suffered during traffic accidents between cars and pedestrians were studied in 93 accidents with frontal or almost frontal collision. Evaluation was based upon the facts of the investigation and the opinions of medical and technical experts. In 28% of the cases lower extremity injuries were not demonstrable, in 21% of the cases there were only soft part injuries at the site of primary collision, while in 51% bone fractures were also diagnosed. The collision speed and the injury severity score (ISS) are in a statistically significant correlation. In the case of lower extremity injuries, in higher speed categories, such definite correlation was demonstrable only for injured persons over 60 years of age, and no such correlation existed for younger people. This difference is explained by age-related biological differences (osteoporosis, reduced elasticity). PMID- 2241818 TI - [Forensic-toxicologic detection of pholcodine in urine and hair]. AB - Pholcodine (3-morpholinoethyl-morphine) is used in many countries as an antitussive without analgesic or addictive properties. It is of forensic significance that pholcodine interferes with opiate immunoassays. In this article a GC-MS procedure for the detection of pholcodine in urine and hair is described and its efficiency as a confirmatory test for fluorescence polarisation immunological and radio immunological results is reported. PMID- 2241820 TI - [Role of collision velocity in traffic accidents involving automobiles and pedestrians]. AB - On the basis of facts of the investigation and medical as well as technical experts' opinion on traffic accidents that happened between cars and pedestrians in Budapest in 1986, the authors studied the role of the travelling speed and collision speed in the severity of injuries suffered. They concluded that a 20% reduction of the 60 km per hour speed limit currently valid in inhabited areas in Hungary, i.e. compliance with the European standard, would reduce the number of fatal traffic accidents by as much as 40%, and the mean severity score of injuries suffered would decrease from ISS 26.90 to ISS 19.96. PMID- 2241821 TI - [The pedestrian-automobile accident at lower velocity. Experimental studies of biomechanical and clinico-prognostic topics]. AB - The influence of bumper configuration on injury patterns resulting from car/pedestrian collisions were analyzed. 18 experimental settings were carried out on the deceleration device of the Institute of Forensic Medicine of the Medizinische Hochschule Hannover using a middle class passenger car at collision speed of 32 km/h. Three modifications of the standard bumper design did not reduce the severity of injuries induced by collision. Comparatively promising results were given by another bumper construction consisting of an additional bumper relatively easy to deform attached to the standard variant at a level of 12 cm below. Authors discuss findings regarding injury patterns, injury mechanisms and subsequent implications. Based on trauma surgeons' experience it is suggested not only to aim on reduction of bone injuries. Major attention has to be paid on improving rehabilitation prognosis and on reducing medical treatment expenses. According to data available soft tissue damage is of major importance and needs to be quantified before taking one particular bumper construction as pedestrian friendly design. PMID- 2241822 TI - [Driving fitness of female headache patients in tests of traffic medicine--a psychotechnical investigation]. AB - To detect differences in psychophysical performance during pain attacks and pain free intervals, 30 female patients aged 21 to 58 years and suffering from attacks of headache were investigated intraindividually by means of established test methods (attention quotient according to Gruner, motorial accomplishment series according to Schoppe and achievement testing device). The patients were randomized and assigned either to Group A (first test while having pain) or Group B (first test without pain). The patients were also asked to assess the intensity of their headaches. The hypothesis that "headaches do not impair psychophysical performance" was refuted by the significant results obtained in all tests, the observed deficits concerned predominantly achievements in the field of concentration, achievements which are also required for operating a motor vehicle. PMID- 2241823 TI - [The carbon monoxide content of muscles]. PMID- 2241824 TI - [Practical value of post-mortem electrical excitability in determining time of death]. AB - In 35 cases (about 200 single excitations) electrical excitibility of mimic muscles was reexamined according to the method developed by Klein and Klein (1978) with subjective grading of muscular reaction according to the intensity and spread of movement. Instead of "rectangular-like impulses" of some ms duration in a repetition of 30 to 70/sec and 50 V constant-current rectangular impulse of 1 sec duration and 30 mA were used. Nevertheless the determination of the time since death is valid within the calculated 95%--limits of confidence. The 95%--limits of confidence are not valid for cases of fatal hypothermia: here are longer (and shorter) times possible for the special degree. In our opinion examination of electrical excitibility belongs to the minimal standard of methods to be used for determining the time since death in the early postmortem interval. This is discussed in 17 cases where the dates for the special degree of electrical excitability could narrow down the time period since death given by the nomogromn method. PMID- 2241826 TI - [Differentiation between in-life and post-mortem hemorrhage]. AB - The determination of the time of haemorrhaging can be of substantial importance in the forensic practice. Histological, immunohistochemical and morphometric investigations were carried out on haemorrhages from animal experiments and from human pathological samples. Centrifugal topology, serum-erythrocyte discontinuity, topological arrangement of Fibrin formation and stabilisation of Factor XIII A were evaluated as criteria to define antemortal origin of haemorrhages. PMID- 2241825 TI - [Parameters for determining the time of death from post-mortem muscle contraction -precision of assessing time of death]. AB - The objectified muscular contraction on excitation with rectangular impulses of 1 sec duration and definite current intensity is in its postmortem course characterised by: 1. Change of the shape of muscular contraction (time-course of muscular contraction) from a two peak to a one peak shape 2. postmortem decrease of the maximum force of muscular contraction on definite current intensity 3. increase of the relaxation time of muscular contraction. On an random sample of fifty bodies decrease of the maximum force and increase of the relaxation time as criteria for extrapolating the time since death were investigated. The extrapolation was performed on the basis of the regression between ln of the maximum force and time using the mean values for slope and intercept and the regression between ln of the relaxation time and the ln of the time since death respectively using the mean values for slope and intercept too. On fifty bodies the calculated 95%--limits of confidence are +/- 2.85 h (decrease of the maximum force) and +/- 2.7 h (increase of relaxation time) up to 13 hpm. The calculated 95% limits of confidence were examined on an independent random sample of 20 bodies and proved to be reliable. PMID- 2241827 TI - [Two conspicuous findings in human tubular bones following longer exposure time]. AB - A human skeleton was found in a forest after an aging time (laydays) of nearly three years. Surprisingly a larger number of living maggots crawled out of the medullary cavity of the humerus after sawing it longitudinally. Investigations of other long bones showed remnants of maggots, fly-pupas and maggot-excrements in similar cases. A humerus is found after an estimated aging time of over 100 years. The presence of a remaining epiphyseal gap indicated an age of about 20 years, whereas the extension of the medullary cavity showed a much higher age. After a long aging time, these structures show similar findings in other cases. Damage done by frost should be discussed. PMID- 2241828 TI - [Detection of drugs in sweat]. AB - This study investigates the presence of drugs in apocrine sweat. The samples were collected from the axillary perspiration of 25 hs. The determination of the drugs was performed by radioimmunoassay. The concentrations measured represent the sum of drugs and there metabolites. Measurable drugs concentrations of THC, benzodiazepine, cocaine, barbiturate, morphine, methadone and cotinine were found in all samples. The presence of the drugs in the sweat was manifested also by GC/MS. PMID- 2241829 TI - [Preservation of human cadavers throughout history--a contribution to development and methodology]. AB - From ancient times to nowadays man tried out of different intentions to keep the bodies of dead persons in the best possible state of preservation. The embalming procedures primary aim at avoiding or at least stopping rottness and autolysis. They have to change depending on the technical possibilities and further destiny of the embalmed bodies. Beside a short historical review we present the method used at our institute. PMID- 2241830 TI - [How to expose fraudulent expert witnesses]. AB - In our courtrooms you can meet, up to this day, experts of dubious qualities if not mere shams and deceivers. They are found in all sciences, but also in pseudo sciences as paramedicine and parapsychology. In any case such expert pretenders must be exposed by the judge to prevent dangerous miscarriage of justice. Examples are given how to unmask the fraudulent rascals. PMID- 2241831 TI - [Expert systems in forensic medicine. Pilot project in the differential diagnosis of death caused by hanging]. AB - The special field of legal medicine represents a very heterogeneous science, which makes it impossible, that a forensic pathologist could be an "expert" in all areas. The most recent achievements of computer-technology have opened up the possibility of being able to use a PC to produce an "expert system", for with large computer programs are needed. Therefore we wanted to test in a pilot project, if it was possible to establish an expert system, which was suitable for supporting forensic pathological diagnosis. We confined ourselves to the differential diagnosis of "death by hanging" where a clear line between vital and postmortal events, respectively suicide, homicide and accident was drawn. The discrepancy between the relatively scanty amount of statistically reliable data on the one hand and the complexity of the manifestation of death by hanging on the other hand proved to be the main problem. Although we are not yet able to make an expert system available which meets all our requirements, we are convinced, that in the future computer-aided diagnosis may be of great use for work in legal medicine. PMID- 2241832 TI - [WHO basic classification in forensic medicine]. AB - The internationally used WHO-basic tabulation list of causes of diseases and death is presented in a modified version for forensic medicine. The findings of postmortems are to be indexed with this code and put into a database. We would like to suggest that as many institutes as possible use this code and collaborate to discuss further modifications. PMID- 2241833 TI - [Forensic medicine literature databank. Goals and uses]. AB - In addition to existing, international database systems we started building up a forensic-medical database. Whereas the current systems offer a cross section of the newest medical knowledge, we wanted to reach a review over the most important journals specialized in forensic medicine, starting from their beginning. In this way one gets informations over empirical knowledge and casuistry, which are of great importance in forensic medicine. As technical basis we use a personal computer and the dBase III database system. PMID- 2241834 TI - [Calcium concentration in vitreous humor--a means for determining time of death?]. AB - Several authors are in agreement that there is no relationship between calcium concentration in vitreous humor and time since death. Nowak and Balabanova (1989) however established such a relationship on a random sample of 19 cases suffering from heart disease (coronary occlusion) and quote Coe (1969, 1972) who "described also a correlation between PMI and calcium" which is completely wrong. The results of Nowak and Balabanova are compared to own results (n = 270, 69 deaths due to coronary artery disease), results of Sturner et al. (1972) and Schmidt (1988). In conclusion there is a statistically significant correlation between calcium concentration in vitreous humor and PMI (r = 0,356) but the range of scatter of the individual calcium values over the PMI is so great that it becomes clear that vitreous calcium is no aid in estimating the time since death. PMID- 2241835 TI - [Postmortem increase in the galvanic threshold]. AB - The investigations of Joachim and Feldmann (1980) on the postmortem rise of muscular threshold were examined on a random sample of 20 bodies with known time of death. Muscular reaction on excitation was objectified using a sensitive force transducer pricked into the muscle (mostly thenar). The muscle was excitated (each half on hour) using rectangular impulses of 1 sec. duration with a current intensity which causes a muscular contraction of 2.5 mN until a current intensity of 80 mA doesn't reach this force any more. Ln of muscular threshold and time since death show a strong linear relationship (r = 0.965). Time since death was extrapolated with mean values for slope and intercept (calculated from the random sample) for all measured values of muscular threshold. Extrapolation from a single value with mean values also for the slope reveals a much more precise estimation of the time since death than extrapolation with an individual slope (according to Joachim) which requires repeated measurements of muscular threshold in an interval of 30 minutes. The procedure was examined at a random sample of 8 cases. The real time since death war always within the 95% limits of confidence of the calculated time since death. PMID- 2241836 TI - [Injury patterns and roentgen findings in gunshot wounds with rare flint ammunition]. AB - Smoothbore shotgun barrels can fire cartridges with common pellet loads as well as shotgun slugs and rubber bullets. Other than conventional shot, the cylindrical Brenneke-type rifled shotgun slugs sometimes cause perforating wounds. The shotgun ammunition for use in self-defence can have a single projectile or several rubber pellets. Where the propellant is black powder, short range shots will probably leave searing marks and intensive soot deposits. Fired at close range, rubber bullets can penetrate through the skin into the body, fired at greater distance they cause contusions. A case of homicide (repeated firing with a 12-ga. pump gun) is used to present and discuss the injury patterns and X-ray findings after impact of Brenneke-type slugs and rubber bullets as well as of "classical" shot pellets. PMID- 2241837 TI - [Comparative studies of drug detection using recent immunologic methods]. AB - 150 urine samples which we received from the criminal investigation department were measured with EMIT cannabis 20 and EMIT cannabis 50 reagents by EMIT Autolabsystem and especially with the immunoassay analyzer ETS by Syva Diagnostica. The confirming analyses were performed by GC-MS. If only cases are considered which are positive with cannabis 20 containing at least 10 ng 11-Nor delta-9-THC-9-carboxylic acid in urine, there will be a negative result of 18.8% with EMIT 50. This appears to be unreasonably high. Some of these cases were also tested with Abuscreen ONTRAK-reagents. With this method the cut off for cannabis with 100 ng/ml urine is far too high but can be lowered essentially by taking a larger urine sample. PMID- 2241838 TI - [Ketotifen poisoning in infancy?]. AB - A male baby aged 3 1/2 months died about 3 hours after application of ketotifen due to chyme aspiration. Apart from a mycotic napkin rash the post-mortem examination did not show any other pre-existing pathological findings. When analysing blood samples toxicologically we observed a remarkably high concentration of ketotifen whereas the urine level was comparatively low. The morphological and toxicological findings are presented and discussed in differential diagnosis with reference to sudden infant death syndrome. PMID- 2241840 TI - ["Alcohol associated" death in a forensic medicine autopsy sample at the Berlin Free University]. AB - From 1978 to 1988 6431 forensic postmortem examinations have been made at the Freie Universitat Berlin. These are about 50% of all p. m. examinations in Berlin (West) of the corresponding period. 22% of these cases were associated with alcohol. On one hand there was an acute influence of alcohol, on the other hand there were indications of chronic alcoholism. A rise of alcohol associated cases or of alcohol concentrations could not be found out. PMID- 2241839 TI - [Urine analysis for legal confirmation in opiate addicts]. AB - Urine samples of 31 probands who had come in conflict with the Dangerous Drugs act and therefore had to take part in urinalysis tests where analysed during a period of 34 months. The purpose of this study was to find out whether urinalysis testing can reduce drug abuse. The urine samples were tested on morphine/codeine, cannabis and barbiturates. 28 out of 31 persons were to be tested on morphine, 13 on cannabis and 26 on barbiturates. 32% of the persons tested on morphine showed no positive results during the whole period of investigation. 3% had continuous relapses (greater than 30% positive results) during this time. A significant (x2 = 28.98) decrease of positive samples at the end of the investigation period was found. The tests on barbiturates showed no significant (x2 = 0) influence of the urinalysis on the frequency of positive results. Tests on cannabis showed a slightly significant (x2 = 4.26) increase of positive results at the end of the investigation period. Most of the test persons showed an obvious improvement of their social and family conditions during this period. PMID- 2241841 TI - [Fatal intoxication following rectal instillation of alcohol]. AB - A 62-year old man who had been living on a remote farm was found dead in his bed. Inserted in his rectum was a synthetic flexible tube filled with brandy (43 vol. %) and connected to a bicycle pump. Samples taken during autopsy from 3 different parts of the body showed ethanol concentrations from 4.87% to 5.35% in the blood and 6.73% in the urine. The ethanol concentrations in the small and large intestine were considerably higher (more than 29%) than in the stomach (9%). The decreased had a tumor as large as a tennis ball on the base of his tongue, almost completely filling the oropharynx, making swallowing very difficult, which probably was the reason of the rectal instillation of alcohol. The report deals with this unusual case of rectal alcohol instillation, and with the different ethanol and congener alcohol concentrations in the body fluids. PMID- 2241842 TI - [Suicidal electric fatalities outside the bathtub (with 3 case reports)]. AB - Three cases of suicides due to electricity, which happened outside the bathtub, are presented. In favour of suicide there spoke farewell letters, the situation of discovery or known depressive personality changes. In all three cases it was about male persons at the age of 19, 30 and 50. Low-voltage electricity was used. The locations chosen for the employed electric cables were: right wrist/left ankle or right and left wrist. The electric marks showed a circular continuous form with different breadth, partly associated with carbonization. In one case over the normal clothes there were worn a ski suit and an integral helmet; the flow of electric current was regulated by a timer. PMID- 2241843 TI - [Sudden death of natural internal cause: endocarditis ulceropolyposa]. AB - There is an increasing tendency amongst the general population towards rejection of conventional medical therapeutic measures, particularly certain types of medication such as antibiotics. Alternative modes of treatment, often undertaken independently by the patient, are favoured. Because of this, diseases that have become less frequent have acquired new significance as the cause of sudden unexpected death. This problem is illustrated with the case of a 20-year-old woman who died as a result of inadequate treatment of subacute bacterial endocarditis (endocarditis ulceropolyposa). PMID- 2241844 TI - [Serum testosterone concentrations in cannabis and opiate users]. AB - The object of this study was to establish possible influences of long-term cannabis usage on plasma testosterone levels. The plasma testosterone levels of 66 male Pakistani who for years had smoked cannabis daily or drank cannabis regularly where measured after chronic and acute intake of the drug and compared with a material of 41 normal controls, i.e. persons who did not use cannabis. An evaluation of the results showed that there were no significant differences between the two groups. No influence of long-term cannabis usage on plasma testosterone levels was found. Furthermore we wished to find out wether long-term heroin abuse showed an effect on plasma testosterone levels. The concentrations of testosterone in the plasma of 102 heroin addicts assigned to a Methadone Program were measured and compared with the values of 29 male healthy students as controls. Plasma testosterone levels were found to be significantly decreased in heroin addicts as compared to controls. PMID- 2241845 TI - [Iatrogenic cardiac tamponade in lung embolism]. AB - A 65 year old man with diffuse pleural mesothelioma suffering from acute dyspnoea and chest pain underwent pericardiocentesis to withdraw pericardial effusion. After some mispunctures blood was withdrawn. Exitus in tabula. At autopsy cardiac tamponade with two cuts of the right ventricle. Pulmonary thrombembolism of the right lung. Advanced diffuse pleural mesothelioma with infiltration of lung, mediastinum, pericard, cuirrassing of left pulmonary artery and descendent aorta thoracica. The connection between iatrogenic cardiac tamponade and death couldn't be established without any doubt in the presence of a concurring cause of death (massive pulmonary thrombembolism). PMID- 2241846 TI - [Performing ability after kidney contusions and kidney ruptures]. AB - 30 casualties who had sustained a kidney contusion (23 patients) or a kidney rupture (7 patients) were questioned about their posttraumatic possibility of action after their recovery. Essential result: Fundamental differences were detected between the two groups. The high degree of the ability to act for a longer period of time may be explained by the comparatively low acuteness of pain after kidney contusions and the impression of most casualties of not being seriously injured. In contrast to kidney contusions, kidney ruptures are generally accompanied by moderate to severe pain. Accordingly, the possibility of action in cases of kidney ruptures is restricted more frequently and to a greater extent than in cases of kidney contusions. The two groups had one thing in common: the casualties' mostly deliberate posttraumatic reaction; there were only 3 patients in a state of helplessness. PMID- 2241847 TI - [Performance following liver, spleen and intestinal ruptures]. AB - In order to extend the knowledge about posttraumatic possibility of action after blunt abdominal traumas, 34 patients mostly having sustained isolated ruptures of the liver, spleen and the intestines, were interviewed after their recovery; the results obtained were separated by the organs involved. Essential result: In general, there is a close correlation between the acuteness of pain, the patient's assessment of severity of the injury and the degree of the ability to act during the first posttraumatic minutes. In the further course of the injury, the capacity to act was limited by the extent and the developmental speed of the loss of blood into the abdominal cavity, provided that it was not limited or cancelled primarily by the acuteness of pain. No correlation could be detected between the extent of rupture and the acuteness of pain. The casualties' thoughtful, deliberate behavior was the predominant posttraumatic characteristic. There was a varying posttraumatic clinical picture ranging from freedom from pain to severe pain and non-restricted possibility of action to the inability to act. PMID- 2241848 TI - [Statistics of blunt abdominal trauma in an autopsy sample at the Institute of Forensic Medicine of the Wurzburg University]. AB - The autopsy material of the Institute for Forensic Medicine of the University of Wuerzburg, comprising 2512 post-mortem examinations between 1981 and 1988, was statistically analyzed. Blunt abdominal traumas could be detected in 424 (= 17%) of the 2512 deceased. Essential results: In 3/4 of the cases a traffic accident was the harmful event, followed by occupational accidents and suicide. In 9 cases the blunt abdominal trauma was caused by resuscitative measures. 96.6% suffered from severe extraabdominal secondary injuries which, in 72% of the cases, occurred as craniocerebral traumas frequently determining the quoad vitam prognosis. In more than 90% death was caused by cranio-cerebral traumas, exsanguination, polytraumas as well as injuries of the cervical spine and the cervical spinal cord. Approx. 2/3 of the casualties died within 1 hour after having sustained the trauma. Only 31 injured persons did survive the harmful event more than 10 days; just 5 of them did not die before a period of more than 30 days. Late death was predominantly caused by secondary injuries adding up, peritonitis, pneumonia or pulmonary embolism. PMID- 2241850 TI - [Electrical impedance and time of death in the animal model]. AB - To study passive electric parameters of the rat skeletal muscles in relation to the time of death, investigations were carried out using the impulse distortion method of Pliquett. This measuring method enables the evaluation of the electric rectangular impulse distorted by the biological tissues, which contains any essential information on the passive electric properties of the object to be measured. The passive electric parameters change in the studied time interval up to 79 h post mortem in a characteristic fashion. The linear correlation of the evaluated impulse parameters at the time of death is closest (r = 0.75) between 0.5-8.5 h post mortem, the scatter of single values in late postmortal periods is in part considerable. A further development of the measuring technique and standardization of the measuring method let the passive electric parameters appear to be appropriate magnitudes for estimating the time of death. PMID- 2241849 TI - [Post-traumatic hydrocephalus--result of repeated abuse of a young child]. AB - Serious physical and psychic abuse of children is a much discussed theme in forensic, juridical and sociological literature. This paper deals with the pitiable case of a meanwhile four years old infant having been battered by his stepmother. At the age of two years the boy was unconscious admitted to the hospital. Computertomography of the brain did not show any pathological findings. Because of multiple effusions of blood of variable age located at the child's body the stepmother was noticed and accused of assault and battery, but the trial ended in acquittal. Two years later the boy suffered from serious neurological symptoms and computertomography showed high-pathological alterations such as hydrocephalus, parietooccipital hygroma and a damage of the brain. PMID- 2241851 TI - [Legal and moral objections to medical research on cadavers and cadaver parts]. AB - The interpretation of Section 190 oStGB by jurisdiction and doctrine makes medicinal research more difficult. In contrary to the ruling legal arguments an responsible scientifically research-work with corpses or parts of corpses cannot realize the facts of the case provided that the comprehension of the related laws are interpreted proper and accurate. PMID- 2241852 TI - [Suicide '87. Suicide statistics of the year 1987 with regard to autopsy and inspection]. AB - The suicides committed during the year 1987 in the catchment of the Institute for Forensic Science at the University of Vienna were analysed in regard to their sexual and seasonal distribution, emphasizing most of all the applied methods. This survey shows impressively the meaning of giving data as complete as possible, especially of including the coroner's inquest among the suicide statistics, which prove to be rather distorted as long as they are only based on post-mortem data. PMID- 2241853 TI - [Effects of "the embryo protection law" on "encapsulated" organ transplantation]. AB - In order to create a capsula-protected homeotransplantat all manipulations which prevent the birth of the child or the growth of other "unwanted" organs will be done either on an egg or on an embryo (in vitro). Both is regarding the current Criminal Law not forbidden. The discussion concerning the Protection of Embryos and the in vitro fertilization in Austria and the Federal Republic of Germany shows, that human semen and eggs should be protected and any artificial variation of them, as well as manipulations on embryos, should be forbidden, even by penal law. If this becomes law in Austria, the capsula-protected homeotransplantation will be incompatible to the abortion allowed until the 3. month of pregnancy ("Fristenlosung"). PMID- 2241854 TI - [Evaluation of results of breath alcohol determination]. AB - Having determined the random errors (Standard deviation) on the Alcomat 9.2 microns, experiments about influences by solvent-exposed persons on measured values are reported and about the determination of runaway-data; average-values of the decrease in breath-alcohol per unit of time are derived by graphs of catabolism after consumption of alcohol. PMID- 2241855 TI - [Screening and detection of nimetazepam and its chief metabolites]. AB - The article describes analytical data for the screening and detection of nimetazepam and its major metabolites. The methods comprise thin-layer chromatography, gas chromatography, UV-spectrophotometry, infrared- and mass spectrometry. PMID- 2241856 TI - [Attempted infanticide with a happy ending. Report of infanticide in Tirol and Vorarlberg]. AB - The paper presents an analysis of infanticides which happened during the last 20 years, investigated by the Institute of Forensic Medicine at the University of Innsbruck. On the basis of some casuistries forensic and criminalistic aspects of infanticides will be discussed. Special attention is payed to two cases of "survived infanticides" with re-establishing of the relationship between mother and child. PMID- 2241857 TI - [Density of immunoreactive cells in the spleen in drug fatalities]. AB - 66 autopsied drug-related death cases in the Institute of Legal Medicine of Cologne of the years 1979 to 1989 were morphologically examined to get information whether cytological investigations of the spleen reveal a damage of the immune system. The weights of the spleen were registered and immunoreactive cells, i.e. macrophages, B- and T-lymphocytes, were quantitative counted. Neither a significant alteration of the weights of the spleen nor an important change of the density of the immunoreactive cells could be registered. PMID- 2241858 TI - [Age determination based on the structure of the proximal parts of the humerus and femur]. AB - Founded on known forensic material a diagram of 7 classes is presented, which allows age determination by means of proximal parts of humerus or femur. The method might be used on direct view of the bones or on x-ray photographs. Therefore it can be employed on the living as well. Factors which might affect the outcome are discussed. PMID- 2241859 TI - [Determining gunshot distance without bullet entry--a new source of error in determining gunshot distance from point of entry]. AB - A court case lead to a quantitative determination of lead and antimony by atomic absorption at distances 10 to 20 cm from the bullet hole. As a surprising result at first the area-concentrations of lead and antimony increased with rising distance from the muzzle and reached a maximum, after that maximum like expected a decrease was found. The phenomena is of general interest because otherwise misinterpretations in chemical determination of gunshot firing distances would be possible. PMID- 2241860 TI - [Medical and technical aspects of the effect of weapons III. Black powder muzzle loading guns]. AB - The report deals generally with ballistics and morphology of wounds caused by black powder muzzle loading guns. Two cases are reported. PMID- 2241861 TI - [Health risk caused by sulfur dioxide]. AB - The short time lasting exposure to SO2 at a level of 1.24 mg/m3 and dust (0.11 mg/m3) means a risk for the health of children, old persons and persons suffering from heart/lung diseases. An increase of asthmatic symptoms is expected. Moreover the risk is raised by inhalation of dust containing sulfates. PMID- 2241862 TI - [Rational control analysis within the scope of a methadone program]. AB - To effectively control a methadone maintenance program a GC-MS-method was developed to simultaneously assay methadone, the opiates including monoacetylmorphine, cocaine and methaqualone. The automation of the GC-MS analysis including the evaluation made possible by suitable operators renders possible a procedure, which is cheaper than the corresponding immunoassays while allowing to differentiate between the opiates without the second step. PMID- 2241863 TI - [Cardioactive contaminants and actual active ingredient content of various digitalis preparations]. AB - To establish possible cardioactive impurities which have not been totally separated while isolating the compound from plant material several preparations containing digoxin (NOVODIGAL = beta-acetyldigoxin, LANITOP = beta-methyldigoxin and LANICOR = digoxin) were analyzed by HPLC-chromatography after careful extraction. Impurities were found (digoxigenin, digoxigenin-monodigitoxosid, digoxigenin-bisdigitoxosid) which on the one hand occur as natural lanatosid derivates in digitalis leaves but on the other hand also are described as possible metabolites of digoxin in human organism. The experiments have shown that the results of studies in metabolization of digoxin without knowledge of purity of the substance applied have to be interpreted with care. PMID- 2241864 TI - [Chemical-toxicologic studies of the epidemiology of drug use (1.)]. AB - During a long term program we secured when possible blood from a femoral vein of dead bodies. Until now 207 cases which were not selected have been investigated. The analyses were performed by high pressure liquid chromatography to prove extractable as well as by gas chromatography to determine volatile substances. These results are represented and correlated with the investigation of the CID or the Department of Public Prosecution respectively and with the results of autopsies if available and discussed. PMID- 2241866 TI - [The role of ozone within the scope of the "Figurella Program"]. AB - The method given by the slimming institute "Figurella International", to lose weight without applying chemistry or dieting, is scrutinized critically. The ozone treatment, one of the compounds of the method, proves to be useless. To overcome the general problem caused by photochemical oxidants the company should be set under pressure to stand back from producing ozone, which proves to be a major air pollutant but not to have any effect on the result of the slimming programme. PMID- 2241865 TI - [Structural changes in the lung in the late stage of fatal paraquat poisoning]. AB - Poisoning with Paraquat, an efficient weedkiller, causes a progressive interstitial fibrosis of the lung starting after about one week's latency. The X ray findings of a 30-year-old female patient who died 12 days after oral ingestion of Paraquat could be documented. We found a correlation between X-ray examination and microscopic post mortem findings of necrotizing alveolitis of the lung changing from exsudative to sclerosing alterations. This diffuse interstitial fibrosis was accompanied by an increase of contractile filament laden cells, characterized by an expression of alpha-smooth muscle actin, which could be identified by immunohistochemical methods. The substantial increase in alpha-actin containing cells has recently been observed in cases of Bleomycin injured lungs. PMID- 2241867 TI - [Autopsy technique and basic legal aspects of autopsy]. AB - Dissection techniques and questions regarding the laws governing autopsy. Autopsy techniques vary. Hamperl's methods, in my opinion, best fulfil the demands of pathology as well as of forensic medicine. In order to obtain more conclusive findings, the dissection of internal organs in several so-called packages, e.g. throat and chest organs and kidneys in the urogenital system, is preferable. Severance of the heart as a means of achieving bloodlessness (Blutleere) should be tolerated only in isolated cases. Some comments on hygienic working methods are in order, not least because of frequent violations in this area. The dignity of the deceased demands hygienic conditions and that the external appearance of the body be reestablished. The removed organs should be returned to the body for burial. Burial should not be used as a means of waste disposal for the institute. The most common and well-known autopsy cases are also dealt with: legal and administrative autopsy. Only forensic autopsy is governed by Para. 87 StPO, albeit incompletely. The definition of the medical examiner is difficult. According to the law on the standardization in Public Health dated 3. 7. 1934 (RGBl. I., p. 531), these tasks should come under the jurisdiction of the health authorities. Since these are not in a position, either from a personnel or material standpoint, to assume these tasks, it is customary, as is the case in the Frankfurt area, for a service contract to be concluded with the director of the institute for forensic medicine. This solution harbours two dangers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2241868 TI - [The natural history of scoliosis]. AB - Adequate treatment of scoliosis requires from the managing doctor a detailed knowledge about the natural history of the disease for correct indication of the various possibilities for treatment and favourable influence of the spontaneous history. Essential prognostic factors of idiopathic scoliotic forms and congenital or neuromuscular scolioses will be demonstrated. PMID- 2241869 TI - [Personal experiences using the Cheneau brace]. AB - Idiopathic scoliosis under 20 degrees were treated by physiotherapeut methods alone. At scoliosis with curves between 20 and 45 degrees a correction by means of Cheneau type orthosis; is additionally used during growing age. The over all results of this combined therapy are good. PMID- 2241870 TI - [Use of the halo-gravitation-extension in preoperative preparation in severe scoliosis]. AB - Severe and fixed scoliosis needs a preoperative extension treatment to attain a good result of correction by spondylodesis. Halo-up-extension is a very simple, comfortable and successful method to prepare patients with a severe scoliosis for operation. From January 1981 to July 1989 we carried out the preoperative halo-up Extension treatment at 45 patients. 39 of them had a severe scoliosis with a cobb angle of more than 70 degrees. The correction by halo-up-Extension runs on an average of 35% of the total correction. PMID- 2241871 TI - [Indications for and results of surgical scoliosis therapy using VDS instrumentation (ventral derotation spondylodesis)]. AB - The complications of 97 patients who were operated with anterior spinal instrumentation were frequent, but insignificant. 22 of these patients with lumbar and thoracolumbar curves in whom the VDS instrumentation was used were reviewed. A 79% correction was obtained in the coronal plane. Loss of correction was 11% in the first year and further 2% at 56 months average follow up. In the sagittal plane a mild tendency to increased kyphosis was found. A permanent "adding on" phenomenon occurred in one case. The VDS-instrumentation appears the apparatus of choice for treatment of thoracolumbar and lumbar scoliosis, other indications are discussed. PMID- 2241872 TI - [Indications for and results of the CD procedure (Cotrel Dubousset) in surgical scoliosis therapy]. AB - At the orthopaedic University Hospitals of Mainz and Munster more than 200 patients were treated surgically according Cotrel and Dubousset procedure. By means of this operation average corrections of the curves of 50.7% to 56.7% could be reached in the first 150 patients, depending of the localisation of the curve. Operative procedure, duration of operation and blood loss are adequate to known procedures. Pre- and postoperative CT's in 24 patients with idiopathic scolioses showed a mean correction of the rotation angle in the apex vertebra of 28.5% in relation to the anterior midline of the body and of 23.8% in relation to the sagittal plane. The best corrections could be observed in lumbar curves and in the lumbar curves of double major scoliosis. A postoperative therapy with cast or braces is not necessary. PMID- 2241873 TI - [Aseptic necrosis of the lunate bone. Etiology, clinical aspects, stage-adjusted therapy]. AB - The development of the aseptic necrosis of the lunate bone is so far not fully understood. Therapeutical problems result from the very late discovery of the disease and from the central position in the carpal bone system. Bad long-term results come out of therapies not able to revitalize the lunate bone. Therefore the therapeutical goal attempted must be to keep the structures of the bone alive and to avoid major pathological changes of the whole carpal bone system. More or less good results could be shown for these patients with a total break-down of the lunate bone treated with the intercarpal-arthrodesis described by Graner. PMID- 2241874 TI - [Graner's intercarpal arthrodesis as therapy of aseptic lunate bone necrosis]. AB - From 1978 till 1989 at the Department of Orthopaedics (University of Graz, Faculty of Medicine, Division of Surgery) 25 patients were operated for the reason of an avascular necrosis of the lunate bone when the bone structures were already destroyed. The form of therapy was the intercarpal-arthrodesis, developed by Orlando Graner 1966, in a slightly modified way. On the one hand through creating an intercarpal block it is possible to create more or less plain sides of the radiocarpal joint and on the other hand one can stop the carpal collapse what explains long-term-results rather acceptable. The most important disadvantage of this form of therapy is the often found loss of range of movement in the operated radiocarpal joint. PMID- 2241875 TI - [Tissue preservation in the DRG]. AB - The conservation of tissue in GDR is an example system of superregional supply with tissue transplants, which was established with the foundation of the Central Tissue Bank at the Charite in 1956 e. g. with the following arrangement of tissue banks in Leipzig and Rostock in 1966 and 1969. The concept of this tissue banks is characterized by means of decentralised production of tissue material under conditions of section and the central preparation, conservation and storage (chemical or radiation sterilization, conservation on base of freeze-drying (or freeze-storage), aseptic packing and storage by room temperature). This system allows the consistent disposal of 30 various nonvital tissue preparations. Until 1989 more than 170,000 allogeneic and xenogeneic tissue transplants have been produced in the tissue banks of country of which nearly 130,000 were used in 300 clinics. PMID- 2241876 TI - [The development of the assortment and requirements of the tissue bank of the District Institute for Blood Donation and Transfusion Leipzig]. AB - Since the foundation of the tissue bank at the District Institute for Blood Donation--and Transfusion Service of Leipzig in 1966 the range of production and the assortment of nonvital tissue transplants has considerably increased. The amount of clinical establishments and their requirements is considerably increased, in which the realization of demands is not always possible without waiting periods. The main tissue conservation method is the cryo-drying. Besides the extreme cooling and cryo-preservation were used. Problems of transportation of cooled tissue conserves were discussed. PMID- 2241878 TI - [Regeneration of bone following thermal injury]. AB - In an animal experiment we could prove, that a spontaneous regeneration of periosteum on thermally injured bone is not to be seen within three month, when the bone is covered by soft tissue only. Using a periosteal flap to cover a burned bone, regeneration could be observed from the endosteum and the periosteum alike. After making the bone with a fluorescent labels, paths and velocity of bony regeneration could be defined. PMID- 2241877 TI - [Bone replacement using demineralized allogeneic bone in animal experiments]. AB - The implantation of bone matrix in muscle bag or trepanation defects of rats with greatest reproducibility will induce osteogenesis and defect healing. The phenomenon of osteo-induction was possible to obtain only in first steps in higher developed mammals. Investigations in nude rats have shown a clear difference in biologic reaction on the matrix of various species. The osteo regeneration in replacement weak defect of ulnar bone in dogs showed a massive greater reactivity of autogenous spongiosa, whereas bank spongiosa and bone matrix produced not more new bone as the control. An increase of osteoinductive matrix potency is a supposition for practical use in case of severe bone defects. PMID- 2241879 TI - [Application possibilities of human bone-collagen substance as a transplant in skeletal surgery]. AB - We present first results of our clinical trial with a demineralized-bone-matrix (DBM) not only as a transplant to fill up a defect of bone but above all to induce local osteogenesis. Indications and practical applications of the material of transplants are described. By help of the clinical progresses and the reports of laboratory examinations the biological compatibility is regarded in this paper. Roentgen morphologically fine structures of the transplants and their transplant beds are described in serial roentgenography and used as evaluation of processes of transformation and building in of bones. The in a relative good time appearing markings of trajectories of the fine structures in the sphere of the transplant as a sign of accelerated regeneration of "organic bony substance" allows the expectation on being released osteogenetic potencies by DBM for the induction of local bone regeneration. PMID- 2241881 TI - [The use of homologous spongiosa chips in the treatment of juvenile bone cysts]. AB - Juvenile bone cysts are characterized by trials of hypothetic interpretations in case of aetiology and general disagreement in relation to indicated therapy. The therapeutic spectrum is ranging from primary conservative treatment till subtotal e.g. total cyst resections. Because in juveniles a quantitative limitation for gathering of autogenous material exists the use of allogenous cancellous bone chips has a definitive place in treatment strategy. PMID- 2241880 TI - [Clinical study on the application of demineralized bone matrix (DBM) in surgical orthodontics]. AB - Demineralized bone matrix has been tested in a clinical study concerning the filling of bone defects in the surgical stomatology. It is reported on the clinical results and the X-ray evaluation of the replacement of bones by demineralized bone matrix. Fifty two implantations in the maxilla and mandible of 51 patients were carried out to be able to evaluate the efficacy of demineralized bone matrix. PMID- 2241882 TI - [Long-term results following acetabuloplasty using cortico-spongiosa banked chips in hip dysplasia and dislocation]. AB - Analysed are altogether 119 acetabuloplasties correcting acetabular fossae using corticospongiose bankchips. The operations of the years from 1975-1983 have been used for this analysis. Examined are by clinical progress and serial roentgenography the compatibility, the resistance to mechanical stress as well as building in and transformation of the corticospongiose bankchips. Finally is determined the progress of the socket by using the socket-roof- and centre-corner angle postoperative on an average of 10 years. PMID- 2241883 TI - [Autogeneic and allogeneic bone tissue transplantation in the profession of orthopedics]. AB - In the time between 1981 to 1987 about 9,190 operations had been performed at the Orthopaedic Department of the Humboldt University Charite Berlin. In 1592 cases (= 17.3%) we transplanted autogeneic or allogeneic bone tissues. We report about the kind and selection of transplanted bone tissue with respect to availability and target function. PMID- 2241884 TI - [Methods for the preservation of soft tissue preparations for clinical use]. AB - The demand for consistent supply of nonvital allogenous implants in tissue banks has the supposition for graft preservation. Besides of many logistic advantages the preservation methods are accompanied by the influence of original attributes, especially of biomechanic parameters in soft tissue preparations. A procedure of dura mater preparation, of fascia lata, tendons and skin is demonstrated which is preserving the required qualities of plasticity, softness and resistance. Biomechanic comparative investigations of other preservation procedures are done and first clinical results are demonstrated. PMID- 2241885 TI - [The effect of respiratory activity on the QRS complex in the ECG in clinically healthy horses and horses with chronic lung diseases]. AB - Interrelations between respiration and changes in amplitudes of the QRS-complex of the ECG of horses were investigated. The value of the R-vector and both its components Rx and Ry decrease during inspiration and increase in the expiration phase. It means, that the R-waves in leads from cranial to caudal (y, II, aVF) and from right to left (I) become smaller with inspiration and larger with expiration. The difference of the amplitudes may be important, especially in horses with respiratory problems, so that it has to be noted when evaluating electrocardiograms. For that purpose it is not necessary to draw respiratory curves. It is proposed to evaluate the heart-cycle with the largest R-wave (expiration) only when there are differences in the R-amplitudes. Pulmonary air content is discussed as a possible cause. PMID- 2241886 TI - [Lip-jaw split in a calf. Comments on the article, "Cornea dermoids and double malformations of the nares in a calf," by C. Neophytou]. AB - A case of Cheilognathoschisis in a bull calf is demonstrated. The author supposes, that the malformation, which Neophytou reported, was a cheilognathoschisis too. PMID- 2241887 TI - [Comparison of the effect of an alfaprostol-oxytocin combination and of carbamylcholine alone for the prevention of intrapartum mortality of piglets with regard to the body condition of the sow]. AB - In a single large pig production unit of 6,000 breeding sows, 3 Groups of 100 sows each were formed at random on the 110th day of pregnancy. Each Group was evaluated and divided according to body condition in three subgroups. The Groups were treated as follows: Group 1: received on the 113th day of pregnancy a 3 mg single intramuscular dose of Alfaprostol, 24 hours later a single intramuscular dose of 10 i.U. of Oxytocin. Group 2: received on the 113th day of pregnancy a 0.2 mg single intramuscular dose of Carbamylcholin. Group 3: received a 3 ml intramuscular dose of physiologic NaCl solution on the 113th day of pregnancy. The parameter "intrapartal dead piglets" was evaluated. Group 1 and 2, especially in Subgroups KK3, showed significant less intrapartal death when compared to Group 3. PMID- 2241888 TI - [The pathogenicity of Campylobacter jejuni as a monoinfection and as a mixed infection with Escherichia coli 078:K80 in broilers]. AB - Two week old broilers (n = 61) with a monoinfection with Campylobacter jejuni (0.5 ml of suspension containing 10(5) CFU/ml per os) showed reduced increase in weight during week 3 after infection compared to the control group. An other group of chickens (n = 31) was additionally infected with a suspension of Escherichia (E.) coli O78:K80 via drinking water from day 4 to 6 after the primary infection. This mixed infection provoked clinical signs of a disease and reduced increase in weight during the first two weeks of the experiment. Seven broilers of this group showed a fibrinous pericarditis and/or perihepatitis. Four of these chickens died. It can be concluded from the experiment that an infection with Campylobacter causes reduced weight gain and supports a systemic infection with E. coli. PMID- 2241889 TI - [Use of bacteriological techniques in the quality control of poultry slaughtering]. AB - Factors influencing the bacteriological status of materials, treated on a special stage of processing, can be detected by analysis of the flow of production. Changing the design of equipment, change of the production flow and education of the personnel who is handling the equipment can eliminate or minimize the risks. The data are to be collected on the basis of the special conditions of the plant. The daily checks can be performed by visual inspection or by using physical techniques. PMID- 2241890 TI - [Osteosynthesis today]. AB - Modern osteosynthesis has remarkably changed the fracture treatment in small animals with its aim to re-establish full limb function. The scientific basis is elaborated and the different surgical methods are clinically proved. Veterinarians who want to perform operative fracture treatment must have sufficient training in the different techniques, the possibility to perform aseptic surgery and suitable instruments and implants. As this type of surgery means severe stress to the trauma patient, surgery cannot be done before his condition is stabilized. PMID- 2241891 TI - Ultraviolet B radiation induction of ornithine decarboxylase gene expression in mouse epidermis. AB - The cellular effects of u.v. radiation have been studied by using a hairless mouse model in vivo. U.v. B radiation (u.v.B) induced the activity of the enzyme ornithine decarboxylase (ODC) in mouse epidermis. Maximal induction was noted after radiation with 90 mJ/cm2, and increased ODC activity was first detected 2 h after u.v.B exposure. U.v.B. also induced the expression of the ODC gene in a time- and dose-dependent manner, but did not induce the levels of actin mRNA transcripts. Cycloheximide treatment did not alter basal levels of ODC mRNA transcripts and had no effect on the u.v.B induction of ODC-gene expression. The results of these experiments demonstrate that u.v.B radiation induces both the expression of the ODC gene and the activity of the enzyme, and provides a useful 'in vivo' paradigm for the analysis of the molecular effects of u.v.B radiation. PMID- 2241892 TI - Structure of the human sialophorin (CD43) gene. Identification of features atypical of genes encoding integral membrane proteins. AB - A human sialophorin (CD43) specific genomic clone was isolated, and a 6.5 kb fragment containing the 4.6 kb sialophorin gene was sequenced. The promoter region contains no TATA or CAAT boxes, but is highly enriched in G and C nucleotides and contains short repeat sequences similar to those found in the promoters of 'housekeeping' genes. S1-nuclease protection and primer-extension experiments established that the sialophorin gene has two major transcription initiation sites. There is a single intron of 378 bp that interrupts the sequence specifying the mRNA 5' untranslated region. The gene is therefore unusual in that the discrete extracellular, transmembrane and intracellular regions of the protein, including repeat sequences in the extracellular region, are not encoded by separate exons. Utilization of alternative polyadenylation signals was previously shown to generate two sialophorin mRNAs of 1.9 and 4.3 kb, which differ in the length of their 3' untranslated regions. Sequence analysis of the gene establishes that a single polyadenylation signal 2301 bp downstream of the first major transcription initiation site and five overlapping polyadenylation signals beginning a further 2290 bp downstream define the 3' termini of the 1.9 and 4.3 kb mRNA species respectively. The gene contains potential Z-DNA structures, Aly sequences, and elements that may be involved in regulating mRNA stability. PMID- 2241893 TI - Solubilization and purification of a membrane-associated 3,3',5-tri-iodo-L thyronine-binding protein from rat erythrocytes. AB - 3,3',5-Tri-iodo-L-thyronine (L-T3) binding sites from rat erythrocyte membranes were solubilized in an active form by using the zwitterionic detergent CHAPS or the anionic detergent lauroylsarcosine. The binding protein was successively purified by Sephadex G-200 and affinity chromatography. The purified material retained its binding activity and exhibited high affinity and specificity compared with those displayed in the original membrane. Yield was about 10% of the starting activity. The specific binding activity was enriched by approx. 100 fold, which represents a purity of only 0.1%. Analysis of the purified preparation on SDS/PAGE showed two major protein bands (Mr 64,000 and Mr 50,000), but these could not represent the binding protein since the purity obtained was low. However, affinity-labelling experiments with N-bromoacetyl-L-[125I]T3 in intact membranes showed that two proteins (also with Mr values of 64,000 and 50,000) bound the hormone specifically, suggesting a co-migration of hormone receptors and contaminants on gel electrophoresis. PMID- 2241894 TI - Purification of two distinct proteins of approximate Mr 80,000 from human epithelial cells and identification as proper substrates for protein kinase C. AB - A Mr-80,000 acidic phosphoprotein ('80K protein') is a specific substrate for protein kinase C. We attempted to purify the 80K protein from a human squamous cell carcinoma cell line, Ca9-22, by the sequential use of heat treatment, (NH4)2SO4 precipitation, Mono Q column chromatography, proRPC column chromatography and gel filtration. The 80K protein was assayed by phosphorylation in vitro by using partially purified human type III protein kinase C, and was fractionated into two distinct molecular species with slightly different Mr values, designated 80K-L and 80K-H proteins. Phosphorylation occurred mainly at serine residues of these proteins. Two-dimensional phosphopeptide maps after trypsin digestion and kinetic profiles of phosphorylation were different from each other. Ca2(+)- and phospholipid-dependency of the phosphorylation in vitro confirmed that both 80K-L and 80K-H proteins are true substrates for three subtypes of protein kinase C. The 80K-L protein was a preferential substrate for type III protein kinase C, and the 80K-H protein was phosphorylated more effectively by type I and type II protein kinase C. The possible roles of these two distinct 80K proteins in signal transduction are discussed. PMID- 2241895 TI - Characterization of a high-affinity membrane-associated ornithine decarboxylase from the free-living nematode Caenorhabditis elegans. AB - Ornithine decarboxylase has been identified and characterized in the free-living nematode Caenorhabditis elegans. Unlike previously described ornithine decarboxylases, the enzyme activity is membrane-associated and remains in the membrane fraction after treatment with high salt, detergents or phosphatidylinositol-specific phospholipase C. Ornithine has an apparent Km value of 2.7 microM for ornithine decarboxylase. The enzyme is competitively inhibited by arginine and lysine with Ki values of 4.0 and 24.4 microM respectively. None of the other naturally occurring amino acids inhibited more than 10% of the enzyme activity at concentrations up to 1 mM. Agmatine, putrescine, spermidine and spermine inhibit ornithine decarboxylase in a non-competitive manner with Ki values of 10, 53.5, 59 and 855 microM respectively. A similar ornithine decarboxylase activity was also identified in membrane preparations from the parasitic nematode Haemonchus contortus. PMID- 2241897 TI - High specific induction of spermidine/spermine N1-acetyltransferase in a human large cell lung carcinoma. AB - The cytotoxic response of the human large cell lung carcinoma line NCI H157 to exposure to the polyamine analogue N1 N12-bis(ethyl)spermine (BESpm) is preceded by an extremely high induction of spermidine/spermine N1-acetyltransferase (SSAT). The human enzyme has now been purified greater than 300-fold to apparent homogeneity and found to cross-react with antisera raised against rat liver SSAT. Although other acetylases are capable of acetylating polyamines using acetyl-CoA as the acetyl donor, the greater than 600-fold induction within 24 h was found to be specifically SSAT, since essentially all activity was precipitable by the specific antisera. The human enzyme appears to be similar to the rat enzyme in subunit size under reducing conditions (approximately 20 kDa), substrate specificity and kinetic parameters. Preliminary results using actinomycin D and cycloheximide suggested that the unusually high induction by N1 N12 bis(ethyl)spermine in the human lung cancer line result from new mRNA and protein synthesis. This hypothesis is further substantiated here by 'in vitro' translation experiments comparing poly(A) mRNA from control and treated cells. The large cell lung carcinoma line NCI H157 represents a useful system to produce large amounts of the SSAT protein and to study the molecular events responsible for the induction and control of this important polyamine-metabolic enzyme. By using this rich source of SSAT protein, a partial amino acid sequence was determined by N-terminal sequencing of endoproteinase Lys-C digestion fragments. Further, this system should be useful in determining whether there is an association between the unusually high induction of the acetylase and the observed cytotoxicity in the NCI H157 cells. PMID- 2241896 TI - 5'-S-(2-aminoethyl)-N6-(4-nitrobenzyl)-5'-thioadenosine (SAENTA), a novel ligand with high affinity for polypeptides associated with nucleoside transport. Partial purification of the nitrobenzylthioinosine-binding protein of pig erythrocytes by affinity chromatography. AB - Derivatives of N6-(4-aminobenzyl)adenosine (substituted at the aminobenzyl group) and 5'-linked derivatives of N6-(4-nitrobenzyl)adenosine (NBAdo) were evaluated as inhibitors of site-specific binding of [3H]nitrobenzylthioinosine (NBMPR) to pig erythrocyte membranes. Potent inhibitors were SAENTA [5'-S-(2-aminoethyl)-N6 (4-nitrobenzyl)-5'-thioadenosine] and acetyl-SAENTA (the 2-acetamidoethyl derivative of SAENTA). SAENTA was coupled to derivatized agarose-gel beads (Affi Gel 10) to form an affinity matrix for chromatographic purification of NBMPR binding polypeptides, which in pig erythrocytes are part of, or are associated with, the equilibrative nucleoside transporter. When pig erythrocyte membranes were solubilized with octyl glucoside (n-octyl beta-D-glucopyranoside) and applied to SAENTA-Affi-Gel 10 (SAENTA-AG10), polypeptides that migrated as a broad band on SDS/PAGE with an apparent molecular mass of 58-60 kDa were selectively retained by the affinity gel. These polypeptides were identified as components of the nucleoside transporter of pig erythrocytes by reactivity with a monoclonal antibody (mAb 11C4) that recognizes the NBMPR-binding protein of pig erythrocytes. Retention of the immunoreactive polypeptides by SAENTA-AG10 was blocked by NBAdo. The immunoreactive polypeptides were released from SAENTA-AG10 by elution under denaturing conditions with 1% SDS or by elution with detergent solutions containing competitive ligands (NBAdo or NBMPR). A 72-fold enrichment of the immunoreactive polypeptides was achieved by a single passage of solubilized, protein-depleted membranes through a column of SAENTA-AG10, followed by elution with detergent solutions containing NBAdo. These results demonstrate that polypeptide components of NBMPR-sensitive nucleoside-transport systems may be partly purified by affinity chromatography using gel media bearing SAENTA groups. PMID- 2241898 TI - Hydrogen-bonding in enzyme catalysis. Fourier-transform infrared detection of ground-state electronic strain in acyl-chymotrypsins and analysis of the kinetic consequences. AB - I.r. difference spectra are presented for 3-(indol-3-yl)acryloyl-, cinnamoyl-, 3 (5-methylthien-2-yl)acryloyl-, dehydrocinnamoyl- and dihydrocinnamoyl chymotrypsins at low pH, where the acyl-enzymes are catalytically inactive. At least two absorption bands are seen in each case in the ester carbonyl stretching region of the spectrum. Cinnamoyl-chymotrypsin substituted at the carbonyl carbon atom with 13C was prepared. A difference spectrum in which 13C-substituted acyl enzyme was subtracted from [12C]acyl-enzyme shows two bands in the ester carbonyl region and thus confirms the assignment of the features to the single ester carbonyl group. The frequencies of the ester carbonyl bands are interpreted in terms of differential hydrogen-bonding. In each case a lower-frequency relatively narrow band is assigned to a productive potentially reactive binding mode in which the carbonyl oxygen atom is inserted in the oxyanion hole of the enzyme active centre. The higher-frequency band, which is broader, is assigned to a non productive binding mode in each case, where a water molecule bridges from the carbonyl oxygen atom to His-57; this mode is equivalent to the crystallographically determined structure of 3-(indol-3-yl)acryloyl-chymotrypsin, i.e. the Henderson structure. A difference spectrum of dihydrocinnamoyl chymotrypsin taken at higher pH shows resolution of a feature centred upon 1731 cm-1, which is assigned to a non-bonded conformer in which the carbonyl oxygen atom is not hydrogen-bonded. Perturbation of the protein spectrum in the presence of acyl groups is interpreted in terms of enhanced structural rigidity. It is reported that the ester carbonyl region of the difference spectrum of cinnamoyl subtilisin is complicated by overlap of features that arise from protein perturbation. Measurements of carbonyl absorption frequencies in a number of solvents of the methyl esters of the acyl groups used to make acyl-enzymes have permitted determination of the apparent dielectric constants experienced by carbonyl groups in the enzyme active centre as well as a discussion of the effects of polarity. The ester carbonyl bond strengths of the various conformations were estimated by using simple harmonic oscillator theory and an empirical relation between the force constants and bond strengths. The fractional bond breaking induced by hydrogen-bonding was used to calculate rate enhancement factors by using absolute reaction rate theory.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2241899 TI - The amino acid sequence of cytosolic aspartate aminotransferase from human liver. AB - 1. The cytosolic aspartate aminotransferase was purified from human liver. 2. The isoenzyme contains four cysteine residues, only one of which reacts with 5,5' dithiobis-(2-nitrobenzoic acid) in the absence of denaturing agents. 3. The amino acid sequence of the isoenzyme is reported, as determined from peptides produced by digestion with trypsin and with CNBr, and from sub-digestion of some of these peptides with Staphylococcus aureus V8 proteinase. 4. The isoenzyme shares 48% identity of amino acid sequence with the mitochondrial form from human heart. 5. Comparisons of the amino acid sequences of all known mammalian cytosolic aspartate aminotransferases and of the same set of mitochondrial isoenzymes are reported. The results indicate that the cytosolic isoenzymes have evolved at about 1.3 times the rate of the mitochondrial forms. 6. The time elapsed since the cytosolic and mitochondrial isoenzymes diverged from a common ancestral protein is estimated to be 860 x 10(6) years. 7. Experimental details and confirmatory data for the results presented here are given in a supplementary paper that has been deposited as a Supplementary Publication SUP 50158 (25 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1990) 265, 5. PMID- 2241901 TI - Studies on the origin of biliary phospholipid. Effect of dehydrocholic acid and cholic acid infusions on hepatic and biliary phospholipids. AB - The correlation between the secretion of biliary phospholipid (PL) and bile acid suggests a regulatory effect of bile acid on PL secretion. Bile acids may influence PL synthesis and/or the mobilization of a preformed PL pool. The objective of this study was to determine the contribution of these two sources to biliary PL, by using an experimental protocol in which dehydrocholic acid (DHCA) and cholic acid (CA) were infused to manipulate biliary PL secretion. In control rats, there was a steady state in bile flow. PL secretion and the biliary secretion of newly synthesized phosphatidylcholine (PC). The specific radioactivity of PC in bile was significantly higher than in plasma, microsomes and canalicular membranes. DHCA infusion decreased biliary PC secretion rate by 80%, and secretion returned to normal values at the transport maximum of CA. The specific radioactivity of biliary PC was decreased by 30% by DHCA infusion and reached normal values during CA infusion. There were no significant changes in the specific radioactivity of PC in plasma or cellular organelles during infusion of bile acids. These data indicate that: (1) newly synthesized PC contributes a small percentage to biliary PC; thus a preformed pool (microsomal and extrahepatic) is a major source of biliary PL; (2) the contribution of the extrahepatic pool to the biliary PL may be more important than the microsomal pool. PMID- 2241900 TI - Differential down-regulation of protein kinase C selectively affects IgE dependent exocytosis and inositol trisphosphate formation. AB - Short-term treatment of rat basophilic leukaemia (RBL-2H3) cells with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) activates protein kinase C (PKC) and results in the inhibition of the IgE-dependent formation of inositol phosphates, but in the potentiation of serotonin secretion. Long-term treatment with TPA, which depletes the cells of their endogenous PKC, eliminates both Ca2(+)-ionophore- and TPA- as well as IgE-dependent secretion, but it potentiates by 1.7-fold IgE-induced inositol phosphate formation. Taken together, these observations strongly suggest that the dual actions of TPA on IgE-dependent responses are both mediated by PKC. The opposing effects of TPA are differentially down-regulated. Following TPA treatment, the rate by which the cells lose their ability to undergo exocytosis is faster than the rate at which inhibition of inositol phosphates formation is relieved and their production potentiated. In addition, both processes show different sensitivities to inhibitors of PKC action. Whereas IgE-dependent secretion is completely blocked by the PKC inhibitors K252a, H-7 and sphingosine [concns. causing 50% inhibition (IC50 values) = 25 ng/ml 80 microns and 30 microns respectively], these inhibitors do not relieve inhibition of inositol phosphate formation by TPA, nor do they potentiate this response. These results may imply that the bidirectional control exerted by PKC on IgE-dependent responses is mediated by its different isoenzymes. PMID- 2241902 TI - Expression of human liver arginase in Escherichia coli. Purification and properties of the product. AB - Arginase is an enzyme that catalyses the hydrolysis of arginine to urea and ornithine. It is abundantly present in the liver of ureotelic animals (i.e. those whose excretion is characterized by the excretion of uric acid as the chief end product of nitrogen metabolism), but its purification has hitherto not been simple, and the yield not high. Starting with a partially truncated cDNA for human liver arginase recently made available, we constructed an expression plasmid that had tandemly linked tac promotors placed upstream of a full-length cDNA. By selecting Escherichia coli strain KY1436 as the host micro-organism, we established an efficient system for the production of human liver arginase protein. Chromatographies on CM-Sephadex G-150, DEAE-cellulose and Sephadex G 150, followed by preparative agar-gel electrophoresis, yielded 10 mg of apparently homogeneous enzyme protein from 1 g (wet wt.) of E. coli cells. E. coli-expressed human liver arginase had chemical, immunological and most catalytic properties indistinguishable from those of purified human erythrocyte arginase. However, E. coli-expressed arginase was a monomer of Mr 35,000, whereas the purified erythrocyte arginase was trimer of Mr 105,000. They differed also in pH- and temperature-stabilities. Gel-filtration experiments with these two purified arginases under various conditions, as well as with unfractionated human liver and erythrocyte cytosol preparations, indicated that the native form of human arginase should be of Mr 35,000, and that the trimeric appearance of human erythrocyte arginase after purification was an artifact of the purification procedures. It was thus concluded that, in Nature, the liver and erythrocyte arginases are identical proteins. PMID- 2241903 TI - The use of polyacrylamide-gel electrophoresis for the high-resolution separation of reducing saccharides labelled with the fluorophore 8-aminonaphthalene-1,3,6 trisulphonic acid. Detection of picomolar quantities by an imaging system based on a cooled charge-coupled device. AB - Various monosaccharides, oligosaccharides and small polysaccharides were labelled covalently at their reducing end groups with the fluorophore 8-aminonaphthalene 1,3,6-trisulphonic acid (ANTS), and the resulting fluorescent derivatives were separated by high-resolution PAGE. The electrophoretic mobilities of the labelled saccharides are related largely to the compounds' Mr values, but they are also influenced by the individual chemical structures of the saccharides. Various positional isomers and some epimers, for instance galactose and glucose, were resolved. Oligosaccharide and small polysaccharide derivatives, prepared from an enzymic digest of starch, each differing in size by a single hexose residue and with a range of degrees of polymerization from 2 to 26, were all resolved in a single gel. The method was relatively rapid and simple to perform. It enabled multiple samples to be analysed in parallel with high sensitivity. The fluorescent-labelling procedure was virtually quantitative. As little as 1 pmol of ANTS-labelled saccharide was detected photographically when the gels were illuminated by u.v. light. When the gels were viewed using an imaging system based on a cooled charge-coupled device, as little as 0.2 pmol was detected. The method may be useful for the structural analysis of the carbohydrate moieties of glycoconjugates and other naturally occurring oligosaccharides. PMID- 2241904 TI - Purification and characterization of rat liver minoxidil sulphotransferase. AB - Minoxidil (Mx), a pyrimidine N-oxide, is used therapeutically as an antihypertensive agent and to induce hair growth in patients with male pattern baldness. Mx NO-sulphate has been implicated as the agent active in producing these effects. This paper describes the purification of a unique sulphotransferase (ST) from rat liver cytosol that is capable of catalysing the sulphation of Mx. By using DEAE-Sepharose CL-6B chromatography, hydroxyapatite chromatography and ATP-agarose affinity chromatography, Mx-ST activity was purified 240-fold compared with the activity in cytosol. The purified enzyme was also capable of sulphating p-nitrophenol (PNP) at low concentrations (less than 10 microM). Mx-ST was purified to homogeneity, as evaluated by SDS/PAGE and reverse-phase h.p.l.c. The active form of the enzyme had a molecular mass of 66,000-68,000 Da as estimated by gel exclusion chromatography and a subunit molecular mass of 35,000 Da. The apparent Km values for Mx, 3'-phosphoadenosine 5'-phosphosulphate and PNP were 625 microM, 5.0 microM and 0.5 microM respectively. However, PNP displayed potent substrate inhibition at concentrations above 1.2 microM. Antibodies raised in rabbits to the pure enzyme detected a single band in rat liver cytosol with a subunit molecular mass of 35,000 Da, as determined by immunoblotting. The anti-(rat Mx-ST) antibodies also reacted with the phenol-sulphating form of human liver phenol sulphotransferase, suggesting some structural similarity between these proteins. PMID- 2241906 TI - Inhibitors of phospholipase A2 block the stimulation of protein synthesis by insulin in L6 myoblasts. AB - Insulin at a concentration close to the physiological range (100 mu-units/ml) stimulated protein synthesis in L6 myoblasts by 17%. Pre-treatment with the phospholipase A2 inhibitors mepacrine or dexamethasone prevented this stimulation and decreased the release of prostaglandin F2 alpha, implicating the action of phospholipase A2 and the subsequent metabolism of arachidonic acid to prostaglandins in the stimulation of protein synthesis by physiological doses of insulin. Higher concentrations of insulin (500-1000 mu-units/ml) stimulated protein synthesis in the presence of mepacrine or dexamethasone, suggesting that an alternative pathway may become important in insulin action when phospholipase A2 is inhibited. PMID- 2241905 TI - Two cytochrome P-450 isoforms catalysing O-de-ethylation of ethoxycoumarin and ethoxyresorufin in higher plants. AB - The O-dealkylating activities of 7-ethoxycoumarin O-de-ethylase (ECOD) and 7 ethoxyresorufin O-de-ethylase (EROD) have been fluorimetrically detected in microsomes prepared from manganese-induced Jerusalem artichoke tubers. Cytochrome P-450 dependence of the reactions was demonstrated by light-reversed CO inhibition, NADPH-dependence, NADH-NADPH synergism and by use of specific inhibitors: antibodies to NADPH-cytochrome P-450 reductase, mechanism-based inactivators and tetcyclasis. Apparent Km values of 161 microM for 7 ethoxycoumarin and 0.4 microM for 7-ethoxyresorufin were determined. O-De ethylase activity was also detected in microsomes prepared from several other plant species, including wheat, maize, tulip, avocado and Vicia. ECOD and EROD were low or undetectable in uninduced plant tissues, and both activities were stimulated by wounding or by chemical inducers. Two distinct cytochrome P-450 isoforms are involved in ECOD and EROD activities since (1) they showed different distributions among plant species; (2) they showed contrasting inhibition and induction patterns; and (3) ECOD but not EROD activity was supported by cumene hydroperoxide. PMID- 2241907 TI - Interaction of egg-white glycoproteins and their oligosaccharides with the monomer and the hexamer of chicken liver lectin. A multivalent oligosaccharide combining site exists within the carbohydrate-recognition domain. AB - Binding of egg-white glycoproteins and their oligosaccharides to hexameric solubilized form of the chicken hepatic lectin and the monomeric soluble fragment containing the carbohydrate-recognition domain has been investigated by several techniques. Ligand blotting revealed significant differences in binding to two forms of the lectin only for glycoproteins bearing multiple N-linked oligosaccharide moieties in their molecule (riboflavin-binding glycoprotein, avidin or ovomucoid). Inhibition studies indicated that inhibitory potency in a series of linear and branched N-acetyl-D-glucosamine-terminated oligosaccharides is critically dependent on the number and spatial arrangement of the terminal monosaccharide residues for both forms of the lectin. Direct binding of 4 hydroxyphenyl-derivatized radioiodinated oligosaccharides measured by equilibrium dialysis and frontal affinity chromatography points to the existence of two N acetyl-D-glucosamine-combining sites per one subunit of the lectin, as has been recently reported for the rabbit and rat liver lectin [Lee & Lee (1988) Biochem. Biophys. Res. Commun. 155, 1444-1452]. Highly branch (penta-antennary) oligosaccharides interact with more than one subunit of the hexameric form of the lectin and thus resemble the more complex interaction of the whole glycoprotein. PMID- 2241908 TI - Chemical mechanism of lysophosphatidylcholine: lysophosphatidylcholine acyltransferase from rabbit lung. pH-dependence of kinetic parameters. AB - Lysophosphatidylcholine: lysophosphatidylcholine acyltransferase is an enzyme that catalyses two reactions: hydrolysis of lysophosphatidylcholine and transacylation between two molecules of lysophosphatidylcholine to give disaturated phosphatidylcholine. Following the kinetic model previously proposed for this enzyme [Martin, Perez-Gil, Acebal & Arche (1990) Biochem. J. 266, 47 53], the values of essential pK values in free enzyme and substrate-enzyme complexes have now been determined. The chemical mechanism of catalysis was dependent on the deprotonation of a histidine residue with pK about 5.7. This result was supported by the perturbation of pK values by addition of organic solvent. Very high and exothermic enthalpy of ionization was measured, indicating that a conformational re-arrangement in the enzyme accompanies the ionization of the essential histidine residue. These results, as well as the results from previous studies, enabled the proposal of a chemical mechanism for the enzymic reactions catalysed by lysophosphatidylcholine: lysophosphatidylcholine acyltransferase from rabbit lung. PMID- 2241909 TI - Modulation of mannose receptor activity by proteolysis. AB - Macrophages express a receptor on the cell surface that functions to clear glycoproteins from the extracellular milieu. The activity of this receptor is sensitive to treatment with trypsin. In inflammatory situations, macrophages are activated and exposed to increased levels of extracellular proteases. Under these conditions, mannose receptor activity on the macrophages is diminished. We therefore decided to study the effects of trypsin treatment on the structure and activity of cell-associated and purified receptor that might contribute to the activation-associated receptor down-regulation. Trypsin treatment (1 microgram/ml for 3 h) resulted in the production of a 140 kDa, trypsin-resistant fragment from both intact cells and isolated receptor. This fragment was no longer able to bind ligand. The remaining 35 kDa fragment apparently is further degraded into smaller fragments, since no evidence of this domain was found on Coomassie Blue-stained gels. The 140 kDa fragment retained immunoreactivity and contained at least a portion of the iodinated tyrosine residues following surface labelling with Na125I. Neither calcium nor ligand protected the receptor from proteolysis. In addition, prior treatment with oxidants did not increase the susceptibility of the receptor to trypsin digestion. We conclude from these results that the macrophage mannose receptor is clipped by the serine protease trypsin at the cell surface, resulting in the release and further degradation of the binding domain, and the production of a membrane-associated 140 kDa fragment. This trypsin mediated down-regulation of receptor activity might be important in controlling glycoprotein clearance during inflammation. PMID- 2241910 TI - Insulin resistance of hind-limb tissues in vivo in lactating sheep. AB - 1. The effects of varying the plasma insulin concentration by infusion while maintaining euglycaemia by infusion of glucose on nutrient arterio-venous differences across the hind-limb and mammary gland in lactating and non-lactating sheep were investigated. 2. Insulin infusion increased the glucose arterio-venous difference across the hind-limb; this effect of insulin was decreased by lactation, suggesting that lactation induces insulin resistance in skeletal muscle. 3. Lactation increased but insulin infusion decreased the plasma concentrations of acetate, beta-hydroxybutyrate and non-esterified fatty acids. 4. Insulin infusion decreased the arterio-venous differences of acetate and hydroxybutyrate across the hind-limb; this effect of insulin is probably indirect, resulting from the decrease in plasma concentrations of these metabolites. 5. Infusion of insulin had no effect on the glucose arterio-venous difference across the mammary gland, but did decrease the oxygen arterio-venous difference. 6. The results suggest that lactation results in insulin resistance in skeletal muscle, at least with respect to glucose utilization; this should facilitate the preferential utilization of glucose by the mammary gland. PMID- 2241912 TI - Contribution of glycerol and alanine to basal hepatic glucose production in the genetically obese (fa/fa) rat. AB - Increased hepatic glucose production has been reported to occur in the insulin resistant genetically obese fa/fa rats. The possible existence of an increased basal gluconeogenesis in obese rats was investigated, upon comparing the metabolic fate of glycerol and alanine in liver of fed anaesthetized lean and genetically obese (fa/fa) rats. Glycerol turnover rate in obese animals was 3 times that of the lean. This increase in glycerol turnover rate was associated with an increase in blood glycerol levels in obese animals. The contribution of glycerol to glucose production was significantly increased in obese animals. In contrast, the contribution of alanine to the hepatic glucose production was similar to lean and obese animals. A higher incorporation of glucose, glycerol and alanine into hepatic lipids was observed in obese animals than in controls. It is concluded that in fed genetically obese (fa/fa) rats the high blood glycerol concentrations is a major driving force for the increased basal hepatic conversion of this substrate into glucose. PMID- 2241911 TI - The relationship of rat liver overt carnitine palmitoyltransferase to the mitochondrial malonyl-CoA binding entity and to the latent palmitoyltransferase. AB - 1. Confirming previous work [Murthy & Pande (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 378-382], malonyl-CoA-inhibitable carnitine palmitoyltransferase (CPT1) from rat liver was found to be localized in outer rather than in inner mitochondrial membranes. 2. Antisera were raised against a liver mitochondrial CPT of Mr 68,000, which was presumed to be the latent from of the enzyme (CPT2). These antisera cross-reacted with solubilized CPT extracted from liver inner mitochondrial membranes and with polypeptides of Mr 68,000 and 60,000 in immunoblots of both inner and outer mitochondrial membranes. The antisera also precipitated CPT activity from detergent-treated total membrane and outer membrane preparations. 3. The antisera did not precipitate [14C]malonyl-CoA binding material obtained either from total membranes or from outer membranes. 4. It was concluded that liver CPT1 and CPT2 have some epitopes in common and may have a similar subunit size. In addition, CPT1 and the entity that binds malonyl CoA must be separated polypeptides. PMID- 2241913 TI - Recycling of glucosylceramide and sphingosine for the biosynthesis of gangliosides and sphingomyelin in rat liver. AB - It was previously shown that sphingomyelin and gangliosides can be biosynthesized starting from sphingosine or sphingosine-containing fragments which originated in the course of GM1 ganglioside catabolism. In the present paper we investigated which fragments were specifically re-used for sphingomyelin and ganglioside biosynthesis in rat liver. At 30 h after intravenous injection of GM1 labelled at the level of the fatty acid ([stearoyl-14C]GM1) or of the sphingosine ([Sph-3H]) moiety, it was observed that radioactive sphingomyelin was formed almost exclusively after the sphingosine-labelled-GM1 administration. This permitted the recognition of sphingosine as the metabolite re-used for sphingomyelin biosynthesis. Conversely, gangliosides more complex than GM1 were similarly radiolabelled after the two treatments, thus ruling out sphingosine re utilization for ganglioside biosynthesis. For the identification of the lipid fragment re-used for ganglioside biosynthesis, we administered to rats neutral glycosphingolipids (galactosylceramide, glucosylceramide and lactosylceramide) each radiolabelled in the sphingosine moiety or in the terminal sugar residue. Thereafter we compared the formation of radiolabelled gangliosides in the liver with respect to the species administered and the label location. After galactosylceramide was injected, no radiolabelled gangliosides were formed. After the administration of differently labelled glucosylceramide, radiolabelled gangliosides were formed, regardless of the position of the label. After lactosylceramide administration, the ganglioside fraction became more radioactive when the long-chain-base-labelled precursors were used. These results suggest that glucosylceramide, derived from glycosphingolipid and ganglioside catabolism, is recycled for ganglioside biosynthesis. PMID- 2241914 TI - Computer program for the expression of the kinetic equations of enzyme reactions as functions of the rate constants and the initial concentrations. AB - A versatile computer program with an easy input method has been developed for the construction of the terms in kinetic equations of enzyme reactions. It allows the expression of the time-dependence of the concentrations of all of the species involved as functions of the kinetic parameters. The mathematical theory used in this paper, the program and examples of its use have been deposited as Supplementary Publication SUP 50159 (41 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1990) 265, 5. PMID- 2241916 TI - Sensitivity of system A and ASC transport activities to thiol-group-modifying reagents in rat liver plasma-membrane vesicles. Evidence for a direct binding of N-ethylmaleimide and iodoacetamide on A and ASC carriers. AB - 1. In the present study we have examined the sensitivity of A and ASC amino-acid carrier activities in rat liver plasma-membrane vesicles to the thiol-group modifying reagents N-ethylmaleimide (NEM) and iodoacetamide (IA). To this end, the different Na(+)-dependent entities involved in alanine transport were assessed. 2. NEM inactivated Na(+)-dependent alanine transport as a result of the inhibition of both system A and ASC transport activities. The functional sensitivity of system A to NEM was greater than that of system ASC. 3. The presence of L-alanine (10 mM) during the exposure of vesicles to NEM afforded partial protection to system A, but not to the ASC, carrier. This effect was specific, since the presence of L-phenylalanine (10 mM) did not cause any protection. 4. Na+ did not protect A or ASC carriers against NEM inactivation; however, the presence of Na+ (100 mM-NaCl) and L-alanine (10 mM) during the exposure of the vesicles to NEM protected against inactivation of system A and ASC transport activities. The extent of protection was greater in the case of the system ASC transport activity than in the case of the A carrier. 5. IA also diminished Na(+)-dependent alanine transport by inhibition of A and ASC transport activities. Sodium and L-alanine afforded protection to both A and ASC transport activities from the inhibitory action of IA. The extent of protection induced by substrates was similar for both carriers. 6. It is concluded that there is one, or several, free thiol groups in A and ASC carriers, the integrity of which is essential for transport activity. Sensitivity to thiol-group-specific reagents and the pattern of protection with substrates against inactivation is different in A and ASC carriers. That suggests the existence of topological dissimilarities regarding the thiol-group containing site(s) in A and ASC amino acid carriers. PMID- 2241917 TI - N1N8-bis(gamma-glutamyl)spermidine cross-linking in epidermal-cell envelopes. Comparison of cross-link levels in normal and psoriatic cell envelopes. AB - N1N8-Bis(gamma-glutamyl)spermidine was found in exhaustive proteolytic digests of isolated cell envelopes from human epidermis at levels comparable with those of epsilon-(gamma-glutamyl)lysine. Significantly higher than normal amounts of these compounds, particularly the bis(gamma-glutamyl)polyamine, were observed in envelopes from afflicted areas (scales) of psoriatic patients. These findings support the notions that N1N8-bis(gamma-glutamyl)spermidine, like epsilon-(gamma glutamyl)lysine, functions in cell envelopes as an enzyme-generated protein cross link and stabilizing force and that individuals with the chronic, recurrent skin disease, psoriasis, exhibit in involved epidermis abnormal cell-envelope-protein cross-linking. PMID- 2241918 TI - Human hepatic N-acetylglutamate content and N-acetylglutamate synthase activity. Determination by stable isotope dilution. AB - N-Acetyl-L-glutamate (N-acetylglutamate) content and N-acetylglutamate synthase activity ranges were established in human liver tissue homogenates by stable isotope dilution. The methods employ N-[methyl-2H3]acetyl[15N]glutamate as internal standard, extraction of N-acetylglutamate by anion-exchange technique and its determination by g.l.c.-mass spectrometry by using selected ion monitoring. Hepatic N-acetylglutamate content in 16 different human livers, normal in structure and function, ranged from 6.8 to 59.7 nmol/g wet wt. (25.0 +/ 13.4 mean +/- S.D.) or from 64.6 to 497.6 nmol/g of protein (223.2 +/- 104.2 mean +/- S.D.). In vitro, N-acetylglutamate synthase activity in liver tissue homogenate ranged from 44.5 to 374.5 (132.0 +/- 90.6 mean +/- S.D.) nmol/min per g wet wt. or from 491.7 to 3416.9 (1159.6 +/- 751.1 mean +/- S.D.) nmol/min per g of protein. No correlation was found between hepatic N-acetylglutamate concentrations and the respective maximal enzymic activities in vitro of N acetylglutamate synthase. The marked variability in this system among individual livers may reflect its regulatory role in ureagenesis. PMID- 2241915 TI - The structure and function of human IgA. PMID- 2241919 TI - Circulating C-terminal propeptide of type I procollagen is cleared mainly via the mannose receptor in liver endothelial cells. AB - The fate of the circulating C-terminal propeptide of type I procollagen (PICP) was studied. Trace amounts of 125I-PICP administered intravenously to rats disappeared from the blood with an initial t1/2 of 6.1 min. After 45 min the radioactivity was distributed as follows: liver, 36%; blood, 23%; kidneys, 18%; urine, 20%; spleen, 1%; lungs, 2%; heart, 0.4%. To prevent escape of label from the site of uptake, PICP was labelled with 125I-tyramine cellobiose (125I-TC), which is trapped intralysosomally. With this ligand a serum t1/2 of 8.7 min was recorded, and 70% and 20% was traced in the liver and kidneys respectively. The uptake per liver endothelial cell (LEC) was 1000 times that per parenchymal cell and twice that per Kupffer cell. At 1 h and 6 h after addition of 125I-PICP to cultured LEC, 15% and 45% respectively, had been endocytosed. Only ligands for the mannose receptor could compete with PICP for endocytosis. To study whether the same specificity was operative in vivo, 125I-PICP was injected along with an excess of ovalbumin, which is known to be endocytosed by the mannose receptor of LEC. The serum t1/2 was prolonged from 6 to 16 min, signifying that terminal mannose residues are an important signal for clearance of PICP. In conclusion, these studies show that LEC constitute the main site of uptake of circulating PICP. The uptake is mediated by endocytic receptors which recognize terminal mannose residues. PMID- 2241920 TI - A pH-dependent activation-inactivation equilibrium in glutamate dehydrogenase of Clostridium symbiosum. AB - 1. On transferring Clostridium symbiosum glutamate dehydrogenase from pH 7 to assay mixtures at pH 8.8, reaction time courses showed a marked deceleration that was not attributable to the approach to equilibrium of the catalysed reaction. The rate became approximately constant after declining to 4-5% of the initial value. Enzyme, stored at pH 8.8 and assayed in the same mixture, gave an accelerating time course with the same final linear rate. The enzyme appears to be reversibly converted from a high-activity form at low pH to a low-activity form at high pH. 2. Re-activation at 31 degrees C upon dilution from pH 8.8 to pH 7 was followed by periodic assay of the diluted enzyme solution. At low ionic strength (5 mM-Tris/HCl), no re-activation occurred, but various salts promoted re-activation to a limiting rate, with full re-activation in 40 min. 3. Re activation was very temperature-dependent and extremely slow at 4 degrees C, suggesting a large activation energy. 4. 2-Oxoglutarate, glutarate or succinate (10 mM) accelerated re-activation; L-glutamate and L-aspartate were much less effective. 5. The monocarboxylic amino acids alanine and norvaline appear to stabilize the inactive enzyme: 60 mM-alanine does not promote re-activation, and, as substrates at pH 8.8 for enzyme stored at pH 7, alanine and norvaline give progress curves showing rapid complete inactivation. 6. Mono- and di-nucleotides (AMP, ADP, ATP, NAD+, NADH, NADP+, CoA, acetyl-CoA) at low concentrations (10(-4) 10(-3) M) enhance re-activation at pH 7 and also retard inactivation at pH 8.8. 7. The re-activation rate is independent of enzyme concentration: ultracentrifuge experiments show no changes in molecular mass with or without substrates. 8. The activation-inactivation appears to be due to a slow pH-dependent conformational change that is sensitively responsive to the reactants and their analogues. PMID- 2241921 TI - Acinar zonation of cytosolic but not organelle-bound activities of phosphoenolpyruvate carboxykinase and aspartate aminotransferase in guinea-pig liver. AB - In human liver, unlike in rat liver, there is no apparent acinar heterogeneity of total cellular activity of phosphoenolpyruvate carboxykinase [Wimmer, Luttringer & Columbi (1990) Histochemistry 93, 409-415]. Since the intracellular compartmentation of phosphoenolpyruvate carbonxykinase differs in rat and human liver, we examined the acinar heterogeneity of cytosolic and organelle-bound activities of this enzyme in the guinea pig, which shows a more similar intracellular compartmentation of enzyme activity to human liver than does the rat. Cytosolic phosphoenolpyruvate carboxykinase activity was higher in periportal than in perivenous hepatocytes, whereas the organelle-bound activity was similar in the two cell populations. Aspartate aminotransferase and alanine aminotransferase activities showed a similar distribution to phosphoenolpyruvate carboxykinase, with a higher cytosolic activity in periportal than in perivenous hepatocytes but a similar organelle-bound activity in the two cell populations. Data on the acinar zonation of enzymes determined in whole cells or tissue should be interpreted cautiously if the enzyme activity is present in more than one subcellular compartment. PMID- 2241923 TI - Glucose utilization by skeletal muscles in vivo in experimental hyperthyroidism in the rat. AB - In the fed state, hyperthyroidism increased glucose utilization indices (GUIs) of skeletal muscles containing a lower proportion of oxidative fibres. Glycogen concentrations were unchanged, but active pyruvate dehydrogenase (PDHa) activities were decreased. Hyperthyroidism attenuated the effects of 48 h of starvation to decrease muscle GUI. Glycogen concentrations and PDHa activities after 48 h of starvation were low and similar in euthyroid and hyperthyroid rats. The increase in glucose uptake and phosphorylation relative to oxidation and storage in skeletal muscle induced by hyperthyroidism may contribute to increased glucose re-cycling in the fed hyperthyroid state and to glucose turnover in the starved hyperthyroid state. PMID- 2241922 TI - A role for polyamines in glucose-stimulated insulin-gene expression. AB - The aim of the present study was to evaluate the possible role for polyamines in the glucose regulation of the metabolism of insulin mRNA of pancreatic islet cells. For this purpose islets were prepared from adult mice and cultured for 2 days in culture medium RPMI 1640 containing 3.3 mM- or 16.7 mM-glucose with or without the addition of the inhibitors of polyamine biosynthesis difluoromethylornithine (DFMO) and ethylglyoxal bis(guanylhydrazone) (EGBG). Culture at the high glucose concentration increased the islet contents of both insulin mRNA and polyamines. The synthesis of total RNA, total islet polyamines and polyamines associated with islet nuclei was also increased. When the combination of DFMO and EGBG was added in the presence of 16.7 mM-glucose, low contents of insulin mRNA, spermine and spermidine were observed. Total islet polyamine synthesis was also depressed by DFMO + EGBG, unlike islet biosynthesis of polyamines associated with nuclei, which was not equally decreased by the polyamine-synthesis inhibitors. Total RNA synthesis and turnover was not affected by DFMO + EGBG. Finally, actinomycin D attenuated the glucose-induced enhancement of insulin mRNA, and cycloheximide counteracted the insulin-mRNA attenuation induced by inhibition of polyamine synthesis. It is concluded that the glucose induced increase in insulin mRNA is paralleled by increased contents and rates of polyamine biosynthesis and that an attenuation of the increase in polyamines prevents the increase in insulin mRNA. In addition, the results are compatible with the view that polyamines exert their effects on insulin mRNA mainly by increasing the stability of this messenger. PMID- 2241924 TI - An analysis of the reaction kinetics of the hexahaem nitrite reductase of the anaerobic rumen bacterium Wolinella succinogenes. AB - The reduction kinetics of both the resting and redox-cycled forms of the nitrite reductase from the anaerobic rumen bacterium Wolinella succinogenes were studied by stopped-flow reaction techniques. Single-turnover reduction of the enzyme by dithionite occurs in two kinetic phases for both forms of the enzyme. When the resting form of the enzyme is subjected to a single-turnover reduction by dithionite, the slower of the two kinetic phases exhibits a hyperbolic dependence of the rate constant on the square root of the reductant concentration, the limiting value of which (approximately 4 s-1) is assigned to a slow internal electron-transfer process. In contrast, when the redox-cycled form of the enzyme is reduced by dithionite in a single-turnover experiment, both kinetic phases exhibit linear dependences of the rate on the square root of dithionite concentration, with associated rate constants of 150 M-1/2.s-1 and 6 M-1/2.s-1. Computer simulations of both the reduction processes shows that no unique set of rate constants can account for the kinetics of both forms, although the kinetics of the redox-cycled species is consistent with a much enhanced rate of internal electron transfer. Under turnover conditions the time course for reduction of the enzyme, in the presence of millimolar levels of nitrite and 100 mM-dithionite, is extremely complex. A working model for the mechanism of the turnover activity of the enzyme is proposed which very closely describes the reaction kinetics over a wide range of substrate concentrations, as shown by computer simulation. The similarity in the action of the nitrite reductase enzyme and mammalian cytochrome c oxidase is commented upon. PMID- 2241925 TI - Two types of receptors for iron on mitochondria. AB - ATP, the major ligand for Fe in the reticulocyte's low-Mr chelatable pool, transfers Fe to a mitochondrial receptor from which the Fe is incorporated into haem. However, the utilization of Fe bound to this receptor for haem synthesis is slow in comparison with that bound to a second receptor that does not accept Fe from ATP, but does accept it from AMP. The major pathway by which Fe is delivered for haem synthesis may be through hydrolysis of cytosolic ATP-Fe to AMP-Fe. PMID- 2241926 TI - Calreticulin is a candidate for a calsequestrin-like function in Ca2(+)-storage compartments (calciosomes) of liver and brain. AB - In a search for the non-muscle equivalent of calsequestrin (the low-affinity high capacity Ca2(+)-binding protein responsible for Ca2+ storage within the terminal cisternae of the sarcoplasmic reticulum), acidic proteins were extracted from rat liver and brain microsomal preparations and purified by column chromatography. No calsequestrin was observed in these extracts, but the N-terminal amino acid sequence of the major Ca2(+)-binding protein of the liver microsomal fraction was determined and found to correspond to that of calreticulin. This protein was found to bind approx. 50 mol of Ca2+/mol of protein, with low affinity (average Kd approx. 1.0 mM). A monoclonal antibody, C6, raised against skeletal-muscle calsequestrin cross-reacted with calreticulin in SDS/PAGE immunoblots, but polyclonal antibodies reacted with native calreticulin only weakly, or not at all, after SDS denaturation. Immuno-gold decoration of liver ultrathin cryosections with affinity-purified antibodies against liver calreticulin revealed luminal labelling of vacuolar profiles indistinguishable from calciosomes, the subcellular structures previously identified by the use of anti calsequestrin antibodies. We conclude that calreticulin is the Ca2(+)-binding protein segregated within the calciosome lumen, previously described as being calsequestrin-like. Because of its properties and intraluminal location, calreticulin might play a critical role in Ca2+ storage and release in non-muscle cells, similar to that played by calsequestrin in the muscle sarcoplasmic reticulum. PMID- 2241928 TI - Quantitative control analysis of branched-chain 2-oxo acid dehydrogenase complex activity by feedback inhibition. AB - The potential for branched-chain 2-oxo acid dehydrogenase complex (BCOADC) activity to be controlled by feedback inhibition was investigated by calculating the Elasticity Coefficients for several feedback inhibitors. We suggest that feedback inhibition is a quantitatively important regulatory mechanism by which branched-chain 2-oxo acid dehydrogenase activity is regulated. The potential for control of enzyme activity is greater for NADH than for the acyl-CoA products, and suggests that factors that alter the redox potential may physiologically regulate BCOADC activity through a feedback inhibitory mechanism in vivo. Local pH may also be an important regulatory control factor. PMID- 2241927 TI - Glutathione transferase isoenzymes from human prostate. AB - By using affinity-chromatography and isoelectric-focusing techniques, several forms of glutathione transferase (GSTs) were resolved from human prostate cytosol. All the three major classes of GST, i.e. Alpha, Mu and Pi, are present in human prostate. However, large inter-individual variation in the qualitative and quantitative expression of different isoenzymes resulted in the samples investigated. The most abundant group of prostate isoenzymes showed acid (pI 4.3 4.7) behaviour and were classified as Pi class GSTs on the basis of their immunological and structural properties. Immunohistochemical staining of Pi class GSTs was prevalently distributed in the epithelial cells surrounding the alveolar lumen. Class Mu GSTs are also expressed, although in small amounts and in a limited number of samples, by human prostate. The major cationic isoenzyme purified from prostate, GST-9.6; (pI 9.6; apparent subunit molecular mass of 28 kDa), appears to be different from the cationic GST alpha-epsilon forms isolated from human liver and kidney as evidenced by its structural, kinetical and immunological properties. This enzyme, which accounts for about 20-30% (on protein basis) of total amount of GSTs, is expressed by only 40% of samples. GST 9.6 has the ability to cross-react in immunoblotting analysis with antisera raised against rat liver GST 2-2, rather than with antisera raised against members of human Alpha, Mu and Pi class GSTs. Although prostate GST-9.6 shows close relationship with the human skin GST pI 9.9, it does not correspond to any other known human GST. PMID- 2241929 TI - Purification and characterization of 4-methylmuconolactone methylisomerase, a novel enzyme of the modified 3-oxoadipate pathway in the gram-negative bacterium Alcaligenes eutrophus JMP 134. AB - 4-Carboxymethyl-4-methylbut-2-en-4-olide (4-methyl-2-enelactone) isomerase, transforming 4-methyl-2-enelactone to 3-methyl-2-enelactone, was purified from a derivative strain of Pseudomonas sp. B13, named B13 FR1, carrying the plasmid pFRC2OP. This plasmid contained the isomerase gene cloned from Alcaligenes eutrophus JMP 134, which uses 4-methyl-2-enelactone as a carbon source. The enzyme consists of a single peptide chain of Mr 40,000 as judged by SDS/PAGE. In addition to 4-methyl-2-enelactone, the putative reaction intermediate, 1-methyl 3,7-dioxo-2,6-dioxy-bicyclo[3.3.0]octane (1-methylbislactone), was a substrate for the enzyme, but kinetic data presented did not favour its role as a reaction intermediate. Isomeric methyl-substituted 4-carboxymethylbut-2-en-4-olides were neither substrates nor inhibitors. Possible reaction mechanisms are discussed. PMID- 2241930 TI - Denaturation studies on natural and recombinant bovine prochymosin (prorennin). AB - 1. Prochymosin in solution in the presence of 8 M-urea is fully unfolded, as indicated by its fluorescence spectrum, fluorescence quenching behaviour and far u.v.c.d. spectrum. 2. Equilibrium studies on the unfolding of prochymosin and pepsinogen by urea were carried out at pH 7.5 and pH 9.0. The results indicate that the stabilization energies of the two proteins are identical at pH 7.5, but that at pH 9.0 pepsinogen is significantly less stable than prochymosin. 3. Kinetic studies on the unfolding of prochymosin and pepsinogen indicate that the processes can be described by a single first-order rate constant, and that at any given value of denaturant concentration and pH the rate of unfolding of prochymosin is significantly greater than that of pepsinogen. 4. Unfolding of prochymosin by concentrated urea is not fully reversible, unlike that of pepsinogen. Kinetic analysis of the refolding of the proteins suggests the presence of a slow process following unfolding in urea; for pepsinogen this process leads to a slowly refolding form, whereas for prochymosin the slow process in urea leads to a form that cannot refold on dilution of the denaturant. 5. The results provide a rationale for an empirical process for recovery of recombinant prochymosin after solubilization of inclusion bodies in concentrated urea. 6. In all respects studied here, natural and recombinant bovine prochymosin were indistinguishable, indicating that the refolding protocol yields a recombinant product identical with natural prochymosin. PMID- 2241931 TI - Synergistic control of Ca2+ mobilization in permeabilized mouse L1210 lymphoma cells by inositol 2,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. AB - L1210 lymphoma cells were permeabilized with digitonin, and the ability of Ins(2,4,5)P3 and Ins(1,3,4,5)P4 to mobilize intracellular Ca2+ was studied. At high doses of Ins(2,4,5)P3 Ca2+ was rapidly released from intracellular stores, and prior or subsequent addition of Ins(1,3,4,5)P4 had no discernible effect. However, the Ca2(+)-mobilizing action of low (threshold or just above) concentrations of Ins(2,4,5)P3 was markedly enhanced by Ins(1,3,4,5)P4, which alone caused no mobilization of Ca2+; this phenomenon was shown not to be due to protection of Ins(2,4,5)P3 by the Ins(1,3,4,5)P4 against hydrolysis. The ability of the pre-addition of Ins(1,3,4,5)P4 to enhance subsequent Ins(2,4,5)P3-induced Ca2+ mobilization was always seen whether or not the free Ca2+ concentration was low (pCa = 7) or high (pCa = 6). However, at low Ca2+, Ins(1,3,4,5)P4 could cause a further mobilization if added after the Ins(2,4,5)P3, whereas at higher Ca2+ values Ins(1,3,4,5)P4 was only able to affect Ca2+ if added before Ins(2,4,5)P3. These effects of Ins(1,3,4,5)P4 were not, at the same concentration, mimicked by a random mixture of InsP4 isomers obtained by partial acid hydrolysis of phytic acid, by Ins(1,3,4)P3 or by Ins(1,3,4,5,6)P5, and they were shown not to be due to enzymic generation of Ins(1,4,5)P3 from Ins(1,3,4,5)P4 by (a) the absence of any detectable production of Ins(1,4,5)P3 if radiolabelled Ins(1,3,4,5)P4 was used, or (b) the observation that Ins(1,3,4,5,6)P5 could mimic Ins(1,3,4,5)P4 provided that higher doses were used; this inositol phosphate, when added radiolabelled, yielded only trace quantities of D/L-Ins(1,4,5,6)P4, which itself does not mobilize Ca2+. We interpret these results overall to mean that in these cells there is a small proportion of the Ins(2,4,5)P3-mobilizable Ca2+ pools which can only be mobilized in the presence of Ins(1,3,4,5)P4 [or at the least, Ins(1,3,4,5)P4 can help Ins(2,4,5)P3 to gain access to them]. The significance of this conclusion is discussed in the light of current concepts of the second messenger function of Ins(1,3,4,5)P4. PMID- 2241932 TI - Slow tight-binding inhibition of prolyl endopeptidase by benzyloxycarbonyl-prolyl prolinal. AB - Prolyl endopeptidase is a serine proteinase that specifically cleaves peptides on the carboxy side of proline residues. Wilk & Orlowski [(1983) J. Neurochem. 41, 69-75] have shown that benzyloxycarbonyl-prolyl-prolinal (Z-prolyl-prolinal) is a potent inhibitor of prolyl endopeptidase. We show that Z-prolyl-prolinal is a slow-binding inhibitor of mouse brain prolyl endopeptidase with Ki 0.35 +/- 0.05 nM. Kinetic analysis indicates that the mechanism is a simple, but slow, reversible equilibrium between free and bound enzyme (E + I in equilibrium EI) with rate constants for association (kon) and dissociation (koff) of 1.6 X 10(5) M-1.s-1 and approx. 4 X 10(-5) s-1 respectively. Slow-binding inhibition is dependent on the presence of the aldehyde group since the alcohol (Z-prolyl prolinol) is a rapid and 50,000-fold poorer inhibitor (Ki 19 microM). Prolyl endopeptidase from human brain is also inhibited by Z-prolyl-prolinal with kinetics similar to those of the mouse brain enzyme. PMID- 2241933 TI - Telomeres, telomerase and senescence. AB - Eukaryotic chromosomes end with tandem repeats of simple sequences. These GC rich repeats allow telomere replication and stabilize chromosome ends. Telomere replication involves an equilibrium of sequence loss and addition at the ends of chromosomes. Repeats are added de novo by telomerase, an unusual DNA polymerase. Telomerase is an RNP in which an essential RNA component provides the template for the added telomere repeats. Telomere length maintenance plays an essential role in cell viability. PMID- 2241934 TI - From cell membrane to nucleotides: the phosphate regulon in Escherichia coli. AB - Most of the essential cellular components, like nucleic acids, lipids and sugars, are phosphorylated. The phosphate equilibrium in Escherichia coli is regulated by the phosphate (Pi) input from the surrounding medium. Some 90 proteins are synthesized at an increased rate during Pi starvation and the global control of the cellular metabolism requires cross-talk with other regulatory mechanisms. Since the Pi concentration is normally low in E. coli's natural habitat, these cells have devised a mechanism for synthesis of about 15 proteins to accomplish two specific functions: transport of Pi and its intracellular regulation. The synthesis of these proteins is controlled by two genes (the phoB-phoR operon), involving both negative and positive functions. PhoR protein is a histidine protein kinase, induced in Pi starvation and is a transmembrane protein. It phosphorylates the regulator protein PhoB which is also Pi starvation-induced. The PhoB phosphorylated form binds specifically to a DNA sequence of 18 nucleotides (the pho Box), which is part of the promoters of the Pho genes. The genes controlled by phoB constitute the Pho regulon. The repression of phoA (the gene encoding alkaline phosphatase) by high Pi concentrations in the medium requires the presence of an intact Pst operon (pstS, pstC, pstA, pstB and phoU) and phoR. The products of pstA and pstC are membrane bound, whereas the product of pstS is periplasmic and PstB and PhoU proteins are cytoplasmic. The function of the PhoU protein may be regulated by cofactor nucleotides and may be involved in signaling the activation of the regulon via PhoR. PMID- 2241935 TI - At the crossroads of developmental genetics: the cloning of the classical mouse T locus. AB - The discovery, more than 60 years ago, of a mutant mouse with a short tail led to the birth of the new field of developmental genetics. Over the years since, numerous investigators have probed the biology of the original short-tail mutation at the T locus, as well the naturally-occurring t haplotypes that were uncovered as a result of their interaction with this mutation. Although the T locus ranks among the best characterized developmental loci in the mouse, it was not among the first to be cloned. This situation has now been rectified with two recent reports from Herrmann, Lehrach and their colleagues. While the T locus is expressed uniquely in the embryonic tissues predicted from the mutant phenotype, the gene itself, as well as the predicted amino acid sequence of the T product, show no strong homology to any known sequence. For the moment, at least, the mystery behind the function of the T locus still awaits definitive resolution. PMID- 2241936 TI - Position effects, methylation and inherited epigenetic states. PMID- 2241937 TI - Traction and the formation of mesenchymal condensations in vivo. AB - Although the segregation of mesenchyme into distinct aggregates is the first step in the development of a range of tissues that includes bones, somites, feathers and nephrons, we still know very little about the mechanisms by which this happens. There are two obvious types of explanation: first, that there are global pre-patterns within the mesenchyme whose molecular expression leads to tissue fragmentation and, second, that the condensations arise spontaneously through the local morphogenetic abilities of the cells. The only known mechanism for the latter possibility is cell traction and this paper suggests that current studies are compatible with traction playing a primary role in the formation of nephrogenic condensations in the developing kidney and the separation of somites, but not for the generation of feather rudiments where there is evidence of a prepattern of adhesivity. PMID- 2241938 TI - The difference in murine CDC2 kinase activity between cytoplasmic and nuclear fractions during the cell cycle. AB - The mouse analog of yeast CDC2+ kinase was detected in the cytoplasmic and nuclear fractions of cultured mouse FM3A cells. Its activity in the nuclear fraction increased in the G2/M phase became seven times higher than that in the G1/S phase, while the activity in the cytoplasmic fraction remained was almost constant from the G1/S to G1 phases. The activity in the cytoplasmic fraction was similar to that in the nuclear fraction in the G2/M phase. The amount of the enzyme remained almost constant during the cell cycle in both the nuclear and cytoplasmic fractions. These findings suggest that the cytoplasmic enzyme might play an independent role in the cell cycle. PMID- 2241939 TI - Antioxidant activity of 6-phosphatidyl-L-ascorbic acid. AB - The antioxidant activity of 6-phosphatidyl-L-ascorbic acid was investigated in a homogeneous solution and a liposomal suspension. In an apolar solvent, one molecule of 6-phosphatidyl-L-ascorbic acid could trap one peroxyl radical. When 6 phosphatidyl-L-ascorbic acid was included in multilamellar liposomes of egg yolk phosphatidylcholine, it could retard more effectively the aqueous peroxyl-induced peroxidation of phosphatidylcholine than L-ascorbic acid. PMID- 2241941 TI - Occurrence of transketolase abnormalities in extracts of foreskin fibroblasts from patients with Alzheimer's disease. AB - Foreskin fibroblast cell lines from healthy subjects and patients with Alzheimer's disease or other neurological disorders have been analyzed for transketolase, by means of isoelectrofocusing and specific immunostaining. The enzyme profile in 70% of Alzheimer cell cultures exhibits alterations which are not encountered in controls and in other neurological diseases examined. Enzyme abnormalities most frequently observed were the appearance of new transketolase forms having unusually high alkaline pI. Experiments carried out with intact cells and with cell extracts treated with and without phenylmethyl-sulphonyl fluoride, suggest that the peculiar transketolase abnormalities observed in Alzheimer fibroblasts are due to enhanced proteolysis occurring in these cells rather than to intrinsic enzyme lability. PMID- 2241940 TI - Inhibition of biological actions of big endothelin-1 by phosphoramidon. AB - Endothelin (ET)-1 and big ET-1 both caused contraction of isolated porcine coronary arteries, but the potency of big ET-1 was 1/100-1/200 that of ET-1. These responses were independent of the vascular endothelium. Phosphoramidon blocked the vasoconstriction caused by 30 nM big ET-1, but was ineffective on the action of 0.3 nM ET-1. Also in vivo, phosphoramidon had no effect on the ET-1 induced pressor actions, but blocked the pressor and airway-contractile responses to big ET-1 in rats and/or guinea pigs. Thus, it is likely that the vascular responses to exogenous big ET-1 are at least in part due to its conversion to ET 1 by a phosphoramidon-sensitive ET converting enzyme(s) in the vascular smooth muscle in vitro and in vivo. PMID- 2241942 TI - Induction of an altered DNA conformation by an inversion rearrangement in the 5' flanking DNA of a U1 RNA gene. AB - The anomalous electrophoretic behavior of a 686 base pair restriction fragment containing an in vitro-generated inversion mutation within the enhancer region of a chicken U1 RNA gene was investigated. This DNA fragment migrated with an abnormally slow mobility in polyacrylamide gels but migrated normally in agarose gels relative to the wild type fragment of identical size and base composition. In polyacrylamide gels, the degree of retardation was enhanced at low temperature, a phenomenon associated with bent DNA. A putative site of bending was localized at or near one end of the inverted region. These data suggest that the altered DNA conformation results from the juxtaposition of two normally remote DNA sequences. PMID- 2241943 TI - Protein kinase C activation selectively increases mRNA levels for one of the regulatory subunits (RI alpha) of cAMP-dependent protein kinases in HT-29 cells. AB - We have examined the effect of the protein kinase C activator, TPA, on mRNA levels for subunits of cAMP-dependent protein kinases in the human colonic cancer cell line HT-29, subline m2. Messenger RNA for the regulatory subunit, RI alpha, of cAMP-dependent protein kinases was shown to be present and regulated by TPA. Other mRNAs for subunits of cAMP-dependent protein kinases (RI beta, RII alpha, RII beta, C alpha, C beta) were also present in these cells, but revealed no or only minor changes upon TPA stimulation. When HT-29 cells were cultured in the presence of 10 nM TPA for various time periods, a biphasic response was observed in RI alpha mRNA levels with a maximal increase (approximately 4 fold) after 24 hours. TPA stimulated RI alpha mRNA increased in a concentration-dependent manner and maximal response (4-8 fold) was seen at 3-10 nM. The TPA-induced increase in RI alpha mRNA was not obtained when cells were incubated with TPA together with the protein kinase C inhibitors, staurosporine or H7. The cAMP-analog 8-CPTcAMP alone induced RI alpha mRNA levels 50% more than TPA. Combined treatment with TPA (10 nM) and 8-CPTcAMP (0.1 mM) gave an increase in RI alpha mRNA similar to TPA. These results demonstrate an interaction between the protein kinase C pathway and mRNA levels for the RI alpha subunit of cAMP-dependent protein kinases in HT-29 cells. PMID- 2241944 TI - The binding of ATP and AMP to Escherichia coli adenylate kinase investigated by 1H and 15N NMR spectroscopy. AB - [N6 15N]ATP and [N6 15N]AMP, complexed with E.coli adenylate kinase (AKe), were observed with 15N isotope-filtered NMR pulse sequences and 1H[15N] heterocorrelated experiments to determine differences between binding sites based on chemical shifts and competition by substrate analogs. The chemical shifts of the N6 amino proton and nitrogen signals changed significantly after mixing with adenylate kinase. Differences in chemical shifts between the bound ATP and AMP signals are slight. The response of these shifts to further addition of other substrates or Mg2+ supports the view that the unchelated nucleotides can bind to both the sites, whereas the metal complexed species are restricted to the MgATP/MgADP binding site. PMID- 2241945 TI - Characterization and behaviour of 15-lipoxygenase during peanut cotyledonary senescence. AB - Lipoxygenase (EC 1.13.11.12) (LOX), a ubiquitous plant enzyme which catalyzes the hydroperoxidation of unsaturated fatty acids (PUFA), plays an important role during the course of leaf and cotyledonary senescence. In the present study, senescence related changes in chlorophyll and protein content and lipoxygenase activity have been examined in peanut cotyledons. The chlorophyll content of the cotyledons increased from the 2nd to 8th day followed by a steady decline. In contrast, protein content of peanut cotyledons decreased continuously during senescence. Lipoxygenase activity, on the other hand, increased in early stages of germination followed by a decrease in the later course of senescing peanut cotyledons. Analysis of the product profile, the lipoxygenase with arachidonic acid as the substrate on HPLC, has shown a single peak comigrating with standard 15-Hydroperoxyeicosatetraenoic acid. The results on peanut cotyledonary 15 lipoxygenase activity in relation to abscisic acid and kinetin are discussed. PMID- 2241946 TI - Inhibition of TGF alpha-induced second messengers by anti-EGF receptor antibody 425. AB - Monoclonal antibody 425 binds to a protein epitope of the human EGF receptor and blocks EGF dependent functions such as EGF receptor phosphorylation and mitogenesis (1). We now show that MAb 425 blocks TGF alpha-induced second messenger signals, namely inositol 1,4,5 triphosphate and Ca2+ in two carcinoma cell lines, A 431 and SW-948. In this study we have further characterized the specificity of this antibody for inhibiting TGF alpha induced mitogenesis in MRC 5, a EGF-receptor expressing fibroblast cell line. PMID- 2241947 TI - Removal of twelve C-terminal amino acids from firefly luciferase abolishes activity. AB - cDNA coding for the luciferase in the firefly Photinus pyralis was cloned using pcDV1 primer and Honjo linker containing SP6 RNA polymerase promoter. This enabled conditions to be established to produce mRNA, capped with m7 GpppG, in vitro and then translated to form light emitting protein. Full length recombinant luciferase produced by in vitro translation, was fully active, had the same isoelectric focusing point as the native enzyme and produced a similar, yellow emission. Removal of the coding sequence for the last 12 amino acids at the C terminus, containing the peroxisome signal peptide, by polymerase chain reaction resulted in greater than or equal to 99% loss in activity of the protein formed from mRNA in vitro. This has important implications for using this luciferase as an indicator or reporter gene in eukaryotic cells, and for identifying the active centre of the enzyme. PMID- 2241948 TI - Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis. AB - Deleted mitochondrial DNA (mtDNA) was accumulated in the parkinsonian striatum, but the same deleted mtDNA was also detectable in the control striatum when cycles of polymerase chain reaction were increased. To discriminate between these pathological and physiological conditions, we quantitatively analyzed the proportion of deleted mtDNA to normal mtDNA by measuring the incorporation of alpha-[32P]deoxycytosine triphosphate into mtDNA fragments by using a laser image analyzer. To estimate the molar ratio of the deleted mtDNA to normal mtDNA, the radioactivity was normalized by each fragment size. By plotting logarithms of normalized radioactivities against PCR amplification cycles, straight lines were obtained with different slopes. By extrapolation of the line to the zero amplification, the proportion of mutant mtDNA to normal mtDNA in the original sample from the parkinsonian striatum was estimated to be ca. 5%, which was at least ten times higher than the proportion of ca. 0.3% in the control striatum. These results indicate that phenotype of the mutant mtDNA as Parkinson's disease is expressed when the proportion of deleted mtDNA to normal mtDNA exceeds a threshold of ten times higher value than in the normal subject. PMID- 2241950 TI - Autoantibodies specific for the 20-KDal ribosomal large subunit protein L12. AB - New antibodies reactive with a 20 KDal ribosomal protein of the large subunit were found in sera from two of eighty patients with systemic lupus erythematosus. This antigenic protein was identified as L12 by the mobility in two-dimensional gel electrophoresis. Both sera also contained anti-P activity against three acidic phosphoproteins (P proteins), but this activity was completely inhibited by preincubation with the isolated P proteins. Therefore, these anti-L12 can be useful for studying the function of L12 in protein synthesis. PMID- 2241949 TI - Identification of pristanoyl-CoA oxidase activity in human liver and its deficiency in the Zellweger syndrome. AB - The ability of human liver to oxidize pristanic acid was investigated. Liver from control subjects was found to contain pristanic acid oxidase activity, an H2O2 producing enzyme activity not previously demonstrated in mammals. In livers from patients with the cerebro-hepato-renal syndrome of Zellweger, a genetic disease characterized by the absence of morphologically distinguishable peroxisomes, pristanic acid oxidase activity was found to be deficient. These results indicate that pristanic acid is oxidized in peroxisomes rather than in mitochondria as believed until now. Furthermore, our findings provide an explanation for the elevated levels of pristanic acid in body fluids from patients lacking peroxisomes. PMID- 2241952 TI - Isolation of three allergenic fractions of the major allergen from Olea europea pollen and N-terminal amino acid sequence. AB - A method to isolate the major allergen from olive pollen (Ole e I) in high yield is described. The allergenic fraction has been separated into 3 subfractions by reverse-phase HPLC. All these fractions were reactive to allergic sera from olive sensitized patients, giving similar responses. No significant differences were observed between the amino acid compositions of these three proteins. The amino acid sequence of the first 27 amino acid residues from the N-terminal end is given. No homologies have been detected between Ole e I and other known allergens obtained from pollen. PMID- 2241951 TI - An ATP, calcium and voltage sensitive potassium channel in porcine coronary artery smooth muscle cells. AB - There is increasing interest in the roles played by potassium channels of smooth muscle in protecting against ischemic and anoxic insults. Hence, potassium selective channels were studied in freshly dispersed porcine coronary artery smooth muscle cells using the inside-out variant of the patch-clamp technique. The most abundant potassium channel had a conductance of 148 pS in a 5.4/140 mM K+ gradient, at 0 mV, and was regulated by cytoplasmic ATP (0.05-3.0 mM), cytoplasmic Ca2+ (0.1-10 microM) and voltage. ATP and AMP-PNP (0.5 mM) reduced the probability of channel opening (Po) by 87 and 92%, respectively. This inhibition was partially reversed by the addition of 0.5 mM ADP. ADP on its own (2 mM) reduced Po by 46%. It appears, therefore, that this channel shares properties with both the ATP-sensitive and the calcium-regulated potassium channels, raising the possibility that it plays a central role in the regulation of coronary blood flow. PMID- 2241953 TI - Isolation and characterization of a metalloproteinase secreted by rat glioma cells in serum-free culture. AB - The isolation of a metalloproteinase secreted by a rat glioma cell line (BT5C) in serum-free media is described. After affinity purification, the activity was present as a double band with Mr 86000 and 76000 both of which required CaCl2 for activity. The enzyme was able to degrade gelatin but not casein. It was unable to degrade native types I, III, IV and V collagens but their denatured counterparts were degraded. Using a radiolabel release assay the enzyme was inhibited by EDTA, 1:10 phenanthroline and TIMP confirming that it belongs to the family of metalloproteinases. Its activity was not affected by either serine or cysteine protease inhibitors. The proteinase was activated by APMA but was unaffected by trypsin treatment. PMID- 2241954 TI - Cultured astrocytoma cells inhibit platelet aggregation by releasing a nitric oxide-like factor. AB - Cultured astrocytoma cells were tested for their ability to generate a nitric oxide like factor using platelet aggregation as a bioassay. Incubation of astrocytoma cells with human washed platelets resulted in an inhibition of thrombin-induced platelet aggregation which was proportional to the number of astrocytoma cells added. The inhibition was potentiated by superoxide dismutase (SOD) and prevented by oxyhaemoglobin (oxyHb). The inhibitory activity of astrocytoma cells was also prevented by the NO biosynthesis inhibitor NG monomethyl-L-arginine (MeArg), an effect reversed by co-incubation with L arginine (L-Arg) but not D-arginine (D-Arg). These results demonstrate that astrocytoma cells release, independent of added agonist, a factor with the same pharmacological profile as NO, which is likely to be derived from L-arginine. PMID- 2241955 TI - Calcitonin gene-related peptide stimulates adenylate cyclase activity in trout gill cell membranes. AB - The physiological significance of calcitonin gene-related peptide (CGRP) was investigated by assessing the CGRP stimulated adenylate cyclase activity in various tissues of trout. The highest enzyme concentration was found in gill and stomach membranes. The maximal activity (190% of the basal value) was observed for a concentration of 53.3 nM CGRP I or II. In the presence of 58 nM sCT, the maximal enzyme activity represented 120% of the basal value. No additive effect was observed; this suggests that both CGRP and sCT activities are mediated through the same receptor. The present data are in favour of a role for this neuropeptide operating in branchial cell functions such as calcium transfer from the external to the internal milieu. PMID- 2241956 TI - Trehalose, the insect blood sugar, inhibits loading of diacylglycerol by lipophorin from the fat body in locusts. AB - Trehalose, the insect blood sugar, was found to inhibit diacylglycerol uptake by lipophorin from the fat body in vitro. Trehalose inhibited diacylglycerol uptake by about 40%-50% at various physiological concentrations. This suggests that trehalose may play a dual role in the hemolymph, i.e. serving as the insect's fuel and as a regulator in lipid transport. PMID- 2241957 TI - Neutral endopeptidase (EC 3.4.24.11) is highly expressed on osteoblastic cells and other marrow stromal cell types. AB - A series of cultured mouse marrow stromal cell lines of different phenotype characteristics were examined for their neutral endopeptidase (NEP) activity using the highly selective chromophoric substrate of enzyme, 3-carboxypropanoyl alanyl-alanyl-leucine 4-nitroanilide. All the cell lines tested contained appreciable amounts of NEP activity, but the cells expressing an osteoblastic phenotype, MBA-15, showed the high levels. Other non-stromal osteoblastic cell lines, MC-3T3-E1, ROS 17/2.8 cells derived from mouse long bone explants, were also rich in NEP. A four-fold stimulation of NEP activity was observed when certain MBA-15 clones were cultured in the presence of 1 alpha,25 dihydroxyvitamin D3. Since NEP is an effective cell-surface endopeptidase, it may play a role in the dynamics of bone formation, via interaction with biologically active polypeptides. PMID- 2241958 TI - A T-to-A substitution in the E1 alpha subunit gene of the branched-chain alpha ketoacid dehydrogenase complex in two cell lines derived from Menonite maple syrup urine disease patients. AB - We cloned and sequenced cDNAs of the E1 alpha and E1 beta subunits of the branched chain alpha-ketoacid dehydrogenase complex (BCKDH) in two cell lines derived from two different Menonite MSUD patients (GM 1655, GM 1099). A T-to-A substitution which generates an asparagine in place of a tyrosine at amino acid 394 of the mature E1 alpha subunit was present in both alleles in these two cell lines, whereas cDNAs of the E1 beta subunit in these cell lines were identical to that of normal human lymphoid cell line and that of the clone from a human placenta cDNA library. It is suggested that the Menonite MSUD is caused by the missense mutation of the E1 alpha subunit of the BCKDH complex. PMID- 2241959 TI - Insulin-like growth factor-I stimulates endothelin-3 secretion from rat anterior pituitary cells in primary culture. AB - Since we found relatively high concentrations of immunoreactive (ir-) ET-3 in the rat pituitary gland (190 pg/g tissue), we have investigated the possible ET-3 secretion from the primary culture of anterior pituitary cells and the effects of various growth factors on the ET-3 secretion. The ir-ET-3 was detected in the incubation medium within 2 h, and 24 h of culture attained the concentrations of 1.15 +/- 0.26 pg/well/6 x 10(5) cells. The ir-ET-3 secretion was stimulated by insulin, insulin like growth factor-II (IGF-II), and most effectively by insulin like growth factor-I (IGF-I) in a dose- and time-dependent manner, whereas the production of ir-ET-1 and ir-big ET-1 was slightly inhibited by IGF-I and IGF-II. In reverse-phase HPLC, the ir-ET-3 released into the culture media showed identical retention time with authentic ET-3. Although ir-ET-1 and ir-big ET-1 secretion was stimulated by transforming growth factor-beta (TGF-beta), ir-ET-3 secretion was inhibited. These results indicate that the anterior pituitary cells secrete ET-3 and the secretion is stimulated by IGF-I. PMID- 2241960 TI - Glutathione S-transferase in yeast: induction of mRNA, cDNA cloning and expression in Escherichia coli. AB - Glutathione S-transferase Y-2 mRNA synthesis was induced in yeast Issatchenkia orientalis approximately 37-fold by cultivation with o-dinitrobenzene. A cDNA library complementary to poly (A)+RNA of I. orientalis grown with o dinitrobenzene was screened by colony hybridization. Twenty positive clones were obtained from 6,000 clones and seven of twenty positive clones expressed glutathione S-transferase activity in E. coli. One of the expressing clones harboring plasmid pHT108 had 28 times more glutathione S-transferase activity induced by Isopropyl-beta-D-thio-galactopyranoside than a strain harboring plasmid pUC118. Expressed glutathione S-transferase Y-2 protein comigrated with yeast glutathione S-transferase Y-2 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as detected by immunoblot analysis. PMID- 2241961 TI - Protein kinase C and platelet inhibition by D-erythro-sphingosine: comparison with N,N-dimethylsphingosine and commercial preparation. AB - Sphingosine has been shown to be a potent and specific inhibitor of protein kinase C in vitro and in cell systems including human platelets. Questions have been raised as to the validity of commercial sphingosine as a protein kinase C inhibitor and whether sphingosine or N,N-dimethylsphingosine is the active species. In the present study, we compared the effects of synthetic D-erythro sphingosine, N,N-dimethylsphingosine and commercial sphingosine on purified protein kinase C in vitro and washed human platelets. These three compounds were found to be of high purity and well-defined structure based on [1H]NMR, FAB-mass Spectrometry, and TLC analysis. Both synthetic D-erythro-sphingosine and commercial sphingosine inhibited protein kinase C in vitro using vesicle as well as mixed micellar assays. N,N-dimethylsphingosine also significantly inhibited purified protein kinase C in vitro. Both preparations of sphingosine inhibited phosphorylation for 40 kD protein, a known substrate of protein kinase C in platelets. Similarly both sphingosine preparations inhibited aggregation and secretion of human platelets induced by 8 nM gamma-thrombin. These results indicate that sphingosine from commercial source, synthetic sphingosine and N,N dimethylsphingosine are equipotent in inhibiting protein kinase C. These studies also validate the utility of sphingosine as a phamarcologic inhibitor of protein kinase C in vitro and in cell systems. PMID- 2241962 TI - Specific interaction of a partially purified Xenopus transcription factor IIIC (TFIIIC) with frog tRNA gene. AB - Transcription factor IIIC (TFIIIC) from Xenopus has been partially purified and characterized. Footprinting analyses indicate that a partially purified TFIIIC fraction contains an activity which specifically recognizes the "B" block element of tRNA gene. In addition, two other regions located downstream from the "B" block sequence are also protected. Protection experiments on 5S genes by DNAase I with either TFIIIC alone or TFIIIA and TFIIIC produced a minimal change in the cleavage pattern implying that TFIIIC does not intimately associate with DNA. The implications of these findings in relation to the class III gene transcription are discussed. PMID- 2241963 TI - Spermine-like functions of N1, N12-bis(ethyl)spermine: stimulation of protein synthesis and cell growth and inhibition of gastric ulceration. AB - The spermine analogue N1, N12-bis(ethyl)spermine (BESPM) could mimic the functions of spermine in the following aspects: 1) BESPM could stimulate globin and ornithine decarboxylase synthesis in a rabbit reticulocyte cell-free system; 2) the addition of BESPM to the culture medium could recover cell growth of polyamine-deficient bovine lymphocytes; 3) spermidine uptake by bovine lymphocytes was inhibited by BESPM and spermine to a comparable degree; and 4) stress-induced gastric ulceration was inhibited by subcutaneous administration of BESPM. Since BESPM was less toxic than spermine for mice, BESPM or its derivatives may be useful for diseases which can be cured by polyamines. PMID- 2241964 TI - Recruitment of GLUT-4 glucose transporters by insulin in diabetic rat skeletal muscle. AB - The cause of reduced insulin-stimulated glucose transport in skeletal muscle of diabetic rats was investigated. Basal and insulin-stimulated glucose uptake into hindquarter muscles of 7-day diabetic rats were 70% and 50% lower, respectively, than in nondiabetic controls. Subcellular fractionation of hindquarter muscles yielded total crude membranes, plasma membranes and intracellular membranes. The number of GLUT-4 glucose transporters was lower in crude membranes, plasma membranes and intracellular membranes, relative to non-diabetic rat muscles. These results were paralleled by reductions in D-glucose-protectable binding of cytochalasin B. Insulin caused a redistribution of GLUT-4 transporters from intracellular membranes to plasma membranes, in both control and diabetic rat muscles. This redistribution was also recorded using binding of cytochalasin B. The insulin-dependent decrement in glucose transporters in intracellular membranes was similar for both animal groups, but the gain and final amount of transporters in the plasma membrane were 50% lower in the diabetic group. The results suggest that insulin signalling and recruitment of GLUT-4 glucose transporters occur in diabetic rat muscle, and that the diminished insulin response may be due to fewer glucose transporters operating in the muscle plasma membrane. PMID- 2241965 TI - Constitutive and inducible expression of human cytochrome P450IA1 in yeast Saccharomyces cerevisiae: an alternative enzyme source for in vitro studies. AB - A cDNA of human cytochrome P450IA1 was expressed in yeast Saccharomyces cerevisiae on a multicopy plasmid under the control of the constitutive GAPFL or the inducible PHO5 promoter. Microsomes of transformed yeast contained substantial amounts of the heterologous enzyme as determined by reduced CO difference spectra (156-68 pmol/mg). Enzyme kinetics with 7-ethoxyresorufin as substrate resulted in a Km value of 92 nM and a Vmax value of 223 pmol/mg/min, which is comparable to data obtained with human liver microsomes. The antimycotic drug ketoconazole (Ki = 22nM) as well as the isozyme specific P450 inhibitor alpha-naphthoflavone (Ki = 1.2 nM) were shown to be strong inhibitors of human P450IA1. Taken together, these data show that heterologous P450 gene expression in yeast is a potent instrument for the study of enzyme specific parameters and might be used to answer further questions with regard to substrate specificity as well as drug interaction in a background with no interfering activities. PMID- 2241966 TI - Endothelin-1 and U46619 potentiate selectively the venous responses to nerve stimulation within the perfused superior mesenteric vascular bed of the rat. AB - The effects were examined of endothelin-1 and U46619 on the responses to perivascular nerve stimulation of the simultaneously perfused arterial and venous vessels of the superior mesenteric arterial bed of the rat. Stimulation of the nerves at 4-16 Hz for 30 s caused frequency dependent constrictions of both the arterial and venous vessels similar to those produced by bolus doses of exogenous noradrenaline (0.1-10 nmol). Infusion of either endothelin-1 (0.1 nM) or U46619 (1-3 nM) caused small (less than or equal to 5 mmHg) increases in arterial and venous perfusion pressures and selectively potentiated the venous, but not arterial, responses to nerve stimulation. Conversely, endothelin-1 and U46619 potentiated the responses of both the arterial and venous vessels to exogenous noradrenaline. Thus, as reported previously for the arterial vessels of the rat mesentery, the isolated venous vessels constrict to perivascular nerve stimulation in a frequency dependent manner. In addition, endothelin-1 and U46619 potentiate selectively the effects of nerve stimulation on the veins. PMID- 2241967 TI - Interaction of insulin and phorbol esters on the regulation of DNA synthesis in rat hepatoma cells. AB - Insulin and phorbol esters stimulated DNA synthesis in rat H4 hepatoma cells. Insulin and phorbol ester induction of thymidine incorporation was dose dependent, with a maximal 4.2- and 3.0-fold increases at concentrations of 1 x 10(-9)M and 1 microM, respectively. Phorbol esters in combination with increasing concentrations of insulin resulted in additive effects, but only at submaximal insulin concentrations. The combination failed to increase thymidine incorporation above the maximal effects produced by insulin alone. When cells were pretreated with phorbol esters for 24h to produce protein kinase-C (PKC) deficiency, basal DNA synthesis was depressed. Pretreatment with phorbol esters abolished the effects of phorbol esters to induce DNA synthesis but did not impair the magnitude of insulin-induced DNA synthesis. Thus, although phorbol ester-activatable PKC-activity was necessary for basal DNA synthesis, it was not necessary for insulin-induction of DNA synthesis in H4 cells. PMID- 2241968 TI - Evidence for increased translational efficiency in the induction of P450IIE1 by solvents: analysis of P450IIE1 mRNA polyribosomal distribution. AB - The potential for enhanced translational processing of P450IIE1 mRNA during the early phase of P450IIE1 induction by pyridine or acetone was assessed by hybridization analysis of polyribosomal P450IIE1 mRNA distribution in rat hepatic tissue. Optical absorbance profiles of polyribosomal fractions exhibited an apparent shift at 5 h following pyridine administration relative to control. Slot and Northern blot analyses for P450IIE1 mRNA in the cytoplasmic extracts isolated from 5 h pyridine-treated rats demonstrated a shift in distribution of P450IIE1 message toward heavier polyribosomal fractions and Northern blot analysis suggested the presence of different populations of P450IIE1 mRNA. Slot blot analyses also demonstrated a shift in the polyribosomal distribution of P450IIE1 mRNA at 12 h following pyridine treatment; in contrast, hybridization analysis for P450IA1 revealed no shift in polyribosomal distribution of P450IA1 mRNA. Acute acetone administration to animals also resulted in a similar shift in polyribosomal distribution of P450IIE1 mRNA as compared to control. These data suggest that P450IIE1 mRNA shifts toward larger polyribosomes following acute exposure of animals to pyridine or acetone and provide evidence that induction of P450IIE1 at early times following acute pyridine or acetone administration involves enhanced translational efficiency through increased loading of ribosomes on P450IIE1 mRNA. PMID- 2241969 TI - Regulation of LH/hCG receptor by gonadotropins in rat ovary. AB - To investigate the regulation of the LH/hCG receptor gene by gonadotropins, we examined the effect of PMSG and hCG on the expression of LH/hCG receptor in immature rat ovary. Northern blot analysis of ovarian RNA revealed a major mRNA of 5400 nucleotides and minor species of 7500, 3600, 2300, and 1200 nucleotides, and PMSG treatment slightly increased the intensity of all LH/hCG receptor messengers. Subsequently, hCG treatment decreased the number of LH/hCG receptor by day 2 and mRNA levels by 12h after injection. The level of mRNA recovered and increased 5-fold of control by day 6, then returned to control levels by day 10, followed by slower decline in LH/hCG receptor in plasma membrane. These studies demonstrate that the effects of PMSG and hCG on the number of LH/hCG receptor are closely related to the actions of these hormones on LH/hCG receptor messenger levels. PMID- 2241970 TI - Functional interactions between phage T4 and E. coli DNA-binding proteins during the presynapsis phase of homologous recombination. AB - The "protein machine" for phage T4 homologous recombination has begun to be assembled in vitro. A particularly heavily studied reaction has been the uvsX protein (a RecA-like strand transferase)-mediated homologous pairing reaction between single and double-stranded DNAs, a key step in the recombination cycle in vivo. A necessary prerequisite for uvsX protein-mediated pairing is the polymerization of this factor along the invading single strand, a process known as presynapsis. Recent work has indicated that at least two other T4 recombination factors are involved in this process as well, the uvsY and gene 32 products. These proteins are also ssDNA-binding factors and exhibit an affinity for UvsX and each other. In order to begin to sort out the potential functional roles played by these protein-protein interactions in presynapsis, I have examined the ability of the uvsX protein to form stable filaments along ssDNA in the presence of these proteins. It is shown that the uvsY protein relieves the inhibition to filament formation due to the presence of the gene 32 protein, but experiments with the E. coli SSB protein (the bacterial analogue of gp32) suggest that this effect does not involve a direct interaction between UvsY and gp32. PMID- 2241971 TI - Inositol trisphosphate and thapsigargin discriminate endoplasmic reticulum stores of calcium in rat brain. AB - ATP dependent Ca2+ accumulation into oxalate-loaded rat brain microsomes is potently inhibited by thapsigargin with an IC50 of 2 nM and maximal inhibition at 10 nM. Approximately 15% of the total A23187-releasable microsomal calcium store is insensitive to thapsigargin concentrations up to 100 microM. Inositol-1,4,5 trisphosphate (IP3) maximally inhibits 40% of the net Ca2+ accumulation by whole brain microsomes. Its effects are non-additive with thapsigargin suggesting that the IP3-sensitive Ca2+ pool is a subset of the thapsigargin sensitive Ca2+ pool. Marked regional differences occur in Ca2+ transport rates and sensitivity to both thapsigargin and IP3. PMID- 2241972 TI - High concentrations of guanidine chloride activate lactate dehydrogenase in low water media. AB - The effect of guanidine chloride on the activity of bovine heart lactate dehydrogenase transferred to a system that was made with toluene, phospholipids, Triton X-100 and 3.8% water (v/v) was studied. The activity of the enzyme in the latter system was about 30 times lower than in standard water mixtures. In the low water system, 1.5 and 2.0 M guanidine chloride increased the activity by approximately 20 times. These concentrations of guanidine chloride caused complete inactivation of the enzyme in conventional water systems. The activating effect of the denaturant was independent of enzyme concentration. It is suggested that the increase in activity produced by guanidine chloride was due to a facilitation of the protein-solvent interactions that operate in a catalytic cycle. PMID- 2241973 TI - Identification of a naturally occurring methyl-ester of phosphate, methyl phosphorylcholine (methyl-2-(N,N,N trimethylamino) ethyl phosphate), in the eggs of the sea urchin S. purpuratus. AB - A novel metabolite of choline, phosphorylcholine methyl ester, has been identified in the eggs of S. purpuratus wherein it is present at approximately 1 mM concentration. To the best of our knowledge, this is the first instance of a phosphoryl-methyl-ester to be observed in nature. The compound appears to be species specific, since it has not been observed in other species such as L. pictus and P. depressus. In S. purpuratus its distribution is confined to the ovary, eggs and embryos, and is absent from young animals following metamorphosis. PMID- 2241974 TI - Conformation of proline residues in bacteriorhodopsin. AB - Proline, noted as a hydrophilic residue with helix-breaking potential, nevertheless occurs widely in putatively alpha-helical transmembrane segments of many transport proteins. Ligand-activated or enzyme-assisted trans/cis isomerization of an X-proline peptide bond (where X = any amino acid)--a dynamic, reversible event which could alter the orientation of a transmembrane alpha-helix -may provide the molecular basis for a protein channel regulatory process. Further elucidation of such a function requires knowledge of the isomeric status of the X-Pro bonds in native conformations of membrane proteins. We have used 13C nuclear magnetic resonance (NMR) spectroscopy to examine the conformation of intramembranous X-Pro peptide bonds in biosynthetically-labelled samples of a model transport protein, bacteriorhodopsin (bR) (purple membrane). Spectra of 13C Tyr-carbonyl labelled bR (in the solvent system CHCl3:CD3OD (1:1) + 0.1 M LiClO4) first established that all 11 bR Tyr residues were sufficiently mobile for their resonances to be detected and resolved, independent of their domain location within the bR sequence. By taking advantage of the known diagnostic chemical shifts of the isomers of Pro-C gamma carbon resonances, spectra of bR labelled with 13C gamma-Pro were then used to demonstrate that all 11 bR X-Pro peptide bonds--including those within the protein's membrane domain (Pro50, Pro91, Pro186)--are in the trans conformation in resting state bR. PMID- 2241975 TI - Retinoic acid inhibits the myristoylation of a membrane protein in HL-60 cells. AB - Incubation of nondifferentiated HL-60 cells with high specific activity myristic acid results in myristoylation of a 25 KD membrane protein. Myristoylation was inhibited by retinoic acid but not by DMSO, thus indicating that the nonmyristoylated state induced by retinoic acid is causal to rather than the result of the overall differentiation sequel induced. Similarly, incubation of HL 60 cells with high specific activity retinoic acid results in specific retinoylation of a membrane protein of similar molecular mass. The two acylated proteins could however be separated by 2-D gel electrophoresis, thus indicating that inhibition of myristoylation by retinoic acid could not be accounted for by competition between retinoic and myristic acids for the same acylated site. PMID- 2241976 TI - Analysis of big endothelin-1 digestion by cathepsin D. AB - Digestion of big endothelin (ET)-1 by cathepsin D, which is the only substantially identified protease showing ET converting enzyme activity, was characterized. Increased doses of cathepsin D showed decrease of immunoreactive (ir-) ET produced from big ET-1. Time course of big ET-1 conversion showed marked increase of ir-ET in a relatively short period, but further incubation resulted in the decrease of ir-ET. Incubation at various pHs with different doses of cathepsin D revealed that low doses of cathepsin D yielded the maximum production of ir-ET at pH 3.5-4.0, but higher doses of cathepsin D showed a bimodal curve of ir-ET production, which may be due to degradation of ir-ET. HPLC analysis revealed that cathepsin D cleaves Asn18-Ile19 bond in addition to Trp21-Val22 bond of big ET-1. These data suggests cathepsin D is not a physiological endothelin converting enzyme. PMID- 2241978 TI - Identification of a novel platelet-derived neutrophil-chemotactic polypeptide with structural homology to platelet-factor 4. AB - A novel protein, NAP-4, could be isolated from human platelet lysates. NAP-4 preparations induced chemotaxis of human neutrophils with an ED50 near 400 ng/ml. Purification by anti NAP-1/IL-8 affinity chromatography and reversed phase HPLC revealed a single peak showing a single line upon SDS-PAGE corresponding to a Mr of 8000. NH2-terminal sequence analysis indicated an unique sequence showing strong homology to human platelet factor 4 and weak homology to tumor necrosis factor alpha as well. The most interesting finding is the absence of the first two cysteins, known to be strongly conserved in members of the family of platelet factor 4-like host defense cytokines. PMID- 2241977 TI - The triterpene celastrol as a very potent inhibitor of lipid peroxidation in mitochondria. AB - The inhibitory effect of the dienone-phenolic triterpene, celastrol, on lipid peroxidation in rat liver mitochondrial membranes induced by ADP and Fe2+ was studied. The anti-peroxidative effect of celastrol was very strong: its 50% inhibitory concentration was 7 microM, and it was about 15 times more effective than alpha-tocopherol. Celastrol scavenged 1.5 molar equivalents of radicals in homogeneous aqueous ethanolic solution, whereas cysteine and alpha-tocopherol scavenged one and two molar equivalents of radicals, respectively. The process of anti-peroxidation of celastrol was biphasic, possibly due to stepwise inhibitions of peroxidation in the outer and inner mitochondrial membranes. PMID- 2241979 TI - Myristoylation of heparan sulfate proteoglycan and proteins occurs post translationally in human colon carcinoma cells. AB - We have recently shown that the heparan sulfate proteoglycan of human colon carcinoma cells is acylated with both myristate and palmitate, two long-chain saturated fatty acids. In this study we show that cycloheximide did not significantly inhibit the incorporation of myristic acid into either proteoglycan or total protein pool. This lack of inhibition occurred under a condition in which protein synthesis was inhibited greater than 90%. Cycloheximide, on the other hand, did not affect the incorporation of [3H]myristic acid into fatty acid nor the intracellular interconversion of myristate to palmitate. Characterization of fatty acyl moiety in the proteoglycan and protein by reverse-phase HPLC revealed that approximately 60% of the covalently bound fatty acids was myristate and the remaining 40% was palmitate. These results indicate that in human colon carcinoma cells myristoylation of heparan sulfate proteoglycan and proteins occurs post-translationally, presumably in the Golgi complex. PMID- 2241980 TI - Purification of Trypanosoma cruzi surface proteins involved in adhesion to host cells. AB - We have identified four surface 83 kDa proteins of pI values 6.3, 6.4, 6.5 and 6.6 in T. cruzi trypomastigotes which specifically bind to rat heart myoblasts. These proteins were purified by isoelectric focusing and anion-exchange chromatography in an FPLC system. These 83 kDa proteins inhibit the attachment of trypomastigotes to myoblasts in a concentration-dependent manner, indicating that these trypomastigote proteins mediate the attachment of trypomastigotes to heart myoblasts. PMID- 2241981 TI - High concentration of inositol 1,4,5-trisphosphate in sea urchin sperm. AB - We measured inositol 1,4,5-trisphosphate (InsP3) content of sea urchin gametes by using a specific protein binding assay, and found that a spermatozoon contains 4 x 10(-19) to 1 x 10(-18) moles of InsP3 before the acrosome reaction. Since the acrosome reaction has previously been shown to increase the InsP3 content of sperm severalfold, our measurement indicates that a spermatozoon contains at least 2 x 10(-18) moles of InsP3 at fertilization, corresponding to a concentration in the spermatozoon of about 1 mM. The threshold for activation of eggs by injection of InsP3 dissolved in a much larger volume of solution has been found to be about 3 x 10(-18) moles, corresponding to a concentration in the injectate of 1 microM. This suggests that sea urchin sperm may contain enough InsP3 to activate eggs. With an electroporation method, we also showed that sperm extract acts on eggs only from inside, consistent with a primary messenger role for InsP3. PMID- 2241982 TI - Effect of ATP depletion and phenanthroline on the spermidine-mediated decay of ornithine decarboxylase in erythroleukemia cells. AB - Addition of spermidine to Friend erythroleukemia cells caused a rapid decay of ornithine decarboxylase (ODC) activity and the accumulation of a ODC-antizyme complex. The induction of antizyme only partially accounted for the decrease of ODC activity by a direct inhibition of the enzyme. However, the antizyme induction was accompanied by a marked reduction of the half-life of ODC. Shift of the cells to an ATP-depleting medium prevented the spermidine-elicited decay of ODC activity as well as the accumulation of ODC-antizyme complex. However, ODC appeared to be stabilized even when ATP depletion was performed 40 min after spermidine addition, in the presence of high levels of antizyme. Similar results were obtained by treating the cells with phenanthroline, a heavy metal chelator and protease inhibitor. These findings indicate that ATP and some metalloprotease(s) may be involved in the degradation pathway of ODC, even in the presence of high levels of polyamines. PMID- 2241983 TI - Transforming growth factor beta regulates cystatin C in serum-free mouse embryo (SFME) cells. AB - Differential screening of a cDNA library derived from mRNA of TGF beta-treated serum-free mouse embryo (astrocyte precursor) cells isolated a strongly TGF beta regulated mRNA that codes for cystatin C, a cysteine protease inhibitor. Increase in cystatin C mRNA level was observed within four hours after treatment with picomolar concentrations of TGF beta. The increase was reversible upon removal of TGF beta and was not prevented by cycloheximide. These results suggest that cystatin C expression may represent a developmentally regulated differentiated function of astrocytes, and also suggest that cystatin C expression may be involved in the response of brain cells to platelet release of TGF beta after trauma or injury. PMID- 2241984 TI - Anti-oxidant property of ethanolic extract of propolis (EEP) as evaluated by inhibiting the chemiluminescence oxidation of luminol. AB - Ethanolic extract of propolis (EEP) has remarkable medical properties, including protection of mice against gamma irradiation. Its anti-oxidative effect has been attributed to its radical scavenging ability. This manuscript demonstrates the ability of increasing amounts of EEP to inhibit luminol-H2O2 chemiluminescence in vitro, and suggests that its anti-oxidative capacity is partly due to its high content of flavonoids. PMID- 2241985 TI - Increased lipid peroxidation in kidney of vitamin B-6 deficient rats. AB - Lipid peroxidation in kidney of rats fed with vitamin B-6 deficient diet for a period of 12 weeks was studied with pair-fed controls. The basal lipid peroxide level as well as the degree of susceptibility to lipid peroxidation in presence of promotors such as NADPH, ascorbate, t-butyl hydroperoxide, Fe2+, Cu2+ and oxalate, were increased in vitamin B-6 deficient kidney. The observed increased lipid peroxidation in vitamin B-6 deficient kidney was correlated with high levels of lipids, copper, iron, calcium and oxalate, low levels of antioxidants and antioxidant enzymes and increased levels of hydroperoxides and hydroxyl radicals. PMID- 2241986 TI - Mechanism of polyamine spermidine uptake by Xenopus laevis oocytes. AB - In this study, the mechanisms of polyamine spermidine (Spd) uptake were investigated in Xenopus laevis oocytes. Spd uptake followed a sigmoidal kinetics with [S]90/[S]10 = 3 microM and Hill interaction coefficient (n) = 2. The order of magnitude of uptake and efflux was similar (t1/2 = 45 min). The equilibrium potential for Spd, calculated by Nenrst equation, was 90.78 mV. Free energy change for the uptake (delta G) was found to be 2.31 Kcal/mole of Spd. During efflux, Spd was not converted into putrescine or spermine. It seems that there are two types of Spd uptake pathways: Na(+)-dependent and Na(+)-independent since replacement of Na+ from incubation medium did not completely abolish the Spd uptake. The Na(+)-dependent component of Spd uptake was shared neither by system A nor by system ASC amino acids. PMID- 2241987 TI - Purification and properties of pyruvate kinase from Dictyostelium discoideum. AB - Pyruvate kinase (EC 2.7.1.40) from aggregating Dictyostelium discoideum cells has been purified to homogeneity. It has a monomeric molecular weight of 66kD and is tetrameric in low ionic strength buffers. The enzyme is not regulated by fructose 1,6-bisphosphate or by alanine and appears to resemble the M1 isoenzyme from rat liver most closely, although its activity is not inhibited by ATP. PMID- 2241988 TI - Action of catalase on peroxyacetic acid. Kinetic studies. AB - The activity of catalase on peroxoacetic acid was studied by a kinetic point of view. The "inactivation-reactivation" sequence consists in two first order (intramolecular) one-electron redox reactions. In the catalytic cycle, the reaction producing Compound I is, as espected, a second order process rate determined by the enzyme-peroxide adduct formation step, whereas, surprisingly, the reaction restoring the enzyme resting state is a first order process in which the limiting step is the 0-0 linkage breaking inside the Compound I-peroxide adduct. PMID- 2241989 TI - Microfilament gel rigidity cooperates negatively with the binding of actin gelling proteins. AB - At 37 degrees C, in the presence of 0.1 M KC1 and 2 mM MgCl2, the binding of alpha-actinin to F-actin increases with the concentration of alpha-actinin but not with the concentration of F-actin. This implies that binding is determined by additional factors, beside the alpha-actinin - F-actin association constant. We propose that one of these factors is the rigidity of the gel, which cooperates negatively to the binding by increasing the work needed to bring two actin filaments at the reaction distance with alpha-actinin. PMID- 2241990 TI - Isolation and characterization of non-muscle tropomyosin cDNAs of human and mouse origin. AB - Several cDNA clones of human and mouse non-muscle tropomyosin have been isolated. All the human clones possess a common 23 bp sequence immediate 5' of the initiation codon. However, in the further upstream regions, the nucleotide sequences diverge. Two of the mouse cDNA clones pPSI-8 and pPSI-14 have identical nucleotide sequence in the coding region sequenced. However, 5' of the initiation codon these clones have only 40 identical nucleotides and further upstream the nucleotide sequences diverge. Analysis of the genomic DNAs of mouse cells indicated the possibility of a common gene giving rise to both the tropomyosin cDNAs differing in their 5' ends. PMID- 2241992 TI - Maturation-specific type II cyclic AMP-dependent protein kinase in goat sperm plasma membrane. AB - Highly purified plasma membranes (PMs) isolated by aqueous two-phase polymer methods from goat sperm undergoing epididymal maturation, have been analyzed for the isoenzymes of cyclic AMP-dependent protein kinase (RC). The mature and the immature spermatozoa showed profound differences in the profile of the isoenzymes of RC solubilized from the isolated PMs with 0.1% Triton X-100. The immature sperm PM consists of only type I RC in contrast to the mature sperm membrane which possesses both the type I and II isoenzymes. The type II kinase represents nearly 30% of the total membrane-bound RC of the mature cells. The analysis of the surface topography of these isoenzymes of the maturing spermatozoa by using diazonium salt of sulfanilic acid as the surface probe shows that the PM-bound RC(s) are oriented primarily on the external surface of these intact cells. The data demonstrate that type II RC is a maturation-specific ecto-kinase as it appears on the sperm surface specifically during the maturation of spermatozoa in the epididymis. PMID- 2241991 TI - Decrease of liver protein kinase C in streptozotocin-induced diabetic rats and restoration by vanadate treatment. AB - Effects of streptozotocin-induced diabetes and administration of the insulinmimetic agent, vanadate in rats on the liver protein kinase C-induced phosphorylation of exogenous C (Histone III-S) and endogenous substrates were investigated. Diabetes caused a significant fall (40-60%) in liver cytosolic protein C activity measured using both types of substrates. Vanadate treatment for a period of 5 weeks restored them to normal levels. Phosphorylation of cytosolic target proteins for protein kinase C followed a similar pattern in response to diabetes and vanadate. These treatments had no effect on particulate protein kinase C activity. Vanadate also had no effect in normal livers with respect to the protein kinase C system. PMID- 2241993 TI - Purification and characterization of high salt-soluble vicilin from mung bean (Vigna radiata). AB - We report a method for the purification of vicilin from mung bean (Vigna radiata) mainly on the basis of solubility of mung bean vicilin even in high salt. Mung bean vicilin remains in solution even after 90% relative saturation of ammonium sulphate. The resulting supernatant after dialysis was subjected to gel filtration (Sephadex G-150) to remove other contaminant polypeptides, and finally the protein was purified by DEAE cellulose chromatography. This purified fraction exhibited 3 bands on SDS-PAGE compared with vicilin from other legumes which exhibite more than 3 bands generally. The results raise the possibility that the presence of the two small polypeptides in vicilin preparations is the breakdown product of the major larger one of mol.wt. 52 K and that vicilin may be a tetramer of four subunits of Mr 52000. That the high salt-soluble protein containing 52 K subunit is vicilin has been determined by several criteria. PMID- 2241994 TI - Multiple forms of adenylate kinase in pig brain. AB - The rate of ATP formation from ADP by adenylate kinase is known to be easily followed by determination of the increase in fluorescence due to the NADPH that is formed by combined reactions of hexokinase and gluc-6-p dehydrogenase. We found that the rate of CTP formation from CDP also can be followed similarly by use of more units of hexokinase and extension of the reaction time. A crude enzyme sample containing most of the activity of adenylate kinase was prepared from pig brain and eluted from a CM-cellulose column. Enzymatic activity of ATP formation and that of CTP formation were compared for all the fractions. Two fractions were found in the eluate; one was rather specific for ADP as substrate, and the other was less specific for ADP and could form CTP at an appreciable rate. PMID- 2241995 TI - Polyclonal antibodies against rat liver cytosolic casein kinase II (CK-2) cross react with CK-2 from other tissues and nuclear form (PK-N2) of the enzyme. AB - Casein kinase II (CK-2) is a ubiquitous serine/threonine protein kinase, and is localized to both the cell nucleus and cytoplasm. Despite extensive biochemical similarities in their properties, there is evidence that the two forms of the enzyme exhibit certain distinctions (1). This prompted us to produce antibodies against CK-2, which could be utilized as a possible tool for investigations of the various forms of this enzyme. Specific polyclonal antibodies against the rat liver cytosolic CK-2 were raised in egg yolk of laying hens; the enzyme had repeatedly failed to elicit an immunogenic response in rabbits. The purified polyclonal antibody (egg yolk immunoglobulin, IgY) recognized all three subunits (42, 38, and 28 kDa) of the enzyme in immunoblots. The antibody when bound to a matrix was capable of removing CK-2 from solution, and the bound enzyme could be recovered from the immunoaffinity matrix with 0.1 M diethylamine. The antibody exhibited a high affinity towards CK-2 prepared from cytosol of liver, ventral prostate, and several other rat tissues, but no immunoreactivity was detected towards a number of other protein kinases tested. The subunits of the nuclear form of CK-2 (PK-N2) migrated differently when electrophoresed in parallel in the same gel. However, the antibody did cross-react with the various subunits of PK N2 suggesting a significant homology in the immunogenic domains in the various subunits of the two forms of the enzyme. PMID- 2241996 TI - Chemical modification reveals involvement of tyrosine in ligand binding to dopamine D1 and D2 receptors. AB - The effect of tyrosine-alkylating agents on the ligand-binding properties of bovine striatal dopamine D1 and D2 receptors was investigated. The tyrosine alkylating agents, p-nitrobenzenesulphonylfluoride (pNBSF) and tetranitromethane (TNM) caused a time-and dose-dependent loss of the binding of [3H]SCH-23390 and [3H]spiroperidol, ligands specific for dopamine D1 and D2 receptors, respectively. The two dopamine receptors, however, showed a differential sensitivity to inactivation by these agents. The mechanism of inhibition of the two receptors appears to be complex as treatment of membranes with pNBSF and TNM resulted in a decrease of both the Kd and the Bmax of ligand binding. Spiroperidol almost completely protected the TNM-induced inhibition of [3H]spiroperidol binding to dopamine D2 receptors whereas SCH-23390 afforded only partial protection of the [3H]SCH-23390 binding by TNM suggesting that more than one tyrosine groups may be involved in the D1 receptor binding activity. PMID- 2241997 TI - Inhibition of arylhydrocarbon hydroxylase and cytochrome P-450 by 20 methylcholanthrene and phenobarbital in guinea pig on excessive doses of ascorbic acid. AB - Treatment of guinea pigs on adequate ascorbic acid (AA) with 20 methylcholanthrene (MCA) and phenobarbital (PB) significantly increased hepatic arylhydrocarbon hydroxylase (AHH), cytochrome P-450 and cytochrome-b5 activities. In lungs, only MCA treatment significantly enhanced the activities of AHH, cytochrome P-450 and cytochrome b5. In animals on excessive doses of AA, there was inhibition of hepatic AHH, cytochrome P-450 and cytochrome b5 levels by treatment with these xenobiotics. Also, inhibition was observed in pulmonary AHH and cytochrome P-450 levels. The relevance of these observations in excessive AA fed guinea pigs to carcinogenesis requires further extensive investigations. PMID- 2241998 TI - Changes in erythrocyte glutathione peroxidase and glutathione reductase in alloxan diabetes. AB - Glutathione peroxidase and glutathione reductase activities were measured in erythrocytes from control, diabetic and insulin-treated diabetic rats. A significant decrease in the activity of glutathione peroxidase and an increase in the glutathione reductase activity were found with increase in the time of diabetes which may result in the alteration in the activity of the pentose phosphate pathway by the modulation of the levels of NADPH. Insulin administration reverses the change in the activity of glutathione peroxidase but does not reverse the glutathione reductase activity during diabetes. The overall changes may be due to changes in the levels of insulin, triiodothyronine and thyroxine. PMID- 2241999 TI - Fatty acid uptake and catecholamine-stimulated phospholipid metabolism in immortalized airway epithelial cells established from primary cultures. AB - The incorporation of [14C]oleic and [14C]linoleic acid into phospholipids and neutral lipids was compared in two recently immortalized airway epithelial cell lines. In addition, the effects of adrenergic stimulation on phospholipid turnover was examined. Both cell lines readily incorporated the fatty acids into all phospholipid and neutral lipid fractions. Isoproterenol (1 microM) induced Ca2+ transients in both cell lines, indicating a functional beta-adrenergic response. Epinephrine (10 microM; 15 min) stimulation of cells prelabeled with [14C]linoleic acid increased the percentage of label in phosphatidylcholine in one cell line. Lipid metabolism can now be extensively studied in human airway epithelia. PMID- 2242000 TI - Use of a hapten specific anti-dansyl antibody for the localization of ribosomal proteins by immuno electron microscopy. AB - The fluorescent reagent dansyl chloride has been used as an immunological marker for the electron microscopic localization of ribosomal proteins on the surface of 50S ribosomal subunits. The proteins BstL1 from Bacillus stearothermophilus and EcoL1 from Escherichia coli were dansylated to various degrees and reconstituted into the L1-deficient E. coli 50S subunits from mutant MV17-10. Using antibodies specific to dansyl chloride, both proteins were mapped at the lateral protuberance near the peptidyl transferase center. PMID- 2242001 TI - Biogenic amine binding sites in rabbit spermatozoa. AB - The binding of the neuroleptic, [3H] spiperone, to rabbit spermatozoa was investigated. Binding was partially inhibited by haloperidol, mianserin or epinephrine. Mixtures of two of the three inhibitors reduced binding further, but binding of the radioligand to spermatozoa was lowest in the presence of all three inhibitors. Unlabeled spiperone eliminated binding. Cholinergic ligands, GABA, and beta-adrenergic ligands, had little effect on binding. Spiperone binding occurred to both heads and tails suggesting that alpha 1-adrenergic, D2-dopamine and S2-serotonin binding sites are present in the head and/or tail of rabbit spermatozoa. PMID- 2242002 TI - Phorbol esters augment spermidine transport without protein kinase C activation. PMID- 2242003 TI - Histamine as an intracellular messenger. PMID- 2242004 TI - Regulation of the adhesion of neutrophils to endothelium. PMID- 2242005 TI - Isoelectric focusing of isoenzymes of monkey platelet monoamine oxidase. AB - Monkey platelet monoamine oxidase (MAO) was preferentially found as the B-form of the enzyme as observed from differences in substrate specificities, as well as liver MAO. The isoelectric points and molecular weights of platelet MAO subunits were compared with those of monkey liver using sodium dodecyl sulfate-disc polyacrylamide gel electrophoresis and isoelectric focusing-disc gel electrophoresis. The pI value of monkey liver was a single peak at 6.5, but the pI values of monkey platelets were triple peaks at 5.5, 6.5 and 7.0. The molecular weight of MAO subunits in monkey platelets was similar to that of liver, and was found to be about 60,000. These results indicate that MAO-B of monkey platelets differs from MAO-B of the liver, and that it has different electrophoretic properties. PMID- 2242006 TI - On the mechanism of sodium 2-5-4 chlorophenylpentyloxirane-2-carboxylate (POCA) inhibition of hepatic gluconeogenesis. AB - Inhibition of hepatic long chain fatty acid oxidation by 2-5-4 chlorophenylpentyloxirane-2-carboxylate (POCA) leads to decreased gluconeogenic rates from lactate or from low concentrations of pyruvate. The inhibitory effect is fully overcome by concentrations of pyruvate above 0.8 mM or by the simultaneous administration of a medium chain fatty acid. At low pyruvate availability the energy cost of gluconeogenesis is mainly supported by fatty acid oxidation and POCA-induced inhibition of glucose production is secondary to a decreased energy availability. This is supported by the following observations: (i) POCA decreases hepatic respiration and phosphorylation potential: (ii) the rate of pyruvate-induced respiration was the same regardless of whether gluconeogenesis was inhibited or not by POCA: and (iii) concentrations of pyruvate above 0.8 mM, at which gluconeogenesis is not inhibited, prevented the POCA-induced decrease in the phosphorylation potential. It is concluded that inhibition of long chain fatty acid oxidation by POCA leads to a switch of energy fuel, and results in the oxidation of more pyruvate to meet the cellular energy demands. When pyruvate availability is low and thus, presumably, its mitochondrial transport restricted, pyruvate carboxylation most probably becomes limiting as a result of the increased flux through pyruvate dehydrogenase, in the presence of POCA. PMID- 2242007 TI - Phase I and phase II xenobiotic biotransformation in cultures and co-cultures of adult rat hepatocytes. AB - The aim of this study was to measure the activity of phase I and II key enzymes in the biotransformation of xenobiotics and their inducibility by phenobarbital (2 mM) in two currently used in vitro models, namely adult rat hepatocytes, conventionally cultured or co-cultured with rat epithelial cells derived from primitive biliary duct cells. For phase I, the cytochrome P450 content and the enzymic activities of 7-ethoxycoumarin O-deethylase and aldrin epoxidase have been determined, for phase II glutathione S-transferase activity was measured. In conventional cultures, all phase I parameters investigated declined continuously as a function of culture time. Two mM phenobarbital had inducing effects on 7 ethoxycoumarin O-deethylase and glutathione S-transferases but not on aldrin epoxidase. In co-cultures, after an initial decrease, a steady state situation developed for all the parameters measured, lasting for at least 10 days. The cytochrome P450 content, the 7-ethoxycoumarin O-deethylase, aldrin epoxidase and glutathione S-transferase activities were maintained from 3 to 4 days on at 25, 100, 15 and 50%, respectively, of their corresponding value obtained for freshly isolated hepatocytes. After phenobarbital treatment, the parameters mentioned were significantly increased with the exception of the aldrin epoxidase activity of which the inducibility was nearly completely lost. PMID- 2242009 TI - The dispositional enantioselectivity of indobufen in rat and mouse. AB - The plasma pharmacokinetics and urinary elimination of the enantiomers of indobufen, a novel platelet aggregation inhibitor, have been studied in rats and mice given either the racemic compound or the individual enantiomers (rat 8 mg/kg racemate, 4 mg/kg enantiomers; mouse 25 mg/kg racemate, 12.5 mg/kg enantiomers). Enantiospecific analysis of indobufen in plasma and urine was achieved by HPLC of its L-leucinamide diastereoisomers. In rat, the two enantiomers have very different plasma elimination half lives (S, 3.9 hr; R, 12.2 hr), irrespective of the optical form administered. The plasma concentration-time curves of S indobufen were identical after racemic or S-indobufen, but the plasma levels of R indobufen were lower after the R-enantiomer than after the racemate. Urinary recovery of free and conjugated indobufen was less than 3% of the dose, independent of the optical form administered. In the mouse, R-indobufen was cleared from plasma more rapidly than its S-antipode (elimination T1/2 R, 2.5 hr; S, 3.8 hr) but differences were smaller than those seen in the rat. The plasma concentration-time curves of the S-enantiomer were the same after racemic or S indobufen, but levels of its R-antipode were much lower when it was given alone than after administration of the racemate. The urinary recovery of free and conjugated indobufen also exhibited enantioselectivity, with preferential elimination of the S-enantiomer. PMID- 2242008 TI - R 76713 and enantiomers: selective, nonsteroidal inhibitors of the cytochrome P450-dependent oestrogen synthesis. AB - The triazole derivative, R 76713 and its enantiomers R 83839(-) and R 83842(+) are effective inhibitors of the aromatization of androstenedione. For human placental microsomes, the (+) enantiomer (R 83824) is about 1.9- and 32-times more active than the racemate (IC50 2.6 nM) and the (-) enantiomer, respectively. R 83842 is about 30- and 1029-times more active than 4-hydroxyandrostene-3,17 dione and aminoglutethimide. This potency might originate from its high affinity for the microsomal cytochrome P450 (P450). Indeed, R 83842, compared to R 76713 and R 83839, forms a more stable P450-drug complex. Difference spectral measurements indicate that the triazole nitrogen N-4 coordinates to the haem iron. The reversed type 1 spectral changes suggest that R 76713 is able to displace the substrate from its binding place and the stable complex formed in particular with the (+) enantiomer suggests that its N-1-substituent occupies a lipophilic region of the apoprotein moiety. Kinetic analysis implies that there is a competitive part in the inhibition of the human placental aromatase by R 76713. The Ki values for R 76713, R 83842 and R 83839 are 1.3 nM, 0.7 nM and 18 nM, respectively. These results are indicative of stereospecificity for binding. Up to 10 microM, R 76713 and its enantiomers have no statistically significant effect on the regio- and stereoselective oxidations of testosterone in male rat liver microsomes. All three compounds have no effect on the P450-dependent cholesterol synthesis, cholesterol side-chain cleavage and 7 alpha-hydroxylation and 21-hydroxylase. At 10 microM, R 76713 has a slight effect on the bovine adrenal 11 beta-hydroxylase. This effect originates mainly from R 83839, the less potent aromatase inhibitor. On the other hand, the inhibition of the 17,20-lyase of rat testis observed at concentrations greater than or equal to 0.5 microM, originates rather from R 83842. However, 50% inhibition is only achieved at 1.8 microM R 83842, i.e. at a concentration about 1300-times higher than that needed to reach 50% inhibition of the human placental aromatase. PMID- 2242010 TI - Hepatic subcellular localization of cresylbenzodioxaphosphorin oxide (CBDP) sensitive soman binding sites. AB - The toxicity of the organophosphorus poison soman (pinacolylmethylphosphonofluoridate) is attributable to its irreversible inhibition of the enzyme acetylcholinesterase. In addition, soman binds irreversibly to a number of noncholinesterase tissue binding sites which appear to be its major means of in vivo detoxification. This study was conducted to determine the hepatic subcellular localization of these sites. Subcellular fractions of liver from male Sprague-Dawley rats (200-250 g) were prepared by differential and isopycnic density gradient centrifugation. The binding of [14C]soman to these subcellular fractions was determined in the presence and absence of cresylbenzodioxaphosphorin oxide (CBDP), a compound that binds irreversibly to the noncholinesterase soman binding sites. Crude fractionation of liver homogenates into nuclear, mitochondrial, microsomal, and soluble fractions revealed that 78% of the total CBDP-sensitive binding activity was localized in the nuclear and microsomal fractions. Further purification of these fractions indicated that all of the homogenate binding activity could be accounted for in the purified microsomal fraction. When purified liver microsomes were solubilized and fractionated on linear sucrose gradients, 90% of the CBDP-sensitive soman binding activity cosedimented with carboxylesterase activity which suggests that these binding sites are carboxylesterase. PMID- 2242011 TI - Metabolism of nicotine by hepatocytes. AB - The profile of nicotine metabolites produced by freshly isolated hepatocytes from rats, hamsters, guinea pigs, mice and humans was investigated after a 30-min exposure to nicotine ([2-14C]pyrrolidine). Large species differences occurred in the extent of nicotine metabolism; these ranged from 95% metabolism in guinea pig hepatocytes to only 30% metabolism in human and rat hepatocytes. The spectrum of metabolites formed also varied widely in different species. In hepatocytes from obese human subjects, nicotine was metabolized most extensively in smokers, least in nonsmokers, and to an intermediate degree in exsmokers, suggesting that cigarette smoking enhances the rate of nicotine metabolism. Pretreatment of all nonhuman species studied with phenobarbital and beta-naphthoflavone and with Aroclor in rats produced distinctive inductive patterns. Phenobarbital pretreatment of nonsmokers for 2 days prior to liver biopsy doubled the extent of nicotine conversion to cotinine by their hepatocytes. Rat and hamster hepatocytes exhibited sex and stereoselectivity differences in nicotine metabolism. Collectively, these studies indicate that hepatocytes offer some advantages over in vivo systems in investigating certain aspects of nicotine metabolism. PMID- 2242012 TI - Differential effects of daily administration of cocaine on hepatic and cerebral glutathione in mice. AB - Twenty-four hours after acute administration of cocaine HCl (25 mg/kg, i.p.) to male C57BL/6ByJ mice, there was no hepatotoxicity as measured by plasma aspartate aminotransferase (AST) activity. In contrast, daily administration of cocaine (25 mg/kg, i.p.) for 14 days induced marked hepatotoxicity, as characterized by a greater than 400% increase in plasma AST activity when assayed 24 hr after the last injection. Concomitantly, the liver had increased levels of cysteine, gamma glutamylcysteine, glutathione, cysteinylglycine, glutamate, methionine, taurine, and aspartate. The effect appeared to be selective for compounds of the glutathione metabolic pathways, because repeated cocaine exposure did not affect other amino acids such as leucine, isoleucine, phenylalanine, serine, and valine. There was a positive correlation between the magnitude of the elevation of cysteine and the extent of liver damage. Daily cocaine administration did not affect striatal or frontal cortex glutathione. A final cocaine challenge (50 mg/kg, i.p.) did not affect either hepatic or cerebral glutathione metabolism. The increase in hepatic cysteine and glutathione upon daily cocaine administration is a potentially important compensatory mechanism against cocaine induced hepatotoxicity. PMID- 2242013 TI - Acute effect of thyroid hormone on insulin secretion in rats. AB - To elucidate the mechanism of thyroid hormone-induced hyperinsulinemia, the acute and direct effect of thyroid hormone administration on insulin secretion was investigated in rats in vivo and in vitro. In the perfused rat pancreas, the addition of thyroxine (10 micrograms/dL) or 3,5,3'-triiodothyronine (150 ng/dL) to the perfusing medium did not affect insulin secretion. The administration of thyroxine (40 micrograms/kg, s.c.) in vivo increased the plasma insulin level from 11 +/- 2 microUnits/mL (mean +/- SD) to 30 +/- 7 microUnits/mL, while blood glucose and plasma glucagon were unchanged. This phenomenon was inhibited completely by the preadministration of oxprenolol hydrochloride (2 mg/kg, s.c.), and inhibited partly by the preadministration of metoprolol tartrate (35 mg/kg, s.c.). These results suggest that thyroid hormone induces hyperinsulinemia via beta-adrenergic stimulation in the rat. PMID- 2242014 TI - Inhibition of ribonucleotide reductase and growth of human colon carcinoma HT-29 cells and mouse leukemia L1210 cells by N-hydroxy-N'-aminoguanidine derivatives. AB - A series of N-hydroxy-N'-aminoguanidine (HAG) derivatives were studied and compared for their effects on ribonucleotide reductase activity in cell-free extracts; on nucleic acid synthesis and the growth of human colon carcinoma HT-29 cells; and on mouse leukemia L1210 cells in culture. The HAG derivatives [RCH=NNHC(=NH)NHOH-tosylate] studied could be grouped as: (1) hydroxybenzylidines; (2) methoxybenzylidines; and (3) nitrobenzylidines substituted at the R position. 2'-Hydroxybenzylidine-HAG, the lead compound, was relatively active in both HT-29 cells and L1210 cells (20 +/- 5 and 13 +/- 4 microM for 50% inhibition of HT-29 and L1210 cell growth respectively). The monohydroxybenzylidene compounds were generally more active than the dihydroxy- and trihydroxybenzylidene-HAG derivatives. The methoxybenzylidene-HAGs were as active as the monohydroxybenzylidene-HAGs. 2'-Hydroxy-4'-methoxybenzylidene-HAG was much more active than 2',4'-dihydroxybenzylidene-HAG. The mononitrobenzylidene-HAGs were more active than the dinitrobenzylidene-HAG compound. In general, L1210 cells were more sensitive to the effects of the HAG compounds than were HT-29 cells. There was good agreement between the concentration of drug required to inhibit the growth of HT-29 cells and that required to inhibit the growth of L1210 cells. There was also good correlation between the ability of HAG derivatives to inhibit ribonucleotide reductase activity and to inhibit tumor cell growth. Some derivatives, such as 2',3',4'- and 3',4',5'-trihydroxybenzylidene-HAG inhibited L1210 cell growth by 50% at lower concentrations (7.8 and 11.9 microM respectively) than the concentrations needed for 50% inhibition of HT-29 cell growth (196 and 234 microM respectively) and ribonucleotide reductase activity (122 and 188 microM respectively). The studies of nucleic acid synthesis in L1210 cells using [3H]cytidine as a precursor showed that 2',3',4'-trihydroxybenzylidine-HAG inhibited DNA synthesis at a lower concentration (29 microM for 50% inhibition) than was needed for the inhibition of RNA synthesis and formation of [3H]deoxycytidine nucleotides in the acid-soluble fraction (320 and 820 microM for 50% inhibition respectively). These results indicate that 2',3',4'-trihydroxybenzylidine-HAG inhibits DNA synthesis in L1210 cells through other mechanisms rather than exclusively through the inhibition of ribonucleotide reductase activity. PMID- 2242015 TI - Dissociation between protein kinase C content and biological responsiveness to phorbol esters in tumor promoter-sensitive (MCF-7) and resistant (RPh-4) cells. AB - A cell line (RPh-4) insensitive to the effects of phorbol esters has been isolated from MCF-7 human breast cancer cells. The growth pattern of RPh-4 cells in the presence of 50 ng/mL (80 nM) 12-O-tetradecanoylphorbol 13-acetate (TPA) is similar to that of parental MCF-7 cells in the absence of TPA. While phorbol esters inhibit MCF-7 cell proliferation and increase cell volume and protein content, no such effects are observed in RPh-4 cells. TPA affects MCF-7 but not RPh-4 cell cycle in two ways: a G1 block and a delayed passage through G2 phase. Profound alterations in protein kinase C content and activity are observed in RPh 4 versus MCF-7 cells, i.e. (i) a dramatic decline in the cellular enzyme content; (ii) a loss of the capacity to translocate upon acute TPA stimulation for the remainder enzyme; and (iii) a lack of stimulation by phorbol esters of the endogenous Mr 28,000 substrate. However, these striking changes are only transient and rapidly reverse when RPh-4 cells are subcultured in TPA-free medium, with a 60% and an almost total recovery, respectively, after 15 days and 3 months. By contrast, a much lower rate of reversion is observed in terms of cell growth responsiveness to TPA with a total insensitivity to phorbol ester after 80 days and a 50% inhibition of RPh-4 cell proliferation after 3.5 months. Our data clearly demonstrate an apparent dissociation between the cellular protein kinase C content and the biological responsiveness to phorbol ester in the variant RPh-4 cells. Moreover, they suggest that the Mr 28,000 protein phosphorylation event is not directly related to the cell growth arrest induced by phorbol esters in MCF-7 cells. PMID- 2242017 TI - An evaluation of the role of glutathione and its associated enzymes in the expression of differential sensitivities to antitumour agents shown by a range of human tumour cell lines. AB - Glutathione and its associated enzyme activities have been quantitated in a series of human tumour continuous cell lines expressing a range of in vitro sensitivities to certain antitumour agents. Fourteen different parental lines and 15 various drug- and X-ray-selected resistant sublines have been studied. Quantitative relationships between total glutathione levels and related enzyme activities and sensitivities to six clinically-useful antitumour drugs or X-rays, as judged by colony forming assays, have been determined by linear regression analysis. A positive correlation has been identified between glutathione levels and sensitivities to cisplatin. Adriamycin, or to X-rays. In addition, positive correlations were noted between cisplatin sensitivities and glutathione peroxidase and reductase activities and for Adriamycin responses with respect to glutathione peroxidase activity, using cumene hydroperoxide as substrate. However, no positive correlations were noted for glutathione levels or these enzyme activities with differential methotrexate, etoposide, vincristine or 5 fluorouracil cytotoxicities. Furthermore, no direct relationship was apparent between total glutathione S-transferase activities and any of these drug or X-ray sensitivities in this series of cell lines. These data appear to provide further evidence linking altered glutathione metabolism with differential cytotoxicities of certain clinically-useful antitumour agents. PMID- 2242016 TI - Blood-glucose-lowering activity of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677). AB - A single oral or intraperitoneal application of 2-(3-phenylpropoxyimido)-butyrate (BM 13.677) resulted in a dose-dependent blood-glucose-lowering effect in fasted guinea-pigs. The threshold dose and the EC50 were estimated as 25 mg/kg and 63 mg/kg, respectively, which is between that of the biguanides phenformin and metformin. A rise in blood lactate concentrations was observed only at high doses of BM 13.677, but was not related to an irreversible metabolic inhibition. Among several rodent species studied the potency of the drug decreased in the order guinea-pig much greater than mouse greater than rat = rabbit. Inhibition of hepatic gluconeogenesis by the drug was demonstrated in the perfused liver or hepatocytes of guinea-pigs. Inhibition of glucose production by the perfused liver in the presence of 0.1 mM BM 13.677 was dependent on the substrate and decreased in the order: lactate greater than pyruvate greater than alanine much greater than propionate greater than glycerol = fructose. This suggests a specific interaction of the drug with a mitochondrial key reaction of gluconeogenesis. Stimulation of glucose oxidation in rat diaphragm by the compound (EC50 = 0.85 mM) suggests that besides inhibition of gluconeogenesis also extrahepatic effects contribute to the blood-glucose-lowering effects of the drug. PMID- 2242018 TI - Vasodilator effects of sarafotoxins and endothelin-1 in spontaneously hypertensive rats and rat isolated perfused mesentery. AB - Sarafotoxins (SRTa, SRTb and SRTc) and ET-1 produced a potent vasodilator effect in spontaneously hypertensive rats in vivo and in rat isolated perfused mesenteries in vitro. Among these peptides SRTc demonstrated the most potent vasodilator activity, and was three times more active than SRTa in both preparations. These peptides induced endothelium-dependent vasodilatation in vitro and pretreatment with methylene blue inhibited this effect, while exposure to the antagonists of other vasodilators did not. In contrast, [nitrophenylsulfenylated Trp21]SRTc, SRTc(1-18) and reduced and S carboxymethylated SRTc caused no vasodilatation in either animal model; the vasodilator effect of acetylated SRTc was less potent than that of SRTc. These results suggest that (i) the vasodilatations of these peptides may be exerted through the release of endothelium derived relaxing factor; (ii) the C-terminal Trp21 and disulfide bonds are essential; and (iii) the N-terminal amino group plays an important role in vasodilator activity. PMID- 2242019 TI - Structure-activity studies with chiral isomers and with segments of the antimitotic marine peptide dolastatin 10. AB - Eighteen configurational isomers of the antimitotic peptide dolastatin 10 (Bai et al., Biochem Pharmacol 39: 1941-1949, 1990) derived from Dolabella auricularia, together with segments obtained as precursors in its synthesis (Pettit et al., J Am Chem Soc 111: 5463-5465, 1989), were examined as inhibitors of tubulin polymerization and as inhibitors of growth of L1210 murine leukemia cells in culture. Dolastatin 10 consists of four amino acids (in order from the amino terminus: dolavaline, valine, dolaisoleucine, and dolaproine), three unique to D. auricularia, linked to an unusual primary amine (dolaphenine, probably derived from phenylalanine) at what would otherwise be its carboxyl terminus. Dolastatin 10 has nine asymmetric carbon atoms, and available isomers included alternate configurations at five positions (positions 9 and 10 in the dolaproine moiety and positions 18, 19 and 19a in the dolaisoleucine moiety). For tubulin polymerization, only alterations at positions 18 and 19 resulted in loss of inhibitory activity of the isomer. In addition, a tripeptide containing dolavaline, valine and dolaisoleucine with all asymmetric carbons identical configurationally to those in dolastatin 10 was found to be about 30% as effective as dolastatin 10 in inhibiting tubulin polymerization. Cytotoxic effects were much more sensitive to alterations in the dolastatin 10 structure. The only modification which did not lead to reduced cytotoxicity was reversal of configuration at position 19a in the dolaisoleucine moiety. Both this isomer and dolastatin 10 had IC50 values of less than 1 nM. Several other isomers had IC50 values with the L1210 cells in the range of 30-90 nM, but these did not correlate well with their inhibitory effects on tubulin polymerization. The tripeptide effective as an inhibitor of tubulin polymerization had no activity against the L1210 cells. PMID- 2242020 TI - Effects of oxygen deficiency and calcium omission on carbon tetrachloride hepatotoxicity in isolated perfused livers from phenobarbital-pretreated rats. AB - The effect of oxygen concentration and Ca2+ omission on CCl4-induced hepatotoxicity was studied in a non-recirculating and hemoglobin-free liver perfusion system using phenobarbital-pretreated rats. With 95% O2-saturated perfusate, infusion of 0.5 mM CCl4 caused an instantaneous increase of thiobarbituric acid reactive substances (TBA-RS) in the effluent perfusate, accompanied by only a slight leakage of K+ and lactate dehydrogenase (LDH). CBrCl3 produced a far greater increase in the TBA-RS level, but again with slight K+ and LDH leakage. With 20% O2-saturated perfusate, CCl4 caused a marked LDH leakage, which was preceded by an early and considerable increase in K+ leakage coupled with Na+ uptake, Ca2+ uptake was initially slight, being enhanced concurrently with the LDH leakage. The TBA-RS level changed biphasically with an initial moderate and a succeeding greater increase coupled with LDH leakage. N,N" Diphenyl-p-phenylenediamine and promethazine suppressed the TBA-RS production, but improved neither K+ nor LDH leakage. Omission of the Ca2+ from the perfusate reduced the initial K+ leakage as well as the later TBA-RS release, and markedly delayed the LDH leakage. In retrograde perfusion under low oxygen supply with Ca2+, CCl4 produced essentially the same toxic manifestations as those observed in the anterograde perfusion. Hepatocytes of the periportal and pericentral areas were not stained with trypan blue in the antero- and retrograde perfusion systems respectively. Thus, oxygen deficiency, rather than lipid peroxidation by itself, and the essential role of extracellular Ca2+ may be important for CCl4-induced hepatic cell necrosis, in which plasma membrane permeability change may be an early and critical event. PMID- 2242021 TI - Lipid peroxidation and protein thiol depletion are not involved in the cytotoxicity of N-hydroxy-2-acetylaminofluorene in isolated rat hepatocytes. AB - Freshly isolated rat hepatocytes were used to study the mechanism of cell death induced by N-hydroxy-2-acetylaminofluorene (N-OH-AAF). Exposure to 1.0 mM N-OH AAF resulted in more than 90% cell death (as measured by LDH leakage) of hepatocytes isolated from male rats within 6 hr. Only 36% of the hepatocytes isolated from female rats died within this period. When inorganic sulfate was omitted from the incubation medium, a 6 hr exposure to 1.0 mM N-OH-AAF resulted in only 40% cell death of male hepatocytes. These findings are in accordance with the sex difference and sulfation dependence of N-OH-AAF hepatotoxicity observed in the rat in vivo. N-OH-AAF decreased glutathione (GSH) in male hepatocytes in a concentration-dependent manner. This GSH consumption was only partly dependent on the presence of inorganic sulfate. No lipid peroxidation was observed during N-OH AAF exposure; N-OH-AAF even prevented endogenous and diethyl maleate (DEM) induced lipid peroxidation. No reduction of free protein thiol groups was found after exposure to N-OH-AAF, even after 75% cell death had occurred. A reduction of protein thiols after N-OH-AAF exposure was observed in GSH depleted hepatocytes (obtained by DEM plus vitamin E pretreatment). Under these conditions N-OH-AAF-induced cell death occurred earlier. Therefore, GSH protects against protein thiol depletion by N-OH-AAF in control cells. N-OH-AAF-induced cell death was preceded by a loss of intracellular ATP. It is concluded, therefore, that neither lipid peroxidation nor depletion of protein thiols, but possibly loss of intracellular ATP, is involved in the sulfation-dependent cytotoxic mechanism of N-OH-AAF in isolated rat hepatocytes. PMID- 2242022 TI - Spermine toxicity and glutathione depletion in BHK-21/C13 cells. AB - Spermine, a polycationic amine, produced a dose-dependent inhibition of BHK 21/C13 cell growth. This response was not due to the extracellular metabolism of spermine by an amine oxidase found in bovine serum, as the toxicity was observed when the cells were grown in medium supplemented with horse serum. Three indices were used to monitor cell growth, cell number, protein content and [3H]thymidine incorporation into DNA. Spermine (2mM) caused significant reductions in all three measurements after a 6-8 hr exposure. The amine was rapidly taken up into the cells reaching levels 15-16-fold greater than in control cells within 2 hr. There was a rapid loss of intracellular reduced glutathione following exposure to toxic concentrations of spermine, which occurred before any effect on cell growth. Three methods for the determination of intracellular glutathione content were compared in this system. The effect on both cell growth and glutathione was reversible following removal of spermine from the extracellular medium. The possible mechanisms involved in this toxic response are discussed with particular reference to the depletion in intracellular reduced glutathione. PMID- 2242023 TI - Multiple molecular forms and lectin interactions of organophosphate-sensitive plasma and liver esterases during development of the chick. AB - Liver and plasma acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase activities of the chick embryo and adult chickens were separated by sucrose density gradient sedimentation and further differentiated by their lectin affinities and organophosphate sensitivities. Changes in plasma cholinesterases during development indicated a characteristic shift in tetrameric (G4) isoforms from a slightly larger G4 AChE in the embryo to G4 BChE in the adult. These changes were not reflected in isoform patterns of liver homogenates, however. Interestingly, the time course of an increase in plasma BChE activity corresponded to the time course of a decrease in liver BChE activity, as if this enzyme was being mobilized and released. The distribution of liver esterases included both monomeric (G1) and G4 BChE and a large p-nitrophenylacetate (p-NPA) esterase activity that was separated into two main peaks by density gradient ultracentrifugation. The effects of organophosphate inhibitors indicated that the two liver p-NPA esterase activities may be regarded as carboxylesterases; however, these enzymes showed very different sensitivities to paraoxon and diisopropylfluorophosphate (DFP), with IC50 values differing by 3 and 4 orders of magnitude. Lectin affinity studies with multiple esterase forms suggested a heterogeneous group of glycoproteins that were packaged at different sites in the liver cell and were consistent with the presence of an intracellular precursor form to plasma BChE. PMID- 2242025 TI - Characterization of repair inhibition by methotrexate of ethylmethanesulfonate and ultraviolet irradiation-induced DNA damage in Chinese hamster cells. PMID- 2242024 TI - Irreversible binding of heme to microsomal protein during inactivation of cytochrome P450 by 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6 trimethylpyridine. AB - The porphyrinogenicity of 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro 2,4,6-trimethylpyridine (DDC) is related to the process of mechanism-based destruction of cytochrome P450 (P450) heme, accompanied by conversion of heme to N-alkylprotoporphyrins (N-alkylPPs). Certain DDC analogues (4-isopropyl, 4 isobutyl, 4-hexyl) are weakly porphyrinogenic in comparison to the potent porphyrinogen, 4-ethyl DDC. We have examined the abilities of these DDC analogues to promote irreversible binding of radiolabeled heme to protein in rat liver microsomal preparations. The goals of this study were to determine whether DDC analogues with different porphyrinogenicities differ in the extents to which they cause heme adduct formation, and whether P450 isozymes differ in their capacities to catalyze heme covalent binding. Incubation of microsomes with NADPH alone promoted heme covalent binding, while loss of spectral P450 heme was minimal or absent. In microsomal incubations containing NADPH, the 4-ethyl, 4-isopropyl, and 4-isobutyl analogues caused heme covalent binding to extents which paralleled their P450 destructive activities. In contrast, 4-hexyl DDC caused less heme covalent binding as a function of P450 loss than the other analogues in microsomes from untreated and beta-naphthoflavone (beta NF)-treated rats. Thus, the weakly porphyrinogenic DDC analogues do not cause greater heme covalent binding than 4-ethyl DDC. Weak porphyrinogenicity, therefore, cannot be explained by diversion of the heme moiety of P450 from conversion to N-alkylPPs towards utilization for formation of heme-derived protein adducts. Treatment of rats with P450 inducing agents altered the degree to which DDC analogues caused heme covalent binding. The greatest heme adduct formation occurred in microsomes from untreated and dexamethasone (DEX)-treated rats, whereas treatment with phenobarbital and especially beta NF reduced heme covalent binding as a function of P450 loss. Thus, these microsomal studies suggest that constitutive P450 isozymes and members of the DEX-inducible P450IIIA subfamily appear to catalyze heme covalent binding, while beta NF-inducible forms such as P450IA1 (P450c) seem to be relatively inactive in this regard. PMID- 2242026 TI - Inositol 1,3,4,5-tetrakisphosphate and regulation of intracellular calcium. PMID- 2242027 TI - Receptor-mediated endocytosis of macromolecular conjugates in selective drug delivery. PMID- 2242028 TI - Phenothiazines inhibit copper and endothelial cell-induced peroxidation of low density lipoprotein. A comparative study with probucol, butylated hydroxytoluene and vitamin E. AB - The effect of two phenothiazines, chlorpromazine (CPZ) and trifluoperazine (TFP) on the copper and endothelial cell-induced peroxidation of low density lipoprotein (LDL) has been studied and compared to that of drugs previously shown to protect LDL against peroxidation: probucol (PBC) and butylated hydroxytoluene (BHT). Incubation with CPZ or TFP inhibited in a dose-dependent manner LDL peroxidation induced either by copper ions or by cultured endothelial cells. Both the electrophoretic mobility and the thiobarbituric reactive substance content of LDL returned to almost normal values in the presence of 50 microM CPZ or TFP. The two studied phenothiazines also strongly inhibited the hydrolysis of LDL phosphatidylcholine which accompanies copper or endothelial cell-induced peroxidation of the particle. CPZ and TFP were as effective as PBC and BHT in inhibiting the LDL peroxidation. Whereas copper or endothelial cell-oxidized LDL were recognized and rapidly catabolized by mouse peritoneal macrophages, CPZ- or TFP-, as well as PBC- or BHT-treated LDL were not. Moreover, it was found that, in contrast to vitamin E, neither CPZ nor PBC reacted with model peroxy radicals formed by gamma irradiation of aerated ethanol. The possible mechanisms underlying this protective effect of phenothiazines against LDL oxidative modification are discussed. PMID- 2242029 TI - Effects of ethanol and inhibitors on the binding and metabolism of acetaminophen and N-acetyl-p-benzoquinone imine by hepatic microsomes from control and ethanol treated rats. AB - Acetaminophen is metabolized by cytochrome P450 to N-acetyl-p-benzoquinone imine (NABQI). This metabolite reacts with critical cellular macromolecules to give toxicity. The administration of 10% ethanol in the drinking water to 100 g male rats for 6 weeks markedly increases the toxicity of acetaminophen. This increase was associated with a 71% increase in microsomal protein binding of acetaminophen [4.8 pmol/min/mg protein in control microsomes versus 8.2 pmol/min/mg protein in ethanol microsomes (P less than 0.01)] and a 131% increase in aniline hydroxylase [0.52 nmol/min/mg protein in control microsomes versus 1.20 nmol/min/mg protein in ethanol microsomes (P less than 0.001)]. On the other hand, cysteine conjugation of acetaminophen showed an increase of only 12% [2.8 nmol/min/mg protein in control microsomes versus 3.1 nmol/min/mg protein in ethanol microsomes (P less than 0.05)]. Ethylmorphine- and benzphetamine N-demethylases did not increase. In microsomes from both control and ethanol animals, imidazole (1 mM) inhibited the two N-demethylases, aniline hydroxylation and acetaminophen binding by 85-95% but inhibited the cysteine conjugation by only 50%. For control and ethanol animals, both 80% CO/20% O2 and SKF-525A (1 mM) totally inhibited cysteine conjugation but only inhibited the other activities by about 36-60%. KCN (1 mM) had no effect on any of the activities except protein binding (60-67% inhibition). Scavengers of reactive oxygen [mannitol (1 mM), dimethyl sulfoxide (1 mM), superoxide dismutase (15 micrograms/mL) and catalase (65 micrograms/mL)] had no effect on any of the reactions. Of all these treatments only CO/O2 decreased the protein binding and cysteine conjugation of NABQI in the presence of either NADP+ or NADPH. The data from the inhibitor studies and the effect of ethanol on acetaminophen and NABQI metabolism would suggest that protein binding and cysteine conjugation are catalyzed by different isozymes of cytochrome P450. Finally, the current results indicate that the increased toxicity of acetaminophen observed with ethanol more closely parallels the increase in protein binding activity rather than cysteine conjugation. PMID- 2242030 TI - Effect of 3- and 4-thia-substituted fatty acids on glycerolipid metabolism and mitochondrial beta-oxidation in rat liver. AB - Treatment of normolipidemic rats by alkylthiopropionic acid (CETTD), resulted in a dose- and time-dependent increase in total dihydroxyacetone phosphate acyltransferase (DHAPAT) activity, in extent comparable to that of 3 thiadicarboxylic acid (BCMTD) and alkylthioacetic acid (CMTTD). Thus, in CETTD- and CMTTD-treated rats, the specific DHAPAT activity increased in the microsomal, peroxisomal and mitochondrial fractions. In contrast, repeated administration of the peroxisome proliferator, BCMTD, decreased the specific DHAPAT activity both in the peroxisomal fraction and in purified peroxisomes. A three-fold increase in specific activity was, however, revealed in the mitochondrial fraction. Whether the variation of the DHAPAT activity in the mitochondrial and microsomal fractions among the feeding groups can be explained by increased number of enlarged and small peroxisomes sedimenting in the fractions, are to be considered. Subcellular fractionation studies confirmed previous findings that rat liver glycerophosphate acyltransferase (GPAT) was located both in mitochondria and the microsomal fraction. BCMTD was considerably more potent than CMTTD in stimulating the microsomal and mitochondrial GPAT activities. Administration of CETTD marginally affected the isoenzymes of GPAT. Diacylglycerol acyltransferase (DGAT) activity was increased by 35% in BCMTD and CMTTD treated rats, but by administration of CETTD the enzyme activity was decreased by more than 80%. The acyl-CoA cholesterol acyltransferase (ACAT) activity was marginally affected in animals treated with BCMTD, CMTTD and CETTD. Thus, the results indicate that the initial steps in the synthesis of triacylglycerols and ether glycerolipids as well as the last step in triacylglycerol synthesis could not be identified as mediating the fat accumulation or the lowering of triacylglycerol content in liver of CETTD, or BCMTD and CMTTD treated rats. On the other hand, CMTTD increased the palmitoyl CoA oxidation in mitochondria, and CETTD considerably inhibited the activity. Therefore, it is conceivable that the development of fatty liver with CETTD is mostly due to inhibition of mitochondrial beta-oxidation. PMID- 2242031 TI - Electron transport and protection of liver slices in the late stage of paracetamol injury. AB - Cell injury by chemicals takes place in two stages, initial chemical interaction between the material and cell components, and subsequent stages of adaptation or failure of response to chemical modification of some parts of the cell apparatus. Paracetamol toxicity was studied in an in vitro system using liver slices incubated in two stages. During the first 2 hr slices were exposed to 10 mM paracetamol and this was absent during the following 4 hr of incubation. Damage was quantified at the end by measuring leakage of lactate dehydrogenase (LDH), increase in water content and potassium loss. Treatment of slices with 10 microM DCPIP or 2 mM ethanol in the second period of incubation prevented paracetamol induced damage. The protective effect was not dependent on the activity of P450 since the second stage of incubation was insensitive to SKF-525A. The protective effect of ethanol was blocked by the presence of 1 mM pyrazole suggesting that ethanol needs to be metabolized to exert its effect. The addition of 20 mM pyruvate reversed the protection provided by ethanol. Nicotinamide did not alter toxicity or protection by ethanol. These findings suggest an increase of NADH and NADH/NAD ratio as the most probable explanation for the protective effect observed. The role of reducing equivalents in detoxification of quinones such as NAPQI by formation of hydroquinones, is discussed in relation to the mechanism of cell injury by paracetamol. PMID- 2242032 TI - Effects of novel bile salts on cholesterol metabolism in rats and guinea-pigs. AB - Novel bile salts (quaternary ammonium conjugates) inhibited cholic acid binding and transport in everted ileal sacs in vitro. The cationic piperazine conjugate of lithocholic acid (di-iodide salt, compound 8, BRL 39924A) appeared most active, inhibiting binding by 29% and transport by 59% in guinea-pig ileum (200 microM). BRL 39924A also inhibited taurocholate uptake into guinea-pig ileal sacs and cholate uptake into rat ileal sacs and was selected for further study in vivo. In hyperlipidaemic rats, BRL 39924A significantly raised cholesterol 7 alpha-hydroxylase activity and decreased hepatic accumulation of exogenous cholic acid. HDL cholesterol concentration in the serum increased and the level of VLDL plus LDL cholesterol decreased. In hyperlipidaemic guinea-pigs. BRL 39924A lowered serum total cholesterol and triglyceride levels. Although metabolic changes were less than those achieved with the bile acid sequestrant, cholestyramine, the doses of BRL 39924A used were much lower (100-500 mg/kg body wt). Selective inhibition of receptor mediated bile acid uptake may be associated with local side-effects but these novel bile salts are useful pharmacological tools to examine the effects of receptor blockade on lipoprotein metabolism. PMID- 2242033 TI - Stimulation of human polymorphonuclear leukocytes potentiates the uptake of diclofenac and the inhibition of chemotaxis. AB - Diclofenac sodium, a non-steroidal anti-inflammatory drug, has been shown to impair the stimulation of human polymorphonuclear leukocytes (PMNs) by chemoattractants. To gain insight into the mechanism of action of this agent, we investigated the uptake of diclofenac by resting and activated PMNs and the effect of the drug on PMN locomotion. During incubation of resting PMNs at 37 degrees in the presence of 78 microM (25 micrograms/mL) diclofenac, drug uptake reached a plateau in less than 2 min. The resulting cellular to extracellular diclofenac concentration ratio (C/E) was 1.01 +/- 0.13 (mean +/- SD). Stimulation of PMNs at 37 degrees but not at 4 degrees with the chemoattractant formyl methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), induced a rise in diclofenac uptake, which was dependent on incubation time and diclofenac and stimulus concentrations. Maximal C/E was 1.83 +/- 0.18 and 4.40 +/ 0.60 (mean +/- SD) for PMNs stimulated with 10 microM fMLP and 0.16 microM PMA, respectively. The diclofenac associated with PMNs was predominantly present in the soluble fraction of disrupted cells. Interestingly, PMNs which were pretreated with diclofenac and stimulated with fMLP, exhibited impaired random and directional locomotion induced by activated serum, as compared to controls, i.e. PMNs treated with diclofenac alone or fMLP alone. Thus, stimulation of PMNs enhances diclofenac uptake and potentiates the drug impairment of chemotactic activity. These findings could explain, in part, the observed anti-inflammatory properties of this compound. PMID- 2242034 TI - Purification and characterization of 3-mercaptopyruvic acid S-conjugate reductases. AB - Three kinds of 3-mercaptopyruvic acid S-conjugate reductase (MPR-I, MPR-II and MPR-III) were purified from rat liver cytosol. These enzymes reduced 3 mercaptopyruvic acid S-conjugates derived from cysteine conjugates and some endogenous alpha-keto acids to the corresponding alpha-hydroxy acids in the presence of either NADH (for MPR-I and MPR-II) or NADPH (MPR-III), while simple aldehydes or ketones did not significantly induce substrate activity. The molecular weight of the present enzymes was about 80 kDa composed of two subunits of the same molecular weight. Km values of MPR-I, MPR-II and MPR-III were 0.38, 0.06 and 0.29 mM for S-(4-bromophenyl)-3-thiopyruvic acid, respectively, and 0.15 mM for NADH (MPR-I, MPR-II) and NADPH (MPR-III). Vmax values of MPR-I, MPR-II and MPR-III for this substrate were 5.3, 20 and 13 nmol/min/mg, respectively. The sulphydryl-modifying agents inhibited the enzyme activities of all the three reductases. Based on the properties including substrate selectivity for alpha keto acids derived from aromatic amino acids, we assumed that MPR-II and aromatic alpha-keto acid reductase are the same enzyme, while enzymes similar to MPR-I and MPR-III have not been reported. From the viewpoints of metabolism of xenobiotics, these enzymes are likely to be important in biotransformation of cysteine conjugates to 3-mercaptolactic acid S-conjugates. PMID- 2242035 TI - Warfarin resistance in a Chicago strain of rats. AB - A warfarin-resistant strain of rats trapped in Chicago was studied to determine the mechanism of the warfarin resistance. The Chicago-resistant rats (CR) differ from a Welsh-resistant strain (WR) which has a vitamin K epoxide reductase that is insensitive to warfarin. The epoxide and dithiol-dependent quinone reductases of the CR rats were as sensitive to warfarin as the normal enzyme. Unlike the irreversible warfarin inhibition seen in normal rats, the warfarin inhibition of the epoxide reductase from the CR strain was partially reversible in vitro. In this respect, the CR rats appeared similar to a Scottish warfarin-resistant strain. The same steady-state level of warfarin (40 ng/mg protein) in liver microsomes could be achieved in normal and CR strain rats following a few days ingestion of a diet containing 50 ppm warfarin, but clearance of warfarin (1 mg/kg) from the liver microsomes was more rapid in the CR strain than in normal rats, and the recovery of epoxide reductase activity and prothrombin levels was more rapid. The mechanism of warfarin resistance in the CR strain differed from the warfarin resistance mechanisms of both the Scottish- and Welsh-resistant rat strains. The combination of an increased rate of warfarin clearance and the partially reversible inhibition of the epoxide reductase would be sufficient to allow the rats to survive a limited exposure to warfarin. PMID- 2242036 TI - Purification and characterization of the human ovarian LH/hCG receptor and comparison of the properties of mammalian LH/hCG receptors. AB - Methods previously published by us [Wimalasena et al., J Biol Chem 260: 10689 10697, 1985; Wimalasena et al., J Biol Chem 261: 9416-9420, 1986] were utilized to solubilize the human corpus luteal leuteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor with 3-[(3-cholamide-propyl)dimethylammonio]-1 propanesulfonate (CHAPS) and to purify the receptor by two steps of hCG-Sepharose affinity chromatography. The specific binding capacity (SBC) of the purified human receptor was 7510 pmol/mg protein, and KA = 2.2 x 10(9) M-1 when iodo hCG was competed by hCG; the yield was 4-7% of starting activity. When hLH was used in competition with hCG, specific binding capacity was 7900 pmol/mg protein and KA 1.0 x 10(9) M-1. Silver staining and autoradiography demonstrated a single protein of Mr 78,000 under reducing and Mr 58-62 x 10(3) under nonreducing conditions. Rat ovarian LH/hCG receptor was purified by similar methods and the KA of 3.5 x 10(10) M-1 for hCG was substantially different from the KA for hLH which was 2.1 x 10(9) M-1. Mr of the rat protein was 78-82 x 10(3) (reduced) and 58-62 x 10(3) (nonreduced) when analyzed by silver staining and autoradiography. For the first time, human LH/hCG receptor has been purified to apparent homogeneity, and its Mr of 78,000 was essentially identical to the Mr values of purified rat and porcine receptors. PMID- 2242037 TI - [3H]mecamylamine binding to rat brain membranes. Studies with mecamylamine and nicotine analogues. AB - Mecamylamine, an antagonist to nicotine, does not compete at the nicotinic recognition site, but is believed to block the ion channel of the nicotinic receptor. The present study demonstrates specific, saturable [3H]mecamylamine binding in rat brain membranes. [3H]Mecamylamine binding was destroyed by heating at 100 degrees and trypsin. Scatchard analysis revealed the presence of two sites with Kd values of 9.6 x 10(-8) and 1.1 x 10(-6) M and Bmax values of 7 x 10(-12) and 3 x 10(-11) mol/mg protein respectively. A good correlation was observed between the Ki values for [3H]mecamylamine binding of a number of mecamylamine and related analogues and their ability to block nicotine-induced prostration in rats and seizures in mice. Inorganic cations, particularly divalent, and various ion channel blockers, such as phencyclidine and verapamil, exhibited a high affinity for the [3H]mecamylamine site. Although mecamylamine did not block nicotine binding, nicotine and its analogues exhibited a high affinity for the [3H]mecamylamine site, a finding which suggests that nicotine acts directly on ion channels as well as the nicotinic cholinergic recognition sites. The data are consistent with the notion that mecamylamine interacts with the open ion channel of the nicotinic receptor. PMID- 2242038 TI - Anti-oxidative profile of lobenzarit disodium (CCA). AB - The effects of lobenzarit disodium (CCA) on various species of activated oxygen were investigated in chemiluminescence experiments. CCA showed a quenching effect against hydroxyl radicals generated by Fenton reaction. The inhibition of CCA was much more intense than that of mefenamic acid which is an anti-inflammatory drug and an analogous compound to CCA. CCA also showed a quenching effect against singlet oxygen generated in enzymatic systems. However, CCA had no effect against superoxide anion radicals generated in the xanthine oxidase-hypoxanthine system. As a model of lipid peroxidation and protein alteration induced by activated oxygen, we examined the auto-oxidation of linolenic acid and the UV irradiation of immunoglobulin G (IgG). CCA inhibited the production of lipid peroxide; however CCA did not show a direct quenching action against lipid radicals which had been previously generated. CCA also inhibited the IgG alteration induced by UV irradiation. These results indicate that CCA has anti-oxidative actions with specificity for activated oxygen species and that CCA protects against lipid and protein damage induced by activated oxygen. PMID- 2242040 TI - Inhibition of protein kinase C by the tyrosine kinase inhibitor erbstatin. AB - We examined the tyrosine kinase inhibitor erbstatin and several derivatives for their ability to inhibit serine/threonine protein kinases in vitro. Erbstatin was found to inhibit protein kinase C (PKC) with an IC50 of 19.8 +/- 3.2 microM. A trihydroxy derivative of erbstatin inhibited PKC with similar potency, whereas the corresponding methoxy derivatives were inactive. Inhibition by erbstatin was competitive with ATP (Ki = 11.0 +/- 2.3 microM) and non-competitive with the phosphate acceptor, either histone or the synthetic peptide kemptide. Action of erbstatin at the catalytic site of PKC was further indicated by the findings that it inhibited the catalytic fragment of PKC but did not inhibit the interaction of phorbol ester with the intact enzyme. Erbstatin had a similar potency against three PKC isozymes (alpha, beta, and gamma) examined. In addition, erbstatin was found to inhibit other serine/threonine kinases (assayed at their Km for ATP). The greatest potency was observed versus the cyclic nucleotide-dependent kinases, while lower potency was seen versus myosin light chain kinase. These observations are discussed in terms of the structure and kinetic properties of PKC and the epidermal growth factor receptor tyrosine kinase. PMID- 2242039 TI - Mechanism of the microsomal demethylation of 1-aryl-3,3-dimethyltriazenes. AB - The metabolism of 1-aryl-3,3-dimethyltriazenes by phenobarbital-induced rat liver microsomes results in the formation of 1-aryl-3-methyltriazenes and formaldehyde. Intermolecular kinetic deuterium isotope effects for the reaction are found to be 1.0 (+/- 0.03) in both Vmax and Vmax/Km, respectively. The intramolecular kinetic deuterium isotope effects in Vmax and Vmax/Km are found to be 4.8 (+/- 0.05). There is no correlation of Vmax or Vmax/Km with calculated ionization potentials of the triazenes. For 3-ethyl-3-methyltriazene comparison of values of Vmax and Vmax/Km for ethyl vs methyl loss give rise to values of 3.68 in Vmax and 2.02 in Vmax/Km. Thus, loss of an ethyl group is favoured. The results are discussed in terms of a mechanism in which the triazene undergoes direct hydrogen atom abstraction to form a carbon centred radical. This radical subsequently forms a hydroxymethyltriazene that collapses to formaldehyde and a monomethyltriazene. PMID- 2242041 TI - Short term treatment by fenofibrate enhances oxidative activities towards long chain fatty acids in the liver of lean Zucker rats. AB - Lean Zucker rats were dosed orally for 1 week with fenofibrate (100 mg/kg/day). Liver weights of treated rats, expressed as per cent of body weight, were increased, while protein, DNA and triacylglycerol contents were not changed to any great extent per gram of liver, but increased when expressed per whole liver. Compared with the control animals, activities of fatty acid oxidase, of the peroxisomal fatty acid-oxidizing system and of catalase were markedly enhanced by fenofibrate, both per gram of liver and per total liver, while urate oxidase activity was slightly depressed when expressed per gram of liver. The activity of cytochrome c oxidase used as a mitochondrial marker was only higher when expressed per total liver. Besides, fenofibrate treatment induced a pronounced increase in the mitochondrial activities of carnitine palmitoyl- and acetyltransferases, of palmitoyl-CoA dehydrogenase and of carnitine-dependent oleate oxidation. Fenofibrate also enhanced significantly the carnitine content in liver and hepatic mitochondria. Malonyl-CoA content per gram of liver was found to be twice as high as in control rats, while the sensitivity of carnitine acyltransferase I to malonyl-CoA inhibition was hardly altered. The drug enhanced the percentage of palmitic acid in lipids of liver, but not in adipose tissues. The present data show that fenofibrate induced greater oxidative activities towards fatty acids, even in the lean animal. This stimulation could be related to the energy used for building new cells. In turn, at the same time of treatment, an enhanced fatty acid synthesis would provide specific fatty acids for the formation of new membranes. This latter effect will eventually disappear and the maintenance of a higher fatty acid oxidation may explain part of the overall hypolipaemic effect of fenofibrate. PMID- 2242042 TI - Distribution of cytochrome P450 activities towards alkoxyresorufin derivatives in rat brain regions, subcellular fractions and isolated cerebral microvessels. AB - The regional and subcellular distributions of rat brain cytochrome P450 and cytochrome P450-dependent activities were examined. Cytochrome P450 was found to be mainly localized in mitochondria in all the six cerebral regions studied. The activities of the isoforms mostly implicated in drug metabolism, cytochromes P450 b and c, were measured by the dealkylation of two alkoxyresorufins, that are sensitive probe substrates for these isoforms. These activities have been measured in microsomal and mitochondrial fractions obtained from six different regions in male rat brains, as well as in microvessels. Resorufin derivatives dealkylation specific activities were higher in brain microsomal fractions than in hepatic ones in all the six regions examined when results were expressed per cytochrome P450 content. These brain microsomal specific activities were also higher than in mitochondrial fractions. Olfactory bulbs showed the highest cytochrome P450 content and activities in both microsomal and mitochondrial fractions. A sex-linked difference in cytochrome P450-dependent activities was also found. After an in vivo inducing pretreatment of rats, only 3 methylcholanthrene induced ethoxyresorufin O-deethylase activity, in the three preparations studied. These results provided (i) direct evidence that cytochromes P450 b and c isoforms are active in brain microsomal fractions, with regional and sex-linked differences, and (ii) the first demonstration of cytochrome P450 dependent activities in isolated rat brain microvessels. PMID- 2242043 TI - In vitro effects of eight-carbon fatty acids on oxidations in rat liver mitochondria. AB - Sodium valproate, a commonly used anticonvulsant agent, is a simple branched chain fatty acid which interferes with beta-oxidation and ammonia metabolism in most patients, with hepatotoxic consequences in some cases. Rat liver mitochondria incubated with valproate displayed time-dependent inhibitions of state 3 oxidation rates with all the substrates tested, but most markedly with glutamate, pyruvate, alpha-ketoglutarate and acylcarnitines (Ki = 125 microM with glutamate and palmitoylcarnitine, and 24 microM with pyruvate). The inhibition of glutamate appeared to be specifically directed against the glutamate dehydrogenase pathway of this oxidation. Valproate was less effective when added to uncoupled mitochondria, suggesting the formation of an inhibitory species by an ATP-dependent mechanism. Mitochondria from clofibrate-treated rats were less sensitive to valproate inhibition. Neither fasting nor the presence of 1 mM L carnitine affected the inhibition of beta-oxidation. The branched-chain isomer, 2 ethylhexanoic acid, had similar effects to valproate, but the straight-chain octanoic acid was totally different in its spectrum of actions on mitochondria. The data support the theory that valproate may inhibit by sequestration of CoA as valproyl-CoA, but also suggest that there are other mechanisms responsible for some of the inhibitions. Furthermore, it argued that while mitochondrial respiration is decreased, valproate is not an inhibitor of oxidative phosphorylation per se. PMID- 2242044 TI - Morphine-induced effects on hepatic metabolism in the male rat depends on an intact pituitary gland. PMID- 2242045 TI - Cytosolic phenol and steroid sulphotransferase activities are decreased in a sex dependent manner in streptozotocin-induced diabetic rats. PMID- 2242046 TI - Altered operant behavior of adult rats after perinatal exposure to a 60-Hz electromagnetic field. AB - Rats were sham exposed or exposed perinatally to a 60-Hz electromagnetic field, 22 days in utero and the first 8 days post partum. Each of the 30 once-daily exposures was 20 h in duration. The electric component of the field was vertical 30 kV/m rms, and the magnetic field component was 100 microTG rms. Later, as adults, male rats were trained to emit an operant response when reinforced with food on a multiple, random-interval schedule. Exposed rats (N = 21) gradually came to respond at significantly lower rates than did sham-exposed controls (N = 20). This finding was confirmed and extended in a second, independently performed experiment. After a sequence including operant conditioning followed by experimental extinction of responding and then by a suspension of conditioning and finally by more than a month of reconditioning, slower rates of responding were found to persist in the adult animals. The evidence of altered behavior several months after combined, fetal-neonatal exposure to an electromagnetic field presents an interesting contrast with other findings: Field-exposed rats did not differ from sham-exposed rats in terms of body mass, physical appearance, grossly observed activity level, or incidence of disease. PMID- 2242047 TI - Magnetic resonance imaging: calculation of rates of energy absorption by a human torso model. AB - The three-dimensional impedance method was used to estimate specific absorption rate (SAR) in a human-torso model during exposure to the time-varying and static magnetic fields used in magnetic resonance imaging (MRI). Analytical data for discrete tissues as well as the entire torso are presented. Generalized equations were derived that enable calculation of whole-torso SAR over a broad range of conditions. In addition, the impedance method can generate data about internal distributions of SAR, which are needed to predict critical organs that might undergo excessive elevations of temperature. Fair to good agreement was found between impedance-method SAR and those predicted by simple phenomenological models. PMID- 2242048 TI - Dominant lethal studies in male mice after exposure to a 50-Hz electric field. AB - Male C3H/He mice were sham-exposed or exposed continuously for 2 weeks to a vertical, 50-Hz, electric field at 20 kV/m rms. Densities of currents induced in the testes are estimated to be near 100 microA/m2. After the exposure, each male was mated with two different female mice each week during a period of 8 weeks. By this schedule, female mice were impregnated with sperm that had been exposed to the electric field at different stages of the spermatogenic cycle. No significant differences as a function of exposure condition were observed in pregnancy rates or in survival of embryos before or after implantation. The absence of effects was not due to insensitivity of assays; other mice that were exposed to X-rays (dose to testes = 1.5 Gy) presented reliable evidence of mutagenesis. PMID- 2242049 TI - A model to assess personal exposure to ELF magnetic fields from common household sources. AB - Emission data are inadequate to characterize the contribution of a source to the total personal extremely-low-frequency (ELF) magnetic field exposure. In this paper, a simple model is proposed that takes into consideration the position of the subject with respect to the source and the duration of exposure. The magnetic field is spatially averaged over the whole body of the exposed subject and integrated over time. Exposure is regarded as significant if it approaches or exceeds 400 microT-h/year. By use of this method, the ELF magnetic fields generated by several household sources were compared with the levels of residential external sources, to assess their relative significance. Some common domestic electrical appliances are found to be responsible for an exposure comparable to that from power lines. When the model is used to assess exposure to electric blankets, apparently conflicting findings may be reconciled. PMID- 2242050 TI - Proflavin and microwave radiation: absence of a mutagenic interaction. AB - The potential ability of radiofrequency electromagnetic radiation (RFR) in the microwave range to induce mutagenesis, chromosomal aberrations, and sister chromatid exchanges in mammalian cells is being explored in our laboratories. In addition, we have also been examining the ability of simultaneous exposure to RFR and chemical mutagens to alter the genotoxic damage induced by chemical mutagens acting alone. We have performed experiments to determine whether there is an interaction between 2.45-GHz, pulsed-wave, RFR and proflavin, a DNA-intercalating drug. The endpoint studied was forward mutation at the thymidine kinase locus in L5178Y mouse leukemic cells. Any effect on the size distribution of the resulting colonies of mutated cells was also examined. The exposures were performed at net forward powers of 500 or 600 W, resulting in a specific absorption rate (SAR) of approximately 40 W/kg. The culture-medium temperature reached a 3 degrees C maximal increase during the 4-h exposure; appropriate 37 degrees C and convection heating temperature controls (TC) were performed. In no case was there any indication of a statistically significant increase in the induced mutant frequency due to the simultaneous exposure to RFR and proflavin, as compared with the proflavin exposures alone. There was also no indication of any change in the colony-size distribution of the resulting mutant colonies, neither, and there was no evidence in these experiments of any mutagenic action by the RFR exposure alone. PMID- 2242051 TI - Importance of alignment between local DC magnetic field and an oscillating magnetic field in responses of brain tissue in vitro and in vivo. AB - The frequency dependence of the electric and magnetic (EM)-field-induced release of calcium ions from an in vitro brain tissue preparation has been shown to be a function of the density of the local DC magnetic field (Bdc). In this study, we demonstrate that the relative orientation of the Bdc and the magnetic component (Bac) of a 315-Hz EM signal (15 Vrms/m and 61 nTrms) are crucial for the induced release to be observed. The induced release occurs only when the Bdc and the Bac are perpendicular, and not when they are parallel. This finding is consistent with a magnetic resonance-like transduction mechanism for the conversion of EM energy into a physicochemical change, and contrasts with the requirement for parallel Bdc and Bac components in the diatom-mobility experiments of Smith et al. A review of the exposure conditions in the rat behavioral experiments conducted by Thomas et al. identifies unhydrated calcium and zinc ions as alternatives to lithium ions as candidates for interaction under parallel magnetic-field orientations but fails to reject perpendicular orientations as an alternative basis for the phenomenon. Investigators that attempt to confirm the rat behavioral experiments should be aware of the conflicting exposure conditions that can be assumed to be operative, and they should design their experiments to test all conditions accordingly. PMID- 2242052 TI - Development of chicken embryos in a pulsed magnetic field. AB - Six independent experiments of common design were performed in laboratories in Canada, Spain, Sweden, and the United States of America. Fertilized eggs of domestic chickens were incubated as controls or in a pulsed magnetic field (PMF); embryos were then examined for developmental anomalies. Identical equipment in each laboratory consisted of two incubators, each containing a Helmholtz coil and electronic devices to develop, control, and monitor the pulsed field and to monitor temperature, relative humidity, and vibrations. A unipolar, pulsed, magnetic field (500-microseconds pulse duration, 100 pulses per s, 1-microT peak density, and 2-microseconds rise and fall time) was applied to experimental eggs during 48 h of incubation. In each laboratory, ten eggs were simultaneously sham exposed in a control incubator (pulse generator not activated) while the PMF was applied to ten eggs in the other incubator. The procedure was repeated ten times in each laboratory, and incubators were alternately used as a control device or as an active source of the PMF. After a 48-h exposure, the eggs were evaluated for fertility. All embryos were then assayed in the blind for development, morphology, and stage of maturity. In five of six laboratories, more exposed embryos exhibited structural anomalies than did controls, although putatively significant differences were observed in only two laboratories (two-tailed Ps of .03 and less than .001), and the significance of the difference in a third laboratory was only marginal (two-tailed P = .08). When the data from all six laboratories are pooled, the difference in incidence of abnormalities in PMF exposed embryos (approximately 25 percent) and that of controls (approximately 19 percent), although small, is highly significant, as is the interaction between incidence of abnormalities and laboratory site (both Ps less than .001). The factor or factors responsible for the marked variability of inter-laboratory differences are unknown. PMID- 2242053 TI - Electric fields and surface charges induced by ELF magnetic fields. AB - A method is described for evaluating electric fields induced by ELF magnetic fields into electrically inhomogeneous, low-conductivity (less than 5 S/m) structures. It is applied to cylinders and spheres, and numerical results are given for electrical properties that are representative of some tissues, or of cells embedded either in saline solution or a tissue matrix. Surface currents on spherical cell boundaries are estimated and compared with thermal noise due to ion motion. PMID- 2242054 TI - [Cloning, structure and expression of the full-size lon gene in Escherichia coli coding for ATP-dependent La-proteinase]. AB - Assembly of the full Escherichia coli K-12 lon gene from the EcoRI--SphI fragment of the bacterial DNA ("modified" gene) cloned and sequenced earlier and the PstI fragment of the same DNA containing 3'-terminal region of the lon gene has been performed. Both "modified" and full genes showed all phenotype properties of lon gene. The complete nucleotide sequence of the gene (2770 bp) coding for the 784 amino acid sequence of protease La was determined. Location of catalytically active serine, histidine and aspartic acid residues was suggested, and ATP binding site found. The lon gene and protease La structures we found are compared with those described independently and differences observed are discussed. PMID- 2242055 TI - [Automated H-phosphonate synthesis of oligoribonucleotides using 2'-O tetrahydropyranyl protective group]. PMID- 2242056 TI - [The structure of carbohydrate chains of riboflavin-binding glycoprotein from chicken egg protein. III. 1H-NMR spectroscopy (500 MHz) of neutral fucosylated oligosaccharides]. AB - Using LiBH4/ButOH treatment, oligosaccharides were cleaved off the hen egg white riboflavin-binding glycoprotein. HPLC led to the isolation of four fucose containing oligosaccharide alditols, whose structure was elucidated by means of 1H NMR 500 MHz spectroscopy. The main fucosylated oligosaccharide, also present in hen ovomucoid, was found to be a biantennary carbohydrate chain of N acetyllactosamine type. PMID- 2242057 TI - [The use of antibodies against DNA modified by trans-diamminedichloroplatinum for identification of specific DNA sequences]. AB - DNA modified by trans-diamminedichloroplatinum (trans-DDP) is suggested as an effective probe for non-isotopic hybridisation. Highly specific anti trans-DDP DNA antibodies and peroxidase-conjugated antibodies to antirabbit Ig and protein A system have been used for the hybrids visualisation. This method allows one to detect 2 pg/mm2 DNA. PMID- 2242058 TI - The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. AB - Clinical criteria for the classification of symptomatic idiopathic (primary) osteoarthritis (OA) of the hands were developed from data collected in a multicenter study. Patients with OA were compared with a group of patients who had hand symptoms from other causes, such as rheumatoid arthritis and the spondylarthropathies. Variables from the medical history, physical examination, laboratory tests, and radiographs were analyzed. All patients had pain, aching, or stiffness in the hands. Patients were classified as having clinical OA if on examination there was hard tissue enlargement involving at least 2 of 10 selected joints, swelling of fewer than 3 metacarpophalangeal joints, and hard tissue enlargement of at least 2 distal interphalangeal (DIP) joints. If the patient had fewer than 2 enlarged DIP joints, then deformity of at least 1 of the 10 selected joints was necessary in order to classify the symptoms as being due to OA. The 10 selected joints were the second and third DIP, the second and third proximal interphalangeal, and the trapeziometacarpal (base of the thumb) joints of both hands. Criteria derived using the "classification tree" method were 92% sensitive and 98% specific. The "traditional format" classification method required that at least 3 of these 4 criteria be present to classify a patient as having OA of the hand. The latter sensitivity was 94% and the specificity was 87%. Radiography was of less value than clinical examination in the classification of symptomatic OA of the hands. PMID- 2242059 TI - Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis. AB - Levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in patients with rheumatoid arthritis from 5 centers involved in the Arthritis, Rheumatism, and Aging Medical Information System were correlated with the use of specific antirheumatic medications. Elevated levels of SGOT and SGPT were most frequent in patients taking salicylates and methotrexate (MTX) and least frequent in patients taking hydroxychloroquine. The combination of MTX and salicylates greatly increased the frequency of abnormal liver enzyme values. In contrast, the addition of hydroxychloroquine to a regimen of either MTX or aspirin essentially eliminated the SGOT and SGPT abnormalities. Results from all 5 centers were consistent and remained so after adjustment for age, sex, and disease duration. Knowledge of these important drug interactions may permit continuation of MTX therapy in patients in whom the drug might otherwise be discontinued. PMID- 2242060 TI - The post-occlusive hyperemic response in patients with systemic sclerosis. AB - We investigated post-ischemic hyperreactive cutaneous blood flow in patients with primary Raynaud's phenomenon and Raynaud's phenomenon secondary to systemic sclerosis (SSc). Reactive hyperemia was measured over a locally warmed area of skin, using a laser Doppler flowmeter, following 5 minutes of suprasystolic occlusion of blood flow. We found that patients with primary Raynaud's phenomenon had normal post-ischemic blood flow compared with normal controls. In contrast, patients with SSc had reduced levels of baseline and peak blood flow compared with either the primary Raynaud's phenomenon patients or the normal subjects. Infusion of carbaprostacyclin, a potent prostacyclin analog vasodilator, did not increase blood flow in the SSc patients, nor did it restore the reactive hyperemic response. These findings are consistent with the hypothesis that patients with the nonvasoconstricted condition of SSc have fixed structural defects that limit cutaneous microvascular blood flow. PMID- 2242061 TI - Diffusing capacity of the lung and nifedipine in systemic sclerosis. AB - Lung involvement in systemic sclerosis may be due in part to a functional abnormality of the pulmonary vasculature. To investigate the possible role of a pulmonary vasospastic process in this disorder, 21 non-smoking patients who had no evidence of cardiac disease or pulmonary hypertension were evaluated with pulmonary function tests prior to administration of nifedipine, 30 minutes after a single oral dose of nifedipine (20 mg), and after 4 weeks of treatment with nifedipine (10 mg 3 times daily). Treatment with nifedipine did not significantly change any of the pulmonary function values, except for the carbon monoxide diffusing capacity (DLCO). The linear trend between the individual DLCO values at baseline and their changes immediately following the initial 20-mg dose of nifedipine (r = -0.603, P = 0.02) and after 4 weeks of treatment (r = -0.636, P = 0.01) showed that the lower the DLCO value at baseline, the greater the improvement caused by nifedipine. These findings support the hypothesis of a potentially reversible pulmonary vasospasm in systemic sclerosis and suggest that nifedipine may be useful in the treatment of lung disease in these patients; however, further studies are needed. PMID- 2242062 TI - A subluxing arthropathy associated with the anti-Jo-1 antibody in polymyositis/dermatomyositis. AB - Of 180 patients with polymyositis/dermatomyositis (PM/DM) seen at the University of Pittsburgh and affiliated hospitals since 1975, 21 of 100 tested positive for the anti-Jo-1 antibody. Sixteen of the 21 patients were women and 18 were white. Fifteen had adult PM, 4 had myositis in overlap with scleroderma, and 2 had adult DM. Evidence of interstitial lung disease was found in 12 of 18 anti-Jo-1 positive patients (67%), but in only 15 of 79 anti-Jo-1 negative patients (19%) (P less than 0.0002). The 21 anti-Jo-1 positive patients were divided into 3 separate groups based on the observed articular findings. Four patients had a deforming, predominantly nonerosive arthropathy with subluxations of the distal interphalangeal joints, especially the thumbs. Eight patients had a nondeforming arthropathy primarily affecting the small joints of the hands, wrists, shoulders, and knees. Those with deformities had a longer duration of arthritis compared with those with nondeforming arthropathy (mean 14.5 years versus 3.3 years). Nine anti-Jo-1 positive patients had no joint arthropathy. Three of 4 patients with deformities have required articular reconstructive surgery for subluxation, with 2 having associated subcutaneous calcinosis. PMID- 2242063 TI - Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. AB - Procainamide and hydralazine inhibit T cell DNA methylation and induce autoreactivity in cloned CD4+ T cells. These drugs also induce an autoimmune syndrome, suggesting a possible relationship between DNA hypomethylation, T cell autoreactivity, and certain autoimmune diseases. To test this relationship, DNA methylation was studied in T cells from patients with rheumatoid arthritis and patients with systemic lupus erythematosus, and was found to be impaired. These results support a relationship between DNA hypomethylation and some forms of autoimmune disease. PMID- 2242064 TI - Association of labial salivary gland histopathology with clinical and serologic features of connective tissue diseases. AB - Focal sialadenitis is now widely accepted as an objective criterion for the oral component of Sjogren's syndrome (xerostomia). We investigated the association between labial salivary gland histopathologic changes and the clinical and serologic features of 192 patients with suspected connective tissue disorders. A retrospective review of the medical records of all patients was performed, and historical, physical, laboratory, histologic, and roentgenographic data were abstracted. Each patient had undergone labial salivary gland biopsy as part of a rheumatologic evaluation. There were significant associations between positive findings on lip biopsy and the presence of keratoconjunctivitis sicca (P = 0.013), positive antinuclear antibodies (titer greater than or equal to 1:80) (P = 2 x 10(-8)), and positive Ro antibodies (P = 1 x 10(-8)). However, sicca symptoms and glandular enlargement were not statistically associated with positive findings on lip biopsy. Features predictive of a positive lip biopsy included Ro antibodies (P = 0.914), keratoconjunctivitis sicca (P = 0.700), and positive antinuclear antibodies (P = 0.590). PMID- 2242065 TI - Functional studies of soluble low-affinity interleukin-2 receptors in rheumatoid synovial fluid. AB - Since abnormal regulation of interleukin-2 (IL-2) has been demonstrated in rheumatoid arthritis (RA), the functional role of low-affinity soluble IL-2 receptors (sIL-2R) purified from RA synovial fluids (SF) was studied. Picomolar levels of sIL-2R were detected in RA SF using an enzyme-linked immunosorbent assay. Levels were higher in serum and SF from RA patients than in controls (P less than 0.001) and higher in RA SF than in paired RA serum (P less than 0.01). Soluble IL-2R from RA SF had estimated molecular weights of 40-50 kd and 80-100 kd by gel filtration analysis. The 80-100-kd peak is likely to be a dimer of the 40-50-kd peak, since a single 45-kd peak was found after elution from sodium dodecyl sulfate-polyacrylamide gels. Since inhibitory activity for lymphocyte proliferation was found in the 80-100-kd range, the sIL-2R were purified with an anti-CD25 affinity column and further analyzed. The purified fractions did not interfere with the proliferation of mitogen-stimulated lymphocytes or with the binding of radiolabeled IL-2 to CTLL-2 cells, although direct binding of IL-2 was demonstrated. The affinity of sIL-2R from RA SF for binding IL-2 was in the range of 25 nM, which is similar to the affinity of sIL-2R purified from a human T cell clone, indicating that both sIL-2R are low-affinity receptors for IL-2. We conclude that the concentration and binding affinity of low-affinity sIL-2R purified from RA SF render them unable to interfere with IL-2-related activities. PMID- 2242066 TI - Interleukin-1-induced interleukin-6 is required for the inhibition of proteoglycan synthesis by interleukin-1 in human articular cartilage. AB - Cartilage from normal controls, patients with osteoarthritis, and patients with rheumatoid arthritis produced no interleukin-6 (IL-6) in culture. However, IL-1 induced massive production of IL-6 (up to 135 ng/ml) in cartilage from all 3 sources, in a dose-dependent manner (in some cases, a peak value was reached). The levels of induced IL-6 were similar to those found in rheumatoid arthritis synovial fluid. At IL-1 concentrations that induced almost complete inhibition of proteoglycan (PG) synthesis, IL-6 production could still be increased considerably. Exogenous IL-6 inhibited PG synthesis by up to 25%. IL-1-induced inhibition of PG synthesis was reversed by antibodies against recombinant human IL-6. These results suggest that IL-6 is required for the IL-1-induced inhibition of PG synthesis. PMID- 2242067 TI - Dermal mast cell degranulation in systemic sclerosis. AB - Paired biopsy samples from involved and uninvolved skin were obtained from 19 patients with generalized scleroderma (11 with early, progressive disease and 8 with late, improving disease). Skin biopsy samples were double stained for mast cell granules and for mast cell membrane. The number of mast cells was increased in patients with systemic sclerosis (SSc), in both involved and uninvolved skin and in both early and late disease. There was an increase in the number of degranulated mast cells in the involved skin of patients with both early and late disease and in the not-yet-involved skin of patients with early disease; however, there was no increase in the number of degranulated mast cells in areas of previously involved but now normal skin of patients with late disease. Increases in mast cell number and degranulation precede clinically apparent dermal fibrosis in SSc. These observations and the absence of mast cell degranulation in regressing skin suggest a participatory role of the mast cell in the clinical progression of skin changes in SSc. PMID- 2242068 TI - Spontaneous rheumatoid-like arthritis in a line of mice sensitive to collagen induced arthritis. AB - Twenty-eight percent of 13-month-old male mice of the high antibody responder line of Biozzi's selection I (HI) spontaneously developed a long-lasting inflammatory arthritis. This disease was clinically and histologically similar to human rheumatoid arthritis. The synovium of joints and some tendons was hypertrophied, with thickening of the synovial cell layer and infiltration by polymorphonuclear and mononuclear leukocytes. In some cases, synovial pannus formation led to destructive damage of articular cartilage and bone. Rheumatoid factor and antinuclear, anti-DNA, and anti-type II collagen (CII) antibodies were often found in the sera of both arthritic mice and clinically normal littermates. The presence of CII autoantibodies in this line of mice suggests that a potentially harmful anti-CII T cell autoimmunity can also develop spontaneously and lead to joint damage. Moreover, HI mice are also susceptible to collagen induced arthritis, while a closely related mouse line (HII) is resistant to both diseases. These data support the hypothesis that collagen-induced arthritis is pathogenetically related both to this spontaneous arthritis and to rheumatoid arthritis. PMID- 2242069 TI - Treatment of psoriatic arthritis with oral 1,25-dihydroxyvitamin D3: a pilot study. AB - We conducted a 6-month open-label trial in which 10 patients with active psoriatic arthritis received 2 micrograms of oral 1,25-dihydroxyvitamin D3 daily. Statistically significant improvement was noted in the tender joint count and physician global impression. Of these 10 patients, 4 had substantial (greater than or equal to 50%) improvement, and 3 had moderate (greater than or equal to 25%) improvement in the tender joint count. Two patients were unable to receive therapeutic doses because of hypercalciuria. High-dose vitamin D may be a useful therapeutic agent for psoriatic arthritis. PMID- 2242070 TI - Nontropical pyomyositis as a cause of subacute, multifocal myalgia in the acquired immunodeficiency syndrome. AB - We report a case of nontropical pyomyositis in a patient with acquired immunodeficiency syndrome and disseminated Mycobacterium avium infection, in which severe myalgia was the presenting symptom over several weeks. Multifocal muscle lesions were identified by gallium scanning and magnetic resonance imaging techniques. The epidemiology, possible pathogenesis, clinical features, diagnostic imaging, and therapy are reviewed. Early suspicion of nontropical pyomyositis in severely immunocompromised patients with "cryptic" myalgia is recommended. PMID- 2242071 TI - Outbreak of spontaneous staphylococcal arthritis and osteitis in mice. AB - Staphylococcus aureus is the most common bacterial species found in association with nongonococcal bacterial arthritis in humans. We present here the first description of spontaneous bacterial arthritis and osteitis in mice. Clinically, the most obvious findings were swelling and/or ankylosis of hindpaws and nodose changes of the tail. The prevalence of arthritis and osteitis ranged from 0% to greater than 50% of the mice studied, depending on the mouse strain. The most prominent histopathologic feature of the arthritis was hypertrophy of the synovial tissue and destruction of cartilage and underlying bone. Most of the S aureus-infected mice displayed an identical phage type, which was also the only S aureus phage type found in skin isolates from clinically healthy mice. However, a few S aureus isolates were not typeable, indicating that an additional strain(s) might cause bacterial arthritis in mice. PMID- 2242073 TI - Subcutaneous cholesterol crystal deposition in the left index finger. PMID- 2242072 TI - Rescue of interleukin-1 activity by leucovorin following inhibition by methotrexate in a murine in vitro system. AB - We have recently shown that methotrexate (MTX) inhibits interleukin-1 (IL-1) activity in vitro. This effect may play an important role in the rapid antiinflammatory action of MTX in rheumatoid arthritis. In the present study, we showed that the inhibition of IL-1 activity in vitro by MTX is dependent on folate pathways since, after the addition of leucovorin, the inhibitory effect of MTX was abolished. These findings may shed more light on the mechanism of action of MTX in rheumatoid arthritis. They also point to the fact that some IL-1 activities may be dependent on intracellular folate pathways. PMID- 2242074 TI - Anticonflict effects of low doses of chloroquine. AB - The effects of low doses (0.125-1 mg/kg) of chloroquine were investigated in a modified Vogel's conflict paradigm and in the light-dark transition box. In the Vogel's conflict paradigm, the compound was found to exert a marked dose dependent increase in the number of shocks accepted by rats in the conflict situation, thus indicating an anxiolytic-like action. In the light-dark transition box, chloroquine increased the number of transitions between the two compartments and the time spent in the lighted area by mice. Thus chloroquine exhibited anticonflict properties in two animal models of anxiety. It is therefore concluded that chloroquine might possess antianxiety-like properties in low doses. PMID- 2242075 TI - [Genotoxicity of a standardized Hypericum extract]. AB - St. John's wort (Hypercum perforatum) contains hypericin and hypericin-like substances as well as flavonoids, of which particularly Quercetin has generated a wide-spread controversial discussion with respect to mutagenic action. The genotoxicity of a standardized aqueous ethanolic Hypericum extract (Hypericum extract Steigerwald, Psychotonin M) was verified in different in-vivo and in vitro testsystems with mammalian cells. The in-vitro investigations were performed with the HGPRT (hypoxanthine guanidine phosphoribosyl transferase) test, UDS (unscheduled DNA synthesis)-test and with the cell transformation test using Syrian hamster embryo cells. Both the in-vitro tests as well as the in-vivo tests--fur spot test of the mouse and the chromosome aberration test with the bone marrow cells of the chinese hamster--were negative, giving completely no indication of a mutagenic potential of Hypericum extract. These investigations lend support to the view that results from bacterial short-term tests are of very limited transferability to human. PMID- 2242076 TI - Effect of zonisamide on serum immunoglobulins. AB - Zonisamide (AD-810) was additionally administered to 19 patients with refractory epilepsy who had been receiving multiple antiepileptic drugs and the effect of zonisamide on serum immunoglobulins was investigated. Zonisamide was administered in daily dose of 200-700 mg (mean 389 mg) for the period of 82-1,470 days (mean 863 days). The serum levels of IgG, IgA and IgM were determined before administration and at intervals of 3 or 6 months over the period of a maximum of 48 months after initiation of administration. There was no significant change in immunoglobulin levels at any time after initiation of zonisamide treatment as compared with the pretreatment levels. No significant correlation was found between the dose or serum concentration of zonisamide and the immunoglobulin levels. PMID- 2242078 TI - Differences in ischaemic myocardial potassium leakage after treatment with the calcium antagonist anipamil or the beta-blocker atenolol. AB - The abilities of the new calcium antagonist anipamil as well as the beta-blocker atenolol to reduce the amount of K+ released into the extracellular space during the first minutes of acute coronary artery occlusion were investigated in anaesthetized pigs. [K+]e was continuously measured epicardially with ion selective electrodes. Immediately after starting an occlusion [K+]e rose steeply from normal plasma levels of 3.5 mmol/l to values about three times as high at the end of the 6-min occlusion. This was reproducible in a second and third occlusion in the untreated control group. In the treatment groups either anipamil (0.5; 1.0 mg/kg) or atenolol (0.3 mg/kg) were injected intravenously 10 min before the second occlusion. Anipamil inhibited K+ loss into the extracellular space dose relatedly and significantly throughout the 6-min occlusion period, whereas atenolol showed no protection. The cardioprotective effect of anipamil was also demonstrated in a third occlusion 60 min post application. This different profile cannot be explained by differences in the ability of the two drugs to lower myocardial oxygen consumption; indeed this was only achieved after atenolol. It is concluded that anipamil exerted a direct protective effect on the cardiac myocyte level during ischaemia. PMID- 2242077 TI - Dose effects of temazepam in transient insomnia. AB - A transient insomnia model, the "first night" effect in the sleep laboratory, was used to assess the dose range for the hypnotic and sleep stage effects of temazepam. 201 healthy, normal subjects (97 men and 104 women), 21 to 49 years old, with no sleep complaints were studied. Each was randomly assigned to receive either placebo, 7.5, 15, or 30 mg temazepam hard gelatin capsules (Restoril) administered double-blind 30 min before bedtime on their first night in the sleep laboratory. Over the 8-h polysomnogram total sleep time and sleep efficiency increased significantly in a linear fashion with increasing doses of temazepam. Sleep tendency was significantly reduced by increasing doses again in a linear manner. Wake time during the sleep period was reduced significantly only by the higher dose. The percentage of stage 1 sleep was reduced and the percentage of stage 2 sleep was increased, each linearly with increasing doses. These data are the first to demonstrate the hypnotic effects of a 7.5 mg dose of temazepam and also support previous studies of 15 and 30 mg temazepam administered to chronic insomniacs. They also illustrate the utility of the "first night" effect as a model of transient insomnia. PMID- 2242079 TI - [Effect of preoral and transdermal insulin preparations on blood glucose concentration in mice]. AB - Effects of oral and transdermal insulin applications on blood glucose concentration were investigated in nonconditioned, healthy mice. Insulin was applied in a special lipid formulation which contained no chemical enhancers or protease inhibitors. In comparison to control applications with same volumes of insulin free lipid formulations significant and reproducible blood sugar lowering effects were found with the insulin-lipid formulation. Additional control applications of the same dosages of oral aqueous insulin solutions differed only slightly to the insulin free lipid formulations. Same dosages of s.c.- and p.o. applications of the insulin-lipid-formulation induced quantitatively comparable blood sugar lowering effects. The maximum oral effects showed dose dependence in a dose range of 0.7 to 9.5 IU/kg bodyweight. Maximal effects after oral application were seen 1-2 h after oral application. Investigations with transdermal insulin applications showed also significant effects in lowering blood glucose concentrations, but these effects were weaker than after oral application and showed a delayed onset. PMID- 2242080 TI - [Transdermal administration of insulin in type II diabetics. Results of a clinical pilot study]. AB - In 6 type II diabetic patients, which showed no satisfactory blood sugar profiles under oral sulfonylurea monotherapy, a placebo controlled cross over pilot trial was performed to evaluate the effect of additive transdermal insulin application. In comparison to the monotherapy with sulfonylurea, the combination with transdermal insulin showed in 4 of the 6 patients a significant reduction of the daily mean blood sugar values as well as a slight increase of insulin serum concentrations. The 2 patients, who had no glucose reductions also showed a slight increase of insulin levels during the combination phase. Relevant adverse reactions were not seen. The results suggest, that in suited patients an improvement of sulfonylurea therapy by combination with transdermal insulin is possible. PMID- 2242081 TI - Radioimmunological determination of fenoterol. Part II: Antiserum and tracer for the determination of fenoterol. AB - A radioimmunological method for the determination of the concentration of fenoterol in biological samples is described. The mixture of antibodies against the enantiomers of fenoterol obtained with the selected hapten shows a high affinity for racemic fenoterol and for the monoiodo125-fenoterol used as a tracer, which is also present as a racemate. The limit of detection of the radioimmunoassay for fenoterol (racemate) in biological samples (plasma, urine) is 10-20 pg/ml. The precision and accuracy of the radioimmunoassay, in the presence of racemic fenoterol, are sufficient for an analysis and meaningful interpretation of samples from human pharmacokinetic studies. A relationship between the cross-reactivity of the antibodies against fenoterol and a preferred conformation of the fenoterol molecule in aqueous solution is discussed. PMID- 2242082 TI - [The effect of flupirtine, various analgesics and muscle relaxants on skeletal muscle tone in the conscious rat]. AB - The influence of the skeletal muscle tone by flupirtine (D-9998, Katadolon; CAS 56995-20-1), some selected analgesics and muscle relaxants was investigated in conscious rats after intraperitoneal administration. Benzodiazepines (diazepam and tetrazepam), baclofen, dantrolene and mephenesine reduced the tone of the skeletal muscle. Opiate analgesics, such as morphine, codeine and tramadol, enhanced the muscle tone. Flupirtine reduced the skeletal muscle tone at doses comparable with its antinociceptive effective doses. In this dose range no sedative side effects as ataxia or decrease of spontaneous motor activity could be observed. The mode of this muscle relaxing effect of flupirtine is not known in all details. It is, however, likely that flupirtine is able to inhibit the mono- and/or polysynaptic reflexes at the spinal level. PMID- 2242083 TI - Antioxidant activity of and interleukin production affected by honey bee venom. AB - Honey bee venom is found to inhibit significantly nonenzymatic lipid peroxidation. It also possesses a considerable hydroxyl radical scavenging activity, evaluated by its competition with dimethyl sulfoxide for HO.. These results, in relation to the in vitro suppression mainly of interleukin-1 production offered by honey bee venom, may further support that antioxidant activity is involved in the anti-inflammatory activity of honey bee venom. PMID- 2242084 TI - Anti-inflammatory activity of some copper(II) complexes. AB - Anti-inflammatory activity of some copper(II) neutral complexes and complexated salts on different animal models of inflammation has been investigated. In a preliminary screening 5 complexes were selected for a more extensive study based on their capacity inhibiting the rat hind paw edema induced by carrageenin. These selected complexes showed inhibitory action on acute and subacute inflammation with an activity degree higher than that of indometacin. They were also effective inhibitors of primary and secondary lesions in the adjuvant-induced arthritis, with an activity similar to phenylbutazone. These complexes had no topical anti inflammatory effect. PMID- 2242085 TI - [Pharmacokinetics of the antirheumatic lonazolac-Ca in humans]. AB - The pharmacokinetics of the non-steroidal, antiinflammatory drug lonazolac-Ca in man was investigated. Lonazolac-Ca (Irritren, arthro akut, Argun-L, Argun-300) (single doses 200 mg or 300 mg) was administered both to healthy, young volunteers and to patients with renal impairment, to elderly and arthritic patients and to nursing women. Serum concentrations were measured for lonazolac and its main serum metabolite M1, and pharmacokinetic characteristics such as Cmax, AUC and t1/2 were calculated after both single and multiple oral doses of film-coated tablets of lonazolac-Ca. In addition also suppositories of lonazolac Ca (single dose 400 mg) were tested after single and multiple administration. In a study in healthy, normal volunteers, total radioactivity in blood was followed after oral and i.v. administration of 14-C-lonazolac-Ca (-Na). Lonazolac and M1 generally showed a biphasic pattern of elimination, their terminal half-lives being both ca. 6 h in young volunteers. In elderly patients the terminal half life was about twice as long. Nevertheless, no accumulation of lonazolac on multiple dosing was observed in either volunteers or patients due to the rapid alpha-phase. However, some accumulation occurred for the (pharmacologically inactive) M1 in elderly patients and in patients with renal impairment. Serum profiles were lower and flatter after administration of suppositories as compared to oral administration. Lonazolac concentrations in synovial fluid were about half of those in serum, no lonazolac could be found in breast milk although there was some transfer of M1. PMID- 2242086 TI - Development of a high performance liquid chromatography method for the simultaneous measurement of prednisone and prednisolone. AB - An improved high performance liquid chromatographic assay (HPLC) is presented for the quantitative determination of prednisone and its main metabolite prednisolone. This HPLC assay, employing a UV-detector and dexamethasone as an internal standard, provides a selective and sensitive determination of glucocorticoids in plasma. The advantage of this method is the possibility of simultaneously measuring exogenic and endogenic glucocorticoids. The lower limit of quantification is 5 ng/ml. PMID- 2242087 TI - In vivo studies with the stabilized epoprostenol analogue taprostene. Effects on platelet functions and blood clotting. AB - Like the native epoprostenol (prostacyclin, PGI2), the oxacyclic epoprostenol analogue taprostene affects platelet functions. In the rat taprostene inhibited in vivo induced ADP aggregation after i.v. bolus injection, i.v. infusion, s.c. and p.o. application with ED50 values of 4.6 micrograms/kg, 0.36 microgram/kg/min, 190 micrograms/kg and approximately 760 micrograms/kg, respectively. In vivo induced collagen aggregation was inhibited with an ED50 value of 17.1 micrograms/kg i.v. Referring to both bolus injection and i.v. infusion, taprostene was about 3 times less active than the native prostacyclin, but the antiaggregatory effect of taprostene was longer lasting. 5,6 Dihydroepoprostenol inhibited ADP-induced aggregation with an ED50 value of 3 micrograms/kg/min, being 10 fold less active than taprostene. Whereas epoprostenol induced a rebound effect by increasing in vivo aggregation after the end of infusion, no such effect could be seen after taprostene. In the mouse s.c. and p.o. application of taprostene inhibited aggregation with the same efficacy as in the rat. Intra-arterial infusion of taprostene into the rabbit inhibited ADP-induced aggregation ex vivo with an ED50 value of 0.49 micrograms/kg/min. An increased bleeding time was observed in rats in doses of 2.15 micrograms/kg i.v. and higher, corresponding to the antiaggregatory dose range of taprostene. Administered alone, taprostene did not prolong the clotting time in rats. However, in heparinized rats, the heparin-induced prolongation of clotting time was further increased by taprostene with a threshold dose of 21.5 micrograms/kg (= heparin sparing effect). PMID- 2242088 TI - Topical tolerability of salmon calcitonin assessed by mucociliary transport velocity investigation. AB - The topical tolerability of an intranasal salmon calcitonin spray preparation, of the excipients alone and of sodium taurocholate has been studied by assessment of the mucociliary transport velocity (MTV) on the frog's palate. The rate of mucus transport was investigated in 3 groups of animals (Rana esculenta; 6 frogs per group) in basal conditions and after a challenge with a salmon calcitonin intranasal spray preparation, with the excipients and with sodium taurocholate, respectively. The salmon calcitonin intranasal spray preparation and the excipients did not affect the mucociliary transport velocity on the frog's palate. On the contrary, sodium taurocholate produced severe impairments in the mucociliary transport velocity and histological lesions of the epithelial layer of the frog's palate. The comparison among the mean values of the mucociliary transport velocity before and after treatments showed a significant difference between controls and sodium taurocholate groups (p less than 0.05) as well as among the groups treated with sodium taurocholate versus salmon calcitonin and versus the excipients alone of the calcitonin preparation (p less than 0.05). These findings provide evidence that the salmon calcitonin intranasal spray preparation tested in the present ex vivo model does not affect the mucociliary transport velocity in the frog's palate, while this is markedly affected by sodium taurocholate. The use of sodium taurocholate as a promoter of absorption in intranasal preparations should thus be reconsidered. PMID- 2242089 TI - Factors determining the relationship between renal and hepatic excretion of xenobiotics. AB - Relation between kidney and liver in the excretion of drugs depends on the physicochemical properties of each substance tested. The calculations of this relationship are based on a so-called rank coefficient (0-100) calculated from molecular weight, lipophilicity, degree of dissociation under physiological conditions, and protein binding rate. The results of the correlation between one of these physicochemical values and drug elimination were stochastically. Experiments were performed with 9 test substances which were distinctly different concerning their physicochemical features. Substances with a rank coefficient less than 20 (low molecular weight, low lipophilicity, preferentially ionic at pH 7.4) are eliminated effectively via the kidney. Compounds having an intermediate rank coefficient (40-60) were quantitatively excreted into urine as well. For drugs with high ranks greater than 60 (high values of molecular weight, protein binding, and lipophilicity, almost exclusively nonionic), renal excretion can be neglected. Quite inverse relations between ranks and hepatic excretion have been found: low ranks indicate an ineffective secretion of the respective drug into bile. With increasing ranks (40-60), biliary excretion increases and reaches a maximum (approximately 40% of supply). This maximum is caused by limited hepatic blood flow and by the capacity of hepatic uptake carriers. Blockade of one elimination pathway (bilateral nephrectomy or bile duct ligation) is followed by a sufficient compensation of drug excretion via the alternative elimination route only, if the test substance belongs to the intermediate group (ranks between 40 and 60). For substances with high or low ranks a compensation of drug excretion can be excluded. PMID- 2242090 TI - Methodical and ethical aspects of nucleic acid diagnostics. A review. AB - Aside from the established enzymatic and immunodiagnostic procedures, an increasing number of diagnostic procedures for nucleic acid detection--i.e. for the detection of the primary genetic information--has been developed in recent years. For the routine use of these diagnostic procedures in central analytical laboratories or by the general practitioner, automated DNA analysis methods with integrated highly sensitive detection systems have been developed. The most important objective of these developments--aside from the elucidation of the type of genetic defect on the molecular level through basic research--is the generation of a quantitative nonradioactive signal in corresponding analyzers. Detection methods using the ELISA principle as quantifiable reporter system- analogous to the automatic immunodiagnostic procedures--have hence been developed in recent years. Owing to the increasing importance of this analysis procedure alternative to the detection of bioactive low molecular weight substances or proteins--i.e. nucleic acid diagnostics--the following is an attempt to provide a survey of the methods and possibilities of application. Moreover, possibilities for nonradioactive signal generation and amplification will be presented. The chances and risks of genome diagnostics will be discussed in a final section. PMID- 2242091 TI - Abnormalities in sex hormones are a risk factor for premature manifestation of coronary artery disease in South African Indian men. AB - The relation between sex hormone levels and myocardial infarction was studied in a case-control study among 117 Indian men with myocardial infarction aged 30-60 years and in 107 healthy Indian male controls. The patients and controls were further divided into subsets defined by age in decades. In the total patient population, testosterone concentration was significantly lower than in the controls (P less than 0.01), whilst oestradiol (P less than 0.0005) and the oestradiol to testosterone ratio (P less than 0.0005) were significantly higher. Multivariate stepwise logistic regression analyses demonstrated that free testosterone index, the free oestradiol index, and the oestradiol to testosterone ratio were significantly associated with myocardial infarction, and that this association was independent of age, body mass index, smoking and serum lipids. Further analyses according to age subsets revealed that compared to respective control groups, patients in the 4th decade had both significant hypotestosteronaemia and hyperoestrogenaemia, whereas in patients of the 5th decade significant differences in total and in the calculated free oestradiol index were noted, and in the 6th decade a significant difference was detected only in the free oestradiol index. Hence, we conclude that aberrations in endogenous sex hormones are significantly associated with myocardial infarction, and that this association appears to be strongest in young men and diminishes with age, suggesting that these disturbances in sex hormones may be associated with premature manifestation of coronary artery disease. PMID- 2242092 TI - Arterial injury-induced smooth muscle cell proliferation in rats is accompanied by increase in polyamine synthesis and level. AB - Proliferation of smooth muscle cells (SMC), enhancement of polyamine biosynthesis and increase in polyamine level in response to deendothelialization in the rat aorta were studied. [3H]Thymidine incorporation into SMC in aortas denuded with a balloon catheter began 25 h after injury, and maximal incorporation occurred 33 37 h after injury. Afterwards, [3H]thymidine incorporation declined, approaching the baseline level, but was slightly higher than that of sham-operated controls until 14 days after injury. Intimal thickening started 7 days after injury, and peaked at 21 days. Prior to these proliferative changes in aortic SMC, a rapid and transient increase in ornithine decarboxylase (ODC) activity was observed within 8 h after injury. There was no significant difference in ODC activity between injured and intact aortas after 4 days. The levels of polyamines, putrescine, spermidine, and spermine increased and were maximal at 48 h after injury, 8.1, 3.4 and 1.4 times the control levels, respectively. Increased levels of polyamines, in particular spermidine, continued until 7 days after injury. These results suggest that the enhancement of polyamine synthesis and the increased polyamine content of the aorta play important roles in the proliferation of SMC and in the development of intimal thickening, particularly in the initial proliferative response of medial SMC after deendothelialization. PMID- 2242094 TI - Characterization of LDL binding in TR 715-19 cells. A high capacity, stable line for evaluating the binding of LDL to the human LDL receptor. PMID- 2242093 TI - Effect of centrifugal force and catecholamines on glycosaminoglycans synthesis of vascular smooth muscle cells in culture. AB - To evaluate the effect of hypertension on glycosaminoglycan (GAG) synthesis, cultured vascular smooth muscle cells (CVSMCs) from the aorta of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were exposed to centrifugal forces and catecholamines. GAG synthesis of CVSMCs was measured by the incorporation of [3H]glucosamine into GAGs which were secreted into the culture medium for 24 h. Basal level of GAG synthesis was much higher in SHR than in WKY, when expressed in terms of DNA contents. When exposed to centrifugal force, CVSMCs from rats of both strains synthesized more GAGs. GAG synthesis was enhanced by both noradrenaline (NA) and adrenaline (Ad) in WKY. The enhanced GAG synthesis in WKY by NA or Ad was prevented by pretreatment with propranolol, but not prazosin. In SHR, NA and Ad did not enhance GAG synthesis at this concentration of catecholamines. However, the effects of propranolol or prazosin on GAG synthesis in SHR, when incubated with either NA or Ad, were compatible with the phenomena observed in WKY. Adding dibutyryl cyclic AMP to the culture medium enhanced GAG synthesis in rats of both strains. These data suggest that not only the mechanical stress of high intra-arterial pressure but also beta receptor stimulation, via increasing cyclic AMP, enhance GAG synthesis of vascular smooth muscle cells in hypertension. PMID- 2242095 TI - Regulation of ACAT activity by a cholesterol substrate pool during the progression and regression phases of atherosclerosis: implications for drug discovery. AB - The regulation of aortic ACAT by a cholesterol substrate pool (CSP) was investigated in a rabbit progression/regression model of dietary-induced atherosclerosis. ACAT activity increased 25-fold during the 10-week progression phase of the study. ACAT activity decreased 8-fold during the 24-week regression phase of the study, however, it was still 14-fold greater than in normal aortas. ACAT activity assayed in the absence vs. the presence of exogenous cholesterol was used as a qualitative measure of the amount of cholesterol in the CSP. The CSP was filled to 28% of capacity in normal aortas, this increased to 75% during the progression phase. By the end of the regression phase, the CSP was filled to 100% of capacity even though serum cholesterol levels had returned to normal. The data are discussed in terms of emerging concepts of intracellular cholesterol trafficking, ACAT inhibitors, and the types of atherosclerotic lesions which may be subject to amelioration by ACAT inhibitors. PMID- 2242096 TI - Plasma lipids, lipoproteins and apolipoproteins in two kindreds of hypobetalipoproteinemia. AB - Plasma lipids and apolipoproteins were quantified in two kindreds of hypobetalipoproteinemia. All affected members were asymptomatic but showed a decrease of 75% in apolipoprotein B and of 69% in LDL-cholesterol. There were no major changes in apo A-I and A-II but all affected family members had reduced levels of apo C-II (by 58%) and C-III (by 59%) without significant decrease in apo C-I and no specific decrease of apo C-III1. Apolipoprotein E is decreased in SDS-PAGE. The plasma level and phenotype of Lp(a) are not affected by HBL, suggesting that a catabolic rather than a synthetic mechanism is responsible for the disease. As shown by density gradient ultracentrifugation, HDL2 particles that contain essentially apolipoprotein A-I, cholesterol and phospholipids represent in affected subjects the major part of HDL. Due to the net reduction of apolipoprotein B-containing particles (VLDL and LDL) as acceptors of lipids in HBL, there is an accumulation of large particles rich in cholesteryl esters. PMID- 2242097 TI - Homocysteine and lipid metabolism in atherogenesis: effect of the homocysteine thiolactonyl derivatives, thioretinaco and thioretinamide. AB - In order to study the relation of homocysteine and lipid metabolism to atherogenesis, rabbits were fed a synthetic atherogenic diet and treated with parenteral thioretinaco (N-homocysteine thiolactonyl retinamido cobalamin), thioretinamide (N-homocysteine thiolactonyl retinamide) or homocysteine thiolactone hydrochloride. All three substances were found to increase dietary atherogenesis. Thioretinaco and thioretinamide increase total homocysteine of serum, but there is no effect of parenteral homocysteine thiolactone hydrochloride on serum homocysteine. The synthetic diet with corn oil significantly lowers serum homocysteine, compared either to baseline chow diet or to the synthetic diet with butter. Atherogenesis is correlated with total homocysteine, total cholesterol and LDL + VLDL cholesterol, and serum homocysteine is correlated with total cholesterol, LDL + VLDL, and HDL cholesterol in the total sample. Both synthetic diets elevate serum cholesterol, triglycerides and LDL + VLDL, but not HDL, compared to baseline values. Thioretinamide causes significant elevation of cholesterol and LDL + VLDL, compared to controls. The results show that increased dietary saturated fat and cholesterol cause deposition of lipids within the arteriosclerotic plaques produced by homocysteine, converting fibrous to fibrolipid plaques. Facilitation of atherogenesis is attributed to the effect of homocysteine on artery wall, either from parenteral homocysteine or from the increased synthesis of homocysteine from methionine, produced by thioretinaco and thioretinamide. PMID- 2242098 TI - The effects of nicotinic acid treatment on high density lipoprotein particle size subclass levels in hyperlipidaemic subjects. AB - Twenty-three consecutive hyperlipidaemic patients were treated with 4 g nicotinic acid daily for 6 weeks. The treatment resulted in the expected reduction of serum very low density (VLDL) and low density lipoproteins (LDL) and in the increase of high density lipoproteins (HDL). The cholesterol concentration of the latter fraction rose by 45%. The HDL fraction was isolated by ultracentrifugation and then subjected to gradient gel electrophoresis (gge), in order to determine the HDL particle size distribution, before and after treatment. The increase of HDL was almost exclusively confined to the largest HDL (gge) subclass HDL-2b, the protein content of which rose by 183%. In contrast, there was about a 25% decrease in the concentration of the smallest HDL(gge) subclasses, HDL-3b and HDL 3c. The levels of HDL-2b and VLDL triglycerides showed a significant inverse correlation before, as well as after, treatment. Multiple partial correlation analysis demonstrated, however, that the nicotinic acid induced increase in HDL 2b concentration showed a highly significant inverse correlation to the decrease in LDL cholesterol, but not to the decrease in VLDL triglyceride levels. Recent studies, in particular those regarding the negative correlation between both the degree and progression of coronary atherosclerosis and the HDL-2b concentration in young male myocardial infarct patients, suggest that the profound increase of HDL-2b levels by nicotinic acid treatment in hyperlipidaemic patients might be of considerable importance in the protection of coronary atherosclerosis. PMID- 2242099 TI - Rheological properties and membrane fluidity of red blood cells and platelets in primary hyperlipoproteinemia. AB - Lipid fluidity of the erythrocyte membrane and intact platelets was examined in 32 male patients affected by types IIA, IIB and IV primary hyperlipoproteinemia and 15 control subjects. Lipid fluidity was determined by fluorescence polarization using two probes: DPH and TMA-DPH which are localized in different lipid areas of the cell membrane. Classical haemorheological tests were also performed including plasma viscosity, whole blood viscosity and erythrocyte aggregation. As compared to a control group, plasma viscosity and whole blood viscosity at low shear rate was significantly increased in types IIB and IV, but not in type IIA patients. In contrast, the increase in erythrocyte aggregation was significant in all HLP types. Concerning lipid fluidity, the results recorded with red cells and platelets were not significantly different for type IIA HLP compared to the control group. In contrast, erythrocyte membranes from patients with types IIB and IV HLP had a significantly higher level of fluidity in lipid regions characterized by TMA-DPH. Using DPH as a fluorescent probe, identical results were only noted in type IIB patients. Regarding intact platelets of IIB and IV patients, an increase in lipid fluidity was noted for two fluorescent probes. These findings suggest that HLP associated erythrocyte and platelet fluidity alterations are not related to hypercholesterolemia but to the triglyceride level. PMID- 2242100 TI - Internal elastic membrane in the internal mammary and left anterior descending coronary arteries and its relationship to intimal thickening. AB - The internal mammary artery (IMA) is less prone to intimal thickening than coronary arteries and is routinely used in coronary bypass surgery. To resolve whether morphologic differences can explain why IMA develops less intimal thickening, morphometric measurement of the left anterior descending coronary artery (LAD) and IMA was carried out in 62 autopsies from individuals of various age groups. The amount of intimal thickening, the degree of folding of the internal elastic membrane, and media thickness were estimated by appropriate indices. Intimal thickening of LAD was more marked, occurred earlier and could be demonstrated even below one year of age, but was not found before 21 years of age in the IMA. A fold-index of the internal elastic membrane was significantly higher in the IMA than in the LAD and correlated negatively with an intimal thickening index in both arteries (P less than 0.0001 for both). The fold-index decreased with age, most markedly in LAD. Negative correlation was also found between a media thickness index and the intimal thickening index in LAD (P less than 0.02). The fold-index may indicate the magnitude of tangential intimal tension during life and may be of significance for development of intimal thickening and atherosclerosis. Lower fold-index may in part explain the propensity of atherosclerosis in LAD compared with IMA. Also, reduced fold-index with age accompanied the occurrence of atherosclerosis with age. PMID- 2242101 TI - Dose-dependent effect on serum cholesterol and apoprotein B concentrations by consumption of boiled, non-filtered coffee. AB - The effects of boiled coffee (BC) and filtered coffee (FC) on serum lipoproteins were compared in 41 healthy subjects whose serum cholesterol concentration was less than 7 mmol/l. The subjects consumed in random order BC and FC for 4-week periods in a crossover design. The individual daily consumption ranged from 2 to 14 cups (mean 5.7 cups per day) and was similar during both study periods. The serum total and LDL-cholesterol and apoprotein B concentrations were higher (P less than 0.001) and HDL-cholesterol lower (P less than 0.05) after BC than after FC. Bodyweight, apoprotein A-I and triglycerides remained unchanged. In the 16 subjects who consumed coffee less than 5 cups per day the difference in serum total cholesterol between the BC and FC periods was non-significant (P = 0.16). The differences in serum total cholesterol and LDL-cholesterol between the periods showed significant linear correlations with the amount of coffee consumed daily (r = 0.52, P less than 0.001 and r = 0.33, P less than 0.05, respectively) but no association was found between the difference in HDL-cholesterol and the amount of coffee (r = 0.14, P = 0.39). The results indicate a dose-dependent increasing effect on serum total and LDL-cholesterol and apoprotein B concentrations of boiled coffee. PMID- 2242102 TI - Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular manipulation. PMID- 2242103 TI - Psychotherapy training for the psychiatrist of the future. AB - There is uncertainty about the future role of psychodynamic psychotherapy in psychiatric practice and education. The Association for Academic Psychiatry and the American Association of Directors of Psychiatry Residency Training formed a joint task force to review the issue. It developed a rationale for continued training in expressive psychotherapy and a model curriculum for such training that is both effective and realistic in terms of the diverse demands and structures of modern residencies. A minimum curriculum was also designed for resource-poor programs. PMID- 2242104 TI - Drug therapy: The diagnosis and management of insomnia. PMID- 2242105 TI - Continuous spinal anesthesia with a microcatheter technique: preliminary experience. PMID- 2242106 TI - Phenobarbital for febrile seizures--effects on intelligence and on seizure recurrence. AB - Phenobarbital is widely used in the treatment of children with febrile seizures, although there is concern about possible behavioral and cognitive side effects. In 217 children between 8 and 36 months of age who had had at least one febrile seizure and were at heightened risk of further seizures, we compared the intelligence quotients (IQs) of a group randomly assigned to daily doses of phenobarbital (4 to 5 mg per kilogram of body weight per day) with the IQs of a group randomly assigned to placebo. After two years, the mean IQ was 7.03 [corrected] points lower in the group assigned to phenobarbital than in the placebo group (95 percent confidence interval, -11.52 to -2.5, P = 0.0068 [corrected]). Six months later, after the medication had been tapered and discontinued, the mean IQ was 5.2 points lower in the group assigned to phenobarbital (95 percent confidence interval, -10.5 to 0.04, P = 0.052). The proportion of children remaining free of subsequent seizures did not differ significantly between the treatment groups. We conclude that phenobarbital depresses cognitive performance in children treated for febrile seizures and that this disadvantage, which may outlast the administration of the drug by several months, is not offset by the benefit of seizure prevention. PMID- 2242107 TI - Clinical utility of serum tests for iron deficiency in hospitalized patients. AB - Serum iron and ferritin measurements lack the requisite sensitivity and/or specificity to accurately diagnose iron deficiency. To determine their utility in hospitalized patients, the authors compared the results of these tests with the presence of stainable iron in bone marrow aspirates of 301 patients. Forty (13.3%) had absent marrow iron. The serum diagnosis of iron deficiency was accepted on the basis of the following: iron less than 11 mumol/L, total iron binding capacity (TIBC) greater than 45 mumol/L, transferrin saturation (%Sat) less than 0.20, and ferritin less than 13 micrograms/L for females and less than 25 micrograms/L for males. Using these criteria, iron deficiency was correctly diagnosed by serum iron in 41%, TIBC in 84%, %Sat in 50%, and ferritin in 90% of the patients. The serum ferritin is clearly the only useful serum test for diagnosing iron deficiency in hospitalized patients but is limited by a low sensitivity. The bone marrow examination is the most sensitive test for diagnosing iron deficiency in hospitalized patients. PMID- 2242108 TI - Dietary protein source and plasma lipid profiles of infants. AB - Total cholesterol and triglyceride concentrations were measured in plasma samples taken at 4 and 8 weeks of age from 40 full-term infants who had been fed either human milk or one of three formulas containing casein-to-whey ratios of 82:18, 66:34, or 50:50 to investigate whether dietary protein influenced the development of plasma lipid profiles. Infants fed the formula with the casein-to-whey ratio of 82:18 had significantly higher plasma cholesterol levels at both 4 and 8 weeks of age compared with other groups of infants (P less than .05). Infants fed the high-casein formula also showed an increase in plasma cholesterol levels with time (P less than .001). Plasma triglyceride concentrations decreased as concentration of casein decreased (P less than .05) among the formula-fed groups and increased with time. Infants fed human milk had plasma triglyceride concentrations similar to those infants who had been fed the 82:18 formula at 4 weeks of age; however, triglyceride concentrations eventually fell and were similar to those concentrations in infants who had been fed the 50:50 formula at 8 weeks of age. Results indicate that constituent lipids of human milk or formulas were not determining factors for changes observed in plasma cholesterol levels and triglyceride concentrations among groups. Since formulas differed only in proteins and their constituent amino acids, further investigation of the impact of dietary protein (amino acids) on development of blood lipid profiles in infants is warranted. PMID- 2242109 TI - The efficiency of two-phase designs in prevalence surveys of mental disorders. AB - A two-phase survey of mental disorders uses a screening test to identify possible cases, thereby reducing the resources devoted to interviewing those not having the condition of interest. It is demonstrated using a mathematical model that in situations likely to be encountered in practice a two-phase design may lead to an increase in the efficiency of prevalence rate estimation, and also to an improvement in the efficiency of case detection. However, in certain applications the modest gain in efficiency may not warrant the additional complexity of a two phase approach to data collection. Data from a survey of mental disorders in Edmonton, Canada, which collected information on 3258 community residents using the Diagnostic Interview Schedule and the General Health Questionnaire, are used to demonstrate how two-phase methods would have changed the efficiency of an actual survey. PMID- 2242110 TI - Guns and violence in Australia. PMID- 2242111 TI - Neoplasia masquerading as periapical infection. AB - Seven examples of neoplasia which presented as periapical radiolucencies are described. These were all initially treated for presumed periapical infection. The atypical features that should alert dentists to the possibility of a tumour presenting in this manner are: a vital tooth with minimal caries, root resorption and an irregular radiolucent outline, tooth mobility in the absence of generalised periodontal disease, regional nerve anaesthesia, and failure to respond to good endodontic therapy. All material removed at the time of apical surgery must be examined histologically to prevent neoplasia being overlooked. PMID- 2242112 TI - Variant t(2;18) translocation in a Burkitt conversion of follicular lymphoma. PMID- 2242113 TI - Dyspepsia in general practice. PMID- 2242114 TI - Characterization with a simple clotting assay of the tissue factor inhibiting activity in serum. AB - The serum inhibiting activity on tissue factor (TFI) was evaluated as follows: normal human serum was incubated at room temperature with highly diluted rabbit brain thromboplastin (TF) and calcium ions; after 30 min. rabbit brain cephalin, calcium and normal human plasma were added to a small aliquot of TF/serum mixture; the clotting time at 37 degrees C was then recorded. With this assay TFI activity is proportional to the serum level; it is low for incubation periods shorter than 30 min., is missing at TF concentrations higher than 8%, is strictly connected to the presence of F VII and F Xa in the serum sample, depends upon the presence of calcium ions and finally, is independent of antithrombin III. This inhibiting activity also seems to be saturable and reversible. PMID- 2242116 TI - Congenital cataracts. PMID- 2242115 TI - Calcium leucovorin and 5-fluorouridine cytotoxicity. AB - The action of fluoropyrimidine (FP) drugs at thymidylate synthase (TS) is associated with enhanced chemotherapeutic response. Calcium leucovorin (CF) increases the cytotoxicity of the FP drugs, 5-fluorouracil and 5 fluorodeoxyuridine, in human laryngeal carcinoma HEp-2 cells by directing the action of these drugs at TS. Thus, the effect of CF on the cytotoxicity and site of action of the FP, 5-fluorouridine (FUrd), was investigated in HEp-2 cells. The cytotoxicity of FUrd was unaffected by CF. Moreover, CF was unable to alter the growth-limiting target of FUrd to TS. HEp-2 cells convert FUrd to FdUMP, the FP metabolite that is the direct inhibitor of TS; thus, the inability of CF to modulate FUrd action is not due to lack of inhibitor formation. In addition, greater than 90 percent of TS activity is inhibited at concentrations of FUrd that inhibit HEp-2 cell growth by 50 percent. Thus, while TS is significantly inhibited by FUrd, it is not the growth-limiting target of this drug. It is likely that the RNA-directed effects of FUrd are so extensive that CF, which maximizes TS-directed action, is ineffective at reducing the cytotoxicity further. An approach to overcoming the RNA-directed effects of FUrd is suggested. PMID- 2242117 TI - Surgery and Salmonella. PMID- 2242118 TI - Psychological treatment for depressive disorder. PMID- 2242119 TI - Is there a preference for different ways of performing faecal occult blood tests? AB - Low compliance with faecal occult blood screening reduces the power of clinical trials, potential benefit, and efficiency. It has been proposed that the faecal manipulation required to perform conventional guaiac based tests may be an important factor in low compliance. The aim of this study was to evaluate whether use of a new method (vehicle) of stool collection for the faecal occult blood guaiac test would be preferred to the established standard. A novel self interpreted test, Early Detector (ED), requires the subject to apply a guaiac/peroxide spray to a stool sample collected simply by wiping the anus with a specimen pad. To determine whether this method would be preferred to the stool manipulation required by Haemoccult (HO) and to compare test validity, employees at a London company were invited to use both tests. Eight-hundred and fifty-seven subjects were shown both tests. Before use, 48% indicated a preference for the method of Early Detector; 24% chose Haemoccult (p less than 0.001), while 28% indicated no immediate preference. Seven-hundred and one performed both tests. After use, 74% preferred ED; 5% preferred HO (p less than 0.001); 21% had no preference (NP). The preference for the ED test method was consistent by sex categories, age groups and occupational class. Logistics, aesthetics, and immediacy of results were the main reasons indicated for choosing ED. Whether the preference for ED could result in higher compliance remains to be proven. Its high positivity (14%), however, would preclude its use as a sole test to determine the need for endoscopic and/or radiologic investigation in the screened patient. PMID- 2242120 TI - [Nicolau syndrome after ketazon injection]. AB - Nicolau syndrome is a rare complication, which occurs after intramuscular injections of various drugs, particularly antirheumatic drugs. During one year, the authors observed this syndrome in three patients, who had received intramuscular injections of Ketazon. The aetiology of the syndrome is not yet known, but it is often caused by accidental intraarterial injections of the drug. Since there is no specific therapy for the syndrome, the authors insist on the possibility of preventing it. PMID- 2242121 TI - Radiography degrees and medical physicists. PMID- 2242122 TI - X-ray requests from nurse practitioners. PMID- 2242123 TI - Public-sector health spending may aid competitiveness. PMID- 2242124 TI - Undifferentiated vascular endothelial cells in coronary allograft atherosclerosis. PMID- 2242125 TI - Complications of i.v. therapy: Vialon vs. Teflon. PMID- 2242126 TI - Duration of meningitis therapy. PMID- 2242127 TI - Ultrasound mammography for the diagnosis of a ruptured breast implant. PMID- 2242128 TI - Removal of buccal fat pad by liposuction. PMID- 2242129 TI - Plasma progesterone concentrations in llamas. PMID- 2242130 TI - Fluoroquinolone drug interactions. PMID- 2242131 TI - Using the patient's history to estimate the probability of coronary artery disease: a comparison of primary care and referral practices. AB - PURPOSE: According to probability theory, the interpretation of new information should depend on the prior probability of disease. We asked if this principle applies to interpreting the history in patients with chest pain. We compared the prevalence of coronary artery disease (CAD) in patients who had similar histories but who came from populations with different disease prevalence. PATIENTS AND METHODS: We studied two high-disease-prevalence populations (patients referred for coronary arteriography) and two low-disease-prevalence populations (patients from primary care practices). We used clinical characteristics of one arteriography population to develop a logistic rule for estimating the probability of coronary artery narrowing. The number of clinical findings determined the logistic score, which was proportional to the prevalence of CAD. RESULTS: The prevalence of CAD was much lower in the primary care population than in the arteriography population, even when patients with similar logistic scores, and thus similar clinical histories, were compared. CONCLUSION: A clinician must take account of the overall prevalence of disease in the clinical setting when using the patient's history to estimate the probability of disease. Failure to observe this caution may lead to errors in test selection and interpretation. PMID- 2242132 TI - Depression and the menopause. PMID- 2242133 TI - Genital warts. PMID- 2242134 TI - Vision recovery in amblyopia. PMID- 2242135 TI - Doppler estimates of cardiac output. PMID- 2242136 TI - A fibrinolytic defect in the respiratory distress syndrome. PMID- 2242137 TI - What did our late paleolithic (preagricultural) ancestors eat? PMID- 2242138 TI - AST/ALT ratio and alcohol abuse. PMID- 2242140 TI - Response to Drs. Cohen and Barkin. PMID- 2242139 TI - The clinical utility of serum tests for iron deficiency in hospitalized patients. PMID- 2242141 TI - Variant t(2;18) translocation in a follicular lymphoma. PMID- 2242142 TI - Terminal care in general practice. PMID- 2242143 TI - The toxic shock syndrome. PMID- 2242144 TI - Central pain. PMID- 2242145 TI - Maternal and fetal screening for antenatal care. PMID- 2242146 TI - Diagnostic tests for Lyme disease. PMID- 2242147 TI - [Hospitalized with a double stigma]. PMID- 2242148 TI - [Pseudohypoparathyroidism; where is the hitch?]. AB - Pseudohypoparathyroidism is a condition in which for some reason the normal effect of PTH in the target organ fails to occur. In the Ia type here described the signal transmission is impaired due to abnormal genetic development of the stimulating G protein (Gs) in the cell membrane resulting in insufficient cAMP production after binding of PTH on the membrane receptor. The failure to occur of the normal PTH effect impairs the calcium homeostasis. In many cases this type of pseudohypoparathyroidism is associated with phenotypical characteristics such as short stature, round face, obesity, brachydactyly, subcutaneous and intracerebral calcifications and sometimes bradyphrenia. Since the Gs protein aspecifically also brings about production of cAMP after binding of other polypeptide hormones to this hormone-specific receptor, several hormone resistances may be present concurrently. PMID- 2242149 TI - Dietary sodium and osteoporosis. PMID- 2242150 TI - The use of topical cyclosporine in high-risk corneal transplants. PMID- 2242151 TI - More on birth order in multiple sclerosis. PMID- 2242152 TI - Comments on task force report on psychiatric residency. PMID- 2242153 TI - Carbamazepine and SIADH. PMID- 2242154 TI - Microcatheters for continuous spinal anesthesia. PMID- 2242155 TI - The carpal tunnel syndrome. PMID- 2242156 TI - Screening for colorectal cancer. PMID- 2242157 TI - Minimum reportable doses from personal monitors. PMID- 2242158 TI - Who should take vitamin supplements? PMID- 2242159 TI - Developing and maintaining a sound undergraduate clerkship curriculum. PMID- 2242160 TI - Multiple bandshift assay: rapid identification and cloning of DNA fragments containing specific protein-binding sites. AB - A new rapid method for the identification and cloning of DNA fragments containing specific protein-binding domains is based on the common bandshift assay. Cloned DNA is digested with a restriction endonuclease recognizing a particular 4-bp sequence, an aliquot of this digest is end-labelled and used in protein binding reactions with and without protein extract. The binding reactions are then loaded onto nondenaturing polyacrylamide gel. The main portion of the digest is run in a parallel lane and serves as a source of fragments for cloning. Autoradiography of the wet gel reveals loss in intensity of some bands from the restriction digest incubated with the protein extract. DNA fragments corresponding to these bands are cut out from the gel; DNA is eluted and cloned in the M13 vector, thus allowing rapid and simple sequencing of the inserts. The method, termed multiple bandshift assay, is especially useful when screening relatively long DNA fragments (of several kb) for potential protein-binding domains. The procedure was used to study interaction of HeLa-cell nuclear proteins with a 5.2-kb downstream region of pseudorabies virus immediate-early gene (C. Vlcek, Z. Kozmik, V. Paces, S. Schirm and M. Schwyzer, unpublished). PMID- 2242161 TI - gm: a practical tool for automating DNA sequence analysis. AB - The gm (gene modeler) program automates the identification of candidate genes in anonymous, genomic DNA sequence data. gm accepts sequence data, organism-specific consensus matrices and codon asymmetry tables, and a set of parameters as input; it returns a set of models describing the structures of candidate genes in the sequence and a corresponding set of predicted amino acid sequences as output, gm is implemented in C, and has been tested on Sun, VAX, Sequent, MIPS and Cray computers. It is capable of analyzing sequences of several kilobases containing multi-exon genes in less than 1 min execution time on a Sun 4/60. PMID- 2242162 TI - The single-minded gene of Drosophila is required for the expression of genes important for the development of CNS midline cells. AB - The single-minded (sim) gene of Drosophila encodes a nuclear protein that plays a critical role in the development of the neurons, glia, and other nonneuronal cells that lie along the midline of the embryonic CNS. Using distinct cell fate markers, we observe that in sim mutant embryos the midline cells fail to differentiate properly into their mature CNS cell types and do not take their appropriate positions within the developing CNS. We further present evidence that sim is required for midline expression of a group of genes including slit, Toll, rhomboid, engrailed, and a gene at 91F; that the sim mutant CNS defect may be largely due to loss of midline slit expression; and that the snail gene is required to repress sim and other midline genes in the presumptive mesoderm. PMID- 2242164 TI - Uniforms vs. business clothes for occupational health nurses. A needs survey. AB - The occupational health nurses' role has grown to that of manager. They work to achieve corporate goals such as cost containment through promotion of wellness. They are well suited to the changing technology of the corporate community. The changing role of the occupational health nurse has been accompanied by a change in what they wear to work. Uniforms are no longer standard, and business clothes are increasing in popularity. A uniform committee at AT&T Bell Laboratories was formed to assess the need for change in clothing. A non-random survey was used to investigate what others in the field were wearing. Nurses from 89 companies in eight states completed a total of 274 questionnaires. As a result of the survey, nurses at AT&T Bell Laboratories were given the option of wearing a uniform, street clothes and laboratory coat, or just street clothes as job function indicated. PMID- 2242163 TI - Regulation of the dnaQ gene of Escherichia coli in mutants expressing the SOS regulon constitutively. AB - Current models for the mechanism of SOS mutagenesis in E. coli propose the involvement of a new or modified DNA polymerase III holoenzyme in error-prone replicative bypass of bulky DNA lesions assuming an inhibited or excluded 3'--- 5' proofreading exonuclease function of DNA polymerase. By promotor fusion to galK, gene fusion to lacZ and Sl analysis the in vivo regulation of dnaQ coding the proofreading subunit of DNA polymerase III holoenzyme was analyzed under conditions of induced or constitutive SOS expression. The results presented here clearly show that, at least on the level of gene expression no regulatory event seems to contribute to the assumed decrease of proofreading activity during SOS mediated error-prone bypassing of bulky lesions. On the contrary, an increase in dnaQ gene expression was observed following treatment with some SOS inducing agents which produces bulky DNA lesions. PMID- 2242165 TI - Policies and practices used for the safe handling of antineoplastic drugs. AB - There is increasing evidence that exposure to antineoplastic drugs in the workplace has definite, measurable effects on health care workers. The literature supports the theory that use of proper protective practices and equipment while handling antineoplastic drugs will provide adequate protection from the effects of these agents. Many of the hospitals, physicians' offices, and health care agencies surveyed did not have comprehensive policies outlining safe practices and procedures when handling antineoplastic drugs. Use of gloves was the only consistently used method of self protection in any facility that responded to the survey. In spite of the known potential dangers associated with exposure to these drugs, the literature supports the theory that many health care workers still do not use available protective equipment and procedures. Research is imperative to determine the exact long term effects of exposure to antineoplastic drugs by health care workers and to develop ways to ensure proper, consistent use of safety measures. PMID- 2242166 TI - Understanding why some employees ignore worksite health promotion efforts. Refocusing the issue. AB - Corporations are beginning to examine exactly who is responding to health promotion programs offered at the worksite. Most findings indicate that those employees using most of the health care dollars are the least involved in health promoting efforts. When assessing why certain employees choose not to participate, application of a health promotion model will identify direct and indirect factors associated with this choice. Based on factors identified in the health promotion model, wellness programs are designed to fit the employees' level of readiness to adopt healthy behaviors. The three program levels build upon each other to achieve health promotion. The occupational health nurse has the skills necessary to identify this population which continues to live unhealthy lifestyles. The overall goal is to increase their participation in health promotion. This may be achieved by identifying their needs and designing programs accordingly. PMID- 2242167 TI - Occupational health nursing practice, education, and research. Challenges for the future. AB - The practice of occupational health nursing has expanded enormously and is influenced by company culture and forecasts as well as external factors such as population trends, technology, and the profile of the work force. Future trends include the provision of nurse managed occupational health services. Education and research in occupational health nursing must be strengthened to advance the practice of occupational health nursing. The occupational health nurse as the primary health care manager must take the lead in the development and implementation of a concept of health at the worksite. PMID- 2242168 TI - Health care records and the law. Balancing the employee's privacy with the state's regulatory power. PMID- 2242169 TI - Contact lenses in an industrial environment. PMID- 2242170 TI - Neurodevelopmental outcome of children with evidence of periventricular leukomalacia on late MRI. AB - Fifteen children, 8 months of age or older, from a neonatal follow-up program underwent magnetic resonance imaging and neurologic, cognitive, and language evaluations. Magnetic resonance imaging findings in all children included increased white matter signal on T2-weighted images and ventricular enlargement adjacent to regions of abnormal white matter. The extent of degree of abnormal white matter signal and the degree of sulcal prominence were variable. Twelve children had cerebral palsy; 5 children, 4 of whom had cerebral palsy, manifested significant sensory impairments. The median score on cognitive testing was 89; only 2 children exhibited severe-to-profound cognitive disability. Cognitive scores were stable on retesting. The degree of motor disability was correlated with the extent of white matter signal abnormality; however, cognitive outcome was not related to the extent and degree of white matter signal abnormality or to the degree of sulcal prominence. Despite the association of a major handicapping condition and periventricular leukomalacia, cognitive and language functioning may be relatively spared. PMID- 2242171 TI - Decrease in cerebral metabolic rate of glucose after high-dose methotrexate in childhood acute lymphocytic leukemia. AB - We measured changes in the regional cerebral metabolic rate of glucose (rCMRGlu) using 18F-fluorodeoxyglucose and positron emission tomography for the assessment of neurotoxicity in childhood acute lymphocytic leukemia treated with high-dose methotrexate (HD-MTX) therapy. We studied 8 children with acute lymphocytic leukemia (mean age: 9.6 years) treated with HD-MTX (200 mg/kg or 2,000 mg/M2) therapy. CMRGlu after HD-MTX therapy was most reduced (40%) in the patient who had central nervous system leukemia and was treated with the largest total doses of both intrathecal MTX (IT-MTX) and HD-MTX. CMRGlu in the whole brain after HD MTX therapy was reduced by an average of 21% (P less than 0.05). The reductions of CMRGlu in 8 patients were correlated with total doses of both IT-MTX (r = 0.717; P less than 0.05) and systemic HD-MTX (r = 0.784; P less than 0.05). CMRGlu of the cerebral cortex, especially the frontal and occipital cortex, was reduced more noticeably than that of the basal ganglia and white matter. We suggest that the measurement of changes in rCMRGlu after HD-MTX therapy is useful for detecting accumulated MTX neurotoxicity. PMID- 2242172 TI - Rett syndrome: cerebellar pathology. AB - The cerebellar pathology at autopsy of 5 patients with Rett syndrome is described. The patients ranged in age from 7-30 years. All had markedly reduced brain weights with proportionately small cerebella. Microscopic examination revealed loss of Purkinje cells, atrophy, astrocytic gliosis of the molecular and granular cell layers, and gliosis and loss of myelin in the white matter. Cortical atrophy occurred focally along the folia and was often more marked in the tips of the folia. The 2 oldest patients had been treated with phenytoin which may have contributed to the morphologic changes. Atrophy and gliosis increased with age or in patients without phenytoin treatment; the youngest patient demonstrated only minor microscopic changes. In addition to the generalized alterations, 1 patient had several adjacent folia with severe atrophy. The results indicate that cerebellar changes in Rett syndrome consist of general hypoplasia with the addition of atrophy beginning in childhood and progressing over many years. PMID- 2242173 TI - Recurrent lateral rectus palsy in childhood. AB - Five patients with recurrent, lateral rectus palsy in childhood, examined at the University of Iowa Hospitals over a period of 22 years, are reported. During the same period, 131 abducens nerve palsy patients, younger than 18 years of age, were evaluated. Eighteen similar patients, most single case reports, are reviewed from the literature. All reported patients, including our own, shared the following features: spontaneous recovery within 6 months in the majority of patients, ipsilateral recurrence, and painless palsy. There is female and left sided preponderance. Etiology is undetermined. Hypotheses include viral etiology, neurovascular compression by aberrant artery, and migraine. PMID- 2242174 TI - Transient neurologic abnormalities and BAEPs in high-risk infants. AB - We examined brainstem auditory evoked potentials in 2 neurodevelopmentally different groups of high-risk premature infants during the first year of life. Our 77 patients were considered at birth to be at risk for neurologic disabilities, but were found to have normal development in the second year of life. The patients were divided into 2 groups on the basis of their neurologic findings during the first year of life; 24 of the 77 patients demonstrated transient neurologic abnormalities (group I) and the remaining 53 demonstrated normal neurologic findings through the first year of life (group II). Normative data of brainstem auditory evoked potentials were obtained from 60 low-risk and neurologically normal infants. Group I patients had prolonged III-V and I-V intervals at 2 months of age or younger and poorly detectable waves VI and VII at 5 months of age or younger, compared with control subjects. Wave VI was poorly detected in group II patients only at 35-39 weeks of conceptional age. Brainstem auditory evoked potentials suggested that the patients with transient neurologic abnormalities had transient dysfunction or maturational delay in the brainstem and upper auditory pathway early in the first year of life. PMID- 2242175 TI - Ultrasonography and magnetic resonance imaging in Leigh disease. AB - An infant with Leigh disease, who was the younger sister of a similarly affected infant, had been examined before the onset of the disease. Ultrasonography revealed hyperechoic lesions in the putamen and caudate nucleus during the preclinical stage. At onset, these changes extended into the cerebral cortex and medulla. These lesions were also detected by T2-weighted magnetic resonance imaging (MRI) as areas of increased signal intensity. Her brother demonstrated the same ultrasonographic results; cranial computed tomography disclosed low density areas in the basal ganglia which were detected as hyperechoic lesions by ultrasonography. These findings suggest that ultrasonography is useful in detecting early intracranial lesions in Leigh disease. PMID- 2242176 TI - Subcortical visual function in the newborn. AB - Early behavioral visual function in infants may not depend upon the geniculocalcarine pathway but may be mediated through more primitive subcortical pathways. This subcortical visual system may exist in early life and be responsible for visual pursuit and perhaps fixation. In some infants with damage to the visual cortex, the subcortical pathway may persist beyond the neonatal period. Three infants with major defects in the visual cortex are reported. These infants displayed persistent preservation of visual pursuit movements without evidence of visual recognition. Limited behavioral expressions of vision in the infant with damage to the visual cortex may not always be an indicator of preserved function of the visual cortex. PMID- 2242178 TI - West syndrome associated with hyperlexia. AB - Two patients are reported with West syndrome associated with hyperlexia. They had peculiar linguistic and psychosocial development and autistic behavior, yet began to read Japanese and Chinese characters, numbers, Roman alphabet letters, and trademark letters at 3 years of age. Neuropsychologic, electroencephalographic, and radiologic studies were performed at 11 years of age in Patient 1 and at 10 years of age in Patient 2. Although they were able to read fluently with correct intonation, their comprehension was significantly impaired. The neuropsychologic evaluation of both patients demonstrated selective, excellent ability in auditory memory in contrast to impairment of associational abilities, visual retention, and visual constructional abilities. These findings suggest that the functions in the nondominant hemisphere were also impaired. Although children with West syndrome frequently have associated mental retardation, patients with West syndrome associated with hyperlexia have never been reported. A neuropsychologic investigation of epileptic children with mental retardation is necessary for the detection of hyperlexia. PMID- 2242177 TI - Rett syndrome: findings suggesting axonopathy and mitochondrial abnormalities. AB - We report the histopathologic findings of 3 sural nerve biopsies and 1 muscle biopsy from 3 patients with Rett syndrome. The 3 sural nerve biopsies demonstrated a few ultrastructural abnormalities, including the presence of many Pi-granules and mitochondrial changes in the cytoplasm of Schwann cells, occasional bands of Bungner and onion-bulb formations, and mitochondrial alterations in myelinated axons. Morphometric analysis disclosed reduction in the number of large myelinated fibers with normal densities in comparison to those of an age-matched normal control. Light microscopic examination of the biopsied muscle from a 6-year-old patient with Rett syndrome revealed the existence of many small, dark, angulated fibers with NADH-TR staining. Ultrastructural investigation of the muscle confirmed the presence of the dumbbell-shaped mitochondria. Peripheral nerve involvement and the possibility of mitochondrial abnormalities in Rett syndrome were suggested by the results. PMID- 2242179 TI - [Site and incidence of multiple cancers in patients with squamous cell carcinomas of the upper aerodigestive tract]. AB - The etiology of multiple primary cancers has not been clearly elucidated, although some pathogenic factors are known. The studies reported here include 796 patients who, between January 1970 and March 1989, presented with a carcinoma of the upper aerodigestive system. The charts of 687 patients were analyzed retrospectively; 109 patients were studied prospectively by systematic pretherapeutic panendoscopy. Multiple primary cancers were found in 76 cases (9.5%), 33 patients had synchronous cancers, and 43 had metachronous cancers. In the prospective study, the incidence of multiple cancers was higher (13.7%) than in the retrospective group (8.8%). Synchronous primaries were more frequent in the prospective study (8.2%) than in the retrospective analysis (3.4%). Second primaries were mostly found in the esophagus, the hypopharynx, the buccal cavity, and the lung. The authors also examined whether the anatomic location of the second primary cancer can be related to the site of the first. The five-year survival rate among patients with synchronous cancers (18%) was lower than among patients with metachronous cancers (41%). The prognosis for synchronous cancers deteriorates if the planned treatment has to be modified following the discovery of a second primary. Systematic pretherapeutic panendoscopy should be used to help detect early asymptomatic second primaries which might be missed during clinical examination. PMID- 2242180 TI - [Incidence of epithelial neoplasms in the head and neck area in non-Hodgkin's lymphomas]. AB - There is an increased risk of malignancy in patients with genetically determined or acquired immunosuppression. The authors report a case of a 70-year-old patient with a lymphoplasmocytic immunocytoma who developed 19 squamous-cell carcinomas (SCC) and nine basal-cell carcinomas (BCC) over a three-year period. This was the reason to review 100 cases of malignant lymphomas for evidence of additional malignancies. Of these patients, 15% had one or more SCC or BCC in the head and neck area. The age range was 59 to 79 years (mean, 71.7 years) and the male:female ratio 11:4. One or more SCC arose in 93% of these patients, 36% developed an additional one or more BCC, and BCC alone occurred in 7%. The usual ratio of BCC:SCC is 10:1; in the authors' patients, by contrast, this ratio was 6:14. In 12 cases, SCC and BCC were located on the skin. The remaining cases of SCC developed in the oral mucosa, the tonsils and the hypopharynx. In 13 cases, low-grade malignant lymphomas were found and in two cases high-grade malignant lymphomas were found. The SCC were clinically aggressive. Thirty-six percent of the patients had recurrent lesions, 43% multiple neoplasms, and 50% metastases. Histologically, the SCC showed moderate to poor differentiation, a high degree of cell polymorphism and mitotic activity, and deep tissue infiltration. There are several explanations for the increased incidence of neoplasms in patients with immunodeficiency disorders. The surveillance function of the immune system may be impaired due to the disease itself or due to the treatment for immunosuppression. Immunosuppressive and cytotoxic agents are potential carcinogens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242181 TI - [Imaging diagnosis of parotid diseases--a comparison of methods]. AB - Thirty-five patients with parotid gland disorders were ultrasonographically examined with a "small parts" scanner, as well as with high-resolution computed tomography, and conventional and digital subtracted sialography. The results were compared with clinical, surgical, and pathomorphological data. In cases of parotid gland masses, the sensitivity of sonography, CT, and sialography was 100%, 81%, and 70% respectively, while in cases of sialadenitis, sensitivity was 38%, 50%, and 75%. The image-quality of digital subtracted sialography was superior to conventional sialography in 94% of cases, the same in 6%, and inferior in none of the cases. It is concluded that in all cases of parotid gland diseases ultrasound should be the first imaging method. If a tumor is confirmed, no further pretherapeutic imaging will be necessary in most cases. If a tumor is not confirmed, digital subtracted sialography should be employed to visualize inflammatory changes. PMID- 2242182 TI - [Extracorporeal piezoelectric lithotripsy in the treatment of a parotid calculus with recurrent parotitis]. PMID- 2242183 TI - [Acute purulent parotitis as a sequela of alkylphosphate (E 605) poisoning]. AB - Acute suppurative parotitis is a possible consequence of poisoning by organophosphates (E 605). The endogenous accumulation of acetylcholine results- as in the acute pancreatitis caused by poisoning with organophosphates--in massive hyperemia and an increased secretory activity with leakage of saliva into the tissue, in an activation of the kallikrein-kinin system, the phospholipase A2, and, ultimately, in toxic tissue lesions caused by lysolecithin and the superoxide-radical anion. In spite of antibiotic therapy this is followed by bacterial inflammation. Treatment consists in the administration of aprotinin (Trasylol) and corticosteroids. In the case of abscess formation surgical drainage is necessary. PMID- 2242184 TI - [The accuracy of subjective determination of auditory threshold in the range of 0.5 to 18.0 kHz using different sound transducer systems]. AB - This paper reports on the degree of accuracy of determinations of hearing threshold in the 0.5 to 18 kHz range. As far as possible, these hearing thresholds were compared with those of ISO 389. Furthermore, the study compared determinations of hearing thresholds measured on different days. Reproducibility was very good, particularly of the high-frequency thresholds. The two types of sound transducers used here (a quasi-free field system developed by the authors and a pair of professional headphones) showed an identical transmission of frequencies and good reproducibility of the results of measurements. PMID- 2242185 TI - [Relations between the summation potential and frequency selectivity]. AB - In cases of inner ear diseases, e.g.m. Meniere, summation potential (SP) can be measured using the extratympanic elektrocochleographic method. This potential is a consequence of hydrops in the cochlea. In 128 patients with confirmed SP, it was also possible to measure frequency selectivity (FS) using the psychoacoustic method. Reduced FS was found to a greater or lesser degree in the basal and apical turn of the cochlea. It can be assumed that both phenomena are to be attributed to the same cause. PMID- 2242186 TI - [The latency behavior of early auditory evoked potentials in high frequency hearing loss]. AB - We evaluated the auditory evoked brainstem responses of 53 patients with unilateral or bilateral (79 ears) high-frequency hearing loss of cochlear origin, to see whether the reduction of I-V latency difference in high-frequency hearing loss that has been described by several authors, was present in our patients. We were able to confirm that in high-frequency hearing loss wave I-latency is significantly positively correlated with the degree of hearing loss. The I-V latency difference is significantly negatively correlated with the degree of hearing loss at 2000 Hz. PMID- 2242187 TI - [Computerized tomography findings in neck abscess ]. AB - Computed tomography was the diagnostic confirming method in two patients with a necrotic cervical phlegmon caused by an infection of streptococcus pyogenes and candida albicans. A cervical phlegmon is frequently caused by the lymphogenic transmission of diverse primary infections. The time between the primary infection and the appearance of a cervical phlegmon is very varied. In rare cases it is possible that the primary focus will have cured completely. The cervical fasciae separate the neck into three different spaces, which, together with their hypostatic abscess paths, can be visualized using CT. The use of the central veins (e.g., the jugular vein) to administer medication etc. means that the deep cervical phlegmone will continue to be a complication in intensive-care patients. PMID- 2242188 TI - [Modern imaging of the larynx]. AB - Many diseases of the larynx can be diagnosed by clinical examination. In many cases, however, further diagnostic procedures are necessary to receive adequate information on the localisation and extent of the lesion. In the present paper the authors report on the different possibilities of diagnostic imaging of the larynx. The value of each technique is discussed to set adequate indications as well as to recommend an appropriate imaging for laryngeal lesions. PMID- 2242189 TI - [Differential diagnosis of otorhinolaryngologic pain syndromes]. AB - As a guiding symptom, acute pain usually leads to the correct diagnosis. In most cases, chronic pain has lost its warning effect. It is often a diagnostic problem to localize the starting point of the pain. Thus, seeking the advice of a number of specialists has proved to be valuable. In more than half of the "pain patients", complaints of pain in the head and neck area are prevalent. The article deals with several pain syndromes which are of importance for the ENT physician. Pain in the ear can be caused by inflammation, tumor, or injury in the area of 5th, 7th, 9th, and 10th cranial nerves, and of the course of the cervical nerves 1-3. In facial pain, symptomatic reasons such as tumors along the involved nerves, Sjogren's, or styloid syndrome, have to be taken into consideration. PMID- 2242190 TI - [A short history of hearing research. II. Renaissance]. AB - The history of basic research on the function of the hearing organ is revisited. The present, second part of the review covers the period between the renaissance of anatomical research in the 16th century and the beginning of modern hearing research at the end of the 19th century. Andreas Vesalius gave the two ossicles malleus and incus their names. His scholar Philippus Ingrassia found 1546 the third ossicle, the stapes. The cochlea was discovered 1552 by Bartholomeus Eustachius and denoted as cochlea 1561 by Gabriel Falloppio. Thomas Willis speculated 1672 that different "tones" (species audibilis) may excite different fibres of the nervus acusticus. In collaboration with the physicist Edme Mariotte, Joseph Guichard DuVerney developed in 1683 a theory of the tonotopical organisation of the cochlea, the encoding of acoustic information by mechanical spectral analysis. The scholastic dogma of Aristotle's aer implantatus was contradicted by Domenico Cotugno as late as 1760. DuVerney's theory was, together with Georg Simon Ohm's law on the applicability of the Fourier analysis to sound waves, the basis of Hermann Helmholtz' famous theory of hearing of 1863. Due to the lack of detailed knowledge about the function of nerves, however, no clear ideas were developed about the acoustical information carried to the brain by the acoustic nerve. Also in the 19th century, Alphonso Corti discovered the organ that was named after him by Albert von Kolliker, and Flouren's experiments demonstrated the function of the vestibular organs. Furthermore, the foundations of auditory psychophysics were laid by Alfred M. Mayer and others. PMID- 2242191 TI - [Reconstruction of the rudimentary external ear]. PMID- 2242192 TI - Health maintenance organizations and medical education: breaking the barriers. AB - Academic medical centers (AMCs) are under pressure to increase ambulatory medical education, but their capacity for such teaching is limited. Health maintenance organizations (HMOs) are a large and growing institutional setting that could participate in clinical education. Until now, relatively few HMOs and AMCs have reached agreements about teaching, because traditional suspicions have blocked collaboration. Responding to a case prepared as the basis of discussion, about 450 academics and HMO medical directors explored the barriers to and incentives for cooperation between AMCs and HMOs in clinical education. The two groups identified different issues as barriers to collaboration, leaving considerable room to negotiate agreements. AMCs, especially, need to be prepared to offer meaningful academic and financial inducements to attract HMOs to participate in teaching. PMID- 2242193 TI - Feedback in an objective structured clinical examination by medical students serving as patients, examiners, and teachers. PMID- 2242194 TI - New thoughts about medical students as effective searchers of MEDLINE. PMID- 2242195 TI - Using a computerized database to manage a decentralized ambulatory care clerkship. PMID- 2242196 TI - Developing a computer-based system to document and report students' clinical patient encounters. PMID- 2242197 TI - Human values versus animal rights. PMID- 2242198 TI - AIDS: just another disease? PMID- 2242199 TI - A survey of medical school teachers to identify basic biomedical concepts medical students should understand. AB - Insights from the cognitive sciences indicate a continuing need for physicians to understand conceptual knowledge from the basic sciences, despite recent concerns regarding the increasing amount of information in medicine and the growing emphasis on performance skills. A 1987 survey of selected basic science and clinical teachers in North American medical schools was undertaken to identify basic biomedical concepts that are important in the practice of medicine and to specify how difficult these are for students to learn, apply, or both. Responses from faculty (nominated by their deans to answer the survey) from 82% of the medical schools indicated considerable agreement between the basic science teachers and clinical teachers on the relative importance of a set of biomedical concepts, and showed relatively minor levels of disagreement on how difficult these concepts are. The judgments of these teachers could prove extremely useful in (1) determining concepts that--because of their importance--should receive special attention in curriculum efforts, and (2) determining concepts that- because of their difficulty--need "special handling." PMID- 2242200 TI - Predictive validity of the American Board of Family Practice In-Training Examination. AB - Most research into the validity of graduate medical education in-training examinations has focused on construct validity and concurrent validity issues. This study examined the predictive validity of the American Board of Family Practice In-Training Examination using multivariate analysis of all U.S. family practice residents who took the certification examination in either 1987 or 1988. Results of these two certification examinations were analyzed for the cohorts of physicians who had taken in-training examinations as first-, second-, and third year residents. Multiple regression analysis showed that the composite score, and all but one part-score, of each in-training examination were independently predictive of performance on the certification examination. This study also found that the older residents did less well on the certification exam, and that men and women each did better on selected portions of the examination. The implications of these findings for in-training examinations in other specialties and for program directors and residents are discussed. PMID- 2242201 TI - Medical and dental students' attitudes about the AIDS epidemic. AB - This study investigated changes, over a one-year period, in medical and dental students' attitudes toward various issues related to contact with AIDS patients. In 1988 and 1989, the authors surveyed second- and third-year medical and dental students at one medical school both before and after they completed a year of required clinical training. The dental students remained consistently more anxious and more restrictive in their attitudes toward treating patients with AIDS than did their medical student counterparts, and became more conservative (fearful) in their attitudes after working with AIDS patients, whereas the medical students became more liberal. Overall, both groups were more concerned about contracting AIDS in their professional lives than in their personal lives. Over one-third of the medical students and two-thirds of the dental students indicated that they did not wish to train in a specialty or hospital with a high percentage of AIDS patients, and a substantial minority of the students in both groups did not feel that they were responsible for treating all patients whom they were qualified to treat. These and related results suggest that AIDS-related anxiety may influence students' career choices and behaviors and the quality of care patients receive. Suggestions for educational strategies to address students' fears--both warranted and unwarranted--and the differences in attitudes between students of different health-care professions are discussed. PMID- 2242202 TI - The impact of an AIDS symposium on attitudes of providers of pediatric health care. AB - Following reports of concern among health-care workers regarding the occupational risk of infection with the human immunodeficiency virus (HIV), a symposium was designed in 1987 to demonstrate to health-care providers at three hospitals in The Bronx, New York, the low risk of occupational HIV infection and techniques for avoiding infection. After the symposium, 103 of the health-care providers who had attended it completed a questionnaire assessing the impact of the symposium on their attitudes; the responses from 100 of these providers were used in this study. Twenty-nine of the responding providers reported that the symposium had increased their concerns regarding their risk of HIV infection; this group was composed of seven of the 15 medical students who responded, 12 of the 36 housestaff, seven of the 28 faculty, and three of the 21 other medical staff. The findings of the present study suggest that a symposium designed to decrease concerns of occupational HIV infection among health-care workers may have the opposite effect on some of those who attend it, especially medical students. Education alone may be inadequate to reassure some providers. The authors recommend small-group sessions addressing the emotional aspects of health-care providers' concerns. PMID- 2242204 TI - Medical and nursing students' attitudes about AIDS issues. AB - A 12-item questionnaire was administered in late 1987-early 1988 to 445 medical students, 133 medical school applicants, and 111 nursing students to assess any differences in their attitudes toward medicine-related AIDS issues. These groups were also given a 31-item test of their knowledge of AIDS issues. Significant differences by levels of knowledge were obtained for eight of the 12 attitude items. For example, the more knowledgeable the student, the less likely he or she was to refuse treatment to an AIDS patient, to require mandatory AIDS testing of physicians, or to require medical personnel to wear gloves. The findings strongly suggest that education has an important role in changing attitudes about AIDS in a direction that fosters better health care for AIDS patients. PMID- 2242203 TI - Attitudes of medical school faculty and students toward acquired immunodeficiency syndrome. AB - Attitudes of faculty and students will influence the success of educational programs to address acquired immunodeficiency syndrome (AIDS). In 1988-89, 170 medical school faculty and 227 students completed needs assessment questionnaires at the University of Louisville, and the results were compared to assess the respondents' attitudes about AIDS. Both the faculty and the students were found to be fearful of infection, had strong negative attitudes toward AIDS patients, and had low levels of confidence in the current knowledge about AIDS. Both cognitive and affective training strategies are recommended to help learners distinguish unwarranted from warranted fears of infection and to increase their empathy for patients with AIDS. PMID- 2242205 TI - Predictors of medical and nursing students' levels of HIV-AIDS knowledge and their resistance to working with AIDS patients. AB - Among health professionals, knowledge about the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) is often limited, inaccurate, or both. Many health professionals also resist working with AIDS patients. This 1988 survey examined exaggerated risk estimates for HIV contagion in relationship to HIV-AIDS knowledge and resistance to working with AIDS patients among medical and nursing students at a large Northwestern teaching hospital. The results indicate that among the respondents, exaggerated risk estimates were associated both with a lack of HIV-AIDS knowledge and with greater resistance to working with AIDS patients. Results from multiple regression analyses revealed that (1) a lack of clinical experience with AIDS patients and (2) antihomosexual attitudes were significantly associated with the students' lack of HIV-AIDS knowledge, even after controlling for the effects of exaggerated risk estimates. The first two variables also were shown to be significantly predictive of the students' resistance to working with AIDS patients, as was an intolerance of drug use and drug users, beyond the influence of exaggerated risk estimates. Specific approaches of developing effective HIV-AIDS educational programs for health professionals are proposed. PMID- 2242206 TI - Willingness of health-professions students to treat patients with AIDS. AB - This 1988-89 survey of 319 students in the medical, dental, nursing, and allied health-care professions revealed that over one-third had some reservations about treating acquired immunodeficiency syndrome (AIDS) patients. Most were unwilling to perform mouth-to-mouth resuscitation on patients with AIDS, and most also believed that health-care workers had the right to refuse care to AIDS patients. Unwillingness to treat AIDS patients was strongly associated with homophobic attitudes and concerns that patients with AIDS posed a risk to health professionals. AIDS education for health professionals should emphasize methods for the prevention of HIV infection among health workers, and include teaching strategies designed to deal with the irrational feelings that AIDS often engenders. PMID- 2242207 TI - Analysis of residents' performances on the In-Training Examination of the American Board of Anesthesiology-American Society of Anesthesiologists. AB - An analysis of the results of the In-Training Examination of the American Board of Anesthesiology-American Society of Anesthesiologists has been developed using a new question-categorization method and a new form of calculation, the resident index score. Resident index scores permit comparison of the performance of any program's residents with the performance of all U.S. residents who took the examination. This study analyzed examination results from eight residency programs for a five-year period, 1983-1987. Statistically significant differences in the residents' performances were found both within and among the residency programs during this time. Areas of educational strength and weakness were identified by levels of training for each program. The analyses of the individual programs' results were provided to the respective program directors on a confidential basis, and have been used to change curriculum content, modify lectures for residents, and provide structured review for residents. Similar analyses can be provided as a service to other residency program directors. PMID- 2242208 TI - Minority students' career choices and education five years after they completed a summer enrichment program. AB - The purpose of this follow-up study was to ascertain the career selections and college majors of 101 students from minority groups who had attended a summer enrichment program at the Medical College of Georgia (MCG) in Augusta from 1979 to 1983, to determine whether the program had been successful influencing the students to choose a health-related career. All the students had completed high school within the previous five years; they were contacted by mailed questionnaires or telephone. The study was completed by contacting the colleges where the students had enrolled and through the use of the Student and Applicant Information System of the Association of American Medical Colleges. The findings showed that the students had enrolled in and graduated from college and that a significant number of the students had chosen medicine or another health-related career. The study suggests the importance of early academic intervention for students from minority groups to choose a medical career. PMID- 2242209 TI - The relationship of minority students' MCAT scores and grade point averages to their acceptance into medical school. AB - The authors identified relationships between quantitative academic variables- specifically, grade-point averages (GPAs) and Medical College Admission Test (MCAT) scores--and the admission decisions of 58 students from minority groups underrepresented in medicine. These students had participated in a summer enrichment program at the University of Virginia School of Medicine and had applied to medical school. A total of 49 of the students were offered admission, and ultimately enrolled in 17 different medical schools. Results of a stepwise multiple regression analysis indicated that scores on the Skills Analysis: Quantitative Subtest of the MCAT explained the greatest percentage of the variance related to medical school admission (26%); scores on the Skills Analysis: Reading Subtest contributed an additional 7% to the explained variance, and scores on the Physics Knowledge Subtest, another 5%. The overall GPAs did not contribute significantly to the explanation of the variance in admission decisions. These results differ from published findings based on data from minorities' admissions to individual institutions. Caution must therefore be exercised when using GPAs and MCATs as medical school admission predictors for students from minority groups. PMID- 2242211 TI - Assessing patients' satisfaction with care provided by residents in an academic HMO setting. PMID- 2242210 TI - Medical students' views of how the HIV-AIDS epidemic affects their education and choice of training programs. PMID- 2242212 TI - An interview technique to complement traditional criteria used in selecting internal medicine housestaff. PMID- 2242213 TI - Differences in teaching skills and attitudes among residents after their formal instruction in teaching skills. PMID- 2242214 TI - Evaluation of a case-oriented curriculum for an introduction to clinical medical course. PMID- 2242215 TI - Graduating medical students' debt and specialty choices. PMID- 2242216 TI - Guidelines for dealing with faculty conflicts of commitment and conflicts of interest in research. July 1990. Association of American Medical Colleges Ad Hoc Committee on Misconduct and Conflict of Interest in Research. PMID- 2242217 TI - The role of frontal neurons in pain and acupuncture analgesia. AB - To study the role of frontal neurons in pain and acupuncture analgesia, experiments were carried out on 4 monkeys (Macaca mulatta) during performing two tasks, the Heat Discrimination Response GO/NO-GO Task (Task I) and the Heat Delayed Discrimination GO/NO-GO Task (Task II). After a criterion of 90% of correct performances over three successive days had been reached, activity of single neurons was recorded from the frontal cortex. Of 276 Task I-related neurons, 211 responded to noxious and/or innocuous heat stimuli. Of 73 Task II related neurons, 59 responded to noxious and/or innocuous heat stimuli. During acupuncture, the nociceptive reaction time for lever release to avoid painful stimuli was increased, the percentage of correct performances was lowered, and the neuronal responses to noxious and/or innocuous stimuli were suppressed. These neurons were mainly located in a circumscribed area medial to the superior ramus of the arcuate sulcus in frontal cortex, including the prefrontal and premotor areas. It is suggested that neurons in this area may be related to the discrimination of noxious and innocuous stimuli. The suppression of the activity of these neurons during acupuncture may be involved in the whole mechanism of acupuncture to facilitate the production of analgesia. PMID- 2242218 TI - Synaptic inputs from rods and cones to horizontal cells in the tiger salamander retina. AB - Synaptic inputs from rods and cones to horizontal cells (HCs) were studied in the flatmounted isolated retinas of the tiger salamander. Voltage-intensity relations, spectral sensitivities and response waveforms of the rod, the cone, and the HC under dark- and light-adapted conditions were examined. HCs receive mixed inputs from rods and cones in both dark- and light-adapted retinas. The relative rod/cone input in HCs depends on the intensity of stimulus and background illumination, and it varies from HC to HC. PMID- 2242219 TI - Spectra properties of rat liver mitochondrial choline dehydrogenase. AB - Choline dehydrogenase contains the prosthetic group FAD, non-haem iron and acid labile sulfur. However, the absorption spectra of the purified enzyme do not change after adding substrate. The reduced absorption spectra of choline dehydrogenase can only be determined after the addition of dithionite. Those choline dehydrogenases situated in the mitochondrial inner membrane can be reduced by substrate and exist in the reduced state. When cholate was used to solubilize the substrate-reduced choline dehydrogenase, the reduced spectra will gradually disappear. However, if solubilization is carried out under anaerobic conditions, the reduced spectra can be retained, suggesting that the solubilized choline dehydrogenase can use oxygen as an acceptor. PMID- 2242220 TI - Preliminary crystallographic analysis of deshexapeptide (B25-B30) insulin. AB - Satisfactory single crystals of deshexapeptide (B25-B30) insulin for X-ray crystal structure analysis have been grown in citrate buffer by the method of hanging-drop gas phase diffusion. The crystal belongs to the monoclinic system with space group C2. The unit cell constants are a = 42.6 A, b = 37.9 A, c = 27.2 A, beta = 125.4 degrees and there is only one molecule of deshexapeptide insulin in an asymmetric unit. PMID- 2242221 TI - Effects of deoxycorticosterone acetate on muscle electrolytes, resting potential and mitochondria in rats. AB - Deoxycorticosterone acetate, injected daily for 5, 10, 20 or 30 days, reduced the serum potassium levels of rats by about 25%, a decrease that was independent of the treatment period employed. Serum sodium concentrations were unchanged with treatment duration. The potassium concentrations in extensor digitorum longus (EDL) and soleus (SOL) muscles were significantly decreased, and those of sodium increased, after treatment. Accompanying these changes of electrolyte concentration, the resting membrane potentials of treated EDL and SOL were hyperpolarized in vivo, and showed depolarization with the decreases of external potassium concentrations in vitro. The mitochondria in the muscles of treated rats were damaged. The degree of damage was more serious in EDL than in SOL and was dependent on the duration of deoxycorticosterone acetate treatment. PMID- 2242222 TI - Presidential address 1990--coming in from the cold. PMID- 2242223 TI - Soothing techniques used in barium enema examinations. AB - This article is part of a research project being carried out to explore and develop stress reduction methods which can be used in x-ray departments. It describes the results of a survey which shows that a high proportion (90%) of those involved in barium examinations agree there is a relationship between the anxiety of the patient and the difficulty of the examination. Many of those involved in the examination (87%) report using methods which they think are effective in reducing patients' anxiety. There is little difference between the opinions of the various professional groups involved in barium enema examinations. From this research a list has been developed of the anxiety reduction techniques presently employed during barium enema examinations. The article endorses the need for further study of methods for reducing patients' anxiety during x-ray examinations. PMID- 2242224 TI - Ultrasound of the acute abdomen--Part IV. PMID- 2242225 TI - Bone density scanning for osteoporosis. PMID- 2242226 TI - Wrist arthrography. PMID- 2242227 TI - The DCR psychology course at Stoke. AB - This article describes the course developed at Stoke-on-Trent to cover the psychological aspect of patient care, inter-staff relationships and communication skills. Emphasis is placed on the recent developments in the content of course against a background of the continuing use of experimental learning methods. The importance of clinical experience is stressed together with the notion that students gain confidence in their own abilities by practising in a safe environment. The article is presented for the consideration of teachers engaged in this essential part of the syllabus and curriculum. PMID- 2242228 TI - Mitral valvuloplasty revisited. PMID- 2242229 TI - Emotionally and practically supporting those attending a radiotherapy department and radiographers working with them. PMID- 2242230 TI - The radiographer and the well-woman. PMID- 2242231 TI - Ultrasound of the acute abdomen--Part V. AB - Patients with an acute abdomen have complaints of brief duration which must be properly diagnosed and treated to reduce mortality and morbidity. There are a few instances, mostly involving massive haemorrhage, where the patient's condition is so poor that minutes count and a delay in operation will result in fatality. Imaging techniques have no role in these circumstances. In the majority of cases, however, there is time to make use of the various diagnostic imaging methods available to help arrive at the correct diagnosis. The role of ultrasound in this setting has been reviewed. Our own experience supports the view that it is an important modality for the investigation of patients with acute abdomen. It should be available on a round-the-clock basis. PMID- 2242232 TI - Multisite pressure ulcer prevalence survey. AB - The prevalence of pressure ulcers was 9.2% in the 148 hospitals included in the survey. Fifty-eight percent of ulcers were found in patients between the ages of 70 and 89 years. The sacrum was the most common site of ulcers (38%), but the trochanter had the most Stage IV ulcers. Patients had an average of 1.7 ulcers, and Stage IV ulcers were more common in African-Americans and in hospitals over 500 beds. The most commonly used support system was a purchased overlay, but 20 percent of the patients with ulcers were lying on traditional hospital mattresses. PMID- 2242233 TI - Preventing pressure ulcers in institutionalized elders: assessing the effects of small, unscheduled shifts in body position. AB - This pre-test/post-test, two-week experimental clinical study compared the effect of small, unscheduled shifts in body position in preventing pressure ulcers in two groups of elders (n = 19) determined at risk by the Norton Scale. No statistically significant effects were found using these small shifts. PMID- 2242234 TI - Pressure relief characteristics of an alternating pressure system. AB - The pressure relieving characteristics of an alternating pressure mattress are compared to the characteristics of a traditional hospital mattress. The trochanteric pressures of 20 healthy volunteers had a mean of 95 (SD = 49) on a hospital mattress while the trochanteric pressures on the alternating pressure mattress had a mean of 67 (SD = 9) for the inflated cells and a mean of 23 (SD = 7) for the deflated cells. Statistical analysis revealed significantly lower interface pressure for the alternating pressure mattress. PMID- 2242235 TI - Stage I in ebony complexion. PMID- 2242236 TI - Personality, social support, and psychological distress in later life. AB - A conceptual model was developed to address 2 issues that have received relatively little attention in the social support literature. First, an attempt was made to assess the interrelationships among 3 types or dimensions of supportive social relations. In addition, the impact of selected psychological and social factors on social support use was examined. Findings from a nationwide survey of older adults in the United Kingdom suggest that social contact tends to increase the amount of received support, and received support in turn tends to bolster perceptions of support availability in the future (i.e., anticipated support). With regard to the second issue, social roles (especially marital status) and social extraversion emerged as potentially important correlates of social support use in later life. PMID- 2242237 TI - Social control, health risk taking, and psychological distress among the elderly. AB - Most research on older adults' social networks has focused on the support providing function of social relationships. Little gerontological research has addressed social control, or the role of social bonds in regulating deviant or risky behavior. Drawing on sociological theory, this study examined the hypothesis that social control discourages risky health practices while provoking psychological distress. Structured interviews conducted with 162 community residing older adults assessed social control (direct attempts by other to influence participants' health practices and the existence of significant role obligations to others), health risk taking (medication misuse, alcohol consumption, cigarette smoking, and the overall level of unsound health practices), psychological functioning (depression, loneliness, and self-esteem), and interpersonal satisfaction (satisfaction with friends and family members). Analyses revealed little support for the hypothesis. Social control was only weakly related to participants' health practices and, contrary to expectation, was generally related to less psychological distress and to greater interpersonal satisfaction. Implications for social control theory and for further research are addressed. PMID- 2242238 TI - Choosing social partners: how old age and anticipated endings make people more selective. AB - Carstensen's selectivity theory, which explains age-related change in social behavior in terms of emotion conservation and increasing discrimination among social partners, was investigated in 2 studies. In Study 1, 80 people aged 14 to 95 classified descriptions of people according to their similarities as social partners in terms of affect anticipated in the interaction and that this dimension was most important to older people. Study 2 showed how anticipated social endings influence partner selection: 380 people aged 11 to 92 chose familiar or novel partners under unspecified and ending conditions. Overall, older people chose familiar partners most frequently; yet when social endings were salient, younger people patterned the preferences of the elderly. These results suggest that social partner selectivity functions to conserve emotion resources in the face of limited future opportunities. PMID- 2242239 TI - Age differences in the enjoyment of incongruity-resolution and nonsense humor during adulthood. AB - This study tested a model of the development of incongruity-resolution and nonsense humor during adulthood. Subjects were 4,292 14- to 66-year-old Germans. Twenty jokes and cartoons representing structure-based humor categories of incongruity resolution and nonsense were rated for funniness and aversiveness. Humor structure preferences were also assessed with a direct comparison task. The results generally confirmed the hypotheses. Incongruity-resolution humor increased in funniness and nonsense humor decreased in funniness among progressively older subjects after the late teens. Aversiveness of both forms of humor generally decreased over the ages sampled. Age differences in humor appreciation were strongly correlated with age differences in conservatism. An especially strong parallel was found between age differences in appreciation of incongruity-resolution humor and age differences in conservatism. PMID- 2242240 TI - Ability correlates of memory performance in adulthood and aging. AB - The predictive relationships between an array of cognitive process and intellectual ability variables and text- and word-recall performance were examined. A sample of 584 men and women from 3 age groups (19-36, 55-69, and 70 86 years) completed a battery of 23 tasks marking 2 latent criterion variables and 10 latent predictor variables. The results indicated that (a) individual differences in process and ability variables predict performance on text and word recall, accounting for approximately half of the variance; (b) the pattern of predictors is quite similar for text and word recall; (c) age-related differences in text and word recall can be substantially accounted for by individual differences in constituent abilities, particularly indicators of verbal speed and working memory; and (d) there is some evidence to suggest that the pattern of ability-performance relationships varies across age, but such interactions appear to be relatively small. PMID- 2242241 TI - Application of social skills training in a group of institutionalized aggressive elderly subjects. AB - A social skills training program consisting of instructions, modeling, role playing, and feedback was carried out with a group of 6 verbally aggressive institutionalized elderly patients. Dependent measures included confirmed incidents of verbal aggressive behavior monitored across an ABAB design with a 5 month follow-up period. Results indicated that verbally aggressive behavior can be significantly decreased in a group-training setting and subsequently generalized to ward and other socialized behavior. Ancillary aspects of the study include the role of social reinforcement, participant modeling, and staff attitude, perception, and motivation. Implications for future research are discussed. PMID- 2242242 TI - Effects of aging on source monitoring: differences in susceptibility to false fame. AB - Older adults were less likely than young adults to spontaneously recollect the source of familiarity for previously read nonfamous names. Older adults were more likely to call old nonfamous names famous when subsequently encountered in a fame judgment task. Poor source monitoring by the elderly could not be accounted for by inability to recognize earlier read nonfamous names when specifically asked to do so. Both source-monitoring errors and recognition memory performance were based on attributions made about the experience of familiarity. Elderly subjects most prone to making familiarity errors recalled fewer items on a verbal learning task and were less likely to chunk information into semantic categories as it was recalled. This finding suggests that a decline in the tendency to spontaneously organize and integrate information underlies the poor source monitoring observed. PMID- 2242243 TI - Memory Functioning Questionnaire: concurrent validity with memory performance and self-reported memory failures. AB - Concurrent validity of factor scores from the Memory Functioning Questionnaire (MFQ; Gilewski, Zelinski, & Schaie, in press) with memory performance was investigated in 2 studies. Study 1 involved 198 adults aged 55-85; Study 2, 89 adults aged 50-87. After effects of depression, education, and health were partialed out, MFQ scores predicted performance on laboratory memory tests in Study 1 and performance on clinical memory tests and diaries of memory failures over 2 weeks in Study 2. Additional variance in predicting performance and failures recorded in diaries is accounted for by MFQ scores after partialing out subjects' responses to a yes-no question about whether they have memory problems. Results suggest that the MFQ has moderate concurrent validity with memory measures and is preferable to responses to a single question about memory self perception in assessing memory complaints in normal adults. PMID- 2242244 TI - Using personal and fictional documents to assess psychosocial development: a case study of Vera Brittain's generativity. AB - Adult diaries and novels written by the British feminist and pacifist Vera Brittain (1893-1970) were content analyzed for Eriksonian themes of identity, intimacy, and generativity. Brittain's concerns with identity and intimacy decreased over time, while her generative concerns increased, suggesting that she expressed the issue of generativity vs. stagnation in her mid-life diaries and fiction. The large number of identity themes relative to both intimacy and generativity provokes speculations about Brittain's personality, the characteristics of writers, the influence of gender, the impact of society, and the possibility that the crisis of identity vs. role confusion involves the last major structural change in personality development. This archival case study is consistent with Erikson's notion of a sequence of concerns with psychosocial issues, although directions for theoretical revision and elaboration are discussed. PMID- 2242246 TI - Effects of increased processing demands on age differences in working memory. AB - Three studies investigated (a) the plausibility of the claim that increasing the processing demands in a memory task contributes to greater involvement of a central processor and (b) the effects of altering reliance on the central processor on the magnitude of age-related differences in working-memory tasks. In the first study, young adults performed versions of 2 tasks presumed to vary in the degree of reliance on the central processor. In the second and third studies, young and older adults performed versions of a computation-span task that were assumed to vary along a rough continuum of the amount of required processing. The results indicated that although a central processor appears to be involved when working-memory tasks require simultaneous storage and processing of information, age-related differences in working memory seem to be determined at least as much by differences in the capacity of storage as by differences in the efficiency of processing. PMID- 2242245 TI - Psychological distress and somatic symptoms after natural disaster: differential vulnerability among older adults. AB - In a panel study, more than 200 older adults were interviewed before and after a severe flood in southeastern Kentucky in 1984. The issue in this study was whether older adult flood victims were differentially vulnerable to increases in psychological and physical symptoms on the basis of their age, sex, marital status, occupational status, education level, and preflood symptom levels. Flood exposure was related to increases in depressive, anxiety, and somatic symptoms at 18 months postflood. Within this older adult sample, men, those with lower occupational status, and persons aged 55-64 were at significantly greater risk for increases in psychological symptoms. Sociodemographic status did not moderate the impact of flood exposure on physical health. Implications for crisis intervention services to older adult disaster victims are discussed. PMID- 2242247 TI - Social support, life events, and stress as modifiers of adjustment to bereavement by older adults. AB - As part of a larger panel study, interviews were obtained from 3 samples of older adults: 45 persons who had recently lost a spouse, 40 who had lost a parent or child, and 45 who were not bereaved. Assessments were conducted before and after the deaths. In the widowed sample, health remained quite stable, but depression increased sharply, then remained elevated. Changes were minimal in the sample who had lost a parent or child and in the nonbereaved sample. Multiple regression procedures were used to identify factors that contribute to depression and health 9 months after the spouse's death. Postbereavement depression was associated with higher prebereavement depression, higher financial pressures, higher global stress, fewer new interests, and lower social support. Health was a function of prebereavement health, new interests, financial pressures, and global stress. In general, life events and resources had stronger effects in the widowed sample than in the comparison samples. PMID- 2242248 TI - Structural equation models of relationships between exercise and cognitive abilities. AB - Data were obtained from 300 men and women aged 55 to 91. Separate structural equation models of relationships between physical exercise and 3 cognitive performance variables--reaction time, working memory, and reasoning--fit the data well. Other variables in the models were age, health, education, and morale. Age and exercise affected each performance variable directly; education had a direct effect on reasoning only. There were also indirect effects of age and health on performance variables, mediated through exercise. The main hypothesis of the study, that exercise contributes to performance, was supported. A large decrease in model fit resulted when the path from exercise to each performance variable was deleted. Hypotheses that age-related deficits are primarily accounted for by lack of exercise or by poor health were not supported. PMID- 2242249 TI - Goal instability and later life adjustment. AB - A series of analyses on the goal instability personality construct, as measured by the Goal Instability Scale (GIS), was conducted to establish the construct validity of goal instability as it relates to older adults. This construct was derived from Heinz Kohut's psychology of the self. The sample consisted of a total of 157 voluntary early retirees representing a cross section of worker types from a manufacturing industry. In the first analysis, a series of confirmatory factor analyses supported the hypothesis that the 10-item GIS measures a unitary construct. In the second analysis, GIS was found to be similar across age groups. These findings enhance the conceptual clarity of the goal instability construct and its relevance with regard to older adults. Goal instability may represent 1 negative aspect of a quest for self-continuity. PMID- 2242250 TI - Close friendships among senior adults. AB - The purpose of this research was to evaluate the relative contributions of personal, affective, and social exchange characteristics to satisfaction with the best friendship. Senior adults (N = 76) described and evaluated their best friendships in terms of positive and negative affect, equity, reciprocity of social support, and satisfaction. The individual's endorsement of communal and exchange orientations were included as personal characteristics. The study confirms that a communal orientation enhances satisfaction with a best friendship and that conflict and negativity detract from it. Social exchange characteristics were not related to friendship satisfaction. The need to reevaluate the role of social exchange in close relationships is discussed. PMID- 2242251 TI - Relationship of personal-social variables to belief in paternalism in parent caregiving situations. AB - Paternalism in family caregiving may jeopardize the older persons' autonomy; it needs to be better understood. Study objectives were to determine the relationship of belief in paternalism to personal-social characteristics and to determine the relative importance of these variables as predictors of belief in paternalism. Forty-six pairs of daughters (age 49.7) and mothers (age 77.7) were measured on belief in paternalism, dogmatism, attitude toward elders, affective feelings toward the other, and background and caregiving variables. Among both mothers and daughters, dogmatism and attitude toward elders were related to belief in paternalism; daughters' affective feelings was also related. Caregiving variables were unrelated, and demographic background was important only for daughters. Attitude toward elders was the strongest predictor. Results were interpreted in terms of a traditional family ideology. PMID- 2242252 TI - Cognitive complaints in elderly depressed and pseudodemented patients. AB - The cognitive complaints of 11 patients with depressive pseudodementia were compared with those of 22 patients with depression alone. Pseudodemented subjects were defined as depressed inpatients showing reversible cognitive impairment as measured by the Mini-Mental State Examination (MMSE); subjects with depression alone had no such impairment. For each group, cognitive complaints were highly correlated with depressive symptoms and were not related to MMSE scores. The pseudodemented group had significantly higher cognitive complaint scores, complaining more of difficulties with concentration and recent memory. Groups did not differ significantly in complaints of difficulties with remote memory. PMID- 2242253 TI - Nursing process: help or hindrance? AB - Many standard nursing texts effectively treat 'the nursing process' and 'nursing' as one and the same, yet there have been few attempts to critically analyse the concept and its implications. This paper seeks to do both. PMID- 2242254 TI - Individual rights vs institutional rights: nursing imperatives for the provision of aged care services. AB - This paper offers nurses a legal perspective on some of the major issues arising from the Federal Government's proposal to establish a standard form contract and a charter of residents' rights and obligations for elderly residents in hostels and nursing homes. In emphasising the significance of these proposals it suggests that nurses, individually or collectively, have the potential to make a significant contribution to the continuing user rights debate. The proposed charter and contract and the objectives sought to be achieved by this package are considered. While there are strong and persuasive arguments favouring the concept, it is suggested that as proposed the charter and contract would be largely unworkable and impractical. Progress of the consultation process between Government and other interested bodies and the effect of subsequent drafting changes is discussed. Finally, the manner in which members of the nursing profession with experience and expertise in the provision of aged care services may contribute to the ongoing user rights debate is addressed. PMID- 2242256 TI - Terminally ill patients' expectations of nurses. AB - This exploratory study was undertaken to discover what nursing behaviours terminally ill patients desire. To rank patients' attitudes and judgements a Q sort consisting of 70 cards was used. The statements covered three categories: physical and psycho-emotional care of patients and psycho-emotional care of significant other/s. "I would like the nurse to help me remain at home for as long as possible" was the most favoured statement and the least favoured was: "I would like the nurse to talk to me about death and dying." The overall theme was that responsive rather than directive nursing behaviours were desired. Analysis identified five Factors from which a model of responsive nursing care was developed. Interpretation of the Factors indicated patients desired responsive nursing care that enabled them and their families to bring their own resources to the dying process, rather than having imposed upon them care which nurses deemed appropriate. PMID- 2242255 TI - AIDS: attitudes and education. AB - The purpose of this study was to explore hospital employed health professionals' attitudes to AIDS and homosexuals. Questionnaires were distributed to all health professionals in a 250-bed paediatric teaching hospital in Perth, Western Australia. The results constitute a database for nurses involved in staff development and AIDS education. The findings indicate that such programs must deal with the personal domain of attitudes to AIDS and homosexuals as much as with factual information. Furthermore, meaningful differences between target groups must be accommodated within the design of the program. PMID- 2242257 TI - Physical assessment of people with AIDS. AB - Since the Declaration of Alma-Ata in 1978, primary health care (PHC) has been acknowledged as the most effective means of achieving "health for all". Promotion of the PHC model provides nurses with an excellent opportunity for professional growth and development. The PHC role of nurse practitioner is gradually emerging within the Australian health care system and if nurses are to fulfil this role adequately they need to equip themselves with additional skills. The art of performing competent physical assessment of clients is one such skill. As the concept of the AIDS nurse practitioner is being developed locally and overseas, this paper focuses on the physical assessment of people with AIDS. While the constellation of physical signs and symptoms they experience are all too familiar to those who work in the area, they are often unusual for those who do not. PMID- 2242258 TI - Continuing education in physical assessment: a pilot study. AB - This study examines the effectiveness of a five day educational program designed to teach registered nurses (RNs) comprehensive physical assessment techniques and associated skills. Tests and questionnaires measured nurses' knowledge and use of physical assessment skills before and three months after its completion. It was found that the group had increased its physical assessment knowledge and the majority were using the learned skills. PMID- 2242259 TI - Leiomyosarcoma of the sinonasal tract. A clinicopathologic study of nine cases. AB - The clinicopathologic features of nine cases of sinonasal tract leiomyosarcoma (SNTL) referred to the Armed Forces Institute of Pathology, Washington, DC, during the period from 1970 through 1988 are described. This report represents the largest study to date on SNTL, and our results are compared with the 21 previously reported cases of SNTL. Of the nine cases described, patients ranged in age from 22 to 86 years (mean, 55 years). The most frequent clinical presentation was nasal obstruction unilaterally. The neoplasms were limited solely to the nasal cavity in four cases (44%) and involved both the nasal cavity and paranasal sinuses in the remaining five cases. Light microscopic, immunocytochemical, and ultrastructural features served to characterize these tumors as malignant neoplasms of smooth-muscle origin. In contrast with previous studies, immunocytochemistry was employed to differentiate SNTL from other spindle cell malignancies of the region, using newly available monoclonal antibodies to smooth-muscle antigens. Treatment was surgical. Radiotherapy or chemotherapy did not appear to affect the progression of the disease. Furthermore, no relationship was found between the aggressiveness of SNTL and morphologic parameters (eg, mitotic count and tumor size). Instead, prognosis was dependent on the distribution of disease at presentation. Of all 30 patients with SNTL described to date, 10 had the neoplasm confined solely to the nasal cavity. The 10 neoplasms did not recur. We conclude that SNTL may best be regarded as a locally aggressive neoplasm with only limited metastatic potential and that it could be curable by complete surgical excision. PMID- 2242260 TI - Improving diagnostic accuracy of cervical metastases with computed tomography and magnetic resonance imaging. AB - Elective neck dissection in patients with head and neck cancer continues to be controversial. The management of these patients would be greatly facilitated by improvements in predicting cervical metastases. Recent investigations have suggested that computed tomography and magnetic resonance imaging are more sensitive in detecting cervical metastases than physical examination. The Department of Otolaryngology at the Ohio State University Hospitals, Columbus, undertook a prospective study to compare the preoperative sensitivities of physical examination, computed tomography, and magnetic resonance imaging with pathologic findings in 27 patients undergoing neck dissections for head and neck cancer. The results indicate that computed tomography and magnetic resonance imaging were more sensitive (84% and 92%, respectively) than physical examination (75%), although the results did not achieve statistical significance. The sensitivity of combined computed tomography and magnetic resonance imaging was 90%. PMID- 2242261 TI - The in vivo biologic effect of interleukin 2 and interferon alfa on natural immunity in patients with head and neck cancer. AB - Given the association of deficient natural immunity with the risk of metastatic disease, the ability to activate natural killer cell function may have a therapeutic significance. The effect of continuous infusion of interleukin 2 plus intramuscular interferon alfa on natural immune status was, therefore, analyzed in eight patients with head and neck cancer. Also evaluated was the effect of interleukin 2-interferon alfa therapy on lymphokine-activated killer cell activity as well as total lymphocyte count, percent of lymphocyte subsets, and levels of both circulating immune complexes and antibody classes. Both the percent and absolute number of natural killer cells (ie, CD56+ CD3- lymphocytes) within peripheral blood as well as natural killer cell activity against K562 targets increased significantly with treatment. The remaining immune parameters were not significantly altered. The demonstrated capacity to modulate natural immune function supports the potential use of interleukin 2-containing regimens as a preventive measure against metastatic disease in patients with head and neck cancer. PMID- 2242262 TI - Distortion product otoacoustic emissions in normal and impaired adult ears. AB - Distortion product otoacoustic emissions (DPOEs) were recorded in a group of normally hearing subjects (29 ears) and a group of subjects whose conditions were diagnosed as sensorineural hearing loss (23 ears) to study any correlation that might exist between DPOE characteristics and hearing impairment of different configurations. Three different DPOE paradigms have been used to investigate the influence of different test parameters on the DPOE data for normal and hearing impaired ears. All normally hearing ears demonstrated detectable DPOEs, provided that the primary tone level was above a certain value. Hearing-impaired ears produced substantially reduced DPOEs compared with normally hearing subjects when the primary frequencies f1 and f2 corresponded to the region of hearing loss. Our data also suggested that, in general, more than one f2/f1 ratio is needed to examine any particular frequency region. The DPOEs provide frequency-specific information about cochlear function, which after further development, may form a basis for a noninvasive, objective method of evaluating cochlear function. PMID- 2242263 TI - A patient-oriented approach to perilymph fistula. AB - The subject of perilymph fistula is controversial in part because the preoperative diagnosis of perilymph fistula is difficult. Patients suffering auditory and vestibular symptoms secondary to perilymph fistula, therefore, present a dilemma to the practicing physician. In some instances, patients with auditory and vestibular symptoms in the absence of perilymph fistula will be subjected to middle ear exploration without benefit, while in other instances patients with auditory and vestibular symptoms secondary to perilymph fistula will be denied surgical treatment. Auditory and vestibular symptoms are a quality of life issue. Therefore, in an effort to provide care of the highest quality the patient must be actively involved in the decision process. Such involvement can be meaningful only after the patient is carefully counseled as to the pros and cons of surgery, as well as the alternatives. A prognostic paradigm based on the personal experience of one of us (W.L.M.) with perilymph fistula patients is described and is used in patient consultation in an effort to facilitate decision making. PMID- 2242264 TI - Relationships among loudness indexes in cochlear-implant patients. AB - The purpose of the experiment was to determine if the most-confortable-listening (MCL) levels and loudness-discomfort levels (LDLs) can be predicted from threshold measurements obtained from patients with cochlear implants using direct electrical stimulation. Psychophysical measurements of thresholds, MCLs, and LDLs with 125-Hz and 2000-Hz sinusoids were obtained from 16 patients with cochlear implants 1 month after the connection of their ineraid processor (an auditory prosthesis). In general, the correlation coefficients among the loudness indexes obtained with a 125-Hz stimulus were similar to those for a 2000-Hz stimulus. Correlations between thresholds and MCLs were moderate, whereas correlations for thresholds and LDLs were fair. Correlations between MCLs and LDLs were high. This suggests that LDLs cannot be predicted from thresholds. On the other hand, these preliminary data suggest that MCLs may be reliably predicted from thresholds or LDLs to set the gain on a cochlear-implant processor. PMID- 2242265 TI - Audiometric and subjective assessment of hearing handicap. AB - This study compares self-perceived assessment of hearing handicap with audiometrically derived measures of hearing handicap in a sample of elderly persons. Subjects were evaluated by traditional audiometric tests, the Speech Perception in Noise test, and the Hearing Handicap Inventory for the Elderly, a self-assessment questionnaire. Hearing handicap was also calculated by the audiometrically derived American Academy of Otolaryngology (1979) method. Our results are consistent with other studies that indicate a low correspondence between audiometric measures of hearing handicap and self-assessment of hearing handicap. Furthermore, if the Hearing Handicap Inventory for the Elderly is considered the true measure of hearing handicap, our data indicate that the American Academy of Otolaryngology method tends to overestimate handicap among persons with no self-perceived hearing handicap and underestimates handicap among persons with significant self-perceived hearing handicap. PMID- 2242267 TI - Chondrosarcoma of the larynx. Diagnosis with magnetic resonance imaging and computed tomography. AB - Chondrosarcomas are the most common sarcomas of the larynx. They are generally slow-growing lesions with insidious onset of symptoms. We are presenting a case of chondrosarcoma that recurred 10 years after excision of a presumed chondroma. Computed tomographic and magnetic resonance imaging (MRI) scans were performed. Both studies delineated the lesion nicely. To the best of our knowledge, this is the first report on MRI characteristics of chondrosarcoma of the larynx. A review of the literature regarding the use of computed tomography in the management of chondrosarcoma is presented. The MRI characteristics are discussed and the two scanning modalities are compared. Computed tomography is an excellent study in its ability to demonstrate the extent of the lesion within the laryngeal skeleton. Furthermore, it is more highly sensitive than plain roentgenograms in the detection of calcifications that are highly suggestive of chondrosarcoma. Alternatively, MRI can also demonstrate the lesion within the larynx but it has the added advantage of superior contrast resolution of the tumor and paralaryngeal tissues. When the three-dimensional imaging capacity of MRI is considered as well, MRI seems to be the superior study. PMID- 2242266 TI - Synovial chondromatosis of the temporomandibular joint presenting as an intracranial mass. PMID- 2242268 TI - Pathologic quiz case 2. Invasive Alternaria alternata. PMID- 2242269 TI - [Status of children's dental health care in Hillerod after 33 years of implementation]. PMID- 2242270 TI - [Evaluation of a research project designed to improve nutrition of elderly persons who live at home]. PMID- 2242271 TI - [Dental hygiene methods among 11-15-year olds from a health sociological point of view]. PMID- 2242272 TI - Differential response of postischemic diabetic myocardium to a thromboxane mimetic. AB - The postischemic response of control, acute diabetic (48 h) and chronic diabetic (60 days) hearts was studied in isovolumically-perfused rat hearts. Isolated hearts were subjected to 20 min of total global ischemia with reperfusion at preischemic flow rates in the presence or absence of the thromboxane analogue, U 46619. A low concentration (30 nM) of U-46619 which did not produce significant hemodynamic responses prior to ischemia caused significant decreases in isovolumic left ventricular developed pressure and increases in coronary vascular resistance during reperfusion of control but not acute or chronic diabetic hearts. Simultaneously, U-46619 stimulated an additional increment of prostacyclin release during reperfusion of control but not diabetic hearts. Thus, while diabetic hearts may be resistant to certain stimuli of postischemic injury, a caveat results in that the diabetic heart may be jeopardized by a failure to counter other potentially thrombotic or vasospastic factors in vivo by an inadequate compensatory increase in prostacyclin. PMID- 2242273 TI - Prostaglandin E2 evokes intracellular calcium rise in mouse osteoblastic cell line, MC3T3E-1. AB - The effect of prostaglandin (PG) E2 on the intracellular free calcium concentration ([Ca2+]i) in mouse osteoblastic clone, MC3T3E-1 cells, was investigated with the fluorescent probe fura-2. In the growing phase of MC3T3E-1, PGE2 evoked a transient rise of [Ca2+]i in a dose-dependent manner in the range from 0.28 microM to 5.6 microM of PGE2. The elevation of [Ca2+]i induced by PGE2 was not affected by the presence of EGTA. Moreover, PGE2 (5.6 microM) evoked an acute accumulation of intracellular inositol-1,4,5-trisphosphate (InsP3). The absolute content of InsP3 increased from 5.8 pmole/10(6) cells to 19.2 pmole/10(6) cells within 30 sec after the PGE2 treatment. The degree of [Ca2+]i elevation induced by PGE2 was dependent on the day after subculturing. At day 3, the response to PGE2 was the most pronounced during the 8-day experimental periods. These data suggest that PGE2 evoked a [Ca2+]i rise via a phospholipase C InsP3 pathway in osteoblasts, particularly in the growing phase. PMID- 2242274 TI - Stimulation of the 15-lipoxygenase in activated polymorphonuclear neutrophils. Influence of lipoxygenase inhibitors and hydroxyeicosatetraenoic acid derivatives. AB - Hydroxyeicosatetraenoic acids (HETEs) have previously been reported to stimulate the relatively inactive 15-lipoxygenase in A23187-activated human neutrophils to metabolize exogenously added arachidonic acid to 15-HETE. Several aspects of this HETE-induced activation process were examined. Pretreatment of intact PMNs with 3 20 microM 15-HETE, A23187 and the 5-lipoxygenase inhibitor NDGA (or the dual cyclooxygenase/lipoxygenase inhibitor BW755C) followed by [14C]arachidonic acid addition resulted in an unexpected synergistic activation of the cryptic 15 lipoxygenase activity. The ability of several HETE derivatives or analogues to stimulate the inactive 15-lipoxygenase was also investigated. The presence of the hydroxyl group but not its position was essential since 5-, 12- and 15-HETE were approximately equipotent and about ten times more effective than arachidonic acid. 5-HETE was more potent than 5-HETE methyl ester which suggested that a free carboxyl group was important. Both 5-HPETE and 5.15-diHETE were found to be less potent than 5-HETE. The C18 hydroxy fatty acid analogues 9- and 13-HODE were the least effective activators of the PMN 15-lipoxygenase activity that were tested. PMID- 2242275 TI - [Study on the estimation theory of genetic parameters--the estimation method when the parents were relative]. AB - By decomposing the expected mean squares in variance analysis, the estimation methods of genetic parameters are suggested in sib analysis when the parents of the sibs are relatives. Two estimation examples are also given. The results indicate that the estimation values are greater than those estimated by supposing that the parents are not relatives. The closer relative the parents are, the bigger the biased would be. The computer programme PARESTH and PARESTF made it easy to apply the methods. Furthermore, the methods can also be used in variance analysis when the relationships between the levels of each factors are determined. PMID- 2242276 TI - [Characterization of the expression of LDH isozymes genes during non-hibernation Himalayan marmots]. AB - The lactate dehydrogenase (LDH) isozymes from heart, liver, kidney and skeletal muscle in Himalayan marmots (Marmota himalayana robusta) in non-hibernation were investigated in the present experiment. The isozyme patterns were analyzed by means of disc electrophoresis and the ultraviolet enzymatic determination. The following conclusions were obtained: 1. It was found that two expression patterns of LDH genes presented in the skeletal muscle of Himalayan marmots. There was a LDH-B4 band only in one marmots and absent in others. The interindividual polymorphism of LDH isozyme patterns may be attribute to one or more regulator genes controlling synthesis of B-subunit of LDH. 2. LDH zymograms of various tissues of Himalayan marmots showed different subbands. This is presumably due to the existence of both symmetrical and asymmetrical conformers of this tetramer. PMID- 2242277 TI - [Cloning and expression of a promoter function fragment from Thiobacillus thiooxidans in Escherichia coli]. AB - This paper reports a recombinant plasmid pSDR12 which is constructed through the substitution of the EcoRI-HindIII fragment of pBR322 by a specific fragment of chromosomal DNA of T. thiooxidans. After it was transformed into C600, the transformants revealed higher levels of Tc resistance. This result shows that a promoter function fragment from autotrophic bacteria is able to express in Escherichia coil. PMID- 2242278 TI - [Cloning and study on the replication origin of the integrated F plasmid in Escherichia coli]. AB - The replication origin of the integrated F' plasmid was cloned by means of marker rescue. No difference in incompatibility and acridine orange sensitivity was found between the mini-F plasmid constructed from such an origin and the autonomous F' plasmid. Subcloning and comparative restriction enzyme analysis were carried out with the replication origin from the integrated F' plasmid and that from the autonomous F plasmid. No structural difference was found between them. These results suggest that the difference for the dependence of recA gene between the F and F' plasmids dose not come from any difference in structure of their replication origin, but probably from their site of integration on the chromosome. PMID- 2242279 TI - [Distribution of 8 blood group systems in Han ethnic group of Fujian Province, China]. AB - The distribution of 19 red cell's antigens of 8 blood group systems in Han ethnic group in Fujian province, China was investigated. The gene and haloptype frequencies were as follows: p = 0.1936, q = 0.1766, r = 0.6298; p1 = 0.1427; Dia = 0.2830; m = 0.5695, n = 0.4305, S = 0.0339, s = 0.9661, MS = 0.0200, NS = 0.0139, Ms = 0.5500, Ns = 0.4161; Fya = 0.8817; Jka = 0.4767; D = 0.9314, C = 0.7617, E = 0.2357, r' = 0.0686, R1 = 0.6352, R2 = 0.1970, R0 = 0.0605, Rz = 0.0388. Le (a +) phenotype frequency = 7.94%. PMID- 2242280 TI - [Molecular evolution and a speculative carcinogenesis mechanism for ras p21]. AB - Ten of amino acid sequences of ras p21 which come from human, fruit fly, yeast, Dictyostelium and virus were collected and analyzed. Data analysis indicates that: 1. the mean duplicate rate of ras p21 is approximately 2.78 x 10(-9) per gene per year for concerted evolution; 2. the mean amino acid replacement of p21 is about 2.23 x 10(-10) per year. It also shows that v-Has and v-Kis were derived from c-H-ras1 and c-K-ras2, respectively, and that c-H-ras1, c-K-ras2 and c-N-ras come from the same ancestor. These result are in accordance with the experimental results reported by other authors. According to the view of Fitch et al., we present here a speculative view for carcinogenesis mechanism the hypothesis for covarions and invarions, by which, the codon 12 or 61 mutated in p21 may be responsible for last one or more steps in carcinogenesis. PMID- 2242281 TI - [Genetic differentiation of red cell blood groups in fourteen populations of China]. AB - Genetic differentiation among ethnic groups of China is analysed and discussed on the basis of gene frequency data of red cell blood groups. The degree of differentiation, measured by FST analysis of Wright, shows that the MNs system has much higher FST values than those of ABO system. This result is quite different from that calculated by Cavalli-Sforza (1966) on a worldwide basis. Generally speaking, the Rhesus, Lewis and MNSs systems are more useful in anthrological and human genetic studies on Chinese populations for they have a great variation. The genetic difference within and between 12 ethnic groups, namely, Han, Hui, Mongolian, Uygur, Zhuang, Yi, Korean, Manzu, Bai, Tibetan, Dong and Gaoshan, are also analysed. On the basis of gene frequencies of 15 blood group loci which are all polymorphic at least in one of 12 above-mentioned ethnic groups, the net coden difference between populations is calculated by method of Nei and Roychoudhury (1974), and phylogenetic dendrograms are constructed on the basis of net coden differences. Results obtained with the method of gene differentiation coefficient of Nei (1973) and that of Shannon information measure of Lewontin (1972), indicate that the genetic difference between ethnic groups of China accounts for only about 2% of the total genetic variation and is much smaller than that within ethnic groups. Genetic difference between three races of human being is also discussed by taking the Han living in northern China, as typical Mongoloids. On the basis of analysis of gene frequency data of 15 blood group loci, it is concluded that Mongoloids are genetically closer to black people than to white people. PMID- 2242282 TI - [Cytogenetic effects of attenuated live measles vaccine on male mice]. AB - The cytogenetic effects of attenuated live measles vaccine on somatic and germinal cells of C57BL/6J mice were studied. The frequencies of micronuclei of polychromatic erythrocytes, nucleated cells, chromatid breaks, fragments in bone marrow cells, and micronuclei of spermatids in testes were increased, which have dose- and time-dependent relationship. However, there were no statistical difference between the treated and control mice in chromosomal breaks and fragments of spermatogonia primary and secondary spermatocytes. The results and their possible biological significance were also discussed. PMID- 2242283 TI - [Construction of promoter probe vector pFDC4 and gene expression vector pFDC11 with high transformation efficiency in Bacillus stearothermophilus]. AB - A 0.5kb fragment from Sau3A-digested total DNA of Bacillus stearothermophilus CU21 was cloned with the vector pPGV5, a derivative of pPL703. The insertion of this fragment can activate the expression of the promoteless cat-86 gene on the cloning vector in both B. stearothermophilus and Bacillus subtilis hosts. When the 0.54 kb fragment is present in pPGV5 in either orientation, the transformation efficiency of the plasmid is increased about 10(3) to 10(4) fold in CU21 protoplasts. Southern hybridization showed this 0.54 kb fragment was homologous with a 1.6kb fragment, which was shown by Imanaka et al. (1984, J. Gen. Microbiol. 130, 1399-1408) to originate in a cryptic plasmid resident in CU21 and to enhance the transformat on efficiency of another plasmid. With this 0.54kb fragment a new promoter probe vector pFDC4 and a gene expression vector pFDC11 were constructed. Both can transform the CU21 recipient with high efficiency. PMID- 2242284 TI - [Purification of autographa californica nuclear polyhedrosis virus DNA and cloning of the polyhedrin gene]. AB - Autographa califonica nuclear polyhedrosis virus (AcNPV) DNA from larvae of lepidopteran infected by AcNPV has been isolated. The EcoRI fragments of AcNPV DNA have been cloned using plasmid pBR325 as a vector. The polyhedrin gene fragment containing recombinant plasmid pAc-18 was isolated through in situ hybridization. For the convenience of further construction the EcoRI insertion fragment was cloned into pUC-8. Thus plasmid pUAc-2 was obtained. The results of restriction mapping of pAc-18 and pUAc-2 and part of the sequence were reported. The polyhedrin promotor was known to be one of the most effective promotor useful in the expression of foreign genes in the insect cells. PMID- 2242285 TI - [The construction of shuttle plasmid vector of Streptomyces and E. coli]. AB - A shuttle plasmid vector, pSE-3 was constructed using the Streptomyces plasmid pIJ486 and E. coli plasmid pGEM-3 digested with BgIII and BamHI respectively. The shuttle plasmid pSE-3 could replicate and express its neomycin resistance in both Streptomyces and E. coli well. The pSE-3 has opposed promoters containing bacteriophage ST6 and T7, the restriction enzyme digestion showed that the pSE-3 has a single site with HindIII and EcoRI respectively, it is very useful for the cloning and expression of the valuable gene inserts. The pSE-3 is stable in both of Streptomyces and E. coli after re-transformed pSE-3 is re-transformed from Streptomyces into E. coli and some 50 generations are propagated. PMID- 2242286 TI - Strategies for obtaining preventive services reimbursement. PMID- 2242287 TI - Paying for preventive care: moving the debate forward. PMID- 2242288 TI - The predictive value of forearm bone mineral content measurements in men. AB - Six hundred and fifty-four men had their bone mineral content (BMC) measured with single photon absorptiometry during 1970-1976. All roentgenograms 1975-1985 (11 years) were registered and thus all falls requiring roentgen examinations. BMC was found to be of predictive value in ages below 70-80 with regard to future fragility fractures. Other characteristics were more falls, less grip strength, and weight. A history of previous vertebral fracture and cerebral disorder were also predictive. Men with only nonfragility fractures showed no differences compared to the nonfracture population. PMID- 2242289 TI - Increased mechanical strength of healing rat tibial fractures treated with biosynthetic human growth hormone. AB - The effects of biosynthetic human growth hormone on the biomechanical properties of healing tibial fractures and intact bones in the rat were studied after 20 and 40 days of healing. Growth hormone, 2.0 mg per kg per day, was given subcutaneously in two daily doses. Control animals were injected with a corresponding volume of saline. After 20 days of fracture healing, there were no differences in mechanical properties between the healing fractures and intact bones. After 40 days, the ultimate load and maximum stiffness of the fractures of the b-hGH injected animals had increased to more than 400% of the corresponding values of the saline injected animals, and ultimate stress and energy absorption at ultimate load had increased to 270% compared with the saline injected animals. Ultimate load, stiffness, and energy absorption of the intact bones increased in the b-hGH injected animals, but no differences were found in ultimate stress values or normalized energy, indicating that the changes in the intact bones were quantitative phenomena. PMID- 2242290 TI - A computerised technique for the quantitative assessment of resorption cavities in trabecular bone. AB - A computerised technique is described for the quantitative assessment of resorption cavities in iliac trabecular bone. Using an Ibas II image analyser, the original bone surface, eroded by bone resorbing cells, is reconstructed using a curve fitting technique that maintains a smooth continuity with the trabecular bone on either side of the cavity. Resorption depths are measured using an interactive elastic circle; all identified cavities are measured regardless of whether or not resorption is complete, and the measurements made include mean and maximum cavity depth, cavity length, area, and adjacent trabecular widths. Results in 13 normal subjects are presented. The technique is reproducible, simple to operate, relatively rapid, and can be applied to less sophisticated image analysis systems. PMID- 2242291 TI - Prostaglandin E2 enhances cortical bone mass and activates intracortical bone remodeling in intact and ovariectomized female rats. AB - To assess the efficacy of prostaglandin E2 (PGE2) in augmenting cortical bone mass, graded doses of PGE2 were subcutaneously administered for 30 days to seven month old sham-ovariectomized (SHAM) and ovariectomized (OVX) rats. Both groups were operated at three months of age. Histomorphometric analyses of double fluorescent labeled tibial shafts were performed on basal control, OVX, and SHAM rats treated with 0, 0.3, 1, 3, and 6 mg PGE2/kg/d for 30 days. Baseline aging data showed increased cortical tissue and cortical bone area and reduced bone formation parameters at the periosteal and endocortical bone envelopes between three and eight months of age. The tibial shafts of OVX rats compared to SHAM controls showed elevated periosteal mineral apposition rate and endocortical bone formation parameters. PGE2 administration to OVX and SHAM rats increased cortical bone by the addition of new circumferential bone on the endocortical and periosteal surfaces, as well as woven cancellous bone in the marrow region. Stimulated osteoblastic recruitment and activity enhanced bone formation at all bone surfaces. The new bone was both lamellar and woven in nature. PGE2 treatment also activated intracortical bone remodeling (not seen in untreated eight-month old rats), creating a porous cortex. Thus, PGE2 administration activated cortical bone modeling in the formation mode (A----F), as well as intracortical bone remodeling (A----R----F). PGE2 administration to OVX rats resulted in more intracortical bone remodeling, periosteal bone formation, and new cancellous bone production than observed in PGE2 treated controls. The findings that PGE2 administration to OVX and intact female rats increases cortical bone mass, coupled with observations that mouse, rat, dog, and man respond similarly to PGE2, suggest that PGE2 administration may be useful in the prevention and treatment of postmenopausal osteoporosis. PMID- 2242292 TI - The effects of the major vitamin D metabolites upon the resolution of osteomalacia in uremic adult rats. AB - We have previously shown that an osteomalacia dependent upon both a low phosphorus diet and uremia (five-sixth nephrectomy) can be produced rapidly in rats. This is associated with hypophosphatemia and elevated 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). In order to investigate the role of exogenously administered vitamin D metabolites upon the resolution of this osteomalacia, 72 male Sprague Dawley rats weighting 320 +/- 20 g were subjected to a two-step, subtotal nephrectomy and subsequently fed a diet with low (0.03%) phosphorus (LP) for seven days. Groups of six rats each were then either continued on the LP diet, or switched to a nutrient-matched diet with normal (0.3%) phosphorus (NP) for an additional 10 days. During this time, the rats were infused daily with either: 27 ng 1,25(OH)2D3; 81 ng 24,25 dihydroxyvitamin D3 (24,25(OH)2D3); 135 ng 25 hydroxyvitamin D3 (25(OH)D3); both 27 ng 1,25(OH)2D3 and 81 ng 24,25(OH)2D3; or placebo. Dietary phosphorus repletion was found to reverse the osteomalacia by decreasing the growth plate thickness, the osteoid surface and volume, the osteoid maturation time, serum calcium, and plasma 1,25(OH)2D3, and by increasing the mineralizing surface, bone formation rate, and serum phosphorus. The osteomalacia was also reversed in phosphorus-repleted rats treated with 24,25(OH)2D3, with no additional effects attributable to the 24,25(OH)2D3 itself. Osteomalacia in phosphorus-repleted rats treated with 25(OH)D3 or 1,25(OH)2D3 was only partially reversed; healing was interpreted to be impaired by the elevated plasma 1,25(OH)2D3 levels present in these rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242293 TI - Distribution of type I and type II collagen gene expression during the development of human long bones. AB - The temporal and spatial gene expression of collagen type I and type II during the development of the human long bones was studied by the technique of in situ hybridization covering the period from the cartilagenous bone anlage to the formation of a regular growth plate in the newborn. Analysis of the early stages around the seventh week of gestation revealed for type II collagen a strong hybridization signal limited to the chondrogenic tissue. The surrounding connective tissue and the perichondrium showed weak type I collagen expression, while the zones of desmal ossification like the clavicle gave a strong signal. Beginning with the eighth week of gestation, type I collagen mRNA was detectable in newly formed osteoblasts at the diaphysis and appeared along with the formation bone marrow, in the areas of enchondral ossification. Parallel to the development of the different zones of cartilage differentiation, a specific pattern of type II expression could be observed: type II was mainly found in the chondrocytes of the hypertrophic zone and to a lesser degree in the zone of proliferation, while the resting zone and the zone of provisional calcification showed little activity. This segregation of type II expression was most pronounced in the early stages of cartilage calcification and in the growth plate of the newborn. PMID- 2242294 TI - A band of F-actin containing podosomes is involved in bone resorption by osteoclasts. AB - Isolated rabbit osteoclasts cultured on devitalized thin bone slices excavate resorption lacunae that can be visualized with brightfield or phase-contrast microscopy. Superimposition of the brightfield images of such resorption lacunae and the fluorescence images of the corresponding osteoclasts after fixation and staining with rhodamine-conjugated phalloidin revealed that a bright fluorescent band of F-actin-containing podosomes precisely outlined the resorption lacunae in stationary osteoclasts. When the resorption lacunae were being extended laterally, the clearly delineated band of podosomes corresponded to the advancing edge of the resorbing osteoclast and the most recently excavated part of the lacunae. Reshaping and reorganization of the bright bands preceded development of the lateral boundary of the lacunae. Podosomes forming these bands were highly dynamic, changed in size and location, and appeared and disappeared continuously. Their lifespan varied between 2 and 12 min. Similar bands were also seen in vivo in bone-resorbing osteoclasts on the endocranial surface of growing calvariae. Podosomes disappeared in osteoclasts treated with calcitonin, resulting in the disruption of the fluorescent bands. Our results suggest that podosomes are an essential part of the resorption apparatus of osteoclasts. PMID- 2242295 TI - Stimulation of bone formation in vivo by transforming growth factor-beta: remodeling of woven bone and lack of inhibition by indomethacin. AB - Local effects of transforming growth factor-beta (TGF beta) on bone have been investigated in growing mice. The influence of indomethacin on TGF beta effects was also examined. Five daily injections of TGF beta-1 or -2 were administered subcutaneously over the frontal and parietal bones of seven-week-old mice. In animals treated with TGF beta alone or TGF beta and indomethacin, then killed on day 19 (day 1 = day of first TGF beta injection), the combined frontal and parietal bones were heavier and the frontal bones were thicker than in controls. On day 4, multiple layers of differentiating osteoblasts were visible in the periosteum of calvariae from TGF beta-treated animals. On day 8, highly vascularised periosteal woven bone was seen in the calvariae of TGF beta-treated animals. On day 19 (14 days after the last injection) the woven bone had been partially remodeled into lamellar bone containing bone marrow, and was still actively being remodeled. The histological appearance of bones from animals treated concurrently with TGF beta and indomethacin was identical to that of animals treated with TGF beta alone, and there appeared to be no difference between TGF beta-1 and TGF beta-2. Thus TGF beta-stimulated bone formation in vivo is a long term effect that appears to be independent of prostaglandins. Osteoclast counts in sections of TGF beta-treated animals were not elevated on day 4, although at this stage effects on osteoblastic cells were already morphologically apparent. Osteoclast counts in TGF beta-treated bones were significantly increased over control values on days 8 and 19.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242296 TI - Patient education, the challenges and rewards. PMID- 2242297 TI - Hypersensitivity reactions and endotoxins. PMID- 2242298 TI - Primary nursing in a nephrology setting: the Credit Valley Hospital experience. PMID- 2242299 TI - Patient education, the challenges and rewards. PMID- 2242300 TI - Life in the slow lane ... proceed with caution. PMID- 2242302 TI - XXIV Annual Meeting of the European Society for Paediatric Nephrology. 30 September-October 1990, Rome, Italy. Abstracts. PMID- 2242301 TI - Modulation of mammalian O6-alkylguanine-DNA alkyltransferase in vivo by O6 benzylguanine and its effect on the sensitivity of a human glioma tumor to 1-(2 chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. AB - Experiments were carried out in mice and hamsters to determine whether the activity of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, in tissues and tumors was reduced by treatment with O6-benzylguanine in vivo. Following intraperitoneal injection of O6-benzylguanine, there was a rapid and complete loss of alkyltransferase activity in both livers and kidneys of mice and hamsters. The activity in mouse tissues was slowly restored, reaching pretreatment activities at 16 hr and 72 hr after injection of O6-benzylguanine at 10 mg/kg or 126 mg/kg, respectively. The activity in hamster liver was restored at a significantly lower rate, reaching less than 20% pretreatment activity 72 hr after treatment with 100 mg/kg of O6-benzylguanine. The efficient reduction of alkyltransferase activity by O6-benzylguanine was in sharp contrast to the inability of O6-methylguanine to bring about similar reductions. Activities dropped to about 55% of pretreatment activities in several mouse organs 4 hr after treatment with 126 mg/kg of O6-methylguanine compared to a more than 90% reduction in activity in animals after treatment with O6-benzylguanine. The sensitivity of SF767 cells to meCCNU after treatment with O6-benzylguanine was increased substantially. Furthermore, treatment of nude mice carrying SF767 tumor with 60 mg/kg of O6-benzylguanine prior to either 7.5 or 15 mg/kg of meCCNU led to significant inhibition of tumor growth. These studies indicate that O6 benzylguanine is a suitable compound for use in experiments to examine the role of the alkyltransferase protein in vivo in counteracting the effects of alkylating agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242303 TI - Testicular function following cyclophosphamide treatment for childhood nephrotic syndrome: long-term follow-up study. AB - Testicular function of 17 males treated in childhood or adolescence for nephrotic syndrome (NS) with cyclophosphamide (CY) for a mean time of 240 days (mean total dosage of 16.4 g or 641 mg/kg body weight) was evaluated at a mean time of 11.8 years after treatment. Five were azoospermic, 1 oligospermic, and 11 normospermic. There was a significant inverse correlation of sperm density with CY dosage and duration of treatment. All patients had undergone normal pubertal development and had normal sexual characteristics. Both basal and gonadotropin releasing hormone-stimulated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were significantly raised in oligo- and azoospermic patients. Raised basal and peak FSH and LH concentrations in normospermic patients with a sperm count of less than 40 x 10(6)/ml were in keeping with impairment of two testicular components. However, mean basal plasma testosterone levels and mean peak plasma testosterone responses to human chorionic gonadotropin (HCG) did not differ significantly between patients and controls. Although LH responses to gonadotropin-releasing hormone suggested compensated Leydig cell failure in patients with testicular tubular damage, secretory reserve capacity of these cells, estimated by a HCG stimulation test, was preserved. Further follow-up is required to ascertain whether in these patients Leydig cell failure will develop with time. PMID- 2242304 TI - Pituitary-gonadal function in women following cyclophosphamide treatment for childhood nephrotic syndrome: long-term follow-up study. AB - Ovarian and pituitary-gonadal function was evaluated in 12 women who were treated with cyclophosphamide for nephrotic syndrome before or during puberty. The mean age at the start of treatment was 8.7 years; the mean total dose of cyclophosphamide was 439 mg/kg body weight; and the mean follow-up time was 12.3 years. The investigations included detailed developmental, menstrual and fertility histories; general and gynaecological examinations; basal levels and follicle-stimulating hormone and luteinizing hormone responses to gonadotropin releasing hormone, and plasma oestradiol determinations. All patients had normal pubertal development and regular menstrual patterns. Two had borne healthy children. Although hormonal studies did not show obvious ovarian or pituitary gonadal dysfunction, further follow-up is required to ascertain whether the patients with the most prolonged treatment undergo a premature menopause. PMID- 2242305 TI - Evaluation of chlorambucil therapy in steroid-dependent and cyclophosphamide resistant children with nephrosis. AB - A prospective study was performed to evaluate the efficacy of chlorambucil in inducing long-term remission in children with steroid-dependent or cyclophosphamide-resistant primary nephrotic syndrome (NS). The 16 steroid dependent children had a relapse rate of 5.3/patient per year (range 4-8) and a mean age of 8.4 years (range 2-13). The chlorambucil dosage was 0.2 mg/kg per day for a total of 8 weeks. Nine patients (56%) remained in complete remission for an average of 39.2 months (range 16-70). The interval to the first relapse in the remaining 7 ranged from 4 to 41 months and the relapse rate decreased significantly to 0.6 relapses/patient per year (P less than 0.05). Five children had steroid- and cyclophosphamide-resistant NS, 4 with focal segmental glomerulosclerosis and 1 with mesangiol proliferative glomerulonephritis. Chlorambucil was given in a dose of 0.2 mg/kg per day for 8-16 weeks. Complete remission was obtained in 4 patients; 2 patients relapsed. No serious long-term complications were observed in our patients. PMID- 2242306 TI - Renal amyloidosis in juvenile chronic arthritis: evolution after chlorambucil treatment. AB - Over a 22-year period, eight patients affected with severe systemic or polyarticular juvenile chronic arthritis (JCA) developed systemic amyloidosis with nephrotic syndrome. They were treated with chlorambucil over 5-192 months (mean = 44 months). With treatment, an abrupt decrease in the severity of JCA was observed in six patients but two patients were chlorambucil resistant. After a mean follow-up period of 10 years from onset of renal symptoms, one chlorambucil resistant patient died of end-stage renal failure; two patients have a persistent nephrotic syndrome; and five patients are free from proteinuria, of whom one has developed hypertension. A good correlation was observed between the response of the rheumatic disease to chlorambucil treatment and the clinical course of renal symptoms. Fourteen renal biopsies were performed in these eight patients. In all, amyloid deposits were of the AA type, which persisted on repeat biopsies. In addition, 15%-60% of glomeruli had become globally sclerotic by the second or third biopsies. At the ultrastructural level, modifications in the structure of amyloid deposits and reparative changes of the glomeruli, characterized by partial restoration of glomerular architecture, were observed in three patients with a favourable clinical course. PMID- 2242307 TI - Pharmacokinetics of prednisolone in children with the nephrotic syndrome. AB - The aim of this study was to establish whether the criteria for the clinical effectiveness of steroids are correlated with the pharmacokinetics of prednisolone in children treated with prednisone during an attack of idiopathic nephrotic syndrome (INS). Thirteen patients with nephrosis were included. Prednisolone, prednisone and cortisol levels were measured using a specific high performance liquid chromatography assay after an oral dose of 1 mg/kg body weight of prednisone taken at the onset of the disease. All the pharmacokinetic parameters, including the conversion of prednisone to prednisolone were similar to the data already published in children with INS. No correlation was found between the values of pharmacokinetic parameters and criteria of clinical effectiveness. Hypo-albuminaemia was significantly correlated with the area under the plasma-concentration curve but not with the elimination half-life of prednisolone. Moreover, the prednisolone elimination half-life correlated with the urinary excretion of 17-hydroxycorticosteroids achieved in the first 6 h. The present study suggests that routine measurements of prednisolone kinetics do not help when assessing the treatment of children with INS. PMID- 2242308 TI - Ciclosporin treatment in children with steroid-dependent nephrotic syndrome. AB - We report our experience with ciclosporin (CS) treatment in 18 children with steroid-dependent nephrotic syndrome. CS was started at 3-5 mg/kg per day after the patients had attained remission with steroid therapy, and was adjusted to maintain a trough blood level of between 250 and 600 ng/ml, being administered for 6 months. Although 1 patient dropped out of the study because of renal dysfunction, the remaining 17 children completed the full trial. No relapse occurred during the 6-month period of CS treatment, and it was possible to discontinue steroid therapy in all patients. However, after discontinuation of CS treatment, nephrotic syndrome relapsed in 16 patients and 14 again had frequent relapses and became steroid-dependent, as before CS treatment. The effect of CS in maintaining remission from steroid-dependent nephrotic syndrome was thus dependent on continuation of CS treatment. Although several side-effects occurred during CS treatment, they were not so serious as to necessitate discontinuation of treatment, except in 1 patient, and all of these side effects were reversible. CS is therefore a new agent for the management of children with steroid-dependent nephrotic syndrome in place of corticosteroid and alkylating agents, although long-term maintenance therapy may be necessary for maintaining longer remission. PMID- 2242309 TI - Human leucocyte antigens in idiopathic nephrotic syndrome in children. AB - An association of the idiopathic nephrotic syndrome (NS) with certain human leucocyte antigens (HLA) has been reported repeatedly. The aim of this study is to characterize further the clinical and histological features of patients with NS in relation to their HLA phenotypes. HLA antigens were determined in 132 paediatric patients with NS. In 91 steroid-sensitive patients (usually associated with minimal glomerular changes), the antigen frequencies of HLA-DR3, HLA-DR7, and HLA-B8, -DR3 combined were significantly increased compared with controls. The strongest association was observed with the combined occurrence of HLA-B8, DR3, -DR7 (relative risk 21.5). This association and that with HLA-DR3 alone were strongest in the presence of frequent relapses and steroid dependence compared with children without or with infrequent relapses. The pattern of HLA antigens was similar in the 57 steroid-sensitive patients with biopsy-proven minimal glomerular changes. In 41 children with steroid-resistant NS (usually associated with focal segmental glomerulosclerosis) a similar trend for increased antigen frequencies was found but the data were significant only for the combined occurrence of HLA-B8, -DR3 and -DR7. In all patients combined the frequency of the HLA associations was significantly lower when the age of onset was greater than 8 years compared with that of younger patients. It is concluded that the immunogenetic background of the steroid-sensitive and steroid-resistant NS is different and age-dependent. PMID- 2242310 TI - Acute glomerulonephritis--changing patterns in Singapore children. AB - This study compared the pattern of acute glomerulonephritis (AGN), a disease known to be influenced by socioeconomic and environmental factors, in children 12 years and under, for the years 1971 and 1985. All children admitted to the four major paediatric departments with haematuria and at least two of the following (oedema, hypertension or oliguria) had an initial diagnosis of AGN. A sample population from one unit from 1980 to 1984 showed that over 70% of these children had evidence of a post-streptococcal aetiology. In 1971, 411 children were admitted with AGN, as compared with only 58 in 1985. The age-sex-race standardized rates for 1971 and 1985 were 0.632 and 0.023/1,000 children 12 years and under, respectively (P less than 0.001). The mean age of presentation was lower in 1971. Over this period, Singapore saw a threefold rise in the gross national product, accompanied by rapid urbanization. On analysis of the housing pattern, only 31% of the children lived in high-rise apartments in 1971, in contrast with 86% in 1985 (P less than 0.001). The majority of non-apartment dwellers had homes in rural districts. From an epidemiological perspective, factors which could have led to the highly significant decline in prevalence of AGN in Singapore children included improvement in the socioeconomic status and health care system, and urbanization of the country. PMID- 2242311 TI - Quantitation of vesico-ureteral reflux by radionuclide cystography and urodynamics. AB - A method is described for the quantitation of vesico-ureteral reflux by synchronous combined direct radionuclide cystography and urodynamics. Intravesical pressures and volumes are co-ordinated with volumes of reflux. Peak reflux volumes in 11 children diagnosed as having severe (grades 3-4) reflux on conventional contrast cystography ranged from 1 to 50 ml/kidney. A number of different patterns of reflux were observed. Reflux may occur progressively throughout low pressure filling or incrementally with unstable bladder contractions. Reflux during voiding may be maximal as detrusor pressure falls. The method requires wider application to explore the potential for a functional classification of the reflux problem. PMID- 2242312 TI - The pattern of congenital renal anomalies associated with neural tube defects. AB - It has been suggested that there may be a consistent pattern of congenital renal abnormalities related to a particular sensory level in patients with spina bifida. In assessing 163 spina bifida patients by reviewing intravenous pyelograms (without knowledge of clinical details) and correlating with the level of sensory loss (without knowledge of radiological findings), the prevalence of renal abnormalities was similar, but a consistent pattern was not confirmed. PMID- 2242313 TI - Urinary oxalate and glycolate excretion in healthy infants and children. AB - The molar ratios of oxalate and glycolate over creatinine were determined in single urine samples of 26 infants and 27 children aged 1-5 years. In 135 children aged 5-16 years, two urine specimens were collected, one before breakfast and one at noon. Oxalate was determined by oxalate oxidase, and glycolate was measured by a colorimetric method (improved chromatotropic acid- sulphuric acid assay after prior purification by cation and anion exchanger). Both ratios (expressed in mmol/mol creatinine and analysed on a log-normal basis) were highest in infants 0-6 months old [mean oxalate 147 (95% confidence interval: 60-360), mean glycolate 175 (72-425)]. The mean oxalate ratio was 72 mmol/mol (29-174) at the age of 7-24 months, 44 (19-101) at the age of 2-5 years and 22 (12-40) in adolescents aged 16 years. Molar glycolate ratios were higher, but disclosed the same pattern. Oxalate and glycolate ratios in fasting urines did not differ significantly from those in noon samples (except glycolate in the oldest age group). Oxalate ratios correlated well with glycolate ratios in children up to 5 years of age only. Random urine samples are thus suitable for screening. However, interpretation of data requires use of age-specific reference values that are based on comparable methods. PMID- 2242314 TI - Why does deficiency of NaCl affect growth? PMID- 2242315 TI - One year's experience with recombinant erythropoietin in children undergoing continuous ambulatory or cycling peritoneal dialysis. AB - Fourteen patients (aged 5.9-22.1 years) undergoing continuous ambulatory or cycling peritoneal dialysis were treated with recombinant human erythropoietin (rhEPO), which was given intravenously once a week at a dosage of 300 units/kg. The mean haematocrit level increased from 18.5% to 27.5% and the reticulocyte count from 19% to 62% within 1 month. After an average time of 3.1 months rhEPO dosage could be adjusted to 100 units/kg per week to keep the haematocrit level at 30%. Only 1 patient had an exacerbation of hypertension, which required a dosage reduction; other side-effects were not noted. PMID- 2242316 TI - The renal functional and structural consequences of corticosteroid and angiotensin-converting enzyme inhibitor therapy in chronic puromycin aminonucleoside nephropathy. AB - Glomerular diseases are characterized by increased urinary protein excretion. Treatment of this abnormality frequently involves administration of corticosteroids and angiotensin-converting enzyme inhibitors. There has been much recent interest in the potential impact of these drugs on progressive renal dysfunction, since they have opposing effects on intraglomerular hemodynamics. Therefore, we investigated the effect of methylprednisolone or captopril treatment on animals with chronic puromycin aminonucleoside nephropathy. In rats given a single injection of puromycin aminonucleoside, 15 mg/100 g body weight, both methylprednisolone and captopril significantly reduced proteinuria at 6 months [83 +/- 14 untreated (n = 7), 34 +/- 6 with methylprednisolone (n = 8), and 6 +/- 1 mg/24 h with captopril (n = 5), P less than 0.001]. Segmental glomerulosclerosis occurred with equal frequency in the untreated (7.8 +/- 2.3%) and methylprednisolone-treated rats (5.0 +/- 1.11%), but was significantly reduced by the administration of captopril (1.0 +/- 0.5%, P less than 0.001). We conclude that in chronic puromycin aminonucleoside nephropathy, treatment with corticosteroids reduces proteinuria without increasing the incidence of segmental glomerulosclerosis. Therapy with an angiotensin-converting enzyme inhibitor substantially decreases proteinuria and lessens the severity of glomerular scarring. PMID- 2242317 TI - Successive lectin-binding changes within the collecting duct during post-natal development of the rabbit kidney. AB - Histological sections of neonatal rabbit kidney of various ages were analysed to study the ontogeny of the collecting duct system. In addition, the sections were incubated with fluorescent wheat germ (WGA) and peanut agglutinin (PNA) to investigate the terminal differentiation of collecting duct cells. With both lectins we found different binding behaviours in the three segments of the collecting duct anlagen, the ampullary bud, the ampullary neck and the collecting duct. During the observed steps in development the lectin-binding pattern in the collecting duct and the ampullary neck appeared unchanged. In the collecting duct most cells reacted with WGA and only a few with PNA, while in the ampullary neck all cells bound both WGA and PNA. In the ampullary bud, however, the lectin binding pattern changed between unlabelled and completely labelled stages with both lectins. The results indicate that both intercalated and principal cells originate from a common precursor cell. PMID- 2242318 TI - Leukaemia-associated hypercalcaemia in a 10-year-old boy: effectiveness of aminohydroxypropylidene biphosphonate. AB - A 10-year-old boy with leukaemia-associated hypercalcaemia was treated with aminohydroxypropylidene biphosphonate (AHPrBP previously APD) in a total dosage of 60 mg over 5 days, when the condition failed to respond to rehydration and frusemide and no sustained effect was produced by haemodialysis with a calcium (Ca)-free dialysate. Bone films showed no lytic lesions, and AHPrBP, which is a potent inhibitor of osteoclast-mediated bone resorption was well tolerated and induced a rapid and sustained fall in plasma Ca (from 3.42 to 2.07 mM in 5 days). Plasma magnesium and alkaline phosphatase remained normal. The results could have been affected by other drugs [vincristine, cyclophosphamide, zorubicin (Rubidazone) L-asparaginase and prednisone] which were simultaneously administered. However, the observation that: (1) the response curve of plasma Ca was similar to that reported when AHPrBP was used alone, (2) there was complete inhibition of urinary Ca excretion and (3) hypocalcaemia occurred suggests that AHPrBP was the major cause of the reduction in plasma Ca. AHPrBP should be considered a potential therapy for hypercalcaemia in childhood malignancy. PMID- 2242319 TI - Assessment of tubular function in neonates using urinary beta 2-microglobulin. AB - Renal proximal tubular function was assessed in neonates by measuring urinary beta 2-microglobulin (beta 2M) concentrations on days 1, 4, 7, 14 and 28. Values were elevated in stable preterm low-birthweight (LBW) neonates but not in stable term LBW neonates, suggesting that proximal tubular maturation is related to gestational age rather than birthweight. The urinary beta 2M was significantly increased on day 1 in neonates with the meconium aspiration syndrome but was not significantly different from normal subsequently. This indicated that although the proximal tubular cells may be susceptible to perinatal hypoxia, they maintain a remarkable capacity to recover in a relatively short period. Neonates with transient tachypnoea of the newborn had normal urinary levels of beta 2M indicating their renal tubular function was not impaired. PMID- 2242320 TI - Ultrasonographic findings in congenital nephrotic syndrome. AB - This report documents a case of biopsy-proven congenital nephrotic syndrome, Finnish type (CNF), which was initially misdiagnosed as infantile polycystic kidney disease based on ultrasonographic findings. We report this to further describe ultrasonographic features of CNF, and to point out that these two diseases may have similar features on ultrasound. PMID- 2242321 TI - Nephrotic syndrome in Saudi children clinicopathological study of 150 cases. AB - The study includes 150 children with primary nephrotic syndrome (NS), aged 16 months to 13 years with a median age of 5 years. The male to female ratio was 2:1 and the familial occurrence was 6%. Amongst 48 biopsied patients, 19 (39%) had focal segmental glomerulosclerosis, 17 (35%) had diffuse mesangial proliferative glomerulonephritis (MesPGN) and 10 (21%) had minimal change nephropathy. About 90% of patients responded to the initial prednisolone therapy. Subsequently 45% of steroid-sensitive patients had frequent relapses, 23% had no relapses, 21% had infrequent relapses and 5% became steroid resistant. Saudi children with primary NS showed no differences as regards age at onset, male predominance and response to initial prednisolone therapy when compared with published data from other countries. However, the higher incidence of familial occurrence, the relatively high frequency of MesPGN, the rarity of infection-related NS and a decreasing incidence of serious infections with improving socio-economic status were all noteworthy. PMID- 2242322 TI - Is it correct to supplement patients with nephrotic syndrome with vitamin D and calcium? PMID- 2242323 TI - Hypertension in Jordanian children: a retrospective analysis of 70 cases. AB - Seventy patients, aged 1-20 years, were seen at Jordan University Hospital with high blood pressure (BP) over a 3-year period. BP values ranged from 140 to 230 mmHg for systolic pressure and from 90 to 130 mmHg for diastolic pressure. Essential hypertension was seen in only 6 patients (8.6%); secondary hypertension (n = 64 or 91.4%) was due to renal parenchymal diseases (RPD) in 46 patients (65.7%), reno-vascular lesions in 8 (11.4%), renal transplantation in 5 (7.2%), teenage pregnancy in 4 (5.7%), and phaeochromocytoma in 1 patient (1.4%). The aetiologies of RPD were as follows: end-stage renal disease requiring dialysis in 14 patients, acute glomerulonephritis in 14, idiopathic nephrotic syndrome in 10, chronic renal insufficiency in 5, and polycystic kidney in 3 patients. Surgical cure of hypertension was achieved in 5 of the children with reno-vascular lesions and in the patient with phaeochromocytoma. PMID- 2242326 TI - The 1989 report of the North American Pediatric Renal Transplant Cooperative Study. AB - This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1-5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6-12 and 12-17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1 year survival estimate is 0.94. There have been 9 malignancies. PMID- 2242325 TI - The rheumatic poison: a survey of some published investigations of the immunopathogenesis of Henoch-Schonlein purpura. AB - Laboratory studies of the pathophysiology of Henoch-Schonlein purpura (HSP) have become more numerous in recent years with the recognition of the disease's links with the mucosal immune system in general and IgA nephropathy in particular. There are weak genetic associations with C4 null phenotypes and with HLA B35 and DR4. Studies of plasma proteins in HSP patients show an increased IgA concentration, activation of the alternative pathway of complement and consumption of factor XIII. High molecular weight (polymeric) IgA has been detected in affected individuals, which some investigators have called "immune complexes". Many patients synthesise an IgA rheumatoid factor in the acute phase, but other autoantibodies are largely absent. In vitro studies of lymphocytes from HSP patients have demonstrated an increased number of IgA-bearing and secreting B cells, with altered T-cell regulation of antibody synthesis. While these observations point to immune dysregulation--primarily of IgA production--as a consistent feature of acute HSP, there is as yet insufficient information available to allow a consistent theory of pathogenesis to be formulated. PMID- 2242324 TI - Alport syndrome, basement membranes and collagen. AB - Alport syndrome, an inherited disorder of the kidney, eye and ear, has fascinated nephrologists, pathologists, and geneticists for nearly a century. With the recent application of molecular biochemical and genetic techniques, this mysterious disease has begun to yield some of its secrets. Alport syndrome can now be viewed as a generalized disorder of basement membranes that appears to result from mutations in an X-chromosome-encoded basement membrane collagen chain. This chain, along with two other novel collagen chains, is absent from Alport basement membranes, in contrast to the classical chains of collagen IV. Phenotypic heterogeneity in Alport syndrome probably arises from allelic mutations at a single genetic locus. The phenomenon of post-transplant anti glomerular basement membrane nephritis may be a manifestation of specific mutations at the Alport locus that prevent synthesis of the gene's protein product and the establishment of immunological tolerance. PMID- 2242328 TI - Nephrosis, peritonitis and complement deficiency. PMID- 2242329 TI - Increased incidence of haemolytic uraemic syndrome in children who have a father who is either a physician or a lawyer. PMID- 2242330 TI - Intravenous methylprednisolone. PMID- 2242331 TI - Clinical quiz. Asphyxiating thoracic dystrophy (Jeune syndrome). PMID- 2242332 TI - Brain amino acid levels in audiogenic seizure-susceptible rats following habituation to the auditory stimulus. AB - Hippocampic and brain stem levels of amino acids were determined in audiogenic seizure-susceptible rats following habituation by repeated exposure to the acoustic stimulus. The biochemical determinations were performed in the brains of 42 habituated animals and 23 not habituated seizure susceptible rats used as controls. It was found that the habituation process is associated with: a) increased levels of aspartate in hippocampus and pons; b) significantly decreased levels of glycine in the hippocampus and pons; c) decreased concentration of glutamate in the pons; d) no significant changes in the GABA concentrations in hippocampus and brain stem. The changes of the excitatory and inhibitory amino acids in the brain of the habituated rats cannot explain the fall in epileptic susceptibility associated with habituation. PMID- 2242333 TI - Parasomnias (non-epileptic nocturnal episodic manifestations) in patients with magnesium deficiency. AB - Twenty seven patients with parasomnias (night terrors, nocturnal motor automatisms, nocturnal verbal automatisms and sometimes with bruxisms) associated with magnesium deficiency were selected. In all of them marked hypomagnesemia, clinical, EEG and EMG signs of spasmophilic syndromes were found. The 8 hours polysomnographical recordings of all cases (monitored in a system with infra-red video-TV cameras) showed severe sleep disorders and EEG nocturnal abnormalities occurring in the SWS (especially in the I b, II and III stages) with disappearance in the REM sleep. The authors suggest that these clinical and polysomnographic anomalies may be the expression of the brain damage caused by magnesium deficiency or of the clinical electrographic manifestations of the reticulate neuronal hypersynchrony exacerbated by sleep. PMID- 2242327 TI - The pathophysiology of Sandimmune (cyclosporine) in man and animals. AB - Part I: The side-effects of Sandimmune that have been of most significance clinically are renal dysfunction, renal vascular damage and arterial hypertension. To examine the nature and the origin of such effects, the actions of Sandimmune on the renal tubule, the renal vessels and systemic vessels have been analyzed. To evaluate whether common vasoconstrictory systems may be involved, changes in the renin-angiotensin-aldosterone system and prostaglandin thromboxane system have been assessed. Comparison between animal and human data obtained in vivo and in vitro shows the actions of Sandimmune on the renal tubule to be modest and involve only a few specific effects. The major action of Sandimmune is on the vessels, vasoconstriction being the major cause of renal dysfunction and also the cause of arterial hypertension. Neither the circulating renin-angiotension-aldosterone system nor the prostaglandin-thromboxane system is clearly responsible for vasoconstriction. Although not itself a vasoconstrictor, Sandimmune seems to modulate the constrictory and dilatory response to other agents in several vascular beds. PMID- 2242334 TI - Alterations in brain-stem auditory responses induced by head down tilting in hypertensives with supine brain-stem disorders. AB - The influence of head down (HD) tilting on brain-stem auditory evoked responses (BAER) was studied in hypertensives with supine brain-stem disorders (occipital headache, vertigo, nausea, diplopia, blurred vision occurring after night recumbency), in hypertensives without such phenomena and in normotensives. In the latter two categories of subjects HD tilting had no effect on BAER. On the contrary, in hypertensives with supine brain-stem disorders the manoeuvre induced a constant prolongation of I-V and III-V intervals and a depression in the amplitude of wave V; the alterations of BAER produced by HD tilting reveal probably a dysfunction of the superior brain-stem area and might be due to the impaired cerebral venous draining subsequent to the manoeuvre. The study of BAER after HD tilting seems to be a proper means to attest the supine brain-stem disorders displayed by some hypertensives. PMID- 2242335 TI - Fibronectin. PMID- 2242336 TI - Spectral analysis of Doppler signal in the prophylaxis of ischemic cerebrovascular accidents in extra- and/or intracranial carotid and vertebral systems. AB - Using continuous-wave spectral analysis of Doppler signal (SADS) and/or pulsed wave transcranial Doppler ultrasonography (TCD-US) we examined 263 patients with ischemic cerebrovascular diseases (ICVD) symptoms in the carotid and vertebrobasilar (V-B) systems. The degree of stenosis was established by taking into consideration the parameters of the spectrum of frequency (systolic peak velocity--SV; end-diastolic velocity--DV); the ratio between SV of internal carotid artery (ICA) and common carotid artery (CCA); the ratio between DV of ICA and CCA as well as the value of the spectral broadening (SB) index. The diminution of DV in CCA with increased values of Pourcelot's circulatory resistance index (RP) and spectral broadening index (SB) as compared with the controlateral part, but with apparent increase (over 3.5 kHz) of SV in ICA was constantly observed in significant stenoses of extracranial ICA. Our observations have pointed out that when proximal ICA occlusion is being formed slowly and progressively, ECA (whose increased circulatory resistance under normal conditions reflects diminished diastolic velocities) gradually takes over the hemodynamic characteristics of ICA which is expressed by increased DV, approximating DV and ICA. This situation may give rise to erroneous interpretations. PMID- 2242337 TI - Children aged 10-17 of endogenous unipolar depressive parents and of normal parents. I. Psychopathology rate and relationship of the severity of the psychopathology to familial and environmental variables. AB - Seventy two children aged 10-17 of 42 endogenous unipolar depressive parents (proband children) and 72 children aged 10-17 of 66 normal parental couples (control children) were studied. Overall rate of psychopathology (disorders present at the time of investigation and one year before) reached 51% in proband children and 29% in control children. Depressive disorder rate reached 10% in proband children and 4% in control children. The sex of the depressive parent did not influence the psychopathology rate in offspring, while the early age of onset of the illness (under 30 years) in parent increased the psychopathology risk in children. The severity of the psychopathology in children defined as functional impairment was significantly dependent on the severity of the depressive illness in proband parent, the presence of psychopathology in the spouse of the depressive parent, the presence of psychopathology in the relatives of both parents, the socio-cultural level of the family and the violence expressed in the familial atmosphere. PMID- 2242338 TI - Granulomatous angiitis of the central nervous system. Case report. PMID- 2242340 TI - Proceedings of the 246th meeting of the Netherlands Society for Dermatology and Venereology. Rotterdam, 3 June 1989. PMID- 2242339 TI - Complex neuroradiologic diagnosis in unilateral exophthalmos. AB - This is a comparative study concerning diagnosis in unilateral exophthalmos. It was carried out in 40 patients admitted to the Neurosurgery Clinic of the "Gh. Marinescu" Hospital in Bucharest during 1986-1987. The patients were submitted to CT scan and other radiologic examinations with and without contrast media in order to improve reference to the neuroradiologic laboratory and increase the accuracy of the etiopathogenic diagnosis. PMID- 2242341 TI - Polyamine involvement in basal and estradiol-stimulated insulin-like growth factor I secretion and action in breast cancer cells in culture. AB - Recent evidence indicates that the polyamine pathway may play a significant role in the autocrine/paracrine control of breast cancer cell proliferation by hormones. To directly test this hypothesis, in the present experiments, we evaluated the polyamine involvement in immunoactive insulin-like growth factor I (IGF-I) secretion and IGF-I action using MCF-7 breast cancer cells cultured in serum-free medium in the presence and absence of estradiol (E2). Administration of the polyamine biosynthetic inhibitor, alpha-difluoromethylornithine (DFMO) induced a marked suppression of cellular ornithine decarboxylase (ODC) activity and polyamine levels which was associated with significant, although partial, inhibition of E2-stimulated growth. Exogenous putrescine administration repleted cellular polyamine pools and completely reversed the growth-inhibitory effect of DFMO. Despite these parallel changes in polyamine levels and proliferative activity, basal as well as E2-stimulated levels of immunoactive IGF-I measured in the conditioned media were unaffected by DFMO with and without exogenous putrescine administration. On the other hand, induction of polyamine depletion and repletion by the same treatments significantly (although partially) affected the proliferative action of exogenously added IGF-I. These findings indicate that polyamines, while not involved in immunoactive IGF-I production, play an important role, at least in part, in IGF-I action in this experimental system. Furthermore, we observed that the administration of a monoclonal antibody directed against IGF-I was able to partially block basal as well as of a monoclonal antibody directed against IGF-I was able to partially block basal as well as E2-stimulated MCF-7 cell proliferation. We conclude that immunoactive IGF I is an important but not sole mediator of MCF-7 breast cancer growth under our experimental conditions. The polyamine pathway plays an important role in the expression of its proliferative action. PMID- 2242342 TI - Characteristics of glucocorticoid-binding by inflammatory tissue of rats. AB - Glucocorticoid-binding activities of the granuloma cytosol were compared with those of the liver cytosol and of the serum in vitro. The granuloma cytosol bound cortisol (HC) about 4-fold higher than dexamethasone (DX) and triamcinolone acetonide (TA); the liver cytosol bound these two synthetic agonists more than HC. The kinetic parameters of the glucocorticoid-binding components of the granuloma and the liver cytosols were studied by the Scatchard method. The binding components of the granuloma cytosol had a single class of binding sites with high affinity for these three steroids, whereas the binding site of the liver cytosol had negative cooperativity or consisted of two distinct classes, because its Scatchard plot showed a hyperbolic curve. The granuloma glucocorticoid-binding components will be protein since their binding was prevented by a trypsin treatment and completely lost by heating at 60 C for 5 min. Heating at 25 or 37 degrees C for 30 min did not affect the HC-binding activity of the granuloma cytosol, regardless of prelabeling with the steroid. The binding activity for DX and TA were heat-labile and completely lost by heating the cytosol at 37 degrees C for 30 min without the respective steroid. The results of thermal inactivation and ammonium sulfate fractionation show the granuloma HC-binding protein closely resembles corticosteroid-binding globulin (CBG). From enzymatic determination of hemoglobin in tissue cytosols, attribution of the contaminating blood to the HC-binding activity of the cytosol is considered to be negligible. PMID- 2242343 TI - Localization and regulation of estrogen, progestin and androgen receptors in the seminal vesicle of the rhesus monkey. AB - We have used monoclonal antibodies against the estrogen (E), progestin (P) and androgen (A) receptors (R) to study receptor localization and regulation in the seminal vesicles of rhesus monkeys under different hormonal conditions. The antibodies caused substantial shifts of the appropriately labeled receptors on sucrose gradients. ER levels were lower in intact males than in immature, castrate, and estrogen-treated castrates. With immunocytochemistry, ER were detectable only in stromal and smooth muscle cells, not the epithelium. The number of ER-positive stromal cells was significantly lower in intact males than in immature, castrate, and estrogen-treated castrates, and low in a DHT-treated castrate animal. Androgen receptors were localized in epithelial as well as stromal and smooth muscle cells, and the number of AR-positive stromal cells was highest in intact adults and lowest in castrated and immature animals. Estrogen treatment at the time of castration induced PR in the ER-positive stromal cells, prevented a decline in the number of AR-positive stromal cells, and caused stromal hypertrophy. In summary, in the seminal vesicle, as in the prostate, ER is restricted to the fibromuscular stroma, is suppressed by androgens, and can mediate induction of PR on estrogen treatment. Androgen receptors are present in epithelial as well as stromal and smooth muscle cells, but variations in hormonal state appear to affect regulation of AR more in the stroma than the epithelium. PMID- 2242344 TI - Metabolism of progesterone by avian granulosa cells in culture. AB - Previous studies have demonstrated that progesterone is the primary product of steroidogenesis in avian granulosa cells during short-term incubation. However, during more prolonged culture, lasting several days, the progesterone content in the medium was found to decrease progressively, indicating in vitro metabolic conversion. In the present study we have isolated and identified a number of progesterone metabolites. Granulosa cells, isolated from mature ovarian follicles of laying hens, were cultured in medium 199 supplemented with fetal calf serum and containing [14C]progesterone. After 4 days in culture, cells + media were extracted and the radioactive metabolites separated and identified by TLC, HPLC and GC-MS. Several of the metabolites were further characterized by derivatization and crystallization to constant specific activity. A total of 24 radioactive substances was detected. Of these, 15 have been positively identified, 5 tentatively and the remaining 4 are unidentified. The principal metabolite, representing more than 45% of the total radioactivity, was identified as 3 alpha-hydroxy-5 beta-pregnan-20-one. In addition, significant amounts of 3 alpha-hydroxy-5 alpha-pregnan-20-one (5.76%), 5 beta-pregnane-3,20-dione (3.05%), and 5 alpha-pregnane-3,20-dione (2.95%) were detected and identified. The results indicate that avian granulosa cells possess 3 alpha-hydroxy-steroid dehydrogenase (3 alpha-HSD), 17 beta-HSD, 20 alpha-HSD, 20 beta-HSD, 17 alpha-hydroxylase, C17 20-lyase and 5 alpha- and 5 beta-reductase activities. These enzyme activities may convert progesterone to biologically inactive or less active metabolites. However, a functional role for some of these metabolites cannot be ruled out. PMID- 2242345 TI - Side-chain cleavage of cholesterol sulfate by ovarian mitochondria. AB - Mitochondria isolated from porcine corpora lutea and from the luteinized ovaries of gonadotropin-treated immature rats were found to efficiently cleave the side chain of cholesterol sulfate to produce 3 beta-hydroxy-5-pregnen-20-one sulfate (pregnenolone sulfate). When mitochondria were preincubated with cholesterol sulfate, the time-course for the side-chain cleavage of cholesterol sulfate was biphasic. With 200 microM cholesterol sulphate, the initial rate of the reaction was the same as that observed for 25-hydroxycholesterol. This rate was not increased when both cholesterol sulfate and 25-hydroxycholesterol were incubated together. The rate of side-chain cleavage by isolated mitochondria supplied with 75 microM cholesterol sulfate as substrate was inhibited by 97% by aminoglutethimide, a specific inhibitor of cytochrome P-450scc. The slow phase of side-chain cleavage of cholesterol sulfate appeared to be limited by the rate of substrate movement to the mitochondrial site of the reaction. Cholesterol sulfate translocation rates were however up to 8 times greater than those observed for cholesterol when equivalent concentrations of the two substrates were added to the mitochondria. We conclude that cholesterol sulfate is a better substrate than cholesterol for side-chain cleavage by isolated mitochondria and that both reactions are catalysed by the same cytochrome P-450scc enzyme. PMID- 2242346 TI - Androstenedione is an important precursor of dihydrotestosterone in the genital skin of women and is metabolized via 5 alpha-androstanedione. AB - Androgen action is largely determined by the formation of dihydrotestosterone in target tissues. In women, androstenedione is the major precursor of dihydrotestosterone production in female genital skin. The present study was initiated to determine whether androstenedione is converted to dihydrotestosterone primarily via testosterone or 5 alpha-androstane-3,17-dione (5 alpha-androstanedione), and to examine the pathway of androstenedione metabolism in genital skin. Genital skin was obtained from 9 normal premenopausal women and 2 normal men. Each tissue was incubated with [3H]androstenedione in RPMI-1640 medium for 1 h at 37 degrees C in 95% O2/5% CO2. The metabolites were separated and purified by paper partition and thin-layer chromatography. The conversions of androstenedione to 5 alpha-androstanedione and to androsterone were similar (10.45 +/- 1.46 and 11.04 +/- 2.04%/200 mg tissue), and were approx. 12, 8 and 23 times higher than the conversion of androstenedione to testosterone, dihydrotestosterone and 5 alpha-androstane-3 alpha,17 beta-diol, respectively. The male samples showed a similar pattern of metabolism. These data indicate that 5 alpha-androstanedione is the most important intermediate in the conversion of androstenedione to dihydrotestosterone. The data also confirm the importance of 5 alpha-reductase activity over that of 17 beta-hydroxysteroid oxidoreductase activity in the expression of androgen action in women. PMID- 2242347 TI - Adrenal P-450scc catalyzes deoxycorticosterone 6 beta-hydroxylase reaction. AB - Purified bovine P-450scc, the cholesterol side-chain cleaving P-450 in adrenal cortex mitochondria, was found to catalyze a deoxycorticosterone 6 beta hydroxylase reaction. A turnover number (moles of product formed/min/mol of P 450) of 12 was found similar to that for cholesterol side chain cleavage activity. Conversion was dose-dependent in terms of P-450scc and no reaction took place when any one of the required electron donating components such as NADPH, NADPH-adrenodoxin reductase, or adrenodoxin was omitted. These results confirm and extend earlier observations that 21-hydroxypregnenolone is transformed into both deoxycorticosterone and 6 beta-hydroxydeoxycorticosterone by incubation of adrenal gland slices. PMID- 2242348 TI - Studies on anabolic steroids--4. Identification of new urinary metabolites of methenolone acetate (Primobolan) in human by gas chromatography/mass spectrometry. AB - The metabolism of methenolone acetate (17 beta-acetoxy-1-methyl-5 alpha-androst-1 en-3-one), a synthetic anabolic steroid, has been investigated in man. After oral administration of a 50 mg dose of the steroid to two male volunteers, twelve metabolites were detected in urine either in the glucuronide, sulfate or free steroid fractions. Methenolone, the parent steroid was detected in urine until 90 h after administration. Its cumulative urinary excretion accounted for 1.63% of the ingested dose. With the exception of 3 alpha-hydroxy-1-methylen-5 alpha androstan-17-one, the major biotransformation product of methonolone acetate, metabolites were excreted in urine at lower levels, through minor metabolic routes. Most of methenolone acetate metabolites were isolated from the glucuronic acid fraction, namely methenolone, 3 alpha-hydroxy-1-methylen-5 alpha-androstan 17-one, 3 alpha-hydroxy-1 alpha-methyl-5 alpha-androstan-17-one, 17 epimethenolone, 3 alpha,6 beta-dihydroxy-1-methylen-5 alpha-androstan-17-one, 2 xi-hydroxy-1-methylen-5 alpha-androstan-3,17-dione, 6 beta-hydroxy-1-methyl-5 alpha-androst-1-en-3,17-dione, 16 alpha-hydroxy-1-methyl-5 alpha-androst-1-en 3,17-dione and 3 alpha,16 alpha-dihydroxy-1-methyl-5 alpha-androst-1-en-17-one. Interestingly, the metabolites detected in the sulfate fraction were isomeric steroids bearing a 16 alpha- or a 16 beta-hydroxyl group, whereas 1-methyl-5 alpha-androst-1-en-3,17-dione was the sole metabolite isolated from the free steroid fraction. Steroids identity was assigned on the basis of the mass spectral features of their TMS ether, TMS enol-TMS ether, MO-TMS, and d9-TMS ether derivatives and by comparison with reference and structurally related steroids. The data indicated that methenolone acetate was metabolized into several compounds resulting from oxidation of the 17-hydroxyl group and reduction of A-ring substituents, with or without concomitant hydroxylation at the C6 and C16 positions. PMID- 2242349 TI - Growth stimulation by androgens, glucocorticoids or fibroblast growth factors and the blocking of the stimulated growth by antibody against basic fibroblast growth factor in protein-free culture of Shionogi carcinoma 115 cells. AB - Shionogi carcinoma 115 (SC115) has been accepted for 20 years as an androgen responsive mouse mammary tumor. We have established an androgen-dependent cloned cell line (SC-3) from a SC115 tumor. In a serum-free medium, testosterone (T) or fibroblast growth factors (FGFs) markedly stimulate the growth of SC-3 cells, and the T-induced growth was shown to be mediated through FGF-like peptide(s) in an autocrine mechanism. Since we used the serum-free culture including 0.1% bovine serum albumin (BSA), a partially serum-containing condition, putative roles of BSA- or serum-borne growth factors in growth stimulation of autocrine production of FGF-like peptide(s) could not be excluded. This paper reports findings performed in a protein-free medium including plating [Ham's F-12:MEM (1:1; v/v)]. In the protein-free culture, the growth of SC-3 cells was significantly stimulated by the addition of greater than or equal to 10(-10) M T (up to 20 fold), greater than or equal to 10(-7) M dexamethasone (Dex; up to 7-fold) or greater than or equal to 1 ng/ml basic (b) or acidic FGF (up to 10-fold); other various growth factors had no such effects. Furthermore, DNA synthesis of SC-3 cells induced by T, Dex or bFGF was similarly and markedly inhibited by bFGF neutralizing antibody IgG. Therefore, the present findings seem to demonstrate that androgens or high levels of glucocorticoids induce the production and secretion of FGF-like peptide(s) from SC-3 cells for their growth even in the absence of additional support by other factors. PMID- 2242350 TI - Impaired development of mammary glands in scorbutic rats unable to synthesize ascorbic acid. AB - The effects of ascorbic acid (AsA)-deficiency on the development of mammary glands were investigated using mutant rats (osteogenic disorder syndrome rats; ODS rats) with hereditary inability to synthesize AsA. Female ODS rats of 21 days old were castrated and divided into two groups. One group was given AsA in their drinking water, and the other was not. All the rats received a daily injection of oestradiol-17 beta and progesterone (EP) from day 28 to day 49 of age. After EP treatment, the concentrations of AsA in the mammary glands of rats not given AsA were less than one tenth of those of rats given AsA and the contents of hydroxyproline in the mammary glands of the former rats were about half of those in the latter. Furthermore, the concentration of serum prolactin in rats not given AsA was reduced to about one third of that in rats given AsA. After EP treatment, whole mounts of mammary glands showed that in rats not given AsA the development of ducts was impaired and there was extensive accumulation of endbuds. Consistent with this finding, EP injections did not increase the area of parenchyma in the mammary glands of rats not given AsA, whereas they increased it about 2-fold in rats given AsA. Moreover, after EP treatment the amount of alpha lactalbumin was significantly less in the mammary parenchyma of rats not given AsA than in that of rats given AsA. On the other hand, AsA deficiency did not impair the response of the mammary cells to insulin or prolactin in terms of DNA synthesis and alpha-lactalbumin production. These findings indicate that AsA deficiency impaired the development of mammary glands. This effect may be partly attributable to a defect in collagen synthesis in the mammary glands and a decrease in the concentration of serum prolactin. PMID- 2242352 TI - Cytochrome P-450scc-catalyzed production of progesterone from 22R-hydroxycholest 4-en-3-one by way of 20,22-dihydroxycholest-4-en-3-one. AB - Transient accumulation of a dihydroxylated steroid was found when 22R hydroxycholest-4-en-3-one was used as the substrate for a reconstituted cholesterol side-chain cleavage system derived from bovine adrenocortical mitochondria. The indications were that the accumulated steroid was an intermediate in the cytochrome P-450scc-catalyzed reaction. The retention time of the accumulated intermediate was identical with that of authentic 20,22 dihydroxycholest-4-en-3-one on HPLC. When 22R-hydroxycholesterol and 22R hydroxycholest-4-en-3-one were incubated simultaneously, the total amount of reaction products was essentially the same as that observed with 22R hydroxycholest-4-en-3-one alone. Under the conditions employed, the apparent turnover number of cytochrome P-450scc for 22R-hydroxycholesterol was calculated to be 77 nmol/min/nmol P-450 from the amount of pregnenolone formed, whereas the apparent turnover number for 22R-hydroxycholest-4-en-3-one was 64 nmol/min/nmol P 450 with respect to the intermediate formation and 77 nmol/min/nmol P-450 with respect to the progesterone formation. The apparent turnover number for 20,22 dihydroxycholest-4-en-3-one was about 125 nmol/min/nmol P-450, which was not significantly different from that of 20,22-dihydroxycholesterol. The apparent Km for 22R-hydroxycholesterol was about 20 microM and those for 22R-hydroxycholest-4 en-3-one and 20,22-dihydroxycholest-4-en-3-one were 50 and 40 microM, respectively. Thus, 22R-hydroxycholest-4-en-3-one was efficiently metabolized to progesterone by way of 20,22-dihydroxycholest-4-en-3-one by cytochrome P-450scc. PMID- 2242351 TI - Antibodies against synthetic peptides recognize the human and rat androgen receptor. AB - Antibodies against two synthetic peptides (aa 299-311 and aa 544-559) selected in different immunogenic domains of the human AR, were induced in rabbits. Antiserum reactivity against the native receptor was investigated by gel permeation chromatography and sucrose density gradient centrifugation using [3H]mibolerone labeled rat prostate cytosol and [3H]5 alpha-dihydrotestosterone-labeled T-47D cytosol as a source of AR. The absence of cross-reactivity of the antisera with estrogen, progesterone and glucocorticoid receptor was confirmed by density gradient centrifugation of rat uterus cytosol labeled with [3H]E2 or [3H]ORG 2058 and rat liver cytosol labeled with [3H]dexamethasone. After partial proteolytic breakdown of rat prostate AR by endogenous proteases the steroid-labeled receptor was recognized only by the second peptide (aa 544-559) antibody. This proteolytic breakdown could be prevented to a large degree by addition of a high concentration of soybean trypsin inhibitor. The specific AR antibodies provide new tools for the functional analysis of AR, since they interact selectively with specific domains of the receptor. PMID- 2242353 TI - Anabolic steroid effects on immune function: differences between analogues. AB - As an untoward effect of chronic anabolic steroid use, immunologic alterations may be induced. To evaluate this possibility five commercially available steroids with various types of structural differences were studied in male Sprague-Dawley rats. Animals were divided into five groups and treated with testosterone (Group 1), testosterone propionate (Group 2), testolactone (Group 3), oxandrolone (Group 4), and stanozolol (Group 5). Androgenic anabolic steroids were administered daily, subcutaneously dissolved in oil, at a dose of 1.1 mg/kg. Immune alterations were assessed by skin-test responses to phytohemagglutinin. After five days of treatment (1.1 mg/kg/day) a significant immuno-suppression was observed with all groups. However, by day 10, groups 3, 4, and 5 showed an immuno stimulation. Using oxandrolone as the model stimulant, serum testosterone levels were significantly suppressed, while castration abolished the stimulatory effect. These observations indicate that immune alterations do occur with anabolic steroids which are immuno-suppressive when the steroid nucleus is intact and immuno-stimulatory with nuclear alterations. It appears that these changes are associated with altered gonadal testosterone release. PMID- 2242354 TI - In vivo evaluation of 7 alpha-[11-(4-[125I]iodophenoxy)undecyl]-17 beta estradiol: a potential vector for therapy of adrenal and estrogen receptor positive cancers. AB - 7 alpha-[11-(4-[125I]Iodophenoxy)undecyl]-17 beta-estradiol ([125I]IPUE2) was synthesized and its tissue distribution studied in immature female Fischer rats. Upon intravenous administration, [125I]IPUE2 was shown to accumulate in the adrenals and, to some extent, in the uterus and the ovaries. Coinjection with estrogen receptor (ER)-saturating quantities of unlabeled 17 beta-estradiol did not significantly reduce the uptake of [125I]IPUE2 in these tissues. The high adrenal uptake of [125I]IPUE2 is most likely associated with the lipophilic nature of the 7 alpha-substituted estradiol. The potential to use the 7 alpha undecylestradiol as a vector to direct therapeutic groups to adrenal and ER positive cancers is discussed. PMID- 2242355 TI - Sexual dimorphism characterizes baboon myocardial androgen receptors but not myocardial estrogen and progesterone receptors. AB - Using biochemical methods we established that estrogen receptor content and distribution and progesterone receptor content in female and male baboon myocardium did not differ between sexes. In contrast, myocardial androgen receptor distribution between cytosolic and nuclear compartments was sexually dimorphic. Female baboon myocardial androgen receptors were restricted to the cytosolic compartment, whereas male myocardial androgen receptors were distributed between the cytosolic and nuclear compartments. Using human estrogen receptor cDNA we showed that baboon aorta, myocardium and uterus contain a 6.3 kb estrogen receptor transcript. Analyses performed with human progesterone receptor cDNA established that baboon aorta and uterus contain an 8 kb progesterone receptor transcript; however, progesterone receptor transcripts were not demonstrable in baboon myocardial RNA preparations. Because relative hybridization signal intensity reflected known uterine and aortic progesterone receptor content, failure to detect progesterone receptor transcripts in myocardial preparations may reflect sensitivity limitations and the fact that aortic progesterone receptor content is 5-fold greater than that of myocardium. Immunocytochemical analyses demonstrated that baboon myocardial progesterone receptors were present in greater than 25% of myocytes and generally absent from other myocardial cells. Our studies establish that: (1) gonadal steroid hormone receptor gene transcription occurs in cells of the baboon cardiovasculature, (2) these steroid hormone receptors may be physiologically functional, and (3) gonadal steroid hormone receptors may be restricted to specialized cells of the cardiovasculature. PMID- 2242356 TI - Antiprogestagenic inhibition of uterine prostaglandin inactivation: a permissive mechanism for uterine stimulation. AB - The use of antiprogestins as abortifacients is more effective when antiprogestin priming is followed by the administration of a small dose of synthetic prostaglandin. This increased myometrial sensitivity towards PG has not been explained and experiments in the guinea-pig where no myometrial activity is observed after 48 h of antiprogestin administration together with measurements of PG metabolites in uterine vein blood have given rise to the suggestion that prostaglandin synthesis is inhibited by antiprogestins. We have treated groups of 50 day pregnant guinea-pigs with 10 mg RU486 or vehicle alone and examined the ability of homogenised uterine tissues (myometrium/decidua, cervix, chorion and amnion) to metabolize PGE when given a large excess of substrate and sufficient cofactors. In addition we have examined the ability of these homogenates to synthesis PG. Antiprogestin treatment in vivo resulted in a 9-fold reduction in metabolic activity in chorion (P less than 0.02) and a 4-fold reduction in myometrium/decidua (P less than 0.02). Reduction in activity seen in amnion and cervix was not significant. The maximum metabolism was seen in the chorion and minimal metabolism in the amnion. Maximum PG production was seen in the amnion and minimum in the chorion. These results show that the effect of antiprogestin in reducing prostaglandin catabolism would reduce the threshold above which PG production would cause contractions which would in turn stimulate PG production. Thus an explanation is provided of how low doses of exogenous PGs or transient synthesis of endogenous PG within an antiprogestin treated uterus can led to a self sustaining cycle of stimulation which will lead to abortion. PMID- 2242358 TI - Pain relief in labour. PMID- 2242357 TI - Annual meeting of the American Society of Regional Anesthesia. Orlando, Florida, March 25-28, 1990. Abstracts. PMID- 2242359 TI - Perinatal bereavement. PMID- 2242360 TI - Genetic and familial predisposition to eclampsia and pre-eclampsia in a defined population. AB - Familial predisposition and patterns of genetic inheritance of eclampsia and pre eclampsia were investigated through three or four generations in 94 families from the homogenous island population of Iceland. The families descended from index women delivered in the years 1931-47 and who had either eclampsia (n = 38) or severe pre-eclampsia (n = 69). Inheritance was followed both through sons and daughters. The prevalence of pre-eclampsia and eclampsia in daughters was significantly higher (23%) than that in daughters-in-law (10%). No difference was noted in the prevalence of these diseases by whether the daughter was born of an eclamptic or pre-eclamptic mother or whether she was a first or later born daughter. There was a non-significantly higher occurrence of pre-eclampsia among grand-daughters than in grand-daughters-in-law. No difference was seen by whether grand-daughters descended through sons or daughters. With increasing numbers of affected daughters or grand-daughters the probability rose of finding more affected women in a family. Hypotheses of single recessive and dominant gene inheritance were compared and maximum likelihood estimates for gene frequency obtained. For a single recessive gene model this was 0.31 reflecting a population prevalence of 9.6%, whereas a dominant model with incomplete penetrance gave 0.14 at 48% gene penetrance, corresponding to a population prevalence of 0.9% homozygous expression of severe disease and 11% heterozygous expression of milder disease. Either genetic model could fit the data. PMID- 2242361 TI - Pelvic floor damage and childbirth: a neurophysiological study. AB - Ninety six nulliparous women were investigated to establish whether childbirth causes damage to the striated muscles and nerve supply of the pelvic floor. The techniques used were concentric needle electromyography (EMG), pudendal nerve conduction tests and assessment of pelvic floor contraction using a perineometer. There was EMG evidence of re-innervation in the pelvic floor muscles after vaginal delivery in 80% of those studied. Women who had a long active second stage of labour and heavier babies showed the most EMG evidence of nerve damage. Forceps delivery and perineal tears did not affect the degree of nerve damage seen. We conclude that vaginal delivery causes partial denervation of the pelvic floor (with consequent re-innervation) in most women having their first baby. In a few this is severe and is associated with urinary and faecal incontinence. For some it is likely to be the first step along a path leading to prolapse and/or stress incontinence. PMID- 2242362 TI - Epidemiology of pelvic inflammatory disease in parous women with special reference to intrauterine device use. AB - Up to the end of 1989, 206 parous women in the Oxford Family Planning Association contraceptive study had been referred to hospital with a first episode of pelvic inflammatory disease. Of these, 65 suffered from definite disease described as acute, 81 from definite disease not described as acute and 60 from 'other disease'. Considering all forms of disease together, referral was less common in those aged 25-29 and in those aged 45 or more than in those aged 30-44. Referral was more common in those of low social class, in those who smoked and in those who married young. All these factors were taken into account in analyses considering the effects of contraceptive methods. In these analyses, women currently using the contraceptive pill, the diaphragm, the sheath, female sterilization or an intrauterine device (IUCD) were compared with those currently using other methods or no method of contraception. IUCD ex-users were, however, placed in a separate category, irrespective of their current method of contraception. The relative risks obtained in these analyses, with 95% CI, were as follows: contraceptive pill 0.5 (0.2-0.9), diaphragm 0.6 (0.3-1.2), sheath 1.2 (0.6-2.4), female sterilization 0.7 (0.3-1.5), non-medicated IUCD 3.3 (2.3-5.0), medicated IUCD 1.8 (0.8-4.0), IUCD ex-users 1.3 (0.7-2.3). These data suggest that oral contraceptives, the diaphragm and female sterilization protect against pelvic inflammatory disease and that IUCDs increase the risk. Medicated devices, however, appear to carry only about half the risk of non-medicated devices, and the elevation of risks in IUCD ex-users appears to be small. Special analyses examined the risk associated with use of a Dalkon Shield. Among women currently using an IUCD (of any kind), those who had used a Dalkon Shield (at any time) had nearly five times as great a risk of hospital referral for pelvic inflammatory disease as those who had never used a Dalkon Shield (relative risk 4.7, 95% CI 2.1-9.0). PMID- 2242364 TI - Middle cerebral artery flow velocity waveforms in fetal hypoxaemia. AB - In 81 small-for-gestational age fetuses (SGA) colour flow imaging was used to identify the fetal middle cerebral artery for subsequent pulsed Doppler studies. Impedence to flow (pulsatility index; PI) was significantly lower, and mean blood velocity was significantly higher, than the respective reference ranges with gestation. Fetal blood sampling by cordocentesis was performed in all SGA fetuses and a significant quadratic relation was found between fetal hypoxaemia and the degree of reduction in the PI of FVWs from the fetal middle cerebral artery. Thus, maximum reduction in PI is reached when the fetal PO2 is 2-4 SD below the normal mean for gestation. When the oxygen deficit is greater there is a tendency for the PI to rise, and this presumably reflects the development of brain oedema. PMID- 2242363 TI - The use of obstetric analgesia in Sweden 1983-1986. AB - The use of obstetric analgesia was investigated in a Swedish population-based prospective study of 335,207 births, which represents almost all women who had vaginal deliveries in Sweden between 1983 and 1986. Lumbar epidural analgesia (EDA) was used in 16%, paracervical block (PCB) in 12%, pethidine or morphine in 49% and pudendal block in 62%. All four types of analgesia were much more commonly used by nulliparae than multiparae. Variables such as maternal age, smoking, nationality, relationship with the infant's father and gestational age had only moderate influence on the rates of different types of analgesia. EDA and PCB were more frequently used in larger than in smaller hospitals and in the daytime than at night. No such differences were found for pethidine or morphine, or pudendal block, which were administered routinely by midwives. PMID- 2242365 TI - Experience with a 'physiological' steroid replacement regimen for the establishment of a receptive endometrium in women with premature ovarian failure. AB - Eighteen women with a premature menopause underwent assessment of serial serum oestradiol (E2) and progesterone levels and endometrial histology and function. Patients received continuous transdermal E2, and progesterone either orally or vaginally for 14 days. Physiological levels of E2 were attained. Significantly higher levels of progesterone were achieved with vaginal progesterone (P less than 0.01). Endometrial biopsies obtained during E2 replacement demonstrated normal proliferative features. Expression of an oestrogen related antigen (ER-Ag) was localized in the cytoplasm of the epithelium. After 3 days of progesterone replacement the endometrium showed normal secretory features and expression of ER Ag in the stroma as well as in the glands. After 7 days of progesterone supplementation, vaginal administration produced a more consistent physiological appearance than oral administration. Thus transdermal E2 combined with vaginal progesterone is a highly satisfactory combination for establishing a physiological endometrium in women with premature ovarian failure. PMID- 2242366 TI - Reliability of colposcopy and directed punch biopsy. AB - A group of 118 women underwent laser cone biopsy. Data were collected routinely on proforma case notes and entered into a computerized database. The histology of the cone biopsies was compared with that of previous, colposcopically directed punch biopsies, with the cytology of smears taken in the clinic and with the colposcopic diagnosis. The punch biopsy had a 54% false negative rate and neither of the two microinvasive carcinomas biopsied in this way were detected by the biopsy. Ten of 24 women with negative punch biopsies had CIN III in the cone. When the punch biopsy showed CIN II or worse, the cone biopsy confirmed the presence of CIN in 86%. There was some evidence of false negative cone biopsies. The data suggest that management should not be based solely upon the punch biopsy result but should include consideration of the cytology and colposcopy findings. Excisional methods of treatment are more likely to reveal early invasion and adenocarcinoma-in-situ. PMID- 2242367 TI - Prediction of pregnancy-induced hypertensive disorders by angiotensin II sensitivity and supine pressor test. AB - An angiotensin II sensitivity test and a supine pressor test were done consecutively at 28 weeks gestation in 90 healthy, normotensive nulliparous women. None of the supine pressor tests was positive, applying the predefined threshold of a rise of 20 mmHg in diastolic blood pressure after rolling over; nine tests were positive using a corrected 9 mmHg cut-off level. Ten women had a positive angiotensin sensitivity test using a threshold of the effective pressor dose of 8 ng/kg/min; 22 women were positive using an effective pressor dose of less than or equal to 10 ng/kg/min. Later in pregnancy 12 women (13%) developed pregnancy-induced hypertensive disease (PIH). The specificity of both tests of predicting the development of PIH was about 90%. The sensitivity of the angiotensin sensitivity test at the 10 ng/kg/min level was 92%. Because of its low sensitivity of 25% the supine pressor test appears to have no value for the prediction of PIH. There was a significant positive association between angiotensin II refractoriness and birthweight. PMID- 2242368 TI - The management of primary fallopian tube carcinoma. AB - The outcome of 30 patients with primary fallopian tube carcinoma is described. Treatment varied over the 22 year period of accrual and included combinations of surgery, radiotherapy and chemotherapy. There was an apparent increase in stage at treatment with time which was probably related to more precise staging at laparotomy and the greater use of computerized tomography. The median survival for all patients was 28 months and the 5-year survival was 18%. Ten patients received postoperative chemotherapy for residual disease with an overall response rate of 80% and median progression-free and overall survival times of 14 and 21 months respectively. The pattern of relapse was similar to that seen in ovarian carcinoma, with all but one patient having the pelvis or abdomen as the main site of recurrence. Primary fallopian tube carcinoma has a response to treatment and a tumour biology similar to that of ovarian carcinoma. It is recommended that the management of this uncommon malignancy should continue to be along the lines of ovarian carcinoma, with initial treatment by cytoreductive surgery followed by chemotherapy or radiotherapy for residual disease. PMID- 2242370 TI - The rate of rise of corticotrophin releasing factor and endogenous digoxin-like immunoreactivity in normal and abnormal pregnancy. AB - Maternal plasma concentrations of corticotrophin releasing factor (CRF) and endogenous digoxin-like immunoreactivity (EDLI) were estimated in 80 normal and 88 abnormal pregnancies which were sampled sequentially from 24 weeks gestation to delivery. A slope was fitted for each woman's antenatal EDLI and CRF values, both of which rose significantly during gestation, and the mean of the slopes for the normal and abnormal groups for each value compared. There was no evidence of significant mean differences between groups for EDLI but there was evidence of a significant mean difference for CRF (P less than 0.05). After adjustment for other variables which may affect pregnancy outcome, the slopes for CRF were found not to be significantly related to outcome. PMID- 2242369 TI - Prostaglandin induced cervical ripening under tocolytic cover in primiparae: results of a double blind placebo controlled trial. AB - In a double blind trial, 60 nulliparae with a modified Bishop score of less than or equal to 5 requiring induction of labour, received either 8 mg of salbutamol or an identical placebo orally, 30 min before vaginal administration of 2 mg prostaglandin E2 gel. Women in the salbutamol group experienced less uterine activity over the subsequent 12 h compared with those given placebo, and fewer (35%) commenced labour compared with the placebo group (62%). However, the change in cervical score was significantly less in the salbutamol group (mean 3.0, SD 3.1) than that in the placebo group (mean 5.8, SD 3.2), and the prostaglandin treatment to delivery time in the salbutamol group (mean 26.1 h, SD 6.49) was significantly longer than that in the placebo group (mean 19.3 h, SD 7.95). The first stage of labour lasted greater than 10 h in 11 women in the salbutamol group compared with five in the placebo group. Side effects attributable to salbutamol occurred in 10% of the treated women but in none of their fetuses and fetal outcome was satisfactory and similar in both groups. Our findings show that salbutamol can suppress prostaglandin-induced uterine activity during cervical ripening, which could be an advantage in induction of labour where a planned delivery is preferred. However, the poorer outcome of labour in salbutamol treated women mitigates against this approach. PMID- 2242371 TI - Antepartum to postpartum changes in transcapillary fluid balance. AB - During the puerperium significant changes occur in the body volume homeostasis. In the present study the transcapillary fluid balance was examined antepartum in nine healthy women. The interstitial colloid osmotic pressure was measured by the 'wick' method, and interstitial hydrostatic pressure by the 'wick-in-needle' method in subcutaneous tissue on the thorax and at the ankle. From antepartum (gestational week 37-40) to postpartum (5th day), the following changes were observed: A significant increase in the colloid osmotic pressure both in plasma (mean 1.8 mmHg, P = 0.027) and in the interstitial fluid at the ankle (mean 2.9 mmHg, P = 0.008). Neither colloid osmotic pressure gradient (plasma interstitium), interstitial hydrostatic pressure, nor haemoglobin and haematocrit changed. The observed rise in the interstitial colloid osmotic pressure must be caused by mobilization of fluid from the interstitium, probably due to a reduced capillary hydrostatic pressure. The increase in plasma colloid osmotic pressure is most likely caused by an increased albumin synthesis and/or transport of interstitial proteins back to the vascular compartment. PMID- 2242372 TI - Dipalmitoylphosphatidylcholine (L-alpha-lecithin) stimulates prostaglandin E production in human amnion. AB - The effect of dipalmitoylphosphatidylcholine (DPPC, L-alpha-lecithin), a substance not containing arachidonic acid, on prostaglandin E (PGE) production of amniotic membrane was studied. DPPC (3.125-800 micrograms/ml) stimulated PGE production of amniotic membrane (150-200%), suggesting that lecithin, the major surfactant component, is directly involved in the mechanism of human parturition as a stimulator of PGE production. PMID- 2242373 TI - Vitamin B6 in the treatment of the premenstrual syndrome--a review. AB - A search of the literature yielded 12 controlled trials on vitamin B6 in the treatment of the premenstrual syndrome. These are discussed with emphasis on methodological aspects. A major drawback of the trials is the limited number of patients included. The existing evidence of positive effects of vitamin B6 is weak, and some well-designed trials with positive results would be needed to change this view. PMID- 2242374 TI - Bilateral squamous cell carcinoma of the ovary. Case report. PMID- 2242376 TI - Anxieties in women undergoing colposcopy. PMID- 2242375 TI - Serum ionized calcium and intact parathyroid hormone levels during pregnancy and postpartum. PMID- 2242377 TI - Antenatal attendance and fasting of pregnant Muslims during Ramadan. PMID- 2242378 TI - Neonatal thyrotrophin and mode of delivery. PMID- 2242380 TI - Hyperthyroidism results in increased glycolytic capacity in the rat heart. A 31P NMR study. AB - We have investigated the metabolic adaptations that occur in the thyroxine treated rat heart. Rats were made hyperthyroid by daily intra-peritoneal injections of thyroxine (35 micrograms/100 g body weight) over seven days. 31P NMR investigations of isolated glucose-perfused isometric hearts showed that thyroxine treatment caused an increase in Pi (from 4.9 mumols.(g dry wt.)-1 in control hearts to 11.7 mumols.(g dry wt.)-1 in hyperthyroid hearts), a decrease in phosphocreatine (from 36.5 mumols.(g dry wt.)-1 to 21.8 mumols.(g dry wt.)-1) with no change in ATP or ADP concentrations under the same conditions of cardiac work. The unidirectional exchange flux Pi----ATP was measured by saturation transfer NMR in hyperthyroid rat hearts. This exchange (which has been shown to contain a significant glycolytic component) increased by 2.2-fold in thyroxine treated hearts in comparison to control hearts (to 3.6 mumols.(g dry wt.)-1.s-1, from 1.6 mumols.(g dry wt.)-1.s-1). In parallel experiments, NMR analysis of extracts from hyperthyroid rat hearts showed significantly elevated levels of glucose 6-phosphate, and fructose 6-phosphate. Measurements of enzyme activities isolated from hyperthyroid and control tissue showed a 40% increase in phosphofructokinase activity. These data together with the increased concentration of Pi show that both glycolytic and glycogenolytic fluxes are increased in the hyperthyroid rat heart. This metabolic adaptation may be necessary to cope with the increased number and activity of Na+/K(+)-ATPase pumps that occur in response to thyroxine treatment. PMID- 2242379 TI - Topical anaesthesia with lidocaine-prilocaine cream for vulval biopsy. PMID- 2242382 TI - Intracellular Ca2+ storage organelles in non-muscle cells: heterogeneity and functional assignment. PMID- 2242381 TI - A model for computer simulation of P-glycoprotein and transmembrane delta pH mediated anthracycline transport in multidrug-resistant tumor cells. AB - Anthracycline resistance in multidrug-resistant (MDR) tumor cells is due in part to a reduced cellular drug accumulation. Using a simple kinetic model and numerical computer simulations, we have analyzed mathematically the following possible mechanisms controlling fluxes of the membrane permeable anthracyclines in MDR cells: (1) active outward transport via a specific drug transporter (P glycoprotein), (2) exocytotic drug export via the endosomal vesicle system, and (3) pH-gradients across the plasma membrane. Model calculations were based on morphometric and kinetic data previously presented in the literature for daunorubicin transport in wild-type Ehrlich ascites tumor cells (EHR2) and the corresponding daunorubicin (DNR)-resistant cell line EHR2/DNR+. The results confirm the possible importance of the cell-surface pH in controlling DNR accumulation in the cells. With P-glycoprotein as the main efflux pump, a catalytic constant of the protein greater than 40 mol DNR transported/mol protein per min is predicted by the model calculations. Changes in the drug binding affinity of P-glycoprotein (Km = 10(-9)-10(-6) M) is of little importance in influencing its effectiveness to reduce DNR accumulation, which could explain the broad substrate specificity of the MDR efflux pump system. The conditions to evaluate unidirectional fluxes of DNR across the plasma membrane in cells with active P-glycoprotein are defined. An efflux mechanism which relies solely on pH dependent drug trapping in a pH 5 endosomal compartment by a simple diffusion process followed by exocytosis, appears inadequate to account for the high rate of DNR efflux in EHR2/DNR+ cells. PMID- 2242383 TI - High-affinity binding of thyroid hormones to neuroblastoma plasma membranes. AB - The binding of thyroid hormones to isolated plasma membranes was studied in NB41A3 neuroblasts. Saturable binding of L-T3, D-T3 and L-T4 was observed. Binding was time-dependent, with equilibrium reached in less than 60 min and maximal binding occurring between pH 7.4 and 7. Saturation experiments demonstrated two classes of sites for L-T3: a high-affinity site with Ka 8.4 X 10(9) M-1 and a low-affinity site with Ka 7.3 X 10(6) M-1.L-T3 and D-T3 inhibited each other's binding, L-T3 being several-times more potent. Affinity labeling of isolated membranes with bromoacetylated thyroid hormones disclosed stereospecific binding to SDS-PAGE bands with approximate molecular masses of 27 kDa (preferentially labeled by BrAc-L-T3), 32 kDa (preferentially labeled by BrAc-D T3), and 48 and 87 kDa (preferentially labeled by BrAc-L-T4). Binding of BrAc-L T3 to the 27 kDa band accounted for 3.4% of total binding, was selectively inhibited by excess L-T3, and may be involved in intracellular transport of L-T3. PMID- 2242384 TI - Effects of alanine on insulin-secreting cells: patch-clamp and single cell intracellular Ca2+ measurements. AB - The effects of alanine, glucose and tolbutamide on insulin-secreting cells (RINm5F) have been investigated using patch-clamp and single cell intracellular Ca2+ measurements. When directly challenged with the amino acid L-alanine (2-10 mM) the cells underwent a sharp depolarization, which led to the generation of Ca2+ spike potentials and an increase in [Ca2+]i. The L-alanine-induced depolarization was associated with a net inward membrane current but no measurable change in the resistance of the cell. The latter effect was found to be in contrast to the actions of glucose (5-10 mM) and tolbutamide (100 microM), both of which depolarized cells and raised [Ca2+]i by an increase in the input resistance of the cell membrane, due to the closure of ATP-sensitive potassium channels. In the complete absence of external Na+ (by replacement with 140 mM NMDG+), L-alanine had no effects on either the membrane potential or [Ca2+]i. Similarly, replacing Na+ with NMDG+ in the continued presence of the amino acid resulted in a repolarization of the membrane and an attenuation of the L-alanine induced rise in [Ca2+]i. The Na+ channel blocker TTX (1-2 microM) had no effects on the alanine-evoked electrical activity. Exchange of the L-form of the amino acid with the D-stereoisomer had similar actions to those of removing external Na+, since D-alanine had no effects on the membrane potential or [Ca2+]i. The actions of L-alanine were also found to be mimicked by the N-methylated amino acid analogue methylamino isobutyric acid (MeAIB) (2-10 mM), suggesting that the A-type electrogenic amino acid cotransport system operates in the RINm5F insulin secreting cell line. PMID- 2242385 TI - Effect of phorbol myristate acetate on processing of formyl peptide receptors by human neutrophils. AB - We examined the effect of phorbol myristate acetate on the ability of human neutrophils to process formyl peptide receptors. The receptor was affinity labeled and its extracellular localization assessed over time, by cleavage of extracellular labeled receptor with papain. Neutrophils were capable of internalizing (and/or recycling) affinity labeled formyl peptide receptor in the absence of extracellular calcium. This phenomenon was dependent upon stimulation with phorbol myristate acetate, suggesting a role for protein kinase C in this process. PMID- 2242386 TI - Barium mimics the effect of D-glucose on 86Rb+ fluxes in mouse pancreatic beta cells. AB - The interaction between Ba2+, furosemide and D-glucose on 86Rb+ fluxes in ob/ob mouse islets was investigated. Ba2+ (2 mM) significantly reduced the ouabain resistant 86Rb+ influx, without affecting the ouabain-sensitive influx. D-Glucose (20 mM) reduced the 86Rb+ influx in the absence of Ba2+ (2 mM) but not in the presence of the cation. Furosemide, an inhibitor of Na+, K+, Cl- co-transport, reduced the 86Rb+ influx and the effect was partly additive to the effect of 2 mM Ba2+. When the islets were preincubated with Ba2+ (2 mM) the specific effect of 1 mM furosemide on the 86Rb+ influx was reduced, whereas, in acute experiments, Ba2+ (2 mM) did not affect the specific effect of furosemide on 86Rb+ influx. 86Rb+ efflux from preloaded islets was significantly reduced by 2 mM Ba2+ and during the first 5 min of ion efflux the effect of the combination of 2 mM Ba2+ and 1 mM furosemide was stronger than the effect of Ba2+ alone. The data show that Ba2+ reduces 86Rb+ fluxes in the beta-cells and suggest that this is mainly mediated by inhibition of K+ channels in the beta-cell plasma membrane. Long-term exposure to Ba2+ may also reduce the activity of the Na+, K+, Cl- co-transport system. The effect of Ba2+ on K+ channels may help to explain the stimulatory effect on insulin release in the absence of nutrient secretagogues. PMID- 2242387 TI - A pilot study of a neuroendocrine test battery in posttraumatic stress disorder. AB - Eight female patients who fulfilled DSM-III criteria for posttraumatic stress disorder (PTSD) took part in this study. They were each assessed using the dexamethasone suppression test, the desipramine/growth hormone stimulation test, which examines alpha-2-adrenoceptor functioning, and the buspirone/prolactin test, which is thought to examine 5-HT receptor functioning. A control group consisting of age- and sex-matched healthy subjects was also tested. For each subject the three tests were conducted over 5 days. Hormone assays were carried out blind to diagnosis. Overall no differences on any of the three tests were detected between the patients and controls. The results do not support a link between PTSD and major depression. PMID- 2242389 TI - A cross-sectional study of the effects of depression on REM latency. AB - In a cross-sectional design to address the effects of the course of depression on rapid-eye-movement (REM) latency, we have matched patients in their first-episode with (1) age-matched patients with recurrent depression, (2) onset-matched patients with recurrent depression, and (3) age-matched normal control subjects. Patients were also matched for sex and treatment site (inpatient or outpatient). No differences were found in REM latency for the three depressed groups, and all had lower REM latency than normals. This finding is taken as support for stable REM latency throughout the course of depression. PMID- 2242388 TI - Sleep, gender, and depression: an analysis of gender effects on the electroencephalographic sleep of 302 depressed outpatients. AB - Gender-related differences in electroencephalographic (EEG) sleep were examined in 151 pairs of men and women with major depression, all outpatients, matched for age and severity of depression. Across five decades (age 21-69), depressed men had less slow-wave sleep than did depressed women. Gender differences were small with respect to visually scored measures of slow-wave sleep time and percent, but moderate for gender differences in automated measures of slow-wave density. The time constant of the polygraph preamplifier significantly affected both visually scored and automatically scored slow-wave sleep. Other measures such as REM sleep latency, first REM period duration, sleep efficiency, and early morning awakening, showed robust age effects, but no main effects for gender or gender-by age interactions. Gender effects on slow-wave sleep and delta-wave counts in depression parallel gender effects seen in healthy aging. The possibility of occult alcohol use by depressed male outpatients cannot be definitely excluded as a partial explanation of the current findings. However, covarying for past alcohol abuse did not negate the statistical significance of the observed gender effects on slow-wave sleep and delta-wave density. The possibility of gender differences in slow-wave regulatory mechanisms is suggested, but similarity in temporal distribution of delta-wave density between the first and second non rapid-eye-movement (NREM) periods does not support gender differences in slow wave sleep regulation. PMID- 2242390 TI - Smooth pursuit eye movements of normal and schizophrenic subjects tracking an unpredictable target. AB - An experimental paradigm employed by several workers in the field of schizophrenic eye movements has involved finding sequences of stimuli that induce saccadic smooth pursuit in the eye movements of normal individuals. It is hoped that the identification of such stimuli will lead to clues concerning the etiology or nature of eye tracking dysfunction in schizophrenia. In this study, the pursuit eye movements of normal and schizophrenic subjects tracking an unpredictable target (composed of summed sine waves) were examined. Eye tracking performance was evaluated both qualitatively and quantitatively using percent root-mean-square (%RMS) error and pursuit gain scores. Schizophrenics are capable of tracking an unpredictable target. This finding has implications for our understanding of schizophrenic information processing during visual tracking. PMID- 2242391 TI - EEG and CT findings in patients with panic disorder. AB - Fifty-four patients with panic disorder were investigated using extensive electroencephalographic (EEG) recordings and computerized tomography (CT). Fifteen (28%) of these patients had previously been treated for temporal lobe epilepsy or were considered to have another neurological disorder. EEG recordings showed increased slow-wave activity in 13 (24%) patients and CT scan revealed incidental abnormalities in 6 (20%) of the 30 patients investigated. Taking into account the limitations of the methods applied, the present results indicate that clear-cut epileptic EEG patterns only rarely occur in panic disorder: the vast majority of panic patients exhibit normal EEG and CT findings. PMID- 2242392 TI - Chronic treatment with prolixin causes oxidative stress in rat brain. PMID- 2242393 TI - Polymers for biodegradable medical devices. V. Hydroxybutyrate-hydroxyvalerate copolymers: effects of polymer processing on hydrolytic degradation. AB - The effects of melt processing on those properties of polyhydroxybutyrate hydroxyvalerate copolymers that control hydrolytic stability were studied. Initial experiments using a non-thermal preparation technique enabled the relationship between initial molecular weight and rate of hydrolytic degradation to be established. This rate was conveniently expressed in terms of the time for 10% by weight of the sample to be eroded. By varying melt processing conditions, the range of effects of processing on sample molecular weight and molecular weight distribution were investigated. These effects were found to be quite dramatic, with a reduction to 50% of the initial molecular weight being readily achieved. Temperature, shear rate and dwell time interrelated to control the extent of thermal degradation achieved during processing. The principal effect of copolymer composition resulted from the fact that an increase in hydroxyvalerate content led to a reduction in melting point and enabled milder processing conditions to be used. Enhanced crystallinity, resulting from more favourable processing conditions reduced hydrolytic degradation rates. As a result, melt processing produced a complex interrelation of effects, all of which influenced the hydrolytic stability of the fabricated specimen. In general, molecular weight effects predominated. PMID- 2242394 TI - Surface properties of copolymers of alkyl methacrylates with methoxy (polyethylene oxide) methacrylates and their application as protein-resistant coatings. AB - New polymeric surfactants, copolymers of alkyl methacrylates with methoxy (polyethylene oxide) methacrylates, were synthesized and characterized by gel permeation chromatography. They were studied as possible means to produce polyethylene oxide-rich surfaces by a simple coating treatment on common hydrophobic medical materials. They were further studied as cleaners for the removal of proteins preadsorbed on hydrophobic surfaces. The surface properties of the copolymers such as the adsorption properties of the copolymer on a hydrophobic surface, low density polyethylene, the protein-resistant character of the prepared polyethylene oxide surfaces and the effectiveness of the copolymers for removal of proteins pre-adsorbed on the surface, were investigated by X-ray photoelectron spectroscopy and by using 125I-labelled copolymers and 125I labelled proteins. The surface properties of the synthesized copolymers were compared with those of commercially available polyethylene oxide containing block copolymer surfactants. PMID- 2242395 TI - Radiation-induced graft copolymerization of methacrylic acid on to poly(vinyl chloride) films and their thrombogenicity. AB - Methacrylic acid (MAA) was radiation grafted on to poly(vinyl chloride) (PVC) films to improve the blood compatibility of PVC. The thromobogenicity of MAA grafted PVC was evaluated by thrombus formation, platelet adhesion and haemolytic activity in vitro. The hydrophilicity of grafted PVC films was investigated by contact angle measurement. Methacrylic acid grafted PVC film showed lower thrombogenicity than that of PVC. It was found that the weight of thrombus formed on grafted PVC was less than that of PVC and glass and decreased with the increase in the graft level. The adhesion of platelets on grafted PVC was retarded after grafting with MAA hydrogels. PMID- 2242397 TI - Soft prosthesis materials based on powdered elastomers. AB - A new class of soft prosthesis material has been developed, based on the combination of a powdered elastomer and a methacrylate monomer that polymerizes to an elastomer. Such systems are processable by conventional dental technology. This principle avoids the use of plasticizers. Natural rubber, butadiene styrene and butadiene acrylonitrile elastomers have been used, together with a number of higher alkyl methacrylates (C8-C13) and 2-ethoxyethyl methacrylate. Such systems have been evaluated with respect to mechanical properties, including tear strength, adhesion to denture base poly(methyl methacrylate), water sorption and visco-elastic properties. A number of potentially viable systems have emerged, which may be useful in external prostheses. Many have high long-term water absorption, which makes questionable their long-term usefulness interorally. Nevertheless, there is still considerable scope for development in this area. PMID- 2242396 TI - Barium sulphate-loaded p(HEMA) microspheres as artificial emboli: preparation and properties. AB - Poly(2-hydroxyethyl methacrylate) p(HEMA) microspheres of good spherical geometry (diameter 90-1500 microns) encapsulated with 40-50% barium sulphate to impart radiopaque properties were prepared by a solvent evaporation process. These microspheres were cross-linked by reacting with hexamethylene diisocyanate (HMDI) or by gamma-irradiation in the presence of ethylene glycol dimethacrylate (EGDM) in n-heptane. Microspheres with a porous structure and a rough surface were also made by the incorporation of NaCl along with BaSO4. The effects of concentration of the polymer solution, concentration of the stabilizing agent, concentration of BaSO4, viscosity of the dispersion medium and ratio of the dispersed phase to the dispersion medium on the formation, stability and particle size distribution of the microspheres were investigated. PMID- 2242398 TI - Fretting corrosion studies of universal femoral head prostheses and cone taper spigots. AB - Short-duration, cyclically loaded, axial, fretting corrosion tests were designed and performed to compare the fretting behaviour of different metal Howmedica universal heads connected to coated and uncoated metal cone taper spigots. Concurrent axial push-on and pull-off taper friction tests were also performed. There was no measurable fretting debris found in any test and SEM studies of the contact surfaces showed no evidence of fretting. It is concluded that no significant, long-term fretting corrosion of the Vitalium Co-Cr-Mo heads on the Vitallium or uncoated Ti-6AI-4V spigots, nor of the Orthinox stainless steel heads on the Orthinox spigots, is likely to occur in vivo. PMID- 2242399 TI - Mechanical behaviour of zirconia and zirconia-toughened alumina in a simulated body environment. AB - The mechanical properties of a zirconia-toughened alumina (ZTA) and three tetragonal zirconia polycrystal ceramics (TZPs), together with a biograde alumina, have been assessed in a simulated body solution (Ringer's solution). The hardness and fracture toughness of these materials were unchanged from the values in air when the tests were carried out in Ringer's solution; there was an instantaneous fall in strength in Ringer's solution but this was considered acceptable. However, ageing for long periods in Ringer's solution promoted a surface layer of monoclinic zirconia. This was accompanied by a strength decrement and it is concluded that these yttria-stabilized ZTA and TZP materials are unsuitable as implant materials. PMID- 2242400 TI - Studies of the solubility of different calcium phosphate ceramic particles in vitro. AB - In vitro solubility tests of hydroxyapatite, tetracalcium phosphate or tricalcium phosphate particles were performed in lactate, citrate, Gomoris or Michaelis buffer with pH 6.2 or 7.2 and in aqua destillata. The results showed that in general the solubility decreased in the order tetracalcium phosphate greater than tricalcium phosphate greater than hydroxyapatite, except for lactate or citrate buffer where the solubility order was tetracalcium phosphate = tricalcium phosphate greater than hydroxyapatite. The influence of the specific buffer used is much larger than either pH or specific calcium phosphate salt tested. The pH stability of lactate buffer and aqua destillata is very low, the other buffer solvents had a rather stable pH value. PMID- 2242401 TI - Behaviour of tricalcium phosphate and hydroxyapatite granules in sheep bone defects. AB - Granules of hydroxyapatite (HA) and tricalcium phosphate (TCP) were implanted in separate holes drilled in mandibular bone of sheep to check the bone growth and in vivo behaviour of the materials. The experiment was performed in three sheep, killed respectively at 4, 8, 12 month. Samples of bone with the materials were explanted, microradiographed and sectioned to evaluate the interface under optical and electron scanning electron microscope. The hole, left empty as a reference, showed no full repair; whereas 4 month after implantation the TCP granules induce total repair of the hole. HA granules crumbled and no new bone induction was seen even 12 month after implantation. PMID- 2242402 TI - Biocompatibility of elastin-fibrin material in the rat. AB - Biocompatibility and biodegradability of a new elastin-fibrin material were investigated in several organs and tissues of the rat. It has been demonstrated that the material was quite well tolerated in all cases, except in bone marrow. Its use is considered in several aspects of reparative or constructive surgery. PMID- 2242404 TI - Fibrous carbon implants for the maintenance of bone volume after tooth avulsion: first clinical results. AB - When the avulsion of the last teeth of a patient is necessary, we propose to maintain the bone mass in order to improve the prosthetic conditions. For this purpose, we use fibrous carbon which is a biocompatible material well tolerated by the surrounding tissues. The results are reported of 10 yr of clinical use of fibrous carbon roots implanted in 38 alveoli of 26 patients with a mean follow-up of 34 month. There were 26 accepted artificial roots and 12 failures. The causes of failure are principally: (1) absent external bone wall near implanted alveoli (presence of the four bone walls is necessary); (2) existing local inflammation near implant site area. PMID- 2242403 TI - Effect of cytochrome P-450 inhibition and stimulation on intensity of polyethylene degradation in microsomal fraction of mouse and rat livers. AB - Polyethylene (PE) is degraded in microsomal fractions of mouse and rat livers with the formation of carbonyl groups. Infrared spectroscopy demonstrated formation of predominantly ketone groups and to a lesser degree ester and aldehyde groups. The inhibition and stimulation of cytochrome P-450 in mouse livers affected the formation of oxidative groups on PE. Phenobarbital doses of 3 x 0.05 mg per mouse increased the concentration of cytochrome P-450 and ketone groups on PE, whereas the vaccine Propionibacterium acnes (0.5 mg) and its pyridine fraction (0.5 and 1 mg) had the opposite effect. The coherence of cytochrome P-450 with oxidative changes on PE is compared and discussed with findings on implants in man. PMID- 2242405 TI - Sampling strategies for distances between DNA sequences. AB - An international effort is now underway to obtain the DNA sequence for the entire human genome (Watson and Jordan, 1989, Genomics 5, 654-656; Barnhart, 1989, Genomics 5, 657-660). This Human Genome Initiative will generate sequence data from several species other than humans, and will result in several copies per species of at least some regions of the genome. Although the project has generated much interest, it is but one aspect of the widespread effort to generate DNA sequence data. Published sequences are collected in common databases, and release 63 of GenBank in March 1990 contained 40,127,752 bases from 33,337 reported sequences (News from GenBank 3; Mountain View, California: Intelligenetics, Inc., 1990). Large though this database is, it is only about 1% of the number of bases in the human genome. Interpretations of data of such magnitude are going to require the collaborative efforts of biometricians and molecular biologists, and an aim of this paper is to show that there is also a role for readers of this journal in the design of surveys of DNA sequences. Discussion here will center on the use of sequence data in evolutionary studies, where some region of DNA is sequenced in several different species. The object is to infer the evolutionary history of that particular region, or of the species themselves. Statistical issues in the very important studies on sequences to locate and characterize regions responsible for human diseases will not be addressed here. We will discuss appropriate ways of measuring distances between DNA sequences and of predicting the sampling properties of the distances. There are procedures for inferring evolutionary histories for a set of elements that depend on a matrix of distances between each pair of elements, and the precision of resulting trees must be influenced by the precision of the distances. We will show that account needs to be taken of two sampling processes--the sampling of sequences by the investigator ("statistical sampling"), and the sampling of genetic material involved in the formation of offspring from a parental population ("genetic sampling"). PMID- 2242406 TI - Logistic regression in capture-recapture models. AB - The effect of population heterogeneity in capture-recapture, or dual registration, models is discussed. An estimator of the unknown population size based on a logistic regression model is introduced. The model allows different capture probabilities across individuals and across capture times. The probabilities are estimated from the observed data using conditional maximum likelihood. The resulting population estimator is shown to be consistent and asymptotically normal. A variance estimator under population heterogeneity is derived. The finite-sample properties of the estimators are studied via simulation. An application to Finnish occupational disease registration data is presented. PMID- 2242407 TI - Approximate interval estimation of the difference in binomial parameters: correction for skewness and extension to multiple tables. AB - Recently, Beal (1987, Biometrics 43, 941-950) found Mee's modification of Anbar's approximate interval estimation for the difference in binomial parameters to be a good choice in small sample sizes. As this method can be derived from the score theory of Bartlett, it is easily corrected for skewness. Exact numerical evaluation shows that this correction is not as important for this case as for the ratio of binomial parameters (Gart and Nam, 1988, Biometrics 44, 323-338). The score theory is also used to extend this method to the stratified or multiple table case. Thus, good approximate interval estimates for differences, ratios, and odds ratios of binomial parameters can all be derived from the same general theory. PMID- 2242408 TI - Some covariance models for longitudinal count data with overdispersion. AB - A family of covariance models for longitudinal counts with predictive covariates is presented. These models account for overdispersion, heteroscedasticity, and dependence among repeated observations. The approach is a quasi-likelihood regression similar to the formulation given by Liang and Zeger (1986, Biometrika 73, 13-22). Generalized estimating equations for both the covariate parameters and the variance-covariance parameters are presented. Large-sample properties of the parameter estimates are derived. The proposed methods are illustrated by an analysis of epileptic seizure count data arising from a study of progabide as an adjuvant therapy for partial seizures. PMID- 2242409 TI - Nonlinear mixed effects models for repeated measures data. AB - We propose a general, nonlinear mixed effects model for repeated measures data and define estimators for its parameters. The proposed estimators are a natural combination of least squares estimators for nonlinear fixed effects models and maximum likelihood (or restricted maximum likelihood) estimators for linear mixed effects models. We implement Newton-Raphson estimation using previously developed computational methods for nonlinear fixed effects models and for linear mixed effects models. Two examples are presented and the connections between this work and recent work on generalized linear mixed effects models are discussed. PMID- 2242410 TI - Testing nonlinear regression parameters under heteroscedastic, normally distributed errors. AB - Likelihood ratio tests for parameters estimated assuming normally distributed errors are examined under a variety of homoscedastic and heteroscedastic variance assumptions. It is assumed that gamma ij, the jth observation from the ith population, is distributed as N[mu(chi ij, beta i), (sigma i mu(chi ij, beta i)theta i)2]. By varying sigma 2i and theta i, this model contains the most obvious examples of homoscedastic and heteroscedastic variability. Under this model, the null hypothesis of equal beta i's can easily be tested using the likelihood ratio criterion. Also considered is the two-sample chi-square statistic, chi 2t = U'S-1 U, where U is the difference vector of nonlinear least squares parameter estimates and S is an estimate of the covariance matrix of U. Monte Carlo simulation using the von Bertalanffy growth curve as an example is used to evaluate several test statistics for Type I error rates under different sampling assumptions. PMID- 2242411 TI - Interpreting plots of a multidimensional dose-response surface in a parallel coordinate system. AB - The dose-response surface for a combination of drugs is a multidimensional figure. Consequently, it is not possible to view such a surface using orthogonal axes when the number of dimensions exceeds 3. Parallel axes have been used to represent hyperdimensional figures. This paper reports on the use of parallel coordinate axes to plot the dose-response surface and its contours of constant response (isobols) for a combination of drugs. It is shown that patterns formed by intersecting line segments in the parallel system can aid in the interpretation of the fitted dose-response surface. More generally, analytic results are developed that permit the ready visualization and characterization of interaction effects of a polynomial model. PMID- 2242412 TI - Efficient design for estimation of median lethal dose and quantal dose-response curves. AB - The results of quantal dose-response experiments are often summarized by an estimate of the "median lethal dose," denoted LD50, and many sequential designs have been proposed for efficient estimation of LD50. These designs strive to produce a sequence of trials at dose levels that get closer and closer to LD50. Consequently, they may not provide very good estimates of the overall shape of the dose-response curve. In this paper we propose guidelines for the design of experiments that estimate LD50 fairly efficiently and that also allow for efficient global estimation of the curve. PMID- 2242413 TI - Implementation of group sequential logrank tests in a maximum duration trial. AB - To control the Type I error probability in a group sequential procedure using the logrank test, it is important to know the information times (fractions) at the times of interim analyses conducted for purposes of data monitoring. For the logrank test, the information time at an interim analysis is the fraction of the total number of events to be accrued in the entire trial. In a maximum information trial design, the trial is concluded when a prespecified total number of events has been accrued. For such a design, therefore, the information time at each interim analysis is known. However, many trials are designed to accrue data over a fixed duration of follow-up on a specified number of patients. This is termed a maximum duration trial design. Under such a design, the total number of events to be accrued is unknown at the time of an interim analysis. For a maximum duration trial design, therefore, these information times need to be estimated. A common practice is to assume that a fixed fraction of information will be accrued between any two consecutive interim analyses, and then employ a Pocock or O'Brien Fleming boundary. In this article, we describe an estimate of the information time based on the fraction of total patient exposure, which tends to be slightly negatively biased (i.e., conservative) if survival is exponentially distributed. We then present a numerical exploration of the robustness of this estimate when nonexponential survival applies. We also show that the Lan-DeMets (1983, Biometrika 70, 659-663) procedure for constructing group sequential boundaries with the desired level of Type I error control can be computed using the estimated information fraction, even though it may be biased. Finally, we discuss the implications of employing a biased estimate of study information for a group sequential procedure. PMID- 2242414 TI - The Cox proportional hazards model with change point: an epidemiologic application. AB - In this paper, we develop the Cox proportional hazards model with special structured time-dependent covariates in the context of prospective epidemiologic studies. Our model possesses the following two features: (i) different relative risk parameters are allowed for early versus late onset of the disease of interest; (ii) an additional parameter is introduced so that specification is not required for the time (age) at which a change of the magnitude of the relative risks takes place, the so-called change point. Some difficulties with statistical inference for the proposed model are briefly discussed, and the large-sample distribution of a test for no change point is derived. As an illustration, we apply the model to a set of data gathered on a group of white male medical students of The Johns Hopkins Medical School enrolled between 1948 and 1964. We examine the hypothesis that the effect of reactivity to the cold pressor test may vary with early versus late onset of hypertension. PMID- 2242415 TI - A partially parametric estimator of survival in the presence of randomly censored data. AB - Many biological or medical experiments have as their goal to estimate the survival function of a specified population of subjects when the time to the specified event may be censored due to loss to follow-up, the occurrence of another event that precludes the occurrence of the event of interest, or the study being terminated before the event of interest occurs. This paper suggests an improvement of the Kaplan-Meier product-limit estimator when the censoring mechanism is random. The proposed estimator treats the uncensored observations nonparametrically and uses a parametric model only for the censored observations. One version of this proposed estimator always has a smaller bias and mean squared error than the product-limit estimator. An example estimating the survival function of patients enrolled in the Ohio State University Bone Marrow Transplant Program is presented. PMID- 2242416 TI - Estimates of absolute cause-specific risk in cohort studies. AB - In this paper we study methods for estimating the absolute risk of an event c1 in a time interval [t1, t2], given that the individual is at risk at t1 and given the presence of competing risks. We discuss some advantages of absolute risk for measuring the prognosis of an individual patient and some difficulties of interpretation for comparing two treatment groups. We also discuss the importance of the concept of absolute risk in evaluating public health measures to prevent disease. Variance calculations permit one to gauge the relative importance of random and systematic errors in estimating absolute risk. Efficiency calculations were also performed to determine how much precision is lost in estimating absolute risk with a nonparametric approach or with a flexible piecewise exponential model rather than a simple exponential model, and other calculations indicate the extent of bias that arises with the simple exponential model when that model is invalid. Such calculations suggest that the more flexible models will be useful in practice. Simulations confirm that asymptotic methods yield reliable variance estimates and confidence interval coverages in samples of practical size. PMID- 2242417 TI - Maximum likelihood estimation for the negative binomial dispersion parameter. PMID- 2242418 TI - Stratton lecture 1989. Thrombosis and inflammation as multicellular processes: pathophysiologic significance of transcellular metabolism. PMID- 2242419 TI - Regulation of human B-cell ontogeny. PMID- 2242420 TI - Silent infections with human immunodeficiency virus type 1 are highly unlikely in multitransfused seronegative hemophiliacs. AB - We used the polymerase chain reaction (PCR) to determine the frequency of silent human immunodeficiency virus type 1 (HIV-1) infections in seronegative high-risk individuals with hemophilia who had been exposed to contaminated blood products more than 3 years previously. In a cross-sectional study of a cohort of 57 prospectively followed seronegative hemophiliacs who received multiple transfusions before 1986, HIV-1 proviral DNA was found transiently in only one patient. These data suggest that the rate of HIV infection among high-risk antibody negative individuals with hemophilia is very low to absent, in the range of 0% to 2%. These findings should provide considerable reassurance to seronegative persons with hemophilia and their sexual partners. PMID- 2242421 TI - Inhibition of interleukin-2-induced tumor necrosis factor release by dexamethasone: prevention of an acquired neutrophil chemotaxis defect and differential suppression of interleukin-2-associated side effects. AB - High concentrations of tumor necrosis factor (TNF) alpha have been detected in the plasma of patients undergoing immunotherapy with interleukin 2 (IL-2), suggesting that this cytokine may play a role in the fever and shocklike state induced by the administration of high-dose IL-2. Dexamethasone has been shown to inhibit the synthesis of TNF by monocytes activated in vitro by endotoxin. To determine if dexamethasone can exert a similar suppressive effect on IL-2-induced TNF synthesis in vivo, the concentration of TNF alpha was measured in plasma samples serially obtained (a) from cancer patients participating in a phase I dose escalation clinical trial with high-dose IL-2 administered in conjunction with dexamethasone (IL-2/Dex) and (b) from patients participating in concurrent studies with IL-2 alone. In contrast to the high plasma levels of TNF alpha detected in patients receiving IL-2 alone, TNF levels in most of the IL-2/Dex patients remained below the threshold of detectability of our TNF radioimmunoassay. The concurrent administration of dexamethasone also prevented the IL-2-induced increase in serum levels of C-reactive protein, a hepatic acute phase reactant whose synthesis is regulated by proinflammatory cytokines such as TNF. The steroid-treated patients also failed to develop the neutrophil chemotactic defect characteristic of IL-2 recipients. The concomitant administration of dexamethasone increased the maximum tolerated dose of IL-2 approximately threefold and markedly reduced the hypotension and organ dysfunction ordinarily observed in these patients. These results demonstrate that dexamethasone inhibits the release of TNF into the circulation of patients undergoing immunotherapy with IL-2. They further suggest that the altered spectrum and reduced severity of IL-2 side effects observed in patients receiving dexamethasone may be attributable in part to the suppressive effect of steroids on IL-2-induced TNF synthesis. PMID- 2242423 TI - Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. AB - A 65 year old patient who was exposed to topical bovine thrombin during cardiac surgery developed markedly prolonged clotting times and a severe bleeding diathesis. Mixing studies with normal plasma failed to correct the clotting times. Platelet transfusions, immunosuppressive and immunomodulatory therapies were ineffective, but plasmapheresis was effective in decreasing clotting times and in the resolution of clinical bleeding events. The patient's purified IgG reacted with bovine thrombin by immunoblotting and enzyme-linked immunosorbent assay (ELISA). However, the IgG reacted minimally with human thrombin. In view of the severe bleeding, a coexisting inhibitor was sought. The patient's factor V activity was 1% of normal and was not corrected by mixing with normal plasma, demonstrating the presence of an inhibitor against factor V. The patient's IgG reacted with both bovine and human factor V. Immunoblotting localized the site of antibody binding to the light chain of activated bovine factor V. Detectable amounts of bovine factor V were found in commercial bovine thrombin preparations by ELISA. The data suggest that patients exposed to topical bovine thrombin may develop antibodies to thrombin and factor V. Anti-thrombin antibodies may mask coexisting factor V inhibitors responsible for clinical bleeding. PMID- 2242422 TI - Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha-granules. AB - We have directly demonstrated that megakaryocytes are a major site of synthesis and storage of transforming growth factor-beta 1 (TGF/beta 1) by combined immunohistochemical, immunocytochemical, and in situ hybridization methods. The presence of TGF/beta 1 messenger RNA (mRNA) in mature megakaryocytes in adult rat spleen and bone marrow (BM) was established by in situ hybridization. Localization of TGF/beta 1 protein to intact alpha-granules of megakaryocytes, its putative storage site, was accomplished in glycol-methacrylate embedded porcine BM with an immunoperoxidase technique and light microscopy. The TGF/beta 1 was sequestered in intracytoplasmic granules in a pattern virtually identical to that of another alpha-granule marker protein, fibrinogen. This observation strongly suggests packaging of TGF/beta 1 into this organelle within megakaryocytes. That TGF/beta 1 mRNA was localized to megakaryocytes suggests that the TGF/beta 1 found in the alpha-granules in platelets originates with megakaryocyte synthesis. The alpha-granule localization of TGF/beta 1, as well as fibrinogen, was also demonstrated in isolated platelets at the ultrastructural level by electronmicroscopy (EM) and postembedding colloidal-gold immunocytochemistry, thus directly demonstrating that alpha-granules are the final storage site for TGF/beta 1 in mature platelets. PMID- 2242424 TI - Analysis of platelet aggregation disorders based on flow cytometric analysis of membrane glycoprotein IIb-IIIa with conformation-specific monoclonal antibodies. AB - Normal primary platelet aggregation requires agonist-mediated activation of membrane GPIIb-IIIa, binding of fibrinogen to GPIIb-IIIa, and cellular events after ligand binding. PAC1 monoclonal antibody distinguishes between resting and activated states of GPIIb-IIIa, and other antibodies preferentially recognize GPIIb (PMI-1) or IIIa (anti-LIBS1) after the binding of fibrinogen or fibrinogen mimetic peptides, such as GRGDSP. Using these antibodies and platelet flow cytometry, we studied two distinct persistent platelet aggregation abnormalities. Platelets from a thrombasthenic variant, which contained near-normal amounts of GPIIb-IIIa, failed to aggregate or bind PAC1 in response to agonists. In addition, GRGDSP, which binds to normal GPIIb-IIIa without prior cell activation, failed to increase the binding of PMI-1 or anti-LIBS1 to the thrombasthenic platelets, suggesting a primary defect in ligand binding. Chromatography of detergent-solubilized platelets on a KYGRGDS affinity column confirmed that the patient's GPIIb-IIIa lacked the fibrinogen binding site. In another patient with myelofibrosis and defective aggregation, PAC1 failed to bind to adenosine diphosphate-stimulated platelets, but did bind when protein kinase C was directly activated with phorbol myristate acetate. Furthermore, the binding of PMI-1 and anti-LIBS1 increased in response to GRGDSP, confirming a defect in agonist mediated fibrinogen receptor activation rather than in fibrinogen binding or events distal to binding. These studies indicate that this immunochemical approach is useful in classification of clinical abnormalities of platelet aggregation as defects in either (a) fibrinogen receptor activation, (b) fibrinogen binding, or (c) postoccupancy events. PMID- 2242425 TI - Induction of in vitro graft-versus-leukemia activity following bone marrow transplantation for chronic myeloid leukemia. AB - We studied the in vitro effects of lymphokine-activated killer (LAK) cells from the peripheral blood of chronic myeloid leukemia (CML) patients after allogeneic and syngeneic bone marrow transplantation (BMT). LAK cells were generated by incubating peripheral blood mononuclear cells from patients post-BMT with recombinant interleukin-2 (IL-2) (500 U/mL) in 10% AB serum for 7 days. They were phenotyped and tested for activity in a standard 4-hour 51Cr release assay (n = 37) and in a CFU-GM assay (n = 24). We found that the LAK cells were mainly activated natural killer cells, but some were CD3+ T cells. In the 51Cr release assay LAK cells from 20 of 33 (61%) allogeneic and 2 of 4 syngeneic recipients killed recipient CML cells and in 22 of 37 (60%) cases also killed the HLA disparate CML cells. In the CFU-GM assay the LAK cells incubated together with the CML cells in liquid culture before plating inhibited (P less than .05) colony growth in 16 of 22 allogeneic and 2 of 2 syngeneic recipients. Cell-cell contact was necessary for optimal effect. There was little or no inhibition of proliferation of donor marrow CFU-GM. This in vitro graft-versus-leukemia (GVL) effect could also be demonstrated after LAK effectors were depleted of CD3+ T cells. It was inducible in recipients of both T cell-depleted and T cell-replete donor marrow and in recipients with or without graft-versus-host disease. These results suggest that a major histocompatibility complex-unrestricted GVL effect is inducible following allogeneic and syngeneic BMT. The use of IL-2/LAK cells after BMT could reduce the risk of relapse. PMID- 2242426 TI - The effect of desferrithiocin, an oral iron chelator, on T-cell function. AB - Desferrithiocin is a new, potent, orally available iron chelator. To determine whether this drug might be useful not only for iron-overload but also for immunosuppression, we studied the in vitro effects of desferrithiocin on T lymphocyte function. Like deferoxamine, desferrithiocin inhibited, in a dose dependent fashion, mitogen- and lectin-induced proliferation of both human and murine T cells. It was active at a concentration of 10 micrograms/mL. The inhibition of proliferation was reversed by ferrous chloride, but not by other metal salts, recombinant IL-2, or conditioned medium. Desferrithiocin also inhibited proliferation of constitutively dividing, and factor-independent EBV transformed B cell and leukemic T-cell lines. Although desferrithiocin inhibited the induction of cytotoxic T lymphocyte (CTL) activity, it did not inhibit CTL- or natural killer-induced cytotoxicity. The agent did not inhibit the expression of activation antigens such as the IL-2 receptor on T cells, nor early measures of T-cell activation such as the influx of intracellular calcium. Thus, desferrithiocin, like deferoxamine, is a potent and reversible inhibitor of T cell proliferation. This anti-proliferative effect inhibits T-cell function. Bioavailability after oral administration is a unique property of desferrithiocin, and would make it an attractive alternative to deferoxamine. Its immunomodulating properties may therefore be exploited in vivo to inhibit graft rejection or autoreactive T cells. PMID- 2242427 TI - Deletion of the human retinoblastoma gene in primary leukemias. AB - As an initial step in evaluating the role of tumor suppressor genes in leukemogenesis, we surveyed primary leukemia cells from 130 patients for possible deletion of the retinoblastoma susceptibility (Rb) gene by Southern blot analysis. Two of them clearly showed homozygous deletion of Rb alleles. The first patient was a pre-B acute lymphoid leukemia (ALL) associated with a cytogenetic translocation: t(14;16)(q24;q22). The deletion was located at the 3' portion of the Rb gene, very close to the site of Rb gene deletion recently identified in an ALL cell line. The absence of Rb110 protein was further confirmed by Western blot analysis. The second patient was a chronic myelomonocytic leukemia (CMMoL), terminated in acute blastic transformation. Deletion of the 5' portion of Rb gene was found in leukemic cells in the chronic stage. The results indicated that inactivation of the Rb gene occurred in certain cases of leukemia. Its significance warrants further study. PMID- 2242428 TI - Association of bcl-1 rearrangements with lymphocytic lymphoma of intermediate differentiation. AB - Previous studies using classical cytogenetics have demonstrated the presence of the t(11;14) (q13;q32) chromosomal translocation in some cases of lymphocytic lymphoma of intermediate differentiation (IDL), a distinct type of low grade B cell lymphoma. This finding suggested that the bcl-1 region (located at band q13 of chromosome 11) might be involved in this neoplasm. Using a genomic probe from the major breakpoint area of the bcl-1 locus, we identified rearrangements of the bcl-1 region in 10 of 19 cases, 2 of which comigrated with a rearranged allele of the immunoglobulin heavy chain gene joining region. In contrast, bcl-1 rearrangements were not found in other types of low grade B-cell lymphoma, specifically in 36 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 27 cases of follicular lymphoma (FL). To further assess the molecular pathology of IDL, we analyzed these cases for rearrangements of the bcl-2 proto-oncogene, which is associated primarily with follicular lymphomas. None of the 19 cases of IDL had rearrangements. Furthermore, none of the 36 cases of CLL/SLL showed bcl-2 rearrangements, whereas, as expected, 21 of 27 cases of FL had rearrangements of the bcl-2 locus. Our findings demonstrate an association between a rearranged bcl-1 region with approximately 50% of IDLs and suggest that abnormalities of this locus may be important in the pathogenesis of IDL. PMID- 2242429 TI - Response patterns of hairy cell leukemia to B-cell mitogens and growth factors. AB - The effect of mitogens and/or recombinant B-cell growth factors (M/GFs) on the in vitro growth of hairy cells was examined. Tumor cells were isolated from the spleens of four patients with hairy cell leukemia (HCL) by Ficoll-Hypaque sedimentation and E-rosetting. Enrichment for tumor cells was confirmed with intracytoplasmic immunoglobulin (Ig) staining, tartrate resistant acid phosphatase (TRAP) staining, and staining using monoclonal antibodies (MoAbs) directed at B, T, myeloid, and monocytoid antigens (Ags) in indirect immunofluorescence assays. Tumor cells were B1(CD20)+ B2(CD21)- B4(CD19)+ IL 2R(CD25)+ PCA-1 +/- TRAP+. HCLs neither synthesized DNA nor secreted Ig in response to culture with granulocyte-macrophage colony-stimulating factor (GM CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, or IL 6. However, a proliferative response (stimulation index greater than or equal to 3.0) without Ig secretion was triggered in HCLs by mitogens or combinations of GFs. Specifically, DNA synthesis was induced at 3 days in three of four HCL samples cultured with Staphylococcus aureus Cowan A (SAC) or the combination of phorbol ester (TPA) and the calcium ionophore A 23187 (Ca2+); DNA synthesis was triggered later (day 7) by tumor necrosis factor (TNF) or by IL-4 and IL-5. In contrast, the fourth patient, a nonresponder to SAC or TPA/Ca2+, demonstrated increased DNA synthesis at day 3 when cocultured with IL-4 and IL-5. Both autoradiography and staining with antibromodeoxyuridine (BrdU) MoAb conjugated to fluorescein confirmed DNA synthesis by only a minority (5% to 23%) of tumor cells within each patient. Dual staining confirmed that responsive cells were both BrdU+ and TRAP+. DNA synthesis induced by TPA/Ca2+ was blocked specifically by anti-IL-6 Ab; in contrast, the HCL proliferative response to SAC, TNF, or IL-4 and IL-5 was not inhibited by anti-IL-6 Ab. alpha-Interferon inhibited the response to TPA/Ca2+, TNF, or IL-4 and IL-5 without any effect on response to SAC. Finally, peroxidase-antiperoxidase staining demonstrated that HCLs are induced by TPA/Ca2+, but not by SAC, to produce intracytoplasmic IL-6. These data demonstrate IL-4, IL-5, and IL-6 mediated DNA synthesis by HCLs in vitro and suggest a possible in vivo role for these growth factors in the pathophysiology of HCL. PMID- 2242430 TI - The amino-terminal 29- and 72-Kd fragments of fibronectin mediate selective monocyte recruitment. AB - Proteolytic fragments of fibronectin (Fn) can possess properties not inherent to intact Fn. Previously, only mixtures of low molecular weight Fn fragments, and the 120-Kd fibroblastic cell-binding segment, but not intact Fn, were shown to be selectively chemotactic for human monocytes (MOs). In order to determine if other structural domains of Fn were responsible, we tested six Fn fragments. The amino terminal 72-Kd fragment at 1.5 microns was about 75% as potent as zymosan activated serum (ZAS). Its amino-terminal 29-Kd degradation product at 1.0 micron was about one third as potent as ZAS. Checkerboard analysis confirmed chemotaxis. Complexing gelatin to 72-Kd fragments reduced MO chemotaxis by 28% to 30%. Reducing disulfide bonds in 29- and 72-Kd segments had no effect. A synthetic peptide containing the thrombin cleavage site between the 29- and 50-Kd segments of the 72-Kd fragment was chemotactic. The 50-, 190/170-, 35-, and 160/150/120-Kd fragments, and intact Fn were not chemotactic for MOs. The data suggest that the 72-Kd fragment and its 29-Kd subfragment are additional Fn fragments that mediate selective MO chemotaxis. We speculate that proteinases present at inflammatory sites can liberate such fragments that selectively recruit MOs. PMID- 2242431 TI - Effect of hemoglobin oxidation products on the stability of red cell membrane skeletons and the associations of skeletal proteins: correlation with a release of hemin. AB - Oxidative injury to hemoglobin (Hb) leads to formation of methemoglobin (MetHb), reversible hemichromes (rHCRs), and irreversible hemichromes (iHCRs). iHCRs precipitate and form Heinz bodies that attach to the red cell membrane causing injury that leads to hemolysis. The molecular mechanisms of this membrane damage have not been fully elucidated. We have studied the effect of Hb oxidation products on the mechanical stability of red cell membrane skeletons and the associations of membrane skeletal proteins. Hb and MetHb stabilized the isolated membrane skeletons, whereas further oxidation to rHCRs abolished this stabilizing effect. Crude iHCRs prepared by phenylhydrazine oxidation of Hb destabilized membrane skeletons by decreasing formation of the spectrin-protein 4.1-actin complex, the effect similar to that of pure hemin. Whereas virtually no hemin was released from Hb and MetHb, high concentrations of hemin were released from crude iHCR preparations. After removal of this hemin fraction by Dowex resin, the iHCRs lost their destabilizing effect. We conclude that as the oxidation of Hb proceeds, the stabilizing effect of Hb on the membrane skeleton is gradually lost and the deleterious effect increases. The destabilization of the red cell membrane skeleton in the presence of crude iHCR is caused by release of hemin, which lowers the stability of membrane skeleton by weakening the spectrin-protein 4.1-actin interaction. PMID- 2242432 TI - Molecular and hematologic characterization of Scottish-Irish type (epsilon gamma delta beta)zero thalassemia. AB - The DNA deletion associated with an example of (epsilon gamma delta beta)zero thalassemia (Scottish-Irish type) was characterized. The deletion is approximately 205 kb in length and involves the epsilon, G gamma, A gamma, delta, and beta globin genes. The breakpoint is located 263 bp 3' to exon 3 of the beta globin gene. An LI (KpnI) repeat element approximately 320 bp in size is found at the 3' end of the novel DNA sequence. Different clinical phenotypes for three heterozygous neonates suggest that the deletion alone does not predict severity of (epsilon gamma delta beta)zero thalassemia at this age. PMID- 2242433 TI - Sickle erythrocytes inhibit human endothelial cell DNA synthesis. AB - Patients with sickle cell anemia experience severe vascular occlusive phenomena including acute pain crisis and cerebral infarction. Obstruction occurs at both the microvascular and the arterial level, and the clinical presentation of vascular events is heterogeneous, suggesting a complex etiology. Interaction between sickle erythrocytes and the endothelium may contribute to vascular occlusion due to alteration of endothelial function. To investigate this hypothesis, human vascular endothelial cells were overlaid with sickle or normal erythrocytes and stimulated to synthesize DNA. The erythrocytes were sedimented onto replicate monolayers by centrifugation for 10 minutes at 17 g to insure contact with the endothelial cells. Incorporation of 3H-thymidine into endothelial cell DNA was markedly inhibited during contact with sickle erythrocytes. This inhibitory effect was enhanced more than twofold when autologous sickle plasma was present during endothelial cell labeling. Normal erythrocytes, with or without autologous plasma, had a modest effect on endothelial cell DNA synthesis. When sickle erythrocytes in autologous sickle plasma were applied to endothelial monolayers for 1 minute, 10 minutes, or 1 hour and then removed, subsequent DNA synthesis by the endothelial cells was inhibited by 30% to 40%. Although adherence of sickle erythrocytes to the endothelial monolayers was observed under these experimental conditions, the effect of sickle erythrocytes on endothelial DNA synthesis occurred in the absence of significant adherence. Hence, human endothelial cell DNA synthesis is partially inhibited by contact with sickle erythrocytes. The inhibitory effect of sickle erythrocytes occurs during a brief (1 minute) contact with the endothelial monolayers, and persists for at least 6 hours of 3H-thymidine labeling. These results indicate that interaction between sickle erythrocytes and the endothelium may result in altered endothelial function. This altered endothelial function may contribute to the development of vascular occlusive phenomena in patients with sickle cell anemia. PMID- 2242434 TI - Evaluation of leukocyte removal filters modelled by use of HIV-infected cells and DNA amplification. AB - The concept of reducing cell-associated blood-borne viruses (BBVs) by filtration of the vector leukocytes from blood collected for transfusion has led to the development of high efficiency filters. Improved filtration technology demands newer methodology to accurately estimate the residual cells. We have developed an experimental model based on the hemocytometer counts and the polymerase chain reaction (PCR), performed on the lymphocytes derived from the units of red cell mass inoculated with marker cells (H9) persistently carrying cell-associated human immunodeficiency virus DNA (CA-HIV). We measured the efficiency of 6 units of a prototype filter using our model and found an estimated mean of less than 4 residual cells per milliliter in the filtered blood. This represents a mean 5.84 log10 reduction of normal PBMC and CA-HIV in pre- and post-filtration aliquots and exemplifies the application of our model for evaluating a new generation of blood filters. Our model illustrates that a biological tracer (ie, DNA) is a better measure of the efficacy of a leukocyte filter than the hemocytometric enumeration of pre- and post-filtration PBMC concentrates. PMID- 2242435 TI - Desferrioxamine provocative test: methodology for estimating iron and total iron binding capacity. PMID- 2242436 TI - Identity of Wegener's autoantigen (p29) with proteinase 3 and myeloblastin. PMID- 2242437 TI - Peripheral T-cell lymphoma associated with hemophagocytic syndrome and hemophagocytic lymphohistiocytosis of children: do they share something? PMID- 2242438 TI - A beta-thalassemia carrier with normal sequence within the beta-globin gene. PMID- 2242439 TI - Role of vasopressin in cardiovascular and blood pressure regulation. AB - At low concentrations and in physiologic states vasopressin is a potent antidiuretic hormone. Its cardiovascular effects have been more complex and their role in circulatory adjustments to hypovolemia and hypotension difficult to define with precision. Although recognized as a powerful vasoconstrictor, its pressor effect in intact animals, even at high concentrations, is minimal. The reasons for this blunted pressor response have been explored. This report is a review of previously published work from our laboratories which highlights the direct and indirect vasodilator actions of this hormone in animals and humans. The indirect vasodilator effect is caused by inhibition of sympathetic efferents, and facilitation of the baroreflex through a central action of the hormone and its sensitization of arterial baroreceptors as well as cardiac afferents. PMID- 2242440 TI - Mechanisms involved in serotonin-induced vasodilatation. AB - In vitro investigations have identified three major mechanisms which could contribute to the vasodilator action of serotonin (5-hydroxytryptamine, 5-HT): direct vascular smooth muscle relaxation; prejunctional inhibition of noradrenaline release from vascular sympathetic nerve terminals; and release of endothelium-derived relaxing factor (EDRF). In vivo studies have shown that in pig and cat common carotid circulations, rabbit hindquarter and mesenteric circulations, and rat systemic vasculature, direct vascular smooth muscle relaxation may be the predominant mechanism involved, but the contribution of EDRF release remains to be established. In other circulations in vivo (dog femoral and common carotid), prejunctional inhibition of vascular sympathetic tone is the predominant mechanism responsible for serotonin-induced vasodilatation. All of these actions are mediated by 5-HT1-like receptors, but different subtypes seem to be involved in each of these mechanisms. The prejunctional inhibitory receptor has been the most studied; depending on the tissue, these subtypes may resemble 5-HT1A, 5-HT1B, 5-HT1C or 5-HT1D binding sites, or the contractile receptor in dog saphenous vein. PMID- 2242441 TI - Decreased activity of the sodium-calcium exchanger in tail artery of stroke-prone spontaneously hypertensive rats. AB - The ability of the Na-Ca exchanger to modify vascular relaxation was studied in rings isolated from tail arteries of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). The arteries were contracted with norepinephrine (NE) 1 microM and after stabilization they were transferred to a Ca-free physiological salt solution still in presence of NE. The time to 50% relaxation (T-50) in these conditions was significantly greater in SHRSP (78 +/- 7 s) than in WKY (50 +/- 7 s). When the calcium pump was stopped with vanadate (VAN), the Ca uptake by the sarcoplasmic reticulum with ryanodine (RY) and the Na Ca exchanger with a Na-free PSS, the relaxation was slowed (T-50 increased to 198 +/- 16 s in SHRSP and to 162 +/- 14 s in WKY). Releasing the Na-Ca exchanger only (i.e. still with VAN and RY but with normal Na in the bath) the T-50 for relaxation in Ca-free PSS was, in WKY, nearly as fast as in control conditions (54 +/- 8 s). However, the Na-Ca exchanger in SHRSP was not so effective, and the T-50 for relaxation was slower than in control conditions (122 +/- 10 s). We conclude that the activity of the Na-Ca exchanger is depressed in tail arteries of SHRSP. This abnormality in resistance vessels, would contribute to the enhanced vascular tone present in hypertension. PMID- 2242442 TI - Resistance artery tone is influenced independently by pressure and by flow. AB - The responses of rabbit resistance arteries to pressure and flow have been examined using two in vitro techniques--when mounted isometrically in a myograph and when perfused using a video system that automatically registers diameter. The latter approach allows pressure and flow to be independently controlled. Under such circumstances three responses were studied; myogenic contraction and flow dependent constriction and dilation. All responses occurred after endothelium removal and were unaffected by indomethacin (10(-60 M). The pressure and flow effects can be elicited separately and have different ionic bases. The effective stimulus for the myogenic response is stretch and that for flow is presumably shear stress. The mechano-transducers for these effects are different and are located either in the vascular smooth muscle cells or their surrounding extracellular matrix. PMID- 2242443 TI - EDRF in intact vascular networks. AB - X-ray microangiography was used to investigate the role of basal EDRF activity in the isolated rabbit ear, changes in perfusion pressure at different flow rates being correlated with simultaneous changes in diameter in resistance arteries 70 1,000 microns in size. Under conditions of controlled-pressure but not controlled flow perfusion the preparations were shown to autoregulate flow, but only when EDRF activity was inhibited by haemoglobin or L-NMMA. The diameter data indicated that this phenomenon was mediated by a flow- and/or pressure-dependent constrictor response that is normally suppressed by EDRF activity. We also investigated the influence of basal EDRF activity on the geometrical 'optimality' of resistance artery branching, using four models which minimise respectively the total surface area, volume, shear stress (drag) or power losses at bifurcations. EDRF activity was found to maintain optimality in terms of minimum volume and power losses over a wide range of flow rates in pharmacologically constricted preparations. This may allow rapid changes in flow to occur with only small changes in central arterial pressure and also help to minimise cardiac work. PMID- 2242444 TI - Endothelium-derived hyperpolarizing factor. AB - Although nitric oxide appears to be the major endothelium-derived relaxing factor (EDRF), it cannot explain all endothelium-dependent responses of isolated arteries. Thus, acetylcholine causes an endothelium-dependent, transient hyperpolarization, which is due to the release from the endothelial cells of a diffusible substance (endothelium-derived hyperpolarizing factor, EDHF) other than nitric oxide. The muscarinic receptors on the endothelium that trigger the release of EDHF belong to the M1-muscarinic subtype, while those activating the liberation of EDRF are M2-muscarinic in nature. The importance of endothelium dependent hyperpolarization varies among different blood vessels. The hyperpolarization, and the resulting relaxation caused by EDHF can be attributed to an increase in K+ conductance in the vascular smooth muscle. Although the nature of EDHF remains elusive, it may be a labile metabolic of arachidonic acid. PMID- 2242445 TI - Mechanoreception by the endothelium: mediators and mechanisms of pressure- and flow-induced vascular responses. AB - Mechanoreception, a widely distributed sensory modality, has been shown to be present in certain blood vessels. Changes in physical forces, like sudden increase of transmural pressure or flow velocity (shear stress), trigger changes in blood vessel diameter; the former reduces it while the latter increases vessel caliber. These changes in diameter, which are the result of contraction and relaxation of vascular smooth muscle in the blood vessel media, can serve the purpose of physiological regulation of blood flow (autoregulation) and protection of the intima against damages from high shear forces. The precise location of mechanosensor(s) and the mechanism of mechanoreception and signal transduction are poorly understood. Accumulating evidence suggests that the endothelium may be a site of mechanoreception and that changes in the synthesis/release of endothelium-derived relaxing (EDRF, EDHF, PGI2) and contracting factors (EDCF) result in altered vascular smooth muscle tone and vessel caliber. Increased shear stress stimulates the release of EDRF and PGI2 probably via activation of a K+ channel (inward rectifier) in endothelial cell membrane. Endothelium-dependent vascular contraction evoked by increased transmural pressure may be the result of (1) reduced release of EDRF (canine carotid artery) and (2) stimulation of the release of a still unidentified EDCF(s) (feline cerebral artery). Thus the endothelium can serve as pressure and flow sensor and is capable of transducing changes in mechanical forces into changes of vascular smooth muscle tone by modulating the release of endothelium-derived vasoactive factors. The physiological importance of the mechanoreception by endothelial cells in the intact circulation remains to be determined. PMID- 2242446 TI - Impaired dilatation of cerebral arterioles in chronic hypertension. AB - Several mechanisms impair cerebral vasodilatation during chronic hypertension. First, the external diameter of cerebral arterioles is reduced during chronic hypertension by structural 'remodeling'. Thus, both vascular hypertrophy and remodeling result in encroachment on the lumen. Second, endothelium-dependent dilatation of cerebral vessels is impaired during chronic hypertension. Third, blood flow through cerebral collaterals is impaired by chronic hypertension, so that an important compensatory mechanism is compromised. Impaired vasodilator responses, together with limitation of increases in collateral blood flow, may predispose to cerebral ischemia and stroke during chronic hypertension. PMID- 2242447 TI - Endothelium-dependent relaxations and chronic vasospasm after subarachnoid hemorrhage. AB - Endothelium-dependent relaxations are abolished in the canine basilar artery after subarachnoid hemorrhage. However, the release of endothelium-derived relaxing factor (EDRF) toward the lumen is not reduced. These findings suggest that the responsiveness of the smooth muscle to EDRF is impaired during chronic vasospasm after subarachnoid hemorrhage. PMID- 2242448 TI - Molsidomine. AB - Molsidomine is an established drug for the treatment of coronary heart disease. It acts via the metabolite SIN-1 through liberation of NO. Experiments have proven the identity of NO and EDRF. Investigation of the molecular mechanism of action of molsidomine/SIN-1 indicate that molecular oxygen initiates NO formation through a one-electron abstraction from the intermediate. Ex vivo experiments in rats and in vitro studies in human coronary arteries showed that marked tolerance is induced with glyceryl trinitrate, whereas prolonged exposure to SIN-1 does not cause tolerance. Responsiveness to SIN-1 is not modified in nitrate-tolerant human arteries. Stimulation of soluble guanylate cyclase underlies the antiaggregatory actions of EDRF. Likewise SIN-1 inhibits platelet aggregation in various models. In dogs and pigs with critical stenosis molsidomine reduced significantly the frequency and the severity of cyclical reductions of coronary blood flow. PMID- 2242449 TI - Mechanism of the vasodilator action of pinacidil. AB - The mechanism of the vasodilator action of pinacidil has been studied in rat mesenteric small arteries. The results show, first, that the use of flux studies to make measurements of ion permeability requires knowledge of the membrane potential, especially as regards K+ permeability. Second, the results confirm that the vasodilator effect of pinacidil is due to an increase in K+ permeability. Lastly, the results suggest that the K+ channels involved are sensitive to glibenclamide. PMID- 2242450 TI - Peptidergic vasodilator nerves in the peripheral circulation and in the vascular beds of the heart and brain. AB - This overview focusses on the ubiquitous presence of immunohistochemically visible peptidergic nerves with vasodilatory function. The nerve fibres are primarily related to the parasympathetic system (vasoactive intestinal polypeptide or VIP), the sympathetic system including the adrenal medulla (enkephalins) and to the sensory system (substance P as well as calcitonin gene related peptide, CGRP). Substance P and probably also CGRP seem to be the mediators of antidromic vasodilatation. Enkephalins appear to be released both from nerve endings and from the adrenomedullary cells. The vasodilatory nerve fibres in the heart distribute both to the coronary vessels and to functionally important parts of the myocardium, where interesting relations exist between the peptidergic flow regulation and contractile force. In the brain the sensory and parasympathetic pathways for VIP and substance P/CGRP have recently been mapped in detail, and a new peptidergic intracranial ganglion has been discovered. The selective electrical stimulation of the sensory and postganglionic parasympathetic fibres, respectively, in the brain circulation has been found to evoke a pronounced flow increase which does not appear to involve cholinergic mediation. There is also experimental evidence that the mentioned systems of fibres may interact with each other and with the sympathetic nervous system by way of neuronal cross-talk. PMID- 2242451 TI - Cholinergic vasodilatation of coronary resistance vessels in dogs, baboons and goats. AB - Intracoronary infusion of acetylcholine produces a prompt increase in coronary blood flow in dogs, but a paradoxical decrease has been reported in baboons and cattle. The action of acetylcholine was reexamined in anesthetized dogs, baboons and goats, with the coronary circulation pump perfused at constant pressure and the heart rate held constant with electrical pacing. Intracoronary infusions of low doses of acetylcholine produced coronary vasodilatation and an increase in coronary venous oxygen tension without a change in cardiac contractility (dP/dt) or myocardial oxygen consumption in all three species. High doses of acetylcholine produced coronary vasodilatation only in dogs, but resulted in a decrease in cardiac contractility and myocardial oxygen consumption accompanied by a decrease in coronary flow in baboons and goats. It is concluded that low doses of acetylcholine produce coronary vasodilatation in all three species, and that the decrease in coronary blood flow observed in baboons and goats at high doses is probably due to local metabolic vasoconstriction secondary to the negative inotropic effects of acetylcholine. PMID- 2242452 TI - Safety and health in the construction industry. PMID- 2242453 TI - Diabetic autonomic neuropathy. PMID- 2242454 TI - Endothelins. PMID- 2242456 TI - Atenolol in essential hypertension during pregnancy. AB - OBJECTIVE: To determine the effect of atenolol on the outcome of pregnancy in women with essential hypertension. DESIGN: Prospective, randomised, double blind, placebo controlled study. SETTING: Hospital clinic. PATIENTS: 33 Women with mild essential hypertension (systolic blood pressure 140-170 mm Hg or diastolic pressure 90-110 mm Hg on two occasions at least 24 hours apart) consecutively referred to two obstetric medical clinics. Four patients in the placebo group were withdrawn from the study: control of blood pressure was inadequate in two, one developed breathlessness, and one changed her mind about participating. The mean gestation in the 29 remaining women on entry to the study was 15.9 weeks. MAIN OUTCOME MEASURES: Blood pressure and birth weight. INTERVENTION: 14 Women received placebo. 15 Women received atenolol 50 mg daily initially, increasing until either the blood pressure was less than 140/90 mm Hg or a dose of 200 micrograms daily was reached. RESULTS: The mean blood pressure on entry was 148/86 mm Hg in the group given atenolol and 144/86 mm Hg in the group given placebo. During treatment the mean diastolic pressure was significantly reduced by atenolol compared with placebo (to 74 v 81 mm Hg; difference in means (95% confidence interval) 7.0 (2.9 to 10.0) mm Hg) but the effect on systolic pressure was marginal (132 v 136 mm Hg; 4.0 (-1.4 to 8.6) mm Hg). Babies in the atenolol group had a significantly lower birth weight than those in the placebo group (2620 g v 3530 g; 910 (440 to 1380)g). CONCLUSION: Atenolol given from the end of the first trimester in patients with mild hypertension is associated with intrauterine growth retardation. When taken in conjunction with the results of a previous study in which methyldopa was given these findings indicate that benefit is unlikely to result from treating mild essential hypertension in pregnancy. PMID- 2242455 TI - Psychological outcomes of different treatment policies in women with early breast cancer outside a clinical trial. AB - OBJECTIVES: To assess outside a clinical trial the psychological outcome of different treatment policies in women with early breast cancer who underwent either mastectomy or breast conservation surgery depending on the surgeon's opinion or the patient's choice. To determine whether the extent of psychiatric morbidity reported in women who underwent breast conservation surgery was associated with their participation in a randomised clinical trial. DESIGN: Prospective, multicentre study capitalising on individual and motivational differences among patients and the different management policies among surgeons for treating patients with early breast cancer. SETTING: 12 District general hospitals, three London teaching hospitals, and four private hospitals. PATIENTS: 269 Women under 75 with a probable diagnosis of stage I or II breast cancer who were referred to 22 different surgeons. INTERVENTIONS: Surgery and radiotherapy or adjuvant chemotherapy, or both, depending on the individual surgeon's stated preferences for managing early breast cancer. MAIN OUTCOME MEASURES: Anxiety and depression as assessed by standard methods two weeks, three months, and 12 months after surgery. RESULTS: Of the 269 women, 31 were treated by surgeons who favoured mastectomy, 120 by surgeons who favoured breast conservation, and 118 by surgeons who offered a choice of treatment. Sixty two of the women treated by surgeons who offered a choice were eligible to choose their surgery, and 43 of these chose breast conserving surgery. The incidences of anxiety, depression, and sexual dysfunction were high in all treatment groups. There were no significant differences in the incidences of anxiety and depression between women who underwent mastectomy and those who underwent lumpectomy. A significant effect of surgeon type on the incidence of depression was observed, with patients treated by surgeons who offered a choice showing less depression than those treated by other surgeons (p = 0.06). There was no significant difference in psychiatric morbidity between women treated by surgeons who offered a choice who were eligible to choose their treatment and those in the same group who were not able to choose. Most of the women (159/244) gave fear of cancer as their primary fear rather than fear of losing a breast. The overall incidences of psychiatric morbidity in women who underwent mastectomy and those who underwent lumpectomy were similar to those found in the Cancer Research Campaign breast conservation study. At 12 months 28% of women who underwent mastectomy in the present study were anxious compared with 26% in the earlier study, and 27% of women in the present study who underwent lumpectomy were anxious compared with 31% in the earlier study. In both the present and earlier study 21% of women who underwent mastectomy were depressed, and 19% of women who underwent lumpectomy in the present study were depressed compared with 27% in the earlier study.) CONCLUSIONS: There is still no evidence that women with early breast cancer who undergo breast conservation surgery have less psychiatric morbidity after treatment than those who undergo mastectomy. Women who surrender autonomy for decision making by agreeing to participate in randomised clinical trials do not experience any different psychological, sexual, or social problems from those women who are treated for breast cancer outside a clinical trial. PMID- 2242457 TI - Prevalence of symptoms of Raynaud's phenomenon in general practice. AB - OBJECTIVE: To investigate the prevalence of Raynaud's phenomenon in the populations of five general practices. DESIGN: Two populations studied. A questionnaire was given to all new patients attending five general practices over four weeks, and the same questionnaire was sent by post to a random sample of adults from two of the practices. SETTING: General practices in inner London, Merseyside, and Cheshire. SUBJECTS: 1532 Patients who completed questionnaires (1119 who attended the surgeries (response rate unknown) and 413 respondents to the postal survey (response rate 69%)). MAIN OUTCOME MEASURES: Response to questionnaire on symptoms of Raynaud's phenomenon: patients were regarded as having the disease if they had episodes of blanching of the fingers that were precipitated by cold and accompanied by sensory symptoms (pins and needles or numbness). Subsequent interview and clinical appraisal of patients with the disease according to their responses to the questionnaire. RESULTS: The prevalence of Raynaud's phenomenon was 11% (26/231) and 19% (34/182) respectively in men and women who completed the postal questionnaire and 16% (56/357) and 21% (157/762) respectively in those who completed the questionnaire when attending their general practice. Thus the overall rates were slightly higher in women, but there was no effect of age even after adjustment of the rates for practice and method of survey. CONCLUSION: The prevalence of Raynaud's phenomenon is high compared with the low number of patients who seek treatment for the disease. PMID- 2242458 TI - Immunisation in a curative setting. AB - OBJECTIVE: To study the uptake of vaccination offered to women and children attending a curative health facility. DESIGN: Prospective survey over eight months of the uptake of vaccination offered to unimmunised women and children attending a diarrhoeal treatment centre as patients or attendants. SETTING: The International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh. SUBJECTS: An estimated 19,349 unimmunised women aged 15 to 45 and 17,372 children attending the centre for treatment or accompanying patients between 1 January and 31 August 1989. MAIN OUTCOME MEASURES: The number of women and children who were unimmunised or incompletely immunised was calculated and the percentage of this target population accepting vaccination was recorded. RESULTS: 7530 (84.2%) Of 8944 eligible children and 7730 (40.4%) of 19,138 eligible women were vaccinated. Of the children, 63.8% were boys, 75.9% were aged under 1 year, and 23.0% were aged 1 to 2 years. The estimated number of missed opportunities for vaccination was 716 among the children (8.0% of the target population) and 11,408 among the women (59.6% of those eligible). CONCLUSION: It is possible to establish immunisation services at a health facility treating acutely ill patients. PMID- 2242459 TI - ABC of major trauma. Major maxillofacial injuries. PMID- 2242460 TI - Resuscitation of patients with cardiac arrest by ambulance staff with extended training in West Yorkshire. AB - OBJECTIVE: To investigate the results of resuscitation of patients with cardiac arrest by ambulance staff with extended training in West Yorkshire. DESIGN: Study of all such attempts at resuscitation over 32 months, based on the standard report form for each call made by the ambulance staff and the electrocardiogram that showed the initial rhythm in each patient. SETTING: Area covered by West Yorkshire ambulance service. SUBJECTS: 1196 Patients with cardiac arrests attended by 29 ambulance staff with extended training. MAIN OUTCOME MEASURE: Result of resuscitation. RESULTS: The initial rhythm was asystole or electromechanical dissociation in 740 patients and ventricular fibrillation in 456 patients; overall 65 patients survived to be discharged from hospital. Sixty four of the 456 patients in whom ventricular fibrillation was the initial rhythm recorded, and 46 in whom ventricular fibrillation persisted after the ambulance staff arrived, survived. Only one of the 740 patients who initially had asystole or electromechanical dissociation survived. Factors associated with a greater chance of ventricular fibrillation occurring were: age less than 71, the arrest being witnessed by a bystander, resuscitation by a bystander, the arrest occurring in a public place, and a response time by the ambulance staff of less than six minutes. For patients found in ventricular fibrillation a shorter response time was associated with improved survival but resuscitation by a bystander was not. Additional skills learnt during extended training were used for 51 of the 65 patients who survived. CONCLUSIONS: Ambulance staff with extended training can save the lives of patients with cardiac arrest due to fibrillation, though asystole and electromechanical dissociation have a poor prognosis and should perhaps receive little attention during extended training. PMID- 2242461 TI - Dangers of neonatal intubation with the Cole tube. PMID- 2242462 TI - Population registers and public health. PMID- 2242463 TI - Sleep disorders in children. PMID- 2242464 TI - Impact of HIV on tuberculosis in Zambia. PMID- 2242466 TI - The Black report. PMID- 2242465 TI - Is antenatal selection for spina bifida possible? PMID- 2242467 TI - Management of severe burns. PMID- 2242468 TI - Occult ischemic necrosis of skeletal muscle. PMID- 2242469 TI - Whiplash injury. PMID- 2242470 TI - Terminal cancer care and patients' preference for place of death. PMID- 2242471 TI - Race and ethnicity in the European context. PMID- 2242472 TI - Chronic anaemia, hyperbaric oxygen and tumour radiosensitivity. AB - Anaemia is an important factor in the response of some human tumours to radiotherapy. The outcome is also influenced by whether the treatment is given in air or high pressure oxygen (HPO). The present study examined the relationship between anaemia and tumour response to radiation given in air or HPO in C3H mice transplanted with a mammary adenocarcinoma using a growth delay assay to assess the radiation response. Chronic anaemia was induced by the use of a low iron diet and was characterized by a significant reduction in host haematocrit and whole blood viscosity. In addition, anaemia was associated with a right shift in the oxyhaemoglobin dissociation curve and an increase in the volume doubling time of the tumour; but there was no change in the concentration of 2,3 diphosphoglycerate in the red cells. Radiation studies with these anaemic mice demonstrated that the tumour radiosensitivity was decreased when treatment was given in air. HPO was successful in overcoming the increased radioresistance associated with anaemia. This result suggested that tumours grown in anaemic mice have a higher hypoxic fraction than those grown in control mice. Changes in host physiology with chronic anaemia may contribute to the benefit seen with HPO but such alterations per se may be inadequate to maintain tumour oxygenation when treatment is given in air. PMID- 2242473 TI - The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues in the pig. II. Late effects on cutaneous and subcutaneous tissues. AB - The late effects of irradiation with single and fractionated doses of X rays (250 kV) and fast neutrons (42 MeVd----Bc), on the cutaneous and subcutaneous tissues of the pig, have been evaluated from measurements of changes in relative field length. These were determined at intervals of 26-104 weeks after irradiation. For fractionated irradiation with X rays the average fractions exponent, N, obtained from a log-log plot of iso-effect dose (ED50) against fraction number was 0.41. This was independent of the period of assessment, with no significant indication of a time factor. However, the exponent N did vary with the level of effect and was in the range 0.33-0.51. It was greatest for a greater than or equal to 10% reduction in relative field length. Assuming the validity of the linear quadratic model of cell survival, the alpha/beta ratio was 1.95 Gy. However, this model fitted the data less well for the least severe levels of damage, and for these the alpha/beta ratios were not significantly different from zero. Irradiation with fast neutrons showed a small effect of fractionation for doses given in greater than or equal to 6 fractions compared with a single dose. There was no significant increase in iso-effect dose when the dose was given in 30 fractions compared with 6 fractions. The relative biological effectiveness for late cutaneous and subcutaneous damage for the energy of fast neutrons used did not vary with the period of assessment, i.e. 26-52 weeks compared with 65-104 weeks, and was not significantly different from that previously obtained for ischaemic dermal necrosis, seen after higher doses, at 12-20 weeks after irradiation. PMID- 2242474 TI - Quantitative gamma-ray computed tomography of the radius in normal subjects and osteoporotic patients. AB - A new design of gamma-ray computed tomography (CT) scanner was used to measure bone density in 516 normal adults and in 116 female patients with osteoporotic fractures. Trabecular bone density (TBD) was measured for a core of the ultradistal radius; cortical bone mass per unit length (MLS) and mass per unit volume (MVS) were computed for the radius shaft. TBD, MLS and MVS peaked at the age of about 40 in females and fell by 32%, 15% and 24%, respectively, by the age of 65. In males, TBD decreased from the third decade and MLS and MVS peaked in the fourth decade. The corresponding falls by 65 years were 20%, 6% and 7%. In patients with Colles' fracture TBD and MLS were reduced by 13% and 10%, respectively, relative to age matched normal female subjects. For patients with vertebral crush fracture the reductions relative to age matched normal females were 36%, 17% and 16% for TBD, MLS and MVS. In fracture patients the deficit in TBD was significantly greater than that for cortical bone but TBD was no better at discriminating normal and osteoporotic individuals because of its larger normal range. We conclude that gamma-ray CT may best be used for monitoring changes in bone rather than as a diagnostic screening tool. PMID- 2242475 TI - Choroid plexus cysts and chromosomal defects. AB - During a 4-year period, 83 pregnant women with fetal choroid plexus cysts were investigated in our unit. Abnormal karyotypes were found in 20 fetuses, including trisomy 18 (n = 16), trisomy 13 (n = 1), triploidy (n = 1) and translocation Down's syndrome (n = 2). All fetuses with chromosomal defects had structural malformations in addition to the choroid plexus cysts. PMID- 2242476 TI - Ultrasonography in patients with suspected acute appendicitis: a prospective study. AB - The diagnostic accuracy of high-resolution real-time ultrasonography was prospectively studied in 240 patients admitted to the hospital with suspected acute appendicitis. The criteria for ultrasound diagnosis of appendicitis included a sausage-shaped, aperistaltic, hypoechoic structure when imaged along its longitudinal axis, with a target-like appearance on transverse section. The ultrasonographic findings were correlated with surgical-pathological outcome in 82 cases with proven appendicitis, with laparotomy findings in another 21 patients and with clinical follow-up in the remainder. The overall sensitivity, specificity and accuracy of ultrasonography in the diagnosis of acute appendicitis were 78%, 92% and 87%, respectively. The positive predictive value was 84% and the negative predictive value was 88%. Ultrasonography may significantly improve the diagnostic accuracy in patients with suspected acute appendicitis and should be performed in all patients in whom the clinical diagnosis is equivocal. The ultrasonographic findings must be interpreted in light of the clinical findings. PMID- 2242477 TI - Sedation in children scanned with high-field magnetic resonance; the experience at the Hospital for Sick Children, Great Ormond Street. AB - Patient movement is the most common cause of image degradation when performing magnetic resonance scans in children. This is a particular problem scanning at high field, as noise levels of up to 90 dB may be reached. Movement can be reduced by adequate sedation. We present the results of two sedation protocols when scanning with a 1.5T Magnetom scanner. Optimal scan quality can be achieved in up to 85% of scans using Pethco combined with triclofos in children aged 1 month-2 years, and trimeprazine combined with papaveretum in children over 2 years. When heavy sedation is used, patient selection must be cautious, and there is a minimum acceptable level of monitoring including close physical observation, electrocardiographic and apnoea monitoring. PMID- 2242478 TI - A man with three knees? False "hot spot" with dual isotope imaging. PMID- 2242479 TI - Additive filtering. PMID- 2242480 TI - Computerized calculation of radiation dose to patients from radiography. PMID- 2242481 TI - Progressive systemic sclerosis (diffuse scleroderma) and radiotherapy. PMID- 2242482 TI - Spinal cord sarcoidosis with intramedullary cyst formation. PMID- 2242483 TI - Ultrasonic appearances of the early changes in fibrodysplasia ossificans progressiva. PMID- 2242484 TI - Cystic lymphangioma of the pelvis in childhood. PMID- 2242485 TI - Unusual presentation of non-Hodgkin's lymphoma of the small bowel. PMID- 2242486 TI - Ultrasound appearances of extramedullary haematopoiesis in the liver and spleen. PMID- 2242487 TI - A case of post-operative paresis. PMID- 2242488 TI - Mathematical models of repopulation and reoxygenation in radiotherapy. PMID- 2242489 TI - Contrast medium inhibition in osteoarthritic cartilage. PMID- 2242490 TI - Fracture risk: a role for compact bone. PMID- 2242491 TI - Long-term observations of vertebral fractures in spinal osteoporotics. AB - The changes in the number and distributions of vertebral fractures were studied from the long-term observations (average 7 years) of 21 spinal osteoporotic patients. Distribution of wedge fractures was biphasic with peak frequencies at the midthoracic and thoracolumbar spine. Biconcave fractures occurred predominantly in the lumbar spine. These patterns of distribution did not change during the period of observation. The rate of biconcave fracture increased, the rate of wedge fracture decreased, and that of collapse remained the constant in follow-up. The changes in the number of fractures were divided into three types: increasing, plateau, and unchanged type. With the advance of osteoporosis, the increasing type was considered to change into the plateau type, which is probably the terminal stage of spinal osteoporosis. The unchanged type, in contrast, was distinct from the other two types because of increased spinal bone mineral density and decreased urinary calcium, which suggests that spinal osteoporosis is heterogeneous with regard to calcium metabolism. PMID- 2242492 TI - Effects of salmon calcitonin on the bone loss induced by ovariectomy. AB - We present the results of a 12-month clinical study assessing the effects of synthetic salmon calcitonin (sCT) on a group of fertile white women who had undergone ovariectomy for uterine fibromatosis. The study was performed to verify whether CT can prevent the loss of bone mass and the changes in calcium phosphorus metabolism associated with acute estrogen deficiency. The study consisted of an initial double-blind phase of 6 months, followed by a 6-month open period. Treated patients were given 100 MRC U of synthetic salmon CT injected i.m. in the morning, every other day, starting on the 7th day after the operation and continued for 12 months. Control patients received a placebo injection for the first 6 months; subsequently, they too were treated with sCT i.m. every other day for 6 months at the same dose as the 12 month-treated group. All patients received 500 mg of elementary calcium p.o., b.i.d. Bone mineral content (BMC) was measured at the extreme distal radius of the nondominant arm by a dual photon bone densitometer which utilizes two radio nuclides, 241 Am and 125 I, with energies of about 60 and 30 KeV. Biochemical parameters of the calcium phosphorus metabolism were also measured. After 12 months of study, no significant changes of BMC were observed in the 12 months sCT treated group, while control patients, treated 6 months after the ovariectomy, showed a significant decrease in BMC values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242493 TI - Vertebral cortical bone mass measurement by a new quantitative computer tomography method: correlations with vertebral trabecular bone measurements. AB - Previous studies comparing axial and appendicular skeleton have shown that trabecular bone loss is greater than cortical bone loss. However, whether the same difference exists between the trabecular and the cortical compartments of the vertebral body remains to be determined. In this study, we used quantitative computer tomography (QCT) to simultaneously measure the cortical rim of the vertebral body as well as trabecular bone. In 99 Caucasian women (mean age 53.8 +/- 13.0 years, range 26-79 years) we found a significant correlation between cortical mineral content (BMCC) and both single (SE) and dual energy (DE) trabecular mineral content (BMCT) (r = 0.62, P less than 0.0001 for both regressions). The cross-sectional rates of bone loss per year were 1.32%, 1.16%, and 0.59% for SE-BMCT, DE-BMCT, and BMCC, respectively. BMCC decreased at a rate that was 45-51% that of SE-BMCT and DE-BMCT, respectively. Our results indicate that (1) QCT may provide a useful means to selectively measure cortical density in vertebral bodies; (2) the decrease of cortical density over time in the spine appears to have been underestimated previously by extrapolation from appendicular bone measurements; (3) because measurements of the entire vertebral body (exclusive of the posterior elements) may provide information that is more representative of spine changes with age, a measurement that includes both areas might be more useful than one measuring only the trabecular region. PMID- 2242494 TI - Sodium fluoride does not increase human bone cell proliferation or protein synthesis in vitro. AB - The efficacy of sodium fluoride therapy for osteoporosis remains controversial. Evidence from clinical studies and from animals receiving fluoride has suggested that fluoride might act on bone to increase osteoblast numbers and matrix synthesis. In order to examine the hypothesis that fluoride has a direct mitogenic or anabolic action on the osteoblast, we tested the effect of fluoride on first passage human osteoblastic bone cells grown from collagenase-treated trabecular bone fragments. Under a variety of culture conditions, including both medium supplementation with serum and with a chemically defined medium, fluoride in doses ranging from 10(-6) to 10(-3) M did not alter cell proliferation as measured either by thymidine incorporation or by direct cell counting. Furthermore, exposure to fluoride under conditions of low serum supplementation did not alter either the total protein synthesis of the cells or their biosynthetic profile. These data suggest that fluoride does not act in vitro upon differentiated osteoblastic bone cells derived from adult human patients. PMID- 2242495 TI - Effect of 1,25(OH)2D3 and 24,25(OH)2D3 on calcium ion fluxes in costochondral chondrocyte cultures. AB - Vitamin D3 metabolites have been shown to affect proliferation, differentiation, and maturation of cartilage cells. Previous studies have shown that growth zone chondrocytes respond primarily to 1,25(OH)2D3 whereas resting zone chondrocytes respond primarily to 24,25(OH)2D3. To examine the role of calcium in the mechanism of hormone action, this study examined the effects of the Ca ionophore A23187, 1,25(OH)2D3, and 24,25(OH)2D3 on Ca influx and efflux in growth zone chondrocytes and resting zone chondrocytes derived from the costochondral junction of 125 g rats. Influx was measured as incorporation of 45Ca. Efflux was measured as release of 45Ca from prelabeled cultures into fresh media. The pattern of 45Ca influx in unstimulated (control) cells over the incubation period was different in the two chondrocyte populations, whereas the pattern of efflux was comparable. A23187 induced a rapid influx of 45Ca in both types of chondrocytes which peaked by 3 minutes and was over by 6 minutes. Influx was greatest in the growth zone chondrocytes. Addition of 10(-8)-10(-9) M 1,25(OH)2D3 to growth zone chondrocyte cultures results in a dose-dependent increase in 45Ca influx after 15 minutes. Efflux was stimulated by these concentrations of hormone throughout the incubation period. Addition of 10(-6)-10(-7) M 24,25(OH)2D3 to resting zone chondrocytes resulted in an inhibition in ion efflux between 1 and 6 minutes, with no effect on influx during this period. Efflux returned to control values between 6 and 15 minutes. 45Ca influx was inhibited by these concentrations of hormone from 15 to 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242496 TI - Orientation of apatite and organic matrix in Lingula unguis shell. AB - The orientation relationship between apatite and organic matrix in shell of Lingula unguis (inarticulate brachiopod) was studied. The organic layers, mineralized layers, and decalcified mineralized layers were examined layer by layer using microbeam X-ray diffraction technique. Both organic layer and decalcified mineralized layer showed the diffraction pattern of beta-chitin. The degree of orientation of apatite showed correlation to that of beta-chitin: Well oriented diffraction patterns of apatite crystal and organic matrix were observed in the central part. In this part, the fiber axis of beta-chitin was parallel to the c-axis of apatite. A close relationship of unit cell dimension between apatite and chitin was indicated. These strongly suggest that the fibrous structure of organic matrix assists the orientation of apatite crystals in Lingula unguis shell. PMID- 2242497 TI - Effect of ovariectomy and prednisolone on bone mineral content in rats: evaluation by single photon absorptiometry and radiogrammetry. AB - The effects of ovariectomy and prednisolone were studied for 9 months in 3-month old rats on a moderately low calcium diet. Measurements were made by single photon absorptiometry of the femur at cortical and trabecular bone sites. Radiogrammetry was performed at the midshaft of the femur. During growth, body weight, bone size, and bone mineral content (BMC) increased in male rats more than in females. After ovariectomy, body weight increase was more pronounced, but bone mineral increase was lower than in controls. At the distal end of the femur, bone mineral density decreased after 3 months, and at the midshaft of the femur, medullary width increased significantly from 6 months on. Prednisolone in a dose of 0.5 mg/kg/day did not influence BMC. However, prednisolone treatment after ovariectomy induced a more pronounced effect on bone than ovariectomy alone. BMC increase was lower than in ovariectomy, and bone mineral density decreased significantly, especially at the distal end of the femur. After correction for differences in body weight, globally the same results were found. We conclude that (1) the combination of single photon absorptiometry and radiogrammetry allows the evaluation of growth and the effect of ovariectomy and prednisolone treatment in rats; (2) ovariectomy results in bone loss first at the distal end and later in the midshaft of the femur; (3) prednisolone in a dose of 0.5 mg/kg/day alone did not affect bone mass; and (4) prednisolone profoundly enhanced the effects of ovariectomy. PMID- 2242498 TI - Calcitonin on osteoporotic bone fragility. PMID- 2242499 TI - Serum calcium in diabetes. PMID- 2242500 TI - Role of endogenously produced interleukin-6 as a second signal in murine thymocyte proliferation induced by multiple cytokines: regulatory effects of transforming growth factor-beta. AB - Previous studies have demonstrated that murine thymocytes proliferate in the presence of submitogenic concentrations of phytohemagglutinin-P (PHA-P) and various cytokines such as interleukin-1 (IL-1), interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). We report that C3H/HeJ thymocytes stimulated with PHA-P and IL-1, IL-4, or TNF-alpha secrete significant levels of IL-6 as determined on B9 hybridoma cells. The possibility that thymocyte proliferation induced by these cytokines was mediated through IL-6 was investigated utilizing a neutralizing monoclonal antibody against murine IL 6, MP5 20F3.1. The results demonstrate that MP5 20F3.1 inhibited the proliferative response of thymocytes and B9 hybridoma cells to recombinant MuIL-6 (but not HuIL-6) and neutralized the endogenous IL-6 produced in the thymocyte cultures, but did not have any measurable effects on the proliferative responses induced by IL-1, IL-4, or TNF-alpha. Although the level of endogeneously produced IL-6 did not play a measurable role in the proliferative response induced by TNF alpha, the addition of higher concentrations of IL-6 augmented the proliferation of murine thymocytes induced by rMu TNF-alpha. In addition, recombinant human transforming growth factor-beta 1 (rHu TGF-beta 1) significantly inhibited thymocyte proliferation induced by HuIL-1, rMuIL-4, rMuIL-6, and rMuTNF-alpha. The studies suggest that IL-1, IL-4, or TNF-alpha mediate a proliferative signal on murine thymocytes independent of IL-6 and that the proliferative signals provided by these cytokines as well as IL-6 are inhibitable by rHu TGF-beta 1. PMID- 2242501 TI - Culture and characterization of thymic epithelium from autoimmune NZB and NZB/W mice. AB - Autoimmune NZB and NZB/W mice display early abnormalities in thymus histology, T cell development, and mature T cell function. Abnormalities in the subcapsular/medullary thymic epithelium (TE) can also be inferred from the early disappearance of thymulin from NZB. It has also been reported that NZB thymic epithelial cells do not grow in culture conditions that support the growth of these cells from other strains of mice. In order to study the contribution of TE to the abnormal T cell development and function in NZB and NZB/W mice, we have devised a culture system which supports the growth of TE cells from these mice. The method involves the use of culture vessels coated with extracellular matrix produced by a rat thymic epithelial cell line. TEA3A1, and selective low-calcium, low-serum medium. In addition TEA3A1 cells have been used as an antigen to generate monoclonal antibodies specific for subcapsular/medullary TE. These antibodies, as well as others already available, have been used to show that the culture conditions described here select for cells displaying subcapsular/medullary TE markers, whereas markers for cortical TE and macrophages are absent. PMID- 2242502 TI - Stimulation of human interleukin 1 production and specific mRNA expression by microtubule-disrupting drugs. AB - The production of interleukin 1 (IL1), a pleiotropic monocyte-derived interleukin, can be induced in vitro by various stimuli. The present study shows that cytochalasins which inhibit actin filament polymerization in various cell types have no significant effect on IL1 production from human monocytic cells. On the contrary, microtubule disrupters such as colchicine, vinblastine, and vincristine dramatically potentiate (15- to 35-fold), in a dose-dependent fashion, cell-associated IL1 and to a lesser extent (2.5- to 7-fold) released IL1 in the myelomonocytic THP1 cell line and in adherent peripheral blood mononuclear cells. The enhancing effect of the drugs was blocked by actinomycin D and by cycloheximide and was accompanied by an increase of specific IL1 beta mRNA expression as measured by Northern blot analysis, thus indicating that these drugs act at a transcriptional or post-transcriptional IL1 gene expression level. PMID- 2242503 TI - Expression of cellular effector functions and production of reactive nitrogen intermediates: a comparative study including T lymphocytes, T-like cells, neutrophil granulocytes, and mononuclear phagocytes. AB - The ability of various cell types to secrete reactive nitrogen intermediates (RNI) upon functional activation was comparatively assessed. Neither in T lymphocyte clones mediating MHC class I or class II antigen-restricted killing via alpha/beta T cell receptor (TcR) or MHC-unrestricted killing via gamma/delta TcR, nor in peripheral blood mononuclear cells expressing natural killer or lymphokine-activated killer activity, target cell lysis was associated with detectable RNI production. Also, activated neutrophil granulocytes did not secrete RNI. In contrast, bone marrow-derived mononuclear phagocytes, activated to express tumoricidal activity, secreted marked RNI activity. PMID- 2242504 TI - Influence of age on the rhythm in basal and forskolin-stimulated adenylate cyclase activity of the rat heart. AB - In male rats of three different ages (Group I: 7 weeks, Group II: 4 months, Group III: greater than 10 months) basal and forskolin-stimulated adenylate cyclase (AC) activity were investigated in rat heart ventricles of animals sacrificed at 8 time points within 24 hours of a day. Maximum (Emax) and half-maximum (EC50) stimulation by a water-soluble forskolin (FOR; 0.1-100 mumol/l) were determined from dose-response curves. In young rats (Group I) significant rhythmicity was found in basal and FOR-stimulated AC activity, which was successively reduced or abolished with age by a reduction in amplitude. Mean basal AC activity increased about 2-fold from Group I to Group II/III. Mean maximum in FOR stimulation was about 12-fold in Group I and about 7-fold in Group II and III. EC50-values displayed neither a significant rhythmicity in either group nor an age dependency. It is concluded that the stimulatory potency of the catalytic subunit of the AC is reduced with age. PMID- 2242505 TI - Effect of chronic caloric restriction on the synchronization of various physiological measures in old female Fischer 344 rats. AB - A variety of physiological and behavioral parameters which relate to metabolism were continuously monitored in 18 month old female Fischer 344 rats which were maintained on either ad libitum or reduced calorie diets. Caloric restriction (CR) stimulated average motor activity per day, the duration of each feeding episode, food consumed per episode, and water consumed per gram lean body mass (LBM). However, CR limited total food consumption, feeding time, number of feeding episodes per day, total eating and drinking time, and the daily ratio of food consumed to water consumed, CR also decreased average body temperature per day, O2 consumption, CO2 production, and respiratory quotient. A variety of parameters concerning water consumption were not affected. CR rats ate their food immediately when food was presented during the light span, while ad libitum fed animals ate numerous small meals throughout the entire dark span. An anticipatory response to restricted feeding was also noted. Total motor activity, metabolism, and body temperature increased just prior to scheduled feeding and reached maximum values shortly after feeding, suggesting that these parameters were highly synchronized to feeding. Females and males were found to respond to caloric restriction in a similar fashion. Dramatic changes in respiratory quotient and body temperature suggest rapid shifts between metabolic pathways (glycolysis to gluconeogenesis) to obtain optimal efficiency. Lower body temperature and metabolism may provide protection against DNA damage, thereby increasing the survival potential of restricted rats. These responses may provide insight into the mechanisms by which caloric restriction acts to extend life span. PMID- 2242507 TI - Diurnal variations of beta-endorphin at rest and after moderate intensity exercise. AB - To determine the effect of time of day on circulating beta-endorphin concentrations 14 men exercised at 75% of their maximal capacity at 0600, 1200, 1800 and 2400 hr. Each trial was separated by 3-5 days and preceded by a normal sleep cycle except for the 0600 hr trials which was preceded by 6 hr sleep. Resting physiological data indicated normal diurnal variations in heart rate, core temperature and oxygen uptake, being lowest during the 0600 hr trials and highest during the 1800 hr trials. Resting plasma beta-endorphin concentrations averaged 11.9 +/- 8.4 pmol/l during the 0600 hr trials, significantly greater than the 2400 hr trials (6.4 +/- 3.6 pmol/l; P less than 0.05). No other significant differences existed at rest. Post exercise beta-endorphin concentrations were elevated and found to be inversely related to time of day with the 0600 hr trials having the highest mean (25.7 +/- 14.7) and the 2400 hr trials the lowest (14.7 +/- 8.3). These data suggest that the plasma beta endorphin concentrations at rest and after exercise are affected by the time of day. The results also suggest that the changes in beta-endorphin associated with exercise are not major contributors to cardiorespiratory control or changes in psychological effect associated with exercise. PMID- 2242506 TI - Actigraphy: a means of assessing circadian patterns in human activity. AB - Twenty-three diurnally active (0705-2333), healthy persons between 22 and 54 years of age and without history of sleep abnormality were monitored continuously for 120 consecutive hr (five days) by wrist actigraphy. Circadian rhythms of high amplitude were detected by cosinor analysis for each participant and for the groups of 10 males and 13 females with the average span of heightened activity timed between approximately 1330 and 1605. The circadian peak-trough difference in wrist movement was marked, equalling approximately 75% of the 24-hr mean level. In 19 of 23 participants, the 24-hr mean of wrist activity varied between 140-180 movements/min, with four persons exhibiting lesser means of 110-140 movements/min. With respect to the daytime span of activity, the mean wrist movement of individual participants ranged from 155-265 movements/min, with the majority (20/23) varying between 185-245 movements/min. During nocturnal sleep the mean wrist activity level was quite low, varying between individuals from 5 to 25 movements/min for 21 of 23 persons. Wrist actigraphy proved to be well accepted and was a most reliable means of monitoring aspects of body movement during activity and sleep in ambulatory persons adhering to usual life habits and pursuits. PMID- 2242508 TI - Circadian variation in human performance evaluated by the Walter Reed performance assessment battery. AB - As part of a two clock-time (0830 versus 2030) evaluation of administration-time dependent effects of dexedrine (5 mg) and triazolam (0.25 mg) on human cognitive performance, placebo (control) studies were conducted on 12 diurnally active (0700-2300) male adults (23-38 yrs) using a double-blind, randomized crossover design. Testing was conducted hourly during a series of sleepless 13-hr spans commencing in the morning or evening, using the Walter Reed computer controlled and scored multi-task cognitive performance assessment battery. For the placebo condition, Single and Group Cosinor analyses documented circadian rhythms in performance for most tasks (reaction time, logical reasoning, serial add/subtract and spatial orientation) both for individuals and the group. Overall, performance was worse overnight, when sleepiness was greatest, and best between 1830 and 2030. It was most variable around 0600-0700. The day-night variation in performance over all cognitive tests amounted to 21% of the 24-hr mean. PMID- 2242509 TI - Shiftwork and industrial injuries at a chemical plant in southeast Texas. AB - A historical retrospective study of 242 shiftworker (SW) and 224 non-SW (NSW) injuries at a chemical manufacturing plant in southeast Texas (U.S.A.) was performed. Data were collected on injuries that occurred between 1 January 1982 and 31 December 1985. The SW schedule comprised an 8-hr, 7-day backward rotation program while the dayworker schedule consisted of a typical U.S.A. 40-hr work week. Injury records were matched against payroll/attendance records to substantiate the probability of isolating possible effects of the shiftwork rotation schedule on the rates, distribution and severity of injuries. Injuries in the SW sample were compared to those in the non-SW sample. The work responsibilities of dayworkers were not exactly the same as those of shiftworkers. However, the job responsibilities for males and females within the dayworker and shiftworker groups were equivalent. Overall injury incidence rates were not significantly different between SWs and non-SWs, although female SWs had significantly higher incidence rates than did male SWs and both male and female dayworkers. The occurrence of injuries, however, was not equally distributed during the day shift and the night shift, but was equally distributed during the evening shift and for non-SWs, suggesting that certain, yet to be determined, factors were affecting the distribution of injuries during the day and night shift. However, the average number of injuries was two-three times higher during the first four days of the day and night shift, yet were not elevated during the evening shift. PMID- 2242511 TI - A simple method for testing monthly statistical rates for normalization. PMID- 2242510 TI - Early onset and accumulation of REM sleep in depression: a study of the phase advance hypothesis. AB - Twenty-two depressed subjects who met criteria for major depressive disorder were grouped according to their initial REM latency. Subjects with short (less than or equal to 60 min) initial REM latency were separated from those with normal (greater than 60 min) initial REM latency. Subjects with short initial REM latency were found to have earlier onsets to at least two subsequent REM periods. The number of minutes of REM sleep accumulated were also plotted against elapsed time after sleep onset. The short-latency group accumulated REM sleep earlier than, but at about the same rate as, the normal latency group. These data support the phase-advance hypothesis of REM sleep in depression. PMID- 2242512 TI - Chronophysiology and ambulatory monitoring instrumentation. PMID- 2242513 TI - Continuous darkness stimulates body growth of the juvenile giant freshwater prawn, Macrobrachium rosenbergii de Man. AB - The effect of photoperiod on growth of juvenile giant freshwater prawns, Macrobrachium rosenbergii de Man, was tested. The prawns were divided into four groups and each group was reared under one of the following light-dark conditions: continuous darkness (L0:D24), 12 hr light: 12 hr dark (L12:D12), 16 hr light: 8 hr dark (L16:D8), and 20 hr light: 4 hr dark (L20:D4). Body size was determined at the age of 45, 75, and 110 days by measuring total length, orbital length, and carapace length; body weight was determined at the age of 110 days. At 110 days of age, the prawns reared under L0:D24 photoperiod were significantly longer and heavier than those reared under other light-dark conditions. The survival rate of the prawns reared under L0:D24 photoperiod was also higher than that of other groups. This study indicates a positive effect of continuous darkness on growth and survival rate of juvenile giant freshwater prawns, M. rosenbergii. PMID- 2242514 TI - Current status of antitachycardia devices. AB - With the limitations of currently available modalities for treating clinically important tachycardias, the role of implanted antitachycardia devices will continue to expand. The challenge of the future will not only involve continued technological advances but the socioeconomic impact of this efficacious but expensive mode of therapy in an era of increasing financial restraints. Further studies to definitively prove the efficacy of more widespread use of antitachycardia device therapy will be needed. PMID- 2242515 TI - Pathophysiological insights into the cardiomyopathy of Chagas' disease. AB - The evidence gained from both human and animal studies of chronic chagasic cardiomyopathy suggests that the disease occurs as a consequence of several discrete and progressive pathophysiological processes occurring after infection, the ultimate expression of which depends on a host of unidentified factors. Collectively, the infection-associated events compromise microvasculature function and result in hypoperfusion, with consequences indistinguishable from those observed in other, nonparasitological cardiomyopathic diseases secondary to hypoperfusion. Therefore, chronic chagasic cardiomyopathy may share similar pathophysiological abnormalities with other chronic congestive cardiomyopathic states. PMID- 2242516 TI - Catheterization laboratory events and hospital outcome with direct angioplasty for acute myocardial infarction. AB - To assess the safety of direct infarct angioplasty without antecedent thrombolytic therapy, catheterization laboratory and hospital events were assessed in consecutively treated patients with infarctions involving the left anterior descending (n = 100 patients), right (n = 100), and circumflex (n = 50) coronary arteries. The groups of patients were similar for age (left anterior descending coronary artery, 59 years; right coronary artery, 58 years; circumflex coronary artery, 62 years), patients with multivessel disease (left anterior descending coronary artery, 55%; right coronary artery, 55%; circumflex coronary artery, 64%), and patients with initial grade 0/1 antegrade flow (left anterior descending coronary artery, 79%; right coronary artery, 84%; circumflex coronary artery, 90%). Cardiogenic shock was present in eight patients with infarction of the left anterior descending coronary artery, four with infarction of the right coronary artery, and four with infarction of the circumflex coronary artery. Major catheterization laboratory events (cardioversion, cardiopulmonary resuscitation, dopamine or intra-aortic balloon pump support for hypotension, and urgent surgery) occurred in 10 patients with infarction of the left anterior descending coronary artery, eight with infarction of the right coronary artery, and four with infarction of the circumflex coronary artery (16 of 16 shock and six of 234 nonshock patients, p less than 0.001). There was one in-laboratory death (shock patient with infarction of the left anterior descending coronary artery).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242517 TI - An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence. AB - The primary aim of this study was to estimate the relation between cholesterol reduction and total mortality and coronary heart disease (CHD) incidence. Secondarily, the clinical issues of whether the efficacy of cholesterol lowering is dependent on the treatment modality, presence of CHD at baseline, or the simultaneous introduction of other interventions was explored. All randomized clinical intervention trials of cholesterol reduction were used in an overview analysis of total mortality rate and CHD incidence; analysis was performed with weighted linear regression. The trials include those that used primary and secondary intervention, diet and drugs, and single or multifactor design. Nineteen trials were analyzed for total mortality, and of the 19, 16 were analyzed for CHD incidence rate. Net difference in cholesterol change between study groups was used as the independent variable, and the three previously mentioned dichotomous design characteristics were used as additional independent variables. For every 1% reduction in cholesterol, an estimated 2.5% reduction in CHD incidence is indicated (95% CL: 1.1, 3.9). With regard to CHD drug trials tended toward better efficiency in cholesterol lowering than did dietary trials. With regard to total mortality, this efficiency was higher in secondary than in primary preventive trials. The efficiency was also somewhat dependent on the baseline cholesterol level. This study shows that cholesterol reduction is effective in lowering CHD incidence, but cholesterol reduction must be at least 8 9% to be effective in lowering total mortality. PMID- 2242518 TI - Intermittent claudication, heart disease risk factors, and mortality. The Whitehall Study. AB - In the Whitehall study, 18,388 subjects aged 40-64 years completed a questionnaire on intermittent claudication. Of these subjects, 0.8% (147) and 1% (175) were deemed to have probable intermittent claudication and possible intermittent claudication, respectively. Within the 17-year follow-up period, 38% and 40% of the probable and possible cases, respectively, died. Compared with subjects without claudication, the probable cases suffered increased mortality rates due to coronary heart disease and cerebrovascular disease, but the mortality rate due to noncardiovascular causes was not increased. Possible cases demonstrated increased mortality rates due to cardiovascular and noncardiovascular causes. This difference in mortality pattern may be due to chance. Possible and probable cases still showed increased cardiovascular and all cause mortality rates after adjusting for coronary risk factors (cardiac ischemia at baseline, systolic blood pressure, plasma cholesterol concentration, smoking behavior, employment grade, and degree of glucose intolerance). Intermittent claudication is independently related to increased mortality rates. It is not a rare condition, and simple questionnaires exist for its detection. The latter can be usefully incorporated in cardiovascular risk assessment and screening programs. PMID- 2242519 TI - Sotalol versus quinidine for the maintenance of sinus rhythm after direct current conversion of atrial fibrillation. AB - This open, parallel-group study compares quinidine and sotalol treatment for maintenance of sinus rhythm after direct current conversion of patients with chronic atrial fibrillation. The patients from 15 centers in Sweden were randomized to sotalol (98 patients) or quinidine (85 patients) after 2 hours of sinus rhythm after direct current conversion. According to primary efficacy assessment, 52% of the patients in the sotalol group and 48% of the patients in the quinidine group remained in sinus rhythm during the following 6-month treatment period (NS). Furthermore, 34% of the patients treated with sotalol and 22% of the patients treated with quinidine relapsed into atrial fibrillation (NS). Heart rate after relapsing into atrial fibrillation was higher in the patients treated with quinidine (109 beats/min) than in the patients treated with sotalol (78 beats/min, p less than 0.001). Patients treated with sotalol were found to be less symptomatic at the time of relapse compared with relapsing patients in the quinidine group. In terms of safety, more patients were withdrawn from quinidine than from sotalol treatment (26% vs. 11%, p less than 0.05), and sotalol was generally better tolerated than quinidine. Twenty-eight percent of the patients treated with sotalol and 50% of the patients treated with quinidine reported side effects (p less than 0.01). The difference was primarily a result of early (within the first month of treatment) gastrointestinal and skin side effects in the group of patients treated with quinidine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242520 TI - A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis. AB - To determine whether calcium channel blockers influence the progression of coronary atherosclerosis, 383 patients age 65 years or less with 5-75% stenoses in at least four coronary artery segments were selected at random within 1 month of coronary arteriography to participate in double-blind therapy with a placebo or nicardipine 30 mg three times daily. Coronary events (5 deaths, 22 myocardial infarctions, and 28 unstable anginas) occurred in 28 of 192 nicardipine patients and 23 of 191 placebo patients (p = NS). At 24 months coronary arteriography was repeated in 335 patients. Progression, defined as a 10% or more worsening in diameter stenosis, measured quantitatively, was found in 147 of 1,153 lesions (12.7%) in 168 nicardipine patients and in 170 of 1,170 lesions (14.5%) in 167 placebo patients (p = NS). Ninety-two nicardipine patients (55%) and 95 placebo patients (57%) had progression at one or more sites (p = NS). Regression, that is, an improvement by 10% or more in diameter stenosis, was seen in 140 of 2,323 lesions (6.0%) overall, with no significant intergroup difference. Among the 217 patients with 411 stenoses of 20% or less in the first study, such minimal lesions progressed in only 15 of 99 nicardipine patients compared with 32 of 118 placebo patients (15% versus 27%, p = 0.046). In this subgroup, 16 of 178 minimal lesions in nicardipine patients and 38 of 233 minimal lesions in placebo patients progressed (p = 0.038). By stepwise logistic-regression analysis, baseline systolic blood pressure (p = 0.04) and the change in systolic blood pressure between baseline and 6 months (p = 0.002) correlated with progression of minimal lesions. This suggested blood pressure reduction may account for the beneficial action of nicardipine. These results suggested nicardipine has no effect on advanced coronary atherosclerosis but may retard the progression of minimal lesions. PMID- 2242521 TI - A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. AB - We performed a prospective, randomized, double-blind, crossover study to compare the efficacy and safety of vasodilation with the calcium entry blocker nifedipine with that of isosorbide dinitrate (ISDN) and their combination as treatment for heart failure. Twenty-eight patients with New York Heart Association Functional class II or III chronic heart failure due to left ventricular systolic dysfunction were studied. All patients were maintained on a constant dose of digitalis and diuretics throughout the study. Eight weeks of therapy with nifedipine alone or in combination with ISDN resulted in a significantly higher incidence of heart failure deterioration necessitating hospitalizations and/or additional diuretics. Twenty-four percent of patients required hospitalization during nifedipine therapy and 26% required hospitalization during nifedipine-ISDN combination therapy in comparison to 0% requiring hospitalization during ISDN therapy alone. The total number of heart failure-worsening episodes was nine among patients on nifedipine, three among patients on ISDN (p less than 0.09 versus nifedipine), and 21 among patients on nifedipine-ISDN combination (p less than 0.001 versus nifedipine, p less than 0.0001 versus ISDN). Premature discontinuation of drug administration due to clinical deterioration or other side effects occurred in 29% of patients during nifedipine therapy, 5% of patients during ISDN therapy (p = 0.05 versus nifedipine), and 19% of patients during the combination therapy. A comparison of eight patients who demonstrated clinical deterioration on nifedipine with the remainder of the patients demonstrated no significant difference in left ventricular ejection fraction (0.24 +/- 0.06 versus 0.23 +/- 0.07) or maximal oxygen uptake during exercise (13 +/- 3 versus 14 +/- 2 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242522 TI - Inotropic effects of angiotensin II on human cardiac muscle in vitro. AB - The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure. PMID- 2242523 TI - Functional chiral asymmetry in descending thoracic aorta. AB - To determine whether rotational blood flow or chiral asymmetry exists in the human descending thoracic aorta, we established the ability of color Doppler ultrasound to detect rotational flow in a tornado tube model of a vortex descending fluid column. In a model of the human aortic arch with a pulse duplicator, color Doppler was then used to demonstrate that rotational flow occurs first in the transverse arch and then in the proximal descending thoracic aorta. With the use of color Doppler esophageal echocardiography, 53 patients (age range, 25-78 years; mean age, 56.4 years) were prospectively examined for rotational flow in the descending thoracic aorta. At 10 cm superior to retro-left ventricular position, 22 of 38 patients (58%) revealed rotational flow with obvious diastolic counterclockwise rotation but less obvious systolic clockwise rotation. At 5 cm superior to retro-left ventricular position, 29 of 46 patients (63%) revealed rotational flow with a tendency toward systolic clockwise and diastolic counterclockwise rotation. At the retro-left ventricular position, 47 of 53 patients (89%) revealed rotational flow, usually of a clockwise direction, occurring in systole. Our data suggest that aortic flow is not purely pulsatile and axial but has a rotational component. Rotational flow begins in the aortic arch and is carried through to the descending thoracic aorta, where flow is chirally asymmetric with systolic clockwise and diastolic counterclockwise components. These data demonstrate an aortic rotational flow component that may have physiological implications for organ perfusion. PMID- 2242524 TI - Abnormal blood pressure response during exercise in hypertrophic cardiomyopathy. AB - To investigate the incidence of abnormal exercise blood pressure responses in hypertrophic cardiomyopathy (HCM) and the potential role of hemodynamic instability as a mechanism of sudden death, 129 consecutive patients with HCM underwent maximal symptom-limited treadmill exercise testing with blood pressure recording. Four patterns of blood pressure response were observed. Forty-three patients had significant exercise hypotension, with either a continuous fall in systolic blood pressure (n = 5) from the start of exercise or a sudden fall in systolic blood pressure (20-100 mm Hg; mean, 40 mm Hg) from the peak value (n = 38), 23 patients had a normal response during exercise but an abnormal blood pressure response in the recovery period, and the remaining 62 patients demonstrated a normal blood pressure response. Patients with exercise hypotension were younger (33 +/- 14 versus 46 +/- 14 years) and more of them had a family history of HCM and sudden death compared with those with a normal blood pressure response (15 of 43 versus 6 of 62 patients). Similarly, the 23 patients with abnormal recovery blood pressure responses were younger (43 +/- 16 versus 46 +/- 14 years) and had a higher incidence of a family history of sudden death (10 of 24 versus 6 of 62 patients). Left ventricular cavity dimensions were smaller in those with exercise hypotension, but 11 other clinical, echocardiographic, and arrhythmic variables were similar. To assess the mechanism of exercise hypotension, 14 patients who demonstrated exercise hypotension and 14 symptomatic patients with a normal exercise blood pressure response underwent invasive hemodynamic exercise testing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242525 TI - Airway hyperresponsiveness in patients with microvascular angina. Evidence for a diffuse disorder of smooth muscle responsiveness. AB - Anginal chest pain in patients with angiographically normal coronary arteries may be caused by a limited coronary flow response to stress because of abnormal function of the coronary microcirculation (microvascular angina). Studies of forearm arterial function suggested that patients with microvascular angina may have a diffuse disorder of smooth muscle tone. Because dyspnea is common in these patients and seems disproportionate to the severity of myocardial ischemia, we studied air flow (forced expiratory volume in 1 second, or FEV1) in the basal state and after methacholine inhalation to determine whether bronchial smooth muscle is affected in this syndrome. Five of 36 patients with microvascular angina had a basal FEV1 of less than 70% of that predicted and did not receive methacholine. Of the remaining 31 patients, 14 (45%) had a more-than-20% reduction in FEV1 after methacholine inhalation (as much as 25 mg/ml), a response significantly greater than that of nine patients with heart disease (0%, p less than 0.025) and 24 normal volunteers of similar age and gender distribution (13%, p less than 0.025). Furthermore, the product of the methacholine dose inhaled and the magnitude of decline in FEV1 from baseline (methacholine response score) was significantly lower in patients with microvascular angina than in normal volunteers (16 +/- 8.6 versus 22.2 +/- 3.7, p = 0.026). We conclude that airway hyperresponsiveness is frequently demonstrable in patients with microvascular angina; these findings are consistent with our hypothesis that this syndrome may represent a more generalized abnormality of vascular and nonvascular smooth muscle function. PMID- 2242526 TI - Prostacyclin and acetylcholine as screening agents for acute pulmonary vasodilator responsiveness in primary pulmonary hypertension. AB - Epoprostenol sodium (prostacyclin) administered intravenously is considered the standard for assessing the ability of the pulmonary circulation to vasodilate. At present, epoprostenol sodium is an investigational drug that has limited availability. In contrast, acetylcholine, also a pulmonary vasodilator, is readily available. Therefore, we assessed the feasibility of using acetylcholine as an alternative to prostacyclin in testing for the capacity of the pulmonary vasculature to vasodilate. Twenty-three patients with primary pulmonary hypertension (mean pulmonary arterial pressure, 58.5 +/- 13.4 mm Hg) received incremental infusions of prostacyclin and acetylcholine to predetermined maximal infusion rates as part of a battery of vasodilator agents administered according to standard protocols (mean, 5.4 +/- 1.2 agents/patient; range, 3-8 agents/patient); the administration of the different agents was timed to avoid synergistic effects. Of all the agents tested, prostacyclin and acetylcholine were most consistently effective in evoking acute pulmonary vasodilation, and both seemed to distinguish patients capable of manifesting acute pulmonary vasodilation from those who were not. However, at maximal doses set by protocol, prostacyclin generally elicited a greater vasodilator response than acetylcholine. The difference in magnitude of response may have been due to use of prescribed dosages of acetylcholine that were submaximal. In other respects, the two agents were similar; both were equally well-tolerated, and side effects were mild and resolved rapidly when the vasodilator infusions were stopped. We conclude that in the majority of patients with primary pulmonary hypertension, acetylcholine appears to be an effective and available substitute for prostacyclin in screening for pulmonary vasodilator responsiveness. PMID- 2242527 TI - Differentiation of ventricular tachyarrhythmias. AB - Implantable devices capable of several modes of therapy will require differentiation of various ventricular tachyarrhythmias. Three methods of arrhythmia analysis, magnitude-squared coherence, ventricular rate, and irregularity of cycle length were performed for 45 episodes of induced ventricular tachyarrhythmia in 15 patients. Differentiation of monomorphic ventricular tachycardia from polymorphic ventricular tachycardia and ventricular fibrillation was possible by mean magnitude-squared coherence, less possible by rate, and not possible by beat-to-beat irregularity. Faster monomorphic ventricular tachycardia overlapped with rates of polymorphic ventricular tachycardia and ventricular fibrillation. Differentiation of polymorphic ventricular tachycardia and ventricular fibrillation was not possible by rate or irregularity. A progressive decrease in mean magnitude-squared coherence from monomorphic ventricular tachycardia to polymorphic ventricular tachycardia to ventricular fibrillation strengthens previous observations that coherence is a measure of rhythm "organization." PMID- 2242528 TI - Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolic features. AB - The clinical, electrocardiographic, and coronary hemodynamic responses to sequential 90-second occlusions of the left anterior descending coronary artery in 12 patients undergoing elective percutaneous transluminal coronary angioplasty were examined. Transmyocardial lactate metabolism was examined in an additional group of seven patients with clinical and hemodynamic features similar to the first group. We noted that in comparison with the initial balloon occlusion the second occlusion was characterized by less subjective anginal discomfort, less ST segment shift (0.44 +/- 0.13 versus 0.21 +/- 0.07 mV, p = 0.01), and lower mean pulmonary artery pressure (25 +/- 1.0 versus 20 +/- 1.7 mm Hg, p = 0.005). In addition, for the same heart rate-blood pressure product, cardiac vein flow during the second inflation was significantly lower than that recorded during the first inflation (96 +/- 1.4 versus 83 +/- 2.4 ml/min, p = 0.005). Finally, there was significantly less myocardial lactate production during the second inflation (lactate extraction ratio: first inflation, -0.11 +/- 0.03; second inflation, 0.03 +/- 0.02; p = 0.04). We conclude that the lessened clinical, electrocardiographic, hemodynamic, and metabolic evidence of myocardial ischemia during the second of two periods of coronary artery occlusion during percutaneous transluminal coronary angioplasty supports the concept of adaptation to myocardial ischemia (ischemic preconditioning). PMID- 2242529 TI - Intracoronary urokinase for intracoronary thrombus accumulation complicating percutaneous transluminal coronary angioplasty in acute ischemic syndromes. AB - Intracoronary urokinase was used to treat flow-limiting intracoronary thrombus accumulation that complicated successful percutaneous transluminal coronary angioplasty (PTCA) during acute ischemic syndromes in 48 patients who were followed up through the acute phase of their illness. The study group comprised 10 patients with unstable angina pectoris, 18 patients with an evolving acute myocardial infarction, and 20 patients with postinfarction angina. The initial mean percent coronary diameter stenosis for the entire population was 95 +/- 7% and decreased with initial PTCA to 41 +/- 20% (p less than 0.001), with improved corresponding coronary flow by Thrombolysis in Myocardial Infarction trial (TIMI) grade. However, thrombus accumulation then resulted in a significant increase in percent diameter stenosis to 83 +/- 17% (p less than 0.001); a corresponding significant reduction in coronary flow also occurred by TIMI grade. After administration of intracoronary urokinase (mean dose, 141,000 units; range, 100,000-250,000 units during an average period of 34 minutes), with additional PTCA, mean percent diameter stenosis significantly decreased to 34 +/- 17% (p less than 0.001); a correspondingly significant improvement in mean coronary flow by TIMI grade occurred to 2.9 +/- 0.2. Overall, the angiographic success rate was 90%. There were no ischemic events requiring repeat PTCA and no procedure-related myocardial infarctions or deaths before hospital discharge. One patient was referred for urgent coronary artery bypass graft surgery after a successful PTCA. Plasma fibrinogen levels were obtained in 15 patients, and in no patient was the level below normal for our laboratory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242530 TI - Coronary atherosclerosis is associated with left ventricular dysfunction and dilatation in aortic stenosis. AB - Patients with aortic stenosis develop widely variable patterns of left ventricular hypertrophy and dysfunction. We postulated that coronary atherosclerosis (CAD) may be associated with impaired left ventricular function and chamber dilatation in patients with aortic stenosis. Left ventricular mass and volumes were quantified from two-dimensional echocardiography and correlated with coronary angiography in 78 patients with severe aortic stenosis and no previous myocardial infarction or regional wall motion abnormalities. Eighteen patients (group 1) had smooth coronary arteries, 25 patients had irregular coronary arteries with 50% or less stenosis (group 2), and 35 patients had obstructive CAD (group 3). Even though the calculated valve area was similar in all three study groups, group 1 patients had higher values for ejection fraction (65 +/- 9%, 51 +/- 17%, and 48 +/- 13%; p = 0.0002), systolic mass-to-volume ratio (9.2 +/- 3.9, 5.6 +/- 2.8, and 5.2 +/- 2.2; p = 0.0001), and cardiac index (2.9 +/- 0.7, 2.5 +/- 0.7, and 2.3 +/- 0.6 l/min.min2; p = 0.015) than patients in groups 2 and 3, respectively (mean +/- SD). Mean circumferential wall stress was inversely related to severity of CAD. Multivariate analysis showed that CAD is an independent predictor of ejection fraction and mass-to-volume ratio in this group of patients. Thus, in an elderly population with severe aortic stenosis, patients with both obstructive and nonobstructive CAD have an increased incidence of left ventricular enlargement and systolic dysfunction. PMID- 2242531 TI - Left ventricular regional wall stress in dilated cardiomyopathy. AB - Left ventriculography with simultaneous pressure micromanometry was performed in 11 normal control subjects and 17 patients with dilated cardiomyopathy (DCM). Left ventricular silhouettes in the right anterior oblique projection were divided into eight areas, and regional wall stress was computed by Janz's method in each area excluding the two most basal areas. Wall stress was higher in DCM patients than in control subjects (p less than 0.01). The percent area changes from end diastole to end systole in each area were lower in DCM patients than in control subjects (mean for six areas, 22 +/- 14% versus 54 +/- 9%, respectively, p less than 0.01), but the coefficient of variation for the percent area changes in the six areas of the left ventricle in DCM patients was greater than that in control subjects (32 +/- 17% versus 15 +/- 4%, respectively, p less than 0.01), indicating regional differences in hypokinesis. There was a significant negative correlation between end-systolic regional wall stress and percent area change (r = -0.60 to -0.86, p less than 0.05) in each area. Thus, excessive regional afterload may play an important role in causing regional hypokinesis in DCM. PMID- 2242532 TI - Body surface mapping of high-frequency components in the terminal portion during QRS complex for the prediction of ventricular tachycardia in patients with previous myocardial infarction. AB - To study the clinical significance of terminal QRS high-frequency components for the prediction of ventricular tachycardia, an 87-lead body surface signal averaged mapping was performed in 21 healthy subjects (control) and in 41 patients with previous myocardial infarction (anterior, 20; inferior, 21). Mapping data were analyzed and averaged (129.7 +/- 26.5 beats) for 160 seconds, and the signal-averaged beat was filtered with a bidirectional bandwidth (80-250 Hz) digital filter. J-point was determined from the 87-lead RMS voltage of nonfiltered QRS. For each lead, we calculated the sum of the absolute value of filtered QRS from 20 msec ahead of the J-point to the J-point (A-20). The body surface distribution of A-20 was expressed as A-20 map. The maxima in A-20 maps were mainly located on the upper sternal region in healthy subjects, on the left anterior chest in patients with previous anterior myocardial infarction, and on the central anterior chest in patients with previous inferior myocardial infarction. In the patients in both the group with anterior myocardial infarction and the group with inferior myocardial infarction, the value of maximum was significantly greater than in the subjects in the control group (0.181 +/- 0.086 and 0.138 +/- 0.048, respectively, vs. 0.075 +/- 0.031 mV.msec; p less than 0.01). In patients with myocardial infarction (n = 41), the value of maximum was significantly greater with ventricular tachycardia (n = 11) than without ventricular tachycardia (n = 30) (0.240 +/- 0.076 vs. 0.130 +/- 0.043 mV.msec; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242533 TI - Long-term results of catheter ablation of idiopathic right ventricular tachycardia. AB - Ten consecutive patients with recurrent episodes of symptomatic, idiopathic, sustained monomorphic ventricular tachycardia (VT) originating in the right ventricle underwent an attempt at catheter ablation of the ventricular tachycardia. There were seven women and three men, with a mean age of 39 +/- 14 years (+/- SD). None of the patients had any evidence of structural heart disease. The VT had a left bundle branch block configuration and an inferior axis in each patient, and the mean cycle length was 313 +/- 75 msec. Based on the methods of induction of the VT and the response of the VT to verapamil, the VT mechanism was presumed to be reentry in six patients, triggered activity in three patients, and catecholamine-sensitive automaticity in one patient. Sites for ablation were guided by pace mapping, and an appropriate target site was identified in the right ventricular outflow tract in each patient. From one to three shocks of 100-360 J (mean total, 336 +/- 195 J) were delivered from a defibrillator between the tip of the ablation catheter (cathode) and a patch electrode on the anterior chest (anode). An electrophysiology test 7-9 days after ablation demonstrated that VT was still inducible in only one patient, who was treated with amiodarone. One other patient had a recurrence of VT 3 weeks after ablation and was treated with verapamil. Eight of 10 patients were not treated with antiarrhythmic medications and have had no episodes of symptomatic VT during 15-68 months of follow-up (mean follow-up, 33 +/- 18 months). There were no acute or long-term complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242534 TI - Indium-111-monoclonal antimyosin antibody studies after the first year of heart transplantation. Identification of risk groups for developing rejection during long-term follow-up and clinical implications. AB - The long-term clinical course and results of biopsies in 21 patients studied with monoclonal antimyosin antibodies more than 12 months after heart transplantation according to the presence and degree of antimyosin-antibody uptake is described. Eighteen men and three women aged 20-52 years (39 +/- 9 years) were studied with antimyosin antibodies 12-40 months (mean, 22 +/- 9 months) after heart transplantation, and followed for a mean of 18 months (10-28 months). The number of biopsies performed during follow-up was 102. Results showed normal antimyosin antibody studies in nine patients and abnormal studies in 12 patients. Myocyte damage was identified in 18 of the 102 biopsies (17.6%), one in the normal antimyosin-antibody group of patients and 17 in those patients with myocardial antimyosin-antibody uptake. Patients who developed rejection comprised 11% and 67% of each respective group; the mean number of rejection episodes per patient was 0.11 +/- 0.33 and 1.41 +/- 1.41, respectively (p less than 0.01). A trend was noted by which higher heart-to-lung ratios were associated with greater probability of rejection. Conclusively, 1) antimyosin-antibody studies performed after more than 1 year after heart transplantation indicate the presence and level of rejection activity, 2) groups of patients at risk for developing rejection at biopsy during long-term follow-up may be detected by antimyosin antibody study, and 3) surveillance for rejection and the degree of immunosuppression should be tailored to meet individual patient needs. PMID- 2242535 TI - Regional wall motion abnormalities after prolonged exercise in the normal left ventricle. AB - To determine whether regional wall motion abnormalities exist or contribute to left ventricular dysfunction, we obtained two-dimensional echocardiograms in 12 athletes before (baseline), immediately after (race finish), and 1 day after (recovery) the Hawaii Ironman Triathlon (a 3.9-km swimming, 180.2-km bicycling, and 42.2-km running event). Left ventricular short-axis and apical four-chamber views were computer digitized and divided into six segments, and radial chord shortening and area ejection fraction were calculated. Global ejection fraction fell at race finish (51% versus 46%, p less than 0.05) but recovered by 1 day (54%, p less than 0.01 by repeated-measures analysis of variance). With the apical four-chamber view, midseptal and apical-septal motion were reduced at race finish but returned to baseline during recovery (midseptal radial chord shortening: 21%, 8%, 22%; apical-septal radial chord shortening: 27%, 12%, 25%; midseptal area ejection fraction: 39%, 30%, 40%; apical-septal area ejection fraction: 44% baseline, 33% race finish, 43% recovery; all p less than 0.01). In contrast, with the parasternal short-axis view, wall motion did not change at race finish but tended to be elevated during recovery and became significant for anteroseptal motion (radial chord shortening: 29%, 30%, 36%; area ejection fraction: 49% baseline, 51% race finish, 58% recovery; both p less than 0.05). Lateral wall motion was unchanged. In addition, an index of septal curvature was calculated using the ratio of the septal-lateral wall minor axis to the perpendicular anteroposterior minor axis. At all three data collections, this ratio remained close to 1.0 at end systole and end diastole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242536 TI - Effect of nontransmural necrosis on epicardial potential fields. Correlation with fiber direction. AB - The effect of nontransmural necrosis on epicardial potential distributions was studied in 13 dogs. In previous studies, left ventricular epicardial pacing generated epicardial potential maps at QRS onset with a negative central area and two positive areas that faced the portions of the wavefront propagating along fibers. Subsequently, the positive areas expanded in a counterclockwise direction by 90 degrees to 120 degrees. In those studies, the rotatory expansion of the positive areas was tentatively attributed to the spread of excitation through deep myocardial layers, where fiber direction rotated counterclockwise from epicardium to endocardium. To test this hypothesis, we tried to interrupt the counterclockwise expansion of the positive area by creating localized, nontransmural necrosis at various depths in the left ventricular wall by injection of formalin or application of laser energy. Epicardial potential maps were obtained from a grid of 12 x 15 electrodes on a 44 x 56-mm area. Epicardial pacing from selected sites generated epicardial maps in which some positive areas were missing compared with controls. The direction of the straight line joining the pacing site to the site of missing positivity correlated well with the average fiber direction in the necrotic mass (r = 0.82, p less than 0.01). Angle between epicardial fiber direction and the straight line described above correlated well with the average depth of the necrosis, expressed as percent of the wall thickness (r = 0.95, p less than 0.01). These data support the hypothesis that the counterclockwise expansion of the epicardial positivity occurring after epicardial pacing results from excitation spreading along deep fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242537 TI - Strength-duration and probability of success curves for defibrillation with biphasic waveforms. AB - Certain biphasic waveforms require less energy to defibrillate than do monophasic pulses of equal duration, although the mechanisms of this increased effectiveness remain unclear. This study used strength-duration and percent success curves for defibrillation with monophasic and biphasic truncated exponential waveforms to explore these mechanisms. In part 1, defibrillation thresholds were determined for both high- and low-tilt waveforms. The monophasic pulses tested ranged in duration from 1.0 to 20.0 msec, and the biphasic waveforms had first phases of either 3.5 or 7.0 msec and second phases ranging from 1.0 to 20.0 msec. In part 2, defibrillation percent success curves were constructed for 6.0 msec/6.0 msec biphasic waveforms with a constant phase-one amplitude and with phase-two amplitudes of approximately 21%, 62%, 94%, and 141% of phase one. This study shows that if the first phase of a biphasic waveform is held constant and the second phase is increased in either duration or amplitude, defibrillation efficacy first improves, then declines, and then again improves. For pulse durations of at least 14 msec, the second-phase defibrillation threshold voltage of a high-tilt biphasic waveform is higher than that of a monophasic pulse equal in duration to the biphasic second phase (p less than 0.05), indicating that the previously proposed hypothesis of stimulation by the second phase is not the sole mechanism of biphasic defibrillation. These facts indicate the importance of the degree of tilt for the defibrillation efficacy of biphasic waveforms and suggest at least two mechanisms exist for defibrillation with these waveforms, one that is more effective for smaller second phases and another that becomes more effective as the second phase is increased. PMID- 2242538 TI - Bleeding time prolongation with streptokinase and its reduction with 1-desamino-8 D-arginine vasopressin. AB - The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 microgram/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean +/- SEM value of 119 +/- 15 to 191 +/- 34 seconds in the control group and from 114 +/- 6 to 188 +/- 18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592 +/- 119 seconds in the control group and 810 +/- 114 seconds in the experimental group (p = NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302 +/- 29 seconds (p less than 0.01 versus streptokinase) compared with 572 +/- 79 seconds (p = NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n = 16), von Willebrand factor antigen concentration (n = 17), and von Willebrand factor multimer distribution (n = 14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio. PMID- 2242539 TI - Area-at-risk determination by technetium-99m-hexakis-2-methoxyisobutyl isonitrile in experimental reperfused myocardial infarction. AB - In a canine model of reperfused myocardial infarction, we tested the hypothesis that after reperfusion, technetium-99m-hexakis-2-methoxyisobutyl isonitrile (Tc MIBI) tomographic imaging still reflects occlusion blood flow when the tracer is injected before reperfusion. Nine anesthetized dogs underwent 2 hours of coronary occlusion followed by 3 hours of reperfusion ending by being killed. Reference coronary blood flow was determined by radioactive microspheres injected during occlusion and after reperfusion. Biopsies in normal and ischemic myocardium and single photon emission computed tomography were obtained during occlusion and after reperfusion. Circumferential profiles were applied to axial slices divided into 5-degree sectors. The sectors were divided into 3 groups selected on the occlusion acquisition (normal, mildly reduced, and severely reduced) and compared with the postreperfusion acquisition. Tissular Tc-MIBI kinetics was assessed both by Tc-MIBI time-activity curves of normal and ischemic tissue obtained by biopsy and by the relative gradient between normal, ischemic, and necrotic postmortem tissue samples. In biopsy samples, Tc-MIBI content remained unchanged during occlusion and after reperfusion in normal as well as in ischemic tissue (4,662 +/ 2,237 counts/min/mg vs. 4,599 +/- 1,577 counts/min/mg in normal tissue, NS; 941 +/- 903 counts/min/mg vs. 1,087 +/- 721 counts/min/mg in ischemic tissue, NS). In postmortem tissue samples, there was a good correlation between occlusion microsphere blood flow and Tc-MIBI activity (r = 0.91). In the necrotic samples, mean normalized Tc-MIBI activity (10 +/- 17%) was slightly higher than the normalized microsphere blood flow (3 +/- 3%, p less than 0.001) but markedly lower than the normalized microsphere reperfusion blood flow (63 +/- 31%, p less than 0.001). Comparing the single photon emission computed tomographic acquisitions before and after reperfusion, Tc-MIBI activity remained unchanged in normal as well as in mildly reduced or severely reduced segments. Thus, our data are consistent with the hypothesis that Tc-MIBI traces blood flow, does not redistribute significantly despite reperfusion, and can be used for imaging the area at risk. PMID- 2242541 TI - Significance of discordant ST alternans in ventricular fibrillation. AB - With the use of epicardial mapping, we investigated the electrical alternans of the ST segment during acute myocardial ischemia and studied the difference in ST alternans between dogs with resultant ventricular fibrillation and those without it. During the 7-minute occlusion of the left anterior descending coronary artery below its first diagonal branch, 60 epicardial unipolar electrograms were recorded simultaneously at 1-minute intervals by a computerized mapping system. ST alternans was found in the eight dogs we observed. The amplitude of ST alternans (difference in the ST segment elevation of two consecutive electrograms) was greater in dogs with ventricular fibrillation (n = 4) than in those without it (n = 4) (3.92 +/- 1.24 versus 0.58 +/- 0.49 mV, p less than 0.05). Three of the four dogs with ventricular fibrillation demonstrated discordant ST alternans (i.e., adjacent leads were out of phase). Results from the present study indicate that an increased amplitude and discordance of ST alternans during acute myocardial ischemia are related to ventricular fibrillation and act as indicators of time and spatial unevenness of ventricular repolarization. PMID- 2242540 TI - Effects of brief coronary occlusion and reperfusion on porcine coronary artery reactivity. AB - The loss of coronary vasodilator reserve after ischemia-reperfusion may be due to endothelial injury, and this vascular dysfunction may contribute to functional alterations observed after ischemia. To determine whether endothelial dysfunction occurs after relatively brief periods of moderate low-flow ischemia in vivo, open chest swine were subjected to 15 minutes of critical, subtotal left anterior descending coronary artery occlusion (80%) followed by 60 minutes of reperfusion. Serial measurements of regional coronary flow were made with the radiolabeled microsphere technique. After 60 minutes of reperfusion, the left anterior descending coronary artery was excised together with a section of the normally perfused left circumflex coronary artery to examine in vitro the relaxations to the endothelium-dependent dilators ADP and bradykinin and to the endothelial independent dilators sodium nitroprusside and adenosine. Contractions to serotonin in quiescent rings were also examined. Endocardial and transmural blood flows recovered to preocclusion levels within 60 minutes of reperfusion, as did the epicardial-to-endocardial ratio. Vascular responses in isolated, reperfused left anterior descending coronary artery rings were significantly different from responses in control left circumflex coronary artery rings. Endothelium-dependent relaxations to adenosine diphosphate and bradykinin were significantly depressed in the left anterior descending coronary artery rings compared with left circumflex coronary artery rings (p less than 0.05). Serotonin-induced contractions were significantly greater in occluded-reperfused left anterior descending than in left circumflex coronary arteries (p less than 0.05). Relaxations to adenosine and sodium nitroprusside were not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242542 TI - Wenckebach periodicity in single atrioventricular nodal cells from the rabbit heart. AB - Previous studies have suggested that Wenckebach periodicity in cardiac tissues may occur because of discontinuous propagation across junctional areas in which there is high intercellular resistivity or different cell types. Under these conditions, the impulse may stop altogether at a given junction, or may renew its propagation but only after a step delay imposed by the diastolic time-dependent recovery in the excitability of cells distal to that junction. Accordingly, Wenckebach periodicity in the atrioventricular node may be explained in terms of electrotonically mediated delay in the activation of the nodal cells. To test this hypothesis, we have studied recovery of excitability, and susceptibility to rate-dependent activation failure in single myocytes isolated from the adult rabbit atrioventricular node. Recordings were obtained by using the patch technique in the whole-cell, current clamp configuration. Repetitive stimulation of single atrioventricular nodal myocytes with depolarizing current pulses of critical amplitude yielded frequency-dependent stimulus response patterns that ranged from 1:1, through various Wenckebachlike periodicities (e.g., 5:4 and 4:3) to 2:1 and 3:1. Both typical and atypical Wenckebach structures were demonstrated, as well as "complex" patterns (e.g., reverse Wenckebach or alternating Wenckebach) previously ascribed to multiple levels of block. The diastolic recovery of excitability curve, determined by application of repetitive stimuli at cycle lengths that were longer than the action potential duration, showed a monotonic function with a refractory period outlasting the action potential duration (i.e., postrepolarization refractoriness). Abbreviation of the stimulation cycle length to values below those of the action potential duration revealed the existence of a period of supernormal excitability during the repolarizing phase of the action potential. In either case, the stimulus response patterns obtained were a direct consequence of the shape of the recovery of excitability curve. The monotonic portion of the recovery curve was fitted to an empirical equation that when iterated reproduced the stimulus response patterns observed in the atrioventricular nodal cell. Our data demonstrate that recovery of excitability after an action potential is indeed a function of the diastolic interval, and that this slow process sets the conditions for the development of Wenckebach periodicity in the atrioventricular node. PMID- 2242543 TI - Increased endothelin in experimental heart failure. AB - Recent studies demonstrate that endothelin, a potent endogenous vasoconstrictor peptide, circulates in plasma of normal animals and humans. However, the role of this peptide in pathophysiological states remains unclear. The present study was designed to test the hypothesis that circulating endothelin concentrations are increased in experimental congestive heart failure (CHF), a pathophysiological state characterized by activation of vasoconstrictor mechanisms. In anesthetized dogs with CHF produced by 8 days of rapid ventricular pacing (n = 28), circulating plasma endothelin was increased compared with values for normal controls (n = 28; 20.4 +/- 1.4 versus 9.7 +/- 0.9 pg/ml, respectively; p less than 0.0001). A plasma endothelin level of more than 14.0 was a sensitive and specific indicator of significant CHF. Moreover, within the group with experimental CHF, right atrial pressure and pulmonary capillary wedge pressure correlated independently with circulating endothelin levels. Based on recent studies demonstrating the physiological actions of twofold increases in circulating endothelin, as observed in the present study, a possible role for endothelin in the pathophysiology of CHF is advanced. PMID- 2242544 TI - Coronary artery revascularization. Critical need for, and consequences of, objective angiographic assessment of lesion severity. PMID- 2242545 TI - Channel specificity in antiarrhythmic drug action. Mechanism of potassium channel block and its role in suppressing and aggravating cardiac arrhythmias. AB - Although work on class III antiarrhythmics remains at an early stage, these agents still appear to possess greater efficacy and less proarrhythmia than conventional class I agents in those experimental arrhythmia models considered to be most representative of the clinical situation. Although prolongation of repolarization carries with its own tendency for pause-dependent arrhythmogenesis (i.e., torsade de pointes), available data suggest that this may be a function of nonspecificity in potassium channel block rather than a general characteristic of class III activity. The availability of new and more selective blockers of specific cardiac potassium channels under development as class III agents have already helped to clarify basic questions about the ionic mechanism of repolarization in the heart, and one hopes that a growing clinical data base will eventually determine the relative safety and efficacy of these agents in preventing symptomatic and life-threatening arrhythmias. PMID- 2242546 TI - Balloon angioplasty for acute myocardial infarction. Was it buried alive? PMID- 2242547 TI - Peripheral arterial disease and subsequent cardiovascular mortality. A strong and consistent association. PMID- 2242548 TI - Calcium channel blockers and progression of coronary artery disease. PMID- 2242549 TI - Calcium channel blockers in chronic heart failure. The risks of "physiologically rational" therapy. PMID- 2242550 TI - Medical therapy of chronic stable angina pectoris. PMID- 2242551 TI - Flow in the descending aorta. A turn of the screw or a sideways glance? PMID- 2242552 TI - Catheter ablation of idiopathic right ventricular tachycardia. PMID- 2242553 TI - Electrophysiological testing in high-risk patients with previous myocardial infarction. PMID- 2242554 TI - Ticlopidine in unstable angina. PMID- 2242555 TI - 99mTc-MIBI and 201Tl as perfusion indicators. PMID- 2242556 TI - The academic life of a noninvasive test. PMID- 2242557 TI - Exercise standards. A statement for health professionals from the American Heart Association. PMID- 2242558 TI - ACC/AHA guidelines for the clinical application of echocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee to Develop Guidelines for the Clinical Application of Echocardiography). PMID- 2242559 TI - Assessment of fetal lung maturity: in search of the Holy Grail. PMID- 2242560 TI - Lead poisoning mechanisms. PMID- 2242561 TI - Improved phenotyping of apolipoprotein E: application to population frequency distribution. AB - A simple procedure for phenotyping apolipoprotein (apo) E directly from plasma has been developed for use in the lipid clinic laboratory. In this new method, 10 microL of serum or plasma is pretreated with neuraminidase (EC 3.2.1.18), which removes the sialic acid residues from apo E and eliminates additional bands, thereby ensuring correct phenotype assignment. After a rapid delipidation step, the samples are focused in vertical polyacrylamide mini-slab gels and immunoblotted with a polyclonal goat anti-apo E antibody, followed by a Protein G peroxidase conjugate. The accuracy of this method was confirmed by comparison with the established procedure of phenotyping by isoelectric focusing of delipidated very-low-density lipoprotein. In addition, sera from 203 subjects from Vancouver, selected without conscious bias, were used to determine the local distribution of the apo E alleles. We estimate that the relative frequencies of apo E alleles epsilon 2, epsilon 3, and epsilon 4 in this population are 0.086, 0.761, and 0.153, respectively. The speed and convenience of using minigels make this procedure ideal for clinical laboratory applications and large population studies. PMID- 2242562 TI - Isolation and structural identification of 9hydroxy-9desmethyl-cyclosporine. AB - A metabolite of cyclosporine has been isolated and its structure identified through use of HPLC and tandem mass spectroscopy. Fast atom bombardment mass spectrometry of an HPLC fraction co-eluting with 1 eta hydroxy-cyclosporine (M17) indicated that the mass of this metabolite was 2 Da greater than that of cyclosporine. Further isolation by HPLC yielded a pure fraction, which we analyzed with tandem mass spectrometry. Linear acyl fragment ions originating from the metabolite under collision-induced dissociation were consistent with the difference in mass being associated with amino acid 9 in the cyclosporine backbone. We propose a nomenclature system for future discussion of cyclosporine metabolites. PMID- 2242563 TI - "VRA-GlcNAc": novel substrate for N-acetyl-beta-D-glucosaminidase applied to assay of this enzyme in urine. AB - We describe a new chromogenic substrate and assay for determining N-acetyl-beta-D glucosaminidase (EC 3.2.1.30; NAG) activity in normal and pathological human urine. The novel substrate, ammonium 5-[4-(2-acetamido-2-deoxy-beta-D glucopyranosyloxy)-3- methoxyphenylmethylene]-2-thioxothiazolidin-4-one-3-ethan oate (VRA-GlcNAc), is prepared by condensation of vanillyl N-acetyl-beta-D glucosaminide and rhodanine-3-ethanoic acid. The phenol released by enzyme action has an intense absorption peak at 492 nm (epsilon = 37,000 L.mol-1.cm-1). The Km for NAG in urine was 0.5 mmol/L at pH 4.5. The substrate solution may be stored at 4-7 degrees C for one week without any increase in the substrate blank. For optimal assay conditions, we used a substrate concentration of 3 mmol/L and a 15 fold sample dilution at pH 4.5-5.0, with measurement at 505 nm, not significantly different from that at 492 nm. The sensitivity of the assay with VRA-GlcNAc as substrate is twice that of the MNP-GlcNAc [2-methoxy-4-(2'-nitrovinyl)-phenyl GlcNAc] procedure (Clin Chim Acta 1982;124:195-204) and can detect low amounts of minor NAG isoenzymes. This assay is an improvement on previously available colorimetric methods and could be easily incorporated into kits based on either an enzyme calibrant or the molar absorptivity of the phenol. PMID- 2242564 TI - Study of lipoprotein particles LpAI and LpAI:AII in patients before coronary bypass surgery. AB - Lipids, apolipoproteins, and LpAI and LpAI:AII particles were studied in 43 men (mean age 51, SD 7, years) 24 h before their coronary bypass surgery and in 54 control men (mean age 46 SD 9, years). LpAI and LpAI:AII were analyzed by electroimmunodiffusion and by a noncompetitive enzyme-linked immunoassay, respectively. Concentrations of LpAI and LpAI:AII in the bypass patients were significantly lower (P less than 0.001) than those in the controls. Apolipoprotein AI was significantly correlated with LpAI (P less than 0.001) and LpAI:AII (P less than 0.01) in controls, but only with LpAI:AII (P less than 0.001) in bypass patients. Discriminant analysis between controls and patients showed apolipoprotein AI to be the most powerful discriminant factor; the addition of LpAI and LpAI:AII did not improve discriminant power. We conclude that the determination of LpAI and LpAI:AII particles reflects metabolic disorders in patients but does not significantly influence the discrimination of such patients into risk groups. PMID- 2242565 TI - Quantitative and functional assays compared for determination of zymogen and activated human protein C. AB - We evaluated quantitative and functional assays for protein C, using either purified protein C samples or pooled normal plasma as assay standards. The purified protein C samples were examined as the zymogen form and after activation by thrombin. Mass concentrations of protein C were determined by amino acid analysis and confirmed by enzyme-linked immunosorbent assay (ELISA). Functional activity was assessed in both standard clot inhibition and amidolytic assays. The accuracy and precision of the ELISA was acceptable, with all three preparations of protein C having similar linear curves. The clot inhibition assay demonstrated marked variability when used according to the manufacturer's instructions; however, modifications to the protocol significantly decreased the CV, to less than 10%. Both activated protein C and the zymogen gave linear standard curves. Pooled normal human plasma gave a nonlinear curve, which contributed to inaccurate sample recoveries. We obtained the most nearly accurate recoveries when we used activated protein C as the assay standard. Amidolytic assays provided no insights into the appropriateness of the preparations for that assay format. A uniform, consistent source of protein C, e.g., recombinant activated protein C, would be useful for standardizing all assays of protein C. PMID- 2242566 TI - Flexibility of noncompetitive avidin-biotin immunoassay: immunoassay of lutropin applied to different signal detection systems. AB - I adapted the noncompetitive avidin-biotin immunoassay (NABA) of lutropin (LH) for use with radiometric, fluorometric, time-resolved fluorometric, and luminometric detection systems by changing the enzyme substrate or conjugating avidin with different labels. The corresponding methods were used to determine LH in 40 urine samples, and the results were compared with those obtained by an immunoenzymometric assay (IEMA), also based on the NABA principle. Scatter plots of the results showed a linear relation with high correlation coefficients (r = 0.972-0.983), and bias plots showed good agreement between the four comparison methods and the IEMA. The results indicate that the effectiveness of the NABA of LH is independent of the signal detection system. This means good flexibility for the user in choice of instrument and signal detection system. PMID- 2242567 TI - Gradient centrifugation to isolate platelets for determination of trace elements by neutron-activation analysis. AB - A nonionic iodinated compound, Nycodenz, was used for density-gradient isolation of platelets before analysis for trace elements by instrumental neutron activation. The platelet samples were almost free from plasma and erythrocytes, and the trace element contribution from additives was insignificant for the elements investigated. The reproducibility of the trace element analysis in platelets attests to the usefulness of density-gradient separation. Platelet samples were obtained twice, three weeks apart, from 10 healthy young women (ages 24 +/- 2 years). The mean (SD) concentrations were as follows: Se, 0.62 (0.16) mg/L and 4.7 (1.4) ng/10(9) platelets; Zn, 44 (10) mg/L and 333 (80) ng/10(9) platelets; Rb, 3.0 (0.5) mg/L and 23 (5) ng/10(9) platelets; and Cs, 24 (5) micrograms/L and 0.18 (0.04) ng/10(9) platelets. PMID- 2242568 TI - Evaluation of dialysis treatment in uremic patients by gel filtration of serum. AB - A group of substances of molecular masses between 300 and 1500 Da have been found to be toxic metabolites in patients with uremia. We determined the concentration in serum of these molecules in the following groups of patients: two hemodialyzed groups (one with cuprophane and the other with polyacrylonitrile dialyzers), one group treated with continuous ambulatory peritoneal dialysis, one group of nondialyzed azotemic patients, and one control group of healthy persons. Ultrafiltrates of the subjects' sera were fractionated on Sephadex G-15 followed by ion-exchange chromatography. Eluates were monitored by absorbance at 254 and 206 nm. Partially characterized peaks P1 and P2, obtained by gel filtration, correlated with the concentration of creatinine in serum; their concentrations were significantly (P less than 0.01) larger in hemodialyzed groups than in peritoneal dialyzed or in nondialyzed azotemic patients. After ion-exchange chromatography, two peaks (P'5 and P'6) correlated with serum creatinine and also were larger in hemodialyzed patients than in the other groups. Apparently, adequate discrimination is obtained by gel-filtration analysis and further analysis by ion-exchange chromatography does not provide additional information in most of the affected patients. PMID- 2242569 TI - Impact of protein measurements on standardization of assays of apolipoproteins A I and B1. AB - In 1989 the Committee on Apolipoproteins of the International Federation of Clinical Chemistry and the Centers for Disease Control conducted an international survey of total-protein measurements of isolated low-density lipoproteins (LDL) and delipidated high-density lipoproteins (HDL), and of their relationships to the National Institute of Standards and Technology (NIST) bovine serum albumin (BSA) Standard Reference Material (SRM). Most of the 93 apolipoprotein laboratories surveyed use the Lowry total-protein method. Results reported with the LDL preparations demonstrated a large bias and variation among methods; those with delipidated HDL were not as great, but were similar to those for BSA. Performance improved appreciably with use of the Lowry-sodium dodecyl sulfate method and the NIST BSA SRM for protein measurement. The total CVs, including among-laboratory and within-laboratory errors, averaged approximately 50% and 23% for LDL, 17% and 11% for HDL, and 18% and 11% for BSA solutions by all methods and by the Lowry methods, respectively. Regardless of the methods used, greater variability of the protein measurements was seen with the normally occurring LDL than with the nonlipoprotein BSA or delipidated HDL. The mean CV values for all samples among laboratories averaged between 10% and 15% with the modified Lowry methods; the biuret method gave the highest among-laboratory CV, 34%; the Kjeldahl had the lowest, 7.7%. Use of the same methodology and primary nonapolipoprotein standard is essential for comparability of protein results for apolipoprotein primary standard solutions. This is especially true for apolipoprotein B, because its inherent properties and lability make protein analysis difficult. This study supports the use of a standardized selected Lowry sodium dodecyl sulfate method traceable to quantitative amino acid analysis as a point of reference for determining the protein concentration of primary calibration reference materials for apolipoproteins. PMID- 2242570 TI - Diet-related reference values for plasma amino acids in newborns measured by reversed-phase HPLC. AB - We have measured by reversed-phase HPLC concentrations of amino acids in plasma in groups of 80 normal appropriate-weight term babies fed from birth either a casein formula (WhiteCap SMA, n = 26), a whey formula (Gold Cap SMA, n = 26), or breast milk (n = 28). They were studied from day 11 to week 15 postpartum. The trend was towards an increase in amino acid concentrations in plasma with age, more marked in formula-fed than in breast-fed infants. Reference values were derived for each group. Both formula-fed groups showed several differences from the breast-fed group. Detailed examination indicated that tyrosine, phenylalanine, and methionine concentrations were increased in the casein-fed group greater than 20% of the time, but only threonine was similarly increased in the whey-fed group. Other amino acids, different ones for each formula group, were increased less frequently. There were no consistent correlations with any aspect of infant growth. Appropriate reference values are important for interpreting amino acid concentrations in plasma from newborns and for evaluating the effects of any future dietary modifications to infant formulas. HPLC analysis provides a suitable highly sensitive method for undertaking such studies. PMID- 2242572 TI - Particulate (high-molecular-mass) and soluble alkaline phosphatase in urine determined by high-performance liquid chromatography. AB - We detected in urine by HPLC two enzyme fractions of alkaline phosphatase (AP, EC 3.1.3.1), soluble and particulate, analogous to those in serum. The second fraction was eluted with high-salt-content eluent at the same elution time as high-molecular-mass, or particulate, AP in serum. AP characterization in urine from a patient with acute rejection crisis showed a greater sensitivity of the particulate form to treatment with L-phenylalanine, which suggests a higher content of intestinal-type AP in the particulate form. The soluble fraction showed a more liver-type AP behavior. Changes in the chromatograms after the sample was treated with 1-butanol and Triton X-100 support a membrane origin of the particulate AP. Urinalyses from patients with acute renal disease showed increased activity of soluble and particulate AP, with a relatively greater increase of particulate AP. PMID- 2242571 TI - Ultrasensitive two-site immunometric assay of human lutropin by time-resolved fluorometry. AB - A rapid, sensitive two-site immunometric assay for human lutropin (LH), with two monoclonal antibodies directed against the beta subunit, has been developed with time-resolved fluorescence as the detection principle. The cross-reactivities with human thyrotropin and human follitropin are negligible and that with human choriogonadotropin is 1% in the standard two-step protocol. Free beta subunits of LH are also detected. Besides the standard procedure (45 + 15 min), more rapid alternative protocols (15 + 15 min or 30 min in one step) have also been evaluated. The minimum detectable dose per well is approximately 1 amol (10(-18) mol), corresponding to less than 0.01 int. unit/L, for a sample volume of 25 microL and less than 0.001 int. unit/L for 200-microL samples. The intra- and interassay CV is less than 6% for LH concentrations from 0.2 to 250 int. units/L. With 200-microL sample volumes, intra-assay variation is less than 6% at 0.04 int. unit/L and interassay variation is 7% at 0.05 int. unit/L. The very high sensitivity and reproducibility of the presented method enables assay of low prepubertal and of suppressed LH concentrations, and represents a clear improvement over currently available immunoassays. PMID- 2242573 TI - Enzymatic method for selective determination of 4-aminobenzoic acid in urine. AB - We developed a method for the selective determination of 4-aminobenzoic acid by use of 4-aminobenzoate hydroxylase (EC 1.14.13.27) to convert 4-aminobenzoic acid to 4-hydroxyaniline. The subsequent conversion of 4-hydroxyaniline to indophenol dye was quantified colorimetrically. The method is reproducible, and the assay response is linear up to 40 mumol/L. Selectivity exceeding that of the current colorimetric assays was demonstrated for these enzymatic determinations of 4 aminobenzoic acid concentrations in urine samples from patients undergoing tests of pancreatic function with bentiromide. This method effectively minimizes interferences from drugs and diet, a problem in current colorimetric methods. PMID- 2242574 TI - Idiometric assay: noncompetitive immunoassay for small molecules typified by the measurement of estradiol in serum. AB - We report here a novel noncompetitive immunoassay applicable to the measurement of small-molecular-mass compounds and typified by the direct measurement of estradiol in serum. Two types of anti-idiotypic antibody recognize different epitopes within the hypervariable region of the specific primary antibody (e.g., anti-estradiol). The first anti-idiotype (betatype) recognizes an epitope at the unoccupied binding site, which is masked in the presence of the analyte (e.g., estradiol). The second (alphatype) recognizes an epitope close to the binding site and is unaffected by the presence or absence of the analyte, but is sterically hindered from binding to the primary antibody in the presence of the betatype. The use of these matched antibodies (primary antibody, alphatype, and betatype) has enabled the development of a method for determining antibody occupancy that is not based on a conventional two-site assay. An excess amount of purified monoclonal antibody against estradiol is immobilized onto the walls of microtiter wells. After the capture of analyte, the unoccupied antibody sites are blocked by the addition of an excess amount of betatype. Subsequently, analyte occupancy is determined by the addition of excess europium-labeled alphatype, incubation, washing, and time-resolved fluorometry. The method demonstrates good sensitivity, precision, and comparability with alternative competitive immunoassays. PMID- 2242575 TI - Candidate reference method for determining creatinine in serum: method development and interlaboratory validation. AB - We describe a "high-performance" liquid chromatographic (HPLC) method for accurately determining creatinine in serum. After prechromatographic precipitation of protein, we performed isocratic ion-exchange chromatography with ultraviolet detection (234 nm). Analytical results showed linearity up to 1770 mumol/L, a detection limit of 22 mumol/L, an average analytical recovery of 101%, and a CV ranging from 3% to 11%. We used certified human serum (National Institute of Standards and Technology), and additional lyophilized serum pools also assayed by definitive isotope-dilution mass spectrometry, to validate the accuracy of the HPLC method. In addition, the isocratic HPLC results showed close agreement with those obtained with a step-gradient HPLC method. We also compared the isocratic HPLC method with alkaline picrate and enzymatic methods. Our findings with samples from nonuremic, uremic, and diabetic ketoacidotic patients confirmed the positive bias previously reported with the alkaline picrate method. Interlaboratory transferability of the method was demonstrated with various commercial instruments and analytical columns. We evaluated column stability and possible interference from endogenous or exogenous compounds. On the basis of our analytical findings, we recommend the isocratic HPLC method as a candidate Reference Method for determining creatinine in serum. PMID- 2242576 TI - Analysis of 8-methoxypsoralen by high-performance liquid chromatography. AB - We report a simple and rapid procedure for assaying 8-methoxypsoralen (8-MOP) in plasma by high-performance liquid chromatography (HPLC). The standard curve for the assay is linear for 8-MOP from 15 to 500 micrograms/L (y = 0.002x-0.01, r = 0.99) with a lower limit of detection of 1.5 micrograms/L. Intra-assay precision (CV) was 6.0% at the 100 micrograms/L concentration and 10.0% at 50 micrograms/L (n = 30 each). Interassay precision was 6.4% at 100 micrograms/L and 7.0% at 50 micrograms/L (n = 50 each). Extraction recovery of 8-MOP was 98%. Common antiarrhythmics, sedatives, and hypnotics were found not to interfere. PMID- 2242577 TI - Simple screening tests for the emergency identification of methanol and ethylene glycol in poisoned patients. AB - We have developed simple and rapid screening tests for methanol and ethylene glycol in plasma of poisoned patients, based on the Toxi-Lab alcohol screening test. The compounds are first converted to formaldehyde, which diffuses from the patient's sample into a glass-fiber test sheet impregnated with Schiff's formaldehyde detection reagent. Subsequent exposure of the test sheet to acid and heat distinguishes formaldehyde from acetaldehyde. We recommend that samples giving positive results be analyzed by another technique to confirm the identity and concentration of the poison for use in prognosis and treatment. PMID- 2242578 TI - Double monoclonal time-resolved immunofluorometric assay of beta 2-microglobulin in serum. AB - Previously reported immunochemical assays of beta 2-microglobulin (beta 2m) have usually been based on polyclonal antisera. We have developed a "sandwich"-type time-resolved immunofluorometric assay (TR-IFMA) for beta 2m in serum, based on two monoclonal antibodies against human beta 2m. Microtiter wells are coated with the capture antibody, and the tracer antibody is labeled with a europium chelate. In a simple and fast assay procedure, prediluted serum samples are incubated with the tracer for 1 h in the microtiter wells, after which the wells are washed and the fluorescence of Eu is measured. The mean analytical recovery was 101.8% and results by TR-IFMA showed a good linear correlation with those by an established radioimmunoassay. The analytical range of TR-IFMA is large and well suited for clinical purposes. PMID- 2242579 TI - Enzyme immunoassay for measuring antibodies against skeletal muscle in patients with myasthenia gravis. AB - We developed a highly sensitive enzyme immunoassay (EIA) for measuring IgG and IgM antibodies against human skeletal muscle (SM) component and tested sera from 100 patients with myasthenia gravis (MG), 59 with thymoma and 41 without thymoma. We found that the frequency of anti-SM IgG antibodies was significantly higher in MG patients with (81%) than without (37%) thymoma. The titers of the anti-SM IgG antibodies measured by EIA correlated well with those measured by RIA (r = 0.81, P less than 0.01). We also found that 12% of the myasthenic patients with thymoma and 15% without it had anti-SM IgM antibodies. There was no correlation between the titers of the IgG and IgM antibodies. Our EIA provides a measure of anti-SM antibodies that is of comparable sensitivity to that of RIA. PMID- 2242580 TI - Abbott TDx monoclonal antibody assay evaluated for measuring cyclosporine in whole blood. AB - We report here the evaluation of the Abbott TDx assay with a monoclonal antibody for selectively quantifying cyclosporine (CsA) in whole blood. Over the clinically relevant concentration ranges, results with this assay demonstrated within- and between-run CVs of less than 2.5% and 5%, respectively; sensitivity of 25 micrograms/L; good analytical recovery (100.3%); and linearity with whole blood specimens. The percentage cross-reactivity of the major CsA metabolites varied from 15.3% for AM9 (M-1), 8.2% for AM1 (M-17), and 3.7% for AM4N (M-21), to less than 3% for the other metabolites tested. Results with the TDx assay (y) correlated well with those by the Sandimmune selective RIA (x; Sandoz) with blood specimens from 44 renal-transplant recipients (n = 44, x= 187.3, y = 198.9, y = 5.49 + 1.03x, r = 0.987). The TDx values were on average 24% higher than those by HPLC (x') with the same patients' specimens (n = 44, x' = 159.9, y = 198.9, y = 15.9 + 1.14x', r = 0.967). We conclude that the Abbott TDx monoclonal antibody assay provides a rapid, precise, and accurate means for quantifying CsA in whole blood. PMID- 2242581 TI - Evaluation of the PG-Numeric assay for semi-automated analysis for phosphatidylglycerol in amniotic fluid. AB - We evaluated the performance of the PG-Numeric (PGN; Isolab, Inc.) enzymatic assay for phosphatidylglycerol (PG) adapted for semi-automated analysis on the Cobas-Bio (Roche) centrifugal analyzer. We evaluated precision, linearity, and potential interference from endogenous glycerol. In addition, we compared the results of the PGN assay with those for two other PG assays. Amniostat-FLM (AFLM; Hana Biologics) and phosphatidylglycerol/sphingomyelin ratio (PG/S), on amniotic fluid samples from 51 patients. Within-run and total CVs for the PGN test (n = 80) were respectively 8.6% and 11.4% for PG at 2.6 mumol/L, and 4.5% and 6.2% at 7.3 mumol/L. The PGN test exhibited no significant deviation from linearity between PG concentrations of 0.4 and 15 mumol/L. Endogenous glycerol up to 500 mumol/L did not affect PGN results significantly. Results of the PGN assay compared favorably with those of the other PG assays for tests of fetal lung maturation. The Cobas-Bio adaptation of the PGN test performed well analytically and clinically, and allowed the determination of PG in less than 1 h. PMID- 2242582 TI - Simultaneous measurement of two major prostacyclin metabolites in urine. AB - We describe a combined HPLC-RIA technique to measure both major metabolites of prostacyclin (PGI2): 6-keto PGF1 alpha and 2,3-dinor-6 keto PGF1 alpha. The measurement of the former, which originates from renal blood vessels, and the latter, from systemic vessels and the liver, may provide a better overall evaluation of production than measurement of one metabolite. An aliquot of acidified urine with added 3H-labeled metabolites is adsorbed and then eluted from a C18 Bond-Elut column. The sample is then passed through an HPLC system by use of an isocratic solvent combination that separates the two metabolites from known prostaglandins. The purified metabolites are then quantified by RIA. Using a logit-log10 transform, one can measure between 12 and 250 pg of either metabolite, with high accuracy and precision (CVs of 12% for a low concentration and 7% for a high concentration). Reference values for apparently healthy subjects were, respectively, 107 (SD 45) and 171 (SD 69) ng/g creatinine for 6 keto PGF1 alpha and the dinor metabolite in men (n = 18) and 45 (SD 22) and 141 (SD 28) ng/g creatinine, respectively, in women (n = 15). Indomethacin in standard doses reduced both metabolite values by 50%. Intravenous administration of angiotensin II (5 ng/kg of body wt per minute) did not alter excretion rates, but equipressor doses of norepinephrine (0.1 microgram/kg per minute) increased the production of both metabolites (6-keto greater than dinor). PMID- 2242583 TI - Effect of occupational lead exposure on lymphocyte enzymes involved in heme biosynthesis. AB - Lead exposure is a well-known cause of increases in urinary coproporphyrin and erythrocyte zinc-protoporphyrin, so these compounds are often used to monitor occupational lead exposure. The increased concentrations are usually assumed to result from lead inhibition of two of the mitochondrial enzymes of heme biosynthesis, coproporphyrinogen oxidase (EC 1.3.3.3) and ferrochelatase (EC 4.99.1.1). We studied 88 subjects in whom the degree of occupational lead exposure was established by measuring erythrocyte lead and protoporphyrin. Assay of lymphocyte coproporphyrinogen oxidase and ferrochelatase activities showed that these enzymes were unaffected by lead exposure, as was a related enzyme, lymphocyte NADH-ferricyanide reductase. We propose alternative explanations for the increased concentrations of coproporphyrin and zinc-protoporphyrin seen in lead exposure. PMID- 2242584 TI - Development and evaluation of a simplified dot-blot method for detecting the delta F508 mutation in cystic fibrosis. AB - The recent discovery of the cystic fibrosis gene enables DNA-based testing for the direct identification of the deletion of three basepairs coding for phenyalanine at codon 508, the major mutation responsible for the disease. This mutation can be detected by analysis of amplified DNA with allele-specific oligonucleotide probes. We have simplified the procedure of Kerem et al. (Science 1989;245:1073-80) so that the assay can be routinely completed in one working day, starting with an extracted DNA sample. Addition of salmon-sperm DNA to the product of the polymerase chain reaction greatly improved the quality of the hybridization signal. The precision of the method was evaluated by blind analysis and interpretation of results for 100 specimens from 25 patients. The same result was obtained for each patient analyzed separately four times, and four independent observers agreed on the interpretation of results for all 100 specimens. No specimen required repeat analysis to produce interpretable results. We conclude that this method is reliable and convenient for routine clinical laboratory use. PMID- 2242585 TI - Determination of beta-carotene and its cis isomers in serum. AB - All-trans-beta-carotene was resolved from its cis isomers in human serum by reversed-phase "high-performance" liquid chromatography. Absorption spectra of the cis peak suggested that 13-cis-beta-carotene was the predominant cis isomer. Analyses and recovery studies of fresh and stored sera eliminated the possibility that isomerization had occurred in samples during handling or storage. The average analytical recovery was 101.9% for standards of the all-trans-, 9-cis-, and 13-cis-beta-carotene compounds in pooled serum samples. We also demonstrated that cis isomers had not formed after the blood was drawn and that cis isomers of beta-carotene are present at significant concentrations in the human circulation. PMID- 2242586 TI - Determination of magnesium in serum by the technicon SMAC with a calmagite method with blank correction. PMID- 2242587 TI - Long-term in vitro stability of cyclosporine in whole-blood samples. PMID- 2242588 TI - Markedly increased concentrations of ferritin in an AIDS patient with disseminated histoplasmosis. PMID- 2242589 TI - Unbound and transthyretin-bound retinol-binding protein in serum and urine from diabetic patients with nephropathy and proteinuria. PMID- 2242590 TI - Three-minute whole-blood cholesterol screening test evaluated. PMID- 2242591 TI - Enzymatic reagents for quantifying total plasma cholesterol from dogs, rats, and hamsters. PMID- 2242592 TI - Hyponatremia is not a regulator of serum thyroxin. PMID- 2242593 TI - Macro creatine kinase in a case of carnitine palmitoyltransferase deficiency. AB - A stout man was admitted to the hospital with acute rhabdomyolysis associated with macro creatine kinase (macro-CK, EC 2.7.3.2). This anomaly of CK was detected by gel electrophoresis as an atypical band between CK-MB and CK-MM, classified according to Stein's criteria (Clin Chem 1982; 28:19-24) as type 1, and identified by immunofixation electrophoresis as containing CK isoenzymes MM and MB and immunoglobulin A. Muscle biopsy showed that the etiology of rhabdomyolysis in this case was deficiency of carnitine palmitoyltransferase (CPT, EC 2.3.1.21) in the muscle. We report the first observation of macro-CK in a case of CPT deficiency; its presence may result from recurrent rhabdomyolytic attacks owing to CPT deficiency, and may suggest underlying enzymic abnormality in muscle. PMID- 2242594 TI - Atypical enolase isoenzyme in serum: a macroenolase formed from the alpha gamma hybrid form. AB - We report an abnormal pattern for enolase (EC 4.2.1.11) isoenzymes in the serum of a patient with squamous cell lung carcinoma. The alpha alpha-isoenzyme was present but the alpha gamma form was not detected, and near the point of application on the electrophoretogram was an abnormal band. We determined that the abnormal fraction corresponded to a macroenolase, composed of the alpha gamma isoenzyme complexed with IgG. From a practical point of view, the presence of such a macroenolase, containing gamma-subunits, results in falsely increased results for neuron-specific enolase (NSE) in procedures that determine only the NSE concentration without consideration of the enolase isoenzymes. PMID- 2242595 TI - Excess serum osmolality gap after ingestion of methanol. AB - Two cases of methanol ingestion and one case of combined methanol and ethylene glycol ingestion are presented to illustrate the large differences that exist between the serum osmolality gap and the measured methanol (plus ethylene glycol) concentration(s) before treatment of these poisonings. After treatment with intravenous ethanol and hemodialysis was initiated, the differences disappeared in all three cases. We speculate that one or more metabolites with osmotic activity are formed in cases of methanol intoxication where no ethanol has also been consumed. The possible identity of these compounds is discussed. PMID- 2242596 TI - Abnormal lactate dehydrogenase isoenzyme pattern in serum of a patient with a neuroendocrine tumor. PMID- 2242597 TI - Measurement of free choriogonadotropin beta-subunit in patients with testicular tumors. PMID- 2242598 TI - Advantages of initial population screen with determinations of total cholesterol in serum and of lipoproteins by electrophoresis. PMID- 2242599 TI - Fluoride affects Coomassie Brilliant Blue measurement of protein in cerebrospinal fluid. PMID- 2242600 TI - Glycerol-blanked triglyceride assays with laboratory animals. PMID- 2242601 TI - Concentrations of rare earth elements in plasma and urine of healthy subjects determined by inductively coupled plasma mass spectrometry. PMID- 2242602 TI - Variations in measured alkaline phosphatase activity: influence of isoenzymes and buffer systems. PMID- 2242603 TI - Strategies in antibody therapy of cancer. PMID- 2242604 TI - A novel strategy for targeting CD4+ PPD-reactive T cells against tumour cells using PPD monoclonal antibody heteroconjugates. AB - We have constructed PPD monoclonal antibody heteroconjugates specific for a tumour-associated antigen of C57BL/6 melanomas or for human complement component C3d fixed de novo to murine fibrosarcoma cells (MC6A). The ability of our heteroconjugates to target CD4+ PPD-reactive T cells against the appropriate tumour targets was then determined in vitro. Heteroconjugate-treated B16-F10 and MC6A tumour targets were both able to present PPD to the specific T cells, resulting in activation and concomitant lymphokine secretion. Secreted lymphokines were then demonstrated to cause significant tumour cytolysis and cytostasis in vitro. Preliminary experiments in vivo suggest that this targeting system may provide the basis for a future immunotherapeutic strategy. PMID- 2242605 TI - Autoantibodies to endothelial cells and neutrophil cytoplasmic antigens in systemic vasculitis. AB - The interaction of circulating autoantibodies with the endothelium may be an important mechanism in the pathogenesis of systemic vasculitis. In a prospective study, we looked for circulating antiendothelial cell autoantibodies (AECA) and anti-neutrophil cytoplasm autoantibodies (ANCA) in 80 patients with suspected systemic vasculitis. AECA were measured using an isotype-specific cellular ELISA incorporating human umbilical vein endothelial cells. ANCA activity was determined by indirect immunofluorescence and radioimmunoassay. Sequential studies were performed on sera from four cases with dual positivity, where autoantibody binding was compared with von Willebrand factor (vWF) concentration and disease activity. IgG AECA were significantly higher in the 27 ANCA-positive sera as compared with normal controls (P = 0.027) with IgG (P = 0.009) and IgA (P = 0.046) AECA isotypes correlating with ANCA positivity; in contrast, no differences were found between AECA levels in the ANCA-negative sera and the normal controls. Cross-inhibition studies pointed to the co-existence of two autoantibody populations. An association between autoantibody binding, disease activity and vWF concentration was found for both ANCA and AECA. Some patients with systemic vasculitis have detectable AECA that recognize different epitopes to ANCA and like ANCA, their titre correlates with disease activity and thus they may have a pathogenetic role in these conditions. PMID- 2242606 TI - Increased production of the third component of complement (C3) by monocytes from patients with systemic lupus erythematosus. AB - We measured in vitro C3 production by peripheral blood monocytes from patients with systemic lupus erythematosus (SLE), and found it to be significantly greater than that from normal controls. We also found that monocytes from SLE patients with active disease produced a markedly larger amount of C3 than those from SLE patients with inactive disease. Production of C3 by monocytes correlated with serum levels of anti-dsDNA antibodies and inversely correlated with serum C3 levels in SLE patients. Serial measurement of C3 in the culture supernatant from each SLE patient showed that C3 production by monocytes fell in parallel with a decrease of disease activity. The effect of corticosteroids was ruled out as there was no relation between the level of C3 production by monocytes and the dose of prednisolone. This seems to be the first study in which the C3 production was assayed at a cellular level in SLE patients, and this study suggests that the local C3 production is increased in SLE patients. PMID- 2242607 TI - Anti-heparan sulphate reactivity in sera from patients with systemic lupus erythematosus with renal or non-renal manifestations. AB - Previously, we have shown that anti-DNA can bind to heparan sulphate (HS), a constituent of the glomerular basement membrane (GBM). We hypothesized that binding of anti-DNA to HS in the GBM plays a role in the onset of systemic lupus erythematosus (SLE) nephritis. To test this hypothesis we measured the anti-HS reactivity in cross-sectional and longitudinal studies of SLE patients with or without nephritis. In the transverse serum study single serum samples from 26 SLE patients were studied. We found no correlation between anti-HS reactivity and previously development of nephritis (anti-HS positive: seven out of 16 with history of nephritis, two out of 10 without nephritis). However, six of the seven anti-HS positive sera in the nephritis group were obtained within 1 month of the onset of nephritis, suggesting a temporal relationship between anti-HS reactivity and onset of nephritis. In the longitudinal serum study between six and 16 serum samples were studied from each of 10 SLE-patients. In five out of five episodes of nephritis we found anti-HS reactivity before the onset or exacerbation of the nephritis. In four non-renal manifestations anti-HS reactivity was found in only one episode; in none of the three patients who remained clinically stable did serum samples show anti-HS reactivity. Anti-HS reactivity was only found in sera positive for anti-DNA by Farr assay but the anti-HS titre was not a mere reflection of the reactivity measured in the Farr assay. This indicates that only a subpopulation of anti-DNA can bind to HS. We found a high correlation (r = 0.99) between anti-HS reactivities in plasma and serum and we conclude that anti HS reactivity in serum samples from SLE patients is not due to in vitro complex formation during clotting. Although further prospective analysis is necessary, our data suggest that measurement of anti-HS reactivity in SLE patients might identify patients at risk for the development of nephritis. PMID- 2242608 TI - Thyroid autoantigens and human T cell responses. AB - We investigated the ability of T cells from patients with Hashimoto's thyroiditis and with Graves' disease as well as control donors to proliferate in response to thyroid peroxidase (TPO) and thyroglobulin using (i) lymphoid cells from different lymphoid organs; (ii) unfractionated or CD8- depleted lymphoid suspensions or T cells + autologous low density cells (LDC); (iii) 200 microliters well cultures and 20-microliters hanging-drop microcultures; and (iv) intact TPO and thyroglobulin, denatured thyroglobulin and 12 synthetic peptides predicted on the basis of the amino acid sequence of TPO to be T cell epitopes. In 200-microliters well cultures, proliferative responses (assessed in terms of 3H-thymidine uptake) to intact TPO or thyroglobulin, digested thyroglobulin or synthetic TPO peptides were not significantly different in unfractionated or CD8 depleted lymphoid suspensions from blood, thyroid or lymph nodes of TPO/thyroglobulin autoantibody-positive patients, autoantibody-negative patients or control donors. In contrast, blood T cells from some high titre patients with Hashimoto's thyroiditis (but not from healthy individuals) proliferated in response to intact thyroglobulin or TPO presented by autologous LDC in hanging drop microcultures. Heat denatured thyroglobulin (with which thyroglobulin autoantibodies do not interact) did not stimulate proliferation and this observation, together with the ability of T cells from some patients to respond to intact thyroglobulin in the absence of LDC, indicated that thyroglobulin specific B cells may be involved in antigen presentation. As we were unable to demonstrate proliferation by blood T cells + LDC from all thyroglobulin antibody positive patients with Hashimoto's thyroiditis, our studies suggest that the presence of sufficient precursor T cells, as well as the number and type of antigen-presenting cells, are critical for T cell proliferative responses to human TPO and thyroglobulin. PMID- 2242609 TI - Patients with myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin. AB - Patients with myasthenia gravis (MG) and thymoma have in their sera antibodies which react with non-receptor antigens from striated muscle. The purpose of this investigation was to characterize the antigen(s). Polypeptides in homogenates from rat skeletal muscle were separated by SDS-PAGE and trans-blotted to nitrocellulose. Sera from six patients with MG and thymoma stained a large (molecular weight greater than 500 kD) polypeptide, while no staining was observed with sera from 20 non-thymoma MG patients. Titin is one of the large (greater than 500 kD) polypeptides of striated muscle and the antibody containing MG sera have antibodies that bind to titin in a preparation of myofibrillary proteins from rabbit skeletal muscle. The staining pattern is identical to that obtained with antiserum to titin, showing that the antigen has the same electrophoretic mobility as titin. Antibodies from the sera of the patients with MG and thymoma, affinity-purified on the large polypeptide, reacted with skeletal muscle sections in a cross-striational pattern, near the A/I band junction but within the I band, corresponding to the localization of one of the epitopes of titin. Our findings therefore indicate that the muscle antibodies found in the sera from some MG patients with thymoma are directed against titin. PMID- 2242610 TI - Prolonged circulation of immune complexes due to various altered immune functions contributes to nephritis in MRL/lpr mice. AB - To gain some insight into the pathogenesis of proliferative lupus nephritis in MRL/lpr mice we investigated the kinetics of removal of immune complexes from the circulation, the carrier state of blood cells, the uptake of complexes by the mononuclear phagocyte system, and the localization of complexes in kidneys. In nephritic MRL/lpr mice challenged with a subsaturating dose of radiolabelled complexes (2.5 mg bovine serum albumin-anti-bovine serum albumin) liver uptake was profoundly decreased, removal of circulating complexes was delayed, and 12-h kidney localization of complexes was enhanced 7.3-fold, in comparison to control mice. The findings were not encumbered by differences in complement concentration and most likely are attributable to various altered immune functions: spontaneous polyclonal activation of B cells, enhanced production of endogenous immune complexes, delayed removal of complexes from the circulation, and decreased uptake of complexes by the mononuclear phagocyte system. In concert, such altered functions contribute to prolonged circulation of complexes to result in their enhanced deposition in the microcirculation. PMID- 2242611 TI - Adjuvant-induced arthritis in rats. Evidence that autoimmunity to homologous collagens types I, II, IX and XI is not involved in the pathogenesis of arthritis. AB - We examined the sera of arthritic outbred Wistar and Sprague-Dawley rats and inbred Fisher 344 and Wistar-Lewis rats for autoantibodies to rat type I, II, IX and XI collagens following the induction of arthritis with mycobacteria (MTB). Although many sera collected over an extended time were assayed in addition to acid eluates of arthritic joints, convincing evidence for autoimmunity to collagen could not be demonstrated. Instead, modest non-specific reactions were observed to collagen, irrelevant proteins, and buffer-treated plastic microtitre wells. In contrast, antibodies to purified protein derivative (PPD) were detected in the sera of rats developing adjuvant-induced arthritis, and antibodies to type II collagen, in the sera and joint eluate of rats developing experimental collagen-induced arthritis. Lastly, delayed-type hypersensitivity responses to collagen could not be detected, nor could adjuvant-induced arthritis be attenuated by soluble collagen injected intravenously before challenge with MTB. We conclude that adjuvant-induced arthritis and experimental collagen-induced arthritis are distinct models of rheumatic disease and that autoimmunity to collagen is neither prevalent in adjuvant-induced arthritis nor necessary for its pathogenesis. PMID- 2242613 TI - Macrophage procoagulant activity as an assay of cellular hypersensitivity to gluten peptides in coeliac disease. AB - Gluten and casein digests were tested for their ability to induce a cellular immune response on peripheral blood mononuclear cells (PBM) obtained from coeliac patients as well as healthy volunteers and disease control patients using the macrophage procoagulant assay. PBM from coeliac patients who had been on a gluten free diet for less than 2 years responded strongly to gluten peptides, while coeliac patients at diagnosis or who had maintained a strict gluten-free diet for longer than 5 years showed weaker responses. PBM from healthy volunteers did not respond to gluten or casein peptides, whereas those from patients with Crohn's disease displayed weak reactivity to gluten and casein peptides. Our study using the macrophage procoagulant assay confirms previous findings that lymphoid cells from patients with coeliac disease exhibit a specific cellular immune response to gluten. This assay represents an alternative measure for cell-mediated immunity and is technically much simpler than the previously described leucocyte migration inhibition assay. Macrophage procoagulant activity is measured using a simple plasma recalcification time assay or spectrophotometrically using commercially available chromogenic substrates. PMID- 2242612 TI - Participation of eosinophils in the toxic oil syndrome. AB - The participation of eosinophils in the Spanish toxic oil syndrome (TOS) was investigated. Eosinophil infiltration and degranulation in tissues from 52 patients with the TOS were examined by immunofluorescence staining for the eosinophil granule major basic protein (MBP). Serum MBP levels were determined in sera from 323 patients. Eosinophil infiltration and degranulation were found in several tissues, especially during the acute phase of the TOS, and serum MBP was significantly elevated during all phases of the disease, suggesting that eosinophils play a role in the pathogenesis of the TOS. PMID- 2242614 TI - The effect of recombinant interferon-alpha on lymphocyte subpopulations and HLA DR expression on liver tissue of HBV-positive individuals. AB - Interferon-alpha (IFN-alpha) has been reported to be beneficial in the treatment of chronic active hepatitis occurring as a result of hepatitis B virus (HBV) infection. Treatment with IFN-alpha has been proposed as a means of reducing the high rate of allograft infection in clinical liver transplantation in patients transplanted for HBV-related chronic active hepatitis and cirrhosis who are positive for hepatitis B surface antigen (HBsAg). We obtained resected whole livers from two groups of patients who received liver transplants. Group A consisted of 11 patients who were HBsAg+ but were not treated with IFN-alpha, and group B consisted of 10 patients who were also HBsAg+ but received IFN-alpha therapy for 29.4 +/- 5.6 days prior to orthotopic liver transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. The liver tissue was stained with monoclonal antibodies to cell surface antigens unique to different mononuclear cell populations by the avidin-biotin-immunoperoxidase technique to determine the effect of IFN-alpha on the lymphocyte subsets as well as HLA antigen expression on liver-infiltrating mononuclear cells. The number of HLA-DR+ lymphocytes in the liver was significantly increased (P less than 0.005) within the portal areas in group B compared with that found in group A (84 +/- 14 versus 33 +/- 5 per one high-power field). Moreover, the intensity of the HLA-DR antigen expression on lymphocytes in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in group B than in group A. The number of natural killer (NK) cells was increased in the portal areas (P less than 0.05) of group B compared with group A. These alterations in the lymphocyte and NK cell populations present in the liver in response to IFN-alpha therapy presumably reflect an IFN-alpha-induced enhancement of the immune response to virus-infected cells. PMID- 2242615 TI - Characterization of homologous restriction factor (HRF20) in human skin and leucocytes. AB - Homologous restriction factor with a molecular weight of 20 kD (HRF20) is a membrane protein that inhibits assembly of the membrane attack complex of homologous complement. Distribution of HRF20 in normal human skin was studied. The plasma membrane of keratinocytes was stained, and the intensity of the staining pattern was higher in the basal cell layer than in the granular layer. Endothelial cells of blood vessels in the dermis were also stained. The molecular weight of HRF20 on erythrocytes and epidermis is 16 kD, determined by Western blot analysis. Those of polymorphonuclear cells and lymphocytes appeared as two bands, a major band of 20 kD and a minor band of 16 kD. Susceptibility of HRF20 to phosphatidylinositol-specific phospholipase C (PIPLC) was examined. After PIPLC treatment of the sections, HRF20 was not detected on the epidermis and was very slightly expressed on the blood vessels. These results indicate that HRF20 attaches to keratinocytes and blood vessels via phosphatidylinositol, regulating the formation of membrane attack complexes of homologous complement on the cell membrane. PMID- 2242616 TI - Complement, complement activation and anaphylatoxins in human ovarian follicular fluid. AB - Functionally active complement was sought and detected in human follicular fluids obtained during the pre-ovulatory period. All the functional complement activities tested, including total haemolytic complement, classical pathway activity and alternative pathway activity were present in nine fluids from four different donors with values within the normal serum range. The immunochemical analysis demonstrated the presence of complement factors from C1 to C9, of B and of C1 INH, H, I. Complement anaphylatoxins were found employing RIA techniques in amounts significantly higher than in human plasma, thus demonstrating that follicular fluid complement, at least during the pre-ovulatory period, is partially activated. A possible role for urokinase-like substances in such an activation was indicated by further in vitro experiments. The presence of active complement in follicular fluid can be relevant for the function of the enzymatic multi-factorial mechanism of ovulation. PMID- 2242617 TI - Antibody repertoire against culture filtrate antigens in wild house mice infected with Mycobacterium bovis BCG. AB - Wild house mice (Mus domesticus) captured in a Flemish pigsty were infected intravenously with 4 x 10(6) variable units of Mycobacterium bovis BCG and examined by Western blot analysis for IgG secretion against BCG culture filtrate (CF) antigens. Wild mice showed a marked individual variation in antibody pattern when tested 4, 6 and 8 weeks after infection. Some animals reacted to a wide range of antigens and others only to a limited number. Most wild mice recognized preferentially antigens with molecular weight of 24 kD, 32 kD, 37-38-40 kD, 65 kD and 82 kD, i.e. the major CF antigens known to be recognized by sera from BCG infected inbred laboratory strains, BALB/c, DBA/2, CBA/Ca and C57BL/6. The 32-kD fibronectin-binding protein and the 65-kD heat-shock protein appeared as very immunodominant in wild mice. Furthermore, about 20-25% of the mice reacted strongly with a unique antigen of 35 kD estimated molecular weight, to which the tested inbred laboratory mice did not respond. Monitoring the size of the bacterial population in the spleen indicated that the BCG inoculum did not replicate in wild mice, suggesting that the Bcgr allele is expressed in this population. PMID- 2242618 TI - Cellular immunity in experimental Echinococcus multilocularis infection. I. Sequential and comparative study of specific in vivo delayed-type hypersensitivity against E. multilocularis antigens in resistant and sensitive mice. AB - Species- or strain-related differences in receptivity of intermediate hosts to E. multilocularis larvae could be related to differences in specific cellular immune response of the host. In order to test this hypothesis, we assessed the delayed type hypersensitivity (DTH) to E. multilocularis antigens (EmAg) in mice of three strains differing by their sensitivity (AKR and C57BL.6) or resistance (C57BL.10) to E. multilocularis infection. DTH was determined by measuring in vivo the foot pad response 24 h after an EmAg antigenic challenge. The level of positive response was evaluated in immunized mice; however, a typical DTH response was only observed by immunizing mice with a strong adjuvant schedule. Course of DTH in the immunized mice was shown to be somewhat different in sensitive and resistant mice. The differences were much more marked in mice infected with proliferative E. multilocularis larvae. The levels of the footpad response was significantly higher in resistant mice, although the peak of the reaction was obtained later than in sensitive mice. DTH, expressed by the foot-pad response against EmAg, remained significant for the entire period of observation in sensitive as well as in resistant mice. There was no correlation between receptivity of the murine hosts and levels of specific antibodies against EmAg. These results suggest a relationship between resistance to E. multilocularis infection and intensity and/or course of DTH in mice. The resistance could be mediated by some particularities of the in situ cellular immune response in the periparasitic granuloma. PMID- 2242619 TI - Cellular immunity in experimental Echinococcus multilocularis infection. II. Sequential and comparative phenotypic study of the periparasitic mononuclear cells in resistant and sensitive mice. AB - Cellular immune responses have been shown to be associated with differential evolutions of E. multilocularis infection in intermediate hosts. A relationship between course of delayed-type hypersensitivity (DTH) against parasitic antigens and receptivity of murine strains has been demonstrated recently. The aim of this study was to correlate resistance and sensitivity to E. multilocularis infection with the phenotypic patterns of cells within the periparasitic granuloma. Evolution of the ratios, macrophages/T lymphocyte and Ly1/Ly2 T lymphocytes, was associated with the receptivity of the strains. Persistence of numerous L3T4 + T lymphocytes and low numbers of macrophages and Ly2 + T lymphocytes were observed in the 'resistant' C57BL.10 mice. Comparison of the results with course of the DTH against E. multilocularis antigens showed that the particular phenotypic pattern observed in resistant mice was associated with a particular profile of DTH after infection. These results and similar observations in human alveolar echinococcosis suggest that cell composition of the periparasitic granuloma might be of crucial importance in controlling the spontaneous development of E. multilocularis larvae in the intermediate host. PMID- 2242620 TI - Intra-articular immunization induces strong systemic immune response in humans. AB - There is no information available about immunological interactions between the synovial tissue compartment and systemic immunity in health and in disease. The aim of the present study was to evaluate effects of intra-articular immunization on the systemic immune responses in humans. Control subjects were immunized with the same dose of immunogen subcutaneously. Peripheral blood lymphocytes were analysed by spot-ELISA with respect to numbers of immunoglobulin-producing cells and antigen-specific antibody-secreting cells before and 1 week after immunization. Serum and salivary antibody levels were measured by an ELISA before and 14 days after the antigenic exposure. In addition, serum levels of interleukin-6 (IL-6) were analysed before and after immunization. The results indicate that the influenza virus antigen deposited in the joint space induces strong systemic antibody response of IgG, IgA and IgM classes. This response is significantly higher (P less than 0.05) than that of control subjects immunized subcutaneously. In contrast, no significant differences were detected between intra-articularly and subcutaneously immunized subjects with respect to mucosal immune responses. Increased serum levels of IL-6 were observed 1-2 weeks after the vaccination in both experimental groups. We conclude that human joints possess very efficient antigen-presenting properties enhancing systemic B cell reactivity. PMID- 2242622 TI - Legal issues related to the right to die: implications for nursing education. PMID- 2242623 TI - [Distribution of skeletal muscle involvement in myotonic dystrophy--a computed tomographic study]. AB - The computed tomography (CT) scan was performed on 8 myotonic dystrophy (MD) and 3 congenital myotonic dystrophy (CMD) patients on the following seven levels; the jaw, the neck, the shoulder girdle, the abdomen, the pelvic girdle, the thigh and the lower leg. Muscle atrophy was shown as low density areas or a reduction in the cross-sectional area of the muscles. The earliest finding in the disease was severe atrophy of the sternocleidomastoid and mild atrophy of the masseter and the pterygoid medialis. In addition, spinal, abdominal wall and lower leg muscles were involved. The distal muscles were more markedly affected than the proximal in the lower limbs. These changes were characteristically observed in cases without apparent muscle symptoms. Levator scapulae, psoas major, rectus femoris, peroneal longus et brevis and tibialis posterior were relatively well preserved and were even hypertrophic in some cases. The shoulder girdle muscles were more markedly affected than the pelvic girdle muscles. There was no substantial difference in the CT findings between MD and CMD. PMID- 2242621 TI - Transforming growth factor-beta 1 inhibits activation of macrophage cell line RAW 264.7 for cell killing. AB - Transforming growth factor beta-1 (TGF-beta) is a multi-potent immunoregulatory peptide that has effects on numerous cell types. Here we report that human TGF beta inhibits the activation of the macrophage cell line RAW 264.7 for killing of the L1210 tumour cell line. RAW 264.7 cells, like normal macrophages, require sequential interaction with priming and triggering stimuli for full activation of cytolytic activity. TGF-beta inhibits this cytotoxicity in a dose-dependent manner at both the priming and the triggering stage. Addition of as little as 1 ng/ml TGF-beta when added with either the priming signal, recombinant interferon gamma (IFN-gamma), or the triggering signal, bacterial lipopolysaccharide (LPS), completely abrogated tumouricidal activity. Incubation with TGF-beta also inhibited the morphological changes normally observed in activated RAW 264.7 cells. However, TGF-beta was unable to inhibit the cytotoxic activity of RAW 264.7 cells against the target cell line WEHI 164, which is sensitive to tumour necrosis factor. In contrast to the effects on cytotoxic activity, the cytostatic activity of activated RAW 264.7 cells was not inhibited by TGF-beta at doses of up to 5 ng/ml. In addition, pretreatment of the L1210 target cells with TGF-beta made them refractory to both the cytostatic and cytotoxic effects of RAW 264.7 cells. These data suggest that TGF-beta may be an important mediator in the regulation of macrophage tumouricidal activity. PMID- 2242624 TI - [Cerebrovascular disease in the elderly--clinical study of 31 cases with acute intracerebral hemorrhages]. AB - Thirty-one consecutive cases of intracerebral hemorrhage (ICH) in the elderly (over 70 years at the onset) were reported with special reference to neurological evaluations, prognosis and mortality in the acute phase. There were 11 men and 20 women with ICH, who were admitted to the Yokufukai Geriatric Hospital within 24 hours after the onset of ICH. Their ages at the onset ranged from 71 to 93 years with a mean of 81.1 years. The lesion location showed 5 cases with thalamic hemorrhage, 4 cases with putaminal hemorrhage, 6 cases with subcortical hemorrhage, 7 cases with cerebellar hemorrhage, 8 cases with mixed hemorrhage and 1 case with unclassified hemorrhage. 61.3% of all cases showed the onset during daytime but the remaining awoke in the morning with their symptoms or had the onset from the stage of the bedridden state. The classical prodromal symptoms headache and nausea or vomiting were found in 30% and 54.8%, respectively. Two cases with cerebellar hemorrhage were accompanied by vertigo. Twenty-four patients had consciousness disturbance at admission. There were 18 cases with right or left hemiparetic symptoms, 5 cases with tetraparesis, and 5 cases without motor dysfunction. The remaining already had hemiparesis due to old stroke. Patients with mixed hemorrhage usually exhibited conjugate deviation. In 9 of 31 cases there were mental symptoms such as wandering or night delirium. The 30-day mortality rate was 64.5% and sixty-five percent of them died within 6 days after the onset of ICH. Consciousness at admission was the overwhelming predictive factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242625 TI - [Local alcoholisation treatment of spasmodic torticollis]. AB - Idiopathic spasmodic torticollis is a type of focal dystonia. Major muscles which rotate the neck are M. sternocleidomastoideus (SCM) and M. splenius capitis (Spl) on both sides. In torticollis patients, its clinical characteristics could be understood as a vectorial summing up of tonus in bilateral SCM and Spl at rest. There is not any curative treatment for dystonia yet. A variety of medications and many types of surgical interventions have been tried without consistent or satisfactory results. In recent days local injection of botulinum-A toxin has shown to be effective in weakening focal dystonias. We used pure ethanol for local injection. Fourteen patients aged between 20-77 years (mean 48.9) were treated by alcoholisation. Disease duration ranged from 5 months to 12 years (mean 4.9 years). All had torticollis alone or had segmental dystonia containing spasmodic torticollis. Patients were recorded electromyographically using surface electrodes to make sure which neck muscles were hypertonic, and were rated before and after treatment according to the stages (0; normal-5; most severe). On the bases of these recordings the two most active muscles were selected for injection. Into the motor point of these muscles 1 ml of 1% lidocaine, and then the same dose of 99% ethanol were injected. This procedure was repeated on the mean ten times (6-14 times) every other week. The number of times of injection was decided in each case. Using the paired Student t test, there was a significant (p less than 0.01) improvement of the stage for the patients after injection, with a mean of 3.7 before treatment and 2.3 after treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242626 TI - [Auditory brainstem response and somatosensory evoked potential in Machado-Joseph disease in Japanese families]. AB - To clarify physiological aspects of Machado-Joseph disease (MJD), we studied auditory brainstem response (ABR) and somatosensory evoked potential (SEP) in 17 clinically diagnosed patients with MJD aged 32-64 in Japanese families. ABR was recorded in 13 patients. In 8 patients, ABR were abnormal. In 5 patients, the latency of I wave was normal, but other waves could not be evoked. In the other 3 patients, I-III interpeak latency was prolonged. SEP was recorded in 15 patients. In SEP of median nerve, 11 patients had abnormal findings, and SEP of posterior tibial nerve revealed abnormal findings in all 15 patients. In all patients, responses from Erb's point and popliteal fossa were normal in latency, but other peaks were low in amplitude or absent, and the latency and central conduction time (CCT) were prolonged. The result of ABR indicated the involvement of the brainstem auditory pathways in MJD, and the result of SEP suggested that somatosensory pathways, particularly central pathways, would be involved in the disease process. ABR and SEP can be potential diagnostic methods for detection of subclinical abnormality in MJD patients. PMID- 2242627 TI - [Gallstone and Parkinson's disease--ultrasound echography study]. AB - Gastrointestinal symptoms caused by autonomic nervous system dysfunction has been well known in Parkinson's disease. This time we had a chance to see a patient with Parkinson's disease associated with acute abdominal pain because of gallstones. This study extended to examine abdominal findings in 79 cases of Parkinson's disease using abdominal ultrasound echography and also studied relationships between echographic findings and age, Hoen-Yahr stage and duration of the illness. Results were as follows: Echographic abnormalities were found 53.2% of the cases. Among them, gallstone was the most frequent findings and the incidence was 29.1% which showed significantly higher than that of the gallstone holding ratio (16.6%) in a age matched Japanese autopsy study. Subsequent findings were renal cyst (16.5%), renal stone (8.9%), liver cyst, portal dilatation and so on. No remarkable relationship was found between Hoen-Yahr stage and gallstone, however good correlation was found between duration of the illness and gallstone. It was concluded that gallstone holding ratio in Parkinson's disease is considerably high compared to that of a age matched Japanese autopsy study, which might be of great use in our daily clinics. PMID- 2242628 TI - [A case of mitochondrial myopathy with mononeuritis multiplex]. AB - A case of mitochondrial myopathy with mononeuritis multiplex was described. A 55 year-old man was hospitalized because of blepharoptosis and muscle weakness. His mother also showed blepharoptosis in her elderly stage of life. He had been healthy until 46 years of age, when he first noticed difficulty of speech, followed by bilateral blepharoptosis, weakness of upper limbs, and sensory disturbance in the left occipital, and left upper and lower extremities. These symptoms progressed slowly. On admission, bilateral blepharoptosis was recognized. Slightly to moderate muscle wasting and weakness were observed in the face, neck, trunk, and extremities. Areflexia was observed in the upper extremities. Paresthesia was observed in the left occipital and left hip, and superficial sensation was impaired in the left upper and lower extremities. Electromyographic examination of extremities showed neurogenic changes in the distal muscles and myogenic changes in the proximal muscles. Motor conduction velocities were normal, but sensory conduction velocities decreased in amplitude on the left upper extremity and were not evoked on the left lower extremity. Muscle biopsy specimen revealed numerous "ragged-red" fibers. Cytochrome c oxidase stain showed a decrease in intensity of staining. A sural nerve biopsy showed slight axonal degeneration and slight loss of nerve fibers. Biochemical analysis on biopsy muscle showed partial deficiency of cytochrome c oxidase activity. PMID- 2242629 TI - [An autopsy case of HTLV-I associated myelopathy (HAM) with adult T-cell leukemia (ATL)]. AB - An autopsy case of HTLV-I associated myelopathy (HAM) combined with adult T-cell leukemia (ATL) was reported. Although HAM and ATL are reported to be caused by an identical virus, a combination of these two conditions is extremely rare. This is the first report of an autopsy of the case. A 42-year-old female born in Kumamoto noticed gait disturbance at age 20. Dysesthesia in her lower limbs and bladder bowel disturbance (BBD) gradually appeared at age 29 and at age 39, respectively, and slowly progressed. Neurological examination revealed spastic paraparesis, sensory disturbance in her lower limbs in all modalities and BBD. Furthermore, titers of the anti HTLV-I antibody were increased both in serum and CSF. She was diagnosed as HAM at this stage. She responded to the oral administration of prednisolone. Ten months after the initiation of prednisolone therapy, a tumor shadow appeared in the right lung and characteristic ATL cells were found in the pleural effusion. She died with respiratory failure. ATL cells were not found either in the peripheral blood or CSF throughout the course of her illness. Autopsy revealed solid tumors in both lungs, liver, kidneys, spleen, thyroid gland and para-aortic lymphnodes, composed of ATL cells with extensive necrosis. The spinal cord showed a marked loss of myelin and axons, and perivascular fibrosis in the lateral and anterior columns. These changes were most severe at the 6th and 7th thoracic segments. No ATL cell was found in the spinal cord. Concerning the sensory system, the posterior root, ganglion and posterior column were preserved, whereas the axonal degeneration was found in the biopsied specimen of the sural nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242630 TI - [MRI pathology of the globus pallidus in a patient with oculogyric crisis and tremor]. AB - A 24-year-old woman developed occasional attacks of oculogyric crisis at the age of 18. She also suffered from postural tremor, dystonic gait, pyramidal tract signs, and peripheral nerve damages. No history of encephalitis was elicited. Nerve conduction velocity revealed decreased velocity and amplitude. Needle electromyography showed a neurogenic pattern. Sural nerve biopsy showed marked Wallerian degenerations. Muscle biopsy revealed small grouped atrophies. It was unlikely that she suffered from juvenile Parkinsonism, and we failed to obtain an evidence of neuronal intranuclear inclusion disease. Recently, Furumoto et al. reported a similar case who developed oculogyric crisis at the age of 12. So far, some authors have reported about changes of MRI image in the putamen and the substantia nigra in extrapyramidal movement disorders. However, few have paid attention to the changes of the pallidum. The most characteristic finding in the present case was the restoration of signal intensity of the globus pallidus on T2 weighted high-field MRI. It is known that pallidal damages produce dystonic disorders. However, the exact role which the pallidum played in pathogenesis of our patient's signs and symptoms is unknown at now. PMID- 2242631 TI - [Two cases of HTLV-I associated myelopathy (HAM) complicated with Sjogren's syndrome, T-lymphocyte alveolitis and arthropathy]. AB - Two cases of HTLV-I-associated myelopathy (HAM) complicated with Sjogren's syndrome (SjS), T-lymphocyte alveolitis and arthropathy were reported. Case 1 was a 55-year-old woman. Since 40 years of age she had been suffering from repetitive pulmonary infection. She also noted polyarthralgia since 42 years of her age and was diagnosed as SjS at her age 43. She developed gait disturbance since April 1988. Case 2 was a 65-year-old woman. She began to have gait disturbance at 62 years of age. A right knee joint pain started in December 1988. The two cases have the following features in common: 1. The diagnosis of HAM is definite because of pyramidal signs and positive anti-HTLV-I antibody in both serum and cerebrospinal fluid. 2. The histological findings of the minor salivary glands are compatible with SjS. 3. Differential cell count in bronchoalveolar lavage fluid (BALF) showed an increase in lymphocytes which suggested the presence of clinical or subclinical T-lymphocyte alveolitis. 4. A mono-or polyarthropathy is observed. These findings are suggestive that HAM is not the disease restricted within the central nervous system but the disease with systemic involvement which may be caused by the activated T-lymphocytes. Thus the two cases are interesting for the understanding of the pathogenesis of HAM. PMID- 2242632 TI - [Intracranial multiple granuloma preceded by rheumatic disease--a case report]. AB - In 1980, a 38-year-old man had remittent fever, swelling and arthralgia of the knee, ankle and wrist joints, as well as visual disturbance due to bilateral iritis. On his admission to our hospital, his laboratory data showed neutrophilia, normocytic normochromic anemia, hepatomegaly, hepatocellular damage, and a strongly positive RA test. All the microbiological examinations were negative. Thirty mg of prednisolone improved his symptoms and abnormal laboratory findings. Due to persistent mild arthralgia, he had continued to take 5-10 mg of prednisolone and analgesics until 1985 when he was readmitted to our hospital. In 1983, he began to complain of a steady pain around his left eye, and he sometimes had double vision. In 1985, he began to complain of decreasing left visual acuity and sensory disturbance in his left face in addition to pain in and around the eye. On his 2nd admission to our hospital, the neurological examination revealed involvement of the 2nd and 3rd cranial nerves and the 1st branch of the 5th cranial nerves of the left side. Laboratory data showed a positive RA test with RAHA titer at 1:320 and IgM at 216 mg/dl, but he had no joint deformities. The computed tomography (CT) of the brain demonstrated a high density mass of his left cavernous sinus extending to the left orbital apex. The prescription of the high dose of prednisolone (100 mg/day) relieved ophthalmic pain and improved visual acuity and neurological involvement within a week. Prednisolone was then gradually decreased to 10 mg. In 1986, he had partial and complex partial seizures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242633 TI - [A case of hemiballism successfully treated by sulpiride, caused by lesions of the striatum]. AB - A case of hemiballism caused by infarction in the left striatum on MRI was reported. Hemiballism is generally associated with lesions in the subthalamic nucleus. However, hemiballism occasionally occurs as a result of lesions outside the subthalamic nucleus. Hemiballism is a benign condition with spontaneous recovery in most cases, but hemiballism caused by lesions outside the subthalamic nucleus is reported to tend to persist for a long term. In our case without involvement of the subthalamic nucleus, hemiballism so far continued for three months since the onset. Successful pharmacological treatments of ballism with haloperidol or phenothiazines were well known. In our case, the treatments of ballism with these drugs were unsuccessful due to drug-induced hepatic dysfunction. Instead of these drugs, ballism was improved by administration of 150 mg of sulpiride per day with no side effects. Sulpiride may be beneficial for persistent hemiballism caused by the extra subthalamic lesions. PMID- 2242634 TI - [A new family of Machado-Joseph disease--an abnormal decrease in signal intensity of the putamen in magnetic resonance imaging]. AB - The propositus (case 1) was a 40 year-old man. He had begun to note unsteady walking at age 26. He was found to have cerebellar ataxia and pyramidal signs in addition to minor features such as progressive external ophthalmoplegia, gaze nystagmus, bulging eyes, intention fasciculation-like movements of facial and lingual muscles, and limb dystonia. These findings were categorized into type II form of the disease. One sister (case 3) aged 37 years, and one brother (case 4) aged 44 years of the propositus had also type II form of the disease. His uncle (case 2) had the same cerebellar and extrapyramidal signs accompanied with peripheral nerve signs such as muscle wasting, weakness, hypo-tonus and decreased deep tendon reflexes, and a diagnosis of type III form of the disease was made. In the T2-weighted magnetic resonance imaging (1.5 T, TR 2000 or 3000 msec, TE 120 msec) of the three patients (case 1, 3 and 4), dorsolateral part of the putamen showed decreased signal intensity. Although hypo-intensity of the putamen is often observed in normal elderly people over 50 years old, it is considered to be abnormal when it exists in relatively young people as in this family members. PMID- 2242635 TI - [Acute transverse myelitis associated with ECHO-25 virus infection]. AB - A case of acute transverse myelitis associated with ECHO-25 virus infection was reported here with a brief review of the literature. The patient was a 42-year old house wife. Without any antecedent symptoms, weakness and paresthesia of bilateral lower extremities, and sphincter disturbance developed suddenly. Neurological examination revealed paraplegia of both legs, hyperreflexia of lower extremities, bilateral positive Babinski sign and impairment of all sensory modalities below Th4 level. No abnormality was found in myelography and CT myelography. Abnormal intensity area was found in lower cervical spinal cord on MRI. Serum antibody titer to ECHO-25 virus was elevated in the convalescent stage (X4096), and 7 month later from the onset of neurological symptoms, high value was continued (X128). We diagnosed her illness as acute transverse myelitis complicating ECHO-25 virus infection. In the literature, only 3 cases of transverse myelitis following ECHO virus infection (type 2, 5, 19) were found. This case seemed to be the first case of transverse myelitis associated with ECHO 25 virus infection. PMID- 2242636 TI - [A case of cranial polyneuropathy presenting with prominent facial diplegia, elevated serum Borrelia burgdorferi antibody and lymphocytic pleocytosis]. AB - A 54 year-old male patient developed acute cranial polyneuropathy including prominent facial diplegia and radicular++-neuritis. He was proven to have lymphocytic pleocytosis, and elevated serum Borrelia burgdorferi antibody to X800 (normal; less than X200). A diagnosis of typical early neuro-borreliosis was made after these clinical and laboratory findings. This case is the first neuro borreliosis showing the triad of neurological manifestations (meningitis, cranial neuritis, radicular++-neuritis) in Japan. It is concluded that neuro-borreliosis should be considered to be a cause of acute cranial polyneuropathy, particularly of facial diplegia, even if the patient has no apparent history of a tick bite. PMID- 2242637 TI - [A case of transient bilateral primary oculomotor nerve paresis associated with head injury]. AB - A 13-year-old boy, with no past medical history, was admitted after a car accident on October 29, 1989. On admission, he was alert. Physical examination revealed a bruise on the left frontal region, a fracture of right clavicula and right hemopneumothorax. He was treated with respirator due to dyspnea. On November 1, 1989, he was removed from respirator and expressed diplopia. Neurological examination showed bilateral ptosis, mild anisocoria, normal light reflex and horizontal gaze nystagmus in lateral gaze. Both eyes were deviated outward slightly in the primary position and showed inability to converge. The external ocular movements of both eyes were mildly limited in elevation and adduction. Ataxia was observed in bilateral upper extremities. Deep reflexes were normal and no pathological reflexes were observed. Brain CT scans showed no abnormality. On November 6, 1989, his ptosis and diplopia improved. On November 8, he was completely recovered. A magnetic resonance imaging on November 10 revealed no abnormality. We suggested that transient dysfunction of midbrain associated with head injury might cause transient bilateral primary oculomotor nerve paresis, nystagmus and ataxia. PMID- 2242638 TI - [Brainstem ptosis (midbrain ptosis) associated with mesencephalic hemorrhage]. AB - We reported a patient with a brainstem ptosis (midbrain ptosis) associated with mesencephalic hemorrhage. A 57-year-old woman had the sudden onset of bilateral blepharoptosis and diplopia. On admission, computed tomography of the brain and magnetic resonance imaging disclosed a small hematoma in the left tegmentum of midbrain. She had no past history of hypertension of head trauma. Cerebral angiography gave no additional informations. The lesion involving the central caudal subnucleus of IIIrd nerve nucleus may be responsible for the bilateral ptosis, since this finding is consistent with current models of oculomotor organization in monkeys (Warwick 1953). PMID- 2242640 TI - Stuttering. PMID- 2242639 TI - [Intramedullary spinal cord metastasis documented by MR imaging]. AB - A 63-year-old woman with progressive paraparesis was found to have an intramedullary spinal cord metastasis from the primary rectal cancer. Myelography and post myelography CT showed an enlargement of the spinal cord at level of the sixth to seventh thoracic vertebra. MR imaging disclosed a localized mass in the spinal cord at the same level. T2-weighted images showed an oval high signal intensity area with central low intensity, and gadolinium-DTPA-enhanced T1 weighted images demonstrated a ring enhancement. Histological examination of the spinal cord revealed an intramedullary spinal cord metastasis with intra-tumorous necrosis at T7 to T8 cord level. PMID- 2242641 TI - Clinical management of port-wine stain in infants and young children using the flashlamp-pulsed dye laser. AB - The flashlamp-pulsed dye laser (FLPDL) at 585 nm, a wavelength well absorbed by oxyhemoglobin, causes highly selective vascular injury. In addition, the 450 microsecond pulse duration produced by this laser approximates the thermal relaxation time for dermal blood vessels thereby confining the energy to the target. This new laser effects excellent lightening of port-wine stain (PWS) in infants and young children without the adverse complications of hypertrophic scarring, permanent pigmentation abnormality, or textural changes, complications often seen with conventional laser systems. The FLPDL now permits treatment of this patient population expected to gain the most benefit from early laser therapy in a much safer manner, before the psychological complications of being a "marked" person develop. The purpose of this report is to: (1) describe the theoretical considerations behind achieving selective removal of PWS that can be understood and used by a nonsurgically-oriented practitioner; and (2) describe the practical application of the device used in the clinical management of infants and young children. PMID- 2242643 TI - Blood pressure in children as determined under office conditions. PMID- 2242642 TI - Neurologic complications in chronic renal failure: a retrospective study. AB - We have retrospectively examined 324 patients with chronic renal failure and evaluated the probable underlying causes of neurologic complications, laboratory data and therapeutic interventions. The common neurologic problems in our patients were alterations in consciousness (40.7%) and convulsions (35.1%). When BUN concentration was above 135 mg/dl and creatinine clearance was below 8 m/min/1.73 m2, alteration of consciousness was observed and when BUN concentration was 200 mg/dl and creatinine clearance was below 7 m/min/1.73 m2, abnormal convulsives appeared. Changes in deep tendon reflexes and pathologic reflexes were associated with hypertension. All of the patients with cortical atrophy using computerized cranial tomography aluminum hydroxide at least for 18 months, and six of them had hemodialysis. Fourteen patients who underwent dialysis developed convulsions and were thought to have disequilibrium syndrome. These findings are consistent with the suggestion that the metabolic and biochemical derangements associated with CRF may be particularly detrimental to the still developing CNS of the child. PMID- 2242644 TI - Aerococcus viridans infection. Case report and review. PMID- 2242646 TI - Hepatic Burkitt lymphoma. Presentation with extremely rapid growth. PMID- 2242645 TI - Urinary tract infection in the male caused by Staphylococcus epidermidis associated with diverticulum of the bladder. PMID- 2242648 TI - "The rushes." A migraine variant with hallucinations of time. PMID- 2242647 TI - Clinical Fitz-Hugh-Curtis syndrome in an adolescent. Ultrasonographic findings. PMID- 2242649 TI - Zoster-like eruption associated with herpes simplex virus infection in children. PMID- 2242650 TI - Toxicity from topical administration of diphenhydramine in children. PMID- 2242651 TI - Epidemiologic aspects of toilet training. PMID- 2242652 TI - Sinusitis. PMID- 2242653 TI - Diseases that mimic meningitis. PMID- 2242654 TI - Scientific perspectives from the Sixth International Conference on AIDS. PMID- 2242655 TI - Treatment of Kawasaki disease. AB - The epidemiology, etiology, diagnosis, and treatment of Kawasaki disease are reviewed. Kawasaki disease, or mucocutaneous lymph node syndrome, is an acute, usually self-limiting, multiple-organ-system disease of childhood that occurs both epidemically and endemically worldwide. The etiology of the disease is unknown but may involve an infectious agent. To be diagnosed, a patient must be febrile for at least five days and show four of five additional clinical features: bilateral conjunctivitis, changes in the oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. The most important complications are cardiac; patients may develop aneurysms or thrombosis of the coronary arteries or myocarditis. Other complications include arthritis, conjunctivitis, and hydrops of the gallbladder. Aspirin, intravenous immune globulin, corticosteroids, and antithrombotic agents have been investigated for use in the treatment of Kawasaki disease with varying results. Current recommendations suggest therapy with aspirin 80-100 mg/kg/day every six hours for the first 14 days after diagnosis and intravenous immune globulin 400 mg/kg/day for the first four days. The dose of aspirin should then be reduced and continued for six to eight weeks if no coronary artery abnormalities are present. Treatment guidelines for Kawasaki disease are being refined. Current evidence supports early use of aspirin and intravenous immune globulin to prevent cardiac complications. PMID- 2242656 TI - Management of elevated intracranial pressure. AB - The pathophysiology, clinical manifestations, monitoring techniques, and management of elevated intracranial pressure (ICP) are reviewed. The use of barbiturate coma to treat ICP is discussed in detail. Elevated ICP can be associated with severe head injuries and diseases of the central nervous system such as brain tumors and stroke. Symptoms of elevated ICP may be difficult to distinguish from symptoms of other disease states. ICP monitoring techniques such as the intraventricular catheter and the Camino fiber optic system are useful for determination of ICP elevations before any changes in vital signs or neurological status occur. Conventional treatment and control of ICP elevations includes general and physiologic management (cerebrospinal fluid removal, fluid restriction, controlled hyperventilation, sedation, and elevating the patient's head) and pharmacologic management. Osmotic diuretics, (e.g., urea, mannitol, glycerol) and loop diuretics (e.g., furosemide, ethacrynic acid) are first-line pharmacologic agents used to lower elevated ICP. Corticosteroids may be beneficial in some patients. Patients with elevated ICP refractory to conventional treatment may benefit from therapy with high-dose barbiturates. Pentobarbital has been used in the majority of the clinical studies. Pentobarbital serum concentrations should be determined every 24-48 hours when a patient is in a barbiturate coma because pentobarbital clearance increases with continued high-dose therapy. The treatment of elevated ICP requires aggressive therapy and intensive monitoring. In patients whose ICP is refractory to conventional therapies alone, survival rates have been improved by combining high dose barbiturates with conventional therapies. PMID- 2242657 TI - Influence of chewable sucralfate or a standard meal on the bioavailability of naproxen. PMID- 2242658 TI - Comparison of serum aminoglycoside concentrations produced by two infusion methods. PMID- 2242659 TI - Anticonvulsant drug withdrawal in seizure-free patients. PMID- 2242660 TI - Using population-based serum drug concentration cutoff values to predict toxicity: test performance and limitations compared with Bayesian interpretation. AB - The use of population-based serum drug concentration cutoff values for several commonly monitored drugs as tests to distinguish toxicity from nontoxicity was studied. Serum drug concentration and response data published in studies of theophylline, digoxin, aminoglycosides, vancomycin, and procainamide were analyzed to determine the prevalence of toxicity in each group of patients. Serum drug concentration cutoff values were then varied, and the following performance characteristics of the cutoffs as tests for predicting toxicity were calculated for each value: sensitivity, specificity, likelihood ratio, predictive value, and ratio of net consequences. At commonly accepted cutoff values, sensitivity was lower than desirable, positive predictive values were less than negative values, and the ratio of net consequences indicated that false-negative errors are implicitly weighted as more risky than false-positive errors. As the cutoff for each drug was increased, specificity increased but sensitivity decreased, positive predictive values increased but negative predictive values decreased, and the ratio of net consequences increased. Therapeutic drug monitoring would improve if practitioners and laboratorians collaborated to (1) conduct prospective studies of the test performance characteristics of drug concentrations, (2) estimate the pretest probability of toxicity for each patient, (3) combine the pretest estimate with the test characteristics to make a posttest estimate, and (4) develop a more patient-specific, Bayesian approach. PMID- 2242661 TI - Criteria for use of ciprofloxacin for infections in adult patients. PMID- 2242662 TI - Monoclonal antibody therapy. PMID- 2242664 TI - Spectrum and multiplicity of infectious complications in patients with AIDS: a microbiological perspective. PMID- 2242663 TI - Deterring the progression of HIV infection. PMID- 2242665 TI - Evaluation and treatment of mental disorders in patients with AIDS. AB - Mental symptoms are common in patients with AIDS. Optimal management involves the identification and treatment of underlying mental disorders rather than symptomatic treatment alone. Organic mental disorders are very frequent in AIDS, particularly with seriously ill patients who are medical inpatients. There is a high priori probability that such common symptoms as agitation, irritability, and insomnia will be caused by an organic mental disorder. Psychopharmacology in the patient with AIDS requires considerable caution. Lower doses and careful surveillance for subtle neuropsychiatric side effects are necessary. Routine medical contact with a compassionate physician may be of inestimable value to the patient in coping with the fear and dread that surround the illness. PMID- 2242666 TI - Diagnosis and treatment of osteomyelitis. PMID- 2242667 TI - Prevention and treatment of viral hepatitis. PMID- 2242668 TI - Psychopathology in later life. PMID- 2242669 TI - Every man desires to live long; but no man would be old. PMID- 2242670 TI - Renal function and the care of the elderly. PMID- 2242671 TI - Alcoholism in the elderly. PMID- 2242672 TI - Age-related changes in postural sway. PMID- 2242673 TI - Hyperkalemia in the elderly. PMID- 2242674 TI - Management of hypertension in the elderly. PMID- 2242675 TI - Current understanding of osteoporosis. PMID- 2242676 TI - Laser-Doppler flowmetry. AB - Laser-Doppler flowmetry is a new method of the continuous and noninvasive measuring of the tissue blood flow, utilizing the Doppler shift of laser light as the information carrier. The method has already proved its potential usefulness in the clinical assessment of blood flow within disciplines such as dermatology, plastic surgery, and gastrointestinal surgery. In experimental medicine, laser Doppler flowmetry has been used in the study of spontaneous rhythmical variations as well as in the study of spatial and temporal fluctuations in human skin blood flow. The method has facilitated further investigations of the nature of blood flow in a variety of tissue types. The method is rapidly spreading to many new applications in microvascular blood flow measurements. Several commercial laser Doppler instruments are available. This review article is a presentation of the state of the art of laser-Doppler flowmetry including theory, technology, and applications. PMID- 2242677 TI - Applications of time-varying magnetic fields in medicine. PMID- 2242678 TI - Orthopoxvirus genetics. AB - Genetic analysis of orthopoxviruses has contributed substantially to our understanding of the functional organization of the poxvirus genome, and individual mutants provide invaluable tools for future studies of poxvirus biology. Deletion and transposition mutants, localized primarily in the termini of the genome, may be particularly useful for studying virus host range and pathogenicity. Numerous drug resistant and dependent mutants provide keys to understanding a wide variety of virus genes. A large number of well-characterized ts mutants, clustered in the center of the virus genome, are taking on an increasingly important role in research on the function of essential poxvirus genes. Genetic characterization of orthopoxviruses has progressed rapidly during the past decade, and one can reasonably anticipate a time when mutants will be available for the study of any poxvirus gene. Considerable progress toward this goal can be achieved through organized attempts to integrate and further characterize existing mutant collections and through the continued isolation and characterization of deletion, drug resistant, and ts mutants using established techniques. The most exciting possibility is that soon techniques will be available for directed mutagenesis to conditional lethality of any essential poxvirus gene. PMID- 2242679 TI - Recombinant vaccinia viruses as vectors for studying T lymphocyte specificity and function. PMID- 2242680 TI - Posttranslational modification of vaccinia virus proteins. PMID- 2242681 TI - Regulation of orthopoxvirus gene expression. PMID- 2242682 TI - The role of telomeres in poxvirus DNA replication. PMID- 2242683 TI - The enzymology of poxvirus DNA replication. PMID- 2242685 TI - Choledochoscopy in management of retained biliary stones and recurrent lesions. AB - Postoperative choledochofiberscopy was performed in 188 patients with retained biliary stones and recurrent lesions. The following entrances to the biliary tract for choledochoscopy were used: the T-tube tract (129 patients), an afferent jejunal limb of a choledochojejunostomy (43), the jejunostomy tube tract of an efferent limb (12), an U-tube tract (2), and a ductal fistula after segmental liver resection (2). 380 choledochoscopic sessions were carried out, 2 sessions on the average for each patient. The overall success rate of stone removal was 90.5%. No mortality was related to this procedure. Eleven patients developed fever and chills after manipulations but all responded to antibiotics. Two patients had perforation of the T-tube tract during the removal of stones and were reoperated on for abdominal drainage. They recovered eventually. Stone extraction with a flexible choledochoscope is a proven procedure. For residual intrahepatic stones, however, a satisfactory entrance into the biliary tree should be provided for subsequent stone removals. We believe that the jejunostomy tube tract of an efferent limb of an afferent jejunal limb of a choledochojejunostomy is a useful entrance for choledochoscopy because it is permanent in meeting therapeutic demands. PMID- 2242684 TI - HDV (delta factor) infection complicated with subacute fulminant hepatitis B. A morphological and immunohistochemical observation. AB - In 75 patients with subacute fulminant hepatitis B (SAFH), HDAg positive liver cells were observed in 14 cases (18.67%) by direct enzyme labelled method. It was found further that HDV (delta factor) infection was an important cause in producing massive necrosis of liver cells and superinfection of HDV with hepatitis B was identified as one of the causes of SAFH. This experiment also showed that the number of HDAg positive cells was in direct proportion to the area of liver necrosis. No obvious lymphocytic infiltrations and cytotoxic phenomena around the necrotic foci and HDAg positive cells could be found, while the cytoplasmic type HDAg positive cells showed distinct degeneration or even atrophy. Hence it was suggested that HDV could be a direct pathogenesis. No obvious characteristic changes in morphology of HDV infection could be found. PMID- 2242686 TI - [Reperfusion induced arrhythmias]. PMID- 2242687 TI - [Diagnostic changes in serum creatine kinase MM isoenzyme sub-bands after the onset of acute myocardial infarction]. AB - The authors quantified the change of CK-MM isoforms in the first available serum sample from 16 patients each with acute myocardial infarction (AMI) and angina pectoris and 16 normal individuals as well. The average MM3/MM1 ratio in the normal group was 0.24 +/- 0.12, in angina group 0.21 +/- 0.13, and in AMI group 0.52 +/- 0.30 (P less than 0.001, as compare with the first two groups). The first blood sample of AMI was obtained in 3.0 +/- 1.9 hours after the onset of chest pain. Half of them (8/16) had a ratio of MM3/MM1 greater than 0.50 and the change occurred as early as 30 min after the attack. In contrast, the total CK and CK-MB in the three groups were within normal limits at the same time, they were 85.8 +/- 24.4 U/L for CK and 3.2 +/- 1.1% for CK-MB in patients with AMI, 66.7 +/- 18.0 U/L, 2.7 +/- 1.6% in angina pectoris and 71.4 +/- 24.5 U/L, 3.0 +/- 1.1% in normal subjects respectively. Accordingly, diagnostic change of CK-MM isoforms was the earliest among the enzymes after the onset of AMI. PMID- 2242688 TI - [Semi-quantitative estimation of serum myoglobin with rapid reverse passive latex agglutination (RPLA) test and its application in the early diagnosis of acute myocardial infarction]. AB - By using monoclonal anti-myoglobin antibodies to sensitize new immunospheres, serum myoglobin (SMb) was semi-quantitatively estimated with a rapid reverse passive latex agglutination (RPLA) test. Its clinical value in the early diagnosis of acute myocardial infarction (AMI) has been evaluated in 56 patients with AMI, 7 of them being observed serially. There are 92 serum specimens of AMI, of which 19 were within 12 hours after the onset of symptoms. Meanwhile, serum specimens of 72 non-AMI patients were observed with the same method. All the specimens above were also quantitated with radioimmunoassay (RIA) and the results were compared with those of RPLA. RPLA test was negative in the specimens below 100 ng/ml (81 specimens) and positive in those above 110 ng/ml (73 specimens). For specimens from 100 to 110 ng/ml, RPLA test could be either positive (9/10) or negative (1/10). This study confirms that RPLA test is a very sensitive indicator for acute myocardial infarction. It can yield a reliable semi-quantitative estimation of SMb within a few minutes. Because of its simplicity, rapidity and practicability. RPLA test is especially convenient for use in emergency room. PMID- 2242689 TI - [Percutaneous balloon exploration and plug closure of arterial duct]. AB - Percutaneous plug closure of arterial duct (AD) was performed on 38 patients, with ages ranging from 6 to 54 years. The inside diameter of AD varied from 3.7 to 11.6 mm and the shunt size of AD was 8-77% of the pulmonary flow. A combined technique was used in the closure operation, which employs a balloon catheter to explore the size of AD as well as its distensibility and a catheter scale to examine the compatibility of the foam plug with the AD to be closed. Total occlusion was achieved in all the 38 cases, the success rate being 100%. Immediately after the procedure, blood oxygen analysis showed an interruption of the left-to-right shunt and the pulmonary artery pressure decreased from 4.71 +/- 0.80 to 3.34 +/- 0.53 kPa (P less than 0.001). Four to 7 days later, the cardiothoracic ratio reduced from 52.8 +/- 4.6 to 49.7 +/- 4.2% (P less than 0.001) and the cardiac index decreased from 6.00 +/- 1.31 to 4.46 +/- 0.80 L/min.m-2 (P less than 0.001). Random color Doppler flow imaging suggested no residual shunts. No major complications were observed in any of the cases and follow-up observations in 1 to 24 months showed no plug displacement or recanalization. IN CONCLUSION: the balloon exploration is able to make certain of the "occlusion diameter" of AD and the scale examination can surely sort out the plug most compatible with the AD to be closed, so that success of every step for the closure is ensured. PMID- 2242690 TI - [Diagnostic evaluation of frequency domain correlative cardiography in patients with coronary heart disease]. AB - Frequency-domain correlative cardiography (FCG) is a new non-invasive technique for diagnosing heart disease. FCG was performed in 110 patients who also underwent coronary cineangiography. 12-lead ECG and treadmill exercise testing to determine its diagnostic role in coronary heart disease (CHD). In the group with CHD 61 had true-positive and 8 false-negative FCG results, while in the group without CHD 30 were true-negative and 11 false-positive. Its sensitivity is 88.4%, specificity 73.2%, correct diagnostic rate 84.3% and predictive value 84.7%. The diagnostic efficacy of FCG is better than those of 12-lead ECG and treadmill exercise test. These results indicate that FCG is a valuable noninvasive method for detecting patients with CHD. PMID- 2242691 TI - [Estimation of systolic pulmonary artery pressure with continuous wave Doppler pressure gradient method: a simultaneous Doppler and catheter correlative study]. AB - To estimate more precisely the systolic pulmonary artery pressure (PASP), continuous wave Doppler pressure gradient method and catheter measurement were performed simultaneously in 85 patients. There were 30 patients with tricuspid regurgitation (TR), 35 with ventricular septal defect (VSD), and 20 with patent ductus arterosus (PDA). For maximal transtricuspid pressure gradient (TRPG) determined by continuous wave Doppler and catheter determined PASP in TR group, the correlation coefficient (r) was as high as 0.99. For Doppler determined PASP (subtracting pressure gradient across PDA from systemic arterial pressure measured by cuff sphygmomanometer) and catheter determined PASP in PDA group, r was 0.95. Doppler determined PASP in VSD group (subtracting pressure gradient across VSD from systemic arterial pressure) also correlated well with catheter determined PASP (r = 0.97). This study demonstrates that continuous wave Doppler pressure gradient method can accurately estimate PASP in patients with TR, PDA, and VSD. PMID- 2242692 TI - [Protective effect of colloidal bismuth subcitrate on gastric mucosal lesion induced by aspirin]. AB - This study was designed to investigate the protective effect of colloidal bismuth subcitrate (CBS) on aspirin-induced gastric mucosal lesion 20 patients with arthralgia were allocated into this study. All of them were free of gastrointestinal symptom and their gastric mucosa were nearly normal under gastroendoscopic observation. The first group of 10 patients received orally aspirin 1.5 qid for 4 days. The second group also of 10 patients was treated with CBS 120 mg qid and after 2 days they received aspirin and CBS simultaneously in the dosage mentioned above for another 4 days. Before and after treatment, the patients of both groups were examined endoscopically. After treatment, the mucosal inflammation was much less in the second group than that in the first group. The prostaglandin E2 concentration of antral mucosa in the first group was reduced significantly after administration of aspirin alone, while that in the second group was slightly increased after a combined treatment of aspirin and CBS. The results demonstrate that CBS is an effective agent in prevention of gastric lesion induced by aspirin and prostaglandin E may be involved in this mucosal protective effect. PMID- 2242693 TI - [Study on urinary function and metabolism of water and electrolytes in primary hypothyroidism]. AB - Water excretion in 16 patients with primary hypothyroidism was lower in amount and more delayed (P less than 0.05) than that in 5 normal controls after acute water ingestion. The mean plasma osmolality of the patients was lower than that of normal controls both before and after water loading. However, the mean urine osmolality was not decreased but rather elevated. The clearance of free water in the patients was lower than that in normal controls before loading, Although the clearance of osmolality in the patients was higher than that in the controls, the difference was insignificant. These two clearance rates were lower than those in the controls after loading. The fractional excretion of sodium (P less than 0.05) and chloride (P less than 0.01) in the patients was significantly higher than that in the controls before loading and both of them remained elevated after loading. Most of the parameters mentioned above improved in 9 patients after treatment with desiccated thyroid. PMID- 2242694 TI - A combined electromyographic and cineradiologic investigation in patients with defecation disorders. AB - Records from 20 patients on whom defecography and electromyography were performed simultaneously because of defecation disorders were analyzed. According to the electromyographic investigation, the patients could be divided into three main groups: 1) normal sphincter reaction; 2) paradoxical sphincter reaction; and 3) combined reaction. Group A was characterized by a marked reduction of muscular activity during emptying and a pronounced closing reflex after emptying. This was followed by return of normal tonic activity. Patients in group B had no relaxation of the sphincters during emptying but a pronounced increased activity in the external sphincter and the puborectalis muscle. They also had severe emptying difficulties at defecography. No closing reflex was seen. In group C the electrical activity in the sphincters increased during moderate straining and when emptying was complete a clear closing reflex was seen. In this study, a dynamic visualization of the defecation together with a registration of electromyographic activity in the striated anal sphincters was performed. It was shown that patients with paradoxical sphincter reaction were lacking a closing reflex after emptying was complete. This has not been reported previously and is important evidence for the paradoxical defecation pattern. It was also shown that the patients with rectoceles had paradoxical sphincter reaction. PMID- 2242695 TI - Perianal abscess and fistula-in-ano in children. AB - The authors present a retrospective review of 40 pediatric patients with perianal abscess and/or fistula-in-ano. The total patient population could be divided clinically into 2 broad groups. The first group consisted of 22 infants younger than 2 years of age, all of whom were males, and 10 of whom presented with recurrences after previous incision and drainage. Of the 14 infants presenting with an abscess, in 12 (85.7 percent), a fistula-in-ano was discovered at surgery. In contrast, in the group of 18 children older than 2 years of age, there were 7 females and 11 males, and fistulas were identified in only 7 of 13 patients (54.8 percent) who presented with abscesses. Surgical treatment consisted of examination under anesthesia and a diligent search for a fistulous tract. Abscesses were primarily saucerized and fistulotomy and cryptotomy of the confluent crypt was performed if a fistulous tract was identified. The only recurrences with this form of treatment occurred in the two immunocompromised patients. PMID- 2242696 TI - Erythrocyte stearic acid desaturation in patients with colorectal carcinoma. AB - The erythrocyte stearic:oleic acid ratio (saturation index) was investigated as a means of differentiating between control subjects (n = 146) and patients with benign (n = 48) and malignant (n = 117) colorectal disease and patients undergoing postoperative follow-up after curative resection (n = 49). Erythrocyte fatty acid profiles were determined by gas liquid chromatography. Neither age, sex, Dukes' stage, nor degree of differentiation of the tumors had a significant effect on the erythrocyte saturation index. The erythrocyte saturation index was lower in patients with primary and recurrent colorectal cancer compared with control subjects and patients with inflammatory bowel disease or benign colonic polyps (P less than 0.0001). The erythrocyte saturation index was not found to be useful in the postoperative follow-up of these patients. Using both saturation index and age as a means of differentiating between patients with primary colorectal cancer and control subjects gave a sensitivity of 67 percent and a specificity of 81 percent. PMID- 2242697 TI - Colostomy irrigation in the elderly. Effective recovery regardless of age. AB - One hundred forty elderly cancer outpatients with colostomy in the authors' rehabilitation department were included in an analysis of the feasibility, effectiveness, and safety of periodic irrigation of remaining colon with lukewarm tap water with the aim of regaining full continence. Sixteen patients did not have a sufficiently long remaining bowel (cecostomy, transverse colostomy) and 17 were considered unsuitable to learn the technique because of advanced neoplastic disease with poor life expectancy, intercurrent disease, or stomal problems. One hundred seven patients were proposed to perform the irrigation: 17 refused to do so with the remaining 90 able to learn the method without problems. Nearly all patients achieved full continence for at least 24 hours. Three patients refused to continue, and nine interrupted for minor complications. The median duration of irrigation in the whole group is 257 days (range, 1 to 2669 days): 32 patients have been irrigating from one to five years, and 9 patients for more than 5 years. Based on these results, we recommend irrigation as standard rehabilitative treatment for elderly patients. PMID- 2242698 TI - Nitrite from inflammatory cells--a cancer risk factor in ulcerative colitis? AB - Elevated levels of luminal nitrite and a lowered luminal pH were found in 77 percent of patients with acute ulcerative colitis. No luminal nitrite was found in healthy control subjects. Nitrites are a secretory product of activated macrophages and neutrophils of the lamina propria, whereas the lowered luminal pH is due to diminished bicarbonate formation by impaired colonocytes. A hypothesis is put forward that nitrites, lowered pH, and bacterial amines are conducive to formation of carcinogenic n-nitroso compounds, which reflect a cancer risk in patients with ulcerative colitis dependent on the type and extent of inflammatory cell activation as well as metabolic impairment of colonic epithelial cells. PMID- 2242699 TI - Passage of a colon 'cast' after anoabdominal rectal resection. Report of a case. AB - The authors report a case of the passage of a total colonic J-pouch "cast" per anus after anoabdominal rectal resection and colonic J-pouch-anal anastomosis. This occurred without development of cuff abscess and was not due to occlusion of the inferior mesenteric artery. This was successfully treated, with preservation of anal function, with resection of the colonic J-pouch by transanal approach. PMID- 2242700 TI - Sexually transmitted diseases of the colon, rectum, and anus. The challenge of the nineties. AB - During the past two decades, an explosive growth in both the prevalence and types of sexually transmitted diseases has occurred. Up to 55 percent of homosexual men with anorectal complaints have gonorrhea; 80 percent of the patients with syphilis are homosexuals. Chlamydia is found in 15 percent of asymptomatic homosexual men, and up to one third of homosexuals have active anorectal herpes simplex virus. In addition, a host of parasites, bacterial, viral, and protozoan are all rampant in the homosexual population. Furthermore, the global epidemic of AIDS has produced a plethora of colorectal manifestations. Acute cytomegalovirus ileocolitis is the most common indication for emergency abdominal surgery in the homosexual AIDS population. Along with cryptosporidia and isospora, the patient may present to the colorectal surgeon with bloody diarrhea and weight loss before the diagnosis of human immunodeficiency virus (HIV) disease. Other patients may present with colorectal Kaposi's sarcoma or anorectal lymphoma, and consequently will be found to have seropositivity for HIV. However, in addition to these protean manifestations, one third of patients with AIDS consult the colorectal surgeon with either condylomata acuminata, anorectal sepsis, or proctitis before the diagnosis of HIV disease. Although aggressive anorectal surgery is associated with reasonable surgical results in some asymptomatic HIV positive patients, the same procedures in AIDS (symptomatic HIV positive) patients will often be met with disastrous results. It is incumbent upon the surgeon, therefore, to recognize the manifestations of HIV disease and diagnose these conditions accordingly. PMID- 2242701 TI - Use of new retractor to facilitate mucosal proctectomy. PMID- 2242702 TI - Dilatation of radiation-induced sigmoid stricture using sequential Savary Guilliard dilators. A combined radiologic-endoscopic approach. PMID- 2242703 TI - Transitional mucosa. PMID- 2242704 TI - Colonoscopic screening. PMID- 2242705 TI - Renal response to furosemide in very low birth weight infants during chronic administration. AB - Renal response to furosemide following initial and chronic doses was investigated in premature infants with bronchopulmonary dysplasia. Seven infants (mean birth weight = 890 +/- 216 g, mean gestational age at birth = 27.7 +/- 2.6 weeks, mean postnatal age at the start of diuretic therapy = 2.7 +/- 0.9 weeks) were studied. Twelve-hour urine collections were performed after the initial dose, and following chronic doses after 1 week and 3 weeks of therapy. Volume of each urine sample was measured and concentrations of furosemide, sodium and creatinine determined. Linear dose-response relationships were found between the logarithm of the urinary furosemide excretion rate and diuretic/natriuretic response (urine output and urinary sodium excretion rate). The furosemide excretion rate required to achieve midrange diuretic and natriuretic responses was significantly greater during chronic dosing than following initial doses, indicating a decrease in renal responsiveness to drug with sustained use. Increasing postconceptional age was associated with a decrease in initial responsiveness to furosemide. These data demonstrate that in premature infants renal sensitivity to furosemide decreases with chronic use as well as with increasing postconceptional age at the start of therapy. The decrease in renal sensitivity to drug with chronic use is of much greater magnitude, and appears to represent renal compensation for drug induced diuresis and natriuresis. PMID- 2242706 TI - Thiopental efficacy in phenobarbital-resistant neonatal seizures. AB - The successful treatment with thiopental (10 mg/kg, i.v.) of 9 severely asphyxiated newborns, under artificial ventilation, with neonatal seizures resistant to phenobarbital, is reported in this pilot study. The clinical and electroencephalogram control of seizures was prompt and resolute. No adverse effect on cardiovascular function (heart rate, blood pressure) was observed. The terminal half-life of thiopental averaged 9 h, the total plasma clearance 0.20 l/h/kg, and the steady-state volume of distribution 3.6 l/h/kg. The kinetic profile of the drug compared to phenobarbital and phenytoin in newborns suggests that its action is quicker and shorter lasting. Thus, from these findings, thiopental may offer a useful and handy approach for the safe and effective treatment of phenobarbital-resistant neonatal seizures. PMID- 2242707 TI - Effect of clonazepam on brain development of mice. AB - Twenty-seven Kun-Ming white mice were divided randomly into three groups of 9 animals. One of these groups served as a control group. Clonazepam (CZP), 0.1 or 0.5 mg/kg/day, was administered by oral gavage for 22 days. The water-maze test was performed before giving CZP and 10 and 22 days later. The step-down test was performed on the 1st and the 2nd day after discontinuing CZP treatment to determine toxic effects on brain development and learning-memory function. Body weights and brain weight were also recorded. Brain development and learning memory function, evaluated by water-maze and step-down tests, were not impaired by CZP. Although there was a trend toward lower weights in the higher-dose group, CZP treatment did not significantly affect either body weight or total or regional brain weight. The results of this study indicate that 4 weeks of treatment with CZP does not impair brain development and learning-memory function in baby mice. PMID- 2242708 TI - Increasing extracellular calcium concentration does not prevent hypotensive effects of verapamil in neonatal swine. AB - Effects of CaCl2 on cardiac function and regional circulatory responses to verapamil (V) infusion were studied in pentobarbital-anesthetized 2-week-old swine. V 100 micrograms/kg (n = 15) or 300 micrograms/kg (n = 15), given as a 2 min intravenous infusion, was repeated after 30 min. Only V was given to 15 of these. The other 15 were given CaCl2 (15 mg/kg) over 2 min, pre-V (protocol A), and over 4 min, 2 min pre-V and during V (protocol B). Positive chronotropic and negative inotropic responses to V were attenuated by CaCl2; hypotensive effects were unaltered. Renal, but not mesenteric and femoral, vasodilation was augmented by CaCl2, CaCl2 alone produced marked positive inotropic and renal vasodilatory effects which contributed to maintenance of the hypotensive effect of V. PMID- 2242709 TI - Effects of prolonged fetal hyperinsulinemia on plasma catecholamines, circulation and oxygen metabolism in utero. AB - The effects of pharmacologic hyperinsulinemia on changes in plasma catecholamines, circulation and oxygen metabolism were examined in fetal sheep. Sequential incremental doses of 0.2 and 0.4 U.kg-1.h-1 of porcine insulin were infused into fetal sheep for 24 h each, for a total of 48 h; pharmacologic fetal insulin concentrations were achieved. Fetal hyperinsulinemia resulted in fetal hypoxemia on the basis of reduced umbilical venous oxygen content. Fetal oxygen extraction increased and oxygen uptake did not change. Prolonged fetal hyperinsulinemia with hypoxemia was also associated with hypoglycemia and a surge in fetal plasma catecholamine concentration. Heart rate and fetal body blood flow also increased. This increased blood flow to the fetal body resulted from increased blood flow to vital organs, including heart and adrenal glands, and insulin-sensitive tissues, including gastrointestinal tract and carcass, without reductions in blood flow to other fetal organs. These changes in regional vascular perfusion maintained oxygen delivery to individual fetal organs similar to values before insulin infusion. We conclude that the ovine fetus has a remarkable ability to compensate for pharmacologic hyperinsulinemia of 48 h duration, which resulted in hypoxemia, hypoglycemia, and a surge in plasma catecholamine concentration, and that appropriate fetal adaptations maintained fetal oxygen consumption and regional oxygen delivery to individual fetal organs. PMID- 2242710 TI - Prolonged infusion of atracurium in an infant. AB - Atracurium is a neuromuscular blocking agent that spontaneously degrades by Hoffmann reaction. This study of a prolonged infusion (7 days) in an infant of 6 months shows an increase in infusion rate requirement from 0.7 mg/kg/h after 96 h of infusion to 1.8 mg/kg/h at the 7th day. The plasma laudanosine levels remained relatively constant (977-1,515 ng/ml) and well below the reported potent convulsive levels during the study despite a 3-fold increase in the atracurium requirement. No side effect or accumulation of the drug was observed. The reasons for the increase in atracurium requirement are discussed. PMID- 2242711 TI - Cerebrospinal fluid and plasma beta-endorphin-like immunoreactivity in full-term neonates and in preterm neonates with and without apnea of prematurity. AB - Beta-endorphin-like immunoreactivity (B-ELI) was measured in cerebrospinal fluid (CSF) and plasma from infants of postnatal age 24 h to 70 days. Three groups were examined: 17 were of postconceptual age greater than or equal to 37 weeks, 16 were postconceptual age less than or equal to 35 weeks without apnea and 10 were of postconceptual age less than or equal to 35 weeks with apnea. All infants were clinically stable. Two-way analysis of variance between groups showed no difference in the concentration of B-ELI in CSF or plasma, or in the CSF/plasma B ELI ratio. Concentrations of B-ELI in plasma were significantly higher in infants of postnatal age 1-3 weeks and greater than or equal to 4 weeks, than in infants of postnatal age less than 1 week. We conclude that, in nonstressed infants, there is no relationship between the concentration of B-ELI in CSF or plasma and a concurrent diagnosis of apnea of prematurity. Our data indicate that a significant developmental increase occurs in the plasma concentration of B-ELI after the first week of life. PMID- 2242712 TI - Desipramine effects on cocaine self-administration by rhesus monkeys. AB - The effects of desipramine treatment (0.56-10.0 mg/kg per day) on cocaine self administration were compared to saline treatment in five rhesus monkeys. Cocaine (0.050 or 0.100 mg/kg per inj) and food (1 g banana pellets) self-administration were maintained on an FR 4 (VR 16:S) reinforcement schedule. Desipramine (or an equal volume saline control solution) was infused over 1 h each day through the second lumen of an intravenous catheter. After 5 days of baseline saline treatment, seven doses of desipramine each were administered for 5 days in an ascending order. Cocaine self-administration increased (P less than 0.01) or remained equivalent to base-line levels in 4 of 5 subjects during the first 15 days of desipramine treatment (0.56 to 1.78 mg/kg per day). Three monkeys continued to self-administer cocaine equivalent to or significantly above base line levels (P less than 0.01) during days 16-30 of desipramine treatment (3.2 7.86 mg/kg per day). The highest desipramine dose (10 mg/kg per day) significantly suppressed cocaine self-administration in only one of these three monkeys (P less than 0.01). Desipramine treatment (3.2-10.0 mg/kg per day) suppressed cocaine self-administration (P less than 0.01) without a concomitant suppression of food-maintained responding in one of five subjects. A generalized suppression of both cocaine and food-maintained responding (P less than 0.01) during desipramine treatment occurred in one monkey that took the highest base line levels of cocaine (6.3 +/- 1.03 mg/kg per day). Food-maintained responding remained equivalent to or significantly above (P less than 0.01) base-line levels in four of five monkeys during desipramine treatment. A transient decrease in food self-administration at desipramine doses of 1.78-5.62 mg/kg per day occurred in one monkey (P less than 0.01). Thirty days of desipramine treatment at the highest doses (5.62, 7.86 and 10.0 mg/kg per day for 10 days each) also did not suppress cocaine self-administration in a monkey that took an average of 4 mg/kg per day of cocaine during saline base-line treatment. These primate data are concordant with the extant clinical literature on the inconsistent effects of desipramine treatment; i.e., both stimulation of cocaine use and inconsistent or incomplete attenuation of cocaine abuse during desipramine maintenance have been reported. PMID- 2242713 TI - Risk characteristics associated with chronic unemployment in methadone clients. AB - Relatively few methadone programs emphasize vocational skills training in their service delivery protocols. As a result, this study was conducted to determine the contribution of background demographic, vocational and clinical characteristics in differentiating chronically unemployed methadone clients from those regularly or intermittently employed over a 3-year period of time. Three hundred eighty heroin addicts, from five urban methadone treatment programs, participated in the study. Using the multiple logistic regression approach, nine variables were found to be significantly related to unemployment risk. PMID- 2242714 TI - Intravenous self-administration of 4-methylaminorex in primates. AB - The reinforcing effects of (+/-)-cis-2-Amino-4-methyl-5-phenyl-2-oxazoline (4 methylaminorex) were determined in two models of intravenous drug self administration in primates. In baboons, lever pressing was maintained under a fixed-ratio (FR) 80- or 160-schedule of intravenous cocaine delivery (0.32 mg/kg per injection). Each drug injection was followed by a 3-h time-out allowing a maximum of 8 injections per day. Vehicle or 4-methylaminorex doses were substituted for cocaine for a period of 15 or more days. One of the two 4 methylaminorex doses evaluated (0.32 mg/kg per injection) maintained self administration behavior above vehicle control levels in all four animals. This dose of 4-methylaminorex maintained cyclic patterns of self-injection behavior across days and produced signs of psychomotor stimulant toxicity. In rhesus monkeys, 4-methylaminorex (0.0003-0.1 mg/kg per injection) was made available to animals trained to self-administer cocaine (0.01 or 0.033 mg/kg per injection) under an FR 10 schedule of reinforcement during daily 1-h sessions. Each of the three monkeys self-administered at least two doses of 4-methylaminorex at rates exceeding those maintained by vehicle injections. Taken together with reports of recreational abuse of 4-methylaminorex, the present results indicate that this drug has a potential for abuse similar to that of other psychomotor stimulants. PMID- 2242715 TI - Demonstration of naturalistic methods for cocaine smoking by human volunteers. AB - Five, healthy, adult, male research volunteers participated in up to four daily laboratory sessions while residing on a Clinical Research Unit. Two subjects were tested twice. Fifty milligrams of cocaine base was smoked one, two or four times each session with a 14-min interval between doses. Two subjects smoked cocaine placed in 'smoke-free' cigarettes, while the remaining subjects smoked cocaine placed in a modified tobacco pipe. Significant and biologically relevant cocaine venous blood levels were engendered most consistently using the modified tobacco pipe. Large, transient increases in heart rate, blood pressure and self-reported 'stimulated' scores were observed during single dosing sessions. During multiple dose sessions, cardiovascular activity either increased, returning to near baseline levels between doses, or were sustained, while reported 'stimulated' scores peaked after the first dose and were lower following subsequent doses. Both cardiovascular and subjective effects were greater on the ascending limb than on the descending limb of the cocaine blood level curve suggesting acute tolerance. Although preliminary, these results demonstrate the usefulness of this relatively simple procedure requiring subjects to smoke in the manner they are accustomed, and suggest the importance of further research in this area. PMID- 2242716 TI - The use of flavor in cigarette substitutes. AB - Cigarette smokers identify flavor as an important factor in the pleasure derived from smoking and for their choice of cigarette brand. The issue of cigarette flavor has received a great deal of study by cigarette manufacturers but relatively little by academic investigators. The paucity of literature is particularly acute in terms of the importance of flavor in cigarette substitutes, which are used to help people to reduce or quit smoking. In the current study, five different types of flavors added to a plastic cigarette substitute were assessed in experienced smokers. There were two menthol-like flavors and three tobacco-like flavors. Two groups of smokers were tested: menthol smokers and "regular" (non-menthol) smokers. Both types of smokers liked the two menthol flavors significantly more than placebo and rated the menthol flavors and the cigarette flavor as significantly more satisfying than placebo. Craving was differentially reduced in the two groups of smokers. Menthol smokers showed a small reduction in craving with the placebo, with a significant enhancement of this reduction seen with the addition of the "EZ Quit" menthol flavor. PMID- 2242717 TI - Apolipoprotein distribution in plasma HDL subfractions in alcohol consumers. AB - Alcohol intake is known to increase plasma HDL subfractions and apo A levels. Few data are available, however, with regard to precise apoprotein composition of plasma lipoproteins in alcohol consumers. The aim of the present study was to examine the lipid and apoprotein distribution in plasma lipoproteins of subjects with different levels of alcohol intake. Thirty-six male regular drinkers were classified as social (n = 10, average daily consumption greater than or equal to 5 and less than or equal to 20 g), moderate (n = 11, average daily consumption greater than 20 g and less than 70 g) and heavy drinkers (n = 15, average daily consumption greater than or equal to 70 g). Reference data were obtained from 11 subjects, all lifelong abstainers. Lipoproteins were fractioned by sequential ultracentrifugation and apolipoprotein distribution in VLDL, HDL-2 and HDL-3 was determined by isoelectrofocusing in polyacrylamide-urea gel. HDL-2 cholesterol was significantly higher in heavy drinkers (P less than 0.005). A parallel trend for HDL-3 cholesterol was observed. In alcohol consumers HDL-2 particles were enriched in apos C, in particular apo C-II (P 0.005), displacing apo A-I. These data suggest that apolipoprotein distribution in the HDL-2 subfraction is influenced by alcohol intake even at the lowest level. PMID- 2242718 TI - Liver function tests in non-parenteral cocaine users. AB - To investigate the effect of cocaine on standard liver function tests (LFT), we studied 46 cocaine users with no history of parenteral drug use or homosexuality. LFT were similar in 21 users of cocaine only (Group A) and 25 users of cocaine and alcohol (Group B). Only three patients, two of whom were hepatitis B carriers, had an alanine aminotransferase level more than five units above normal limits. Group B patients were significantly more likely to complain of headaches, irritability, and loss of memory. We conclude that (1) non-parenteral cocaine use is rarely associated with significant LFT abnormalities and (2) alcohol may potentiate some adverse effects of cocaine. PMID- 2242719 TI - Using a drinking motivation scale to predict degrees of problematic drinking. AB - Much of the recent interest in the role of cognitive factors in decisions to drink has focused on alcohol beliefs and drinking motivations. In this study, male alcoholics in treatment, untreated problem drinkers and non-problem drinkers were studied using a variation of the Mulford and Miller Definitions of Alcohol Scale, which assesses personal-deficiency and social/celebratory reasons for drinking. The three groups of drinkers differed significantly on their mean level of endorsement of items comprising each drinking motivation subscale. The alcoholics scored highest on both personal-deficiency and social/celebratory reasons for drinking, followed by the problem drinkers and then non-problem drinkers. The problem drinkers and non-problem drinkers, relative to the alcoholics, rated their social/celebratory reasons for drinking stronger than their personal-deficiency reasons. A multiple discriminant analysis yielded a function which was moderately successful in classifying the alcoholics (70% correctly classified) and non-problem drinkers (67%). The problem drinkers were much more difficult to correctly classify (32% were classified as alcoholic, 49% as non-problem drinkers). The findings suggest that potentially important differences exist in drinkers' motivations to consume alcohol, motivations that vary as a function of problem drinking severity. These are results which might productively be used in assessment and treatment endeavors. PMID- 2242720 TI - "Experimenting" with drugs: a critical evaluation. AB - A group of adolescent drug "experimenters" as defined by the frequency of use (N = 496) were compared to non-users (N = 2417) and to "regular" users (N = 125) on a number of variables. These covered the patterns of use, attitudes to drug use, exposure to drugs and to drug use, and other behavioural correlates. Experimenting with drugs seems to indicate an unfavourable shift in adolescent behaviour. Experimenters were more likely to resemble regular users especially with respect to the behavioural correlates. In the light of the results observed, the various contexts in which the term "experimenting" is currently being used are examined with the conclusion that usage of the term remains to be ambiguous, over-inclusive, unjustified, and should be abandoned. PMID- 2242721 TI - Effect of ethanol on hepatic iron, copper, zinc and manganese contents in the male albino mouse. AB - Liver Fe and Cu contents (determined by atomic absorption spectrophotometry) were found to be higher in alcoholized male albino mice than in controls. Alcoholized animals killed at the 180th day of life also showed higher liver Fe and Cu contents than the alcoholized animals sacrificed at the 85th day of life. A significant correlation was established between liver Fe content and size of the pericentral hepatocytes and their nuclei. No differences between alcoholic and controls were obtained regarding liver Zn content, whereas Mn showed a clear tendency to be higher in the alcoholics. PMID- 2242722 TI - Habituation of skin conductance response in a methadone population. AB - By measurement of the habituation to the skin conductance response (SCR) no reduction of activation could be observed between stable patients in methadone maintenance therapy and healthy normal subjects, but significant differences were obtained between the well-performing group and poly-drug users treated with methadone. The findings are discussed within the context of previous research on outcome of methadone maintenance. Measurement of habituation to SCR is a useful instrument for detecting polydrug addicts in methadone maintenance programmes. PMID- 2242723 TI - The use of tobacco products among Nigerian adults: a general population survey. AB - This study was designed to investigate the incidence of cigarette smoking, cigar/pipe tobacco and snuff use in the Nigerian population. In a sample of 1271 adult heads of household (1137 males, 134 females) the overall prevalence of regular smoking was 22.6%. The proportions of regular cigar/pipe tobacco and snuff users were 17.9% and 9.6% respectively. Among cigarette smokers, 60.6% smoked at least half a pack a day, 11.2% at least one pack a day. Males smoked more than females. The poor, uneducated respondents smoked more than the relatively rich and educated. Smoking was more rampant in the third decade of life than in other age groups. Smokers had a higher incidence of health problems and both nonsmokers and heavy smokers were less aware of the risk of smoking than light smokers. In light of the above it is suggested that health education should be a major component of tobacco and health policy in Nigeria. PMID- 2242724 TI - Cultural differences in the perception of magazine alcohol advertisements by Israeli Jewish, Moslem, Druze and Christian high school students. AB - This article describes the Israeli part of an international comparative research project conducted simultaneously in 1988 also in Australia and in the U.S.A., in order to determine the attitudes of high school students from different nations and cultures toward alcohol advertising. The Israeli study used a set of 64 magazine alcohol advertisements from 10 countries and with the help of an open ended questionnaire examined differences and similarities in the perception of Israeli and foreign advertisements by Jewish, Moslem, Druze and Christian teenagers. Each response was coded twice. The first code indicated the general tone of the response and the second code indicated its theme. The article presents selected general results and conclusions. The results have implications for designing alcohol abuse education messages and can aid alcohol advertisers interested in responsible advertising to find advertising standards suitable to each culture. PMID- 2242725 TI - The role of alcohol-related problematic events in treatment entry. AB - This is an analysis of alcohol-related problematic events experienced by alcohol treatment clients in the year before treatment and the reporting of these events as major reasons for treatment entry. A probability sample of new intakes (N = 316) of the 8 contracted alcohol programs of a California county was interviewed. Data were collected on demographics, drinking patterns and a series of ten problematic events. Events (N = 982) are the unit of analysis. The analysis examines the events reported as major reasons for entering treatment. Logistic regression is used to investigate the socio-demographic and drinking variables associated with that reporting. Drinking driving, relapses and serious drinking episodes were reported as being major reasons for entering treatment a significant proportion of the times they occurred. Public drunkenness and non traffic accidents had significant proportions of individuals reporting them as not being major reasons for treatment when they occurred. Age, gender, ethnicity, marital status, employment and frequency of drunkenness were predictors of some types of events being major reasons, but there was no pattern across all events. The variables associated with experiencing an event were not the same as those which predicted the event would be reported a major reason for treatment. PMID- 2242727 TI - [The Automicrobic System (AMS)--a new test method for the classification and susceptibility testing of bovine mastitis streptococci]. AB - In the period of January 1987 to March 1988 15,800 quarter milk samples from cows of Lower Austrian problem herds were collected and 744 streptococci strains isolated. These 744 isolates were identified by means of the AUTO-MICROBIC-SYSTEM (AMS). As comparative methods the test system API 20 STREP as well as the comparison with the agar-diffusion test. Due to AMS 360 (=48.4%) of the 744 isolates examined could be identified as streptococci and referred to following species: 16 (=4.4%) Sc. agalactiae, 205 (=56.9%) Enterococci; 74 (=20.5%) Sc. uberis; 61 (=16.9%) Sc. of the viridans streptococci and 4 (=1.1%) Sc. pneumoniae. Both test systems AMS and API 20 STREP showed a coincidence of 91.6%. PMID- 2242726 TI - Target animal safety test of a dexamethasone-prednisolone combination in horses. AB - The target animal safety of a dexamethasone-prednisolone combination was studied on 12 horses divided into two groups of six each. One group of horses received the therapeutic dose of the combination (25 mg/animal dexamethasone pivalate and 75 mg/animal prednisolone) and the second group was given the threefold dose of it. The preparation was administered intravenously for 2 consecutive days. For assessment of safety a wide range of clinical, haematological, biochemical and urine variables were tested as laid down in the guidelines of the FDA. All horses treated by the therapeutic or the threefold therapeutic doses of the preparation remained in good health throughout the entire study. No signs of clinical abnormalities occurred in either group. The physiological variables tested failed to reveal any significant alteration as a consequence of the medications. Of the haematological and biochemical parameters leucocyte, neutrophil, eosinophil and lymphocyte counts, aspartate aminotransferase activity, glucose, phosphor, total and conjugated bilirubin and creatinine concentrations were significantly affected in both groups. In some animals a transient glucosuria occurred. From the direction and magnitude of these changes it was concluded that they did not reflect any toxic actions of the preparation. Nevertheless, the combination is to be administered only with exact therapeutic indications and the uncontrolled misuse of it must be avoided. PMID- 2242728 TI - [The effect of selected output parameters on the flushing results of MOET (Multiple Ovulation and Embryo Transfer)]. AB - Superovulation responses from 299 Hessian donors were used to analyse the influence of selected traits and ovulation-parameters. The effects of the age of life were similar to those of other authors. Fat yield (phenotypic) showed a small positive influence on the number of collected embryos. Genetic value of the sire had no effect and using sperm of one or two bulls made no difference. A prediction of an individual MOET-response by a selected parameter is not possible. PMID- 2242729 TI - [Fertility controls as the measure of herd fertility of dairy stock]. AB - Hormonal analyses have been conducted along with intensive clinical following-up of the animals of three dairy herds in the area of Thessaloniki/Greece for a two year period. The data and progesterone profiles collected by means of milk progesterone assay (EIA) contribute considerably towards confirming and/or correcting clinical diagnoses. The clinical findings and the fertility parameters illustrate the considerable burden of fertility problems present in the dairy herds. The authors assume that faults in nutrition constitute the cause of silent heat and the problems derived from it. Faulty management is mainly associated with difficulties in oestrus diagnoses owing to disorders of fertility, failure to keep precise fertility data and the effects of inconsistent servicing of the cows on the part of the state inseminators. PMID- 2242730 TI - [The effect of monensin, tiamulin and the simultaneous administration of both substances on the microsomal mixed function oxidases and on the peroxide formation in broilers]. AB - The influence of Monensin, Tiamulin and the simultaneous administration of the two substances on the microsomal, mixed function oxidases was studied on cockerels. Monensin was seen to cause a slight depression in the amount of cytochrome P-450 and cytochrome b5 as well as in the activities of aniline-p hydroxylase, p-nitrophenol-hydroxylase and p-nitroanisole-O-demethylase. Tiamulin induced a moderate increase in the amount of cytochrome P-450 and in the activities of aniline-p-hydroxylase, p-nitrophenol-hydroxylase and aminopyrine-N demethylase. The combined administration of monensin and tiamulin resulted in marked induction of the microsomal enzymes; the amount of cytochrome P-450 reduced by metyrapone or carbon monoxide increased 2.5 or 2-times, respectively, and the activities of the tested microsomal hydroxylases and demethylases showed also an expressed increase. At the same time the formation of lipid peroxides also markedly increased and the GSH concentration was reduced. In conclusion, the results of the investigations indicate that the simultaneous application of monensin and tiamulin cause a marked induction of the drug-metabolizing microsomal enzymes and a significant increase in the lipid peroxide formation. PMID- 2242731 TI - [Morphologic changes in the intestine of swine after infection with verotoxin producing Escherichia coli]. AB - Spontaneous morphologic lesions are described in 12 of 66 pigs submitted for necropsy. All 12 pigs were culture positive for Verotoxin-producing E. coli (VTEC). 10 of them were weaned pigs, one a suckling piglet and one a fattening hog. In 6 cases E. coli serovar 0139:H1 and in one case each the serovars 0139:H40; 0138:H-; 0125ac:H27 and 0154:H- were isolated. From the fecal samples of 2 animals E. coli ONT (O-group non typable):H- were cultured. Macroscopically there were cyanosis, edema of the eye lids, catarrhal enteritis and/or colitis as well as edema of the mesentery, swelling of the mesenteric lymph nodes and congestion of the lung to varying degrees. Histopathologic examination of 5 animals was carried out. In 3 animals atrophy and edema of the villi in the jejunum and ileum were discovered. In one animal an additional infection with corona virus was confirmed electron microscopically. Furthermore there was disseminated necrosis of lymphocytes in Peyer's patches of the small intestine and in secondary follicles of the mesenteric lymph nodes. In one of the animals a hemorrhagic-necrotising ileitis, occurred characterized by necrosis of villi and thrombosis of blood vessels in the mucosa. The highest number of VTEC with seven out of twelve animals was found in weaned pigs in association with the E. coli serovar 0139. PMID- 2242732 TI - [The effect of the anesthetic Tilest in swine]. AB - The clinical signs and effects on the cardio-respiratory system of Tilest were checked out in weaners. The intramuscular injection of 10 mg/kg BW Tilest caused a rapid immobilisation on an average duration of 33.7 +/- 15 minutes. The muscle relaxation was generally good. Analgesia could not obtained. Heart- and respiratory-rates increased during lateral recumbency. Blood pressure decreased initially. The influence on the arterial blood pH-value and the blood gases are insignificant. In connection with trials to get up the lactate value and the body temperature increased. The CK- and ASAT-activities increased 2 to 6 hours after injection with a wide individual variation. During recovery the pigs were excited and salivated. PMID- 2242733 TI - [Atrophic rhinitis in swine and other animal species]. AB - Evidence that cattle, goats and rabbits may suffer from natural diseases equivalent to porcine atrophic rhinitis is presented. Etiology and course of the progressive (enzootic) and non-progressive (sporadic) forms of atrophic rhinitis in pigs are discussed and compared with known data about similar diseases in other animals. It seems that atrophic rhinitis caused by toxigenic strains of Pasteurella multocida may be a disease of different animal species. PMID- 2242734 TI - [Wedge-shaped vertebral formation as the cause of leg weakness syndrome in swine- a case report]. AB - We report about two cases of hemivertebrae in pigs. The malformations appeared in the T2/3, respectively in the T10. One case showed clinical apparent signs, namely ataxia and leg weakness. The productivity of the affected pig was reduced. Both cases are of unclear genesis. A hereditary predisposition could not be proved. PMID- 2242735 TI - [Animal nutrition for veterinarians--recent cases of "cramping colic" in horses after feeding of spoiled oats]. PMID- 2242736 TI - [Illustrated report: forestomach actinomycosis with partial obstruction of the dome of the rumen opening in a breeding animal]. PMID- 2242737 TI - Inflammatory fibroid polyp of the stomach. AB - Among 3,200 polyps of the stomach, we diagnosed inflammatory fibroid polyp in 143 patients (4.5%). The average age of the patients was 63.6 years (women) and 63.9 years (men), the sex ratio being 1.6 women to 1.0 men. In 77.6% of the cases, the polyp was located within the antrum, in 9.8% in the angular notch region, 1.4% in the pylorus, and 0.7% each in the fundus and cardia. The characteristic histological feature of these lesions is an eosinophil-containing, loosely structured fibrous tissue comprising an onion-skin-like arrangement of reticular fibers with spindle-shaped nuclei localized in the submucosa and the base of the mucosa. The polypous bulging mucosa was eroded in 26.8% and ulcerated in 3.5% of the cases. A comparison of the 147 cases collected from the literature with our own 143 cases revealed no differences. The rarity of inflammatory fibroid polyps in the stomach, their predominant location in the antrum, the age distribution and the observation that, after removal, these lesions do not recur, all go to suggest that the lesion is a reactive process (allergic or foreign body reaction), possibly a residual state following infestation by a parasite larva. PMID- 2242738 TI - Endoscopic examination for fistula. AB - In 15 postoperative fistula cases, we performed endoscopic examination (fistuloscopy) and studied the clinical significance. The inside of the fistula was easily observed after irrigation with physiological saline. The drain was extubated in 6 cases in which cavities without abscesses were recognized. In a case of pancreatic fistula, the fistula was temporarily closed using fibrin glue. Re-operation was performed in a case in which recurrence of cancer was recognized by biopsy. On the other hand, in 9 cases in which cavities with abscesses were recognized, foreign bodies, such as suture threads, which were sources of infections were removed. Moreover, the drain was removed to the effective site, and the fistula then irrigated repeatedly. Consequently, with the exception of a death due to cancer and a case complicated by osteomyelitis, the fistula was closed in all cases. Fistuloscopy is a safe and easy technique. In addition, the method, which is less stressful for the patient, is considered to be effective for the examination and treatment of fistulas. PMID- 2242739 TI - Postoperative external and internal biliary fistulas, unassociated with distal bile duct obstruction: endoscopic treatment. AB - Endoscopic drainage was applied in 14 patients with either external or internal (bile ascites) postoperative biliary fistulas. Endoscopic sphincterotomy and/or insertion of a nasobiliary tube or an endoprosthesis was found to be a safe and effective treatment, achieving closure of fistula in all patients. PMID- 2242740 TI - Comparison of a new colon lavage solution (Iso-Giuliani) with a standard preparation for colonoscopy: a randomized study. AB - Iso-Giuliani is a new improved-taste isoosmotic PEG-electrolyte solution for colon cleansing. In a randomized study, we have compared the effectiveness, tolerance and patient acceptance of 3 dosage volumes of this solution with a standard preparation in 191 patients undergoing colonoscopy. Iso-Giuliani 3 1, and 4 1 proved better colonic preparations as compared with the standard preparation (P less than 0.01). However Iso-Giuliani, 21 was sufficient for satisfactory cleansing, especially in the rectosigmoid. Patients in the standard preparation group experienced more cramps than did those in Iso-Giuliani groups. Patient acceptance was significantly better for Iso-Giuliani than for the standard preparation. The ingestion of Iso-Giuliani represents a safe, effective and well-accepted method of colon cleansing, and is our elective method of preparation for colonoscopy. PMID- 2242741 TI - An investigation of an infrared ray electronic endoscope with a laser diode light source. AB - An infrared ray electronic video-endoscope with a laser diode light source was used to obtain information on the submucosal area. As contrast medium we employed indocyanine green, which has a light absorption peak in the infrared range. The wavelength of the laser diode was set to 810 nm as suggested by the results of the spectrophotometric study on the reflected light at fingertips after injection of ICG (3 mg/kg). Using this system we inspected the stomach under visible light and then continuously under infrared light before and after intravenous injection of ICG (2 mg/kg). A dendritic figure with fine ramifications emerged in the early stage after intravenous injection of indocyanine green, which was not seen under visible light. These features of the figure visualized by the infrared endoscope suggest that they have a close relationship with blood vessels and blood circulation beneath the mucosal surface. This infrared electronic endoscope system provides submucosal information more readily and at a lower cost than ever before, and also the infrared lighting method of this system could be applied to almost all available electronic endoscopes by modulating infrared cutting filters, so it could become a valuable clinical tool. PMID- 2242742 TI - A new technique in endoscopic ultrasonography of the upper gastrointestinal tract. AB - Endoscopic ultrasonography (EUS) of the upper GI tract was unsuccessful in 42 out of 274 patients (15%) due to inaccurate guidance of the probe to small, shallow lesions, or to difficulty in clearly demonstrating the surrounding layer structure and boundary of the lesion. We applied the saline injection technique in these 42 patients. Saline was injected into the submucosal layer of the esophagogastric wall. The ultrasonographic image of adjacent saline accurately guided the probe to the lesion. Injected saline enabled the mucosal layer to be distinguished from the muscularis propria surrounding the lesion and provided clear ultrasonographic imaging of the boundary between the lesion and the surrounding layer structure. This new method was found to be effective in 38 out of 42 patients in whom EUS was unsuccessful. A study comparing the depth of tumor invasion diagnosed by the saline injection technique with histological findings obtained in 12 cases showed good correlation. These results indicate that the saline injection technique would seem to be very useful as an adjuvant to conventional EUS. PMID- 2242743 TI - A new endoscopic method for managing food impaction in the esophagus. AB - Previously described methods for dealing with acute food impaction in the esophagus are not uniformly efficacious, are cumbersome, and often prove dangerous. This paper describes a new technique using an endoscope which is modified such that the endoscope itself becomes a direct-vision suction device. We have successfully used the technique in seven patients with meat bolus impaction in the esophagus. The method proved quick and safe, and no complications occurred. After relieving the impaction an adequate diagnostic examination was done in all patients. In four patients with a predisposing peptic stricture and one with Schatzki's ring, treatment of the lesion was possible during the same endoscopic session. PMID- 2242744 TI - Electrohydraulic lithotripsy of complicated choledocholithiasis. PMID- 2242745 TI - Fatal air embolism following endoscopy of a hepatic portoenterostomy. AB - The case reported is that of a 10-year-old girl born with congenital biliary atresia who had undergone a Kasai procedure in the first year of life. She presented with ascending cholangitis, and investigations revealed a stricture of her portoenterostomy with an intrahepatic stone above the stricture. At laparotomy there were numerous adhesions and dilated varices, so the descending loop of the Kasai was exteriorized to enable a subsequent percutaneous endoscopic manipulation of the stone. During manipulation of the stricture via a pediatric endoscope in the jejunal loop the patient collapsed and died. Post mortem revealed a massive air embolism and varices of the jejunal loop. PMID- 2242746 TI - Rectal pseudotumor due to Chlamydia trachomatis in a male homosexual. AB - Chlamydia trachomatis causes a wide spectrum of human genital infections including lymphogranuloma venereum. We describe an unusual case of Chlamydia trachomatis proctitis in a homosexual man presenting with a large, solid tumor in the distal rectum, which was treated successfully by long-term oral doxycycline therapy. PMID- 2242747 TI - Iatrogenic lesions of surgically treated papilla of Vater. PMID- 2242748 TI - Not a way to do esophageal bougienage. PMID- 2242749 TI - Biliary endoprosthesis in the treatment of large common bile duct stones. PMID- 2242750 TI - The bee: an unusual gastric foreign body. PMID- 2242751 TI - The relation between cycling time to exhaustion and anaerobic threshold. AB - This study investigated whether the anaerobic threshold (AnT) could be used to predict prolonged work capacity measured as cycling time to exhaustion (= endurance time) and which factors, in addition to relative exercise intensity, could explain variation in endurance time. Theoretical exercise intensities corresponding to certain endurance times were also calculated. The hyperbolic and exponential functions between cycling time and relative work rate (WR[%]), as well as between cycling time and relative oxygen uptake (VO2[%]) were fitted to the pooled data (n = 45) of 17 subjects. The WR(%) and VO2(%) were expressed as a percentage of the subject's own AnT- and maximum-values. At WR corresponding to AnT (i.e., 70% of WRmax) an average subject could cycle 60 min according to both AnT- or maximum-related exponential function. When prediction was done for an endurance time of 4 h, the AnT-related exponential function gave 2.9%-units (= 11 W or approximately 0.15 O2 l.min-1) lower intensity level (51% of WRmax) than the maximum-related function (54% of WRmax). The WR(%) alone explained 54% and 70% of the variation in endurance time of the AnT-related and maximum-related exponential functions, respectively. Muscle fibre composition and initial blood lactate or relative muscle glycogen depletion (change in muscle glycogen as percentage) increased significantly the explanatory power of these models. The differences between the observed and expected exercise times correlated with blood lactate accumulation (r = -0.42; p less than 0.01), muscle fibre composition (r = 0.33; p less than 0.05) and relative muscle glycogen depletion (r = 0.67; p less than 0.01). It was concluded that the capacity for prolonged work measured as cycling time to exhaustion can be estimated by AnT-related power output, and that the exponential function model is the most suitable. Prediction power of the model can be improved by multiple regressions including muscle fibre composition, initial blood lactate level and relative muscle glycogen depletion. PMID- 2242752 TI - Fifth World Congress of Nuclear Medicine and Biology. August 26-31, 1990, Montreal, Quebec, Canada. Abstracts. PMID- 2242753 TI - Analysis of the immune-encodrine feedback loop in the avian system and its alteration in chickens with spontaneous autoimmune thyroiditis. AB - In both mammals and chickens, immunization with exogenous antigens results in a surge of serum glucocorticoid hormone levels concomitant with the antibody response. This effect is mediated by glucocorticoid-increasing factors (GIF) produced by cells of the immune system. In the avian system, GIF appear to act via the hypothalamo-pituitary axis and not directly on the adrenal gland. Interleukin 1 is the main active substance responsible for GIF activity, as shown by molecular sieve and immunoaffinity chromatography studies. In contrast to data from mammals, we found no evidence that interleukin 2 elevates chicken corticosterone. Obese strain chickens with spontaneous Hashimoto-like autoimmune thyroiditis are deficient in their in vivo GIF response. Because no differences were found between autoimmune and healthy chickens in the corticosterone response of the adrenal gland after ACTH administration, and since autoimmune animals are able to react normally to immobilization stress, it is assumed that this deficiency is due to a specific defect rather than a general disturbance in the endocrine system. PMID- 2242754 TI - In vitro human cytotoxic T cell responses against influenza A virus can be induced and selected by synthetic peptides. AB - Studies on human anti-influenza cytolytic activities have demonstrated that cytotoxic T lymphocytes (CTL) from HLA-B37 individuals react preferentially with the peptide corresponding to residues 335-349 of the nucleoprotein, whereas CTL from HLA-A2 donors recognize peptide 57-68 from the viral matrix as a dominant epitope. We studied the secondary CTL response, obtained from peripheral blood mononuclear cells, of an HLA-A2+,B37+ individual stimulated either by infectious virus or by synthetic peptides. Only an HLA-B37-restricted response was detected after stimulation by the whole virus, showing an immunodominance of this activity over that restricted by HLA-A2. Moreover, human cytotoxic cell lines were successfully obtained after stimulation of peripheral blood mononuclear cells with synthetic peptides. Under these conditions, it was possible to selectively reveal the existence of an HLA-A2-restricted activity directed against the matrix peptide. These results demonstrate that, at least in vitro, it is possible to stimulate a latent repertoire by using synthetic peptides. Nevertheless, we could not induce a response against the matrix or the nucleoprotein peptides in HLA-A2- or B37- individuals, suggesting that a finer selection of synthetic peptides would be necessary for their possible utilization to induce CTL during vaccination. PMID- 2242755 TI - The influence of S17 stromal cells and interleukin 7 on B cell development. AB - A clonal assay was used to study different stimuli involved in the progression of fetal liver B cell precursors to mature B lymphocytes. In this report we replaced fetal liver heterogenous feeder cells by a recombinant growth factor, interleukin 7 (IL 7), and a clonal stromal cell line, S17. Under those conditions we could clone 1 in 10 B220+ B cell precursors from fetal liver and the cells could differentiate to a mitogen-responsive, immunoglobulin-secreting stage. We found that IL 7 stimulates proliferation of B220+ precursors but is not sufficient to support maturation of those precursors to a stage of mitogen responsiveness. We show further that the cell line S17 does not produce IL 7 at functionally detectable level but provides support for B cell maturation. We conclude that this cell line supplies an exogenous stimulus required by B cell precursors to become mature lymphocytes. We describe therefore two stages in pre-B cell development: (a) IL 7-dependent proliferation and (b) S17-dependent maturation to mitogen reactivity. Further studies demonstrate that S17 has a profound effect on B cells by increasing the clonal efficiency of lipopolysaccharide-responsive cells to nearly 1:1 B cell in the spleen of adult C57BL/6 mice. PMID- 2242756 TI - A new surface antigen on intraepithelial lymphocytes in the intestine. AB - A new surface molecule has been discovered on mouse intestinal intraepithelial lymphocytes (IEL) using a rat anti-mouse IEL monoclonal antibody, M290. It was expressed at high levels on nearly all IEL and on a majority of T cells in the gut lamina propria. M290 stained, with lower intensity, a small minority of T cells in other lymphoid tissues. Expression was biased towards the CD8+ subset. Stimulation of peripheral T cells with mitogens did not induce expression of the new antigen but addition of transforming growth factor beta to stimulated T cells had a marked inductive effect. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of IEL surface components precipitated with M290 showed principal bands at 135, 120, 28 and 24 kDa (reduced) and 135, 100, 24 and 21 kDa (nonreduced). Precipitation with antibodies to integrin subunits showed that the new molecular complex was not a member of the beta 1, beta 2, or beta 3 integrin families although all of these were represented on IEL. A 13-amino acid N terminal sequence obtained from the 120-kDa beta subunit of the antigen prepared from an M290+ T hybridoma (MTC-1) did not show homology with integrins. Pulse chase studies using MTC-1 cells showed that the 135-kDa alpha subunit was derived from a 147-kDa precursor. The function of this new molecular complex is not yet known. PMID- 2242757 TI - Glycosylation of IgG, immune complexes and IgG subclasses in the MRL-lpr/lpr mouse model of rheumatoid arthritis. AB - The MRL-lpr/lpr (MRL/lpr) mouse spontaneously develops a disease syndrome which, in many respects, is similar to human rheumatoid arthritis. These mice developed joint inflammation, circulating rheumatoid factors and immune complexes. We now show that the parallel with human disease extends to a glycosylation defect which is observed on IgG from rheumatoid arthritis patients. Using the lectins ricin and Bandeiraea simplicifolia II we have found that terminal N-acetylglucosamine is clearly raised in MRL/lpr IgG. Increased exposure of galactose was also detected, indicating that a second glycosylation site must be present on these molecules. Polyethylene glycol-precipitated IgG complexes bound significantly more of each lectin than did free IgG, indicating that the changes in glycosylation were associated with complex formation. The sugar abnormality was most marked in the IgG2a/IgG3 fraction from protein A IgG subclass chromatography. Our results suggest that the IgG glycosylation defect seen in rheumatoid arthritis is apparent in the MRL/lpr mouse and may contribute, through complex formation, to the pathological processes in the rheumatoid syndrome. PMID- 2242758 TI - Characterization of an IgA receptor from group B streptococci: specificity for serum IgA. AB - Some strains of group B streptococci express a cell surface protein which binds IgA. This report describes some properties of such an IgA receptor and compares it with a previously described IgA receptor from group A streptococci. The group B receptor was released in an almost pure form from bacteria incubated at elevated pH, and could be isolated by IgA-Sepharose affinity chromatography. The sequence of the N-terminal 19 amino acid residues was unique. The receptor preferentially binds IgA of human origin, as shown in immunoblotting experiments with purified IgA from nine different species. The affinity constant of the purified receptor for serum IgA was determined to be 3.5 x 10(8) M-1, but for secretory IgA it was too low to allow determination. This result indicates that secretory component and/or J chain interferes with the binding of IgA to this type of bacterial receptor, which may be one of the physiological functions of these polypeptides. A reduction in affinity was also observed for another complexed form of IgA, alpha 1-microglobulin-IgA. The group B receptor is antigenically unrelated to the IgA receptor from group A streptococci (protein Arp), but competitive inhibition experiments indicate that they bind to the same region in IgA. The implications of these findings, and the biological role of bacterial IgA receptors, are discussed. PMID- 2242759 TI - Age-related decrement in cytotoxic T lymphocyte (CTL) activity is associated with decreased levels of mRNA encoded by two CTL-associated serine esterase genes and the perforin gene in mice. AB - The age-related decline in cytotoxic T lymphocyte (CTL) activity has been recognized for many years. Age-related alterations in several immunologic events have been suggested to be partly or completely responsible for this decline. We had previously demonstrated (Bloom et al., Cell. Immunol. 1988. 144: 440) in mice that a deterioration in the lytic mechanism may be at least in part responsible for the decline in CTL activity. We now report that this decline correlates with an age-related decrease in serine esterase activity released into the supernatant medium in the process of generating CTL. Northern analyses were then used to examine the effect of age on expression of genes encoding for perforin and two CTL-associated serine esterases. The products of all three of these genes have all been postulated to play roles in CTL-mediated lysis. We show that the expression of all three of these genes appears to decline with age in the process of generating allogeneic CTL. These alterations in gene expression correlated both with diminished cytolytic and released esterase activities generated by mixed leukocyte culture in spleen cells of old mice compared to young. The age related decline in gene expression could not be attributed to shifts in T cell subsets, but CD8+ cells generated by allogeneic stimulation of nylon wool-passed spleen cells from old mice expressed significantly less cytolytic activity than those from young. This report is the first demonstration of an age-related decrease in expression of a functionally related group of genes. In addition, these findings are compatible with the suggested roles for perforin and serine esterase release in CTL-mediated target cell lysis. PMID- 2242760 TI - Functional characterization of the antibody-mediated protection against blood stages of Plasmodium falciparum in the monkey Saimiri sciureus. AB - The squirrel monkey Saimiri sciureus is one of the World Health Organization recommended experimental models of Plasmodium falciparum blood stage infection. Anti-malaria antibodies developed by this host after a drug-controlled infection play an important part in the acquired protection against the P. falciparum blood stages. Furthermore, the use of two anti-Saimiri immunoglobulin (Ig) monoclonal antibodies (mAb) has permitted the differentiation between protective (mAb 3A2/G6) and non-protective (mAb 3E4/H8) antibodies, as shown by transfer experiments to recipient monkeys infected with blood stage parasites. In the present study we have established that protection conferred by the 3A2/G6+ protective Ig preparation is strictly associated with an in vitro opsonic activity. Such an opsonic activity is not detectable in the 3E4/H8+ non protective Ig population. In addition, results indicate that the 3E4/H8+ non protective Ig population competes with protective opsonic 3A2/G6+ Ig antibodies when co-incubated with parasitized red blood cells. Thus, it follows that protection can be directly correlated to the quantitative and qualitative fluctuation of the two Ig populations. When challenged with 1 x 10(8) P. falciparum-infected Saimiri red blood cells parasitemia occurred in 5 out of 12 Saimiri who were lacking detectable 3A2/G6+ opsonic antibodies in their sera. By employing antibodies against the human Fc receptor for IgG (Fc gamma R) in an in vitro phagocytic assay, we have been able to show that the principal receptor is Fc gamma RIII. Finally, we also show that in contrast to the situation in man, this receptor is present on circulating monocytes. These findings could lead to a different strategy in designing malaria vaccine candidates and also allow the possibility of predicting the outcome of immunization trials in Saimiri monkeys. PMID- 2242762 TI - Leukocyte function-associated antigen 1 (LFA-1) is a signaling molecule for cytoskeletal changes in a human T cell line. AB - The HuT 78/2 clone is a human T cell clone which has an activated phenotype. When this line was stimulated with immobilized antibody to LFA-1, the majority of cells developed dendritic processes. These processes were demonstrated to contain cytoskeletal elements including microtubules and intermediate filaments. Phorbol myristate acetate synergized with and prolonged this effect. Thus, the LFA-1 molecule may function as a signaling molecule for cytoskeletal reorganization in a human T cell clone. PMID- 2242761 TI - Generation of hen egg lysozyme-specific and major histocompatibility complex class I-restricted cytolytic T lymphocytes: recognition of cytosolic and secreted antigen expressed by transfected cells. AB - Syngeneic cells exogenously supplied with hen egg lysozyme (HEL) or endogenously synthesizing HEL were used as antigen-presenting cells to induce major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTL). Immunization of C57BL/6 mice followed by repeated stimulation of their splenocytes in vitro with trypsinized HEL peptides led to the generation of CTL lines specific for trypsinized HEL peptides and restricted by H-2K. Immunization of C3H mice with a mixture of soluble native HEL and irradiated syngeneic spleen cells followed by in vitro stimulation of immune spleen cells with soluble HEL could in a few cases result in HEL-specific CTL able to kill syngeneic transfectant L cells secreting HEL (HELs) or expressing cytosol-targeted HEL (HELc). The use of HELs or HELc transfectant L cells as in vivo and in vitro immunogens was a potent way for eliciting HEL-specific polyclonal CTL. These CTL and two CD8+ clones were found to be H-2K restricted and specific for the 1-17 N terminal HEL peptide. In addition, the anti-HEL CTL could also exhibit a significant cross-reactivity against unsensitized and HEL-untransfected targets expressing the K restriction element. This cross-reactivity was likely due to recognition of unidentified HEL mimicking peptides (self-derived?) presented by the MHC class I (H-2K or H-2K) molecule used as the restriction element for the specific recognition of HEL. The CTL raised after immunization with HELs or HELc transfectant cells were found to recognize both the HELs and HELc transfectant cells even though HEL was not detected in the latter after a 2- or 5-min radiolabeling pulse. Recognition of both HELs and HELc transfectant cells by a given CTL clone suggests that HEL subjected to two separate processing pathways, each depending on the initial subcellular localization, can ensure the generation of similar MHC class I peptide complexes. PMID- 2242763 TI - [Methodology for research on toxicity and its prediction]. PMID- 2242764 TI - [Characteristics of F344 rats in a stand-point of naturally occurring neoplastic and non-neoplastic lesions]. PMID- 2242765 TI - [Selective medium for Corynebacterium kutscheri and localization of the organism in mice and rats]. AB - A new selective medium for isolation of Corynebacterium kutscheri (CK) from animals suffering subclinical infection was made by adding furazolidone, nalidixic acid and corimycin to the heart infusion agar base, this being named FNC agar. The FNC agar inhibited the growth of gram-negative rods, Pseudomonas aeruginosa, Proteus sp. and gram-positive cocci but did not affect the growth of CK. When this medium was used to isolate CK from the oral cavity and cecal contents of mice and rats, two of 6 conventional mouse colonies and three of 8 conventional rat colonies were found to be infected, with isolation of the organism from 19 mice and 12 rats in total. The animals showed neither clinical signs nor lesions, but the antibody was positive in 11 mice and 10 rats. In mice and rats inoculated orally with 4 x 10(8) and 1 x 10(9) organisms, respectively, CK was isolated for 20 weeks post-inoculation by use FNC agar. The isolation rate of the organism was the highest in the oral cavities of both inoculated mice and rats, and also in the submaxillary lymph nodes of the inoculated rats. The organism was also recovered from the cecal contents of more than half of the inoculated mice and rats. Thus, it was considered that FNC agar was useful in isolating CK from the oral cavity and cecal contents of mice and rats with subclinical infection of the organism. PMID- 2242766 TI - Theiler's murine encephalomyelitis virus--characterization of newly isolated viruses from Japanese mouse colonies. AB - The hemagglutinating-inhibition (HI) test was used to detect antibodies for Theiler's murine encephalomyelitis virus (TMEV), and the virus was isolated from sero-positive mice derived from colonies in Japan. HI antibody was detected in conventional mice (38.7%; 137/354) at titers ranging from 1:8 to 1:512, but it not in SPF mice (0/90). To isolate the virus, weanling mice inoculated intracerebrally with samples obtained from sero-positive mice were sacrificed and 10% brain homogenates were subcultured. New isolates designated as YOC and AB strains were obtained, and their physicochemical and biological properties were characterized. The results indicated that the new isolates were similar to Theiler's original (TO) strain according to the following observations of persistent paralysis of the hind limbs, resistance to ether treatment, a particles size of 10 approximately 50 nm in diameter, stability at pH 3, a density of 1.35 g/cm3 and three major and one minor viral proteins, (VPO; 38 Kd, VP 1; 33 Kd, VP2; 32Kd, VP3; 25 Kd). Immunoblotting analysis also showed that VP 2 of YOC and encephalomyocarditis virus of the Cardiovirus group, reacted strongly with the antisera against the viruses as well as with the GDVII strain. These results suggest that TMEV infection does exist in conventional mouse colonies in Japan, and that these viruses resemble the TO strain of TMEV. PMID- 2242767 TI - Determination of an antigen suitable for enzyme-linked immunosorbent assay of the antibody to Bordetella bronchiseptica in guinea pigs. AB - To establish an enzyme-linked immunosorbent assay (ELISA) technique for the serological diagnosis of infections caused by Bordetella bronchiseptica (B. bronchiseptica) in guinea pigs, the authors recently assessed the usefulness of three antigen preparations derived from the bacterial cell components: sonication antigen (S-Ag), cell surface antigen (C-Ag) and lipopolysaccharide antigen (L Ag). The use of S-Ag for ELISA resulted in the most sensitive detection of the antibody to B. bronchiseptica from guinea pig sera immunized with killed bacteria and sera derived from naturally infected guinea pigs. Like C-Ag, S-Ag was highly specific, showing no cross-reactivity with Pasteurella multocida. Assessment of antibody formations in animals with experimentally induced infection using the three antigen preparations revealed that the antibody to S-Ag was formed earlier than antibodies to the other two antigen preparations following growth of the bacterium in the lungs. These results indicate that ELISA with S-Ag as an antigen is a useful tool for the serological diagnosis of infection by B. bronchiseptica. PMID- 2242768 TI - Arterial pressure and its variability in conscious rabbits at different ages. AB - Mean level and its variability of mean arterial pressure (MAP) were studied in 25 unanesthetized rabbits aged 6, 12, 18, 24 and 30 months. They were selected from the same large colony and bred with an ordinary rabbit food under a given environmental conditions. MAP in the aortic arch was continuously monitored with a catheter-transducer system for 3 hrs. Mean (M) and variance (V) of MAP for 3 hrs were not significantly altered with aging (p greater than 0.05, Kruskal Wallis' multi-sample test). Intra-animal variations of the M and SD were small. Most of histograms of MAP for 3 hrs shows an exaggerated mode at any age. Distribution pattern of the histogram was not specific to age. These suggest that responsiveness of the baroreflex system should not be affected by aging from 6 to 30 months. PMID- 2242769 TI - [Visual function of cynomolgus monkeys with macula degeneration and peripheral retinal degeneration]. AB - Using the simplified method for judging visual function of the cynomolgus monkey that was established by the present authors (Suzuki et al., 1988), forty-four cynomolgus monkeys with normal ophthalmoscopic findings, eleven monkeys with macula degeneration and thirteen monkeys with peripheral retinal degeneration were examined for their visual function. It was demonstrated that the monkeys with macula degeneration were inferior in their visual function to the monkeys with normal fundus. In addition, the degree of visual function varied with the degree of macula degeneration. The monkeys with peripheral retinal degeneration showed about the same degree in their visual function as the monkeys with normal fundus. PMID- 2242771 TI - Effects of mandibular gland ectomy and environmental temperature of dams on eyelid opening and body weight of pups in mice. AB - Effects of the mandibular gland ectomy and environmental temperature to pups in Jcl: ICR mice were studied. In normal environmental animal room (A room; Tem. 23 +/- 2 degrees C, R. H. 50 +/- 10%), the mammary gland weights of lactating mothers and the body weights of pups in sialoadenectomized groups were slightly smaller than that of control groups during lactating period, whereas the eyelid opening of pups was not different between both groups and all pups exhibited complete eyelid opening on 14th day after birth. On the other hand, in cold environmental animal room (B room; Tem. 15 +/- 2 degrees C, R. H. 60 +/- 20%), the mammary gland weights of lactating mothers and the body weights of pups in sialoadenectomized groups were smaller than that of sialoadenectomized groups in A room and the eyelid opening of pups was considerably delayed when compared with that of control groups. The pups exhibited complete eyelid opening at 16th day after birth. These results were caused by mandibular gland ectomy and considered to be easily influenced by environmental conditions. PMID- 2242770 TI - [Spontaneous bone marrow granulomas in rats--effect of ovariectomy on granulomas formation]. AB - Spontaneous granulomas developed frequently in the bone marrow of Slc: Wistar female rats over 19 weeks of age, whereas none did in JCL: SD and Slc: SD rats of either sex. These granulomas were composed histologically of epithelioid cells and macrophages clustered mostly in the center and lymphocytes and plasma cells located in the periphery, and they contained neither microorganisms nor foreign bodies. Ovariectomy of Slc: Wistar rats at 6 weeks of age resulted in a significant decrease in the incidence and size of bone marrow granulomas at 20 and 24 weeks of age. It is concluded that two factors, the strain of rats and female sex hormone, contribute to the pathogenesis of bone marrow granulomas--the former as a hereditary disposition and the latter as a promoter. PMID- 2242772 TI - [Method of dissecting of ovarian bursal membranes using a bipolar coagulator in mice and rats]. AB - Ovarian bursal membranes were dissected using a bipolar coagulator during embryo transfer to the oviducts of pseudopregnant female mice and rats. The bipolar coagulator allowed accurate, fine coagulation of small vessels and wide dissection of ovarian bursal membranes without damage to the oviducts or ovaries. PMID- 2242774 TI - Pathology of sternal deformity in the Sprague-Dawley rat. AB - Pathological examination of two 12-week-old male Sprague-Dawley rats revealed bending of the sternebrae. Grossly, the sternebrae distal to the third sternebra were bent towards the underside, and the episternal extremity was turned towards the head. Microscopically, the 4th sternebra was observed to have slipped behind the third sternebra, and fractures of the episternal cortex and slanting of the episternal cartilage were also observed. PMID- 2242773 TI - Antinucleolar autoantibody induced in mice by mercuric chloride--strain difference in susceptibility. AB - Eight inbred mouse strains were examined for their reactivity to the induction of antinucleolar autoantibody (AnuA) by mercuric chloride (MC). According to the positive ratio and titer of AnuA induced, the strains were grouped into high-, moderate-, low-, and non-responders. Since the susceptibilities to MC were different among strains having the same H-2 haplotype, involvement of H-2 unlinked gene (s) in AnuA induction by MC was suggested. PMID- 2242775 TI - Hypoplasia of one kidney in a Sprague-Dawley rat. AB - Pathological examination of a 4-week-old male Sprague-Dawley rat revealed hypoplasia of the left kidney. Grossly, the left kidney exhibited hypoplasia associated with absence of the ureter on the same side. Histologically, components of the cortex and medulla were mingled in the tissue, and the glomeruli and convoluted tubules were scattered in disorder, and connective tissue proliferation was also observed. The papilla and pelvis could not be identified. PMID- 2242776 TI - Study on cross-reactivity to the para group. AB - In 80 patients, positive to at least one hapten of the para group (para phenylenediamine, diaminodiphenylmethane, benzocaine, PPD mix), patch tests were carried out with freshly prepared solutions of para-phenylenediamine (PPD) and of 3 selected aromatic compounds related structurally to PPD (para-aminophenol, ortho-aminophenol, hydroquinone). The number of positive reactions correlated with the rate of decomposition of the substances as evaluated by high-pressure liquid chromatography. PPD, which was almost decomposed after 24 h, gave the highest number of positive reactions, followed by ortho-aminophenol and by para aminophenol, while hydroquinone, which was oxidized to the extent of 35%, did not give any reactions. To evaluate if a different rate of oxidation can modify the patch test response, in the same patients and in 10 normal volunteers, tests were carried out with PPD solutions containing the oxidizing agent silver oxide (0.1%). By this procedure a significant increase in the number of positive responses was observed. The results suggest that the rate of decomposition and therefore the amount of quinone(s) generated, might be the key to eliciting patch test responses to oxidizable aromatic haptens. PMID- 2242777 TI - Guidelines for histopathologic diagnosis of plantar malignant melanoma. Two dimensional coordination of maximum diameters of lesions and degrees of intraepidermal proliferation of melanocytes. AB - Detection of early lesions of malignant melanoma is highly important for the improvement of the prognosis. However, diagnosis of early malignant melanoma is not easy and is often discordant even among expert dermatopathologists. In this study, we propose guidelines for the histopathologic diagnosis of plantar malignant melanoma and malignant melanoma in situ on the sole. They are formulated with two-dimensional coordination of maximum diameters of the lesions and degrees of intraepidermal proliferation of solitary-arranged melanocytes. The guidelines are simple and reproducible, and surely contribute to the accurate diagnosis of early plantar malignant melanoma. PMID- 2242778 TI - Hair growth in human split-thickness skin grafts transplanted onto nude rats: the role of cyclosporin. AB - To date, there have been no descriptions of hair growth following transplantation of human split-thickness skin grafts (HSTSG) to congenitally athymic (nude) mice or rats. Recently, we noted hair growth in HSTSG from scalp skin (HSTSG-SS) transplanted onto rats treated with ciclosporin (CS). By definition, HSTSG-SS of 0.4 mm had all the anagen hairs cut from the papillae. Two months after engraftment, there was histological evidence of the formation of new papillae. Density of hair correlated with thickness of HSTSG, i.e. there were more hairs/square centimeter in HSTSG-SS of 1 mm thickness than in those of 0.4 mm thickness. New hairs appeared on an average of 1 cm2/week in HSTSG-SS that were 1 mm thick; by 10 weeks, the mean density was 7.9 hairs/cm2. In the thinner grafts, the density was 3.5 hairs/cm2 (p less than 0.025). The rate of growth in the thicker grafts ranged from 0 to 0.25 mm/day, with an average of 0.1 mm/day. At 10 weeks after grafting, the hairs had a mean length of 4.4 mm in the thicker and 1.7 mm in the thinner grafts (p less than 0.001). The average diameter of the hair shafts was 0.05 mm at the various times tested. These observations identify a previously unrecognized process of hair growth and present an in vivo model to study human hair growth process, including the role of CS in hair growth. PMID- 2242779 TI - Delusional parasitosis as 'folie a trois'. AB - Delusional parasitosis can apparently run in families. Three out of 9 members of a German family were fully convinced that their skin had been invaded by 'tiny running animals' even though there was no physical evidence of any infestation. Although the family was reluctant to be injected with neuroleptic drugs as this would have been an acknowledgement that their symptoms were in fact of psychological origin, they eventually agreed to be treated. When last contacted, 3 years after diagnosis, they still believed in the existence of the parasites but admitted that some of their symptoms had improved. PMID- 2242780 TI - Nail biting and picking as a possible cause of longitudinal melanonychia. A study of 6 cases. AB - Examination of individuals affected by onychotillomania led us to describe a new cause of longitudinal melanonychia (LM) of the finger-nails. Damage of the finger nails was caused both manually and by chewing. The nail cuticles were usually pushed back, and biting caused pressure damage of the base of the nail. It is likely that finger-nails respond similarly to toe-nails and the matrix melanocytes can be stimulated by trauma. Such stimulation can apparently persist long after cessation of the trauma. Histological examination of the nail plates demonstrated that the pigment was melanin. In the matrix an increase in melanin content of melanocytes was found without melanocytic proliferation. LM due to onychotillomania should not be overlooked. PMID- 2242782 TI - Topical alpha-interferon in recurrent genital herpes simplex infection. A double blind, placebo-controlled clinical trial. AB - We conducted a double-blind placebo-controlled clinical trial on 98 subjects to assess the efficacy of two strengths of topical human leukocyte alpha-interferon, 10(4) and 10(6) IU/g in a 1% nonoxynol-9 base, in the treatment of recurrent genital herpes simplex virus (HSV). The study medication was applied during the prodromal phase or at the first sign of recurrence of the infection. The high dose alpha-interferon was found to be significantly more effective than the low dose interferon and placebo with respect to the duration of viral shedding as well as in reducing the time to the end of all subjective symptoms, including pain, burning and itching. No difference between the three groups was found in times to crusting or healing. Further studies of topical interferon in the treatment of HSV and other viral infections are merited. PMID- 2242781 TI - Xeroderma pigmentosum group D patient bearing lentigo maligna without neurological symptoms. AB - A 35-year-old Japanese female patient with xeroderma pigmentosum (XP), registered as XP114TO, was assigned to complementation group D by the cell fusion complementation test. The patient had manifested moderate solar sensitivity and freckles by the age of 6 years. The skin phototest using 290- and 300-nm monochromatic ultraviolet (UV) light revealed slightly lowered minimal erythema doses at 24 h after irradiation. The XP114TO skin fibroblasts exhibited about the 6-fold higher sensitivity to the lethal effect of 254-nm UV as did normal cells. Unscheduled DNA synthesis (UDS) induced in XP114TO cells by 254-nm UV (10 J/m2) was 33% of normal, falling into the group D range of 25-50% UDS. The patient developed lentigo maligna on the right side of the nose. Unlike the typical XP group D cases in the West, she showed no neurological abnormalities. PMID- 2242783 TI - Poikiloderma, alopecia, retrognathism and cleft palate: the PARC syndrome. Is this an undescribed dominantly inherited syndrome? AB - We report a clinicopathological observation concerning a man and his son affected by the same disease. The main cutaneous lesions included poikiloderma congenitale and generalized alopecia respecting the pubic area. These anomalies were associated with cleft palate and Robin sequence in the boy. The main histological changes consisted in a marked atrophy of hairs with persistence of sebaceous glands. In sun-exposed areas, we found colloid bodies, melanophages and hyperplasia of the elastic tissue network. Those features resembled those of the Rothmund-Thomson syndrome, but the phenotype and the apparent dominant mode of inheritance exclude this possibility. A new genodermatosis, related with, but distinct from the Rothmund-Thomson syndrome is suspected, for which the acronym PARC syndrome is proposed. PMID- 2242784 TI - Hereditary benign telangiectasia: a congenital type. AB - Hereditary benign telangiectasia (HBT) is inherited in an autosomal dominant fashion, and in all the cases reported in the past it developed after birth. We describe 3 congenital cases of HBT in the same Japanese family: a 29-year-old father and his 5-month- and 2-year-old daughters have had scattered erythematous patches of various sizes in diameter since birth. PMID- 2242785 TI - Hyperpigmentation induced by UVB at the application site of estradiol. AB - We report a case of a 48-year-old woman who presented with chronic essential pruritus and was successfully treated with the transdermal estradiol system because of menopausal discomfort. Suberythemogenic UVB phototherapy was proposed to the patient in order to control her pruritus. She developed hyperpigmentation at the application site of estradiol. To the best of our knowledge, this is the first report suggesting a direct relationship between estrogen and melanin synthesis in humans. PMID- 2242786 TI - Pigmented nail streak associated with Bowen's disease of the nail matrix. AB - We described a 59-year-old male physician with Bowen's disease occurring on the nail matrix of his right 5th finger. The rapid growth of the pigmented nail streak accompanied by nail deformity led us to consider the possibility of subungual melanoma clinically. Histologic features, however, were compatible with those of Bowen's disease accompanied by melanocytes with melanin-rich long dendrites in the nail matrix. We speculate that his occupational exposure to X rays for 25 years played an important role in the pathomechanism of the present case. PMID- 2242787 TI - Massive lymphomatous nail involvement in Sezary syndrome. AB - The case of a 65-year-old man affected by chronic erythroderma due to Sezary syndrome and massive lymphomatous infiltration of the nails is reported. The clinical features of the nail lesions, consisting in thickening and discoloration of the nail plates, were not diagnostic. The nail biopsy showed a typical epidermotropic T cell lymphomatous involvement of all the nail constituents. Immunohistochemical characterization of the nails and skin lymphomatous infiltration showed identical results, confirming the neoplastic etiology of both the chronic erythroderma and the nail dystrophy. PMID- 2242788 TI - Symmetrical interdigital hyperkeratosis of the hands with scrotal tongue and highly arched palate. PMID- 2242789 TI - Photochemotherapy plus squaric acid dibutylester in alopecia areata treatment. PMID- 2242790 TI - Water-induced itching. AB - In this paper the current knowledge on water-induced pruritus is reviewed. To the present, three forms, namely aquagenic pruritus (AP), aquagenic pruritus of the elderly (APE) and water-related itching in polycythemia rubra vera (PRV), have been recognized. Despite clinical similarities it appears that the pathophysiology is different in the three forms. The currently most effective treatment for AP is addition of sodium bicarbonate to the water, control of xerosis with emollients for APE and aspirin for water-induced itching in PRV. PMID- 2242791 TI - Frictional properties of human forearm and vulvar skin: influence of age and correlation with transepidermal water loss and capacitance. AB - The dynamic friction coefficient between skin and a Teflon probe and its correlation with age, body weight, height, transepidermal water loss and skin capacitance was studied in vulvar and forearm skin of 44 healthy female volunteers. The friction coefficient of vulvar skin was 0.66 +/- 0.03 (mean +/- SEM) compared to that of forearm skin of 0.48 +/- 0.01. The difference was highly significant (p less than 0.001). Multiple-regression analysis showed that the vulvar skin friction coefficient was significantly correlated with capacitance as an indicator of stratum corneum hydration (p less than 0.01) but not with age, weight, height or transepidermal water loss. It is concluded that the high friction coefficient of vulvar skin may be due to the increased hydration of vulvar skin. Age-related differences seem to exist for transepidermal water loss and friction coefficient in forearm but not in vulvar skin. PMID- 2242792 TI - Levels of soluble interleukin-2 receptors correlate with the severity of atopic dermatitis. AB - Levels of soluble interleukin-2 receptors (sIL-2R) were measured as a marker of lymphocyte activation in serum of 37 patients with atopic dermatitis (AD) and of 16 patients with psoriasis vulgaris (PV), all individuals being hospitalized in the Zurich High Mountain Clinic of Davos-Clavadel (altitude 1,600 m above sea level). Measurements were performed at admission and at discharge. The PV patients served as a control group. As a further control, 20 AD patients from the Department of Dermatology in Zurich (altitude 400 m) were also evaluated. The serum sIL-2R concentration in AD patients at admission was significantly elevated in comparison with PV patients and was highly correlated with the severity of the cutaneous involvement. Comparing the 'extrinsic' and 'intrinsic' types of AD, no significant differences of sIL-2R levels were found. The sIL-2R concentrations dropped at discharge. These results suggest that the measurement of the sIL-2R level could be a marker of disease activity. PMID- 2242793 TI - Induction of labour: the effect of vaginal prostaglandin or i.v. oxytocin--a matter of time only? AB - Ninety-one pregnant women with unfavourable cervix (Bishop score no higher than 6) were randomly allocated to induction of labour with either prostaglandin E2 suppositories 2.5 mg 1-2 a day or i.v. oxytocin 4-32 mU/min. The induction procedure was carried on for 2 days. For statistical comparison of efficacy, life table analysis and the logrank test were used with vaginal delivery as the aimed 'event'. Prostaglandin suppositories were more efficient after 12 h (p less than 0.025) and 24 h (p less than 0.005), whereas no difference in efficacy was observed after 48 h. Vaginal delivery was obtained within 48 h in 74% of the women in the prostaglandin group and in 70% in the oxytocin group. No difference was observed in methods of delivery or neonatal Apgar scores, though, in neonates delivered vaginally within 2 days, lowered umbilical artery blood pH values were found after prostaglandin E2 suppositories (p less than 0.05). The patients attitude toward the method of induction was highly in favour of the prostaglandin suppositories. Prostaglandin E2 suppositories are considered excellent for induction of labour if delivery has to be within 24 h, whereas the two methods are equally effective after 48 h. PMID- 2242794 TI - Computerized analysis of antepartum fetal heart rate tracings in normal pregnancies (version 88/2.29). AB - A computerized system is developed for the interpretation of antepartum fetal heart-rate monitoring. Various parameters are described to define the cardiotocograms. The pattern of the tracing is defined as saltatory, undulatory, reduced undulatory or silent according to the results of the spectrum analysis. Three different baselines including simple average baseline, real baseline and basecurve are described for each tracing. Spontaneous and fetal movement related accelerations and decelerations are also defined. Tracings from 33 normal pregnancies with normal outcome were studied and the distribution of parameters for each gestational week (28th to 40th) was defined. The real baseline of fetal heart rate was 141.5 +/- 8.5 between the 28th and 40th gestational week. 75% of the cardiotocograms were found to obtain fetal movement. It has also been observed that in normal pregnancies the general pattern of the tracings is undulatory or undulatory/saltatory. PMID- 2242795 TI - Development and application of a simple expert system for the interpretation of the antepartum fetal heart rate tracings (version 88/2.29). AB - A simple expert system is developed for the interpretation of antepartum fetal heart rate tracings. The perinatal expert chose to use the phrase 'Fetal Reserve' to describe what the cardiotocogram is indirectly measuring. Our analysis program gives numerical values to each CTG such as 5, 4, 3, 2.5, 2 and 1 corresponding to the fetal reserve conditions of good, satisfactory, probably satisfactory with uncertainty, borderline, decreased, and critical respectively. This study consists of 33 normal pregnancies with normal outcome. Each patient is followed by our computerized system biweekly from the 28th to the 38th gestational week and weekly there after. The expert system's decision for 28th, 30th, 32nd, 34th, 36th, 38th, 39th and 40th gestational weeks were 3.3 +/- 1.0, 3.8 +/- 0.7, 3.8 +/ 1.0, 4.1 +/- 0.9, 4.1 +/- 0.7, 3.6 +/- 1.0, 4.2 +/- 1.0, 3.8 +/- 0.9 and 3.4 +/- 1.2, respectively. In this study, we have used confusion matrix to determine the normal, security, and danger zones according to the perinatal expert and the expert system and the discriminatory power of the system is found to be highly significant statistically (Q = 221). We also showed that the passive test (non stress test) in normal pregnancies has demonstrated false positive results in 4.2 and 9.3% of the cases according to the evaluations of the perinatal expert and the expert system, respectively. PMID- 2242797 TI - Coexistence of spermatozoa morphological abnormalities in the semen of subfertile men with varicocele. AB - Spermatozoal morphology in semen specimens from 107 subfertile men with varicocele, aged from 18 to 50 years, were evaluated from Papanicolaou-stained smears, in order to investigate: (a) the frequency of abnormalities in the neck and tail of spermatozoa with an abnormal head; and (b) the ability of prediction of the morphology of one sperm part when the morphology of another is known. It was found that: (1) Morphological abnormalities in the neck are significantly more frequent (p less than 0.01) in spermatozoa with an abnormal head than in spermatozoa with a normal head. (2) Morphological abnormalities in the tail and cytoplasmic droplet are also more frequent, although not significantly, in spermatozoa with an abnormal head. (3) The proportional reduction in error (PRE) was low in all cases. Our results show that spermatozoa with abnormal heads present morphological abnormalities of their other parts more often than spermatozoa with normal heads. However, no prediction can be made on the nature of the morphology of a part of a spermatozoon on the basis of knowledge of the morphology of another of its parts. PMID- 2242796 TI - Chlamydial IgG and IgA in serum and follicular fluid among patients undergoing in vitro fertilisation. AB - The point prevalence of IgG and IgA antibodies to Chlamydia was analyzed in serum and follicular fluid in 63 patients undergoing in vitro fertilisation (IVF) in comparison to sera of 298 healthy women by the single serovar (L2) inclusion immunoperoxidase assay (IPA). The presence of specific IgG and IgA to Chlamydia in follicular fluid was demonstrated. No statistical association was found between the presence of specific Chlamydia IgG and IgA in serum and follicular fluid to oocyte fertilization. The positive predictive value for mechanical infertility of Chlamydia IgG at titers of greater than or equal to 128 and IgA titers at greater than or equal to 16 was 91 and 92%, respectively, in this high risk group for mechanical infertility. Multiple regression analysis singled out Chlamydia IgG levels as a major contributor to the variance between the groups of infertile patients. PMID- 2242798 TI - Carcinoma of the stomach associated with the pregnancy: two case reports. AB - Two case reports on carcinoma of the stomach associated with pregnancy are presented. In both cases, the main symptoms were persisting hyperemesis, nausea and weight loss. Both mothers succumbed within a year after their pregnancy, but the infants born by Cesarean section are doing well. The diagnostic and therapeutic difficulties which are encountered when a carcinoma complicates a pregnancy are discussed. PMID- 2242799 TI - Previous obstetric history and subsequent preterm delivery in Greece. AB - A total population sample of 6524 multigravid women who were certain of the date of their last menstrual period was obtained from the population-based Greek National Perinatal Survey of April 1983. The sample was used to determine the associations between features of the maternal obstetric history and preterm delivery. There were significant associations between preterm delivery and previous fetal losses, whether early (miscarriages and/or induced abortions) or late (stillbirths). For mothers who had experienced miscarriage(s), induced abortion(s) or stillbirth(s) the odds ratios were 1.40, 1.36 and 1.15, respectively, compared with mothers without any fetal loss. The odds ratio increased substantially with the increasing number of losses and reached 5.60 for the small group of mothers who had had prior miscarriage, termination and stillbirths. The results changed very little when the socioeconomic characteristics of the family were taken into account. PMID- 2242800 TI - Proceedings of the Consensus Conference on Therapeutic Endoscopy in Bleeding Ulcers. March 6-8, 1989. PMID- 2242802 TI - Endoscopic risk factors for bleeding peptic ulcer. PMID- 2242801 TI - Therapeutic endoscopy and bleeding ulcers. Clinical risk factors. PMID- 2242803 TI - Therapeutic endoscopy and bleeding ulcers: historical overview. PMID- 2242804 TI - Pathophysiology of bleeding lesions. PMID- 2242805 TI - Therapeutic endoscopy and bleeding ulcers. Efficacy criteria--outcome of therapy. PMID- 2242806 TI - Introduction to endoscopic therapy for bleeding peptic ulcers. PMID- 2242808 TI - Argon laser/CO2 treatment of bleeding ulcers. PMID- 2242807 TI - Therapeutic endoscopy and bleeding ulcers. Nd:YAG laser: the pro approach. PMID- 2242809 TI - Monopolar and electrohydrothermal treatment of upper gastrointestinal bleeding. PMID- 2242810 TI - Therapeutic endoscopy and bleeding ulcers. Bipolar/multipolar electrocoagulation. PMID- 2242811 TI - Heat probe for hemostasis of bleeding peptic ulcers: technique and results of randomized controlled trials. PMID- 2242812 TI - Injection therapy for the control of bleeding ulcers. PMID- 2242813 TI - Topical therapy for the control of gastrointestinal bleeding. PMID- 2242814 TI - Therapeutic endoscopy and bleeding ulcers: methodology. PMID- 2242815 TI - Consensus statement on therapeutic endoscopy and bleeding ulcers. Consensus Development Panel. PMID- 2242816 TI - Epidemiology of upper gastrointestinal bleeding. PMID- 2242818 TI - [The early development of Jacobson's organ in the nasal cavity of the rat before the inception of the secondary palatal development]. AB - The early development of Jacobson's organ was studied by means of a series of embryos of the rat which were of various ages and exactly dated. Already at the youngest stage of those rats, the nasal cavity is just an open groove, the organ is a thickened epithelial layer at the medial nasal process. Only 15 h later, while the nasal grooves start to close from caudal to rostral, Jacobson's organ has acquired the shape of a deep, long cleft, situated within the broad nasal opening. On the 13th d of fetal life, a complete, caudally closed nasal cavity appears. By the means of fundamental growth changes, the already well developed organ has become shifted to a more caudal position and lies now above the primary palate. A shorter caudal part of the still cleft-like organ just starts to close itself thus forming its typical tube-like structure. Moreover strong nerve bundles running from Jacobson's organ to the brain indicate that in the meantime a sensory epithelium can be distinguished. Up to the 15th d of development, the tube-forming process of Jacobson's organ is completed. Parallel to this procedure, the surrounding nasal cavity acquires a caudal apertura nasalis interna by the rupture of the membrana bucconasalis while Jacobson's organ still lies above the rostral primary palate. Primary in the medial, somewhat later in the lateral part of the nasal cavity, first outlines of cartilage appear, visible as dense cell formations. Together with this, the paraseptal cartilage, in these stages closely connected to the septal cartilage, develops quite early. Between the 14th and 15th d of its fetal life, the flat, tube-formed Jacobson's organ of the rat gets turned from a primary horizontal into a vertical position, which brings its sensory epithelium to the medial side. It is assumed that this happens for functional reasons. Because of the obviously early and progressive development of Jacobson's organ within that of the nasal cavity, it seems to be probable that already the origin of the nose, the olfactory placodes, are determined in the directions both of the nasal cavity and of Jacobson's organ. Furthermore the results demonstrate an early preferential development of Jacobson's organ in comparison to that of the surrounding nasal cavity. PMID- 2242817 TI - [Craniogenesis in the laughing gull (Larus ridibundus L.). The reconstruction of the basic plan of the bird]. AB - To contribute to the knowledge of the cranium of older bird embryos, the chondrocranium and osteocranium of the Black-headed Gull (Larus ridibundus) are described. The chondrocranium of the Black-headed Gull is compared with the chondrocranium of other bird species with special consideration of functional and phylogenetic aspects. As a result a "grundplan" of the bird chondrocranium is reconstructed. Most of the chondrocranial autapomorphies of birds are connected with the enlargement of the eyes, the development of a beak and a prokinetic skull, and the reduction of the olfactory system. PMID- 2242819 TI - [Preliminary study of an interdisciplinary examination of the body height proportions of Germans in the 19th century and of the influence of living conditions. I. Introductory justification, problems and preliminary studies based on authentic sources from the political districts from northern Germany to Wurttemburg]. AB - Researches about the influences of the nutritional conditions on body-height need interdisciplinary co-operation of Anthropology, History, and Dietetics. Such a team will be difficult succeed in joining. Especially interesting for human sciences are nutritional-constitutional researches on German populations in the 19th century, because in this century multifarious varieties exist within the German settlement. Author hopes, that preliminary original researches and first trends in results facilitate the joining of such an interdisciplinary team. In part I of this inquiry, the necessity for nutritional-constitutional researches are justified, problems are treated and mustering-statistics, the most important data-material, are collected for the political regions of that time from North to the kingdom Wurttemberg. The kingdom Wurttemberg of course is the political region with the most continuous data-series, but the data-material is poor on body-height-means and needs new statistical treatments. Less data are particularly available from the middle of the German settlement. PMID- 2242820 TI - On the origin of the so-called Meckelian ossicles in the nasal skull of odontocetes. AB - Although Cave (1987) accepts the theory that the Meckelian ossicles originate from the maxilloturbinals, evidence given in his study in fact supports the opinion of Klima and van Bree (1985) that the Meckelian ossicles arise from elements of the nasal floor, solum nasi, of the embryonic nasal capsule, in particular from the lamina transversalis anterior and the cartilago paraseptalis. PMID- 2242821 TI - [Metric studies of the dermal ridges of the palm in relation to handedness]. AB - Palm prints of 394 right-handers and 356 non-right-handers (left-handers and ambidexters) were evaluated regarding distance ad, ulnar shift, and relative horizontal triradius distance. Comparison between handedness groups produced some significant differences. The "graded distinction of dermatoglyphic traits" which was found in an earlier study has been confirmed. It has been suggested a modification of terminology for the position of axial triradii. PMID- 2242822 TI - [The effect of morphologic variety on the biostatics of lumbosacral transition]. AB - Variants shown by the orientation of the cover-plate and of the superior articular facets of the sacrum have a considerable influence on the lumbosacral biostatistics. This can be illustrated by parallelograms of forces. If we assume a certain force stressing upon the sacrum, we are able to calculate the distribution of stress upon the cover-plate and the articular facets by help of the size and the orientation of these weight bearing faces. PMID- 2242823 TI - [Comparative anatomic studies of the tongue of Pan troglodytes (Blumenbach, 1799) and other primates. I. The chimpanzee tongue]. AB - This study was carried out on a comprehensive collection of tongues of Pan troglodytes. Material of tongues of Tupaia glis, Microcebus murinus, Chirogaleus major, Lemur catta, Galago crassicaudatus, Cebus apella, and Macaca mulatta were used for comparison of the different stages of the development of the papilla foliata. The tongue of Pan exhibits longitudinal growth correlated with the growth of length of the jaws and individual age. A typical foramen caecum as it occurs in man was gross anatomically not recognizable. Seldom a small circular depression appeared in the midline close to the papilla circumvallata centralis which could be the remnant of the foramen caecum. There is a remarkable accumulation of papillae filiformes and fungiformes at the apex linguae; the same seems to be true for other genera of primates. It is self-explanatory that the accumulation of papillae makes the tip of the tongue a particularly sensitive area; this has been found to be true even in man. One specimen of the prenatal age just before term was studied. It exhibited remarkably elongated, thread-like papillae, their function is unknown as yet. They are no longer present in a newborn specimen of 4 d of age. In the aboral part of the dorsum linguae, a special kind of papillae occur; they are flat lobes which carry moderately elongated, tiny processes at their free margin. The function of these papillae is unknown; taste buds are absent. PMID- 2242824 TI - Enhanced ristocetin-induced von Willebrand factor binding to platelet glycoprotein Ib in patients with steroid-responsive nephrotic syndrome. AB - To elucidate the mechanism of enhanced ristocetin-induced platelet aggregation (RIPA) in steroid-responsive nephrotic syndrome (SRNS), plasma levels of von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor (RCof) were examined in 6 patients and the amount of ristocetin-induced vWF binding to platelets was determined. At the initial or relapse stage, the plasma vWF:Ag level was 415 +/- 137% and the RCof level was 364 +/- 117%. The ratio of RCof/vWF:Ag was 0.90 +/- 0.15 and no abnormalities of vWF:Ag multimers were observed, indicating that neither functional nor structural abnormalities were present in patient's plasma. The amount of ristocetin-induced normal vWF binding to nephrotic washed platelets, when ristocetin was used at concentrations of 0.5, 0.75, and 1.0 mg/ml, was 152-163% above the binding to normal platelets. In addition, nephrotic washed platelets resuspended in either normal or nephrotic plasma aggregated at a low concentration of ristocetin (0.75 mg/ml) which did not induce aggregation of normal platelets. In accordance with these observations, the decrease of Alcian blue 8GX binding to platelets, reflecting diminished surface negative charge, was also observed. These results appear to indicate that the plasma vWF level and the altered surface-negative charge in platelets both contribute to heightened vWF binding to GPIb, thus lowering the ristocetin concentration required for RIPA in SRNS. PMID- 2242825 TI - Glycometabolic control and fibrinolysis in diabetic patients. AB - We investigated 148 diabetic patients with regard to their relationship between fibrinolysis (D-dimer and plasminogen activator inhibitor; PAI) and glycometabolic control (HbA1c, HbA1 and fructosamine). The percentage of moderately controlled patients as indicated by HbA1c, HbA1 and fructosamine is relatively high (29.7, 41.7 and 30.4%, respectively). Simultaneously, the D-dimer and PAI levels turned out to be enhanced in 30.8 and 22.4% of the patients. There was a positive nonsignificant correlation between D-dimer and HbA1c, a highly significant negative correlation between D-dimer and HbA1 and a nonsignificant negative correlation between D-dimer and fructosamine. According to the upper limits of the distinct reference ranges for HbA1c, HbA1 and fructosamine, we splitted up the D-dimer results and calculated the mean D-dimer values belonging to each category. Comparing the D-dimer means for each parameter, we separately obtained significant differences of the D-dimer means between the lower and higher HbA1 and fructosamine groups, whereas in the case of HbA1c the mean D dimer values of the categories under and over 9% showed no significant difference. For PAI, we found only weak nonsignificant positive correlations to D dimer and fructosamine and weak but highly significant correlations to HbA1c. These results are indicative for an increase of PAI with diminished glycometabolic control as measured with the HbA1c and fructosamine level. Both D dimer and PAI showed positive, highly significant correlations to the age of the diabetic patients, whereas HbA1c and fructosamine were age independent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242826 TI - Structure-specificity of the genotoxicity of some naturally occurring alkenylbenzenes determined by the unscheduled DNA synthesis assay in rat hepatocytes. AB - A number of alkenylbenzenes related to safrole and estragole are known to be hepatocarcinogenic in rats and/or mice, apparently by a genotoxic mechanism. However, they are not bacterial mutagens in the Ames test. We have studied the ability of a series of carcinogenic and non-carcinogenic congeners to induce unscheduled DNA synthesis (UDS) in freshly isolated rat hepatocytes in primary culture. The cytotoxicity of these compounds was assessed by lactate dehydrogenase leakage. There was an excellent correlation between UDS induction and known rodent hepatocarcinogenicity, with safrole, estragole and methyleugenol all inducing UDS. Anethole, isosafrole, eugenol and allylbenzene, for which evidence of carcinogenicity is equivocal or negative, did not induce UDS. All compounds were markedly cytotoxic at concentrations between 10(-3) and 10(-2) M, irrespective of their structural features. The data are discussed with reference to the known structure dependence of the disposition of the alkenylbenzenes, notably their metabolic activation, with which there are excellent correlations. The demonstration of the genotoxicity of rodent hepatocarcinogenic alkenylbenzenes in cells cultured from the in vivo target organ will allow the direct investigation of factors influencing these processes and facilitate the safety evaluation of these important natural flavours. PMID- 2242827 TI - Urinary and bladder responses to immobilization in male rats. AB - Immobilization of groups of five to nine male rats for 2-5 days results in a 50% increase in urinary bladder fresh weight compared with normally caged controls. The increase in urinary bladder weight was not due to tissue oedema and was accompanied by epithelial hyperplasia in some urinary bladders. Immobilization did not alter total urine volume, but it did decrease the frequency of urine voiding and doubled the mean urine weight/voiding. Thus, bladder distention caused by the increased volume per voiding caused a rapidly induced increase in bladder tissue growth, and was accompanied by an increase in bladder epithelial cell division. PMID- 2242828 TI - Effects of Escherichia coli lipopolysaccharide on nitrate synthesis and on nitrosation of proline in rats. AB - Male Ola:SD rats were fed purified diets containing 5 or 20% lactalbumin as the protein source, with or without concomitant administration of Escherichia coli lipopolysaccharide (50-250 micrograms/kg, ip), and changes in 24-hr urinary nitrate excretion, plasma urea, plasma-nitrate pool size and 24-hr urinary nitrosoproline excretion were measured. Urinary nitrate and urinary 14C nitrosoproline excretion (after oral [14C]proline administration) were significantly greater for rats receiving the high-protein diet compared with those on the low-protein diet. The co-administration of lipopolysaccharide increased nitrate excretion in both diet groups (although the increase was greatest (relatively) in the animals fed 5% lactalbumin), but did not significantly alter urinary nitrosoproline excretion by either group. Plasma urea concentrations and plasma-nitrate pool size were increased by a high-protein diet and/or lipopolysaccharide administration. These findings suggest that treatments which alter the availability of nitrate in vivo are not necessarily associated with increased nitrosation of proline. PMID- 2242829 TI - Toxicological evaluation of morning glory seed: subchronic 90-day feeding study. AB - Diets containing 0.8, 2.53 and 8.0% field variety morning glory seed were fed to male and female rats (20 per group) in a 90-day subchronic feeding study. Gross clinical observations, body weight, and feed and water intake were recorded weekly. At 90 days, all surviving rats were autopsied, organs were weighed, and blood chemistry analyses, haematology, and bone-marrow evaluation for evidence of clastogenic effects were performed. Tissues from control (0% seed) and high-dose (8.0% seed) rats were examined histologically. Effects of morning glory seed were noted mainly in the high-dose group of both sexes. These included increases in mortality, feed consumption (on a body-weight basis), water consumption, serum alkaline phosphatase and potassium, white blood cell count, and brain and liver weights (as a percentage of body weight); body-weight gain and serum glucose were decreased. Significant changes seen in high-dose females alone were: increased haemoglobin, serum constituents (urea nitrogen, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, and ornithine carbamyl transferase), and organ weights (heart, kidney, spleen and pancreas as a percentage of body weight), and decreases in serum albumin, total protein, albumin:globulin ratio, and calcium. Significant changes occurring in high-dose males alone were: increased testicular weight (as a percentage of body weight), increased serum phosphorus, and decreased serum cholesterol. Liver degeneration in the high-dose females was greater than that in the controls. Mortality at 8.0% seed in the diet was 40% in males and 10% in females. At 0.8% seed, the only parameter that differed significantly from that of the controls was a final body-weight reduction in females without a corresponding reduction in feed consumption. PMID- 2242830 TI - Steric effects on the haemolytic activity of aromatic disulphides in rats. AB - Certain derivatives of diphenyl disulphide are known to cause haemolytic anaemia in rats, by a mechanism possibly involving intra-erythrocytic redox cycling with concomitant generation of 'active oxygen' species. In ring-substituted diphenyl disulphide derivatives, electronic effects of substituents have been shown markedly to affect the rate of 'active oxygen' production in vitro and toxicity in vivo. In the present study, the influence of steric effects of substituents on these parameters has been investigated. The severity of the haemolysis induced in groups of seven rats by oral dosing with 4,4'-dimethoxydiphenyl disulphide and 4,4'-dimethyldiphenyl disulphide at doses of 500 mumol/kg/day for 6 days was greater than that of the 2,2' isomers and the haemolytic activity of a series of 2,2'-dialkyl derivatives decreased with increasing size of the alkyl group. In vitro, the haematin-catalysed oxidation rates and the rates of redox cycling of the corresponding thiols in the presence of glutathione were similarly influenced by steric hindrance. The structure-activity relationships identified in the present investigation, together with knowledge of the electronic effects of substituents, should permit accurate prediction of the toxicity of new or untested aromatic thiols and disulphides. PMID- 2242831 TI - Regional distribution of dopamine beta-hydroxylase and monoamine oxidase in the brains of rats exposed to manganese. AB - The regional distribution of dopamine beta-hydroxylase (DBH) and monoamine oxidase (MAO) in rat brain was compared in control rats and rats given manganese in drinking-water (1 mg Mn/ml) for 30 days. In treated rats there was a significant accumulation of Mn in almost all regions of the brain except the hippocampus. Accumulation was highest in the hypothalamus, cortex and striatum. After Mn exposure, DBH activity was significantly decreased (in comparison with the controls) in the hypothalamus, striatum, mid-brain, cerebellum and cortex. A significant increase in MAO activity was found in the striatum, hypothalamus, mid brain, hippocampus and medulla. The effects of Mn on these enzymes suggests the involvement of biogenic amines like dopamine, norepinephrine and serotonin during Mn toxicity. The effect of Mn is region specific and in certain regions the action of Mn on DBH differs from that on MAO. These different effects of Mn on DBH and MAO in different regions of the brain might explain the variable symptoms seen in Mn-induced neurotoxicity in humans. PMID- 2242832 TI - Acute and sub-acute inhalation toxicity of germanium metal powder in rats. AB - An acute (4-hr) and a sub-acute (4-wk) inhalation toxicity study of germanium metal powder (purity 99.8%, mean particle size 2.0-2.4 microns) were carried out in young adult Wistar rats. Exposure of five male and five female rats to 3.86 or 5.34 g/m3 for 4 hr resulted in the death of one rat at each exposure level. Four groups of five male and five female rats were exposed to 0, 9.9, 65.1 or 251.4 mg/m3 for 6 hr/day, 5 days/wk for 30 days. Two additional (recovery) groups of five male and five female rats exposed to 0 or 251.4 mg/m3 were kept untreated for 31 days after exposure. At the end of the treatment period, fasting blood glucose was decreased in males exposed to the high concentration. In females of this group, blood creatinine and urea levels, and urine volumes were increased, but urine density was decreased. Increased blood creatinine levels and urine volume and decreased urine density were also observed in females exposed to 65.1 mg/m3. The absolute and relative lung weights were increased in rats in the mid and high-concentration groups. Histopathological examination revealed: accumulation of particulate material in the lungs of all treated groups, accumulation of alveolar macrophages in the mid- and high-concentration groups, and alveolitis mainly in the high-concentration group. After the 4-wk recovery period, urine volume was increased in males that had been exposed to germanium. In exposed rats of both sexes, lung weights were still increased and histopathological changes were present, but to a lesser extent than at the end of the exposure period. It was concluded that the 4-hr LC50 value of germanium metal powder in rats is greater than 5.34 g/m3. The no-adverse-effect level in the 4-wk study was 9.9 mg/m3 air. PMID- 2242833 TI - Long-term toxicity/carcinogenicity of musk xylol in B6C3F1 mice. AB - The long-term toxicity/carcinogenicity of musk xylol, a synthetic nitro musk, was examined in B6C3F1 mice of both sexes. Musk xylol was administered at dietary levels of 0 (control), 0.075 or 0.15% for 80 wk. The overall tumour incidences in all treated groups of both sexes were significantly higher than those in the corresponding controls. Combined malignant and benign liver cell tumours were clearly increased in both sexes, and in males a positive significant trend was also noted for the occurrence of hepatocellular carcinomas. In males the incidence of Harderian gland tumours was also significantly greater in treated groups than in controls. Some other neoplasms, such as lung tumours in both sexes and Harderian gland tumours and lymphomas in females, occurred in greater numbers in the treated groups, although the differences were not statistically significant in comparison with the controls. In addition, the incidences and total numbers of malignant tumours were significantly increased in treated groups of both sexes, although the increases were not dose dependent. The results demonstrated that musk xylol is carcinogenic in B6C3F1 mice when given at dose levels of 0.075 or 0.15% in the diet for 80 wk. PMID- 2242834 TI - Meeting report: Bruce Ames lecture. PMID- 2242836 TI - Comment: chemical carcinogens and human cancer. PMID- 2242835 TI - The Sellafield leukaemia cluster: a milestone in the history of mutagenesis? PMID- 2242837 TI - [Drowning accidents in childhood]. AB - This is a report on five boys aged between 1 and 5 years who, after prolonged submersion in cold water, were treated at our department. On being taken out of the water, all the patients were clinically dead. After 1- to 3-hour successful cardiopulmonary resuscitation, with a rectal temperature of about 27 degrees C, they were rewarmed at a rate of 1 degree/hour. Two patients died within a few hours after the accident. One patient survived with an apallic syndrome, 2 children survived with no sequelae. In the event of a water-related accident associated with hypothermia, we consider suitable resuscitation to have preference over rewarming measures. The most important treatment guidelines and prognostic factors are discussed. PMID- 2242838 TI - [Focal liver lesions as incidental findings. 2: Diagnostic procedures in sonographically homogeneous echo-rich, echo-poor or inhomogeneous lesions]. AB - Hemangioma is one of the most common incidental findings in the ultrasonographic image. In 80% to 90% of the cases, the hemangioma presents as a homogeneous lesion in the US image. In asymptomatic patients and a lesion diameter of less than 2 cm, further clarification additional to ultrasonography is not necessary. Major differential diagnoses are focal nodular hyperplasia, metastasis, hepatocellular carcinoma and liver cell adenoma. With exceptions, the biological significance of echo-poor or inhomogeneous lesions cannot be established on the basis of the US image. In such cases, additional diagnostic procedures are required. PMID- 2242839 TI - [First aid in animal poisons. 1: poisoning due to mussel consumption]. PMID- 2242840 TI - [High-dosage oral magnesium therapy in arrhythmias. Results of an observational study in 1.160 patients with arrhythmia]. AB - In the treatment of cardiac arrhythmias of varying genesis, an "observational study" in 1,160 patients showed that a high-dose oral magnesium preparation (Magnesium-Diasporal N 300 Granulat) was effective. In 82% of the patients observed, a dose of at least 300 mg magnesium/day produced good to very good results. Adverse effects of the drug were observed in only 1.6% of the patients. For all groups, the "success parameters" improved significantly. High-rate arrhythmias showed a better response to magnesium treatment than did low-rate arrhythmias, with a close correlation being found with the heart rate at the start of treatment. High-dose oral magnesium had a positive effect on concomitant hypertension. At a dosage of 300 mg treatment should be continued for at least 6 weeks. PMID- 2242841 TI - [From Bergmanns' Hospital to university institution. Bergmannsheil Bochum- pathological institute]. PMID- 2242842 TI - [Trans-vaginal sonography in gynecological practice]. AB - Some 1,077 transvaginal ultrasonic studies performed in the gynecologist's office are reported. The US technique employed was particularly useful, since, in combination with the pelvic examination, it permitted rapid and accurate diagnosis. Patient acceptance was very high. Both in the gynecological and obstetric examinations, pathological findings were established in about 30% of the cases. In the diagnostic evaluation of both pre- and post-menopausal endometrium, and of the uterine cervix in advanced pregnancies, transvaginal ultrasonography opens up new diagnostic possibilities that can lead to a selective indication for D & C and cerclage. PMID- 2242843 TI - [A new tube for the endobronchial application of drugs]. AB - During cardiopulmonary resuscitation, endobronchial administration of epinephrine, atropine and lidocaine is required as the initial step. This procedure provides a decisive time advantage, since it can be effected before venous access is established. The presently available techniques (direct application, catheter insertion, etc.), however, have disadvantages (interruption of ventilation, difficult catheter placement, time loss). For this reason we have developed a tube for endobronchial drug and gas application during resuscitation (EDGAR tube). It enables direct injection into the bronchial system via a separate injection canal within the wall of the tube that terminates at the tip of the tube. In this way, simple and safe application of the drugs to the appropriate absorption surface is ensured, without any loss of time. In view of these significant advantages, the use of the EDGAR tube is recommended for intubation for resuscitation purposes. PMID- 2242844 TI - [Rapid progression of the AIDS epidemic in eastern Africa]. PMID- 2242845 TI - [First aid for animal poisons. 2: Poisoning due to fish consumption]. PMID- 2242846 TI - [Cerebral insufficiency--treatment with Ginkgo-biloba extract. Time of onset of effect in a double-blind study with 60 inpatients]. AB - Sixty inpatients with cerebral insufficiency and the leading symptom depressive mood, were treated in a double-blind study for 6 weeks with a daily dose of 160 mg Ginkgo biloba extract or placebo. After 2, 4 and 6 weeks, changes in 12 typical symptoms in comparison with the last examination, were evaluated. In the group receiving placebo, small, but progressive improvements were observed. In the Ginkgo-biloba group, the overall number of improvements was significantly larger. After 2 weeks the differences were marked for only a few of the symptoms; after 4 and 6 weeks in contrast, in 11 of the 12 symptoms. The largest number of improvements in the Ginkgo-biloba group was observed between the 2nd and 4th weeks of treatment. In this period, about two-thirds of the patients on Ginkgo biloba, and about one-fifth of the patients on placebo showed improvements. PMID- 2242847 TI - Viral myocarditis. AB - Evidence suggests that in susceptible individuals lymphocytic myocarditis is a virus-induced autoimmune disease which may progress to dilated cardiomyopathy. Its biopsy pathology, the application of the 'Dallas' criteria for diagnosis and the role of immunohistochemistry are discussed. The potential role for in situ hybridization in the detection of viral genomes is referred to. Pathogenesis may be related to persistence of viral RNA in tissues and may involve both cellular and humoral immune mechanisms. The effect may manifest itself at cellular level with myocytolysis or at sub-cellular level with interference in energy production, giving rise to considerable functional deficit with few morphological changes. PMID- 2242848 TI - Primary lymphoma of the thyroid: a clinical, histological and immunohistochemical study of 20 cases. AB - Twenty cases of malignant lymphoma arising in the thyroid gland were studied clinically, histologically and immunohistochemically. Nineteen cases were non Hodgkin's lymphoma (15 diffuse and four follicular lymphoma) and one was a plasmacytoma. Immunohistochemical analysis of the lymphomas using paraffin embedded sections disclosed that 17 lymphomas were B-cell type and two were T cell type. The plasmacytoma was of IgG kappa type. The large majority of the lymphomas were associated with an underlying chronic thyroiditis. The 5-year survival rate of the patients was 70%. An unfavourable diagnosis was more likely when the tumour was diffuse rather than follicular, when it was of diffuse large cell type or of immunoblastic type and when there was cervical lymph node involvement. PMID- 2242850 TI - A study of vesical adenocarcinoma, intestinal metaplasia and related lesions using mucin histochemistry. AB - Biopsy and autopsy material from the urinary bladder was studied using PAS and PAS-D techniques to identify glycogen and neutral mucins, the alcian blue/high iron diamine method to distinguish sialo- and sulphamucins and the PB/KOH/PAS technique to localize O-acylated sialomucins. All of 10 examples of normal urothelium and both of two cases of transitional carcinoma in situ contained glycogen, but no mucin. Other lesions displayed one of two patterns of mucin production: the extracellular mucin seen focally in 17 cases of cystitis cystica consisted of sialo- and/or neutral mucins only, a pattern also displayed by mucins produced in 10 of 13 examples of transitional cell carcinomas and by three of nine tumours purely or in part adenocarcinomas. The intracellular mucins expressed in five of the 17 cases of cystitis glandularis and in all of eight cases of frank intestinal metaplasia with goblet cells displayed a colonic phenotype, with production of O-acylated sialomucins. A similar profile was expressed by six adenocarcinomas and this included tumours likely to be of vesical and also of urachal origin. It is concluded that identification of O acylated mucins cannot distinguish between primary bladder tumours and metastases from a colonic primary, or between carcinomas of vesical and urachal origin. PMID- 2242849 TI - Mucin histochemistry and lectin binding sites in intestinal metaplasia of the urinary bladder. AB - We report a case of intestinal metaplasia of the bladder urothelium associated with dysplastic foci and a transitional cell carcinoma. A mixture of sialomucins, O-acetylated sialomucins and sulphomucins was found in the goblet cells. Neuraminidase resistant binding of the lectin peanut agglutinin was demonstrated in the brush border of columnar cells in intestinal metaplasia and diffusely in columnar cells in dysplastic foci. The histochemical findings are compared with those described in normal, dysplastic and neoplastic colonic mucosa. PMID- 2242851 TI - QBEND/10, a new monoclonal antibody to endothelium: assessment of its diagnostic utility in paraffin sections. AB - The immunoreactivity of a new monoclonal antibody to endothelium. QBEND/10, in formalin-fixed, paraffin-embedded sections from a variety of vascular and lymphatic tumours is described and compared to that of two other endothelial markers, von Willebrand factor and Ulex europaeus agglutinin, type 1. All the benign tumours of blood vascular origin showed immunoreactivity whereas only five out of eight lymphangiomas demonstrated a weak focal reaction with QBEND/10. Primitive lumina in epithelioid and spindle cell haemangioendotheliomas were highlighted in all the cases. Tumour cells in angiosarcoma forming vasoformative areas and solid areas showed immunopositivity to QBEND/10 in 17/23 and 13/24 cases respectively, and complementary immunoreactivity for von Willebrand factor was observed. Proliferating vessels and the majority of spindle cells in Kaposi's sarcoma were positive in all 40 cases. Only one of 54 cases of carcinoma showed luminal reaction to QBEND/10. However, 17 of 45 spindle cell tumours displayed a positive reaction. QBEND/10 is an additional marker for demonstrating endothelial differentiation and has some advantages over currently available antibodies. PMID- 2242853 TI - Extraskeletal mesenchymal chondrosarcoma of the mediastinum. AB - Extraskeletal mesenchymal chondrosarcoma is a rare tumour with a predilection for the meninges and lower limb, especially the thigh region. This paper reports an extraskeletal mesenchymal chondrosarcoma occurring in the posterior mediastinum, a previously undocumented site. PMID- 2242852 TI - Atypical stromal cells of lower female genital tract. AB - Atypical stromal cells were identified in either the cervix or vagina in 27 (13%) of 205 autopsy specimens. They were more commonly observed in the vulva, occurring in 29 (78.4%) of 37 vulvar surgical specimens. In only seven patients were the cells present as a continuous band; five in cervix or vagina and two in vulva. Electronmicroscopic examination confirmed the fibroblastic nature of these cells. Although hormonal influences may be responsible for this stromal alteration, their occurrence in elderly patients and in males at other sites is not consistent with a specific hormonal profile. It is important not to misdiagnose these cells as malignant. PMID- 2242854 TI - Post-radiation malignant peripheral nerve sheath tumour: a report of two cases. PMID- 2242855 TI - Granulomatous inflammation of the spleen in infectious mononucleosis. AB - Granulomatous inflammation of the spleen has not previously been recorded in infectious mononucleosis. We report two cases and describe further morphological features more often associated with malignant lymphoid conditions. PMID- 2242856 TI - Symmetrical fibro-osseous dysplasia of rib--evidence for a traumatic aetiology. PMID- 2242857 TI - Gamna-Gandy nodules in a cardiac myxoma. AB - A 33-year-old female was admitted for surgery for removal of a left atrial myxoma. Histological examination of the tumour showed features characteristic of myxoma. Additionally, Gamna-Gandy bodies were present in the tumour. This is a rare finding. PMID- 2242858 TI - The histological and immunohistochemical evidence of squamous metaplasia from the myoepithelial cells in the breast. AB - Squamous metaplasia in the breast is well documented. However, the putative cell of origin for the squamous epithelium is not clear. This paper describes a case of fibroadenoma of the breast with myoepithelial hyperplasia and squamous metaplasia. The histological finding of transition between myoepithelial cells and squamous cells and the immunohistochemical expressions of actin and S-100 in the metaplastic squamous cells support the myoepithelial origin of squamous epithelium in the breast. PMID- 2242859 TI - Capillaria hepatica infestation in a 2-year-old girl. PMID- 2242860 TI - Before our time: half a century of histiocytic medullary reticulosis: a T-cell teaser? PMID- 2242861 TI - 'Skip lesions' in ulcerative colitis. PMID- 2242862 TI - Monocytoid B-cell lymphoma--a MALT tumour? PMID- 2242863 TI - Who was Sago? PMID- 2242864 TI - The benefits and drawbacks of managed care. PMID- 2242865 TI - Voluntary hospitalization and due process: the dilemma of Zinermon v. Burch. PMID- 2242866 TI - Implications of managed care for social work in psychiatric hospitals. PMID- 2242867 TI - Are England's psychiatric services for schizophrenia improving? PMID- 2242868 TI - Managed mental health care: myths and realities in the 1990s. AB - Managed care may be viewed as the most recent attempt to control the rate of increase of health and mental health care costs in the United States. The majority of people who receive insured mental health services do so through some form of managed care program. Now increasing concerns are being raised about whether managed care really reduces costs, whether it adversely affects the quality of care, and whether it restricts access to care. The author discusses the origins, actors, and major issues involved in managed health care in terms of prevailing myths and future realities. He calls for more and better research to answer important clinical and policy questions about managed care and for improved communication between mental health professionals and managed care organizations. PMID- 2242869 TI - Managed care: an approach to rational psychiatric treatment. AB - The author argues that rational mental health care delivery is possible through an appropriate managed care system of independent providers. The right model for delivery of care incorporates principles that include rational assignment of clinical functions, epidemiologic accountability, fiscal as well as clinical responsibility, open and direct patient access, incentives for preventive psychiatry, partnership between management and clinical providers, choice of services, outcome assessment, and interface between public and private providers. The author maintains that a link between what is good about private practice and what is good in rational managed care represents the best mental health care delivery system currently available. PMID- 2242870 TI - Managed care: a means of rationing psychiatric treatment. AB - Some form of patient care review has become an integral component of most health insurance plans. The author describes the numerous ways in which such review negatively affects the therapeutic relationship between the doctor and the patient. Pressured to cut costs, reviewers are unlikely to be objective in their evaluation of the need for treatment. Many are not qualified to review particular types of treatment. Avenues for appeal of reviewers' decisions are weak. The intensity and frequency of review are often disruptive both to the treatment and to the psychiatrist's practice. Some patients discontinue treatment after learning that their care is being reviewed because of fears about loss of confidentiality or other reasons. Informed consent procedures relating to release and protection of confidential information are inadequate. The author emphasizes the need for setting standards for review organizations that will help overcome these and other problems. PMID- 2242872 TI - Developing practice parameters: an interview with John McIntyre. Interview by John A. Talbott. PMID- 2242871 TI - Utilization management and the quality of care. AB - Utilization management is a mechanism for managing health care costs by assessing the appropriateness of care and influencing decisions about its provision to ensure the least costly but most effective treatment. Thus while primarily focused on reducing costs, utilization management also affects quality of care. The author reviews the historical development of utilization management, summarizes the review procedure, and suggests ways to enhance understanding of the effect of utilization management on quality of care. PMID- 2242874 TI - Characteristics of repeatedly assaultive psychiatric inpatients. AB - Investigations of assaults in psychiatric hospitals have found that a small proportion of inpatients are responsible for a large percentage of the violence that occurs. In a large state hospital patients who were repeatedly violent (recidivists) were compared with patients who were violent only once or twice (nonrecidivists), and the relationships between repeatedly violent behavior and gender, age, and diagnosis were examined. All reports of violent incidents over a six-month period for a population of 1,552 inpatients--a total of 497 incidents involving 313 patients--were reviewed. Seventy patients were involved in three or more incidents each and were responsible for 53 percent of all violence. Recidivist men inflicted serious injuries at a rate ten times higher than that for all the other violent patients. Recidivist women were significantly younger than nonrecidivist assaultive women and were about the same mean age as the assaultive men. Recidivist women were also more likely to have organic brain disorder or personality disorder. PMID- 2242875 TI - Gold Award. A public-private alliance to meet the needs of chronic mentally ill patients. Extended Care Program, West Central Human Service Center, North Dakota Department of Human Services, Bismarck. PMID- 2242873 TI - Treatment of depressed patients in general hospitals with scatter beds, cluster beds, and psychiatric units. AB - Records of 725 patients with a primary discharge diagnosis of depression were reviewed at nine general hospitals: three with psychiatric units, three in which patients were treated in beds grouped together on a medical or surgical floor (cluster beds), and three in which patients were treated in beds dispersed among medical and surgical beds (scatter beds). Patients treated in psychiatric units most commonly presented with suicidal or homicidal indicators, most frequently received antidepressants, and had the longest stays. Patients treated in scatter beds tended to present with somatic complaints, were least likely to receive antidepressants, and had the shortest hospital stays. Patients treated in cluster beds presented with intermediate symptoms and had stays of intermediate duration. Although dangerous or psychotic patients may be most appropriately treated in units, other patient groups may be safely and effectively treated at lower cost in less specialized inpatient settings. PMID- 2242876 TI - Gold Award. A multifaceted program for preventing and treating eating disorders. Programme for Eating Disorders, Department of Psychiatry, The Toronto Hospital, University of Toronto. PMID- 2242877 TI - Significant Achievement Awards. Treating the effects of trauma among Southeast Asian refugees--Indochinese Psychiatry Clinic, Department of Psychiatry, St. Elizabeth's Hospital, Boston. PMID- 2242878 TI - Significant achievement awards. Comprehensive mental health services for elderly citizens--Positive Aging Services, Massachusetts Mental Health Center, Boston. PMID- 2242880 TI - Significant Achievement Awards. Promoting renewed interest in ECT treatment, education and research--Electroconvulsive Therapy Program, Department of Psychiatry, University of Michigan Medical Center, Ann Arbor, Michigan. PMID- 2242879 TI - Significant Achievement Awards. A mental health program for juvenile offenders in state training school--Hawthorn Center Clinic for Adjudicated Youth, Northville, Michigan. PMID- 2242881 TI - Significant Achievement Awards. Patients helping themselves by helping the homeless--Share Your Bounty, the Friends of the Homeless Project, Bronx Psychiatric Center, Bronx, New York. PMID- 2242882 TI - Substance abuse and psychiatric disorders in prison inmates. PMID- 2242883 TI - Barriers to community treatment of patients with dual diagnoses. PMID- 2242884 TI - A process for do-not-resuscitate decisions in psychiatric hospitals. PMID- 2242885 TI - A model for successful job placement of residents in small board-and-care facilities. PMID- 2242886 TI - Psychiatric evaluation of competency in physically ill patients who refuse treatment. PMID- 2242887 TI - Reducing staff injuries. PMID- 2242889 TI - Britain's path. PMID- 2242888 TI - HIV positivity in inmates. PMID- 2242890 TI - Data watch. How many uninsured Americans are there? PMID- 2242891 TI - The new hospital CEO: many paths to the top. AB - A new kind of hospital CEO is beginning to emerge--one who has superior qualifications in a number of areas, including financial, operational, and interpersonal skills. As the position continues to evolve, its candidate requirements are shifting. The "traditional" hospital CEO, who advanced through mainly operations positions, is still in high demand and considered by many to be well prepared to meet current hospital challenges. But the emergence of chief executives from "alternative" backgrounds signals a new diversification in the field. We surveyed 556 hospital CEOs throughout the United States to get their views on selection, and we spoke with experts and leaders in the field with broadly divergent views. Who's on the inside track? The answers may surprise you. PMID- 2242892 TI - Experts offer differing views on the impact of a recession. AB - What are the risks of a prolonged recession for hospitals? Although health care would probably not be hurt as much as other industries by a lengthy downturn, financial experts are saying a continuation of the current soft economy would add to hospitals' already long list of financial woes. The coming recession "will exacerbate the problems for hospitals already facing fiscal stress," says Glenn Wagner, an investment banking consultant based in New York City. PMID- 2242893 TI - Lawsuits can pave rocky road to adequate Medicaid payment. AB - Wilder et al v. The Virginia Hospital Association is about to go to trial. Wilder is the case that resulted in the Supreme Court's June ruling affirming hospitals' right to sue state governments for inadequate Medicaid reimbursement. A federal court in Richmond must now decide whether Virginia's payment plan adequately reimburses the state's hospitals. And with momentum of their own, individual hospitals and state hospital associations are pressing hard for fair Medicaid reimbursements. PMID- 2242894 TI - Case study: quality improvement in a diversified health center. AB - Hospitals are beginning to apply industry models of quality improvement to their own, very different, health care settings, and some are achieving note-worthy success. Rush-Presbyterian-St. Luke's Medical Center, Chicago, is implementing the total quality management process originally developed by Minnesota Mining and Manufacturing (3M) Co., St. Paul. PMID- 2242895 TI - Managed care exec bridges gap between hospitals, employers. AB - An employer advocate can also be sensitive to provider needs, says Marsha Ballard. As CEO of Parkside Health Management Corp., Park Ridge, IL, Ballard develops managed care products that meet specific employer needs. Sensitivity to both providers and employers is crucial to Parkside's new national transplant network, she says. PMID- 2242897 TI - CEOs: Gulf crisis hits hospitals' bottom line. AB - Hospital CEOs say the Persian Gulf crisis could hit them hard where it counts. In fact, hospitals are already seeing some adverse impact from events in the Middle East. From fundraising to plant management to strategic planning, the confrontations in the Gulf are having an impact on the hospital's bottom line. PMID- 2242896 TI - Total quality management: steps to success. PMID- 2242898 TI - HDS (Health Data Sciences) enters patient care info systems market. PMID- 2242899 TI - Hospital to HMO: we don't need your business. PMID- 2242901 TI - AMA offers new service to simplify credentialing. PMID- 2242900 TI - Congress postpones HCFA's outpatient pay reform plan. PMID- 2242902 TI - Alzheimer's care: need outweighs financial risk. PMID- 2242903 TI - Homes doubt they can computerize per HCFA's request. PMID- 2242904 TI - Are some HIS (hospital information systems) alliances unfair to hospitals? PMID- 2242905 TI - Hospitals should pursue employer contracts. PMID- 2242907 TI - A brief history of injury. PMID- 2242908 TI - The art and science of editing. PMID- 2242906 TI - Rapid HLA-DPB typing using enzymatically amplified DNA and nonradioactive sequence-specific oligonucleotide probes. AB - A simple and rapid method for characterizing the polymorphism at the HLA-DPB1 locus has been developed. The procedure involves the selective amplification of the polymorphic second exon of the DPB1 locus by the polymerase chain reaction (PCR), followed by hybridization of the amplified DNA with 15 nonisotopic sequence-specific oligonucleotide probes. There are no sequences within the second exon of the DPB1 locus that uniquely define an allele; rather, each allele appears to arise from the shuffling of a limited number of polymorphic nucleotide sequences in six regions of variability. Consequently, individual alleles are identified by the pattern of hybridization of the 15 probes. Two formats for typing are described. In Format I (the dot-blot), the amplified DNA is ultraviolet (UV) cross-linked to a nylon membrane and hybridized with the oligonucleotide probes which are covalently labeled with horseradish peroxidase (HRP). In Format II (the reverse dot-blot), the oligonucleotides, which have poly T tails, are bound to the membrane and the immobilized array of probes is hybridized to the PCR product which has incorporated biotinylated primers during the amplification process. In both formats, hybridization is detected by a simple colorimetric reaction. The application of this technology to the fields of tissue typing and individual identity is discussed. PMID- 2242909 TI - Military surgery. PMID- 2242910 TI - Supracondylar fractures of the femur. PMID- 2242911 TI - Arthroscopy. PMID- 2242913 TI - Injured ligaments of the knee. PMID- 2242912 TI - AO fixation. PMID- 2242914 TI - Traumatic perforation of the bowel. PMID- 2242915 TI - Thoracolumbar spinal injuries. PMID- 2242916 TI - Nerve injury. PMID- 2242917 TI - Preventing secondary brain damage after head injury: a multidisciplinary challenge. PMID- 2242918 TI - Skin loss of the lower limb. PMID- 2242920 TI - A review of parachuting injuries. PMID- 2242919 TI - Sports injuries. PMID- 2242921 TI - Resuscitation. PMID- 2242923 TI - Forensic medicine. PMID- 2242922 TI - Litigation in trauma. PMID- 2242924 TI - Management of disordered growth following physeal injury. PMID- 2242925 TI - Presence of IgA and IgG antigliadin antibodies in healthy adults as measured by micro-ELISA. Effect of various cutoff levels on specificity and sensitivity when diagnosing coeliac disease. AB - In this study a micro-ELISA (ELISA = enzyme-linked immunosorbent assay) was established and used to evaluate IgA and IgG antigliadin antibodies in 1,866 healthy adults. There was a covariation between the level of IgA antigliadin antibodies and the total serum IgA concentration, probably due to an increased IgA response in some healthy subjects. We could not find any correlation between the presence of IgG and IgA antibodies in the healthy population using the 97.5th percentile as a cutoff value. The specificity of various cutoff levels was compared with the sensitivity of the test in a population of 40 patients with coeliac disease. IgA antigliadin antibodies had a high specificity (95%) at a cutoff value giving a high sensitivity (80%). This was not possible with IgG antigliadin antibodies which had a low sensitivity (40%) when the cutoff value was selected to give a high specificity. Due to the low prevalence of coeliac disease, a decrease in the specificity of the test will have a pronounced effect on the positive predictive value. The results indicate that only IgA antigliadin antibodies are useful markers when screening subjects with few typical symptoms for biopsy when diagnosing coeliac disease, whereas IgG antibodies are of low value because of their low specificity. PMID- 2242926 TI - Endotoxin-induced auto-immunity in mice. III. Comparison of different endotoxin preparations. AB - Six different endotoxin preparations derived from Escherichia coli and Salmonella typhimurium subspecies were compared as to their potencies to provoke auto-immune phenomena in mice. The numbers of spleen cells forming antibodies to bromelain treated isologous erythrocytes or anti-DNA antibodies, the serum levels of these auto-antibodies, and the circulating immune complex titres were determined. As far as comparison on a weight base was concerned, S. typhimurium Re-mutant lipopolysaccharide appeared to be the most active preparation in inducing auto antibody formation. Upon comparison of amounts with equal activity in the limulus amoebocyte lysate assay, however, S. typhimurium lipid A turned out to be the most potent. The contribution of O-type specific polysaccharides, phosphate groups, and the lipid A moiety to the potencies of the endotoxin preparations is discussed. PMID- 2242927 TI - Human IgE, IgG and IgA antibody responses to T101, a murine monoclonal antibody against human lymphocytes: implications for pathogenesis, risk and avoidance of adverse immunologic reactions. AB - To study immune responses that may play a role in immediate-type allergic reactions (ITAR) and serum-sickness-like reactions that have been reported with administration of monoclonal antibodies (MAb), we measured by enzyme-linked immunosorbent assay serum levels of IgE, IgG, and IgA human antimurine antibody (HAMA) to T101, a murine IgG2a antibody that has been used in the treatment of cutaneous T cell lymphoma (CTCL) and chronic lymphocytic leukemia (CLL). None of 8 patients (4 with CLL, 4 CTCL) pretreated with T101 had elevated titers of any HAMA class tested as compared to normal control sera. All CTCL patients who had elevated total serum IgE levels, but normal total serum levels of other antibody classes, had significant rises in IgE, IgG, and IgA HAMA to T101 after intravenous MAb infusion. However, the CLL patients who were hypogammaglobulinemic failed to develop significant rises in HAMA. Three patients (2 CLL, 1 CTCL) had ITAR (e.g., urticaria, angioedema, bronchospasm) associated with infusion of T101; prophylactic medication regimens based upon the control of radiographic contrast media reactions were used with apparent benefit in subsequent infusions in these patients. All 8 patients had negative immediate intradermal skin tests (1 microgram/ml) to T101 prior to its infusion. Our data confirm that (1) non-IgE-mediated mechanisms cause ITAR from this MAb, possibly by a mechanism inherent in the action of this MAb against lymphocytes, and (2) that isotypic antibody responses to MAb vary with the type of malignancy being treated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242928 TI - Bronchial responsiveness to mite allergen in atopic dermatitis without asthma. AB - Eight patients with atopic dermatitis (AD) without a history of asthmatic episodes and 8 patients with mite-allergic bronchial asthma (BA) were subjected to bronchial inhalation challenge with a nonspecific stimulus (acetylcholine) and an immunologically specific stimulus (house dust mite allergen). AD patients had a significantly greater concentration of IgE (p less than 0.01) and antimite IgE antibody (p less than 0.05) than BA patients. Nonspecific bronchial hyperreactivities of AD patients distributed from normal to asthmatic range. After allergen challenge, all 8 AD patients and all 8 BA patients showed an immediate asthmatic response (IAR). The mite extract concentration to induce an IAR was significantly (p less than 0.01) greater in AD patients than in BA patients. A late asthmatic response was observed in 6 out of 8 BA patients, whereas it was not observed in any AD patient. Our results showed that AD patients are less reactive to a specific mite allergen than BA patients in spite of greater concentrations of antimite IgE antibody. They suggest that this difference in the bronchial reactivity to the allergen concerns the difference in the onset of clinical symptoms and that a certain level of bronchial hyperreactivity to the allergen is a prerequisite for the development of asthmatic symptoms. PMID- 2242929 TI - Shared allergenic activity in Asian (Blattella asahinai), German (Blattella germanica), American (Periplaneta americana), and Oriental (Blatta orientalis) cockroach species. AB - Whole-body extracts of the feral and peridomestic Asian cockroach (Blattella asahinai) and the three domestic cockroach species, German (Blattella germanica), American (Periplaneta americana), and Oriental (Blatta orientalis), were compared allergenically using an IgE serum pool from 4 German cockroach sensitive individuals. In crossover radioallergosorbent inhibition analysis, the Asian cockroach shared allergenic activity primarily with the German cockroach polymer and to a lesser extent with either the American or Oriental cockroach polymers. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and thin layer isoelectric focusing analysis of the extracts showed similar although varying intensities of Coomassie blue stained banding patterns among five extracts analyzed. Electroblotting analysis with 12.5% SDS-PAGE of the whole-body German cockroach extract and IgE serum from individuals sensitive to German cockroach revealed eight allergenic components with apparent molecular weights of 92, 80, 67, 48, 36, 27, 25 and 18 kD. Five components could be identified in the whole-body extract of the Asian cockroach corresponding to apparent molecular weights of 92, 67, 48, 40, and 32 kD. Analysis of individual serum by immunoblot analysis with each of the cockroach extracts showed considerable heterogenicity in the IgE-binding pattern. Although the Asian cockroach demonstrated considerable cross-reacting allergenic components to German and relatively fewer cross-reacting allergenic components to either the Oriental or American, it is too early to establish genus- or species-specific cockroach allergens. It is important to point out that German cockroach sensitive individuals should be made aware of the potential exposure of Asian cockroach aeroallergens both indoors and outdoors in areas with high infestations of Asian cockroaches. PMID- 2242930 TI - Characteristics of MTT as an indicator of viability and respiratory burst activity of human neutrophils. AB - In the present study, we have examined the suitability of 3-[4,5-dimethylthiazol 2-yl]-2,5-diphenyltetrazolium bromide (MTT) for assessing the viability and respiratory burst activity of human neutrophils. MTT is a good indicator of the relative viability of neutrophils which have been in culture up to 24 h, if sufficient serum (10% fetal calf serum) is present in the medium and the cells being compared have been in culture for a similar period of time. However, it is not suitable for exact assessment of percent viable cells in a cell population with low viability. The effectiveness of MTT as an indicator of respiratory burst activity is demonstrated by the sharp increase in MTT reduction induced by respiratory burst stimuli and by the ability of superoxide dismutase to inhibit 75% of MTT reduction by stimulated neutrophils. Unlike nitroblue tetrazolium (which is reduced primarily intracellularly) and cytochrome c (which is reduced extracellularly), MTT is apparently reduced both intracellulary and extracellulary by activated neutrophils. PMID- 2242931 TI - Identification of soybean allergens by immunoblotting with sera from soy-allergic adults. AB - Immunoblots were used to compare the IgE-binding proteins of various soybean products using sera from 7 soybean-allergic patients. Blotting results indicate at least two distinct individualistic patterns of IgE binding to soy proteins. Serum IgE from individuals allergic to both peanuts and soybeans binds to several proteins with molecular weights ranging from 50,000 to 60,000 daltons, while IgE from individuals allergic to soybeans, but not peanuts, binds strongly to a protein(s) with a molecular weight of 20,000 daltons. The soy products tested displayed varying amounts of IgE binding with sera from sensitive patients. PMID- 2242932 TI - Elevation of neutrophil chemotactic activity in the human serum and the decreased number of neutrophils after platelet-activating factor inhalation. AB - We previously reported a significant decrease in neutrophils at 5 min and an increased number of neutrophils at 15 min after PAF-acether inhalation. To investigate the mechanism, we measured the neutrophil chemotactic activity of the sera. Neutrophil chemotactic activity (NCA) of the serum at 5 min was greater than at baseline (p less than 0.01) or at 15 min (p less than 0.05). Furthermore, we investigated the correlation between the change in NCA and decreased number of neutrophils. A significant correlation was found between these two at 5 min (r = 0.751, p less than 0.05). These data suggest that an elevation of NCA may play an important role in the decrease of circulating neutrophils after PAF-acether inhalation. PMID- 2242933 TI - Corneal modeling as an aid to radial keratotomy. PMID- 2242934 TI - Mathematical model for the computation of alveolar partial pressure of carbon monoxide. AB - A mathematical model is formulated for computing alveolar partial pressure of carbon monoxide (PACO) from that in the atmospheric air. The model takes into account parameters like inspired/expired air flow rates, diffusion capacity of the lung, concentration of CO in the atmospheric air, blood flow rate and the non linear CO dissociation curve. The effect due to the presence of O2 in the blood on CO dissociation curve is also incorporated. It is shown that for a given atmospheric CO concentration, PACO increases exponentialy with time and attains asymptotic value. Alveolar PCO increases further with the increase in the atmospheric CO concentration. The model can also be used to compute carboxyhaemoglobin levels in the blood as a function of exposure time and the results are comparable with the CFK equation and the values measured experimentally. PMID- 2242935 TI - Simulating functional interactions in the brain: a model for examining correlations between regional cerebral metabolic rates. AB - A computer simulation model was developed to investigate the use of interregional correlations of cerebral metabolic rates to analyze functional interactions in the brain. The model generates simulated metabolic data for individual brain regions in a specified number of subjects, where there are defined functional couplings amongst the regions. Random numbers provide the variability seen in measured metabolic data. Correlational analysis is performed on these simulated data sets. The parameters of the model can be chosen so that simulated and actual metabolic data are very similar. The model demonstrates that the change in the correlation coefficient between normalized metabolic data in two brain regions is related to the change in the strength of the functional association between the two regions. The model also is used to explore the relations between patterns of correlations and the underlying sets of functional couplings. The results indicate that correlational analysis provides more information about regional involvement in neural systems than does region-by-region comparisons of absolute metabolic rates. PMID- 2242936 TI - Computer-aided decision support in acute abdominal pain, with special reference to the EC concerted action. AB - This presentation describes the use of computer aided decision support in acute abdominal pain. The need for such support is explored and the feasability of providing support is described with reference to studies involving nearly 100,000 patients. It is argued that the provision of computer aided decision support can lead to substantial and practical benefit in clinical care--but this is mostly due to the constant stimulus towards "doing it right". This in turn depends upon the provision of a consensus view of "good medicine" in the area concerned; and on an international level strongly argues the case for multi-national cooperative studies to define good medicine and make it available. One such study (the European Community Concerted Action on Acute Abdominal Pain) is described. PMID- 2242937 TI - Application of artificial intelligence techniques to a well defined clinical problem: jaundice diagnosis. AB - Jaundice is a very common medical condition, in which pathophysiological knowledge has been quite well assessed and clinical features are usually well known. However, incorrect conclusions are sometimes reached in medical practice which can lead to serious implications. Thus, jaundice diagnosis appears as one of the medical situations which might be substantially improved by computer assistance. The present study is aimed at describing and discussing in what way a computer program supporting medical decision making in jaundiced patients can be developed on the basis of advanced Artificial Intelligence methods. To this extent methodological problems concerned with the organization and the formalization of medical knowledge have been outlined with some detail. The resulting expert system is expected to become a well assessed and potentially useful tool for both medical decision making and medical education. PMID- 2242938 TI - Teaching field potentials: a microcomputer simulation of the nerve action potential in a bidimensional conductor. AB - A computer simulation of the extracellular field potential recording of nerve activity is presented. An experimental setup composed of an oscilloscope, a nerve, a conductive surface, and a recording electrode is graphically simulated. The user may study the influence of the position of the recording electrode and of certain nerve properties (membrane potential, velocity of conduction and action potential duration), on the action potential shape. The different waves which constitute the action potential may be analyzed and their peak values plotted as a function of the independent variable (e.g. electrode distance from the nerve). Three-dimensional plots of a set of action potentials as a function of the independent variable may also be obtained. The stimulation allows the user to study the basic factors which determine the configuration of an extracellularly recorded compound nerve action potential. PMID- 2242939 TI - Leukonychia. Review and classification. PMID- 2242940 TI - Treatment of subacute cutaneous lupus erythematosus. PMID- 2242941 TI - The reconstruction of skin. How and why. PMID- 2242942 TI - Patterns of directional growth in the epidermis. PMID- 2242943 TI - Acne keloidalis-like lesions on the scalp associated with antiepileptic drugs. AB - A man developed acne keloidalis-like lesions in the scalp during treatment with diphenylhydantoin and carbamazepine for epilepsy. These drugs were suspected to play a role in the pathogenesis of this skin disease in an unusual location, based on clinical evidence and on the in vitro test, mast cell degranulation (MCD). PMID- 2242944 TI - Clinicopathologic study of cutaneous plasmacytoma. AB - Eight patients with skin tumor lesions composed of dense, predominantly plasma cell infiltrates were studied. Primary cutaneous plasmacytoma can be reactive (polyclonal) or neoplastic (monoclonal). In four of the patients skin lesions were associated with multiple myeloma. Specific skin lesions usually consisted of reddish or purple nodules located on the trunk. In one case the cutaneous lesions developed at the site of previous herpes zoster. Histologically, the cutaneous plasmacytic infiltrate was mainly diffuse and monomorphous. Most of the plasma cells were mature, but in some cases immature immunoblasts and mitoses were observed. Serum immunoelectrophoresis findings correlated with the monoclonality or polyclonality of the plasmacytoma. Presence or absence of systemic involvement cannot be predicted from the appearance of clinical lesions or from maturity of plasma cell infiltration in the skin. PMID- 2242945 TI - Erythromelalgia. AB - Erythromelalgia, characterized by temperature-dependent redness, pain, and warmth in one or more extremities, may be a primary disease or occur secondarily to underlying illnesses. Myeloproliferative disorders (eg, essential thrombocythemia) and a number of other associations have been reported. Two cases are described: one associated with essential thrombocythemia and the other the first reported case associated with pernicious anemia. PMID- 2242946 TI - Malignant syphilis in HIV-infected patients. PMID- 2242947 TI - Staphylococcus aureus in atopic dermatitis and in nonatopic dermatitis. AB - Skin colonization with Staphylococcus aureus (S. aureus) was examined in 30 patients with atopic dermatitis (AD), in 25 patients with nonatopic eczema (NAE) and in 30 individuals as healthy controls (HC). Bacteria growth was examined in aerobic cultures and the population densities per dish were estimated; S. aureus colonization was found in the eczematous skin of 24 of 30 (80%) AD patients and in 13 of 25 (52%) NAE patients (NS, p greater than 0.1). In nonaffected skin S. aureus colonization was found in 19 of 30 (63%) of all AD patients compared with 6 of 25 (24%) in NAE patients and 1 of 30 (3%) in HC, respectively (p less than 0.05). In nonaffected skin, coagulase negative strains of staphylococcus were found in 25 of 30 (84%) controls and in 18 of 25 (72%) NAE patients compared with 12 of 30 (40%) patients with AD. It seems that colonization with S. aureus is not a characteristic feature for atopic dermatitis but is a frequent event in damaged skin; significantly elevated values were also observed in nonatopic eczema. The degree of colonization may depend on the severity and duration of the eczematous lesions. PMID- 2242948 TI - Malignant melanoma in a speckled zosteriform lentiginous nevus. PMID- 2242949 TI - Ulcerative secondary syphilis. PMID- 2242950 TI - Subacute cutaneous lupus erythematosus response to isotretinoin. PMID- 2242951 TI - The role of fish oil in psoriasis. A randomized, double-blind, placebo-controlled study to evaluate the effect of fish oil and topical corticosteroid therapy in psoriasis. AB - In a randomized, double-blind, placebo-controlled study, patients received 10 fish or olive oil capsules three times daily for the whole study in addition to applying betamethasone diproprionate to their psoriatic plaques for the first 3 weeks. Most patients gradually worsened upon discontinuation of corticosteroids. Using survival analysis methods, no significant difference was found between the fish and olive oil groups. The authors attempt to put the role of fish oil in the therapy of psoriasis into perspective and discuss the efficacy of fish oil when used alone versus in combination therapy. PMID- 2242952 TI - Requiem for smallpox. The demise of a disease. PMID- 2242953 TI - Intradermal immunotherapy in children with severe skin inflammatory reactions to Aedes aegypti and Culex quinquefasciatus mosquito bites. PMID- 2242954 TI - Points in question. PMID- 2242955 TI - Points in question. Genetic diversity in Echinococcus granulosus. PMID- 2242956 TI - Antibody-mediated cytotoxic effects in vitro and in vivo of rat cells on infective larvae of Brugia malayi. AB - Albino rat macrophages and neutrophils in the presence of immune serum adhered to and promoted killing of Brugia malayi infective larvae in vitro. At a similar cell-target ratio, macrophages were more potent than neutrophils in inducing cytotoxic response to the larvae. Eosinophils were also effective in killing but only at a high cell-target ratio. The activity in the immune serum could be absorbed to and eluted from a Protein A-Sepharose column suggesting involvement of IgG antibody in the reaction. An indirect fluorescent antibody test confirmed the presence of IgG on the surface of larvae incubated in immune serum. Infective larvae were attacked by host cells within micropore chambers 16-24 h after implantation into immunized rats. Further, a strong cytotoxic response to the larvae was seen when they were introduced intraperitoneally into immune rats indicating the role of antibody and cells in vivo. We suggest that antibody dependent cellular cytotoxicity may represent an important mechanism of parasite killing in an immune host. PMID- 2242957 TI - Isoparorchis hypselobagri: ultrastructure of the tegument and associated tissues in a digenean inhabiting a gaseous aerobic environment. AB - Adult I. hypselobagri live in the swim bladder of the Indian catfish Wallago attu, a gaseous environment with a relatively high oxygen content. The ventral tegument, which in life is applied close to the swim bladder wall, is relatively unspecialized, showing typical ultrastructural features of the digenean surface. The dorsal tegument, which is exposed to the oxygen-rich surroundings, has numerous pyriform extensions of superficial parenchymal cells closely applied to the base of the surface syncytium. These extensions bear numerous mitochondria and send finger-like processes deep into the basal cytoplasm of the syncytium where they interdigitate with corresponding infolds of the basal tegument membrane. The pyriform parenchymal extensions are connected with underlying nucleated cell bodies via irregular glycogen-filled tubular processes, many of which end blindly in the interstitial tissue or expand into glycogen-filled bulbs beneath the cell bodies. These superficial parenchymal processes associate at gap junctions with ramifications of a distinct deeper parenchymal tissue which contains lipid, residual bodies and glycogen. The dorsal tegument and associated structures may constitute a respiratory organ, taking advantage of molecular oxygen diffusing across the surface syncytium to carry out aerobic energy transduction in the superficial parenchymal extensions. ATP so generated may diffuse inwards for distribution throughout the body in the deep parenchymal tissue. The extensive network of ramifying cytoplasmic tubules is supported by a fibrous matrix of interstitial tissue. PMID- 2242958 TI - Population dynamics of Enterogyrus cichlidarum (Monogenea: Ancyrocephalinae) from the stomach of Tilapia spp. in Egypt. AB - In a 1-year seasonal study of the numbers of the stomach-inhabiting monogenean Enterogyrus cichlidarum in Tilapia nilotica in the River Nile, Egypt, prevalence and intensity reached a height in spring and infection levels were surprisingly high in winter. T. zillii harboured fewer parasites but seasonal changes were similar. No parasites were found in T. galilaea. The prevalence and intensity of the infection with E. cichlidarum rose significantly with increasing size of the host. Some of the possible reasons for these fluctuations are discussed. Immature enterogyrids were more abundant in the posterior sector of the stomach and adult enterogyrids showed a preference for the anterior sector. No significant difference was found in the numbers of enterogyrids in male and female hosts. PMID- 2242959 TI - Spermiogenesis and sperm ultrastructure in the monogenean parasite Acanthocotyle lobianchi. AB - The ultrastructural events of spermiogenesis and the ultrastructure of the mature spermatozoon of an acanthocotylid monogenean, Acanthocotyle lobianchi, are described. The early zone of differentiation (ZD) contains two roughly perpendicular centrioles which become parallel and produce two free flagella, although these later become incorporated into the same body of cytoplasm. No cortical microtubules were found supporting the ZD at any stage of spermiogenesis. Much of the length of the thread-like sperm contains two axonemes of the 9 + '1' pattern together with a nuclear and mitochondrial profile but the 'posterior' region is occupied only by a single axoneme and the nucleus. A laterally situated electron-lucent vesicle with specialization of the adjacent surface membrane is found in the 'anterior' region of the sperm. The phylogenetic implications of these observations are discussed. PMID- 2242960 TI - Three new species of Monocotyle (Monogenea: Monocotylidae) from the stingray, Himantura uarnak (Rajiformes: Dasyatidae) from the Great Barrier Reef: phylogenetic reconstruction, systematics and emended diagnoses. AB - Three new species of Monocotyle were found on the gills of the coachwhip stingray, Himantura uarnak (Rajiformes: Dasyatidae) collected at Heron Island, Great Barrier Reef, Australia (23 degrees 27' S, 151 degrees 55 'E). Monocotyle helicophallus new species, Monocotyle multiparous new species and Monocotyle spiremae new species all have a single testis and are distinguished from other described Monocotyle species by size of body and hamulus and number of coils of the sclerotized male copulatory organ (21-22, three to four and 29-42, respectively). Monocotyle helicophallus new species is characterized by several muscular genital papillae, one of which is traversed by the ejaculatory duct; M. spiremae new species is distinguished by a sclerotized accessory structure associated with the distal end of the male copulatory organ, a vaginal sclerite and a conspicuous spherical, ejaculatory bulb; M. multiparous new species is distinguished by a large number of retained, thin-shelled eggs, many of which contain a fully developed oncomiracidium. A phylogenetic analysis of the 14 described species of Monocotyle utilizing 13 characters (11 binary and two multistate) produced the most parsimonious cladogram involving 18 steps with a consistency index of 0.78, two homoplasies and four unresolved polychotomies. Emended diagnoses of the Monocotylinae and Monocotyle are provided. PMID- 2242961 TI - The subcutaneous attachment of the monogenean Heterobothrium elongatum (Diclidophoridae) in the gills of Torquigener pleurogramma (Pisces: Tetraodontidae). AB - Heterobothrium elongatum predominantly occurred on the most anterior pair of gill arches of infected pufferfish, Torquigener pleurogramma. Juvenile and immature stages attached to gill lamellae and were concentrated on the ventral regions of the anterior pair of gill arches. Following penetration of subcutaneous tissues, young adult worms formed a subcutaneous channel either directly above or below the transverse septum, a tissue layer connecting the bases of adjacent gill rays. Large, sexually mature worms extended for most or all of the length of the gill arch where they filled the area normally occupied by the longitudinal lymphatic vessel (branchial vein) or lay adjacent to the efferent branchial and colateral arteries. Subcutaneous attachment by the parasite induced a marked inflammatory reaction in the host. During growth, the mid-region of the parasite became markedly elongate and formed a stalk connecting the haptor lying in the dorsal region of the gill and the body which emerged from the lower margin of the gill where penetration began. PMID- 2242962 TI - Introduction of a Brachylaima species (Digenea: Brachylaimidae) to Australia. AB - A Brachylaima species recorded previously from the house mouse (Mus domesticus) in South Australia is shown to use the introduced European snails Cernuella virgata and Cochlicella barbara as first intermediate hosts, and the same two species and Theba pisana as second intermediate hosts. The life cycle is typical of Brachylaima species. The parasite is capable of infecting at least two species of native Australian rodent, Rattus fuscipes and Leporillus conditor. Because of the intermediate hosts used, it is hypothesized that this trematode species has been introduced from Europe. The parasite may be conspecific with one of a number of described European species but difficulties with the literature concerning these species have required that the present form be designated only as Brachylaima sp. PMID- 2242963 TI - Routine screening for potential babesicides using cultures of Babesia bovis. AB - A procedure for screening of potential anti-malarial agents, based on the incorporation of [3H]hypoxanthine by the parasite, was adapted for the testing of anti-metabolites against Babesia bovis (Lismore and Samford isolates) cultured in vitro. A close correlation was found between [3H]hypoxanthine incorporation in a standard assay and percentage of parasitized cells as determined by microscopic examination. The concentrations of compounds causing 50% inhibition of [3H]hypoxanthine incorporation (ID50 values) for the established babesicides, Imidocarb and Amicarbalide, were determined to be 3 ng ml-1 (8.6 nM) and 5-10 ng ml-1 (17-34 nM), respectively. A variety of other anti-metabolites were tested in the system. ID50 values for some of the more effective compounds were tubercidin (75 nM), tetracycline (25 microM), menoctone (100 nM) and TN 108, a di-Mannich base derived from 4-(7'-trifluoromethyl-quinolin-4'-ylamino)phenol (0.13 microM). No significant differences between results with the two isolates of B. bovis were observed. PMID- 2242964 TI - Correlation between beta 2-microglobulin and soluble interleukin-2 receptor levels in plasma of individuals living in a malarial endemic region. AB - beta 2-Microglobulin (beta 2m) levels were related to the expected immunoprotection in 81 individuals living in a malarial mesoendemic area near Bobo-Dioulasso (Burkina Faso), who were longitudinally followed. Soluble interleukin-2 receptor (sIL-2R) levels were positively correlated to those of beta 2m (r = 0.44; n = 237; P less than 0.001). This suggests that most of the beta 2m could have originated from activated T and B cell membrane turnover. In our study, both beta 2m and sIL-2R were inversely related to IgG antibodies (Ab) against somatic antigen of Plasmodium falciparum (Som-Ag). Therefore, these molecules at high levels could have a down regulating activity, directly or indirectly, on B cells producing this kind of Ab. PMID- 2242965 TI - Protagonism of the arterial circulation in the preservation of the pig's liver by simple perfusion and hypothermic storage. AB - A modified technique to perform the successive perfusions of the liver that are necessary for its preservation by the simple perfusion method and hypothermic storage is presented. This technical variety has been tested on Large White pig's livers and consists in doing the successive perfusions of cooling, preservation and washout, first through the hepatic artery and there after through the portal vein. The macroscopic and biochemical characteristics of the effluents obtained through the infrahepatic inferior vena cava during the perfusion-washout of the livers at the end of the period cold ischemia shows its effectiveness. Likewise, the hepatic perfusion-washout begun via the arterial vein and finished via the portal one avoids post-revascularization hyperpotassemia in the receptor animals. It is hypothesized that the arterial protoganism of perfusions, when the simple perfusion and hypothermic storage method of hepatic preservation is used, could be a prophylaxis against complications of a post-transplant biliary origin. PMID- 2242966 TI - Delaying rejection in discordant heart xenografts in the rat: efficacy of cyclosporin, prostaglandin I2 and exchange transfusion. AB - If effective modes of prevention of hyperacute rejection were available, the problem of the absence of enough suitable donors could be solved by the use of organ xenografts. Organ xenograft rejection is principally mediated by preformed antibodies which are responsible for the hyperacute pattern of rejection. We decided therefore to study various methods of prevention of rejection in the guinea pig to Lewis rat combination (donor-recipient discordant species) in which hyperacute rejection is particularly intense. Three series of experiments were performed. In the first series immunosuppression of the recipient was induced using an oral solution of cyclosporin A. In the second series antiplatelet aggregation therapy was administered to the recipient, using intravenous prostacyclin (PGI2). In the third series antibody depletion of the recipient was attempted using exchange transfusion with or without prostacyclin perfusion. The most significant (p less than 0.01) prolongation of graft survival time was observed when combining exchange transfusion (8 ml) and PGI2 infusion (620 ng/kg/min). This observation suggests that, if antibody depletion in the recipient is the primary goal, measures aiming at reducing the consequences of the antigen-antibody reaction are also necessary to improve the results of organ xenografting. PMID- 2242967 TI - Diagnosis, management and complications of oesophageal and airway foreign bodies. AB - A five-year experience at the University of Ilorin Teaching Hospital with 52 patients with oesophageal foreign bodies, six patients with airway foreign bodies and two patients with both oesophageal and airway obstruction from foreign bodies is presented. Our use of jet anaesthetic ventilation for endoscopic removal of airway foreign bodies, clinical features and management problems of foreign body patients are also presented. Oesophageal diameters at six levels including those known conventionally as constrictions and dilatations were measured at autopsy in 40 foetuses and neonates constituting a randomized quarter of a larger series. Oesophageal diameters were found to be wider just below the cricopharyngeus muscle than at the bronchoaortic constriction or midway between this constriction and the cricopharyngeus. The conclusion is drawn that the frequent impaction of foreign bodies at the so-called superior oesophageal constriction has little or no anatomical basis referrable to oesophageal diameters as measured in the cadaver. PMID- 2242968 TI - Reasons behind surgical failures in thoracic outlet syndrome. AB - Possible reasons for surgical failures in TOS were investigated. The importance of accurate clinical diagnosis is pointed out and differential diagnostic problems are reported. Transaxillary first-rib resection is recommended, supplemented by further intervention, if necessary. The term "surgical failure" is explained, ways of avoiding intraoperative complications detailed and the importance of complex post-operative treatment emphasized. PMID- 2242969 TI - Immediate transposition of a latissimus dorsi muscle for correcting a postquadrantectomy breast deformity in Japanese patients. AB - With the aim of improving cosmetics after quadrantectomy, an immediate transposition of latissimus dorsi muscle was carried out. Cosmetic breast changes in transposed and non-transposed patients were evaluated by a Moire topography camera. To date, the breast deformity in five patients has been corrected only by conization of the residual breast tissue, and the breast deformity in the other five patients has been corrected by transposed latissimus dorsi muscle. Postoperative appearance and topography showed satisfactory symmetry of breasts in the transposed patients, when compared with the non-transposed patients. We conclude that the immediate transposition of latissimus dorsi muscle is useful for preventing post-quadrantectomy breast deformity. PMID- 2242970 TI - Treatment of parotid gland tumors. AB - A clinical review has been made of 55 patients who underwent surgery for parotid tumors between 1972 and 1987. The incidence of pleomorphic adenomas was 61.8%. The F.N.A.B. permitted us to reach a correct preoperative diagnosis in 94% of the cases. The surgical procedures we used were: enucleation in eight cases, enucleoresection in five cases, superficial parotidectomy in seven cases, total conservative parotidectomy in 28 cases, total parotidectomy sacrificing the facial nerve in four cases, extended surgery in three cases. For these last three patients a cycle of postoperative radiotherapy for a total of 6000-6500 R. was carried out. As regards complications and sequelae, we must report: temporary lesions of the facial nerve (12.76%), permanent lesions (17%), Frey's syndrome in 10.61%, while a salivary fistula arose in 6.38% of the cases. The follow-up of 47 patients allowed us to observe three recurrences in cases of pleomorphic adenomas (two after enucleoresection and one after superficial parotidectomy), three recurrences in malignant tumors treated with surgery and one recurrence after combined treatment surgery and radiotherapy. PMID- 2242971 TI - The role of selective beta 1-blocker in the preoperative preparation of thyrotoxicosis: a comparative study with propranolol. AB - Subtotal thyroidectomy was performed for hyperthyroidism on 130 patients; 95 treated before surgery with propranolol (Group I) and 35 given only metoprolol before surgery (Group II). These patient groups were compared with reference to preoperative medication, operative and immediate postoperative course, and late results with follow-up for one to five years. Clinical response was 100% in group II and 94.7% in group I. The median length of preoperative treatment was 7.96 +/- 1.84 days in group I and 6.25 +/- 1.73 days in group II (P less than 0.05). There were no serious adverse effects of the drugs in either treatment group. No anaesthesiologic or cardiovascular complication occurred during operation in either group. Ten patients in group I (10.5%) and six patients in group II (11.4%) observed hyperthyroid manifestations in the immediate postoperative period, eliminated by the administration of the propranolol/metoprolol, and no case of thyroid storm occurred. One patient in group II developed clinical hypocalcaemia. Two patients, one in each group, presented temporary unilateral recurrent laryngeal nerve paralysis. There were two recurrences of toxicity in group I (2.1%) and none in group II. Hypothyroidism occurred in 3 patients (2.3%) two of them were from group I and one was from group II. The postoperative hospital stay was 4.62 +/- 1.61 days in group I and 2.81 +/- 1.32 days in group II (P less than 0.05). One patient from group I died on the third postoperative day due to pulmonary oedema. The results suggest that metoprolol can be safely used and offers the advantages of desired clinical response, shorter preoperative preparation time, simplicity of dosage and shorter postoperative hospital stay in comparison to propranolol for preoperative treatment of hyperthyroidism. PMID- 2242973 TI - Use of adhesive tape for primary closure of surgical skin wounds. AB - Although, during the last half century, there has been plenty of evidence that the healing of skin wounds is hindered by suture closure and fostered by the use of surgical tapes, the latter technique has not been widely practiced, because the adhesiveness of surgical tapes has been deemed too unreliable. When used at all, tapes have generally been applied only over subcuticular and subcutaneous sutures. The author describes his experience in using a new transparent adhesive tape for primary wound closure of 37 surgical incisions without underlying sutures. The series involved a wide range of surgical wounds, in various portions of the body. In all cases, the results were excellent; neither major nor minor complications were observed. Compared with suture closure, this method was associated with a reduced potential for infection, faster renewal of tensile strength, greater cost effectiveness, and better cosmetic effects. PMID- 2242972 TI - Preventing postoperative deep venous thrombosis in gynecological surgery with defibrotide. AB - This was an open, fully randomized clinical study designed to compare the effectiveness and tolerability of defibrotide and calcium heparin as prophylactic agents for preventing postoperative DVT of the lower limbs in patients scheduled for gynecological surgery for nonmalignant disease (100 cases) or for tumoral pathology (60 cases). Defibrotide was administered by intramuscular injection in doses of 400 mg b.i.d., starting one day before surgery and continuing for seven postoperative days (n = 80); calcium heparin was given by subcutaneous injection in doses of 5000 IU t.i.d., starting two hours before surgery and continuing likewise for seven days (n = 80). DVT was to be diagnosed by computerized impedance plethysmography. Not a single case of DVT occurred in either treatment group; nor were there any significant differences in the magnitude of surgical or postoperative bleeding or in pertinent laboratory test returns. The Authors conclude that defibrotide can be used to advantage instead of calcium heparin as a measure for preventing DVT of the lower limbs in patients undergoing major surgery for gynecologic disorders including malignancy. PMID- 2242975 TI - Frozen section diagnosis: a quality control study. AB - In a quality control study we reviewed six hundred and eighty one frozen section specimens sent to our department from 1981 to 1989. Accuracy was 98%. Diagnosis was deferred in 1%. False positive diagnosis for malignancy was made in one (0.15%) case and false negative diagnosis for malignancy in thirteen (2%) cases. Most of the inaccurate diagnoses concerned the female breast and the omentum. Incorrect diagnoses were due to interpretation of the pathologic findings (50%), to microscopic sampling (36%) and to gross sampling (14%). Some of the lesions are difficult to diagnose even in permanent sections. Technical skill and diagnostic expertise are essential for high diagnostic accuracy in the method of frozen section. PMID- 2242974 TI - Emergency large-bowel surgery in a tropical environment: approach and outcome. AB - In 87 of 90 consecutive patients aged between 24 hours and 72 years operated upon for large bowel emergencies, 79.3% were for acute obstruction and 20.7% for perforation. Following a management policy of safety first, 46 (52.9%) patients had primary colonic resection with 25 (54.3%) of these primarily anastomosed (treatment group I), and 21 (45.7%) exteriorized (treatment group II). Twenty one (24.1%) patients with simple obstruction had reduction (treatment group III) and 27 others (31.0%) had colostomy alone after laparotomy (treatment group IV). In treatment group I, the mean hospital stay was 21 days, and the clinical leak rate was 8%. The mean hospital stay for treatment groups II-IV were, respectively, 36, 13, 69 days. There were nine (10%) deaths in hospital, six (6.9%) of these postoperatively, 11 (12.6%) septic complications and three (3.4%) wound failures in the series. The hazards of large bowel surgical emergencies can usually be minimised by primary resection, anastomotic integrity, avoidance of primary anastomosis or closure of laceration when hazardous and a judicious use of systemic and topical antibiotics in a well resuscitated patient. PMID- 2242976 TI - Parotid gland metastasis from renal carcinoma. AB - The salivary gland most frequently involved with secondary cancer is the parotid gland. Metastases are responsible for 21-42% of malignant parotid tumors. Malignant melanoma and squamous cell cancer are the two most common tumors to metastasize to the parotid gland. Metastatic adenocarcinoma to this site has rarely been reported. Secondary renal cell carcinoma has been reported in many structures, including the brain, sinonasal tract, lungs, abdomen, genitourinary tract, bone, soft tissue, and lymphatics. Histologically proven parotid metastasis has been previously reported in only one patient. Two patients have recently been diagnosed and treated at our institution for this rare disease. The clinical presentation of each patient was quite different. One patient presented with parotid and pulmonary metastases seven years after resection of a renal tumor. Another patient had resection of a parotid mass revealing an occult metastasis from a renal cell carcinoma. Further evaluation revealed a locally extensive asymptomatic hypernephroma. The survival from the time of discovery of the parotid metastasis was 46 months for the former patient, while the latter patient is alive after 20 months. Differentiation of these tumors from vascular disorders (aneurysm or arteriovenous fistula) required selective angiography and computed tomography. Surgical excision via superficial parotidectomy with facial nerve preservation is necessary for palliation, particularly to avoid massive hemorrhage which may occur upon tumor extension into the oropharynx. PMID- 2242977 TI - [Continuing education. Tachycardic arrhythmias]. PMID- 2242978 TI - [HIV infections]. PMID- 2242979 TI - [HIV-associated opportunistic diseases: diagnostic and therapeutic possibilities in the clinic and general practice]. PMID- 2242981 TI - [Integrated management of the HIV positive patient--medical, psychological and psychosocial aspects]. PMID- 2242980 TI - [HIV infection of the central nervous system: clinical relevance]. PMID- 2242982 TI - [Possibilities and limits of the epidemic regulation in relation to the control of AIDS]. PMID- 2242983 TI - [New aspects in HIV diagnosis]. PMID- 2242984 TI - [Therapy and immunologic prevention of HIV infection]. PMID- 2242985 TI - [Septic temperatures and throat pain in a patient with hyperthyroidism]. PMID- 2242986 TI - [33-year-old patient with recurrent bouts of fever and splenomegaly after foreign travel. A contribution to diagnosis and therapy of brucellosis]. PMID- 2242987 TI - [A 65-year old jaundiced patient with weight loss, fever and sicca syndrome]. PMID- 2242988 TI - [Endemic sprue--a case of "baker's intestine"?]. PMID- 2242989 TI - [Comment on the contribution by R. Ziesche and H. Matthys: "Diagnosis of pleural effusions" in Internist, volume 31, April 1990, p. 272-6]. PMID- 2242990 TI - Selective binding of a 30-kilodalton protein to disposable hydrophilic contact lenses. AB - To investigate the accumulation of tear proteins on disposable extended-wear contact lenses (42% Etafilcon A and 58% hydration), a technique involving sodium dodecyl sulfate-polyacrylamide minigel electrophoresis combined with a sensitive silver-staining method was used. Besides the binding of large amounts of tear lysozyme the authors found an accumulation of an as yet unidentified 30 kilodalton (kD) protein. Longitudinal experiments showed lysozyme binding after 1 day of lens wear. The 30-kD protein was detected after a 2-day wearing period. The fact that protein deposition occurs during the relatively short wearing period of these lenses (1 week) may explain the unexpectedly high incidence of contact lens-associated conjunctivitis observed with these lenses. PMID- 2242991 TI - The role of class II antigen-expressing cells in corneal allograft immunity. AB - The goal of this study was to investigate the relationship between the presence of Class II antigen-expressing cells (Class II+) cells in the cornea and the generation of allograft immunity. Wistar/Furth (W/F) rat Class II+ cells were injected in various numbers (0.01, 0.1, 1.0, 5.0, 10.0, and 20.0 X 10(6) into the corneal stroma of Fischer 344 (F344) rats. For comparison, the same numbers of W/F Class II+ cells were injected directly into the peritoneal cavity of F344 rats. Also, W/F cells were injected into the corneas of F344 rats and the corneas were "grafted" intraperitoneally in F344 hosts. The results showed that up to 20 X 10(6) class II+ cells injected in situ into the corneal stroma did not elicit a serum cytotoxic antibody response or a splenic or blood cytotoxic T-cell response against donor Class II antigens. In contrast, systemic immune responses were elicited by both direct intraperitoneal injection of large numbers (10 or 20 X 10(6] of allogeneic Class II+ cells and by intraperitoneal grafting of syngeneic corneas carrying similar numbers of allogeneic Class II+ cells. F344 recipients of a syngeneic cornea containing 10 or 20 x 10(6) W/F Class II+ cells or a suspension of W/F cells exhibited an accelerated rejection of W/F skin allografts (13.3 versus 9.0 days, first- versus second-set rejection). These results indicate that the number of Class II+ cells required to elicit a systemic immune response is larger than the number of Class II+ cells present in the normal cornea. PMID- 2242992 TI - Low-dose ultraviolet-B irradiation of donor corneal endothelium and graft survival. AB - Donor rabbit corneal endothelium was pretreated with different doses of ultraviolet (UV-B) irradiation (302 nm) before grafting to test whether allograft survival could be favorably affected in comparison with untreated corneas grafted into the same recipients. Endothelial rejection was observed in 19 of 32 (59%) eyes that received no treatment compared with five of 32 (16%) eyes that received UV-B (P less than 0.001), and increasing doses of UV-B were associated with lower rejection rates (P less than 0.05). Although exposure of donor endothelium significantly reduced endothelial rejection at all doses tested, it resulted in primary graft failure in a substantial proportion of corneas treated at high doses. Class II (Ia) antigen staining of corneal tissue was present in conjunction with clinical evidence of rejection, and the magnitude of staining correlated with the histologic extent of inflammation. Scanning electron microscopy revealed various endothelial cell surface irregularities and membrane defects in high-dose UV-treated corneas. Endothelial cell cultures exposed in vitro to UV-B light showed a dose-dependent loss in cell viability. These data suggest that UV-B pretreatment of donor corneal endothelium prolongs graft survival but that toxic side effects must be carefully controlled. PMID- 2242993 TI - Movements of cultured corneal epithelial cells and stromal fibroblasts in electric fields. AB - The effects of an externally applied direct-current electric field on the movement of cultured rabbit corneal epithelial cells and stromal fibroblasts were studied. After a latency of approximately 20 minutes in an electric field, both epithelial cells and stromal fibroblasts became spindle shaped and underwent galvanotropism by aligning their long axes perpendicular to the applied electric field. The electric field stimulus thresholds for galvanotropic movements in epithelial cells and stromal fibroblasts were 4V/cm and 6 V/cm, respectively. After an additional latency of 30 minutes, both cell types manifested galvanotaxic movements: epithelial cells commenced migration in the cathodal (downfield) direction and stromal fibroblasts in the anodal (upfield) direction. For both types of cells, ruffled membranes and lamellipodia were abundant at the leading edges of migrating cells and cell processes underwent retraction at the trailing edges. At field strengths of above 10 V/cm, evidence of cellular damage (manifested by cellular rounding and detachment), attributable to the electric field treatment, was observed after 4 hours. These preliminary results suggest that galvanotaxic responses could be exploited clinically in the enhancement of corneal wound healing. PMID- 2242994 TI - Rod visual fields in cone-rod degeneration. Comparisons to retinitis pigmentosa. AB - Dark-adapted visual fields to short- and long-wavelength stimuli were obtained from 20 patients with cone-rod degeneration, 20 patients with retinitis pigmentosa, and ten normal subjects. Patients were selected because they retained rod electroretinographic (ERG) function over a sufficient range for the Naka Rushton analysis of retinal illuminance versus amplitude functions. Patients with cone-rod degeneration retained a relatively normal field topography although overall sensitivity was reduced. The mean sensitivity loss was consistent with a small elevation in ERG semisaturation constant and minimally delayed rod b-wave implicit times. Rod visual fields from patients with retinitis pigmentosa retaining rod ERG function were consistent with log sensitivity profiles reported previously for type 2 patients. Sensitivity loss was greatest in midperipheral regions, with most patients showing least loss in the far periphery. Disproportionate loss in the midperiphery is consistent with a large elevation in the ERG semisaturation constant and prolonged rod b-wave implicit times. PMID- 2242995 TI - Quantitative analysis of retinal hemodynamics using targeted dye delivery. AB - A new method designed to allow repeated mapping of retinal hemodynamics on a macro- and microcirculatory level was evaluated in the primate eye. The method, called "targeted dye delivery," consists of encapsulating a fluorescent dye in temperature-sensitive liposomes, injecting the liposomes systemically, and using a light pulse from an argon laser to release a bolus of dye in a targeted retinal vessel. The follow-up of the well-defined dye front thus generated allows calculation of the blood flow and capillary transit time. Evaluation of targeted dye delivery in a monkey indicated that centerline blood velocity and the vessel diameter can be measured with a reproducibility of 10% and 4%, respectively, in vessels that are 40 microns and larger. These measurements yielded flow values that had a reproducibility of 10% on the same day and 13% on different days. The normalization of flow rate by the vessel diameter was consistent with theoretic estimates and promises to be a circulation indicator independent of variations between individual and species. The transit time across capillary beds at different locations was found to be similar, thus indicating that the method could be used to evaluate the local viability of the microcirculation. PMID- 2242996 TI - Thrombin contracts isolated bovine retinal small arteries in vitro. AB - The effect of thrombin was tested in vitro on rings of bovine retinal small arteries (internal diameter approximately 200 microns). Cumulative addition of thrombin (0.001-10 units/ml) induced a variable concentration-dependent contraction of the retinal arteries. The contractions were slow in onset and reached a plateau after 5-8 minutes when thrombin was added cumulatively to the organ bath. Two vessels remained contracted greater than 1 hour after wash-out of thrombin. Maximum vessel contraction induced by thrombin was equal to 43% of the vessel Emax (1.36 N/m), with an effective concentration at the 50% level of 0.04 units/ml. Vessel contraction induced by 1 unit/ml of thrombin was, in contrast, transient, reaching a maximum within 2-4 minutes. Thereafter the vessel tension declined again almost back to baseline within the next 10-20 minutes. Contractions to thrombin could not be repeated nor could it be elicited with thrombin inactivated with heat or antithrombin-III. Treatment of vessels with 10( 6) M phenoxybenzamine had no effect on the thrombin-induced vessel response. These findings indicate that the contractile effect of thrombin depends on its catalytic activity. Indomethacin at a concentration of 10(-5) M did not affect the thrombin-induced vessel response. Methylene blue at a concentration of 3 X 10(-6) M potentiated the thrombin-induced response in the larger, greater than 200-microns diameter retinal arteries. The ensuing relaxation of the arteries, after maximal tone was reached, was slower than in the control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2242997 TI - Shedding of rod outer segments is light-driven in goldfish. AB - Rod outer segment (ROS) shedding in goldfish was quantified by measuring the number of phagosomes in the retinas of goldfish that were maintained under natural or artificial cyclic light, constant light, or constant dark conditions. Fish maintained in cyclic light, whether natural or artificial, had robust daily rhythms of ROS shedding. The ROS tips were shed primarily during the light phase of the cycle, and maximum shedding occurred 2-4 hours into the light period. Fish maintained for 1, 3, or 7 days in constant light or constant dark had no daily rhythms in ROS shedding. In these fish, ROSs lengthened, on average, 2.3 microns/day in constant light and 1.5 microns/day in constant dark. After 3 days in constant light, shedding was induced by placing fish in darkness for 2 hours, then returning them to light. Placing fish in darkness for 0.5 hours did not induce shedding, nor did placing them in darkness for 3 hours without returning them to light. ROS shedding thus appears to be goldfish is completely dependent on changes in ambient illumination; no circadian or endogenous components were found. Previous observations of circadian changes in behavioral visual sensitivity therefore cannot be due to endogenous changes in ROS length. PMID- 2242998 TI - Rod outer segment length and visual sensitivity. AB - Detection threshold for the rod system was measured psychophysically in adult goldfish before and after exposure to constant illumination of 340 lux (91 microW/cm2) for 7 days. As shown in the previous paper, rod outer segment (ROS) length increases an average of 60% under these conditions. The present work shows that visual sensitivity also increases, in approximate proportion to the additional optical density predicted by the longer ROSs. These results are the first to show that exposure to constant light can enhance visual sensitivity. They imply further that detection threshold is related to ROS length. Apparently, the photopigment in the ROS tips that is normally shed on a daily basis retains its photon-catching ability. PMID- 2242999 TI - The safety of intravitreal hyaluronidase. A clinical and histologic study. AB - The authors previously developed a new model of preretinal neovascularization in the rabbit eye using hyaluronidase for enzymatic vitreolysis. The purpose of this study was to evaluate the safety of intravitreal injections of hyaluronidase. Concentrations of 1, 15, 30, 50, and 150 IU of hyaluronidase in 0.1 ml of 0.9% saline were injected intravitreally and aspirated repetitively until the vitreous was partially liquified. The animals were examined with indirect ophthalmoscopy, fundus photography, and fluorescein angiography before injection and on days 1 and 7 after injection. Light and electron microscopic retinal sections were prepared from enucleated eyes at days 1 and 7. All concentrations of hyaluronidase were effective in producing partial vitreolysis. Eyes treated with 1 IU showed no abnormalities on days 1 or 7. Eyes treated with 15 IU showed no retinal abnormalities on day 1, but on day 7 histologic abnormalities were present in two of four eyes. At higher concentrations, clinical and histologic changes were seen in proportion to the concentration and included focal whitening, edema, vitreous haze, vascular abnormalities, and retinal necrosis at the highest doses. Histologic evaluation of the retina revealed marked destruction in all layers at the higher concentrations. The authors conclude that 1 IU of intravitreal hyaluronidase is sufficient for partial vitreolysis and nontoxic to the rabbit retina. PMID- 2243000 TI - A longitudinal study of the relationship between intraocular and blood pressures. AB - The relationship between intraocular and systemic blood pressures was investigated in a prospective study of 572 middle-aged men. There was no consistent relationship between intraocular pressure at first visit and age. Subjects with an intraocular pressure greater than 20 mm Hg had a significantly higher systolic blood pressure than controls matched for age. An autoregressive model was used to examine the relationship between change in intraocular pressure and initial intraocular pressure, age, and blood pressure. When the authors compared data obtained 1 or 2 years apart, a change in intraocular pressure was positively correlated with a change in systolic blood pressure. Thus, the results of this study indicate that changes in intraocular pressure over time are associated with changes in systolic blood pressure and that intraocular pressure does not necessarily increase with age. PMID- 2243001 TI - The influence of intraocular pressure on visual field damage in patients with normal-tension and high-tension glaucoma. AB - There have been several reports to suggest that the type of visual field damage in open-angle glaucoma is influenced by intraocular pressure (IOP). This study was undertaken to determine the extent to which patients with normal-tension (NTG) and high-tension glaucoma (HTG) could be differentiated on the basis of some features of their visual fields. The results from 40 pairs of NTG and HTG patients were matched closely for the extent of visual field damage, pupil size, and visual acuity. Using this pooled material, the authors increased the IOP difference between the two groups in either direction, ie, by either progressively lowering the highest recorded IOP allowed for inclusion in the NTG group or by progressively increasing that required for inclusion in the HTG group. They compared the normal areas of the patients' visual fields by using simple visual field indices designed to quantify the undisturbed field. Using receiver operating characteristics (ROC) analysis, they showed that changing the inclusion criterion in the NTG group resulted in no better separation between the groups. However, when the inclusion criterion was changed in the HTG group, the two groups tended to become more separable. In this case, the degree of separation appeared to be related to the difference in the highest recorded IOP between the two groups although the separation was not complete. These findings show that pressure has a greater influence on the type of visual field damage at the higher end of the IOP spectrum encountered in open-angle glaucoma and suggest that there is no common single pathophysiologic mechanism in this disease. PMID- 2243002 TI - A study of variance in densitometry of retinal nerve fiber layer photographs in normals and glaucoma suspects. AB - The main object of this research was to develop a reliable method of screening glaucoma suspects and patients for early loss of or changes in the retinal nerve fiber layer (RNFL). This study quantifies the variances due to photography, digitizing, and analysis of red-free photographs of the RNFL. The influence of pupil size, optic disc position and eye movements, film processing, digitizing, and intra- and interphotographic-session and intra- and interoperator variances were established. It was found that pupils needed to be dilated to at least 6 mm, that the optic disc had to be positioned in a standardized area in the negative, that the head of the subject had to remain still during photography, and that film processing and digitizing of the negative needed to be strictly controlled to minimize the variance in collection of densitometry data from RNFL red-free photographs. It was established that focusing of the negatives during digitization was not crucial. Criteria were defined for acceptable negatives. Interphotographic-session and intraoperator variances were not significant in most cases when negatives were digitized to these criteria. Analysis of interphotographic-session variance showed that there were still some factors in photography, film processing, and/or image digitizing that were not sufficiently controlled for long-term follow-up without normalization of the data. Densitometry data gathered using the established protocol, from negatives of 71 subjects were analyzed; best sensitivity and specificity rates of 80% and 100%, respectively, were achieved for the diagnosis of glaucoma. PMID- 2243003 TI - Absence of time-dependent facility increase ("washout") in the perfused enucleated human eye. AB - During the course of constant-pressure anterior chamber perfusion experiments in eyes from a number of species, measured outflow facility increases progressively with perfusion time. One possible explanation for this phenomenon has been that the technique of perfusion induces a loss of extracellular material from the outflow pathway. Therefore, this general observation has been termed the "wash out" effect. Data from the authors' laboratories demonstrate that although outflow facility increases in cynomolgus monkey eyes by 26% and 42% from baseline over 90 minutes in vivo and in vitro, respectively, this does not occur in the enucleated human eye. The absence of washout in the human eye probably cannot be explained by postmortem conditions since enucleated monkey eyes undergo a similar magnitude of washout as the monkey eye in vivo. Furthermore, since washout does not occur in the perfused human infant eye, the age of the donor cannot explain the difference in washout properties between human and other primate eyes. The monkey eye in vivo is a valuable model in the study of outflow physiology. However, the difference in washout behavior between human and other primate eyes may point to a potentially important fundamental difference in the biology of the outflow pathways in these two species. PMID- 2243004 TI - Factors affecting therapeutic concentration of topical aminocaproic acid in traumatic hyphema. AB - Epsilon-aminocaproic acid (EACA) decreases rebleeding in traumatic hyphema through antifibrinolytic activity. Therapeutic levels were achieved in aqueous humor of rabbits after topical application. Aqueous humor EACA levels were significantly higher after pretreatment with 0.5% proparacaine. Use of EACA (60%) in a carboxypolymethylene (CPM) vehicle (0.5%, 1%, 2%, 3%, and 4%) was examined. Aqueous humors levels at 4 hours ranged from 6.18-20.42 micrograms/ml. The 2% and 3% formulas achieved the highest concentrations in aqueous. Use of EACA (15%, 30%, 40%, and 60%) in 4% CPM was also studied. At 2 and 4 hours after treatment, the 30% EACA solution most effectively achieved therapeutic levels. Velcro closure devices were attached to the rabbit's eyelids, and 200 microliters of 30% EACA in 2% CPM was administered. After 3 hours the patched eyes had a mean aqueous EACA level of 60.09 micrograms/ml compared with 8.97 micrograms/ml in unpatched eyes. When dose size was studied in patched eyes, 200-microliters doses achieved aqueous levels of 60.09 micrograms/ml, and 100-microliters doses resulted in levels of 10.40 micrograms/ml. Since epithelial toxicity was observed in eyes that had been patched, the optimum topical regimen appeared to be 200 microliters of 30% EACA in 2% CPM every 6 hours in unpatched eyes. PMID- 2243005 TI - Enhancement of differentiation of human lens epithelium in tissue culture by changes in cell-substrate adhesion. AB - Differentiation of human lens epithelial (HLE) cells cultured in vitro was drastically accelerated when the cells were cultured on cell-substrate adhesion free surfaces. Spontaneous differentiation of the lens epithelial cells in monolayer cultures could be recognized with the appearance of lentoid bodies after 40-50 days if maintained without further passage. Although dissociated HLE cells reconstituted into monolayers consistently on the haptotactic substrates (either gold-coated biopore membrane or regular plastic dishes), the cells from the same batches exclusively formed cell aggregates when cultured on either biopore membrane or agarose-coated plastic dishes (nonhaptotactic). The cells on nonadhesion substrate first aggregate, then synchronously develop into lentoids by the 10th day of culture. The differentiation of HLE cells into lentoid structures with lens-fiber characteristics was documented by both ultrastructural and biochemical markers, such as loss of cytoplasmic organelles, formation of gap junctions, and the expression of gamma-crystallin and MP26. The system, in which differentiation of epithelial cells can be induced predictably in a short period of time, provides an excellent model for the study of differentiation and gene expression in human lens cells cultured in vitro. PMID- 2243007 TI - Prevalence of anisometropia in volunteer laboratory and school screening populations. AB - For 10 years our laboratory has conducted, a longitudinal study of focusing and motor behavior of a volunteer population of 686 subjects aged 3 months to 9 years. Its purpose is to characterize normal refractive development in infants and children and to relate refractive anomalies to subsequent visual problems. Using age-related criteria for anisometropia adjusted to detect the most unusual 5% of the refractions on a test battery, we have found 19 nonstrabismic, anisometropic subjects (2.8% of total subject population). Of these, eight were either seen once or their anisometropia appeared at their last visit. Of the remaining 11 subjects, all had a reduction of their anisometropia to within normal limits on subsequent visits. Thus our current best estimate of persistent infant anisometropia is 0%, a startling result. By comparison, we found ten strabismic subjects (1.46%), two of whom had persistent anisometropia. Although we did not believe that anisometropic subjects could self-select and not participate in the study, it was possible that the volunteer laboratory population had characteristics atypical of the county at large. Thus we conducted a screening of 374 Head Start and first-grade pupils throughout the county, using the same methods. We found virtually no difference in the average refractive conditions between the laboratory and school populations and no significant difference in the prevalence of visual disorders. The very low prevalence of anisometropia in infants and young children in both populations has important implications for the etiology of anisometropic amblyopia. PMID- 2243006 TI - Ciliary muscle muscarinic binding sites, choline acetyltransferase, and acetylcholinesterase in aging rhesus monkeys. AB - Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity, and the affinity and number of muscarinic binding sites (as reflected by specific 3H quinuclidinyl benzilate binding) were determined in the ciliary muscle of rhesus monkeys ranging in age from 1-34 years. No age dependence was evident for any of these parameters. Within the limits of their specificity and precision, the data indicate that biochemical alterations in ciliary neuromuscular mechanisms do not account for the age-related loss of ciliary muscle configurational responses to topical pilocarpine and electrical stimulation of the Edinger-Westphal nucleus in the rhesus monkey. PMID- 2243008 TI - Diurnal variations in tonic accommodation. AB - It has been established that many aspects of visual function undergo diurnal changes, but accommodation is an apparent exception. The authors studied tonic accommodation in three subjects to challenge this assumption. The measurements were done in complete darkness with a modified Hartinger refractometer whose light source was replaced by a red photodiode. This allowed exposure of the refractometer mark for a short duration and thus eliminated the accommodation stimulus. The measurement were taken every 4 hours five times a day starting from 8 AM. Before each measurement the subjects were kept in darkness for 10 minutes. To obtain a measure of tonic accommodation the authors used the method of limits. The results showed that tonic accommodation varied over the studied period of the day in a predictable manner characteristics for each individual--one subject had his peaks and troughs displaced compared with the other two subjects. The amplitude of the daily variation was on the order of approximately 1.0 D, but the day-to-day values were relatively stable within +/- 0.5 D. Results were compared with other published data and showed that tonic accommodation may be subject to diurnal variation. PMID- 2243009 TI - Short-term fluctuation as an estimate of variability in visual field data. AB - The short-term fluctuation index (SF) is one of several values that provide an indication of a patient's response reliability during an automated perimetry examination. The authors investigated the number of visual field locations used and the number of determinations per location as factors affecting the SF estimate. A computer simulation program for perimetry was used to measure the SF index for 350 normal visual fields with various levels of response fluctuation. As expected, the variability of the SF estimate decreased as the number of locations used to estimate SF increased. There was a more important finding that, for an equal number of threshold estimates, a larger number of determinations at a smaller number of locations produced greater consistency in the SF estimate (eg, ten determinations at two locations instead of two determinations at ten locations). However, it is also important to sample from a representative spatial distribution of visual field locations. These results suggest that five determinations at four locations in the visual field is optimal for most clinical perimetric testing situations. PMID- 2243010 TI - Effects of prostaglandins F2 alpha, A2, and their esters in glaucomatous monkey eyes. AB - The effect of prostaglandin (PG) F2 alpha-isopropyl ester (IE), PGA2, or PGA2-IE on intraocular pressure (IOP) was tested in eight cynomolgus monkey eyes with argon laser-induced glaucoma. Dose-response testing and baseline IOP measurements were done. For multiple dose testing, 5 micrograms in 25 microliters (0.02%) of each PG was topically applied twice daily for 5 days. The IOP was measured at 30- or 60-minute intervals for 6 hours after the morning dose each day. A significant (P less than 0.05) reduction of IOP peaked at 5-9 mm Hg below baseline values on the 5th day of treatment for each PG. The ocular hypotensive effect of these PGs progressively became more pronounced during the course of twice-daily dosing, with a significant reduction maintained at least 17 hours after some doses. No more than trace aqueous flare and no cells were observed in any eye during the course of treatment. These findings demonstrate that PGs other than F2 alpha are potent ocular hypotensive agents in primates. PMID- 2243011 TI - Angiotensin-II contracts isolated human posterior ciliary arteries. AB - The effect of angiotensin-II (A-II) was studied on ring segments of the terminal extraocular branches of the posterior ciliary artery isolated from human enucleated eyes. It induced a potent concentration-dependent contraction on top of the spontaneous myogenic tone of all arteries studied from five patients with the concentration required to give half-maximal response equal to 51 nM. The spontaneous tone and maximal increase in vessel wall tension induced by A-II was equal to 51% of Emax. The relative response and sensitivity to A-II was unchanged in three endothelial denuded vessels, but the spontaneous tone increased. The arteries became completely insensitive to A-II after one exposure. These results show an immediate direct contractile effect of A-II on human posterior ciliary arteries, but the development of pronounced tachyphylaxis indicates that A-II is probably not an important factor in reducing blood flow to the optic nerve head. PMID- 2243012 TI - Decreased dopamine in the retinas of patients with Parkinson's disease. AB - Dopamine and it metabolites dihydroxyphenylacetic acid and homovanillic acid were measured in the retinas of eight patients with Parkinson's disease who died. They were divided into two groups according to their last dose of levodopa therapy. One group of three patients had not received levodopa therapy for at least 5 days before death, and the other group of five patients had received therapy 2-15 hours before death. Each patient was matched with controls for delay between death and freezing. In the three patients without levodopa therapy, the retinal dopamine content was lower than normal. In the five patients who received levodopa therapy before death, the retinal dopamine content was similar to that in the controls. This study is the first direct evidence to the authors' knowledge that retinal dopamine concentration is decreased in Parkinson's disease, as it is in the nigrostriatal pathway. PMID- 2243013 TI - Square arrays in early cortical lens opacities. AB - A combined freeze-fracture and scanning electron microscopic study of early opaque spots in the aging human lens showed the absence of gap junctions and the presence of square arrays in the membranes of disturbed fibers and neighboring unaffected fibers. Square arrays, with membrane particles of 6-7 nm, are considered as rearranged gap junctions and/or intramembranous particles, with particle sizes between 8.5-9.5 nm; they are a sign of electric and metabolic uncoupling. These ultrastructural observations lend support to the idea of an uncoupling mechanism in the aging human lens, conserving the transparency of unaffected parts of the lens, as postulated previously. PMID- 2243014 TI - The health policy and public health directorate of the Scottish Home and Health Department. PMID- 2243015 TI - Medicines regulation in the United Kingdom. AB - Modern society seeks pharmaceutical products which are safe, effective and of good quality. Many health workers may be unfamiliar with the licensing system for human medicines which attempts to ensure that those goals are attained. In the United Kingdom the legislative framework to attain these objectives is the Medicines Act 1968, together with relevant European Community Directives. This paper briefly describes an outline of the licensing structure, explains the steps by which a new human medicine may reach the market and gives an indication of current licensing procedures by describing some considerations in the handling of an application for a product licence. PMID- 2243016 TI - Delays in admission of patients with acute myocardial infarction to coronary care: implications for thrombolysis. AB - Of 408 patients presenting to a coronary care unit over a six month period 237 had an acute myocardial infarction. Two-thirds presented to hospital within three hours of the onset of symptoms. The median delay between arrival in hospital and admission to the Coronary Care Unit was 60 minutes. Only a minority of patients with acute myocardial infarction were eligible to receive thrombolysis, the most common exclusion criteria being an electrocardiograph that was not diagnostic of infarction at presentation. In-hospital transfer delay has increased considerably since 1972. It did not exclude many patients from receiving thrombolysis but it caused delayed thrombolysis. PMID- 2243017 TI - Introduction of an appointment system in a general practice: surveys of patients and staff. AB - To aid discussion on the introduction of an appointment system in an inner city practice with a 'walk-in' (non-appointment) system, we surveyed, firstly, patients' and staff members' attitudes to appointment systems, and secondly, aspects of the functioning of the current system. Of 250 patients in the first survey 73 per cent were against appointment systems while 24 per cent indicated that they would consider registering with another practice if such a system were introduced. Adverse comments about appointment systems greatly outweighed favourable ones. Staff members perceived clear advantages and disadvantages of both methods of consulting e.g. the 'walk-in' system was thought to be stressful due to the unpredictable workload but thought to reduce the demand for housecalls. Appointment systems were seen as giving staff more control over consulting but as less flexible for the patient. In the second survey of 352 patients, 17 per cent estimated a wait of 10 minutes or less for their consultation, 62 per cent estimated it as 10 to 20 minutes and 21 per cent as more than 30 minutes. Further, 68 per cent of patients estimated that their consultation lasted five minutes or less and 27 per cent indicated that the doctor seemed rushed. As a compromise between the wishes of patients and the needs of staff, 'walk-in' morning surgeries and appointment-only evening surgeries are now offered. PMID- 2243018 TI - Glasgow Council on Alcohol: trends and developments in a community based voluntary organisation (1968-1989). AB - Since 1968, Glasgow Council on Alcohol has steadily increased the scope and variety of its efforts to help problem drinkers and their families. Apart from a large increase in client numbers over the last 20 years, there has been a number of interesting developments in identifying 'at risk' groups and directing them into the helping process. Prevention of alcohol problems has also become a major issue for this agency. PMID- 2243019 TI - Evaluation of a Fife 'Novopen' clinic held within a diabetes patient education centre. AB - In common with other hospitals throughout the United Kingdom, a diabetic patient education centre has been established at the Victoria Hospital, Kirkcaldy. Many activities now take place within the centre including a 'Novopen' Clinic at which insulin requiring diabetic patients are converted to a multiple injection method of delivering soluble human insulin. An evaluation of the Novopen Clinic, including the first 60 patients attending, has demonstrated a statistically significant fall in random blood sugar estimations (mean fall 2.0 m.moles 1(-1), 95 per cent confidence intervals 1.5 m.moles 1(-1) to 2.5 m.moles) since conversion at the Novopen Clinic. Changes in mean daily insulin intake (mean increase of 1.6 units per day) and glycosylated haemoglobin (mean fall of 0.88 per cent) were not significant. One hundred per cent of patients surveyed described the Novopen Clinic as 'helpful' or very 'helpful'. Staff see the clinic offering significant opportunities for patient education. The estimated cost of the clinic per new patient was 147 pounds. PMID- 2243021 TI - Workshop for researchers in community care. PMID- 2243020 TI - The validation of a language and communication assessment procedure for use with adults with learning difficulties. AB - The aim of the research was to investigate the validity of a new procedure for assessing the communication skills of adult mentally handicapped people. At present there are no communication assessments designed for this client group. The procedure, known as the Communication Assessment Profile (CASP) was used with 202 adults selected from eight hospitals and 15 community placements. Results have shown that CASP is a reliable clinical tool, able to measure communication skills with accuracy, and sensitive to differences between adults living in hospital and community settings. This report provides a summary of the findings, the details of which are published elsewhere. PMID- 2243022 TI - General practitioner minor surgery. PMID- 2243024 TI - Preventing and detecting unique complications in the spinal cord injured. PMID- 2243023 TI - Behavioral management of urinary incontinence in homebound older adults. PMID- 2243025 TI - The Unna boot makes a comeback. PMID- 2243026 TI - Home care of the elderly alcoholic. PMID- 2243027 TI - Impaired skin integrity: a nursing diagnosis--a nursing challenge. PMID- 2243028 TI - Nursing management of the undeflatable Foley catheter balloon. PMID- 2243029 TI - Avoiding professional negligence: a review. PMID- 2243031 TI - The veterinarian as victim. PMID- 2243030 TI - The veterinarian's role in animal welfare. PMID- 2243032 TI - Hyperkalemic periodic paralysis in horses. AB - Eleven horses (3 mares, 7 stallions, 1 gelding) with clinical and biochemical evidence of hyperkalemic periodic paralysis were studied. Each horse had history of episodic weakness, muscular tremors, or collapse, which lasted for periods of a few minutes to hours. Diagnosis was based on hyperkalemia in association with a spontaneous episode of paralysis or by precipitation of an episode by oral administration of potassium chloride. Clinical and biochemical events were documented during spontaneous and induced episodes of muscular weakness. During episodes, electrocardiographic findings were consistent with hyperkalemia. Electromyography performed between episodes revealed fibrillation potentials and positive sharp waves, complex repetitive discharges, and myotonic discharges. Histologic changes in muscle biopsy specimens varied from no overt changes in some horses to vacuolation in type-2B fibers with mild degenerative changes in other horses. Electron microscopy of myofibers revealed dilatations of the sarcoplasmic reticulum. Analysis of blood samples taken serially during induced attacks in 5 horses revealed marked hyperkalemia (5.5 to 9.0 mEq/L), with normal acid-base status, hemoconcentration, and modest changes in muscle-derived enzymes. Close correlation (r2 = 0.882) between total plasma protein and plasma potassium concentrations was observed and indicated a shift of fluid out of the extracellular fluid compartment. Treatment of either spontaneous or induced episodes by IV administration of calcium, glucose, or bicarbonate resulted in rapid recovery. Dietary management or daily administration of acetazolamide effectively controlled episodes. An affected mare was bred to an affected stallion, and 3 affected offspring were produced by embryo transfer. Blood samples from another extended family of affected horses were analyzed for identification of a genetic marker.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243033 TI - Patterns of uterine prolapse in dairy cows and prognosis after treatment. AB - A 12-month study was undertaken in a 9-veterinarian dairy practice to determine patterns of uterine prolapse and factors associated with posttreatment survival. Of 220,000 cows in herds visited by veterinarians from the practice, 200 (0.09%) developed prolapses mostly (155/169 with data) in the first 24 hours after calving. Most cows (130/200) had prolapses during fall and winter months, and assistance was required in 47 of 200 calvings that resulted in prolapses. Treatment of affected cows (n = 196) consisted of cleansing and replacement of the uterus, insertion of perivulvar retention sutures, local and systemic administration of antibiotics, and parenteral administration of dexamethasone and oxytocin. Calcium was administered to cows with milk fever (n = 117) and to multiparous cows without milk fever attended by veterinarian 9 (n = 8). Crude recovery rate after 2 weeks was 72.4%, but recovery was significantly better if the calf was born alive (P = 0.001), the cow was primiparous (P = 0.03), the cow did not have stage-3 milk fever (P = 0.003), or if the cow was attended by veterinarian 9 (P = 0.01). Time to treatment was not significantly associated with recovery, but affected cows were treated mostly (127/156) within 2 hours of occurrence of the prolapse. By multivariable analysis, presence of a liveborn calf, parity, and lack of stage-3 milk fever, but not attending veterinarian, were significant (P less than 0.05) prognostic indicators of 2-week survival. PMID- 2243034 TI - Comparison of the effect of pneumonia detected during lifetime with pneumonia detected at slaughter on growth in swine. AB - Pneumonia in swine has been studied mainly at slaughter or necropsy. However, when performing slaughter or postmortem examinations, assessment of the true prevalence or lifetime extent of pneumonia is at best speculative. Radiography was used to evaluate lungs from pigs 21 to 150 days old. Follow-up slaughter examination was performed on pigs 180 days old. Individual percentage of pneumonia observed over the life of each pig and at slaughter were added to yield lifetime pneumonia scores. A significant (P = 0.0001) negative effect of lifetime pneumonia on growth rate was found. By comparison, slaughter examination proved to be a poor indicator of lifetime pneumonia; lesions were found to progress and regress dynamically throughout the life of pigs. PMID- 2243035 TI - Idiopathic granulomatous disease involving the skin in a horse. AB - Clinical signs of generalized granulomatous disease in a horse included depression, generalized lymphadenopathy, scaly skin, and dependent edema. Diagnosis was confirmed histopathologically by diffuse granulomas in more than one organ system (lymph nodes and skin), and by ruling out etiologic agents. Response to treatment with corticosteroids was favorable. The clinical features and response to treatment in this horse were different from classic textbook descriptions of equine generalized granulomatous disease. Equine granulomatous disease appears to be comparable to human sarcoidosis. To avoid confusion between human medical and veterinary medical terminology, the authors suggest that the equine disease be referred to as equine idiopathic granulomatous disease and that a complete diagnostic description should include a reference to the organ systems involved. PMID- 2243036 TI - Granulosa cell tumor in a mare with a functional contralateral ovary. AB - A functional corpus luteum was found in the ovary contralateral to the ovary with a granulosa cell tumor in a 24-year-old Standardbred mare. The mare was ovariectomized because she was to be used as a jump mare for collection of semen from stallions. The blood concentration of progesterone was 2.2 ng/ml, and the luteal tissue progesterone concentration was 6.3 micrograms/mg. Atrophy of the contralateral ovary is one of the major signs used in diagnosis of granulosa cell tumor; however, our findings indicate that the ovary contralateral to a granulosa cell tumor is not invariably nonfunctional. PMID- 2243037 TI - Congenital Neospora caninum infection in a calf with spinal cord anomaly. AB - Neospora caninum was identified in a calf with spinal cord anomaly in Australia. The calf was full-term and born dead. The caudal cervical and cranial thoracic segments of the spinal cord of the calf were asymmetric because of marked unilateral reduction of ventral gray matter and focal cavitation. Mild focal disseminated nonsuppurative encephalomyelitis was associated with N caninum tissue cysts. Tissue cysts were 16 to 35 microns X 10 to 27 microns, and the cyst walls were 1 to 3 microns thick. In an immunohistochemical test, the parasite stained with N caninum serum but not T gondii serum. PMID- 2243038 TI - Prednisolone and danazol for treatment of immune-mediated anemia, thrombocytopenia, and ineffective erythroid regeneration in a dog. AB - Immune-mediated anemia and thrombocytopenia were diagnosed in an 8-year-old spayed Miniature Schnauzer. The initial CBC indicated poor erythroid regeneration and concurrent leukopenia. The results of a Coombs test and ANA titer were strongly positive. Examination of a bone marrow specimen revealed erythrophagocytosis and a maturation arrest in the RBC series. Treatment with transfusion plus prednisolone and an attenuated androgen (danazol) resulted in stabilization of the PCV and the development of reticulocytosis. PMID- 2243039 TI - Double cervices in two llamas. AB - Double cervices were diagnosed in 2 female llamas that were infertile. The condition is uncommon in other species. The condition results from the failure of fusion of the mullerian ducts during embryonic development. Diagnosis was facilitated by vaginoscopy. One case was verified as didelphia, with 2 uterine bodies and 2 cervices. PMID- 2243040 TI - Prophylactic use of dantrolene associated with prolonged postanesthetic recumbency in a horse. AB - Dantrolene, a drug used in the prevention and treatment of malignant hyperthermia, was believed responsible for prolonged postanesthetic recumbency in a horse. Prophylactically, dantrolene was given orally before induction of anesthesia. Dantrolene has been recommended for use in horses at risk of developing postanesthetic myopathy. Side effects, including ataxia, may result from dantrolene administration. PMID- 2243042 TI - Accuracy of radiography of the reticulum for predicting surgical findings in adult dairy cattle with traumatic reticuloperitonitis: 123 cases (1981-1987). AB - Radiographic and surgical findings were compared in 123 cattle suspected of having traumatic reticuloperitonitis. Radiography of the reticulum proved to be a sensitive test for detection of a foreign body (FB). An abnormal FB position on a radiograph was a good predictor of FB perforation. If an FB was fully attached to a magnet, it was unlikely to be perforating the reticular wall. When abnormal reticulum size, abnormal reticulum location, and gas shadows adjacent to the reticulum were found simultaneously on a radiograph, hepatic or perireticular abscess was likely. Reticular radiography proved to be a useful diagnostic aid in cattle suspected of having traumatic reticuloperitonitis. PMID- 2243041 TI - Cardiac arrhythmias identified in horses with duodenitis/proximal jejunitis: six cases (1985-1988). AB - During a 3 1/2-year period, cardiac arrhythmias were identified in 6 of 67 horses diagnosed with duodenitis/proximal jejunitis (DPJ). Arrhythmias were detected by auscultation of irregular cardiac rhythm and subsequently were characterized by electrocardiographic evaluation. Arrhythmias included frequent second-degree atrioventricular block, ventricular ectopic depolarizations, and atrioventricular conduction disturbance. In 4 horses, arrhythmias resolved with recovery from the primary problem. One horse died suddenly 66 hours after admission, and another was euthanatized at 72 hours after admission. Clinical and laboratory data from horses with DPJ and cardiac arrhythmias (group 1) were compared with findings for horses with DPJ and without arrhythmias (group 2). Group-1 horses had significantly (P less than 0.05) higher serum bicarbonate concentration and serum creatine kinase activity. Normal sinus rhythm returned in all 4 group-1 horses that recovered from DPJ, suggesting a causal relationship between DPJ and the arrhythmias. Two group-1 horses were necropsied, and both had myocarditis. The cause of these lesions was not determined. PMID- 2243044 TI - Comments on a multiple-choice ethics examination. PMID- 2243045 TI - Informing health officials of reportable diseases. PMID- 2243043 TI - What is your diagnosis? Focal, ovoid, smooth-bordered, osseous proliferation compatible with an osteoma of the parietal bone. PMID- 2243046 TI - Comments on the specialty of internal medicine. PMID- 2243047 TI - Curbing hunger: veterinarians play role in global development. PMID- 2243048 TI - FDA-CVM asks for veterinary input on responsible compounding of drugs. PMID- 2243050 TI - US Army veterinarians stationed in Thailand. PMID- 2243049 TI - Veterinary biologic issues addressed by USDA. PMID- 2243051 TI - Make your voice heard. PMID- 2243052 TI - Blood transfusion: a historical review. PMID- 2243053 TI - Culture of endocrine pancreatic cells in protein-free, chemically defined media. AB - Cell suspensions prepared by collagenase digestion of pancreata obtained from 21.5-d-old rat fetuses were preincubated in RPMI medium containing 10% fetal bovine serum (FBS), to ensure cell adhesion. Twenty hours later, this medium was replaced by a chemically defined medium. Dulbecco's modified Eagle's (DME)-F12 was used alone or supplemented with various combinations of transferrin, sodium selenite, or Ultroser G. The evolution of the culture and the islet ultrastructure were similar in defined and serum-containing media. However, in the defined medium, the neoformed islets seemed less numerous, and the fibroblast layer less dense, when compared to the RPMI + 10% FBS control medium. At Day 7, in defined media, the total insulin content per dish was half that of control cultures. None of the tested additives improved the yield of the cultures. The fractional insulin release per day was elevated in defined media. In subsequent incubations, glucose and leucine stimulated insulin release in a way characteristic of these cells of fetal origin. The labeling index of islet cells cultured in DME-F12 reached 10.7%, which is not far from that observed in RPMI + 10% FBS. Such a defined medium is useful to study B cell physiology, avoiding the possible interaction of serum components with substances to be tested. PMID- 2243054 TI - Culture of isolated rat hepatocytes after prolonged storage on ice--a better use of cell resources. PMID- 2243055 TI - HBL-100 cells do not secrete casein and lack prolactin and estradiol receptors. PMID- 2243056 TI - Co-culture of two-cell rat embryos on cell monolayers. AB - Monolayers of 2 different populations of uterine cells and of fetal fibroblasts were evaluated for the support of rat embryo development in vitro. Compared to controls, cultures performed in Earle's buffered saline solution (EBSS) alone, the cleavage rate of 2-cell embryos to the 4-cell stage was significantly increased when the embryos were cocultured for 24 h with mixed uterine stromal and myometrial cells (70.7 vs. 56.0%; P less than 0.01). Coculture of 2-cell embryos with either uterine epithelial-stromal or stromal-myometrial cells in medium TC 199 (M199) for 24 h significantly increased the cleavage rate to the 4 cell stage compared to controls in the same medium (respectively, 78.3 and 77.6 vs. 49.9%; P less than 0.01). The development was not improved when fibroblasts were used as feeder cells. After 48 h, the proportion of 4-cell embryos showing cellular fragmentation was significantly decreased in the presence of either epithelial-stromal or stromal-myometrial cells in M199 compared to controls (respectively, 18.4 and 20.0 vs. 43.8%; P less than 0.01). Coculture in EBSS or with fibroblasts failed to prevent embryo degeneration. In one coculture with stromal-epithelial cells in M199, 6/11 embryos proceeded beyond the 4-cell stage, two of them reaching the 8-cell stage. No embryo developed beyond that stage in our study. Although considerable efforts remain necessary to achieve further growth, these results suggest that coculture offers promise as a means of supporting the in vitro development of rat embryos. PMID- 2243057 TI - Establishment of a macrophagelike cell line derived from U-937, human histiocytic lymphoma, grown serum-free. AB - A human macrophagelike cell line which grows in serum-free medium was established from a histiocytic lymphoma cell line, U-937. U-937 cells failed to differentiate into macrophagelike cells in serum-free medium plus 12-O-tetradecanoyl phorbol 13 acetate (TPA). Fibronectin and albumin in serum were necessary for differentiation of U-937 cells into macrophagelike cells in enriched RDF medium supplemented with insulin, transferrin, ethanolamine, selenite, egg yolk lipoprotein (eRDF-ITESL medium). The established cell line exhibited several characteristic properties of macrophage such as nitroblue tetrazolium reduction, phagocytic and alpha-naphthylbutyrate-esterase activities, and tumor necrosis factor and interleukin 1 production. At present the cells have been continuously maintained in eRDF-ITESL medium through over 150 passages. PMID- 2243058 TI - Long-term maintenance of primary myogenic cultures on a reconstituted basement membrane. AB - We describe a simple technique for maintaining highly contractile long-term chicken myogenic cultures on Matrigel, a gel composed of basement membrane components extracted from the Engelbreth-Holm-Swarm mouse tumor. Cultures grown on Matrigel consist of three-dimensional multilayers of cylindrical, contracting myotubes which endure for at least 60 d without myotube detachment. A Matrigel substrate increases the initial plating efficiency but does not effect cell proliferation. Large-scale differentiation in cultures maintained on Matrigel is delayed by 1 to 2 d, compared to cultures grown on gelatin-coated dishes. Long term maintenance on Matrigel also results in increased expression of the neonatal and adult fast myosin heavy chain isoforms. Culturing of cells on a Matrigel substrate could thus facilitate the study of later events of in vitro myogenesis. PMID- 2243059 TI - In vitro culture of tissue from the tunicate Styela clava. AB - Pharyngeal explants and circulatory hemocytes from the tunicate Styela clava were cultured in a medium containing tunicate plasma, artificial seawater, RPMI 1640, and antibiotics. Pharyngeal tissue remained viable and proliferated for up to 72 d in vitro. Proliferative activity maintained the pool of hemocytes within explants and facilitated the migration of pharyngeal hemocytes from explants into culture supernatants. The diversity of morphologically distinct cell types within the hemocyte pool of pharyngeal cultures indicated that cell division was followed by regulated differentiation. In contrast to pharyngeal cultures, suspensions of circulatory hemocytes did not survive for prolonged periods in vitro. Proliferative activity could not be detected in circulatory hemocyte cultures. These results are discussed in terms of the differentiation state of hemocytes and the efficacy of culture conditions. PMID- 2243060 TI - Characterization of malignant mesenchymal cell line (UISO-RS-3) derived from a human rhabdomyosarcoma and inhibition by pharmacologic doses of estrogen. AB - A new tumor cell line has been established from a malignant pleural effusion in a 28-yr-old female patient with a primary alveolar rhabdomyosarcoma of the left buttock. The in vitro and in vivo growth characteristics, morphologic features, abnormal karyotype, and immunohistochemical staining pattern indicate that this cell line is comprised of primitive malignant mesenchymal cells derived from a human rhabdomyosarcoma. Receptor studies done on tumors grown in male athymic mice revealed a single class of high affinity saturable cytoplasmic estrogen receptor (Bmax 2.6 fm/mg cytosol protein, Kd 0.34 nM). Likewise, sucrose density gradient analysis demonstrated specific low-capacity, high-affinity estradiol binding predominately in the 8S region. Cell growth in monolayer culture and on soft agar in the presence of estradiol was inhibited by pharmacologic concentrations of estradiol in a dose-responsive manner compared with control. We describe a newly characterized malignant mesenchymal cell line derived from an alveolar rhabdomyosarcoma that is inhibited by pharmacologic doses of estradiol in vitro. These findings suggest further investigation into the mechanism(s) of this estrogen-induced inhibition in rhabdomyosarcomas. PMID- 2243061 TI - Long ultradian rhythms in red blood cells and ghost suspensions: possible involvement of cell membrane. AB - Oscillations in glyceraldehyde-3-phosphate dehydrogenase (GAPD) and glucose-6 phosphate dehydrogenase (G6PD) activities were recorded in suspensions of intact human red blood cells (RBCs) exposed to various light regimens. The periods of these oscillations, defined as "long ultradian," ranged between 13 and 18 h regardless of light regimen. The patterns of enzymatic activities were the same when assayed at each time point, in full hypotonic hemolysates, and membrane-free hemolysates. However, if hemolysates were prepared by sonication the activity pattern did not exhibit significant oscillations and the activity was higher than that recorded in hypotonic hemolysates. The observed rhythms may reflect a time dependent attachment and detachment of enzyme molecules from cell membrane, suggesting that at the bound state the enzyme molecules are (temporarily) inactive. Oscillations with similar long ultradian periods were also observed in Ca++ concentration of suspended RBCs and in the binding of Ca++45 to human RBC ghosts. Treatment of the RBCs with A2C or Diamide before the preparation of the ghosts changed or distorted the rhythmic pattern of Ca++45 binding. These results point to the role of the membrane in processing the long ultradian oscillations. The relation between this type of oscillations to circadian rhythm is discussed. PMID- 2243062 TI - Influence of initial collagen and cellular concentrations on the final surface area of dermal and skin equivalents: a Box-Behnken analysis. AB - Our laboratory has been involved in finding optimal conditions for producing dermal and skin equivalents. As an original approach, a Box-Behnken experimental design was used to study the effects of the initial collagen and fibroblast concentrations and the initial gel thickness on the contraction of dermal and skin equivalents. The final surface area of dermal equivalent varied significantly with the initial concentration of collagen and fibroblast, whereas the initial thickness of gel had no appreciable effect on the contraction of the dermal equivalent. When keratinocytes were grown on these dermal equivalents they produced a very severe contraction, to an extent that all skin equivalents had a similar final surface area. This severe contraction was independent of collagen and fibroblast concentrations. Models for the prediction of the final percentage contraction of dermal and skin equivalents as a function of the initial concentration of collagen, the logarithm of fibroblast concentration, and the initial gel thickness were obtained and analyzed. Keratinocytes grown at the lowest seeding density did not contract the equivalents. However, histologic analysis has shown an incomplete coverage by these cells of the equivalents. The extensive contraction of the skin equivalent presenting adequate morphology is a major drawback toward its clinical utilization for burn wound coverage. PMID- 2243064 TI - A medium-format photographic protocol to aid in the management of dysplastic nevi syndrome. PMID- 2243063 TI - Inhibition of psoriatic cell proliferation in in vitro skin models by amiprilose hydrochloride. AB - Amiprilose hydrochloride, a 3-substituted glucose derivative, was found to inhibit the proliferation of human fibroblasts and keratinocytes originating from psoriatic lesions. Fibroblasts and keratinocytes were obtained from skin biopsies of normal donors, and from the biopsies of active/involved and uninvolved sites of psoriatic donors. The cells were cultured as monolayers or as components of tissue equivalent models. Keratinocytes and fibroblasts originating from biopsies of psoriatically involved areas were shown to proliferate at a significantly higher rate than those derived from uninvolved areas. The antiproliferative effect of amiprilose hydrochloride was not observed with normal keratinocytes or fibroblasts from the skin of healthy donors or from uninvolved areas of psoriatic donors. Amiprilose hydrochloride was not cytotoxic to any of these cells at levels below 0.1%. The combination of the low cytotoxicity and the selective antiproliferative effect indicates that this compound may be a useful antipsoriatic agent. The use of monolayer cultures and tissue equivalent models in this study illustrates the utility of such a progressive strategy in the evaluation of potential topical pharmaceuticals. PMID- 2243065 TI - Louis Schmidt award presented to Raymond E. Lund, RBP, FBPA. PMID- 2243066 TI - H. Paul Newman, RBP, FBPA receives Creer award. PMID- 2243067 TI - The redesigned Advanced Biomedical Photographic Communications program at Rochester Institute of Technology. PMID- 2243068 TI - Check your references or rediscovering the wheel. PMID- 2243069 TI - Computer-assisted calculation of film processing solution replenishment rates. PMID- 2243070 TI - The development of a photogrammetry service at the Royal Children's Hospital, Melbourne. PMID- 2243071 TI - RBP #1: an interview with Howard E. Tribe. Interview by Robert Turner. PMID- 2243072 TI - The production of one-piece, full-color scientific displays. PMID- 2243073 TI - Treatment of asthma: a comprehensive approach. PMID- 2243074 TI - Chemoprophylaxis in asthma. PMID- 2243075 TI - Environmental controls and immunotherapy in the treatment of chronic asthma. PMID- 2243076 TI - Asthma in New Zealand children. PMID- 2243077 TI - The pattern of skin test reactivity to aeroallergens in asthmatic children in Riyadh. PMID- 2243078 TI - Minimum substrate sequence for signal peptidase I of Escherichia coli. AB - The minimum substrate sequence recognized by signal peptidase I (SPase I or leader peptidase) was defined by measuring the kinetic parameters for a set of chemically synthesized peptides corresponding to the cleavage site of the precursor maltose binding protein (pro-MBP). The minimum sequence of a substrate hydrolyzed by SPase I at a measurable rate was the pentapeptide Ala-Leu-Ala decreases Lys-Ile. The rates of hydrolysis of this substrate, however, were several hundred-fold lower than those observed for the maturation of MBP in Escherichia coli, suggesting that in addition to these minimal sites involved in recognition, other features of pro-MBP are also needed for the optimal rate of signal peptide cleavage by SPase I. One parameter may be the length of the polypeptide chain. Studies of the synthetic peptides showed that decreasing the length of the polypeptide chain of substrates decreased the substrate efficiency measured as kcat/Km. However, in one case a decrease in the length of a peptide corresponding to -7 to +3 positions of pro-MBP to a nonapeptide (-7 to +2) increased the substrate efficiency by about 900-fold. The nonapeptide is the most efficient substrate for the enzyme in vitro so far reported. It is speculated that better peptide substrates are the ones which are able to adopt folded structures. PMID- 2243079 TI - Immunochemical analysis of the exposure of high mobility group protein 14 and 17 surfaces in chromatin. AB - Antisera were elicited against synthetic peptides corresponding either to regions common to all members of the high mobility group 14 and 17 protein family protein or to distinct domains of the HMG-14 or HMG-17 subgroup. The antisera were used to probe the accessibility of various HMG domains in chromatin. Competitive enzyme-linked immunosorbent assays indicate that the central region of the proteins, which contains their DNA binding domain and is positively charged, is exposed to a smaller degree than the C-terminal region of the proteins, which has a net negative charge. The C-terminal regions of the HMG-14 and HMG-17 proteins are exposed and available to interact with other proteins. PMID- 2243080 TI - Isolation of subtilisin pro-sequence mutations that affect formation of active protease by localized random polymerase chain reaction mutagenesis. AB - In order to analyze the role of the pro-sequence in folding of the alkaline serine protease subtilisin, localized random mutagenesis using the polymerase chain reaction with Taq DNA polymerase was employed to obtain mutations in the pro-sequence which prevent production of active protease. The unique aspect of this procedure is that random mutations can be easily generated in vitro over large but defined regions of a specific gene. The method was applied to a 458 base pair fragment encompassing the coding region of the pro-sequence of subtilisin, a region of the protein which has been shown to be required for proper folding. Protease-deficient mutants containing a variety of amino acid substitutions were isolated with a frequency of 4.3%. From analysis of these mutants, four independent amino acid substitution mutations in the pro-sequence were identified. The present results demonstrate that polymerase chain reaction is an efficient and simple method for obtaining random mutations within a localized region of a given gene. PMID- 2243081 TI - HIV-1 tat gene induces tumor necrosis factor-beta (lymphotoxin) in a human B lymphoblastoid cell line. AB - The tat protein from human immunodeficiency virus type 1 (HIV-1) activates viral gene expression and is essential for HIV replication in vitro. It has also been shown that the tat gene product specifically inhibits antigen-induced proliferation of human peripheral blood lymphocytes. In order to understand the growth and immunomodulatory roles of HIV-1 tat, we have examined the effect of the tat gene on the expression of tumor necrosis factors in a human B lymphoblastoid cell line (Raji). We report here that the HIV-1 tat gene introduced into Raji cells by retroviral-mediated transformation induces production of tumor necrosis factor-beta (TNF-beta). The tat-mediated induction of TNF-beta seems to be both at the transcriptional and post-transcriptional levels because, concurrent with a 30-fold increase in the levels of TNF-beta protein, an approximate 8-fold increase in mRNA was observed in tat-transformed Raji cells. It is recently reported that tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients (Ensoli, B., Barillari, G., Salahuddin, S.Z., Gallo, R.C., and Wong-Staal, F. (1990) Nature 345, 84-86). Since TNF has been shown to function as a growth factor for several cell types, our results showing induction of TNF-beta by tat indicate the possibility that a growth-stimulatory role of HIV-1 tat on Kaposi's sarcoma cells is mediated through TNF-beta. PMID- 2243082 TI - Alpha-dendrotoxin acceptor from bovine brain is a K+ channel protein. Evidence from the N-terminal sequence of its larger subunit. AB - High affinity acceptors for alpha-dendrotoxin, a selective probe for certain fast activating voltage-dependent K+ channels, were purified approximately 4,000-fold from synaptic plasma membranes of bovine cerebral cortex. Although the preparation possessed a low content of high affinity sites for beta-bungarotoxin, antagonism of alpha-dendrotoxin binding by the latter required high concentrations; this indicates that more than one acceptor subtype has been purified. After deglycosylation of the acceptor, the sizes of its subunits were determined electrophoretically to be Mr 65,000 and Mr 39,000. Solid phase microsequencing of these isolated subunits showed that the smaller one had a blocked N terminus, but the Mr 65,000 protein gave a sequence of 27 residues. This is virtually identical to the N-terminal sequence deduced from cDNA of RCK 5, a K+ channel protein from rat brain known to be susceptible to alpha dendrotoxin. This first report on the partial sequence of any K+ channel protein confirms that the extensive information acquired to date on the alpha-dendrotoxin acceptors is pertinent to functional neuronal K+ channels. PMID- 2243084 TI - Hormone-free mouse glucocorticoid receptors overexpressed in Chinese hamster ovary cells are localized to the nucleus and are associated with both hsp70 and hsp90. AB - In this work, we examine the cellular localization and protein interactions of mouse glucocorticoid receptors that have been overexpressed in Chinese hamster ovary (CHO) cells (Hirst, M. A., Northrop, J. P., Danielsen, M., and Ringold, G. M. (1990) Mol. Endocrinol. 4, 162-170). We demonstrate that wild-type unliganded mouse glucocorticoid receptor, which is expressed in CHO cells to a level approximately 10 times that of L cells, is localized entirely to the nucleus by indirect immunofluorescence with the BuGR antireceptor monoclonal antibody. Overexpressed receptors that have either no hormone binding activity or no DNA binding activity because of point mutations also localize to the nucleus, providing genetic proof that the nuclear localization cannot reflect a steroid mediated shift of the receptor from the cytoplasm to the nucleus and that DNA binding activity is not required for nuclear localization. Like unliganded progesterone receptors, which also associate in a loosely bound "docking" complex with the nucleus, the mouse glucocorticoid receptor overexpressed in CHO cells is associated with both hsp90 and hsp70. This is in contrast to the untransformed mouse glucocorticoid receptor in L cell cytosol, which is associated with hsp90 but not hsp70. The difference in hsp70 association between cell types could reflect overexpression of the receptor in CHO cells. However, like receptors in CHO cells selected for very high levels of overexpression, receptors in CHO cells selected for an intermediate level of receptor expression that is comparable to that of L cells are also bound to hsp70. This observation argues against an explanation of hsp70 association based purely on receptor overexpression, and we speculate that association of the unliganded glucocorticoid receptor with hsp70 might be a consequence of its nuclear localization in the CHO cells. Although there are differences between the mouse receptor in CHO cells and L cells, the nuclear localization signal of the untransformed mouse receptor reacts equivalently with the AP64 antibody against NL1 in cytosols prepared from both cell types. PMID- 2243083 TI - Sorting of peroxisomal membrane protein PMP47 from Candida boidinii into peroxisomal membranes of Saccharomyces cerevisiae. AB - A gene encoding PMP47, a peroxisomal integral membrane protein of the methylotrophic yeast Candida boidinii, was isolated from a genomic library. DNA sequencing of PMP47 revealed an open reading frame of 1269 base pairs capable of encoding a protein of 46,873 Da. At least two membrane-spanning regions in the protein are predicted from the sequence. Since the 3 amino acids at the carboxyl terminus are -AKE, PMP47 lacks a typical peroxisomal sorting signal. No significant similarities in primary structure between PMP47 and known proteins were observed, including PMP70, a rat peroxisomal membrane protein whose sequence has recently been reported (Kamijo, K., Taketani, S., Yokota, S., Osumi, T., and Hashimoto, T. (1990). J. Biol. Chem. 265, 4534-4540). In order to study the import and assembly of PMP47 into peroxisomes by genetic approaches, the gene was expressed in the yeast Saccharomyces cerevisiae. When PMP47 was expressed in cells grown on oleic acid to induce peroxisomes, the protein was observed exclusively in peroxisomes as determined by marker enzyme analysis of organelle fractions. Most of the PMP47 co-purified with the endogenous peroxisomal membrane proteins on isopycnic sucrose gradients. Either in the native host or when expressed in S. cerevisiae, PMP47 was not extractable from peroxisomal membranes by sodium carbonate at pH 11, indicating an integral membrane association. These results indicate that PMP47 is competent for sorting to and assembling into peroxisomal membranes in S. cerevisiae. PMID- 2243085 TI - "Suicide" inactivation of thromboxane A2 synthase. Characteristics of mechanism based inactivation with isolated enzyme and intact platelets. AB - "Suicide" inactivation occurs during catalysis by thromboxane synthase. Loss of enzymatic activity, accompanying thromboxane B2 formation, was proportional to the substrate concentration. Inactivation was directly related to product formation: for several different experimental protocols 50% loss of thromboxane synthase activity corresponded with formation of 454 +/- 79 ng of thromboxane B2/mg protein. The time course of inactivation was pseudo-first-order and obeyed saturation kinetics. Inactivation (KI) and first-order rate constants (ki) were 18 microM and 0.18 s-1 for prostaglandin H2. Prostaglandin H1, a poor substrate for turnover, was also a site-directed inactivator with KI = 28 microM and ki = 0.09 s-1. Competitive inhibitors, typified by U63557a and U46619, preserved the enzyme activity by slowing the rate of inactivation from 0.18 to 0.05 s-1. Loss of the hemoprotein Soret absorbance did not correlate quantitatively or temporally with the loss of thromboxane synthase activity. A similar, irreversible inactivation accompanied thromboxane formation by intact platelets. Loss of activity was proportional to substrate concentration and catalytic activity. For a pool of 25 separate donors, thromboxane synthase activity declined exponentially as a function of thromboxane B2 formation: 50% loss of activity corresponded to 23 ng of thromboxane B2/10(7) platelets. The data conform to criteria for a specific, mechanism-based process in which thromboxane synthase participates in two parallel reactions, one leading to thromboxane formation and the other to suicide inactivation. The specific, rather than indiscriminate, nature of the process, and its occurrence in intact platelets may have implications for the cell biology of thrombosis. Depletion of thromboxane synthase activity may be a factor in the choice and effectiveness of antithrombotic agents. PMID- 2243086 TI - Protein factors that bind to the murine 2',5'-oligoadenylate synthetase ME-12 gene 5' upstream regulatory region. AB - The murine 2',5'-oligoadenylate synthetase ME-12 gene regulatory region AB forms six complexes with protein factors in murine BALB/c 3T3 cells as demonstrated by the mobility shift electrophoresis assay under the reaction conditions used. The complexes, designated C1-C6 in order of their decreasing electrophoretic mobility, showed three distinctive specificities with regulatory region AB, element A, and element B as probes or competing DNA: 1) C1 is region AB-specific (this complex did not form with either element A or B used alone or as a mixture); 2) C5 formed both with element A and element B; 3) C2, C3, C4, and C6 formed with element B, but not A. The protein factors that give rise to these complexes show differential DNA binding activities in various buffer solutions at different pH values. The C4-forming protein factor is the interferon (IFN) alpha/beta-stimulated response factor (ISRF) which shows element B specificity. It preexists in the cytoplasm. ISRF appears to be complexed to an inhibitor (ISRFI) in the cytoplasm and to dissociate from the inhibitor and to translocate into the nucleus upon treatment of cells with IFN-alpha/beta. We propose that IFN alpha/beta treatment of BALB/c 3T3 can trigger at least two events: 1) loosening of a tight inhibitor-ISRF complex with the release of free ISRF; this may be mediated via phosphorylation of ISRF or ISRFI; 2) translocation of ISRF into the nucleus and binding to the enhancer element B, which results in the activation of 2',5'-oligoadenylate synthetase gene expression. PMID- 2243087 TI - The effect of phosphate and calcium on force generation in glycerinated rabbit skeletal muscle fibers. A steady-state and transient kinetic study. AB - The effect of varying concentrations of Pi and Ca2+ on isometric force and on the rate of force development in skinned rabbit psoas muscle fibers has been investigated. Steady-state results show that the three parameters that define the force-pCa relation (Po, pK, and n) all vary linearly with log [Pi]. As [Pi] increases, Po and pK decrease while n increases. The kinetics of force generation in isometrically contracting fibers were studied by laser flash photolysis of caged phosphate. The observed rate of the resulting tension transient, kPi, is 23.5 +/- 1.7 s-1 at 10 degrees C, 0.7 mM Pi, and is independent of [Ca2+] over the range pCa 4.5-7.2. By contrast, kTR, the rate of tension redevelopment following a period of isotonic shortening, is sensitive to [Ca2+] and is slower than kPi (kTR = 13.6 +/- 0.2 s-1 at pCa 4.5, 0.7 mM Pi). The results show that [Ca2+] does not directly affect the Pi release or force-generating steps of the cross-bridge cycle and show that the observed rate of force development depends on how the measurement is made. The data can be interpreted in terms of a model in which strong cross-bridges activate the thin filament, this activation being modulated by Ca2+ binding to troponin. PMID- 2243088 TI - Mouse beta thalassemia, a model for the membrane defects of erythrocytes in the human disease. AB - The present study describes the pathophysiology, at the cellular level, of the mouse beta thalassemia and shows the pertinence of this model for the human disease. The homozygous state of mouse beta thalassemia is characterized by a clinical syndrome similar to the human beta thalassemia intermedia, but it cannot be explained by the small deficiency in beta chain synthesis. The small pool of unpaired and soluble alpha chains present in mouse reticulocytes contrasts with the large amount of insoluble alpha chains in erythrocytes which is induced by the high instability of mouse alpha chains and the absence of significant proteolysis. The amount of insoluble alpha chains associated with red cell ghosts is similar in human and mouse disease of similar severity. The study of membrane protein defects showed a decreased amount of spectrin (alpha and beta chains) and dramatic changes in the distribution of the most reactive thiol groups of membrane proteins. These results were similar to that previously described in the human disease (Rouyer-Fessard, P., Garel, M. C., Domenget, C., Guetarni, D., Bachir, D., Colonna, P., and Beuzard, Y. (1989) J. Biol. Chem. 264, 19092-19098). Abnormal density distribution curves of erythrocytes and oxidant-induced lysis of red blood cells used as functional tests were similar in the human and mouse beta thalessemia. We conclude from the present study that 1) mouse beta thalassemia is an excellent model for the membrane defects occurring in the human disease; 2) disease expression is not the reflection of the globin chain unbalance only nor of the soluble pool of alpha hemoglobin chain but mainly is a reflection of insoluble alpha chains; and 3) the rate of proteolysis and instability of alpha chains are important factors which must be taken into consideration in the pathophysiology and the clinical heterogeneity of the disease. PMID- 2243089 TI - Biochemical study of a recombinant soluble interleukin-2 receptor. Evidence for a homodimeric structure. AB - A truncated soluble form of the human interleukin-2 receptor p55 chain (T-S-IL 2R) was expressed to high levels in RODENT (mammalian) cells and affinity purified. Its biochemical behavior was analyzed by polyacrylamide gel electrophoresis (PAGE), gel filtration, and sucrose gradient centrifugation. It migrated as a single 40-kDa band on sodium dodecyl sulfate-PAGE (reducing or nonreducing conditions), whereas it ran as a 80-kDa component on native PAGE or as a 86-kDa component on gel filtration. The combination of gel filtration and density gradient sedimentation gave a Stokes radius of 4.0 nm and a sedimentation coefficient of 3.72 S. The deduced molecular mass was 67 kDa, and the fractional ratio was 1.516. These data therefore indicated that the T-S-IL-2R was secreted as an homodimer of two noncovalently associated 40-kDa subunits. Cross-linking experiments using bifunctional reagents enabled the materialization of the dimeric structure on sodium dodecyl sulfate-PAGE. Stoichiometric binding studies using two monoclonal antibodies (mAbs 33B3.1 and 11H2) reacting with separate epitopes on the p55 chain also strongly supported the dimeric structure. Indeed, there was one binding site for the 33B3.1 mAb (and Fab fragment) per T-S-IL-2R 40 kDa subunit, whereas the 11H2 mAb (or Fab fragment) could bind only half a site per subunit, a result which could only be explained when assuming more than one subunit for the native T-S-IL-2R. Soluble interleukin-2 receptor species were also purified from culture supernatants of either L cells transfected with the full-length p55 cDNA or a normal alloreactive T cell clone. Similar biochemical behavior and reactivities with the two mAbs were found. Finally, cell-surface p55 chains expressed either by pgL21 or 4AS cells bound the 33B3.1 and 11H2 mAbs in a 2:1 ratio, suggesting that the p55 chains are also associated as homodimers when imbedded in the membrane. PMID- 2243090 TI - Stereoselectivity of lipases. I. Hydrolysis of enantiomeric glyceride analogues by gastric and pancreatic lipases, a kinetic study using the monomolecular film technique. AB - In the present study, porcine pancreatic lipase, rabbit gastric lipase, and human gastric lipase stereospecificity toward enantiomeric glyceride derivatives was kinetically investigated using the monomolecular film technique. Pseudoglycerides such as enantiomeric 1(3)-alkyl-2,3(1,2)-diacyl-sn-glycerol, enantiomeric 1(3) alkyl-2-acyl-sn-glycerol, or enantiomeric 1(3)-acyl-2-acylamino-2-deoxy-sn glycerol were synthesized in order to assess the lipase stereoselectivity during the hydrolysis of either the primary or the secondary ester position of these glycerides analogues. The cleaved acyl moiety was the same in both enantiomers, thereby excluding the possibility of effects occurring due to fatty acid specificity. We observed a porcine pancreatic lipase sn-3 stereoselectivity when using the enantiomeric 1(3)-alkyl-2-acylamino-2-deoxy-sn-glycerol (diglyceride analogue) which contrasted with the lack of stereoselectivity observed when using the enantiomeric 1(3)-alkyl-2,3(1,2)-diacyl-sn-glycerol (triglyceride analogue). The gastric lipases, in contrast to the pancreatic lipase, preferentially catalyze the hydrolysis of the primary sn-3 ester bond of the enantiomeric monoakyl-diacyl pair tested. From these kinetic data, high hydrolysis rates and no chiral discrimination were observed in the case of rabbit gastric lipase, whereas low rates and a clear chiral discrimination was noticed in the case of human gastric lipase during hydrolysis of the acyl chain from the secondary ester bond of 1(3)-alkyl-2-acyl enantiomers. It is particularly obvious that in the case of human gastric lipase decreasing the lipid packing increases the lipase sn 3 stereopreference during hydrolysis of the primary ester bond of the enantiomeric 2-acylamino derivatives (diglyceride analogue). PMID- 2243091 TI - Stereoselectivity of lipases. II. Stereoselective hydrolysis of triglycerides by gastric and pancreatic lipases. AB - In the present study, porcine pancreatic lipase, rabbit gastric lipase, and human gastric lipase stereospecificity toward chemically alike, but sterically nonequivalent ester groups within one single triglyceride molecule was investigated. Lipolysis reactions were carried out on synthetic trioctanoin or triolein, which are homogenous, prochiral triglycerides, chosen as models for physiological lipase substrates. Diglyceride mixtures resulting from lipolysis were derivatized with optically active R-(+)-1-phenylethylisocyanate, to give diastereomeric carbamate mixtures, which were further separated by high performance liquid chromatography. Resolution of diastereomeric carbamates gave enantiomeric excess values, which reflect the lipases stereobias and clearly demonstrate the existence of a stereopreference by both gastric lipases for the sn-3 position. The stereoselectivity of human and rabbit gastric lipases, expressed as the enantiomeric excess percentage, was 54% and 70% for trioctanoin and 74% and 47% for triolein, respectively. The corresponding values with porcine pancreatic lipase were 3% in the case of trioctanoin and 8% in that of triolein. It is worth noting that rabbit gastric lipase, unlike human gastric lipase, became more stereoselective for the triglyceride with shorter acyl chains (trioctanoin). This is one of the most striking catalytic differences observed between these two gastric lipases. PMID- 2243092 TI - Structural and functional analysis of the human thymidylate synthase gene. AB - The complete nucleotide sequence of the human thymidylate synthase (TS) gene was determined. The biologically active unit spans about 16 kilobase pairs (kbp) and is composed of seven exons and six introns. The promoter region and the major transcriptional start sites were located within about 400 base pairs (bp) and 160 180 bp, respectively, upstream from the ATG initiation codon. A minigene consisting of a 5'-flanking sequence of about 4 kbp, a coding sequence of about 1.7 kpb was sufficient for cell cycle-dependent expression of TS when introduced into a TS-deficient mutant of rodent cells. The 5'-flanking region does not contain a "TATA," "CAAT," or the consensus sequence for Sp1 binding (GC box), whereas intron 1 contains three GC boxes. The gene is G + C-rich and the CpG-rich region extends from 5'-flanking region to intron 1. These sequence characteristics were compared with those of the mouse TS gene and other cell cycle-regulated genes. PMID- 2243093 TI - Cellular factors involved in transcription and Tax-mediated trans-activation directed by the TGACGT motifs in human T-cell leukemia virus type I promoter. AB - Human T-cell leukemia virus type I (HTLV-I) encodes a 40-kDa nuclear protein, Tax, which stimulates transcription from three 21-base pair (bp) repeats in its U3 region. Tax trans-activation is mediated via cellular factors that interact with the TGACGT motifs in the 21-bp repeats. Gel mobility shift assay and UV cross-linking analysis show that two proteins of 52 and 46 kDa in size bind the 21-bp repeat specifically. Base substitutions in the TGACGT motif which abolished Tax trans-activation abrogated factor binding whereas the repeats containing mutations that did not affect Tax trans-activation supported factor binding as the wild-type repeat. The 52- and 46-kDa factors are present in human T-cell lines Jurkat and MT4 (HTLV-I transformed) and in HeLa cells but are undetectable in a human placental cell line JEG-3, which gave a reduced level of trans activation. JEG-3 extracts contain a distinct DNA binding activity that shows analogous sequence requirements as the 52- and 46-kDa proteins in interacting with the various 21-bp repeats. c-Jun and CREB (cAMP-responsive element binding factor) can stimulate transcription from HTLV-I long terminal repeats in JEG-3 cells. At least two copies of the 21-bp repeats are required for optimal trans activation by c-Jun and CREB. Most single point mutations in the TGACGT motif that abolished Tax trans-activation, however, did not affect c-Jun- or CREB directed transcriptional enhancement. These data indicate that many transcription factors including c-Jun and CREB exert stimulatory effects on HTLV-I transcription although they do not directly respond to Tax. The 52- and 46-kDa cellular proteins most likely are involved directly in Tax-mediated trans activation, and they are tentatively named Tax activation factors I and II, respectively. PMID- 2243094 TI - Studies on the mechanism of oxidative phosphorylation. ADP promotion of GDP phosphorylation. AB - The process of ATP or GTP synthesis by bovine heart submitochondrial particles involves the binding of ADP or GDP to 3 exchangeable sites I, II, and III, and only upon substrate occupation of site III does rapid ATP or GTP synthesis take place. The dissociation constants determined for ADP were KADPI less than or equal to 10(-8) M, KADPII approximately 10(-7) M, and KADPIII (equivalent to apparent KADPm), approximately 3 x 10(-6) M in the low Km mode and KADPIII approximately 150 x 10(-6) M in the high Km mode. For GDP, these constants were KGDPI approximately 10(-6)-10(-5) M, KGDPII approximately 10(-4) M, and KGDPIII approximately 10(-3) M when NADH was the respiratory substrate (Matsuno-Yagi, A., and Hatefi, Y. (1990) J. Biol. Chem. 265, 82-88). Because of its low affinity for the above binding sites, GDP at micromolar concentrations does not lead to GTP synthesis. However, as shown in this paper, micromolar [GDP] undergoes phosphorylation in the presence of micromolar concentrations of ADP. Under these conditions, both ATP and GTP are synthesized. GDP inhibits ATP synthesis with KGDPi congruent to 7 microM, while ADP promotes GTP synthesis in a reaction that requires inorganic phosphate (apparent KPim = 2-3 mM) and is inhibited by uncouplers and inhibitors of the ATP synthase complex. The ADP-promoted GTP synthesis exhibited an "apparent" KGDPm = 4 microM and an "apparent" Vmax = 11 nmol of GTP (min.mg of protein)-1. These results were interpreted to mean that (a) micromolar [ADP] occupies sites I and II, allowing site III to bind and phosphorylate GDP, and (b) the KGDPm and Vmax calculated under these conditions represent values for the low Km-low Vmax mode of GTP synthesis, which in the absence of ADP is not detectable because of the positive cooperativity phase of GTP synthesis with the high KGDPII approximately 10(-4) M. PMID- 2243095 TI - Intracellular Na+ kinetically interferes with the rotation of the Na(+)-driven flagellar motors of Vibrio alginolyticus. AB - To understand the mechanism of Na+ movement through the force-generating units of the Na(+)-driven flagellar motors of Vibrio alginolyticus, the effect of intracellular Na+ concentration on motor rotation was investigated. Control cells containing about 50 mM Na+ showed good motility even at 10 mM Na+ in the medium, i.e. in the absence of an inwardly directed Na+ gradient. In contrast, Na(+) loaded cells containing about 400 mM Na+ showed very poor motility at 500 mM Na+ in the medium, i.e. even in the presence of an inwardly directed Na+ gradient. The membrane potential of the cells, which is a major driving force for the motor under these conditions, was not detectably altered, and consistently with this, Na(+)-coupled sucrose transport was only partly reduced in the Na(+)-loaded cells. Motility of the Na(+)-loaded cells was restored by decreasing the intracellular Na+ concentration, and the rate of restoration of motility correlated with the rate of the Na+ decrease. These results indicate that the absolute concentration of the intracellular Na+ is a determinant of the rotation rate of the Na(+)-driven flagellar motors of V. alginolyticus. A simple explanation for this phenomenon is that the force-generating unit of the motor has an intracellular Na(+)-binding site, at which the intracellular Na+ kinetically interferes with the rate of Na+ influx for motor rotation. PMID- 2243096 TI - Dissociation of the DNA polymerase III holoenzyme beta 2 subunits is accompanied by conformational change at distal cysteines 333. AB - The beta subunit of DNA polymerase III holoenzyme is in a dimer-monomer equilibrium at physiological beta concentrations. Dissociation is accompanied by the fluorescence enhancement of a fluorophore attached to a unique sulfhydryl group of beta (Griep, M. A., and McHenry, C. S. (1988) Biochemistry 27, 5210 5215). Sequencing of the isolated tryptic peptides of beta revealed that the fluorescent maleimide group was attached to cysteine 333. The 2 residues, lysine 332 and glutamate 334, that flank this residue are hydrophilic and may place cysteine 333 on the surface of beta, explaining its high reactivity. Fluorescence energy transfer permitted us to locate the uniquely labeled cysteines 333 of beta at the distal ends of the beta dimer. When the beta dimer was dissociated to monomers, the accompanying alteration of the conformational state was reported by the fluorescein-5-maleimide (fluorescein)-labeled cysteines which were located far from the dimer interface. The carboxyl of fluorescein had a fluorescence pKa of 6.9 when beta was in its dimeric state. The pKa decreased by 0.3 pH unit upon dissociation to monomers and resulted in the fluorescence enhancement that was observed when the signal was monitored at constant pH. The adjacent glutamate 334 apparently increased the pKa of the attached fluorescein when beta was in its dimeric state. Movement of either the adjacent lysine 332 amino side chain to a closer position or glutamate 334 to a position further away could lower the pKa upon beta monomerization. Thus, beta undergoes a conformational change concomitant with dimer dissociation that was transmitted to the opposite ends of the beta dimer. The pKa of fluorescein attached to the distal cysteines was shifted, leading to greater ionization and enhanced fluorescence. PMID- 2243097 TI - Isolation and primary structure of PARP, a 24-kDa proline- and arginine-rich protein from bovine cartilage closely related to the NH2-terminal domain in collagen alpha 1 (XI). AB - A protein rich in proline and arginine (proline/arginine-rich protein (PARP] has been isolated from dissociative extracts of bovine nasal and articular cartilage, and its primary structure has been determined. The protein has 218 amino acids, giving a calculated protein Mr of 24,075. In nasal cartilage, this protein is in molar concentrations equivalent to 1/20-1/10 that of the link protein of cartilage proteoglycan aggregates. PARP has also been isolated from bovine articular cartilage, bovine fetal epiphysis, and nonossified human tarsal bones. PARP is similar to various collagen NH2-terminal domains. It is 49% identical to the NH2-terminal end of collagen alpha 1 (XI), 17% identical to the NC4 domain of collagen alpha 1 (IX), and 14% identical to the NC3 domain of collagen alpha 1 (XII). Four cysteines are conserved between type XI collagen and PARP, and these form two disulfide bonds. Two of the cysteines are also conserved between PARP and collagens IX and XII. The homology between the collagens and PARP makes it possible to speculate on the likely disulfide bond pattern in the collagen NH2 terminal domains. It is probable that PARP is a collagen fragment removed during processing in a manner analogous to chondrocalcin (the C-terminal propeptide of type II collagen). PMID- 2243098 TI - Disruption of active site interactions with pyridoxal 5'-phosphate and substrates by conservative replacements in the glycine-rich loop of Escherichia coli D serine dehydratase. AB - We have used site-directed mutagenesis to examine the function of three putative active site residues (C278, G279, and G281) of the vitamin B6 enzyme D-serine dehydratase. These residues lie in or adjacent to a conserved glycine-rich loop that is known to interact with the pyridoxal 5'-phosphate cofactor in several B6 enzymes and that resembles the GXGXXG loop of nucleotide-binding sites. The cofactor affinity, catalytic properties, and spectral properties (UV, CD, fluorescence, and 31P NMR) of alanine variants C278A, G279A, and G281A were measured as well as the susceptibility of each variant to thiol modification by 5,5'-dithiobis(2-nitrobenzoic acid). The specific thiols modified in each variant and wild type D-serine dehydratase were identified by amino acid sequencing of labeled tryptic peptides. C278A, G279A, and G281A displayed 10-, 33-, and 22-fold lower affinities for pyridoxal 5'-phosphate than did wild type D-serine dehydratase and turnover numbers with D-serine that were 50, 6, and 60% of normal, respectively. The introduction of a methyl side chain into G281 enhanced catalytic efficiency with the substrates D-threonine, D-allo-threonine, and L serine, whereas the methyl side chain at position 279 impaired catalysis of all substrates as well as cofactor affinity. The 31P NMR spectrum of D-serine dehydratase was minimally perturbed by the alanine substitutions, consistent with the view that neither G279 nor G281 interacts with the phosphate group of the cofactor (in contrast to the arrangement found in several other B6 enzymes). C311 was the single thiol modified by 5,5'-dithiobis(2-nitrobenzoic acid) in wild type D-serine dehydratase. Two normally inaccessible thiol groups, C233 and C278, were rendered susceptible to modification as a consequence of either G----A substitution, and modification of C278 was associated with inactivation of G279A and G281A. These observations suggest that small perturbations in the glycine rich loop induce conformational changes spanning a considerable area around the active site. PMID- 2243099 TI - Beta spectrin in human skeletal muscle. Tissue-specific differential processing of 3' beta spectrin pre-mRNA generates a beta spectrin isoform with a unique carboxyl terminus. AB - Spectrin, an important component of the mammalian erythrocyte membrane skeleton, is a heterodimeric protein with alpha and beta subunits of 280 and 246 kDa, respectively. Spectrin-like proteins have also been demonstrated in a wide variety of nonerythroid cells. To examine the hypothesis that nonerythroid beta spectrins may be encoded by the "erythroid" beta spectrin gene, we have isolated cDNA clones from a human fetal skeletal muscle library by hybridization to a previously described red cell beta spectrin cDNA. Detailed comparison of muscle and erythroid beta spectrin cDNAs has revealed sequence identity over the majority of their lengths, confirming that they are the product of the same gene. However, there is a sharp divergence in sequence at their 3' ends. A consequence of this divergence is the replacement of the carboxyl terminus of erythroid beta spectrin with a different, longer carboxyl-terminal domain in skeletal muscle. We hypothesize that tissue-specific differential polyadenylation leads to the selective activation of a donor splice site within the beta spectrin coding sequence, splicing downstream nonerythroid exons into the mature muscle beta spectrin mRNA. We predict that replacement, in nonerythroid cells, of the beta spectrin carboxyl terminus, known to participate in spectrin self-association and phosphorylation, has significant functional consequences. These data may explain previously reported nonerythroid beta spectrin isoforms that resemble red cell beta spectrin by immunochemical analysis. PMID- 2243100 TI - Characterization of human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase gene and its expression in mammalian cells. AB - Three beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD) catalyze the oxidative conversion of delta 5-3 beta-hydroxysteroids to the delta 4-3-keto configuration and is therefore essential for the biosynthesis of all classes of hormonal steroids, namely progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens. Using human 3 beta-HSD cDNA as probe, a human 3 beta-HSD gene was isolated from a lambda-EMBL3 library of leucocyte genomic DNA. A fragment of 3 beta-HSD genomic DNA was also obtained by amplification of genomic DNA using the polymerase chain reaction. The 3 beta-HSD gene contains a 5'-untranslated exon of 53 base pairs (bp) and three successive translated exons of 232, 165, and 1218 bp, respectively, separated by introns of 129, 3883, and 2162 bp. The transcription start site is situated 267 nucleotides upstream from the ATG initiating codon. DNA sequence analysis of the 5'-flanking region reveals the existence of a putative TATA box (ATAAA) situated 28 nucleotides upstream from the transcription start site while a putative CAAT binding sequence is located 57 nucleotides upstream from the TATA box. Expression of a cDNA insert containing the coding region of 3 beta-HSD in nonsteroidogenic cells shows that the gene encodes a single 42-kDa protein containing both 3 beta hydroxysteroid dehydrogenase and delta 5-delta 4-isomerase activities. Moreover, all natural steroid substrates tested are transformed with comparable efficiency by the enzyme. In addition to its importance for studies of the regulation of expression of 3 beta-HSD in gonadal as well as peripheral tissues, knowledge of the structure of the human 3 beta-HSD gene should permit investigation of the molecular defects responsible for 3 beta-HSD deficiency, the second most common cause of adrenal hyperplasia in children. PMID- 2243101 TI - Granulocytic differentiation of HL-60 cells is associated with increase of poly-N acetyllactosamine in Asn-linked oligosaccharides attached to human lysosomal membrane glycoproteins. AB - HL-60 cells were induced to differentiate into granulocytic cells by dimethyl sulfoxide, and structures of Asn-linked oligosaccharides attached to lysosomal membrane glycoproteins (lamp-1 and lamp-2) were elucidated before and after differentiation. Lamp-1 and lamp-2 were immunoprecipitated from the cells after labeling with radioactive sugars, and glycopeptides were prepared. The structures of glycopeptides obtained after serial lectin-affinity chromatography were elucidated by endo-beta-galactoside and methylation analysis. Glycopeptides bound to tomato lectin-Sepharose were found to be tetraantennary oligosaccharides that contain two or three poly-N-acetyllactosaminyl chains, of which one side chain contains three or more N-acetyllactosaminyl repeats, whereas those bound to Datura stramonium agglutinin-Sepharose were found to be tetraantennary oligosaccharides containing one or two short poly-N-acetyllactosaminyl side chains. Glycopeptides that were not bound to concanavalin A, tomato lectin, or D. stramonium agglutinin were found to be triantennary oligosaccharides with a negligible amount of poly-N-acetyllactosaminyl side chains. Comparison of Asn linked oligosaccharides from undifferentiated and differentiated HL-60 cells reveals the following features. First, the number of Asn-linked oligosaccharides containing poly-N-acetyllactosaminyl side chains increases dramatically with a concomitant decrease in less complex Asn-linked oligosaccharides after differentiation. Second, the number of poly-N-acetyllactosaminyl side chains per Asn-linked oligosaccharides increases significantly. These increases in poly-N acetyllactosamine were associated with increased activity of UDP-GlcNAc:beta-D Gal-beta 1----3-N-acetylglucosaminyltransferase "extension enzyme," a key enzyme in the formation of poly-N-acetyllactosamines. Furthermore, the increased amount of poly-N-acetyllactosamine in lamp-1 and lamp-2 resulted in longer half-lives of lamp-1 and lamp-2 in differentiated HL-60 cells. These results suggest strongly that the differentiation of HL-60 cells into more phagocytic cells is associated with an increase in the complexity of Asn-linked oligosaccharides attached to lysosomal membrane glycoproteins, which in turn may play a role in stabilizing lysosomes. PMID- 2243102 TI - The polylactosaminoglycans of human lysosomal membrane glycoproteins lamp-1 and lamp-2. Localization on the peptide backbones. AB - Lysosome membrane glycoproteins, lamp-1 and lamp-2, have been shown to contain 18 and 16 N-glycans, some of which are modified by poly-N-acetyl-lactosamine. We have localized the polylactosaminoglycans to specific sites on lamp-1 and lamp-2 purified from human chronic myelogenous leukemia cells. Polylactosaminoglycan containing glycopeptides, obtained by trypsin, pepsin, and V8 protease digestion of the glycoproteins, were isolated by Datura stramonium agglutinin affinity chromatography, gel filtration, and reverse phase high performance liquid chromatography. The poly-N-acetyllactosaminyl structures of isolated glycopeptides were confirmed by the susceptibility of their released oligosaccharides to endo-beta-galactosidase. Amino acid analysis and sequencing demonstrated that polylactosaminoglycans were located at Asn-34, Asn-93 and/or Asn-102, and Asn-195 and/or Asn-200 in lamp-1, and at Asn-4 and/or Asn-10, and Asn-279 in lamp-2. These results indicated that only certain glycosylation sites can be selectively modified by poly-N-acetyllactosamine, and those sites may confer the requirement by beta 1----3-N-acetylglucosaminyl transferase. PMID- 2243104 TI - The species-specific cell-binding site of the aggregation factor from the sponge Microciona prolifera is a highly repetitive novel glycan containing glucuronic acid, fucose, and mannose. AB - Species-specific adhesion of dissociated cells from the marine sponge Microciona prolifera is mediated by a Mr = 2 x 10(7) proteoglycan-like aggregation factor (MAF) via two highly polyvalent functional domains, a cell-binding and a self interaction domain. Glycopeptide N-glycosidase F release of a major glycan of Mr = 6.3 gamma 10(3) (G-6) from the MAF protein core resulted in the loss of cell binding activity, indicating a role of this polysaccharide molecule in MAF-cell association. The G-6 glycan was isolated and purified after complete Pronase digestion of MAF using gel electrophoresis, gel filtration, and ion exchange chromatography. Quantification of the amount of carbohydrate recovered in G-6 showed that one MAF molecule has about 950 repeats of this glycan. In its monomeric state G-6 did not display any measurable binding to cells (K alpha less than or equal to 10(3) M-1). Intermolecular cross-linking of the G-6 glycan with glutaraldehyde resulted, however, in the concomitant recovery of polyvalency (about 2200 repeats of G-6 per polymer of Mr greater than or equal to 1.5 x 10(7) and species-specific high cell binding affinity (K alpha = 1.6 x 10(9) M-1) but not of the MAF-MAF self-interaction activity. Thus, the G-6 glycan is the multiple low affinity cell-binding site involved in cell-cell recognition and adhesion of sponge cells. The G-6 glycan has 7 glucuronic acids, 3 fucoses, 2 mannoses, 5 galactoses, 14 N-acetylglucosamines, 2 sulfates, and 1 asparagine. Such a unique chemical composition indicates a new type of structure which includes features of glycosaminolycans and N-linked polysaccharides. PMID- 2243103 TI - Minimal sequence and factor requirements for the initiation of transcription from an atypical, TATATAA box-containing housekeeping promoter. AB - We have established the minimal sequence and factor requirements for both constitutive and viral-induced transcription from an atypical, TATATAA box containing human housekeeping promoter. Utilizing a transient cotransfection protocol, we have found that efficient transactivation of triosephosphate isomerase (TPI) gene transcription by the immediate early proteins of adenovirus and pseudorabies virus is dependent upon the same assembly of sequence elements that collectively confer minimal TPI promoter function in the absence of viral protein. These elements span TPI promoter positions -65 and -6 (where +1 is the transcription initiation site) and include not only a TFIID-responsive TATATAA box (-27 to -21) but a single GC box (-53 to -48) that binds Spl, and a novel cap proximal element (-18 to -6) that binds a 110-kDa nuclear factor that is present in HeLa cells. We demonstrate that these elements function in an interdependent fashion; deleting either GC box 1 or the cap proximal element completely or nearly abolished both basal transcription and viral transactivation. Therefore, these elements and their cognate factors represent the basal transcription initiation complex through which the immediate early protein of adenovirus or pseudorabies virus mediates the stimulation of TPI gene transcription. We discuss the implications of these data for both constitutive and viral-induced transcription. PMID- 2243105 TI - OXBOX, a positive transcriptional element of the heart-skeletal muscle ADP/ATP translocator gene. AB - Three positive transcriptional control regions have been identified in the promoter of the human heart-skeletal muscle adenine nucleotide translocator gene (ANT1). By transfecting promoter-chloramphenicol acetyltransferase fusion constructs into C2C12 myogenic cells, each positive region was found to increase transcription 2-3-fold. The first region spans from -123 to -674 base pairs (bp), the second from -2.6 to -3.1 kilobases, and the third from -3.1 to -8.8 kilobases. Linker-scanning mutants generated using the polymerase chain reaction and modified oligonucleotides have identified the OXBOX (5'-GGCTCTAAAGAGG) as the positive element within the -123 to -674-bp region. This element enhances transcription in muscle cells but not in HeLa cells, suggesting that it is muscle specific. Gel retardation experiments have revealed a factor from C2C12 cells which specifically binds to a 40-bp piece of the ANT1 promoter containing the OXBOX. Since the OXBOX is also found in the promoter of the human ATP synthase beta subunit gene, it is the first tissue-specific element identified which could coordinately regulate mitochondrial oxidative phosphorylation genes. PMID- 2243106 TI - Expression of wild-type and mutated forms of the catalytic (alpha) subunit of Caenorhabditis elegans casein kinase II in Escherichia coli. AB - A full-length Caenorhabditis elegans cDNA that encodes the alpha subunit of casein kinase II was inserted into the inducible bacterial expression vector pET3a to generate the plasmid pCK alpha. Escherichia coli DE21 lysozyme S that was transformed with pCK alpha expressed soluble, catalytically active casein kinase II alpha upon induction with isopropyl beta-D-thiogalactopyranoside. The expressed alpha subunit was purified to homogeneity with a 60% yield by chromatography on CM-Sephadex, P-11 phosphocellulose, and heparin-agarose. The Mr values estimated from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Mr = 42,000) or calculated from hydrodynamic measurements (s20,w = 3.3 S, Stokes radius = 2.8 nm, Mr = 37,000) were similar, thereby indicating that the expressed enzyme is monomeric. The native holoenzyme and the expressed alpha subunit exhibited several similar properties including the utilization of both ATP and GTP as substrates and the susceptibility to inhibition of phosphotransferase activity by low concentrations of heparin. However, the kcat for E. coli-derived alpha was only 9% of the kcat for the native holoenzyme, and catalytic activity was not stimulated by polyamines. Recombinant casein kinase II alpha aggregates at low ionic strength, and the aggregation is partially reversible. A mutant alpha subunit in which Lys74 and Lys75 were substituted by glutamic acid residues was constructed by site-directed mutagenesis. The mutant enzyme was not inhibited by typically effective concentrations of heparin (e.g. IC50 = 0.3 micrograms/ml) because the affinity of modified recombinant casein kinase II Glu-74Glu-75 for heparin decreased approximately 70-fold. Thus, Lys74 and Lys75 are implicated in the heparin binding, inhibitory domain. The successful expression of casein kinase II alpha in E. coli will facilitate the analysis of the structural basis for functional domains in this enzyme. PMID- 2243107 TI - Apolipoprotein B messenger RNA editing is developmentally regulated and widely expressed in human tissues. AB - Apolipoprotein B (apoB) messenger RNA (mRNA) undergoes posttranscriptional (C to U) editing, producing tissue-specific forms of apoB from the unedited (apoB100) and edited (apoB48) transcripts. ApoB mRNA editing is developmentally regulated in human fetal small intestine, producing parallel changes in the synthesis and secretion of apoB100 and apoB48. Neither fetal nor adult liver contained detectable levels (less than 1%) of edited apoB mRNA. By contrast, apoB mRNA is incrementally edited during development in several extraintestinal fetal tissues. These tissues demonstrated significant differences, however, in both the extent and developmental profile of apoB mRNA editing. Additionally, while apoB100 synthesis and secretion was demonstrated in these tissues, apoB48 synthesis was confined to the small intestine. Thus, although the molecular mechanism underlying this process remains unclear, the capacity to edit apoB mRNA is widely distributed among both fetal and adult tissues. We speculate that the asynchronous and developmentally modulated induction of apoB mRNA editing may provide a novel mechanism for regulating lipoprotein biogenesis in both the developing fetus and adult human. PMID- 2243109 TI - Identification of the keratan sulfate attachment sites on bovine fibromodulin. AB - The small keratan sulfate-substituted proteoglycan (fibromodulin) from articular cartilage was shown to contain keratan sulfate linked to the core protein through N-glycosidic linkages to residues Asn-109, Asn-147, Asn-182, and Asn-272. Biosynthetic experiments with articular chondrocytes in the presence of tunicamycin, an inhibitor of N-linked oligosaccharide synthesis, demonstrated a specific inhibition of [35S]SO4 incorporation into fibromodulin. Under the same conditions no effect on the addition of keratan sulfate to the large aggregating proteoglycan was detected. Fibromodulin substituted with keratan sulfate was purified from bovine articular cartilage extracts by density gradient centrifugation, ion-exchange chromatography, and gel-permeation chromatography. Isolation of glycosylated peptides from tryptic digests of fibromodulin by ion exchange chromatography and reversed-phase high performance liquid chromatography revealed four separate hexosamine-rich species, that were also immunoreactive with monoclonal antibody 5D4. Sequence analysis of these glycopeptides gave blank cycles at positions which corresponded to Asn followed by X-Ser/Thr in the sequence derived from cDNA (Oldberg, A., Antonsson, P., Lindblom, K., and Heinegard, D. (1989) EMBO J. 8, 2601-2604). Hence, all four Asn residues in the leucine-rich region of the fibromodulin core protein can serve as acceptor sites for keratan sulfate addition. PMID- 2243108 TI - Association of cell surface heparan sulfate proteoglycans of Schwann cells with extracellular matrix proteins. AB - The terminal differentiation of Schwann cells is dependent on contact with basement membrane. The present study was undertaken to investigate the role of cell surface heparan sulfate proteoglycans (HSPGs) in mediating Schwann cell responses to extracellular matrix contact. Phosphatidylinositol-specific phospholipase C-releasable cell surface HSPGs purified from cultures of neonatal rat Schwann cells were subjected to affinity chromatography on immobilized laminin and fibronectin. Binding of the HSPG to both affinity matrices was observed. The strength of the association, however, was sensitive to the ionic strength of the buffer. In 0.1 M Tris-HCl, HSPG binding was essentially irreversible whereas in physiological ionic strength buffer (e.g. 0.142 M NaCl, 10 mM Tris), weaker binding was detected as a delay in elution of the HSPG from the affinity columns. Further studies of HSPG-laminin binding suggested that the binding was mediated by the glycosaminoglycan chains of the proteoglycans. Results of equilibrium gel filtration chromatography provided additional evidence for a reversible association of the HSPG and laminin with a Kd of approximately 1 x 10(-6) M. When Schwann cells were plated on plastic dishes coated with laminin, the cells attached and extended long slender processes. Inclusion of heparin, but not chondroitin sulfate, in the assay medium resulted in partial inhibition of process extension, but at concentrations of heparin which were higher than that needed to disrupt laminin-HSPG association in vitro. Addition of anti-integrin receptor antibodies resulted in more extensive inhibition of laminin-dependent process extension. Anti-integrin antibodies plus heparin essentially totally inhibited laminin-dependent process extension. These results demonstrate that cell surface HSPGs are capable of reversible association with extracellular matrix molecules and suggest that HSPG-laminin interactions play a role in laminin-dependent Schwann cell spreading. PMID- 2243110 TI - A new Acanthamoeba myosin heavy chain. Cloning of the gene and immunological identification of the polypeptide. AB - An Acanthamoeba myosin heavy chain has been identified whose tail domain amino acid sequence distinguishes it from Acanthamoeba myosins IB, IC, and II. The gene for this novel myosin heavy chain spans approximately 6.8 kilobases, is split by 17 introns, and encodes a 177-kDa polypeptide. While the amino-terminal approximately 90 kDa of this polypeptide is highly similar to the globular head sequences of myosins I and II, its approximately 87-kDa tail domain shows essentially no similarity to the tail sequences of either type of myosin. The only exception to this is the carboxyl-terminal approximately 50-amino acid region of the polypeptide, which is homologous to the carboxyl termini of the myosins I. Interestingly, this approximately 50-residue segment has been shown to exist in a diverse family of cytoskeleton-associated proteins that include nonreceptor tyrosine kinases, phospholipase C gamma, and fodrin (Rodaway, A. R. F., Sternberg, M. J. E., and Bentley, D. L. (1989) Nature 342, 624). Sequence analysis indicates that the tail domain of this new myosin is incapable of forming a myosin II-like coiled-coil structure, implying that the protein is single-headed and nonfilamentous. For this reason we have tentatively classified it as a high molecular weight form of myosin I (HMWMI). To determine if HMWMI exists in cells, antiserum was raised against a bacterially expressed fusion peptide made using a cDNA clone encoding most of the unique HMWMI tail domain. This antiserum does not recognize Acanthamoeba myosins IB, IC, or II but does recognize a single polypeptide in whole cell extracts with the mobility predicted for the HMWMI heavy chain. This protein is precipitated from crude extracts using F-actin and released from the pellet by ATP, supporting its classification as a member of the myosin family of proteins. PMID- 2243111 TI - A novel adenylylation process in liver plasma membrane-bound proteins. AB - Rat liver plasma membrane contains five distinct polypeptides of apparent molecular mass of 130, 120, 110, 100, and 86 kDa which are labeled upon incubation with [alpha-32P]ATP as well as with [gamma-32P]ATP. Covalently bound adenosine 5'-monophosphate to some of the polypeptides was identified using nonhydrolyzable analogues of ATP. Chase experiments of alpha-32P-nucleotide labeled polypeptides with different nonradiolabeled phosphocompounds and sensitivity to different inhibitors demonstrate that the 86-kDa polypeptide is a phosphoesterase, forming a catalytic intermediate. On the other hand, the comparative slow rate of turnover of the polypeptides of higher molecular mass (130, 120, 110, and 100 kDa) suggests that the bound AMP could play a regulatory rather than a catalytic role. Using the nonhydrolyzable ATP analogue [alpha, beta methylene]ATP and dilution experiments with Triton X-100-solubilized membranes, it has been possible to identify the 130-kDa adenylylated polypeptide as a possible target of an adenylylating system. These polypeptides, except the 86-kDa phosphoesterase, are affected in their electrophoretic mobility in the absence of beta-mercaptoethanol. An intercatenary disulfide bond(s) appear(s) to link the polypeptide(s) of 120 kDa and/or 110 kDa in a dimeric structure of apparent molecular mass of 240 kDa. All five polypeptides labeled with [alpha-32P]ATP are glycoproteins bound to the cell plasma membrane. PMID- 2243112 TI - Isolation of four core histones from human sperm chromatin representing a minor subset of somatic histones. AB - Using high performance liquid chromatography we have successfully purified four core histones from mature human sperm chromatin. The H2A variants present in sperm (H2A.X and limited H2A.Z) have been shown previously to be minor variants in somatic chromatin. The histones are highly modified as evidenced by extensive acetylation and an as yet uncharacterized multicharge modification of H2B. Based on our data, we conclude that histone proteins are a minor component of each mature spermatozoa. Given the unique nature of the histone variants present in sperm, we propose that this chromatin component has a specific function and may possibly facilitate the programming of genes which will be active in early development. PMID- 2243113 TI - Zinc-induced secondary structure transitions in human sperm protamines. AB - Using CD we show that human group II protamines undergo novel zinc-dependent secondary structure transitions. The CD spectra of protamine is characteristic of random coil proteins with a large minima at 197 nm. Upon the addition of 1 mM zinc, the magnitude of this minima is decreased by 44%. This spectral change is not induced by 1 mM calcium or magnesium. Cadmium, which has chemical properties similar to zinc, can also induce the structural transition although not as effectively as zinc. The spectral changes that accompany zinc binding are indicative of an increase in beta-turn and anti-parallel beta-sheet structures. This is consistent with the predicted secondary structure for protamines which is dominated by beta-turns. Our data support a model in which protamine adopts a folded structure in the presence of zinc. We propose that a zinc-modulated structure is physiologically significant considering the relatively high levels of zinc in human sperm. PMID- 2243115 TI - Several regions of human estrogen receptor are involved in the formation of receptor-heat shock protein 90 complexes. AB - Several mutants of the human estrogen receptor (ER) were transiently expressed in Cos 7 cells in order to determine the regions involved in the formation of complexes with the heat shock protein Mr approximately 90,000 (hsp 90). The formation of the cytosol non-DNA binding 8-9 S complexes (8-9 S ER) was monitored by glycerol gradient ultracentrifugation. It was established that the N-terminal region of the receptor, including the two zinc fingers of the DNA binding domain (DBD), is not required for the formation of the 8-9 S ER complexes. Conversely, deletion of the entire ligand binding domain (LBD) produced truncated receptor mutants that are constitutive transcriptional activators and did not form 8-9 S ER complexes, confirming results obtained previously with the glucocorticosteroid receptor (Pratt, W.B., Jolly, D.J., Pratt, D.V., Hollenberg, S.M., Giguerre, V., Cadepond, F., Schweizer-Groyer, G., Catelli, M.G., Evans, R.M., and Baulieu, E.E. (1988) J. Biol. Chem. 263, 267-273). However, no limited subregion of the LBD was found to be uniquely involved in hsp 90 binding. A highly positively charged region situated at the C-terminal extremity of the DBD (between amino acids 251 and 271) also appeared to be implicated. Although not sufficient, this sequence is necessary for the formation of the 8-9 S ER; it also corresponds to the NL1 nuclear localization domain of steroid receptors. Taken together, these results suggest that the formation of complexes with hsp 90 involves several receptor regions, and they are consistent with the proposal that hsp 90 inhibits receptor function and can be released by hormone binding to the LBD. PMID- 2243114 TI - Cellular processing of the interleukin-2 fusion toxin DAB486-IL-2 and efficient delivery of diphtheria fragment A to the cytosol of target cells requires Arg194. AB - We have used site-directed mutagenesis to examine the role played by Arg191, Arg193, and Arg194 of the fusion toxin DAB486-IL-2 in the intoxication of high affinity interleukin-2 receptor-bearing T-lymphocytes. These arginine residues are positioned in the proteolytically sensitive 14-amino acid loop subtended by the disulfide bond between Cys187 and Cys202 in this fusion toxin. DAB486-IL-2 was formed by the genetic substitution of the native diphtheria toxin receptor binding domain with human interleukin-2 (Williams, D.P., Parker, K., Bacha, P., Bishai, W., Borowski, M., Genbauffe, F., Strom, T.B., and Murphy, J.R. (1987) Protein Eng. 1, 493-498). We demonstrate that substitution of Arg194 with Gly results in a 1000-fold loss of DAB486-IL-2 potency. Since trypsin "nicking" of the Gly194 mutant restores biologic activity, we conclude that Arg194 is required for the cellular processing of the fusion toxin which results in the release of fragment A into the cytosol. PMID- 2243116 TI - Arginine 127 stabilizes the transition state in carboxypeptidase. AB - Crystallographic studies suggest that Arg-127 is a key amino acid in the hydrolysis of peptides and esters by carboxypeptidase A. The guanidinium group of Arg-127 is hypothesized to stabilize the oxyanion of the tetrahedral intermediate formed by the attack of water on the scissile carbonyl bond. We have replaced this amino acid in rat carboxypeptidase A1 with lysine (R127K), methionine (R127M), and alanine (R127A), in order to define the role of Arg-127 in carboxypeptidase catalyzed hydrolysis. The wild-type and mutant enzymes were expressed in yeast and purified. Kinetic studies show that Arg-127 substitution decreases kcat for both ester and amide substrates, whereas Km is relatively unchanged; for R127M and R127A this corresponds to a 6 kcal/mol decrease in transition state stabilization of the rate-limiting step. The binding affinity for the phosphonate transition state analog, Cbz-Phe-Ala(P)-OAla, was decreased by 5.4 kcal/mol, whereas binding affinity for the ground state inhibitor, DL benzylsuccinic acid, was decreased by only 1.7 kcal/mol for R127M. Electrostatic calculations employing a finite difference solution to the Poisson-Boltzmann equation predict that the positive charge of Arg-127 should stabilize the transition state by 6-8 kcal/mol. Therefore, the experimental and theoretical data suggest that the primary role of Arg-127 is stabilization of the transition state through electrostatic interaction with the oxyanion. PMID- 2243117 TI - Computer-assisted liquid chromatography for automated qualitative and quantitative analysis of toxic drugs. AB - A computer-assisted liquid chromatographic system (MCASYST) is evaluated for automatic qualitative and quantitative analysis of toxic drugs in poisoned human fluids. The system performance is confirmed by the actual analyses of several cases of poisoning. The results indicate that the accuracy of identification by retention prediction and UV spectral search is very high, and quantitation by the memorized calibration curves can be performed very conveniently. However, it is difficult at present to identify all peaks that appear in chromatograms for human urine and serum because the drugs may be changed to their metabolites in those fluids. Metabolite identification will be the next step to improve the performance of this system. PMID- 2243118 TI - Antibiotic proteins of human neutrophils. PMID- 2243119 TI - Expression of human bone-related proteins in the hematopoietic microenvironment. AB - Given the intimate relationship between bone and bone marrow, we hypothesized that the human bone marrow may function as a source (or reservoir) of bone forming progenitor cells. We observed a population of cells within the bone marrow which produce bone-specific or bone-related proteins. The production of these proteins was developmentally regulated in human long-term bone marrow cell cultures; the bone protein-producing cells (BPPC) are observed under serum-free, short-term culture conditions, respond to bone-related and not hematopoietic growth factors, and are derived from a population of low-density, nonadherent, My10-negative (or low My10 density), marrow cells (My10 is an antigen found on most hematopoietic progenitor cells). Cultivation of marrow-derived BPPC in secondary, serum-containing cultures results in their differentiation into osteoblastlike cells. At this stage of development, BPPC produce an extracellular matrix which incorporates both bone-related proteins and radiolabeled calcium. Human bone marrow BPPC thus represent a newly described cell phenotype important to both bone and hematopoietic cell biology. PMID- 2243120 TI - Whole-body lipolysis and triglyceride-fatty acid cycling in cachectic patients with esophageal cancer. AB - Whole-body lipolytic rates and the rate of triglyceride-fatty acid cycling (reesterification of fatty acids released during lipolysis) were measured with stable isotopic tracers in the basal state and during beta-adrenergic blockade with propranolol infusion in five cachectic patients with squamous cell carcinoma of the esophagus, five cachectic cancer-free, nutritionally-matched control patients, and 10 healthy volunteers. Resting energy expenditure and plasma catecholamines were normal in all three groups. The basal rate of glycerol appearance in blood in the patients with cancer (2.96 +/- 0.45 mumol.kg-1.min-1) was similar to that in the nutritionally matched controls (3.07 +/- 0.28 mumol.kg 1.min-1), but 48% greater than in the normal-weight volunteers (2.00 +/- 0.16 mumol.kg-1.min-1) (P = 0.028). The antilipolytic effect of propranolol and the rate of triglyceride-fatty acid cycling in the patients with cancer were also similar in the cachectic control group and approximately 50% greater than in the normal-weight volunteers, but the differences were not statistically significant because of the variability in the data. We conclude that the increase in lipolysis and triglyceride-fatty acid cycling in "unstressed" cachectic patients with esophageal cancer is due to alterations in their nutritional status rather than the presence of tumor itself. Increased beta-adrenergic activity may be an important contributor to the stimulation of lipolysis. PMID- 2243121 TI - Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda. AB - Uroporphyrinogen decarboxylase (URO-D) is a cytosolic heme-biosynthetic enzyme that converts uroporphyrinogen to coproporphyrinogen. Defects at the uroporphyrinogen decarboxylase locus cause the human genetic disease familial porphyria cutanea tarda. A splice site mutation has been found in a pedigree with familial porphyria cutanea tarda that causes exon 6 to be deleted from the mRNA. The intron/exon junctions on either side of exon 6 fall between codons, so the resulting protein is shorter than the normal protein, missing only the amino acids coded by exon 6. The shortened protein lacks catalytic activity, is rapidly degraded when exposed to human lymphocyte lysates, and is not detectable by Western blot analysis in lymphocyte lysates derived from affected individuals. The mutation was detected in five of 22 unrelated familial porphyria cutanea tarda pedigrees tested, so it appears to be common. This is the first splice site mutation to be found at the URO-D locus, and the first mutation that causes familial porphyria cutanea tarda to be found in more than one pedigree. PMID- 2243122 TI - Skeletal muscle metabolism is a major determinant of resting energy expenditure. AB - Energy expenditure varies among people, independent of body size and composition, and persons with a "low" metabolic rate seem to be at higher risk of gaining weight. To assess the importance of skeletal muscle metabolism as a determinant of metabolic rate, 24-h energy expenditure, basal metabolic rate (BMR), and sleeping metabolic rate (SMR) were measured by indirect calorimetry in 14 subjects (7 males, 7 females; 30 +/- 6 yr [mean +/- SD]; 79.1 +/- 17.3 kg; 22 +/- 7% body fat), and compared to forearm oxygen uptake. Values of energy expenditure were adjusted for individual differences in fat-free mass, fat mass, age, and sex. Adjusted BMR and SMR, expressed as deviations from predicted values, correlated with forearm resting oxygen uptake (ml O2/liter forearm) (r = 0.72, P less than 0.005 and r = 0.53, P = 0.05, respectively). These findings suggest that differences in resting muscle metabolism account for part of the variance in metabolic rate among individuals and may play a role in the pathogenesis of obesity. PMID- 2243123 TI - Immunogenicity in animals of a polysaccharide-protein conjugate vaccine against type III group B Streptococcus. AB - The native capsular polysaccharide of type III group B Streptococcus elicits a specific antibody response in only 60% of nonimmune human subjects. To enhance the immunogenicity of this polysaccharide, we coupled the type III polysaccharide to tetanus toxoid. Prior to coupling, aldehyde groups were introduced on the polysaccharide by controlled periodate oxidation, resulting in the conversion of 25% of the sialic acid residues of the polysaccharide to residues of the 8-carbon analogue of sialic acid, 5-acetamido-3,5-dideoxy-D-galactosyloctulosonic acid. Tetanus toxoid was conjugated to the polysaccharide by reductive amination, via the free aldehyde groups present on the partially oxidized sialic acid residues. Rabbits vaccinated with the conjugate vaccine produced IgG antibodies that reacted with the native type III group B streptococcal polysaccharide (3/3 rabbits), while rabbits immunized with the unconjugated type III polysaccharide failed to respond (0/3 rabbits). Sera from animals receiving conjugate vaccine opsonized type III group B streptococci for phagocytic killing by human peripheral blood leukocytes, and protected mice against lethal challenge with live type III group B streptococci. The results suggest that this method of conjugation to a carrier protein may be a useful strategy to improve the immunogenicity of the type III group B Streptococcus polysaccharide in human subjects. PMID- 2243124 TI - Transforming growth factor-beta activity in sheep lung lymph during the development of pulmonary hypertension. AB - Chronic pulmonary hypertension is associated with extensive structural remodeling of the pulmonary arterial bed. The structural changes in the arterial walls include increased production of extracellular matrix components and smooth muscle cell hypertrophy, changes that have been similarly induced by transforming growth factor-beta (TGF-beta) in culture. In the present study, experiments were performed to determine whether TGF-beta is present in sheep lung lymph, and whether TGF-beta levels were altered in an animal model of chronic pulmonary hypertension induced by continuous air embolization. Several standard biological assays for TGF-beta activity were used for these determinations including soft agar assays, inhibition of epithelial cell proliferation, and a TGF-beta-specific radioreceptor assay. In each case, control lung lymph contained high concentrations of TGF-beta (100 ng/ml) which required transient acidification for detection. Samples of lung lymph from hypertensive sheep showed a transient and early two- to threefold increase in concentrations of latent TGF-beta. This activity could be partially blocked by TGF-beta antibodies. These studies indicate that sheep lung lymph contains TGF-beta and that the level of TGF-beta increases early during the development of pulmonary hypertension. Thus, TGF-beta may contribute to the development of the structural changes in the pulmonary arteries that occur during the onset of chronic pulmonary hypertension. PMID- 2243125 TI - A mutation in the gene for type III procollagen (COL3A1) in a family with aortic aneurysms. AB - Experiments were carried out to test the hypothesis that familial aortic aneurysms, either thoracic or abdominal, are caused by mutations in the gene for type III procollagen (COL3A1) similar to mutations in the same gene that have been shown to cause rupture of aorta and other disastrous consequences in the rare genetic disorder known as Ehlers-Danlos syndrome type IV. A family was identified through a 37-yr-old female captain in the United States Air Force who was scrutinized only because many of her direct blood relatives had died of ruptured aortic aneurysms. The woman was heterozygous for a single-base mutation that converted the codon for glycine 619 of the alpha 1(III) chain of type III procollagen to a codon for arginine. Studies on cultured skin fibroblasts demonstrated the mutation caused synthesis of type III procollagen that had a decreased temperature for thermal unfolding of the protein. The same mutation was identified in DNA extracted from pathologic specimens from her mother who had died at the age of 34 and a maternal aunt who died at the age of 55 of aortic aneurysms. Examination of DNA from samples of saliva revealed that the woman's daughter, her son, a brother, and an aunt also had the mutation. The results demonstrated that mutations in the type III procollagen gene can cause familial aortic aneurysms and that DNA tests for such mutations can identify individuals at risk for aneurysms. PMID- 2243126 TI - Mechanism of acid-induced release of secretin in rats. Presence of a secretin releasing peptide. AB - In fasting rats, intraduodenal infusion of dilute hydrochloric acid results in significant increases in both pancreatic exocrine secretion and plasma concentration of secretin. To test the hypothesis that acid-induced release of secretin is mediated by a secretin-releasing factor (S-RF), anesthetized rats were prepared with pyloric ligation, duodenal and jejunal cannulas, and pancreatic duct cannulas. Donor rats were infused intraduodenally with 0.01 N HCl, 0.15 M NaCl, or a combination of 0.01 N HCl and 0.05 N NaHCO3 at 0.3 ml/min for 1.5 h, and the perfusates were collected via jejunal cannulas. The perfusates with pH adjusted to 6.0 were concentrated threefold and infused into the duodena of recipient rats. The concentrate of acid perfusate (CAP) significantly increased both pancreatic volume flow and bicarbonate output and plasma concentration of secretin, whereas concentrates of the saline perfusate (CSP) or the perfusate of a combination of 0.01 N HCl and 0.05 N NaHCO3 (CABP) did not influence pancreatic secretion or plasma concentration of secretin. The increased pancreatic secretion by CAP was attributed to increased circulating secretin because when secretin was immunoneutralized by a rabbit antisecretin serum, CAP stimulated pancreatic secretion was abolished. The bioactivity of CAP was trypsin sensitive and heat stable. The active substance in CAP had a molecular weight of less than 5,000 and greater than 1,000, as determined by ultrafiltration and bioassay. In conclusion, dilute HCl releases an S-RF into the upper small intestinal lumen to stimulate release of secretin. This substance, with molecular weight of less than 5,000, is heat stable and trypsin sensitive. Thus, the acid stimulated release of secretin is mediated by a secretin-releasing peptide in the upper small intestinal lumen. PMID- 2243127 TI - Elevated insulin receptor content in human breast cancer. AB - The growth of breast cancer cells is under the regulation of hormones, growth factors, and their receptors. In the present study, we have employed a new, sensitive, and specific radioimmunoassay for the direct measurement of insulin receptors in surgical specimens of breast cancers. In 159 specimens the insulin receptor content was 6.15 +/- 3.69 ng/0.1 mg protein. This value was more than sixfold higher than the mean value found in both 27 normal breast tissues obtained at total mastectomy (0.95 + 0.68, P less than 0.001) and in six normal specimens obtained from reduction mammoplasty (0.84 +/- 0.78, P less than 0.001). The insulin receptor content in breast cancer tissues was also higher than in any normal tissue investigated including liver (Pezzino, V., V. Papa, V. Trischitta, A. Brunetti, P.A. Goodman, M.K. Treutelaar, J.A. Williams, B.A. Maddux, R. Vigneri, and I.D. Goldfine, 1989. Am. J. Physiol. 257:E451-457). The insulin receptor in breast cancer retained its ability to both bind insulin and undergo insulin-induced tyrosine kinase activation. Immunostaining of the specimens revealed that the insulin receptor was present in malignant epithelial cells, but was not detected in stromal and inflammatory cells. Univariant analysis revealed that the insulin receptor content of the tumors correlated positively with tumor size (P = 0.014), histological grading (P = 0.030), and the estrogen receptor content (P = 0.035). There were no significant correlations between insulin receptor content and the age, body weight, menopausal status, and nodal involvement of the patients. These studies indicate, therefore, that the insulin receptor content is increased in breast cancers and raise the possibility that the insulin receptor may have a role in the biology of these tumors. PMID- 2243128 TI - Two different point G to A mutations in exon 10 of the porphobilinogen deaminase gene are responsible for acute intermittent porphyria. AB - Two mutations of the porphobilinogen (PBG) deaminase gene resulting in cross reacting immunological material (CRIM) positive forms of acute intermittent porphyria (AIP) have been identified by in vitro amplification of cDNA and cloning of the amplified products in a bacterial expression vector. Both mutations resulted from G to A transitions in exon 10 of the gene and produced arginine to glutamine substitutions in the abnormal protein. Expression of mutant cDNA in Escherichia coli reveals that one but not the other of these amino acid changes results in a striking decrease of the optimal pH of the mutated enzyme. One or the other of these two mutations accounted for the defect causing AIP in six unrelated patients among the eight patients evaluated with the CRIM positive subtype of this disorder. PMID- 2243129 TI - Angiotensin and thromboxane in the enhanced renal adrenergic nerve sensitivity of acute renal failure. AB - The roles of intrarenal angiotensin (A) and thromboxane (TX) in the vascular hypersensitivity to renal nerve stimulation (RNS) and paradoxical vasoconstriction to renal perfusion pressure (RPP) reduction in the autoregulatory range in 1 wk norepinephrine (NE)-induced acute renal failure (ARF) in rats were investigated. Renal blood flow (RBF) responses were determined before and during intrarenal infusion of an AII and TXA2 antagonist. Saralasin or SQ29548 alone partially corrected the slopes of RBF to RNS and RPP reduction in NE-ARF rats (P less than 0.02). Saralasin + SQ29548 normalized the RBF response to RNS. While combined saralasin + SQ29548 eliminated the vasoconstriction to RPP reduction, similar to the effect of renal denervation, appropriate vasodilatation was not restored. Renal vein norepinephrine efflux during RNS was disproportionately increased in NE-ARF (P less than 0.001) and was suppressed by saralasin + SQ29548 infusion (P less than 0.005). It is concluded that the enhanced sensitivity to RNS and paradoxical vasoconstriction to RPP reduction in 1 wk NE-ARF kidneys are the result of intrarenal TX and AII acceleration of neurotransmitter release to adrenergic nerve activity. PMID- 2243130 TI - Physiological measurements of luminal stirring in the dog and human small bowel. AB - The resistance to absorption resulting from poor stirring of luminal contents (RLum) is considered to be equivalent to an unstirred layer of greater than 600 microns in the human small intestine. We measured RLum in the jejunum of conscious dogs by assessing the absorption rate of two rapidly absorbed probes, glucose, and [14C]warfarin. When RLum was expressed as an unstirred layer, the maximal thickness of the unstirred layer (assuming negligible epithelial cell resistance) was only approximately 35 and 50 microns for perfusion rates of 26 and 5 ml/min, respectively. Maximal unstirred layer thickness for the human jejunum, calculated from previous studies of glucose absorption, yielded a mean value of only 40 microns (range: 23 to 65 microns). Since epithelial resistance appears to be negligible during absorption of low concentrations of glucose, the maximal unstirred layer of 40 microns should be close to the true value for glucose in the human small intestine. We conclude that the unstirred layer for rapidly absorbed compounds in dogs and man are less than one-tenth of previously reported values, but this layer still may remain the rate limiting step in absorption of rapidly transported compounds. PMID- 2243131 TI - Inactivation of beef brain alpha-ketoglutarate dehydrogenase complex by valproic acid and valproic acid metabolites. Possible mechanism of anticonvulsant and toxic actions. AB - The anticonvulsant valproic acid (VPA, 2-n-propylpentanoic acid) causes inhibition of the citric acid cycle and elevations of central nervous system (CNS) gamma-aminobutyric acid (GABA) levels, which correlates with anticonvulsant action. No unifying mechanism for these actions of VPA has won general acceptance. alpha-Ketoglutarate dehydrogenase complex (KDHC) is a critical control enzyme in the CNS. We hypothesized that VPA may be an inhibitor of this enzyme since decreased KDHC activity would reduce substrate flux through the citric acid cycle and may increase flux into GABA synthesis. To test this hypothesis, inhibition of purified beef brain KDHC by VPA and its metabolites 2-n propylpent-2-enoic acid (delta 2,3 VPE) and their coenzyme A (CoA) derivatives were studied. Preincubation of the NADH-reduced enzyme with delta 2,3 VPE, VPA CoA, and delta 2,3 VPE-CoA caused time-dependent inactivation, reversible by addition of CoA. Under steady-state conditions, delta 2,3 VPE and VPA-CoA were competitive inhibitors of KDHC and delta 2,3 VPE-CoA was a mixed inhibitor. These observations have implications for the molecular mechanisms of VPA action. VPA derivatives cause inactivation and inhibition of KDHC, which may explain the anticonvulsant and some toxic actions of VPA. PMID- 2243132 TI - Pathogenesis of hyperadrenergic orthostatic hypotension. Evidence of disordered venous innervation exclusively in the lower limbs. AB - The pathogenesis of hyperadrenergic orthostatic hypotension was studied in eight patients. Correction of the abnormal orthostatic changes by an inflated pressure suit (MAST) confirmed previous evidence of excessive gravitational pooling of blood in the leg veins. Intravenous L-norepinephrine infusion raised diastolic blood pressure in the same relationship to the infusion-induced increments in plasma norepinephrine concentrations as in normal subjects, indicating normal arteriolar responses. Contractile responses of the veins to infused L norepinephrine were measured with a linear variable differential transformer (LVDT). The venous responses of hand veins in the patients fell within the 95% confidence limits of the responses of normal hand veins, as did the responses of foot veins in the seven normal subjects. However, foot veins of the patients with hyperadrenergic orthostatic hypotension, and both hand and foot veins of patients with "diffuse" autonomic failure, were supersensitive to norepinephrine, as reflected by a steeper slope of the regression of log (norepinephrine infusion rate) on percentage reduction in venous distensibility, and a significantly lower ED50 (i.e., norepinephrine infusion rate that induced 50% reduction in venous distensibility). The findings suggest anatomical or functional postganglionic denervation of lower limb veins causing excessive gravitational blood pooling with consequent orthostatic hypotension in these patients. PMID- 2243133 TI - Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. AB - Pearson's marrow-pancreas syndrome (McKusick No. 26056) is a fatal disorder of hitherto unknown etiology involving the hematopoietic system, exocrine pancreas, liver, and kidneys. The observation of high lactate/pyruvate molar ratios in plasma and abnormal oxidative phosphorylation in lymphocytes led us to postulate that Pearson's syndrome belongs to the group of mitochondrial cytopathies. Since rearrangements of the mitochondrial genome between direct DNA repeats were consistently found in all tissues tested, our results show that this disease is in fact a multisystem mitochondrial disorder, as suggested by the clinical course of the patients. Based on these observations, we would suggest giving consideration to the hypothesis of a defect of oxidative phosphorylation in elucidating the origin of other syndromes, especially those associated with an abnormal oxidoreduction status in plasma. PMID- 2243134 TI - Reduced beta-cell glucose transporter in new onset diabetic BB rats. AB - Previous studies from our laboratories have suggested a defect in glucose transport in islets isolated from BB rats on the first day of overt diabetes. To quantitate by immunostaining the glucose transporter of beta-cells (GLUT-2) before and at the onset of autoimmune diabetes we employed an antibody to its COOH-terminal octapeptide. On the first day of overt diabetes, defined as the day the daily blood glucose first reached 200 mg/dl, the volume density ratio of GLUT 2-positive to insulin-positive beta-cells was only 0.48 +/- 0.06, compared to 0.91 +/- 0.02 in age-matched nondiabetic diabetes-resistant controls (P less than 0.001). In age-matched nondiabetic diabetes-prone rats, most of which would have become diabetic, the ratio was 0.85 +/- 0.02, also less than the controls (P less than 0.05). Protein A-gold labeling of GLUT-2 in beta-cells of day 1 diabetic rats revealed 2.17 +/- 0.16 gold particles per micrometer length of microvillar plasma membranes compared to 3.91 +/- 0.14 in controls (P less than 0.001) and 2.87 +/- 0.24 in the nondiabetic diabetes-prone rats (P less than 0.02). Reduction in GLUT-2 correlates temporally with and may contribute to the loss of glucose-stimulated insulin secretion that precedes profound beta-cell depletion of autoimmune diabetes. PMID- 2243135 TI - A novel X-linked combined immunodeficiency disease. AB - A novel X-linked combined immunodeficiency disease was found in five living males in an extended family in the United States. The age of the affected males ranged from 2.5 to 34 yr. The most prominent clinical abnormalities were a paucity of lymphoid tissue; recurrent sinusitis, otitis media, bronchitis, and pneumonia; severe varicella; and chronic papillomavirus infections. The principal immunologic features of the disorder were normal concentrations of serum immunoglobulins but restricted formation of IgG antibodies to immunogens; normal numbers of B cells and NK cells but decreased numbers of CD4+ and CD8+ T lymphocytes, particularly the CD45RA+ subpopulations; diminished proliferative responses of blood T cells to allogeneic cells, mitogens and antigens; and decreased production of IL-2 by mitogen stimulated blood lymphocytes. Thus, affected males in this family carry an abnormal gene on their X chromosome that results in a combined immunodeficiency that is distinct from previously reported disorders. PMID- 2243136 TI - Epidermal growth factor regulates the in vitro sensitivity of human ovarian carcinoma cells to cisplatin. AB - Cisplatin (DDP) is the most effective drug for the treatment of human ovarian cancer, but the mechanisms that determine sensitivity to the cytotoxic action of DDP are not well understood. Treatment of two human ovarian carcinoma cell lines with epidermal growth factor (EGF) simultaneously increased sensitivity to DDP and caused a persistent change in morphology in the absence of any mitogenic effect. Sensitization to DDP was shown to be dependent on both EGF concentration and EGF receptor number in C127 mouse fibroblasts expressing the human EGF receptor after transfection with a pBPV plasmid construct containing the human EGF receptor gene under control of the transferrin receptor 3'-inducible regulator. Sensitization of human ovarian carcinoma cells to DDP was not blocked by inhibition of protein synthesis. EGF did not enhance sensitivity to DDP or alter morphology in DDP-resistant human ovarian carcinoma cells despite the presence of functional EGF receptors on these cells. These results showed that elements of the signal transduction pathway activated by EGF determined cellular sensitivity to DDP, and that a DDP-resistant phenotype is associated with a defect in this signal transduction pathway. PMID- 2243137 TI - Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo. AB - Whether parenchymal or nonparenchymal liver cells play a predominant role in the pathophysiology of hepatic fibrosis has not been firmly established in vivo. We have addressed this question by quantitating the relative abundance of specific mRNAs for collagen types I, III, and IV, and laminin in purified populations of hepatocytes, sinusoidal endothelial cells, and lipocytes from normal and fibrotic rat liver. In normal liver, type I collagen gene expression was minimal in all cell types; mRNA for types III and IV collagen were apparent in endothelial cells and lipocytes, but not in hepatocytes. Laminin mRNA was present in all cell types. Induction of fibrogenesis by either bile duct ligation or carbon tetrachloride administration was associated with a substantial increase in mRNA for types I and III collagen in nonparenchymal cells. Lipocytes from fibrotic animals exhibited a greater than 30-fold increase in type I collagen mRNA relative to normal lipocytes, and greater than 40-fold relative to hepatocytes. Type III collagen mRNA reached 5 times that in normal lipocytes and greater than 120 times that in hepatocytes. Endothelial cells exhibited an isolated increase in type I collagen mRNA, reaching five times that in normal liver. Type IV collagen and laminin gene expression were not significantly increased in nonparenchymal cells during fibrogenesis; in fact, mRNA for type IV collagen and laminin decreased by up to 50% in endothelial cells. Despite the pronounced changes that occurred in matrix gene expression in nonparenchymal cells during fibrogenesis, no change was noted in hepatocytes. We conclude that nonparenchymal liver cells, particularly lipocytes, are important effectors of hepatic fibrosis in vivo. PMID- 2243138 TI - A phosphatase activity present in peripheral blood myeloid cells of chronic myelogenous leukemia patients but not normal individuals alters nuclear protein binding to transcriptional enhancers of interferon-inducible genes. AB - Cytoplasmic protein from peripheral blood myeloid cells of chronic myelogenous leukemia (CML) patients altered the electrophoretic mobility of complexes formed between nuclear proteins and interferon-inducible transcriptional enhancers. Immature myeloid marrow cells (blasts and promyelocytes) have a higher level of this activity than do mature myeloid marrow cells (bands and polys). This activity, which is not detectable in the peripheral blood cells of normal individuals, is at least 50-fold higher in CML marrow blasts and promyelocytes than that found in marrow blasts and promyelocytes of normal individuals. This activity was inhibited by in vivo incubation of immature myeloid cells with the phosphatase inhibitor, sodium orthovanadate (0.2 mM), and by adding orthovanadate (20 mM) directly to cytoplasmic proteins of myeloid cells. Interferon-alpha (1,000 U/ml) reduced the effects of the CML myeloid cell cytoplasmic protein on the electrophoretic mobility of nuclear protein-DNA complexes. These data suggest that a unique phosphatase may be involved in the abnormalities in CML which are modulated by interferon-alpha. PMID- 2243139 TI - CD4-Pseudomonas exotoxin conjugates delay but do not fully inhibit human immunodeficiency virus replication in lymphocytes in vitro. AB - The CD4 molecule is a high affinity receptor for the human immunodeficiency virus (HIV) envelope glycoprotein (gp160 or gp120). This glycoprotein is expressed on the surface membrane of cells infected with HIV. It has, therefore, been suggested that a soluble form of CD4 might be used as a targeting agent to deliver toxins selectively to cells infected with HIV. We demonstrate that CD4 Pseudomonas exotoxin A (PE) conjugates inhibit the proliferation of gp160 transfected Chinese hamster ovary cells and block HIV replication in virus infected H9 cells. However, this inhibition of HIV replication appears to be incomplete since virus replication occurs following removal of the toxin conjugates from these cultures. Moreover, CD4-PE conjugates delay but do not inhibit HIV replication in human peripheral blood lymphocytes. These studies suggest that such conjugates should be assessed only as potential adjunctive therapies in the acquired immunodeficiency syndrome. PMID- 2243140 TI - Arginine-glycine-aspartic acid- and fibrinogen gamma-chain carboxyterminal peptides inhibit platelet adherence to arterial subendothelium at high wall shear rates. An effect dissociable from interference with adhesive protein binding. AB - Arg-Gly-Asp (RGD)- and fibrinogen gamma-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa). GP IIb-IIIa, vWF, and Fn are essential for normal platelet adherence to subendothelium. We added peptides to normal citrated whole blood before perfusion over human umbilical artery subendothelium and evaluated platelet adherence morphometrically at high (2,600 s-1) and low (800 s-1) wall shear rates. We also examined the effects of the peptides on platelet adhesion to collagen in a static system. At the high wall shear rate, RGDS and GQQHHLGGAKQAGDV caused dose dependent reduction in the surface coverage with spread and adherent platelets. Amino acid transposition and conservative substitutions of RGD peptides and the AGDV peptide significantly inhibited platelet adherence at 2,600 s-1. By contrast, the modified RGD peptides and AGDV do not affect adhesive protein binding to platelets. None of the native or modified RGD- or fibrinogen gamma chain peptides significantly inhibited either platelet adherence to subendothelium at 800 s-1 or platelet adhesion to collagen. Our findings demonstrate that peptides that interfere with adhesive protein binding to GP IIb IIIa inhibit platelet adherence to vascular subendothelium with flowing blood only at high wall shear rates. Platelet adherence to subendothelium at high wall shear rates appears to be mediated by different recognition specificities from those required for fluid-phase adhesive protein binding or static platelet adhesion. PMID- 2243141 TI - Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease. AB - A membrane-bound cytochrome b, a heterodimer formed by a 91-kD glycoprotein (heavy chain) and a 22-kD polypeptide (light chain), is an essential component of the phagocyte NADPH-oxidase responsible for superoxide generation. Cytochrome b is absent in two subgroups of chronic granulomatous disease (CGD), an inherited disorder characterized by the lack of oxidase activity. Mutations in the cytochrome heavy chain gene, encoded by the CYBB locus in Xp21.1, result in the X linked form of CGD. A rare subgroup of autosomal recessive CGD also lacks cytochrome b (A- CGD), but the genetic defect has not previously been identified. In order to search for possible mutations in the cytochrome light chain locus, CYBA, the structure of this gene was characterized. The CYBA locus was localized to 16q24, and the approximately 600-bp open reading frame determined to be encoded by six exons that span approximately 8.5 kb. Three unrelated patients with A- CGD were studied for evidence of mutations in the light chain gene. One patient, whose parents were first cousins, was homozygous for a large deletion that removed all but the extreme 5' coding sequence of the gene. The other two patients had a grossly normal light chain transcript on Northern blot of mononuclear cell RNA. The light chain transcript was amplified by the polymerase chain reaction and sequenced. One patient was a compound heterozygote for two alleles containing point mutations in the open reading frame that predict a frame shift and a nonconservative amino acid replacement, respectively. The second patient, whose parents were second cousins, was homozygous for a different single base substitution resulting in another nonconservative amino acid change. These results indicate that A- CGD can results from defects in the gene encoding the 22 kD light chain of the phagocyte cytochrome b. PMID- 2243142 TI - Cholesterol synthesis is required for cutaneous barrier function in mice. AB - Previous studies have shown that topical acetone treatment results in the removal of stratum corneum lipids and disruption of the permeability barrier. This disruption stimulates epidermal lipid synthesis which is associated with the rapid restoration of stratum corneum lipids and barrier function. The aim of this study was to determine the role of cutaneous cholesterol synthesis in the barrier recovery. Here we show that topical lovastatin, a competitive inhibitor of HMG CoA reductase, inhibits cholesterol synthesis. After acetone disruption of the barrier, the normal rapid return of cholesterol to the stratum corneum and recovery of barrier function is impaired in animals treated topically with lovastatin. When lovastatin animals are simultaneously treated topically with either mevalonate, the immediate product of HMG CoA reductase, or cholesterol, the final end product of the pathway, the recovery of the barrier is normalized. Lovastatin resulted in the delayed secretion and abnormal appearance of lamellar bodies. These results provide the first evidence demonstrating that cholesterol synthesis is required for the maintenance of barrier structure and function and suggests a crucial role for cholesterol synthesis in allowing for terrestrial existence. PMID- 2243143 TI - Insulin regulates apolipoprotein B turnover and phosphorylation in rat hepatocytes. AB - Our laboratory has previously shown that insulin inhibits the secretion of newly synthesized and immunoreactive apo B from rat hepatocytes. We have also shown that apo B is secreted as a phosphoprotein and that phosphorylation is increased in hypoinsulinemic nonketotic diabetes. The present studies were conducted to determine whether the ability of insulin to inhibit apo B secretion is related to alterations in apo B turnover and whether insulin itself affects apo B phosphorylation. Pulse-chase studies with [35S]methionine in primary cultures of hepatocytes from normal rats in the absence and presence of insulin show that the secretion of apo B100 and apo B48 are inhibited by insulin and that this inhibition may be due in part to enhanced intracellular degradation. In addition, there is a second intracellular apo B48 pool which is not insulin regulated or degraded. In experiments in which hepatocytes were incubated with [32P]orthophosphate, insulin decreased 32P incorporation into apo B100 (42%) with only small effects on apo B48 (11%). The small insulin effect on apo B48 may relate to an insulin-insensitive apo B48 intracellular pool. These studies show that insulin can affect the intracellular turnover, secretion, degradation, and phosphorylation of apo B and emphasize the differential regulation of apo B100 and apo B48 with regard to these parameters in rat liver. PMID- 2243144 TI - Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy. AB - Schindler disease is a recently recognized infantile neuroaxonal dystrophy resulting from the deficient activity of the lysosomal hydrolase, alpha-N acetylgalctosaminidase (alpha-GalNAc). The recent isolation and expression of the full-length cDNA encoding alpha-GalNAc facilitated the identification of the molecular lesions in the affected brothers from family D, the first cases described with this autosomal recessive disease. Southern and Northern hybridization analyses of DNA and RNA from the affected homozygotes revealed a grossly normal alpha-GalNAc gene structure and normal transcript sizes and amounts. Therefore, the alpha-GalNAc transcript from an affected homozygote was reverse-transcribed, amplified by the polymerase chain reaction (PCR), and sequenced. A single G to A transition at nucleotide 973 was detected in multiple subclones containing the PCR products. This point mutation resulted in a glutamic acid to lysine substitution in residue 325 (E325K) of the alpha-GalNAc polypeptide. The base substitution was confirmed by dot blot hybridization analyses of PCR-amplified genomic DNA from family members with allele-specific oligonucleotides. Furthermore, transient expression of an alpha-GalNAc construct containing the E325K mutation resulted in the expression of an immunoreactive polypeptide which had no detectable alpha-GalNAc activity. PMID- 2243146 TI - Role of endothelium-derived nitric oxide in the bleeding tendency of uremia. AB - Endothelium-derived relaxing factor, now identified as nitric oxide (NO), is a labile humoral agent formed by vascular endothelial cells from L-arginine. NO mediates the action of substances that induce endothelium-dependent relaxation and plays a role in regulating blood pressure. In this study we investigated whether NO is involved in the pathogenesis of the bleeding tendency associated with renal failure. Rats with extensive surgical ablation of renal mass develop renal insufficiency due to progressive glomerulosclerosis. Like uremic humans, rats with renal mass reduction and uremia have a bleeding tendency that manifests itself by a prolonged bleeding time. We found that N-monomethyl-L-arginine (L NMMA), a specific inhibitor of NO formation from L-arginine, completely normalized bleeding time when given to uremic rats. L-NMMA injection also increased ex vivo platelet adhesion but did not affect ex vivo platelet aggregation induced by adenosine diphosphate, arachidonic acid, and calcium ionophore A23187. The shortening effect of L-NMMA on bleeding time was completely reversed by giving the animals the NO precursor L-arginine, but not D-arginine, which is not a precursor of NO. It thus appears that NO is a mediator of the bleeding tendency of uremia. PMID- 2243147 TI - Changes in the steady-state pharmacokinetics of theophylline during treatment with dirithromycin. AB - The steady-state plasma concentrations and pharmacokinetic characteristics of theophylline were studied during intermittent treatment with dirithromycin. The addition of dirithromycin (500 mg orally once daily at 7:00 AM) to a sustained release theophylline dosing regimen (200 mg every 12 hours) elicited small changes in the steady-state pharmacokinetics of theophylline. Mean steady-state plasma theophylline trough concentrations (Cmin) were invariant before, during, and after dirithromycin treatment; however, mean average steady-state plasma theophylline concentrations (Cav) declined by 18% during dirithromycin treatment (P less than .05), and mean peak plasma concentrations (Css,max) declined by 26% (P less than .01). Theophylline clearance (CL/F) exhibited an increase of comparable magnitude during dirithromycin treatment, although the increase in CL/F was not statistically significant (.05 less than P less than .1). Dirithromycin treatment alters the steady-state pharmacokinetics of theophylline; however, the magnitude of the changes is small and is not likely to modify treatment outcomes. PMID- 2243145 TI - L-tryptophan implicated in human eosinophilia-myalgia syndrome causes fasciitis and perimyositis in the Lewis rat. AB - Tryptophan-associated eosinophilia-myalgia syndrome (L-TRP-EMS) is a newly described syndrome which occurred in epidemic fashion in the United States in the summer and fall of 1989. Epidemiologic data has linked the syndrome to intake of L-tryptophan (L-TRP) from one specific manufacturer, but the precise etiologic compound(s) must be established by replication of the syndrome in an appropriate animal model. In this study, implicated L-TRP, United States Pharmacopeia (USP) grade L-TRP, or vehicle was administered by gavage in a blinded fashion for 38 d to female Lewis rats at doses comparable with those ingested by patients who developed the eosinophilia-myalgia syndrome. Animals receiving implicated L-TRP, but not those receiving USP grade L-TRP or vehicle, developed histologic signs consistent with fasciitis and perimyositis, specific pathologic features of human L-TRP-EMS. Peripheral blood eosinophilia was not observed. Hypothalamic corticotropin releasing hormone mRNA levels were lower and plasma corticosterone levels tended to be lower in the animals that received implicated L-TRP. Plasma L kynurenine was higher in both L-TRP-treated groups compared to the vehicle treated animals. The female Lewis rat is known to be susceptible to a wide variety of inflammatory diseases. Identification of specific inflammatory changes in this rat following exposure to implicated L-TRP indicates that this animal model will be important in subsequent investigations into the etiology, pathogenesis, and treatment of human L-TRP-EMS. PMID- 2243148 TI - Antihypertensive effects of a new sustained-release formulation of nifedipine. AB - The blood pressure response to a new sustained-release formulation of nifedipine was evaluated in an 8-week, double-blind, placebo-controlled study. Twenty-nine patients with mild essential hypertension were randomized to receive placebo (N = 9), 30 mg nifedipine (N = 10), or 60 mg nifedipine (N = 10). During treatment, 30 mg and 60-mg doses of nifedipine administered once daily decreased office blood pressures from 137/98 +/- 8/2 mm Hg and 141/98 +/- 15/2 mm Hg at baseline, respectively, to 126/89 +/- 9/7 mm Hg and 126/86 +/- 6/7 mm Hg (P less than .005). Noninvasive automatic ambulatory blood pressure monitoring demonstrated a marginally significant (P less than .10) reduction in the mean 24-hour blood pressure of 2/6 +/- 8/8 mm Hg and 5/6 +/- 9/9 mm Hg for patients taking 30 mg and 60 mg nifedipine once daily, respectively. Diastolic blood pressure load (the percentage of ambulatory diastolic blood pressure readings greater than 90 mm Hg) during 24 hours was decreased by 41% and 35%, with 30 mg and 60 mg nifedipine administered once daily, respectively. No significant dose response to nifedipine at these dose levels was observed. Although the once-daily formulation of nifedipine achieved effective control of office blood pressure, similar control was not observed in awake and 24-hour periods in all patients. PMID- 2243149 TI - Acute and steady-state pharmacokinetics and antihypertensive effects of felodipine in patients with normal and impaired renal function. AB - Eighteen patients (14 men and 4 women, aged 36-74 years) treated with metoprolol for a month were included in the study. Twelve had impaired renal function (IRF) with a glomerular filtration rate (GFR) of 7.5-77.1 mL/min and six having normal renal function (NRF) with a GFR of 84.9-113.0 mL/min. Plasma and urine concentrations of felodipine and metabolites, heart rate, and blood pressure were recorded over 24 hours on day 1 after an oral dose of 10 mg felodipine and 0.04 mg 3H-felodipine IV and repeated on day 29 during continuous treatment with felodipine, 10 mg bid. The bioavailability of the oral dose on day 1 and day 29 was 13% and 12.5%, respectively. The terminal plasma half-life (t1/2) on day 29 was 22 hours and systemic clearance was 490 mL/min on day 1 and 434 mL/min on day 29 (NS). There were no differences in these parameters between NRF and IRF. The protein binding determined by equilibrium dialysis in the six patients with the lowest GFR was 99.74% on day 1 and 99.73% on day 29 and did not differ significantly from previously reported values in healthy subjects. The mean supine blood pressure before the acute dose of felodipine was 164/96 mm Hg in the IRF patients and 145/95 mm Hg in the NRF patients. A maximum decrease of 37/22 mm Hg and 32/19 mm Hg, respectively, was seen within 1.5 hours after dose and at 12 hours the reduction was 12/9 and 15/10 mm Hg, respectively, compared to baseline values. At steady state the morning blood pressure before dose was 152/87 mm Hg in the IRF patients and 129/86 mm Hg in the NRF patients. Similar maximum decreases and effects at 12 hours were seen after dose on day 29 as on day 1. Data on the effect on diastolic blood pressure and plasma felodipine concentrations were well fitted to the Emax model. The maximum reduction in diastolic blood pressure using this model was 27% and the plasma concentration leading to 50% of the maximum effect was 6.2 nmol/L. In conclusion, renal disease does not affect the pharmacokinetics of felodipine. The pharmacokinetic and pharmacodynamic effects of felodipine are not altered during steady state. The renal excretion of inactive metabolites is reduced in IRF. However, the accumulation of metabolites in the blood does not affect the protein binding or the clearance of felodipine. No dosage adjustment of felodipine seems to be necessary in patients with hypertension and renal impairment. PMID- 2243150 TI - Metabolic effects of the combination of captopril and hydrochlorothiazide in hypertensive subjects. AB - The medium-term (16 weeks) effects of the combination of captopril and hydrochlorothiazide (HCTZ) on some metabolic indexes, particularly on plasma lipoproteins, were evaluated in 20 mild to moderate hypertensive outpatients. After a 4-week wash-out period, the subjects were given one tablet of a new commercially available fixed combination once/daily (i.e., captopril 50 mg + HCTZ 25 mg). The dose could be titrated to a maximum of one tablet twice daily according to individual blood pressure responses. Both systolic and diastolic blood pressure significantly decreased at week 4 and showed a further decrease thereafter; the rate of responders (diastolic blood pressure at or below 90 mm Hg at the end of the study) was very high (90%). The only metabolic change was a small though significant increase in HDL cholesterol (P less than .05), almost entirely due to an increase in the denser HDL3 subfraction. The atherogenic fractions, namely total cholesterol, LDL cholesterol, and apoprotein B, showed no significant changes. Plasma triglycerides underwent a transient increase at week 8 (P less than .05) but thereafter fell. Plasma glucose, creatinine, uric acid, and potassium were unchanged. The fixed combination of captopril and HCTZ seems highly effective in lowering blood pressure and seems devoid of untoward metabolic effects. Its overall impact on the coronary risk profile in hypertensive subjects seems therefore to be favorable. PMID- 2243151 TI - A simple method for the estimation of interaction bias in crossover studies. AB - The crossover trial is considered the most powerful means of determining the efficacy of new drugs. However this study design is frequently invalidated by treatment-by-period interaction. If, for example, the effect of the first treatment period carries on into the next one, then it influences the response to the latter period (carryover effect). A second problem is that there are no reliable statistical methods to test for this potential bias. This article takes issue with these problems and gives an alternative method for the detection of interaction simply by looking at the data. In a crossover without interaction the second period should be a true reflection of the first. If, however, the data of a treatment are better in the second period than in the first, a carryover effect is probable. If worse, a rebound phenomenon or a negative carryover effect is likely. If both treatments are better or worse, a time effect or some other external influence might be present. The authors illustrate this simple method by a summary of a few selected trials that have been published recently. This method enables not only the detection of interaction but also the differentiation between different types of interactions. Therefore, investigators are advised to use it in order to make sure that there are no unexpected problems. PMID- 2243152 TI - Clinical evaluation of diphenhydramine hydrochloride for the treatment of insomnia in psychiatric patients: a double-blind study. AB - The usefulness of the antihistaminic agent diphenhydramine hydrochloride was evaluated using a double-blind procedure at sleeping doses of 12.5, 25, and 50 mg in 144 psychiatric patients with insomnia. The general condition of the patients with insomnia was at least "slightly improved" in 62.5% (12.5-mg group), 60% (25 mg group), and 67.4% (50-mg group) after treatment with the test drug for 2 weeks. Side effects were observed in a total of 11 patients (7.6%) but were not severe. No symptoms suggestive of drug dependence were evident. Global improvement was not influenced by patient background factors except for the presence or absence of previous treatment for insomnia. The hypnotic effect of diphenhydramine hydrochloride was significantly greater in patients who had not been treated previously. A dose-dependent increase in the hypnotic effect was also seen in patients who had not received any previous treatment. Diphenhydramine hydrochloride thus appears to be effective in the treatment of insomnia, but the appropriate dosage will depend on previous medical treatment of insomnia. PMID- 2243153 TI - The correlation between predicted and measured patient specific analgesic concentrations after intravenous titration: a guide for initial maintenance requirements with methadone. AB - The relationship between the analgesic methadone concentrations measured and those predicted using a pharmacokinetic approach were assessed in 22 patients referred for long-term management of severe pain with intravenous methadone. Five milligrams of methadone were administered IV every 10 minutes until the patient reported a visual analog scale (VAS) pain score of less than or equal to 2. Initial maintenance infusion rates were chosen based on the number of 5 mg doses required to produce satisfactory analgesia. Overall, the methadone concentrations predicted using pharmacokinetic modeling were in excellent agreement with those actually measured. Over 95% of the variance in the data was explained using this model (r2 = 0.9704). Using the rapid titration paradigm described here, one can obtain a reasonable estimate of patient specific analgesic (target) concentration as well as initial infusion requirements for methadone. PMID- 2243154 TI - The CAST results. PMID- 2243155 TI - Pharmacologic therapy for arrhythmias: attention to the benefit-risk ratio. PMID- 2243156 TI - Globalization of the pharmaceutical industry: the physician's role in optimizing drug use. AB - In this new era of globalization, the physician must consider cultural differences in choosing methods of disseminating information so that practitioners in diverse settings may optimize drug usage. In addition, increasing competition, stimulated by the imminent unification of the European market in 1992, demands that the industry physician be concerned with developing possible new indications and cost-effective applications. These factors will enhance roles for the medical affairs physician in the pharmaceutical industry. PMID- 2243157 TI - Globalization of the pharmaceutical industry: the physician's role in evaluating drug safety. AB - The trend toward uniformity of drug registration procedures due to imminent European Economic Community globalization has encouraged pharmaceutical companies to conduct studies on a worldwide basis. This standardization of methods will facilitate the "poolability" of efficacy and safety data generated by these international studies into a common database. With the internationalization of the pharmaceutical marketplace, physicians in industry may be required to collect and interpret such reports from all over the globe. The globalization of the pharmaceutical industry will thus broaden the opportunities for physician involvement in safety detection. PMID- 2243158 TI - Intraperitoneal administration of acyclovir in patients receiving continuous ambulatory peritoneal dialysis. AB - In subjects with normal renal function, acyclovir is rapidly removed from the body via the kidneys. In subjects with end-stage renal disease, the half-life is significantly prolonged. The half-life in subjects receiving hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) is similarly prolonged (10.0 +/- 2.2 and 13.2 +/- 4.7 hours, respectively). After intravenous dosage, peritoneal clearance was 3.4 +/- 0.2 mL/min. Intraperitoneal dosing in subjects receiving CAPD resulted in a bioavailability of 61 +/- 10% and drug levels sufficient to inhibit herpes simplex virus (HSV) and varicella zoster virus (VZV). Intraperitoneal administration is an alternative route of administration in patients with poor vascular access. PMID- 2243159 TI - Visual receptive field organization and cortico-cortical connections of the lateral intraparietal area (area LIP) in the macaque. AB - The visual receptive field physiology and anatomical connections of the lateral intraparietal area (area LIP), a visuomotor area in the lateral bank of the inferior parietal lobule, were investigated in the cynomolgus monkey (Macaca fascicularis). Afferent input and physiological properties of area 5 neurons in the medial bank of the intraparietal sulcus (i.e., area PEa) were also determined. Area LIP is composed of two myeloarchitectonic zones: a ventral zone (LIPv), which is densely myelinated, and a lightly myelinated dorsal zone (LIPd) adjacent to visual area 7a. Previous single-unit recording studies in our laboratory have characterized visuomotor properties of area LIP neurons, including many neurons with powerful saccade-related activity. In the first part of the present study, single-unit recordings were used to map visual receptive fields from neurons in the two myeloarchitectonic zones of LIP. Receptive field size and eccentricity were compared to those in adjacent area 7a. The second part of the study investigated the cortico-cortical connections of area LIP neurons using tritiated amino acid injections and fluorescent retrograde tracers placed directly into different rostrocaudal and dorsoventral parts of area LIP. The approach to area LIP was through somatosensory area 5, which eliminated the possibility of diffusion of tracers into area 7a. Unlike many area 7a receptive fields, which are large and bilateral, area LIP receptive fields were much smaller and exclusively confined to the contralateral visual field. In area LIP, an orderly progression in visual receptive fields was evident as the recording electrode moved tangentially to the cortical surface and through the depths of area LIP. The overall visual receptive field organization, however, yielded only a rough topography with some duplications in receptive field representation within a given rostrocaudal or dorsoventral part of LIP. The central visual field representation was generally located more dorsally and the peripheral visual field more ventrally within the sulcus. The lower visual field was represented more anteriorly and the upper visual field more posteriorly. In LIP, receptive field size increased with eccentricity but with much variability with in the sample. Area LIPv was found to have reciprocal cortico-cortical connections with many extrastriate visual areas, including the parieto-occipital visual area PO; areas V3, V3A, and V4: the middle temporal area (MT); the middle superior temporal area (MST); dorsal prelunate area (DP); and area TEO (the occipital division of the intratemporal cortex). Area LIPv is also connected to area TF in the lateral posterior parahippocampal gyrus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2243160 TI - Ultrastructure of the electrotonic and chemical components of the lateral-to motor and medial-to-motor synapses in crayfish nerve cord. AB - Lateral-to-motor and medial-to-motor synapses in crayfish nerve cords are composed of an electrical and a chemical component. The presynaptic terminals showed localized clusters of synaptic vesicles, electron-dense areas, coated pits, and coated vesicles. In thin sections, active zones were defined by electron-dense regions where synaptic vesicles attached and, in freeze-fracture replicas, by clusters of intramembrane particles localized in bands with vesicle openings on the sides of these bands. The cytoplasmic surface of the postsynaptic membrane opposite the active zones was coated with electron-dense material that in freeze-fracture replicas was seen as an increase in intramembrane particles located in the external leaflet (EF-face). This specialization of the postsynaptic membrane may correspond to the neurochemical receptor. Also, pre- and postsynaptic membranes were separated by a wider extracellular gap than those of adjacent nonsynaptic regions and electrical synapses or gap junctions. Synaptic vesicles were located exclusively at the synaptic regions by means of a cytoskeleton that was different for the electrical and the chemical components. The vesicles associated with the electrical component were anchored to a cytoskeleton composed of a beaded layer of densities located parallel to the membrane. This cytoskeleton maintained the synaptic vesicles separated from the presynaptic membrane by a distance of 13 +/- 2 nm. The synaptic vesicles associated with the chemical component were anchored to electron-dense regions formed by filaments arranged in bundles, anchored to the presynaptic membrane. Vesicles lined both sides positioned to discharge their contents into the extracellular space and to replace the discharged vesicles. PMID- 2243161 TI - Failure of the subcallosal sling to develop after embryonic X-irradiation is correlated with absence of the cavum septi. AB - During embryonic development of the rodent forebrain, a cavity normally appears at the midline just below the corpus callosum. This cavity, the cavum septi, is present in mice by gestational day 18, but is subsequently obliterated by growth of the septal nuclei and neuropil. After x-irradiation of pregnant mice with 125r on gestational day 14.5, the cavum septi did not develop. This dramatic developmental abnormality was accompanied by delayed fusion of the septum, and a reduction in the population of subventricular cells that normally migrate to form a sling of cells extending from the medial aspect of the lateral ventricles to the midline. In normal animals formation of the cavum septi involves degeneration of this subcallosal sling of SV cells. Thus absence of the cavum after x irradiation may be due to the premature killing of subventricular cells before their migration toward the midline. PMID- 2243162 TI - Distribution of lumbar dorsal root fibers in the lower thoracic and lumbosacral spinal cord of the rat studied with choleragenoid horseradish peroxidase conjugate. AB - Spinal cord projections from lumbar dorsal root ganglia (DRGs) were investigated in adult rats following injections of choleragenoid horseradish peroxidase (B HRP) into each of the six lumbar DRGs. This method is known to label primarily thick fibers. Labeling was found in all laminae except in the outer part of lamina II. Labeled fibers and terminal-like structures were found 8-13 segments rostral and 1-5 segments caudal to the injected DRGs. A somatotopic organization was revealed in laminae III, where the labeling seemed to be organized in mediolateral zones. Some of these protruded as fingerlike processes through segments rostral and caudal to the root entry level. An interdigitating pattern for these fingerlike processes was seen between some DRGs, while an extensive overlap was found between other DRGs. Many zones were found to correspond to the known central projections of peripheral sensory nerves supplied by the injected ganglion. This suggests that the central projection of a DRG is highly related to the projections of the peripheral nerves included in the DRG. The projections to lamina IV were organized in a similar manner as in lamina III, even though the projections showed a higher degree of overlap than in lamina III. No clear somatotopic organization was found in laminae V-IX. Provided that the topographical relationship between central projections of single peripheral nerves and of DRGs correspond to their peripheral projections, the results of this study, together with results of earlier studies suggest that the outlines of dermatomes are highly related to the territories of peripheral nerves included in the dermatomes. PMID- 2243165 TI - The Indiana pouch: a continent urinary diversion. PMID- 2243164 TI - Skin care considerations in the neonate for the ET nurse. PMID- 2243163 TI - Ultrastructure of cholinergic synaptic terminals in the thalamic anteroventral, ventroposterior, and dorsal lateral geniculate nuclei of the rat. AB - The principal relay nuclei of the thalamus receive their cholinergic innervation from two midbrain cholinergic groups: the pedunculopontine tegmental nucleus and the laterodorsal tegmental nucleus. The different thalamic nuclei exhibit populations of cholinergic axons which vary in density and morphology when examined at the light microscopic level. However, the ultrastructure of the cholinergic terminals in different thalamic nuclei has not been described. This study was undertaken to confirm that synaptic contacts are formed by cholinergic axons in several principal thalamic relay nuclei, to describe their ultrastructural morphology, and to identify the types of postsynaptic elements contacted by cholinergic synaptic terminals. The thalamic nuclei examined in this study are the dorsal lateral geniculate nucleus, ventroposteromedial nucleus, ventroposterolateral nucleus, and anteroventral nucleus. Our results confirm that cholinergic axons form synaptic terminals in these thalamic nuclei. Cholinergic synaptic terminals contact structures outside the characteristic synaptic glomeruli, are never postsynaptic, and have morphologies and postsynaptic targets which differ among the thalamic nuclei. In the ventroposterior nuclei, cholinergic terminals form asymmetric synaptic contacts onto larger dendrites in the extraglomerular neuropil. In the anteroventral nucleus, cholinergic terminals form both symmetric and asymmetric synaptic contacts onto dendrites and somata. Cholinergic terminals in the anteroventral nucleus are larger than those in other nuclei. In the dorsal lateral geniculate nucleus, cholinergic terminals contact both somata and dendrites in the extraglomerular neuropil, but the synaptic contacts in this nucleus are symmetric in morphology. PMID- 2243166 TI - Universal pressure sore precautions. PMID- 2243167 TI - A collaborative study: evaluation of a postoperative pouching system. PMID- 2243168 TI - Teaching ostomy care to nursing students. PMID- 2243169 TI - Stresses produced during application of ostomy pouches. PMID- 2243170 TI - Enhanced degradation of carbofuran in Pacific Northwest soils. AB - Persistence of 14C-carbonyl carbofuran was measured in Pacific Northwest soils that had received 1-14 applications of the insecticide for root weevil control on perennial crops. Insecticide decay curves were obtained in nonautoclaved soil and several autoclaved soil samples from previously-treated fields and in nonautoclaved soils from paired control sites not previously treated with carbofuran. The insecticide usually degraded faster in soil from previously treated fields than in soil from corresponding control fields. Among 26 previously-treated fields, the pseudo half-life (time for 50% loss) of carbofuran was less than one wk in 11 soils, 1-3 wks in 8 soils and greater than 4 wks in the remaining soils. Among the nontreated control fields the pseudo half-life was greater than 2 wks in all cases and greater than 15 wks in 5 of the soils. The carbofuran decay curve always possessed an initial lag phase where soil mixing enhanced insecticide decline. Carbofuran degraded very slowly in autoclaved soil samples. The half-life of carbofuran exceeded 16 wk in all autoclaved soils tested and in most instances 85-90% of the original dosage remained when the tests were terminated 112 days after treatment. These results provided evidence that many of the soils which received applications of carbofuran over the past several years have developed a capacity to degrade carbofuran very rapidly. PMID- 2243171 TI - Sorption mechanism of DDT from aqueous phase. AB - Sorption is one among the many techniques available for the removal of organic materials from potable water and waste water. Use of locally available Wood Charcoal (WC) is essential in place of costly activated charcoal to make the process more economical and lucrative. The vital objective of this investigation was to assess the performance of WC for the removal of DDT from the aqueous phase. The influence of important factors like, particle size, pH, and time of contact, which affects the sorption process was studied in this investigation using batch experiments. The removal kinetics were carried out under the temperature 27 degrees +/- 1 degrees C (room temperature) and the sorption kinetics constants were evaluated. Sorption equilibria study has also been carried out to develop the Freudlich's sorption isotherm equation from which the ultimate sorption capacity of WC for sorption of DDT was calculated. PMID- 2243172 TI - Bioaccumulation of endosulfan (Thiodan insecticide) in the tissues of Louisiana crayfish, Procambarus clarkii. AB - The bioaccumulation potential of endosulfan was determined by constantly exposing male and female adult crayfish, Procambarus clarkii to 100 ppb Thiodan insecticide for 8 wks. The crayfish were removed at 2 wk intervals and the uptake by tissues (whole-body) was determined by electron capture gas-chromatography. The same number of pre-exposed crayfish (100 ppb Thiodan) were transferred to endosulfan-free water after 8 wks, and insecticide loss (depuration) was similarly quantitated. The maximum amount of insecticide and its metabolites detected after 8 wks were 197 ppb endosulfan II, 18 ppb endosulfan I and 3 ppb endosulfan sulfate. During the first 4 wks of depuration, endosulfan loss from cryfish tissues occurred rapidly, and only 3 ppb endosulfan I remained. No endosulfan II and sulfate were detected beyond 4 wks. The residues in male vs female were not significant statistically. Bioaccumulation factor (BF) for endosulfan II for crayfish tissues was 1.97, which is considerably lower than for other aquatic invertebrates (26 for scallop, Chlamys opercularis and 600 for mussel, Mytilus edulis. The presence of endosulfan sulfate in the tissues cannot be considered as 'detoxification' which is as toxic as the parent compound. PMID- 2243173 TI - Yielding to age: when the elderly can no longer drive. AB - Loss of ability to drive because of declining health is a symbolic and concrete representation that the person is no longer capable of performing as he or she once did. Grieving the loss of the ability to drive is complex in that driving is associated with many interactions, such as freedom, esteem, identity, and control. Families may be reluctant to address the ability to drive safely because of fear of confrontation and their own grieving at the loss it symbolizes. Resolution of the loss of the ability to drive depends on the family's and individual's ability to work through the grieving process, concurrent losses, cognitive abilities, and the availability of resources. PMID- 2243174 TI - Behavior management training for nurse aides: is it effective? AB - Nursing assistants are responsible for 80% to 90% of all direct resident care in nursing homes, but are the least well trained personnel. Even with currently mandated training, specific skills to meet mental health needs are not taught. Training in behavior management skills prepares aides to observe and respond to problem behaviors more effectively. Aides view their own use of skills as increased by this training. To be practically useful, mental health training programs for nurse aides should be provided by professional personnel in brief, concrete, self-contained units that model the skills they present. PMID- 2243175 TI - Essential factors in a community college-nursing home partnership. AB - The community college-nursing home partnership has two major objectives: to develop nursing potential in long-term care settings and to influence the redirection of associate degree nursing education to include active participation in long-term care settings. Successful partnerships are built on a commitment to high quality education for students and high quality service for patients. Other essential factors to a successful partnership include collaborative planning, pragmatic goal setting, clear communication, and mutual respect. PMID- 2243176 TI - A challenge for nursing: promotion of self-care among the elderly. PMID- 2243177 TI - Discovering the secret. Nursing assessment of elderly alcoholics in the home. AB - Comprehensive functional assessment of the older alcoholic is needed because of the complex needs of the aged. Signs of alcohol abuse may be more obscure for older drinkers than for younger age groups. Signs of alcohol abuse are often accepted as signs of aging. Older drinkers remain socially isolated more often than younger drinkers. Many older alcoholics will eliminate or moderate their drinking once they understand how abuse will affect their well-being. PMID- 2243178 TI - Nursing home placement: the daughter's perspective. AB - The decision for nursing home placement of a parent has been identified as one of the most difficult decisions for adult children to make. These decisions are made in a family context and are characterized by moral dilemmas. Expressions of loss of attachment or bonding, desires to maintain affective roles with parents following admission, and hurt avoidance for parents, family, and self appear in the decision for nursing home placement and are carried through into the actual admission. Knowledge about adult daughter's perceptions surrounding the decision for nursing home placement can aid nursing staff in anticipatory socialization for daughter and parent. Involvement of daughters in the decision for placement and the period immediately after admission could promote family interactions, foster trust in building relationships with the staff, and possibly decrease the incidence of relocation to other nursing homes. PMID- 2243179 TI - Role of breast-feeding in the prevention and treatment of diarrhoea. AB - Recent studies have again shown the beneficial effects of breast-feeding in preventing morbidity and mortality from diarrhoea in infants. A case-control study in Brazil has shown that young infants who are not breast-fed have a 25 time greater risk of dying of diarrhoea than those who are exclusively breast fed. A longitudinal study in the urban slums of Lima, Peru found that exclusively breast-fed infants have a reduced risk of diarrhoeal morbidity when compared with infants receiving only water in addition to breast-milk. Both these studies, along with numerous others in developing countries, point to the need to extend the duration of exclusive breast-feeding to at least 4-6 months. A review of concerned studies throughout the world shows that even in malnourished women, breast-milk output is sufficient to maintain growth of infants up to this age. The addition of early food supplements to infants fed under prevailing environmental conditions in developing countries leads to their increased diarrhoeal attacks and associated reduced food intake. This results in worsened nutritional status of the affected infants. Breast-feeding helps maintain hydration status during diarrhoeal episodes. Studies in Peru, India, and Nigeria have shown that breast-feeding can be continued during diarrhoea when the infants often refuse other foods, specially non-human milk. Thus, breast-feeding is important in providing necessary calories and protein during a time when a loss of appetite for other foods is common. Diarrhoeal disease control programmes need to modify service delivery to ensure that breast-feeding mothers are not separated from their infants while being treated with oral rehydration therapy (ORT) as inpatients or outpatients. Oral rehydration solution (ORS) should be given to infants with cup and spoon rather than bottles, in order not to interfere with suckling. When in a health system bottles are used for treatment, an implicit credibility is given to their role in modern treatment. Programmes also need to include breast-feeding promotion as a part of their activities. This should comprise hospital practices supporting and ensuring breast-feeding immediately after delivery of the infants and subsequently while they are treated in the hospital: immediate breast-feeding after delivery; Mothers and infants rooming together; On demand breast-feeding; No bottle feedings of water or infant formula; No pre-lacteal feeds. In addition, health professionals need to understand the skills for the management of breast-feeding, so that mothers are given appropriate advice on how to breast-feed and counteract breast-feeding problems. PMID- 2243181 TI - Rotavirus infection in children hospitalised with diarrhoea in Sri Lanka. AB - Seasonal and clinical aspects of rotavirus-associated diarrhoea in 98 of the 326 children hospitalised for diarrhoea are described. Rotavirus infection was detected (30% overall) throughout the year from May 1980 to April 1981, but the prevalence was higher during the rainy season (40-50%). The age group in which rotavirus was detected most frequently was from 4 months to 2 years (34.6%). Watery diarrhoea and vomiting were significantly commoner in children with rotavirus diarrhoea (75% and 71% respectively) than those with non-rotavirus diarrhoea (54.2% and 60.8% respectively; p less than 0.05). Although about 15% of the children with rotavirus-associated diarrhoea showed blood or mucus in stools, the invasive nature of rotavirus infection cannot be drawn since the study did not include tests to detect other diarrhoeal pathogens. PMID- 2243180 TI - Comparison of latex agglutination test with an ELISA to diagnose rotavirus associated diarrhoea in infants and young children. AB - An agglutination (LA) test, using latex beads sensitised with anti-rotavirus immunoglobulin G, was evaluated to detect human rotavirus in 200 stool specimens by comparing its results with those of an ELISA (Rotazyme, Abbott Laboratory, Diagnostic Div., North Chicago, IL). The specimens were collected from a systematic sample of 200 infants and pre-school children attending the Diarrhoeal Disease Research and Rehydration Centre at the Bab-El-Sha'reya University Hospital, Egypt. Of the 200 stool specimens tested, 79 were positive by the ELISA and 68 were positive by the LA test. Taking the ELISA as the standard, the LA test showed 11 false-negative and six false-positives giving a sensitivity and specificity of 86% and 95% respectively. Using 48 stool specimens positive for rotavirus by both the tests, the degree of positivity of the LA test roughly showed a linear relationship with the degree of rotazyme optical density. Thus, the simple and inexpensive LA test may be useful as a screening procedure to detect rotaviruses in the stools of children with diarrhoea. PMID- 2243182 TI - A cholera outbreak associated with eating uncooked pork in Thailand. AB - In a village near Chiangmai, Thailand, during October 1987, there was an outbreak of cholera following a funeral in which 264 attendants were served food. The present article is a report of an epidemiological study performed to identify the source of infection and the mode of its transmission. All the attendants were screened for infection by bacteriological examination of their rectal swabs and were kept under diarrhoeal surveillance. Of them, 20 patients and 40 matched controls were interviewed about the details of their eating foods served at the funeral. Vibrio cholerae 01, Inaba, El Tor was detected from 24 persons (9.1%), 15 of whom suffered from mild diarrhoea and the rest 9 had inapparent infections. There was no death. Except one butcher whose rectal swab was positive for the same strain of V. cholerae, 3 other butchers and 4 women who had prepared food were free from the infection. Food remnants were not available for culture. The water used for cooking and the water from the cement well used for slaughter were negative for the organism. The only significant association (p less than .01, odds ratio = 15) was found between an attack of cholera and eating laebmoo--an uncooked pork preparation with Thai spices and chili. The transmission of cholera appeared to have occurred through eating the uncooked pork presumably due to its contamination with V. cholerae shed by the infected butcher. He was known to have earlier visits to Chiangmai where cholera epidemic was going on. PMID- 2243183 TI - An outbreak of food poisoning due to Salmonella typhimurium in the People's Republic of China. PMID- 2243184 TI - Multi-drug-resistant Shigella infections in Fujian Province, China. PMID- 2243185 TI - [Experiments of contamination with bacteria while transfusion between the newly developed porous polymer plug and by air needle plug]. AB - We newly developed a transfusion plug that has an air passage of polymer porous material (I Cap). This porous polymer material theoretical does not pass the infectious microorganisms. We experimented contaminations during the transfusions by I Cap and that using air needles. Trypticated soy broth was used for the experiments. Experiments of transfusion in a dusty environment revealed that the transfusions by air needles got 100% contamination and that by I Cap was 0%. The experiments in a clinic room transfusions also revealed that air needle resulted in 30.3% contamination but on the contrary 0% with the I Cap. Dusty air was flown under high pressure (1.5 atmospheric pressure) through the same filter of I Cap for 30 minutes into the trypticated soy broth. These experiments revealed that the filter did not permeate bacteria and that transfusions with air needle was contaminated with dust. PMID- 2243186 TI - [A case of Legionnaires' disease, the first case in Hokkaido Prefecture--an experience of isolation of Legionella pneumophila and identification by indirect immunofluorescence antibody method]. AB - Although 18 cases of Legionnaires' disease have been reported in Japan, these have included none from the northern areas of Japan. The first confirmed case of Legionnaires' disease in Hokkaido district, a northern island of Japan, is reported. A 48 year-old male was admitted for fulminant pneumonia, and died the next day. Legionella pneumophila, serogroup 1, was cultured and determined from the sputum and lung tissue obtained at autopsy. Postmortem examination by means of the indirect immunofluorescent method, using group specific antisera against Legionella pneumophila as a primary antibody, revealed phagocytized bacilli in the alveoli of the lung. PMID- 2243187 TI - [Comparison between two systems for assaying the level of antibody against Streptococcus agalactiae (GBS) type III]. AB - Levels of antibody against GBS type III in pregnant women have been determined using ELISA assay method that we originally deviced. Toyo Jozo Co. have also introduced an assay system (the Toyo kit) that resembles ours. The present study was performed to compare our system with the Toyo kit. Correctivity between the two systems was good, giving a regression curve of Y = 1.18X - 0.60 and a correlation coefficient of r = 0.794. Antibody levels in pregnant women were determined by the Toyo kit, and were found to be less than 10 micrograms/ml in almost all samples. Among 19 serum samples from vaginal carriers of GBS type III, the antibody levels ranged from 1.5 to 93.8 micrograms/ml. Among seven maternal serum samples in cases of GBS type III infection, the maximum level was 6.0 micrograms/ml. Thus, the Toyo kit showed satisfactory sensitivity for determining the level of antibody against GBS type III. Hereafter, we intend to use the Toyo kit for determining antibody levels in pregnant women. PMID- 2243188 TI - [Investigation of Chlamydia trachomatis pneumonia in children]. AB - A neonatal pneumonia caused by Chlamydia trachomatis (C. trachomatis) is well known. But it is uncertain whether C. trachomatis causes pneumonia in a patient over 1 year of age. Therefore, a search for serologic and cultural evidence of C. trachomatis infection in patients suffering from acute pneumonia over 1 year of age was made. We studied 183 children ages 1 to 5 year-old suffering from acute pneumonia admitted to Kousei General Hospital to assess the relation between acute pneumonia and C. trachomatis. We investigated the serologic evidence of acute C. trachomatis infections in 73 children with a persistent cough and wheezing, detecting specific IgG antibodies and IgM antibodies by microimmunofluorescence test. Serologic results signifying acute infection were observed in 4 cases (2.2%). Then we tried to isolate C. trachomatis from the cultures of nasopharyngeal swabs, specific inclusion bodies of C. trachomatis in 2 cases (1.1%) were found. Our study suggests that C. trachomatis might cause pneumonia in children over 1 year of age. PMID- 2243189 TI - [Studies on relationships between the inhibition of human neutrophil NADPH oxidase by anti-inflammatory drugs and development of bacterial infections]. AB - The effects of anti-inflammatory drugs (acetylsalicylic acid, ASA; salicylic acid, SA; indomethacin, IM; hydrocortisone, HC) on the respiratory burst oxidase (NADPH oxidase) from human neutrophils in both whole cell and fully soluble (cell free) systems were investigated. These drugs were found to inhibit the superoxide generation by human neutrophils exposed to phorbol myristate acetate in a whole cell system and the activation of superoxide-generating NADPH oxidase by sodium dodecyl sulfate in cell-free systems. Concentrations of these drugs required for 50% inhibition of the oxidase (ID50) were; ASA (more than 3.0 mM in the whole cell system and 1.35 mM in the cell-free system), SA (more than 3.0 mM in the whole cell system and 1.30 mM in the cell-free system), IM (180 microM in both systems) and HC (50 microM in the whole cell system and 40 microM in the cell free system). In addition, these drugs time-dependently inhibited the activation of NADPH oxidase in cell-free systems. In the cell-free system, all of the drugs did not change the Km values for NADPH of the oxidase. These results suggest that these anti-inflammatory drugs, especially HC and IM, inhibit the reconstitution (activation) of neutrophil NADPH oxidase enzyme in the cell-free (whole cell) system. PMID- 2243190 TI - [Clinical studies on mycosis especially deep-seated candidiasis in blood disorder patients]. AB - Deep-seated mycosis is prominently increasing as a terminal infection in compromised hosts with malignant blood disorders or malignant tumors. Moreover, localized candidal abscess of visual organs has recently been reported in several laboratories. We investigated the occurrence of deep-seated mycosis in 105 autopsied cases with blood disorders in our clinic from 1980 to 1987. Forty-four of those cases had died of various infections, and 80% of them were fungal infections. More than half of the fungal infections were aspergillosis. Deep seated candidiasis was recognized in 10 cases, 6 of which were systemic candidiasis, the average duration of neutropenia below 500/mm3 was 19.7 days that of lymphopenia was 36.5 days. Two cases were complicated with GI-tract ulcer, and involved with hepatic candidiasis. On the other hand, in the 4 cases of localized candidial abscess, the duration of neutropenia was 58.5 days and that of lymphopenia was 28.8 days. These four cases were complicated with GI-tract ulcer. Histologically, Candida spp. were recognized at the bottom of the ulcer and invasion by inflammatory cells or tumor cells was found in the portal vein. We surmised that GI-tract ulceration is a very important complication of hepatic candidiasis or liver abscess, and the occurrence of localized candidiasis seems to depend on the duration and severity of neutropenia. PMID- 2243191 TI - [Human respiratory tract infection by Pasteurella multocida subsp. multocida presumably derived from the cat]. AB - Pasteurella multocida is a Gram-negative short rod-shaped bacteria that has been recognized as a pathogen of hemorrhagic septicemia and fowl cholera in the veterinary medicine. Infections by this microorganism as seen in the foreign literature vary widely from local infections due to bites and scratches by animals to general infections such as infections of the respiratory tract, sepsis, and meningitis. In Japan, reported cases of P. multocida infections are predominantly local infections, followed by respiratory infection. Recently, death of diabetic patients due to septicemia by this pathogen has also been reported. In this study, we experienced a case of respiratory tract infection in which the pathogen P. multocida subsp. multocida was suggested to have been transmitted from a pet cat by the agreement of the serotype of the bacterial isolates between the patient and the cat. This case was evaluated from the zoonotic viewpoint. The patient was a 68-year-old male who had been followed up since 1982 with a diagnosis of bronchiectasis. After his referral to our hospital, P. multocida subsp. multocida was isolated from his bloody sputum and, then, from the cat kept by the patient. The tow isolates were identical in terms of the biochemical properties, drug susceptibility profile, and serotype (-:1), and the derivation of P. multocida subsp. multocida infection from cat was established for the first time in this report. The incidence of P. multocida infections is increasing in Japan, and particular attention is considered to be needed about these conditions as zoonoses as indicated in "Preventive Measures against Zoonoses Derived from Pet Animals (Dog, Cat)", an official communication from the Ministry of Health and Welfare to related institutions in 1989. Also, to check whether the patient keeps any pet at the clinical inquiry is a practice of bacteriological importance in all fields of medicine. PMID- 2243192 TI - Maternally derived antibodies to Japanese encephalitis virus in cattle. AB - Serum samples were collected from 55 pairs of calves that had not passed the first summer and their dams reared in Kagoshima from 1983 through 1985. They were investigated for the HI antibody to Japanese encephalitis virus (JEV) in calves and for the correlation of antibody levels between calves and their dams. The maternally derived antibody was detected in 35 of 55 calves (63.6%), showing the mean antibody titer of 12.4. A significant negative correlation (p less than 0.01) was noted between the age of calve and titer of passively acquired antibodies. The regression equation suggested that the maternal antibody disappeared from the calf serum at about 3 months of age. On the other hand, 37 of 55 dams (67.3%) were positive for HI antibody to JEV, and the mean titer of the antibody was 12.7. There was a significant correlation (p less than 0.01) in serum antibody titers between dams and their calves. PMID- 2243194 TI - [Studies on respiratory infections in primary care clinic (IV). Antibiotic sensitivity of bacteria isolated from patients with respiratory infections visiting 21 private clinics in the Tohoku District of Japan]. AB - We determined the MICs of ampicillin, methicillin, cefaclor, cefixime, cefteram, ofloxacin and ciprofloxacin against a total of 1,448 strains from 11 species: 464 strains of Staphylococcus aureus, 306 strains of Streptococcus pneumoniae, 114 strains of Streptococcus pyogenes, 37 strains of Branhamella catarrhalis, 329 strains of Haemophilus influenzae, 32 strains of Escherichia coli, 66 strains of Klebsiella pneumoniae, 26 strains of Enterobacter cloacae, 20 strains of Serratia marcescens, 12 strains of Pseudomonas aeruginosa and 42 strains of Acinetobacter calcoaceticus, isolated from the throat swab and the sputum of 2,539 patients with respiratory infections who visited 21 private clinics in Tohoku district of Japan during the period from January to April in 1989. Ciprofloxacin and ofloxacin were more active against S. aureus, B. catarrhalis, P. aeruginosa and A. calcoaceticus than other antibiotics. Ampicillin and cefteram were more active against S. pneumoniae and S. pyogenes than other antibiotics. New-quinolones and cephems of new-generation were active against H. influenzae, E. coli, K. pneumoniae, E. cloacae and S. marcescens. Of 30 strains of S. aureus which were resistant (MIC greater than or equal to 12.5 micrograms/ml) to ampicillin, only one strain was resistant (MIC greater than or equal to 12.5 micrograms/ml) to methicillin. Twenty strains (6.5%) of S. pneumoniae and 49 strains (14.9%) of H. influenzae were resistant (MIC greater than or equal to 1.56 micrograms/ml) to ampicillin. Of 101 strains of H. influenzae of which their beta-lactamase activity was determined by Nitrocephin-method, 27 (26.7%) were beta-lactamase positive strains. The above results indicated that MRSA is only rarely found in primary care clinics but the incidence of ampicillin-resistant H. influenzae in primary care clinics is almost the same as that of the intensive care clinic, i.e. medical school-affiliated hospitals. Therefore caution should be exercised as regards antibiotic resistance of the causative organism even in primary care clinics. PMID- 2243193 TI - [Studies on respiratory infections in primary care clinic (III). Distribution of bacteria isolated from patients with respiratory infections visiting 21 private clinics in the Tohoku District of Japan]. AB - The bacteriology of the isolates from the throat swab and the sputum respectively of 2,539 patients with respiratory infections visiting 21 private clinics in Tohoku district of Japan during the period from January to April in 1989 was documented. Of the 2,539 patients, 1,694 had an acute upper respiratory infection, 609 had acute bronchitis, 46 had acute pneumonia, 84 had acute exacerbation of chronic respiratory infections and 106 had respiratory infections without diagnosis registered. 1887 (74.3%) strains of potential pathogens were recovered from 1507 (59.4%) of the 2539 cases. The rate of recovery of potential pathogens was very high in patients of the younger age. These patients had elevated body-temperature. There were statistically significant differences in recovery rate when classified by diagnosis, prefecture and the period of investigation. Of the 1,887 strains, 996 (52.8%) were gram-positive and 891 (47.2%) were gram-negative bacteria. The rate of recovery of gram-negative bacteria was high in patients who were less than 10 years old and more than 51 years old, in patients with pneumonia and chronic respiratory infections, and in patients with fever. Of the 1,887 strains, those which exceeded 100 were Staphylococcus aureus (481 strains), Haemophilus influenzae (340 strains), Streptococcus pneumoniae (329 strains), Streptococcus pyogenes (117 strains) and Acinetobacter spp. (100 strains). Species other than those mentioned above had less than 100 strains. In this group there were 39 strains of Branhamella catarrhalis, 32 strains of Escherichia coli, 97 strains of Klebsiella spp., 40 strains of Enterobacter spp., 25 strains of Serratia spp., 12 strains of Pseudomonas aeruginosa and 43 strains of Pseudomonas putida. There was a remarkable difference in recovery rate of each species when classified by diagnosis, age class, prefecture and the period of investigation, respectively. The above results indicated that gram-positive bacteria are more frequent than gram-negative bacteria, that enterobacteriaceae and glucose-non-fermentative gram negative bacteria are only rarely found in primary care clinics, and that the bacteriology in primary care clinic is different from that of medical school affiliated hospitals. PMID- 2243196 TI - [Two cases of psittacosis accompanied with rhabdomyolysis]. AB - We experienced two cases of atypical pneumonia accompanied with rhabdomyolysis and diagnosed them as psittacosis based on the results of investigation of paired serum samples. Rhabdomyolysis may be associated with some kinds of viral or bacterial infections, but no report was found in the case of psittacosis as far as we searched and such a description was not found in textbooks. Heretofore, the elevation of GOT and LDH as the laboratory findings in psittacosis was considered as the reflection of liver injury, but that might be brought about by rhabdomyolysis. Although the mechanism(s) of the occurrence of rhabdomyolysis in psittacosis is unknown, when the elevation of muscular origin-enzymes including CPK is recognized in cases of atypical pneumonia, it may be the clue of diagnosis of psittacosis. PMID- 2243195 TI - [Type-specific antibody to type Ia, Ib, II and III group B Streptococcus in maternal and neonatal sera measured by ELISA]. AB - In order to determine the type-specific antibody to group B streptococcus (GBA) type Ia, Ib, II and III, the ELISA system was established in Research laboratories, Toyo Jozo Co., Ltd. We assayed type-specific antibody by this ELISA system in both maternal and neonatal (or cord) sera. The cut off levels were determined by the antibody levels of maternal and neonatal sera of 26 infected cases and 90 GBS carriers, that type Ia, Ib, II were 0.20 and type III was 0.15. Prevalence of type-specific antibody levels were studied in 356 maternal sera (14 affected cases, 100 GBS carriers and 242 non carriers). Antibody levels were positive in 47.2% of maternal sera to type Ia, 34.0% to type Ib, 46.9% to type II and 45.5% to type III. Antibody levels to type Ia, Ib, II and III were positive, respectively, in 100%, 88.2%, 25.0% and 42.9% of the sera of carrier mothers whose infants were not affected. Antibody levels in 50 pair sera of maternal and cord blood were well correlated. PMID- 2243197 TI - [Biological significance of alternative translation]. PMID- 2243198 TI - [Anabolic roles of peroxisomes]. PMID- 2243199 TI - [Ganglioside as a potential immune modulator: selective CD4-modulation and inhibition of human immunodeficiency virus infection]. PMID- 2243200 TI - [Adult T-cell leukemia derived factor/human thioredoxin (ADF/hTx)]. PMID- 2243201 TI - Lesions of the petrous apex. AB - While lesions of the petrous apex are uncommon, they may present significant morbidity to the patient. The symptoms elicited by these lesions are usually vague and nonlocalizing in the early stages but progress to include multiple cranial neuropathies. Early diagnosis requires a high index of suspicion and use of appropriate imaging modalities. Thorough preoperative assessment with use of CT, MRI, and carotid arteriography is essential to plan the optimal surgical approach. Previously considered inaccessible, technical advances in skull base surgery have made this region more approachable. PMID- 2243202 TI - Psychiatry in the 1990s. PMID- 2243203 TI - Obsessive compulsive patients: familial frustration and criticism. AB - Familial factors such as attitudes toward illness, knowledge of disease process, and criticism of patients often play an important role in patient compliance and outcome in general medical practice as well as in psychiatric settings. As part of the initial assessment in a psychoeducational group for obsessive compulsive disorder patients and their significant others, nonpatients completed the Relative's Reactions Questionnaire and the Control of Symptoms Schedule. The patients completed the Perceived Criticism Measure. Results suggest that significant others experience frustration with the symptomatic behavior of their friend or family member with obsessive compulsive disorder and may respond too frequently with verbal criticism. The patients themselves reported a moderately high level of criticism from significant others at home. Further research is needed on a larger sample size and with nonpsychiatric and nonobsessive compulsive disorder psychiatric controls. PMID- 2243204 TI - Psychiatric disorders in the medically ill. AB - Psychiatric disorders commonly coexist in patients with medical illness. Three disorders encountered frequently are anxiety disorders, depression, and delirium. The authors discuss these psychiatric disorders and their treatment in medically ill patients. Psychiatric consultation may be helpful in such cases. PMID- 2243205 TI - Premenstrual syndromes. AB - Premenstrual Syndrome and Late Luteal Phase Dysphoric Disorder are two commonly cited premenstrual syndromes. Some of the problems in research include prospective vs retrospective rating scales, lack of confirmation of treatment response by double-blind studies, and a large placebo response. Treatment is still largely empiric. Many patients who present with premenstrual complaints may benefit from psychiatric referral. PMID- 2243206 TI - Reflections on malpractice liability. PMID- 2243207 TI - ECG of the month. Horns of a dilemma. Normal electrocardiogram. PMID- 2243209 TI - Radiographic demarcation of the acetabular bone-cement interface. The effect of femoral head size. AB - Between 1983 and 1988, 182 total hip arthroplasties were inserted using modern cement techniques including metal-backed acetabular components. Femoral head size was 32 mm in 84, 22 mm in 98. Radiographic analysis revealed three-zone demarcation of acetabular bone-cement interface in 56% of the 32 mm group as compared to 5% of the 22 mm group at 19 and 24 months mean follow-up period, respectively. When a subgroup of women under 60 years of age was created to control variables, the high-grade demarcation rates were 67% and 18%, respectively. Although Charnley hip scores remain similar between the two groups, these results emphasize the adverse effects of large femoral head prostheses on cement-bone interface and underline the need for alternative methods of fixation. PMID- 2243208 TI - Rapid recovery in mice after combined nasal/oral immunization with killed respiratory syncytial virus. AB - Based on the concept of a common mucosal immune system, the murine gastrointestinal tract was inoculated (oral) with three doses (5, 20, and 40 micrograms) of UV-inactivated respiratory syncytial virus (RSV) in order to elicit a virus-specific immune response in the respiratory tract. Only the 40 micrograms dose induced significant (P less than 0.01) anti-RSV-IgG rises in serum and lung wash compared to controls. To improve the immune response, mice were immunized intranasally under light anesthesia with the same 40 micrograms dosage regimen of killed RSV so that each dose passed through the nose and was swallowed. This combined nasal/oral immunization stimulated anti-RSV-IgG in serum, lung wash and nasal wash (P less than 0.001) and anti-RSV-IgA in lung and nasal wash (P less than 0.001) that were comparable to levels after infection with live RSV. Three days after challenge with live RSV, mice given combined nasal/oral immunization showed suppressed nasal virus shedding (P = 0.025). Nasal virus shedding correlated inversely with concentrations of anti-RSV-Ig in nasal secretions but did not correlate with concentrations in serum. PMID- 2243210 TI - Tc-99m-MDP scintigraphy not informative in painful total hip arthroplasty. AB - In 61 painful cemented total hip arthroplasties the diagnostic specificity was 0.7 for plain radiography and 0.46 for scintigraphy. The diagnostic sensitivity was 0.97 for radiography and 0.77 for scintigraphy. False negative radiology occurred in 0.05 and false positive in 0.23. False negative scintigraphy was encountered in 0.27 and false positive in 0.49. Seven of thirty-nine hips were operatively explored because of false positive scintigraphy. In conclusion, Tc 99m-MDP scintigraphy could not used as a complementary diagnostic measure in our hands. PMID- 2243211 TI - An analysis of screw fixation of the femoral component in cementless hip arthroplasty. AB - A cementless hip stem that allows screw fixation of the collar to cortical bone in the calcar region was found to achieve enhanced rotational stability when implanted in preserved cadaveric human femora. Although the implants with screws showed less tendency for subsidence than the implants without screws, rotational micromotion was not found to be statistically different under light loading conditions. When implanted in composite bone, the addition of screws in the configuration tested was associated with significant metal-on-metal wear during combined compression and rotational cyclic loading. This finding is of concern due to potential wear particle toxicity and possible lowered fatigue life of the prosthesis. Therefore, specific design changes are recommended. PMID- 2243212 TI - A comparative study of closed-wound suction drainage vs. no drainage in total hip arthroplasty. AB - One hundred consecutive primary total hip arthroplasties performed by the same surgeon over 4 years were retrospectively reviewed. In the first 50, closed suction drains were used; the following 50 were not drained. Comparison between the two groups revealed no statistically significant differences in wound problems, postoperative pyrexias, or other short-term complications. No wound infections occurred. A mean of 2.6 units of blood per patient was transfused to the nondrained group. In the drained group, a mean of 3.4 units of blood per patient was transfused. This difference was not statistically significant. The mean postoperative fall in haemoglobin concentration was 2.4 g/dl in the nondrained group, and 1.9 g/dl in the drained group. This difference was not statistically significant. This study demonstrated no advantage to the use of suction drains in uncomplicated total hip arthroplasty, and perhaps their routine use should be questioned. PMID- 2243213 TI - Allograft-implant composite reconstruction following periacetabular sarcoma resection. AB - Ten patients with primary periacetabular sarcomas were treated with internal hemipelvectomy and allograft-implant composite reconstruction. Three patients developed local recurrences, one of which was salvaged with repeat resection. One patient underwent hemipelvectomy for infected wound recurrence. At a mean follow up period of 25 months (range, 7-85 months; median, 18 months), six of nine patients assessed with the Musculoskeletal Tumor Society functional assessment had satisfactory results, with scores of 21 or better (of a possible 35). Although complications were frequent and functional scores were often limited by the muscle resection required for adequate tumor removal, we remain cautiously optimistic about the early results of this procedure. PMID- 2243214 TI - Interlocking femoral components for revision arthroplasty with allografts. AB - The use of interlocking screws has been advocated to fix major proximal femoral allografts to femoral prostheses. This study examines the effect of interlocking screws on strength of the component. Model femoral components were tested in axial compression. Drilling one hole diagonally (lateral to medial), drilling one hole anterior to posterior, or drilling one diagonal hole plus one anterior-to posterior hole did not significantly decrease failure load compared to controls with no holes. However, two diagonal holes or horizontal, medial-to-lateral holes were weaker. Four cases have been done with proximal femoral allografts fixed to porous-coated femoral components with proximal and distal interlocking screws. Initial results in these cases are good. PMID- 2243216 TI - The effect of retention of the femoral neck and of cement upon the stability of a proximal femoral prosthesis. AB - Radiological measurements of downward femoral component migration are reported for 203 hips in the first 2 years following total hip arthroplasty. The femora differed with respect to the retention of the femoral neck--in 167 it was retained and in 36 it was damaged--and to the use of cement--142 hips were press fits and 61 were cemented. Multivariate analysis demonstrated that both retention of the neck and the use of cement retarded migration (ie, increased stability) of the femoral component (P = .0003 and .0037, respectively). PMID- 2243215 TI - Revision of aggressive granulomatous lesions in hip arthroplasty. AB - Fourteen patients had revision arthroplasty for aggressive granulomatosis in 16 previously replaced cemented total hips. The revision was performed on average 8 years (range, 6-13 years) after the primary arthroplasty. Twelve patients had multifocal granulomatous lesions. Pain was the first clinical sign of the aggressive granulomatosis, beginning on average 1.7 years (range, 0.8-3.8 years) after the primary operation. One patient had a fracture of the femur due to large granulomas while waiting for revision. The patients were under follow-up evaluation for an average of 5.4 years (range, 4-7 years) after revision. Two patients had recurrence of aggressive granulomatosis at the original sites 4.5 and 6.5 years after revision. Eleven patients had good or excellent results of revision. PMID- 2243217 TI - Injury to the external iliac artery during hip arthroplasty for old central dislocation. AB - Injury to a major vessel is an uncommon but well recognized and serious complication of total hip arthroplasty. An increased risk of such injury has been reported in rheumatoid patients, in revision surgery, and with the injudicious use of particular instruments, especially the sharp Hohmann retractor. The authors report the case of a patient who sustained a laceration to his external iliac artery during the course of a hip arthroplasty for osteoarthritis secondary to old central dislocation. The cause of the injury is discussed and the relevant literature reviewed. PMID- 2243218 TI - A posterior approach to the hip joint with complete posterior capsular and muscular repair. AB - A posterior approach to the hip is described, which preserves the posterior hip capsule and short external rotators. These structures are reflected during exposure and are securely repaired to bone as a single capsulomuscular flap during wound closure. This approach has been used exclusively since December 1986 for uncomplicated primary hip arthroplasty. In 259 consecutive cases, there have been only two dislocations, both associated with significant trauma. PMID- 2243219 TI - The effect of a metal-back without a stem upon the fixation of a tibial prosthesis. AB - Three methods of tibial component fixation without cement (as part of TKA) have been used at the London Hospital. All three methods have used the same polyethylene component fixed with two HDP (Day) pegs. A metal-back without a stem was added to the HDP in group 1. Group 2 consisted of an HDP-only component. In group 3 a stem was added to the metal-back used in group 1. Radiological comparison showed the fixation of the polyethylene component with metal back but no stem to be inadequate; the component tilted into varus more frequently than the other configurations. It is suggested that failure was due to the increased rigidity of the metal-backed component (as compared with the HDP only) and that the rigidity (and the resultant tendency to rock) can be offset by a stem. It is concluded that rigid (ie, metallic) tibial components should have a stem. PMID- 2243220 TI - Revision surgery for stiff total knee arthroplasty. AB - Thirteen stiff total knee arthroplasties were studied in 12 patients who did not have a stiff knee prior to the index arthroplasty. The reasons for replacement were osteoarthritis in seven knees, post-traumatic arthritis in two, and inflammatory collagen disease in four. Four knees were revised for fixed flexion deformity and nine for poor arc of motion. The cause of stiffness in eight knees was malpositioned components. Following postoperative revision for stiffness, three knees received excellent ratings, two received good ratings, four received fair ratings, and four received poor ratings. Satisfaction was achieved in 11 of 12 patients because of pain relief. Improved motion was achieved in patients with primary osteoarthritis and patients with malposition of components. Poor motion occurred in those with patella baja and inflammatory collagen disease. A V-Y patella turndown helped prevent patella ligament complications. PMID- 2243221 TI - Revision of a loose glenoid component facilitated by a modular humeral component. A technical note. AB - Revision of a glenoid component can be difficult in the presence of a humeral component. Removal of the humeral component is generally required, which adds significantly to the difficulty of the procedure and increases the risk of complications. This report describes revision of a loose glenoid component that was greatly facilitated by the presence of a modular humeral component. PMID- 2243222 TI - Capitello-Condylar total elbow arthroplasty for rheumatoid arthritis. AB - Twenty-one total elbow arthroplasties using the Capitello-Condylar design of Ewald were performed at the Denver Orthopedic Clinic from 1977 to 1986. Indications for operation included intractable pain unrelieved by medical therapy as well as late state III or IV rheumatoid arthritis. The average total elbow score at 48 months after operation was 89.5 points, including excellent pain and function ratings. Modest gains in motion occurred with lesser gains in patients with juvenile rheumatoid arthritis than those of the adult variety. Forty percent of the elbows suffered some type of complication although most are successfully manageable. There was one clinical failure due to deep infection in a renal deficient patient. PMID- 2243224 TI - The spontaneous spinal epidural hematoma. A study of the etiology. AB - From the literature 199 cases of spontaneous spinal epidural hematoma (SSEH) are analyzed. With these data and the vascular anatomical characteristics of the spinal epidural space, the theories on the etiology of the SSEH are discussed. There seems to be no relationship between the SSEH and arterial hypertension. The age highly affects the level-distribution of the SSEH. The authors have the opinion that the posterior internal vertebral venous plexus plays an important part in the etiology of the SSEH. In the literature the role of a vascular anomaly in the etiology of the SSEH is overestimated. The cluster-type dural artery can easily be mistaken for a vascular anomaly. PMID- 2243223 TI - Utilization and effectiveness of autologous blood donation for arthroplastic surgery. AB - Autologous blood predeposit before elective surgery is a rapidly expanding transfusion practice. The authors have conducted a 3-year analysis of an autologous blood predeposit program to assess its impact on orthopaedic joint surgery. The authors conclude: autologous blood donation has resulted in a reduction of homologous blood transfusions in patients undergoing elective hip and knee procedures from 73% to 18% and from 71% to 12%, respectively. In addition, autologous blood preoperative donation in elective orthopaedic joint surgery has increased dramatically, so that while previously this practice was considered underutilized, autologous blood as an alternative to homologous blood transfusion now represents a standard of practice for elective orthopaedic joint arthroplasty at University Hospitals of Cleveland. PMID- 2243225 TI - Proteolytic enzyme activities during regeneration of the rat gastrocnemius muscle. AB - The enzymatic activity of creatine phosphokinase and the lysosomal enzymes cathepsin D and acid phosphatase was followed during skeletal muscle regeneration after partial excision to the gastrocnemius muscle in the rat. For each time interval (1, 2, 5, 14 and 45 days) following injury, the activity of the regenerated muscle was compared with the activity in the contralateral sham operated muscle. The specific activity of creatine phosphokinase of the regenerated muscle showed a significant decrease (25%) during the first 2 days post injury and thereafter was comparable to that of the uninjured control muscle. The activity of cathepsin D was 2.3-4-fold significantly higher in the regenerated muscle than in the control intact muscle from day 1 until day 14 post injury. At 45 days after partial excision, the activity of this enzyme was comparable to a normal muscle. However, the activity of another lysosomal enzyme (acid phosphatase) did not show any distinct changes from the level of this enzyme in the uninjured muscle during the course of muscle regeneration. It is suggested that elevation of lysosomal enzymes in skeletal muscle may not be confined to conditions of muscle wasting and degradation but also to differentiation and development processes such as during muscle regeneration following injury. PMID- 2243227 TI - Aneurysms and vacuolar degeneration of cerebral arteries in late-onset acid maltase deficiency. AB - We present a case of late-onset acid maltase deficiency (AMD) with pronounced involvement of the liver and skeletal muscles. In addition, and in contrast to other adult cases of AMD, the case presented here shows CNS pathology with hypodense and hyperintense white matter areas on CT and MRI scans, and myelin changes ranging from focal areas of demyelination to necrosis. Neuropathologic changes seem to be related to unusual vascular pathology consisting of vacuolar degeneration of small and large arterial blood vessels. Vacuoles of varying size, partly filled with granular PAS-positive material, were found in pericytes and smooth muscle cells of arterial vessel walls. Electron microscopy revealed lysosomal and cytoplasmic free glycogen in smooth muscle cells in the intima of large cerebral arteries as well as in pericytes of arterioles and capillaries. Accumulation of glycogen locally was associated with severe cellular damage and necrosis. The formation of a great number of small aneurysms of intracerebral arteries is thought to be the result of cell damage in the vessel walls. PMID- 2243226 TI - Degradation of connectin (titin) in Fukuyama type congenital muscular dystrophy: immunochemical study with monoclonal antibodies. AB - Connectin (also called titin) is a myofibrillar elastic filament which links a thick filament to a neighbouring Z line in a sarcomere and thus contributes significantly to the elasticity of myofibrils. In a previous study, we demonstrated by Western blot analysis of the biopsied skeletal muscles using an anti-connectin monoclonal antibody that connectin was degraded extensively after 5 years of age in Duchenne muscular dystrophy (DMD), while it was degraded mildly in Becker muscular dystrophy and only minimally in myotonic dystrophy, limb girdle dystrophy, amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. In the present study, we investigated the degradation state of connectin in Fukuyama type congenital muscular dystrophy (FCMD) by a similar method using 2 distinct anti-connectin monoclonal antibodies. In FCMD, connectin degradation began much earlier than in DMD: Definite degradation was already observed in 5-8 month-old patients. It was presumed that connectin degradation would play an important role in the myofibrillar degeneration in the early stage of FCMD. PMID- 2243228 TI - Antimitochondrial autoantibodies of primary biliary cirrhosis as a novel probe in the study of 2-oxo acid dehydrogenases in patients with mitochondrial myopathies. AB - Autoantibodies present in the autoimmune disease primary biliary cirrhosis react by immunoblotting with four human skeletal muscle mitochondrial antigens of 70 kDa, 52 kDa, 50 kDa and 45 kDa, identified as the lipoate acetyl transferases (E2) of the pyruvate dehydrogenase, component X of E2 pyruvate dehydrogenase, E2 of 2-oxo glutarate dehydrogenase and E2 of branched-chain 2-oxo acid dehydrogenase complexes respectively. These autoantibodies have been employed as a novel probe to study whether there is a defect in the synthesis of the 2-oxo acid dehydrogenase complexes in patients with mitochondrial respiratory chain disorders. The reactive antigens are present normally in four patients with oculomyopathy in whom partial deletions of the mtDNA have been detected, and in two patients with MERRF and MELAS encephalomyopathy. Thus, unlike in the yeast Saccharomyces cerevisiae, there appear to be no regulatory interactions which coordinate the assembly of the mitochondrial respiratory chain with the development of the pyruvate dehydrogenase complex, which plays an important role in regulating the flow of metabolic intermediates to oxidative energy metabolism. PMID- 2243229 TI - Emotional facial paresis with striatocapsular infarction. AB - Emotional facial paresis (EFP) refers to hemifacial paresis of emotionally evoked or spontaneous smiling or weeping with preserved volitional movements of the face. The anatomical location for this phenomenon has been controversial. We report a 15-year-old boy with EFP. Follow-up MRI demonstrated infarction limited to the head of the caudate, putamen and anterior limb of the internal capsule on the contralateral side. This case lends support for selective damage at a striatal or capsular site in the production of EFP. PMID- 2243230 TI - Prognosis of asymptomatic carotid occlusion. AB - Ninety-four asymptomatic patients with internal carotid artery occlusion were followed for a mean of 44 months, 16% suffered strokes and 11.7% reported transient ischemic attacks (TIA). The annual stroke and TIA rates were 4.4% and 3.2%, respectively, the annual mortality was 11.3%. In 27 asymptomatic patients progression of extracranial arterial disease to occlusion was observed: 7.4% of these patients suffered from stroke and 18.5% reported TIA's during that period. Thus the annual stroke rate was lower (1.9%) but the TIA rate higher (4.7%) than post-occlusive rates. These data reflect an increase risk in patients with progressive high-degree carotid stenosis which continues after occlusion. This may favour carotid endarterectomy for selected patients in the pre-occlusive state because medical treatment has not been shown to prevent progression of stenosis to occlusion. PMID- 2243231 TI - Hormonal changes in cerebral infarction in the young and elderly. AB - Fifty-one patients with CCT verified cerebral infarction were submitted to serum and CSF radioimmunoassay of FSH, LH, estradiol (E2), progesterone, testosterone, cortisol and T4. The results were compared to those of 82 matched controls. Our findings suggest that (1) high serum E2 is a risk factor of stroke in males; (2) low serum T4 is a risk factor in males; (3) serum testosterone is reduced in acute stroke in males confirming that it is stress sensitive; (4) serum LH was higher in hypertensive thrombotic males when compared to normotensive ones, and (5) FSH, LH, E2 and T4 are undetectable in CSF of patients and controls. PMID- 2243232 TI - Tangier disease: central nervous system impairment in a case of syringomyelia like syndrome. AB - A neuroradiological investigation of the central nervous system (CNS) in a case of Tangier disease presenting as a syringomyelia-like syndrome is reported. No syringomyelinic cavities were found. However, MRI showed cervical spinal cord atrophy and scattered foci of greater density with T2 weighted images in the white matter of the frontal, parietal and occipital lobes. Cerebral and cervical spinal cord involvement in the course of Tangier disease is now shown for the first time. The authors postulate that the MRI detected alterations are related to the underlying illness. PMID- 2243233 TI - Determination of manganese concentrations in the spinal cords from amyotrophic lateral sclerosis patients by inductively coupled plasma emission spectroscopy. AB - Continuing analytical studies on environmental factors in the foci of amyotrophic lateral sclerosis (ALS) in the Kii Peninsula of Japan and Guam, and metal analysis using neutron activation analysis in central nervous system (CNS) tissues from ALS cases indicate that chronic exposure to metals such as aluminum and manganese, together with a deficiency of minerals such as calcium and magnesium, may play a causative role in the neurodegeneration seen in ALS. An accurate and simple method for detecting minerals and trace metals in small, fresh samples of CNS tissue is necessary in order to follow the pathogenetic behavior of these elements. In this paper, we describe a method for measuring manganese (Mn) content in CNS tissue samples taken from mouse brain using inductively coupled plasma (ICP) spectroscopy and present results of the determination of Mn contents in spinal cord samples from ALS cases using the same method. ICP emission spectroscopy is considered to have great advantage for the simultaneous determination of elements in small, fresh CNS samples because of its simplicity and convenience, and the elimination of the necessity to use potentially dangerous acids. Results showed that the mean concentration of Mn in a mouse brain (0.56 microgram/g) and in human spinal cords (0.39 microgram/g wet weight in the anterior horn, 0.37 in the lateral fasciculus, 0.39 in the posterior horn and 0.28 in the posterior fasciculus) were compatible with results previously reported using other methods. In ALS spinal cords, the mean content of Mn was similar to that of controls, but the distribution differed. In the ALS cases, Mn contents were higher in the anterior horn and lateral fasciculus than in the posterior horn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243234 TI - Congenital cerebellar hypoplasia and hypogonadotropic hypogonadism. AB - The association of cerebellar ataxia and non-neurological syndromes is a well known phenomenon. A 20-year-old male patient presented with a longstanding and non-progressive ataxia. Magnetic resonance examination revealed marked inferior vermian-cerebellar hypoplasia. He also showed a hypogonadism with low serum gonadotropin and prolactin levels. Chronic pulsatile gonadotropin-releasing hormone (GnRH) administration resulted in a small non-pulsatile luteinizing hormone (LH) increase and no follicle-stimulating hormone (FSH) elevation. This hormonal pattern suggests a primary deficiency of the gonadotroph and lactotroph cells, rather than a hypothalamic lesion. This is the first report where cerebellar hypoplasia of congenital origin is associated with hypogonadotropic hypogonadism. Because of consanguinity, autosomal recessive transmission is considered. PMID- 2243235 TI - Mast cells in neuromuscular diseases. AB - The lectin Dolichos biflorus agglutinin has been used to identify mast cells in normal skeletal muscle and to investigate changes in their number in a wide range of human neuromuscular diseases and in rat muscle damaged by the local anaesthetic bupivacaine. Few mast cells were found in the perimysium of normal skeletal muscle but numbers were increased in human muscle biopsies which showed necrosis and regeneration of fibrosis. In bupivacaine-induced muscle damage, increased mast cell counts occurred during the necrotic phase and particularly during the phase of active regeneration. In addition, increased numbers of mast cells were observed in the underlying histologically normal muscle. These results show that mast cells are influenced by pathological changes in skeletal muscle and, in view of the known functions of mast cells in other tissues, it is possible that they are capable of modulating disease processes in muscle. PMID- 2243236 TI - Kinetics of production of a novel growth factor after peripheral nerve injury. AB - In response to transection injury, the distal segment of sciatic nerve produces a soluble factor which stimulates neurite outgrowth from 15 day embryonic rat dorsal root ganglion (DRG) neurons, and PC12 cells. This activity enhances survival of large sensory neurons, promotes myelination and has been designated SN. The expression of SN, undetectable in the perineurium and proximal segments, occurs solely in the endoneurium distal to the site of permanent transection. When the distal portion is removed immediately after transection, homogenized and the supernatant tested, there is little neurite promoting activity in the normal nerve. For the first 10 days after transection the major soluble factor present in the distal segment is NGF. The amount of neurite promoting activity increases after 10 days and appears to plateau at 30-35 days while the proportion that is inhibited by anti-NGF decreases. In a competitive receptor binding assay, SN does not compete with 125I-NGF for receptors on either DRG or PC12 cells. Separation using polyacrylamide-agarose followed by HPLC demonstrates that SN migrates with polypeptides of molecular weights 17.2 and 19.1 kDa. PMID- 2243237 TI - Enhanced CNS uptake of systemically administered proteins through conjugation with tetanus C-fragment. AB - No other exogenous protein enters the central nervous system from the circulation as readily as tetanus toxin. We examined the capability of the non-toxic binding fragment of tetanus toxin (C-Fragment) so serve as a vehicle for transport of other proteins into the mouse CNS. Using periodate oxidation of the enzyme horseradish peroxidase (HRP), we synthesized two separate macromolecular complexes, one containing C-fragment and HRP, and the other C-fragment, HRP and a third "test" protein-human IgG. The distribution of C-fragment-HRP was typical of blood borne proteins including native C-fragment, with labeling of all neurons with known projections outside the blood-brain barrier, particularly large spinal motoneurons. C-fragment-HRP conjugates showed superior neuronal labeling to over 100-fold greater quantities of free HRP. Complexes containing C-fragment, HRP and human IgG were internalized by neurons from both intramuscular and intraperitoneal injections. The efficiency of neuronal uptake of IgG in the C fragment conjugated form was enhanced over 40-fold compared to free IgG. Linkage of a large protein to C-fragment probably leads to enhanced endocytosis of that protein by neuronal terminals projecting outside the blood-brain barrier. C fragment can serve as a vehicle to allow selected proteins to bypass the barrier and enter the CNS. PMID- 2243238 TI - Ultrastructural abnormalities of myelinated fibres in the tibial nerve of streptozotocin-diabetic rats. AB - In this paper we have examined the ultrastructural changes in myelinated fibre structure after the administration of streptozotocin to Sprague-Dawley rats which had passed the rapid growth period. Myelinated fibre size in the tibial nerve was found to be less in diabetic animals 4 and 6 months after the induction of diabetes, when compared to age-matched controls, but not less than onset. The relative contributions of axon and myelin to this reduction in fibre dimensions were examined. When myelin area was plotted against axon area (derived from perimeter) it showed that the pathological insult of diabetes had a greater effect on the rate of myelin production. The incidence of axonal glycogenosomes was also assessed. These results are discussed in detail. PMID- 2243239 TI - Cocaine-induced stroke: first Jamaican case. PMID- 2243240 TI - An unbiased estimation of the total number of synapses in the superior cervical ganglion of adult rats established by the disector method. Lack of change after long-lasting sodium bromide administration. AB - Previous physiological and morphological studies suggested that sodium bromide promotes synaptogenesis of implanted cholinergic nerves in the superior cervical ganglion of adult rats. To check whether sodium bromide also modifies synaptic numbers in the intact ganglion, quantitative electron microscopy was used to determine the total number of synaptic junctions in the superior cervical ganglion of adult rats. Untreated controls were compared with animals which drank water containing 280 mg ml-1 sodium bromide for 7 days. The disector method, an unbiased estimator of volume density of certain particles, has been adapted to this particular case. To accomplish the task, an on-line counting procedure was developed, which permitted the efficient adaptation of the disector method for the superior cervical ganglion, in which the synapses are known to be distributed sparsely. Three pairs of (control and treated) ganglia have been completely processed by three independent examiners. The estimated number of synapses in the ganglia ranged from 4 to 8 million while the volumes of the ganglia varied from 0.65 to 0.90 mm3. Evaluation of the results showed that variations in the total number of synapses were in each case proportional to differences in ganglionic volumes. This suggests that: (1) sodium bromide does not lead to changes in density of intrinsic synapses; and (2) the morphogenetic action of sodium bromide on principal ganglion cells previously described is essentially postsynaptic and requires additional presynaptic elements to increase the number of synapses. PMID- 2243241 TI - Development of the ultrastructural features of neuropeptide Y-immunoreactive neurons in the rat visual cortex. AB - Immunohistochemical studies have localized neuropeptide Y into a small population of non-pyramidal neurons in the mammalian cerebral cortex. In the rat, these cells are distributed in layers II-VI and are characterized at the ultrastructural level by an abundance of cytoplasm containing a plethora or organelles, most conspicuous of which are cisternae of granular endoplasmic reticulum stacked in parallel arrays. In the present study, we used electron microscopic immunocytochemistry to examine the ultrastructural development of neuropeptide Y-labelled neurons in the rat visual cortex from birth, when they first appear in this cortical area, until postnatal day 32. At birth and in the subsequent few days, neuropeptide Y neurons, found exclusively in layers V and VI, often show a deeply infolded nucleus and little cytoplasm containing few organelles. At the end of the first postnatal week, labelled cells are still restricted to layers V and VI and display immature features. However, at this stage, cells often show irregularly enlarged proximal dendrites filled with organelles. During the second postnatal week, neuropeptide Y-immunoreactive cell bodies appear for the first time in layers II and III, and at the end of this week they have a distribution similar to that observed in the adult. Labelled cells are overall more differentiated than at earlier ages showing some of the ultrastructural features which distinguish them in the adult. No differences in maturation are evident between immunoreactive neurons located in the superficial layers and those in the deep layers, suggesting that the neuropeptide Y neurons in the more superficial layers express the peptide after having completed their migration and have acquired their characteristic ultrastructural features. Maturation proceeds during the third postnatal week. At the end of this stage, neuropeptide Y-containing cells acquired their mature nuclear and cytoplasmic features and an adult complement of synapses. PMID- 2243242 TI - Antigenic staining patterns of human glioma cultures: primary cultures, long-term cultures and cell lines. AB - The immunocytochemical staining patterns of cultured glioma cells were investigated. Fifty nine individual cases were stained at different in vitro ages for glial fibrillary acidic protein, fibronectin, galactocerebroside, HNK-1/Leu 7, A2B5, vimentin, factor VIII and A4. Histologically, the cases were composed of eight low-grade astrocytomas, 11 high-grade astrocytomas, four low-grade oligodendrogliomas, seven high-grade oligodendrogliomas and 29 glioblastomas. The 45 cases were analysed within the first 3 weeks of culture, many of them as primary cultures. In 11 cases stainings were performed repeatedly at intervals of up to 6 months. Glial fibrillary acidic protein staining was positive in most of the early cultures of astrocytomas (low and high grade) and glioblastomas; expression in more than 50% of the cells was found in 1 of 5 low-grade astrocytomas, 5 of 11 high-grade astrocytomas and 14 of 29 glioblastomas. Two of the high-grade astrocytomas were stained once more after 6 weeks in culture and were found to be only 1% positive for glial fibrillary acidic protein but strongly positive for fibronectin. The same was true for five of the glioblastoma cases. Two of these cases remained glial fibrillary acid protein positive and developed into stable permanent cell lines. Only one case started with 1% of glial fibrillary acidic protein positive cells and later developed into a 99% glial fibrillary acidic protein positive cell line. Neither HNK-1/Leu 7 expression nor A2B5 staining appeared to have a relationship to the glial fibrillary acidic protein staining. It was observed that glial fibrillary acidic protein and HNK-1/Leu 7 were both 100% in some cases but that later one of the two antigens disappeared but not the other. The amount of glial fibrillary acidic protein staining does not allow the prediction of A2B5 staining. The study shows that initiation of primary cultures on an extracellular matrix yields more glial fibrillary acidic protein positive cells in primary cultures than have been found in other studies. It is concluded that only a rigid standardization of culture conditions will ensure the validity of comparisons of in vitro data obtained in primary cultures. PMID- 2243243 TI - Identification of all GABA-immunoreactive neurons projecting to the lobster stomatogastric ganglion. AB - The stomatogastric ganglion of lobsters (Homarus or Jasus) contains a large number of gamma-aminobutyric acid-immunoreactive processes originating from ten fibres in the single input nerve, the stomatogastric nerve. The cell bodies and axonal pathways of these ten fibres have been identified using gamma-aminobutyric acid immunohistochemistry in combination with Lucifer Yellow staining (double labelling) and nickel chloride backfilling (selective gamma-aminobutyric acid immunoinhibition). It is shown that eight gamma-aminobutyric acid-immunoreactive neurons project to the stomatogastric ganglion: gamma-aminobutyric acid neurons 1 and 2, found posterior to the oesophageal ganglion, entering the stomatogastric nerve via the oesophageal nerve as well as sending an axonal branch into each superior oesophageal nerve; gamma-aminobutyric acid neurons 3 and 4, found anterior to the oesophageal ganglion, each sending an axonal branch into each inferior oesophageal nerve to reach the stomatogastric nerve via the commissural ganglion and the superior oesophageal nerve; and gamma-aminobutyric acid neurons 5 and 6, found in each commissural ganglion, projecting into the stomatogastric nerve via the inferior oesophageal nerve, the oesophageal ganglion and the oesophageal nerve. These gamma-aminobutyric acid-immunoreactive neurons were also characterized by electrophysiological methods coupled with Lucifer Yellow labelling, and their picrotoxin-sensitive effects on several stomatogastric ganglion neurons were demonstrated. The present results provide a firm basis for further studies concerning the physiological significance of one class of neurochemically-defined input neurons to stomatogastric ganglion networks. PMID- 2243244 TI - Serotonin-like immunoreactivity in the retina of the clawed frog Xenopus laevis. AB - Using an antiserum directed against serotonin, we have studied the morphology and distribution of serotonin-containing and serotonin-accumulating neurons in the retina of Xenopus laevis. Endogenous serotonin-like immunoreactivity was found in two classes of amacrine cell, one class of bipolar cell and a few centrifugal fibres. Kainic acid-induced depletion of serotonin, under various conditions, enabled us to determine the distribution of stained bipolars, amacrine cells and centrifugal fibres within the meshwork of serotonin-like immunoreactivity labelled processes. Kainic acid-induced release of serotonin by bipolar cells is calcium dependent. Stimulation of release by kainic acid as well as the fact that all serotonin-like immunoreactive bipolar cells ramify in sublayer 1 of the inner plexiform layer suggest that serotonergic bipolars are OFF centre cells. Release of serotonin from amacrine cells is largely calcium independent. Serotonin containing amacrines send primary dendrites into layer 1 of the inner plexiform layer; short off-shoots from the primary dendrites descend into sublayers 3-5 in which they ramify into a fine network. Serotonergic amacrines have an uneven distribution in the Xenopus retina. Their highest density occurs in the posterolateral quadrant, whereas large portions of the anteromedial quadrant lack serotonin-like immunoreactivity altogether. The uneven distribution of serotonin containing elements in the Xenopus retina with its peak falling onto the retinal area which generates binocular vision, suggests its involvement in binocular perception. PMID- 2243245 TI - Structure, distribution and number of surface sensilla and their receptor cells on the olfactory appendage of the male moth Manduca sexta. AB - Distribution and neuronal organization of sensilla on the surface of the annulate flagellar segment of the antenna of the male Manduca sexta were studied by scanning and transmission electron microscopy. Nine types of sensilla were identified and their bipolar neurons ascribed to specific sensory modalities on the basis of their cuticular and dendritic morphology. Cuticle morphology identifies two types of sensilla trichodea, two types of sensilla basiconica and one type of sensillum coeloconicum. Certain of these olfactory sensilla are further subdivided on the basis of their dendritic structures. One type of sensillum chaeticum was interpreted as a contact chemoreceptor. A second type of sensillum coeloconicum and a styliform sensilla complex were interpreted as bimodal hygro- and thermosensilla. A second species of sensillum chaeticum serves mechanosensation. Counts from annuli situated about midway along the flagellum revealed a total of about 2200 sensilla supplied by approximately 5160 sensory neurons. A conservative estimate suggests that a male antenna with 85-90 annuli provides the flagellar nerve with at least 3.6 x 10(5) receptor axons, a number that exceeds previous estimates by almost 50% Each species of receptor has a characteristic location on the annulus. Of the 2100 or so sensilla situated on the dorsal, ventral and the leading edge surfaces, about 800 consist of male specific type-I trichoids containing pheromone-sensitive receptors. Arciform arrays of these sensilla on the upper and lower surfaces of each annulus presumably optimize the capture and absorption of odour molecules. The trailing edge of the flagellum, which is thickly covered by scales and was assumed until now to lack receptors, contains both mechanosensitive and contact chemoreceptors. The modality of non-olfactory receptors is considered with respect to similar elements that have been functionally identified in other species. The coexistence of non-olfactory sensilla with olfactory elements is discussed with respect to current knowledge of the organization of olfactory centres in the brain. PMID- 2243246 TI - Ultrastructure and synaptology of neurons immunoreactive for gamma-aminobutyric acid in the myenteric plexus of the guinea pig small intestine. AB - Immunoreactivity for gamma-aminobutyric acid is located in one morphologically defined class of nerve cell body in the myenteric plexus of the guinea pig small intestine. These are a subgroup of the Dogiel type I nerve cells, characterized by their lamellar dendrites, about 1 micron thick and flattened in the plane of the myenteric plexus, and one (or rarely two) long axonal process that extends to either the longitudinal or the circular muscle. At an ultrastructural level the dendrites were characterized by their open cytoplasm in which were scattered granular vesicles, pale mitochondria, Golgi apparatus and endoplasmic reticulum. A large proportion of the dendritic surface was in direct contact with the extra ganglionic space. In the cell body region, which was away from the ganglion surface, the nucleus was surrounded by a thin rim of cytoplasm. The cytoplasmic features are quite distinct from those of Dogiel type II neurons but they were shared by many other non-immunoreactive neurons. Synaptic inputs, which were all non-immunoreactive, were found on the dendrites, cell bodies, axon hillocks and axons of the gamma-aminobutyric acid-immunoreactive neurons. The predominant vesicle type in the presynaptic elements was the small clear vesicle, 40-60 nm in diameter. Based on two gamma-aminobutyric acid-immunoreactive cells that were examined in serial section, about 40-50% of synapses are dendritic, 20-25% are somatic, and 30-35% are on the axon hillock or first 50-70 microns of the axon. No synapses formed by immunoreactive varicosities were found on non immunoreactive neurons or in the neuropil of the myenteric ganglia. Moreover, the lamellar dendrites or soma of gamma-aminobutyric acid neurons were never presynaptic elements forming relationships with other elements in the ganglia. It is concluded that the gamma-aminobutyric acid reactive Dogiel type I neurons are motor neurons providing inputs to the circular and longitudinal muscle layers. PMID- 2243247 TI - Highly sialylated N-CAM is expressed in adult mouse optic nerve and retina. AB - The localization of the neural cell adhesion molecule (N-CAM) and its highly sialylated form, which is prevalent in young tissues and has therefore been called embryonic neural cell adhesion molecule, was studied in the developing and adult mouse optic nerve and retina immunohistologically and immunochemically. At embryonic and early postnatal ages, neuroblasts and young postmitotic neurons, Muller cells and astrocytes in the retina, and retinal ganglion cell axons and all glial cells in the optic nerve express highly sialylated neural cell adhesion molecule. Beginning with the third postnatal week, highly sialylated neural cell adhesion molecule disappears from retinal ganglion cell axons in the optic nerve and from neuronal cell bodies and processes in the retina. In addition, it is not detectable on oligodendrocytes in 3-week-old animals. However, highly sialylated neural cell adhesion molecule continues to be expressed in the adult optic nerve and retina by astrocytes and Muller cells. On these cells it is only absent from cell membranes contacting basal lamina. Weakly sialylated neural cell adhesion molecule, in contrast, is expressed by all cell types of retinal and optic nerve during development and in the adult. The loss of highly sialylated neural cell adhesion molecule from neurons and oligodendrocytes must therefore be considered as a cell type-specific conversion of the so-called embryonic to the adult form of neural cell adhesion molecule and does not simply reflect the disappearance of neural cell adhesion molecule from these cells. Weakly sialylated neural cell adhesion molecule, however, is absent from outer segments of photoreceptor cells and, as is the case for the highly sialylated form, from glial cell surfaces contacting basal lamina. Thus, the expression of highly sialylated neural cell adhesion molecule by pre- and postmitotic neurons and by oligodendrocytes is restricted mainly to the period of histogenetic events in retina and optic nerve, i.e. cell division, cell migration, dendritic and axonal growth and synaptogenesis. In addition to the observation that this form of neural cell adhesion molecule is less adhesive than the weakly sialylated, adult form, it is likely that highly sialylated neural cell adhesion molecule plays an important role during dynamic morphogenetic events. Furthermore, the expression of highly sialylated neural cell adhesion molecule by astrocytes and Muller cells in adult optic nerves and retinae suggests some histogenetically plastic functions for these cells in the adult mouse visual system. PMID- 2243248 TI - Effects of colchicine on central and peripheral nerve terminals of the locust Schistocerca gregaria. AB - The treatment of locusts (Schistocerca gregaria) with colchicine leads to various changes in the ultrastructure of both central and peripheral nerve terminals. These changes include a marked reduction in synaptic vesicle density, which is further enhanced following stimulation. There are also increased numbers of coated pits and membraneous cisternae together with enlarged terminal areas and disruption of mitochondrial ultrastructure. The capacity of isolated central nerve terminals (synaptosomes) to take up the radiolabelled transmitter precursor [3H]-choline is enhanced following in vivo treatment of locusts with colchicine, whilst in vitro treatment leads to a reduction in choline uptake. The results are discussed with regard to the postulated effects of colchicine on axoplasmic transport. PMID- 2243249 TI - Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. II. Synaptic junctions. AB - Four different types of axon terminals form symmetric synapses with the cell bodies and initial axon segments of pyramidal cells in layer II/III of rat visual cortex. One type belongs to chandelier cells, and the other three kinds of terminals have origins that have not been established yet. These latter are referred to as large, medium-sized and dense terminals. The purpose of the present study was to examine the synaptic junctions formed by all four types of terminal. The synapses formed by the chandelier cell terminals are readily recognized in thin sections because of the characteristics features of both the terminals and the initial axon segments, which are the neuronal elements postsynaptic to them. In en face views of these axo-axonal synapses the junctions can be seen to have presynaptic dense projections that form a grid in which they are triagonally spaced, and have an average centre-to-centre spacing of 84 nm. As an ensemble the projections form the presynaptic grid, which usually has an oval or round outline, but may be notched on one side where projections are absent. The synaptic junctions of the large, medium-sized and dense terminals were examined by making reconstructions of the terminals from serial thin sections. It was found that at the interfaces between the axon terminals and the cell bodies of pyramidal cells, several separate synaptic junctions may be present, in addition to a number of puncta adhaerentia. Thus, there may be as many as five separate synaptic junctions and as few as one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243251 TI - Chronic illness and depressive symptoms in the elderly: a population-based study. AB - A cross-sectional study of the distribution of depressive symptoms and association between depressed mood and chronic illness was conducted in a geographically defined population in southern California of 1617 men and women aged 65 years and older. The prevalence of depressed mood for the total population was 5.2%. Women exhibited a significantly higher mean depressive symptom score and a prevalence rate almost twice that of men. Depressive symptoms were associated with several risk factors in both sexes, including age, self perception of current health status, number of reported chronic diseases and medications and amount of exercise. However, the relationship between physical illness and depressive symptoms appeared to differ by sex with respect to the nature of the disease or disability and the type of medication currently used. These findings indicate that the risk of depression does not diminish with age among the elderly as other studies have suggested. PMID- 2243250 TI - The validity of single-item, self-assessment questions as measures of adult physical activity. AB - Individual energy expenditure (kcal/kg/day) was calculated from a detailed set of questions from the Health Promotion and Disease Prevention Supplement of the 1985 National Health Interview Survey. Responses to three single-item, self-assessment questions were compared to the energy expenditure variable to test criterion validity. Spearman's correlation coefficient revealed moderate correlations between energy expenditure and corresponding levels of self-assessed leisure-time physical activity for each single-item question (r = 0.14 to 0.41). For purposes of measuring prevalence of physical activity, the energy expenditure variable was used to categorize individuals into activity levels. The single-item questions were found to have Spearman's correlations with the categorical measures ranging from 0.11 to 0.37 for leisure-time activities. Generally higher correlations were found for males and younger age groups (18-34 years). The relationships were interpreted as being weak relative to an expected correlation of 0.75 for criterion validation. However, the single-item questions show promise for obtaining proxy estimates of the degree of leisure-time physical activity in a population. PMID- 2243252 TI - The relation between the plasma lipoprotein pattern and the waist/hip ratio in non-diabetic individuals. AB - Relations between lipoprotein indices and the waist/hip ratio (WHR) were examined in normoglycemic subjects (124 women and 63 men). Among women, an atherogenic lipoprotein pattern was strongly associated with WHR. The relation was greater than that of the lipoprotein pattern with either the body mass index or the subscapular/triceps ratio, and was independent of these adiposity measures. The association between low-density-lipoprotein cholesterol (LDL-cholesterol) and WHR was much stronger in thinner women than in those more obese (r = 0.64 vs r = 0.22, p = 0.001 for difference). Men had a more atherogenic lipoprotein pattern than women; however, with allowances for WHR the lipoprotein patterns were similar. These findings suggest that: (1) WHR is more strongly related to plasma lipoproteins than other adiposity measures; (2) there is effect modification by the extent of adiposity for the relation between LDL-cholesterol and WHR; and (3) the adipose distribution may be important in explaining lipoprotein differences between men and women. PMID- 2243253 TI - Random assignment in clinical trials: issues in planning (Infant Health and Development Program). AB - Various options available for the randomization of subjects into groups in a clinical trial are discussed, emphasizing the issues of logistics given less focus in more mathematical treatments. We discuss advantages and disadvantages of total randomization, of Zelen-type randomization procedures, of Efron-type procedures vs more classical blocking procedures to control the balance between groups, and of Simon-Pocock-type procedures vs more classical stratification for controlling possible biases in prognostic factors. Finally, we discuss issues related to choice and implementation of randomization procedures. The discussion is illustrated with the processes of decision-making in a national collaborative randomized clinical trial, the Infant Health and Development Program. PMID- 2243254 TI - Characteristics of individuals and long term reproducibility of dietary reports: the Tecumseh Diet Methodology Study. AB - Food frequency reports in 1967-1969 were compared to frequency reports of the same foods asked retrospectively in 1982-1983 and 1967-1969 for 1184 respondents aged 45-64 years in the Tecumseh Community Health Study. The kappa statistic for concordance of the retrospective and baseline reports was used as a summary measure of the individual's ability to reproduce his or her earlier diet report. Reproducibility was estimated for total diet, represented by 83 foods, and for 9 subsets of foods of epidemiologic interest. In bivariate and multivariate analyses, reproducibility was strongly related to stability of diet; those whose diets changed least over the 15-year period had greatest diet reproducibility. Greater total diet reproducibility was also found among men with higher education, among women of less than 110% desirable weight reporting no special diet and among women reporting no medications. Consistent with current models of memory, the retrospective report of diet was strongly related to the current report of diet. Agreement between the retrospective and baseline diet reports was greater than agreement between the current and baseline diet reports. This indicates that, as a proxy for past diet, the retrospective report of diet is superior to the current report. Similar relationships were found for the 9 subset of foods. PMID- 2243255 TI - An analysis of gestational age, neonatal size and neonatal death using nonparametric logistic regression. AB - The relationship between gestational age, neonatal size and neonatal death is complex. To date, most authors have used birth weight as a proxy for neonatal size and have neglected to examine head circumference and crown heel length. In addition, they have assumed the size and gestational age were linearly related to neonatal death. In this study we use nonparametric multiple logistic regression to examine the relationship between gestational age, neonatal size and neonatal death. On its own, gestational age was nonlinearly associated with neonatal death. This nonlinearity disappeared with the addition of birth weight, crown heel length and head circumference. Birth weight, head circumference and crown heel length all had significant nonlinear associations with neonatal death in univariate analysis. With all factors in the model, birth weight and head circumference were nonlinearly associated with neonatal death and crown heel length was linearly associated with neonatal death. The complex relations between gestational age, neonatal size and neonatal death were explored with greater ease with nonparametric logistic regression. PMID- 2243256 TI - Quality control practices in centralized tumor registries in North America. AB - A survey of quality control practices was mailed to 73 central registries in the U.S. and Canada. The response rate was 88%, with respondents representing a wide range of registry characteristics and reporting strategies. While registries expressed different priorities in data use, 80% of respondents felt quality control data were important in the identification of problems. The most common method of quality control was acceptance sampling (used by 97% of respondents), and took the form of visual review, recoding and edit checking. Computer-based edit checks were almost universally used (95%). Process control methods of any sort were used by only 22% of respondents with less than 4% of registries reporting formal quantitative criteria. Sixty-one percent of respondents reported conducting one or more designed studies (e.g. reabstracting or casefinding studies) but only 20% of those made the results public. Greater emphasis should be placed on development of quantitative process controls, experimental design of quality control studies, and formal analyses and reporting of study results. PMID- 2243257 TI - Prepaid versus traditional Medicaid plans: effects on preventive health care. AB - Prepaid, case managed systems have been proposed as a method of controlling costs in Medicaid populations. We investigated the utilization of preventive services in two prepaid Medicaid Competition Demonstration programs in Santa Barbara County, Calif., and Jackson County, Mo. (containing the city of Kansas City). Care in the demonstration sites was compared with care given in similar counties functioning under a traditional fee-for-service Medicaid system--Ventura County, Calif., and St Louis, Mo. We tested the hypothesis that preventive care would be less in the capitated demonstrations. 2735 Children's and 3389 adult's charts were abstracted for care received during the calendar year 1985, after the prepaid demonstration had been in place for more than 1 year. No significant differences were found between the demonstration and comparison counties in the proportion of children with complete DPT or OPV immunizations at 1 year of age, with 56% complete in both California counties and 69 and 65% complete in Jackson County and St Louis, respectively. Regression analysis demonstrated a slight, but statistically significant trend towards more immunizations in the demonstration counties. Pap smear use in women of 15-44 years of age was little different in the California counties, but significantly greater in the Jackson County demonstration in Missouri (64 vs 45%). Physician breast examinations were somewhat more likely to occur in the prepaid, case managed demonstration counties. Capitated, case managed systems for the AFDC Medicaid population appear to result in no diminution of preventive services. Substantial problems exist in this, as in other poor populations, in childhood immunizations. PMID- 2243258 TI - Adverse mortality experience of a southwestern American Indian community: overall death rates and underlying causes of death in Pima Indians. AB - As part of an ongoing epidemiologic study, the death rate and causes of death during 1975 through 1984 were determined in Pima Indians who resided in the Gila River Indian Community (GRIC) in 1965 and later. Death certificates were available for 677 of the 681 deaths. In 78% of the deaths, the underlying cause recorded on the death certificate agreed with the cause determined after review of all available relevant records. The age- and sex-adjusted average annual death rate for the GRIC population (1639/100,000) was 1.9 times (95% CI 1.7-2.0) the 1980 rate for the U.S. all races (878/100,000). In Pima males, whose death rate was substantially higher than that of Pima females, the age-adjusted death rate was 2.3 times that in U.S. males, all races. Moreover among males 25-34 years of age, the Pima death rate was 6.6 times that for the U.S. all races. Diseases of the heart and malignant neoplasms caused 59% of U.S. deaths in 1980, but only 19% of GRIC deaths. By contrast, the age- and sex-adjusted mortality rate in the GRIC Pima was 5.9 times the rate of the U.S. all races for accidents, 6.5 times for cirrhosis, 7.4 times for homicide, 4.3 times for suicide, and 11.9 times for diabetes. Tuberculosis and coccidioidomycosis were important causes of death in the Pima, for whom infectious diseases was the tenth leading cause of death. The findings indicate that programs to improve the adverse mortality experience of the GRIC population should emphasize factors related to fatal accidents, alcoholic cirrhosis, homicide, suicide, diabetes mellitus, and infectious diseases. Young Pimas, especially the males, should be the primary focus of such preventive efforts. These findings and recommendations probably apply to many Native American populations. PMID- 2243260 TI - Is baldness a risk factor for coronary artery disease? A review of the literature. AB - A literature search identified eight articles containing data on both baldness and coronary artery disease (CAD). Three of these articles described case-control studies that showed a positive relationship between baldness and CAD when controlling for CAD risk factors. Three other case-control studies showed no such relationship, but these did not control for CAD risk factors. The results of two cohort studies were inconclusive. Insufficient data were available from these studies to analyze possible relationships between baldness and CAD risk factors themselves. Overall, the data reviewed suggest that a small risk of CAD due to baldness may exist, but this risk is smaller than that of well-known CAD risk factors such as smoking and hypertension. Future research should emphasize proper control for age and CAD risk factors. PMID- 2243259 TI - Health status reports in the care of patients with rheumatoid arthritis. AB - We examined the use of formal health status reports every 3 months over 1 year in the clinical care of patients with rheumatoid arthritis (RA). The reports consisted of single-page, computer-generated summaries of scores derived from either the AIMS (Arthritis Impact Measurement Scales) or the MHAQ (Modified Health Assessment Questionnaire) health status questionnaires. A total of 1920 subjects from 27 community practice sites were randomly assigned to three study groups in each practice: intervention, attention placebo and control. Results showed that 55% of the physicians found the reports to be at least moderately useful as an aid to patient management, primarily for improving the doctor patient relationship. However, no detectable differences among the three groups were seen in terms of medication compliance, number of physician visits, number of referrals, frequency of major medication changes, attitudes towards the physician, patient satisfaction or change in health status over 1 year. The failure to demonstrate objective benefits of health status reports in this study may be due to physician unfamiliarity with health status scores, failure to link the report with an office visit, the relative stability of clinical status in the subjects over 1 year and the relatively short time-frame of the study. PMID- 2243261 TI - Shortcut method to calculate the sample size in trials of screening for chronic disease. AB - One of the first questions arising in the planning of a randomized trial to evaluate mortality reduction by screening concerns the sample size of the trial required to detect an expected mortality reduction in the study group for given significance level alpha, and power 1 - beta. If estimates exist of the underlying average annual incidence rate of the disease ra and the annual mortality rate delta a or survival data for patients in the population under consideration before screening started, then a simple formula for the probability of dying from the disease within T years after entry into the trial can be given for the control group. Standard formulas may then be used for sample size calculations in randomized trials, which compare the risk of death from the disease in the control and the study group accrued at T years after entry. A simple correction for loss of follow-up, due to mortality from other causes or, for instance, migration is possible. PMID- 2243262 TI - Epidemiologic science and public health policy. PMID- 2243263 TI - A clinical ladder for the community health-care setting. PMID- 2243264 TI - The impact of health education on health status: an experimental program for elderly women in the community. AB - Until recently, little research has been conducted on the effect of health education and promotion programs on older adults. As the number of older adults increase and costs for health care skyrocket, educational efforts aimed at delaying the negative effects of chronic illness will become increasingly important. In this study, a pretest-posttest design was used with a 3-month follow-up assessment to determine whether participation in a teacher-directed or learner-paced health education program was related to changes in health-risk status, cholesterol levels, blood pressure readings, or life satisfaction. The program, sponsored by a community health department, enrolled 78 women with a mean age of 71 living in the suburban areas of a large metropolitan county. Women who were randomly assigned to one of the intervention groups were more likely to reduce their stress levels, decrease salt consumption, and decrease their systolic blood pressure. PMID- 2243265 TI - Decision-making authority for family caregivers of the cognitively impaired elderly. PMID- 2243266 TI - Eating behaviors, weight loss methods, and nutrition practices among high school wrestlers. AB - Wrestlers lose weight frequently, using rapid weight reduction methods in order to qualify for a certain weight classification. Under these conditions, the potential for developing eating disorders seems apparent. A questionnaire was used to evaluate binge eating and bulimic behaviors, nutrition practices, and weight loss methods in 716 wrestlers. Subjects lost 4.0 kg, on average, to certify, and cycled (lost and regained) 2.3 kg weekly. Two-thirds gained weight in the postseason. The most frequently used weight loss methods included increased exercise, food restriction, gradual dieting, and heated wrestling rooms. Subjects relied primarily on coaches and fellow wrestlers for sources of weight management. Using symptom severity levels by Hawkins and Clement (1980) and the Diagnostic and Statistical Manual of Mental Disorders (3rd ed.; DSM-III; American Psychiatric Association, 1980) criteria, 2.8% of subjects were classified as bulimic; 1.4% using DSM-III-R (3rd ed.; rev; American Psychiatric Association, 1987); and 1.4% met both DSM-III and DSM-III-R. There were significant differences between the diagnostic (DG) and nondiagnostic groups (NDG) in weight lost to certify, weekly weight fluctuation, postseason weight gain, and severity of binge eating. The DG used fasting, food and fluid restriction, dehydration methods, and laxatives significantly more often to promote weight loss. They also experienced significantly more negative feelings during and following binging. Implications for nursing research and clinical practice are also discussed. PMID- 2243267 TI - Changes in maternal characteristics are predictive of changes in maternal perception of infant temperament. PMID- 2243268 TI - Factors associated with inadequate prenatal care. PMID- 2243269 TI - Cost categories, behavior patterns, and break-even analysis. AB - Nurse executives budget and control costs, use those budgets and other management tools to control departmental costs, identify existing programs to drop or change, target new programs and services, and determine fees for nursing services. Knowledge of costs and their behavior patterns assist nurse executives in all of these activities. The author identifies the two cost categories (direct and indirect), explains the basic cost behavior patterns (fixed and variable), and helps nurse executives identify these cost categories and behavior patterns in their own departments. PMID- 2243270 TI - Expanded nurse autonomy. Models for small rural hospitals. AB - Individual nurse autonomy in hospital settings seems an elusive goal. Models for increasing autonomy appear to have bypassed many small rural hospitals. The power and politics model of organizations helps describe impediments to and opportunities for power that can support autonomous practice. Expanded clinical ladders and modified shared governance are offered as models that can increase nurse autonomy in small rural hospitals that lack the human resources of large urban centers. PMID- 2243271 TI - Physician bonding. The role of the nurse executive. AB - Nurse executives know the significant contributions physicians make to patient care revenues. Healthcare agencies are in fierce competition to attract and retain physicians. The development of a physician "bonding" program is an innovative strategy to build physician loyalty and insure use of agency services. The nurse executive plays a key role in physician relationships. The author presents the role of the nurse executive in the strategic development and implementation of a physician bonding program. PMID- 2243272 TI - Collaborative management. A nursing practice model. AB - The authors discuss an innovative, collaborative management model intended to promote optimal patient care, personal and professional nurse satisfaction, and cost-effectiveness. The model delineates the role components of the nurse manager, the clinical nurse specialist, and the clinical nurse. Although the model is applied to a high-risk antenatal unit, staff members and managers can easily adapt the model to any unit. PMID- 2243273 TI - Chief nurse executive incentive compensation. AB - More and more chief nurse executives (CNEs) are receiving incentive compensation plans. The authors report trends in incentive compensation and discuss what 184 CNEs in multihospital systems said about their incentive compensation plan. PMID- 2243274 TI - What we need to change about nursing. Staff nurses share their ideas. AB - New ways of structuring the delivery of nursing care, recruitment strategies, and retention programs are consistently needed if quality healthcare is to be preserved. The experience described in this article suggests that staff nurses propose creative and pragmatic solutions that enhance those of their managers. The author presents the recommendations of a task force designed to address the challenge of the nursing shortage in order to stimulate similar innovative activities in other settings. PMID- 2243275 TI - When less is more. PMID- 2243276 TI - Management time: who's got the monkey? AB - In any organization, the manager's bosses, peers, and subordinates--in return for their active support--impose some requirements, just as he imposes upon them some of his own where they are drawing upon his support. These demands on him constitute so much of the manager's time that successful leadership hinges on his ability to control this "monkey-on-the-back" input effectively. PMID- 2243277 TI - Ultrastructural aspects of oogenesis and oocyte growth in fish and amphibians. AB - Oogenesis, the early events of primary oocyte growth (meiotic arrest, synapsis, ribosomal gene duplication), and folliculogenesis can be seen to particular advantage in the germinal ridge of the syngnathan ovary. After budding off the germinal ridge (a compartment of the luminal epithelium), nascent follicles then enter into a linear array of developing follicles within which temporal and stage specific events can be correlated with spatial distribution. Prominent features of the later phase of primary oocyte growth include intense transcriptional activity and the formation and subsequent dispersal of the Balbiani vitelline body (mitochondrial cloud) concomitant with an increase in cytoplasmic organelles and volume. Further oocyte growth is characterized by a period of cortical alveolus (in teleosts) or cortical granule (in anurans) formation, in which Golgi elements play a predominant role, and finally vitellogenesis. The latter process, which is responsible for the preponderance of oocyte growth, includes the hepatic synthesis and secretion of vitellogenin (VTG), the uptake of VTG from the bloodstream into the oocyte by receptor-mediated endocytosis, and the transport of VTG via endosomes and multivesicular bodies to forming yolk platelets. In the process, VTG is proteolytically cleaved into the yolk proteins, which assume either a monoclinic (in cyclostomes) or orthorhombic (in teleosts and amphibians) crystalline array. Other structures associated with the growing oocyte are also briefly discussed, including nuage, the vitelline envelope, intercellular junctions between the oocyte and overlying follicle cells, pigment, intramitochondrial crystals in ranidae, and annulate lamellae. PMID- 2243278 TI - Transformation of the amphibian oocyte into the egg: structural and biochemical events. AB - Amphibian oocytes, arrested in prophase I, are stimulated to progress to metaphase II by progesterone. This process is referred to as meiotic maturation and transforms the oocyte, which cannot support the early events of embryogenesis, into the egg, which can. Meiotic maturation entails global reorganization of cell ultrastructure: In the cell cortex, the plasma membrane flattens and the cortical granules undergo redistribution. In the cell periphery, the annulate lamellae disassemble and the mitochondria become dispersed. In the cell interior, the germinal vesicle becomes disassembled and the meiotic spindles form. Marked changes in the cytoskeleton and mRNA distribution also occur throughout the cell. All of these events are temporally correlated with intracellular signalling events: Fluctuations in cAMP levels, changes in pH, phosphorylation and dephosphorylation, and ion flux changes. Evidence suggests that specific intracellular signals are responsible for specific reorganizations of ultrastructure and mRNA distribution. PMID- 2243279 TI - Modification of the Polaron sputter-coater unit for glow-discharge activation of carbon support films. AB - We describe a modification of the Polaron sputter-coater unit series 11 HD enabling activation of carbon support films for electron microscopy of macromolecules and macromolecular assemblies. The modification is simple and the device can be used in two modes, for sputter-coating of SEM samples and for glow discharge activation of carbon support films. Examples of protein-free spreading of DNA and negative staining of bacteriophage particles on activated carbon support films are presented. PMID- 2243280 TI - Transmission electron microscopic x-ray quantitative analysis of human dentin at 200 kV accelerating voltage. AB - Qualitative and quantitative x-ray energy dispersive spectroscopy is now used successfully to analyze many features and processes in inorganic samples. When applied to inorganic samples, however, the results are often less satisfactory due to problems of preparation of organic samples, difficulty of measuring x-rays from organic samples, damage of the sample by the electron beam, and other practical problems. In the present study we used a high voltage transmission electron microscope equipped with an energy dispersive x-ray spectrometer to examine accurate quantitative standardless analysis of thin sections of an organic sample, human dentin. Based on our experiments we found the important parameters for quantitative analysis were sample thickness and appropriate choice of model sample. Further, we show that the method of Cliff and Lorimer can be used with biological samples at 200 kV, and we show that quantitative analysis of human dentin can be carried out at 200 kV. Finally, we show that areas of human dentin can be differentiated by their morphological characteristics and x-ray analyses obtained in the transmission electron microscope. PMID- 2243281 TI - The preparation of cross-sectional transmission electron microscopy specimens of Nb/Al multilayer thin films on sapphire substrates. AB - We have developed a technique for preparation of cross-sectional transmission electron microscopy samples of reacted and unreacted Nb/Al multilayer thin films on sapphire substrates. The choice of substrate was found to be extremely important. Sapphire sputters more slowly than Nb and Nb-compounds and therefore makes it possible to obtain the electron transparent regions in the thin films rather than in the substrate. However, the brittle nature of the sapphire restricts the types of thinning techniques that can be used, requiring extensive ion thinning as a final stage. PMID- 2243282 TI - The need for accurate nutrition survey methodology: the South Carolina experience. AB - Assessment of two nutrition-related risk factors, obesity and fat intake, was completed on a representative sample of South Carolina adults. Obesity estimates determined from self-reported heights and weights were less than prevalences determined from direct measurements (white males 21.4% vs. 28.2%; white females 20.8% vs. 24.5%; black males 29.2% vs. 30.1%; black females 43.6% vs. 50.6%; and total 24.9 vs. 29.8%). Nine fat-intake habits were identified from dietary mannerisms involving the consumption of red meat, fat on meat, fried fish/chicken, butter, eggs, whole milk, bacon/sausage, and cheese and the use of solid fats when cooking vegetables. The mean number of the nine habits exhibited was four. The total number of habits did not correlate well with serum cholesterol, as 27% of the individuals with none of the nine fat intake habits had blood cholesterol values greater than 6.2 mmol/L (239 mg/100 mL), while only 17% of the individuals with seven habits had the high level of cholesterol. These nine habits explained less than 10% of the variability of serum cholesterol values. PMID- 2243283 TI - Nutrition monitoring: interface of science and policy. AB - Information collected through nutrition monitoring efforts is an essential component in the process of effectively translating scientific evidence into public policy. This paper reviews the uses of nutrition monitoring data for policy and program decisions, describes recent progress to strengthen the National Nutrition Monitoring System, and outlines challenges that lie ahead in the nutrition monitoring arena. PMID- 2243284 TI - Selection of nutrition status indicators for field surveys: the NHANES III design. AB - Planning a multipurpose survey in which nutritional status is assessed requires a series of scientific and practical decisions that are constrained by available resources of money and time and by the limits to what can be expected from the respondents. This paper describes the planning process for a multipurpose survey using our experience with the third National Health and Nutrition Examination Survey (NHANES III) as an example. Ideally, the goals and objectives are well defined at the outset, and these guide the development of the survey content and statistical design. Because the needs for information are so great, criteria need to be developed for evaluating which topics will be included in the survey and what tests will be used. In planning the NHANES III, the evaluation criteria used were the scientific merit of the topic, its public health importance, its practical utility to the government, and the feasibility of implementing it within the survey's mode of operation. After the topics to be covered in a survey have been selected, questionnaires and examination protocols are developed, pilot tested, and revised prior to implementing the survey. Procedures are established for providing for informed consent and assuring the confidentiality of findings. PMID- 2243285 TI - Field issues for the plan and operation of the laboratory component of the Third National Health and Nutrition Examination Survey. AB - The design of the laboratory component of a mobile examination survey such as the National Health and Nutrition Examination Survey requires that the physical limitation of the mobile examination center be balanced against the requirements of the laboratory analyses needed to fulfill the goals of the survey. In order to include an analysis in the survey, the scientific merit of the laboratory test must be established and a consensus must be reached on the appropriateness of the technology for the six years of the survey. The public health importance of the analysis and the subsequent results are also evaluated before inclusion into the laboratory protocol. Finally, the feasibility of incorporating the analysis into the protocol is reviewed. The laboratory component of NHANES III is discussed, addressing these points with descriptions of the reasons for inclusion and exclusion of key analytes. PMID- 2243287 TI - Dose-response tests in field surveys. AB - Single static biochemical measures that are commonly used in field surveys often do not capture the dynamic metabolic situation that is most closely related to nutritional status. In contrast, short-term dose-response tests provide more reliable information about nutritional status for some nutrients, but not for others. In vivo response tests for vitamin A and for iron are promising, and in vitro enzyme stimulation tests for thiamin, riboflavin, pyridoxine, and selenium have been widely used. In vivo response tests are constrained by the needs for a waiting period, often for two or more biological samples, and usually for sophisticated instrumentation. In large field surveys, dose-response tests may be best used on a subsample of the population studied. PMID- 2243286 TI - Quality control in planning and operating the laboratory component for the Third National Health and Nutrition Examination Survey. AB - Successfully acquiring high-quality laboratory data for a long-term nutrition survey such as the Third National Health and Nutrition Examination Survey (NHANES III) requires rigorous quality-control procedures throughout the entire design and implementation of the laboratory component. We discuss selection of nutritional biochemistry analyses, proper specimen collection, and the critical need for continuity of protocol during the entire survey. The NHANES III laboratory procedures are described, including specimen collection, processing, shipment to laboratories, and analyses. PMID- 2243288 TI - Methods for assessment of vitamin A status. AB - Assessment of the relative level of vitamin A nutriture in human populations when clinical signs and symptoms of deficiency or of toxicity are absent has presented methodological difficulties. Commonly used indicators include dietary intakes of the vitamin, serum levels, and dark adaptation, all of which have limitations in their precision, especially when applied to individuals and to young children. New and developing nonclinical indicators include the relative dose response (RDR) test or a modification (MRDR) of it, conjunctival impression cytology (CIC), and isotope dilution to estimate total body reserves. These methods, all of which are promising, require additional work to verify their sensitivity, specificity, and predictive power as indicators of relative states of vitamin A depletion for individuals and populations under the many varied conditions commonly associated with an inadequate vitamin status. Currently, the most reliable assessment of vitamin A nutriture is likely when a combination of methods is used. PMID- 2243289 TI - The use and interpretation of assays for vitamin D and its metabolites. AB - Vitamin D is essential for the maintenance of calcium and bone metabolism in humans. The recommended daily allowance (RDA) for vitamin D in the United States of 200 IU (5.0 micrograms) is reasonable for adults who receive some exposure to sunlight; however, in the absence of any exposure to sunlight, this recommendation may be 2 to 3 times lower than that actually required to satisfy the body's needs. Vitamin D was first measured by bioassays. However, bioassays became obsolete in light of the revelation that vitamin D must be activated first in the liver to 25-hydroxyvitamin D (25-OH-D) and then in the kidney to 1,25 dihydroxyvitamin D [1,25(OH)2D] before becoming biologically functional. Current assays measure circulating concentrations of vitamin D, 25-OH-D or 1,25(OH)2D. The serum vitamin D concentration is of value for determining the role of sunlight in producing vitamin D in skin and as a provocative test to determine the absorption of vitamin D in patients with malabsorption syndromes. The serum concentration of 25-OH-D is most valuable for determining the overall vitamin D status of an individual, since it is an average of dietary and sunlight-induced vitamin D. The measurement of the serum 1,25(OH)2D concentrations has been most useful in evaluating disorders in calcium and bone metabolism related to acquired and inborn errors in the conversion of 25-OH-D to 1,25(OH)2D. PMID- 2243290 TI - Assessing calcium status and metabolism. AB - Currently, there is no commonly practiced tool for assessing calcium status of individuals or populations. Few biochemical markers reflect calcium status. Fasting urinary calcium:creatinine ratios may hold promise as an easy, inexpensive method to indicate recent calcium status. Calcium status may best be assessed by integrated measures of calcium assimilation, such as total-body calcium. Although bone-mass measurements do not correlate well with recent dietary intakes of calcium, long-term adequacy of calcium intake influences bone mass. Whether low calcium intakes lead to calcium deficiencies depends on one's ability to adapt and conserve calcium. The relationship between calcium status and a particular disease state, such as osteoporosis, hypertension, or colon cancer, cannot be established until a reliable indicator of calcium status is found. PMID- 2243291 TI - Assessment of zinc status. AB - Plasma zinc concentration has been denigrated as a measure of zinc status because it responds to metabolic conditions unrelated to zinc status and because it is insensitive to changes in dietary zinc. The insensitivity of plasma zinc to reductions in dietary zinc reflects the tremendous capacity of the organism to conserve tissue zinc by reductions in zinc excretion and/or reductions in the rate of growth. Changes in plasma zinc concentrations do not seem to occur until the capacity to reestablish homeostasis by reducing excretion and/or growth has been exceeded. Reductions in dietary zinc beyond the capacity to maintain homeostasis lead to utilization of zinc from a small, rapidly turning over pool. This pool is located, at least in part, in the bone, liver, and plasma. Loss of a small, critical amount of zinc from this pool leads to the rapid onset of both biochemical and clinical signs of zinc deficiency. Thus, plasma zinc is a valid, useful indicator of the size of this exchangeable pool of zinc. Plasma metallothionein concentrations may prove useful for identifying poor zinc status. Plasma metallothionine concentrations reflect hepatic concentrations and, therefore, are reduced when the dietary zinc supply is low. However, since hepatic metallothionein concentrations rise in response to stress, plasma metallothionein concentrations are increased in this state when the plasma zinc concentrations are also likely to be low. Thus, measurement of both plasma metallothionein and plasma zinc concentrations could differentiate a low plasma zinc due to dietary zinc deficiency from a low concentration due to stress, infection, or other metabolic conditions. PMID- 2243292 TI - Assessment of human vitamin C status. AB - Since no reliable functional markers of human vitamin C status have been demonstrated, determination of vitamin C levels in blood plasma and/or leukocytes remains the current choice for individual and population assessments. Newer analytical techniques, especially high-performance liquid chromatography, allow determination of reduced (ascorbic acid), oxidized (dehydroascorbic acid), or total amounts of vitamin C in biological specimens or foods. Plasma levels of vitamin C forms are easily determined but may not reflect tissue content as well as leukocyte levels. The vitamin C content of leukocyte cell types varies severalfold and, unlike plasma, leukocytes may contain an appreciable fraction of dehydroascorbic acid. The effects of sex, age, cigarette smoking, drugs, and physiological factors on vitamin C levels are better known for plasma than leukocytes. To realize the potential of leukocytes as measures of vitamin C status, continued work is needed in standardizing the methodology and interpretive guidelines and simplifying the technique for blood processing. The search for specific functional markers of vitamin C deficiency should continue. Candidate markers may involve pathways of carnitine or collagen metabolism, immunocompetence, or antioxidant defense. PMID- 2243293 TI - Iron: nutrition monitoring and nutrition status assessment. AB - The majority of anemias in the United States are characterized by low mean corpuscular volume and thus are classified as microcytic. Iron deficiency, chronic disease and thalassemia traits are the three leading causes of microcytic anemia. The true cause of anemia must always be sought so that the prevalence estimates of iron deficiency are accurate and so that appropriate treatment can be initiated for the anemic individual. In both the clinical setting and in surveys, the most frequent differential diagnosis of microcytic anemia will involve distinguishing between iron deficiency and chronic disease. Erythrocyte sedimentation rate (ESR), zeta-sedimentation rate (ZSR), and C-reactive protein (CRP) are elevated in a variety of diseases. These indicators may help differentiate the anemia of chronic disease from iron deficiency, so that iron deficiency is not overestimated in hospitalized and aged populations. The red cell distribution width (RDW) appears to be elevated to a greater extent in iron deficiency than in chronic disease or thalassemia traits. RDW and CRP are two of several indicators of iron status in the third National Health and Examination Survey (NHANES III). PMID- 2243294 TI - A review of field techniques for the assessment of energy expenditure. AB - The assessment of energy expenditure in free-living subjects is central to a complete understanding of the etiology of obesity, malnutrition, coronary heart disease, and osteoporosis. Laboratory-based methods that rate high with respect to validity and reliability do not lend themselves to this task because they are restrictive, expensive, or both. Investigators have therefore developed survey methods, physiological markers, and mechanical or electrical monitors for use in the field. The development of the doubly labeled water method for measuring energy expenditure and increased availability of room indirect calorimeters has recently made it possible to evaluate these field techniques. Some of the recently developed mechanical and electrical monitors have been found to be valid for the measurement of energy expenditure, but even the best provide measures that are too variable to be useful on an individual basis. PMID- 2243295 TI - Assessment of protein nutritional status. AB - An evaluation of protein status can be approached by use of anthropometric, clinical, and biochemical data, either singly or in combination, and further aided with dietary data. Each of these approaches has advantages and limitations. Biochemical evaluation has the potential of being the most objective and quantitative. Indicators that have been or might be used include plasma hormone responses to reduced protein intake, plasma levels of specific proteins or specific amino acids, urinary excretion of specific amino acids and other nitrogen-containing compounds, anthropometric and physical measurements of body muscle mass, and functional tests of muscle strength. Several measurements can be combined to produce nutritional indices of broader potential value. The importance of concomitant infection and inflammation, with its many effects on protein metabolism, cannot be ignored in making these assessments. Unfortunately, no single test or group of tests can be recommended at this time as a routine and reliable indicator of protein status. Nonetheless, our increasing knowledge of the metabolism and functions of proteins, together with the recent use of noninvasive stable isotope techniques and of sophisticated physicochemical measurements, provides encouragement that more appropriate indicators are in the offing. PMID- 2243296 TI - Vitamin B-6: a status report. AB - Over the past 50 yr there has been an increased awareness of the importance of vitamin B-6 in human nutrition. The knowledge base for evaluation of vitamin B-6 status has also increased. Indices for vitamin B-6 status can be separated into direct and indirect measures. Among the direct measures, plasma pyridoxal 5' phosphate (PLP) is considered the most relevant. However, measurement of plasma pyridoxal or total vitamin B-6 and urinary 4-pyridoxic acid are also recommended. Indirect measures of vitamin B-6 include the assessment of urinary excretion of xanthurenic acid following a tryptophan load. This is a valid functional index for otherwise healthy persons. Evaluation of erythrocyte transaminase activity and stimulation with PLP provide an estimate of vitamin B-6 intake over an extended period of time. In addition to biochemical measures, determination of vitamin B-6 and protein intake are necessary. Present evidence suggests plasma PLP, urinary 4-pyridoxic acid, at least one indirect measure, and the intake of vitamin B-6 and protein are needed to properly assess vitamin B-6 status. The levels of plasma pyridoxal and erythrocyte PLP are newer measures of status and, with further refinement of methodology, may provide additional insight into vitamin B-6 status. PMID- 2243297 TI - Folate status assessment. AB - This paper is a review of established methods of folate status assessment and the primary factors that increase the risk of folate deficiency, including physiological life cycle changes. The first stage of folate depletion can be assessed by measuring serum folate levels, which drop prior to tissue depletion, and which are paralleled by a reduction in red blood cell (RBC) folate. Functional changes associated with abnormalities in biochemical pathways can be monitored by the deoxyuridine suppression test. Cell division, including erythropoiesis, becomes impaired in the same time sequence as changes in biochemical functions, as evidenced by abnormal erythrocyte morphology and a reduction in hemoglobin concentration. In addition to inadequate dietary folate intake, key factors that may impair folate utilization and thus status include alcohol consumption, smoking, and specific drugs. Folate requirements may increase during various phases of the life cycle due to physiological stresses such as pregnancy and lactation. Folate status may also be compromised during adolescence and in senescence for diverse reasons that require special emphasis on factors such as biological maturity and socioeconomic status, as well as chronic use of alcohol, drugs, and smoking. PMID- 2243298 TI - The importance of context in choosing nutritional indicators. AB - Nutritional indicators are used to screen, diagnose, and evaluate interventions in individuals. They are also used in populations to ascertain and place under surveillance the magnitude of nutritional problems, their location and causes, and to evaluate the impact of programs and policies. Nutritional indicators are also used for research to make inferences about biological and social mechanisms affecting or being affected by nutrition. All these activities include measurements of nutritional indicators, but the choice of indicators, their measurements, analyses, and the need for other data can be very different for inferences from research, for patient management, for making public policy, or for planning or evaluating programs. There is no best indicator, best measure of an indicator, or best analysis of an indicator in a generic sense. The definition of "best" depends ultimately on what is most appropriate for the decision that must be made. This paper gives examples. PMID- 2243299 TI - Dietary intake methodology I. USDA surveys and supporting research. AB - Nationwide food consumption and dietary surveys have been conducted about every 10 yr by the U.S. Department of Agriculture (USDA) since the mid-1930s to fulfill responsibilities for monitoring dietary patterns among the nation's population. Survey findings have implications for policies and programs related to food production and marketing, food safety, food assistance, and nutrition education. Until 1965, these surveys measured household food consumption only, but subsequent surveys were expanded to include food intakes by individuals in the sample households. Since 1985, small-scale continuing surveys of food intakes by individuals have been conducted during the years between the large decennial surveys. The 1-d recall was used in the first dietary intake survey. Then, to capture day-to-day variation in diets, 3 d of intake data, 1-d recall and 2-d records, were collected in 1977-1978, 1987-1988, and 1989. Prior to the 1977-1978 dietary intake survey, USDA embarked upon an intensive program of extramural research that was designed to improve methodologies for surveying individuals' dietary intakes. Since 1975, many major investigations have been completed and results have been incorporated in current survey procedures. Studies included testing of varied recall and diary methods, approaches for validating survey data, debriefings of survey respondents and interviewers, intersurvey comparisons, and testing of panel approaches with in-person, telephone, and mail contacts. PMID- 2243300 TI - Dietary intake methodology. II. USDA's Nutrient Data Base for Nationwide Dietary Intake Surveys. AB - The U.S. Department of Agriculture's (USDA) Nutrient Data Base for Nationwide Dietary Intake Surveys is specifically organized and maintained to analyze data from nationwide dietary surveys within the federal government's National Nutrition Monitoring System. These surveys include the Nationwide Food Consumption Survey and the Continuing Survey of Food Intakes by Individuals conducted by USDA, and the National Health and Nutrition Examination Survey conducted by the Department of Health and Human Services (DHHS). Each public release of the data base covers one or more specific surveys. The data base contains data for energy and 28 components for over 5000 food items. Data are based on the latest information from USDAs National Nutrient Data Bank, the computer-based system used to update USDAs standard reference on food composition, Agriculture Handbook No. 8. An automated system is also used to update the survey nutrient data base with new information released from the Nutrient Data Bank. This system includes three supplementary data sets (primary nutrient data set, recipe file, and table of nutrient retention factors) and a computer program for calculating nutrient content of mixed food items based on nutrient content of their ingredients. Updates are performed at the beginning of new surveys to incorporate the most up-to-date nutrient values. PMID- 2243301 TI - Nutritional assessment of homebound rural elderly. AB - Approximately one quarter of Americans aged 65 and older live in rural areas. Homebound rural elderly are a hard to reach, often poor and frail population. Failure to include homebound rural elderly in nutritional studies may bias representativeness of samples of elderly persons. This paper discusses some challenges in recruiting homebound older persons to participate in nutritional studies and in establishing quality control procedures in a field setting. PMID- 2243302 TI - In-home nutritional assessment of inner-city elderly. AB - Aims of this research have been to obtain aggregate data on reported problems in food access that are experienced by homebound, inner-city elderly; to disaggregate the data to show which subgroups of elderly are at highest risk for these types of food insecurity; and to assess whether these elderly differ socioeconomically, medically, or nutritionally from homebound elderly who report that they eat regularly. Instruments were designed to measure population-based food insecurity and to ask respondents to provide information about their socioeconomic status and disabilities as well as the extent to which they have formal or informal assistance in obtaining food. The need to collect this information has been linked to a state-wide effort to target city nutritionally needy elderly for home-delivered meals. Findings have been that food insecurity in the inner-city homebound is linked to loss of mobility as well as to poverty and lack of in-home food assistance. Minority elderly whose questionnaire responses indicate food insecurity include diabetics whose disease control is adversely affected by irregular eating. When methods of home assessment have been used to examine the extent to which a home-delivered meals program meets the nutritional needs of recipients, it has been possible to demonstrate that meals recipients show less food insecurity than a comparison group on waiting lists to receive meals. PMID- 2243303 TI - Development of indicators to assess hunger. AB - Despite widespread concern about hunger in America, efforts to monitor and assess the extent of hunger have been hampered by lack of consensus on an appropriate meaning for the term hunger and by the lack of valid indicators to assess it. The first phase of the research used qualitative methods to derive a socially appropriate definition of hunger. Thirty-two women in Upstate New York were interviewed regarding their experience with food problems and hunger. The interviews were analyzed using the constant comparative method. Results indicated that women had a narrow and a broad concept of hunger. The narrow concept focused on going without food for a specified period of time and the physical sensation of hunger. The broad one included two dimensions: household and individual hunger. Each had quantitative, qualitative, psychological, and social components. The second phase of the research used survey methodology to examine the validity and reliability of items designed to measure the conceptual definition of hunger. The survey was administered to 189 women in Upstate New York who participated in programs designed for low-income households or households in need of food. The second phase confirmed the conceptualization of hunger developed in the first phase. A subset of valid and reliable items that represented each of the major dimensions and components of hunger was identified as being useful for monitoring and assessing hunger. PMID- 2243304 TI - Progress in the development of a nutritional risk index. AB - The development of a 16-item nutritional risk index (NRI) is chronicled from its inception through its application in three studies designed to assess its reliability and validity. Study I involved a survey of 401 community-dwelling elderly in St. Louis, Missouri who were interviewed at baseline, 4-5 mo later, and 1 yr later. Study II involved a cross-sectional survey of 377 male outpatients attending two clinics at the St. Louis Veterans Administration Medical Center. Study III involved a cross-sectional survey of 424 community dwelling elderly in Houston, Texas. Internal consistency reliability coefficients ranged between 0.47 and 0.60, and test-retest reliability coefficients ranged between 0.65 and 0.71. Validity was established by using the NRI to predict the use of health services, as well as by correlating it with a variety of anthropometric, laboratory, and clinical markers of nutritional status. The utility of the NRI for future applications is discussed. PMID- 2243305 TI - Core indicators of nutritional state for difficult-to-sample populations. AB - Previous expert working groups have concluded that common descriptors and measurements are needed for all types of population groups to provide improved and expanded coverage and comparable and compatible data among surveys monitoring the nutritional and dietary status of the U.S. population. This report summarizes the discussions of an ad hoc Expert Panel charged with identifying core indicators to assess the nutritional status of difficult-to-sample populations. Members of the Expert Panel had wide research experience including survey design, food security, food consumption, nutritional status, health-related conditions associated with nutritional status, and nutrition and public policy. The varied backgrounds of the Panel members led to consideration of the concept of core indicators of nutritional status from a broad perspective. Early in their discussions the Expert Panel recognized that public health officials and policymakers use information on nutritional status for the purposes of problem identification, program planning and resource direction, and program and policy evaluation. This recognition raised several issues which formed the conceptual framework for subsequent discussions, study conclusions, and research recommendations. These issues centered on the following concepts: the purpose for which data are used determines the suitability of indicators; the scope of information required varies for the purposes identified above; a broad range of indicators is needed to supply information useful for public policy decisions on nutrition; that is, assessment of the nutritional status of populations by measurement of dietary intakes of nutrients and anthropometric, biochemical, and clinical indices can provide only a portion of the information needed for these purposes in the United States; nutritional problems in the U.S. general population may signal some, but not all, anticipated nutritional concerns for difficult-to-sample populations; and, adequate coverage and suitable sampling methods are overriding concerns for obtaining interpretable data and appear to be a larger issue than suitable measures for nutritional assessment in the case of difficult-to-sample populations. Guided by consideration of these issues, the Expert Panel recognized that they could not provide a comprehensive design for the evaluation of nutritional status for all difficult-to-sample populations that would be appropriate for all public health and policy purposes. Therefore, the Expert Panel concentrated their discussions on enumeration of the various issues that must be considered in planning any effort to evaluate the nutritional concerns for such populations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2243306 TI - Clinical evaluation of elastomeric hydrogel peripheral catheters during home infusion therapy. PMID- 2243307 TI - Impact on patient care. 2652 PIC catheter days in the alternative setting. AB - Management of parenteral therapies in the home or nonacute setting is essential. Peripherally inserted long-line catheters establish venous access in patients in a safe, cost-effective, and improved manner. Data were collected on 130 cases from 24 offices in 16 states. The most frequently occurring types of therapies used were antibiotic, pain control, and parenteral nutrition. Average length of therapy was 20.4 days. The major reasons for catheter removal other than completion of therapy (58%) were occlusion (14%), breakage (5%), and phlebitis (4%). PMID- 2243308 TI - Home pain management. Continuous infusion of narcotics. AB - Home pain management is a complex and challenging therapy for the home infusion nurse. A thorough knowledge of pain assessment, therapeutic approaches, and pharmacology of narcotics; management of side effects; and a recognition of individual variations in response are necessary for successful pain control. Continuous infusions of narcotics can be safely administered in the home setting, thus leading to an improved quality of life for patients with intractable pain. A retrospective chart review of 20 patients cared for by Deaconess Home Health Care Corporation in Boston, Massachusetts, illustrates the wide variation in individual narcotic requirements necessary to achieve pain control. Three case studies are also included to provide further comparison. PMID- 2243309 TI - Advanced central venous access. Selection, catheters, devices, and nursing management. AB - The increased need for intravascular access in the care of a variety of patients is, in part, responsible for the diversity of central venous access devices. Various nontunneled catheters, tunneled catheters and implantable ports are available on the health care market. As the availability of these devices increases, so must the nurse's knowledge base in order to provide optimal safe care to patients using different devices. Learning which device is best suited for each patient and which has the fewest known complications can be a tedious process for the nurse specialized in venous access care. PMID- 2243310 TI - Intraperitoneal therapy via the Tenckhoff catheter. Prevention and management of complications. AB - Mathematical modeling and clinical trials have increased the use of intraperitoneal (IP) therapy in cancer care. A direct result of this increase in IP therapy research is an increasing use of access devices. One of the most commonly selected access devices is the Tenckoff catheter. The prevention and management of complications of IP therapy via the Tenckhoff catheter are nursing's responsibility. Complications include peritonitis, catheter occlusion, exit site infections, leakage of fluid from around the catheter, and chemical peritonitis. Nurses' expertise in this area as clinicians and patient educators contributes to the success of IP therapy. PMID- 2243312 TI - Journal of Cardiology. Cumulative index. 1971-1987. PMID- 2243311 TI - A neonatal home intravenous antibiotic therapy program. AB - Home intravenous therapy offers many benefits for children as well as adults. Infants less than 1 month old may also benefit from home I.V. therapy. Neonates are a unique group of home I.V. therapy recipients, and providing safe home I.V. therapy for them requires changes in standard home I.V. policies and procedures. PMID- 2243313 TI - The HIV cytopathic effect: potential target for therapy? AB - HIV kills activated infected CD4+ T cells after a burst of replication and the release of large numbers of virions. From a review of the literature on HIV regulatory genes and from preliminary mathematical models of HIV dynamics at four levels (host population epidemiology, the immune system, gene regulation within infected cells, and selection of mutants) we have arrived at the theory that in the etiology of HIV the HIV cytopathic effect may actively be caused by a viral regulatory gene product. The most likely candidate is the rev regulatory protein. Rev and the analogous rex protein from HTLV-I (human T cell leukemia virus) both have two active sites with similar function: one site locates the protein in the nucleus/nucleolus, and the other site interacts with viral mRNAs, facilitating their export from the nucleus to the cytoplasm. Rev seems to have a third functional site near the 3' end. We conjecture that this site may be responsible for the cytopathic effect. We think that rev acts on cellular genes that normally induce senescence and cell death during development, or T-cell maturation, or on terminal differentiation. We propose that mathematical and computer models of the immune system could be used to explore whether suppression of the cytopathic action of the rev protein could be of therapeutic benefit in restoring the ability of the immune system to clear HIV or at least to extend latency. We also suggest how immune deficiency disease might be created as laboratory artifact in animal populations. PMID- 2243314 TI - Mathematical models of HIV infection. I. Threshold conditions for transmission and host survival. AB - This is the second in a series of papers modeling human immunodeficiency virus (HIV) infections at four levels: transmission, interaction with the immune system, gene regulation, and selection of mutants. In the previous paper (1) we described and presented a theory of the HIV cytopathic effect based upon the models (and a review of the literature). In this article we give mathematical equations of threshold conditions that connect infectivity, length of host survival, and frequency of acts conducive to transmission. The formula is derived not only for homogeneous populations but also for populations of an arbitrary number of subgroups with varying frequencies of risk behavior, varying rates of infection and latency periods, and varying frequencies of interaction with other groups. PMID- 2243315 TI - p21rex protein of HTLV-1. AB - Virion protein expression of the human T-cell leukemia virus type 1 (HTLV-1) is regulated by p27rex. This protein is expressed by a doubly spliced mRNA encoding an additional protein, p21rex. p27rex has been shown to increase the amount of unspliced viral mRNAs encoding envelope and capsid proteins. To assess a possible contribution of p21rex to the rex regulation, a point mutation was introduced into the p21rex initiation codon. Expression of env and gag plasmids, transfected in Jurkat cells, was dependent only upon p27rex expression and was not affected by the absence of p21rex. Consequently, the rex regulation of the HTLV-1 structural genes can be solely attributed to the p27rex protein. PMID- 2243316 TI - Isolation of HIV-1 from the blood of seropositive adults: patient stage of illness and sample inoculum size are major determinants of a positive culture. The Walter Reed Retroviral Research Group. AB - Results of HIV-1 blood cultures from 609 seropositive adults across all stages of illness at the Walter Reed Army Medical Center were reviewed. HIV-1 was isolated by coculturing of patient peripheral blood mononuclear leukocytes (PBMCs) with normal blood donor target PBMCs that had been stimulated with phytohemagglutinin and interleukin-2. The HIV-1 isolation success rate at Walter Reed increased progressively each year from 1986 to 1989. In 1989, HIV-1 was isolated from a single blood specimen from patients in Walter Reed stages 1-2, 3-4, and 5-6 in 75% (49/65), 90% (37/41), and 97% (30/31) of cases, respectively. None of 22 blinded negative control specimens was positive. PBMC cultures from late stage patients regularly became positive within 7 days (92%), compared to only 46% of positive cultures from early stage patients. For most patients, the lowest number of serially diluted PBMCs that resulted in a positive culture was 30,000 patient PBMCs, but the range was 300 to 3 million cells. HIV-1 was isolated less frequently from plasma (5/18, 28%). Plasma viremia was detected only in patients with relatively high titers of infected PBMCs. Forty-six blood specimens from "at risk" seronegative adults were also cocultured; none was positive. PMID- 2243317 TI - Tracking the spread of the HIV infection epidemic among young adults in the United States: results of the first four years of screening among civilian applicants for U.S. military service. AB - Because the period from infection to clinically apparent disease is long, variable, and changing as new therapies are developed and applied, AIDS data are inadequate for tracking current values of critical parameters of HIV infection epidemics: prevalence of infection, rate of acquisition of new infections (incidence rate), and direction and rate of change of infection incidence over time (acceleration). These "vital signs" of infection epidemics can be tracked using serial cross-sectional seroprevalence data, however. From October 1985 through September 1989, more than 2.3 million applicants for U.S. military service were screened for antibody to HIV. The overall seroprevalence was 1.31 per 1,000 (3,014/2,300,675). Seroprevalences were highest near urban centers of the AIDS epidemic and were independently associated with age, race/ethnicity, and gender. Based on age seroprevalence trends, it was crudely estimated that at least one of 2,000 young men and one of 7,000 young women are infected with HIV annually in the U.S. Infection incidence rates, estimated from age and temporal trends, were estimated to be highest among black males (1.40/1,000/year) and lowest among white females (0.03/1,000/year). Poisson regression analysis of seroprevalence trends suggested that infection incidence rates accelerated among black females during the first 3 years of screening. Since selection factors undoubtedly changed over the period, estimates based on these data probably underestimate actual values in the general population, particularly near urban AIDS epicenters. Nonetheless, even crude estimates of these critical values, particularly among adolescents and young adults, are useful to guide policy development, to allocate resources, and to monitor program effects. PMID- 2243318 TI - Relapse from safer sex: the next challenge for AIDS prevention efforts. AB - Prevention campaigns to reduce sexual transmission of human immunodeficiency virus (HIV) typically emphasize the initial adoption of safer sex techniques. We present data from a 5-year prospective study to show that the vast majority of resident gay men in San Francisco have made these initial risk reductions. Rather, relapse from safer sex techniques is now the predominant predominant kind of high-risk sex, accounting for approximately two thirds of all prevalent high risk sex in the 1988 wave of data collection. Predictors of relapse from safer sex are identified, and these are discussed in terms of their implications for preventing relapse from the exclusive practice of safe sex. In communities that have already manifested widespread behavioral risk reductions and in which HIV infection is highly prevalent, finding ways to prevent relapse of behavioral risk reductions will be the next important challenge in the fight against acquired immune deficiency syndrome. PMID- 2243320 TI - Does HIV cause AIDS? PMID- 2243319 TI - Seroprevalence of HIV-2 infection in Greece (Crete). AB - The seroprevalence of HIV-2 was evaluated in 20,407 consecutive normal blood donors, 100 homo- and/or bisexuals, and 7,020 heterosexuals presenting for an HIV test using an EIA test. Sixty-seven sera were revealed to be repeatedly positive. Analysis by Western blot confirmed the infection in four cases, an indeterminate (antibodies against only the gag-encoded proteins) pattern was revealed in 25 cases, whereas 38 sera were negative. Three of the four HIV-2-positive sera also reacted with two distinct, but close, synthetic peptides homologous to viral gp36. The fourth serum, which did not display antibodies against gp36 on Western blot, did not react with gp36-derived synthetic peptides. None of these sera reacted with native HIV-1 antigens or synthetic peptides homologous to gp41. Sera with an indeterminate HIV-2 Western blot did not react with gp36-derived synthetic peptides. Although 10 of them also displayed an indeterminate HIV-1 Western blot, no serum sample reacted with two gp41-derived synthetic peptides or proved to be positive when they tested for p24 antigen. One bisexual and one heterosexual HIV-2 positive subject reported sexual contacts with West Africans, whereas two other heterosexuals had had multiple sexual partners from different countries. PMID- 2243321 TI - HIV-1 and HTLV-1 infections among intravenous drug abusers in Belgrade, Yugoslavia. PMID- 2243322 TI - Spontaneous lymphocyte proliferation in vitro characterizes both HTLV-I and HTLV II infection. PMID- 2243323 TI - Toward a concept of triage for labor and delivery: staff perceptions and role utilization. PMID- 2243324 TI - The effects of rocking, diet modifications, and antiflatulent medication on postcesarean section gas pain. PMID- 2243325 TI - Obstetric and gynecologic abdominal wound infections: a comprehensive nurse managed program. PMID- 2243326 TI - Prevention of Preterm Labor Project in a public hospital: breaking down barriers to prenatal care. PMID- 2243327 TI - Ostomy care for the infant with necrotizing enterocolitis: nursing considerations. PMID- 2243328 TI - Hyperviscosity-polycythemia syndrome: a case study. PMID- 2243329 TI - Mentorship: the key to the future of professionalism in nursing. PMID- 2243330 TI - Caring for the NICU parent. PMID- 2243331 TI - L-tyrosine potentiates the anorexia induced by mixed-acting sympathomimetic drugs in hyperphagic rats. AB - The effects of L-tyrosine (L-TYR) on the anorectic activity of several mixed acting sympathomimetics were determined during the dark cycle in rats made hyperphagic by food deprivation. L-TYR (200 mg/kg) significantly potentiated the anorectic activity of phenylpropanolamine, (-)-ephedrine and (+)-amphetamine by 48, 50 and 37%, respectively. When the dose of L-TYR was varied (25-400 mg/kg), a significant dose-dependent relationship was noted. The observed potentiation was positively correlated with increases in brain TYR concentrations; blockade of L TYR uptake into the brain by the coadministration of L-valine prevented this potentiation. Various other L-amino acids, as well as D-TYR, failed to mimic the potentiating action of L-TYR. As determined by alpha-methyl-p-TYR pretreatment, the L-TYR-induced potentiation was dependent upon increased catecholamine synthesis. Although various other mixed-acting sympathomimetic anorexiants were similarly potentiated by L-TYR, the direct-acting beta-2 adrenoceptor anorexiants, salbutamol and methoxyphenamine, were not. These results indicate that L-TYR specifically potentiates the anorectic activity of the studied mixed acting sympathomimetics and are consistent with the requirement of the central conversion of L-TYR to catecholamines via TYR hydroxylase for this response. The possibility that the effect of mixed-acting sympathomimetics is normally limited by the availability of L-TYR is suggested. PMID- 2243332 TI - Suppressive effects of morphine pellet implants on in vivo parameters of immune function. AB - Chronic morphine treatment elicits a variety of immunosuppressive effects in mice. Most of the work describing this immuno-suppressive activity of the opioid is based on in vitro assessments of the performance of certain components of the immune system in morphine-treated animals. Relatively little has been done by way of tracking the effects of chronic morphine treatment on immunologic parameters in the intact animal. Therefore, this study used several classic in vivo determinations of immune function in mice treated chronically with morphine. Morphine pellet (75 mg) implantation led to a significant inhibition (91%) of paw swelling in a picryl chloride-induced delayed type hypersensitivity response. Uptake of iododeoxyuridine in an in vivo lymphocyte proliferation assay and splenomegaly in a graft vs. host reaction were also significantly suppressed by morphine pellet implantation (34 and 52%, respectively). Coimplantation of a naltrexone pellet (10 mg) completely reversed the suppressive responses to morphine in each assay. Naltrexone alone had no significant effect in any of the assays. The suppressive effects of morphine were less pronounced in adrenalectomized mice in the graft vs. host assay (51% vs. 9% reduction in morphine-pelleted shams relative to morphine-pelleted adrenalectomized mice). These findings indicate the pathophysiologic significance of the previously reported suppression of in vitro correlates of immune function in morphine pelleted mice. The results further demonstrate that the immunosuppressive effects observed after morphine pellet implantation are naltrexone reversible and suggest that activation of the adrenal is one potential mechanism for this effect. PMID- 2243333 TI - CRE 10904 [2-(p-fluorophenoxy), 1-(o-hydroxyphenyl)-ethane]: a new diuretic and antihypertensive drug acting by in vivo sulfation. AB - CRE 10904 [2-(p-fluorophenoxy), 1-(o-hydroxyphenyl)-ethane, the leading compound of a new family of loop diuretic and antihypertensive agents: 1-aryl, 2-aryloxy ethanes] induced high-ceiling natriuretic action in dogs and rats, but was completely inactive in pigs. High-performance liquid chromatography determinations revealed that all CRE 10904 (p.o. or i.v. administered) was rapidly sulfo-conjugated in dogs and rats, and glucurono-conjugated in pigs. The (O-sulfonyl)-CRE10904 metabolite (or simply CRE 11296) rapidly appeared in plasma, reached a concentration peak at about 40 min and disappeared with a half life time of about 3 hr. The urinary excretion of CRE 11296 was correlated with the natriuretic activity of CRE 10904. Moreover, CRE 11296 was a powerful natriuretic compound in rats and dogs and, even in pigs, i.v. CRE 11296 induced transient natriuresis (just before its rapid hydrolysis and glucurono conjugation). Studies in human red blood cells revealed that: 1) CRE 11296 was a potent inhibitor of the [Na+,K+,Cl-]-cotransport system (IC50 of 1.5 +/- 0.3 x 10(-5) M; mean +/- S.E.M. of 5 experiments), slightly more powerful than furosemide (IC50 of 2 x 10(-5) M), 2) it was the only diuretic drug potently inhibiting the [K+,Cl-]-cotransport system (IC50 of 2.1 +/- 0.6 x 10(-5) M; N = 3) and the [Cl/HCO3-] exchanger (IC50 of 4.5 +/- 1.0 x 10(-5) M; N = 3) and 3) CRE 10904 and its glucuronide were much less potent Cl- transport inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243334 TI - Calcitonin gene-related peptide is the endogenous mediator of nonadrenergic noncholinergic vasodilation in rat mesentery. AB - In the isolated perfused rat mesenteric vascular bed pretreated with guanethidine and precontracted with methoxamine, periarterial nerve stimulation elicited a frequency-dependent and endothelium-independent vasodilation. The sustained vasodilation was slow-onset and reversible. It was resistant to propranolol or atropine but sensitive to tetrodotoxin and capsaicin suggesting that this is a nonadrenergic-noncholinergic vasodilation and is a neurogenic response. The vasodilation was abolished by anti-serum against calcitonin-gene related peptide (CGRP) in a concentration-dependent manner. These data suggest that the non adrenergic-noncholinergic vasodilation is mediated by endogenous CGRP released from the primary sensory nerve terminals upon electrical stimulation. In addition to the vasodilator action, CGRP also inhibited nerve stimulation-induced and norepinephrine-induced vasoconstriction at extremely low concentrations. The inhibitory action of CGRP appeared to be mediated by postsynaptic mechanisms inasmuch as evoked norepinephrine release was not affected by CGRP when the vasoconstriction produced by norepinephrine or periarterial nerve stimulation was attenuated greatly by CGRP. These observations suggest that the vascular tone of the resistance vessels can be regulated by primary sensory nerve-derived CGRP. PMID- 2243335 TI - Modulation of ATP-sensitive K+ channel activity and contractile behavior in mammalian ventricle by the potassium channel openers cromakalim and RP49356. AB - We have investigated the effects of potassium channel opening drugs on the ATP dependence of ATP-sensitive K+ channel activity and on contractile activity in rat and guinea pig ventricular myocytes. The results show that cromakalim (BRL34915), and RP49356, agents reported to open ATP-sensitive K+ channels, do so by shifting the intracellular [ATP] required to cause half-maximal inhibition of channel activity (ki) to higher [ATP]. In guinea pig ventricular myocytes at 37 degrees C, the ki was shifted from 79 to 152 microM by 40 microM cromakalim and, in rat myocytes at room temperature, the ki was also shifted to higher [ATP] by 50 microM RP49356. The effect of externally applied RP49356 on the contractile activity of intact rat ventricular myocytes was investigated. At 100 microM the drug was without effect in the presence of normal bathing solution containing 10 mM glucose. When glucose in the bathing medium had been replaced by 2 deoxyglucose for 84 +/- 2 min, 100 microM RP49356 decreased the twitch amplitude to 23 +/- 4% of control. The negative inotropic effect of 100 microM RP49356 increased with time after perfusion with 2-deoxyglucose, and the negative inotropic effect diminished on reperfusing with glucose; 83 +/- 3 min after reperfusing with glucose, twitch amplitude was decreased by only 52 +/- 6% on exposure to 100 microM RP49356. These results suggest that the effect of the potassium channel opening drugs on contractility and electrical behavior will depend critically on the intracellular [ATP]. The results provide an explanation of how potassium channel openers may become clinically useful as cardioprotective agents without interfering with normal function. PMID- 2243336 TI - Opiate-receptor antagonist improves metabolic recovery and limits neurochemical alterations associated with reperfusion after global brain ischemia in rats. AB - Opiate-receptor antagonists improve behavioral, electrophysiologic and/or histologic outcome in various experimental models of central nervous system ischemia. To address the potential mechanism(s) by which opiate-receptor antagonists may exert their protective actions in cerebral ischemia, metabolic and biochemical changes were measured in brain of rats pretreated with the opiate receptor antagonist nalmefene or vehicle and subjected to 60 min of global ischemia followed by 2 hr of reperfusion. 31P and 1H magnetic resonance spectroscopy were used to follow the metabolic changes during ischemia and reperfusion, after which brain tissue was frozen in situ. Biochemical assays included free fatty acids, thromboxane B2, ascorbate, vitamin E and amino acids. Nalmefene-treated animals showed more rapid and complete recovery of cellular bioenergetic state (as indicated by the phosphocreatine to inorganic phosphate ratio), tissue acidosis and lactate levels during reperfusion than placebotreated controls. Ischemia/reperfusion caused significant increases of fatty free acids and thromboxane, associated with significant decreases of ascorbate and glutamate; nalmefene pretreatment limited each of these changes. The degree of metabolic improvement as reflected by recovery of high energy phosphates and reduction of lactic acidosis were highly correlated with changes in tissue levels of arachidonate and glutamate. Thus, the beneficial effects of opiate-receptor antagonists in cerebral ischemia may be due, in part, to an ability to enhance metabolic recovery with associated, reduction in phospholipid hydrolysis and excitotoxin release. PMID- 2243338 TI - Protective effect of a novel calcium blocker, S-312-d, on ischemic acute renal failure in rat. AB - The effect of the calcium blocker S-(+)-methyl 4,7-dihydro-3-isobutyl-6-methyl-4 (3-nitro-phenyl)thieno[2,3-b]pyridine- 5-carboxylate (S-312-d) on ischemic acute renal failure (ARF) was studied in rats. Ischemic ARF was induced by temporary (30-60 min) clamping of the left kidney 2 weeks after contralateral right nephrectomy. Plasma creatinine, creatinine clearance, urinary osmolality and fractional excretion of sodium were used to test the effectiveness of the drug. S 312-d (0.01-0.1 mg/kg b.wt. i.v.) administration before ischemia offered dose dependent protection against the functional impairment induced by ischemia. This effect was accompanied by an increase in the survival rate of ischemic rats. S 312-d given after ischemia was not effective. The renal cortical edema induced by ischemia was significantly reduced by pretreatment with S-312-d. The increase in renal tissue calcium content observed after ischemia was also suppressed by S-312 d. Comparison with other established calcium blockers indicated S-312-d to be a good candidate for protection against ischemic ARF. These findings indicate that S-312-d may be clinically useful against renal ischemia. PMID- 2243337 TI - Endothelium-mediated effects of N-substituted arginines on the isolated perfused rat kidney. AB - Endothelium-derived relaxing factor (EDRF) has been suggested to be derived from the metabolism of arginine or an arginine-containing moiety. We have compared the vascular effects of arginine and some of its N-substituted derivatives on the perfusion pressure (Pp) of the isolated rat kidney preparation preconstricted with phenylephrine. Irrespective of the stereochemistry, high doses (10(-4) mol) of L- and D-arginine HCl produced a slight vasodilation. In contrast L- and D arginine free base, at similar doses, further increased renal Pp. N-substituted L arginine compounds, however, decreased Pp dose-dependently. Their order of potency (ED50) was as follows: N-alpha-benzoyl-L-arginine ethyl ester (BAEE, 3.8 x 10hm6 mol) greater than N-alpha-benzoyl-L-arginine methyl ester (2.5 x 10(-5) mol) greater than L-arginine ethyl ester (2.7 x 10(-5) mol) greater than L arginine HCl (10(-4) mol). Methylene blue (10(-5) M), hemoglobin (10(-5) M) and NG-mono-methyl-L-arginine (5 mumol) antagonized the vasodilation elicited by infusion of BAEE. Similarly, injection of xanthine oxidase/xanthine (100 mU) reversed BAEE-induced renal vasodilation, but had no effect on dilation elicited by infusion of atrial natriuretic peptide. These data demonstrate that substituted arginine compounds are more potent renal vasodilators than L-arginine and their potency depends on the nature of the substitution. These compounds exert their effect, at least in part, via an endothelium-dependent mechanism. We conclude that exogenous L-arginine is a poor substrate for EDRF generation in the kidney, and that it may cause release of EDRF by another mechanism, possibly related to a change in the pH of the medium. PMID- 2243339 TI - Renal disposition and effects of naproxen and its l-enantiomer in the isolated perfused rat kidney. AB - Renal handling, metabolism and effects on kidney function of naproxen and its l enantiomer were examined in the isolated perfused rat kidney (IPK). Urinary excretion rate of naproxen was much lower than the filtration rate, indicating extensive reabsorption. Naproxen is accumulated considerably in the IPK. This accumulation is concentration-dependent and is probably the result of active secretion of naproxen. Considerable amounts of desmethyl-naproxen were formed in the IPK. The kinetic behavior of the l-enantiomer of naproxen did not differ from naproxen. Addition of 37.5 to 3750 micrograms naproxen caused a decrease in urinary flow, glomerular filtration rate and fractional excretion of sodium, chloride, potassium, magnesium and calcium. The presence of prostaglandin E2 in the perfusate fully opposed the effects of naproxen on kidney function. Addition of 375 micrograms l-enantiomer of naproxen did not influence kidney function. Addition of very high doses (1 x 10(5) micrograms) of naproxen and its l enantiomer to the IPK caused diuresis and increased the fractional excretion of sodium, chloride, potassium, glucose and calcium. We conclude that the pharmacokinetic behavior and the metabolism of naproxen in the IPK is probably not stereoselective; that relatively low doses of naproxen exert a specific, stereoselective effect on kidney function caused by inhibition of the prostaglandin E2 synthesis and that high doses of naproxen exert a nonstereoselective effect on kidney function. PMID- 2243340 TI - Pharmacology of pravadoline: a new analgesic agent. AB - Pravadoline is a new chemical entity with analgesic activity in humans. This report describes the pharmacology of pravadoline and compares the activity of pravadoline with that of two major classes of analgesics, the opioids and the nonsteroidal anti-inflammatory drugs (NSAIDs). Like the NSAIDs, pravadoline inhibited the synthesis of prostaglandins (PGs) in mouse brain both in vitro (IC50, 4.9 microM) and ex vivo (ED50, 20 mg/kg p.o.) and displayed antinociceptive activity in rodents subjected to a variety of chemical, thermal and mechanical nociceptive stimuli. Administration of pravadoline prevented the writhing response induced by i.p. administration of acetylcholine (ED50, 41 mg/kg p.o.) or PGE2 (ED50, 24 mg/kg p.o.) and prolonged the response latency induced by tail immersion in hot water at a temperature of 55 degrees C (minimum effective dose, 100 mg/kg s.c.). In the rat, treatment with pravadoline prevented acetic acid-induced writhing (ED50, 15 mg/kg p.o.), brewer's yeast-induced hyperalgesia (Randall-Selitto test) (minimum effective dose, 1 mg/kg p.o.), the nociceptive response induced by paw flexion in the adjuvant-arthritic rat (ED50, 41 mg/kg p.o.) and bradykinin-induced head and forepaw flexion (ED50, 78 mg/kg, p.o.). The antinociceptive activity of pravadoline cannot be explained by an opioid mechanism, because pravadoline-induced antinociception was not antagonized by naloxone (1 mg/kg s.c.) and pravadoline did not bind to opioid receptors at concentrations up to 10 microM. However, like the opioid analgesics, pravadoline diminished the electrically induced twitch response of mouse vas deferens preparations, but, in contrast to opioids, this action of pravadoline was not attenuated by naloxone. The possibility is discussed that this effect of pravadoline upon isolated tissues may contribute to its antinociceptive activity. In contrast to NSAIDs, pravadoline was more potent ex vivo as an inhibitor of the formation of PGs in brain vs. stomach. In addition, pravadoline failed to produce gastrointestinal lesions when administered p.o. to rats or mice, and did not possess significant anti-inflammatory activity at antinociceptive doses. Also unlike NSAIDs, pravadoline inhibited rat gastrointestinal transit when administered at doses similar to those which were antinociceptive. The overall pharmacologic profile of pravadoline suggests that the compound may be capable of managing more diverse or more severe pain than is achieved by anti-inflammatory analgesics, without producing side effects commonly associated with either the opioid or the nonopioid analgesics. PMID- 2243341 TI - A comparison of the effects of cholinergic and dopaminergic agents on scopolamine induced hyperactivity in mice. AB - The effects of cholinesterase inhibitors, cholinergic agonists, dopaminergic agonists and dopaminergic antagonists on the hyperactivity produced by the muscarinic cholinergic antagonist scopolamine were evaluated in mice. Scopolamine (0.3-10 mg/kg) produced a dose-related increase in locomotor activity, with a peak effect at 3.0 mg/kg. The cholinesterase inhibitor physostigmine (0.03-0.175 mg/kg) was without effect on locomotor activity when administered alone, whereas the cholinesterase inhibitor tetrahydroaminoacridine hydrate (0.3-10 mg/kg) decreased locomotor activity. Both physostigmine and tetrahydroaminoacridine hydrate attenuated the effects of scopolamine. Administered alone, the cholinergic agonists oxotremorine (0.01-0.3 mg/kg) and RS86 (0.1-3.0 mg/kg) produced dose-related decreases in locomotor activity, whereas pilocarpine (0.3 10 mg/kg) had no effect on locomotor activity. None of these three muscarinic agonists significantly attenuated the hyperactivity produced by scopolamine. Administered alone, the dopaminergic agonists quinpirole (0.003-0.1 mg/kg), S-(-) 3-(3-hydroxyphenyl)-N-n-propylpiperidine (0.3-10 mg/kg) and SKF 38393 (8-64 mg/kg) had no significant effect on activity, whereas apomorphine (0.3-10 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) increased activity. Quinpirole, apomorphine and S-(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine produced dose-related reversals of the increases in locomotor activity produced by scopolamine. The hyperactivity effects of d-amphetamine were approximately additive with scopolamine, whereas SKF 38393 did not significantly affect scopolamine. The mixed D1/D2 dopaminergic antagonist haloperidol (0.003-3.0 mg/kg) and the selective D1 antagonist SCH 23390 (0.01-0.3 mg/kg) produced dose-related decreases in locomotor activity when administered alone, and also produced dose-related reversals of the hyperactivity produced by scopolamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243342 TI - On the metallothionein, glutathione and cysteine relationship in rat liver. AB - Stress and starvation increased liver metallothionein (MT) and decreased liver glutathione (GSH) levels. Serum cysteine plus cystine levels were increased by stress. The exogenous administration of GSH, while not modifying hepatic GSH content, increased liver MT levels in basal and starved rats but not in stressed rats. Liver and serum cysteine levels were increased by GSH administration, a process partially reverted by the irreversible inhibitor of gamma-glutamyl transpeptidase, alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid. Mouse and rat liver MT levels were also increased by buthionine sulfoximine, an inhibitor of GSH synthesis, indicating that GSH is not a necessary precursor of MT. In addition, the hepatic MT content was increased by the administration of cysteine in a dose-response manner. These results suggest that hepatic MT synthesis is elevated by increased cysteine pools, and that MT, GSH and cysteine levels are somehow inter-related. MT, besides GSH, may be contemplated as a putative intracellular reservoir of cysteine in the liver of adult rats. PMID- 2243343 TI - Effect of aging on hepatic biotransformation in female Fischer 344 rats: changes in sulfotransferase activities are consistent with known gender-related changes in pituitary growth hormone secretion in aging animals. AB - The effect of aging on hepatic drug conjugation in 5- to 6-, 12- to 13- and 22- to 23-month-old female Fischer 344 rats was examined. The overall disposition of acetaminophen including the formation and elimination kinetics of its sulfate and glucuronide metabolites were used as in vivo probes. The effects of aging on selected in vitro drug metabolizing enzyme activities and on the pattern of phenol and bile salt sulfotransferase isoenzymes were also determined. Aging decreased the total clearance of acetaminophen and the partial clearance of acetaminophen to acetaminophen sulfate by 36 and 47%, respectively. Increasing age also resulted in a reduced partial clearance of acetaminophen to the glucuronide- (24%) and to the glutathione-derived conjugates (29%). UDP glucuronosyltransferase activity toward 1-naphthol, morphine and testosterone was unaffected by advanced age, whereas there was a significant correlation between increased age and increased UDP glucuronosyltransferase activity toward estrone. Cytochrome P-450 concentration and glutathione-S-transferase activity toward 1 chloro-2,4-dinitrobenzene were unchanged by aging. Oxidative demethylase activity toward p-nitroanisole was decreased 18% and sulfotransferase activities toward p nitrophenol, acetaminophen and glycolithocholate were decreased 27, 12 and 12%, respectively, in the 22- to 23-month-old rats, compared to the 5- to 6-month-old animals. In contrast to the age-related feminization in the pattern of sulfotransferase isoenzyme activities that occurs in male rats, there was no effect of aging on the pattern of phenol and bile salt sulfotransferase isoenzyme activities in female rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243344 TI - Functional studies of nonpeptide angiotensin II receptor subtype-specific ligands: DuP 753 (AII-1) and PD123177 (AII-2). AB - DuP 753 and PD123177 are two nonpeptide angiotensin II (AII)-specific ligands, which show high affinities for two respective and distinct subtypes of AII binding sites, i.e., AII-1 and AII-2 sites, respectively, in the rat adrenal gland, brain and uterus. The objective of this study is to identify the functions of these subtype binding sites in the adrenal, sympathetic ganglia, brain and vascular smooth muscle. In conscious rats, DuP 753 at 1, 3 and 10 mg/kg i.v. but not PD123177 at 30 and 100 mg/kg i.v. inhibited the AII-induced aldosterone increase. In the isolated perfused rat adrenal gland, DuP 753 at 10(-6) and 10( 4) M but not PD123177 at 10(-3) M blocked the AII-induced epinephrine secretion. In control and chemically sympathectomized pithed rats, the pressor and tachycardiac responses to AII were blocked by DuP 753 at 10 mg/kg i.v. but not by PD123177 at 100 mg/kg i.v. In conscious rats, DuP 753 at 10 mg/kg s.c. but not PD123177 at 100 mg/kg s.c. inhibited the AII-induced water drinking. In the rabbit aorta, DuP 753 at 10(-6) M but not PD123177 at 10(-4) M inhibited the contractile effect of AII. In conscious renal artery-ligated hypertensive rats, DuP 753 but not PD123177 at 0.1 to 10 mg/kg i.v. lowered blood pressure. In summary, a function of the PD123177-sensitive AII binding site (AII-2) has not yet been identified. However, the DuP 753-sensitive site (AII-1) appears to mediate the AII-induced responses such as adrenal aldosterone and catecholamine secretion, release of catecholamine from sympathetic ganglia, drinking and vasoconstriction. PMID- 2243345 TI - Dipyridamole inhibition of HCO3(-)-Cl- exchange in human erythrocytes. AB - Effects of dipyridamole (DP) on Band 3-mediated HCO3(-)-Cl- exchange were investigated in human red cells at 37 degrees C. The kinetics of net HCO3(-)-Cl- exchange were monitored using a stopped-flow rapid reaction apparatus, under conditions in which HCO3(-)-Cl- exchange was rate-limiting for pH equilibration across the red cell membrane. DP was found to be a rapidly acting, potent inhibitor of HCO3(-)-Cl- exchange, with an apparent I50 of 4 microM. DP produced a mixed competitive-noncompetitive inhibition of HCO3-Cl- exchange. Greater than 50% of the inhibitory effect occurred within 20 msec of DP-red cell interaction, consistent with DP binding to an outward-facing site on the cell membrane. Interaction of red cells with DP was associated with a pH-dependent decrement in the equilibrium Donnan H+ ratio. Because HCO3(-)-Cl- exchange is crucial in vivo for ensuing rapid pH equilibration across the red cell membrane, these effects of DP may have important implications, particularly in the development of high-dose DP regimes for use as an adjunctive agent in cancer chemotherapy. PMID- 2243346 TI - Evidence that peptidoleukotriene is a prerequisite for antigen-dependent thromboxane synthesis in IgG1-passively sensitized guinea pig lungs. AB - Lungs from guinea pigs passively sensitized with an affinity-purified IgG1 antibody produce both leukotriene (LT)D4 and thromboxane (Tx)B2 upon ex vivo antigen challenge. This study was undertaken to determine the possibility of endogenously generated peptido-LTs being a prerequisite for Tx synthesis. In immunoglobulin G1-sensitized lungs, exogenous LTD4 induced TxB2 production with a median effective dose of 4.1 nM, whereas the response to LTE4, LTB4 or platelet activating factor was relatively weak. Although LTC4 was as potent as LTD4 in stimulating TxB2 generation, LTC4's dose-response curve was shifted significantly to the right by AT-125, an irreversible gamma-glutamyl transpeptidase inhibitor, suggesting that at least a part of LTC4 sensitized lungs with antigen (0.01-30 micrograms/ml ovalbumin) for 20 min precipitated a significant amount of LTD4 production. The levels of LTD4 range from 8 to 26 nM (without taking LTD4 recovery into consideration). This level is 2- to 7-fold greater than the median effective dose value observed with exogenous LTD4. Moreover, pretreatment of sensitized lungs with ICI-198,615 a specific LTD4 antagonist, blocked equally both antigen (IC50 = 0.01 microM)- and LTD4 (IC50 = 0.017 microM)-induced TxB2 production. When sensitized lung fragments were treated with 5 mM AT-125, ICI 198,615 was effective in preventing not only antigen-but also LTC4-dependent production of TxB2 (IC50 = 0.018 and 0.021 microM, respectively). In contrast, neither WEB-2086, a platelet-activating factor antagonist, nor pyrilamine, a histamine antagonist, inhibited antigen and LTD4 responses (IC50 greater than 30 microM). Unlike its effect on antigen response, ICI-198,615 was unable to block Ca2+ ionophore-induced TxB2 production.2 PMID- 2243347 TI - Stable circadian mechanisms of toxicity of two platinum analogs (cisplatin and carboplatin) despite repeated dosages in mice. AB - The toxicities and tissue uptake of cisplatin (CDDP) and carboplatin (CBDCA) vary largely according to the time of injection of a single dose. Repeated dosages may alter the mechanisms involved with such circadian-dependent toxicity. Weekly i.v. injections of CDDP (5 mg/kg) or CBDCA (50 mg/kg) were given over 2 months to 288 male B6D2F1 mice standardized by an alternation of 12 hr of light and 12 hr of darkness at any one of three circadian dosing times (0, 8 or 16 hr after light onset--HALO). Survival; body weight; complete blood cell counts; histologic lesions in kidney, liver, spleen, bone marrow and intestinal tract; platinum concentration in kidney, spleen and colon were determined every 2 weeks throughout treatment. Thrombocytopenia was 10-fold larger following CBDCA as compared with CDDP. Severe bone marrow necrosis was cumulative following CDDP, but reversible following CBDCA. Leukopenia and bone marrow lesions were, respectively, half as severe following the dosing of either drug at 16 HALO compared with 0 or 8 HALO. Cortical tubular necrosis was observed in CDDP-treated mice. It was cumulative and half as extensive after drug dosing at 16 HALO, as compared with 0 or 8 HALO (P less than or equal to .05). Total Pt accumulation in all three tissues was 3- to 4-fold higher following repeated dosages of CDDP as compared with CBDCA. Tissue Pt uptake was halved after CDDP or CBDCA dosing at 16 HALO as compared with 8 HALO (P less than or equal to .01). Dosing either Pt complex at the appropriate time is even more critical if administrations are to be repeated. Mechanisms appear to involve the circadian rhythm-dependent ability of target tissues to take up the drug. PMID- 2243348 TI - Both d-cis- and l-cis-diltiazem have anti-ischemic action in the isolated, perfused working rat heart. AB - The effect of diltiazem (d-cis-diltiazem) on the ischemic myocardium was compared with that of l-cis-diltiazem, an optical isomer having less potent calcium channel-blocking action, in the isolated, perfused working rat heart. Ischemia decreased mechanical function and tissue levels of ATP and creatine phosphate, and increased tissue levels of nonesterified fatty acids (NEFA), AMP and lactate. Reperfusion did not restore mechanical function, but restored incompletely the levels of metabolites (except NEFA) that had been altered by ischemia. The ischemia-induced changes in NEFA were prevented by d-cis-diltiazem completely and by l-cis-diltiazem incompletely. Other metabolic changes induced by ischemia were attenuated by d-cis-diltiazem but not by l-cis-diltiazem. In heart pretreated with d-cis- or l-cis-diltiazem, both the mechanical function and the levels of metabolites recovered during reperfusion, the degree of recovery with both drugs being similar. These results indicate that not only d-cis-diltiazem but also l cis-diltiazem has an anti-ischemic action probably due to inhibition of the tissue NEFA accumulation. These results also suggest that the mechanism of the protective effect of d-cis-diltiazem on the ischemic myocardium is not entirely due to the calcium channel-blocking action. Treatment with low Ca2+ (1.0 mM CaCl2) also attenuated the ischemia-induced changes. The interval between reoxygenation and start of function in the reperfused heart that had been treated with low Ca2+ was significantly longer than that with d-cis- or l-cis-diltiazem. The effect of these isomers to shorten this interval may contribute to their common anti-ischemic action. PMID- 2243349 TI - Influence of chronic alcohol administration on representative indices of puberty and sexual maturation in male rats and the development of their progeny. AB - The effects of chronic alcohol administration on reproductive endocrinology in the developing male rat were examined. Prepubescent male rats (25 days of age) were maintained on an alcohol liquid diet or were pair-fed a control diet until early adulthood and selected indices of sexual maturation were examined at weekly intervals. To determine whether sexually immature animals were more sensitive to the effects of alcohol than adults, fully mature male animals were exposed to an identical period of alcohol exposure and comparisons were made between the two groups. The results demonstrated that alcohol significantly affected many of the primary indices of puberty and sexual maturation. The normal pubertal increases in serum testosterone levels, the weights of the testes and secondary sex organs and beta-endorphin levels in the hypothalamus were substantially reduced in alcohol-exposed animals compared with controls. In contrast to these results, the effects of alcohol on reproductive endocrinology in the fully mature animal were transitory and of considerably less magnitude. After a 2-week alcohol-free period, male rats exposed to alcohol during development were bred with drug-naive primiparous females. Although the same number of pregnancies resulted from matings between alcohol-exposed males and drug-naive females compared with controls, litter sizes were significantly smaller in alcohol-derived offspring than in controls. In all other respects, such as body weights, sex ratios, mortality rates and gross developmental features (eye opening, incisor eruption and testes descent), alcohol-derived offspring were identical with controls. Upon closer examination, however, significant disturbances were detected in alcohol derived male offspring.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243350 TI - Acute opioid physical dependence in humans: effect of varying the morphine naloxone interval II. AB - Previous studies have demonstrated antagonist-precipitated withdrawal from 45 min to 24 hr after acute opioid administration in nondependent human subjects. The purpose of this study was to examine longer postagonist intervals and to determine the maximum interval between agonist administration and antagonist challenge at which precipitated withdrawal can be observed. During this study 6 nondependent male volunteers who reported using opiates an average of 4 times per week received naloxone challenges (10 mg/70 kg i.m.) at 6, 12, 24, 36, 48, 60, or 72 hr after single i.m. injections of morphine (18 mg/70 kg or 30 mg/70 kg). Each interval was tested independently in random order. Naloxone reliably precipitated withdrawal signs and symptoms at 6 and 12 hr postmorphine. Withdrawal symptoms were greatly diminished in intensity at 24-hr postmorphine and were not elicited at postmorphine intervals longer than 24 hr. Withdrawal precipitation persisted somewhat longer than pupillary constriction because pupils had returned to predrug diameters by 24 hr postmorphine but, generally, there appeared to be correspondence between offset of agonist effects and dissipation of precipitated withdrawal. This study extends observations about the time course of acute physical dependence effects which begin within minutes after acute morphine exposure, dissipate within 36 hr, are associated with the onset and offset of agonist effects and do not require chronic opioid administration. PMID- 2243351 TI - Augmentation of morphine-induced changes in brain monoamine metabolism after chronic naltrexone treatment. AB - To investigate the role of opioid mechanisms in the regulation of cerebral monoaminergic neurons, male Wistar rats were continuously infused with naltrexone via an Alzet osmotic minipump, or were sham-implanted, for 14 days. Twenty-four hours after removal of the pumps or sham implants, the rats were given s.c. morphine (3, 10 or 30 mg/kg) or saline and were sacrificed 2 hr postinjection. Eight brain regions were assayed for dopamine, 5-hydroxytryptamine, noradrenaline and their respective metabolites. Chronic naltrexone treatment per se caused only small changes in cerebral monoamines. Morphine elevated dose-dependently the cerebral concentrations of the acidic dopamine metabolites, 3,4 dihydroxyphenylacetic acid and homovanillic acid, as well as that of the 5 hydroxytryptamine metabolite, 5-hydroxyindoleacetic acid, and that of the noradrenaline metabolite, free 3-methoxy-4-hydroxyphenylethyleneglycol. In naltrexone-pretreated rats these elevations were significantly larger. Furthermore, in the naltrexone-pretreated rats 10 mg/kg of morphine significantly decreased the concentration of the dopamine metabolite 3-methoxytyramine both in the striatum and in the limbic forebrain, whereas in the control rats the 3 methoxytyramine content fell first after the 30-mg/kg dose and only in the striatum. Thus, both the stimulatory and the inhibitory effects of morphine on cerebral monoaminergic neurons seem to be potentiated by chronic naltrexone treatment. These data suggest that the activity of cerebral monoaminergic systems is to some degree regulated by an endogenous opioid input. When that input is chronically blocked, the basal metabolism of monoamines is not much altered but the systems' responsiveness to agonist challenge is increased. PMID- 2243352 TI - Fate of tritiated 6-fluorodopamine in rats: a false neurotransmitter for positron emission tomographic imaging of sympathetic innervation and function. AB - In evaluating positron-emitting analogs of dopamine (DA) as imaging agents for visualizing tissue sympathetic innervation and function, we assessed the metabolic fate of systemically injected [3H]-6-fluorodopamine [( 3H]-6F-DA) in plasma, in sympathetically innervated tissues (left ventricle, spleen and salivary glands) and in excretory organs (liver and kidney) of rats. By 5 min after intravenous bolus injection of a physiologically inactive amount (450 ng, 10 microCi) of [3H]-6F-DA, 3H was concentrated in all the organs compared with that in blood or plasma. In the sympathetically innervated organs, most of the radioactivity was in [3H]-6F-DA and [3H]-6-fluoronorepinephrine [( 3H]-6F-NE), whereas in the blood, plasma and excretory organs most of the radioactivity was in noncatechol compounds such as O-methylated and conjugated metabolites. In sympathetically innervated organs, tissue/blood ratios exceeded 1.0 at all time points between 5 and 120 min after injection of [3H]-6F-DA and increased progressively (from 8 to 60 in myocardium), whereas the tissue/blood ratios in the kidney and liver increased by less than 2-fold during this interval. In all the studied tissues, the proportion of total tissue 3H that was due to [3H]F-NE increased progressively while that due to [3H]F-DA declined, consistent with conversion of [3H]F-DA to [3H]F-NE in vesicles in sympathetic nerve endings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243353 TI - Autoradiographic characterization of (+-)-1-(2,5-dimethoxy-4-[125I] iodophenyl)-2 aminopropane ([125I]DOI) binding to 5-HT2 and 5-HT1c receptors in rat brain. AB - The 5-HT2 (serotonin) receptor has traditionally been labeled with antagonist radioligands such as [3H]ketanserin and [3H]spiperone, which label both agonist high-affinity (guanyl nucleotide-sensitive) and agonist low-affinity (guanyl nucleotide-insensitive) states of this receptor. The hallucinogen 1-(2,5 dimethoxy-4-iodophenyl)-2-aminopropane (DOI) is an agonist which labels the high affinity guanyl nucleotide-sensitive state of brain 5-HT2 receptors selectively. In the present study, conditions for autoradiographic visualization of (+/-) [125I]DOI-labeled 5-HT2 receptors were optimized and binding to slide-mounted sections was characterized with respect to pharmacology, guanyl nucleotide sensitivity and anatomical distribution. In slide-mounted rat brain sections (+/ )-[125I]DOI binding was saturable, of high affinity (KD approximately 4 nM) and displayed a pharmacologic profile typical of 5-HT2 receptors. Consistent with coupling of 5-HT2 receptors in the high-affinity state to a guanyl nucleotide regulatory protein, [125I]DOI binding was inhibited by guanyl nucleotides but not by adenosine triphosphate. Patterns of autoradiographic distribution of [125I]DOI binding to 5-HT2 receptors were similar to those seen with [3H]ketanserin- and [125I]-lysergic acid diethylamide-labeled 5-HT2 receptors. However, the density of 5-HT2 receptors labeled by the agonist [125I]DOI was markedly lower (30-50%) than that labeled by the antagonist [3H]ketanserin. High densities of [125I]DOI labeling were present in olfactory bulb, anterior regions of cerebral cortex (layer IV), claustrum, caudate putamen, globus pallidus, ventral pallidum, islands of Calleja, mammillary nuclei and inferior olive. Binding in hippocampus, thalamus and hypothalamus was generally sparse. Of note, choroid plexus, a site rich in 5-HT1c receptors had a high density of [125I]DOI binding sites but [3H]ketanserin binding in this region was low. Studies in which [125I]DOI binding to 5-HT2 receptors was blocked with spiperone revealed persisting robust [125I]DOI binding in choroid plexus, which was guanyl nucleotide-sensitive and displayed a pharmacologic profile consistent with its binding to 5-HT1c receptors. These studies suggest that [125I]DOI may be useful as a radiolabel for visualizing the agonist high-affinity state of 5-HT2 receptors and for visualizing 5-HT1c receptors. PMID- 2243354 TI - Protection against gentamicin-induced early renal alterations (phospholipidosis and increased DNA synthesis) by coadministration of poly-L-aspartic acid. AB - Coadministration of polyaspartic acid protects against functional and pathological signs of gentamicin-induced nephrotoxicity in rats without reduction of drug accumulation in renal cortex (Williams et al., J. Pharmacol. Exp. Ther. 237: 919-925, 1986; Gilbert et al., J. Infect. Dis. 159: 945-953, 1989). We have assessed the influence of polyaspartic acid on the early alterations induced in kidney cortex by gentamicin, namely the lysosomal phospholipidosis and the increase in cell turnover. We used an infused rat model in which animals received a total dose of 100 mg/kg of gentamicin over 12 hr. Renal cortex was examined 2 hr (day 0) and 48 hr (day 2) after treatment. All animals received an injection of [3H]thymidine (200 microCi i.p.) before sacrifice. Coadministration of polyaspartic acid (drug-polypeptide mass ratio 1:2.5) did not modify the drug serum levels, as recorded during or shortly after the infusion. Yet, it was associated with 1) an increased (approximately 35%) drug cortical content at day 0; 2) a significant protection against both biochemical (decrease of sphingomyelinase activity at day 0; increase of lipid phosphorus content at day 2) and morphological (enlargement of lysosomes and deposition of myeloid bodies at day 2) signs of lysosomal phospholipidosis in proximal tubular cells; and 3) an almost complete protection against increased cell turnover (mostly in proximal tubules) in cortex at day 2, as assessed by the measurement of [3H]thymidine incorporation into DNA and the enumeration of S-phase cells after histoautoradiography. In addition, morphological studies revealed a larger number of apical vacuoles in proximal tubular cells of animals receiving polyaspartic acid alone (but not in combination with gentamicin), and the deposition of osmiophilic, homogenous material in the lysosomes of animals receiving the combination of gentamicin and polyaspartic acid. Together with the results reported in two companion papers (Kishore et al., J. Pharmacol. Exp. Ther. 867 874, and 875-885, 1990), these results provide evidence that protection afforded by polyaspartic acid extends to the earliest cellular alterations described in kidney for gentamicin, namely the lysosomal phospholipidosis, suggesting that this protecting agent exerts blocking effect from this step in the cascade of events relating drug cortical accumulation to renal toxicity. PMID- 2243355 TI - Mechanism of protection afforded by polyaspartic acid against gentamicin-induced phospholipidosis. I. Polyaspartic acid binds gentamicin and displaces it from negatively charged phospholipid layers in vitro. AB - Coadministration of polyaspartic acid protects rats against aminoglycoside induced nephrotoxicity, with respect to functional and pathological changes as well as to early signs of renal alterations (lysosomal phospholipidosis of proximal tubular cells, increased proliferation of proximal tubular and peritubular cells), without reduction, but actually by increasing the drug cortical content (Williams et al., J. Pharmacol. Exp. Ther. 237: 919, 1986; Gilbert et al., J. Infect. Dis. 159: 945, 1989; Beauchamp et al., 1990). Because aminoglycoside accumulation in kidney cortex involves their segregation in lysosomes, we have examined the possibility of formation of intracellular aminoglycoside-polyaspartic acid complexes that would render the drug less toxic. We found that in vitro polyaspartic acid (MW 9-15,000) 1) binds gentamicin with an optimum at acidic pH (5.4), 2) displaces it from negatively charged liposomes and 3) restores the activity of gentamicin-inhibited lysosomal phospholipase A1 toward phosphatidylcholine included in negatively charged liposomes. In parallel, we also observed that at pH 7.0, polyaspartic acid binds and displaces gentamicin from purified brush-border membrane vesicles, causing an apparent decrease of affinity of gentamicin for these membranes, which was falsely interpreted by Williams et al., J. Pharmacol. Exp. Ther. 237: 919, 1986 as "competition for a common membrane binding site." Assuming that, after its administration in vivo, polyaspartic acid gains access to lysosomes of proximal tubular cells, as many low molecular weight proteins and polypeptides do, our results suggest that protection against gentamicin-induced nephrotoxicity is obtained by the binding of the aminoglycoside to the polyanion in lysosomes, preventing thereby the development of phospholipidosis and therefore interfering with the cascade of events leading from drug accumulation to nephrotoxicity. PMID- 2243356 TI - Evaluation of cationized rat albumin as a potential blood-brain barrier drug transport vector. AB - The present investigations evaluated the effects in rats of repetitive administration of cationized rat albumin over an 8-week period with the future aim of using this modified protein as a vector to transport drugs across the brain capillary endothelial wall, i.e., the blood-brain barrier. Rat albumin was cationized at pH = 7.8 with hexamethylenediamine, and the isoelectric point of the protein was raised from 5.5 to approximately 8. The cationized protein was monomeric based on mobility during sodium dodecylsulfate polyacrylamide gel electrophoresis. After radiolabeling, the cationized rat serum albumin (RSA) was taken up by isolated rat or bovine brain microvessels, whereas radio-labeled native RSA was not taken up by the capillaries in vitro. The brain volume of distribution of the 3H-cationized RSA increased linearly over a 5-hr period after an intravenous injection of the isotope and reached a value of 46 +/- 3 microliter/g (mean +/- S.E.) by 5 hr, whereas the brain volume of distribution of the 125I-native RSA was constant during the 5-hr time period (9.3 +/- 0.7 microliter/g, which is equal to the brain blood volume). The cationized and native RSAs were administered daily (Monday through Friday) at a dose of 1 mg/kg subcutaneously to groups of rats for 4- and 8-week periods. This dosage regimen resulted in no discernible toxicity, based on the findings of normal weight gain, normal tissue histology and normal serum chemistry. Therefore, cationized rat albumin may be used in future studies that use the repetitive administration of cationized rat albumin chimeric peptides for the evaluation of the transport of these substances through the blood-brain barrier in vivo. PMID- 2243357 TI - Prevention of hippocampus neuronal damage in ischemic gerbils by a novel lipid peroxidation inhibitor (quinazoline derivative). AB - We investigated the effect of a novel quinazoline derivative (KB-5666), a lipid peroxidation inhibitor, on ischemic neuronal damage using Mongolian gerbils. The animals were sacrificed 7 or 30 days after 5 min of forebrain ischemia induced by bilateral common carotid artery occlusion. Morphologic changes, a microtubule associated protein 2 (MAP2) immunohistochemical study and quantitative autoradiographic study using [3H]phorbol 12, 13-dibutyrate ([3H]PDBu) were evaluated in the hippocampus after ischemia. KB-5666 (3-50 mg/kg, i.v.) showed protective effects against neuronal death of the CA1 subfield 5 min before ischemia, immediately or 1 hr after ischemia, but not 4 hr after ischemia. KB 5666 (i.p.) also showed protective effects in a dose-dependent manner immediately after ischemia. Furthermore, KB-5666 dose-dependently prevented a marked decrease in microtubule-associated protein 2 immunoreactivity in the dendritic fields of the CA1 pyramidal cells after ischemia. The [3H]PDBu binding activity in the stratum oriens and the stratum lacunosum-moleculare of the CA1 subfield was reduced by 19 and 30%, respectively, 7 days after ischemia. [3H]PDBu binding sites were unchanged in the stratum oriens in the CA3 subfield. By contrast, in the molecular layer of the dentate gyrus, the [3H]PDBu binding activity increased by 15%. KB-5666 (i.v.) prevented a decrease in the [3H]PDBu binding activity in the stratum oriens and stratum lacunosum-moleculare of the CA1 subfield and an increase in the molecular layer of the dentate gyrus. These histologic, immunohistochemical and receptor-autoradiographic data indicate that KB-5666 protects the brain from both cellular and functional consequences of ischemia. PMID- 2243358 TI - Levodopa delivery from controlled-release polymer matrix: delivery of more than 600 days in vitro and 225 days of elevated plasma levels after subcutaneous implantation in rats. AB - Parkinson's disease is commonly treated with orally applied levodopa (l-dopa). However, because this treatment modality is associated with a number of undesirable side effects, some due to plasma fluctuations, we have developed a slow-release polymer system that can be used to deliver l-dopa continuously for extended periods of time in vitro (greater than 600 days) and in vivo (at least 225 days) in rats. In vitro l-dopa release was evaluated using polymer matrices with appropriately selected parameters (loading and geometry), and zero-order (linear) release of l-dopa was observed for more than 600 days (in highly loaded, noncoated material first-order kinetics), in some instances in mg quantities per day. This was achieved even in polymer matrices, which did not possess a dissolution limiting barrier. Scanning electron-microscopic analysis suggests that the mechanism of release is dissolution through channels and pores within the polymer matrix. To assess in vivo release, l-dopa was quantified in plasma from rats given s.c. implants of l-dopa polymer matrices using high-performance liquid chromatography. We observed release of l-dopa for a period of at least 225 days after an initial burst of release. Continuous release of l-dopa from s.c. implanted slow-release polymer matrices has several advantages over oral delivery: 1) l-dopa plasma fluctuations are eliminated, 2) patient compliance issues are reduced and 3) the gastrointestinal tract is circumvented, thus requiring a lower dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243359 TI - Resiniferatoxin: an ultrapotent selective modulator of capsaicin-sensitive primary afferent neurons. AB - Resiniferatoxin (RTX) has been shown to function as an ultrapotent analog of capsaicin. It is reported here that RTX, like capsaicin, acts selectively on primary sensory neurons in rats to produce ultrastructural alterations and calcitonin gene-related peptide depletion. To evaluate RTX actions on capsaicin sensitive nociceptors of vagal origin in the lung, the activation and desensitization of the pulmonary chemoreflex in both rats and cats were examined. In rats, RTX (2 ng-5 micrograms/kg i.v.) failed to elicit the full reflex triad (apnea, systemic hypotension and bradycardia); RTX did, however, desensitize the pulmonary chemosensitive receptors to capsaicin and phenyldiguanide. This effect is not achievable upon acute capsaicin treatment. RTX pretreatment (300 micrograms/kg s.c.) of rats also abolished the neurogenic edema formation, another response mediated via capsaicin-sensitive vagal fibers, in rat trachea to challenge either by capsaicin or ether. The effect of electrical stimulation of vagal nerve was not impaired after RTX injection, indicating that RTX desensitized only the capsaicin-sensitive pathway whereas the parasympathetic pathway remained unaltered. In cats, unlike in the rat, the full pulmonary chemoreflex occurred in response to 0.1 micrograms/kg RTX. It is concluded that RTX is a selective probe for capsaicin-sensitive neural pathways but the spectrum of action of the two compounds is not identical. The failure of RTX to provoke the pulmonary chemoreflex in the rat, which is the main limiting factor in the use of capsaicin, suggests a further advantage to the use of RTX for probing capsaicin-sensitive neural pathways. PMID- 2243360 TI - Analysing and sorting human chromosomes. AB - Analysing and sorting human chromosomes by flow cytometry is a powerful tool in the hands of the molecular biologist. Because of the large number of chromosomes analysed by flow, typically 10(5) for each sample, estimates of the distribution of DNA throughout the chromosome complement of an individual can be made to within three megabase pairs. Rearrangements of DNA in this size range can often be clearly seen and measured by flow cytometry in situations where it was not obvious by traditional cytogenetics. The production of enriched samples of a particular chromosome by flow sorting and the subsequent construction of DNA libraries has played an important part in mapping genes to particular hereditary diseases. Techniques now exist which allow the hybridization of a few thousand sorted chromosomes with characterized or uncharacterized DNA probes to give relatively quick answers about specific chromosome genes. The process of obtaining a sorted chromosome sample from a growing population of peripheral blood lymphocytes or lymphoblastoid cells is compared with other methods of achieving similar results in molecular biological terms. Advances in flow cytometric techniques, which include slit-scanning and hybridization of DNA probes in suspension, are likely to improve the enrichment quality of specific sorted human chromosomes. PMID- 2243361 TI - Flow cytometric evaluation of DNA digestion with micrococcal nuclease on isolated HeLa nuclei. AB - Flow cytometric assessment of DNA digestion with micrococcal nuclease has been performed on isolated HeLa nuclei by determining the relative reduction in stainability with the DNA-specific fluorochrome, propidium iodide. At the nuclease concentrations used, DNA histograms of digested nuclei showed the typical bimodal pattern, when the enzymatic reaction was performed in a medium maintaining chromatin in its native (i.e. condensed) or partially decondensed from. In contrast, when nuclei were digested in a buffer lacking both the mono- and divalent cations K+ and Mg2+, an extensive decrease in fluorescence intensity, with loss of the histogram shape, was observed. In nuclei with native chromatin, DNA stainability decreased as a function of time and enzyme concentration, to reach a lower limit of about 46%, as compared with undigested control samples. Removal of the histone H1 induced a significant increase (approximately by a factor of 2) in the extent of digestion, although only in nuclei with partially decondensed chromatin. These results suggest that the sensitivity of DNA to digestion with micrococcal nuclease can be quantitatively monitored with flow cytometry when appropriate reaction conditions are chosen. PMID- 2243362 TI - Flow cytometric analysis of the functional ability of neutrophils from patients with autoimmune neutropenia. AB - Flow cytometry has been used to evaluate the functional ability of neutrophils and the expression of IgG Fc receptors (FcRII and FcRIII) in autoimmune neutropenia. Quantification of the neutrophil oxidative burst was made by assaying the production of 2'7'-dichlorofluorescein (DCF) from non-fluorescent 2'7'-dichlorofluorescein trapped within the cell, by flow cytometric analysis of cellular fluorescence. In the present study the DCF assay was used to examine the response of neutrophils to stimulation by opsonized and non-opsonized Staphylococcus aureus. In addition, the rate of uptake of S. aureus labelled with the red nuclear dye propidium iodide was determined. The presence of surface bound immunoglobulin, which may affect the phagocytic capacity of the neutrophil, was also measured. No correlation between the neutrophil count and level of membrane-bound IgG or the rate of bacterial uptake was found. The studies were performed on twenty patients with autoimmune neutropenia, twelve with other autoimmune disorders and fourteen normal controls. The rate of uptake of bacteria was considered in relation to the expression of FcRII and FcRIII. Good correlation was found with the level of expression of FcRII, the major receptor for neutrophil activation, and the rate of uptake of bacteria (r = 0.64). PMID- 2243363 TI - x-y-recording in transmission electron microscopy. A versatile and inexpensive interface to personal computers with application to stereology. AB - An interface for IBM XT/AT-compatible computers is described which has been designed to read the actual specimen stage position of electron microscopes. The complete system consists of (i) optical incremental encoders attached to the x- and y-stage drivers of the microscope, (ii) two keypads for operator input, (iii) an interface card fitted to the bus of the personal computer, (iv) a standard configuration IBM XT (or compatible) personal computer optionally equipped with a (v) HP Graphic Language controllable colour plotter. The small size of the encoders and their connection to the stage drivers by simple ribbed belts allows an easy adaptation of the system to most electron microscopes. Operation of the interface card itself is supported by any high-level language available for personal computers. By the modular concept of these languages, the system can be customized to various applications, and no computer expertise is needed for actual operation. The present configuration offers an inexpensive attachment, which covers a wide range of applications from a simple notebook to high resolution (200-nm) mapping of tissue. Since section coordinates can be processed in real-time, stereological estimations can be derived directly "on microscope". This is exemplified by an application in which particle numbers were determined by the disector method. PMID- 2243364 TI - Estimation of surface area and length with the orientator. AB - The orientator is a new technique for the estimation of length and surface density and other stereological parameters using isotropic sections. It is an unbiased, design-based approach to the quantitative study of anisotropic structures such as muscle, myocardium, bone and cartilage. A simple method for the practical generation of such isotropic planes in biological specimens is described. No special technical equipment is necessary. Knowledge of an axis of anisotropy can be exploited to optimize the efficiency. To randomize directions in space, points are selected with uniform probability in a square using various combinations of simple random, stratified random, and systematic random sampling. The point patterns thus produced are mapped onto the surface of a hemisphere. The mapped points define directions of sectional planes in space. The mapping algorithm ensures that these planes are isotropic, hence unbiased estimates of surface and length density can be obtained via the classical stereological formulae. Various implementations of the orientator are outlined: the prototype version, the orientator-generated ortrip, two systematic versions, and the smooth version. Orientator sections can be generated without difficulty in large specimens; we investigated human skeletal muscle, myocardium, placenta, and gut tissue. Slight practical modifications extend the applicability of the method to smaller organs like rat hearts. At the ultrastructural level, a correction procedure for the loss of anisotropic mitochondrial membranes due to oblique orientation relative to the electron beam is suggested. Other potential applications of the orientator in anisotropic structures include the estimation of individual particle surface area with isotropic nucleators, the determination of the connectivity of branching networks with isotropic disectors, and generation of isotropic sections for second-order stereology (three-dimensional pattern analysis). PMID- 2243365 TI - Projection of topographic maps from curved brain surfaces into a plane. AB - The environment is represented in the brain by topographic maps. These maps and their interrelationship form a dominant feature in the brain, but unfortunately, they are often projected onto surfaces which are variously curved. It would be useful to be able to compare the topography on these surfaces quantitatively with the origin of the map. This comparison would be possible if the curved brain surfaces could be represented in planes. Therefore, it was necessary to develop a procedure for unfolding maps on convex structures like the retina and the optic tectum of the chick. For this purpose a unit sphere was constructed whose origin was close to the centre of gravity of the curved brain structure. The surface of this structure was then projected into the sphere. From its representation on the spherical surface it was unfolded into the plane using a polar azimuthal radially equidistant projection. Our method can safely be applied to convex structures only. However, it is not limited to the visual system. The mathematical procedure is formulated in such a way as to be easily implemented. It is exemplified by experiments on the optic tectum and the developing retina of the chick. PMID- 2243366 TI - A direct method for fast three-dimensional serial reconstruction. AB - A method for accurate three-dimensional reconstruction of openly connected porous structures is described. The method is based on embedding of a specimen in a contrast coloured epoxy resin and serial sectioning in a standard hard tissue microtome. A PC-based image processing system is used for direct digitization of the cut surface, and by thresholding two-phase images are obtained. The process is fully automated, and about 170 sections can be produced, digitized, dichotomized, and stored per hour. As an example of its applications, the method is used on trabecular bone, which is an anisotropic porous structure. PMID- 2243368 TI - The 17th Annual Meeting of the Japanese Society of Toxicological Sciences. June 13-14, 1990, Nagoya, Japan. Proceedings. PMID- 2243369 TI - Distribution of cerebral infarcts on computed tomography. AB - Locations of cerebral infarcts on computed tomography were analyzed on all patients admitted for ischemic stroke or status lacunaris in 1984. Patients who had only one symptomatic infarct, without histories of strokes or transient ischemic attacks, were allocated to group A, the rest made up group B. Group A showed that 47.6% of symptomatic infarcts were lacunes with similar percentages in the following areas: lenticular nucleus (12.7%), internal capsule (12.7%), and subcortical white matter (11.1%). In group A, the cortex (49.2%) was the most common site of infarction, while in group B, it was the subcortical white matter (31.7%). However, if the structures supplied by the basal perforating arteries (basal ganglia, thalami, and internal capsules) were considered as a whole, this area (41.8%) was the most common site for infarcts in group B. Thus, asymptomatic infarcts and those of status lacunaris contributed greatly to the overall distribution of cerebral infarcts. PMID- 2243367 TI - In vitro toxicity test of poisonous mushroom extracts with isolated rat hepatocytes. AB - Effects of poisonous mushroom extracts on isolated rat hepatocytes were studied. Though no significant decrease in the cell viability was observed during the incubation of hepatocytes with the extracts at a concentration of 5% (v/v) of Amanita abrupta, A. gymnopus, and A. virosa caused marked decreases in the intracellular glutathione content in sharp contrast to the extracts of A. volvata and A. flavipes. Comparative toxicity tests were carried out for the effects of the extract of A. abrupta, dl-propargylglycine, and alpha-amanitin. The extract of A. abrupta at a concentration of 1% (v/v) caused a marked decrease in the glycogen content, a noticeable elevation in the phosphorylase alpha activity, and a slight acceleration of lipid peroxidation in the hepatocytes. Although dl propargylglycine decreased the intracellular glutathione content progressively with the incubation time, a significant effect of the chemical on lipid peroxidation and the glycogen content was observed only after prolonged incubation at a concentration of 5 mM. On the other hand, alpha-amanitin exerted a little effect on the hepatocytes at 1 microM. These results have indicated that the intoxication by the extract of A. abrupta on the hepatocytes might not due to independently each component, dl-propargylglycine and alpha-amanitin, but combined effect of these components or unidentified substances. PMID- 2243370 TI - Color stability of composite resins. AB - The color stability of seven visible light-cured and three chemically-cured composite resins was investigated while being subjected to UV light irradiation and storage in an aqueous environment at elevated temperatures. Color shift was evaluated visually and by colorimetric measurements. Significant correlation was found between visual scoring and colorimetric readings. When subjected to UV light, a wide deviation in color change existed from brand to brand in photocured composite resins. The color shift of chemically-cured composite resins was less than but fell within the range of photocured composite resins. When stored in water at elevated temperatures, photocured resins exhibited better color stability than the chemically-cured composite resins. PMID- 2243371 TI - [A modified technique of obturator fabrication for cleft palate infants]. AB - Cleft palate is a commonly observed congenital maxillofacial defect. The first problem to be faced is the interference of feeding. It is a hard challenge for both the parents and the dentist. A cleft palate infant is unable to produce negative pressure in the oral cavity, thus resulting in feeding difficulty. The maxillary obturator resolves feeding problem and induces better maxillary growth patterns before operation. The maxillary obturator should be applied as early as possible to avoid the post surgical problems. The material for traditional obturator is tough and often injures the soft tissue. In order not to interfere with the growth of the dental arch, the border of the obturator must be trimmed regularly, until the retention becomes insufficient. In this paper, a modified technique of obturator fabrication was presented. The new method uses silicone relining material instead of ortho resin, as the packing of the obturator. It has been applied to dozens of patients. After a long follow up and comparison with the traditional method, the advantages of the new design can be summarized as follows: (1) Silicone is softer and does not injure the soft tissue. (2) It does not require the trimming of the border of obturator. (3) It has better retention and comfort for the patients. PMID- 2243372 TI - The effect of pitressin and glypressin in variceal bleeding--a preliminary clinical trial. AB - Effects of hemostatic and various side effects were compared between glypressin and pitressin. Fifty-five episodes of esophageal variceal bleeding in 29 patients were studied. Although the glypressin group included more patients in Pugh's classification C than the pitressin group, the result of hemostasis was not influenced. The effect of hemostasis was evaluated in 24 episodes receiving either glypressin or pitressin. The hemostatic effects of glypressin and pitressin were 6/11, 54.5% and 7/13, 53.8% respectively. Eighteen episodes in six patients, with multiple episodes, were used to observe the effect of these two drugs in the same person. No difference was observed. The number of side effects in the glypressin group and the pitressin group were 5 and 10 respectively. Although the side effects of glypressin might be fewer than those of pitressin, chest pain was observed in patients receiving glypressin treatment. The use of glypressin in the patients with cardiac diseases should be studied further. Glypressin is more convenient in clinical use. However, pitressin doses is easily modified. Both drugs might be selected in the control of variceal bleeding. PMID- 2243373 TI - [Clinical studies of neonatal hyperbilirubinemia treated with blood exchange transfusion]. AB - From April 1984 to November 1989, 194 cases of neonatal hyperbilirubinemia treated with blood exchange transfusions (BET) were studied. The patients included 127 male and 67 female neonates, with an age ranged from 13 hours to 16 days. The most common cause was idiopathic (52.6%), followed by G-6-PD deficiency (23.7%), and sepsis (12.9%). Most of the neonates received BET at the 4th day of birth (23.2%), but there were still 30 cases (15.5%) that received BET after 1 week of age. There were 17 cases (8.8%) with maximum serum bilirubin lower than 20 mg/dl before receiving BET, five of them were LBW infants; 11 cases (5.7%) were greater than 40 mg/dl. The mean of maximum serum bilirubin was 26.9 +/- 7.96 mg/dl. Most of the cases received BET once (145 cases) or twice (33 cases). There were two cases that received up to six BET's. One was G-6-PD deficiency and one idiopathic in etiology. No significant difference of BET frequency between sex or body weight (p greater than 0.05) was found. Newborns with higher serum bilirubin due to G-6-PD deficiency, received more BET (p less than 0.05). No significant differences of the pH value (7.33 +/- 0.08 vs 7.35 +/- 0.10) and bicarbonate values (21.20 +/- 3.99 vs 22.00 +/- 3.83 mM/L) occurred before and after blood exchange transfusion (p greater than 0.1). The serum calcium decreased significantly after BET (3.88 +/- 0.91 vs 3.15 +/- 6.97 mEq/L, p less than 0.05). There were 11 deaths in this series, the mortality rate was 5.7%. Three cases (1.5%) were dead within 6 hours after BET.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243374 TI - [The correlating factors affecting nursing personnel resignation in an university hospital]. AB - Demographic characteristics of 1080 university hospital nursing personnel were studied from January 1979 to December 1987. These characteristics included age, marital status, number of children and educational background. Among them, 457 nurses have resigned, while others remain in service. We evaluated the correlations between resignation and various demographic characteristics and the reasons for resignation. This would provide valuable references for nursing recruitment and hospital administration. Our analysis revealed that the reasons for resignation are in the following order: Transfer to governmental hospital, advanced study, marriage, change of occupation, transfer to teaching, personal problems, medical corps to Saudi-Arabia, family responsibilities, and relocation to other cities. Regarding to demographic characteristics, both educational background and marital status affected the reasons for resignation. The average length of service time for nurses who resigned was 30.0 +/- 29.59 months. There are significant differences among the age, marital status, number of children and educational background. The nurses between the age of 21 and 30 years old, (79%) had the highest rate of resignation (45.64%). Those below the age of 20 had the shortest service time, while those above 30 years old had the longest service time. The married nurses also had a longer service time than the single ones. Those who had children had a longer service time compared to those without children. In view of their educational background, those with a bachelor degree had the shortest service time (16.8 +/- 10.3 months) and the highest rate of resignation (71.1%). Our analysis indicates that professional license and location of residence also affected the reasons for resignation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243375 TI - Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding. AB - The binding of the CD4 receptor by the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein is important for virus entry and cytopathic effect. To investigate the CD4-binding region of the gp120 glycoprotein, we altered gp120 amino acids, excluding cysteines, that are conserved among the primate immunodeficiency viruses utilizing the CD4 receptor. Changes in two hydrophobic regions (Thr-257 in conserved region 2 and Trp-427 in conserved region 4) and two hydrophilic regions (Asp-368 and Glu-370 in conserved region 3 and Asp-457 in conserved region 4) resulted in significant reductions in CD4 binding. For most of the mutations affecting these residues, the observed effects on CD4 binding did not apparently result from global conformational disruption of the gp120 molecule, as assessed by measurements of precursor processing, subunit association, and monoclonal antibody recognition. The two hydrophilic regions exhibit a strong propensity for beta-turn formation, are predicted to act as efficient B-cell epitopes, and are located adjacent to hypervariable, glycosylated regions. This study defines a small number of gp120 residues important for CD4 binding, some of which might constitute attractive targets for immunologic intervention. PMID- 2243376 TI - Characterization of the gag/fusion protein encoded by the defective Duplan retrovirus inducing murine acquired immunodeficiency syndrome. AB - Murine acquired immunodeficiency syndrome is induced by a defective retrovirus. Sequencing of this defective viral genome revealed a long open reading frame which encodes a putative gag/fusion protein, N-MA-p12-CA-NC-COOH, (D. C. Aziz, Z. Hanna, and P. Jolicoeur, Nature (London) 338:505-508, 1989). We raised a specific antibody to the unique p12 domain of this gag fusion precursor, Pr60gag. We found that Pr60gag was indeed encoded by the defective viral genome both in cell-free translation reticulocyte extracts and in infected mouse fibroblasts. Pr60gag was found to be myristylated, phosphorylated, and attached to the cell membrane, like other helper murine leukemia virus (MuLV) gag precursors. Pr60gag was not substantially cleaved within the nonproducer cells and was not released from these cells. However, in the presence of helper MuLV proteins, it formed phenotypically mixed particles. In these particles, Pr60gag was only partially cleaved. In helper MuLV-producing cells harboring the defective virus, a gag related p40 intermediate was generated both intracellularly and extracellularly. In these cells, Pr60gag appeared to behave as a dominant negative mutant, interfering with proper cleavage of helper Pr65gag. Our data indicate that Pr60gag is a major (and possibly the only) gene product of the defective murine acquired immunodeficiency syndrome virus and is likely to harbor some determinants of pathogenicity of this virus. PMID- 2243377 TI - Identification and characterization of a baculovirus occlusion body glycoprotein which resembles spheroidin, an entomopoxvirus protein. AB - A 37-kDa polypeptide specified by Autographa californica nuclear polyhedrosis virus was found to share significant homology with Choristoneura biennis entomopoxyvirus spheroidin protein, which is the major component of entomopoxvirus occlusion bodies. Antibodies raised against spheroidin cross reacted with the 37-kDa protein and confirmed its expression in the late phase of wild-type baculovirus infection. Immunoblot analysis and fluorescence microscopy demonstrated that the protein was associated with purified A. californica nuclear polyhedrosis virus occlusion bodies and was absent in purified virions. Immunofluorescence studies localized the protein to the periphery of occlusion bodies and the internal membranes of cells infected with wild-type baculovirus. The open reading frame encoding this spheroidinlike protein was inserted into a baculovirus expression vector, and recombinant protein was synthesized under control of the polyhedrin promoter. Studies of the recombinant protein demonstrated that it was heterogeneous in molecular mass as a result of N-linked glycosylation. Tunicamycin inhibited carbohydrate addition and yielded proteins of 34 and 33 kDa. PMID- 2243378 TI - Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1. AB - Nucleotide sequences in three hypervariable regions of the human immunodeficiency virus type 1 (HIV-1) env gene were obtained by sequencing provirus present in peripheral blood mononuclear cells of HIV-infected individuals. Single molecules of target sequences were isolated by limiting dilution and amplified in two stages by the polymerase chain reaction, using nested primers. The product was directly sequenced to avoid errors introduced by Taq polymerase during the amplification process. There was extensive variation between sequences from the same individual as well as between sequences from different individuals. Interpatient variability was markedly less in individuals infected from a common source. A high proportion of amino acid substitutions in the hypervariable regions altered the number and positions of potential N-linked glycosylation sites. Sequences in two hypervariable regions frequently contained short (3- to 15-bp) duplications or deletions, and by amplifying peripheral blood mononuclear cell DNA containing 10(2) or 10(3) proviral molecules and analyzing the product by high-resolution electrophoresis, the total number and abundance of distinct length variants within an individual could be estimated, providing a more comprehensive analysis of the variants present than would be obtained by sequencing alone. Sequences from many individuals showed frequent amino acid substitutions at certain key positions for neutralizing-antibody and cytotoxic T cell recognition in the immunodominant loop. The rates of synonymous and nonsynonymous nucleotide substitution in the region of this and flanking regions indicate that strong positive selection for amino acid change is operating in the generation of antigenic diversity. PMID- 2243379 TI - The upstream factor-binding site is not essential for activation of transcription from the adenovirus major late promoter. AB - An adenovirus major late promoter (MLP) has been constructed with a 4-bp alteration in the sequence which binds the transcription factor known as USF or MLTF. This upstream element has often been considered necessary and sufficient for maximal transcription of the MLP. A duplex oligonucleotide containing the mutant sequence was not capable of binding specific proteins in a band shift assay, nor was it capable of inhibiting such binding by the wild-type sequence. In an in vitro assay, the mutant sequence was incapable of inhibiting transcription from a duplex sequence containing the MLP, whereas the wild-type sequence could. These two pieces of evidence suggest that the sequence is functionally impaired. Surprisingly, a virus containing the mutant MLP had a normal replication phenotype. On more detailed examination however, we show that the mutant viral MLP was deficient in transcription at 9 h postinfection but that the rate of transcription was close to normal by 20 h postinfection. An inverted CAAT box located immediately upstream of the USF-binding element was not previously thought to be of importance to the functioning of the MLP. However, a single point mutation in the CAAT box, placed in the USF mutant background, had a marked effect upon transcription from the MLP. This result suggests that the MLP may exhibit functional redundancy in which either the USF-binding site or the CAAT box can serve as an upstream promoter element. Neither of the mutant viruses displayed any change in the levels of the divergent IVa2 transcription unit, suggesting that the levels of divergent transcription are not determined by competition for limiting transcription factors. PMID- 2243380 TI - Hepatitis B virus transactivator X protein is not tumorigenic in transgenic mice. AB - The hepatitis B virus X protein acts as a transcriptional transactivator in vitro. To elucidate possible biological effects of X protein on liver cells in vivo, we generated four lines of transgenic mice carrying the X gene open reading frame under the control of the human alpha-1-antitrypsin regulatory region. The plasmid construct used to introduce the transgene was shown to encode a 16-kDa X protein with transactivating capability. The expression of X protein was detectable in liver tissue of transgenic animals of three of the lines by immunoblot analysis; levels of expression were highest in the first month after birth of the animals. Over 80 animals from the expressing lines were examined histologically. Most transgenic mice, some of which were observed for up to 2 years, remained normal. However, a few transgenic animals developed mild focal hepatitis, nuclear pleomorphism, focal necrosis, and/or nodular hyperplasia in the liver. Increased mitotic activity of hepatocytes also was observed. We conclude that, at the level of expression achieved in these transgenic mice, the hepatitis B virus transcriptional transactivator X protein alone does not appear to mediate the development of serious liver damage or hepatocellular carcinomas. PMID- 2243381 TI - Generation of hybrid genes and proteins by vaccinia virus-mediated recombination: application to human immunodeficiency virus type 1 env. AB - The ability of poxviruses to undergo intramolecular recombination within tandemly arranged homologous sequences can be used to generate chimeric genes and proteins. Genes containing regions of nucleotide homology will recombine to yield a single sequence composed of portions of both original genes. A recombinant virus containing two genes with a number of conserved regions will yield a population of recombinant viruses containing a spectrum of hybrid sequences derived by recombination between the original genes. This scheme has been used to generate hybrid human immunodeficiency virus type 1 env genes. Recombinant vaccinia viruses that contain two divergent env genes in tandem array have been constructed. In the absence of selective pressure to maintain both genes, recombination between conserved homologous regions in these genes generated a wide range of progeny, each of which expressed a novel variant polypeptide encoded by the newly created hybrid env gene. Poxvirus-mediated recombination may be applied to map type-specific epitopes, to create novel pharmaceuticals such as hybrid interferons, to study receptor-binding or enzyme substrate specificities, or to mimic the antigenic diversity found in numerous pathogens. PMID- 2243382 TI - Human immunodeficiency virus rev protein recognizes a target sequence in rev responsive element RNA within the context of RNA secondary structure. AB - Human immunodeficiency virus type 1 Rev protein modulates the distribution of viral mRNAs from the nucleus to the cytoplasm by interaction with a highly structured viral RNA sequence, the Rev-responsive element (RRE). To identify the minimal functional elements of RRE, we evaluated mutant RREs for Rev binding in vitro and Rev response in vivo in the context of a Gag expression plasmid. The critical functional elements fold into a structure composed of a stem-loop A, formed by the ends of the RRE, joined to a branched stem-loop B/B1/B2, between bases 49 and 113. The 5' 132 nucleotides of RRE, RREDDE, which possessed a similar structure, bound Rev efficiently but were nonfunctional in vivo, implying separate binding and functional domains within the RRE. Excision of stem-loop A reduced Rev binding significantly and abolished the in vivo Rev response. The B2 branch could be removed without severe impairment of binding, but deletions in the B1 branch significantly reduced binding and function. However, deletion of 12 nucleotides, including the 5' strand of stem B, abolished both binding and function, while excision of the 3' strand of stem B only reduced them. Maintenance of the native RRE secondary structure alone was not sufficient for Rev recognition. Many mutations that altered the primary structure of the critical region while preserving the original RNA conformation were Rev responsive. However, mutations that changed a 5'..CACUAUGGG..3' sequence in the B stem, without affecting the overall structure abolished both in vitro Rev binding and the in vivo Rev response. PMID- 2243383 TI - Use of a cell-free system to identify the vaccinia virus L1R gene product as the major late myristylated virion protein M25. AB - A 25-kDa vaccinia virus (VV) virion protein, designated M25, is modified in vivo by covalent addition of myristic acid. The predicted amino acid sequences of all VV open reading frames which have been reported were searched for the sequence M G-X-X-X-(S/T/A), which has been proposed to be the consensus recognition signal for cotranslational modification of proteins by N-myristyltransferase. This conserved signal was found at the amino terminus of a single locus, which corresponded to the leftmost rightward-reading open reading frame (L1R) initiating within the VV HindIII L DNA fragment. By using synthetic oligonucleotides in concert with polymerase chain reaction techniques, a chimeric gene consisting of open reading fram L1R fused to a bacteriophage T7 promoter was constructed and cloned into a plasmid vector. Transcripts derived from the wild type expression plasmid (designated pL1G1) were translated in vitro in a wheat germ extract to yield a polypeptide with an apparent molecular mass of 25 kDa. This polypeptide was labeled with either [35S]methionine or [3H]myristic acid and comigrated with in vivo-labeled protein M25 on sodium dodecyl sulfate polyacrylamide gels. Polyclonal antiserum generated in rabbits against a trpE:L1R fusion protein immunoprecipitated a 25-kDa protein labeled either in vitro (the L1R gene product, designated protein L1) or in vivo (from purified VV, protein M25), identifying the M25 protein as the gene product of open reading frame L1R. Chromatographic analysis of the protein L1-bound fatty acid moieties liberated after acid methanolysis resulted in recovery of greater than 99% of the fatty acid as myristate-associated label. Cell-free translation of proteins derived from a set of deletions from the carboxy terminus of the open reading frame L1R suggested that the site of myristylation maps near the amino terminus of protein L1. This hypothesis was supported by cell-free translation of mutant L1R transcripts in which the penultimate glycine codon had been altered by site directed mutagenesis to encode either an aspartic acid (pL1D1) or alanine (pL1A1) residue. In both cases, the mutant transcripts were translated into a 25-kDa protein which could be labeled in vitro with [35S]methionine but not with [3H]myristic acid. These data demonstrate that VV open reading frame L1R encodes a myristylated protein and provide evidence that the site of modification of protein L1 is the amino-terminal glycine residue. PMID- 2243384 TI - Different sites of interaction for Rev, Tev, and Rex proteins within the Rev responsive element of human immunodeficiency virus type 1. AB - We have analyzed the action of the Rev and Tev proteins of human immunodeficiency virus type 1 (HIV-1) and of the Rex protein of human T-cell leukemia virus type I (HTLV-I) on a series of Rev-responsive element (RRE) mutants. The minimum continuous RRE region necessary and sufficient for Rev function was determined to be 204 nucleotides. Interestingly, this region was not sufficient for Tev or Rex function. These proteins require additional sequences, which may stabilize the structure of the RRE or may contain additional sequence-specific elements. Internal RRE deletions revealed that the targets for Rev and Rex can be separated, since mutants responding to Rev and not Rex and vice versa were identified. Tev was active on both types of mutants, suggesting that it has a more relaxed specificity than do both Rev and Rex proteins. Although Rev and Rex targets within the RRE appear to be distinct, the trans-dominant mutant RevBL prevents the RRE interaction with Rex. RevBL cannot inhibit the function of Rex on RRE deletions that lack the Rev-responsive portion. These results indicate the presence of distinct sites within the RRE for interaction with these proteins. The binding sites for the different proteins do not function independently and may interfere with one another. Mutations affecting the RRE may change the accessibility and binding characteristics of the different binding sites. PMID- 2243385 TI - Structural analysis of wild-type and mutant human immunodeficiency virus type 1 Tat proteins. AB - We expressed the human immunodeficiency virus type 1 transactivator protein, Tat, in the wheat germ cell-free translation system and found it to exist as a monomer. The first coding exon (residues 1 to 72) of wheat germ-expressed Tat was resistant to trypsin digestion, indicating that it is a highly folded, independently structured protein domain. Several mutant Tat proteins were dramatically more sensitive to trypsin than the wild type was, suggesting that their reduced transactivation activities are the result of destabilized structures. Mutant proteins with single-amino-acid substitutions were also identified that had reduced transactivation activities but wild-type structures in the trypsin assay. These mutants clustered in two regions of Tat, at acidic residues 2 and 5 in the amino terminus and between residues 18 and 32. These mutants, wild type in structure but reduced in activity, identify residues in the wild-type protein that may directly contact other molecules during Tat function. PMID- 2243387 TI - Mutational analysis of a vaccinia virus intermediate promoter in vivo and in vitro. AB - The expression of the vaccinia virus intermediate I3 gene depends on trans-acting factors which are present in an active state prior to DNA replication. However, activation of transcription requires DNA replication in cis (J. C. Vos and H. G. Stunnenberg, EMBO J., 7:3487-3492, 1988). We have made deletion and linker scanner mutations of the I3 promoter to determine the sequence requirements for transcriptional activity and the dependence of DNA replication. The I3 promoter appears to consist of two elements which are essential and sufficient for accurate transcription initiation both in vivo and in vitro. An upstream and a downstream sequence element were defined ranging from -20 to -9 and +1 to +9, respectively. The upstream element appears to be highly homologous to a sequence in the intermediate I8 promoter. A 3-bp substitution in the upstream I3 promoter element resulted in a change of transcriptional specificity from intermediate to late. Finally, the mutations did not result in an activation of the intermediate promoter prior to DNA replication. PMID- 2243386 TI - Analysis of efficiently packaged defective interfering RNAs of murine coronavirus: localization of a possible RNA-packaging signal. AB - We have previously shown that most of the defective interfering (DI) RNA of mouse hepatitis virus (MHV) are not packaged into virions. We have now identified, after 21 serial undiluted passages of MHV, a small DI RNA, DIssF, which is efficiently packaged into virions. The DIssF RNA replicated at a high efficiency on its transfection into the helper virus-infected cells. The virus released from the transfected cells interfered strongly with mRNA synthesis and growth of helper virus. cDNA cloning and sequence analysis of DIssF RNA revealed that it is 3.6 kb and consists of sequences derived from five discontinuous regions of the genome of the nondefective virus. The first four regions (domains I to IV) from the 5' end are derived from gene 1, which presumably encodes the RNA polymerase of the nondefective virus. The entire domain I (859 nucleotides) and the first 750 nucleotides of domain II are also present in a previously characterized DI RNA, DIssE, which is not efficiently packaged into virions. Furthermore, the junction between these two domains is identical between the two DI RNAs. The remaining 77 nucleotides at the 3' end of domain II and all of domains III (655 nucleotides) and IV (770 nucleotides) are not present in DIssE RNA. These four domains are derived from gene 1. In contrast, the 3'-most domain (domain V, 447 nucleotides) is derived from the 3' end of the genomic RNA and is also present in DIssE. The comparison of primary sequences and packaging properties between DIsse and DIssF RNAs suggested that domains III and IV and part of the 3' end of domain II contain the packaging signal for MHV RNA. This conclusion was confirmed by inserting these DIssF-unique sequences into a DIssE cDNA construct; the in vitro transcribed RNA from this hybrid construct was efficiently packaged into virion particles. DIssF RNA also contains an open reading frame, which begins from domain I and ends at the 5'-end 20 bases of domain III. In vitro translation of DIssF RNA and metabolic labeling of the virus-infected cells showed that this open reading frame is indeed translated into a 75-kDa protein. The structures of both DIssE and DIssF RNAs suggest that a protein-encoding capability is a common characteristic of MHV DI RNA. PMID- 2243389 TI - Analysis of the role of brome mosaic virus 1a protein domains in RNA replication, using linker insertion mutagenesis. AB - Brome mosaic virus (BMV) belongs to a "superfamily" of plant and animal positive strand RNA viruses that share, among other features, three large domains of conserved sequence in nonstructural proteins involved in RNA replication. Two of these domains reside in the 109-kDa BMV 1a protein. To examine the role of 1a, we used biologically active cDNA clones of BMV RNA1 to construct a series of linker insertion mutants bearing two-codon insertions dispersed throughout the 1a gene. The majority of these mutations blocked BMV RNA replication in protoplasts, indicating that both intervirally conserved domains function in RNA replication. Coinoculation tests with a large number of mutant combinations failed to reveal detectable complementation between mutations in the N- and C-terminal conserved domains, implying that these two domains either function in some directly interdependent fashion or must be present in the same protein. Four widely spaced mutations with temperature-sensitive (ts) defects in RNA replication were identified, including a strongly ts insertion near the nucleotide-binding consensus of the helicaselike C-terminal domain. Temperature shift experiments with this mutant show that 1a protein is required for continued accumulation of all classes of viral RNA (positive strand, negative strand, and subgenomic) and is required for at least the first 10 h of infection. ts mutations were also identified in the 3' noncoding region of RNA1, 5' to conserved sequences previously implicated in cis for replication. Under nonpermissive conditions, the cis-acting partial inhibition of RNA1 accumulation caused by these noncoding mutations was also associated with reduced levels of the other BMV genomic RNAs. Comparison with previous BMV mutant results suggests that RNA replication is more sensitive to reductions in expression of 1a than of 2a, the other BMV-encoded protein involved in replication. PMID- 2243388 TI - Coordinate enhancement of cytokine gene expression in human immunodeficiency virus type 1-infected promonocytic cells. AB - A promonocytic cell model was used to investigate cytokine gene transcription in U937 and U9-IIIB cells chronically infected with human immunodeficiency virus type 1 (HIV-1). The production of interferon (alpha-1 interferon [IFN-alpha 1], IFN-alpha 2, and IFN-beta), interleukin (interleukin 1 alpha [IL-1 alpha], IL-1 beta, and IL-6), and tumor necrosis factor alpha (TNF-alpha) mRNA was characterized by quantitative polymerase chain reaction mRNA phenotyping in U937 and U9-IIIB cells following coinfection with Sendai paramyxovirus or stimulation with lipopolysaccharide (LPS). Chronic HIV-1 infection of U9-IIIB cells resulted in a low constitutive level of transcription of TNF and IL-1 genes but not IFN genes; however, when the cells were coinfected with Sendai virus, 10- to 20-fold higher levels of IFN-beta, IL-1 beta, IL-6, and TNF-alpha mRNA were observed in U9-IIIB cells than in similarly induced U937 cells. The enhanced levels of cytokine RNA in virus-infected U9-IIIB cells were also accompanied by higher levels of IFN antiviral activity and TNF secretion than in U937 cells. Transcript levels for IFN-alpha 1 and IFN-alpha 2 were equivalently induced in virus infected U937 and U9-IIIB cells, indicating that a generalized derepression of cytokine gene expression did not occur as a consequence of HIV-1 infection. When LPS was used as an inducer, a distinct pattern of cytokine gene expression was detected in U9-IIIB cells. TNF-alpha and IL-1 beta but not IFN-alpha or IFN-beta transcripts were induced by LPS. These results suggest that HIV-1 infection of promonocytic cells may prime or sensitize cells such that subsequent antigenic challenge leads to coordinate enhancement of cytokine gene expression. PMID- 2243390 TI - The arginine-rich domain of hepatitis B virus precore and core proteins contains a signal for nuclear transport. AB - Precore and core proteins are two related co-carboxy-terminal proteins of hepatitis B virus. Precore protein contains the entire sequence of core protein plus an amino-terminal extension of 29 amino acid residues. Both proteins can display a common antigenic determinant known as core antigen (HBcAg). Clinically, HBcAg is detected in the nucleus, cytoplasm, or both of hepatitis B virus infected hepatocytes. In order to understand the mechanism that regulates nuclear transport of HBcAg, various portions of precore and core proteins were linked to a reporter protein, human alpha-globin, and expressed in mammalian cells. Our results indicate that the precore protein-specific sequence, although important for nuclear transport, does not contain a nuclear localization signal. Instead, a signal for nuclear transport is located near the carboxy termini of precore and core proteins in the arginine-rich domain. This signal is made up of a set of two direct PRRRRSQS repeats and is highly conserved among mammalian hepadnaviruses. PMID- 2243391 TI - The viral envelope gene is involved in macrophage tropism of a human immunodeficiency virus type 1 strain isolated from brain tissue. AB - Human immunodeficiency virus type 1 (HIV-1) strains isolated from the central nervous system (CNS) may represent a subgroup that displays a host cell tropism different from those isolated from peripheral blood and lymph nodes. One CNS derived isolate, HIV-1SF128A, which can be propagated efficiently in primary macrophage culture but not in any T-cell lines, was molecularly cloned and characterized. Recombinant viruses between HIV-1SF128A and the peripheral blood isolate HIV-1SF2 were generated in order to map the viral gene(s) responsible for the macrophage tropism. The env gene sequences of the two isolates are about 91.1% homologous, with variations scattered mainly in the hypervariable regions of gp120. Recombinant viruses that have acquired the HIV-1SF128A env gene display HIV-1SF128A tropism for macrophages. Furthermore, the gp120 variable domains, V1, V2, V4, and V5, the CD4-binding domain, and the gp41 fusion domain are not directly involved in determining macrophage tropism. PMID- 2243392 TI - A novel mechanism for the initiation of Tacaribe arenavirus genome replication. AB - The ends of arenavirus genome and antigenome RNAs are highly conserved and where determined directly, always contain a 3' G (referred to as position +1). However, primers extended to the 5' ends of Tacaribe virus genomes and antigenomes extend to position -1. When genomes and antigenomes are annealed either inter or intramolecularly and treated with RNase A or T1, there appears to be a single unpaired G at the 5' ends of the hybrids. A single extra G is also found by cloning the 5' ends of S antigenomes, and studies with capping enzyme detect (p)ppG at the 5' ends of genome and antigenome chains. A model is proposed in which genome replication initiates with pppGpC to create the nontemplated extra G. In contrast, the nontemplated bases at the 5' ends of the N mRNAs, which extend to positions -1 to -5, were found to be capped and also heterogeneous in sequence. PMID- 2243393 TI - Monoclonal antibody protection from age-dependent poliomyelitis: implications regarding the pathogenesis of lactate dehydrogenase-elevating virus. AB - Over 90% of cyclophosphamide-treated, 6- to 7-month-old C58/M mice developed fatal paralytic disease after infection with a virulent strain of lactate dehydrogenase-elevating virus (LDV), with a mean onset of paralysis of about 16 days. Passive immunization with polyclonal antibodies or with a group of anti-LDV monoclonal antibodies (MAbs) with single-epitope specificity 1 day before or at the time of LDV infection prevented the development of paralytic disease without interfering with the replication of LDV in permissive macrophages, the primary host cells of LDV. In situ hybridization of spinal cord sections with an LDV specific cDNA probe indicated that the MAb specifically prevented the cytocidal infection of motor neurons by LDV without blocking the infection of smaller nonneuronal cells in the spinal cord. The protective antibodies recognize at least two different epitopes on the glycoprotein of LDV, VP-3. Passive immunizations with other anti-LDV MAbs, which recognize at least three other epitopes on VP-3 of LDV, afforded no protection. In contrast to the protective effect of anti-LDV MAb injection before or at the time of LDV infection, their administration postinfection exerted relatively little protection, though it delayed the appearance of paralytic symptoms. However, repeated injections of MAbs until at least 7 days postinfection also afforded a high degree of protection. The results indicate that protective MAbs may interfere with two stages in the development of LDV-induced paralytic disease. When administered at the time of LDV infection, they prevent the initial infection of spinal cord motor neurons. After this initial event, repeated injections of MAb are required to inhibit the spread of LDV between neurons until the endogenous production of protective anti-LDV antibodies in these mice. PMID- 2243394 TI - Analysis of long terminal repeat circle junctions of human immunodeficiency virus type 1. AB - Circle junctions of unintegrated human immunodeficiency virus type 1 strain IIIB were analyzed after polymerase chain reaction amplification. Among the 28 colonies sequenced, eight unique circle junction species were detected. Five of the eight species resulted in circle junctions with larger inserts than predicted. A majority of these could result from heterogeneity in generating the U5' long terminal repeat terminus. PMID- 2243396 TI - Changes in the transmembrane region of the human immunodeficiency virus type 1 gp41 envelope glycoprotein affect membrane fusion. AB - The charged amino acids near or within the membrane-spanning region of the human immunodeficiency virus type 1 gp41 envelope glycoprotein were altered. Two mutants were defective for syncytium formation and virus replication even though levels of envelope glycoproteins on the cell or virion surface and CD4 binding were comparable to those of the wild-type proteins. Thus, in addition to anchoring the envelope glycoproteins, sequences proximal to the membrane-spanning gp41 region are important for the membrane fusion process. PMID- 2243395 TI - Intracellular interaction of human immunodeficiency virus type 1 (ARV-2) envelope glycoprotein gp160 with CD4 blocks the movement and maturation of CD4 to the plasma membrane. AB - The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) plays a major role in the down-regulation of its receptor, CD4. Using a transient expression system, we investigated the interaction of the HIV-1 envelope glycoprotein with CD4 during their movement through the intracellular membrane traffic. In singly transfected cells, the envelope glyprotein gp160 was synthesized, glycosylated, and localized predominantly in the endoplasmic reticulum. Only a minor fraction of gp160 was proteolytically cleaved, producing gp120 and gp41, and gp120 was secreted into the medium. On the other hand, the CD4 molecule, when expressed alone, was properly glycosylated and transported efficiently to the cell surface. However, when gp160 and CD4 were coexpressed in the same cell, the cell surface delivery of CD4 was greatly reduced. In coexpressing cells, CD4 formed a specific intracellular complex with gp160 as both proteins could be immunoprecipitated by antibodies against either the gp160 or CD4 (OKT4) but not by OKT4A, a blocking antibody against CD4. The specific gp160-CD4 complex was localized predominantly in the endoplasmic reticulum, and the CD4 in the complex did not acquire endoglycosidase H resistance. The present studies demonstrated that a specific intracellular interaction between gp160 and CD4 was responsible for the cell surface down-regulation of CD4 in cells expressing both the envelope glycoprotein of HIV-1 and its receptor, CD4. PMID- 2243397 TI - Parental influenza virion nucleocapsids are efficiently transported into the nuclei of murine cells expressing the nuclear interferon-induced Mx protein. AB - The interferon-induced murine Mx1 protein, which is localized in the nucleus, most likely specifically blocks influenza virus replication by inhibiting nuclear viral mRNA synthesis, including the mRNA synthesis catalyzed by inoculum (parental) virion nucleocapsids (R. M. Krug, M. Shaw, B. Broni, G. Shapiro, and O. Haller, J. Virol. 56:201-206, 1985). We tested two possible mechanisms for this inhibition. First, we determined whether the transport of parental nucleocapsids into the nucleus was inhibited in murine cells expressing the nuclear Mx1 protein. To detect the Mx1 protein, we prepared rabbit antibodies against the Mx1 protein with a CheY-Mx fusion protein expressed in bacteria. The fate of parental nucleocapsids was monitored by immunofluorescence with an appropriate dilution of monoclonal antibody to the nucleocapsid protein. The protein synthesis inhibitor anisomycin was added to the cells 30 min prior to infection, so that the only nucleocapsids protein molecules in the cells were those associated with nucleocapsids of the parental virus. These nucleocapsids were efficiently transported into the nuclei of murine cells expressing the Mx1 protein, indicating that this protein most likely acts after the parental nucleocapsids enter the nucleus. The second possibility was that the murine Mx1 protein might act in the nucleus to inhibit viral mRNA synthesis indirectly via new cap-binding activities that sequestered cellular capped RNAs away from the viral RNA transcriptase. We show that the same array of nuclear cap-binding proteins was present in Mx-positive and Mx-negative cells treated with interferon. Interestingly, a large amount of a 43-kDa cap-binding activity appeared after interferon treatment of both Mx-positive and Mx-negative cells. Hence, the appearance of new cap-binding activities was unlikely to account for the Mx-specific inhibition of viral mRNA synthesis. These results are most consistent with the possibility that the Mx1 protein acts directly to inhibit the viral transcriptase in the nucleus. PMID- 2243398 TI - CD4-independent infection by human immunodeficiency virus type 1 after phenotypic mixing with human T-cell leukemia viruses. AB - Although human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome and related disorders, it has been suggested that viral cofactors may accelerate the progression of the disease. We present evidence that human T lymphoid cells productively coinfected by HIV type 1 (HIV 1) and human T-cell leukemia virus type I (HTLV-I) or HTLV-II generate a progeny of phenotypically mixed viral particles that allow the penetration of HIV-1 into previously nonsusceptible CD4- human cells, including mature CD8+ T lymphocytes, B lymphoid cells, epithelial cells, and skeletal muscle cells. The infection is independent of the major HIV-1 receptor, (i.e., the CD4 glycoprotein) since OKT4a, a neutralizing anti-CD4 monoclonal antibody, fails to block the penetration of HIV-1. Similarly, infection is not inhibited by monoclonal antibody M77, directed toward the neutralizing loop of the gp120 envelope glycoprotein of HIV-1. In contrast, pretreatment of the virus stock with HTLV-I neutralizing human serum completely abolishes the penetration of phenotypically mixed HIV-1 into CD4- cells. These results suggest that HTLV-I or HTLV-II may increase the pathogenicity of HIV-1 by broadening the spectrum of its cellular tropism and, thus, favoring its spread within the organism of coinfected hosts. PMID- 2243399 TI - Strains from both Theiler's virus subgroups encode a determinant for demyelination. AB - The GDVII strain and other members of the GDVII subgroup of Theiler's murine encephalomyelitis viruses (TMEV) cause an acute lethal neuronal infection in mice, whereas the DA strain and other members of the TO subgroup of TMEV cause a chronic demyelinating disease associated with a persistent virus infection. We used GDVII/DA chimeric infectious cDNAs to produce intratypic recombinant viruses in order to clarify reasons for the TMEV subgroup-specific difference in demyelinating activity. We found that both the GDVII and DA strains contain a genetic determinant(s) for demyelinating activity. No demyelination occurs following GDVII strain inoculation because this strain produces an early neuronal disease that kills mice before white matter disease and persistent infection can occur. PMID- 2243400 TI - Presidential address: quality assurance and medical economics--their impact on the practice of surgery. PMID- 2243401 TI - Interruption of critical aortoiliac collateral circulation during nonvascular operations: a cause of acute limb-threatening ischemia. AB - In patients with aortoiliac occlusive disease interruption of critical collaterals during another nonvascular or cardiac operation may threaten limb viability. This occurred in four patients whose limb-threatening ischemia was precipitated by radical cystectomy with bilateral hypogastric artery ligation, left colon resection, or coronary artery revascularizations by means of the internal mammary artery. Important collateral pathways, the interruption of which may account for this phenomenon, are detailed, and approaches are outlined for prevention and management of acute ischemia in this setting. PMID- 2243403 TI - One hundred percent oxygen reverses muscle hypoxia in a rat hindlimb model of acute arterial occlusion. AB - Significant morbidity results from extremity ischemia after acute arterial occlusion. Reestablishment of arterial flow is considered to be the ideal treatment, yet substantial tissue loss can occur before this is accomplished. Using a rat hindlimb model we investigated whether the administration of 100% oxygen would decrease tissue hypoxia from acute arterial occlusion. Adult male Sprague-Dawley rats were used, and Po2 recordings were taken from the gastrocnemius muscle by use of an oxygen electrode. Baseline muscle Po2 was recorded, and then the femoral artery was occluded. Repeat recordings were made after 20 minutes of ventilation with room air and after an additional 20 minutes of ventilation with 100% oxygen (N = 10). Control groups consisted of animals undergoing occlusion but continued on room air (N = 3) and animals undergoing sham occlusion but receiving the period of 100% oxygen ventilation (N = 3). Femoral artery occlusion produced a reduction in muscle Po2 from 28.0 +/- 1.4 to 6.1 +/- 2.0 (mean +/- SEM, p less than 0.001). Ventilation with 100% oxygen reversed the tissue hypoxia produced by occlusion (27.3 +/- 2.0, p less than 0.001). The administration of 100% oxygen without femoral artery occlusion resulted in a higher tissue Po2 than the occluded + oxygen group (94 +/- 12 vs 27.3 +/- 2.0, p less than 0.001). Mean arterial blood pressure increased in the experimental group concomitant with the administration of 100% oxygen, but there was no correlation between final blood pressure and final tissue oxygen tension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243402 TI - Atheroemboli to the lower urinary tract: a marker of atherosclerotic vascular disease--a case report. AB - Atheroemboli to the lower genitourinary tract may serve as a marker for disseminated atheroembolic disease, a highly lethal condition. A case presentation and review of our institional experience is presented. PMID- 2243404 TI - Does the end-to-end venous anastomosis offer a functional advantage over the end to-side venous anastomosis in high-output arteriovenous grafts? AB - This study explores the hemodynamics, mechanics, and biologic response of end-to end versus end-to-side venous anastomoses in a canine arteriovenous graft model. Femoral polytetrafluoroethylene grafts were implanted bilaterally in a paired fashion (n = 22). Detailed local hemodynamic measurements were made by use of color Doppler ultrasound imaging at 1, 4, 8, and 12 weeks after implant. Measurements included volumetric flow rate and Doppler-derived spectral window (percent window) as a measure of turbulence. Amplitude and velocity of vessel wall movement were also measured. Volume of perivascular tissue vibration quantitated kinetic energy transfer through the vessel wall. Volumetric flow rate (end to end, 1013 +/- 70 ml/min; end to side, 1015 +/- 72 ml/min), percent window (end to end, 6.6% +/- 0.6%, end to side, 5.6% +/- 0.4%) and volume of perivascular tissue vibration (end to end, 19.6 +/- 1.2 ml, end to side, 16.3 +/- 1.8 ml) were statistically equivalent in the two graft types (end to end vs end to side p greater than 0.05). Both graft types developed venous intimal-medial thickening of a similar magnitude: end to end, 0.35 +/- 0.05 mm, end to side, 0.43 +/- 0.09 mm, normal vein 0.070 +/- 0.004 mm (analysis of variance [ANOVA] p less than 0.001, p less than 0.01 for end to end or end to side vs control, end to end vs end to side p greater than 0.05 by Student-Newman-Keuls test). The best correlations with venous intimal-medial thickening were obtained from inverse percent window (r = 0.84, p less than 0.001) and volume of perivascular tissue vibration (r = 0.68, p less than 0.001). In the end to end configuration the relative amplitude of venous wall movement decreased, and the relative velocity of wall motion increased over time. We conclude that in the circumstances of this high flow arteriovenous graft model the end-to-end venous anastomosis does not significantly differ from the end-to-side venous anastomosis in terms of flow stability, turbulence, or kinetic energy transfer. The magnitude of the hyperplastic response is statistically equivalent for the two anastomotic types, but the pattern is somewhat different, possibly providing evidence for differences in stress distribution. Differences in the relative amplitude and velocity of vessel wall movement suggest that anastomotic geometry may affect the way in which kinetic energy is dissipated at the graft/vessel interface. PMID- 2243405 TI - End-stage renal disease--is infrainguinal limb revascularization justified? AB - Reports of reconstructive surgery for peripheral vascular disease have been relatively uncommon in patients with end-stage renal disease. Between 1980 and 1989, 39 patients with end-stage renal disease underwent revascularization of 56 limbs. Fifty-two primary infrainguinal and four secondary infrainguinal bypass grafts were performed. In addition, nine thrombectomies were performed. At the time of surgery 37 patients were on dialysis; three had functioning kidney transplants. The indications for revascularization were gangrene, rest pain, or ulceration in all except three limbs with disabling claudication. Reversed, nonreversed, or in situ vein was used in 25 of the 52 primary infrainguinal revascularizations performed. Polytetrafluoroethylene was used in 25. Two procedures used a combination of polytetrafluoroethylene and vein. The primary patencies for all infrainguinal procedures at 1 and 2 years were 77% and 68%, respectively. Four perioperative deaths occurred in the infrainguinal group (7.7%). An additional death occurred after thrombectomy for late graft closure. Three deaths were a result of myocardial infarction. One patient on peritoneal dialysis developed uncontrolled sepsis. At 3 years 39% of patients were alive, and 84% of the limbs were salvaged. Among the cases studied no group was identified that represented unacceptable operative risk. Results compared well with reported patencies for patients subjected to infrainguinal revascularization procedures. Limb revascularization in patients with end-stage renal disease may be performed by use of similar criteria to those used for other patients with peripheral vascular disease. PMID- 2243406 TI - Transaortic endarterectomy of renal visceral artery lesions in association with infrarenal aortic surgery. AB - The complexity of infrarenal aortic reconstruction increases when bypass grafts to revascularize associated renal and visceral arteries are needed. Lesions in these vessels, however, are usually limited to their aortic orifices and therefore are amenable to retroperitoneal transaortic endarterectomy. A combined infrarenal aortic reconstruction and transaortic endarterectomy of the renal/visceral vessels was used in 18 (16%) of 120 patients undergoing elective infrarenal aortic reconstruction over a 2-year-period. Transaortic endarterectomy was performed primarily for renal preservation in 11 patients with bilateral, high-grade renal artery stenoses and abnormal renal function (serum creatinine greater than or equal to 1.9 mg/dl). In seven patients transaortic endarterectomy was performed as a secondary procedure during the course of complex reconstruction of aneurysmal or occlusive aortic disease. Mean serum creatinine, which was elevated preoperatively in 14 (78%) patients (3.3 mg/dl), decreased significantly after the operation (2.0 mg/dl, p less than 0.01). A single death occurred in the 18 patients undergoing transaortic endarterectomy. Renal function preservation can be achieved by renal revascularization in patients with bilateral renal artery stenoses and decreased renal function. The retroperitoneal approach to aortic reconstruction and the use of transaortic endarterectomy allows correction of most renal/visceral vessel involvement in complex aortic revascularization procedures. PMID- 2243407 TI - Combined aortic and visceral arterial reconstruction: risks and results. AB - The indications, morbidity, and efficacy of combined reconstruction of the abdominal aorta and visceral arteries (renal and superior mesenteric; excluding suprarenal aortic aneurysms) were analyzed retrospectively in 29 consecutive patients who underwent surgery from June 1984 through February 1990. Seventeen men and 12 women ages 32 to 76 years (mean, 66 years) were studied. Follow-up was complete in all patients to either death or calendar year 1989 to 1990 (mean, 31.9 months; range, 2 to 66 months). All patients underwent bypass of angiographically proven severe lesions of one renal artery (19 patients), both renal arteries (8 patients), or the superior mesenteric artery and renal arteries (2 patients), in concert with synthetic distal aortic replacement for occlusive disease (10 patients) or aneurysm (19 patients). Indications for renal artery repair included severe hypertension in 13 patients, ischemic renal insufficiency in 8 patients, and lesion morphology alone in 8 patients. Operative mortality rate was 3 of 29 (10.3%), and each death was the result of multisystem organ failure. Nonfatal complications occurred in 11 of the 26 survivors (42%), and this group differed significantly from the uncomplicated 15 patients only in having a higher mean preoperative serum creatinine (2.5 +/- 1.1 mg/dl vs 1.6 +/- 0.9 mg/dl, p = 0.04, t test). The mortality rate of patients with preoperative serum creatinine greater than or equal to 2.0 mg/dl, was 15.4% (2/13 patients), compared to 6.2% (1/16) in patients with creatinine less than 2.0 mg/dl. Three late deaths occurred (2 stroke, 1 cancer). Hypertension control improved in 64% of patients overall, and in 7 of 9 patients whose major operative indication was renovascular hypertension. Renal function remained stable or improved in 12 of 15 patients (80%) with renal insufficiency, but 3 patients progressed to require dialysis. Long-term graft patency was demonstrated by angiography or on duplex scan in all studied survivors (21 patients). Although operative risks are clearly increased compared to less complex vascular procedures, careful patient selection and management will yield a favorable outcome in most patients with such combined lesions. PMID- 2243408 TI - The role of carotid screening before coronary artery bypass. AB - Five hundred thirty-nine patients with no symptoms of cerebral ischemia undergoing coronary artery bypass were preoperatively evaluated for presence of carotid stenosis by noninvasive methods (duplex scanning and ocular pneumoplethysmography-Gee). Overall prevalence of carotid stenosis greater than 75% was higher (8.7%) than that generally reported. Age greater than 60 years was significantly related to presence of carotid stenosis greater than 75% (11.3% vs 3.8%, p = 0.003). Risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, and smoking were not predictive for carotid stenosis, postoperative stroke, or death. Carotid stenosis greater than 75% (odds ratio 9.87, p less than 0.005) and coronary artery bypass redo (odds ratio 5.26, p less than 0.05) were both independent predictors of stroke risk. Patients were divided into four groups: group 1, minimal or mild degree of carotid stenosis (less than 50%), not submitted to prophylactic carotid endarterectomy (432 patients, 80.1%); group 2, moderate degree of stenosis (50% to 75%), no prophylactic carotid endarterectomy (60 patients, 11.2%); group 3, severe carotid stenosis; (greater than 75%), submitted to prophylactic carotid endarterectomy (19 patients, 3.5%), group 4, severe carotid stenosis (greater than 75%) no prophylactic carotid endarterectomy (28 patients, 5.2%). Patients in group 4 had significantly higher stroke rate (14.3%) compared to the other three groups (1.1%) (p = 0.0019). The finding of carotid stenosis greater than 75% in patients over 60 years of age was associated with occurrence of stroke in 15% of cases. Carotid screening is helpful to determine patients at increased risk of stroke and should be performed in patients greater than 60 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243409 TI - Carotid endarterectomy: a ten-year analysis of outcome and cost of treatment. AB - Between 1978 and 1988, 215 patients with an average age of 67 years, underwent 246 carotid endarterectomies. Two hundred ten (85.4%) patients were symptomatic, and 36 (14.6%) were asymptomatic. Six patients (2.4%) had a postoperative stroke, and all had immediate reoperation. One of these patients died (30 day mortality rate, 0.4% for the series), and two (0.8%) recovered completely, whereas three (1.2%) had a mild permanent neurologic deficit. Two patients (0.8%) had nonfatal myocardial infarction. Mean follow-up of 42.2 months (range, 1 to 126 months) was achieved. At 5 and 8 years actuarial survival rates of 82% and 66% and stroke free survival rates of 67% and 37% were observed. Actuarial stroke free rates of 90% at 5 and 8 years were noted. By introducing and observing guidelines that required preoperative study of most clearly defined classes of patients before admission for surgical treatment, the average length of stay for carotid endarterectomy was lowered from 9.5 days in the first 5 years of the study to 5.8 days in the second 5 years (p = 0.001). Average hospital charges, expressed in constant dollars, decreased from $3113 in the first 5 years to $2620 in the second 5 years (p = 0.02) despite an 88% inflationary increase in medical consumer price index. This experience shows that the length of hospitalization of patients with carotid endarterectomy can be reduced and the cost of admission lowered without untoward effect on perioperative morbidity and mortality rates. PMID- 2243410 TI - Steady and pulsatile flow fields in an end-to-side arterial anastomosis model. AB - We investigated the flow field within a rigid-walled in vitro model of an end-to side 45 degree anastomosis in an attempt to identify possible hemodynamic factors that may contribute to the pathogenesis of distal anastomotic intimal hyperplasia. A high-resolution photochromic tracer technique was used to visualize the flow in orthogonal planes and to determine the axial wall shear stress profiles for both steady and pulsatile flows over a range of physiologically relevant conditions. The flow field showed qualitative similarities to those seen in curved vessel: rapidly moving fluid from the graft section affects the bed of the host vessel, that is, the wall opposite the anastomosis, eventually advancing down the host vessel in a spiraling motion. A small mobile separation zone was noted at the toe of the anastomosis. Comparison of wall shear stress profiles with previously reported preferential sites for the development of intimal hyperplasia supported a low wall shear stress and/or flow separation pathogenesis hypothesis. One notable exception was the bed of the host artery that appeared to be subjected to a complex hemodynamic environment. PMID- 2243411 TI - The value of pulmonary artery and central venous monitoring in patients undergoing abdominal aortic reconstructive surgery: a comparative study of two selected, randomized groups. AB - One hundred two patients undergoing abdominal aortic reconstructive surgery were prospectively, randomly allocated to two groups, one of which was monitored with a central venous catheter and the other with a pulmonary artery catheter. Patients with uncompensated cardiopulmonary or renal disease were excluded from the study. General anesthesia was administered for the surgical procedure, and the patients were followed through hospital discharge. No statistically significant differences occurred between the two groups with regard to morbidity (perioperative cardiac, pulmonary or renal sequelae), mortality rate, duration of intensive care, postoperative hospital stay, or cost of hospitalization. The one statistically significant difference between groups was the professional fee charged for anesthetic care, which was higher for patients with pulmonary artery catheters than for those with central venous catheters. In conclusion, we prospectively gathered data from most patients presented for abdominal aortic reconstructive surgery. Our data seem to indicate that the choice of central venous catheter or pulmonary artery catheter monitoring makes little difference in outcome after abdominal aortic reconstructive surgery, and that for many patients pulmonary artery catheters are not necessary to give appropriate, adequate care. Because of the size of the sample, however, declarations of epidemiologic significance would be unfounded. Therefore large-scale, multicenter studies addressing such outcomes remain necessary. PMID- 2243412 TI - Composite femoropopliteal bypass: a new method of centered end-to-end anastomosis between polytetrafluoroethylene and autologous vein with a diameter discrepancy. PMID- 2243413 TI - Expanded indications for laser-assisted balloon angioplasty in peripheral arterial disease. PMID- 2243414 TI - Institute of Medicine to restaurants: serve up nutrition information. PMID- 2243415 TI - Cholesterol 'war': dietitians, physicians team up. PMID- 2243416 TI - Medical students to receive food for thought. PMID- 2243417 TI - Youngsters dialing up cholesterol levels? PMID- 2243418 TI - Nursing: new power, old problems. PMID- 2243419 TI - From the Centers for Disease Control. Factors related to cholesterol screening, cholesterol level awareness--United States, 1989. PMID- 2243420 TI - Myopathy and rhabdomyolysis with lovastatin taken with gemfibrozil. PMID- 2243421 TI - Increases in creatine kinase after exercise in patients treated with HMG Co-A reductase inhibitors. PMID- 2243422 TI - Lymphadenopathy associated with severe hypertriglyceridemia. PMID- 2243423 TI - Hypothermia precipitated by ice-cold beverages in a wasted dialysis patient. PMID- 2243424 TI - Oxybutynin for diabetic complications. PMID- 2243426 TI - Prevalence of Alzheimer's disease. PMID- 2243425 TI - Nursing homes and fax machines. PMID- 2243427 TI - A piece of my mind. The poetry of medicine. PMID- 2243428 TI - Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens. AB - We conducted a randomized, controlled trial in 72 patients with heterozygous familial hypercholesterolemia to test whether reducing plasma low-density lipoprotein levels by diet and combined drug regimens can induce regression of coronary lesions. Four hundred fifty-seven lesions were measured before and after a 26-month interval by computer-based quantitative angiography. The primary outcome variable was within-patient mean change in percent area stenosis. Mean low-density lipoprotein cholesterol levels decreased from 7.32 +/- 1.5 to 4.45 +/ 1.6 mmol/L. The mean change in percent area stenosis among controls was +0.80, indicating progression, while the mean change for the treatment group was -1.53, indicating regression (P = .039 by two-tailed t test for the difference between groups). Regression among women, analyzed separately, was also significant. The change in percent area stenosis was correlated with low-density lipoprotein levels on trial. We conclude that reduction of low-density lipoprotein cholesterol levels can induce regression of atherosclerotic lesions of the coronary arteries in patients with familial hypercholesterolemia. The anticipation of benefit from treatment applies to women and men alike. PMID- 2243429 TI - Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up. AB - The Cholesterol Lowering Atherosclerosis Study (CLAS) was a randomized, placebo controlled, angiographic trial testing combined colestipol-niacin therapy in 162 subjects. Two-year results (CLAS-I) showed decreased atherosclerosis progression and increased regression. We now describe a subgroup of 103 subjects treated for 4 years (CLAS-II). Changes in blood lipid, lipoprotein-cholesterol, and apolipoprotein levels were maintained, and at 4 years significantly more drug treated subjects demonstrated nonprogression (52% drug- vs 15% placebo-treated) and regression (18% drug- vs 6% placebo-treated) in native coronary artery lesions. Significantly fewer drug-treated subjects developed new lesions in native coronary arteries (14% drug- vs 40% placebo-treated) and bypass grafts (16% drug- vs 38% placebo-treated). These results confirm CLAS-I findings and indicate that regression can continue for 4 years. They reaffirm the need for early initiation of vigorous long-term lipid lowering therapy in coronary bypass subjects. PMID- 2243430 TI - Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking. A preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. AB - Investigators in eight communities collected aortas, right coronary arteries, blood, and associated information from 390 males, 15 to 34 years of age, who died of violent causes. Pathologists at central laboratories graded the arteries for atherosclerotic lesions, and serum lipoprotein cholesterol and thiocyanate concentrations were measured. The percentage of intimal surface involved with atherosclerotic lesions in both the aorta and the right coronary artery was positively associated with serum very low-density lipoprotein + low-density lipoprotein cholesterol concentration and negatively associated with serum high density lipoprotein cholesterol concentration. The serum thiocyanate concentration, a marker for smoking, was strongly associated with prevalence of raised lesions, particularly in the abdominal aorta. The effect of smoking was not explained by lipoprotein levels. Blacks had more extensive total surface involvement of the aorta after adjustment for lipoprotein cholesterol levels and smoking. These associations indicate that serum lipoprotein cholesterol concentrations and smoking are important determinants of the early stages of atherosclerosis in adolescents and young adults. PMID- 2243431 TI - Use of cholesterol measurements in childhood for the prediction of adult hypercholesterolemia. The Muscatine Study. AB - This article describes the validity and utility of screening tests for total cholesterol levels in school-age children to predict those who, when adults, will have cholesterol levels that the National Cholesterol Education Program suggests need continuing surveillance and intervention. Two thousand three hundred sixty seven children aged 8 to 18 years were examined on several occasions and were followed up to ages 20 to 30 years. Of children with cholesterol concentrations exceeding the 75th percentile on two occasions, 75% of girls and 56% of boys would not qualify for intervention as adults by the National Cholesterol Education Program criteria. Of children with cholesterol levels exceeding the 90th percentile on two occasions, 57% of girls and 30% of boys would not qualify for intervention as adults. Because the efficacy, safety, acceptability, and cost of treatment for high cholesterol concentrations in childhood is evolving, the need for universal screening of childhood cholesterol levels must be considered carefully in view of the number of children with high levels of cholesterol who, as adults, do not meet the criteria for intervention suggested by the National Cholesterol Education Program. PMID- 2243432 TI - The case against childhood cholesterol screening. AB - Because some authorities have proposed blood cholesterol screening for children to prevent coronary heart disease, we reviewed published studies to estimate the potential risks and benefits of such screening. Childhood cholesterol levels are a poor predictor of high cholesterol levels in young adulthood and will be an even poorer predictor of coronary heart disease later in life. There is no evidence that blood cholesterol levels can be lowered more easily in children than in adults, and it seems unlikely that cholesterol reduction in childhood will be much more effective at preventing coronary heart disease than cholesterol reduction begun in middle age. Screening and interventions to lower blood cholesterol levels for millions of children would be expensive, could lead to labeling and family conflicts, and may cause malnutrition and increased noncardiovascular mortality. Because the benefits of cholesterol screening are unlikely to exceed these risks, we conclude that children should not be screened for high blood cholesterol levels. PMID- 2243433 TI - A single cholesterol measurement underestimates the risk of coronary heart disease. An empirical example from the Lipid Research Clinics Mortality Follow-up Study. AB - In prospective epidemiologic studies of coronary heart disease, a single measurement of cholesterol is made to assess its relationship to the risk of coronary disease. Statistical theory states that if this measurement is subject to within-individual variability, the strength of the relationship will be underestimated. This is empirically shown for the example of plasma cholesterol. For the Lipid Research Clinics Follow-up Study population (comprising 2170 white men over 30 years of age), the age-adjusted coronary heart disease mortality regression coefficient increases from .453 to .496 if the average of two cholesterol measurements is used instead of a single measurement. Since the correlation between the two repeated cholesterol measurements is .815, an increase in the regression coefficient up to .556 would be expected if the true cholesterol values were available. Thus, epidemiologic studies have substantially underestimated the strength of the relationship between cholesterol levels and the risk of coronary disease by calculating the relationship on the basis of a single cholesterol determination. PMID- 2243434 TI - Lipoproteins and atherogenesis. Current concepts. AB - The frontiers in atherosclerosis research are moving from lipoprotein metabolism and control of hyperlipidemia to the cellular events in the artery wall. Emerging hypotheses, including the oxidative modification hypothesis, are already suggesting new approaches that could complement and be additive to control of hypercholesterolemia in the prevention of atherosclerosis. PMID- 2243436 TI - Cholesterol redux. PMID- 2243435 TI - Cholesterol and coronary heart disease. Future directions. AB - The importance of high serum cholesterol levels as a risk factor for coronary heart disease and the benefit of lowering cholesterol levels for reducing risk are being increasingly accepted. A broad consensus to this effect has led to the establishment of the National Cholesterol Education Program. Although the available evidence fully justifies this program, its practical application to the American public has generated a series of new questions that must be explored. For example, it can be questioned whether reduction in coronary risk through lowering cholesterol levels extends to both sexes and all age groups. For people with high cholesterol levels, dietary modification is undoubtedly the first step of management, but the fraction of people responding adequately to dietary change remains to be determined. Finally, indications for drug therapy and choice of drugs need further exploration, particularly in the area of cost vs benefit. Thus, continuing research must be carried out in parallel with clinical and public health application of cholesterol education. PMID- 2243437 TI - Treatment of a low HDL cholesterol level. PMID- 2243438 TI - Cholesterol values and the fasting state. PMID- 2243439 TI - Innocent enzyme elevations. PMID- 2243440 TI - Phil Sokolof fights the 'fatting' of America. PMID- 2243441 TI - DNA ploidy level and S-phase fraction as prognostic factors in breast cancer. AB - Imprint smears from sixty cases of breast cancer made after mastectomy were stained by the Feulgen method and the nuclear DNA content measured by a cytofluorometer equipped with an incident illumination system. After logarithmic transformation of the fluorescence intensity, the ploidy level and S-phase fraction (SPF) were calculated with a microcomputer and the correlation between the ploidy level or SPF and the clinicopathological prognostic factors studied. Patients with tumors of a larger diameter and more extensive lymph node involvement had higher levels of ploidy and SPF and the ploidy level in the metastatic lymph nodes was higher than that in the primary lesion. Moreover, a significant increase in SPF was observed in the metastatic lymph nodes and a high ploidy level found to be associated with tumors having a negative estrogen receptor. When the tumors were divided into a diploid group and an aneuploid group, the diploid group showed a significantly better prognosis than the aneuploid group, in 6-year survival. Similarly, the groups in which SPF was less than 20.0 per cent had significantly better prognoses than the group in which SPF was 20.1 per cent or more. These prognostic factors were evaluated with Cox's proportional hazard model and a significant correlation observed in lymph node status, ER status, ploidy level and S-phase fraction. It was thus concluded that ploidy level and SPF are important and independent prognostic factors for predicting the postoperative course of breast cancer patients. PMID- 2243442 TI - The clinical features and prognosis of rhabdomyosarcoma: follow-up studies on pediatric tumors from the Japanese Pediatric Tumor Registry 1971-1980. Part II. Committee of Malignant Tumors, Japanese Society of Pediatric Surgeons. AB - A retrospective study was conducted on 126 patients with rhabdomyosarcoma enrolled in the Japanese Pediatric Tumor Registry between 1971 and 1980. The age of the patients ranged from less than 1 year to 15 years, and the male to female ratio was 1.3:1.0. Primary sites included the pelvis (37.3 per cent), abdomen (23.8 per cent), head and neck (21.4 per cent), thorax (9.5 per cent), extremities (6.4 per cent) and unknown (1.6 per cent). According to the staging system of the Japanese Society of Pediatric Surgeons, the extent of disease was classified into stages Ia (26.2 per cent of the total); Ib (14.6 per cent); II (12.6 per cent), III (29.1 per cent) and IV (17.5 per cent). The clinical stage was significantly correlated with survival outcome in this series (p less than 0.05). Age, sex, histology and primary site per se had no independent prognostic influence on tumor-free survival. With regard to treatment modalities, surgery was performed in 94.0 per cent of the patients, and radiotherapy at a mean dose of 37 Gy, and/or multi-agent chemotherapy in 41.7 per cent and 80.0 per cent, respectively. The patients who underwent total excision had a better survival outcome than those who did not (p less than 0.05). Combination chemotherapy such as VAC was more commonly administered in the latter study period. The overall 2 year tumor-free survival rate (2YTFSR) significantly improved from 24.0 per cent in the former period between 1971 and 1975 to 48.7 per cent in the latter period between 1976 and 1980 (p less than 0.05). PMID- 2243443 TI - Flow cytometric DNA analysis of thyroid carcinoma. AB - Abnormal DNA content has been considered as an additional criterion for determining the biological behavior of a tumor. Flowcytometric DNA analysis was done on 121 patients with thyroid carcinoma encountered during the period between 1975 and 1987. Tumor tissues were sampled from paraffin-embedded blocks and the histology of thyroid carcinoma found to consist of 91 papillary, 23 follicular, 2 medullary, 1 squamous cell and 4 anaplastic carcinomas. The incidence of aneuploidy in thyroid carcinoma was 7.4 per cent (9 patients) while that of diploidy was 92.6 per cent (112 patients). The aneuploid specimens consisted of 6 papillary, 1 follicular, 1 medullary and 1 anaplastic carcinomas and, of 4 anaplastic carcinoma patients with subsequent death within 6 months, only 1 was aneuploid. As an indicator of proliferative potential, S-phase fraction (SPF) was also determined by flow cytometry, but this could not be used as an independent prognostic factor. The aneuploid patients showed a significantly decreased survival rate (p less than 0.01). Thus, although DNA measurement proved useful for predicting the survival of aneuploid patients, there is some discrepancy between DNA content and the biological behavior of the tumor. PMID- 2243444 TI - Duodenal tuberculosis: a review of the clinicopathologic features and management of twelve cases. AB - A retrospective analysis of twelve cases of duodenal tuberculosis is presented herein. The average age of the patients was 31.4 years with a male to female ratio of 2:1. The presenting complaints were duodenal obstruction in six patients and subacute intestinal obstruction in three. None of the patients had associated pulmonary tuberculosis. Eight patients had isolated duodenal tuberculosis, two of whom were successfully treated with antitubercular drugs. In four patients, the diagnosis was established at laparotomy by the presence of tubercles over the duodenum. Five patients required a bypass procedure for obstruction caused by the duodenal tuberculosis and one patient was operated on for uncontrollable bleeding from a tubercular duodenal ulcer. All patients remained symptom free after treatment, whether medical or surgical. Thus, in areas where tuberculosis is endemic, even in the absence of pulmonary tuberculosis, duodenal tuberculosis should be suspected in patients with upper gastrointestinal obstruction or in patients with peptic ulcer like symptoms not responding to medical therapy. PMID- 2243445 TI - A clinicopathological study on intrahepatic cholesterol gallstones. AB - In order to clarify the pathogenesis and process of the formation of intrahepatic cholesterol gallstones, we examined the clinical features, cholangiograms and pathological findings of eight patients with intrahepatic cholesterol gallstones. When examining the clinical features, one patient was found to have developed intrahepatic cholesterol gallstones 3 years after a complete lithotomy. The cholangiograms of two patients revealed small gallstones in the peripheral bile ducts of the lateral segment of the liver, and these bile ducts showed localized cystic dilatation and were tightly filled with gallstones. Conversely, their other bile ducts which contained no gallstones showed an entirely normal cholangiogram. Pathologically, these two cases showed mild chronic cholangitis, and cholesterol crystals in the peripheral bile ducts. The other six cases showed moderate or severe dilatation of the bile duct and severe chronic proliferative cholangitis. From the above results, we proposed the following theory to explain the pathogenesis and process of the formation of intrahepatic cholesterol stones: The cholesterol crystals in the peripheral intrahepatic bile ducts may be a primitive form of intrahepatic cholesterol gallstones, and the formation of intrahepatic cholesterol gallstones may precede and cause such deformities of the bile ducts as strictures or dilatations. PMID- 2243446 TI - Bone mineral analysis and X-ray examination of the bone in patients with biliary atresia. AB - Investigations of bone mineral content, X-ray of the radius and ulna and serum biochemical analysis were performed in 10 children with biliary atresia (B.A.) and 150 healthy children. The patients were classified into 2 groups, namely; group A, comprised of 5 patients whose postoperative courses went well, and group B, comprised of 5 patients who developed various degrees of liver disturbance postoperatively. The ratio of bone mineral content (BMC) to bone width (BW) (BMC/BW) increased in accordance with age in the healthy children and the patients of group A, but was relatively slow in the patients of group B. Signs of rickets were found on the X-rays of 4 of the 10 patients, while serum levels of calcium and 25-OH-vitamin D in the group B patients were significantly lower than those in the group A patients or healthy children. Serum levels of alkaline phosphatase (Alp) fluctuated, but serum Alp was elevated in all the patients with rickets. PMID- 2243447 TI - The clinical significance of venous invasion in cancer of the stomach. AB - Specimens from 235 surgically treated cases of gastric cancer were examined for venous invasion in order to investigate its clinical significance. A total of 87 (37.0 per cent) cases showed histologic evidence of venous invasion, with the incidence being 48.3 per cent of 180 cases, after the exclusion of 55 cases where cancerous invasion was limited to the mucosa. The frequency of venous invasion varied with the gross type of tumor, the depth of penetration and the degree of differentiation, being highest in tumors of type 2 and moderately differentiated adenocarcinoma. It increased proportionately depending upon the depth of penetration and the incidence increased in cases where there was evident lymphatic invasion or lymph node metastasis. The long term survival rate significantly decreased in patients with venous invasion when compared to those without it. In this report, we also discuss the marked difference in the incidence of liver metastasis between gastric and colorectal carcinomas in relation to venous invasion of the primary tumor. Double staining with Victoria blue and hematoxylin-eosin for elastic fibers proved useful for detecting venous invasion in the carcinomatous tissue, though endothelial markers have great specificity for differentiating small veins from lymphatics. PMID- 2243448 TI - Does H2-receptor antagonist alter the renal function of cyclosporine-treated kidney grafts? AB - Histamine-type 2 antagonists (H2-blockers) as represented by cimetidine have been shown to adversely affect renal allograft function, particularly when coadministered with cyclosporine, currently a major immunosuppressant. To determine whether or not a newer and more powerful H2-blocker, famotidine, would produce similar adverse effects, we assessed seven cyclosporine-treated renal allograft recipients with regard to changes in their renal function on or off the H2-blocker over a one-week period. Neither the administration nor withdrawal of famotidine (20-40 mg/day) resulted in any significant changes in serum creatine, BUN, urine output or cyclosporine trough levels, suggesting that famotidine can be safely administered as an H2-blocker to cyclosporine-treated renal allograft recipients. PMID- 2243449 TI - Thymic carcinoid--a case report and review of the literature. AB - We report herein a case of a patient with thymic carcinoid who was operated on twice and has been followed for 9 years. In 1979, the original tumor was removed through an emergency left thoracotomy incision done for a hemothorax caused by an anterior mediastinal biopsy. Tumor recurrence was found 6 years later and removal carried out through a median sternotomy. The patient has been working and enjoying life following radiation and chemotherapy for a total of 9 years after his first operation. Recurrent thymic carcinoid has been thought to carry a poor prognosis, but this successfully treated case has been followed up for a long time after the removal of his recurrent tumor. We present this case and discuss other such cases reported in the Japanese literature. PMID- 2243450 TI - Hiatal herniation of the colon with digestive tract bleeding--a case report. AB - A 71 year old woman with hiatal herniation was admitted to our hospital with anemia and melena. A barium enema revealed hiatal herniation of the transverse colon in conjunction with the stomach, which seemed to be strangulated by the esophageal hiatus. She underwent surgery, for which Hill's gastropexy method was employed and has had no signs of bleeding since. By presenting this case, we stress the importance of marking a careful differential diagnosis due to the variability in symptoms of digestive tract bleeding. PMID- 2243451 TI - Pilonidal disease of the umbilicus--a report of two cases. AB - Two cases of umbilical pilonidal sinus are reported herein. Both patients were young adult males aged 21 and 27 years, respectively. The predisposing factors are briefly discussed, however, the exact etiology of this disease remains unknown. Umbilectomy is the most commonly offered treatment and although it is rare, this entity probably goes undiagnosed in the majority of cases. PMID- 2243452 TI - Cervical thymic cyst as a cause of acute suppurative thyroiditis. AB - A case of acute suppurative thyroiditis following a perithyroidal abscess, which was thought to have resulted from infection of a cervical thymic cyst, is reported herein. The patient was an 8 year old asthmatic Japanese boy who originally presented with tender swelling of the left anterior neck in July, 1986. Although pharyngography could not clearly demonstrate the pyriform sinus fistula, a hypoechoic area around the left lobe of the thyroid gland was noted on ultrasonography. Incisional drainage revealed Streptococcus milleri. A diagnosis of acute suppurative thyroiditis was established, and a cystic tubular mass was surgically resected from the left perithyroidal space some time later. Histopathological examination of the specimen revealed partly cystic thymic tissue along with parathyroid tissue. These observations suggested that acute suppurative thyroiditis in this case was caused by a perithyroidal abscess and that a perithyroidal abscess may also result from infection of a cervical thymic cyst. PMID- 2243453 TI - A case of middle lobe syndrome occurring in two sisters. AB - We report herein a rare case of middle lobe syndrome, occurring in two sisters. Since selective aspirations of sputum under bronchoscopic guidance proved ineffective, a middle lobectomy was performed in both cases. Histological findings of the resected specimens showed overgrowth of the bronchial glands, lymphocytic infiltration around the alveoli and glandular metaplasia of the alveoli in both cases. Based on the allergic diathesis, we suggest that in these 2 sisters, middle lobe syndrome was caused by chronic inflammation. PMID- 2243454 TI - Experimental transcatheter hepatic subsegmentectomy using absolute ethanol in dogs. AB - In this study, we evaluate the effect of an intraportal injection of absolute ethanol in the canine liver and discuss how to introduce it in clinical application. The intraportal injection of ten milliliters of ethanol using a balloon occlusion catheter created an evident and well-demarcated necrotic lesion in the right central lobe. Histological examination showed a typical coagulation necrosis with fibrous bands, which became thicker day by day. The weight of the necroses ranged from 5 to 55 grams with an average of 26.0 +/- 5.5 grams (mean +/ SE), which was approximately 20 to 40 per cent of the right central lobe. Complications resulting from the ethanol injection were minimal and although more studies need to be done to clearly establish its safety for cirrhotic patients with hepatoma, this technique may be an easier and less invasive substitute for operative hepatic subsegmentectomy. PMID- 2243455 TI - [Terminal pulmonary infections in autopsy cases that died of lung cancer]. AB - To elucidate the predisposing factors of terminal pulmonary infection in patients with lung cancer, we reviewed the case record of 251 autopsy cases that died of lung cancer in Kyushu University Hospital from 1976 to 1987. The incidence of mycobacteriosis was significantly more frequent in cases treated with antineoplastic therapy and corticosteroid (Group III) than in those with antineoplastic therapy but without corticosteroid (Group II), while the incidence of common bacterial and nonbacterial infections was not significantly different between the two groups. In patients with lung cancer treated with antineoplastic therapy, corticosteroid administration of relatively short duration (less than a month) induced fatal mycobacteriosis. In cases with lymphocytopenia, the incidence of fatal mycobacteriosis was significantly more frequent in Group III than in Group II, whereas the incidence of fatal nonbacterial infection was not. In cases with monocytopenia, both fatal mycobacteriosis and nonbacterial infection were significantly more frequent in Group III than in Group II. In Group III, the incidence of mycobacterial and nonbacterial infections was not different significantly between cases with and without lymphocytopenia or monocytopenia. Thus, in patients with lung cancer, administration of corticosteroid has greater influence on the development and exacerbation of mycobacteriosis than lymphocytopenia or monocytopenia. On the other hand, the influence of corticosteroid on the development and exacerbation of nonbacterial infection was significantly different from that of lymphocytopenia. The administration of corticosteroid and antineoplastic therapy do not increase the incidence of terminal common bacterial infection in patients with lung cancer. PMID- 2243456 TI - [Effect of erythromycin on the generation of neutrophil chemiluminescence in vitro]. AB - In order to elucidate the therapeutic mechanisms of low dose-long term erythromycin (EM) therapy in patients with diffuse panbronchiolitis (DPB), the authors evaluated the effect of in vitro EM treatment on neutrophil (PMN) oxygen radicals production. EM has potent capacity to suppress PMN chemiluminescence (CL) induced by the N-formyl Met-leu-phe (FMLP), opsonized zymosan, and calcium ionophore A23187 stimulation. In marked contrast, phorbol myristate acetate (PMA) induced PMN CL were much less affected by EM treatment. The suppressive activity of EM was dependent on the EM concentration and at a EM concentration of 25 micrograms/ml, FMLP-induced PMN CL were suppressed by 45.3 +/- 5.6% (n = 7), but PMA-induced CL were suppressed only marginally, 11.9 +/- 3.7% (n = 7). The onset of inhibitory activity of EM is rapid and at 5 min., 60.1% of the maximum suppression at 60 min. was observed. This EM-induced suppression was found to be reversible and dependent on the EM-pretreatment temperature since the suppressive activity of EM were observed only at 37 degrees C but not at 0 degrees C. These results suggest that actively transported intracellular EM exerts its suppressive activity by inhibiting the process of Ca++ transfer or Ca++ utilization by cells. In addition, these results were consistent with the concept that EM might act as an anti-inflammatory agent in chronic bacterial airway infections such as bronchiectasis and DPB where the PMN appear to play an important role in the generation of airway destruction. PMID- 2243457 TI - [Analysis of immunoglobulin G subclasses in chronic respiratory tract infections]. AB - To analyze the immunological aspects of chronic respiratory tract infections, immunoglobulin G (IgG) subclass patterns were investigated in 20 patients with diffuse panbronchiolitis (DPB) and 20 patients with cystic bronchiectasis (CBE). All IgG subclasses were increased in both diseases in comparison to the normal group. Increased levels of IgG1 and IgG2 were recognized more dominantly in DPB, whereas IgG4 level was elevated in CBE. Furthermore, analysis of the ratio of IgG subclass to total IgG showed increase of IgG1 and decrease of IgG2 in both diseases, and increase of IgG4 only in CBE. On the other hand, the increase of IgG1 correlated with infection by P. aeruginosa while increase of IgG4 was recognized in the group of non-P. aeruginosa infections. These results indicate that increased IgG1 and IgG2 levels are common characteristic phenomena in chronic respiratory tract infections such as DPB and CBE, reflecting the pathophysiological aspects based on respiratory tract defense mechanisms against microorganisms, and demonstrated that differences of IgG subclass patterns are observed among DPB and CBE, and also according to causative agents. PMID- 2243458 TI - [Respiratory malignancies induced by asbestos exposure and evaluation of cases with typical pleural malignant mesothelioma and lung cancer with asbestosis]. AB - Asbestos exposure induces lung fibrosis, i.e. asbestosis, and furthermore, pathological changes of pleura, i.e. asbestos pleurisy of pleural plaque. Generally, asbestosis is induced by massive exposure to asbestos and pleural changes are induced by low dose exposure to asbestos. The most important diseases which are induced by asbestos exposure are malignancies, especially malignant mesothelioma and lung cancer. Two cases, one malignant mesothelioma, the other lung cancer with asbestosis induced by asbestos exposure received almost the same dose of asbestos, as estimated from the period of asbestos exposure and occupational history and the same kind of asbestos (crocidolite) and had a smoking history. We do not know which elements may induce malignancies under asbestos exposure. Recently, some reports described that asbestos mediated the transformation of genes and this action induced malignancies. We should extend our study to the gene problem in cases of malignant mesothelioma and lung cancer induced by asbestos exposure. PMID- 2243459 TI - [Plasma DNA level as a tumor marker in primary lung cancer]. AB - The plasma level of human DNA was determined by the dot-hybridization method using human Alu-family DNA as a probe in 45 patients with primary lung cancer, 54 patients with benign pulmonary diseases, and 59 healthy controls. The mean plasma DNA level was significantly higher in the patients with lung cancer than that in the patients with benign pulmonary diseases or in healthy controls. The mean plasma DNA level in the patients with benign pulmonary diseases was also significantly higher than that in healthy controls. There was no significant difference in mean plasma DNA level in each histologic type of lung cancer. The plasma DNA level was elevated above the cut-off level of 80 ng/ml in 71% of the patients with lung cancer, 37% of the patients with benign pulmonary diseases and none of the healthy controls. The serum CEA was positive in 38% of the patients with lung cancer and thus when plasma DNA and serum CEA were used in combination, 78% of the cases with lung cancer could be detected by these two markers. In the patients with lung cancer who responded to treatment, the plasma DNA levels were significantly decreased after treatment, while its levels were elevated in the patients whose treatment was unsuccessful. These findings indicate that plasma DNA may be a useful marker in patients with lung cancer. PMID- 2243460 TI - [A case of spontaneous regression of malignant lymphoma, complicated with miliary tuberculosis, liver dysfunction and pancytopenia]. AB - An 82-year-old woman was admitted to Iwamizawa Rosai Hospital, Cardiovascular Medicine, for detailed examination of an aneurysm of abdominal aorta. CT scan revealed marked swelling of para-aortic lymph nodes which regressed spontaneously in three months. She was re-admitted to our hospital because of general malaise and gait disturbance. Her chest X-ray on the second admission revealed miliary disseminated shadows, which were confirmed to be tuberculous granuloma by lung biopsy. She was initially well controlled with anti-tuberculosis drugs, followed by severe liver dysfunction and pancytopenia, and died of respiratory and cardiac failure. At autopsy, wide-spread malignant lymphoma and miliary tuberculosis of the lung were found. The cause of liver dysfunction was strongly suspected to be due to infiltration of the lymphoma cells to portal triads of the liver. Hemophagocytosis found in the bone marrow, spleen and liver might be consistent with clinically so-called "hemophagocytic syndrome", causing pancytopenia, associated with infection. PMID- 2243461 TI - [Three patients with typical sandblaster's silicosis proven by mineralogical analysis]. AB - Three family members who had worked as sandblasters in their own sandblasting factory showed innumerable small nodularities in both lung fields of their chest radiograms. One of those showed conglomerate shadows in the upper lung fields. Those shadows seemed to be consistent with those of silicosis. One of the patients was examined by transbronchial lung biopsy (TBLB) and showed typical silicotic nodules. Mineralogical studies were done on the abrasive particles and the deposited particles in the lung tissue specimen obtained via TBLB and bronchoalveolar lavage fluid sample (BALF) using polarized microscopy, X-ray diffraction and analytical electron microscopy. The particles which had accumulated on the floor of the factory mineralogically consisted of mostly (over 90%) silica quartz containing small amount of chlorite, and the deposited particles in the lung tissue and those in the BALF showed similar composition. PMID- 2243462 TI - [A case of sarcoidosis demonstrating spontaneous production of interleukin-1 alpha and beta by alveolar macrophage]. AB - A 44-year-old man was admitted for evaluation of dyspnea on exertion and subcutaneous nodules. The chest X-ray on admission revealed bilateral hilar lymph node swelling and diffuse micronodular shadows throughout both lung fields. Ga scintigram demonstrated diffuse abnormal uptake. Serum angiotensin converting enzyme was elevated significantly (86.6 IU/I). The TBLB specimen confirmed the diagnosis of sarcoidosis. The cell numbers in bronchoalveolar lavage fluid was increased (4.4 x 10(8), the percentage of lymphocytes was elevated (64%) and the ratio of Leu 3a+/Leu 2a+ was very high (16.07). We further evaluated the spontaneous IL-1 release in vitro by alveolar macrophages obtained by bronchoalveolar lavage. The results showed that large amounts of IL-1 alpha and beta were produced spontaneously by alveolar macrophages before therapy, followed by a decrease in production after corticosteroid treatment. Previously, the authors reported that no significant amount of IL-1 alpha and beta was detected in 5 normal volunteers and 6 other active sarcoidosis cases which improved without therapy. Therefore, significant amounts of spontaneous release of IL-1 alpha and beta in vitro from alveolar macrophages in sarcoidosis might be considered as an index for the necessity of systemic corticosteroid treatment. PMID- 2243464 TI - [A case of summer-type hypersensitivity pneumonitis with bronchoalveolar lavage performed 4 years before onset]. AB - A 51-year-old man with chief complaints of cough, fever, and dyspnea was admitted to our hospital. Based on a home provocation test, transbronchial lung biopsy specimens, and a serum antibody, we diagnosed summer-type hypersensitivity pneumonitis. In 1983 when the patient was 46 years old, thymectomy was performed for thymoma. Prior to surgery, bronchoalveolar lavage (BAL) was performed. Total cell count and neutrophils had already increased in BALF. Furthermore, the increase in BALF cell neutrophil count was also seen at the time of admission and after the home provocation test. Because an increase of neutrophils in BALF cells was seen not only at onset but before onset, further studies are required to clarify the role of neutrophils and the factors that increase them in hypersensitivity pneumonitis. PMID- 2243463 TI - [A case of tracheal calculus in the pathogenesis of which fungal infection was probably involved]. AB - A 63-year-old woman with a past history of bronchial asthma was admitted to our hospital with a diagnosis of status asthmaticus. Examination revealed a ring shaped, calcified stone within the trachea immediately below the vocal cords. As the patient complained of increasing difficulty in breathing, emergency tracheotomy was performed in an attempt to save her life, with success. Bronchial calculus (broncholithiasis) has been occasionally reported, and it is hypothesized that the calculus is mostly caused by intra-bronchial perforation of calcified lymph nodes around the bronchus. Tracheal calculus is a rare disease, and our case is only the third ever reported in Japan. However, perforation of calcified lymph nodes was probably not responsible for this case, which probably resulted from repeated chronic inflammation and fungal infection. PMID- 2243466 TI - [Phacoemulsification. Why?]. AB - Improved by both technology and new surgical procedures, phacoemulsification of the nucleus has become increasingly important in extracapsular cataract surgery. Phacoemulsification within the capsular bag has proved to be a valuable surgical technique, yielding predominantly good results. In the hands of a carefully trained, critical surgeon, this procedure results in safe in-the-bag fixation of an intraocular lens. In intravitreal surgery it is almost indispensable. In special cases, such as congenital coloboma, hydrophthalmia in adults, pseudoexfoliation syndrome, risk of expulsive hemorrhage, or in cataract surgery following penetrating keratoplasty, phacoemulsification of the nucleus may be surgically safer than expression of the nucleus through a large corneoscleral incision. PMID- 2243465 TI - [A case of long-term survival of a patient with complicated diffuse metastatic leptomeningeal carcinomatosis secondary to lung adenocarcinoma]. AB - A case of long-term survival of a female patient with complicated diffuse metastatic leptomeningeal carcinomatosis (DMLC) secondary to lung cancer is reported. A 36-year-old woman, hospitalized with a chief complaint of headache and unproductive cough, was diagnosed as having primary lung adenocarcinoma (T4N1M1 oss) and was given systemic chemotherapy. Although progressive deterioration of her headache continued, repeated neurological examination, cerebrospinal fluid (CSF) examination, and cranial CT scans failed to show evidence of metastasis to the central nervous system, and the only finding suggesting CNS involvement was an elevated CEA level in CSF. Later in the course of her treatment, the patient suddenly lost her vision and subsequently consciousness due to acute increased intracranial pressure, and emergency ventricular drainage was performed for therapeutic and diagnostic purposes. Malignant cells were found in CSF obtained from a ventricular drainage and she was treated successfully by systemic and intrathecal chemotherapeutic agents. She was discharged after a ventriculoperitoneal shunt operation for hydrocephalus; a double-dome reservoir was used for continuous intrathecal administration of the anticancer drugs, and a shunt filter was located in the tube to prevent the dissemination of cancer cells. In addition to methotrexate and cytosine arabinoside, ACNU and interleukin-2 were administered intrathecally without serious adverse effects, but no apparent therapeutic effects were noted either. She survived over 2 years after DMLC was first diagnosed. At autopsy DMLC secondary to lung adenocarcinoma was confirmed, but no evidence of leukoencephalopathy due to aggressive intrathecal chemotherapy was found. Current therapy for patients with DMLC and its clinical problems are discussed in relation to our experience in this case. PMID- 2243467 TI - [Initial experience with autologous conjunctiva/limbus transplantation in pterygium]. AB - The present paper reports on the technique and results of conjunctiva/limbus transplantation in 13 eyes with primary or cicatricial pterygium (12 cases and 1 case, respectively). In all cases the pterygia were located nasally. The operation was performed by bare sclera excision, covered with a free graft from the superotemporal conjunctiva and limbus. After a mean follow-up time of 5 months there was only one recurrence. On the basis of a new understanding of limbal diseases the authors believe that conjunctiva/limbus transplantation is an encouraging and appropriate technique for ideal anatomic reconstruction and low recurrence rates in pterygia. PMID- 2243468 TI - [Pre-basal vitreous body after subtotal vitrectomy of aphakic eyes]. AB - The anterior axial vitreous body of aphakic eyes is often severely liquefied. In a vitrectomy case, it was removed easily and completely. The behavior of the prebasal vitreous cortex after the procedure was not predictable. The postoperative biomicroscopic examination resulted in two different findings, are reported on here. PMID- 2243469 TI - [Does silicone oil improve the prognosis of severe proliferative diabetic retinopathy?]. AB - We report on a series of 135 consecutive cases of pars plana vitrectomy for proliferative diabetic retinopathy (average period of observation was 13 months). BSS was used in 69 eyes and silicone oil was used in 66 eyes as a vitreous substitute, the indications for silicone oil in these cases were the presence of several retinotomies or retinectomies as well as sharply increased risk for rebleeding. Postoperatively and after a minimum follow up of 6 months (55 eyes) the two groups with BSS or silicone oil achieved comparable functional results despite the different anatomical preoperative situation. Thus 18 out of 23 eyes of the silicone oil group, originally with detached macula and visual acuity of HM or FC, achieved a visual outcome of greater than = 0.02, showing the best postoperative result. In the BSS-group, with attached macula prior to the operation and same visual acuity, this result is attained by 27 out of 35 eyes. We interpret these figures as meaning, that silicone oil in proliferative diabetic retinopathy reduces some of the problems connected with more advanced retinal changes like retinal detachment and rebleeding thereby allowing a visual outcome which corresponds to the macular condition. PMID- 2243470 TI - [Congenital fibrosis syndrome. Considerations on etiology, genetics and surgical therapy]. AB - Fibrosis syndrome has been a well-known clinical entity for more than a century. Nevertheless, there are still some unresolved questions concerning its etiology, chronological course, and optimal timing of surgery. On the basis of their experience in 12 cases (2 unilateral, 10 bilateral, 7 with eye muscles and/or lid surgery), the authors attempt to help answer these questions. PMID- 2243471 TI - [Normogenesis of the cornea and its modification by cyclophosphamide in the animal experiment]. AB - Animal experiments serving as models have hitherto been indispensable in order to explain pathogenetic processes in the development of malformations. The results presented here are contribution to studies on the normogenesis of the cornea in defined animal material (albino mice of Agnes Bluhm Jena-Halle stock). A single application of cyclophosphamide during embryogenesis caused inhibition malformations. Of these, different degrees of corneal hypoplasia and Peters' malformation are discussed in detail. PMID- 2243472 TI - [Sub-choroidal implanted Greene melanoma: an animal experiment model for malignant choroid melanoma]. AB - A modified technique for subchoroidal transplantation of amelanotic Greene melanoma cells and the intraocular growth patterns of this tumor in rabbit eyes are described. Tumor fragments were implanted via a scleral tunnel in 71 rabbit eyes, with 64 successful tumor growths, producing a prominent, circumscribed choroidal mass within 12-14 days of surgery. Choroidal Greene melanoma in rabbits resembles human epithelioid uveal melanoma in both its growth patterns and morphologic characteristics. The authors' implantation technique guarantees reliable growth of choroidal tumors with easily reproducible size and location. The experimental choroidal melanoma model is particularly valuable in clinical studies where a large number of tumors, with limited variation, is necessary for different experimental groups. PMID- 2243473 TI - [Suitability of different procedures for the sterilization of microsurgical instruments. A review of current and future procedures]. AB - A review of common methods of sterilization is presented. The principles of operation of steam, hot-air, and gas sterilizers, as well as that of a completely new method which uses H2O2 plasma, are described. The suitability of these methods for sterilizing microsurgical instruments was studied. This paper deals in particular with hot-air sterilization, which is preferred because of the low humidity involved. This method was investigated by recording temperature curves during sterilization. Sterilization with hot steam (autoclaving) has been shown to damage instruments by causing corrosion, to which the types of steel used to make these instruments are highly susceptible. A H2O2 plasma sterilization method is described which operates at low temperatures and with very low humidity. Its suitability for microsurgical instruments has been investigated. PMID- 2243474 TI - [Emmetropization. A statistical study]. AB - The relations between bulb length and the refractive power of the cornea were investigated in 3358 eyes of nonselected patients. There was a negative correlation between corneal refraction and bulb length in the range 19 to 29 mm. However, the data do not support the recently advanced hypothesis that corneal curvature and bulb length are regulated by means of optimal retinal contrast. The mean bulb length in males was 23.83 mm, in females 23.25 mm. PMID- 2243475 TI - [Clinical aspects and histopathology of the Cogan-Reese syndrome]. AB - The present paper reports on a 55 year-old patient who had been suffering from progressive essential iris atrophy in her left eye since the age of 24. Ten years later she developed partial secondary angel-closure glaucoma that failed to respond to repeated surgical treatment. Twenty years after onset of the disease, pigmented nodules appeared on the left iris, leading to the diagnosis of Cogan Reese syndrome. Finally, 30 years after onset of the disease, the blind and painful eye was enucleated. The typical histologic findings in Cogan-Reese syndrome were confirmed by light and electron microscopy. PMID- 2243476 TI - [Paraneoplastic retinopathy simulating cone dystrophy with achromatopsia]. AB - A 72-year-old woman developed recurrent blindness on exposure to bright light (sunlight). Examination revealed total achromatopsia; bilateral central scotomas, predominant suppression of the cone response by electroretinography, and narrowing of the retinal arteries on ophthalmoscopy. The general examination revealed a pelvic tumor that later proved to be a pleomorphic carcinoma of presumed uterine origin. The patient died of metastatic disease 9 months after the ocular symptoms developed. Histopathologic examination of the eyes revealed loss of the photoreceptors, most extensive in the macular regions, and selective loss of the cones from the rest of the retinas. No ocular metastases of inflammation were found. The changes described are interpreted as paraneoplastic retinopathy of autoimmune origin. PMID- 2243477 TI - [Birdshot chorioretinopathy: systemic therapy with corticosteroids and nonsteroidal anti-inflammatory drugs]. AB - The symptoms and clinical course of a case of birdshot chorioretinopathy are described. The patient was a 40-year-old woman. The condition can be treated with two types of medication, i.e., steroids and nonsteroidal anti-inflammatory drugs. Both appear to have a beneficial effect. Overall, however, the prognosis for this rare disease of unknown etiology remains uncertain. Given the slow progressive course, with spontaneous remissions and exacerbations, it is extremely difficult to evaluate the success of different forms of therapy. PMID- 2243478 TI - [Histopathology of the retina, optic fascicle and lateral geniculate body in chronic, bilateral symmetric ischemic Schnabel's cavernous optic atrophy]. AB - The paper is a unique pathological description of a bilateral, symmetric, anterior, temporal ischemic optic neuropathy with the morphological characteristics of cavernous optic atrophy initially described by Schnabel in glaucomatous eyes. The 80-year-old woman had suffered from cardiac insufficiency and diabetes mellitus for many years. She died from sepsis and circulatory collapse due to ischemic colitis, intestinal perforation, and peritonitis. There was widespread arteriosclerosis but no evidence of giant-cell arteritis. Cell loss was demonstrated in both retinas, the chiasm, and in the central lateral geniculate body. These represent a retrograde, descending and ascending optic atrophy, with transsynaptic degeneration in the LGB. A small craniopharyngioma was found by chance in the infundibulum. Neither clinically nor morphologically were there any signs of glaucoma. PMID- 2243479 TI - [Fundus hemorrhage in malaria tropica]. AB - The case is presented of a 20-year-old tourist with mild falciparum malaria and bilateral preretinal and intraretinal hemorrhage, including a macular hemorrhage with reversible visual loss, which developed during his return flight from West Africa. The diagnosis was initiated by the university eye hospital originally consulted. Possible pathogenic mechanisms, ocular findings in malaria, and the increasing problems of imported malaria are summarized and reviewed. PMID- 2243480 TI - [Bacterial pathogen and resistance spectrum of the non-irritated conjunctiva. 7,845 preoperative smears at the ophthalmologic clinic of the Erlangen university]. AB - The type and extent of bacterial colonization of the conjunctiva at the time of an intraocular operation may have a major influence on the risk of post-operative endophthalmitis. Between March 1986 and December 1988 a total of 7845 preoperative conjunctival smears were therefore examined by culture of Erlangen University Eye Hospital, in cooperation with the Department of Clinical Microbiology. Altogether, 1221 (15.6%) of the smears were classified as positive. Surgery on the patients concerned was postponed and gentamicin eye drops were administered for decontamination of their conjunctivae until the smears were negative. From the positive smears 1393 strains were cultured, identified, and submitted to a resistance test. The present paper reports the frequency distribution of the species of bacteria isolated and their resistance behavior, and compares the results with those of other authors. The value of preoperative cultures in the prevention of postoperative endophthalmitis and the importance of resistance tests in the context of topical application of antibiotics are discussed. PMID- 2243481 TI - [Laser therapy of diabetic maculopathy. A comparative study of the argon green laser and dye red laser]. AB - One hundred eyes with (pre)-proliferative diabetic retinopathy underwent central laser treatment for macular involvement. Fifty eyes were treated with the dye red 630 nm, the other 50 with the argon green 514 nm laser. Eighty of the eyes had previously undergone panretinal photocoagulation; in the other 20 this was performed 1.5-3 months after treating the macula because the central retinal changes were predominant. In accordance with the clinical angiographic classification of diabetic maculopathy, into an exudative, an edematous, and an ischemic type, three photocoagulation techniques were employed as appropriate, i.e., focal coagulation, (modified) grid coagulation, and extensive centripetal panretinal coagulation. Neither postoperative visual acuity, nor the fluorescein angiogram, nor fundus color photography revealed any significant difference in the results obtained with the two laser wavelengths. PMID- 2243483 TI - [Ophthalmopathologic findings in bog victims]. AB - More than 1800 corpses found in European bogs have been described. Most were found in northwest Germany and Denmark. The 2700-year-old corpse of a young woman found in the Borremose fen in Denmark is described. The face was crushed, though injury during cutting of the peat was ruled out. Light and scanning electron microscopy revealed vessels both in the choroid of one eye and in one ear, with intravascular corpuscles--probably erythrocytes--but no extravascular hemorrhage. This means that the face was almost certainly crushed post mortem and during the winter. The cause of death is unknown. Very few of the other bog finds in Europe are well preserved, and even fewer have been pathologically studied or radiocarbon-dated. Interpretation of their fate is a very difficult, complex problem. One reason for this is that the corpses often remained buried for several thousand years, and they are often poorly preserved. The first descriptions of it were Roman, in particular Tacitus' Germania, which appeared in 98 AD--it is thus much younger than most of the corpses so far found. Tacitus talks of hanging, drowning, and ritual sacrifices. As regards future bog finds, it is suggested that an archaeologist, an anthropologist, a forensic expert and a taxi-dermist should be called in as soon as excavation begins. International cooperation between experts could prove very fruitful. PMID- 2243482 TI - [Pre- and postoperative non-contact tonometry]. AB - The AO II non-contact tonometer (NCT) was compared with the Goldmann applanation tonometer (GAT) in 50 patients preoperatively and on the first day after cataract surgery. After pooling the preoperative and postoperative values, the relationship between NCT (y axis) and GAT (x axis) was described by the following regression: y = 1.01x - 0.69, where 1.01 is the slope and -0.69 (in mm Hg) is the y intercept of the regression line. The standard deviation (SD) in relation to the regression line was 2.19 mm Hg (y values). After separating the preoperative (n = 100; pressure range 6-21 mm Hg) and postoperative values (n = 47; pressure range 6-30 mm Hg) the following equations were obtained: preoperatively: y = 0.89x + 0.82 (SD 2.2 mm Hg); postoperatively: y = 1.06x - 1.15 (SD 2.24 mm Hg). Since the postoperative regression line comes close to that required for legal verification, the NCT may - with limitations - also be recommended for measuring IOP after cataract surgery. Both preoperatively and postoperatively, a significantly linear relationship was found between corneal thickness and the difference GAT minus NCT readings. This implies that in normal eyes with thin corneas the NCT tends to underestimate IOP, while in eyes with thick corneas there is a tendency to overestimate IOP. Even slight corneal edema (postoperatively) reduces this effect. PMID- 2243484 TI - [Color vision of animals. Views from Carl von Hess to today]. AB - In 1912 Carl von Hess, Professor of Ophthalmology in Munich, published the first comprehensive monograph on color vision in animals. He concluded that fish and all invertebrates are color-blind. At the same time, Karl von Frisch demonstrated that fish and honeybees can see and distinguish colors. The theory of trichromacy (Young-Helmholtz) is valid only for primates and some (e.g., bees) but not all insects. Almost all animals can see colors, and the eyes of some invertebrates contain up to 11 types of spectrally different receptor cells. Most animals - with the exception of mammals and cephalopods - can see ultraviolet and/or far red light. Therefore, many animals perceive more colors than human beings. PMID- 2243486 TI - Fictive ills: literary perspective on wounds and diseases. PMID- 2243487 TI - The great empty cup of attention: the doctor and the illness in the Wings of the Dove. AB - James confers on his characters his deepest fears and truths. He incorporates within his writing both his stunning and at times crippling intellectual powers and his dark inchoate mournful passion and remorse. The very events that made him a casualty are the experiences he grants to his characters to endure, to grapple with, and to master. In Wings James settles with his characters and with his readers the effects of these two deaths in his life. He was flattened by Minny's and Fenimore's deaths. He, like Marcher, cannot grasp the extent of his paralysis. It dawns on him like the sadness of a winter dawn but also like the explosive epiphany of Marcher at the grave that he has not lived. The words of Howell quoted by Sturges, the events of Wings, The Ambassadors, "The Beast in the Jungle" all reinforce what he knows to be true. He has not lived, he has not had what that man had to make him, by the loss of it, so bleed and yet live. What, after all, is more important in any life than the ability to love and the capacity to face death? This is the heart of the matter that James takes on in Wings. In the structure of the novel, to become conscious is to be in danger. Milly, the patient, achieves what eludes the other characters. Kate, Maud, Densher, Susan all are unable to raise their heads above their own lives. Only Milly is aware of herself within and beyond the book. Perhaps Densher begins in the very end to raise his head similarly, and in the sequel of "Beast," he achieves it.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243485 TI - Illness and exile: Sophocles' Philoctetes. PMID- 2243488 TI - Philoctetes' wound. PMID- 2243489 TI - Fierce privacy in the Wings of the Dove. PMID- 2243491 TI - The wisdom of pain: a responsive reading. PMID- 2243492 TI - The whole story. PMID- 2243493 TI - Death labors. PMID- 2243494 TI - His and hers: mental breakdown as depicted by Evelyn Waugh and Charlotte Perkins Gilman. PMID- 2243495 TI - Madness and medicine: the graphomaniac's cure. PMID- 2243496 TI - John Donne as a patient: Devotions upon Emergent Occasions. PMID- 2243497 TI - Distance on the look of death. PMID- 2243499 TI - Disease and cure in "Janet's Repentance": George Eliot's change of mind. PMID- 2243500 TI - Disease as device: the role of smallpox in Bleak House. PMID- 2243501 TI - Bleak House: the social pathology of urban life. PMID- 2243503 TI - Specific in vitro amplified probe detects the E2A gene rearrangement in the t(1;19) acute lymphoblastic leukemia. AB - Molecular studies have recently demonstrated that the E2A transcription factor gene was consistently located on chromosome 19 at the breakpoint of the 1;19(q23;p13) translocation, which characterizes a number of leukemias harboring a pre-B cell phenotype. Using a specific E2A gene probe spanning the DNA binding and dimerization domain obtained by PCR methodology, we were able to detect the rearrangement of the E2A gene in four cases (three patients and one cell line) of pre-B acute lymphoblastic leukemia with t(1;19) translocation. PMID- 2243504 TI - Chromosomal translocation t(14;19) as indicated by bcl-3 rearrangement is a rare phenomenon in non-Hodgkin's lymphoma and chronic lymphocytic leukemia: a molecular genetic analysis of 176 cases. AB - Using a probe for the newly described bcl-3 gene near the breakpoint of the t(14;19), 176 cases of non-Hodgkin lymphoma and B cell chronic lymphocytic leukemia were analyzed. Rearrangement of the bcl-3 gene was found in only one case; a follicular lymphoma involving the salivary gland that had progressed to a diffuse large cell lymphoma. We conclude that rearrangement of the bcl-3 gene as detected by our method occurs rarely in mature B or T cell neoplasms. PMID- 2243502 TI - Induction of genes for transcription factors by normal hematopoietic regulatory proteins in the differentiation of myeloid leukemic cells. AB - Induction of differentiation to macrophages in two different clones of myeloid leukemic cells by the hematopoietic regulatory proteins interleukin-6 (IL-6), or by granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL 3), is shown to be associated with sustained accumulation of c-jun, jun-B, and c fos mRNA that code for proteins that form complexes that are transcription factors (AP-1). In one but not in the other of these leukemic clones, differentiation is also associated with sustained accumulation of mRNA for the putative transcription factor zif/268. The results indicate that differentiation of myeloid cells by normal hematopoietic regulatory proteins is associated with induction of sustained elevated levels of mRNA for transcription factors that can regulate and maintain gene expression in the differentiation program, and that zif/268 gene expression is not essential for differentiation to macrophages. PMID- 2243505 TI - Intracytoplasmic detection of the Tac (p55) chain of interleukin-2 receptor in pre-B leukemic cells associated with a constitutive expression of Tac mRNA. AB - The pre-B Reh-6 leukemic cells do not express membrane interleukin-2 (IL-2)-R alpha (Tac or p55) chain; however, their incubation with PMA induces the expression of both high and low affinity IL-2-R. Northern analysis of nonstimulated Reh-6 as well as leukemic cells from patients with acute B cell precursor lymphoblastic leukemia displayed a constitutive expression of p55 mRNA transcripts, which could be enhanced by PMA. Both actinomycin-D and cycloheximide could abrogate PMA-induced p55 membrane expression, suggesting the need for de novo mRNA and protein synthesis. The increased PMA-induced p55 mRNA accumulation was an early event (4 hr) and could be enhanced, specifically, by rIL-2 because anti-Tac moAb inhibited this rIL-2-mediated effect. Immunofluorescence and cross linking studies using 125I-rIL-2 failed to reveal membrane-associated p55 protein on both Reh-6 and patients' leukemic cells. Conversely, immunogold staining and electron microscopy studies, revealed p55 immunoreactive molecules in the cytoplasm but not in the nucleus of all Reh-6 cells. Using a sensitive EIA, p55 molecules could be detected in cell lysates but not the culture supernatants of Reh-6 cells, suggesting that p55 was not released into the culture medium. These results indicate that constitutively expressed p55 mRNA on pre-B leukemic cells is translated into a relative immunoreactive protein that cannot be expressed on cell surface for unknown, yet, reasons. PMID- 2243506 TI - Kinetic rationale for cytokine-induced recruitment of myeloblastic leukemia followed by cycle-specific chemotherapy in vitro. AB - In patients with acute myeloblastic leukemia incomplete response to induction chemotherapy and short disease-free survival may be related to cell kinetic quiescence of leukemic cells. In this in vitro study, we tested the hypothesis that treatment with cytokines and subsequent chemotherapy (ARA-C, daunorubicin) can increase proliferation and enhance leukemic cell kill. We evaluated the effects of recombinant human interleukin-3 (rh-IL-3), granulocyte-macrophage colony stimulating factor (rhGM-CSF) and granulocyte colony stimulating factor (rhG-CSF) alone and in combination on AML (N = 11) and blastic phase CML (N = 3) samples. Cellular DNA and RNA, incorporation of bromodeoxyuridine (BrdU), cell growth fraction, cell viability, and differentiation markers were evaluated in vitro. A decrease of the quiescent cell population (p = 0.003) and an increase in S-phase cells (p = 0.001) was observed in 8/11 AML samples treated with cytokine combinations. Pronounced heterogeneity or proliferative response was seen between individual cases and different cytokines, but in the majority of the samples IL-3 was most effective. Significantly increased Ki67 expression (p = 0.009) and BrdU incorporation (p = 0.01) were also found after exposure to cytokines indicating an increase in growth fraction. DNA synthesis time was unaffected. Eight samples of AML were treated for 24 hr with ara-C following 2 days of in vitro cytokine incubation. Evaluation of leukemic cell kill showed increased cytotoxicity in three of those five samples which had significant depletions of G0 cells and increases in S-phase. None of the leukemic samples without recruitment from G0 had an increase in ARA-C cytotoxicity. This study provides detailed cell kinetic analysis of cytokine effects on AML blasts and provides a rationale for a novel approach to the treatment of AML. PMID- 2243507 TI - A phase I study of intermittent continuous infusion high dose cytosine arabinoside for acute leukemia. AB - We previously administered ara-C at a dose rate of 250 mg/m2/hr for 36-72 hr to patients with leukemia. Gastrointestinal toxicity was dose-limiting. This regimen was modified to an every other day schedule, administering 24-hr periods of high dose continuous infusion ara-C, each followed by a 24-hr rest period. Sixteen patients with relapsed/refractory acute myeloid leukemia (AML) (N = 4), secondary AML (N = 2), relapsed/refractory acute lymphoblastic leukemia (N = 7), or CML in blast crisis (N = 3) received this regimen of three 24-hr infusions with two intercurrent 24-hr rest periods. Grade 3 gastrointestinal toxicity was encountered in 57% of the courses, and hypoplasia was achieved in all patients. Three of the patients died while hypoplastic, two with septicemia and another with intracranial hemorrhage. There were five responding patients (2 CRs, 3 PRs). Median steady-state plasma ara-C levels were 24 microM, 22 microM, and 20 microM during the first, second, and third 24-hr infusions, respectively. Ara-C levels ranged from 4-118 microM during the infusions and were always below 4.5 microM during the rest periods. A significant level of ara-C incorporation into DNA was detected in each of the five patients studied, thus demonstrating that (ara-C)DNA formation is detectable in blasts from patients receiving high dose continuous infusion ara-C therapy. These findings suggest that alternate day continuous infusion ara-C may be useful in the treatment of acute leukemia and CML in blast crisis. PMID- 2243509 TI - DNA-fingerprint changes compared to karyotypes in acute leukemia. AB - Chromosomal analysis is routinely used in follow-up studies of acute leukemia, but it cannot be used in patients who do not have karyotypic abnormalities in blastic phase (10-46% of all cases). Recently we have demonstrated that unspecific DNA-fingerprint (DNA-F) changes can be detected in blastic phase of leukemia by DNA-F analysis. These changes can be used as molecular markers of the disease and in the follow-up studies of acute leukemia karyotyping and DNA-F analysis are complementary. The comparative analyses of leukemia samples with both these methods could help to localize minisatellite loci in chromosomes and reveal new DNA areas related to leukemia. New, more specific probes targeted to specific chromosomes could consequently be developed. We compared the DNA-F to the karyotypes of 50 acute leukemia patients. In blastic phase, 19 patients had DNA-F alterations and 31 patients abnormal karyotypes, 12 patients had both DNA-F alterations and karyotypic abnormalities. DNA-F changes were detected in six of the 16 patients with normal karyotypes and 19 patients with normal DNA-F had abnormal karyotypes at the time of diagnosis. Eleven patients showed neither DNA F changes nor abnormal karyotypes in blastic phase. Three acute myeloid leukemia (AML) patients with DNA-F changes in blastic phase had trisomy eight as a sole abnormality or combined with balanced translocation, which suggests that there might be AML associated minisatellite locus in chromosome 8. In other cases the karyotypes were complicated and no clear evidence of the relationship of DNA-F changes with other chromosomes could be found. PMID- 2243508 TI - Isotype switch and idiotype variation in hairy cell leukemia. AB - Hairy cell leukemia (HCL) cells are B lymphocytes expressing monoclonal surface bound immunoglobulins, B cell specific antigens, and activation markers. Based on immunophenotyping analysis, HCL cells have been reported to express simultaneously multiple Ig heavy chain isotypes. This is in contrast with the majority of other B cell malignancies. To analyse the tumor cell Ig in more detail, we have prepared somatic cell hybridomas from two patients with HCL. In both cases we found that the tumor cell derived hybridomas secreted IgM, IgG, or IgA indicating that a class-switch event does occur within the monoclonal tumor cell population. However these hybridomas expressed only single isotypes. The clonal relatedness of the tumor-derived Ig was shown by Ig gene analysis and by reactivity with a panel of idiotype specific antibodies. The tumor Ig of one patient analysed showed a striking variability in idiotope expression, indicative of somatic mutations of the expressed Ig genes. To our knowledge this is the first example of HCL and of a B cell malignancy other than follicular lymphoma for which somatic mutations have been demonstrated. This finding might be important for the therapeutic approach based on monoclonal anti-idiotype antibodies. PMID- 2243510 TI - Clinical applications of 3'-azido-2',3'-dideoxythymidine (AZT) and related dideoxynucleosides. PMID- 2243511 TI - 5-HT3 receptors. PMID- 2243512 TI - New developments in drug delivery systems. AB - The rate-controlled drug delivery systems outlined above have been steadily introduced into the biomedical community since the middle of the 1970s. It is the author's belief that many more of the conventional drug delivery systems which we have been using for many decades will be gradually replaced, in coming years, by these high-tech-based rate-controlled drug delivery systems. PMID- 2243513 TI - Potent inhibitors of de novo pyrimidine and purine biosynthesis as chemotherapeutic agents. PMID- 2243514 TI - Family cancer syndrome: a study of the kindred of a man with osteogenic sarcoma of the mandible. AB - Several familial cancer syndromes have been identified. The syndrome of sarcomas, breast cancer and other neoplasms, known as Li-Fraumeni syndrome, is characterized by several different neoplasms presenting at young ages with autosomal dominant transmission and a high incidence of second primaries. In this paper, we studied six generations (51 people) of the family of a 24-year-old man with osteogenic sarcoma of the mandible. Twelve malignancies in 11 people, including several rare tumors, were revealed. Mean age of presentation was 24 years old. Nine of the 11 patients died of disease. One developed a second primary. Two tumors presented in the head and neck. Transmission was autosomal dominant. The karyotypes of two family members were normal. Identification of Li Fraumeni syndrome in a family is important in determining appropriate follow-up for the patient and family. Such families are models for studying carcinogenesis. PMID- 2243516 TI - The surgical management of chronic parotitis. AB - Chronic parotitis is a disorder characterized by recurrent painful swelling of the gland with purulent sialorrhea. Occasionally, the condition fails to respond to medical management and definitive surgical therapy is necessary. Sialolithiasis is the usual etiology in cases of parotitis, although occasionally severe recurrent parotid infections are superimposed on underlying Sjogren's disease. Total parotidectomy with facial nerve dissection has been used in such cases in our department and has proved to be an excellent way to manage this disease. A summary of our results indicate that the recurring infections were eradicated and that the complication rate is tolerable, considering the magnitude of the problem. We feel that it is better to use surgical management early rather than wait for the formation of fistulae or abscesses. PMID- 2243515 TI - Gadolinium-enhanced magnetic resonance imaging in Bell's palsy. AB - Inflammation of the facial nerve in Bell's palsy can be demonstrated on gadolinium-enhanced magnetic resonance imaging. We have studied a series of 17 Bell's palsy patients with gadolinium-enhanced magnetic resonance imaging, and the purpose of this paper is to report our findings and discuss their significance. Most acute Bell's palsy cases demonstrate facial nerve enhancement, usually in the distal internal auditory canal and labyrinthine/geniculate segments. Other segments demonstrate enhancement less often. Gadolinium enhancement occurs regardless of the severity of the paralysis and can persist after clinical improvement of the paralysis. The findings of this study corroborate other evidence that the segments of the facial nerve most often involved in Bell's palsy are the only segments that are most often enhanced with gadolinium-enhanced magnetic resonance imaging. The role of gadolinium-enhanced magnetic resonance imaging in the management of Bell's palsy patients is discussed. PMID- 2243517 TI - Small fenestra stapedotomy using a fiberoptic hand-held argon laser in obliterative otosclerosis. AB - Obliterative otosclerosis has been a challenge since the advent of stapes surgery. "Drill-out" procedures have had a generally poorer prognosis than conventional stapes surgery because of excessive bleeding, acoustic trauma from the burr, and reclosure of the oval window by otosclerosis. In this report, we describe our early experience using a hand-held fiberoptic argon laser for small fenestra stapedotomy in 10 cases of obliterative otosclerosis. Closure of the air bone gap to within 10 dB was seen in 100% of the patients. There was no significant sensorineural hearing loss, vertigo, or facial weakness. Argon-laser stapedotomy using a hand-held fiberoptic system is a safe and effective alternative to drill-out stapedotomy in cases of obliterative otosclerosis. PMID- 2243518 TI - Avoiding a wrapped endotracheal tube in laser laryngeal surgery: experiences with apneic anesthesia and metal laser-flex endotracheal tubes. AB - Ninety-one laser laryngeal procedures using the apneic technique of anesthesia were performed in 28 patients between 2 months and 64 years of age. Seventy-two procedures (79%) were performed on children and 19 on adults. There were no complications. Eight laser laryngoscopies were performed using a new metal Laser Flex endotracheal tube. Obstruction of the endotracheal tube with a mucous plug occurred in one case. The apneic technique described in this paper provides a laser operative field free of an endotracheal tube, virtually eliminating the danger of a laser fire. It is a relatively safe and effective means of performing laser laryngeal surgery. In addition, the Laser-Flex endotracheal tube appears to be an acceptable alternative to a metallic tape-wrapped endotracheal tube. PMID- 2243520 TI - Chondrogenic potential of tragal perichondrium: a cause of hearing loss following stapedectomy. AB - Tragal perichondrium is a widely used tissue seal in the oval window following stapes surgery. Autogenous and easily accessible, it is a suitable substance to cover the vestibule in total stapedectomy, and to seal around the prosthesis in small-fenestra stapedotomy. The incidence of complications from the use of perichondrium in this manner is exceedingly low. We report a case where tragal perichondrium in the oval window resulted in the proliferation of cartilage. The cartilage displaced the stapes prosthesis, resulting in a conductive loss. Although the chondrogenic potential of perichondrium is known, we are not aware of other reports implicating this as a cause of failure in stapes surgery. The pertinent clinical and experimental literature regarding chondrogenesis is reviewed. This information suggests that the formation of cartilage from perichondrium in the oval window might be influenced by mechanical trauma and tissue orientation. PMID- 2243519 TI - Pediatric penetrating head and neck trauma. AB - Penetrating head and neck trauma in children causes uncommon and potentially life threatening injuries. We reviewed the charts of 21 patients who sustained penetrating injuries to the face or upper neck. Seventeen males and 4 females, aged 32 weeks' gestation to 19 years (mean = 10.2 years) comprised the study population. There were 15 gun-shot wounds, 1 shotgun injury, and 5 stab wounds. Significant problems included 7 vascular injuries, 6 central nervous system injuries, 5 ocular injuries, 3 airway compromises, 2 facial nerve injuries, 1 cervical esophageal penetration, and 2 cases of pneumothorax. Three deaths occurred, but the majority of the patients survived and sustained minimal permanent disability. Included in this review is a unique case of an intrauterine gunshot wound to the face at approximately 32 weeks' gestation. The treatment protocol, differences from adult patients, and management highlights are reviewed. PMID- 2243521 TI - The use of gadolinium-enhanced magnetic resonance imaging to determine lesion site in traumatic facial paralysis. AB - Gadolinium-enhanced magnetic resonance imaging has been used to evaluate 20 patients with surgically confirmed facial nerve lesions. When the nerve could be seen, gadolinium-enhanced magnetic resonance imaging accurately revealed the lesion site as well as the known extent, which in some cases was not predicted by topognostic testing. This technique appears to provide accurate lesion-site testing and may have importance in surgical planning. Currently used topognostic tests of facial nerve function are frequently inaccurate and can only determine the most proximal lesion site when there are multiple or extensive lesions. The focal nerve enhancement seen in nerve injury, globally increased signal intensity within the temporal bone after trauma, and increased signal intensity within the dura after surgery can occasionally mask nerve lesions and may be confused with tumors. PMID- 2243522 TI - Chondrosarcoma of the head and neck. AB - Chondrosarcoma is a malignancy rarely encountered in the head and neck. In an attempt to define this tumor's characteristics and response to therapy, all cases of chondrosarcoma treated at the University of Michigan over the past 25 years were retrospectively studied. Fourteen cases originating in the nose and paranasal sinuses, mandible, temporal bone, and larynx were reviewed. Aggressive surgical resection was the mainstay of treatment, and resulted in an overall survival of 70%, with an average follow-up of 3.5 years. Survival was highest in primary temporal bone lesions, and lowest in paranasal sinus lesions. Unresectable lesions were not cured by other modalities. This study, therefore, continued to support the crucial role of wide surgical resection in the treatment of head and neck chondrosarcoma, but conservative resection, when needed to preserve important structures, has resulted in long-term survival. PMID- 2243523 TI - Selective management of early glottic cancer. AB - Seventy patients with stage I and II glottic cancer were treated at the University of Utah School of Medicine hospitals from 1980 through 1987. Forty four patients had stage I cancer and 26 patients had stage II. The overall survival in the stage I group was 82%. Primary site control was 93% with only three deaths due to laryngeal cancer. Local control rates were 93% with CO2 laser excision, 80% with CO2 laser and irradiation, and 67% with radiation alone. Stage II glottic patients had an overall survival of 61.5% with a local control rate of 76%. Twenty-one of 24 patients were treated by full-course irradiation. Of the eight patients who recurred at the primary site, all were irradiation failures who had initial bulky disease and impaired vocal cord mobility. Selective CO2 laser excision was highly effective, whereas radiation therapy results were somewhat disappointing. Open partial laryngectomy should be considered in bulky stage II disease patients. PMID- 2243524 TI - The melanocyte and melanoma. AB - This paper reviewed some of the interesting biological aspects of melanocytes and their relationship to the nevus and to melanoma. It also proposed a rationale for "adequate" surgery in the management of melanoma according to level, depth, margins, and trends in treatment. These propositions were derived from an analysis of 995 cases of melanoma of the head and neck. PMID- 2243525 TI - Allograft tympanoplasty: predictive value of preoperative status. AB - The functional and anatomical results of a series of 181 consecutive allograft tympanoplasties for ears with drum perforation and an intact ossicular chain were retrospectively reviewed and related to preoperative factors. Drum closure was realized in 92% (166 of 181 cases evaluated 1 year after surgery), and 96.6% of the reconstructed drums were still intact 3 years after surgery (118 cases evaluated). An air-bone gap of less than 21 dB was reached in 79.6% (of a total of 162 cases) 1 year after surgery, and in 78% (of a total of 118 cases) 3 years after surgery. Age, contralateral pathology, the wet or dry status of the ear preoperatively, and the preoperative air-bone gap had no influence on anatomical results. The preoperative air-bone gap did not predict the postoperative air-bone gap. The influence of age and existence of contralateral pathology on hearing gain was only visible in some of the strictly defined patient groups. The wet preoperative status of the ear generally predicted lower functional gain. PMID- 2243526 TI - Computer-aided three-dimensional reconstruction and measurement for multiple electrode cochlear implant. AB - To assist surgeons in performing multiple-electrode cochlear implant operations, the spatial relations between middle and inner ear structures in six normal temporal bones were studied using the computer-aided 3-D reconstruction method. When viewed through the external auditory canal, the approach used for electrode insertion, and the relation of the malleus to the helicotrema or the scala vestibuli in the second turn of the cochlea were found to vary considerably. In contrast, when viewed from the same transmeatal approach, both the direction and the distance from the stapes footplate to the scala vestibuli of the second turn of the cochlea and helicotrema were found to be quite stable. We concluded that the stapes footplate was a better landmark than the malleus when approaching the helicotrema and scala vestibuli of the second turn of the cochlea during multiple electrode cochlear implant surgery. PMID- 2243527 TI - A palmar dermatosis linked to occult carcinoma of the upper thorax, head and neck: Bazex's syndrome and tripe palm. AB - An unusual, persistent, corregated-to-honeycombed thickening of the palms accompanied by tenderness around the fingernails was found to be a cutaneous marker for internal malignancy. This combination of signs and symptoms has been reported under two clinical entities: Bazex's syndrome and tripe palm. This paraneoplastic syndrome is of interest to head and neck surgeons due to the location of the primary tumor, the site of metastatic disease, and the ability to cure the cutaneous disease by surgical removal of the primary tumor. In our patient, a squamous cell carcinoma of the lung not detectable on chest x-ray presented as a cervical mass accompanied by cutaneous changes on the palms and fingernails. Recognition of the relationship of the dermatologic changes to malignancy of a specific body region eventually led to the detection of the primary tumor. The characteristics of these paraneoplastic syndromes were reviewed in this report. PMID- 2243528 TI - Otologic disease in AIDS patients: CT correlation. AB - The contrast-enhanced computed tomographic (CT) scans of the temporal bone and brain in 18 patients with otologic disease and acquired immunodeficiency syndrome (AIDS) were retrospectively reviewed. Seven scans revealed middle ear and mastoid disease; three scans were consistent with central nervous system (CNS) pathology; and eight scans demonstrated no abnormalities. CT scanning was found useful in localizing otopathology and diagnosing CNS toxoplasmosis, aural polyps, osteomyelitis, mastoiditis, and middle ear effusion due to hypertrophic lymphoid tissue. The authors conclude that AIDS patients with sensorineural hearing loss should undergo contrast-enhanced brain CT scans to rule out CNS pathology; AIDS status does not alter criteria for CT scanning in patients with conductive hearing loss; and that images of the nasopharynx should be included on temporal bone CT scans of patients with conductive hearing loss in order to exclude eustachian tube obstruction by hypertrophic lymphoid tissue. PMID- 2243529 TI - Isolated congenital stapes ankylosis: surgical results in 32 ears and a review of the literature. AB - Isolated congenital stapes ankylosis is described in 32 operated ears from 28 patients. In 27 ears, a regular stapedectomy was performed. In the remaining 5 ears, 2 had stapes gushers, 2 had bony stapedial tendons, and 1 had an aberrant facial nerve crossing the oval window. The average individual hearing gain was 20 dB. The mean hearing gain for the 24 successful stapedectomies was 29 dB. In 24 of 32 ears (75%), an essential hearing gain of at least 15 dB Fletcher's index hearing threshold could be achieved. A Fletcher's index not exceeding 30 dB could be achieved in 19 of 32 ears (60%), in spite of several cases with a sensorineural component in the hearing loss. A review of the literature and overview of longer series with isolated congenital stapes ankylosis is presented. PMID- 2243530 TI - A comparison of class II antigenicity of human tracheal allografts stored in cialit and in merthiolate. AB - This report deals with some of the immunological aspects of the transplantation and preservation of human tracheal grafts. The immunological behavior of the transplanted graft depends largely on the interaction of the preservatives with the tissue proteins. Using monoclonal antibodies and the immunoperoxidase staining technique we have investigated the effect of Merthiolate, Cialit, formaldehyde/Merthiolate, and formaldehyde/Cialit preservation techniques on monomorphic determinants of class II transplantation antigens in human tracheal allografts. Unpreserved grafts were found to express class II antigens. These antigens were totally destroyed after 7 days in formaldehyde and 42 days in Cialit and Merthiolate. Preservation in Cialit and Merthiolate showed a gradual disintegration of the histological structures. In contrast, buffered formaldehyde did not appear to alter the histological structure of the tracheal graft. Irrespective of the mode of preservation, the cartilaginous tissue appeared to persist virtually unaffected. No essential differences were observed between the immunological staining of tracheal grafts preserved in Cialit and Merthiolate. PMID- 2243531 TI - The inferiorly based superior tympanomeatal flap for removal of congenital cholesteatoma. AB - We believe that the IB-STMF is preferable to the P-TMF for removal of a congenital cholesteatoma from the anterior superior portion of the mesotympanum. Though developing an IB-STMF may require extra time and special care to avoid tearing the flap, the exposure that is achieved affords the best chance for complete removal of the mass, thus decreasing the chance for persistence or recurrence of the lesion. PMID- 2243532 TI - The endoscopic approach for revision dacryocystorhinostomy. PMID- 2243533 TI - Severe epistaxis: protecting the nasal ala. PMID- 2243534 TI - Effect of alpha interferon on glucose and alanine transport by rat renal brush border membrane vesicles. AB - To investigate the pathogenetic mechanisms of interferon nephrotoxicity, we studied the effect of recombinant interferon alfa-2b on the uptake of 14C-D glucose and 14C-L-alanine by rat renal brush-border-membrane vesicles. Interferon significantly inhibited 20 sec. sodium-dependent and 5 and 10 min. equilibrium uptake of both glucose and alanine. The inhibitory effect was dose dependent with maximum effect achieved at interferon concentration of 5 X 10(-8)M in the uptake media. The half-maximal inhibitory concentrations, IC50, of interferon on glucose uptake was 1.8 X 10(-8)M, and 5.4 X 10(-9)M on alanine uptake. Dixon plot analysis of uptake data was consistent with pure non-competitive inhibition. The inhibition constants, Ki, 1.5 X 10(-8)M for glucose uptake, and 7.3 X 10(-9)M for alanine uptake, derived from Dixon plots were in close agreement with the IC50s calculated from the semilog dose response curves. These observations reveal that direct interactions at the proximal tubule cell membrane are involved in the pathogenesis of interferon nephrotoxicity, and that its mechanism of nephrotoxicity is similar to that of other low molecular weight proteins. PMID- 2243535 TI - Different turnover of rat fetal and placental ornithine decarboxylases. AB - The half-lives of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) have been studied in fetuses and placentas from 18-day pregnant rats. While the turnover of fetal and placental SAMDC were slightly different (t1/2 = 38 and 75 min, respectively) the half-lives of fetal and placental ODC differed markedly. T1/2 of fetal ODC was 15 min, similar to other mammalian ODCs, but placental ODC showed a relatively high half-life, about 160 min. According to that, placental ODC was more resistant than the fetal enzyme to in vivo hyperthermic treatment (40 degrees C, 1 h). Our results suggest that the degradative mechanisms for ODC in rat placenta could be regulated differently to those in other mammalian tissues. PMID- 2243536 TI - Possible mechanism of gastric mucosal protection by epidermal growth factor in rats. AB - The mechanism of the protection by human epidermal growth factor (hEGF) against the gastric mucosal lesions induced by acidified ethanol was studied in rats. At different times following the subcutaneous administration of hEGF (30 micrograms/kg), intragastric acidified ethanol (EtOH: 0.125 M HC1 = 50:50 v/v%) was administered to induce an experimental gastric mucosal lesion. Mean length of the lesion in the gastric mucosa was used as a lesion index. Extravasation of intravenously injected Evans blue into the gastric wall and gastric contents was used as an indicator of vascular permeability. Pretreatment with hEGF decreased both the gastric mucosal lesions and the increase of vascular permeability caused by acidified ethanol with similar time profiles relative to pretreatment with hEGF. Maximal protective actions of hEGF occurred about 10 to 30 min after the observed peak plasma concentration of hEGF. Indomethacin and N-ethylmaleimide, but not iodoacetamide, blocked the protective action of hEGF, indicating that endogenous prostaglandins and/or sulfhydryls may participate in the protective action of hEGF. The content of endogenous nonprotein sulfhydryls in the gastric mucosa decreased markedly after acidified ethanol. However, pretreated hEGF did not restore the sulfhydryl contents. Thus, it seemed that endogenous prostaglandins, but not sulfhydryls, are the probable mediators for protection against gastric mucosal injury caused by acidified ethanol. PMID- 2243537 TI - Elevated cytosolic calcium in cerebrocortical nerve terminals of rats during prolonged ethanol ingestion. AB - Increases in cytosolic free calcium concentrations ([Ca++]i) may underlie acute neuronal degeneration during ischemic or anoxic episodes, seizures and excitotoxin treatment. With quin-2 and fura-2 fluorescent probes, we have obtained evidence for elevated [Ca++]i in cerebrocortical terminals of adult rats following chronic consumption of ethanol-containing liquid diets for "neurotoxic" durations. Compared to isocaloric carbohydrate-fed controls, ethanol-fed rats had significantly higher [Ca++]i in P2 synaptosomal fractions after 4 months of diet intake, and in purified cerebrocortical synaptosomes after diet ingestion for 10 months. In addition, [Ca++]i in the synaptosomal fractions of ethanol-fed rats from either exposure time were markedly resistant to K(+)-dependent potentiation. Persistently increased synaptic [Ca++]i and a blunted response to K+ depolarization following chronic ethanol ingestion lead us to associate impaired Ca++ homeostasis in the neurodegenerative processes of alcoholism. PMID- 2243538 TI - In vitro vasoconstriction induced by calcium in renovascular hypertensive or old rats. AB - We studied the changes in calcium-induced vasoconstriction in isolated tail arteries from young (2 months) and old (12 months) normotensive, and young renovascular hypertensive rats (3 months old, with unilateral renal artery clipping at 6 weeks), pretreated with reserpine. The tail artery was removed and perfused/superfused with either a high potassium Krebs depolarizing solution or Krebs solution plus phenylephrine. Concentration-response curves to calcium were produced. Old rats had a low plasma renin activity and their depolarized tail arteries showed a weak vasoconstrictor response to calcium. Renovascular hypertensive rats had a high mean blood pressure and plasma renin activity. Responses of their depolarized tail arteries to calcium were greater. Responses to calcium in tail arteries perfused with phenylephrine were similar in all groups. We conclude that age and renovascular hypertension produce opposite changes in vasoconstriction induced by calcium in depolarized tail arteries. PMID- 2243539 TI - Estradiol processing by pituitary cells in culture: an examination of the influences of various exposures to progesterone. AB - Dispersed, estradiol (E2)-treated pituitary cells were used to examine the cellular mechanisms underlying progesterone (P) suppression of GnRH-stimulated LH and FSH secretion. When cells were exposed to 10(-9) M E2 for 48 h prior to GnRH challenge, P (10(-7) M) treatment for the last 24 h suppressed gonadotroph responsiveness to GnRH for both LH and FSH secretion (gonadotropin released/intracellular stores of gonadotropin available for release). To determine if P acts by blocking E2 processing and/or uptake, we exposed cells to 2,4,6,7-3H-E2 +/- P and monitored the level and distribution of 3H-estrogens bound to estrogen receptors salt-extracted from nuclear pellets purified by sucrose density centrifugation. At 1, 4 and 24 h, P had no effect on the level of 3H-estrogen+receptor complexes or on the distribution of receptor-bound 3H-E2, 3H estrone and 3H-estriol. The results indicate that chronic influences of P to suppress the responsiveness of E2-treated gonadotrophs to GnRH cannot be explained by alterations in estrogen receptor occupation as is the case in reproductive tract tissues. PMID- 2243540 TI - Differential effects of sex steroids on uterine and renal ODC activity in ovariectomized rats. AB - Many hormones are known to induce the activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme for polyamine biosynthesis, in their target tissues. Using ovariectomized rats, we have compared the effects of sex hormones on ODC activity in the uterus and the kidney which contain estrogen and androgen receptors. The results show that 1) both estrogen and androgen stimulate renal ODC activity, 2) estrogen but not androgen effectively increases ODC activity in the uterus, 3) estrogen at higher dosage can stimulate renal ODC activity to an extent similar to that in the uterus, 4) daily treatment with estradiol for 5 days results in the desensitization of uterine ODC activity, but not that of renal ODC activity to the hormonal stimuli. Although both uterus and kidney are targets of sex hormones, our results indicate that estrogen and androgen have differential influences on the ODC activity in these two organs. PMID- 2243541 TI - Buprenorphine-induced pupillary effects in human volunteers. AB - The pupillary effects of the partial opiate agonist buprenorphine were studied in 16 male subjects who were heroin dependent at the time of admission to the study. Sublingual buprenorphine (8 mg) was administered daily for 18 days and continued either daily or on alternate days from study days 19 through 36. On days 37 through 56, all subjects received buprenorphine placebo. Compared to placebo, buprenorphine decreased pupil size and diminished the constriction and dilation velocities of the light reflex. These effects occurred within 5 hours of buprenorphine administration. Following placebo administration during alternate day dosing of buprenorphine, pupil size increased and constriction and dilation velocities of the light reflex were significantly greater than after buprenorphine administration in the same subjects. This pattern of effects was observed after buprenorphine was discontinued (day 37). The results indicated that buprenorphine has pupillary effects like those of full opiate agonists. The time course of these effects was similar to previously-reported effects of buprenorphine on the electroencephalogram but not to the time course of subjective effects. PMID- 2243543 TI - A brief treatise on the academic committee. PMID- 2243542 TI - A microcomputer system for residents. PMID- 2243544 TI - The Cancer Prevention Reminder System. AB - The Cancer Prevention Reminder System is a computer-based system designed to increase the delivery of periodic health maintenance procedures. The program provides printed reminders that identify patients' overdue procedures, prints summary reports of the percentage of patients who are eligible and overdue for a procedure, and prints mailing labels for patients. We performed a randomized, controlled trial in which the effects of computer-based reminders were compared with those of two other interventions among residents in a university-based group practice. PMID- 2243545 TI - A computerized laboratory alerting system. AB - A computerized laboratory alerting system (CLAS) has been developed as part of an ongoing effort to improve the quality of care at LDS Hospital. The system identifies potentially life-threatening conditions on the basis of laboratory findings and then generates appropriate warnings and transmits them to clinicians. Use of the system has led to a significant increase in the proportion of patients in life-threatening situations who have received appropriate care (50.8% before implementation vs. 62.5% afterward, P less than 0.05). Among patients with hypokalemia, falling potassium levels, hyperkalemia, hypokalemia during treatment with digoxin, hyponatremia, falling sodium levels, hypernatremia, hypoglycemia, or hyperglycemia, the average length of time spent in the life-threatening situation has decreased from 30.4 to 15.7 hours (P less than 0.05) and the average length of stay has decreased from 14.6 to 8.8 days (P less than 0.05). There has been little change in the proportion of patients with findings indicating metabolic acidosis who have received appropriate care (32.3 vs. 34.6%). We conclude that CLAS has an important role in patient care at our hospital. PMID- 2243546 TI - Information retrieval in medicine: state of the art. AB - Conventional information retrieval systems usually involve searching by terms from controlled vocabularies or by individual words in the text. These systems have been commercially successful but are limited by several problems, including cumbersome interfaces and inconsistency with human indexing. Research on methods that automate indexing and retrieval has been performed to address these problems. The three major types of automated systems are vector-based, probabilistic, and linguistic. This article describes these systems and provides an overview of the field of information retrieval in medicine. PMID- 2243547 TI - Choosing the software for an office computer. PMID- 2243550 TI - Different drummers: Neil Pappalardo. PMID- 2243548 TI - Computer-based support for clinical decision making. AB - Although computers are now commonly used for financial purposes in hospitals and physicians' offices, most physicians do not routinely use them in patient care. And in hospitals where laboratory data are provided on computer terminals, the displays are often difficult to use and programs that offer assistance in interpreting the data are usually unavailable. We have developed decision support programs that are widely used with the clinical computing system at our hospital. This paper describes the programs and how the clinicians use them. PMID- 2243549 TI - An update on the resident office management program. PMID- 2243551 TI - Speech recognition as a user interface. PMID- 2243552 TI - Oxygen therapeutics. PMID- 2243553 TI - Choice of cephalosporins. PMID- 2243554 TI - Trends in lung cancer incidence and mortality--United States, 1980-1987. AB - Lung cancer is the most common fatal malignant neoplasm in the United States. Based on current smoking patterns, the substantial public health burden of smoking-related lung cancer will continue during the next several decades. This report describes trends in lung cancer incidence from 1980 through 1986 and lung cancer mortality from 1980 through 1987. PMID- 2243555 TI - Gallstone lithotripsy--ready or not? PMID- 2243556 TI - Assisted reproductive technologies at the UNC hospitals. An update. PMID- 2243558 TI - Congenital syphilis. Resurgence of an old problem. PMID- 2243557 TI - The child with a tracheotomy. A review of the surgical options in airway reconstruction. PMID- 2243559 TI - Reliving the early days of neurosurgery. PMID- 2243560 TI - Arthritis. PMID- 2243561 TI - Managed care contracts. Dangerous liaisons? PMID- 2243562 TI - Carolina Doctors Care IPO. PMID- 2243563 TI - Pain clinic looks at the "single digit sign". PMID- 2243564 TI - Two comments on Dr. Sanders's and Dr. Nemeroff's articles on prescribing addictive drugs. PMID- 2243565 TI - Renal response to ureteral obstruction in early development. PMID- 2243566 TI - Beta-2-microglobulin generation rate and clearance rate in maintenance hemodialysis patients. AB - We analyzed the rebound pattern of plasma beta 2-microglobulin (beta 2-m) concentration from 4 h after completion of hemodiafiltration until the start of the next treatment according to the one-pool beta 2-m kinetic model so as to determine beta 2-m generation rate and whole-body beta 2-m clearance. Next, we obtained the whole renal beta 2-m clearance as the product of renal creatinine clearance and the glomerular sieving coefficient of beta 2-m. Then, extrarenal beta 2-m clearance was calculated as the difference between whole-body beta 2-m clearance and whole renal beta 2-m clearance and renal beta 2-m clearance due to tubular absorption was taken to be the difference between whole renal beta 2-m clearance and renal beta 2-m clearance due to urinary excretion. The results showed that the higher the patients' plasma beta 2-m concentration was, the lower was the whole-body beta 2-m clearance. Moreover, in the present study, an inverse correlation was found between the following respective factors: plasma beta 2-m concentration and whole renal beta 2-m clearance; plasma concentration and renal clearance due to tubular absorption; plasma concentration and renal clearance due to urinary excretion. However, there was no correlation between plasma beta 2-m concentration and extrarenal beta 2-m clearance. The findings indicate that the variation of plasma beta 2-m concentration with the individual patient is solely attributable to the variation in residual renal function in terms of beta 2-m elimination. PMID- 2243568 TI - Hypertensive exercise responses in ciclosporin-treated normotensive renal transplant recipients. AB - Although many patients taking ciclosporin (CS) for the long term develop hypertensive side effects, a proportion do not. We have studied the blood pressure response to graded upright bicycle exercise while continuously recording the metabolic rate in 18 normotensive renal transplant recipients whose mean age was 30.8 years (range 16-54). Nine were treated with CS alone and 9 with azathioprine and a steroid, prednisolone (AzS). Both groups performed a progressive exercise test, with work increasing by 25 W every 4 min from rest. All patients completed a workload of at least 75 W during the test. A group of 8 normal subjects whose mean age was 29 years (range 19-44) were exercised with the same protocol. The CS group had a significantly higher mean systemic blood pressure at both 50 and 75 W (124 and 132 mm Hg, respectively), compared with the AzS group (103 and 108 mm Hg; p less than 0.01). The blood pressure response to exercise in the AzS group was similar to that observed in the normal group. This was despite a higher metabolic rate at each stage of work in the AzS group as compared with the CS or normal groups. Despite being normotensive at rest, renal transplant patients who are treated with CS have evidence of a vasopressor effect, with systemic vascular resistance inappropriately high for exercise, implying reduced compliance of the vascular bed. PMID- 2243567 TI - The renal hemodynamic response following a meat meal in children with chronic renal failure and in healthy controls. AB - The renal hemodynamic response to a meat meal (2 g/kg BW) was studied in 11 healthy children and in 10 children with a mean plasma creatinine concentration of 2.6 +/- 0.1 mg/dl due to chronic renal failure (CRF) of various etiologies. In the healthy status, after a meat meal, the glomerular filtration rate (GFR) increased significantly from a baseline value of 119.0 +/- 5.0 to a peak of 159 +/- 5.8 ml/min x 1.73 m2; in CRF baseline GFR averaged 49 +/- 4.0 and at peak 76.6 +/- 7.2 ml/min x 1.73 m2 (p less than 0.005). The peak GFR response was reached earlier in healthy subjects than in CRF (p less than 0.05) and did not correlate with age or with baseline GFR. Renal plasma flow (RPF) in healthy controls increased from 532 +/- 32 at baseline to 646 +/- 42.9 ml/min x 1.73 m2 after the meal (p less than 0.005). Also in CRF after a meat meal there was a significant increase in RPF from 278 +/- 51 to 65 +/- 66 ml/min x 1.73 m2 (p less than 0.005). The filtration fraction was not affected. The percent increase over baseline values of GFR and RPF at the peak was significantly higher in diseased children. Renal reserve averaged 28.1 +/- 5.3 ml/min in diseased children and 39.7 +/- 5.2 ml/min (p less than 0.01). The data indicate that (1) a meat meal is a suitable method to recruit renal reserve in normal children and in children with chronic renal failure, and (2) the renal reserve is normal in chronic renal failure. PMID- 2243569 TI - Kidney transplantation in systemic lupus erythematosus nephritis: a one-center experience. AB - Eight patients with end-stage renal disease secondary to systemic lupus erythematosus (SLE) received 8 cadaveric renal allograft. Patient and graft survival was 100 and 87%, respectively. None of them showed extrarenal manifestations of SLE or recurrence of lupus nephritis after grafting. One graft was lost because of chronic rejection. In another patient, an episode of graft function deterioration due to bad control of arterial hypertension was observed. Three patients were transplanted during their first year on hemodialysis. Two women became pregnant after successful kidney transplantation; one suffered a spontaneous abortion and the other had a successful delivery. In neither of them, was SLE observed during or after pregnancy. Morbidity was low in this series, and infections were the most frequent complication. In summary, our experience with renal transplantation in SLE patients compares, favorably with the general nodiabetic transplanted population. PMID- 2243570 TI - Soluble interleukin 2 receptor and tissue polypeptide antigen serum concentrations in end-stage renal failure. AB - Serum concentrations of soluble interleukin 2 receptor (IL-2R) were measured in 65 hemodialysis patients and compared with serum levels of beta 2-microglobulin and tissue polypeptide antigen (TPA). Elevated IL-2R levels, found in 85% of examined patients, correlated with elevated TPA serum concentrations (p less than 0.05). Patients with high IL-2R levels were significantly younger (p less than 0.05) than patients with low levels. Primary renal disease and residual renal function had no significant influence on TPA or IL-2R serum concentrations. In 16 patients with carpal tunnel syndrome, increased serum concentrations of IL-2R (p less than 0.005) and TPA (p less than 0.001) were found. We conclude that a non specific dialysis-induced activation of epithelial and lymphoid cells rather than a specific immune response could explain the concomitant elevation of IL-2R and TPA serum concentrations in hemodialyzed patients. Patients with pronounced cell turnover, reflected by elevated IL-2R and TPA levels, may show an increased susceptibility to dialysis-associated amyloidosis. PMID- 2243571 TI - Uremic serum inhibits monocyte-dependent, but not interleukin-2-dependent steps of T cell proliferation. AB - We examined the influence of uremic serum on antigen receptor triggered T cell proliferation in dialysis patients with impaired immune function, i.e., 12 nonresponders to hepatitis B vaccination. The dialysis patients showed a monocyte dysfunction and an increased responsiveness to interleukin 2 (IL-2) according to our previous findings. In vitro the addition of IL-2 completely reconstituted the defect. Uremic serum inhibited monocyte-dependent T cell proliferation of patients and of healthy controls. Contrary, monocyte-independent steps of T cell proliferation were not impaired by uremic serum. When IL-2 was added to cultures, the T cell proliferation in the presence of uremic serum was even enhanced. We conclude that uremic immunodeficiency may be enhanced by soluble factors present in uremic serum which inhibit monocyte-dependent steps of T cell proliferation. PMID- 2243572 TI - Paired filtration dialysis: optimizing depurative efficiency with separate convection and diffusion processes. AB - To overcome reciprocal interaction between convection and diffusion occurring in hemodiafiltration, we separated the two processes in a new dialysis technique called paired filtration dialysis (PFD). In this technique, convection and diffusion take place separately on two capillary membranes: a polysulfone hemofilter and a hemophan dialyzer. The depurative effectiveness of PFD with respect to small (blood urea nitrogen, creatinine, uric acid, phosphate) and large (beta 2-microglobulin) molecules was acutely assessed in 6 patients on maintenance acetate hemodialysis. Despite a 3-hour treatment time, a high mass removal of small and large solutes was found in PFD without high ultrafiltration rates or blood flows in excess of 300 ml/min. There was no significant difference in solute removal between the two different depurative sequences adopted in PFD, i.e., convection followed by diffusion or vice versa. A significant reduction in beta 2-microglobulin serum levels was observed in both PFD modes. Twenty patients, on a 12-month period of 3-hour PFD treatment, maintained an unaltered metabolic, clinical, and acid-base status, and cardiovascular stability was not affected. PFD thus provides excellent depurative results, along with simple technical features that are particularly useful in treating patients with high depurative needs and yet are unable to tolerate high-flux techniques. PMID- 2243573 TI - Effect of heparin and prostacyclin/heparin infusion on platelet aggregation in hemodialyzed patients. AB - The number of circulating platelet aggregates determined according to the method of Wu and Hoak and the platelet morphology revealed by scanning electron microscopy were investigated in 10 patients (8 males, 2 females) age 28-58 years) with end-stage renal failure treated by repeated hemodialysis. The examination was carried out twice: during a 4-hour hemodialysis session with the use of heparin alone and 1 week later during the course of another dialysis in the presence of both heparin and prostacyclin. During each dialysis session the platelet system was examined three times: prior to, after 90 min, and at the end of the procedure. As compared with the situation prior to dialysis, the number of platelet aggregates assessed after 90 min of dialysis and after its termination insignificantly rose following the treatment with heparin, but significantly fell after the use of the prostacyclin/heparin combination. The differences were also significant when the effects of both treatment types were compared. As revealed by scanning electron microscopy, during the course of hemodialysis with the use of heparin alone, the platelets showed signs of activation manifested by increases in number and length of cytoplasmic processes and by a tendency to aggregate. When both prostacyclin and heparin were used during dialysis, platelet activation was minimal or absent. Thus, the combined treatment with prostacyclin and heparin protects platelets from activation induced by their contact with artificial surfaces and may lower the risk of microthrombosis, making thereby hemodialysis safer and more effective. PMID- 2243574 TI - Zinc and copper metabolism in nephrotic syndrome. AB - The effect of proteinuria on urinary zinc and copper excretion was studied in children with nephrotic syndrome (NS). Clearance, fractional excretion, and urinary excretion of zinc and copper were significantly higher in children with relapse of NS than in the same children with remission of NS or in healthy children. A linear correlation was found between proteinuria and urinary zinc and copper excretion in relapse of NS. The results of this study suggest that zinc and copper deficiency in NS may be related also to increased urinary zinc and copper losses. PMID- 2243575 TI - Toxic acute renal failure and hepatitis after ingestion of raw carp bile. AB - The raw carp bile has both nephrotoxic and hepatotoxic effects which are not well known. Recently, we studied 13 patients who had toxic acute renal failure and toxic hepatitis after ingestion of raw bile of carp in 3, grass carp in 8 and silver carp in 2 cases. The purpose of this report is to alert physicians to this very rare cause of toxic acute renal failure and hepatitis. All patients presented initially with gastrointestinal upset after eating. These symptoms were followed by oliguria in 7 patients (54%), hematuria was noted in 10 (77%) and jaundice in 8 patients (62%). Elevation of blood urea nitrogen, creatinine and transaminases lasted for about 3 weeks. The severity of the symptoms depended on the amount of bile ingested. All the patients recovered with conservative therapy and hemodialysis. Biopsy of the kidney revealed findings compatible with acute tubular necrosis similar to that produced by other nephrotoxins. Biopsy of the liver revealed findings consistent with acute toxic hepatitis. Both suggest toxic effects of carp bile as a cause of toxic acute renal failure and hepatitis. PMID- 2243576 TI - Renal blood flow and glomerular filtration rate during the heterologous phase in passive Heymann nephritis in rats. AB - When passive Heymann nephritis (PHN) is induced by infusion of antibodies (anti Fx1A), an acute fall in renal blood flow (RBF) and glomerular filtration rate (GFR) has been reported. Activation of the complement cascade by the local antigen-antibody reaction might be involved in this reaction. We therefore studied RBF and GFR during acute infusion of anti-Fx1A and after 3 days when heterologous antibodies are no longer present in the circulation. Two groups of rats were infused with 2 mg anti-Fx1A antibodies into the left renal artery; RBF was measured by the microsphere method and GFR by 125I-Na-iothalamate clearance. In the first group, the measurements were made 40 min after the infusion, and in the second group after 3 days. A third group was studied 3 days after infusion of 1 mg anti-Fx1A. Animals infused with normal IgG were used as controls. Forty minutes after infusion of 2 mg anti-Fx1A, GFR in the left kidney was reduced from 1.16 +/- 0.07 to 0.41 +/- 0.16 ml/min/g in the controls (p less than 0.05). Three days after the infusion, GFR was 1.04 +/- 0.07, not significantly different from control. RBF was reduced to 3.97 +/- 1.11 ml/min/g after 40 min, compared to 7.53 +/- 0.73 in controls (p less than 0.05), and was normalized after 3 days. The effect of 1 and 2 mg anti-Fx1A antibodies was not significantly different after 3 days. Anti-Fx1A antibodies were detected in serum in the acute stage, but not after 3 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243577 TI - Effect of drug additives to peritoneal dialysis solutions on the viability and function of mouse peritoneal cells. AB - Peritoneal dialysis (PD) solutions and therapeutic drugs frequently added to PD solutions in clinical practice have been shown to reduce the viability and to impair the function of mouse peritoneal cells. The cytotoxicity of PD solutions, directly related to the dextrose concentration, was more marked towards resident than elicited peritoneal cells. None of the drug additives, heparin and insulin amongst them, were cytotoxic when tested alone or combined with 4.25% PD solution, with the exception of phosphatidylcholine which markedly enhanced the cytotoxicity of the PD solution. While the function of mouse peritoneal macrophages as measured by their hydrogen peroxide production was largely unaffected by PD solutions and drug additives when tested separately, the combination of 4.25% PD solution with any of the drug additives resulted in complete abolition of macrophage respiratory burst. The results should caution against the indiscriminate addition of drugs to PD solutions in dialysis patients. PMID- 2243578 TI - Renal disease in a patient with hereditary complete deficiency of the fourth component of complement. AB - Hereditary complete deficiency of the fourth component of complement (C4) is an extremely rare disorder with 17 cases reported so far. Twelve of these patients suffered from a systemic-lupus-erythematosus-like illness. The patient we here describe presented with severe Henoch-Schonlein purpura (HSP) at the age of 17. Immunofluorescence of a kidney biopsy showed granular deposits of IgG, IgA, IgM, C3 and fibrinogen in the mesangium and segmentally along the basement membrane. Six years later, the patient developed hypertension and nephrotic syndrome. Renal function deteriorated rapidly. He was on hemodialysis for 12 months and then received a cadaveric kidney graft. After 2 years of uncomplicated course, microhematuria and proteinuria developed. Immunofluorescence of a transplant biopsy was virtually identical to the pattern in the patient's own kidneys. We thus conclude that the patient had recurrence of his primary disease in the graft. Three and a half years after transplantation hemodialysis had to be restarted. This unique case supports the current view that deficiency of classical pathway components predisposes to the development of immune complex diseases and that the complement system is activated via the alternate pathway in HSP. Furthermore, we assume that complete C4 deficiency was the major cause for the recurrence and unfavorable outcome of HSP in the graft. PMID- 2243579 TI - Sternoclavicular joint infection in hemodialysis patients. AB - Infection of the sternoclavicular joint due to Staphylococcus aureus occurred in 2 hemodialysis patients. Good results were achieved in both cases by applying appropriate antibiotic therapy. Sternoclavicular joint sepsis is rare. However, it is often associated with underlying conditions, and hemodialysis must be recalled as one of the possible predisposing factors. PMID- 2243580 TI - Chronic nephritis, sensorineural deafness, growth and developmental retardation, hyperkinesis, and cleft soft palate in a 5-year-old boy. A new combination? AB - A 5-year-old Japanese boy showed nephritis similar to, but distinct from, that in Alport syndrome. Nephrotic syndrome without hematuria was noticed at age 2, although renal biopsy at age 4 revealed widespread irregular thickening of the glomerular basement membrane with splitting of the lamina densa on electron microscopy, characteristic of nephritis in Alport syndrome. Sensorineural deafness was noticed at age 4 weeks by no auditory brain stem response, unusually early for Alport syndrome. Goodpasture antigen and amyloid P component were found in the glomerular basement membrane. Thus, the antigenicity of the glomerular basement membrane was different from that in male patients with X-linked Alport syndrome. In addition, growth and developmental retardation, hyperkinesis, and cleft soft palate were seen. These features are a hitherto undescribed combination. The family history was negative for any of the features of the boy. PMID- 2243581 TI - Different answer to recombinant human erythropoietin in anephric and non-anephric haemodialyzed patients. PMID- 2243582 TI - Increased activity of the autonomic nervous system and increased sensitivity to angiotensin II infusion after therapy with recombinant human erythropoietin. PMID- 2243583 TI - Hydrocephalus associated with malignant hypertension and renal failure. PMID- 2243584 TI - Reactivation of hepatitis B virus by corticosteroids in a case of idiopathic nephrotic syndrome. PMID- 2243585 TI - Weight reduction in massive obesity associated with focal segmental glomerulosclerosis: another evidence for hyperfiltration? PMID- 2243586 TI - Mechanism of hemodialysis-associated subclavian vein stenosis. PMID- 2243587 TI - Effects of visual deprivation on the postnatal development of the geniculocortical projection in kittens. AB - In kittens reared with either monocular, binocular or reverse suture, beginning before the physiological eyelid opening (around one week of age) and lasting until after one month, the cortical laminar distribution of geniculocortical afferents to area 17 was examined by using orthograde transport of wheat germ agglutinin conjugated with horseradish peroxidase, and compared with that in normal kittens. In normal kittens, at birth, the afferents were distributed most densely in layer I and, to a lesser extent, widely from the upper part of layer II to layers V or VI. After one month, the afferents were found mainly in and around layer IV and very sparsely in layer I. Neither binocular nor monocular suture affected this normal development. In contrast, when the present procedure of monocular suture had been followed by opening the sutured lid and suturing the other lid (reverse suture) for one week, the distribution was altered. The density of the afferents in layer I was increased while the labelled terminals in deeper layers were as segregated in and around layer IV as observed in normal kittens. Such increase in density of the afferents resulted only when the injected tracer covered the medial or intermediate part of the C complex of the lateral geniculate nucleus. To confirm these findings, geniculate neurons retrogradely labelled by horseradish peroxidase injections into layer 1 of area 17 were examined in normal and reverse-sutured kittens. In both kinds of kittens, the labelled neurons were dense in the C complex, and absent or sparse in the A laminae. But, the number was higher in reverse-sutured kittens. These results suggest an involvement of geniculocortical layer I projections in reorganization of neuronal circuits in the visual cortex. PMID- 2243589 TI - Ionic dependencies of tetrodotoxin-resistant action potentials in trigeminal root ganglion neurons. AB - Action potentials recorded in vitro from the perikarya of trigeminal root ganglion neurons (guinea-pig) were examined for their sensitivities to blockers of specific ion channels or to removal of certain ionic species in the bathing media. The majority (approximately 65%) of the 137 neurons exhibited action potentials following application of the Na(+)-channel blocker, tetrodotoxin. This group of neurons was selected for further investigation under conditions of extracellular K(+)-channel blockade with tetraethylammonium and 4-aminopyridine. Long-duration action potentials consisting of two distinct components could be evoked under such conditions. The fast component of the spike was abolished in Na(+)-deficient perfusion media and was sensitive to blockade by extracellular lidocaine or intracellular QX-222 applications. It is likely that the slow component was mediated mainly by Ca2+, but in Ca2(+)-deficient media. Mg2(+) influx may have contributed to the small voltage response. The amplitude and shape of the slow component was unaffected by applications of lidocaine or QX 222. Self-sustained repetitive firing was also observed in 11 neurons in the above conditions. This activity persisted even under conditions of severe deficiencies in extracellular [Ca2+] or [Na+]. Two distinct but overlapping K(+) conductances that were sensitive to blockade by internal Cs(+)-application and insensitive to applications of tetraethylammonium and 4-aminopyridine, appear to mediate the afterhyperpolarization of the long-duration spike. One portion of the afterhyperpolarization was 60-150 ms in duration and was unaffected by removal of Ca2+ from the extracellular media, while the other had a time-course lasting 150 250 ms and was abolished by removal of external Ca2+. In some neurons, these K(+) conductances were blocked by high doses of doxorubicin or cisplatin. The results show that at least two ion species (Na+ and Ca2+) contribute to the formation of the tetrodotoxin-resistant, long-duration action potential in trigeminal root ganglion neurons during selective K(+)-conductance blockade and also provide evidence for Mg2+ involvement in the generation of this voltage response. PMID- 2243590 TI - Effects of microdialysis on brain metabolism in normal and seizure states. AB - The effect of intracranial microdialysis on brain glucose metabolism in control and kainic acid-treated rats was assessed by semi-quantitative [14C]2 deoxyglucose autoradiography. A dialysis fiber loop was implanted into the piriform cortex or a horizontal Vita fiber into the hippocampus, and 24 h later, fibers were perfused with Krebs-Ringer bicarbonate solution before and after injection of kainic acid (16 mg/kg, i.p.) [14C]2-Deoxyglucose was injected i.p. 3 h after the injection of kainic acid. Rats injected with kainic acid were initially lethargic and then proceeded through behavioral phases of staring, "wet dog shakes", Straub tail, rearing, forepaw clonus, and, in some cases, tonic clonic convulsions. Three hours after kainic acid, the fiber presence in the piriform cortex enhanced kainic acid-induced metabolic activity in areas adjacent to the fiber assembly, whereas the fiber in hippocampus attenuated kainic acid induced metabolic activity in areas adjacent to the fiber assembly. The results indicate that intracranial microdialysis alters the already abnormal brain metabolism in a kainic acid-induced seizure state, but has no significant effect in the non-seizure control state. PMID- 2243588 TI - Dopamine high-affinity transport site topography in rat brain: major differences between dorsal and ventral striatum. AB - Investigations were conducted to determine the topography of the high-affinity dopamine uptake process within the rat striatum. [3H]Dopamine uptake into crude synaptosomes prepared from micropunch samples was found to be two- to three-fold higher in dorsal caudate-putamen relative to nucleus accumbens septi. In contrast, the concentrations of dopamine in the two regions were equivalent. The recognition site associated with high-affinity dopamine uptake was labeled using [3H]mazindol, and the binding of this ligand was also found to be two- to three fold higher in homogenates from dorsal caudate-putamen samples relative to nucleus accumbens septi. Regional differences in uptake of [3H]dopamine or binding of [3H]mazindol were shown to be due to variations in Vmax or Bmax, not to differences in apparent affinity. Autoradiography of [3H]mazindol binding in rat striatum revealed a decreasing density of the site along the dorsal-to ventral axis, with the highest binding occurring in the dorsolateral caudate putamen, lower binding in the ventral caudate-putamen, and lowest levels in the septal pole of the nucleus accumbens septi. Quantification showed that the extent of this gradient was two-fold. Further autoradiographic studies revealed less striatal heterogeneity in the pattern of binding of [3H]ketanserin, another radioligand associated with the striatal dopaminergic innervation but not linked to the dopamine uptake process of the plasma membrane. The findings suggest that the dopaminergic fibers of the ventral striatum, especially the medial nucleus accumbens septi, may be relatively lacking in their capacity for dopamine uptake following its release. This organization may result in regional differences in the time-course of of extraneuronal dopamine following transmitter release and may render the dopamine-containing terminals of the ventral striatum less susceptible to the degenerative influences of neurotoxins that are incorporated by the high-affinity dopamine uptake process. PMID- 2243591 TI - Distribution of glutamate decarboxylase-containing neurons in rabbit medulla oblongata with attention to intramedullary and spinal projections. AB - Functional studies in the rabbit suggest that GABA is an important inhibitory neurotransmitter in the control of cardiovascular, respiratory and neuroendocrine functions by the medulla oblongata. The present work was undertaken to provide a description of the distribution in the rabbit medulla of neurons containing glutamate decarboxylase, an enzyme present in GABA-synthesizing neurons. Combined retrograde axonal transport and immunohistochemical studies were carried out to determine intramedullary and spinal projections of immunopositive neurons located in regions particularly relevant to the interpretation of functional studies. Neurons containing glutamate decarboxylase, putatively GABA-containing neurons, were found in all nuclei of the rabbit medulla with the exception of somatic cranial nerve nuclei and the lateral reticular nucleus. The immunopositive cells were distributed throughout individual nuclei and their morphological appearance was similar to that of neighbouring immunonegative neurons in the nucleus. An exception was encountered in the dorsal motor nucleus of the vagus where the glutamate decarboxylase-containing neurons belong to a population of small neurons easily distinguished from the larger vagal preganglionic cells. Many immunopositive cells in the raphe nuclei, in the medial reticular formation and in the vestibular nuclei have axonal projections to the spinal cord and presumably represent sources of inhibitory bulbospinal control. Within the medulla there were glutamate decarboxylase-containing neurons in the nucleus tractus solitarius with projections to caudal but not to rostral regions of the ventrolateral medulla. These neurons could provide a GABAergic input to respiratory, cardiovascular and neuroendocrine neurons in the caudal ventrolateral medulla. Immunopositive cells projecting from the caudal to the rostral ventrolateral medulla could form part of the population of inhibitory vasomotor neurons known to be present in the caudal ventrolateral medulla. Some glutamate decarboxylase-containing neurons just medial to the nucleus ambiguous in the rostral medulla, in the region containing the Botzinger group, project to the caudal ventrolateral medulla and could therefore provide an inhibitory input to caudal respiratory cells. PMID- 2243592 TI - A pontine call site in the domestic cat: behavior and neural pathways. AB - Electrical stimulation of the brain of the domestic cat elicited vocalizations from a site in the ventrolateral pons in the region of the medial lemniscus. The evoked vocalizations were analysed by means of sound spectrographs and classified as meows, growls, hisses and meow-growls. The neural pathways associated with these call sites were traced by following the pattern of fiber degeneration resulting from lesions placed at these sites. A descending fiber pathway was traced to the magnocellular tegmental field, the facial nucleus and the retrofacial nucleus, while an ascending system terminated in the zona incerta, the red nucleus, contralateral oculomotor nucleus, the ventroposterior lateral nucleus of the thalamus and inferior colliculus. It is concluded from these findings and the nature of the behavior evoked that the ventrolateral pontine call site lies on common pathway for a majority of vocalizations in the cat. PMID- 2243593 TI - Regulation of the post-translational conjugation of amino acids to rat brain proteins. AB - Post-translational conjugation of arginine (but not other amino acids) to proteins has been reported to occur in a high speed supernatant fraction of rat brain homogenates from which molecules of less than 5000 mol. wt have been removed. In the present study we report that removal of molecules of less than 1000 mol. wt by dialysis, does not result in incorporation of arginine into protein in amounts significantly different than in the undialysed supernatant. The addition of molecules with molecular weights greater than 1000 and less than 5000 to the active fraction, inhibits the incorporation of arginine into proteins in a concentration dependent manner suggesting that the post-translational incorporation of arginine into brain is regulated by a molecule(s) of greater than 1000 and less than 5000 mol. wt. Incorporation of lysine into proteins did not occur following removal of molecules of less than 5000 mol. wt, but did occur in the void volume fraction of a Sephacryl S-200 column (molecular weight cut-off 125,000), suggesting that the incorporation of lysine into proteins is regulated by molecules retained by the S-200 column but greater than 5000 mol. wt. When experiments were repeated using the void volume of a Sephacryl S-300 column (molecular weight exclusion, approximately 200 k), leucine and proline were incorporated in amounts similar to arginine and lysine and serine, alanine, valine, phenylalanine and histidine were incorporated at lower but measurable levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243594 TI - Opioid antagonist (naltrexone) stimulation of cell proliferation in human and animal neuroblastoma and human fibrosarcoma cells in culture. AB - Endogenous opioids play a role in carcinogenic events by serving as inhibitory growth factors that alter cell proliferative events by interaction with opioid receptors. The present study addresses the question of whether endogenous opioid systems function tonically in tissue culture. Using S20Y neuroblastoma, a cell line that produces a growth-related opioid peptide (i.e.[Met5]enkephalin) and contains the zeta receptor known to be associated with growth, the effects of opioid receptor blockade by naltrexone, a potent opioid antagonist, was examined. Drug concentrations of 10(-4) to 10(-8) M naltrexone stimulated cell proliferation, with 32-86% more cells found in the naltrexone groups than control from 12 to 48 h after initiating drug exposure; drug concentrations of 10(-9) to 10(-13) M had no effect on growth. Evaluation of labeling and mitotic indices revealed that both DNA synthesis and mitosis were increased by naltrexone, as were the number of cells with process lengths greater than 40 microns. Naltrexone (10(-6) M) also stimulated the growth of N115 murine neuroblastoma, SK-N-MC human neuroblastoma, and HT-1080 human fibrosarcoma. These results indicate that endogenous opioids function in vitro to regulate growth by inhibitory mechanisms, and do so actively. This autocrine mechanism in tissue culture also occurs in other animal neuroblastoma cell lines, as well as for human neuroblastoma and fibrosarcoma cell lines. PMID- 2243595 TI - Modifications of the responses of barrel field neurons to vibrissal stimulation during theta in the awake and undrugged rat. AB - In partially restrained but awake and undrugged rats, excitatory unit responses of the somatic cortex barrel field to vibrissal stimulation, were recorded in two conditions: during spontaneous episodes of theta and in the absence of this rhythm. Two main variables were considered: a signal-to-noise ratio and an index of the "afferent inhibition". Both measures were extracted from peristimulus time histograms. "Theta effects" were characterized by an increase in signal-to-noise ratio and afferent inhibition. They were most important in neurons located in infragranular layers of the cortex; they went in the same direction but only approached significance in supragranular neurons; neurons of the granular layer were not affected. Spontaneous unit activity and latencies were not modified in any group. These data were obtained during a preliminary step of a sensory sensory conditioning procedure which in some cases modified the receptive field of the neurons. Theta effects were less marked in future "conditioned" than in future non-conditioned neurons but this was probably due to the fact that conditioned neurons had significantly higher signal-to-noise ratio and afferent inhibition. The origin of these "theta effects", hippocampal versus non hippocampal, and their functional significance, relation to selective attention, are discussed. PMID- 2243596 TI - Separate finger representations at the human second somatosensory cortex. AB - We recorded neuromagnetic responses of the second somatosensory cortex in healthy humans. Cutaneous electrical stimulation of fingers elicited a response around 100 ms, with a field pattern agreeing with activation of the second somatosensory cortex in the upper bank of the Sylvian fissure. In an oddball paradigm, with standards presented to the thumb and deviants (10%) to the middle finger, or vice versa, the second somatosensory cortex responses to deviants were almost three times as high in amplitude as those to standards. A similar amplitude enhancement was obtained when the deviants were presented in the absence of the intervening standards but with the same interstimulus interval. The results indicate that an accurate functional representation of different body areas is maintained at the human second somatosensory cortex. PMID- 2243597 TI - Biosynthesis and expression of ependymin homologous sequences in zebrafish brain. AB - Ependymins are unique, brain specific glycoproteins, which are major constituents of the cerebrospinal fluid. Originally, they were discovered in goldfish and are thought to be involved in synaptic plasticity. In the present study two transcripts were characterized in Brachydanio rerio originating from a single gene possibly by alternative splicing. These transcripts differ only in the length of their 3'-non-coding-regions and the encoded protein shares 90 and 88% homology with the two corresponding goldfish proteins, respectively. In situ hybridization revealed the expression of ependymins exclusively in the leptomeninx including its invaginations but not at all in the ependymal layer surrounding the ventricles. An initial developmental profile showed that ependymins first appear before hatching, i.e. between 48 and 72 h postfertilization. PMID- 2243598 TI - "On-line" measurement of acetylcholinesterase release from the substantia nigra of the freely-moving guinea-pig. AB - Acetylcholinesterase is released from dopaminergic cells within the substantia nigra. The functional significance of this phenomenon has been studied in the freely-moving animal by a novel system for measuring acetylcholinesterase release from the substantia nigra "on-line" and in vivo. In the unanaesthetized guinea pig the amount of acetylcholinesterase released was significantly greater than during anaesthesia, and release occurred in a more pulsatile manner. In addition, release of acetylcholinesterase could be evoked by either pharmacological or physiological manipulations, i.e. (1) a depolarizing concentration of potassium ions administered locally; (2) metamphetamine, administered systematically, which also resulted in increased locomotor activity; (3) drinking behaviour, elicited by presentation of a water bottle. Although all three treatments were accompanied by an increase in acetylcholinesterase release within the substantia nigra, potassium-evoked release did not cause any detectable change in behaviour. It is therefore suggested that release of the protein acetylcholinesterase within the substantia nigra is not necessarily a direct cause of locomotor activity: rather, it reflects diverse sensorimotor events. PMID- 2243599 TI - Afferents to the median raphe nucleus of the rat: retrograde cholera toxin and wheat germ conjugated horseradish peroxidase tracing, and selective D [3H]aspartate labelling of possible excitatory amino acid inputs. AB - Afferents to the median-paramedian raphe nuclear complex, which contains the B8 serotonergic cell group, were investigated in the rat with neuroanatomical and transmitter-selective retrograde labelling techniques. Injection of sensitive retrograde tracers, cholera toxin genoid or wheat germ agglutinin conjugated horseradish peroxidase into the median raphe resulted in labelling of neurons in a large number of brain regions. Projections from 26 of these regions are supported by available orthograde tracing data; the cingulate cortex, bed nucleus of stria terminalis, medial septum and diagonal band of Broca, ventral pallidum, medial and lateral preoptic areas, lateral hypothalamus, dorsomedial nucleus of hypothalamus, lateral habenula, interpeduncular nucleus, substantia nigra, central (periaqueductal) gray, and laterodorsal tegmental nucleus seem to represent major sources of afferents to the median-paramedian raphe complex. Retrogradely labelled cells were also observed in a number of regions for which anterograde tracing data are not available, including the perifornical hypothalamic nucleus, ventral premammillary nucleus, supramammillary and submammillothalamic nuclei and the B9 area. Possible excitatory amino acid afferents were identified with retrograde D-[3H]aspartate labelling. Microinjection of D-[3H]aspartate at a low concentration, 10(-4) M in 50 nl, resulted in retrograde labelling of a limited number of median raphe afferents. The most prominent labelling was observed in the lateral habenula and the interpeduncular nucleus, but retrogradely labelled cells were also noted in the medial and lateral preoptic areas, lateral and dorsal hypothalamus, ventral tegmental area, laterodorsal tegmental nucleus, medial parabrachial nucleus, and the pontine tegmentum. After injections of 10(-3) M D-[3H]aspartate selective labelling also appeared in more distant afferent regions, including cells in cingulate cortex, and in some regions located at shorter distances, such as the supramammillary nucleus. Injections of D-[3H]aspartate at high concentration, 10( 2) M, resulted in the appearance of weakly to moderately labelled cells in most afferent areas which were devoid of labelled cells after injections of lower concentrations, suggesting that this labelling may be non-specific. It was concluded that the median-paramedian raphe receives afferents from a large number of forebrain and hypothalamic regions, while relatively few brain stem regions project to this nuclear complex. The selectivity of retrograde labelling with D [3H]aspartate was found to be concentration dependent, and it is suggested that the connections showing high affinity for D-[3H]aspartate may use excitatory amino acids as transmitters. Excitatory amino acid inputs from lateral habenula and interpeduncular nucleus may play predominant roles in the control of ascending serotonergic and non-serotonergic projections originating in the median and paramedian raphe nuclei. PMID- 2243600 TI - Peripheral innervation of Opsanus tao (oyster toadfish). AB - Dual innervation, two morphologically distinct axons ending on the same endplate of white muscle, has been observed in some 'primitive' fish but not 'higher' teleosts. A representative of the order Bachtrachoidiformes, Opsanus tao, was examined using histological sectioning and silver impregnation to determine the innervation of its white muscle. The results demonstrate for the first time, dual innervation in the distributed pattern (innervation along the entire length of the white muscle fibers) in a 'higher' teleost. This indicates that Opsanus tao may represent a species of 'higher' teleosts that has either retained its ancestral mode of innervation (dual innervation) while exhibiting the derived distributed pattern or convergently evolved mode and pattern of innervation. PMID- 2243601 TI - Electron microscopic immunogold cytochemistry reveals chromogranin A confined to secretory granules of porcine Merkel cells. AB - By ultrastructural immunohistochemistry using the immunogold technique, immunoreactive (ir) Chromogranin A (CGA) was found to be confined to the secretory vesicles of porcine Merkel cells. CGA was present predominantly in the periphery of the electron-dense core and on the clear halo. These findings indicate that CGA is a regular constituent of Merkel cell secretory granules but probably not exclusively responsible for their electron opacity. PMID- 2243602 TI - Modification of olfactory bulb synaptic inhibition by early unilateral olfactory deprivation. AB - Early unilateral olfactory deprivation produces large structural and neurochemical changes in the olfactory bulb, the first central relay for olfactory information. The functioning of deprived bulbs was examined in the present report by using paired-pulse stimulation of the lateral olfactory tract. Paired-pulse stimulation reflects interactions between mitral/tufted cells and granule cells, as well as the modulatory effects of centrifugal and intra-bulbar association fibers. Paired-pulse stimulation produced inhibition of mitral/tufted cells in control animals at PN20-PN22. This inhibition was significantly enhanced in littermates deprived of olfactory input from PN1 to PN20-PN22. Suppression of mitral/tufted cell single-unit spontaneous activity following single-pulse stimulation of the lateral olfactory tract (LOT) was similarly enhanced in deprived bulbs. These results suggest that early olfactory deprivation significantly modifies subsequent olfactory system function. PMID- 2243603 TI - Basal dendrites are a regular feature of hippocampal granule cells in flying fox hippocampus. AB - The morphology of hippocampal granule cells was studied in two species of megachiropteran bats. In general the morphological appearance of megabat granule cells corresponded to that of other mammals. However, with respect to the regular presence of basal dendrites the majority of granule cells resembled their counterparts in primates, but differed from rodents and carnivores where basal dendrites are absent in adults. Due to the laminar segregation of hippocampal afferents basal dendrites are presumed to be functionally significant by receiving synaptic input from projections to the hilar region. PMID- 2243604 TI - Serotonin-synthesizing nerve fibers in rat and cat cerebral arteries and arterioles: immunohistochemistry of tryptophan-5-hydroxylase. AB - Nerve fibers synthesizing 5-hydroxytryptamine (5-HT or serotonin) were demonstrated in rat and cat cerebral blood vessels by immunohistochemical localization of the rate-limiting enzyme catalyzing the biosynthesis of 5-HT, namely tryptophan-5-hydroxylase (TPOH). TPOH-immunoreactive fibers were present in all parts of the circle of Willis with a somewhat less intense distribution in the vertebro-basilar segment. Single, small nerve fibers intermingled around the vessel wall were found in both species but clear TPOH-immunoreactive varicosities were observed predominantly in the rat. The most striking observation was the dense network of TPOH-positive fibers innervating some but not all small pial arteries, and, to a lesser extent, pial arterioles. These results provide the evidence that, at least in these species, the cerebrovascular bed is innervated by authentic serotonergic fibers which can synthesize their own 5-HT. PMID- 2243606 TI - A four-day period of bimodality auditory and visual experience is sufficient to permit normal emergence of the map of auditory space in the guinea pig superior colliculus. AB - Previous work has shown that if guinea pigs are deprived of simultaneous visual and auditory experience during a 4-day period 26-30 days after birth (DAB), this prevents the normal emergence of an auditory space map in the superior colliculus. The present work reports that if this 4-day period is the only developmental period in which the animals have simultaneous bimodality experience, the auditory space map appears at the normal time. Apart from this time-window animals were deprived of either visual experience (by dark-rearing) or of normal auditory experience (by rearing in an environment of omnidirectional masking noise). We conclude that the period 26-30 DAB is a crucial developmental period during which coincident auditory and visual experience is utilized in the initial formation of the collicular map of auditory space. PMID- 2243605 TI - Bis-oxonol experiment on plasma membrane potentials of bovine adrenal chromaffin cells: depolarizing stimuli and their possible interaction. AB - Changes of plasma membrane potential of isolated bovine adrenal chromaffin cells were monitored by fluorescent probe, bis-[1,3-diethyl thiobarbiturate]trimethineoxonol (bis-oxonol), which responds to depolarization, resulting in increase of its fluorescence. Excess K+, gramicidin D, veratridine and ouabain all increased bis-oxonol fluorescence. Cells challenged with acetylcholine (ACh) or gamma-aminobutyric acid (GABA) produced a steady-state increase of bis-oxonol fluorescence, reflecting that averaged depolarization occurred continuously. Both effects were dependent on concentration with similar range, and mediated via nicotinic ACh receptor and GABAA receptor, respectively. Application of GABA with ACh or veratridine not only simultaneously but also pretreatedly caused an additive increment of bis-oxonol fluorescence. These results suggest that chromaffin cells in vitro reveal an additively enhanced change of plasma membrane potential in response to the combination of depolarizing stimuli. PMID- 2243607 TI - Ascorbic acid: a useful reductant to avoid oxidation of catecholamines in electrophysiological experiments in vitro? AB - The actions of the reductant ascorbic acid on rat neocortical neurons in vitro was investigated by means of intracellular recordings. At a concentration (500 microM), which reduced the magnitude of dopamine degradation in oxygen-saturated saline solutions by about 50%, ascorbic acid reversibly depressed synaptic potentials and enhanced direct excitability of cortical neurons. The latter effect was not reversible within the observation period. Ascorbic acid did not alter membrane potential and input resistance of the neurons. On the basis of our results we conclude that ascorbic acid is not a useful reductant to avoid oxidation of catecholamines in oxygen-saturated solutions used in electrophysiological experiments in vitro. PMID- 2243608 TI - Depressant effect of raphe stimulation on inspiratory activity of the hypoglossal nerve: in vitro study in the newborn rat. AB - Respiratory activity was recorded from the hypoglossal nerve and cervical ventral roots of the superfused isolated brainstem and spinal cord of the newborn rat in order to investigate the effects of serotonin (5-HT). Three experimental procedures were used: (i) brainstem superfusion by exogenous 5-HT (previously reported), (ii) electrical stimulation of pontine midline structures, and (iii) pressure microejection of L-glutamate at the same sites. Each of the experimental procedure increased respiratory frequency and depressed the amplitude of the discharge of the hypoglossal nerve more than that of the cervical roots. These results indicate that 5-HT acts centrally to modulate the activity of the respiratory generator and inhibits the hypoglossal activity. A possible involvement of 5-HT mediated inhibition in obstructive apnea is discussed. PMID- 2243609 TI - Morphological and electrophysiological properties of C-cells in bullfrog dorsal root ganglia. AB - Dissociated bullfrog dorsal root ganglion cells were voltage-clamped in the whole cell configuration. Small spheroidal C-cells had a mean diameter of 14-30 microns and shared about 10% of the total population of the cells. The C-cells were characterized by a prominent calcium-activated potassium current underlying a hyperpolarization following the action potential. In contrast, a hyperpolarization-activated cationic inward rectifier was missing in all C-cells tested. These properties were completely different from those which have been observed for large spheroidal A-cells. PMID- 2243610 TI - Diurnal rhythms of immunoreactive melatonin in the aqueous humor and serum of male pigmented rabbits. AB - Using specific radioimmunoassays, melatonin was quantified in the aqueous humor and serum of male pigmented rabbits adapted to 12L:12D with lights on at 06.00 h. Melatonin concentrations in the aqueous humor at 08.00 and 16.00 h were similar (mean: 5.23 pg/ml) and significantly lower than those at 22.00 and 01.00 h (mean: 22.06 pg/ml). A parallel rhythm was also demonstrated in the serum with higher melatonin concentrations (daytime mean: 75.26 pg/ml; nighttime mean: 168.94 pg/ml). We propose that the aqueous melatonin rhythm is associated with the rhythmic change in aqueous flow. PMID- 2243612 TI - Histamine H1-receptor-like binding sites in the locust nervous tissue. AB - The histamine H1-receptor-like binding sites in the nervous tissue of the locust Locusta migratoria were investigated with a conventional radio-receptor assay using [3H]mianserin as the radio ligand. Binding of [3H]mianserin to the binding site is sensitive to proteases and heat treatment. It shows the characteristics of ligand-receptor interactions. The single binding site has high affinity for mianserin (KD = 7.05 nM) and is present in high concentrations (Bmax = 1.53 pmol/mg) in the whole nervous tissue. All tested antihistamines have a high affinity for the binding site, which suggests that it represents an insect histamine receptor. Nevertheless, it shows its peculiarities distinguishing it from vertebrate histamine H1-receptors. PMID- 2243611 TI - Protection from cerebral ischemic injury in gerbils with the spin trap agent N tert-butyl-alpha-phenylnitrone (PBN). AB - N-Tert-butyl-alpha-phenylnitrone (PBN), a spin trap agent, reduced ischemic hippocampal damage and the associated locomotor hyperactivity in Mongolian gerbils. Cerebral ischemia was induced in unanesthetized gerbils by a bilateral 5 min occlusion of the carotid arteries. PBN (100 mg/kg, i.p.) administered 30 min prior to carotid occlusion, prevented the increase in locomotor activity observed in saline-injected ischemic animals and significantly reduced damage to the hippocampal CAI pyramidal cell layer observed 5 days post-ischemia. These findings support the hypothesis of an involvement of reactive free radicals as a significant cause of ischemia-reperfusion-induced cerebral injury and suggest that PBN may be a useful agent for the prevention of cerebral ischemic damage. PMID- 2243614 TI - Muscarinic receptors mediate direct inhibition of GABA release from rat striatal nerve terminals. AB - The effects of acetylcholine (ACh) on the depolarization-evoked release of [3H]gamma-aminobutyric acid ([3H]GABA) have been investigated using synaptosomes prepared from rat corpus striatum and depolarized by superfusion with 9 mM KCl. Acetylcholine inhibited the [3H]GABA overflow in a concentration-dependent manner. The maximal effect was about 50%. The IC50 value (concentration producing half-maximal effect) amounted to 1 microM, in the absence of acetylcholinesterase inhibitors. The effect of ACh on the K(+)-evoked [3H]GABA release was counteracted by the muscarinic receptor antagonist atropine, but not by the nicotinic receptor antagonist mecamylamine or by the selective M1 antagonist pirenzepine. The data show that muscarinic receptors with low affinity for pirenzepine are localized on GABAergic nerve endings in rat corpus striatum where they may directly inhibit the release of GABA. PMID- 2243613 TI - Neural influence on the action of insulin in the adrenomedullary catecholamine content in the pigeon. AB - Insulin-induced (4 IU/100 g b.wt.) changes of adrenomedullary catecholamines (CA) were investigated in unilaterally splanchnic denervated pigeons 0.5, 4, 12, 24, 72, 144 and 216 h after injection. Insulin caused depletion of more norepinephrine (NE) from the denervated glands 0.5 h after treatment. This indicates that the splanchnic nerve prevents early phase of insulin-induced depletion of NE. Accelerated resynthesis of NE exceeding the control value was more in the innervated glands 24 h after administration. Insulin brought about augmented synthesis of epinephrine (E) surpassing the control value in the innervated glands 72 h after treatment. The findings point out that the splanchnic nerve stimulates resynthesis of NE and synthesis of E induced by insulin. PMID- 2243615 TI - The effect of acetylcholinesterase inhibition on the release of acetylcholine from the striatum in vivo: interaction with autoreceptor responses. AB - The release of acetylcholine from the rat striatum is under inhibitory control of muscarinic autoreceptors. Since in vivo release studies are generally performed in the presence of an acetylcholinesterase inhibitor, modifications of responses to muscarinic receptor agonists and antagonists may be expected. In this study we show that the addition of 0.1 microM neostigmine bromide to the perfusion Ringer in a dialysis experiment attenuates the responses obtained by infusion of 100 microM oxotremorine and potentiates the effect of infusion of 1 microM atropine. Furthermore it is shown that under physiological conditions the muscarinic autoreceptors are not fully occupied, since infusion of 1 microM atropine did not affect the release of acetylcholine when no acetylcholinesterase inhibitor was added to the perfusion Ringer. PMID- 2243616 TI - Age-related changes in the uptake of calcium channel blockers by brain capillary endothelial cells and synaptosomal fractions. AB - The effects of aging on the uptake of calcium channel blockers through brain capillaries to brain parenchyma were investigated. Two different piperazine derivatives, flunarizine and 1-[bis(fluorophenyl)-methyl]-4-(2,3,4 trimethoxybenzyl)piperazine (abbreviated as KB-2796), were orally administered to young and aged rats. The concentrations of the blockers in plasma, endothelial cells of the brain capillaries and synaptosomal fractions of the three brain regions were determined by high-performance liquid chromatography. Flunarizine was more incorporated into brain tissues than KB-2796 in both young and aged rats. The uptake efficiency of KB-2796 from the circulation to the brain decreased more remarkably than that of flunarizine in aged rats. The partition coefficients between n-octanol and water indicated that KB-2796 was less hydrophobic than flunarizine. These results suggest that the uptake of the chemicals seems to be influenced by their hydrophobicity and the age of animals given. PMID- 2243617 TI - Inhibition of human brain aromatic L-amino acid decarboxylase by cooked food derived 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and other heterocyclic amines. AB - A carcinogenic, food-derived heterocyclic amine, 3-amino-1-methyl-5H-pyrido[4,3 b]indole (Trp-P-2), was found to inhibit aromatic L-amino acid decarboxylase isolated from human brainstem. Trp-P-2 inhibited the enzyme activity toward L DOPA more markedly than that toward 5-hydroxytryptophan. The inhibition was competitive to a cofactor of the enzyme, pyridoxal-5-phosphate, and the Ki value of Trp-P-2 was 163 microM. The enzyme activity could be fully recovered after removal of Trp-P-2 by gel filtration, which indicates that the inhibition was reversible. Among a series of heterocyclic amines examined for their effects on the activity toward L-DOPA, Trp-P-2 was the most potent inhibitor, followed by 2 amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, then Trp-P-1. Another heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole also inhibited the enzyme. The inhibition of the decarboxylase activity by these heterocyclic amines may affect the catecholamine metabolism in human brain. PMID- 2243620 TI - Infectious diseases. Salmonella: what risk? PMID- 2243618 TI - Non-invasive brain stimulation reveals reorganized cortical outputs in amputees. AB - EMG responses to non-invasive electromagnetic brain stimulation (EMS) were recorded from arm muscles of congenital amputees. Responses were obtained with lower thresholds on the amputated than on the intact side and were evoked from a larger cortical area. Contracting muscles showed increased responses to EMS; the increase was more pronounced on the amputated side. Similar findings were obtained in one traumatic amputee who suffered an early amputation, but not in another patient with a late amputation. We conclude that in congenital amputees there is substantial reorganisation of the corticospinal system and that this may also occur in early traumatic cases. PMID- 2243619 TI - Cryptic Met-enkephalin in adrenal and portal vein during splanchnic artery occlusion shock in cats. AB - Adrenal vein (AD), portal vein (PV), and femoral artery (FA) plasma levels of immunoreactive (IR) Met-enkephalin pentapeptide (ME) and extended ME-IR forms, obtained after sequential incubation of plasma with trypsin and carboxypeptidase B, were examined in 4 cats during splanchnic artery occlusion shock at baseline (S1), during early shock (S2), late shock (S3), and after naloxone (1 mg/kg, i.v.) administration (S4). Early shock (S2) led to a significant increase in levels of extended and fully processed Met-enkephalin IR at all 3 collection sites (AD, PV, FA) without a change in proportional levels of extended Met enkephalin IR to the pentapeptide IR (ME). Naloxone administration during late shock (S4), however, resulted in a disproportionate increase (150-fold from baseline) in adrenal vein plasma levels of extended Met-enkephalin IR forms, as compared to ME IR (23-fold). In contrast, no changes in plasma levels occurred in PV and FA. PMID- 2243621 TI - Infectious diseases. Aspects of isolation care. PMID- 2243622 TI - Infectious diseases. Moving an infectious patient by air. PMID- 2243623 TI - Infectious diseases. The role of the specialist health visitor. PMID- 2243624 TI - The importance of fitness. PMID- 2243627 TI - It's not all doom and gloom for merged schools of nursing. PMID- 2243625 TI - Courses in health promotion. PMID- 2243626 TI - The Mersey beat: alive and well. PMID- 2243628 TI - Setting standards for primary nursing. PMID- 2243630 TI - The invisible nurse. PMID- 2243631 TI - Infectious diseases. Principles of microbiology. PMID- 2243629 TI - Managers under threat. PMID- 2243632 TI - 12th Taniguchi international symposium on visual science. Katata, Japan, November 27-December 1, 1989. Proceedings. PMID- 2243633 TI - The light-suppressible K+ conductance and evaluation of internal messenger candidates in the molluscan extraocular photoreceptor. AB - A photoreceptor potential produced by a decrease in membrane conductance was not thought to occur in any invertebrate photoreceptors. However, we have found that the molluscan extraocular photoreceptor, A-P-1 responds to light with a depolarizing receptor potential due to a decrease in K+ conductance, so that the photoresponse associated with a decrease in membrane conductance is not unique to the vertebrate photoreceptor. The properties that the light-suppressible K+ conductance is time- and voltage-dependent are explained by comparison with those of the single channel conductance obtained in patch-clamp of both vertebrate and invertebrate photoreceptors. The noise analysis of the light-induced current suggest that this macroscopic light-suppressible conductance consists of channels. It is concluded that the light-suppressible K+ conductance is mediated by hydrolysis of cGMP which reduces internal cGMP, in agreement with the cGMP hypothesis of vertebrate phototransduction and that the hydrolysis may be modified by IP3. PMID- 2243634 TI - Effects of ions and drugs on the responses of sensory axon terminals of decapsulated frog muscle spindles. PMID- 2243635 TI - Calcium inhibition of ATP-dependent inactivation of rod disk phosphodiesterase in isolated rods and membrane suspensions. PMID- 2243636 TI - Forward and reverse transduction in the mammalian cochlea. PMID- 2243637 TI - Mechano-electrical transduction and muscarinic cholinergic responses in the chick hair cell. PMID- 2243638 TI - Results of treatment of cancer of the cervix in Wellington 1980-4. AB - A review was undertaken of all 115 women with invasive carcinoma of the cervix referred for treatment to the Wellington regional centre during the period 1980 4. In comparison with the previous five year period, there were 31 (37%) more patients, and a higher proportion of patients had stage I and II disease. The incidence of disease was significantly greater in Maori compared with nonMaori. Treatment was by various combinations of surgery and radiation according to agreed protocols. The actuarial survival at five years was 73% for the whole group, 89% for 64 stage I patients, 65% for 28 stage II patients and 45% for 19 stage III patients. The actuarial risk of a major treatment complication within the first five years was 8.8%. These results confirm that regional centres in New Zealand employing a multidisciplinary approach to patient assessment and treatment can achieve high cure rates with an acceptable incidence of treatment complications. However, prevention of the disease by effective cervical screening programmes should remain an objective of health services in New Zealand. PMID- 2243639 TI - Domestic unintentional injuries presenting to the accident and emergency departments in the Wellington region. AB - A prospective descriptive study of domestic unintentional injuries attending accident and emergency (A & E) departments in the Wellington region is presented. In a three month period there were 2207 such attendances. There was no difference in the proportion of males and females seen. A disproportionate number of the very young (under five years of age) and the elderly (65 years and over) attended A & E departments for these injuries. Approximately one-quarter of the attendances were for cuts or lacerations (26.6%) and one-fifth were for fractures (18.0%). Crude estimates of distance indicate that, on average, people travel greater distances for fractures than for other injuries. General practitioners referred one-tenth (10.6%) of all the attendances. Outcomes from the A & E attendances were: 70.4% were discharged, 7.7% were admitted to hospital, 14.6% were referred to outpatient clinics, and 7.2% were referred back to their general practitioners. There were no deaths in A & E departments. PMID- 2243640 TI - Passive smoking in childhood. PMID- 2243641 TI - A questionnaire survey of symptoms in a hypertension clinic. AB - OBJECTIVE: to assess symptoms of patients on antihypertensive therapy. SETTING: hospital hypertension clinic. DESIGN: self administered questionnaire (sent and returned by mail) listing 23 symptoms; four grades of response (none, mild or seldom, moderate or sometimes, severe or frequent); special scale for nocturia and appetite. PATIENTS: 302 patients completed the questionnaire (87% of those to whom it was sent); 109 of these patients completed it a second time, after an interval of four months, so that repeatability could be assessed. REPEATABILITY: scores were high, ranging from 0.92 to 0.99, for all symptoms except flushing (all grades 0.91), nausea (all grades 0.90) and sleepiness (severe, 0.82) (method of Bulpitt et al). RESULTS: overall prevalence of symptoms was high, but most were mild or infrequent. Women had significantly greater prevalence of oedema, flushing and insomnia than men and tended to assess their symptoms more often as severe or frequent. Nocturia was the only symptom more common in those above median age (62 yr) than in those below. Lack of energy was the only symptom more prevalent in the treated than in the untreated. No difference in prevalence of symptoms was detected between those taking or not taking a specific type of drug (beta blocker, diuretic, ACE inhibitor, calcium antagonist). CONCLUSION: in patients whose antihypertensive therapy has been carefully adjusted to try to avoid symptomatic side effects, the burden of such side effects appears to be very small. PMID- 2243642 TI - Important features associated with acute anterior cruciate ligament injury. AB - The mechanism of injury and the signs and symptoms associated with initial injury to the anterior cruciate ligament were investigated in 23 subjects. The subjects had injured only their anterior cruciate ligament with no other clinically definable laxity to other major ligamentous structures. The results showed that 70% of subjects had injured their anterior cruciate ligament at footstrike during noncontact situations. In 53% of these subjects the mechanism of injury was internal rotation of the tibia with the knee in slight flexion. A shifting sensation occurring between the tibia and femur was noted by 61% of subjects, while 30% recalled a crack or popping sound at the time of injury. Only 17% of subjects could continue in sports activity immediately following the injury, all with difficulty. PMID- 2243643 TI - The helpless dying. PMID- 2243644 TI - Importance of advanced surgical training. PMID- 2243645 TI - The state and general practice. PMID- 2243646 TI - Hyperbaric oxygen chamber at Devonport. PMID- 2243647 TI - AIDS awareness. PMID- 2243649 TI - Local anaesthetic allergic reactions. PMID- 2243648 TI - Tobacco and biotoxins. PMID- 2243650 TI - Targeting early detection of malignant melanoma of the skin. AB - Incidence and mortality rates, and clinical stage at diagnosis were analysed for malignant melanoma of the skin in recent years to assist in identifying high risk groups. Over 12 years to 1985-6 age standardised melanoma mortality rates in the nonMaori population increased 90% among men and 16% among women. In most age groups the male death rate was twice the female rate. Almost half the deaths from melanoma in 1983-6 were in men aged 45 or older. Age standardised incidence rates, for each sex, continued to increase to 1983-4. Among older age groups melanomas were less likely to be localised at diagnosis. This fall in localisation occurred at much younger ages (about 40) among men than among women. Middle aged men and older men and women are important target groups for education about the early detection of melanoma. PMID- 2243651 TI - Reactive arthritis, infection and antigens. PMID- 2243652 TI - The Nelson general practice prescribing project. Part I: A pilot audit of the regional prescribing profile. AB - The Nelson general practice prescribing project has been set up to develop a model for cost effective prescribing in general practice. A pilot audit of regional prescribing patterns and trends for February 1989 was conducted to test data acquisition and presentation for the project, based on 12,690 scripts. There was marked variation in medicines choice, cost and number of scripts between general practitioners. The cost of prescriptions ranged from $2.20 to $127.70, median $10.77. Cardiovascular medicines were most frequently prescribed and most costly. Extemporaneous prescribing accounted for 20% of the February inventory and was highly individually variable. Benzodiazepine prescribing was not in line with current guidelines and was high, mean 6.7% of all prescribing, indicating an urgent need for unbiased drug information. Audited prescription data allows definitions of educational and pricing strategies. PMID- 2243653 TI - The Nelson general practice prescribing project. Part II: Prescribing reports for self audit. AB - A special format is described for individualised feedback of audited prescribing information to practitioners. The format has been developed for general practitioners participating in the Nelson prescribing project (part I), and has been successfully trialed in conjunction with a preferred medicines list, specifically compiled for the Nelson region. The unbiased, reliable information is seen as a practical means of regular prescribing update and modification of medicine choice, as yet unexploited. PMID- 2243655 TI - Changing patterns of referral to an eating disorders clinic. AB - A decline in overall referrals was noted at the eating disorders clinic, Manawaroa centre for psychological medicine in 1987. At the same time a proportional increase in referrals for bulimia was observed. To gather more information on these apparent changes, data on the clinic's referral pattern were collected and general practitioners in the area health board district were surveyed. The results suggested a relatively stable referral rate from 1983-9, with an average of 31 referrals per year. However, there appears to have been a decrease in anorexia nervosa, from over 50% of referrals in 1983 to approximately 5% of referrals in 1988-9, and a corresponding rise in bulimia from 8% in 1983 to 49% in 1988 and 35% in 1989. Responses were received from 61 general practitioners, 78% of those surveyed. Most general practitioners indicated that they perceived a need for an eating disorders clinic, but only 40% had referred to the clinic. The main reasons given for not referring were: no appropriate patients (33%), the general practitioner was unaware of the clinic (29%), and the patient was being maintained by the general practitioner (25%). PMID- 2243654 TI - Random urine albumin:creatinine ratio measurements as a screening test for diabetic microalbuminuria--a five year follow up. AB - Serial random urine samples have been collected from 167 insulin treated diabetic patients attending the Waikato diabetes clinic from 1984 to 1989 and albumin/creatinine ratios measured as a screening test for diabetic microalbuminuria. The group ranged in age from 12 to 50 years and comprised 79 males and 88 females. Where the initial test was normal (less than 2.5), as found in 117 patients, 86.7% of all tests over the five year period (1032) remained normal. Of 50 patients with an initial elevated value, 39% of a total of 575 values taken over the five year period were subsequently normal. CONCLUSION: a random urine albumin measurement taken at yearly intervals is an adequate screening programme for patients with an initial normal value. PMID- 2243656 TI - Fetal and placental weight as predictors of adult hypertension. PMID- 2243657 TI - Overwhelming influenza B infection in an infant. PMID- 2243658 TI - Fenoterol prescribing and asthma severity. PMID- 2243659 TI - AST/ALT ratios. PMID- 2243660 TI - Double gloving during surgery: a technical tip. PMID- 2243661 TI - Hot water cylinders. PMID- 2243663 TI - Serum levels of tumor-associated glycoprotein (TAG-72) in digestive cancers. AB - Serum levels of tumor-associated glycoprotein (TAG-72) were measured using a two step sandwich radioimmunoassay kit in 281 patients with digestive cancers and 135 patients with benign digestive diseases. The positive rates of TAG-72 with the cut-off values of 2.2 and 4.0 U/ml were high in pancreatobiliary (56%, 38%), gastric (49%, 37%) and colorectal (62%, 29%) cancers, while the false-positive rate in benign diseases was 11%, 0.7% respectively. Very high levels were found in patients with advanced cancer. TAG-72 was positive in 17 (greater than 2.2 U/ml) and 7 (greater than 4.0 U/ml) out of 60 CEA-negative patients, and in 7 (greater than 2.2 U/ml) and 3 (greater than 4.0 U/ml) out of 17 CA19-9-negative patients. TAG-72 might be a useful serum marker for digestive cancers, especially gastric and colorectal cancers. PMID- 2243662 TI - Use of a fully implantable drug delivery system in the treatment of acute leukemias and disseminated lymphomas. AB - In an open study, 42 venous Port-A-Cath systems (PAC) were implanted in 40 patients with AML (12), ALL/AUL (11), NHL with bone marrow infiltration (8), Hodgkin's lymphoma (3), solid tumors (5) and severe aplastic anemia (1). Mean duration of system use was 212 days. The cumulated duration of use of all systems was 8.883 days. 1,627 blood samples were taken from the PAC. Blood sampling was possible on 8,696 of 8,883 days of cumulated access (98%). A total of 522 blood transfusions were administrated. Fifty-two episodes of neutropenia (granulocyte counts less than 0.5 x 10(9)/l) with a mean duration of 17 days were observed in the group of the 23 patients with acute leukemias. A total of 25 complications were registered. The incidence was 2.8/1,000 days of access. Twelve complications were regarded as severe. Venous thrombosis was observed in 3 cases. In addition, there were 2 disruptions of the catheter, 1 disconnection, 1 looping and 4 local infections. The rate of systemic infection could not be accurately estimated because the catheter was always left in place and antibiotic treatment was started immediately in case of fever with or without bacteriemia. The overall rate of catheter-related complications in patients with acute leukemia was not higher than in patients with solid tumors. PMID- 2243664 TI - Medical history, diet and pancreatic cancer. AB - The relation between various aspects of medical history, selected indicator foods and the risk of pancreatic cancer was analyzed in a hospital-based case-control study conducted in Northern Italy on 247 patients with cancer of the pancreas, and 1,089 controls in hospitals for acute, nonneoplastic or digestive conditions. There was a significant association with history of pancreatitis (relative risk, RR 3.2, 95% confidence interval = 1.3-7.9), which was however reduced when the condition was first diagnosed at least 5 years previously. The point estimates were slightly, but not significantly, above unity for diabetes (RR = 1.5), gastrectomy (RR = 1.1) and cholelithiasis (RR = 1.3), and no association was found with liver disease or drug allergy. In relation to diet, there was some tendency for the risk to decrease with more frequent fruit consumption, but the results were largely inconsistent in relation to various indicators of meat, animal protein or fat intake. Although no important associations were found in this study with various aspects of medical history or diet indicators and pancreatic cancer risk, on account of the size of the dataset and the statistical power, this study contributes usefully to the debate on a common cancer whose causes are still largely undefined. PMID- 2243665 TI - Multiple malignant neoplasms in patients with nasopharyngeal carcinoma. AB - The records of 759 patients with nasopharyngeal carcinoma were reviewed. Fifteen of them also suffered from another malignant neoplasm. All patients had histological confirmation of the nasopharyngeal carcinoma and the other malignant neoplasm. There was no predilection for the second malignant neoplasms to arise from the bronchus. Although the observed number of second malignant neoplasms was not significantly different from the expected number (p greater than 0.05) computed by the patient-month approach, in 1 patient the second malignant neoplasm may be causally related to the previous treatment of nasopharyngeal carcinoma by radiotherapy. PMID- 2243666 TI - Induction of tumor necrosis factor in human peripheral-blood mononuclear cells by proteolytic enzymes. AB - We could demonstrate that polyenzyme preparations as well as bromelain and papain stimulate the production of tumor necrosis factor-alpha in human peripheral-blood mononuclear cell cultures in a time-dependent manner. We give evidence that immunomodulation and especially the release of cytokines may contribute to the therapeutic effect of these preparations. PMID- 2243667 TI - Flow-cytometric analysis of colorectal cancer with hepatic metastases and its relationship to metastatic characteristics and prognosis. AB - Studying the DNA ploidy patterns of 52 primary tumors, diploid tumors accounted for 48.1% and aneuploid tumors for 51.9%. Out of 31 patients with liver metastases, 35.5% had diploid tumors and 64.5%, aneuploid tumors. Heterogeneity (difference in DNA ploidy pattern between the primary lesion and liver metastases) was found in 20% of the patients examined. In 28 of the patients, the liver metastases were unresectable, and their prognoses were such that the 1- and 2-year survival rates from the diploid tumors were 42.9 and 14.3%, respectively, while 1-year survivors from aneuploid tumors died within 2 years. In resected cases of hepatic metastases, the DNA ploidy pattern of the metastatic lesions did not correlate with the metastasis period, extent of spread or number of lesions. The recurrence rate of aneuploid tumors in the residual livers was 50%, which was slightly higher than the rate of 36.4% for diploid tumors. The prognoses in patients with diploid tumors were significantly better than those in patients with aneuploid tumors: 5-year survival was 71.1% in diploid tumor patients, compared with 21% in aneuploid tumor patients. PMID- 2243668 TI - Generation and characterization of a low-degree drug-resistant human tumor cell line. AB - A 2780 human ovarian cancer cells, obtained from an untreated patient, have been exposed to a relatively low, clinically maintainable dose (10 nmol/l) of the anthracycline doxorubicin (DX) to derive a low-degree (5-fold) drug-resistant subline (A2780-DX1). Compared to parental cells, these DX-resistant cells have increased size (+60% of cell volume) and contain a greater number of cytoplasmic vacuoles as determined by electron microscopy. When exposed to several other antiproliferative drugs, A2780-DX1 cells were highly cross-resistant (greater than 10-fold) to epirubicin, mafosfamide and cisplatin and slightly cross resistant (2- to 3-fold) to navelbine and bleomycin, while they retained the original sensitivity to vinblastine, Ara-C and fluorouracil. Gel electrophoresis of cytoplasmic membrane proteins showed differences between the pattern of parental A2780 sensitive and A2780-DX1 cells as far as low-molecular-weight proteins (less than 45 kD) are concerned, while no clear overexpression of P glycoprotein (P-170) could be detected. Membrane modifications yielding a decrease of both DX uptake and retention, increased content of intracellular glutathione (+32%) and reduced DNA double-strand breaks seem to be involved in the resulting multidrug-resistant phenotype of A2780-DX1 cells. PMID- 2243670 TI - Update on stromal puncture technique. PMID- 2243669 TI - Effect of alterations in permeability by nonionic surfactants on adriamycin cytotoxicity in murine tumor models in vitro. AB - Differential effects of adriamycin cytotoxicity and its cellular uptake were assessed in murine tumor models utilising adriamycin alone and in combination with nontoxic concentrations of nonionic polyoxyethylated lauryl ether surfactants Brij 30 and Brij 35. Parental P388 murine leukemia cell line sensitive to adriamycin, subline of P388 murine leukemia resistant to adriamycin, sarcoma-180 and Ehrlich ascites tumor were employed in this study. The results indicate an enhanced DNA biosynthesis inhibition by adriamycin when used in combination with Brij 30 or Brij 35 in all the murine tumor models. The increase in adriamycin cytotoxicity was due to an increased accumulation of adriamycin observed in the tumor models used. The present investigation demonstrates the necessity of utilising surface-active drug-response modulators to enhance the cytotoxicity of anticancer drugs and circumvent drug resistance. PMID- 2243671 TI - Efficacy of adding dipivefrin to a beta-blocker. PMID- 2243672 TI - Effectiveness of hyperbaric oxygen in treating radiation injury to the optic nerves and chiasm. PMID- 2243673 TI - Implications of decision analysis for ophthalmic practice. PMID- 2243674 TI - Prophylaxis of aphakic cystoid macular edema without corticosteroids. A paired comparison, placebo-controlled double-masked study. AB - Prior investigations have reported that topical nonsteroidal anti-inflammatory drug (NSAID) therapy prevents the development of postoperative angiographic signs of angiographic cystoid macular edema (CME). However, these studies include concurrent use of corticosteroids. The current study reports therapeutic efficacy for ketorolac ophthalmic solution (an NSAID) in the prophylaxis of angiographic aphakic CME (ACME) after cataract surgery without concurrent corticosteroids for the first time. Fifty patients with bilateral cataracts were enrolled in this placebo-controlled, paired-comparison, double-masked study. Eleven patients had evidence of angiographic ACME on postoperative day 40. Two of these patients demonstrated bilateral ACME, one patient had ACME in the NSAID-treated eye, and eight patients demonstrated ACME in the placebo-treated eye. This is a statistically significant difference favoring drug treatment. The signs of anterior ocular inflammation were greater in the eyes with ACME. This study suggests prophylactic treatment of ACME may be possible without the risks of concurrent corticosteroid toxicity. In addition, a higher incidence of ACME in black patients (22%) is observed in this study than has been recognized previously. PMID- 2243675 TI - Rapid determination of intraocular lens tilt and decentration through the undilated pupil. AB - The apparent optical axis of an implanted intraocular lens (IOL) can be located by alignment of the examiner's hand light with the third and fourth Purkinje images from the front and back surfaces of the IOL. Tilt of the IOL can be estimated (or measured with an arc perimeter) by the angle between the apparent optical axis and the patient's line of sight (actual tilt approximately 0.85 x apparent tilt). Decentration of the IOL is easily detected, equal to the distance of the IOL optical axis from the center of the pupil. This simple technique can be used through the natural pupil with posterior chamber IOLs, providing the optical axis of the malpositioned IOL still passes through the pupil. PMID- 2243676 TI - Sports-related ocular trauma. AB - A prospective evaluation of all patients presenting with a sports-related ocular injury during a 1-year (4-season) period was conducted. Of the 202 patients evaluated, 28 (13.8%) required hospitalization and 11 (5.6%) required intraocular surgery. Twenty-six patients (12.8%) sustained permanent ocular sequelae including seven (3.5%) who suffered visual loss. Basketball accounted for 28.7%, baseball/softball 19.8%, and racquetball 11.4% of all injuries. At the time of injury, 5.1% of patients had worn protective eye wear, whereas on follow-up only 31% had used eye protection. These results indicate that sports trauma remains a significant cause of ocular morbidity. PMID- 2243677 TI - Ki-67 immunostaining in uveal melanoma. The effect of pre-enucleation radiotherapy. AB - The reactivity of 33 choroidal and ciliary body melanomas with monoclonal antibody Ki-67, which recognizes a proliferation associated nuclear antigen, has been assessed and compared with clinicopathologic parameters. In 23 cases, 8 Gy irradiation was given 2 days before enucleation. Nonirradiated melanomas had a significantly higher proliferation rate as defined by staining with monoclonal antibody Ki-67 as compared with irradiated tumors (P = 0.007). Similarly, a strong relationship was found between pre-enucleation irradiation and low mitotic activity (P = 0.001). There was no significant correlation between the presence of Ki-67-positive nuclei and histologic classification, largest tumor diameter, localization of the tumor, age, sex, scleral invasion, pigmentation, and lymphocytic infiltration. The relevance of Ki-67 immunohistochemistry for the assessment of the life prognosis of patients with uveal melanoma has to be studied prospectively. PMID- 2243678 TI - Ocular syphilis. AB - The ability of syphilis to mimic different ocular disorders can lead to misdiagnosis and delay in appropriate antimicrobial therapy. The authors describe their experience over the past 5 years with the ocular manifestations of syphilis in 25 patients who comprised 2.45% of 1020 new patients. Uveitis was the most common ocular manifestation seen. All patients had positive results from FTA-ABS tests, whereas only 68% had reactive serum VDRLs. Two of five patients tested for human immunodeficiency virus (HIV) antibody were reactive. The authors recommend routine FTA-ABS and VDRL screening in patients with uveitis or unexplained ocular inflammation. They also recommend testing for HIV antibody in luetics and aggressive treatment with high-dose aqueous penicillin for syphilis. PMID- 2243679 TI - Acute syphilitic posterior placoid chorioretinitis. AB - Six patients with evidence of secondary syphilis presented with visual loss in both eyes caused by large, placoid, yellowish lesions with faded centers at the level of the pigment epithelium in the macula and juxtapapillary areas. All eyes had vitreitis. All of the lesions showed a similar fluorescein angiographic pattern of early hypofluorescence and late staining. Five patients had mucocutaneous lesions typical of secondary syphilis. All five patients treated with antibiotics had prompt improvement in visual function and resolution of the fundus lesions. The ophthalmoscopic and angiographic appearance of these posterior fundus lesions was sufficiently characteristic to suggest a diagnosis of secondary syphilis. Modification of the host response to syphilis by human immune deficiency virus (HIV) infection may be partly responsible for this peculiar fundus picture. Three of the four patients tested positive for HIV. PMID- 2243680 TI - Indications and results of relaxing retinotomy. AB - The authors report their results of a consecutive series of 40 eyes undergoing relaxing retinotomy during vitrectomy to achieve retinal reattachment for the following indications: proliferative vitreoretinopathy (PVR), 21 eyes (52%); trauma, 10 eyes (25%); diabetic retinopathy, 6 eyes (15%); and expulsive choroidal hemorrhage, 3 eyes (8%). Thirty eyes (75%) had undergone previous vitreoretinal procedures. Extended tamponade was achieved in all cases with either silicone oil (27 eyes, 68%) or long-acting gas (13 eyes, 32%). Retinotomy size ranged from 45 degrees to 360 degrees. Intraoperative retinal attachment was possible in all eyes with 33 (83%) achieving total or subtotal retinal attachment including the macula for 5 months or more. Twenty-seven eyes (68%) achieved 3/200 visual acuity or better and 10 (37%) achieved 20/400 or better. Thirteen eyes (32%) failed to achieve 3/200 visual acuity secondary to recurrent detachment (18%), corneal decompensation (8%), macular dysfunction (5%), and glaucoma (3%). PMID- 2243681 TI - Extensive peripheral retinectomy combined with posterior 360 degrees retinotomy for retinal reattachment in advanced proliferative vitreoretinopathy cases. AB - Posterior 360 degrees retinotomy in conjunction with extensive peripheral retinectomy was necessary for retinal reattachment in 18 eyes. A visual acuity of 20/400 or better was achieved in 22% of the patients; in patients with rubeosis, regression was found in 89%. Of the hypotonus eyes, preoperatively 78% were normotensive postoperatively after removal of anterior proliferative vitreoretinopathy (PVR) covering ciliary epithelium. The major intraoperative complication was hemorrhage, which could be readily controlled. Recurrent retinal detachment (RD) occurred in 39% and reproliferation in 50% of the patients. PMID- 2243682 TI - Experimental retinal branch vein occlusion in miniature pigs induces local tissue hypoxia and vasoproliferative microangiopathy. AB - In miniature pigs, retinal veins were experimentally occluded using argon laser coagulation. Microvascular modifications leading to retinal hemorrhages and retinal edema were observed some hours after the occlusion. These lesions resolved progressively within 3 weeks after the occlusion, but in most cases ischemic retinal territories persisted. Preretinal partial pressure of oxygen (PO2) measurements, using double barrelled O2-sensitive microelectrodes, showed that all the ischemic areas were indeed hypoxic. In half of the experiments, preretinal and intravitreal new vessels grew on the ischemic territories. Tissue hypoxia appears to be a key step in triggering neovascularization. However, the critical level of hypoxia was not determined. PMID- 2243683 TI - Scatter photocoagulation restores tissue hypoxia in experimental vasoproliferative microangiopathy in miniature pigs. AB - Experimental retinal branch vein occlusion using argon laser photocoagulation in miniature pigs induced the development of ischemic retinal territories associated with preretinal neovascularization. Preretinal partial pressure of oxygen (PO2) measurements on the ischemic territories, using O2-sensitive microelectrodes, established that the ischemic retinal areas were hypoxic. Scatter photocoagulation of these ischemic hypoxic territories restores the local PO2 to the normal values within 2 weeks. Hence, the reported inhibitory effect of photocoagulation on the development of retinal neovascularization could be due to a reversal effect on tissue hypoxia. PMID- 2243684 TI - Longitudinal study of lesions of the posterior segment in onchocerciasis. AB - Onchocerciasis is a major cause of blindness, and much of the blindness due to onchocerciasis is caused by chorioretinitis. Little is known about the progression of lesions in the posterior segment in either untreated or treated disease. The authors studied the progression of onchocercal chorioretinitis in 57 patients from 1 to 3 years. Changes were documented from detailed ocular examinations, fundus photographs, and fluorescein angiograms, and included live intraretinal microfilariae, intraretinal hemorrhages, cotton-wool opacities, intraretinal pigment, white and shiny intraretinal deposits, retinal pigment epithelial window defects, and atrophy. Depigmentation at the edge of chorioretinal scarring progressed at a rate of up to 200 microns per year. Ivermectin or mebendazole treatment did not appear to alter the progress of depigmentation at the edge of chorioretinal scars. These observations suggest that onchocercal chorioretinitis is associated with early changes in the retina and retinal pigment epithelium, and that disease in the posterior segment may progress rapidly. PMID- 2243685 TI - Toxoplasma gondii retinochoroiditis and optic neuritis in acquired immune deficiency syndrome. Report of a case. AB - A 29-year-old man with acquired immune deficiency syndrome (AIDS) was found to have a retinochoroiditis and optic neuritis of his left eye. Results of fundus examination showed inflammatory and hemorrhagic retinal lesions consistent with retinitis due to cytomegalovirus infection. A computed tomographic (CT) scan demonstrated enlargement of the optic nerve. The eye was enucleated and results of histopathologic examination showed retinal necrosis with underlying choroiditis and an optic neuritis. Numerous encysted Toxoplasma gondii organisms were present in the retina and tachyzoites were present in the optic nerve. To the authors' knowledge this is the second histologically documented case of Toxoplasma optic neuritis in a patient with AIDS. PMID- 2243686 TI - Computed tomography in the assessment of the postenucleation socket syndrome. AB - To gain a deeper insight into the cause of the postenucleation socket syndrome, high-resolution computed tomography (CT) was performed in 22 anophthalmic patients before insertion of an intraorbital implant. The anatomy of the normal and the anophthalmic orbits was compared. Computed tomographic scans were made either in the sagittal and the coronal plane or in the sagittal and transverse plane. The authors discovered a sagging and retraction of the superior muscle complex and a downward and forward redistribution of orbital fat. Finally, an upward displacement of the distal end together with a retraction of the inferior rectus muscle was found. These phenomena were measured and appear to cause a rotatory displacement of orbital contents from superior to posterior and from posterior to inferior which is best demonstrated in the sagittal plane. This redistribution of orbital contents can explain the sequelae of the anophthalmic orbit. No signs of orbital fat atrophy could be demonstrated. With this knowledge, the proper treatment of patients with a postenucleation socket syndrome is ascertained. PMID- 2243687 TI - Immunoblastic T-cell lymphoma presenting as an eyelid tumor. AB - A 59-year-old white man presented with an ulcerating mass of the left upper eyelid of 6 months' duration. A biopsy specimen of the tumor was diagnosed as an immunoblastic T-cell malignant lymphoma. The lesion completely regressed after 4000 cGy of cobalt-60 radiation therapy. In the ensuing 33 months, multiple, widespread skin nodules of the same neoplasm developed including a right upper eyelid tumor. To the authors' knowledge, this is the first reported case of an immunoblastic T-cell lymphoma initially manifesting as an eyelid neoplasm. PMID- 2243688 TI - Lateral wall advancement in orbital decompression. AB - Treatment of dysthyroid orbitopathy can be enhanced with a modified craniofacial approach using a lateral wall osteotomy, and anterolateral advancement and osteosynthesis in conjunction with medial and inferior wall orbital decompression. The technique of lateral wall advancement is described, and the results are discussed. While the authors advocate orbital decompression for dysthyroid optic neuropathy, advancement of the lateral orbital wall can easily be performed as an adjunct to the two- or three-wall decompression procedure. Advancement appears to increase the overall decompressive effect by providing a potential space where lateral expansion can occur and by enlarging the bony orbital volume. It also appears to lessen lid retraction and facilitates (and in some cases, obviates) the need for further lid retraction surgery. PMID- 2243689 TI - Assessment of tear drainage after canalicular obstruction using fluorescein dye disappearance. AB - Assessment of tear drainage impairment after monocanalicular obstruction can be difficult. The authors used fluorescein dye disappearance to evaluate tear drainage after experimental obstruction of upper, lower, neither, or both canaliculi in 20 subjects. Marked impairment was noted in all subjects when both canaliculi were occluded (P less than 0.004). Monocanalicular obstruction (either upper or lower) generally resulted in minimal or no impairment, though 10% of subjects showed marked impairment. Fluorescein dye disappearance proved a reliable, rapid method for assessing tear drainage and detecting lacrimal obstruction. PMID- 2243690 TI - The incidence of liability claims in ophthalmology as compared with other specialties. AB - Ophthalmologists continue to share in the professional liability claims that plague the medical profession. Data have been extrapolated from the April 1987 publication of the United States General Accounting Office (GAO) entitled, "Medical Malpractice Characteristics of Claims Closed in 1984." This document presents information pertaining to the comparative incidence of professional liability claims of ophthalmologists with other specialties. PMID- 2243691 TI - Seven hundred medicolegal cases in ophthalmology. AB - Seven hundred medicolegal claims in ophthalmology were reviewed by one ophthalmologist who served as an expert for four decades. The ophthalmologist was personally involved in 620 claims. The 700 cases have been categorized and analyzed. The reasons for the claims and some lessons derived from them are presented. Familiarity with the claims encountered by others may enable ophthalmologists to avoid similar claims. PMID- 2243692 TI - Ophthalmology personnel in risk management. What office personnel need to know to keep you out of trouble. AB - The performance of staff in the ophthalmologist's office will influence the risk that an individual patient may someday file a medical malpractice complaint. Areas of identified risk include improper triage of emergency patients, abandonment, problems in confidentiality, improper maintenance of medical records, and perceived lack of compassion and skill on the part of staff members. PMID- 2243693 TI - The expert witness. AB - The rewards for suits for medical negligence have generated a service industry for plaintiff's lawyers. The provision of "experts" for a contingency fee and the solicitation of plaintiff's attorneys by some physicians to serve as "experts" for large fees may result in highly biased and inaccurate testimony. Ethical expert witness testimony involves knowledge of the commonly accepted principles of treatment at the time of the alleged negligence, recognition of possible multiple accepted avenues of therapy, and testimony that educates the court and jury rather than obfuscates and distorts for personal gain. PMID- 2243694 TI - [The importance of Doppler echocardiography in the differential diagnosis of causes of neonatal cyanosis]. AB - The authors report 329 dopplerechocardiographic examinations performed on 167 term and preterm newborn babies presenting cyanosis. Seventy-six congenital heart defects were detected among their patients, 12 of whom were operated without heart catheterization, according to the ultrasound finding. The diagnosis of ten inoperable heart diseases established without hemodynamic examination was confirmed by autopsy. Cyanosis due to cardiac and pulmonary abnormalities without congenital heart defect was diagnosed in 38 patients. Persistent ductus arteriosus was found in 45 very lowbirth-weight premature babies. Doppler echocardiography proved to be a major advance in the differential diagnosis of newborn cyanosis and in choosing appropriate therapy. PMID- 2243695 TI - [Lymphogranuloma venereum]. AB - A young couple's case of Lymphogranuloma venereum was reviewed by the authors. They described the case's medical history and then they reviewed those tissue- cultural and immunological--methods which made sure the assumed diagnose by clinical and histological datas. The symptomless and painless wife's subclinically process was discovered. They called attention for that in spite of correct diagnose rareness the illness occurs more often. On the pathological process was influenced therapeutical by tetracyclin. We can treat successfully with tetracyclin the so called "blind-cured' cases. This situation made comfortable the diagnostics activity and it contributed to the wrong surface that the illness occurs rarely. PMID- 2243696 TI - [Prenatal diagnosis of cystic fibrosis based on DNA analysis]. AB - 25 families at risk of having a child with cystic fibrosis have been counselled about prenatal diagnosis by the use of linked DNA probes (xV-2c, pCS.7, Met D, Met H, pJ3.11 and KM 19). In 20 families one or more informative probes, in 3 cases only partly informative probes were found, and in 2 families there was no informative probe at all. In 9 cases prenatal diagnosis have been performed, 6 children have been born and confirmed to be free from cystic fibrosis and 3 terminations were carried out because of prenatal prediction of cystic fibrosis. PMID- 2243697 TI - [The role of intraoperative angioplasty performed simultaneously with reconstructive vascular surgery]. AB - 21 arterial lesions were dilated intraoperatively in conjunction with primary vascular reconstructive procedures. Of these, five involved the iliac vessels, fourteen the femoropopliteal segment, one the subclavian artery and one the common carotid artery. 19 intraoperative balloon dilatations were successful and two were unsuccessful. Only one catheter-related complication were noted, it was a perforation of the wall of the artery caused by guidewire. No deaths occurred as a result of the combined procedure. Attention is drawn to the advantage of the intraoperative balloon dilatation and the authors recommend it on adequate conditions and correct indication. PMID- 2243698 TI - [A case of hybrid acute leukemia in a a child]. AB - Hybrid acute leukaemia is characterized by the presence of lymphoid and myeloid markers in a single cell or in different blast cell subpopulations of the same patient. Authors report on a case of a 14-yr-old girl with hybrid acute leukaemia. Immunofluorescent analysis revealed CD 14, CD 10, CD 19 and HLA-DR antigens in the cell suspension isolated from peripheral blood of the patient. Because of the excess of FAB M1 type blast cells, the patient was treated according to IGCI-1984 protocol. Remission was not achieved despite combined cytotoxic treatment and patient died within 4 weeks following admission. The poor outcome of the disease agrees well with literature data. Hybrid acute leukaemia represents a challenge for the clinical science. PMID- 2243699 TI - [The effect of Hungarian pediatrics on the international medical sciences]. PMID- 2243701 TI - [Forecasting in medical meteorology]. PMID- 2243700 TI - [How did Tamas Jordan discover the cause of the 1577 disease outbreak in Brunn?]. PMID- 2243702 TI - [Myasthenia gravis: results of thymectomy in 550 patients]. AB - Report is giving on 550 myasthenic patients who underwent thymectomy during the last 18 years. Results of thymectomy are analysed in separate groups and according to different aspects, including thymic tumours (13.63%), operations in childhood (9.64%), and combined cases (11.1%). The results are evaluated according to Disability Status Scale based on a point-system. Successive improvement was observed in the three series concerning the results of operation. Childhood myasthenia gravis gave the best results but thymectomy was beneficial in the combined group, in long-lasting myasthenia and in tumourous cases, too. There are quite a few factors influencing the results, such as the interval between the disease onset and thymectomy, the patients' age, thymoma, crisis danger and the activity of the thymus gland reflecting in the number of the germinative centres. The more active the thymus, the better the results. PMID- 2243703 TI - [Diagnosis and treatment of non-immune hydrops foetalis]. PMID- 2243704 TI - [Survival rate and follow up studies of very low birth weight (less than 1000 g) premature infants]. AB - The Neonatal Intensive Care Unit (NICU) at the Department of Pediatrics, University Medical School Pecs had been established 11 years ago. 219 premature infants who weighed 1000 g or less were admitted to the NICU between Jan. 1978 and Dec. 1988. The authors analysed the hospital records of there patients and found a marked increase in survival rates during the last five year period. The data presented strongly suggest that improvement of obstetric care, development of respiratory and fluid therapy, the increasing experience of hospital staff caring for the infants are the main factors contributing to improved results. At the same time the adverse effects of transportation from the referring institution are well demonstrated. The main causes of death remained the same over the 11 years studied. The number and severity of acute and late complications decreased markedly. The intensive care of very low birth weight infants is becoming increasingly expensive. However the growing expenditures are justified by increasing life expectancy of patients and the expected better quality of life among survivors. PMID- 2243706 TI - [The beginnings of ethno-psychological and socio-psychiatric studies of the ethnic groups of Transylvania at the turn of the century]. PMID- 2243705 TI - [Management of gas gangrene in Hungary during 1979-1988 based on data from Public Health Centers]. AB - Authors present data on the therapy of 223 gas gangrene cases between 1979-1988, a ten years period, based on the reports of Public Health Stations in Hungary. Of the 223 patients 150 died, thus lethality was 67.3%. In lack of surgical intervention there was no chance of survive. Merely wound exposure resulted in a much higher fatality rate than necrectomy of the wound. Local hydrogen-hyperoxide treatment improved survival essentially. Specific antitoxin therapy did not influence the survival rate. The effect of a single antibiotic was poor; combined antibiotic treatment gave a significantly better result. As for combination, the most effective were erythromycin, the lincosamids and chloramphenicol. According to the data presented, it would be possible to reduce to the half the fatality rate of gas gangrene in Hungary. PMID- 2243707 TI - [Who was the first Hungarian translator of Hahnemann's "Organon"?]. PMID- 2243708 TI - [Changes in the stress-provoked septal Q wave]. PMID- 2243709 TI - [Creation of a gastric pouch during total gastrectomy. Remarks on a journal summary]. PMID- 2243710 TI - [Letter to a future colleague (guidelines of radiology)]. PMID- 2243711 TI - Diagnosis--100% accurate; treatment--100% successful. PMID- 2243712 TI - New president emphasizes unified action. PMID- 2243713 TI - A review of horse-drawn buggy accidents. PMID- 2243715 TI - Practice parameters in medicine. Subcommittee on Practice Parameters, Council on Medical Economics. PMID- 2243714 TI - Preprocedure review changes. PMID- 2243716 TI - Benefits of antiretroviral therapy. PMID- 2243717 TI - Your office manager: new key to success. The Health Care Group. PMID- 2243718 TI - Debunking myths in indigent health care. PMID- 2243719 TI - Little-known methods effective on stress. PMID- 2243720 TI - Regression to the mean in medicine. PMID- 2243721 TI - Position paper on AIDS/HIV infection. Pennsylvania Public Health Association. PMID- 2243722 TI - How many rich doctors are there? PMID- 2243723 TI - Three-dimensional assessment of surgical excision margins in skin tumor resection biopsies. AB - A new technique for the assessment of adequacy of surgical margins of excision in skin tumor resection biopsies is described. The technique essentially consists of staining the whole fresh or fixed biopsy tissue in eosin followed by Mayer's hematoxylin. Following staining, the epidermal perimeter of the skin ellipse and the deep surgical margin can be assessed using a stereo-microscope. Should areas suspicious of inadequate excision be identified these may be confirmed by directed frozen or paraffin section. PMID- 2243724 TI - Exaggerated reaction to insect bites in patients with chronic lymphocytic leukemia. Clinical and histological findings. AB - We report three patients with chronic lymphocytic leukemia with unusual vesiculo bullous skin eruptions on exposed areas which were more commonly noted in spring and summer. The lesions appeared to be due to insect bites and could be differentiated from other causes on the basis of histological, immunohistological and clinical features. There was no correlation between the occurrence of the skin eruptions, disease status and treatment modalities. Exaggerated cutaneous reaction to insect bites should be considered as a cause of vesiculo-bullous lesions in patients with chronic lymphocytic leukemia. PMID- 2243725 TI - A study of serum free medium culture on the cloning efficiency of human bone marrow myeloid and erythroid progenitors. AB - Thirteen different combinations of serum-free media were tested to assess their suitability to replace serum containing medium for in vitro culture of human hemopoietic progenitors (CFU-GM and BFU-E). Bone marrow samples from patients with and without hematological diseases were tested. All tested media supported the growth of CFU-GM and BFU-E colonies, however our results have shown that the cloning efficiency of all commercially available serum-free media tested was lower (mean 18% and 12% of controls for CFU-GM and BFU-E respectively) and the colony size was smaller than those in serum-containing medium. In the serum-free cultures, there was no linear relationship between the colony numbers and cell concentration plated. Depletion of T-lymphocytes and monocytes did not improve the cloning efficiency of the serum-free medium culture. Furthermore, the addition of high concentration of insulin, transferrin and other supplements to the serum-free media did not improve the cloning efficiency. These results have indicated that the currently available commercial serum-free media do not provide optimal requirements for hemopoietic progenitor cell cultures and that other factors contained in serum are essential for their optimal growth. PMID- 2243726 TI - Red cells suspended in a phosphate-fortified additive: biochemical enhancement and longer storage. AB - When compared to our current storage regime, an additive solution, with 75 mM inorganic phosphate, improved certain biochemical and morphological parameters measured in suspensions of packed red cells throughout 49 days of liquid storage. In particular, the mean ATP level of 20 donations stored with the high phosphate additive was consistently and significantly higher than in standard (n = 6) suspensions. The increased amount of inorganic phosphate and the higher pH of the new additive stimulated ATP production and provided better pH buffering than the standard solution currently in use. Although survival study results indicated adequate 24h survivals for erythrocytes stored for 42 days with the new solution, after 49 days storage, the mean 24h survival of autologous erythrocytes was only 58 +/- 7% (n = 6). PMID- 2243728 TI - An improved screening technique for isolation of Nocardia species from sputum specimens. AB - Three selective isolation media and the paraffin baiting technique were compared with conventional culture (Sabouraud dextrose agar without antibiotic supplement) for the ability to grow and detect nocardiae from simulated sputum specimens. Modified Thayer-Martin medium, incorporating vancomycin, colistin, nystatin and trimethoprim as selective agents, produced the highest recovery rate and with the greatest suppression of normal respiratory tract flora. A clinical evaluation using a screening programme devised for a busy diagnostic microbiology laboratory was performed on 1600 sputum specimens. Inoculating sputum on modified Thayer Martin medium and extending the initial incubation period of 3 days at 35 degrees C under 10% carbon dioxide to a further 3 weeks at room temperature in a candle jar, led to the diagnoses, which otherwise would have been missed, of pulmonary nocardiosis in 3 patients and pulmonary infections due to Neisseria meningitidis, Pseudomonas cepacia, and Serratia marcescens in a further 22 patients. PMID- 2243727 TI - Lymphocyte subsets in granulomas of human tuberculosis: an in situ immunofluorescence study using monoclonal antibodies. AB - The immunophenotypic characteristics of lymphocyte subpopulations in tissue lesions of human tuberculosis were investigated in 18 cases. Frozen sections of affected cervical lymph nodes were stained with a panel of monoclonal antibodies using avidin-biotin immunofluorescence technique. The mean percentage of cells staining with different antibodies was as follows: CD3 44%; CD4 43%; CD8 36%; HLA DR 86%; and IgM 29%. The mean CD4/CD8 ratio was 1.3:1. Leu7 and CD1 staining cells were very sparsely distributed in the granulomas. Thus, infection with tuberculosis is associated with a predominantly T cell infiltrate in lesional tissues. The proportion of CD4 positive (helper/inducer) cells at these sites is much lower than that seen (i) in the normal circulation, (ii) in reactive lymph nodes and (iii) at the site of purified protein derivative (PPD) injection in healthy tuberculin-responsive individuals. PMID- 2243729 TI - Evaluation of a selective medium for the isolation and differentiation of Haemophilus influenzae and Haemophilus parainfluenzae from the respiratory tract of chronic bronchitics. AB - Respiratory tract specimens from chronic bronchitic patients were cultured for Haemophilus species on conventional chocolate agar and a modified sucrose medium in order to determine the accuracy of the new medium in differentiating Haemophilus influenzae from Haemophilus parainfluenzae strains. Haemophilus influenzae biotypes II and III and Haemophilus parainfluenzae biotypes I and II were found to be the predominant strains isolated from the respiratory tract. The modified sucrose medium was found to be a rapid and reliable means of differentiating Haemophilus influenzae from Haemophilus parainfluenzae by sucrose fermentation, on initial isolation. PMID- 2243731 TI - Ki-1 positive anaplastic large cell lymphoma. PMID- 2243732 TI - Child health in 1990: the United States compared to Canada, England and Wales, France, the Netherlands, and Norway. Proceedings of a conference, Washington, DC, March 18 and 19, 1990. PMID- 2243730 TI - Experience of a molecular genetics service in prenatal diagnosis by DNA analysis. AB - Prenatal diagnoses of the genetic disorders alpha, beta thalassemia, HbS, Hb Lepore, hemophilia and cystic fibrosis were sought in 88 cases. Six unsuccessful attempts at diagnosis resulted from DNA polymorphisms which were only 50% informative (four cases) and prenatal diagnoses which had been undertaken before it was known whether DNA polymorphisms in family studies were informative (two cases). The most frequent indications for prenatal diagnosis were the hemoglobinopathies although requests for exclusion of cystic fibrosis formed the majority during 1989. Strong linkage disequilibrium between the cystic fibrosis defect and its associated DNA polymorphisms facilitated detection of this disorder. Late presentations among patients with beta thalassemia and hemophilia and the necessity for more specialised genetic counselling were the commonest problems encountered. PMID- 2243733 TI - Child health in Canada. PMID- 2243734 TI - Child health services in England and Wales: an overview. AB - Child health services in England and Wales are rendered largely through the National Health Service and Social Security. The activities of local authorities are also important to child health. The structure and scope of services offered children by each of these is presented and discussed, with special attention to changes anticipated during the next 2 years. The care of children is integrated into the system serving all ages, so that services are difficult to evaluate and resources are shared with other groups. Health policy for children is fragmentary, although encouraging trends are visible in the evolution of existing policy. The impact of impending changes in hospital, community, and general practitioner services on the care of children is unclear at this time. PMID- 2243735 TI - Child health care policy and delivery in France. AB - Medical and social protection of mothers, infants, and children began in France more than a century ago. A number of laws and regulations have improved the system, which is discussed in detail. The discussion includes an overview of health policy, service delivery, and the financing of care. Is the current French system of Maternal and Child Health responsible for the good health of today's children? This question is addressed through selected examples. Finally, failures and short-comings of the system are described, including the persistence of underserved groups, unequal access to care, and other problems. Solutions are feasible, and some are now being implemented. PMID- 2243736 TI - Youth health care in The Netherlands: a bird's eye view. AB - In the context of the conference on cross-national comparisons of child health, a short overview is given of youth health care in the Netherlands. After a brief explanation of the financing of the Dutch health care system, trends in child mortality are shown. A short description is presented of obstetrical care, which features independent midwives and 35% home deliveries; the organization of well baby clinics, which provide for 10 visits in the first 15 months and care for 95% of all children; and the school health services, which cover nearly all children. PMID- 2243737 TI - Children in the Norwegian health care system. AB - Norway is a large, sparsely populated country with a long tradition of socialized health care. The health status of Norwegians is good, with life expectancy among the highest in Europe. Indicators of infant health are also good, although not among the best. Health services in Norway are in principle free of charge to all citizens, and the current health expenditure is about 6.8% of the Gross National Product. Preventive and curative pediatric services account for only 3% of this total. The structure of Norwegian health and social services is presented in this discussion, both in general terms and with particular attention to services for children. PMID- 2243739 TI - Preventive care for children: immunization in England and Wales. AB - Immunization rates against common, notifiable diseases of childhood have improved steadily in England and Wales, although the 90% target rates for 1990 have not been achieved. The organization of the immunization program is described, with attention to service delivery, mechanisms of assurance, and consideration of the remaining barriers to further improvement in coverage. PMID- 2243738 TI - Immunization coverage among preschool children: the United States and selected European countries. PMID- 2243740 TI - The national immunization program of The Netherlands. AB - After a brief explanation of the immunization policy in the Netherlands, the national immunization program is described, with special attention given to coupling of the municipal population records with a computerized database of individual immunization records at the provincial level. The Dutch program achieves coverage rates greater than 90% for all routine immunizations. Participation in the program is free of charge to every child living in the country up to the age of 13 years, but there is no obligation or requirement to be immunized. Financing of the program is also discussed. PMID- 2243741 TI - Immunizations in the United States. PMID- 2243742 TI - Excess injury mortality among children in the United States: comparison of recent international statistics. AB - Using data from the National Center for Health Statistics and the World Health Organization, child injury death rates in the US were compared to those of Canada, England and Wales, France, Netherlands, and Norway. Except for the 1981 Canadian figure, overall US childhood injury mortality was greater than childhood injury mortality rates of all countries studied during each year from 1980 to 1986. Injury mortality steadily declined in most other countries, whereas the US rate appears to be increasing. Attention to specific causes reveals that much of the difference is explained by motor vehicle injuries and homicide, but in every childhood age group US death rates due to drowning, firearms, homicide, poisoning, and fire are among the highest. Excess US injury mortality is largely attributable to deaths among children younger than 5 and older than 14 years of age, the most vulnerable groups in all countries. Especially high rates among US minorities account for little of the observed differences; for many injuries, the mortality rate of US nonblacks is several times those reported by the comparison nations. Behavioral strategies are inadequate to deal with excess death rates of this magnitude. Limiting exposure through regulation of handguns, greater use of public transportation, and affordable and accessible day care are among the measures that should be implemented. PMID- 2243743 TI - Unintentional injury mortality in Canada. PMID- 2243744 TI - Unintended injuries in children: the French situation. AB - The French situation with respect to mortality from unintentional injuries in children is far from satisfactory. International comparison is made difficult by statistical bias, but although excess injury mortality is decreasing in France, rates are higher than in most advanced European countries. Many regulations have been enacted during the past 30 years to reduce the economic and social burden of injuries, but political will is insufficient to establish a consolidated national program and enforcement of existing legislation is inadequate. Evaluation of preventive and educational programs is less than optimal; many attempts have not met basic methodologic requirements. The situation is improving, partly because of growing social concern. New regulations are in preparation, but solution of this major public health problem also demands behavioral change, which is much more difficult to effect than other measures. Greater commitment to research, proper evaluation of sound programs, and enforcement of existing law doubtless would reduce the excess morbidity and mortality resulting from unintended injuries to children. PMID- 2243745 TI - Childhood injuries: where we are. AB - In this paper we present the leading causes of fatal childhood injury in the United States. We examine three types of explanations for why injury rates are so high in the United States compared with what they could be and actually are in a number of industrialized European countries. Our conclusions are based on what we learn when we look at specific injury problems and apply that knowledge to the field of childhood-injury prevention as a whole. To decrease the number of fatal injuries to children, we should: 1. Recognize injuries as a major public health problem. Injuries have been perceived not as problems to be solved but as "accidents" which are determined by fate, not understandable, and consequently not preventable. In addition, injuries have not been addressed in the multidisciplinary fashion that typifies the successful public health approach to other problems. 2. Address intentional injury as part of the problem. Intentional injury has been treated as a separate field entirely and not addressed scientifically as a public health problem. One consequence of this is that injuries due to firearms have been addressed most frequently as a problem of "unintentional injury." As a result, 93% of all firearm injuries, ie, those which are intentional, have not been studied or addressed adequately. This situation is like studying motor vehicle injuries but excluding drunk driving and speeding as contributing factors, or like studying acquired immunodeficiency syndrome but ignoring anal intercourse or intravenous drug use. 3. Develop and support organizations that can plan and coordinate effectively a national approach to injury control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2243746 TI - Postneonatal mortality in the United States: an international perspective. AB - The international standing of the United States in postneonatal mortality has deteriorated from third in 1950 to sixteenth in 1986. The high rate among United States blacks is not the reason for the poor United States standing: ten other countries had lower rates than that for United States whites. Recent trends show a slowdown in the decline in postneonatal mortality between 1970 to 1981 and 1981 to 1986 in Canada, England and Wales, Netherlands, and the United States. Norway actually experienced increases during the latter period. Only France showed an acceleration in its decline during the 1980s. Canada has maintained the most rapid rate of decline between 1950 and 1986. Although all countries examined here reported Sudden Infant Death Syndrome as the leading cause of postneonatal deaths, there was twofold variation among the countries in the Sudden Infant Death Syndrome rate. Similarly, congenital anomalies, the second leading cause of death, showed a 50% range in mortality rates. Infections accounted for less than 10% of all postneonatal deaths. A reasonable approach to assessing the magnitude of preventable mortality in the postneonatal period is to use mortality from all causes except congenital anomalies among normal birth weight infants. United States whites had a lower "preventable" postneonatal mortality rate than Denmark, England and Wales, and Scotland, but a higher rate than Sweden. United States blacks, on the other hand, had by far the highest rates. Disaggregating the United States rates further into three broad maternal risk groups, there was a doubling of rates with increasing level of maternal risk. About half the postneonatal deaths among normal birth weight infants could be prevented if the entire population experienced the rates of the lowest maternal risk group. PMID- 2243747 TI - Postneonatal infectious disease mortality: the French situation. AB - Mortality caused by infectious and parasitic diseases represents a limited part of all postneonatal deaths in France, which have been stable for the past decade. This component is worthy of careful analysis because it is at least partially preventable. Statistics are presented and interpreted, with discussion on which disorders should be included in assessing the impact of infection on morbidity and mortality. Figures and international rankings change according to the inclusiveness of the definition chosen. There is need for epidemiologic and statistical research to make comparisons of mortality more clear. Morbidity is also important because of high incidence, frequent hospitalization, and a heavy social cost. Policy and services in France that relate to control and treatment of infection are described, as are shortcomings that call for further efforts. PMID- 2243748 TI - Postneonatal mortality in Norway: a study of recent trends and comparison with other mortality rates in Norwegian children. AB - Postneonatal mortality in Norway decreased rapidly from 1956 to 1980 but subsequently remained stable. In recent years the postneonatal death rate appears to be increasing, primarily due to greater numbers of deaths attributed to the Sudden Infant Death Syndrome. During the same period, mortality among older children has also decreased, with the decline evident in all leading causes. Only among people aged 15 to 19 years have recent trends been less than encouraging, with the number of fatal traffic accidents in particular remaining stable or increasing. Although there is room for continued improvement, the widely held belief that the health status of Norwegian children is good is supported by the trends in mortality. PMID- 2243749 TI - Postneonatal mortality: a performance indicator of the child health care system. PMID- 2243750 TI - Children with special needs in England and Wales: the care of hearing impairment, myelomeningocele, and adolescent pregnancy. AB - Services for children with special needs in England and Wales are described briefly, with attention to the services provided by the National Health Service, local authorities, the social security system, and voluntary organizations. For illustrative purposes, particular reference is made to children with hearing impairments and myelomeningoceles. A separate account is given of the provision for pregnant adolescents, again addressing services provided by all major sources of assistance. PMID- 2243751 TI - Children with special needs in The Netherlands: impaired hearing, adolescent pregnancy, and myelomeningocele. AB - In the Netherlands, treatment and management of children with special needs is characterized by the absence of financial barriers to care and the existence of a number of specialized services. For hearing-impaired children, there are special audiologic centers and special schools. Adolescents at risk of unintended pregnancy are protected through education and a dedicated system of family planning clinics. Children with multiple handicaps, such as those associated with myelomeningocele, face greater difficulties but still have an array of services available to them at little or no cost. Families are sheltered from excessive expense through social insurance. PMID- 2243752 TI - Children with special health needs: a United States perspective. PMID- 2243753 TI - Hemispheric differences are found in the identification, but not the detection, of low versus high spatial frequencies. AB - The processing of sine-wave gratings presented to the left and right visual fields was examined in four experiments. Subjects were required either to detect the presence of a grating (Experiments 1 and 2) or to identify the spatial frequency of a grating (Experiments 3 and 4). Orthogonally to this, the stimuli were presented either at threshold levels of contrast (Experiments 1 and 3) or at suprathreshold levels (Experiments 2 and 4). Visual field and spatial frequency interacted when the task required identification of spatial frequency, but not when it required only stimulus detection. Regardless of contrast level (threshold, suprathreshold), high-frequency gratings were identified more readily in the right visual field (left hemisphere), whereas low-frequency gratings showed no visual field difference (Experiment 3) or were identified more readily in the left visual field (right hemisphere) (Experiment 4). Thus, hemispheric asymmetries in the processing of spatial frequencies depend on the task. These results support Sergent's (1982) spatial frequency hypothesis, but only when the computational demands of the task exceed those required for the simple detection of the stimuli. PMID- 2243754 TI - Spatial contingency and the McCollough effect. AB - On the basis of a conditioning analysis of the orientation-contingent color aftereffect (McCollough effect, ME), orientation stimuli become associated with simultaneously presented chromatic stimuli. This account suggests that decreasing the contingency between the grid orientation and color should decrease the strength of the aftereffect. Results of previous research indicate that decreasing the temporal contingency (by presenting homogeneous chromatic stimuli between presentations of chromatic grids) does not decrease the ME. However, it has been suggested that the appropriate contingency-degradation procedure would involve decreasing spatial (rather than temporal) contingency. That is, the illusion should be attenuated by extending the color beyond the confines of the grid. Contrary to this hypothesis, the results of the present experiments provide no evidence that decreasing the spatial contingency between grid and color decreases the ME; rather, the aftereffect is increased by such a manipulation. PMID- 2243756 TI - Perceptual integration of tertiary taste mixtures. AB - Integration psychophysics was used to explore the taste perception of mixtures of sucrose, fructose, and citric acid. Three levels of each stimulus were varied in a 3 x 3 x 3 factorial design. Subjects rated total intensity, sweetness, and acidity of the 27 mixtures on graphic rating scales. Consistent with earlier work, the perceived total intensity of the tertiary mixtures was found to be dictated by the intensity of the (subjectively) stronger component alone (i.e., either the integrated sweetness or the acidity, whichever was the more intense). In contrast, the sweetness and acidity of the mixture were susceptible to mutual suppression: Sweetness suppressed acidity, acidity suppressed sweetness. There was, however, a difference between sucrose and fructose in their interactions with citric acid, fructose being the more susceptible to suppression. This selectivity of suppression indicates that the two sweetnesses could not have been inextricably integrated. Implications for taste coding are discussed, and the findings are reconciled in terms of two separate coding mechanisms: one for taste intensity, another for taste quality. PMID- 2243757 TI - Identifying contours from occlusion events. AB - Surface contours specified by occlusion events that varied in density, velocity, and type of motion (rotation or translation) were examined in four experiments. As a fourth experimental factor, there were both figure-motion trials (the occluding surface moved over a stationary background) and background-motion trials (the background moved behind a stationary surface) in each experiment. Displays contained line patterns and rotary motion (Experiment 1), line patterns and translatory motion (Experiment 2), textured surfaces and rotary motion (Experiment 3), and textured surfaces and translatory motion (Experiment 4). Results indicate that contour identifications are more accurate with translation than with rotation, and that background-motion trials are generally easier than figure-motion trials. Although density in all experiments affected identifications in both background- and figure-motion trials, velocity did so in Experiment 4 only. In Experiments 1, 2, and 3, velocity affected identifications in background-motion trials but not in figure-motion trials. In Experiments 3 and 4, the rate of accretion and deletion of texture was a poor predictor of identification accuracy. These results are not consistent with previous accounts of contour perception from occlusion events, and may reflect an involvement of ocular pursuit as a mechanism for registering contour information. PMID- 2243755 TI - On the perception of speech from time-varying acoustic information: contributions of amplitude variation. AB - The cyclic variation in the energy envelope of the speech signal results from the production of speech in syllables. This acoustic property is often identified as a source of information in the perception of syllable attributes, though spectral variation can also provide this information reliably. In the present study of the relative contributions of the energy and spectral envelopes in speech perception, we employed sinusoidal replicas of utterances, which permitted us to examine the roles of these acoustic properties in establishing or maintaining time-varying perceptual coherence. Three experiments were carried out to assess the independent perceptual effects of variation in sinusoidal amplitude and frequency, using sentence-length signals. In Experiment 1, we found that the fine grain of amplitude variation was not necessary for the perception of segmental and suprasegmental linguistic attributes; in Experiment 2, we found that amplitude was nonetheless effective in influencing syllable perception, and that in some circumstances it was crucial to segmental perception; in Experiment 3, we observed that coarse-grain amplitude variation, above all, proved to be extremely important in phonetic perception. We conclude that in perceiving sinusoidal replicas, the perceiver derives much from following the coherent pattern of frequency variation and gross signal energy, but probably derives rather little from tracking the precise details of the energy envelope. These findings encourage the view that the perceiver uses time-varying acoustic properties selectively in understanding speech. PMID- 2243759 TI - Inhibitory tagging in visual search: a failure to replicate. AB - Klein (1988) reported that increased reaction times for the detection of small light probes could be used as an indicator of inhibitory tagging of rejected distractors in serial visual search tasks. Such a paradigm would be very useful in the study of the mechanics of visual search. Unfortunately, we cannot replicate the result. In this study, we found that probe reaction times were elevated at all distractor locations, relative to empty locations, following both parallel and serial search tasks. This appears to be a forward masking effect. PMID- 2243758 TI - The size-weight illusion in 2-D nonlinear psychophysics. AB - An extension of unidimensional nonlinear psychophysics is postulated by using forms of cross-coupling between the parameters of the two single-channel recursions, which have already been shown to model some perceptual phenomena. The size-weight illusion is shown to be reproducible in the topology of its relations, and it is suggested that some so-called illusions are in fact the natural consequences of nonlinear cross-coupling. The conditions that produce the illusion involve partially compensating the cross-coupling of sensory dimensions, and a second equilibrium with no cross-coupling, resembling simpler veridical perception, also exists in the behavior of some subjects. PMID- 2243761 TI - The Bourdon illusion occurs with straight-, right-angle-, and parallel-edge figures. AB - The Bourdon illusion is the apparent bentness of the straight edge of a figure consisting of two elongated triangular components arranged apex to apex. In three experiments, the illusion was shown to occur in the opposite direction, with the components arranged base to base. It was also shown to occur with the component edges at right angles and parallel. With the edges at right angles, the illusion also occurred in one direction when the components were apex to apex and occurred in the opposite direction when they were base to base. Supplementary observations indicated that the illusion is stronger when the components are relatively small and widely separated and eliminated when one of the two edges is curved. PMID- 2243760 TI - Image rotation of misoriented letter strings: effects of orientation cuing and repetition. AB - Three experiments were designed to investigate whether the characteristic function relating response time to stimulus orientation reflects the observer imagining the rotation of the stimulus to upright (the "image rotation" hypothesis) or rotation of an internal reference frame in response to the misoriented stimulus (the "frame rotation" hypothesis). Identification times in response to misoriented words were measured in Experiment 1, whereas in Experiments 2 and 3, lexical decision times in response to misoriented letter strings were measured. Trials occurred in blocks; words within a block were presented at the same orientation. It was argued that this mode of presentation would facilitate the use of a frame rotation strategy by allowing for a gradual readjustment of an internal reference frame. The characteristic "mental rotation" function was observed in all three experiments. However, the data indicated that observers continued to imagine the rotation of the word to upright in each trial; there was no evidence of readjustment of an internal reference frame. An additional finding of interest occurred in Experiment 1, in which observers identified the same set of misoriented words across two sessions. The identification times were faster, and the slope of the mental rotation function was lower, in the second session. These results are discussed as in relation to the image rotation hypothesis of mental rotation and to "instance-based skill acquisition" (Masson, 1986) in word recognition. PMID- 2243762 TI - Evidence for early selection: precuing target location reduces interference from same-category distractors. AB - In this study, we evaluated whether uncertainty about target location and category overlap between the target and the flankers played a role in recent findings (Miller, 1987) of semantic interference of irrelevant stimuli. In each of four testing conditions, subjects were required to identify a target letter surrounded by irrelevant flankers whose identity predicted the correct response. We varied (1) whether or not the target location was precued, and (2) the flanker's category (digits vs. letters). We found a substantial effect of letter flankers when subjects were uncertain of the precise target location. However, this effect was greatly attenuated when attention was predirected to the target location. Similarly, a reduced flanker effect was observed when the flankers (digits) belonged to a different semantic category than the target. However, when the target location was precued, no effect of the semantic congruity of target and flankers was found. Coupled with previous research, these findings converge in establishing that both failures to maintain attention on the target location and the semantic congruity of target and flankers modulate the size of the effects from irrelevant stimuli. These results are discussed in the context of early and late selection views of selective attention. PMID- 2243763 TI - Electrocutaneous spatial integration at threshold: the effects of electrode size. AB - Five experiments were carried out to investigate the effects of electrode size on threshold for current pulses that flowed between the ventral and dorsal sides of the right forearm. The main result was that the total current threshold decreases as the size of the cathode and anode increases at least up to 15 mm in diameter. To account for this finding, a neural summation model was proposed, assuming that the central nervous system sums up neural impulses discharged near the conduction paths under electrodes. It was also found that the current flowing from the dorsal to the ventral side provided lower thresholds and more stable localization than the opposite flow of current did. This finding suggested that current threshold and its perceived locus are determined by both the body site on which electrodes were placed and the relative polarity that was assigned to electrodes. PMID- 2243764 TI - Negative priming in same-different matching: further evidence for a central locus of inhibition. AB - Responses to recently ignored information may be slower or less accurate than responses to information not recently encountered. Such negative priming effects imply that the mechanism of selective attention operates on unattended, as well as attended, information. In the present experiment, subjects judged the second and fourth letters of five-letter strings (e.g., BABAB) as "same" or "different." Responses were slower when a target letter was identical to the distractors presented in the immediately preceding trial. This effect did not depend on which response was required on the current or preceding trial. The results suggest that ignored information is functionally disconnected from the response system as a whole, rather than from a specific response. PMID- 2243765 TI - Relationship of induced motion and apparent straight-ahead shifts to optokinetic stimulus velocity. AB - Induced motion (IM) of a fixated spot stimulus and shifts of the apparent straight-ahead (ASA) from the objective median plane were studied as a function of the velocity of a full-field optokinetic background stimulus. Both IM and ASA were influenced similarly by changes in stimulus velocity. The magnitude of both responses, averaged across subjects, increased to a peak level with background velocities of 40-80 deg/sec and decreased at higher velocities. Individual subjects differed with respect to the precise functions by which IM and ASA shifts were related to stimulus velocity. However, for individual subjects, the effects of velocity on IM and ASA shifts were typically highly correlated. Although IM is correlated with shifts of ASA in the opposite direction, the magnitude of the ASA shift is insufficient to account for the observed IM. PMID- 2243766 TI - [Tumors of the posterior hard palate]. AB - The palatal mucosa is a representative area when reviewing etiology of the wide variety of oral tumours. The most important are of cystic, neoplastic or inflammatory nature. A case of malignant lymphoma occurred as a firm, painless swelling in the lateral posterior hard palate in a 69 year old woman. The tumour was initially diagnosed and treated as an abscess. Weeks later the swelling persisted and the patient was referred to the Department of oral surgery and oral medicine. University of Bergen. Incisional biopsy revealed the true nature of the process. Following cytostatic and radiation therapy, total regression of the tumour took place. The prognosis is considered favourable. The paper surveys the etiology of tumours of the posterior hard palate. PMID- 2243767 TI - A sensitive method for the determination of protein-DNA binding specificities. AB - We describe a sensitive and rapid method for determination of the sequence specificity of DNA binding proteins. The method allows recovery of specific sites using the small amounts of protein present in crude cell extracts or produced by cell-free translation reactions. Extract proteins are incubated with a pool of random sequence oligonucleotides, complexes purified by immunoprecipitation, and bound DNA amplified by the Polymerase Chain Reaction (PCR). This DNA is then used in further rounds of binding, immunoprecipitation, and amplification, until specific binding is detectable. With the transcription factor SRF as a model system, we demonstrate that authentic high affinity binding sites are recovered, and show that epitope tagging can be used to allow recovery of sites when specific antibodies are unavailable. We also show that specific sites bound by the Fos protein, which binds DNA with high affinity only when complexed with other polypeptides, are easily recovered by this technique. PMID- 2243768 TI - The rejoining of double-strand breaks in DNA by human cell extracts. AB - A double-strand DNA break was introduced at a specific site within the lacZ gene of plasmid pUC18 using one of several restriction enzymes, and the plasmid exposed to nuclear extracts from human cell lines. Physical rejoining of DNA was monitored by Southern analysis after gel separation, and the fidelity of rejoining by expression of the lacZ gene after bacterial transformation with the treated plasmid. Breaks at the SalI and EcoRI sites were rejoined by extracts to form circular monomers, but the efficiency of rejoining was much higher at the SalI site. Measurement of rejoining at several adjacent sites having different types of termini, consistently showed a range of efficiencies with 5' 4-base greater than 3' 4-base overhangs and 4-base greater than 2-base greater than no overhang. Similar efficiencies were found for nuclear extracts from transformed cell lines, both from a 'normal' individual and an ataxia-telangiectasia (A-T) patient, and from a non-transformed normal cell culture. In contrast at some sites, especially those with a low rejoin efficiency, the fidelity of rejoining was very much lower for the A-T extracts than for normal cell extracts. Mis rejoining was, however, unrelated to rejoin efficiency at other sites, suggesting that factors such as the exact sequence at the break site on the molecule may also influence the fidelity of rejoining. PMID- 2243769 TI - Size and physical map of the Campylobacter jejuni chromosome. AB - The chromosome of Campylobacter jejuni is circular and approximately 1700 kb in circumference. The size of the genome was determined by field inversion gel electrophoresis of restriction endonuclease fragments using lambda DNA concatamers and yeast chromosomes to calibrate the size of the fragments. In view of the low (32-35%) G + C content of the campylobacter genome, enzymes that recognizes GC-rich sequences were used. Of the enzymes tested BssHII (G/C(G)CGC), NciI (CC/CGCG) and SalI (G/TCGAC) appeared to be usable. Hybridization of labeled fragments with two or more fragments from digests with a different restriction enzyme gave the information to order the fragments on the C jejuni chromosome. The localization on the genome of the flagellin and ribosomal gene clusters was determined. PMID- 2243770 TI - Gene F of plasmid RSF1010 codes for a low-molecular-weight repressor protein that autoregulates expression of the repAC operon. AB - The repAC operon of plasmid RSF1010 consists of the genes for proteins E, F, RepA (DNA helicase), and RepC (origin-binding initiator protein) and is transcriptionally initiated by a promoter called P4. We have studied the expression of the repAC operon in vivo by using fusions to the lacZ reporter gene. The results show that the product of the second gene, F, autoregulates the operon by inhibiting transcription from P4. To verify its properties postulated from the in vivo studies and to initiate its biochemical characterization, we have purified the F protein from an overproducing E.coli strain constructed in vitro. Purification was based on a gel retardation assay for detection of P4 specific DNA binding. Subsequent DNase footprinting of the F binding sites showed clear protection around two partially symmetric P4 sequences of 16 bp, each of which matches the symmetric consensus sequence, GCGTGAGTACTCACGC, in at least 13 positions. The native repressor, as judged from gel filtration, velocity sedimentation and crosslinking studies, exists as a dimer in dilute solution; its monomeric subunit, as predicted from DNA sequence and N-terminal protein sequence data, consists of 68 amino acids and has a calculated M tau = 7,673. PMID- 2243771 TI - Human DNA polymerase alpha catalytic polypeptide binds ConA and RCA and contains a specific labile site in the N-terminus. AB - The catalytic polypeptide of DNA polymerase alpha is often observed in vitro as a family of phosphopolypeptides predominantly of 180 and 165 kDa derived from a single primary structure. The estimated Mr of this polypeptide deduced from the full-length cDNA is 165 kDa. Immunoblot analysis with polyclonal antibodies against peptides of the N- and C-termini of the deduced primary sequence indicates that the observed family of polypeptides from 180 kDa to lower molecular weight results from proteolytic cleavage from the N-terminus. Antibodies against the N-terminal peptide detect only the 180 kDa species suggesting that this higher molecular weight polypeptide may be the result of posttranslational modification of the 165 kDa primary translation product. The catalytic polypeptide is not only phosphorylated but is also found to react with lectins ConA and RCA. N-terminal sequencing of the isolated catalytic polypeptide from human cells and of the recombinant fusion proteins indicates that the often observed 165 kDa polypeptide is the in vitro proteolytic cleavage product of the modified 180 kDa protein at the specific site between lys123 and lys124 within the sequence -RNVKKLAVTKPNN-. PMID- 2243773 TI - Generation of small mutation in large genomic fragments by homologous recombination: description of the technique and examples of its use. AB - We have developed a technique of homologous recombination in bacteria which allows the mutagenesis of large genomic fragments cloned in cosmids. The desired mutation is first introduced into a plasmid clone and is then transferred to the appropriate cosmid clone by the means of double antibiotic selection coupled with phenotypic selection. We describe three different types of construct made by this technique. PMID- 2243774 TI - The signal for growth rate control and stringent sensitivity in E. coli is not restricted to a particular sequence motif within the promoter region. AB - Hybrid promoter constructs were used to determine the DNA sequence requirements for stringent and growth rate control within a promoter region. The promoters were obtained by fusing complementing sequence regions located upstream and downstream from the GCGC discriminator motif of the growth rate regulated rRNA P1 promoter and a non-regulated tac promoter variant. The activities and the regulatory response of the hybrid promoters were determined in vivo using a promoter test vector system with the chloramphenicol acetyltransferase (CAT) reporter gene. Measurements were made at different growth rates and after starvation for isoleucine to induce the stringent response. Neither the upstream nor the downstream sequence of P1 relative to the GCGC discriminator motif conferred comparable regulatory features when fused to the complementing sequences of the non-regulated mutant tac promoter. A minor response to amino acid deprivation or changes in the growth rate was noted for the hybrid promoter with the rrnB P1 upstream segment and the tac downstream element, pointing to a slightly different importance of the two sequence elements for regulation. The parallel effects for stringent as well as growth rate regulation of the hybrid promoters supports the view of a common mechanism for both types of control. However, none of the promoter sequence elements on its own was able to restore the complete regulatory behaviour of their 'parent' promoters. PMID- 2243772 TI - A highly conserved enhancer downstream of the human MLC1/3 locus is a target for multiple myogenic determination factors. AB - A potent muscle-specific enhancer element, originally described in the rat myosin light chain (MLC) 1/3 locus located downstream of the coding region, is found in an analogous position in the human MLC1/3 gene. When linked to a CAT reporter gene and transfected into muscle or non-muscle cells, the human MLC enhancer directs high levels of muscle-specific gene expression from homologous or heterologous promoters, irrespective of position or orientation relative to the CAT transcription unit. A significant degree of sequence homology (over 85%) in the 3'-flanking regions of the two MLC genes is restricted to a 200 bp sequence which lies approximately 1.5 kb downstream of the polyadenylation site in both species. The human enhancer sequence includes binding sites for human myogenic determination factors containing a common basic helix-loop-helix motif, and it can be trans-activated to varying degrees in non-muscle cells by these factors. This study establishes the MLC enhancer as an evolutionarily conserved, integral component of the MLC1/3 locus which constitutes a novel target for the action of myogenic determination factors. PMID- 2243775 TI - Drosophila RNA polymerase II elongation factor DmS-II has homology to mouse S-II and sequence similarity to yeast PPR2. AB - DmSII is a Drosophila RNA polymerase II elongation factor which suppresses pausing by RNA polymerase II at specific sites on double stranded templates. Using antibodies produced against the purified protein, a Drosophila cDNA expression library was screened and a cDNA was isolated which encoded a portion of DmSII. When this cDNA was used to probe Kc cell mRNA the predominant species was found to be 1.4 kb in length. The original cDNA was used to screen a Drosophila Kc cell cDNA library resulting in the isolation of a 1.4 kb cDNA which was then sequenced. The deduced protein sequence for DmSII exhibited high similarity to mouse SII protein sequence. In addition, significant sequence similarity was found with the protein encoded by the yeast gene PPR2, which is involved in regulation of URA4 gene expression. The comparison of amino acid sequences suggests that DmSII is comprised of two domains homologous to mouse SII separated by a flexible, serine rich region of low homology. The shorter yeast protein has sequence similarity only to the carboxy terminal domain. PMID- 2243776 TI - Field inversion gel electrophoresis with different pulse time ramps. AB - The influence of different pulse time ramps on the separation of yeast chromosomes with field inversion gel electrophoresis (FIGE) was investigated by the means of two dimensional gel electrophoresis. The problem of band inversion, which makes it difficult to distinguish DNA molecules of different size, has been solved by using double randomized pulse times. A major disadvantage of the field inversion technique is thereby overcome, making this system comparable to other pulsed field techniques. PMID- 2243777 TI - Fourier methods for biosequence analysis. AB - Novel methods are discussed for using fast Fourier transforms for DNA or protein sequence comparison. These methods are also intended as a contribution to the more general computer science problem of text search. These methods extend the capabilities of previous FFT methods and show that these methods are capable of considerable refinement. In particular, novel methods are given which (1) enable the detection of clusters of matching letters, (2) facilitate the insertion of gaps to enhance sequence similarity, and (3) accommodate to varying densities of letters in the input sequences. These methods use Fourier analysis in two distinct ways. (1) Fast Fourier transforms are used to facilitate rapid computation. (2) Fourier expansions are used to form an 'image' of the sequence comparison. PMID- 2243778 TI - Construction of a human chromosome 3 specific NotI linking library using a novel cloning procedure. AB - Two new diphasmid vectors (lambda SK17 and SK22) and a novel procedure to construct linking libraries are described. A partial filling-in reaction provides counter-selection against false linking clones in the library, and obviates the need for supF selection. The diphasmid vectors, in combination with the novel selection procedure, have been used to construct a chromosome 3 specific NotI linking library from a human chromosome 3/mouse microcell hybrid cell line. The application of the new vectors and the strong biochemical and biological selections resulted in a library of 60,000 NotI linking clones. As practically all of them are real NotI linking clones (no false recombinants) the library represents approximately 3,000 human recombinants (equal to 10-15 genomic equivalents of chromosome 3). Previously published methods for construction of linking libraries are compared with the procedure described in the present paper. The advantages of the new vectors and the novel protocol are discussed. PMID- 2243779 TI - On the movement and alignment of DNA during 120 degrees pulsed-field gel electrophoresis. AB - The displacement per pulse of lambda, T4, and G DNA during pulsed-field agarose gel electrophoresis has been measured for a fine mesh of pulse durations T between 0.02 and 120 s. The slopes of these curves show that the DNA moves by two distinct processes, designated 1 and 2, depending upon the pulse duration T. Process 1 operates at short T and causes dx/dT to decrease gradually with increasing T. This process is independent of molecular weight M. Process 2 is effective at longer T and causes dx/dT to rise sharply in sigmoidal fashion at a value of T which increases as M1.2, finally reaching a plateau of 1.4 microns/s for E = 4 V/cm. The shape of the dx/dT curve and its dependence on M lead directly to 4 zones of separation in plots of mobility vs M for different T. The alignment of the 3 DNAs during PFGE was measured by fluorescence-detected linear dichroism for E between 4 and 10 V/cm. These results are used in developing a molecular understanding of the mobility data. PMID- 2243780 TI - Circular dichroism studies of an oligodeoxyribonucleotide containing a hairpin loop made of a hexaethylene glycol chain: conformation and stability. AB - An oligodeoxyribonucleotide, d(GCTCACAAT-X-ATTGTGAGC), where X represents a hexaethylene glycol chain, was studied using circular dichroism spectroscopy. Its conformation and conformational stability were compared to those of compounds where X was replaced by four thymines and to the duplex of same sequence without loop. The compound with the hexaethylene glycol chain can form a hairpin looped structure as well as a bulged duplex structure. In both cases the duplex region of the oligodeoxyribonucleotide exhibits the same conformation. In similar conditions the oligodeoxyribonucleotide with a four thymines loop forms exclusively a hairpin structure. Comparison between the thermodynamic parameters (delta H, delta S, delta G) associated with the formation of the structure of the three compounds are presented. In the case of the compound with the hexaethylene glycol chain it is shown that the large increase in its melting temperature (by about 35 degrees C in our experimental conditions) when compared to the non looped structure is mainly due to the fact that its melting process is intramolecular (monomolecular) whereas the other one is bimolecular. PMID- 2243781 TI - The enhancers and promoters of the Xenopus laevis ribosomal spacer are associated with histones upon active transcription of the ribosomal genes. AB - The presence of histones on the enhancer-promoter region of the X.laevis ribosomal spacer has been studied in embryos at stage 40, where the ribosomal genes are actively transcribed. Isolated tadpole nuclei were either fixed with formaldehyde or irradiated with UV laser to crosslink histones to DNA. The purified protein-DNA complexes were immunoprecipitated with antibodies to the histones H1, H2A and H4 and the DNA fragments carrying the respective histones were analyzed for the presence of spacer enhancer-promoter sequences by hybridization to specific DNA probe. The two independent crosslinking procedures revealed the presence of these DNA sequences in the precipitated DNA. The quantitative analysis of the UV laser-crosslinked complexes showed that histones H2A and H4 were associated with enhancer-promoter DNA in amounts similar to those found for bulk DNA, whilst the content of H1 was reduced. PMID- 2243783 TI - Optimization of the annealing temperature for DNA amplification in vitro. AB - In the polymerase chain reaction (PCR) technique, DNA is amplified in vitro by a series of polymerization cycles consisting of three temperature-dependent steps: DNA denaturation, primer-template annealing, and DNA synthesis by a thermostable DNA polymerase. The purity and yield of the reaction products depend on several parameters, one of which is the annealing temperature (Ta). At both sub- and super-optimal Ta values, non-specific products may be formed, and the yield of products is reduced. Optimizing the Ta is especially critical when long products are synthesized or when total genomic DNA is the substrate for PCR. In this article we experimentally determine the optimal annealing temperature (TaOPT) values for several primer-template pairs and develop a method for its calculation. The TaOPT is found to be a function of the melting temperatures of the less stable primer-template pair and of the product. The fact that experimental and calculated TaOPT values agree to within 0.7 degree C eliminates the need for determining TaOPT experimentally. Synthesis of DNA fragments shorter than 1 kb is more efficient if a variable Ta is used, such that the Ta is higher in each consecutive cycle. PMID- 2243784 TI - Nucleotide sequence of rice dwarf virus genome segment 3. PMID- 2243785 TI - Nucleotide sequence of the Adh gene of Drosophila lebanonensis. PMID- 2243782 TI - Nuclease mapping and DNA sequence analysis of transcripts from the dihydrofolate reductase-thymidylate synthase (R) region of Leishmania major. AB - Trypanosomatid protozoan parasites utilize a number of nonstandard mechanisms in expressing their genes. To probe these phenomena in a genetically accessible system, we have mapped termini of eight transcripts arising from the amplified R region including the DHFR-TS gene of methotrexate-resistant Leishmania major. Poly(A)+ RNAs transcribed from the DHFR-TS-coding strand exhibit features similar to those observed around other trypanosomatid protein-coding genes. These include close spacing, the presence of a transpliced miniexon on the 5' termini, heterogeneity at both 5' and 3' ends, and in some cases S1 nuclease protection of intertranscript regions. Other than the splice acceptor site, no consensus sequence elements associated with either 5' or 3' ends were detected, although polydinucleotide tracts tended to be near inter-transcript regions. Two poly(A)+ RNAs transcribed from the opposite strand of the upstream flanking regions lacked the miniexon. Sequencing of DNA encoding the overlapping 1.7 kb opposite strand transcripts (one bearing and one lacking the miniexon, both found on polysomes) revealed no reading frames likely to encode proteins, suggesting that at least some of these RNAs could be nonfunctional by-products of RNA processing. PMID- 2243786 TI - Cloning and nucleotide sequence of a cDNA encoding the mink growth hormone. PMID- 2243787 TI - DNA sequence of the gene encoding the Zc1 protein from Zea mays W64 A. PMID- 2243788 TI - Sequence analysis of a genomic clone encoding a Zc2 protein from Zea mays W64 A. PMID- 2243789 TI - Nucleotide sequence of the genes encoding tRNA(his), tRNA(pro) and tRNA(gln) in the mitochondrial genome of Schizosaccharomyces pombe strain EF1. PMID- 2243790 TI - Nucleotide sequence of a porcine insulin-like growth factor II cDNA. PMID- 2243792 TI - Nucleotide and deduced amino acid sequences of chicken lactate dehydrogenase-A. PMID- 2243791 TI - Sequence of a lipase gene from the antarctic psychrotroph Moraxella TA144. PMID- 2243793 TI - Nucleotide sequence of the gene for a metalloproteinase inhibitor of Streptomyces nigrescens (SMPI). PMID- 2243794 TI - Complete nucleotide sequence of the PvuII restriction enzyme gene from Proteus vulgaris. PMID- 2243795 TI - Nucleotide sequence of the nodG gene of Azospirillum brasilense. PMID- 2243796 TI - DNA sequence of lipoprotein lipase cDNA cloned from human monocytic leukemia THP 1 cells. PMID- 2243797 TI - Nucleotide sequence of Coxiella burnetii superoxide dismutase. PMID- 2243798 TI - The sequence of the Kluyveromyces lactis BiP gene. PMID- 2243799 TI - Nucleotide sequence between the fadB gene and the rrnA operon from Escherichia coli. PMID- 2243800 TI - Nucleotide sequences of two genes CAH1 and CAH2 which encode carbonic anhydrase polypeptides in Chlamydomonas reinhardtii. PMID- 2243801 TI - The nucleotide sequence of greA, a suppressor gene that restores growth of an Escherichia coli RNA polymerase mutant at high temperature. PMID- 2243802 TI - Cloning, sequence and expression of rat cathepsin D. PMID- 2243803 TI - Nucleotide and amino acid sequences of the conidium-specific SpoC1-C1D gene from Aspergillus nidulans. PMID- 2243804 TI - The lumazine protein gene in Photobacterium phosphoreum is linked to the lux operon. PMID- 2243805 TI - Porcine growth hormone receptor cDNA sequence. PMID- 2243806 TI - Nucleotide sequences of psbB and psbH, the plastid encoded genes for CP47 and the 10 kDa phosphoprotein of photosystem II in Oenothera hookeri and argillicola. PMID- 2243807 TI - Cloning and sequence analysis of the cDNA for murine interleukin-6. PMID- 2243808 TI - cDNA sequence of a human heat shock protein HSP27. PMID- 2243809 TI - A novel protein (suef) programmed by the leftwards strand of a chimeric cDNA stops the expression of several proteins in E. coli. PMID- 2243810 TI - DNA polymers of protein binding sequences generated by PCR. PMID- 2243811 TI - Incorporation of multiple reporter groups on synthetic oligonucleotides. PMID- 2243812 TI - A rapid DNA isolation procedure from petri dish grown clinical bacterial isolates. PMID- 2243813 TI - Improved synthesis of full-length RNA probe at reduced incubation temperatures. PMID- 2243814 TI - New nucleotide sequence data on the EMBL File Server. PMID- 2243815 TI - [Predicting the incidence of malignant neoplasms in Cracow in the year 2000]. AB - In connection with the data of the Cracov Tumor Registry concerning the 1970-1985 period and the population prognoses of the city of Cracov the expected incidence and the number of patients with most common malignant neoplasms in the year 2000 has been estimated. One can foresee the continuance of the decrease of the risk and incidence of malignant neoplasms of the stomach in both sexes and of cancer of the lung and breast in women. The incidence of malignant neoplasms in general as compared with the year 1985 will in the year 2000 increase by ca. 60% in men and by ca. 39% in women. PMID- 2243816 TI - [Malignant lymphoma (non-Hodgkin's)--principles of oncological management]. AB - Principles of diagnostic and therapeutic management of malignant lymphoma patients have been presented, accounting for a variety of histologic types, clinical staging, and risk factors. The role of chemotherapy, radiotherapy, and surgery has been outlined up to the range necessary for planning of combined treatment of diverse clinical types of lymphomas. PMID- 2243818 TI - Montpellier Cancer Institute strategy and experience in surgical treatment of multi-bilateral hepatic metastases from digestive tract cancers. AB - Montpellier Cancer Institute strategy and experience in surgical treatment of multi-bilateral hepatic metastases from digestive tract cancers is presented based on retrospective case by case analysis of survival time of 38 patients. The mean age was 46.2 years and the primaries were colorectal (22 patients) and endocrine (16 patients). Liver surgery was synchronous to the resection of primary lesions in 8 patients and metachronous in 22 patients. Two-step liver surgery was performed in 8 patients. Overall thirty-days postoperative mortality was 7.8% and morbidity 15.7% (wound sepsis, subphrenic abscess, transitory jaundice, biliary fistula). The analysis of survival time evidenced that with reasonable risk-benefit ratio the aggressive surgical approach can be justified especially in patients with endocrine primaries. PMID- 2243817 TI - [Chronochemotherapy of neoplasms]. AB - The problems of chronobiology in chemotherapy are discussed in connection with experimental and clinical experience. Special attention is payed to selected from most commonly applied cytostatics cis-platinum and doxorubicin, their toxicity in different hours of the day and efficacy in treatment of malignant neoplasms in human. PMID- 2243819 TI - [Sacrectomy at the level of S2 in schwannoma of the sacral region. Case report and review of the literature]. AB - Rare case of highly differentiated malignant Schwannoma of the sacral region is described. The patient, a 30 year old woman, underwent sacrectomy at the level of S2. Postoperative course was uneventful. She has lived more than two years without any complaints or signs of disease. Technical details of surgical procedure are presented and discussed. PMID- 2243820 TI - [Evaluation of the experimental program of teaching about neoplasms in Warsaw schools]. AB - The study was to test the cancer education curriculum offered by teachers in 3 types of schools in Warsaw. The knowledge of cancer grew by 6% in the experimental schools and by 2% in control schools. Similar results were obtained in schools of Lodz, where the subject was also taught by teachers. A considerable greater knowledge increase, by 27% on the average, was obtained in schools of Lublin, where the subject was taught by professional oncologist. This seems to indicate still insufficient qualification of school teachers as regards teaching about cancer, despite a handbook on the subject which has been prepared for them. PMID- 2243821 TI - Bronchoscopy in critically ill patients. When is it appropriate? AB - Fiberoptic bronchoscopy is a valuable diagnostic and therapeutic tool for use in carefully selected patients with serious pulmonary disease. The authors review the benefits and risks of fiberoptic bronchoscopy and discuss the essentials of nursing care before, during, and after the procedure. PMID- 2243823 TI - The persistent vegetative state. PMID- 2243822 TI - Repetitive strain injuries. How to deal with 'the epidemic of the 1990s'. AB - Occupational trends, especially the mushrooming of computer use in the United States, have brought with them a virtual epidemic of repetitive strain injury of the upper limb. What can you as a primary care physician do to stem the tide? In this article, the authors fill you in on treatment of the most common injuries as well as remark on the ramifications for business and industry. PMID- 2243824 TI - Evaluating hematuria in children. Where to start and how to proceed. AB - Bleeding from somewhere along the urinary tract is not unusual in children. Of the many causes, systemic infection and trauma are among the most common. History taking and physical examination should be careful and complete, because the results obtained help direct the laboratory evaluation. Diagnostic testing always begins with urinalysis but may progress to intravenous urography, voiding cystourethrography, endoscopic procedures in the upper and lower urinary tract, sonography, arteriography, or renal biopsy. Some cases remain unexplained and require follow-up to assess renal function. PMID- 2243825 TI - And you think you have it bad? Try $360 a month! PMID- 2243826 TI - Operation Desert Shield.